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Clinical and Experimental Pharmacology & Physiology

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https://www.readbyqxmd.com/read/28323356/on-the-use-of-one-sided-statistical-tests-in-biomedical-research
#1
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
https://www.readbyqxmd.com/read/28316086/cardiac-fibrosis-in-the-ageing-heart-contributors-and-mechanisms
#2
Lu Lu, Jingbin Guo, Yue Hua, Kevin Huang, Ruth Magaye, Jake Cornell, Darren J Kelly, Christopher Reid, Danny Liew, Yingchun Zhou, Aihua Chen, Wei Xiao, Qiang Fu, Bing Hui Wang
Cardiac fibrosis refers to an excessive deposition of extracellular matrix (ECM) in cardiac tissue. Fibrotic tissue is stiffer and less compliant, resulting in subsequent cardiac dysfunction and heart failure. Cardiac fibrosis in the ageing heart may involve activation of fibrogenic signalling and inhibition of anti-fibrotic signalling, leading to an imbalance of ECM turnover. Excessive accumulation of ECM such as collagen in older patients contributes to progressive ventricular dysfunction. Overexpression of collagen is derived from various sources, including higher levels of fibrogenic growth factors, proliferation of fibroblasts and cellular trans-differentiation...
March 18, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28316077/development-of-resistance-to-serotonin-induced-itch-in-bile-duct-ligated-mice
#3
Sattar Ostadhadi, Nazgol-Sadat Haddadi, Arash Foroutan, Ehsan Azimi, Sarina Elmariah, Ahmad-Reza Dehpour
Cholestatic itch can be severe and significantly impair the quality of life of patients. Serotonin system is implicated in cholestatic itch; however, the pruritogenic properties of serotonin have not been evaluated in cholestatic mice. Here, we investigated the serotonin-induced itch in cholestatic mice which was induced by bile duct ligation (BDL). Serotonin, sertraline or saline were administered intradermally to the rostral back area in BDL and sham-operated (SHAM) mice, and the scratching behavior was videotaped for 1 hour...
March 18, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28316073/arrhythmic-effects-of-epac-mediated-ryanodine-receptor-activation-in-langendorff-perfused-murine-hearts-are-associated-with-reduced-conduction-velocity
#4
Mengye Li, Sandeep Hothi, Samantha C Salvage, Kamalan Jeevaratnam, Andrew A Grace, Christopher L-H Huang
Recent papers have attributed arrhythmic substrate in murine RyR2-P2328S hearts to reduced action potential (AP) conduction velocities (CV), reflecting acute functional inhibition and/or reduced expression of sodium channels. We explored for acute effects of direct Epac (exchange protein directly activated by cAMP)-mediated ryanodine receptor-2 (RyR2) activation on arrhythmic substrate and CV. Monophasic action potential recordings demonstrated that initial steady (8-Hz) extrinsic pacing elicited ventricular tachycardia (VT) in 0 of 18 Langendorff-perfused wild-type mouse ventricles before pharmacological intervention...
March 18, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28306174/the-cardiac-l-type-calcium-channel-alpha-subunit-is-a-target-for-direct-redox-modification-during-oxidative-stress-the-role-of-cysteine-residues-in-the-alpha-interacting-domain
#5
Padmapriya Muralidharan, Henrietta Cserne Szappanos, Evan Ingley, Livia C Hool
Cardiovascular disease is the leading cause of death in the Western world. The incidence of cardiovascular disease is predicted to further rise with the increase in obesity and diabetes and with the ageing population. Even though the survival rate from ischemic heart disease has improved over the past 30 years, many patients progress to a chronic pathological condition, known as cardiac hypertrophy that is associated with an increase in morbidity and mortality. Reactive oxygen species (ROS) and calcium play an essential role in mediating cardiac hypertrophy...
March 17, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28294385/potential-excitatory-role-of-nitric-oxide-on-2-deoxy-d-glucose-induced-gastric-motility-in-rats
#6
A M Sevgili, Z D Balkanci, A Erdem
Previous studies have shown that 2-deoxy-d-glucose (2-DG) increases gastric motility via the vagus nerve, but the underlying mechanism remains elusive. Since nitric oxide (NO) is involved in gastric motility, a possible interplay between 2-DG and NO can be suggested. In the present study, Wistar rats (250-350 g) of both sexes were intravenously injected with 2-DG (200 mg·kg(-1) ), and the effects of the intravenous injection of the nitric oxide synthase (NOS) inhibitors; nitro-l-arginine methyl ester (l-NAME, 10 mg·kg(-1) ) and N(ω) -nitro-l-arginine (l-NNA, 10 mg·kg(-1) ) were investigated...
March 13, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28273404/association-of-genetic-polymorphisms-of-claudin-1-with-small-vessel-vascular-dementia
#7
Vivek Srinivasan, Nady Braidy, Ying Hua Xu, Peter Xie, Kiran Kancherla, Sashiruben Chandramohan, Eunice Kar Wing Chan, Daniel Ky Chan
The most recent hypothesis of the development of small vessel vascular dementia (VaD) emphasises the role of blood-brain barrier (BBB) dysfunction. It is hypothesised that certain genetic polymorphisms of the BBB tight junction claudin-1 protein, in combination with adverse environmental risk factors, increase the risk of BBB dysfunction and small vessel VaD. In this case-control study, 97 control participants, with a mean Mini Mental State Exam (MMSE) score of 29.1, and 38 VaD participants were recruited and completed a questionnaire on their medical history and lifestyle factors...
March 8, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28273365/metformin-attenuates-renal-fibrosis-in-both-ampk%C3%AE-2-dependent-and-independent-manners
#8
Yenan Feng, Shuaixing Wang, Youyi Zhang, Han Xiao
Metformin is a well-known AMP-activated protein kinase (AMPK) activator, and it has been shown to inhibit organ fibrosis. Whether AMPKα2 mediates metformin protection against renal fibrosis remains unknown. Here, we aimed to investigate the role of the AMPKα2 isoform in mediating the inhibitory effect of metformin on renal fibrosis. Unilateral ureteral obstruction (UUO) was used to induce renal fibrosis in wild-type (WT) and AMPKα2 knockout (AMPKα2(-/-) ) mice. Metformin treatment was initiated 3 days before UUO and was continued until 7 days after UUO...
March 8, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28271563/gastric-cancer-managment-kinases-as-a-target-therapy
#9
Batoul Farran, Susanne Müller, Raquel C Montenegro
The molecular diagnostics revolution has reshaped the practice of oncology by facilitating the identification of genetic, epigenetic and proteomic modifications correlated with cancer, thus delineating 'oncomaps' for various cancer types. These advances have enhanced our understanding of gastric cancer, one of the most fatal diseases worldwide, and culminated in the approval of novel molecular therapies such as trastuzumab. Gastric tumours display recurrent aberrations in key kinase oncogenes such as Her2, EGFR, PI3K, mTOR or c-Met, suggesting that these receptors are amenable to inhibition using specific drug agents...
March 7, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28267873/changes-in-ppar%C3%AE-expression-in-a-rat-model-of-stress-induced-depression
#10
Keng-Fan Liu, Yingxiao Li, Kai-Chung Cheng, Chao Chin Hsu, Juei-Tang Cheng, Wen-Huang Peng
Depression is a common mental disorder that has been linked to a decrease in the expression of serotonin and/or the serotonin transporter in the brain. Antidepressants that target the monoaminergic system are widely used in the clinical setting. PPARδ overexpression or activation is thought to improve depression-like behaviors in rodents. The present study was designed to characterize the changes in PPARδ expression in the hippocampus in rats with stress-induced depression. We used an unpredictable chronic mild stress (CMS) model in rats to study the role of PPARδ in the hippocampus...
March 7, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28261855/inpp4b-overexpression-suppresses-migration-invasion-and-angiogenesis-of-human-prostate-cancer-cells
#11
Haiwen Chen, Hongliang Li, Qi Chen
Inositol polyphosphate 4-phosphatase B (INPP4B) has been identified as a tumor suppressor in different human cancers. However, the role of INPP4B in the angiogenesis of human prostate cancer cells remains unclear. In this study, we first compared the expression of INPP4B between prostate cancer tissues and tumor-adjacent normal prostate tissues using immunohistochemistry. Then, we explored the role of INPP4B in prostate cancer progression via transfection of a Flag-INPP4B plasmid into PC3 and DU145 cells in vitro and in vivo...
March 6, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28261854/oligog-cf-5-20-normalizes-cystic-fibrosis-mucus-by-chelating-calcium
#12
Anna Ermund, Christian V Recktenwald, Gudmund Skjåk-Braek, Lauren N Meiss, Edvar Onsøyen, Philip D Rye, Arne Dessen, Astrid Hilde Myrset, Gunnar C Hansson
The goal of this study was to determine whether the guluronate (G) rich alginate OligoG CF-5/20 (OligoG) could detach cystic fibrosis (CF) mucus by calcium chelation, which is also required for normal mucin unfolding. Since bicarbonate secretion is impaired in CF, leading to insufficient mucin unfolding and thereby attached mucus and since bicarbonate has the ability to bind calcium, we hypothesized that the calcium chelating property of OligoG would lead to detachment of CF mucus. Indeed, OligoG could compete with the N-terminus of the MUC2 mucin for calcium binding as shown by microscale thermophoresis...
March 6, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28251688/inhibition-of-aldh2-protects-pc12-cells-against-formaldehyde-induced-cytotoxicity-involving-the-protection-of-hydrogen-sulfide
#13
Ying Chen, Cheng-Fang Zhou, Fan Xiao, Hong-Lin Huang, Ping Zhang, Hong-Feng Gu, Xiao-Qing Tang
Formaldehyde (FA), a common environmental contaminant, has toxic effects on the central nervous system (CNS). We have previously found that hydrogen sulfide (H2 S), the third endogenous gaseous mediator, protects neuron against the toxicity of FA. However, the underlying mechanism is poor. Aldehyde-dehydrogenase-2 (ALDH2) plays a major role in detoxification of reactive aldehyde in a range of organs and cell types. Therefore, we speculated that H2 S antagonizes FA-induced neurotoxicity by modulating ALDH2. In the present study, we found that the exposure of PC12 cells to FA causes increase in ALDH2 expression and activity...
March 2, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28251683/limb-remote-ischemic-postconditioning-induced-elevation-of-fibulin-5-confers-neuroprotection-to-rats-with-cerebral-ischemia-reperfusion-injury-activation-of-the-akt-pathway
#14
Wei Zhang, Ye Wang, Guorong Bi
Limb remote ischemic postconditioning (RIPostC) is an effective and well-acknowledged treatment for brain ischemia injury. The present study aimed to evaluate the role of fibulin-5 in the neuroprotection of RIPostC against cerebral ischemia/reperfusion (I/R) injury in rats. The middle cerebral artery occlusion (MCAO) model was established in rats and then RIPostC was carried out by 3 cycles of 10 min occlusion/10 min release of the bilateral femoral artery at the beginning of the reperfusion. To downregulate the fibulin-5 level, fibulin-5 siRNA was injected into the lateral ventricle 24 h before MCAO...
March 2, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28222218/reduced-inflammatory-responses-of-follicular-helper-t-cell-promote-the-development-of-regulatory-b-cells-after-roux-en-y-gastric-bypass
#15
Junfang Zhan, Liyu Huang, Haiyong Ma, Huan Chen, Yuan Yang, Sheng Tan, Wendy Song, Weiguo Zhao, Xiaojiang Dai
Bariatric surgery is currently the most effective strategy in treating severe obesity and its comorbidities, such as type 2 diabetes (T2D). However, the mechanism through which bariatric surgery mediates its benefits is not completely understood. Since obesity and T2D represent yet another inflammatory disease, and follicular helper T (Tfh) cells play important roles in inflammatory disorders, we investigated whether the Tfh activity was altered after Roux-en-Y gastric bypass (RYGB), one of the most common bariatric surgery procedures...
February 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28218955/antihyperglycemiac-action-of-diosmin-a-citrus-flavonoid-is-induced-through-endogenous-%C3%AE-endorphin-in-type-i-like-diabetic-rats
#16
Chia-Chen Hsu, Mang Hung Lin, Juei Tang Cheng, Ming Chang Wu
Diosmin is one of the flavonoids contained in citrus and has been demonstrated to improve glucose metabolism in diabetic disorders. However, the mechanism(s) of diosmin in glucose regulation remain obscure. Therefore, we investigated the potential mechanism(s) for the antihyperglycemic action of diosmin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Diosmin lowered hyperglycemia in a dose-dependent manner in STZ-diabetic rats. This action was inhibited by naloxone at a dose sufficient to block opioid receptors...
February 20, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28199751/impact-of-polymorphisms-in-angiogenesis-related-genes-on-clinical-outcomes-of-radiotherapy-in-patients-with-nasopharyngeal-carcinoma
#17
Wan-Le Ma, Rong Liu, Li-Hua Huang, Chan Zou, Jie Huang, Jing Wang, Shao-Jun Chen, Xiang-Guang Meng, Jing-Ke Yang, Han Li, Guo-Ping Yang, Cheng-Xian Guo
PURPOSE: To assess the relationship between gene polymorphism in angiogenesis-related genes and radiation responses in nasopharyngeal carcinoma (NPC) patients. METHODS: The genotypes of 180 NPC patients were analyzed by Sequenom MassARRAY. The Response Evaluation Criteria in Solid Tumors were used for assessing efficacies. And The criteria of Radiation Therapy Oncology Group or European Organization for Research & Treatment of Cancer were utilized for evaluating acute toxic reactions in response to radiation...
February 15, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28135768/population-pharmacokinetics-analysis-of-intravenous-busulfan-in-chinese-patients-undergoing-hematopoietic-stem-cell-transplantation
#18
Xuemei Wu, Helin Xie, Weiwei Lin, Ting Yang, Nainong Li, Shanshan Lin, Xiaohong Yuan, Jinhua Ren, Xiaofan Li, Xian Huang
There are several reports describing population pharmacokinetic (popPK) models of busulfan (BU). However, limited information is available in Chinese hematopoietic stem-cell transplantation (HSCT) patients. The present study aimed to establish a popPK model of intravenous BU in Chinese HSCT patients for individualized drug therapy. The popPK model of BU was developed from a total of 284 concentration-time points from 53 patients. The effects of demographic and biochemical covariates were investigated by NONMEM(®) software...
January 30, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28135761/palmitoleic-acid-reduces-the-inflammation-in-lps-stimulated-macrophages-by-inhibition-of-nf%C3%AE%C2%BAb-independently-of-ppars
#19
Camila O Souza, Alexandre A S Teixeira, Luana A Biondo, Loreana S Silveira, Philip Calder, José C Rosa Neto
Palmitoleic acid (PM, 16:1n-7) has anti-inflammatory properties that could be linked to higher expression of PPARα, an inhibitor of NFκB. Macrophages play a major role in the pathogenesis of chronic inflammation, however, the effects of PM on macrophages are underexplored. Thus, we aimed to investigate the effects of PM in activated macrophages as well the role of PPARα. Primary macrophages were isolated from C57BL6 (WT) and PPARα knockout (KO) mice, cultured under standard conditions and exposed to LPS (2...
January 30, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28109180/the-intrauterine-renin-angiotensin-system-sex-specific-effects-on-the-prevalence-of-spontaneous-preterm-birth
#20
Kirsty G Pringle, Tamas Zakar, Eugenie R Lumbers
Preterm birth (PTB) is the single largest cause of death in infants and young children. The rate of PTB is significantly higher in male infants, particularly those that are born very preterm. Here we present evidence to suggest that the decidual renin-angiotensin system may play a role in inhibiting inflammation and maintaining the integrity of the fetal membranes during pregnancy, and that sex-specific alterations in the intrauterine RAS could contribute to the increased risk of PTB in male babies. Women carrying female fetuses have high levels of expression of decidual prorenin at term...
January 21, 2017: Clinical and Experimental Pharmacology & Physiology
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