Double deletion of orexigenic neuropeptide Y and dynorphin results in paradoxical obesity in mice

Objective

Orexigenic neuropeptide Y (NPY) and dynorphin (DYN) regulate energy homeostasis. Single NPY or dynorphin deletion reduces food intake or increases fat loss. Future developments of obesity therapeutics involve targeting multiple pathways. We hypothesised that NPY and dynorphin regulate energy homeostasis independently, thus double NPY and dynorphin ablation would result in greater weight and/or fat loss than the absence of NPY or dynorphin alone.

Design and methods

We generated single and double NPY and dynorphin knockout mice (NPYΔ, DYNΔ, NPYDYNΔ) and compared body weight, adiposity, feeding behaviour, glucose homeostasis and brown adipose tissue uncoupling protein-1 (UCP-1) expression to wildtype counterparts.

Results

Body weight and adiposity were significantly increased in NPYDYNΔ, but not in NPYΔ or DYNΔ. This was not due to increased food intake or altered UCP-1 expression, which were not significantly altered in double knockouts. NPYDYNΔ mice demonstrated increased body weight loss after a 24-h fast, with no effect on serum glucose levels after glucose injection.

Conclusions

Contrary to the predicted phenotype delineated from single knockouts, double NPY and dynorphin deletion resulted in heavier mice, with increased adiposity, despite no significant changes in food intake or UCP-1 activity. This indicates that combining long-term opioid antagonism with blockade of NPY-ergic systems may not produce anti-obesity effects.     

DC-SIGN polymorphisms are associated to type 1 diabetes mellitus

Type I diabetes mellitus (T1DM) is an autoimmune disorder featured by raised glucoses levels. It has been hypothesised that raised glucose levels in T1DM might be recognised as PAMPs, leading to immune response by overloading the cell receptors for pathogens recognition. DC-SIGN is a transmembrane protein, present in dendritic cells (DC) and macrophages: it has an important role in inflammatory response and T cells activation. Notably, DC-SIGN activation and triggering of the immune response depend on the type of ligand, which may lead to a pro or anti-inflammatory pathway. In our association study, we analysed the SNPs rs4804803 (−336 A>G) and rs735239 (−871 A>G), both at DC-SIGN promoter region, in 210 T1DM patients and 157 healthy controls, also looking for a correlation with the age of onset of the disease. We found that the allele G and genotypes G/G and A/G of SNP-871 (rs735239), as well as the alleles G-G (rs735239-rs4804803) and genotypes combined AA-GG (rs735239-rs4804803) were associated with protection of T1DM development. We did not find association between these variations with the age of onset of the disease and the presence of other autoimmune disorders. Our results suggest that SNPs in DC-SIGN promoter region can be associated to protection for T1DM in the Northeast Brazilian population.     

Humoral immunity patterns based on antibody reactivity to rotavirus antigens in Brazilian children under 5 years of age

The age distribution of antibody to simian rotavirus (SA-11) was studied in serum specimens obtained from 399 children aged to 5 years and living in the city of Recife (PE), located in the north eastern region of Brazil. Sera were examined for group-specific rotavirus antibody using a blocking enzyme immunoassay (bELISA) and a hemagglutination inhibition antibody (HIA) test, and for anti-VP2, anti-VP4, anti-VP6, and anti-VP7 antibodies using an immunoblotting assay (IBA). Antibody prevalence was similar in all bELISA and HIA assays, showing a steep rise in the 6- to 17-month-old age groups. The results indicate early acquisition of antibody to rotavirus. The majority of children aged 2 to 4 years had bELISA (50% to 60%) and HIA (70% to 81%) antibodies. There was an association in prevalence data obtained by HIA and bELISA with immunoblotting (IBA), revealing four serologic profiles. Children with profiles I and II (60%) respectively had HAI and ELISA antibody or HAI antibody alone and all had immunoprotective antibodies to VP4 and/or VP7. These children were regarded as “immune,” resembling convalescent patients with a rotavirus infection. Children with profile III (4%) had no HIA antibody and only non-protective anti-VP6 and/or VP7 antibody, and were considered to be “partially immune.” Children with profile IV (36%) had no detectable antibody and were classified as “nonimmune.” These children should be considered to be susceptible to rotavirus infection, with the risk of developing clinically severe diarrhea. © 1996 Wiley-Liss, Inc.     

Palatable high-fat diet intake influences mnemonic and emotional aspects in female rats in an estrous cycle-dependent manner

Metabolic Brain Disease - Worldwide, the excessive consumption of fat and/or sugar has increased considerably. Palatable high-fat diets (HFDs) lead to metabolic disturbances and obesity,...     

Comparative effect of an essential oil mouthrinse on plaque,gingivitis and salivary Streptococcus mutans levels: a double blind randomized study

An open, randomized, controlled study with two parallel treatment groups was done to evaluate the efficacy of a Lippia sidoides essential oil (EO) 1% mouthrinse compared with chlorhexidine 0.12% mouthrinse, applied two times daily for 1 week, in the treatment of dental plaque and gingivitis. Fifty‐five patients were included in the study. The efficacy variables were the colony count of Streptococcus mutans from the stimulated saliva and periodontal indices on days 0, 7 and 30 after commencement of therapy. Twenty eight patients received chlorhexidine mouthrinse (Periogard^®) and 27 Lippia sidoides essential oil mouthrinse (Cepakill^®). The clinical and microbiological parameters were significantly reduced by both mouthrinses. No significant difference was seen between the two groups (p > 0.05). There was a significant reduction in the colony count of S. mutans in both groups (p < 0.05). Chlorhexidine treatment reduced more efficiently than L. sidoides, however, no statistical difference was seen, the efficacy of both groups was similar (p = 0.3). The results indicate that Chlorhexidine mouthrinse reduced plaque index, gingival bleeding and the number of CFU (colonies forming units) more efficiently than L. sidoides but did not reach statistical significance. This study demonstrated that Lippia sidoides EO mouthrinse is effective in reducing microbial plaque and gingival inflammation. Copyright © 2009 John Wiley & Sons, Ltd.     

Optimizing costs of intraoperative magnetic resonance imaging. A series of 29 glioma cases

Purpose  

The goal of this study was to develop a method to reduce the costs of intraoperative high-field magnet resonance imaging (iMRI). The results of a series of 29 gliomas removed with this technique are presented.