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Fundamental & Clinical Pharmacology

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https://www.readbyqxmd.com/read/27933657/analysis-of-temozolomide-resistance-in-low-grade-gliomas-by-using-a-mechanistic-mathematical-model
#1
Edouard Ollier, Pauline Mazzocco, Damien Ricard, Gentian Kaloshi, Ahmed Idbaih, Agusti Alentorn, Dimitri Psimaras, Jérôme Honnorat, Jean-Yves Delattre, Emmanuel Grenier, François Ducray, Adeline Samson
Understanding how tumours develop resistance to chemotherapy is a major issue in oncology. When treated with temozolomide (TMZ), an oral alkylating chemotherapy drug, most low-grade gliomas (LGG) show an initial volume decrease but this effect is rarely long lasting. In addition, it has been suggested that TMZ may drive tumour progression in a subset of patients as a result of acquired resistance. Using longitudinal tumour size measurements from 121 patients, the aim of the present study was to develop a semi-mechanistic mathematical model to determine whether resistance of LGG to TMZ was more likely to result from primary and/or from chemotherapy-induced acquired resistance that may contribute to tumour progression...
December 9, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27891661/synergistic-effects-of-polydatin-and-vitamin-c-in-inhibiting-cardiotoxicity-induced-by-doxorubicin-in-rats
#2
Hui-Lin Wang, Xiao-Hua Cui, Hai-Lun Yu, Rong Wu, Xu Xu, Jian-Ping Gao
The purpose of this study was to assess the synergistic effect of polydatin and vitamin C on attenuating cardiotoxicity induced by doxorubicin (DOX) in rats. Polydatin could significantly increase the activity of SOD and the heart rate, attenuate myocardial pathological damage, decrease MDA content, slightly increase arterial pressure and GSH-Px activity, reduce intervals of QRS, QT and ST, and lower FFA content. The combination of polydatin and vitamin C could significantly increase arterial pressure and heart rate, decrease QRS interval and slightly reduce ST and QT intervals, significantly attenuate myocardial pathological damage, increase the activities of GSH-Px,T-SOD, Na(+) K(+) -ATPase and Ca(2+) Mg(2+) -ATPase, and elevate PCr and ATP contents, slightly increase ADP and TAN contents and PCr/ATP, and significantly decrease the contents of MDA and FFA, when compared with those in the DOX group...
November 28, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27885727/growth-inhibitory-and-proapoptotic-effects-of-l-asparaginase-from-fusarium-culmorum-asp-87-on-human-leukemia-cells-jurkat
#3
Anil Kumar Meghavarnam, Maryam Salah, Meenakshisundaram Sreepriya, Savitha Janakiraman
The objective of this study was to evaluate the anticancer properties of L-asparaginase purified from fungal isolate Fusarium culmorum ASP-87 against human T-cell leukemia cell line (Jurkat). The growth inhibitory and proapoptotic effects of purified L-asparaginase on Jurkat cell lines were investigated by determining its influence on cell viability, colony formation, DNA fragmentation and cell cycle progression. The results revealed that purified L- asparaginase showed significant decrease in cell survival with IC50 value of 90μg/ml(9 IU/ml)...
November 25, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27885718/purinergic-receptors-new-targets-for-the-treatment-of-gout-and-fibrosis
#4
REVIEW
Thomas Gicquel, Brendan Le Daré, Elisabeth Boichot, Vincent Lagente
Adenosine triphosphate is involved in many metabolic reactions, but it has also a role as a cellular danger signal transmitted through purinergic receptors (PRs). Indeed, ATP can bind to PRs which are found in the membrane of many cell types, although the relative proportions of the receptor subtypes differ. PRs are classified according to genetic and pharmacological criteria and especially their affinities for agonists and their transduction mechanism (i.e. as metabotropic P2YRs or ionotropic P2XRs). Extracellular ATP release by activated or necrotic cells may activate various PRs and especially P2X7R, the best-characterized PR, on immune cells...
November 25, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27873354/gastroprotective-effect-of-esculin-on-ethanol-induced-gastric-lesion-in-mice
#5
Weifeng Li, Yu Wang, Xiumei Wang, Hailin Zhang, Zehong He, Wenbing Zhi, Fang Liu, Xiaofeng Niu
The gastroprotective effect of esculin was investigated in a mouse model of ethanol-induced gastric lesion. Administration of esculin at doses of 5, 10, and 20 mg/kg body weight prior to ethanol ingestion led to significant gastroprotection compared to untreated mice. Gastric mucosal lesions were evaluated by macroscopic and histopathological alterations, lesion index, and myeloperoxidase (MPO) activity. Pretreatment with esculin significantly reduced macroscopic and histopathological damage, gastric lesion index, and MPO activity in a dose-dependent manner...
November 22, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27862304/hypertension-and-pregnancy-expert-consensus-statement-from-the-french-society-of-hypertension-an-affiliate-of-the-french-society-of-cardiology
#6
Claire Mounier-Vehier, Jacques Amar, Jean-Marc Boivin, Thierry Denolle, Jean-Pierre Fauvel, Geneviève Plu-Bureau, Vassilis Tsatsaris, Jacques Blacher
High blood pressure in pregnancy remains, by its complications, the leading cause of morbidity as well as maternal and fetal mortality. The frequency (5 to 10% of pregnancies) and the potential severity of this disease, both for mother and child, encourage to standardize and to optimize our medical practices. If the short-term complications for the mother and child are well known, long-term ones for the mother are beginning to be better identified. The onset of hypertension during pregnancy disrupts the classic organization of healthcare and requires the intervention of the general practitioner and/or an obstetrician, a gynecologist, a midwife, a cardiologist, a nephrologist...
November 14, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27862262/different-effects-of-selective-%C3%AE-1-adrenoceptor-antagonists-nebivolol-or-atenolol-in-acetaminophen-induced-heptatotoxicity-of-rats
#7
Remon R Rofaeil, Maha Yehia Kamel, Walaa Yehia Abdelzaher
Acetaminophen (APAP) overdose is a common cause of acute liver failure and beta blockers are commonly used drugs in clinical practice. This study aims to evaluate the effect of two different beta blockers agents as nebivolol and atenolol against APAP-induced hepatotoxicity. Male wistar rats were treated with APAP (2 g/kg/day, p.o.) to induce hepatotoxicity. Our results showed that nebivolol and atenolol reduced heart rate and blood pressure. Nebivolol (5 mg/kg /day, p.o.) for 14 days has a hepatoprotective effect shown by significant decrease in hepatic injury parameters (serum AST and ALT) with significant suppression of hepatic malondialdehyde (MDA) and nitric oxide (NO) which were elevated with APAP administration...
November 14, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27862243/antidepressant-adherence-patterns-in-older-patients-use-of-a-clustering-method-on-a-prescription-database
#8
David Braunstein, Amélie Hardy, Quentin Boucherie, Elisabeth Frauger, Olivier Blin, Gaétan Gentile, Joëlle Micallef
According to the World Health Organization, depression will become the second most important cause of disability worldwide by 2020. Our objective was to identify patterns of adherence to antidepressant treatments in older patients using several indicators of adherence and to characterize these patterns in term of medication exposure. We conducted a retrospective cohort study using the French National Health Insurance reimbursement database. Incident antidepressant users aged more than 65 were included from July 1, 2010 to June 30, 2011 and followed-up for 18 months...
November 14, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27753125/ghrelin-ameliorates-atherosclerosis-by-inhibiting-endoplasmic-reticulum-stress
#9
Wenting Ai, Min Wu, Lin Chen, Baozhou Jiang, Mian Mu, Lihua Liu, Zuyi Yuan
The effects of ghrelin, a peptide hormone, on atherogenesis are mainly beneficial. This study aimed to investigate whether ghrelin ameliorates atherosclerosis (AS) by preventing endoplasmic reticulum stress (ERS). AS was induced by a high-fat diet in ApoE(-/-) mice. AS lesions in aortas were detected by Oil-red O staining, and the inner diameter and intima-media thickness (IMT) of the abdominal aorta were analyzed by ultrasonography. The protein expression of the ERS markers 78-kDa glucose-regulated protein, C/EBP homologous protein, and active caspase-12 was detected by western blot analysis...
October 18, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27739173/possible-involvements-of-glutamate-and-adrenergic-receptors-on-acute-toxicity-of-methylphenidate-in-isolated-hippocampus-and-cerebral-cortex-of-adult-rats
#10
Majid Motaghinejad, Manijeh Motevalian, Behnaz Shabab
Neurodegeneration induced by methylphenidate (MPH), as a central stimulant with unknown long-term consequences, in adult rats' brain and the possible mechanisms involved were studied. Rats were acutely treated with MPH in presence and absence of some receptor antagonists such as ketamine, topiramate, yohimibine and haloperidol. Motor activity and anxiety level in rats were monitored. Anti-oxidant and inflammatory parameters were also measured in isolated hippocampus and cerebral cortex. MPH treated groups (10 and 20 mg/kg) demonstrated anxiety-like behavior and increased motor activity...
October 14, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27739140/complementarity-of-in-vitro-and-in-vivo-models-for-the-evaluation-of-gastro-protective-effects-of-pharmacological-substances
#11
Sonia Goineau, Vincent Castagné
Gastric mucosa is frequently exposed to various gastric irritants and there is a continuing requirement to develop new gastro-protective agents. The present study compares the effects of three such agents, sucralfate, rebamipide and cimetidine in both in vivo and in vitro indomethacin-induced gastric damage models. For the in vivo approach, rats were orally administered sucralfate, rebamipide and cimetidine at 300 mg/kg before an acute dose of indomethacin (30 mg/kg). Gastric lesions were then macroscopically examined...
October 14, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27739093/sb-334867-an-orexin-receptor-1-antagonist-decreased-seizure-and-anxiety-in-pentylenetetrazol-kindled-rats
#12
Elham Kordijaz, Ali Moghimi, Masoud Fereidoni, Saeedeh Asadi, Ali Shamsizadeh, Ali Roohbakhsh
Convulsive seizures are due to abnormal synchronous and repetitive neuronal discharges in the central nervous system (CNS). Finding new therapeutics to overcome the side effects of the current drug therapies and to increase their effectiveness is ongoing. Orexin-A and orexin-B are brain neuropeptides originating from postero-lateral hypothalamic neurons. Studies show that orexins, through activation of OX1 and OX2 receptors, have excitatory effects in the CNS. Accordingly, the present study was designed to evaluate the effect of OX1 receptor antagonist (SB-334867) on seizure- and anxiety-related behaviors of pentylenetetrazol (PTZ) kindled rats...
October 14, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27736027/drug-induced-progressive-multifocal-leukoencephalopathy-a-case-noncase-study-in-the-french-pharmacovigilance-database
#13
Olivier Colin, Sylvie Favrelière, Alexandre Quillet, Jean-Philippe Neau, Jean-Luc Houeto, Claire Lafay-Chebassier, Marie-Christine Pérault-Pochat
Progressive multifocal leukoencephalopathy (PML) is an often fatal demyelinating disease of the central nervous system. As effective treatment is unavailable, identification of all drugs that could be associated with PML is essential. The objective of this study was to investigate the putative association of reports of PML and drugs. We used the case/noncase method in the French PharmacoVigilance Database (FPVD). Cases were reports of PML in the FPVD between January 2008 and December 2015. Noncases were all other reports during the same period...
October 13, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27689348/neither-nefopam-nor-acetaminophen-can-be-used-as-post-operative-analgesics-in-a-rat-model-of-ischemic-stroke
#14
Maud Pétrault, Sophie Gautier, Vincent Bérézowski, Thavarak Ouk, Michèle Bastide, Olivier Pétrault, Régis Bordet
Analgesics such as opioid agonists are usually not given during the post-operative phase of experimental stroke because they are susceptible to interfere with the evaluation of neuroprotective therapies. Here we investigate the potential of acetaminophen and nefopam, two non-opioid analgesic drugs, to exert an analgesic effect without inducing neuroprotection in a murine model of ischemic stroke. We demonstrate that acetaminophen (200 mg/kg, PO) induces a significant decrease in the infarct volume, particularly in the cortex (VEHICLE: 200...
September 30, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27664801/is-the-unbound-concentration-of-atazanavir-of-interest-in-therapeutic-drug-monitoring
#15
David Metsu, Patrick Seraissol, Pierre Delobel, Christel Cinq-Frais, Lise Cuzin, Jacques Izopet, Etienne Chatelut, Peggy Gandia
To date, therapeutic drug monitoring (TDM) is carried out with anti-retrovirals and is usually based on total concentrations (Ct). However, for some patients, TDM does not reflect efficacy or the avoidance of toxicity as is the case for atazanavir (ATV), a HIV protease inhibitor. As the unbound concentration (Cu) is the pharmacological active form, the aim of the study was to evaluate the value of Cu and the unbound fraction (fu, fu = Cu / Ct) for the TDM of ATV. The variability of Cu and the corresponding fu of ATV were explored in 43 patients treated with ATV for an average of 13...
September 24, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27616018/nanoliposome-containing-cyclosporin-a-reduced-neuroinflammation-responses-and-improved-neurological-activities-in-cerebral-ischemia-reperfusion-in-rat
#16
Alireza Partoazar, Sanaz Nasoohi, Sayed Mehdi Rezayat, Kambiz Gilani, Shahram Ejtemaei Mehr, Amir Amani, Nastaran Rahimi, Ahmad Reza Dehpour
Cyclosporin A (CsA) is known as a neuroprotective agent against cerebral ischemia/reperfusion (I/R) in animal models. However, the significant therapeutic effects of CsA have been observed in high systemic doses or manipulating the blood brain barrier (BBB), resulting in systemic side effects and toxicity. Since the liposome nanocarries have been developed for efficient delivery of peptide and proteins, liposomal CsA (Lipo-CsA) could improve cerebral (I/R) injuries. In this study, the liposomal CsA formulation (CsA at dose of 2...
September 12, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27473285/pharmacokinetics-safety-and-tolerability-of-ceftolozane-tazobactam-in-healthy-japanese-chinese-and-white-subjects
#17
Anthony Aiudi, Benjamin Miller, Gopal Krishna, Adedayo Adedoyin, Alan Xiao
Ceftolozane/tazobactam, a novel antibacterial with potent activity against Gram-negative pathogens, was developed for treatment of complicated urinary tract infections, including pyelonephritis, and intra-abdominal infections. A phase 1 pharmacokinetic (PK) study of ceftolozane/tazobactam in healthy Japanese, Chinese, and white volunteers was conducted to assess the potential effect of ethnicity on PK. The PK of ceftolozane, tazobactam, and tazobactam metabolite M1 was compared after single 1.5- and 3-g intravenous doses of ceftolozane/tazobactam...
December 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27473027/erythropoietin-attenuates-motor-impairments-induced-by-bilateral-renal-ischemia-reperfusion-in-rats
#18
Mahshid Tahamtan, Seyed M S Moosavi, Vahid Sheibani, Mohsen Nayebpour, Saeed Esmaeili-Mahani, Mohammad Shabani
Neurologic sequelae remain a common and destructive problem in patients with acute kidney injury. The objective of this study was to evaluate the possible neuroprotective effect of erythropoietin (EPO) on motor impairments following bilateral renal ischemia (BRI) in two time points after reperfusion: short term (24 h) and long term (1 week). Male Wistar rats underwent BRI or sham surgery. EPO or saline administration was performed 30 min before surgery (1000 U/kg, i.p.). Explorative behaviors and motor function of the rats were evaluated by open field, rotarod, and wire grip tests...
December 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27469984/dihydromyricetin-enhances-the-osteogenic-differentiation-of-human-bone-marrow-mesenchymal-stem-cells-in-vitro-partially-via-the-activation-of-wnt-%C3%AE-catenin-signaling-pathway
#19
Wei Zhang, Shengdong Wang, Houfa Yin, Erman Chen, Deting Xue, Qiang Zheng, Xiang Gao, Zhijun Pan
Substantial evidence has demonstrated that the decreased osteogenic differentiation of bone mesenchymal stem cells (BMSCs) is closely related to bone metabolic diseases. Thus, it is very important to develop several potentially useful therapeutic agents to enhance BMSC osteogenesis. Flavonoids show promise in enhancing bone mass. Dihydromyricetin (DMY), a type of flavonoid, has not yet been investigated regarding its effects on BMSC osteogenesis. To investigate the effects of DMY on osteogenesis, human BMSCs were induced with or without DMY...
December 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27421789/effect-of-subacute-agomelatine-treatment-on-painful-diabetic-neuropathy-involvement-of-catecholaminergic-mechanisms
#20
Taliha H Aydın, Özgür D Can, Ümide Demir Özkay, Nazlı Turan
In this study, we investigated the effects of subacute agomelatine (40 and 80 mg/kg) administration on chronic hyperglycemia, metabolic parameters, and pain perception in streptozotocin-induced diabetic rats. Fasting blood glucose measurements and oral glucose tolerance tests were performed to evaluate the effect of agomelatine on glycemia, while metabolic parameters were monitored using metabolic cages. Potential effect of agomelatine on diabetes-induced mechanical and thermal allodynia was evaluated using dynamic plantar aesthesiometer and warm plate (38 °C) tests, respectively...
December 2016: Fundamental & Clinical Pharmacology
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