Showing papers by "Solvay published in 2010"

Testosterone concentrations in diabetic and nondiabetic obese men.

Abstract: Objective: To determine the prevalence of subnormal testosterone concentrations in patients with obesity and with type 2 diabetes in a primary care clinic population. Research Design and Methods: FT concentrations of 1849 men(1451 non-diabetic and 398 diabetic) in the Hypogonadism In Males(HIM) study were analyzed. HIM study was a US based cross-sectional study designed to define the prevalence of hypogonadism in men older than 45 years. FT was measured by equilibrium dialysis. Results: Prevalence of subnormal FT concentrations in lean, overweight and obese non-diabetic men was 26%(n=275), 29%(n=687) and 40%(n=489) respectively(p Conclusion: 40% of obese non-diabetic and 50% of obese diabetic men above the age of 45 years have subnormal FT concentrations. In view of its high prevalence, obesity is probably the condition most frequently associated with subnormal FT concentration in males. The concomitant presence of diabetes is associated with an additional increase in prevalence of subnormal FT concentration.

Kinetics of electrocatalytic reduction of oxygen and hydrogen peroxide on dispersed gold nanoparticles

Abstract: The electrocatalytic properties of Au nanoparticles of mean size between 4.2 to 9.5 nm have been investigated for the oxygen reduction reaction (ORR). The particles were prepared on dispersed Vulcan XC-72R carbon black by reduction of a gold salt and by deposition of polymer stabilised gold sols. These were then attached to a glassy carbon disc electrode from their dispersion in a Nafion® solution. The dependence on particle size of activity and selectivity for H2O2 formation and the rate constants for oxygen and hydrogen peroxide reduction have been investigated using Rotating (Ring) Disc Electrode measurements. The electrocatalytic activity showed a maximum for a mean particle size of 5.7 nm and decreased significantly with particle size. The number of electrons exchanged per O2 molecule increased from a value close to 2 to 3.4 as the potential was made more negative. The oxygen reduction selectivity for H2O2 production was higher for mean particle sizes below 6 nm.

High temperature operation of a solid polymer electrolyte fuel cell stack based on a new ionomer membrane

Abstract: Polymer electrolyte fuel cell stacks assembled with Johnson Matthey Fuel Cells and SolviCore MEAs based on the Aquivion™ E79-03S short-side chain (SSC), chemically stabilised perfluorosulphonic acid membrane developed by Solvay Solexis were investigated at CNR-ITAE in the EU Sixth Framework ‘Autobrane' project. Electrochemical experiments in fuel cell short stacks were performed under practical automotive operating conditions at pressures of 1–1.5 bar abs. over a wide temperature range, up to 130 °C, with varying levels of humidity (down to 18% R. H.). The stacks using large area (360 cm2) MEAs showed elevated performance in the temperature range from ambient to 100 °C (cell power density in the range of 600–700 mWcm–2) with a moderate decrease above 100 °C. The performances and electrical efficiencies achieved at 110 °C (cell power density of about 400 mWcm–2 at an average cell voltage of about 0.5–0.6 V) are promising for automotive applications. Duty-cycle and steady-state galvanostatic experiments showed excellent stack stability for operation at high temperature. A performance comparison of AquivionTM and NafionTM-based MEAs under practical operating conditions showed a significantly better capability for the Solvay Solexis membrane to sustain high temperature operation.

Irreversible nanogel formation in surfactant solutions by microporous flow

Abstract: Viscoelastic gels can be made by using flow to induce structure into solutions containing surfactant micelles. However, the gels disintegrate soon after flow stoppage. By using a microfluidic-assisted laminar-flow process to generate very high extension rates, it is now shown that permanent gels can be made, creating new opportunities for applications.

2009 White Paper on Recent Issues in Regulated Bioanalysis from The 3rd Calibration and Validation Group Workshop

Abstract: The 3rd Calibration and Validation Group Workshop on Recent Issues in Regulated Bioana lysis was organized by the Calibration and Validation Group as a 1.5-day full immersion workshop for contract research organizations, pharmaceutical companies and regulatory agencies to discuss several ‘hot’ topics concerning bioanalytical issues and regulatory challenges. A consensus was reached among panelists and attendees on many points regarding method validation of small molecules.

Toward a consensus model of the hERG potassium channel.

Abstract: Malfunction of hERG potassium channels, due to inherited mutations or inhibition by drugs, can cause long QT syndrome, which can lead to life-threatening arrhythmias. A three-dimensional structure of hERG is a prerequisite to understand the molecular basis of hERG malfunction. To achieve a consensus model, we carried out an extensive analysis of hERG models based on various alignments of helix S5. We analyzed seven models using a combination of conventional geometry/packing/normality validation methods as well as molecular dynamics simulations and molecular docking. A synthetic test set with the X-ray crystal structure of K(v)1.2 with artificially shifted S5 sequences modeled into the structure served as a reference case. We docked the known hERG inhibitors (+)-cisapride, (S)-terfenadine, and MK-499 into the hERG models and simulation snapshots. None of the single analyses unambiguously identified a preferred model, but the combination of all three revealed that there is only one model that fulfils all quality criteria. This model is confirmed by a recent mutation scanning experiment (P. Ju, G. Pages, R. P. Riek, P. C. Chen, A. M. Torres, P. S. Bansal, S. Kuyucak, P. W. Kuchel, J. I. Vandenberg, J. Biol. Chem. 2009, 284, 1000-1008). We expect the modeled structure to be useful as a basis both for computational studies of channel function and kinetics as well as the design of experiments.

Effect of Particles on the Flow-Induced Crystallization of Polypropylene at Processing Speeds

Abstract: The effect of particles with different diameters on flow-induced crystallization from low shear rates to processing speeds is studied using mixtures of polypropylene and zinc oxide with diameters between 35 nm and 1 μm. The nucleating efficiency of the particles was characterized by means of the Lotz efficiency scale using DSC. Flow-induced crystallization at processing speeds was studied by means of the birefringence and transmitted intensity measurements using a specially designed sliding-plate flow cell. For crystallization under quiescent conditions and after shear steps at low shear rates, there are significant differences between the kinetics of the neat polymer, the mixture with the 1 μm zinc oxide, and the mixtures with the midrange particles, which are in agreement with the nucleating efficiency of the particles. As the shear rate is increased, the crystallization kinetics of the mixtures and neat polymer become similar, independent of particle diameter. The transition to highly oriented shish-ke...

Design, synthesis, biological properties, and molecular modeling investigations of novel tacrine derivatives with a combination of acetylcholinesterase inhibition and cannabinoid CB1 receptor antagonism.

Abstract: Pyrazolines 7−10 were designed as novel CB1 receptor antagonists, which exhibited improved turbidimetric aqueous solubilities. On the basis of their extended CB1 antagonist pharmacophore, hybrid molecules exhibiting cannabinoid CB1 receptor antagonistic as well as acetylcholinesterase (AChE) inhibiting activities were designed. The target compounds 12, 13, 20, and 21 are based on 1 (tacrine) as the AChE inhibitor (AChEI) pharmacophore and two different CB1 antagonistic pharmacophores. The imidazole-based 20 showed high CB1 receptor affinity (48 nM) in combination with high CB1/CB2 receptor subtype selectivity (>20-fold) and elicited equipotent AChE inhibitory activity as 1. Molecular modeling studies revealed the presence of a binding pocket in the AChE enzyme which nicely accommodates the CB1 pharmacophores of the target compounds 12, 13, 20, and 21.

3D Seiberg-like dualities and M2 branes

Abstract: We investigate features of duality in three dimensional $ \mathcal{N} = 2 $ Chern-Simons matter theories conjectured to describe M2 branes at toric Calabi Yau four-fold singularities. For 3D theories with non-chiral 4D parents we propone a Seiberg-like duality which turns out to be a toric duality. For theories with chiral 4D parents we discuss the conditions under which that Seiberg-like duality leads to toric duality. We comment on such duality in 3D theories without 4D parents.

Lithium sulfur battery

Abstract: A lithium sulfur battery comprising at least one fluorosubstituted compound is described. Preferred fluorosubstituted compounds which are predominantly solvents are notably selected from the group consisting of fluorosubstituted carboxylic acid esters, fluorosubstituted carboxylic acid amides, fluorosubstituted fluorinated ethers, fluorosubstituted carbamates, fluorosubstituted cyclic carbonates, and fluorosubstituted acyclic carbonates fluorosubstituted ethers, perfluoroalkyl phosphoranes, fluorosubstituted phosphites, fluorosubstituted phosphates, fluorosubstituted phosphonates and fluorosubstituted heterocycles. Monofluoroethylene carbonate, cis-difluoroethylene carbonate, trans- difluoroethylene carbonate, 4,4- difluoroethylene carbonate, trifluoroethylene carbonate, tetrafluoroethylene carbonate, 4-fluoro-4-methyl-l,3-dioxolane-2-one, 4-fluoro-4-ethyl- 1,3-dioxolane-2-one, 2,2,2-trifluoroethyl-methyl carbonate, 2,2,2-trifluoroethyl-fluoromethyl carbonate are preferred. The solvent my further comprise non-fluorinated solvents, e.g. ethylene carbonate, a dialkyl carbonate or propylene carbonate. The invention also concerns the use of fluorinated compounds as additive for such batteries and specific electrolyte solutions.

Reducing uncertainty in value-based pricing using evidence development agreements

Abstract: Value-based pricing (VBP), whereby prices are set according to the perceived benefits offered to the consumer at a time when costs and benefits are characterized by considerable uncertainty and are then reviewed ex post, is a much discussed topic in pharmaceutical reimbursement. It is usually combined with coverage with evidence development (CED), a tool in which manufacturers are granted temporary reimbursement but are required to collect and submit additional health economic data at review. Many countries, including the UK, are signalling shifts in this direction. Several countries, including Sweden, have already adopted this approach and offer good insight into the benefits and pitfalls in actual practice. To describe VBP reimbursement decision making using CED in actual practice in Sweden. Decision making by The Dental and Pharmaceutical Benefits Agency (TLV) in Sweden was reviewed using a case study of continuous intraduodenal infusion of levodopa/carbidopa (Duodopa®) in the treatment of advanced Parkinson’s disease (PD) with severe motor fluctuations. The manufacturer of Duodopa® applied for reimbursement in late 2003. While the proper economic data were not included in the submission, TLV granted reimbursement until early 2005 to provide time for the manufacturer to submit a formal economic evaluation. The re-submission with economic data was considered inadequate to judge cost effectiveness, so TLV granted an additional extension of reimbursement until August 2007, at which time conclusive data were expected. The manufacturer initiated a 3-year, prospective health economic study and a formal economic model. Data from a pre-planned interim analysis of the data were loaded into the model and the cost-effectiveness ratio was the basis of the next re-submission. TLV concluded that the data were suitable for making a definite decision and that the drug was not cost effective, deciding to discontinue reimbursement for any new patients (current patients were unaffected). The manufacturer continued to collect data and to improve the economic model and re-submitted in 2008. New data and the improved model resulted in reduced uncertainty and a lower cost-effectiveness ratio in the range of Swedish kronor (SEK)430 000 per QALY gained in the base-case analysis, ranging up to SEK900 000 in the most conservative sensitivity analysis, resulting in reimbursement being granted. The case of Duodopa® provides excellent insight into VBP reimbursement decision making in combination with CED and ex post review in actual practice. Publicly available decisions document the rigorous, time-consuming process (four iterations were required before a final decision could be reached). The data generated as part of the risk-sharing agreement proved correct the initial decision to grant limited coverage despite lack of economic data. Access was provided to 100 patients while evidence was generated. Economic appraisal differs from clinical assessment, and decision makers benefit from analysis of naturalistic, actual practice data. Despite reviewing the initial trial-based, ‘piggy-back’ economic analysis, TLV was uncertain of the cost effectiveness in actual practice and deferred a final decision until observational data from the DAPHNE study became available. Second, acceptance of economic modelling and use of temporary reimbursement conditional on additional evidence development provide a mechanism for risk sharing between TLV and manufacturers, which enabled patient access to a drug with proven clinical benefit while necessary evidence to support claims of cost effectiveness could be generated.

Degradation Reactions in Anthraquinone Process of Hydrogen Peroxide Synthesis

Abstract: Present research concentrates on the process of anthraquinone degradation in the course of hydrogenation carried out in the presence of palladium catalyst. Hydrogenation experiments were carried out using agitated glass laboratory batch type reactor at atmospheric pressure of hydrogen and temperature of 55 °C. Catalytic tests were performed using solutions composed of 2-ethyl-9,10-anthraquinone (eAQ) and a mixture of eAQ and 2-ethyloxanthrone (OXO) with various proportions. Degradation of anthraquinone was studied and in particular, the role of reduced forms of quinone namely hydroquinone and its tautomer OXO is discussed. A difference in the course of reactions pathways: hydrogenation of aromatic rings to give 2-ethyl-5,6,7,8-tetrahydro-9,10-anthraquinone (active quinone) and hydrogenolysis reactions yielding degradation products was observed. Present research concentrates on the process of 2-ethyl-9,10-anthraquinone degradation on palladium catalyst. The role of reduced forms, hydroquinone-enol form and its keto-tautomer is discussed.

Organic electronic devices and polymers, including photovoltaic cells and diketone-based polymers

Abstract: Polymers which can be used in p-type materials for organic electronic devices and photovoltaic cells. Compounds, monomers, dimers, trimers, and polymers comprising formula (I); Good photovoltaic efficiency and lifetime can be achieved. The R group can provide solubility, environmental stability, and fine tuning of spectroscopic and/or electronic properties. Different polymer microstructures can be prepared which encourage multiple band gaps and broad and strong absorptions. The carbonyl can interact with adjacent thiophene rings to provide backbone with rigidity, induce planarity, and reduce and/or eliminate intramolecular chain twisting defects. Polymers comprising benzodithiophene and/or benzothiadiazole structures can show particularly high performance.

Asymmetric hydrogenation with highly active IndolPhos-Rh catalysts: kinetics and reaction mechanism.

Abstract: The mechanism of the Indol- Phos–Rh-catalyzed asymmetric hydrogenation of prochiral olefins has been investigated by means of X-ray crystal structure determination, kinetic measurements, high-pressure NMR spectroscopy, and DFT calculations. The mechanistic study indicates that the reaction follows an unsaturate/dihydride mechanism according to Michaelis– Menten kinetics. A large value of KM (KM=5.01 0.16m) is obtained, which indicates that the Rh–solvate complex is the catalyst resting state, which has been observed by high-pressure NMR spectroscopy. DFT calculations on the substrate–catalyst complexes, which are undetectable by experimental means, suggest that the major substrate–catalyst complex leads to the product. Such a mechanism is in accordance with previous studies on the mechanism of asymmetric hydrogenation reactions with C1-symmetric heteroditopic and monodentate ligands.

Double-blind study of pardoprunox, a new partial dopamine agonist, in early Parkinson's disease†

Abstract: This study examined the efficacy and safety of the partial dopamine agonist, pardoprunox (SLV308), in the treatment of patients with early Parkinson's disease (PD). Patients were randomized to receive pardoprunox (n = 69) or placebo (n = 70). Pardoprunox was titrated to each patient's optimal dose (9–45 mg/d) over 2 to 6 weeks and then maintained at this dose for a further 3 weeks. Concomitant anti-Parkinson treatment was not permitted. In the primary analysis, Unified PD Rating Scale (UPDRS)-Motor score was improved in pardoprunox-treated patients (overall mean dose 23.8 mg/d; −7.3 points), as compared with placebo (−3.0 points; P = 0.0001), from baseline to end point. At end point, there were more responders (≥30% reduction in UPDRS-Motor score) in the pardoprunox group (50.7%) than in the placebo group (15.7%; P < 0.0001). In other secondary analyses, UPDRS-activities of daily living (ADL) and -ADL+Motor scores were also significantly more improved in the pardoprunox group. Nausea was reported by 32 of 68 (47.1%) pardoprunox-treated patients (vs. 3/70, 4.3%, placebo-treated patients), with dizziness, somnolence, headache, and asthenia also reported by ≥10 patients. In this exploratory proof-of-concept study, pardoprunox significantly improved motor function in patients with early PD. The efficacy and safety profile of pardoprunox justifies its further investigation in PD. © 2010 Movement Disorder Society

A Very High Prevalence of Low HDL Cholesterol in Spanish Patients With Acute Coronary Syndromes

Abstract: Background Total and low-density lipoprotein cholesterol (LDL-C) concentrations in coronary artery disease have progressively declined, although high-density lipoprotein cholesterol (HDL-C) has not always been evaluated. The prevalence and related factors of low HDL-C in a cohort of Spanish patients with acute coronary syndromes (ACS) were assessed. Methods Clinical and laboratory data registered at admission and at discharge of 648 patients admitted to coronary care units of 6 Spanish hospitals for ACS between January 2004 and September 2007 were analyzed. Results Low HDL-C (HDL-C < 1.04 mmol/L) was observed in 367 (56.6%) patients. Male gender, smoking, hypertension, diabetes, high body mass index, and triglycerides were related to low HDL-C. Female gender was the strongest protective factor against low HDL-C (0.619; 95% confidence interval [CI]: 0.410–0.934; P = 0.022), whereas high triglycerides (1.653; 95% CI: 1.323–2.064; P < 0.001) followed by previous ischemic disease (1.504; 95% CI: 1.073–2.110; P = 0.018) were the strongest factors associated with low HDL-C. One-third of patients were taking statins at admission, but only 2% were on fibrate therapy. A large increase in statin therapy, but not in other hypolipemiant drug therapy, between admission and discharge was noted in the whole cohort and among patients with low HDL-C. Conclusion Spanish patients with ACS have a very high prevalence of low HDL-C. Male gender, high triglycerides, and previous ischemic disease are strong, independent factors associated with this disorder. As low HDL-C remains almost completely untreated in ACS, strategies to enhance the treatment of this lipoprotein abnormality are urgently required. Copyright © 2010 Wiley Periodicals, Inc.

Solid support synthesis of a PNA‐DNA hybrid

Abstract: The solid support synthesis of a homothymine PNA-DNA octamer (i.e. hybrid 13) could be realized using tetrabutylammonium N-(2-(4-methoxytrityl)-aminoethyl)-N-((thymin-1-yl)acetyl)glycinate as PNA building block and the respective 2-cyanoethyl-N,N-diisopropylphosphoramidite derivatives of both 5′-O-(4,4′-dimethoxytrityl)thymidine and 5′-N-(4-methoxytrityl)amino-5′-deoxythymidine.

Cerebral blood volume alterations in the perilesional areas in the rat brain after traumatic brain injury—comparison with behavioral outcome

Abstract: In the traumatic brain injury (TBI) the initial impact causes both primary injury, and launches secondary injury cascades. One consequence, and a factor that may contribute to these secondary changes and functional outcome, is altered hemodynamics. The relative cerebral blood volume (CBV) changes in rat brain after severe controlled cortical impact injury were characterized to assess their interrelations with motor function impairment. Magnetic resonance imaging (MRI) was performed 1, 2, 4 h, and 1, 2, 3, 4, 7, and 14 days after TBI to quantify CBV and water diffusion. Neuroscore test was conducted before, and 2, 7, and 14 days after the TBI. We found distinct temporal profile of CBV in the perilesional area, hippocampus, and in the primary lesion. In all regions, the first response was drop of CBV. Perifocal CBV was reduced for over 4 days thereafter gradually recovering. After the initial drop, the hippocampal CBV was increased for 2 weeks. Neuroscore demonstrated severely impaired motor functions 2 days after injury (33% decrease), which then slowly recovered in 2 weeks. This recovery parallelled the recovery of perifocal CBV. CBV MRI can detect cerebrovascular pathophysiology after TBI in the vulnerable perilesional area, which seems to potentially associate with time course of sensory-motor deficit.