Multiple alterations of canalicular membrane transport activities in rats with CCl(4)-induced hepatic injury.

The influence of CCl(4)-induced experimental hepatic injury (CCl(4)-EHI) on the expression and transport activities of primary active transporters on the canalicular membrane, including P-glycoprotein (P-gp), a bile salt export pump (Bsep) and a multidrug resistance associated protein2 (Mrp2), was assessed. CCl(4)-EHI was induced by an intraperitoneal injection of CCl(4) to rats at a dose of 1 ml/kg 24 h prior to the preparation of canalicular liver plasma membrane (cLPM) vesicles and pharmacokinetic studies. The expression of each transporter was measured for the vesicles via Western blot analysis at 6, 12, 24, 36, and 48 h after the injection of CCl(4).

Effects of cysteine on the pharmacokinetics of itraconazole in rats with protein-calorie malnutrition.

The effects of cysteine on the pharmacokinetics of itraconazole were investigated after intravenous, 20 mg/kg, and oral, 50 mg/kg, administration of the drug to control rats (fed for 4 weeks on 23% casein diet) and rats with PCM (protein-calorie malnutrition, fed for 4 weeks on 5% casein diet) and PCMC (PCM with oral cysteine supplementation, 250 mg/kg, twice daily during the fourth week). After intravenous administration of itraconazole to rats with PCM, the area under the plasma concentration-time curve from time zero to time infinity (AUC) of itraconazole was significantly greater (3580 compared with 2670 and 2980 microg min/ml) than those in control rats and rats with PCMC (the values between control rats and rats with PCMC were not significantly different). The above data suggested that metabolism of itraconazole decreased significantly in rats with PCM due to suppression of hepatic microsomal cytochrome p450 (CYP) 3A23 in the rats.

Enhanced oral bioavailability of paclitaxel by coadministration of the P-glycoprotein inhibitor KR30031.

Purpose: In an attempt to improve the oral bioavailability of paclitaxel, a novel P-glycoprotein inhibitor, KR30031, which is verapamil analog with fewer cardiovascular effects, was coadministered with paclitaxel, and to elucidate other possible causes of the low oral bioavailability of paclitaxel, an inhibitor of hepatic metabolism, ketoconazole, was also coadministered with paclitaxel.

Methods: In vivo oral absorption was tested in rats, and an in vitro study was also performed with a Caco-2 cell monolayer to identify the extent of P-glycoprotein inhibition.

Results: After coadministration of paclitaxel with ketoconazole, KR-30031, or KR-30031 and ketoconazole, bioavailability was increased about 1.

Identification of estrogen-regulated genes in the mouse uterus using a delayed-implantation model.

Gonadal steroid hormones are known to modulate the implantation of the blastocyst, but how the controlling genetics are regulated remains largely unknown. Using a delayed-implantation model, we examined estrogen-regulated genes (ERGs) in the mouse uterus using the differential-display reverse transcription-polymerase chain reaction (DD RT-PCR). Pregnant mice were ovariectomized and injected daily with progesterone (P, 1 mg/mouse), followed by a single injection of estrogen (E, 200 ng/mouse); 24 or 48 hr later, total RNA was extracted from the uterus.

A case of primary esophageal B-cell lymphoma of MALT type, presenting as a submucosal tumor.

The primary esophageal lymphoma is extremely rare, and shows various morphologic characteristics. Only a single case of mucosa-associated lymphoid tissue (MALT) type lymphoma confined to the esophagus has been reported in the literature. A 61-yr-old man was referred to our hospital for evaluation of an esophageal submucosal tumor (SMT) that had been detected incidentally by endoscopy.

Effect of nitric oxide on the sinusoidal uptake of organic cations and anions by isolated hepatocytes.

The issue of whether or not the presence NOx (NO and oxidized metabolites) in the hepatocytes at pathological levels affects the functional activity of transport systems within the sinusoidal membrane was investigated. For this purpose, the effect of the pretreatment of isolated hepatocytes with sodium nitroprusside (SNP), a spontaneous NO donor, on the sinusoidal uptake of tributylmethylammonium (TBuMA) and triethylmethyl ammonium (TEMA), representative substrates of the organic cation transporter (OCT), and taurocholate, a representative substrate of the Na+/taurocholate cotransporting polypeptide (NTCP), was measured. The uptake of TBuMA and TEMA was not affected by the pretreatment, as demonstrated by the nearly identical kinetic parameters for the uptake (i.

Small intestinal transit does not adequately represent postoperative paralytic ileus in rats.

Small intestinal transit (SIT) has often been regarded as an index of pathophysiological state of postoperative ileus (PI) in rats. The reliability of SIT as an index of PI was examined in the present study. PI was induced via abdominal surgery (i.

Hepatobiliary excretion of tributylmethylamonium in rats with lipopolysaccharide-induced acute inflammation.

The alteration in the pharmacokinetic behaviors of organic cations (OCs) in rats during acute inflammation (Al) was investigated. Al was induced by an intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg) 24 hr prior to the start of pharmacokinetic studies. Tributylmethylammonium (TBuMA) was selected as a model OC since it is largely excreted into bile, and is neither metabolized nor binds to proteins in the body.

[A case of hepatocellular carcinoma with metastasis to gingival mucosa].

Hepatocellular carcinoma is one of the most common causes of death in Koreans. Most cases of hepatocellular carcinoma are beyond the stage of curative resection at the time of diagnosis due to extrahepatic metastasis as well as wide distribution of tumor in the liver. The lung is the most common site of extrahepatic metastasis but metastasis to gingiva is very rare in hepatocellular carcinoma.

Wire-guided intraductal US in the assessment of bile duct strictures with Mirizzi syndrome-like features at ERCP.

Background: Mirizzi syndrome refers to common hepatic duct obstruction caused by extrinsic compression that is usually from a stone impacted in the cystic duct. The utility of transpapillary intraductal US for assessment of biliary strictures with radiographic features of Mirizzi syndrome was studied retrospectively.

Methods: Intraductal US was performed in 16 patients with a common hepatic duct stricture caused by extrinsic compression and nonvisualization of the gallbladder by endoscopic retrograde cholangiography.

P-glycoprotein-mediated transport of berberine across Caco-2 cell monolayers.

The objective of this study was to investigate the mechanisms by which berberine is transported in the secretory and absorptive directions across Caco-2 cell monolayers. The basolateral-to-apical (B-A) flux was 30-fold greater than the apical-to-basolateral flux and temperature dependent (i.e.

Characterization of the transport of uracil across Caco-2 and LLC-PK1 cell monolayers.

Purpose: The purpose of this study was to characterize the transport of uracil, a pyrimidine nucleobase, in Caco-2 and LLC-PK, cells.

Methods: Caco-2 and LLC-PK1 cells were grown to confluency on a permeable polycarbonate membrane insert to permit transport and uptake experiments after the loading of uracil on either the apical or basolateral side.

Results: The vectorial transport of uracil in both directions was saturable with comparable Km and Vmax in Caco-2 cell monolayers, probably because of a Na+-independent transport system located on the basolateral membrane.

Preparation and evaluation of proliposomes containing salmon calcitonin.

Salmon calcitonin (sCT)-containing proliposomes were prepared by penetrating a methanol-chloroformic solution of sCT and phosphatidylcholine (PC) into microporous sorbitol particles, followed by vacuum evaporation of the solvent. As a result, sCT proliposomes with free-flowing flowability were obtained. On contact with water, the proliposomes were rapidly converted into a liposomal dispersion, in which a certain amount of sCT was entrapped by the liposomes.

Mechanism of the reduced elimination clearance of benzylpenicillin from cerebrospinal fluid in rats with intracisternal administration of lipopolysaccharide.

The mechanism responsible for the reduced clearance of benzylpenicillin (BPC) from the cerebrospinal fluid (CSF) was investigated in rats that received an intracisternal administration of lipopolysaccharide (LPS). BPC was intraventricularly injected and its elimination from the CSF studied. During the inflammation created by the LPS administration to the cisterna magna, the clearance of BPC and taurine from the CSF was significantly reduced but reverted to the control level when N-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, was intracisternally administered.

Effects of cysteine on the pharmacokinetics of intravenous chlorzoxazone in rats with protein-calorie malnutrition.

The effects of cysteine on the pharmacokinetics of chlorzoxazone (CZX) and one of its metabolites, 6-hydroxychlorzoxazone (OH-CZX), were investigated after intravenous administration of CZX, 25 mg/kg, to control rats (4-week fed on 23% casein diet) and rats with PCM (4-week fed on 5% casein diet) and PCMC (PCM with oral cysteine supplementation, 250 mg/kg, twice daily during the fourth week). In rats with PCM, the area under the plasma concentration-time curve from time zero to time infinity (AUC) of OH-CZX (436 compared with 972 microgmin/ml) and the percentages of intravenous dose of CZX excreted in 8-h urine as OH-CZX (20.2 compared with 38.

Simple liquid chromatography-electrospray ionization mass spectrometry method for the routine determination of salmon calcitonin in serum.

A simple liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method was developed for the quantification of salmon calcitonin (sCT) in serum. Serum samples from rats and dogs were deproteinized and freeze-dried. The residue was then reconstituted with 57% acetonitrile in water containing 0.

Use of detachable snares and elastic bands for endoscopic control of bleeding from large gastric varices.

Background: Bleeding from gastric varices larger than 2 cm in diameter represents a major limitation for endoscopic hemostasis.

Methods: Endoscopic ligation of gastric varices was performed with detachable snares and elastic bands in 41 patients who had recent bleeding from gastric varices larger than 2 cm in diameter. Gastric varices larger than 2 cm were ligated with detachable snares, and then adjacent small gastric varices were ligated with elastic bands.

Normal structure, variations, and anomalies of the pancreaticobiliary ducts of Koreans: a nationwide cooperative prospective study.

Background: This study evaluated the normal pancreaticobiliary ducts of Koreans and assessed the frequency and pattern of variations and anomalies of these structures.

Methods: A prospective, nationwide multicenter study was performed in which 10 university hospitals in Korea participated from March 1997 to June 1999. A total 10,243 patients undergoing ERCP were enrolled.

Biliary metal stent as a nidus for bile duct stone.

Several cases of recurrent stone formation caused by a surgical material as a nidus have been reported. Recently, we experienced one case in which a migrated metal stent might have been served as a nidus for common duct stone formation. The diagnosis was confirmed by ERCP, the stone was successfully removed with endoscopic therapy.

Effect of prokinetic agents, cisapride and metoclopramide, on the bioavailability in humans and intestinal permeability in rats of ranitidine, and intestinal charcoal transit in rats.

To investigate the effect of two prokinetic drugs, cisapride and metoclopramide, on the bioavailability of drugs, a marker drug, ranitidine, was administered to healthy volunteers following pre-treatments with or without the prokinetic agents. Cisapride or metoclopramide HCl (a respective dose of 10 mg) was administered orally 30 min prior to an oral administration of ranitidine (300 mg). Serum samples were collected for a 12 h period after the administration of ranitidine and the concentration of ranitidine was determined by an HPLC method.