Simvastatin reverses cyclosporin A-induced endothelial damage in rats: lipid-lowering-dependent and -independent effects

Cydosporin A [CyA] is the immunosuppressant most frequently used in transplant surgery and in the management of autoimmune diseases. CyA-induced oxidative stress together with dyslipidemia have been implicated in the pathogenesis of vascular dysfunction associating CyA therapy. The present study investigated the possible protective effect of simvastatin, a lipid-lowering drug with potent antioxidant properties, against CyA-induced endothelial damage in male rats. Eighteen male Wistar rats were used. They were divided into 3 groups: control, CyA and CyA + simvastatin. In the control group, rats were administered the vehicle, olive oil; in the CyA group, rats were administered CyA [20 mg/kg/day, s.c. for 14 days] and in the CyA+simvastatin group, rats were co-administered simvastatin [2.5 mg/kg/day, s.c. for 14 days] and CyA. Administration of CyA [20 mg/kg/day, s.c. for 14 days] in male rats resulted in a significant increase in the lipid peroxidation product, malondialdehyde [MDA], and a significant decrease in superoxide dismutase [SOD] activity in plasma. CyA treatment was also associated with a significant increase in plasma nitrite level as well as an elevation in plasma cholesterol, triglycerides [TGs], low density lipoproteins [LDL] and a reduction in high density lipoproteins [HDL] levels. CyA-induced vascular dysfunction was further confirmed by the attenuation of endothelium-dependent relaxations produced by carbachol in rat isolated aortic rings. Co-administration of simvastatin [2.5 mg/kg/day, s.c. for 14 days] with CyA significantly reversed the deleterious biochemical and functional vascular effects that accompanied CyA treatment. The present study provides good evidence that both oxidative stress and dyslipidemia underlie the CyA-induced vascular damage, an effect that could be reversed by simvastatin co-administration

Evaluation of different phenotypic methods for detection of methicillin [oxacillin] resistance in coagulase-negative staphylococci

Coagulase-negative staphylococci [CNS] are one of the major causes of nosocomial infections. Methicillin [oxacillin] resistant strains are particularly important because they narrow therapeutic options. Detecting methicillin resistance among CNS has been a challenge for years. The objective of this study was to evaluate the ability and accuracy of four phenotypic methods, disk diffusion [DD]; agar screening plate with 6 micro g of oxacillin per ml [OXA]; E-test and the MRSA-Screen latex agglutination test [Denka-Seiken, Tokyo, Japan], to determine the susceptibility of CNS to oxacillin. The methods were evaluated by using the presence of the mecA gene, as detected by PCR, as the "gold standard". One hundred and ninety seven strains of CNS of 7 species were analysed. 49.2% were mecA positive. For the different methods evaluated, the sensitivities and specificities were as follows: for disk diffusion, 93.8 and 93%, respectively; for the agar screen test 95.9 and 98%, respectively; for E-test, 100 and 95%, respectively; and for the slide latex agglutination test, 96.9 and 100%, respectively. The latex agglutination test sensitivity was increased to 100% when retested after induction. In conclusion, all of the phenotypic methods evaluated in the present study appeared to perform very well for the detection of oxacillin resistance in CNS. The MRSA-Screen latex agglutination test was not only the most sensitive, specific and accurate method but also rapid and technically simple method to be applied in routine laboratories for the detection of oxacillin resistance which is mediated by the mecA gene

Slime forming staphylococcus epidermidis isolated from orthopedic prosthesis infections and its sensitivity to antibiotics

Staphylococcus epidermidis [S.epidermidis] is a frequent cause of infections of indwelling medical devices especially those with orthopedic implants. S.epidermidis grows on medical devices as an adherent biofilm consisting of cells enmeshed in a sticky, extracelluar slime that is firmly attached to the underlying surface. The slim matrix makes S.epidermidis biofilm highly resistant to antibiotics and host defenses and nearly impossible to eradicate. The aim of the study is to determine importance of slime formation in S. epidermidis orthopedic prosthesis infections and to investigate if slime formation has an effect on its antibiotics sensitivity. 80 coagulase negative staphylococcus strains [CoNS] were isolated from 200 tissue specimens of patients with orthopedic prothesis infections. Out of these 80 CoNS, 52 [65%] strains were S.epidermidis. Isolated S. epidermidis were plated on Congo red agar and subjected to PCR to detect icaA and icaD genes to identify and confirm slime producing strains respectively. All biofilm producing strains were subjected to MIC and MBEC using Calgary Biofilm Device[CBD]. 36 [69%] S. epidermidis strains were slime [biofilm] producers and 16 [31%]strains were non slime [non biofilm] producers by CRA, while by PCR 39[75%] strains of S. epidermidis were biofilm producers and 13 [25%] strains were non biofilm producers. The results also revealed that the minimal biofilm eradication concentrations [MBECs] were higher than the corresponding conventionally determined MICs for all antibiotics tested. MIC 50 and MBEC 50 for vancomycin, were 2 micro g/ml versus 8 micro g/ml, gentamycin, 1 micro g/ml versus 32 micro g/ml, oxacillin, 4 micro g/ml versus 16 micro g/ml, erythromycin, 8 micro g/ml versus 64 micro g/ml, ciprofloxacin, 0.5 micro g/ml versus 2 micro g/ml and cephalothin 4 micro g/ml versus 16 micro g/ml. MIC90 and MBEC90 for vancomycin were 4 micro g/ml versus16 micro g/ml, gentamycin, 16 micro g/ml versus 128 micro g/ml, oxacillin, 8 micro g/ml versus 128 micro g/ml, erythromycin, 16 micro g/ml versus 128 micro g/ml, ciprofloxacin, 4 micro g/ml versus 8 micro g/ml and cephalothin 32 micro g/ml and 128 micro g/ml. The results of the present study confirm that ica genes can be considered a virulence marker in the pathogenesis of implant associated orthopedic infection by S. epidermidis. This study also demonstrates marked differences between the results of susceptibility testing performed according to standard NCCLS guidelines and testing based on biofilm susceptibility testing