Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A qualitative and quantitative assessment was made of the development of hepatic drug-metabolizing enzymes (DME) in sheep as part of a study of the ability of the food-producing species to metabolize drugs. The following DME and components were measured in this study: cytochromes P-450 and b5 and NADPH and NADPH-dependent reductases associated with each of these cytochromes; cytochrome P-450-mediated reactions, including aniline and coumarin hydroxylases, aminopyrine N-demethylase, and 7-ethoxycoumarin 0-deethylase; a uridine diphosphoglucuronic acid glucuronyl transferase with 4-methylumbelliferone as substrate; and glutathione-S-transferase with dinitrochlorobenzene and dichloronitrobenzene as substrates. Amounts or activities of most of these components and enzymes increased up to and beyond the time of weaning. Amount of cytochrome b5 and uridine diphosphoglucuronic acid transferase activity were not affected by age, whereas NADPH cytochrome c (P-450) reductase activity actually decreased after weaning. In some instances (eg, coumarin hydroxylase, cytochrome P-450, and dinitrochlorobenzene-glutathione-S-transferase), differences from preweaning DME values were observed only after sheep were greater than or equal to 6 months old. All other DME activities were definitely increased, compared with the values in lambs before weaning (0 to 12 weeks old). Approximately a third of the sheep studied had some type of clinical disease that might have affected the DME activities. Diseases were classified as sore mouth, pneumonia, foot rot, parasitism, and systemic bacterial infections. Except in a few instances, these diseases had minimal effect on DME activities measured in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Maturational development of drug-metabolizing enzymes in sheep. 224 Jul 98

Children undergoing general anesthesia are at increased risk of severe aspiration pneumonitis. Cimetidine and ranitidine, specific histamine (H2-receptor) antagonists, when given 1-3 h preoperatively markedly reduce the acidity and volume of gastric content. A newer compound, famotidine, is a more specific antagonist with no inhibitory effect on the drug metabolizing microsomal enzyme systems of the liver (cytochrome P-450), in contrast to cimetidine. An additional clinical advantage is a possible longer duration of action. In order to evaluate these potential advantages we studied the effects of preanesthetic oral famotidine on gastric fluid pH and volume in 4 groups in a random manner. METHODS. With parental consent, 107 infants and children (ASA I status, 4 months to 14 years old, NPO for at least 6 h) received either no famotidine (n = 29) or 0.15 mg/kg (n = 27), 0.3 mg/kg (n = 25) or 0.6 mg/kg (n = 26) famotidine at 7.00 a.m. Following induction by mask with nitrous oxide/oxygen (N2O/O2) and enflurane (E) or i.v. thiopental, intubation was performed in all patients. Anesthesia was maintained with N2O/O2 and E. A orogastric double-lumen tube was passed into the stomach, and the gastric content was aspirated in a uniform manner. Gastric volume was recorded and pH values were measured with pH paper. RESULTS. In the control group, 28 of 29 patients (97%) had a pH less than 2.5, 18/29 (62%) had a gastric volume greater than 0.4 ml/kg and 17/29 (59%) had a pH less than 2.5 and gastric volume greater than 0.4 ml/kg, meaning an increased risk of pneumonitis if the child aspirates the gastric content. Famotidine administration was effective between 1.5 and 6 h after oral administration. Preoperative famotidine application produces pH values of gastric contents higher than 2.5 in all dosage groups (84%, 94%, 75%), and these differences were highly significant (P less than 0.001), whereas the gastric volume reduction with these doses was not significant. The incidence of pH less than 2.5 and volume of gastric contents exceeding 0.4 ml/kg did not vary with the different doses of famotidine. As there were no measurable differences in the effect of famotidine, we recommend that children at high risk of pulmonary aspiration receive 0.15 mg/kg famotidine orally at least 1.5 h but not later than 6 h before induction.
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PMID:[Famotidine dosage in children. The effect of different doses on the pH and volume of the gastric juice]. 228 7

The activity, pharmacokinetics, pharmacodynamics, efficacy, safety, drug interactions, and dosage and administration of moxifloxacin are reviewed. Moxifloxacin is an oral 8-methoxyquinolone antimicrobial approved in December 1999 for use in the treatment of acute bacterial sinusitis, acute bacterial exacerbations of chronic bronchitis, and community-acquired pneumonia. This fluoroquinolone is active against common community-acquired respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis), atypical pathogens, and many anaerobes. Moxifloxacin has an absolute bioavailability of 90% after oral administration and a mean elimination half-life of 12 hours. The drug is not a substrate or inhibitor of the hepatic cytochrome P-450 isoenzyme system thereby avoiding many potential drug interactions. Moxifloxacin has limited phototoxic potential. In clinical trials, moxifloxacin had clinical success rates of 88-97% and bacteriologic eradication rates of 90-97%. Reported adverse effects were primarily gastrointestinal (nausea, diarrhea) and were mild to moderate in severity. Moxifloxacin prolongs the QT interval by a mean + S.D. of 6 +/- 26 milliseconds above baseline and should be used with caution in patients with proarrhythmic conditions and avoided in patients receiving antiarrhythmia agents, such as quinidine, procainamide, amiodarone, and sotalol. The standard oral dosage is 400 mg once a day. Dosage adjustment is unnecessary in patients with renal dysfunction or mild to moderate hepatic dysfunction. Moxifloxacin is a safe and effective antimicrobial that will be useful for treating acute sinusitis, acute bacterial exacerbations of chronic bronchitis, and community-acquired pneumonia.
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PMID:Moxifloxacin: clinical efficacy and safety. 1125 73

We previously reported that the levels of epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) are depressed in microsomes prepared from lungs of rats with acute Pseudomonas pneumonia. We also showed a potential role for cytochrome P-450 (CYP) metabolites of arachidonic acid (AA) in contractile responses of both normal pulmonary arteries and pulmonary arteries from rats with pneumonia. The CYP2J subfamily enzymes (endogenous source of EETs and HETEs) are constitutively expressed in human and rat lungs where they are localized in vascular smooth muscle and endothelium. The purpose of this study was to determine if CYP2J proteins are modified in pneumonia. Pseudomonas organisms were injected via a tracheostomy in the lungs of rats. Later (44 h), lungs were frozen, and microsomes were prepared from pneumonia and control rat lung homogenates. Lung microsomal proteins were then immunoblotted with anti-CYP2B1/2B2, anti-CYP4A, anti-CYP2J9pep2 (which reacts with rat CYP2J3), anti-CYP2J6pep1 (which reacts with rat CYP2J4), anti-CYP2J2pep4, or anti-CYP2J2pep3 (both of which react with all known CYP2J isozymes). Western blotting revealed a prominent 55-kDa band with anti-CYP2J2pep3, anti-CYP2J2pep4, and anti-CYP2J6pep1 (but not anti-CYP2J9pep2) that was reduced in pneumonia compared with control lung microsomes. The CYP2B bands (51-52 kDa) were less prominent and not different between pneumonia and control lungs. CYP4A proteins (20-HETE sources) were not detected in rat lung microsomes. Therefore, rat lung contains a protein with immunological characteristics similar to CYP2J4, and this CYP is reduced after pneumonia. We speculate that CYP2J (but not CYP2B) enzymes and their AA metabolic products (EETs) are involved in the modulation of pulmonary vascular tone in pneumonia in rats.
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PMID:Pulmonary cytochrome P-450 2J4 is reduced in a rat model of acute Pseudomonas pneumonia. 1288 60