Cognitive impairment has repeatedly been described in bipolar disorders… Serotonin (5-hydroxytryptophan; 5-HT) is possibly involved in these cognitive processes, more particularly in executive functions, learning, memory, and attention. The aim of this study was to investigate serotonergic vulnerability and its relation to cognitive functioning in healthy first-degree relatives of [bipolar disorders] patients…
Although Tβ4 contains only 43 amino acids, it appears to have a wide range of regenerative activities and specific sites on the molecule have been shown to mediate these effects (Goldstein & Kleinman, 2015; Sosne, Qiu, Goldstein, & Wheater, 2010). Both chemically synthesized and recombinant forms have shown efficacy for dermal healing in preclinical models and in human patients (Ehrlich & Hazard, 2012; Kim & Kwon, 2014, 2015; Malinda et al., 1999; Philp, Badamchian, et al., 2003; Philp & Kleinman, 2010; Philp et al., 2006; Ti et al., 2015; Treadwell et al., 2012). A dimeric form has been found to accelerate the rate of dermal healing in an animal model more rapidly than that of the parent molecule (Xu et al., 2013). Tβ4 has also shown repair and regenerative activity in a number of other injury models, such as traumatic brain injury, spinal cord injury, stroke, a model of multiple sclerosis, ischemic limbs, and cardiac damage due to ischemia (Bock-Marquette, Saxena, White, Dimaio, & Srivastava, 2004; Cheng, Kuang, Zhang, Ju, & Wang, 2014; Dube, Bollini, Smart, & Riley, 2012; Morris, Chopp, Zhang, Lu, & Zhang, 2010; Morris et al., 2014; Philp & Kleinman, 2010; Postrach et al., 2014; Smart et al., 2007; Sopko et al., 2011; Ti et al., 2015, Wang et al., 2012; Wei, Kim, Li, Wu, & Gupta, 2014; Xiong, Mahmood, Meng, et al., 2011; Zhang, Zhang, Morris, et al., 2009; Zuo et al., 2013). The processes and pathways for Tβ4-mediated repair are similar in these various tissues and support the observed promotion of dermal healing.
To investigate the effect of Tβ4 peptide on H2O2-induced signaling cascades, the activation states of three mitogen-activated protein kinases (MAPKs; p38, c-Jun N-terminal kinase [JNK] and extracellular signal-related kinase [ERK]) as well as NF-κB p65 were examined in PDLCs. H2O2 treatment induced the phosphorylation of p38, ERK, and JNK MAPK(s) and the nuclear translocation of NF-κB p65 (Fig 5A). Treatment of cells with Tβ4 peptide blocked H2O2-induced nuclear translocation of NF-κB p65 and phosphorylation of ERK and JNK (Fig 5B).
Cells were pretreated with indicated concentrations of Tβ4 peptide for 2 hours and then incubated with 200 μM H2O2 for 48 hours (A-C). Protein expressions were assessed by Western blot analysis (A). The production of NO (B) and PGE2 (C) were measured by Griess reaction and ELISA, respectively. Data replicated the quantifications of NO and PGE2 with the standard deviation of at least three experiments (n = 4). The bar graph shows the fold increase in protein expression compared with control cells. * Statistically significant differences compared with the control, p<0.05. # Statistically significant difference compared with the H2O2—treated group.
TB-500 is a synthetic fraction of the protein thymosin beta-4, which is present in virtually all human and animal cells. The main purpose of this peptide is to promote healing. It also promotes creation of new blood and muscle cells. The healing effects of TB-500 have been observed in tendons, ligaments, muscle, skin, heart, and the eyes. Thymosin beta-4 is naturally produced in higher concentration where tissue has been damaged. This peptide is also a very potent anti-inflamatory agent.
Depression. Some clinical research shows that taking 5-HTP by mouth improve symptoms of depression in some people. Some clinical research shows that taking 5-HTP by mouth might be as beneficial as certain prescription antidepressant drugs for improving depression symptoms. In most studies, 150-800 mg daily of 5-HTP was taken. In some cases, higher doses have been used.
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.
Thymosin β4 has been tested in multicenter trials sponsored jointly by RegeneRx Biopharmaceuticals Inc (Rockville, MD, USA) and Sigma Tau (Pomezia, Italy) in the United States and Europe in patients with bed sores, ulcers caused by venostasis, and Epidermolysis bullosa simplex and was found to accelerate bed sore and stasis ulcer repair by one month. It has also been tested in patients with chronic neurotrophic corneal epithelial defects and found to promote repair.
For depression: Most commonly, 150-800 mg daily is taken for 2-6 weeks. These doses are sometimes divided up and administered as 50 mg to 100 mg three times a day. Sometimes the dose starts out low and steadily increases every 1-2 weeks until a target dose is reached. Less commonly, higher doses are used. In one study, the dose is steadily increased up to 3 grams per day.
Nature has been very clever in a way. Without oxytocin, you know, babies are what they really are - I probably shouldn't say this on TV - but noisy, smelly animals that don't actually do anything useful. And, um, that's what oxytocin does. It gives them a special salience, a special beauty and allows us to bond with these defenceless little animals.
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.