Bromodeoxyuridine (BrdU), a thymidine analogue, can be incorporated into the DNA of dividing cells and is widely used to label new cells.61-63 To label proliferating cells, BrdU (100 mg/kg) was injected i.p. daily starting at day 1 post TBI for 10 days. The number of BrdU-positive cells found in the ipsilateral cortex, DG, and CA3 areas was significantly increased 35 days after TBI compared with sham controls.18,34,64,65 Tβ4 treatment further increased the number of BrdU-positive cells compared to saline controls.34 The increased number of BrdU-positive cells may result from effects of Tβ4 on either increasing cell proliferation or reducing cell death of newborn cells. Our recent data show Tβ4 increases oligodendrocyte precursor cell proliferation and differentiation in animal models of stroke25 and experimental autoimmune encephalomyelitis.27 Tβ4 may not directly affect cell proliferation but inhibit cell death, for example, in corneal and conjunctival epithelial cells treated with benzalkonium chloride in vitro66 and endothelial precursor cells under serum deprivation.67 Our data further show that neurogenesis increases in TBI rats treated with Tβ4, suggesting that Tβ4 promotes newborn cells to differentiate into neurons. This is consistent with the effect of Tβ4 on promoting epicardium-derived progenitor cell differentiation into endothelial and smooth muscle cells to form the coronary vasculature.22 Whether the increased number of BrdU-positive cells in the brain of TBI rats treated with Tβ4 is tissue specific remains unknown. Tβ4 may not directly affect cell proliferation. Increased cell proliferation and neurogenesis are also possibly secondary to that Tβ4-mediated angiogenesis, as described later.
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).
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.
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.
It should be noted that supplemental 5-HTP can cause an increase in urinary 5-HIAA, which is the major metabolite of serotonin that is excreted in the urine. Increased urinary 5-HIAA is also sometimes a diagonistic marker for carcinoid tumors due to increased conversion of tryptophan to serotonin in these tumors, and in this case serum chromogranin A should be measured (as supplemental 5-HTP does not appear to increase chromogranin A).
5-HTP increases a brain chemical called serotonin. Some medications for depression also increase serotonin. Taking 5-HTP along with these medications for depression might increase serotonin too much and cause serious side effects including heart problems, shivering, and anxiety. Do not take 5-HTP if you are taking medications for depression.
Some of these medications for depression include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), amitriptyline (Elavil), clomipramine (Anafranil), imipramine (Tofranil), and others.
Thymosin Beta 4 is a peptide that was first found within the thymus gland. Since its discovery, other types of thymosin have been found in different tissues throughout test subjects. Thymosin Beta 4 is typically found in both types of muscles – skeletal (the muscles that are required to move) and smooth muscles (such as the heart). When damage occurs in a tissue, Thymosin Beta 4 is upregulated. Then when traumas take place, Thymosin Beta 4 is released in order to help the subject heal from the trauma. This peptide also helps to prevent adhesions from forming, which means there will be less scar tissue and potentially more flexibility. It has potent anti-inflammatory characteristics.
In a study that hasn’t been published yet, Feldman found that oxytocin receptor genes are also linked to empathy in couples. She looked at variants in the gene that have been linked with an increased risk for autism, a disorder that is marked by major social communication deficits. She found that the more of these “risk variants” a person had, the less empathy they showed toward their partner when that partner shared a distressing experience.
Oxytocin is known to be metabolized by the oxytocinase, leucyl/cystinyl aminopeptidase. Other oxytocinases are also known to exist. Amastatin, bestatin (ubenimex), leupeptin, and puromycin have been found to inhibit the enzymatic degradation of oxytocin, though they also inhibit the degradation of various other peptides, such as vasopressin, met-enkephalin, and dynorphin A.
However, as I’ve said elsewhere, depression is kind of like a check engine light on car, it’s a quiet ambiguous sign that something is not working somewhere in your neurobiology. There is literally dozens (perhaps hundreds) of different ways to attempt to treat depression. Amongst the vast number of options for treating depression, there is a couple of low hanging fruits; things you would want to start with before moving onto more radical options, like…
I was just diagnosed with achilles tendonosis in both of my achilles. I am an avid lifter as well as city leagues for football and basketball, I live in Montana so I hike a lot and participate In obstacle course races. My achilles have ground me to a halt over the last 3 months months. I have been referred to a surgeon for a Tenex procedure on both achilles. I am only 32 the last thing I want is have both of my achilles cut into. I’m looking at the TB-500 and BPC-157 to hopefully avoid surgery. I have done my research but am getting conflicting numbers as far as dosing. I am roughly 240 pounds and 6’5 could u recommend a dosage and cycle? Also I was wondering where the most effective injection site would be? Do I need it directly into the achilles itself or is local good enough?
It was also shown recently that delivery of Fgfs by release from peptide nanofibers, a gradual local delivery system, can increase neovascularization and reduce in-farct size in the ischemic rodent heart (Engel et al., 2006). Related to this, zebrafish have a natural ability to synthesize Fgfs after myocardial injury, a signal that appears to recruit Fgf receptor-expressing epicardial-derived cells toward regenerating muscle (Lepilina et al., 2006). Thus, what has been and what will be discovered about zebrafish heart regeneration is quite likely to illuminate possible strategies for enhancing regeneration in the mammalian heart (see Chapter 14.4).
“The study is kind of a high-water mark for the field, putting different levels all together: a robust behaviour, a brain region, and a cellular basis for it,” says Richard Tsien, a neuroscientist also at Langone. Tsien has been studying the action of oxytocin on neuronal circuits in detail, by examining slices of the hippocampus, a region involved in learning and memory. In a 2013 study6 of rats, Tsien's team found that oxytocin selectively acts on a type of cell called an inhibitory interneuron in a way that quiets background chatter within the neuronal circuit. “Oxytocin improved signal transmission, almost doubling the ability of information to flow through the system,” Tsien says. In effect, it is producing more signal and less noise.
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.
5-HTP has been investigated for its role in hot flashes as Selective Serotonin Reuptake Inhibitors (SSRIs) have been noted to reduce the occurrence of hot flashes and menopausal symptoms. In a study in menopausal females given 150mg 5-HTP daily (50mg taken thrice a day) for a period of one week failed to quantitivatively reduce the occurrance of hot flashes as assessed by a Flashmark Pro recording device.
In the experiments, an epithelial wound was made in the corneas of sedated rats. A Tb4 solution was applied at several concentrations to the injured eyes in one group of rats while another group was treated with a solution without Tb4. Following 12, 24 and 36 hours, the eyes were tested by microscopic observation for epithelial growth over the injured site. Investigators found the Tb4 accelerated corneal wound repair at doses of Tb4 similar to those found to repair skin wounds. When tested 24 hours after treatment, the rate of accelerated repair was proportional to the concentration of Tb4, with the highest dose (25 microgram) showing a threefold acceleration of epithelial cell migration, compared to untreated. Treatment with Tb4 showed anti-inflammatory effects, helping resolve the injury. An application to human cells in a model of human corneal cells in culture showed that Tb4 enhanced epithelial cell migration in vitro.