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Inhibitory effects of phosphodiesterase 5 inhibitor, tadalafil, on mechanosensitive bladder afferent nerve activities of the rat, and on acrolein-induced hyperactivity of these nerves.


Enterococcus mundtii ST4SA and Lactobacillus plantarum 423 produce bacteriocins with activity against a number of Gram-positive and Gram-negative bacteria. Both strains survived intestinal conditions simulated in a gastro-intestinal model (GIM) with infant milk formulations as substrate and prevented the growth of Listeria monocytogenes ScottA. The strains are inhibited by the antibiotics amoxicillin, cefadroxil, roxithromycin and doxycycline, anti-inflammatory medicaments containing meloxicam, ibuprofen and sodium diklofenak, and analgesics containing paracetamol, codeine phosphate and promethazine. Strain 423 is sensitive to vancomycin and does not contain genes encoding gelatinase, cell aggregation substance (AS), adhesion to collagen (Ace), enterococcus surface protein (Esp), Enterococcus faecalis endocarditis antigen (EfaAfs), cytolysin and non-cytolysin (beta-hemolysin III). Genes encoding AS, cytolysin and non-cytolysin (beta-hemolysin III) were amplified from the genome of strain ST4SA. Survival of strains ST4SA and 423 improved when used as combined cultures in the GIM and compared well with the survival of commercially available probiotics subjected to the same conditions.

The increasing resistance of E. coli to trimethoprim makes this drug less suitable for empiric treatment of UTI. Young children with UTI seem predisposed to early development of resistance. Therefore, surveillance of resistance to antimicrobials with special regard to age and gender is recommended.

Pept2 knockout mice are an important tool to evaluate the evolving role and relevance of this proton-coupled oligopeptide transporter beyond drug disposition, where the transporter also modulates the pharmacodynamic and toxicodynamic effects of drug substrates. Our in vivo studies with glycylsarcosine in Pept2 knockout mice have established "proof of concept" that PEPT2 can have a significant effect on dipeptide disposition. Subsequent studies with the aminocephalosporin antibiotic cefadroxil have shown relevance to pharmacology and infectious disease. Finally, studies with the endogenous peptidomimetic 5-aminolevulinic acid have demonstrated relevance to toxicology in the framework of porphyria- and lead-induced neurotoxicity. These studies have consistently demonstrated the dual action of PEPT2 with respect to its apical localization in choroid plexus epithelium and kidney in: 1) effluxing substrates from CSF into choroid plexus, thereby affecting regional pharmacokinetics in brain; and 2) reabsorbing substrates from renal tubular fluid into proximal tubules, thereby affecting systemic pharmacokinetics and exposure. Moreover, these studies have shown that the regional effect of PEPT2 in limiting substrate concentrations in the CSF is more dramatic than its effect in increasing systemic exposure. In the case of 5-aminolevulinic acid, such regional modulation of drug disposition translates directly into significant changes in neurotoxicity.

The in vitro susceptibility of human isolates of Pasteurella multocida to oral antimicrobial agents from our current study and from a review of the literature suggests that dicloxacillin (oxacillin), erythromycin, clindamycin, cephalexin, cefaclor, and cefadroxil should not be used for empiric therapy of animal bite wounds. Agents that were consistently active against P. multocida were penicillin, ampicillin, amoxicillin-clavulanic acid, tetracycline, minocycline, chloramphenicol, trimethoprim-sulfamethoxazole, and cefuroxime. Possible reasons for the confusion regarding the activity of oral cephalosporins are addressed.

The in-vitro activity of Ro-15-8074, a new oral cephalosporin, was tested against common clinical isolates, and compared with the in-vitro activity of cefaclor, cefadroxil, ampicillin and co-trimoxazole. Its activity against Enterobacteriaceae was better than those of the other antibiotics tested. It was also highly active against Haemophilus influenzae, including beta-lactamase producing strains. Its activity against Pseudomonas aeruginosa and Acinetobacter spp., was poor. Ro-15-8074 was less active against staphylococci and group D streptococci than were cefaclor, cefadroxil and ampicillin. It was equally or less active than cefaclor, cefadroxil, ampicillin and co-trimoxazole against other streptococci.

The present study describes the application of CE to investigate the interaction between a cephalosporin, cefadroxil and different metal ions. This study aims at quantifying the interaction of cefadroxil with Zn(2+), Al(3+), Fe(3+), Cu(2+) and Co(2+) ions using the effective electrophoretic mobility as a parameter for calculation of the reaction association constant (K). For this purpose, the electrophoretic mobilities of cefadroxil at different metal ion concentrations in citrate buffer pH 3.6 were determined. A mathematical model to calculate the association constant between cefadroxil and metal ions was used. The results showed that a strong change in the cefadroxil electrophoretic mobility was observed by increasing the metal ion concentrations. The results revealed that by increasing the concentration of metal ions in the running buffer the degree of complexation increases too. On the basis of the results, the strength of the interaction of cefadroxil with the investigated metal ions follows the order Zn(2+)>Cu(2+)>Co(2+)>Fe(3+)>Al(3+). The association constant of the investigated reactions ranged from 451.57 to 1546.52 L/mmol. The results indicate that it is possible to characterize the interaction between cefadroxil and metal ions quantitatively using CE.