8 results match your criteria: "Center of Drug Research and Medical Biotechnology[Affiliation]"

Background & Aims: The orphan nuclear receptor HNF4alpha is a member of the hepatic transcription factor network. This protein plays a pivotal role in liver development and hepatocellular differentiation. Nine splice variants have been identified, some of which are specifically regulated in disease.

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Oxidized low-density lipoprotein (oxLDL) is an important risk factor for vascular injury. Its role on coronary vasoconstriction remains speculative. Endothelial monooxygenases (cytochrome P450s [CYPs]) are regulators of vascular tonus through production of epoxy fatty acids.

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There is substantial evidence for a causal relationship between genetic variability of the CYP2D6 gene and changes in the pharmacokinetics of drugs. Therefore, knowledge of single-nucleotide polymorphisms (SNPs) prior to drug administration is highly desired for assisting in the development of individualized pharmacotherapy. We therefore developed a robust assay that detects common CYP2D6 alleles within 60 minutes of blood withdrawal and links carriers of the variant CYP2D6*3 and *4 alleles to the pharmacokinetics of tramadol.

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Testosterone, cytochrome P450, and cardiac hypertrophy.

FASEB J

October 2002

Center of Drug Research and Medical Biotechnology, Fraunhofer Institute of Toxicology and Aerosol Research, Hannover, Germany.

Cytochrome P450 mono-oxygenases (CYP) play an essential role in steroid metabolism, and there is speculation that sex hormones might influence cardiac mass and physiology. As CYP mono-oxygenases activity is frequently altered during disease, we tested our hypothesis that CYP mono-oxygenase expression and testosterone metabolism are altered in cardiac hypertrophy. We investigate major CYP mono-oxygenase isoforms and other steroid-metabolizing enzymes and the androgen receptor in normal, hypertrophic, and assist device-supported human hearts and in spontaneously hypertensive rats (SHR).

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Verapamil is a commonly prescribed cardiovascular drug, but surprisingly its metabolism in the target tissue of pharmacotherapy is basically unknown. We therefore investigated its biotransformation in human heart tissue and correlate the production of metabolites with the gene expression of major drug metabolising enzymes. Using electrospray LC-MS-MS and LC-MS3 experiments, a total of nine metabolites were observed in incubation experiments with verapamil and microsomes isolated from the human heart tissue, and this included a carbinolamine-, N-formyl-, ahemiacetale-, and formate-intermediate of N-demethyl- and O-demethylverapamil.

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Verapamil metabolism in distinct regions of the heart and in cultures of cardiomyocytes of adult rats.

Drug Metab Dispos

May 2001

Fraunhofer Institute of Toxicology and Aerosol Research, Center of Drug Research and Medical Biotechnology, Nicolai-Fuchs-Str. 1, D-30659 Hannover, Germany.

A substantial number of drugs act either directly or indirectly on the heart, but surprisingly, little is known about drug oxidation in the heart. We therefore investigated the metabolism of the calcium antagonist verapamil in microsomal fractions isolated from the left and right ventricle of heart muscle and in primary cultures of cardiomyocytes of adult rats. Metabolism of verapamil proceeded predominantly with microsomal fractions isolated from the right ventricle of rat heart, and in liquid chromatographic-tandem mass spectrometry (LC-MS/MS) and LC-MS(3) experiments four metabolites (M1-M4) could be identified.

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1. Primary cultures of cardiomyocytes provide a valuable tool for the study of the pharmacological and toxicological properties of drugs and chemicals, but for several technical reasons cardiomyocytes from adult animals are not routinely used in long-term culture. Because of significant advances in cardiovascular research, tissue engineering and cell transplantation, the need to isolate primary cells from adult animal and/or human tissue is likely to increase in the future.

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