Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toenail tinea is a very recalcitrant dermatosis. Griseofulvin at > or = 500 mg/day is the current medication of choice, but it is minimally successful. In a controlled open trial ultramicrosize griseofulvin (UMSG) at doses of 660 and 990 mg/day was compared with itraconazole at 100 mg/day in 109 patients. At 4-week intervals, the patients were evaluated for their clinical and mycological statuses and adverse reactions. Treatment was given for up to 18 months. Compliance was checked by tablet counting. Response (cure, partial cure, marked improvement) was analyzed by the intent-to-treat method. Cured and partially cured patients were followed up. Except for one early dropout, the toenails (mean, 6 to 7) were involved. Cure or partial cure was found in 6% (UMSG at 660 mg), 14% (UMSG at 990 mg), and 19% (itraconazole at 100 mg) of patients (P = 0.2097); marked improvement was found in 36, 44, and 39% of patients in the three treatment groups, respectively. Most patients had to be treated for 18 months. Failure was related to short medication periods (adverse drug reactions, dropout). While stable cure was not obtained with UMSG at 660 mg, the higher dose of UMSG and itraconazole gave stable cures in the other patients. Side effects of nausea, diarrhea, and headache were found in 20, 26, and 11 patients, respectively (P = 0.0028), and the numbers in whom medication had to be discontinued differed, too (P = 0.0137). While there was no major difference with glutamic-pyruvic transaminase and gamma-GT, total and low-density lipoprotein cholesterol levels declined slightly in the itraconazole group (P = 0.0357 and P = 0.0639, respectively, at 3 months). More than 70% of the patients had an average compliance of > or = 90%; four patients (two dropouts) were poor compliers. In conclusion, it appears questionable whether griseofulvin can continue to be considered the "gold standard" in the treatment of toenail tinea. At present, itraconazole at 100 mg shows better efficacy and is better tolerated.
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PMID:Treatment of tinea unguium with medium and high doses of ultramicrosize griseofulvin compared with that with itraconazole. 825 24

Cortex Dictamni is a commonly-used traditional Chinese herbal medicine for the treatment of skin inflammation, tinea, and eczema. Recently, some studies reported that Cortex Dictamni might induce liver injury, suggesting more attention to its safety. The current study was designed to investigate subchronic toxicity of Cortex Dictamni aqueous extract (CDAE) and ethanol extract (CDEE) in mice and the potential hepatotoxicity mechanisms in vitro. Firstly, CDAE or CDEE groups were administrated with varying dosages (2.3, 4.6, or 9.2 g/kg/day, p.o.) in mice for 28 days in subchronic toxicity studies. General clinical signs and biochemical parameters were examined, and morphological analyses were conducted. Secondly, we identified the different constituents of CDAE and CDEE using HPLC-MS/MS and chose major components for further study. In order to determine the toxic components, we investigated the cytotoxicity of extracts and chosen components using CCK-8 assay in HepG2 cells. Furthermore, we explored the possible hepatotoxicity mechanisms of Cortex Dictamni using a high content analysis (HCA). The results showed that no significant differences of general clinical signs were observed in mice. Aspartate alanine aminotransferase (ALT) and aminotransferase (AST) were significantly increased in the high-dose CDAE and CDEE groups compared to the control group. Meanwhile, the absolute and relative liver weights and liver/brain ratio were significantly elevated, and histological examination of liver demonstrated cellular enlargement or nuclear shrinkage. In UPLC analysis, we compared the chemical constituents between CDAE and CDEE, and chose dictamnine, obakunone, and fraxinellone for hepatotoxicity evaluation in the in vitro studies. In the CCK-8 assay, CDAE, CDEE, dictamnine, obakunone, and fraxinellone decreased the cell viability in a dose-dependent manner after treatment for 48 h. Furthermore, the cell number decreased, while the nuclear intensity, cell membrane permeability, and concentration of reactive oxygen species were shown to increase, meanwhile, mitochondrial membrane potential was also changed in HepG2 cells following 48 h of compounds treatment using HCA. Our studies suggested that CDAE and CDEE have potential hepatotoxicity, and that the alcohol extraction process could increase toxicity. Dictamnine, obakunone, and fraxinellone may be the possible toxic components in Cortex Dictamni with dictamnine as the most potentially hepatotoxic component, whose potential hepatotoxicity mechanism may be associated with cell apoptosis. Moreover, this study could provide valuable data for clinical drug safety research of Cortex Dictamni and a good example for safety study of other Chinese herbal medicines.
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PMID:Subchronic Toxicity Studies of Cortex Dictamni Extracts in Mice and Its Potential Hepatotoxicity Mechanisms in Vitro. 3027 40