Mouse bone marrow macrophage (BMMs) of 5-week-old female ICR mice (Charles River Laboratories, Seoul, South Korea) were used as previously described [23]. Animals were maintained in accordance with the National Institute of Toxicological Research of the Korea Food and Drug Administration guideline for the humane care and use of laboratory animals Institutional Animal Care and Use Committee (IACUC) approval was obtained from Kyung Hee University (Seoul, Korea). Briefly, bone marrow of tibiae and femurs of mice were flushed with α-MEM. After removing erythrocytes with hypotonic buffer, cells were cultured in α-MEM containing 10% FBS for 24 h and adherent cells were discarded. Non-adherent bone marrow cells were transferred onto 100-mm non-coated petri dishes at 5×106 cells per dish and cultured in the presence of M-CSF (30 ng/ml) for 3 days. Condition medium (CM) was obtained from HPDLCs treated with 200 μM H2O2 or Tβ4 (0.5, 1 and 5 μg/mL) for 2 days. To evaluate the osteoclastogenic activity of CM from HPDLCs, we added the CM mixture (60% CM plus 40% fresh α-MEM without M-CSF or RANKL) or rh-Tβ4 to pre-osteoclast-stage cells and further cultured the cells for up to 5 days to achieve mature osteoclast differentiation BMMs (1.5 × 105 cells/well) and PDLCs (1.5 × 104 cells/well) were co-cultured for 7 days in the presence of M-CSF (30 ng/ml), RANKL (100 ng/mL), H2O2 (200 μM) or Tβ4 (0.5, 1 and 5 μg/mL) in α-MEM, supplemented with10% in 48-well plates under 5% CO2 atmosphere.
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).
Addiction vulnerability: Concentrations of endogenous oxytocin can impact the effects of various drugs and one's susceptibility to substance use disorders. Additionally, bilateral interactions with numerous systems, including the dopamine system, Hypothalamic–pituitary–adrenal axis and immune system, can impact development of dependence. The status of the endogenous oxytocin system might enhance or reduce susceptibility to addiction through its interaction with these systems. Individual differences in the endogenous oxytocin system based on genetic predisposition, gender and environmental influences, may therefore affect addiction vulnerability.[72] Oxytocin may be related to the place conditioning behaviors observed in habitual drug abusers.

The product 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.
The activity of the PAM enzyme system is dependent upon vitamin C (ascorbate), which is a necessary vitamin cofactor. By chance, sodium ascorbate by itself was found to stimulate the production of oxytocin from ovarian tissue over a range of concentrations in a dose-dependent manner.[23] Many of the same tissues (e.g. ovaries, testes, eyes, adrenals, placenta, thymus, pancreas) where PAM (and oxytocin by default) is found are also known to store higher concentrations of vitamin C.[24]

When combined with antidepressants of the MAOI or SSRI class, very high parenteral doses of 5-HTP can cause acute serotonin syndrome in rats.[23][24] 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.[25]
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