Podcasts about adme

In this podcast Simon Taylor (Pharmaron UK) interviews Kevin Beaumont, a highly experienced DMPK scientist, leader and drug developer who has lived and breathed the role of the DMPK Project Representative throughout his 40-year industrial career.  With experience of delivering clinical drug candidates across multiple therapeutic areas with two major pharma companies (Pfizer and AstraZeneca) Kevin describes his entry into the role, the value of people, in roles as mentee and mentor, and the shift in emphasis of DMPK from a discipline supporting drug development to one driving drug discovery.  Covering key concepts related to project DMPK and minimising drug attrition this is a wide-ranging discussion with real life examples spanning discovery to clinical. The episode explores the following: The key role of the DMPK Project Representative and required knowledge Important concepts that have shaped DMPK drug design such as Physicochemical and application to drug design Free drug theory Human PK prediction, value and uncertainties Modalities  The role of DMPK in reducing drug failure in the clinic  Key individuals that have shaped DMPK science and Kevin's career The future of the DMPK Project Representative and the next generation  Speaker:Kevin Beaumont – Senior Director DMPK, Oncology R&D, AstraZeneca Kevin has worked in the pharmaceutical industry for over 40 years in the fields of drug metabolism and pharmacokinetics, especially as it relates to drug discovery support. His major area of expertise is in the modulation of physicochemistry to affect drug disposition and in prediction of human pharmacokinetics from preclinical information. He is the author of over 50 peer reviewed publications.  Kevin joined the Department of Drug Metabolism at Pfizer Sandwich UK in 1983, directly from his BSC in Biochemistry at the University of London.  Under the mentorship of Dr Dennis Smith Kevin's early career involved developing a fundamental understanding of the basics of DMPK support to discovery and development projects. This included developing expertise in small molecule bioanalysis, completion of radiolabelled ADME studies and direct DMPK support to discovery and development projects.  In 2011, Kevin transferred to Pfizer Inc in Boston Massachusetts, where he was responsible for DMPK/ADME support to the Cardiovascular, Inflammation and Immunology and Rare Disease Therapeutic Areas.  In 2020 Kevin returned to the UK and is currently with AstraZeneca supporting Oncology R&D with DMPK expertise including modalities beyond small molecules. Stay tuned for more podcasts in our Pharmaron DMPK Insights Series!

Simulating the Journey of Oral Medications: A Leap Towards Personalized Medicine  In this episode, we are joined by Deanna Mudie, a senior principal engineer at Lonza, and John DiBella, president of PBPK & Cheminformatics at Simulations Plus, to discuss new techniques in enhancing the bioavailability of drugs.  When you swallow a pill, have you ever pondered the intricate journey it undertakes to deliver its therapeutic effect? This voyage, crucial for the drug's effectiveness, is at the heart of pharmaceutical R&D's quest to enhance bioavailability - the proportion of the drug that enters circulation and reaches the target area.  By simulating how drugs interact with the body, scientists can optimize therapeutic outcomes by tailoring medications to the needs of individual patients. This approach promises a future where drugs are not only more effective but also safer, with reduced side effects. Listen as we delve into the cutting-edge world of Physiologically Based Pharmacokinetic (PBPK) modeling. These computer models integrate factors like gastrointestinal physiology and population characteristics, shedding light on how drugs behave in various body systems without the need for extensive patient testing.   Curious to Know More?  Join us in this conversation hosted by Martina Hestericová with Lonza's Deanna Mudie and Simulations Plus's John DiBella as they unveil the potential of PBPK modeling to revolutionize drug development and personalized medicine.     KEY TERMS IN CONTEXT:  In the context of pharmaceuticals, drug bioavailability refers to the proportion of a drug that enters the circulation when introduced into the body and is thereby able to have an active effect. It's a critical factor in determining the drug's effectiveness, as it measures how much of a drug in a dosage form (like a tablet or injection) becomes available at the target site of action.  PBPK modeling is a sophisticated computational modeling technique used to predict the absorption, distribution, metabolism, and excretion (ADME) of drugs within animals and humans. This approach aids in understanding a drug's bioavailability and supports the design of more effective and safer drug therapies.  Gastrointestinal Physiology refers to the study of the functions and processes of the digestive system or gastrointestinal (GI) tract. In the context of PBPK modeling, understanding gastrointestinal physiology is crucial for predicting how a drug is absorbed into the body, especially for orally administered medications. It includes factors like stomach acid levels, GI transit time, and the surface area available for absorption.  "In silico" refers to the use of computer simulations or digital analyses to conduct experiments or procedures virtually rather than in a laboratory or real-world setting. In silico tools in drug development include software and algorithms used for modeling and simulation, such as PBPK models, which allow researchers to predict how drugs interact with animals and humans, aiding in drug design, testing, and the customization of therapies for personalized medicine. 

This podcast format is inspired by the Charles Dicken's novella “A Christmas Carol” whereby Phil Jeffrey (Bicycle Therapeutics), Beth Williamson (UCB) and Daniel Price (Nimbus) discuss DMPK Past, Present and Future with Scott.  Key elements discussed include the evolution of DMPK as a predictive discipline that links helps the chemistry of drug design with the biology of drug disposition and effect.The episode addresses the following questions:The founding names and principles of DMPK and the emergence of Discovery DMPKToday's use of technologies and in silico modelling and DMPK's role in the 3 pillars/5Rs and PK/PD The outlook for better prediction with advances in AI/MLSpeakers:Phil Jeffrey - Senior Vice President of Preclinical Development at Bicycle TherapeuticsPhil Jeffrey is now semi-retired after contributing to DMPK for over 35 years in the pharmaceutical industry.  Most recently, Phil was Senior Vice President of Preclinical Development at Bicycle Therapeutics and previously has held positions at Pfizer, GlaxoSmithKline, SmithKline Beecham and The Upjohn Company.  Phil is a longstanding contributor the Society for Medicines Research and is an Honorary Professor at the William Harvey Research Institute, Queen Mary University of London.  Phil has a wide breadth of experience across DMPK from, Drug Discovery and early lead optimisation through to clinical proof of mechanism and proof of concept across a wide variety therapeutic areas and drug modalities and made significant contributions to the advancement of understanding the CNS penetration of drugs into the brain. Beth Williamson - Head of ADME in the DMPK group at UCBBeth graduated with a PhD in Pharmacology from the University of Liverpool and is now Head of ADME in the DMPK group at UCB where she also represents DMPK on projects throughout discovery and development. Beth's work has focussed on in vitro and in vivo ADME assay optimisation and validation within drug discovery, particularly to address bespoke questions. Beth has worked in the fields of oncology, neurology and immunology. Her main research interests include drug-drug interactions, extrapolation of pre-clinical in vitro and in vivo data for the prediction of human pharmacokinetics and application of AI/ML approaches within DMPK.  Daniel Price - Vice President of Computational Chemistry & Structural Biology at Nimbus TherapeuticsDr. Daniel Price is Vice President of Computational Chemistry & Structural Biology at Nimbus Therapeutics, where he leads a team of internal and external scientists focused on delivering breakthrough medicines through structure-based design, leveraging both physics-based and knowledge-based predictive modeling.  Before joining Nimbus, he spent 16 years at GlaxoSmithKline, where he led a team of computational chemists and data scientists across diverse areas of structure- and ligand-based drug design, high-content screening analytics, predictive ADME, predictive synthesis, and chemogenomics.  He has led drug discovery programs, contributed to 4 clinical candidates, led the development of GSK's first generation R&D data lake, and authored/co-authored 26 publications.  Dr. Price received his undergraduate degree in chemical engineering from University of Colorado at Boulder followed by his Ph.D. in Molecular Biophysics & Biochemistry from Yale University with Prof. Bill Jorgensen.   He completed an NIH postdoctoral fellowship with Prof. Charlie Brooks, III at The Scripps Research Institute prior to joining GSK. Stay tuned for more podcasts in our Pharmaron DMPK Insights Series!

In this engaging episode, David Hough shared key updates following PaxMedica's recent meeting with the FDA, highlighting pivotal achievements such as: FDA discussion of PaxMedica's data from the PAX-HAT 301 Study and comprehensive nonclinical programs. PAX-HAT-301 study confirmed as positive evidence for African Sleeping Sickness treatment, expected to result in substantial time and resource savings for PaxMedica. FDA acknowledgment of PaxMedica's comprehensive nonclinical program, including safety pharmacology, ADME, and toxicology studies. Waivers granted for the thorough QT/QTc studies, affirming data relevance to the patient population. 2024 NDA submission anticipation underscores PaxMedica's commitment to neglected tropical disease treatments.  

In this engaging episode, David Hough shared key updates following PaxMedica's recent meeting with the FDA, highlighting pivotal achievements such as: FDA discussion of PaxMedica's data from the PAX-HAT 301 Study and comprehensive nonclinical programs. PAX-HAT-301 study confirmed as positive evidence for African Sleeping Sickness treatment, expected to result in substantial time and resource savings for PaxMedica. FDA acknowledgment of PaxMedica's comprehensive nonclinical program, including safety pharmacology, ADME, and toxicology studies. Waivers granted for the thorough QT/QTc studies, affirming data relevance to the patient population. 2024 NDA submission anticipation underscores PaxMedica's commitment to neglected tropical disease treatments.  

Understanding a novel drug's PK and PD properties begins with nonclinical studies and evolves through early phase clinical trials. In this issue, we take a closer look at the collection and use of PK/PD data in early phase drug development. CHAPTERS: - 0:08 — Introduction to Issue 34 - 1:32 — Nonclinical Studies - 2:39 — IND Requirements and Translation to Clinical PK/PD - 5:37 — Translating Nonclinical Knowledge of PK/PD Analyses to Clinical Study - 8:51 — Case Study - 12:32 — Conclusion Click here to read Issue 34: https://www.altasciences.com/sites/default/files/2023-08/the-altascientist-issue-34-toxicokinetics-pharmacokinetics-and-pharmacodynamics.pdf Introduction on TK, PK, and PD Data: The understanding of a new drug's absorption, distribution, metabolism, and excretion (more commonly known as ADME) is critical to ensure that it is safe for human use. That understanding is achieved through collection and analysis of pharmacokinetic (PK) and pharmacodynamic (PD) data, which together account for approximately 25% of the contents of a drug package insert or label. The characterization of PK/PD effects starts with nonclinical toxicokinetic (TK) studies in animals. The purpose of TK studies is to define the chemical properties of the drug, including pharmacology and toxicology, and to assist in development of downstream clinical protocols. The necessary nonclinical studies are conducted before submission of Investigational New Drug (also known as IND) applications to the FDA or other global regulatory agencies, and deliver critical data used to set the parameters for future clinical trials. About Altasciences: Altasciences is an integrated drug development solution company offering pharmaceutical and biotechnology companies a proven, flexible approach to preclinical and clinical pharmacology studies, including formulation, manufacturing, and analytical services. For over 25 years, Altasciences has been partnering with sponsors to help support educated, faster, and more complete early drug development decisions. Altasciences' integrated, full-service solutions include preclinical safety testing, clinical pharmacology and proof of concept, bioanalysis, program management, medical writing, biostatistics, clinical monitoring, and data management, all customizable to specific sponsor requirements. Altasciences helps sponsors get better drugs to the people who need them, faster.

In this episode i bring on ADME teammates tony sanchez and yoshio ortega to talk about the mexican nationals that recently took place. we go over our emotions playing, the vibe of the teams, and overall the impact they left us with and vice versa. take a listen and enjoy

Hoy hablamos de los artefactos que constituyen un hogar como tal, de la nostalgia, y del meteorismo. Admeás como siempre las noticias que ustedes nos envían.

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay. In today's episode I begin my words with the importance of beginnings irrespective to their relevance to time. It is always a good time to begin new, to start afresh!! So all smiles for your wonderful efforts and starts for today! Today's discussion is all about alpha 2 receptor agonists especially highlighted example of the major drug "Clonidine". I will cover it's importance, mechanism, route of administration, ADME profile, effects, uses, adverse effects, etc. In the end wishing fruitful beginnings to your endeavours in order to achieve your set goals and targets and make your wishes true this year '23!! For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!! You can access various links via-https://linktr.ee/ispharmacologydifficult Please leave Review on Apple podcasts! Connect on Twitter & Instagram! My books on Amazon & Goodreads!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay.In today's episode I begin my words with the importance of beginnings irrespective to their relevance to time. It is always a good time to begin new, to start afresh!!So all smiles for your wonderful efforts and starts for today!Today's discussion is all about alpha 2 receptor agonists especially highlighted example of the major drug "Clonidine". I will cover it's importance, mechanism, route of administration, ADME profile, effects, uses, adverse effects, etc.In the end wishing fruitful beginnings to your endeavours in order to achieve your set goals and targets and make your wishes true this year '23!!For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also.You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT".If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!You can access various links via-https://linktr.ee/ispharmacologydifficultPlease leave Review on Apple podcasts!Connect on Twitter & Instagram!My books on Amazon & Goodreads!

Designing new compounds to be used as therapeutics is a challenge regardless of the approach. Artificial intelligence shows promise for solving some of those challenges, whether it's identifying a hit, lead optimization or something else. Ashwini Ghogare is the intrapreneur CEO of Artificial Intelligence and Automation in Drug Discovery at Millipore Sigma. She was kind enough (and patient enough) to educate me on how AI can be used to help with figuring out the synthesis of new compounds and even predicting ADME or physical chemical properties.When I look at complex molecules, I'm overwhelmed just imagining how they are synthesized, given that some groups may be cross-reactive etc. How do ensure that you get (mostly) what you intend to make? I learned a little bit about the possibilities in this conversation, for example, synthesizing component groups as opposed to a linear process from start to finish. (The only real synthesis I've ever done was a 13-base oligonucleotide -in a fume hood!- long before that were done by machine.) In the early stages, you just want to see if a molecule can be made and will it do what you want. Someone else gets the job of figuring out how to make it efficiently at scale.If you like this content, you probably know someone else who will also.Thanks.Back to predicting ADME properties: Making drugs is expensive. Most will fail. But if we knew in advance a little more about the ADME properties we might expect, we might at least reduce the cost of development a bit.The big challenge here is that, compared to finance or my YouTube habits, the amount of data available for training models is limited to none. The publicly available data is all from published studies. But to train a model well, it would be really valuable to have negative data in the training set.Merch KGAa are leading the way for their peers in the industry to take advantage of sharing datasets for training without actually sharing or compromising the actual underlying data.Data can be negative or drugs can fail for many reasons. Ashwini points out that one step in the right direction to address this is automation, removing at least some sources of error. When I asked her what the future of drug development looks like I was blown away by her answer. She envisions a world where compounds are not just synthesized by automation, but where those machines are autonomous! The machines analyze the data from the synthesized compounds and iterate independently from there.I'm essentially going to school on this podcast. If you are learning also or know someone else who would benefit, please subscribe and share.Ashwini on LinkedInChat with Chris about content for your life science brand This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit cclifescience.substack.com

Phil Carroll and Kevin Hornsby review the week that was in small cap stocks and general market news. #BEN is talked about at length and the commodities sector is analysed. Other companies mentioned (in no particular order) #GGP #BEN #KIBO #AFP #GLR #GRIT #SPEC #EST #MILA #AML  #CHLL #PRD #HARL #MAST#ARV #ADME #PXEN #JLP #ARV #XTR #MADE #VELA Disclaimer & Declaration of Interest The information, investment views, and recommendations in this podcast are provided for general information purposes only. Nothing in this podcast should be construed as a solicitation to buy or sell any financial product relating to any companies under discussion or to engage in or refrain from doing so or engaging in any other transaction. Any opinions or comments are made to the best of the knowledge and belief of the commentator but no responsibility is accepted for actions based on such opinions or comments. The commentators may or may not hold investments in the companies under discussion.

A new research paper was published in Oncotarget's Volume 13 on November 2, 2022, entitled, “MK256 is a novel CDK8 inhibitor with potent antitumor activity in AML through downregulation of the STAT pathway.” Acute myeloid leukemia (AML) is the most lethal form of AML due to disease relapse. Cyclin dependent kinase 8 (CDK8) is a serine/threonine kinase that belongs to the family of Cyclin-dependent kinases and is an emerging target for the treatment of AML. MK256, a potent, selective, and orally available CDK8 inhibitor was developed to target AML. In this new study, researchers Jen-Chieh Lee, Shu Liu, Yucheng Wang, You Liang, and David M. Jablons from the University of California San Francisco and Touro University sought to examine the anticancer effect of MK256 on AML. “In CD34+/CD38- leukemia stem cells, we found that MK256 induced differentiation and maturation.” Treatment of MK256 inhibited proliferation of AML cell lines. Further studies of the inhibitory effect suggested that MK256 not only downregulated phosphorylated STAT1(S727) and STAT5(S726), but also lowered mRNA expressions of MCL-1 and CCL2 in AML cell lines. Efficacy of MK256 was shown in MOLM-14 xenograft models, and the inhibitory effect on phosphorylated STAT1(S727) and STAT5(S726) with treatment of MK256 was observed in vivo. Pharmacologic dynamics study of MK256 in MOLM-14 xenograft models showed dose-dependent inhibition of the STAT pathway. Both in vitro and in vivo studies suggested that MK256 could effectively downregulate the STAT pathway. In vitro ADME, pharmacological kinetics, and toxicity of MK256 were profiled to evaluate the drug properties of MK256. “Our results show that MK256 is a novel CDK8 inhibitor with a desirable efficacy and safety profile and has great potential to be a promising drug candidate for AML through regulating the STAT pathway.” DOI: https://doi.org/10.18632/oncotarget.28305 Correspondence to: Jen-Chieh Lee -jenchieh.lee@ucsf.edu, Shu Liu - shu.liu@ucsf.edu Keywords: AML, CDK8, kinase inhibitor, STAT pathway, xenograft Video: https://www.youtube.com/watch?v=8bRgqTg9-c8 About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com

Phil Carroll and Kevin Hornsby talk to Osa about the Aje and Barracuda Interests. Disclaimer & Declaration of Interest The information, investment views, and recommendations in this podcast are provided for general information purposes only. Nothing in this podcast should be construed as a solicitation to buy or sell any financial product relating to any companies under discussion or to engage in or refrain from doing so or engaging in any other transaction. Any opinions or comments are made to the best of the knowledge and belief of the commentator but no responsibility is accepted for actions based on such opinions or comments. The commentators may or may not hold investments in the companies under discussion.

This week on Lawfare's Arbiters of Truth series on disinformation, Alina Polyakova and Quinta Jurecic spoke with Lisa Kaplan and Sophie Lawton of Alethea Group, an organization that works to detect and mitigate disinformation on social media. Lisa recently published a piece on Lawfare about a massive network of companies run by TheSoul Publishing—founded in Russia by a company called AdMe. The companies publish bizarre craft videos on Youtube and Facebook, along with a handful of videos about history and politics with an overtly pro-Russian slant. So what is actually going on here? They talked about what red flags Lisa and Sophie look for in hunting down disinformation, their experiences tackling disinformation while working for Senator Angus King's reelection campaign in 2018, and how political campaigns need to tackle online influence efforts in 2020. See acast.com/privacy for privacy and opt-out information.

Taking an assay from bench to an automated platform In this podcast, Prakash Bhosale (Director of Discovery ADME at Q2 Solutions; IN, USA) discusses high-throughput in vitro screening and how to understand structure-activity relationships against ADME properties. The advantages of the Tecan technology are also addressed as well as top tips for driving SAR analysis. Questions discussed include: Why is compound management and storage important? Do you suggest that a lab goes full in on automation or transitions to automation over time? When do you take an assay from the bench to an automated platform? How much experience do you need with programming to implement automated tools? What are the advantages of the Tecan technology? What are your top tips for driving SAR analysis?

Automation of ADME: a podcast with Prakash Bhosale by Future Science Group

Higher omega-3 levels linked with lower risk of death during 16-year period The Fatty Acids and Outcomes Research Consortium, April 28 2021.    An analysis of prospective studies published on April 22, 2021 in Nature Communications uncovered a decreased risk of mortality during an average of 16 years among men and women who had higher red blood cell or plasma levels of omega-3 fatty acids.  The analysis was conducted by William S. Harris and The Fatty Acids and Outcomes Research Consortium (FORCE). Dr Harris is a codeveloper of the Omega-3 Index, which measures omega 3 levels in red blood cell membranes. The team examined 17 prospective studies that evaluated associations between the risk of death from all causes and levels of the omega-3 fatty acids alpha linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and EPA plus DHA.  During the studies’ follow-up periods, 15,720 deaths occurred among a total of 42,466 men and women. Subjects whose EPA, DPA, DHA, and EPA plus DHA levels were among the top 10% of participants experienced a 9% to 13% reduction in mortality from all causes during follow-up compared to men and women whose levels were among the lowest 10%. When cause-specific mortality was examined, having EPA, DPA, DHA, or EPA plus DHA levels among the highest 10% was associated with a lower risk of cardiovascular mortality, cancer mortality and mortality from all other causes combined (with the exception of the association between DHA and reduced cancer mortality, which was not considered significant).  "Since all of these analyses were statistically adjusted for multiple personal and medical factors (i.e., age, sex, weight, smoking, diabetes, blood pressure, etc., plus blood omega-6 fatty acid levels), we believe that these are the strongest data published to date supporting the view that over the long-term, having higher blood omega-3 levels can help maintain better overall health," Dr Harris concluded.     New study shows tree nuts may play a role in both weight loss and weight maintenance   University of California at Los Angeles, May 4, 2021  In a randomized, controlled study* published online in the journal, Nutrients, researchers found that including mixed tree nuts in a weight management program resulted in significant weight loss and improved satiety. Researchers at UCLA compared 95 overweight/obese men and women (BMI 27.0-35.0 kg/m2) ages 30-68 years who consumed either 1.5 ounces of mixed tree nuts or a pretzel snack. Both snacks provided the same number of calories, as part of a hypocaloric weight loss diet (500 calories less than resting metabolic rate) over 12 weeks. This was followed by an isocaloric weight maintenance program for an additional 12 weeks.  Participants experienced significant weight loss (12 weeks: -1.6 kg and -1.9 kg and 24 weeks: -1.5 kg and -1.4 kg) in the tree nut and pretzel snack groups, respectively. Both groups also showed a significant decrease in BMI at 12 weeks, compared to baseline. However, satiety was significantly higher at the end of week 24 in the mixed tree nut group, and there was a trend toward greater weight maintenance compared to the pretzel group. Moreover, the dropout rate was significantly lower in the mixed tree nut group (16.4%) compared to the pretzel (35.9%) group. And, heart rate was decreased significantly, compared to baseline, in those consuming tree nuts, but not pretzels.  "Tree nuts (almonds, Brazil nuts, cashews, hazelnuts, macadamias, pecans, pine nuts, pistachios and walnuts) are a great source of protein, healthy fats and fiber," explained lead researcher, Zhaoping Li, MD, PhD, Professor of Medicine and Chief of the Division of Clinical Nutrition at UCLA. "This makes them so satiating and may be a major reason why we saw less weight gain in the tree nut group during weight maintenance, and a significantly lower dropout rate compared to the pretzel group."  Recent research has shown that more than 40 percent of Americans are overweight or obese.** During the past year many Americans have gained weight while sheltering in place, partly due to less exercise and more snacking. One study estimates a weight gain of 1.5 pounds per month.*** "We know most people get about 25% of their calories each day from snacks and a large proportion come from desserts, sugar-sweetened beverages, sweets and salty snacks," states Dr. Li. "By replacing just one of those snacks with 1.5 ounces of tree nuts may result in a positive impact on weight and overall health." According to Maureen Ternus, M.S., R.D.N, Executive Director of the International Tree Nut Council Nutrition Research & Education Foundation (INC NREF), "This latest study adds to a growing body of evidence showing that nut consumption may be a useful tool in weight management."     Green tea compound and coconut oil may help improve depression in multiple sclerosis patients Catholic University of Valencia (Spain), April 30. 2021   According to news reporting originating from Valencia, Spain, research stated, “Multiple sclerosis (MS) is pathogenically characterized by high oxidative stress and symptomatically by progressive muscle loss and increased body fat associated with the presence of depression. Epigallocatechin gallate (EGCG) (particularly present in green tea) and ketone bodies (in particular beta-hydroxybutyrate (BHB)), whose main source is coconut oil, have shown emotional benefits and body fat loss.” The news journalists obtained a quote from the research from Catholic University of Valencia: “The aim of this study was to assess the impact of EGCG and coconut oil on cortisol activity related to fat loss and depression in MS patients. The study involved 51 MS patients who were randomly divided into an intervention group or a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, which were included in their daily diet for four months. The control group received placebo and all patients followed an isocaloric diet. A blood sample was collected before and after the four-month period, and levels of cortisol, albumin and BHB were measured in serum. In addition, immediately before and after the intervention, anthropometric variables were measured: waist-to-hip ratio (WHR), body fat mass percentage, fat weight, total weight, and muscle mass percentage. Depression was assessed with the Beck Depression Inventory II (BDI-II). No significant changes were obtained in cortisol levels in any of the groups, and there was a significant increase in albumin in the blood of the intervention group only that could lead to a decrease in serum free cortisol. In addition, it was observed a significant decrease in levels of depression and abdominal fat.” According to the news reporters, the research concluded: “EGCG combined with coconut oil increase the concentration of albumin in blood and produce less depression in MS patients.”       Vulnerable older people at greater risk of depression and anxiety during pandemic   University of Manchester (UK), May 5, 2021 Older people who are clinically vulnerable to COVID-19 are at greater risk of deterioration in health and social well-being during the pandemic, according to a new study. The research, published in the Journal of Epidemiology and Community Health, found that older people were more likely to report worse health outcomes than those with no clinical vulnerabilities, including greater depression and anxiety and lower quality of life, even when taking into account pre-pandemic levels of health and social well-being. The findings highlight the need for policymakers to consider the mental and physical health consequences of the pandemic for those at higher risk from coronavirus, particularly for those asked to shield. Professor Debora Price from The University of Manchester and Dr. Giorgio Di Gessa from UCL compared data from 2020's English Longitudinal Study of Aging with data from the previous year. They analyzed responses from over 5000 people aged 52 and over in private households in England. The study revealed that during the pandemic, respondents classified as clinically vulnerable were more likely to report poor self-rated health, lower levels of physical activity, depression, anxiety, lower quality of life as well as loneliness and receipt of care, compared to those without clinical vulnerabilities. This was true within each age group. Among people in their 70s, the odds of being depressed and anxious for those clinically vulnerable were around 50% higher than for those without clinical vulnerabilities. Those in their 80s—regardless of clinical vulnerability—were much more likely to have unmet care needs and to have little contact with friends and family by text, email, or videocall. Although older adults' health and social well-being have been impacted by shielding, the researchers found that it was those who were clinically vulnerable and shielding who reported the most substantial rises in anxiety, depression, poor self-rated health and receipt of formal care, as well as decreases in well-being and physical activity. "Older people with underlying health conditions, even before the pandemic, faced challenges in terms of access to healthcare services and social contact," said Professor Debora Price. "They also experienced greater emotional distress, higher risk of loneliness and poorer quality of life than non-vulnerable individuals." "While policies focusing on shielding clinically vulnerable older people reduce rates of hospitalization and death from COVID-19, policymakers need to acknowledge that there may be adverse consequences of this measure and address the wider needs of these vulnerable groups," added Dr. Giorgio Di Gessa. "It's vital that policymakers are aware that when advised to stay at home, a host of health and social risks for this group, already poor, are likely to be exacerbated."   Researchers find obesity linked to reduced blood flow to the brain Trinity College Dublin (Ireland), May 5, 2021 A new study from scientists at The Irish Longitudinal Study on Aging (TILDA) at Trinity College Dublin reveals important findings, indicating that being overweight or obese significantly reduces blood flow in the brain. The study also shows that increased physical activity can positively modify, or even negate, this reduction in brain blood flow. The study contains relevant information which is of great interest to the general public; since reduced blood flow in the brain, or 'cerebral hypoperfusion," is an early mechanism in vascular dementia and Alzheimer's disease. Obesity and health challenges According to the World Health Organization (WHO), obesity is a worsening health crisis that has reached epidemic proportions globally, with over 1 billion adults overweight—and at least 300 million clinically obese. It continues to be a major contributor to global rates of chronic disease and disability, affecting overall quality of life, while placing increased strain on the immune system which is of the upmost importance given the current COVID-19 situation. Obesity is also a significant public health concern given its negative impact on physiological function, especially as we age. Finding easily implemented and cost-effective ways to tackle the impact of obesity is particularly important to help protect against negative health outcomes in later life. What are the findings of the TILDA study? The study investigates three different measures of obesity—body mass index (BMI), waist-to-hip ratio and waist circumference, as well as physical activity, in adults over 50 years. Brain blood flow was measured using cutting-edge MRI scanning and analysis techniques. The findings reveal that being overweight or obese is associated with reduced blood supply to the brain. Whereas brain blood flow is known to decline with age, in this study the negative influence of obesity on brain blood flow was shown to be greater than that of age. However, being physically active helps to cancel out the negative effects of obesity on brain blood flow. Key Findings ncreased BMI, waist-to-hip ratio, and waist size are associated with less blood supply to the brain. A waist size increase of +1cm is associated with the same reduction in brain blood flow as +1 year of age. Higher levels of physical activity modify the associations between reduced brain blood flow and obesity. Recommendations The study recommends at least 1.5 to two hours of 'being active' throughout the day, engaging in activities that require moderate effort. These include activities that cause one to breathe harder than normal, such as fast walking or cycling. However, any increase in physical activity, particularly if integrated into daily or weekly habits, such as gardening, should help maintain and potentially improve brain blood flow. Dr. Silvin Knight, Research Fellow at TILDA and lead author, said: Consistent, healthy blood supply to the brain is critical, as it ensures that the brain is provided with enough oxygen and nutrients to function correctly. If brain blood flow becomes impaired, it can lead to serious health issues as we age, such as increasing the risk of dementia and Alzheimer's disease. We know that obesity can predispose a person to age-related conditions, illness, and disease, and even reduce life expectancy by up to six years in men and seven years in women, after the age of forty. Our study reveals clear associations between obesity and reduced blood supply to the brain in an older population. The study also shows the importance of being physically active for older overweight or obese individuals, as this may help to protect against reduced brain blood flow and the poor health outcomes that can arise from this. Professor Rose Anne Kenny, Principal Investigator of TILDA, and co-author of the study, said: "Many experts have shown that obesity and aging have very similar effects on the biology of aging; diseases associated with obesity are similar to those of aging and age-related diseases—heart disease, diabetes, high blood pressure, kidney failure, arthritis, susceptibility to infections- including COVID-19." Our study not only shows that there is a link between obesity and reduced brainblood flow, but also that it is possible to protect against the negative consequences of obesity through regular physical exercise. Whereas these findings are of relevance in the global context, because of the rapidly evolving global burden of obesity, the research is especially important to Irish adults because obesity and being overweight is a considerable health issue in Ireland. Previous TILDA research has shown that over one-third of Irish adults aged 50 and older are obese and a further 43% overweight. As we prepare our society for a growing aging population, we can use this evidence to prepare meaningful public health policies that will promote impactful and positive lifestyle habits, such as regular physical activity, to mitigate against some of the negative consequences of the growing obesity crisis.           In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus Shanghai Health Commission Key Lab of Artificial Intelligence (AI)-Based Management of Inflammation and Chronic Diseases, May 2, 2021 Objective In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel coronavirus (2019-nCoV), an ongoing novel coronavirus that causes pneumonia. Methods There were two main steps in the screening process. In the first step we conducted a literature search for natural compounds that had been biologically confirmed as against sever acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus. Resulting compounds were cross-checked for listing in the Traditional Chinese Medicine Systems Pharmacology Database. Compounds meeting both requirements were subjected to absorption, distribution, metabolism and excretion (ADME) evaluation to verify that oral administration would be effective. Next, a docking analysis was used to test whether the compound had the potential for direct 2019-nCoV protein interaction. In the second step we searched Chinese herbal databases to identify plants containing the selected compounds. Plants containing 2 or more of the compounds identified in our screen were then checked against the catalogue for classic herbal usage. Finally, network pharmacology analysis was used to predict the general in vivo effects of each selected herb. Results Of the natural compounds screened, 13 that exist in traditional Chinese medicines were also found to have potential anti-2019-nCoV activity. Further, 125 Chinese herbs were found to contain 2 or more of these 13 compounds. Of these 125 herbs, 26 are classically catalogued as treating viral respiratory infections. Network pharmacology analysis predicted that the general in vivo roles of these 26 herbal plants were related to regulating viral infection, immune/inflammation reactions and hypoxia response. Conclusion Of course, it should be pointed out that Chinese herbs that have not been identified through this screening process may still have beneficial effects. Further, considering that the biologically validated natural compounds reported in the literature cannot cover all antiviral natural compounds, and the natural compounds included in the Chinese medicine database are not complete, the process that we have followed may have excluded herbs that would be well suited to this treatment. Nevertheless, the purpose of this screening was to provide a rational approach for selecting Chinese herbal medicines with a high potential efficacy in treating 2019-nCoV and related viruses. The specific dosage and usage of each herb should be determined based on patients’ manifestations. Finally, the key step in this screening was molecular docking. The 3D structures of the proteins used here are based on reported gene sequences. If the virus mutates during transmission, a new screening is recommended. In conclusion, this work has identified several Chinese medicinal plants classified as antiviral/pneumonia-effective that might directly inhibit the novel coronavirus, 2019-nCoV. Additionally, we propose screening principles and methods which may provide guidance in screening antiviral drugs from other natural drug databases.     Ginkgolide B monotherapy reverses osteoporosis by regulating oxidative stress-mediated bone homeostasis   Chinese University of Hong Kong, May 4, 2021 According to news reporting from Hong Kong, People’s Republic of China, research stated, “Osteoporosis is characterized by reductions in bone mass, which could be attributed to the dysregulation of bone homeostasis, such as the loss of balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Elevated levels of oxidative stress increase bone resorption by promoting osteoclastogenesis and inhibiting the osteogenesis.” The news correspondents obtained a quote from the research from the Chinese University of Hong Kong, “Ginkgolide B (GB), a small natural molecule from Ginkgo biloba, has been reported to possess pharmacological activities by regulating reactive oxygen species (ROS) in aging-related degenerative diseases. Herein, we assessed the therapeutic effects of GB on the bone phenotypes of mice with osteoporosis induced by (I) aging, (II) ovariectomy, and (III) glucocorticoids. In all three animal models, oral gavage of GB significantly improved bone mass consistent with the increase in the OPG-to-RANKL ratio. In the in vitro experiments, GB promoted osteogenesis in aged mesenchymal stem cells (MSCs) and repressed osteoclastogenesis in aged macrophages by reducing ROS. The serum protein profile in GB-treated aged mice revealed moderate rejuvenating effects; signaling pathways associated with ROS were also regulated. The anabolic and anti-catabolic effects of GB were illustrated by the reduction in ROS. Our results indicate that GB is effective in treating osteoporosis.” According to the news reporters, the research concluded: “The use of GB in patients with osteoporosis is worthy of further clinical investigation.” This research has been peer-reviewed.

Part 1 of a full review of pharmacology for the dental hygienist. Topics include: the nervous system-parasympathetic & sympathetic, drug administration (ADME), vasoconstrictors, dental anesthesia, opioids & non opioids

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay.Its Sunday Matinee time and I am not the audience, but the host, As I steal a few moments from your precious day's time, I engrave and inscribe your lockdown diaries and learning via the chisel of my tongue.In today's episode I will be talking about "A" of the "ADME" study, it stands for absorption!I will broadly cover the little introductory part and then the basic determinants of absorption like area of absorption, vascularity, concentration gradient, routes of drug administration , etc and yes a little detail of each one. Few tricky things will be laid emphasis on and they will be made to learn by rote by you! Isn't that wonderful. With the idea of keeping my talks short and light for the weekend, as the clock hits wind'o clock, I will leave you with a tune riddle to solve of my recent favorite melody, just guess the renowned artist, Na...Na....Na....Na.......Na...... For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay.Its Sunday Matinee time and I am not the audience, but the host, As I steal a few moments from your precious day's time, I engrave and inscribe your lockdown diaries and learning via the chisel of my tongue.In today's episode I will be talking about "A" of the "ADME" study, it stands for absorption!I will broadly cover the little introductory part and then the basic determinants of absorption like area of absorption, vascularity, concentration gradient, routes of drug administration , etc and yes a little detail of each one. Few tricky things will be laid emphasis on and they will be made to learn by rote by you! Isn't that wonderful. With the idea of keeping my talks short and light for the weekend, as the clock hits wind'o clock, I will leave you with a tune riddle to solve of my recent favorite melody, just guess the renowned artist, Na...Na....Na....Na.......Na...... For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay. Its Sunday Matinee time and I am not the audience, but the host, As I steal a few moments from your precious day's time, I engrave and inscribe your lockdown diaries and learning via the chisel of my tongue. In today's episode I will be talking about "A" of the "ADME" study, it stands for absorption! I will broadly cover the little introductory part and then the basic determinants of absorption like area of absorption, vascularity, concentration gradient, routes of drug administration , etc and yes a little detail of each one. Few tricky things will be laid emphasis on and they will be made to learn by rote by you! Isn't that wonderful. With the idea of keeping my talks short and light for the weekend, as the clock hits wind'o clock, I will leave you with a tune riddle to solve of my recent favorite melody, just guess the renowned artist, Na...Na....Na....Na.......Na...... For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay.In today's episode i will be commencing my talks upon Pharmacokinetics, the dreaded one!! But no worries, we will inaugarate the conversation in too simple way just good enough to settle in your minds highly simplified everything! First comes the definition, then basic concepts, ideas, rules of the theory of pharmacokinetics. It is famous as the ADME study, I will be giving little details about it then before actually diving deep in this sea, we will have a short walk along the shores as we discuss the audio diagrammatic representation of the whole pharmacokinetic process in nutshell! Then a word about the Biological membranes, their unique, specific structure and much more. I will be telling you important process about drug transport and how the diffusion concepts are related to membrane structure, all this comes into play in today's episode! For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay. In today's episode i will be commencing my talks upon Pharmacokinetics, the dreaded one!! But no worries, we will inaugarate the conversation in too simple way just good enough to settle in your minds highly simplified everything! First comes the definition, then basic concepts, ideas, rules of the theory of pharmacokinetics. It is famous as the ADME study, I will be giving little details about it then before actually diving deep in this sea, we will have a short walk along the shores as we discuss the audio diagrammatic representation of the whole pharmacokinetic process in nutshell! Then a word about the Biological membranes, their unique, specific structure and much more. I will be telling you important process about drug transport and how the diffusion concepts are related to membrane structure, all this comes into play in today's episode! For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay.In today's episode i will be commencing my talks upon Pharmacokinetics, the dreaded one!! But no worries, we will inaugarate the conversation in too simple way just good enough to settle in your minds highly simplified everything! First comes the definition, then basic concepts, ideas, rules of the theory of pharmacokinetics. It is famous as the ADME study, I will be giving little details about it then before actually diving deep in this sea, we will have a short walk along the shores as we discuss the audio diagrammatic representation of the whole pharmacokinetic process in nutshell! Then a word about the Biological membranes, their unique, specific structure and much more. I will be telling you important process about drug transport and how the diffusion concepts are related to membrane structure, all this comes into play in today's episode! For all the updates and latest episodes of my podcast, please visit www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast ! I am Dr Radhika Vijay, if you are wondering what are the most broad and basic divisions of the subject Pharmacology, you will find it all in today's episode. Broadly, Pharmacology can be divided into Pharmacodynamics and Pharmacokinetics. Pharmacodynamics covers all details and lets us know ," What the drug does to the body?" On the other hand, Pharmacokinetics is the ADME study, it covers complete drug movement inside the body, telling about all the four processes in detail, Absorption, Distribution , Metabolism and Excretion. All in all, we get to know, "What body does to the drug?" With the help of two examples for each of these divisions, I will clearly describe the whole description and points. After telling you all about these broad pharmacological divisions, I will be throwing light on the Golden connection of Pharmaceutics, Pharmacokinetics, Pharmacodynamics and Pharmacotherapeutics. Its a chain connection step by step with a wonderful description so that you can memorize nicely and understand. fully. On this point of discussion, your query is definite to arise about other branches discussion which you know or you have. ever heard about. Well, no worries, with a promise to lighten up next school of thought with details about other branches, I will humbly depart today. For all updates and latest episodes, please visit www.ispharmacologydifficult.com. You can follow me on social media handles like twitter, insta, facebook and linkedin all with same names"Is Pharmacology Difficult". If you are listening for the first time, do follow me here on your favourite platform, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast ! I am Dr Radhika Vijay, if you are wondering what are the most broad and basic divisions of the subject Pharmacology, you will find it all in today's episode. Broadly, Pharmacology can be divided into Pharmacodynamics and Pharmacokinetics. Pharmacodynamics covers all details and lets us know ," What the drug does to the body?" On the other hand, Pharmacokinetics is the ADME study, it covers complete drug movement inside the body, telling about all the four processes in detail, Absorption, Distribution , Metabolism and Excretion. All in all, we get to know, "What body does to the drug?" With the help of two examples for each of these divisions, I will clearly describe the whole description and points. After telling you all about these broad pharmacological divisions, I will be throwing light on the Golden connection of Pharmaceutics, Pharmacokinetics, Pharmacodynamics and Pharmacotherapeutics. Its a chain connection step by step with a wonderful description so that you can memorize nicely and understand. fully. On this point of discussion, your query is definite to arise about other branches discussion which you know or you have. ever heard about. Well, no worries, with a promise to lighten up next school of thought with details about other branches, I will humbly depart today. For all updates and latest episodes, please visit www.ispharmacologydifficult.com. You can follow me on social media handles like twitter, insta, facebook and linkedin all with same names"Is Pharmacology Difficult". If you are listening for the first time, do follow me here on your favourite platform, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast ! I am Dr Radhika Vijay, if you are wondering what are the most broad and basic divisions of the subject Pharmacology, you will find it all in today's episode. Broadly, Pharmacology can be divided into Pharmacodynamics and Pharmacokinetics. Pharmacodynamics covers all details and lets us know ," What the drug does to the body?" On the other hand, Pharmacokinetics is the ADME study, it covers complete drug movement inside the body, telling about all the four processes in detail, Absorption, Distribution , Metabolism and Excretion. All in all, we get to know, "What body does to the drug?" With the help of two examples for each of these divisions, I will clearly describe the whole description and points. After telling you all about these broad pharmacological divisions, I will be throwing light on the Golden connection of Pharmaceutics, Pharmacokinetics, Pharmacodynamics and Pharmacotherapeutics. Its a chain connection step by step with a wonderful description so that you can memorize nicely and understand. fully. On this point of discussion, your query is definite to arise about other branches discussion which you know or you have. ever heard about. Well, no worries, with a promise to lighten up next school of thought with details about other branches, I will humbly depart today. For all updates and latest episodes, please visit www.ispharmacologydifficult.com. You can follow me on social media handles like twitter, insta, facebook and linkedin all with same names"Is Pharmacology Difficult". If you are listening for the first time, do follow me here on your favourite platform, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.11.378083v1?rss=1 Authors: Ahmed, S. R., Banik, A., Anni, S. M., Chowdhury, M. M. H. Abstract: The ZIKA virus has caused a heavy concern everywhere the globe because of its high infectivity and mortality rate. Still, there's no specific drug or preventive medication to treat ZIKA infection despite comprehensive analysis by the researchers. This study was designed to demonstrate the efficacy of some plant derived bioactive compounds against ZIKV by using both structure and ligand based virtual screening methods. A number of 35 plant metabolites were screened against ZIKA NS2B-NS3 protease (5LC0), Envelop protein (5JHM), Capsid protein (5YGH) and NS5 RNA-dependent RNA polymerase protein (5U04) employing molecular docking approach. Results showed that there have been four metabolites, i.e. Chicoric acid, Luteone, Reserpine and Rosmarinic acid provide highest binding affinity to targeted ZIKV proteins. Crucial binding sites and drug surface hotspots are unraveled for every targeted viral protein. The ADME study showed that neither of the candidate compounds had side effects that would reduce their drug-like properties. As compared, the toxicity pattern analysis has unmasked the non-toxic essence of top drug candidates. The RMSD values of ligand-macromolecule complexes were 2 Angstrom apart from Envelop protein- Chicoric Acid, although the RMSF values showed normal atomic fluctuations within the molecular dynamics analysis, with the exception of Envelop protein- Chicoric Acid. The expected majority of the target class the highest drug candidates is enzyme classes (e.g. protease, hydrolase, phosphatase). In addition, the drug similarity prediction revealed several structural analogs from drugbank such as Isoformononetin (DB04202), Deserpidine (DB01089) and Rescinnamine (DB01180) etc. and these analogs could even be an option for the treatment of ZIKV infections. The study can pave the way for the creation of effective ZIKV medications and preventive measures. We highly recommend further in vivo trials for the experimental validation of our findings. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.19.345975v1?rss=1 Authors: Banik, A., Ahmed, S. R., Sajib, E. H., Deb, A., Sinha, S., Azim, K. F. Abstract: The deeper understanding of metastasis phenomenon and detection of drug targets could be a potential approach to minimize cancer mortality. In this study, attempts were taken to unmask novel therapeutics to prevent metastasis and cancer progression. Initially, we explored the physiochemical, structural and functional insights of three metastasis tumor antigens (MTAs) and evaluated some plant based bioactive compounds as potent MTA inhibitors. From 50 plant metabolites screened, isoflavone, gingerol, citronellal and asiatic acid showed maximum binding affinity with all three MTA proteins. The ADME analysis detected no undesirable toxicity that could reduce the drug likeness properties of top plant metabolites. Moreover, molecular dynamics studies revealed that the complexes were stable and showed minimum fluctuation at molecular level. We further performed ligand based virtual screening to identify similar drug molecules using a large collection of 3,76,342 compounds from DrugBank. The results suggested that several structural analogs (e.g. Tramadol, Nabumetone, DGLA, Hydrocortisone) may act as agonist to block the MTA proteins and inhibit cancer progression at early stage. The study could be useful to develop effective medications against cancer metastasis in future. Due to encouraging results, we highly recommend further in vitro and in vivo trials for the experimental validation of the findings. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.25.266361v1?rss=1 Authors: De Leo, F., Giacomo, Q., De Marchis, F., Malisa, M. V., Bianchi, M. E., Musco, G. Abstract: HMGB1 is a key molecule that both triggers and sustains inflammation following infection or injury, and is involved in a large number of pathologies, including cancer. HMGB1 participates to the recruitment of inflammatory cells forming a heterocomplex with the chemokine CXCL12 (HMGB1/CXCL12), herewith activating the G-protein coupled receptor CXCR4. Thus, identification of molecules that disrupt this heterocomplex can offer novel pharmacological opportunities to treat inflammation related diseases. To identify new HMGB1/CXCL12 inhibitors we have performed a study on the ligandability of the single HMG boxes of HMGB1 followed by a virtual screening campaign on both HMG boxes using Zbc Drugs and three different docking programs (Glide, AutoDock Vina, AutoDock 4.2.6). The best poses in terms of scoring functions, visual inspection and predicted ADME properties were further filtered according to a pharmacophore model based on known HMGB1 binders and clustered according to their structures. Eight compounds representative of the clusters were tested for HMGB1 binding by NMR. We identified 5,5' methylenedi-2,3-cresotic acid (2a) as binder of both HMGB1 and CXCL12; 2a also targets the HMGB1/CXCL12 heterocomplex. In cell migration assays 2a inhibited the chemotactic activity of HMGB1/CXCL12 with IC50 in the subnanomolar range, the best documented up to now. These results pave the way for future structure activity relationship studies to optimize the pharmacological targeting of HMGB1/CXCL12 for anti-inflammatory purposes. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.20.106260v1?rss=1 Authors: Premasiri, A. S., Gill, A. L., Vieira, F. G. Abstract: The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a repeat expansion mutation in the C9orf72 gene. Repeat-associated non-AUG (RAN) translation of this expansion produces five species of dipeptide repeat proteins (DRPs). The arginine containing DRPs, polyGR and polyPR, are consistently reported to be the most toxic. Here, we uncover Type I protein arginine methyltransferase (PRMT) inhibitors as possible therapeutics for polyGR- and polyPR- related toxicity. Furthermore, we reveal data that suggest that asymmetric dimethylation (ADMe) of polyGR is a determining factor in its pathogenesis. Copy rights belong to original authors. Visit the link for more info