Neuromuscular Consequences of an Extreme Mountain Ultra-Marathon

We investigated the physiological consequences of one of the most extreme exercises realized by humans in race conditions: a 166-km mountain ultra-marathon (MUM) with 9500 m of positive and negative elevation change. For this purpose, (i) the fatigue induced by the MUM and (ii) the recovery processes over two weeks were assessed. Evaluation of neuromuscular function (NMF) and blood markers of muscle damage and inflammation were performed before and immediately following (n = 22), and 2, 5, 9 and 16 days after the MUM (n = 11) in experienced ultra-marathon runners. Large maximal voluntary contraction decreases occurred after MUM (−35% [95% CI: −28 to −42%] and −39% [95% CI: −32 to −46%] for KE and PF, respectively), with alteration of maximal voluntary activation, mainly for KE (−19% [95% CI: −7 to −32%]). Significant modifications in markers of muscle damage and inflammation were observed after the MUM as suggested by the large changes in creatine kinase (from 144±94 to 13,633±12,626 UI L−1), myoglobin (from 32±22 to 1,432±1,209 µg L−1), and C-Reactive Protein (from <2.0 to 37.7±26.5 mg L−1). Moderate to large reductions in maximal compound muscle action potential amplitude, high-frequency doublet force, and low frequency fatigue (index of excitation-contraction coupling alteration) were also observed for both muscle groups. Sixteen days after MUM, NMF had returned to initial values, with most of the recovery process occurring within 9 days of the race. These findings suggest that the large alterations in NMF after an ultra-marathon race are multi-factorial, including failure of excitation-contraction coupling, which has never been described after prolonged running. It is also concluded that as early as two weeks after such an extreme running exercise, maximal force capacities have returned to baseline

The heparan sulfate sulfotransferase 3-OST3A (HS3ST3A) is a novel tumor regulator and a prognostic marker in breast cancer

International audienceHeparan sulfate (HS) proteoglycan chains are key components of the breast tumor microenvironment that critically influence the behavior of cancer cells. It is established that abnormal synthesis and processing of HS play a prominent role in tumorigenesis, albeit mechanisms remain mostly obscure. HS function is mainly controlled by sulfotransferases, and here we report a novel cellular and pathophysiological significance for the 3-O-sulfotransferase 3-OST3A (HS3ST3A), catalyzing the final maturation step of HS, in breast cancer. We show that 3-OST3A is epigenetically repressed in all breast cancer cell lines of a panel representative of distinct molecular subgroups, except in human epidermal growth factor receptor 2-positive (HER2+) sloan-kettering breast cancer (SKBR3) cells. Epigenetic mechanisms involved both DNA methylation and histone modifications, producing different repressive chromatin environments depending on the cell molecular signature. Gain and loss of function experiments by cDNA and siRNA transfection revealed profound effects of 3-OST3A expression on cell behavior including apoptosis, proliferation, response to trastuzumab in vitro and tumor growth in xenografted mice. 3-OST3A exerted dual activities acting as tumor-suppressor in lumA-michigan cancer foundation (MCF)-7 and triple negative-MD Anderson (MDA) metastatic breast (MB)-231 cells, or as an oncogenic factor in HER2+-SKBR3 cells. Mechanistically, fluorescence-resonance energy transfer-fluorescence-lifetime imaging microscopy experiments indicated that the effects of 3-OST3A in MCF-7 cells were mediated by altered interactions between HS and fibroblast growth factor-7 (FGF-7). Further, this interplay between HS and FGF-7 modulated downstream ERK, AKT and p38 cascades, suggesting that altering 3-O-sulfation affects FGFR2IIIb-mediated signaling. Corroborating our cellular data, a clinical study conducted in a cohort of breast cancer patients uncovered that, in HER2+ patients, high level expression of 3-OST3A in tumors was associated with reduced relapse-free survival. Our findings define 3-OST3A as a novel regulator of breast cancer pathogenicity, displaying tumor-suppressive or oncogenic activities in a cell-and tumor-dependent context, and demonstrate the clinical value of the HS-O-sulfotransferase 3-OST3A as a prognostic marker in HER2+ patients

Vitamin and mineral supplementation and neuromuscular recovery after a running race

PURPOSE: This double-blind study investigated the effects of vitamin and mineral complex supplementation on the neuromuscular function of the knee-extensor muscles after a prolonged trail running race. METHODS: Twenty-two well-trained endurance runners took either placebo (Pl group) or vitamins and minerals (Vm group) for 21 d before the race and for 2 d after the race. Maximal voluntary contractions (MVC) and surface EMG activity of the vastus lateralis (VL) muscle were recorded before (pre) and 1 h (post), 24 h (post 24) and 48 h (post 48) after the race. Central activation ratio (CAR), neural (M-wave), and contractile (muscular twitch) properties of the quadriceps muscles were analyzed using electrical stimulation techniques. RESULTS: The knee-extensor MVC was significantly (P < 0.01) reduced after exercise for both groups (Vm: 36.5 +/- 3.0 \%; Pl: 36.9 +/- 2.1\%), but MVC recovery was greater for Vm than Pl after 48 h (11\%, P < 0.05). The reduced MVC after exercise was associated with a significant reduction in maximal EMG normalized to the M-wave in VL muscle and in CAR for both groups. Characteristics of the muscular twitch were not significantly altered for either groups, whereas M-wave duration increased significantly (P < 0.05) after exercise. CONCLUSIONS: The reduction of MVC immediately after the race appeared to result from peripheral mechanisms such as a failure in muscle membrane excitation and, to a lesser extent, from reduced central activation. The cause of the depressed MVC 24 h after the race seemed to be located within the muscle itself. A dietary supplementation of a vitamin and mineral complex does not attenuate the loss of contractile function immediately after the running exercise, and it may accelerate the recovery of maximal force capacity

Vitamin and mineral supplementation and neuromuscular recovery after a running race

This double-blind study investigated the effects of vitamin and mineral complex supplementation on the neuromuscular function of the knee-extensor muscles after a prolonged trail running race