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Fundamental & Clinical Pharmacology

Amaurilio Oliveira Nogueira, Yasmin Ingrid Santos Oliveira, Beatriz Lima Adjafre, Maria Elisabete Amaral de Moraes, Gislei Frota Aragão
Protium heptaphyllum Aubl. belongs to the Burseraceae family. It is commonly called "almecegueira" and is known to produce an amorphous resin which has constituents such as α- and β-amyrin, taraxastan-3-oxo-20-ol and sitostenonein. The α- and β-amyrin from P. heptaphyllum have pharmacological activities in several systems, such as central and peripheral nervous system, gastrointestinal tract and immunological system. In the present study, our objective was to review pharmacological activities and to gather more information on the mixture of α- and β-amyrin obtained from P...
July 13, 2018: Fundamental & Clinical Pharmacology
Gaétan Gentile, Maeva Jego, Michel Spadari, Karolina Griffiths, Emilie Jouanjus, Joëlle Micallef
Addictovigilance is a health vigilance dedicated to the survey of medicinal or illicit psychoactive substance use disorders (SUDs). France is the only European country to have a vigilance system specifically dedicated to substances with an abuse/addiction potential. The French Addictovigilance system is organized in a network of regional tertiary centers (called Abuse and Dependence Monitoring Centres, CEIP-Addictovigilance) and works in close collaboration with Regional and National health authorities. Because of the essential and unavoidable nature of their practice in the French Healthcare system, general practitioners (GPs) are key actors to identify and track Addictovigilance signals...
July 12, 2018: Fundamental & Clinical Pharmacology
Tien-Yao Tsai, Iat-Lon Leong, Ka-Shun Cheng, Lian-Ru Shiao, Tzu-Hui Su, Kar-Lok Wong, Paul Chan, Yuk-Man Leung
A pathological feature in atherosclerosis is the dysfunction and death of vascular endothelial cells (EC). Oxidized low-density lipoprotein (LDL), known to accumulate in the atherosclerotic arterial walls, impairs endothelium-dependent relaxation (EDR) and causes EC apoptosis. A major bioactive ingredient of the oxidized LDL is lysophosphatidylcholine (LPC), which at higher concentrations causes apoptosis and necrosis in various EC. There is hitherto no report on LPC-induced cytotoxicity in brain EC. In this work we found that LPC caused cytosolic Ca2+ overload, mitochondrial membrane potential decrease, p38 activation, caspase 3 activation and eventually apoptotic death in mouse cerebral bEND...
July 5, 2018: Fundamental & Clinical Pharmacology
Behnaz Karimi, Mahboobeh Ashrafi, Tahoora Shomali, Azadeh Yektaseresht
Preclinical studies have shown positive effects of statins against specific cancers. The present study aimed to determine the therapeutic effect of simvastatin in 12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer. Female albino mice were divided into two groups, with or without DMBA administration. After tumor appearance, DMBA treated group was further divided into four groups (D1-D4) as control (D1), treated with simvastatin at 80 and 40 mg/kg/day, orally (D2 and D3) and tamoxifen (50 mg/kg/day, orally) treated group (D4)...
July 1, 2018: Fundamental & Clinical Pharmacology
Suchi Raghunathan, Corey L Reynolds, Robert J Schwartz, M David Stewart, Bradley K McConnell
Inbred mouse strains are the most widely used mammalian model organism in biomedical research owing to ease of genetic manipulation and short lifespan; however, each inbred strain possesses a unique repertoire of deleterious homozygous alleles that can make a specific strain more susceptible to a particular disease. In the current study, we report dystrophic cardiac calcinosis (DCC) in C.B-17 SCID male mice at 10 weeks of age with no significant change in cardiac function. Acquisition of DCC was characterized by myocardial injury, fibrosis, calcification, and necrosis of the tissue...
June 30, 2018: Fundamental & Clinical Pharmacology
Bruno Ribeiro Baptista, Nadine Petitpain, Emmanuel Gomez, Melissa Yelehé-Okouma, Simon Valentin, Anne Guillaumot, François Chabot, Ari Chaouat
4-aminopyridine (4-AP) is a recent treatment indicated to improve walking in patient with multiple sclerosis. We report the first case of pulmonary arterial hypertension (PAH) that we attribute to the use of 4-AP. A 64-year-old woman with multiple sclerosis presented with dyspnea. After excluding other secondary causes of pulmonary hypertension, a diagnosis of severe PAH due to 4-AP was made based on right heart catheterization. History revealed that the dyspnea began with the initiation of 4-AP. After discontinuation of 4-AP therapy and initiation of ambrisentan and tadalafil, dyspnea and pulmonary arterial pressure have improved significantly and one specific PAH-treatment was stopped...
June 29, 2018: Fundamental & Clinical Pharmacology
Céline Eiden, Sarah Leone-Burgos, Anaïs Serre, Louise Carton, Marie Gerardin, Reynald Le Boisselier, Valérie Gibaja, Emilie Monzon, Nathalie Fouilhe, Alexandra Boucher, Hélène Peyriere
Ephenidine, diphenidine and methoxphenidine belong to the family of diarylethylamines that are psychoactive substances derived from lefetamine (N, N-di-methyl-1,2-diphenylethylamine, also called L-SPA). These dissociative anesthetic compounds act as potent and selective NMDA receptor antagonists and were recently classified as narcotic drugs in France. The available data suggest a significant risk of psychic and somatic complications. To obtain more information, this retrospective study analyzed all spontaneous notifications of serious cases of ephenidine, diphenidine and methoxphenidine abuse collected by the French Addictovigilance Network from 2012 to 2016, and classified them as proven, probable and possible...
June 29, 2018: Fundamental & Clinical Pharmacology
Geneviève Durrieu, Quentin Dardonville, Michel Clanet, Jean-Louis Montastruc
We describe one report of a cervical dysplasia in a patient receiving natalizumab for Multiple Sclerosis. Other cases were identified in the WHO's global individual case safety report (ICSR) database, Vigibase® . These data underline the importance of monitoring HPV infection in patients with MS treated by natalizumab. This article is protected by copyright. All rights reserved.
June 23, 2018: Fundamental & Clinical Pharmacology
Shahla Sohrabipour, Mohammad Reza Sharifi, Mohammadreza Sharifi, Ardeshir Talebi, Nepton Soltani
This study attempted to elucidate the possible mechanism of magnesium sulfate (MgSO4 ) administration on reducing insulin resistance in type 2 diabetic rats. Fifty Wistar rats were divided into five groups: NDC was fed the normal diet, CD received high-fat diet with 35 mg/kg of streptozotocin, CD-Mg animals received MgSO4 via drinking water, CD-Ins1, and CD-Ins2 animals treated with low or high dose of insulin. Body weight and blood glucose levels were measured weekly. Intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test, and metabolic cage assessment were performed monthly...
June 5, 2018: Fundamental & Clinical Pharmacology
Amany Abdel-Ghaffar, Hala M Ghanem, Emad K Ahmed, Olfat A Hassanin, Rawda G Mohamed
The main objective of this study was to investigate the potential protective effect of ursodeoxycholic acid (UDCA) on fructose/streptozotocin-induced diabetic cataract in rats. The diabetic model (DM) was induced through the administration of 10% fructose in drinking water for 2 weeks followed by streptozotocin injection (intraperitoneal). One week later, hyperglycemia was assisted and diabetic animals were treated with UDCA either as local eye drops (0.5% solution, four times/day) or orally (100 mg/kg b.w...
June 4, 2018: Fundamental & Clinical Pharmacology
Oguz Mutlu, Tomáš Páleníček, Nikola Pinterová, Klára Šíchová, Jiří Horáček, Kristina Holubová, Cyril Höschl, Aleš Stuchlík, Faruk Erden, Karel Valeš
The adipokinetic and red pigment-concentrating hormone (AKH/RPCH) family of peptides controls fat, carbohydrate, and protein metabolism in insects. In our previous study, we showed that AKH possesses antidepressant, anxiolytic, and analgesic effects, causes hyperlocomotion, and exerts neuroprotective effects and increased brain neurotrophic factors in mice. The aim of this study was to investigate the effects of Anax imperator AKH (Ani-AKH), Libellula auripennis AKH (Lia-AKH), and Phormia-Terra hypertrehalosemic hormone (Pht-HrTH) on MK-801-induced memory deterioration in the active allothetic place avoidance test (AAPA) and MK-801-induced sensorimotor gating deficit in the prepulse inhibition test (PPI)...
June 4, 2018: Fundamental & Clinical Pharmacology
Marwa M M Refaie, Rehab A Rifaai, Nagwa M Zenhom
Nearly all men who reach average life expectancy have prostate disease. The most common is benign prostatic hyperplasia (BPH). Peroxisome proliferator-activated receptor alpha (PPARα) had protective effect in different models, but still, there are no studies explain its role in BPH. So that we investigated the effect of fenofibrate (FEN) on induced BPH by testosterone propionate (TP) (3 mg/kg/day for 4 weeks) subcutaneous injection followed by FEN (300 mg/kg/day) was given orally for 4 weeks. We measured prostate weights changes, prostatic tissue superoxide dismutase (SOD), and malondialdehyde (MDA) levels...
June 3, 2018: Fundamental & Clinical Pharmacology
Joëlle Micallef, Julien Dupouey, Elisabeth Jouve, Romain Truillet, Bruno Lacarelle, Jacques Taillard, Agnès Daurat, Colas Authié, Olivier Blin, Olivier Rascol, Pierre Philip, Daniel Mestre
Driving experiments in real conditions are considered as a 'gold standard' to evaluate the effects of drugs on driving performance. Several constraints are difficult to manage in these conditions, so driving simulation appears as the best alternative. A preliminary comparison is crucial before being able to use driving simulation as a valid evaluation method. The aim of this study was to design a driving simulation method for assessing drug effects on driving. We used cannabis (THC) as a positive control and assessed whether THC affects driving performance in simulation conditions and whether these effects are consistent with performance in real driving conditions...
May 12, 2018: Fundamental & Clinical Pharmacology
Mostafa M Hamdy, Mohamed M Elbadr, Ahmed Barakat
Fluoxetine, a commonly prescribed antidepressant, use in nociceptive pain management represents one of the unsettled issues of fluoxetine therapeutics. By reviewing the literature about fluoxetine's possible roles in this setting, those could be solitary antinociceptive effect, enhancement of acute morphine analgesia, blocking morphine tolerance development, and blocking dependence development and associated abstinence syndrome. In this study, we examined those four alleged roles of fluoxetine. Moreover, as effective alleviation of morphine tolerance, dependence, and abstinence syndrome represents one of the most challenging medical needs, we biochemically analyzed fluoxetine effect on these phenomena...
May 12, 2018: Fundamental & Clinical Pharmacology
Iat-Lon Leong, Tien-Yao Tsai, Kar-Lok Wong, Lian-Ru Shiao, Ka-Shun Cheng, Paul Chan, Yuk-Man Leung
Valproic acid (VA) is currently used to treat epilepsy and bipolar disorder. It has also been demonstrated to promote neuroprotection and neurogenesis. Although beneficial actions of VA on brain blood vessels have also been demonstrated, the effects of VA on brain endothelial cell (EC) Ca2+ signaling are hitherto unreported. In this report, we examined the effects of VA on agonist-triggered Ca2+ signaling in mouse cortical bEND.3 EC. While VA (100 μm) did not cause an acute inhibition of ATP-triggered Ca2+ signaling, a 30-min VA treatment strongly suppressed ATP-triggered intracellular Ca2+ release; however, such treatment did not affect Ca2+ release triggered by cyclopiazonic acid, an inhibitor of SERCA Ca2+ pump, suggesting there was no reduction in Ca2+ store size...
May 12, 2018: Fundamental & Clinical Pharmacology
Lei Chen, Hongwen Cao, Chao Yu, Yigeng Feng
Lobaplatin is the third-generation platinum drug that has been shown promising antitumor activity in preclinical studies and clinical trials for multiple human cancers except prostate cancer. In this study, we investigated the role of lobaplatin on prostate cancer progression and the underlying molecular mechanism. We treated a variety of prostate cancer cell lines with different doses of lobaplatin and examined cell cycle progression, cell apoptosis, cell proliferation, and cell migration. Moreover, we also assessed the in-vivo antitumor activity of lobaplatin using xenograft mouse model...
May 7, 2018: Fundamental & Clinical Pharmacology
Johana Béné, Clémentine Rousselin, Haleh Bagheri, Thierry Vial, Sophie Gautier, Marc Lambert
Isolated arthralgia, without hemorrhagic side effect, exists and is considered as a very rare adverse drug reaction according to vitamin K antagonists' (VKAs) summary of product characteristics. Up to now, there are no literature reports of isolated, nonhemorrhagic joint complications in patients receiving VKAs. Hence, the objective of this study was to describe cases of VKA-related nonhemorrhagic joint disorders (fluindione, warfarin, and acenocoumarol) reported in the French Pharmacovigilance Database (FPVD)...
May 5, 2018: Fundamental & Clinical Pharmacology
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June 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...
June 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 three 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...
June 2018: Fundamental & Clinical Pharmacology
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