Abstract：
BACKGROUND & AIMS:Dihydroxy bile acids induce a bicarbonate-rich hypercholeresis when secreted into canalicular bile in unconjugated form; the mechanism is cholehepatic shunting. The aim of this study was to identify a xenobiotic that induces hypercholeresis by a similar mechanism. METHODS:Five organic acids (sulindac, ibuprofen, ketoprofen, diclofenac, and norfloxacin) were infused into rats with biliary fistulas. Biliary recovery, bile flow, and biliary bicarbonate were analyzed. Sulindac transport was further characterized using Tr(-) rats (deficient in mrp2, a canalicular transporter for organic anions), the isolated perfused rat liver, and hepatocyte membrane fractions. RESULTS:In biliary fistula rats, sulindac was recovered in bile in unconjugated form and induced hypercholeresis of canalicular origin. Other compounds underwent glucuronidation and were not hypercholeretic. In the isolated liver, sulindac had delayed biliary recovery and induced prolonged choleresis, consistent with a cholehepatic circulation. Sulindac was secreted normally in Tr(-) rats, indicating that its canalicular transport did not require mrp2. In the perfused liver, sulindac inhibited cholyltaurine uptake, and when coinfused with cholyltaurine, induced acute cholestasis. With both basolateral and canalicular membrane fractions, sulindac inhibited cholyltaurine transport competitively. CONCLUSIONS:Sulindac is secreted into bile in unconjugated form by a canalicular bile acid transporter and is absorbed by cholangiocytes, inducing hypercholeresis. At high flux rates, sulindac competitively inhibits canalicular bile salt transport; such inhibition may contribute to the propensity of sulindac to induce cholestasis in patients.
journal_name
Gastroenterologyjournal_title
Gastroenterologyauthors
Bolder U,Trang NV,Hagey LR,Schteingart CD,Ton-Nu HT,Cerrè C,Elferink RP,Hofmann AFdoi
10.1016/s0016-5085(99)70356-2keywords:
subject
Has Abstractpub_date
1999-10-01 00:00:00pages
962-71issue
4eissn
0016-5085issn
1528-0012pii
S0016508599003662journal_volume
117pub_type
杂志文章相关文献
GASTROENTEROLOGY文献大全abstract：:The purpose of this study was to determine whether gamma-hydroxybutyrate provides protection against intestinal ischemia/reperfusion injury and to compare its effect with that of allopurinol and vitamin E. Thirty minutes of total regional ischemia, followed by 3 hours of reperfusion, produced intestinal damage that wa...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1016/0016-5085(90)90982-7
更新日期：1990-09-01 00:00:00
abstract：BACKGROUND & AIMS:Retinoids inhibit growth and induce differentiation in a variety of pancreatic carcinoma cells. The goal of this study was to examine the molecular mechanisms responsible for retinoid sensitivity. METHODS:Anchorage-independent growth was examined in AR42J, DSL-6A/C1, and Capan-2 cells using a human t...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1016/s0016-5085(98)70269-0
更新日期：1998-10-01 00:00:00
abstract：BACKGROUND & AIMS:We assessed the risk of ulcers with low-dose aspirin and the interaction of low-dose aspirin with a COX-2 selective inhibitor in a double-blind trial that compared placebo, low-dose aspirin, rofecoxib + low-dose aspirin, and ibuprofen. METHODS:Osteoarthritis patients > or =50 years of age without ulc...
journal_title：Gastroenterology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1053/j.gastro.2004.05.001
更新日期：2004-08-01 00:00:00
abstract：UNLABELLED:Cerebral evoked potentials provide a technique for evaluation of central nervous processing of information derived from a variety of sensory modalities. Evoked potentials associated with balloon distention of the smooth muscle esophagus were studied in 14 adult volunteers. Stimulation was applied via repeate...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1016/0016-5085(90)90286-a
更新日期：1990-03-01 00:00:00
abstract：:The amount of bile acid excreted via an ileostomy at the end of the ileum should give an estimate of the amount of bile acid transported to the colon. In the present study, 8 patients with ileostomies at the end of the ileum but without disease or resection of the small intestine excreted 1690 +/- 205 mumol/day (mean ...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1016/0016-5085(88)90013-3
更新日期：1988-05-01 00:00:00
abstract：:Short-chain fatty acids are produced in the human colon by bacterial fermentation of dietary fibers and other saccharides escaping absorption in the small bowel. Short-chain fatty acid concentrations were determined together with production rates in 6- and 24-h incubations of intestinal outputs from 56 patients with v...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1016/0016-5085(89)91676-4
更新日期：1989-11-01 00:00:00
abstract：:The possible involvement of tumor necrosis factor-alpha in the pathogenesis of an experimentally induced hepatitis was investigated. Balb/c mice were primed with Propionibacterium acnes to induce the infiltration of mononuclear cells into the liver. Immunohistochemical study showed that most of the accumulated mononuc...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1016/0016-5085(90)90965-4
更新日期：1990-09-01 00:00:00
abstract：BACKGROUND & AIMS:Previous studies indicated that the peptide neurotensin (NT) stimulates Cl(-) secretion in animal small intestinal mucosa in vitro. In this study, we investigated whether NT causes Cl(-) secretion in human colonic mucosa and examined the mechanism of this response. METHODS:Human mucosal preparations ...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1053/gast.2000.9310
更新日期：2000-08-01 00:00:00
abstract：BACKGROUND & AIMS:Chronic stress is associated with visceral hyperalgesia in functional gastrointestinal disorders. We investigated whether corticosterone plays a role in chronic psychological stress-induced visceral hyperalgesia. METHODS:Male rats were subjected to 1-hour water avoidance (WA) stress or subcutaneous c...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1053/j.gastro.2010.11.003
更新日期：2011-02-01 00:00:00
abstract：:Incidence of intrahepatic arteriovenous fistula after needle biopsy of the liver, percutaneous transhepatic cholangiography, and transhepatic catheterization of an intrahepatic bile duct or portal vein, was determined by studying the hepatic arteriograms obtained within 1 month of the transhepatic procedure. An arteri...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：
更新日期：1978-06-01 00:00:00
abstract：BACKGROUND & AIMS:Sigmoidoscopy is an effective screening strategy for colorectal cancer that is not widely used by primary care providers. The aim of this study was to assess the impact of "academic detailing" in the form of an outreach educational seminar combined with implementation of on-site sigmoidoscopy services...
journal_title：Gastroenterology
pub_type： 临床试验,杂志文章
doi：10.1053/gast.1999.0029900304
更新日期：1999-08-01 00:00:00
abstract：:The histamine-storing enterochromaffinlike cells, which are numerous in the oxyntic mucosa of the rat stomach, are known to proliferate in response to long-lasting hypergastrinaemia. In addition, portacaval shunting, which is not associated with elevated serum gastrin, causes an increase in enterochromaffinlike cell d...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1016/0016-5085(90)90948-z
更新日期：1990-09-01 00:00:00
abstract：BACKGROUND & AIMS:Indomethacin impairs liver microsomal monooxygenase activities mediated by cytochrome P450 (CYP). We investigated the inhibition mechanism and the isoform selectivity in vitro and in vivo. METHODS:In an in vitro study, liver microsomes from male Wistar rats were preincubated with indomethacin and a r...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1053/gast.2002.31886
更新日期：2002-03-01 00:00:00
abstract：:Enteroglucagon-containing cells have been maintained in short-term culture, and the morphologic characteristics of these cells and their response to selected agents have been determined. After 48 h in culture the ultrastructural appearance of the enteroglucagon-immunoreactive cells showed evidence of polarization with...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1016/0016-5085(87)90442-2
更新日期：1987-10-01 00:00:00
abstract：BACKGROUND & AIMS:Trinitrobenzene sulfonic acid (TNBS)-induced colitis is a T-helper 1 (Th1) T cell-mediated inflammation that is rapidly reversed by administration of anti-interleukin (IL) 12. This study sought to define the mechanism of this curative effect. METHODS:Cells and tissue from mice with TNBS colitis recei...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1016/s0016-5085(99)70392-6
更新日期：1999-11-01 00:00:00
abstract：BACKGROUND/AIMS:The diagnosis of cholangiocarcinoma in primary sclerosing cholangitis (PSC), even with the use of current imaging techniques and brush cytology, is difficult and particularly important in patients being assessed for liver transplantation. This study investigated the accuracy of serum levels of a combina...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1016/0016-5085(95)90462-x
更新日期：1995-03-01 00:00:00
abstract：:We have recently demonstrated that ritanserin, a serotonin 5-hydroxytryptamine receptor antagonist void of systemic effects, caused a significant reduction of portal pressure in conscious cirrhotic dogs. The mechanism by which ritanserin lowers portal pressure is poorly defined. We investigated the splanchnic and syst...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1016/0016-5085(90)91302-m
更新日期：1990-01-01 00:00:00
abstract：BACKGROUND & AIMS:Regenerating (Reg) gene IV is predominantly expressed in gastrointestinal cells and highly up-regulated in many gastrointestinal malignancies, including colorectal cancer (CRC). Human CRC cells expressing higher levels of Reg IV gene and its protein product (Reg IV) are resistant to conventional thera...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1053/j.gastro.2009.10.050
更新日期：2010-02-01 00:00:00
abstract：BACKGROUND & AIMS:Although restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) substantially reduces the risk of colorectal cancer in patients with inflammatory bowel disease (IBD), subsequent pouch neoplasia can develop. There are few data on the incidence of and risk factors for neoplasia, so there i...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1053/j.gastro.2013.09.047
更新日期：2014-01-01 00:00:00
abstract：BACKGROUND AND AIMS:Antibodies directed against oligomannose sequences alpha-1,3 Man (alpha-1,2 Man alpha-1,2 Man)(n) (n = 1 or 2), termed anti-Saccharomyces cerevisiae antibodies (ASCAs) are markers of Crohn's disease (CD). S. cerevisiae mannan, which expresses these haptens, is used to detect ASCA, but the exact immu...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1053/j.gastro.2006.02.009
更新日期：2006-05-01 00:00:00
abstract：:The enterochromaffinlike cells in the rat stomach are rich in histamine and are thought to be under the influence of gastrin. The effect of sustained endogenous and exogenous hypergastrinemia on the activity and proliferation rate of the enterochromaffinlike cells was studied by determining the histidine decarboxylase...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1016/0016-5085(90)90610-d
更新日期：1990-10-01 00:00:00
abstract：:The purpose of these experiments was to determine the contribution of gastrin to the acid secretory response to eating in healthy human subjects. To simulate the gastric and intestinal phases of eating, a meal was homogenized and then infused into the stomach through a nasogastric tube. At the same time, the cephalic ...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1016/0016-5085(87)90968-1
更新日期：1987-04-01 00:00:00
abstract：BACKGROUND & AIMS:There are no prospective, multicenter, double-blind, placebo-controlled, randomized pharmacologic trials for the treatment of pain-predominant functional gastrointestinal disorders in children. The aim of this study was to evaluate the efficacy of amitriptyline in children with pain-predominant functi...
journal_title：Gastroenterology
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1053/j.gastro.2009.06.060
更新日期：2009-10-01 00:00:00
abstract：:Mucins synthesized in colonic cancer are known to be different from those in the normal colon; however, the biochemical differences between these mucins have not been defined. We have purified mucins from samples of nonneoplastic (normal) human colon and colon cancer and found that the carbohydrate content of the canc...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1016/0016-5085(90)90330-4
更新日期：1990-05-01 00:00:00
abstract：BACKGROUND & AIMS:De novo lipogenesis is believed to be involved in oncogenesis. We investigated the role of aberrant lipid biosynthesis in the pathogenesis of human hepatocellular carcinoma (HCC). METHODS:We evaluated expression of enzymes that regulate lipogenesis in human normal liver tissues and HCC and surroundin...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1053/j.gastro.2010.12.006
更新日期：2011-03-01 00:00:00
abstract：:Detailed porphyrin analysis and additional ultrastructural abnormalities of liver cells are described in a patient with features of Rotor's syndrome. Normal values of porphyrin precursors, delta-aminolevulinic acid and porphobilinogen, and porphyrins were found in plasma, urine, and erythrocytes. However, fecal porphy...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：
更新日期：1981-12-01 00:00:00
abstract：:Intragastric titration, introduced in 1973, has become more popular than in the past and is being applied to the study of gastric secretion under a variety of conditions using NaHCO3 and NaOH as titrant. Physical chemical and technical considerations point to limitations on the conditions under which quantitative resu...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：
更新日期：1979-05-01 00:00:00
abstract：BACKGROUND & AIMS:The mechanisms for tissue regeneration and renewal after acute pancreatitis are not well understood but may involve activation of Notch signaling. To study the effect of Notch signaling ablation during acute experimental pancreatitis, we used a chemical and genetic approach to ablate Notch signaling i...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1053/j.gastro.2007.11.003
更新日期：2008-02-01 00:00:00
abstract：BACKGROUND & AIMS:Early growth response gene-1 (Egr-1) is an important inflammatory transcription factor. We hypothesize that leukocyte-derived Egr-1 plays a key inflammatory role in causing postoperative ileus. METHODS:Wild-type, Egr-1 knockout, and chimera mice (constructed by irradiation followed by injection with ...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1053/j.gastro.2008.05.079
更新日期：2008-09-01 00:00:00
abstract：BACKGROUND & AIMS:Patients with cirrhosis are characterized by a reduced splanchnic vascular resistance and a hyporeactivity to adrenergic vasoconstrictors. So far, their adrenergic splanchnic vascular responsiveness has not been evaluated in vitro. We compared responses to alpha1- and beta2-adrenoceptor stimulation of...
journal_title：Gastroenterology
pub_type： 杂志文章
doi：10.1016/s0016-5085(99)70136-8
更新日期：1999-02-01 00:00:00
