Daptomycin is a new biosynthetic antibiotic which belongs to a new class of drugs known as lipopeptides. The objective of this study was to evaluate the effects of daptomycin and vancomycin on tobramycin-induced nephrotoxicity. Female Sprague-Dawley rats were treated during 4 and 10 days with either saline (NaCl, 0.9%) or tobramycin at doses of 4 and 40 mg/kg per day (given every 12 h [ql2h] intraperitoneally). Each treatment was combined with saline, daptomycin at a dose of 20 mg/kg per day (given ql2h subcutaneously), and vancomycin at a dose of 50 mg/kg per day (given ql2h subcutaneously). Daptomycin and vancomycin had no effect on the intracortical accumulation of tobramycin. The nephrotoxicity of aminoglycosides has been intensively studied, but there are limited data on the mechanism of vancomycin toxicity. The nephrotoxicity of vancomycin given alone has been demonstrated in animals by using sensitive parameters of nephrotoxicity (22). It has also been shown in both human (11,32) and animal (22,23,36,38) studies with different animal strains and drug doses that nephrotoxicity is increased when vancomycin and an aminoglycoside are injected concomitantly. However, this phenomenon is not reproduced in pediatric populations (27,33). Moreover, it has also been observed that vancomycin and aminoglycosides accumulate within the renal cortices of experimental animals (22,23,38

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Purpose: To assess the impact of bariatric surgery and an added supervised exercise training programme on heart rate variability (HRV) in patients with severe obesity. Methods: Fifty-nine patients who underwent bariatric surgery were randomised in the postoperative period to a 12-week supervised exercise training programme (moderate intensity combination aerobic/resistance exercise training programme) or a control group. Indices of HRV including time-domain, spectral-domain, and nonlinear parameters were measured preoperatively, and at 3, 6, and 12 months. Results: After the surgical procedure, both groups improved anthropometric parameters. Type 2 diabetes, hypertension, and dyslipidemia resolutions were similar between groups. Total body weight loss at 6 and 12 months were also comparable between groups (6 months: 28 ± 6 vs. 30 ± 6%; 12 months: 38 ± 9 vs. 38 ± 10%; control vs. intervention group respectively). Bariatric surgery improved HRV parameters at 12 months compared to the pre-operative values in the intervention group: standard deviation of R-R interval (SDNN) (156.0 ± 46.4 vs. 122.6 ± 33.1 ms), low frequency (LF) (6.3 ± 0.8 vs. 5.8 ± 0.7 ms 2 ), and high frequency (HF) (5.1 ± 0.8 vs. 4.7 ± 0.9 ms 2 ) (all p<0.001). For the control patients, similar improvements in SDNN (150.0 ± 39.4 vs. 118.8 ± 20.1 ms), LF (6.1 ± 0.9 vs. 5.7 ± 0.8 ms 2 ), and HF (5.0 ± 0.9 vs. 4.7 ± 0.9 ms 2 ) were obtained (all p<0.001). However, there was no add-on impact of the supervised exercise training programme on HRV after 12 months (p>0.05 for all HRV parameters). Conclusion: Bariatric surgery is associated with an improvement in HRV. A supervised exercise training programme in the post-operative period did not modulate further the benefits of bariatric surgery regarding HRV parameters.

Many risk factors associated with aminoglycoside nephrotoxicity have been identified in humans and experimental animals. They include an initial high rate of creatinine clearance, high initial peak levels in serum, age, sex, duration of therapy, liver disease, and renal infection. The concomitant administration of steroids has never been investigated. We evaluated the role of hydrocortisone on gentamicin-induced nephroxicity in a model of infused rats. We showed that hydrocortisone given over 3 days after the infusion did not modify the gentamicin half-life in the renal cortex, gentamicin-induced lysosomal phospholipidosis, or histopathology but did reduce significantly the 3H/DNA ratio on day 4 after gentamicin infusion. We concluded that hydrocortisone interferes with the postnecrotic cellular regeneration process, an important step that is responsible for the recovery of normal kidney structure and function following toxic injuries associated with aminoglycoside therapy.Eliminated essentially by glomerular filtration, aminoglycosides are partially reabsorbed by proximal tubular cells through absorptive endocytosis (pinocytosis) into small vesicles that fuse with primary lysosomes (11,28). These primary lysosomes transfer the aminoglycoside to secondary lysosomes, where storage occurs independently of the duration of treatment (11). These drugs induce a lysosomal phospholipidosis characterized by inhibition of sphingomyelinase and phospholipase A1 activity and by phospholipid accumulation into lysosomes (17). This lysosomal phospholipidosis is accompanied by cellular necrosis and postnecrotic cell regeneration (10,18,20).Many risk factors associated with aminoglycoside nephrotoxicity have been identified in humans. They are an initial high rate of creatinine clearance, high initial peak levels in serum, age, sex, duration of treatment, and liver disease (23,26). In animals, dose and frequency (4), age (21, 22), sex (3,15), concomitant use of vancomycin (32), and renal infections (2) are clearly recognized as risk factors. The role of antiinflammatory agents like hydrocortisone on aminoglycoside nephrotoxicity is unknown. Steroids and nonsteroidal antiinflammatory agents are frequently administered with antibiotics to patients suffering from severe localized infections. In addition to their mineral and glucocorticoid effects, it has been shown that steroids suppress DNA synthesis in the livers of growing rats (6, 14) and in various nonlymphoid tissue of the weanling rats (19) and inhibit mitosis in various cells in tissue cultures (12).The objective of the present study was to evaluate the role of hydrocortisone on the pathophysiology of gentamicin nephrotoxicity. Special attention was focused on the effect of hydrocortisone on renal tubular epithelial cells undergoing renewal and repair. MATERIALS AND METHODSFemale Sprague-Dawley rats (weight, between 200 and 250 g) were used in this study. They were housed singly and had free access to food and water throughout the experiment. Gentamicin was infused over a 12...