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dr. frankenstein

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  1. dr. frankenstein

    Sublimation, culture, and creativity.

    . Psychoanalysis? Is That Still Around? .
  2. . ...well, I did not know where to post this remembering endless discussions on the role of satellite cells in hypertrophy at mindandmuscle.net Starring or Supporting Role? Satellite Cells and Skeletal Muscle Fiber Size Regulation https://www.physiology.org/doi/abs/10.1152/physiol.00019.2017?fbclid=IwAR2G09SBA2IneSSynQzuuFQ3ZXHJDb0h4ufoHEFEodm5cpLo3Ig4g7bk_18&journalCode=physiologyonline "INCREASED baseline SATELLITE CELL density in adult mice DOES NOT result in LARGER muscle fibers, indicating that satellite cells themselves DO NOT DRIVE ADULT MUSCLE FIBER GROWTH" then, what drives hypertrophy ?? increase in cytoplasmic volume and nucleus growth ....not more myonuclei Turn Up the Volume: Uncovering Nucleus Size Control Mechanisms https://www.physiology.org/doi/abs/10.1152/physiol.00019.2017?fbclid=IwAR2G09SBA2IneSSynQzuuFQ3ZXHJDb0h4ufoHEFEodm5cpLo3Ig4g7bk_18&journalCode=physiologyonline "nucleus growth is regulated by the volume of cytoplasm in the immediate vicinity of the nucleus...the authors demonstrated that cytoplasmic volume is sufficient to increase nucleus growth". .
  3. . for ultra anaerobic purposes ? If serotonin does not exhaust you, it makes you stronger https://sci-hub.tw/https://doi.org/10.1113/JP277317 The SSRI intake resulted in a stronger force produced during a single maximal voluntary contraction. However, during repeated maximal voluntary contractions, the force produced and the time to exhaustion were reduced compared to individuals who ingested a placebo. To figure out if the fatigue observed in subjects who took paroxetine had a central or a peripheral origin, the authors used the superimposed twitch method. This technique consists in measuring the extra force produced by an electric chock applied on the motor nerve during maximal voluntary contractions. The amplitude of the superimposed twitch reflects the inability of the central nervous system to activate the muscle. Before fatiguing contractions, the superimposed twitch was smaller for subjects who took paroxetine. However, it became bigger after repeated maximal voluntary contraction. Since paroxetine did not change the contractile properties of the muscle, the authors concluded that the supplement of fatigue occurring after SSRI intake was purely central. .
  4. dr. frankenstein

    Testosterone Prevents Hairloss?

    . Topical JAK inhibitors .
  5. dr. frankenstein

    New Member. Amphetamine Neurotoxicity & Rehab

    posted sometime ago Direct and Systemic Administration of a CNS-Permeant Tamoxifen Analog Reduces Amphetamine-Induced Dopamine Release and Reinforcing Effects https://www.nature.com/npp/journal/v42/n10/full/npp201795a.html Amphetamines (AMPHs) are globally abused. With no effective treatment for AMPH addiction to date, there is urgent need for the identification of druggable targets that mediate the reinforcing action of this stimulant class. AMPH-stimulated dopamine efflux is modulated by protein kinase C (PKC) activation. Inhibition of PKC reduces AMPH-stimulated dopamine efflux and locomotor activity. The only known CNS-permeant PKC inhibitor is the selective estrogen receptor modulator tamoxifen. In this study, we demonstrate that a tamoxifen analog, 6c, which more potently inhibits PKC than tamoxifen but lacks affinity for the estrogen receptor, reduces AMPH-stimulated increases in extracellular dopamine and reinforcement-related behavior. In rat striatal synaptosomes, 6c was almost fivefold more potent at inhibiting AMPH-stimulated dopamine efflux than [3H]dopamine uptake through the dopamine transporter (DAT). The compound did not compete with [3H]WIN 35,428 binding or affect surface DAT levels. Using microdialysis, direct accumbal administration of 1 μM 6c reduced dopamine overflow in freely moving rats. Using LC-MS, we demonstrate that 6c is CNS-permeant. Systemic treatment of rats with 6 mg/kg 6c either simultaneously or 18 h prior to systemic AMPH administration reduced both AMPH-stimulated dopamine overflow and AMPH-induced locomotor effects. Finally, 18 h pretreatment of rats with 6 mg/kg 6c s.c. reduces AMPH-self administration but not food self-administration. These results demonstrate the utility of tamoxifen analogs in reducing AMPH effects on dopamine and reinforcement-related behaviors and suggest a new avenue of development for therapeutics to reduce AMPH abuse.
  6. dr. frankenstein

    Nandrolone and Stanozolol can be directly estrogenic/progestagenic

    . Why the binding of androgens to ERs Determinants of Ligand Specificity of Estrogen Receptor-α: Estrogen versusAndrogen Discrimination http://www.jbc.org/content/273/2/693.long We have been interested in understanding how the estrogen receptor (ER) binds estrogens and discriminates between different classes of steroids with closely related structures. Using insights from our prior studies on ER and from sequence comparisons of steroid receptors, we identified three residues in the hormone-binding domain of the human ER, Leu345, Thr347, and Glu353, that we considered were likely to be involved in steroid A-ring recognition and therefore estrogen versusandrogen discrimination. We then tested the effect on ER activity of mutating these ER residues to the corresponding androgen receptor residues. Specifically, we examined the ability of the mutant receptors to bind and be activated by 17β-estradiol and three different androgens. No change in receptor activity was observed with the T347N mutation, while the L345S mutation greatly reduced ER activity in response to all ligands. Interestingly, the E353Q substitution behaved as expected, causing a 9-fold reduction in the transactivation potency of estradiol and a concomitant 10–140-fold increase in the transactivation potency of different androgens. These reciprocal changes in the transcriptional effectiveness of estrogens and androgens correlated with a decreased affinity of the E353Q ER for estradiol binding and an increased affinity for androgen binding. Therefore, amino acid Glu353 appears to be playing a significant role in binding the A-ring phenolic group of estradiol and in receptor discrimination between estrogens and the most closely structurally related steroids, androgens. Directed Evolution of Human Estrogen Receptor Variants with Significantly Enhanced Androgen Specificity and Affinity http://www.jbc.org/content/279/32/33855.long Human estrogen receptor α (hERα) and human androgen receptor exhibit exquisite ligand specificity, which underlies their remarkable ability to effect ligand-regulated gene transcription in a highly distinctive and specific manner. Here we used a directed evolution approach to create hERα variants with enhanced androgen specificity and affinity with the goal to better understand the molecular basis of ER ligand specificity and the evolutionary mechanism of nuclear receptors. We developed a sensitive yeast two-hybrid system to screen for hERα variants with increased transactivation potency toward testosterone. After two rounds of directed evolution, we identified five hERα variants with dramatically improved transactivation potency toward testosterone in both yeast and mammalian cells. These variants showed up to 7,600-fold improvement in the binding affinity for testosterone and only slightly reduced affinity toward 17β-estradiol. Detailed analysis of these evolved variants and a few site-directed mutants generated de novo led to several unexpected findings including the following. 1) Only two beneficial mutations were needed to create hERα variants with near nanomolar affinity for testosterone. 2) Some beneficial mutations were synergistic, context-dependent, or non-additive. 3) Of the five identified beneficial mutations, four of them were not in the ER ligand binding pocket and yet exerted important action on ligand specificity. 4) The single ligand-contacting mutation E353Q plays a dominant role in discriminating androgens and estrogens. These results, viewed in conjunction with the ligand exploitation model of nuclear receptor evolution, suggest that the mutation E353Q may represent a key event in the evolution of androgen receptors from an ancestral estrogen receptor and that ligand promiscuity may play an important role in the creation of new nuclear receptors via divergent evolution. .
  7. dr. frankenstein

    Nandrolone and Stanozolol can be directly estrogenic/progestagenic

    . Blocks Glucocorticoids Receptors https://www.vin.com/apputil/content/defaultadv1.aspx?id=3846454&pid=11147& ...stanozolol shows a higher affinity for the glucocorticoid receptors than for those of the androgens. The glucocorticoid receptor block is carried out for low Stanozolol doses and it reduces the tissue catabolic activity... .
  8. dr. frankenstein

    A Cure for Obesity?

    . ....maybe the inverse Lilly's diabetes drug data impresses, hurts rival Novo's shares https://www.reuters.com/article/us-lilly-study/lillys-diabetes-drug-data-impresses-hurts-rival-novos-shares-idUSKCN1ME11Z The novel drug targets two key gut hormones at the same time, and could pose a threat to currently available single-hormone drugs, which form a large and growing part of Novo’s business. Lilly’s treatment reduced blood sugar levels in type 2 diabetes patients by up to 2.4 percent and produced an average weight reduction of up to 12.7 percent in a mid-stage study by targeting the GLP-1 and GIP hormones. The trial results set a new industry gold standard versus marketed GLP-1s, including Novo’s Ozempic for both blood sugar lowering and weight loss, Citi analyst Andrew Baum said. Lilly’s shares were rose 6.5 percent to a record high of $115.68 in early trading, while those of Novo fell nearly 8 percent. .
  9. dr. frankenstein

    fasted or not ?

    . ...it depends Pre-Exercise Breakfast Ingestion versus Extended Overnight Fasting Increases Postprandial Glucose Flux after Exercise in Healthy Men https://www.physiology.org/doi/abs/10.1152/ajpendo.00163.2018 To characterize postprandial glucose flux after exercise in the fed versus overnight fasted-state and to investigate potential underlying mechanisms. Methods: In a randomized order, twelve men underwent breakfast-rest (BR; 3 h semi-recumbent), breakfast-exercise (BE; 2 h semi-recumbent before 60-min of cycling (50% peak power output) and overnight fasted-exercise (FE; as per BE omitting breakfast) trials. An oral glucose tolerance test (OGTT) was completed post-exercise (post-rest on BR). Dual stable isotope tracers ([U-13C] glucose ingestion and [6,6-2H2] glucose infusion) and muscle biopsies were combined to assess postprandial plasma glucose kinetics and intramuscular signaling, respectively. Plasma intestinal fatty acid binding (I-FABP) concentrations were determined as a marker of intestinal damage. Results: Breakfast before exercise increased post-exercise plasma glucose disposal rates during the OGTT, from 44 g•120 min-1 in FE [35 to 53 g•120 min-1] (mean [normalized 95% CI]) to 73 g•120 min-1 in BE [55 to 90 g•120 min-1; p = 0.01]. This higher plasma glucose disposal rate was, however, offset by increased plasma glucose appearance rates (principally OGTT-derived), resulting in a glycemic response that did not differ between BE and FE (p = 0.11). Plasma I-FABP concentrations during exercise were 264 pg•mL-1 [196 to 332 pg•mL-1] lower in BE versus FE (p = 0.01). Conclusion: Breakfast before exercise increases post-exercise postprandial plasma glucose disposal, which is offset (primarily) by increased appearance rates of orally-ingested glucose. Therefore, metabolic responses to fed-state exercise cannot be readily inferred from studies conducted in a fasted state. Is eating breakfast good for you ? https://www.newsweek.com/eating-breakfast-good-you-meal-primes-body-burn-more-carbs-1073128 Researchers at the University of Bath, University of Birmingham, Newcastle University and the University of Sterling worked together on the paper published in the American Journal of Physiology: Endocrinology and Metabolism. Dr. Javier Gonzalez, co-author of the study and senior lecturer in the Department of Health at the University of Bath, told Newsweek: "We were surprised to see how the breakfast altered muscle metabolism during and after exercise, the extra carbohydrate burned during exercise after breakfast wasn’t just the carbohydrate from the breakfast but also extra carbohydrate burning from the carbohydrate (glycogen) stores in our muscle.” Switching between occasionally performing exercise before breakfast and performing exercise after breakfast might be beneficial when it comes to optimizing how our bodies use fuel, according to Dr. Gonzalez. “With increased carbohydrate burning during exercise, there is less fat being burned. This may not be desirable under certain conditions, and therefore the guidance to eat breakfast before or after exercise would depend on what the individual would like to achieve.” ------- The results follow a 2016 study carried out by scientists at the University of Surrey, U.K., which investigated how timing meals around exercise could help a person burn fat. The team concluded women should eat 90 minutes before exercise to burn fat, and to avoid consuming carbohydrates immediately after working out. Men, meanwhile, should eat 90 minutes after exercise if they want to burn fat. https://www.surrey.ac.uk/features/research-surrey-suggests-timing-your-exercise-and-meals-can-lead-weight-loss While all the women ended up burning slightly more fat at the end of the experiment, those who were consuming carbohydrates before their exercise were burning more. Meanwhile, all the men were actually burning slightly less fat at the end of the experiment, but those who were consuming carbohydrates after their exercise were better off. There were no significant differences in their weights or waist circumference, but their blood sugar levels changed in the same way as their fat burning. It’s evident that men and women burn fat and carbohydrates in different ways. Men are ‘carbohydrate burners’ – if as a man you eat carbohydrates then your body is going to burn it rather than fat. However, given that we all have to eat, it is better for men to eat after exercising if they want to burn fat. This is because, after exercise, men will use that carbohydrate to replace the carbohydrate in their muscles rather than burn it for fuel and will continue to burn fat instead. For women, the results show that eating before they exercise is better than eating after if they want to burn fat. Women’s bodies tend to burn fat more easily than men’s, and are not fuelled so much by carbohydrates. Moreover, women are much better at conserving carbohydrates during exercise. So when women eat carbohydrates soon after exercise, this is effectively overloading them with fuel, and interferes with the body’s ability to burn fat. Top tips For women, eating about 90 minutes before exercise is better than eating after if they want to burn fat The key message for women is: don’t eat carbohydrates immediately after your exercise. You don’t have to eat before, just be mindful of what you eat after It is better for men to eat around 90 minutes after exercise if they want to burn fat .
  10. dr. frankenstein

    Nandrolone and Stanozolol can be directly estrogenic/progestagenic

    . . a very interesting article about AASs binding albeit a theoretical article, it reproduces various experimental findings. stanozolol a tripetiae steroid ?? Synthetic anabolic steroids binding to the human androgen receptor http://www.nipne.ro/rjp/2015_60_7-8/RomJPhys.60.p1112.pdf Within this study we assess the affinity binding of a few synthetic anabolic oral administrable steroids: oxymetholone, oxandrolone, methandrostenolone and stanozolol to the human androgen receptor (hARLBD) and a few nonspecific receptors. Molecular docking studies reveal that all these steroids are able to bind to the hARLBD and other nuclear and hormone receptors, despite the law sequence similarity between these receptors. The highest binding energy is registered for methandrostenolone binding to hARLBD, its molecular properties being the most similar to those of the natural ligand, testosterone. Stanozolol provides higher interaction energies for nonspecific receptors in comparison to its interaction with hARLBD. Four oral administrable synthetic anabolic steroids are considered in this study: oxymetholone (OXY), oxandrolone (OXA), methandrostenolone (MAS) and stanozolol (STA). interesting thing, can bind to thyroid receptor (less fat ?) binding domains of such possible nonspecific receptors: 1UOM for human estrogen receptor, 2BAW for human nuclear receptor, 2PIN for thyroid receptor and 3L0J for orphan nuclear receptor. We assessed the interactions of considered anabolic steroids with these targets and the results are presented in Table 4. All considered anabolic steroids are able to bind to these targets, some predicted interactions being stronger than their interaction with the human androgen receptor binding domain. The results obtained within this study indicate that synthetic anabolic steroids are able to bind to the active site of hARLBD and also to another human nuclear and hormone receptors. Among the synthetic anabolic steroids, the methandrostenolone possesses the highest binding affinity for hARLBD. Moreover, its molecular properties are the most similar to those of testosterone and this outcome illustrates that even small differences in the ligand properties significantly influences the interaction strength. For the nonspecific interactions, stanozolol possesses the highest binding energies for almost all the nonspecific targets, these energies being even higher than its interaction energy with hARLBD. . .
  11. dr. frankenstein

    Nandrolone and Stanozolol can be directly estrogenic/progestagenic

    . stanozolol https://www.ncbi.nlm.nih.gov/pubmed/8079819 ...indicating that stanozolol binds to the progesterone receptor... ...These results indicate that the inhibition of DNA synthesis by stanozolol is elicited through the progesterone receptor... https://www.sciencedirect.com/science/article/pii/S0034528812003797 ... hindering progesterone activity... .
  12. dr. frankenstein

    Protein Powder Reviews

    well, to me, a superb anorexic, eat normal, around 1 gram of protein x kg is a fantastic option (from normal food). EAAs, not gas ! is a cool slogan .
  13. dr. frankenstein

    Protein Powder Reviews

    maybe not just 3 grams 3 grams EAAs vs WP 20 grams https://www.physiology.org/doi/full/10.1152/ajpendo.00481.2014 ...We determined the effects of two feeding regimes in older women (66 ± 2.5 yr; n = 8/group): bolus whey protein (WP-20 g) or novel low-dose leucine-enriched essential amino acids (EAA) [LEAA; 3 g (40% leucine)]... ...In response to FED, both WP and LEAA equally stimulated MPS 0–2 h (P < 0.05), abating thereafter (0–4 h, P > 0.05). In contrast, after FED-EX, MPS increased at 0–2 h and remained elevated at 0–4 h (P < 0.05) with both WP and LEAA. No anabolic signals quantifiably increased after FED, but p70 S6K1 Thr389 increased after FED-EX (2 h, P < 0.05). APS increased similarly after WP and LEAA... .
  14. dr. frankenstein

    The first (of many?) Non-nutritive sweetener study you can't ignore?

    . Interesting, without alter Insulin... Carbohydrate Mouth Rinse Improves Cycling Time-Trial Performance without Altering Plasma Insulin Concentration. J Sports Sci Med. 2018 Mar 1;17(1):145-152. Murray KO, Paris HL, Fly AD, Chapman RF, Mickleborough TD. .
  15. dr. frankenstein

    The first (of many?) Non-nutritive sweetener study you can't ignore?

    https://academic.oup.com/ajcn/article/95/1/78/4576693 ...In healthy humans, SGLT1 substrates stimulate GLP-1 and GIP and slow gastric emptying, regardless of whether they are metabolized, whereas the artificial sweetener sucralose does not... https://sci-hub.tw/10.1093/ajcn/nqy152 hypothesizing on the hypothesized ...There are several potential mechanisms to explain the decreased insulin sensitivity associated with sucralose consumption, such as the interaction with sweet taste receptors T1R2 and T1R3 in pancreatic β cells and enteroendocrine cells promoting insulin and GLP-1 release, respectively (5–8). In addition, the increased expression of SGLT-1 and GLUT-2 transporters stimulates active and passive glucose transport... Interesting Intestinal Metabolism and Bioaccumulation of Sucralose In Adipose Tissue In The Rat. https://www.ncbi.nlm.nih.gov/pubmed/30130461/ but obvious ...daily for 40 days at an average dosage of 80.4 mg/kg/day.... . .
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