During the 2000s, the Melanotan II peptide and the metabolite derived from it, the erectile dysfunction-focused Bremelanotide (also known as PT-141), were patented and then licensed to biotechnology companies hoping to develop them into profitable prescription drugs. However, these companies also offer the peptides for direct sale to researchers. These transactions occupy a legal gray area, since the peptides are banned for human use outside clinical trials. While they can be purchased from various websites specializing in research chemicals, the purchaser usually has to affirm prior to final sale that the peptide "will not be used for human consumption" and is being acquired for "research purposes only."
Oxytocin is a peptide of nine amino acids (a nonapeptide). The sequence is cysteine - tyrosine - isoleucine - glutamine - asparagine - cysteine - proline - leucine - glycine (CYIQNCPLG). The cysteine residues form a sulfur bridge. Oxytocin has a molecular mass of 1007 daltons. One international unit (IU) of oxytocin is the equivalent of about 2 micrograms of pure peptide.
Thymosin β4 was initially perceived as a thymic hormone. However this changed when it was discovered that it forms a 1:1 complex with G (globular) actin, and is present at high concentration in a wide range of mammalian cell types. When appropriate, G-actin monomers polymerize to form F (filamentous) actin, which, together with other proteins that bind to actin, comprise cellular microfilaments. Formation by G-actin of the complex with β-thymosin (= "sequestration") opposes this.
Stimulation of uterine smooth muscle contraction at birth: At the end of gestation, the uterus must contract vigorously and for a prolonged period of time in order to deliver the fetus. During the later stages of gestation, there is an increase in abundance of oxytocin receptors on uterine smooth muscle cells, which is associated with increased "irritability" of the uterus (and sometimes the mother as well). Oxytocin is released during labor when the fetus stimulates the cervix and vagina, and it enhances contraction of uterine smooth muscle to facilitate parturition or birth.
Don’t take it by itself, you want to take it with a meal. The half life seems to vary; some people just need to take a single dose daily whereas some break it up into several doses. The dosage range is pretty wide, from 50 to 900 milligrams. Many report the antidepressant effect desired from lower doses, so start low with this one. Do not use a liquid form of 5-HTP.
Hi Ben, I have been using TB-500 for minor injury repair assistance for more than 2 years. I have found it to be extremely effective for minor strains to calves, hamstring, shoulder etc. Luckily I have not had to try it for any major injuries. When I first used it I was blown away by how effectively it worked – even to the point that I began to doubt the seriousness of the original injury. When injured I dose at 5mg per week for four weeks then take at least four weeks break. The only side affect I have noticed is a little light headed feeling which passes pretty quickly. I am in my late 40’s and I train hard. TB-500 allows me to train through minor injuries which is great. Love your work
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).
Oxytocin is known to be metabolized by the oxytocinase, leucyl/cystinyl aminopeptidase. Other oxytocinases are also known to exist. Amastatin, bestatin (ubenimex), leupeptin, and puromycin have been found to inhibit the enzymatic degradation of oxytocin, though they also inhibit the degradation of various other peptides, such as vasopressin, met-enkephalin, and dynorphin A.
Cells that line blood vessels (endothelial cells), taken from human umbilical chord veins, were grown in culture and the layer of cells subjected to a scratch wound. Cultures were then treated with Tb4 or kept in growth medium without Tb4. When examined four hours later, Tb4 treatment attracted cells to migrate into the wound and accelerated their movement, showing it is a chemoattractant. Cell migration was four to six times faster in the presence of Tb4 compared to the migration of untreated cells. Tb4 also hastened wound closure and increased the production of enzymes, called metalloproteases, that could pave the way for angiogenesis by breaking down barrier membranes and facilitating the invasion of new cells to the needy area, to form new vessels. Other experiments showed Tb4 acts in vivo. When endothelial cells were implanted under the skin in a gel supplemented with Tb4, the cells formed vessel-like structures containing red blood cells, indicating the ability to stimulate angiogenesis in the animals.
These results were in agreement with previous studies that showed Wnt5a expression can be induced in activated macrophages, endothelial cells, and bone marrow mesenchymal stem cells (BMSCs) after inflammatory stimulation [58, 59]. In addition, we found that the effects of Tβ4 peptide on H2O2-mediated induction of pro-inflammatory cytokines (NO, PGE2, TNF-α, IL-1β, IL-6, IL-8, and IL-17), the expression of inflammatory mediators (iNOS and COX-2), osteoclastogenic cytokines (cathepsin-K, calcitonin receptor or Calcr, NFATc1, and RANK), and osteoclastic differentiation, were reversed by exogenous treatment with Wnt5a siRNA but enhanced by rh-Wnt5a, suggesting that the anti-inflammatory and anti-osteoclastogenetic effects of Tβ4 activation were involved the Wnt5a-dependent signaling pathway. Similar to our results, Wnt5a knock-down markedly reduced cytokine/chemokine production induced by TNF in HDPCs .
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 and dynorphin, for example, that act locally. The magnocellular neurosecretory cells that make oxytocin are adjacent to magnocellular neurosecretory cells that make vasopressin. These are large neuroendocrine neurons which are excitable and can generate action potentials.
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.
Indeed, the findings that progenitor cells of some form exist both in the regenerative zebrafish heart, and in the hearts of less-regenerative mammals supports this idea. Zebrafish have ostensibly found some method to optimize the activity of progenitor cells, perhaps either by maintaining more cells, or by harboring a more cultivating environment for regeneration. Also, both mammalian and nonmammalian hearts contain an epicardial cell layer, yet zebrafish have found some way to activate the epicardium after injury, a process linked with essential neovascularization of regenerating muscle (Lepilina et al., 2006. This result points to the adult mammalian epicardium as a potential cellular source to assist myocardial regeneration or survival. Indeed, mammalian myocardial infarcts typically show poor or insufficient neovascularization, a response that many are trying to improve experimentally. Recent findings have indicated that the G-actin sequestering protein, Thymosin-ß4, may influence the mammalian epicardium. Treatment of adult cardiac explants with Thymosin-ß4 induced the migration of fibroblasts, endothelial and smooth muscle cells as assessed by gene expression and cellular morphology (Smart et al., 2007). In addition, in vivo Thymosin-ß4 treatment could partially restore cardiac survival and function following coronary ligation (Bock-Marquette et al., 2004). Notably, Thymosin-ß4 expression is induced in the injured zebrafish heart, suggesting that fish naturally release this epicardial stimulant on injury (Lien et al., 2006).
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.
“Ultimately you’re body is going to down-regulate the enzymes needed to convert the tyrosine/l-phenylalanine into dopamine and norepinephrine; this also counts for 5 -htp being converted into serotonin. As far as I’m aware when simply supplementing amino acids to improve neurotransmitter prevalence in the brain, tolerance will build very rapidly within a one week to two week period (from personal experience). Not saying it’s not viable to help out with mood when used sparingly, just saying there’s most likely better ways for continued treatment.”
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.
Plain sterile water is the most suitable diluent for TB-500. Alternatively it can be reconstituted with sterile saline (0.9% NaCl) or sterile bacteriostatic water (0.9% sodium chloride). Plain sterile water should be readily available to buy without prescription in any local pharmacy. Alternatively it can also be purchased online. It is even available on ebay.
Oxytocin is known as the hormone that promotes feelings of love, bonding and well-being. It's even being tested as an anti-anxiety drug. But new research shows oxytocin also can cause emotional pain. Oxytocin appears to be the reason stressful social situations, perhaps being bullied at school or tormented by a boss, reverberate long past the event and can trigger fear and anxiety in the future. That's because the hormone actually strengthens social memory in the brain.
Oxytocin's story starts back in the early 1900s, when biochemists discovered that a substance from the posterior pituitary gland could promote labour contractions and lactation. When scientists later discovered the hormone responsible, they named it oxytocin after the Greek phrase meaning 'rapid birth'. Oxytocin is produced mainly by the brain's hypothalamus; in the 1970s, studies revealed that oxytocin-producing neurons send signals throughout the brain, suggesting that the hormone had a role in regulating behaviour.
Dr Sohère Roked is a GP in the UK with a specialist interest in integrative medicine. She prescribes 5-HTP to patients with anxiety and depression, alongside vitamins and other natural supplements, and sees no problem with it being used for mild conditions. "With the patients I see, generally I've seen good results with it. Antidepressants do work for some people, so I'm not against them completely, but others don't want to go down that path straight away. This gives them another option."
Thymosin Beta 4 is a potent peptide that comes from a family of 16 related molecules that are localized in circulating cells and tissues within the body. These molecules also have a high conservation of sequence. TB 500 conjoins with actin and prevents actin polymerization. It is noted as being the actin-sequestering molecule within eukaryotic cells. It also boosts extracellular matrix-degrading enzyme production.
Hey I have used Tb 500 alot and can tell you injecting it in your fat around your stomach or in your large muscles near the injury is fine. I would never inject it into a wounded area because of possiblity of making the area worse by infection or trama from the needle. Dosage is tough I would say for a 200 pound person you need at least 5mg twice a week. Mixing it with GH releasing peptides seems to make it stronger as well. It’s definitely worth the month just finding legit stuff can be tricky.
Romantic attachment: In some studies, high levels of plasma oxytocin have been correlated with romantic attachment. For example, if a couple is separated for a long period of time, anxiety can increase due to the lack of physical affection. Oxytocin may aid romantically attached couples by decreasing their feelings of anxiety when they are separated.
While all of the effects described above certainly occur in response to oxytocin, doubt has recently been cast on its necessity in parturition and maternal behavior. Mice that are unable to secrete oxytocin due to targeted disruptions of the oxytocin gene will mate, deliver their pups without apparent difficulty and display normal maternal behavior. However, they do show deficits in milk ejection and have subtle derangements in social behavior. It may be best to view oxytocin as a major facilitator of parturition and maternal behavior rather than a necessary component of these processes.
Osteoclast differentiation was assessed by tartrate-resistant acid phosphatase (TRAP) staining and activity. After 5 days of culture, cells were stained for TRAP kit using a leukocyte acid phosphatase kit (Sigma Aldrich, St Louis, MO, USA). Cells with three or more nuclei were counted as multinucleated mature osteoclasts. To measure TRAP activity, cells were fixed with 10% formalin for 10 min and 95% ethanol for 1 min, and then 100 μl of citrate buffer (50 mM, pH 4.6) containing 10 mM sodium tartrate and 5 mM p-nitrophenylphosphate (Sigma-Aldrich) was added to the wells containing fixed cells in the 48-well plates. After incubation for 1 h, enzyme reaction mixtures in the wells were transferred to new plates containing an equal volume of 0.1 N NaOH. Absorbance was measured at 410 nm using a microplate reader.
Thymosin beta 4 accelerated skin wound healing in a rat model of a full thickness wound where the epithelial layer was destroyed. When Tb4 was applied topically to the wound or injected into the animal, epithelial layer restoration in the wound was increased 42% by day four and 61% by day seven, after treatment, compared to untreated. Furthermore, Tb4 stimulated collagen deposition in the wound and angiogenesis. Tb4 accelerated keratinocyte migration, resulting in the wound contracting by more than 11%, compared to untreated wounds, to close the skin gap in the wound. An analysis of skin sections (histological observations) showed that the Tb4 treated wounds healed faster than the untreated. Proof of accelerated cell migration was also seen in vitro, where Tb4 increased keratinocyte migration two to three fold, within four to five hours after treatment, compared to untreated keratinocytes.
Oxytocin was also correlated with the longevity of a relationship. Couples with the highest levels were the ones still together six months later. They were also more attuned to each other than the low-oxytocin couples when Feldman asked them to talk about a shared positive experience. The high-oxytocin couples finished each other’s sentences, laughed together and touched each other more often. Feldman says it’s still not clear whether oxytocin was responsible for the stability of the couple’s bond six months later or if couples who weren’t as connected failed to trigger the oxytocin system.
In this study, Tβ4 mRNA down-regulation was detected in in vitro in PDLCs stimulated with the ROS. This down-regulation of Tβ4 was also observed in GCF of periodontitis patient  and endotoxin-induced septic shock of rats . ROS were generated predominantly by polymorphonuclear leukocytes (PMN) during an inflammatory response and involved in tissue destruction associated with periodontal diseases . Thus, we chose to use ROS-stimulated PDLCs in this study since ROS, such as superoxide and H2O2, have been proposed as key players in bone resorption  and implicated in the pathogenesis of rheumatoid arthritis and periodontitis .
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.
How would that work? Feldman thinks that these types of behaviors are intimately linked with oxytocin in a positive feedback loop. “Oxytocin can elicit loving behaviors, but giving and receiving these behaviors also promotes the release of oxytocin and leads to more of these behaviors,” she says. She thinks that talk therapy alone can boost the oxytocin system, but admits that in some cases it might help to jump-start the feedback loop by administering oxytocin. If Guastella’s results support his hypothesis, talk and hormone therapy together might be the best recipe for breaking down dysfunctional communication between partners, especially in cases where the behaviors have been learned in childhood.
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At first, the mice showed an irregular smattering of neural impulses when they heard the baby's cries. Then, as the oxytocin kicked in, the signal evolved into a more orderly pattern typical of a maternal brain. The study showed in unusual detail how the hormone changed the behaviour of neurons1. “Oxytocin is helping to transform the brain, to make it respond to those pup calls,” Froemke says.
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;94:127-131. View abstract.
Children: 5-HTP is POSSIBLY SAFE when taken by mouth appropriately. Doses of up to 5 mg/kg daily have been used safely for up to 3 years in infants and children up to 12 years-old. As with adults, there is also concern about the potential for eosinophilia-myalgia syndrome (EMS) in children, a serious condition involving extreme muscle tenderness (myalgia) and blood abnormalities (eosinophilia).