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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 non-selective NSAIDs versus placebo, and a lower gastrointestinal risk of coxibs versus non-selective 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 non-exposed. 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 non-exposed 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
Charanraj Goud Alladi, Ravi Philip RajKumar, Surendiran Adithan, Cynthia Marie-Claire, Frank Bellivier, Deepak Gopal Shewade
Treatment response to antipsychotic drugs is variable and conflicting results have been obtained while studying the influence of DRD2 and HTR2 genetic variants on antipsychotic drug efficacy. To explore further, the present study aimed to assess the influence of DRD2 -141 C Ins/Del, Taq1A and HTR2A -1438 G/A, 102T/C and HTR2C -759 C/T genetic polymorphisms in response to risperidone in patients with schizophrenia. The study was conducted among the n=320 South Indian patients with schizophrenia who received risperidone treatment (4-8 mg per day) for a minimum of four weeks...
October 17, 2018: Fundamental & Clinical Pharmacology
Krzysztof Łukawski, Grzegorz Raszewski, Stanisław J Czuczwar
It has been demonstrated that certain angiotensin-converting enzyme (ACE) inhibitors and angiotensin AT1 receptor antagonists can possess anticonvulsant activity. The purpose of the current study was to examine the effect of aliskiren, a direct renin inhibitor and a novel antihypertensive drug, against pentylenetetrazole (PTZ)-induced clonic seizures in mice and on the protective activity of conventional antiepileptic drugs (AEDs) in this seizure model. Effects of aliskiren on the PTZ threshold and the protective efficacy of AEDs such as clonazepam (CLO), phenobarbital (PB), valproate (VPA) and ethosuximide (ETX) in the PTZ test, were evaluated in adult Swiss mice...
October 12, 2018: Fundamental & Clinical Pharmacology
Julie Garon-Czmil, Nadine Petitpain, Franck Rouby, Marion Sassier, Samy Babai, Mélissa Yelehe-Okouma, Georges Weryha, Marc Klein, Pierre Gillet
Immunotherapy with immune checkpoint inhibitors (ICIs) for cancer has become increasingly prescribed in recent years. Indeed, it is used to treat both solid and hematological malignancies due to their considerable potential in treating melanoma, non-small cell lung and other cancers. Immune-mediated related adverse endocrine toxicity, and especially thyroiditis, are seen as a growing problem needing specific screening and management. This study aims at describing thyroid dysfunctions induced by the ICIs marketed in France, which are registered in the French Pharmacovigilance database...
October 11, 2018: Fundamental & Clinical Pharmacology
Elodie Gautier-Veyret, Aurélie Truffot, Sébastien Bailly, Xavier Fonrose, Anne Thiebaut-Bertrand, Julia Tonini, Jean-Yves Cahn, Françoise Stanke-Labesque
Voriconazole (VRC) overdoses are frequent and expose patients at high risk of adverse effects. This case-control study performed in hematological patients who benefited from VRC therapeutic drug monitoring from January 2012 to December 2015 aimed to identify risk factors of VRC overdose. Pharmacogenetic, biological, and demographic parameters at the time of VRC trough concentration (Cmin) were retrospectively collected from medical records. Cases (VRC overdose: defined by a VRC Cmin ≥ 4 mg/L; n = 31) were compared to controls (no VRC overdose: defined by VRC Cmin < 4 mg/L; n = 31) using non-parametric or Chi-square tests followed by multivariable analysis...
October 10, 2018: Fundamental & Clinical Pharmacology
Delphine Lauzeille, Marylène Guerlais, Claire Sallenave-Namont, François Etcheverrigaray, Luciano Broccato, Quentin Poisblaud, Pascale Jolliet, Caroline Victorri-Vigneau
The principal outcome was to identify which hypnotics substances, medicated (Benzodiazepines, antihistamine, antidepressant…) or not medicated (herbal medicine, homeopathy, melatonin…), were consumed by community pharmacy patients who reported taking something for sleep disorder, and which factors can influence the consumption of medicated substance rather than non-medicated substance. Data was collected via a network of 73 partner pharmacies around Nantes, France. Patients who reported taking a substance to sleep completed a questionnaire that collected data relative to the different substances consumed by that person for sleep, and the desired effect...
October 5, 2018: Fundamental & Clinical Pharmacology
Thierry Vial, Henry Bailly, Marie-Christine Perault-Pochat, Anne Default, Charlène Boulay, Laurent Chouchana, Behrouz Kassai
The objectives of this study were to describe the characteristics and natural history of beta-lactam-induced severe neutropaenia and to evaluate the risk of recurrences after another beta-lactam readministration. Reports of pure agranulocytosis associated with a beta-lactam exposure within the 10 days preceding the neutropaenia were extracted from the French Pharmacovigilance Database over the year 2010. Cases with another evident cause or more likely attributable to another drug were excluded. Data were analyzed for demographics, clinical and biological features, prognosis factors, granulocyte colony stimulating factors administration and outcome...
October 5, 2018: Fundamental & Clinical Pharmacology
Justyna Niderla-Bielińska, Krzysztof Bartkowiak, Bogdan Ciszek, Ewa Jankowska-Steifer, Alicja Krejner, Anna Ratajska
Sulodexide (SDX) is a mixed drug containing low-molecular-weight heparin sulfate and dermatan sulfate. It exerts mild anticoagulant action but can also affect leukocytes, macrophages, and cell-cell adhesion and may interact with growth factors although its direct influence on endothelial cells is not well described. Clinically, SDX is used for the treatment of cardiovascular diseases, where it exerts anti-inflammatory and endothelial protective effects. The aim of this study was to determine the influence of SDX on tubule formation and angiogenesis-related proteins' mRNA expression in endothelial cell line C166 and mouse proepicardial explants...
September 24, 2018: Fundamental & Clinical Pharmacology
Stefânia E Santos, Fernanda P R A Ribeiro, Pedro M N Menezes, Luiz A M Duarte-Filho, Jullyana S S Quintans, Lucindo J Quintans-Junior, Fabricio S Silva, Luciano A A Ribeiro
The monoterpene alcohol (-)-borneol has many biological effects such as sedative, anti-inflammatory, analgesic, anti-nociceptive, antithrombotic and vasorelaxant effects. Our objective in this study was to investigate the mechanism of action of (-)-borneol and determine its vasorelaxant effect. (-)-Borneol was tested on isolated aortic rings contracted with PE (10-6 M). This study was performed in the absence or in the presence of endothelium, L-NAME (100 μM), indomethacin (10 μM), TEA (1 and 10 mM), 4-AP (1 mM), or glibenclamide (1 mM) to assess the participation of EDRF, nitric oxide, prostanoids and potassium channels on the relaxing effect of (-)-borneol...
September 21, 2018: Fundamental & Clinical Pharmacology
Cícero Francisco Bezerra Felipe, Aline Mirely Sousa Albuquerque, João Luis Xavier de Pontes, José Ítalo Vieira de Melo, Teresa Carolliny Moreira Lustoza Rodrigues, Ada Mirtes Pereira de Sousa, Álefe Brito Monteiro, Ana Elisa da Silva Ribeiro, Janice Pereira Lopes, Irwin Rose Alencar de Menezes, Reinaldo Nóbrega de Almeida
Convulsions occur in response to a loss of balance between excitatory and inhibitory neurotransmitters, and the treatment for this condition consists in restore such lost balance. Many anticonvulsant drugs present side effects which may limit their use. This fact has stimulated the search for new sources of treatment from aromatic plants. Many monoterpenes commonly present in essential oils are known because of their anticonvulsant properties. The anticonvulsant effect of α- and β-pinene, two structural isomers, is still little studied...
September 19, 2018: Fundamental & Clinical Pharmacology
Mete Ozcan, Sinan Canpolat, Ozgur Bulmus, Nazife Ulker, Ahmet Tektemur, Suat Tekin, Sibel Ozcan, Ihsan Serhatlioglu, Emine Kacar, Ahmet Ayar, Haluk Kelestimur
The main objective of this study was to investigate potential effectiveness of agomelatine pre-treatment in prevention of diabetes itself and encephalopathy, with a focus on brain tissue oxidative stress and inflammatory processes in streptozotocin (STZ)-induced diabetic mice. Interleukine-1β (IL-1β) and TACR1 (NK1), which is a tachykinine receptor, were used for the investigation of inflammation in the brain regions including raphe nuclues, periaqueduqtal gyrus (PAG), amygdala and nucleus accumbens. The effects of agomelatine on total antioxidant capacity were also evaluated...
September 14, 2018: Fundamental & Clinical Pharmacology
Zhike Zhou, Jun Hou, Juanjuan Xiong, Min Li
Sulfuretin is a major flavonoid found in Rhus verniciflua and carries anti-oxidative and anti-inflammatory properties, but its potential use in the control of skin pigmentation is unknown. The purpose of the present study was to elucidate sulfuretin as a new active compound inhibiting melanogenesis and the underlying mechanism. The effects of sulfuretin on melanin production, tyrosinase activity, cAMP level, and MITF expression were examined in murine melanoma B16 cells challenged with forskolin or α-MSH. The inhibitory effect of sulfuretin on melanogenesis was further validated on neonatal human melanocytes...
September 14, 2018: Fundamental & Clinical Pharmacology
Nataša Ristić, Nataša Nestorović, Milica Manojlović-Stojanoski, Svetlana Trifunović, Vladimir Ajdžanović, Branko Filipović, Lazo Pendovski, Verica Milošević
Dexamethasone (Dx) is often used in obstetric practice to promote fetal lung maturation and to prevent respiratory distress syndrome when the risk of preterm delivery persists. This therapy enables survival of the newborn, but also is associated with deleterious effects on the offspring, such as reproductive disorders. The aim of this study was to determine specifically whether prenatal exposure to Dx disturbs the physiological balance between proliferation and apoptosis of germinative cells (GC) in the ovary of 19 and 21 day old fetuses and thus induces developmental programing of the female reproductive system...
September 14, 2018: Fundamental & Clinical Pharmacology
Camille Tron, Marie Allard, Antoine Petitcollin, Marie-José Ferrand-Sorre, Marie-Clémence Verdier, Julie Querzerho-Raguideau, Benoit Blanchet, Jérôme Le Priol, Mickael Roussel, Yves Deugnier, Eric Bellissant, Florian Lemaitre
Measuring tacrolimus (TAC) concentration in peripheral blood mononuclear cells (PBMC) could better reflect the drug effect on its target (calcineurin (CaN) in lymphocytes) than whole blood concentrations. Mechanisms influencing TAC diffusion into PBMC are not well characterized. This work aimed at describing, ex-vivo, TAC diffusion kinetics into PBMC and investigating the contribution of membrane transporters to regulate TAC intracellular concentration as well as the impact on CaN activity. PBMC were incubated with TAC for 5 min to 4h and under several experimental conditions: 37°C (physiological conditions) 4°C (inhibition of influx and efflux active transport), 37°C + transporter inhibitors (verapamil, carvedilol, probenecid, bromosulphophtalein respectively inhibitors of P-gp, OAT, OATP)...
September 11, 2018: Fundamental & Clinical Pharmacology
Ayat Kaeidi, Zahra Hajializadeh, Farank Jahandari, Iman Fatemi
One of the main pathological mechanisms of neurotoxicity in diabetic situation is oxidative stress promoted by hyperglycemia. It has been shown that leptin has neuroprotective effects and may provide neuronal survival signals. This study was designed to reveal the possible neuroprotective effects of leptin in hyperglycemic conditions. Pheochromocytoma (PC12) cell viability was assessed via the MTT test. Cellular reactive oxygen species (ROS) generation was determined by DCFH-DA analysis. The malondialdehyde (MDA) and glutathione (GSH) levels were measured in high glucose-treated PC12 cells with and without leptin co-treatment...
September 11, 2018: Fundamental & Clinical Pharmacology
Adriane F Brito, Lorrane K S Moreira, Ricardo Menegatti, Elson A Costa
Medicinal chemistry is a science applied to the search and discovery of new therapeutic agents for the treatment of various diseases. Therefore, promising structures have been identified; one of these structures is the piperazine moiety, a cyclic molecule containing two nitrogen atoms in positions 1 and 4 as well as four carbon atoms. Many piperazine derivatives have central pharmacological activity that mainly involves the activation of the monoamine pathway. Thus, piperazine derivatives have been the subject of research for many central therapeutic applications, including antipsychotic, antidepressant, and anxiolytic applications...
August 27, 2018: Fundamental & Clinical Pharmacology
Alecsander F Bressan, Gisele A Fonseca, Rita C Tostes, R Clinton Webb, Victor Vitorino Lima, Fernanda Regina Giachini
The activation of extracellular signal-regulated kinase 1 and 2 (ERK 1/2) pathway promotes increased vascular contractility in angiotensin II (Ang II)-induced hypertensive mice. Interleukin-10 (IL-10) is an immune-regulatory cytokine with the ability to prevent vascular hypercontractility during hypertension. We hypothesized that IL-10 would downregulate vascular ERK 1/2 activation during Ang II-induced hypertension. Wild-type (WT) or IL-10 knockout (IL-10-/- ) mice received Ang II infusion (90 ηg.min) or vehicle (saline), via osmotic mini-pumps (0...
August 24, 2018: Fundamental & Clinical Pharmacology
Matthias D Hofer
No abstract text is available yet for this article.
October 2018: Fundamental & Clinical Pharmacology
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