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Drug induced liver disease

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https://www.readbyqxmd.com/read/29235390/mir-122-and-other-micrornas-as-potential-circulating-biomarkers-of-drug-induced-liver-injury
#1
Lawrence S Howell, Lucy Ireland, B Kevin Park, Christopher E Goldring
Drug-induced liver injury (DILI) is a severe adverse drug reaction which is of major concern to patients, clinicians and the pharmaceutical industry. Accurate and rapid detection of DILI is important for patient stratification and treatment in the clinic and benefits pre-clinical drug design and risk assessment. MicroRNAs (miRNAs) offer a potential new and improved class of circulating biomarkers of DILI over the current gold standard biomarkers. Areas covered: This review highlights the shortcomings of the currently used panel of biomarkers and how miRNAs, primarily miR-122, show an improved level of specificity and sensitivity in the prediction of DILI...
December 13, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29234281/interleukin-6-induces-dec1-promotes-dec1-interaction-with-rxr%C3%AE-and-suppresses-the-expression-of-pxr-car-and-their-target-genes
#2
Rui Ning, Yunran Zhan, Shuangcheng He, Jinhua Hu, Zhu Zhu, Gang Hu, Bingfang Yan, Jian Yang, Wei Liu
Inflammatory burden is a primary cellular event in many liver diseases, and the overall capacity of drug elimination is decreased. PXR (pregnane X receptor) and CAR (constitutive androstane receptor) are two master regulators of genes encoding drug-metabolizing enzymes and transporters. DEC1 (differentiated embryonic chondrocyte-expressed gene 1) is a ligand-independent transcription factor and reportedly is induced by many inflammatory cytokines including IL-6. In this study, we used primary hepatocytes (human and mouse) as well as HepG2 cell line and demonstrated that IL-6 increased DEC1 expression and decreased the expressions of PXR, CAR, and their target genes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29224736/a-natural-small-molecule-inhibitor-corilagin-blocks-hcv-replication-and-modulates-oxidative-stress-to-reduce-liver-damage
#3
B Uma Reddy, Ranajoy Mullick, Anuj Kumar, Geetika Sharma, Paromita Bag, Chaitrali Laha Roy, Govindarajan Sudha, Himani Tandon, Pratik Dave, Asutosh Shukla, Priyanka Srinivasan, Madhusudhan Nandhitha, Narayanaswamy Srinivasan, Saumitra Das
Hepatitis C virus (HCV) infection causes chronic liver disease, which often leads to hepatocellular carcinoma. Earlier, we have demonstrated anti-HCV property of the methanolic extract of Phyllanthus amarus, an age-old folk-medicine against viral hepatitis. Here, we report identification of a principal bioactive component 'corilagin', which showed significant inhibition of the HCV key enzymes, NS3 protease and NS5B RNA-dependent-RNA-polymerase. This pure compound could effectively inhibit viral replication in the infectious cell culture system, displayed strong antioxidant activity by blocking HCV induced generation of reactive oxygen species and suppressed up-regulation of NOX4 and TGF-β mRNA levels...
December 7, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29224108/negative-impact-of-testosterone-deficiency-and-5%C3%AE-reductase-inhibitors-therapy-on-metabolic-and-sexual-function-in-men
#4
Abdulmaged M Traish
Androgens are steroid hormones with pleotropic and diverse biochemical and physiological functions, and androgen deficiency exerts a negative impact on human health. Testosterone (T) either directly or via its transformation into the more potent metabolite 5α-dihydrotestosterone (5α-DHT) or via aromatization into estradiol (E2) modulates important biochemical signaling pathways of human physiology and plays a critical role in the growth and/or maintenance of functions in a host of tissues and organs. T and 5α-DHT play an important role in regulating physiology of the muscle, adipose tissue, liver, bone, and central nervous system, as well as reproductive and sexual functions...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29209440/efficacy-of-fenugreek-based-bionanocomposite-on-renal-dysfunction-and-endogenous-intoxication-in-high-calorie-diet-induced-obesity-rat-model-comparative-study
#5
Victoria V Konopelniuk, Ievgenii I Goloborodko, Tetyana V Ishchuk, Tetyana B Synelnyk, Ludmila I Ostapchenko, Mykola Ya Spivak, Rostyslav V Bubnov
Background: Worldwide obesity spread is a global health problem and needs to be further studied. Co-morbidities of obesity include insulin resistance, diabetes mellitus type 2, and dyslipidemia, which are the most frequent contributing factors for metabolic syndrome (MetS), as well as non-alcoholic fatty liver disease and chronic kidney disease. The aim was to study renal function and endogenous intoxication panel on high-calorie diet-induced obesity rat model and perform comparative study of the treatment efficacy of Fenugreek-based bionanocomposite vs antiobesogenic drugs (Orlistat)...
December 2017: EPMA Journal
https://www.readbyqxmd.com/read/29201931/colchicine-induced-hepatotoxicity
#6
Collette E Abbott, Ruliang Xu, Samuel H Sigal
Drug-induced injury (DILI) is a frequent cause of abnormal liver tests and a leading cause of liver failure in the United States. Colchicine has long been used as a systemic anti-inflammatory agent for treatment of gout by inhibiting mitotic activity and neutrophil function. We present the first case of colchicine-induced hepatoxicity, supported by histopathologic findings characteristic of colchicine-induced injury and resolution of liver enzyme abnormalities after its discontinuation. Colchicine-associated DILI has implications for the evaluation of patients with abnormal liver tests and gout, especially for patients with alcoholism and non-alcoholic fatty liver disease, in whom there is an increased incidence of gout...
2017: ACG Case Reports Journal
https://www.readbyqxmd.com/read/29201778/liver-disease-in-sri-lanka
#7
REVIEW
Hasitha S Wijewantha
Liver disease in Sri Lanka is mainly due to alcoholic liver disease and nonalcoholic fatty liver disease. In contrast to other South Asian countries, the prevalence of hepatitis B and C is low in Sri Lanka and prevalence of hepatitis A is intermediate. The few reported cases of hepatitis E in Sri Lanka are mainly in people who have traveled to neighboring South Asian countries. Wilson's disease, autoimmune hepatitis, hemochromatosis, drug-induced liver disease, and primary biliary cirrhosis are recognized causes of liver disease in Sri Lanka...
January 2017: Euroasian Journal of Hepato-Gastroenterology
https://www.readbyqxmd.com/read/29198698/successful-intravenous-immunoglobulin-treatment-in-pediatric-severe-dress-syndrome
#8
Nufar Marcus, Keren Smuel, Moran Almog, Dario Prais, Rachel Straussberg, Daniel Landau, Oded Scheuerman
BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, potentially life-threatening delayed drug-induced hypersensitivity reaction. The most frequently reported drugs causing DRESS are aromatic antiepileptic agents. Prompt withdrawal of the offending drug and administering systemic corticosteroids is the most widely accepted and used treatment. The treatment of severe DRESS not responsive to systemic corticosteroids is uncertain. OBJECTIVE: The objective of this study was to describe a case series of pediatric patients with DRESS who were treated successfully with intravenous immunoglobulins (IVIGs)...
November 30, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/29194686/new-insights-into-the-role-and-mechanism-of-c-jun-n-terminal-kinase-signaling-in-the-pathobiology-of-liver-diseases
#9
REVIEW
Sanda Win, Tin Aung Than, Jun Zhang, Christina Oo, Robert Win Maw Min, Neil Kaplowitz
Mitogen-activated protein kinase (MAPK) signaling in the liver occurs in response to physical and chemical stress, including alterations in nutrients, growth factors, cytokines, extracellular matrix, DNA damage, drugs and toxins. This signaling pathway plays a role in liver injury and diseases such as drug induced hepatotoxicity, viral hepatitis, infection and inflammation, NAFLD, NASH, ALD, ischemia/reperfusion, fibrosis, regeneration, and carcinogenesis (1-4). In mammals, three major groups of MAPK have been identified...
November 30, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29192646/development-of-a-novel-histologic-diagnostic-algorithm-for-hepatic-graft-versus-host-disease
#10
Ashley E Stueck, Thomas D Schiano, M Isabel Fiel
The histopathologic diagnosis of hepatic graft-versus-host disease post bone marrow and stem cell transplantation can be challenging, but timely and unambiguous diagnosis is essential for appropriate patient management. To address this diagnostic dilemma, we identified histologic features specific for hepatic graft-versus-host disease and developed a diagnostic algorithm. Two hepatopathologists blindly evaluated 40 liver biopsies from patients with clinically and biologically confirmed graft-versus-host disease, as well as 44 controls, for percent bile duct loss, bile duct damage, intraepithelial lymphocytes, ductular reaction, acidophilic bodies/10 high power fields (HPF), cholestasis, portal and lobular inflammation, and endotheliitis...
December 1, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29185238/agreement-among-different-scales-for-causality-assessment-in-drug-induced-liver-injury
#11
Saibal Das, Sapan K Behera, Alphienes S Xavier, Srinivas Velupula, Steven A Dkhar, Sandhiya Selvarajan
BACKGROUND AND OBJECTIVE: The causality assessment of drug-induced liver injury (DILI) remains a challenge and eagerly awaits the development of reliable hepatotoxicity biomarkers. None of the different available algorithms used for the causality assessment of DILI has been universally accepted as the gold standard. This study was conducted to examine the agreement among different causality assessment scales in reporting DILI. METHODS: The World Health Organization-Uppsala Monitoring Center (WHO-UMC), Naranjo, Roussel Uclaf Causality Assessment Method (RUCAM), Maria & Victorino (M & V) and Digestive Disease Week-Japan (DDW-J) assessment scales were used to compare the causalities in all the reported cases of DILI in our adverse drug reaction (ADR) monitoring centre from January 2014 to June 2017...
November 28, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29180018/isoliquiritigenin-protects-against-sepsis-induced-lung-and-liver-injury-by-reducing-inflammatory-responses
#12
Xiong Chen, Xueding Cai, Rongrong Le, Man Zhang, Xuemei Gu, Feixia Shen, Guangliang Hong, Zimiao Chen
Sepsis, one of the most fatal diseases worldwide, often leads to multiple organ failure, mainly due to uncontrolled inflammatory responses. Despite accumulating knowledge obtained in recent years, effective drugs to treat sepsis in the clinic are still urgently needed. Isoliquiritigenin (ISL), a chalcone compound, has been reported to exert anti-inflammatory properties. However, little is known about the effects of ISL on sepsis and its related complications. In this study, we investigated the potential protective effects of ISL on lipopolysaccharide (LPS)-induced injuries and identified the mechanisms underlying these effects...
November 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29179597/spontaneous-extradural-hematoma-a-rare-entity
#13
Khursheed Alam Khan, Sachin Chhabra, Somnath Sharma, Devendra Purohit
Spontaneous onset extradural hematoma (EDH) is a very rare entity and has been seen mostly to be associated with adjacent infective pathologies, dural vascular malformations, extradural metastasis, or coagulopathies. We report a series of two such cases and review the literature. One case presented with spontaneous EDH that was managed conservatively and was diagnosed to have chronic kidney disease later; the other had deranged coagulation profile and liver function secondary to drug induced hepatitis and was operated...
November 28, 2017: British Journal of Neurosurgery
https://www.readbyqxmd.com/read/29175112/chalcones-as-putative-hepatoprotective-agents-preclinical-evidence-and-molecular-mechanisms
#14
REVIEW
Elham Karimi Sales, Gisou Mohaddes, Mohammad Reza Alipour
Chalcones form an important group of natural compounds and flavonoid precursors which are abundant in fruits, vegetables, and edible plants. These compounds have many beneficial properties including anti-inflammatory, anti-microbial, antioxidant, anti-cancer, anti-amyloid, anti-diabetic, anti-obesity, hypolipidemic, and cytoprotective. Chalcone derivatives have protective effects on the liver in nonalcoholic fatty liver disease, alcoholic fatty liver, drug- and toxicant-induced liver injury, and liver cancer through several mechanisms...
November 22, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29174039/lavatera-critica-a-green-leafy-vegetable-controls-high-fat-diet-induced-hepatic-lipid-accumulation-and-oxidative-stress-through-the-regulation-of-lipogenesis-and-lipolysis-genes
#15
Chinnadurai Veeramani, Mohammed A Alsaif, Khalid S Al-Numair
BACKGROUND: Lipid accumulation is the most vital risk factor for inducing nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. Thus, the development of novel drugs is urgently needed to control obesity related diseases. OBJECTIVE: Here, we investigated the protective role of Lavatera critica (LC), a green vegetable, in male C57BL/6J mice fed with high fat (HF) diet for 10 weeks to induce hepatic lipid accumulation and oxidative cellular damage. RESULTS: After oral administration of chloroform (CFLC), ethyl acetate (EFLC), or methanol (MFLC) fractions of Lavatera critica to the HF group, EALC alone significantly reduced the activities of hepatic markers such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST); moreover, the results showed that 50 mg/kg dose has the maximum activity...
November 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29171940/human-leukocyte-antigens-key-regulators-of-t-cell-mediated-drug-hypersensitivity
#16
REVIEW
A J Redwood, R K Pavlos, K D White, E J Phillips
Adverse drug reactions (ADR) can be broadly categorised as either on-target or off-target. On-target ADRs arise as a direct consequence of the pharmacological properties of the drug and are therefore predictable and dose dependant. On-target ADRs comprise the majority (>80%) of ADRs, relate to the drug's interaction with its known pharmacological target and are a result of a complex interplay of genetic and ecologic factors. In contrast off-target ADRs, including immune mediated ADRs (IM-ADRs), are due to unintended pharmacological interactions such as inadvertent ligation of host cell receptors or non-pharmacological interactions mediated through an adaptive immune response...
November 24, 2017: HLA
https://www.readbyqxmd.com/read/29171218/-discussion-on-influence-factors-mechanism-and-traditional-chinese-medicine-pathogenesis-of-idiosyncratic-drug-induced-liver-injury
#17
Gang Wang, Ying Liu, Xue-Feng Hou, Jie Song, Hui-Hui Qiu, Qing-Xiang Zhong, Xiao-Bin Jia, Fu-Jing Wang, Nan Jiang, Zhong-Cheng Ke, Liang Feng
Idiosyncratic drug-induced liver injury (IDILI) is a kind of unique adverse drug reaction with relative high morbidity compared with other idiosyncratic diseases. Its occurrence, however, has nothing to do with pharmacological effects and clinical dosage of drugs administered, and only a small number of susceptible individuals will suffer from it. Especially to deserve to be mentioned, the proportion of TCM-induced IDILI showed an ascending trend year by year. So in this article, the author has reviewed some facts related with TCM-induced IDILI, including the predisposing causes and occurrence mechanism, and tries to provide reference for the prevention, diagnosis and treatment of TCM-induced IDILI through the analysis of characteristics and research status of TCM-induced IDILI and exploration of the internal relationship between Chinese medicine constitution type and IDILI...
August 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29170554/mechanotransduction-modulated-fibrotic-microniches-reveal-the-contribution-of-angiogenesis-in-liver-fibrosis
#18
Longwei Liu, Zhifeng You, Hongsheng Yu, Lyu Zhou, Hui Zhao, Xiaojun Yan, Dulei Li, Bingjie Wang, Lu Zhu, Yuzhou Xu, Tie Xia, Yan Shi, Chenyu Huang, Wei Hou, Yanan Du
The role of pathological angiogenesis on liver fibrogenesis is still unknown. Here, we developed fibrotic microniches (FμNs) that recapitulate the interaction of liver sinusoid endothelial cells (LSECs) and hepatic stellate cells (HSCs). We investigated how the mechanical properties of their substrates affect the formation of capillary-like structures and how they relate to the progression of angiogenesis during liver fibrosis. Differences in cell response in the FμNs were synonymous of the early and late stages of liver fibrosis...
December 2017: Nature Materials
https://www.readbyqxmd.com/read/29169803/expression-purification-and-characterization-of-two-leucine-aminopeptidases-of-the-blood-fluke-schistosoma-mansoni
#19
Gabriela Maggioli, Gabriel Rinaldi, Ines Giaudrone, Patricia Berasain, José F Tort, Paul J Brindley, Carlos Carmona
Schistosomiasis is a major neglected tropical disease (NTD) and considered the most important of the human helminthiases in terms of morbidity and mortality. Whereas treatment with praziquantel has been effective since the 1980s, the potential for the emergence of drug resistance has propelled the search for new interventions. Studies have revealed key roles of proteases in parasitic helminths during establishment of infection, tissue invasion, immune evasion, parasite feeding and development throughout the different developmental stages, pinpointing them as possible candidates...
November 20, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/29167318/trail-reduces-impaired-glucose-tolerance-and-nafld-in-the-high-fat-diet-fed-mouse
#20
Stella Bernardi, Barbara Toffoli, Veronica Tisato, Fleur Bossi, Stefania Biffi, Andrea Lorenzon, Giorgio Zauli, Paola Secchiero, Bruno Fabris
AIMS/HYPOTHESIS: Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis-inducing ligand) may have an important role in the treatment of type 2 diabetes. It has been shown that TRAIL deficiency worsens diabetes and that TRAIL delivery, when it is given before disease onset, slows down its development. This study aimed at evaluating whether TRAIL had the potential to treat type 2 diabetes. METHODS: Thirty male C57BL/6J mice were randomized to a standard or a high-fat diet (HFD)...
November 22, 2017: Clinical Science (1979-)
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