Simultaneous regulation of lactate production and fatty acid metabolism by Resveratrol in rat Sertoli cells.

Sertoli cells provide structural and nutritional support for germ cell development. They actively metabolize glucose and convert it into lactate, which is an important source of energy for germ cells. They also oxidize fatty acids (FA), stored as triacylglycerides (TAGs) within lipid droplets (LD), to fulfill their own energy requirements. So, the combined regulation of lactate production and FA metabolism may be relevant to the physiology of seminiferous tubules. Resveratrol (RSV) is a nutritional supplement found primarily in red grape skin that exhibits multiple beneficial health effects: it is cardioprotective, anti-inflammatory, anticancer, and antiaging. The aim of this study was to evaluate the effect of RSV in Sertoli cells lactate production and lipid metabolism. Sertoli cell cultures obtained from 20-day-old rats were incubated for different times with 10 or 50 µM RSV. RSV treatment increased lactate production and glucose consumption. These increments were accompanied by a rise in GLUT1 expression, which is the main glucose transporter in Sertoli cells. On the other hand, RSV decreased LD content and TAG levels. In addition, an increase in ATGL and FAT/CD36 mRNA levels was observed, which suggests augmented cytoplasmatic FA availability. RSV treatment also increased P-ACC levels, which might indicate that RSV promotes FA transport into the mitochondria to be oxidized. An enhanced expression of LCAD and MCAD, enzymes that participate in the oxidation of FA, was also observed. Altogether, these results suggest that RSV simultaneously regulates Sertoli cells lactate production and lipid metabolism, ensuring an adequate energetic balance both in germ and Sertoli cells.

Characteristics of prosthetic joint infections due to Enterococcus sp. and predictors of failure: a multi-national study.

The objective of this study was to review the characteristics and outcome of prosthetic joint infections (PJI) due to Enterococcus sp. collected in 18 hospitals from six European countries. Patients with a PJI due to Enterococcus sp. diagnosed between January 1999 and July 2012 were retrospectively reviewed. Relevant information about demographics, comorbidity, clinical characteristics, microbiological data, surgical treatment and outcome was registered. Univariable and multivariable analyses were performed. A total of 203 patients met the inclusion criteria. The mean (SD) was 70.4 (13.6) years. In 59 patients the infection was diagnosed within the first 30 days (29.1%) from arthroplasty, in 44 (21.7%) between 31 and 90 days, in 54 (26.6%) between 91 days and 2 years and in 43 (21%) after 2 years. Enterococcus faecalis was isolated in 176 cases (89%). In 107 (54%) patients the infection was polymicrobial. Any comorbidity (OR 2.53, 95% CI 1.18-5.40, p 0.01), and fever (OR 2.65, 95% CI 1.23-5.69, p 0.01) were independently associated with failure. The only factor associated with remission was infections diagnosed later than 2 years (OR 0.25, 95% CI 0.09-0.71, p 0.009). In conclusion, prosthetic joint infections due to Enterococcus sp. were diagnosed within the first 2 years from arthroplasty in >70% of the patients, almost 50% had at least one comorbidity and infections were frequently polymicrobial (54%). The global failure rate was 44% and patients with comorbidities, fever, and diagnosed within the first 2 years from arthroplasty had a poor prognosis.

Gram-negative prosthetic joint infection: outcome of a debridement, antibiotics and implant retention approach. A large multicentre study.

We aim to evaluate the epidemiology and outcome of gram-negative prosthetic joint infection (GN-PJI) treated with debridement, antibiotics and implant retention (DAIR), identify factors predictive of failure, and determine the impact of ciprofloxacin use on prognosis. We performed a retrospective, multicentre, observational study of GN-PJI diagnosed from 2003 through to 2010 in 16 Spanish hospitals. We define failure as persistence or reappearance of the inflammatory joint signs during follow-up, leading to unplanned surgery or repeat debridement>30 days from the index surgery related death, or suppressive antimicrobial therapy. Parameters predicting failure were analysed with a Cox regression model. A total of 242 patients (33% men; median age 76 years, interquartile range (IQR) 68-81) with 242 episodes of GN-PJI were studied. The implants included 150 (62%) hip, 85 (35%) knee, five (2%) shoulder and two (1%) elbow prostheses. There were 189 (78%) acute infections. Causative microorganisms were Enterobacteriaceae in 78%, Pseudomonas spp. in 20%, and other gram-negative bacilli in 2%. Overall, 19% of isolates were ciprofloxacin resistant. DAIR was used in 174 (72%) cases, with an overall success rate of 68%, which increased to 79% after a median of 25 months' follow-up in ciprofloxacin-susceptible GN-PJIs treated with ciprofloxacin. Ciprofloxacin treatment exhibited an independent protective effect (adjusted hazard ratio (aHR) 0.23; 95% CI, 0.13-0.40; p<0.001), whereas chronic renal impairment predicted failure (aHR, 2.56; 95% CI, 1.14-5.77; p 0.0232). Our results confirm a 79% success rate in ciprofloxacin-susceptible GN-PJI treated with debridement, ciprofloxacin and implant retention. New therapeutic strategies are needed for ciprofloxacin-resistant PJI.

Effect of human natural xenoantibody depletion and complement inactivation on early pig kidney function.

Preformed xenoreactive natural antibodies (XNA) and complement mediate hyperacute xenograft rejection (HXR) in pig-to-human discordant xenotransplantation. In a pig kidney-human blood xenoperfusion model, we investigated whether XNA depletion and/or human complement inactivation preserved early pig kidney function. Pig kidneys were perfused for 180 min with pig blood (AUTO group, n = 8), human blood (HETER group, n = 6), complement-inactivated human blood (COMi group, n = 5), XNA-depleted human blood (ABd group, n = 5) or complement-inactivated and XNA-depleted human blood (ABd&COMi group, n = 5). HETER kidneys were rejected after 15-30 min and showed vascular microthrombi and interstitial hemorrhages. XNA depletion and/or complement inactivation prevented HXR. The glomerular filtration rate in ABd, COMi and ABd&COMi groups was significantly lower than in the AUTO group. Also, beyond 60 min, the COMi group showed a significantly lower glomerular filtration rate than that observed in ABd and ABd&COMi groups. Kidneys from ABd, COMi and ABd&COMi groups displayed endothelial cell edema, as well as higher soluble P-selectin levels and a higher renal myeloperoxidase content than the AUTO group kidneys. COMi and ABd&COMi groups had a significantly lower renal myeloperoxidase level than the HETER group. Also, in contrast to HETER and ABd groups, these complement-inactivated groups failed to show a positive correlation between P-selectin and renal myeloperoxidase. We also investigated platelet-activating factor (PAF) as possible mediator for these functional and pathologic changes. We found that blood PAF levels were similar in HETER, ABd, COMi and ABd&COMi groups and significantly higher than in the AUTO group. Also, when PAF was added to porcine endothelial cell monolayers, morphological changes due to cytoskeleton contraction were observed, and these changes were prevented by preincubation with a PAF receptor antagonist. In conclusion, although depletion of XNA and/or complement inactivation prevent HXR, the pig kidney function is not preserved at the level of the autologous combination. The PAF overproduction observed in the xenogenic combination, which is independent of the presence of XNA and complement, may be, at least in part, responsible for early endothelial cell morphological changes still present when HXR is prevented.

Antimicrobial activity of flavonoids from leaves of Tagetes minuta.

The total extract and fractions with different solvents, obtained from leaves of Tagetes minuta, showed several degrees of antimicrobial activity against Gram positive and Gram negative microorganisms. The same fractions were inactive against Lactobacillus, Zymomonas and Saccharomices species. The major component of the extract: quercetagetin-7-arabinosyl-galactoside, showed significant antimicrobial activity on pathogen microorganisms tested. Correlation results were carried out using chloramphenicol as standard antibiotic.