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Fundamental & Clinical Pharmacology

Jonaz Font, Mathilda Simeon, Christophe Simard, Stéphane Allouche, Anne-Flore Plane, Virginie Ferchaud, Marie Brionne, René Rouet, Marie Nowoczyn, Alain Manrique, Paolo Emilio Puddu, Paul Milliez, Joachim Alexandre
Whether oral anti-coagulants, vitamin K antagonists (VKAs) and non-vitamin K oral anticoagulant (NOACs) frequently prescribed to atrial fibrillation (AF) patients, do themselves have a pro- or anti-arrhythmic effect have never been addressed. Transmembrane action potentials were recorded in an acute rabbit model of superfused pulmonary veins (PVs) sleeves preparations using standard microelectrode technique. Fluindione 10 μmol/L (n = 6) increased the AP (action potential) duration (APD), induced a significantly Vmax depression (from 95±14 to 53±5 V/s, P < 0...
March 11, 2018: Fundamental & Clinical Pharmacology
Iman Fatemi, Sara Heydari, Ayat Kaeidi, Ali Shamsizadeh, Elham Hakimizadeh, Amin Khaluoi, Mohammad Allahtavakoli
Metformin (Met) has been shown to have pleiotropic effects such as neuroprotective, antioxidant and anti-inflammatory properties making that a potential candidate for the treatment of central nervous system (CNS) disorders. The present study was designed to investigate the possible effect of Met on the D-galactose (D-gal)-induced aging in ovariectomized mice. The female mice underwent bilateral ovariectomy. D-gal was administered orally at a dose of 500 mg/kg and Met was administrated orally at doses of 1 and 10 mg/kg for six weeks...
March 7, 2018: Fundamental & Clinical Pharmacology
Gokhan Zengin, Devina Lobine, Adriano Mollica, Marcello Locatelli, Simone Carradori, Mohamad Fawzi Mahomoodally
The ethyl acetate, methanolic, and water extracts of Fibigia eriocarpa were assessed for a panoply of bioactivities. Total phenolic and flavonoid content were quantified as well as individual phenolic compounds by HPLC-DAD. The in-vitro antioxidant and enzyme (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, α-amylase, and α-glucosidase) inhibitory potential of the extracts were evaluated. In silico molecular docking was used to investigate possible interaction between dominant compounds and selected enzymes...
March 5, 2018: Fundamental & Clinical Pharmacology
Joseph Rwagitinywa, Maryse Lapeyre-Mestre, Robert Bourrel, Jean-Louis Montastruc, Agnès Sommet
Adherence to antiretroviral (ARV) is crucial to achieve viral load suppression in HIV-infected patients. This study aimed to compare adherence to generic multi-tablet regimens (MTR) ver-sus brand MTR likely to incorporate ARV drugs without breaking fixed-dose combinations (FDC) and brand single-tablet regimens (STR) likely to incorporate generics by breaking the FDC. Patients aged of 18 years or over, exposed to one of the generic or the brand of lamivu-dine (3TC), zidovudine/lamivudine (AZT/TC), nevirapine (NVP), or efavirenz (EFV), or the brand STR of efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF)...
March 5, 2018: Fundamental & Clinical Pharmacology
Saeed Mehrzadi, Manijeh Motevalian, Mozhgan Rezaei Kanavi, Iman Fatemi, Habib Ghaznavi, Mansoor Shahriari
Diabetic retinopathy (DR) is one of the most common and serious microvascular complications of diabetes. The aim of the present study was to evaluate the effects of melatonin (MEL) on retinal injury in diabetic rats. In this study, 21 rats were randomly divided into three groups: control, diabetic, diabetic + MEL. Streptozotocin (STZ) was used to induce diabetes at a dose of 50 mg/kg, i.p. and blood glucose was measured to choose the diabetic rats for the study. MEL (20 mg/kg) was given orally for 7 weeks in diabetic rats starting one week after induction of diabetes...
March 1, 2018: Fundamental & Clinical Pharmacology
Segolene Gaillard, Salma Malik, Jenny Preston, Begonya Nafria Escalera, Pamela Dicks, Nathalie Touil, Sandrine Mardirossian, Joana Claverol-Torres, Behrouz Kassaï
Children and young people are seen as fundamental to the design and delivery of clinical research as active and reflective participants. In Europe, involvement of children and young people in clinical research is promoted extensively in order to engage young people in research as partners and to give them a voice to raise their own issues or opinions and for their involvement in planning and decision making in addition to learning research skills. Children and young people can be trained in clinical research through participation in young person advisory groups (YPAGs)...
February 19, 2018: Fundamental & Clinical Pharmacology
Nair Anupama, G Sindhu, K G Raghu
Metabolic syndromes (MS) are a cluster of disorders like obesity, hypertension, dyslipidemia, and diabetes. Cardiometabolic syndrome (CMS), a branch of MS, is a group of diseases affecting cardiovascular, renal, metabolic, prothrombotic and inflammatory abnormalities due to defects in energy metabolism. Since the emergence of molecular biology and the discovery of pathogenic mitochondrial DNA defect in the 1980s, research advances has revealed a number of common human disease involving mitochondrial dysfunction...
February 17, 2018: Fundamental & Clinical Pharmacology
Sylvain Couderc, Maryse Lapeyre-Mestre, Robert Bourrel, Paul Carle, Jean-Louis Montastruc, Agnès Sommet
The aim of this study was to compare the infectious risk between a group of psoriasis patients treated by Biological Drugs (BD) and a group treated by Traditional Systemic Treatments (TST). We built a retrospective observational cohort study from the French health insurance database in the Midi-Pyrénées area (2.9 million inhabitants, South West of France) using data from 01/01/2010 to 12/31/2013. We compared the infectious risk between 'exposed' patients treated with BD (adalimumab, etanercept, infliximab or ustekinumab) and 'unexposed' patients treated by TST (phototherapy, acitretin, methotrexate or cyclosporine)...
February 15, 2018: Fundamental & Clinical Pharmacology
Virginia Neyro, Valéry Elie, Yves Médard, Evelyne Jacqz-Aigrain
Growth and maturation changes are mainly responsible for differences in drug pharmacokinetics and pharmacodynamics observed between adults and children, especially neonates. Ontogeny of drug metabolizing enzymes and transporters play an important role in drugs inter-individual pharmacokinetic variability but data are limited in both term and preterm neonates. This study aimed to characterize mRNA expression of the main drug metabolizing enzymes and transport proteins involved in drug disposition, using umbilical cord blood (UCB), according to gender, gestational age and genetic background...
February 13, 2018: Fundamental & Clinical Pharmacology
Azadeh Aminzadeh, Saeed Mehrzadi
Homocysteine (Hcy) is a major risk factor for vascular disease and is closely associated with endothelial dysfunction. Melatonin is a neurohormone that is mostly produced by the pineal gland. Studies have reported that melatonin exhibits neuroprotective effects in several neurodegenerative disorders. The aim of the current study was to investigate the possible protective effect of melatonin against Hcy-induced endothelial cell apoptosis in human umbilical vein endothelial cells (HUVECs) and to explore the underlying mechanisms...
February 13, 2018: Fundamental & Clinical Pharmacology
Emilie Jouanjus, Grégory Guernec, Maryse Lapeyre-Mestre
Diversion of prescription drugs is difficult to assess in quality and quantity. This study aimed to characterize diversion of prescription drugs in France through a comparative analysis of falsified prescriptions collected during three periods from 2001 to 2012. The data recorded in a national program which records all falsified prescriptions presented to community pharmacies were studied. Included data regarded: subjects, prescription forms and drugs. Description of the dataset in 3 periods (2001-2004, 2005-2008, and 2009-2012) was completed with clustering analyses to characterize profiles of prescriptions and subjects associated with the most reported drugs...
February 13, 2018: Fundamental & Clinical Pharmacology
Paul Carrier, Véronique Loustaud-Ratti
Hepatic encephalopathy (HE) management is a hard and unavoidable clinical challenge in cirrhotic patients [1]. This neuropsychological complex syndrome ranges from weak behavior abnormalities to deep coma. Indeed, the presence of HE is a bad prognostic marker, with a mortality rate higher than 50% in the year following the first symptoms [2,3]. Despite its frequency and numerous dedicated studies, pathophysiology is not totally understood [4]. The main documented physiological factors are impaired ammonia metabolism and specific inflammation linked to liver disease [5,6]...
February 11, 2018: Fundamental & Clinical Pharmacology
Jaspreet Kalra, Suresh Babu Mangali, Audesh Bhat, Indu Dhar, Mary Priyanka Udumula, Arti Dhar
Double stranded RNA (dsRNA) activated protein kinase R (PKR), a ubiquitously expressed serine/threonine kinase is a key inducer of inflammation, insulin resistance and glucose homeostasis in obesity. Recent studies have demonstrated that PKR can respond to metabolic stress in mice as well as in humans. However the underlying molecular mechanism is not fully understood. The aim of the present study was to examine the effect of high fructose (HF) in cultured renal tubular epithelial cells (NRK 52E) derived from rat kidney and to investigate whether inhibition of PKR could prevent any deleterious effects of HF in these cells...
February 11, 2018: Fundamental & Clinical Pharmacology
Basak Donertas, Cigdem Cengelli Unel, Sule Aydin, Emel Ulupinar, Orhan Ozatik, Bilgin Kaygisiz, Engin Yildirim, Kevser Erol
Cisplatin is a widely-used antineoplastic agent in the treatment of various cancers. Peripheral neuropathy is a well-known side effect of cisplatin and has potential to result in limiting and/or reducing the dose, decreasing the quality of life. Thus, effective treatments are needed. Agmatine is an endogenous neuromodulator has been shown to exert antiallodynic effects in various animal studies. The first aim of this study was to investigate the in vitro effects of agmatine on cisplatin-induced neurotoxicity...
January 29, 2018: Fundamental & Clinical Pharmacology
Hyun-Ja Jeong, Myoung-Schook Yoou, Na-Ra Han, Sung Yeoun Hwang, Kyoung Wan Yoon, Hyung-Min Kim
HM0601 consists of Allium hookeri and Lycium chinense fruit and contains a lot of rutin. Here we ascertained whether HM0601 and its major compound rutin reduce proliferation of human mast cell line, HMC-1 under thymic stromal lymphopoietin (TSLP) stimulation. Therapeutic rutin or HM0601 treatment considerably reduced proliferation of mast cells without exposing activated HMC-1 cells to any cytotoxicity. Reduced levels of mouse double minute 2 and phosphorylated-signal transducers and activators of transcription 6 were accompanied by treatment with rutin or HM0601...
January 25, 2018: Fundamental & Clinical Pharmacology
Melissa Yelehe-Okouma, Julie Czmil-Garon, Elise Pape, Nadine Petitpain, Pierre Gillet
Aseptic meningitis associates a typical clinical picture of meningitis with the absence of bacterial or fungal material in the cerebrospinal fluid. Drug-induced aseptic meningitis (DIAM) may be due to two mechanisms: (i) a direct meningeal irritation caused by the intrathecal administration of drugs and (ii) an immunologic hypersensitivity reaction to a systemic administration. If the direct meningeal irritation allows a rather easy recognition, the immunologic hypersensitivity reaction is a source of challenging diagnostics...
January 24, 2018: Fundamental & Clinical Pharmacology
Yan Jin, Fang Wei, Xiaoli Dai, Min Qi, Yukui Ma
The present study aimed to investigate the anti-inflammatory effect of 4-methylcyclopentadecanone (4-MCPC) in rats suffering from a cerebral ischemia/ reperfusion (I/R) injury. In this study, the focal cerebral ischemia in rats was induced by middle cerebral artery occlusion (MCAO) for 2 h, and the rats were treated with 4-MCPC (8 mg/kg) just 0.5 h before reperfusion. The ischemic infarct volume was recorded 24 h after the MCAO. In addition, myeloperoxidase (MPO) activity and TNF-α and IL-1β levels in the ischemic cerebral cortex were determined by ELISA, while nuclear translocation of NF-κB p65 subunit and expression of p-IκBα were investigated by western blotting...
January 18, 2018: Fundamental & Clinical Pharmacology
Liselotte Pochard, Julie Dupouy, Elisabeth Frauger, Adeline Giocanti, Joëlle Micallef, Maryse Lapeyre-Mestre
Pregnancy can be a motivation for decrease in drug abusing but may also represent a period of high vulnerability for relapse.We aimed to assess psychoactive substance use among women with substance use disorders followed in addiction care centers in France. We analyzed data from women aged 15-44 years included in the 'Observation of illegal drugs and misuse of psychotropic medication survey' (OPPIDUM), an annualcross-sectional survey collecting details on psychoactive substances used. Characteristics of women included in 2005 to 2012 yearly surveys were compared depending on their pregnant or not pregnant status...
January 16, 2018: Fundamental & Clinical Pharmacology
Caroline Perrin-Sarrado, Fatima Dahboul, Pierre Leroy, Isabelle Lartaud
S-nitrosoglutathione (GSNO), which is involved in the transport and the storage of NO, induces vasorelaxation. It requires gamma-glutamyl-transferase (GGT), an enzyme present on the endothelium, to transfer NO into the cell. We evaluated whether aging and hypertension, which induce NO-related dilating dysfunction, are associated with decreased vascular GGT activity and modify the vasorelaxant effect of GSNO. Thoracic aortic rings isolated from male Spontaneous Hypertensive Rats (SHR) and Wistar Kyoto Rats (WKY) aged 20-22 (adult) or 57-60 weeks (mature) were preconstricted with phenylephrine, then submitted to concentration-vasorelaxant response curves (maximal response: Emax ; pD2 ) to GSNO and carbachol (the latter to measure NO-related dilating function)...
January 16, 2018: Fundamental & Clinical Pharmacology
Thomas Duflot, Aude Marie-Cardine, Céline Verstuyft, Bruno Filhon, Tony Pereira, Nathalie Massy Guillemant, Robinson Joannidès, Jérémy Bellien, Fabien Lamoureux
Ifosfamide (IFA) is a potent alkylating antitumoral agent but its use is limited by neurological side effects. IFA is a racemic mixture of two enantiomeric forms, R-IFA and S-IFA with a stereoselective metabolism by CYP3A4 and CYP2B6, leading either to bioactive or to toxic pathways. In 3 consecutive cases of pediatric patients who exhibited ifosfamide-induced encephalopathy (IIE), genotyping of clinically relevant single nucleotide polymorphisms associated with decreased CYP3A4 and CYP2B6 activities was performed...
January 10, 2018: Fundamental & Clinical Pharmacology
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