The mRNA and protein expressions were determined by PCR analysis (A) and Western blot analysis (B), respectively. The bar graph shows the fold increase in protein or mRNA expression compared with control cells * Statistically significant differences compared with the control, p<0.05. The data presented were representative of three independent experiments.
In a landmark 1979 study3, Cort Pedersen and Arthur Prange at the University of North Carolina in Chapel Hill showed that giving oxytocin to virgin rats could trigger maternal behaviours: the animals would build nests, lick or crouch over unfamiliar pups and even return lost pups to the nest. Researchers went on to show that oxytocin signalling in the brains of prairie voles (Microtus ochrogaster) helps the animals to form lifelong pair bonds4 — a rarity among mammals. In 2012, researchers even found a version of oxytocin in the tiny roundworm Caenorhabditis elegans, where it helps the animals find and recognize mates5.
The uterine-contracting properties of the principle that would later be named oxytocin were discovered by British pharmacologist Sir Henry Hallett Dale in 1906, and its milk ejection property was described by Ott and Scott in 1910 and by Schafer and Mackenzie in 1911. In the 1920s, oxytocin and vasopressin were isolated from pituitary tissue and given their current names. The word oxytocin was coined from the term oxytocic, Greek ὀξύς, oxys, and τοκετός , toketos, meaning "quick birth".
A and B; Mouse BMMs were cultured with 200 μM H2O2 and indicated concentrations of Tβ4 peptide in the presence of M-CSF (30 ng/mL) and RANKL (100 ng/mL). C and D; PDLCs were co-cultured with mouse BMMs in the presence of M-CSF, RANKL, 200 μM H2O2, and indicated concentrations of Tβ4 peptide. To monitor osteoclast differentiation, both TRAP activity and the number of TRAP multinucleated cells were examined. * Statistically significant difference compared with control, p<0.05. The data presented were representative of three independent experiments.
According to recent research, this hormone “is now believed to be involved in a wide variety of physiological and pathological functions such as sexual activity, penile erection, ejaculation, pregnancy, uterine contraction, milk ejection, maternal behavior, social bonding, stress and probably many more, which makes oxytocin and its receptor potential candidates as targets for drug therapy. From an innocuous agent as an aid in labor and delivery, oxytocin has come a long way in being touted as the latest party drug.”4
Treatment of patients with hyperbaric oxygen has been shown to improve the healing of chronic lower extremity wounds of diabetic patients (Londahl et al., 2010). In a pilot study, this treatment has been shown to more than double the number of circulating vascular stem/progenitor cells in these patients by a mechanism that elevates platelet NOS activity and to stimulate recruitment of vascular progenitor cells to wounds made in their abdominal skin (Thom et al., 2011). This treatment might be combined with topical agents for even greater efficacy in healing chronic wounds.
Interestingly, there are numerous differences in the biology of teleosts and mammals, as well as specific differences in cardiomyocyte cellular structure and anatomy, all of which might contribute to regenerative variability. Unlike mammals, zebrafish can grow throughout most of adulthood, a phenomenon called “indeterminate growth” (Jordan, 1905). In fact, their growth can be affected markedly by changes in nutrition and population density (Goldsmith et al., 2006). It is thus possible that the capacity to replace cardiac tissue rapidly in teleosts has been retained in evolution as a function of the need for robust animal and cardiac growth. Indeed, a recent study has found that experimentally-induced adult cardiac growth in zebrafish is hyperplastic, and appears to rely on the same signals present or required during cardiac regeneration (Wills et al., 2008).
In humans, 5-HTP is the nutrient precursor to the neurotransmitter serotonin – widely known as the 'happy neurotransmitter' – meaning 5-HTP converts directly into serotonin in the brain. As well as being in our bodies, it's found naturally in the seeds of a woody shrub native to West Africa. By taking it as a supplement, in theory, you will end up with more serotonin in your brain. Serotonin deficiency is linked to depression, anxiety and a whole host of physical and mental ailments. Raising its levels seems to help brain cells send and receive chemical messages, which in turn boosts mood.
Jump up ^ Low TL, Hu SK, Goldstein AL (February 1981). "Complete amino acid sequence of bovine thymosin beta 4: a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations". Proceedings of the National Academy of Sciences of the United States of America. 78 (2): 1162–6. Bibcode:1981PNAS...78.1162L. doi:10.1073/pnas.78.2.1162. PMC 319967. PMID 6940133.
For all its positivity, however, oxytocin has a dark side. Or, more accurately, it plays a more complex role in human behavior than is commonly thought. As a facilitator of bonding among those who share similar characteristics, the hormone fosters distinctions between in-group and out-group members, and sets in motion favoritism toward in-group members and prejudice against those in out-groups. Ongoing research on the hormone is a potent reminder of the complexity of biological and psychological systems.
Melanotan 2 works by stimulating the release of the pigment melanin from the skin. Less UV exposure is necessary with Melanotan 2 compared to “normal tanning”, and the tan that occurs with tanning injections is deeper and longer lasting than an individual’s “normal tan”. Melanotan works best (has the most noticeable effects) on people with fair skin tones.
The first time Ditzen and her colleagues did this experiment they found that for both men and women oxytocin improved communication and lowered cortisol, a stress hormone. But in a recent study published in Social Cognitive and Affective Neuroscience, Ditzen and her colleagues measured salivary alpha-amylase (sAA)—an enzyme tied specifically to social stress—and found that men and women responded differently. Women who got oxytocin showed a decrease in sAA whereas men showed an increase and reported feeling more intense emotions. Counterintuitively, these men were also better at communication during conflict: they smiled more, had more eye-contact and were more open about their feelings. These behaviors are essential for peaceful conflict resolution.
Jump up ^ Wei D, Lee D, Cox CD, Karsten CA, Peñagarikano O, Geschwind DH, Gall CM, Piomelli D (November 2015). "Endocannabinoid signaling mediates oxytocin-driven social reward". Proceedings of the National Academy of Sciences of the United States of America. 112 (45): 14084–9. Bibcode:2015PNAS..11214084W. doi:10.1073/pnas.1509795112. PMC 4653148. PMID 26504214.
In 1989, a nationwide outbreak sickened over 1500 people and caused at least 30 deaths in the US. The outbreak was characterized by severe muscle pain and high white blood cell count. The culprit was later determined to be tryptophan supplements made by a specific manufacturer that were thought to be contaminated. Shortly thereafter, the FDA recalled and banned all forms of tryptophan supplements. In the meantime, an alternative supplement called 5-hydroxytryptophan (5-HTP), which is a chemical byproduct of tryptophan, was introduced as an alternative and has since become popular.
Although maternal bonding may not always be hardwired — after all, human females can adopt babies and take care of them — oxytocin released during pregnancy "does seem to have a role in motivation and feelings of connectedness to a baby," Young said. Studies also show that interacting with a baby causes the infant's own oxytocin levels to increase, he added.
The pamphlet, titled "Melanotan-2: Safe enhanced tanning" says although the drug is not approved by the Therapeutic Goods Administration (Australia's drug watchdog) and that studies into its effects are under way, it "is safe" and and its use "well documented". It says people can be referred to a "suitable doctor who is trained to prescribe MT2" so the pharmacy can dispense it to them.
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.
Melanotan II can be of unknown quality and subject to contamination and stability concerns with use of multi-dose vials. There is no experience with the product other than through unregulated channels. There are health risks from the substance itself and its route of administration – documented in medical literature, case reports as well as reports from NSW PIC.
The tb-500 has a systematic effect regardless of where it is injected. Some believe that thymosin beta-4 should be injected as close to the injury as possible however there is no evidence to show this would be superior. It can be injected subcutaneously (stomach fat) or intramuscularly (shoulders, thighs, buttocks). Injections should be given in different sites (rotated) each time. Depending on the spot, you can either feel nothing or you can feel slight pain - you will learn your favorite spots in time.
Thymosin is a hormone secreted from the thymus. Its primary function is to stimulate the production of T cells, which are an important part of the immune system. Thymosin also assists in the development of B cells to plasma cells to produce antibodies. The predominant form of thymosin, thymosin b4, is a member of a highly conserved family of actin monomer-sequestering proteins. b-thymosins are the primary regulators of unpolymerized actin, and are essential for maintaining the small cytoplasmic pool of free G-actin monomers required for rapid filament elongation and allowing for the flux of monomers between the thymosin-bound pool and F-actin.
Outside the brain, oxytocin-containing cells have been identified in several diverse tissues, including in females in the corpus luteum and the placenta; in males in the testicles' interstitial cells of Leydig; and in both sexes in the retina, the adrenal medulla, the thymus and the pancreas. The finding of significant amounts of this classically "neurohypophysial" hormone outside the central nervous system raises many questions regarding its possible importance in these different tissues.
Cardiac effects: oxytocin and oxytocin receptors are also found in the heart in some rodents, and the hormone may play a role in the embryonal development of the heart by promoting cardiomyocyte differentiation. However, the absence of either oxytocin or its receptor in knockout mice has not been reported to produce cardiac insufficiencies.
Advice & Tips: 5-HTP is a serotonin precursor. Serotonin is well-known as a hormone that affects one's mood in a positive way, but it is probably less-well known that it increases intestinal motility. It has worked magic for my symptoms. I am completely regular now, and the majority of my days are good days, whereas before I began taking it the majority of my days were bad days that began with symptoms of constipation and intestinal pain or discomfort. For me, at least, this is not a prescription. I began taking 5-HTP after my fiancee'--who had already been taking it to help her mood and, primarily, her difficulty sleeping through the night--learned it can be helpful when taken for gastrointestinal motility, and I began taking it myself shortly after that (and felt its effects almost immediately). Although not entirely unexpected, my slightly enhanced good moods are a nice side benefit of taking the supplement. I do get some very mild undesirable side effects, especially during mid-day when I take twice my morning and evening dose of 100 mg. Sometimes my face feels hot and flushes fairly noticeably--and this may be intensified with eating--but those symptoms subside within probably 30 minutes or less.
It bears understanding that this type of peptide is not a treatment or cure for anything, nor should it be considered a preventative measure to skin cancer. While this tanning peptide is known to protect the skin through the natural tanning process, it is not in and of itself a foolproof UV shield, however it is an excellent way for those who don't tan otherwise to get rich golden tans without as much exposure to the sun.
A Risk Quiz; Let’s say you are one of the volunteers to whom researchers gave $100, and this option: you can either keep the money, or give it to an anonymous trustee who will either invest it and double it to $200 and return half of the extra hundred bucks to you–$50–or keep all the money for herself. So you can either increase your money by 50%, or lose it all. What would you do? Would you trust that anonymous trustee? (Remember Loss Aversion from Chapter Two, where in a similar experiment most people decided to avoid the gamble and take the sure cash.)
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Drug interaction: Impact on effects of alcohol and other drugs: According to several studies in animals, oxytocin inhibits the development of tolerance to various addictive drugs (opiates, cocaine, alcohol), and reduces withdrawal symptoms. MDMA (ecstasy) may increase feelings of love, empathy, and connection to others by stimulating oxytocin activity primarily via activation of serotonin 5-HT1A receptors, if initial studies in animals apply to humans. The anxiolytic Buspar (buspirone) may produce some of its effects via 5-HT1A receptor-induced oxytocin stimulation as well.
There is no long-term side effects ever reported, but there is post injection effects while using Melanotan 2, typically these effects appear during the first few days of dosing and will become increasingly less obvious as the body adjusts to the peptide. These effects include: hot flush in face, mild nausea, decreased appetite, and increased sex drive. In order to combat nausea, an anti-histamine product can be taken until the body gets used to it. But most common way to deal with this is to take the dose before bed.
Tb4 has other effects that are needed in healing and repair of damaged tissue. It is a chemo-attractant for cells, stimulates new blood vessel growth (angiogenesis), downregulates cytokines and reduces inflammation, thus protecting newly formed tissue from damaging inflammatory events. Tb4 has been shown to reduce free radical levels (with similar efficiency as superoxide dismutase), decrease lipid peroxidation, inhibit interleukin 1 and other cytokines, and decrease inflammatory thromboxane (TxB2) and prostaglandin (PGF2 alpha).
In humans, oxytocin is thought to be released during hugging, touching, and orgasm in both genders. In the brain, oxytocin is involved in social recognition and bonding, and may be involved in the formation of trust between people and generosity.123 Oxytocin first became of interest to researchers when they discovered that breastfeeding women are calmer when exercising and experiencing stress than moms who were bottle-feeding. It is just one part of the important, complex neurochemical system in our bodies that helps us adapt to emotional situations.
Second, 5-HTP can cause serious drug interactions with many medications, especially those used to treat depression. Because antidepressants generally work by increasing serotonin in the brain, 5-HTP could combine with these medications to cause high concentrations of serotonin. Having too much serotonin can lead to serotonin syndrome, a serious condition characterized by dangerously high heart rate, blood pressure, and temperature. 5-HTP can interact with other classes of drugs, like migraine and pain medications, that also affect serotonin concentrations.
Showa Denko, the source of up to 60% of all the tryptophan sold in the United States, had used an untested manufacturing process that reduced the amount of activated charcoal used to filter fermented raw tryptophan. Some reports suggest that purity may be a potential problem for 5-HTP as well. No cases of EMS resulting from 5-HTP use have been reported, however.
Formulated Supplementary Sports Foods: The edible products sold on this site are not suitable for children under 15 years of age or pregnant women: Should only be used under medical or dietetic supervision. Contact your health-care provider immediately if you suspect that you have a medical problem. The food is not a sole source of nutrition and should be consumed in conjunction with a nutritious diet; and the food should be used in conjunction with an appropriate physical training or exercise program.
The full-length Tβ4 polypeptide has been shown to be effective in reducing inflammation . It is also reported that only the 4-AA, amino-terminal peptide of Tβ4, known as Ac-SDKP, can block inflammation . In this study, we used a synthetically human peptide produced copy of a naturally occurring, highly conserved 43-amino acid (MW = 4964 Da) water soluble acidic peptide, originally isolated from bovine thymus tissue . This peptide is produced by Fmoc solid-phase peptide synthesis in accordance with the current Good Manufacturing Practice (cGMP) regulations (21 CFR 210 and 211) of the FDA . An effective healer, Tβ4 can be administered topically on the surface of cells and systemically, through injection [9–11]. In this study, Tβ4 activation by Tβ4 peptide inhibited H2O2-induced production of NO and PGE2, expression of COX-2 and iNOS, and mRNA expression of TNF- α, IL-1β, -6, -8, and -17 in cultured PDLCs. These findings suggested that Tβ4 activation possessed anti-inflammatory activity in PDLCs. These results were consistent with previous in vivo and in vitro studies [9–15]. MAPK is a proline-directed serine/threonine kinase consisting of three-enzyme modules; its targets, inducing ERK, JNK and p38 kinases, are important in cellular signal transduction pathways and exert an anti-inflammatory response [48, 49]. NF-κB is a major transcription factor involved in the release of proteins that mediate the inflammatory response, and the degradation and phosphorylation of Iκ-Bα are necessary to release NF-κB from the cytoplasmic NF-κB/Iκ-Bα complex and allow its subsequent translocation to the nucleus of the cell . In this study, Tβ4 peptide down-regulated the H2O2-triggered activation of the ERK and JNK MAPKs and the NF-κB in PDLCs. These results suggested that the ERK and JNK MAPKs and the NF-κB pathway may be involved in the anti-inflammatory effects of Tβ4 activation in PDLCs. Consistent with our findings, Tβ4 treatment decreased TNF-α-induced NF-κB activation in human corneal epithelial cells .
When we asked a group of readers to test out 5-HTP to lose weight, they ate unlimited portions of healthy food and still shed up to five pounds in a week. We also talked to women who’d been using 5-HTP long term. Heather Miars started taking 5-HTP for her mood at Dr. Bhatia’s urging. “I was finally able to go off prescription antidepressants and lose 15 pounds!” recalls the 45-year-old mom. Meanwhile, Audra Holmes tried 5-HTP after developing “mood swings so wild, I was giving people whiplash,” she jokes. On 5-HTP, she says: “I didn’t have the highs and lows. I could suddenly get through the day without naps or comfort food!” She shed 50 pounds in 16 weeks. Wish you could have the same kind of success with an easy way to lose weight? As Dr. Oz put it: “5-HTP may be your pre-meal must-have!”
TBI patients frequently suffer from long-term deficits in cognitive and motor performance. No single animal model can adequately mimic all aspects of human TBI owing to the heterogeneity of clinical TBI.11 Some features of cognitive and motor function in humans have been successfully demonstrated in experimental brain trauma models.28-30 The controlled cortical impact (CCI) model is one of the most widely used TBI models. The CCI-TBI model has many clinically relevant features in that CCI causes not only cortical damage but also selective neuronal death in the hippocampus in rodents, leading to sensorimotor dysfunction and spatial learning and memory deficits, respectively.18,31-33
Supplements haven't been tested for safety and due to the fact that dietary supplements are largely unregulated, the content of some products may differ from what is specified on the product label. Also keep in mind that the safety of supplements in pregnant women, nursing mothers, children, and those with medical conditions or who are taking medications has not been established. You can get tips on using supplements, but if you're considering the use of 5-HTP supplements, talk with your primary care provider first. Self-treating a condition and avoiding or delaying standard care may have serious consequences.
Oxytocin produces antidepressant-like effects in animal models of depression, and a deficit of it may be involved in the pathophysiology of depression in humans. The antidepressant-like effects of oxytocin are not blocked by a selective antagonist of the oxytocin receptor, suggesting that these effects are not mediated by the oxytocin receptor. In accordance, unlike oxytocin, the selective non-peptide oxytocin receptor agonist WAY-267,464 does not produce antidepressant-like effects, at least in the tail suspension test. In contrast to WAY-267,464, carbetocin, a close analogue of oxytocin and peptide oxytocin receptor agonist, notably does produce antidepressant-like effects in animals. As such, the antidepressant-like effects of oxytocin may be mediated by modulation of a different target, perhaps the vasopressin V1A receptor where oxytocin is known to weakly bind as an agonist.
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.
So far, few studies have definitively linked autism to problems in oxytocin signalling. Some of the clearest evidence emerged in February, from a team led by neurogeneticist Daniel Geschwind of the University of California, Los Angeles. The group showed that mice that lacked a working copy of the Cntnap2 gene — which has been implicated in a small subset of human autism cases — had fewer oxytocin-containing neurons in the hypothalamus and socialized less with other mice than did control mice15. After receiving doses of oxytocin every day for two weeks, the mice behaved normally again. “Until this, there was no evidence that there was a subtype of autism that had to do with oxytocin deficits,” Geschwind says.
In the hypothalamus, oxytocin is made in magnocellular neurosecretory cells of the supraoptic and paraventricular nuclei, and is stored in Herring bodies at the axon terminals in the posterior pituitary. It is then released into the blood from the posterior lobe (neurohypophysis) of the pituitary gland. These axons (likely, but dendrites have not been ruled out) have collaterals that innervate neurons in the nucleus accumbens, a brain structure where oxytocin receptors are expressed. The endocrine effects of hormonal oxytocin and the cognitive or behavioral effects of oxytocin neuropeptides are thought to be coordinated through its common release through these collaterals. Oxytocin is also produced by some neurons in the paraventricular nucleus that project to other parts of the brain and to the spinal cord. Depending on the species, oxytocin receptor-expressing cells are located in other areas, including the amygdala and bed nucleus of the stria terminalis.
The RANKL and OPG have been identified as a key regulatory component of alveolar bone loss associated with inflammatory periodontal disease . Moreover, PDLCs were shown to express several osteoclastogenic cytokines, including both OPG and RANKL [30, 31]. Our data demonstrated that Tβ4 peptide abolished H2O2-induced RANKL expression and restored OPG expression. Osteoclasts, bone-resorptive multinucleated cells derived from hematopoietic stem cells, are associated with osteolytic diseases. Furthermore, NFATc1, a master modulator of osteoclastogenesis, regulates target genes, such as cathepsin K and calcitonin receptor or Calcr . In our in vitro study using BMMs, Tβ4 peptide directly and indirectly inhibited RANKL-induced osteoclast differentiation and expression of osteoclast markers, such as cathepsin-K, calcitonin receptor or Calcr, NFATc1, and RANK in BMM cells. These results indicated that Tβ4 was a key therapeutic target in controlling inflammation-induced bone loss.
Jump up ^ Hicks C, Ramos L, Reekie T, Misagh GH, Narlawar R, Kassiou M, McGregor IS (June 2014). "Body temperature and cardiac changes induced by peripherally administered oxytocin, vasopressin and the non-peptide oxytocin receptor agonist WAY 267,464: a biotelemetry study in rats". British Journal of Pharmacology. 171 (11): 2868–87. doi:10.1111/bph.12613. PMC 4243861. PMID 24641248.
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.
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 .
It should be noted that, anecdotally, 5-HTP is said to reduce cravings for carbohydrates in particular. The serotonergic (related to serotonin) system plays a role in macronutrient selection particular in obese persons with a craving for carbohydrates and enhancing serotonergic transmission is known to reduce these cravings. Beyond this, depressed serotonergic tranmission (hypothalamus) is also implicated in increased eating and reduced satiety in general.
In the ER, the patient's heart rate was elevated, she was sweaty, and had some muscle spasms. The physician in the ER called Poison Control for guidance. Poison Control indicated that a drug interaction between 5-HTP and Zoloft was a likely cause of the patient's symptoms because they were consistent with a rare but serious condition (serotonin syndrome) that occurs when serotonin concentrations in the brain are too high. Poison Control recommended a sedative to decrease the patient's heart rate and improve the other symptoms.
The following medications and other supplements may interact with 5-HTP. Effects may include increasing or decreasing sleepiness and drowsiness, interfering with the effectiveness of the medications or supplements, and interfering with the condition that is being treated by the medication or supplement. These are lists of commonly used medications and supplements that have scientifically identified interactions with 5-HTP. People who take these or any other medications and supplements should consult with a physician before beginning to use 5-HTP.