RESUMO
AIMS: Chronic myopathy has been described in alcoholics, characterized by atrophy of type II fibres, and vitamin D deficiency. Low serum vitamin D levels are frequent in alcoholics. The possibility exists that serum vitamin D levels are related to muscle changes in a murine experimental model. METHODS: Histological analysis of the right gastrocnemius muscle was performed in four groups of adult Sprague-Dawley rats, sacrificed after 5 weeks of treatment following the Lieber-DeCarli model. We studied the association between muscle histological changes and the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and lipid peroxidation products (malondialdehyde); parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), free testosterone, 1,25 dihydroxyvitamin D3 (vitamin D) and corticosterone; and serum calcium and magnesium. RESULTS: Alcoholic animals showed type IIa and IIb fibre atrophy, especially the low-protein-fed ones, an effect dependent on protein deficiency. A significant relationship was observed between serum vitamin D levels and IIa fibre area (rho = 0.56, P = 0.002), and also, as a trend, between vitamin D and type IIb fibre area (rho = 0.39, p = 0.053); between vitamin D and muscle GPX (rho = 0.40, P = 0.025) and SOD activities (rho = 0.43, P = 0.012). Muscle GPX activity was significantly related with type I fibre area (rho = 0.49, P = 0.01) and muscle SOD, with type IIa fibre area (rho = 0.38, P = 0.045). Serum testosterone was also related with type IIa fibre area (rho = 0.61, P < 0.001). No relation was observed between serum PTH, corticosterone, or IGF-1 and fibre area PTH and antioxidant systems. Multiple regression analysis disclosed that the only parameter independently related with type IIa fibre area was serum vitamin D. CONCLUSION: Low vitamin D levels are related to muscle fibre atrophy, and altered levels of muscle antioxidant enzymes could play a role in alcoholic myopathy.
Assuntos
Depressores do Sistema Nervoso Central/toxicidade , Etanol/toxicidade , Fibras Musculares Esqueléticas/patologia , Doenças Musculares/induzido quimicamente , Doenças Musculares/patologia , Deficiência de Vitamina D/patologia , Animais , Antioxidantes/metabolismo , Atrofia , Cálcio/sangue , Glutationa Peroxidase/metabolismo , Hormônios/sangue , Magnésio/sangue , Masculino , Malondialdeído/metabolismo , Fibras Musculares de Contração Rápida/patologia , Músculo Esquelético/patologia , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Albumina Sérica/metabolismo , Superóxido Dismutase/metabolismo , Vitamina D/metabolismoRESUMO
Diarrhoeic diseases caused by water and food contaminated by enteropathogens continue to be an important cause of morbidity in countries with a low level of development. Some 50,000 cases of diarrhoea in travellers are estimated in the world every day, and this is the main cause of consultation by travellers who return from undeveloped zones. The principal determinant of risk is the place of destination; there are significant differences between different regions with respect to risk and to the aetiology of the diarrhoea. The most frequent cause of diarrhoeas is of bacterial origin, which represents between 60 and 85% of the cases, while parasites represent 10% and some 5% are produced by viruses. Although it normally follows a benign course, complications can arise, with mortality being only exceptionally associated to this disease. Prevention is essentially based on strictly following elemental hygienic measures and avoiding the ingestion of foodstuffs and drinks with a risk of contamination. Prophylaxis with antibiotics is only advisable in journeys of short duration, in which the risk and/or seriousness of diarrhoeas, above all in immunosuppressed patients, are higher than the possible collateral effects. The treatment of diarrhoea in the traveller is based on adequate hydration, and the use of microbians is reserved for moderate and serious situations, with quinolones being the drug of choice. Rifaximine is a new drug approved for the treatment of diarrhoeas in the traveller, above all in areas with enteropathogens that are resistant to quinolones.
Assuntos
Diarreia , Viagem , Diarreia/diagnóstico , Diarreia/epidemiologia , Diarreia/etiologia , Diarreia/terapia , Humanos , Fatores de RiscoRESUMO
Ethanol consumption leads to bone alterations, mainly osteoporosis. Ethanol itself may directly alter bone synthesis, but other factors, such as accompanying protein malnutrition--frequently observed in alcoholics, chronic alcoholic myopathy with muscle atrophy, alcohol induced hypogonadism or hypercortisolism, or liver damage, may all contribute to altered bone metabolism. Some data suggest that zinc may exert beneficial effects on bone growth. Based on these facts, we analyzed the relative and combined effects of ethanol, protein malnutrition and treatment with zinc, 227 mg/l in the form of zinc sulphate, on bone histology, biochemical markers of bone formation (osteocalcin) and resorption (urinary hydroxyproline excretion), and hormones involved in bone homeostasis (insulin growth factor 1 (IGF-1), vitamin D, parathormone (PTH), free testosterone and corticosterone), as well as the association between these parameters and muscle fiber area and liver fibrosis, in eight groups of adult Sprague Dawley rats fed following the Lieber de Carli model during 5 weeks. Ethanol showed an independent effect on TBV (F=14.5, p<0.001), causing it to decrease, whereas a low protein diet caused a reduction in osteoid area (F=8.9, p<0.001). Treatment with zinc increased osteoid area (F=11.2, p<0.001) and serum vitamin D levels (F=3.74, p=0.057). Both ethanol (F=45, p<0.001) and low protein diet (F=46.8, p<0.01) decreased serum osteocalcin levels. Ethanol was the only factor independently related with serum IGF-1 (F=130.24, p<0.001), and also showed a synergistic interaction with protein deficiency (p=0.027). In contrast, no change was observed in hydroxyproline excretion and serum PTH levels. No correlation was found between TBM and muscle atrophy, liver fibrosis, corticosterone, or free testosterone levels, but a significant relationship was observed between type II-b muscle fiber area and osteoid area (rho=0.34, p<0.01). Osteoporosis is, therefore, present in alcohol treated rats. Both alcohol and protein deficiency lead to reduced bone formation. Muscle atrophy is related to osteoid area, suggesting a role for chronic alcoholic myopathy in decreased bone mass. Treatment with zinc increases osteoid area, but has no effect on TBV.
Assuntos
Osso e Ossos/patologia , Depressores do Sistema Nervoso Central/toxicidade , Etanol/toxicidade , Osteoporose/induzido quimicamente , Zinco/farmacologia , Animais , Osso e Ossos/efeitos dos fármacos , Suplementos Nutricionais , Eletrólitos/sangue , Hormônios/sangue , Hidroxiprolina/urina , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Fibras Musculares Esqueléticas/patologia , Doenças Musculares/induzido quimicamente , Doenças Musculares/patologia , Tamanho do Órgão/efeitos dos fármacos , Osteoporose/patologia , Deficiência de Proteína/complicações , Deficiência de Proteína/patologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Albumina Sérica/metabolismo , Coluna Vertebral/patologiaRESUMO
A chronic form of myopathy has been described in alcoholics, characterized by atrophy of type II fibers, due both to reduced protein synthesis and increased protein breakdown. Increased production of reactive oxygen species could probably play a role in increased protein breakdown. In addition, treatment with zinc might be beneficial, since it acts as a cofactor of several enzymes involved in the synthesis of proteins and antioxidants as copper-zinc-superoxidedismutase (SOD) and selenium dependent glutathione peroxidase (GPX). Based on these facts, we analyze the relative and combined effects of ethanol, protein malnutrition and treatment with zinc, 227 mg/l in form of zinc sulphate, on muscle changes in 8 groups of adult Sprague-Dawley rats fed following the Lieber-de Carli model during 5 weeks. We also study the association between muscle histological changes and the activity of GPX, SOD and lipid peroxidation products (MDA), with hormones such as IGF-1, and with trace elements involved in antioxidant systems and/or in lipid peroxidation, such as selenium, copper, zinc, and iron. We found type IIa and IIb fiber atrophy in the alcoholic animals, especially in the low-protein fed ones. This effect was mainly due to protein deficiency. Zinc played no role at all. Muscle iron increased in ethanol, low protein fed rats, either with or without zinc, and was directly related with muscle MDA levels, which in turn were related with muscle atrophy, as was also found for serum IGF-1 levels. Ethanol was the main responsible for all these changes, although protein undernutrition also played an independent role in MDA levels. A positive interaction between ethanol and protein deficiency on serum IGF-1 was also detected. These results suggest that both protein deficiency and ethanol contribute to muscle atrophy observed in alcoholized rats; this atrophy is associated with increased lipid peroxidation and muscle iron overload. Treatment with zinc sulphate confers no benefit.
Assuntos
Depressores do Sistema Nervoso Central/toxicidade , Suplementos Nutricionais , Etanol/toxicidade , Doenças Musculares/induzido quimicamente , Doenças Musculares/prevenção & controle , Zinco/uso terapêutico , Animais , Antioxidantes/metabolismo , Cobre/metabolismo , Glutationa Peroxidase/metabolismo , Hormônios/sangue , Ferro/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Fibras Musculares Esqueléticas/patologia , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Doenças Musculares/patologia , Deficiência de Proteína/metabolismo , Ratos , Ratos Sprague-Dawley , Selênio/metabolismo , Albumina Sérica/metabolismo , Superóxido Dismutase/metabolismo , Zinco/metabolismoRESUMO
Protein undernutrition, alterations of hormones such as IGF-1, testosterone and cortisol, and increased lipid peroxidation-which may be related with deranged metabolism of some elements such as iron (Fe), zinc (Zn), manganese (Mn), selenium (Se) or copper (Cu)-may contribute to muscle damage in non alcoholic cirrhosis. Here, we analyse the effect of protein deficiency on muscle Cu, Fe, Zn, Mn and Se in carbon-tetrachloride (CCl(4)) induced liver cirrhosis. We also study the association between protein undernutrition and these trace elements with the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and lipid peroxidation products, and how all these are related with muscle morphological changes in 40 male adult Sprague-Dawley rats. Liver cirrhosis was induced by intraperitoneal injection of CCl(4) to 10 rats fed a 2% protein diet, and to another 10 fed a 18% protein control diet. Two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. After sacrifice (6 weeks later), we found type IIa fibre atrophy in the cirrhotic animals, especially in the low-protein fed ones and this was due to protein deficiency. Muscle Fe increased in low protein fed cirrhotic rats. No relationship was found between muscle changes and any of the hormones, enzymes and trace elements analysed, or with liver fibrosis. These results suggest that muscle atrophy observed in CCl(4)-induced cirrhosis is related with protein deficiency, but not with cirrhosis itself.
Assuntos
Intoxicação por Tetracloreto de Carbono/patologia , Cirrose Hepática Experimental/patologia , Músculo Esquelético/patologia , Deficiência de Proteína/patologia , Adenosina Trifosfatases/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Corticosterona/sangue , Dieta , Glutationa Peroxidase/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Ratos , Ratos Sprague-Dawley , Selênio/metabolismo , Albumina Sérica/metabolismo , Superóxido Dismutase/metabolismo , Testosterona/sangue , Oligoelementos/metabolismoRESUMO
In liver cirrhosis, liver tissue becomes progressively substituted by fibrosis, ultimately leading to architectural distortion, liver circulatory changes, and liver failure. Some data support the hypothesis that protein undernutrition may play a role in the development and progression of nonalcoholic liver cirrhosis and that this progression is at least partially mediated by changes in glutathione peroxidase (GPX), superoxide dismutase (SOD), and other antioxidative systems, leading to an increase in lipid peroxidation. We analyzed the effects of protein deficiency on liver Cu, Fe, Zn, Mn, and Se in carbon tetrachloride (CCl4)-induced liver cirrhosis, the relation of protein undernutrition and these trace elements with the activity of some hepatic antioxidative enzymatic mechanisms, and the relation of all of them with morphological and biochemical changes in 40 male adult Sprague-Dawley rats divided in four groups. Liver cirrhosis was induced by intraperitoneal injection of CCl4 to 10 rats fed a 2% protein diet and another 10 fed a 18% protein control diet; two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. The study period lasted 6 wk. GPX, SOD, and lipid peroxidation products as well as Zn, Cu, Mn, Se, and Fe were determined in liver samples. We found that liver GPX and Se were reduced in the cirrhotic animals, especially in the low-protein-fed ones, protein deficiency, but not cirrhosis, exerting the main effects. A close correlation was found between liver GPX and serum albumin and weight loss and an inverse one among GPX and hepatocyte ballooning, liver fibrosis, and fat, histomorphometrically determined. These results suggest a pathogenetic role of decreased GPX in the progression of liver disease, which may become enhanced by concomitant protein undernutrition. In addition to iron, the levels of which were increased in the malnourished rats, no differences were found regarding the other trace elements, SOD activity, and lipid peroxidation products.
Assuntos
Antioxidantes/metabolismo , Tetracloreto de Carbono/farmacologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/metabolismo , Fígado/metabolismo , Deficiência de Proteína/metabolismo , Oligoelementos/análise , Animais , Dieta , Glutationa Peroxidase/análise , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Cirrose Hepática Experimental/enzimologia , Cirrose Hepática Experimental/patologia , Masculino , Malondialdeído/análise , Malondialdeído/metabolismo , Camundongos , Deficiência de Proteína/enzimologia , Ratos , Ratos Sprague-Dawley , Selênio/análise , Selênio/metabolismo , Superóxido Dismutase/análise , Superóxido Dismutase/metabolismo , Oligoelementos/metabolismoRESUMO
Chronic alcoholics frequently show associated malnutrition. Both ethanol and malnutrition exert profound changes on zinc and copper metabolism. In this study, we found higher hair zinc and copper values in 43 male alcoholics than in 39 controls. Hair copper was significantly related to the amount of ethanol consumed, whereas hair zinc was higher in consumers of distilled beverages. No relation was observed between hair zinc and copper and nutritional status, kind of diet consumed, style of life, and liver cirrhosis. Consequently, hair zinc and copper levels are related only with alcohol intake.
Assuntos
Alcoolismo/metabolismo , Cobre/análise , Cabelo/química , Zinco/análise , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Alcoolismo/complicações , Peso Corporal , Comportamento Alimentar , Humanos , Masculino , Pessoa de Meia-Idade , Distúrbios Nutricionais/complicações , Distúrbios Nutricionais/metabolismo , Fenômenos Fisiológicos da NutriçãoRESUMO
This study was performed in order to analyse the prevalence, clinical characteristics and mortality of heavy drinkers among hospitalized patients during a 2-year period. Chronic excessive alcohol consumption (daily intake >80 g of ethanol for males and >40 g for females) was found in 278 of 2913 hospital admissions and was strongly associated with the male sex (90.69%). Heavy drinkers were significantly younger than other admissions (15 and 10 years for men and women, respectively), but showed similar mortality rates to other admissions, despite a much earlier age at death (19.5 years for men and 22 years for women). There was a trend towards higher mortality rates among severe alcoholic women than severe alcoholic men and non-alcoholic women. Liver cirrhosis was the entity most frequently observed in the heavy drinkers, and was significantly more prevalent in alcoholic women.