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https://www.readbyqxmd.com/read/28543991/sensitivity-and-specificity-of-plasma-alt-alp-and-bile-acids-for-hepatitis-in-labrador-retrievers
#1
K Dirksen, I A Burgener, J Rothuizen, T S G A M van den Ingh, L C Penning, B Spee, H Fieten
BACKGROUND: Biochemical indicators for diagnosing liver disease are plasma alanine aminotransferase activity (ALT), alkaline phosphatase activity (ALP), and bile acid concentration (BA). OBJECTIVES: To determine the sensitivity and specificity of ALT, ALP, and BA for detecting primary hepatitis (PH) in clinically healthy Labrador retrievers and investigate whether ALT and ALP can discriminate between dogs with PH and nonspecific reactive hepatitis (RH). ANIMALS: 191 clinically healthy and 51 clinically ill Labrador retrievers with hepatic histopathology...
May 23, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28543964/linking-long-non-coding-rna-to-control-bile-acid-signaling-and-cholestatic-liver-fibrosis
#2
EDITORIAL
John Y L Chiang
No abstract text is available yet for this article.
May 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28543567/tgr5-contributes-to-hepatic-cystogenesis-in-rodents-with-polycystic-liver-diseases-via-camp-g%C3%AE-s-signaling
#3
Tatyana V Masyuk, Anatoliy I Masyuk, Maria Lorenzo Pisarello, Brynn N Howard, Bing Q Huang, Pui-Yuen Lee, Xavier Fung, Eduard Sergienko, Robert J Ardesky, Thomas Dy Chung, Anthony B Pinkerton, Nicholas F LaRusso
Hepatic cystogenesis in Polycystic Liver Disease (PLD) is associated with increased levels of cAMP in cholangiocytes lining liver cysts. TGR5, a G protein-coupled bile acid receptor, is linked to cAMP and expressed in cholangiocytes. Therefore, we hypothesized that TGR5 might contribute to disease progression. We examined expression of TGR5 and Gα proteins in cultured cholangiocytes and in livers of animal models and humans with PLD. In vitro, we assessed cholangiocyte proliferation, cAMP levels, and cyst growth in response to: (i) TGR5 agonists [taurolithocholic acid (TLCA), oleanolic acid (OA) and two synthetic compounds]; (ii) a novel TGR5 antagonist (SBI-115); and (iii) a combination of SBI-115 and pasireotide, a somatostatin receptor (SSTR) analog...
May 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28543298/synthesis-and-preclinical-pharmacokinetic-study-of-dha-10-a-novel-potential-antifungal-pogostone-analogue
#4
Ming Liu, Yanfen Zhou, Jianwei Zhu, Bo Ma, Zheng Fang, Qi Zhang
OBJECTIVES: The emergence of fungal disease calls for the urgency of development of novel drug. In this study, we developed a novel pogostone analogue, DHA-10 and investigated its preclinical pharmacokinetics, tissue distribution, excretion and protein binding rate in rats. METHODS: DHA-10 was synthesized with dehydroacetic acid (DHA) as the starting material and the structure confirmed by NMR and HRMS. The LC-MS/MS was applied to quantitative analysis of DHA-10 concentrations in the biological samples...
May 23, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28543042/the-ntcp-inhibitor-myrcludex-b-effects-on-bile-acid-disposition-and-tenofovir-pharmacokinetics
#5
Antje Blank, Annette Eidam, Mathias Haag, Nicolas Hohmann, Jürgen Burhenne, Matthias Schwab, Stan F J van de Graaf, Markus R Meyer, Hans H Maurer, Katrin Meier, Johanna Weiss, Thomas Bruckner, Alexander Alexandrov, Stephan Urban, Gerd Mikus, Walter E Haefeli
Myrcludex B acts as a hepatitis B and D virus entry inhibitor blocking the sodium taurocholate co-transporting polypeptide (SLC10A1). We investigated effects of myrcludex B on plasma bile acid disposition, tenofovir pharmacokinetics, and perpetrator characteristics on cytochrome P450 (CYP) 3A. Twelve healthy volunteers received 300 mg tenofovir disoproxil fumarate orally and 10 mg subcutaneous myrcludex B. Myrcludex B increased total plasma bile acid exposure 18.2-fold without signs of cholestasis. The rise in conjugated bile acids was up to 123-fold (taurocholic acid)...
May 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28542544/development-and-characterization-of-an-experimental-model-of-diet-induced-metabolic-syndrome-in-rabbit
#6
Oscar Julián Arias-Mutis, Vannina G Marrachelli, Amparo Ruiz-Saurí, Antonio Alberola, Jose Manuel Morales, Luis Such-Miquel, Daniel Monleon, Francisco J Chorro, Luis Such, Manuel Zarzoso
Metabolic syndrome (MetS) has become one of the main concerns for public health because of its link to cardiovascular disease. Murine models have been used to study the effect of MetS on the cardiovascular system, but they have limitations for studying cardiac electrophysiology. In contrast, the rabbit cardiac electrophysiology is similar to human, but a detailed characterization of the different components of MetS in this animal is still needed. Our objective was to develop and characterize a diet-induced experimental model of MetS that allows the study of cardiovascular remodeling and arrhythmogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28540169/establishment-of-a-new-acute-on-chronic-liver-failure-model
#7
Fangfang Li, Luyang Miao, Hua Sun, Yuyang Zhang, Xiuqi Bao, Dan Zhang
To establish an animal model of acute-on-chronic liver failure (ACLF) that would replicate the pathological process of ACLF in humans, rats were administered porcine serum (PS) for 11 weeks. Liver fibrosis was determined by pathological and biochemical assessments. The animals then were injected with d-galactosamine (d-gal) and lipopolysaccharide (LPS). The survival times of animals with cirrhosis and ACLF were determined over 48 h. Other animals were killed at 0, 4, 8 and 12 h after administration of d-gal/LPS...
May 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28539583/transient-receptor-potential-canonical-5-channels-plays-an-essential-role-in-hepatic-dyslipidemia-associated-with-cholestasis
#8
Khadija M Alawi, David Tandio, Jin Xu, Pratish Thakore, Georgia Papacleovoulou, Elizabeth S Fernandes, Cristina Legido-Quigley, Catherine Williamson, Susan D Brain
Transient receptor potential canonical 5 (TRPC5), a calcium-permeable, non-selective cation channel is expressed in the periphery, but there is limited knowledge of its regulatory roles in vivo. Endogenous modulators of TRPC5 include a range of phospholipids that have an established role in liver disease, including lysophosphatidylcholine (LPC). Cholestasis is characterized by impairment of excretion of bile acids, leading to elevation of hepatic bile acids. We investigated the contribution of TRPC5 in a murine model of cholestasis...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539269/ursodeoxycholic-acid-attenuates-experimental-autoimmune-arthritis-by-targeting-th17-and-inducing-pampk-and-transcriptional-corepressor-smile
#9
Eun Jung Lee, Jeong-Eun Kwon, Min-Jung Park, KyungAh Jung, Da-Som Kim, Eun-Kyung Kim, Seung Hoon Lee, Jong Young Choi, Sung-Hwan Park, Mi-La Cho
BACKGROUND: Ursodeoxycholic acid (UDCA), also known ursodiol, is a secondary bile acid. It has been known that UDCA has prominent effects on liver, however, there is little known about its influence on autoimmune disease. Here, the benefit of UDCA on arthritis rheumatoid (RA) in vivo was tested. METHODS: RA mouse were induced using collagen II (CIA, collagen induced arthritis) where the disease severity or UDCA-related signaling pathway such as AMP-activated protein kinase (AMPK) or small heterodimer partner interacting leucine zipper protein (SMILE) was evaluated by westerblot and immunohistochemical staining...
May 21, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28537673/comprehensive-analysis-of-microrna-mrna-signature-in-colon-adenocarcinoma
#10
J-Y Wang, C-L Wang, X-M Wang, F-J Liu
OBJECTIVE: The goal of our study was to identify the regulatory mechanisms of gene expression mediated by miRNAs and DNA methylation in colon adenocarcinoma (COAD). MATERIALS AND METHODS:   The miRNAs and mRNAs expression and DNA methylation data of COAD and adjacent normal tissues were obtained from The Cancer Genome Atlas (TCGA) database. Based on the differentially expressed miRNAs and mRNAs, miRNA-mRNA pairs were obtained by correlation analysis and prediction algorithms...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28537659/metformin-improves-the-glucose-and-lipid-metabolism-via-influencing-the-level-of-serum-total-bile-acids-in-rats-with-streptozotocin-induced-type-2-diabetes-mellitus
#11
X-M Meng, X-X Ma, Y-L Tian, Q Jiang, L-L Wang, R Shi, L Ding, S-G Pang
OBJECTIVE: To study the effects of metformin on streptozotocin-induced type 2 diabetes mellitus (T2DM) in rats. MATERIALS AND METHODS: Wistar male rats were divided into two groups: standard diet (SD, n = 20) group and high-fat diet (HFD, n = 80) group. Twenty rats in HFD group were randomly treated with metformin (EI group). After 6 weeks, among rats in HFD group, 20 rats were intraperitoneally injected with citrate buffered saline (IR group), 20 rats treated with metformin per day for 4 weeks (LI group), and 20 rats were given nothing (DM group)...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28536529/activation-of-sirt1-fxr-signaling-pathway-attenuates-triptolide-induced-hepatotoxicity-in-rats
#12
Jing Yang, Lixin Sun, Lu Wang, Hozeifa M Hassan, Xuan Wang, Phillip B Hylemon, Tao Wang, Huiping Zhou, Luyong Zhang, Zhenzhou Jiang
Triptolide (TP), a diterpenoid isolated from Tripterygium wilfordii Hook F, has an excellent pharmacological profile of immunosuppression and anti-tumor activities, but its clinical applications are severely restricted due to its severe and cumulative toxicities. The farnesoid X receptor (FXR) is the master bile acid nuclear receptor and plays an important role in maintaining hepatic metabolism homeostasis. Hepatic Sirtuin (Sirt1) is a key regulator of the FXR signaling pathway and hepatic metabolism homeostasis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28534273/tauroursodeoxycholic-acid-enhances-mitochondrial-biogenesis-neural-stem-cell-pool-and-early-neurogenesis-in-adult-rats
#13
Rita Soares, Filipa F Ribeiro, Sara Xapelli, Tânia Genebra, Maria F Ribeiro, Ana M Sebastião, Cecília M P Rodrigues, Susana Solá
Although neurogenesis occurs in restricted regions of the adult mammalian brain, neural stem cells (NSCs) produce very few neurons during ageing or after injury. We have recently discovered that the endogenous bile acid tauroursodeoxycholic acid (TUDCA), a strong inhibitor of mitochondrial apoptosis and a neuroprotective in animal models of neurodegenerative disorders, also enhances NSC proliferation, self-renewal, and neuronal conversion by improving mitochondrial integrity and function of NSCs. In the present study, we explore the effect of TUDCA on regulation of NSC fate in neurogenic niches, the subventricular zone (SVZ) of the lateral ventricles and the hippocampal dentate gyrus (DG), using rat postnatal neurospheres and adult rats exposed to the bile acid...
May 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28533986/atorvastatin-alters-the-expression-of-genes-related-to-bile-acid-metabolism-and-circadian-clock-in-livers-of-mice
#14
Wen-Kai Li, Huan Li, Yuan-Fu Lu, Ying-Ying Li, Zidong Donna Fu, Jie Liu
AIM: Atorvastatin is a HMG-CoA reductase inhibitor used for hyperlipidemia. Atorvastatin is generally safe but may induce cholestasis. The present study aimed to examine the effects of atorvastatin on hepatic gene expression related to bile acid metabolism and homeostasis, as well as the expression of circadian clock genes in livers of mice. METHODS: Adult male mice were given atorvastatin (10, 30, and 100 mg/kg, po) daily for 30 days, and blood biochemistry, histopathology, and gene expression were examined...
2017: PeerJ
https://www.readbyqxmd.com/read/28533304/modulation-of-the-gut-microbiota-impacts-non-alcoholic-fatty-liver-disease-a-potential-role-for-bile-acids
#15
Aafke Wf Janssen, Tom Houben, Saeed Katiraei, Wieneke Dijk, Lily Boutens, Nieke van der Bolt, Zeneng Wang, J Mark Brown, Stanley L Hazen, Stéphane Mandard, Ronit Shiri-Sverdlov, Folkert Kuipers, Ko Willems van Dijk, Jacques Vervoort, Rinke Stienstra, Guido Jej Hooiveld, Sander Kersten
Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide, yet the pathogenesis of NAFLD is only partially understood. Here, we investigated the role of the gut bacteria in NAFLD by stimulating the gut bacteria via feeding mice the fermentable dietary fiber guar gum and suppressing the gut bacteria via chronic oral administration of antibiotics. Guar gum feeding profoundly altered the gut microbiota composition, in parallel with reduced diet-induced obesity and improved glucose tolerance...
May 22, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28530150/the-roles-of-bile-acids-and-applications-of-microencapsulation-technology-in-treating-type-1-diabetes-mellitus
#16
Louise Woodhams, Hani Al-Salami
Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the loss of glycemic control. Recent studies have shown significant inflammation and disturbed bile acid homeostasis, associated with T1DM. Bile acids are endogenously produced as a result of cholesterol catabolism in the liver and solely metabolized by gut microflora. This review investigates their potential oral delivery in T1DM using targeted delivery and encapsulation technologies. A sensitive and selective search was carried out using different search engines and databases...
June 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/28529147/norursodeoxycholic-acid-improves-cholestasis-in-primary-sclerosing-cholangitis
#17
Peter Fickert, Gideon M Hirschfield, Gerald Denk, Hanns-Ulrich Marschall, Istvan Altorjay, Martti Färkkilä, Christoph Schramm, Ulrich Spengler, Roger Chapman, Annika Bergquist, Erik Schrumpf, Frederik Nevens, Palak Trivedi, Florian P Reiter, Istvan Tornai, Emina Halilbasic, Roland Greinwald, Markus Pröls, Michael P Manns, Michael Trauner
Primary sclerosing cholangitis (PSC) represents a devastating bile duct disease lacking effective medical therapy. 24-norursodeoxycholic acid (norUDCA) is a side chain-shortened C23 homologue of UDCA and has shown potent anti-cholestatic, anti-inflammatory and anti-fibrotic properties in a preclinical PSC mouse model. AIM: To evaluate the safety and efficacy of 3 doses of oral norUDCA (500mg/d, 1000mg/d or 1500 mg/d) compared with placebo in PSC in a RCT including 38centers from 12European countries...
May 18, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28529062/quantitative-targeted-bile-acid-profiling-as-new-markers-for-dili-in-a-model-of-methapyrilene-induced-liver-injury-in-rats
#18
Markus Slopianka, Anne Herrmann, Mira Pavkovic, Heidrun Ellinger-Ziegelbauer, Rainer Ernst, Angela Mally, Matthias Keck, Bjoern Riefke
Recently, bile acids (BAs) were reported as promising markers for drug-induced liver injury (DILI). BAs have been suggested to correlate with hepatocellular and hepatobiliary damage; however a clear connection of BA patterns with different types of DILI remains to be established. To investigate if BAs can improve the assessment of liver injury, 20 specific BAs were quantitatively profiled via LC-MS/MS in plasma and liver tissue in a model of methapyrilene-induced liver injury in rats. Methapyrilene, a known hepatotoxin was dosed daily over 14-days at doses of 30 and 80mg/kg, followed by a recovery phase of 10days...
May 19, 2017: Toxicology
https://www.readbyqxmd.com/read/28529037/diabetes-development-increased-concentrations-of-the-conjugated-bile-acid-taurocholic-acid-in-serum-while-treatment-with-microencapsulated-taurocholic-acid-exerted-no-hypoglycaemic-effects
#19
Sangeetha Mathavan, Momir Mikov, Svetlana Golocorbin-Kon, Hani Al-Salami
CONTEXT: The bile acid taurocholic acid (TCA) is endogenously produced, and has shown formulation-stabilising effects when incorporated into microcapsules containing potential antidiabetic drugs. This study aimed to develop and characterise TCA-microcapsules, and test their antidiabetic effects, in an animal model of Type 1 diabetes (T1D). METHODS: Using the polymer sodium alginate (SA), SA-microcapsules (control) and TCA-microcapsules (test) were prepared, and assessed for morphology, surface composition, chemical and thermal stability, swelling, buoyancy, mechanical, release and rheological properties...
May 18, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28527325/dyslipidemia-management-update
#20
REVIEW
Yingzi Chang, Jacques Robidoux
Association of hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD) is well established. Reducing low-density lipoprotein-cholesterol (LDL-C) and raising high-density lipoprotein-cholesterol (HDL-C) have been the therapeutic targets to reduce the risk of ASCVD. Cholesterol-lowering medications have been used to provide both primary and secondary prevention of ASCVD for many years by reducing the absorption and reabsorption, promoting excretion, or decreasing the synthesis of cholesterol. Within the past five years, several new classes of cholesterol-lowering drugs have been tested and approved for patients with hypercholesterolemia that are not well controlled by conventional therapy (ezetimibe, bile-acid sequestrants, and statins)...
May 17, 2017: Current Opinion in Pharmacology
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