Combination of hyperoxia and a right-shifted HbO dissociation curve delays V̇o kinetics during maximal contractions in isolated muscle.

Acute enhancement of peripheral O diffusion may accelerate skeletal muscle O uptake (V̇o) kinetics and lessen fatigue during transitions from rest to maximal contractions. Surgically isolated canine gastrocnemius muscles in situ ( = 6) were studied during transitions from rest to 4 min of electrically stimulated isometric tetanic contractions at V̇o, in two conditions: normoxia (CTRL) and hyperoxia ([Formula: see text] = 1.00) + administration of a drug (RSR-13), which right shifts the Hb-O dissociation curve (Hyperoxia + RSR-13).

Disease activity return during natalizumab treatment interruption in patients with multiple sclerosis.

Background: Due to a heightened risk of progressive multifocal leukoencephalopathy (PML) with increased natalizumab exposure, some physicians interrupt treatment of patients with multiple sclerosis (MS) despite a lack of data regarding the safety of treatment interruption, the rate and severity of MS disease activity return after treatment interruption, or alternative treatment strategies.

Objectives: To determine the effects of natalizumab treatment interruption on clinical and MRI measures of disease activity in relapsing patients with MS.

Methods: Clinical relapses and gadolinium-enhanced (Gd+) lesions were analyzed over an 8-month period in patients from the AFFIRM, SENTINEL, and GLANCE studies of natalizumab, and their respective safety extension studies, following the voluntary suspension of natalizumab dosing that occurred in February 2005.

Sustained improvement in Expanded Disability Status Scale as a new efficacy measure of neurological change in multiple sclerosis: treatment effects with natalizumab in patients with relapsing multiple sclerosis.

Background: Validated measures of sustained improvements in neurological function have not been established for multiple sclerosis (MS) clinical studies.

Objective: To evaluate sustained Expanded Disability Status Scale (EDSS) change as a potential indicator of neurological improvement and as an outcome measure in MS clinical studies.

Methods: Analyses were performed on patients (n = 620) from the pivotal natalizumab study AFFIRM with baseline EDSS scores ≥2.

Regulation of dishevelled and beta-catenin in rat skeletal muscle: an alternative exercise-induced GSK-3beta signaling pathway.

beta-catenin is a multifunctional protein involved in cell-cell adhesion and the Wnt signaling pathway. beta-Catenin is activated upon its dephosphorylation, an event triggered by Dishevelled (Dvl)-mediated phosphorylation and deactivation of glycogen synthase kinase-3beta (GSK-3beta). In skeletal muscle, both insulin and exercise decrease GSK-3beta activity, and we tested the hypothesis that these two stimuli regulate beta-catenin.

Muscle-specific deletion of the Glut4 glucose transporter alters multiple regulatory steps in glycogen metabolism.

Mice with muscle-specific knockout of the Glut4 glucose transporter (muscle-G4KO) are insulin resistant and mildly diabetic. Here we show that despite markedly reduced glucose transport in muscle, muscle glycogen content in the fasted state is increased. We sought to determine the mechanism(s).