Peroxisome proliferator-activated receptor (PPAR) are nuclear hormone receptors that are activated by endogenous lipid metabolites. Previous studies have demonstrated that PPAR-alpha activation stimulates keratinocyte differentiation in vitro and in vivo, is anti-inflammatory, and improves barrier homeostasis. Recent studies have shown that PPAR-beta/delta activation induces keratinocyte differentiation in vitro. This study demonstrated that topical treatment of mice with a selective PPAR-beta/delta agonist (GW1514) in vivo had pro-differentiating effects, was anti-inflammatory, improved barrier homeostasis, and stimulated differentiation in a disease model of epidermal hyperproliferation [corrected]. In contrast to PPAR-alpha activation, PPAR-beta/deltain vivo did not display anti-proliferative or pro-apoptotic effects. The pro-differentiating effects persisted in mice lacking PPAR-alpha, but were decreased in mice deficient in retinoid X receptor-alpha, the major heterodimerization partner of PPAR. Furthermore, in vitro PPAR-beta/delta activation, aside from stimulating differentiation-related genes, additionally induced adipose differentiation-related protein (ADRP) and fasting induced adipose factor (FIAF) mRNA in cultures keratinocytes, which was paralleled by increased oil red O staining indicative of lipid accumulation, the bulk of which were triglycerides (TG). Comparison of differentially expressed genes between PPAR-beta/delta and PPAR-alpha activation revealed distinct profiles. Together, these studies indicate that PPAR-beta/delta activation stimulates keratinocyte differentiation, is anti-inflammatory, improves barrier homeostasis, and stimulates TG accumulation in keratinocytes.
Germline mutations in the fumarate hydratase gene (FH) predispose to multiple cutaneous and uterine leiomyoma syndrome (MCL) and MCL associated with renal cell cancer. MCL is inherited in an autosomal dominant pattern, manifesting as skin leiomyoma and uterine fibroids in affected individuals. Fumarate hydratase, a component of the tricarboxylic acid cycle, acts as a tumor suppressor gene in the development of cutaneous and uterine leiomyoma and renal cell cancer in this syndrome. Here we report the clinical and mutational analysis of five families with MCL, with the identification of five new mutations affecting highly conserved residues of the FH protein. These results provide further evidence for the role of the FH gene in the pathogenesis of MCL.
IMPORTANCE Potentially harmful chemicals are released when tissues are vaporized. Laser hair removal (LHR) causes heating and often vaporization of hairs, producing both a signature malodorous plume and visible particulates.OBJECTIVE To characterize the chemical composition and quantify the ultrafine particle content of the plume generated during LHR. DESIGN, SETTING, AND PARTICIPANTSIn the laser center of a large academic hospital, discarded terminal hairs from the trunk and extremities were collected from 2 adult volunteers. The hair samples were sealed in glass gas chromatography chambers and treated with a laser. The laser plume was analyzed by gas chromatography-mass spectrometry (GC-MS). During LHR treatment, two 6-L negative pressure canisters were used to capture 30 seconds of laser plume, and a portable condensation particle counter was used to measure ultrafine particulates (<1 μm). Ultrafine particle concentrations were measured within the treatment room, within the waiting room, and outside the building. MAIN OUTCOMES AND MEASURESThe chemical content of the laser plume was analyzed with GC-MS and screened for aerosolized toxins using Environmental Protection Agency-certified methods. The ambient concentration of ultrafine particles during LHR was measured by condensation particle counters.RESULTS Analysis with GC-MS identified 377 chemical compounds. Sixty-two of these compounds, of which 13 are known or suspected carcinogens and more than 20 are known environmental toxins, exhibited strong absorption peaks. During LHR, the portable condensation particle counters documented an 8-fold increase compared with the ambient room baseline level of ultrafine particle concentrations (ambient room baseline, 15 300 particles per cubic centimeter [ppc]; LHR with smoke evacuator, 129 376 ppc), even when a smoke evacuator was in close proximity (5.0 cm) to the procedure site. When the smoke evacuator was turned off for 30 seconds, there was a more than 26-fold increase in particulate count compared with ambient baseline levels (ambient baseline, 15 300 ppc; LHR without smoke evacuator for 30 seconds, 435 888 ppc). CONCLUSIONS AND RELEVANCEThese findings establish the concern that the burning-hair plume often present during LHR should be considered a biohazard, warranting the use of smoke evacuators, good ventilation, and respiratory protection, especially for health care workers with prolonged exposure to LHR plume.
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