Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.11.1.7 (peroxidase)
 65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study we have investigated the effect of six antibiotics (penicillin G, ceftazidime, cephotaxime, cephoperazon, ampicillin and piperacillin) on the neutrophil cytolytic activity by using a system constituted of phorbol-12-myristate-13-acetate-triggered neutrophils and 51Cr-labelled lymphoblastoid Daudi target cells. The results demonstrate that five of these drugs (ceftazidime, cephotaxime, cephoperazon, ampicillin and piperacillin) are capable of inhibiting the neutrophil cytolytic activity by inactivating the hypochlorous acid (HOCl) generated extracellularly by the myeloperoxidase pathway and crucial to the target cell lysis. Penicillin G had no effect on neutrophil-mediated cytolysis. Thus, these data demonstrate that ceftazidime, cephotaxime, cephoperazon, ampicillin and piperacillin lower the neutrophil-mediated target cell damage by a HOCl-scavenging mechanism, suggesting a possible cytoprotective role for these drugs during infections.
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PMID:Cytoprotection against neutrophil-delivered oxidant attack by antibiotics. 166 10

Nine clinical isolates of Haemophilus somnus were screened for their ability to use different transferrins as a source of iron growth. All nine strains were capable of using bovine but not porcine, human or chicken transferrin. A screening assay for siderophore production did not show any evidence of siderophore production by these strains. When iron-deficient cells from these strains were screened for their ability to bind peroxidase-conjugated transferrin, binding was detected with conjugated bovine, but not human or porcine transferrin. Competition binding studies demonstrated that the binding of peroxidase-conjugated bovine transferrin was competitively inhibited by unconjugated bovine transferrin but not transferrin from other species. The induction of receptor expression by low iron conditions was inhibited by chloramphenicol and rifampicin but not ampicillin indicating that new protein and mRNA synthesis was required for expression of receptor activity. Affinity isolation of receptor proteins with biotinylated bovine transferrin, but not human or porcine transferrin, yielded three proteins from H. somnus strain H74. Two of the proteins were identified as 105 kDa and 73 kDa iron-regulated outer membrane proteins. A third protein of 85 kDa that was isolated did not co-migrate with any iron-regulated outer membrane protein. Affinity isolation of receptor proteins from other strains of H. somnus yielded a 73 kDa protein from all strains and a 105 kDa and 85 kDa protein in four of the six strains analysed.
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PMID:Response of Haemophilus somnus to iron limitation: expression and identification of a bovine-specific transferrin receptor. 215 61

The effect of three antimicrobial agents, penicillin G, ampicillin, and chloramphenicol, on luminol-enhanced chemiluminescence of polymorphonuclear leukocytes stimulated by the chemoattractant formylmethionyl-leucyl-phenylalanine was studied. An inhibitory effect of penicillin G and of ampicillin was demonstrated, whereas chloramphenicol gave rise to an enhancement of the chemiluminescence response from polymorphonuclear leukocytes. These effects could be due to interaction between the drugs and the polymorphonuclear leukocytes, but they could also be the result of interference with the generation of light without any effect on the cells. Therefore, the effects of the same antimicrobial agents on the chemiluminescence generated from a cell-free system consisting of myeloperoxidase and hydrogen peroxide were investigated in parallel. The results obtained in the cell-free system were almost identical to those obtained in the cell system; i.e., penicillin G and ampicillin caused an inhibition and chloramphenicol caused an enhancement of the light emission. These results indicate that observed effects induced by drugs in a chemiluminescence assay are not necessarily due to interaction between the drug and polymorphonuclear leukocytes but may be caused by interference with other components of the assay. In view of these findings, the conflicting data reported in the literature on the effects of antimicrobial agents on phagocyte function are discussed.
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PMID:Influence of antibiotics on formylmethionyl-leucyl-phenylalanine-induced leukocyte chemiluminescence. 360 75

As part of a study of the effects of antibiotic therapy upon human phagocytes, ampicillin and cefaclor were each administered orally to nine healthy adult subjects in a single dose of 500 mg. There was a significant difference in their effects on neutrophil myeloperoxidase (MPO) (EC.1.11.1.7) activity (P less than 0.05) in that ampicillin depressed, but cefaclor enhanced, the measured enzyme activity. Concomitantly ampicillin decreased but cefaclor increased, the rate of phagocytosis of staphylococci, the effects of the two antibiotics also being significantly different (P less than 0.05). Direct measurements of intracellular killing of staphylococci did not change. In four patients with chronic bacterial infections who had low levels of neutrophil MPO activity, treatment with cefaclor led to a significant increase in the MPO levels to within the normal range. Three patients responded satisfactorily to cefaclor despite having previously filed to respond to antibiotics which were similarly active in vitro against the causative bacteria. These findings lead us to suggest that, in patients with chronic refractory infections, attention must be given to the effect of drugs on the host defences in addition to a careful choice of the most active antibacterial agent.
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PMID:Effect of two antibiotics on human granulocyte activities. 630 30

Displacement of bilirubin bound to human serum albumin by ampicillin, indomethacin, chlorpromazine, gentamicin, methylparaben, and propylparaben was investigated quantitatively. Two methods were used in vitro: measurement of bilirubin displacement by studying the rate of bilirubin oxidation with hydrogen peroxide and peroxidase and determination of the albumin reserve for binding of bilirubin by observation of the dialysis rate of an added trace amount of a deputy ligand monoacetyldapsone (p-acetamido-p'-aminodiphenyl sulfone). The latter method was also used for the determination of the albumin reserve in sera from treated newborn infants. The following doses were given: ampicillin, 100 mg/kg iv; indomethacin, 0.2 mg/kg iv; chlorpromazine hydrochloride, 0.7 mg/kg im; gentamicin sulfate, 2.5 mg/kg im. The parabens were present in injectable preparations of chlorpromazine and gentamicin and were therefore given in the following doses: methylparaben, 0.35 mg/kg, and propylparaben, 0.05 mg/kg. All drugs were given in a single dose. A few additional additives and metabolites were studied in vitro. Ampicillin, given to 19 infants, produced a small, significant decrease in plasma albumin reserve, to 82% of the pretreatment level and, thus, had a slight bilirubin-displacing effect, quantitatively consistent with a weak displacing effect measured in vitro. None of the other substances showed any measurable displacement in vivo, likewise in agreement with the results from in vitro studies.
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PMID:Bilirubin-displacing effect of ampicillin, indomethacin, chlorpromazine, gentamicin, and parabens in vitro and in newborn infants. 684 76

Two separate acute bacterial exacerbations of chronic bronchitis or chronic asthmatic bronchitis were treated in 20 patients in a double-blind crossover study. One course of treatment consisted of 320 mg of trimethoprim (TMP) plus, 1,600 mg of sulfamethoxazole (SMZ) daily and the other of 2 g of ampicillin daily; each drug was given for 14 days. Patients were observed initially, twice a week during therapy, and weekly after therapy. Observations that were recorded included graded chest symptoms and physical findings, vital signs, pulmonary function, hematologic parameters, and objective sputum measurements (daily volume, purulence, differential quantitative cytology, quantitative bacterial counts, physical properties, levels of lactate dehydrogenase with its isoenzymes, levels of myeloperoxidase, and presence of deoxyribonucleic acid fibers). Both antibiotic regimens were effective in resolving these acute bacterial exacerbations. Paired t-test analysis revealed few and minor differences between TMP-SMZ and ampicillin during therapy, although three patients did not complete TMP-SMZ therapy because of adverse reactions. However, the period between the two bacterial exacerbations was significantly longer after ampicillin therapy. Innovative in this investigation are the study design and the objective quantitative measurements of inflammatory response and bacterial populations in sputum.
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PMID:Comparison of trimethoprim-sulfamethoxazole with ampicillin in acute infectious exacerbations of chronic bronchitis: a double-blind crossover study. 705 Dec 44

To determine whether the macrolide antibiotic erythromycin prevents microvascular leakage produced by lipopolysaccharide (LPS), we studied tracheae and lungs of pathogen-free rats. Tracheal vascular permeability and neutrophil recruitment were assessed by the percent area occupied by Monastral blue-labeled blood vessels and by myeloperoxidase-containing granulocytes, respectively, in tracheal whole mounts. Pulmonary microvascular leakage was evaluated by lung wet-to-dry (W/D) weight ratio. Inhalation of Escherichia coli LPS (5 mg/kg) caused time-dependent increases in tracheal vascular permeability, neutrophil influx, and lung W/D ratio. These responses were inhibited by pretreatment with oral erythromycin, but not by ampicillin or cefaclor, in a dose-dependent manner: erythromycin at 10 mg/kg daily for 1 wk reduced the area density of Monastral blue-labeled vessels from 6.7 +/- 1.2 to 1.4 +/- 0.3% (p < 0.01), the number of neutrophils (from 365 +/- 51 to 149 +/- 30 cells/mm2, p < 0.01), and lung W/D weight ratio (from 6.76 +/- 0.30 to 5.39 +/- 0.21, p < 0.01). This inhibitory effect of erythromycin was abolished by depletion of circulating neutrophils with cyclophosphamide. These results suggest that LPS causes acute lung injury, microvascular leakage, and neutrophil recruitment in the trachea, and that erythromycin protects against these changes, probably by acting on neutrophils.
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PMID:Effect of erythromycin on endotoxin-induced microvascular leakage in the rat trachea and lungs. 773 18

Interaction of lactoferrin (Lf) with the cell envelope (CE) and outer membrane (OM) of Salmonella typhimurium-type strain ATCC13311 was tested by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western-blot analyses. The peroxidase-labeled bovine Lf (BLf) and human Lf both recognized a heat-modifiable protein with an estimated molecular mass of 38 kD in the OM. Simultaneous immunoblotting with an antiporin monoclonal antibody specific for a conserved porin domain in members of enterobacteriaceae confirmed that the Lf-binding protein is a porin. Such Lf-binding porin proteins (37-39 kD range) were readily detected in nine other common Salmonella species: S. dublin, S. panama, S. rostock, S. abony, S. hartford, S, kentucky, S. pullorum, S. thompson, and S. virchow. The latter six species also demonstrated one to three weak Lf-reactive bands of low molecular weight in their CE. The antibiotic susceptibility of Salmonella in the presence of Lf was examined. A mixture containing sub-minimum inhibitory concentration (MIC) levels of Lf (MIC/4) and cefuroxime (MIC/2) inhibited the bacterial growth. Lf strongly potentiated the action of erythromycin (eightfold), whereas it increased the activity only by two-fold for ampicillin, ciprofloxacin, chloramphenicol, and rifampicin; similarly, these antibiotics also reduced the MIC of BLf by twofold in S. typhimurium. Such antimicrobial potentiation was not observed with BLf mixtures containing cefalexin, gentamycin, or polymyxin B against strain ATCC13311. BLf and cefuroxime also demonstrated potentiation of varying degrees (two to 16-fold) with nine other Salmonella species. These data established the binding of Lf to porins in salmonellae and a potentiation effect of Lf with certain antibiotics.
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PMID:Lactoferrin interaction with salmonellae potentiates antibiotic susceptibility in vitro. 786 7

A new reagent for the detection of penicillin-binding proteins (PBPs) was developed. An N-hydroxysuccinimide ester of biotin was used to tag beta-lactam antibiotics with free side chain amino groups such as ampicillin (BIO-AMP), 6-aminopenicillanic acid (BIO-APA), and 7-aminocephalosporanic acid (BIO-ACA). Bacterial PBPs from cells or isolated cytoplasmic membranes of Escherichia coli, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae were labeled with BIO-AMP, subjected to electrophoresis on sodium dodecyl sulfate (SDS)-polyacrylamide gels, and transferred onto nitrocellulose membranes. Electrophoretic PBP profiles were detected on blots, using colorimetric or chemiluminescence systems, on the basis of the interaction of BIO-AMP-PBP complexes and a streptavidin-peroxidase conjugate. The chemiluminescent reaction permitted a high sensitivity of detection, and PBP profiles could be determined within seconds. All PBP profiles were similar to those obtained with a traditional PBP labeling technique with 125I-labeled penicillin V, except that an additional unidentified PBP (approximately 55,000 Da) was labeled with BIO-AMP in E. coli and H. influenzae. Differences in the intensities of labeling for specific PBPs were observed between the chemiluminescent and radioactive labeling agents and were attributed to the differences in their affinities for PBPs. Similarly, BIO-AMP, BIO-APA, and BIO-ACA produced different PBP profiles. We also investigated the use of BIO-AMP in PBP purification. BIO-AMP-PBP complexes from a mixture of H. influenzae proteins were allowed to bind to avidin immobilized on an agarose support in a microcentrifuge tube. After several washes in the presence of salts, PBPs were eluted by boiling and treatment with SDS. The eluted proteins were separated by electrophoresis on SDS-polyacrylamide gels, and biotinylated proteins were identified on blots by a chemiluminescence reaction. Biotinylation of beta-lactams is rapid, safe, and inexpensive. Our results demonstrate the feasibility of using biotinylated beta-lactams as nonradioactive reagents for the study of PBPs and for the purification of these proteins.
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PMID:Use of biotinylated beta-lactams and chemiluminescence for study and purification of penicillin-binding proteins in bacteria. 806 79

Luminol-enhanced luminescence is a method used to measure formation of reactive oxygen intermediates important in the ability of neutrophils to kill microbes. Several studies have demonstrated that under some conditions of incubation, ampicillin can inhibit neutrophil-derived luminol-enhanced luminescence. We evaluated the mechanism(s) by which ampicillin inhibited the luminescent response of stimulated neutrophils. We also investigated sulbactam, a beta-lactamase inhibitor which has been given in combination with ampicillin and other beta-lactam antibiotics to increase their spectra, for possible similar effects. Both ampicillin and sulbactam attenuated luminol-enhanced luminescence by approximately 40%. Superoxide production was not prevented by added ampicillin, nor was superoxide scavenged by it. Myeloperoxidase reacts with H2O2 and Cl- to generate OCl-, which is believed to be the oxidizer of luminol that is primarily responsible for enhancement of neutrophil-derived luminescence. Hydroxyl radicals (HO.), which may also oxidize luminol, resulting in luminescence, can be formed from O2- and H2O2 via either myeloperoxidase-dependent (involving intermediate OCl-) or myeloperoxidase-independent (through a metal ion catalyst) reactions. Ampicillin scavenged H2O2 and OCl- and prevented 95% of Fenton reaction-generated HO. from reacting with 5,5-dimethyl-1-pyrroline-N-oxide. Sulbactam was found to scavenge OCl- and HO., but less avidly than ampicillin did. Neither ampicillin nor sulbactam inhibited myeloperoxidase activity. Sublethal concentrations of sulbactam had no significant effect on neutrophil killing of Staphylococcus aureus and Escherichia coli. Our results demonstrate a mechanism(s) by which ampicillin inhibits luminol-enhanced luminescence from stimulated neutrophils, namely, through scavenging of the oxidant(s) primarily responsible for the generation of luminescence.
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PMID:Oxidant-scavenging activities of ampicillin and sulbactam and their effects on neutrophil functions. 839 Aug 14


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