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)

We have previously demonstrated depressed vascular contractility in intralobar pulmonary artery (PA) rings isolated from rats with acute Pseudomonas pneumonia. Here we describe the role of arachidonic acid (AA) metabolites in the regulation of pulmonary vascular tone in inflammation. Pneumonia was induced by intratracheal injection of P. aeruginosa organisms. Rats were sacrificed 44 h later. EETs and 20-HETE were formed at significantly lower rates in pneumonia compared with control lung microsomes. Vasoactive effects of CYP metabolites (5,6-EET, 8,9-EET, 11,12-EET, 14,15-EET, and 20-HETE) on small PA rings from control or pneumonia rats were assessed in vitro. All four EETs and 20-HETE were more potent PA vasoconstrictors than KCl or phenylephrine (PE). However, this potency was attenuated in PA rings from pneumonia lungs compared with control. In contrast, pneumonia had no effect on COX activity [total pulmonary prostaglandin (PG), PGE(2), and 6-keto-PGF(1 alpha)]. In vitro vascular contractility to KCl, PE, or PGF(2 alpha) was assessed in small PA rings from control and pneumonia rats in the presence and absence of the COX-2 inhibitor NS-398 (10 microM). NS-398 did not reverse the attenuated contractile responses to KCl, PE, or PGF(2 alpha) in pneumonia rats. Nitrite/nitrate levels, inducible nitric-oxide synthase and heme oxygenase activities were all significantly elevated in pneumonia lungs. In conclusion, vasodilator PGs produced by COX-2 do not contribute to the depressed PA contractility in this model of pneumonia. Depressed pulmonary production and vasoconstrictor effects of CYP metabolites of AA (possibly due to increased NO and/or carbon monoxide) indicate a potential role for these vasoactive metabolites in this model of acute pneumonia.
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PMID:Cytochrome P450 metabolites of arachidonic acid but not cyclooxygenase-2 metabolites contribute to the pulmonary vascular hyporeactivity in rats with acute Pseudomonas pneumonia. 1130 33

Ketolides are a new class of macrolides designed particularly to combat respiratory tract pathogens that have acquired resistance to macrolides. The ketolides are semi-synthetic derivatives of the 14-membered macrolide erythromycin A, and retain the erythromycin macrolactone ring structure as well as the D-desosamine sugar attached at position 5. The defining characteristic of the ketolides is the removal of the neutral sugar, L-cladinose from the 3 position of the ring and the subsequent oxidation of the 3-hydroxyl to a 3-keto functional group. The ketolides presently under development additionally contain an 11, 12 cyclic carbamate linkage in place of the two hydroxyl groups of erythromycin A and an arylalkyl or an arylallyl chain, imparting in vitro activity equal to or better than the newer macrolides. Telithromycin is the first member of this new class to be approved for clinical use, while ABT-773 is presently in phase III of development. Ketolides have a mechanism of action very similar to erythromycin A from which they have been derived. They potently inhibit protein synthesis by interacting close to the peptidyl transferase site of the bacterial 50S ribosomal subunit. Ketolides bind to ribosomes with higher affinity than macrolides. The ketolides exhibit good activity against Gram-positive aerobes and some Gram-negative aerobes, and have excellent activity against drug-resistant Streptococcus pneumoniae, including macrolide-resistant (mefA and ermB strains of S. pneumoniae). Ketolides such as telithromycin display excellent pharmacokinetics allowing once daily dose administration and extensive tissue distribution relative to serum. Evidence suggests the ketolides are primarily metabolised in the liver and that elimination is by a combination of biliary, hepatic and urinary excretion. Pharmacodynamically, ketolides display an element of concentration dependent killing unlike macrolides which are considered time dependent killers. Clinical trial data are only available for telithromycin and have focused on respiratory infections including community-acquired pneumonia, acute exacerbations of chronic bronchitis, sinusitis and streptococcal pharyngitis. Bacteriological and clinical cure rates have been similar to comparators. Limited data suggest very good eradication of macrolide-resistant and penicillin-resistant S. pneumoniae. As a class, the macrolides are well tolerated and can be used safely. Limited clinical trial data suggest that ketolides have similar safety profiles to the newer macrolides. Telithromycin interacts with the cytochrome P450 enzyme system (specifically CYP 3A4) in a reversible fashion and limited clinically significant drug interactions occur. In summary, clinical trials support the clinical efficacy of the ketolides in upper and lower respiratory tract infections caused by typical and atypical pathogens including strains resistant to penicillins and macrolides. Considerations such as local epidemiology, patterns of resistance and ketolide adverse effects, drug interactions and cost relative to existing agents will define the role of these agents. The addition of the ketolides in the era of antibacterial resistance provides clinicians with more options in the treatment of respiratory infections.
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PMID:The ketolides: a critical review. 1214 46

Concentrations of serum clozapine, C-reactive protein (CRP) and alpha1 acid glycoprotein were greatly increased during a bacterial pneumonia in a 53-year-old woman. As the pneumonia subsided, and CRP and alpha1 acid glycoprotein normalised, serum clozapine concentration also decreased to the previous level. An increased serum clozapine and a lowered N-desmethylclozapine to clozapine ratio during the infection suggest a decreased cytochrome P(450) (CYP)1A2 activity. Cytokine-mediated CYP1A2 suppression is discussed.
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PMID:Bacterial pneumonia can increase serum concentration of clozapine. 1762 21

Recently, we demonstrated that pulmonary CYP2J4 content, a prominent source of EETs and HETEs formation in rat lungs, is reduced in pneumonia. Therefore, the purpose of this study was to determine the role of iNOS-derived NO in reduced pulmonary CYP2J4 protein content and decreased CYP metabolites in pneumonia. Rats were randomized to control, control plus 1400W (iNOS inhibitor), pneumonia, and pneumonia plus 1400W groups. Pseudomonas organisms were injected into lungs of pneumonia rats. At 40 h after surgery, rats were treated with either saline or 1400W for 4 h before death. Venous plasma samples were obtained for measuring nitrites/nitrates (NOx). There was no significant effect of 1400W on blood pressure measured in control or pneumonia rats, whereas 1400W reduced the elevated plasma NOx levels in pneumonia rats by half. CYP primary metabolites of AA formed at significantly lower rates in pulmonary microsomes from pneumonia rats compared with control rats. Treatment of pneumonia rats with 1400W resulted in a significant increase in the rate of formation of pulmonary EETs and omega-terminal HETEs compared with untreated pneumonia rats. The reduction in CYP2J4 protein content in pneumonia lung microsomes was also partially prevented by 1400W. Therefore, excess NO from iNOS decreases the pulmonary production of EETs and omega-HETEs in acute pneumonia. Inhibition of iNOS restores CYP2J4 protein content and CYP activity in acute pneumonia, indicating an important NO-CYP interaction in pulmonary responses to infection. We speculate CYP2J4 and its AA metabolites are involved in the modulation of pulmonary function in health and disease.
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PMID:Excess nitric oxide decreases cytochrome P-450 2J4 content and P-450-dependent arachidonic acid metabolism in lungs of rats with acute pneumonia. 1476 66