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Fundamental & Clinical Pharmacology

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https://www.readbyqxmd.com/read/28078787/targeting-nasopharyngeal-carcinoma-by-artesunate-through-inhibiting-akt-mtor-and-inducing-oxidative-stress
#1
Qin Li, Wei Ni, Zhifeng Deng, Minghe Liu, Lazhi She, Qiong Xie
Drug repurposing has become an alternative therapeutic strategy for cancer treatment given the known pharmacokinetics and toxicity. The inhibitory effects of artesunate have been reported in various cancers. In this work, we investigated the effects of artesunate in nasopharyngeal carcinoma (NPC). We demonstrate that artesunate significantly inhibits proliferation via arresting NPC cells at G2/M phase. It also induces apoptosis through caspase-dependent and mitochondria-independent pathways in multiple NPC cell lines...
January 11, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28078759/bufalin-a-bufanolide-steroid-from-the-parotoid-glands-of-the-chinese-toad-inhibits-l-type-ca-2-channels-and-contractility-in-rat-ventricular-myocytes
#2
Tao Song, Xi Chu, Xuan Zhang, Qiong Tao Song, Ying Zhang, Yuanyuan Zhang, Xue Han, Jianping Zhang, Li Chu
Bufalin is a bufanolide steroid compound in Chan Su. Chan Su is a traditional Chinese medicine prepared from the dried white secretion of the auricular and skin glands of toads, and has been used as an Oriental drug. However, the effect of bufalin on cardiac function and its underlying cellular mechanisms remain unclear. Here, we explore the cellular mechanisms of bufalin on myocardial protection via the whole-cell patch-clamp recording and video-based edge detection system. Exposure to bufalin resulted in a concentrated-dependent blockade of ICa-L , with the half-maximal inhibitory concentration (IC50 ) of 60 μM and the maximal inhibitory effect of 71...
January 11, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28036112/protocol-of-glucose-control-safety-and-efficacy-in-type-2-diabetes-a-network-meta-analysis-glucose-dinet-protocol-rational-and-design
#3
REVIEW
Guillaume Grenet, Audrey Lajoinie, Shams Ribault, Gia Bao Nguyen, Thomas Linet, Augustin Metge, Catherine Cornu, Michel Cucherat, Philippe Moulin, François Gueyffier
The aim of this study is to propose a ranking of the currently available antidiabetic drugs, regarding vascular clinical outcomes, in type 2 diabetic patients, through a network meta-analysis approach. Randomized clinical trials, regardless of the blinding design, testing contemporary antidiabetic drugs and considering clinically relevant outcomes in patients with type 2 diabetes mellitus will be included. The primary outcomes of this analysis will be overall mortality, cardiovascular mortality, and major cardiovascular events...
December 30, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28036099/can-drugs-induce-or-aggravate-sleep-apneas-a-case-non-case-study-in-vigibase-%C3%A2-the-who-pharmacovigilance-database
#4
Mélanie Linselle, Agnès Sommet, Emmanuelle Bondon-Guitton, Florence Moulis, Geneviève Durrieu, Justine Benevent, Vanessa Rousseau, Leila Chebane, Haleh Bagheri, François Montastruc, Jean-Louis Montastruc
The potential favorising role of drugs in Sleep Apnea Syndrome (SAS) is unknown. The present study investigates drugs associated with SAS in a pharmacovigilance database. SAS recorded as Adverse Drug Reactions (ADRs) in Vigibase(®) , the WHO pharmacovigilance database (more than 11 million reports), from 1978 to 2015 were selected. The risk of SAS reports was estimated using the case non-case method, with cases being SAS and non-cases all other recorded ADRs. During this 37-year period, 3,325 ADRs including the word SAS were registered (0...
December 30, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28012206/uptake-and-efflux-kinetics-and-intracellular-activity-of-voriconazole-against-a-fumigatus-in-human-pulmonary-epithelial-cells-a-new-application-for-the-prophylaxis-and-early-treatment-of-invasive-pulmonary-aspergillosis
#5
Taotao Wang, Qianting Yang, Lu Chen, Ying Li, Ti Meng, Yan Wang, Tao Zhang, Jin'e Lei, Jianfeng Xing, Yalin Dong
Invasive pulmonary aspergillosis (IPA), most caused by A. fumigatus, is a serious life-threating infection in immunocompromised patients. Voriconazole is used to prevent and treat IPA. However, little is known about the pharmacological characteristics of voriconazole in pulmonary epithelial cells, which are the target site for the prophylaxis and early treatment of IPA. The aim of the study was to evaluate the kinetics and activity of voriconazole against A. fumigatus in A549 cells. High-performance liquid chromatography/tandem mass spectrometry and time-kill method was used to study the cellular pharmacokinetic and pharmacodynamics of voriconazole...
December 23, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27998000/severe-excessive-daytime-sleepiness-induced-by-hydroxyurea
#6
Bruno RevoL, Marie Joyeux-Faure, Marie-Victoire Albahary, Remy Gressin, Michel Mallaret, Jean-Louis Pepin, Sandrine H Launois
Excessive daytime sleepiness (EDS) has been reported with many drugs, either as an extension of a hypnotic effect (e.g., central nervous system depressants) or as an idiosyncratic response of the patient. Here, we report unexpected and severe subjective and objective EDS induced by hydroxyurea therapy, with a favorable outcome after withdrawal. Clinical history, sleep log, polysomnography and multiple sleep latency tests confirming the absence of other EDS causes are presented. This article is protected by copyright...
December 20, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27992964/pkr-signalling-and-paradigms-of-cardiometabolic-syndrome
#7
REVIEW
Jaspreet Kalra, Arti Dhar
Metabolic syndrome (Met S) is a collection of the most severe cardio-metabolic risk factors that encompasses raised fasting plasma glucose, dyslipidemia, insulin resistance, obesity and hypertension. The precise mechanism underlying the pathogenesis of Met S remains unclear. More often oxidative stress, inflammation and apoptosis are implicated in its etiology. Recently, double stranded RNA dependent protein kinase has been found to intersect at the crossroad of oxidative stress, inflammation and apoptosis in several metabolic diseases...
December 19, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27933657/analysis-of-temozolomide-resistance-in-low-grade-gliomas-by-using-a-mechanistic-mathematical-model
#8
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
#9
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
#10
Anil K 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 90 μg/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
#11
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, adenosine 5'-triphosphate (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)...
November 25, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27873354/gastroprotective-effect-of-esculin-on-ethanol-induced-gastric-lesion-in-mice
#12
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
#13
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 (5-10% of pregnancies) and the potential severity of this disease, for both 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 health care 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
#14
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
#15
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/27473285/pharmacokinetics-safety-and-tolerability-of-ceftolozane-tazobactam-in-healthy-japanese-chinese-and-white-subjects
#16
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
#17
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
#18
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
#19
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
https://www.readbyqxmd.com/read/27416488/hibiscus-sabdariffa-increases-hydroxocobalamin-oral-bioavailability-and-clinical-efficacy-in-vitamin-b12-deficiency-with-neurological-symptoms
#20
Zouhayr Souirti, Mouna Loukili, Imar D Soudy, Kaies Rtibi, Aslihan Özel, Nicolas Limas-Nzouzi, Seloua El Ouezzani, Bruno Eto
The aim of the study was to evaluate the bioavailability and clinical benefits of oral new formulation (HB12 ) of hydroxocobalamin (Hdrx) with Hibiscus sabdariffa (HS). First, in an observational study, a cohort of 30 vitamin B12 -deficient patients (vit B12 < 200 pg/mL) with neurological symptoms received oral fixed dose of Hdrx containing 15 mg Hdrx daily for 10 days followed by 15 mg monthly. Clinical benefits were evaluated on haematological and biochemical parameters, and neurological improvement at days 10 and 90 compared to day 0...
December 2016: Fundamental & Clinical Pharmacology
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