Podcasts about Metabolite

Intermediate or end product of metabolism

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Best podcasts about Metabolite

Latest podcast episodes about Metabolite

nf-cast - the bioinformatics podcast
Episode 50: Imaging pipelines and analysis, with Krešimir Beštak

nf-cast - the bioinformatics podcast

Play Episode Listen Later Apr 4, 2025 34:32


In this milestone 50th episode of the Nextflow podcast, host Phil Ewels sits down with Krešimir Beštak, a PhD student and active contributor to the nf-core community, to explore an exciting frontier in bioinformatics: microscopy and spatial omics.While Nextflow is traditionally associated with genomics workflows, Krešimir shares how it's being used to power image analysis pipelines like MCMICRO, supporting complex research into cardiovascular disease and cancer diagnostics. Based at the University Hospital Heidelberg, Krešimir discusses his transition from master's student to PhD researcher, the translational applications of spatial proteomics, and how Nextflow enables reproducible workflows far beyond its original scope.00:00 Podcast Ep 50: Krešimir00:09 Welcome and introductions03:13 Introduction to Spatial Omics04:26 Multiplexing markers06:38 Metabolite microscopy07:23 Myocardial multiomics08:58 Microscopy data analysis11:32 nf-core/mcmicro13:05 2D vs 3D microscopy13:38 Computational bottlenecks within analysis15:43 Other nf-core imaging pipelines18:36 Downstream analysis after molkart19:53 Manual interventions23:27 Minerva25:39 Google Maps for cells27:16 Microscopy community around Nextflow30:34 How to get involved31:38 Changes in Nextflow for microscopy32:43 Nextflow Ambassador program33:17 Conclusion

Womb Wisdom
163. Hormone metabolite testing while TTC

Womb Wisdom

Play Episode Listen Later Feb 12, 2025 44:48


In this week's episode I sit down for a chat with founder + CEO of Oova, Amy D. Oova: Website - https://www.oova.life/ Connect with Amy: IG - https://www.instagram.com/amydivaraniya/ Connect with Holly: IG - ⁠https://www.instagram.com/rosebud_wellness/⁠⁠ Fertility Planning Session - ⁠⁠https://api.leadconnectorhq.com/widget/booking/rCGISOFO5MiA7y6Vakv8⁠

The Incubator
#224 - [Journal Club Shorts] -

The Incubator

Play Episode Listen Later Jul 7, 2024 3:14


Send us a Text Message.Phototherapy Alters the Plasma Metabolite Profile in Infants Born Preterm with Hyperbilirubinemia.Satrom KM, Wang J, Lock EF, Snook K, Lund TC, Rao RB.J Pediatr. 2024 Jun 28:114175. doi: 10.1016/j.jpeds.2024.114175. Online ahead of print.PMID: 38945444As always, feel free to send us questions, comments, or suggestions to our email: nicupodcast@gmail.com. You can also contact the show through Instagram or Twitter, @nicupodcast. Or contact Ben and Daphna directly via their Twitter profiles: @drnicu and @doctordaphnamd. The papers discussed in today's episode are listed and timestamped on the webpage linked below. Enjoy!

Fit Body, Happy Joints
#172: Your nervous system & fitness part 1: Central nervous system fatigue

Fit Body, Happy Joints

Play Episode Listen Later Jun 27, 2024 21:27


The next three episodes will be about specific mechanisms of your nervous system. Today, Dr. Shannon talks about how central nervous system fatigue influences your workouts and how to manipulate variables to reduce central nervous system fatigue. 0:00: Introduction 2:38: The central nervous system's (CNS) role in fatigue4:40: 7 mechanisms that can cause CNS fatigue4:45: 1st mechanism: Metabolite build up6:44: 2nd mechanism: Lack of muscle glycogen or blood glucose 7:24: 3rd mechanism: Pain8:11: 4th mechanism: Post workout inflammatory response 8:53: 5th mechanism: Cardiovascular strain9:29: 6th mechanism: Complex exercises10:10: 7th mechanism: Choosing exercises that you don't enjoy 12:40: Exercise selection and muscle growth 15:30: How to minimize CNS fatigue to get the most out of your workouts14-day free Evlo trialFollow Dr. Shannon on InstagramFollow Fit Body, Happy Joints on Instagram

Neil Rogers Show
Neil Rogers Show (May 26, 1999)

Neil Rogers Show

Play Episode Listen Later Jun 12, 2024 161:43


Real Science Exchange
Future Directions in Choline Symposium Part Two

Real Science Exchange

Play Episode Listen Later Dec 5, 2023 91:39


Today's episode was filmed at the Future Directions in Choline Symposium put on by the University of North Carolina Nutrition Research Institute.Our day two episode opens with Dr. Eric Ciappio and Dr. Jonathan Bortz of Balchem, summarizing day one's focus on pregnancy and early life and previewing day two's focus on the latest choline research targeting adult nutrition. (1:03)The next guest on our roster is Dr. Mark Manary, a professor of pediatrics at the Washington University School of Medicine. Mark's symposium talk discusses choline and food aid. Food aid products are specially designed to address needs from crisis situations. These specialized food aid products are standardized to meet great deficiency or inadequacy needs. On the most extreme side, there is a product called ready-to-eat therapeutic food for children who are starving to death. Other food aid products include those for severely underweight children. Dr. Manary's research consists of clinical trials in sub-Saharan Africa that include different nutrients in food aid to see if there are improvements in children's responses. One trial with the inclusion of DHA found a 6-15 IQ point difference by adding fish oil or DHA. Mark hypothesizes that a doubling of that effect will be observed when choline is added. (6:42)Dr. Rima Obeid from Saarland University Hospital in Homburg, Germany, joins us next. Her symposium presentation focused on choline and pregnancy outcomes. Their research group has found that low or insufficient amounts of choline in the mother's diet during pregnancy are associated with a higher risk for serious birth defects in babies and that the liver health of the infants is also negatively affected by low choline intake of the mother during pregnancy. Rima's future research includes investigating the impacts and interactions of folate and choline consumption during pregnancy on neural tube defects such as spina bifida. In another study, she will focus on the relationship between the severity of congenital heart defects compared to neural tube defects. In particular, they wish to look at the association with low choline in the blood of the children, the mother and the father, because a pilot study suggests a family pattern, which could be due to some genetic background. (17:18)Our next guest is Dr. Susan Smith, Deputy Director of the University of North Carolina Nutrition Research Institute. One of her presentations centered on choline genetics and cognition. Her research has found genetic variation in choline uptake from the diet. One research question was, “Are there choline variants that affect how powerful that choline is in treating a disease condition?” In particular, Dr. Smith was investigating if choline could be used to treat children who have brain damage from prenatal alcohol exposure, and the answer is yes, it's very helpful. Then, they evaluated if some children benefit more than others and found that there is a gene variant that affects how efficiently choline is absorbed from the diet. Children with the variant that reduced choline uptake benefitted the most from supplemental choline. In addition, there was an impact of the gene variant on cognitive function regardless of prenatal alcohol exposure. Children who carried one or two copies of this particular variant had reduced cognitive performance as compared to those children who were lucky enough to be born with the other variant. While we still don't have a blanket recommendation for how much choline pregnant women should consume, Dr. Smith's message to pregnant women is that eating enough choline lets your baby achieve its full potential. (23:32)Dr. Isis Trujillo-Gonzales and Dr. Evan Paules, both with the University of North Carolina Nutrition Research Institute join us. Isis focuses on choline and brain/eye development, while Evan focuses on choline and metabolic health. Dr. Trujillo-Gonzales's research has found that the neurons in the eye that receive light and connect to the rest of our brain are impacted by choline absorption. Her lab has also investigated the mechanism of action for choline's effect on brain development. The stem cells in the brain that give rise to neurons are very sensitive to choline availability. If a pregnant mom is not consuming enough choline, these cells in the baby's brain are not proliferating adequately. Choline is important in the microRNA that fine-tunes the regulation of this pool of stem cells. Dr. Paules's research is focused on the metabolic symptoms of obesity and the impact of choline on them. For example, giving choline to someone who is deficient can ameliorate the symptoms of fatty liver disease.  One area emerging in his work is the loss of lean mass as people age. It appears that increased loss of lean muscle is observed in people who aren't consuming adequate choline. This suggests that as we age, making sure we have sufficient amounts of choline intake may help prevent the loss of lean muscle tissue. (32:58)Dr. Bryan White with the University of Illinois is our next guest, and his area of interest is the microbiome. In particular, he discusses the role of the microbiome in TMAO production. TMAO (trimethylamine N-oxide) is a metabolite that has been associated with cardiovascular disease. In short, the microbiome produces TMA (trimethylamine), which is converted to TMAO in the liver. Some of the seminal TMAO literature suggests that there is a diet effect on the production of TMAO and that diet changes the microbiome so that more TMAO is produced in the bloodstream. When it comes to microbiome research, there are generally four questions that can be asked about the microbial community: 1) Who's there? 2) How many of them are there? 3) What can they do (given their genetic potential)? and 4) What do they do? The seminal research used 16s ribosome technology to evaluate which microbes were present and their abundance in the microbiome of people consuming omnivorous versus vegetarian diets. It stated that there was a correlation between diet and blood levels of TMAO. Dr. White took the small read archives of that manuscript (the sequencing they did of 16s ribosomes) and got the opposite results of the original paper. (42:25)Our next guest is Dr. Jonathan Bortz with Balchem Corporation, whose presentation was titled, “TMAO and Choline: A Mechanistic Perspective.” In the last several years, there have been concerns about choline advanced by a group of investigators who have claimed that excessive intake of meat, eggs, and other animal-source foods (resulting in choline and/or carnitine upon digestion) generate a substance in the blood called TMAO, trimethylamine oxide. Their hypothesis has been that TMAO has a negative effect on the cardiovascular system and has been associated with a high incidence of cardiovascular disease. However, Dr. Bortz presented multiple examples of how the concerns about choline with respect to TMAO having a causative effect on cardiovascular disease really cannot be supported. In other words, choline does not represent a risk to any users, young or old. (51:42)Dr. Julia Maeve Bonner with Sanofi joins us next to give an overview of her presentation about choline and Alzheimer's disease. In her postdoctoral work at MIT, Dr. Bonner focused on the apolipoprotein E (APOE) gene, which is involved in making a protein that helps carry fat in the bloodstream. Dysfunction in this process is thought to contribute to the development of Alzheimer's. APOE4 is the most highly validated risk factor for Alzheimer's. Dr. Bonner wanted to understand what is happening in APOE4 high risk allele compared to the APOE3 neutral risk allele of this gene in brain cells (astrocytes) in culture. She found that the APOE4 astrocytes accumulated neutral lipids, particularly triacylglycerols, to a much higher degree than APOE3 cells. These lipid droplets is associated with many different dysfunctions in the cell that can be associated with neurodegeneration. If APOE4 cells were grown in a choline-rich media, the lipid imbalance was shifted much closer to the APOE3 cells. Dr. Bonner's group was able to pinpoint that phosphatidylcholine synthesis is the mechanism of action by which choline supplementation had the lipid-shifting effect in APOE4 cells. She has also studied choline supplementation in mice that have Alzheimer's disease genes knocked in where they accumulate the plaques that we see in human brains in Alzheimer's disease. In the background, they also have the human APOE knocked in, which means that they're expressing either APOE3 or APOE4. Again, they saw a protection against the accumulation of some of the Alzheimer's-related damage as well as a lipid shift similar to the brain cell cultures. (1:03:00)To summarize the Future Directions in Choline Symposium, Dr. Dr. Stephen Hursting and Dr. Susan Smith with the University of North Carolina Nutrition Research Institute join us. They give their perspectives on the advancements of the field of choline research and leave us with the take-home message that choline is a critical nutrient for the entire healthspan. (1:22:27)Be sure to subscribe so you don't miss an episode of Real Science Exchange. If you haven't checked out day one from the Future Directions in Choline Symposium, we encourage you to do so. If you want one of our new Real Science Exchange t-shirts, screenshot your rating, review, or subscription, and email a picture to anh.marketing@balchem.com. Include your size and mailing address, and we'll get a shirt in the mail to you.

DMPK Insights
DMPK Insights #2: Pathways to Successful Drug Design – Discovery Metabolite ID

DMPK Insights

Play Episode Listen Later Sep 17, 2023 26:43


In this podcast, Dan Weston, Scientific Leader, Biotransformation at GSK discusses his recent publication on the important role that Metabolite ID plays in drug discovery.The episode addresses the following questions:Why studying biotransformation is an important part of early drug design A strategy to combine in silico tools, high-resolution MS and software-assisted data analysis to optimize data delivery and qualityHow this influences medicinal chemistry and the design–make–test cycleSpeaker:Dan Weston, Ph.D.  - Scientific Leader, Biotransformation at GSKDan gained his Ph.D. in ion-trap mass spectrometry from Nottingham Trent University.  He has held positions at Unilever (environmental fate using LC-MS); Schering-Plough (US) (small-molecule Met-ID for drug discovery); Nottingham Trent University (designing and building novel ion-mobility instrumentation); AstraZeneca (Met-ID for drug development); Waters (demo chemist, utility of ion mobility for small molecule applications); Sygnature (Met-ID Team Leader); and currently at GSK (Scientific Leader; providing cross-portfolio biotransformation support). His research interests include structural elucidation using novel mass spectrometric approaches; complementary analytical techniques such as ion mobility for data rationalization and insights into metabolite structure; in silico approaches for efficient data analysis; ambient ionization and rapid sample screening techniquesReference:Weston, D.J., Dave M., Colizza K. et al., 2022. A discovery biotransformation strategy: combining in silico tools with high-resolution mass spectrometry and software-assisted data analysis for high-throughput metabolism, Xenobiotica, 52(8): 928-942Stay tuned for more podcasts in our Pharmaron DMPK Insights Series!

GesundheitsTippTV: Expertengespräche
#082 Länger leben mit fermentierter Nahrung - Prof.Dr. Gunter Eckert im Expertengespräch

GesundheitsTippTV: Expertengespräche

Play Episode Listen Later Sep 10, 2023 47:01


Wohl jeder sehnt sich nach einem langen, gesunden und glücklichen Leben. In diesem Expertengespräch verdeutlicht der Ernährungswissenschaftler Prof.Dr. Gunter Eckert, warum die Ernährung eine entscheidende Rolle spielt. Er erklärt, warum die in Pflanzen enthaltenen Polyphenole und ihre durch Verdauung aufgespaltenen Moleküle besonders wertvoll sind. Diese sogenannten Metabolite sind auch in fermentierten Nahrungsmitteln und in flüssigen Regulaten enthalten. Wissenschaftliche Studien belegen den Einfluss auf die Langelebigkeit bei Versuchstieren.Hier geht es zu den Regulaten der Firma Dr. Niedermaier (Werbung):https://www.regulat.com/produkt?artikel=rechtsregulat-bio

ReInvent Healthcare
Cortisol Metabolite Testing: Finding the Missing Link in your Hormone Health

ReInvent Healthcare

Play Episode Listen Later May 3, 2023 15:07


In this week's episode of ReInvent Healthcare, we talk about a specific type of test that analyzes metabolites in the body. This test analyzes the levels of metabolites to help evaluate for adrenal dysfunction.    IN THIS EPISODE: The DUTCH (Dried Urine Test for Comprehensive Hormones) Test There are different versions of the DUTCH test with different purposes that can check hormones, the cortisol awakening response, and adrenals, which in turn can find out about thyroid function. Another great thing about this test is it can also test for cortisol metabolites. Cortisol Metabolites Once cortisol is broken down by the liver for excretion, it is converted into cortisol metabolites. Each individual person has a different set of chemistry that may be contributing to their symptoms, fatigue, libido, etc. and looking into cortisol metabolites can go a long way in order to understand their dysfunctions better. Cortisone and Cortisol Cortisol is deactivated to cortisone and vice-versa through different types of enzymes. The ratio of cortisol to cortisone and their metabolites is something to look at to see how the body is excreting and this can show signs of inflammation and give us a better picture of how the adrenals are functioning.   RESOURCES: Read through our FREE Resource Adrenal Guide. Get our FREE Guide to Taking a Detailed Health History that gets you to root causes with ease.  Access Additional Resources for Practitioners ready to improve clinical outcomes through our Nutritional Endocrinology Practitioner Training.   Watch our recorded Thyroid Adrenal Workshop here.  

ReInvent Healthcare
Cortisol Metabolite Testing: Finding the Missing Link in Your Hormone Health

ReInvent Healthcare

Play Episode Listen Later May 3, 2023 15:07 Transcription Available


In this week's episode of ReInvent Healthcare, we talk about a specific type of test that analyzes metabolites in the body. This test analyzes the levels of metabolites to help evaluate for adrenal dysfunction. IN THIS EPISODE:The DUTCH (Dried Urine Test for Comprehensive Hormones) TestThere are different versions of the DUTCH test with different purposes that can check hormones, the cortisol awakening response, and adrenals, which in turn can find out about thyroid function. Another great thing about this test is it can also test for cortisol metabolites. Cortisol MetabolitesOnce cortisol is broken down by the liver for excretion, it is converted into cortisol metabolites. Each individual person has a different set of chemistry that may be contributing to their symptoms, fatigue, libido, etc. and looking into cortisol metabolites can go a long way in order to understand their dysfunctions better.Cortisone and CortisolCortisol is deactivated to cortisone and vice-versa through different types of enzymes. The ratio of cortisol to cortisone and their metabolites is something to look at to see how the body is excreting and this can show signs of inflammation and give us a better picture of how the adrenals are functioning.RESOURCES:Read through our FREE Resource Adrenal Guide.Get our FREE Guide to Taking a Detailed Health History that gets you to root causes with ease. Access Additional Resources for Practitioners ready to improve clinical outcomes through our Nutritional Endocrinology Practitioner Training. Watch our recorded Thyroid Adrenal Workshop here.

PaperPlayer biorxiv neuroscience
Improving magnetic resonance spectroscopy in the brainstem periaqueductal grey using spectral registration

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Mar 29, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.29.534678v1?rss=1 Authors: Sirucek, L., Zoelch, N., Schweinhardt, P. Abstract: Purpose: Functional understanding of the periaqueductal grey (PAG), a physiologically and clinically highly relevant brainstem region, can be advanced using proton magnetic resonance spectroscopy (1H-MRS). However, the PAG's small size and high levels of physiological noise are methodologically challenging. This study aimed to (1) improve 1H-MRS data quality in the PAG using spectral registration for frequency and phase error correction, (2) investigate whether spectral registration is particularly useful in cases of greater head motion and (3) examine two metabolite quantification approaches using literature-based or individual-based water relaxation times. Methods: Spectra were acquired in 33 healthy volunteers (50.1 years, SD=17.19, 18 females) on a 3T Philipps MR system using a point-resolved spectroscopy sequence optimized with very selective saturation pulses (OVERPRESS) and voxel-based flip angle calibration (effective volume of interest size: 8.8x10.2x12.2 mm3). Results: Spectral registration significantly improved signal-to-noise ratios (SNR; p=0.048, median value [interquartile range]: 18.0 [17.00-20.00]) and spectral linewidth (N-acetylaspartate peak: p less than 0.001, 4.3 Hz [3.96-4.85]), as well as metabolite fit (p's less than 0.046) compared to post-processing with minimal frequency alignment using interleaved unsuppressed water peaks. Correlational analyses revealed smaller improvements in SNR in cases of greater head motion (p=0.002) recorded with a markerless motion tracking system. Metabolite concentrations were higher when quantified using individual-based compared to literature-based water relaxation times (p's less than 0.001). Conclusion: This study demonstrates that high-quality 1H-MRS can be acquired in the PAG using spectral registration. This offers new opportunities for future 1H-MRS studies in the PAG and possibly also other clinically relevant brain regions with similar methodological challenges. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
FDX1 regulates cellular protein lipoylation through direct binding to LIAS.

PaperPlayer biorxiv cell biology

Play Episode Listen Later Feb 4, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.03.526472v1?rss=1 Authors: Dreishpoon, M., Bick, N., Petrova, B., Warui, D. M., Cameron, A., Booker, S. J., Kanarek, N., Golub, T., Tsvetkov, P. Abstract: Ferredoxins are a family of iron-sulfur (Fe-S) cluster proteins that serve as essential electron donors in numerous cellular processes that are conserved through evolution. The promiscuous nature of ferredoxins as electron donors enables them to participate in many metabolic processes including steroid, heme, vitamin D and Fe-S cluster biosynthesis in different organisms. However, the unique natural function(s) of each of the two human ferredoxins (FDX1 and FDX2) are still poorly characterized. We recently reported that FDX1 is both a crucial regulator of copper ionophore induced cell death and serves as an upstream regulator of cellular protein lipoylation, a mitochondrial lipid-based post translational modification naturally occurring on four mitochondrial enzymes that are crucial for TCA cycle function. Here we show that FDX1 regulates protein lipoylation by directly binding to the lipoyl synthase (LIAS) enzyme and not through indirect regulation of cellular Fe-S cluster biosynthesis. Metabolite profiling revealed that the predominant cellular metabolic outcome of FDX1 loss-of-function is manifested through the regulation of the four lipoylation-dependent enzymes ultimately resulting in loss of cellular respiration and sensitivity to mild glucose starvation. Transcriptional profiling of cells growing in either normal or low glucose conditions established that FDX1 loss-of-function results in the induction of both compensatory metabolism related genes and the integrated stress response, consistent with our findings that FDX1 loss-of-functions is conditionally lethal. Together, our findings establish that FDX1 directly engages with LIAS, promoting cellular protein lipoylation, a process essential in maintaining cell viability under low glucose conditions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
The dietary polyphenol metabolite protocatechuic acid produces acute and sustained effects on hippocampal electrical activity

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Jan 13, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.12.523723v1?rss=1 Authors: Montero-Atalaya, M., Munoz-Arnaiz, R., Makarova, J., Bartolome, B., Moreno-Arribas, V., Herreras, O. Abstract: Dietary polyphenols and in particular bioavailable metabolites resulting from gut microbiota transformations appear to have beneficial effects in situations of impaired cognition, combatting memory deficits in acute pathological models of neurodegeneration. Modifications to blood flow may underlie the effects of these molecules and although some such metabolites cross the blood-brain barrier, their targets and electrophysiological effects remain unknown. Hence, we explored the systemic and direct effects of protochatechuic acid (PCA) on electrical activity in the hippocampus and cortex of anesthetized female rats, recording evoked and spontaneous high-density field potentials (FPs) to mathematically derive pathway-specific FP generators. We found transient and sustained effects of PCA on evoked activity in the CA1 field, including paradoxical actions on excitatory transmission that depend on the route of administration. Systemic delivery of PCA altered the ongoing activity of some FP generators, albeit with marked inter-animal variation. Interestingly, PCA induced the detachment of infraslow cortico-hippocampal activities over a scale of minutes. These results point to direct actions of polyphenols on cell and network electrical activity, some of which reflect non-specific actions. Thus, dietary-derived polyphenols appear to fulfill neuromodulatory roles, encouraging the search for additional targets to better guide their use in preventing brain pathologies. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
Metabolite T1 relaxation times differ across the adult lifespan

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Jan 8, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.06.522927v1?rss=1 Authors: Murali-Manohar, S., Gudmundson, A. T., Hupfeld, K. E., Zöllner, H. J., Hui, S. C. N., Song, Y., Davies-Jenkins, C. W., Gong, T., Wang, G., Oeltzschner, G., Edden, R. A. E. Abstract: Purpose: To investigate the age-dependence of metabolite T1 relaxation times at 3T in both gray- and white-matter-rich voxels. Methods: This manuscript analyzes publicly available metabolite and metabolite-nulled (single inversion recovery TI = 600 ms) spectra acquired at 3T using PRESS localization. Voxels were placed in posterior cingulate cortex and centrum semiovale in 102 healthy volunteers across 5 decades of life (20s to 60s). All spectra were analyzed in Osprey v2.4.0. To estimate T1 relaxation times for tNAA2.0 and tCr3.0, the ratio of modeled metabolite residual amplitudes in the metabolite-nulled spectrum to the full metabolite signal was calculated using the single inversion recovery signal equation. Correlations between T1 and subject age were evaluated. Results: Spearman correlations revealed that estimated T1 relaxation times of tNAA2.0 (rs = -0.43; p less than 0.001) and tCr3.0 (rs = -0.23; p = 0.021) decreased significantly with age in white-matter-rich CSO, and less steeply (and not significantly) for tNAA2.0 (rs = -0.15; p = 0.136) and tCr3.0 (rs = -0.10; p = 0.319) in gray-matter-rich PCC. Conclusion: The analysis harnessed a large publicly available cross-sectional dataset to test an important hypothesis, that metabolite T1 relaxation times change with age. This preliminary study stresses the importance of further work to measure age-normed metabolite T1 relaxation times for accurate quantification of metabolite levels in studies of aging. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
A metabolite sensor subunit of the Atg1/ULK complex regulates selective autophagy

PaperPlayer biorxiv cell biology

Play Episode Listen Later Dec 14, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.13.520293v1?rss=1 Authors: Gross, A., Ghillebert, R., Schuetter, M., Reinartz, E., Rowland, A., Graef, M. Abstract: Cells convert complex metabolic information into stress-adapted autophagy responses. Canonically, multilayered protein kinase networks converge on the conserved Atg1/ULK kinase complex (AKC) to induce non-selective and selective forms of autophagy in response to metabolic changes. Here, we show that, upon phosphate starvation, the metabolite sensor Pho81 interacts with the adaptor subunit Atg11 at the AKC via an Atg11/FIP200 interaction motif to modulate pexophagy by virtue of its conserved phospho-metabolite sensing SPX domain. Notably, we find core AKC components Atg13 and Atg17 are dispensable for phosphate starvation-induced autophagy revealing significant compositional and functional plasticity of the AKC. Our data indicate that, instead of functioning as a selective autophagy receptor, Pho81 compensates for partially inactive Atg13 during pexophagy when TORC1 remains active under phosphate starvation. Our work shows Atg11/FIP200 adaptor subunits not only bind selective autophagy receptors but also modulator subunits that convey metabolic information directly to the AKC for autophagy regulation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv neuroscience
Changes in brain metabolite levels across childhood

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Dec 1, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.30.518618v1?rss=1 Authors: Perdue, M. V., DeMayo, M. M., Bell, T., Boudes, E., Bagshawe, M., Harris, A. D., Lebel, C. Abstract: Metabolites play important roles in brain development and their levels change rapidly in in the prenatal period and during infancy. Metabolite levels are thought to stabilize during childhood, but the development of neurochemistry across early-middle childhood remains understudied. We examined the developmental changes of key metabolites (total N- acetylaspartate, tNAA; total choline, tCho; total creatine, tCr; glutamate+glutamine, Glx; and myo-inositol, mI) using short echo-time magnetic resonance spectroscopy (MRS) in the anterior cingulate cortex (ACC) and the left temporo-parietal cortex (LTP) using a mixed cross- sectional/longitudinal design in children aged 2-11 years (ACC: N=101 children, 112 observations; LTP: N=95 children, 318 observations). We found age-related effects for all metabolites. tNAA increased with age in both regions, while tCho decreased with age in both regions. tCr increased with age in the LTP only, and mI decreased with age in the ACC only. Glx did not show linear age effects in either region, but a follow-up analysis in only participants with greater than or equal to 3 datapoints in the LTP revealed a quadratic effect of age following an inverted U-shape. These substantial changes in neurochemistry throughout childhood likely underlie various processes of structural and functional brain development. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

PaperPlayer biorxiv cell biology
Golgi-IP, a novel tool for multimodal analysis of Golgi molecular content

PaperPlayer biorxiv cell biology

Play Episode Listen Later Nov 23, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.22.517583v1?rss=1 Authors: Fasimoye, R., Dong, W., Nirujogi, R. S., Rawat, E. S., Iguchi, M., Nyame, K., Phung, T. K., Bagnoli, E., Prescott, A. R., Alessi, D. R., Abu-remaileh, M. Abstract: The Golgi is a membrane-bound organelle that is essential for protein and lipid biosynthesis. It represents a central trafficking hub that sorts proteins and lipids to various destinations or for secretion from the cell. The Golgi has emerged as a docking platform for cellular signalling pathways including LRRK2 kinase whose deregulation leads to Parkinson disease. Golgi dysfunction is associated with a broad spectrum of diseases including cancer, neurodegeneration, and cardiovascular diseases. To allow the study of the Golgi at high resolution, we report a rapid immunoprecipitation technique (Golgi-IP) to isolate intact Golgi mini-stacks for subsequent analysis of their content. By fusing the Golgi resident protein TMEM115 to three tandem HA epitopes (GolgiTAG), we purified the Golgi using Golgi-IP with minimal contamination from other compartments. We then established an analysis pipeline using liquid chromatography coupled with mass spectrometry to characterize the human Golgi proteome, metabolome and lipidome. Subcellular proteomics confirmed known Golgi proteins and identified novel ones. Metabolite profiling established the first known human Golgi metabolome and revealed the selective enrichment of uridine-diphosphate (UDP) sugars and their derivatives, which is consistent with their roles in protein and lipid glycosylation. Furthermore, targeted metabolomics validated SLC35A2 as the subcellular transporter for UDP-hexose. Finally, lipidomics analysis showed that phospholipids including phosphatidylcholine, phosphatidylinositol and phosphatidylserine are the most abundant Golgi lipids and that glycosphingolipids are enriched in this compartment. Altogether, our work establishes a comprehensive molecular map of the human Golgi and provides a powerful method to study the Golgi with high precision in health and disease states. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

The Other Side of Weight Loss
Urine Metabolite Testing for Hormones & What it Tells You, Who It is for & Why It is The Gold Standard of Testing with Karen Martel & Cohost Dr. Amie Hornaman

The Other Side of Weight Loss

Play Episode Listen Later Oct 22, 2022 77:38


In this episode, my cohost Dr. Amie Hornaman and I go through her urine hormone metabolite test results. Whether you are a practitioner or lay person this show will teach you in great detail exactly what the urine metabolite hormone test can show you about your hormonal profile. You will learn what is the difference between urine, blood and saliva hormone testing what each marker can tell you in a urine test about your hormone levels and how you break them down what urine testing can tell you about your metabolism and thyroid function the different nuances between urine and serum and why they may not add up what urine testing can tell you about your ability to detoxify and which pathway may be holding you up what markers can show us that we may have an increased risk of developing osteoporosis, breast cancer, acne and more what it means to be an alpha hormone metabolizer versus a beta who the urine test is best for how it can help you personalize your hormone replacement therapy to get the most out of it Amie's blood labs compared with the DUTCH test and the discrepancies it showed the cheapest option you have when buying a urine metabolite test and more!! Watch the video of this episode here.  Check out Dr. Amie Hornaman and her shop here and get 10% off your order with coupon code karen Get $20 off your advanced urine metabolite test with coupon code karen20. The coupon expires on Oct 31st.  Do you have a question for our next Q&A? Please fill out this form. Get the details and apply to be part of my 3-month Mastering Peri & Post Menopause coaching program. Start your membership to the OnTrack group coaching program to help you balance your hormones and lose weight.   Karen Martel, Certified Hormone Specialist & Transformational Nutrition Coach and weight loss expert.  Visit https://karenmartel.com/  Karen's Facebook Karen's Instagram  *I have teamed up with businesses and products that I love and may receive compensation for products I review on this site at no additional cost to you.  

PaperPlayer biorxiv cell biology
Metabolite profiling and cytotoxic activity of Andean potatoes: polyamines and glycoalkaloids as potential anticancer agents in human neuroblastoma cells in vitro

PaperPlayer biorxiv cell biology

Play Episode Listen Later Oct 14, 2022


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.13.512083v1?rss=1 Authors: Lanteri, M. L., Silveyra, M. X., Moran, M. M., Boutet, S., Solis-Gozar, D.-D., Perreau, F., Andreu, A. B. Abstract: Andean potatoes (Solanum tuberosum L. ssp. andigena) are a good source of dietary antioxidant polyphenols. We have previously demonstrated that polyphenol extracts from Andean potato tubers exerted a dose-dependent cytotoxic effect in human neuroblastoma SH-SY5Y cells, being skin extracts more potent than flesh ones. In order to gain insight into the bioactivities of potato phenolics, we investigated the composition and the in vitro cytotoxic activity of total extracts and fractions of skin and flesh tubers of three Andean potato cultivars (Santa Maria, Waicha, and Moradita). Potato total extracts were subjected to liquid-liquid fractionation using ethyl acetate solvent in organic and aqueous fractions. We analyzed both fractions by HPLC-DAD, HPLC-ESI-MS/MS, and HPLC-HRMS. Results corroborated the expected composition of each fraction. Organic fractions were rich in hydroxycinnamic acids (principally chlorogenic acid isomers), whereas aqueous fractions contained mainly polyamines conjugated with phenolic acids, glycoalkaloids, and flavonoids. Organic fractions were not cytotoxic against SH-SY5Y cells, and indeed, some increased cellular metabolism compared to controls. Aqueous fractions were cytotoxic and even more potent than their respective total extracts. Treatment with a combination of both fractions showed a similar cytotoxic response to the corresponding extract. According to correlation studies, it is tempting to speculate that polyamines and glycoalkaloids are crucial in inducing cell death. Our findings indicate that the activity of Andean potato extracts is a combination of various compounds and contribute to the revalorization of potato as a functional food. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

The Gary Null Show
The Gary Null Show - 09.22.22

The Gary Null Show

Play Episode Listen Later Sep 22, 2022 56:42


VIDEOS: The elite that has taken almost all the money is now after everything else as well | Neil Oliver The Metaverse Is Worse Than You Thought – by MOON 11 reasons an annual COVID-19 booster is NOT LIKE an annual flu shot Blackcurrant nectar shows exercise benefits for college students: Study University of the Incarnate Word, September 14, 2022 Daily consumption of blackcurrant nectar for eight days may reduce muscle damage and inflammation after exercise, according to a new study from scientists at the University of the Incarnate Word in San Antonio, Texas. Sixteen ounces per day of the blackcurrant nectar were associated with reductions in the activity of creatine kinase, a blood marker of muscle damage, by 6.7%, compared to 82% increases in activity in the placebo group 48 hours after exercise, report the researchers in the Journal of Dietary Supplements . Researchers led by Alexander Hutchison, PhD, also report that levels of the inflammatory compound interleukin-6 decreased after exercise in participants in the blackcurrant group, compared with increases seen in the placebo group. “In partial support of our primary hypotheses, we found that consumption of black currant nectar for four days before and three days after a bout of eccentric leg exercise significantly reduced circulating markers of muscle damage while maintaining circulating antioxidant capacity,” they wrote in their paper. “Although pain scores in the blackcurrant nectar group returned to baseline a day earlier than the placebo group, there were no significant differences observed between groups at any time point after exercise. The study included 16 college students randomly assigned to consumer either the blackcurrant nectar beverage (CurrantC provided by CropPharms from Staatsburg, NY) or placebo twice a day for eight days. On day 4 the participants performed a bout of knee extension exercises, and blood samples taken 24, 48, and 96 hours after the exercise. Results showed that ORAC levels in the blood significantly decreased in the placebo group, while no significant decreases from the baseline values were observed in the blackcurrant group. In addition, significant differences between the groups were observed for IL-6 levels 24 hours after exercise, while significant differences were observed in creatine kinase activity between the groups after 48 and 96 hours.. How does what we eat affect our health span and longevity? It's a complex, dynamic system Columbia University's Mailman School of Public Health, September 21, 2022 How does what we eat affect how we age? The answer to this relatively concise question is unavoidably complex, according to a new study at the Butler Columbia Aging Center at Columbia University Mailman School of Public Health. The findings are published online in the journal BMC Biology. While most analyses had been concerned with the effects of a single nutrient on a single outcome, a conventional, unidimensional approach to understanding the effects of diet on health and aging no longer provides us with the full picture: A healthy diet must be considered based on the balance of ensembles of nutrients, rather than by optimizing a series of nutrients one at a time. Until now little was known about how normal variation in dietary patterns in humans affects the aging process. “”This study therefore provides further support to the importance of looking beyond ‘a single nutrient at a time' as the one size fits all response to the age-old question of how to live a long and healthy life.” Cohen also points that the results are also concordant with numerous studies highlighting the need for increased protein intake in older people, in particular, to offset sarcopenia and decreased physical performance associated with aging. The researchers analyzed data from 1,560 older men and women, aged 67-84 years selected randomly from the Montreal, Laval, or Sherbrooke areas in Quebec, Canada, who were re-examined annually for three years and followed over four years to assess on a large scale how nutrient intake associates with the aging process. Aging and age-related loss of homeostasis (physiological dysregulation) were quantified via the integration of blood biomarkers. The effects of diet used the geometric framework for nutrition, applied to macronutrients and 19 micronutrients/nutrient subclasses. Researchers fitted a series of eight models exploring different nutritional predictors and adjusted for income, education level, age, physical activity, number of comorbidities, sex, and current smoking status. Four broad patterns were observed: The optimal level of nutrient intake was dependent on the aging metric used. Elevated protein intake improved/depressed some aging parameters, whereas elevated carbohydrate levels improved/depressed others; There were cases where intermediate levels of nutrients performed well for many outcomes (i.e. arguing against a simple more/less is better perspective); There is broad tolerance for nutrient intake patterns that don't deviate too much from norms (“homeostatic plateaus”). Optimal levels of one nutrient often depend on levels of another (e.g. vitamin E and vitamin C). Simpler analytical approaches are insufficient to capture such associations. Mediterranean diet could play a key role in preventing cognitive decline Brigham and Women's Hospital and Harvard University, September 20, 2022 Individuals of minoritized ethnic or racial groups are often underrepresented in research, thus hindering the understanding of risk factors and the efficacy of treatments for diseases in these minoritized groups. A recent study published in the journal Alzheimer's & Dementia found that the levels of six plasma metabolites were associated with lower cognitive function across all racial/ethnic groups, and the levels of most of these blood metabolites were associated with adherence to a Mediterranean diet. Speaking to Medical News Today, the study's corresponding author Dr. Tamar Sofer, a professor at Brigham and Women's Hospital at Harvard University, said: “We identified a few metabolites (small molecules) in blood that their levels are correlated with cognitive function, and they are all related to diet. Characterizing metabolites associated with cognitive function can help researchers understand the mechanisms underlying the development of dementia. Moreover, blood metabolites can be easily measured and could serve as biomarkers for cognitive function. A previous study involving older Puerto Rican individuals showed that the levels of 13 blood metabolites were associated with global cognitive function, which is a composite measure of multiple cognitive abilities. Metabolite levels are influenced by the interplay between genetics, health status, and environmental factors, including diet, other lifestyle factors, and socioeconomic factors, which may differ among and even within ethnic/racial groups. The meta-analysis showed that six blood metabolites were associated with lower cognitive function across all ethnic/racial groups. Four out of the six metabolites associated with overall cognitive function were sugars, including glucose, ribitol, mannose, and mannitol/sorbitol. Out of the six metabolites, the analysis revealed a potential causal effect of only ribitol on cognitive function. The researchers also assessed the association between dietary habits, including adherence to a Mediterranean diet and intake of food groups (i.e. intake of legumes, fruits, vegetables, meat, fish, etc.), and blood metabolite levels. They found that adhering to a Mediterranean diet or its component food groups was correlated with several blood metabolites assessed in the study. Notably, the strongest association was observed between beta-cryptoxanthin and fruit intake participants. Beta-cryptoxanthin is a carotenoid with antioxidant properties found in fruits and vegetables, and beta-cryptoxanthin levels are associated with a lower risk of insulin resistance and liver dysfunction. “[T]his study is a step in the right direction in relation to examining the role of diet and the body's metabolism for brain health. It provides suggestive evidence that adherence to a good diet such as the Mediterranean style diet may be beneficial for brain health over a wide age range.” Indigo Rose Tomatoes Contain An Antioxidant That Fights Diabetes, Cancer and Neurodegenerative Diseases Oregon State University, September 15, 2022 Not only do dark tomatoes turn heads, but they are also healthier than normal red varieties, according to plant scientists. Indigo Rose Tomatoes were cultivated by breeding red and purple tomato plants, and are being heralded as a new superfood with potent antioxidants. Scientists bred purple tomatoes containing anthocyanin, an antioxidant said to help fight several diseases, with normal red varieties. ‘There are some dark coloured tomatoes but Indigo Rose is the only real black tomato and is the darkest that has ever been bred. “It's not genetically modified or GMO-based as many assume,” said Botanist Marjorie Varga. “People often get confused between GMO and hybridization which farmers have been using to cultivate new plant varieties for thousands of years.” “It is the first improved tomato variety in the world that has anthocyanins in its fruit,” he said. Myers' team found some tomatoes with purple pigmentation and tests revealed that anthocyanins were providing the colour, the same as blueberries. They crossed the purple tomatoes with some wild tomatoes and eventually came up with a black strain. Foot massage effective in improving sleep quality and anxiety in postmenopausal women Çankiri Karatekin University (Turkey), September 21, 2022 The therapeutic benefits of massage have long been recognized. A new study suggests that foot massage, in particular, can help minimize a number of common menopause symptoms, including sleep disruption, effectively extending sleep duration by an average of an hour per day. Study results are published online today in Menopause. During the menopause transition, estrogen deficiency can lead to a number of physical and mental health problems, including insomnia, hot flashes, vaginal dryness, headaches and anxiety. Although hot flashes and negative moods commonly seen in in the menopause transition often improve, conditions such as sleep complaints and vaginal dryness tend to persist or worsen over time. Previous studies have suggested that foot reflexology is an effective intervention in reducing stress and fatigue in premenopausal women. However, no previous studies were found that evaluated the effects of foot massage on anxiety, fatigue and sleep at the same time in postmenopausal women. In this new, small-scale study, researchers specifically sought to evaluate the effects of foot massage on anxiety, fatigue and sleep in postmenopausal women. Study results determined that foot massage applied during menopause increases the average daily sleep duration—as much as an hour per day—and reduces women's fatigue and anxiety levels. “Sleep disturbances, fatigue and anxiety symptoms are common during menopause. This small study in Turkish women shows how a simple, inexpensive intervention such as foot massage can improve these bothersome symptoms in postmenopausal women. Lack of sleep negatively impacts immune stem cells, increasing risk of inflammatory disorders and heart disease Icahn School of Medicine at Mount Sinai, September 21, 2022 Chronic insufficient sleep can negatively affect immune cells, which may lead to inflammatory disorders and cardiovascular disease, according to a new study from the Icahn School of Medicine at Mount Sinai. More specifically, consistently losing an hour and a half of sleep a night potentially increases the risk. The research, published in the Journal of Experimental Medicine, is the first to show that sleep alters the structure of DNA inside the immune stem cells that produce white blood cells—also known as immune cells—and this can have a long-lasting impact on inflammation and contribute to inflammatory diseases. Immune cells fight infection, but if the number of these cells gets too high, they overreact and cause inflammation. The study is also the first to show that catching up on sleep doesn't reverse the effects of sleep disruption. “This study begins to identify the biological mechanisms that link sleep and immunological health over the long-term. It shows that in humans and mice, disrupted sleep has a profound influence on the programming of immune cells and rate of their production, causing them to lose their protective effects and actually make infections worse—and these changes are long-lasting. This is important because it is yet another key observation that sleep reduces inflammation and, conversely, that sleep interruption increases inflammation,” says lead author Filip Swirski, Ph.D., Director of the Cardiovascular Research Institute at Icahn Mount Sinai. “This work emphasizes the importance of adults consistently sleeping seven to eight hours a day to help prevent inflammation and disease, especially for those with underlying medical conditions.” A team of investigators analyzed 14 healthy adults who regularly sleep eight hours a night. First, researchers monitored them sleeping at least eight hours a night for six weeks. They drew their blood and analyzed their immune cells. Then, the same group of adults reduced their sleep time by 90 minutes every night for six weeks, and had their blood and immune cells reanalyzed. At the end of the study researchers compared the blood and cell samples from the full night's sleep and restricted sleep periods. All participants had significant changes in their immune cells (also known as hematopoietic cells) due to a lack of sleep—there were more of them, and the DNA structure was altered. After six weeks of sleep restriction, they had an increased number of immune cells. Results in humans showed that fragmented sleep had significant changes to their immune stem cells, producing an increased number of immune cells, and also showed evidence of rewiring and reprogramming. A notable finding from the mouse group was that even after sleep recovery, the immune stem cells retained this rewiring structure, and they continued to produce additional white blood cells, making the mice susceptible to inflammation and disease. “Our findings suggest that sleep recovery is not able to fully reverse the effects of poor-quality sleep. We can detect a molecular imprint of insufficient sleep in immune stem cells, even after weeks of recovery sleep. This molecular imprint can cause the cells to respond in inappropriate ways leading to inflammation and disease,” says co-lead investigator Cameron McAlpine, Ph.D., Assistant Professor of Medicine (Cardiology) at Icahn Mount Sinai.

The People's Scientist
An Exercise Metabolite That Can Reduce Food Intake and Induce Fat Loss

The People's Scientist

Play Episode Listen Later Jul 24, 2022 31:35


In Episode 130 I dive into a recent publication by Li et al. published this year in Nature that identified an exercise metabolite, lac-phe, that reduces food intake and induces fat loss. The scientists conducted a series of experiments to illustrate that certain types of exercise increase circulating lac-phe in the blood which is likely the mechanism behind reduced appetite, food intake, and enhanced fat loss. Tune in for details!Reference: Li, V.L., He, Y., Contrepois, K. et al. An exercise-inducible metabolite that suppresses feeding and obesity. Nature 606, 785–790 (2022). https://doi.org/10.1038/s41586-022-04828-5Want to buy me a coffee to help support the show? You can do so via the links below:Venmo ID: Steph-CalPatreon: https://www.patreon.com/join/DrSCaligiuriBuy Me a Coffee: https://www.buymeacoffee.com/drscaligiuriFollow me on social media to see the papers I cite in this week's episode:IG: Dr.SCaligiuriFB: ThePeoplesScientistTwitter: DrSCaligiuriLinkedin: Stephanie CaligiuriTikTok: Dr.SCaligiuri See acast.com/privacy for privacy and opt-out information.

The Metabolomist podcast
The Metabolomist - Metabolomics2022 Feature

The Metabolomist podcast

Play Episode Listen Later Jul 5, 2022 33:22


This episode features exclusive interviews collected at the 2022 Metabolomics Society conference in Valencia, Spain.

The Revive Stronger Podcast
306: Should You Do Banded Exercises w/ Mike Israetel & Kassem Hanson

The Revive Stronger Podcast

Play Episode Listen Later Apr 11, 2022 98:18


Mike & Kassem are back on the show together to talk more about biomechanics. In today's show, we dig into the utility of bands for adjusting resistance profiles, specifically for exercises like the hack squat. As always guys lots of detail and nuance to be found in this chat along with some practical take-homes. Timestamps: (00:00) Intro (01:55) Is banding worth it? Banding on hack squats (20:04) How to quantify the benefits of banding (28:56) Sticking point on a hack squat & rationale to band the hack squats (43:04) Argument for banding exercises and how to do it (51:01) Stimulus to fatigue ratio when banding (01:01:45) Time consumption (01:09:14) Making movements easier/harder (01:14:55) Metabolite work and defeating the purpose of banding (01:22:56) Conclusion https://www.instagram.com/coach_kassem/ https://www.instagram.com/N1.education/ https://www.instagram.com/drmikeisraetel/ https://www.instagram.com/rpstrength/ Thanks, please comment, like and subscribe! COACHING: https://revivestronger.com/online-coaching/ MEMBERSITE: https://revivestronger.com/team-revive-stronger/ WEBSITE: https://www.revivestronger.com FACEBOOK: http://www.facebook.com/revivestronger INSTAGRAM: http://www.instagram.com/revivestronger NEWSLETTER: https://bit.ly/2rRONG5 YOUTUBE: https://www.youtube.com/watch?v=fluVEKr2UV0 __________________________________________________________________ If you want to support us via a donation, that's highly appreciated! Patreon • https://www.patreon.com/revivestronger Don't like Patreon, go to Paypal! • https://bit.ly/2XZloJ4 __________________________________________________________________ Our Ebooks! Ultimate Guide To Contest Prep Ebook: • https://revivestronger.com/product/the-ultimate-guide-to-contest-prep/ Primer Phase Ebook: • https://revivestronger.com/product/the-primer-phase/ __________________________________________________________________ Stay up to date with the latest research and educate yourself! MASS (Research Review): • https://goo.gl/c7FSJD RP+ Membership: • https://ob262.isrefer.com/go/plus/Steve90/ JPS Mentorship • https://jpseducation.mykajabi.com/a/13324/esJ8AZwy __________________________________________________________________ Books we recommend! Muscle & Strength Pyramids • https://goo.gl/S8s6tG RP Books • http://bit.ly/2vREaH0 RP + Members site • https://ob262.isrefer.com/go/plus/Steve90/ For more • http://revivestronger.com/library/ __________________________________________________________________ Supplements: www.cnpprofessional.co.uk - STEVE15 for 15% off __________________________________________________________________ When you're interested in online coaching, please go visit our website and follow the application form: https://www.revivestronger.com/online-coaching/

The Revive Stronger Podcast
297: Brad Schoenfeld - How To Periodise For Max Muscle Growth

The Revive Stronger Podcast

Play Episode Listen Later Feb 7, 2022 59:00


Brad is back on the show for his annual appearance. In this episode, we dig into the question of whether you should cut volume to preserve muscle in a cut if partial repetitions can be beneficial for hypertrophy, and questions surrounding the periodised programme within his recent book release. Timestamps: (00:00) Intro (06:01) Differences between Max Muscle Plan version 1 & 2. Nutrient timing (10:48) What's a true evidence-based practitioner (12:30) Who is the book for? (16:30) Volume and preserving muscle mass (22:11) Full ROM vs. Partial ROM (31:16) Is variation important for hypertrophy? (35:26) How to periodise for max muscle growth (39:56) Metabolite training for hypertrophy (42:37) Combine all things at once? (44:30) Is failure necessary when you train with higher reps? (45:43) Importance of exercise order (51:00) Specialisation phases necessary with training experience and what's junk volume https://www.instagram.com/bradschoenfeldphd/ https://www.amazon.com/M-X-Muscle-Plan-2-0/dp/171820714X/ http://www.lookgreatnaked.com/about_brad.php Thanks, please comment, like and subscribe! COACHING: https://revivestronger.com/online-coaching/ MEMBERSITE: https://revivestronger.com/team-revive-stronger/ WEBSITE: https://www.revivestronger.com MINI CUT MOVEMENT: https://revivestronger.com/mini-cut-movement/ FACEBOOK: http://www.facebook.com/revivestronger INSTAGRAM: http://www.instagram.com/revivestronger NEWSLETTER: https://bit.ly/2rRONG5 YOUTUBE: https://www.youtube.com/watch?v=J0sikTfehbk __________________________________________________________________ If you want to support us via a donation, that's highly appreciated! Patreon • https://www.patreon.com/revivestronger Don't like Patreon, go to Paypal! • https://bit.ly/2XZloJ4 __________________________________________________________________ Our Ebooks! Ultimate Guide To Contest Prep Ebook: • https://revivestronger.com/product/the-ultimate-guide-to-contest-prep/ Primer Phase Ebook: • https://revivestronger.com/product/the-primer-phase/ __________________________________________________________________ Stay up to date with the latest research and educate yourself! MASS (Research Review): • https://goo.gl/c7FSJD RP+ Membership: • https://ob262.isrefer.com/go/plus/Steve90/ JPS Mentorship • https://jpseducation.mykajabi.com/a/13324/esJ8AZwy __________________________________________________________________ Books we recommend! Muscle & Strength Pyramids • https://goo.gl/S8s6tG RP Books • http://bit.ly/2vREaH0 RP + Members site • https://ob262.isrefer.com/go/plus/Steve90/ For more • http://revivestronger.com/library/ __________________________________________________________________ __________________________________________________________________ When you're interested in online coaching, please go visit our website and follow the application form: https://www.revivestronger.com/online-coaching/

RP Strength Podcast
RP Coach Hunter Pauley

RP Strength Podcast

Play Episode Listen Later Jan 24, 2022 61:08


0:28 How Hunter became an RP coach 3:30 Hunter adapting to Montana life and weather 11:15 Hunter's struggles in highschool 15:45 Hunter's introduction to fitness 19:55 Hunter's education 24:34 How Hunter found RP 29:26 Managing lifting volume 33:45 Metabolite training 40:00 Montana hiking 42:45 Hunters coaching success stories 48:00 Meal prep and diet tips 52:12 What Hunter gives to his clients 58:58 How to find Hunter

Oncotarget
Microbial Metabolite Mimicry May Improve Drug Discovery

Oncotarget

Play Episode Listen Later Jan 17, 2022 17:23


Dr. Sridhar Mani from Medicine and Genetics of The Albert Einstein College of Medicine, Bronx, NY, details his editorial published by Oncotarget in Volume 11, Issue 19, entitled, “Microbial metabolite mimicry: one step closer to drug discovery.” DOI - https://doi.org/10.18632/oncotarget.27591 Correspondence to - Sridhar Mani - sridhar.mani@einsteinmed.org Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27591 Keywords - microbial metabolites, inflammation, IBD, mimicry, drugs About Oncotarget Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

Lupus Science and Medicine podcast
Personalised metabolite monitoring during pre-conception and pregnancy in SLE patients

Lupus Science and Medicine podcast

Play Episode Listen Later Nov 17, 2021 18:15


Duane Peters from the Lupus Foundation of America interviews Francisca Lambert-Fliszar and Dr Evelyne Vinet from McGill University Health Centre in Canada. They discuss monitoring 6-mercaptopurine (6-MP) metabolite levels to enable personalisation of immunosuppressive therapies prior to conception or during pregnancy, in order to most effectively and safely control the disease during this critical time. Access the paper here: https://lupus.bmj.com/content/8/1/e000519

BacterioFiles
463: Selectively Stimulating Cell Squatters

BacterioFiles

Play Episode Listen Later Sep 20, 2021 12:00


This episode: Bacteria produce a compound that causes a phage lurking in the genome of a competing species to wake up and start killing that competitor! Download Episode (8.2 MB, 12.0 minutes) Show notes: Microbe of the episode: Zaire ebolavirus   News item   Takeaways Some bacteriophages infect and immediately destroy their hosts in a burst of new viruses, while others can be stealthier, integrating their genome into the genome of the host and remaining there quietly even over multiple generations of the bacteria. When something stresses the host, such as DNA damage, these integrated phages (prophages) become active and start producing new viruses, killing their host like the other kind does.   In this study, one kind of bacteria release a chemical that wakes up phages in a competitor species of bacteria. This is helpful for competition, but even more interesting is that out of the six prophages in the competitor species, the chemical wakes up only one of them. Such selective phage induction could be interesting to study.   Journal Paper: Jancheva M, Böttcher T. 2021. A Metabolite of Pseudomonas Triggers Prophage-Selective Lysogenic to Lytic Conversion in Staphylococcus aureus. J Am Chem Soc 143:8344–8351. Other interesting stories: Lab-evolved fungus strain could protect honeybees from mites   Email questions or comments to bacteriofiles at gmail dot com. Thanks for listening! Subscribe: Apple Podcasts, Google Podcasts, Android, or RSS. Support the show at Patreon, or check out the show at Twitter or Facebook.

The Microbiome Report
Everything You Need To Know About Short-Chain Fatty Acids

The Microbiome Report

Play Episode Listen Later Aug 5, 2021 33:38


Typically, we don't think about picking up the waste byproducts of another species and using them to our advantage. But when it comes to short chain fatty acids - the metabolites of byproducts of our microbes - there's actually a lot we humans benefit from. On this episode, Stephen Fleming, president of Traverse Science, talks to Andrea about what short-chain fatty acids are, what they do, what they mean in the body, and where we can find them. Leave Us A Rating And Review! The Microbiome Report is powered by BIOHM Health. Save 15% off at biohmhealth.com with the code POD15.  Find the transcript and show notes for this episode at biohmhealth.com/pages/podcast.  Questions? Ideas? Email us at themicrobiomereport@biohmhealth.com or reach out on Instagram @DreEats or @BIOHMHealth.

The Blood Flow Restriction (BFR) University Podcast
Metabolite Accumulation | Pre-fatiguing Tissue | New Cuffs | BFR Q&A

The Blood Flow Restriction (BFR) University Podcast

Play Episode Listen Later May 20, 2021 22:28


Join Dr. Ed Le Cara as he answers people's questions about BFR. In this session, he talks about metabolite accumulation, why and how you should pre fatigue tissue, what are the effects on the area distal to and proximal to the cuff, and what are the best effects. He also shares how BFR can help with osteoporotic or osteopenia and a lot more. For More: https://www.bfruniversity.com/

Bio Patrika Podcast
Vigyan Patrika S2 EP15: RNA-based biosensors win a race for metabolite-sensing in cells

Bio Patrika Podcast

Play Episode Listen Later Apr 12, 2021 7:10


This episode is also available as a blog post: http://biopatrika.com/2021/04/12/interview-rna-biosensors-metabolite-sensing-cells/

The Revive Stronger Podcast
247: Brad Schoenfeld - Training to failure for strength & hypertrophy

The Revive Stronger Podcast

Play Episode Listen Later Feb 22, 2021 65:43


The hypertrophy king Dr Brad Schoenfeld is back on the show. In this episode we talk about a recent paper whereby a strength phase proceeded a hypertrophy phase & saw more gains, we also discussed Brad's recent meta-analysis on failure training and much more! Timestamps: 00:00 Intro 01:20 Sissy squats 03:46 Strength phases beneficial for hypertrophy? 08:07 Overreaching a good thing? 08:55 People dismissing science 13:52 The arguments of overthinking things 15:59 Training to failure for strength & hypertrophy 26:15 Argument of "You don't know how to train to failure" 29:58 What is the definition of training to failure 32:45 What is too easy of training? 37:08 Detrimental effects of systemic fatigue 43:49 Genetic ceiling 47:27 Max muscle plan, new version and what are differences 51:06 Periodisation and programme 54:46 Metabolite blocks 59:45 Dogmatism and black & white statements https://www.lookgreatnaked.com/ https://www.instagram.com/bradschoenfeldphd/ https://www.facebook.com/brad.schoenfeld.cscs https://twitter.com/BradSchoenfeld Thanks, please comment, like and subscribe! COACHING: https://revivestronger.com/online-coaching/ MEMBERSITE: https://revivestronger.com/team-revive-stronger/ WEBSITE: https://www.revivestronger.com MINI CUT MOVEMENT: https://revivestronger.com/mini-cut-movement/ FACEBOOK: http://www.facebook.com/revivestronger INSTAGRAM: http://www.instagram.com/revivestronger NEWSLETTER: https://bit.ly/2rRONG5 YOUTUBE: https://www.youtube.com/watch?v=XjWbbkgZg2Q __________________________________________________________________ If you want to support us via a donation, that's highly appreciated! Patreon • https://www.patreon.com/revivestronger Don't like Patreon, go to Paypal! • https://bit.ly/2XZloJ4 __________________________________________________________________ Our Ebooks! Ultimate Guide To Contest Prep Ebook: • https://revivestronger.com/product/the-ultimate-guide-to-contest-prep/ Primer Phase Ebook: • https://revivestronger.com/product/the-primer-phase/ __________________________________________________________________ Stay up to date with the latest research and educate yourself! MASS (Research Review): • https://goo.gl/c7FSJD RP+ Membership: • https://ob262.isrefer.com/go/plus/Steve90/ JPS Mentorship • https://jpseducation.mykajabi.com/a/13324/esJ8AZwy __________________________________________________________________ Books we recommend! Muscle & Strength Pyramids • https://goo.gl/S8s6tG RP Books • http://bit.ly/2vREaH0 RP + Members site • https://ob262.isrefer.com/go/plus/Steve90/ For more • http://revivestronger.com/library/ __________________________________________________________________ __________________________________________________________________ When you're interested in online coaching, please go visit our website and follow the application form: https://www.revivestronger.com/online-coaching/

Clinical Chemistry Podcast
The Vitamin D Metabolite Ratio is Independent of Vitamin D Binding Protein Concentration

Clinical Chemistry Podcast

Play Episode Listen Later Jan 31, 2021 12:05


Living Lean
Q+A: Using Metabolite Training, Pushing & Pulling Calories, And More...

Living Lean

Play Episode Listen Later Jan 1, 2021 22:54


Q&A! Today, we're diving into the ins & outs of metabolite training, when you should and shouldn't push or pull calories, and more.Click here now to apply for online coaching with our team.

Swole Radio
12. DR. ERIC HELMS: BODYBUILDING PERIODIZATION - DUP, Length of Massing, Metabolite Training, Macrocycles

Swole Radio

Play Episode Listen Later Nov 29, 2020 72:17


Dr. Eric Helms is a leading strength and hypertrophy expert. We spoke in depth about periodization for bodybuilders: Units of time in the training year DUP (daily undulating periodization) Mesocycle progression Progression across mesocycles: volume, frequency, rep ranges, exercise selection Metabolite blocks Length of massing phases Optimal body fat percentage for muscle growth Rates of gain Resensitization phases Frequency of fat loss phases Where he’s at in his season Find Dr. Helms at: https://3dmusclejourney.com/ IG: @helms3dmj ------------------------------- Follow me on social media: YOUTUBE: www.youtube.com/c/AskDrSwole INSTAGRAM: http://instagram.com/dr_swole FACEBOOK: https://www.facebook.com/bill.wong22/ TIKTOK: https://www.tiktok.com/@dr_swole/ ------------------------------- About me: I'm a medical doctor and natural men’s physique athlete based in Vancouver, Canada. I seek to share science-based perspectives to help people lose fat and gain muscle. These will reflect the current expert consensus in the scientific bodybuilding community. I‘m lifetime drug-free and have been training since 2012. ------------------------------- Disclaimers: Consider seeing a physician to assess your readiness before beginning any fitness program. Information presented here is to be applied intelligently in the individual context. I do not assume liability for any loss incurred by using information in this podcast.

PaperPlayer biorxiv biochemistry
Public LC-Orbitrap-MSMS Spectral Library for Metabolite Identification

PaperPlayer biorxiv biochemistry

Play Episode Listen Later Nov 22, 2020


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.21.392266v1?rss=1 Authors: Phapale, P., Palmer, A., Gathungu, R. M., Kale, D., Brugger, B., Alexandrov, T. Abstract: Liquid chromatography-mass spectrometry(LC-MS)-based untargeted metabolomics studies require high-quality spectral libraries for reliable metabolite identification. We have constructed EMBL-MCF, an open LC-MS/MS spectral library that currently contains over 1600 fragmentation spectra from 435 authentic standards of endogenous metabolites and lipids. The unique features of the library are presence of chromatographic profiles acquired with different LC-MS methods and coverage of different adduct ions. The library covers many biologically important metabolites with some unique metabolites and lipids as compared to other public libraries. The EMBL-MCF spectral library is created and shared using an in-house developed web-application at https://curatr.mcf.embl.de/. The library is freely available online and also integrated with other mass spectral repositories. Copy rights belong to original authors. Visit the link for more info

PaperPlayer biorxiv neuroscience
ZIKA virus effects on neuroprogenitors are exacerbated by the main pyriproxyfen metabolite via thyroid hormone signaling disruption

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Nov 3, 2020


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.03.366468v1?rss=1 Authors: Spirhanzlova, P., Sebillot, A., Vancamp, P., Gothie, J.-D., Le Mevel, S., Leemans, M., Wejaphikul, K., Meima, M., Mughal, B. B., Butruille, L., Roques, P., Remaud, S., Fini, J.-B., Demeneix, B. A. Abstract: North-Eastern Brazil saw intensive application of the insecticide pyriproxyfen (PPF) during the microcephaly outbreak caused by Zika virus (ZIKV). ZIKV requires the neural RNA-binding protein Musashi-1 to replicate. TH represses MSI1. Being a suspected TH disruptor, we hypothesized that co-exposure to the main metabolite of PPF, 4'-OH-PPF, would exacerbate ZIKV effects through increased MSI1 expression. This was tested using in vitro mouse neurospheres and an in vivo TH signaling reporter model, Xenopus laevis. TH signaling was decreased by 4'-OH-PPF in both models. In mouse-derived neurospheres the metabolite reduced neuroprogenitor proliferation as well as markers of neuronal differentiation. The results demonstrated that 4'-OH-PPF significantly induced MSI1 at both the mRNA and protein level, as well as Fasn mRNA. Other TH target genes were also significantly modified. Importantly, several key genes implicated in neuroprogenitor fate and commitment were not dysregulated by 4'-OH-PPF alone, but were in combination with ZIKV infection. These included the neuroprogenitor markers Nestin, Egfr, Gfap, Dlx2 and Dcx. Unexpectedly, 4'-OH-PPF decreased ZIKV replication, although only at the fourth and last day of incubation, and RNA copy numbers stayed within the same order of magnitude. However, intracellular RNA content of neuroprogenitors was significantly decreased in the combined presence of the PPF metabolite and ZIKV. We conclude that 4'-OH-PPF interferes with TH action in vivo and in vitro, inhibiting neuroprogenitor proliferation. In the presence of ZIKV, TH signaling pathways crucial for cortical development are significantly impacted. This provides another example of viral effects that are exacerbated by drug or pesticide use. Copy rights belong to original authors. Visit the link for more info

PaperPlayer biorxiv bioinformatics
Joint automatic metabolite identification and quantification of a set of 1H NMR spectra

PaperPlayer biorxiv bioinformatics

Play Episode Listen Later Oct 9, 2020


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.08.331090v1?rss=1 Authors: Lefort, G., Liaubet, L., Marty-Gasset, N., Canlet, C., Vialaneix, N., Servien, R. Abstract: Metabolomics is a promising approach to characterize phenotypes or to identify biomarkers. It is also easily accessible through NMR, which can provide a comprehensive understanding of the metabolome of any living organisms. However, the analysis of 1H NMR spectrum remains difficult, mainly due to the different problems encountered to perform automatic identification and quantification of metabolites in a reproducible way. In addition, methods that perform automatic identification and quantification of metabolites often do it for one given complex mixture spectrum. Hence, when a set of complex mixture spectra coming from the same experiment has to be processed, the approach is simply repeated independently for every spectrum, despite their resemblance. Here, we present a new method that is the first to identify and quantify metabolites by integrating information coming from several complex spectra of the same experiment. The performances of this new method are then evaluated on both simulated and real datasets. The results show an improvement in the metabolite identification and in the accuracy of metabolite quantifications, especially when the concentration is low. This joint procedure is available in version 2.0 of ASICS package. Copy rights belong to original authors. Visit the link for more info

Total Fitheads
Drunk CrossFit WOD (ft. Bryan Boorstein)

Total Fitheads

Play Episode Listen Later Sep 30, 2020 62:18


Bryan Boorstein is the coach that created Evolved Training Systems and Paragon Training. He's a CrossFit regional athlete, L2 trainer and has coached over 75 athletes to the CrossFit Games. He's evolved from functional fitness to physique and offers hybrid programs that includes strength, Olympic lifting, bodybuilding, gymnastics and more. We talk with him about everything from hormones to metabolite training to macros to reverse pyramid training and more. Also, he did Fran drunk.

The Revive Stronger Podcast
170: The Improvement Season - Were the Bros right all along?

The Revive Stronger Podcast

Play Episode Listen Later Sep 21, 2020 63:45


This time we're talking about whether the bros have been right all along? Timestamps 00:00 Intro 03:45 Pumps 05:56 Metabolite training 10:46 Nutrition for Pascal & Steve 22:08 Sleep and its impact on overall wellbeing 26:22 Struggling with eating more food 33:48 Have the bros been right all along? 47:27 Thinking in a box 49:38 Broish mentality and tribalism 52:01 Staying true to yourself, innovators 56:39 Development of science Thanks, please comment, like and subscribe! COACHING: https://revivestronger.com/online-coaching/ MEMBERSITE: https://revivestronger.com/team-revive-stronger/ WEBSITE: https://www.revivestronger.com MINI CUT MOVEMENT: https://revivestronger.com/mini-cut-movement/ FACEBOOK: http://www.facebook.com/revivestronger INSTAGRAM: http://www.instagram.com/revivestronger NEWSLETTER: https://bit.ly/2rRONG5 YOUTUBE: https://www.youtube.com/watch?v=_SftQwB8CC4 __________________________________________________________________ If you want to support us via a donation, that's highly appreciated! Patreon • https://www.patreon.com/revivestronger Don't like Patreon, go to Paypal! • https://bit.ly/2XZloJ4 __________________________________________________________________ Our Ebooks! Ultimate Guide To Contest Prep Ebook: • https://revivestronger.com/product/the-ultimate-guide-to-contest-prep/ Primer Phase Ebook: • https://revivestronger.com/product/the-primer-phase/ __________________________________________________________________ Stay up to date with the latest research and educate yourself! MASS (Research Review): • https://goo.gl/c7FSJD RP+ Membership: • https://ob262.isrefer.com/go/plus/Steve90/ JPS Mentorship • https://jpseducation.mykajabi.com/a/13324/esJ8AZwy __________________________________________________________________ Books we recommend! Muscle & Strength Pyramids • https://goo.gl/S8s6tG RP Books • http://bit.ly/2vREaH0 RP + Members site • https://ob262.isrefer.com/go/plus/Steve90/ For more • http://revivestronger.com/library/ __________________________________________________________________ __________________________________________________________________ When you're interested in online coaching, please go visit our website and follow the application form: https://www.revivestronger.com/online-coaching/

PaperPlayer biorxiv biochemistry
Modular metabolite assembly in C. elegans lysosome-related organelles

PaperPlayer biorxiv biochemistry

Play Episode Listen Later Aug 24, 2020


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.22.262956v1?rss=1 Authors: Le, H. H., Wrobel, C. J., Cohen, S. M., Yu, J., Park, H., Helf, M. J., Curtis, B. J., Rodrigues, P. R., Sternberg, P. W., Schroeder, F. C. Abstract: Signaling molecules derived from attachment of diverse primary metabolic building blocks to ascarosides play a central role in the life history of C. elegans and other nematodes; however, many aspects of their biogenesis remain unclear. Using comparative metabolomics, we show that lysosome-related organelles (LROs) are required for biosynthesis of most modular ascarosides as well as previously undescribed modular glucosides. Both modular glucosides and ascarosides are derived from highly selective assembly of moieties from nucleoside, amino acid, neurotransmitter, and lipid metabolism. We further show that cholinesterase (cest) homologs that localize to the LROs are required for assembly of both modular ascarosides and glucosides, mediating formation of ester and amide linkages between subsets of building blocks. Their specific biosynthesis suggests that modular glucosides, like ascarosides, serve dedicated signaling functions. Further exploration of LRO function and cest homologs in C. elegans and other animals may reveal additional new compound families and signaling paradigms. Copy rights belong to original authors. Visit the link for more info

PaperPlayer biorxiv biochemistry
The malaria metabolite HMBPP does not trigger erythrocyte terpene production

PaperPlayer biorxiv biochemistry

Play Episode Listen Later Jul 30, 2020


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.29.225839v1?rss=1 Authors: Miller, J., Odom John, A. R. Abstract: Infection with malarial parasites renders hosts more mosquito attractive than their uninfected, healthy, counterparts. One volatile organic compound, -pinene, is associated with Plasmodium spp. infection in multiple studies and is a known mosquito attractant. However, how malarial infection results in elevated levels of host-associated -pinene remains unclear. One study suggests that erythrocyte exposure to the malarial metabolite, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), results in increased levels of -pinene. Here, we establish that endogenous levels of -pinene are present in human erythrocytes, that these levels vary widely by erythrocyte donor, and that -pinene levels are not altered by HMBPP treatment. Copy rights belong to original authors. Visit the link for more info

PaperPlayer biorxiv biochemistry
Development and validation of an HPLC method to quantify 2-Keto-3-deoxy-gluconate (KDG), a major metabolite in pectin and alginate degradation pathways

PaperPlayer biorxiv biochemistry

Play Episode Listen Later Jul 25, 2020


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.24.220400v1?rss=1 Authors: Martis B, S., Droux, M., Deboudard, F., Nasser, W., Meyer, S., Reverchon, S. Abstract: A rapid and sensitive High Performance Liquid Chromatography (HPLC) method with UV and fluorescence detection is developed for routine analysis of 2-Keto-3-deoxy-gluconate (KDG), a catabolite product of pectin and alginate. These polysaccharides are both used for biofuel production and to generate high-value-added products. HPLC is performed, after derivatization of the carbonyl groups of the metabolite with O-phenylenediamine (OPD), using a linear gradient of trifluoroacetic acid and acetonitrile. Quantification is accomplished with an internal standard method. The gradient is optimized to distinguish KDG from its close structural analogues such as 5-keto-4-deoxyuronate (DKI) and 2,5-diketo-3-deoxygluconate (DKII). The proposed method is simple, highly sensitive and accurate for time course analysis of pectin or alginate degradation. Copy rights belong to original authors. Visit the link for more info

Personalized Medicine Podcast
Ep#015: Enabling Personalized Medicine through Biomarkers of Response with Dr. Liz O'Day

Personalized Medicine Podcast

Play Episode Listen Later Jul 1, 2020 53:08


In episode 15, our host Oleksandr Yagensky sat down with Dr. Liz O’Day, the founder and CEO of Olaris, a biotech company that enables patients to pursue most effective personalized treatments. Liz unravels how small molecule metabolites along with machine learning can be utilized to evaluate patient-specific responses to therapeutics. Together with Olaris, Liz is shaping the future of personalized medicine. Just two weeks ago, she was elected to the Board of Directors at Personalized Medicine Coalition in recognition of her contribution to the field.Together with Liz, we discussed: ◦ The startup story of Olaris ◦ Biomarkers of Response (BORs) ◦ The future of biomarker panels and multi-omics ◦ Metabolite based biomarker profiling ◦ Analytical platforms used at Olaris ◦ How Olaris leverages machine-learning to find patient-specific metabolite patterns ◦ Application cases for Olaris technology in cancer treatment ◦ Three part aim of Olaris ◦ Bringing the stakeholders in healthcare together ◦ Role of science in becoming a successful entrepreneur ◦ Common challenges faced by biotech start-ups ◦ The future of personalized medicineGet in touch with Liz: ◦ LinkedIn: @Liz O'Day ◦ Twitter: @Lizzard0126 ◦ Facebook: https://www.facebook.com/olarisBoR/ ◦ Instagram: https://www.instagram.com/lizzard0126/ ◦ Web: https://www.olarisbor.com/Make sure to download the full show notes with our guest's bio, links to their most notable work, and our recommendations for further reads on the topic of the episode at pmedcast.com

Prestasjonsprat
Laktat

Prestasjonsprat

Play Episode Listen Later Jun 24, 2020 48:55


Laktat er noe vi snakker om, måler og forsøker å benytte i daglig treningsarbeid, særlig når det gjelder såkalt terskeltrening.Blant trenere, mosjonister og idrettsutøvere omtales ofte konseptene rundt laktat-terskel og anaerob terskel litt feil, sannsynligvis fordi fysiologien er mer kompleks enn vi klarer å ta innover oss. I tillegg har laktat, eller "melkesyre", har fått et ufortjent dårlig rykte som vi vil til livs! Lær om historien bak laktat og anaerob terskel og om noen av laktat sine viktige og spennende funksjoner i kroppen. Følg oss i sosiale medier på @prestasjonsprat Referanse artikler: Proia, P.; Di Liegro, C.M.; Schiera, G.; Fricano, A.; Di Liegro, I. Lactate as a Metabolite and a Regulator in the Central Nervous System. Int. J. Mol. Sci. 2016, 17, 1450 https://www.mdpi.com/1422-0067/17/9/1450 Barros, L. F. (2013). Metabolic signaling by lactate in the brain. Trends in Neurosciences, 36(7), 396-404https://www.sciencedirect.com/science/article/pii/S0166223613000635 Ferguson, B.S., Rogatzki, M.J., Goodwin, M.L. et al. Lactate metabolism: historical context, prior misinterpretations, and current understanding. Eur J Appl Physiol 118, 691–728 (2018). https://doi.org/10.1007/s00421-017-3795-6 https://dx.doi.org/10.1007/s00421-017-3795-6 See acast.com/privacy for privacy and opt-out information.

PaperPlayer biorxiv neuroscience
NMR Analysis of the Correlation of Metabolic Changes in Blood and Cerebrospinal Fluid in Alzheimer Model Male and Female Mice

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Jun 1, 2020


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.26.116525v1?rss=1 Authors: Stojanovic, F., Taktek, M., Khieu, N. H., Huang, J., Jiang, S., Rennie, K., Chakravarthy, B., Costain, W. J., Cuperlovic-Culf, M. Abstract: The development of effective therapies as well as early, molecular diagnosis of Alzheimers disease is impeded by the lack of understanding of the underlying pathological mechanisms. Metabolomics studies of body fluids as well as brain tissues have shown major changes in metabolic profiles of Alzheimers patients. However, with analysis performed at the late stages of the disease it is not possible to distinguish causes and consequence. The mouse model APP/PS1 expresses a mutant amyloid precursor protein resulting in early Amyloid {beta} (A{beta}) accumulation as well as many resulting physiological changes including changes in metabolic profile and metabolism. Analysis of metabolic profile of cerebrospinal fluid (CSF) and blood of APP/PS1 mouse model can provide information about metabolic changes in these body fluids caused by A{beta} accumulation. Using our novel method for analysis of correlation and mathematical ranking of significant correlations between metabolites in CSF and blood, we have explored changes in metabolite correlation and connectedness in APP/PS1 and wild type mice. Metabolites concentration and correlation changes in CSF, blood and across the blood brain barrier determined in this work are affected by the production of amyloid plaque. Metabolite changes observed in the APP/PS1 mouse model are the response to the mutation causing plaque formation, not the cause for the plaque suggesting that they are less relevant in the context of early treatment and prevention then the metabolic changes observed only in humans. Copy rights belong to original authors. Visit the link for more info

PaperPlayer biorxiv neuroscience
Whole-Brain High-Resolution Metabolite Mapping with 3D Compressed-Sensing-SENSE-LowRank 1H FID-MRSI

PaperPlayer biorxiv neuroscience

Play Episode Listen Later May 20, 2020


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.18.101618v1?rss=1 Authors: Klauser, A., Klauser, P., Grouiller, F., Courvoisier, S., Lazeyras, F. Abstract: There is a growing interest of the neuroscience community to map the distribution of brain metabolites in vivo. Magnetic resonance spectroscopy imaging (MRSI) is often limited by either a poor spatial resolution and/or a long acquisition time which severely limits its applications for clinical or research purposes. We developed a novel acquisition-reconstruction technique combining fast 1H-FID-MRSI sequence accelerated by random k-space undersampling and a low-rank and total-generalized variation (TGV) constrained model. This framework was applied to the brain of four healthy volunteers. Following 20 min acquisition, reconstruction and quantification, the resulting metabolic maps with a 5mm isotropic resolution reflected the detailed neurochemical composition of all brain regions and revealed part of the underlying brain anatomy. Contrasts and features from the 3D metabolite distributions were in agreement with the literature and consistent across the four subjects. The successful combination of the 3D 1H-FID-MRSI with a constrained reconstruction enables the detailed mapping of metabolite concentrations at high-resolution in the whole brain and with an acquisition time that is compatible with clinical or research settings. Copy rights belong to original authors. Visit the link for more info

PaperPlayer biorxiv neuroscience
Gut microbial metabolite p-Cresol promotes autistic-like behaviors in mice through remodeling of the microbiota

PaperPlayer biorxiv neuroscience

Play Episode Listen Later May 19, 2020


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.18.101147v1?rss=1 Authors: Bermudez-Martin, P., Becker, J. J., Fernandez, S. P., Costa-Campos, R., Barbosa, S., Martinez Gili, L., Myridakis, A., Dumas, M. E., Bruneau, A., Cherbuy, C., Langella, P., Chabry, J., Barik, J., Le Merrer, J., Glaichenhaus, N., Davidovic, L. Abstract: Background: Perturbations of the microbiota-gut-brain axis have been identified in autism spectrum disorders (ASD), suggesting that the microbiota could be involved in the development or maintenance of abnormal social and stereotyped behaviors in ASD patients. Yet, the underlying mediators and mechanisms remain unclear. We hypothesized that microbial metabolites produced by the gut microbiota contribute to behavioral deficits in ASD. We focused on p-Cresol, a microbial metabolite previously described as abnormally elevated in ASD patients. Methods: Wild-type mice were chronically treated with p-Cresol in drinking water to mimic intestinal exposure. We combined behavioral phenotyping, electrophysiology, microbiota 16S sequencing and fecal microbiota transplantations to decipher the consequences of p-Cresol exposure. Results: We showed that p-Cresol selectively induced behavioral alterations reminiscent of ASD core symptoms: social behavior deficits, stereotypies and perseverative behaviors, but no changes in anxiety, locomotion or cognition. We further showed that p-Cresol decreases the activity of dopamine neurons in the ventral tegmental area (VTA), a key brain region for social reward processing. In addition, we reveal that p-Cresol remodels the intestinal microbiome, impacting specific bacterial taxa associated with social behavior deficits and stereotypies. We further demonstrated that social behavior deficits are transferred to control mice after transplantation of microbiota from p-Cresol-treated mice. Finally, both social interactions and VTA dopamine neurons activity were normalized in p-Cresol treated mice after transplant of microbiota from control mice. Conclusions: Our study suggests that the microbial metabolite p-Cresol could be involved in the development of autistic behaviors through remodeling of the gut microbiota. Copy rights belong to original authors. Visit the link for more info

JALM Talk Podcast
Cannabinol (CBN) Cross-Reacts with Two Urine Immunoassays Designed to Detect Tetrahydrocannabinol (THC) Metabolite

JALM Talk Podcast

Play Episode Listen Later May 11, 2020 8:40


Fempower Health
Dr Amy Beckley | Ovulation & Progesterone Metabolite: How they may play a role in your Fertility

Fempower Health

Play Episode Listen Later Apr 7, 2020 49:00


Hear an interview with Proov inventor and founder, Amy Galliher-Beckley, who created an at-home PdG, or progesterone metabolite, test to confirm ovulation. This is a completely innovative and novel diagnostic process for measuring PdG at home. We will learn about:The company and their product, Proov, Uncover why Amy created this test,The important role PdG levels plays in fertility, and The challenges women face in seeking help given the complex dynamics of our healthcare system. Fempower Health has developed a survey that leverages women's desire to help and advise other women based on their own experience and learnings from conditions like infertility, PCOS, endometriosis, and thyroid conditions. Go here to take survey and receive product discount as a thank you.Follow on Instagram and Facebook!#fempowerhealth #femcast NOTE: Fempower Health may receive a nominal fee for products purchased. The purpose of the podcast, however, is for education purposes only. Always go to a medical professional of your choosing.Support the show (https://www.patreon.com/fempowerhealth)

JACC Podcast
Long-term Changes in Gut Microbial Metabolite Trimethylamine N-Oxide and Coronary Heart Disease Risk

JACC Podcast

Play Episode Listen Later Feb 18, 2020 11:33


Commentary by Dr. Valentin Fuster

Precisione: The Healthcast
Using Metabolite Testing to Heal Your Gut

Precisione: The Healthcast

Play Episode Listen Later Jan 24, 2020 40:17


Erika Ebbel Angle received her Ph.D. in Biochemistry in 2012 from Boston University School of Medicine. She holds a B.S. from the Massachusetts Institute of Technology. In 2002 Erika founded Science from Scientists, an award-winning National nonprofit focused on improving Science, Technology, Engineering and Math (STEM) attitudes and aptitudes for children aged 9-13. She is also the co-founder and Director of Education for Robots In Service of the Environment (RSE), a non-profit organization whose mission is to apply robotic solutions to help solve environmental challenges. She is a member of the MIT visiting committee for the Dean of Undergraduate Education and is an Advisory Board member for the Ron Burton Training Village. She is also a STEM speaker for the U.S. Speaker Program at the U.S. Department of State. In 2018 she was awarded the Young Alumni award by Boston University. In 2017 she was the recipient of the Distinguished Alumni Award from Boston University School of Medicine Division of Graduate Medical Sciences. In 2014 the Boston Business Journal selected her as one of the 40 Under 40 business and civic leaders who are making a major impact in their respective fields in the Boston area. Her accomplishments have also been recognized by the Greater Boston Chamber of Commerce’s Pinnacle Awards for Emerging Executive. In 2013 the Boston Chamber of Commerce selected her as one of the Ten Outstanding Young Leaders in Boston. Selected by L’Oreal Paris as a 2007 Woman of Worth for her work with Science from Scientists, Erika has been featured on Lifetime TV and Nova Science Now on The Secret Lives of Scientists and Engineers. She is the host of The Dr. Erika Show, an educational science TV show for children. Erika served as a Commissioner for the MA Commission on the Status of Women. Erika was Miss Massachusetts 2004 in the Miss America Scholarship program. Outside of work, Erika enjoys SCUBA diving, skiing and, a graduate of the San Francisco Conservatory of Music, continues her lifelong passion for classical piano. She is married to Colin Angle, CEO of iRobot. What you will learn from this episode: 1) How a simple blood test can give you insight into your gut health. 2) What is the metabolome and why it is important? 3) Are stool tests good enough to teach us about our gut health? 4) How you can improve your fitness performance but learning about your gut health 5) What interventions you can make to improve your health and longevity How to learn more about our guest: Full Bio: https://ixcela.com/team-bios/erika-angle-phd.html Connect with Erika ● Blog: Erika Ebbel Angle ● LinkedIn: Erika Ebbel Angle ● Twitter: @DoctorErika A special thank you: As a special thank you for listening to this episode, Ixcela has been so kind as to give us a discount code which you can use to get a 10% discount. Go to ixcela.com and use the code “IxcelaWellness10” to check it out! Please enjoy, share, rate and review our podcast and help us bring the message about precision health care to the world!

Neil Rogers Show
Neil Rogers Show (May 26, 1999)

Neil Rogers Show

Play Episode Listen Later Oct 9, 2019 161:43


Metabolite, more OJ, YT embed issue

Steroids Podcast
Best Cutting Steroid Cycle - The Steroids Podcast Episode 17 Special 90 Minute Episode

Steroids Podcast

Play Episode Listen Later Sep 21, 2019 84:55


Ask Your Questions For the Next Episode at - https://steroidspodcast.com 0:00 Ultimate Guide to Roids 4:45 My Experience Writing the Best Bodybuilding Book Ever Released 7:50 Testosterone Cypionate 300mg Equipoise 300mg Primobolan 500mg per week cycle 11:25 Powers of Primbolan 13:13 How to tell Real vs. Fake Bayer Primobolan 16:16 Primobolan Nitrogen Retention Effects 18:00 Trenbolone Side Effects 18:56 What it means to “Go Flat” in Bodybuilding 20:11 Primobolan Side Effects 20:55 Trenbolone vs Primobolan 22:30 Realistic Dosages of Anabolic Steroids for Bodybuilding 24:42 How Long Does It Take Anadrol to Kick In 26:41 What is EPO and Blood Doping in Cycling and Endurance Sports 28:27 Best Pre workout Drink for Cardio 30:16 How Come Dick is Smaller on Tren? 32:05 Trenbolone Jack of All Spades Hormone in the Penis 33:10 Tren Shrinks Your Balls More Than Any Other Steroid Some Guys Lose Their Nuts and Cannot Find Them Up Inside Their Abdomen 34:00 Trenbolone “Empty Sac” Side Effect 34:50 How to Spot a Tren Abuser 35:10 Trenbolone Night Sweats 36:05 Primobolan Minimum Effective Dosage 36:38 High Reps vs Low Reps For Dense Muscle Growth with Steroids 38:20 What it Means to Optimize your Training Diet and Steroids 39:37 Indicators of Progress in the Gym 41:19 Middle Age TRT Guy runs two cycles of Equipoise and Primobolan 16 weeks per year 43:18 What is a Metabolite of a Steroid 44:45 Methyl Trenbolone Methyl Deca Oral Stack 47:05 Methyltrienolone in Scientific Experiments 48:10 Methy Tren Effects and Stereotypes 49:49 First Steroid Cycle 250mg Testosterone Enanthate 10 Weeks with HCG for PCT 51:00 How to Prevent Permanent Gyno “Bitch Tits” 53:20 Best PCT for Steroid Cycle 56:10 Bad Reaction and Swelling from Synthetic OIls in UGL Gear 56:30 What is a UGL 58:20 How to Prevent Infection from Steroids Injection 59:52 How Long Does Tren Ace take to Kick In 1:02:00 Best Fat Burning Steroids 1:03:40 HGH Permanent Gains and Side Effects 1:05:18 Reality of HGH Gains and Going off Steroid Cycle 1:05:40 Growth Hormone Side Effects 1:06:47 Anavar Only Cycle Libido and Penis 1:09:03 500mg Sustanon 300 Propionate 300 Trenbolone 300 Masteron 50mg per day Dbol Cycle 1:10:55 Best Way to Prevent Estrogen Side Effects 1:11:47 Beginner Cutting Cycle 1:15:00 Masteron Libido Effect 1:17:30 20mg Dianabol 25mg Anadrol Methyl Testosterone 5mg Tablet Explanation 1:19:40 Aromasin Exemestane Side Effects 1:20:10 What “Half Life” of Steroid Means This Podcast is for entertainment and conversational purposes only. This author does not support the use of illegal performance enhancing drugs. If any substances mentioned in this video are illegal in your country do not use them. Consult a doctor before beginning any exercise or supplement routine. Do not take anything mentioned in this video as advice. It is simply conversation, not advice.

MAX MPS RADIO
MAX MPS RADIO #73: Dr. Mike Israetel - Overload Training Modalities Ep. 2 - Metabolite Techniques

MAX MPS RADIO

Play Episode Listen Later Sep 9, 2019 86:52


Dr. Mike Israetel, Ph.D. in Sport Physiology and Co-Founder of Renaissance Periodization is back on the show. In this episode Mike dives deeper into the overload training modalities including higher rep sets and metabolite techniques like giant sets, myo reps, drop sets and BFR training. These topics will be covered in depth in his upcoming book “Scientific Principles of Hypertrophy Training” which will be released next year. 01:23 What exactly is metabolic stress? Where would you place its importance in contrast to mechanical tension in hypertrophy training? 5:50 Giant Sets 16:07 Myo Reps 42:55 Drop Sets 46:24 How do you program Drop Sets? 50:27 Is there a bottom range intensity for drop sets? 52:45 How do you program relative intensities for metabolite techniques? 01:01:44 Supersets 01:02:20 Compound alternating supersets 01:14:12 Blood Flow Restriction Training (BFR) 01:17:32 Do you think there is a specific advantage to BFR vs. just normal low load training? 01:18:49 How do you track sets for metabolite techniques? 01:23:24 What Mike is up to in the next few months Mikes Facebook: https://www.facebook.com/michael.isra... Mikes Instagram: https://www.instagram.com/rpdrmike/ Renaissance Periodization: https://renaissanceperiodization.com Renaissance Periodization Instagram: https://www.instagram.com/rpstrength/ RP+: https://renaissanceperiodization.com/... How much should I train: https://renaissanceperiodization.com/...... ______________________________________________ Thanks for listening/watching! If you liked the podcast please like, comment, share and subscribe to the channel! This podcast is also available on all other streaming-platforms: Itunes: https://itunes.apple.com/de/podcast/m... Soundcloud: https://soundcloud.com/janfrisse/ Spotify: https://open.spotify.com/show/1OmzAJu... ______________________________________________ Webseite/Website: http://janfrisse.de Online Personal Training: http://janfrisse.de/online-personal-t... Kostenloses Beratungsgespräch/Free Skype Consulting: http://janfrisse.de/kontakt Instagram: https://www.instagram.com/janfrisse Youtube: https://www.youtube.com/channel/UCX_O... Facebook: https://www.facebook.com/janfrissept E-Mail: coaching@janfrisse.com ______________________________________________ For my English audience: My name is Jan Frisse a full time online coach located in Essen, Germany and I am an intern with Dr. Mike Israetel. You are more than welcome to join! I will regularly release English content with the top scientists, experts, coaches and athletes in the field of the evidence-based fitness industry. Just keep in mind that this is a bilingual podcast, so there will be German content since my main target audience is Germany. I’m still absolutely happy to have you on here as well so you’re more than welcome to stay! "MAX MPS RADIO" ist ein bilingualer Podcast mit evidenz-basierten Content zum Thema Bodybuilding, Fitness, Ernährung und den Wissenschaften dahinter! Jan interviewt die Top-Experten im Feld der evidenzbasierten Fitness-Industrie und produziert Co-Host Serien mit anderen Coaches und Athleten!

Breastcancer.org Podcast
Metabolite Markers -- Heard in the Halls: Voices From the 2019 American Society of Clinical Oncology Annual Meeting

Breastcancer.org Podcast

Play Episode Listen Later Jun 5, 2019 3:35


Clinical Chemistry Podcast
Validation of a Metabolite Panel for a More Accurate Estimation of Glomerular Filtration Rate Using Quantitative LC-MS/MS

Clinical Chemistry Podcast

Play Episode Listen Later Mar 26, 2019 8:33


Glomerular filtration rate, or GFR, is generally accepted as the best overall index of kidney function, and a decrease in GFR has important implications for prognosis in patient management.  GFR is most commonly estimated by calculation, using the serum concentration of an endogenous filtration marker such as creatinine and demographic variables such as age, sex, and race.  In the March 2019 issue of Clinical Chemistry, a paper investigated the possibility of developing a more accurate estimate of GFR, using a panel of metabolites measured by quantitative liquid chromatography, tandem mass spectrometry without creatinine, cystatin C, or demographic variables.

Gesünder mit praktischer Medizin
#10 Schlafmittel - 2 Mio. Abhängige in Deutschland

Gesünder mit praktischer Medizin

Play Episode Listen Later Jan 27, 2019 33:39


In dieser 3. Podcast-Folge zum Thema Schlaf spricht Prof. Dr. med. Harald Schmidt über Schlafmittel. Da das Thema doch recht umfangreich ist geht es heute um die chemischen Substanzen und das große Problem von 2 Millionen Schlafmittelabhängigen in Deutschland In einer weiteren Folge um die Pflanzlichen. Der neueste Stand der Medizin, Evidenz-basiert und direkt umsetzbare praktische Impulse warten auf Sie. //   Vorbemerkungen //  Wann? //  Ich sag’s gleich, wie auch schon in der letzten Folge zur Schlafhygiene, ich bin kein Freund von Schlafmitteln. Ausnahmen sind zwei nachvollziehbare Gründe: Jetlag ein emotional stark bewegendes/belastenden Erlebnis. //   Wann nicht //  Schlaftabletten zu verwenden, um z.B. trotz der Nervosität vor einer Prüfung schlafen zu können, ist hingegen keine gute Idee. Fast alle Schlafmittel können bis in den Tag hineinwirken und die körperliche und geistige Leistungsfähigkeit stark einschränken. //   Abhängigkeit //  Schlafmittel sind in aller Regel nicht für die Selbstbehandlung geeignet. Das gilt vor allem für verschreibungspflichtige Schlafmittel wie Benzodiazepine, die schnell eine Abhängigkeit verursachen können. Sie können dann nicht mehr ohne Schlafmittel schlafen. Die Schlafmittel-Abhängigkeit wird zur Ursache Ihrer Schlafstörung oder Sie haben nun zwei Schlafstörungen. Aber auch nicht verschreibungspflichtige, aber apothekenpflichtige chemische sowie pflanzliche Schlafmittel können zumindest psychisch abhängig machen. Etwa die Hälfte der Benutzer von Schlafmitteln entwickelt nach Angaben der Deutschen Hauptstelle für Suchtgefahren eine Schlafmittel-Abhängigkeit. Das sind allein in Deutschland 400.000 Schlafmittel-Süchtige jedes Jahr. Insgesamt gelten etwa 2 Millionen Menschen als abhängig von Schlafmitteln. Etwa die Hälfte dieser Menschen konsumiert die häufig verschriebenen Benzodiazepine. Als besonders anfällig für Medikamentensucht und Schlafmittelmissbrauch gelten Frauen. Zahlreiche Studien legen nahe, dass Schlafmittel die Lebenserwartung deutlich verkürzen können. //   Nur kurzfristig! //  Schlafmittel sind nicht für den langfristigen Einsatz gedacht. Ohne ärztliche Weisung sollten Sie Schlafmittel nie länger als eine Woche anwenden. Sollte Ihr Arzt immer wieder ohne Nachfragen Schlafmittel-Rezepte ohne besondere Diagnose ausstellen, wenden Sie sich am besten an einen anderen Arzt, um ihre Schlafstörungen besser zu behandeln und wenden Sie die Tipps meiner vorherigen Podcast-Folge “Endlich besser schlafen” an. //   Das ideale Schlafmittel... //  … gibt es nicht. Es müsste einen Schlaf bewirken, der sich vom natürlichen Schlaf in nichts unterscheidet. Alle heute verwendeten Mittel verändern jedoch die Schlafstadien und die messbaren Hirnströme. GABAA //  Die meisten Schlafmittel wirken über einen Ionenkanal der durch den Neurotransmitter γ-Aminobuttersäure reguliert wird. γ-Aminobuttersäure = GABA und hiervon der Typ A also GABAA. Schlafmittel binden entweder an GABA Bindungsstelle oder an eine eigene. Dadurch kommt es zum Einstrom negativer Cl Ionen. Da Nervenzellen durch den Einstrom positiver Ionen aktiviert werden, hemmt dies also die Nervenzellen. GABAA. Ist dabei der wichtigste hemmende Rezeptor im zentralen Nervensystem. Dadurch wird zwar Schlaf induziert, aber auf Kosten des erholsamen REM- und Tiefschlafs. Nach Absetzen vieler Schlafmittel gibt es zunächst einen überschießenden REM-Schlaf während sich der Tiefschlaf nur langsam erholt. Übrigens, auch Alkohol bindet an diesen GABAA-Rezeptor wodurch sich dessen sedierende Wirkung erklärt; aber ich erwähnte unter Schlafstörungen dass Alkohol ein denkbar ungeeigneter Schlafförderer ist, da dessen Metabolite während der Nacht den Schlaf stören und Durchschlafen verhindern. //   Verschreibungspflichtige chemische Arzneimittel: //   Barbiturate  //  Nicht mehr als Schlafmittel,...

Pediatric Research Podcast
Association between metabolite composition and metabolic risk across adolescence

Pediatric Research Podcast

Play Episode Listen Later Jan 25, 2019 10:02


Metabolomics has the potential to identify specific targets for primary prevention of metabolic disease. Studies in adults have shown that lean vs obese people show distinct differences in their metabolite composition, sometimes preceding the development of established risk factors associated with metabolic disease. The literature in paediatric populations, however is scant. In this episode, we speak to Prof. Wei Perng, who during her time at the University of Michigan School of Public Health, examined the associations between metabolite composition and metabolic risk across adolescence. See acast.com/privacy for privacy and opt-out information.

Journal of Clinical Oncology (JCO) Podcast
The End of ENDoxifen Metabolite and CYP2D6 Testing in Tamoxifen-Treated Women?

Journal of Clinical Oncology (JCO) Podcast

Play Episode Listen Later Jan 24, 2019 6:05


This JCO Podcast provides observations and commentary on the JCO article “Tamoxifen pharmacogenetics and metabolism: Results from the prospective CYPTAM study” by Sanchez-Spitman et al. My name is Vered Stearns, and I am a Professor of Oncology and Co-Director of the Breast and Ovarian Cancer Program at the Kimmel Cancer Center at Johns Hopkins in Baltimore, Maryland. My oncologic specialty is medical oncology. In the paper that accompanies this podcast, the authors report results of a prospective clinical study designated CYPTAM, which was designed to correlate endoxifen serum concentrations and outcomes of women prescribed adjuvant tamoxifen. The investigators enrolled 667 women with breast cancer who were initiating tamoxifen or who have been on tamoxifen for fewer than 12 months. The investigators obtained blood samples for CYP2D6 genotyping using the Amplichip CYP450 Test, and measured steady state concentrations of endoxifen with a high-performance liquid chromatography-tandem mass spectrometry. Co-primary endpoints included association of recurrence-free survival with endoxifen concentrations and with CYP2D6 genotypes. The patients were censored at the time of tamoxifen-discontinuation in case of a transition to an aromatase inhibitor. Several additional endpoints included disease-free survival, complete relapse-free survival, complete disease-free survival and overall survival. The statistical analysis plan was designed as a gate-keeper analysis for the co-primary objectives. Only if an association was found with a p-value below 0.05, were the remaining objectives considered.   The authors were not able to demonstrate an association between endoxifen concentrations and recurrence-free survival on tamoxifen. They also were not able to demonstrate an association either when exploring endoxifen concentrations in quartiles or when considering other thresholds. Likewise, there was no association between CYP2D6 genotypes and recurrence-free survival.   Almost two decades ago, researchers recognized that the absence or inhibition of the CYP2D6 enzyme is associated with very low concentrations of endoxifen, a potent and abundant anti-estrogen metabolite of tamoxifen. Whether low concentrations of endoxifen predict an inferior survival outcome has not been definitively determined. Multiple retrospective and small prospective studies evaluated CYP2D6 genotypes and survival outcomes and have provided mixed evidence. Clinicians have, therefore, wondered whether CYP2D6 genotype testing or endoxifen monitoring will assist in treatment recommendations. The CYPTAM investigators attempted to prospectively correlate endoxifen serum concentrations and outcomes for women taking tamoxifen.   The CYPTAM study is associated with several limitations, and, therefore, it does not provide a definitive answer to the controversy. For example, women were enrolled in the study either before starting tamoxifen or up to 12 months after initiation of the drug. This strategy could have led to incomplete baseline data and to the exclusion of individuals with early recurrences. In addition, about two-thirds of study participants transitioned to aromatase inhibitors following a short course of tamoxifen. The sequential administration of tamoxifen and aromatase inhibitors is superior to tamoxifen alone. Some of the patients who transitioned to aromatase inhibitors could have suffered a recurrence had they have stayed on tamoxifen alone. Furthermore, the authors did not have information regarding concomitant CYP2D6 inhibitor use. CYP2D6 inhibitors are commonly co-administered with tamoxifen and can contribute to misclassification of the CYP2D6 phenotype.    The challenge moving forward is that single agent adjuvant tamoxifen is rarely used. Most postmenopausal women with hormone receptor-positive breast cancer are recommended an  aromatase inhibitor instead of, or in sequence with, tamoxifen. Premenopausal women with high risk hormone receptor-positive tumors are recommended ovarian suppression with tamoxifen or an aromatase inhibitor. Women prescribed tamoxifen alone are usually at extremely low risk of recurrence, and a prospective study in this group of women will require a large number of participants to demonstrate differences between phenotypes. Given current practice, it may not be feasible to fully determine the role of endoxifen concentrations and CYP2D6 genotypes as predictors of tamoxifen efficacy.   Retrospective analyses that used samples obtained through large prospective studies, such as the Arimidex, Tamoxifen, Alone or in Combination and the Breast International Group 1-98, failed to demonstrate an association between CYP2D6 phenotypes and survival outcomes. Taken together, the data at present are insufficient to recommend CYP2D6 testing or analysis of metabolic profile in women for whom tamoxifen is considered. Indeed, clinical guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network do not recommend CYP2D6 genotyping. Moving forward, prospective studies of altered metabolism due to single nucleotide polymorphism, or administration of inhibitors, should be considered in clinical trials of standard and novel agents as these can lead to differences in drug efficacy and toxicity.   This concludes this JCO Podcast. Thank you for listening.

Anti-Doping Science Podcast
Ep.35 - Jon Jones & The Long Term Metabolite for Turinabol

Anti-Doping Science Podcast

Play Episode Listen Later Dec 27, 2018 54:44


Earlier this week it was announced that Jon Jones’s urine produced an Adverse Analytical Finding (AAF) for a long-term metabolite for the Anabolic Androgenic Steroid (AAS) Chlorodehydromethyltestosterone (DHCMT) – which is known by it’s trade name Oral-Turinabol. This is the 2nd time this long-term metabolite has been discovered inside Jon Jones urine. This podcast covers a detailed discussion on Jon Jones’s previous anti-doping rule violation for Clomiphene, his 2nd antidoping rule violation for the M3 metabolite and a discussion of the reappearance of this metabolite in his urine. I also discuss the research that has been conducted so far on the long-term metabolite (M3 metabolite) of Turinabol. Links to all reference material is below: Article on Jon Jones Fighting History: https://mmajunkie.com/2018/12/ufc-232-preview-jon-jones-career-statistics-facts Article on Atypical Finding announced in December 2018: https://mmajunkie.com/2018/12/jon-jones-drug-test-atypical-result-ufc-232-moved-to-los-angeles-gustafsson-dana-white Article on Jones’s 1st AAF for Clomiphene: http://www.espn.com/mma/story/_/id/25608180/jon-jones-long-winding-road-ufc-232 Article on Clomiphene https://anabolic.org/clomid-clomiphene-citrate/ USADA High Risk List of Supplements & Supplement 411: https://www.usada.org/substances/supplement-411/ USADA Arbitration Report on 2nd AAF for M3 Metabolite for Turinabol: https://ufc.usada.org/wp-content/uploads/Final-Redacted-Award-Jones-and-USADA.pdf Discovery of the M3 metabolite in 2012 by Sobolevsky & Rodchenkov: https://www.ncbi.nlm.nih.gov/pubmed/22142641 Critique of Sobolevsky & Rodchenkov’s research: https://www.researchgate.net/publication/305489931_Novel_metabolites_of_turinabol_WADA_moving_toward_illusions Synthesis of the M3 metabolite in 2018 (also discussing the extension in detection from the long term metabolite): https://pubs.rsc.org/en/content/articlelanding/2018/ob/c8ob00122g#!divAbstract Confirmation of the M3 metabolite in 2018: https://www.ncbi.nlm.nih.gov/pubmed/29570240

The Revive Stronger Podcast
084: The improvement season - Metabolite Frequency

The Revive Stronger Podcast

Play Episode Listen Later Dec 18, 2018 61:43


The Ultimate Coach Seminar 2019 http://revivestronger.com/the-ultimate-coach-seminar/ This time we're talking about heart health, living life, things such as scars and tattoos for competing Timestamps: 35:21 Operation scars detrimental? 39:50 Metabolite technique frequency 47:45 how to gauge when to make adjustments Thanks, please comment, like and subscribe! COACHING: http://revivestronger.com/online-coaching/ WEBSITE: http://www.revivestronger.com FACEBOOK: http://www.facebook.com/revivestronger TWITTER: http://www.twitter.com/revivestronger INSTAGRAM: http://www.instagram.com/revivestronger MYFITNESSPAL: http://www.myfitnesspal.com/food/diary/snhall1990 YOUTUBE: https://www.youtube.com/watch?v=7GTnAOzvPV4 __ Stay up to date with the latest research! MASS (Research Review): • https://goo.gl/c7FSJD RP+ Membership: • https://ob262.isrefer.com/go/plus/Steve90/ __ Books we recommend! RP Books • http://bit.ly/2vREaH0 Scientific Principles of Strength Training • http://bit.ly/2w3th4D Renaissance Periodization Diet Ebook • http://bit.ly/2wGuuMU Understanding Healthy Eating • http://bit.ly/2uAxFZ8 RP + Members site • https://ob262.isrefer.com/go/plus/Steve90/ __ Recommended supplements: Denovo Nutrition (use code STEVE) • https://denovosupps.com?aff=6 __ When you're interested in online coaching, please go visit our website and follow the application form: http://www.revivestronger.com/online-coaching/

The Peter Attia Drive
#31 - Navdeep Chandel, Ph.D.: metabolism, mitochondria, and metformin in health and disease

The Peter Attia Drive

Play Episode Listen Later Dec 3, 2018 142:24


In this episode, Nav Chandel, a professor of medicine and cell and molecular biology at Northwestern University, discusses the role of mitochondria and metabolism in health and disease. Nav also provides insights into the mitochondria as signaling organelles, antioxidants, and metformin’s multifaceted effects on human health, among many topics related to well-being. We discuss: What got Nav interested in mitochondria [5:00]; Reactive oxygen species (ROS) [16:00]; Antioxidants: helpful or harmful? [20:00]; Mitochondria as signaling organelles [22:00]; Hydrogen peroxide (H2O2) [25:00]; Mitochondrial DNA [28:00]; Mitochondria and aging [45:00]; Metformin [52:45]; Metformin and the gut microbiome [54:00]; Metformin as complex I inhibitor and the importance of the NADH/NAD ratio [1:01:00]; Anticancer benefits of metformin [1:07:45]; Mitochondrial function is necessary for tumorigenesis [1:15:00]; Are somatic mutations the result of mitochondrial dysfunction? [1:31:30]; Vitamins and antioxidants [1:37:00]; Targeting inflammation in disease [1:43:00]; NAD precursors [1:45:45]; MitoQ [1:52:00]; Metabolite toxicity [1:56:30]; Cortisol and healthy aging [2:02:00]; Nav turns the tables and asks Peter how he deals with the “So what should I eat?” question during social encounters [2:09:00]; and More. Learn more at www.PeterAttiaMD.com Connect with Peter on Facebook | Twitter | Instagram.

Addiction Medicine: Beyond the Abstract
Perinatal Pharmacokinetics and Serum Methadone/Metabolite Ratios

Addiction Medicine: Beyond the Abstract

Play Episode Listen Later Nov 27, 2018 11:38


  In episode nine of Addiction Medicine: Beyond the Abstract, we are joined by Dr. John McCarthy, an associate professor of psychiatry and volunteer clinical faculty at the University of California Davis. In his recent study, Dr. McCarthy and his colleagues examined the significance of serum methadone/metabolite ratios (or MMRs). In particular, they looked at the changes in these ratios for the expecting mother throughout pregnancy and sought to use these ratios to objectively guide methadone dosing. To read the full article, click here. 

Cancer Grand Rounds Lectures from the Norris Cotton Cancer Center Podcasts
Identifying and targeting metabolite detoxifying enzymes to selectively poison cancer cells

Cancer Grand Rounds Lectures from the Norris Cotton Cancer Center Podcasts

Play Episode Listen Later Feb 28, 2018 59:30


Norris Cotton Cancer Center Grand Rounds presented on February 27, 2018 Dohoon Kim, PhD Assistant Professor, University of Massachusetts Medical School

BacterioFiles
BacterioFiles 327 - Microbe Metabolite Meliorates Malaise

BacterioFiles

Play Episode Listen Later Feb 5, 2018 9:49


This episode: Gut microbes in mice break down plant foods and produce molecules that stimulate the immune system to resist influenza! Thanks to Drs. Ashley Steed and Thaddeus Stappenbeck for their contributions! Download Episode (9 MB, 9.8 minutes) Show notes: Microbe of the episode: Bougainvillea chlorotic vein banding virus News item Journal Paper: Steed AL, Christophi GP, Kaiko GE, Sun L, Goodwin VM, Jain U, Esaulova E, Artyomov MN, Morales DJ, Holtzman MJ, Boon ACM, Lenschow DJ, Stappenbeck TS. 2017. The microbial metabolite desaminotyrosine protects from influenza through type I interferon. Science 357:498–502. Other interesting stories: Nanobots with propellers modeled after bacterial flagella Embedding useful bacteria into "ink" used to print 3D structures Controlling behavior of individual bacteria using a computer Exercise alone can affect microbiota Microbes in ISS are similar to microbes in Earth homes   Email questions or comments to bacteriofiles at gmail dot com. Thanks for listening! Subscribe: iTunes, RSS, Google Play. Support the show at Patreon, or check out the show at Twitter or Facebook

Research Features Audio
Fighting depression with Ketamine

Research Features Audio

Play Episode Listen Later Oct 25, 2017 7:53


Metabolite created as the body breaks down Ketamine is responsible for its rapid antidepressant action explains Dr Todd Gould from the University of Maryland School of Medicine.   To read the full article click here.

The Revive Stronger Podcast
058: Mike Israetel - Q&A - Properly Programming for Metabolite Training

The Revive Stronger Podcast

Play Episode Listen Later Jul 10, 2017 54:09


Another famous Q&A with Dr.Mike, from metabolite training in & out & how to identify if you're a non-responder to something. ~ 02:43 Where to place metabolite training & how to progress metabolite training?? 25:26 Could Mike discuss some ways he's found for improving digestion, to handle the quantities of food required in a bulk. 39:08 What value do you place on intra-workout nutrition? 44:30 Can a tight muscle restrict hypertrophy? Less ROM etc... & if so how might you deal with this in training? (SKIPPED) 45:01 How can one identify a non-responder to hypertrophy training? What can they do? Given that they eat well and train well. ~ • Facebook Group to ask Q's: https://www.facebook.com/groups/revivestronger/ • Mike's Facebook: https://www.facebook.com/michael.israetel • Mike's IG: https://www.instagram.com/rpdrmike/ • RP+: https://renaissanceperiodization.com/rpplussignup ~ COACHING: www.revivestronger.com/online-person-training/ WEBSITE: www.revivestronger.com SNAPCHAT: www.snapchat.com/add/revivestronger FACEBOOK: www.facebook.com/revivestronger TWITTER: www.twitter.com/revivestronger INSTAGRAM: www.instagram.com/revivestronger MYFITNESSPAL: www.myfitnesspal.com/food/diary/snhall1990 YOUTUBE: https://www.youtube.com/watch?v=xAHMjbsLE8U

Evolution Radio Show - Alles was du über Keto, Low Carb und Paleo wissen musst

In Folge #115 Das Video der aktuellen Folge direkt auf Youtube öffnen Bitte beachten Sie auch immer den aktuellen "Haftungsausschluss (Disclaimer) und allgemeiner Hinweis zu medizinischen Themen" auf https://paleolowcarb.de/haftungsausschluss/ #geNUSS[explosion] von [næhr:sinn] - das low carb knusper nuss müsli [næhr:sinn] geNUSS[explosion] ist ein hochwertiges low-carb* Müsli und besteht zu 100% aus natürlichen Zutaten. Es ist gut als Frühstück und Snack und hat nur 13,7g verwertbaren Kohlenhydraten auf 100g. Es ist getreidefrei und sojafrei. Perfekt für den Start in den Tag. Wir verarbeiten nur hochwertigste, nährstoffreiche Zutaten, die dich länger satt machen und nachhaltig mit Energie versorgen. Wir nutzen ballaststoffreiche Kokosnuss, Erdmandel und heimische Nüsse. Mehr darüber erfährst du auf lowcarbmüsli.at oder auf Amazon.de Und nicht vergessen: Wenn du uns auf Youtube siehst, und wenn du es noch nicht getan hast, dann abonniere unseren Kanal „Evolution Radio Show“ Wenn du das Podcast hörst, dann findest du die Links für Apple iTunes und Android hier auf unserer Homepage Diese Episode wird gesponsert/unterstützt von BRAINEFFECT Suchst du nach einem Weg schneller in Ketose zu kommen? Dann ist ROCKET C8 von BRAINEFFECT genau das Richtige für Dich. Wie der Name schon sagt besteht das ROCKET C8 aus 100% C8 Fettsäuren (also Caprylsäure), welche die optimalste der mittelkettigen Fettsäuren ist. Es ist geschmacksneutral, und daher kann man es wirklich überall einsetzen.Egal ob im Cafe, auf dem Salat oder in Smoothies etc. Der Vorteil daran ist, dass auch Ketonkörper gebildet werden können, wenn du Kohlenhydrate zu dir genommen hast. Mit dem Gutscheincode Evolutionradioshow bekommt ihr 20% auf alle Produkte im BRAINEFFECT Shop unter http://www.brain-effect.com/ Transkript der Folge Der Wunsch nach der Süße ohne Reue ist groß. Im Laufe der letzten Jahrzehnte haben wir einige Substanzen entdeckt, oder im Labor erzeugt, die Süß schmecken, ohne jedoch Kalorien zu liefern. Manche dieser Substanzen haben sich als Gesundheitsschädlich erwiesen, manche scheinen unbedenklich zu sein. Als “neue” Süßstoffe am Markt haben sich in den letzten Jahren, die sogenannten Zuckeralkohole etabliert. Die Ergebnisse einer aktuelleren Studie regen zur Sorge an - könnte Erythrit etwas mit Übergewicht zu tun haben? Bevor wir auf den eigentlichen Artikel eingehen, möchte ich ein paar Worte zu Zucker und Süßstoffen generell loswerden. Generell ist erstrebenswert sich Süßigkeiten und Naschen abzugewöhnen. Egal ob Zucker oder Süßungsmittel, der Griff zum Goodie sollte die Ausnahme bilden. Nun zur aktuellen Studie: [Hootman, Katie C., et al. "Erythritol is a pentose-phosphate pathway metabolite and associated with adiposity gain in young adults." Proceedings of the National Academy of Sciences (2017): 201620079.](http://www.pnas.org/content/114/21/E4233.abstract) Die Arbeit von Katie Hootman und Kollegen hat zu einem großen Aufschrei in der LCHF Gemeinde geführt. Erythrit soll zu Übergewicht führen, oder Übergewicht begünstigen? Kann denn das sein? Die Erythrit-Gegner haben auch nicht lange auf sich warten lassen und in der Studie eine Bestätigung der Grundsätzlichen Skepsis dem Zuckeralkohol mit dem suspekt wirkenden Namen gesehen. Erythrit, kann ja nicht gut sein, ist ja nicht „natürlich“ – oder doch? Aber dazu später. Erst einmal zur eigentlichen Studie. Was wurde gemacht und was waren die Ergebnisse?   Methode Untersucht wurden Collage Studenten (n=172) im Alter zwischen 18-19 Jahren. Die Auswahl der Teilnehmer war Randomisiert und auf gleichmäßige Verteilung der Geschlechter wurde geachtet. Erfasst wurden anthropometrische Daten, Blutplasma (nicht nüchtern) sowie die Körperzusammensetzung via DXA (dual -energy x-ray absorptiometry). Untersucht wurden verschiedene Metabolite (Stoffwechselprodukte) hinsichtlich ihrer möglichen Rolle als Prädiktor für die Entwicklung von Übergewicht. Die Studenten wurden dann hinsichtlich ihrer Fettmasse und dem Hba1c eingeteilt. Daraus ergaben sich 4 Phänotyp Gruppen: Fettmasse Zunahme in der Bauchregion (incident central adiposity gain) Stabiles Fettmasse (stable adiposity) Hba1c in den Top 25% Hba1c in den untersten 10% Ergebnisse der Studie Nach einem Jahr haben 75% der Studenten an Körpergewicht zugelegt. (>0.5kg). Bei 66 Teilnehmern konnten die Forscher eine Fettzunahme in der Bauchregion feststellen. Metabolite als Prädiktor für Fettzunahme in der Bauchregion Die Forscher haben sich verschiedene Metabolite angesehen. Neben Erythritol, auch Fructose, Lactat, Valin und Leucin. Es gab Unterscheide in allen genannten Metaboliten zwischen den Gruppen, allerdings erreicht nur Erythritol das Signifikanzlevel. Interessant ist, dass die höchsten Eryhtritol Konzentrationen in der Gruppe zu finden waren, mit der geringsten Zunahme an Bauchfett. Während die niedrigsten Erythritol Werte in der Gruppe mit den Größten Veränderungen der Bauchfettmasse zu beobachten waren. Eigensynthese von Erythritol Nimmt man Erythrit über die Nahrung auf, dann werden 90 – 95% über den Harn ausgeschieden. 5 – 10% werden zu Eryhtronat oxidiert. Der menschliche Körper ist allerdings auch in der Lage Erythritol selber aus Glucose zu synthetisieren. Diskussion Die Autoren der Studie fanden signifikante Unterschiede zwischen den Gruppen was Fructose und Erythritol Konzentrationen betrifft. Sie sehen eine positive Assoziation zwischen Erythritol im Plasma und dem Auftreten von Fettmassezuwachs in der Bauchregion. Weitere Untersuchungen werden benötigt um diese Ergebnisse verstehen zu können.   Assoziation ist kein ursächlicher Zusammenhang Soweit die Kurzfassung der Studie. Bevor wir die Ergebnisse weiter besprechen und in wie weit sie für uns relevant sind, ein paar Worte zu statistischen Zusammenhängen. Die Forscher sehen eine positive Assoziation. Das bedeutet, dass Wert A und Wert B gemeinsam auftreten, einen ursächlichen Zusammenhang kann man aus dieser Studie noch nicht ableiten. Wir können also nicht sagen: A verursacht B. Endogene Produktion vs. Exogene Exposition Was die Autoren der Studie auch bemerken ist, dass wir noch nicht wissen, was das mit der exogenen Aufnahme von Erythrit zu tun hat, und ob überhaupt. Das Erythrit, das die Autoren in den Blutproben gefunden haben, stammt ja aus endogener Synthese, und zwar aus Glucose. Jetzt kommen wir zu einem interessanten Punkt. Die Autoren schreiben, dass in bisherigen Studien nicht gezeigt werden konnte, dass Menschen Erythritol endogen synthetisieren können. Sie zitieren dazu eine Studie aus dem Jahr 1993 von Hiel et. al.[1] Dies scheint jedoch nicht mehr ganz aktuell zu sein. Bei weiterer Recherche stellt sich heraus, dass Erythrit von Föten diverser Wiederkäuer selbst produziert wird[2], und nicht nur von Wiederkäuern, sondern auch vom Menschen.   Erythrit und andere Polyole im menschlichen Fötus und der Plazenta 2005 im Journal „Pediatric Research“, welches zu Nature Publishing gehört, veröffentlichte Brusati et al. eine Arbeit mit dem Titel: „Fetal and Maternal Non-glucose Carbohydrates and Polyols Concentrations in Normal Human Pregnancies at Term“[3]. Andere Zucker und Zuckeralkohole wie Inositol, Sorbitol und Erythrit, sind wichtige Energielieferanten für das Ungeborene. Diese Zuckeralkohole finden sich in signifikanten Mengen in der Nabelschnur und, in geringeren Mengen, auch im Blut der Mutter. Besonders interessant ist, dass es zwischen Mutter und Fötus einen relativ großen Konzentrationsgradienten gibt. Dies unterstützt die Annahme, dass der Fötus selbst Polyole (Inositol, Sorbito und Erythritol) synthetisiert. […] Finally, that polyol concentrations are elevated sufficiently in fetal blood to lead to the establishment of relatively large fetal–maternal concentration gradients for polyols such as inositol, sorbitol, and erythritol suggests that the trophoblast may be relatively impermeable to these compounds. The presence of large fetal–maternal concentration ratios for the polyols also suggests that the reduction of sugars to their corresponding alcohols is favored. The role of the polyols in developing tissues is currently unknown. […]   Erythrit in Samen und Reproduktionsorganen Die biologische Bedeutung von Polyolen hat zugenommen, da man größere Mengen in Samen und Reproduktionsorganen findet [4] [5].  Erythritol Produktion beim Rind, steigt mit Fortschreiten der Trächtigkeit an und erreicht einen Peak in der Mitte der Trächtigkeit[6]. Die Bedeutung und der Fokus der Forscher auf Erythritol, gerade in der Veterinärmedizin, hat einen etwas mit einem Bakterium namens Brucella zu tun. Brucellen sind kurze, stabförmige Bakterien. Sie kommen in Geschlechtsorganen und Harntrackt von Rindern, Schafen und Schweinen vor. Sie führen, unter anderem, zu Placentitis, Frühgeburten[7] und Vergrößerung der Geschlechtsorgane. Brucellen haben eine besondere Vorliebe für Erythritol entwickelt. Mit steigender Erythritolkonzentration, steigt auch die Anfälligkeit für eine Brucelleninfektion. Das heißt jetzt nicht, dass Erythritaufnahme über die Nahrung zu einer Brucelleninfektion führt. Die metabolische Besonderheit der Geschlechtsorgane, liefern Nährstoffe, die dem Stoffwechsel von Brucella sehr entgegenkommen. So etwas nennt man auch Parasite-Host Co-Evolution. Erythritol im Serum als Indikator für Übergewicht Welche Rolle könnte Erythritol im Serum nun als Marker für Übergewicht spielen? Das ist ja die zentrale Frage. Wir wissen nun, dass die endogene Synthese von Erythritol nicht wirklich etwas Ungewöhnliches ist und sehr wohl im Menschen bereits beschrieben wurde. Erythritol ist besonders hoch konzentriert in Samen, Geschlechtsorganen, Plazenta, Nabelschnurblut und im Fötus selbst. Erythritol, und andere Polyole dürften eine Rolle in sich entwickelnden Geweben spielen. Mannose ist zum Beispiel notwendig für die Synthese von Glycoproteinen und Glycophospholipiden[8]. Die signifikant höheren Plasmalevel von Erythritol in der Gruppe, die eine deutliche Zunahme an Bauchfettmasse hatten, gegenüber der Gruppe mit stabiler Adipositas, sind interessant und könnten ein Hinweis auf Fehlregulation im PPP (Penthosephosphat Pathway) sein. Bei Übergewicht und Fettleibigkeit sehen wir oft, dass Signalwege überexpremiert werden, welche Zellwachstum, Proliferation und generell anabole Prozesse regulieren. Ähnliches könnte auch hier der Fall sein. Endogene Erythritsynthese könnte auch ein Marker für gestörte Energiegewinnung sein. Wird aus Glucose-6-Phospaht nicht Pyruvat, sondern vermehrt Erythritol synthetisiert, könnte das auch ein Hinweis auf eine gestörte Glycolyse sein. Eine andere Hypothese, die ich nicht allzu weit hergeholt finde, wäre die der Dysbiose. Wir wissen, dass Bakterien in unserem Darm eine wichtige Rolle bei der Entstehung von Übergewicht spielen. Erythritolsynthese wurde zuerst bei Bakterien beschrieben. Es wäre durchaus denkbar, dass das Erythritol im Plasma seinen eigentlichen Ursprung in bakterieller Synthese im Darmlumen hat, von dort, über eine gestörte Barrierefunktion der Darmwand, in das Blut übertritt und aus diesem Grund dort auch nachweisbar ist. Ähnliches sehen wir bei Lipopolysacchariden (LPS). LPS sind Bestandteile der Zellmembran von Gram-negativen Bakterien. Sie provozieren eine starke Immunantwort und können im Plasma nachgewiesen werden. Fazit Abschließend bleibt zu sagen, dass wir eigentlich noch nicht wirklich viel wissen. Von der Beobachtung höherer Erythritolwerte im Plasma bei Übergewichtigen, zu der Vermutung, Erythrit fördert Übergewicht – das ist schon ein sehr großer Schritt und höchst spekulativ. Ich denke aber, es ist eine spannende Beobachtung, die definitiv weiterer Forschung bedarf. Vor allem im Hinblick auf meine Alternativhypothesen was die Aktivierung von Wachstumsfaktoren, die Fehlregulation der Energiegewinnung oder sogar die bakterielle Komponente betrifft. Referenzen [1] Hiele, Martin, et al. "Metabolism of erythritol in humans: comparison with glucose and lactitol." British Journal of Nutrition 69.01 (1993): 169-176. [2] Peter D. Constable Kenneth W Hinchcliff Stanley H. Done Walter Gruenberg. Veterinary Medicine - A textbook of the diseases of cattle, horses, sheep, pigs and goats, Edition 11. October 25, 2016 Elsevier Health Sciences [3] Brusati, Valentina, et al. "Fetal and maternal non-glucose carbohydrates and polyols concentrations in normal human pregnancies at term." Pediatric research 58.4 (2005): 700-704. [4] Clark, J. B. K., et al. "D-Mannitol, erythritol and glycerol in bovine semen." Journal of reproduction and fertility 13.2 (1967): 189-197. [5] Lewin LM, Yannai Y, Melmed S, Weiss M 1982 myo-Inositol in the reproductive tract of the female rat. Int J Biochem 14:147–150 [6] Samartino, L. E., Traux, R. E., and Enright, F. M. (1994). Invasion and replication of Brucella abortus in three different trophoblastic cell lines. Zentralblatt Veterinarmedizin Reihe B. 41, 229–236. doi: 10.1111/j.1439-0450.1994.tb00223.x [7] Letesson, Jean-Jacques, et al. "Brucella Genital Tropism: What's on the Menu." Frontiers in Microbiology 8 (2017). [8] Brusati, Valentina, et al. "Fetal and maternal non-glucose carbohydrates and polyols concentrations in normal human pregnancies at term." Pediatric research 58.4 (2005): 700-704. Artikel Macht Erythrit dick? Webseiten Paleo Low Carb - JULIAS BLOG | (auf Facebook folgen) Superhumanoid - PAWELS BLOG Super | (auf Facebook folgen)

amazon pr fall mit nutrition journal android weg als labor arbeit mehr rolle macht kann invasion grund snacks bei entwicklung fokus peak cafe energie beispiel bedeutung nun schritt namen sciences menu mutter egal punkt anf markt erst unterschiede zusammenhang besonders daten aufnahme griff ergebnisse kollegen produkte gruppe mitte richtige studie sorge recherche bevor forschung metabolism samen entstehung prozesse national academy gram gruppen manche studien pediatric teilnehmer blut frontiers zucker ursprung jahrzehnte zusammenh genuss plasma perfekt hinweis daraus studenten autoren lps hinblick grunds proceedings microbiology carbohydrates die bedeutung forscher ausnahme marker zutaten nahrung glucose smoothies die arbeit interessant auftreten annahme teilnehmern skepsis serum beobachtung salat im laufe darm fetal verteilung ungew geschlechter die ergebnisse mengen bakterien british journal komponente kalorien besonderheit vorliebe veterin bestandteile goodie substanzen generell stoffwechsel reue jean jacques zunahme proliferation fructose aktivierung indikator kohlenhydrate vermutung rind enright referenzen aufschrei schafen fetts die auswahl hba1c adipositas gewichtszunahme hypothese der vorteil vergr synthese transkript energiegewinnung schweinen kohlenhydraten peter d untersucht assoziation kokosnuss naschen inositol kurzfassung bauchfett fettleibigkeit die autoren braineffect erythritol harn rindern ketose plazenta valin unterscheide bakterium nabelschnur immunantwort fortschreiten geschlechtsorgane gesundheitssch dxa die forscher metabolite wiederk geweben energielieferanten erythrit blutplasma blutproben zellmembran brucella die studenten sorbitol signalwege zellwachstum mannose wachstumsfaktoren geschlechtsorganen weitere untersuchungen darmwand nabelschnurblut leucin ketonk fettmasse metaboliten barrierefunktion polyole fehlregulation
Science and Research Show
Buildup of “Toxic Fat” Metabolite Could Explain Why Some Thin People Are Prone to Diabetes

Science and Research Show

Play Episode Listen Later Nov 9, 2016 7:13


For years, scientists have known that someone who is thin could still end up with diabetes. Yet an obese person may be surprisingly healthy. Scott Summers, Ph.D., chair of nutrition and integrative physiology, and Bhagirath Chaurasia, Ph.D., assistant professor at the University of Utah College of Health explain their new research that points to an answer to that riddle: Accumulation of a toxic class of fat metabolites, known as ceramides, may make people more prone to type 2 diabetes. Their work was recently published online in Cell Metabolism; learn more here.

Microbe Magazine Podcast
MMP010: Examining the gut microbiota of American Indians of Cheyenne and Arapaho ancestry with Cecil M. Lewis, Jr. and Krithivasan Sankaranarayanan.

Microbe Magazine Podcast

Play Episode Listen Later Mar 1, 2016 43:47


Host: Jeff Fox with special guests, Cecil M. Lewis, Jr. and Krithivasan Sankaranarayanan. Lewis and Krithivasan Sankaranarayanan—“Krithi”-- both from the University of Oklahoma in Norman talk with Jeff Fox about their analyses of the gut microbiomes of American Indians of Cheyenne and Arapaho ancestry. Lewis, Krithi, and their collaborators learned that the gut microbial taxonomic profiles of these Native Americans are characterized by a reduced abundance of anti-inflammatory bacteria and also that their fecal metabolite profiles are similar to those found in individuals with metabolic disorders. Although this was a random sampling from a generally healthy group of individuals, their gut microbiota suggests that some of them might have health problems brewing below the surface—not a surprise among a population prone to metabolic disorders such as obesity and type 2 diabetes. “For three years, we collaborated with the Cheyenne and Arapaho to discuss these topics and identify common ground for the research process, including our microbiome data," Lewis says. I don't believe the microbiome pattern resulted from the genetics of the American Indian. It is likely related to the socioeconomic challenges and resource availability in rural areas of Oklahoma." This story was featured in the February 2016 issue of Microbe Magazine. Subscribe to MMP (free) on iTunes, Stitcher, Android, RSS, or by email. You can also listen on your mobile device with the Microbeworld app. Send your microbiology questions and comments (email or audio file) to jfox@asmusa.org

JACC Podcast
Metabolite Profiles of Systolic Heart Failure

JACC Podcast

Play Episode Listen Later Jan 18, 2016 7:52


Commentary by Dr. Valentin Fuster

This Week in Microbiology
TWiM #107: The battle in your bladder

This Week in Microbiology

Play Episode Listen Later Jul 9, 2015 91:06


Hosts: Vincent Racaniello and Michael Schmidt. Vincent and Michael discuss the highly diverse microbiome of uncontacted Amerindians, and how the composition of human urine plays a role in the battle for iron. Subscribe to TWiM (free) on iTunes, via RSS feed, by email or listen on your mobile device with the Microbeworld app. Links for this episode Microbiome of uncontacted Amerindians (Sci Adv) Urinary composition controls siderocalin activity (J Biol Chem) Urine acidity and UTI susceptibility (Infect Cont Today) Image (from pdb file 3cmp) shows siderocalin (magenta) complexed with iron (orange) and enterobactin (sticks) Send your microbiology questions and comments (email or mp3 file) to twim@twiv.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twim.

RNZ: Our Changing World
We Are What We Eat - What Hair Can Tell Us

RNZ: Our Changing World

Play Episode Listen Later May 21, 2015 15:33


Metabolite biomarkers in hair may allow scientists to advise women on what they should eat to avoid pregnancy complications

RNZ: Our Changing World
We Are What We Eat - What Hair Can Tell Us

RNZ: Our Changing World

Play Episode Listen Later May 21, 2015 15:33


Metabolite biomarkers in hair may allow scientists to advise women on what they should eat to avoid pregnancy complications

MMA Roasted
Jon Jones tests positive for cocaine metabolite

MMA Roasted

Play Episode Listen Later Jan 7, 2015 7:05


Adam Hunter, Marina Shafir and Jake Ellenberger react to the news of a pre-fight test given to Jon Jones coming back positive for benzoylecgonine, a metabolite found in cocaine that can be detected in urine. Learn more about your ad choices. Visit megaphone.fm/adchoices

Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 17/19
Entwicklung, Validierung und Anwendung einer HPLC-MS/MS-Methode zur quantitativen Bestimmung von Tryptophan und seinen Metaboliten

Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 17/19

Play Episode Listen Later Oct 20, 2014


Die vorliegende Arbeit beschäftigt sich mit der Entwicklung, Validierung und Anwendung einer HPLC-MS/MS-Methode zur quantitativen Bestimmung von Tryptophan und seinen Metaboliten. Der Stoffwechsel der proteinogenen, essentiellen Aminosäure Tryptophan umfasst nicht nur den Neurotransmitter Serotonin und das in der Epiphyse gebildete Hormon Melatonin, sondern er schließt auch den Kynurenin Pathway mit ein. Die neurobiochemische Bedeutung dieses Stoffwechselweges wird bereits durch die Tatsache offensichtlich, dass im zentralen Nervensystem mehr als 95% des Tryptophans über diesen Weg metabolisiert werden. Die Intermediate des Kynurenin Pathways spielen eine bedeutende Rolle als Mediatoren zwischen Immun- und Nervensystem. Dabei nehmen sie potenziell Einfluss auf höhere zentralnervöse Funktionen, wie Kognition, Verhalten und Affekt, weshalb sie von herausragender Bedeutung für das Forschungsgebiet der Psychoneuroimmunologie sind. Auf molekularer Ebene wird Tryptophan im ersten Schritt durch die beiden Schlüsselenzyme Tryptophan-2,3-dioxygenase und Indoleamin-2,3-dioxygenase zu N-Formylkynurenin oxidiert. Durch Kynureninformidase erfolgt eine Metabolisierung von N-Formylkynurenin zu Kynurenin - der Ausgangssubstanz des gleichnamigen Stoffwechselweges. Während die Tryptophan-2,3-dioxygenase ausschließlich Tryptophan oxidiert, ist die Indolamin-2,3-dioxygenase nicht nur für den Abbau von Tryptophan spezifisch, sondern für alle Indolamine, inklusive Serotonin und Melatonin. Die Aktivität der Tryptophan-2,3-dioxygenase wird dabei durch Glucocorticoide, die der Indolamine-2,3-dioxygenase durch bestimmte Zytokine reguliert. Die Indolamin-2,3-dioxygenase spielt ebenfalls eine wichtige Rolle in der Modulation der T-Zell-Toleranz. Des Weiteren werden die Aktivitätszustände diverser Zellen des angeborenen und des erworbenen Immunsystems durch Metabolite des Kynurenins gesteuert. Einige Bestandteile des Kynurenin Pathways besitzen neuroprotektive oder neurotoxische Eigenschaften. So ist beispielsweise die neuroprotektive Kynureninsäure der bisher einzige bekannte endogene Antagonist des NMDA-Rezeptors und zusätzlich ein nichtkompetitiver Antagonist des α7-nikotinischen Acetylcholinrezeptors. Dieser Substanz steht der alternative Kynurenin-Metabolit, das exzitotoxische Neurotoxin Chinolinsäure gegenüber, welcher ein Agonist des NMDA-Rezeptors ist. Bei Untersuchungen zum Tryptophanstoffwechsel ist es daher von entscheidender Bedeutung nicht nur einzelne Substanzen sondern die Gesamtheit der Metabolite zu quantifizieren. Nur so kann die Balance zwischen neuroprotektiven und neurodegenerativen Substanzen, aber auch die Balance zwischen inhibierenden und aktivierenden Mediatoren des Immun- und Nervensystems dargestellt werden. In klinischen Studien können so Dysbalancen mit der Pathogenese einzelner Erkrankungen assoziiert werden, wodurch die Möglichkeit besteht, dass Biomarker zur frühzeitigen Diagnose identifiziert und neue Therapieansätze postuliert werden können. In dieser Arbeit wird eine neue HPLC-MS/MS-Methode vorgestellt, mit der eine bisher unerreichte Vielfalt an Tryptophan-Metaboliten quantifiziert werden kann. Die Probenvorbereitung ist eine einfache und kosteneffiziente Proteinfällung in zwei Stufen, wobei unterschiedliche Matrices, wie beispielsweise Serum oder Liquor cerebrospinalis, als Probenmaterial verwendet werden können. Um Analyte mit sehr niedrigen physiologischen Konzentrationen zu detektieren, wurde für diese eine Derivatisierung entwickelt. Die Methode benötigt ein sehr geringes Probenvolumen, ist durch die Verwendung der HPLC-MS/MS-Technologie äußerst sensitiv und spezifisch und umfasst alle bedeutenden Metabolite des Tryptophanstoffwechsels mit nur einer Probenvorbereitung. Die Robustheit wurde in einer ausführlichen Validierung bestätigt. Dabei wurden auch die analytischen Grenzwerte und Kennzahlen ermittelt, sowie die Stabilität der Proben untersucht. In Versuchen zu präanalytischen Einflüssen wurde festgestellt, dass unterschiedliche Zeitpunkte der Blutentnahme, unterschiedliche Blutentnahmesysteme und die Nahrungsaufnahme zu gravierenden Änderungen der Konzentrationen der Analyte führen. So führt die Verwendung unterschiedlicher Blutentnahmesystem beispielsweise bei der Quantifizierung des Metaboliten Picolinsäure zu Ergebnissen, die sich um bis zu 60% unterscheiden. Es wurde nachgewiesen, dass es postprandial zu starken interindividuell unterschiedlichen Änderungen der Konzentrationen einzelner Intermediate kommt. Dabei verhalten sich die freien und proteingebundenen Metabolite ebenfalls unterschiedlich. Deshalb muss für Studien eine normierte Probengewinnung mit möglichst exakten Bedingungen eingeführt werden. Auch konnte gezeigt werden, dass die Metabolisierung des Tryptophans in vivo einer circadianen Rhythmik unterliegt. Aufbauend auf diesen Erkenntnisse wurden in einem in vitro Experiment tageszeitabhängige Schwankungen nachgewiesen und der Einfluss einer LPS-Stimulation auf den Kynurenin Pathway untersucht. Durch den Einsatz dieser neuen HPLC-MS/MS-Methode besteht die Möglichkeit, die funktionellen Zusammenhänge zwischen Intermediaten des Kynurenin Pathways und diversen immunologischen, neurochemischen und anderen pathophysiologischen Vorgängen zu untersuchen. In der Literatur gibt es eine Vielzahl an Hinweisen darauf, dass der Tryptophanstoffwechsel an der Pathogenese unterschiedlichster Erkrankungen beteiligt ist. Jedoch bedarf es der genauen Klärung der Zusammenhänge und der Möglichkeit, die Gesamtheit einer potentiellen Störung des Tryptophanstoffwechsels zu erfassen. So sind im Bereich psychiatrischer und neurologischer Erkrankungen beispielsweise Schizophrenie, Alzheimer-Krankheit, Chorea Huntington und Epilepsie zu nennen. Hier wurden in publizierten Studien häufig nur einzelne Metabolite quantifiziert und isoliert betrachtet. Darüber hinaus konnten unterschiedliche Arbeitsgruppen zeigen, dass eine Aktivierung des Kynurenin Pathways auch bei der Pathogenese von Tumoren beteiligt ist, weshalb auch hier die von uns entwickelte Methode für weitere Studien von großem Nutzen ist.

Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 06/07
Zum Einfluss von experimentell induzierten katabolen, hyperglykämischen und hyperinsulinämischen Stoffwechselzuständen auf die Konzentrationsverläufe von Metaboliten des Energie- und Proteinstoffwechsels sowie von Insulin und Glucagon im Bl

Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 06/07

Play Episode Listen Later Feb 8, 2014


Die vorliegende Untersuchung an noch legeinaktiven Hennen (n=116; Lohmann Classic Brown) sollte mittels wiederholten Blutentnahmen vor, während und nach diversen tierexperimentellen Eingriffen in den Energiestoffwechsel der Hennen (jeweils n≥10) einen differenzierten Einblick in den Glucose- (und Energie-) Stoffwechsel und dessen hormonale Regulation ermöglichen. So wurden zu diesem Zweck unterschiedlich ausgeprägte katabole Stoffwechselsituationen induziert: nüchtern (16 h) mehrtägig hungernd (96 h), mehrtägig hungernd (96 h) und mittels mehrmaligen Phlorizininjektionen (0,4 g/kg LM s.c.) glucosuretisch. In einem Tagesprofil (8:00-20:00) wurde der Konzentrationsverlauf von Glucose, von Metaboliten des Fettstoffwechsels (FFS, ßHB) und des Proteinstoffwechsels (Harnsäure) sowie von Insulin und Glucagon erstellt. Ein während dieser katabolen Zustände jeweils durchgeführter i.v.-Glucosetoleranztest (0,5 g/kg LM) sollte Einblick in die jeweils vorherrschende Glucoseelimination aus dem Blut und in die dabei induzierten hyperglykämischen Auswirkungen auf die Ausschüttung von Insulin und Glucagon ermöglichen. Bei nüchternen Hennen sollte mittels i.v. Glucose-Mehrfachinjektionen (0,5 g/kg LM iv) und der dadurch für zwei Stunden anhaltend erhöhten Glucoseverfügbarkeit im Blut deren Auswirkungen auf die Konzentration der bereits genannte Metabolite und Hormone im Blut dargestellt werden. Um die Wirkung einer experimentell erhöhten Insulinverfügbarkeit im Energiestoffwechsel, und zwar unbeeinflusst von einer exogenen Glucosezufuhr, bei nüchternen und hungernden Tieren darstellen zu können, wurde Tolbutamid (20mg/kg LM) i.v. injiziert und dessen Auswirkungen auf den Konzentrationsverlauf der bereits genannten Metabolite und Hormone im Blut sowie auf die Glucoseelimination aus dem Blut im Toleranztest untersucht. Als Vergleichssituation für alle Ergebnisse bei den oben genannten tierexperimentellen Maßnahmen diente der Nüchtern-Zustand (16 h) der Hennen. Folgende Ergebnisse wurden erzielt: 4-tägiges Hungern führt im Tagesprofil zu einem tendenziellen Anstieg der Blutglucose (12,09 mmol/l bei nüchternen Tieren vs 12,95 mmol/l bei hungernden Tieren) sowie zu einer Erhöhung der Konzentrationen von Insulin (0,56 μg/l vs 1,32 μg/l) und Harnsäure (214,9 μmol/l vs 321,7 μmol/l). Der Spiegel von ßHB (1,97 mmol/l vs 2,4 mmol/l) ist nurgeringfügig höher und der Spiegel der FFS (0,775 mmol/l vs 0,605 mmol/l) ist geringfügig niedriger im Vergleich zu nüchternen Tieren, während der Glucagonspiegel (531,8 ng/l vs 510,7 ng/l) unverändert ist. Eine durch Glucosurie verschärfte viertägige Hungersituation führt zu niedrigeren Glucose- (12,23 mmol/l) und Insulinspiegeln (0,41μg/l), einem erhöhten FFS- (0,633 mmol/l) und Harnsäurespiegel (391,6 μmol/l) und einem stark erhöhten ßHB-Spiegel (6,55 mmol/l). Glucagon ist unverändert (497,3 ng/l). Offensichtlich nutzen massiv hungernde Tiere nach 4 Tagen Hungern überwiegend Fettreserven (FFS-Oxidation) als Energiequelle, wodurch der metabolische Glucoseverbrauch erheblich reduziert werden kann. Dies zusammen mit einer deutlichen Steigerung der Gluconeogenese aus Aminosäuren dürfte dazu beitragen, dass die Glucosehomeostase auf Nüchtern-Niveau gehalten werden kann. Von hormoneller Seite wird dies offensichtlich durch einen konstanten Glucagonspiegel bei gleichzeitiger Insulinresistenz gefördert. Unterstützt wird diese Vorstellung eines durch die FFSOxidation (hohe Ketogeneserate) getragenen Energiestoffwechsels und einer durch die Gluconeogenese ganz maßgeblich getragenen Glucosehomeostase durch die Ergebnisse der glucosuretisch verschärften Hungersituation. Im Glucosetoleranztest bei nüchternen Hennen zeigt sich ein schneller Anstieg der Glucose- (12,14 mmol/l auf 26,21 mmol/l) und der Insulin- (0,93 μg/l auf 4,1μg/l) Konzentration im Blut sowie ein vorübergehender Abfall von Glucagon (547,6 ng/l auf 168,9 ng/l), FFS (0,609 mmol/l auf 0,318 mmol/l) und ßHB (0,91 mmol/l auf 0,48 mmol/l). Der Harnsäurespiegel ist unverändert. 4-tägiges Hungern ebenso wie glucosuretisches Hungern verursacht eine signifikant verzögerte Glucoseelimination (T1/2 von 8,64 min auf 12,47 min bzw. 12,3 min). Die Lipolyse-hemmende Wirkung der induzierten Hyperinsulinämie, erkennbar am Abfall des FFS-Spiegel, ist bei den hungernden sowie den hungernden und glucosuretischen Tieren vermindert (52 % bzw. 59 %). Wegen der vorübergehenden i.v. erhöhten Glucoseverfügbarkeit sinkt der Spiegel von ßHB bei hungernden Tieren auf das Nüchternniveau ab (25 %). Bei glucosuretischen Tieren ist die iv-induzierte Glucoseverfügbarkeit zusätzlich belastet, so dass der stark erhöhte ßHB-Spiegel nur mäßig (58 %) gesenkt wird. Der Harnsäurespiegel lässt sich bei keinem der induzierten Stoffwechselzustände durch die Glucoseinjektion beeinflussen. Eine durch Glucose-Mehrfachinjektionen erhöhte i.v. Glucoseverfügbarkeit bei nüchternen Tieren verursacht im nachfolgenden Glucosetoleranztest ein erniedrigtes Insulinmaximum (3,11 μg/l ), aber eine nur geringgradig verzögerte Glucoseelimination aus dem Blutplasma(T1/2 8,83 min vs 8,64 min). Im Vergleich zu ausschließlich nüchternen Hennen führen wiederholte Glucosegaben zu einer Absenkung der Spiegel von ßHB und FFS. Auch der Glucagonspiegel erfährt eine deutliche Absenkung. Tolbutamid induziert ebenso wie beim Mensch auch beim Huhn eine vorübergehende Hyperinsulinämie. Auch wenn im Vergleich zum Glucosestimulus das Insulinmaximum schwächer ausgeprägt ist, wird im Hungerzustand doch ebenfaqlls eine Reduktion in der Insulinantwort sichtbar im Vergleich zu nüchternen Tieren. Die gleichzeitige Senkung des Blutzuckerspiegels ist nur mäßig (50 % des Ausgangswertes bei nüchternen Tieren, 58 % bei hungernden Tieren). Trotz der geringeren Insulinausschüttung nach Tolbutamidapplikation wird der Glucagonspiegel ähnlich wie im Glucosetoleranztest abgesenkt. Eine zusätzliche hemmende Wirkung auf die Glucagonsekretion durch Tolbutamid scheint möglich. Der Spiegel der FFS im Blutplasma nach Tolbutamidgabe wird analog zu den Ergebnissen nach Glucoseinjektion durch den jeweiligen Insulinkonzentrationsanstieg gesenkt, wobei wiederum dieser Effekt bei den hungernden Tieren geringer ausfällt. Dies zusammen mit der nur mäßigen Insulinwirkung auf den Glucosespiegel kann als weiterer Beleg für das Vorhandensein einer Insulinresistenz im Hungerzustand gewertet werden. Der Befund, dass der ßHB-Spiegel trotzt weitgehend unveränderter Glucoseverfügbarkeit nach 30 min sinkt und erniedrigt bleibt, lässt eine Hemmung der Ketogenese durch Tolbutamid möglich erscheinen. Alle Ergebnisse werden unter Einbindung des bisher publizierten Kenntnisstandes zum Energiestoffwechsel und dessen hormonaler Regulation beim Huhn diskutiert. Dabei deuten viele Fakten, auch aus der vorliegenden Untersuchung, darauf hin, dass der Stoffwechsel des Huhnes „Glucagon-getragen“ ist. So überschreiten im Blut die Spiegel von Glucagon die von Insulin oftmals deutlich, was vermuten lässt, dass Vögel normalerweise in einer katabolen, Glucose sparendenden Stoffwechselsituation leben, vergleichbar mit der bei diabetischen, hungernden oder körperlich aktiven Säugetieren. Wahrscheinlich resultiert aus dieser speziellen Stoffwechselsituation heraus der besonders hohe Normal-Blutzuckerspiegel der Vögel und gleichzeitig die Fähigkeit, auch unter diversen Belastungen des Energiehaushaltes (z.B. nüchtern, hungernd, glucosuretisch) den Glucosespiegel unverändert hoch zu halten.

This Week in Microbiology
TWiM #65: Leanness is transmissible

This Week in Microbiology

Play Episode Listen Later Oct 2, 2013 51:11


Hosts: Vincent Racaniello and Michelle Swanson. Vincent and Michelle reveal how the human gut microbiota can modulate obesity in mice. Links for this episode:  Gut microbiota modulate metabolism (Science)  Fighting obesity with bacteria (Science) Letters read on TWiM 065 Send your microbiology questions and comments (email or mp3 file) to twim@twiv.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twim.

Medizin - Open Access LMU - Teil 21/22
Effects of smoking and smoking cessation on human serum metabolite profile: results from the KORA cohort study

Medizin - Open Access LMU - Teil 21/22

Play Episode Listen Later Jan 1, 2013


Background: Metabolomics helps to identify links between environmental exposures and intermediate biomarkers of disturbed pathways. We previously reported variations in phosphatidylcholines in male smokers compared with non-smokers in a cross-sectional pilot study with a small sample size, but knowledge of the reversibility of smoking effects on metabolite profiles is limited. Here, we extend our metabolomics study with a large prospective study including female smokers and quitters. Methods: Using targeted metabolomics approach, we quantified 140 metabolite concentrations for 1,241 fasting serum samples in the population-based Cooperative Health Research in the Region of Augsburg (KORA) human cohort at two time points: baseline survey conducted between 1999 and 2001 and follow-up after seven years. Metabolite profiles were compared among groups of current smokers, former smokers and never smokers, and were further assessed for their reversibility after smoking cessation. Changes in metabolite concentrations from baseline to the follow-up were investigated in a longitudinal analysis comparing current smokers, never smokers and smoking quitters, who were current smokers at baseline but former smokers by the time of follow-up. In addition, we constructed protein-metabolite networks with smoking-related genes and metabolites. Results: We identified 21 smoking-related metabolites in the baseline investigation (18 in men and six in women, with three overlaps) enriched in amino acid and lipid pathways, which were significantly different between current smokers and never smokers. Moreover, 19 out of the 21 metabolites were found to be reversible in former smokers. In the follow-up study, 13 reversible metabolites in men were measured, of which 10 were confirmed to be reversible in male quitters. Protein-metabolite networks are proposed to explain the consistent reversibility of smoking effects on metabolites. Conclusions: We showed that smoking-related changes in human serum metabolites are reversible after smoking cessation, consistent with the known cardiovascular risk reduction. The metabolites identified may serve as potential biomarkers to evaluate the status of smoking cessation and characterize smoking-related diseases.

Question of the Week - From the Naked Scientists
Why do certain fungi produce hallucinogens?

Question of the Week - From the Naked Scientists

Play Episode Listen Later Nov 5, 2012 3:58


This week we find out why certain mushrooms contain hallucinogens, plus we ask, how long could you survive by eating your own limbs? Like this podcast? Please help us by supporting the Naked Scientists

Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 04/06
Metabolite transporters in the chloroplast envelope

Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 04/06

Play Episode Listen Later Jun 26, 2012


Tue, 26 Jun 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16185/ https://edoc.ub.uni-muenchen.de/16185/1/Jeshen_Ingrid.pdf Jeshen, Ingrid Karin ddc:570, ddc:500, Fakultät für Biologie

Medizin - Open Access LMU - Teil 19/22
Body fat free mass is associated with the serum metabolite profile in a population-based study.

Medizin - Open Access LMU - Teil 19/22

Play Episode Listen Later Jan 1, 2012


To characterise the influence of the fat free mass on the metabolite profile in serum samples from participants of the population-based KORA (Cooperative Health Research in the Region of Augsburg) S4 study. Analyses were based on metabolite profile from 965 participants of the S4 and 890 weight-stable subjects of its seven-year follow-up study (KORA F4). 190 different serum metabolites were quantified in a targeted approach including amino acids, acylcarnitines, phosphatidylcholines (PCs), sphingomyelins and hexose. Associations between metabolite concentrations and the fat free mass index (FFMI) were analysed using adjusted linear regression models. To draw conclusions on enzymatic reactions, intra-metabolite class ratios were explored. Pairwise relationships among metabolites were investigated and illustrated by means of Gaussian graphical models (GGMs). We found 339 significant associations between FFMI and various metabolites in KORA S4. Among the most prominent associations (p-values 4.75 × 10(-16)-8.95 × 10(-06)) with higher FFMI were increasing concentrations of the branched chained amino acids (BCAAs), ratios of BCAAs to glucogenic amino acids, and carnitine concentrations. For various PCs, a decrease in chain length or in saturation of the fatty acid moieties could be observed with increasing FFMI, as well as an overall shift from acyl-alkyl PCs to diacyl PCs. These findings were reproduced in KORA F4. The established GGMs supported the regression results and provided a comprehensive picture of the relationships between metabolites. In a sub-analysis, most of the discovered associations did not exist in obese subjects in contrast to non-obese subjects, possibly indicating derangements in skeletal muscle metabolism. A set of serum metabolites strongly associated with FFMI was identified and a network explaining the relationships among metabolites was established. These results offer a novel and more complete picture of the FFMI effects on serum metabolites in a data-driven network.

Medizin - Open Access LMU - Teil 19/22
On the hypothesis-free testing of metabolite ratios in genome-wide and metabolome-wide association studies

Medizin - Open Access LMU - Teil 19/22

Play Episode Listen Later Jan 1, 2012


Background: Genome-wide association studies (GWAS) with metabolic traits and metabolome-wide association studies (MWAS) with traits of biomedical relevance are powerful tools to identify the contribution of genetic, environmental and lifestyle factors to the etiology of complex diseases. Hypothesis-free testing of ratios between all possible metabolite pairs in GWAS and MWAS has proven to be an innovative approach in the discovery of new biologically meaningful associations. The p-gain statistic was introduced as an ad-hoc measure to determine whether a ratio between two metabolite concentrations carries more information than the two corresponding metabolite concentrations alone. So far, only a rule of thumb was applied to determine the significance of the p-gain. Results: Here we explore the statistical properties of the p-gain through simulation of its density and by sampling of experimental data. We derive critical values of the p-gain for different levels of correlation between metabolite pairs and show that B/(2*alpha) is a conservative critical value for the p-gain, where a is the level of significance and B the number of tested metabolite pairs. Conclusions: We show that the p-gain is a well defined measure that can be used to identify statistically significant metabolite ratios in association studies and provide a conservative significance cut-off for the p-gain for use in future association studies with metabolic traits.

Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 03/19
Einfluss verschiedener ungesättigter Fettsäuren und oxidierter Metabolite auf die Regulation der Apoptose in primären humanen Endothelzellen

Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 03/19

Play Episode Listen Later Nov 11, 2004


Thu, 11 Nov 2004 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/2878/ https://edoc.ub.uni-muenchen.de/2878/1/Vosseler_Claudia.pdf Vosseler, Claudia

Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 01/07
Untersuchung zum antioxidativen Status von Kühen und deren neugeborenen Kälbern

Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 01/07

Play Episode Listen Later Jul 23, 2004


Zusammenfassung Freie Radikale und reaktive Sauerstoffspezies, die in zahlreichen Teilprozessen des Sauerstoffmetabolismus gebildet werden, können biologische Moleküle wie Lipide, Proteine und Nukleinsäuren nachhaltig schädigen. Der Körper verfügt deshalb über eine große Vielfalt an antioxidativen Abwehrmechanismen, um eine Schädigung zu vermeiden bzw. möglichst gering zu halten. In dieser Arbeit wurde der antioxidative Status im Blut von Kälbern und deren Müttern untersucht, wobei das Hauptaugenmerk bei den Kälbern lag. Dazu wurden bei dreißig Kühen bzw. deren Kälbern Blutproben zu bestimmten Zeitpunkten peripartal bzw. von der Geburt bis zum Alter von drei Monaten genommen und auf verschiedene für die antioxidative Kapazität im Blut relevante Parameter untersucht. Die TEAC (Trolox equivalent antioxidative capacity) wurde für Kühe und Kälber als Maß für den antioxidativen Status genommen. Darüber hinaus wurden neben den Vitaminen C und E bei den Kälbern auch das Gesamteisen und die latente Eisenbindungskapazität postnatal bis zum Alter von 79 Tagen bestimmt. Zur Charakterisierung des jeweiligen Stoffwechsel- und Gesundheitsstaus der Versuchstiere wurden auch typische Metabolite (Glucose, Bilirubin), Proteine (Gesamteiweiß, Albumin) und Enzyme (ALT, AST, GLDH, CK) im peripartalen (-30 d bis 30 d) und postnatalen (0 bis 79 d) Zeitraum erfasst. Die Untersuchung der Kuh-Proben erbrachte vor der Geburt ein signifikantes Absinken der Vitamine C und E im Blutplasma. So betrug der Vitamin-Gehalt im Mittel vor der Geburt (Tag -20) 15,4±2,5 µmol/l (Vit C) bzw. 6,7±3,1 µmol/l (Vit E) und fiel bis zum Tag der Geburt signifikant auf Werte von 10,3±2,5 µmol/l (Vit C) bzw. 3,5±1,3 µmol/l (Vit E) ab. Da die TEAC-Kurve im gesamten peripartalen Zeitraum keine Schwankungen zeigte, ist beim präpartalen Absinken der Vitamin C- und Vitamin E- Konzentrationen von einem speziellen Effekt auf die Vitamine C und E auszugehen. Möglicherweise spiegelt sich hierbei der Vitamin- Abfluss über die Kolostralmilch wieder. Bei der Betrachtung der Metabolite, Proteine und Enzymaktivitäten im Serum der Kühe konnte ein für die Transitionsperiode und das Geburtsereignis typischer Verlauf dieser Parameter beobachtet werden. So herrschten z.B. hohe Glucose- bzw. Gesamtbilrubin- Spiegel am Tag der Geburt bzw. auch bis zum 5. Tag danach. Der Gesamteiweißgehalt im Serum war kurz vor und nach der Geburt undeutlich niedriger und die Enzymaktivitäten von AST und GLDH erhöhten sich tendenziell in der ersten zehn Tagen nach der Geburt. Bei der Analyse der Kälberblutproben konnte eine deutlich schlechtere Ausgangslage bezüglich des antioxidativen Status (gemessen als TEAC) nach der Geburt im Vergleich zu den Kühen festgestellt werden. Dies hatte verschiedene Gründe: Es konnte ein Einfluss des Geburtsverlaufs gezeigt werden. Demnach hatten Kälber aus Schwergeburten im Beobachtungszeitraum durchgehend im Mittel um 15,5 % erniedrigte antioxidative Kapazität, gemessen über die TEAC-Konzentration im Plasma, als Kälber aus einfacher Geburt. Außerdem war der Abfall des TEAC-Wertes bei Schwergeburtskälbern ausgehend von einem TEAC-Wert von 0,36±0,14 µmol/l (Tag der Geburt) und 0,25±0,06 mmol/l (Tag 1) sehr viel deutlicher bzw. stärker ausgeprägt als bei Kälbern aus einfacher Geburt (von 0,33±0,04 mmol/l am Tag 0 auf 0,32±0,05 mmol/l am Tag 1). Die Hypoxie, welche beim Geburtsvorgang unweigerlich auftritt, war vermutlich bei Kälbern aus Schwergeburten ausgeprägter. Die Glucose-Konzentration im Blut der Schwergeburtskälber war in den ersten Lebenstagen zum Teil signifikant höher als bei Kälbern aus einfacher Geburt. Bei den weiteren gemessenen Parametern konnten keine Unterschiede in den Geburtsgruppen beobachtet werden. Sie zeigten einen für die neonatale Periode charakteristischen Verlauf, so war zum Beispiel die Gesamtbilirun-Konzentration nach der Geburt erhöht („Hyperbilirubinämie der Neugeborenen“) und auch die CK zeigte eine deutliche Aktivitätserhöhung zu diesem Zeitpunkt. Um den Einfluss abzuschätzen, den der Abbau des fetalen Hämoglobins auf den antioxidativen Status der Kälber hat, wurden die latente Eisenbindungskapazität, freies Eisen und das Gesamteisen im Serum der Kälber bestimmt. Mit der verwendeten Analysemethode konnte kein freies Eisen nachgewiesen werden. Die latente Eisenbindungskapazität verdreifachte sich vom Tag der Geburt (7,6±2,8 µmol/l) bis zum elften Lebenstag (20±4,4 µmol/l) und sank dann wieder auf das Niveau von 15,4±5,2 µmol/l (Tag 49) ab. Die geringen LEBK-Werte kurz nach der Geburt sind vermutlich auf die freien Eisenionen, die beim Abbau des fetalen Hämoglobins freiwerden, zurückzuführen. Die Konzentration des Gesamteisens im Serum zeigte erwartungsgemäß einen gegensätzlichen Verlauf, und sank nach der Geburt auf 60% des Ausgangswertes (16,4±6,7 µmol/l am tag 0) ab, um dann ab dem fünften Lebenstag kontinuierlich bis zum Ende des Untersuchungszeitraumes auf 26,5±3,2 µmol/l (Tag 79) anzusteigen. Es wurden die TEAC-Werte von kranken und gesunden Kälbern gegenüber gestellt. Dabei konnten keine Unterschiede im Niveau und im Verlauf der TEAC-Kurven nachgewiesen werden. Bei der geringen Anzahl an kranken Tieren (nur sechs Kälber) in dieser Untersuchung stellte sich die TEAC nicht als deutlicher prognostischer Faktor hinsichtlich der Morbidität heraus. Um eine endgültige Aussage darüber zu treffen, muss eine größere Tierzahl untersucht werden.

Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 02/19

Vergleich verschiedener Enzymimmunoassays zur Detektion von Drogen oder deren Metabolite im menschlichen Urin. Getestet wurden dabei vor allem die Systeme DRI und Emit II im Vergleich zum CEDIA Immunoassay.

Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 01/19
Untersuchung zur Pathophysiologie der experimentellen Pneumokokkenmeningitis an der Ratte

Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 01/19

Play Episode Listen Later Nov 14, 2002


Zusammenfassung Trotz beträchtlicher Fortschritte in der antibiotischen Behandlung bakterieller Erkrankungen blieb der Krankheitsverlauf und die Sterberate der bakteriellen Meningitis, insbesondere der Pneumokokkenmeningitis, innerhalb der letzten Jahre unverändert. Mit der Erkenntnis, daß das Ausmaß der intrakraniellen Entzündung positiv mit dem Verlauf der Erkrankung korreliert, gewann die Frage nach der Rolle der Leukozyten im Rahmen des Krankheitsgeschehens zunehmend an Bedeutung. Das Ziel der vorliegenden Arbeit war daher, die Bedeutung von Granulozyten, Monozyten und des Zusammenspiels dieser beiden Zellarten im Rahmen der pathophysiologischen Abläufe während der experimentellen Pneumokokkenmeningitis aufzudecken. Insbesondere wurden Veränderungen in den Parametern intrakranieller Druck, Liquorpleozytose und Blut-Hirnschrankenstörung in der Frühphase und im fortgeschrittenen Stadium der Meningitis untersucht. Hierfür kamen zwei Tiermodelle zur Anwendung: 1) Frühphase der Erkrankung: Hierbei wurde narkotisierten Ratten durch intrazisternale Injektion von Hitze-abgetöteten Pneumokokken (HKP) eine Meningitis induziert. Anschließend wurden über einen Zeitraum von sechs Stunden kontinuierlich Blutdruck, intrakranieller Druck und Temperatur überwacht. Eine Stunde vor Versuchsende erhielten die Tiere 1 ml Evans-blau zur Quantifizierung der Blut-Hirnschrankenstörung intravenös injiziert. Nach Ablauf des Beobachtungszeitraums wurden Liquorproben zur Bestimmung der Zellzahl und Evans-blau-Konzentration und Gehirnproben zur histologischen Aufarbeitung gewonnen. 2) Fortgeschrittenes Stadium der Erkrankung (Spätphase): In diesem Modell wurde die Meningitis mittels transkutaner Injektion von Streptococcus pneumoniae Serotyp 3 in die Cisterna magna ausgelöst. 24 Stunden nach Injektion wurden auch bei diesen Tieren die Leukozytenzahl und Evans-blau Konzentration im Liquor bestimmt sowie Gehirnproben zur weiteren Aufarbeitung gewonnen. Um die Beteiligung der Granulozyten an den pathophysiologischen Veränderungen während der Früh- bzw. Spätphase der bakteriellen Meningitis untersuchen zu können, wurden die Versuchstiere mit einem gegen polymorphkernige Leukozyten gerichteten Antikörper (Rabbit Anti-Rat-PMN-Antikörper) vorbehandelt, wodurch eine nahezu vollständige Depletion der Granulozyten erreicht wurde. Um ebenso die durch Monozyten bedingten Auswirkungen während der Frühphase der Pneumokokkenmeningitis feststellen zu können, wurde eine weitere Gruppe mit λ-Carrageenan vorbehandelt, einer Substanz, deren toxische Wirkung auf mononukleäre Zellen bekannt ist. In einer dritten Gruppe schließlich wurden beide Wirkstoffe in Kombination miteinander verabreicht. Für die Frühphase der Pneumokokkenmeningitis ergaben sich folgende Ergebnisse: 1) Die intrazisternale Gabe von Hitze-abgetöteten Pneumokokken führte im Verlauf von sechs Stunden bei den Ratten zu einem Anstieg des intrakraniellen Drucks, der Liquorleukozytenzahl und zur Störung der Blut-Hirnschrankenfunktion. 2) Die Depletion neutrophiler oder monozytärer Zellen bewirkte bei den Versuchstieren eine signifikante Reduktion der Liquorpleozytose und des intrakraniellen Druckanstieges. Gemessen an der Evans-blau-Extravasation wiesen diese Tiere auch eine geringere Funktionsstörung der Blut-Hirnschranke auf. 3) Bei den zweifach-depletierten Tieren waren diese Ergebnisse noch ausgeprägter. Sie zeigten bzgl. des intrakraniellen Druckanstieges, der Liquorpleozytose und Blut-Hirnschrankenfunktion keinen wesentlichen Unterschied zu unbehandelten Kontrolltieren. Für das fortgeschrittene Stadium der Meningitis zeigte sich folgendes: Nach Depletion granulozytärer Zellen ließ sich auch hier eine deutliche Reduktion des intrakraniellen Druckanstieges, der Liquorpleozytose und der Blut-Hirnschrankenstörung erreichen. Allerdings war diese Reduktion weitaus schwächer ausgeprägt als in den vorangegangenen Untersuchungen. Derzeit liegen noch keine Langzeituntersuchungen zur Wirkdauer des gegen polymorphkernige Leukozyten gerichteten Antikörpers vor. Daher ist nur zu vermuten, daß möglicherweise ein zunehmender Wirkverlust des Antikörpers während des Experiments für diese Diskrepanz verantwortlich sein könnte. Unterstützung findet diese Annahme durch den eindeutig höheren prozentualen Anteil neutrophiler Zellen in Differentialblutbildern von Langzeitversuchen verglichen mit denjenigen der Kurzzeitversuche. Da mit Carrageenan vorbehandelte Tiere zum Teil erhebliche Blutdrucksenkungen im Laufe des Experimentes aufwiesen, war es nicht möglich, diese Substanz in den Langzeitversuchen einzusetzen. Zusammenfassend konnte mit dieser Arbeit gezeigt werden, daß Granulozyten, aber auch Monozyten eine essentielle Rolle im Hinblick auf die Ursachen pathophysiologischer Veränderungen während der Früh- und vermutlich auch der späteren Phase der Pneumokokkenmeningitis spielen. Andere Methoden zur Depletion monozytärer Zellen sollten künftig angewendet werden, um die Auswirkungen einer Monozyten-Depletion auf die fortgeschrittene Phase der Pneumokokkenmeningitis genauer untersuchen zu können. Es kommen verschiedene Mechanismen in Betracht, wie Granulozyten und Monozyten zu diesen Veränderungen führen können: 1) Neutrophile sind als Produzenten gewebezerstörender Faktoren bekannt. Ihr Waffenarsenal umfaßt eine Vielzahl toxischer Metabolite, darunter freie Sauerstoffradikale, Stickstoffmonoxid und Enzyme wie Matrix-Metalloproteinasen. In vorangegangenen Studien wurde bereits die Relevanz dieser Mediatoren für die bakterielle Meningitis belegt (z.B. Pfister et al., 1990 a,b; Koedel et al., 1995; Paul et al., 1998). Ohne Mithilfe anderer Mitglieder des Immunsystems sind Neutrophile nicht fähig zwischen fremden und wirtseigenen Antigenen zu unterscheiden; ihre „Waffen“ richten sich in diesem Fall auch gegen den eigenen Wirt. Frühere Studien zeigten, daß im Liquorraum von einem Komplementmangel ausgegangen werden muß und somit hier der zellulären Abwehr die nötige Unterstützung fehlt, um das richtige Ziel der Zerstörung preiszugeben. 2) Monozyten/Makrophagen gelten als Hauptproduzenten von IL-1 und anderen Chemokinen, die als chemotaktisches Signal für Neutrophile dienen. Sie stellen damit unverzichtbare Komplizen und Vorläufer für granulozytäre Zellen dar, da sie wesentlich an deren Immigration in den Subarachnoidalraum beteiligt sind. Ferner könnten mononukleäre Zellen durch ihre Freisetzung von Glutamat direkt an den auftretenden Schäden beteiligt sein.

Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 01/19

Der isolierte 3-Methylcrotonyl-CoA: Carboxylase (MCC) Mangel ist eine angeborene Störung im Abbau der Aminosäure Leucin. Es sind sowohl bis ins Erwachsenenalter asymptomatische als auch frühe letale Verläufe beschrieben. Die Ursachen des variablen Phänotyps sind nicht verstanden. Das Enzym ist zusammengesetzt aus α- und β - Untereinheiten. Die kodierenden humanen Gene MCCA und MCCB wurden kürzlich in unserer Arbeitsgruppe kloniert. Die Erweiterung des Neugeborenen-Screenings mittels Tandem-Massenspektrometrie in Bayern erbrachte die überraschende Erkenntnis, daß der MCC Mangel wahrscheinlich die häufigste organische Azidämie (etwa 1 : 40 000) darstellt und asymptomatische Mutationsträger existieren. Über Risiko und Prognose dieser metabolischen Störung ist derzeit noch keine Aussage möglich. In dieser Arbeit sollte daher eine Methode zur molekulargenetischen Charakterisierung von Patienten mit MCC Mangel etabliert werden, um den prognostischen Wert des Genotyps studieren und damit die Beratung und Betreuung der betroffenen Familien verbessern zu können. Es wurden 3 asymptomatische Patienten aus dem Neugeborenenscreening sowie ein Patient, der mit cerebralen Krampfanfällen aufgefallen war, untersucht. Die Diagnose war bei allen Patienten durch Bestimmung der typischen Metabolite in Urin (3-Hydroxyisovaleriansäure und 3- Methylcrotonylglycin) und Blut (3-Hydroxyisovaleryl-Carnitin) gestellt worden. Für die molekulargenetische Diagnostik des MCC Mangels wurde die Mutationsanalyse auf genomischer und cDNA Ebene für MCCA und MCCB etabliert. Es wurden zwei Patienten mit veränderten Allelen im MCCA- und zwei Patienten mit Mutationen im MCCB-Gen identifiziert. Ein Patient war compound-heterozygot für die Missense-Mutation S535F (1604C>T) und die Nonsense-Mutation V694X (2079delA) im MCCA Gen. Bei einem zweiten Patienten wurde S535F (1604C>T) heterozygot nachgewiesen. Ein Patient mit konsanguinen Eltern war homozygot für die Missense-Mutation S535F (1604C>T). Ein weiterer wies die Missense-Mutation E99Q (295G>C, cDNA: homozygot; gDNA: heterozygot) mit einen Allelverlust auf. In zwei Fällen werden zusätzliche Mutationen in der Promotorregion bzw. in einem Intron angenommen. Für alle gefundenen Mutationen kann von phänotypischer Relevanz ausgegangen werden. Drei davon waren bisher unbekannt und wurden von uns erstbeschrieben. Unsere Ergebnisse bestätigen die Rolle von MCCA und MCCB azielführende Methode zur molekulargenetischen Charkterisierung von Patienten mit MCC Mangel dar und bildet damit die Grundlage für Expressionsstudien und Studien zur Untersuchung der Genotyp-Phänotypkorrelation.ls humane Krankheitsgene. Die hier etablierte Mutationsanalyse stellt eine

Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 01/06
Expressionsprofile von ABC-Transportern in Arabidopsis thaliana

Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 01/06

Play Episode Listen Later Mar 15, 2002


Die Superfamilie der ABC-Proteine ist eine der größten bisher bekannten Proteinfamilien. Ihre Mitglieder enthalten ein oder zwei nukleotidbindende Domänen mit je einem Walker A- und B-Motiv, sowie das charakteristische ABC-Motiv. Ein Großteil darunter sind Membranproteine, die zusätzlich ein oder zwei Transmembrandomänen besitzen. Diese ABC-Transporter sind vor allem in Mensch und Hefe charakterisiert, wo sie in zahlreichen Transportprozessen über die Membranen involviert sind. Über die Funktion der ABC-Transporter in pflanzlichen Organismen ist wenig bekannt, jedoch gibt es Hinweise dass diese Proteinfamilie in Pflanzen auch an der Kompartimentierung von Fremdstoffmetaboliten beteiligt ist. In der Modellpflanze Arabidopsis thaliana wurden 103 ABC-Transportergene annotiert, die sich in 9 Subfamilien aufteilen. Experimentell nachgewiesen wurden bisher lediglich 6 Mitglieder aus 2 Subfamilien. In dieser Arbeit wurden 28 ABC-Transporter aus 6 Subfamilien, davon 4 bisher nicht untersuchte, hinsichtlich organspezifischer Expression und Induktionsverhalten nach Herbizid- bzw. Safenerbehandlung untersucht. Dazu wurde ein DNA-Array ("Detox-Array") mit genspezifischen Sonden zur parallelen Transkriptanalyse etabliert. Zusätzlich wurden in Zusammenarbeit mit anderen Projekten weitere Genfamilien mit einbezogen, die potenziell an der Detoxifizierung von Xenobiotika beteiligt sind (Cytochrom P450 Monooxygenasen, Glutathion-S-Transferasen und UDP-Glycosyltransferasen), um Koregulationen einzelner Mitglieder der unterschiedlichen Genfamilien untersuchen zu können. Um die Unterscheidung auch hoch homologer Mitglieder dieser Familien zu ermöglichen, wurden Sonden aus dem 3‘-untranslatierten Bereich dieser Gene entwickelt und auf ihre Eignung zur Transkriptmessung untersucht. Die Expressionsanalyse der ABC-Transporter in Wurzeln, Stängeln, Blättern, Blütenständen und Schoten zeigte neben den sechs bereits bekannten ABC-Transportern Transkripte von 21 weiteren Vertretern. Die meisten waren in der Wurzel (26 von 28) nachzuweisen, die wenigsten (7 von 28) im Blatt. Am höchsten exprimiert waren AtMRP12 und AtPDR8 in der Wurzel und AtMRP5 in der Schote. Die Induktion der ABC-Transporter durch Xenobiotika wurde an Pflanzen 24h oder 36h nach Behandlung mit unterschiedlichen Chemikalien (Primisulfuron, Bromoxynil, Benoxacor) in sublethalen Dosen untersucht. Für die beiden Herbizide typische Schäden konnten erst 3 Tage nach der Behandlung beobachtet werden. Neben der in der Literatur beschriebenen Primisulfuron-Induktion von AtMRP3 (Tommasini et al., 1997) waren AtPDR8, AtMRP5, AtMRP4 und AtAOH1 transient nach 24h induziert. Mit einem Antiserum, das gegen die Subfamilie der PDR-Transporter erzeugt worden war, konnte deren Induktion durch Primisulfuron und Benoxacor auch auf Proteinebene nachgewiesen werden. Eine spezifische 6-fache Induktion nach Bromoxynil-Behandlung zeigte der ABC-Transporter AtTAP1. Die sechs genannten ABC-Transporter stellen somit Kandidaten dar, die an der Kompartimentierung von Metaboliten beteiligt sein können. Dabei kann es sich entweder um Primisulfuron- bzw. Bromoxynilmetabolite oder durch die Behandlung mit den Xenobiotika entstandene endogene Metabolite handeln. Eine Hauptkomponentenanalyse der Expressionsprofile zeigte, dass auf der Basis der auf dem Detox-Array vertretenen, aus dem Entgiftungs- und Sekundärmetabolismus ausgewählten Genfamilien eine eindeutige Unterscheidung der Antwort auf die verschiedenen Herbizide abgeleitet werden kann. Weitere Daten aus Kollaborationen mit anderen Projekten wurden in einer zweiten Hauptkomponentenanalyse mit einbezogen und zeigen, dass die Unterschiede vor allem auf die sekundären Auswirkungen der Herbizide zurückzuführen sind. Die dabei gefundene Koregulation der Primisulfuron-Behandlung mit der Reaktion auf das Signalmolekül Salicylsäure und ein bakterielles Pathogen ließ weiter schließen, dass Primisulfuron einen Elicitor-ähnlichen Effekt auf die Pflanze hat. Zur weiterführenden Funktionsanalyse von ABC-Transportern wurden parallel zu diesen Arbeiten knock-out Mutanten gesucht. In einer Kollektion des MPI für Züchtungsforschung in Köln konnten zwei Mutanten identifiziert werden, die jeweils ein En-Transposon innerhalb der offenen Leserahmen von AtPDR4 bzw. AtMDR4 besitzen.

Biologie - Open Access LMU - Teil 01/02
Metabolite-mediated catalyst conversion of PFK and PFP. a mechanism of enyme regulation in green plants

Biologie - Open Access LMU - Teil 01/02

Play Episode Listen Later Jan 1, 1984


Metabolites known to occur in the cytosol of photosynthetic leaf cells were found to mediate the reversible conversion of pyrophosphate—D-fructose-6-phosphate 1-phosphotransferase (PFP) to phosphofructokinase (PFK) in partially purified preparations from spinach leaves. Preincubation of PFP with fructose 2,6-bisphosphate, ATP or fructose 6-phosphate converted PFP to PFK. The reverse reaction (PFK → PFP) was promoted by UDP-glucose plus pyrophosphate. These conversions in catalytic capability were accompanied by changes in molecular mass and charge. The results are in accord with the view that the alterations in PFP and PFK activity, provisionally called ‘metabolite-mediated catalyst conversion’, represent a regulatory mechanism to direct left cytosolic carbon flux in either the biosynthetic or degradatory direction.