Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present studies were conducted to identify factors in human purulent material that might limit or enhance the activity of ciprofloxacin against bacteria causing suppurative infection. Ciprofloxacin, imipenem, and ampicillin were tested with regard to binding or inactivation by pus. The bactericidal activity of ciprofloxacin and imipenem were tested against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, or Staphylococcus aureus in human pus with a pH of 6.0 incubated at 37 degrees C under aerobic or anaerobic conditions. The effect of single or combination drug therapy with 20 mg/kg of ciprofloxacin, imipenem, or rifampin given every 12 hours was tested against E. coli or P. aeruginosa in polymicrobic murine abscesses that had been produced by subcutaneous injection of either of those organisms mixed with Bacteroides fragilis and autoclaved human stool. Antibiotic levels and the number of bacteria surviving in pus were quantitated. Therapy of subcutaneous abscesses was delayed 72 hours to test drug efficacy against organisms in well-established infections. Levels of ampicillin, imipenem, or ciprofloxacin were reduced from 10 micrograms/ml to 3.1 +/- 4.0, 2.7 +/- 3, or 5.8 +/- 2 micrograms/ml, respectively, after incubation in eight pus specimens for 24 hours at 37 degrees C. Ampicillin levels were reduced to less than 1 microgram/ml in four pus specimens containing beta-lactamase. Imipenem levels were undetectable in two specimens and were 0.2 micrograms/ml in one specimen. Ciprofloxacin binding to pus supernate or sediment appeared to be explained by its binding to the deoxyribonucleic acid (DNA) present in pus. Activity of 5 micrograms/ml of ciprofloxacin against four E. coli or K. pneumoniae strains in pus in vitro was greater than that of twofold higher concentrations of imipenem. The bactericidal activity of ciprofloxacin and imipenem were comparable but substantially reduced against S. aureus and P. aeruginosa in pus. Ciprofloxacin alone or regimens combining ciprofloxacin with rifampin or rifampin plus imipenem reduced the number of E. coli in polymicrobic subcutaneous abscesses but had little effect on P. aeruginosa in polymicrobic abscesses. The anaerobic abscess milieu appeared to inhibit the growth of P. aeruginosa. Ciprofloxacin activity in abscess fluid did not appear to be adversely affected by acid pH, aerobic or anaerobic conditions of incubation, the abscess constituents, or the binding of ciprofloxacin to the DNA in pus. Ciprofloxacin was bound to DNA of bacterial or human origin. Binding by pus was reversible, and binding to DNA extracts of pus was blocked by pretreatment of extracts with deoxyribonuclease but not by pretreatment with ribonuclease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of the abscess environment on the antimicrobial activity of ciprofloxacin. 258 67

An early event in acute and chronic inflammation and associated diseases such as atherosclerosis and rheumatoid arthritis is the induced expression of specific adhesion molecules on the surface of endothelial cells (ECs), which subsequently bind leukocytes. Peroxisome proliferator-activated receptors (PPARs), members of the nuclear receptor superfamily of transcription factors, are activated by fatty acid metabolites, peroxisome proliferators, and thiazolidinediones and are now recognized as important mediators in the inflammatory response. Whether PPAR activators influence the inflammatory responses of ECs is unknown. We show that the PPAR activators 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), Wyeth 14643, ciglitazone, and troglitazone, but not BRL 49653, partially inhibit the induced expression of vascular cell adhesion molecule-1 (VCAM-1), as measured by ELISA, and monocyte binding to human aortic endothelial cells (HAECs) activated by phorbol 12-myristate 13-acetate (PMA) or lipopolysaccharide. The "natural" PPAR activator 15d-PGJ(2) had the greatest potency and was the only tested molecule capable of partially inhibiting the induced expression of E-selectin and neutrophil-like HL60 cell binding to PMA-activated HAECs. Intracellular adhesion molecule-1 induction by PMA was unaffected by any of the molecules tested. Both PPAR-alpha and PPAR-gamma mRNAs were detected in HAECs by using reverse transcription-polymerase chain reaction and a ribonuclease protection assay; however, we have yet to determine which, if any, of the PPARs are mediating this process. These results suggest that certain PPAR activators may help limit chronic inflammation mediated by VCAM-1 and monocytes without affecting acute inflammation mediated by E-selectin and neutrophil binding.
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PMID:Peroxisome proliferator-activated receptor activators target human endothelial cells to inhibit leukocyte-endothelial cell interaction. 1047 50