Pediococcus claussenii is a common brewery contaminant. We have sequenced the chromosome and plasmids of the type strain P. claussenii ATCC BAA-344. A ropy variant was chosen for sequencing to obtain genetic information related to growth in beer, as well as exopolysaccharide and possibly biofilm formation by this organism.
Herbal medicines can affect drug metabolizing enzymes. Therefore the effect of thymoquinone (TQ), the active ingredient of black seeds, was examined on rabbit liver drug metabolizing enzymes. Two groups of New Zealand female rabbits received TQ at 10 and 20 mg/kg/day orally and a control group of six animals each were killed after 8 weeks. Blood and livers were harvested and the activity of cytochrome P450 (CYP) and phase II enzymes in the microsomal and cytosolic preparations were measured by HPLC and ELISA methods. The liver enzymes ALT/AST and albumin were similar in the three groups. CYP1A2, CYP3A4, but not CYP2E1, were significantly diminished by TQ treatment. Of the phase II enzymes, glutathione-S-transferase (GST) and glutathione peroxidase (GPx) were significantly induced by the high TQ dose, while the total glutathione levels were unaffected. Glutathione reductase (GR), on the other hand, was significantly induced in the two experimental groups. Thymoquinone has differential effects on CYP and phase II enzymes. Inhibition of some CYP enzyme activities may lead to a hazardous herb-drug interaction. Induction of GR activity may explain the salutatory effect of the black seeds in inhibiting the generation of bioactive metabolites known to promote carcinogenesis and oxidative cell damage.
The objectives were to (1) investigate the effectiveness of hair cortisol concentration (HCC) as a measure of long-term stress in beef cattle and (2) determine whether meloxicam would decrease postcastration stress. Bull calves on two farms [site 1: Hereford cross (n = 73); site 2: Black Angus (n = 85)] were assigned to three treatments: (1) surgical castration with saline (CS, n = 52), (2) surgical castration with meloxicam (CM, n = 54), and (3) sham castration with saline (S, n = 52), balanced for age. Hair was collected from the left hip on day 0, prior to castration, and day 14, after 2 wk of regrowth from the day 0 location. Standing time was recorded on 129 calves (CS = 47, CM = 42, S, = 40) from 0 to 7 d post castration. On day 14, CS calves had 13.8% greater HCC than S (P = 0.031) and tended to be higher than CM calves (P = 0.095); CM and S calves did not differ. Standing time did not differ between treatments. Lower HCC in CM compared with CS calves indicates that meloxicam may be effective at reducing postcastration stress. With differences between treatments, HCC shows promise as a technique for measuring long-term stress in beef cattle.
Frequency of drug-drug interaction is high in most solid organ transplant recipients because of polypharmacy. These interactions involve, predominantly, the cytochrome P450 (CYP) enzymes. Several reviews described these interactions, but few focused on how these interactions are evaluated. This review summarizes current in vitro functional assays of CYP activity to assist in understanding the bidirectional relationship between immunosuppressants and CYP enzyme system. To achieve our goal we describe the constituents of CYP system followed by discussing their role in the common immunosuppressive drug-drug interactions. We also present the various in vitro assays used to evaluate modulation of CYP enzyme activity.
This study investigates the mechanism of cyclosporine A (CsA)-mediated nephrotoxicity by examining the hypothesis that CsA toxicity is mediated through its effect on the kidney drug metabolizing enzymes in a hyperlipemic rabbit model. Twenty-four female New Zealand white rabbits divided into four groups. Group 1 received regular diet. Group 2 received 1% cholesterol diet. Group 3 received CsA (25 mg/kg, orally once daily) and group 4 received 1% cholesterol diet and CsA (25 mg/kg, orally once daily). Cytochrome P450 2E1 (CYP2E1) activity in kidney microsomes was assessed by measuring p-nitrophenol hydroxylase activity. Generation of reactive oxygen species (ROS) was assessed by measuring malondialdehyde (MDA) and the protein carbonyl. Effect of CsA and hyperlipidemia on the antioxidant proteins were also assessed using standard techniques. CsA but not the high-cholesterol diet induced significant elevation in MDA, protein carbonyl and CYP2E1 activities in the kidney. The addition of cholesterol to CsA normalized ROS markers without affecting the CsA-enhanced CYP2E1 activity. Alone, CsA caused characteristic tubular injury, whereas the addition of high-cholesterol diet to CsA nearly abolished the tubular damage. CsA-enhanced rabbit kidney ROS and CYP2E1 activities. Hyperlipidemia attenuates CsA tubular injury, most probably due to normalization of renal ROS, but not CYP2E1 activity.
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