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European Journal of Pharmacology

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https://www.readbyqxmd.com/read/28442323/the-ace-2-ang1-7-mas-cascade-enhances-bone-structure-and-metabolism-following-angiotensin-ii-type-1-receptor-blockade
#1
Hatem M Abuohashish, Mohammed M Ahmed, Dina Sabry, Mahmoud M Khattab, Salim S Al-Rejaie
The renin angiotensin system (RAS) regulates numerous systemic functions and is expressed locally in skeletal tissues. Angiotensin1-7 (Ang1-7) is a beneficial member of the RAS, and the therapeutic effects of a large number of angiotensin receptors blockers (ARBs) are mediated by an Ang1-7-dependent cascade. This study examines whether the reported osteo-preservative effects of losartan are mediated through the angiotensin converting enzyme2 (ACE-2)/Ang1-7/Mas pathway in ovariectomized (OVX) rats. Sham and OVX animals received losartan (10mg/kg/d p...
April 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28442322/in-vitro-and-in-vivo-antitumor-activities-of-t-3764518-a-novel-and-orally-available-small-molecule-stearoyl-coa-desaturase-1-inhibitor
#2
Satoru Nishizawa, Hiroyuki Sumi, Yoshihiko Satoh, Yukiko Yamamoto, Satoshi Kitazawa, Kohei Honda, Hideo Araki, Kazuyo Kakoi, Keisuke Imamura, Masako Sasaki, Ikuo Miyahisa, Yoshinori Satomi, Ryuuichi Nishigaki, Megumi Hirayama, Kazunobu Aoyama, Hironobu Maezaki, Takahito Hara
Most cancer cells are characterized by elevated lipid biosynthesis. The rapid proliferation of cancer cells requires de novo synthesis of fatty acids. Stearoyl-CoA desaturase-1 (SCD1), a key enzyme for lipogenesis, is overexpressed in various types of cancer and plays an important role in cancer cell proliferation. Therefore, it has been studied as a candidate target for cancer therapy. In this study, we demonstrate the pharmacological properties of T-3764518, a novel and orally available small molecule inhibitor of SCD1...
April 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28438649/pathophysiological-roles-of-canstatin-on-myofibroblasts-after-myocardial-infarction-in-rats
#3
Akira Sugiyama, Muneyoshi Okada, Hideyuki Yamawaki
Myofibroblasts play an important role during remodeling process after myocardial infarction through proliferation, migration, production and degradation of extracellular matrix and contraction. Canstatin, a 24kDa polypeptide, is cleaved from α2 chain of type IV collagen, which is a major component of basement membrane around cardiomyocytes. We examined the effects of canstatin on myofibroblasts isolated from the areas of myocardial infarction. Myocardial infarction model was made by ligating left anterior descending artery of Wistar rats...
April 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28438648/the-superoxide-dismutase-mimetic-tempol-blunts-diabetes-induced-upregulation-of-nadph-oxidase-and-endoplasmic-reticulum-stress-in-a-rat-model-of-diabetic-nephropathy
#4
Miles J De Blasio, Anand Ramalingam, Anh H Cao, Darnel Prakoso, Ji-Ming Ye, Raelene Pickering, Anna M D Watson, Judy B de Haan, David M Kaye, Rebecca H Ritchie
Endoplasmic reticulum (ER) stress contributes to progression of diabetic nephropathy, which promotes end-stage renal failure in diabetic patients. This study was undertaken to investigate the actions of tempol and ramipril, pharmacological agents that target the consequences of NADPH oxidase, on diabetic nephropathy in a rat model of type 1 diabetes, with an emphasis on markers of ER stress. Male Sprague-Dawley rats were injected intravenously with a single bolus of streptozotocin (55mg/kg) to induce type 1 diabetes...
April 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28438647/effects-of-bms-902483-an-%C3%AE-7-nicotinic-acetylcholine-receptor-partial-agonist-on-cognition-and-sensory-gating-in-relation-to-receptor-occupancy-in-rodents
#5
Rick L Pieschl, Regina Miller, Kelli M Jones, Debra J Post-Munson, Ping Chen, Kimberly Newberry, Yulia Benitex, Thaddeus Molski, Daniel Morgan, Ivar M McDonald, John E Macor, Richard E Olson, Yukiko Asaka, Siva Digavalli, Amy Easton, James Herrington, Ryan S Westphal, Nicholas J Lodge, Robert Zaczek, Linda J Bristow, Yu-Wen Li
The α7 nicotinic acetylcholine receptor is thought to play an important role in human cognition. Here we describe the in vivo effects of BMS-902483, a selective potent α7 nicotinic acetylcholine receptor partial agonist, in relationship to α7 nicotinic acetylcholine receptor occupancy. BMS-902483 has low nanomolar affinity for rat and human α7 nicotinic acetylcholine receptors and elicits currents in cells expressing human or rat α7 nicotinic acetylcholine receptors that are about 60% of the maximal acetylcholine response...
April 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28435093/plaque-angiogenesis-and-intraplaque-hemorrhage-in-atherosclerosis
#6
Laura Parma, Fabiana Baganha, Paul H A Quax, Margreet R de Vries
Acute cardiovascular events, due to rupture or erosion of an atherosclerotic plaque, represent the major cause of morbidity and mortality in patients. Growing evidence suggests that plaque neovascularization is an important contributor to plaque growth and instability. The vessels' immaturity, with profound structural and functional abnormalities, leads to recurrent intraplaque hemorrhage. This review discusses new insights of atherosclerotic neovascularization, including the effects of leaky neovessels on intraplaque hemorrhage, both in experimental models and humans...
April 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28435094/diammonium-glycyrrhizinate-alleviates-hepatopulmonary-syndrome-via-restoring-superoxide-dismutase-3-activity-in-rats
#7
Xin Zhao, Jinyu Liu, Shijun Yang, Chen Chen, He Yin, Ting Li, Qiuting Wang, Xiaoya Li, Yulin Lin, Dayong Cai
Hepatopulmonary syndrome (HPS) has a fatal hypoxemia from pulmonary shunts. Superoxide dismutase 3 (SOD3) deficiency involves in this pathogenesis. The purpose of this study was to investigate the underlying mechanisms of diammonium glycyrrhizinate (DG) on HPS via SOD3. Carbon tetrachloride induced HPS rats were treated with captopril or DG for 56 days. Blood gas, pulmonary artery pressures, and histological changes were measured. Molecule dynamics of inducible (iNOS), endothelial (eNOS), neuronal nitric oxide synthase (nNOS) and SOD3 were assessed by immunohistochemistry, quantitative RT-PCR and western blot...
April 20, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28435092/-terpinen-4-ol-changes-intracellular-ca-2-handling-and-induces-pacing-disturbance-in-rat-hearts
#8
Antonio Nei Santana Gondim, Aline Lara, Artur Santos-Miranda, Danilo Roman-Campos, Sandra Lauton-Santos, José Evaldo Rodrigues Menezes-Filho, Carla Maria Lins de Vasconcelos, Eduardo Antonio Conde-Garcia, Silvia Guatimosim, Jader S Cruz
(-)-Terpinen-4-ol is a naturally occurring plant monoterpene and has been shown to have a plethora of biological activities. The objective of this study was to investigate the effects of (-)-terpinen-4-ol on the rat heart, a key player in the control and maintenance of arterial blood pressure. The effects of (-)-terpinen-4-ol on the rat heart were investigated using isolated left atrium isometric force measurements, in vivo electrocardiogram (ECG) recordings, patch clamp technique, and confocal microscopy. It was observed that (-)-terpinen-4-ol reduced contraction force in an isolated left atrium at millimolar concentrations...
April 20, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28433657/mir-938-promotes-colorectal-cancer-cell-proliferation-via-targeting-tumor-suppressor-phlpp2
#9
Chang-Feng Li, Yong-Chao Li, Jing-Peng Jin, Zhen-Kun Yan, Dan-Dan Li
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Although the development of therapy approaches, the outcome of CRC patients still is poor, understanding the biological mechanism of CRC progression is critical to improve the treatment strategies. miRNAs regulate CRC progression, we found miR-938 was upregulated in CRC tissues and cells, MTT assay, colony formation assay and soft agar growth assay suggested miR-938 overexpression promoted CRC cell proliferation, miR-938 knockdown inhibited CRC cell proliferation...
April 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28433656/impaired-endothelium-derived-hyperpolarization-type-relaxation-in-superior-mesenteric-arteries-isolated-from-female-otsuka-long-evans-tokushima-fatty-rats
#10
Takayuki Matsumoto, Shota Kobayashi, Makoto Ando, Shun Watanabe, Maika Iguchi, Kumiko Taguchi, Tsuneo Kobayashi
Endothelium-derived hyperpolarization (EDH) is an important signaling mechanism of endothelium-dependent vasorelaxation, and little attention has been paid to the EDH-type responses in female metabolic syndrome such as that observed with type-2 diabetes. We previously reported that EDH-type relaxation was impaired in superior mesenteric arteries from male Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of type-2 diabetes, however, the response was unclear in female OLETF rat. Thus, the aim of this study was to examine if EDH-type relaxation was altered in superior mesenteric arteries isolated from female OLETF rats compared to age-matched, control female Long-Evans Tokushima Otsuka (LETO) rats at age 50-59 weeks...
April 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28428008/force-development-and-intracellular-ca-2-in-intact-cardiac-muscles-from-gravin-mutant-mice
#11
Zhitao Li, Sonal Singh, Santosh V Suryavanshi, Wengang Ding, Xiaoxu Shen, Cori S Wijaya, Wei Dong Gao, Bradley K McConnell
Gravin (AKAP12) is an A-kinase-anchoring-protein that scaffolds protein kinase A (PKA), β2-adrenergic receptor (β2-AR), protein phosphatase 2B and protein kinase C. Gravin facilitates β2-AR-dependent signal transduction through PKA to modulate cardiac excitation-contraction coupling and its removal positively affects cardiac contraction. Trabeculae from the right ventricles of gravin mutant (gravin-t/t) mice were employed for force determination. Simultaneously, corresponding intracellular Ca(2+) transient ([Ca(2+)]i) were measured...
April 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28419822/inhibitory-effects-of-losartan-and-azelnidipine-on-augmentation-of-blood-pressure-variability-induced-by-angiotensin-ii-in-rats
#12
Danfeng Jiang, Yukiko Kawagoe, Kenji Kuwasako, Kazuo Kitamura, Johji Kato
Increased blood pressure variability has been shown to be associated with cardiovascular morbidity and mortality. Recently we reported that continuous infusion of angiotensin II not only elevated blood pressure level, but also increased blood pressure variability in a manner assumed to be independent of blood pressure elevation in rats. In the present study, the effects of the angiotensin type I receptor blocker losartan and the calcium channel blocker azelnidipine on angiotensin II-induced blood pressure variability were examined and compared with that of the vasodilator hydralazine in rats...
April 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28416373/inhibition-effects-of-chlorogenic-acid-on-benign-prostatic-hyperplasia-in-mice
#13
Ya Huang, Huaguo Chen, Xin Zhou, Xingdong Wu, Enming Hu, Zhengmeng Jiang
This study aimed to evaluate the inhibitory effects and explore mechanisms of chlorogenic acid against testosterone-induced benign prostatic hyperplasia (BPH) in mice. Benign prostatic hyperplasia model was induced in experimental groups by daily subcutaneous injections of testosterone propionate (7.5mg/kg/d) consecutively for 14 d. A total of 60 mice were randomly divided into six groups: (Group 1) normal control group, (Group 2) benign prostatic hyperplasia model control group, (Group 3) benign prostatic hyperplasia mice treated with finasteride at a dose of 1mg/kg, (Group 4) benign prostatic hyperplasia mice treated with chlorogenic acid at dose levels of 0...
April 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28416372/effects-of-bilobalide-ginkgolide-b-and-picrotoxinin-on-gabaa-receptor-modulation-by-structurally-diverse-positive-modulators
#14
Chiu Chin Ng, Rujee K Duke, Tina Hinton, Graham A R Johnston
Anxiolytics and anticonvulsants generally positively modulate the action of GABA, whereas many convulsants (including the chloride channel blocker picrotoxinin) negatively modulate the action of GABA on GABAA receptors. Like picrotoxinin, bilobalide and ginkgolide B, active constituents of Ginkgo biloba, have been shown to negatively modulate the action of GABA at α1β2γ2L GABAA receptors. However, unlike picrotoxinin, bilobalide and ginkgolide B are not known to cause convulsions. We have assessed the action of bilobalide, ginkgolide B and picrotoxinin on a range of GABAA modulators (etomidate, loreclezole, propofol, thiopentone sodium, diazepam, and allopregnanolone), using two-electrode voltage clamp electrophysiology at recombinant α1β2γ2L GABAA receptors expressed in Xenopus oocytes...
April 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28416371/modulation-by-nadph-oxidase-of-the-chronic-cardiovascular-and-autonomic-interaction-between-cyclosporine-and-nsaids-in-female-rats
#15
Ahmed F El-Yazbi, Karim S Ibrahim, Hanan M El-Gowelli, Nevine M El-Deeb, Mahmoud M El-Mas
Cyclosporine (CSA) and nonsteroidal antiinflammatory drugs (NSAIDs) are used together to manage arthritic disorders with an immune component. Previous reports showed contrasting effects for NSAIDs on CSA nephrotoxicity and acute elevations in blood pressure. Both effects were ameliorated or exaggerated after selective cyclooxygenase-2 (COX2) and nonselective COX inhibition, respectively. Here we investigated: (i) the interaction of CSA with NSAIDs possessing variable COX1/COX2 selectivities on hemodynamic, left ventricular (LV) and cardiac autonomic and histologic profiles, and (ii) role of NADPH-oxidase (NOX)/Rho-kinase (ROCK) pathway in the interaction...
April 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28414056/protective-effects-of-glycyrrhizic-acid-against-non-alcoholic-fatty-liver-disease-in-mice
#16
Xue Sun, Xingping Duan, Changyuan Wang, Zhihao Liu, Pengyuan Sun, Xiaokui Huo, Xiaodong Ma, Huijun Sun, Kexin Liu, Qiang Meng
Non-alcoholic fatty liver disease (NAFLD) has become a predictive factor of death from many diseases. The purpose of the present study is to investigate the protective effect of glycyrrhizic acid (GA), a natural triterpene glycoside, on NAFLD induced by a high-fat diet (HFD) in mice, and further to elucidate the mechanisms underlying GA protection. GA treatment significantly reduced the relative liver weight, serum ALT, AST activities, levels of serum lipid, blood glucose and insulin. GA suppressed lipid accumulation in liver...
April 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28414057/non-invasive-assessment-of-liver-fibrosis-in-patients-with-hbv-related-chronic-liver-disease-undergoing-antiviral-treatment-a-preliminary-study
#17
Cristina Stasi, Elena Salomoni, Umberto Arena, Giampaolo Corti, Paolo Montalto, Filippo Bartalesi, Fabio Marra, Giacomo Laffi, Stefano Milani, Anna Linda Zignego, Massimo Pinzani
In chronic hepatitis B (CHB) patients, fibrosis assessment during antiviral treatment is a key step in the clinical management. Aim of this study was to evaluate the performance of elastography in assessing fibrosis stage in CHB before and after two years of nucleoside/nucleotide analogues (NUC) treatment in comparison with indirect serum markers. CHB diagnosis was made according to standard criteria. A clinical and virological evaluation was performed at baseline and again at 3, 6, 9, 12 18, and 24 months during treatment...
April 13, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28414055/dihydromyricetin-attenuated-ang-ii-induced-cardiac-fibroblasts-proliferation-related-to-inhibitory-of-oxidative-stress
#18
Qiuyi Song, Lulu Liu, Jin Yu, Jingyao Zhang, Mengting Xu, Linlin Sun, Huiqin Luo, Zhaosong Feng, Guoliang Meng
Dihydromyricetin (DMY) is one of the most important flavonoids in vine tea, which showed several pharmacological effects. However, information about the potential role of DMY on angiotensin II (Ang II) induced cardiac fibroblasts proliferation remains unknown. In the present study, cardiac fibroblasts isolated from neonatal Sprague-Dawley rats were pretreated with different concentrations of DMY (0- 320μM) for 4h, or DMY (80μM) for different time (0-24h), followed by Ang II (100nM) stimulation for 24h, Then number of cardiac fibroblasts and content of hydroxyproline was measured...
April 13, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28414054/endothelium-dependent-vasorelaxant-effect-of-procyanidin-b2-on-human-internal-mammary-artery
#19
Aleksandra Novakovic, Marija Marinko, Goran Jankovic, Ivan Stojanovic, Predrag Milojevic, Dragoslav Nenezic, Vladimir Kanjuh, Qin Yang, Guo-Wei He
The aim of the present study was to investigate and characterize vasorelaxant effect of procyanidin B2 on human internal mammary artery (HIMA) as one of the mechanisms of its protective effect against vascular risk. Procyanidin B2 induced strong concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Pretreatment with L-NAME, a NO synthase inhibitor, hydroxocobalamin, a NO scavenger, and ODQ, an inhibitor of soluble guanylate cyclase, significantly inhibited procyanidin B2-induced relaxation of HIMA, while indomethacin, a cyclooxygenase inhibitor, considerably reduced effects of low concentrations...
April 13, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28412373/mechanistic-evaluation-of-tapentadol-in-reducing-the-pain-perception-using-in-vivo-brain-and-spinal-cord-microdialysis-in-rats
#20
Vijay Benade, Ramakrishna Nirogi, Gopinadh Bhyrapuneni, Saivishal Daripelli, Ganesh Ayyanki, Shantaveer Irappanavar, Ranjithkumar Ponnamaneni, Arunkumar Manoharan
Role of monoamine neurotransmitters in the modulation of emotional and pain processing in spinal cord and brain regions is not well known. Tapentadol, a norepinephrine reuptake inhibitor with µ-opioid receptor agonistic activity has recently been introduced for the treatment of moderate to severe pain. The objective of the present study was to examine the effects of tapentadol on modulation of monoamines in the prefrontal cortex and dorsal horn using brain microdialysis. Tapentadol was administered intraperitoneally at 4...
April 12, 2017: European Journal of Pharmacology
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