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Basic & Clinical Pharmacology & Toxicology

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https://www.readbyqxmd.com/read/27911474/is-chelation-therapy-efficient-for-the-treatment-of-intravenous-metallic-mercury-intoxication
#1
Daniela Pelclova, Stepanka Vlckova, Ondrej Bezdicek, Manuela Vaneckova, Pavel Urban, Petr Ridzon, Pavel Diblik, Tomas Navratil, Pavlina Klusackova, Kamil Vlcek, Olga Benesova, Pavel Trestik, Jiri Homolka, Sergey Zakharov
The efficacy of treatment for intravenous elemental mercury intoxication has not been fully studied with regard to clinical outcomes, and treatment recommendations vary. We treated a 41-year-old man with a history of drug abuse and depression who attempted suicide using 1 mL (13.53 g) metallic Hg i.v. He was admitted to the hospital two months later for dyspnoea and thoracic pain and was diagnosed with pneumonia. Hg deposits were seen in the lungs and extra-pulmonary organs. His blood level (372 μg/L) exceeded the population level of 5 μg/L by more than 70-fold...
December 2, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27911044/utilization-of-stimulants-and-atomoxetine-for-attention-deficit-hyperactivity-disorder-among-5-4-million-children-using-population-based-longitudinal-data
#2
Kari Furu, Øystein Karlstad, Helga Zoega, Jaana E Martikainen, Shahram Bahmanyar, Helle Kieler, Anton Pottegård
Use of stimulants to treat Attention-deficit/hyperactivity disorder (ADHD) has increased over the past two decades and varies substantially between countries. The objective of this multinational population-based study was to examine utilization of ADHD drugs (stimulants and atomoxetine) including co-medication with other psychothropic drugs in the entire child population in the five Nordic countries. We included longitudinal data on dispensed ADHD drugs from five Nordic prescription registers during 2008-2012; which in 2012 comprised 48,296 individuals among 5...
December 2, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27901320/salivary-dna-methylation-profiling-aspects-to-consider-for-biomarker-identification
#3
Sabine A S Langie, Matthieu Moisse, Ken Declerck, Gudrun Koppen, Lode Godderis, Wim Vanden Berghe, Stacy Drury, Patrick De Boever
Is it not more comfortable to spit saliva in a tube than to be pricked with a needle to draw blood to analyse your health and disease risk? A lot of patients, study participants and (parents of) young children undoubtedly prefer non-invasive and convenient procedures. Such procedures increase compliance rates especially for longitudinal prospective studies. Saliva is an attractive biofluid providing good quality DNA to study epigenetic mechanisms underlying disease across development. In this MiniReview, we will describe the different applications of saliva in the field of epigenetics, focusing on genome-wide methylation analysis...
November 30, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27901310/topical-antimycotics-for-oral-candidiasis-in-warfarin-users
#4
Maja Hellfritzsch, Anton Pottegård, Andreas James Thestrup Pedersen, Alaa Burghle, Fatima Mouaanaki, Jesper Hallas, Erik Lerkevang Grove, Per Damkier
Treatment of oral candidiasis in warfarin users may be complicated by drug-drug interactions between warfarin and topically applied antimycotics. However, current knowledge of these putative drug-drug interactions is merely based on case series. We therefore performed a cohort cross-over study with the objective to evaluate the potential drug-drug interactions between warfarin and miconazole oral gel or nystatin oral solution. The cohort consisted of individuals using warfarin in the period of 1998-2012 (n≈7,400)...
November 30, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27893184/ecg-alterations-associated-with-psychotropic-drug-use-and-cacna1c-gene-variants-in-three-independent-samples
#5
Chiara Fabbri, Giuseppe Boriani, Igor Diemberger, Maria Giulia Filippi, Gloria Ravegnini, Patrizia Hrelia, Alessandro Minarini, Diego Albani, Gianluigi Forloni, Sabrina Angelini, Alessandro Serretti
Several antipsychotics and antidepressants have been associated with QTc prolongation or other ECG alterations, but their impact is still debated and other risk factors are known to affect QTc. We investigated the effect of antidepressants and antipsychotics on QTc and other ECG intervals/waves in three samples. Two discovery samples (cross-sectional sample n=145 and prospective sample n=68, naturalistic treatment) and a replication prospective sample (CATIE, n=515, randomized treatment) were analysed. In both prospective samples, baseline/follow-up changes in ECG parameters were analysed in relation to the number of psychotropic drugs stratified according to their known cardiovascular risk...
November 28, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27889951/performance-of-the-high-dimensional-propensity-score-in-a-nordic-health-care-model
#6
Jesper Hallas, Anton Pottegård
The high-dimensional propensity score (hdPS) is increasingly used as a tool to adjust for confounding in observational studies of drug effects. It was developed within very rich data sources, e.g., the American claims databases. Thus, it is unknown whether it can be applied in settings that provide little more than prescriptions and diagnoses from hospital contacts, as in the Nordic data sources. Our objective was to evaluate the performance of hdPS under such circumstances. As our model, we chose the association between use of selective cyclooxygenase-2 inhibitors (coxibs) and traditional NSAIDs (tNSAIDs) and the risk of upper GI bleeding...
November 27, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27889941/an-adductomic-approach-to-identify-electrophiles-in-vivo
#7
Henrik Carlsson, Margareta Törnqvist
Humans are exposed to many reactive electrophiles, both formed endogenously and from exogenous exposures. Such compounds could react with cellular biomolecules and form stable reaction products, adducts, at nucleophilic sites in proteins and DNA, constituting a risk for toxic effects. Adductomic approaches aim to study the totality of adducts, to specific biomolecules, by mass spectrometric screening. This MiniReview focuses on the development and application of an adductomic approach for the screening of unknown adducts to N-terminal valine (Val) in hemoglobin (Hb) by liquid chromatography tandem mass spectrometry (LC-MS/MS)...
November 27, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27888584/small-molecule-inhibiting-nf-kb-ameliorates-oxidative-stress-and-suppresses-renal-inflammation-in-early-stage-of-alloxan-induced-diabetic-nephropathy-in-rat
#8
Manash P Borgohain, Mangala Lakhar, Sahabuddin Ahmed, Liakat Chowdhury, Saurabh Kumar, Rajat Pant, Abhinav Choubey
Diabetic nephropathy is one of the major microvascular complications of diabetes mellitus which ultimately gives rise to cardiovascular diseases. Oxidative stress produced by prolonged hyperglycaemia and chronic renal inflammation are the two key players in the development and progression of diabetic nephropathy. NF-kB-mediated inflammatory cascade is a strong contributor to the renovascular inflammation in diabetic nephropathy. Here, we studied the effects of piceatannol, a potent NF-kB inhibitor, on various oxidative stress markers and diabetic renal inflammatory pathway in rat induced by alloxan...
November 26, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27888581/vascular-toxicity-risk-assessment-of-mc18-and-mc70-novel-potential-diagnostic-tools-for-in-vivo-pet-studies
#9
Fabio Fusi, Miriam Durante, Claudia Sticozzi, Maria Frosini, Maria G Perrone, Nicola A Colabufo, Simona Saponara
The P-glicoprotein (P-gp) inhibitor MC18 has been recently proposed as a valuable PET tracer to measure P-gp expression in vivo. The aim of this study was to evaluate the toxic hazard towards the vasculature of MC18 along with the structurally related and more potent P-gp inhibitor MC70. Their effects on A7r5 and EA.hy926 cells viability, on the mechanical activity of fresh and cultured rat aorta rings as well as on Cav 1.2 channel current (ICa1.2 ) of A7r5 cells were studied. At concentrations >10 μM, MC18 and MC70 decreased cell viability causing evident morphological changes...
November 26, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27888572/adverse-effect-profile-of-topical-ocular-administration-of-fingolimod-for-treatment-of-dry-eye-disease
#10
Weibao Xiao, Li Sun, Nan Zhang, Wen Ye
Fingolimod is a promising prodrug in attenuating multiple sclerosis and prolonging survival of organ allograft, with many other protective effects. Its mechanism of action is related to the internalization of sphingosine 1-phosphate receptors (S1PRs). Our previous study indicated that fingolimod eyedrop was efficacious in inhibiting ocular inflammation in a dry eye disease (DED) model of Non-Obese Diabetic (NOD) mice. In the current study, we evaluated potential adverse effects of fingolimod eyedrop. Inbred 10-week-old BALB/C mice were randomly divided into four groups, fingolimod-treated groups at three different concentrations (0...
November 26, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27883283/usefulness-of-transthoracic-echocardiography-parameters-and-brain-natriuretic-peptide-as-mortality-predictors-in-hospitalized-acutely-poisoned-patients-a-prospective-observational-study
#11
Catalina Lionte, Victorita Sorodoc, Cristina Bologa, Cristina Tuchilus, Elisabeta Jaba
Acute poisonings represent a common cause of morbidity and mortality worldwide. The prognostic utility of the transthoracic echocardiography (TTE) parameters combined with brain natriuretic peptide (BNP) in acute poisoning with different xenobiotics, upon admission in the hospital was not evaluated. This prospective observational cohort study included 229 acutely poisoned non-diabetic adults, with a median age of 44 years (range 18-90 years), 50.7% women, with an in-hospital mortality rate of 8.7%. Univariate logistic regression analysis showed that age, the left ventricle kinetic abnormalities, the E wave deceleration time (EDT) and BNP correlated significantly with mortality in acutely poisoned patients...
November 24, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27883274/impact-of-the-chronic-omega-3-fatty-acids-supplementation-in-hemiparkinsonism-model-induced-by-6-hydroxydopamine-in-rats
#12
Alexandre Sales Barros, Rafael Yuri Gouveia Crispim, Juliana Cavalcante Uchoa, Ricardo Basto Souza, Jonatas Cavalcante Lemos, Gerardo Cristino Filho, Mirna Marques Bezerra, Thales Fontenele Moraes Pinheiro, Silvânia Maria Mendes de Vasconcelos, Danielle Silveira Macêdo, Glauce Socorro de Barros Viana, Lissiana Magna Vasconcelos Aguiar
Parkinson's disease (PD) is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra. The neuronal degeneration may result from the convergence of a number of different pathogenic factors, including apoptosis, excitotoxicity and oxidative stress. Many studies emphasize the importance of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in vital processes such as maintenance of the properties of cell membranes and the participation in signal transduction and biodynamic activity of neuronal membranes...
November 24, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27883270/pharmacovigilance-skills-knowledge-and-attitudes-in-our-future-doctors-a-nationwide-study-in-the-netherlands
#13
Tim Schutte, Jelle Tichelaar, Michael O Reumerman, Rike van Eekeren, Robert Rissmann, Cornelis Kramers, Milan C Richir, Eugène P van Puijenbroek, Michiel A van Agtmael
Pharmacovigilance centres monitor the safety of drugs, based on adverse drug reactions (ADRs) reported by doctors, pharmacists and pharmaceutical companies. However, the underreporting of ADRs remains a major problem. Our aim was to investigate preparedness of future doctors for their role in pharmacovigilance, by assessing their pharmacovigilance awareness, skills and knowledge. The study was a nationwide e-survey among medical students (third to sixth year) of all eight medical schools in the Netherlands...
November 24, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27883269/oil-fortified-maize-porridge-increases-absorption-of-lumefantrine-in-children-with-uncomplicated-falciparum-malaria
#14
Norah Mwebaza, Markus Jerling, Lars L Gustafsson, Antero V Silva, Anton Pohanka, Celestino Obua, Paul Waako, Olof Beck, Manijeh Vafa Homann, Anna Färnert, Urban Hellgren
Artemether-lumefantrine (AL) is a first-line treatment for uncomplicated malaria. Absorption of lumefantrine (LUM) is fat-dependent, and in children intake is recommended with milk. We investigated whether oil-fortified maize porridge can be an alternative when milk is not available. In an open-label pharmacokinetic study, Ugandan children <5 years with uncomplicated Plasmodiun falciparum malaria were randomized to receive standard 6-dose AL treatment (1 tablet {20mgA/ 120mg LUM} if <15kg and 2 tablets if > 15 kg) with milk (A) or maize porridge plus oil (B)...
November 24, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27875029/decreased-activity-and-genetic-polymorphisms-of-cyp2c19-in-beh%C3%A3-et-s-disease
#15
Mustafa Tugrul Goktas, R Ozgur Karaca, Said Kalkisim, Lokman Cevik, Levent Kilic, Ali Akdogan, Melih O Babaoglu, Atilla Bozkurt, Leif Bertilsson, Umit Yasar
Behçet's disease (BD) is a systemic autoimmune disorder. Cytochrome P450 enzymes (CYPs) are responsible for various drug metabolism reactions as well as those of endogenous substances which may be associated with autoimmune disease susceptibility. Recently, we reported that in patients with BD, CYP2C9 seems to be down-regulated due to inflammation. In the same Turkish BD patients, we investigated whether also CYP2C19 activity is decreased. Lansoprazole (30 mg) was given as a probe drug to evaluate CYP2C19 activity in 59 patients with BD and 27 healthy control volunteers...
November 22, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27860286/trends-in-off-label-prescribing-of-sedatives-hypnotics-and-antidepressants-among-children-and-adolescents-a-danish-nationwide-register-based-study
#16
Eva Skovslund Nielsen, Lotte Rasmussen, Maja Hellfritzsch Poulsen, Per Hove Thomsen, Mette Nørgaard, Torben Laursen
In recent years, psychotropic drug use among children and adolescents in Europe and USA has increased. However, the majority of psychotropic drugs are not formally approved for use in children and adolescents, and consequently, use is often off-label. The objectives were to describe time trends in off-label prescribing rates and the most commonly used types of psychotropic drugs by age and gender in Danish children and adolescents. Using the Register of Medicinal Product Statistics, we identified all prescriptions for sedatives, hypnotics and antidepressants filled for children and adolescents in 2006-2012...
November 17, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27865054/biodistribution-of-carbon-nanotubes-in-animal-models
#17
Nicklas Raun Jacobsen, Peter Møller, Per Axel Clausen, Anne Thoustrup Saber, Christian Micheletti, Keld Alstrup Jensen, Håkan Wallin, Ulla Vogel
The many physical and chemical properties of carbon nanotubes (CNT) make it one of the most commercially attractive materials in the era of nanotechnology. Here, we review the recent publications on in vivo biodistribution of pristine and functionalized forms of single-walled and multi-walled CNT. Pristine CNT remains in the lung for months or even years following pulmonary deposition. If cleared, the majority of CNT move to the gastrointestinal (GI) tract via the mucociliary escalator. However, there appears to be no uptake of CNT from the GI tract, with a possible exception of the smallest functionalized SWCNT...
November 16, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27863000/activated-charcoal-hemoperfusion-in-the-treatment-of-experimental-amitriptyline-poisoning-in-pigs-the-effect-on-amitriptyline-plasma-concentration-and-hemodynamic-parameters
#18
Tejs Jansen, Henrik Petersen, Cecilie M Malskaer, Charlotte Gabel-Jensen, Kim Dalhoff, Thomas Eriksen, Bo Belhage, Lotte C G Hoegberg
Coated activated charcoal hemoperfusion (CAC-HP) is a well-known treatment modality. Case reports have revealed conflicting results about the efficacy of CAC-HP in the treatment of amitriptyline (AT) poisoning, and no randomised clinical trials have been identified in the literature. This study aimed at quantifying the efficacy of modern CAC-HP as an adjunctive treatment of AT intoxication compared to standard care alone. Fourteen female Danish landrace pigs were randomized to either standard care or standard care plus 4 hr of CAC-HP...
November 14, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27862978/abcc3-polymorphisms-and-mrna-expression-influence-the-concentration-of-a-carboxylic-acid-metabolite-in-patients-on-clopidogrel-and-aspirin-therapy
#19
André Ducati Luchessi, Marta Concheiro, Juliana de Freitas Germano, Vivian Nogueira Silbiger, Raul Hernandes Bortolin, Angelines Cruz, Oscar Quintela, Maria Brion, Angel Carracedo, Andres Iñiguez, Marisol Bravo, Manuel López-Rivadulla, Rosario Dominguez Crespo Hirata, Amanda Guerra Moraes Rego Sousa, Mario Hiroyuki Hirata
Acetylsalicylic acid and clopidogrel combined therapy has been reported to be beneficial in patients with acute coronary syndrome (ACS). Antiplatelet drug resistance, especially to clopidogrel, is a multifactorial phenomenon that affects a large number of ACS patients. The genetic contribution to this drug response is not fully elucidated. We investigated the relationship of ABC-type efflux subfamily C member 3 (ABCC3) polymorphisms and mRNA expression with plasma concentrations of clopidogrel, salicylic acid (SA), and a carboxylic acid metabolite (CAM)...
November 12, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27862994/colchicine-increases-ventricular-vulnerability-in-an-experimental-whole-heart-model
#20
Gerrit Frommeyer, Julius Krawczyk, Dirk G Dechering, Simon Kochhäuser, Patrick Leitz, Michael Fehr, Lars Eckardt
The traditional gout medication colchicine has been reported to effectively prevent atrial fibrillation recurrence after atrial fibrillation ablation or cardiac surgery in a few clinical trials. Severe adverse events have not yet been reported. The aim of the present study was to assess possible direct electrophysiological effects in an experimental whole-heart model. Ten rabbit hearts were isolated and Langendorff-perfused. Thereafter, colchicine was administered in 2 concentrations (1μM and 3μM). Eight endo- and epicardial monophasic action potentials and a 12-lead ECG showed a stable QT interval and action potential duration during colchicine infusion...
November 11, 2016: Basic & Clinical Pharmacology & Toxicology
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