[Experimental and clinical demonstration of the antiproliferative effect of a highly purified coal tar fraction in a special gel vehicle]. / Experimenteller und klinischer Nachweis der antiproliferativen Wirkung einer hochgereinigten Steinkohlenteer-Fraktion in einer speziellen Gelgrundlage.

In this study a combination of clinical and experimental investigations demonstrates the antiproliferative effect of the coal tar-containing preparation Berniter. From a concentration of 70 micrograms/ml onwards (= 0.35 micrograms coal tar/ml) Berniter inhibits DNA synthesis of transformed human keratinocytes in vitro. The growth inhibiting effect is reversible up to the ED50 concentration (257 micrograms Berniter/ml = 1.3 micrograms coal tar/ml). The tar-free vehicle has no identifiable effect on the proliferation of the cells at a concentration of 260 micrograms/ml. However, at higher concentrations (ED50 = 1023 micrograms/ml) the vehicle also inhibits cell growth, this inhibition being irreversible. The effect of Berniter and the tar-free vehicle on amino acid metabolism corresponds with the reduced growth rate. The ED50 concentrations (331 micrograms/ml for Berniter and 1445 micrograms/ml for the tar-free vehicle) are higher than those in the investigation of the proliferation. The clinical trial was performed in two groups of 12 and 11 patients, respectively, suffering from Psoriasis capillitii. After 3 days' topical treatment of both groups with salicylic acid for scaling, one group was treated for 4 weeks with betamethasone-17-valerate (in the following briefly called Bet-17-v), as a commercial lotion. The other group received Bet-17-v initially for 3 days and was then treated for 4 weeks with Berniter. The 4 parameters used for evaluation (erythema, scaling, infiltration and itching) showed a more significant improvement in the Berniter group than in the Bet-17-v group. Subjectively, treatment with Berniter was assessed to be preferable.(ABSTRACT TRUNCATED AT 250 WORDS)

[The possible nephrotoxicity of a bituminous coal dermatologic agent]. / Untersuchungen zur möglichen Nephrotoxizität eines steinkohlenteerhaltigen Dermatikums.

Nephrotoxic effects are discussed as a possible risk of dermatological coal tar preparations. Therefore, we have performed a renal tolerance study with a modern coal tar preparation for the scalp, Berniter. 15 healthy volunteers, randomly subjected to 3 different modes of application, applied the preparation: twice weekly (mode I) or daily (mode II) for a period of 8 weeks. In both modes, application time was 15 min. In mode III, the preparation was used under occlusion for 30 min every second day for a period of 4 weeks. Before, during and after treatment, renal functions and urinary phenol levels were assayed. No pathological change or impairment of renal functions was detected. A relationship between urinary phenol content and the coal tar treatment was not observed, either. We conclude that the coal tar preparation investigated here has no nephrotoxic properties.

In vitro comparison of antifungal effects of a coal tar gel and a ketoconazole gel on Malassezia furfur.

Malassezia furfur seems to be a major pathogenetic factor in seborrhoeic dermatitis, a frequent human skin disease. To estimate the antifungal properties of a coal tar gel (5 mg ml-1 coal tar) which is used in the treatment of seborrhoeic dermatitis of the scalp, we compared its effects on the in vitro growth of M. furfur with those of a ketoconazole gel (20 mg ml-1 ketoconazole). None of the gels was fungicidal within incubation times up to 20 min. During a single application, both gels remain on the skin for only 5 min. Fungicidal effects are consequently unlikely to play a substantial therapeutic role. Fungistatic effects were observed with both gels. In cultures inoculated with 1 x 10(3) cells ml-1, a 1:49 152 dilution of the ketoconazole gel and a 1:768 dilution of the coal tar gel still showed inhibitory effects. At inoculum densities of 1 x 10(5) ml-1, both gels were fungistatic only in dilutions of a maximum of 1:40. Our results suggest that under clinical treatment conditions the fungistatic activities of both preparations should be comparable.

[Inhibition of testosterone metabolism by 17-alpha-estradiol in rat liver slices]. / Hemmung des Testosteron-Stoffwechsels durch 17 alpha-Estradiol in Rattenleberschnitten.

Inhibition of the Testosterone Metabolism in Rat Liver Slices by 17 alpha-Estradiol. The influence of 17 alpha-estradiol (CAS 57-91-0), a hormonally almost inactive isomer of physiological 17 beta-estradiol, on the metabolism of [14C]-labeled testosterone in rat liver slices was investigated. The analysis of extracts from incubates (3.0 ml medium, 100 mg liver slices, 416 nmol [14C]-testosterone, 0.1-30 micrograms 17 alpha-estradiol, 37 degrees C, 30 min) by thin layer chromatography showed, that 30 micrograms of 17 alpha-estradiol inhibited the testosterone turnover in liver slices of female animals. The failure of a significant inhibitory effect in liver slices of male animals is attributed to the known, much smaller total turnover of testosterone in male liver cells. The amount of unchanged 4-en-3-oxo-steroid (testosterone and 4-androstene-3,17-dione) was increased by a factor of 2.65 and 2.25, respectively. With high probability, the inhibition was the result of a decreased hydrogenation of testosterone to dihydrotestosterone (DHT, 17 beta-hydroxy-5 alpha-androstan-3-one), catalyzed by 5 alpha-reductase, since the production rates of DHT and the DHT-transformation metabolites (5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3,17-dione) were significantly lowered (factors: 0.16, 0.61, 0.61, respectively). In further experiments 17 beta-estradiol and 17 alpha-ethinylestradiol could be shown to inhibit the testosterone turnover in liver slices of female rats, too, but to a lower extent that 17 alpha-estradiol (relative inhibitory effects: 17 alpha-estradiol:17 beta-estradiol:17 alpha-ethinylestradiol = 100 : 73 : 58).(ABSTRACT TRUNCATED AT 250 WORDS)

[Antiproliferative activity of a highly purified coal tar preparation in comparison with clobetasol-17-propionate]. / Antiproliferative Aktivität einer hochgereinigten Steinkohlenteer-Präparation im Vergleich mit Clobetasol-17-Propionat.

Coal tar and glucocorticosteroids are among the preparations used for the treatment of hyperproliferative inflammatory dermatosis. Coal tar generally seems to have a better effect on psoriasis capillitii than betamethasone-17-valerate. This finding is confirmed by investigations with human skin fibroblasts. The coal tar preparation Berniter has a strongly inhibitory effect on cell proliferation. The action of the preparation with tar can be clearly distinguished from the effect of the vehicle. At the ED50 concentration of the substance with tar, the vehicle without tar causes no inhibition. Based on weight equivalents Berniter has a greater inhibitory effect on proliferation of human skin fibroblasts than clobetasol-17-propionate. In the case of both substances protein biosynthesis is only affected at concentrations higher than those needed for the inhibition of proliferation. Berniter and the vehicle without tar have an equally strong effect on protein synthesis. Berniter affects the nucleoside triphosphatase bound to the nuclear membrane, and thus influences the nucleocytoplasmic transport of mRNA. The effect of the vehicle and the preparation containing tar on this parameter are very similar. Berniter has a positive effect on cell mobility. In preconfluent cultures the mobility of the cell is slightly increased and in confluent cultures significantly. Our results show that Berniter inhibits proliferation in cell cultures of human skin fibroblasts to a higher degree than clobetasol-17-propionate. It is to be assumed that neither the inhibition of protein synthesis nor the inhibition of mRNA transport play a causal role in the antiproliferative effect of coal tar. Inhibition of proliferation as a result of general damage to the cell can also be practically ruled out.