RESUMO
AIMS AND BACKGROUND: Alpha Klotho is a transmembrane protein that serves as co-receptor for FGF23. Ectodomain of membrane bound α Klotho may be shed by membrane bound proteases (activated, among other factors, by tumor necrosis factor (TNF)-α) generating the soluble form of the protein (sKl) that functions as a hormone by itself. It modulates calcium influx into cells, blunts IGF-1/Insulin signaling, promotes synthesis of antioxidants, generally slows down tumor progression, delays cell senescence, is neuroprotective and promotes oligodendrocyte maturation and myelin synthesis, and muscle rejuvenation. It may be involved in inflammation and exerts antifibrogenic effects. Some of these pathways may become altered in alcoholism or liver cirrhosis, but data are scattered and scarce and an update is required. METHOD: Literature survey. RESULTS AND CONCLUSIONS: Alcohol consumption in non-alcoholics is inversely related to sKl, but alcoholic cirrhotics showed higher-than-normal sKl values in association with liver function derangement. In hepatoma cells, the intensity of Klotho staining was related to faster tumor progression and a shortened life span. Among severe alcoholic cirrhotics sKl is directly related to serum TNF-α levels, and, inversely, to brain atrophy. Given the antioxidant, anti-inflammatory, and antifibrogenic effects of Klotho, perhaps the increase in cirrhosis (and in other inflammatory conditions, such as sepsis or cancer) reflects an attempt to regulate increased inflammation, but clinical and experimental research is urgently needed in this field.
Assuntos
Alcoolismo/fisiopatologia , Glucuronidase/fisiologia , Cirrose Hepática/fisiopatologia , Fator de Crescimento de Fibroblastos 23 , Humanos , Proteínas KlothoRESUMO
INTRODUCTION: Transforming growth factor beta-1 (TGF-ß1) is a pleiotropic cytokine. Its relationship with atherosclerosis is debatable, protective or deleterious effects have been described. Alcoholics are at increased vascular risk. Although TGF-ß1 is increased in alcoholics, its role on vascular risk factors has not been analyzed. This is the objective of this study. PATIENTS AND METHODS: 79 heavy alcoholics and 34 controls were included. Calcium deposition in the aortic arch was assessed in the plain thorax X-ray film. Ankle-brachial index was recorded in 48 patients. All the patients underwent complete laboratory evaluation, including serum levels of TGF-ß1, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, and interferon-γ (IFN-γ).We analyzed the relationships between TGF-ß1 and vascular risk factors by both univariate (parametric or non parametric tests), or multivariate analysis to discern on which variables TGF-ß1 levels depend. RESULTS: Serum TGF-ß1 levels were higher among patients (t = 2.73; P = 0.008), but no differences exist among cirrhotics (17246 ± 11,021 pg/mL) and non-cirrhotics (21,340 ± 12,442 pg/mL). TGF-ß1 showed significant correlations with total cholesterol (r = 0.28; P = 0.017) and HDL- cholesterol (r = 0.25; P = 0.042), and inverse correlations with body mass index (BMI; ρ = -0.37; P = 0.004), IL-4 (ρ = -0.31; P = 0.009), INF-γ (ρ = -0.28; P = 0.001), and IL-6 (ρ = -0.38; P = 0.001). By multivariate analysis, only BMI, IL-6 and HDL-cholesterol showed independent relationships with TGF-ß1. No relationships were observed with ankle-brachial index or calcium in the aortic arch, hypertension, diabetes, left ventricular hypertrophy or atrial fibrillation. CONCLUSION: TGF-ß1 levels are increased in alcoholics, but are unrelated to vessel wall calcification or arterial stiffness.
Assuntos
Alcoólicos , Alcoolismo/sangue , Fator de Crescimento Transformador beta1/sangue , Calcificação Vascular/sangue , Rigidez Vascular/fisiologia , Idoso , Alcoolismo/diagnóstico , Alcoolismo/epidemiologia , Aorta Torácica/metabolismo , Aorta Torácica/patologia , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Calcificação Vascular/diagnóstico , Calcificação Vascular/epidemiologiaRESUMO
AIM: Very few studies have compared the epidemiological characteristics of patients with familial colorectal cancer Type X (FCCTX) with those of sporadic colorectal cancer (S-CRC). The aim of this study was to compare clinicopathological characteristics and survival between FCCTX and S-CRC in patients from a historically isolated geographical region. METHOD: A retrospective study was carried out of patients with S-CRC and FCCTX treated in the Canary Islands. Family and personal history of colorectal cancer (CRC) were recorded, together with genetic (microsatellite instability), immunohistochemical and clinical variables. RESULTS: Forty-eight (10.6%) of 451 patients were classified as FCCTX and the remaining 403 (89.4%) as S-CRC. Age at the diagnosis of tumour was significantly lower in FCCTX than in S-CRC (64.06 ± 12.65 years vs 69.13 ± 10.80 years; P = 0.01; Z = -2.48). Patients with FCCTX had a larger number of synchronous tumours (P = 0.09). Recurrence was significantly higher in FCCTX than in S-CRC (18.7% vs 8.6%; P = 0.01). Survival correlated significantly with the number of first-degree and second-degree relatives with CRC (P = 0.04; OR: 1.368, 95% CI: 1.01-1.84, and P = 0.04; OR: 1.363, 95% CI: 1.08-1.65) and with the total number of cases of CRC in the immediate family (P < 0.01; OR: 1.377, 95% CI: 1.17-1.61). Recurrence-free time was significantly lower in patients with FCCTX (log-rank = 0.01). CONCLUSION: Significant differences were found in several demographic and clinicopathological variables between patients with FCCTX and patients with S-CRC. These included increased tumour presentation under the age of 50 years and a higher recurrence rate in patients with FCCTX, suggesting an increased risk of CRC in this group.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais/epidemiologia , Fatores Etários , Idoso , Neoplasias Colorretais/patologia , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Primárias Múltiplas/patologia , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologiaAssuntos
Tumor Carcinoide/secundário , Nervo Femoral/patologia , Neoplasias do Íleo/patologia , Neoplasias do Sistema Nervoso Periférico/secundário , Idoso , Tumor Carcinoide/diagnóstico por imagem , Feminino , Nervo Femoral/diagnóstico por imagem , Humanos , Neoplasias do Sistema Nervoso Periférico/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
In 117 patients affected by chronic alcoholic liver disease, we have histomorphometrically determined hepatocyte and nuclear areas, total amount of fat and total amount of fibrosis, comparing them with the following clinical and biochemical parameters: ascites, encephalopathy, jaundice, spiders, collateral circulation, splenomegaly, prothrombin activity, serum albumin, gammaglobulin, bilirubin, ASAT, ALAT, GGT, leukocyte and platelet count, and daily consumption of ethanol. Both hepatocyte and nuclear areas closely correlated with most of the parameters indicative of hepatic function derangement, whereas fat amount correlated with them inversely, but positively with the daily consumption of ethanol. The degree of fibrosis was greater in patients with a worse hepatic function, and there was a direct relationship between the degree of fibrosis and hepatocyte and nuclear areas, and an inverse one between the degree of fibrosis and the total amount of fat.
Assuntos
Fígado Gorduroso Alcoólico/patologia , Hepatopatias Alcoólicas/patologia , Fígado/patologia , Adulto , Núcleo Celular/patologia , Doença Crônica , Fígado Gorduroso Alcoólico/fisiopatologia , Feminino , Fibrose , Humanos , Hepatopatias Alcoólicas/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
Serum neopterin levels have been determined by RIA in 105 patients affected by chronic alcoholic liver disease, 68 of them cirrhotics, and in 12 controls. Serum Neopterin was significantly higher in patients than in controls, correlated with Pughs' score and Child's classification, and also with serum laminin and type III collagen N-terminal propeptide, and with histomorphometrically determined liver fibrosis. Serum neopterin levels were higher in patients who died than in survivors, serum neopterin levels over 19.15 nmol/l being associated with higher mortality rates.
Assuntos
Biopterinas/análogos & derivados , Cirrose Hepática Alcoólica/diagnóstico , Adulto , Biópsia , Biopterinas/sangue , Causas de Morte , Feminino , Hepatite B/diagnóstico , Hepatite B/mortalidade , Hepatite B/patologia , Hepatite C/diagnóstico , Hepatite C/mortalidade , Hepatite C/patologia , Humanos , Fígado/patologia , Cirrose Hepática Alcoólica/mortalidade , Cirrose Hepática Alcoólica/patologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Neopterina , Radioimunoensaio , Taxa de SobrevidaRESUMO
Chronic alcoholic liver disease is associated with several immunological alterations: depressed T-cell function, low serum gamma-interferon, and high serum tumour necrosis factor (TNF-alpha) and interleukin levels. Therefore, macrophage activity seems to be enhanced. Some cytokines, such as TNF-alpha, exert adverse effects on chronic alcoholic liver disease, so that protracted activation of macrophages with continuous TNF-alpha production may aggravate alcoholic hepatitis. Based on these facts we have sequentially determined serum levels of TNF-alpha, 1 beta interleukin (IL-1 beta), gamma-interferon and neopterin--a macrophage product--at admission, and at the end of the first, third and sixth weeks after admission, of 43 patients affected by alcoholic hepatitis, and of 20 age-matched sanitary workers as controls. Our patients showed higher levels of neopterin and lower levels of IL-1 beta and gamma-interferon than the controls; TNF-alpha levels in our patients were almost significantly higher than in controls. TNF-alpha levels at admission were higher in the patients who died (P = 0.025). TNF-alpha and neopterin levels showed no trend to normalization in patients who died, with higher levels of neopterin at first and third weeks and higher TNF-alpha and gamma-interferon levels at first week. Using logistic regression analysis, serum TNF-alpha levels at admission showed significant (P = 0.045), independent effects on mortality, as well as serum neopterin (P = 0.0026) at the first week. Thus, enhanced macrophage activity, measured by serum levels of TNF-alpha and neopterin seems to be related to a worse prognosis in alcoholic hepatitis.
Assuntos
Citocinas/sangue , Hepatite Alcoólica/imunologia , Idoso , Biopterinas/análogos & derivados , Biopterinas/sangue , Feminino , Humanos , Interferon gama/sangue , Interleucina-1/sangue , Ativação Linfocitária/imunologia , Ativação de Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Neopterina , Fator de Necrose Tumoral alfa/metabolismoRESUMO
To establish their ability to predict malnutrition, irregular feeding, alcoholic intake, derangement of social and familial links and organic complications (liver cirrhosis) were assessed in 181 hospitalized male alcoholic. BMI was under 18.5 kg/m(2) in 8.9%, between 18.5-20 kg/m(2) in 8.9%, 20-25 kg/m(2) in 42%, 25-30 kg/m(2) in 32.2% and over 30 kg/m(2) in 8.2% of patients. Malnutrition was related to the intensity of ethanol intake, development of social or familial problems, irregularity of feeding habits and cirrhosis with ascites. Irregularity of feeding habits was also related to heavy drinking and to social or familial derangement. By logistic regression analysis, the only variables which independently predict malnutrition were irregular feeding habits and liver cirrhosis with ascites. In a second step, irregular feeding was dependent on social or familial troubles and daily intake of ethanol. So, malnutrition related to alcoholism seems multifactorial in its pathogenesis.
Assuntos
Alcoolismo/complicações , Ascite/etiologia , Comportamento Alimentar , Cirrose Hepática Alcoólica/etiologia , Avaliação Nutricional , Distúrbios Nutricionais/etiologia , Adulto , Idoso , Alcoolismo/psicologia , Relações Familiares , Comportamento Alimentar/psicologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores SocioeconômicosRESUMO
OBJECTIVE: To discern if factors such as organic pathology, sex, duration and/or intensity of drug addiction, alcohol abuse, hepatitis B infection, anorexia with poor food and drink consumption, or disturbance of social and familial networks, are related to an impaired nutritional status in hospitalized drug addicts. DESIGN: Cross-sectional prospective study. SETTING: Detoxication unit and internal medicine unit of a university hospital. PATIENTS: 140 drug addicts without acute organic pathology and 18 with acute organic pathology related to drug addiction. The immunological study was compared with a control group composed of 50 healthy and well-nourished individuals (26 women and 24 men), age-matched with our patients. RESULTS: Drug addicts without organic pathology were under-nourished: 92.4% weighed under the mean weight for the population and 55.7% had had a weight loss above 5%. The distribution of mid-upper arm circumference (MUAC), triceps skinfold (TSF) measurement and mid-arm muscle area (MAMA) compared with the percentiles for the population showed a shift towards lower values. We found a high percentage of patients with a high lymphocyte count (55%). Despite the high lymphocyte count, delayed hypersensitivity was depressed in our patients. Of our patients, 66.4% exhibited anorexia at admission. The mean calorific intake was 978 +/- 89 kcal/day in females and 1265 +/- 64 kcal/day in males. However, in most cases, malnutrition (usually marasmus-like malnutrition) was not very severe; only 30% of the drug addicts weighed less than 80% of the mean weight for the population, or admitted to a weight loss above 10%, and by subjective nutritional assessment, only 18% were deeply malnourished. Otherwise, the nutritional status was very poor in drug addicts with acute organic pathology. We also found a worse nutritional status in our patients related to female sex, intensity of drug addiction, anorexia with poor food and drink consumption, and disturbance of the social and familial networks. CONCLUSIONS: Many drug addicts suffer from calorie and protein malnutrition. This mainutrition is related to female sex, intensity of drug addiction, anorexia and poor food and drink consumption, and disturbance of the social and familial links. Acute organic pathology leads to a significant worsening of the nutritional status of drug addicts.
Assuntos
Alcoolismo/fisiopatologia , Avaliação Nutricional , Desnutrição Proteico-Calórica/fisiopatologia , Abuso de Substâncias por Via Intravenosa/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Adulto , Alcoolismo/psicologia , Alcoolismo/reabilitação , Anorexia/fisiopatologia , Anorexia/psicologia , Anorexia/reabilitação , Cocaína , Ingestão de Energia/fisiologia , Metabolismo Energético/fisiologia , Feminino , Soropositividade para HIV/fisiopatologia , Soropositividade para HIV/psicologia , Soropositividade para HIV/reabilitação , Hepatite B/fisiopatologia , Hepatite B/psicologia , Hepatite B/reabilitação , Dependência de Heroína/fisiopatologia , Dependência de Heroína/psicologia , Dependência de Heroína/reabilitação , Humanos , Contagem de Linfócitos , Masculino , Infecções Oportunistas/fisiopatologia , Infecções Oportunistas/psicologia , Infecções Oportunistas/reabilitação , Estudos Prospectivos , Desnutrição Proteico-Calórica/psicologia , Desnutrição Proteico-Calórica/reabilitação , Abuso de Substâncias por Via Intravenosa/psicologia , Abuso de Substâncias por Via Intravenosa/reabilitação , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Redução de Peso/fisiologiaRESUMO
OBJECTIVE: To assess the nutritional status of drug addicts without acute organic pathology, in order to determine the prevalence of malnutrition and to discern if early HIV infection is associated with a poor nutritional status in this group of patients. DESIGN: Prospective study. SETTING: Detoxication unit of a university hospital. PATIENTS: 140 drug addicts without acute organic pathology. 31 patients were HIV+. No one fulfilled the definition of AIDS. RESULTS: We found that drug addicts were undernourished: 92.4% weighed under the mean populational weight and 55.7% had a weight loss above 5%. The distribution of mid upper arm circumference (MUAC), triceps skinfold (TSF) and mid arm muscle area (MAMA) was lower than a reference normal population. Food intakes were poor; 66.4% of our patients complained of anorexia on admission. The mean caloric intake was 978 +/- 89 kcal/day in females and 1265 +/- 64 kcal/day in males. The mean protein intakes were 39.3 +/- 3.3 g/day in females (0.76 +/- 0.07 g/kg/day) and 49.7 +/- 2.7 g/day in males (0.77 +/- 0.04 g/kg/day). When we compared nutritional parameters between HIV+ and HIV- patients we found no differences. CONCLUSIONS: Nutritional impairment in drugs abusers with early stages of HIV infection should be attributed to drug abuse rather than to HIV infection.
RESUMO
The aim of the present study is to analyse the relative and combined effects of ethanol and protein deficiency on serum testosterone and LH, and on gonadal histology, in ethanol fed rats. The study was performed in 32 animals divided into four groups, fed with the Lieber & DeCarli control, 36% ethanol, 2% protein, and 36% ethanol 2% protein containing diets, respectively. Two months later, rats were anaesthetized with pentobarbital and sacrificed, and the right testes and epididymus were carefully removed. Both ethanol and protein deficiency independently lead to a decrease in serum testosterone levels, and to testicular atrophy, lowest testosterone levels and highest degrees of atrophy being observed in the rats receiving the 36% ethanol, 2% protein containing diet. Both serum testosterone and testicular size and weight significantly correlated with final weight and serum albumin. Hypospermia, atrophy of the seminiferous tubules, and reduced epididymal diameter were also observed in this last group of animals. Thus, protein deficiency may contribute to hypogonadism of alcoholics.
Assuntos
Etanol/farmacologia , Deficiência de Proteína/patologia , Deficiência de Proteína/fisiopatologia , Testículo/patologia , Testículo/fisiopatologia , Animais , Atrofia , Epididimo/patologia , Etanol/administração & dosagem , Hormônio Luteinizante/sangue , Masculino , Tamanho do Órgão , Ratos , Ratos Wistar , Albumina Sérica/metabolismo , Contagem de Espermatozoides , Testosterona/sangueRESUMO
The present study has been performed in order to establish the relative and combined roles of ethanol and malnutrition on liver Fe, Zn, Cu, and Mn alterations in alcoholic male adult Wistar rats, and also the relationships between these alterations and histomorphometrically determined hepatocyte and nuclear areas, perivenular fibrotic rim area, and total amount of fat present in the liver. Four groups of 8 animals each were fed: (1) a nutritionally adequate diet (C); (2) a 36% ethanol-containing (as percent of energy), isocaloric diet (A); (3) a 2% protein-containing, isocaloric diet (PD); and (4) a 36% ethanol, 2% protein-containing, isocaloric diet (A-PD), respectively, following the Lieber-DeCarli model. Ethanol-fed, protein-deficient animals showed the highest liver Fe, and the lowest Zn and Cu values, although differences in liver Zn, Mn, and Cu values were not significantly different between PD and A-PD groups. Statistically significant differences of these parameters were observed between the A and the A-PD groups, and between the A and PD groups, except for liver iron. Except for liver Mn, differences between C and A groups were statistically significant. These alterations correlated with liver fibrosis and steatosis, serum albumin, and weight loss, except for liver Mn, which was not correlated with fibrosis or steatosis. Thus, protein deficiency seems to enhance ethanol-induced liver Fe, Zn, and Cu alterations, whereas protein deficiency, but not ethanol, seems to play a major role on liver Mn alterations.
Assuntos
Cobre/análise , Etanol/toxicidade , Ferro/análise , Fígado/química , Manganês/análise , Deficiência de Proteína/metabolismo , Zinco/análise , Animais , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Ratos , Ratos WistarRESUMO
Alcoholism is related to malnutrition and low levels of several vitamins that take part in the metabolism of homocysteine. The objective of the study was to analyze the prevalence of hyperhomocysteinemia in patients with heavy alcohol intake and the factors on which it depends. Included in the study were 103 hospitalized heavy drinkers (i.e., patients with an intake of alcohol greater than 80 g per day). Serum homocysteine, folate, and vitamin B(12) levels, plasma vitamin B(6) levels, and CT677 polymorphisms of methylenetetrahydrofolate reductase (MTHFR) were determined. We also recorded the intensity of alcoholism, the status of nutrition, and the existence of liver cirrhosis. Determination of biochemical data was repeated after 15 days of withdrawal. Serum homocysteine levels were found to be significantly elevated, whereas serum folate and plasma B(6) levels were significantly decreased. Serum homocysteine levels were significantly higher in those heavy drinkers who showed the TT polymorphism of MTHFR, with a prevalence of hyperhomocysteinemia of 84.2% in the homozygote TT, 54.3% in the heterozygote CT, and 31.6% in the normal CC genotype. Serum homocysteine inversely correlated with serum folate, serum B(12), and plasma B(6) levels. We did not find any relation between serum homocysteine and intensity of alcoholism, nutritional status, or liver cirrhosis. Serum folate levels were significantly decreased in heavy drinkers, mainly depending on irregular feeding and malnutrition. After 15 days of withdrawal, serum homocysteine levels significantly decreased, whereas folate, B(12), and B(6) levels significantly increased. The conclusion is that heavy drinkers show a high prevalence of hyperhomocysteinemia related to low levels of folate, B(6), and B(12) and to the TT polymorphism of MTHFR.
Assuntos
Alcoolismo/enzimologia , Alcoolismo/epidemiologia , Hiper-Homocisteinemia/enzimologia , Hiper-Homocisteinemia/epidemiologia , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/sangue , Adulto , Idoso , Alcoolismo/genética , Análise de Variância , Marcadores Genéticos/genética , Humanos , Hiper-Homocisteinemia/genética , Cirrose Hepática Alcoólica/enzimologia , Cirrose Hepática Alcoólica/epidemiologia , Cirrose Hepática Alcoólica/genética , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2) , Pessoa de Meia-Idade , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Polimorfismo Genético/genética , Desnutrição Proteico-Calórica/enzimologia , Desnutrição Proteico-Calórica/epidemiologia , Desnutrição Proteico-Calórica/genética , Estatísticas não ParamétricasRESUMO
This study was performed to analyze the relative and combined effects of ethanol and protein deficiency on bone histology and mineral metabolism in 4 groups of 7 animals each which were pair-fed during 8 weeks with 1) a nutritionally adequate diet; 2) a 36% (as energy) ethanol containing isocaloric diet; 3) a 2% protein, isocaloric diet; and 4) a 36% ethanol 2% protein isocaloric diet, respectively, following the Lieber-DeCarli model. Another group of five rats were fed ad libitum the control diet. The first and second lumbar vertebrae were removed after sacrifice, and processed for histomorphometrical analysis of undecalcified bone samples. Blood and 24-h urine were also collected. Protein malnutrition, but not ethanol, leads to osteoporosis and reduced osteoid synthesis, whereas ethanol and protein malnutrition both lead to impaired bone mineral apposition and increased urinary hydroxyproline excretion. These changes are accompanied by an increase in serum parathormone and serum 1,25 dihydroxy vitamin D3, a slight hypomagnesemia, hypercalciuria and hyperphosphaturia; protein deficiency plays an independent role in these alterations, whereas both ethanol and protein deficiency exert independent effects on decreasing serum testosterone levels; this last alteration may contribute to the bone changes mentioned before.
Assuntos
Doenças Ósseas Metabólicas/fisiopatologia , Calcificação Fisiológica/efeitos dos fármacos , Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Deficiência de Proteína/fisiopatologia , Animais , Doenças Ósseas Metabólicas/induzido quimicamente , Cálcio/sangue , Cálcio/urina , Corticosterona/sangue , Masculino , Hormônio Paratireóideo/sangue , Deficiência de Proteína/sangue , Ratos , Ratos Sprague-Dawley , Testosterona/sangueRESUMO
To investigate the androgen, weak androgen, estrogen, and gonadotrophin response to clomiphene in alcoholics, we determined in 63 male patients (25 with and 38 without liver cirrhosis) serum testosterone, sexual hormone binding protein (SHBG), dehidroepiandrosterone, androstenedione, LH, FSH, prolactin, and estradiol levels, on the first and the sixth day after admission, and after a course of 8 days of clomiphene 200 mg/day. The same test was performed on 15 healthy volunteers. Cirrhotic patients showed decreased basal testosterone levels and a loss of the circadian rhythm with recovery after clomiphene. Although basal testosterone levels in noncirrhotic alcoholics did not differ from those of the controls, there was a significant improvement after withdrawal. SHBG levels were higher in both groups of alcoholics than in controls, pointing to a worse degree of hypogonadism, because only the free hormone is active. Before the clomiphene test, serum LH and FSH levels were nonsignificantly higher in both groups of alcoholics than in the control group. After clomiphene both LH and FSH increased. Androstenedione and estradiol showed a (parallelism) similar behavior in alcoholic and in cirrhotic groups, showing in both cases higher levels than in the control group, and an increase after clomiphene, perhaps reflecting peripheral conversion of androgens to estrogens. Because clomiphene has no effect on the adrenal cortex, the increase of androstenedione after clomiphene points to its testicular origin (directly or after testosterone conversion) and not to an adrenal one. The highest serum estradiol levels were observed in cirrhotics with ascites or gynecomastia. We have not found any relation between serum hormone levels and alcohol intake nor with nutritional status.
Assuntos
Alcoolismo/complicações , Clomifeno/farmacologia , Hipogonadismo/etiologia , Adulto , Síndrome de Resistência a Andrógenos/etiologia , Androgênios/sangue , Androstenodiona/sangue , Estradiol/sangue , Humanos , Hipogonadismo/sangue , Cirrose Hepática Alcoólica/sangue , Cirrose Hepática Alcoólica/complicações , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Testosterona/sangueRESUMO
The relative contribution of protein deficiency to the altered metabolism of certain trace elements in chronic alcoholics is not well defined, so this study was performed to analyse the relative and combined effects of ethanol and protein deficiency on liver, bone, muscle, and blood cell content of copper, zinc, iron, and manganese, and also on serum levels and urinary and fecal excretion of these elements in four groups of eight animals each that were pair-fed during 8 weeks with a nutritionally adequate diet, a 36% (as energy) ethanol-containing isocaloric diet, a 2% protein isocaloric diet, and a 36% ethanol 2% protein isocaloric diet, respectively, following the Lieber-DeCarli model. Five additional rats were fed ad lib the control diet. Protein malnutrition, but not ethanol, leads to liver zinc depletion. Both ethanol and protein malnutrition cause muscle zinc depletion and increase urinary zinc and manganese excretion, whereas ethanol also increases urinary iron excretion and liver manganese content. No differences were observed regarding copper metabolism.
Assuntos
Etanol/farmacologia , Deficiência de Proteína/metabolismo , Oligoelementos/metabolismo , Animais , Sangue/metabolismo , Osso e Ossos/metabolismo , Cobre/metabolismo , Fezes/química , Ferro/metabolismo , Fígado/metabolismo , Masculino , Manganês/metabolismo , Músculos/metabolismo , Ratos , Ratos Wistar , Oligoelementos/sangue , Oligoelementos/urina , Urina/química , Zinco/metabolismoRESUMO
In the present study we have analyzed the relationship between coagulation inhibitors (antithrombin III, protein C and S, thrombomodulin), liver function impairment, and plasma activity of the endothelium-derived proteins plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) in 27 alcoholic cirrhotic patients and 25 controls. Cirrhotics showed decreased values of all the mentioned parameters except for thrombomodulin, PAI-1, and t-PA. Thrombomodulin and t-PA levels were higher in cirrhotics. No relationship was observed between thrombomodulin and t-PA or PAI-1. Protein C and antithrombin III levels were significantly lower in Child's C patients, whereas no correlation was found between t-PA and thrombomodulin and hepatic function derangement. PAI-1 activity was normal in our patients.
Assuntos
Inibidores dos Fatores de Coagulação Sanguínea/sangue , Cirrose Hepática Alcoólica/sangue , Adulto , Idoso , Antitrombina III/metabolismo , Feminino , Humanos , Cirrose Hepática Alcoólica/classificação , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Proteína C/metabolismo , Proteína S/metabolismo , Trombomodulina/sangue , Ativador de Plasminogênio Tecidual/metabolismoRESUMO
Osteopenia is frequent among alcoholics. Its pathogenesis seems to be multifactorial, including ethanol intake, hormonal changes, liver cirrhosis, and malnutrition. Our objective is to determine the relative role of malnutrition on bone loss. One hundred and eighty-one male alcoholic patients, drinkers of more than 80 g ethanol/day, were included, recording data on the intensity of alcoholism, liver cirrhosis, nutritional assessment based on feeding habits, body mass index (BMI), midarm anthropometrics, subjective nutritional assessment, lean and fat mass by dual energy X-ray absorptiometry (DEXA), serum proteins and insulin growth factor Type I (IGF-I), calcitropic hormones, parathyroid hormone (PTH), osteocalcin 25OHD3, and bone mass assessed by DEXA, which was also performed in 43 healthy controls. Alcoholics showed decreased serum osteocalcin, PTH, 25OHD3, IGF-I, and bone mass. Alcoholics were frequently malnourished with decreased BMI, lean, and fat mass. The loss of bone mass was not related to the alteration of calcitropic hormones, to the intensity of alcoholism, or to the existence of liver cirrhosis, but to malnutrition. For a similar BMI, bone loss was more intense in alcoholics than in controls, especially in those with irregular feeding habits. Although cross-sectional ones, our data suggest that alcoholic osteopenia may be interpreted as a form of nutritional osteoporosis, notwithstanding the influence of other factors.
Assuntos
Alcoolismo/complicações , Composição Corporal , Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/etiologia , Distúrbios Nutricionais/complicações , Absorciometria de Fóton , Adulto , Idoso , Proteínas Sanguíneas/análise , Índice de Massa Corporal , Calcifediol/sangue , Calcitonina/sangue , Etanol/administração & dosagem , Hepatite Alcoólica/complicações , Humanos , Fator de Crescimento Insulin-Like I/análise , Cirrose Hepática Alcoólica/complicações , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação Nutricional , Estado Nutricional , Osteocalcina/sangue , Pancreatite Alcoólica/complicações , Hormônio Paratireóideo/sangueRESUMO
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
Strontium metabolism has attracted considerable interest because of to its interaction with calcium, the bone alterations detected after treatment with strontium, and its potential value as a paleodietary indicator. The effects of ethanol on strontium and barium metabolism-another divalent cation which also accumulates in bone--is largely unknown. Based on this fact, we have determined bone content and fecal and urinary excretion of Ba and Sr in four groups of eight animals each pair-fed for 8 wk with (1) a nutritionally adequate diet, (2) a 36% (as energy) ethanol-containing isocaloric diet, (3) a 2% protein, isocaloric diet, and (4) a 36% ethanol, 2% protein isocaloric diet, following the Lieber-DeCarli model. Five additional rats were fed with the control diet ad libitum. We have found that ethanol tends to decrease and a low protein diet to increase bone strontium content; the decrease in bone strontium in the ethanol-fed rats is accompanied by an increase in the absolute excretion of strontium in urine. Ethanol also decreases bone barium content, but the effect of ethanol on urinary barium excretion is opposite that of strontium, a decrease. Thus, we conclude that ethanol alters both barium and strontium metabolism and bone deposition.