Native aortic valve vegetative endocarditis with Cunninghamella.
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Cunninghamella bertholletiae is a rare Mucor species that is seldom the cause for endocarditis of prosthetic heart valves. It is even a more uncommon cause of endocarditis of native heart valves. We present a case of Cunninghamella endocarditis of a native aortic valve in an immuno-compromised patient, diagnosed from tissue culture obtained at the time of surgery. There have only been two other reported cases of native valve endocarditis with a Mucor species, and in those cases, the diagnoses were made post-mortem. (+info)
Transformation of verapamil by Cunninghamella blakesleeana.
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A filamentous fungus, Cunninghamella blakesleeana AS 3.153, was used as a microbial model of mammalian metabolism to transform verapamil, a calcium channel antagonist. The metabolites of verapamil were separated and assayed by the liquid chromatography-ion trap mass spectrometry method. After 96 h of incubation, nearly 93% of the original drug was metabolized to 23 metabolites. Five major metabolites were isolated by semipreparative high-performance liquid chromatography and were identified by proton nuclear magnetic resonance and electrospray mass spectrometry. Other metabolites were characterized according to their chromatographic behavior and mass spectral data. The major metabolic pathways of verapamil transformation by the fungus were N dealkylation, O demethylation, and sulfate conjugation. The phase I metabolites of verapamil (introduction of a functional group) by C. blakesleeana paralleled those in mammals; therefore, C. blakesleeana could be a useful tool for generating the mammalian phase I metabolites of verapamil. (+info)
Effect of media composition and in vitro activity of posaconazole, caspofungin and voriconazole against zygomycetes.
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OBJECTIVES: The effect of different media and composition on the in vitro activity of posaconazole, caspofungin and voriconazole against 59 zygomycetes species was determined. METHODS: The media tested were RPMI 1640 medium with and without 2% glucose, antibiotic medium 3 (AM3) with and without 2% glucose, and high resolution (HR) medium. RESULTS: Posaconazole was significantly more active than caspofungin and voriconazole, both in RPMI 1640 medium with 2% glucose and in HR medium. Adding glucose improved the determination of end points, but had only minor influence on the MICs. MICs evaluated in AM3 were lower than in RPMI 1640 medium or HR medium. CONCLUSIONS: The in vivo effect of posaconazole in zygomycosis needs further evaluation. (+info)
Biotransformation of chrysin and apigenin by Cunninghamella elegans.
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Biotransformation of chrysin by Cunninghamella elegans NRRL 1392 produced apigenin, apigenin 7-sulfate, apigenin 7,4'-disulfate, and a new metabolite identified as chrysin 7-sulfate. On the other hand, fermentation of apigenin, using the same microorganism, yielded apigenin 7-sulfate and apigenin 7,4'-disulfate. The structures of the metabolites were established by spectral analysis, and acid and enzyme hydrolyses in addition to comparison with reference samples. (+info)
Phase II metabolites of etofesalamide in filamentous fungi.
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AIM: To study phase II metabolites of etofesalamide in filamentous fungi. METHODS: Seven fungi were screened to transform etofesalamide. The metabolites of etofesalamide were assayed using liquid chromatography coupled to mass spectrometry. The major metabolite was subject to enzymatic hydrolysis to confirm its structure. RESULTS: Etofesalamide was converted into two phase II metabolites: glucoside and riboside conjugates. Glucoside conjugate was the major product with a yield greater than 90%; no phase I metabolites were detected. CONCLUSION: Glucoside and riboside conjugations of etofesalamide in filamentous fungi differ from the phase II metabolism of glucuronidation in mammals. (+info)
Microbial transformation of mestranol by Cunninghamella elegans.
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The microbial transformation of an oral contraceptive, mestranol (1) by Cunninghamella elegans yielded two hydroxylated metabolites, 6beta-hydroxymestranol (2) and 6beta,12beta-dihydroxymestranol (3). Metabolite 3 was found to be a new compound. These metabolites were structurally characterized on the basis of spectroscopic techniques. (+info)
Structural elucidation of human oxidative metabolites of muraglitazar: use of microbial bioreactors in the biosynthesis of metabolite standards.
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Muraglitazar (Pargluva), a dual alpha/gamma peroxisome proliferator-activated receptor activator, is currently in clinical development for treatment of type 2 diabetes. This study describes the structural elucidation of the human oxidative metabolites of muraglitazar through the use of a combination of microbial bioreactors, NMR and accurate mass analyses, and organic synthesis. Plasma, urine, and feces were collected from six healthy subjects following oral administration of 14C-labeled muraglitazar (10 mg, 100 microCi) and pooled samples were analyzed. Approximately 96% of the recovered radioactive dose was found in the feces and 3.5% in the urine. The parent compound represented >85% of the radioactivity in plasma. The fecal radioactivity was distributed among 16 metabolites (M1-M12, M14-M16, and M8a) and the parent drug, of which hydroxylation and O-demethylation metabolites (M5, M10, M11, M14, and M15) represented the prominent human metabolites. The urinary radioactivity was distributed into several peaks including muraglitazar glucuronide (M13) and the parent drug. Low concentrations of metabolites in human samples prevented direct identification of metabolites beyond liquid chromatographic (LC)-mass spectrometric analysis. Microbial strains Cunninghamella elegans and Saccharopolyspora hirsuta produced muraglitazar metabolites that had the same high performance liquid chromatography retention times and the same tandem mass spectrometric (MS/MS) properties as the corresponding human metabolites. The microbial metabolites M9, M10, M11, M14, M15, and M16 were isolated and analyzed by NMR. Based on these LC-MS/MS and NMR analyses, and organic synthesis, the structures of 16 human oxidative metabolites were identified. The oxidative metabolism of muraglitazar was characterized by hydroxylation, O-demethylation, oxazolering opening, and O-demethylation/hydroxylation, as well as O-dealkylation and carboxylic acid formation. This study demonstrated the utility of microbial bioreactors for the identification of metabolites. (+info)
Peritonitis due to Cunninghamella bertholletiae in a patient undergoing continuous ambulatory peritoneal dialysis.
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Peritoneal dialysis-associated peritonitis due to fungi of the class Zygomycetes occurs very rarely. A case of fungal continuous ambulatory peritoneal dialysis peritonitis due to Cunninghamella bertholletiae is reported in a 39-year-old Aboriginal woman with end-stage renal failure and diabetes mellitus. This isolate was found to be resistant in vitro to amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole and voriconazole. However, this patient was successfully treated with voriconazole and removal of the Tenckhoff dialysis catheter. Zygomycoses are an emerging threat among immunocompromised patients, including those with chronic renal failure. Zygomycosis due to C. bertholletiae is frequently fatal and is often non-responsive to systemic antifungal therapy. This is believed to be the first reported case of C. bertholletiae causing peritonitis in humans and one of the minority of cases involving this organism with a successful outcome. (+info)