Mechanisms of the hypoglycemic effects of the alpha2-adrenoceptor antagonists SL84.0418 and deriglidole

The effects of the alpha2-adrenoceptor antagonist SL84.0418 and its two enantiomers, (+) deriglidole and (-)SL86.0714 on glucose and insulin levels were examined in mice and in neonatal streptozotocin-induced diabetic rats. It was recently demonstrated in mouse pancreatic beta-cells that both deriglidole and SL86.0714 inhibit ATP-sensitive K+ channel with similar potency whereas alpha2-adrenoceptors are blocked only by deriglidole. In the present study, we showed, in vivo in mice, that SL84.0418 and deriglidole potently reduced glycemia and antagonized diazoxide-induced hyperglycemia, whereas SL86.0714 and tolbutamide were markedly less potent. In diabetic rats, SL84.0418 and deriglidole (10 mg/kg i.p.) fully normalized glucose tolerance whereas SL86.0714 and tolbutamide only slightly improved it. Five min after deriglidole administration in mice a marked and short lasting rise in insulin levels was observed, followed by a progressive reduction of glycemia. In diabetic rats, insulin and norepinephrine levels rose 15 min after deriglidole administration. Sympathetic outflow blockade by chlorisondamine, beta-adrenoceptor blockade by propranolol or their combination markedly reduced deriglidole-induced rise in insulin levels in a similar manner. Furthermore, in chlorisondamine-treated animals norepinephrine levels were strongly lowered and not modified by deriglidole and propranolol administration. However, in spite of sympathetic outflow and beta-adrenoceptor blockade, a moderate rise in insulinemia was still observed after deriglidole administration. Taken together these data demonstrate that deriglidole is the enantiomer that mediates the antihyperglycemic and insulin secretory effects of SL84.0418. Our study suggests that the major part of deriglidole effects is the consequence of the blockade of prejunctional alpha2-adrenoceptors that have reinforced the release of catecholamines in adrenergic nerve endings and indirectly activated postjunctional beta-adrenoceptors to further potentiate insulin secretion. However, it is also suggested that another undefined mechanism is involved in deriglidole potentiation of insulin secretion.     

Kinematics of the pelvic girdle and the thoracic and lumbar segments in the course of the lateral inclinations and rotations of the spine

Physiological displacements of the trunk are the addition of these of the pelvic girdle and thoracic and lumbar spine segments. For a long time (3), this conjunction had been noticed but without numbered precisions. The purpose of this communication is to appreciate quantitatively, from a series of 16 subjects, the respective share of each components during lateral bending movements in the frontal plan and movements of rotation in the transverse plan. It results from this work that the pelvic girdle presents as reduced amplitude (4 degrees) in lateral bending on the other hand, displacement predominate to the level of thoracic spine (50 degrees). In rotation pelvic displacements are very important (30 degrees), while the spine so thoracic that lumbar has a weak participation (inferior to 5 degrees). Moderated abduction of hips increases by significant manner the motility of the pelvic girdle.     

EMG power spectrum of respiratory and skeletal muscles during static contraction in healthy man

Changes in EMG power spectrum during isometric voluntary contraction maintained until exhaustion in the range of 20-80% MVC were studied in three skeletal muscles (adductor pollicis or AP, vastus lateralis, and medialis) and two respiratory muscles (diaphragm and rectus abdominis). Quantitative EMG analysis consisted of computation of the median frequency (MF) of power spectra and also the continuous measurement of EMG power in two bands of high (EH) and low (EL) frequencies using bandpass filters. This allowed the calculation of the H/L ratio and its time constant of decay rate (TC delta H/L) throughout the sustained static contraction. The main results were: (1) highly significant, positive correlations between TC delta H/L and the maximal MF changes and also the endurance time to fatigue; (2) EMG changes were determined early, within the first 10-20 s of contraction; and (3) EL always increased throughout the fatiguing isometric contraction, but EH changes markedly varied within the five muscle groups studied. These observations are discussed in terms of the differences in muscle fiber composition and also the variations in motor unit recruitment.     

Latest developments in GaN-based quantum devices for infrared optoelectronics

In this work, we summarize the latest progress in intersubband devices based on GaN/AlN nanostructures for operation in the near-infrared. We first discuss the growth and characterization of ultra-thin GaN/AlN quantum well and quantum dot superlattices by plasma-assisted molecular-beam epitaxy. Then, we present the performance of nitride-based infrared photodetectors and electro-optical modulators operating at 1.55 μm. Finally, we discuss the progress towards intersubband light emitters, including the first experimental observation of intersubband photoluminescence in nitride nanostructures.     

Tunable microcavity based on InP/air Bragg mirrors

A tunable Fabry–Perot filter based on InP/air Bragg mirrors has been studied. We have measured a resonance linewidth of 0.6 nm and a tuning range of 62 nm. The linewidth is kept below 1 nm over a 40 nm tuning range. The relation between the bending of the suspended layers during the actuation and the optical properties of the filter are analysed.     

Copolymerization with depropagation: Experiments and prediction of kinetics and properties of α-methylstyrene/methyl methacrylate copolymers. I. Solution copolymerization

α-Methylstyrene (α-MSt) and methyl methacrylate were copolymerized at 60°C in toluene by radical polymerization induced by azobisisobutyronitrile. The kinetics were followed by gravimetry and correlated with the molecular weights, microstructure, and glass transition temperature. A model was developed taking into account the equilibrium of the α-MSt homopolymerization that could not be neglected at 60°C and higher temperatures. The model is in good agreement with all the experimental data. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 65: 2297–2313, 1997     

Copolymerization with depropagation: Prediction of kinetics and properties of α‐methylstyrene–methyl methacrylate copolymers. II. Bulk copolymerization

In order to calculate some kinetic parameters, such as the reactivity ratios, of the system α‐methylstyrene–methyl methacrylate, the bulk copolymerization of these two monomers with azobis isobutironitrile (AIBN) as a radical initiator was studied. Experiments were performed at the various temperatures of 50, 60, and 80°C with 0.5 mol % of initiator (AIBN). The kinetics, molecular weights, microstructure, and glass transition temperature (T_g) of the copolymers were followed. A software, previously developed (part I), taking into account the equilibrium of the homopolymerization of α‐methylstyrene, was used to simulate the experimental data. The model was in good agreement with all the experimental data. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 72: 1611–1625, 1999     

How to increase the safety and efficacy of compounds against neurodegeneration? A multifunctional approach

Successful drug design requires not only the detailed knowledge of the pharmacokinetic and pharmacodynamic profiles of the drug candidate portfolio but also a thorough documentation of the possible toxic effects on humans and the environment. Thus, experimental and computational strategies able to measure or predict specific profiles of designed compounds related to their potential toxicity are highly desired. Moreover, a strategy to avoid toxic effects thus enhancing the potential efficacy of drug candidates is of great interest. To fulfil this aim, the pharmacochemistry research unit at the EPGL has recently developed and improved methodologies that detect the potential human health and environmental hazards of compounds active against neurodegeneration at an early stage. A three-step strategy is presented herein. In particular, i) an alternative index to model the bioconcentration of chemicals in the environment was determined; ii) the antioxidant activity of chemical species against free radicals was evaluated. Moreover, since antioxidants play a key role in both toxicity prevention and neuroprotection, iii) the potential interaction of such compounds with enzymatic targets involved in the neurodegenerative cascade was investigated in silico.