Interleukin-15 and other myokines in chronic alcoholics.

AIMS: Interleukin (IL)-15 is highly expressed in skeletal muscle, where it exerts anabolic effects, increasing protein content in muscle fibres and promoting muscle growth. Alcoholics frequently suffer myopathy. Therefore, we analyse the behaviour of IL-15 (and other myokines, such as IL-6, IL-8 and tumour necrosis factor α (TNF-α)) in alcoholics. METHODS: These myokines and also malondialdehyde (MDA)--a lipid peroxidation product--were determined by radioimmunoanalytic techniques in blood samples of 35 chronic alcoholics and 13 age- and sex-matched controls, and compared with body composition, nutritional status, liver function, amount of ethanol and routine biochemical variables. RESULTS: IL-15, IL-6, TNF-α, IL-8 and MDA were all higher in alcoholics than in controls; MDA and IL-6 were clearly related with liver function impairment and short-term prognosis, whereas IL-15 was higher among those who died and was related to serum bilirubin. No relation was found between IL-15 and lean mass. CONCLUSION: IL-15 levels were higher in alcoholics than in controls, especially among those who died within 18 months after admission. They are not related with muscle mass, intensity of alcoholism or nutritional status, but only with serum bilirubin. IL-6 showed inverse correlations with liver function, intensity of alcoholism, nutritional status, left arm muscle mass and short-term mortality.

Nutritional assessment in alcoholic patients. Its relationship with alcoholic intake, feeding habits, organic complications and social problems.

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.

Lack of relationship between plasma thrombomodulin and portal hypertension in alcoholic liver disease.

The present study was performed to analyze the relationship between portal hypertension and alterations of the endothelium-derived proteins thrombomodulin, plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1), which were determined in plasma samples of 28 alcoholic cirrhotic patients and 46 controls. Although cirrhotics showed lower levels of PAI-1, but higher thrombomodulin and t-PA levels than controls, no relationship was observed between thrombomodulin, t-PA or PAI-1 and portal pressure. Therefore, the hypothesis that splachnic endothelial damage secondary to portal hypertension leads to altered thrombomodulin, t-PA and PAI-1 levels in alcoholic cirrhosis is not supported by the results of this study.

Relative and combined effects of ethanol and protein deficiency on some hair trace elements: lack of relationship with body stores.

This study was performed in order to analyze the relative and combined effects of ethanol and protein deficiency on hair copper, zinc, manganese, and iron content in four groups of seven animals each which were pair-fed during 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, respectively, following the Lieber-DeCarli model, and to analyze the relationship between hair copper, zinc, manganese, and iron content, and the liver and muscle content of these elements. Although there was a trend to higher levels of all the elements analyzed in the the hair of the low-protein fed animals, differences were statistically significant regarding copper and manganese, effects being solely attributable to the low protein diet, not to ethanol. Moreover, hair copper was significantly, inversely related with final weight and weight loss. There were significant relationship between liver zinc and muscle zinc (r = 0.57, p = 0.002), but not between liver or muscle zinc and hair zinc; no correlations were observed between muscle copper and hair copper, nor between liver manganese and hair manganese. An inverse, statistically significant correlation was observed between liver copper and hair copper (r = -0.39, p < 0.05).

Hair zinc and copper in chronic alcoholics.

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.

[Prognostic value of the nutrition status and pro-inflammatory cytokines (IL-1, TNF-alpha and IL-6) in critically ill patients]. / Valor pronóstico del estado de nutrición y de las citoquinas proinflamatorias (IL-1, FNT alpha e IL-6) en pacientes graves.

OBJECTIVE: Prognosis of hospitalized patients depends on the status of nutrition, the intensity of the biologic inflammatory response or acute phase response (APR), triggered by cytokine, and the illness severity. These factors have been shown closely related, as cytokine causes malnutrition and organ failure. AIM: to analyze which of these factors are related to mortality and, by multivariate analysis, which of them have an independent predictive value. METHOD: We include 119 patients admitted to a semi-intensive care unit. Nutritional assessment was performed by mid arm anthropometrics, serum albumin, transferrin, IGF-I, and subjective nutritional evaluation; we also determine acute phase proteins and cytokine IL-1, TNF alpha and IL-6. Severity of illness was assessed by organ failure. The only end point considered was death or survival until discharge of hospital. RESULTS: The following data were related to increased mortality: impaired alimentary habits and nutritional subjective assessment, raised serum levels of IL-6 and neutrophil differential count, decreased lymphocyte count, hemoglobin and serum transferrin levels, a negative PPD and the presence of sepsis, shock or organ failure. At multivariate analysis (stepwise logistic regression) only nutritional variables, sepsis and organ failure data showed an independent predictive value, whereas IL-6 was displaced by organ failure data. CONCLUSION: Regarding prognosis, severity of illness and nutritional status have independent predictive value, whereas IL-6 was displaced, probably because it is closely related to the inflammatory response and to organ failure.

Lead, cadmium and zinc in hair samples: relationship with dietary habits and urban environment.

This study was performed in order to analyze the relationships between hair zinc, lead, and cadmium with the kind of diet consumed (by recall of the diet consumed the previous 14 days), living area (urban or rural), tobacco smoking, and body mass index (BMI) among 419 individuals of the Canary Archipelago. Median values and interquartile range were 43 µg/g (18.50-132.50) for zinc, 4.09 µg/g (2.19-8.38) for lead, and 0.128 µg/g (0.05-0.30) for cadmium. We observed that hair zinc was markedly elevated among those consuming fish more frequently and, to a lesser amount, among those who consumed meat frequently, among those living in urban areas, and among those with BMI over 25 kg/m(2), keeping a significant relationship with BMI. Hair lead was also higher among fish consumers, showed a trend to higher values among inhabitants of urban areas, and was lower among obese individuals. Hair cadmium was higher among those who consumed less vegetables and fruits. By multivariate analysis, introducing the variables meat, fish, and vegetable consumption, urban/rural; sex; age; and BMI values, we observed that fish consumption (beta = 0.15) was the only variable independently associated to higher zinc levels; fish consumption (beta = 0.15) and meat consumption (beta = 0.17) were related to high cadmium levels, whereas meat consumption was significantly associated to higher hair lead levels (beta = 0.15). Therefore, we conclude that hair zinc, cadmium, and lead seem to depend more heavily on dietary habits than on tobacco consumption or living in rural or urban areas.

Changes in cytokine levels during admission and mortality in acute alcoholic hepatitis.

Cytokine levels are raised in acute alcoholic hepatitis. However, there are disparate results regarding the duration of altered plasma levels, and there are also discrepancies about the relation of changes during the first 15 days after admission with short-term (in-hospital) or long-term mortality. In 56 patients with acute alcoholic hepatitis we found that IL-8, IL-4, Interferon-γ (IFN-γ), malondialdehyde and C-reactive protein remained higher in patients than in 18 age- and sex-matched controls at admission, at the 7th day and at the 15th day after admission. Moreover, IL-4 levels (and to a lesser extent, IL-10 and IFN-γ ones) increased along the three determinations. However, comparing patients who died during the admission with those who did not, there were no statistically significant differences, but there was a nearly significant trend for MDA (Z=1.89; p=0.059), with higher levels among those who died. When changes between the first and the second determinations were compared with long-term survival, only IL-8 and IFN-γ showed a relation with mortality. IFN-γ values increased among those who survived and decreased among those who died (p=0.048). IFN-γ values at the first determination also showed a relation with long-term mortality, especially when patients with IFN-γ values in the first quartile were compared with those of the 4th one (log rank=5.64; p=0.018; Breslow=4.64; p=0.031). Besides Interferon-γ, only C-reactive protein showed differences between the first and the 4th quartile regarding mortality (Log rank=4.50; p=0.034; Breslow 4.33; p=0.038). In contrast with other studies, no relation was found between TNF-α or IL-6 and mortality.

Fumador de 49 años con red venosa superficial en tórax y cuello y disfonía / Collateral circulation in thorax and dysphonia in a 49-year old smoker

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Valor pronóstico del estado de nutrición y de las citoquinas proinflamatorias (IL-1, FNTa e IL-6) en pacientes graves / Prognostic value in nutritional assessment and cytokine (IL-1, FNTa e IL-6) in critically ill patients

Objetivo: En el pronóstico del paciente hospitalizado influyen, entre otros factores, el estado de nutrición, la intensidad de la reacción de fase aguda (RFA) y la gravedad de la enfermedad. Estos tres factores están estrechamente interrelacionados: la enfermedad, a través de la RFA mediada por citoquinas, produce desnutrición, más intensa cuanto más grave es la enfermedad. Nuestro objetivo es analizar en que medida los mencionados factores están relacionados con la mortalidad y cuáles de ellos tienen valor predictivo independiente. Método: Se ha estudiado a 119 pacientes ingresados consecutivamente en una unidad de cuidados intermedios, en los que se realizó una valoración nutricional objetiva y subjetiva, determinaciones bioquímicas nutricionales, reactantes de fase aguda y citoquinas IL-1, FNTa e IL-6. La gravedad de la enfermedad se valoró a través de la existencia de insuficiencia de órganos. Se consideró como único punto final el fallecimiento o el alta hospitalaria del paciente. Resultados: Se relacionaron con mayor mortalidad un peor estado de nutrición, tanto los antecedentes de alimentación deficiente, como una peor valoración nutricional subjetiva, la elevación de la IL-6, el aumento del porcentaje de neutrófilos, el descenso de los linfocitos, de la hemoglobina, de la transferrina y la anergia al PPD; también la existencia de alguna de las siguientes complicaciones o insuficiencia de órganos: sepsis, ventilación mecánica, shock, insuficiencia renal aguda y alteraciones de la coagulación. En el análisis multivariante (regresión logística) sólo las variables nutricionales, la existencia de sepsis y los datos de insuficiencia de órganos mostraron valor pronóstico independiente, mientras que la IL-6 era desplazada por los datos de fallo de órganos. Conclusión. De cara al pronóstico, la gravedad de la enfermedad y el estado de nutrición aportan información independiente, mientras que la IL-6 queda desplazada, probablemente debido a su estrecha relación con la respuesta inflamatoria y la existencia de fallo de órganos (AU)