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Alterações clínicas e laboratoriais de equinos submetidos à biópsia hepática com agulha Tru-cut guiada por ultrassom

Pós-graduação em Medicina Veterinária - FCAV

Avaliação do polimorfismo genético da lecitina ligante de manose (MBL2) e da expressão gênica dos receptores Toll-Like (TLR) como bio-marcadores do risco cardiovascular em mulheres na pós-menopausa

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação do balanço nitrogenado e aparecimento de nitrogênio uréico como marcadores de catabolismo, infecção e mortalidade em pacientes com lesão renal aguda em diálise

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Avaliação ultrassonográfica hepática ao modo-B, dúplex e tríplex Doppler de cães com sobrepeso e obesos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Protein-energy malnutrition as a consequence of the hospitalization of gastroenterologic patients

The effects of the clinical and dietetics in patient managements on the protein-energy status of hospitalized patients were retrospectively (four yr) investigated in 243 adult (49 +/- 16 yr), male (168) and female (75) patients suffering from chronic liver diseases (42%), intestinal diseases with diarrhea (14%), digestive cancers (11%), chronic pancreatitis (10%), stomach and duodenum diseases (7%), acute pancreatitis (7%), primary protein-energy malnutrition (3%), esophagus diseases (3%), intestinal diseases with constipation 14 (2%) and chronic alcoholism (2%). The protein-energy nutritional status assessed by combinations of anthropometric and blood parameters showed 75% of protein energy malnutrition at the hospital entry mostly (4/5) in severe and moderate grades. The overall average of hospitalization was 20 +/- 15 days being the shortest (13 +/- 5,7 days) for esophagus diseases and the longest (28 +/- 21 days) for the intestinal diseases with diarrhea patients which also received mostly (42%) of the enteral and/or parenteral feedings followed by acute pacreatitis (41%) and digestive cancers (31%) patients. When compared to the entry the protein-energy malnutrition rate at the discharge decreased only 5% despite the increasing of 30% found on the protein-energy intake. The main improvement of the protein-energy nutritional status were attained to those patients showing protein-energy malnutrition milder degrees at the entry which belonged mostly to primary protein-energy malnutrition, acute pancreatitis and intestinal diseases with diarrhea diseases. The later two groups showed protein-energy nutritional status improvement only after the second week of hospitalization. The digestive cancers patients had their protein-energy nutritional status worsened throughout the hospitalization whereas it happened only in the first week for the intestinal diseases with diarrhea and chronic liver diseases patients, improving thereafter up to the discharge. The protein-energy nutritional status improvement found in few patients could be attributed to some complementary factors such as theirs mild degree of protein-energy malnutrition at entry and/or non-invasive propedeutics and/or enteral-parenteral feddings and/or longer hospitalization staying. The institutional causes for the unexpected lack of nutritional responses by the patients were probably the high demand for the few available beds which favour the hospitalization of the most severed patients and the university-teaching pressure for the high rotation of the available beds. Both often resulting in early discharging. In persisting the current physical area and attendance demand one could suggest an aggressive support early at the entry preceding and/or accompanying the more invasive propedeutical procedures.

Avaliação hepática de cães naturalmente infectados por leishmaniose visceral canina: aspectos ultrassonográficos modo B e Doppler

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos do extrato de Agave sisalana Perrine sobre a toxicidade ovariana e uterina, fertilidade e parâmetros fetais de ratas

Pós-graduação em Biociências - FCLAS

Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction in growing animals: immunohistochemical analysis of the expression of TGF-BETA; and VEGF

OBJECTIVE: During the neonatal and infancy periods, some chronic liver diseases may lead to progressive hepatic fibrosis, which is a condition that can ultimately result in the loss of organ function and severe portal hypertension necessitating hepatic transplantation. In a previous report, pharmacological interventions were demonstrated to modulate hepatic fibrosis induced by bile duct ligation in young rats. The administration of pentoxifylline or prednisolone, or the combination of both, resulted in reduced fibrogenesis in portal spaces. The objectives of the present study were to evaluate the expression of transforming growth factor beta and vascular endothelial growth factor after bile duct ligation in young rats and to assess the effect of those same drugs on cytokine expression. METHODS: In this experimental study, 80 young rats (21 or 22 days old) were submitted either to laparotomy and common bile duct ligation or to sham surgery. The animals were allocated into four groups according to surgical procedure, and the following treatments were administered: (1) common bile duct ligation + distilled water, (2) sham surgery + distilled water, (3) common bile duct ligation + pentoxifylline, or (4) common bile duct ligation + prednisolone. After 30 days, a hepatic fragment was collected from each animal for immunohistochemical analysis using monoclonal antibodies against transforming growth factor beta and vascular endothelial growth factor. Digital morphometric and statistical analyses were performed. RESULTS: The administration of pentoxifylline reduced the transforming growth factor beta-marked area and the amount of transforming growth factor beta expressed in liver tissue. This effect was not observed after the administration of prednisolone. There was a significant reduction in vascular endothelial growth factor expression after the administration of either drug compared with the non-treatment group. CONCLUSIONS: The administration of pentoxifylline to cholestatic young rats resulted in the diminished expression of transforming growth factor beta and vascular endothelial growth factor in liver tissue. The administration of steroids resulted in the diminished expression of vascular endothelial growth factor only. These pathways may be involved in hepatic fibrogenesis in young rats submitted to bile duct ligation and exposed to pentoxifylline or prednisolone.

Prevalence of non-organ-specific autoantibodies in a rural community from northeastern Brazil: a population-based study

Non-organ-specific autoantibodies (NOSA) are well-recognized diagnostic markers of autoimmune hepatitis (All-l) and primary biliary cirrhosis (PBC), but can also be observed in patients with viral hepatitis as well as in healthy subjects. The aim of this study was to evaluate the prevalence of NOSA in subjects living in a rural community in Brazil and to correlate their occurrence with the presence of liver disease. Seven hundred twenty-five apparently healthy subjects were randomly selected for assessment of antinuclear (ANA), anti-smooth muscle (SMA), antimitochondrial (AMA), anti-liver/kidney microsome type 1, and anti-liver cytosol type 1 antibodies. Subjects with those NOSA were evaluated for the presence of AIH, PBC, and viral hepatitis. Reactivities for all NOSA, SMA, ANA, and AMA were detected, respectively, in 14, 10, 4, and 0.1% of subjects, with a mean titer of 1:40. NOSA-positive subjects were significantly older and more frequently females. No correlation was observed between the occurrence of NOSA and PBC. AIH, or viral hepatitis. The prevalence of NOSA in Brazilians was 14%. They were usually low titer. NOSA were more frequently observed in females and older subjects and their presence was not correlated with the presence of AIH, PBC, or viral hepatitis. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Clinical findings in patients with GLI2 mutations - phenotypic variability

Mutations in the human GLI2 gene were first reported in association with defective anterior pituitary formation, panhypopituitarism, and forebrain anomalies represented by typical holoprosencephaly (HPE) and holoprosencephaly-like (HPE-L) phenotypes and postaxial polydactyly. Subsequently, anophthalmia plus orbital anomalies, heminasal aplasia, branchial arch anomalies and polydactyly have also been incorporated into the general phenotype. Here we described six Brazilian patients with phenotypic manifestations that range from isolated cleft lip/palate with polydactyly, branchial arch anomalies to semi-lobar holoprosencephaly. Novel sequence variants were found in the GLI2 gene in patients with marked involvement of the temporomandibular joint (TMJ), a new clinical finding observed with mutations of this gene. Clinical, molecular and genetic aspects are discussed.

Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction in growing animals: immunohistochemical analysis of the expression of TGF-β and VEGF

OBJECTIVE: During the neonatal and infancy periods, some chronic liver diseases may lead to progressive hepatic fibrosis, which is a condition that can ultimately result in the loss of organ function and severe portal hypertension necessitating hepatic transplantation. In a previous report, pharmacological interventions were demonstrated to modulate hepatic fibrosis induced by bile duct ligation in young rats. The administration of pentoxifylline or prednisolone, or the combination of both, resulted in reduced fibrogenesis in portal spaces. The objectives of the present study were to evaluate the expression of transforming growth factor β and vascular endothelial growth factor after bile duct ligation in young rats and to assess the effect of those same drugs on cytokine expression. METHODS: In this experimental study, 80 young rats (21 or 22 days old) were submitted either to laparotomy and common bile duct ligation or to sham surgery. The animals were allocated into four groups according to surgical procedure, and the following treatments were administered: (1) common bile duct ligation + distilled water, (2) sham surgery + distilled water, (3) common bile duct ligation + pentoxifylline, or (4) common bile duct ligation + prednisolone. After 30 days, a hepatic fragment was collected from each animal for immunohistochemical analysis using monoclonal antibodies against transforming growth factor β and vascular endothelial growth factor. Digital morphometric and statistical analyses were performed. RESULTS: The administration of pentoxifylline reduced the transforming growth factor β-marked area and the amount of transforming growth factor β expressed in liver tissue. This effect was not observed after the administration of prednisolone. There was a significant reduction in vascular endothelial growth factor expression after the administration of either drug compared with the non-treatment group. CONCLUSIONS: The administration of pentoxifylline to cholestatic young rats resulted in the diminished expression of transforming growth factor β and vascular endothelial growth factor in liver tissue. The administration of steroids resulted in the diminished expression of vascular endothelial growth factor only. These pathways may be involved in hepatic fibrogenesis in young rats submitted to bile duct ligation and exposed to pentoxifylline or prednisolone.

Humoral autoimmune response heterogeneity in the spectrum of primary biliary cirrhosis

Objective To compare autoantibody features in patients with primary biliary cirrhosis (PBC) and individuals presenting antimitochondria antibodies (AMAs) but no clinical or biochemical evidence of disease. Methods A total of 212 AMA-positive serum samples were classified into four groups: PBC (definite PBC, n = 93); PBC/autoimmune disease (AID; PBC plus other AID, n = 37); biochemically normal (BN) individuals (n = 61); and BN/AID (BN plus other AID, n = 21). Samples were tested by indirect immunofluorescence (IIF) on rat kidney (IIF-AMA) and ELISA [antibodies to pyruvate dehydrogenase E2-complex (PDC-E2), gp-210, Sp-100, and CENP-A/B]. AMA isotype was determined by IIF-AMA. Affinity of anti-PDC-E2 IgG was determined by 8 M urea-modified ELISA. Results High-titer IIF-AMA was more frequent in PBC and PBC/AID (57 and 70 %) than in BN and BN/AID samples (23 and 19 %) (p < 0.001). Triple isotype IIF-AMA (IgA/IgM/IgG) was more frequent in PBC and PBC/AID samples (35 and 43 %) than in BN sample (18 %; p = 0.008; p = 0.013, respectively). Anti-PDC-E2 levels were higher in PBC (mean 3.82; 95 % CI 3.36–4.29) and PBC/AID samples (3.89; 3.15–4.63) than in BN (2.43; 1.92–2.94) and BN/AID samples (2.52; 1.54–3.50) (p < 0.001). Anti-PDC-E2 avidity was higher in PBC (mean 64.5 %; 95 % CI 57.5–71.5 %) and PBC/AID samples (66.1 %; 54.4–77.8 %) than in BN samples (39.2 %; 30.9–37.5 %) (p < 0.001). PBC and PBC/AID recognized more cell domains (mitochondria, nuclear envelope, PML/sp-100 bodies, centromere) than BN (p = 0.008) and BN/AID samples (p = 0.002). Three variables were independently associated with established PBC: high-avidity anti-PDC-E2 (OR 4.121; 95 % CI 2.118–8.019); high-titer IIF-AMA (OR 4.890; 2.319–10.314); antibodies to three or more antigenic cell domains (OR 9.414; 1.924–46.060). Conclusion The autoantibody profile was quantitatively and qualitatively more robust in definite PBC as compared with AMA-positive biochemically normal individuals.

Gewebeprotektive und antiinflammatorische Wirkung von humanem Choriogonadotropin in Mausmodellen mit autoimmunem Leberschaden

Während der Schwangerschaft kommt es häufig zu einer spontanen Verbesserung von klinischen Symptomen der autoimmunen Hepatitis und anderen Th1-vermittelten Autoimmunerkrankungen. Die Gründe hierfür sind bis heute noch nicht vollständig aufgeklärt. Eines der wichtigsten Hormone in der Schwangerschaft ist das humane Choriogonadotropin (hCG), welches schon in der frühen Schwangerschaft eine entscheidende Rolle spielt. Es sorgt für die Stimulation des Corpus luteums, wodurch es zur Ausschüttung von Progesteron kommt und somit die Einnistung der Blastozyte gewährleistet und die Abstoßung des Embryos verhindert wird. In dieser Arbeit wurden Effekt und Signalweg von hCG in primären murinen und humanen Hepatozyten sowie in Mausmodellen mit T-Zell-abhängigem Leberschaden untersucht. hCG führte sowohl bei akuten als auch bei chronischen Leberschäden zu einer drastischen Senkung der Aspartat-Aminotransferase, einem Indikator für Lebererkrankungen. Die Histologie der Leber hCG-behandelter Tiere wies außerdem signifikant weniger apoptotische Zellen und eine deutliche Reduktion infiltrierender CD4+ T-Zellen auf. Die Analyse des hCG-Signalweges zeigte, dass hCG die Langlebigkeitsproteine Foxo3a und Sirt1 reguliert. Die Aktivierung des PI3-Kinase/Akt-Signalweges durch hCG führte zu einem Transport des Transkriptionsfaktors Foxo3a aus dem Zellkern, wodurch die proapoptotischen Zielgene Bim und Puma nicht mehr transkribiert werden können. Eine zusätzliche Hemmung von Foxo3a erfolgte durch die Aktivierung der Deacetylase Sirt1, indem diese phosphoryliert wird und in den Zellkern transloziert. In weiteren Untersuchungen wurde der immunsuppressive Effekt von hCG näher betrachtet. Dabei stellte sich heraus, dass hCG effektiv die proteolytische Aktivität der Caspase-3 in Hepatozyten hemmt, wodurch die Ausschüttung der biologisch aktiven Form von Interleukin-16, einem chemotaktischen Faktor für CD4+ Zellen, herabgesetzt wird. Dadurch wird die Leber erfolgreich vor der Infiltration durch autoaggressive CD4+ Zellen geschützt. IL-16 spielt bei vielen inflammatorischen Krankheiten eine Rolle, was auch in dieser Arbeit durch den Nachweis hoher IL-16-Konzentrationen in Seren von Patienten mit autoimmuner Hepatitis bestätigt werden konnte. Die in dieser Studie beschriebene Wirkung von hCG und die Tatsache, dass hCG ein bereits bewährtes und auf Nebenwirkungen getestetes Medikament bei Infertilität ist, macht es zu einem idealen Kandidaten für immunsuppressive Therapieansätze bei akuten und chronisch entzündlichen Lebererkrankungen.

Tumor necrosis factor sensitizes primary murine hepatocytes to Fas/CD95-induced apoptosis in a Bim- and Bid-dependent manner

Fas/CD95 is a critical mediator of cell death in many chronic and acute liver diseases and induces apoptosis in primary hepatocytes in vitro. In contrast, the proinflammatory cytokine tumor necrosis factor α (TNFα) fails to provoke cell death in isolated hepatocytes but has been implicated in hepatocyte apoptosis during liver diseases associated with chronic inflammation. Here we report that TNFα sensitizes primary murine hepatocytes cultured on collagen to Fas ligand (FasL)-induced apoptosis. This synergism is time-dependent and is specifically mediated by TNFα. Fas itself is essential for the sensitization, but neither Fas up-regulation nor endogenous FasL is responsible for this effect. Although FasL is shown to induce Bid-independent apoptosis in hepatocytes cultured on collagen, the sensitizing effect of TNFα is clearly dependent on Bid. Moreover, both c-Jun N-terminal kinase activation and Bim, another B cell lymphoma 2 homology domain 3 (BH3)-only protein, are crucial mediators of TNFα-induced apoptosis sensitization. Bim and Bid activate the mitochondrial amplification loop and induce cytochrome c release, a hallmark of type II apoptosis. The mechanism of TNFα-induced sensitization is supported by a mathematical model that correctly reproduces the biological findings. Finally, our results are physiologically relevant because TNFα also induces sensitivity to agonistic anti-Fas-induced liver damage. CONCLUSION: Our data suggest that TNFα can cooperate with FasL to induce hepatocyte apoptosis by activating the BH3-only proteins Bim and Bid.