Subjects with chronic liver disease are susceptible to hypovitaminosis A due to several factors. Therefore, identifying patients with vitamin deficiency and a requirement for vitamin supplementation is important. Most studies assessing vitamin A in the context of hepatic disorders are conducted using cirrhotic patients. A cross-sectional study was conducted in 43 non-cirrhotic patients with chronic hepatitis C to evaluate markers of vitamin A status represented by serum retinol, liver retinol, and serum retinol-binding protein levels. We also performed the relative dose-response test, which provides an indirect estimate of hepatic vitamin A reserves. These vitamin A indicators were assessed according to the stage of liver fibrosis using the METAVIR score and the body mass index. The sample study was predominantly composed of male subjects (63%) with mild liver fibrosis (F1). The relative dose-response test was <20% in all subjects, indicating vitamin A sufficiency. Overweight or obese patients had higher serum retinol levels than those with a normal body mass index (2.6 and 1.9 µmol/L, respectively; P<0.01). Subjects with moderate liver fibrosis (F2) showed lower levels of serum retinol (1.9 vs 2.5 µmol/L, P=0.01) and retinol-binding protein levels compared with those with mild fibrosis (F1) (46.3 vs 67.7 µg/mL, P<0.01). These results suggested an effect of being overweight on serum retinol levels. Furthermore, more advanced stages of liver fibrosis were related to a decrease in serum vitamin A levels.

Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility.

Several investigators have identified Epstein-Barr virus (EBV) particles in breast carcinomas, a fact that supports a role for EBV in mammary tumorigenesis. The possible mechanism involved in this process is not clear. The present study was carried out in an attempt to determine whether there is a relationship between latent infection with EBV and p53 and p63 expression in breast carcinomas. Immunohistochemistry developed with 3.3-diaminobenzidine tetrahydrochloride was performed in 85 formalin-fixed paraffin-embedded breast carcinomas using anti-EBV EBNA-1, anti-p63, anti-p53, anti-estrogen receptor (ER) and anti-progesterone receptor (PR) antibodies. The cases were selected to represent each of the various histologic types: intraductal carcinoma (N = 12), grade I invasive ductal carcinoma (N = 15), grade II invasive ductal carcinoma (N = 15), grade III invasive ductal carcinoma (N = 15), tubular carcinoma (N = 8), lobular carcinoma (N = 10), and medullary carcinoma (N = 10). The ductal breast carcinomas were graded I, II and III based on the Scarff-Bloom and Richardson grading system modified by Elston and Ellis. One slide containing at least 1000 neoplastic cells was examined in each case. ER, PR, p63, p53 and EBNA-1 were positive in 60, 40, 11.8, 21.2 and 37.6% of carcinomas, respectively. There was a correlation between EBNA-1 and p63 expression (P < 0.001), but not between EBNA-1 and p53 (P = 0.10). These data suggest a possible role for p63 in the mammary tumorigenesis associated with Epstein-Barr virus infection.

Bradykinin has been reported to act as a growth factor for fibroblasts, mesangial cells and keratinocytes. Recently, we reported that bradykinin augments liver regeneration after partial hepatectomy in rats. Angiotensin-converting enzyme (ACE) is also a powerful bradykinin-degrading enzyme. We have investigated the effect of ACE inhibition by lisinopril on liver regeneration after partial hepatectomy. Adult male Wistar rats underwent 70% partial hepatectomy (PH). The animals received lisinopril at a dose of 1 mg kg body weight-1 day-1, or saline solution, intraperitoneally, for 5 days before hepatectomy, and daily after surgery. Four to six animals from the lisinopril and saline groups were sacrificed at 12, 24, 36, 48, 72, and 120 h after PH. Liver regeneration was evaluated by immunohistochemical staining for proliferating cell nuclear antigen using the PC-10 monoclonal antibody. The value for the lisinopril-treated group was three-fold above the corresponding control at 12 h after PH (P<0.001), remaining elevated at approximately two-fold above control values at 24, 36, 48 (P<0.001), and at 72 h (P<0.01) after PH, but values did not reach statistical difference at 120 h after PH. Plasma ACE activity measured by radioenzymatic assay was significantly higher in the saline group than in the lisinopril-treated group (P<0.001), with 81% ACE inhibition. The present study shows that plasma ACE inhibition enhances liver regeneration after PH in rats. Since it was reported that bradykinin also augments liver regeneration after PH, this may explain the liver growth stimulating effect of ACE inhibitors.

Baseando-se nos efeitos estimuladores do metabolismo energético pelo pré-condicionamento isquêmico (PCI) no tecido hepático, estudou-se dois grupos de ratos cirróticos submetidos a isquemia de 20 min e reperfusão de 120 min, após o PCI ou não respectivamente, determinando assim o valor do seu uso no prolongamento da manobra de Pringle e na regeneração hepática na hepatectomia.

We studied the influence of ischemic preconditioning in rat liver cirrhosis.The cirrhosis were induced in wistar rat with occlusion of biliary duct before 30 days operation and divided into group A, ischemic preconditioning and ischemic/reperfusion, and group B, only ischemic/reperfusion. In group A the preconditioning consisted of 5 min ischemic and 10 min reperfusion. The ischemic/reperfusion consisted of 20 min ischemic and 120 min reperfusion for both groups. The level of respiratory control reason (RCR) in the liver tissue 120 min after reperfusion was not difference significantly in the groups. Therefore it suggests that the preconditioning cam be viability and another object of studies must be rated in future this work.

A modalidade de derivação bílio-digestiva empregada no tratamento da colestase extra-hepática crônica pode influenciar na reparação das lesões hepáticas. Avaliou-se o desempenho das derivações bílio-duodenal e bílio-jejunal em Y de Roux com alça exclusa de diferentes comprimentos na reparação das lesões morfológicas e funcionais do fígado de ratos com fibrose biliar secundária. Foram utilizados ratos Wistar, com 15 dias de obstrução biliar, alocados em 5 grupos de 6 animais. O grupo OB caracterizou as alterações da fibrose biliar. Os animais remanescentes foram tratados mediante derivação com o duodeno (grupo DBD), e com o jejuno, em alça exclusa de 5cm (grupo DBJ5), 10cm (grupo DBJ10) e 15cm (grupo DBJ15), sendo reavaliados 3 meses depois. Outros 6 animais foram submetidos à intervenção simulada e considerados grupo controle (IS). Todos animais foram submetidos à avaliação morfométrica do fígado, análise bioquímica do sangue e microbiológica da bile, estudo da função mitocondrial hepática e verificação do peso úmido do fígado e do baço. Na análise estatística adotou-se o nível de significância de 5%. Houve aumento significativo do peso estimado, em g/Kg de peso corporal, dos ductos biliares, da fibrose e dos hepatócitos nos animais do grupo OB (medianas de 1,30; 10,03 e 37,0) em relação aos animais controles (IS) (medianas de 0,03; zero e 29,37). Após tratamento, ocorreu regressão significativa do peso estimado dos ductos biliares e da fibrose, com valores medianos de 0,22 e 0,22 para o grupo DBD, 0,45 e 3,31 para o grupo DBJ5 e 0,22 e 5,0 para o grupo DBJ15. Houve regressão significativa do peso estimado dos hepatócitos apenas nos grupos derivados com o jejuno, com valores medianos de 31,93; 24,46 e 28,52. Ocorreu aumento significativo do peso úmido do fígado e do baço no grupo OB (medianas em g/Kg de peso corporal de 49,85 e 5,71) em relação ao grupo IS (30,0 e 3,04). Houve regressão significativa do peso do fígado em todos os tratamentos e do peso do baço nos animais tratados com derivação bílio-jejunal, (valores medianos de 35,59 e 2,53 para DBJ5, 37,54 e 2,82 para DBJ10 e 32,73 e 2,93 para DBJ15). Após o tratamento, surgiram infiltrado inflamatório misto, nos espaços portais, refluxo enterobiliar e contaminação bacteriana da bile. Houve aumento significativo no consumo de oxigênio pela mitocôndrias hepáticas nos estados 3 e 4 no grupo OB (medianas de 101,55 e 31,05 nanoátomos de O2/mgprot./min), em relação ao grupo IS (medianas de 57,22 e 15,51). Após o tratamento, normalizou-se o consumo energético apenas nos animais do grupo DBJ15 (medianas de 52,38 e 14,8). O desempenho da derivação bíilio-jejunal indica a importância de avaliar alternativas que possam minimizar o contato do conteúdo entérico com a via biliar.

The type of bile-digestive shunt used for the treatment of cholestasis can be affect the process of repair of liver damage. We evaluated the performance of bile-duodenal and Roux-en-Y bile-jejunal shunts with excluded loop of different lengths in the process of liver repair in rats with secondary biliary fibrosis. Thirty Wistar rats, after 15 days of biliary obstruction (BO), were divided into 5 groups of 6 animals: the BO group, duodenal shunt group (BDS) and with jejunal shunt, with excluded loop of 5 cm (BJS5 group), 10 cm (BJS10 group) and 15 cm (BJS15 group), and reevaluated 3 months later. Six animals were submitted to sham surgery (SHAM group). All animals were submitted to qualitative and morphometric histological evaluations of the liver, to blood biochemical and to microbiological bile analysis, and to a study of hepatic mitochondrial function. Liver and spleen weights (g/kg body weight) were also determined. In the statistical analysis, the level of significance was set at 5%. The animals of the BO group showed a significant increase in median values of total bilirubins (9.6 mg/dl), alkaline phosphatase (AP) (296 U/ml) and aminotransferases (133 U/ml for ALT and 419 U/ml for AST) compared to the SHAM group.with normalization after all the shunt modalities used. A significant increase in liver and spleen weight occurred in the BO group (medians of 49.85 and 5.71, respectively) compared to the SHAM group (medians of 30.0 and 3.04 g/kg). There was a significant regression of liver weight in all the treatments, whereas spleen weight regressed only in the animals treated with a BJS (median values of 2.53 for BJS5, 2.82 for BJS10 and 2.93 for BJS15). There was a significant increase in estimated weight (g/kg body weight) of bile ducts, of fibrosis and of hepatocytes in animals of BO group (medians of 1.30; 10.03 and 37.0, respectively) compared to animals of SHAM group (medians of 0.03; zero and 29.37). There was a significant regression of estimated weight of bile ducts and of fibrosis, with respective median values of 0.22 and 0.22 in BDS group, of 0.45 and 3.31 in BJS5 group, and of 0.22 and 5.0 in BJS15 group. There was a significant regression of estimated hepatocyte weight only in BJS5, BJS10 and BJS15 groups, with median values of 31.93, 24.46 and 28.52 g/kg body weight. In all types of treatment a mixed inflammatory infiltrate occurred in the portal spaces, associated with enterobiliary reflux and with bacterial contamination of the bile. There was a significant increase in oxygen consumption by hepatic mitochondria in states 3 and 4 in BO group (respective medians of 101.55 and 31.05 nanoatoms O2/mg protein/min) compared to SHAM group (medians of 57.22 and 15.51). The O2 consumption normalized only in the animals of BJS15 group (medians of 52.38 and 14.8). The performance of the BJS indicates the importance of the evaluation of alternatives that might minimize the contact of enteric content with the biliary tree.