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Clinical and Experimental Pharmacology & Physiology

Yong Beom Kim, Hong-Seuk Yang, Ha Jung Kim, Hey-Ran Choi, Junyong In, Soon-Young Yoon, Young Jin Ro
This in-vivo study tested the hypothesis that the modulation of acetylcholine (ACh) release by the M1 muscarinic receptor (mAChR) in the neuromuscular junction of disused muscles may affect the tensions of the muscles during the neuromuscular monitoring of a rocuronium-induced neuromuscular block and compared the results with those obtained from normal muscles. A total of 20 C57BL/6 (wild-type) and 10 α7 knock out (α7KO) mice were used in this experiment. As a pre-experimental procedure, knee and ankle joints of right hind limbs were fixed by needle pinning at the 90° flexed position...
July 13, 2018: Clinical and Experimental Pharmacology & Physiology
Tingting Zhou, Mengfan Du, Tong Zhao, Lingling Quan, Zhiyuan Zhu, Jing Chen
The Kv2.1 channel plays an important role in the regulation against pancreatic β-cell dysfunctions. Therefore, it is regarded as a promising target for drug discovery against type 2 diabetes. In the present study, we found that the small molecule 4-ethoxy-N-{[6-(2-thienyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl]methyl}aniline (ETA), a novel Kv2.1 inhibitor, may be capable of promoting glucose-stimulated insulin secretion and protecting from apoptosis in pancreatic INS-832/13 cells. The assay of ETA on type 2 diabetic mice induced by high-fat diet (HFD)/streptozocin (STZ) confirmed its potency in ameliorating glucose homeostasis...
July 13, 2018: Clinical and Experimental Pharmacology & Physiology
Katie Allen, Katie M Chuter, Katherine Fithon, Lisa Marshall, David Hauton
Orthostatic stress triggers a response to maintain cerebral perfusion and prevent syncope. Given the hypotensive effects of inorganic nitrate this response to orthostasis may be altered by acute supplementation with inorganic nitrate and modified by ethnic origin. Caucasian and SE Asian (n=30 for both), were recruited and subjected to an 'active stand test' and brachial artery blood pressure, digit blood flow and ECG were recorded. Following inorganic nitrate supplementation (10mg/kg body mass) the tests were repeated...
July 13, 2018: Clinical and Experimental Pharmacology & Physiology
Kristen R Yeung, Neroli Sunderland, Joanne M Lind, Scott Heffernan, Suzanne Pears, Bei Xu, Annemarie Hennessy, Angela Makris
Preeclampsia is a hypertensive disorder of pregnancy known to increase the risk of cardiovascular disease in mothers and offspring. Offspring exposed to a suboptimal intrauterine environment may experience altered fetal programming and subsequent long-term cardiovascular changes. This study investigated changes in the vascular response in offspring from experimental preeclampsia (EPE) induced by uterine artery ligation, in the absence of fetal growth restriction, compared to normal baboon pregnancies (controls), following a high salt diet challenge...
July 10, 2018: Clinical and Experimental Pharmacology & Physiology
Iliona Malaspinas, Ferenc Petak, Aurélie Baudat, Camille Doras, Philippe A Eigenmann, Walid Habre
Although acute prophylactic administration of atropine modulates airway responsiveness, the role of the parasympathetic nervous system in the pathogenesis of sensitization and in antigen-induced bronchoconstriction remains unclear. The aim of the present study was to determine whether blocking muscarinic receptors during chronic allergen exposure modulates lung responsiveness to the specific allergen. Forty rats were randomly assigned to one of the following five treatment groups: sensitization with saline vehicle, intraperitoneal injection of ovalbumin (1 mg) with or without atropine treatment (10 mg/kg/day), and repeated ovalbumin aerosol (1...
July 10, 2018: Clinical and Experimental Pharmacology & Physiology
Ming-Guang Zhao, Guo-Biao Liang, Hai-Feng Zhang, Guo-Feng Zhao, Yun-He Luo
Patients with intracranial aneurysm (IA) present a dysregulated immune system with lower frequency of regulatory T (Treg) cells. Here, we examined whether galectin 9 (Gal-9), the natural ligand of Tim-3, could promote Treg cells in IA patients. We first discovered that the intracellular and extracellular Gal-9 was primarily expressed by CD4+ CD25- T conventional (Tconv) cells, and also by monocytes at lower levels, but rarely by CD4+ CD25+ Treg cells. In IA patients, the Gal-9 expression was significantly lower than in healthy controls...
July 6, 2018: Clinical and Experimental Pharmacology & Physiology
Gerrit Frommeyer, Julian Wolfes, Christian Ellermann, Simon Kochhäuser, Dirk G Dechering, Lars Eckardt
The natural polyphenol resveratrol and its analogue piceatannol have various beneficial effects including antiarrhythmic properties. The aim of the present study was to examine potential electrophysiologic effects in an experimental whole-heart model of atrial fibrillation (AF). Simultaneous infusion of resveratrol (50μM) or piceatannol (10μM) in rabbit hearts resulted in an increase of atrial refractory period. Both agents induced a significant slowing of atrial conduction and of intrinsic heart rate. In both groups, a trend towards a reduction of AF and a regularization of AF was observed...
June 29, 2018: Clinical and Experimental Pharmacology & Physiology
Guang-Jun Jiao, Shi-Jun Zhang, Yi Li, Wen-Liang Wu, Hai-Chun Liu
Osteosarcoma is the most common non-hematological primary bony malignancies in children and young adults with tumor metastasis being a common event at diagnosis. Understanding the pathogenesis of metastatic osteosarcoma may help identify potential therapeutic targets. In this study, we found that the level of miR-645 in osteosarcoma tumor tissues was significantly increased compared with their paired non-tumorous tissues, and was associated with histologic grade, TNM staging, lymph metastasis and distant metastasis...
June 29, 2018: Clinical and Experimental Pharmacology & Physiology
Soad L Kabil
Liver fibrosis is a health challenge requiring alternative therapeutic approaches. Cilostazol is a selective phosphodiesterase-3 inhibitor, possesses antioxidant, anti-inflammatory and antifibrotic properties. Sirtuin1 (SIRT1) is a member of the silent information regulator 2 family. Cilostazol upregulates SIRT1 expression. Cilostazol protects against the cholestatic liver insults caused by bile duct obstruction. Involvement of SIRT1 pathway in this protective effect has not been studied yet. So, we hypothesized that SIRT1 signaling may have a role in cilostazol protective effects against bile duct ligation induced liver damages...
June 26, 2018: Clinical and Experimental Pharmacology & Physiology
Vandana R Thakur, Jayesh V Beladiya, Kiranj K Chaudagar, Anita A Mehta
TLR4 is a key component of innate immune system and activation of TLR4 signaling has the significant role in the pathogenesis of asthma. Therefore, our objective was to identify the natural TLR4 antagonist and evaluate its activity in experimentally induced asthma. Soya lecithin origin phosphatidylcholine (Soya PC) was identified as a natural TLR4 antagonist by the computational study. Based on the computational study TLR4 antagonist activity of soya PC was confirmed in in-vitro LPS induced neutrophil adhesion assay...
June 23, 2018: Clinical and Experimental Pharmacology & Physiology
Yan Wang, Wenjing An, Fei Zhang, Mengzhen Niu, Yu Liu, Ruizan Shi
The aim was to evaluate the effects and mechanisms of nebivolol on renal damage in Zucker diabetic fatty (ZDF) rats, in comparison with those of atenolol and captopril. Animals were divided into: control lean Zucker rats, ZDF rats, ZDF rats orally treated with nebivolol (10 mg/kg), atenolol (100 mg/kg) or captopril (40 mg/kg) for 6 months. Systolic blood pressure (SBP), blood glucose, kidney structure and function, plasma and kidney levels of nitric oxide (NO) and asymmetric dimethylarginine (ADMA), and oxidant status were evaluated...
June 23, 2018: Clinical and Experimental Pharmacology & Physiology
S Lee, R Rose'Meyer, C McDermott, R Chess-Williams, D J Sellers
Up to 80% of patients with diabetes mellitus develop lower urinary tract complications, most commonly diabetic bladder dysfunction (DBD). The aim of this study was to investigate the impact of diabetes on the function of the inner bladder lining (urothelium). Bladder compliance and intraluminal release of urothelial mediators (ATP and ACh) in response to distension was investigated in whole bladders isolated from 2 and 12-week streptozotocin (STZ)-diabetic rats. Intact and urothelium-denuded bladder strips were used to assess the influence of the urothelium on bladder contractility...
June 23, 2018: Clinical and Experimental Pharmacology & Physiology
Jose Sergio Possomato-Vieira, Jessica Sabbatine Chimini, Maria Luiza Santos da Silva, Carlos A Dias-Junior
Dysregulation of hydrogen sulphide (H2 S) producing enzymes has been related to hypertensive pregnancy and H2 S donor, sodium hydrosulphide (NaHS) exerts antihypertensive effects, modulates angiogenic factors production and acts as an antioxidant. Moreover, reduction in nitric oxide (NO) bioavailability is related to hypertensive pregnancy and H2 S may interact with NO, modulating its production. We aimed to investigate the NaHS effects in hypertension-in-pregnancy and also in feto-placental parameters. Female Wistar rats (200-250 g) were mated and desoxycorticosterone acetate injections followed by replacement of water by 0...
June 21, 2018: Clinical and Experimental Pharmacology & Physiology
Baoguo He, Zhiqiang Qu, Zibin Tian, Kun Zhao, Liangzhou Wei, Li Ma
Although 7,8-dihydroxyflavone (7,8-DHF), a synthetic agonist specific for TrkB, has been reported to promote intestinal dynamics, the molecular mechanisms behind its effects are not well known. In this study, we explored how 7,8-DHF affected the carbachol (CCh)-induced contraction of rat gastric muscle by way of measuring the contractile tension of muscular strips. We found that although 7,8-DHF did not directly cause contraction of gastric muscle, it enhanced the CCh-induced contractions, but not substance P- or high K+ -induced contractions...
June 21, 2018: Clinical and Experimental Pharmacology & Physiology
Rodolfo Sumayao, Philip Newsholme, Tara McMorrow
Nitric oxide (NO) has been shown to play an important role in renal physiology and pathophysiology partly through its influence on various transport systems in the kidney proximal tubule. The role of NO in the kidney dysfunction associated with the lysosomal storage disorder, cystinosis, is largely unknown. In the present study, the effects of iNOS-specific inhibitor, 1400W, on Na+ ,K+ -ATPase activity and expression, mitochondrial integrity and function, nutrient metabolism, and apoptosis were investigated in Ctns null proximal tubular epithelial cells (PTECs)...
June 20, 2018: Clinical and Experimental Pharmacology & Physiology
Toshiaki Ishizuka, Ayako Ozawa, Mieko Katsuura, Sayaka Nomura, Yasushi Satoh
Muscarinic acetylcholine receptors (mAchRs), which are expressed in various embryonic cells, may regulate neuronal differentiation. In the present study, we examined the effects of mAchR stimulation on the differentiation of mouse induced pluripotent stem (iPS) cells into neural progenitor cells (NPCs). Mouse iPS cells were cultured on ultra-low attachment dishes to induce embryoid body (EB) formation. All-trans retinoic acid (ATRA, 3 µM) and/ or pilocarpine (10 or 100 µM), a mAchR agonist, were added to EB cultures for 4 days, following which the EBs were cultured on gelatin-coated plates for 7 days...
June 19, 2018: Clinical and Experimental Pharmacology & Physiology
Jing Ling, Zhenni Ma, Ling Liu, Jie Yin, Jian Su, Fei Shen, Liqian Xie, Shaoyan Hu
Functional deficiency of ADAMTS13 causally assists in the pathology of thrombotic thrombocytopenic purpura (TTP). Previous study showed that WXXW motif is very important to the enzymatic activity of ADAMTS13. However, the functional role for a single amino acid residue within WXXW motif is still undetermined. Here, Trp390 residue within WXXW motif was substituted with Ala to generate Trp390Ala (W390A) mutant ADAMTS13. We found that W390A mutant ADAMTS13 had impaired binding affinity to its substrate Von Willebrand Factor (VWF)...
June 19, 2018: Clinical and Experimental Pharmacology & Physiology
Joanna E Kontaraki, Maria E Marketou, George E Kochiadakis, Spyros Maragkoudakis, John Konstantinou, Panos E Vardas, Fragiskos I Parthenakis
Long non-coding RNAs (lncRNAs) participate in the modulation of cardiac hypertrophy and they represent potential therapeutic targets in cardiovascular disease. We investigated the expression profiles of selected lncRNAs in peripheral blood mononuclear cells of patients with essential hypertension in relation to left ventricular hypertrophy. We assessed the expression levels of the lncRNAs MHRT, FENDRR and CARMEN using real-time reverse transcription polymerase chain reaction. Hypertensive patients showed significantly higher MHRT, FENDRR and CARMEN expression levels compared with healthy controls...
June 19, 2018: Clinical and Experimental Pharmacology & Physiology
Barbara Lisowska-Myjak, Ewa Skarżyńska, Maria Płazińska, Artur Jakimiuk
Meconium concentrations of naturally accumulated ceruloplasmin (CER), lactoferrin (LF), and neutrophil gelatinase-associated lipocalin (NGAL) and their relationships considered as a panel of acute phase proteins could be used for the assessment of fetal homeostasis. CER, LF and NGAL concentrations were measured using ELISA kits in meconium portions (n=80) collected from 19 healthy neonates. The coefficients of variation (CV) of the meconium LF (1.77) and NGAL (1.26) were about 2-fold higher than that of CER (0...
June 16, 2018: Clinical and Experimental Pharmacology & Physiology
Yali Zhu, Zhihong Liu, Miaomiao Du, Lisha Yi, Guifang Gong, Xiang Tang
Endometrial polyps (EPs) are outgrowths in the endometrium with unknown etiology. The fact that EPs can often recur after surgical removal suggests that EPs are not induced by random events but by continuous or recurrent processes in the patients. We previously demonstrated that the risk of EP development was positively associated with overactive Th17 responses. However, the requirements of Th17 upregulation are yet unclear. Here, we recruited twenty-six females with symptomatic EP and twenty-four females without EP, and peripheral mononuclear cells were harvested for the examination of circulating immunity...
June 16, 2018: Clinical and Experimental Pharmacology & Physiology
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