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Feng S.,Tianjin University of Traditional Chinese Medicine | He X.,Tianjin University of Traditional Chinese Medicine | He X.,Modern Medicine
Current Drug Metabolism | Year: 2013

Xenobiotics are converted by cytochrome P450 (CYP450) into highly reactive metabolites (RMs) that covalently bind to the catalytic site of the enzyme itself, subsequently causing mechanism-based inhibition. This phenomenon is one of the fates of RMs in the liver. Depending on their affinity to nucleophiles (high-electron density compounds), RMs also may act as hepatotoxic agents by binding to intracellular macromolecules. The present study summarized 29 mechanism-based inhibitors (drugs) with clinical hepatotoxicity. Eighteen of these drugs cause hepatotoxicity (7 through idiosyncratic drug-induced liver injury) via their RMs. The liver injury caused by remaining 11 drugs, namely, fluoxetine, verapamil, furan-containing compounds, and human immunodeficiency virus protease inhibitors, cannot be excluded via RMs because of limited data. A regular pattern for RM-induced hepatotoxicity is summarized: (a) formation of RM-protein adducts that trigger immune responses; (b) covalent binding of RMs to intracellular macromolecules (mitochondria is a commonly victim) may lead to reactive oxygen species (ROS) overproduction, respiratory chain dysfunction, cell stress, and so on; and (c) RM overproduction, which results in glutathione (GSH) depletion. The binding mechanism of RMs to CYP450s and the quantitative parameters (KI, Kinact, and Kinact/K I) of the mechanism-based inhibitors of CYP450s are weakly correlated with the occurrence of hepatotoxicity, while the induction of CYP450 expression (11/29 drugs) may contribute to hepatotoxicity via excessive ROS and RM generation. These results suggest that mechanism-based inhibition is an indicator of RM formation and may thus be used to identify drugs with RM-induced hepatotoxic potential (particularly idiosyncratic drug-induced liver injury). © 2013 Bentham Science Publishers. Source


The aim of this study was to investigate the prevalence of Malassezia species from the body skin and external ear canal of healthy horses. The samples were obtained by scraping the skin surface from the nose, groin and dorsum and swabbing from the external ear canal of 163 animals, and then incubated on sabouraud dextrose agar and modified Dixon agar. Malassezia species were isolated from 34.9% of horses. The percentages of Malassezia species were 64.3% for Arab, 35.7% for Persian, 35.4% for Thoroughbred and 27.1% for Turkmen breeds. The greatest abundance of Malassezia species was found in the external ear canal (47.7%, representing significant difference with other sites), followed by nose (26.3%), groin (15.8%) and dorsum (10.5%) (P < 0.05). A total of 57 strains from six Malassezia species were detected with a frequency rate as follows: M. pachydermatis (33.3%), M. globosa (26.3%), M. sympodialis (14.1%), M. restricta (10.5%), M. obtusa (8.8%) and M. furfur (7%). The most common age-group affected was 1-3 years (59.4%). This study confirmed that cutaneous Malassezia microbiota in healthy horses varies by body site and age but not by breed and gender, representing M. pachydermatis as the most prevalent species on horse skin. © 2016 Blackwell Verlag GmbH. Source


Shen H.,Modern Medicine
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials | Year: 2011

To established an HPLC-MS assay to determine aconitine, mesaconitine and hypaconitine simultaneously in rat plasma and be used to investigate the pharmacokinetics of the three alkaloids. Three groups of rats were orally administered respectively with three decoctions including decoction of Radix Aconiti Laterlis, blend decoction of Radix Aconiti Laterlis and Radix Glycyrrhizae which decocted separately, decoction of Radix Aconiti Laterlis and Radix Glycyrrhizae which decocted together,the dosage of Radix Aconiti Laterlis was 1.5 g/kg. The contents of aconitine, mesaconitine and hypaconitine in rat plasma were detected using a liquid Chromatography-electrospray ionization/tandem mass spectrometry method. Pharmacokinetic parameters were estimated using DAS 2.0. The pharmacokinetic parameters of the three compounds obtained showed that Cmax and AUC of aconitine, mesaconitine and hypaconitine were decreased. MRT, t1/2 were prolonged and there was no obviously change in Tmax when Radix Aconiti Lateralis was combined with Radix Glycyrrhizae. The effect of decoction which decocted together was more prominent than which decocted separately. There are obvious effects on pharmacokinetic of Aconitine, Mesaconitine and Hypaconitine in Rat Plasma when Radix Aconiti Laterlis is combined with Radix Glycyrrhizae. Source


Shokri H.,Modern Medicine
Journal de Mycologie Medicale | Year: 2014

Objective: To investigate the DNA fingerprinting of Candida zeylanoides (C.zeylanoides) strains and the correlation between genotyping and antifungal susceptibility of C.zeylanoides. Methods: Paper discs containing nystatin, ketoconazole, fluconazole, Zataria multiflora (Z.multiflora) and Pulicaria gnaphalodes (P.gnaphalodes) essential oils were used in the disc diffusion method to evaluate the in vitro activity of the antifungal agents by measuring the mean diameter of inhibition around the discs. Yeast isolates were characterized by randomly amplified polymorphic DNA (RAPD) analysis using two different primers. Results: The mean inhibition zones were calculated 36.1. ±. 2.2. mm for ketoconazole, 25.3. ±. 2.0. mm for nystatin and 14.9. ±. 1.4. mm for fluconazole. Z.multiflora essential oil revealed a 58.6. ±. 2.6. mm mean zone of inhibition while P.gnaphalodes showed a 36.7. ±. 1.8. mm zone of inhibition against all isolates tested. A total of 14 strains of C.zeylanoides were divided into three types, 1 was genotype A strain, 2 genotype B strains and 11 genotype C strains. Strain of genotype A was significantly more susceptible to ketoconazole and nystatin than fluconazole (P<. 0.05). Strains of genotype B were more susceptible to ketoconazole than other antifungal agents (P>. 0.05). Strains of genotype C were significantly more susceptible to ketoconazole than fluconazole and nystatin (P<. 0.05). There was a significant correlation between C.zeylanoides genotypes and antifungal susceptibility (P<. 0.05). Conclusion: We concluded that all C.zeylanoides genotypes were susceptible to nystatin and Z.multiflora essential oil. The correlation between antifungal susceptibility and C.zeylanoides genotype may be of potential therapeutic significance and larger studies are needed to prove this finding. © 2014 Elsevier Masson SAS. Source


Ning Y.N.,Modern Medicine
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban | Year: 2012

To explore the mechanism of polypeptide extract from scorpion venom (PESV) on promoting anti-tumor effects of cyclophosphamide (CTX). The Lewis lung tumor model was established by subcutaneously implanting Lewis lung cells into C57BL/6 mice. The tumor-bearing mice were randomly divided into 4 groups, i. e., the model group, the cyclophosphamide (CTX) group, the polypeptide extract from scorpion venom (PESV) group, and the combination group (CTX + PESV), 10 mice in each group. The tumor growth curve was recorded. Changes of vascular endothelial growth factor-A (VEGF-A) and transforming growth factor-beta1 (TGF-beta1) expressions in the tumor microenvironment were detected using reverse transcription PCR and immunohistochemical assay. Changes of dendritic cells (DCs) phenotype CD80 and CD86 expressions in the tumor tissue were detected using immunofluorescence chemical assay. After 21 successive days of treatment, the growth of Lewis lung cancer transplantation tumor in the combination group was obviously inhibited (P<0.05). Compared with the model group,the expressions of CD80 and CD86 in the PESV group was somewhat enhanced, while those in the CTX group was somewhat lowered. Compared with the CTX group, the fluorescent signal strength and expressions in the combination group somewhat increased. Compared with the model group, the expressions of TGF-beta1 and VEGF-A mRNA decreased in the PESV group and the CTX group (both P<0.05). Compared with the PESV group and the CTX group, the expressions of TGF-beta1 and VEGF-A in the combination group both decreased (both P<0.05). PESV could inhibit the expressions of VEGF and TGF-beta1, promote the maturation of DCs, recover its antigen uptake presentation function, and reverse the immune injury to the body by CTX, thus playing a role in inducing the tumor cell apoptosis. Source

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