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Myocardial infarction and heart failure are severe causes for death in humans. Extracellular nucleotides (ATP and ADP) released at the site of myocardial damage induce thrombosis, apoptosis and necrosis. ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1, CD39) rapidly hydrolyzes ATP and ADP to AMP. An in vivo myocardial ischemia/reperfusion injury test in transgenic mice expressing human CD39 resulted in a decrease of the infarct size. The same transgene including the human CD39 cDNA driven by the murine MHC class I gene H-2Kb promoter was used for the generation of transgenic pigs via SCNT. Expression of human CD39 was detected on circulating blood cells and in myocardial tissue of the transgenic animals. After in vivo induction of myocardial ischemia/reperfusion injury, a reduction of the myocardial injury analogous to the results in the transgenic mice was found (Wheeler et al., 2012).
Thymosin beta 4 (Tβ4) is a highly conserved, naturally occurring, water-soluble regenerative peptide that is found in all tissues and in all cell types, except red blood cells (Goldstein, Hannappel, Sosne, & Kleinman, 2012; Goldstein & Kleinman, 2015). It is also found in the blood and in other body fluids, including tears, saliva, cerebrospinal fluid, and wound fluids (Badamchian et al., 2007; Huang, Wang, Barnes, & Elmets, 2006; Mohring, Kellmann, Jurgens, & Schrader, 2005). Both platelets and leukocytes release Tβ4 into the wound fluid such that the final concentration is 13 μg/mL (Fromm, Gunne, Bergman, et al., 1996; Hannappel & van Kampen, 1987).
Traumatic brain injury (TBI) remains a leading cause of mortality and morbidity worldwide. No effective pharmacological treatments are available for TBI because all Phase II/III TBI clinical trials have failed. This highlights a compelling need to develop effective treatments for TBI. Endogenous neurorestoration occurs in the brain after TBI, including angiogenesis, neurogenesis, synaptogenesis, oligodendrogenesis and axonal remodeling, which may be associated with spontaneous functional recovery after TBI. However, the endogenous neurorestoration following TBI is limited. Treatments amplifying these neurorestorative processes may promote functional recovery after TBI. Thymosin beta4 (Tβ4) is the major G-actin-sequestering molecule in eukaryotic cells. In addition, Tβ4 has other properties including anti-apoptosis and anti-inflammation, promotion of angiogenesis, wound healing, stem/progenitor cell differentiation, and cell migration and survival, which provide the scientific foundation for the corneal, dermal, and cardiac wound repair multicenter clinical trials. Here, we describe Tβ4 as a neuroprotective and neurorestorative candidate for treatment of TBI.
Melanotan II is a synthetic analogue of the α-melanocyte stimulating hormone (α-MSH). α-MSH is a melanocortin I receptor agonist which has a role in human pigmentation by stimulating production of eumelanin. As melanotan II is a non-specific melanocortin receptor agonist, it has been reported to cause toxicity effects involving the many physiological systems affected by the receptors.
Actual injection can be done Subq or IM that is - subcutaneous or intramuscular. Injection site does not matter, there is no one site better than others so use one which is more comfortabe to reach, after injection product is absorbed into bloodstream and spread through the body evenly. Subq injection takes place by pinching the skin loose from the muscle and raising it so the needle can be inserted in the fat layer of skin.
My wife has suffered from debilitating leg cramps for years, usually nocturnal. We have spent much money and time trying to find a cure, including every type of magnesium supplement we could find. Nothing has worked. We’ve also tried MSM and DMSO. Sometimes the cramps are in her calves, sometimes her thighs, sometimes her back and even her toes. Sometimes several muscles cramp at once. She has a high tolerance for pain, but these cramps leave her sobbing. I have purchased TB-500 and received it today. Does your research offer any hope that this could help eliminate her muscle spasms?
Moreover, Tβ4 concentration revealed wide variability, and it decreased in the gingival crevicular fluid (GCF) as periodontal disease progressed . In contrast, Tβ4 mRNA expression was 3.76 fold higher in periodontitis-affected gingival tissue, compared with healthy individuals’ tissue obtained from public microarray data (GEO assession: GSE 23586) . However, the Tβ4 mRNA level did not change in the periodontal-diseased gingival tissue (arbitrary units; 6.249) when compared with healthy tissue (arbitrary units; 6.242) (GEO assession: GSE 10334) . Although Tβ4 exerts anti-inflammatory effects in vivo and in vitro, the precise role of Tβ4 in the inflammatory response remains unclear.
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It has been reported that deficiencies in the amino acid tryptophan (precursor to 5-HTP) are correlated with depression, as evidence by serum tryptophan in depressed persons. Decreased levels of tryptophan in the body can come from various means but are most likely caused by a diet lacking in the amino acid as substrate, or by upregulation of enzymes (most notably indoleamine 2,3-dioxygenase(IDO) and tryptophan 2,3-dioxygenase(TDO)) that degrade tryptophan or direct it to paths that are not serotonin synthesis causing a relative deficiency. These enzymes can be upregulated in states of chronic inflammation and injection of some pro-inflammatory cytokines has been implicated in depression and increasing the kyurenine:tryptophan ratio, which is indicative of IDO activity being increased. The activity of tryptophan hydroxylase can also be further downregulated in cases of Magnesium or vitamin B6 deficiency, stress, or excessive tryptophan levels.
Dietary supplements containing 5-HTP are claimed to help promote feelings of happiness and general well-being as well as a wide range of other positives such as appetite control, reduced anxiety, and improved mood, sleep and feelings of relaxation. However, there is no conclusive evidence showing that it is effective, and there is no clear "therapeutic" dose of 5-HTP.
For this study, one of us, Ben Trumble, followed Tsimane men as they went hunting for food. Typically, Tsimane men set out alone or with a partner in the early morning and search in the forest for prey such as wild pigs, deer, monkeys, or the rare tapir. Following long looping trails they might be gone for eight or nine hours, traveling about six miles (ten kilometers). Ben collected saliva samples throughout the hunt in order to measure changes in men’s hormone levels.
In a study measuring oxytocin serum levels in women before and after sexual stimulation, the author suggests it serves an important role in sexual arousal. This study found genital tract stimulation resulted in increased oxytocin immediately after orgasm. Another study reported increases of oxytocin during sexual arousal could be in response to nipple/areola, genital, and/or genital tract stimulation as confirmed in other mammals. Murphy et al. (1987), studying men, found oxytocin levels were raised throughout sexual arousal with no acute increase at orgasm. A more recent study of men found an increase in plasma oxytocin immediately after orgasm, but only in a portion of their sample that did not reach statistical significance. The authors noted these changes "may simply reflect contractile properties on reproductive tissue".
Affecting generosity by increasing empathy during perspective taking. In a neuroeconomics experiment, intranasal oxytocin increased generosity in the Ultimatum Game by 80% but has no effect in the Dictator Game that measures altruism. Perspective-taking is not required in the Dictator Game, but the researchers in this experimental explicitly induced perspective-taking in the Ultimatum Game by not identifying to participants which role they would be in.
Horvath, G. A., Stockler-Ipsiroglu, S. G., Salvarinova-Zivkovic, R., Lillquist, Y. P., Connolly, M., Hyland, K., Blau, N., Rupar, T., and Waters, P. J. Autosomal recessive GTP cyclohydrolase I deficiency without hyperphenylalaninemia: evidence of a phenotypic continuum between dominant and recessive forms. Mol.Genet.Metab 2008;94(1):127-131. View abstract.
Some work has pointed to a potential dark side to oxytocin. Carter's group found that a single low dose of the hormone given to baby prairie voles improved their pair bonding as adults, but that higher doses interfered with that behaviour — possibly because oxytocin started to activate other receptors16. And human studies have suggested that in certain contexts, a puff of oxytocin can cause people to be more aggressive in defending themselves against outsiders or competitors17. In patients with a psychiatric condition known as borderline personality disorder, a single dose of oxytocin has been found to hinder trust and cooperation18.
If you’re looking for hard proof that taking 5-HTP to lose weight works, we’ve got it: In a University of Rome study, obese women who took 5-HTP began eating between 1,000 to 2,000 fewer calories per day. And even as their caloric intake plummeted to a level that would leave many dieters irritable, serotonin was soothing these ladies — and not one reported hunger or diet crankiness. Further boosting spirits: The supplements quadrupled their weight loss, compared to folks given a placebo pill. “They ate a lot less than they normally would because it was easy for them,” Dr. Bhatia notes. Hearing about such an easy way to lose weight might be enough to inspire you to try the supplement for yourself. So, we went ahead and rounded up everything you need to know to get started.
Mouse bone marrow macrophage (BMMs) of 5-week-old female ICR mice (Charles River Laboratories, Seoul, South Korea) were used as previously described . Animals were maintained in accordance with the National Institute of Toxicological Research of the Korea Food and Drug Administration guideline for the humane care and use of laboratory animals Institutional Animal Care and Use Committee (IACUC) approval was obtained from Kyung Hee University (Seoul, Korea). Briefly, bone marrow of tibiae and femurs of mice were flushed with α-MEM. After removing erythrocytes with hypotonic buffer, cells were cultured in α-MEM containing 10% FBS for 24 h and adherent cells were discarded. Non-adherent bone marrow cells were transferred onto 100-mm non-coated petri dishes at 5×106 cells per dish and cultured in the presence of M-CSF (30 ng/ml) for 3 days. Condition medium (CM) was obtained from HPDLCs treated with 200 μM H2O2 or Tβ4 (0.5, 1 and 5 μg/mL) for 2 days. To evaluate the osteoclastogenic activity of CM from HPDLCs, we added the CM mixture (60% CM plus 40% fresh α-MEM without M-CSF or RANKL) or rh-Tβ4 to pre-osteoclast-stage cells and further cultured the cells for up to 5 days to achieve mature osteoclast differentiation BMMs (1.5 × 105 cells/well) and PDLCs (1.5 × 104 cells/well) were co-cultured for 7 days in the presence of M-CSF (30 ng/ml), RANKL (100 ng/mL), H2O2 (200 μM) or Tβ4 (0.5, 1 and 5 μg/mL) in α-MEM, supplemented with10% in 48-well plates under 5% CO2 atmosphere.
Jump up ^ Carlier MF, Hertzog M, Didry D, Renault L, Cantrelle FX, van Heijenoort C, Knossow M, Guittet E (September 2007). "Structure, function, and evolution of the beta-thymosin/WH2 (WASP-Homology2) actin-binding module". Annals of the New York Academy of Sciences. 1112: 67–75. Bibcode:2007NYASA1112...67C. doi:10.1196/annals.1415.037. PMID 17947587.
James Bates* who recently started taking it for panic attacks, said, "A friend who had anxiety recommended 5-HTP to me. I used to take beta-blockers and Valium but the doctors have got funny about giving them to me. I needed an alternative and didn't fancy getting back on Prozac. I've only been taking the supplements for a month but so far, it's helped a lot. I've only had two panic attacks, whereas usually I'd have four or five."
TB-500 is a synthetic version of the naturally occurring peptide present in virtually all human and animal cells, Thymosin Beta-4. This potent peptide is a member of a ubiquitous family of 16 related molecules with a high conservation of sequence and localization in most tissues and circulating cells in the body. TB-500 not only binds to actin, but also blocks actin polymerization and is the actin-sequestering molecule in eukaryotic cells.
Side effects: Nausea, fatigue, facial flushing, reaction at injection site, appetite suppression. The potential for side effects to occur increases with an increased dose of Melonotan, and decreases both with a lesser dose and with regular administration. The exception to this is physical signs of sexual arousal, namely male erection when using MT2. So it is important that users of MT II are aware of this before administering.
Cognitive impairment has repeatedly been described in bipolar disorders… Serotonin (5-hydroxytryptophan; 5-HT) is possibly involved in these cognitive processes, more particularly in executive functions, learning, memory, and attention. The aim of this study was to investigate serotonergic vulnerability and its relation to cognitive functioning in healthy first-degree relatives of [bipolar disorders] patients…
The scientists discovered that oxytocin strengthens negative social memory and future anxiety by triggering an important signaling molecule -- ERK (extracellular signal regulated kinases) -- that becomes activated for six hours after a negative social experience. ERK causes enhanced fear, Radulovic believes, by stimulating the brain's fear pathways, many of which pass through the lateral septum. The region is involved in emotional and stress responses.
Once the baby is born, oxytocin promotes lactation by moving the milk into the breast. When the baby sucks at the mother's breast, oxytocin secretion causes the milk to release so the baby can feed. At the same time, oxytocin is released into the brain to stimulate further oxytocin production. Once the baby stops feeding, the production of the hormone stops until the next feeding.
The hormone does not act alone. In 2013, neuroscientist Robert Malenka at Stanford University in California and his colleagues showed that oxytocin works together with the neurotransmitter serotonin to reduce the excitability of neurons in the nucleus accumbens9, a brain region involved in reward. This process seems to support the preference of mice to return to environments where they had rewarding social interactions with other animals. “Oxytocin is part of a system,” Carter says, “and it's not the only molecule that matters, but it's one that in some way is regulatory over a large number of other systems.”
20 patients (nine from the 5-HTP group and 11 from the Placebo group) completed the study. Brain tryptophan availability in diabetic patients was significantly reduced when compared to a group of healthy controls. Patients receiving 5-HTP significantly decreased their daily energy intake, by reducing carbohydrate and fat intake, and reduced their body weight.”
Noteworthy: Many online sources sell an ineffective product. Also, peptides are fragile by nature and are not effective when they are taken orally (pills, shakes, etc) because they will be broken down by the digestive process. Instead, peptides are mixed with bacteriostatic water and then injected under the skin with an insulin needle. Peptide injections in this manner are nearly painless and have clinically proven effectiveness.
Oxytocin and vasopressin are the only known hormones released by the human posterior pituitary gland to act at a distance. However, oxytocin neurons make other peptides, including corticotropin-releasing hormone (CRH) and dynorphin, for example, that act locally. The magnocellular neurons that make oxytocin are adjacent to magnocellular neurons that make vasopressin, and are similar in many respects.
An estimated 1.4 million people sustain traumatic brain injury (TBI) each year in the United States, and more than 5 million people are coping with disabilities from TBI at an annual cost of more than $56 billion.1 There are no commercially-available pharmacological treatment options available for TBI because all clinical trial strategies have failed.2,3 The disappointing clinical trial results may be due to variability in treatment approaches and heterogeneity of the population of TBI patients.4-9 Another important aspect is that most clinical trial strategies have used drugs that target a single pathophysiological mechanism, although many mechanisms are involved in secondary injury after TBI.4 Neuroprotection approaches have historically been dominated by targeting neuron-based injury mechanisms as the primary or even exclusive focus of the neuroprotective strategy.3 In the vast majority of preclinical studies, the treatment compounds are administered early and, frequently, even before TBI.10,11 Clinically, the administration of a compound early may be problematic because of the difficulty in obtaining informed consent.12
We think that the most important region is the nucleus accumbens, which is kind of up here. The nucleus accumbens is where we can measure a release of the neurotransmitter dopamine when humans or animals take drugs or are exposed to other rewarding stimuli, such as sex. Or gambling, for example, or monetary reward activates the nucleus accumbens as well.
The molecule of this peptide is very big, so it isn’t able to completely fit within a receptor. Each area of the molecule has different functions. For instance, TB 500 is responsible for promoting majority of the useful effects, such as the healing, muscle cells, new blood and repair. In some scenarios, TB 500 could be used rather than the whole Thymosin Beta 4 protein. TB 500’s main ability is to regulate Actin, which is a cell-building protein. There are thousands of proteins found inside of cells, but actin makes up to 10 percent of the total amount of proteins, giving it a major role in the cell’s genetic makeup.
With the TB-500 it seems that pain was reduced even more in my shoulder and it appears that I recovered much faster from my workouts. I took the TB-500 on rest days. I have two more 1mg doses of TB-500 and I am going to site inject intramuscularly to the shoulder to see what happens. Then I will stop taking both for a month to see how things work out. Hopefully I won’t need them again.
In addition, in the Phase 1 clinical trial in healthy volunteers using a randomised, double-blind, placebo-controlled single- and multiple-dose Phase 1 clinical trial, the safety and pharmacokinetics of the intravenous administration of TB-4 was evaluated. From this, intravenous administration of TB-4 appears to be safe and well-tolerated by all subjects with no dose limiting toxicity or serious adverse events reported.
Virtually all vertebrates have an oxytocin-like nonapeptide hormone that supports reproductive functions and a vasopressin-like nonapeptide hormone involved in water regulation. The two genes are always located close to each other (less than 15,000 bases apart) on the same chromosome and are transcribed in opposite directions. It is thought that the two genes resulted from a gene duplication event; the ancestral gene is estimated to be about 500 million years old and is found in cyclostomes (modern members of the Agnatha).
A study using an oral cavity spray of 5-HTP (via the plant source of Griffonia Simplicifolia) has noted that 7.68mg of 5-HTP via 30.72mg of Griffonia Simplicifolia extract taken five times daily (total daily dose of around 40mg) has confirmed an increase in urinary 5-HIAA (from 3.71+/-1.27mg/24 hours to 8.80+/-4.02mg/24 hours; a 137% increase) relative to baseline, confirming that 5-HTP can be absorbed sublingually. Similar results have been noted elsewhere with this spray, although it should be noted that it is confounded with other herbs (detailed in the appetite subsection).
Injection is the most effective way to administrate the peptide and results are seen the fastest and best. The nasal spray method is effective up to 30 – 40% because the nasal passages have poor absorption rate, you have to apply the nasal spray at least two to three times more than the injection. The injectable product of the Melanotan is very superior as compared to the nasal version. The nasal versions generally take four to five weeks for displaying the results appose to 10 days with the injection.
Reconstituting tanning peptide is a part of the process required for use of the product and will require full attention to get proper results. 1 or 2ml sterile water is usually used, diluting with more water will improve dosing accuracy. Lovemelanotan peptide calculator is ideal tool for anyone just starting out and not sure how to reconstitute or dose the product properly.
Much of human behavior is influenced by hormones. There’s cortisol, involved in our stress response and energy balance. Testosterone, a male sex hormone, tends to make men more competitive. Oxytocin has various social and physiological functions in the brain and the body, but is sometimes referred to as the “love hormone” due to its role in social bonding. These are all simplifications, but hormones do underlie many aspects of what we do and what we feel.
In mammals, many mysteries remain. Oxytocin is difficult to measure reliably in the brain, making it hard to know exactly where, when and how much is normally released; nor do scientists understand precisely how it works to alter behaviour. “What we need to start thinking about is the more fundamental role that oxytocin plays in the brain,” Young says. The determination to find out has been strengthened by a growing move in neuroscience to characterize circuits that are important in brain operations. “That's the level that's critical for understanding how the brain is regulating behaviour,” says Thomas Insel, director of the US National Institute of Mental Health in Bethesda, Maryland, who has studied oxytocin in voles.
Researchers often investigate the effects of hormones on behavior in laboratory experiments with student subjects. Some studies show that when you give people oxytocin they become more generous and trusting. In others that administer testosterone to men, the opposite happens. The strength of such studies is that they can demonstrate cause and effect – the behavior change only occurs in subjects receiving hormones, not in those who get a placebo. But this research has weaknesses as well: it often focuses on single hormones, ignoring their potential interactions, and behavior is measured with highly artificial tasks.
It turns out the love hormone oxytocin is two-faced. Oxytocin has long been known as the warm, fuzzy hormone that promotes feelings of love, social bonding and well-being. It's even being tested as an anti-anxiety drug. But new Northwestern Medicine® research shows oxytocin also can cause emotional pain, an entirely new, darker identity for the hormone.
^ Jump up to: a b Takayanagi Y, Yoshida M, Bielsky IF, Ross HE, Kawamata M, Onaka T, Yanagisawa T, Kimura T, Matzuk MM, Young LJ, Nishimori K (November 2005). "Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice". Proceedings of the National Academy of Sciences of the United States of America. 102 (44): 16096–101. Bibcode:2005PNAS..10216096T. doi:10.1073/pnas.0505312102. PMC 1276060. PMID 16249339.
5-HTP appears to reduce food intake secondary to increasing satiety, although most studies are currently conducted in women (in regards to 5-HTP being related to serotonin, this may be relevant; see our creatine page and the Depression section for more information). At least one study that was mixed gender supports the notion it benefits both genders, however
This is exactly the type of question myself, my team of coaches and the community in my Inner Circle can help to answer for you. The Inner Circle is a collective of people who are pursuing the same goals you are – trying to live a healthy, happy, adventurous, fulfilling and limitless life in a modern world. In the Inner Circle, we all help each other with questions, ideas, motivation, suggestions and much more!
Sexual activity has been found to stimulate the release of oxytocin, and it appears to have a role in erection and orgasm. The reason for this is not fully understood, but, in women, it may be that the increased uterine motility may help sperm to reach their destination. Some have proposed a correlation between the concentration of oxytocin and the intensity of orgasm.
Research in the early 1960s showed that in rats, administration of α-MSH caused sexual arousal, and work on this continued in many labs up through the 1980s, when scientists at University of Arizona began attempting to develop α-MSH and analogs as potential sunless tanning agents, and synthesized and tested several analogs, including melanotan-I and melanotan II.
Jump up ^ PDB: 1HJ0; Stoll R, Voelter W, Holak TA (May 1997). "Conformation of thymosin beta 9 in water/fluoroalcohol solution determined by NMR spectroscopy". Biopolymers. 41 (6): 623–34. doi:10.1002/(SICI)1097-0282(199705)41:6<623::AID-BIP3>3.0.CO;2-S. PMID 9108730. The thymosin is β9, bovine orthologue of human β10. Stabilised by organic solvent, the structure was determined by NMR. (Free β-thymosins lack a stable fold in solution)
Growing up, Joe was plagued with a myriad of health issues such as gut problems, autoimmune issues, chronic fatigue, brain fog, insomnia, and general inflammation. Both conventional and alternative doctors weren’t able to help him, so he decided to fix himself. With lots of health questions and few satisfying answers, Joe decided to read every research paper he could get his hands on and conduct thousands of experiments on his own body in order to fix his health issues. Joe started SelfHacked in late 2013 when he successfully fixed all of his issues, and now it gets millions of readers a month looking to educate themselves about how they can improve their health. Joe is now a thriving author, speaker, and serial entrepreneur, founding SelfDecode & LabTestAnalyzer.