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https://www.readbyqxmd.com/read/28724039/treatment-of-digital-ulcers-in-systemic-sclerosis-case-series-study-of-thirteen-patients-and-discussion-on-outcome
#1
Yahia Abuowda, Raquel Sousa Almeida, Ana Alves Oliveira, Petra Pego, Cristina Santos, João Matos-Costa
Introduction: In systemic sclerosis (SSc), digital ulcers (DU) are debilitating and recurrent. They are markers of prognosis and are associated with disability and mortality. Treatment strategies have been developed to block the proposed mechanisms of this complication. Objective: Clinical description of a population of SSc patients with DU, treatment, complications and outcome. Method: Analysis of 48 SSc patients meeting 2013 ACR-EULAR criteria, followed between 1999-2015; 13 patients had DU...
May 2017: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/28717109/utility-of-human-hepatocyte-spheroids-without-feeder-cells-for-evaluation-of-hepatotoxicity
#2
Takuo Ogihara, Hiroshi Arakawa, Tomoko Jomura, Yoko Idota, Satoshi Koyama, Kentaro Yano, Hajime Kojima
We investigated the utility of three-dimensionally cultured hepatocytes (spheroids) without feeder cells (Sph(f-)) for the prediction of drug-induced liver injury (DILI) in humans. Sph(f-) and spheroids cultured on feeder cells (Sph(f+)) were exposed to the hepatotoxic drugs flutamide, diclofenac, isoniazid and chlorpromazine at various concentrations for 14 days, and albumin secretion and cumulative leakages of toxicity marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GTP), were measured...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28717103/metabolomics-of-an-in-vitro-liver-model-containing-primary-hepatocytes-assembling-around-an-endothelial-cell-network-comparative-study-on-the-metabolic-stability-and-the-effect-of-acetaminophen-treatment
#3
Yu Toyoda, Kasumi Kashikura, Tomoyoshi Soga, Yoh-Ichi Tagawa
Recently, a novel culture system consisting of primary hepatocytes structured over a network of endothelial cells on the Engelbreth-Holm-Swarm (EHS) gel has been reported. This in vitro liver model on the EHS gel (IVLEHS) has been shown to maintain the expression of hepatic genes and their functional activity. Moreover, the IVLEHS was more sensitive to xenobiotics than hepatocyte monocultures, suggesting the potential utility of this culture system for compound hepatotoxicity screening. However, the effect of this three-dimensional structure formation on the cellular metabolic profile of hepatocytes in the IVLEHS is not well understood...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28714419/design-of-multi-target-agents-for-the-treatment-of-alzheimer-s-disease-based-on-tacrine
#4
Hongzhi Lin, Qi Li, Kai Gu, Jie Zhu, Xueyang Jiang, Yao Chen, Haopeng Sun
Alzheimer's disease (AD) is one of the most common forms of dementia in elderly people. To date, efficacious therapeutic agent for the treatment of AD is still very limited, so it has long been a challenging and attractive task to discover new anti-AD drugs. Considering the multifactorial nature of AD, recently, the concept of multi-target-directed ligands (MTDLs) has emerged as a new strategy for designing therapeutic agents on AD. MTDLs are believed to exert their effects through simultaneously affecting multiple targets which contribute to etiology of AD...
July 17, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28714083/acute-liver-failure-with-amiodarone-infusion-a-case-report-and-systematic-review
#5
P Jaiswal, B M Attar, J E Yap, K Devani, R Jaiswal, Y Wang, R Szynkarek, D Patel, M Demetria
WHAT IS KNOWN AND OBJECTIVE: Amiodarone, a commonly used class III antiarrhythmic agent notable for a relatively long half-life of up to 6 months and its pronounced adverse effect profile, is used for both acute and chronic management of cardiac arrhythmias. Chronic use of amiodarone has been associated with asymptomatic hepatotoxicity; however, acute toxicity is thought to be uncommon. There are only six reported cases of acute liver failure (ALF) secondary to amiodarone. In all these cases the outcome of death during the same hospitalization resulted...
July 16, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28713372/nanoparticle-formulated-curcumin-prevents-posttherapeutic-disease-reactivation-and-reinfection-with-mycobacterium-tuberculosis-following-isoniazid-therapy
#6
Sultan Tousif, Dhiraj Kumar Singh, Sitabja Mukherjee, Shaheer Ahmad, Rakesh Arya, Ranjan Nanda, Anand Ranganathan, Maitree Bhattacharyya, Luc Van Kaer, Santosh K Kar, Gobardhan Das
Curcumin, the bioactive component of turmeric also known as "Indian Yellow Gold," exhibits therapeutic efficacy against several chronic inflammatory and infectious diseases. Even though considered as a wonder drug pertaining to a myriad of reported benefits, the translational potential of curcumin is limited by its low systemic bioavailability due to its poor intestinal absorption, rapid metabolism, and rapid systemic elimination. Therefore, the translational potential of this compound is specifically challenged by bioavailability issues, and several laboratories are making efforts to improve its bioavailability...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28710607/evaluation-of-a-food-and-drug-administration-mandate-to-limit-acetaminophen-in-prescription-combination-products
#7
David Goldberger, David Vearrier
INTRODUCTION: In 2014, the US Food and Drug Administration limited the production of prescription acetaminophen-opioid combination products to 325 mg per dose unit. The goal of this mandate was to decrease the likelihood of unintentional acetaminophen hepatotoxicity. This study was designed to determine if this federal regulation has succeeded in reducing unintentional acetaminophen-induced hepatotoxicity from opioid combination products. METHODS: Using data from the National Poison Data System (NPDS), we analyzed all calls to US Poison Control Centers in the years 2013 and 2015 for acetaminophen-opioid combination product exposures...
July 14, 2017: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
https://www.readbyqxmd.com/read/28702139/ramipril-associated-cholestasis-in-the-setting-of-recurrent-drug-induced-liver-injury
#8
David Forner, Tasha Kulai, Thomas Arnason, Steven E Gruchy, Magnus MacLeod
Aim: Angiotensin-converting enzyme inhibitors (ACEIs) are commonly used to treat hypertension. Although generally well tolerated, the adverse effects of ACEIs include hypotension, cough, acute kidney injury and hyperkalemia. Rare reports of ACEI-induced hepatotoxicity have been described, most notably a cholestatic pattern of injury related to captopril. A 67-year-old male presented to the emergency department with a three-week history of jaundice, pruritis and weakness. Eight weeks before, he began taking ramipril and clopidogrel...
2017: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/28701180/influence-of-genetic-variants-on-toxicity-to-anti-tubercular-agents-a-systematic-review-and-meta-analysis-protocol
#9
Marty Richardson, Jamie Kirkham, Kerry Dwan, Derek Sloan, Geraint Davies, Andrea Jorgensen
BACKGROUND: Tuberculosis patients receiving anti-tuberculosis treatment may experience serious adverse drug reactions, such as hepatotoxicity. Genetic risk factors, such as polymorphisms of the NAT2, CYP2E1 and GSTM1 genes, may increase the risk of experiencing such toxicity events. Many pharmacogenetic studies have investigated the association between genetic variants and anti-tuberculosis drug-related toxicity events, and several meta-analyses have synthesised data from these studies, although conclusions from these meta-analyses are conflicting...
July 13, 2017: Systematic Reviews
https://www.readbyqxmd.com/read/28700530/retrospective-study-of-patients-on-etanercept-therapy-for-rheumatic-diseases-in-patients-with-chronic-hepatitis-c-virus
#10
Nisarg P Gandhi, Augustine M Manadan, Joel A Block
OBJECTIVE: Treatment of rheumatic diseases with concurrent hepatitis C virus (HCV) infection is a therapeutic challenge. Etanercept has no known hepatotoxicity; however there is a concern for worsening of HCV infection-related liver disease due to immunosuppressive action of the drug. Here, we retrospectively assessed the safety of etanercept in rheumatologic disease in patients with chronic HCV. METHODS: A retrospective review was conducted in patients with chronic HCV infection who received etanercept for diagnosis of rheumatoid arthritis and psoriatic arthritis...
July 11, 2017: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/28699506/natural-or-plant-products-for-the-treatment-of-neurological-disorders-current-knowledge
#11
Mohammad Khalid Parvez
In recent decades, complementary and alternative medicine (CAM) has become very popular in the treatment of several chronic diseases. Natural products as one of the CAM modalities offer potential opportunities to discover lead compounds for novel drug development. The use of CAM or natural products in the prevention of neurodegenerative diseases is comparatively a newer area. Natural therapeutics with anti-oxidative and anti-inflammatory salutations evidently plays a crucial role in protecting neurons. Of these, the most promising are caffeine, trigonelline, shogaol, curcumin, resveratrol, baicalein, wogonin, ginsenosides, tanshinones, withanolides, picrosides, parthenolide, cannabinoids, Devil's claw and white willow bark, including Chinese formulations Renshen Shouwu and Shengmai San...
July 10, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28699415/a-scalable-approach-for-the-generation-of-human-pluripotent-stem-cell-derived-hepatic-organoids-with-sensitive-hepatotoxicity-features
#12
Malte Sgodda, Zhen Dai, Robert Zweigerdt, Amar D Sharma, Michael Ott, Tobias Cantz
The quest for physiologically-active human hepatocyte-like cells for in vitro research and drug screening is high. The recent progress in the field of pluripotent stem cell (PSC) - derived hepatic cells within the last decade brings those cells closer to applications in translational medicine. However, the classical two-dimensional (2D) cell culture systems are of limited use, because relevant cell-cell interactions based on cell polarity, which is a major prerequisite for proper hepatic cell metabolisms, are not provided...
July 12, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28696419/associations-between-the-c677t-and-a1298c-polymorphisms-of-mthfr-and-the-toxicity-of-methotrexate-in-childhood-malignancies-a-meta-analysis
#13
C Zhu, Y W Liu, S Z Wang, X L Li, X L Nie, X T Yu, L B Zhao, X L Wang
As a common chemotherapy drug, methotrexate (MTX) has achieved remarkable clinical success. However, high inter-individual variability and unpredictable toxicity continue to challenge its use in clinical practices. Some studies suggest this variation is associated with a methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, but results remain unclear. In this meta-analysis, we include 14 studies that focus on MTHFR C677T and A1298C polymorphisms in pediatric patients with malignancy. We found significant associations of the MTHFR C677T polymorphism with hepatotoxicity (grade ⩾2; CC vs CT/TT: risk ratio (RR): 0...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28691103/role-of-nonalcoholic-fatty-liver-disease-as-risk-factor-for-drug-induced-hepatotoxicity
#14
Julie Massart, Karima Begriche, Caroline Moreau, Bernard Fromenty
BACKGROUND: Obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions including fatty liver, nonalcoholic steatohepatitis (NASH) and cirrhosis. Different investigations showed or suggested that obesity and NAFLD are able to increase the risk of hepatotoxicity of different drugs. Some of these drugs could induce more frequently an acute hepatitis in obese individuals whereas others could worsen pre-existing NAFLD. AIM: The main objective of the present review was to collect the available information regarding the role of NAFLD as risk factor for drug-induced hepatotoxicity...
February 2017: Journal of Clinical and Translational Research
https://www.readbyqxmd.com/read/28689766/acute-administration-of-tramadol-and-tapentadol-at-effective-analgesic-and-maximum-tolerated-doses-causes-hepato-and-nephrotoxic-effects-in-wistar-rats
#15
Joana Barbosa, Juliana Faria, Sandra Leal, Luís Pedro Afonso, João Lobo, Odília Queirós, Roxana Moreira, Félix Carvalho, Ricardo Jorge Dinis-Oliveira
Tramadol and tapentadol are two atypical synthetic opioid analgesics, with monoamine reuptake inhibition properties. Mainly aimed at the treatment of moderate to severe pain, these drugs are extensively prescribed for multiple clinical applications. Along with the increase in their use, there has been an increment in their abuse, and consequently in the reported number of adverse reactions and intoxications. However, little is known about their mechanisms of toxicity. In this study, we have analyzed the in vivo toxicological effects in liver and kidney resulting from an acute exposure of a rodent animal model to both opioids...
July 6, 2017: Toxicology
https://www.readbyqxmd.com/read/28689274/impact-of-glutathione-transferases-genes-polymorphisms-in-nevirapine-adverse-reactions-a-possible-role-for-gstm1-in-sjs-ten-susceptibility
#16
Cinzia Ciccacci, Andrea Latini, Cristina Politi, Sandro Mancinelli, Maria C Marazzi, Giuseppe Novelli, Leonardo Palombi, Paola Borgiani
PURPOSE: Nevirapine (NVP) is used in developing countries as first-line treatment of HIV infection. Unfortunately, its use is associated with common serious adverse drug reactions, such as liver toxicity and the most severe and rare Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). GSTT1 and GSTM1 genes code for enzymes involved in the metabolism of a wide range of drugs. We hypothesized that this gene variability could be implicated in NVP adverse reactions. METHODS: We analyzed the GSTM1 and GSTT1 null genotypes by multiplex PCR in a population of 181 patients from Mozambique, treated with NVP...
July 8, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28687704/synergistic-cytotoxicity-from-drugs-and-cytokines-in-vitro-as-an-approach-to-classify-drugs-according-to-their-potential-to-cause-idiosyncratic-hepatotoxicity-a-proof-of-concept-study
#17
Ashley R Maiuri, Bronlyn Wassink, Jonathan D Turkus, Anna B Breier, Theresa Lansdell, Gurpreet Kaur, Sarah L Hession, Patricia E Ganey, Robert A Roth
Idiosyncratic, drug-induced liver injury (IDILI) typically occurs in a small fraction of patients and has resulted in removal of otherwise efficacious drugs from the market. Current preclinical testing methods are ineffective in predicting which drug candidates have IDILI liability. Recent results suggest that immune mediators such as tumor necrosis factor-alpha (TNF) and interferon-gamma (IFN) interact with drugs that cause IDILI to kill hepatocytes. This proof-of-concept study was designed to test the hypothesis that drugs can be classified according to their ability to cause IDILI in humans using logistic regression modeling with covariates derived from concentration-response relationships that describe cytotoxic interaction with cytokines...
July 7, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28685675/the-beneficial-effects-of-sulfur-containing-amino-acids-on-cisplatin-induced-cardiotoxicity-and-neurotoxicity-in-rodents
#18
Gvozden Rosic, Jovana Joksimovic, Dragica Selakovic, Vladimir Jakovljevic, Vladimir Zivkovic, Ivan Srejovic, Marko Djuric, Dragan Djuric
Cisplatin is one the most frequently used chemotherapeutic drugs for several decades. Although its antineoplastic effect has been reported in treatment of numerous malignances, various adverse effects seem to be the crucial limiting factor for its administration. Beside the most commonly described nephro- and hepatotoxicity, cisplatin therapy is also accompanied with gastrointestinal, reproductive, hematological, cardiovascular and neurological side effects. Since it has been reported that cisplatin induce oxidative damage in various tissues (by means of altered ROS production, as well as by depletion of antioxidants), it seems reasonable that huge efforts had been put in the investigations of antioxidant supplementation as potential therapeutical approach for attenuation of cisplatin toxicities...
July 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28685299/conjugated-and-entrapped-hpma-pla-nano-polymeric-micelles-based-dual-delivery-of-first-line-anti-tb-drugs-improved-and-safe-drug-delivery-against-sensitive-and-resistant-mycobacterium-tuberculosis
#19
Seema Upadhyay, Iliyas Khan, Avinash Gothwal, Praveen K Pachouri, N Bhaskar, Umesh D Gupta, Devendra S Chauhan, Umesh Gupta
PURPOSE: First line antiTB drugs have several physical and toxic manifestations which limit their applications. RIF is a hydrophobic drug and has low water solubility and INH is hepatotoxic. The main objective of the study was to synthesize, characterize HPMA-PLA co-polymeric micelles for the effective dual delivery of INH and RIF. METHODS: HPMA-PLA co-polymer and HPMA-PLA-INH (HPI) conjugates were synthesized and characterized by FT-IR and (1)H-NMR spectroscopy...
July 6, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28682524/restorative-effects-of-chrysin-pretreatment-on-oxidant-antioxidant-status-inflammatory-cytokine-production-and-apoptotic-and-autophagic-markers-in-acute-paracetamol-induced-hepatotoxicity-in-rats-an-experimental-and-biochemical-study
#20
Eyup Eldutar, Fatih Mehmet Kandemir, Sefa Kucukler, Cuneyt Caglayan
Paracetamol (PC) is a widely used analgesic and antipyretic drug, but it leads to acute hepatotoxicity at high doses intakes. This study was aimed to investigate the effects of Chrysin (CR) on hepatotoxicity constituted at high doses of PC in rats. Rats were subjected to oral pretreatment of CR (25 and 50 mg/kg b.w.) via feeding needle for 6 days against hepatotoxicity induced by a single dose of PC (500 mg/kg b.w.) administered orally via feeding needles. Although PC increases lipid peroxidation and liver enzyme activities, it has led to reduction of antioxidant enzyme activities...
July 6, 2017: Journal of Biochemical and Molecular Toxicology
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