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-IdadeRESUMO
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 TempoRESUMO
Several biliary proteins have cholesterol crystallisation promoting activity. One of these glycoproteins is aminopeptidase-N, a canalicular ectoenzyme. This study attempted to localise aminopeptidase-N along the biliary tree, to assess its concentration in a series of 98 patients subjected to abdominal surgery, 40 of them without gall stones, and to correlate its concentration with cholesterol crystal formation time of gall bladder bile. Aminopeptidase-N was isolated from purified native biliary vesicles. A specific polyclonal rabbit anti-aminopeptidase-N antibody was prepared for quantitative immunoblotting and for immunolocalisation. Tissue was obtained from liver biopsy specimens and from gall bladders removed at surgery because of gall stone disease. Aminopeptidase-N was immunolocalised to the apical membranes of hepatocytes and to the apical pole of ductular and gall bladder mucosal cells. The nucleation time of gall bladder bile was mean (SD) 4 (3) days in the gall stone group, compared with 21 (18) days in the control group (p < 0.001). Total absolute biliary protein and aminopeptidase-N concentrations were similar in both the control and gall stone patients. There was a reciprocal significant correlation, however, between the nucleation time and the relative aminopeptidase-N concentration (r = -0.35, p < 0.01) only in the gall stone group of patients. This study shows that this apical transmembrane ectoenzyme with cholesterol crystallisation promoting activity is present along the biliary tree and the hepatocyte. These findings support the concept that high concentrations or qualitative changes of biliary aminopeptidase-N contribute to cholesterol gall stone formation.
Assuntos
Bile/enzimologia , Antígenos CD13/metabolismo , Colelitíase/metabolismo , Colesterol/química , Adulto , Antígenos CD13/análise , Colelitíase/enzimologia , Cristalização , Feminino , Humanos , Imuno-Histoquímica , Fígado/enzimologia , MasculinoRESUMO
The management of rectal and colonic polyps has changed since the advent of endoscopic polypectomy, that interrupts the adenoma-carcinoma sequence. We assessed the effectiveness, limitations, morbidity and mortality of endoscopic polypectomy in 49 polyps larger than 2 cm in diameter. Polypectomy was successful in 94% of polyps, which were predominantly located in left colon (92%) and were pedunculated (87%). A malignant component was found in 28.3% of polyps, that was observed with higher frequency in larger and sessile polyps and in male patients. There was no mortality and scarce morbidity related to the procedure. It is concluded that polypectomy is a low risk procedure that can be frequently performed in ambulatory patients and that endoscopists must suspect malignancy in polyps larger than 2 cm in diameter.
Assuntos
Pólipos do Colo/cirurgia , Pólipos Intestinais/cirurgia , Neoplasias Retais/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Colonoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Se analiza una serie de 152 pacientes operados por lesiones abdominales causadas por arma de fuego. La totalidad de los casos presentaron lesiones múltiples. El intestino delgado y el colon fueron los órganos más frecuentemente afectados. En el manejo de la lesión de colon se aconseja realizar una colostomía, ya que se asocia a menor morbilidad. Las complicaciones sépticas fueron las más frecuentes, tanto de herida operatorio como colecciones intraabdominales. Todos los pacientes fallecidos tenían tres o más órganos comprometidos. La causa de muerte fue una complicación séptica en todos los casos. La baja mortalidad de esta serie es el reflejo de un enfoque quirúrgico agresivo y precoz