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British Journal of Pharmacology

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https://www.readbyqxmd.com/read/27891602/cannabimimetic-phytochemicals-in-the-diet-an-evolutionary-link-to-food-selection-and-metabolic-stress-adaptation
#1
REVIEW
Jürg Gertsch
The endocannabinoid system (ECS) is a major lipid signaling network that plays important pro-homeostatic (allostatic) roles not only in the nervous system but in peripheral organs. Increasing evidence points towards a dietary component in the modulation of the ECS. Cannabinoid receptors in hominids co-evolved with diet and the ECS constitutes a feedback loop for food selection and energy metabolism. Here it is postulated that the mismatch of ancient lipid genes of hunter-gatheres and pastoralists with the high carbohydrate diet introduced by agriculture could be compensated via dietary modulation of the ECS...
November 27, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27886373/clemizole-hydrochloride-blocks-cardiac-potassium-currents-stably-expressed-in-hek-293-cells
#2
Ling-Jun Jie, Wei-Yin Wu, Gang Li, Guo-Sheng Xiao, Shetuan Zhang, Gui-Rong Li, Yan Wang
BACKGROUND AND PURPOSE: Recent studies showed that clemizole has a potential therapeutic effect for hepatitis C infection and also potently inhibits TRPC5 channels. The aim of the present study was to investigate whether clemizole blocks cardiac K(+) currents and affects cardiac repolarization. EXPERIMENTAL APPROACH: Whole-cell patch technique was employed to examine the effects of clemizole on hERG channel current, IKs and Kv1.5 current in HEK 293 cell expression systems as well as on ventricular action potentials of guinea pig hearts...
November 25, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27882550/investigating-interactions-between-epicardial-adipose-tissue-and-cardiac-myocytes-what-can-we-learn-from-different-approaches
#3
REVIEW
Katja Rietdorf, Hilary MacQueen
Heart disease is a major cause of morbidity and mortality throughout the world. Some cardiovascular conditions can be modulated by lifestyle factors such as increased exercise or a healthier diet, but many require surgical or pharmacological interventions for their management. More targeted and less invasive therapies would be beneficial. Recently it has become apparent that epicardial adipose tissue plays an important role in normal and pathological cardiac function, and it is now the focus of considerable research...
November 24, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27882538/gene-therapy-with-mesenchymal-stem-cells-expressing-ifn%C3%A3-ameliorates-neuroinflammation-in-experimental-models-of-multiple-sclerosis
#4
C Marin-Bañasco, K Benabdellah, C Melero-Jerez, B Oliver, M J Pinto-Medel, I Hurtado-Guerrero, F de Castro, D Clemente, O Fernández, F Martin, L Leyva, M Suardíaz
BACKGROUND AND PURPOSE: Recombinant IFNß is one of the first line treatments in multiple sclerosis (MS), despite its lack of efficiency in some patients. In this context, mesenchymal stem cells (MSCs) represent a promising therapeutic alternative due to their immunomodulatory properties and multipotency. Moreover, taking advantage of their pathotropism ability, these cells can be genetically modified to be used as carriers for delivering or secreting therapeutic drugs into injured tissues...
November 24, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27882537/neurochemical-and-behavioral-effects-of-hypidone-hydrochloride-yl-0919-a-novel-combined-selective-serotonin-reuptake-inhibitor-and-partial-5-ht1a-agonist
#5
Li-Ming Zhang, Xiao-Yun Wang, Nan Zhao, Yu-Lu Wang, Xiao-Xu Hu, Yu-Hua Ran, Yan-Qin Liu, You-Zhi Zhang, Ri-Fang Yang, Yun-Feng Li
The purpose of the present study was to investigate the pharmacology of hypidone hydrochloride (YL-0919), a novel selective serotonin reuptake inhibitor (SSRI) and 5-hydroxytryptamine (5-HT)1A receptor agonist with high affinity for serotonin transporter (SERT) and 5-HT1A receptors. YL-0919 promoted [(35) S]GTPγ S binding at 85% of the magnitude of the full 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), suggesting that YL-0919 is a high-efficacy partial agonist of 5-HT1A receptors...
November 24, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27864827/biomarkers-of-oxidative-and-nitro-oxidative-stress-conventional-and-novel-approaches
#6
REVIEW
Ana Cipak Gasparovic, Neven Zarkovic, Kamelija Zarkovic, Khrystyna Semen, Danylo Kaminskyy, Olha Yelisyeyeva, Serge P Bottari
The concept of oxidative stress (OS) which associates altered redox biology with various diseases was introduced thirty years ago and has generated intensive research over the past two decades. Whereas it is now commonly accepted that macromolecule oxidation in response to reactive oxygen species (ROS) is associated with a variety of pathologies, the emergence of NO as a key regulator of redox signalling has led to the discovery of the pathophysiological significance of reactive nitrogen species (RNS). RNS can elicit various modifications of macromolecules and lead to nitrative or nitro-OS...
November 19, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27864940/endogenous-lpa1-receptor-agonists-demonstrate-ligand-bias-between-calcium-and-erk-signalling-pathways-in-human-lung-fibroblasts
#7
Afrah Sattikar, Mark R Dowling, Elizabeth M Rosethorne
BACKGROUND AND PURPOSE: Human lung fibroblasts (HLF) express high levels of the LPA1 receptor, a G protein-coupled receptor (GPCR) that responds to the endogenous lipid mediator lysophosphatidic acid (1-acyl-2-hydroxy-sn-glycero-3-phosphate; LPA). Several molecular species or analogues of LPA exist and have been detected in biological fluids such as serum and plasma. The most widely expressed of the LPA receptor family is the LPA1 receptor, which predominantly couples to Gq/11 , Gi/o and G12/13 proteins...
November 16, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27864936/effect-of-sphingosine-kinase-modulators-on-interleukin-1%C3%AE-release-sphingosine-1-phosphate-receptor-1-expression-and-experimental-autoimmune-encephalomyelitis
#8
Mark Barbour, Melissa McNaughton, Stephanie D Boomkamp, Neil MacRitchie, Hui-Rong Jiang, Nigel J Pyne, Susan Pyne
BACKGROUND AND PURPOSE: The sphingosine analogue, FTY720 (Gilenya(R) ) alleviates clinical disease progression in multiple sclerosis. Here we variously assessed the effects of an azide analogue of (S)-FTY720 vinylphosphonate (compound 5; a sphingosine kinase 1 activator), (R)-FTY720 methyl ether (ROMe, a sphingosine kinase 2 inhibitor) and RB-020 (a sphingosine kinase 1 inhibitor and sphingosine kinase 2 substrate) on IL-1β formation, sphingosine 1-phosphate levels and S1P1 expression...
November 16, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27861739/afzelin-ameliorates-d-galactosamine-and-lipopolysaccharide-induced-fulminant-hepatic-failure-by-modulating-mitochondrial-quality-control-and-dynamics-150-150
#9
Sang-Bin Lee, Jung-Woo Kang, So-Jin Kim, Jongmin Ahn, Jinwoong Kim, Sun-Mee Lee
BACKGROUND AND PURPOSE: Fulminant hepatic failure (FHF) is a fatal clinical syndrome that results in excessive inflammation and hepatocyte death. Mitochondrial dysfunction is considered to be a possible mechanism of FHF. Afzelin, a flavonol glycoside found in Houttuynia cordata Thunberg, has anti-inflammatory and antioxidant properties. The present study elucidated the cytoprotective mechanisms of afzelin against D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced FHF, particularly focusing on mitochondrial quality control and dynamics...
November 15, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27861729/antidepressant-like-effects-of-fenofibrate-in-mice-via-the-hippocampal-bdnf-signaling-pathway
#10
Bo Jiang, Ying-Jie Wang, Hao Wang, Lu Song, Chao Huang, Qing Zhu, Feng Wu, Wei Zhang
BACKGROUND AND PURPOSE: Depression is a neuropsychiatric disorder accompanied by decreased brain derived neurotrophic factor (BDNF) signaling cascade in the hippocampus. Fenofibrate is a selective agonist of peroxisome proliferator-activated receptor-α (PPAR-α). In this study, we investigated the antidepressant-like effects of fenofibrate in C57BL/6 J mice. EXPERIMENTAL APPROACH: The antidepressant-like effects of fenofibrate were first detected in the forced swim test (FST) and tail suspension test (TST), and then assessed in the chronic social defeat stress (CSDS) model...
November 15, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27858997/a-novel-assay-to-assess-the-effect-of-pharmaceutical-compounds-on-the-differentiation-of-podocytes
#11
Frances Kindt, Elke Hammer, Stefan Kemnitz, Antje Blumenthal, Paul Klemm, Rabea Schlüter, Susan E Quaggin, Jens van den Brandt, Georg Fuellen, Uwe Völker, Karlhans Endlich, Nicole Endlich
BACKGROUND AND PURPOSE: Therapeutic options to treat glomerulopathies, the main cause of chronic kidney disease, are limited. Podocyte dedifferentiation is a major event in the pathogenesis of glomerulopathies. The goal of the present study was therefore to develop an assay to monitor podocyte differentiation suited for compound screening. EXPERIMENTAL APPROACH: We isolated and cultured glomeruli from transgenic mice, expressing cyan fluorescent protein (CFP) under control of the promoter of nephrin, a marker of podocyte differentiation...
November 14, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27813085/new-actions-of-an-old-friend-perivascular-adipose-tissue-s-adrenergic-mechanisms
#12
REVIEW
Nadia Ayala-Lopez, Stephanie W Watts
The revolutionary discovery in 1991 by Soltis and Cassis that perivascular adipose tissue (PVAT) has an anti-contractile effect changed how we think about the vasculature. Most experiments on vascular pharmacology begin by removing the fat surrounding the vessels. Thus, PVAT was thought of having a minor role in vascular function and present for structural support. The need to rethink our old friend PVAT's role was precipitated by observations that obesity carries a high cardiovascular risk and PVAT dysfunction occurs with obesity...
November 3, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27792844/hydrogen-peroxide-preferentially-activates-capsaicin-sensitive-high-threshold-afferents-via-trpa1-channels-in-the-guinea-pig-bladder
#13
S Nicholas, S Y Yuan, S J H Brookes, N J Spencer, V P Zagorodnyuk
BACKGROUND AND PURPOSE: There is increasing evidence suggesting that reactive oxygen species (ROS) play a major pathological role in bladder dysfunction induced by bladder inflammation and/or obstruction. The aim of this study was to determine the effect of H2 O2 on different types of bladder afferents and its mechanism of action on sensory neurons in the guinea pig bladder. EXPERIMENTAL APPROACH: "Close-to-target" single unit extracellular recordings were made from fine branches of pelvic nerves entering the guinea pig bladder, in flat sheet preparations, in vitro...
October 28, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27792834/biphasic-effects-of-propranolol-on-tumour-growth-in-b16f10-melanoma-bearing-mice
#14
Sonia Maccari, Maria Buoncervello, Andrea Rampin, Massimo Spada, Daniele Macchia, Luciana Giordani, Tonino Stati, Claudia Bearzi, Liviana Catalano, Roberto Rizzi, Lucia Gabriele, Giuseppe Marano
BACKGROUND AND PURPOSE: Propranolol is a vasoactive drug that shows antiangiogenic and antitumour activities in melanoma. However, it is unknown whether these activities are dose-dependent and whether there is a relationship between systemic vascular effects of propranolol and anti-melanoma activity. EXPERIMENTAL APPROACH: Effects of increasing doses of propranolol (10, 20, 30 and 40 mg·kg(-1) ·day(-1) ) on tumour growth were studied in B16F10 melanoma-bearing mice...
October 28, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27784136/the-role-of-apolipoprotein-n-acyl-transferase-lnt-in-the-lipidation-of-factor-h-binding-protein-of-neisseria-meningitidis-strain-mc58-and-its-potential-as-a-drug-target
#15
Rag da Silva, C P Churchward, A V Karlyshev, O Eleftheriadou, A K Snabaitis, M R Longman, A Ryan, R Griffin
BACKGROUND AND PURPOSE: The level of cell surface expression of the meningococcal vaccine antigen, Factor H binding protein (FHbp) varies between and within strains and this limits the breadth of strains that can be targeted by FHbp-based vaccines. The molecular pathway dictating expression of FHbp at the cell surface, including its lipidation, sorting to the outer membrane and export, and the potential regulation of this pathway have not been investigated until now. This knowledge will aid our evaluation of FHbp vaccines...
October 26, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27774624/bet-bromodomain-suppression-inhibits-vascular-inflammation-by-blocking-nf-%C3%AE%C2%BAb-and-mapk-activation
#16
Mingcheng Huang, Shan Zeng, Yaoyao Zou, Maohua Shi, Qian Qiu, Youjun Xiao, Guoqiang Chen, Xiuyan Yang, Liuqin Liang, Hanshi Xu
BACKGROUND AND PURPOSE: Increasing evidence indicates the critical role of bromodomain and extra-terminal domain (BET) proteins in regulating immune and inflammatory responses, however, their contribution to vascular inflammation remains to be defined. In this study, we investigated the effect of BET bromodomain inhibition on regulating vascular inflammation and the underlying mechanisms. EXPERIMENTAL APPROACH: Human umbilical vein endothelial cells (HUVECs) were isolated from fresh umbilical cords...
October 24, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27774604/distribution-physiology-and-pharmacology-of-relaxin-3-rxfp3-systems-in-brain
#17
Sherie Ma, Craig M Smith, Anna Blasiak, Andrew L Gundlach
Relaxin-3 is a member of a superfamily of structurally-related peptides that includes relaxin and insulin-like peptide hormones. Soon after the discovery of the relaxin-3 gene, relaxin-3 was identified as an abundant neuropeptide in brain with a distinctive topographical distribution within a small number of GABA neuron populations that is well conserved across species. Relaxin-3 is thought to exert its biological actions through a single class-A GPCR - relaxin-family peptide receptor 3 (RXFP3). Class-A comprises GPCRs for relaxin-3 and insulin-like peptide-5 and other peptides such as orexin and the monoamine transmitters...
October 23, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27771943/synaptic-zn-2-and-febrile-seizure-susceptibility
#18
Christopher A Reid, Michael S Hildebrand, Saul A Mullen, Joanne M Hildebrand, Samuel F Berkovic, Steven Petrou
Zn(2+) , the second most prevalent trace element in the body, is essential for supporting a wide range of biological functions. While the majority of Zn(2+) in the brain is protein-bound, a significant proportion of free Zn(2+) is found co-localized with glutamate in synaptic vesicles and is released in an activity-dependent manner. Clinical studies have shown Zn(2+) levels are significantly lower in blood and cerebrospinal fluid of children that suffer febrile seizures. Likewise, investigations in multiple animal models demonstrate that low levels of brain Zn(2+) increase seizure susceptibility...
October 23, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27771940/synthetic-non-peptide-low-molecular-weight-agonists-of-the-relaxin-receptor-1
#19
REVIEW
Alexander I Agoulnik, Irina U Agoulnik, Xin Hu, Juan Marugan
Relaxin is a small heterodimeric peptide hormone of the insulin/relaxin superfamily produced mainly in female and male reproductive organs. It has potent antifibrotic, vasodilatory and angiogenic effects and regulates the normal function of various physiological systems. Preclinical studies and recent clinical trials have shown the promise of recombinant relaxin as a therapeutic agent in the treatment of cardiovascular and fibrotic diseases. However, there are the universal drawbacks of peptide-based pharmacology that apply to relaxin: a short half-life in vivo requires its continuous delivery, and there are high costs of production, storage and treatment, as well as the possibility of immune responses...
October 23, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27764525/celastrol-prevents-cadmium-induced-neuronal-cell-death-by-blocking-mitochondrial-ros-inactivation-of-ampk-and-activation-of-mtor-pathway
#20
Ruijie Zhang, Nana Zhang, Hai Zhang, Chunxiao Liu, Xiaoqing Dong, Xiaoxue Wang, Yu Zhu, Chong Xu, Lei Liu, Sijun Yang, Shile Huang, Long Chen
BACKGROUND AND PURPOSE: Increasing evidence has suggested cadmium (Cd), as an inducer of reactive oxygen species (ROS), is a potential pathogenic factor in human neurodegenerative diseases. Thus, it is important to find effective interventions for Cd-induced oxidative stress in the central nervous system. The purpose of this study was to determine whether and how celastrol, a plant-derived triterpene, could mitigate Cd-induced ROS and cell death in neuronal cells. EXPERIMENTAL APPROACH: PC12, SH-SY5Y cells and primary murine neurons were chosen as a model to study celastrol neuroprotection against Cd-poisoning...
October 20, 2016: British Journal of Pharmacology
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