These studies demonstrate that in the animal model of TBI, early (6 hours post injury) treatment with Tβ4 i.p. at doses of 6 and 30 mg/kg reduces cortical lesion volume and hippocampal cell loss and improves functional recovery, suggesting its potential as a neuroprotective therapy for TBI. More importantly, delayed (24 hours post injury) treatment with Tβ4 administered i.p. at a dose of 6 mg/kg does not reduce lesion volume but significantly improves functional outcome in rats.34 Tβ4-induced angiogenesis, neurogenesis and oligodendrogenesis may contribute to functional recovery.34 Therefore, our data suggest that promoting endogenous neurorestorative processes using Tβ4 provides a novel therapeutic option for TBI. It should be noted that systemic administration of Tβ4 is safe and well-tolerated by animals and humans.26 Further investigation of the molecular mechanisms underlying Tβ4-mediated neuroprotection and neurorestoration is warranted.
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RegeneRX Biopharmaceuticals is focusing on the commercialization of Tb4 “For the treatment of injured tissue and non-healing wounds, to enable more rapid repair and/or tissue regeneration.” Especially needy are diabetics who suffer from poor blood circulation and loss of sensation of pain that keeps their wounds unnoticed and unattended for days, leading to ulcers that may not heal. Other hard healing wounds are pressure ulcers in patients who are bed ridden and often receive skin grafts as treatment, or reconstructive surgery.
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.”
Neurovascular units within the central nervous system consist of endothelial cells, pericytes, neurons and glial cells, as well as growth factors and extracellular matrix proteins that are close to the endothelium.72,73 Neurovascular units provide niches for neural stem/progenitor cells in the adult brain and, within these units, newly-generated immature neurons are closely associated with the remodeling vasculature. The generation of new vasculature facilitates several coupled neurorestorative processes including neurogenesis and synaptogenesis, which improve functional recovery.74-76 The vascular production of stromal-derived factor 1 and angiopoietin 1 is involved in neurogenesis and promotes behavioral recovery after stroke.77 The disruption of this neurovascular coordination has been observed in a variety of brain conditions including infection, stroke and trauma.78 The injured brain promotes angiogenesis and neurogenesis,13,32,69,79-84 that may contribute to spontaneous functional recovery from injuries such as stroke and TBI. Neurorestorative agents that increase angiogenesis and neurogenesis have been shown to improve functional outcome following brain injury.19,33 Vascular endothelial cells within the neurovascular niche affect neurogenesis directly via contact with neural progenitor cells, while soluble factors from the vascular system that are released into the CNS enhance neurogenesis via paracrine signaling.85 Here, we demonstrate that Tβ4 treatment promotes both angiogenesis and neurogenesis in rats after TBI, suggesting that the neurovascular remodeling at least partially contributes to Tβ4-mediated improvement in functional recovery. A better understanding of molecular mechanisms in the neurovascular niches will be important for developing novel angiogenic and neurogenic therapies for brain injuries.
5-HTP is POSSIBLY SAFE when taking by mouth appropriately. 5-HTP has been used safely in doses up to 400 mg daily for up to one year. However, some people who have taken it have developed a condition called eosinophilia-myalgia syndrome (EMS), a serious condition involving extreme muscle tenderness (myalgia) and blood abnormalities (eosinophilia). Some people think EMS might be caused by an accidental ingredient or contaminant in some 5-HTP products. However, there is not enough scientific evidence to know if EMS is caused by 5-HTP, a contaminant, or some other factor. Until more is known, 5-HTP should be used cautiously.
Another interesting agent reported to significantly accelerate chronic wound repair is infrared (700–1200 nm wavelength) and near infrared (600–700 nm) light delivered through lasers or light-emitting diodes (LEDs) (Mester et al., 1968; Rochkind et al., 1989; Conlan, 1996; Schindl et al., 2000; Enwemeka, 2004). Spectroscopic measurements indicate that photons at wavelengths of 630–800 nm penetrate through the skin and muscles of the forearm and lower leg (Chance et al., 1988; Beauvoit et al., 1994, 1995). The effect of the light may be to stimulate cytochrome c oxidase in the mitochondria, resulting in increased oxygen consumption and production of ATP (Karu, 1999).
As shown in Figure 1, thymic hormones also modulate the production of hypothalamus pituitary hormones and neuropeptides. Initial experiments revealed that neonatal thymectomy promotes a decrease in the number of secretory granules in acidophic cells of the adenopituitary . In the same vein, athymic nude mice display low levels of various pituitary hormones, such as PRL, GH, LH and FSH . With regard to thymic peptides, thymosin beta-4, when perfused intraventricularly, stimulates LH and LHRH secretion . Similar results were obtained with another thymic peptide, thymulin, in perfused or fragmented pituitary preparations . The administration of thymopoietin (another chemically-defined thymic hormone) in children with Hodgkin’s disease increased GH and cortisol serum levels . Moreover, thymopentin (the synthetic biologically active peptide of thymopoietin) enhances in vitro the production of ACTH and beta-endorphin . In addition, thymulin exhibits an in vitro stimulatory effect on perfused rat pituitaries, enhancing PRL, GH, TSH and LH release . Using short-term cultures of pituitary fragments, an increase in ACTH secretion occurs after in vitro thymulin addition, with no changes in GH levels and significant reductions in PRL release . A further thymosin peptide was recently isolated with the task in stimulating IL-6 release from rat glioma cells . By contrast, thymosin alpha-1 is apparently able to down regulate TSH, ACTH and PRL secretion in vivo with no modifications on GH levels . These inhibitory effects seem to occur through hypothalamic pathways. Indeed, the production of the corresponding releasing hormones by hypothalamic neurones decreased after in vitro addition of thymosin alpha-1 in medial basal hypothalamic fragments .
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.
In 19 obese females given either placebo or 8mg/kg (weight not actually given, only BMI between 30-40 for women) daily for 5 weeks without any concurrent dietary recommendations, 5-HTP treatment was associated with a decrease in appetite and food intake (resulting in weight loss) without significantly affecting mood state. This study noted that food intake was reduced from an average of 2,903kcal to 1,819kcal (62% of baseline) while placebo only reduced calories to 80%, and the 0.5kg weight loss in placebo was outperformed by a near 1.5kg loss in 5-HTP. These weight loss effects have been noted with 750mg 5-HTP over 2 weeks in overweight diabetics and over 12 weeks in obese persons given 900mg 5-HTP daily (58% of baseline intake); this latter study had a 6 week trial without a diet (in which significant weight loss was only noted at week 6) followed up by coadministration with a diet where weight loss proceeded to reach an additional 3.3kg over the subsequent 6 weeks; this latter study is duplicated in Medline.
New Turmeric+ with Ginger and Black Pepper. Each bottle of the enhanced Organic Turmeric+ contain 120 capsules with: 607mg turmeric,50mg ginger, 3mg black pepper for enhanced absorption and bioavailability. If you are sensitive to black pepper, you can still buy the original 100% organic turmeric capsules. Combine with Primal Collective Omega 3 EPA/DHA fats for enhanced absorption. Also add in the New...
In addition to angiogenesis and neurogenesis, cell- and pharmacologically based therapies substantially remodel white matter in the ischemic brain. Treatment of experimental stroke with MCSs, rhEPO, or sildenafil significantly increases axonal density encapsulating the ischemic lesion. Dynamic changes of white matter structure along the ischemic boundary have been imaged in living animals by diffusion tensor imaging (DTI) and fractional anisotropy (FA) measurements. Data from these MRI indices demonstrate that administration of rhEPO or sildenafil augments axonal remodeling and angiogenesis and that both of them are spatially and temporally correlated. Administration of MSCs, rhEPO, and thymosin beta 4 (Tβ4) dramatically increases the number of oligodendrocyte progenitor cells in the corpus callosum, the striatum, and the V/SVZ of the ischemic hemisphere and mature oligodendrocytes in the ischemic boundary adjacent to myelinated axons. These findings suggest that cell- and pharmacologically based therapies promote generation of oligodendrocyte progenitor cells in the ischemic brain that migrate to target axons, where they extend their processes myelinating the axons.
Thymosin beta(4), a small ubiquitous protein containing 43 aa, has structure/function activity via its actin-binding domain and numerous biological affects on cells. Since it is the major actin-sequestering molecule in eukaryotic cells and is found essentially in all cells and body fluids, thymosin beta(4) has the potential for significant roles in tissue development, maintenance, repair, and pathology. Several active sites with unique functions have been identified, including the amino-terminal site containing 4 aa (Ac-SDKP) that generally blocks inflammation and reduces fibrosis. Another active site at the amino terminus contains 15 aa, including Ac-SDKP, and promotes cell survival and blocks apoptosis, while a short sequence containing LKKTETQ, the central actin-binding domain (aa 17-23) plus 1 additional amino acid (Q), promotes angiogenesis, wound healing, and cell migration. Several additional biological activities have been identified but not yet localized in the molecule, including its antimicrobial activity, the induction of various genes (including laminin-5, MMPs, TGF beta, zyxin, terminal deoxynucleotidyl transferase, and angiogenesis-related proteins), and the ability to activate ILK/PINCH/Akt, and other signaling molecules important in both apoptosis and inflammatory pathways. This review details these important physiologically and pathologically active sites and their potential therapeutic uses.
Combined treatments of 5-HTP and SSRI seem to have strong synergistic effects on serotonin levels in rats and humans so that some clinicians recommend the use of slow-released 5-HTP in combination with SSRIs (R, R2, R3). However, additional clinical trials are required to demonstrate the safety and effectiveness of this approach, and combinations of 5-HTP and medications should only be used under medical supervision.
Hi Ben. Have a groin problem which I have had for years and it just won’t go away it’s not a hernia or osteitis pubis I had an MRI and the specialist said they wouldn’t operate. I can still play sport but I’m just less agile and slower than normal and it takes a few days for the groin pain to go away after sport. Would tb500 help to heal it or would bpc157 or something else be better? Thanks :)
I’ve used powdered 5-HTP a couple times now, it doesn’t taste great and it’s resulted in an unpleasant stomach upset that lasted 45–60 minutes. For that reason I’ll likely not continue to use it. I did not find it’s effect on mood remarkable enough that I would want to put up with the stomach upset. My go to Nootropics for mood are Rhodiola and Phenibut and my go to Biohacks for mood are meditation and no fap, I don’t feel the need to use a whole lot more mood promoting strategies.
The biologically active form of oxytocin, commonly measured by RIA and/or HPLC techniques, is also known as the octapeptide "oxytocin disulfide" (oxidized form), but oxytocin also exists as a reduced straight-chain (non-cyclic) dithiol nonapeptide called oxytoceine. It has been theorized that oxytoceine may act as a free radical scavenger, as donating an electron to a free radical allows oxytoceine to be re-oxidized to oxytocin via the dehydroascorbate / ascorbate redox couple.
Cells were pretreated with indicated concentrations of Tβ4 peptide for 2 hours, post-incubated with 200 μM H2O2 for 48 hours, and then conditioned medium (CM) was collected. Mouse BMMs were cultured with CM in the presence of M-CSF (30 ng/mL) and RANKL (100 ng/mL), as described in Materials and methods. After 5 days, cells were fixed and stained for TRAP as a marker of osteoclasts (A), and the number of TRAP-positive multinucleated cells (MNCs) was scored (B). TRAP osteoclast activity was assayed using the TRAP cytochemical stain technique (C). * Statistically significant differences compared with the control, p<0.05. The data presented were representative of three independent experiments.
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.
Despite these many roles, oxytocin is often reduced to a misleading label. While “hormone of love” may be great for catchy headlines and compelling marketing slogans, they are ultimately misleading. Jennifer Bartz from the Mount Sinai School of Medicine has found that oxytocin can have completely opposite effects on the way people behave, depending on how they view their relationships to other people.
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.
Jump up ^ Venkatesh B, Si-Hoe SL, Murphy D, Brenner S (November 1997). "Transgenic rats reveal functional conservation of regulatory controls between the Fugu isotocin and rat oxytocin genes". Proceedings of the National Academy of Sciences of the United States of America. 94 (23): 12462–6. Bibcode:1997PNAS...9412462V. doi:10.1073/pnas.94.23.12462. PMC 25001. PMID 9356472.
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.
Again, the three groups of mice were exposed to the stressful experience of social defeat in the cages of other more aggressive mice. This time, six hours after the social stress, the mice were put in a box in which they received a brief electric shock, which startles them but is not painful. Then 24 hours later, the mice were returned to the same box but did not receive a shock.
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.
5-HTP has been shown in scientific studies to promote relaxation and alleviate stress and anxiety. The relaxation and anti-anxiety properties of 5-HTP appear to come from its ability to elevate levels of serotonin. Research has demonstrated that 5-HTP may reduce the risks of panic attacks and symptoms of panic, as well as anxiety and emotional stress. Research also indicates 5-HTP may be effective in helping to alleviate depression.
Naturalistic studies like ours can help unravel the evolutionary history and function of these hormones. Basically, the fact that hormone mechanisms have been tweaked during evolution suggests that the behaviors they promote have provided fitness benefits in the past. In this case, hunting and sharing meat must have increased men’s reproductive success.
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 .
Melanotan II is a synthetic hormone that speeds up the production of melanin, the pigment that absorbs ultraviolet radiation and gives skin its colour. It was originally developed as a potential treatment for female sexual dysfunction and erectile dysfunction, but this research ceased in 2003. In technical terms, Melanotan II is a synthetic analogue of the peptide hormone α-melanocyte-stimulating hormone (α-MSH). Today, there are numbers of sellers on the internet of unlicensed and untested powders sold as Melanotan II.
Ive been struggling with my left brachialis and so after listening to a podcast in which you mentioned BPC-157 I tried it out. I was hoping for a miracle cure, which I did not get. However, I believe it certainly helped a lot. I am considering a second round. But the peptide rabbit hole is certainly interesting and I am most keen to try some others. But I would like to see if you have some advise for me on another topic. After having listened to your podcast with Dr Gains I thought that either you or Dr Gains may be able to at least point me in the right direction. My wife suffers from a condition called Pelvic Vein Congestion which causes her a lot of pain. From what I understand, she has a seemingly unnatural mass of veins around her uterus which may also suffer from a “valve” type problem in which blood can potentially run in the opposite direction and pool in locations which causes pain. She has been to doctors which offer invasive solutions with unattractive success rates. I have been searching for other cures, but the only thing that I found (supplement with Diosmin and Hisperidan) had some psychological effects. Any thoughts?
Beta thymosins are a family of proteins which have in common a sequence of about 40 amino acids similar to the small protein thymosin β4. They are found almost exclusively in multicellular animals. Thymosin β4 was originally obtained from the thymus in company with several other small proteins which although named collectively "thymosins" are now known to be structurally and genetically unrelated and present in many different animal tissues.
5-HTP works in the brain and central nervous system by increasing the production of the chemical serotonin. Serotonin can affect sleep, appetite, temperature, sexual behavior, and pain sensation. Since 5-HTP increases the synthesis of serotonin, it is used for several diseases where serotonin is believed to play an important role including depression, insomnia, obesity, and many other conditions.