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Melatonin is a hormone related to circadian rhythms and has potential clinical applications. Our objectives were to verify the effect of melatonin on the liver of zebrafish exposed to fructose and evaluate the expression of appetite-related genes (leptin, ghrelin, and melanocortin receptor 4 [MC4R]). Animals were divided into three groups: control (CG

Aim To evaluate the effects of chronic exposure to ethanol in the liver and the expression of inflammatory genes in zebrafish. Methods Zebrafish (n = 104), wild type, adult, male and female, were divided into two groups: Control and ethanol (0.05 v/v). The ethanol was directly added into water; tanks water were changed every two days and the ethanol replaced. The animals were fed twice a day with fish food until satiety. After two and four weeks of trial, livers were dissected, histological analysis (hematoxilin-eosin and Oil Red staining) and gene expression assessment of adiponectin, adiponectin receptor 2 (adipor2), sirtuin-1 (sirt-1), tumor necrosis factor-alpha (tnf-a), interleukin-1b (il-1b) and interleukin-10 (il-10) were performed. Ultrastructural evaluations were conducted at fourth week. Results Exposing zebrafish to 0.5% ethanol developed intense liver steatosis after four weeks, as demonstrated by oil red staining. In ethanol-treated animals, the main ultrastructural changes were related to cytoplasmic lipid particles and droplets, increased number of rough endoplasmic reticulum cisterns and glycogen particles. Between two and four weeks, hepatic mRNA expression of il-1b, sirt-1 and adipor2 were upregulated, indicating that ethanol triggered signaling molecules which are key elements in both hepatic inflammatory and protective responses. Adiponectin was not detected in the liver of animals exposed and not exposed to ethanol, and il-10 did not show significant difference. Conclusion Data suggest that inflammatory signaling and ultrastructural alterations play a significant role during hepatic steatosis in zebrafish chronically exposed to ethanol.

Introdução: A cirrose caracteriza-se por uma alteração crônica do parênquima hepático que frequentemente leva à desnutrição em crianças e adolescentes. A intervenção nutricional deve ser feita precocemente, o que requer um cuidadoso acompanhamento desses pacientes. Objetivos: Comparar os resultados da avaliação nutricional de crianças e adolescentes cirróticos realizada em dois períodos de tempo distintos. Métodos: Foram utilizados bancos de dados oriundos de duas pesquisas conduzidas com pacientes pediátricos com cirrose. Após a aplicação de critérios de inclusão e exclusão, 67 crianças e adolescentes foram avaliados em duas séries com intervalo de aproximadamente uma década entre elas. As duas séries tiveram as variáveis antropométricas estatura para idade (E/I) e dobra cutânea tricipital para idade (DCT/I) avaliadas de acordo com os padrões da Organização Mundial de Saúde. A gravidade da doença foi avaliada pelos modelos Pediatric End-stage Liver Disease (PELD)/ Model for End-stage Liver Disease (MELD) e pelo escore Child-Pugh. O nível de significância foi estabelecido em 5%. Resultados: Os resultados da avaliação do estado nutricional dos pacientes nas duas séries não mostraram diferença estatisticamente significativa. Na série 1, 22,6% dos pacientes apresentaram desnutrição, e 27,8% na série 2 (p = 0,955). Conclusões: Podemos concluir que nas duas séries avaliadas, separadas por aproximadamente uma década, o percentual de desnutrição e a gravidade da cirrose se mantiveram estáveis. Introduction: Cirrhosis is characterized by a chronic alteration of the liver parenchyma that often leads to malnutrition in children and adolescents. Nutritional intervention should be performed early, requiring careful follow-up of these patients. Objectives: To compare the nutritional assessment of cirrhotic pediatric patients performed in two separate periods of time. Methods: This research used two different databases originated from studies conducted with pediatric patients with cirrhosis. After applying inclusion and exclusion criteria, 67 children and adolescents were assessed in two series of tests performed within a time range of approximately a decade. Both series had standard deviation score for height-for-age (SDS-H/A), standard deviation score for triceps skinfold-for-age and (SDS-TSF/A), calculated according to the standards established by the World Health Organization. Disease severity was evaluated by the Pediatric End-stage Liver Disease (PELD)/Model for End-stage Liver Disease (MELD) and by the Child-Pugh score. Results were considered significant at p < 0.05. Results: The present study did not find any statistically significant difference for the nutritional status of the researched subjects in any of the series. In the first series, 22.6% of patients were undernourished, compared to 27.8% in the second one (p = 0.955). Conclusions: We can conclude that in both series of tests conducted with an interval of about a decade from each other the percentage of malnutrition and the severity of cirrhosis remained stable.

OBJECTIVE To determine plasma zinc concentrations in children and adolescents with cirrhosis and to investigate the association between these results and dietary zinc intake, anthropometric data, and severity of liver disease. METHODS Plasma zinc concentration was assessed by atomic absorption spectrophotometry in 30 children and adolescents with cirrhosis (105.0+/-60.0 months; 22 girls) and 27 without liver disease (122.3+/-47.3 months, 14 girls). Dietary zinc data were evaluated by 3-day food intake records. Anthropometry measures included height, weight, skinfold thickness, brachial circumference, and upper arm muscle size. Severity of liver disease was classified according to the Child-Pugh, MELD, and PELD criteria. RESULTS The mean (+/- standard deviation) plasma zinc concentrations in control subjects and patients were 105.69+/-19.46 and 75.44+/-24.45 microg/dL, respectively (p < 0.001). No associations were found between anthropometric measures, dietary zinc intake, and plasma zinc concentration. There was statistical difference related to plasma zinc concentrations between Child-Pugh B + C patients and control subjects (p < 0.001), and concerning PELD, between patients below the cutoff score of 15 and those above (p = 0.002). CONCLUSIONS The prevalence of hypozincemia was 43% for patients with cirrhosis. Although low plasma zinc concentration was associated with more severe liver disease, it was present even in some Child-Pugh A patients. Therefore, zinc supplementation should be considered for cirrhotic children.

The knowledge that the composition of intestinal microbiota is different in lean and obese humans indicates that the microbiota plays an important role in the pathophysiology of obesity. Studies show that diet composition promotes the modification of intestinal bacterial species, favoring the increase of energy extraction from the diet, insulin resistance and obesity. Unbalanced diets, with overload fat and low fiber content, lead to increased Firmicutes and Proteobacteria phyla favoring dysbiosis, endotoxemia and inflammation. The use of probiotics, prebiotics and symbiotics, in order to modulate the composition of intestinal microbiome, may be a promising therapy for the reduction of the metabolic complications of obesity; however, further studies should be conducted to establish which probiotic species are suitable to help in the treatment of obesity.

Raquel Borges Pinto1, Pedro Eduardo Froehlich2, Ana Claudia Reis Schneider3, Andre Castagna Wortmann3, Tiago Muller Weber2 and Themis Reverbel da Silveira1,* 1Post Graduate Program in Medicine: Pediatrics, 2Post Graduate Program in Pharmaceutical Sciences, UFRGS, Porto Alegre, 3Post Graduate Program in Medical Sciences: Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul (UFRGS), Hospital de Clinicas de Porto Alegre, Brazil

Background Few studies have evaluated abnormalities on brain magnetic resonance imaging (MRI) in children and adolescents with chronic liver disease. Aims The aim of this study was to investigate the presence of T1 hyperintensity in the basal ganglia of pediatric patients with portal hypertension and its association with blood manganese levels. Methods A case control study of 22 patients with portal hypertension (14 Child-Pugh A cirrhosis, 8 non-cirrhotic portal hypertension) and 15 controls was conducted from 2006 to 2007. Blood manganese levels were measured using atomic absorption spectrophotometry. Brain MRI scans were performed using a 1.5 Tesla (Philips) scanner. Results Blood manganese levels were 26.01+/-12.82 microg/L for patients with portal hypertension (cirrhotic: 22.73+/-11.67 microg/L, non-cirrhotic: 32+/-13.32 microg/L) and 15.64+/-6.61 microg/L for controls (p=0.003). 14/22 patients with portal hypertension presented T1 hyperintensity in the basal ganglia [6/14 cirrhotic; 8/8 non-cirrhotic (p=0.018); zero controls (p=0.001)]. Mean blood manganese levels of patients with liver disease and normal vs. abnormal brain MRI scans were 18.45+/-8.38 microg/L and 30.47+/-13.07 microg/L, respectively (p=0.04). Conclusions Brain MRI showed a high frequency (64%) of T1 hyperintensity in the basal ganglia of patients with portal hypertension, which correlated positively with blood manganese levels. This abnormality was found in 100% of the patients with portal hypertension and in 43% of those with mild cirrhotic disease.

OBJETIVO: Determinar a concentração plasmática de zinco em crianças e adolescentes cirróticos e investigar a associação entre esses resultados e a ingestão dietética de zinco, os dados antropométricos e a gravidade da doença hepática. MÉTODOS: As concentrações plasmáticas de zinco foram avaliadas por espectrofotometria de absorção atômica em 30 crianças e adolescentes com cirrose (105,0±60,0 meses; 22 meninas) e 27 hígidas e sem doença hepática (122,3±47,3 meses, 14 meninas). Os dados relacionados ao zinco dietético foram avaliados por registro de ingestão alimentar de 3 dias. A antropometria incluiu peso, altura, espessura da dobra cutânea, circunferência braquial e área muscular do braço. A gravidade da doença hepática foi classificada de acordo com os critérios de Child-Pugh, MELD e PELD. RESULTADOS: As concentrações plasmáticas de zinco dos indivíduos controles e dos pacientes foram 105,69±19,46 e 75,44±24,45 μg/dL, respectivamente (p < 0,001). Nenhuma associação foi encontrada entre os índices antropométricos, a ingestão dietética e o zinco plasmático. Houve diferença estatística nas concentrações de zinco plasmático entre pacientes Child-Pugh B+C e controles (p < 0,001), e com relação ao PELD, entre pacientes abaixo e acima do ponto de corte 15 (p = 0,002). CONCLUSÃO: A prevalência de hipozincemia foi de 43% para pacientes com cirrose. A baixa concentração plasmática de zinco foi associada com a doença hepática grave; entretanto, a hipozincemia esteve presente mesmo em pacientes Child-Pugh A. Portanto, a suplementação de zinco deve ser considerada para os pacientes pediátricos cirróticos. OBJECTIVE: To determine plasma zinc concentrations in children and adolescents with cirrhosis and to investigate the association between these results and dietary zinc intake, anthropometric data, and severity of liver disease. METHODS: Plasma zinc concentration was assessed by atomic absorption spectrophotometry in 30 children and adolescents with cirrhosis (105.0±60.0 months; 22 girls) and 27 without liver disease (122.3±47.3 months, 14 girls). Dietary zinc data were evaluated by 3-day food intake records. Anthropometry measures included height, weight, skinfold thickness, brachial circumference, and upper arm muscle size. Severity of liver disease was classified according to the Child-Pugh, MELD, and PELD criteria. RESULTS: The mean (± standard deviation) plasma zinc concentrations in control subjects and patients were 105.69±19.46 and 75.44±24.45 μg/dL, respectively (p < 0.001). No associations were found between anthropometric measures, dietary zinc intake, and plasma zinc concentration. There was statistical difference related to plasma zinc concentrations between Child-Pugh B + C patients and control subjects (p < 0.001), and concerning PELD, between patients below the cutoff score of 15 and those above (p = 0.002). CONCLUSION: The prevalence of hypozincemia was 43% for patients with cirrhosis. Although low plasma zinc concentration was associated with more severe liver disease, it was present even in some Child-Pugh A patients. Therefore, zinc supplementation should be considered for cirrhotic children.

The malnutrition is a frequent finding in adults with cirrhosis, but the prevalence of nutritional risk and malnutrition is little known in pediatric patients.To evaluate through anthropometry the presence of nutritional risk and malnutrition in cirrhotic pediatric patients regularly attended at the Pediatric Gastroenterology Service of "Hospital de Clínicas" of Porto Alegre, RS, Brazil.Cross-sectional study with 42 cirrhotic children and adolescents aged between 3 months and 18 years. The nutritional evaluation was made by the determination of the weight/age, height/age, body mass index and triceps skinfold thickness and arm muscle circumference measurements. Patients considered in nutritional risk wereor = -1,28 Z score which corresponds toor = 10th percentile, and those under -2,0 Z andor = 3th percentile were in malnutrition status. According to Child-Pugh criteria, 22 patients were classified as A (mild severity), 15 (moderate) B and 5 C (intense).The mean weight/age, height/age and body mass index Z scores were, respectively, - 0,38 +/- 1,4 SD, - 0,83 +/- 1,16 SD and 0,17 +/- 1,3 SD. Patients in nutritional risk were 3/42 (weight/age), 8/42 (height/age), 12/37 (triceps skinfold thickness), 9/37 (arm muscle circumference), 2/38 (body mass index); in malnutrition status were 6/42 (weight/age), 7/42 (height/age), 4/37 (triceps skinfold thickness) and 4/37 (arm muscle circumference) and 3/38 (body mass index).The prevalence of nutritional risk was 32.4% and chronic malnutrition was 16.7%. The index which better reflected the nutritional risk in these patients was triceps skinfold thickness. Chronic malnutrition status occurrence was greater in the height/age index.

RACIONAL: A desnutrição é achado freqüente em adultos com cirrose, mas a prevalência de risco nutricional e de desnutrição é pouco conhecida em pacientes pediátricos. OBJETIVO: Avaliar a ocorrência de risco nutricional e desnutrição em pacientes pediátricos com cirrose atendidos regularmente no Setor de Gastroenterologia Pediátrica do Hospital de Clínicas de Porto Alegre, RS. MÉTODOS: Estudo transversal com 42 crianças e adolescentes cirróticos com idades entre 3 meses e 18 anos. O estado nutricional foi determinado por escores Z de peso para idade, estatura para idade, índice de massa corporal e percentis para a prega cutânea tricipital e circunferência muscular do braço. Consideraram-se pacientes em risco nutricional aqueles com escore

Several conditions, especially chronic liver diseases, can lead to cirrhosis in children and adolescents. Most cases in clinical practice are caused by similar etiologies. In infants, cirrhosis is most often caused by biliary atresia and genetic-metabolic diseases, while in older children, it tends to result from autoimmune hepatitis, Wilson's disease, alpha-1-antitrypsin deficiency and primary sclerosing cholangitis. The symptoms of cirrhosis in children and adolescents are similar to those of adults. However, in pediatric patients, the first sign of cirrhosis is often poor weight gain. The complications of pediatric cirrhosis are similar to those observed in adult patients, and include gastrointestinal bleeding caused by gastroesophageal varices, ascites and spontaneous bacterial peritonitis. In pediatric patients, special attention should be paid to the nutritional alterations caused by cirrhosis, since children and adolescents have higher nutritional requirements for growth and development. Children and adolescents with chronic cholestasis are at risk for several nutritional deficiencies. Malnutrition can have severe consequences for both pre- and post-liver transplant patients. The treatment of cirrhosis-induced portal hypertension in children and adolescents is mostly based on methods developed for adults. The present article will review the diagnostic and differential diagnostic aspects of end-stage liver disease in children, as well as the major treatment options for this condition.

The objective of this work was to develop and fully validate an analytical assay to quantify zinc in hepatic tissue. The procedure should be as simple and fast as possible in order to avoid sample contamination. The amount of sample used should also reflect the sample size usually obtained in clinical biopsies, which are about 3–4 mg at most. The validation protocol is in accordance to international guidelines, such as ICH and FDA. The parameters evaluated were precision, accuracy, range, limit of detection and limit of quantification. The method was evaluated in the 2.0–32.0 parts per billion (μg/l) range. Under the described conditions intra and inter day precision of the three levels of quality controls were lower than 9.06 and 5.27, respectively, expressed as relative standard deviation (RSD). The accuracy ranged from 86.35 to 114.71%. Limit of detection and limit of quantification were 0.60 and 2.0 μg/l, respectively. Fresh bovine liver samples were used in order to evaluate the clinical procedure used to collect biopsies. According to the results and experimental protocol, the method is fully validated and ready to use in clinical trials involving zinc quantitation using hepatic samples as small as 2.00 mg of dry tissue.