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https://www.readbyqxmd.com/read/28433619/lack-of-pathogenic-mutations-in-sos1-gene-in-phenytoin-induced-gingival-overgrowth-patients
#1
Katia Margiotti, Giulia Pascolini, Federica Consoli, Valentina Guida, Carlo Di Bonaventura, Anna Teresa Giallonardo, Antonio Pizzuti, Alessandro De Luca
OBJECTIVE: Gingival overgrowth is a side effect associated with some distinct classes of drugs, such as anticonvulsants, immunosuppressants, and calcium channel blockers. One of the main drugs associated with gingival overgrowth is the antiepileptic phenytoin, which affects gingival tissues by altering extracellular matrix metabolism. It has been shown that mutation of human SOS1 gene is responsible for a rare hereditary gingival fibromatosis type 1, a benign gingival overgrowth. The aim of the present study is to evaluate the possible contribution of SOS1 mutation to gingival overgrowth-related phenotype...
April 5, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28432048/solithromycin-a-novel-ketolide-antibiotic
#2
Michael J Buege, Jack E Brown, Samuel L Aitken
PURPOSE: The pharmacology, pharmacokinetics, pharmacodynamics, antimicrobial activity, clinical safety, and current regulatory status of solithromycin are reviewed. SUMMARY: Solithromycin is a novel ketolide antibiotic developed for the treatment of community-acquired bacterial pneumonia (CABP). Its pharmacologic, pharmacokinetic, and pharmacodynamic properties provide activity against a broad range of intracellular organisms, including retained activity against pathogens displaying various mechanisms of macrolide resistance...
April 21, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28432009/the-lateral-hypothalamus-to-lateral-habenula-projection-but-not-the-ventral-pallidum-to-lateral-habenula-projection-regulates-voluntary-ethanol-consumption
#3
Chandni Sheth, Teri M Furlong, Kristen A Keefe, Sharif A Taha
The lateral habenula (LHb) is an epithalamic brain region implicated in aversive processing via negative modulation of midbrain dopamine (DA) and serotonin (5-HT) systems. Given the role of the LHb in inhibiting DA and 5-HT systems, it is thought to be involved in various psychiatric pathologies, including drug addiction. In support, it has been shown that LHb plays a critical role in cocaine- and ethanol-related behaviors, most likely by mediating drug-induced aversive conditioning. In our previous work, we showed that LHb lesions increased voluntary ethanol consumption and operant ethanol self-administration and blocked yohimbine-induced reinstatement of ethanol self-administration...
April 18, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28429935/saponins-ginsenosides-from-the-leaves-of-panax-quinquefolius-ameliorated-acetaminophen-induced-hepatotoxicity-in-mice
#4
Xingyue Xu, Junnan Hu, Zhi Liu, Rui Zhang, Yufang He, Wei Hou, Zhiqing Wang, Ge Yang, Wei Li
Acetaminophen (APAP) overdose is the most frequent inducement of drug-induced acute liver injury (ALI). The purpose of this study was to investigate the protective effect of saponins (ginsenosides) from the leaves of Panax quinquefolius (PQS) against APAP-induced hepatotoxicity and the involved mechanism were investigated. Mice were pretreated with PQS (150 and 300 mg/kg) by oral gavage for seven days before being treated with 250 mg/kg APAP. Sever liver injury was exerted at 24 h post-APAP and hepatotoxicity was assessed...
April 21, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28429680/the-inhibitory-effects-of-hydamtiq-a-novel-parp-inhibitor-on-growth-in-human-tumor-cell-lines-with-defective-dna-damage-response-pathways
#5
Enrico Mini, Ida Landini, Laura Lucarini, Andrea Lapucci, Cristina Napoli, Gabriele Perrone, Renato Tassi, Emanuela Masini, Flavio Moroni, Stefania Nobili
The poly(ADP-ribose) polymerase (PARP) enzymes play key roles in the regulation of cellular processes (e.g. DNA damagerepair, genomic stability). It has been shown that PARP inhibitors (PARPIs) are selectively cytotoxic against cells with dysfunctions in genes involved in DNA repair mechanisms (synthetic lethality). Drug induced PARP inhibition potentiates the activity of anticancer drugs such as 5-fluorouracil in enhancing DNA damage, whose repair involves PARP1 activity.The aim of this study was to evaluate the growth inhibitory effects of a novel PARPI, HYDAMTIQ, on human tumor cell lines characterized by different features with regard to DNA damage response pathways (BRCA mutational status, microsatellite status and ATM expression level) and degree of sensitivity/resistance to 5-fluorouracil...
April 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28429460/automated-t-wave-analysis-can-differentiate-acquired-qt-prolongation-from-congenital-long-qt-syndrome
#6
Alan Sugrue, Peter A Noseworthy, Vaclav Kremen, J Martijn Bos, Bo Qiang, Ram K Rohatgi, Yehu Sapir, Zachi I Attia, Peter Brady, Pedro J Caraballo, Samuel J Asirvatham, Paul A Friedman, Michael J Ackerman
BACKGROUND: Prolongation of the QT on the surface electrocardiogram can be due to either genetic or acquired causes. Distinguishing congenital long QT syndrome (LQTS) from acquired QT prolongation has important prognostic and management implications. We aimed to investigate if quantitative T-wave analysis could provide a tool for the physician to differentiate between congenital and acquired QT prolongation. METHODS: Patients were identified through an institution-wide computer-based QT screening system which alerts the physician if the QTc ≥ 500 ms...
April 21, 2017: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/28429292/preparation-of-chloramphenicol-amino-acid-combinations-exhibiting-enhanced-dissolution-rates-and-reduced-drug-induced-oxidative-stress
#7
Vanesa B Sterren, Virginia Aiassa, Claudia Garnero, Yamila Garro Linck, Ana K Chattah, Gustavo A Monti, Marcela R Longhi, Ariana Zoppi
Chloramphenicol is an old antibiotic agent that is re-emerging as a valuable alternative for the treatment of multidrug-resistant pathogens. However, it exhibits suboptimal biopharmaceutical properties and toxicity profiles. In this work, chloramphenicol was combined with essential amino acids (arginine, cysteine, glycine, and leucine) with the aim of improving its dissolution rate and reduce its toxicity towards leukocytes. The chloramphenicol/amino acid solid samples were prepared by freeze-drying method and characterized in the solid state by using Fourier transform infrared spectroscopy, powder X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and solid-state nuclear magnetic resonance...
April 20, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28429185/high-content-assessment-of-cardiac-function-using-heart-on-a-chip-devices-as-drug-screening-model
#8
Genevieve Conant, Benjamin Fook Lun Lai, Rick Xing Ze Lu, Anastasia Korolj, Erika Yan Wang, Milica Radisic
Drug discovery and development continues to be a challenge to the pharmaceutical industry despite great advances in cell and molecular biology that allow for the design of better targeted therapeutics. Many potential drug compounds fail during the clinical trial due to inefficacy and toxicity that were not predicted during preclinical stages. The fundamental problem lies with the use of traditional drug screening models that still largely rely on the use of cell lines or animal cell monolayers, which leads to lack of predictive power of human tissue and organ response to the drug candidates...
April 20, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28428532/ceftriaxone-induced-hemolytic-anemia-in-a-jehovah-s-witness
#9
James Tasch, Pedro Gonzalez-Zayaz
BACKGROUND Drug-induced immune hemolytic anemia (DIIHA) is a rare condition that may result from the administration of an antibiotic, most notably the cephalosporin class, commonly used in both the adult and pediatric populations. A delay in recognition by a provider may lead to continuation of the offending agent and possibly result in fatal outcomes. CASE REPORT We report the case of a 65-year-old woman on ceftriaxone infusions after being diagnosed with acute mitral valve endocarditis 3 weeks prior, which presented with severe anemia and bilateral transient vision loss...
April 21, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28428443/mechanisms-of-pinometostat-epz-5676-treatment-emergent-resistance-in-mll-rearranged-leukemia
#10
Carly T Campbell, Jessica N Haladyna, David A Drubin, Ty M Thomson, Michael J Maria, Taylor Yamauchi, Nigel J Waters, Edward J Olhava, Roy M Pollock, Jesse J Smith, Robert A Copeland, Stephen J Blakemore, Kathrin M Bernt, Scott R Daigle
DOT1L is a protein methyltransferase involved in the development and maintenance of MLL-rearranged (MLL-r) leukemia through its ectopic methylation of histones associated with well characterized leukemic genes.  Pinometostat (EPZ-5676), a selective inhibitor of DOT1L, is in clinical development in relapsed/refractory acute leukemia patients harboring rearrangements of the MLL gene. The observation of responses and subsequent relapses in the adult trial treating MLL-r patients motivated preclinical investigations into potential mechanisms of pinometostat treatment emergent resistance (TER) in cell lines confirmed to have MLL-r...
April 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28428362/hepatic-lipid-accumulation-cause-and-consequence-of-dysregulated-glucoregulatory-hormones
#11
Caroline E Geisler, Benjamin Jennings Renquist
Fatty liver can be diet, endocrine, genetic, viral, or drug induced. Independent of cause, hepatic lipid accumulation promotes systemic metabolic dysfunction. By acting as peroxisome proliferator activated receptor (PPAR) ligands, hepatic non-esterified fatty acids upregulate expression of gluconeogenic, beta-oxidative, lipogenic, and ketogenic genes, promoting hyperglycemia, hyperlipidemia, and ketosis. The typical hormonal environment in fatty liver disease consists of hyperinsulinemia, hyperglucagonemia, hypercortisolemia, growth hormone deficiency, and elevated sympathetic tone...
April 20, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28427045/mir-142-3p-overexpression-increases-chemo-sensitivity-of-nsclc-by-inhibiting-hmgb1-mediated-autophagy
#12
Yuqing Chen, Xin Zhou, Jianou Qiao, Aihua Bao
BACKGROUND: Non-small-cell lung cancer (NSCLC) is a deadly cancer with high mortality rate. Drug resistance represents a main obstacle in NSCLC treatment. High mobility group box-1 (HMGB1) protein promotes drug resistance in NSCLC cells by activating protective autophagy. METHODS: In the current study, we investigated the regulatory role of microRNA-142-3p (miR-142-3p) in HMGB1-mediated autophagy of NSCLC cells and its impact on drug resistance of NSCLC in vitro and in vivo...
March 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28425415/drug-induced-liver-injury-at-a-tertiary-hospital-in-india-etiology-clinical-features-and-predictors-of-mortality
#13
Chetan Rathi, Nirav Pipaliya, Ruchir Patel, Meghraj Ingle, Aniruddha Phadke, Prabha Sawant
INTRODUCTION AND AIMS: Drug-induced liver injury (DILI) is rare; however, it is one of the important causes of acute liver failure which results in significant morbidity or mortality. MATERIAL AND METHODS: Patients with suspected DILI were enrolled based on predefined criteria and followed up for at least 6 months or until normalization of liver tests. Causality assessment was done by applying the Roussel Uclaf Causality Assessment Method model. RESULTS: We collected data from 82 individuals diagnosed with DILI at our hospital from 2014 through 2015 (41 men; median age, 38 years)...
May 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28425222/class-iii-antiarrhythmic-drugs-amiodarone-and-dronedarone-impair-kir-2-1-backward-trafficking
#14
Yuan Ji, Hiroki Takanari, Muge Qile, Lukas Nalos, Marien J C Houtman, Fee L Romunde, Raimond Heukers, Paul M P van Bergen En Henegouwen, Marc A Vos, Marcel A G van der Heyden
Drug-induced ion channel trafficking disturbance can cause cardiac arrhythmias. The subcellular level at which drugs interfere in trafficking pathways is largely unknown. KIR 2.1 inward rectifier channels, largely responsible for the cardiac inward rectifier current (IK1 ), are degraded in lysosomes. Amiodarone and dronedarone are class III antiarrhythmics. Chronic use of amiodarone, and to a lesser extent dronedarone, causes serious adverse effects to several organs and tissue types, including the heart. Both drugs have been described to interfere in the late-endosome/lysosome system...
April 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28424016/acute-brain-injury-following-illicit-drug-abuse-in-adolescent-and-young-adult-patients-spectrum-of-neuroimaging-findings
#15
Shai Shrot, Andrea Poretti, Elizabeth W Tucker, Bruno P Soares, Thierry Agm Huisman
The use of illicit drugs is currently a major medical problem among adolescents. Several illicit drugs have a high abuse potential and can be neurotoxic causing high morbidity and mortality. The clinical manifestation of adolescents with acute drug-induced neurotoxicity is often characterized by non-specific symptoms and findings. Early diagnosis is important to prevent death and permanent long-term neurological impairments. We report on clinical and neuroimaging findings in five adolescents with acute brain imaging following illicit drug intoxication to highlight the role of neuroimaging findings in the diagnostic work-up of pediatric acute drug-induced neurotoxicity...
April 2017: Neuroradiology Journal
https://www.readbyqxmd.com/read/28423573/involvement-of-af1q-mllt11-in-the-progression-of-ovarian-cancer
#16
Paola Tiberio, Ludmila Lozneanu, Valentina Angeloni, Elena Cavadini, Patrizia Pinciroli, Maurizio Callari, Maria Luisa Carcangiu, Domenica Lorusso, Francesco Raspagliesi, Valentina Pala, Maria Grazia Daidone, Valentina Appierto
The functional role of AF1q/MLLT11, an oncogenic factor involved in a translocation t(1;11)(q21;q23) responsible for acute myeloid leukaemia, has been investigated in hematological and solid malignancies and its expression was found to be linked to tumor progression and poor clinical outcome. In addition to its oncogenic function, AF1q has been shown to play a role in the onset of basal and drug-induced apoptosis in cancer cells of different histotypes, including ovarian cancer. Through in vitro, ex vivo, and in silico approaches, we demonstrated here that AF1q is also endowed with protumorigenic potential in ovarian cancer...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422076/zeglobaltox-an-innovative-approach-to-address-organ-drug-toxicity-using-zebrafish
#17
Carles Cornet, Simone Calzolari, Rafael Miñana-Prieto, Sylvia Dyballa, Els van Doornmalen, Helma Rutjes, Thierry Savy, Davide D'Amico, Javier Terriente
Toxicity is one of the major attrition causes during the drug development process. In that line, cardio-, neuro-, and hepatotoxicities are among the main reasons behind the retirement of drugs in clinical phases and post market withdrawal. Zebrafish exploitation in high-throughput drug screening is becoming an important tool to assess the toxicity and efficacy of novel drugs. This animal model has, from early developmental stages, fully functional organs from a physiological point of view. Thus, drug-induced organ-toxicity can be detected in larval stages, allowing a high predictive power on possible human drug-induced liabilities...
April 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28421966/regulatory-forum-review-utility-of-in-vitro-secondary-pharmacology-data-to-assess-risk-of-drug-induced-valvular-heart-disease-in-humans-regulatory-considerations
#18
Thomas Papoian, Gowraganahalli Jagadeesh, Muriel Saulnier, Natalie Simpson, Arippa Ravindran, Baichun Yang, Adebayo A Laniyonu, Imran Khan, Ana Szarfman
Drug-induced valvular heart disease (VHD) is a serious side effect linked to long-term treatment with 5-hydroxytryptamine (serotonin) receptor 2B (5-HT2B) agonists. Safety assessment for off-target pharmacodynamic activity is a common approach used to screen drugs for this undesired property. Such studies include in vitro assays to determine whether the drug is a 5-HT2B agonist, a necessary pharmacological property for development of VHD. Measures of in vitro binding affinity (IC50, Ki) or cellular functional activity (EC50) are often compared to maximum therapeutic free plasma drug levels ( fCmax) from which safety margins (SMs) can be derived...
April 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28421728/oral-pigmentations-in-physiologic-conditions-post-inflammatory-affections-and-systemic-diseases
#19
Martina Lambertini, Annalisa Patrizi, Giulia M Ravaioli, Emi Dika
Melanocytes are found throughout the oral mucosa but usually go unnoticed because of their relatively low level of pigment production. When focally or generally active in pigment production or proliferation they may be responsible for several affections in the oral mucosae ranging from physiologic pigmentation, systemic diseases to malignant neoplasms. The diagnosis of oral pigmentations (OP) is usually challenging for the physician, but a careful examination of the oral cavity may reveal the first manifestation of underlying systemic diseases...
April 19, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/28421296/metabolite-signatures-of-doxorubicin-induced-toxicity-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#20
Umesh Chaudhari, James K Ellis, Vilas Wagh, Harshal Nemade, Jürgen Hescheler, Hector C Keun, Agapios Sachinidis
Drug-induced off-target cardiotoxicity, particularly following anti-cancer therapy, is a major concern in new drug discovery and development. To ensure patient safety and efficient pharmaceutical drug development, there is an urgent need to develop more predictive cell model systems and distinct toxicity signatures. In this study, we applied our previously proposed repeated exposure toxicity methodology and performed (1)H NMR spectroscopy-based extracellular metabolic profiling in culture medium of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exposed to doxorubicin (DOX), an anti-cancer agent...
April 18, 2017: Amino Acids
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