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Fundamental & Clinical Pharmacology

Xuejia Zhai, Yiming Feng, Jun Liu, Jie Li, Yan Zong, Tuo Zhan, Shenrong Gao, Yi Lv
Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide, CAP) is an important ingredient in spicy foods consumed throughout the world. Vinblastine (VBL) is a naturally occurring alkaloid prescribed to cancer patients. Many cancer patients treated with VBL were taking CAP at the same time. This study attempted to investigate the effect of CAP on the pharmacokinetics of VBL, which is the substrate of CYP3A, P-gp, and Mrp2. CAP, cyclosporine (CsA) or olive oil was given to rats for seven consecutive days and on the seventh day VBL (1...
January 11, 2019: Fundamental & Clinical Pharmacology
Minh Quan Pham, Thi Hoai Van Tran, Quoc Long Pham, Jean Edouard Gairin
Liver cancer, of which human hepatocellular carcinoma (HCC) is the most common type, represents the second most common cause of death from cancer worldwide. To date, treatments remain mostly ineffective and efforts are made to discover new molecules or therapeutic strategies against HCC. Mortalin, an hsp70 chaperone protein, is overexpressed in various cancer, including HCC. Mortalin sequesters p53 into the cytoplasm, thereby inhibiting its translocation to the nucleus and consequently, its cellular functions...
January 9, 2019: Fundamental & Clinical Pharmacology
Cécile Conte, Robert Bourrel, Fabien Despas, Maryse Lapeyre-Mestre
Patients suffering from B-cell non-Hodgkin lymphomas (B-NHL) have an increased likelihood of being exposed to proton pump inhibitors (PPIs), related to several factors which have been reported in the literature. PPIs are among the drugs most likely to be prescribed inappropriately. Consequently, B-NHL patients could be particularly at risk of inappropriate PPIs prescription, with potential adverse events. We aimed to evaluate the incidence of PPIs use and to identify factors associated with PPIs initiation during the active treatment phase of B-NHL...
January 9, 2019: Fundamental & Clinical Pharmacology
Masahiko Gosho
Rhabdomyolysis is one of the most concerning complications of antidyslipidemic drugs. Most patients with dyslipidemia take multiple medications. Our objective was to explore which two-drug combinations lead to a higher risk of rhabdomyolysis. We analyzed data from the Japanese Adverse Drug Event Report (JADER) database between April 2004 and September 2017. The primary outcome was the report of rhabdomyolysis. We assessed the risk of rhabdomyolysis for the two-drug concomitant use of antidyslipidemic drugs (statin, fibrate, and ezetimibe) with antihypertensive and antidiabetic medications...
December 21, 2018: Fundamental & Clinical Pharmacology
Delphine Viard, Nadège Parassol-Girard, Serena Romani, Elise Van Obberghen, Fanny Rocher, Sofia Berriri, Milou-Daniel Drici
Since patients may report spontaneously adverse-events associated with their medications, such notifications are constantly on the rise. In 2017, an unexpected rise of notifications associated with the marketing of Levothyrox® new formula, differing from the 30 year-old drug only by minor elements, occurred in France amidst widespread media coverage. Not much, if any, scientific or pharmacological rationale was identified to explain that signal. This led us to focus on the profile and the clinical characteristics of these patient notifications and compare them to those associated with other drugs...
December 21, 2018: Fundamental & Clinical Pharmacology
Jacques Bouget, Frédéric Balusson, Lucie-Marie Scailteux, Maxime Maignan, Pierre-Marie Roy, Erwan L'her, Laure Pavageau, Emmanuel Nowak
Bleeding represents the most recognised and feared complications of antithrombotic drugs including oral anticoagulants. Previous studies showed inconsistent results on the safety profile. Among explanations, bleeding definition could vary and classification bias exist related to the lack of medical evaluation. To quantify the risk of major haemorrhagic event and event-free survival associated with antithrombotic drugs (Vitamin K Antagonist [VKA], non-VKA anticoagulant [NOAC], antiplatelet agent, parenteral anticoagulant) in 2012-2015, we linked the French nationwide Health Insurance database (SNIIRAM) with a local "emergency database" (clinical and biological data collected in clinical records)...
December 10, 2018: Fundamental & Clinical Pharmacology
Diogo Van Bavel, Roger de Moraes, Eduardo Tibirica
The incidence of cardiovascular diseases in vegetarian individuals is lower than that in the general population. Nevertheless, individuals who adhere to vegan diets have a higher prevalence of hyperhomocysteinemia with eventual adverse effects on vascular reactivity. Creatine supplementation (CrS) reduces plasma homocysteine levels and enhances vascular reactivity in the microcirculation. Thus, we investigated the effects of CrS on systemic microcirculation and homocysteine blood levels in strict vegan subjects...
December 3, 2018: Fundamental & Clinical Pharmacology
Ewa Kędzierska, Ferdinando Fiorino, Ewa Gibuła, Angela Corvino, Flavia Giordano, Mariola Herbet, Jarosław Dudka, Ewa Poleszak, Piort Wlaź, Jolanta H Kotlińska
Anxiety disorder is a great challenge for modern psychopharmacology. Although a variety of single drugs are used in the treatment of anxiety, it is important to search for new therapeutics with faster onset of action, fewer side effects and higher efficacy. In this work, we studied the possible anxiolytic action mechanism of two new arylpiperazine derivatives: compounds 4p N-(3-(4-(piperonyl)piperazin-1-yl)propyl)isonicotinamide and 3o N-(2-(4-(pyrimidin-2-yl)piperazin-1-yl)ethyl)picolinamide, focusing on their effects on the GABA-ergic and 5-HT systems...
December 2, 2018: Fundamental & Clinical Pharmacology
Xavier Humbert, Sophie Fedrizzi, Basile Chrétien, Marion Sassier, Haleh Bagheri, Sandrine Combret, Milou-Daniel Drici, François Le Bas, Paolo E Puddu, Joachim Alexandre
Drug-induced hypertension was described with several pharmacological classes, especially with serotonin reuptake inhibitors (SRIs). However, this link has remained controversial: the French summary of product characteristics specify a risk of hypertension only with paroxetine and sertraline. To identify a possible class effect common to all SRIs, our study investigated the reports of hypertension associated with SRIs in two pharmacovigilance databases. Two different types of investigations were performed: (1) a comparative study in VigiBase® , which is the World Health Organization (WHO) pharmacovigilance database (PVDB), from where notifications of hypertension with six SRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) were extracted...
November 29, 2018: Fundamental & Clinical Pharmacology
Yanfang Cao, Yijie Cheng, Awais Ullah Ihsan, Farhan Ullah Khan, Xiaohui Zhou
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease of unclear etiology. Precise treatment of CP/CPPS is not available due to lack of specific cause; however, autoimmunity is the most valid theory. We develop a new treatment strategy that involves synthesis and coupling of biodegradable nanoparticles to antigenic T2 peptide to induce immune tolerance in CP/CPPS mice models. 50 male C57BL/6 mice were randomized into five groups, i.e. naïve, Model, PLGA-PEMA, PLGA-PEMA-OVA323-339 , and PLGA-PEMA-T2 group...
November 24, 2018: Fundamental & Clinical Pharmacology
Gisèle Pickering, Nicolas Macian, Isabelle Papet, Christian Dualé, Catherine Coudert, Bruno Pereira
Paracetamol (APAP) may lead to hepatic changes even at therapeutic dosages. Glutathione (GSH) plays a pivotal role in APAP metabolism as it allows the detoxification of a toxic metabolite. N-Acetylcysteine (NAC) is APAP antidote, is also largely used as a mucoactive drug and is often associated with APAP. This study aims at evaluating if 1- NAC modifies APAP pain efficacy and 2- NAC prevents glutathione depletion with APAP at therapeutic doses. This double-blind randomized controlled study (NCT02206178) was carried out in 24 healthy volunteers...
November 24, 2018: Fundamental & Clinical Pharmacology
Lucie Javot, Elise Pape, Mélissa Yelehe-Okouma, Emilie Barotte, Emmanuelle Divoux, Pierre Gillet, Nicolas Gambier, Julien Scala-Bertola
Amiodarone treatment is contraindicated during breastfeeding. As the regional pharmacovigilance center, we were contacted for information relative to the possibility of breastfeeding after single intravenous administration of 450 mg amiodarone to a breastfeeding woman. A monitoring of amiodarone concentration in plasma and milk was performed in the mother. At day 4, milk concentration of amiodarone reached a peak (233 μg/L) and milk to plasma ratio was determined to 3.5. Milk concentration was still detectable at day 10 (132 μg/L)...
November 24, 2018: Fundamental & Clinical Pharmacology
Ismail O Ishola, Onyinyechi E Akataobi, Azeez A Alade, Olufunmilayo O Adeyemi
There is a growing number of epidemiological and molecular studies which suggest that diabetes is associated with an increased risk of Parkinson's disease (PD). Hence, in this study, the effect of glimepiride (GPD), a sulphonylurea (antidiabetic) on paraquat-induced Parkinsonism was evaluated in mice. Thirty-six mice were randomly divided into six groups (n = 6) and treated orally for 21 consecutive days as follows: Group 1: vehicle (10 mL/kg), Group 2: paraquat (PQT) (10 mg/kg, i.p., twice per week for 3 weeks), Group 3-5: glimepiride (1, 2 or 4 mg/kg) + PQT (10 mg/kg, i...
November 19, 2018: Fundamental & Clinical Pharmacology
Brendan Le Daré, Tatiana Victoni, Aude Bodin, Manuel Vlach, Elise Vene, Pascal Loyer, Vincent Lagente, Thomas Gicquel
Alcohol consumption is considered to be the third leading cause of death in the United States. In addition to its direct toxicity, ethanol has two contrasting effects on the immune system: the nucleotide oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome is inhibited by acute ethanol exposure but activated by chronic ethanol exposure. Purinergic receptors (especially the P2X7 receptor) are able to activate the NLRP3 inflammasome, and are involved in many ethanol-related diseases (such as gout, pulmonary fibrosis, alcoholic steatohepatitis and certain cancers)...
November 17, 2018: Fundamental & Clinical Pharmacology
Florian Lemaitre, Nolwen Lorcy, Camille Tron, Léonard Golbin, Antoine Petitcollin, Marie-Clémence Verdier, Cécile Vigneau, Eric Bellissant
In liver transplantation, tacrolimus trough concentrations (Cmin) above 20 ng/mL during the first days led to worse outcome at 1 year but data in the kidney transplant (KT) era are scarce. The aim of this study was to evaluate the impact of tacrolimus overexposure during the first week post-transplantation on the kidney function (KF) of KT recipients. In this retrospective study, 105 KT recipients were attributed to overexposure group (OG) or normal group according to their Cmin during the first week of treatment...
November 15, 2018: Fundamental & Clinical Pharmacology
Luis Hermenegildo Martín Arias, Antonio Martín González, Rosario Sanz Fadrique, Esther Salgueiro Vázquez
Prior meta-analyses have shown a higher gastrointestinal risk of nonselective NSAIDs versus placebo and a lower gastrointestinal risk of coxibs versus nonselective NSAIDs. However, the available data about gastrointestinal risk for coxibs versus placebo are scarce. The aim of this study was to review the current evidence on the use of coxibs and to evaluate the risk of gastrointestinal adverse outcomes (GAO) associated with coxibs versus nonexposed. Search was conducted on PubMed and Embase databases. We selected cohort observational, case-control, nested case-control and case-crossover studies that reported the risk of GAO associated with coxibs versus nonexposed as relative risk (RR), odds ratio (OR), hazard ratio (HR) or incidence rate ratio (IRR)...
November 1, 2018: Fundamental & Clinical Pharmacology
Justine Benevent, Caroline Hurault-Delarue, Mélanie Araujo, François Montastruc, Jean-Louis Montastruc, Isabelle Lacroix, Christine Damase-Michel
Childhood digestive disorders are a common occurrence, and are sometimes unexplained. Maternal medication during the development of the foetus' digestive system may contribute to the increase of childhood digestive disorders, especially with drugs acting on the cholinergic system. This study investigated the association between prenatal exposure to drugs with atropinic properties and the use of digestive disorder medications in childhood (0 - 3 years). Children from POMME (PrescriptiOn Médicaments Mères Enfants), a French database of reimbursed drugs for pregnant women and their children, were included (N=8,372)...
October 26, 2018: Fundamental & Clinical Pharmacology
Marzieh Khademi, Razieh Taghizadeh Ghavamabadi, Mohammad Mohsen Taghavi, Ahmad Shabanizadeh, Mehdi Shariati-Kohbanani, Mahsa Hassanipour, Zahra Taghipour
Fluoxetine is one of the most commonly used antidepressants. Fluoxetine could prevent the mesenchymal stem cells differentiation in lung fetus of rat. Moreover, the mesenchymal stem cells are also present in adult tissues. Therefore, in the current study, we aimed to investigate the effects of fluoxetine on both proliferation and adipogenic/osteogenic differentiation of human adipose-derived stem cells (ADSCs). After culturing of human ADSCs, these cells were treated with two concentrations of fluoxetine (10 and 20 μM)...
October 25, 2018: Fundamental & Clinical Pharmacology
Dominique Vodovar, Bruno Megarbane
No abstract text is available yet for this article.
December 2018: Fundamental & Clinical Pharmacology
Maryse Lapeyre-Mestre
No abstract text is available yet for this article.
December 2018: Fundamental & Clinical Pharmacology
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