Effect of stimulation intensity on assessment of voluntary activation

Introduction: The interpolated twitch technique is often used to assess voluntary activation (VA) of skeletal muscles. We investigated VA and the voluntary torque-superimposed torque relationship using either supramaximal nerve stimulation or better tolerated submaximal muscle stimulation, which is often used with patients. Methods: Thirteen healthy subjects performed maximal and submaximal isometric knee extensions with superimposed maximal or submaximal doublets (100 Hz). Results: Superimposed torque relative to potentiated resting doublets was smaller with maximal nerve than with submaximal muscle stimulation. Maximal VA was 87 ± 7% and 93 ± 5% for submaximal muscle and maximal nerve stimulation, respectively. The individual voluntary torque-superimposed torque relationships were more linear for submaximal muscle stimulation, possibly leading to less overestimation of VA. Conclusions: Submaximal muscle stimulation can be used to estimate VA in the knee extensors. It is less painful, and overestimation of VA may be less compared with maximal nerve stimulation. © 2012 Wiley Periodicals, Inc

Tensin-3 is involved in osteogenic versus adipogenic fate of human bone marrow stromal cells

Background: The tightly controlled balance between osteogenic and adipogenic differentiation of human bone marrow-derived stromal cells (BMSCs) is critical to maintain bone homeostasis. Age-related osteoporosis is characterized by low bone mass with excessive infiltration of adipose tissue in the bone marrow compartment. The shift of BMSC differentiation from osteoblasts to adipocytes could result in bone loss and adiposity. Methods: TNS3 gene expression during osteogenic and adipogenic differentiation of BMSCs was evaluated by qPCR and Western blot analyses. Lentiviral-mediated knockdown or overexpression of TNS3 was used to assess its function. The organization of cytoskeleton was examined by immunofluorescent staining at multiple time points. The role of TNS3 and its domain function in osteogenic differentiation were evaluated by ALP activity, calcium assay, and Alizarin Red S staining. The expression of Rho-GTP was determined using the RhoA pull-down activation assay. Results:Loss of TNS3 impaired osteogenic differentiation of BMSCs but promoted adipogenic differentiation. Conversely, TNS3 overexpression hampered adipogenesis while enhancing osteogenesis. The expression level of TNS3 determined cell shape and cytoskeletal reorganization during osteogenic differentiation. TNS3 truncation experiments revealed that for optimal osteogenesis to occur, all domains proved essential. Pull-down and immunocytochemical experiments suggested that TNS3 mediates osteogenic differentiation through RhoA. Conclusions: Here, we identify TNS3 to be involved in BMSC fate decision. Our study links the domain structure in TNS3 to RhoA activity via actin dynamics and implicates an important role for TNS3 in regulating osteogenesis and adipogenesis from BMSCs. Furthermore, it supports the critical involvement of cytoskeletal reorganization in BMSC differentiation.</p

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Inhibition of insulin- and insulin-like growth factor-I-stimulated growth of human breast cancer cells by 1,25-dihydroxyvitamin D3 and the vitamin D3 analogue EB1089

1, 25 Dihydroxyvitamin D3 (1,25-(OH)2D3) and a number of synthetic vitamin D3 analogues with low calcaemic activity, have been shown to inhibit breast cancer cell growth in vitro as well as in vivo. The purpose of the present study was to investigate a possible interaction of 1, 25-(OH)2D3 and the vitamin D3 analogue EB1089 with the insulin-IGF-I regulatory system. The oestrogen receptor-positive MCF-7 human breast cancer cells used in this study are able to grow autonomously and their growth is stimulated by insulin. In order to avoid interference of IGF-binding proteins (IGF-BPs), we used an analogue of IGF-I, long R3 IGF-I, which stimulated MCF-7 cell growth similar to insulin. The growth stimulation by insulin and by long R3 IGF-I was completely inhibited by 1,25-(OH)2D3 and EB1089. Autonomous growth was also inhibited by 1,25-(OH)2D3 and EB1089. The analogue EB1089 was active at 50 times lower concentrations than 1,25-(OH)2D3. It was shown that growth inhibition was not achieved through downregulation of insulin and IGF-I binding after 48 h. Paradoxically, after prolonged treatment (8 days), an upregulation of insulin and IGF-I binding was observed. Two possible intracellular mediators of the insulin-IGF mitogenic signal are C-FOS and mitogen-activated protein (MAP) kinase. Insulin-induced C-FOS mRNA was inhibited by 1,25-(OH)2D3, suggesting that it could be involved in the growth inhibition by 1,25-(OH)2D3. MAP kinase activation appeared not to be involved in growth stimulation by both insulin and IGF-I. Together, the present study demonstrates that vitamin D3 compounds can block the mitogenic activity of insulin and IGF-I, which may contribute to their tumour suppressive activity observed in vivo. Copyrigh

Organic phosphate but not inorganic phosphate regulates Fgf23 expression through MAPK and TGF-ꞵ signaling

One of the main regulators of phosphate homeostasis is fibroblast growth factor 23 (FGF23), secreted by osteocytes. The effects of organic versus inorganic dietary phosphate on this homeostasis are unclear. This study used MC3T3-E1 FGF23-producing cells to examine the transcriptomic responses to these phosphates. Most importantly, the expression and secretion of FGF23 were only increased in response to organic phosphate. Gene ontology terms related to a response to environmental change were only enriched in cells treated with organic phosphate while cells treated with inorganic phosphate were enriched for terms associated with regulation of cellular phosphate metabolism. Inhibition of MAPK signaling diminished the response of Fgf23 to organic phosphate, suggesting it activates FGF23. TGF-β signaling inhibition increased Fgf23 expression after the addition of organic phosphate, while the negative TGF-β regulator Skil decreased this response. In summary, the observed differential response of FGF23-producing to phosphate types may have consequences for phosphate homeostasis.</p

Lack of effects between rupatadine 10 mg and placebo on actual driving performance of healthy volunteers

Introduction Rupatadine fumarate is a potent, selective, histamine H1-receptor antagonist and PAF inhibitor with demonstrated efficacy for the relief of allergic rhinitis. Rupatadine does not easily cross the blood–brain barrier and is believed to be non-sedating at therapeutic doses. Consequently, rupatadine should show no impairment on car driving. Objective This study compared the acute effects of rupatadine, relative to placebo and hydroxyzine (as an active control), on healthy subjects ’ driving performance

Рівняння електромагнітної механіки пористого насиченого середовища

За двоконтинуумного наближення отримано повну систему співвідношень моделі електромагнітомеханіки статистично однорідного та ізотропного пористого насиченого середовища. Враховано наявність подвійного електричного шару в околі межі контакту твердої і рідкої фаз.Complete set of the model equations for electromagnetic mechanics of the porous saturated medium being statistically homogeneous and isotropic is obtained in two-continuum approximation. The presence of a double electrical layer in an environ of contact boundary of solid and liquid phases is taken into account.В двухконтинуумном приближении получено полную систему соотношений модели электромагнитомеханики статистически однородной и изотропной пористой насыщенной среды. Учтено наличие двойного электрического слоя в окрестности границы контакта твердой и жидкой фаз