Interleukin-6 deletion in mice driven by aP2-Cre-ERT2 prevents against high-fat diet-induced gain weight and adiposity in female mice.

AIM: Interleukin-6 (IL-6) is a major cytokine controlling body weight and metabolism, but because many types of cells can synthesize and respond to IL-6 considerable uncertainty still exists about the mechanisms underlying IL-6 effects. Therefore, the aim of this study was to analyse the effects of tissue-specific deletion of IL-6 using a fatty acid binding protein (aP2) promoter-Cre inducible system (aP2-Cre-ERT2). METHODS: Tissue-specific IL-6 KO mice (aP2-IL-6 KO mice) were produced upon tamoxifen administration and were fed a high-fat diet (HFD, 58.4% kcal from fat) or a control diet (18%) for 14 weeks. RESULTS: aP2-IL-6 KO female mice on a HFD gained less weight and adiposity than littermate wild-type mice, but these effects were not observed in males. Hypothalamic factors such as NPY and AgRP showed a pattern of expression consistent with this sex-specific phenotype. PGC-1α expression was increased in several tissues in aP2-IL-6 KO female mice, which is compatible with increased energy expenditure. Serum leptin, insulin, glucose, cholesterol and triglycerides levels were increased by HFD, and in females IL-6 deficiency reversed this effect in the case of insulin and cholesterol. HFD induced impaired responses to insulin and glucose tolerance tests, but no significant differences between genotypes were observed. CONCLUSION: The present results demonstrate that deletion of IL-6 driven by aP2-Cre regulates body weight, body fat and metabolism in a sex-specific fashion.

Interleukin-6 regulates the expression of hypothalamic neuropeptides involved in body weight in a gender-dependent way.

Interleukin (IL)-6 has been involved in the control of body weight and body fat. Nevertheless, the mechanisms underlying these effects are not completely understood because central and peripheral actions of IL-6 are plausible. To gain further insight into the central effects of IL-6, we used transgenic mice expressing the IL-6 gene under the control of the glial fibrillary acidic protein (GFAP) promoter (GFAP-IL-6 mice), therefore with central nervous system-restricted over-expression of IL-6, and we studied the expression of the main neuropeptides responsible for energy homeostasis in specific hypothalamic nuclei. Neuropeptide Y (NPY), agouti-related peptide (AgRP), melanin-concentrating hormone (MCH), prepro-orexin (preproOX) (orexigenic and anabolic neuropeptides), pro-opiomelanocortin (POMC) and corticotrophin-releasing hormone (CRH) (anorexigenic and catabolic peptides) mRNA levels were determined using in situ hybridisation in young (2-4 month-old) and old (10-12 month-old) female and male mice under different feeding conditions: normal diet (control) and high-fat diet (HFD), and 24 h-food deprivation. In GFAP-IL-6 females fed a control diet (GFAP-IL-6-control), we showed a significant decrease in NPY and AgRP mRNA levels at all ages, and a late increase in POMC expression (only significant in older animals). These differences were blunted in HFD mice. By contrast, GFAP-IL-6-control males showed a decrease in CRH mRNA content at early ages (2-4 months), and an increase in older mice (10-12 months). Interestingly, these differences were again blunted in HFD mice. Finally, central IL-6 was not able to counteract the effects of 24 h of fasting on body weight, plasma glucose levels and the mRNA content of the peptides evaluated in the present study. Our results demonstrate that IL-6 may regulate the expression of hypothalamic neuropeptides involved in the control of body weight and body fat acting at the central level in a gender- and age-dependent way.

Efficacy and safety of a new Botulinum Toxin Type A free of complexing proteins in the treatment of blepharospasm.

NT 201 is a new development of Botulinum Toxin Type A free of complexing proteins. In this double-blind Phase III trial, we compared the efficacy and safety of NT 201 and BOTOX in patients suffering from blepharospasm. Of 304 enrolled patients, 300 patients received study medication (intent-to-treat population), and 256 patients completed the study as planned (per-protocol population). At baseline, patients received a single injection of NT 201 or BOTOX (

A new botulinum toxin type A free of complexing proteins for treatment of cervical dystonia.

A new botulinum toxin type A free of complexing proteins (NT 201) was compared with BOTOX in patients with cervical dystonia by means of a double-blind noninferiority trial. Four hundred sixty-three patients received IM injections of 70 to 300 U of NT 201 or BOTOX and were followed up over 16 weeks. The study clearly shows that NT 201 is at least as effective and safe as BOTOX.

Efficacy and tolerability of a botulinum toxin type A free of complexing proteins (NT 201) compared with commercially available botulinum toxin type A (BOTOX) in healthy volunteers.

PURPOSE: This randomized controlled trial was performed to compare the novel botulinum toxin type A free of complexing proteins (NT 201) with the marketed preparation BOTOX degrees regarding efficacy and tolerability. METHODS: Fourteen healthy volunteers received a single intramuscular injection into the extensor digitorum brevis (EDB) muscle of either 4 units NT 201, or 4 units of BOTOX degrees randomised by foot. Compound muscle action potential (CMAP) measurements were recorded for up to 90 days after injection. RESULTS: Both drugs produced a maximum decline between Day 7 and Day 14. At Day 90, administration of both drugs resulted in approximately a 40% CMAP decline as compared to baseline. Duration of paralytic effect was comparable in both groups, at all response thresholds tested. Both drugs were well tolerated. CONCLUSION: The effects of small amounts of NT 201 and BOTOX degrees injected into the EDB muscle are comparable in terms of efficacy, time to onset of action, duration of action, and tolerability.

Effect of continuous antistaphylococcal therapy on the rate of P. aeruginosa acquisition in patients with cystic fibrosis.

SUMMARY. Continuous therapy with antistaphylococcal antibiotics is advocated by some cystic fibrosis (CF) centers, but it is unclear whether this strategy favors early colonization with P. aeruginosa. We used the data base for the German Centers of the European Registry for Cystic Fibrosis (ERCF) to assess the effect of continuous antistaphyloccocal therapy on the rate of P. aeruginosa acquisition in CF patients. Patients included in this analysis had to be < 18 years of age, P. aeruginosa-negative prior to entry in the ERCF, and to have had at least 2 additional P. aeruginosa-negative respiratory cultures while followed in the ERCF. Of the 639 patients fulfilling these criteria, 48.2% received continuous antistaphyloccocal therapy, 40.4% intermittent antibiotic therapy, and 11.4% no antibiotic therapy. There were no differences between the groups in body mass index, as well as forced vital capacity (FVC) and forced expired volume in 1 sec (FEV(1)) at baseline. The rate at which patients acquired positive respiratory cultures for Staph. aureus was significantly lower in the group receiving continuous antistaphyloccocal antibiotic therapy than in those not receiving such therapy. Patients receiving continuous antistaphyloccocal antibiotic therapy had a significantly higher rate of P. aeruginosa acquisition compared to patients receiving only intermittent or no antibiotic therapy. This difference was especially apparent for children younger than age 6 years. We conclude that continuous therapy with antistapyloccocal antibiotics directed against Staph. aureus increases the risk of colonization with P. aeruginosa. How this affects the clinical outcome of these patients remains to be determined.

[Effect of enalapril on microalbuminuria and lipid profile of normotensive type I diabetes mellitus patients]. / Influencia de enalapril sobre la microalbuminuria y el perfil lipídico en pacientes con diabetes mellitus tipo I normotensos.

A longitudinal study for six months was conducted to demonstrate the influence of enalapril therapy on microalbuminuria in a group of patients with IDDM without arterial hypertension. An evaluation was also considered of its possible activity on other biochemical parameters, particularly plasma lipid levels. Thirty-four patients with IDDM were selected, with a mean age of 26.1 +/- 7.2 years and a mean clinical course of 11.8 +/- 5.6 years. Arterial blood pressure (ABP) was confirmed lower than 140/85 mmHg in all cases. Patients were administered 5 mg/day of enalapril and if a decrease in microalbuminuria higher than 25% was not achieved at the end of the first month of therapy, the dose was doubled (10 mg/day). No significant differences were found in ABP and in HbA1c throughout the study period. Albumin excretion in the initial period was 125.1 +/- 79.28 mg/24 h, at one month in the follow-up 47.6 +/- 44.1 mg/24 h, at three months 23.8 +/- 18.1 mg/24 h, and at the end of the 6th month 15.33 +/- 6.9 mg/24 h, all differences being significant. Renal function parameters and Na+ and K+ measurements remained unchanged for the follow-up period. No significant changes were detected for lipid and lipoprotein values for the length of the study. We conclude that therapy with enalapril in insulin-dependent diabetic patients without hypertension has an important effect on microalbuminuria during the first month of therapy; a stabilization in the normal range was reached in the third and sixth months of follow-up. No changes in arterial blood pressure nor in renal function were observed. Plasma lipid values were in the normal range throughout the study. Therefore, treatment for microalbuminuria with the ACEI assayed was efficient, in absence of arterial hypertension and irrespective of the metabolic control obtained. Future long-term studies are needed to evaluate the possible delay in the emergence of renal insufficiency.

[Spiegelian hernia. Apropos of a series of 31 cases]. / Les hernies de Spiegel. A propos d'une série de 31 cas.

31 cases of spiegelian hernias are reported. It is one of the world biggest statistics of this affection. The patients were divided in 18 women and 13 men, with an average of 45 years old. The hernia was located on the right side of the abdomen in 16 cases and on the left side in 13 cases. In two cases, the affection was bilateral. In 14 cases, there was an incarceration. No strangulation was observed. The rare forms can be divided in massive form, tumoral, crawling (in the old man), spread (in the infant and the woman). The spiegelian hernia can be associated with one or more other kinds of hernias. 27 patients underwent an operation. In all the cases, an direct approach was used. There was no post operative complications. We want to emphazise the high frequence of this affection in Gabon, and the fact that most of the cases have been observed within the same area, in the south of the country. A study researching predictive factors could be interesting to be realised in this area.