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Kalliopi Gerogianni, Aspasia Tsezou, Konstantinos Dimas
Adverse drug reactions (ADRs) affect many patients and remain a major public health problem, as they are a common cause of morbidity and mortality. It is estimated that ADRs are responsible for about 6% of hospital admissions and about 9% of hospitalization costs. Skin is the organ that is most frequently involved in ADRs. Drug-induced skin injuries vary from mild maculopapular eruptions (MPE) to severe cutaneous adverse reactions (SCARs) that are potentially life threatening. Genetic factors have been suggested to contribute to these SCARs, and most significant genetic associations have been identified in the major histocompatibility complex (MHC) genes...
March 21, 2018: Molecular Diagnosis & Therapy
Beverley Kok, Erica L W Lester, William M Lee, A James Hanje, R Todd Stravitz, Safwat Girgis, Vaishali Patel, Joshua R Peck, Christopher Esber, Constantine J Karvellas
BACKGROUND: Tumor necrosis factor-α antagonists (anti-TNF-α) have been associated with drug-induced liver injury. However, cases of anti-TNF-α-associated acute liver failure have only been rarely reported. AIMS: To identify cases of anti-TNF-α-associated acute liver failure and evaluate patterns of liver injury and common characteristics to the cases. METHODS: The United States Acute Liver Failure Study Group database was searched from 1998 to 2014...
March 21, 2018: Digestive Diseases and Sciences
Gilda Varricchi, Pietro Ameri, Christian Cadeddu, Alessandra Ghigo, Rosalinda Madonna, Giancarlo Marone, Valentina Mercurio, Ines Monte, Giuseppina Novo, Paolo Parrella, Flora Pirozzi, Antonio Pecoraro, Paolo Spallarossa, Concetta Zito, Giuseppe Mercuro, Pasquale Pagliaro, Carlo G Tocchetti
Antineoplastic drugs can be associated with several side effects, including cardiovascular toxicity (CTX). Biochemical studies have identified multiple mechanisms of CTX. Chemoterapeutic agents can alter redox homeostasis by increasing the production of reactive oxygen species (ROS) and reactive nitrogen species RNS. Cellular sources of ROS/RNS are cardiomyocytes, endothelial cells, stromal and inflammatory cells in the heart. Mitochondria, peroxisomes and other subcellular components are central hubs that control redox homeostasis...
2018: Frontiers in Physiology
Tao Yang, David F Meoli, Javid Moslehi, Dan M Roden
While inhibition of phosphoinositide 3-kinase (PI3K) is an emerging strategy in cancer therapy, we and others have reported that this action can also contribute to drug-induced Q-T prolongation and arrhythmias by increasing cardiac late sodium current (INaL). Previous studies in mice implicate the PI3K-α isoform as the major effector of the INaL action. Here, we have determined the effects of new anticancer drugs targeting specific PI3K isoforms on INaL and action potentials (APs) in mouse cardiomyocytes and CHO cells...
March 21, 2018: Journal of Pharmacology and Experimental Therapeutics
Yilmaz Bilgic, Cengiz Yilmaz, Yasir Furkan Cagin, Yahya Atayan, Nese Karadag, Murat Muhsin Muhip Harputluoglu
INTRODUCTION: Drug induced acute toxic hepatitis can be idiosyncratic. Albendazole, a widely used broad spectrum antiparasitic drug is generally accepted as a safe drug. It may cause asymptomatic transient liver enzyme abnormalities but acute toxic hepatitis is very rare. Case Report : Herein, we present the case of 47 year old woman with recurrent acute toxic hepatitis after a single intake of albendazole in 2010 and 2014. The patient was presented with symptoms and findings of anorexia, vomiting and jaundice...
April 2017: Acta Gastro-enterologica Belgica
Yohei Kubota, Toh Yoon Ezekiel Wong
When elderly patients are prescribed many different medications, the risk for developing serious adverse events should be kept in mind. One of these adverse events is agranulocytosis, which, although rare, can be life-threatening if left untreated. The majority of agranulocytosis cases are caused by drugs, including antibiotics. Here, we report a case of severe agranulocytosis in a 96-year-old woman following antibiotic therapy which was successfully managed using recombinant human granulocyte colony-stimulating factor (rhG-CSF) and the appropriate choice of antibiotics to treat her concomitant infection...
2018: Case Reports in Medicine
Joseph Scafidi, Jonathan Ritter, Brooke M Talbot, Jorge Edwards, Li-Jin Chew, Vittorio Gallo
Newly developed targeted anticancer drugs inhibit signaling pathways commonly altered in adult and pediatric cancers. However, as these pathways are also essential for normal brain development, concerns have emerged of neurologic sequelae resulting specifically from their application in pediatric cancers. The neural substrates and age dependency of these drug-induced effects in vivo are unknown, and their long-term behavioral consequences have not been characterized. This study defines the age-dependent cellular and behavioral effects of these drugs on normally developing brains and determines their reversibility with post-drug intervention...
March 20, 2018: Cancer Research
Emily S Mohn, Hua J Kern, Edward Saltzman, Susan H Mitmesser, Diane L McKay
The long-term use of prescription and over-the-counter drugs can induce subclinical and clinically relevant micronutrient deficiencies, which may develop gradually over months or even years. Given the large number of medications currently available, the number of research studies examining potential drug-nutrient interactions is quite limited. A comprehensive, updated review of the potential drug-nutrient interactions with chronic use of the most often prescribed medications for commonly diagnosed conditions among the general U...
March 20, 2018: Pharmaceutics
Jingtao Lu, Jianguo Li, Gabriel Helmlinger, Nidal Al-Huniti
Modeling the relationship between drug concentrations and heart rate corrected QT interval (QTc) change from baseline (C-∆QTc), based on Phase I single ascending dose (SAD) or multiple ascending dose (MAD) studies, has been proposed as an alternative to thorough QT studies (TQT), in assessing drug-induced QT prolongation risk. The present analysis used clinical SAD, MAD and TQT study data of an experimental compound, AZD5672, to evaluate the performance of: (i) three computational platforms (linear mixed-effects modeling implemented via PROC MIXED in SAS, as well as in R using LME4 package and linear quantile mixed models (LQMM) implemented via LQMM package; (ii) different model structures with and without treatment- or time-specific intercepts; and (iii) three methods for calculating the confidence interval (CI) of QTc prolongation (analytical and bootstrap methods with fixed or varied geometric mean concentrations)...
March 19, 2018: Journal of Pharmacokinetics and Pharmacodynamics
Vik Veer, Henry Zhang, Jolien Beyers, Olivier Vanderveken, Bhik Kotecha
PURPOSE: The purpose of this international survey is to ascertain the current practice of drug-induced sleep endoscopy (DISE) for patients with sleep-disordered breathing (SDB) by Otolaryngologists in the United Kingdom and Belgium. We compare the results with recommendations from the European Position Paper on drug-induced sleep endoscopy. METHODS: An online questionnaire was circulated to Consultant Otolaryngologists, independent practitioners, and trainees across the two countries...
March 19, 2018: European Archives of Oto-rhino-laryngology
Daiju Yamazaki, Takashi Kitaguchi, Masakazu Ishimura, Tomohiko Taniguchi, Atsuhiro Yamanishi, Daisuke Saji, Etsushi Takahashi, Masao Oguchi, Yuta Moriyama, Sanae Maeda, Kaori Miyamoto, Kaoru Morimura, Hiroki Ohnaka, Hiroyuki Tashibu, Yuko Sekino, Norimasa Miyamoto, Yasunari Kanda
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are expected to become a useful tool for proarrhythmia risk prediction in the non-clinical drug development phase. Several features including electrophysiological properties, ion channel expression profile and drug responses were investigated using commercially available hiPSC-CMs, such as iCell-CMs and Cor.4U-CMs. Although drug-induced arrhythmia has been extensively examined by microelectrode array (MEA) assays in iCell-CMs, it has not been fully understood an availability of Cor...
March 3, 2018: Journal of Pharmacological Sciences
B Sanader, R Grohmann, P Grötsch, T Schumann, S Toto, P Fernando, S Stübner
Drug reaction with eosinophilia and systemic symptoms (DRESS) is an infrequent, but severe, adverse drug-induced reaction which occurs due to massive T-cell stimulation resulting in cytotoxicity and eosinophil activation and recruitment. The incidence is 0.4 cases per 100, 0000 in the general population; the mortality rate is up to 10%. Therefore, we believe that recognizing this syndrome is of particular importance. The problem we notice is that DRESS is often seen and described in patients receiving rheumatologic or anticonvulsant drugs, but very rarely in psychiatric hospitals, where Clozapine is frequently used, and that is the importance of this paper...
March 19, 2018: Pharmacopsychiatry
Sahana Hadihalli Veeregowda, Jayakumar Jyothinagaram Krishnamurthy, Bhuvana Krishnaswamy, Sarala Narayana
Gynecomastia is benign enlargement of male breast, drug-induced gynecomastia accounts for about 25%. We are reporting a case of spironolactone-induced unilateral gynecomastia. A 52-year-old male patient receiving multiple antihypertensives including hydrochlorothiazide presented with muscle weakness and easy fatigability. Investigations revealed hypokalemia; he was advised to stop hydrochlorothiazide and consume potassium-rich diet; since he did not respond to this, spironolactone was added. The patient improved symptomatically but developed painful swelling of the right breast after 12 months of treatment which was suspected to be spironolactone-induced gynecomastia...
January 2018: International Journal of Applied and Basic Medical Research
Maxime Mallet, Nicolas Weiss, Dominique Thabut, Marika Rudler
Hyperammonemia plays a key role in the pathophysiology of hepatic encephalopathy (HE) and most HE treatments are ammonia-lowering drugs. However, the usefulness of measuring ammonemia in routine practice remains controversial and not recommended systematically even when neurological symptoms are present. First, ammonemia measurement should be carefully performed in order to avoid a falsely elevated result. When performed, a normal ammonemia in a cirrhotic patient with neurological symptoms should lead to reconsider the diagnosis of HE...
March 15, 2018: Clinics and Research in Hepatology and Gastroenterology
Li-Mei Qu, Shu-Hua Wang, Kun Yang, David R Brigstock, Li Sun, Run-Ping Gao
BACKGROUND: The diagnosis of drug-induced autoimmune hepatitis (DIAIH) and its differentiation from idiopathic autoimmune hepatitis (AIH) is challenging. This study aimed to differentiate DIAIH from AIH by comparing the biochemical changes, histological features, and frequencies of CD4+ Foxp3+ CD25+/- regulatory T cells (Tregs) in liver tissues or peripheral blood lymphocytes. METHODS: A total of 15 DIAIH patients and 24 AIH patients who underwent liver biopsies at initial presentation were enrolled in this study...
February 19, 2018: Hepatobiliary & Pancreatic Diseases International: HBPD INT
Xianxun Shi, Huiyuan Bai, Ming Zhao, Xiaorong Li, Xianchao Sun, Hongbo Jiang, Ailing Fu
Drug-induced liver injury shares a common feature of mitochondrial dysfunction. Mitochondrial therapy (mitotherapy), which replaces malfunctional mitochondria with functional exogenous mitochondria, may be a fundamental approach for treating drug-mediated hepatotoxicity. Here, we suggested that mitochondria isolated from human hepatoma cell could be used to treat acetaminophen (APAP)-induced liver injury in mice. When the mitochondria were added into the cell media, they could enter primarily cultured mouse hepatocyte...
March 2, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Xi Wu, Xue Xue, Lihui Wang, Wenjing Wang, Jian Han, Xiaoxue Sun, Haotian Zhang, Yueyang Liu, Xiaohang Che, Jingyu Yang, Chunfu Wu
Autophagy, a cellular survival mechanism, is thought to allow the recycling of cellular breakdown products when cancer cells are subjected to chemotherapy, thus decreasing drug-induced apoptosis. Disulfiram (DSF), a drug widely used to control alcoholism, possesses anticancer activity by inducing apoptosis in vitro and in vivo in a copper (Cu)-dependent manner. Our previous studies proved that DSF/Cu exerts increased anti-tumor effects on non-small cell lung cancer (NSCLC) xenograft models, and inhibits NSCLC recurrence driven by ALDH-positive cancer stem cells...
March 13, 2018: European Journal of Pharmacology
Lucia Romero, Jordi Cano, Julio Gomis-Tena, Beatriz Trenor, Ferran Sanz, Manuel Pastor, Javier Saiz
Drug-induced proarrhythmicity is a major concern for regulators and pharmaceutical companies. For novel drug candidates, the standard assessment involves the evaluation of the potassium hERG channels block and the in vivo prolongation of the QT interval. However, this method is known to be too restrictive and to stop the development of potentially valuable therapeutic drugs. The aim of this work is to create an in silico tool for early detection of drug-induced proarrhythmic risk. The system is based on simulations of how different compounds affect the action potential duration (APD) of isolated endocardial, midmyocardial, and epicardial cells as well as the QT prolongation in a virtual tissue...
March 16, 2018: Journal of Chemical Information and Modeling
C Lavanya, Manjunatha M Venkataswamy, M K Sibin, M M Srinivas Bharath, G K Chetan
Increased telomerase activity can be blocked by targeting the hTERT activity at both RNA and catalytic subunits. Various inhibitors had been used to regulate hTERT activity in glioblastoma cell lines and showed promising results. The present study hypothesized that the telomerase specific inhibitor BIBR1532 can effectively down-regulate the telomerase activity in LN18 glioblastoma cell line. LN18 glioblastoma cell line was treated with various concentrations of BIBR1532 at different time intervals. MTT assay was performed to determine cell viability after BIBR1532 treatment...
March 15, 2018: Cytotechnology
Barbara Wiśniowska, Sebastian Polak
The current study is an example of drug-disease interaction modeling where a drug induces a condition which can affect the pharmacodynamics of other concomitantly taken drugs. The electrophysiological effects of hypokaliemia and heart rate changes induced by the antiasthmatic drugs were simulated with the use of the cardiac safety simulator. Biophysically detailed model of the human cardiac physiology-ten Tusscher ventricular cardiomyocyte cell model-was employed to generate pseudo-ECG signals and QTc intervals for 44 patients from four clinical studies...
March 15, 2018: Journal of Pharmacokinetics and Pharmacodynamics
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