Traumatic brain injury (TBI) remains a leading cause of mortality and morbidity worldwide. No effective pharmacological treatments are available for TBI because all Phase II/III TBI clinical trials have failed. This highlights a compelling need to develop effective treatments for TBI. Endogenous neurorestoration occurs in the brain after TBI, including angiogenesis, neurogenesis, synaptogenesis, oligodendrogenesis and axonal remodeling, which may be associated with spontaneous functional recovery after TBI. However, the endogenous neurorestoration following TBI is limited. Treatments amplifying these neurorestorative processes may promote functional recovery after TBI. Thymosin beta4 (Tβ4) is the major G-actin-sequestering molecule in eukaryotic cells. In addition, Tβ4 has other properties including anti-apoptosis and anti-inflammation, promotion of angiogenesis, wound healing, stem/progenitor cell differentiation, and cell migration and survival, which provide the scientific foundation for the corneal, dermal, and cardiac wound repair multicenter clinical trials. Here, we describe Tβ4 as a neuroprotective and neurorestorative candidate for treatment of TBI.
Total RNA was extracted from cells using Trizol (Invitrogen, Carlsbad, CA, USA) according to the manufacturer’s instructions. Reverse-transcription (RT)-PCR was performed using oligo deoxythymidine primer (Roche Diagnostics, Mannheim, Germany) in 20 μl volumes at 42°C for 60 min. The RT-PCR reaction was done with 1 μg of total RNA, 1 μl of 20 μM oligo dT primer, and 18 μl of reaction mixture by AccuPower RT/PCR PreMix (Bioneer, Daejeon, Korea). Then, PCR was performed in a 20 μl total mixture volume for 25 cycles at 95°C for 1 min, 55°C for 1 min, and 72°C for 1 min. Primer sequences are detailed in Table 1. PCR products were subjected to electrophoresis on 1.5% agarose gels and visualized with ethidium bromide.
It’s a compound that the body needs in order to make serotonin, which is our main “happiness hormone.” Per Dr. Oz, 5-HTP floods the brain with serotonin and helps minimize stress, sadness, anger, and anxiety. “5-HTP targets specific emotions that drive us to overeat,” Dr. Bhatia explains. And as she already mentioned, 5-HTP also reduces physical hunger pangs and emotional cravings. Ideally, the body makes its own 5-HTP from the amino acid tryptophan, found in foods like turkey and bananas. (Why not just eat more turkey or take a tryptophan supplement? If you struggle with mood or weight, it can be a sign that your body has trouble converting tryptophan to 5-HTP.) Besides making it yourself, the only other way to get 5-HTP is from a supplement. One we like is the BRI 5-HTP Supplement ($16 for 120 capules, Amazon).
Three groups of mice were individually placed in cages with aggressive mice and experienced social defeat, a stressful experience for them. One group was missing its oxytocin receptors, essentially the plug by which the hormone accesses brain cells. The lack of receptors means oxytocin couldn't enter the mice's brain cells. The second group had an increased number of receptors so their brain cells were flooded with the hormone. The third control group had a normal number of receptors.
Noteworthy: Many online sources sell an ineffective product. Also, peptides are fragile by nature and are not effective when they are taken orally (pills, shakes, etc) because they will be broken down by the digestive process. Instead, peptides are mixed with bacteriostatic water and then injected under the skin with an insulin needle. Peptide injections in this manner are nearly painless and have clinically proven effectiveness.
A: 5-HTP is classified as a dietary supplement. Because dietary supplements have not been thoroughly studied in the clinical setting, possible side effects and interactions with other drugs are not well-known. Also, because herbs and supplements are not strictly regulated by the U.S. Food and Drug Administration (FDA), these products are not required to be tested for effectiveness, purity, or safety. In general, dietary supplements should only be taken under the supervision of your health care provider. For more specific information, consult with your pharmacist about the potential for drug interactions based on your specific condition and current medications, particularly before taking any action. When your doctor prescribes a new medication, be sure to discuss all your prescription and over-the-counter drugs, including dietary supplements, vitamins, botanicals, minerals, and herbals, as well as the foods you eat. Always keep a current list of the drugs and supplements you take and review it with your health care providers and your pharmacist. If possible, use one pharmacy for all your prescription medications and over-the-counter products. This allows your pharmacist to keep a complete record of all your prescription drugs and to advise you about drug interactions and side effects. For more specific information, consult with your doctor or pharmacist for guidance based on your health status and current medications, particularly before taking any action. Jen Marsico, RPh
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 .
These proteins became of interest in neurobiology with the finding that in the nudibranch (sea slug) Hermissenda crassicornis, the protein Csp24 (conditioned stimulus pathway phosphoprotein-24), with 4 repeats, is involved in simple forms of learning: both one-trial enhancement of the excitability of sensory neurons in the conditioned stimulus pathway, and in multi-trial Pavlovian conditioning. The phosphorylation of Csp24, in common with post-translational modifications of a number of cytoskeleton-related proteins may contribute to actin-filament dynamics underlying structural remodeling of responsive cells.
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.
Plain sterile water is the most suitable diluent for TB-500. Alternatively it can be reconstituted with sterile saline (0.9% NaCl) or sterile bacteriostatic water (0.9% sodium chloride). Plain sterile water should be readily available to buy without prescription in any local pharmacy. Alternatively it can also be purchased online. It is even available on ebay.
Other supplements are available which have appetite supressant and mood enhancing effects similar to 5-HTP. These type of ingredients are often included, in optimal pre-formulated dosages in fat burners. Phenylethylamine is also another ingredient with mood enhancing potential that is often found in fat burners in place of 5-HTP. 5-HTP can be found in some sleep supplements, though in Australia they are replaced by ingredients such as GABA and phenibut.
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.