Naproxen and Cromolyn as New Glycogen Synthase Kinase 3β Inhibitors for Amelioration of Diabetes and Obesity: An Investigation by Docking Simulation and Subsequent In Vitro/In Vivo Biochemical Evaluation

Naproxen and cromolyn were investigated as new inhibitors of glycogen synthase kinase‐3β (GSK‐3β) in an attempt to explain their hypoglycemic properties. Study included simulated docking experiments, in vitro enzyme inhibition assay, and in vivo validations. Both drugs not only were optimally fitted within a GSK‐3β binding pocket via several attractive interactions with key amino acids but also exhibited potent in vitro enzymatic inhibitory activities of IC50 1.5 and 2.0 µM for naproxen and cromolyn, respectively. In vivo experiments illustrated that both drugs significantly reduced serum glucose and increased hepatic glycogen‐ and serum insulin levels in normal and type II diabetic Balb/c mice models. In obese animal model, both drugs exhibited significant reduction in mice weights, serum glucose, and resistin levels along with significant elevation in serum insulin, C‐peptide, and adiponectin values. It can be concluded that naproxen and cromolyn are novel GSK‐3β inhibitors and can help in management of diabetes and obesity. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:425–436, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21503     

Predicting muscle force generation during fast-starts for the common carp Cyprinus carpio

Muscle contractile properties have been characterised for white myotomal muscle from the common carp Cyprinus carpio at 10, 15, and 20 °C. The time course of muscle force development was measured when one, two, or three stimuli were delivered at the onset of constant velocity shortening. As the shortening velocity increased several parameters decreased including the maximum force, the time course for the contraction and the relative duration of the deactivation compared to the activation. The maximum force and the relative rates of activation to deactivation for the contraction were relatively independent of temperature, whereas the duration of the contraction decreased with increasing temperature. A predictive model was developed which was based on fitting a modified Weibull distribution to these observations. The model was used to interpolate the expected contractile forces during cyclic length-changes. Measured and predicted values for force and power during such cyclic work-loop experiments showed an excellent agreement over the range of shortening regimes typically found during swimming behaviours. However, the predicted force was overestimated during the deactivation phase of the contractions when the shortening velocities exceeded those found during swimming. Accepted: 25 May 1999     

Computational methods for the analysis of swimming biomechanics

A series of computer programs is presented which enables the analysis of fish body shape and mass distributions, spine positions, spine curvatures and coordinates for the centre of mass. Data are derived from silhouette outlines of swimming fish, white muscle strains during swimming, white muscle force-time development functions for body bending cycles, muscle force and power production along the whole fish body and hydrodynamic efficiencies for fast-start swimming behaviours.     

Phenolic compounds in date palm cultivars sensitive and resistant toFusarium oxysporum

In date palm (Phoenix dactylifera L.) leaves, the main compounds of the phenolic pool were quercetin and isorhamnetin heterosides, (+)-catechin and (-)-epicatechin. Although previously observed only in date palm fruits, 5-caffeoylshikimic acid (dactylifric acid) and its positional isomers (3-caffeoylshikimic acid and 4-caffeoylshikimic acid) were detected also in the leaves and roots. Quantitative, but not qualitative, differences between cultivars resistant and susceptible toFusarium oxysporum f. sp.albedinis during growth period were observed Acknowledgements: The authors are very grateful to Dr. Janati, Director of SCAS (INRA, Marrakech) for supplying the plant material used in this study. The study was funded by the Programme de Cooperation Franco-Marocaine (Al 473/90) between Cadi Ayyad University (Marrakech, Maroc) and Montpellier II University (France)     

Escape performance in the sub-Antarctic notothenioid fish Eleginops maclovinus

Fast-start performance associated with escape behaviour was investigated in the sub-Antarctic notothenioid Eleginops maclovinus from the Beagle Channel, Tierra del Fuego, Argentina (mean winter water temperature 4°C, mean summer water temperature 10°C). Fish acclimated to 8.5°C for 2 months were filmed at 2, 4, 6, 8 and 10°C. Escape responses were temperature dependent over the range of temperatures tested. Maximum length-specific velocity ([^(V)]_max )(\hat V_{\max } ) , maximum length-specific acceleration (Â_max) and inertial power output (P_iner) increased significantly with temperature. Q₁₀ values for [^(V)]_max\hat V_{\max } , Â_max and P_iner were 1.90, 3.27 and 8.90, respectively. Non-dimensional curvature of the spine ([^(c)])(\hat c) also varied significantly with temperature, but was higher at low temperatures. The values of [^(c)]\hat c were threefold lower than previously reported for Antarctic notothenioids and similar to the values for temperate species. The results indicate that the high values of [^(c)]\hat c observed during escape behaviour in Antarctic notothenioids are not a universal feature of the suborder. A greater flexion of the body during fast starts is therefore a promising candidate for a specialised feature of behaviour linked to low-temperature performance.