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This study applied EMG analysis methods to identify muscle group activity profiles and potential overload risks in powered wheelchair use.We quantified muscle effort and fatigue using EMG analysis methods during powered wheelchair manoeuvres by 10 multiple sclerosis patients. Video recordings of the different sub-tasks were related to information on surface EMG amplitude (rectified EMG) and spectral information (Median frequency) from M. trapezius, M. deltoideus (pars medius), M. deltoideus (pars anterior), M. pectoralis, M. biceps, M. triceps, wrist extensors and flexors, using Joint Analysis of EMG Spectrum and Amplitude (JASA analysis).Task durations and subjective data indicated that tasks requiring finer motor control took longer and were perceived as more difficult. Kinesiological functions of all muscle groups identified forward steering to be associated with activation of M. deltoideus (pars anterior), M. pectoralis, M. trapezius and M. deltoideus (pars medius); backwards steering with predominant activation of M. deltoideus (pars medius), M. biceps brachii and wrist flexors; left steering with maximal activation of M. biceps and wrist flexors, and right steering with maximal activation of M. triceps and wrist extensors. These profiles were confirmed in analysis of the functional tasks. JASA analysis documented muscle fatigue in the wrist extensors, whereas increased activation was found in M. trapezius, M. deltoideus (pars anterior) and wrist flexors.EMG based kinesiological analysis gives insight in muscle activity and fatigue during powered wheelchair manoeuvres.

While the harmful effects of alcohol abuse are well documented, experimental and clinical data support a potential benefit of light to moderate alcohol consumption. Cross-sectional studies have suggested an association between alcohol consumption and multiple sclerosis (MS) disability. In the absence of prospective, longitudinal studies, the causal nature of this relationship cannot be established. It remains possible that patients with increased disability progression reduce their alcohol intake. Even though there is substantial evidence for anti-inflammatory effects of low-to-moderate doses of alcohol, the associations need to be interpreted very cautiously. This study discusses the current state of knowledge about MS and alcohol consumption, and the limitations in conducting research with retrospective data in patients with MS.

Long-term exposure to ethanol leads to an imbalance in different excitatory and inhibitory amino acids. When ethanol consumption is reduced or completely stopped, these imbalances in different amino acids and neurotransmitters are behaviorally expressed in the form of ethanol withdrawal. Glutamate, a major excitatory amino acid, and GABA, a major inhibitory amino acid, are responsible, at least partly, for ethanol withdrawal symptoms. The hypofunction of GABAA receptors and enhanced function of NMDA receptors are suggested to be responsible for the increase in the behavioral susceptibility during ethanol withdrawal. This imbalance between receptors may be exacerbated by repeated withdrawal. Because multiple and repeated periods of chronic ethanol consumption and withdrawal often occur in alcohol abusers, animal studies on the neurochemical changes in different amino acids following chronic ethanol treatment (CET) that is interrupted by repeated ethanol withdrawal episodes may be of clinical relevance for the development of treatment strategies. Brain glutamate increases during the first cycle of ethanol withdrawal, and this increase is much higher during the third cycle of ethanol withdrawal. The elevated glutamate released in the hippocampus during the first cycle of ethanol withdrawal episode was exacerbated in subsequent withdrawal episodes. Acamprosate, a drug used during human alcohol detoxification, is able to completely block the glutamate increase observed during the first as well as the third withdrawal of ethanol. In ethanol-naïve rats, there was no change in the glutamate microdialysate content after an acute ethanol injection. However, when repeated ethanol injections were cued with a vinegar stimulus that had previously been associated with the same ethanol injection, a significant increase in glutamate microdialysate content was assayed. Furthermore, when the cue was omitted, the ethanol injection induced no changes in glutamate microdialysate content in rats that had been previously ethanol conditioned. By comparison, a saline injection had no effect on extracellular glutamate concentration in rats naïve for ethanol as well as in rats daily administered with repeated ethanol injections that were not paired with the cue. It appears probable that these conditioned responses by extracellular glutamate concentrations may participate in the environmental cue-induced conditioned cravings for ethanol that are thought to be related to the high frequency of relapse in detoxified alcoholics.

AbstractIn this work, 31P phosphorus NMR (31P NMR) studies of the brain have been conducted in rats acutely and chronically intoxicated with ethanol. In both groups, changes in levels of high‐energy phosphates were observed: increase of phosphocreatinine (PCr)/β AaTP and PCr/inorganic phosphate (Pi) in acute and long‐term ethanol exposure, and decrease of Piβ ATP after acute ethanol administration. These changes in high‐energy phosphates, indicative of a reduction of adenosine triphosphate (ATP) and PCr consumption (PCr+ ADP + H+ ATP + Cr; ATP ADP + Pi), suggest a reduction of cerebral metabolism both in acute and chronic ethanol exposure. In addition, in the group of rats chronically intoxicated with ethanol, there were variations in phosphodiester peak intensities (decrease of phosphomonoester (PME)/phosphodiester (PDE), increase of PDE/β ATP), suggesting increased breakdown of membrane phospholipids. These changes could provide a metabolic explanation for the development of cerebral atrophy in chronic alcoholism.

Gamma-aminobutyric acid (GABA) and nitric oxide are two key-transmitters in cerebellar nuclei, the major output of cerebellar circuitry. The aims of this study were to investigate the effects of acute intra-cerebellar administration of ethanol (20 mM) on extra-cellular levels of GABA and on the NMDA-induced nitric oxide (NO) production using microdialysis in the rat. We also studied: (i) the effects of a pre-administration of DNQX, a specific antagonist of AMPA receptors, on NO production, (ii) the effects of a pre-administration of 7-NI (7-nitroindazole, an inhibitor of neuronal nitric oxide synthase NOS) and APV (D-2-amino-5-phosphonovaleric acid, a specific blocker of the NMDA type glutamate receptors) on the actions of alcohol/NMDA on glutamate receptors, and (iii) the in vivo interaction between DNQX, ethanol and NMDA receptor activation. We found that ethanol decreased the amount of extra-cellular GABA, and that this effect was counterbalanced by administration of tiagabine 1 mg/kg, a potent inhibitor of GAT-1 GABA transporter, given by the i.p. route. In loco administration of NMDA increased the levels of NO, as previously reported. A pre-administration of DNQX (500 microM) increased significantly the production of NO up to toxic levels, as well as ethanol administration. A pre-administration of 7-NI or APV reduced significantly the amounts of NO when NMDA and alcohol were infused simultaneously. The combination of ethanol with DNQX was associated with a marked enhancement of the concentrations of NO. The activity of GAT-1 in cerebellar nuclei and around this target, including in glial cells expressing GAT-1 activated by ambient GABA, seems to be spared by ethanol. Tiagabine could be considered as a candidate for future investigational treatments of acute ethanol-induced dysfunction of cerebellar nuclei. We found a potentiation of the production of NO when AMPA antagonists are given simultaneously to ethanol. The hypothesis of AMPA neurotoxicity, which has convincing arguments during chronic exposure, is challenged in this model of acute cerebellar nuclear toxicity of alcohol.

The gastrointestinal tract is the natural habitat for a huge community of microorganisms, comprising bacteria, viruses, fungi and yeast. This microbial ecosystem codevelops with the host throughout life and is subject to a complex interplay that depends on multiple factors including host genetics, nutrition, life-style, stress, diseases and antibiotics use. The gut microbiota, that refers to intestinal bacteria, has profound influence on the host immune system, metabolism and nervous system. Indeed, intestinal bacteria supply the host with essential nutrients such as vitamins, metabolize bile acids and undigested compounds, defend against pathogen invasion, participate to the development of the intestinal architecture and the intestinal immune system and play an important role in the maintenance of the gut barrier function. More recently, the gut microbiota has been shown to influence brain functions, such as myelin synthesis, the blood-brain barrier permeability and neuroinflammatory responses but also mood and behavior. The cross-talk between microbes and the host implicates a vast array of signaling pathways that involve many different classes of molecules like metabolites produced by the bacteria from dietary or endogenous sources of carbohydrates and proteins (i.e. short-chain fatty acids (SCFAs), indole), neurotransmitters and inflammatory cytokines. This review will focus on the involvement of the gut microbiota in the pathophysiological aspects of alcohol dependence related to the gut barrier function, liver damage and psychological disturbances. We will also discuss the possibility to create new and realistic humanized animal models of alcohol dependence by the use of fecal transplantation.

In recent microdialysis studies, increased extracellular concentrations of taurine after high ethanol dose administration were identified in various rat brain regions. The mechanisms by which ethanol caused these increases in extracellular taurine concentration remained unclear but could be related to ethanol-induced cell swelling. The aim of the current study was to investigate whether changes in the body osmotic state modulate the effects of ethanol on brain extracellular taurine concentrations. In several groups of rats, brain hypoosmotic or hyperosmotic states were superimposed on acute ethanol (2.0-g/kg) injections, and extracellular taurine concentrations within the nucleus accumbens were assessed by using an intracerebral microdialysis procedure. A hypoosmotic state was obtained by systemic administration of water while hyperosmotic states were induced by intraperitoneal injections of hypertonic saline solutions (1.8% or 3.6% saline). In isoosmotic conditions, ethanol induced an immediate and significant increase in taurine microdialysate content, confirming results of previous studies. However, the effects of ethanol on taurine concentrations were modulated by osmotic manipulations. Hypoosmotic conditions significantly potentiated ethanol-induced taurine release. In contrast, ethanol-induced increases in extracellular taurine levels were attenuated by 1.8% saline injection and totally prevented by 3.6% saline administration. These results strongly argue in favor of a primary role of osmoregulation in ethanol-induced taurine release. Ethanol-induced cell swelling probably activates volume-sensitive channels, and taurine passively diffuses outside the cells along its concentration gradient.

In drug discrimination procedures, the substitution pattern for ethanol of various receptor ligands is dependent upon ethanol training dose, presumably reflecting functionally different concentrations of ethanol in the brain. The discriminative stimulus effects of ethanol are also time-dependent, although very few studies have investigated the time course of ethanol discriminations.The present study investigated the relationship between brain ethanol concentrations (BrEC), as measured by intracranial microdialysis of the nucleus accumbens, and the time course of ethanol discriminative effects.Two groups of rats were trained to discriminate either 1.0 or 2.0 g/kg ethanol from water following a 30-min post-ethanol interval. Following training, the time course of the discriminative stimulus was assessed using a series of abbreviated testing trials at 20-min intervals for 5 h after the administration of various ethanol doses (0, 0.5, 1.0 and 2.0 g/kg). The rats were then fitted with microdialysis probes and the time course of BrECs were determined under conditions similar to the behavioral assessments.BrECs were significantly above zero at 4 min post-gavage and attained peak concentrations of 16 mmol/l, 24 mmol/l and 42 mmol/l at 9 min, 16 min and 95 min after IG administration of 0.5, 1.0 and 2.0 g/kg ethanol, respectively. BrECs were similar in ethanol-naive and ethanol-trained rats, indicating a lack of pharmacokinetic tolerance under these discrimination procedures. The discriminative stimulus effects of ethanol were dose- and time-dependent, with a threshold concentration of approximately 12 mmol/l achieved at 5 min after 1.0 g/kg ethanol gavage in rats trained to discriminate 1.0 g/kg ethanol. Acute tolerance to the discriminative stimulus effects of ethanol was evident from BrECs 2-5 h post-ethanol gavage.Ethanol given intragastrically results in a rapid increase in BrEC, independent of ethanol exposure history. The discriminative stimulus effects of ethanol trained at 30 min post-gavage reflect a specific range of BrEC, and depend on the training dose. These data suggest that qualitatively different stimulus effects of ethanol reflect both different ranges of BrEC, as well as within dose acute tolerance to the discriminative stimulus effects.