Ductular reaction, cytokeratin 7 positivity, and gamma-glutamyl transferase in multistage hepatocarcinogenesis in rats.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is characterized by multistage formation. The presence of ductular reaction, cytokeratin 7 positivity (PCK7), and increased levels of gamma glutamyltransferase (γGT) has been observed during liver carcinogenesis and contribute to tumor progression. Our goal was to evaluate the ductular reaction in multistage carcinogenesis and to correlate PCK7 and γGT levels with tumor incidence, histological characteristics, liver DNA damage index, and the expression of oxidative stress proteins. HCC was induced in 24 male Wistar rats weighing 145-150 g by chronic and intermittent exposure to 50 or 100 mg/kg diethylnitrosamine (DEN). Six control animals received only vehicle. Blood was collected to determine hepatic enzyme levels. Animals were divided into three groups: control (CO), precancerous lesions (PL), and advanced HCC. Liver samples were obtained for immunohistochemical analyses and the measurement of protein expression. Statistical analyses included Tukey's test and Pearson's correlation analyses. We observed an extensive ductular reaction in advanced HCC and a strong correlation between PCK7 and levels of γGT and the poor prognosis and aggressiveness of HCC. The extent of PCK7 and high γGT levels were associated with overexpression of inducible nitric oxide synthase (iNOS) and heat shock factor protein 1 (HSF-1). However, PCK7 and γGT levels were negatively correlated with protein expression of nuclear factor erythroid 2-related factor 2 (NRF2) and inducible heat shock protein 70 (iHSP70). These findings suggest that ductular reaction is involved in the progression of multistage hepatocarcinogenesis.

Environmental risk factors associated with biliary atresia in Rio Grande do Sul, Brazil

Biliary atresia (BA) seems to be a multifactorial disorder in which environmental factors interact with the patient's genetic constitution. This study aimed to analyze information concerning environmental risk factors associated with BA in southern Brazil. A case-control study with mothers of patients with BA and mothers of patients with cystic fibrosis (CF) was conducted. Inquiry included questions related to exposition to environmental risk factors during the periconceptional and gestational (second and third trimesters) periods. Mothers of BA patients had smoked during pregnancy more frequently in comparison with the mothers of CF patients, but no significant difference was found in a multivariate analysis. There was no between group difference in terms of seasonality, but the multivariate analysis showed a significant difference within the BA group between date of conception in winter compared to other seasons. In conclusion, smoking during pregnancy seemed to increase the risk of BA while date of conception in winter decreased it (AU)

Hypoxic-ischemic gene expression profile in the isolated variant of biliary atresia.

BACKGROUND: Biliary atresia (BA) includes a sclerosing cholangiopathy whose nature is not fully deciphered. Aiming to evaluate the role of an arteriopathy as an etiologic factor in BA, we investigated hypoxia and the correlated angiogenic response in livers from affected patients. METHODS: Gene expression of the molecular axis: hypoxia-inducible factor (HIF)1a, HIF2a and vascular endothelial growth factor A (VEGFA)/VEGFR1, VEGFR2. Liver biopsy specimens collected at exploratory laparotomy of age-matched patients with isolated, cytomegalovirus IgM-negative BA (n = 32) and intrahepatic cholestasis (IHC, n = 9) were evaluated. RESULTS: We observed higher HIF1a and HIF2a expression in BA than in IHC. Paradoxically, VEGFR2, the main target of VEGFA-induced angiogenesis, was underexpressed in BA, and VEGFA was decreased in most BA patients. Patients with the highest expression of HIFs and the lowest VEGFA and VEGFR2 were essentially the same, indicating hypoxia without the necessary angiogenesis. This group included most BA patients and, except for HIF2a, they were older and presented increased bilirubin serum levels. In the highest HIF2a/lowest VEGFR2 subsets, gene expression of the cytokeratin 19, marker of cholangiocyte phenotype, was decreased. CONCLUSION: This study suggests that hypoxia-ischemia is present in the livers of patients with BA, progresses over time and leads to a decreased cholangiocyte mass.

Reversão do diabetes mellitus tipo 2 através da cirurgia bariátrica / Reversal of type 2 diabetes mellitus by bariatric surgery

O diabetes mellitus tipo 2 (DM2) é uma doença crônica de etiologia multifatorial, na qual o pâncreas deixa de produzir insulina ou as células param de responder à insulina que é produzida, fazendo com que a glicose sanguínea não seja absorvida pelas célulasdo organismo. Atualmente, o DM2 é um dos principais problemas de saúde pública, tendo como principal fator de risco a obesidade. Devido aos dados preocupantes e o número de pessoas acometidas crescerem a cada ano, a busca por terapias mais eficientes no controle da doença, como a cirurgia bariátrica, se torna de suma mportância. A perda de peso é parcialmente responsável pela melhora dos pacientessubmetidos a cirurgias por presentarem melhora no quadro glicêmico antes mesmo da redução de peso. A explicação para isto está nas incretinas, hormônios gastrointestinais associados à liberação de insulina, dependente da ingestão de nutrientes. O glucagon like peptídeo 1 é o mais importante das incretinas por suprimir a liberaçãode glucagon, desacelerar o esvaziamento gástrico, melhorar a sensibilidade à insulina, além de reduzir o consumo de alimentos. Após novas descobertas da relação das incretinas, a cirurgia bariátrica se mostra como o caminho mais curto na busca por umacura efetiva do DM2