ABSTRACT
The main objectives of this study were to examine which testing protocol (one/two/three trials) and method (best/average value) used for determining maximal handgrip strength is more reliable for individuals with intellectual disabilities (ID) and to compare the reliability and variability of maximal handgrip strength measurement between individuals with ID and healthy individuals. Twenty individuals with ID (18.7±3.3 years) and 20 healthy individuals (18.5±3.4 years) performed six separate sessions. During these sessions, the participants' maximal handgrip strength was evaluated using three protocols with different number of trials (one/two/three). In individuals with ID, the protocols with one and two trials were less reliable (ICC=0.78-0.95; SEM%=9-21) than the protocol with three trials (ICC=0.94-0.96; SEM%=8-10) whereas in healthy individuals all protocols were equally reliable (ICC=0.95-0.99; SEM%=1.9-4.9). In individuals with ID, the mean of three trials (ICC=0.96, SEM=1.19-1.35kg, SEM%=8.2-8.7) had slightly higher reliability than the best of three trials (ICC=0.94, SEM=1.47-1.75kg, SEM%=9.2-10.1). Furthermore, the variability of maximal handgrip strength measurement was about twofold higher in individuals with ID (CV=37-45%) vs. healthy individuals (CV=21-23%). Maximal handgrip strength can be measured reliably in young individuals with ID using the mean of three trials as the most reliable approach for the determination of maximal handgrip strength.
Subject(s)
Hand Strength , Intellectual Disability , Health Status , Humans , Reproducibility of ResultsABSTRACT
Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulus, the expression of which increases in skeletal muscle after exercise. Because exercise is also accompanied by increased intramuscular reactive oxygen species (ROS) generation, we tested the hypothesis that ROS stimulate VEGF production from skeletal myotubes. Differentiated C(2)C(12) skeletal myotubes exposed to ROS-producing agents exhibited a concentration-dependent increase in VEGF production, whereas undifferentiated myoblasts did not respond to oxidants. Moreover, conditioned medium from ROS-treated myotubes increased the bovine lung microvascular cell proliferation rate. To study the mechanism(s) involved in the stimulation of VEGF production by ROS, myotubes were pretreated with a selective phosphatidylinositol 3-kinase (PI3K) inhibitor, LY-294002, before being exposed to hydrogen peroxide or pyrogallol. LY-294002 attenuated both Akt phosphorylation and VEGF production. In addition, oxidants increased nuclear factor-kappaB-dependent promoter activity in transiently transfected myotubes; however, pretreatment with the pharmacological inhibitor of nuclear factor-kappaB, diethyldithiocarbamate, did not affect the oxidant-stimulated VEGF release. We conclude that ROS induce VEGF release from myotubes via a PI3K/Akt-dependent pathway.
Subject(s)
Endothelial Growth Factors/biosynthesis , Lymphokines/biosynthesis , Muscle, Skeletal/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Protein Serine-Threonine Kinases , Reactive Oxygen Species/metabolism , Animals , Cattle , Cell Division/drug effects , Cells, Cultured , Culture Media, Conditioned/pharmacology , Endothelium, Vascular/cytology , Mice , Microcirculation , Muscle, Skeletal/cytology , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-akt , Pulmonary Circulation , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth FactorsABSTRACT
Flavonoids are naturally occurring polyphenolic compounds with a wide distribution throughout the plant kingdom. In the present study, we compared the ability of several flavonoids to modulate the production of proinflammatory molecules from lipopolysaccharide (LPS)-stimulated macrophages and investigated their mechanism(s) of action. Pretreatment of RAW 264.7 with luteolin, luteolin-7-glucoside, quercetin, and the isoflavonoid genistein inhibited both the LPS-stimulated TNF-alpha and interleukin-6 release, whereas eriodictyol and hesperetin only inhibited TNF-alpha release. From the compounds tested luteolin and quercetin were the most potent in inhibiting cytokine production with an IC(50) of less than 1 and 5 microM for TNF-alpha release, respectively. To determine the mechanisms by which flavonoids inhibit LPS signaling, we used luteolin and determined its ability to interfere with total protein tyrosine phosphorylation as well as Akt phosphorylation and nuclear factor-kappaB activation. Pretreatment of the cells with luteolin attenuated LPS-induced tyrosine phosphorylation of many discrete proteins. Moreover, luteolin inhibited LPS-induced phosphorylation of Akt. Treatment of macrophages with LPS resulted in increased IkappaB-alpha phosphorylation and reduced the levels of IkappaB-alpha. Pretreatment of cells with luteolin abolished the effects of LPS on IkappaB-alpha. To determine the functional relevance of the phosphorylation events observed with IkappaB-alpha, macrophages were transfected either with a control vector or a vector coding for the luciferase reporter gene under the control of kappaB cis-acting elements. Incubation of transfected RAW 264.7 cells with LPS increased luciferase activity in a luteolin-sensitive manner. We conclude that luteolin inhibits protein tyrosine phosphorylation, nuclear factor-kappaB-mediated gene expression and proinflammatory cytokine production in murine macrophages.
