Relative and combined effects of ethanol and protein deficiency on bone histology and mineral metabolism.

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.

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)

[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.

[Serum laminin in chronic alcoholic liver disease: its value in the estimation of the degree of fibrosis]. / Laminina sérica en la hepatopatía crónica alcohólica: su valor en la estimación del grado de fibrosis.

AIM: To determine the clinical and prognostic value of serum laminin in chronic alcoholic liver disease and to discern whether laminin, alone or in combination with serum N-terminal type III collagen propeptide, and/or biochemical parameters, is useful in estimating the histomorphometrically determined amount of fibrosis. STUDY DESIGN: Prospective. PATIENTS: 121 (80 of them cirrhotics), 107 followed up for a variable periods ranging from 1 to 1440 days. RESULTS: Serum laminin was higher in cirrhotic patients belonging to Child's C group and, in cirrhotic patients, it significantly correlated with Pugh's score (r = 0.32, p < 0.01), prothrombin activity (r = 0.23, p < 0.05), serum albumin (r = -0.35, p < 0.001) and bilirubin (r = 0.30, p < 0.01), and also with the degree of fibrosis (r = 0.49, p < 0.001). Serum laminin over 3.5 U/ml were associated to higher mortality rates in the total population (Log rank test = 4.9, p = 0.022), but not in cirrhotics. Stepwise multiple regression analysis showed that laminin is useless in the estimation of liver fibrosis in cirrhotics, although in non-cirrhotic alcoholics, serum laminin together with alkaline phosphatase and GGT roughly estimates the amount of liver fibrosis (r = 0.72, p < 0.001, standard error = 7.29). CONCLUSIONS: Laminin is not useful in estimating the total amount of fibrosis neither in prognostic assessment of cirrhotics. However, serum laminin-values over 3.5 U/ml were associated with higher mortality rates in patients with chronic alcoholic liver disease, and serum laminin together with alkaline phosphatase and GGT correlated with the amount of fibrosis in the non-cirrhotic subgroup.

Cytokine levels in acute alcoholic hepatitis: a sequential study.

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.

Serum neopterin levels in alcoholic liver disease.

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.