Animals ; Chemical and Drug Induced Liver Injury ; drug therapy ; Liver ; drug effects ; pathology ; Mice ; Silymarin ; pharmacology ; Ursodeoxycholic Acid ; pharmacology

The purpose of this volunteer study was to investigate whether pretreatment with UDCA before the administration of 99mTc DISIDA affects the biliary excretion of the DISIDA, and whether it can shorten the total imaging time. Ten young, healthy volunteers (eight males, two females, mean age: 26.3 +/- 2.1 years) participated in the study. Hepatobiliary scintigraphies were performed twice per volunteer within three days, for the control and the UDCA-pretreated studies. In the control study, the gallbladder (GB) was observed first in four cases and the intestine was observed first in another four cases; in contrast, in the UDCA challenge study, the GB was observed first in eight cases. The quantitative results for the factors related to the GB differed significantly between the control and challenge studies. When the subjects were pretreated with UDCA, the time duration until visualization of the GB was shortened, and the maximum activity of the GB became more intense. In conclusion, UDCA pretreatment before hepatobiliary scintigraphy can shorten the total imaging time for evaluating functional obstructions of the cystic duct and increase the specificity of the process.
Adult ; Biliary Tract/*radionuclide imaging ; Female ; Humans ; Liver/*radionuclide imaging ; Male ; Radionuclide Imaging/*methods ; Radiopharmaceuticals/*pharmacokinetics ; Technetium Tc 99m Disofenin/*pharmacokinetics ; Ursodeoxycholic Acid/*pharmacology

OBJECTIVETo explore the influence of ursodeoxycholic acid on the therapeutic effects of low-calorie diet in steatohepatitis with obesity and hyperlipidemia.

METHODSThirty-five Sprague-Dawley rats fed with high-fat diet for 10 weeks were randomly allocated into 3 groups, and continued to experiment for 2 weeks. The animals in model group (n = 10) were still fed with high-fat diet; low-calorie diet group (n = 10) with common diet but only one third of the amount of normal demand; ursodeoxycholic acid group (n = 15) with low-calorie diet and ursodeoxycholic acid (15 mg/kg.d(-1)); and another 9 rats with common diet for 12 weeks as normal group.

RESULTSCompared with normal group, such indexes as body weight, liver weight, and the level of serum lipids and aminotransferase were all increased significantly in model group. Furthermore, all rats in model group developed steatohepatitis. On the other hand, such indexes as body weight and the degree of steatosis in rats of low-calorie diet group were decreased sharply compared with those in model group, but neither disorders of serum lipid nor the degree of hepatic inflammation and necrosis in low-calorie diet group were improved obviously. Disorders of serum lipid, aspartate aminotransferase, hepatic inflammation and necrosis in ursodeoxycholic acid group were ameliorated to some extent.

CONCLUSIONSUrsodeoxycholic acid might help to improve the therapeutic effects of low-calorie diet on steatohepatitis with obesity and hyperlipidemia.

Animals ; Diet ; Disease Models, Animal ; Food-Drug Interactions ; Hepatitis ; complications ; diet therapy ; Hyperlipidemias ; complications ; diet therapy ; Obesity ; complications ; diet therapy ; Rats ; Rats, Sprague-Dawley ; Ursodeoxycholic Acid ; pharmacology

To find novel antihepatitis drugs, a series of nitrate-oleanolic acid (OA) hybrids (10a, 10b, 11a-11e and 12a-12c) were designed and synthesized on the basis of previous studies using OA as lead compound, which is widely found in natural plants and liver-specific metabolism. In the present study, ten novel NO-releasing derivatives of OA were synthesized by connecting nitrate to the OA-3-OH through varying lengths of linkers containing antioxidants which were designed to increase the ability of these target compounds to scavenge free radicals. The structures of these objective compounds were determined by IR, MS, 1H NMR and elemental analysis. Their protective effects on anti-Fas mediated HepG2 cell apoptosis were in vitro evaluated by LDH assay. Compound 12a is the most potent inhibitor. Its effect on anti-Fas mediated HepG2 cell apoptosis and amount of NO-releasing in vitro are similar to those of positive control NCX-1000.
Antioxidants ; chemistry ; Apoptosis ; drug effects ; Hep G2 Cells ; Humans ; Nitrates ; chemical synthesis ; chemistry ; pharmacology ; Nitric Oxide ; metabolism ; Nitric Oxide Donors ; chemistry ; Oleanolic Acid ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship ; Ursodeoxycholic Acid ; analogs & derivatives ; pharmacology

Animals ; Biphenyl Compounds ; pharmacology ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Genetic Therapy ; Hepatocyte Growth Factor ; pharmacology ; Hepatocytes ; drug effects ; Humans ; Liver Cirrhosis ; pathology ; therapy ; Plants, Medicinal ; chemistry ; Ursodeoxycholic Acid ; pharmacology

Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.
Animals ; Mice ; Colitis, Ulcerative/drug therapy* ; Ursodeoxycholic Acid/adverse effects* ; Berberine/pharmacology* ; Interleukin-6 ; Tumor Necrosis Factor-alpha/pharmacology* ; Drugs, Chinese Herbal/pharmacology* ; Colon ; Nanoparticles ; Dextran Sulfate/adverse effects* ; Disease Models, Animal ; Colitis/chemically induced*

OBJECTIVETo provide evidence for three-level prevention of cholelithiasis by means of observing the effects of some choleretics on bile compositions drained from patients with pigment gallstone.

METHODSTwenty-seven patients suffering from primary pigment gallstones and having received treatment of choledochostomies plus T-tube or endoscopic nasal bile drainage (ENBD) were divided equally into three groups, and administered respectively with Lidanling (the LDL group), ursodesoxycholic acid (the UDA group) and combination of LDL and UDA (the LDL + UDA group) through oral intake (7 patients in each group). Besides, 6 post-operational patients got no treatment with any drug were allocated in the control group. Bile of all the patients was collected before treatment and on the 1, 3, 5, 7 th day after the treatment started to detect levels of total bile acid (TBA), glycocholic acid (GCA), taurocholic acid (TCA), glycocholic cheno-desoxycholic acid (GCDCA), total bilirubin (TBIL), uncombined bilirubin (UCB), concentration of calcium ion (Ca(2+)) as well as the bacterio-genetic and endogenous beta-glucuronidase activity for comparing.

RESULTSLevels of TBA, GCA, TCA and GCDCA got gradually increased in the UDA group and the LDL + UDA group after treatment (P < 0.05), while those in the LDL group remained unchanged, showing an insignificant difference as compared with those in the control group. In the LDL group and the LDL + UDA group, TBIL gradually increased while UCB gradually decreased in the course of treatment (P < 0.05). Moreover, levels of Ca(2+) and endogenous beta-glucuronidase activity got significantly lowered (P < 0.05).

CONCLUSIONCombined use of LDL and UDA could elevate levels of TBA, GCA, TCA, GCDCA, enhance the excretion of TBIL in patients with pigment gallstone after bile drainage, lower levels of UCB and Ca(2+) and the activity of endogenous beta-glucuronidase in the bile, so as to reduce the possibility of stone formation of bile, and therefore, it could be used to prevent the production of pigment gallstone, especially to prevent post-operative recurrence of stones.

Adult ; Bile ; chemistry ; Bile Acids and Salts ; analysis ; Bilirubin ; analysis ; Calcium ; analysis ; Cholagogues and Choleretics ; pharmacology ; Choledochostomy ; Cysteic Acid ; analogs & derivatives ; pharmacology ; Drainage ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gallstones ; metabolism ; Glucuronidase ; analysis ; Glycocholic Acid ; analysis ; Humans ; Male ; Middle Aged ; Taurocholic Acid ; analysis ; Ursodeoxycholic Acid ; analogs & derivatives ; pharmacology

To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) with oral solubilized formula in amyotrophic lateral sclerosis (ALS) patients, patients with probable or definite ALS were randomized to receive oral solubilized UDCA (3.5 g/140 mL/day) or placebo for 3 months after a run-in period of 1 month and switched to receive the other treatment for 3 months after a wash-out period of 1 month. The primary outcome was the rate of progression, assessed by the Appel ALS rating scale (AALSRS), and the secondary outcomes were the revised ALS functional rating scale (ALSFRS-R) and forced vital capacity (FVC). Fifty-three patients completed either the first or second period of study with only 16 of 63 enrolled patients given both treatments sequentially. The slope of AALSRS was 1.17 points/month lower while the patients were treated with UDCA than with placebo (95% CI for difference 0.08-2.26, P = 0.037), whereas the slopes of ALSFRS-R and FVC did not show significant differences between treatments. Gastrointestinal adverse events were more common with UDCA (P < 0.05). Oral solubilized UDCA seems to be tolerable in ALS patients, but we could not make firm conclusion regarding its efficacy, particularly due to the high attrition rate in this cross-over trial.
Administration, Oral ; Amyotrophic Lateral Sclerosis/*drug therapy ; Cholagogues and Choleretics/pharmacology/therapeutic use ; Cross-Over Studies ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Placebo Effect ; Severity of Illness Index ; Ursodeoxycholic Acid/pharmacology/*therapeutic use ; Vital Capacity/drug effects

Animals ; Apoptosis ; drug effects ; Azo Compounds ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Drug Delivery Systems ; Humans ; Liver ; metabolism ; Liver Neoplasms ; pathology ; Nitrates ; chemical synthesis ; pharmacology ; Nitric Oxide Donors ; chemical synthesis ; pharmacology ; Oleanolic Acid ; analogs & derivatives ; chemical synthesis ; pharmacology ; Piperazines ; chemical synthesis ; pharmacology ; Ursodeoxycholic Acid ; analogs & derivatives ; chemical synthesis ; pharmacology

BACKGROUND/AIMS: We aimed to explore the risk factors contributing to the recurrence of common bile duct (CBD) stones after successful endoscopic stone clearance, focused on the anatomical factors of CBD and presence or absence of ursodeoxycholic acid (UDCA)/Rowachol(R) medication. METHODS: One hundred fourteen patients who underwent CBD stone(s) extraction by endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy at our institution from August 2004 to January 2007 were included. Univariate and multivariate analyses for the risk factors including the distal CBD angle, length of the distal CBD arm and medication such as ursodeoxycholic acid (UDCA) and/or Rowachol(R) for recurrent CBD stone(s) were performed. RESULTS: The recurrence of CBD stone(s) was found in 22 (19.3%) patients. On univariate analysis, presence of pneumobilia, presence of type 1 or type 2 periampullary diverticulum, mechanical lithotripsy and multiple sessions of ERCP were significant contributors for the recurrence of CBD stone(s). On multivariate analysis, the presence of type 1 periampullary diverticulum (OR 7.90, 95% CI: 1.56-40.16) and multiple sessions of ERCP (OR 7.56, 95% CI: 2.21-25.87) were significant contributors. Acute distal CBD angulation (< or =135degrees), shorter distal CBD arm (< or =36 mm), technical difficulty of CBD stone(s) clearance, and the prescription of UDCA and/or Rowachol(R) were not significantly associated with the recurrence of CBD stone(s). CONCLUSIONS: The recurrence of CBD stone(s) was more commonly found in the patients group with type 1 periampullary diverticulum and multiple sessions of ERCP. Therefore, patients with these risk factors should be on regular follow up.
Aged ; Cholangiopancreatography, Endoscopic Retrograde ; *Common Bile Duct/radiography ; Data Interpretation, Statistical ; Female ; Gallstones/prevention & control/radiography/*surgery ; Humans ; Male ; Middle Aged ; Prospective Studies ; Recurrence ; Risk Factors ; *Sphincterotomy, Endoscopic ; Treatment Outcome ; Ursodeoxycholic Acid/pharmacology