As reactive oxygen species (ROS) have been implicated in the pathogenesis of periodontitis [24], we examined whether H2O2 could down-regulate or up-regulate Tβ4 expression in PDLCs. As shown in Fig 1A and 1B, Tβ4 mRNA and protein expressions were down-regulated by H2O2 in a time- and concentration-dependent manner. Because maximal Tβ4 mRNA and protein expressions were achieved with 200 μM H2O2 within 48 hours in PDLCs, this concentration was used in subsequent experiments.
The first time Ditzen and her colleagues did this experiment they found that for both men and women oxytocin improved communication and lowered cortisol, a stress hormone. But in a recent study published in Social Cognitive and Affective Neuroscience, Ditzen and her colleagues measured salivary alpha-amylase (sAA)—an enzyme tied specifically to social stress—and found that men and women responded differently. Women who got oxytocin showed a decrease in sAA whereas men showed an increase and reported feeling more intense emotions. Counterintuitively, these men were also better at communication during conflict: they smiled more, had more eye-contact and were more open about their feelings. These behaviors are essential for peaceful conflict resolution.
Serotonin syndrome (Serotonin toxicity) is caused by an excess of serotonin in the brain. It is most often caused by taking more than one Serotonin-enhancing substance at the same time, such as 5-HTP and an antidepressant medication. Symptoms range in severity according to the level of intoxication and may include increased heart rate, tremor, sweating, mental agitation, seizures, shock, organ failure and death (9).

5-HTP (5-Hydroxytryptophan) is a chemical by-product of the protein building block L-tryptophan. It is also produced commercially from the seeds of an African plant known as Griffonia simplicifolia 5-HTP is used for sleep disorders such as insomnia, depression, anxiety, migraine and tension-type headaches, fibromyalgia, obesity, premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), attention deficit-hyperactivity disorder (ADHD), seizure disorder, and Parkinson's disease..
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 cornea is the outer thin layer of epithelial cells protecting the eye. After wounding, timely resurfacing of the cornea with new cells is critical, to prevent loss of normal function and loss of vision. Corneal epithelial healing occurs in stages, with cells migrating, dividing and differentiating. Therapies for corneal injury are limited. Therefore, the recent finding that Tb4 promotes corneal wound repair in animal models offers hope for a therapeutic product that will improve the clinical outcome of patients with injured corneas.


5-HTP supplements are made using an extract from the seeds of Griffonia simplicifolia,a tree native to Africa (2). 5-HTP very rarely occurs naturally in what we eat, but tryptophan, from which 5-HTP is made in the body, is found in a variety of foods. The richest natural food sources include cheese, poultry, eggs, fish, nuts, soy, and various greens.
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.
Six hours later, the mice were returned to cages with the aggressive mice. The mice that were missing their oxytocin receptors didn't appear to remember the aggressive mice and show any fear. Conversely, when mice with increased numbers of oxytocin receptors were reintroduced to the aggressive mice, they showed an intense fear reaction and avoided the aggressive mice.
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There is also a positive feedback involved in the milk-ejection reflex. When a baby sucks at the breast of its mother, the stimulation leads to oxytocin secretion into the blood, which then causes milk to be let down into the breast. Oxytocin is also released into the brain to help stimulate further oxytocin secretion. These processes are self-limiting; production of the hormone is stopped after the baby is delivered or when the baby stops feeding.
When looking at studies that investigate carbohydrates per se, one study in overweight women given 8mg/kg 5-HTP for 5 weeks noted that while placebo did not reduce carbohydrate ingested (calories were reduced in placebo, but carbohdyrate remained at 38% of voluntary calorie intake) that 5-HTP also retained 38% of intake as carbohydrates despite consuming less calories and carbohydrates in total.[9] A decrease in both carbohydrate and dietary fat has been noted with 750mg 5-HTP daily for 2 weeks in diabetics (with no dietary guidelines given), but appeared to be reduced to a similar degree as calories overall.[10] Only one study supports these anecdotes, where the reduction in calories seemed to be acounted mostly for by carbohydrates (75% of observed reduction) and then fats (25%).[10]
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.

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One study investigating romantic stress that looked at nondepressed youth who went through a recent breakup and were given 60mg of Griffonica Simplicifonia (12.8mg 5-HTP) twice a day for 6 weeks in an open-label study noted reductions in percieved romantic stress when measured at the 3 week mark with no further improvement at 6 weeks; there was no control nor placebo group in this study.[29]
Melanotan II was originally developed as a treatment for sexual dysfunction. However, this was abandoned when the metabolite bremelanotide was developed instead for treatment of haemorrhagic shock. Melanotan II is usually injected subcutaneously for the purposes of sunless tanning, appetite suppression, inducing sexual desire and penile erection and other conditions such as rosacea and fibromyalgia. There are also dose forms available for nasal administration. The therapeutic dose is considered to be 0.01 mg/kg.

Jump up ^ Ballweber E, Hannappel E, Huff T, Stephan H, Haener M, Taschner N, Stoffler D, Aebi U, Mannherz HG (Jan 2002). "Polymerisation of chemically cross-linked actin:thymosin beta(4) complex to filamentous actin: alteration in helical parameters and visualisation of thymosin beta(4) binding on F-actin". Journal of Molecular Biology. 315 (4): 613–25. doi:10.1006/jmbi.2001.5281. PMID 11812134.
Indeed, the findings that progenitor cells of some form exist both in the regenerative zebrafish heart, and in the hearts of less-regenerative mammals supports this idea. Zebrafish have ostensibly found some method to optimize the activity of progenitor cells, perhaps either by maintaining more cells, or by harboring a more cultivating environment for regeneration. Also, both mammalian and nonmammalian hearts contain an epicardial cell layer, yet zebrafish have found some way to activate the epicardium after injury, a process linked with essential neovascularization of regenerating muscle (Lepilina et al., 2006. This result points to the adult mammalian epicardium as a potential cellular source to assist myocardial regeneration or survival. Indeed, mammalian myocardial infarcts typically show poor or insufficient neovascularization, a response that many are trying to improve experimentally. Recent findings have indicated that the G-actin sequestering protein, Thymosin-ß4, may influence the mammalian epicardium. Treatment of adult cardiac explants with Thymosin-ß4 induced the migration of fibroblasts, endothelial and smooth muscle cells as assessed by gene expression and cellular morphology (Smart et al., 2007). In addition, in vivo Thymosin-ß4 treatment could partially restore cardiac survival and function following coronary ligation (Bock-Marquette et al., 2004). Notably, Thymosin-ß4 expression is induced in the injured zebrafish heart, suggesting that fish naturally release this epicardial stimulant on injury (Lien et al., 2006).
People are using 5-HTP for absolutely everything from sleep disorders to OCD symptoms. After asking people in mental health Facebook groups whether they used it and why, I was inundated with responses. Sach Tennant, from London, takes it for her PMDD (premenstrual dysphoric disorder). "I only take it when I feel low and it only takes one hour to feel calm," she told me. "This month I only needed one to feel better. I don't get the zombie antidepressant feeling – you still have your emotions. Sleep is good on it. I used to have an inner voice that was male and used to bully me during PMT time. Noises seemed too loud, even like somebody eating a bag of crisps. Topping up with 5-HTP has stopped all this."
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.
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