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This study explored plasma levels and urinary and fecal excretion of metabolites and microbial-derived catabolites over a 24 h period following the ingestion of red wine (RWP) or grape seed (GSP) proanthocyanidin-rich extracts by rats. In total, 35 structurally-related (epi)catechin metabolites (SREMs) and 5-carbon side chain ring fission metabolites (5C-RFMs) (phenyl-γ-valerolactones and phenylvaleric acids), and 50 phenolic acid and aromatic catabolites were detected after intakes of both extracts. The consumption of the RWP extract, but not the GSP extract, led to the appearance of a ∼200 nmol L -1 peak plasma concentration of SREMs formed from flavan-3-ol monomers. In contrast, ingestion of the GSPs, but not the RWPs, resulted in a substantial increase in microbiota-derived 5-carbon side chain ring fission metabolites (5C-RFMs) in plasma. 5C-RFMs, along with low molecular weight phenolic catabolites were detected in urine after ingestion of both extracts. The GSP and RWP extracts had respective mean degrees of polymerisation 5.9 and 6.5 subunits, and the RWP extract had an upper polymer size of 21 subunits compared to 44 subunits for the GSP extract. The differences in plasma metabolite profiles might, therefore, be a consequence of this polydispersity impacting on the microbiota-mediated rates of cleavage of the proanthocyanidin subunits and their subsequent metabolism and absorption. Urinary excretion of phenolic catabolites indicated that 11% of RWPs and 7% for GSPs were subjected to microbial degradation. In all probability these figures, rather than representing the percentage of proanthocyanidins that are completely degraded, indicate partial cleavage of monomer subunits producing a much higher percentage of shortened proanthocyanidin chains. Obtaining more detailed information on the in vivo fate of proanthocyanidins is challenging because of the difficulties in analysing unabsorbed parent proanthocyanidins and their partially degraded flavan-3-ol subunit chains in feces. Further progress awaits the development of improved purification and analytical techniques for proanthocyanidins and their use in feeding studies, and in vitro fecal and bacterial incubations, with radio and/or stable isotope-labelled substrates.

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are a new family of endogenous lipids recently discovered. Several studies reported that some FAHFAs have antidiabetic and anti-inflammatory effects. The objective of this study was to explore the impact of two FAHFAs, 9-PAHPA or 9-OAHPA, on the metabolism of mice. C57Bl/6J male mice, 6 weeks old, were divided into 3 groups of 10 mice each. One group received a control diet and the two others groups received the control diet supplemented with 9-PAHPA or 9-OAHPA for 12 weeks. Mouse weight and body composition were monitored throughout the study. Some days before euthanasia, energy expenditure, glucose tolerance and insulin sensitivity were also determined. After sacrifice, blood and organs were collected for relevant molecular, biochemical and histological analyses. Although high intake of 9-PAHPA or 9-OAHPA increased basal metabolism, it had no direct effect on body weight. Interestingly, the 9-PAHPA or 9-OAHPA intake increased insulin sensitivity but without modifying glucose tolerance. Nevertheless, 9-PAHPA intake induced a loss of glucose-stimulated insulin secretion. Surprisingly, both studied FAHFAs induced hepatic steatosis and fibrosis in some mice, which were more marked with 9-PAHPA. Finally, a slight remodeling of white adipose tissue was also observed with 9-PAHPA intake. In conclusion, the long-term high intake of 9-PAHPA or 9-OAHPA increased basal metabolism and insulin sensitivity in healthy mice. However, this effect, highly likely beneficial in a diabetic state, was accompanied by manifest liver damage in certain mice that should deserve special attention in both healthy and pathological studies., Competing Interests: Conflict of interest The authors confirm that this article content has no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: In our center, until 2018, MRI-targeted biopsy was underused. Since January 2018, we systematically performed MRI-targeted biopsy for suspicious PI-RADS ≥ 3 lesions in accordance to the recent guidelines. We hypothesized that the implementation of systematic prebiopsy MRI would increase the detection rate (DR) of prostate cancer (PCa) without increasing DR of clinically insignificant PCa (insignPCa)., Patients and Methods: A retrospective study including consecutive men who underwent prostate biopsy for suspicion of PCa in our center between January 2017 and December 2018 was conducted. Combined biopsies were performed for suspicious MRI and systematic biopsies for nonsuspicious MRI. The primary outcome was to compare the DR of PCa per year. Secondary outcomes included DRs of clinically significant PCa (csPCa) and insignPCa between both years and outcomes of targeted vs systematic biopsies., Results: A total of 306 men (152 in 2017 and 154 in 2018) were included. Respectively, median (IQR) age was 69 (63-75) vs 70 (65-76) years (p = 0.29) and median (IQR) PSA density was 0.17 (0.13-0.28) vs 0.17 (0.11-0.26) (p = 0.24). There was a significant increase in prebiopsy MRI performed (120 [78.9%] vs 143 [92.8%]; p < 0.001) in 2018. DRs of PCa (94 [61.8%] vs 112 [72.7%]; p = 0.04) and csPCa (76 [50%] vs 95 [61.6%]; p = 0.04) increased in 2018, while the insignPCa DR was stable (p = 0.13). The DR of PCa was 58.3%, 65% and 71.2%, respectively, in targeted, systematic and combined biopsies (p = 0.02). In case of nonsuspicious MRI, the prevalence of csPCA was 12.5%., Conclusions: Introducing systematical MRI-targeted biopsy in our clinical setting increased the PCa DR without overdiagnosing insignPCa. Implementation of prebiopsy MRI does not seem to avoid the need for systematic biopsy, and nonsuspicious MRI should not obviate the need for prostate biopsy when otherwise clinically indicated.

Purpose: There have recent reports in the literature of increased rates of bladder recurrence (BR) after radical nephroureterectomy (RNU) when diagnostic flexible ureteroscopy (DFU) was performed before RNU. The technical heterogeneity of DFU was a major bias in these studies. Our purpose was to evaluate the impact of a standardized DFU technique before RNU on the risk of BR., Methods: A retrospective monocenter study including patients who underwent RNU for upper tract urothelial carcinoma (UTUC) between 2005 and 2017. 171 patients were identified. 78 patients were excluded owing to a history of bladder cancer before RNU or neo-adjuvant/adjuvant chemotherapy. 93 included patients were stratified according to pre-RNU ureteroscopy (DFU + 70 patients) or no pre-RNU ureteroscopy (DFU-23 patients). The standardized DFU technique consisted of systematic ureteral sheath (ch9-10), flexible ureteroscopy, biopsy, and drainage with a mono-J/bladder catheter to avoid contact of contaminated urine of the upper tract with the bladder., Results: Epidemiological, initial staging, and postoperative tumoral characteristics were similar in both groups. Mean follow-up was 35 months [2-166], 47(50%) BR occurred with 41(87%) in the DFU + group, and pre-RNU-DFU was an independent predictive factor of BR (OR = 4[1.4-11.9], P = 0.01) (Cox regression model). The characteristics of BR were similar in both groups, although BR occurred earlier in DFU + (427 days vs. 226 days (P = 0.07))., Conclusion: Bladder recurrence after diagnostic ureteroscopy + nephroureterectomy was high despite technical precautions to avoid contact of bladder mucosa with contaminated urine from the upper urinary tract. Post-DFU endovesical instillation should be investigated.

Purpose: Palm (PO) and olive oils (OO) are the two most consumed and/or used oils in the world for food elaboration. These oils should not be confused with the solid palm stearin which is widely used in pastry making. Large number of studies was reported dealing with adverse/beneficial cardiovascular effects of PO and OO, whereas few studies were conducted to compare their potential effects on hepatic steatosis and liver lipid metabolism. The aim of this study was to compare the metabolic effects of high intake of POs (both crude and refined) and virgin OO on surrogate parameters of glucose tolerance, hepatic lipid metabolism and liver integrity., Methods: Thirty-two young male Wistar rats were divided into four equal groups and fed either control diet (11% energy from fat) or three high-fat diets rich in crude or refined POs or in OO (56% energy from fat), during 12 weeks. Systemic blood and liver biochemical parameters linked to glucose and lipid metabolism as well as hepatic steatosis and liver fatty acid composition were explored. The inflammation and oxidative stress status as well as the expression of several genes/proteins were also analyzed., Results: The major effects of POs intake concerned glucose metabolism and liver fatty acid composition, whereas the major effects of OO intake concerned hepatic TG accumulation, inflammation, and cytolysis., Conclusions: In conclusion, high dietary intake of PO compromises glucose tolerance whereas high dietary intake of OO compromises hepatic lipid composition and liver integrity. However, adverse hepatic effects of OO observed in this study may not be transposed to human since, (a) the rodent model could lead to different effects than those observed in humans and (b) the average normal OO amounts ingested in the population are lower than those corresponding to a high-fat diet. So, further studies are needed to determine a maximum non-invasive dietary intake of OO.

Objectives: To describe a new technique for robot-assisted AMS-800 artificial urinary sphincter (AUS) bladder neck implantation in women., Patients and Methods: We reviewed the medical files of patients who underwent robot-assisted AUS implantation between March 2017 and November 2018 at our centre. All of the implantations were performed using a posterior approach to the bladder neck in order to avoid blind dissection and the risk of vaginal and/or bladder injury. This strategy was viewed as an alternative to the anterior robot-assisted implantation recently described. The AUSs were activated 5 weeks after implantation. Patients were followed up at 3, 6 and 12 months, then annually., Results: Eight patients, with a median age of 64 years, underwent robot-assisted AUS implantation via a posterior approach to the bladder neck. The median preoperative pad weight was 300 g/24 h. The median operating time was 244 min. No peri-operative vaginal and or bladder injuries were observed. At a median of 12 months of follow-up, all the AUSs were functional. Five patients required no protection (62.5%), three had day protection (37.5%), and all said they were satisfied except for one patient (12.5%) who requested treatment for persistent urge incontinence., Conclusion: Robot-assisted AUS implantation in women via a posterior approach to the bladder neck is a procedure that is simple, reproducible and safe. The short-term functional results are satisfactory and comparable to those obtained via an open approach. A more long-term comparison of the efficacy and longevity of AUSs implanted using this posterior approach is needed to confirm its benefit compared with the anterior robot-assisted approach and the classic open technique., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Purpose: Reusable flexible-ureteroscopes (fURS) require personnel and budget for processing and repairing, whereas single-use fURS were recently developed. After exclusive reusable fURS since 2011, we experienced high repair costs and single-use fURS were therefore introduced in mid-2017. We aimed to evaluate economic and practical advantages and disadvantages of reusable versus single-use fURS., Materials and Methods: First, we evaluated the incidence of breakage and repairs of reusable fURS in 2017. We assessed the overall operational costs of reusable fURS including purchase, processing, and repairing in our institution from 2011 to 2017. Following our experience, we created a model to compare operation costs/procedure of single-use fURS with reusable fURS depending on repair costs., Results: In 2017, repair costs of reusable fURS increased by 345% compared with the period 2011-2016, causing: a median unavailability per reusable fURS of 200 days/year (100-249), median number of functioning fURS 0/5-3/5 per operating day, while unavailability of reusable fURS had become the first reason for cancellation of procedure. Since it was introduced, single-use fURS accounted for 59% of the flexible ureteroscopy activity. Taking into account the costs of processing, maintenance and repair, in 2011-2016 versus 2017, the single-use fURS was cost-effective compared with the reusable fURS until the 22nd procedure versus the 73rd procedure, respectively., Conclusions: After years of exclusive reusable fURS, the rising incidence of breakage not only increased maintenance costs but also hampered daily activity owing to unavailability of the devices. The introduction of single-use with reusable fURS provided substantial help to maintain our activity.

The use of Spirulina platensis (Sp) as a functional food was suggested decades ago. Biological incorporation of Silicon (Si) into Sp increases its bioavailability for potential food supplement applications. This work aimed at determining the effects of Sp and Si-enriched Sp (Sp+Si) on metabolic syndrome features in Zucker fatty rats. Thirty Zucker fatty rats were divided into three groups and supplemented with placebo or Sp or Sp+Si croquettes for 12 weeks. Food consumption, glucose intolerance, hepatic steatosis, and mitochondrial and oxidative stress were determined. Zucker fatty rats exhibited several hepatic metabolic alterations as well as mitochondrial and oxidative stress perturbations. The intake of Sp increased plasma TG levels and decreased the hepatic NADPH oxidase activity and ameliorated transitorily the glucose intolerance. However, Si-spirulina does not appear to have more beneficial effects than spirulina alone. Other experiments with different species of rats/mice, different diets, or durations of diet intake should be undertaken to confirm or infirm these results. PRACTICAL APPLICATIONS: Glucose intolerance and hepatic steatosis, two major components of metabolic syndrome, are increasing and becomes a major public health issue. Use of Spirulina platensis (Sp) as a functional food was suggested as a protein-dense food source. Bioavailable silicon (Si) may be an essential nutrient for higher animals, including humans. Sp but not Sp+Si decreased liver NADPH oxidase activity and improved transitorily glucose tolerance. This is the first study where Sp and Sp+Si effect on glucose intolerance is reported in Zucker rat. Other experiments should be undertaken to confirm or infirm invalidate the beneficial effects of Sp+Si supplement in the metabolic syndrome features., (© 2019 Wiley Periodicals, Inc.)

Objective: To evaluate the clinical efficacy, urodynamic effect and safety of Botulinum Toxin A (BTXA) injections after failure of augmentation enterocystoplasty (AE) performed for neurogenic detrusor overactivity., Patients and Methods: We performed a multicenter retrospective study that included patients who had AE and at least one injection of BTXA after AE in 15 GENULF (French Speaking Neuro-Urology Study Group) centers. Clinical and urodynamic data were collected from medical files according to a standardized questionnaire and colligated in an anonymous database., Results: Thirty-three patients with an injection of BTXA after AC in 9 out of 15 centers were included. Mean age at the time of AE was 24 ± 15 years. Overall efficacy (defined by clinical efficacy associated with a request by the patient for reinjection) was observed in 58% of the patients. Mean maximum cystomanometric capacity increased by 28% (333 ± 145 vs 426 ± 131 mL; P = .007) and maximum detrusor pressure (P d et max ) decreased by 43% (44 ± 37 vs 25 ± 18 cm H 2 O; P = .02) after BTXA. Only one side effect was recorded out of the 152 procedures (transient generalized muscle weakness without respiratory distress)., Conclusion: In patients with failure after AE performed for neurogenic detrusor overactivity, injection of BTXA in the enlarged bladder was effective in over half of the cases with low morbidity. If this therapeutic approach were confirmed, it could be proposed as an alternative to AE surgical revision., (Copyright © 2019. Published by Elsevier Inc.)

Objective: The objective of our study was to evaluate, in a review of the literature, the impact of diagnostic ureteroscopy before total nephroureterectomy (NUT) on the risk of bladder recurrence., Methods: We conducted a literature review in the Pubmed database in March 2018. Initial research identified 45 publications. Following full text screening, 9 studies were finally included, with a total of 1041 NUT with URS prior versus 2909 NUT alone. The primary endpoint was bladder recurrence. Secondary objectives were specific survival and overall survival., Results: Bladder recurrence was reported in the 9 studies included. Diagnostic ureteroscopy was significantly associated with an increased risk of post-NUT bladder recurrence (HZ 1.42 [1.29-1.56], P<0.01). The specific survival and overall survival at 5 years, were reported in respectively 4 and 2 studies. There was no impact of the pre-NUT diagnostic URS on the specific survival (HZ 0.75 [0.54-1.03], P=0.08) or post-NUT overall survival (HZ 1.15 [0.68-1.96], P=0.59)., Conclusion: The URS diagnostic before NUT for TVEUS is associated with a significant increase in the risk of postoperative bladder recurrence., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Metabolic syndrome components, including obesity, dyslipidemia and impaired glucose homeostasis, become a major public health issue. Muscles play a predominant role in insulin-mediated glucose uptake, and high fat diets may negatively affect muscle function and homeostasis. This work aimed to study the time-course of muscle lipid accumulation, oxidative stress and mitochondrial dysfunction and their association to impaired glucose homeostasis in rats fed an obesogenic diet. Male Wistar rats were fed with a standard or a high fat/high fructose (HFHFr) diet and sacrificed on 4, 8, 12, 16, 20 weeks. Rats fed the HFHFr diet developed mild overweight, increased liver and adipose tissue weights and glucose intolerance. The impaired glucose homeostasis increased gradually with the HFHFr diet to become significant on the 12th and 16th weeks of diet. In parallel, the muscle lipid composition showed an increase in the saturated fatty acids and the monounsaturated fatty acids with a marked decrease in the polyunsaturated fatty acids. The HFHFr diet also increased muscle contents of both diacylglycerols and Ceramides. Surprisingly, HFHFr diet did not induce major muscle mitochondrial dysfunction or oxidative stress. These results indicate that muscle lipid alterations, as well as impaired glucose homeostasis occur as early as the 8th week of HFHFr diet, increase to reach a plateau around the 12th-16th weeks of diet, and then attenuate towards the end of study. At these diet treatment durations, muscle mitochondrial activity and oxidative stress remained unchanged and do not seem to have a major role in the observed impaired glucose homeostasis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Inflammation and oxidative stress are thought to be involved in, or associated with, the development of obesity, dyslipidemia, hepatic steatosis, and insulin resistance. This work was designed to determine the evolution of inflammation and oxidative stress during onset and progression of hepatic steatosis and glucose intolerance. Seventy-five male Wistar rats were divided to control and high-fat high-fructose (HFHFr) groups. A subgroup of each group was sacrificed at 4, 8, 12, 16, and 20 weeks. HFHFr-fed rats exhibited overweight, glucose intolerance, and hepatic steatosis with increased contents of hepatic diacylglycerols and ceramides. The HFHFr diet increased hepatic interleukin 6 (IL-6) protein and adipose tissue CCL5 gene expression and hepatic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity but not mitochondrial reactive oxygen species (ROS) production. The HFHFr diet decreased plasma and liver levels of isoprostanoid metabolites as well as plasma thiobarbituric acid-reactive substance (TBARS) levels. Hepatic glutathione content was decreased with a moderate decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) with the HFHFr diet. Overall, HFHFr diet led to hepatic lipid accumulation and glucose intolerance, which were accompanied by only moderate inflammation and oxidative stress. Most of these changes occurred at the same time and as early as 8 or 12 weeks of diet treatment. This implies that oxidative stress may be the result, not the cause, of these metabolic alterations, and suggests that marked hepatic oxidative stress should probably occur at the end of the steatotic stage to result in frank insulin resistance and steatohepatitis. These findings need to be further evaluated in other animal species as well as in human studies., (© 2019 AOCS.)

The prevalence of metabolic syndrome components, such as obesity, glucose intolerance and hepatic steatosis, is rapidly increasing and becoming a major issue of public health. The present work was designed to determine the effects of Spirulina platensis (Sp) algae and silicon-enriched Sp on major metabolic syndrome components in obesogenic diet-fed rats. Forty male Wistar rats were divided into 4 groups. Ten rats were fed a control diet and 30 rats were fed a high fat (HF) diet. The HF groups were divided into three groups and supplemented with placebo or Sp or Si-enriched Sp for 12 weeks. Dietary intake and body weight were recorded. Oral glucose tolerance test and surrogate metabolic syndrome (insulin, leptin, adiponectin and lipids), mitochondrial function (enzymatic activity of respiratory chain complexes and β-hydroxyacyl-CoA dehydrogenase), NADPH oxidase activity and several long-established oxidative stress markers were measured in the blood and liver. The HF diet induced obesity, glucose intolerance, hepatic steatosis and huge metabolic alterations, associated with higher NADPH oxidase activity and lower hepatic sulfhydryl group and glutathione contents. Otherwise, the Sp and Sp + Si supplements showed some interesting effects on rat characteristics and particularly on blood and hepatic metabolic parameters. Indeed, the intake of Sp or Sp + Si mainly improved glucose tolerance and decreased the enzymatic activity of hepatic NADPH oxidase. Overall, Si supplementation of spirulina does not appear to have more beneficial effects than spirulina alone. Other experiments with different species of rats/mice, different diets or different durations of diet intake should be undertaken to confirm or invalidate these results.

The development of nutraceutical ingredients has risen as a nutritional solution for health prevention. This study evaluated the effects of Oleactiv ® , an ingredient developed for the prevention of atherogenesis, in hypercholesterolemic hamsters. Oleactiv ® is a polyphenol-rich ingredient obtained from artichoke, olive and grape extracts as part of fruit and vegetables commonly consumed within the Mediterranean diet. A total of 21 Golden Syrian hamsters were divided into three groups. The standard group (STD) was fed a normolipidemic diet for 12 weeks, while the control group (CTRL) and Oleactiv ® goup (OLE) were fed a high-fat diet. After sacrifice, the aortic fatty streak area (AFSA), plasmatic total cholesterol (TC), high-density lipoproteins (HDL-C), non-HDL-C and triglycerides (TG), were assessed. The cholesterol efflux capacity (CEC) of hamster plasma was quantified using a radiolabeled technique in murine macrophages J774. OLE administration induced a significant reduction of AFSA (-69%, p < 0.0001). Hamsters of the OLE group showed a significant decrease of both non-HDL-C (-173 mmol/L, p < 0.05) and TG (-154 mmol/L, p < 0.05). Interestingly, OLE induced a significant increase of total CEC (+17,33%, p < 0,05). Oleactiv ® supplementation prevented atheroma development and had positive effects on the lipid profile of hypercholesterolemic hamsters. The increased CEC underlines the anti-atherosclerotic mechanism at the root of the atheroma reduction observed.

This study developed, optimized and validated an ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) method to identify and quantify metabolites and microbial-derived catabolites in urine, plasma and feces of rats following ingestion of 50 mg of a red wine proanthocyanidin-rich extract. The method was validated for specificity, linearity, limit of detection (LD) and quantification (LQ), intra-day and inter-day precision, recovery and matrix effects, which were determined for 34 compounds in the three biological matrices. After method validation, three parent flavan-3-ols, four 5-carbon side chain ring fission metabolites, and 27 phenolic acid and aromatic catabolites were quantified in plasma, urine and feces after red wine proanthocyanidin intake. These results establish the value of the UHPLC-HRMS protocol in obtaining a detailed picture of proanthocyanidin metabolites and their microbial-derived catabolites, along with their phase II metabolites, in biological fluids of rat, and potentially in human clinical studies designed to evaluate the bioavailability of dietary flavan-3-ols., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The incidence of obesity and its metabolic complications are rapidly increasing and become a major public health issue. This trend is associated with an increase in the prevalence of non-alcoholic fatty liver disease (NAFLD), insulin resistance and diabetes. The sequence of events leading to NAFLD progression and mitochondrial dysfunction and their interrelation remains to be elucidated. This study aimed to explore the installation and progression of NAFLD and its association with the liver mitochondrial structure and activity changes in rats fed an obesogenic diet up to 20 weeks. Male Wistar rats were fed either a standard or high-fat-high-fructose (HFHFR) diet and killed on 4, 8, 12, 16 and 20 weeks of diet intake. Rats fed the HFHFR diet developed mildly overweight, associated with increased adipose tissue weight, hepatic steatosis, hyperglycaemia and hyperinsulinaemia after 8 weeks of HFHFR diet. Hepatic steatosis and many biochemical modifications plateaued at 8-12 weeks of HFHFR diet with slight amelioration afterwards. Interestingly, several biochemical and physiological parameters of mitochondrial function, as well as its phospholipid composition, in particular cardiolipin content, were tightly related to hepatic steatosis installation. These results showed once again the interrelation between hepatic steatosis development and mitochondrial activity alterations without being able to say whether the mitochondrial alterations preceded or followed the installation/progression of hepatic steatosis. Because both hepatic steatosis and mitochondrial alterations occurred as early as 4 weeks of diet, future studies should consider these four 1st weeks to reveal the exact interconnection between these major consequences of obesogenic diet intake.

Aims: To assess the outcomes of switching to a different brand of botulinum toxin A (BTA, from Botox® to Dysport®) in case of failure of intradetrusor injections (IDI) of Botox® in the treatment of neurogenic detrusor overactivity (NDO)., Methods: The charts of all patients who underwent a switch to IDI of Dysport® after failure of an IDI of Botox® at six departments of neurourology were retrospectively reviewed. The main outcomes of interest were the bladder diary data and four urodynamic parameters: maximum cystometric capacity (MCC), maximum detrusor pressure (PDET max), and volume at first uninhibited detrusor contraction (UDC)., Results: Fifty-seven patients were included. After the first injection of Dysport®, no adverse events were reported. A significant decrease in number of urinary incontinence episodes per day was observed in 52.63% of patients (P < 0.001) and all patients experienced a reduction in PDET Max (-8.1 cmH20 on average; P = 0.003). MCC significantly increased by a mean of 41.2 (P = 0.02). The proportion of patients with no UDC increased significantly at week 6 after ATA injections (from 15.79% to 43.9%; P = 0.0002). Hence, 32 patients draw clinical and/or urodynamic benefits from the botulinum toxin switch from (56.14%). After a median follow up of 21 months, 87% of responders to BTA switch were still treated successfully with BTA., Conclusion: Most patients refractory to Botox® (56.14%) draw benefits from the switch to Dysport®., (© 2017 Wiley Periodicals, Inc.)

High-intensity exercises are known to provoke delayed onset muscle soreness (DOMS). Delayed onset muscle soreness typically occurs within the first 24 h, peaks between 24 and 72 h, and can last as long as 5-7 days post-exercise. Delayed onset muscle soreness is a multifactorial process involving both mechanical and biochemical components, associated with clinical features that may limit range of motion, and athletes seek for effective recovery strategies to optimize future training sessions. TensLess ® is a food supplement developed to help manage post-exercise recovery. The supplement has been investigated on 13 recreationally active athletes of both sex, during a randomized, double-blind, and crossover clinical investigation, including a 3-week washout period. The clinical investigation was based on the study of TensLess ® effects for DOMS management and on the reduction of associated muscle damages following an eccentric exercise protocol. Supplementation with TensLess ® induced significant decrease in DOMS perception (-33%; p = 0.008) as of the first 24 h; this was significantly correlated with a lowered release of muscle damage-associated biomarkers, namely myoglobin, creatinine, and creatine kinase, for the whole length of the recovery period. Taken together, these positive results clearly indicate that post-exercise supplementation with TensLess ® may preserve myocytes and reduce soreness following eccentric exercise-induced damages, and, accordingly, significantly shorten muscle recovery. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Workout capacity is energy-production driven. To produce peak metabolic power outputs, the organism predominantly relies more on anaerobic metabolism, but this undoubtedly has a negative and limiting impact on muscle function and performance. The aim of the study was to evaluate if an innovative polyphenol-based food supplement, PerfLoad ® , was able to improve metabolic homeostasis and physical performance during high-intensity exercises under anaerobic conditions. The effect of a supplementation has been investigated on fifteen recreationally-active male athletes during a randomized, double-blind and crossover clinical investigation. The Wingate test, an inducer of an unbalanced metabolism associated to oxidative stress, was used to assess maximum anaerobic power during a high-intensity exercise on a cycle ergometer. Supplementation with PerfLoad ® correlated with a significant increase in total power output (5%), maximal peak power output (3.7%), and average power developed (5%), without inducing more fatigue or greater heart rate. Instead, oxidative homeostasis was stabilized in supplemented subjects. Such results demonstrated that PerfLoad ® is a natural and efficient solution capable of, similarly to training benefits, helping athletes to improve their physical performance, while balancing their metabolism and reducing exercise-induced oxidative stress.

Objective: The aim of this study was to investigate the effects of dietary silicon-enriched spirulina (SES) on atherosclerosis., Methods: Hamsters (six per group) on a high-fat (HF) diet received SES or non-enriched spirulina (both at 57 mg/kg body weight) daily. This corresponded to 0.57 mg silicon/kg body weight daily., Results: The HF diet induced dyslipidemia, insulin resistance, oxidative stress, and vascular dysfunction. Compared with the HF group, SES attenuated increases of lipemia and prevented insulin resistance (IR) (P = 0.001). SES protected against oxidative stress through a reduction of heart (P = 0.006) and liver (P < 0.0001) nicotinamide adenine dinucleotide phosphate-oxidase activity and by sparing the activity of superoxide dismutase (P = 0.0017) and glutathione peroxidase (P = 0.01861). SES decreased inflammation, lowering tumor necrosis factor-α (P = 0.0006) and interleukin-6 levels (P = 0.0112), decreasing polymorphonuclear cells and preventing nuclear factor-κB activity (P = 0.0259). SES corrected plasma level of monocyte chemoattractant protein-1 (P = 0.0380), which was increased by the HF diet. Finally, SES supplementation prevented vascular and endothelial functions assessed respectively by the contractile response to the agonist phenylephrine and the relaxation induced by acetylcholine., Conclusion: SES protects against metabolic imbalance, inflammation, oxidative stress, and vascular dysfunction induced by an HF diet, and could prevent the atherogenic processes. Synergistic effects between spirulina and silicon were observed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Silicon has beneficial effects especially on bones and skin and is important in cardiovascular pathophysiology. Furthermore, in spontaneously hypertensive rats, it reduces hypertension and increases antihypertensive and antiatherogenic gene expressions in the aorta. Thus, incorporating silicon into spirulina could be a way to produce a bioavailable food supplement. The potential toxic effects of silicon-rich spirulina (SES) through haematological and biochemical parameters and inflammatory and oxidative status were evaluated in rats' blood and liver tissue. The study consisted in a 90-day experiment on female and male rats supplemented with three doses (28.5, 57 and 285 mg/kg BW/day) of SES. No mortality, abnormal clinical signs, behavioural changes or macroscopic findings were observed whatever the groups. Haematological parameters were not modified in SES treated-groups. No marked change was recorded in biochemical parameters The liver endogenous antioxidant enzymes (SOD, GPx, catalase) activities were not modified whatever the gender and the dose, just as markers of oxidative stress (O2°(-), TBARS, thiols) and inflammation such as IL-6 and TNF-alpha. Our findings indicate that dietary supplementation of silicon-rich spirulina on rats has no harmful side nor toxic effects and could be beneficial especially in the case of suspicion or installation of pathologies due to oxidative stress., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Because of their antimicrobial properties, the use of silver nanoparticles (AgNPs) is increasing fast in industry, food, and medicine. In the food industry, nanoparticles are used in packaging to enable better conservation products such as sensors to track their lifetime, and as food additives, such as anti-caking agents and clarifying agents for fruit juices. Nanoemulsions, used to encapsulate, protect and deliver additives are also actively developed. Nanomaterials in foods will be ingested and passed through the digestive tract. Those incorporated in food packaging may also be released unintentionally into food, ending up in the gastrointestinal tract. It is therefore important to make a risk assessment of nanomaterials to the consumer. Thus, exposure to AgNPs is increasing in quantity and it is imperative to know their adverse effects in man. However, controversies still remain with respect to their toxic effects and their mechanisms. Understanding the toxic effects and the interactions of AgNPs with biological systems is necessary to handle these nanoparticles and their use. They usually generate reactive oxygen species resulting in increased pro-inflammatory reactions and oxidative stress via intracellular signalling pathways. Here, we mainly focus on the routes of exposure of AgNPs, toxic effects and the mechanisms underlying the induced toxicity., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: We evaluated the success of endoscopic treatment of symptomatic vesicoureteral reflux after renal transplantation and identified factors predicting success., Materials and Methods: Endoscopy was performed for symptomatic vesicoureteral reflux after renal transplantation in 38 women and 20 men between January 2000 and December 2010. Reflux was documented by retrograde cystography and its symptomatic character was determined by at least 1 episode of acute graft pyelonephritis. The results of endoscopic treatment were evaluated clinically at 1 and 3 months, and annually, and by cystography at 3 months. Clinical success was defined as absent acute graft pyelonephritis during followup. Radiological success was defined as absent reflux on followup cystography at 3 months., Results: Endoscopic treatment was clinically successful in 32 patients (56.1%), including 26 (65%) who received dextranomer-hyaluronic acid and 5 (33.3%) who received polydimethylsiloxane. Treatment was radiologically successful in 14 patients (26.4%) at a mean ± SD followup of 38 ± 33 months. On multivariate analysis male gender and dextranomer-hyaluronic acid were factors predictive of clinical success. Reflux grade did not predict success or failure. No high grade complication was reported., Conclusions: Endoscopic treatment of symptomatic vesicoureteral reflux of a transplanted kidney was effective in half of the cases regardless of the bulking agent used. However, dextranomer-hyaluronic acid appeared to be more effective than polydimethylsiloxane. Due to its minimally invasive nature and low morbidity endoscopic treatment with dextranomer-hyaluronic acid could be proposed as preoperative first line treatment for symptomatic vesicoureteral reflux of a transplanted kidney regardless of reflux grade., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

A comprehensive study of the bioavailability of orally administered silver nanoparticles (AgNPs) was carried out using a rat model. The silver uptake was monitored in liver and kidney tissues, as well as in urine and in feces. Significant accumulation of silver was found in both organs, the liver being the principal target of AgNPs. A significant (∼50%) fraction of silver was found in feces whereas the fraction excreted via urine was negligible (< 0.01%). Intact silver nanoparticles were found in feces by asymmetric flow field-flow fractionation (AsFlFFF) coupled with UV-Vis analysis. Laser ablation-ICP MS imaging showed that AgNPs were able to penetrate into the liver, in contrast to kidneys where they were retained in the cortex. Silver speciation analysis in cytosols from kidneys showed the metallothionein complex as the major species whereas in the liver the majority of silver was bound to high-molecular (70-25 kDa) proteins. These findings demonstrate the presence of Ag(i), released by the oxidation of AgNPs in the biological environment.

Objective: To report efficacy and morbidity of periurethral adjustable balloons (PUAB) in the treatment of stress urinary incontinence (SUI) with intrinsic sphincter deficiency (ISD)., Patients and Methods: Retrospective descriptive and analytic patients cohort study was performed from July 2010 to June 2012. We reviewed data from 43 patients (19 women and 24 men). The patients were categorized into 3 groups: i) women, ii) men after prostatectomy, iii) men with neurogenic SUI (prostate in position). Sandvick score and the average of 3 days 24 h Pad test evaluated the efficacy of the device. The patients impression of improvement was assessed in three degrees: completely improved, partially improved, not improved., Results: After a median follow-up of 67 weeks (min. 40, max. 91) a significant improvement of the score of Sandvik was observed (8 to 4, P<0.005). The proportion of dry patients or with one security protection in the three groups was 57.9%, 64.3% and 50% respectively for women, men after prostatectomy, and men with neurological SUI. About 27.9% (12/43) of the patients had post-operative complications. These complications required an explantation of the PUAB in 11/12 patients among whom 7/11 (63.6%) had a delayed re-implantation of the device., Conclusion: In this series, the overall efficacy observed was 67.4% with a post-operative complication rate of 27.9%. The device adjustment was done in consultation as well as the complications management and the explantation when necessary., Level of Evidence: 4., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

β,β-Carotene 15-15' mono-oxygenase 1 (BCMO1) is a key enzyme in vitamin A (VitA) metabolism in mammals. Dietary compounds, such as carotenoids and polyphenols, were reported to influence BCMO1 activity. The aim of this study was to evaluate the effect of hesperidin (Hes), on the VitA bioefficacy of β-carotene (Bc) from orange-fleshed sweet potato, using Mongolian gerbils, focussing on BCMO1 activity. Gerbils (n=50) depleted in VitA were divided into five groups fed with basal diet containing 3% white- or orange-fleshed sweet potatoes supplemented or not with Hes. Liver BCMO1 activity was low, with no significant differences between groups. Interestingly, intestinal mucosal BCMO1 activity was significantly higher in the gerbils fed without Bc or VitA than those fed with a VitA/Bc-supplemented diet. Finally, our results show that, under a low VitA status, Hes dramatically stimulated intestinal BCMO1 activity, an effect that could possibly be related to its action as an agonist of PPARγ., (Copyright © 2014. Published by Elsevier Ltd.)

Scope: High-fat (HF) diets contribute to the development of cardiovascular diseases and the metabolic syndrome. This study was undertaken to investigate the beneficial effects of Vineatrol®-enriched red wines on blood lipids, oxidative stress and inflammation, and the role of some metabolic pathway regulatory proteins., Methods and Results: Golden Syrian hamsters received an HF diet for 13 wk, in the presence or absence of red wines supplemented with Vineatrol® (RWV) or not. The HF diet increased plasma cholesterol, triglycerides, glucose, and insulin, which were attenuated by RWV treatment. RWV protected against the HF-induced increase in liver nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and spared antioxidant enzyme activities. RWV did not reduce either liver steatosis or increased plasma leptin due to the HF diet, but greatly improved adiponectinemia. In the liver, RWV affected the inflammatory response by decreasing polymorphonuclear cell number and lowering TNF-α and IL-6 levels. Moreover, the increase in NF-κB activity in the HF group liver was prevented by RWV. Finally, RWV partially corrected low SIRT1 levels due to the HF diet but had no influence on SIRT3 or p-AMPK protein levels., Conclusion: Our studies suggest that RWV is capable of reversing the atherogenic process induced by an HF diet in hamster tissues., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Oxidative stress is involved in obesity. However, dietary antioxidants could prevent oxidative stress-induced damage. We have previously shown the preventive effects of a melon superoxide dismutase (SODB) on oxidative stress. However, the mechanism of action of SODB is still unknown. Here, we evaluated the effects of a 1-month curative supplementation with SODB on the liver of obese hamsters. Golden Syrian hamsters received either a standard diet or a cafeteria diet composed of high-fat, high-sugar, and high-salt supermarket products, for 15 weeks. This diet resulted in insulin resistance and in increased oxidative stress in the liver. However, inflammatory markers (IL-6, TNF-α, and NF-κB) were not enhanced and no liver steatosis was detected, although these are usually described in obesity-induced insulin resistance models. After the 1-month supplementation with SODB, body weight and insulin resistance induced by the cafeteria diet were reduced and hepatic oxidative stress was corrected. This could be due to the increased expression of the liver antioxidant defense proteins (manganese and copper/zinc superoxide dismutase, catalase, and glutathione peroxidase). Even though no inflammation was detected in the obese hamsters, inflammatory markers were decreased after SODB supplementation, probably through the reduction of oxidative stress. These findings suggest for the first time that SODB could exert its antioxidant properties by inducing the endogenous antioxidant defense. The mechanisms underlying this induction need to be further investigated., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: To identify and describe functional urinary symptoms, uro-nephrological complications and their impact on quality of life in a cohort of patients diagnosed with the Wolfram syndrome (SW)., Patients and Methods: A transversal descriptive patient's cohort study was performed. The Urinary Symptom Profile (USP) and the International Consultation Incontinence Questionnaire - Female Lower Urinary Tracts Symptoms (ICIQ-FLUTS) were used to evaluate urinary symptoms and their impact on quality of life through direct interviews conducted by telephone. A less than 6-month old renal ultrasound and serum creatinine results were asked to the patient or physician., Results: Thirty-three patients have been contacted and 22 (73%) agreed to participate in this study. Eighteen patients over 22 had spontaneous micturition when four of them had an urinary diversion (two definitive, two temporaries) before being included in this study. Seventy-three percent of patients with spontaneous micturition had urinary symptoms. A severe or moderate symptoms score was noted in 67% (12/18 patients) and 11% (2/18 patients) respectively., Conclusion: Functional urinary dysfunctions were frequent and impacted quality of life in more than one half of patients diagnosed with SW in this study. Early diagnostic and regular urological follow-up can improve the quality of life and prevent severe urinary complications., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Purpose: To assess both economical and organizational impact as well as bacteriologic safety of a flexible cystoscope with sterile disposable sheath (FCSDS) compared to standard flexible cystoscopy (SFC) in two French urologic academic units., Patients: Two-center prospective study, comparing the use of the FCSDS to the SFC on two consecutive periods of time. Two hundred and five patients were included and divided into each group. Duration procedures and costs were analysed in the two techniques. The urinary tract infection rate was also described. A dedicated sheaths leaks test after use was performed systematically., Results: The preparation time of the fibroscope was longer for the sheathed cystoscopy group: 16.2 minutes versus 10.9 minutes for the standard group. The mean duration of disinfection was significantly shorter for the sheathed cystoscopy group: 53.8 minutes saved compared to the standard group; 99.01% of the tested sheaths, after their use, had no breaches. Urinary tract infections rate were similar in the two groups. The average cost of a sheathed cystoscopy compared to the standard was significantly cheaper in Lyon and almost equivalent in Marseille., Conclusion: The FCSDS allows significant saving over the disinfection duration, consumable costs and staff costs, while ensuring patient bacteriologic safety similar to SFC., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Objectives: The aim of this study was to assess the outcomes of nitinol permanent urethral stents used in detrusor-striated sphincter dyssynergia (DSD) treatment on male patients with a spinal cord injury., Materials: We investigated retrospectively all patients treated from 2004 to 2012. A total of 22 patients were included, with an age ranging from 22 to 76 years old. The DSD syndrome was due to spinal cord injury (18) or various spinal cord diseases (four) and treated with a nitinol urethral stent (11 Ultraflex(®) and 11 Mémotherm(®)). Every patient had an urodynamical study. The follow-up reached at least 2 years., Results: The mean follow-up was 56 months (± 14). Complementary procedures after stenting included: five stent prolongation or displacement (mean interval 7.6 months), six bladder neck incisions (12.2 months), three urethrotomy (42 months), ten obstruction treated by laser (47.3 months). Eight patients had a change of their urinary pattern: four underwent ileal conduit diversion, one had a continent urinary diversion, one chose self intermittent catheterization, two were under indwelling catheterization waiting for another treatment. Stent retrieval was either harmful or impossible for four of them. Three patients were free of complementary procedures., Conclusions: Nitinol urethral stent was an effective treatment initially. However, by the third year, urethral stenosis and hypertrophic growth of the urethral mucosa usually require iterative endoscopic procedures (0.31 per patient per year). Patients treated with permanent uretral stent deserve a yearly endoscopic follow-up. Safety and effectiveness of permanent uretral stent compared to surgical sphincterotomy to treat DSD are discussed., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Objective: To analyze the learning curve of bilateral anterior sacrospinous ligament suspension associated with anterior mesh repair in a single center., Study Design: The first 113 bilateral anterior sacrospinous ligament suspensions associated with anterior mesh repair performed by three surgeons trained together in a single center were analyzed retrospectively for pre-operative, operative and post-operative data. To discover a turning point, all major complications were reported and the study population was divided into five groups of approximatively 22 interventions each, classed chronologically. Statistical analysis was carried out by the Cochran-Armitage trend test and Cox proportional hazards models. Other descriptive statistics were computed with the use of standard methods for means and proportions., Results: Of the 103 evaluable patients (91.2%), the success rate for both anterior and apical compartments was 87.4%. The rate of major post-operative complications was 7.2% (8/111). Statistical analysis showed that the risk of major complications was reduced by approximately 30% every ten procedures (HR=0.71, 95% CI: 0.53-0.95). Success rate, operative time and hospital stay remained unchanged throughout the series. Mesh exposure rate was 3.6%., Conclusion: Bilateral anterior sacrospinous ligament suspension associated with anterior mesh repair was associated with a learning curve to decrease the rate of major complications., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

We evaluated the effect of the intake of a grapevine-shoot phenolic extract (Vineatrol 30) on early atherosclerosis in hamsters fed a hyperlipidic diet. Golden Syrian hamsters received for 13 weeks either a standard diet, a high-fat (HF) diet, or the HF diet plus Vineatrol 30 at 0.04, 0.2, or 1.0 mg/(kg body weight/d). We measured plasma lipids and glucose, insulin, leptin and adiponectin, as well as liver TNF-α and IL-6 levels. Oxidative stress was assessed by measuring plasma paraoxonase activity (PON) and liver superoxide anion production (O(2)(•-)). The aortic fatty streak area (AFSA) was also determined. In comparison with HF group, we demonstrated that the highest dose of Vineatrol 30 was capable of decreasing AFSA (67%), insulinemia (40%), and leptinemia (8.7%), which were increased by the HF diet. We also showed increased O(2)(•-) production (35%) and a rise in levels of the liver proinflammatory cytokines TNF-α (22%) and IL-6 (21%), accompanied by a fall in PON activity (56%) due to the HF diet versus the standard diet. In contrast, except plasma adiponectin levels that are not changed, Vineatrol 30 treatment lowered AFSA (67%), O(2)(•-) production (36%), insulin resistance (42%), leptinemia (9%), liver TNF-α (18%) and IL-6 (15%), while it rose PON activity (29%). These findings demonstrate the preventive effects of polyphenols present in Vineatrol 30 in managing cardiovascular, metabolic, and inflammatory risk factors.

Female stress incontinence is often the consequences of obstetrical traumatisms. They are responsible of a weakness of perineal musculoaponevrotic structures. Until 1996, the reference treatment of this pathology was the "Burch" colposuspension, by laparotomy, then laparoscopic way. After 1996, a new procedure was developped by Ulmten, reproducible, easy, safe and mini-invasive: the tension free-vaginal-tape (TVT) followed by the trans-obturator-tape (TOT). This therapeutic tool has become the reference for the treatment of the female stress incontinence. There are now 15 years from the beginning of this procedure and still 80% of the patients are improved., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

This study explored major systems of reactive oxygen species (ROS) production and their consequences on oxidative stress, mitochondriogenesis and muscle metabolism in aged rats, and evaluated the efficiency of 30-day oral supplementation with a moderate dose of a red grape polyphenol extract (RGPE) on these parameters. In the liver of aged rats, NADPH oxidase activity was increased and mitochondrial respiratory chain complex activities were altered, while xanthine oxidase activity remained unchanged. In muscles, only mitochondrial activity was modified with aging. The oral intake of RGPE decreased liver NADPH oxidase activity in the aged rats without affecting global oxidative stress, suggesting that NADPH oxidase was probably not the dominant detrimental source of production of O(2)·(-) in the liver. Interestingly, RGPE supplementation increased mitochondrial biogenesis and improved antioxidant status in the gastrocnemius of aged rats, while it had no significant effect in soleus. RGPE supplementation also decreased age-dependent autophagy in gastrocnemius of aged rats. These results extended existing findings on the beneficial effects of RGPE on mitochondriogenesis and muscle metabolism in aged rats.

The treatment of upper urinary tract stone with flexible ureteroscopy is safe and efficient. According to the size and the localization of stone, it is the first-line treatment. The patient must be informed about modalities and risks of this treatment. Urines must be sterile. The fragmentation of stone is made with the energy of Laser Holmium. The knowledge of material and technique allows to obtain a complete treatment in about 80% of cases., (Copyright © 2011. Published by Elsevier Masson SAS.)

Objective: To evaluate the functional and cancer results of radical prostatectomy with bladder neck preservation in the treatment of localized prostate cancer., Material and Method: From January 2000 to March 2006, 194 consecutive patients underwent open retropubic radical prostatectomy for localized prostate cancer. The bladder neck was technically preserved in 180 patients (93%). The mean age of these 180 patients was 63.2+/-6.1 years. The mean preoperative PSA was 9.38+/-6 ng/ml. The 180 patients were classified according to the Amico prognostic classification as low risk: 52.2%, intermediate risk: 37.8% and high risk: 10%. Operative specimens were examined by the same pathologist according to the Stanford technique. Positive surgical margin was defined as tumour tissue in contact with the ink of the operative specimen. For analysis of the functional results, patients were classified into three categories: continent without protection, stress incontinent, totally incontinent. Continence was evaluated at D10, one month, six months, one, two, three, four and five years. The mean follow-up was 44+/-25 months., Results: This series of 180 operative specimens comprised 64 (35.6%) cases of positive surgical margins and 112 (62.2%) pT3 cancers. No positive margins were observed in the bladder neck, either alone or associated with another positive margin. Seventy-one percent of patients were continent on D10 and at one month, 85% were continent at six months and 89% were continent at one year. Two cases of anastomotic stenosis were observed (1.2%)., Conclusion: Bladder neck preservation during open retropubic radical prostatectomy allows early continence in more than 70% of cases without increasing the risk of positive surgical margins.

Stress during pregnancy results in neurochemical and behavioral alterations observed throughout adulthood and aging. We here examined the impact of prenatal stress (PS) on cognitive functions in juvenile-4-week-old-rats, focusing on putative sex differences. Dams received an unpredictable 90-min duration contention stress between gestational day E17 and E20. Locomotion and learning ability were examined in offsprings between day P24 and P29 using actimetry, spontaneous alternation in the Y-maze, delayed alternation in the T-maze, and passive avoidance. Both male and female PS rats showed increased activity. In the Y-maze, diminished spontaneous alternation (males: -20%; females: -29%) were seen for PS rats compared to non-PS rats. The number of arm entries was unchanged among groups. In the T-maze, PS rats failed to perform delayed alternation, as shown by equal time spent and number of entries in both the novel and previously explored arms. In the passive avoidance test, PS resulted in significant impairments for female offspring only of both step-through latency and percentage of animals to criterion. PS thus induced severe learning impairments affecting both short-term and long-term memories that could be observed early in lifetime, in 4-week-old, juvenile rats. In addition, marked sex differences were evidenced, particularly in the passive avoidance response that may reflect differential developmental neuroadaptations in precise brain structures.

In this study we investigated whether the expression of alpha1B- and alpha2A-adrenoreceptor mRNAs is differently modulated by glucocorticoids in rat cultured anterior hypothalamus slices. Using a semi-quantitative reverse transcription-polymerase chain reaction assay, the level of the alpha1B-adrenoreceptor mRNA was significantly reduced in slices cultured in steroid free-medium when compared with that measured in standard medium (i.e. containing basal adrenosteroid plasma concentrations). In contrast, the expression of the alpha2A-adrenoreceptor mRNA was markedly increased. Finally, the ratio of alpha1B- versus alpha2A-mRNA levels was about 1.7 and 0.7 in standard and steroid-free medium, respectively. These responses were completely reversed by supplementation with corticosterone. These findings provide the first evidence that in vitro glucocorticoids may regulate, in an opposite manner, the expression of the alpha1B-and alpha2A-adrenoreceptor mRNAs in the hypothalamus. This kind of regulation could be related to steroid-dependent changes in the noradrenergic control of neuroendocrine secretions.

We have shown previously that noradrenaline (NA) stimulated or inhibited the release of corticotropin-releasing hormone (CRH) according to the availability of adrenal steroids. The aim of the present work was to examine whether the changes in the NA modulation of CRH release from hypothalamic neurons result from a steroid-induced plasticity of the adrenergic transduction pathways. From anterior hypothalamic slices cultured in standard medium (i.e., containing adrenal steroids at a final dilution of 61 +/- 9 ng/ml), (a) the stimulatory effect of NA on CRH release was reversed in a dose-dependent manner by increasing concentrations of the alpha1-adrenoreceptor antagonist prazosin, (b) activation of protein kinase C by acute treatment with phorbol 12-myristate 13-acetate (0.5 microM, 1 h) mimicked NA stimulation of CRH secretion, and (c) the activation of L-type Ca2+ channels by Bay K 8644 also produce an increased CRH secretion. In contrast, the inhibitory effect of NA on CRH secretion from slices cultured in steroid-free medium was markedly reversed by the alpha2-adrenoreceptor antagonist yohimbine, by pretreatment with pertussin toxin, or by the addition of 4-aminopyridine, a K+-channel blocker. Acute treatment with phorbol 12-myristate 13-acetate did not change the inhibitory NA effect. Moreover, all these effects were reversed by daily corticosterone supplementation, for as long as they were tested. These results are consistent with a steroid-dependent change in the nature of adrenergic receptors and its associated transduction pathways involved in the regulation of CRH secretion in the hypothalamus.

Understanding the mechanisms involved in the biogenesis of N-arachidonoylethanolamine (anandamide) and N-palmitoylethanolamine is important in view of the possible role of these lipids as endogenous cannabinoid substances. Anandamide (which activates cannabinoid CB1 receptors) and N-palmitoylethanolamine (which activates a CB2-like receptor subtype in mast cells) may both derive from cleavage of precursor phospholipid, N-acylphosphatidylethanolamine (NAPE), catalyzed by Ca(2+)-activated D-type phosphodiesterase activity. We report here that the de novo biosynthesis of NAPE is enhanced in a Ca(2+)-dependent manner when rat cortical neurons are stimulated with the Ca(2+)-ionophore ionomycin or with membrane-depolarizing agents such as veratridine and kainate. This reaction is likely to be mediated by a neuronal N-acyltransferase activity, which catalyzes the transfer of an acyl group from phosphatidylcholine to the ethanolamine moiety of phosphatidylethanolamine. In addition, we show that Ca2+-dependent NAPE biosynthesis is potentiated by agents that increase cAMP levels, including forskolin and vasoactive intestinal peptide. Our results thus indicate that NAPE levels in cortical neurons are controlled by Ca2+ ions and cAMP. Such regulatory effect may participate in maintaining a supply of cannabimimetic N-acylethanolamines during synaptic activity, and prime target neurons for release of these bioactive lipids.

A number of recent studies have suggested that interleukin-1beta (IL-1beta) is a major mediator contributing to the recruitment of the hypothalamo-pituitary-adrenal (HPA) axis following infectious aggressions. Central catecholamines modulate the response of the HPA axis. To investigate the importance of the afferent catecholaminergic pathways in a pathophysiological situation, we used the intraperitoneal (i.p.) IL-1beta injection (mimicking peripheral infections) and we investigated the effects on the HPA responses to IL-1beta of bilateral neurotoxic (6-OHDA) deletion of the ventral noradrenergic ascending bundle (VNAB-X). The VNAB is an essential stimulating pathway linking the brainstem and the paraventricular nucleus (PVN). We determined the time courses of a number of HPA variables up to 240 min after i.p. injection of IL-1beta. We followed: plasma ACTH and corticosterone (CORT) concentrations, AP POMC nuclear primary RNA transcripts, AP POMC nuclear intermediate transcript RNA, AP POMC cytoplasmic mRNA, and hypothalamus (HT) CRH cytoplasmic mRNA. Compared to sham-lesioned male rats, VNAB-X animals displayed: (1) a reduced increase in plasma ACTH, and to a lesser extent in CORT throughout the experimental period with a 85% inhibition at the peak (90 min); (2) an increase in AP POMC primary nuclear transcript and in AP POMC nuclear intermediate transcript RNAs which last 60 min, instead of sustained significantly higher levels up to 240 min; (3) a similar, although reduced inhibition in the corresponding POMC cytoplasmic mRNA; (4) an almost complete abolishment of the marked biphasic rise in HT CRH mRNA. In conclusion, activation of the HPA axis by peritoneal IL-1beta challenge involves CRH-producing neurons, and afferent catecholaminergic innervation of the PVN plays a crucial role in the signaling machinery linking the peritoneal aggression to the HPA axis.

An organotypic culture system of anterior hypothalamic slices was developed for studying the secretory responses of corticotropin-releasing hormone (CRH) neurons to corticosteroid-catecholamine interactions. The standard culture medium included 5% horse serum containing 50 micrograms/l cortisol. In 1- to 3-day cultures, the tissue viability was demonstrated by the presence of arginine vasopressin immunolabeled perikarya and axons in the paraventricular nucleus and by sustained tissue concentrations of CRH (around 50 pg/mg protein). However, immunoreactive CRH neurons were not detectable in cultures in the standard medium. Exposure of cultures to high K+ (56 mM) in the medium induced a ten-fold increase in basal CRH release which was completely abolished in a Ca(2+)-free medium containing 2 mM EGTA. Noradrenaline (NA) triggered CRH release in a dose-dependent (1-20 microM) and time-dependent (0.5-6 h) manner. Removal of corticosteroids from the media by charcoal treatment led to (1) the visualization of immunolabelled CRH perikarya and fibers and a 55% rise in CRH content of the paraventricular nucleus tissue and (2) to a five-fold increase in CRH release. Both effects were reversed by supplementation of the culture medium with corticosterone (50 micrograms/l). Under steroid-free conditions, NA (1-10 microM) not only failed to induce CRH release, but strongly inhibited the consistent baseline in CRH release. This was reminiscent of a similar corticosteroid-dependent inversion of the NA effect on the hypothalamic-pituitary-adrenal axis described in vivo. Overall, these results are direct evidence of complex corticosteroid-catecholamine interrelationships as major regulatory factors of the hypothalamic-pituitary-adrenal axis.

When injected through an intra-arterial (i. a.) cannula, LPS induced a rapid (15-30 min) and long-lasting (> 300 min) increase in plasma ACTH and corticosterone (CORT) levels. The duration of these responses depended on the LPS dose, and except for very small LPS doses, their amplitudes appeared independent of the dose of endotoxin. ACTH peaks (2,200 pg.ml-1) occurred between 30 and 120 min, whereas CORT always reached maximal levels at 120 min. Plasma Interleukin-1 beta (IL-1 beta) levels were always undetectable during the early phase of corticotropic stimulation, but increased strikingly 120 min after LPS injection. Increasing LPS doses, resulted in enhanced and prolonged IL-1 beta plasma circulating levels (up to 3.0 +/- 0.2 ng.ml-1). By contrast, no sub-cutaneous LPS dose used induced early increases in ACTH and CORT levels, whereas time-course of the hormonal response was evocative of the sustained phase of the corticotropic response to i. a. LPS, with both peaks occurring 120 min post-LPS. Increasing the s. c. LPS bolus 50-fold vs the i. a. dose did not affect the maximal amplitude of the ACTH response, whereas the amplitude of the CORT response, instead, appeared dependent on the LPS dose. On the other hand, even for the largest LPS doses, plasma IL-1 beta levels remained undetectable. Sub-cutaneous injection of LPS therefore appears as a new model for the study of the mechanisms of corticotropic responses to endotoxin without a direct involvement of bloodborne IL-1 beta.

We recently showed that bilateral neurotoxic microlesions (6-OH-DA) of the ventral noradrenergic ascending bundle (VNAB-X) at stereotaxic coordinates that blocked corticotropic stress responses did not affect the ACTH surge after bilateral intra-paraventricular (i.PVN) injections of interleukin-1 beta (IL-1 beta), and that lesioning at these stereotaxic coordinates obliterated the dorsal axonal populations of the VNAB (dVNAB-X), but spared the bundle's most ventral axons (vVNAB). The present study compares the effects of IL-1 beta given i.PVN (2 x 5 ng) of intra-arterially (i.a.) (100 ng) on plasma ACTH in rats with bilateral 6-OH-DA microlesions placed in the dVNAB or the vVNAB, or in an intermediary central position (cVNAB-X). Unlike our previous results, in which dVNAB-X did not alter the biphasic ACTH response to i.PVN IL-1 beta, both vVNAB-X and cVNAB-X reduced by 50-75% the early and delayed ACTH surges which are typical of the i.PVN route. On the other hand the swift monophasic ACTH surge usually occurring after an i.a. injection of IL-1 beta was 65% smaller after dVNAB-X, but was doubled after vVNAB-X or cVNAB-X. Hence, the release of ACTH after both i.PVN or i.a. IL-1 beta requires brainstem afferences conveyed to the hypothalamus by the VNAB. However, the VNAB appears to include at least two functionally different subsets of axons, the roles of which in the ACTH response to IL-1 beta depend on the route by which the cytokine is given.

The hypothalamic-pituitary-adrenocortical (HPA) axis knowingly plays a key role in the physiological response to various stressing situations, owing to its gluconeogenetic function, and also, possibly, to its large range of modulating effects on a series of more specific defense mechanisms including the immune system, the latter effect serving to protect the organism against overactive defense reactions. It has long been accepted that under most aggressive conditions the CNS is an essential part of the mechanism controlling the subsequent acute stimulation of the HPA axis. In this line of research, the HPA axis reacts within a few minutes after a standard ether-stress, with a 6 fold increase over the baseline of CRH41 secretion, and at the periphery with 20-fold and 14-fold increases, respectively, in plasma concentrations of ACTH and corticosterone in unanesthetized free-moving rats. From a series of additional experiments a few selected brain structures emerged as basic components of the CNS control involved in the HPA axis stress responses: 1) The catecholamine (CA) producing neurons of the medulla oblongata (A1/C1 and A2/C2 nuclei) which directly innervate the CRH41-secreting neurons in the paraventricular nuclei (PVN) via the ventral noradrenergic bundle (VNAB), yield the major stimulatory pathway to the stress-induced CRH-ACTH surge. Not only was this surge dramatically obliterated by a neurotoxic deletion of the VNAB, with a local microinfusion of 6-hydroxydopamine (6-OHDA) but it was restored by intra-cerebroventricular (icv) microinfusions of adrenaline (AD) or noradrenaline (NA).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of various stressors (restraint, ether, histamine and insulin-induced hypoglycemia stress) on the early time course activation of the different catecholaminergic (CA) cell groups A1/C1, A2/C2 and locus ceruleus (LC) from the brainstem were studied. The activity of the central noradrenergic neurons was assessed by measuring in tissue punches the 3,4-dihydroxyphenylacetic acid (DOPAC) level, a side metabolite of noradrenaline (NA) and adrenaline biosynthesis that is thought to reflect the activity of NA cells. Short 5 min restraint stress led to an immediate increase of DOPAC level in the three CA groups. In the A1/C1 and A2/C2 groups the maximal increase, respectively +75 and +50%, was already reached at the end of the application of the stress while for the LC the maximum (+84%) was obtained 15 min after the onset of the stress. Return to baseline level was achieved within 2 h. Continuous immobilization stress did not further alter the DOPAC concentration in the LC and the A1/C1 while a progressive increase up to 85% in the A2/C2 group was seen over 20 min. Following a 2-min exposure to ether, DOPAC was increased in all three structures within 5 min. At this time the maximum was already reached in the A1/C1 and LC, respectively +99 and +43%. After histamine or insulin injection DOPAC level increased in the A1/C1 and A2/C2 in the +25/+50% range but was not significantly affected in the LC. In all the stress situations studied the increase in DOPAC level, particularly in the A1/C1 group always preceded or was concomitant to the increase of plasma corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

We have recently assigned a major stimulatory role to the brain catecholamines (CA) via alpha 1 and beta receptors on CRH-ACTH secretion, e.g. in the physiological response to stress. In the present study, we explored the possible participation in this regulation of post-synaptic alpha 2 receptors in free moving rats, one week after CA denervation of the hypothalamus by bilateral neurotoxic lesions of the noradrenergic ascending brain stem bundles (NAB). Intracerebroventricular (i.c.v.) injection of clonidine (alpha 2 agonist; 1 nmol) induced a 3 fold rise of ACTH release (measured by RIA) above vehicle (PBS) injected controls (p less than 0.001). This stimulatory effect was completely reversed by an i.c.v. pretreatment with the alpha 2 antagonist idazoxan (10 nmol; without action by itself), whereas it was only slightly affected by an i.c.v. pretreatment with a combination of an alpha 1 and beta blocker (prazosin + propranolol; 5/5 nmol; p greater than 0.1). The results strongly suggest the participation of alpha 2 post-synaptic receptors in the central catecholaminergic activation of ACTH secretion.