New antiobesity agents in type 2 diabetes: overview of clinical trials with sibutramine and orlistat.

Besides genetic predisposition, obesity is the most important risk factor for the development of type 2 diabetes mellitus. Even modest weight reduction can improve blood glucose control in overweight subjects. After failure of lifestyle modifications, antiobesity drugs such as orlistat, a potent and selective inhibitor of gastric and pancreatic lipases that reduces lipid intestinal absorption, or sibutramine, a noradrenaline and 5-hydroxytryptamine reuptake inhibitor that regulates food intake, may be considered to favour weight loss and/or weight maintenance. Several placebo-controlled studies have recently demonstrated that both drugs are able to promote weight loss in obese type 2 diabetic patients treated with diet alone, sulphonylureas, metformin or insulin. The greater weight reduction as compared to placebo was associated with a significant reduction of glycated haemoglobin levels and/or of the doses of classical antihyperglycaemic agents, especially in good responders who lost at least 10% of initial body weight. In addition, vascular risk factors associated to insulin resistance were also reduced after weight loss. These antiobesity agents may also contribute to delay or prevent the progression from impaired glucose tolerance to overt type 2 diabetes in at risk obese individuals ("Xenical in the prevention of diabetes in obese subjects" trial). Large long-term prospective studies, such as the "Sibutramine cardiovascular and diabetes outcome study" should better determine the place of pharmacological anti-obesity strategy in the overall management of obese patients with impaired glucose tolerance or type 2 diabetes

Renal SGLT2 inhibitors, new agents for the management of type 2 diabetes

Kidney plays a role in glucose homeostasis, not only by its capacity to produce glucose through local gluconeogenesis, but also, and even more important in presence of diabetes, by its capacity to excrete glucose in urine when hyperglycaemia exceeds tubular reabsorption threshold. Such reabsorption depends on sodium-glucose cotransporters-2 (SGLT2), which can be blocked by selective inhibitors. These pharmacological agents augment glucosuria and reduce hyperglycaemia independently of insulin. Some have already proven their efficacy to improve glucose control, in monotherapy or in combination, while promoting weight loss and without inducing hypoglycaemia. Dapagliflozin should be the first medication of this new pharmacological class to be commercialized for the management of type 2 diabetes

Report on the Second Symbol Recognition Contest

http://www.springer.com/lncsFollowing the experience of the first edition of the international symbol recognition contest held during GREC'03 in Barcelona, a second edition has been organized during GREC'05. In this paper, first, we bring to mind the general principles of both contests before presenting more specifically the details of this last edition. In particular, we describe the dataset used in the contest, the methods that took part in it, and the analysis of the results obtained by the participants. We conclude with a synthesis of the contributions and lacks of these two editions, and some leads for the organization of a forthcoming contest

Spacecraft Data Handling Architecture based on AFDX network

International audienceThe Mission project (Methodology and assessment for the applicability of ARINC-664 (AFDX)[4] in Satellite/Spacecraft on-board communicatION networks), as an FP7 initiative for bringing terrestrial SME research into the space domain, aims to apply the Integrated Modular Avionics (IMA) concept on spacecraft, together with highly deterministic interconnected on-board network (ARINC-664, AFDX). It will constitute an enabling technology harmonization and standardization action. Together with an intrinsic improvement of systems performance, product assurance and reliability, it is expected to provide multiple benefits at all industrial level such as standardized and configurable systems, products and technology elements, easier and faster integration of complex systems, larger procurement basis, and easier subcontracting scheme. This paper presents the project objectives, architecture design, proof of concept demonstrator and current progress

A Theoretical Study of Models for X2Y2 Zintl Ions

Ab initio and extended Hückel calculations have been used to discuss the bonding scheme in X₂Y₂ neutral and ionic main group clusters. A qualitative analysis suggests that two different electron counts, 20 and 22, are possible for the butterfly structures of these systems. This results from two orbital crossings in the correlation diagram for the tetrahedral (T_d) -\u3e butterfly (C_2v) -\u3e square-planar (D_2h) transformation. Detailed ab initio computations substantiate this analysis and show that the 20-electron butterfly structure becomes increasingly favored over the tetrahedral one in X₂Y₂ clusters when the 2 atoms have increasing electronegativity difference. These results are in agreement with the known structures for the Pb₂Sb₂²­­­­­­̄ and Sb₂Bi₂²­­­­­­̄ clusters (tetrahedral-like) and the Tl₂Te₂²­­­­­­̄ one (butterfly-like)

Influence Of Mitragyna ciliate (Myta) On The Microsomal Activity Of ATPase Na+/K+ Dependent Extract On A Rabbit Heart.

Mitragyna ciliate (MYTA) (Rubiaceae) inhibits plasmodia activity. MYTA induces a cardiotonicity of the digitalic type on rat\'s isolated heart. In this work we studied the effect of MYTA on microsomal Na+/K+ - dependant ATPase (Na+, K+ ATPase) extracted from the heart of a rabbit since digitalics inhibit Na+, K+ ATPase. Our results revealed that the Na+/K+ ATPase has an optimum pH of 7.4 and temperature of 37oC respectively. There is a linear relationship between the organic phosphate formed and the incubation time over 25 mins incubation period. The ATP hydrolysis rate in the presence of MYTA was 0.775 μM/min. LINEWEAVER and BURK plots showed that MYTA did not alter KM (1.31 mM) but decreased VMAX. This study shows that MYTA exerts a non-competitive inhibition on the microsomal Na+/K+ ATPase extracted from rabbit heart with a Ci50 of 48 μg / ml. We conclude that the mechanism of action of MYTA is linked to the inhibition of the Na+/K+ ATPase like cardiotonics of the digitalic type. Keywords: Mitragyna ciliate; ATPase Na+/K+; inhibitors of ATPase Na+/K+.African Journal of Trad, Comp and Alternative Medicine Vol. 5 (3) 2008: pp.294-30

The Quebec newborn twin study at 21

This paper is a revised and updated edition of a previous description of the Quebec Newborn Twin Study (QNTS), an ongoing prospective longitudinal follow-up of a birth cohort of twins born between 1995 and 1998 in the greater Montreal area, Québec, Canada. The goal of QNTS is to document individual differences in the cognitive, behavioral, and social-emotional aspects of developmental health across childhood, their early genetic and environmental determinants, as well as their putative role in later social-emotional adjustment, school, health, and occupational outcomes. A total of 662 families of twins were initially assessed when the twins were aged 6 months. These twins and their family were then followed regularly. QNTS now has 16 waves of data collected or planned, including 5 in preschool. Over the last 24 years, a broad range of physiological, cognitive, behavioral, school, and health phenotypes were documented longitudinally through multi-informant and multimethod measurements. QNTS also entails extended and detailed multilevel assessments of proximal (e.g., parenting behaviors, peer relationships) and distal (e.g., family income) features of the child’s environment. QNTS children and a subset of their parents have been genotyped, allowing for the computation of a variety of polygenic scores. This detailed longitudinal information makes QNTS uniquely suited for the study of the role of the early years and gene–environment transactions in development