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.)
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.
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.
Treatment with thymosin beta 4 (Tβ4) reduces infarct volume and preserves cardiac function in preclinical models of cardiac ischemic injury. These effects stem in part from decreased infarct size, but additional benefits are likely due to specific antifibrotic and proangiogenic activities. Injected or transgenic Tβ4 increase blood vessel growth in large and small animal models, consistent with Tβ4 converting hibernating myocardium to an actively contractile state following ischemia. Tβ4 and its degradation products have antifibrotic effects in in vitro assays and in animal models of fibrosis not related to cardiac injury. This large number of pleiotropic effects results from Tβ4’s many interactions with cellular signaling pathways, particularly indirect regulation of cellular motility and movement via the SRF–MRTF–G-actin transcriptional pathway. Variation in effects and effect sizes in animal models may potentially be due to variable distribution of Tβ4. Preclinical studies of PK/PD relationships and a reliable pharmacodynamic biomarker would facilitate clinical development of Tβ4.
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.
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.
Tβ4 was down-regulated in H2O2-exposed PDLCs in dose- and time-dependent manners. Tβ4 activation with a Tβ4 peptide attenuated the H2O2-induced production of NO and PGE2 and up-regulated iNOS, COX-2, and osteoclastogenic cytokines (TNF-α, IL-1β, IL-6, IL-8, and IL-17) as well as reversed the effect on RANKL and OPG in PDLCs. Tβ4 peptide inhibited the effects of H2O2 on the activation of ERK and JNK MAPK, and NF-κB in PDLCs. Furthermore, Tβ4 peptide inhibited osteoclast differentiation, osteoclast-specific gene expression, and p38, ERK, and JNK phosphorylation and NF-κB activation in RANKL-stimulated BMMs. In addition, H2O2 up-regulated Wnt5a and its cell surface receptors, Frizzled and Ror2 in PDLCs. Wnt5a inhibition by Wnt5a siRNA enhanced the effects of Tβ4 on H2O2-mediated induction of pro-inflammatory cytokines and osteoclastogenic cytokines as well as helping osteoclastic differentiation whereas Wnt5a activation by Wnt5a peptide reversed it.
I have done my research related to this, I am thinking about ordering TB-500…I have a few questions to ask before ordering, I am a volleyball player and stopped playing for a while to let it rest and in process of healing. I have A SLAP tear is an injury to the labrum of the shoulder. Should I use TB-500 for shoulder so it can increase muscle growth? I would be interested on your take of how to do the injections there.
This anti-social effect of a social hormone brings some nuance to the story of oxytocin. In one study, researchers found that Dutch students given a snort of the hormone became more positive about fictional Dutch characters, but were more negative about characters with Arab or German names. The finding suggests that oxytocin's social bonding effects are targeted at whomever a person perceives as part of their in-group, the researchers reported in January 2011 in the journal PNAS.
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).
In the prairie vole, oxytocin released into the brain of the female during sexual activity is important for forming a pair bond with her sexual partner. Vasopressin appears to have a similar effect in males. Oxytocin has a role in social behaviors in many species, so it likely also does in humans. In a 2003 study, both humans and dog oxytocin levels in the blood rose after five to 24 minutes of a petting session. This possibly plays a role in the emotional bonding between humans and dogs.
In some studies that record appetite suppression with 5-HTP supplementation, nausea appears to also be reported at higher freqencies than placebo, although some interventions note this as the only relevant side effect. Short term studies tend to note that nausea persists throughout the study period while those expanding beyond three weeks note that reports of nausea tend to decline at this time point.
Recently, therapeutic biomolecules such as growth factors provide great potential as an alternative therapeutic approach to traditional periodontal wound healing . However, because of the short half-lives of growth factors and polynucleotides in the body and the necessity to deliver to specific target sites, those medicinal substances do not always exhibit the anticipated therapeutic potency and outcomes . Thus, optimized delivery regimes and well-defined release kinetics appear to be logical prerequisites for safe and efficacious clinical application of biomolecules. For considering the application of Tβ4 in clinical trials, target cells of exogenous Tβ4 should be restricted to cells in the periodontal tissue.
What to know about hormonal imbalances While it is natural to experience hormonal imbalances at certain times in life, such as puberty, menopause, and pregnancy, some hormonal changes are related to underlying medical conditions. This article looks at the causes and symptoms of hormonal imbalances in men and women, as well as treatment and home remedies. Read now
Due to its molecular structure and low molecular weight, TB-500 is very versatile, mobile and possesses the ability to travel long distances through tissues. This means that when targeting injured areas (chronic or acute), TB-500 has the ability to circulate through the body and “find” those areas of injury in order to enhance the healing or growth process. Many users have also noted the added benefits of improved flexibility, reduced inflammation in tendons, re-growth of lost hair, and darkening of grayed hair.
Eventually I found Dr Kristaps Paddock, a naturopathic doctor and 5-HTP expert from Maryland in the US. He said one benefit 5-HTP has over SSRIs is that it kicks in quickly for those with anxiety and depression. "Serotonin has a short metabolic half-life, so it metabolises very, very fast. It goes into the body and out at a great speed, unlike SSRIs, which take a while to take effect so a sufferer wouldn't be feeling good during that time, and in fact may be feeling more suicidal. SSRIs also then have to be weaned off slowly, whereas you can stop taking 5-HTP instantly." Another bonus, of course, is that it's natural rather than synthetic. "If you're seriously considering the supplement, you have to weigh the positives and negatives against each other. The toxicity with 5-HTP is lower than that of SSRIs, since it's natural. Also because it's metabolised much quicker, it'd get out of your system more quickly if there were any problems. On the other hand, the research basis for 5-HTP is dramatically lower, so it's important to think of that."
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.
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.
I bought 200mg "double strength" tablets off Amazon. Immediately after taking them, I felt slightly better. After a week of taking one of these with my breakfast, I could easily get through a working day without being too panicked to concentrate on a screen. I still woke up with 'the fear' but it was lessened. Better yet, there seemed to be no notable side effects. I started recommending it to all my friends with mild depression or anxiety. I was in love.
Our research mainly focusses on this early social experiences that people have that can be positive or negative, and that can really shape our developing brain. There have been some very interesting studies, for example, with children that grew up in Romanian orphanages. And we know that that early start, where it's really deprived from social contact and physical contact, had a massive impact. So we see that oxytocin levels, for example, are much lower than we would expect in other kids.
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.
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.
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.
An interesting concept that has emerged from initial findings is that regeneration and fibrosis are competing events in the vertebrate heart. That is, if there is a capacity for injury-stimulated cardiomyocyte hyperplasia beyond a certain threshold, regenerative mechanisms will overcome scarring. Results consistent with this idea came from experiments with zebrafish possessing a ts mutation in the cell-cycle checkpoint kinase Mps1 (Poss et al., 2002b). As mentioned earlier, mps1 mutants were initially identified based on their defects in caudal fin regeneration. Serendipitously, mps1 mutants also showed defects in cardiac regeneration at a temperature restrictive for the mutation (Poss et al., 2002b). Instead of regenerating muscle in response to ventricular resection injury, mps1 mutants repaired wounds by forming large, collagen-rich scars. Inhibition of Fgf signaling also stunts cardiac regeneration and causes scarring (Lepilina et al., 2006). These results indicate that even vertebrates with high cardiac regenerative capacity have a default scarring mechanism; normally, regeneration somehow restricts this pathway (Fig. 8). The implication is exciting; perhaps by stimulating regeneration in a poorly-regenerative system like the mammalian heart, scarring events characteristic of myocardial infarction would be restricted by new muscle formation. Similarly, deterring cardiac scarring mechanisms would perhaps favor regeneration in mammals.
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.
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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).
In women, oxytocin is responsible for signaling contractions of the womb during labor. The hormone stimulates the uterine muscles to contract, so labor begins. It also increases the production of prostaglandins, which move labor along and increases the contractions even more. Because of this effect, synthetic oxytocin (pitocin) is sometimes used to induce a woman to start labor if she cannot start naturally, or it can be given to make contractions stronger if a woman's labor is slowing.
Silencing of the Tβ4 or Wnt5a gene was achieved by transfecting cells with small interfering RNA (siRNA). Cells were transfected with Tβ4 or Wnt5a siRNAs (30 nM) for 24 hours using Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA) according to the manufacturer's instructions. Cells were transfected with Silencer negative control siRNA using the same protocol.
RegeneRx is continuing with pre-clinical research, in collaborative arrangements with the National Institutes of Health, accumulating data on the effects of Tb4 and aiming for an IND application (Investigational New drug App-lication) to proceed with clinical studies. Phase I clinical trials will determine the ability of Tb4 to repair ulcers in diabetic patients and to reduce inflammation and accelerate recovery from burns and abrasions to the cornea.
The short half-life (<2h) of 5-HTP may inherently limit the therapeutic potential of 5-HTP, as the systemic 5-HTP exposure levels will fluctuate substantially, even with relatively frequent dosing. Such exposure fluctuations are usually associated with increased adverse event burden, resulting from Cmax drug spikes, and decreased clinical efficacy resulting from sub-therapeutic exposure for large parts of the day. It has been proposed that 5-HTP dosage forms achieving prolonged delivery would be more effective, as is generally the situation with short-acting active pharmaceutical ingredients.