(1/76) Topical psoriasis therapy.
Psoriasis is a common dermatosis, affecting from 1 to 3 percent of the population. Until recently, the mainstays of topical therapy have been corticosteroids, tars, anthralins and keratolytics. Recently, however, vitamin D analogs, a new anthralin preparation and topical retinoids have expanded physicians' therapeutic armamentarium. These new topical therapies offer increased hope and convenience to the large patient population with psoriasis. (+info)
(2/76) Gordonia alkanivorans sp. nov., isolated from tar-contaminated soil.
Twelve bacterial strains isolated from tar-contaminated soil were subjected to a polyphasic taxonomic study. The strains possessed meso-diaminopimelic acid as the diagnostic diamino acid of the peptidoglycan, MK-9(H2) as the predominant menaquinone, long-chain mycolic acids of the Gordonia-type, straight-chain saturated and monounsaturated fatty acids, and considerable amounts of tuberculostearic acid. The G + C content of the DNA was 68 mol%. Chemotaxonomic and physiological properties and 16S rDNA sequence comparison results indicated that these strains represent a new species of the genus Gordonia. Because of the ability of these strains to use alkanes as a carbon source, the name Gordonia alkanivorans is proposed. The type strain of Gordonia alkanivorans sp. nov. is strain HKI 0136T (= DSM 44369T). (+info)
(3/76) Systematic review of comparative efficacy and tolerability of calcipotriol in treating chronic plaque psoriasis.
OBJECTIVES: To evaluate the comparative efficacy and tolerability of topical calcipotriol in the treatment of mild to moderate chronic plaque psoriasis. DESIGN: Quantitative systematic review of randomised controlled trials. SUBJECTS: 6038 patients with plaque psoriasis reported in 37 trials. MAIN OUTCOME MEASURES: Mean difference in percentage change in scores on psoriasis area and severity index, and response rate ratios for both patients' and investigators' overall assessments of marked improvement or better. Adverse effects were estimated with the rate ratio, rate difference, and number needed to treat. RESULTS: Calcipotriol was at least as effective as potent topical corticosteroids, calcitriol, short contact dithranol, tacalcitol, coal tar, and combined coal tar 5%, allantoin 2%, and hydrocortisone 0.5%. Calcipotriol caused significantly more skin irritation than potent topical corticosteroids (number needed to treat to harm for irritation 10, 95% confidence interval 6 to 34). Calcipotriol monotherapy also caused more irritation than calcipotriol combined with a potent topical corticosteroid (6, 4 to 8). However, the number needed to treat for dithranol to produce lesional or perilesional irritation was 4 (3 to 5). On average, treating 23 patients with short contact dithranol led to one more patient dropping out of treatment owing to adverse effects than if they were treated with calcipotriol. CONCLUSIONS: Calcipotriol is an effective treatment for mild to moderate chronic plaque psoriasis, more so than calcitriol, tacalcitol, coal tar, and short contact dithranol. Only potent topical corticosteroids seem to have comparable efficacy at eight weeks. Although calcipotriol caused more skin irritation than topical corticosteroids this has to be balanced against the potential long term effects of corticosteroids. Skin irritation rarely led to withdrawal of calcipotriol treatment. Longer term comparative trials of calcipotriol versus dithranol and topical corticosteroids are needed to see whether these short term benefits are mirrored by long term outcomes such as duration of remission and improvement in quality of life. (+info)
(4/76) Bioavailability of the genotoxic components in coal tar contaminated soils in Fischer 344 rats.
The effect of chemical aging on the bioavailability and subsequent genotoxicity of coal tar (CT)-contaminated soils was evaluated in a 17-day feeding study using Fischer 344 male rats. Rats consumed a control diet or diets amended with soil, 0.35% CT, or soil freshly prepared or aged for 9 months with 0.35% CT. Mild treatment-related microscopic lesions in liver tissue and elevated enzyme levels in serum were detected in all CT treatment groups. The (32)P-postlabeling assay was employed to determine DNA adduct formation in treated animals. All CT treatment groups induced DNA adducts in both the liver and lung. Adduct levels were 3-fold higher in lung DNA compared to hepatic DNA. After correcting adduct levels for total ingested polycyclic aromatic hydrocarbons (PAHs), a significant decrease (p < 0.05) in adduct levels was observed in both CT/soil treatment groups compared to CT control in liver and lung DNA. Adduct profiles of (32)P-postlabeled hepatic and lung DNA displayed several nonpolar DNA adducts that comigrated with PAH-adducted calf thymus DNA standards as determined through both thin-layer chromatography (TLC) and high-pressure liquid chromatography (HPLC). These results suggest that soil, but not aging of contaminants in soil, decreases the bioavailability of genotoxic components in CT, as evidenced by DNA adduct analysis. (+info)
(5/76) DNA adduct measurements, cell proliferation and tumor mutation induction in relation to tumor formation in B6C3F1 mice fed coal tar or benzo[a]pyrene.
Coal tar is a complex mixture containing hundreds of compounds, at least 30 of which are polycyclic aromatic hydrocarbons, including the carcinogen benzo[a]pyrene (BaP). Although humans are exposed to complex mixtures on a daily basis, the synergistic or individual effects of components within a mixture on the carcinogenic process remain unclear. We have compared DNA adduct formation and cell proliferation in mice fed coal tar or BaP for 4 weeks with tumor formation in a 2 year chronic feeding study. Additionally, we have analyzed tumor DNA for mutations in the K-ras, H-ras and p53 genes. In the forestomach of mice fed either coal tar or BaP an adduct indicative of BaP was detected, with adduct levels increasing in a dose-responsive manner. K-ras mutations were detected in the forestomach tumors, with the incidence being similar in mice fed coal tar or BaP. These results suggest that the BaP within coal tar is associated with forestomach tumor induction in coal tar-fed mice. DNA adduct levels in the small intestine were not predictive of tumor incidence in this tissue; instead, the tumors appeared to result from compound-induced cell proliferation at high doses of coal tar. K-ras mutations were detected in lung tumors. Since lung tumors were not increased by BaP, coal tar components other than BaP appear to be responsible for the tumors induced in this tissue. H-ras mutations, primarily occurring at codon 61, were the most common mutation observed in liver tumors induced by coal tar. Since this mutation profile is observed in spontaneous hepatic tumors, components in the coal tar may be promoting the expansion of pre-existing lesions. (+info)
(6/76) Naphthalene and donor cell density influence field conjugation of naphthalene catabolism plasmids.
We examined transfer of naphthalene-catabolic genes from donor microorganisms native to a contaminated site to site-derived, rifampin-resistant recipient bacteria unable to grow on naphthalene. Horizontal gene transfer (HGT) was demonstrated in filter matings using groundwater microorganisms as donors. Two distinct but similar plasmid types, closely related to pDTG1, were retrieved. In laboratory-incubated sediment matings, the addition of naphthalene stimulated HGT. However, recipient bacteria deployed in recoverable vessels in the field site (in situ) did not retrieve plasmids from native donors. Only when plasmid-containing donor cells and naphthalene were added to the in situ mating experiments did HGT occur. (+info)
(7/76) 7H-benzo[c]fluorene: a major DNA adduct-forming component of coal tar.
Coal tar is a complex mixture that exhibits high carcinogenic potency in lungs of animals when administered in the diet. Studies have noted that lung tumor induction does not correlate with the benzo[a]pyrene content of coal tar, suggesting that other hydrocarbons may be involved in the observed tumorigenicity. Our previous studies have demonstrated that a major 'unknown' chemical-DNA adduct is formed in the lung of mice exposed to coal tar. We have used an in vitro rat microsomal activation system to generate the 'unknown' adduct with neat coal tar and fractions of coal tar obtained by chemical fractionation and HPLC. Chemical-DNA adduct formation was evaluated by (32)P-postlabeling using both multi-dimensional TLC and HPLC. GC-MS analysis of the coal tar fractions obtained from HPLC, which produced the 'unknown' adduct in vitro, demonstrated that the adducting hydrocarbon had a mass of 216. A careful evaluation of candidate hydrocarbons led to the conclusion that a benzofluorene derivative may be responsible for forming the 'unknown' chemical-DNA adduct. Comparative in vitro and in vivo studies on the adducting properties of all three isomers of benzofluorene indicated that 7H-benzo[c]fluorene is responsible for producing the 'unknown' adduct observed in the lung of mice ingesting coal tar. Animal feeding studies also demonstrated that 7H-benzo[c]fluorene formed considerably more lung DNA adducts than 11H-benzo[a]fluorene and 11H-benzo[b]fluorene. These data indicate that the four-ring polycyclic aromatic hydrocarbon 7H-benzo[c]fluorene, a hydrocarbon not previously shown to form DNA adducts in lung, is in fact a potent lung DNA adductor and is a candidate PAH for causing lung tumors in animals treated with coal tar. (+info)
(8/76) A novel skin penetration enhancer: evaluation by membrane diffusion and confocal microscopy.
PURPOSE: The aim of this study was to determine the in vitro transdermal efficacy of a Meyer Zall Laboratories (MZL) oil/water emulsion in two separate preparations containing the actives, coal tar and the non-steroidal anti-inflammatory drug, diclofenac sodium. METHOD: The release rate of the two active ingredients from MZL dermatological preparations, Exorex and Athru-Derm and four comparator products was determined using an enhancer cell system, whilst specific penetration characteristics of the MZL formulation were elucidated using confocal and electron microscopy. The latter properties were explored at both the organ level, using human skin, as well as at a cellular level using a melanoma cell line. RESULTS: While the in vitro release rates for all formulations was high, coal tar and diclofenac release from Exorex and Athru-Derm respectively was, at nearly all time intervals, significantly higher than from comparator products. Microscopy revealed the presence of spherical liposomal type structures in both the MZL lotion and a comparator gel. In the MZL lotion, the majority of these structures, referred to here as emzaloid particles, were in the order of magnitude of about 50 nm to 1 microm in diameter with a small minority exceeding these dimensions. After application of Athru-Derm to human skin, intact emzaloid particles of submicron dimensions were detected in the epidermis in association with the cell membranes. The affinity of the MZL lotion for cell membranes was further demonstrated with melanoma cells; in addition, the formulation was seen to penetrate even to the nucleus of viable cells. CONCLUSION: Overall the data suggest that the oil/water base in MZL formulations is a highly efficient transdermal vehicle able to transport a wide range of indication- specific actives to their site of action. (+info)