Identification of New Natural CphA Metallo-β-Lactamases CphA4 and CphA5 in Aeromonas veronii and Aeromonas hydrophila Isolates from Municipal Sewage in Central Italy

Two new natural CphA metallo-β-lactamases, the CphA4 and CphA5 enzymes, were identified in water samples from municipal sewage in central Italy. Compared to CphA, the CphA4 and CphA5 enzymes showed numerous point mutations. These enzymes have a narrow spectrum of substrates focused on carbapenems only. CphA5 showed k_cat values about 40-, 12-, and 97-fold higher than those observed for CphA4 versus imipenem, ertapenem, and biapenem, respectively.     

Age-specific prevalence,transmission and phylogeny of TT virus in the Czech Republic

Background  

TT virus is prevalent worldwide, but its prevalence and genotype distribution in Central and East-Europe has not been determined. The high prevalence of TTV in multiply-transfused patients points to the importance of a parenteral mode of transmission, but since more than half of the general population is infected other possible routes of transmission must be considered.     

Total administered dose of ibandronate determines its effects on bone mass and architecture in ovariectomized aged rats

OBJECTIVE: Ibandronate is a highly potent nitrogen-containing bisphosphonate that can prevent bone loss in various animal models as well as in clinical trials. We evaluated the effects of different doses and treatment schedules in ovariectomized aged rats, a model of human osteoporosis. METHODS: Eight-month-old female Wistar rats were ovariectomized or sham operated (n = 15/group). Doses of 0.1 to 30 microg/kg/day ibandronate were administered subcutaneously over a period of 20 weeks with or without a 5 times higher single loading dose starting one day postsurgery. In a subsequent experiment, the optimal preventive dose, which is the lowest dose that prevented bone loss completely, or a suboptimal preventive dose were administered over the same period, either daily or by 3 cyclical intermittent regimens (on/off weeks = 1/2, 1/4, and 1/6), resulting in the same cumulative total dose. RESULTS: Ovariectomy induced significant bone loss in the following primary endpoints: femoral radiographic density, dry weight/tissue volume, and calcium content/tissue volume. Histomorphometry in the tibia resulted in reduced trabecular bone mass, thickness, and number, and increased separation. The optimal dose was 1.0 microg/kg/day, while 0.1 microg/kg/day was suboptimal. Higher doses resulted in a plateau. The loading dose had no effect on the results. Cyclical intermittent administration dose-dependently prevented bone loss, providing equivalent results per total dose, irrespective of the administration schedule. CONCLUSION: There were no differences between the various regimens, suggesting that it is the total dose of ibandronate rather than the treatment schedule that is important for efficacy, at least within the tested dosing intervals.