Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: KEGG:D02259 (NaI)
 1,823 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cefdinir, a new oral 2-amino-5-thiazolyl cephalosporin, inhibited the luminol-amplified chemiluminescence (LACL) response of human neutrophils stimulated by PMA but not opsonized zymosan, in a concentration-dependent but not time-dependent manner. The LACL response to opsonized zymosan in cytochalasin B-treated neutrophils was, however, inhibited by cefdinir. Various cephalosporins, regardless of the presence of a 2-amino-5-thiazolyl moiety, did not significantly alter the neutrophil LACL response triggered by PMA and zymosan. The LACL response induced by the calcium ionophore A23187 and FMLP was also impaired by cefdinir, and this impairment was increased in cytochalasin B-treated neutrophils. Superoxide anion generation by neutrophils, measured in terms of lucigenin-amplified chemiluminescence and cytochrome c reduction, was not altered. Spontaneous and FMLP-induced neutrophil degranulation, assessed by lysozyme and beta-glucuronidase release, were not modified by cefdinir. Furthermore, cefdinir inhibited LACL generation in cell-free systems consisting of H2O2, NaI, and either horseradish peroxidase or a myeloperoxidase-containing neutrophil extract. Orthodianisidine oxidation in these two acellular systems was inhibited by cefdinir. Cefdinir did not alter neutrophil bacterial killing at concentrations that inhibited myeloperoxidase-containing neutrophil extract-dependent reactions induced by soluble stimuli. Taken together, these data strongly suggest that cefdinir directly inhibits the activity of myeloperoxidase-containing neutrophil extract released into the extracellular medium during neutrophil stimulation by soluble mediators, but has no effect on that released into the phagolysosome during phagocytosis. This unusual property of a member of the beta-lactam family could be of interest in modulating the exaggerated inflammatory process often associated with infectious diseases.
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PMID:Cefdinir (CI-983), a new oral amino-2-thiazolyl cephalosporin, inhibits human neutrophil myeloperoxidase in the extracellular medium but not the phagolysosome. 813 56

Mass Spectra of charge states of folded proteins were obtained with nanospray and aqueous solution containing 20 microM the protein (ubiquitin, cytochrome c, lysozyme) and one of the NaA salts NaCl, NaI, NaAc (acetate) (1-10 mM). At very low collision activated decomposition (CAD), the mass spectra of a protein with charge z exhibited a replacement of zH+ with zNa+ and also multiple adducts of NaA. Higher CAD converts the NaA adduct peaks to Na minus H peaks. These must be due to loss of HA where the H was provided by the protein. The degree of HA loss with increasing CAD followed the order I < Cl < Ac. Significantly, the intensity of the ions with n (Na minus H) adducts showed a downward break past an n(MAX) which is equal to the number of acidic residues of the protein plus the charge of the protein. All the observations could be rationalized within the framework of the electrospray mechanism and the charge residue model, which predict that due to extensive evaporation of solvent, the solutes will reach very high concentrations in the final charged droplets. At such high concentrations, positive ions such as Na+, NH4+ form ion pairs with ionized acidic residues and the negative A- form ion pairs with ionized basic residues of the protein. Adducts of Na+, and NaA to backbone amide groups occur also. This reaction mechanism fits all the experimental observations and provides predictions that the number of acidic and basic groups at the surface of the gaseous protein that remain ionized can be controlled by the absence or presence of additives to the solution.
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PMID:Ion-ion and ion-molecule reactions at the surface of proteins produced by nanospray. Information on the number of acidic residues and control of the number of ionized acidic and basic residues. 1597 26