Podcasts about Angiotensin

N Engl J Med 2001;345:494-502.Background The established medical treatments for acute coronary syndrome reviewed so far include aspirin and thrombolytics along with a smaller role for short-term anticoagulation. Angiotensin converting enzymes inhibitors and, to a lesser extent, beta blockers were also found to reduce recurrent ischemic events and death as well as heart failure and ventricular remodeling. The EPHESUS trial, which studied Eplerenone in this patient population was not published until several years later.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Despite the benefits of the above therapies, patients who experienced an ACS event were still at a substantially higher risk for experiencing recurrent events compared to patients who never experienced an ACS event. Significant interest remained in finding additional agents to reduce “residual risk” (i.e., the risk of recurrent events that is left over after initiating effective therapies). Imagine a heart attack survivor has a 20% risk of experiencing death, non-fatal MI or heart failure over the next 5 years. Now imagine that all known effective therapies cumulatively reduce that risk by 30% (a 6% absolute reduction in risk); the residual risk for events over 5 years would still be 14%, which is still high, and significantly higher than patients who never experienced an ACS event (e.g., primary prevention patients).Thienopyridine derivatives, including clopidogrel, are antiplatelet agents with a different mechanism of action than aspirin. Up to this point in time they demonstrated efficacy in patients who had received a coronary stent for reducing myocardial infarction compared to either aspirin alone or warfarin. The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial sought to test the hypothesis that 3 to 12 months of clopidogrel plus aspirin versus aspirin alone would reduce the rate of cardiovascular events (a composite endpoint) compared to aspirin alone in patients with ACS and no ST-segment elevation.Patients Patients were eligible if they had been hospitalized within 24 hours after the onset of symptoms, who had either ECG changes or an elevation in cardiac enzymes at entry, and did not have ST-segment elevation. Exclusion criteria included a contraindication to antithrombotic or antiplatelet therapy, high bleeding risk or severe heart failure, those who were taking oral anticoagulants, and those who had undergone coronary revascularization in the previous 3 months or had received intravenous glycoprotein IIb/IIIa receptor inhibitors in the previous 3 days.Baseline characteristics No information in the main manuscript is provided on the ratio of patients eligible to those enrolled, which limits our ability to make inferences about external validity. The average age of participants was 64 years of age and nearly 40% were woman, which is historically higher than the trials reviewed up to this point. The average time from pain onset to randomization was 14 hours. The diagnoses at study entry were unstable angina in 75% and MI in 25%. Many patients in the trial has a history of MI (32%) or revascularization (18%) in the past and the majority were either current or former smokers (61%). Most patients (94%) had some ECG abnormality; the most common being ST depression (42%) and T-wave inversion (36%).Procedures Immediately following randomization patients were administered a 300 mg loading dose of clopidogrel or matching placebo followed by 75 mg per day of clopidogrel or matching placebo for 3 to 12 months (the mean duration of treatment was 9 months). Aspirin was started or continued simultaneously with the study drug or placebo. Follow-up assessments occurred at discharge, at 1 and 3 months, and then every 3 months until the end of the study (12 months).Endpoints The first primary endpoint was the composite of death from cardiovascular causes (death for which there was no clearly documented nonvascular cause), nonfatal MI (which required at least 2 of 3 findings: ischemic chest pain, elevation of cardiac markers or ECG changes consistent with MI) or stroke (new focal neurological deficit of vascular origin lasting >24 hr and was subdivided into intracranial hemorrhage, ischemia, or uncertain cause) at 12 months. The second primary endpoint was the composite of the first primary endpoint or refractory ischemia. Secondary outcomes included severe ischemia, heart failure, and the need for revascularization. Safety related outcomes included life-threatening, major bleeding (requiring transfusion of ≥2 units of blood) or all other bleeding.The study was initially designed to include 9000 patients, with an anticipated primary event rate of 12-14% in the placebo group; however, because the event rate was lower than anticipated, the size of the study was increased as the trial was ongoing, with an adjusted rate of 10% in the placebo group. A final sample size of 12,500 patients was based on an anticipated 17% risk reduction for the primary composite endpoint with 90% power and a two-sided alpha level of 0.045.Results 12,562 patients were included in the final analysis; 6,303 in the placebo group and 6,259 in the clopidogrel group. During the initial hospital stay, 21% of patients in the clopidogrel group and 23% of patients in the placebo group underwent revascularization. At 1-year clopidogrel significantly reduced the occurrence of the first primary composite endpoint (RR 0.80; 9.3% vs 11.4%; 95% CI 0.72-0.90) and second primary composite endpoint (RR 0.86; 16.5% vs 18.8%; 95% CI 0.79-0.94). These differences were driven primarily by reducing nonfatal MI (RR 0.77; 5.2% vs 6.7%; 95% CI 0.0.67-0.89). There were no significant differences in death from cardiovascular or non-cardiovascular causes, stroke or refractory ischemia.Compared to placebo, clopidogrel significantly increased major bleeding (RR 1.38; 3.7% vs 2.7%; 95% CI 1.13-1.67). However, there was no significant excess of major bleeding in patients undergoing CABG surgery (RR 1.48; 1.3% vs 1.1%; 95% CI 0.93-1.71). The median time for clopidogrel discontinuation before CABG surgery was 5 days.Results from various subgroups are presented for the first primary composite endpoint and suggest the possibility of important treatment effect heterogeneity. Patients with a history of revascularization represented a minority of patients in the study (18%) and experienced higher rates of events but derived a significantly greater benefit from clopidogrel compared to those not previously revascularized (RR 0.58 vs 0.89).Patients >65 years of age made up about half of study participants, and experienced event rates >2x higher than those ≤65 years of age, but derived less benefit from clopidogrel (RR 0.87 vs 0.71). The same was true based on risk tertiles. Patients at low and intermediate risk of experiencing events based on risk scores, experienced similar risk reductions from clopidogrel of 76% and 69% respectively; however, those at the highest risk received less benefit (RR 91%). Finally, women appeared to benefit less than men (RR 89% vs 76%).Notably, there was no evidence of treatment effect heterogeneity based on whether patients underwent revascularization or not following randomization.During the trial, clopidogrel was discontinued temporarily (≥5 days) in 46% of patients mainly due to the need for a surgical procedure. A total of 21% of patients discontinued clopidogrel permanently compared to 18% in the placebo group.Conclusions In patients admitted to the hospital for unstable angina or NSTEMI, clopidogrel for 3-12 months plus aspirin, reduced the rate of a composite primary endpoint compared to aspirin alone and was associated with a number needed to treat of approximately 50 patients. This benefit was driven almost entirely by reducing nonfatal MI. Clopidogrel increased major bleeding with an NNH of approximately 100 patients.In our opinion, the benefit conferred by clopidogrel in this patient population is modest and the external validity is uncertain as no information is provided on patients enrolled compared to those who were eligible/screened. Patients with prior histories of revascularization derived the greatest benefit; however, several higher risk subgroups including older patients (>65 years of age) and the third of patients who were at the highest risk of experiencing events derived significantly less benefit. Women, also derived less benefit. In the groups less likely to benefit, we would expect them to experience higher rates of adverse events as well and thus, it is possible they derive no net benefit from clopidogrel or could even experience net harm.While thienopyridines have come to be considered a foundational treatment for ACS, evidence of their benefit from the CURE trial is modest at best; based mainly on reduction of a nonfatal endpoint.The CURE trial results should be translated cautiously, especially for patients who are older, frail and more susceptible to adverse events.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Commentary by Dr. Valentin Fuster

Dr. Briggs and Brendon Neuen discuss his paper in the December issue of JASN. This article on the CREDENCE and EMPA-CKD clinical trials shows that SGLT2 inhibitors allow more consistent use of RAS blockade in patients with declining renal function.

Commentary by Dr. Valentin Fuster

The following episode provides part one of sodium physiology examining how the body regulates sodium levels via the renin-angiotensin-aldosterone system.    One of my favorite lectures on this topic: https://www.youtube.com/watch?v=NMWaKdO76NQ    

⁠DozeNews PRIME⁠⁠⁠⁠: as melhores e mais didáticas revisões de cardiologia direto na sua caixa de entrada! Assine agora e tenha acesso à todo material já produzido! - ⁠⁠⁠⁠https://dozeporoito.substack.com Continuamos com o sarrafo alto!  A parceria Doze Por Oito Cardiologia e o 81º Curso Intensivo do Dante Pazzanese continua e, dessa vez, Rapha Rossi e William Batah contam com o retorno de nossa querida convidada e especialista em disfunção ventricular, Dra. Carolina Casadei para debater as principais nuances do uso das duas novas principais medicações no tratamento da insuficiência cardíaca: os INRAs e I-SGLT2. Esse episódio tem apoio do Insituto Dante Pazzanese de Cardiologia ⏱️ Minutagem: (00:00) Apresentação (02:20) Quem são e quando usar os INRAs? (08:30) Como iniciar o INRA? (12:50) Quando nao usar os INRAs (17:15) Qual o papel dos INRAs na ICFEP (20:00) Porque usar os I-SGLT2 (27:00) Como funcionam os I-SGLT2 e quando usar? (33:00) Dapagifozina na ICFEP (37:20) Cuidados ao usar I-SGLT2 (42:00) Considerações finais Referências: McMurray JJ, et al ; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. doi: 10.1056/NEJMoa1409077. Epub 2014 Aug 30. PMID: 25176015. Packer M,et al; EMPEROR-Reduced Trial Investigators. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020 Oct 8;383(15):1413-1424. doi: 10.1056/NEJMoa2022190. Epub 2020 Aug 28. PMID: 32865377. Solomon SD, et al. Dapagliflozin in heart failure with preserved and mildly reduced ejection fraction: rationale and design of the DELIVER trial. Eur J Heart Fail. 2021 Jul;23(7):1217-1225. doi: 10.1002/ejhf.2249. Epub 2021 Jun 9. PMID: 34051124; PMCID: PMC8361994.

You probably know that the kidneys play an important role in maintaining blood pressure within the normal range. You might also know that they do this by regulating blood volume and the degree of arterial contraction or dilation (the systemic vascular resistance). But do you know how the kidneys do this? The answer is the kidneys accomplish this primarily through a set of hormones and enzymes known together as the renin-angiotensin-aldosterone system (RAAS). In this brick, we will discuss the components, functions, and regulation of the RAAS. Renin is an enzyme released by the kidneys that ultimately causes the formation of the hormone angiotensin II (Ang II) in the body—which in turn stimulates the release of the hormone aldosterone from the adrenal cortex. Ang II and aldosterone act in a number of ways to increase blood volume and blood pressure. RAAS acts to increase sodium reabsorption in the kidney, increase vascular tone, and even stimulate antidiuretic hormone (ADH) to reabsorb more water: all of these defend our extracellular volume and blood pressure. RAAS is therefore a critical system for keeping us upright! After listening to this Audio Brick, you should be able to: Outline the renin-angiotensin-aldosterone system, including sensors, factors that control it, sources of hormone release, and the actions of each hormone. Describe the mechanisms by which the renin-angiotensin-aldosterone system regulates blood pressure. Compare and contrast tubuloglomerular feedback with the renin-angiotensin-aldosterone system. You can also check out the original brick from our Endocrine collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks.  After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology. *** If you enjoyed this episode, we'd love for you to leave a review on Apple Podcasts.  It helps with our visibility, and the more med students (or future med students) listen to the podcast, the more we can provide to the future physicians of the world. Follow USMLE-Rx at: Facebook: www.facebook.com/usmlerx Blog: www.firstaidteam.com Twitter: https://twitter.com/firstaidteam Instagram: https://www.instagram.com/firstaidteam/ YouTube: www.youtube.com/USMLERX Learn how you can access over 150 of our bricks for FREE: https://usmlerx.wpengine.com/free-bricks/ from our Musculoskeletal, Skin, and Connective Tissue collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks.  After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology.

Editor's Summary by Kirsten Bibbins-Domingo, PhD, MD, MAS, Editor in Chief of JAMA, the Journal of the American Medical Association, for the April 11, 2023, issue. Related Content: Audio Highlights

The second of the RAAS system blockers! Very similar to the ACE Inhibitors with a little twist. "And all the Sartans assembled........."

In this extremely HY podcast, I discuss the renin angiotensin aldosterone system in detail and also make lots of integrations that show up as exam questions on all the USMLEs. Definitely worth a listen before you take your test. Audio Download

Here we are with the ACE Inhibitors!! Yet another versatile class of drugs and oh how smart those scientists were to discover them. Listen up.

In dieser Folge nehmen wir das RAAS unter die Lupe. Wir klären, wie es genau abläuft und welche Hormone zum Einsatz kommen.

This week we're thrilled to speak with one of the busiest (and most wonderful) scientists we know: Associate Professor Francine Marques. Francine is a Viertel Charitable Foundation and National Heart Foundation Fellow, and head of the Hypertension Research Laboratory at Monash University. She has published >90 peer-reviewed papers in top journals such as Nature Reviews Cardiology, Nature Medicine and Circulation, and has secured $7 million in competitive funding. Francine has won 25 awards including the 2019 American Heart Association Hypertension Council Goldblatt Award, 2020 High Blood Pressure Research Council of Australia and 2021 International Society of Hypertension Mid-Career Awards, and the 2021 Australian Academy of Science Gottschalk Medal. Her team investigates the molecular mechanisms behind the development of high blood pressure, with a focus on disease identification and prevention via the gut microbiota using both animal studies and clinical trials. Francine is also the co-program manager for the High Blood Pressure Research Council of Australia, the chair of the International Society of Hypertension Mentoring and Training Committee, and an elected member of the steering committee for the Gordon Research Conference on Angiotensin. Francine is an amazing science communicator and is passionate about effective and compassionate leadership in science – you can read her lab manual which we discussed here: https://www.marqueslab.com/manual. You call follow Francine and find out more about her work here: https://twitter.com/fzmarques https://www.monash.edu/science/schools/biological-sciences/staff/francine-marques https://www.marqueslab.com/ https://womensagenda.com.au/leadership/associate-professor-francine-marques-on-leading-landmark-blood-pressure-research/ https://cosmosmagazine.com/science/biology/cancer-diagnosis-shaped-mindset/ Transcript: https://go.unimelb.edu.au/74pe

Patrick M. Wieruszewski, PharmD, BCCCP, describes the mechanisms of the renin-angiotensin system and its interplay in vasodilatory shock, reviews emerging data surrounding the use of angiotensin II in vasodilatory shock and identifies clinical shock scenarios where angiotensin II may be of most benefit.  For more pharmacy content, follow Mayo Clinic Pharmacy Residency Programs @MayoPharmRes or the host, Garrett E. Schramm, Pharm.D., @garrett_schramm on Twitter! You can also connect with the Mayo Clinic's School of Continuous Professional Development online at https://ce.mayo.edu/ or on Twitter @MayoMedEd. 

Heart failure patients are generally multi-morbid and at risk for hyperkalemia, which makes treatment with life-saving therapies like RAASi difficult and leads to compromised medical treatment and in turn poor outcomes. This trials showed that with the use of patiromer, one can simultaneously lower the risk of hyperkalemia and increase optimal medical therapy for heart failure with reduced ejection fraction. In this interview, Javed Butler, MD MPH MBA, Anthony N. DeMaria MD, MACC, with Ioannis Mastoris, MD, MPHcand, discuss the Late Breaker: DIAMOND trial: Patiromer For The Management Of Hyperkalemia In Subjects Receiving Renin-angiotensin-aldosterone System Inhibitor Medications For Heart Failure With Reduced Ejection Fraction.

Dr. Antony A. Boucard Jr. on the web Website LinkedIn Researchgate Loop Academia Pubmed Adhesion GPCR Consortium University of Haiti For more details, visit #DrGPCR Podcast Episode #66 page https://www.drgpcr.com/episode-66-with-antony-a-boucard-jr/ ------------------------------------------- About Dr. Antony A. Boucard Jr. Dr. Antony Boucard joined the Université de Sherbrooke (Québec, Canada) as a B.S. student of the Biochemistry program in 1994 from which he graduated in 1997. It is then that his interest bloomed for the study of GPCRs while joining the group of Dr. Richard Leduc and Dr. Gaetan Guillemette in the Pharmacology department at the Université de Sherbrooke. He completed a master's degree in 2000 and a Ph.D. degree in 2003 with a particular interest in the cardiovascular system by investigating the structure of the Angiotensin and Urotensin receptors through various biochemical approaches centered in the elucidation of ligand binding pocket determinants... Dr. Antony A. Boucard Jr. on the web Website LinkedIn Researchgate Loop Academia Pubmed Adhesion GPCR Consortium University of Haiti ------------------------------------------- We aspire to provide opportunities to connect, share, form trusting partnerships, grow, and thrive together. Fill out the Ecosystem waitlist form today to be the first to explore our brand new and improved space! For more details, visit our website http://www.DrGPCR.com/Ecosystem/.

In this episode, we review the high-yield topic of Renin-Angiotensin-Aldosterone System from the Renal section. Follow Medbullets on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbulletsIn this episode --- Send in a voice message: https://anchor.fm/medbulletsstep1/message

Iago Rodríguez-Lago talks to Neil O'Morain (Galway, Ireland) about his research about the effect of angiotensin receptor blockers in patients on a gluten-free diet.

Thanks for listening! In this episode Stan deep dives into the physiology of oliguria, with some great structures and mnemonics to really help learn this interesting but challenging topic!Here are some of the mentioned resourcesThe Covid 19 intubation video!https://youtu.be/uqKnuVfZoOgThe fantastic course by the Center for Medical Simulationhttps://harvardmedsim.orgPlease support us on our Patreonhttps://www.patreon.com/anaesthesiaAll proceeds will go to Fund a Fellow to help train anaesthetists in developing countries whilst acknowledging the work it takes to keep creating this educational resource.If you enjoyed this content please like and subscribePlease post any comments or questions below. Check out www.anaesthesiacollective.com and sign up to the ABCs of Anaesthesia facebook group for other content.Any questions please email lahiruandstan@gmail.comDisclaimer: The information contained in this video/audio/graphic is for medical practitioner education only. It is not and will not be relevant for the general public.Where applicable patients have given written informed consent to the use of their images in video/photography and aware that it will be published online and visible by medical practitioners and the general public.This contains general information about medical conditions and treatments. The information is not advice and should not be treated as such. The medical information is provided “as is” without any representations or warranties, express or implied. The presenter makes no representations or warranties in relation to the medical information on this video. You must not rely on the information as an alternative to assessing and managing your patient with your treating team and consultant. You should seek your own advice from your medical practitioner in relation to any of the topics discussed in this episode' Medical information can change rapidly, and the author/s make all reasonable attempts to provide accurate information at the time of filming. There is no guarantee that the information will be accurate at the time of viewingThe information provided is within the scope of a specialist anaesthetist (FANZCA) working in Australia.The information presented here does not represent the views of any hospital or ANZCA.These videos are solely for training and education of medical practitioners, and are not an advertisement. They were not sponsored and offer no discounts, gifts or other inducements. This disclaimer was created based on a Contractology template available at http://www.contractology.com.

In Folge 26 unserer Wissensreise lernen wir Medikamente kennen, die bei Herzerkrankungen gegeben werden. Themen sind: ACE-Hemmer, Renin-Angiotensin-Aldosteron-System, Sartane, Aldosteron-Antagonisten und Betablocker. Kurzfassungen gibt es in der nächsten Folge, da diese einfach zu lang geworden wäre. Viel Spaß beim Zuhören und Lernen ;-) Schreib mir gerne Anregung, Kritik oder einfach nur ein Hallo, auch an die Adresse: tanjaloiblhp@gmail.com. Hier kannst du mich und den Podcast unterstützen: https://steadyhq.com/wissensreise

On this ID the Future, physician Howard Glicksman and host Eric Anderson dive deeper into the body's exquisite blood pressure control system, cueing off a new discovery described at Science Daily as uncovering “the location of natural blood-pressure barometers inside our bodies that have eluded scientists for more than 60 years.” According to the primary research paper at Circulation Research, “Renin-expressing cells are essential for survival, perfected throughout evolution to maintain blood pressure (BP) and fluid-electrolyte homeostasis.” How did evolution perfect the system? How did it originate the system? The paper never says. The mention of evolution appears to be little more than a de rigueur genuflection before the reigning paradigm of blind evolution. What is bearing actual fruit, according to Glicksman Read More › Source

CoQ10 supplementation associated with improved trauma patient outcomes Urmia University of Medical Sciences (Iran) July 23 2021.    Findings from a trial reported on July 12, 2021 in the Journal of Nutritional Science revealed benefits for hospitalized traumapatients who were given supplements that contained coenzyme Q10.  The trial enrolled 40 men and women with traumatic injury and low plasma levels of CoQ10. Participants received a placebo or 400 milligrams CoQ10 daily for seven days. Blood samples collected at the beginning and end of the trial were analyzed for interleukin 6 (IL-6), which may be elevated during inflammation, and the oxidative stress markers malondialdehyde (MDA) and thiobarbituric acid reactive substances (TBARS). Body composition was also assessed at these time points, as well secondary outcomes that included Sequential Organ Failure Assessment (SOFA) and the Glasgow Coma Scale (GCS).  While interleukin-6 levels at the beginning of the study were similar between the CoQ10 and placebo groups at an average of 175.05 pg/mL and 177.82 pg/mL, they were reduced by 76.99 pg/mL in the CoQ10 group and 17.35 pg/mL in the placebo group. MDA values averaged 232.37 picograms per milliliter (pg/mL) and 239.96 pg/mL and were lowered by 88.84 pg/ml among participants who received CoQ10 and by 26.23 pg/mL among those who received a placebo. In comparison with the placebo group, fat free mass, skeletal muscle mass and body cell mass increased among those who received CoQ10. GCS and SOFA scores, and duration of hospital stay, ICU stay and ventilator use also improved among treated patients.  “To date, no randomized clinical trial study has been conducted to evaluate the effect of CoQ10 supplementation in traumatic mechanical ventilated patients and we hypothesized that CoQ10 administration in these patients could have beneficial effects on biochemical and clinical factors,” the authors wrote. “We have shown that CoQ10 could improve some of the clinical and anthropometric parameters in patients with a traumatic injury.”     Nigella sativa (black seed) prevents covid-induced vascular damage, scientists conclude   Oriental Institute of Science and Technology (India), July 27, 2021 New research published in the journal Vascular Pharmacology shows that Nigella sativa, also known as black seed or black cumin, binds to ACE2 in the lungs, effectively stopping the Wuhan coronavirus (Covid-19) from inducing inflammation and vascular damage. Researchers out of India investigated the effects of nigellidine, an indazole alkaloid of black seed, using molecular docking for binding to different angiotensin-binding proteins, as well as the Chinese Virus spike glycoprotein. They found that nigellidine “strongly binds” to the Chinese Virus spike protein at what is known as the hinge region or active site opening, which may in turn hamper its binding to the nCoV2-ACE2 surface. “Nigellidine effectively binds in the Angiotensin-II binding site / entry pocket,” the study explains. “Nigellidine showed strong binding to mono / multi-meric ACE1.” This process of ACE blocking could, the study goes on to suggest, restore angiotensin levels and restrict vasoturbulence in Chinese Virus patients, while the receptor blocking could help to stop resulting inflammation and vascular impairment. “Nigellidine may slow down the vaso-fluctuations due to Angiotensin deregulations in Covid patients,” the paper further explains. “Angiotensin II-ACE2 binding (ACE-value -294.81) is more favorable than nigellidine-ACE2. Conversely, nigellidine-ACE1 binding-energy / Ki is lower than nigellidine-ACE2 values indicating a balanced-state between constriction-dilatation.” Nigellidine also binds to the viral spike proteins, which when taken by Chinese Virus patients, and especially those who fall in the elderly category, could greatly reduce their risk of suffering complications or death. Nigellidine impairs SARS-CoV-2 infection, “cytokine storm” through numerous mechanisms In a related study that was published last year in the journal Europe PMC, researchers learned that nigellidine inhibits the Chinese Virus infection in several other ways. It was discovered early on in the “pandemic” that many of those who tested “positive” for the virus were suffering associated “cytokine storms,” in which their immune systems were over-responding and causing more damage, or even death. Nigellidine was then studied and discovered to possess certain properties that inhibit cytokine storms, as well as impede the SARS CoV-2 virus from causing infection. It is also hepato- and reno-protective, meaning it protects against liver damage. Beyond this, nigellidine was determined to possess unique immunomodulatory and anti-inflammatory characteristics, as well as antioxidant potential strong enough to inhibit important proteins associated with the Chinese Virus. In their quest to uncover possible “drug” candidates to protect patients against hyper-inflammation and other associated problems, the researchers learned that nigellidine – and more than likely other black seed constituents – helps tremendously with preventing negative side effects. Along with nigellicine, nigellidine is found in the seed coat of Nigella sativa. Both of these constituents in their sulfated forms are extremely bioavailable, and along with thymoquinone and dithymoquinone, two other black seed components, they show strong antioxidant, antibacterial, anti-hypertensive, anti-inflammatory and immunomodulatory effects. Black seed extracts have been shown in other experiments to decrease oxidative stress, effectively lowering the risk of inflammation-related diseases. We now know that this includes the Wuhan coronavirus (Covid-19). Black seed is also recognized as a metabolic protector, helping to improve lipid and blood sugar levels. “Most importantly, in SARS CoV-2 infection ACE-2 mediated impairment of aldosterone system may be repaired by,” the study further explains, providing relevant information to the current “pandemic.” “Vasorelaxant and anti-hypertensive function of [black seed] helps in the modulation of renin angiotensin system (RAS) or the diuretic activity, which is one of the major targets of COVID. It might have great protective role during post infective secondary disorder of the peripheral vasculature namely cardiac and renal systems. In most of the instances patients die due to this organ dysfunction/failure in COVID-19 infection.” By quelling inflammation, black seed could save lives from covid Laboratory studies have found that intake of Nigella sativa significantly improves the parameters for hyperglycemia and diabetes control, as well as glycated hemoglobin and insulin resistance. Based on this, experts believe that nigellidine specifically could play an important role in fighting the Chinese Virus by “docking” to the proteins and inflammatory molecules that can cause a cytokine storm – mainly TNF-? receptors such as TNFR1, TNFR2 and IL1R. “In the experimental rat model the source of this drug Nigella sativa; black cumin seed extracts were tested for its role on antioxidant, hepatic and renal status,” the paper states. “This work will help in the urgent therapeutic intervention against COVID-19 global pandemic.” “In the current study, we have decisively shown by molecular modeling that nigellidine can bind in the active sites of several important proteins of SARS CoV 2, several host receptors specific for SARS CoV-2 induced inflammatory markers IL1, IL6, TNF-?. Moreover, the extract from black cumin seed has been shown in experimental rat to be highly antioxidative, hepato- and reno-protective. Further studies are necessary to verify the potential effects of nigellidine in in vivo laboratory experimental animal model.”   Vitamin D supplementation improves recovery time of children with pneumonia at pediatric hospital Cairo University (Egypt), July 20, 2021 According to news reporting originating from Cairo, Egypt, by NewsRx correspondents, research stated, “Despite the well-recognized effect of vitamin D in metabolism and homeostasis, there is now growing interest in its probable association with pneumonia. This study aims to supply vitamin D3 (Cholecalciferol) (100,000 IU) to pneumonic children to minimize the duration of illness and improve their outcome.” Our news editors obtained a quote from the research from Cairo University, “A double-blinded, randomized, placebo-controlled trial was conducted in a Pediatric Cairo University affiliated hospital. An intervention arm (93 children) and a control arm (98 children), who had pneumonia with an insufficient or deficient level of vitamin D and whose parental permission was obtained, were enrolled in the trial. All children were treated with antibiotics according to WHO guidelines. Children were given a single injection of 1 mL of 100,000 IU of vitamin D3 or placebo. Clinical data were recorded every eight hours for all children. Outcomes were assessed 7 days after vitamin D injection. The primary outcome variable was the change in serum level of 25(OH)D, while the secondary outcomes were the medical state of the assigned cases (improvement or death) and duration between enrollment and hospital discharge for improved cases. In the supplementation group, the percentage of patients who suffered either deficient (38.7%) or insufficient levels (61.3%) of 25 (OH)D at day one had significantly decreased in the seventh day to (11.8%) and (52.7%), respectively. Kaplan--Meier plots highlighted that the median time to recover of the placebo group was significantly longer than that of the supplementation group (Log Rank P value < .001). VDD was detected in pediatric critical care children.” According to the news editors, the research concluded: “In pneumonic children with high VDD, it is illustrated that Vitamin D supplementation is accompanied by lowered mortality risk and pSOFA scores, reduced time to recover, and improved PaO2/FiO(2).”   Physical activity could combat fatigue, cognitive decline in cancer survivors University of Illinois, July 26, 2021 A new study indicates that cancer patients and survivors have a ready weapon against fatigue and "chemo brain": a brisk walk. Researchers at the University of Illinois, along with collaborators at Digital Artefacts in Iowa City, Iowa, and Northeastern University in Boston, looked at the association between physical activity, fatigue and performance on cognitive tasks in nearly 300 breast cancer survivors. "The data suggest that being more physically active could reduce two of the more commonly reported symptoms in breast cancer survivors: fatigue and cognitive impairment," said study leader Edward McAuley, a professor of kinesiology and community health at Illinois. "Most people think, 'If I exercise, I'll become tired.' In our study, exercise actually was associated with reduced fatigue, which in turn was associated with better cognitive function." Cognitive impairment, such as memory problems or shortened attention spans, is a common complaint among cancer patients and survivors, and is thought to be similar to decline due to aging. Past Illinois research has explored the effect of physical fitness on age-related cognitive decline, so the researchers wondered whether cancer survivors would respond similarly to exercise. "Other studies of cancer survivors have relied on small samples of cancer survivors, and used self-reporting measures of physical activity and cognitive function, which can be very biased," said postdoctoral researcher Diane Ehlers, the first author of the study, which is published in the journal Breast Cancer Research and Treatment. "What makes our study novel is that we had objective measures for both physical activity and cognitive performance, and a nationwide sample of breast cancer survivors." The researchers worked with Digital Artefacts -- developer of the commercial neuroscience app BrainBaseline - to create an iPad app tailored to this study. The app included questionnaires and activities designed to measure attention, memory and multitasking skills. The researchers also sent each participant an accelerometer to track daily physical activity. "We found that higher levels of daily moderate-to-vigorous physical activity were associated with better performance on the cognitive tasks measuring attention, memory and multitasking," Ehlers said. "What was notable was that physical activity's effect on cognitive performance was mediated by fatigue. This provides evidence that physical activity interventions targeting fatigue in cancer patients and survivors might provide promising models for improving cognitive function as well." Next, the researchers plan to conduct further studies to establish causation and further explore the pathways of how physical exercise improves cognitive performance. They are working with Digital Artefacts to conduct an iPhone-based study and focusing on diverse populations of breast cancer survivors. "The message for cancer patients and survivors is, get active!" Ehlers said. "Even if it's 10-minute bouts of brisk walking. It's not a magical cure-all, but we've seen many benefits of physical activity for cancer patients and survivors."   Cannabidiol promotes oral ulcer healing by inactivating CMPK2-mediated NLRP3 inflammasome Sichuan University (China), July 26, 2021 Xingying Qi, West China Hospital of Stomatology, Sichuan University, Chengdu, China, presented the oral session "Cannabidiol Promotes Oral Ulcer Healing by Inactivating CMPK2-Mediated NLRP3 Inflammasome" at the virtual 99th General Session & Exhibition of the International Association for Dental Research (IADR), held in conjunction with the 50th Annual Meeting of the American Association for Dental Research (AADR) and the 45th Annual Meeting of the Canadian Association for Dental Research (CADR), on July 21-24, 2021. The oral ulcer is a common oral inflammatory lesion with severe pain but little effective treatment is currently available. Cannabidiol (CBD) is recently emerging as a therapeutic agent for inflammatory diseases. However, the underlying mechanisms are not fully elucidated. Qi and colleagues sought to investigate whether and how CBD could play a therapeutic role in the oral ulcer. Oral ulcer models were performed in the tongue of C57BL/6 mice by acid etching or mechanical trauma, followed by CBD local administration. Samples were harvested for macroscopic and histological evaluation. CBD oral spray on acid- or trauma-induced oral ulcers on mice tongues inhibited inflammation, relieved pain and accelerated lesions closure in a dose-dependent manner. The results show that CBD accelerates oral ulcer healing by inhibiting CMPK2-mediated NLRP3 inflammasome activation and pyroptosis, which is mediated mostly by PPARγ in nucleus and partially by CB1 in plasma membrane. This data may shed light on the development of new therapeutic strategies for oral ulcers.   Algal solution: Could Spirulina modify the microbiome to protect against age-related damage? Louvain Drug Research Institute (Belgium), July 25 2021 Spirulina might help protect against age-related liver inflammation by modifying pathways in the microbiome, say researchers. Consumption of spirulina could help protect against hepatic inflammation in the elderly, according to the new animal research published in Nutrients. Belgian researchers carried out tests on mice, which suggest that the algae Spirulina has an impact on the gut microbiota, which in turn activates the immune system in the gut and improves inflammation in the liver that is associated with ageing. Led by senior author Professor Nathalie Delzenne from the Louvain Drug Research Institute in Belgium, the team said oral feeding of Spirulina was found to modulates several immunological functions involving, among others, the TLR4 pathway in old mice. “The fact that its oral consumption can influence both gut immunity and systemic sites, such as the liver, suggests that its immune action is not confined to the gut immune system,” wrote the team – who said the findings open the way to new therapeutic tools “in the management of immune alterations in aging, based on gut microbe-host interactions.” Furthermore, they suggested that improvement of the homeostasis in the gut ecosystem ‘could be essential' during the aging process, “and, in this perspective, dietary manipulation of the gut microbiota of the elderly with Spirulina, may represent a tool for preserving a healthy gastrointestinal microbial community in addition to its beneficial effects on immune function.” Study details Delzenne and colleagues noted that while the possible cardiovascular and immune support benefits of Spirulina have been fairly widely reported, the new study brings a fresh approach by testing whether the effects could be related to a modulation of gut micrbiota. In the trial, young mice aged three months were fed a standard diet, while older mice aged 24 months were fed a standard diet either with or without 5% Spirulina for six weeks. Upton supplementation with Spirulina, the team reported several changes to gut microbiota composition, including an increase in Roseburia and Lactobacillus populations. “Interestingly, parameters related to the innate immunity are upregulated in the small intestine of Spirulina-treated mice,” said the team. “Furthermore, the supplementation with Spirulina reduces several hepatic inflammatory and oxidative stress markers that are upregulated in old mice versus young mice.” Expression of several genetic and biochemical markers of inflammation and immunity were altered by supplementation with Spirulina, said the team. In particular, the transcription factor Foxp3 – involved in the differentiation of T cells into regulatory T cells (Tregs) – and MCP1 were increased due to Spirulina supplementation in old mice. Old mice that consumed Spirulina also showed activation of several immune parameters including Foxp3 in the ileum – suggesting an improvement of the gut immune function upon Spirulina treatment in this segment, said the Belgian researchers. Furthermore, Spirulina supplementation upregulated both TLR2 and TLR4 expression in the ileum of aged mice. “In accordance with these results, a solution of Spirulina (5%) exhibited a TLR4 agonist activity similar to the one reached in old-SP mice, suggesting a direct effect of the Spirulina, itself, on the TLR4 pathway,” they added. Microbiome mechanisms While the positive effect of Spirulina on the microbiome and liver inflammation is clear, the team noted that the mechanism by which the algae could change the composition of the intestinal microbiota remains unanswered. One possible mechanism could be the presence of antimicrobial substances produced by Spirulina, they said. “On the other hand, antimicrobial peptides (AMPs) could be mediators of the nutritional modulation of the gut microbiota.” “In the present study, RegIIIγ and Pla2g2 were increased by the supplementation with Spirulina, suggesting that the host contributes to the reduction and modification of the microbial community by modulating the production of specific AMPs,” they added.

You probably know that the kidneys play an important role in maintaining blood pressure within the normal range. You might also know that they do this by regulating blood volume and the degree of arterial contraction or dilation (the systemic vascular resistance). But do you know how the kidneys do this? The answer is the kidneys accomplish this primarily through a set of hormones and enzymes known together as the renin-angiotensin-aldosterone system (RAAS). In this brick, we will discuss the components, functions, and regulation of the RAAS. Renin is an enzyme released by the kidneys that ultimately causes the formation of the hormone angiotensin II (Ang II) in the body—which in turn stimulates the release of the hormone aldosterone from the adrenal cortex. Ang II and aldosterone act in a number of ways to increase blood volume and blood pressure. RAAS acts to increase sodium reabsorption in the kidney, increase vascular tone, and even stimulate antidiuretic hormone (ADH) to reabsorb more water: all of these defend our extracellular volume and blood pressure. RAAS is therefore a critical system for keeping us upright! After listening to this Audio Brick, you should be able to: Outline the renin-angiotensin-aldosterone system, including sensors, factors that control it, sources of hormone release, and the actions of each hormone. Describe the mechanisms by which the renin-angiotensin-aldosterone system regulates blood pressure. Compare and contrast tubuloglomerular feedback with the renin-angiotensin-aldosterone system. You can also check out the original brick from our Endocrine collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks.  After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology. *** If you enjoyed this episode, we'd love for you to leave a review on Apple Podcasts.  It helps with our visibility, and the more med students (or future med students) listen to the podcast, the more we can provide to the future physicians of the world. Follow USMLE-Rx at: Facebook: www.facebook.com/usmlerx Blog: www.firstaidteam.com Twitter: https://twitter.com/firstaidteam Instagram: https://www.instagram.com/firstaidteam/ YouTube: www.youtube.com/USMLERX Learn how you can access over 150 of our bricks for FREE: https://usmlerx.wpengine.com/free-bricks/ from our Musculoskeletal, Skin, and Connective Tissue collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks.  After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology.

  Vidcast:  https://youtu.be/ezZII2jLS2c   zaaThose taking anti-hypertensive drugs that cross the blood-brain barrier showed better memory function compared with those on blood pressure medications that cannot cross that barrier.  Neuroscientists at UC-Irvine now publish their meta-analysis of 14 global studies covering nearly 13,000 adults.   Those taking drugs in the ACE inhibitor or the ARB categories showed better memory recall during a 3 year followup period than those taking other blood pressure control medications.  ACE inhibitors included captopril, fosinopril, lisinopril, perindopril, ramipril, and trandolapril.  ARB drugs were telmisartan and candesartan.   These observations suggest that drugs capable of modulating angiotensin and crossing the blood-brain barrier may slow cognitive deterioration and dementia.   https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.121.17049   #dementia #antihypertensives #angiotensin #aceinhibitor #arb #bloodbrainbarrier  

Ob nach einer Hyaluron Behandlung die Corona Impfung dazu führen kann, dass Schwellungen auftreten oder ob nach einer Corona Impfung eine Hyaluron Behandlung stattfinden kann, erklärt Dr. med. Robert Kasten auf Basis aktuellster Daten in diesem Video.

Dr. Ray Peat, Ph.D Renowned Nutritional Counselor Ray Peat acquired his PhD from the University of Oregon with a specialization in physiology. He started his work on hormones in 1968 and wrote his dissertation in 1972 in which he outlined his ideas on progesterone and the hormones closely related to it. His main thesis is that energy and structure are interdependent at every level. Please consider signing up to Dr. Peat’s terrific newsletter. Comes out every other month at an incredibly low cost..email Dr. Peat here Show highlights: There’s no scientific evidence that masks or lockdowns help, according to Dr. Ray Peat. The mRNA vaccines could have long-range degenerative effects. Mike Yeadon, an ex-vice president of Pfizer, criticized the mRNA vaccines on a YouTube video, and Google quickly attacked it as fake news. What does angiotensin have to do with Covid? Why do the vaccines that cause our body to produce so-called “harmless” spike proteins turn us into our own toxic system? Vaccine experiments by the CDC on Guatemalan orphans showed that the innate immune system is disrupted and becomes overactive, creating allergies. Why did the CDC promote Paul Erhlich’s flawed research and create our current “doctrine of immunity”? pure-organic-sulfur How can vaccinations become deadly? Have vaccinations created an epidemic of allergies? “There really isn’t any part of our body that isn’t involved in immunity,” says Dr. Peat. What is Polly Matzinger’s “danger model theory” of how the immune system actually works? How does Jamie Cunliffe’s “damage theory” relate to vaccines? Why do African climate and poverty increase the chances of parasites and AIDS? How do vitamin D and vitamin A help heal infections? Dr. Peat discusses molecular biologist Peter Duesberg’s pioneering work in virology and AIDS. Injecting anything into the muscles — even vitamins — affects immunity. Angiotensin creates an estrogen cascade that weakens the restorative and energetic systems. Accumulative effects of adapting to defective systems cause accelerated aging. Living at low altitudes speeds up aging. Why is it easier for babies to recover from injuries without forming scar tissue? A baby has a metabolic rate three times higher than an older person. Carbon dioxide increases tissue restoration without scar tissue. What happens with every thousand feet of altitude? Does living at a high altitude prevent cancer and heart disease? Anything that raises your body temperature is a good exercise. Dr. Peat talks about the best forms of exercise. Why is it a good idea to stick to concentric contractions during exercise? Why are eccentric contractions harmful? What’s the difference between running for short distances versus running for long distances? What happens when you run at high altitudes? Looking at the body as a machine leads to incorrect judgements about health and disease. A listener asks about protecting the liver from alcohol toxicity without resorting to milk thistle. Is fructose an antidote to alcohol poisoning? What part does reductive stress play in inflammation? Why is an excess of electrons a problem? Do reducing agents such as cysteine and glutathione cause random tissue destruction? Are we being lied to about methyl donors? How does electron excess affect iron and copper? Vitamin C supplements can produce free radicals at the level of damage from radiation therapy. What are the origins of the biological stigma against milk? How did it create our current baby food culture, turning the feeding of babies over to industry instead of the mother. Why are grass-fed beef and butter better than their grain-fed counterparts? Is grass high in flavonoids? Orange juice is high in flavonoids and potassium. A listener asks about increasing testosterone. Orange juice, carbohydrates, and cocoa butter are discussed. Saturated fat can prevent heart cell death. Polyunsaturated fat causes heart cells to die.

Commentary by Dr. Valentin Fuster

The exciting conclusion to Chapter Two: Renal Circulation and Glomerular Filtration Rate - Determinants of GFR - First step in making urine is separation of an ultrafiltrate - Governed by starling forces - Balance of hydraulic and osmotic forces - GFR = LpS (P gc – P us - Osmotic Pressure Cap p) - Normal GFR 95 in women, 120 in men - Cap Hydrolic pressure remains constant - glom cap Oncotic progressively rises - Due to filtration of protein free fluid (protein concentration rises in the capillary) - Filtration gradient begins at 13 mmHg and falls to zero after filtration of 20% or RPF! - GFR is capped at 20% of RPF called filtration equilibrium - So GFR is dependent on RPF, unless you can change glomerular hydraulic pressure - Glomerular hydraulic pressure is controlled by balance of twin arteriole (afferent and efferent) - Constriction of afferent arteriole reduces RPF, GFR, and glom pressure - Dilation of afferent arteriole increases RPF, GFR, and glom pressure - Constriction of the efferent arteriole increases Glom pressure, increasing GFR - Besides glom hydrostatic pressure the other starlings forces are rarely relevant to changes in GFRLetty says: referred to this NEJM review article later JC thought she was referring to something else -see #2- and then Roger referred to this again)Normotensive Acute Renal Failure from Gary Abuelo in NEJM 2007. https://www.nejm.org/doi/10.1056/NEJMra064398 (note in this article, Dr. Abuelo acknowledges the newer terminology of the time, AKI rather than ARF but chooses not to embrace it). In figure 2, he highlights the classic examples of how autoregulation can be affected. In the table, additional examples are provided but all within the framework of alterations related to autoregulation and the interplay between the two resistance vessels.- Regulation of GFR - Autoregulation - The ability to keep glomerular pressure constant over wide range of systemic arterial pressure - When pressure < 70 autoregulation fails and GFR will fall with decreases in systemic pressure - When pressure falls below 40-50 GFR ceases - At least some of this autoregulation is mediated with Ang2. Giving ACEi markedly disrupts autoregulation - Nitric oxide, not important - TGF - Chloride in macula densa - Blocked by furosemide - Group affect of nephrons - Ang 2 sensitizes - Adenosine mediates - Function of TGF - 90% of filtrate is reabsobed in PT and LOH - 10% is reabsobed dismally - Need to control the amount of fluid delivered distally to prevent overwhelming the resorptive capacity of the distal nephron - Talks about acute renal success without naming it (but did reference it) - Mentions glucosuria blunts TGF. Hmmm... - Neurohormonal influences - Volume changes in ang2, sympathetic NS - Role of PGE - Interesting discussion of change of the nephrons perfumed with volume depletion, shifting of blood from outer coretex to inner medullary cortical gloms with their long loops - Dopamine and ANP both increased with volume up - Dopamine causes vasodilation of afferent and efferent arteriole - ANP causes afferent vasodilation and efferent vasodilation constriction, increasing GFR without affecting RPF - Glomerular hemodynamics and renal failure - Decreased glomerular mass results in hyperfiltration of remaining gloms - Mediated through afferent vasodilationJC talks about this classic study in critical care: High vs. Low blood pressure target in Septic Shock. https://www.nejm.org/doi/pdf/10.1056/NEJMoa1312173In this multi-center open label trial of 776 patients randomized to either a MAP of 65-70 or 80-85 with the primary endpoint of mortality. There was no difference in mortality at 28 days between the two groups (but a small difference in AKI in the patients who had chronic HTN- in the higher BP target, there was a decrease in need for RRT; there was also a higher incidence of afib in the high target group overall). - Results in compensation and stable GFR in short term, long term maladaptive - Reason for ACEi- Clinical Evaluation of Renal Circulation - Concept of clearance and measurement of GFR - GFR as an index of functioning renal mass - Had a patient today s/p nephrotomy, 72 years old, Cr0.9!Melanie referred to this article in Circulation which demonstrates that SGLT2 inhibitors do decrease single nephron GFR (in mice) and that this is related to a decrease in the afferent arteriole diameter and then they show that this is related to a local increase in adenosine. Kidokoro K, Cherney DZI et al. Evaluation of glomerular hemodynamic function by empagliflozin in diabetic mice using in vivo imaging Circulation 140 (4) 2019https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.037418 - Fall in GFR earlier and only sign of renal disease - Serial monitoring is used to assess severity and follow the course of disease - GFR is useful for dosing drugs - How to measure GFR - Consider fructose polysaccharide inulin (love the parenthetical, not insulin) - Inulin filtered = inulin excreted - Filtered inulin = plasma inulin concentration x GFR - Inulin excreted = urine concentration x urine volume - Use Alber a to get GFR = [Urine]insulin x urine volume / [plasma]inulin - GFR = inulin clearance - There is not an available assay for inulin - Creatinine clearance - Freely filtered - Not reanbsorbed - Not metabolized - Small amount excreted - CrCl exceeds GFR by 10-20%Roger says the SGLT2 inhibitor story is about the afferent arteriole and he thought it reminded him of the MDRD study and the concept that the lower protein intake would be protective and delay the progression of CKD. The concept was that low protein diets would decrease glomerular pressure by decreasing the intake of amino acids that lead to arteriolar vasodilation and increased GFR. Klaur S, Levey AS et al. The effects of Dietary Protein Restirciton and blood-pressure control on the progression of chronic renal disease. NEJM 1994 330:877-884. https://www.nejm.org/doi/full/10.1056/nejm199403313301301 - Compensated for by noncreatinine chromogens (acetone proteins, as Orbi acid, pyruvate) that over estimate Cr by 10-20% - Cr Cl = [Urine]cr x urine volume / [Plasma]cr - Two major limitations - Incomplete collections - 20-25 mg/kg in adult men - 15-20 mg/kg in adult womenThe term “Acute renal success” comes from Thurau K and Boylan JW. Acute renal success. The unexpected logic of oliguria in acute renal failure. Am J Med 1976 61(3): 3038-15. - Falls by 50% from age 50 to 90 to 10 mg/kg - Increased tubular secretion with decreased kidney function - GFR of 40-80 cr secretion may account for as much as 35% of creatinine excretion - In some cases CrCl can exceed GFR by a factor of 2 - Give cimetidine 1200 mg! - It is important to appreciate however that exact knowledge of GFR is not required. More important to know if GFR is changing - Why is radio labeling the solution DTPA and iothalamate? - Talks about the reality of progressive disease despite stable GFR and CrCl - On to plasma Cr and GFRIf you think placing dialysis lines is too easy, here is a wonderful review of micropuncture technique in the kidneys by Volker Vallon.Micropuncturing the Nephron. Pflugers Arch 2009 458(1): 189-201. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954491/ - Creatinine excretion = creatinine production (and this is constant) - Creatinine excretion = [Cr] x GFR = constant - If GFR falls in half, creatinine excretion will fall in half, while creatinine production remains the same, so creatinine will rise and rise until [Cr] x GFR = creatinine production and then it will level off. - Changes in creatinine load - High protein diet can increase it - Vegetarian diet can decrease itJC brought up studies on fenoldopam, of which there are many. This is one such study in patients undergoing cardiac surgery. JAMA 2014 Bove T et al. Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial https://pubmed.ncbi.nlm.nih.gov/25265449/ - Cooked meat can increase Cr by 1 mg/dL - Talks about need for steady state to assess GFR - Talks about the curvilinear relationship - Then he talks Cockcroft GaultThe one, the only: The Cockcroft Gault: Prediction of creatinine clearance from serum creatinine. Nephron 16: 31–41, 1976 https://pubmed.ncbi.nlm.nih.gov/1244564/ - Cirrhosis masks kidney insufficiency, low meat intake, low BUN production - Can someone explain what we are supposed to take from figure 2-12 - Stable Cr does not mean stable kidney diseaseRoger describes the study design for the seminal paper on the use of ACE inhibitors to slow the decline in renal function in diabetic kidney disease (then called diabetic nephropathy) and the decision to use the doubling of the serum creatinine as an endpoint. Lewis EJ The effect of Angiotensin-converting-enzyme inhibition on diabetic nephropathy NEJM 1993 https://www.nejm.org/doi/full/10.1056/NEJM199311113292004 - Ketoacidosis can raise the Cr 0.5 to 2.0mg/dL - On to BUN - Destination of amino acids produces ammonia - We detoxify ammonia by converting to urea - Increased with increased protein load - Increased catabolismMelanie mentioned an old study on ingestion of expired blood: Cohen TD. Induced azotemia in humans following massive protein and blood ingestion and the mechanism of azotemia in gastrointestinal hemorrhage. AM J Med Sci 1956 https://pubmed.ncbi.nlm.nih.gov/13302213/ - Tetracycline causes decreased anabolism - Trauma - Steroids - Urea excretion is variable and tied to hydration and FF - Renal plasma flow and PAH

To start comparing quotes and simplify insurance-buying check out Policygenius: http://policygenius.com/minuteearth. Thanks to Policygenius for sponsoring this video! I found a really cool coronavirus illustration that led me to learn about viral attachment and entry. LEARN MORE ************** To learn more about this topic, start your googling with these keywords: Virus: a submicroscopic infectious agent that replicates only inside the living cells of an organism. The study of viruses is known as virology. Virion: a complete virus particle, and consists of nucleic acid surrounded by a protective coat of protein called a capsid. Coronaviruses: a group of related RNA viruses that cause diseases in mammals and birds. In humans and birds, they cause respiratory tract infections that can range from mild to lethal and include some cases of the common cold, SARS, MERS, and COVID-19. SARS-CoV-2: the virus that causes coronavirus disease 2019 (COVID-19), the respiratory illness responsible for the COVID-19 pandemic. Class I fusion proteins: resemble influenza virus hemagglutinin in their structure. Post-fusion, the active site has a trimer of α-helical coiled-coils Proteins featured in this video: - SARS-CoV-2 Spike (S) Protein - Heparan Sulfate Proteoglycan (HSPG) (Syndecan-4, especifically) - Angiotensin-converting enzyme 2 (ACE2) - Furin - Transmembrane protease, serine 2 (TMPRSS2) If you liked this week’s video, you might also like: Coronaviruses 101: Focus on Molecular Virology by Britt Glaunsinger https://www.youtube.com/watch?v=8_bOhZd6ieM Virology Lectures 2021: Attachment and entry by Vincent Racaniello https://www.youtube.com/watch?v=7grtc4k1fhg Building a visual consensus model of the SARS-CoV-2 life cycle https://animationlab.utah.edu/cova SUPPORT MINUTEEARTH ************************** If you like what we do, you can help us!: - Become our patron: https://patreon.com/MinuteEarth - Share this video with your friends and family - Leave us a comment (we read them!) CREDITS ********* Ever Salazar | Script Writer, Narrator, Director, and Illustrator Aldo de Vos (Know Art) | Music MinuteEarth is produced by Neptune Studios LLC https://neptunestudios.info OUR STAFF ************ Sarah Berman • Arcadi Garcia Rius David Goldenberg • Julián Gustavo Gómez Melissa Hayes • Alex Reich • Henry Reich Peter Reich • Ever Salazar • Kate Yoshida OTHER CREDITS ***************** SARS-CoV-2 Fusion, 2020 - Illustration by David S. Goodsell, RCSB Protein Data Bank; doi: 10.2210/rcsb_pdb/goodsell-gallery-026 http://pdb101.rcsb.org/sci-art/goodsell-gallery/sars-cov-2-fusion Coronavirus outbreak (covid 19) explained through 3D Medical Animation - Video by scientificanimations.com https://youtu.be/I-Yd-_XIWJg?t=208 Coronavirus, Explained: This Pandemic - Video by Netflix https://www.netflix.com/title/81273378 How the Coronavirus Hijacks Your Cells - Video by Bloomberg Quicktake https://youtu.be/4S3DXXtRZZg?t=128 Ink Drop/Drip in water - Video by CyberWebFX https://www.youtube.com/c/CyberWebFX OUR LINKS ************ Youtube | https://youtube.com/MinuteEarth TikTok | https://tiktok.com/@minuteearth Twitter | https://twitter.com/MinuteEarth Instagram | https://instagram.com/minute_earth Facebook | https://facebook.com/Minuteearth Website | https://minuteearth.com Apple Podcasts| https://podcasts.apple.com/us/podcast/minuteearth/id649211176 REFERENCES ************** Afzelius, B. (1994). Ultrastructure of human nasal epithelium during an episode of coronavirus infection. Virchows Archiv 424:295-300 Bestle, D., Heindl, M., Limburg, H., et all (2020). TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells. doi: 10.26508/lsa.202000786 Buijsers B., et al (2020) Increased Plasma Heparanase Activity in COVID-19 Patients. Front. Immunol. 11:575047. doi: 10.3389/fimmu.2020.575047 Casalino, L., et al (2020). Beyond Shielding: The Roles of Glycans in the SARS-CoV-2 Spike Protein ACS Central Science 2020 6 (10), 1722-1734. doi: 10.1021/acscentsci.0c01056 Clausen, T. M., et al (2020). SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2. Cell Volume 183, Issue 4, Pages 1043-1057.e15. doi: 10.1016/j.cell.2020.09.033 Elenius, K & Jalkanen, M. (1994). Function of the syndecans - a family of cell surface proteoglycans. Journal of Cell Science 107, 2975-2982 Shang, J. et al (2020). Cell entry mechanisms of SARS-CoV-2. PNAS May 26, 2020 117 (21) 11727-11734. doi: 10.1073/pnas.2003138117 Thomas, G. (2002). Furin at the cutting edge: From protein traffic to embryogenesis and disease. Nat Rev Mol Cell Biol. 2002 October; 3(10): 753–766 Zhang, Q., et al (2020). Heparan sulfate assists SARS-CoV-2 in cell entry and can be targeted by approved drugs in vitro. Cell Discovery (2020) 6:80. doi: 10.1038/s41421-020-00222-5

  Vidcast:  https://youtu.be/9ws7humxWQQ   Early in the CoVid pandemic, concerns arose about using ACE inhibitors and angiogensin receptor blockers (ARBs) since the ACE2 receptor is the entry point for the CoVid virus into human cells.  A just published study from the University of Pennsylvania suggests that these drugs are safe and perhaps even helpful.   Penn investigators studied 152 CoVid patients being treated with various blood pressure meds.   Their data showed that discontinuing those drugs had no positive effects on need for ventilation, incidence of organ failure, or death rate.   If you are on anti-hypertensive drugs in the ACE inhibitor and angiotensin receptor blocking classes, don’t stop taking them if you develop CoVid.    https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30558-0/fulltext   #covid #aceinhibitor #arb  

Commentary by Dr. Virginia Hahn

In today's podcast, I review the pathophysiology of the Renin Angiotensin Aldosterone System (RAAS). Let's Review!

Riaz Aziz talks to Professor Gareth Auckland from Queen Marys university about his November 2020 article ‘Angiotensin converting enzyme inhibitors and angiotensin receptor blockers’ We talk about their use in the perioperative setting, the current evidence and cardiac dysfunction post operatively.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.12.336016v1?rss=1 Authors: Ni, D., Lau, K., Lehmann, F., Fraenkli, A., Hacker, D., Pojer, F., Stahlberg, H. Abstract: The human membrane protein Angiotensin-converting enzyme 2 (hACE2) acts as the main receptor for host cells invasion of the new coronavirus SARS-CoV-2. The viral surface glycoprotein Spike binds to hACE2, which triggers virus entry into cells. As of today, the role of hACE2 for virus fusion is not well understood. Blocking the transition of Spike from its prefusion to post-fusion state might be a strategy to prevent or treat COVID-19. Here we report a single particle cryo-electron microscopy analysis of SARS-CoV-2 trimeric Spike in presence of the human ACE2 ectodomain. The binding of purified hACE2 ectodomain to Spike induces the disassembly of the trimeric form of Spike and a structural rearrangement of its S1 domain to form a stable, monomeric complex with hACE2. This observed hACE2 dependent dissociation of the Spike trimer suggests a mechanism for the therapeutic role of recombinant soluble hACE2 for treatment of COVID-19. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.08.331157v1?rss=1 Authors: Suzuki, Y. J., Ding, Q., Shults, N. V., Harris, B. T. Abstract: Alzheimers disease is a chronic neurodegenerative disorder and represents the main cause of dementia. Currently, the world is suffering from the pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses angiotensin-converting enzyme 2 (ACE2) as a receptor to enter the host cells. In COVID-19, neurological manifestations have been reported to occur. The present study demonstrates that the protein expression level of ACE2 is upregulated in the brain of Alzheimers disease patients. The increased ACE2 expression is not age-dependent, suggesting the direct relationship between Alzheimers disease and the ACE2 expression. Oxidative stress has been implicated in the pathogenesis of Alzheimers disease, and Alzheimers disease brains examined in this study also exhibited higher carbonylated proteins as well as increased thiol oxidation state of peroxiredoxin 6 (Prx6). The positive correlation was found between the increased ACE2 protein expression and oxidative stress in Alzheimers disease brain. Thus, the present study reveals the relationships between Alzheimers disease and ACE2, the receptor for SARS-CoV-2. These results warrant monitoring Alzheimers disease patients with COVID-19 carefully for the possible higher viral load in the brain and long-term adverse neurological consequences. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.06.284901v1?rss=1 Authors: Bhattacharjee, S., Bhattacharyya, R., Sengupta, J. Abstract: The pathogenesis of novel SARS-CoV-2 virus initiates through recognition of ACE2 receptor (Angiotensin-converting enzyme 2) of the host cells by the receptor-binding domain (RBD) located at spikes of the virus. Following receptor-recognition, proteolytic cleavage between S1 and S2 subunits of the spike protein occurs with subsequent release of fusion peptide. Here, we report our study on allosteric communication within RBD that propagates the signal from ACE2-binding site towards allosteric site for the post-binding activation of proteolytic cleavage. Using MD simulations, we have demonstrated allosteric crosstalk within RBD in apo- and receptor-bound states where dynamic correlated motions and electrostatic energy perturbations contribute. While allostery, based on correlated motions, dominates inherent distal communication in apo-RBD, electrostatic energy perturbations determine favorable crosstalk within RBD upon binding to ACE2. Notably, allosteric path is constituted with evolutionarily conserved residues pointing towards their biological relevance. As revealed from recent structures, in the trimeric arrangement of spike, RBD of one copy interacts with S2 domain of another copy. Interestingly, the allosteric site identified is in direct contact (H-bonded) with a region in RBD that corresponds to the interacting region of RBD of one copy with S2 of another copy in trimeric constitution. Apparently, inter-monomer allosteric communication orchestrates concerted action of the trimer. Based on our results, we propose the allosteric loop of RBD as a potential drug target. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.06.285023v1?rss=1 Authors: Garg, A., Kumar, G., Sinha, S. Abstract: nCOVID-19 virus makes cellular entry using its spike protein protruding out on its surface. Angiotensin converting enzyme 2 receptor has been identified as a receptor that mediates the viral entry by binding with the receptor binding motif of spike protein. In the present study, we elucidate the significance of N-terminal domain of spike protein in spike-receptor interactions. Recent clinical reports indicate a link between nCOVID-19 infections with patient comorbidities. The underlying reason behind this relationship is not clear. Using molecular docking, we study the affinity of the nCOVID-19 spike protein with cell receptors overexpressed under disease conditions. Our results suggest that certain cell receptors such as DC/L-SIGN, DPP4, IL22R and ephrin receptors could act as potential receptors for the spike protein. The receptor binding domain of nCOVID-19 is more flexible than that of SARS-COV and has a high propensity to undergo phase separation. Higher flexibility of nCOVID-19 receptor binding domain might enable it to bind multiple receptor partners. Further experimental work on the association of these receptors with spike protein may help us to explain the severity of nCOVID-19 infection in patients with comorbidities. Copy rights belong to original authors. Visit the link for more info

Commentary by Dr. Valentin Fuster

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.17.254359v1?rss=1 Authors: Khan, H., Hussain, T., Kataria, M., SETH, A., Malik, M. Z., Dash, A., Chand, S., KHAN, M. A. Abstract: Hypertension is one of a major reason of mortality and morbidity and it is associated with heart and renal disease. The aim of this study is to find out the antihypertensive role of bioactive compounds from selected medicinal plants targeting ACE molecule which so far is not known. The plants taken in this study were Moringa oleifera, Azadirachta indica, and Hibiscus sabdariffa. The nitric oxide and superoxide scavenging property vary from 39.50% to 68% and 37.67 % to 75.50 %. respectively. The inhibition of ACE activity was found maximally in methanolic extract of A. indica (74 %), followed by H. sabdariffa (73.4%), and least in M. oleifera (71.8 %). The bioactive chloroform fraction was characterized for the presence of compound using standard techniques such as LCMS and NMR (13C-NMR 1H-NMR). The results revealed the presence of beta-sitosterol in M. oleifera, azadiradionolide in A. indica and hibiscitrin in H. sabdariffa. The compounds have shown significant low binding energy for hibiscitrin (-12.3kcal/mol), beta-sitosterol (-11.2kcal/mol) and azadiradionolide (-11.3kcal/mol) indicating the high efficacy of binding on the enzyme. While, binding energy of drug captopril was -5.6kcal/mol & enalpril -8.1kcal/mol in the same pocket of the ACE molecule. Upon subjecting molecular dynamic simulation results indicated that beta sitosterol complex provided more compactness than the hibiscitrin and azadiradionolide compounds. The current study delivers a new perspective for the drug development against systolic blood pressure regulation and also opens new horizons for considering alternate highly potent drug target for hypertension. Copy rights belong to original authors. Visit the link for more info

This week, I provide a comprehensive introduction to ARBs. Citations are available in the video format on YouTube.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.24.219857v1?rss=1 Authors: Esparza, T. J., Brody, D. L. Abstract: There are currently no approved effective treatments for SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Nanobodies are 12-15 kDa single-domain antibody fragments that are more stable and amenable to large-scale production compared to conventional antibodies. Nanobodies can also be administered in an inhaled form directly to the lungs. We have isolated several nanobodies that bind to the SARS-CoV-2 spike protein receptor binding domain and block spike protein interaction with the angiotensin converting enzyme 2 (ACE2) receptor. The SARS-CoV-2 spike protein is responsible for viral entry into human cells via interaction with ACE2 on the cell surface. The lead therapeutic candidate, NIH-CoVnb-112, binds to the SARS-CoV-2 spike protein receptor binding domain at approximately 5 nM affinity, and blocks spike protein interaction with the human ACE2 receptor at approximately 0.02 micrograms/mL EC50 (1.1 nM). The affinity and blocking potency of NIH-CoVnb-112 are substantially better than previously reported candidate nanobody therapeutics for SARS CoV-2, and bind to a distinct site. Furthermore, NIH-CoVnb-112 blocks interaction between ACE2 and several high affinity variant forms of the spike protein. When multimerized or combined with other nanobodies, the effective affinity and blocking interactions may be even more potent, as has been well described for other nanobody therapeutics. These resulting nanobodies have therapeutic, preventative, and diagnostic potential. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.24.162941v1?rss=1 Authors: Singh, V., Beer, A., Kraus, A., Zhang, X., Xue, J., Hermann, D. M., Gunzer, M. Abstract: Background: The newly emerged severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused a worldwide pandemic of human respiratory disease. Angiotensin-converting enzyme (ACE) 2 is the key receptor on lung epithelial cells to facilitate initial binding and infection of SARS-CoV-2. The binding to ACE2 is mediated via the spike glycoprotein present on the virus surface. Recent clinical data have demonstrated that patients suffering from stroke are particularly susceptible to severe courses of SARS-CoV-2 infection, thus forming a defined risk group. However, a mechanistic explanation for this finding is lacking. Sterile tissue injuries including stroke induce lymphocytopenia and systemic inflammation that might modulate the expression levels of surface proteins in distant organs. Whether systemic inflammation following stroke can specifically modulate ACE2 expression in the lung has not been investigated. Methods: Mice were subjected to transient middle cerebral artery occlusion (MCAO) for 45 min and sacrificed after 24 h and 72 h for analysis of brain and lung tissues. Gene expression and protein levels of ACE2, ACE, IL-6 and IL1{beta} were measured by quantitative PCR and Western blot, respectively. Immune cell populations in lymphoid organs were analyzed by flow cytometry. Results: Strikingly, 24 h after stroke, we observed a substantial increase in the expression of ACE2 both on the transcriptional and protein levels in the lungs of MCAO mice compared to sham-operated mice. This increased expression persisted until day 3 after stroke. In addition, MCAO increased the expression of inflammatory cytokines IL-6 and IL-1{beta} in the lungs. Higher gene expression of cytokines IL-6 and IL-1{beta} was found in ischemic brain hemispheres and a reduced number of T-lymphocytes were present in the blood and spleen as an indicator of sterile tissue injury-induced immunosuppression. Conclusions: We demonstrate significantly augmented ACE2 levels and inflammation in murine lungs after experimental stroke. These pre-clinical findings might explain the clinical observation that patients with pre-existing stroke represent a high-risk group for the development of severe SARS-CoV-2 infections. Our studies call for further investigations into the underlying signaling mechanisms and possible therapeutic interventions. Copy rights belong to original authors. Visit the link for more info

Commentary by Dr. Valentin Fuster

High fructose consumption is associated with metabolic syndrome, but the mechanisms are not well understood. Listen as Associate Editor Fabio Recchia (Temple University and Scuola Superiore Sant'Anna) interviews lead author An Huang (New York Medical College) and content expert Zsolt Bagi (Medical College of Georgia) about the new study by Froogh et al, which used an animal model to test the hypothesis that a high fructose diet elicits a chymase-dependent increase in angiotensin II production and oxidative stress. In this technical tour de force of a podcast, we unpack the complexities of EET as a protective factor against oxidative stress. Listen as our experts discuss metabolic syndrome in the context of COVID-19, as well as the potential clinical translation of chymase and soluble epoxide hydrolase as therapeutic targets for the treatment of metabolic syndrome.   Ghezal Froogh, Sharath Kandhi, Roopa Duvvi, Yicong Le, Zan Weng, Norah Alruwaili, Jonathan O. Ashe, Dong Sun, An Huang The contribution of chymase-dependent formation of ANG II to cardiac dysfunction in metabolic syndrome of young rats: roles of fructose and EETs Am J Physiol Heart Circ Physiol, published April 2, 2020. DOI: doi.org/10.1152/ ajpheart.00633.2019

Dr. Don Clum and I had an amazing conversation that spanned from simple lifestyle changes you could make to COVID 19, Vitamin D3, insulin resistance, and Angiotensin-converting enzyme 2 receptors.  I know... you are thinking what in the world?   This is a great episode for those that want to IMPROVE health, learn a little science, and know some simple steps to GET BETTER!!!   Here's a little about our guest: Dr. Don Clum graduated from Life University in Marietta, GA in 1997 with a degree in Human Nutrition. He then moved to Life Chiropractic College West in California where he graduated with his Doctorate of Chiropractic in 2000. After graduation, Dr. Clum moved to San Jose, Costa Rica where he was invited to work with the Costa Rican Olympic Committee and Athletes. Dr. Clum participated in the National, Central American and Caribbean and Central American Games as the team chiropractor and as the official chiropractor for two professional soccer teams. As a frequent guest on National Television and Radio, Dr. Clum was influential in bringing the gift of holistic health care to the people of Central America and worked with the government programs, instituting W.H.O. procedures and working directly with the indigenous populations of Costa Rica. He was sought after as a speaker and has presented to various professional sports teams, universities, medical groups, medical and chiropractic schools, businesses and government agencies. Dr. Clum was instrumental in forming the first Colegio or “Board” and enacting the first legislation recognizing chiropractic as a licensed and legal healing profession in Costa Rica. After eight years in Costa Rica, Dr. Clum traveled to Castilla La Mancha, Spain, where he practiced and did consulting for two years. He returned to the U.S.A. in 2010 when he and his wife started a fully integrated wellness center bringing holistic services of chiropractic, massage, metabolic nutrition, metabolic workouts in their onsite gym, wellness psychology, and medical services collaboration. Dr. Clum also collaborated in transitioning a traditional pain management medical practice into a wellness center with holistic services and served as the director of the onsite lab. Dr. Clum's success in creating integrated programs for insulin resistance specifically focusing on diabetes, diabetes prevention, metabolic syndrome, weight loss resistance, obesity, and cardiometabolic issues led him to join a national corporate wellness and population health company, ADURO Inc., in 2014 to date serving 140 employers and over 1,000,000 employees. Here at ADURO Dr. Clum has designed and delivered the first alternative diabetes prevention program that rivals and beats the national statistics of the National Diabetes Prevention Program from the N.I.H., and C.D.C. In 2015 Dr. Clum was accepted into and started a Ph.D. program in Health Psychology at Northcentral University where his emphasis of study is centered on the relationship of chronic stress, food and general addiction cycle, and early onset of male depression in what is termed the Irritable Male Syndrome. Dr. Clum is fully bilingual, speaking Spanish as well as English, and enjoys spending time with his wife and three wonderful children. ______________________ https://yourwellnesstribe.com/ https://www.facebook.com/don.clum Check out products we like> https://www.amazon.com/shop/lifestylelocker www.LifestyleLocker.com www.NewYorkChiropractic.com www.Facebook.com/lifestylelocker www.facebook.com/NewYorkChiropractic www.instagram.com/drjoshhandt www.twitter.com/drjoshhandt www.linkedin.com/drjoshhandt FREE Endurance Program http://bit.ly/45DEC iTunes http://bit.ly/LifestyleLockerRadio FREE E-Book. Inside the Locker: https://www.lifestylelocker.com/inside-the-locker-book/ How to pick the right Chiro: http://bit.ly/RightChiro

Listen to CMHC's Senior Planning Committee Member, Dr. Keith C. Ferdinand, Professor of Medicine at the Tulane University School of Medicine in New Orleans, LA, discuss whether ACEis and ARBs should be withdrawn in patients with COVID-19.

How coronavirus kills “healthy” people, with Cate Shanahan, M.D.    Check out my bestselling book, The Carnivore Code:  www.thecarnivorecodebook.com   You can find Dr Cate Shanahan and her new book at www.DrCate.com and www.FatBurnFix.com Dr. Cate Shanahan is a board certified Family Physician. Her expertise is diet-driven disease, specifically the twin roles of PUFAs and sugar in promoting weight gain, insulin resistance, prediabetes and other common diet-driven conditions. Her passion is educational programs that improve productivity & reduce employer healthcare costs by cultivating healthy habits at the individual and organization-wide levels.   After getting her BS in biology from Rutgers University, she trained in biochemistry and genetics at Cornell University’s graduate school before attending Robert Wood Johnson Medical School. She practiced in Hawaii for ten years where she studied ethnobotany and her healthiest patient’s culinary habits. She applied her learning and experiences in all these scientific fields to write Deep Nutrition: Why Your Genes Need Traditional Food. Together with Dr. Tim DiFrancesco and NBA legend Gary Vitti, she created the PRO Nutrition program for the LA Lakers and  helped forge a partnership between Whole Foods Market and numerous NBA teams. In May of 2018 she begin  Director of Metabolic Health for ABC Fine Wine and Spirits, a progressive, family run company interested in saving money by betterment of health.   Time Stamps: 10:24 How do we move forward with the Coronavirus crisis 14:29 Update on Coronavirus numbers. 15:44 What is a Coronavirus and how does it affect us? 18:54 How can ACE Inhibitors and Angiotensin receptor blockers affect those with Covid19? 25:23 Would Stephen recommend taking these medications? 30:03 Are healthy people at risk for this virus? 34:29 How do we define healthy? 38:39 Data on comorbidities and other studies. 46:37 Acute hyperglycemia and insulin resistance’s effect on the immune system. 51:51 Blood glucose levels? 56:59 Immune dysfunction in patients with Diabetes Melitus 57:54 The immune response in people with Diabetes. 1:01:51 Insulin receptor mediated stimulation and T cells. 1:03:39 Does insulin resistance impede our ability to fight a virus? 1:05:29 studies (continued) 1:07:19 Pop Sugar article on obesity. 1:09:03 The role of cholesterol in the immune system/role of fatty acid in defending against viruses 1:18:03 Statins and the immune system 1:32:13 Where to find Stephen’s work? 1:32:49 What is the most radical thing Stephen has done recently? Study mentioned: https://www.sciencedirect.com/science/article/a BluBlox: www.blubox.com use the code CarnivoreMD for 15% off your order   Ancestral Supplements https://ancestralsupplements.com/ Code SALADINOMD on the shopify site to receive 10% off.   White Oak Pastures: Use the code CARNIVOREMD at www.whiteoakpastures.com for 10% off your first order!   JOOVV: www.joovv.com/paul To subscribe to my newsletter visit: carnivoremd.com   My contact information:   Book: www.thecarnivorecodebook.com   PATREON: https://www.patreon.com/paulsaladinomd   SOCIAL MEDIA  Instagram: @carnivoremd Website: carnivoremd.com Twitter:@carnivoremd  Facebook: Paul Saladino MD email: drpaul@carnivoremd.com

The Carnivore Code has arrived and it’s already a bestseller!! Get it here: www.thecarnivorecodebook.com   Stephen attained both his Doctorate of Chiropractic and Masters in Human Nutrition and Functional Medicine from the University of Western States in Portland, OR. He is a health coach, speaker, and the author of two books on health; The Health Evolution: Why Understanding Evolution is the Key to Vibrant Health and The Heart: Our Most Medically Misunderstood Organ. Dr. Hussey guides clients from around the world back to health by using the latest research and health attaining strategies. In his down time he likes to be outdoors, playing sports, reading, writing, and spending time with his wife and their pets.   Time Stamps: 10:24 How do we move forward with the Coronavirus crisis?14:29 Update on Coronavirus numbers.15:44 What is a Coronavirus and how does it affect us?18:54 How can ACE Inhibitors and Angiotensin receptor blockers affect those with Covid19?25:23 Would Stephen recommend taking these medications?30:03 Are healthy people at risk for this virus?34:29 How do we define healthy?38:39 Data on comorbidities and other studies. 46:37 Acute hyperglycemia and insulin resistance’s effect on the immune system.51:51 Blood glucose levels?56:59 Immune dysfunction in patients with Diabetes Melitus 57:54 The immune response in people with Diabetes.1:01:51 Insulin receptor mediated stimulation and T cells.1:03:39 Does insulin resistance impede our ability to fight a virus?1:05:29 studies (continued) 1:07:19 Pop Sugar article on obesity.1:09:03 The role of cholesterol in the immune system/role of fatty acid in defending against viruses 1:18:03 Statins and the immune system 1:32:13 Where to find Stephen’s work?1:32:49 What is the most radical thing Stephen has done recently? BluBlox: www.blubox.com use the code CarnivoreMD for 15% off your order   Ancestral Supplements https://ancestralsupplements.com/ Code SALADINOMD on the shopify site to receive 10% off.   White Oak Pastures: Use the code CARNIVOREMD at www.whiteoakpastures.com for 10% off your first order!   JOOVV: www.joovv.com/paul To subscribe to my newsletter visit: carnivoremd.com   My contact information:   Book: www.thecarnivorecodebook.com   PATREON: https://www.patreon.com/paulsaladinomd   SOCIAL MEDIA  Instagram: @carnivoremd Website: carnivoremd.com Twitter:@carnivoremd  Facebook: Paul Saladino MD email: drpaul@carnivoremd.com

Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley: I'm Greg Hundley, associate editor from the VCU Pauley Heart Center in Richmond, Virginia. Dr Carolyn Lam: Greg today's speaker paper is all about soy products and whether or not there is a benefit with them with regards to risk of coronary heart disease. Now, this has been extremely controversial and today's speech or paper is really important in its findings. Ha ha, I bet you want to get to it right now but I'm going to say, hold on let's get to some other really interesting papers in this series first. Can I start off? You got your coffee? Dr Greg Hundley: Yes. Let's get going Carolyn. Dr Carolyn Lam: So the first paper I want to highlight really talks about myocardial energetics in obesity, and you're going to love this one Greg it's got some really cool MRI techniques. We know that obesity is strongly associated with exercise intolerance and the development of heart failure particularly HFpEF. Well Dr Rayner from University of Oxford and colleagues looked at this carefully in 80 volunteers, which included 35 controls with an average BMI of 24 and 45 obese individuals with an average BMI of 35, who did not have coexisting cardiovascular disease. Now, these participants underwent body composition analysis and MRI of the abdominal liver and myocardial fat content, left ventricular function and 31 Phosphorus Magnetic Resonance Spectroscopy to assess Phosphocreatine ATP and Creatine Kinase Kinetics at rest and during Dobutamine Stress. Dr Greg Hundley: Oh, wow Carolyn, this is right up my alley. You've got MRI imaging for body composition coupled with MR spectroscopy for metabolism, so what did they find? Dr Carolyn Lam: Thanks for putting that simply for us Greg. They found that in the obese resting heart, the myocardial creatine kinase reaction rate is increase, maintaining ATP delivery despite reduced energy stores during increased workload. While the non obese heart increases ATP delivery through creatine kinase the obese heart does not, and this is associated with reduced systolic augmentation and exercise tolerance. Weight Loss reversed these energetic changes, so these findings really highlight myocardial energy delivery via creatine kinase as a potential therapeutic strategy to improve symptoms in obesity related heart disease, as well as a fascinating modifiable pathway involved in the progression to heart failure. Now with this paper the central illustration is so critical, everybody has to pick up that issue and have a look. Furthermore, you must read the elegant editorial by Barry Borlaug and Craig Malloy. Dr Greg Hundley: Oh, you bet Carolyn. Craig always puts these MR spectroscopy papers in such fantastic perspective, really looking forward to that read and such an elegant study. Now, we haven't had Carolyn's quiz in weeks and we're going to get into one. This paper comes from Professor Nina Wettschureck, from the Max-Planck-Institute for Heart and Lung research, and it pertains to the infamous G-protein coupled receptors. Now, Carolyn here's your quiz and guess what, it's just multiple choice. All you have to do is fill in the blank. Dr Carolyn Lam: On G-protein coupled receptors? Dr Greg Hundley: Yeah, I know it's... we know a lot about these, but we're going to learn. So, G-protein coupled receptors are the largest family of transmembrane receptors in eukaryotes. They transduce signals of numerous physio-chemical stimuli including... and Carolyn you have to complete this sentence. So it's neurotransmitters, hormones, local mediators, metabolic or olfactory cues and got to complete the sentence. Is it air resistance? Time? Or light? Dr Carolyn Lam: Space. Dr Greg Hundley: That's not a choice. Dr Carolyn Lam: All right, all right let me guess light. Dr Greg Hundley: That's awesome. Fantastic, great job Carolyn. So in the vascular system the contract alternative vessels is crucially regulated by these GPCRs, including basic constrictors such as Angiotensin two and Endothelin one. In this study the investigators studied the role of GPRC5B, and the regulation of contractility and differentiation in human and murine smooth muscle cells in vitro, as well as in tamoxifen inducible smooth muscle cells Pacific knockout mice under conditions of arterial hypertension and atherosclerosis, and these experiments were done in vivo. Dr Carolyn Lam: Okay, so what were the results? Dr Greg Hundley: They found that GPRC5B regulates vascular smooth muscle tone and differentiation by negatively regulating prostate cycling receptor signaling. Thus, Carolyn inhibition of the interaction between GPRC5B and the prostacyclin receptor might be beneficial in human arterial hypertension and vascular remodeling. What a great new insight into basic science. Well, let me get on I have a clinical paper, and this is on the infamous topic from the COMPASS-PCI trial, Rivaroxaban plus Aspirin versus Aspirin alone in patients with Prior Percutaneous Coronary Intervention from Dr Kevin Bainey at the Canadian VIGOUR Center in University of Alberta. So Carolyn, the cardiovascular outcomes for people using anticoagulation strategies or COMPASS trial demonstrated dual pathway intervention with Rivaroxaban 2.5 milligrams twice daily plus aspirin, and 100 milligrams once daily versus aspirin 100 milligrams once daily, reduced the primary major adverse cardiovascular event outcome of cardiovascular death, MI or stroke as well as mortality in patients with chronic coronary syndromes or peripheral arterial disease. Now, whether this remains true in patients with a history of PCI is unknown. Dr Carolyn Lam: Oh, Greg I'm so disappointed. Why didn't you give me a quiz here? I know about the COMPASS trial. Okay, so what did the author's find? Dr Greg Hundley: So Carolyn of the 27,000 plus patients in COMPASS 16,500 plus patients had chronic coronary syndrome, were randomized to DPI or aspirin and of these 9,862 had prior PCI. So here are the results, DPI compared with aspirin produce consistent reductions in MACE mortality, but with increased major bleeding with or without prior PCI. So among those with prior PCI one year and beyond, the effects on MACE and mortality were consistent irrespective of time since the last PCI. Dr Carolyn Lam: Mm-hmm (affirmative) Interesting implications on dual platelet inhibition. Well, let me tell you a little bit about what's in the mailbag in the rest of this issue. There's a research letter by Dr Joseph Wu on molecular signatures of beneficial class effects of statins on human induced pluripotent stem cell derived cardiomyocytes. We have global rounds by Dr Annika Rosengren and Dr Lars Wallentin on the cardiovascular medicine in Sweden. We have a White Paper by Dr Abhinav Saxena and colleagues on the value of hemodynamic monitoring in patients with cardiogenic shock undergoing mechanical circulatory support. And we also have paired perspective pieces, one by Dr Salim Virani and colleagues on secondary prevention of atherosclerotic cardiovascular disease comparing recent United States and European guidelines on dyslipidemia, and another by Dr Neil Stone and colleagues on comparing primary prevention recommendations with the focus look at the US versus European guidelines on dyslipidemia. Dr Greg Hundley: Very good, Carolyn. Well, I've got a research letter Professor Do-Young Kwon from the Korea University of Ansan Hospital, Korea University College of Medicine and discusses the association of Parkinson's disease with the risk of cardiovascular disease and all-cause mortality, and a nationwide population-based cohort study. In addition, different series of letters Dr Seung-Jung Park from Asan Medical Center at the University of Ulsan College of Medicine, and Professor Lang Li of The First Affiliated Hospital of Guangxi Medical University exchanged letters regarding the article, Clinically Significant Bleeding With Ticagrelor versus Clopidogrel in Korean patients with Acute Coronary Syndromes Intended for Invasive Management, that previously published randomized clinical trial. Then finally one of those great ECG investigations from Dr Miguel Arias, and they have an ECG quiz entitled The Hidden Reveals the Hidden, but really, it's referring to a Brugada ECG pattern and a patient with Wolff-Parkinson-White. I can't wait to get onto that feature article discussing the potential benefits or harms of soy in men and women as it relates to cardiovascular disease. Dr Carolyn Lam: Yeah, you and I Greg let's go. Oh, boy today's feature paper really literally cuts close to the heart for me talking about soy products, and whether or not there's a relationship with cardiovascular health. This remains controversial but thankfully we've got really great data just published in this week's issue, so proud to have the first author with us Dr Qi Sun from Brigham and Women's Hospital, as well as our associate editor who's also an editorialist for this paper and that's Dr Mercedes Carnethon from Northwestern University Feinberg School of Medicine. So welcome both I cannot wait to just jump right into it. Please, Qi, tell us what you found about soy products. Dr Qi Sun: First off this is a prospective cohort study that included three cohort studies, the Nurses’ Health Study and the Nurses’ Health Study II and Health Professionals Follow-Up Study. So those three big prospective cohort follow up studies. Now over the years we have collected much data of diet which has been repeated, reviewed, and assessed over the years, and we have accumulated many cases of cardinal heart disease the numbers are a solid. Now what we found is that the intake isoflavones which are the big family are flavonoids, the higher intake of isoflavones were associated with a lower risk of developing coronary heart disease in those three cohorts of men and women. And in addition because tofu and soy milk are the primary contributor in our guide of isoflavones, we also examine the tofu and soy milk in relation to the risk of cardinal heart disease What we found is that tofu intake is significantly associated with lower risk of developing heart disease, and soy milk is also associated with lower risk of developing heart disease. It's just the association for soy milk, soy milk is not significant. And I think very interestingly we also found that the menopausal status and the postmenopausal hormone use somewhat also modulated association primarily for coffee intake with heart disease risk, in that we found younger women who were before their menopause and also postmenopausal women who did not use hormone will benefit more from tofu intake. In contrast, for postmenopausal women who are using hormone the association was not significant. I think those are the primary findings of our prospective cohort study. Dr Carolyn Lam: Oh my goodness, hallelujah. That's really marvelous and beautifully summarized, Mercedes please explain why was this such a controversial area before? And what does this paper add? Love your editorial by the way. Mercedes Carnethon: We hear a lot about nutritional epidemiology studies, and we have a lot of debates about what we should believe, whether we should change our behavior based on these observational studies and quite often we have discussions about what's new. And I lean on that final point about why I like this particular paper so much, and that's because I found the topic of isoflavones, tofu intake and soy to be extremely relevant to a large proportion of the world's population, whose primary protein intake may be something made from a soybean, heavy and isoflavones. Within the United States it's also relevant even though a smaller proportion of our population relies primarily on vegetarian diet, there is a very large and interested group wondering whether soy intake is safe. There have been discussions about whether there's harm associated with it, and the possibility that it could have beneficial influence on our leading causes of death of coronary heart disease. So I was most thrilled about the innovation of this particular topic, and its methodological rigor. When we think about what we lean on, we lean on large studies, we lean on multiple events and the size of the study allowed the investigators to explore numerous subtleties. Subtleties such as that reported related to the moderation by menopausal status, and that was the point I was most curious about and why I'm really excited to have an opportunity to talk to you today Chi. Can you tell me a little more about the menopausal status finding? Dr Qi Sun: So first off as I mentioned tofu intake was more strongly associated with lower risk of developing heart disease among younger pre-menopausal women, or postmenopausal women who did not use ham. Before that I want to also mention for isoflavones intake where I also found a similar pattern in that isoflavones are more. Appear to be more strongly associated with lower risk also in those two groups of women, although the past by interaction was non-significant. Now in terms of why I think there are a couple reasons why is that, among postmenopausal female or in our use hormone, the isoflavone can function as estrogen and provide at least partially the estrogenic effects that were calculated in postmenopausal women who do not use hormone, and for premenopausal women we think that's probably because before menopausal, the activity of estrogen receptor may be higher than the estrogen receptor after menopausal. So, in reality, the other variables of isoflavones may provide estrogen effects after menopausal. So those are the hypotheses although I have to mention that those hypotheses, we need more evidence to really shed light on the mechanisms underlying those interactions between menopausal status, postmenopausal hormonal use, where's the intake of isoflavones and tofu. Dr Carolyn Lam: So Chi I love that explanation and giving it some biological possibility, although as you said it's a postulation. But may I ask so what's the implication for men? I lived with a man who thinks if he takes soy he's going to grow boobs. So what... did you see any sex differences and do studies like this and able looking for the downsides of eating soy? Dr Qi Sun: As a scientist I'm open to any kind of new findings as long as the findings are from well conducted, rigorously designed study. But having said that I couldn't exclude the possibility that maybe soy intake is associated with certain adverse health outcomes, but so far based on my experience I didn't see any such evidence. But having said this I always say I wouldn't risk any possibility, but coming... circling back to the coronary heart disease we really didn't see much difference between men and women. It's true for the younger women we saw a stronger association but for men I also see a lower risk of heart disease. So there's a kind of interesting image on soy intake or isoflavones intake in the United States that people believe they are estrogen so a man shouldn't take it, but if you look at the group of vegetarians, the vegans. There are a lot of guys they practice vegetarian, they practice vegan diets and we also publish on plant-based diet in relation to coronary heart disease and lot of men eat very healthy. And we found those people who practice those kinds of healthy diets, soy is often mouthful of primary sources of proteins and if you look at their risk of developing heart disease, type two diabetes is quite low. Something lower than other normal women who practice otherwise omnivore diet. Dr Carolyn Lam: It's true Qi soy intake could also be a marker of a healthier lifestyle in general, by extension of what you just said. But Mercedes I love that you discuss quite a number of these issues in your editorial and at the end of the day you asked the most important question, what does this mean for us? Should we all be increasing our intake of soy products? Could you give us your synthesis of that? Mercedes Carnethon: Yes, a point that I've definitely tried to make here, and this is really in response to what I expect to be the media fear surrounding new dietary findings. One of the first questions that I know that she and his colleagues will be asked is, should I change my diet? Can I extend my life? And that's because the media is really looking for a lot of sensational headlines in this topic, and I think we have to focus on what we learn from these observational studies. They're a very important step in the scientific process that helps us provide a justification for later clinical trials, that helps us think about the multiple components that work together to promote overall excellent health. And the point you were making right before this about the individuals who eat plant based diets that are heavily based in soy. In the paper it also describes that those individuals exercise more, they may have lower intakes of saturated fat, and so I think ultimately what I take from this at least for myself and for people who would ask is that an overall healthy diet seems to stand up very well in these well done observational studies. And that soy in particular may be a part of an overall healthy diet given what we're seeing here in this very well done study. Dr Carolyn Lam: Oh, that's beautifully put Mercedes and Chi perhaps I can give you the last word. What would you say is the take home message and what are next steps? Dr Qi Sun: I think the core message is this as Mercedes very well discussed, I think soy and especially tofu can be really good components of the overall healthy plant based diet, and by practicing that I think we can significantly reduce the risk of developing coronary heart disease for both men and the women. I think moving forward we would like to see evidence from clinical trials that target cardiometabolic risk factors as outcome, and to see whether increased consumption of tofu and isoflavones can really reduce those risk markers so that they have ample evidence to support the mechanisms. As you mentioned Carolyn that this is an initial study, and it could be soy, intake could be just macro how is it, through clinical trials, we can really control those confounding factors and really provide good evidence to support our findings. Dr Carolyn Lam: Well, in the meantime I just have to say you made my day this is coming from a soy eating vegetarian, so thank you so, so much. Thank you, listeners for joining us today. Dr Greg Hundley: This program is copyright the American Heart Association 2020.  

With Dr Gabriela Kuster & Dr Qian Zhou, University of Basel - Switzerland Link to paper

Gorilla Mode Nitric Pre-Workout is the most potent and comprehensive stimulant free pre-workout on the market in ALL aspects. All angles of saturating the muscle with blood and hydration have been addressed in this formula and are quite literally maxed out. https://youtu.be/iFlmwQXBs6U Gorilla Mode Nitric Supplement Facts Per Full Daily Dose: L-Citrulline – 10,000 mg Creatine Monohydrate – 5000 mg Betaine Anhydrous – 4000 mg GlycerPump™ (65% Glycerol Powder) – 4000 mg Malic Acid – 3000 mg Agmatine Sulfate – 1500 mg Nitrosigine® (inositol-stabilized arginine silicate) – 1500 mg Sodium Nitrate – 1500 mg VasoDrive-AP® (isoleucyl-prolyl-proline (IPP) and valyl-prolyl-proline (VPP) isolated from hydrolyzed milk casein) – 254 mg Gorilla Mode Nitric Vs. Other Pre-Workouts On The Market This is the most maxed out stimulant free pre-workout formula on the market in all aspects. It is also the most comprehensive formula that targets nitric oxide (NO), vasodilation and intracellular hyper-hydration from multiple angles, while maintaining top end dosages across all of those pathways. We completely saturate the traditional Arginine–eNOS–nitric oxide (NO) pathway with a massive 10 gram dose of L-Citrulline, 1.5 grams of Nitrosigine and 1.5 grams of Agmatine Sulfate. The often neglected nitrate–nitrite–nitric oxide (NO) pathway is also topped out with a 1500 mg dose of Sodium Nitrate. A high level of intracellular hyper-hydration is achieved with 5 grams of Creatine Monohydrate, 4 grams of Glycerpump and 4 grams of Betaine Anhydrous. We also addressed the enzyme angiotensin converting enzyme (ACE) with VasoDrive-AP®, which acts as an ACE inhibitor and significantly increases vasodilation.  Finally, we have 3 grams of Malic Acid added in on top of the 10 grams of pure L-Citrulline to act as a Krebs cycle intermediary and counter lactic acid buildup during training. Some of these pathways are so maxed out that we could have easily just chosen one of them and sold the product for $39.99 and still had one of the most potent pre-workouts in the industry. Instead, I packed it all into one absurd product that clocks in with over 30 grams of efficacious active ingredients per full dose. It was incredibly expensive to create, but I am very happy with how it turned out, and I am not exaggerating when I say that this pre-workout is absolutely unmatched. Basically, I just included exactly what I would want to see in a stimulant free pre-workout, even at the obvious detriment of our margins. This product is even more potent than Gorilla Mode when it comes to pure pump and performance. The full daily dose is 2 scoops. Even a half dose (1 scoop) is still far more potent than the majority of other pre-workouts out there at their max dosages. This is another product I wanted to be head and shoulders, clear as day, superior to everything else in the industry. Just like in my description of how Gorilla Mode stacks up to other products in this industry, we can actually back up why our product is better than the rest. When (insert fitness influencer name here) launches their own supplement line, they will regurgitate the same story about how their products are effectively dosed, only use the highest quality ingredients, blah blah blah. They don't even know what they're selling half the time, let alone what combinations of ingredients work synergistically, or how to dose a product properly. They employ others to manufacture their products, or use a pre-made formula their manufacturer uses for every company where they just slap a different label on it and sell it for a huge margin. At the end of the day, most fitness influencers have no idea what goes into making an effective product. They don't know how their products work, they probably wouldn’t even use them if they didn’t sell them, they didn't formulate them, and they have to pay the overhead involved with having a team under them who is responsible for all of that. As you’ve already experienced with Gorilla Mode and Gorilla Mind Nootropics, it is me formulating the products, and they work because I actually put in them what I would want in a product and buy myself if I didn’t have a company. The same applies with Gorilla Mode Nitric. If I didn’t have this product, for an effective stim-free pre-workout I would probably be mixing up 6000-10,000 mg of L-Citrulline for vasodilation (with 6000 mg being the bare minimum of pure L-Citrulline, not Citrulline Malate, and would be dependent on my budget at the time), a saturation dose of Creatine Monohydrate (5000 mg), 3000-4000 mg of Glycerpump to hyper-hydrate the muscle with water, and maybe a quarter teaspoon of Himalayan Pink Salt. The fact that a significant amount of supplement companies will skimp out on Creatine Monohydrate and either not include it at all, or only include a subpar dosage, really sheds light on how scammy this industry can be. That is the cheapest ingredient they could easily dose properly, and even that they won't shell out the money for in their formulas. It’s not hard to put 5 grams of Creatine in a pre-workout, and it is actually pretty cheap to put in there. The reason is, they want you to go buy their creatine product, and will intentionally manipulate their ingredient profile to be deficient in several areas to make you buy more stuff from them. With my products, everything is turnkey. You don’t need to go buy a separate Creatine product from us, you don’t need to stack extra stims on top of our stim-based products, you don’t need to go buy something else to get the max dose of a certain ingredient in any of our formulas, everything you need is in each product at an efficacious dosage. Flavor And Mixability The flavor we chose to start with for Nitric was Mango Peach as it is a more mainstream appealing flavor than Tiger's Blood. Tiger's Blood and a fruit punch flavor will probably be next in the pipeline of flavor releases. Mango Peach is easily a 9 or 10/10 flavor, even for the pickiest of tongues. As there’s such a high concentration of ingredients in this formula we were really happy with how the flavor systems turned out. We were expecting something this potent to be nearly impossible to avoid tasting like ass. Fortunately, that wasn’t the case. It also mixes very well considering the concentration of L-Citrulline, GlycerPump, and all of the other ingredients in this product. There is some grittiness, but that just comes with the territory with putting out a 35 gram serving size product with 10 grams of L-Citrulline and 4 grams of Glycerpump. You will just have to use a bit more water than you would with your standard pre-workout because there are simply more active ingredients in this product that will require more liquid to mix well. How To Dose Gorilla Mode Nitric Mix 1-2 scoops of Gorilla Mode Nitric in 12-14 ounces of water and consume 30 minutes prior to training. Vary the amount of water to achieve your desired flavor level. First time users should begin use with 1/2-1 scoop or less to evaluate tolerance. DO NOT EXCEED 2 SCOOPS IN ANY 24 HOUR PERIOD. Gorilla Mode Nitric Ingredients Breakdown L-Citrulline – 10,000 mg L-Citrulline is the most effective supplement you can use to boost nitric oxide (NO) in the body. Why Nitric Oxide (NO) Is Important Nitric oxide (NO) is made naturally in our bodies and plays a significant role in cardiovascular health. It dilates blood vessels (vasodilation), which lowers blood pressure and increases oxygen in the blood. https://youtu.be/EoYhQIHmKoE Nitric oxide (NO) acts as a messenger to signal blood vessels to dilate, or contract and relax. Sufficient nitric oxide is needed to signal blood vessels to contract or relax to ensure blood is able to flow to and from the heart effectively. Nitric oxide production decreases with age, consequently reducing the elasticity of the cardiovascular system, and impairing the body's ability to ensure sufficient amounts of oxygenated blood are reaching vital organs. Eating enough nitrates and/or supplementing with nitric oxide precursors is very important to ensure that your cardiovascular system maintains optimized function as you get older. In addition, maintaining optimal nitric oxide levels will make you more vascular, allow you to get a much better pump, increase muscle volume, enhance the delivery of oxygen and nutrients to working muscles, support recovery and improve overall physical performance. Increased Muscular Endurance Citrulline has also shown to significantly increase muscular endurance, with one study finding that compared to placebo, a single 8000 mg dose of Citrulline Malate increased the number of reps performed per set, on every set after set 2 [R]. The impact Citrulline had on performance increased the more sets were performed. During the last set performed, the group that took Citrulline had a 52.92% increase in the number of reps they could perform relative to placebo. It also decreased muscle soreness by 40% at 24 and 48 hours after the training session compared to placebo. Effect On Body Composition There isn’t much data on the direct effect Citrulline has on muscle growth and fat loss in humans. However, a rodent model assessed the effect Citrulline had on body composition and found that 20 month old rats that were given a diet that included the human equivalent dose of 160 mg/kg per day for 12 weeks had 13% less body fat and 9% more lean body mass relative to the rats fed a standard diet without Citrulline supplementation [R]. Visceral fat mass was also reduced by 32%. The mortality rate of the rats taking Citrulline was 0%, while the standard diet fed rats had a mortality rate of 20%. L-Citrulline is one of the most promising supplements on the market and has significantly more upside above and beyond its increase in vascularity and pumps in the gym. The Maximum Effective Dose Of L-Citrulline Citrulline is found in watermelons. You would need to eat 1.5 kg of watermelon every day to get 3 grams of L-Citrulline though, which is the minimum effective dose [R]. To get the maximum effective dose of L-Citrulline from your diet, you would need to eat 5.0 kg of watermelon per day to get 10 grams (10,000 mg) of L-Citrulline [R]. Obviously, nobody is going to eat that much watermelon, nor is it a good idea to begin with in my opinion when there are far better ways to allocate your macronutrient/micronutrient intake allotments. This is why L-Citrulline supplementation could actually be worthwhile. The Problem With Citrulline Malate In The Supplement Industry While L-Citrulline is a great supplement to have in your daily regimen, there is a red flag around L-Citrulline supplementation that you need to know about. I'm sure you've seen that some supplements have L-Citrulline in them, and some have Citrulline Malate. Some even say "L-Citrulline Malate". This is a cheap trick companies use to deceive customers. Citrulline Malate is composed of 50% Malic Acid, unless the ratio states otherwise. Authentic Citrulline Malate is produced by chemically bonding free-form L-Citrulline to DL-Malic Acid. When L-Citrulline is chemically bonded to DL-Malic Acid, the end result is Citrulline Malate, which has unique properties. But the problem with the Citrulline Malate in the supplement industry is that it doesn't have this chemical reaction. It's just Citrulline mixed with malic acid in a big mixing vat in the manufacturing facility. There is no chemical bond like there should be to create authentic Citrulline Malate. It's just the two ingredients being mixed together in a cheap blend, and it's sold as "Citrulline Malate", or "L-Citrulline Malate". The reality is that it's just Citrulline stirred up with malic acid. While this isn't a huge deal in itself, the problem lies in the labeling practices companies use to artificially inflate the perceived potency of their product. 6-8 grams is seen as the max clinically proven efficacious dosage in the supplement industry in general. At least, that's what companies will tell you in their marketing. First of all, we already know that the actual maximum efficacious dosage of L-Citrulline is 10 grams per day [R]. In addition, the main issue is that the "L-Citrulline" in their product is actually as low as half of the stated label claim. As mentioned, Citrulline Malate is just a mixture of Citrulline and malic acid. Somehow, companies are getting away with labeling their products with the chemically bonded form Citrulline Malate and claiming they have 6-8 grams per serving in their pre-workout, when they actually just have 3-4 grams of Citrulline and 3-4 grams of malic acid per serving. Instead of labeling the following: L-Citrulline - 3 grams Malic Acid - 3 grams These companies are labeling their products like this: Citrulline Malate - 6 grams Or like this: L-Citrulline Malate - 6 grams Making you think you are getting a high dose, when in reality you are getting the bare minimum efficacious dose per serving of 3 grams. Sometimes, companies will tweak the ratio to be a bit more in favor of a higher Citrulline content relative to malic acid, but this is rarely higher than a 2:1 ratio. So, if you see the following: Citrulline Malate (2:1) - 6 grams That just means that the company has 4 grams of L-Citrulline and 2 grams of malic acid per serving. This is the exact manufacturing process involved in producing the L-Citrulline and "Citrulline Malate" you get in pre-workouts in the supplement industry: As you can see, the Citrulline Malate manufacturing flowchart on the right literally just says, "mix". If this was authentic Citrulline Malate, you wouldn't need to mix L-Citrulline with malic acid, it would be chemically bonded together by the end of the manufacturing process. You're not really getting what you're paying for, and most don't realize this is a tactic in the industry to get better margins and artificially inflate a products perceived efficacy. Even if a pre-workout had what on paper appears to be a top end efficacious dose of 8 grams per serving, how much L-Citrulline are you actually getting out of that serving? 4-6 grams at most. I have yet to see a pre-workout formula actually hit a top end L-Citrulline dosage, and of the ones that get close, they use Citrulline Malate to inflate their label. In addition, even if you had the bonded version (which supplements don't), reacted Citrulline Malate will break apart into L-Citrulline and malic acid right away after its mixed in water. It's all just a trick to artificially inflate a products perceived potency on a label, as each ingredient should be listed separately. Most supplements have malic acid anyways in the "other ingredients" section, which is still an active ingredient that does have some potential performance benefits that you would get from the “Malate” portion of Citrulline Malate. L-Citrulline and malic acid work via a different mechanism of action. Citrulline bypasses the liver and gets converted to arginine, which increases NO levels in the body. Malic acid is a Krebs cycle intermediary that counters lactic acid buildup. How much do you need of each though? With Citrulline, we know where the top end data lies. Malic acid, we don't. There is research on Citrulline and Citrulline Malate, but not much data on supplementing with malic acid to replenish depleted levels as a Krebs cycle intermediary. I don't think we can make a generalized overview on how effective the malic acid component was in the Citrulline Malate research either because we can't determine if the results were derived from the malic acid, the L-Citrulline, or both. Considering this, I included an additional 3000 mg of malic acid separately in the Gorilla Mode Nitric formula as an active ingredient in the main ingredients panel. As mentioned, malic acid is most commonly used as a filler in supplements, and will be found in small amounts in many product "other ingredients" sections. The only other time it is used is by companies artificially inflating their perceived L-Citrulline dosage via Citrulline Malate. No companies are including a maxed out dose of pure L-Citrulline as well as malic acid separetely though. It is always a subpar amount of each. So, if there is some sort of performance enhancing benefit to having a high dose of malic acid, you are also getting it via Nitric on top of the maximum efficacious 10,000 mg dose of pure L-Citrulline. At the end of the day, for vasodilation you should concern yourself with is how much pure L-Citrulline is in your pre-workout supplement. I have yet to see a product with more than 6000 mg of PURE L-Citrulline. I have only seen a handful of products with 6 grams of L-Citrulline, and another handful of products with 8 grams of Citrulline Malate (which only yields 4-5 grams of actual L-Citrulline, with the remainder as malic acid). I put 10 grams of PURE L-Citrulline in Gorilla Mode Nitric, as well as 3 grams of malic acid separately, so you can get the full benefits of the max dosage of each ingredient and transparently see exactly what you are actually getting in the product. Even if you decide to only use a half dose of this product you will still get 5000 mg of pure L-Citrulline, and the formula is still top notch even when cut in half. Citrulline Vs Arginine One of the most well-known pump ingredients is Arginine. The problem with L-Arginine is that it is very ineffective at increasing Nitric Oxide synthesis. Logically, you would assume that taking Arginine would be the most effective way to increase Arginine levels in the body. However, this is not the case. Oral L-Arginine is taken up and metabolized by the liver so much that it does not actually effectively increase Arginine levels, and it may even be unsafe to use because of how much excessive urea it yields [R]. L-Citrulline bypasses the liver and passes freely to the kidneys where it is metabolized to Arginine [R]. The most effective supplement that can be used to increase Arginine levels in the body to improve cardiovascular and metabolic health outcomes is L-Citrulline [R]. L-Citrulline supplementation has shown to lower blood pressure and provide atherogenic-endothelial protection [R]. When it comes to NO precursors that significantly improve pumps, nothing beats an efficacious dose of pure L-Citrulline. Creatine Monohydrate – 5000 mg Creatine is the best studied and most effective performance enhancing supplement outside of exogenous hormones and drugs. Creatine’s Effect On Muscle Size And Strength Supplementing with creatine has shown time and time again to significantly improve strength, power output and muscle size [R]. Creatine’s effect on strength is facilitated by increasing the body’s stores of phosphocreatine, which is then used during high intensity exercise to produce ATP [R, R]. Creatine’s effect on muscle size is facilitated by drawing water into the muscle via osmosis, consequently increasing body weight and muscle size. In addition, with the increased strength creatine provides, heavier weights can be used in the gym which provide more stimulus for growth, consequently increasing muscle accrual in the long-term. Creatine supplementation also appears to increase the number of myonuclei that satellite cells will donate to damaged muscle fibers, which increases the potential for growth of those fibers [R]. A typical omnivorous diet provides about 1 gram of creatine per day, which isn’t enough to get the benefits you would from supplementation, and also isn’t nearly enough to support health status and methylation in those with genetic polymorphisms. Creatine’s Effect On Methylation And Health Status About 1 gram of creatine is endogenously produced in the body naturally in young healthy adults [R]. Most of the human body's total creatine and phosphocreatine stores are found in skeletal muscle, while the remainder is distributed in the blood, brain, and other tissues [R]. While there are a host of processes in the body that rely on creatine to be carried out optimally (and are often completely neglected), one of the most notable functions of creatine is neurological support [R]. In addition, the endogenous synthesis of creatine relies on a process called methylation. Arginine and Glycine are combined by an enzyme to form guanidinoacetate, which is then methylated into creatine. The problem is that this process is dependent on a mechanism of action that is commonly inhibited in the general population via endogenous Arginine deficiency, Glycine deficiency, or MTHFR polymorphisms. The MTHFR gene codes for an enzyme called methylenetetrahydrofolate reductase or MTHFR. This enzyme is needed for the production of DNA and methylation pathways that are essential for all bodily functions. Genetic variations in this gene results in reduced activity of the enzyme and has been associated with cardiovascular disease, neurological defects, some forms of cancer, and a myriad of other diseases and disorders [R, R]. Personally, I am homozygous for C677T of MTHFR, which results in a 80-90% decrease in my efficiency in processing folic acid. The direct reflection of that in blood biomarkers can be high homocysteine and low B12 and folate levels. I determined this via a simple 23andMe genetics test. Upwards of 45% of your body’s methylation demands are used to synthesize creatine. For someone with a MTHFR polymorphism, you can put a significant amount of stress on your methylation pathway and deplete far more methyl groups than you should be just to create the 1 gram per day that you endogenously synthesize. We lose up to 2-3 grams of creatine per day because it converts to creatinine and is then passed out of the body via urine. As you can see, adequate replenishment of creatine is probably not being accomplished if you aren’t consistently eating a fair bit of meat or fish. And for those with impaired methylation pathways, supplementing with exogenous creatine is likely the only way creatine replenishment can be achieved. One study found that supplementing with 5 grams of creatine per day lowered plasma homocysteine levels by almost 50% in the subject who is homozygous for C677T of MTHFR [R]. Creatine supplementation can significantly lower the body’s demands for methylation and prevent the depletion of methyl groups. This is why I personally supplement with 5 grams of creatine per day. Do You Need To Cycle Off Of Creatine? No, you do not need to cycle off of creatine. Your body does not get used to it, and long-term use has shown to be safe in healthy adults [R]. Betaine Anhydrous – 4000 mg Betaine, also called Trimethylglycine, acts as a methyl donor and an osmolyte in the body. Earlier in the creatine breakdown, I briefly outlined the importance of having a sufficient amount of methyl donors available for methylation processes in the body, including the endogenous synthesis of creatine. For some individuals (depending on PEMT gene variations) Betaine can substitute for folate and B12 in the regeneration of methionine and can be choline sparing via this mechanism. It can also provide additional needed methyl donors when over-depletion occurs in genetically predisposed individuals that do not supplement with creatine, or have other deficiencies. As an osmolyte, Betaine helps balance fluid levels inside and outside of cells. The main reason I included Betaine in this formula is for its ability to induce intracellular hyper-hydration. By improving hydration status in cells, Betaine increases the pump you get in the gym, and can help prevent dehydration during exercise. Research has also shown that Betaine supplementation may reduce the risk of cardiovascular disease, as well as improve digestion and liver function [R, R, R, R]. In a performance enhancing context, Betaine supplementation has also shown to increase power, endurance, muscle growth and fat loss [R, R, R]. How significant will this effect on body composition be in practical application? Negligible in my honest opinion, but the enhanced pump made this ingredient worthwhile to add into the formula. GlycerPump™ (65% Glycerol Powder) – 4000 mg Glycerol significantly enhances pumps and performance by hyper-hydrating the muscle with water. Glycerol’s Effect On Hydration, Pumps And Endurance If you drink a lot of water with nothing else in hopes of hyper-hydrating your muscles, the fall in osmolarity in your body stimulates the kidneys to remove most of the excess water within an hour. If you add glycerol to the water, this prevents the drop in osmolarity and can extend the hyper-hydration of your muscles by up to four hours. By adding Glycerol to your pre-workout, you can hold upwards of an extra liter of water via this hyper-hydrating effect. Hydration is one of the most critical factors when it comes to performance. Aside from massive pumps, Glycerol use has shown to increase endurance by as much as 24%, as well as improve aerobic and anaerobic power and performance [R, R]. Only a 2% loss in fluids can result in as much as a 20% decrease in exercise performance. GlycerPump™ Vs Other Forms Of Glycerol We chose the trademarked GlycerPump because it doesn’t clump up nearly as much as other forms of Glycerol powder and it’s more stable. Glycerol is normally a liquid at standard temperature and pressure, and many supplement companies have attempted to create a powder form of Glycerol that is stable. Glycerol products get clumpy, have horrible viscosity and have a short shelf life. Because of this, most companies avoid this ingredient entirely, as it can cause severe clumping within just a couple months of being manufactured. Regular glycerol containing products only yield as low as 10% glycerol, which makes them ineffective, and higher yielding glycerol products can be unstable within complex formulas like ours and result in a clumpy product, or complete product failure. GlycerPump™ is created using unique spray drying technology, yielding a stable powder form of glycerol standardized to 65%. It is MUCH better than other alternatives and won't result in the powder turning into a rock. Keep in mind, while it is manageable, this is not a clump-free product, and there’s nothing I could do about that if I wanted to include the high concentration of ingredients that I did in Gorilla Mode Nitric. Store Gorilla Mode Nitric in a cool dry place, and if it clumps, that’s just what comes with the territory with a product dosed like this. If it clumps, just get out a knife or spoon and chop it up, and it will still mix fine once it hits the water in your cup. Agmatine Sulfate – 1500 mg Agmatine has shown to induce NO production via the same processes as arginine, but does it far more effectively [R]. This results in even bigger pumps in the gym and improved overall performance. Agmatine has also shown to be neuroprotective against excitotoxicity and stroke, and also has anti-anxiety and anti-depressant effects that may enhance state of well-being and mood elevation with supplementation. Agmatine has also shown to manipulate pain receptors, which may result in an increased pain tolerance during intense training. Agmatine is a very misunderstood compound and is believed by some to antagonize other vasodilators. Agmatine works in a more selective way than other vasodilators, as it only increases one of the three Nitric oxide synthase (NOS) isoforms. It also decreases the other two NOS isoforms, which is where the hypothesis about it being vasoconstricting was raised as a legitimate concern. The three NOS isoforms include iNOS, nNOS and eNOS. They each play their own role in certain tissues to regulate vasodilation. iNOS (inducible) produces high concentrations of NO via an immune system response to kill harmful bacteria. In excess, iNOS can be inflammatory. nNOS (neuronal) regulates neurological health and facilitates communication in the brain across neurons. In excess, nNOS can inhibit the growth and repair of neurons. eNOS (endothelial) facilitates vasodilation in the lining of blood vessels to improve blood flow. eNOS is the main isoform that most are familiar with that increases blood flow and lowers blood pressure. It is also the main isoform that facilitates massive pumps in the gym. While NO is great for the gym and vascular health, it can be inflammatory in excess. NO production by eNOS has shown to play a protective role in cerebral ischemia by maintaining vascular permeability, whereas NO derived from nNOS and iNOS is neurotoxic and can enhance the neuronal damage occurring in ischemia [R]. This is where the selective activity of Agmatine shines, as data suggests that Agmatine's mechanism of action is facilitated by inhibiting iNOS and nNOS and increasing eNOS [R, R]. Agmatine has shown to selectively increase eNOS levels while simultaneously decreasing iNOS and MMP-9 protein expression [R, R]. Anecdotally, Agmatine does not seem to inhibit any of the positive effects of L-Citrulline or other vasodilators. On the contrary, it seems to complement other "pump" compounds very effectively. On paper, Agmatine sounds like the perfect ancillary compound to add to a pre-workout as it increases expression of the NOS isoform we want, while simultaneously inhibiting the isoforms that can be more inflammatory in excess. Nitrosigine® (inositol-stabilized arginine silicate) – 1500 mg Nitrosigine got some hype behind it when independent researchers from the University of Arkansas presented data suggesting that 1500 mg of Nitrosigine was almost as effective as 8000 mg of Citrulline Malate 2:1 (5333.33 mg L-Citrulline and 2666.66 mg Malic Acid) at increasing flow mediated dilation (FMD) [R]. FMD refers to dilation of an artery when blood flow increases in that artery. Because the primary cause of FMD is release of nitric oxide by endothelial cells, we can use FMD as a proxy for NO levels. To circumvent the lackluster efficacy of plain oral Arginine, Nutrition 21 (the developers of Nitrosigine) created a complex of bonded arginine and silicon. The inositol acts as a stabilizer and increases the bioavailability of the complex, consequently resulting in a potent NO boosting compound. Remember that the main issue with Arginine is poor bioavailability. The inositol stabilizer helps circumvent that issue [R]. Unlike plain Arginine, Inositol-stabilized Arginine silicate (Nitrosigine) has shown to kick in within 15 minutes and elevate blood Arginine levels for up to six hours after ingestion [R, R]. Nitrosigine has some impressive data reinforcing its efficacy, and it is purported to be much more effective milligram for milligram than other common vasodilators at increasing NO levels. On top of the increase in vasodilation and pumps, the developers claim that after a single dose Nitrosigine can increase mental acuity and focus by 33% within 15 minutes, with a compounding effect over time. In addition, they claim that Nitrosigine supports enhanced recovery by reducing markers of muscle damage [R]. Nitrosigine Vs. L-Citrulline Vs. Agmatine Sulfate In Vitro An in vitro study was designed by Nutrition 21 to compare the cellular production of NO of several sports nutrition ingredients. These ingredients included Nitrosigine, L-Arginine, L-Arginine AKG, L-Citrulline, Citrulline Malate and Agmatine Sulfate. Nitrosigine was dosed at a concentration of 1.0 g/L. Cell culture concentrations of the other compounds were dosed relative to a 1500 mg dose of Nitrosigine using the following doses: L-Arginine - 1500 mg L-Arginine AKG - 4000 mg L-Citrulline - 3000 mg L-Citrulline Malate - 3000 mg Agmatine Sulfate - 1000 mg As NO is unstable and rapidly converts to nitrites or nitrates, nitrite levels were measured as a proxy for NO production. At the doses used in this study, Nitrosigine significantly increased NO production over each of the five other compounds tested. There was a greater than 5X increase in NO production with Nitrosigine compared to the other tested vasodilators. In addition, of the compounds tested, only Nitrosigine significantly increased NO production versus control. While this looks very impressive for Nitrosigine, you have to consider that this is an in vitro study conducted by Nutrition 21 themselves. The results basically indicate that every single clinically proven vasodilator that we know works is useless as it couldn't increase NO production above control, meanwhile Nitrosigine somehow cranked it through the roof over 5x higher than the rest. While the results are certainly interesting, I would take this data with a grain of salt. Nitrosigine Vs. Citrulline Malate - Vasodilation Study On Young Adults Unlike the in vitro study comparing Nitrosigine to Citrulline Malate, another study in 2019 was apparently conducted independently from the company without their knowledge whatsoever [R]. This study was conducted on young, healthy, physically active adults, and provides more acceptable parameters for us to take seriously when it comes to evaluating Nitrosigine's efficacy in humans relative to a decent dose of the most widely used vasodilator in the industry, Citrulline Malate (assuming that the study was actually unbiased as is implied) [R]. 16 healthy young men and 8 healthy young women participated in the study. Each subject either received 1500 mg of Nitrosigine, 8000 mg of Citrulline Malate 2:1, or dextrose placebo. Keep in mind, this is Citrulline Malate 2:1, so the subjects are only actually getting 5333.33 mg of L-Citrulline. The study was randomized, double-blind, within-subjects design where participants reported for three trials, each preceded by a 7-day washout period. Baseline flow mediated dilation (FMD) measurement was obtained for each visit, followed by consumption of one clinical dose Citrulline Malate (8 grams), Nitrosigine (1.5 grams), or dextrose placebo (8 g). Following a 60-min digestion period, FMD was repeated. Supplementation order was randomized controlling for potential order effects. Basically, the subjects would show up, get their FMD evaluated, take one of the three options, and then get their FMD checked again to see how well the random compound they ingested increased their NO production. They would then take a week off, and come back and repeat, where they would then receive one of the remaining two compounds, with the same measurement process. This would be followed by another week off, and then a third visit where the subjects would receive whatever the third ingredient was that they hadn't yet tried, and the same measurement process was conducted. Nobody knew what they were ingesting during each trip, but by the end of the experiment every single subject had tried each ingredient, and their vasodilation response was evaluated for comparisons. Expectedly, Citrulline Malate and Nitrosigine yielded a greater improvement in FMD response than placebo. Citrulline Malate increased FMD by 34%. Nitrosigine increased FMD by 31%. Placebo decreased FMD by 2%. Allometric scaling of the FMD values was required afterwards to adjust the results to account for the body size of males relative to females. After allometric scaling of the FMD values, Citrulline Malate was shown to increase FMD by 25%, Nitrosigine increased FMD by 23%, and placebo increased FMD by 0.6%. Clearly Citrulline Malate isn't as useless as the Nutrition 21 funded in vitro data would lead you to believe. The results from this study suggest that the clinically efficacious 1500 mg dose of Nitrosigine is almost equally effective to 5333.33 mg of L-Citrulline mixed with 2666.66 mg of Malic Acid. Clearly Nitrosigine has a lot of promise as a pre-workout ingredient, which is why I included it in our formula alongside the massive dosages of other potent vasodilators we already have. Every single effective vasodilator we felt was worthwhile is in here at topped out dosages. While it would be nice if there was data we could refer to evaluating if there is a synergy between Nitrosigine and Citrulline, or Nitrosigine and Agmatine, regardless if the end result is 1+1 = 2 or if it's 1+1 = 3, my goal was to make sure this formula was air tight and ensure you are getting the maximum possible performance enhancing benefit from each and every ingredient. Sodium Nitrate – 1500 mg Sodium is one of the most critical and overlooked components of a diet designed to optimize exercise performance. But, keep in mind, you’re not going to get enough sodium in a pre-workout without it tasting terrible. Other companies will put a tiny dose of sodium in their product and then claim you will get all of the benefits of it. Personally, I just toss and wash a quarter teaspoon of a high quality salt 30 minutes pre-workout with Gorilla Mode or Gorilla Mode Nitric, and I take another quarter teaspoon with my post-workout drink. The reason I included sodium nitrate in Gorilla Mode Nitric is not for the sodium, it is for the nitrates. The nitrate–nitrite–nitric oxide (NO) pathway is a series of oxygen-independent and NO synthase–independent single-electron transfer reactions that ultimately facilitate vasodilation. The traditional Arginine–eNOS–nitric oxide (NO) pathway is what most NO precursors focus on. The nitrate–nitrite–nitric oxide (NO) pathway often goes completely neglected though, and is another pathway we can leverage to amplify NO levels to an even greater level. Nitrates found in food can be converted into nitrites in the body, and then reduced to NO via nitrite reductase [R]. Several studies have shown that nitrate supplementation can increase plasma nitrite concentrations, and consequently Nitric Oxide, which then enhances pumps, endurance, and all of the other benefits we use NO precursors for [R]. Nitrate Dosage - Sodium Nitrate Vs. Beet Root Powder Pre-Workouts Beet root is a very popular ingredient that has started to get a lot of attention over the past few years. The reason why beet root works is because it is a densely concentrated source of nitrates. However, despite it being densely concentrated relative to other foods, beet root still only contains 1-2 percent of nitrates per gram of raw material. This would require you to ingest an absurdly high amount of beet root to get the same amount of nitrates that you can get from the 1500 mg of sodium nitrate in Gorilla Mode Nitric. To put it in perspective, your standard beet root powder pre-workout supplement has around 4.3 grams of Beet root juice powder in it. The amount of nitrates in that 4.3 grams is about 43 mg. That means that you would need to chug the entire tub at one time to get the same amount of nitrate as you would get out of a 1500 mg dose of sodium nitrate. There is no feasible way to get a high dose of nitrates from beet root powder without ingesting massive quantities far higher than what you would get in a dietary supplement. By weight, sodium nitrate is the most highly concentrated source of nitrates among any dietary ingredient. Nitrates comprise 73 percent of the total weight of sodium nitrate [R]. The optimal dosage of nitrate supplementation appears to be between 6.4-12.8 mg/kg [R]. That equates to the following dosage protocols: 440-870 mg for a 150 lb person 580-1,160 mg for a 200 lb person 730-1,450 mg for a 250 lb person For every gram of sodium nitrate, 730 mg is from nitrate. The 1.5 grams of sodium nitrate in Gorilla Mode Nitric yields 1095 mg of nitrate. There are other nitrate based supplements in the industry like Arginine Nitrate, Creatine Nitrate, Betaine Nitrate that operate via this same nitrate–nitrite–nitric oxide (NO) pathway, however, none of them have as high of a nitrate composition gram for gram as Sodium Nitrate does. VasoDrive-AP® (isoleucyl-prolyl-proline (IPP) and valyl-prolyl-proline (VPP) isolated from hydrolyzed milk casein) – 254 mg VasoDrive-AP consists of 2 lactotripeptides: isoleucyl-prolyl-proline (IPP) and valyl-prolyl-proline (VPP) which are clinically proven to inhibit Angiotensin converting enzyme (ACE) and significantly increases vasodilation.  Angiotensin converting enzyme (ACE) controls blood pressure by regulating the volume of fluids in the body. ACE facilitates this process by converting the hormone angiotensin I to the active vasoconstrictor angiotensin II. Angiotensin converting enzyme inhibitors (ACE inhibitors) inhibit ACE, consequently reducing angiotensin II production. Reducing angiotensin II results in the dilation of blood vessels and a reduction of blood pressure. Bradykinin is also a vasodilator in the body that is degraded by ACE. Clinical data suggests that individuals who genetically have lower levels of ACE respond better to training and are at an advantage in endurance sporting events [R, R]. The more blood flow you have, presumably the more oxygen and nutrient carrying capacity you will have during exercise. VasoDrive-AP has shown in 30 clinical studies to date a potent effect on vasodilation and blood pressure reduction via this mechanism completely independent from the traditional Arginine–eNOS–nitric oxide (NO) pathway [R].  Ingredients I Didn’t Include In The Formula And Why Vitamin C Vitamin C is a very potent antioxidant and plays a crucial role in lowering blood pressure and regulating health blood flow. Supplementing a Vitamin C deficient diet can be very beneficial, except when you're dosing it pre-workout. Vitamin C is inexpensive and has tons of clinical data to back its efficacy, so it is often thrown in pre-workouts. The problem with this is that using Vitamin C pre-workout can blunt the hormetic response to the workout itself and hinder your results [R]. The point of working out is to damage the muscle, which then results in the body signaling repair processes to start that will help you recover and ultimately get bigger and stronger to adapt to the workload. If you manually decrease that hormetic response to exercise by ingesting Vitamin C pre-workout, you will reduce the damage done and ultimately prevent your body from stimulating as much growth. Personally, I don't take any vitamins, anti inflammatories, or powerful antioxidants for several hours before or after my workout to be safe. Antioxidants And Vitamins As mentioned, one of the worst things you can do is take antioxidants before your workout. The stress and damage induced by weightlifting or exercise is needed to facilitate muscular recovery and progress. The reactive oxygen species and inflammation produced during intense training assists with that process, and is also why drugs like Ibuprofen can inhibit muscle growth so severely. The inflammatory response to training is what we want in order to recover, and by inhibiting that with antioxidants, vitamins or anti-inflammatory drugs, you prevent your body from breaking down and recovering the way it needs to in order to grow [R, R]. A pre-workout formula with a bunch of vitamins and antioxidants in it is more likely to hinder your gains than help. Potassium I advise reaching your recommended daily intake of 4,700 mg through diet rather than through supplementation. It is not legal to sell Potassium in high amounts, and you will usually find that supplements have no more than 100 mg or so per serving because of this. For this same reason, supplementation isn't cost effective, and pre-workouts with potassium in them are including it solely to claim the benefits of potassium all the while knowing the dose in their product is next to useless. The amount of potassium in pre-workout supplements does next to nothing for you when it comes to helping you hit the RDA. S7™ S7™ is a blend of green coffee bean extract, green tea extract, turmeric extract, tart cherry, blueberry, broccoli and kale that has gotten some hype in pre-workouts recently. I was considering including it in our formula until I saw that the blend was comprised entirely of potent antioxidants and anti-inflammatories. Turmeric is one of the most potent anti-inflammatory spices known to man, which is why it also shows such therapeutic promise via supplementation. However, the last thing you want to use pre-workout is a potent anti-inflammatory compound. Inflammation is what we are striving for during a workout, and using anything that significantly impairs this inflammatory response to training is something that should not be used pre-workout, and should be saved for taking far away from the peri-workout window. Beta Alanine Beta Alanine is the ingredient that makes your skin itchy and has you sitting there scratching your face between sets. I assume it is included in pre-workouts because you can blatantly feel something when you take it, so people associate feeling something with the product being potent. Personally, I can’t stand the itchy skin effect it has, and it can be bad enough that it ruins a pre-workout just based on that. In addition, it doesn’t have more than a negligible effect on performance at best. Acute sporadic bumps in Beta Alanine will do next to nothing if you are only getting your Beta Alanine dosage from your pre workout supplement a few times per week. If you were to take it correctly, dosing it multiple times per day, for weeks on end, at a high enough dosage, the impact on performance is notable, although still fairly insignificant at the end of the day. “The median effect of β-alanine supplementation is a 2.85% (-0.37 to 10.49%) improvement in the outcome of an exercise measure, when a median total of 179 g of β-alanine is supplemented” [R]. 179 grams (an amount nobody would end up getting in) for a 2.85% improvement in performance, and a ton of itchiness… “Although some laboratory-based studies show an ergogenic effect with beta-alanine supplementation, there is a lack of field-based research in training and competition settings.” “There was an unclear effect (0.4%; ± 0.8%, mean, ± 90% confidence limits) of beta-alanine on competition performance compared to placebo with no meaningful changes in blood chemistry. While there was a transient improvement on training performance after 4 weeks with beta-alanine (-1.3%; ± 1.0%), there was an unclear effect at ten weeks (-0.2%; ± 1.5%) and no meaningful changes in blood chemistry. Beta-alanine supplementation appears to have minimal effect on swimming performance in non-laboratory controlled real-world training and competition settings” [R]. Leucine Taking Leucine post-workout promotes muscle growth. However, taking Leucine in your pre-workout has shown to diminish muscular performance via the inhibition of glycogen to glucose conversion within muscle cells and insulin signaling. On top of that, Leucine can prevent the uptake of Tyrosine into the brain, consequently inhibiting dopamine production, which is the opposite of what we are trying to accomplish pre-workout. Should You Ever Cycle Off Of Gorilla Mode Nitric? Despite Nitric being stimulant free, I would still advise cycling your use of Gorilla Mode Nitric every once in a while. In general, I advise cycling your use of any supplement that isn't being used daily to replace a dietary deficiency. Interfering with balancing mechanisms in the body chronically long-term is almost always going to build up to some unintended negative side effect, and redlining your Nitric Oxide levels and vasodilation on a daily basis for long uninterrupted spans of time will probably be no different. How often you cycle it is ultimately up to your discretion as there is no tolerance build up with the ingredients in Nitric, and some of them actually have accumulative benefits. Personally, I use pre-workouts 4 days per week because I workout 4 times per week. Every month or two I will also take a full week off of everything except for my daily health supplements. How To Combine Gorilla Mode Nitric With Gorilla Mind Rush Gorilla Mode Nitric has no stimulants in it, so if you want the most potent combination of performance, energy, focus and drive pre-workout you can combine Nitric with Gorilla Mind Rush. Dose each product as you would normally dose them on their own, as there is no overlap between the two formulas. How To Combine Gorilla Mode Nitric With Gorilla Mode Gorilla Mode can be combined with Gorilla Mode Nitric to achieve a more middle road level of stimulants but with the maxed out vasodilation and hyper-hydration. The instance in which mixing the two would make the most sense is if you don't want to use a high dose of Gorilla Mode because the stimulant dosages are higher than you prefer or can tolerate, but still want to max out the benefits of the ingredients included for pump and performance. For example, if 2 scoops of Gorilla Mode contains too high of a dose of stimulants for you, you could use 1 scoop of Gorilla Mode with 1 scoop of Gorilla Mode Nitric. Or, a 1/2 scoop of Gorilla Mode with 1.5 scoops of Gorilla Mode Nitric. Alternatively, if you are using Nitric and want a little bump of stimulants but are too sensitive to the stimulant complex in Gorilla Mind Rush, then you might want to add a bit of Gorilla Mode to your Nitric dose as the blend of stimulants in Mode is a notch less aggressive than the stimulants in Rush. Mix and match at your own discretion based on your own stimulant tolerance and exactly what you are looking to get out of your pre-workout. Personally, I love combining Rush and Nitric pre-workout. Sometimes I will use Mode with Nitric instead though as the Kanna and N-Phenethyl Dimethylamine Citrate hits differently than the stimulants in Rush. It all depends on what I'm training, how well rested I am, and the effects I am shooting for. Conclusion - What To Expect From Gorilla Mode Nitric In general, you can expect a massive increase in nitric oxide (NO) levels, vasodilation, intracellular hydration and as significant of a boost in muscle strength and endurance as you can get from a legal non-hormonal pre-workout. This product is maxed out from all angles. The traditional Arginine–eNOS–nitric oxide (NO) pathway is completely saturated with an unheard of dose of L-Citrulline, as well as topped out doses of Nitrosigine and Agmatine Sulfate for good measure. Over a gram of nitrates also ensures that the nitrate–nitrite–nitric oxide (NO) pathway is taken care of. Intracellular hyper-hydration is best-in-class too with a huge dose of Creatine Monohydrate, Glycerpump and Betaine Anhydrous to volumize the muscle and support performance and pumps. Inhibiting the enzyme angiotensin converting enzyme (ACE) with a clinical dose of VasoDrive-AP® also checks off another pathway to push the boundaries on supraphysiological levels of vasodilation.  Finally, a high dose of Malic Acid was included for good measure to act as a Krebs cycle intermediary and support greater levels of muscular endurance. Try Gorilla Mode Nitric for yourself here and let me know what you think.

Emerging information about how SARS-CoV-2 virus infects cells has led to speculation that NSAIDs and ACE inhibitors/angiotensin receptor blockers (ARBs) may worsen clinical disease. Infectious disease physician Carlos del Rio, MD, of Emory University explains the concerns and their clinical implications.

Emerging information about how SARS-CoV-2 virus infects cells has led to speculation that NSAIDs and ACE inhibitors/angiotensin receptor blockers (ARBs) may worsen clinical disease. Infectious disease physician Carlos del Rio, MD, of Emory University explains the concerns and their clinical implications.

Strap yourselves in for a wild biohacking ride full of new biohacks—some of which I hadn't even heard of. My guest on today's podcast is named Marc. That's it. That's the only information I'll release about his identity. He started his career in investment banking and financing renewable energies and now arranges financing for various government projects—from hydro dams, to farms, to airports—and is now heavily immersed in the fields of biohacking and researching emerging health-enhancing technologies, primarily inspired by managing an incurable genetic defect in his kidneys. In this podcast, we delve into a host of new biohacking technologies you've probably never heard of, from NAD boosters, to stem cell enhancing protocols, to longevity and anti-aging molecules, and much more! During this discussion, you'll discover: -How Marc got interested in these biohacks...8:03 Doing due diligence for banking investments revealed a lot of flaws in technologies such as solar and wind power Became a trusted voice among his partners and investors due to his findings -Biohack #1: How to change the gravitational pull inside your cells to speed up the healing process...11:38 Marc was diagnosed w/ polycystic kidney disease (PKD) Defective on PK-1 protein; cysts develop on the kidney Standard medicine considers it incurable Began ketogenic diet (low glucose slows the growth of the cysts) Increase in klotho protein halts the disease Changes the gravitational pull inside the cells, thus changing the time perspective in which they can heal (40 hrs of healing w/in a 24 hr timeframe) Very expensive: ~$2500/month Extremely detail-oriented protocol Use olive oil or yogurt as a precursor approx. 3-4 days before ingesting How the klotho protein is activated and suppressed Psychological stress, inflammation, oxidative stress and depression mitigate its production Angiotensin decreases klotho , insulin, exercise (resistance training), cordyceps, ginseng extract, activated charcoal increase klotho Vitamin D transport system activates immune system Nagalase enzyme suppresses the immune system by suppressing immune cells GcMAF mitigates damage done by nagalase -Ways to protect from harmful 5G technology...32:15 EMF doesn't actually attack human DNA; it attacks and changes the DNA of the gut microbiome, with an effect on the brain can withstand 5G -The skinny on V-cells...44:30 V-cells are totipotent cells Different types of cells: Totipotent cells can become any type of cell (the crème de la crème of stem cells) Pluripotent can be a variety of different cells Multipotent cells, less variety Singular potent - only one type of cell Embryonic-like stem cells "Non-activated"—dormant, body doesn't know what to do with them Device in the works to increase bioavailability of V-cells High-frequency pulse laser Very small margin of error for it to be efficacious BGF podcasts mentioned: Increased exercise and caloric restriction will mobilize small v-cells -A mostly unknown way to boost NAD levels...58:02 Change the environment so that cells produce NAD sans precursors (such as nicotinamide riboside, NR) increase of 242% NAD+ is used by the body, then converted into NR This becomes downregulated w/ age for boosting NAD -A natural way to upregulate endothelial stem cells...1:03:55 Beta-glucans in mushrooms -Interesting biohacks related to water...1:07:42 (code: GREENFIELD) (code: GREENFIELD) (code: GREENFIELD) Hydrogen is very dangerous; use it with caution when drinking hydrogen-enriched water -A device that increases the mineral density of plants...1:18:03 Lab-grown Placed close to organism w/ water, allows water to come back to its original structure Pesticides are not necessary Water becomes 100% coherent Water and Wellness deuterium-depleted water -And much more... Resources from this episode: - - - - - - - (code: BEN) - -Book: -Book: - for boosting NAD - (code: GREENFIELD) - (code: GREENFIELD) - - - (code: GREENFIELD) - - -BGF podcasts mentioned: Episode sponsors: -Boundless: -: The Challenge starts January 6th, it's completely FREE to join, and when you do you'll get a bunch of exclusive content including access to a Q&A by yours truly answering all your burning fasting questions. To join just go to getkion.com/fasting -: A formulation of 24 unique strains, each of which included at their clinically verified dose, to deliver systemic benefits in the body. Save 15% off your order when you use discount code: BEN15 -: kApex breaks down the fats you eat into fatty acids, which allows you to increase the fatty acid oxidation inside your mitochondria both in your muscle and liver. Get 20% off your order when you use coupon code: GREENFIELDKX -: I’ve been using Four Sigmatic products for a while now and I’m impressed by the efficacies of their mushroom products. I use them. I like them. I support the mission! Receive 15% off your Four Sigmatic purchase when you use discount code: BENGREENFIELD Do you have questions, thoughts or feedback for my secret podcast guest or me? Leave your comments below and one of us will reply!

Juan José Gómez Doblas entrevista a Julio Núñez Villota (Unidad Insuficiencia Cardiaca del Hospital Clínic Universitari de València) sobre las principales conclusiones que ofrecen dos subestudios del efecto de sacubitrilo/valsartán en IC presentados en AHA 2019: Effects of Sacubitril/Valsartan in Women y Angiotensin-neprilysin inhibition inheart failure across the spectrum of ejection fraction.

In this podcast, Dr. Carl Dean, a Nephrologist with Kidney Specialists of Minnesota, presented at Ridgeview Medical Center's Live Friday CME Series on September 27th, 2019. At this event, Dr. Dean provided information on acute kidney injury (AKI)- its frequency, management, and treatment modalities available for AKI. Enjoy the podcast! Objectives:    Upon completion of this podcast, participants should be able to: Evaluate for the cause of acute kidney injury. Describe when a referral to a nephrologist is warranted. Identify treatment options available for acute kidney injury. CME credit is only offered to Ridgeview Providers for this podcast activity. Complete and submit the online evaluation form, after viewing the activity.  Upon successful completion of the evaluation, you will be e-mailed a certificate of completion within 2 weeks.  You may contact the accredited provider with questions regarding this program at  rmccredentialing@ridgeviewmedical.org. Click on the following link for your CME credit: CME Evaluation: "Approach to Acute Kidney Injury" (**If you are listening to the podcasts through iTunes on your laptop or desktop, it is not possible to link directly with the CME Evaluation for unclear reasons. We are trying to remedy this. You can, however, link to the survey through the Podcasts app on your Apple and other smart devices, as well as through Spotify, Stitcher and other podcast directory apps and on your computer browser at these websites. We apologize for the inconvenience.)  The information provided through this and all Ridgeview podcasts as well as any and all accompanying files, images, videos and documents is/are for CME/CE and other institutional learning and communication purposes only and is/are not meant to substitute for the independent medical judgment of a physician, healthcare provider or other healthcare personnel relative to diagnostic and treatment options of a specific patient's medical condition.”   FACULTY DISCLOSURE ANNOUNCEMENT  It is our intent that any potential conflict should be identified openly so that the listeners may form their own judgments about the presentation with the full disclosure of the facts. It is not assumed any potential conflicts will have an adverse impact on these presentations. It remains for the audience to determine whether the speaker’s outside interest may reflect a possible bias, either the exposition or the conclusions presented. Planning committee members and presenter(s) have disclosed they have no significant financial relationship with a pharmaceutical company and have disclosed that no conflict of interest exists with the presentation/educational event. SHOW NOTES: Nephrons are the functional unit of the kidneys. The nephrons have specialized capillary beds that have low partial pressures of oxygen which make kidneys susceptible to AKI. The afferent/efferent capillary bed have a unique ability to constrict and dilate to maintain GFR during times of physiologic stress, this is called autoregulation. The thickness of the renal cortex (or essentially where all the glomeruli are located) is important for detecting or estimating the chronicity of kidney disease. A thick cortex tells us that you have decreased renal function. The proximal tubule is the workhorse of the nephron where the electrolytes, proteins and glucose are reabsorbed. Podocytes are specialized epithelial cells that surround the capillary within the glomeruli assisting with the filtration system of the kidney. A strong electronegative charge. A classic disruption of this system leads to nephritic syndrome. The kidney gets about 20% of blood flow from the heart. Prostaglandins and Angiotensin 2 maintain GFR by driving constriction and dilation of the afferent and efferent capillary beds. NSAIDS (diminish the ability to generate prostaglandins through arachidonic acid pathway), ARBs and ACE inhibitors inhibit -- Angiotensin 2 which generates constriction on the afferent and efferent cap beds (preferential on efferent). Patients susceptible to AKI generally have preexisting chronic kidney disease. We detect AKI through creatinine and urine output. Factors that affect creatinine function include: age, gender, lean muscle mass, drugs (bacterium, cimetidine, tyrosine kinase inhibitors), ethnicity, diet. NGAL, KIM-1 and IL-18 are true markers of structural injury to the kidney. They can be found in the serum as well as urine. NGAL and KIM-1 tend to go up rather fast with AKI in comparison to say creatinine.  NGAL (neutrophil gelatinase-associated lipocalin) is one of the earliest and most robustly induced proteins in the kidney after ischemic or nephrotoxic AKI in animal models and KIM-1 (kidney injury molecule-1) is a type 1 transmembrane protein, with immunoglobulin and mucin domain, whose expression is markedly up-regulated in the proximal tubule in the post-ischemic rat kidney. Pre-renal causes of CHF, hypovolemia, V/D, MI, PE, antihypertensives, anaphylaxis, cirrhosis, sepsis, hemorrhage, etc. Essentially: "The kidneys are not getting enough blood flow". Post-renal causes include: obstruction can occur anywhere from renal tubule to the urethra. Generally, bilateral etiology to cause AKI. 1st step in evaluation for AKI is comparing present creatinine with previous and how rapidly the creatinine is rising. Next, how is the patient feeling? Med review, screen of oral intake, loss, infection, etc. Recent procedures. Labs to consider: UA, CBC, US, protein/CR ratio, CBC for TTP and micro-angiopathy.  Additional testing include: Renal U/S, PTH, and anemia may give clues to the duration of decreased renal function/ Active Urine Sediment - concerning for acute glomerulonephritis, hematuria and proteinuria, hematuria, only 80% is bladder, prostate or urethra disease. Quantify the proteinuria, screening for glomerular disease and its severity. 3g: glomerular disease is present. Hyaline casts (Tamm Horsfall) made in Loop of Henle tell us that there is low flow through the tubules. (Generally a pre-renal issue). Granular cast or muddy brown cast which is pathognomonic for ATN which is generally the diagnosis. RBC cast is generally concerning for acute glomerulonephritis may want to consider a nephron consult. Renal U/S is generally recommended for every new AKI. This evaluate for size, hydronephrosis, 2 kidneys, cortical thickness. Management of AKI is managing electrolytes and acidosis. Volume expansion. Trial of vasopressors, dialysis. No benefit to diuretics. Adjusting appropriate drug dosages for patient with AKI. Furosemide stress test can be implemented as diagnostic test to determine the severity of the AKI in volume resus oliguria patient. AKI in the hospital are likely something we did iatrogenic meds, CT contrast, hemodynamics, obstruction, sepsis, volume depletion. Acute Interstitial Nephritis:  Triad of rash, AKI and peripheral eosinophilia very rare (

  Episode 278 is an all inclusive guide to kidney anatomy, health, bloodwork, and MORE for physique and performance based athletes! First I dig into some basics on kidney anatomy and function before moving into some considerations for athletes looking to get bloodwork done to track kidney health, and all before ending with practical application on how to maintain kidney health while pushing for your goals! Also, theres a few references I'll provide below for those looking to take things further!   REFERENCES Adelstein RS, Sellers JR. Effects of calcium on vascular smooth muscle contraction. The American journal of cardiology. Jan 30 1987;59(3):4b-10b.   Agre P, King LS, Yasui M, Guggino WB, Ottersen OP, Fujiyoshi Y, . . . Nielsen S. Aquaporin water channels--from atomic structure to clinical medicine. The Journal of physiology. Jul 1 2002;542(Pt 1):3-16.   AHA. American Heart Association. Kidney Damage and High Blood Pressure. Available at: http://www.heart.org/HEARTORG/Conditions/HighBloodPressure/WhyBloodPressureMatters/Kidney-Damage-and-High-Blood-Pressure_UCM_301825_Article.jsp. Last updated 9/11/2014a. Accessed 8/10/2014.     Akinwusi PO, Oluyombo R, Ogunro PS, Adeniji AO, Okunola OO, Ayodele OE. Low dose aspirin therapy and renal function in elderly patients. International journal of general medicine. 2013;6:19-24.   Al-Awqati Q, Barasch J, Goldman L (ed.), SchaferAI (ed.). Goldman's Cecil Medicine, Twenty-Fourth Edition. Chapter 117: Structure and Function of the Kidneys; 716-720. Copyright 2012 Saunders, an imprint of Elsevier, Inc. Available at: www.clinicalkey.com Accessed: 6/9/2014.   Alpern RJ, Sakhaee K. The clinical spectrum of chronic metabolic acidosis: homeostatic mechanisms produce significant morbidity. American journal of kidney diseases : the official journal of the National Kidney Foundation. Feb 1997;29(2):291-302.   Amodu A, Abramowitz MK. Dietary acid, age, and serum bicarbonate levels among adults in the United States. Clinical journal of the American Society of Nephrology : CJASN. Dec 2013;8(12):2034-2042.   Anders HJ, Andersen K, Stecher B. The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease. Kidney international. Jun 2013;83(6):1010-1016.   Babaei-Jadidi R, Karachalias N, Ahmed N, Battah S, and Thornalley PJ. Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine. Diabetes. 2003;52(8):2110–20   Bae EH, Lee J, Ma SK, et al. alpha-Lipoic acid prevents cisplatin-induced acute kidney injury in rats. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association - European Renal Association. 2009;24(9):2692–700   Balakumar P, Bishnoi HK, Mahadevan N. Telmisartan in the management of diabetic nephropathy: a contemporary view. Current diabetes reviews. May 2012;8(3):183-190.   Balakumar P, Rohilla A, Krishan P, Solairaj P, and Thangathirupathi A. The multifaceted therapeutic potential of benfotiamine. Pharmacol. Res. 2010;61(6):482–8   Bankir L, Bouby N, Trinh-Trang-Tan MM, Ahloulay M, Promeneur D. Direct and indirect cost of urea excretion. Kidney international. Jun 1996;49(6):1598-1607.   Barbagallo M, Dominguez LJ, Galioto A, Pineo A, Belvedere M. Oral magnesium supplementation improves vascular function in elderly diabetic patients. Magnesium research : official organ of the International Society for the Development of Research on Magnesium. Sep 2010;23(3):131-137.   Bashir B, Sharma SG, Stein HD, Sirota RA, D'Agati VD. Acute kidney injury secondary to exposure to insecticides used for bedbug (Cimex lectularis) control. American journal of kidney diseases : the official journal of the National Kidney Foundation. Nov 2013;62(5):974-977.   Baynes JW, Dominiczak MH. Medical Biochemistry, Fourth Edition. Chapter 23: Role of Kidneys in Metabolism; 309-319. Copyright 2014, Elsevier Limited. Available at: www.clinicalkey.com. Accessed 6/9/2014.   Bellizzi V. Low-protein diet or nutritional therapy in chronic kidney disease? Blood purification. 2013;36(1):41–6   Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Critical care (London, England). Aug 2004;8(4):R204-212.   Bertelli AAE, Migliori M, Panichi V. Resveratrol, a component of wine and grapes, in the prevention of kidney disease. Ann N Y Acad Sci. 2002;957:230–8   Brodin EE, Braekkan SK, Vik A, Brox J, Hansen JB. Cystatin C is associated with risk of venous thromboembolism in subjects with normal kidney function--the Tromso study. Haematologica. Jul 2012;97(7):1008-1013.   Busch M, Franke S, Ruster C, and Wolf G. Advanced glycation end-products and the kidney. Eur J Clin Invest. 2010;40(8):742–55   Cacciapuoti F. Lowering homocysteine levels may prevent cardiovascular impairments? Possible therapeutic behaviors. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. Dec 2012;23(8):677-679.   Calhoun DA. Hyperaldosteronism as a common cause of resistant hypertension. Annu. Rev. Med. 2013;64:233–47   Ceglia L, Harris SS, Abrams SA, Rasmussen HM, Dallal GE, Dawson-Hughes B. Potassium bicarbonate attenuates the urinary nitrogen excretion that accompanies an increase in dietary protein and may promote calcium absorption. The Journal of clinical endocrinology and metabolism. Feb 2009;94(2):645-653.   Chao MC, Hu SL, Hsu HS, Davidson LE, Lin CH, Li CI, . . . Lin WY. Serum homocysteine level is positively associated with chronic kidney disease in a Taiwan Chinese population. Journal of nephrology. Jan 16 2014.   Chaudhary DP, Sharma R, Bansal DD. Implications of magnesium deficiency in type 2 diabetes: a review. Biological trace element research. May 2010;134(2):119-129.   Chen J, Muntner P, Hamm LL, et al. The Metabolic Syndrome and Chronic Kidney Disease in U.S. Adults. Ann Intern Med. 2004;140(3):167–74   Chen Y, Abbate M, Tang L. L-Carnitine supplementation for adults with end-stage kidney disease requiring maintenance hemodialysis: a systematic review and meta-analysis. American Journal of Clinical Nutrition. 2014;99(2):408–22   Cheungpasitporn W, Thongprayoon C, OA OC, Edmonds PJ, Kittanamongkolchai W, Erickson SB. Associations of Sugar and Artificially Sweetened Soda and Chronic Kidney Disease: A Systematic Review and Meta-analysis. Nephrology (Carlton, Vic.). Sep 23 2014.   Chrysohoou C, Panagiotakos DB, Pitsavos C, Skoumas J, Zeimbekis A, Kastorini CM, Stefanadis C. Adherence to the Mediterranean diet is associated with renal function among healthy adults: the ATTICA study. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. May 2010;20(3):176-184.   Cohen D, Goldberg M, Gulati A, and Ferri FF. First Consult. Chronic kidney disease. Available at: www.clinicalkey.com. Last updated 5/5/2010. Accessed 6/12/2014. 2010; Available at: [Accessed August 3, 2014].   Cravedi P, Remuzzi G. Pathophysiology of proteinuria and its value as an outcome measure in chronic kidney disease. Br J Clin Pharmacol. 2013;76(4):516–23   Cunningham J, Rodríguez M, Messa P. Magnesium in chronic kidney disease Stages 3 and 4 and in dialysis patients. Clinical Kidney Journal. 2012;5(Suppl 1):i39-i51.   Curiel RV, Katz JD. Mitigating the cardiovascular and renal effects of NSAIDs. Pain Med. 2013;14 Suppl 1:S23–8   Das J, Roy A, Sil PC. Mechanism of the protective action of taurine in toxin and drug induced organ pathophysiology and diabetic complications: a review. Food Funct. 2012;3(12):1251–64     Davis KE, Prasad C, Vijayagopal P, Juma S, Imrhan V. Advanced Glycation End Products, Inflammation, and Chronic Metabolic Diseases:Links in a Chain? Critical reviews in food science and nutrition. Sep 26 2014.   De la Fuente M, Hernanz A, Viniegra S, Miquel J. Sulfur-containing antioxidants increase in vitro several functions of lymphocytes from mice. International immunopharmacology. Jun 2011;11(6):661-669.   Debreceni B, Debreceni L. The role of homocysteine-lowering B-vitamins in the primary prevention of cardiovascular disease. Cardiovascular therapeutics. Jun 2014;32(3):130-138.   Dempsher J. The nerve impulse in the axon--a new theory. Acta biotheoretica. 1981;30(2):121-137.   Di Vito R, Sirolli V, Amoroso L, Bonomini M. [Nephrotoxicity induced by chemotherapy]. Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia. May-Jun 2011;28(3):296-304.   Dong JY, Xun P, He K, Qin LQ. Magnesium intake and risk of type 2 diabetes: meta-analysis of prospective cohort studies. Diabetes care. Sep 2011;34(9):2116-2122.   Downie WW. Prostaglandins and NSAID in the kidney. The Journal of rheumatology. Supplement. Mar 1991;28:19-21.   Duranton F, Cohen G, De Smet R, Rodriguez M, Jankowski J, Vanholder R, Argiles A. Normal and pathologic concentrations of uremic toxins. Journal of the American Society of Nephrology : JASN. Jul 2012;23(7):1258-1270.   Eknoyan G. Obesity and chronic kidney disease. Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia. 2011;31(4):397-403.   Eknoyan G, Latos DL, Lindberg J, National Kidney Foundation Carnitine Consensus Conference. Practice recommendations for the use of L-carnitine in dialysis-related carnitine disorder. National Kidney Foundation Carnitine Consensus Conference. Am J Kidney Dis. 2003;41(4):868–76.     Faloon W. FDA Approves Deadly Drugs, Delays Lifesaving Therapies. Life Extension Magazine. http://www.lef.org//Magazine/2004/5/awsi/Page-01. May 2004. Accessed 1/26/2015.   Feng B, Yan X-F, Xue J-L, Xu L, and Wang H. The Protective Effects of α-Lipoic Acid on Kidneys in Type 2 Diabetic Goto-Kakisaki Rats via Reducing Oxidative Stress. Int J Mol Sci. 2013;14(4):6746–56   Fenton TR, Tough SC, Lyon AW, Eliasziw M, Hanley DA. Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill's epidemiologic criteria for causality. Nutrition journal. 2011;10:41.   Ferri FF. Ferri's Clinical Advisor. Chronic Kidney Disease. Available at: www.clinicalkey.com. Copyright © 2014c. Accessed 6/12/2014.   Ferri FF. Ferri's Clinical Advisor. Acute Kidney Injury. Available at: www.clinicalkey.com. Copyright © 2014a. Accessed 6/12/2014.   Ferri FF. Ferri's Clinical Advisor. Polycystic Kidney Disease. Available at: www.clinicalkey.com. Copyright © 2014b. Accessed 6/12/2014.   Finkielstein VA, Goldfarb DS. Strategies for preventing calcium oxalate stones. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. May 9 2006;174(10):1407-1409.   Fjellstedt E, Denneberg T, Jeppsson JO, Tiselius HG. A comparison of the effects of potassium citrate and sodium bicarbonate in the alkalinization of urine in homozygous cystinuria. Urological research. Oct 2001;29(5):295-302.   Fliser D, Ritz E. Serum cystatin C concentration as a marker of renal dysfunction in the elderly. American journal of kidney diseases : the official journal of the National Kidney Foundation. Jan 2001;37(1):79-83.   Forbes JM, Cooper ME, Oldfield MD, Thomas MC. Role of advanced glycation end products in diabetic nephropathy. Journal of the American Society of Nephrology : JASN. Aug 2003;14(8 Suppl 3):S254-258.     Fung TT, Chiuve SE, McCullough ML, Rexrode KM, Logroscino G, Hu FB. Adherence to a DASH-style diet and risk of coronary heart disease and stroke in women. Archives of internal medicine. Apr 14 2008;168(7):713-720.   Gaedeke J, Fels LM, Bokemeyer C, Mengs U, Stolte H, Lentzen H. Cisplatin nephrotoxicity and protection by silibinin. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. Jan 1996;11(1):55-62.   Gazdíková K, Gvozdjáková A, Kucharská J, Spustová V, Braunová Z, and Dzúrik R. Oxidative stress and plasma concentrations of coenzyme Q10, alpha-tocopherol, and beta-carotene in patients with a mild to moderate decrease of kidney function. Nephron. 2001;88(3):285   Geleijnse JM, Giltay EJ, Grobbee DE, Donders ART, and Kok FJ. Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials. J. Hypertens. 2002;20(8):1493–9   Genazzani AR, Mannella P, Simoncini T. Drospirenone and its antialdosterone properties. Climacteric : the journal of the International Menopause Society. Feb 2007;10 Suppl 1:11-18.   GHR. Genetics Home Reference. Conditions page. Renal tubular dysgenesis. Available at: http://ghr.nlm.nih.gov/condition/renal-tubular-dysgenesis. 1/5/2015. Accessed 1/6/2015. 2015.     Goraya N, Simoni J, Jo C, Wesson DE. Dietary acid reduction with fruits and vegetables or bicarbonate attenuates kidney injury in patients with a moderately reduced glomerular filtration rate due to hypertensive nephropathy. Kidney international. Jan 2012;81(1):86-93.   Goraya N, Wesson DE. Dietary management of chronic kidney disease: protein restriction and beyond. Current opinion in nephrology and hypertension. Nov 2012;21(6):635-640.   Goraya N, Wesson DE. Does correction of metabolic acidosis slow chronic kidney disease progression? Current opinion in nephrology and hypertension. Mar 2013;22(2):193-197.   Gowda S, Desai PB, Kulkarni SS, Hull VV, Math AA, Vernekar SN. Markers of renal function tests. North American journal of medical sciences. Apr 2010;2(4):170-173.   Guarnieri G, Zanetti M, Vinci P, Cattin MR, Pirulli A, Barazzoni R. Metabolic syndrome and chronic kidney disease. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. Sep 2010;20(5 Suppl):S19-23.   Gupta A, Biyani M, and Khaira A. Vancomycin nephrotoxicity: myths and facts. Neth J Med. 2011;69(9):379–83   Hall ME, do Carmo JM, da Silva AA, Juncos LA, Wang Z, Hall JE. Obesity, hypertension, and chronic kidney disease. International journal of nephrology and renovascular disease. 2014;7:75-88.   Hamilton KL, Butt AG. The molecular basis of renal tubular transport disorders. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology. Jul 2000;126(3):305-321.   Hamm LL, Simon EE. Roles and mechanisms of urinary buffer excretion. The American journal of physiology. Oct 1987;253(4 Pt 2):F595-605.   Hanly L, Rieder MJ, Huang SH, Vasylyeva TL, Shah RK, Regueira O, Koren G. N-acetylcysteine rescue protocol for nephrotoxicity in children caused by ifosfamide. Journal of population therapeutics and clinical pharmacology = Journal de la therapeutique des populations et de la pharamcologie clinique. 2013;20(2):e132-145.   Harisa GI. Benfotiamine enhances antioxidant defenses and protects against cisplatin-induced DNA damage in nephrotoxic rats. J. Biochem. Mol. Toxicol. 2013;27(8):398–405   Hartweg J, Farmer AJ, Holman RR, and Neil HAW. Meta-analysis of the effects of n-3 polyunsaturated fatty acids on haematological and thrombogenic factors in type 2 diabetes. Diabetologia. 2007;50(2):250–8   Hataya Y, Igarashi S, Yamashita T, and Komatsu Y. Thyroid hormone replacement therapy for primary hypothyroidism leads to significant improvement of renal function in chronic kidney disease patients. Clinical and experimental nephrology. 2013;17(4):525–31   Hawley MA. The Kidney Transplant/Dialysis Association Patient Handbook. Chapter 1: Normal and Abnormal Kidney Function. Available at: http://msl1.mit.edu/ESD10/kidneys/HndbkHTML/ch1.htm. Accessed 1/6/2015. 2015.   Hazard PB, Griffin JP. Calculation of sodium bicarbonate requirement in metabolic acidosis. The American journal of the medical sciences. Jan-Feb 1982;283(1):18-22.   Heidet L, Gubler M-C. The renal lesions of Alport syndrome. J. Am. Soc. Nephrol. 2009;20(6):1210–5   Ho MJ, Bellusci A, Wright JM. Blood pressure lowering efficacy of coenzyme Q10 for primary hypertension. Cochrane Database Syst Rev. 2009;(4):CD007435   Hodgson JM, Watts GF, Playford DA, Burke V, and Croft KD. Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr. 2002;56(11):1137–42   Hojs R, Bevc S, Antolinc B, Gorenjak M, Puklavec L. Serum cystatin C as an endogenous marker of renal function in the elderly. International journal of clinical pharmacology research. 2004;24(2-3):49-54.   Holthoff JH, Wang Z, Seely KA, Gokden N, and Mayeux PR. Resveratrol improves renal microcirculation, protects the tubular epithelium, and prolongs survival in a mouse model of sepsis-induced acute kidney injury. Kidney Int. 2012;81(4):370–8   Houston M. The role of magnesium in hypertension and cardiovascular disease. Journal of clinical hypertension (Greenwich, Conn.). Nov 2011;13(11):843-847.   Kanda E, Ai M, Yoshida M, Kuriyama R, Shiigai T. High serum bicarbonate level within the normal range prevents the progression of chronic kidney disease in elderly chronic kidney disease patients. BMC nephrology. 2013;14:4.   Karachalias N, Babaei-Jadidi R, Rabbani N, and Thornalley PJ. Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes. Diabetologia. 2010;53(7):1506–16   Karalius VP, Shoham DA. Dietary sugar and artificial sweetener intake and chronic kidney disease: a review. Advances in chronic kidney disease. 2013;20(2):157–64   Karimi G, Ramezani M, Tahoonian Z. Cisplatin nephrotoxicity and protection by milk thistle extract in rats. Evidence-based complementary and alternative medicine : eCAM. Sep 2005;2(3):383-386.   Karsai T, Elodi P. Urea cycle enzymes in human liver: ontogenesis and interaction with the synthesis of pyrimidines and polyamines. Molecular and cellular biochemistry. 1982;43(2):105-110.   Kaur J. A comprehensive review on metabolic syndrome. Cardiology research and practice. 2014;2014:943162.   Kaysen GA. Albumin turnover in renal disease. Mineral and electrolyte metabolism. 1998;24(1):55-63.   Khalifeh N, Haider D, Horl WH. Natriuretic peptides in chronic kidney disease and during renal replacement therapy: an update. Journal of investigative medicine : the official publication of the American Federation for Clinical Research. Jan 2009;57(1):33-39.   Khan SA, Priyamvada S, Khan W, Khan S, Farooq N, and Yusufi ANK. Studies on the protective effect of green tea against cisplatin induced nephrotoxicity. Pharmacol. Res. 2009;60(5):382–91   Kihm LP, Müller-Krebs S, Klein J. Benfotiamine protects against peritoneal and kidney damage in peritoneal dialysis. J. Am. Soc. Nephrol. 2011;22(5):914–26   Kurella M, Lo JC, Chertow GM. Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults. Journal of the American Society of Nephrology : JASN. Jul 2005;16(7):2134-2140.   Kurtz TW. Treating the metabolic syndrome: telmisartan as a peroxisome proliferator-activated receptor-gamma activator. Acta diabetologica. Apr 2005;42 Suppl 1:S9-16.   LaCivita C, Funkhouser E, Miller MJ, Ray MN, Saag KG, Kiefe CI, . . . Allison JJ. Patient-reported communications with pharmacy staff at community pharmacies: the Alabama NSAID Patient Safety Study, 2005-2007. Journal of the American Pharmacists Association : JAPhA. Sep-Oct 2009;49(5):e110-117.   Lacour B, Parry C, Drüeke T, et al. Pyridoxal 5'-phosphate deficiency in uremic undialyzed, hemodialyzed, and non-uremic kidney transplant patients. Clin. Chim. Acta. 1983;127(2):205–15   Lahoti TS, Patel D, Thekkemadom V, Beckett R, Ray SD. Doxorubicin-induced in vivo nephrotoxicity involves oxidative stress-mediated multiple pro- and anti-apoptotic signaling pathways. Current neurovascular research. Nov 2012;9(4):282-295.   Lameire N, Kruse V, Rottey S. Nephrotoxicity of anticancer drugs--an underestimated problem? Acta clinica Belgica. 2011;66(5):337–45   Lassus J, Harjola VP. Cystatin C: a step forward in assessing kidney function and cardiovascular risk. Heart Fail Rev. 2012;17(2):251–61   Latchoumycandane C, Nagy LE, McIntyre TM. Chronic ethanol ingestion induces oxidative kidney injury through taurine-inhibitable inflammation. Free radical biology & medicine. Apr 2014;69:403-416.   Launay-Vacher V, Rey JB, Isnard-Bagins C, et al. Prevention of cisplatin nephrotoxicity: state of the art and recommendations from the European Society of Clinical Pharmacy Special Interest Group on Cancer Care. Cancer Chemother Pharmacol. 2008;61(6):903-9.   Laville M, Nazare JA. Diabetes, insulin resistance and sugars. Obesity reviews : an official journal of the International Association for the Study of Obesity. Mar 2009;10 Suppl 1:24-33.   Le Vaillant J, Pellerin L, Brouard J, Eckart P. [Acetaminophen (paracetamol) causing renal failure: report on 3 pediatric cases]. Archives de pediatrie : organe officiel de la Societe francaise de pediatrie. Jun 2013;20(6):650-653.   Lee JT, Peng GS, Chen SY, Hsu CH, Lin CC, Cheng CA, . . . Lin JC. Homocysteine induces cerebral endothelial cell death by activating the acid sphingomyelinase ceramide pathway. Progress in neuro-psychopharmacology & biological psychiatry. Aug 1 2013;45:21-27.   Leslie RD, Cohen RM. Biologic variability in plasma glucose, hemoglobin A1c, and advanced glycation end products associated with diabetes complications. Journal of diabetes science and technology. Jul 2009;3(4):635-643.   Leu J-G, Lin C-Y, Jian J-H, Shih C-Y, and Liang Y-J. Epigallocatechin-3-gallate combined with alpha lipoic acid attenuates high glucose-induced receptor for advanced glycation end products (RAGE) expression in human embryonic kidney cells. An. Acad. Bras. Cienc. 2013;85(2):745–52   Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Annals of internal medicine. Mar 16 1999;130(6):461-470.   Li H, Weatherford ET, Davis DR, Keen HL, Grobe JL, Daugherty A, . . . Sigmund CD. Renal proximal tubule angiotensin AT1A receptors regulate blood pressure. American journal of physiology. Regulatory, integrative and comparative physiology. Oct 2011;301(4):R1067-1077.   Li G, Gao L, Jia J, Gong X, Zang B, and Chen W. α-Lipoic acid prolongs survival and attenuates acute kidney injury in a rat model of sepsis. Clin. Exp. Pharmacol. Physiol. 2014;41(7):459–68   Lin J, Fung TT, Hu FB, Curhan GC. Association of dietary patterns with albuminuria and kidney function decline in older white women: a subgroup analysis from the Nurses' Health Study. American journal of kidney diseases : the official journal of the National Kidney Foundation. Feb 2011;57(2):245-254.   Lin J, Judd S, Le A, et al. Associations of dietary fat with albuminuria and kidney dysfunction. American Journal of Clinical Nutrition. 2010;92(4):897–904   Linden E, Cai W, He JC, Xue C, Li Z, Winston J, . . . Uribarri J. Endothelial dysfunction in patients with chronic kidney disease results from advanced glycation end products (AGE)-mediated inhibition of endothelial nitric oxide synthase through RAGE activation. Clinical journal of the American Society of Nephrology : CJASN. May 2008;3(3):691-698.   Liu H, Peng Y, Li J, Liu Y, Cheng M, Yuan F, Liu F. [Stages of 3,547 patients with chronic kidney disease and relevant factor analysis]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences. May 2010;35(5):499-510.   Lyman JL. Blood urea nitrogen and creatinine. Emergency medicine clinics of North America. May 1986;4(2):223-233.   Machado V, Cabral A, Monteiro P, et al. Carvedilol as a protector against the cardiotoxicity induced by anthracyclines (doxorubicin). Rev Port Cardiol. 2008;27(10):1277-96.   Magill SB. Pathophysiology, diagnosis, and treatment of mineralocorticoid disorders. Comprehensive Physiology. Jul 2014;4(3):1083-1119.   Malarkodi KP, Balachandar AV, Sivaprasad R, and Varalakshmi P. Prophylactic effect of lipoic acid against adriamycin-induced peroxidative damages in rat kidney. Ren Fail. 2003;25(3):367–77   Mandayam S, Mitch WE. Dietary protein restriction benefits patients with chronic kidney disease. Nephrology (Carlton, Vic.). Feb 2006;11(1):53-57.   Mariani LH, White MT, Shults J, et al. Increasing use of vitamin D supplementation in the chronic renal insufficiency cohort study. Journal of renal nutrition: the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2014;24(3):186–93   Marnett LJ, Rowlinson SW, Goodwin DC, Kalgutkar AS, Lanzo CA. Arachidonic Acid Oxygenation by COX-1 and COX-2: MECHANISMS OF CATALYSIS AND INHIBITION. Journal of Biological Chemistry. August 13, 1999 1999;274(33):22903-22906.   Marre M, Garcia Puig J, Kokot F, Fernandez M, Jermendy G, Opie L, . . . Asmar R. Effect of indapamide SR on microalbuminuria--the NESTOR study (Natrilix SR versus Enalapril Study in Type 2 diabetic hypertensives with micrOalbuminuRia)--rationale and protocol for the main trial. Journal of hypertension. Supplement : official journal of the International Society of Hypertension. Mar 2003;21(1):S19-24.   McCarron DA. Dietary sodium and cardiovascular and renal disease risk factors: dark horse or phantom entry? Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. Jul 2008;23(7):2133-2137.   MedicineNet. Metabolic Syndrome: How is metabolic syndrome defined? Available at: http://www.medicinenet.com/metabolic_syndrome/article.htm#how_is_metabolic_syndrome_defined. 9/19/2014. Accessed 9/19/2014.   Mehdi U, Toto RD. Anemia, diabetes, and chronic kidney disease. Diabetes care. Jul 2009;32(7):1320-1326.   Mekki K, Bouzidi-bekada N, Kaddous A, Bouchenak M. Mediterranean diet improves dyslipidemia and biomarkers in chronic renal failure patients. Food & function. Oct 2010;1(1):110-115.   Menon V, Shlipak MG, Wang X, Coresh J, Greene T, Stevens L, . . . Sarnak MJ. Cystatin C as a risk factor for outcomes in chronic kidney disease. Annals of internal medicine. Jul 3 2007;147(1):19-27.   Meola M, Petrucci I. [Ultrasound and color Doppler in nephrology. Acute kidney injury]. Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia. Sep-Oct 2012;29(5):599-615.   Meyer BR. Renal function in aging. Journal of the American Geriatrics Society. Aug 1989;37(8):791-800.   Michael A, Faga T, Pisani A, and Riccio E. Molecular mechanisms of renal cellular nephrotoxicity due to radiocontrast media. 2014;2014:249810   Minich DM, Bland JS. Acid-alkaline balance: role in chronic disease and detoxification. Alternative therapies in health and medicine. Jul-Aug 2007;13(4):62-65.   Mirmiran P, Shab-Bidar S, Hosseini-Esfahani F, Asghari G, Hosseinpour-Niazi S, Azizi F. Magnesium intake and prevalence of metabolic syndrome in adults: Tehran Lipid and Glucose Study. Public health nutrition. Apr 2012;15(4):693-701.   Mithieux G, Andreelli F, Magnan C. Intestinal gluconeogenesis: key signal of central control of energy and glucose homeostasis. Current opinion in clinical nutrition and metabolic care. Jul 2009;12(4):419-423.   Mithieux G, Misery P, Magnan C, Pillot B, Gautier-Stein A, Bernard C, . . . Zitoun C. Portal sensing of intestinal gluconeogenesis is a mechanistic link in the diminution of food intake induced by diet protein. Cell Metab. Nov 2005;2(5):321-329.   Mithieux G. A novel function of intestinal gluconeogenesis: central signaling in glucose and energy homeostasis. Nutrition (Burbank, Los Angeles County, Calif.). Sep 2009;25(9):881-884.   Moe SM, Saifullah A, LaClair RE, Usman SA, Yu Z. A randomized trial of cholecalciferol versus doxercalciferol for lowering parathyroid hormone in chronic kidney disease. Clinical journal of the American Society of Nephrology : CJASN. Feb 2010;5(2):299-306.   Molnar MZ, Kalantar-Zadeh K, Lott EH, Lu JL, Malakauskas SM, Ma JZ, . . . Kovesdy CP. Angiotensin-converting enzyme inhibitor, angiotensin receptor blocker use, and mortality in patients with chronic kidney disease. Journal of the American College of Cardiology. Feb 25 2014;63(7):650-658.   Montemurno E, Cosola C, Dalfino G, Daidone G, De Angelis M, Gobbetti M, Gesualdo L. What Would You Like to Eat, Mr CKD Microbiota? A Mediterranean Diet, please! Kidney & blood pressure research. Jul 29 2014;39(2-3):114-123.   Mori TA, Burke V, Puddey I, et al. The effects of [omega]3 fatty acids and coenzyme Q10 on blood pressure and heart rate in chronic kidney disease: a randomized controlled trial. J. Hypertens. 2009;27(9):1863–72   Mountokalakis TD. Magnesium metabolism in chronic renal failure. Magnesium research : official organ of the International Society for the Development of Research on Magnesium. Jun 1990;3(2):121-127.   Munekage E, Takezaki Y, Hanazaki K. [Shortage and metabolic disturbance of magnesium in diabetic patients and significance of magnesium replacement therapy]. Clinical calcium. Aug 2012;22(8):1235-1242.   Murray MD, Brater DC. Renal toxicity of the nonsteroidal anti-inflammatory drugs. Annual review of pharmacology and toxicology. 1993;33:435-465.   Mussap M, Dalla Vestra M, Fioretto P, Saller A, Varagnolo M, Nosadini R, Plebani M. Cystatin C is a more sensitive marker than creatinine for the estimation of GFR in type 2 diabetic patients. Kidney international. Apr 2002;61(4):1453-1461.   Nakamura T, Fujiwara N, Kawagoe Y, Sugaya T, Ueda Y, Koide H. Effects of telmisartan and enalapril on renoprotection in patients with mild to moderate chronic kidney disease. European journal of clinical investigation. Sep 2010;40(9):790-796.   Nakamura S, Li H, Adijiang A, Pischetsrieder M, and Niwa T. Pyridoxal phosphate prevents progression of diabetic nephropathy. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association - European Renal Association. 2007;22(8):2165–74   Nashar K, Egan BM. Relationship between chronic kidney disease and metabolic syndrome: current perspectives. Diabetes, metabolic syndrome and obesity : targets and therapy. 2014;7:421-435.   Navar LG. The kidney in blood pressure regulation and development of hypertension. The Medical clinics of North America. Sep 1997;81(5):1165-1198.   Nderitu P, Doos L, Jones PW, Davies SJ, Kadam UT. Non-steroidal anti-inflammatory drugs and chronic kidney disease progression: a systematic review. Family practice. Jun 2013;30(3):247-255.   Newman DJ, Thakkar H, Edwards RG, Wilkie M, White T, Grubb AO, Price CP. Serum cystatin C measured by automated immunoassay: a more sensitive marker of changes in GFR than serum creatinine. Kidney international. Jan 1995;47(1):312-318.   NHGRI. National Human Genome Research Institute. Health page. Learning About Autosomal Dominant Polycystic Kidney Disease. Last updated 4/18/2013. Accessed 1/6/2015.   NIH. National Institutes of Health. MedlinePlus. Kidney Disease: Early Detection and Treatment. Available at: http://www.nlm.nih.gov/medlineplus/magazine/issues/winter08/articles/winter08pg9-10.html. Copyright 2008. Accessed 9/19/2014.   NKDEP. National Kidney Disease Education Program. Laboratory Evaluation page. Reporting GFR. Available at: http://nkdep.nih.gov/lab-evaluation/gfr/reporting.shtml. Last updated 6/6/2012. Accessed 10/21/2014.   NKF. National Kidney Foundation. About Chronic Kidney Disease. Available at: http://www.kidney.org/kidneydisease/aboutckd. Copyright 2013a. Accessed 9/19/2014.   NKF. National Kidney Foundation. Acute Kidney Injury. Available at: http://www.kidney.org/news/kidneyCare/fall10/AcuteKidneyInjury. Copyright 2013b. Accessed 9/19/2014.   NKF. National Kidney Foundation. Statement on the release of ibuprofen as an over-the-counter medicine. Ad Hoc Committee for the National Kidney Foundation. American journal of kidney diseases : the official journal of the National Kidney Foundation. Jul 1985;6(1):4-6.     Patrick L. Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Altern Med Rev. 2002;7(6):456–71   Penno G, Solini A, Bonora E, Fondelli C, Orsi E, Zerbini G, . . . Pugliese G. HbA1c variability as an independent correlate of nephropathy, but not retinopathy, in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicenter study. Diabetes care. Aug 2013;36(8):2301-2310.   Perneger TV, Whelton PK, Klag MJ. Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs. The New England journal of medicine. Dec 22 1994;331(25):1675-1679.   Post-White J, Ladas EJ, Kelly KM. Advances in the use of milk thistle (Silybum marianum). Integrative cancer therapies. Jun 2007;6(2):104-109.   Pozzi C, Marai P, Ponti R, Dell'Oro C, Sala C, Zedda S, Locatelli F. Toxicity in man due to stain removers containing 1,2-dichloropropane. British journal of industrial medicine. Nov 1985;42(11):770-772.   Prieto J, Qian C, Garcia N, Diez J, Medina JF. Abnormal expression of anion exchanger genes in primary biliary cirrhosis. Gastroenterology. Aug 1993;105(2):572-578.   PubMed Health. DASH Eating Plan. Available at: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0063068/. Last updated 6/11/2014. Accessed 10/21/2014.   Pushpakumar SB, Kundu S, Sen U. Endothelial dysfunction: The link between homocysteine and hydrogen sulfide. Current medicinal chemistry. Jul 6 2014.   Qin J, Wang H, Rets A, Harari S, Alexis H, Eid I, Pincus MR. Stability of BUN and creatinine determinations on the Siemens Advia 1800 analyzer. Journal of clinical laboratory analysis. Nov 2013;27(6):435-437.   Quigley R. Chronic kidney disease: highlights for the general pediatrician. International journal of pediatrics. 2012;2012:943904.   Radbill B, Murphy B, LeRoith D. Rationale and strategies for early detection and management of diabetic kidney disease. Mayo Clinic proceedings. Dec 2008;83(12):1373-1381.     Sabolić I. Common mechanisms in nephropathy induced by toxic metals. Nephron Physiol. 2006;104(3):p107–14   Saddadi F, Alatab S, Pasha F, Ganji MR, Soleimanian T. The effect of treatment with N-acetylcysteine on the serum levels of C-reactive protein and interleukin-6 in patients on hemodialysis. Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia. Jan 2014;25(1):66-72.   Sahin K, Tuzcu M, Gencoglu H, et al. Epigallocatechin-3-gallate activates Nrf2/HO-1 signaling pathway in cisplatin-induced nephrotoxicity in rats. Life Sci. 2010;87(7-8):240–5   Saifan C, Samarneh M, Shtaynberg N, Nasr R, El-Charabaty E, and El-Sayegh S. Treatment of confirmed B12 deficiency in hemodialysis patients improves Epogen® requirements. Int J Nephrol Renovasc Dis. 2013;6:89–93   Saldanha JF, Leal Vde O, Stenvinkel P, Carraro-Eduardo JC, and Mafra D. Resveratrol: why is it a promising therapy for chronic kidney disease patients? Oxid Med Cell Longev. 2013;2013:963217   Salerno MP, Piselli P, Rossi E, Favi E, Gargiulo A, Spagnoletti G, . . . Citterio F. Metabolic syndrome and cardiovascular disease in kidney transplantation. Transplantation proceedings. May 2011;43(4):1067-1068.   Salgado JV, Souza FL, Salgado BJ. How to understand the association between cystatin C levels and cardiovascular disease: Imbalance, counterbalance, or consequence? Journal of cardiology. Dec 2013;62(6):331-335.   Samuni Y, Goldstein S, Dean OM, and Berk M. The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta. 2013;1830(8):4117–29   Scialla JJ, Appel LJ, Astor BC, Miller ER, 3rd, Beddhu S, Woodward M, . . . Anderson CA. Estimated net endogenous acid production and serum bicarbonate in African Americans with chronic kidney disease. Clinical journal of the American Society of Nephrology : CJASN. Jul 2011;6(7):1526-1532.   Segal R, Lubart E, Leibovitz A, Iaina A, Caspi D. Renal effects of low dose aspirin in elderly patients. The Israel Medical Association journal : IMAJ. Oct 2006;8(10):679-682.   Seifter JL. Acid-base disorders. Chapter 120. Pages 741-753. In: Goldman’s Cecil Medicine. Published 12/31/2011. Available at: www.clinicalkey.com. Accessed 10/21/2014.   Sener G, Sehirli O, Ipci Y, Cetinel S, Cikler E, Gedik N, Alican I. Protective effects of taurine against nicotine-induced oxidative damage of rat urinary bladder and kidney. Pharmacology. Apr 2005;74(1):37-44.   Senturk H, Kabay S, Bayramoglu G, et al. Silymarin attenuates the renal ischemia/reperfusion injury-induced morphological changes in the rat kidney. World J Urol. 2008;26(4):401–7   Shepler B, Nash C, Smith C, Dimarco A, Petty J, and Szewciw S. Update on potential drugs for the treatment of diabetic kidney disease. Clin Ther. 2012;34(6):1237–46   Shin BC, Kwon YE, Chung JH, and Kim HL. The antiproteinuric effects of green tea extract on acute cyclosporine-induced nephrotoxicity in rats. Transplant. Proc. 2012;44(4):1080–2   Shin DH, Lee MJ, Kim SJ, et al. Preservation of renal function by thyroid hormone replacement therapy in chronic kidney disease patients with subclinical hypothyroidism. J Clin Endocrinol Metab. 2012;97(8):2732–40   Shishehbor MH, Oliveira LP, Lauer MS, Sprecher DL, Wolski K, Cho L, . . . Hazen SL. Emerging cardiovascular risk factors that account for a significant portion of attributable mortality risk in chronic kidney disease. The American journal of cardiology. Jun 15 2008;101(12):1741-1746.   Shlipak MG, Matsushita K, Arnlov J, Inker LA, Katz R, Polkinghorne KR, . . . Gansevoort RT. Cystatin C versus creatinine in determining risk based on kidney function. The New England journal of medicine. Sep 5 2013;369(10):932-943.   Shlipak MG, Mattes MD, Peralta CA. Update on cystatin C: incorporation into clinical practice. American journal of kidney diseases : the official journal of the National Kidney Foundation. Sep 2013;62(3):595-603.   Soto C, Pérez J, García V, Uría E, Vadillo M, and Raya L. Effect of silymarin on kidneys of rats suffering from alloxan-induced diabetes mellitus. Phytomedicine. 2010;17(14):1090–4   Soulage CO, Koppe L, Fouque D. Protein-bound uremic toxins...new targets to prevent insulin resistance and dysmetabolism in patients with chronic kidney disease. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. Nov 2013;23(6):464-466.   Stanton RC. Clinical challenges in diagnosis and management of diabetic kidney disease. American journal of kidney diseases : the official journal of the National Kidney Foundation. Feb 2014;63(2 Suppl 2):S3-21.   Starke A, Corsenca A, Kohler T, Knubben J, Kraenzlin M, Uebelhart D, . . . Ambuhl PM. Correction of metabolic acidosis with potassium citrate in renal transplant patients and its effect on bone quality. Clinical journal of the American Society of Nephrology : CJASN. Sep 2012;7(9):1461-1472.   Szczepańska-Konkel M, Dominiczak MH, JW B. Medical Biochemistry, Fourth Edition. Chapter 23: Role of Kidneys in Metabolism; 309-319. Copyright 2014, Elsevier Limited. Available at: www.clinicalkey.com Accessed 6/9/2014.   Tang PC, Ng YF, Ho S, Gyda M, Chan SW. Resveratrol and cardiovascular health - Promising therapeutic or hopeless illusion? Pharmacological research : the official journal of the Italian Pharmacological Society. Dec 2014;90c:88-115.   Tanner GA, Tanner JA. Citrate therapy for polycystic kidney disease in rats. Kidney international. Nov 2000;58(5):1859-1869.   Wackenfors A, Pantev E, Emilson M, Edvinsson L, Malmsjo M. Angiotensin II receptor mRNA expression and vasoconstriction in human coronary arteries: effects of heart failure and age. Basic & clinical pharmacology & toxicology. Dec 2004;95(6):266-272.   Wagner E. Life Extension Magazine; In The News. Cystatin C Valuable in Detecting Kidney Dysfunction. http://www.lef.org//Magazine/2006/12/itn/Page-01. 2006. Accessed 1/27/2015.   Watanabe H, Obata H, Watanabe T, Sasaki S, Nagai K, Aizawa Y. Metabolic syndrome and risk of development of chronic kidney disease: the Niigata preventive medicine study. Diabetes/metabolism research and reviews. Jan 2010;26(1):26-32.   Yadla M, Yanala SR, Parvithina S, Chennu KK, Annapindi N, Vishnubhotla S. Acute kidney injury in endosulfan poisoning. Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia. May 2013;24(3):592-593.   Yamagishi S, Nakamura K, Matsui T. Potential utility of telmisartan, an angiotensin II type 1 receptor blocker with peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-modulating activity for the treatment of cardiometabolic disorders. Current molecular medicine. Aug 2007;7(5):463-469.   Yao X, Panichpisal K, Kurtzman N, et al. Cisplatin nephrotoxicity: a review. Am J Med Sci. 2007;334(2):115-24.   Yokozawa T, Nakagawa T, Oya T, Okubo T, and Juneja LR. Green tea polyphenols and dietary fibre protect against kidney damage in rats with diabetic nephropathy. J. Pharm. Pharmacol. 2005;57(6):773–80   Younes N, Cleary PA, Steffes MW, de Boer IH, Molitch ME, Rutledge BN, . . . Dahms W. Comparison of urinary albumin-creatinine ratio and albumin excretion rate in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Clinical journal of the American Society of Nephrology : CJASN. Jul 2010;5(7):1235-1242.   Yuzbashian E, Asghari G, Mirmiran P, Hosseini FS, Azizi F. Associations of dietary macronutrients with glomerular filtration rate and kidney dysfunction: Tehran lipid and glucose study. Journal of nephrology. Jun 5 2014.   Zheng Z, Shi H, Jia J, Li D, Lin S. Vitamin D supplementation and mortality risk in chronic kidney disease: a meta-analysis of 20 observational studies. BMC nephrology. 2013;14:199.   Zhu JR, Bai J, Cai NS, Tang B, Fan WH, Guo JZ, . . . Cheng NN. Efficacy and safety of telmisartan vs. losartan in control of mild-to-moderate hypertension: a multicentre, randomised, double-blind study. International journal of clinical practice. Supplement. Dec 2004(145):46-49.   Zoccali C, Curatola G, Panuccio V, Tripepi R, Pizzini P, Versace M, . . . Mallamaci F. Paricalcitol and endothelial function in chronic kidney disease trial. Hypertension. 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Commentary by Dr. Valentin Fuster

Dr. J. Brian Byrd is an assistant professor of internal medicine at the University of Michigan Medical School. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. J.B. Byrd, G.M. Chertow, and V. Bhalla. Hypertension Hot Potato — Anatomy of the Angiotensin-Receptor Blocker Recalls. N Engl J Med 2019;380:1589-1591.

In this episode I cover the pathophysiology, causes, investigations and management of hyperaldosteronism.If you want to follow along with written notes on hyperaldosteronism go to zerotofinals.com/hyperaldosteronism or find the endocrinology section in the Zero to Finals medicine book.This episode covers the pathophysiology, causes, investigations and management of hyperaldosteronism. We specifically look at the renin-angiotensin-aldosterone system, renal artery stenosis and aldosterone antagonists. 

Asst Prof Ashish Khanna (Cleveland, USA) discusses the ATHOS-3 trial, investigating angiotensin II in vasodilatory shock at the Critical Care Reviews Meeting 2018 in Belfast. Prof Anthony Gordon (London, England) provides a brief editorial afterwards.

On today's episode, I cover the angiotensin receptor blockers. Pharmacology Drug Interactions Adverse effects Clinical Pearls

Commentary by Dr. Valentin Fuster

There are a lot of physicians who still believe that TRT will exacerbate prostate cancer, and that people on TRT can take AIs. What does research actually tell us about this? Why should you consider optimization? What is the relationship between sex hormone binding globulin and testosterone? On this episode, double board certified physician and PhD candidate, Dr. Nick Sakkas goes deep on these questions and provides insights backed by some interesting recent research. Testosterone induces cell apoptosis of prostate cancer and inhibits proliferation. -Dr. Nick Sakkas Three Takeaways You have to understand how SHBG is going to affect the testosterone molecularly before you do TRT. Undergoing TRT and taking an AI suppresses estrogen and puts you at an extreme risk of developing cardiac hypertrophy and organ damage in the long-term. On prostate cancer: low testosterone levels are associated with a poor prognosis.   At the start of the show, Dr. Nick shared how he got started, and we talked about sex hormone binding globulin and why its levels will determine the effectiveness of TRT. Next, we talked about a huge misconception people have about prostate cancer and TRT, and what the research really says about it. We also discussed what so many doctors are getting wrong about estrogen with optimization patients, and how you should really consider AIs. Towards the end, we talked about androgens and calcium retention. We also discussed: Why it’s critical that you do not suppress estrogen How optimization changes everything How often a healthy TRT patient should get their arteries checked Angiotensin blockers   Why Vitamin K2 supplements will save your heart and brain Hormone replacement will change your life in many ways, including inhibiting the proliferation of prostate cancer. When it comes to TRT, it’s not wise to rush into taking an AI. Wait for both your estrogen and testosterone to stabilize, for between 6 months to a year. It’s also necessary to consider your sex hormone binding globulin. It is the center of all hormonal evaluation, and must be considered before undergoing TRT.   Guest Bio Dr. Sakkas is a physician, researcher and PhD candidate in the field of molecular endicronology. To get in touch, find him on Facebook https://www.facebook.com/nikosakk88 or email nikosakkis.gmail.com.

Did you know that our kidneys control our blood pressure? It does this so it can continually create 180 litres of filtered blood every day to keep us healthy! The system that the kidneys use to control blood pressure is called the renin angiotensin aldosterone system (RAAS) - it's a big name but easy to learn! Many patients with hypertension manage their blood pressure by taking medications that act upon this system! Join Dr. Matt & Dr. Mike in this episode to explore this clinically important system! 

Commentary by Dr. Valentin Fuster

This podcast highlights original research published in the December 2016 issue of Otolaryngology–Head and Neck Surgery, the official journal of the American Academy of Otolaryngology—Head and Neck Surgery (AAO-HNS) Foundation. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been shown to suppress expression of periostin, a matricellular protein that is markedly elevated in nasal polyp tissue. The purpose of this study was to determine whether use of these antihypertensive agents affects the time to revision sinus surgery in patients with polyp regrowth.  Use of ACEIs and ARBs is associated with an increased time to revision sinus surgery among patients with concurrent nasal polyps and asthma. A possible mechanism of this observed effect is suppression of periostin expression through inhibition of the angiotensin pathway.   Click here to read the full article.

Commentary by Dr. Valentin Fuster

TRPC-Kanäle 1-7 wurden bisher als unselektive Kationenkanäle in heterologen Expressionssystemen beschrieben. Ihre physiologische und pathophysiologische Rolle in verschiedenen Organen und Geweben des menschlichen Körpers ist aber noch weitgehend unklar. Ziel dieser Arbeit war es, die Funktion zweier Mitglieder der TRPC-Familie, TRPC1 und TRPC6, in verschiedenen Zellsystemen mit Hilfe von Untersuchungen an den entsprechenden gendefizienten Mausmodellen näher zu analysieren. Nach der Klonierung der codierenden Sequenz des murinen TRPC1-Proteins aus Mausgeweben, wurden murine embryonale Fibroblasten (MEFs) aus TRPC1-defizienten und Wildtyp-Mäusen isoliert. Ein Vergleich zeigte, dass das Fehlen des TRPC1-Kanals die Viabilität dieser Zellen signifikant steigerte und die Wundheilungsrate signifikant herabsetzte. Durch die Identifikation sogenannter überaktivierter TRPC6-Kanal-Mutanten in Patienten mit fokaler segmentaler Glomerulosklerose (FSGS) war dann insbesondere die Funktion dieses Kanals in den Podozyten der Niere von besonderem Interesse. Wenig später wurden auch funktionslose Mutanten der Phospholipase C-e (PLCe) in Patienten mit dem gleichen oder einem ähnlichen Krankheitsbild beschrieben, das zu einer Erhöhung des Serumproteingehalts im Urin (Proteinurie) führt. Zur Beantwortung der Frage, ob beide Proteine interagieren und Komponenten eines gemeinsamen Signalweges sind, wurden primäre Podozyten aus Mäusen isoliert. In der Tat wurde in primären Podozyten und in HEK293-Zellen eine Interaktion beider Proteine identifiziert und ein möglicher Signalweg von der Aktivierung des Angiotensin 1-Rezeptors zum PLCe-induzierten Calciumioneneinstrom durch TRPC6-Kanäle aufgezeigt. Darüber hinaus wurden TRPC6-, PLCe- und TRPC6/PLCe-defiziente Podozyten mit Wildtyp-Podozyten in funktionellen Testsystemen verglichen. Zunächst konnte eine vermehrte Expression von TRPC4- und TRPC5-Kanälen in PLCe-defizienten und TRPC6/PLCe-defizienten Podozyten identifiziert werden. Außerdem zeigte sich in ersten Untersuchungen, dass das Fehlen des TRPC6-Kanals zu einer erhöhten Zellviabilität und zu einer verminderten Apoptoserate der Podozyten führte. In sog. Calcium-Imaging-Experimenten wurde ein stark reduzierter Calciumioneneinstrom in TRPC6- und PLCe-defizienten Podozyten nach AT1-Rezeptoraktivierung durch Angiotensin II beobachtet. Da Podozyten durch ihre Barrierefunktion wesentlich zur Stabilität des glomerulären Filters beitragen, wurde auch die Veränderung des Zytoskeletts durch Aktinpolymerisation näher untersucht. Es zeigte sich, dass Podozyten nach Applikation von Angiotensin II durch eine stärkere Polymerisation von globulärem Aktin vermehrt sog. Aktin-Stressfibern ausbilden und abflachen. TRPC6-defiziente Podozyten hingegen zeigen bereits im Ruhezustand deutlich mehr Aktin-Stressfibern, die nach Gabe von Angiotensin II nicht mehr signifikant in ihrer Anzahl zunehmen. Die Daten der vorliegenden Arbeit sind im Einklang mit der Hypothese, dass ein zu starker Calciumioneneinstrom in Podozyten durch überaktivierende TRPC6-Mutationen zu einer geringeren Podozytenstabilität und zu einer erhöhten Apoptoserate führen kann. Die mangelnde Stabilität des glomerulären Filters in den FSGS-Patienten führt dann zu einer Proteinurie und schließlich zum Nierenversagen. Durch Expression der TRPC6-Mutationen in TRPC6-defizienten Podozyten könnte sich in Zukunft die Rolle des Kanals als wichtige pharmakologische Zielsubstanz für eine Pharmakotherapie der FSGS bestätigen.

The angiotensin converting enzyme (ACE) has been repeatedly discussed as susceptibility factor for major depression (MD) and the bi-directional relation between MD and cardiovascular disorders (CVD). In this context, functional polymorphisms of the ACE gene have been linked to depression, to antidepressant treatment response, to ACE serum concentrations, as well as to hypertension, myocardial infarction and CVD risk markers. The mostly investigated ACE Ins/Del polymorphism accounts for ~40%-50% of the ACE serum concentration variance, the remaining half is probably determined by other genetic, environmental or epigenetic factors, but these are poorly understood. The main aim of the present study was the analysis of the DNA methylation pattern in the regulatory region of the ACE gene in peripheral leukocytes of 81 MD patients and 81 healthy controls. We detected intensive DNA methylation within a recently described, functional important region of the ACE gene promoter including hypermethylation in depressed patients (p = 0.008) and a significant inverse correlation between the ACE serum concentration and ACE promoter methylation frequency in the total sample (p = 0.02). Furthermore, a significant inverse correlation between the concentrations of the inflammatory CVD risk markers ICAM-1, E-selectin and P-selectin and the degree of ACE promoter methylation in MD patients could be demonstrated (p = 0.01 - 0.04). The results of the present study suggest that aberrations in ACE promoter DNA methylation may be an underlying cause of MD and probably a common pathogenic factor for the bi-directional relationship between MD and cardiovascular disorders.

For Easter this week, we explore how synchrotron radiation can be used to probe and find answers to a variety of scientific questions as we bring you a special programme of highlights from the Diamond Light Source podcast. We hear how changes to key proteins can cause hypertension and pre-eclampsia, how green rust could provide a greener future and discover a new type of magnetic material which could make data storage faster, cheaper and more compact. Plus, we explore a new form of solar cell which could make solar energy more affordable in the future. Like this podcast? Please help us by supporting the Naked Scientists

For Easter this week, we explore how synchrotron radiation can be used to probe and find answers to a variety of scientific questions as we bring you a special programme of highlights from the Diamond Light Source podcast. We hear how changes to key proteins can cause hypertension and pre-eclampsia, how green rust could provide a greener future and discover a new type of magnetic material which could make data storage faster, cheaper and more compact. Plus, we explore a new form of solar cell which could make solar energy more affordable in the future. Like this podcast? Please help us by supporting the Naked Scientists

This month we probe down into the world of structural biology to find out just what this field is and the molecules it can enable us to see. We discover how visualising molecules such as DNA and proteins can help us understand the development of our nervous system, the repair of our DNA and find better treatments for conditions like hypertension and pre-eclampsia, as well as bring you the latest news and developments from Diamond. Like this podcast? Please help us by supporting the Naked Scientists

This month we probe down into the world of structural biology to find out just what this field is and the molecules it can enable us to see. We discover how visualising molecules such as DNA and proteins can help us understand the development of our nervous system, the repair of our DNA and find better treatments for conditions like hypertension and pre-eclampsia, as well as bring you the latest news and developments from Diamond. Like this podcast? Please help us by supporting the Naked Scientists

This month we probe down into the world of structural biology to find out just what this field is and the molecules it can enable us to see. We discover how visualising molecules such as DNA and proteins can help us understand the development of our nervous system, the repair of our DNA and find better treatments for conditions like hypertension and pre-eclampsia, as well as bring you the latest news and developments from Diamond.

Jennifer from the SMJ talks to Dr. William Frishman about the use of angiotensin receptor blockers in the treatment of uncomplicated hypertension.

Mechanical stimulation of the angiotensin receptor promotes cell survival by preferentially activating beta-arrestin-dependent signaling.

Here are four science stories, but only three are true. See if you know which story is TOTALLY BOGUS.

Fri, 17 Jul 2009 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/10390/

Alan Daugherty, PhD, DSc, discusses the influence of Angiotensin in the induction of Abdominal Aortic Aneurism Disease in mice. (September 4, 2008)

Audio Journal of Cardiovascular Medicine Direct Renin Inhibitor Combined with Angiotensin Receptor Blockade Gives Additional Blood Pressure Lowering REFERENCE: Abstract 405-12, American College of Cardiology New Orleans SUZANNE OPARIL, University of Alabama, Birmingham A combination of two antihypertensive agents has given improved blood pressure control in a study with nearly 2000 patients reported to the ACC meeting in New Orleans by a group from the University of Alabama at Birmingham. Suzanne Oparil presented findings on the use of the direct rennin inhibitor, aliskiren, combined with the angiotensin receptor blocker, valsartan. She explained to Peter Goodwin how this “dual renin system blockade” gave enhanced blood pressure lowering in patients with mild to moderate hypertension who were followed with ambulatory monitoring.

Aims: A number of intervention studies have shown that therapy with angiotensin receptor blockers, such as irbesartan, can improve metabolic parameters and reduce the incidence of diabetes mellitus. It is unknown whether this observation also holds true in routine clinical settings. Methods: We evaluated the effect of irbesartan (150 mg or 300 mg/d) together with or without hydrochlorothiazide (12.5 mg/d) in 3259 German patients. A total of 750 primary care physicians evaluated up to 5 subsequent patients with metabolic syndrome (58.9% diabetic), in whom irbesartan therapy was newly initiated (87%) or continued (13%). Results: Six months of irbesartan therapy decreased systolic blood pressure by 14% (157.4 +/- 14.7 vs. 135.0 +/- 10.7 mmHg) and diastolic blood pressure by 13% (92.9 +/- 9.2 vs. 80.8 +/- 6.8 mmHg). This was associated with a decrease in body weight (-2.3%), fasting glucose (-9.5%), HbA1c (-4.6%), LDL-cholesterol (-11%), triglycerides (-16%) and gamma-GT (-12%) and an increase in HDL-cholesterol (+5%). These changes were somewhat more pronounced in male than in female patients and in obese than in lean patients. Changes in glucose concentration and HbA1c were much more prominent in diabetic patients. Conclusion: Irbesartan therapy improves metabolic parameters in routine clinical settings. Thus, our study confirms previously published results from large intervention trials and extends the findings to routine clinical practice.

Background. Experimental studies have shown an activation of the angiotensin-converting enzyme (ACE) system as a response to endothelial injury. Recent publications have elucidated the hypothesis that the ACE gene polymorphism may influence the level of late luminal loss after coronary stent implantation. It is still unclear whether the polymorphism of the angiotensin gene is a major predictor of the extent of neointimal hyperplasia. In this multicenter study, we therefore tested the relationship between the ACE gene polymorphism and the restenosis rate after coronary stent implantation. Methods: As a substudy of the optimization with intracoronary, ultrasound (ICUS) to reduce stent restenosis (OPTICUS) study, we analyzed ACE serum levels and the ACE gene polymorphism in 154 patients at 9 different centers. All patients underwent elective coronary stent implantation in a stenosis of a major coronary vessel. Balloon inflations were repeated until a satisfactory result was achieved in on-line quantitative coronary angiography or ICUS fulfilling the OPTICUS study criteria. After follow-up of 6 months, all patients underwent reangiography tinder identical projections as the baseline procedure. A blinded quantitative analysis of the initial procedure as well as the follow-up examinations were performed by an independent core laboratory. ACE gene polymorphism and ACE serum activity were measured at the 6-month follow-up in a double-blinded setting. Results: With respect to the ACE gene polymorphism, there were three subgroups: DID genotype (48 patients), ID (83 patients) and 11 (23 patients). The subgroups did not differ in regard to age, gender, extent of coronary artery disease, stenosis length, initial degree of stenosis or degree of stenosis after stent implantation. In all, 39 patients (25.3%) had significant restenosis: 12 DD patients (25.0%), 18 ID patients (21.7%) and 9 II patients (39.1%) (odds ratio 2.164, 95% confidence interval 0.853-5.493). We obtained the following results for ACE serum levels: 0.53 mumol/l/s in the DD subgroup, 0.29 mumol/l/s in the ID.

Sun, 1 Jan 1989 12:00:00 +0100 https://epub.ub.uni-muenchen.de/9756/1/9756.pdf Schill, W.-B.; Frick, J.; Fink, Edwin; Niederhauser, H.; Krassnigg, F