Le rimonabant ameliore le profit de risque cardio-metabolique chez le sujet obese ou en surpoids: synthese des etudes "RIO".

in Revue Médicale Suisse (2006), 2(76), 1916-23

RIO (Rimonabant In Obesity and related disorders) is a large phase 3 programme (>6600 patients) evaluating the efficacy and safety of rimonabant (5 or 20 mg/day), a CBI receptor antagonist of ... [more ▼]

RIO (Rimonabant In Obesity and related disorders) is a large phase 3 programme (>6600 patients) evaluating the efficacy and safety of rimonabant (5 or 20 mg/day), a CBI receptor antagonist of endocannabinoid system, in obese or overweight patients with or without comorbidities (RIO-Europe and RIO-North America), with untreated dyslipidaemia (RIO-Lipids) or with type 2 diabetes treated with metformin or sulfonylurea (RIO-Diabetes). Compared to placebo, rimonabant 20 mg/day consistently increases weight loss, reduces waist circumference, increases HDL cholesterol, lowers triglyceride levels, diminishes insulin resistance, and reduces the prevalence of metabolic syndrome. Almost half of the metabolic effects, including adiponectin increase, occur beyond weight loss, suggesting a direct peripheral effect of rimonabant. [less ▲]

Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial

in Lancet (2010), 376

BACKGROUND: Blockade of the endocannabinoid receptor reduces obesity and improves metabolic abnormalities such as triglycerides, HDL cholesterol, and fasting blood glucose. We assessed whether rimonabant ... [more ▼]

BACKGROUND: Blockade of the endocannabinoid receptor reduces obesity and improves metabolic abnormalities such as triglycerides, HDL cholesterol, and fasting blood glucose. We assessed whether rimonabant would improve major vascular event-free survival. METHODS: This double-blind, placebo-controlled trial was undertaken in 974 hospitals in 42 countries. 18,695 patients with previously manifest or increased risk of vascular disease were randomly assigned to receive either rimonabant 20 mg (n=9381) or matching placebo (n=9314). Randomisation was stratified by centre, implemented with an independent interactive voice response system, and all study personnel and participants were masked to group assignment. The primary endpoint was the composite of cardiovascular death, myocardial infarction, or stroke, as determined via central adjudication. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00263042. FINDINGS: At a mean follow-up of 13.8 months (95% CI 13.6-14.0), the trial was prematurely discontinued because of concerns by health regulatory authorities in three countries about suicide in individuals receiving rimonabant. All randomised participants were analysed. At the close of the trial (Nov 6, 2008), the composite primary endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 364 (3.9%) patients assigned to rimonabant and 375 (4.0%) assigned to placebo (hazard ratio 0.97, 95% CI 0.84-1.12, p=0.68). With rimonabant, gastrointestinal (3038 [33%] vs 2084 [22%]), neuropsychiatric (3028 [32%] vs 1989 [21%]), and serious psychiatric side-effects (232 [2.5%] vs 120 [1.3%]) were significantly increased compared with placebo. Four patients in the rimonabant group and one in the placebo group committed suicide. INTERPRETATION: The premature termination of this trial has important lessons for drug development. A drug that was being marketed for weight loss, but being tested for improving cardiovascular outcomes, induced a level of serious neuropsychiatric effects that was deemed unacceptable by regulatory authorities, and both the drug and the trial were abruptly terminated. [less ▲]

Rimonabant improves cardiometabolic risk factors in overweight/obese patients with poorly controlled type 2 diabetes (HbA(1c)>= 8%) on monotherapy with metformin or sulfonylureas

in Diabetologia (2006, September), 49(Suppl. 1), 483-484

Rimonabant improves health-related quality of life in overweight/obese patients with type 2 diabetes: RIO-diabetese study

in Value in Health (2006), 9(6, NOV-DEC), 327

Ring dike system to harness floodwater from the Mekong River for paddy rice cultivation in the Tonle Sap Lake floodplain in Cambodia

in Agricultural Water Management (2009), 96

Located in the floodplain of the Mekong River and the Tonle Sap River, Batheay irrigation system and its reservoir directly receive floodwater from the Mekong. The Batheay reservoir formedby a ring dike ... [more ▼]

Located in the floodplain of the Mekong River and the Tonle Sap River, Batheay irrigation system and its reservoir directly receive floodwater from the Mekong. The Batheay reservoir formedby a ring dike functions as botha reservoir anda paddy field. In thewet season, the ring dike prevents floodwater fromentering the reservoir and rainy season rice is growninside the dike. After harvesting, the gateson the ring dike are openedto receive floodwater. The water is stored inside the dike for cultivating dry season rice outside the dike. In this paper, the irrigation system is studied as a model site for future development of the floodplain of the Tonle Sap Lake of Cambodia. Specifically, this paper is concerned with the study of water balance and analysis of the hydrologic components of the Batheay irrigation system, and the effectiveness of the ring dike system. The study found that floodwater of the Mekong River contributed about 74% to the total inflow to the Batheay reservoir. Contributions to the total water supply of reservoir water, floodwater remaining in the fields, and precipitation were 73, 12, and 15%, respectively. The efficiency of the systemwas found to be 92%. The dike system is expected to be a paradigm for the floodplain of the Tonle Sap Lake. [less ▲]

Ring opening polymerization

in Kroschwitz, Jacqueline (Ed.) Encyclopedia of Polymer Science and Technology, Third Edition (2004)

Ring-opening metathesis polymerization of new alpha-norbornenyl poly(epsilon-caprolactone) macromonomers

in Journal of Polymer Science. Part A, Polymer Chemistry (1999), 37(14), 2447-2455

Poly(epsilon-caprolactone) (PCL) macromonomers capped by a polymerizable norbornene end-group have been synthesized and (co)polymerized by ring-opening metathesis with formation of graft copolymers and ... [more ▼]

Poly(epsilon-caprolactone) (PCL) macromonomers capped by a polymerizable norbornene end-group have been synthesized and (co)polymerized by ring-opening metathesis with formation of graft copolymers and polymacromonomers. -Norbornenyl PCL macromonomers have been synthesized by ring opening polymerization (ROP) of epsilon-caprolactone (CL) initiated by 2-diethylaluminoxymethyl-5-norbornene. Copolymerization of these PCL macromonomers with norbornene and polymerizable derivatives has been catalyzed by the [RuCl2(p-cymene)]2 PCy3/(trimethylsilyl)diazomethane complex yielding a series of poly(norbornene)-graft-poly(epsilon-caprolactone) copolymers. These new graft copolymers have been characterized by a set of analytical methods, i.e., SEC, 1H-NMR, FTIR, DSC, and TGA. Furthermore, PCL macromonomers have been polymerized into high molecular weight comb chains of narrow molecular weight distribution (Mw/Mn = 1.10) within high yields (90%). [less ▲]

Ring-Opening Polymerization of 1,4,8-Trioxaspiro[4.6]-9-undecanone: A new Route to Aliphatic Polyesters Bearing Functional Pendent Groups

in Macromolecules (1997), 30(3), 406-409

A straightforward and very efficient pathway has been reported for the synthesis of a functional derivative of ε-caprolactone, i.e. 5-ethylene ketal ε-caprolactone. This new monomer has been ... [more ▼]

A straightforward and very efficient pathway has been reported for the synthesis of a functional derivative of ε-caprolactone, i.e. 5-ethylene ketal ε-caprolactone. This new monomer has been homopolymerized and copolymerized with ε-caprolactone in a well-controlled manner, strongly suggesting absence of any side reactions. Deacetalization of the polyester chains is complete and reduction of the ketone groups into hydroxyl groups as well. No chain scission is observed to occur in the course of these two derivatization reactions. Thus, aliphatic polyesters bearing either ketone pendent groups or hydroxyl pendent groups can be easily prepared, which raises new application prospects. These materials proved to be easily redispersed in an aqueous medium. They form stable colloidal nanodispersions (e.g. 100 nm). These suspensions are stable more than 48 h at room temperature and may be viewed as potential drug colloidal vectors with a core−shell like structure. Different types of reactive groups on the surface of these nanoparticulate vectors are indeed available to the binding of species selected for molecular recognition and drug targeting. For instance, the well-known reactivity of ketones toward primary amines is a direct route to attach peptides onto biodegradable and biocompatible aliphatic polyesters. Poly(ε-caprolactone) with hydroxyl groups reactive toward triethylaluminum provides a macroinitiator for lactone and lactide polymerization, so that biodegradable and biocompatible functional comb, graft, and dendritic aliphatic polyesters can now be synthesized. [less ▲]

Ring-opening polymerization of alpha-chloro-epsilon-caprolactone and chemical modification of poly(alpha-chloro-epsilon-caprolactone) by atom transfer radical processes

in Macromolecules (2004), 37(11), 4055-4061

A highly versatile strategy was implemented in order to attach a range of polymer grafts and functional groups along the backbone of poly(epsilon-caprolactone). alpha-Chloro-epsilon-caprolactone ... [more ▼]

A highly versatile strategy was implemented in order to attach a range of polymer grafts and functional groups along the backbone of poly(epsilon-caprolactone). alpha-Chloro-epsilon-caprolactone (alphaClepsilonCL) was first prepared by the Baeyer-Villiger oxidation of alpha-chlorocyclohexanone. This monomer (alpha-Cl-epsilon-CL) was then copolymerized with epsilon-caprolactone in the presence of 2,2-dibutyl-2-stanna-1,3-dioxepane. Finally, the pendant activated chlorides of the copolymer were used to initiate (i) the "grafting from" of poly(methyl methacrylate) by atom transfer radical polymerization and (ii) the grafting of benzoate groups by atom transfer radical addition of 3-butenyl benzoate. [less ▲]

Ring-Opening Polymerization of γ-bromo-ε-caprolactone : A novel route to functionalized aliphatic polyesters

in Macromolecules (2000), 33(1), 14-18

The synthesis, characterization, and polymerization of a new cyclic ester, gamma-bromo-epsilon-caprolactone (gamma-BrCL), are reported. The ring-opening polymerization (ROP) of this new monomer initiated ... [more ▼]

The synthesis, characterization, and polymerization of a new cyclic ester, gamma-bromo-epsilon-caprolactone (gamma-BrCL), are reported. The ring-opening polymerization (ROP) of this new monomer initiated from Al((OPr)-Pr-i)(3) as initiator in toluene at 0 degrees C was found to be living and proceeds by a coordination-insertion mechanism. Random and block copolymerizations of this gamma-BrCL with epsilon-caprolactone (epsilon-CL) were also found to be living as evidenced by the experimental molecular weight which is consistent with that expected from the monomer to initiator molar ratio, the narrow polydispersity, and the good agreement between the comonomers molar fraction in the comonomer feed and the copolymer. The thermal transitions (Tg and Tm) in the epsilon-CL/gamma-Br-CL random copolymers depend strongly on the gamma-BrCL content. Increasing the gamma BrCL content in the copolymer [F(BrCL)] increased the Tg of the copolymer from -61 degrees C for poly(epsilon-caprolactone) to -16.5 degrees C for the poly( gamma-BrCL) homopolymer but decreased the Tm of the PCL to contents of similar to 30 mol % of gamma BrCL [F(BrCL) =0.3]Beyond this value, the copolymers were found to be amorphous and exist as viscous liquids. [less ▲]