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Drug induced hepatitis

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https://www.readbyqxmd.com/read/28346810/an-automated-multiplexed-hepatotoxicity-and-cyp-induction-assay-using-heparg-cells-in-2d-and-3d
#1
Lindsey M Ott, Karthik Ramachandran, Lisa Stehno-Bittel
Drug-induced liver injury (DILI) and drug-drug interactions (DDIs) are concerns when developing safe and efficacious compounds. We have developed an automated multiplex assay to detect hepatotoxicity (i.e., ATP depletion) and metabolism (i.e., cytochrome P450 1A [CYP1A] and cytochrome P450 3A4 [CYP3A4] enzyme activity) in two-dimensional (2D) and three-dimensional (3D) cell cultures. HepaRG cells were cultured in our proprietary micromold plates and produced spheroids. HepaRG cells, in 2D or 3D, expressed liver-specific proteins throughout the culture period, although 3D cultures consistently exhibited higher albumin secretion and CYP1A/CYP3A4 enzyme activity than 2D cultures...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28339489/human-subtilisin-kexin-isozyme-1-ski-1-site-1-protease-s1p-regulates-cytoplasmic-lipid-droplet-abundance-a-potential-target-for-indirect-acting-anti-dengue-virus-agents
#2
Anastasia Hyrina, Fanrui Meng, Steven J McArthur, Sharlene Eivemark, Ivan R Nabi, François Jean
Viral hijacking and manipulation of host-cell biosynthetic pathways by human enveloped viruses are shared molecular events essential for the viral lifecycle. For Flaviviridae members such as hepatitis C virus and dengue virus (DENV), one of the key subsets of cellular pathways that undergo manipulation is the lipid metabolic pathways, underlining the importance of cellular lipids and, in particular, lipid droplets (LDs) in viral infection. Here, we hypothesize that targeting cellular enzymes that act as key regulators of lipid homeostasis and LD formation could represent a powerful approach to developing a novel class of broad-spectrum antivirals against infection associated with all DENV serotypes (1-4) circulating around the world...
2017: PloS One
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
#3
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/28336160/unexpected-drug-induced-raynaud-phenomenon-analysis-from-the-french-national-pharmacovigilance-database
#4
Émilie Bouquet, Geoffrey Urbanski, Christian Lavigne, Pascale Lainé-Cessac
OBJECTIVE: To estimate the association between exposure to medicinal products and Raynaud phenomenon. METHODS: The study used the data of all adverse drug reactions notified to the French national pharmacovigilance database. All cases reported between 1st January 1995 and 10th December 2012 were selected. A case/non-case method was used to measure disproportionality of the association between drug exposure and Raynaud phenomenon. The cases concerned all observations involving Raynaud phenomenon...
February 22, 2017: Thérapie
https://www.readbyqxmd.com/read/28335764/health-care-cost-associated-with-the-use-of-enzyme-inducing-and-non-enzyme-active-antiepileptic-drugs-in-the-uk-a-long-term-retrospective-matched-cohort-study
#5
Simon Borghs, Solène Thieffry, Matthias Noack-Rink, Peter Dedeken, Lai San Hong, Laura Byram, John Logan, Jane Chan, Victor Kiri
BACKGROUND: Some antiepileptic drugs (AEDs) induce expression of hepatic enzymes. This can contribute to comorbidities via interference with metabolic pathways and concomitant drug metabolization, thereby increasing the likelihood of health care interventions. Using medical records, we compared the direct health care cost in patients initiating epilepsy therapy with enzyme-inducing AEDs (EIAEDs) vs non-enzyme-active AEDs (nEAAEDs) over up to 12 years. METHODS: Patients with untreated epilepsy were indexed in the UK Clinical Practice Research Datalink and Hospital Episode Statistics database when prescribed a new EIAED or nEAAED between January 2001 and December 2010...
March 23, 2017: BMC Neurology
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
#6
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/28333153/a-novel-inhibitor-idpp-interferes-with-entry-and-egress-of-hcv-by-targeting-glycoprotein-e1-in-a-genotype-specific-manner
#7
Myungeun Lee, Jaewon Yang, Eunji Jo, Ji-Young Lee, Hee-Young Kim, Ralf Bartenschlager, Eui-Cheol Shin, Yong-Soo Bae, Marc P Windisch
Despite recent advances in curing chronic hepatitis C (CHC), the high economic burden to therapy, viral drug resistance, difficult to treat hepatitis C virus (HCV) genotypes and patient groups are still of concern. To address this unmet medical needs, we devised strategies to identify novel viral interventions through target-free high-throughput screening of small molecules utilizing a phenotypic-based HCV infection assay. Thereby, a very potent (EC50 46 ± 26 pM) iminodipyridinopyrimidine (IDPP) drug candidate was selected, and confirmed in primary human hepatocytes (EC50 0...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28333073/effects-of-melatonin-on-liver-injuries-and-diseases
#8
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/28327789/prevalence-of-hepatitis-c-virus-and-human-immunodeficiency-virus-in-a-group-of-patients-newly-diagnosed-with-active-tuberculosis-in-porto-alegre-southern-brazil
#9
Cintia Costi, Tarciana Grandi, Maria Laura Halon, Márcia Susana Nunes Silva, Cláudia Maria Dornelles da Silva, Tatiana Schäffer Gregianini, Lia Gonçalves Possuelo, Carla Adriane Jarczewski, Christian Niel, Maria Lucia Rosa Rossetti
BACKGROUND: Porto Alegre is the Brazilian state capital with second highest incidence of tuberculosis (TB) and the highest proportion of people infected with human immunodeficiency virus (HIV) among patients with TB. Hepatitis C virus (HCV) infection increases the risk of anti-TB drug-induced hepatotoxicity, which may result in discontinuation of the therapy. OBJECTIVES: The aim of this study was (i) to estimate prevalence of HCV and HIV in a group of patients newly diagnosed with active TB in a public reference hospital in Porto Alegre and (ii) to compare demographic, behavioural, and clinical characteristics of patients in relation to their HCV infection status...
April 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28324653/evaluation-of-brain-pharmacokinetic-and-neuropharmacodynamic-attributes-of-antiepileptic-drug-lacosamide-in-hepatic-and-renal-impairment-preclinical-evidence
#10
Baldeep Kumar, Manish Modi, Biman Saikia, Bikash Medhi
The knowledge of pharmacokinetic and pharmacodynamic properties of antiepileptic drugs is helpful in optimizing drug therapy for epilepsy. This study was designed to evaluate the pharmacokinetic and pharmacodynamic properties of lacosamide in experimentally induced hepatic and renal impairment in seizure animals. Hepatic or renal impairment was induced by injection of carbon tetrachloride or diclofenac sodium, respectively. After induction, the animals were administered with a single dose of lacosamide. At different time points, MES seizure recordings were done followed by isolation of plasma and brain samples for drug quantification and pharmacodynamic measurements...
March 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28321390/metabonomics-research-progress-on-liver-diseases
#11
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
#12
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/28320086/antifibrotic-effect-of-diethylcarbamazine-combined-with-hesperidin-against-ethanol-induced-liver-fibrosis-in-rats
#13
Alaa El-Din El-Sayed El-Sisi, Samia Salim Sokar, Abdelhadi Mohamed Shebl, Dina Zakaria Mohamed
Chronic alcohol consumption leads to extracellular matrix hyperplasia and liver fibrosis with a great role of hepatic stellate cell (HSC) activation in this process. The present study was designed to investigate the possible protective effects of diethylcarbamazine (DEC) (50mg/kg, acting as an anti-inflammatory drug, interferes with the arachidonic acid metabolism) when administrated in combination with hesperidin (HDN) (200mg/kg, a flavanone glycoside with potent antioxidant and anti-inflammatory activities) against alcoholic liver fibrosis in wistar rats compared to silymarin (Sil) (100mg/kg)...
March 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28317886/systems-pharmacology-based-strategy-to-screen-new-adjuvant-for-hepatitis-b-vaccine-from-traditional-chinese-medicine-ophiocordyceps-sinensis
#14
Jingbo Wang, Rui Liu, Baoxiu Liu, Yan Yang, Jun Xie, Naishuo Zhu
Adjuvants are common component for many vaccines but there are still few licensed for human use due to low efficiency or side effects. The present work adopted Systems Pharmacology analysis as a new strategy to screen adjuvants from traditional Chinese medicine. Ophiocordyceps sinensis has been used for many years in China and other Asian countries with many biological properties, but the pharmacological mechanism has not been fully elucidated. First in this study, 190 putative targets for 17 active compounds in Ophiocordyceps sinensis were retrieved and a systems pharmacology-based approach was applied to provide new insights into the pharmacological actions of the drug...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317117/comparative-pharmacokinetic-evaluation-of-lopinavir-and-lopinavir-loaded-solid-lipid-nanoparticles-in-hepatic-impaired-rat-model
#15
Punna Rao Ravi, Rahul Vats
OBJECTIVE: Drug-induced hepatotoxicity is a major cause of concern in patients receiving HIV/TB co-treatment. Lopinavir (LPV), an anti-HIV drug, shows poor plasma exposure due to hepatic first-pass metabolism. In this study, we investigated the effect of hepatotoxicity on pharmacokinetics of free LPV and LPV-loaded solid lipid nanoparticles (LPV SLNs) in male Wistar rats. METHODS: Hepatic impairment model in rats was developed by injecting CCl4 (i.p., 2 ml/kg). Comparative pharmacokinetic (n = 5) and tissue distribution studies (n = 3) were conducted following oral administration (20 mg/kg) of free LPV and LPV SLNs in normal and hepatic impaired rats...
March 19, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28315916/muscular-damage-in-a-patient-with-hepatitis-b-induced-by-beta-l-2-deoxythymidine-and-detected-by-18-f-fdg-pet-ct
#16
Jinhua Zi, Changyun Xu, Xuemei Zhang
A 58 years old man under 2'-Deoxy-L-thymidine treatment for his hepatitis B was admitted to our hospital complaining for the last 2 months of recurrent upper abdomen discomfort, fatigue and weight loss of 10 kilograms and general muscular soreness, for 2 weeks. He had elevated creatine kinase (CK), myoglobin, CK-MB and other related or common laboratory findings. Fluorine-18- fluorodeoxyglucose positron emission tomography/ computed tomography ((18)F-FDG PET/CT) showed a diffuse, homogenous, moderately elevated glucose uptake in all muscle groups...
March 20, 2017: Hellenic Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28315874/multiple-drug-hypersensitivity
#17
Werner J Pichler, Yuttana Srinoulprasert, James Yun, Oliver Hausmann
Multiple drug hypersensitivity (MDH) is a syndrome that develops as a consequence of massive T-cell stimulations and is characterized by long-lasting drug hypersensitivity reactions (DHR) to different drugs. The initial symptoms are mostly severe exanthems or drug rash with eosinophilia and systemic symptoms (DRESS). Subsequent symptoms due to another drug often appear in the following weeks, overlapping with the first DHR, or months to years later after resolution of the initial presentation. The second DHR includes exanthema, erythroderma, DRESS, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hepatitis, and agranulocytosis...
March 18, 2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/28315483/functional-proteomic-analysis-of-corticosteroid-pharmacodynamics-in-rat-liver-relationship-to-hepatic-stress-signaling-energy-regulation-and-drug-metabolism
#18
Vivaswath S Ayyar, Richard R Almon, Debra C DuBois, Siddharth Sukumaran, Jun Qu, William J Jusko
Corticosteroids (CS) are anti-inflammatory agents that cause extensive pharmacogenomic and proteomic changes in multiple tissues. An understanding of the proteome-wide effects of CS in liver and its relationships to altered hepatic and systemic physiology remains incomplete. Here, we report the application of a functional pharmacoproteomic approach to gain integrated insight into the complex nature of CS responses in liver in vivo. An in-depth functional analysis was performed using rich pharmacodynamic (temporal-based) proteomic data measured over 66h in rat liver following a single dose of methylprednisolone (MPL)...
March 14, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28302559/in-vitro-monoamine-oxidase-inhibition-potential-of-alpha-methyltryptamine-analog-new-psychoactive-substances-for-assessing-possible-toxic-risks
#19
Lea Wagmann, Simon D Brandt, Pierce V Kavanagh, Hans H Maurer, Markus R Meyer
Tryptamines have emerged as new psychoactive substances (NPS), which are distributed and consumed recreationally without preclinical studies or safety tests. Within the alpha-methylated tryptamines, some of the psychoactive effects of the prototypical alpha-methyltryptamine (AMT) have been described decades ago and a contributing factor of its acute toxicity appears to involve the inhibition of monoamine oxidase (MAO). However, detailed information about analogs is scarce. Therefore, thirteen AMT analogs were investigated for their potential to inhibit MAO...
March 13, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28296768/difficult-clinical-management-of-antituberculosis-dress-syndrome-complicated-by-mrsa-infection-a-case-report
#20
Li Wang, Lin-Feng Li
RATIONALE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe drug-induced hypersensitivity reaction characterized by skin rash, fever, blood abnormalities, and multiple organ involvement. The diagnosis of DRESS syndrome is often delayed because of its variable presentation. Prompt withdrawal of the culprit drug is the definitive treatment. DRESS syndrome induced by antituberculosis drugs has rarely been reported. PATIENT CONCERNS: A 50-year-old man admitted to our hospital with recurrent episodes of progressive rash, fever, eosinophilia, lymphadenopathy, hepatic, and pulmonary involvement were experienced after repeat trials of the same antituberculosis drugs...
March 2017: Medicine (Baltimore)
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