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Drug-induced liver disease

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https://www.readbyqxmd.com/read/28344991/antibody-directed-glucocorticoid-targeting-to-cd163-in-m2-type-macrophages-attenuates-fructose-induced-liver-inflammatory-changes
#1
Pia Svendsen, Jonas H Graversen, Anders Etzerodt, Henrik Hager, Rasmus Røge, Henning Grønbæk, Erik I Christensen, Holger J Møller, Hendrik Vilstrup, Søren K Moestrup
Increased consumption of high-caloric carbohydrates contributes substantially to endemic non-alcoholic fatty liver disease in humans, covering a histological spectrum from fatty liver to steatohepatitis. Hypercaloric intake and lipogenetic effects of fructose and endotoxin-driven activation of liver macrophages are suggested to be essential to disease progression. In the present study, we show that a low dose of an anti-CD163-IgG-dexamethasone conjugate targeting the hemoglobin scavenger receptor CD163 in Kupffer cells and other M2-type macrophages has a profound effect on liver inflammatory changes in rats on a high-fructose diet...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28336942/selective-inhibitor-of-wnt-%C3%AE-catenin-cbp-signaling-ameliorates-hepatitis-c-virus-induced-liver-fibrosis-in-mouse-model
#2
Yuko Tokunaga, Yosuke Osawa, Takahiro Ohtsuki, Yukiko Hayashi, Kenzaburo Yamaji, Daisuke Yamane, Mitsuko Hara, Keisuke Munekata, Kyoko Tsukiyama-Kohara, Tsunekazu Hishima, Soichi Kojima, Kiminori Kimura, Michinori Kohara
Chronic hepatitis C virus (HCV) infection is one of the major causes of serious liver diseases, including liver cirrhosis. There are no anti-fibrotic drugs with efficacy against liver cirrhosis. Wnt/β-catenin signaling has been implicated in the pathogenesis of a variety of tissue fibrosis. In the present study, we investigated the effects of a β-catenin/CBP (cyclic AMP response element binding protein) inhibitor on liver fibrosis. The anti-fibrotic activity of PRI-724, a selective inhibitor of β-catenin/CBP, was assessed in HCV GT1b transgenic mice at 18 months after HCV genome expression...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28333601/simultaneous-occurrence-of-varicella-zoster-virus-induced-pancreatitis-and-hepatitis-in-a-renal-transplant-recipient-a-case-report-and-review-of-literature
#3
Puneet Chhabra, Priyadarshi Ranjan, Deepak K Bhasin
INTRODUCTION: Gastrointestinal complications are common after renal transplantation, including oral lesions, esophagitis, gastritis, diarrhea, and colon carcinoma. The differential diagnosis is difficult in this scenario because multiple factors such as drugs, infections, and preexisting gastrointestinal disease come into play. CASE PRESENTATION: We report a case of varicella zoster virus-induced pancreatitis and hepatitis in a renal transplant recipient. The patient underwent renal transplantation 3 years earlier and now presented with severe pain in the epigastrium radiating to his back and had raised serum lipase levels and skin lesions characteristic of varicella...
2017: Permanente Journal
https://www.readbyqxmd.com/read/28333073/effects-of-melatonin-on-liver-injuries-and-diseases
#4
REVIEW
Jiao-Jiao Zhang, Xiao Meng, Ya Li, Yue Zhou, Dong-Ping Xu, Sha Li, Hua-Bin Li
Liver injuries and diseases are serious health problems worldwide. Various factors, such as chemical pollutants, drugs, and alcohol, could induce liver injuries. Liver diseases involve a wide range of liver pathologies, including hepatic steatosis, fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocarcinoma. Despite all the studies performed up to now, therapy choices for liver injuries and diseases are very few. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries and diseases remains a priority...
March 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28332824/indole-substituted-benzothiazoles-and-benzoxazoles-as-selective-and-reversible-mao-b-inhibitors-for-treatment-of-parkinson-s-disease
#5
Min-Ho Nam, Moosung Park, Hyeri Park, Youngjae Kim, Seulki Yoon, Vikram Shahaji Sawant, Ji Won Choi, Jong-Hyun Park, Ki Duk Park, Sun-Joon Min, Changjoon Justin Lee, Hyunah Choo
To develop a novel, selective, and reversible MAO-B inhibitors for safer treatment of Parkinson's disease, benzothiazole and benzoxazole derivatives with indole moiety were designed and synthesized. Most of the synthesized compounds showed inhibitory activities against MAO-B and selectivity over MAO-A. The most active compound was Compound 5b, 6-fluoro-2-(1-methyl-1H-indol-5-yl)benzo[d]thiazole with an IC50 value of 29 nM with no apparent effect on MAO-A activity at 10 M. Based on the reversibility assay, Compound 5b turned out to be a fully reversible with over 95% of recovery of enzyme activity after washout of the compound...
March 23, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28331914/effects-and-mechanisms-of-a-new-multivitamin-on-chronic-metabolic-syndromes-and-aging
#6
Su-Xi Wu, Xuewei Jiang, Yu-Ying Liu, Lin-Feng Chen, Jun Tao
BACKGROUND: Increased occurrence of chronic syndromes has prompted researchers to investigate and develop drugs and methods for controlling chronic syndromes with a view to improve human health and reduce early aging. MATERIAL AND METHODS: Human trials: After the allotted multivitamin pills or placebo pills had been taken for a stipulated period of about 2 months, the volunteers filled out feedback forms on curative effects of the pills in line with the health examination reports...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28330614/a-predictive-3d-multi-scale-model-of-biliary-fluid-dynamics-in-the-liver-lobule
#7
Kirstin Meyer, Oleksandr Ostrenko, Georgios Bourantas, Hernan Morales-Navarrete, Natalie Porat-Shliom, Fabian Segovia-Miranda, Hidenori Nonaka, Ali Ghaemi, Jean-Marc Verbavatz, Lutz Brusch, Ivo Sbalzarini, Yannis Kalaidzidis, Roberto Weigert, Marino Zerial
Bile, the central metabolic product of the liver, is transported by the bile canaliculi network. The impairment of bile flow in cholestatic liver diseases has urged a demand for insights into its regulation. Here, we developed a predictive 3D multi-scale model that simulates fluid dynamic properties successively from the subcellular to the tissue level. The model integrates the structure of the bile canalicular network in the mouse liver lobule, as determined by high-resolution confocal and serial block-face scanning electron microscopy, with measurements of bile transport by intravital microscopy...
March 15, 2017: Cell Systems
https://www.readbyqxmd.com/read/28324010/separating-the-anti-inflammatory-and-diabetogenic-effects-of-glucocorticoids-through-lxr%C3%AE-antagonism
#8
Rucha Patel, Lilia Magomedova, Ricky Tsai, Stéphane Angers, Arturo Orellana, Carolyn L Cummins
Synthetic glucocorticoids (GCs) including dexamethasone (DEX) are powerful anti-inflammatory drugs. Long-term use of GCs, however, can result in metabolic side effects such as hyperglycemia, hepatosteatosis, and insulin resistance. The glucocorticoid receptor (GR) and liver X receptors (LXRα and LXRβ) regulate overlapping genes involved in gluconeogenesis and inflammation. We have previously shown that Lxrβ-/- mice are resistant to the diabetogenic effects of DEX, but still sensitive to its immunosuppressive actions...
January 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322783/elevation-of-liver-endoplasmic-reticulum-stress-in-a-modified-choline-deficient-l-amino-acid-defined-diet-fed-non-alcoholic-steatohepatitis-mouse-model
#9
Yo Muraki, Yukimasa Makita, Midori Yamasaki, Yuichiro Amano, Takanori Matsuo
Endoplasmic reticulum (ER) stress caused by accumulation of misfolded proteins is observed in several kinds of diseases. Since ER stress is reported to be involved in the progression of non-alcoholic steatohepatitis (NASH), highly sensitive and simple measurement methods are required for research into developing novel therapy for NASH. To investigate the involvement of ER stress in NASH pathogenesis in a mouse model, an assay for liver ER stress was developed using ER stress activated indicator-luciferase (ERAI-Luc) mice...
March 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28321390/metabonomics-research-progress-on-liver-diseases
#10
REVIEW
Mengqian Yu, Ying Zhu, Qingwei Cong, Chunyan Wu
Metabolomics as the new omics technique develops after genomics, transcriptomics, and proteomics and has rapid development at present. Liver diseases are worldwide public health problems. In China, chronic hepatitis B and its secondary diseases are the common liver diseases. They can be diagnosed by the combination of history, virology, liver function, and medical imaging. However, some patients seldom have relevant physical examination, so the diagnosis may be delayed. Many other liver diseases, such as drug-induced liver injury (DILI), alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), and autoimmune liver diseases, still do not have definite diagnostic markers; the diagnosis consists of history, medical imaging, and the relevant score...
2017: Canadian Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28320470/methimazole-associated-eosinophilic-pleural-effusion-a-case-report
#11
Pedro Gaspar-da-Costa, Filipa Duarte Silva, Júlia Henriques, Sónia do Vale, Sandra Braz, João Meneses Santos, Rui M M Victorino
BACKGROUND: Adverse reactions associated to anti-thyroid drugs include fever, rash, arthralgia, agranulocytosis and hepatitis that are thought to be hypersensitivity reactions. Five cases of pleural effusion associated to thionamides have also been reported, two with propylthiouracil and three with carbimazole. CASE PRESENTATION: We report here a case of a 75-year-old man admitted because of unilateral pleural effusion. The patient had a recent diagnosis of hyperthyroidism and 6 days after starting methimazole complained of pleuritic chest pain...
March 21, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28320320/antiviral-activity-of-pha767491-against-human-herpes-simplex-virus-in-vitro-and-in-vivo
#12
Jue Hou, Zili Zhang, Qiang Huang, Jun Yan, Xiaohu Zhang, Xiaoliang Yu, Guihua Tan, Chunfu Zheng, Feng Xu, Sudan He
BACKGROUND: Herpes simplex virus (HSV) is a common human pathogen that causes a variety of diseases, including oral-labial, genital lesions and life-threatening encephalitis. The antiviral nucleoside analogues such as acyclovir are currently used in anti-HSV therapies; however, clinical overuse of these drugs has led to the emergence of drug-resistant viral strains. Hence, there is an urgent need to develop new anti-HSV agents. METHODS: To identify novel anti-HSV-1 compounds, we screened the LOPAC small scale library of 1280 bioactive compounds to identify inhibitors of HSV-1-induced necroptosis...
March 20, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28319060/the-anti-diabetic-drug-exenatide-a-glucagon-like-peptide-1-receptor-agonist-counteracts-hepatocarcinogenesis-through-camp-pka-egfr-stat3-axis
#13
M Zhou, M T S Mok, H Sun, A W Chan, Y Huang, A S L Cheng, G Xu
Epidemiological studies have demonstrated a close association of type 2 diabetes and hepatocellular carcinoma (HCC). Exenatide (Ex-4), a potent diabetes drug targeting glucagon-like peptide-1 receptor (GLP-1R), is protective against non-alcoholic fatty liver disease (NAFLD). However, the Ex-4 function and GLP-1R status have yet been explored in HCC. Herein we investigated the effect of Ex-4 in diethylnitrosamine (DEN)-treated mice consuming control or high-fat high-carbohydrate diet. Administration of Ex-4 significantly improved obesity-induced hyperglycemia and hyperlipidemia and reduced HCC multiplicity in obese DEN-treated mice, in which suppressed proliferation and induced apoptosis were confined to tumor cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28315901/the-effect-of-sitagliptin-on-lipid-metabolism-of-fatty-liver-mice-and-related-mechanisms
#14
Bilin Xu, Tian Shen, Lin Chen, Juan Xia, Cuiping Zhang, Hongping Wang, Ming Yu, Tao Lei
BACKGROUND In clinics, patients with type 2 diabetes complicated with non-alcoholic fatty liver disease (NAFLD) have been shown to receive significant improvements in blood glucose levels, lipid levels, and liver function after sitagliptin treatment, although the mechanism of drug action remains poorly understood. This study investigated the possible mechanism of sitagliptin on lipid metabolism of NAFLD mice. MATERIAL AND METHODS Male C57/BL6 mice were induced for NAFLD via 16 weeks of a high-fat diet, and were treated with 15 mg/kg/day sitagliptin for 16 consecutive weeks...
March 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28304119/serum-markers-for-mitochondrial-dysfunction-and-cell-death-are-possible-predictive-indicators-for-drug-induced-liver-injury-by-direct-acting-antivirals
#15
Keisuke Kakisaka, Yuichi Yoshida, Yuji Suzuki, Takuro Sato, Hidekatsu Kuroda, Akio Miyasaka, Yasuhiro Takikawa
BACKGROUND & AIM: We prospectively screened patients treated with direct-acting antivirals (DAAs) in order to detect and analyze serum markers that are present prior to the development of drug-induced liver injury (DILI). METHODS: The levels of various serum markers among DILI, non-DILI, and control groups were compared. The DILI group consisted of 8 patients whose alanine aminotransferase (ALT) levels exceeded 32 IU/L during the DAA treatment. Eight patients without DILI were selected for the non-DILI group via a matched-group design based on age, gender, and disease severity...
March 17, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28292360/acute-on-chronic-liver-failure-causes-clinical-characteristics-and-predictors-of-mortality
#16
Abbas Ali Tasneem, Nasir Hassan Luck
OBJECTIVE: To determine the causes, characteristics and predictors of mortality in patients with acute-on-chronic liver failure (ACLF). STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, from July 2014 to June 2016. METHODOLOGY: All patients with acute-on-chronic liver disease (ACLD) with ages > 12 were included...
January 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28281441/miliary-tuberculosis
#17
Surendra K Sharma, Alladi Mohan
Miliary tuberculosis (TB) results from a massive lymphohematogenous dissemination of Mycobacterium tuberculosis bacilli and is characterized by tiny tubercles evident on gross pathology resembling millet seeds in size and appearance. The global HIV/AIDS pandemic and widespread use of immunosuppressive drugs and biologicals have altered the epidemiology of miliary TB. Considered to be predominantly a disease of infants and children in the pre-antibiotic era, miliary TB is increasingly being encountered in adults as well...
March 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28276834/drug-induced-liver-injury-due-to-antibiotics
#18
Einar S Björnsson
Drug-induced liver injury (DILI) is an important differential diagnosis in patients with abnormal liver tests and normal hepatobiliary imaging. Of all known liver diseases, the diagnosis of DILI is probably one of the most difficult one to be established. In all major studies on DILI, antibiotics are the most common type of drugs that have been reported. The clinical phenotype of different types of antibiotics associated with liver injury is highly variable. Some widely used antibiotics such as amoxicillin-clavulanate have been shown to have a delayed onset on liver injury and recently cefazolin has been found to lead to liver injury 1-3 weeks after exposure of a single infusion...
February 20, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28275295/investigation-of-mitigating-effect-of-colon-specific-prodrugs-of-boswellic-acid-on-2-4-6-trinitrobenzene-sulfonic-acid-induced-colitis-in-wistar-rats-design-kinetics-and-biological-evaluation
#19
Ajinkya Sarkate, Suneela S Dhaneshwar
AIM: To develop a colon-targeting bioreversible delivery system for β-boswellic acid (BBA) and explore utility of its prodrugs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. METHODS: Synthesis of 4 co-drugs of BBA with essential amino acids was achieved by CDI coupling, followed by their spectral characterization. In vitro kinetics were studied by HPLC in aqueous buffers, homogenates of gastrointestinal tract and fecal matter. In vivo kinetic studies were performed in Wistar rat plasma, urine and feces...
February 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28271527/the-role-of-lncrna-h19-in-gender-disparity-of-cholestatic-liver-injury-in-mdr2-mice
#20
Xiaojiaoyang Li, Runping Liu, Jing Yang, Lixin Sun, Luyong Zhang, Zhenzhou Jiang, Puneet Puri, Emily C Gurley, Guanhua Lai, Yuping Tang, Zhiming Huang, William M Pandak, Phillip B Hylemon, Huiping Zhou
The multi-drug resistance 2 knockout (Mdr2(-/-) ) mouse is a well-established model of cholestatic cholangiopathies. Female Mdr2(-/-) mice develop more severe hepatobiliary damage than male Mdr2(-/-) mice, which is correlated with a higher proportion of taurocholate (TCA) in bile. Although estrogen has been identified as an important player in intrahepatic cholestasis, the underlying molecular mechanisms of gender-based disparity of cholestatic injury remain unclear. The long non-coding RNA H19 is an imprinted, maternally expressed and estrogen-targeted gene, which is significantly induced in human fibrotic/cirrhotic liver and bile duct ligated mouse liver...
March 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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