ABSTRACT
Abstract Purpose: To evaluate the actual incidence of both microlithiasis and acute cholecystitis during treatment with intravenous ceftriaxone in a new rabbit model. Methods: New Zealand rabbits were treated with intravenous ceftriaxone or saline for 21 days. Ultrasound monitoring of the gallbladder was performed every seven days until the 21st day when histopathology, immunohistochemistry for proliferating cell nuclear antigen (PCNA), pro-caspase-3 and CD68, liver enzyme biochemistry, and chromatography analysis of the bile and sediments were also performed. Results: All animals treated with ceftriaxone developed acute cholecystitis, confirmed by histopathology (P<0.05) and biliary microlithiasis, except one that exhibited sediment precipitation. In the group treated with ceftriaxone there was an increase in pro-caspase-3, gamma-glutamyl transpeptidase concentration, PCNA expression and in the number of cells positive for anti-CD68 (P<0.05). In the ceftriaxone group, the cholesterol and lecithin concentrations increased in the bile and a high concentration of ceftriaxone was found in the microlithiasis. Conclusion: Ceftriaxone administered intravenously at therapeutic doses causes a high predisposition for lithogenic bile formation and the development of acute lithiasic cholecystitis.
Subject(s)
Animals , Rats , Ceftriaxone/adverse effects , Cholecystectomy , Cholelithiasis/chemically induced , Cholecystitis, Acute/chemically induced , Anti-Bacterial Agents/adverse effects , Ceftriaxone/administration & dosage , Cholelithiasis/metabolism , Cholecystectomy, Laparoscopic , Cholecystitis, Acute/metabolism , Disease Models, Animal , Translational Research, Biomedical , Administration, Intravenous , Gallbladder/pathology , Anti-Bacterial Agents/administration & dosageABSTRACT
The etiology of biliary tract cancer is obscure, but there are evidences that bile acid plays a role in carcinogenesis. To find the association between biliary tract cancer and bile acid, this study compared the bile acid concentration and composition among patients with biliary cancer, biliary tract stones, and no biliary disease. Bile was compared among patients with biliary tract cancer (n = 26), biliary tract stones (n = 29), and disease free controls (n = 9). Samples were obtained by percutaneous transhepatic biliary drainage, endoscopic nasobiliary drainage, or gallbladder puncture, and analyzed for cholic, deoxycholic, chenodeoxycholic, lithocholic, and ursodeoxycholic acid composition. Total bile acid concentration was lower in the cancer group than the biliary stone and control groups; the proportions of deoxycholic (2.2% vs. 10.2% and 23.6%, p < 0.001 and p < 0.001, respectively) and lithocholic acid (0.3% vs. 0.6% and 1.0%, p = 0.065 and p < 0.001, respectively) were also lower. This result was similar when disease site was limited to bile duct or gallbladder. Analysis of cases with bilirubin < or = 2.0 mg/dL also showed lower total bile acid concentration and deoxycholic acid composition in the cancer group compared to controls (5.7% vs. 23.6%, p = 0.003). Although the presence of bile duct obstruction explains some of the difference in total concentration and composition of bile acid, there are other contributing mechanisms. We suspect the alteration of bile acid transport might decrease bile acid excretion and cause the accumulation of carcinogenic bile acid in bile duct epithelium.
Subject(s)
Middle Aged , Male , Humans , Female , Aged, 80 and over , Aged , Adult , Adolescent , Biomarkers, Tumor/analysis , Gallbladder Neoplasms/metabolism , Cholic Acids/analysis , Cholelithiasis/metabolism , Biliary Tract Neoplasms/chemistryABSTRACT
The etiology of biliary tract cancer is obscure, but there are evidences that bile acid plays a role in carcinogenesis. To find the association between biliary tract cancer and bile acid, this study compared the bile acid concentration and composition among patients with biliary cancer, biliary tract stones, and no biliary disease. Bile was compared among patients with biliary tract cancer (n = 26), biliary tract stones (n = 29), and disease free controls (n = 9). Samples were obtained by percutaneous transhepatic biliary drainage, endoscopic nasobiliary drainage, or gallbladder puncture, and analyzed for cholic, deoxycholic, chenodeoxycholic, lithocholic, and ursodeoxycholic acid composition. Total bile acid concentration was lower in the cancer group than the biliary stone and control groups; the proportions of deoxycholic (2.2% vs. 10.2% and 23.6%, p < 0.001 and p < 0.001, respectively) and lithocholic acid (0.3% vs. 0.6% and 1.0%, p = 0.065 and p < 0.001, respectively) were also lower. This result was similar when disease site was limited to bile duct or gallbladder. Analysis of cases with bilirubin < or = 2.0 mg/dL also showed lower total bile acid concentration and deoxycholic acid composition in the cancer group compared to controls (5.7% vs. 23.6%, p = 0.003). Although the presence of bile duct obstruction explains some of the difference in total concentration and composition of bile acid, there are other contributing mechanisms. We suspect the alteration of bile acid transport might decrease bile acid excretion and cause the accumulation of carcinogenic bile acid in bile duct epithelium.
Subject(s)
Middle Aged , Male , Humans , Female , Aged, 80 and over , Aged , Adult , Adolescent , Biomarkers, Tumor/analysis , Gallbladder Neoplasms/metabolism , Cholic Acids/analysis , Cholelithiasis/metabolism , Biliary Tract Neoplasms/chemistryABSTRACT
Epidemiological studies have shown a positive association between choloesterol gallstones and colonic cancer. These two diseases may be somehow related with bile acids metabolic alterations. The aim of this study was to evaluate the profiles of fecal bile acid in gallstone patients, in order to estimate the quality and amount of fecal bile acids. A fecal bile acid profile of ten gallstone patients and ten controls was compared using high performance liquid chromatography. Total fecal bile acid excretion was significantly increased in gallstone patients compared with controls (692.7 mg/day (302.5-846.2) vs 165.7 mg/day (138.7-221.3), p<0.01) as was the excretion of secondary free bile acids 562.9 mg/day (253.3-704.9) vs 99.9 mg/day (88.9-154.2), p<0.01). Lithocholic and glycodeoxycholic and percentages have also been found to show differences with controls of 55.4 (47.4-73.9) vs 24.6 (22.1-38.4) (p<0.01) and 29.4 (3.3-41.7) vs 2.8 (1.0-3.8) (p<0.03), respectively but deoxycholic acid has not shown differences between the two groups. Moreover, the percentage of ursodeoxycholic acid diminished significantly in gallstone patients (1.5 (1.0-2.8) vs 8.6 (6.0-10.39) (p<0.001), and the decrease of chenodeoxycholic acid was also significant (20.0 (11.4-23.6) vs 8.9 (3.1-10.9) (p<0.03) along with a rise in the rations lithocholic/deoxycholic acids (1.8 (1.4-6.4) vs 0.9 (0.6-1.6) (p<0.05) and glycine/taurine of deoxycholic acid (7.3 (4.1-46.6) vs 0.2 (0.1-0.5) (p<0.01). In conclusion, we have observed a significant increase of total and secondary fecal bile acid excretion as well as a rise of LCA and GDCA percentages and a rise in the ratios of LCA/DCA and glycinet/taurine of DCA.
Subject(s)
Humans , Male , Female , Middle Aged , Adult , Bile Acids and Salts/metabolism , Cholelithiasis/metabolism , Feces/chemistry , Analysis of Variance , Cholelithiasis/complications , Colonic Neoplasms/etiologyABSTRACT
Para avaliar os fatores litogenicos, estudamos retrospectivamente, com relacao a idade, ao sexo, a manifestacao clinicas e antecedentes, cinquenta criancas com nefrolitiase. Todas elas foram submetidas a protocolo prospectivo que constou dos seguintes exames: urina I, urocultura, urinas de 24 horas para dosagem de calcio, acido urico e creatinina, urografia excretora, uretrocistografia miccional, ultra-som renal e prova de sobrecarga oral de calcio. As criancas foram classificadas quanto ao disturbio metabolico conforme criteiros ja estabelecidos. Das cinquenta criancas estudadas apenas 7 (14//) nao apresentaram anormalidade metabolica. Encontramos hipercalciuria renal (HCaR) em 17 (34//); absorvida (HAInt) em 16 (32//); hiperuricosuria (HEAcUr) em 7 (14//) e infeccao dotrato urinario (ITU) em 4 (8//). Observamos um caso de cistinuria. Atraves deste estudo pudemos verificar a importancia da avaliacao metabolica para proposicao de terapeutica especifica para cada caso, principalmente se considerarmos que em 86// das criancas estudadas houve deteccao de alguma, alteracao metabolica
Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Cholelithiasis/metabolism , Acidosis, Renal Tubular , Cystinuria , Bile Duct Diseases , Klebsiella Infections , Proteus Infections , Pseudomonas Infections , Uric AcidABSTRACT
The study was conducted on seventy five patients and thirty controls. The patients were classified into three groups: Group I included patients with gall stones only, Group II included patients with coronary heart disease CHD only and Group III included those with both diseases. Serum levels of the following lipid fractions were estimated: Total cholesterol, phospholipids, tri-glycerides, high density lipoprotein cholesterol, HDL-phospholipids, low density lipo-protein cholesterol and LDL phospholipids. The results showed that the serum total cholesterol was significantly lower in the patients with gall stones compared to controls. The serum phospholipids revealed no difference between patients controls. On the other hand, the serum HDL-cholesterol was significantly lower in all patients than controls. HDL-phospholipids was also lower in the three patient groups in comparison with the controls but this difference is significant in patients with gall stones and in those with CHD. Lastly, the serum level of LDL-cholesterol is significantly higher in all patients than controls LDL phospholipids. The serum level of the LDL-ph was higher in the 3 groups of patients than controls but this difference was significant in Group I and Group III while it was highly significant in Group II compared to controls. The difference between the three groups of patients was insignificant. There is positive correlation in the patient groups and controls as regard the following lipid fractions: Total cholesterol versus phospholipids, total cholesterol versus triglycerides, HDL-cholesterol versus HDL-phospholipids and LDL-cholesterol versus LDL-phospholipids. We had observed that there was no significant difference between the 3 groups of patients in any of the estimated lipid fractions and also in the correlation between the above mentioned parameters, so, we can predict that the metabolic effect and the behaviour of both CHD gall stones are the same. Both the serum total cholesterol and the serum phospholipids have no longer been a determinant factors for either CHD or gall stone disease as thought before. However, the serum levels of the lipoproteins are the good predictive indicators for the development of both diseases
Subject(s)
Lipoproteins/analysis , Cholelithiasis/metabolism , Coronary Disease/metabolism , GallbladderSubject(s)
Humans , Animals , Female , Cholelithiasis/metabolism , Cholesterol/metabolism , Bile/metabolism , Bile , Bile Acids and Salts/metabolism , Bile Acids and Salts , Cholelithiasis/etiology , Cholelithiasis/physiopathology , Cholesterol , Cholesterol/pharmacokinetics , Risk Factors , Lipids/metabolism , LipidsSubject(s)
Adult , Humans , Male , Bile/metabolism , Cholelithiasis/metabolism , Phospholipids , Body Weight , Cholesterol , Bile Acids and Salts , LipidsSubject(s)
Animals , Cholelithiasis/metabolism , Gallbladder/pathology , Glycoproteins/biosynthesis , Hyperplasia , MiceSubject(s)
Adult , Bilirubin/analysis , Calcium/analysis , Cholelithiasis/metabolism , Cholesterol/analysis , Female , Humans , Male , Middle Aged , Proteins/analysisABSTRACT
Numerososa autores han postulado que el mucus presente en la luz de la vesícula biliar sería un factor de importancia en al patogenia de los cálculos biliares. Nuestro trabajo intenta correlacionar la presencia de cálculos con las variaciones citoquímicas que experimenta el epitelio vesicular, pretendiendo lograr alguna información sobre el epitelio biliar alterado y litogénesis. Los estudios realizados indican la presencia de mucosustancias cuya composición difiere en las distintas estucturas celulares de la pared de la vesícula biliar litiásica cuando se compara con vesículas normales. Se pudo determinar que si bien en as vesículas litiásicas se encuentran tanto glicoproteínas como glicosaminglicanos, existe un evidente predominio de glicosaminglicanos ácidos especialmente sulfatados, lo que demuestra que las alteraciones celulares que acompañan a la litiasis implican un cambio de las características citoquímicas de las mucosustancias de las células y secreciones vesiculares