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British Journal of Pharmacology

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
Ning Xia, Huige Li
Under physiological conditions, perivascular adipose tissue (PVAT) attenuates agonist-induced vasoconstriction by releasing vasoactive molecules including hydrogen peroxide, angiotensin 1-7, adiponectin, methyl palmitate, hydrogen sulfide, nitric oxide (NO) and leptin. This anticontractile function of PVAT is lost under conditions of obesity. The central mechanism underlying PVAT dysfunction in obesity is likely to be an "obesity triad" (consisting of PVAT hypoxia, inflammation and oxidative stress) that leads to dysregulation of PVAT-derived vasoregulators...
October 20, 2016: British Journal of Pharmacology
Mengmeng Wang, Amanda K Kussrow, Mireia Fernandez Ocana, Jeffrey R Chabot, Christopher S Lepsy, Darryl J Bornhop, Denise M O'Hara
BACKGROUND AND PURPOSE: A monoclonal antibody (PF-00547659) against Mucosal Adressin Cell Adhesion Molecule (MAdCAM), expressed as both soluble (sMAdCAM) and trans-membrane (mMAdCAM) target forms, showed over 30-fold difference in antibody-target KD between in vitro (Biacore) and clinically derived (KD,in-vivo ) values. Back-scattering interferometry (BSI) was applied to acquire physiologically relevant KD values which were used to establish in vitro and in vivo correlation (IVIVC). EXPERIMENTAL APPROACH: Back-scattering interferometry (BSI) was applied to obtain KD values between PF-00547659 and recombinant human MAdCAM in buffer or CHO cells and endogenous MAdCAM in human serum or colon tissue...
October 19, 2016: British Journal of Pharmacology
Raquel Tonello, Camilla Fusi, Serena Materazzi, Ilaria M Marone, Francesco De Logu, Silvia Benemei, Muryel C Gonçalves, Elisabetta Coppi, Celio J Castro-Junior, Marcus Vinicius Gomez, Pierangelo Geppetti, Juliano Ferreira, Romina Nassini
BACKGROUND AND PURPOSE: Peptides from venomous animals have long been important tools for understanding pain mechanisms and for the discovery of pain treatments. Here, we hypothesized that Phα1β, a peptide purified from the armed spider Phoneutria nigriventer venom, produces analgesia by blocking the transient receptor potential ankyrin 1 (TRPA1) channel. EXPERIMENTAL APPROACH: Cultured rat dorsal root ganglion (DRG) neurons, human IMR90 fibroblasts or HEK293 cells expressing the human TRPA1 (hTRPA1-HEK293), TRPV1 (hTRPV1-HEK293) or TRPV4 (hTRPV4-HEK293), were used for calcium imaging and electrophysiology...
October 19, 2016: British Journal of Pharmacology
Sharon L I Wong, Maria B Sukkar
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein which regulates interactions between cells and their surrounding extracellular matrix (ECM), and thus governs fundamental cellular functions such as cell adhesion, proliferation and differentiation. SPARC also regulates the expression and activity of numerous growth factors and matrix metalloproteinases essential for ECM degradation and turnover. Studies in SPARC-null mice have revealed a critical role for SPARC in tissue development, injury and repair, and in the regulation of the immune response...
October 19, 2016: British Journal of Pharmacology
Wei Hu, Zhiqiang Ma, Shouyin Di, Shuai Jiang, Yue Li, Chongxi Fan, Yang Yang, Dongjin Wang
The endoplasmic reticulum (ER) is an important intracellular membranous organelle. Previous studies have demonstrated that the ER is responsible for protein folding and trafficking, lipid synthesis, and the maintenance of calcium homeostasis. Interestingly, the morphology and structure of the ER were recently found to be important. Melatonin is a hormone that anticipates the daily onset of darkness in mammals, and it is well known that melatonin acts as an antioxidant by scavenging free radicals and increasing the activity of antioxidant enzymes in the body...
October 19, 2016: British Journal of Pharmacology
V Coothankandaswamy, S Cao, Y Xu, P D Prasad, P K Singh, C P Reynolds, S Yang, J Ogura, V Ganapathy, Y D Bhutia
BACKGROUND AND PURPOSE: Pancreatic cancer is an often lethal solid tumor. There is an urgent need to identify new drug targets for this disease. Highly proliferating cancer cells have an increased demand for nutrients and hence need to upregulate selective amino acid transporters. Here we wanted to find out which amino acid transporters are upregulated in pancreatic cancer and whether any of these transporters has potential as a drug target for this deadly disease. EXPERIMENTAL APPROACH: Expression of amino acid transporters in pancreatic cancer was analyzed using publicly available microarray datasets, and the findings with the transporter SLC6A14 were validated by mRNA and protein analysis...
October 17, 2016: British Journal of Pharmacology
Ilaria Peluso, Mauro Serafini
Consumption of Tea (Camellia Sinensis) has been correlated with low incidence of chronic pathologies, such as cardiovascular diseases and cancers, in which oxidative stress is deeply involved. Tea catechins and theaflavins are, respectively, the bioactive phytochemicals responsible for the antioxidant activity of Green Tea (GT) and Black Tea (BT). Apart from the redox properties, tea catechins and theaflavins could have also pharmacological activities, such as lowering effects on glucose, lipid and uric acid (UA)...
October 16, 2016: British Journal of Pharmacology
K E Zaborska, M Wareing, C Austin
The endothelium is an established modulator of vascular tone; however the recent discovery of the anti-contractile nature of perivascular adipose tissue (PVAT) suggests that the fat which surrounds many blood vessels can also modulate vascular tone. Both the endothelium and PVAT secrete vasoactive substances, which regulate vascular function. Many of these factors are common to both the endothelium and PVAT; therefore, this review will highlight the potential shared mechanisms in modulation of vascular tone...
October 16, 2016: British Journal of Pharmacology
Ivonne M C M Rietjens, Jochem Louisse, Karsten Beekmann
Phytoestrogens are plant-derived dietary compounds with structural similarity to 17-β-estradiol (E2), the primary female sex hormone. This structural similarity to E2 enables phytoestrogens to cause (anti)estrogenic effects by binding to the estrogen receptors. The aim of the present review is to present a state-of-the-art overview of the the potential health effects of dietary phytoestrogens. Various beneficial health effects have been ascribed to phytoestrogens, such as a lowered risk on menopausal symptoms like hot flushes and osteoporosis, lowered risks on cardiovascular disease, obesity, metabolic syndrome and type 2 diabetes, brain function disorders, breast cancer, prostate cancer, bowel cancer and other cancers...
October 9, 2016: British Journal of Pharmacology
Isabel López-García, Domokos Gerő, Bartosz Szczesny, Petra Szoleczky, Gabor Olah, Katalin Módis, Kangling Zhang, Gao Jungling, Ping Wu, Lawrence C Sowers, Doug DeWitt, Donald S Prough, Csaba Szabo
BACKGROUND AND PURPOSE: We hypothesized that an in vitro, stretch-based model of neural injury may be useful to identify compounds that decrease the cellular damage in neurotrauma. EXPERIMENTAL APPROACH: We screened three neural cell lines (B35, RN33B, SH-SY5Y) subjected to two differentiation methods and selected all-trans-retinoic acid-differentiated B35 rat neuroblastoma cells subjected to rapid stretch injury, coupled with a subthreshold concentration of H2 O2 , for the screen...
October 9, 2016: British Journal of Pharmacology
Charles W Schindler, Eric B Thorndike, Masaki Suzuki, Kenner C Rice, Michael H Baumann
BACKGROUND AND PURPOSE: 3,4-Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone with stimulatory cardiovascular effects that can lead to serious medical complications. Here we examined the pharmacological mechanisms underlying these cardiovascular actions of MDPV in conscious rats. EXPERIMENTAL APPROACH: Male Sprague-Dawley rats had telemetry transmitters surgically implanted for the measurement of blood pressure (BP) and heart rate (HR). On test days, rats were placed individually in standard isolation cubicles...
October 7, 2016: British Journal of Pharmacology
Balazs T Nemeth, Zoltan V Varga, Wen Jin Wu, Pal Pacher
Epidermal growth factor receptor-2 (HER-2) is overexpressed in 20% to 25% of human breast cancers, which is associated with aggressive tumor growth and poor prognosis. Trastuzumab (Herceptin®) is a humanized monoclonal antibody directed against HER-2, the first highly selective form of therapy targeting HER-2 overexpressing tumors. Although initial trials indicated high efficacy and a favorable safety profile of the drug, the first large, randomized trial prompted a retrospective analysis of cardiac dysfunction in prior trials utilizing trastuzumab...
October 7, 2016: British Journal of Pharmacology
Maria Domenica Sanna, Laura Lucarini, Mariaconcetta Durante, Carla Ghelardini, Emanuela Masini, Nicoletta Galeotti
BACKGROUND AND PURPOSE: Neuropathic pain is undertreated, with a large detrimental effect on quality of life, partly because of low treatment efficacy, but also because pathophysiological mechanisms are not fully elucidated. To better clarify the pathobiology of neuropathic pain, the presence of neuroinflammation and oxidative stress was investigated in a model of peripheral neuropathy. In search of an innovative treatment for neuropathic pain, our research investigated the effects of histamine H4 receptor (H4 R) modulation...
October 7, 2016: British Journal of Pharmacology
K Sugahara, Y Maeda, K Shimano, A Mogami, H Kataoka, K Ogawa, K Hikida, H Kumagai, M Asayama, T Yamamoto, T Harada, P Ni, S Inoue, A Kawaguchi
BACKGROUND AND PURPOSE: We conducted preclinical and clinical studies to examine the pharmacological, particularly cardiac, effects of amiselimod (MT-1303), a second-generation sphingosine 1-phosphate (S1P) receptor modulator, designed to reduce the bradycardia effects associated with fingolimod and other S1P receptor modulators. EXPERIMENTAL APPROACH: The selectivity of the active metabolite amiselimod phosphate (amiselimod-P) for human S1P receptors and activation of the G-protein-coupled inwardly rectifying potassium (GIRK) channel in human atrial myocytes were assessed...
October 7, 2016: British Journal of Pharmacology
Rachel M McQuade, Simona E Carbone, Vanesa Stojanovska, Ahmed Rahman, Rachel M Gwynne, Ainsley M Robinson, Craig A Goodman, Joel C Bornstein, Kulmira Nurgali
BACKGROUND AND PURPOSE: Oxaliplatin is a platinum-based chemotherapeutic drug used as a first-line therapy for colorectal cancer. However, its use is associated with severe gastrointestinal side-effects resulting in dose limitations and/or cessation of treatment. In this study, we tested whether oxidative stress, caused by chronic oxaliplatin treatment, induces enteric neuronal damage and colonic dysmotility EXPERIMENTAL APPROACH: Oxaliplatin (3 mg/kg/d) was administered in vivo to Balb/c mice intraperitoneally three times a week...
October 7, 2016: British Journal of Pharmacology
Xueting Bai, Peixuan Yang, Qiaoling Zhou, Bozhi Cai, Manon Buist-Homan, He Cheng, Jiyang Jiang, Daifei Shen, Lijun Li, Xiajiong Luo, Klaas Nico Faber, Han Moshage, Ganggang Shi
BACKGROUND AND PURPOSE: Liver diseases are mostly accompanied by inflammation and hepatocyte death. Therapeutic approaches targeting both hepatocyte injury and inflammation are not available. Natural compounds are considered as potential treatment for inflammatory liver diseases. Hesperetin, a flavonoid component of citrus fruits has been reported to have anti-inflammatory properties. The aim of this study was to evaluate the cytoprotective and anti-inflammatory properties of hesperetin both in vitro and in models of fulminant hepatitis...
October 7, 2016: British Journal of Pharmacology
Diego Currò, Gianluca Ianiro, Silvia Pecere, Stefano Bibbò, Giovanni Cammarota
Functional bowel disorders (FBDs), mainly irritable bowel syndrome (IBS) and functional constipation (FC, also called chronic idiopathic constipation), are highly diffused worldwide. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, although less common, has a strong impact on patients' quality of life, as well as is highly expensive for our healthcare. A definite cure for those disorders is still yet to come. Over the years, several therapeutic approaches complementary or alternative to traditional pharmacological treatments, including probiotics, prebiotics, synbiotics, fiber and herbal medicinal products, have been investigated for the management of both groups of diseases...
October 3, 2016: British Journal of Pharmacology
Antonello Santini, Ettore Novellino
Growing attention is nowadays given to the possible preventive/alternative ways to avoid illness onset. Lifestyle change and proper food habits are taking over the conventional pharmaceutical based approach especially for chronic pathologies. Nutraceuticals propose themselves as a key tool to prevent and cure some pathologic conditions. This is leading the research to develop new formulations based on these pharma-foods addressed in a specific way to prevent and cure health issues, which, in turn, will have an impact on the therapy-related cost to be sustained by any National Health Organization...
September 29, 2016: British Journal of Pharmacology
Raffaele Simeoli, Giuseppina Mattace Raso, Claudio Pirozzi, Adriano Lama, Anna Santoro, Roberto Russo, Trinidad Montero-Melendez, Roberto Berni Canani, Antonio Calignano, Mauro Perretti, Rosaria Meli
BACKGROUND AND PURPOSE: Butyrate has shown benefits in inflammatory bowel diseases (IBD). However, its oral administration is infrequent due to rancid smell and unpleasant taste. The efficacy of a more palatable butyrate-releasing derivative, N-(1-carbamoyl-2-phenylethyl) butyramide (FBA), was evaluated in a mouse model of colitis induced by dextran sodium sulphate (DSS). EXPERIMENTAL APPROACH: Male 10-week-old BALB/c mice received DSS (2.5%) in drinking water (for 5d) followed by DSS-free water for 7d (DSS group)...
September 29, 2016: British Journal of Pharmacology
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