Antimicrobial evaluation of new metallic complexes with xylitol active against P. aeruginosa and C. albicans: MIC determination, post-agent effect and Zn-uptake.

Xylitol (xylH5) is metabolized via the pentose pathway in humans, but it is unsuitable as an energy source for many microorganisms where it produces a xylitol-induced growth inhibition and disturbance in protein synthesis. For this reason, xylitol is used in the prophylaxis of several infections. In the search of better antimicrobial agents, new copper and zinc complexes with xylitol were synthesized and characterized by analytical and spectrosco pic methods: Na2[Cu3(xylH−4)2]·NaCl·4.5H2O (Cu-xyl) and [Zn4(xylH−4)2(H2O)2]·NaCl·3H2O (Zn-xyl). Both copper and zinc complexes presented higher MIC against Pseudomona aeruginosa than the free xylitol while two different behaviors were found against Candida albicans depending on the complex. The growth curves showed that Cu-xyl presented lower activity than the free ligand during all the studied period. In the case of Znxyl the growth curves showed that the inhibition of the microorganism growth in the first stage was equivalent to that of xylitol but in the second stage (after 18 h) Zn-xyl inhibited more. Besides, the PAE (post agent effect)obtained for Zn-xyl and xyl showed that the recovery from the damage of microbial cells had a delay of 14 and 13 h respectively. This behavior could be useful in prophylaxis treatments for infectious diseases where it is important that the antimicrobial effect lasts longer. With the aim to understand the microbiological activities the analysis of the particle size, lipophilicity and Zn uptake was performed.

Nitric oxide inhibits development of embryos and implantation in mice.

The objectives of this study were to evaluate the effects of a nitric oxide (NO) donor on embryo development in vitro and on implantation of embryos in vivo in mice. Mouse embryos (2-cell) were incubated in media containing different concentrations of diethylenetriamine/NO (DETA/NO), a nitric oxide donor, and development was monitored daily for 4 days. Specificity of NO effects was assessed by using DETA without NO or 48 h preincubated DETA/NO. In in-vivo studies, mated mice were continuously infused, subcutaneously, with various concentrations of DETA/NO or DETA through mini-osmotic pumps (from day 1 of pregnancy), and implantations in the uterus were assessed on day 6. None of the embryos progressed beyond 4-cell stage when exposed to 0.1 or 1.0 mM DETA/NO compared with 94.5% of control embryos that developed beyond the morula stage by day 4. Embryo development was unaffected by lower (0.001 and 0.01 mM) concentrations of DETA/NO, 48 h preincubated DETA/NO, or DETA only. Infusion of DETA/NO to mice caused inhibition of embryo implantation in a dose-dependent manner. No implantation sites were observed in mice infused with a daily dose of 20 micromol DETA/NO rate, compared with an implantation rate of 81.8% in control or DETA-treated mice. This study demonstrates for the first time that higher concentrations of NO inhibit both embryo development in vitro and implantation in vivo in mice.