Kinin B1 Receptor Enhances the Oxidative Stress in a Rat Model of Insulin Resistance: Outcome in Hypertension, Allodynia and Metabolic Complications

BACKGROUND: Kinin B(1) receptor (B(1)R) is induced by the oxidative stress in models of diabetes mellitus. This study aims at determining whether B(1)R activation could perpetuate the oxidative stress which leads to diabetic complications. METHODS AND FINDINGS: Young Sprague-Dawley rats were fed with 10% D-Glucose or tap water (controls) for 8-12 weeks. A selective B(1)R antagonist (SSR240612) was administered acutely (3-30 mg/kg) or daily for a period of 7 days (10 mg/kg) and the impact was measured on systolic blood pressure, allodynia, protein and/or mRNA B(1)R expression, aortic superoxide anion (O(2)(*-)) production and expression of superoxide dismutase (MnSOD) and catalase. SSR240612 reduced dose-dependently (3-30 mg/kg) high blood pressure in 12-week glucose-fed rats, but had no effect in controls. Eight-week glucose-fed rats exhibited insulin resistance (HOMA index), hypertension, tactile and cold allodynia and significant increases of plasma levels of glucose and insulin. This was associated with higher aortic levels of O(2)(*-), NADPH oxidase activity, MnSOD and catalase expression. All these abnormalities including B(1)R overexpression (spinal cord, aorta, liver and gastrocnemius muscle) were normalized by the prolonged treatment with SSR240612. The production of O(2)(*-) in the aorta of glucose-fed rats was also measured in the presence and absence of inhibitors (10-100 microM) of NADPH oxidase (apocynin), xanthine oxidase (allopurinol) or nitric oxide synthase (L-NAME) with and without Sar[D-Phe(8)]des-Arg(9)-BK (20 microM; B(1)R agonist). Data show that the greater aortic O(2)(*-) production induced by the B(1)R agonist was blocked only by apocynin. CONCLUSIONS: Activation of kinin B(1)R increased O(2)(*-) through the activation of NADPH oxidase in the vasculature. Prolonged blockade of B(1)R restored cardiovascular, sensory and metabolic abnormalities by reducing oxidative stress and B(1)R gene expression in this model

Religion for the political rights of immigrants and refugees? An empirical exploration among Italian students

Contains fulltext : 198187pub.pdf (publisher's version ) (Closed access)This article focuses on the support, or lack of support, for political rights of immigrants and refugees. Confronted with relatively big groups of migrants and refugees in the Southern part of the country, Italian youth is a highly relevant population to ask the following question: whose rights are human rights? Are political rights the property of all people residing in a country, or can they only be claimed by its citizens? This question is not merely an academic one; it touches the lives of more than ten thousand migrants arriving on the Italian shores every month while risking their lives. This burning issue engages intensely political voices and actors in civil society. One among the latter, the Catholic Church, has become more vocal in the last years in advocating an extension of the rights of immigrants and refugees, sometimes even creating a public clash between bishops’ statements and the voices of those politicians who express populist and xenophobic ideas. This contribution concerns the role of the Catholic Church in Italy’s debate about the political rights of foreigners; not only at the level of public statements and official teachings of the Catholic hierarchy but also at the level of Italian students’ opinions on these matters

Inter-population variability and character description in the sponge-associated Haplosyllis spongicola complex (Polychaeta: Syllidae)

18 páginas, 17 figuras, 3 tablas.Haplosyllis spongicola is probably the most representative symbiotic syllid harboured by sponges and has been widely reported from tropical, subtropical and temperate seas. Its external morphology seems to be very well adapted for its life-style, with all chaetae being simple and having two small teeth and a large main fang. However, the species has been the subject of a long-lasting taxonomic controversy, which gave rise to more than 15 synonymies, with hundreds of records worldwide. The present paper is based on the study of more than 28 populations obtained from around the world. These populations have been carefully analysed using different approaches (morphometry, morphology and biology). As a consequence, the existence of a pseudo-sibling species-complex within the socalled cosmopolitan H. spongicola has been revealed. The most relevant characters (as well as their variability) that will allow a future identification of the species involved in the complex are fully described, illustrated and analysed.The study has been partly financed by a research contract between the CEAB (CSIC) and French company CREOCEAN and has been partly sponsored by TOTAL. This paper is a contribution to the research project INTAS–OPEN–97–0916.Peer reviewe

Genetically Encoded Fluorescent Biosensors to Explore AMPK Signaling and Energy Metabolism

International audienceMaintenance of energy homeostasis is a basic requirement for cell survival. Different mechanisms have evolved to cope with spatial and temporal mismatch between energy-providing and -consuming processes. Among these, signaling by AMP-activated protein kinase (AMPK) is one of the key players, regulated by and itself regulating cellular adenylate levels. Further understanding its complex cellular function requires deeper insight into its activation patterns in space and time at a single cell level. This may become possible with an increasing number of genetically encoded fluorescent biosensors, mostly based on fluorescence resonance energy transfer, which have been engineered to monitor metabolic parameters and kinase activities. Here, we review basic principles of biosensor design and function and the advantages and limitations of their use and provide an overview on existing FRET biosensors to monitor AMPK activation, ATP concentration, and ATP/ADP ratios, together with other key metabolites and parameters of energy metabolism

Polypharmacy Patterns: Unravelling Systematic Associations between Prescribed Medications

OBJECTIVES: The aim of this study was to demonstrate the existence of systematic associations in drug prescription that lead to the establishment of patterns of polypharmacy, and the clinical interpretation of the associations found in each pattern. METHODS: A cross-sectional study was conducted based on information obtained from electronic medical records and the primary care pharmacy database in 2008. An exploratory factor analysis of drug dispensing information regarding 79,089 adult patients was performed to identify the patterns of polypharmacy. The analysis was stratified by age and sex. RESULTS: Seven patterns of polypharmacy were identified, which may be classified depending on the type of disease they are intended to treat: cardiovascular, depression-anxiety, acute respiratory infection (ARI), chronic obstructive pulmonary disease (COPD), rhinitis-asthma, pain, and menopause. Some of these patterns revealed a clear clinical consistency and included drugs that are prescribed together for the same clinical indication (i.e., ARI and COPD patterns). Other patterns were more complex but also clinically consistent: in the cardiovascular pattern, drugs for the treatment of known risk factors—such as hypertension or dyslipidemia—were combined with other medications for the treatment of diabetes or established cardiovascular pathology (e.g., antiplatelet agents). Almost all of the patterns included drugs for preventing or treating potential side effects of other drugs in the same pattern. CONCLUSIONS: The present study demonstrated the existence of non-random associations in drug prescription, resulting in patterns of polypharmacy that are sound from the pharmacological and clinical viewpoints and that exist in a significant proportion of the population. This finding necessitates future longitudinal studies to confirm some of the proposed causal associations. The information discovered would further the development and/or adaptation of clinical patient guidelines to patients with multimorbidity who are taking multiple drugs