RESUMO

BACKGROUND: Lactose intolerance is a frequent condition in certain populations. Different methods for diagnosis exist. There is scarce literature regarding Lactose Quick Test (LQT) and concordance with other methods for lactose intolerance diagnosis in children. METHODS: Prospectively, we included children who underwent gastroduodenoscopy for evaluation of abdominal pain. We obtained a duodenal sample for LQT and blood sample for genetic test to evaluate LCT C>T-13910 variant. Later, patients underwent breath test with lactose, to evaluate malabsorption. We evaluated the concordance between the three different tests. KEY RESULTS: We included 46 patients, 56.5% women. Mean age was 13.2 years (range 9-18 years). 66.6% of patients had lactose malabsorption according to breath test; 64.4% were homozygous CC; and 91.3% had hypolactasia (mild or severe) according to LQT. None of the patients with normolactasia had altered breath test. Genetic test had a substantial agreement (k = 0.675) with breath test and fair agreement (k = 0.301) with LQT. LQT had fair agreement (k = 0.348) with breath test. CONCLUSIONS & INFERENCES: Genetic test had better concordance with breath test than LQT to diagnose lactose malabsorption, however, none of the patients with normal LQT had lactose malabsorption. In patients who undergo gastroduodenoscopy to study abdominal pain, it seems reasonable to perform LQT, and, in those with hypolactasia, to perform breath test.

Assuntos

Testes Respiratórios , Testes Genéticos , Genótipo , Lactase/genética , Intolerância à Lactose/diagnóstico , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Intolerância à Lactose/genética , Masculino , Polimorfismo de Nucleotídeo Único

RESUMO

Hepatitis C virus (HCV) is mainly hepatotropic; however, several reports document the presence of genomic viral RNA in extrahepatic sites including peripheral blood mononuclear cells (PBMCs). In this study, the presence of HCV RNA was initially evaluated in the plasma and peripheral blood mononuclear cells (PBMCs) of 53 HCV-infected patients who were treated per protocol. PBMC-associated HCV RNA was detectable in 79% of patients. Early virological response to combined pegylated interferon-α (PegIFN) and ribavirin (RBV) therapy in patients with undetectable levels of PBMCs-associated HCV RNA was 100%, while it was 60% (P = 0.003) in those who had detectable levels of PBMC-associated HCV RNA. A sustained virological response was observed in 35% of patients with detectable PBMC-associated HCV RNA, but was 70% in patients with undetectable levels of PBMC-associated HCV RNA (P = 0.07). In a multivariate analysis incorporating parameters such as HCV genotype, viral load, presence of cirrhosis and absence of PBMC-associated HCV RNA, a significant relationship was observed between the detection of PBMC-associated HCV RNA and the sustained virological response (OR 19.4, 95% CI: 2.1-486.2, P = 0.0061). The association between single nucleotide polymorphism (SNP) in IL28B, known predictor of antiviral therapy outcome, and the occurrence of HCV RNA in PBMC in 84 chronically infected patients was then evaluated. Results suggest that the presence of a G allele in rs8099917, known to associate to a poor response to PegIFN/RBV therapy, also predicts an increased association of HCV RNA with PBMC (OR: 3.564; 95% CI: 1.114-11.40, P = 0.0437).

Assuntos

Hepacivirus/isolamento & purificação , Hepatite C Crônica/genética , Hepatite C Crônica/imunologia , Interleucinas/genética , Leucócitos Mononucleares/virologia , Polimorfismo de Nucleotídeo Único , RNA Viral/isolamento & purificação , Adulto , Idoso , Antivirais/uso terapêutico , Feminino , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferons/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ribavirina/uso terapêutico , Resultado do Tratamento

RESUMO

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 Zucker

RESUMO

BACKGROUND AND AIMS: Biliary lipid absorption by the gall bladder mucosa and the cholesterol content of the gall bladder wall appear to play a role in cholesterol gall stone formation. As the scavenger receptor class B type I (SR- BI) regulates cellular cholesterol uptake, we studied its expression in human and murine gall bladders, its regulation by increased biliary lipid content, and its role in gall stone formation. METHODS AND RESULTS: Using immunohistochemistry, SR-BI was found in the apical domain of human gall bladder epithelial cells. Immunoblotting of isolated membranes from gall bladder epithelial cells showed a specific signal for the 82 kDa SR-BI protein. In C57BL/6 mice, SR-BI was also found in the gall bladder epithelium. Using western blot analysis, an inverse relationship was observed between biliary cholesterol concentration and SR-BI expression in murine gall bladder mucosa. By comparing lithogenic diet fed wild-type and SR-BI deficient mice, gall bladder wall cholesterol content and gall stone formation were not found to be dependent on SR-BI expression. CONCLUSIONS: (i) SR-BI is expressed in both human and murine gall bladder epithelium; (ii) biliary cholesterol hypersecretion is associated with decreased gall bladder SR-BI expression in mice; and (iii) murine SR-BI is not essential in controlling gall bladder wall cholesterol content and gall stone formation during diet induced cholelithiasis.

Assuntos

Antígenos CD36/análise , Colelitíase/metabolismo , Vesícula Biliar/metabolismo , Regulação da Expressão Gênica , Proteínas de Membrana , Receptores Imunológicos , Receptores de Lipoproteínas , Animais , Bile/metabolismo , Western Blotting/métodos , Antígenos CD36/genética , Colelitíase/genética , Colesterol/análise , Regulação para Baixo/genética , Epitélio/metabolismo , Regulação da Expressão Gênica/genética , Humanos , Imuno-Histoquímica/métodos , Metabolismo dos Lipídeos , Camundongos , Camundongos Endogâmicos C57BL , Receptores Depuradores , Receptores Depuradores Classe B

RESUMO

The scavenger receptor class B type I (SR-BI), which is expressed in the liver and intestine, plays a critical role in cholesterol metabolism in rodents. While hepatic SR-BI expression controls high density lipoprotein (HDL) cholesterol metabolism, intestinal SR-BI has been proposed to facilitate cholesterol absorption. To evaluate further the relevance of SR-BI in the enterohepatic circulation of cholesterol and bile salts, we studied biliary lipid secretion, hepatic sterol content and synthesis, bile acid metabolism, fecal neutral sterol excretion, and intestinal cholesterol absorption in SR-BI knockout mice. SR-BI deficiency selectively impaired biliary cholesterol secretion, without concomitant changes in either biliary bile acid or phospholipid secretion. Hepatic total and unesterified cholesterol contents were slightly increased in SR-BI-deficient mice, while sterol synthesis was not significantly changed. Bile acid pool size and composition, as well as fecal bile acid excretion, were not altered in SR-BI knockout mice. Intestinal cholesterol absorption was somewhat increased and fecal sterol excretion was slightly decreased in SR-BI knockout mice relative to controls. These findings establish the critical role of hepatic SR-BI expression in selectively controlling the utilization of HDL cholesterol for biliary secretion. In contrast, SR-BI expression is not essential for intestinal cholesterol absorption.

Assuntos

Ácidos e Sais Biliares/metabolismo , Antígenos CD36/fisiologia , Colesterol/metabolismo , Absorção Intestinal , Fígado/metabolismo , Proteínas de Membrana , Receptores Imunológicos , Receptores de Lipoproteínas , Animais , Northern Blotting , Antígenos CD36/genética , Colesterol/sangue , Masculino , Camundongos , Camundongos Knockout , Receptores Depuradores , Receptores Depuradores Classe B

RESUMO

Chile has one of the highest prevalences of cholesterol gallstone disease in the world. Recent data indicate that this is partly caused by genetic (Indian) factors. However, the causal factors inducing increased gallstone formation have not been elucidated. The aim of this study was to compare biliary composition and cholesterol crystallization in bile from patients of high and moderate risk areas (Chile and The Netherlands) for gallstone disease. Bile was sampled at cholecystectomy from 30 Chilean and 26 Dutch gallstone patients. The Con A-binding fraction (CABF) was extracted from fresh native bile samples by incubation with Con A-sepharose. Reconstitution of the CABF to the Con A-extracted native bile induced almost full recovery of crystallization confirming the validity of this technique. There was no difference between the two groups regarding sex and age. Chilean bile nucleated significantly faster (3.5 +/- 0.6 vs. 7.9 +/- 1.5 days) despite the fact that Dutch bile had a significantly higher cholesterol saturation index (CSI) (1.6 vs. 1.2, P = .01). The total lipid content was not different. Chilean bile contained more total protein (5 vs. 2.9 mg/mL, P = .008). IgG, IgM, Haptoglobin and alpha-1-acid glycoprotein were not different between the two groups. IgA, though, was significantly higher in the Chilean samples (0.44 vs. 0.19 mg/mL, P < .001). Extraction of CABF increased crystal observation time (COT) and decreased crystal growth in both groups. However, the effects were much more pronounced in the Chilean samples. Compared with Dutch bile, Chilean bile crystallizes much faster despite a lower CSI. Chilean bile contains an increased content of Con A-binding nucleation promoting activity.

Assuntos

Bile/metabolismo , Colelitíase/metabolismo , Colesterol/química , Colesterol/metabolismo , Receptores de Concanavalina A/metabolismo , Chile , Colelitíase/etiologia , Cristalização , Cristalografia , Humanos , Países Baixos , Fatores de Risco

RESUMO

Gallbladder cancer is usually associated with gallstone disease, late diagnosis, unsatisfactory treatment, and poor prognosis. We report here the worldwide geographical distribution of gallbladder cancer, review the main etiologic hypotheses, and provide some comments on perspectives for prevention. The highest incidence rate of gallbladder cancer is found among populations of the Andean area, North American Indians, and Mexican Americans. Gallbladder cancer is up to three times higher among women than men in all populations. The highest incidence rates in Europe are found in Poland, the Czech Republic, and Slovakia. Incidence rates in other regions of the world are relatively low. The highest mortality rates are also reported from South America, 3.5-15.5 per 100,000 among Chilean Mapuche Indians, Bolivians, and Chilean Hispanics. Intermediate rates, 3.7 to 9.1 per 100,000, are reported from Peru, Ecuador, Colombia, and Brazil. Mortality rates are low in North America, with the exception of high rates among American Indians in New Mexico (11.3 per 100,000) and among Mexican Americans. The main associated risk factors identified so far include cholelithiasis (especially untreated chronic symptomatic gallstones), obesity, reproductive factors, chronic infections of the gallbladder, and environmental exposure to specific chemicals. These suspected factors likely represent promoters of carcinogenesis. The main limitations of epidemiologic studies on gallbladder cancer are the small sample sizes and specific problems in quantifying exposure to putative risk factors. The natural history of gallbladder disease should be characterized to support the allocation of more resources for early treatment of symptomatic gallbladder disease in high-risk populations. Secondary prevention of gallbladder cancer could be effective if supported by cost-effective studies of prophylactic cholecystectomy among asymptomatic gallstone patients in high-risk areas.

Assuntos

Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/genética , Colelitíase/complicações , Colelitíase/genética , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/prevenção & controle , Humanos , Fatores de Risco

RESUMO

BACKGROUND & AIMS: Sterol carrier protein 2 (SCP-2) enhances sterol cycling and facilitates cholesterol translocation between intracellular organelles and plasma membrane in cultured cells, including hepatocytes. We examined the role of SCP-2 in hepatic cholesterol and lipid trafficking through the sinusoidal and canalicular secretory pathways of the liver in vivo. METHODS: Recombinant adenovirus-mediated SCP-2 gene transfer was used to obtain hepatic overexpression of SCP-2 in C57BL/6 mice. RESULTS: SCP-2 overexpression in the mouse liver resulted in an 8-fold increase of SCP-2 protein levels and determined various effects on lipid metabolism. It decreased high-density lipoprotein cholesterol and increased low-density lipoprotein (LDL) cholesterol concentrations. The expressions of hepatic LDL receptor, apolipoprotein (apo) A-I, apoB, and apoE were decreased. SCP-2 overexpression also increased hepatic cholesterol concentration, associated with decreased cholesterol neosynthesis. Increased biliary cholesterol and bile acid secretion, bile acid pool size, and intestinal cholesterol absorption were also observed. CONCLUSIONS: These results indicate that modulation of SCP-2 expression in the liver determines important modifications on lipoprotein metabolism, hepatic cholesterol synthesis and storage, biliary lipid secretion, bile acid metabolism, and intestinal cholesterol absorption.

Assuntos

Proteínas de Transporte/farmacologia , Metabolismo dos Lipídeos , Circulação Hepática/efeitos dos fármacos , Fígado/metabolismo , Proteínas de Plantas , Esteróis/sangue , Animais , Apolipoproteínas/metabolismo , Bile/metabolismo , Ácidos e Sais Biliares/metabolismo , Proteínas de Transporte/genética , Colesterol/metabolismo , Técnicas de Transferência de Genes , Absorção Intestinal/efeitos dos fármacos , Lipoproteínas LDL/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL

RESUMO

The mitochondrial DNAs (mtDNAs) from individuals belonging to three Chilean tribes, the Mapuche, the Pehuenche, and the Yaghan, were studied both by RFLP analysis and D-loop (control region) sequencing. RFLP analysis showed that 3 individuals (1.3%) belonged to haplogroup A, 19 (8%) to haplogroup B, 102 (43%) to haplogroup C, and 113 (47.7%) to haplogroup D. Among the 73 individuals analyzed by D-loop sequencing, we observed 37 different haplotypes defined by 52 polymorphic sites. Joint analysis of data obtained by RFLP and sequencing methods demonstrated that, regardless of the method of analysis, the mtDNA haplotypes of these three contemporary South American aborigine groups clustered into four main haplogroups, in a way similar to those previously described for other Amerindians. These results further revealed the absence of haplogroup A in both the Mapuche and Yaghan as well as the absence of haplogroup B in the Yaghan. These results suggest that the people of Tierra del Fuego are related to tribes from south-central South America.

Assuntos

DNA Mitocondrial/química , Indígenas Sul-Americanos/genética , Sequência de Bases , Chile , Humanos , Dados de Sequência Molecular , Filogenia , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNA

RESUMO

BACKGROUND & AIMS: Because apolipoprotein E (apoE) is a key cholesterol transport molecule involved in the hepatic uptake of chylomicron cholesterol, it may play a critical role in controlling bile cholesterol elimination and cholesterol gallstone formation induced by dietary cholesterol. To test this hypothesis, we studied biliary lipid secretion and gallstone formation in apoE-deficient mice fed cholesterol-rich diets. METHODS: Bile lipid outputs and gallstone sequence events were analyzed in apoE-deficient mice fed a high-cholesterol diet or a lithogenic diet compared with control animals. RESULTS: A high-cholesterol diet increased biliary cholesterol secretion and gallbladder bile cholesterol concentration in wild-type mice; the increase in bile cholesterol secretion was significantly attenuated in apoE-deficient mice. ApoE knockout mice fed a high-cholesterol lithogenic diet had a markedly lower frequency of gallbladder bile cholesterol crystal and gallstone formation than wild-type mice, which was most likely a result of the decreased cholesterol saturation index found in gallbladder bile of apoE-deficient mice. CONCLUSIONS: These results show that apoE expression is an important factor for regulating both biliary secretion of diet-derived cholesterol as well as diet-induced cholesterol gallstone formation in mice.

Assuntos

Apolipoproteínas E/deficiência , Bile/metabolismo , Colelitíase/prevenção & controle , Colesterol na Dieta/administração & dosagem , Colesterol/metabolismo , Animais , Apolipoproteínas E/genética , Apolipoproteínas E/fisiologia , Ácidos e Sais Biliares/metabolismo , Colelitíase/etiologia , Colesterol/sangue , Colesterol na Dieta/farmacologia , Dieta , Vesícula Biliar/metabolismo , Metabolismo dos Lipídeos , Lipoproteínas/sangue , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout/genética

RESUMO

These studies were undertaken to characterize the role of plasma membrane cholesterol in canalicular secretory functions and hepatocyte integrity against intravenous taurocholate administration. Cholesterol and sphingomyelin concentrations and cholesterol/phospholipid ratios were significantly increased in canalicular membranes of diosgenin-fed rats, suggesting a more resistant structure against solubilization by taurocholate. During taurocholate infusion, control rats had significantly decreased bile flow, whereas diosgenin-fed animals maintained bile flow. Maximal cholesterol output increased by 176% in diosgenin-fed rats, suggesting an increased precursor pool of biliary cholesterol in these animals. Maximal phospholipid output only increased by 43% in diosgenin-fed rats, whereas bile salt output remained at control levels. The kinetics of glutamic oxalacetic transaminase, lactic dehydrogenase, and alkaline phosphatase activities in bile showed a significantly faster release in control than in diosgenin-fed rats. After 30 min of intravenous taurocholate infusion, necrotic hepatocytes were significantly increased in control animals. Preservation of bile secretory functions and hepatocellular cytoprotection by diosgenin against the intravenous infusion of toxic doses of taurocholate was associated with an increased concentration of cholesterol and sphingomyelin in the canalicular membrane. The increase of biliary cholesterol output induced by diosgenin was correlated to the enhanced concentration of cholesterol in the canalicular membrane.

Assuntos

Ácidos e Sais Biliares/toxicidade , Membrana Celular/metabolismo , Colesterol/metabolismo , Fígado/patologia , Esfingomielinas/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Bile/efeitos dos fármacos , Bile/metabolismo , Fracionamento Celular , Diosgenina/farmacologia , Modelos Animais de Doenças , L-Lactato Desidrogenase/metabolismo , Lipídeos/análise , Masculino , Fosfolipídeos/metabolismo , Ratos , Ratos Sprague-Dawley , Ácido Taurocólico/toxicidade

RESUMO

Polymorphisms of cytochrome P450 genes show pronounced interethnic variation and have not been previously studied in the South-Amerindian population, which probably has an Asian origin. Therefore, a similar distribution of allelic and haplotype frequencies of cytochrome P450 genes to Asian populations might be expected in South-Amerindians. We analysed the allelic frequencies and haplotype distribution for CYP2D6, CYP1A1 and CYP2E1 genes in the South-Amerindian population of Chile (Mapuche, n = 84) by Southern blot or polymerase chain reaction-restriction fragment length polymorphism. Similar allelic frequencies and haplotype distribution for the CYP2E1 gene between Mapuches and Asian populations were observed. Frequencies of the two major functional CYP2D6*1 and CYP2D6*2 alleles and the CYP2D6*5 null allele were similar to most populations world-wide. The alleles CYP2D6*3 and *9, absent in Asians, were not found in Mapuches. The CYP2D6*4 allelic group, uncommon in Asian populations, had a low frequency in Mapuches (0.036). However, the CYP2D6*10 allele (Ch1, Ch2 and J), highly frequent in Asians (0.33-0.50), had a very low frequency (0.018) in our study population. In addition, the presence of the common Chinese 44 kb XbaI fragment of CYP2D6 (0.19-0.31 in Asians) was not detected in South-Amerindians. Interestingly, high frequencies for the rare m2 and Val alleles of the CYP1A1 gene were found in Mapuches (0.821 and 0.91, respectively), and the rare Val/m2 haplotype was significantly higher in Mapuches (0.748) than in Asians (0.24) (P < 0.01). The frequency of this haplotype in Mapuches is the highest frequency reported to date. The population studied was in Hardy-Weinberg equilibrium for these polymorphisms. The major differences between Mapuches and Asians were for CYP2D6*10 and CYP1A1 allelic frequencies, as well as the absence of the common Chinese 44 kb XbaI fragment of CYP2D6. These differences might be interpreted as a consequence of genetic drifts caused by a founder effect in the settlement of South-Amerindians, or genetic selection caused by dietary or environmental factors.

Assuntos

Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2E1/genética , Indígenas Sul-Americanos/genética , Polimorfismo Genético , Adulto , Idoso , Povo Asiático/genética , Chile , Frequência do Gene , Humanos , Pessoa de Meia-Idade

RESUMO

BACKGROUND & AIMS: The etiology of cholesterol gallstones is multifactorial, with interactions of genes and the environment. The hypothesis that aborigine cholesterol lithogenic genes are widely spread among Chileans, a population with a high prevalence of gallstones, was tested. METHODS: Medical history and anthropometric measurements were obtained and abdominal ultrasonography was performed in 182 Mapuche Indians, 225 Maoris of Easter Island, and 1584 Hispanics. Blood groups, DNA, lipids, and glucose were analyzed. The Amerindian Admixture Index and mitochondrial DNA (mtDNA) assessed the ethnicity and degree of racial admixture. RESULTS: Amerindian Admixture Index was 0.8 in Mapuches and 0.4 in Hispanics. All Mapuches, 88% of Hispanics, but none of Maoris had Amerindian mtDNA haplotypes. Age- and sex-adjusted global prevalence of gallstone disease was higher in Mapuches (35%) than in Hispanics (27%) and Maoris (21%). Compared with Hispanics, the youngest group of Mapuches had the greatest corrected risk of gallstones: odds ratios of 6.0 in women and 2.3 in men. In contrast, the gallstone risk in Maoris was lower compared with Hispanics: odds ratios of 0.6 for women and 0.5 for men. CONCLUSIONS: Cholesterol lithogenic genes appear widely spread among Chilean Indians and Hispanics. They could determine the early formation of gallstones and explain the high prevalence of gallbladder diseases among some South American populations.

Assuntos

Colelitíase/etnologia , Colelitíase/genética , Colesterol/metabolismo , Hispânico ou Latino/estatística & dados numéricos , Indígenas Sul-Americanos/estatística & dados numéricos , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Adulto , Chile/epidemiologia , Colelitíase/metabolismo , Feminino , Hispânico ou Latino/genética , Humanos , Indígenas Sul-Americanos/genética , Masculino , Pessoa de Meia-Idade , Havaiano Nativo ou Outro Ilhéu do Pacífico/genética , Polinésia/epidemiologia

RESUMO

BACKGROUND & AIMS: Biliary proteins are promoters of cholesterol crystallization in artificial model bile. However, their pathogenic importance for cholesterol precipitation in native gallbladder bile (GB) is uncertain. The aim of this study was to evaluate the significance of biliary lipids and proteins on cholesterol crystal detection time (ChCDT) of GB in patients with gallstones. METHODS: ChCDT and concentrations of lipids, albumin, mucins, aminopeptidase N, alpha1-acid glycoprotein, haptoglobin, and immunoglobulins (Igs) were measured in GB of 92 patients, 52 of whom had cholesterol gallstones. RESULTS: ChCDT was markedly reduced in gallstone patients. Compared with patients without gallstones, they had a significant increase in cholesterol saturation and total protein, albumin, mucin, and IgG biliary concentrations. In univariate analysis, ChCDT of GB was significantly correlated with cholesterol saturation and total lipid, protein, Ig, aminopeptidase N, and alpha1-acid glycoprotein concentrations. However, stepwise logistic regression analysis showed that only cholesterol saturation independently correlated to ChCDT. Gallbladder inflammation correlated with the concentration of Igs, but subtraction of IgG from GB did not modify the ChCDT. CONCLUSIONS: Biliary cholesterol transport and saturation, but not proteins, appear critical for the cholesterol crystallization abnormality observed in native bile from patients with gallstones.

Assuntos

Bile/metabolismo , Colesterol/metabolismo , Vesícula Biliar/metabolismo , Colecistite/metabolismo , Cristalização , Feminino , Glicoproteínas/metabolismo , Humanos , Imunoglobulina G/metabolismo , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Tempo

RESUMO

BACKGROUND: Patients with acute pancreatitis (AP) and a normal gallbladder by standard echographic evaluation may have "occult" gallbladder disease or microlithiasis with recurrent episodes of AP. AIM: To conduct a prospective evaluation of patients with the diagnosis of non-biliary AP in order to detect "occult" gallbladder disease and to compare its clinical presentation with that of biliary AP. PATIENTS AND METHODS: Patients admitted with the diagnosis of AP to a clinical hospital were included in the study. According to an abdominal ultrasound study, patients were classified as having or not cholelithiasis. A duodenal biliary drainage was performed in 15 patients with AP and without gallbladder stones. RESULTS: Patients without cholelithiasis had recurrent AP more often than patients with biliary AP (53 and 3.3% respectively). Excessive alcohol ingestion did not rule out the possibility of biliary etiology. In 6 patients, the analysis of duodenal bile showed cholesterol crystals, and cholecystectomy confirmed the existence of gallbladder disease in 5. All of them remained asymptomatic during a follow-up period of four years. One patient refused surgery, with subsequent development of gallstones and recurrent episodes of AP. In other 4 patients, gallbladder disease was confirmed by percutaneous gallbladder puncture or during cholecystectomy. No recurrence of AP were observed during the follow-up CONCLUSIONS: Microlithiasis or "occult" gallbladder disease accounts for at least 67% of the original "non-biliary" AP. Duodenal bile analysis is a useful and necessary technique for the evaluation of patients with "non-biliary" acute pancreatitis. Careful clinical and echographic follow-up of this subgroup of patients with AP is mandatory.

Assuntos

Colelitíase/complicações , Pancreatite/complicações , Doença Aguda , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/sangue , Estudos Prospectivos , Fatores de Risco , Cálculos da Bexiga Urinária/complicações

RESUMO

Autoimmune hepatitis is an inflammatory liver disease characterized by dense mononuclear cell infiltrate in the portal tract, and serologically by the presence of non-organ and liver-specific autoantibodies and increased levels of gammaglobulins in the absence of a known etiology. Three subgroups of autoimmune hepatitis have been recognized, depending on the nature of the autoantibody present in the serum: Type 1 autoimmune hepatitis, associated with smooth-muscle (SMA) or antinuclear antibody (ANA) seropositivity; type 2, with anti-liver/kidney microsome antibody (anti-LKM1), and type 3, with the absence of ANA, SMA and anti-LKM1 and presence of other autoantibodies such as anti-soluble liver antigen (SLA). Subtypes of chronic autoimmune hepatitis have clinically different features and prognoses. An 8 year old female patient presented mild jaundice of insidious onset. The liver was tender and enlarged. Serologic markers for A, B, C, E, Epstein Barr and cytomegalovirus were negative. The liver biopsy showed a histological picture consistent with chronic active hepatitis. High titers of anti-liver/kidney-microsome antibody were found by indirect immunofluorescence test, and this finding was confirmed by Western blot against specific liver microsome antigens. Therapy with prednisolone induced a clinical and biochemical remission after four weeks. The suspension of therapy under strict medical control produced a rapid relapse of clinical and biochemical features. The reinitiation of prednisolone was successful, and an alternate-day program was started and maintained until 8 months follow-up.

Assuntos

Autoanticorpos/sangue , Anticorpos Anti-Hepatite/sangue , Hepatite Autoimune/imunologia , Criança , Feminino , Humanos

RESUMO

Lately, myeloprolipherative disorders are frequently reported as causes of portal vein thrombosis, probably due to the early detection of latent cases of this condition. We report two patients with portal vein thrombosis that presented with abdominal pain, nausea, vomiting and clinical consequences of portal hypertension such as variceal hemorrhage, splenomegaly and ascites. Diagnosis was made by a CAT scan in one patient and doppler ultrasound in the other. Both patients had high platelet counts and an essential thrombocytosis in the bone marrow.

Assuntos

Oclusão Vascular Mesentérica/complicações , Trombocitose/complicações , Trombose/etiologia , Adulto , Idoso , Diagnóstico Diferencial , Ecocardiografia Doppler , Nutrição Enteral , Feminino , Humanos , Hidroxiureia/uso terapêutico , Oclusão Vascular Mesentérica/diagnóstico , Oclusão Vascular Mesentérica/terapia , Veias Mesentéricas , Mielografia , Contagem de Plaquetas , Veia Porta , Trombocitose/diagnóstico , Trombocitose/terapia , Trombose/diagnóstico , Trombose/terapia , Tomografia Computadorizada por Raios X

RESUMO

Cholesterol is transported both in unilamellar phosphatidylcholine vesicles and in bile salts-mixed micelles in native bile. The vesicular carrier of biliary lipids apparently has a well defined protein profile with a potent cholesterol crystallization-promoting activity. This study was conducted to identify and further characterize these vesicular proteins and to test the effect of isolated vesicular proteins on the cholesterol crystal formation in supersaturated model bile. The results confirmed that proteins are a constant component of highly purified biliary vesicles both in hepatic and gallbladder bile. Immunoglobulins (IgA, IgG and IgM) and albumin are associated to the purified hepatic biliary vesicles. Furthermore, four different hydrophobic glycoproteins with a molecular mass of 130, 114, 86, and 62-67 kDa were isolated. These glycoproteins showed no reactivity with anti-human whole serum or anti-immunoglobulin antibodies, suggesting that these proteins are biliary-specific. Isolated 130, 114 and 62-67 kDa vesicular glycoproteins significantly decreased the cholesterol nucleation time in artificial model bile. We concluded that some, but not all, vesicular-bound hydrophobic glycoproteins have cholesterol pronucleating activity and they may be involved in the pathogenesis of cholesterol gallstone disease.

Assuntos

Bile/metabolismo , Colesterol/metabolismo , Glicoproteínas/isolamento & purificação , Western Blotting , Colelitíase/metabolismo , Cromatografia Líquida , Cristalização , Eletroforese em Gel de Poliacrilamida , Glicoproteínas/metabolismo , Humanos

RESUMO

1. Cholesterol nucleation is a critical step in the formation of cholesterol gallstones. This nucleation takes place after aggregation and fusion of cholesterol-rich biliary vesicles, a process probably modulated by biliary proteins. The present study was conducted to identify specific proteins associated with native cholesterol-rich biliary vesicles and to explore their effect on the cholesterol-nucleation time of supersaturated artificial bile. 2. Hepatic bile was obtained from six patients with cholesterol gallstone disease. Biliary vesicles were isolated by ultracentrifugation and were purified by gel filtration chromatography. A small amount of protein (less than 1% by weight) remained associated with the purified cholesterol-rich biliary vesicles. The electrophoretic profile of these proteins was remarkably similar in all six patients, showing the presence of at least six polypeptides (of molecular mass from 52 to 200 kDa), five of them having carbohydrate residues (except the 52 kDa one). The effect of reconstituted biliary vesicle solutions, containing their specific vesicular proteins, on cholesterol-nucleation time was studied by mixing the vesicle solution with artificial supersaturated bile. A potent cholesterol-pronucleating activity, reflected in a 20-70% reduction in nucleation time, was present in the biliary vesicle solutions compared with control solutions having a similar lipid composition. The pronucleating activity disappeared on heating and was not detected in the micellar fraction containing the major proportion of biliary proteins. 3. These results indicate that cholesterol-rich biliary vesicles containing a unique and defined glycoprotein profile can be isolated and purified from human hepatic bile. The potent cholesterol-pronucleating activity of the biliary vesicles from patients with gallstones was unrelated to their lipid composition or cholesterol content.(ABSTRACT TRUNCATED AT 250 WORDS)

Assuntos

Bile/química , Colelitíase/metabolismo , Colesterol/química , Proteínas de Transporte/isolamento & purificação , Cromatografia em Gel , Cristalização , Eletroforese em Gel de Poliacrilamida , Glicoproteínas/isolamento & purificação , Humanos

RESUMO

Over a year period, 60 of 172 patients presenting with upper gastrointestinal bleeding were treated by endoscopic thermocoagulation. Entry criteria included active bleeding (pulsatile or oozing), a visible vessel, sentinel clot or the presence of a pigmented protuberance at the ulcer crater. Hemostatic therapy was performed using the heat probe. The physical status and risk of the patients was estimated according to the ASA classification. Hemostasis was obtained in 17 of 21 patients with pulsatile bleeding (81%), 30 of 30 patients with oozing (100%) and 18 of 18 patients with a visible vessel or a pigmented protuberance in the lesion (100%). Three patients, older than 70 years of age, died. All had pulsatile bleeding from a deep ulcer located at the posterior-inferior wall of the duodenal bulb. They were classified as ASA III (n = 1) or IV (n = 2) with significant concomitant illness. These results suggest that endoscopic thermocoagulation is an effective treatment of active upper gastrointestinal bleeding, especially useful in a group of high risk patients.

Assuntos

Eletrocoagulação/métodos , Hemorragia Gastrointestinal/terapia , Hemostase Endoscópica/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos