Photobiomodulation-based (LLLT) therapies show tantalizing promise for treatment of skin diseases. Confidence in this approach is blighted however by lamentable inconsistency in published experimental designs, and so complicates interpretation. Here we interrogate the appropriateness of a range of previously-reported treatment parameters, including light wavelength, irradiance and radiant exposure, as well as cell culture conditions (e.g., serum concentration, cell confluency, medium refreshment, direct/indirect treatment, oxygen concentration, etc.), in primary cultures of normal human dermal fibroblasts exposed to visible and near infra-red (NIR) light. Apart from irradiance, all study parameters impacted significantly on fibroblast metabolic activity. Moreover, when cells were grown at atmospheric O2 levels (i.e. 20%) short wavelength light inhibited cell metabolism, while negligible effects were seen with long visible and NIR wavelength. By contrast, NIR stimulated cells when exposed to dermal tissue oxygen levels (approx. 2%). The impact of culture conditions was further seen when inhibitory effects of short wavelength light were reduced with increasing serum concentration and cell confluency. We conclude that a significant source of problematic interpretations in photobiomodulation reports derives from poor optimization of study design. Further development of this field using in vitro/ex vivo models should embrace significant standardization of study design, ideally within a design-of-experiment setting.
Ovarian hyperstimulation syndrome (OHSS) incidentally occurs in controlled ovarian stimulation protocols and is associated with human chorionic gonadotropin (hCG) administration. OHSS is caused by increased vascular permeability (VP) and thought to be mediated by hypersecretion of vascular endothelial growth factor (VEGF) by granulosa cells. Low molecular weight (LMW)-LH agonists have a similar mode of action but a shorter half-life compared with hCG, which could potentially lead to a clinical benefit in reducing the risk for OHSS in controlled ovarian stimulation protocols. The objective of this study is to investigate the role of an orally active LMW-LH agonist in OHSS induction compared with recombinant LH (rec-LH) and hCG. Immature rats were hyperstimulated with pregnant mare serum gonadotropin, and ovulation was induced by hCG, rec-LH or a LMW-LH agonist. The degree of VP was determined by Evans Blue in the abdominal cavity. Ovaries were weighed, and VEGF concentration in the ovary was determined. Pregnant mare serum gonadotropin stimulation followed by single-dose hCG or rec-LH resulted in clear enlargement of the ovaries and increased VP and VEGF levels. However, ovulation induction with a single dose of the LMW-LH agonist did not result in increased VP and VEGF levels, and even multiple dosing to mimic a longer exposure did not induce OHSS symptoms. In conclusion, we demonstrated that the oral LMW-LH agonist did not induce VP in rat, indicative for OHSS, possibly due to reduced VEGF production. If this is translatable to human, this could potentially represent a clinical benefit in reducing the risk for OHSS when using these compounds in controlled ovarian stimulation protocols.
Objectives: Photoepilation is a commonly used technology in home-use devices (HUDs) and in professional systems to remove unwanted body hair using pulses of laser or intense pulsed light (IPL). Albeit HUDs and professional systems operate at different fluences and treatment regimes, both demonstrate high hair reduction. The underlying mechanisms, however, remain unknown partly due to high divergence of the existing literature data. The objective of this study was to develop an ex vivo photoepilation model with a set of criteria evaluating response to light pulses; and to investigate dose-response behavior of hair follicles (HFs) subjected to a range of fluences. Methods: After ex vivo treatment (single pulse, 810 nm, 1.7-26.4 J/cm 2 , 4-64 ms pulse) human anagen HFs were isolated and maintained in culture for 7-10 days. Response to light was evaluated based on gross-morphology and histological examination (H&E and TUNEL stainings). Results: HFs treated ex vivo demonstrated a dosedependent response to light with five distinct classes defined by macroscopic and microscopic criteria. Fluences below 13.2 J/cm 2 provoked catagen-like transition, higher fluences resulted in coagulation in HF compartments. Conclusion: Observed changes in the HF organ culture model were reflected by clinical efficacy. The developed photoepilation model provides an easy and fast method to predict clinical efficacy and permanency of light-based hair removal devices. Lasers Surg. Med.
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