Severe sepsis is a common, expensive, and fatal condition with as many deaths annually as those from acute myocardial infarctions. The average cost per case seems to exceed $22,000. The increased morbidity and mortality attributed to sepsis could be due to the lack of our understanding of mediators and factors responsible for early cellular alterations and thus could not be intervened which res...

Symptom exacerbation due to stress is prevalent in many disease states, including functional disorders of the urinary bladder (e.g., overactive (OAB), interstitial cystitis/bladder pain syndrome (IC/BPS)); however, mechanisms underlying effects on micturition reflex function are unclear. In this study we designed and evaluated a stress-induced symptom (SISE) mouse model that demonstrates increa...

This is the first study performed in population from Bosnia & Herzegovina (BH), in which we analysed a significance of genetic variations in drug-metabolising enzyme, cytochrome P450 (CYP), in pathogenesis of Type 2 diabetes. We have determined allele frequencies for CYP2C9*2, CYP2C19*2, and CYP2D6*4 in diabetic patients and nondiabetic controls. Genomic DNA was extracted from blood samples col...

Both ritonavir and indinavir were readily metabolized by human intestinal microsomes. Comparison of the patterns of metabolites in incubations with enterocyte microsomes and expressed cytochrome P450 (CYP) isozymes and immunoinhibition and chemical inhibition studies showed the essential role of the CYP3A subfamily in the metabolism of both protease inhibitors by the small intestine. Ritonavir ...

Concomitant administration of grapefruit juice can increase the plasma concentration of numerous drugs in humans and decrease the concentration of a few others. Such elevations of drug plasma concentrations have, on occasion, resulted in adverse clinical effects. Increased concentrations are primarily mediated by chemicals in grapefruit juice, which inhibit the CYP 3A4 drug-metabolizing enzyme ...

The metabolism of vinorelbine, a new anticancer agent belonging to the vinca alkaloid family, was investigated in human liver microsomes. Vinorelbine biotransformation consisted of one saturable and one nonsaturable process, and the K(m) and V(max) values for the saturable process were 1.90 microM and 25.3 pmol/min/mg of protein, respectively. Several studies, including metabolism by cytochrome...

A unique cytochrome P450 (CYP) oxidoreductase (CPR) sustains activities of human microsomal CYPs. Its function requires toggling between a closed conformation enabling electron transfers from NADPH to FAD and then FMN cofactors open conformations forming complexes transferring electrons We previously demonstrated that distinct features the hinge region linking domain (FD) modulate conformer pos...

BACKGROUND Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA for treating cardiovascular disorders. The roles of cytochrome P450 enzymes (CYPs) in the metabolism of STS have remained unclear. This study aims to screen the main CYPs for metabolism of STS and study their interactions in vitro. METHODS Seven major CYPs were screened for metabolism of STS by hu...