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.
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 .
The combination of supplemental 5-HTP and a dopamine decarboxylase inhibitor is also thought to reduce the risk for cardiovascular complications, as excess serum (but not neural) serotonin is associated with heart valve disease in rats. Due to the accumulation of 5-HTP in neural tissue following the combination it is plausible to assume a reduction in systemic serotonin; this has not been demonstrated yet, however.
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.”
“I didn’t think it would be that bad honestly, but since I weight lift multiple times a weak, this supplement is doing me more harm than good. On a typical weight lifting day my workout is split into 5 sections. After taking 5-htp the night before I barely have enough energy to get through 1 section, and that is a serious problem, because of this I am quitting 5-htp all together.”
A critical step in wound healing is angiogenesis. New vessels are needed to supply nutrients and oxygen to the cells involved in repair, to remove toxic materials and debris of dead cells and generate optimal conditions for new tissue formation. Another important step is the directional migration of cells into the injured area, joining up to repair the wound. This requires an attractant that will direct the cells to the wound and propel them to the site. These critical steps in wound healing are regulated by beta 4, as seen in the following experiments.
In all groups, [intravenous tryptophan] impaired memory and psychomotor performance significantly. In conclusion, cognitive deficits in [bipolar patients] following [intravenous tryptophan] may reflect a central 5-HT vulnerability in frontal brain areas. Independent of [intravenous tryptophan], cognitive deficits in [bipolar patients] provide evidence for a trait marker for [bipolar disorders].
Melanotans include melanotan I (afamelanotide) and melanotan II. Both melanotan I and II are widely abused to obtain a cosmetic tan. The melanotans are potent, non-selective melanocortin receptor agonists affecting MC1, MC3, MC4 and MC5 receptors. These receptors are responsible for many physiological systems including: pigmentation, energy, sexual function, immune system, inflammation and the cardiovascular system.
The reality is that people are always going to self-medicate. Boots, Amazon and H&B all sell 5-HTP, and in theory you could keep buying it and taking it for as long as you like. But it's important to know the facts. It shouldn't be used in conjunction with an SSRI, for example. In that situation, if the body is preventing serotonin breakdown while also getting extra serotonin, which leads to seriously unhealthy levels of serotonin activity.
Exposure to ultraviolet (UV) light prompts an increased release of Alpha-MSH, which in turn stimulates the production of melanin in the skin. The more melanin produced the greater pigmentation level becomes, making the skin progressively darker and tan lasts significantly longer. This makes Melanotan peptide unique, people do not require as much exposure to UV light to produce more melanin, very attractive for people wishing to develop greater tanning of the skin in fastest way possible.
To determine the effects of Tβ4 peptide and H2O2 on cytotoxicity, its cell viability was evaluated. A 48-h exposure to 0.1–5 μg/mL Tβ4 peptide did not affect H2O2-mediated cell viabilities (Fig 2A). In order to examine whether Tβ4 peptide suppressed ROS-induced inflammatory mediators, the ability of Tβ4 peptide on production of NO and PGE2, and expressions of COX-2 and iNOS were measured by RT-PCR, Western blot, and ELISA. Pretreatment with Tβ4 peptide dose-dependently inhibited H2O2-induced mRNA and protein expressions of COX-2 and iNOS, and NO and PGE2 production (Fig 2B–2E).
Astrocytes constitute the largest population of cells in the central nervous system, constituting approximately 90% of human parenchymal cells. Astrocytes are highly responsive to injury, undergoing rapid hyperplasia and hypertrophy. Astrocytes act as physical and biochemical barriers to axonal regeneration by forming glial scars along ischemic lesions and producing axonal growth-inhibitory proteoglycans. Administration of MSCs significantly attenuates the glial scar in the ischemic boundary and reduces expression of inhibitory proteins, such as Nogo. Analysis of single-cell astrocytes isolated from the ischemic boundary by laser capture microdissection reveals that administration of MSCs dramatically down regulates neurocan, an axonal growth-inhibitory proteoglycan. Coculture of MSCs with astrocytes also substantially reduces neurocan expression in astrocytes activated by oxygen glucose deprivation. These findings suggest that injected MSCs reduce physical and biochemical barriers of astrocytes, which also contribute to axonal and neurite outgrowth.
Uterine contraction important for cervical dilation before birth and causes contractions during the second and third stages of labor. Oxytocin release during breastfeeding causes mild but often painful uterine contractions during the first few weeks of lactation. This also serves to assist the uterus in clotting the placental attachment point postpartum. However, in knockout mice lacking the oxytocin receptor, reproductive behavior and parturition is normal.
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.
Delayed Tβ4 treatment increases vascular density in the injured cortex, ipsilateral dentate gyrus, and CA3 region 35 days after TBI. Arrows show vWF-stained vascular structure. TBI alone (B) significantly increases the vascular density in the injured cortex compared to sham controls (A, P < 0.05). Tβ4 treatment (C) further enhances angiogenesis after TBI compared to the saline-treated groups (P < 0.05). The density of vWF-stained vasculature in different regions is shown in (D). Scale bar = 25 μm (C). Data represent mean + SD. *P < 0.05 vs Sham group. #P < 0.05 vs Saline group. N (rats/group) = 6 (Sham); 9 (Saline); and 10 (Tβ4).
The polyherbal formula described for acute wounds promoted both angiogenesis and fibroblast proliferation and collagen synthesis in a streptozotocin diabetic rat model (Gupta et al., 2008). Dressings impregnated with copper oxide applied to wounds of diabetic mice resulted in the upregulation of the pro-angiogenic factors placental growth factor, hypoxia-inducible factor-1α and VEGF, leading to increased angiogenesis and faster wound closure (Borkow et al., 2010). High-throughput screening of medicinal plants known to be beneficial for blood circulation identified a material named SBD.4a from the plant Angelica sinensis as having angiogenic properties on a par with PDGF-BB (Zhao et al., 2006).
There have been some side effects reported 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: nausea, appetite loss, drowsiness and increased sex drive. In order to combat nausea, an anti-histamine can be taken when injecting until the body gets used to it. But most common way to deal with this is to inject Melanotan before bed, this is also beneficial to combat any drowsiness.
There is also a positive feedback involved in the milk-ejection reflex. When a baby sucks at the breast of its mother, the stimulation leads to oxytocin secretion into the blood, which then causes milk to be let down into the breast. Oxytocin is also released into the brain to help stimulate further oxytocin secretion. These processes are self-limiting; production of the hormone is stopped after the baby is delivered or when the baby stops feeding.
The enzyme dopamine decarboxylase (aromatic L-amino acid decarboxylase) mediates the conversion of 5-HTP into serotonin, and this enzyme is expressed in stomach tissue. Inhibition of this enzyme in the stomach during 5-HTP ingestion is thought to promote the concentration of 5-HTP that reaches neural tissue, which is supported by a study using 100-200mg Carbidopa (pharmaceutical inhibitor) alongside 5-HTP to increase radioactivity of 5-HTP (indicative of neural accumulation) in humans.
Chae, H. S., Kang, O. H., Choi, J. G., Oh, Y. C., Lee, Y. S., Jang, H. J., Kim, J. H., Park, H., Jung, K. Y., Sohn, D. H., and Kwon, D. Y. 5-hydroxytryptophan acts on the mitogen-activated protein kinase extracellular-signal regulated protein kinase pathway to modulate cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW 264.7 cells. Biol Pharm Bull 2009;32:553-557. View abstract.
Six hours later, the mice were returned to cages with the aggressive mice. The mice that were missing their oxytocin receptors didn't appear to remember the aggressive mice and show any fear. Conversely, when mice with increased numbers of oxytocin receptors were reintroduced to the aggressive mice, they showed an intense fear reaction and avoided the aggressive mice.
Thymosin beta 4 is a small 43 amino acid protein (a peptide) that was originally identified in calf thymus, an organ that is central in the development of immunity. Tb4 was later found in all cells except red blood cells. It is highest in blood platelets that are the first to enter injured areas, in wound healing. Tb4 is also detected outside cells, in blood plasma and in wound and blister fluids.
Jump up ^ Vargas-Pinilla P, Paixão-Côrtes VR, Paré P, Tovo-Rodrigues L, Vieira CM, Xavier A, Comas D, Pissinatti A, Sinigaglia M, Rigo MM, Vieira GF, Lucion AB, Salzano FM, Bortolini MC (January 2015). "Evolutionary pattern in the OXT-OXTR system in primates: coevolution and positive selection footprints". Proceedings of the National Academy of Sciences of the United States of America. 112 (1): 88–93. Bibcode:2015PNAS..112...88V. doi:10.1073/pnas.1419399112. PMC 4291646. PMID 25535371.
Don't be surprised. A lot of people haven't heard of Melanotan. Melanotan is a tanning peptide that stimulates the production of melanin in the body to foster a deep, natural tan. This is the body's way of protecting itself from too much sun exposure by increasing the level of melanin in the body. Melanin is your body's natural response to UV damage. The end result is a darkening of the skin.
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
This mother-child bonding is the most glorified myth that is not re-thought as often as it should. Its apparant purpose is just to make a dangerously selfish mother (such frustrated mothers do exist a lot more than we read in the news) to think twice before harming her defenseless child which is oftentimes in her sole custody in our society. Acts of such mothers are branded as mental illness rather than plain cruelty. While most people (men and women alike) tend to protect, and not harm a child, the real bonding can happen beetween two independent, mature adults.
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.
Hey mate, I’m getting a shoulder reconstrcution in about 2 weeks. Do you think that TB-500 and BPC-157 would help heal something as complex as this. Or do you think that stacking something like GHRP-6 and CJC-1295 would work better because this would assist in muscle growth and strength gains of surrounding muscles etc. Also if chose to use peptides when do you think I should start using them, I will be in a sling for 6weeks after surgery with only passive movements.
Bone loss associated with inflammatory diseases, such as rheumatoid arthritis, periodontal disease, and osteoporosis, and elevated osteoclast activity leads to bone destruction . The most common osteolytic disease, periodontitis, is a multi-factorial irreversible and cumulative condition, initiated and propagated by bacteria and host factors . Destruction of peridontal tissue is mediated via the expression of various tissue-destructive enzymes or inflammatory mediators such as interleukins-1 (IL-1), IL-6 and IL-8, tumor necrosis factor- α (TNF- α), nitric oxide (NO), and prostaglandin E2 (PGE2) . Receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL) and osteoprotegerin (OPG) are critical for homeostatic control of osteoclast activity, suggesting that they have vital roles in the progression of bone loss in periodontitis [3, 4]. Therefore, resolution of inflammation and blocking osteoclast differentiation might be a potential therapeutic approach for the prevention and treatment of osteolytic inflammatory disease, such as periodontitis .
I’ve been on this stuff for lots of years. I really needed it when I was depressed like hell, and I had an emotional pain that simply didn’t go away for 2 decades prior to starting that stack. Did it help? yes. Was it the best intervention possible? probably not. I was able to get off all this stuff with the uridine stack, and I believe it partly fixed a part of my brain that was damaged from this decade long suffering. So this is, why I am now more into brain regeneration and psychotherapeutic interventions (even though I do them myself), and I would only go back to this stack if I was completely fucked up again. There are a lot of side effects, and its a fine line to balance the supplements, to get rid of the side effects…
The oxytocin peptide is synthesized as an inactive precursor protein from the OXT gene. This precursor protein also includes the oxytocin carrier protein neurophysin I. The inactive precursor protein is progressively hydrolyzed into smaller fragments (one of which is neurophysin I) via a series of enzymes. The last hydrolysis that releases the active oxytocin nonapeptide is catalyzed by peptidylglycine alpha-amidating monooxygenase (PAM).
Do I have to diet? Studies show that 5-HTP enhances weight loss even if you continue eating your normal foods. Without a diet, you stand to lose about a pound a week; many folks eventually drop 15 pounds or more without dieting. Of course, taking 5-HTP to lose weight works by lowering caloric intake — and the more calories you cut, the more you’ll lose. So if you want to maximize results, try tweaking your diet at the two-week mark, when 5-HTP will have fully kicked in, diminishing hunger and carb cravings. Below, we’ve got a version of the diet used in one university study that helped 5-HTP takers lose several times more weight than folks getting a placebo.
At least one study using an extract of Griffonia simplicifolia (10.24mg giving 2.56mg 5-HTP; confounded with Centella asiatica and Taraxacum officinale at 11.7mg and 4.55mg Paulina cupana and 9.75mg Artichoke extract) taken in three hits, five times a day (40mg 5-HTP total), by 20 overweight or obese females (non-depressive and without eating disorders) for 4 weeks has noted an increase in satiety and reduced binge eating tendencies; the increase in satiety was said to account for the improved weight loss results seen in the experimental group when both were given weight loss advice and diets. This spray has been noted elsewhere to increase satiety (and vicariously through that, body weight) over 2 months in a similar demographic of women.
Stimulation of milk ejection (milk letdown): Milk is initially secreted into small sacs within the mammary gland called alveoli, from which it must be ejected for consumption or harvesting. Mammary alveoli are surrounded by smooth muscle (myoepithelial) cells which are a prominant target cell for oxytocin. Oxytocin stimulates contraction of myoepithelial cells, causing milk to be ejected into the ducts and cisterns.
Growth factors play an important role is enhancing structural repair of chronic wounds (Robson, 1997). KGF-2 (Robson et al., 2001), TGF-β (Robson et al., 1995), PDGF-BB (Mustoe et al., 1994; Kiritsy et al., 1995; Smiell et al., 1999), β-NGF (Muangman et al., 2004) have been shown to enhance re-epithelialization (Greenalgh, 1996 for review). The KGF-1 gene has been shown to improve cutaneous wound healing in a septic rat model when delivered in a plasmid (Lin et al., 2006). The PDGF-B gene carried in a plasmid mixed with a bovine collagen gel was reported to accelerate closure of patient diabetic ulcers (Mulder et al., 2009; Blume et al., 2011). KGF-2, PDGF-BB and FGF-L are commercially available as RepiferminTM, RegranexTM, and Trafermin to treat human chronic wounds. Data for the effects of PDGF-BB on back wounds of diabetic mice and for the effects of KGF-2 on chronic venous ulcers in patients is tabulated in Tables 10.3 and 10.4. Thymosin β4 accelerated keratinocyte migration in the wounds of old diabetic mice (Philp et al., 2003).
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.
Jump up ^ Gauquelin G, Geelen G, Louis F, Allevard AM, Meunier C, Cuisinaud G, Benjanet S, Seidah NG, Chretien M, Legros JJ (1983). "Presence of vasopressin, oxytocin and neurophysin in the retina of mammals, effect of light and darkness, comparison with the neuropeptide content of the neurohypophysis and the pineal gland". Peptides. 4 (4): 509–15. doi:10.1016/0196-9781(83)90056-6. PMID 6647119.
The first study to show that Tβ4-promoted tissue repair was a dermal study performed in rats (Malinda et al., 1999). It had previously been found to promote angiogenesis and was reported to be high in platelets (Grant et al., 1995; Hannappel & van Kampen, 1987; Malinda, Goldstein, & Kleinman, 1997; Philp, Huff, Gho, Hannappel, & Kleinman, 2003). Since platelets are the first cells to enter a wound, it was clear that Tβ4 should be tested in dermal wounds in an animal model (Malinda et al., 1997, 1999; Philp, Badamchian, et al., 2003). In the first dermal study using 8 mm full-thickness punch wounds in rats, Tβ4 at 5 μg/50 μL of phosphate-buffered saline was found to accelerate wound closure, increase angiogenesis, and accelerate collagen deposition (Malinda et al., 1999). Tβ4 was only applied at the time of injury and at 48 h since after that the crust had formed. Visible macroscopic improvement was seen in the treated group by day 4. The study also found that Tβ4 promoted keratinocyte migration in vitro with activity in the picogram range. The findings were confirmed in various additional animal models (Table 1) and led to the clinical trials for hard to heal wound in patients as detailed in Table 2.
This is a great product, I have been having digestive problems after 13 major surgeries and suffering from Crohn's Disease my whole life. Currently I can only tolerate a liquid diet. Was very depressed, found this and started taking it and it has made a HUGE difference to my life. Only have very mild depression symptoms now, and sleep better at night. Bought the powder to get the dose right, looks like 100mg suits my 50 kg frame. Only bad thing is the packaging. The 10 grams of powder is lost in the large packet, very hard to get it out and measure the same dose every night. I purchased miniature measuring spoons from ebay and they make life much easier. Sort out the correct spoon for your dosage with the scales then off you go. Can be tricky getting it in and out of the bag, often get powder everywhere, but usually just lick it off. A pill container would work much better for this power.
Down syndrome. Some research shows that giving 5-HTP to infants with Down syndrome might improve muscle and activity. Other research shows that it does not improve muscle or development when taken from infancy until 3-4 years of age. Research also shows that taking 5-HTP along with conventional prescription drugs does improve development, social skills, or language skills.