RESUMO
Human Fascioliasis is a zoonosis produced by the liver fluke fasciola. Its diagnosisrequires a high index of suspicion because of the polymorphism in its presentation. However, treatment with triclabendazole is highly effective. We report three cases that, in spite off presenting with diverse clinical severity, all had good response to treatment. Patient 1 presented with nonspecific recurrent abdominal pain with a normal CT scan of abdomen. Patient 2 presented with an abdominal CT scan showing multiple hepatic nodules. Patient 3 with an asymptomatic liver tumor requiring a comprehensive and expensive evaluation. All had eosinophilia and all responded to triclabendazole therapy without adverse effects.
La fasciolasis humana es una zoonosis producida por el trematodo fasciola hepática. Su diagnóstico requiere un alto índice de sospecha dado el polimorfismo en su presentación. Pese a esto, el tratamiento con triclabendazol es muy efectivo. Se reportan tres casos clínicos que, pese a presentar muy distinta clínica y gravedad, todos tuvieron buena respuesta al tratamiento con Triclabendazol. El paciente 1 se presentó con dolor abdominal inespecífico y recurrente, sin compromiso del estado general con tomografía de abdomen normal. La paciente 2 presentó dolor abdominal intenso, baja de peso y gran compromiso del estado general que requirió hospitalización, con tomografía de abdomen que mostró lesiones nodulares hepáticas. La paciente 3 se presentó como hallazgo de tumor hepático asintomático que requirió amplio estudio y grandes costos. Todos presentaron eosinofilia y todos respondieron a terapia con triclabendazol sin efectos adversos.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Fasciolíase/diagnóstico , Fasciolíase/tratamento farmacológico , Anti-Helmínticos/uso terapêutico , Benzimidazóis/uso terapêutico , Fasciola hepaticaRESUMO
BACKGROUND: Obese Zucker rats (ZR) have been used as an experimental model for non-alcoholic fatty liver disease and are particularly susceptible to various types of liver injury. Bile secretory function has not been assessed in ZR. AIM: To study bile secretion and expression of the main hepatobiliary transporters in ZR. METHODS: Bile flow and biliary secretion of lipids and glutathione were determined in eight and 14 week old obese ZR and their lean controls. Protein mass and mRNA of the Na(+)/taurocholate cotransporting polypeptide (Ntcp), the bile salt export pump (Bsep), and the multidrug resistant associated protein 2 (Mrp2) were assessed by western and northern blot, respectively. The effects of administration of a tumour necrosis factor alpha inactivator (etanercept) and an insulin sensitiser (rosiglitazone) were assessed in obese ZR while leptin was given to non-obese rats to study its effect on Mrp2 expression. RESULTS: ZR exhibited increased body weight and hyperlipidaemia. Only 14 week old obese ZR has fatty liver. Decreased bile flow and biliary lipid and glutathione secretion as well as reduced hepatic transport of both taurocholate and bromosulphthalein were found in obese ZR. Hepatic Mrp2 protein mass was markedly reduced (-70%) in obese rats while Ntcp and Bsep protein levels were similar to lean rats. Downregulation of Mrp2 seems to involve both transcriptional and post-transcriptional mechanisms probably related to insulin and leptin resistance. CONCLUSIONS: Obese ZR exhibit an impaired bile secretory function with significant functional and molecular alterations consistent with mild cholestasis. A defective hepatobiliary transport capacity may be a contributory factor in rendering the obese ZR more susceptible to liver injury.
Assuntos
Canalículos Biliares/metabolismo , Bile/metabolismo , Colestase/metabolismo , Obesidade/metabolismo , Animais , Transporte Biológico Ativo , Peso Corporal , Colestase/etiologia , Colestase/patologia , Regulação para Baixo , Fígado/patologia , Masculino , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Obesidade/complicações , Obesidade/patologia , Tamanho do Órgão , RNA Mensageiro/genética , Ratos , Ratos ZuckerRESUMO
Las ciencias biomédicas constituyen el soporte y respaldo científico de la Medicina, por el cual la actividad clínica en todo su espectro, y especialmente en sus acciones diagnósticas y terapéuticas, progresa en lo conceptual, metodológico y técnico. Los avances experimentados por las ciencias biomédicas requieren de médicos-investigadores capacitados para generar nuevo conocimiento relevante, particularmente en enfermedades y problemas de salud prevalentes en nuestro país, tanto en la investigación orientada a la enfermedad, generalmente de carácter más básico, como en la investigación orientada al paciente o clínica y epidemiológica. Los médicos-investigadores son, además, los interlocutores capaces de transferir la nueva información originada en las ciencias básicas a la medicina clínica y de detectar problemas médicos susceptibles de ser investigados a nivel nacional. Sin embargo, estamos asistiendo a una crisis de la investigación en ciencias biomédicas y medicina, que también es pararente en la Gastroenterología, como una importante subespecialidad de la Medicina Interna. Nuestra sociedad aún tiene limitaciones para entender la importancia de la investigación biomédica y clínica y para generar las instancias de formación, especialmente programas de doctorados adecuados y oportunidades laborales atractivas, que incentiven a los estudiantes de Medicina y médicos jóvenes vocacionalmente definidos para asumir la carrera de médico-investigador
Assuntos
Humanos , Gastroenterologia , Pesquisa/estatística & dados numéricos , Pesquisadores , Distribuição por Idade , Chile , Bolsas de Estudo , Projetos de Pesquisa/estatística & dados numéricos , Publicação Periódica/estatística & dados numéricos , Apoio à Pesquisa como AssuntoRESUMO
The canalicular multispecific organic anion transporter, cMoat, is an ATP-binding-cassette protein expressed in the canalicular domain of hepatocytes. In addition to the transport of endo- and xenobiotics, cMoat has also been proposed to transport GSH into bile, the major driving force of bile-acid-independent bile flow. We have shown previously that the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), a peroxisome-proliferator agent, significantly increases bile-acid-independent bile flow in mice. On this basis, the effect of the herbicide on cMoat gene expression was studied. A 3.6-fold increase in cMoat mRNA levels and a 2.5-fold increase in cMoat protein content were observed in the liver of mice fed on a diet supplemented with 0.125% 2,4,5-T. These effects were due to an increased rate of gene transcription (3.9-fold) and were not associated with peroxisome proliferation. Significant increases in bile flow (2.23+/-0.39 versus 1.13+/-0.15 microl/min per g of liver; P<0.05) and biliary GSH output (7.40+/-3.30 versus 2.65+/-0.34 nmol/min per g of liver; P<0.05) were observed in treated animals. The hepatocellular concentration of total glutathione also increased in hepatocytes of treated mice (10.95+/-0.84 versus 5.12+/-0.47 mM; P<0.05), because of the induction (2.4-fold) of the heavy subunit of the gamma-glutamylcysteine synthetase (GCS-HS) gene. This is the first model of co-induction of cMoat and GCS-HS genes in vivo in the mouse liver, associated with increased glutathione synthesis and biliary glutathione output. Our observations are consistent with the hypothesis that the cMoat transporter plays a crucial role in the secretion of biliary GSH.
Assuntos
Ácido 2,4,5-Triclorofenoxiacético/farmacologia , Bile/metabolismo , Proteínas de Transporte/biossíntese , Glutationa/metabolismo , Fígado/efeitos dos fármacos , Animais , Proteínas de Transporte de Ânions , Ânions/metabolismo , Clofibrato/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glutamato-Cisteína Ligase/biossíntese , Herbicidas/farmacologia , Humanos , Fígado/patologia , Masculino , Camundongos , Transcrição Gênica/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
BACKGROUND: The prevalence of chronic pancreatitis in Chile is not known and there is no local information about the surgical treatment of this disease. AIM: To review retrospectively the results of surgical treatment of chronic pancreatitis. MATERIAL AND METHODS: The charts of 17 patients (12 male), aged 7 to 65 years old, with chronic pancreatitis that were operated in three different Chilean regions, were reviewed. RESULTS: Seven patients had previous endoscopic therapeutic procedures (papillotomy in 4 and stent placing in 3). Seven patients had been subjected to previous biliary surgical procedures. Indications for surgery were severe pain in 14 patients, the suspicion of a pancreatic carcinoma in 4 patients, an infected pseudocyst in one and massive bleeding of multiple pseudo-aneurysms in a pseudocyst in one patient. Twelve patients were subjected to decompressions and 5 to pancreatic resections. There was no operative mortality and one transient pancreatic fistula. After an average follow up of 22 months, pain improved in 94% of cases, pancreatic cancer was diagnosed in one patient and 79% of subjects gained weight. One patient became insulin dependent, one increased his insulin requirements and one had transient steatorrhea, since she could not afford pancreatic enzyme replacement therapy. CONCLUSIONS: The multidisciplinary approach of patients with chronic pancreatitis, with selective use of surgery, may greatly improve their quality of life.
Assuntos
Pancreatite/cirurgia , Adolescente , Adulto , Idoso , Criança , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Dor/classificação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The charts of 17 patients (12 male), aged 7 to 65 years old, with chronic pancreatitis that were operated in three different Chilean regions, were reviewed. Results: Seven patients had previous endoscopic therapeutic procedures (papillotomy in 4 and stent placint in 3). Seven patients had been subjected to previous biliary surgical procedures. Indications for surgery were severe pain in 14 patients, the suspicion of a pancreatic carcinoma in 4 patients, an infected pseudocyst in one and massive bleeding of multiple pseudo-aneurysms in a pseudocysts in one patient. Twelve patients were subjected to decompressions and 5 to pancreatic resections. There was no operative mortality and one transient pancreatic fistula. After an average follow up of 22 months, pain improved in 94 percent of cases, pancreatic cancer was diagnosed in one patient and 79 percent of subjects gained weight. One patient became insulin dependent, one increased his insulin requirements and one bad transient steatorrhea, since she could not afford pancreatic enzyme replacement therapy. Conclusions: The multidisciplinary approach of patients with chornic pancreatitis, with selective use of surgery, may greatly improve their quelity of life
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Pancreatectomia , Pancreatite/cirurgia , Pancreatite/complicações , Pancreatite/diagnóstico , Seguimentos , Diabetes Mellitus/etiologia , Doença Crônica , PancreaticojejunostomiaRESUMO
The thrombocytopenia in chronic liver disease (CLD) has been attributed mainly to hypersplenism, although other factors such as reduced mean life span with increased platelet turnover have also been demonstrated. Immunological abnormalities have been described in the pathogenesis and progression of CLD. In this sense, many studies have reported elevated levels of platelet associated IgG (PAIgG) in patients with CLD, and it has been suggested that PAIgG could represent true antiplatelet antibody. In this study we used a glycoprotein (GP)-specific immunoassay (MACE) to determine whether PAIgG or circulating antiplatelet antibodies, reacted against the GPIIb/IIIa or GPIb/IX complexes, in patients with CLD. Thirty-six patients with CLD of diverse etiology were studied (20 female, mean age 53 years, range 38-75 years). 23 out of 36 patients (64%) had anti-GP antibodies in MACE. Particularly, 12 had anti-GPIb, 4 anti-GPIIb/IIIa, and 7 had both types of autoantibodies. The existence of these anti-GP antibodies was not related with the blood platelet count or etiology of CLD. These data show that in patients with CLD of diverse origin, there is a high prevalence of autoantibodies reacting specifically with platelet membrane GP, which constitutes the first evidence of the specific nature of platelet-bound IgG in CLD. These findings suggest that in patients with CLD, an immune mechanism may participate in inducing or aggravating the thrombocytopenia.
Assuntos
Autoanticorpos/imunologia , Plaquetas/imunologia , Hepatopatias/imunologia , Adulto , Idoso , Autoantígenos/imunologia , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Glicoproteínas da Membrana de Plaquetas/imunologiaRESUMO
Cholestasis is associated with a marked increase in the release of canalicular membrane enzymes into bile. This phenomenon has been related to an increased lability of these canalicular membrane integral proteins to the solubilizing effects of secreted bile salts. To further characterize the effects of oral ursodeoxycholic acid (UDCA) administration on ethynylestradiol (EE)-induced cholestasis, the influence of this bile acid on changes in biliary excretion of membrane-bound enzymes was investigated. Bile flow, basal bile salt and biliary lipid secretory rates, the maximum secretory rate of taurocholate (TC SRm), and the biliary excretion of the canalicular membrane-bound ectoenzymes alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) were measured in rats after EE and/or UDCA administration. The activities of ALP, GGT and Na+,K(+)-ATPase in purified isolated canalicular and sinusoidal membrane fractions and the ultrastructure of hepatic acinus, including histochemical studies of ALP distribution, were also examined. EE significantly reduced bile flow, bile salt and biliary lipid secretory rates, and TC SRm, and caused dilatation and loss of microvilli at the canalicular pole of hepatocytes. Biliary excretion of ALP increased 2-fold, whereas biliary excretion of GGT was unchanged. The relationship between biliary excretion of ALP or GGT and bile salt secretion (units of enzyme activity secreted per nanomole of bile salt) was greater in EE-treated rats compared with controls (2.1- and 1.5-fold greater for ALP and GGT, respectively), indicating that in EE-induced cholestasis more enzyme was released into bile per nanomole of bile salt. Na+,K(+)-ATPase activity in sinusoidal membrane fraction was reduced significantly, whereas ALP activity increased in both membrane fractions in EE-treated rats. The histochemical distribution of ALP in the acinus showed a strong reaction in acinar zone 3 and at both the canalicular and sinusoidal membranes. Oral administration of UDCA prevented EE-induced bile secretory failure by normalizing bile flow, bile salt and biliary phospholipid secretory rates, and TC SRm. UDCA also prevented the EE-induced changes in the biliary excretion of enzymes. On the contrary, UDCA did not modify either the enzyme activity in isolated membrane fractions or the morphological or ALP histochemical changes associated with EE administration. These data indicate that in EE-induced cholestasis changes occur at the canalicular membrane, enabling this portion of the plasma membrane to be more susceptible to the solubilizing effect of bile salt, and that oral administration of UDCA prevents bile secretory failure and changes in the biliary excretion of ALP and GGT in EE-treated rats.