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Clinical and Experimental Pharmacology & Physiology

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https://www.readbyqxmd.com/read/28440910/subacute-pyridostigmine-exposure-increases-heart-rate-recovery-and-cardiac-parasympathetic-tone-in-rats
#1
Manushree Bharadwaj, Carey Pope, Michael Davis, Stuart Katz, Christian Cook, Lara Maxwell
Heart rate recovery (HRR) describes the rapid deceleration of heart rate after strenuous exercise and is an indicator of parasympathetic tone. A reduction in parasympathetic tone occurs in patients with congestive heart failure, resulting in prolonged HRR. Acetylcholinesterase inhibitors, such as pyridostigmine, can enhance parasympathetic tone by increasing cholinergic input to the heart. The objective of this study was to develop a rodent model of HRR to test the hypothesis that subacute pyridostigmine administration decreases cholinesterase activity and accelerates HRR in rats...
April 25, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28440887/microrna-regulation-of-extracellular-matrix-components-in-the-process-of-atherosclerotic-plaque-destabilization
#2
REVIEW
Michal Kowara, Agnieszka Cudnoch-Jedrzejewska, Grzegorz Opolski, Pawel Wlodarski
The process of atherosclerotic plaque destabilization, leading to myocardial infarction, is still not fully understood. The pathway - composed of structural and regulatory proteins of the extracellular matrix (ECM) such as collagen, elastin, small leucine-rich proteoglycans, metalloproteinases, cathepsins and serine proteases - is one potential way of atherosclerotic plaque destabilization. The expression of these proteins is controlled by different microRNA molecules. The goal of this paper is to summarize the current investigations and knowledge about ECM in the process of atherosclerotic plaque destabilization, giving special attention to epigenetic expression regulation by microRNA...
April 25, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28432808/mechanism-of-the-vasorelaxant-effect-induced-by-trans-4-methyl-%C3%AE-nitrostyrene-a-synthetic-nitroderivative-in-rat-thoracic-aorta
#3
Taylena Maria Teófilo, Loeste Arruda-Barbosa, Jussara Mathyelle Rodrigues-Silva, Joyce Karen Lima Vale, Rosivaldo Dos Santos Borges, Gloria Pinto Duarte, Pedro Jorge Caldas Magalhães, Saad Lahlou
Mechanisms underlying the vasorelaxant effects of trans-4-methyl-β-nitrostyrene (T4MeN) were studied in rat aortic rings. In endothelium-intact preparations, T4MeN fully and similarly relaxed contractions induced by phenylephrine (PHE) (IC50 = 61.41 [35.40-87.42] μM) and KCl (IC50 = 83.50 [56.63-110.50] μM). The vasorelaxant effect of T4MeN was unchanged by endothelium removal, pretreatment with L-NAME, indomethacin, tetraethylammonium, ODQ or MDL-12,330A. Under Ca(2+) -free conditions, T4MeN significantly reduced with a similar potency: (i) phasic contractions induced by PHE, but not by caffeine; (ii) contractions due to CaCl2 in aortic preparations stimulated with PHE (in the presence of verapamil) or high KCl; (iii) contractions evoked by the restoration of external Ca(2+) levels after depletion of intracellular Ca(2+) stores in the presence of thapsigargin...
April 22, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28429868/clarification-of-serotonin-induced-effects-in-peripheral-artery-disease-observed-through-the-femoral-artery-response-in-models-of-diabetes-and-vascular-occlusion-the-role-of-calcium-ions
#4
Marko Stojanović, Milica Prostran, Radmila Janković, Miroslav Radenković
Recent findings have demonstrated that serotonin is an important participant in the development and progression of peripheral artery diseases. Taking this into consideration, the goals of this study were to investigate the effects of serotonin on isolated Wistar rat femoral arteries in both healthy and diabetic animals, with and without artery occlusion, with a particular focus on determining the role of calcium in this process. Contraction experiments with serotonin on intact and denuded femoral artery rings, in the presence or absence of nifedipine and ouabain (both separately, or in combination), as well as Ca(2+) -free Krebs-Ringer bicarbonate solution were performed...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28429857/ndufa4l2-protects-against-ischemia-reperfusion-induced-cardiomyocyte-apoptosis-and-mitochondrial-dysfunction-by-inhibiting-complex-i
#5
Jianhua Li, Caiyan Bai, Junxia Guo, Wanqian Liang, Jingning Long
Myocardial ischemia/reperfusion (I/R) injury may cause the apoptosis of cardiomyocytes as well as mitochondrial dysfunction. The aims of the present study were to investigate whether NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) on myocardial ischemia-reperfusion (I/R) injury and the underlying molecular mechanism. The hypoxia-reperfusion (H/R) model was established in vitro using H9c2 cells to simulate I/R injury. NDUFA4L2 and complex I expression levels were detected using RT-PCR and western blot...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28429852/anti-inflammatory-and-retinal-protective-effects-of-capsaicin-on-ischemia-induced-injuries-through-the-release-of-endogenous-somatostatin
#6
Jun Wang, Wenke Tian, Shuaiwei Wang, Wenqiang Wei, Dongdong Wu, Honggang Wang, Li Wang, Ruisheng Yang, Ailing Ji, Yanzhang Li
The mechanisms regarding the retinal protective and anti-inflammatory effects of capsaicin (CAP) remain unclear. Somatostatin is contained in CAP-sensitive sensory neurons, including nerve terminals, from which it can be released by capsaicin. The present study provides a novel neurohumoral regulatory mechanism for CAP-induced-endogenous somatostatin in a retinal ischemic-reperfusion (I/R) mouse model. CAP (0.5 mg kg(-1) ) was injected subcutaneously 5 min after I/R. A selective somatostatin-depleting agent, cysteamine, was applied subcutaneously 4 hours before the experiment to examine the effects of endogenous somatostatin...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28429540/silencing-of-astrocyte-elevated-gene-1-inhibits-proliferation-and-migration-and-induces-apoptosis-in-melanoma
#7
Yue Zhang, Ge Peng, Ying Wang, Lixia Cui, Wenqing Wu, Luan Wang, Chengyu Liu, Xiuping Han
Melanoma is an aggressive skin malignancy with a high mortality. Astrocyte elevated gene-1 (AEG-1), a downstream target of ras and c-myc, has been implicated in the development of multiple tumors, yet its role in melanoma remains unclear. In the present study, the role of AEG-1 in melanoma was explored through AEG-1 silencing. Our results showed that silencing of AEG-1 inhibited proliferation of melanoma cells and induced cell cycle arrest, accompanied by reduced levels of cyclinA, cyclinB, cyclinD1, cyclinE and cyclin dependent kinase 2...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28429502/involvement-of-erk1-2-in-cx43-depression-induced-by-macrophage-migration-inhibitory-factor-in-atrial-myocytes
#8
Xin Li, Fang Rao, Chun-Yu Deng, Wei Wei, Fang-Zhou Liu, Hui Yang, Zhao-Yu Wang, Su-Juan Kuang, Xiao-Yan Chen, Yu-Mei Xue, Shu-Lin Wu
Connexin 43 (Cx43) plays an important role in the pathogenesis of atrial fibrillation (AF). The present study sought to investigate the effect of macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, on Cx43 expression and activity and determine the intracellular signaling pathways. Cx43 protein and mRNA levels were assayed using immunofluorescence, real-time PCR, and western blot. We found that increased MIF and extracellular regulated protein kinases (ERK) expression was accompanied by a significant reduction in Cx43 protein expression in atrial tissues from patients with AF compared with those with sinus rhythm...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28425217/the-release-of-pro-inflammatory-cytokines-is-mediated-via-map-kinases-rather-than-inflammasome-signaling-pathway-in-keratinocytes
#9
Thomas Ondet, Béatrice Muscatelli-Groux, Cédric Coulouarn, Sacha Robert, Thomas Gicquel, Aude Bodin, Vincent Lagente, Jean-Alexis Grimaud
Toll like receptors (TLRs) are expressed in the skin and airway epithelial tissues, which are the most important sites of host-pathogen interactions. TLRs recognize the three-dimensional structure of pathogen associated molecules and are thus useful markers of the innate immune response. Here, we investigated the role of lipopolysaccharides (LPS) and monosodium urate (MSU) crystals in the activation of the TLR and Nod Like Receptors (NLR) pathways in human keratinocytes. Analysis of the inflammasome compounds revealed that NLRP3 and TLR4, both of which are components of inflammasome complexes involved in the activation of IL-1β, were not expressed in keratinocytes...
April 20, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28419527/the-rectosigmoid-brake-review-of-an-emerging-neuromodulation-target-for-colorectal-functional-disorders
#10
Anthony Y Lin, Phil G Dinning, Tony Milne, Ian P Bissett, Gregory O'Grady
The regulation of gastrointestinal motility encompasses several overlapping mechanisms including highly regulated and coordinated neurohormonal circuits. Various feedback mechanisms or 'brakes' have been proposed. While duodenal, jejunal, and ileal brakes are well described, a putative distal colonic brake is less well defined. Despite the high prevalence of colonic motility disorders, there is little knowledge of colonic motility owing to difficulties with organ access and technical difficulties in recording detailed motor patterns along its entire length...
April 16, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28409855/the-mobility-of-mitochondria-intercellular-trafficking-in-health-and-disease
#11
Michael V Berridge, Jiri Neuzil
The view that genes are constrained within somatic cells is challenged by in vitro evidence, and more recently by in vivo studies which demonstrate that mitochondria with their mitochondrial DNA (mtDNA) payload not only can, but do move between cells in tumour models and in mouse models of tissue damage. Using mouse tumour cell models without mtDNA to reflect mtDNA damage, we have shown that these cells grow tumours only after acquiring mtDNA from cells in the local microenvironment resulting in respiration recovery, tumorigenesis and metastasis...
April 13, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28394459/ergogenic-properties-of-metformin-in-simulated-high-altitude
#12
Rebecca L Scalzo, Hunter L Paris, Scott E Binns, Janelle L Davis, Joseph W Beals, Christopher L Melby, Gary J Luckasen, Matthew S Hickey, Benjamin F Miller, Karyn L Hamilton, Christopher Bell
Metformin augments glucose/glycogen regulation and may acutely promote fatigue resistance during high-intensity exercise. In hypobaric environments, such as high altitude, the important contribution of carbohydrates to physiological function is accentuated as glucose/glycogen dependence is increased. Because hypoxia/hypobaria decreases insulin sensitivity, replenishing skeletal muscle glycogen in high altitude becomes challenging and subsequent physical performance may be compromised. We hypothesized that in conditions where glycogen repletion was critical to physical outcomes, metformin would attenuate hypoxia-mediated decrements in exercise performance...
April 10, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28394450/effects-of-presynaptic-muscarinic-receptor-blockade-on-neuromuscular-transmission-as-assessed-by-the-train-of-four-and-the-tetanic-fade-response-to-rocuronium
#13
Yong Beom Kim, Sangseok Lee, Kyeong Cheon Lee, Ha Jung Kim, Young Jin Ro, Hong-Seuk Yang
This study investigated the effect of muscarinic M1 and M2 receptor antagonists on the rocuronium-induced train of four (TOF) fade and tetanic fade, respectively. Ex-vivo phrenic nerves/diaphragms were obtained from adult Sprague-Dawley rats and, stabilized in Krebs buffer, and the nerve-stimulated muscle TOF fade was observed at 20 s intervals. For the TOF study, phrenic nerve/diaphragms were incubated with pirenzepine (an M1 blocker) at concentrations of 0 nM (control), 10 nM (PZP10), or 100 nM (PZP100). Rocuronium was then administered incrementally until the first twitch tension (T1) had depressed by >95% during TOF stimulation...
April 10, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28394420/tiron-ameliorates-high-glucose-induced-cardiac-myocyte-apoptosis-by-pkc%C3%AE-dependent-inhibition-of-osteopontin
#14
Ping Jiang, Deling Zhang, Hong Qiu, Xianqi Yi, Yemin Zhang, Yingkang Cao, Bo Zhao, Zhongyuan Xia, Changhua Wang
Tiron functions as an effective antioxidant alleviating the intracellular reactive oxygen species (ROS) or the acute toxic metal overload. The previous studies have shown that cardiac myocyte apoptosis can be effectively inhibited by tiron administration in streptozotocin (STZ)-induced diabetic rats, primary neonatal rat cardiomyocytes (NRVMs), and H9c2 embryonic rat cardiomyocytes. However, the underlying signaling mechanism is ill-defined. In the present study, we found that tiron supplementation significantly inhibited apoptosis of high glucose (HG)-treated NRVMs and the left ventricular cardiomyocytes from STZ-diabetic rat, accompanied with a reduction of osteopontin (OPN) levels as well as an inhibition of PKCδ phosphorylation...
April 10, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28378496/c-reactive-protein-and-ageing
#15
Ying Tang, Erik Fung, Anping Xu, Hui-Yao Lan
Increasing evidence shows that C-reactive protein (CRP) is not only an inflammatory biomarker but also an important risk factor associated with ageing-related diseases including cardiovascular disease, hypertension, diabetes mellitus, and kidney disease. Recent studies have demonstrated that CRP is pathogenic in a number of diseases including hypertensive cardiovascular and kidney complications, diabetic nephropathy, and acute and chronic kidney diseases. It is well known that CRP binds its receptor, CD32/CD64, to induce the process of inflammation by activating the NF-κB signalling pathway...
April 4, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28378467/compared-effects-on-cerebral-oxygenation-of-ephedrine-vs-phenylephrine-to-treat-hypotension-during-carotid-endarterectomy
#16
Jugurtha Aliane, Christian Dualé, Nader Guesmi, Charlotte Baud, Eugenio Rosset, Bruno Pereira, Damien Bouvier, Pierre Schoeffler
While both ephedrine and phenylephrine are currently used to treat hypotension occurring during carotid endarterectomy (CEA) under general anaesthesia, phenylephrine may have deleterious effects on the cerebral watershed, due to its exclusively vasoconstrictive action. In this controlled, double-blind randomised trial, we compared the effects of ephedrine and phenylephrine administered in a standardised algorithm to treat the first hypotensive event occurring since induction of anaesthesia until carotid cross-clamping...
April 4, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28370165/neuroprotective-effects-of-a-novel-poly-adp-ribose-polymerase-1-inhibitor-jpi-289-in-hypoxic-rat-cortical-neurons
#17
Youngchul Kim, Young Seo Kim, Min-Young Noh, Hanchang Lee, Boyoung Joe, Hyun Young Kim, Jeongmin Kim, Seung Hyun Kim, Jiseon Park
Excessive activation of Poly (ADP-ribose) polymerase-1 (PARP-1) is known to develop neuronal apoptosis, necrosis and inflammation after ischemic brain injury. Therefore, PARP-1 inhibition after ischemic stroke has been attemptedin successful animal studies. The purpose of present work was to develop a novel water soluble PARP-1 inhibitor (JPI-289) and explore its neuroprotective effect on ischemic injury in an in vitro model. The half-life of JPI-289 after Intravenous or oral administration in rats was relatively long (1...
April 2, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28345252/amplification-of-fsh-signaling-by-cftr-and-nuclear-soluble-adenylyl-cyclase-in-the-ovary
#18
Hui Chen, Hsiao Chang Chan
cAMP/PKA pathway is one of the most important signaling pathways widely distributed in most eukaryotic cells. The activation of the canonical cAMP/PKA pathway depends on transmembrane adenylyl cyclase (tmAC). Recently, soluble adenylyl cyclase (sAC), which is activated by HCO3(-) or Ca(2+) , emerges to provide an alternative way to activate cAMP/PKA pathway with the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl(-) / HCO3(-) -conducting anion channel, as a key player. This review summarizes new progress in the investigation of the CFTR/HCO3(-) -dependent sAC signaling and its essential role in various reproductive processes, particularly in ovarian functions...
March 27, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28345145/air-pollution-and-short-term-clinical-outcomes-of-patients-with-acute-myocardial-infarction
#19
Min Woo Lee, Byoung Geol Choi, Suhng Wook Kim, Seung-Woon Rha, Min Suk Shim, Dae Jin Kim, Hong Seog Seo, Dong Joo Oh, Myung Ho Jeong
1.Ambient air pollution is well-known to be a serious risk factor for cardiovascular diseases, stroke, and death. However, the association between air pollutants (AP) exposure and short-term clinical outcomes in acute myocardial infarction (AMI) patients (pts) is not well elucidated yet. 2.In the present study, 37,880 AMI pts were enrolled finally from October 2005 to December 2013 in a nationwide large-scale, prospective, multicenter Korea AMI registry (KAMIR registry; http://www.kamir.or.kr). We obtained data on AP (e...
March 27, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28323356/on-the-use-of-one-sided-statistical-tests-in-biomedical-research
#20
Ricardo Murphy
There is a tendency to automatically use two-sided tests to assess the statistical significance of experimental results. Yet if a theory predicts the direction of an experimental outcome, or if for some practical (e.g. clinical) reason an outcome in that direction is the only one of interest, then it makes sense to use a one-sided test. The use of a two-sided test in these situations will lead to too many false negatives. Consequently treatment effects that corroborate a theory or that are of practical importance may be missed...
March 21, 2017: Clinical and Experimental Pharmacology & Physiology
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