PubMed · 13188610
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S BOLLAG. About present internal therapy.. https://pubmed.ncbi.nlm.nih.gov/13188610/
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BACKGROUND: Treatment of common skin diseases such as psoriasis is complicated by differences between individuals in response to topical drug treatment and photochemotherapy. Individuality in hepatic expression of drug-metabolising enzymes is an important determinant of systemic drug handling; we investigated whether similar variation in cutaneous gene expression contributes to individuality in response to topical therapies. METHODS: We used quantitative real-time RT-PCR to demonstrate the expression in skin of a recently identified cytochrome P450, CYP2S1, in healthy volunteers (n=27) and patients with psoriasis (n=29). We also investigated regulation of CYP2S1 by ultraviolet radiation, psoralen-ultraviolet A (PUVA), and topical drugs used to treat psoriasis. FINDINGS: We found that CYP2S1 is expressed in skin and showed pronounced individuality in constitutive expression of the enzyme and its induction after ultraviolet irradiation or topical drug treatment. Cutaneous expression of CYP2S1 was induced by ultraviolet radiation, PUVA, coal tar, and all-trans retinoic acid; expression was significantly higher in lesional psoriatic skin than in adjacent non-lesional skin (geometric mean 3.38 [95% CI 2.64-4.34] times higher; p<0.0001), which implies that topical drugs are differentially metabolised in psoriatic plaque and non-lesional skin. We showed that all-trans retinoic acid is metabolised by CYP2S1, which has higher cutaneous expression than CYP26, previously described as the specific cutaneous P450 retinoic-acid-metabolising enzyme. INTERPRETATION: These findings increase our understanding of the interaction between therapeutic agents and the skin and suggest a functional role for CYP2S1 in the metabolism of topical drugs and in mediating the response to photochemotherapy in psoriasis.
In order to estimate the role of laminar flow of viscous, aromatic matter of carbonaceous precursor on microtextural preorientation in pregraphitization stage, we performed experiments with coal tar pitch (CTP). The principal hypothesis of preorientation of basic structural units (BSUs) in the case of laminar flow (pressure impregnation of CTP into porous matrix) and secondary release of volatiles during carbonization were studied. Glass microplates, planar porous medium with average distance between single microplates 5 microm were used as suitable porous matrix. Samples of CTP were carbonized up to 2500 degrees C. Optical microscopy reveals large flow domains in the sample of cokes carbonized between glass microplates. Raman microspectroscopy and high resolution transmission electron microscopy (HRTEM) show that at nanometric scale, the samples do not support the proposed hypotheses. With increasing temperature of pyrolysis, the graphitization of CTP impregnated into porous matrix proceeds to lower degree of structural ordering in comparison with single pyrolyzed CTP. This is explained by the release of volatile matter during carbonization in geometrically restricted spaces. More evident structural changes were discovered with the sample of single coke, where parts of fine grain mosaics, relicts of 'so called QI parts', reveal higher structural organization, in comparison with large and prolonged flow domains, similar to flow domains of cokes from microplates.
This case study describes occupational exposures to coal tar pitch volatiles (CTPV) as benzene soluble fraction (BSF), polycyclic aromatic hydrocarbons (PAHs) and total particulates at a unique operation involving the use of coal tar in the making of expansion joints in construction of a multi-level airport parking garage. A task-based exposure assessment approach was used. A set of 32 samples was collected and analyzed for total particulate and CTPV-BSF. Twenty samples of this set were analyzed for PAHs. Current American Conference of Governmental Industrial Hygienists (ACGIH(R)) respective threshold limit value-time weighted average (TLV-TWA) for insoluble particulates not otherwise specified (PNOS) is 10 mg/m(3) as inhalable dust, which roughly corresponds to 4 mg/m(3) total particulate; for CTPV as BSF the TLV is 0.2 mg/m(3), and for specific PAHs such as benzo(a)-pyrene (B[a]P), ACGIH suggests keeping exposure as low as practicable. The recommended Swedish exposure limit for B(a)P is 2 microg/m(3). The highest exposure levels measured were 12.8 mg/m(3) for total particulate, 1.9 mg/m(3) for coal tar pitch volatiles as BSF, and 12.8 microg/m(3) for B(a)P. Several of the CTPV-BSF results were over the TLV of 0.2 mg/m(3). The data set is limited; therefore, caution should be used in its interpretation.