There are currently no defined optimal therapies available for multidrug-resistant (MDR) Acinetobacter baumannii infections. We evaluated the efficacy of rifampin, imipenem, sulbactam, colistin, and their combinations against MDR A. baumannii in experimental pneumonia and meningitis models. The bactericidal in vitro activities of rifampin, imipenem, sulbactam, colistin, and their combinations were tested using time-kill curves. Murine pneumonia and rabbit meningitis models were evaluated using the A. Acinetobacter baumannii is an important nosocomial pathogen worldwide (5, 35), with pneumonia, bacteremia, and surgical site and urinary tract infections being the most important infections caused by this organism (16). A Spanish study showed A. baumannii as the cause of nearly 9% of cases of ventilator-associated pneumonia (VAP) (2), with a crude mortality of 40% to 70% (14). A. baumannii may also cause meningitis and ventriculitis, especially in patients undergoing neurosurgical procedures or with head trauma (17), with mortality rates between 20% and 27% (5).The well-known ability of A. baumannii to acquire resistance to almost all groups of available antibiotics leads to serious problems in the management of infections caused by multidrug-resistant (MDR) A. baumannii infections (5, 16). In these cases, carbapenems have been considered the treatment of choice. However, increasing numbers of carbapenem-resistant A. baumanii isolates have been reported worldwide (1, 28), prompting the search for other therapeutic options.Sulbactam has been used successfully in cases of meningitis and pneumonia caused by A. baumannii (17,21,39). Colistin has good in vitro activity (37) but has shown contradictory results in clinical practice (12) and experimental models (23). Rifampin has demonstrated in vitro and in vivo bactericidal activities against MDR A. baumannii in an experimental pneumonia model (23), but rifampin-resistant mutants appear shortly after treatment initiation with rifampin alone (23, 27). The combination of rifampin plus imipenem has been evaluated in clinical infections caused by highly imipenem-resistant A. baumannii strains, with inconclusive results (33). Two clinical studies have shown efficacy rates of 76% to 100% for colistin plus rifampin in VAP, bacteremia, and meningitis (4, 25). The aims of this study were to evaluate the efficacies of rifampin and its combinations with imipenem, sulbactam, and colistin in experimental pneumonia and meningitis models caused by MDR A. baumannii strains.

Simvastatin promotes intracellular antioxidant systems, fundamentally SOD, restoring endothelial function but not having any effect on blood pressure.

No abstract

1 The effects of oral administration of the HMG-CoA reductase inhibitor, simvastatin (SV), on agerelated endothelial dysfunction were investigated in the aorta of male Wistar rats. 2 Adult (12-14 weeks) and old (60-80 weeks) rats were treated daily for 12 weeks with either vehicle or SV (1 mg kg À1 ). In old rats, SV treatment did not significantly affect systolic blood pressure and LDL-cholesterol, but it reduced plasma cholesterol, triglycerides and oxidised LDL though it did not affect total antioxidant status. 3 SV improved endothelium-dependent relaxation to acetylcholine and A-23187 in vessels from aged, but not adult, rats. This effect was linked to a greater NO vasodilatation via an increased expression of endothelial NO-synthase. A mechanism sensitive to superoxide dismutase and catalase also accounts for enhanced endothelial vasodilatation. 4 Finally, SV did not affect the release of prostacyclin, but it inhibited the generation of thromboxane (TX) A 2 from COX-2 isoform. The effect of the latter was sensitive to the T p receptor antagonist, 605. 5 The present study provides evidence that oral administration of SV improves endothelial dysfunction in the aorta from aged rats by mechanisms associated with enhanced NO vasodilatation, reduced release of TXA 2 from cyclo-oxygenase, and increased antioxidant properties of the vessel wall. These data underscore a new therapeutic perspective for SV in age-related endothelial dysfunction.

BIB induces a temporary sense of satiety in morbidly obese patients which is not mediated by modification of fasting or postprandial levels of plasma ghrelin.

No abstract

The effect of simultaneous plasma concentrations of pegylated interferon-alpha-2a (pegIFN-alpha-2a) and ribavirin (Rbv) on viral response has not been addressed to date. Hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfected patients received pegIFN-alpha-2a and Rbv under routine clinical care conditions. Plasma concentrations of the two drugs were measured using enzyme-linked immunosorbent assay and high-performance liquid chromatography after 2, 4, 8, and 12 weeks and at the end of the treatment period (24-48 weeks, according to HCV genotype and treatment duration). Large interindividual variability was observed in the plasma levels of both drugs. After multivariate analysis, only HCV genotype 3, low HCV-RNA levels, and pegIFN-alpha-2a exposure remained as independent factors associated with sustained viral response (SVR). The probability of attaining an SVR in HCV genotypes 1 and 4 was more than three to four times higher in patients with pegIFN-alpha-2a levels above the selected cutoff point. Early therapeutic drug monitoring of pegIFN-alpha-2a levels could be beneficial in improving current treatment outcomes.

A biomarker is generally an analyte that indicates the presence and/or extent of a biological process, which is in itself usually directly linked to the clinical manifestations and outcome of a particular disease. The biomarkers in the field of lysosomal storage diseases (LSDs) have particular relevance where spectacular therapeutic initiatives have been achieved, most notably with the introduction of enzyme replacement therapy (ERT). There are two main types of biomarkers. The first group is comprised of those molecules whose accumulation is directly enhanced as a result of defective lysosomal function. These molecules represent the storage of the principal macro-molecular substrate(s) of a specific enzyme or protein, whose function is deficient in the given disease. In the second group of biomarkers, the relationship between the lysosomal defect and the biomarker is indirect. In this group, the biomarker reflects the effects of the primary lysosomal defect on cell, tissue, or organ functions. There is no “gold standard” among biomarkers used to diagnosis and/or monitor LSDs, but there are a number that exist that can be used to reasonably assess and monitor the state of certain organs or functions. A number of biomarkers have been proposed for the analysis of the most important LSDs. In this review, we will summarize the most promising biomarkers in major LSDs and discuss why these are the most promising candidates for screening systems.