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Chronic alcohol abuse is a ubiquitous health and societal problem, with a growing prevalence in the older population. Alcoholism is a source of substantial deterioration in brain tissue and has been consistently observed in vivo and postmortem in white matter. To quantify the potential compounded effect of age and alcoholism, we used conventional structural MRI and diffusion tensor imaging (DTI) to examine the macrostructural and microstructural integrity of the corpus callosum, one of the most prominent white matter structures of the brain, in 131 adults, age 27-75 years. Compared with the 74 controls, the 40 alcoholic men and 17 alcoholic women, who were abstinent from alcohol for an average of 3 months, showed similar patterns and extents of callosal shrinkage, which was greatest in the genu and body and less prominent in the splenium. Microstructural integrity was measured with DTI as fractional anisotropy, an index of intravoxel orientational coherence of white matter fibers, and bulk mean diffusivity, an index of the amount of intravoxel water motility. The macrostructural shrinkage was accompanied by abnormalities in anisotropy and diffusivity of the microstructural environment of these callosal regions, indicative of disruption of structural constituents of local brain white matter. Correlational analyses revealed an age-alcohol interaction, where older alcoholics had smaller genu and splenium and higher diffusivity in these regions than younger alcoholics. Significant correlations between regional MRI and DTI measures and performance on working memory, visuospatial ability, and gait and balance provided evidence for the functional ramifications of the callosal abnormalities in the alcoholics. Thus, despite abstinence from alcohol, the interaction of age and recent alcoholism history exerted a compounded untoward effect on callosal macrostructure and microstructure.

Young and aged rats were treated chronically with ethanol or scopolamine. Muscarinic receptors were measured in cerebral cortex, hippocampus and striatum. Following scopolamine treatment muscarinic receptor density in cerebral cortex, hippocampus and striatum of young rats increased by 34, 57 and 27%, respectively; in brains of aged rats the increase was 41% in cerebral cortex, 43% in hippocampus and nil in striatum. Affinity of muscarinic receptors was not changed by scopolamine treatment. Following chronic ethanol administration there was a 48% increase in cortical muscarinic receptor density in young, but not aged rats. The density of muscarinic receptors in hippocampus and striatum of both young and aged rats was not affected by ethanol treatment. Affinity of receptors in hippocampus of aged, ethanol-treated rats was increased compared to age-matched controls. Adaptative responses of the muscarinic receptor/transducer system to neurotransmitter availability are present in both young and aged rats, both the ethanol-induced response is present only in young animals. This suggests differences in the mechanism of action of ethanol and receptor agonists and antagonists in modulating receptor plasticity.

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.

Task-related EEG changes were studied during the performance of a mental arithmetic task, as influenced by low alcohol dosages with the presumption that even "social" drinking may have detrimental effect.A mental arithmetic task was used in which addition and working memory effort was required. EEG spectra with an emphasis on the theta band, error rate and reaction time were analyzed in 5 (control, task, placebo-task, low-dose task [0.2 g/kg alcohol], high-dose task [0.4 g/kg alcohol]) conditions. Blood alcohol concentrations were measured.Reaction time was shortest in the placebo condition. No significant alcohol effect was seen for error rate. Task-related significant theta power increase was observed especially in the frontal area and in the left hemisphere which was reversed, although not in a significant way, by alcohol.No detrimental alcohol effect was seen on behavioral indices of task performance. However, the ethanol-induced moderate reduction of the task-related frontally dominant theta increase, probably corresponding to working memory demand, is a modest but clear electrophysiological sign of alcohol effect in this low-dose range.

The purpose of the current study was to ascertain whether ethyl nitrite could be detected in vitro from the reaction of ethanol with peroxynitrite, as well as after administration of ethanol to mice. Ethyl nitrite analyte was determined by using gas chromatography--mass spectrometry with headspace analysis with the use of a solid-phase microextraction device. Peroxynitrite was allowed to react with ethanol under a variety of conditions in vitro. Ethyl nitrite was generated when peroxynitrite was allowed to react with ethanol. Male, inbred short-sleep mice were injected intraperitoneally with either ethanol [5.2 g/kg; 15.0% (weight/volume) ethanol in saline] or a 50:50 mixture of deuterium-labeled ethanol (D5-ethanol) and ethanol. Blood samples, as well as whole brain and liver sections, were obtained from mice 30 min later for determination of ethanol, D5-ethanol, ethyl nitrite, and deuterium-labeled ethyl nitrite (D5-ethyl nitrite). Time courses for the appearance of ethyl nitrite in blood samples, as well as in whole brain and liver sections, obtained from mice were carried out. After ethanol administration, ethyl nitrite was detected and quantitated in mouse blood, brain, and liver. A small fraction of ethyl nitrite was present. When a 50:50 mixture of ethanol and D5-ethanol was given to animals, both ethyl nitrite and D5-ethyl nitrite were found in blood and brain in approximately the same ratio as that of ethanol and D5-ethanol. The level of D5-ethyl nitrite in liver was more than twice that of ethyl nitrite, indicating a possible isotope effect in the metabolism of ethyl nitrite. Ethyl nitrite is a new metabolite of ethanol in vivo. The mechanism of ethyl nitrite formation is most likely the reaction of ethanol with peroxynitrite generated in vivo from nitric oxide.

IT is not known whether alcoholism is an inherited disease, although some aspects of this complex disorder have been shown to be genetically determined. One might expect that genetic factors could influence either the tendency of an individual to drink excessively or the sensitivity of individuals to the effects of a given alcohol intake, or both. Most genetic work has dealt with drinking behaviour. For example, it is well known that inbred strains of mice differ in voluntary alcohol intake1. In man, twin studies have shown higher concordance in monozygotic than dizygotic pairs with respect to patterns of drinking2,3. Alcoholism is frequent among offspring of alcoholics, even when raised away from their biological parents4,5. Genetic differences in sensitivity to acute effects of alcohol have been shown in mice6 and in human populations (Caucasoid compared with Mongoloid)7. I report here that genes influence the severity of alcohol withdrawal effects in mice. This may mean that vulnerability to physical dependence can be inherited.

Chronic exposure to ethanol can cause deficits in learning and memory. It has been suggested that withdrawal is potentially more damaging than the ethanol exposure per se. Therefore, we explored the effect of repeated episodic exposure to ethanol on key regulators of cortical activity, the neurotrophins. Rats were exposed to ethanol via a liquid diet for 3 days per week for 6-24 weeks. Control rats were pair-fed an isocaloric liquid diet or ad libitum fed chow and water. The concentrations of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were determined using enzyme-linked immunosorbant assays (ELISAs). Five telencephalic structures were examined: parietal cortex, entorhinal cortex, hippocampus, the basal nucleus, and the septal nuclei. All five areas expressed each of the three neurotrophins; BDNF was most abundant and NGF the least. The parietal cortex was susceptible to ethanol exposure, NGF and BDNF content increased, and NT-3 content fell, whereas no changes were detectable in the entorhinal cortex. In the hippocampus, the amount all three neurotrophins increased following episodic ethanol exposure. Neurotrophin content in the two segments of the basal forebrain was affected; NGF and NT-3 content in the basal forebrain was reduced and NGF and BDNF content in the septal nuclei was increased by ethanol exposure. In many cases where ethanol had an effect, the change was transient so that by 24 weeks of episodic exposure, no significant changes were evident. Thus, the effects of ethanol are site- and time-dependent. This pattern differs from changes caused by chronic ethanol exposure, hence, neurotrophins must be vulnerable to the effects of withdrawal. Furthermore, the ethanol-induced changes do not appear to fit a model consistent with retrograde regulation, rather they suggest that neurotrophins act through autocrine/paracrine systems.

Previously, it has been suggested that acute ethanol (alcohol) administration can result in concentration-dependent vasoconstriction and decreased cerebral blood flow. Here, we present in vivo results using rapid (240 nm/min) optical backscatter measurements, with an intact cranial preparation in the rat, indicating that acute infusion of ethanol directly into the rat brain rapidly produces dose-dependent vasoconstriction of the cerebral microcirculation associated with a pronounced reduction in tissue blood content, pronounced rises in deoxyhemoglobin, significantly increased levels of reduced cytochrome oxidase and microvascular damage as the dose increases. Furthermore, we present in vivo experiments demonstrating the capability of magnesium ions (Mg(2+)) to attenuate and prevent these deleterious responses. Optical backscatter spectra (500-800 nm) were obtained by directing a single sending and receiving fiber to a portion of the left parietal cranium (in anesthetized rats), shaved to a translucent appearance to facilitate optical penetration. In the absence of added Mg(2+), infusion of a 10% solution of ethanol at 0.34 ml/min ( approximately 26.8 mg/min) produced prompt vasoconstriction as evidenced by a greater than 90% loss of oxyhemoglobin from the field-of-view and increases in levels of reduced cytochrome oxidase to between 50% and >90%. These effects were partially, to nearly completely, attenuated by the addition of MgCl(2) to the infusate containing added ethanol. Of special interest was the observation that attenuation of the vasoconstrictive effect of ethanol by Mg(2+) persisted despite a subsequent ethanol challenge without added Mg(2+). The results obtained demonstrate that, depending on dose, ethanol can produce prompt and severe vasoconstriction of the intact cerebral microcirculation and that infusion of moderate doses of Mg(2+) can largely attenuate and prevent this response. We conclude that appreciable, graded changes in cerebral cytochrome oxidase aa(3), blood volume and the state of hemoglobin occur at minimal tissue levels of ethanol which can be modulated by Mg(2+).