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https://www.readbyqxmd.com/read/28092392/the-in-silico-identification-of-human-bile-salt-export-pump-abcb11-inhibitors-associated-with-cholestatic-drug-induced-liver-injury
#1
Lili Xi, Jia Yao, Yuhui Wei, Xin'an Wu, Xiaojun Yao, Huanxiang Liu, Shuyan Li
Drug-induced liver injury (DILI) is one of the major causes of drug attrition and failure. Currently, there is increasing evidence that direct inhibition of the human bile salt export pump (BSEP/ABCB11) by drugs and/or metabolites is one of the most important mechanisms of cholestatic DILI. In the present study, we employ two in silico methods, random forest (RF) and the pharmacophore method, to recognize potential BSEP inhibitors that could cause cholestatic DILI, with the aim of mitigating the risk of cholestatic DILI to some extent...
January 16, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28091407/clinical-characteristics-of-patients-with-drug-induced-liver-injury
#2
Li-Xia Yang, Cheng-Yuan Liu, Lun-Li Zhang, Ling-Ling Lai, Ming Fang, Chong Zhang
BACKGROUND: Drug is an important cause of liver injury and accounts for up to 40% of instances of fulminant hepatic failure. Drug-induced liver injury (DILI) is increasing while the diagnosis becomes more difficult. Though many drugs may cause DILI, Chinese herbal medicines have recently emerged as a major cause due to their extensive use in China. We aimed to provide drug safety information to patients and health carers by analyzing the clinical and pathological characteristics of the DILI and the associated drug types...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28089792/pharmacological-inhibition-of-pkc%C3%AE-counteracts-muscle-disease-in-a-mouse-model-of-duchenne-muscular-dystrophy
#3
V Marrocco, P Fiore, A Benedetti, S Pisu, E Rizzuto, A Musarò, L Madaro, B Lozanoska-Ochser, M Bouché
: Inflammation plays a considerable role in the progression of Duchenne Muscular Dystrophy (DMD), a severe muscle disease caused by a mutation in the dystrophin gene. We previously showed that genetic ablation of Protein Kinase C θ (PKCθ) in mdx, the mouse model of DMD, improves muscle healing and regeneration, preventing massive inflammation. To establish whether pharmacological targeting of PKCθ in DMD can be proposed as a therapeutic option, in this study we treated young mdx mice with the PKCθ inhibitor Compound 20 (C20)...
January 7, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28088913/a-comparative-study-of-short-term-efficacy-of-aripiprazole-and-risperidone-in-schizophrenia
#4
P B Sajeev Kumar, Ravi S Pandey, Jagadisha Thirthali, P T Siva Kumar, C Naveen Kumar
Objective To compare the short term anti-schizophrenic efficacy and side effect profile of aripiprazole with risperidone. Methodology The study was a non-randomized, naturalistic, rater blinded, prospective, 8-12 weeks, comparative trial between risperidone and aripiprazole in patients with schizophrenia. Patients already getting treatment with aripiprazole (10 to 30 mg/day) or risperidone (3 to 8mg/day) are recruited. Mini International Neuropsychiatric Interview (MINI) Plus, Positive and Negative Syndrome Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), Simpson Angus Scale (SAS), Udvalg for Klinske Undersogelser (UKU) Scale, Clinical Global Impression-severity scales were administered by principal investigator on the day of recruitment...
January 12, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28088257/clinical-and-experimental-research-in-antituberculosis-drug-induced-hepatotoxicity-a-review
#5
REVIEW
Udhaya Lavinya Baskaran, Evan Prince Sabina
Drug-induced liver injury is the common adverse effect seen in patients receiving antituberculosis drugs (ATDs). There are several risk factors associated with the development of hepatotoxicity in such patients. Though there have been appreciable efforts taken by carrying out studies investigating the efficacy of several natural and synthetic compounds in minimising this effect, the only choice available for clinicians is withdrawal of drugs. This review would give a precise idea of ATD-induced hepatotoxicity, its underlying mechanisms and alternative therapies for the same...
January 2017: Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28087864/drug-induced-weight-gain-rethinking-our-choices
#6
REVIEW
Katherine H Saunders, Leon I Igel, Alpana P Shukla, Louis J Aronne
Weight gain secondary to medications is a potentially modifiable risk. Here's how to optimize drug choices for patients with several common conditions.
November 2016: Journal of Family Practice
https://www.readbyqxmd.com/read/28087362/clinical-phenotypes-and-outcomes-of-heritable-and-sporadic-pulmonary-veno-occlusive-disease-a-population-based-study
#7
David Montani, Barbara Girerd, Xavier Jaïs, Marilyne Levy, David Amar, Laurent Savale, Peter Dorfmüller, Andrei Seferian, Edmund M Lau, Mélanie Eyries, Jérôme Le Pavec, Florence Parent, Damien Bonnet, Florent Soubrier, Elie Fadel, Olivier Sitbon, Gérald Simonneau, Marc Humbert
BACKGROUND: Bi-allelic mutations of the EIF2AK4 gene cause heritable pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis (PVOD/PCH). We aimed to assess the effect of EIF2AK4 mutations on the clinical phenotypes and outcomes of PVOD/PCH. METHODS: We did a population-based study using clinical, functional, and haemodynamic data from the registry of the French Pulmonary Hypertension Network. We reviewed the clinical data and outcomes from all patients referred to the French Referral Centre (Pulmonary Department, Hospital Kremlin-Bicêtre, University Paris-Sud) with either confirmed or highly probable PVOD/PCH with DNA available for mutation screening (excluding patients with other risk factors of pulmonary hypertension, such as chronic respiratory diseases)...
January 10, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28081264/the-important-role-of-lipid-raft-mediated-attachment-in-the-infection-of-cultured-cells-by-coronavirus-infectious-bronchitis-virus-beaudette-strain
#8
Huichen Guo, Mei Huang, Quan Yuan, Yanquan Wei, Yuan Gao, Lejiao Mao, Lingjun Gu, Yong Wah Tan, Yanxin Zhong, Dingxiang Liu, Shiqi Sun
Lipid raft is an important element for the cellular entry of some viruses, including coronavirus infectious bronchitis virus (IBV). However, the exact role of lipid rafts in the cellular membrane during the entry of IBV into host cells is still unknown. In this study, we biochemically fractionated IBV-infected cells via sucrose density gradient centrifugation after depleting plasma membrane cholesterol with methyl-β-cyclodextrin or Mevastatin. Our results demonstrated that unlike IBV non-structural proteins, IBV structural proteins co-localized with lipid raft marker caveolin-1...
2017: PloS One
https://www.readbyqxmd.com/read/28079848/high-resolution-computed-tomography-to-differentiate-chronic-diffuse-infiltrative-lung-diseases-with-chronic-multifocal-consolidation-patterns-using-logical-analysis-of-data
#9
Constance De Margerie-Mellon, Geneviève Dion, Julien Darlay, Imene Ridene, Marianne Kambouchner, Nadia Brauner, Michel Brauner, Dominique Valeyre, Pierre-Yves Brillet
BACKGROUND: Chronic lung consolidation has a limited number of differential diagnoses requiring distinct managements. The aim of the study was to investigate how logical analysis of data (LAD) can support their diagnosis at HRCT (high-resolution computed tomography). METHODS: One hundred twenty-four patients were retrospectively included and classified into 8 diagnosis categories: sarcoidosis (n=35), connective tissue disease (n=21), adenocarcinoma (n=17), lymphoma (n=13), cryptogenic organizing pneumonia (n=11), drug-induced lung disease (n=9), chronic eosinophilic pneumonia (n =7) and miscellaneous (n=11)...
December 23, 2016: Sarcoidosis, Vasculitis, and Diffuse Lung Diseases: Official Journal of WASOG
https://www.readbyqxmd.com/read/28079786/fatal-postoperative-systemic-pulmonary-hypertension-in-benfluorex-induced-valvular-heart-disease-surgery-a-case-report
#10
Christophe Baufreton, Patrick Bruneval, Marie-Christine Rousselet, Pierre-Vladimir Ennezat, Olivier Fouquet, Raphael Giraud, Carlo Banfi
RATIONALE: Drug-induced valvular heart disease (DI-VHD) remains an under-recognized entity. PATIENT CONCERNS: This report describes a heart valve replacement which was complicated by intractable systemic pulmonary arterial hypertension in a 61-year-old female with severe restrictive mitral and aortic disease. The diagnosis of valvular disease was preceded by a history of unexplained respiratory distress. The patient had been exposed to benfluorex for 6.5 years. DIAGNOSES: The diagnostic procedure documented specific drug-induced valvular fibrosis...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28079600/acute-administration-of-cyclosporine-a-does-not-impair-attention-or-memory-performance-in-healthy-men
#11
Anna L Kahl, Julia Kirchhof, Anna Füting, Bernd-Otto Hütter, Benjamin Wilde, Oliver Witzke, Sven Benson, Martin Hadamitzky, Manfred Schedlowski
There is clinical and experimental evidence that treatment with immunosuppressive and antiproliferative drugs such as the calcineurin inhibitor cyclosporine A (CsA) is associated with mental health problems and neuropsychological disturbances in patients. However, it remains unclear whether and to what extent cognitive functions such as memory and attention processes are affected by the pharmacological treatment. This is partly because of the fact that it is difficult to refer the observed neuropsychological disturbances in patients to the drug itself, to drug-induced immune suppression, or to interaction with other medication or comorbidities...
January 11, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28079589/in-vogue-ketamine-for-neuroprotection-in-acute-neurologic-injury
#12
Josh D Bell
Neurologic deterioration following acute injury to the central nervous system may be amenable to pharmacologic intervention, although, to date, no such therapy exists. Ketamine is an anesthetic and analgesic emerging as a novel therapy for a number of clinical entities in recent years, including refractory pain, depression, and drug-induced hyperalgesia due to newly discovered mechanisms of action and new application of its known pharmacodynamics. In this focused review, the evidence for ketamine as a neuroprotective agent in stroke, neurotrauma, subarachnoid hemorrhage, and status epilepticus is highlighted, with a focus on its applications for excitotoxicity, neuroinflammation, and neuronal hyperexcitability...
January 10, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28077644/ultrasensitive-hiv-1-p24-detects-single-infected-cells-and-differences-in-reservoir-induction-by-latency-reversal-agents
#13
Caroline Pereira Bittencourt Passaes, Timothée Bruel, Jérémie Decalf, Annie David, Mathieu Angin, Valerie Monceaux, Michaela Muller-Trutwin, Nicolas Noel, Katia Bourdic, Olivier Lambotte, Matthew L Albert, Darragh Duffy, Olivier Schwartz, Asier Sáez-Cirión
: The existence of HIV reservoirs in infected individuals under cART represents a major obstacle towards cure. Viral reservoirs are assessed by quantification of HIV nucleic acids, which does not discriminate between infectious and defective viruses, or by viral outgrowth assays, which requires large number of cells and long-term cultures. Here, we used an ultrasensitive p24 digital assay, which we report to be 1000 fold more sensitive than classical ELISA in the quantification of HIV-1 Gag p24 production in HIV-infected individuals samples...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077487/calcium-permeable-ampa-receptors-and-silent%C3%A2-synapses-in-cocaine-conditioned-place-preference
#14
Avani Shukla, Anna Beroun, Myrto Panopoulou, Peter A Neumann, Seth Gn Grant, M Foster Olive, Yan Dong, Oliver M Schlüter
Exposure to cocaine generates silent synapses in the nucleus accumbens (NAc), whose eventual unsilencing/maturation by recruitment of calcium-permeable AMPA-type glutamate receptors (CP-AMPARs) after drug withdrawal results in profound remodeling of NAc neuro-circuits. Silent synapse-based NAc remodeling was shown to be critical for several drug-induced behaviors, but its role in acquisition and retention of the association between drug rewarding effects and drug-associated contexts has remained unclear. Here, we find that the postsynaptic proteins PSD-93, PSD-95, and SAP102 differentially regulate excitatory synapse properties in the NAc...
January 11, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28076696/proton-pump-inhibitors-for-preventing-non-steroidal-anti-inflammatory-drug-induced-gastrointestinal-toxicity-a-systematic-review
#15
Man Yang, Min He, Miao Zhao, Bing Zou, Jun Liu, Ling-Min Luo, Qiu-Lan Li, Jun-Hui He, Ping-Guang Lei
OBJECTIVE: Proton pump inhibitors (PPIs) are recommended for preventing gastrointestinal lesions induced by non-steroidal anti-inflammatory drug (NSAID). We performed this study (1) to evaluate the effectiveness and safety of PPIs, (2) to explore the association between effectiveness and potential influential factors, and (3) to investigate the comparative effect of different PPIs. METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched to identify randomized controlled trials comparing different classes of PPIs, or comparing PPIs with placebo, H2 receptor antagonists or misoprostol in NSAIDs users...
January 11, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28074667/a-systematic-analysis-of-methylene-blue-for-drug-induced-shock-in-humans
#16
Anita Paula Tataru, Brandon J Warrick, Susan Smolinske
No abstract text is available yet for this article.
January 11, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28074467/systems-pharmacology-modeling-of-drug-induced-hyperbilirubinemia-differentiating-hepatotoxicity-and-inhibition-of-enzymes-transporters
#17
Kyunghee Yang, Christina Battista, Jeffrey L Woodhead, Simone H Stahl, Jerome T Mettetal, Paul B Watkins, Scott Q Siler, Brett A Howell
Elevations in serum bilirubin during drug treatment may indicate global liver dysfunction and a high risk of liver failure. However, drugs also can increase serum bilirubin in the absence of hepatic injury by inhibiting specific enzymes/transporters. We constructed a mechanistic model of bilirubin disposition based on known functional polymorphisms in bilirubin metabolism/transport. Using physiologically-based pharmacokinetic model-predicted drug exposure and enzyme/transporter inhibition constants determined in vitro, our model correctly predicted indinavir-mediated hyperbilirubinemia in humans and rats...
January 11, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28073321/in-response-to-a-systematic-analysis-of-methylene-blue-for-drug-induced-shock
#18
Stephen A Harding, Robert S Hoffman, David H Jang
No abstract text is available yet for this article.
January 11, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28073177/idiosyncratic-drug-induced-liver-injury-associated-with-bile-duct-loss-and-vanishing-bile-duct-syndrome-rare-but-has-severe-consequences
#19
EDITORIAL
Einar S Björnsson, Jon Gunnlaugur Jonasson
No abstract text is available yet for this article.
January 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28073113/in-vitro-to-in-vivo-extrapolation-for-drug-induced-liver-injury-using-a-pair-ranking-method
#20
Zhichao Liu, Hong Fang, Jürgen Borlak, Ruth Roberts, Weida Tong
Preclinical animal toxicity studies may not accurately predict human toxicity. In light of this, in vitro systems have been developed that have the potential to supplement or even replace animal use. We examined in vitro to in vivo extrapolation (IVIVE) of gene expression data obtained from The Open Japanese Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System (Open TG-GATEs) for 131 compounds given to rats for 28 days, and to human or rat hepatocytes for 24 hours. Notably, a Pair Ranking (PRank) method was developed to assess IVIVE potential with a PRank score based on the preservation of the order of similarity rankings of compound pairs between the platforms using a receiver operating characteristic (ROC) curve analysis to measure area under the curve (AUC)...
January 11, 2017: ALTEX
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