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Fundamental & Clinical Pharmacology

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https://read.qxmd.com/read/31058354/is-tnf-inhibitor-exposure-a-risk-factor-for-amyotrophic-lateral-sclerosis
#1
Nadine Petitpain, David Devos, Haleh Bagheri, Fanny Rocher, Aurore Gouraud, Kamel MAsmoudi, Antoine Coquerel
OBJECTIVES: TNFα modulation has been reported to be either beneficial or detrimental in amyotrophic lateral sclerosis (ALS) and therefore appears as a key issue. We analyzed the relationship between TNFα inhibitor (TNFi) exposure and ALS. METHOD: We performed descriptive analysis of ALS reports in patients treated with TNFi, registered in the French Pharmacovigilance Database (FPvD) and disproportionality analyses by the "case"/"non-case" method in FPvD and worldwide database (Vigibase® )...
May 6, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/31058344/simvastatin-enhances-chemotherapy-in-cervical-cancer-via-inhibition-of-multiple-prenylation-dependent-gtpases-regulated-pathways
#2
Qin Pan, Jiazhen Xu, Liang Ma
Aberrant activation of GTPases is common in cervical cancer and their proper biological functions largely depend on a post-translational modification termed prenylation. Simvastatin is a cholesterol-lowering drug via inhibiting HMG-CoA reductase, thereby inhibiting protein prenylation. In this study, we show that simvastatin selectively inhibits proliferation and induces apoptosis in cervical cancer cells while sparing normal cervical epithelial cells. This is achieved by depleting geranylgeranyl pyrophosphate, inhibiting prenylation, decreasing GTPases activities and suppressing the activation of downstream Ras and RhoA signaling...
May 6, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/31044460/blockade-of-angiogenin-by-thalidomide-inhibits-the-tumorigenesis-of-murine-hemangioendothelioma
#3
Lifang Guo, Zirui Wan, Benshan Xu, Lulu Ren, He Liu, Nan Song, Lihong Liu
Thalidomide, a well-known immunomodulatory compound, has an anti-angiogenic activity, which may be utilized for the treatment of angiogenesis-related diseases such as hemangioendothelioma. The aim of present study was to investigate both the anti-tumor role of thalidomide on hemangioendothelioma and the underlying mechanism. By using the xenograft mouse model, we found that thalidomide can inhibit the progression of hemangioendothelioma in vivo. Moreover, thalidomide shows no effect on the proliferation of hemangioendothelioma-derived cells (EOMA), but significantly impairs the pro-angiogenic capacity of the EOMA cells in vitro...
May 1, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/31038767/prediction-of-docetaxel-toxicity-in-older-cancer-patients-a-bayesian-network-approach
#4
Fouzy Khayi, Laurent Lafarge, Catherine Terret, Gilles Albrand, Benoit Falquet, Stéphane Culine, Sophie Gourgou, Michel Ducher, Laurent Bourguignon
Chemotherapy is an essential therapy in the fight against cancer. Polypathology and polymedication are often encountered in elderly patients, making this population especially at risk for adverse drug reactions, and particularly with cytotoxic drugs. The objective of this study was to build a model to predict high-grade toxicity in elderly patients treated with docetaxel. Data from the trial TAX-108 have been used to create the model. The variable to predict was the occurrence of grade 3 or 4 toxicity. The explanatory variables entered in the model were anthropometric and biological characteristics of patients at inclusion; fragility criteria (SMAF, CIRS-G, Performance Status); location of the primary tumor; chemotherapy history, radiotherapy or surgery; weekly dose of docetaxel, cumulative dose administered...
April 30, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/31038766/a-successful-antibiotic-treatment-by-a-new-administration-route-a-case-report-of-a-subcutaneous-administration-of-ceftazidime-and-tobramycin
#5
Dorothée Duron, Sébastien Chanoine, Maud Peron, Marion Lepelley, Benoît Allenet, Olivier Epaulard, Boubou Camara, Pierrick Bedouch
When intramuscular or intravenous administrations of parenteral drugs are not possible, the use of other routes (e.g., subcutaneous route) should be considered.We report a patient with Duchenne Muscular Dystrophy, who was hospitalized for acute pneumonia due to antibiotic-resistant strains of bacteria. Our patient was successfully recovered with antimicrobial therapy by subcutaneous administration of ceftazidime and tobramycin, for which no safety and efficacy data are available in humans. To the best of our knowledge, this case is the first supporting the subcutaneous administration safety and potential efficacy of both ceftazidime and tobramycin in humans...
April 30, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/31013357/tranexamic-acid-through-intravenous-intramuscular-and-oral-routes-an-individual-participant-data-meta-analysis-of-pharmacokinetic-studies-in-healthy-volunteers
#6
Stanislas Grassin-Delyle, Michaela Semeraro, Frantz Foissac, Naim Bouazza, Haleema Shakur-Still, Ian Roberts, Jean-Marc Treluyer, Saïk Urien
BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic drug that reduces surgical blood loss and death due to bleeding after trauma and post-partum haemorrhage. One key issue for treatment success is early administration. While usually given intravenously, oral and intramuscular use would be useful in specific circumstances. Therefore, an understanding of TXA pharmacokinetics when given via different routes is valuable. The aim of this study was to perform an individual participant data meta-analysis of pharmacokinetic studies with TXA given to healthy volunteers via different routes...
April 23, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/31012153/endothelium-dependent-and-endothelium-independent-effects-of-1-nitro-2-propylbenzene-on-rat-aorta
#7
Thiago Brasileiro de Vasconcelos, Helder Veras Ribeiro Filho, Emanuella Feitosa de Carvalho, Teresinha Silva de Brito, Saad Lahlou, Pedro Jorge Caldas Magalhães
A group of nitro compounds contains a benzene ring in a short aliphatic chain with the NO2 group, property that supposedly favors its vasodilator profile. In this study, we evaluated in isolated rat aorta the effects of 1-nitro-2-propylbenzene (NPB), a nitro compound containing the NO2 in the aromatic ring. In aorta precontracted with KCl, NPB (1-3000 μM) induced full endothelium-independent relaxation. In endothelium-intact preparations, phenylephrine-induced contractions were fully relaxed by NPB, effect unaltered by N(ω)-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ)...
April 22, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/31001898/neuroprotective-effects-of-zafirlukast-piracetam-and-their-combination-on-l-methionine-induced-vascular-dementia-in-rats
#8
Ahmed M Fayez, Ahmed S Elnoby, Nada H Elbahnasawy, Omar Hassan
Vascular dementia is considered a vascular cognitive impairment disease caused by neuronal degeneration in the brain. Several studies have supported the hypothesis that oxidative stress and endothelial dysfunction are the main pathogenic factors in vascular dementia. This current study aims to determine the possible neuroprotective effects of zafirlukast, piracetam and the combination of piracetam and zafirlukast on L-methionine-induced vascular dementia in rats. Male Wistar albino rats were divided into five groups...
April 18, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/30951217/felbamate-produces-antidepressant-like-actions-in-the-chronic-unpredictable-mild-stress-and-chronic-social-defeat-stress-models-of-depression
#9
Xiuqin Li, Hongze Wang, Qingnian Chen, Zhiqin Li, Chao Liu, Shengnan Yin, Zhengchen You
Felbamate is an anticonvulsant used in the treatment of epilepsy. In this study, we investigated the antidepressant-like actions of felbamate in mice. The effects of felbamate were first assessed using the forced swimming test (FST) and tail suspension test (TST), and then investigated in the chronic unpredictable mild stress (CUMS) and chronic social defeat stress (CSDS) models of depression. The changes in the hippocampal brain-derived neurotrophic factor (BDNF) signaling cascade after chronic stress and felbamate treatment were also examined...
April 5, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/30903708/treatment-with-either-cox-2-inhibitor-or-5-lox-inhibitor-causes-no-compensation-between-cox-2-pathway-and-5-lox-pathway-in-chronic-aluminum-overload-induced-liver-injury-in-rats
#10
Hui Xia, Qin He, Hong Wang, Yongming Wang, Yang Yang, Yuke Li, Jiahua Zhang, Zhihao Chen, Junqing Yang
This study was designed to observe the compensation between cyclooxygenase-2 pathway and 5-lipoxygenase pathway in chronic aluminum overload-induced liver injury rats. A rat hepatic injury model of chronic aluminum injury was established by the intragastric administration of aluminum gluconate (Al3 + 200 mg·kg-1 per day, 5 days a week for 20 weeks). The COX-2 inhibitor [meloxicam (1 mg·kg-1 )] and 5-LOX inhibitor [caffeic acid (30 mg·kg-1 )] were intragastrically administered 1h after aluminum administration...
March 23, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/30900301/effects-of-dietary-supplementation-with-creatine-on-homocysteinemia-and-systemic-microvascular-endothelial-function-in-individuals-adhering-to-vegan-diets
#11
EDITORIAL
Rafael Deminice
No abstract text is available yet for this article.
March 21, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/30866091/inflammatory-process-in-parkinson-disease-neuroprotection-by-neuropeptide-y
#12
Stéphanie Pain, Sylvie Bodard, Zuhal Gulhan, Jackie Vergote, Sylvie Chalon, Afsaneh Gaillard
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway. Interestingly, it has already been shown that an intracerebral administration of neuropeptide Y (NPY) decreases the neurodegeneration induced by 6-hydroxydopamine (6-OHDA) in rodents and prevents loss of dopamine (DA) and DA transporter density. The etiology of idiopathic PD now suggest that chronic production of inflammatory mediators by activated microglial cells mediates the majority of DA-neuronal tissue destruction...
March 13, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/30861604/procyanidin-b2-from-lotus-seedpod-regulate-no-adma-ddah-pathway-to-treat-insomnia-in-rats
#13
Hong-Bo Xiao, Yi-Shan Wang, Lin Liang, XiangYang Lu, Zhi-Liang Sun
Recent studies show that nitric oxide / asymmetric dimethylarginine /dimethylarginine dimethylaminohydrolase (NO/ADMA/DDAH) pathway may contribute to the development of sleep disorder. The objective of this study was to explore the inhibitory effect of procyanidin B2 from lotus seedpod (LSPC), a naturally occurring catechin compound, on insomnia and the mechanisms involved. The experiments were performed in brain from Sprague-Dawley rat control and insomniac rats treated or not with LSPC (15, 30, 45 mg/kg, intragastrically) for 7 days...
March 12, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/30860620/cyclooxygenase-selectivity-and-chemical-groups-of-non-steroidal-anti-inflammatory-drugs-and-the-frequency-of-reporting-hypersensitivity-reactions-a-case-non-case-study-in-vigibase
#14
Mohammad Bakhriansyah, Ronald H B Meyboom, Patrick C Souverein, Anthonius de Boer, Olaf H Klungel
The reporting of hypersensitivity reactions (HSRs) among non-steroidal anti-inflammatory drugs (NSAIDs) according to cyclooxygenase (COX) selectivity and chemical groups has not been published yet in one study. This study assessed the reporting frequency of HSRs for NSAIDs based on their relative inhibitory potency towards COX enzymes and chemical groups, including the presence/absence of a functional sulfonamide group, in strata of 5 years after market authorization. A case/non-case study was performed among Individual Case Safety Reports (ICSRs) with NSAIDs as suspected drugs in VigiBase, the WHO spontaneous reporting database...
March 12, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/30851197/potassium-channels-in-vascular-smooth-muscle-a-pathophysiological-and-pharmacological-perspective
#15
REVIEW
Muhammed Fatih Dogan, Oguzhan Yildiz, Seyfullah Oktay Arslan, Kemal Gökhan Ulusoy
Potassium (K+ ) ion channel activity is an important determinant of vascular tone by regulating cell membrane potential (MP). Activation of K+ channels leads to membrane hyperpolarization and subsequently vasodilatation, while inhibition of the channels causes membrane depolarization and then vasoconstriction. So far five distinct types of K+ channels have been identified in vascular smooth muscle cells (VSMCs); Ca+2 -activated K+ channels (BKC a ), voltage-dependent K+ channels (KV ), ATP-sensitive K+ channels (KATP ), inward rectifier K+ channels (Kir ), and tandem-two pore K+ channels (K2 P)...
March 9, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/30849185/non-steroidal-anti-inflammatory-drug-nsaid-prescriptions-from-the-6-th-month-of-pregnancy-impact-of-advice-from-health-authorities
#16
Mélanie Araujo, Caroline Hurault-Delarue, Claire Bouilhac, Dominique Petiot, Justine Benevent, Christophe Vayssière, Sabine Vidal, Jean-Louis Montastruc, Christine Damase-Michel, Isabelle Lacroix
NSAIDs are among the most widely used drugs. On June 2008 and February 2009, Dear Doctor Letters (DDLs) were sent by the French Health Authorities (AFSSAPS) to remind practitioners of risks with NSAIDs after the fifth month of pregnancy. The aim of this study was to evaluate the impact of these letters on NSAID prescriptions during late pregnancy. EFEMERIS is a French database that registers drugs prescribed and reimbursed during pregnancy and outcomes between 2004 and 2015. We performed a descriptive study and a "before-and-after" comparison of NSAID prescriptions between 2 June 2006 and 3 June 2008 ("before group"), and between 1 March 2010 and 1 March 2012 ("after group")...
March 8, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/30811659/urapidil-but-not-dihydropyridine-calcium-channel-inhibitors-preserves-the-hypoxic-pulmonary-vasoconstriction-an-experimental-study-in-pig-arteries
#17
Claire Bopp, Cyril Auger, Alexandre Mebazaa, Girish P Joshi, Valérie B Schini-Kerth, Pierre Diemunsch
Hypoxic pulmonary vasoconstriction (HPV) is a protective mechanism maintaining blood oxygenation by redirecting blood flow from poorly ventilated to well-ventilated areas in the lung. Such a beneficial effect is blunted by antihypertensive treatment with dihydropyridine calcium channel inhibitors. The aim of the present study was to evaluate the effect of urapidil, an antihypertensive agent acting as an α1 adrenergic antagonist and a partial 5-HT1A agonist, on HPV in porcine proximal and distal pulmonary artery rings, and to characterize underlying mechanisms...
February 27, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/30811654/effect-of-x-ray-irradiation-on-pharmacokinetics-of-irinotecan-hydrochloride-and-expression-of-ces1-and-cyp3a1-in-rats
#18
Qiao Yijie, Wang Xuejun, Xin Yuanyao, Nian Yongqiong, Yang Jianxin, Duan Yabin, Li Xiangyang
Concurrent chemoradiation with irinotecan hydrochloride (CPT-11) is accepted for cancer treatment. However, the effects of x-ray irradiation on chemotherapeutics in the plasma remain unclear. We evaluated the pharmacokinetics of CPT-11 in rats after exposure to x-ray irradiation, and examined the changes of protein and mRNA expression of CES1 and CYP3A1. The x-ray irradiation with 1 Gy and 5 Gy was delivered to the whole body of rats. CPT-11 at 30 mg/kg and 60 mg/kg, respectively, was intravenously infused 24 hours after irradiation...
February 27, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/30790345/a-population-analysis-of-the-dgat1-inhibitor-gsk3008356-and-its-effect-on-endogenous-and-meal-induced-triglyceride-turnover-in-healthy-subjects
#19
Malek Okour, Richard A Brigandi, David Tenero
Nonalcoholic steatohepatitis (NASH) is a liver disease in which fatty infiltration is accompanied by liver inflammation. GSK3008356 is under development as a selective inhibitor of diacylglycerol acyltransferase 1 (DGAT1), a key enzyme involved in the formation of triglyceride (TG). Decreased DGAT1 activity can reduce circulating TG and liver TG, and therefore could potentially prevent or treat NASH. The aim of the current study is to develop a population pharmacokinetic-pharmacodynamic (PKPD) model that characterizes the PK disposition of GSK3008356 and its relation to the changes in blood TG...
February 20, 2019: Fundamental & Clinical Pharmacology
https://read.qxmd.com/read/31056815/intravenous-single-administration-of-amiodarone-and-breastfeeding
#20
EDITORIAL
Zoubir Djerada
No abstract text is available yet for this article.
June 2019: Fundamental & Clinical Pharmacology
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