Neuromuscular disorders in chronic alcohol intoxication

The paper reviews the present-day Russian and foreign literature on neuromuscular disorders in chronic alcohol intoxication. The most common manifestations of alcohol disease include alcoholic polyneuropathy (PNP) and alcohol-induced skeletal muscle injury. The clinical polymorphism of alcoholic PNP is discussed. The paper considers a chronic sensory automatic form due to the direct toxic effects of ethanol and its metabolites during long-term alcohol intoxication, as well as acute/subacute sensorimotor neuropathy, the basis for the pathogenesis of which is B group vitamins, predominantly thiamine, deficiency that develops in the presence of drinking bouts concurrent with malnutrition and/or alcohol-related gastrointestinal tract diseases. In addition to nonuse of alcohol and a properly balanced diet, antioxidant therapy with alphalipoic acid and neurotropic B group vitamins is considered to be pathogenetic therapy for neuropathy. The most common and least studied clinicalform of alcohol-induced musculoskeletal injury is chronic alcoholic myopathy (AM), the diagnostic standard for which is morphometricand immunohistochemical examination of a muscle biopsy specimen. The morphological base for this form of myopathy is predominantly type 2 muscle fiber atrophy caused by impaired protein synthesis and a decreased regenerative potential of muscle fiber. The efficacy of antioxidants and leucine-containing amino acid mixtures in the treatment of chronic AM is discussed

Вопросы диагностики и патогенеза хронической алкогольной миопатии

Peripheral neuromuscular apparatus lesion is a common complication of chronic alcohol intoxication. Alcohol-induced skeletal muscle diseaseis least studied now. A comprehensive clinical, neurophysiological, and morphological examination was made in 42 patients with chronic alcoholintoxication during this study. All the patients underwent skeletal muscle biopsy followed by muscle fiber morphometry. There was both selective type 2 muscle fiber atrophy and diffuse types 1 and 2 muscle fiber atrophic changes. The clinical manifestations of skeletal muscle disease corresponded to the degree of an atrophic process. There was impairment in the main components of protein synthesis at both intracellular and systemic regulation levels.Поражение периферического нервно-мышечного аппарата – частое осложнение хронической алкогольной интоксикации. Наименее изучено в настоящее время поражение скелетных мышц алкогольного генеза. В ходе настоящего исследования проведено комплексное клиническое, нейрофизиологическое, морфологическое обследование 42 пациентов с хронической алкогольной интоксикацией. Всем пациентам проводилась биопсия скелетной мышцы с последующей морфометрией мышечных волокон. Отмечались как селективная атрофия мышечных волокон 2-го типа, так и диффузные атрофические изменения мышечных волокон 1-го и 2-го типов. Клинические проявления поражения скелетных мышц соответствовали выраженности атрофического процесса. Выявлено нарушение основных звеньев синтеза белка как на внутриклеточном, так и на системном уровне регуляции

LIN-44/Wnt Directs Dendrite Outgrowth through LIN-17/Frizzled in C. elegans Neurons

Nervous system function requires proper development of two functional and morphological domains of neurons, axons and dendrites. Although both these domains are equally important for signal transmission, our understanding of dendrite development remains relatively poor. Here, we show that in C. elegans the Wnt ligand, LIN-44, and its Frizzled receptor, LIN-17, regulate dendrite development of the PQR oxygen sensory neuron. In lin-44 and lin-17 mutants, PQR dendrites fail to form, display stunted growth, or are misrouted. Manipulation of temporal and spatial expression of LIN-44, combined with cell-ablation experiments, indicates that this molecule is patterned during embryogenesis and acts as an attractive cue to define the site from which the dendrite emerges. Genetic interaction between lin-44 and lin-17 suggests that the LIN-44 signal is transmitted through the LIN-17 receptor, which acts cell autonomously in PQR. Furthermore, we provide evidence that LIN-17 interacts with another Wnt molecule, EGL-20, and functions in parallel to MIG-1/Frizzled in this process. Taken together, our results reveal a crucial role for Wnt and Frizzled molecules in regulating dendrite development in vivo

Neurological complications of alcoholic disease and ways of their correction

The problem of alcohol abuse and its social and medical consequences has remained relevant for many years. Damage to the nervous system is one of the most common manifestations of alcoholic disease. The effect of ethanol and its metabolites results in damage to all parts of the nervous system and skeletal muscles. The paper provides a brief overview of Russian and foreign literature on the neurological manifestations of chronic alcohol intoxication. It considers modern ideas about the pathogenesis of alcoholic neuropathy (APN). It also discusses differences in the clinical presentation, course, and developmental mechanisms of the main (chronic toxic and acute/subacute) forms of APN associated with thiamine deficiency. The paper notes difficulties in diagnosing peripheral nerve damage, especially in the early stages of the disease and describes modern methods for objectifying damage to thin nerve fibers in chronic APN. It presents approaches to treating alcohol-induced damage to the peripheral nervous system, by taking into account the leading mechanisms of pathogenesis. Special attention is paid to B-complex vitamins and alpha-lipoic acid preparations frequently used in this disease, to the mechanisms of their therapeutic action, and to the evaluation of their efficacy in APN

Nervous system injury in alcoholic disease

The paper considers various variants of nervous system injury in alcoholic disease. It discusses the epidemiology, pathogenesis, diagnosis, and clinical manifestations of central and peripheral nervous system lesions in the presence of acute and chronic alcohol intoxication. Attention is paid to the issues of etiotropic, pathogenetic, and symptomatic treatment for neurological manifestations of alcoholic disease and to the role of neurotropic B vitamins in the treatment of alcohol-induced deficiency and non-deficiency states

Trimetazidine MR effects on heart remodeling in stable coronary heart disease patients

Aim. To study trimetazidine MR effects on left ventricular (LV) remodeling in stable coronary heart disease (CHD) patients with completely controlled effort angina and arterial hypertension (AH), who received combined treatment. Material and methods. In total, 114 individuals were examined: Group I – 65 healthy volunteers (mean age 31,38 years); Group II - 49 untreated CHD and AH patients (mean age 62,32 years). All participants underwent transthoracic echocardiography, with calculation of systolic and diastolic spherical index, remodeling index (RI), systolic and diastolic myocardial stress (MSs, MSd), LV myocardial mass index, LV relative wall thickness (RWT). Results. After three months of combined, four-component treatment, clinical stabilization was not associated with significant changes in LV remodeling, only MSs reduced significantly after adding Preductal MV to the treatment. In stable good clinical status, no obvious clinical dynamics, and unchanged ejection fraction, structural and functional cardiac parameters improved substantially, with reduction (р<0,00001) in MSs (145,68±11,35 and 124,51±7,89); MSd (160,72±16,78 and 156,24±12,11), end-diastolic pressure (14,81±3,16 and 11,9±1,91 mm Hg), end-diastolic LV wall strain (1967,33±337,27 and 1519,99±224,74 dyne/cm2), as well as with increase in RI (93,72±8,48 and 100,87±9,74). LV diastolic function parameters improved, NYHA functional class reduced. Conclusion. Trimetazidine MR beneficial effects on myocardial elasticity, contractility, and remodeling were demonstrated. The medication can be used as an anti-remodeling agent in combined CHD treatment

Change in the content of titin and nebulin and their phosphorylation level in the quadriceps femoris muscle in chronic alcoholic myopathy

Objective: to assess the structural and functional state of skeletal muscles in the hip, as well as changes in the content of the sarcomere cytoskeleton proteins titin and nebulin and their phosphorylation level in patients with chronic alcohol intoxication.Patients and methods. Thirteen patients (4 men and 9 women; mean age, 38.9±9.9 years) with chronic alcohol intoxication were examined. The average duration of regular consumption of alcoholic beverages was 7.6±3.7 years. The mean amount of alcohol consumed per week was 48.2±13.1 units. A control group included 10 healthy volunteers matched for age and sex. A neurological examination was performed according to the generally accepted scheme. Laboratory tests involved blood biochemical analysis estimating the levels of liver enzymes, creatine phosphokinase (CPK), and insulin-like growth factor-1 (IGF-1). All the patients underwent hip magnetic resonance imaging (MRI), followed by assessment of the degree of muscle tissue damage and by determination of the volume of anterior and posterior thigh muscles. The content of titin and nebulin and their phosphorylation level were determined in the muscle tissue samples obtained by an open biopsy from the lateral head of the quadriceps femoris muscle.Results and discussion. Four (30.8%) patients were found to have proximal leg muscle weakness; the degree of paresis was the same in the anterior and posterior thigh muscles. There was a significant increase in the plasma level of liver enzymes; the CPK level remained within the reference values; there was a tendency towards lower IGF-1 levels. Analysis of MRI data showed that 7 (53.8%) patients had fatty degeneration in the thigh muscles. Quantitative evaluation ascertained a significant symmetrical decrease in the volume of anterior thigh muscles and a tendency towards a symmetrical reduction in that in the posterior thigh muscle compared to the control. Analysis of the content of titin and nebulin in the lateral head of the quadriceps femoris muscle revealed a significant decrease in the percentage of nebulin (81.1%; p < 0.01) and intact titin-1 (T1) isoforms (83.6%; p < 0.01). The percentage of proteolytic titin-2 (T2) fragments in the muscle of patients did not differ significantly from that in the control group. Estimating the phosphorylation level of the structural muscle proteins showed no significant differences when compared to the control.Conclusion. Anterior and posterior thigh muscle weakness should be considered as the main clinical manifestation of chronic alcoholic myopathy (CAM) in the absence of biochemical and neurophysiological markers of the disease. Lower extremity muscle MRI that can reveal a lower muscle volume concurrent with fatty degeneration is a non-invasive informative diagnostic technique for CAM. The pathogenesis of skeletal muscle atrophy in chronic alcohol intoxication involves the sarcomere structural proteins titin and nebulin, which regulate the interaction of the major contractile proteins actin and myosin, and whole muscle contraction