Chemical and Drug Induced Liver Injury ; Humans ; Ursodeoxycholic Acid ; adverse effects

Cholestasis ; etiology ; physiopathology ; therapy ; Female ; Humans ; Liver Diseases ; drug therapy ; etiology ; physiopathology ; Male ; Neonatology ; Parenteral Nutrition, Total ; adverse effects ; S-Adenosylmethionine ; therapeutic use ; Ursodeoxycholic Acid ; therapeutic use

Glutathione is a tripeptide comprised by L-glutamate, L-cysteine, and glycine, that serves antioxygenation and deintoxication functions within the cell. Recent study has found that glutathione is the main driving force for bile salt-independent bile flow, impaired biliary excretion of glutathione can lead to cholestasis. This review focuses on hepatobiliary transport of glutathione and its role in cholestasis. Based on the evidence of choleretic effect of glutathione, enhancement of biliary excretion of glutathione may be a good strategy for prevention and treatment of cholestasis.
Animals ; Biological Transport ; Cholestasis ; chemically induced ; metabolism ; prevention & control ; Estrogens ; adverse effects ; Glutathione ; metabolism ; Humans ; Jaundice, Chronic Idiopathic ; genetics ; Liver ; metabolism ; Multidrug Resistance-Associated Proteins ; genetics ; metabolism ; Mutation ; Phalloidine ; adverse effects ; Ursodeoxycholic Acid ; therapeutic use

OBJECTIVETo conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) that have assessed the effect and safety of ursodeoxycholic acid (UDCA), S-adenosylmethionine (SAMe) and UDCA-SAMe combination therapies for intrahepatic cholestasis of pregnancy (ICP).

METHODSUsing searching protocols and assessment methods recommended by the Cochrane Collaboration to reduce bias in systematic reviews, the databases of Medline, EMBASE, Cochrane Central Register of Controlled Trials (CCRT), China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature (CBM) and Wanfang China Online Journals were searched to identify relevant RCTs published from database inception to December 2011.

RESULTSTen RCTs (of 727 pregnant women) were included in the study and represented a low risk for bias. Compared to the patients who received UDCA monotherapy, those who received UDCA-SAMe combination therapy had significantly lower rates of Cesarean section (odds ratio (OR) =0.45, 95% confidence interval (CI):0.24-0.86), preterm birth (OR=0.36, 95% CI:0.20-0.63), and fetal asphyxia (OR=0.27, 95% CI:0.13-0.56) (all P less than 0.05); however, the UDCA-SAMe therapy did not provide better rates of amniotic fluid pollution (OR=0.38, 95% CI:0.14-1.01) or better new bom weight (mean difference (MD) =397.36, 95% CI:-96.17-890.89). Compared to the patients who received SAMe monotherapy, those who received UDCA-SAMe combination therapy had significantly lower rates of preterm birth (OR=0.39, 95% CI:0.21-0.73), fetal asphyxia (OR=0.23, 95% CI:0.07-0.75), and amniotic fluid pollution (OR=0.41, 95% CI:0.20-0.85) (all, P less than 0.05); however, the UDCA-SAMe therapy did not provide better rates of Cesarean section (OR =0.62, 95% CI:0.27-1.44) or better new bom weight (MD =445.95, 95% CI:-143.51-1035.42). Comparison of the two monotherapies (UCDA vs.SAMe) showed no statistical differences in rates of Cesarean section (OR=0.91, 95% CI:0.47-1.78), preterm birth (OR =0.79, 95% CI:0.49-1.38), fetal asphyxia (OR=0.90, 95% CI:0.38-2.12), and amniotic fluid pollution (OR=1.14, 95% CI:0.61-2.13), as well as of new born weight (MD =-62.86, 95% CI:-157.81-32.09). Six studies reported no side effects.None of the included studies reported use of allocation concealment or blinding.

CONCLUSIONUDCA-SAMe combination therapy is better than either UDCA or SAMe monotherapy for improving the outcome of ICP without adverse effects. Large-scale trials with adequate sample sizes and higher quality study design are needed to further confirm the efficiency and safety of UDCA and SAMe for treating ICP.

Cholestasis, Intrahepatic ; drug therapy ; Drug Therapy, Combination ; Female ; Humans ; Pregnancy ; Pregnancy Complications ; drug therapy ; Pregnancy Outcome ; Randomized Controlled Trials as Topic ; S-Adenosylmethionine ; administration & dosage ; adverse effects ; therapeutic use ; Ursodeoxycholic Acid ; administration & dosage ; adverse effects ; therapeutic use

BACKGROUNDFatigue is a common symptom both in diseases status and in healthy subjects. Various supplements and nutraceuticals for relieving of fatigue have been used. However, there are a few studies to evaluate the efficacy and the safety of the drug for fatigue alleviation, we conducted using URSA Complex to evaluate the efficacy on physical fatigue via score changes in the checklist individual strength (CIS).

METHODSThe study was designed as a multicenter, randomized, double-blind, placebo-controlled trial, with subjects randomized to one of the two arms, receiving either placebo or URSA Complex administered as identical capsules. The primary efficacy endpoints of this clinical trials are the ratio of improving CIS scores < 76 points in patients at the end (4 weeks). Secondary efficacy variables are as follows one is an improvement of fatigue and the other is an improvement of the liver enzyme.

RESULTSThe fatigue recovery rate in who had improved CIS scores of < 76 points were 70.0%, 50.9% in the therapy group and placebo group, respectively (P = 0.019). The fatigue recovery rate in CIS score was higher in URSA Complex therapy group than placebo group. The difference between therapy group and placebo group was statistically significant at 4 weeks later, but not 2 weeks.

CONCLUSIONSOur results provided that the URSA Complex was effective in alleviating physical fatigue. The adverse event frequency in the therapy groups was similar to that in the placebo group.

Adult ; Double-Blind Method ; Fatigue ; drug therapy ; Humans ; Inositol ; therapeutic use ; Middle Aged ; Panax ; chemistry ; Plant Extracts ; chemistry ; Taurine ; adverse effects ; therapeutic use ; Thiamine ; therapeutic use ; Treatment Outcome ; Ursodeoxycholic Acid ; adverse effects ; therapeutic use

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*

Nonalcoholic steatohepatitis (NASH) can progress into liver cirrhosis; however, no definite treatment is available. Omega-3 polyunsaturated fatty acid (omega-3) has been reported to alleviate experimental NASH, although its beneficial effect was not evident when tested clinically. Thus, this study aimed to investigate the additive effect of omega-3 and ursodeoxycholic acid (UDCA) on diet-induced NASH in mice. C57BL/6 mice were given a high-fat diet (HFD) for 24 weeks, at which point the mice were divided into three groups and fed HFD alone, HFD with omega-3 or HFD with omega-3 in combination with UDCA for another 24 weeks. Feeding mice an HFD and administering omega-3 improved histologically assessed liver fibrosis, and UDCA in combination with omega-3 further attenuated this disease. The assessment of collagen alpha1(I) expression agreed with the histological evaluation. Omega-3 in combination with UDCA resulted in a significant attenuation of inflammation whereas administering omega-3 alone failed to improve histologically assessed liver inflammation. Quantitative analysis of tumor necrosis factor alpha showed an additive effect of omega-3 and UDCA on liver inflammation. HFD-induced hepatic triglyceride accumulation was attenuated by omega-3 and adding UDCA accentuated this effect. In accordance with this result, the expression of sterol regulatory binding protein-1c decreased after omega-3 administration and adding UDCA further diminished SREBP-1c expression. The expression of inducible nitric oxide synthase (iNOS), which may reflect oxidative stress-induced tissue damage, was suppressed by omega-3 administration and adding UDCA further attenuated iNOS expression. These results demonstrated an additive effect of omega-3 and UDCA for alleviating fibrosis, inflammation and steatosis in diet-induced NASH.
Animals ; Cholagogues and Choleretics/pharmacology/*therapeutic use ; Diet, High-Fat/adverse effects ; Drug Synergism ; Fatty Acids, Omega-3/pharmacology/*therapeutic use ; Fibrosis/drug therapy/etiology/immunology/pathology ; Inflammation/drug therapy/etiology/immunology/pathology ; Liver/*drug effects/immunology/pathology ; Male ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/*drug therapy/etiology/immunology/pathology ; Ursodeoxycholic Acid/pharmacology/*therapeutic use

Biliary cast describes the presence of casts within the biliary tree. It is resultant sequel of cholangitis and hepatocyte damage secondary to bile stasis and bile duct injury. Biliary cast syndrome was first reported in patient undergone liver transplantation. The pathogenesis of biliary cast is not clearly identified, but proposed etiologic factors include post-transplant bile duct damage, ischemia, biliary infection, or post-operative biliary drainage tube. Although biliary casts are uncommon, most of biliary cast syndrome are reported in the liver transplant or hepatic surgery patients. A few reports have been published about non-transplant or non-liver surgery biliary cast. We report two cases of biliary cast syndrome in non-liver surgery patients.
Acute Disease ; Ascariasis/diagnosis ; Bile Duct Diseases/*diagnosis/ultrasonography ; Bile Ducts/ultrasonography ; Cholagogues and Choleretics/therapeutic use ; Cholangiopancreatography, Endoscopic Retrograde/adverse effects ; Female ; Gallstones/diagnosis ; Humans ; Liver Cirrhosis, Biliary/diagnosis/drug therapy ; Male ; Middle Aged ; Pancreatitis/etiology ; Tomography, X-Ray Computed ; Ursodeoxycholic Acid/therapeutic use