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Basic & Clinical Pharmacology & Toxicology

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https://www.readbyqxmd.com/read/28084056/genetic-influences-of-oprm1-oprd1-and-comt-on-morphine-analgesia-in-a-multi-modal-multi-tissue-human-experimental-pain-model
#1
Lecia Møller Nielsen, Lona Louring Christrup, Hiroe Sato, Asbjørn Mohr Drewes, Anne Estrup Olesen
Human studies on experimentally induced pain are of value to elucidate the genetic influence on morphine analgesia under controlled conditions. The aim of this study was to investigate if genetic variants of mu, kappa and delta opioid receptor genes (OPRM1, OPRK1 and OPRD1) and catechol-O-methyltransferase gene (COMT) are associated with the morphine analgesia. The study was a randomised, double-blind, two-way, cross-over, single-dose study conducted in 40 healthy participants, where morphine was compared with placebo...
January 13, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28064463/global-research-trends-in-lithium-toxicity-from-1913-to-2015-a-bibliometric-analysis
#2
Sa'ed H Zyoud, W Stephen Waring, Waleed M Sweileh, Samah W Al-Jabi
Lithium salts have been used to treat psychiatric disorders since the 1940s and are currently used in prophylaxis and treatment of depression and bipolar disorder. Therefore, we conducted this study to assess lithium toxicity-related publications using bibliometric approaches from a health point of view to assess global research trends in the lithium toxicity field to offer guidance to future research in this field. The data were retrieved from the online version of Scopus database on 6 August 2016. All records with the term "lithium" in the title were retrieved, and those related to lithium toxicity were evaluated...
January 8, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28064437/clinical-pharmacology-research-internships-at-the-interface-of-academia-and-industry-students-perceptions-and-scientific-output
#3
Sebastiaan C Goulooze, Kari L Franson, Adam F Cohen, Robert Rissmann
The Centre for Human Drug Research (CHDR) is a non-profit clinical research institute at the interface between academia and the pharmaceutical industry. CHDR hosts a research internship program for undergraduate (bio)medical students. The aim of this study was i) to investigate the student perceptions of the undergraduate research internship ii) quantify the scientific output related to these internships. We surveyed former interns at the CHDR from the years 2007 - 2014 and quantified their scientific output with a PubMed search...
January 8, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28054752/opposite-modulatory-effects-of-selective-and-non-selective-cyclooxygenase-inhibition-on-cardiovascular-and-autonomic-consequences-of-cyclosporine-in-female-rats
#4
Karim S Ibrahim, Ahmed F El-Yazbi, Hanan M El-Gowelli, Mahmoud M El-Mas
Non-steroidal anti-inflammatory drugs (NSAIDs) and the immunosuppressant drug cyclosporine (CSA) are concurrently administered in arthritis. Here, we investigated whether diclofenac (non-selective inhibitor of cyclooxygenase-1 and 2, COX-1/COX-2), celecoxib (selective COX-2 inhibitor) or SC560 (selective COX-1 inhibitor) interact variably with hemodynamic effects of CSA in conscious female rats. Changes caused by CSA (10 mg/kg i.v.) in blood pressure (BP), heart rate (HR), HR variability (HRV) and myocardial contractility were assessed in absence and presence of individual NSAIDs (10 mg/kg each)...
January 5, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28054742/evaluation-of-dna-damage-in-hepg2-cells-and-mutagenicity-of-garcinielliptone-fc-a-bioactive-benzophenone
#5
Lismare da Silva Prado, Juliana da Silva, Ana Letícia Hilario Garcia, Fernanda Brião Menezes Boaretto, Ivana Grivicich, Lucas Umpierre Conter, Aguisson de Oliveira Salvi, Flávio Henrique Reginatto, Suele Bierhals Vencato, Alexandre de Barros Falcão Ferraz, Jaqueline Nascimento Picada
Garcinielliptone FC (GFC) is a polyprenylated benzophenone isolated from the hexanic extract of Platonia insignis seeds with potential pharmacological effects on the central nervous system. In a pre-clinical study, this compound showed anticonvulsant action, becoming a candidate to treat epilepsy disorders. However, genotoxicological aspects of GFC should be known to ensure its safe use. This study investigated the cytotoxic, genotoxic and mutagenic effects of GFC. Cytotoxicity was evaluated using the colourimetric assay of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) in human hepatoma cells (HepG2) (2 - 100 μg/mL) for 3, 6 and 24 hr...
January 5, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28052578/ticagrelor-increased-adenosine-and-cyclic-adenosine-monophosphate-plasma-concentration-compared-with-clopidogrel-in-acute-coronary-syndromes-patients
#6
Xiao-Ye Li, Qi-Bing Wang, Ying Xue, Jia-Hui Chen, Qian-Zhou Lv
Ticagrelor produces a more potent antiplatelet effect than clopidogrel, and inhibits cellular uptake of adenosine, which is associated with several cardiovascular consequences. We aimed to explore the correlation between adenosine and cyclic adenosine monophosphate (cAMP) plasma concentration and antiplatelet effect by clopidogrel or ticagrelor in acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy (DAPT). We conducted a prospective, observational and single-centre cohort study enrolling 68 patients with non-ST-segment elevation ACS from January 2016 to May 2016...
January 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28032943/mass-spectrometry-based-tools-to-characterize-dna-protein-cross-linking-by-bis-electrophiles
#7
Arnold Groehler, Amanda Degner, Natalia Y Tretyakova
DNA-protein cross-links (DPCs) are unusually bulky DNA adducts that form in cells as a result of exposure to endogenous and exogenous agents including reactive oxygen species, ultraviolet light, ionizing radiation, environmental agents (e.g. transition metals, formaldehyde, 1,2-dibromoethane, 1,3-butadiene) and common chemotherapeutic agents. Covalent DPCs are cytotoxic and mutagenic due to their ability to interfere with faithful DNA replication and prevent accurate gene expression. Key to our understanding of the biological significance of DPC formation is identifying the proteins most susceptible to forming these unusually bulky and complex lesions and quantifying the extent of DNA-protein cross-linking in cells and tissues...
December 29, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28032440/magnolol-attenuates-concanavalin-a-induced-hepatic-fibrosis-inhibits-cd4-t-helper-17-th17-cell-differentiation-and-suppresses-hepatic-stellate-cell-activation-blockade-of-smad3-smad4-signalling
#8
Hongjun Zhang, Baoling Ju, Xiaoli Zhang, Yanfei Zhu, Ying Nie, Yuanhong Xu, Qiuxia Lei
Magnolol is a pharmacological biphenolic compound extracted from Chinese herb Magnolia officinalis, which displays anti-inflammatory and antioxidant effects. This study was aimed at exploring the potential effect of magnolol on immune-related liver fibrosis. Herein, BALB/c mice were injected with concanavalin A (ConA, 8 mg/kg/week) up to 6 weeks to establish hepatic fibrosis, and magnolol (10, 20, 30 mg/kg/day) was given to these mice orally throughout the whole experiment. We found that magnolol preserved liver function and attenuated liver fibrotic injury in vivo...
December 29, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28027430/pharmacological-properties-of-melanin-and-its-function-in-health
#9
Adila Salih ElObeid, Afaf Kamal-Eldin, Mohamed Anwar K Abdelhalim, Adil M Haseeb
The biological pigment melanin is present in most of the biological systems. It manifests a host of biological and pharmacological properties. Its role as a molecule with special properties and functions affecting general health, including photo-protective and immunological action are well recognised. Its antioxidant, anti-inflammatory, immuno-modulatory, radio-protective, hepatic, gastrointestinal and hypoglycaemic benefits have only recently been recognised and studied. It is also associated with certain disorders of the nervous system...
December 27, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28001342/triggering-mechanisms-and-inflammatory-effects-of-combustion-exhaust-particles-with-implication-for-carcinogenesis
#10
J Øvrevik, M Refsnes, M Låg, B Brinchmann, P E Schwarze, J A Holme
A number of biological responses may contribute to the carcinogenic effects of combustion-derived particulate matter (CPM). Here, we focus on mechanisms that trigger CPM-induced pro-inflammatory responses. Inflammation has both genotoxic as well as non-genotoxic implications and is considered to play a central role in development of various health outcomes associated with CPM exposure, including cancer. Chronic, low-grade inflammation may cause DNA damage through a persistent increased level of reactive oxygen species (ROS) produced and released by activated immune cells...
December 21, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28000392/the-antinociceptive-activity-of-geraniol
#11
LETTER
Salvatore Chirumbolo, Geir Bjørklund
No abstract text is available yet for this article.
December 20, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27995743/anticholinergic-exposure-in-a-cohort-of-adults-aged-80-years-and-over-associations-of-the-marante-scale-with-mortality-and-hospitalisation
#12
Maarten Wauters, Therese Klamer, Monique Elseviers, Bert Vaes, Olivia Dalleur, Jan Degryse, Carlos Durán, Thierry Christiaens, Majda Azermai, Robert Vander Stichele
Anticholinergics are frequently prescribed for older adults and can lead to adverse drug events. The novel MARANTE (Muscarinic Acetylcholinergic Receptor ANTagonist Exposure) scale measures the anticholinergic exposure by incorporating potency and dosages of each medication into its calculations. The aims were to assess prevalence and intensity of the anticholinergic exposure in a longitudinal cohort study of community-dwelling patients aged 80 years and over (n=503) and to study the impact on mortality and hospitalisation...
December 20, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27992670/dissection-of-the-effects-of-quercetin-on-mouse-myocardium
#13
Michel Santana Santos, Evaleide Diniz de Oliveira, Artur Santos-Miranda, Jader Santos Cruz, Antônio Nei Santana Gondim, José Evaldo Rodrigues de Menezes-Filho, Diego Santos de Souza, Leidiane Pinho-da-Silva, Itamar Couto Guedes de Jesus, Danilo Roman-Campos, Silvia Guatimosim, Aline Lara, Eduardo Antônio Conde-Garcia, Carla Maria Lins de Vasconcelos
Quercetin is a plant flavonoid with several biological activities. This study aimed to describe quercetin effects on contractile and electrophysiological properties of the cardiac muscle as well as on calcium handling. Quercetin elicited positive inotropism that was significantly reduced by propranolol indicating an involvement of the sympathetic nervous system. In cardiomyocytes, 30 μM quercetin increased ICa,L at 0 mV from -0.95 ± 0.01 A/F to -1.21 ± 0.08 A/F. The membrane potential at which 50% of the channels are activated (V0...
December 19, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27992666/lithium-toxicity-in-a-pregnant-woman
#14
Nasim Zamani, Maryam Paeezi, Hossein Hassanian-Moghaddam
Lithium is recommended in bipolar disorder and can be accompanied by significant toxicity in pregnant women. A 25-year-old single-gestation pregnant woman (28 weeks) was referred with suspicion of lithium toxicity. Serum lithium was 2.1 meq/L. Despite conservative therapy with intravenous fluids, lithium concentration increased to 5.0 meq/L 6 hr post admission mandating an emergent hemodialysis during which foetal heart rate decreased to 90 bpm. The gynaecologist ordered termination of pregnancy while the mother was still on hemodialysis...
December 19, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27992665/naloxone-antagonises-soman-induced-central-respiratory-depression-in-rats
#15
Ranko Škrbić, Miloš P Stojiljković, Slavko S Ćetković, Silva Dobrić, Dejan Jeremić, Maja Vulović
The influence of naloxone on respiration impaired by the highly toxic organophosphate nerve agent soman in anaesthetized rats was investigated. Soman, administered in a dose that was ineffective in blocking the electrically induced contractions of the phrenic nerve-diaphragm preparation in situ, induced a complete block of the spontaneous respiratory movements of the diaphragm, indicating the domination of central over the peripheral effects. Naloxone dose-dependently antagonised the soman-induced respiratory blockade...
December 19, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27987371/synergistic-combination-for-chemoprevention-of-hepatocellular-carcinoma-an-in-silico-and-in-vitro-approach
#16
Savita Mishra, DeepshikhaPande Katare
Combination therapy is one of the best methods to manage the fatality rate in hepatocellular carcinoma (HCC). The current study aimed to formulate a synergistic combination of synthetic and herbal compounds for the treatment of HCC as well as to elucidate a possible signalling mechanism. MTT and enzymatic assay were performed to determine the synergistic effect of drug combination (sorafenib, vitamin K1 and trans-chalcone) on HepG2 cell lines after intoxication with H2 O2 . Protein-protein interaction and docking studies were performed using Pathwaylinker2...
December 17, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27983775/carnitine-and-%C3%AE-butyrobetaine-stimulate-elimination-of-meldonium-due-to-competition-for-octn2-mediated-transport
#17
Edgars Liepinsh, Elina Makarova, Eduards Sevostjanovs, Dace Hartmane, Helena Cirule, Olga Zharkova-Malkova, Solveiga Grinberga, Maija Dambrova
Meldonium (3-(2,2,2-trimethylhydrazinium)propionate) is the most potent clinically used inhibitor of organic cation transporter 2 (OCTN2). Inhibition of OCTN2 leads to a decrease in carnitine and acylcarnitine contents in tissues and energy metabolism optimization-related cardioprotective effects. The recent inclusion of meldonium in the World Anti-Doping Agency List of Prohibited Substances and Methods has raised questions about the pharmacokinetics of meldonium and its unusually long elimination time. Therefore, in this study, the rate of meldonium washout after the end of treatment was tested with and without administration of carnitine, γ-butyrobetaine (GBB) and furosemide to evaluate the importance of competition for OCTN2 transport in mice...
December 16, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27983772/metabolic-response-to-olanzapine-in-healthy-chinese-subjects-with-rs7093146-polymorphism-in-transcription-factor-7-like-2-gene-tcf7l2-a-prospective-study
#18
Qing Li, Dong Guo, Hong Yang, Zhi Ye, Jin Huang, Yan Shu
Olanzapine is a widely used atypical antipsychotic with significant weight gain and other metabolic side effects. The locus of the transcription factor 7-like 2 (TCF7L2) gene is strongly associated with type 2 diabetes (T2D). The goal of this study was to determine whether polymorphic TCF7L2 is involved in the susceptibility to the metabolic changes associated with the atypical antipsychotic agents (AAPs). In this study, a parallel clinical study with 3-day consecutive administration of olanzapine (10 mg/day) was conducted in 17 healthy subjects with a genotype of TCF7L2 rs7903146 CC (N=10) or CT (N=7)...
December 16, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27983767/sulforaphane-improves-neuronal-mitochondrial-function-in-brain-tissue-in-acute-carbon-monoxide-poisoning-rats
#19
Mingjun Bi, Qin Li, Dadong Guo, Xiaoyu Ding, Weikang Bi, Yueheng Zhang, Yong Zou
Carbonmonoxide (CO) poisoning is one of the leading causes of toxicity-related mortality and morbidity worldwide, primarily manifested by acute and delayed central nervous system (CNS) injuries and other organ damages. However, its definite pathogenesis is poorly understood. The aim of the present study was to explore the pathogenesis of the ultrastructural and functional impairment of mitochondria and the protection of sulforaphane (SFP) at different dosages on hippocampus neurons in rats after exposure to CO...
December 16, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27911474/is-chelation-therapy-efficient-for-the-treatment-of-intravenous-metallic-mercury-intoxication
#20
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 outcome, 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 2 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 times...
December 2, 2016: Basic & Clinical Pharmacology & Toxicology
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