[Reduction by dithiocarbamate fungicide, zineb, of the activity of oxygenases of the rat liver microsomes: effects of 9% casein regimen].
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The effects of ultraviolet (UV) light on fungi and impression materials were tested. UV light (250 microW/cm2) killed most Candida organisms (10(3) cells/ml) within 5 minutes. UV light (8000 microW/cm2) killed most C. albicans (10(7) cells/ml) within 2 minutes of exposure. The effect of UV light on dimensional change and surface roughness of impression materials (irreversible hydrocolloid, agar, and silicone rubber) was tested. The results showed that neither dimensional change nor surface roughness of the impression materials were affected. The results of this study indicate that UV light disinfects impression materials that are contaminated with Candida organisms.
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The effect of benomyl administered orally (p.o.) and intraperitoneally (i.p.) on the activity of hepatic microsomal mixed-function oxidases (MFOs) was studied in rats. A dose of 100 mg/kg given i.p. reduced the activities of several hepatic drug-metabolizing enzymes 24 h following the treatment. A similar reduction in the activities of the MFOs was also noted 24 h following oral benomyl administration at a dose of 500 mg/kg. Furthermore, in vivo inhibition of drug metabolism by benomyl was demonstrated by increased pentobarbital sleeping-time 24 h after p.o. as well as i.p. dosing. No alterations were found in the serum sorbitol dehydrogenase (SDH) at 24 h after i.p. or oral benomyl indicating a lack of hepatotoxic effect. These results indicate that benomyl shows a route-independent effect on MFOs and is not toxic to the liver.
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Thiram has been reported to inhibit dopamine-beta-hydroxylase (D beta H), thereby affecting norepinephrine (NE) synthesis. Because NE is a neurotransmitter that is known to play an important role in the hypothalamic regulation of pituitary function, the acute effects of the thiram on the hormonal control of ovulation in the rat were investigated. Ovariectomized, estrogen-primed female rats were given a single injection of thiram (0, 6, 12, 25, 50, and 100 mg/kg, i.p.) at 1100 h and serum LH was measured in serial bleeds. Thiram at 100 and 50 mg/kg completely blocked the LH surge in all rats tested, while 12 and 25 mg/kg blocked the surge in 40 and 75% of the treated animals, respectively. Six mg/kg had no effect. Ovulation was then assessed in intact, proestrous females in response to thiram administration (0, 12, 25, or 50 mg/kg) at 0900, 1100, 1300, or 1800 h. Ovulation was blocked by 25 and 50 mg/kg at 1300 h in all rats, but when injected at 1100 h only the 50 mg/kg dose was effective. No such blockade was found with 50 mg/kg injected at 0900 and 1800 h. To assess the influence of thiram on the LH surge in intact rats, additional females were dosed at 1300 h on the day of proestrus and blood collected over that same day. Thiram at 50 mg/kg blocked the LH surge in all rats, while 25 mg/kg blocked the surge in 60% of the females tested. No effect occurred with 12 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)
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Syringomycin E is an antifungal cyclic lipodepsinonapeptide produced by Pseudomonas syringae pv. syringae. To understand the mechanism of action of syringomycin E, a novel resistant Saccharomyces cerevisiae strain, BW7, was isolated and characterized. Lipid analyses revealed that BW7 contained only the hydrophobic subspecies of sphingolipids that are normally minor components in wild type strains. This aberrant sphingolipid composition was the result of lack of alpha-hydroxylation of the amide-linked very long chain fatty acids, suggesting a defective sphingolipid alpha-hydroxylase encoded by the FAH1 gene. A yeast strain that lacks the FAH1 gene was resistant to syringomycin E, and failed to complement BW7. These results demonstrate that BW7 carries a mutation in the FAH1 gene, and that the lack of alpha-hydroxylated very long chain fatty acids in yeast sphingolipids confers resistance to syringomycin E.
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Human salivary histatins (Hsns) have been known to be potent antifungal agents against Candida albicans for more than a decade. Here, we report that Hsns are also effective in killing another medically important opportunistic fungal pathogen, Cryptococcus neoformans, which has become a new threat among the immunocompromised patients, especially AIDS patients. In fact, the cidal activity of Hsn-5 against C. neoformans is as high as that against C. albicans.
The echinocandin class of cyclic lipopeptides has been simplified to discover potent antifungal compounds. Namely A-192411 shows good in vitro activity against common pathogenic yeasts and has an acceptable safety window in vivo. Discovery, limited SAR, synthesis, biochemical and pharmaco-dynamic profiles of A-192411 are presented.