Urinary excretion of bile acids in bile duct-ligated rats.

BACKGROUND: In patients with complete bile duct obstruction, the only pathway of bile acid elimination is through the urine. However, the urinary excretion of various bile acid conjugates in the presence of bile duct obstruction has not been clarified. Given this factor, the urinary excretion of various bile acids was compared in rats that were bile duct-ligated for 3 days. METHODS: After urinary bladder cannulation, radiolabeled bile acids were intravenously injected, and urine samples were collected every 2 h for 6 h, and radioactivity was counted. RESULTS: Urinary excretion (cumulative percent dose during 6 h) of taurocholate and cholate was similar (19.3% and 16.8%). Urinary excretion of tauroursodeoxycholate, lithocholate, and taurolithocholate-sulfate was less effective (12.7%, 9.8% and 2.1%, respectively). Cholate was mostly conjugated with taurine, and lithocholate was mostly conjugated with taurine and further hydroxylated. CONCLUSIONS: These results indicate that unconjugated bile acids were taken up by the liver and excreted into the blood after further biotransformation even under conditions of complete bile duct obstruction. Although bile acid sulfates are the major bile acids in the urine of patients with obstructive jaundice, monohydroxylated bile acids are considered not to be so effectively excreted into the urine, even with conjugation with taurine and sulfate, in rats.

Involvement of the interferon-gamma-induced T cell-attracting chemokines, interferon-gamma-inducible 10-kd protein (CXCL10) and monokine induced by interferon-gamma (CXCL9), in the salivary gland lesions of patients with Sjögren's syndrome.

OBJECTIVE: To elucidate the mechanism of the development of T cell infiltrates in the salivary glands of patients with Sjögren's syndrome (SS), we studied T cell-attracting chemokines and their receptors. METHODS: The expression of the T cell-attracting chemokines, interferon-gamma (IFNgamma)-inducible 10-kd protein (IP-10; also called CXCL10), monokine induced by IFNgamma (Mig; also called CXCL9), and stromal cell-derived factor 1 (SDF-1; also called CXCL12), in salivary glands from SS patients was investigated by polymerase chain reaction-enzyme-linked immunosorbent assay (ELISA). Cells that produce chemokines and lymphocytes that express chemokine receptors were identified by immunohistochemistry. The production of IP-10 and Mig proteins by salivary epithelial cells in response to IFNgamma was determined by ELISA. RESULTS: Expression of IP-10 and Mig messenger RNA (mRNA) was significantly up-regulated in SS salivary glands compared with normal salivary glands (both P < 0.01). There was no significant difference in SDF-1 mRNA expression between the SS and normal salivary glands. IP-10 and Mig proteins were predominantly expressed in the ductal epithelium adjacent to lymphoid infiltrates. Most of the CD3+ infiltrating lymphocytes in dense periductal foci expressed CXCR3, the receptor for IP-10 and Mig. IFNgamma induced the production of high levels of IP-10 and Mig proteins from cultured SS salivary epithelial cells. CONCLUSION: These findings suggest that IFNgamma stimulates the production of IP-10 and Mig in the SS ductal epithelium, and that IP-10 and Mig are involved in the accumulation of T cell infiltrates in the SS salivary gland. Chemokines or chemokine receptors could be a rational new therapeutic target in SS.

Comparison of urinary excretion of pravastatin and temocapril in bile duct-ligated rats and Eisai hyperbilirubinemic rats (EHBR).

BACKGROUND/PURPOSE: In patients with complete bile duct obstruction, the only pathway for the elimination of cholephilic compounds is through the urine. Although changes in various transporters in the liver and kidney in cholestasis have been elucidated, little is known about how effectively the elimination of these compounds is compensated for by urinary excretion. METHODS: In the present study, the urinary excretion of pravastatin and temocapril was studied in bile-duct-ligated rats (BDLR) for 3 days and in Eisai hyperbilirubinemic rats (EHBR). After urinary bladder cannulation, radiolabeled pravastatin and temocapril were injected intravenously. Urine samples were collected every 1 h for 4 h, and the radioactivity was counted. RESULTS: Urinary excretion of pravastatin was markedly increased in BDLR (85.9% of the dose after 4 h) and moderately increased in EHBR (35.9% of the dose after 4 h) compared with that in control rats (5.5% of the dose after 4 h). Similar but less prominent differences were observed with temocapril after it was administered (50.7%, 38.2%, and 22.0% of the dose after 4 h in BDLR, EHBR, and the controls, respectively). CONCLUSIONS: The absence of biliary excretion of anionic drugs was compensated for by urinary excretion in BDLR and EHBR, and the compensation was more efficient with pravastatin than with temocapril. In patients with complete bile duct obstruction, the only pathway for the elimination of cholephilic compounds is through the urine. Although changes in various transporters in the liver and kidney in cholestasis have been elucidated, little is known about how effectively the elimination of these compounds is compensated for by urinary excretion.

Localization of islet-cell hyperplasia: value of pre- and intraoperative arterial stimulation and venous sampling.

Arterial stimulation and venous sampling was effective in the localization of Beta-cell hyperplasia of the pancreas in the islets of Langerhans in an 84-year-old woman. The patient presented with repeated episodes of unconsciousness and hypoglycemia. She was first suspected of having insulinoma, but diagnostic imaging failed to reveal any tumors. Arterial stimulation and venous sampling (ASVS) and percutaneous transhepatic portal venous sampling (PTPS) were performed to localize the tumor. By ASVS, increases in immuno reactive insulin (IRI) were noted in renal vein blood samples (because a splenorenal shunt was present) after splenic arterial stimulation and venous sampling, and PTPS revealed a stepup in IRI from splenic venous blood samples. Preoperative diagnosis suggested Beta-cell hyperplasia in the pancreas tail. Intraoperative ultrasound failed to find a tumor. Intraoperative ASVS showed the site of increase IRI as the pancreas tail, so distal pancreatectomy and splenectomy were performed. However, hypoglycemia was observed constantly after this operation. Relaparotomy, causing additional resection, was conducted to confirm the precise location and to remove the residual Beta-cell hyperplasia of the pancreas. At the second resection, the existing part of Beta-cell hyperplasia was confirmed through intraoperative ASVS, and additional resection of the pancreas body and neck was performed. At this time, complete removal of the residual Beta-cell hyperplasia was confirmed through ASVS. The hypoglycemia and impaired consciousness disappeared after the operation, and the patient's blood sugar level was maintained at a normal level. Pathological findings revealed islets of Langerhans hyperplasia extending to 1 cm in the pancreas tail region. We conclude that pre- and intraoperative ASVS is a useful test for Beta-cell hyperplasia, which is difficult to diagnose through ordinary imaging techniques.