[Terbinafine-resistant dermatophytoses and onychomycosis due to Trichophyton rubrum]. / Terbinafin-resistente Dermatophytosen und Onychomykose durch Trichophyton rubrum.

BACKGROUND: In recent years, therapy-refractory courses of dermatophytoses have increasingly become the focus of attention. The most frequent pathogens are Trichophyton (T.) rubrum and T. mentagrophytes. In addition to local therapy, first-line treatment includes terbinafine, an allylamine antifungal agent that acts by inhibiting squalene epoxidase and thus interfering with ergosterol synthesis. In refractory cases, terbinafine resistance due to point mutation in the squalene epoxidase gene has been frequently detected. OBJECTIVES: The aim is to present specific aspects in the epidemiology of dermatophytoses with terbinafine resistance and to illustrate them on the basis of four patient cases including diagnostic procedures. MATERIALS AND METHODS: A review of handbook knowledge, a selective literature search, and a review of four patient cases were performed. RESULTS: Detection of the terbinafine resistance was performed by in vitro testing using the breakpoint method as well as sequencing of the Trichophyton isolate and detection of the point mutation with amino acid substitution at position L393F or F397L of squalene epoxidase. CONCLUSION: In refractory and recurrent dermatophytoses, terbinafine resistance should be considered, especially in T. mentagrophytes and T. rubrum, and in vitro resistance testing of the dermatophyte and point mutation analysis of squalene epoxidase (SQLE) should be performed. Therapeutically, intermittent administration of itraconazole in combination with antifungal local therapy is recommended. Nevertheless, a recurrent course is to be expected and long-term therapy with itraconazole is usually necessary.

Soy induces phase II enzymes but does not inhibit dimethylbenz[a]anthracene-induced carcinogenesis in female rats.

Isoflavones in soy may play a role in the prevention of cancer through their capacity to affect antioxidant or protective phase II enzyme activities. This study evaluated the effects of dietary isoflavone levels on the induction of antioxidant and phase II enzyme activities and inhibition of breast carcinogenesis. Female Sprague-Dawley rats (36 d) were fed one of four purified diets with casein, or with soy containing three levels of isoflavonoids (0.03, 0.4 or 0.81 mg/g diet; low, middle and high level of isoflavones, respectively). After 2 wk, enzyme activity was determined of rats (n = 6-7) from each diet group. Liver glutathione peroxidase and glutathione reductase activities, blood glutathione levels, kidney glutathione S-transferase and colon quinone reductase (QR) activities were greater in rats consuming the high isoflavone diet compared to rats consuming the casein diet. Kidney QR and liver, kidney, small intestine, and colon UDP-glucuronosyltransferase activities were greater in rats fed the high isoflavone diet compared to rats fed the casein and low-isoflavone diets. Liver and blood oxidized glutathione were lower in rats fed the high-isoflavone diet compared to those fed the low-isoflavone diet. A subset of rats (n = 86) was fed the purified diets for 2 wk and intubated with dimethylbenz[a]anthracene or peanut oil and palpated weekly for tumors. At 13 wk, there was an inverse relationship (R(2) = 0.911, P < 0.09) between tumor incidence and increasing isoflavone intake. These data support the mechanism of soy and soy isoflavones as antioxidant and phase II enzyme inducers, but not as tumor inhibitors.

Soy feeding induces phase II enzymes in rat tissues.

The ability of soy to induce phase II detoxification enzymes was evaluated in male Sprague-Dawley rats. Soybeans contain biologically active compounds that are known inducers of phase II enzyme activity. Rats were fed soy flour (SF) or soy protein isolate (SPI) to provide 75% of total protein as soy. Rats were given free access to food for one- and two-week periods before enzyme activity was compared with that of casein control groups (AIN-93G). Hepatic glutathione S-transferase (GST) activity was significantly greater in rats fed SF for one and two weeks and in rats fed SPI for two weeks than in controls. Quinone reductase activity was significantly greater (12- to 14-fold) in the colon of rats fed SF and SPI for two weeks and in serum (1.8- to 2-fold) in the SF group at one and two weeks. Liver, kidney, and small intestine uridine 5'-diphosphate-glucuronosyl transferase activity was significantly increased in the SPI and SF groups at two weeks. A time dependence in induction of phase II enzymes was observed in several tissues. There was no significant difference in total liver glutathione in either diet group compared with controls. The data indicate that dietary soy enhances phase II enzyme activity, especially quinone reductase and uridine 5'-diphosphate-glucuronosyl transferase, which could lead to protection from potentially harmful xenobiotics.