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).
In addition to its intracellular role as the major actin-sequestering molecule in cells of many multicellular animals, thymosin β4 shows a remarkably diverse range of effects when present in the fluid surrounding animal tissue cells. Taken together, these effects suggest that thymosin has a general role in tissue regeneration. This has suggested a variety of possible therapeutic applications, and several have now been extended to animal models and human clinical trials.
During clinic trials for its use as a tanning agent, melanotan II was found to be a potent stimulator of male erections. A new drug based on melanotan II, bremelanotide, was developed to take advantage of this property. It has been noted across several studies to increase rigidity and duration of male erection, as well as male sexual desire. It has also been shown to increase female sexual desire in patients with sexual arousal disorder.
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.
Autism: Oxytocin has been implicated in the etiology of autism, with one report suggesting autism is correlated with genomic deletion of the gene containing the oxytocin receptor gene (OXTR). Studies involving Caucasian and Finnish samples and Chinese Han families provide support for the relationship of OXTR with autism. Autism may also be associated with an aberrant methylation of OXTR.
To further determine the potential anti-inflammatory effects of Tβ4 activation, expressions of proinflammatory or osteoclastogenic cytokines were measured by RT-PCR (Fig 4A). The TNF-α, IL-1β, IL-6, IL-8, and IL-17 mRNA levels increased in the H2O2- stimulated PDLCs, and these increases were significantly decreased in a concentration-dependent manner by treatment with the Tβ4 peptide. Since receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) are two important osteoclastogenic factors, we next explored the effects of Tβ4 peptide on RANKL and OPG expressions in PDLCs. Tβ4 peptide reduced H2O2-stimulated up-regulation of RANKL, with a reciprocal increase in OPG mRNA in a dose-dependent manner (Fig 4B).
This may be an odd question. But would this be good to inject or spray on those that have undergone hair transplants in the first month of surgery. Fue microscars. I see you mention it improves hair growth and blood flow. both which basically what rogaine claims to do. Surely this would benefit new transplanted hair follicles in taking and holding? Interested in your thoughts in the matter.
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It would have been interesting if Bartz had asked about *both* parents’ parenting styles. (Spoken by a guy writing a book on fathers.) It would have been easy enough; just add another question. Any differences between perceptions of mothers and fathers might have been illuminating. But, as in so much family research, fathers were once again ignored or excluded. (As if fathers don’t have parenting styles…)
I have Dupretren’s in my hand. The chords are tightening which is common to this disease pulling the fingers towards the palm. I cannot play guitar any longer. I can still hold a flat palm to the floor when I exercise, but it gets more difficult as the disease takes hold (no pun intended). I’ve read a lot from others inflicted with this. Didn’t like what I read. Hand surgery with modest effects, often adverse effects and too infrequent a fix to the problem. I tried deep tissue massage and scraping too.
Jump up ^ Ballweber E, Hannappel E, Huff T, Stephan H, Haener M, Taschner N, Stoffler D, Aebi U, Mannherz HG (Jan 2002). "Polymerisation of chemically cross-linked actin:thymosin beta(4) complex to filamentous actin: alteration in helical parameters and visualisation of thymosin beta(4) binding on F-actin". Journal of Molecular Biology. 315 (4): 613–25. doi:10.1006/jmbi.2001.5281. PMID 11812134.
FGF-2 and VEGF enhance angiogenesis in chronic wounds (Greenalgh, 1996; Kirchner et al., 2003). Thymosin β-4 increases angiogenesis, consistent with its ability to induce epicardial cells to differentiate into endothelial and smooth muscle cells of coronary vessels (Chapter 7). L-arginine enhances angiogenesis in chronic wounds by enhancing the production of endothelial nitric oxide and improving blood flow (Shi et al., 2003). L-arginine also plays a role in the formation of proline, which is essential for the structure of collagen molecules. ChrysalinTM, a synthetic peptide representing the portion of human thrombin that binds to the surface of endothelial cells, doubled the incidence of complete healing of diabetic foot ulcers in human patients (Fife et al., 2007). Another molecule used to treat peripheral artery disease, pentoxifylline, was reported to improve blood flow in chronic wounds by reducing blood viscosity (Falanga et al., 1999).
^ Jump up to: a b Hurlemann R, Patin A, Onur OA, Cohen MX, Baumgartner T, Metzler S, Dziobek I, Gallinat J, Wagner M, Maier W, Kendrick KM (April 2010). "Oxytocin enhances amygdala-dependent, socially reinforced learning and emotional empathy in humans". The Journal of Neuroscience. 30 (14): 4999–5007. doi:10.1523/JNEUROSCI.5538-09.2010. PMID 20371820.
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 .
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.
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.
5-HTP is very reliable in increasing serotonin levels. 5-HTP is actually used as a clinical test to judge the potency of drugs that affect serotonin levels (by pairing an experimental drug with 5-HTP to induce 'serotonin syndrome', or serotonin toxicity, one can see how much that drug exacerbates serotonin biosynthesis or bioavailability by seeing how much of a 5-HTP dose is required to induce the syndrome; the lower dose indicative of higher drug potency). This test is known as the 5-HTP induced syndrome test.
Mouse BMMs were cultured with M-CSF (30 ng/mL) and RANKL (100 ng/mL) or CM collected from PDLCs for 5 days (A) and 60 minutes (B). The mRNAs expression was determined by PCR analysis (A). The phosphorylation of MAPKs (p38, JNK, and ERK), and activation of NF-κB were determined by Western blot analysis (B). Data were representative of three independent experiments. 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.
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.
I went to a neurologist, He said it was just in my head because I have depression–the exact reason why I took 5HTP. Not satisfied with that doctor, I went to an immunologist. He said I got myositis. Eosinophilic Myositis. From my blood test, I got positive ANA IF, very high number of IgE, elevated Creatine Kinase, and very low Vitamin D 25(OH)D. But my ANA Profile test showed negative.
When combined with antidepressants of the MAOI or SSRI class, very high parenteral doses of 5-HTP can cause acute serotonin syndrome in rats. It is unclear if such findings have clinical relevance, as most drugs will cause serious adverse events or death in rodents at very high doses. In humans 5-HTP has never been clinically associated with serotonin syndrome, although 5-HTP can precipitate mania when added to an MAOI.