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European Journal of Pharmacology

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https://www.readbyqxmd.com/read/29679542/treatments-for-diabetes-mellitus-type-ii-new-perspectives-regarding-the-possible-role-of-calcium-and-camp-interaction
#1
REVIEW
Diego Soares Carvalho, Alexandre Aparecido de Almeida, Aurélio Ferreira Borges, Diego Vannucci Campos
Diabetes mellitus (DM) is among the top ten causes of death worldwide. It is considered to be one of the major global epidemics of the 21st century, with a significant impact on public health budgets. DM is a metabolic disorder with multiple etiologies. Its pathophysiology is marked by dysfunction of pancreatic β-cells which compromises the synthesis and secretion of insulin along with resistance to insulin action in peripheral tissues (muscle and adipose). Subjects presenting insulin resistance in DM type 2 often also exhibit increased insulin secretion and hyperinsulinemia...
April 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29679541/treatment-with-d-%C3%AE-hydroxybutyrate-protects-heart-from-ischemia-reperfusion-injury-in-mice
#2
Yongsheng Yu, Yunhua Yu, Yuefan Zhang, Zhigang Zhang, Weishuai An, Xianxian Zhao
The present study was designed to examine the protection of D-β-hydroxybutyrate (BHB) against ischemia/reperfusion (I/R) injury in heart and investigate its underlying mechanism. Male adult mice were exposed to 30min of ischemia and 24h of reperfusion. Osmotic pumps were implanted subcutaneously 5min before reperfusion for continuous delivery of the exogenous BHB (1.6mmol/kg/24h). Treatment with BHB reduced infarct size and levels of cardiac troponin I, creatine kinase and lactate dehydrogenase in serum, attenuated apoptosis in myocardium, and preserved cardiac function of I/R mice...
April 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29678719/carnosic-acid-attenuates-cartilage-degeneration-through-induction-of-heme-oxygenase-1-in-human-articular-chondrocytes
#3
Hiroyuki Ishitobi, Yohei Sanada, Yoshio Kato, Yasunari Ikuta, Sachi Shibata, Satoshi Yamasaki, Martin K Lotz, Kiminori Matsubara, Shigeru Miyaki, Nobuo Adachi
Osteoarthritis (OA) is common age-associated disease, and associated with joint pain, mobility limitations and compromised overall quality of life. OA treatment is currently limited to pain management and joint arthroplasty at end stage disease. Oxidative damage to cartilage extracellular matrix and cells is an important mechanism in joint aging and OA pathogenesis. Evidence from in vitro and in vivo models of OA suggests that pharmaceuticals and natural compounds with antioxidant properties reduce expression of mediators of OA pathogenesis and OA severity in animal models...
April 17, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29673908/mechanism-underlying-the-contractile-activity-of-utp-in-the-mammalian-heart
#4
Ulrich Gergs, Daniel Rothkirch, Britt Hofmann, Hendrik Treede, Bernard Robaye, Andreas Simm, Christa E Müller, Joachim Neumann
We previously reported that uridine 5'-triphosphate (UTP), a pyrimidine nucleoside triphosphate produced a concentration- and time-dependent increase in the contraction force in isolated right atrial preparations from patients undergoing cardiac bypass surgery due to angina pectoris. The stimulation of the force of contraction was sustained rather than transient. In the present study, we tried to elucidate the underlying receptor and signal transduction for this effect of UTP. Therefore, we measured the effect of UTP on force of contraction, phosphorylation of p38 and ERK1/2, in human atrial preparations, atrial preparations from genetically modified mice, cardiomyocytes from adult mice and cardiomyocytes from neonatal rats...
April 16, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29665367/suppression-of-akt-mediated-hdac3-expression-and-cdk2-t39-phosphorylation-by-a-bichalcone-analog-contributes-to-s-phase-retardation-of-cancer-cells
#5
Kuang-Chen Hung, Meng-Liang Lin, Shih-Wei Hsu, Chuan-Chun Lee, Ren-Yu Huang, Tian-Shung Wu, Shih-Shun Chen
Targeting cell cycle regulators has been a suggested mechanism for therapeutic cancer strategies. We report here that the bichalcone analog TSWU-CD4 induces S phase arrest of human cancer cells by inhibiting the formation of cyclin A-phospho (p)-cyclin-dependent kinase 2 (CDK2, threonine [Thr] 39) complexes, independent of mutant p53 expression. Ectopic expression of CDK2 (T39E), which mimics phosphorylation of the Thr 39 residue of CDK2, partially rescues the cells from TSWU-CD4-induced S phase arrest, whereas phosphorylation-deficient CDK2 (T39A) expression regulates cell growth with significant S phase arrest and enhances TSWU-CD4-triggered S phase arrest...
April 14, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29665366/3-7-bis-2-hydroxyethyl-icaritin-a-potent-inhibitor-of-phosphodiesterase-5-prevents-monocrotaline-induced-pulmonary-arterial-hypertension-via-no-cgmp-activation-in-rats
#6
Tao-Hua Lan, Xiao-Ling Chen, Yun-Shan Wu, Hui-Liang Qiu, Jun-Zhe Li, Xin-Min Ruan, Dan-Ping Xu, Dong-Qun Lin
Pulmonary arterial hypertension (PAH) is a chronic progressive disease which leads to elevated pulmonary arterial pressure and right heart failure. 3,7-Bis(2-hydroxyethyl)icaritin (ICT), an icariin derivatives, was reported to have potent inhibitory activity on phosphodiesterase type 5 (PDE5) which plays a crucial role in the pathogenesis of PAH. The present study was designed to investigate the effects of ICT on monocrotaline (MCT)-induced PAH rat model and reveal the underlying mechanism. MCT-induced PAH rat models were established with intragastric administration of ICT (10, 20, 40mg/kg/d), Icariin (ICA) (40mg/kg/d) and Sildenafil (25mg/kg/d)...
April 14, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29665365/dehydroeffusol-inhibits-viability-and-epithelial-mesenchymal-transition-through-the-hedgehog-and-akt-mtor-signaling-pathways-in-neuroblastoma-cells
#7
Kang He, Guoqing Duan, Yanyang Li
Neuroblastoma (NB) is the most predominant extracranial solid tumor of infancy in the world. However, current chemotherapy has limited efficacy for more advanced stages of NB due to acquired chemoresistance or acute toxicity in NB patients. Therefore, effective novel anti-NB drugs are desperately needed. The present study aimed to investigate the effects of dehydroeffusol (DHE), a phenanthrene isolated from J. effuses, on NB cells and its underlying mechanism. The results showed that DHE treatment effectively inhibited NB cell viability in a dose-dependent manner...
April 14, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29665364/casticin-inhibits-pdgf-induced-proliferation-and-migration-of-airway-smooth-muscle-cells
#8
Ying Dai, Ruiduo Cheng, Jie Gao, Ying Li, Chunyan Lou, Yanyang Li
Casticin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone), one of the main components from Vitex rotundifolia L., was reported to possess several pharmacological properties, including anti-inflammatory, hepatoprotective, anticancer, anti-asthma activities. However, the effects of casticin on airway smooth muscle cells (ASMCs) proliferation and migration have not been explored. This study aimed to evaluate the effects of casticin on the proliferation and migration of ASMCs, and study the possible molecular mechanism...
April 14, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29665363/isoquercetin-ameliorates-hyperglycemia-and-regulates-key-enzymes-of-glucose-metabolism-via-insulin-signaling-pathway-in-streptozotocin-induced-diabetic-rats
#9
Muthukumaran Jayachandran, Tongze Zhang, Kumar Ganesan, Baojun Xu, Stephen Sum Man Chung
Among the foremost common flavonoids within the human diet, quercetin glycosides possess neuroprotective, cardioprotective, anti-oxidative, chemopreventive, and anti-allergic properties. Isoquercetin is one such promising candidate with anti-diabetic potential. However, complete studies of its molecular action on insulin signaling pathway and carbohydrate metabolizing enzymes remain unclear. Hence, we have designed this study to accumulate the experimental evidence in support of anti-diabetic effects of isoquercetin...
April 14, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29655978/sitagliptin-prevents-isoproterenol-induced-myocardial-infarction-in-rats-by-modulating-nitric-oxide-synthase-enzymes
#10
Mohamed Abdellah Ibrahim, Ayman Geddawy, Soha Abdel-Wahab
Ischemic heart disease is a common cause of mortality worldwide. Sitagliptin is a new anti-diabetic drug acting as dipeptidyl peptidase-4 (DPP-4) inhibitor. The study investigated the ability of sitagliptin to prevent pathological changes of isoproterenol- (ISO-) induced myocardial injury in rats. The role of nitric oxide (NO) was also reported. Rats were assorted into six groups (n = 7) and treated for 12 days. Group 1: normal control, received normal saline. Group 2, sitagliptin control, received sitagliptin (10mg/kg, orally)...
April 12, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29654783/resveratrol-attenuates-pro-inflammatory-cytokines-and-activation-of-jak1-stat3-in-btbr-t-itpr3-tf-j-autistic-mice
#11
Sheikh F Ahmad, Mushtaq A Ansari, Ahmed Nadeem, Saleh A Bakheet, Mohammad Z Alzahrani, Musaad A Alshammari, Wael A Alanazi, Abdullah F Alasmari, Sabry M Attia
Autism is a neurodevelopmental disorder characterized by qualitative impairment in communication, social interaction, and repetitive stereotypic behavior. Resveratrol plays a role in several disorders such as neuroimmune, autoimmune, and allergic disorders. BTBR T+ Itpr3tf /J (BTBR) mice, a model for autism, show several behavioral deficits that are physiological characteristics similar to those observed in patients with autism. Previous studies have shown that JAK-STAT signaling pathway is associated with many neurodevelopmental disorders...
April 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29654782/mirabegron-a-%C3%AE-3-adrenoceptor-agonist-reduced-platelet-aggregation-through-cyclic-adenosine-monophosphate-accumulation
#12
Camila Bitencourt Mendes-Silvério, Evandro Marcos Alexandre, Caroline Honaiser Lescano, Edson Antunes, Fabiola Zakia Mónica
Mirabegron is a β3 -adrenoceptor agonist and released on the marked for the treatment of overactive bladder. Because mirabegron is the only β3 -adrenoceptor agonist available and substances that increase the levels of cyclic adenosine monophosphate (cAMP) inhibit platelet activity, we tested the hypothesis that mirabegron could have antiplatelet activity. Collagen- and thrombin induced platelet aggregation, thromboxane B2 (TXB2 ) and cyclic nucleotides quantification and calcium (Ca2+ ) mobilization were determined in the absence and presence of mirabegron in human washed platelets...
April 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29654781/effects-of-propofol-on-cancer-development-and-chemotherapy-potential-mechanisms
#13
REVIEW
Sufang Jiang, Ya Liu, Lining Huang, Fuzhen Zhang, Rongtian Kang
Propofol (2, 6-diisopropylphenol) is the commonly used intravenous sedative-hypnotic agent. Accumulating evidence shows that propofol affects cancer development by direct and indirect ways. In this review, we will provide an overview of the effects of propofol on cancer development and chemotherapy, with a special focus on the underlying molecular mechanisms involved. Propofol regulates both microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), and serves as a regulator of different signaling pathways including hypoxia-inducible factor-1α (HIF-1α), mitogen-activated protein kinase (MAPK), nuclear factor-kappaB (NF-κB), and nuclear factor E2-related factor-2 (Nrf2) pathways...
April 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29653090/vascular-and-molecular-pharmacology-of-the-metabolically-stable-cgrp-analogue-sax
#14
Majid Sheykhzade, Bahareh Abdolalizadeh, Cassandra Koole, Darryl Scott Pickering, Karin Dreisig, Sara Ellinor Johansson, Balsam Kadri Abboud, Rasmus Dreier, Jais Oliver Berg, Jørgen Lykke Jeppesen, Patrick M Sexton, Lars Edvinsson, Denise Wootten, Anette Sams
The main purpose of this study was to compare in vitro pharmacological properties of human αCGRP (CGRP) and a recently discovered metabolically stable CGRP analog, SAX, in isolated rat and human artery segments. In rat, CGRP and SAX induced similar vasodilatory responses in isolated mesenteric artery with the potency of SAX being lower than that of CGRP (vasodilatory pEC50 8.2 ± 0.12 and 9.0 ± 0.11, respectively). A corresponding difference in receptor binding affinity of SAX and CGRP was determined in rat cerebral membranes (pKi 8...
April 10, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29653089/modification-of-levosimendan-induced-suppression-of-atrial-natriuretic-peptide-secretion-in-hypertrophied-rat-atria
#15
Lamei Yu, Kuichang Yuan, Byung Mun Park, Suhn Hee Kim
This study aimed to determine the effects of levosimendan, a calcium sensitizer, on atrial contractility and atrial natriuretic peptide (ANP) secretion and its modification in hypertrophied atria. Isolated perfused beating rat atria were used from control and isoproterenol-treated rats. Levosimendan and its metabolite OR-1896 caused a positive inotropic effect and suppressed ANP secretion in rat atria. Similar to levosimendan, the selective phosphodiesterase 3 (PDE3) or PDE4 inhibitor also suppressed ANP secretion...
April 10, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29627311/lysosomotropic-cationic-amphiphilic-drugs-inhibit-adipocyte-differentiation-in-3t3-l1k-cells-via-accumulation-in-cells-and-phospholipid-membranes-and-inhibition-of-autophagy
#16
Patrik Kagebeck, Violetta Nikiforova, Lars Brunken, Arrabi Easwaranathan, Joelle Ruegg, Ian Cotgreave, Vesna Munic Kos
Some cationic amphiphilic drugs (CADs) have been individually reported to interfere with the differentiation of immune system cells, such as macrophages and dendritic cells. To investigate the possible generic nature of this process, in this study we aimed to see whether these drugs are capable of interfering with the differentiation of adipocytes. Further, we investigated whether this feature might be connected to the lysosomotropic character of these drugs, and their disturbance of intracellular membrane trafficking rather than to the individual pharmacologic properties of each drug...
April 5, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29627310/understanding-antidepressant-discontinuation-syndrome-ads-through-preclinical-experimental-models
#17
REVIEW
Konstantin N Zabegalov, Tatiana O Kolesnikova, Sergey L Khatsko, Andrey D Volgin, Oleg A Yakovlev, Tamara G Amstislavskaya, Polina A Alekseeva, Darya A Meshalkina, Ashton J Friend, Wandong Bao, Konstantin A Demin, Raul R Gainetdinov, Allan V Kalueff
Antidepressant drugs are currently one of the most prescribed medications. In addition to treatment resistance and side effects of antidepressants, their clinical use is further complicated by antidepressant discontinuation syndrome (ADS). ADS is a common problem in patients following the interruption, dose reduction, or discontinuation of antidepressant drugs. Clinically, ADS resembles a classical drug withdrawal syndrome, albeit differing from it because antidepressants generally do not induce addiction. The growing clinical importance and prevalence of ADS necessitate novel experimental (animal) models of this disorder...
April 5, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29626425/salidroside-improves-brain-ischemic-injury-by-activating-pi3k-akt-pathway-and-reduces-complications-induced-by-delayed-tpa-treatment
#18
Wei Zuo, Feng Yan, Bo Zhang, Xiaomin Hu, Dan Mei
Cerebral ischemia causes blood-brain barrier (BBB) injury and thus increases the risk of complications secondary to thrombolysis, which limited its clinical application. This study aims to clarify the role and mechanism of salidroside (SALD) in alleviating brain ischemic injury and whether pretreatment of it could improve prognosis of delayed treatment of tissue plasminogen activator (t-PA). Rats were subjected to 3h of middle cerebral artery occlusion (MCAO) and were intraperitoneally administered with 10, 20 or 40mg/kg SALD before ischemia...
April 4, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29625084/vitamin-c-deficiency-aggravates-tumor-necrosis-factor-%C3%AE-induced-insulin-resistance
#19
Zhou Qing, Wu Xiao-Hui, Wu Xi-Mei, Zou Chao-Chun
Chronic low-grade inflammation plays a major role in the development of insulin resistance. The potential role and underlying mechanism of vitamin C, an antioxidant and anti-inflammatory agent, was investigated in tumor necrosis factor-α (TNF-α)-induced insulin resistance. Gulonolactone oxidase knockout (Gulo-/- ) mice genetically unable to synthesize vitamin C were used to induce insulin resistance by continuously pumping small doses of TNF-α for seven days, and human liver hepatocellular carcinoma cells (HepG2 cells) were used to induce insulin resistance by treatment with TNF-α...
April 3, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29608899/knockdown-of-nlrc5-inhibits-renal-fibroblast-activation-via-modulating-tgf-%C3%AE-1-smad-signaling-pathway
#20
Shiying Wang, Xinxin Zhao, Suxia Yang, Baoping Chen, Jun Shi
NLRC5, the largest member of the Nucleotide-binding domain and leucine-rich repeat (NLR) protein family, is recently proven to be a critical modulator in fibrogenesis. However, the role of NLRC5 in renal fibrosis remains unknown. In the present study, we investigated the effects of NLRC5 on transforming growth factor β1 (TGF-β1)-stimulated rat renal fibroblasts in vitro. Our results showed that the expression of NLRC5 was also obviously upregulated in renal fibrosis tissues and TGF-β1-treated NRK-49F cells...
March 30, 2018: European Journal of Pharmacology
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