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Basic & Clinical Pharmacology & Toxicology

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https://www.readbyqxmd.com/read/29334172/silica-nanoparticle-induced-cytokine-responses-in-beas-2b-and-hbec3-kt-cells-significance-of-particle-size-and-signalling-pathways-in-different-lung-cell-cultures
#1
Marit Låg, Tonje Skuland, Anna Godymchuk, Thu H T Nguyen, Hang L T Pham, Magne Refsnes
We have previously reported that silica nanoparticles (SiNPs) of nominal size 50 nm (Si50) induce the pro-inflammatory cytokines CXCL8 and IL-6 in BEAS-2B cells, via mechanisms involving MAPK p38, TACE-mediated TGFα release and the NFκB pathway. In the present study, we examined whether these findings are cell-specific or might be extended to another epithelial lung cell model, HBEC3-KT, and also to SiNPs of a smaller size (nominal size of 10 nm; Si10). The TEM average size of Si10 and Si50 was 10.9 nm and 34...
January 15, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29327815/no-impact-of-pre-existing-cardiovascular-disease-on-prescribing-patterns-of-sulphonylureas-in-denmark-a-registry-based-nationwide-study
#2
Malin Nilsson, Jørgen Rungby, Nathan Lassota, Andreas Daugaard Jørgensen, Rikke Ibsen, Jakob Kjellberg
Uncertainty exists regarding cardiovascular (CV) safety of sulphonylureas (SUs) as reflected in package labels and treatment guidelines. This study evaluated clinical treatment practice for SUs by analysing prescription patterns for SUs relative to patient history of CV disease (CVD). Patients in Denmark initiating treatment with SU or other anti-hyperglycaemic drugs during 2006-2012 were retrospectively identified using national health registries. Pre-existing (previous 12 years) overall CVD, coronary heart disease (CHD) and myocardial infarction (MI) were subsequently identified...
January 12, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29327809/the-prevalence-of-cannabinoid-hyperemesis-syndrome-among-regular-marijuana-smokers-in-an-urban-public-hospital
#3
Joseph Habboushe, Ada Rubin, Haoming Liu, Robert S Hoffman
Epidemiological data, including prevalence, for cannabinoid hyperemesis syndrome (CHS) remain largely unknown. Without these data, clinicians often describe CHS as "rare" or "very rare" without supporting information. We seek to estimate the prevalence of CHS in a population of patients presenting to a socioeconomically and racially diverse urban Emergency Department of a public hospital. This study consisted of a questionnaire administered to a convenience sample of patients presenting to the ED of the oldest public hospital in the United States...
January 12, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29327413/itpa-activity-in-children-treated-by-azathioprine-relationship-to-the-occurrence-of-adverse-drug-reactions-and-inflammatory-response
#4
Antony Citterio-Quentin, Mustapha Moulsma, Marie-Paule Gustin, Alain Lachaux, Roselyne Boulieu
Azathioprine (AZA), a thiopurine drug, is widely used in the treatment of children with immunological disease such as inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH); however, interindividual variability in the occurrence of adverse drug reaction (ADRs) and drug response is observed. This study investigated 1) the relationships between inosine triphosphate pyrophosphatase (ITPA) activity, an enzyme involved in thiopurine metabolism, and the occurrence of ADRs in children with immunological disease on AZA therapy, 2) the relationship between ITPA activity and the inflammatory activity observed in children with IBD...
January 11, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29325225/influence-of-cyp2d6-cyp3a4-cyp3a5-and-abcb1-polymorphisms-on-pharmacokinetics-and-safety-of-aripiprazole-in-healthy-volunteers
#5
Carmen Belmonte, Dolores Ochoa, Manuel Román, Miriam Saiz-Rodríguez, Aneta Wojnicz, Clara Isabel Gómez-Sánchez, Samuel Martín-Vilchez, Francisco Abad-Santos
The aim of this study was to investigate the effect of polymorphisms in cytochrome P450 (CYP) 2D6, CYP3A4 and CYP3A5 enzymes and in P-glycoprotein (P-gp) on the pharmacokinetics and safety of aripiprazole and, its active metabolite, dehydro-aripiprazole, in 148 healthy volunteers from 6 bioequivalence trials receiving a single oral dose of aripiprazole. The plasma concentrations of both analytes were measured by LC-MS/MS. CYP2D6 (*3,*4,*5,*6,*7,*9 and copy number variations), CYP3A4 (*20 and *22), CYP3A5*3 and C3435T, C1236T and G2677T/A in ABCB1 gene were determined...
January 11, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29319222/availability-of-paracetamol-sold-over-the-counter-in-europe-a-descriptive-cross-sectional-international-survey-of-pack-size-restriction
#6
Britt Reuter Morthorst, Annette Erlangsen, Merete Nordentoft, Keith Hawton, Lotte Christine Groth Hoegberg, Kim Peder Dalhoff
Due to the risk of hepatotoxicity when excessive amounts of paracetamol are consumed, Poisons Information Centers (PICs) frequently receive paracetamol-related enquiries. This study examined how widely pack size restrictions of paracetamol sold over-the-counter have been implemented in Europe and also availability of paracetamol through non-pharmacy outlets and their possible associations with frequency of poisoning enquiries. A cross-sectional European multicentre questionnaire study was performed using a questionnaire to identify the extent and nature of paracetamol pack size restrictions, non-pharmacy outlet sales and the frequency of paracetamol-related enquiries to PICs...
January 10, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29316278/integrated-approaches-to-testing-and-assessment-iata-oecd-activities-on-the-development-and-use-of-adverse-outcome-pathways-and-case-studies
#7
Yuki Sakuratani, Masashi Horie, Eeva Leinala
The Organisation for Economic Co-operation and Development (OECD) works with member countries and other stakeholders to improve and harmonise chemical assessment methods. In 2012, the OECD Adverse Outcome Pathways (AOPs) Development Programme started. The Programme has published six AOPs thus far and more than 60 AOPs are under various stages of development under the Programme. This paper reviews recent OECD activities on the use of AOPs in developing Integrated Approaches to Testing and Assessments (IATAs)...
January 9, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29316226/a-systematic-review-on-insulin-overdose-cases-clinical-course-complications-and-novel-treatment-options
#8
Nicklas Järvelä Johansen, Mikkel Bring Christensen
A large overdose of insulin is a serious health matter. Information concerning administration and duration of intravenous (IV) glucose, other treatment options or complications beside hypoglycaemia following large insulin overdoses is not readily apparent from the literature. This article is protected by copyright. All rights reserved.
January 9, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29316298/improving-the-safety-assessment-of-chemicals-and-drug-candidates-by-the-integration-of-bio-informatics-and-chemoinformatics-data
#9
Thomas Steger-Hartmann, Francois Pognan
The application of read-across and in silico tools for regulatory decision-making has been limited for pharmaceutical compounds to the assessment of genotoxic impurity. In contrast, the broad availability of toxicity data for industrial chemicals has triggered regulatory frameworks for read-across (e.g. ECHA read-across assessment framework), software tools and public databases for an automated process of gap filling for safety assessment framework. This MiniReview provides an overview of the currently existing in silico and read-across approaches for chemicals together with recent developments for pharmaceutical compounds in these areas...
January 7, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29285878/a-comparison-of-the-effectiveness-of-silibinin-and-resveratrol-in-preventing-alpha-amanitin-induced-hepatotoxicity
#10
Aynur Sahin, M Aylin Arici, Yeliz Yılmaz, Sule Kalkan, Nergiz Durmus, Bekir Ugur Ergur, İlkay Aksu, Neşe Atabey, Yesim Tuncok
Amanita phalloides species mushrooms containing alpha amanitin (α-AMA) are responsible for the majority of fatal mushroom intoxications and can lead to severe poisonings resulting in hepatotoxicity and acute hepatic failure. Existing antidotes, such as silibinin, are not sufficiently effective in the prevention and/or resolution of α-AMA-induced hepatotoxicity. We investigated the effects of resveratrol on α-AMA-induced hepatotoxicity and compared with silibinin, a known antidote using in vivo and in vitro toxicity models...
December 29, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29281181/the-cumulative-daily-tolerance-levels-of-potentially-toxic-excipients-ethanol-and-propylene-glycol-are-commonly-exceeded-in-neonates-and-infants
#11
K S Valeur, S A Hertel, K E Lundstrøm, H Holst
Poly-medicated neonates and young infants may be at risk of harmful cumulative exposure to toxic excipients like ethanol, propylene glycol and benzyl alcohol during routine clinical care. The aim of this study was to calculate the cumulative daily alcohol exposure (mg/kg/day) in poly-medicated neonates and infants and compare these levels to the tolerance limits found in guidelines published by European Medicines Agency (EMA). As part of the SEEN study, all medicinal products administered to neonates and infants were recorded...
December 27, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29278445/the-effect-of-7-hydroxycoumarin-on-dextran-sulfate-sodium-induced-ulcerative-colitis
#12
Chengzheng Wang, Jing Liu, Yingchun Zhou, Gao Feng
7-Hydroxycoumarin (HC) or Umbelliferone exerts many beneficial effects, ie. antioxidant, anti-tumour, anti-inflammatory and immunomodulatory activities. We hypothesized that HC had mitigating properties on ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice, via suppression of inflammation. The induction of UC in mice was achieved by the administration of 3.5% DSS in drinking water for 7 consecutive days. Administration of HC to DSS-induced mice ameliorated the loss of body weight, reduced diarrhoea and gross bleeding and showed a significant reduction in the disease activity index (DAI)...
December 26, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29278444/%C3%AE-adrenergic-receptor-blocker-ici-118-551-selectively-increases-intermediate-conductance-calcium-activated-potassium-channel-ikca-mediated-relaxations-in-rat-main-mesenteric-artery
#13
Melike Hacer Ozkan, Serdar Uma
Endothelial IKCa and/or SKCa channels play an important role in the control of vascular tone by participating in endothelium-dependent relaxation. Whether β-AR antagonists, mainly used in hypertension, affect endothelial KCa channel function is unknown. In this study, we examined the effect of the β2-AR antagonist and inverse agonist ICI 118,551 on the IKCa /SKCa channel activity by assessing functional relaxation responses to several agonists that stimulate these channels. Mesenteric arterial rings isolated from male Spraque-Dawley mounted to organ baths...
December 26, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29265740/considerations-for-pharmacoepidemiological-studies-of-drug-cancer-associations
#14
Anton Pottegård, Søren Friis, Til Stürmer, Jesper Hallas, Shahram Bahmanyar
In this MiniReview, we provide general considerations for the planning and conduct of pharmacoepidemiological studies of associations between drug use and cancer development. We address data sources, study design, assessment of drug exposure, ascertainment of cancer outcomes, confounder adjustment and future perspectives. Aspects of data sources include assessment of complete history of drug use and data on dose and duration of drug use, allowing estimates of cumulative exposure. Outcome data from formal cancer registries are preferable, but cancer data from other sources, e...
December 18, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29265731/disproportionality-analysis-used-to-identify-patterns-in-medication-error-reports-involving-hospitalized-children
#15
Rikke Mie Rishoej, Henrik Thybo Christesen, Lene Juel Kjeldsen, Anna Birna Almarsdóttir, Jesper Hallas
Medication errors (MEs) in children are frequent and associated with increased risk of harm (1,2). Incident reporting of errors is considered a key element in strategies to reduce MEs (3). Traditionally, analyses of ME reports involve narrative descriptions and frequency counts which may cause important errors to be overlooked or may entail an element of subjectivism (2,4). A formal approach to analysis of ME reports could involve disproportionality principles used in pharmacovigilance, for example the proportional reporting ratio (PRR) (5)...
December 18, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29235718/letter-from-the-editor
#16
LETTER
Kim Brøsen
No abstract text is available yet for this article.
December 13, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29205851/regulated-cell-death-of-lymphoma-cells-after-graded-mitochondrial-damage-is-differentially-affected-by-drugs-targeting-cell-stress-responses
#17
Tomás Lombardo, Martín Gil Folgar, Luciana Salaverry, Estela Rey-Roldán, Elida M Alvarez, María C Carreras, Laura Kornblihtt, Guillermo A Blanco
Collapse of the mitochondrial membrane potential (MMP) is often considered the initiation of regulated cell death (RCD). Carbonyl cyanide 3-chlorophenylhydrazone (CCCP) is an uncoupler of the electron transport chain (ETC) that facilitates the translocation of protons into the mitochondrial matrix leading to the collapse of the MMP. Several cell stress responses such as mitophagy, mitochondrial biogenesis and the ubiquitin proteasome system, may differentially contribute to restrain the initiation of RCD depending on the extent of mitochondrial damage...
December 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29193827/response-to-the-letter-to-the-editor-regarding-baclofen-and-alcohol-dependent-patients-a-real-risk-of-severe-self-poisoning
#18
LETTER
David Boels, Caroline Victorri-Vigneau, Marie Grall-Bronnec, Ali Touré, Marion Brunet, Jean-François Hamel, Gaël Le Roux
No abstract text is available yet for this article.
November 29, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29178257/gender-specific-association-between-abcc2-24c-t-snp-and-reduction-in-triglycerides-in-chilean-patients-treated-with-atorvastatin
#19
Y Prado, A Arancibia, T Zambrano, L A Salazar
Statins are the first-line therapy prescribed to lower plasma cholesterol levels. Although being safe and showing several beneficial cholesterol-independent pleiotropic effects, a significant variability regarding statin's therapeutic goals has been abundantly documented, but less understood. We aimed to investigate the influence of the ABCC2 -24C>T single nucleotide polymorphism on Chilean hypercholesterolaemic subjects treated for 4 weeks with 10 mg/day atorvastatin. A total of 127 individuals medicated with atorvastatin 10 mg/day/4 weeks were included...
November 27, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29171155/interactions-of-2s-6s-2r-6r-hydroxynorketamine-a-secondary-metabolite-of-r-s-ketamine-with-morphine
#20
Tuomas O Lilius, Hanna Viisanen, Viljami Jokinen, Mikko Niemi, Eija A Kalso, Pekka V Rauhala
Ketamine and its primary metabolite norketamine attenuate morphine tolerance by antagonising N-methyl-D-aspartate (NMDA) receptors. Ketamine is extensively metabolised to several other metabolites. The major secondary metabolite (2S,6S;2R,6R)-hydroxynorketamine (6-hydroxynorketamine) is not an NMDA antagonist. However, it may modulate nociception through negative allosteric modulation of α7 nicotinic acetylcholine receptors. We studied whether 6-hydroxynorketamine could affect nociception or the effects of morphine in acute or chronic administration settings...
November 24, 2017: Basic & Clinical Pharmacology & Toxicology
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