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Pharmacological Research: the Official Journal of the Italian Pharmacological Society

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https://www.readbyqxmd.com/read/28532817/-pro-renin-receptor-as-a-therapeutic-target-for-the-treatment-of-cardiovascular-diseases
#1
REVIEW
Yuan Sun, A H Jan Danser, Xifeng Lu
The discovery of the (pro)renin receptor [(P)RR] 15years ago stimulated ideas on prorenin being more than renin's inactive precursor. Indeed, binding of prorenin to the (P)RR induces a conformational change in the prorenin molecule, allowing it to display angiotensin-generating activity, and additionally results in intracellular signaling in an angiotensin-independent manner. However, the prorenin levels required to observe these angiotensin-dependent and -independent effects of the (P)RR are many orders above its in vivo concentrations, both under normal and pathological conditions...
May 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28532816/obesity-and-hypertension
#2
REVIEW
Gino Seravalle, Guido Grassi
No abstract text is available yet for this article.
May 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28527699/at1-receptor-signaling-pathways-in-the-cardiovascular-system
#3
REVIEW
Tatsuo Kawai, Steven J Forrester, Shannon O'Brien, Ariele Baggett, Victor Rizzo, Satoru Eguchi
The importance of the renin angiotensin aldosterone system in cardiovascular physiology and pathophysiology has been well described whereas the detailed molecular mechanisms remain elusive. The angiotensin II type 1 receptor (AT1 receptor) is one of the key players in the renin angiotensin aldosterone system. The AT1 receptor promotes various intracellular signaling pathways resulting in hypertension, endothelial dysfunction, vascular remodeling and end organ damage. Accumulating evidence shows the complex picture of AT1 receptor-mediated signaling; AT1 receptor-mediated heterotrimeric G protein-dependent signaling, transactivation of growth factor receptors, NADPH oxidase and ROS signaling, G protein-independent signaling, including the β-arrestin signals and interaction with several AT1 receptor interacting proteins...
May 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28511989/biased-agonism-antagonism-at-the-angii-at1-receptor-implications-for-adrenal-aldosterone-production-and-cardiovascular-therapy
#4
REVIEW
Jennifer Maning, Shmuel Negussie, Michelle A Clark, Anastasios Lymperopoulos
Many of the effects of angiotensin II (AngII), including adrenocortical aldosterone release, are mediated by the AngII type 1 receptor (AT1R), a receptor with essential roles in cardiovascular homeostasis. AT1R belongs to the G protein-coupled receptor (GPCR) superfamily, mainly coupling to the Gq/11 type of G proteins. However, it also signals through βarrestins, oftentimes in parallel to eliciting G protein-dependent signaling. This has spurred infinite possibilities for cardiovascular pharmacology, since various beneficial effects are purportedly exerted by AT1R via βarrestins, unlike AT1R-induced G protein-mediated pathways that usually result in damaging cardiovascular effects, including hypertension and aldosterone elevation...
May 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28511988/exploring-the-potential-of-nanotherapeutics-in-targeting-tumor-microenvironment-for-cancer-therapy
#5
REVIEW
Eameema Muntimadugu, Nagavendra Kommineni, Wahid Khan
Advanced research in the field of cancer biology clearly demonstrated the key role of tumor microenvironment (TME) in cancer development and metastasis particularly in solid tumors. Components of TME, being non-neoplastic in nature provide supportive and permissive conditions for the growth of cancer cells. Hence it is important to modify TME in cancer therapy and this would be achieved by better understanding of TME morphological features and functioning of stromal components. Nanotechnology based drug delivery offers various advantages such as prolonged circulation time, delivery of cargo at desired site, improved bioavailability, reduced toxicity etc...
May 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28506796/from-head-to-toe-sex-and-gender-differences-in-the-treatment-of-ischemic-cerebral-disease
#6
REVIEW
Lorenzo Falsetti, Giovanna Viticchi, Laura Buratti, Clotilde Balucani, Alberto M Marra, Mauro Silvestrini
Stroke is a major cause of mortality and morbidity, particularly in the older ages. Women have a longer life expectancy and are more likely to experience stroke than men. Interestingly, the increased risk of ischemic stroke in women seems to be independent from age or classical cardiovascular risk factors. Notwithstanding the fact that stroke outcomes and survival are usually poorer in women, current evidence suggests that thrombolysis, antiplatelet and anticoagulant therapies are more beneficial in women than in men...
May 12, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28501518/cannabidiol-in-medical-marijuana-research-vistas-and-potential-opportunities
#7
REVIEW
Carola Rong, Yena Lee, Nicole E Carmona, Danielle S Cha, Renee-Marie Ragguett, Joshua D Rosenblat, Rodrigo B Mansur, Roger C Ho, Roger S McIntyre
The high and increasing prevalence of medical marijuana consumption in the general population invites the need for quality evidence regarding its safety and efficacy. Herein, we synthesize extant literature pertaining to the phytocannabinoid cannabidiol (CBD) and its brain effects. The principle phytocannabinoid Δ(9)-tetrahydrocannabinol (Δ(9)-THC) and CBD are the major pharmacologically active cannabinoids. The effect of CBD on brain systems as well as on phenomenological measures (e.g. cognitive function) are distinct and in many cases opposite to that of Δ(9)-THC...
May 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28501517/nanoparticles-for-modulating-tumor-microenvironment-to-improve-drug-delivery-and-tumor-therapy
#8
REVIEW
Shu Yang, Huile Gao
Tumor microenvironment (TME) plays a critical role in tumorigenesis, tumor invasion and metastasis. TME is composed of stroma, endothelial cells, pericytes, fibroblasts, smooth muscle cells, and immune cells, which is characterized by hypoxia, acidosis, and high interstitial fluid pressure. Due to the important role of TME, we firstly reviewed the composition of TME and discussed the impact of TME on tumor progression, drug and nanoparticle delivery. Next, we reviewed current strategies developed to modulate TME, including modulating tumor vasculature permeability, tumor associated macrophage phenotypes, tumor associated fibroblasts, tumor stroma components, tumor hypoxia, and multiple interventions simultaneously...
May 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28501516/is-dual-inhibition-of-metalloenzymes-hdac-8-and-mmp-2-a-potential-pharmacological-target-to-combat-hematological-malignancies
#9
REVIEW
Sk Abdul Amin, Nilanjan Adhikari, Tarun Jha
For the last three decades, metalloenzymes such as histone deacetylases (HDACs) and matrix metalloproteinases (MMPs) have been identified in promoting solid as well as hematological carcinogenesis. Histone deacetylase 8 (HDAC-8), a class I HDAC enzyme, may serve as 'epigenetic player' that affects in the regulation of transcription factors and alters the structure of chromosome associated with tumorigenesis. It is established that the influence of MMP-2 in invasion, metastasis and angiogenenic events of hematological malignancies may be suppressed by HDAC inhibitors through reversion-inducing-cysteine-rich protein with kazal motifs (RECK) protein...
May 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28495658/genomics-of-hypertension
#10
Sandosh Padmanabhan, Alisha Aman, Anna F Dominiczak
A complex network of interacting pathways involving renal, neural, endocrine, vascular and other mechanisms controls the main determinants of blood pressure - cardiac output and total peripheral resistance. Multiple genes within each of these systems contribute to the specialized functions regulating blood pressure. The monogenic forms of blood pressure dysregulation have provided valuable insights into blood pressure regulation and expanded our understanding of both the mechanisms and the treatment of hypertension...
May 8, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28495657/outer-membrane-vesicles-extracted-from-neisseria-meningitidis-serogroup-x-for-prevention-of-meningococcal-disease-in-africa
#11
Reinaldo Acevedo, Caridad Zayas, Gunnstein Norheim, Sonsire Fernández, Barbara Cedré, Yisabel Aranguren, Maribel Cuello, Yaimara Rodriguez, Humberto González, Aleida Mandiarote, Marylin Pérez, Maritza Hernández, Mabel Hernández-Cedeño, Domingo González, Sverre-Henning Brorson, Einar Rosenqvist, Lisbeth Naess, Gro Tunheim, Daniel Cardoso, Luis García
Meningococcal disease is caused mainly by serogroups A, B, C, Y, W of N. meningitidis. However, numerous cases of meningitis caused by serogroup X N. meningitidis (MenX) have recently been reported in several African countries. Currently, there are no licensed vaccines against this pathogen and most of the MenX cases have been caused by meningococci from clonal complex (c.c) 181. Detergent extracted meningococcal outer membrane vesicle (dOMV) vaccines have previously shown to be safe and effective against epidemics of serogroup B meningococcal disease in all age groups...
May 8, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28483479/sulfuretin-has-therapeutic-activity-against-acquired-lymphedema-by-reducing-adipogenesis
#12
Kangsan Roh, Suji Kim, Hee Kang, Jin-Mo Ku, Kye Won Park, Sukchan Lee
Acquired lymphedema is a pathological condition associated with lymphatic dysfunction caused by surgical treatments for cancer. Although global estimates of the prevalence of acquired lymphedema have been rising, there are currently no effective therapeutics available. Since adipose tissue accumulation is a clinical hallmark of lymphedema, we hypothesized that regulation of adipogenesis in lymphedematous tissue could be used as a therapeutic intervention against lymphedema. Toward this, we investigated the possibility of anti-adipogenic 30% ethanol Rhus verniciflua Stokes (RVS) extract as a potential lymphedema treatment...
May 5, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28479371/udp-glucuronosyltransferases-ugts-and-their-related-metabolic-cross-talk-with-internal-homeostasis-a-systematic-review-of-ugt-isoforms-for-precision-medicine
#13
REVIEW
Na Yang, Runbin Sun, Xiaoying Liao, Jiye Aa, Guangji Wang
UDP-glucuronosyltransferases (UGTs) are the primary phase II enzymes catalyzing the conjugation of glucuronic acid to the xenobiotics with polar groups for facilitating their clearance. The UGTs belong to a superfamily that consists of diverse isoforms possessing distinct but overlapping metabolic activity. The abnormality or deficiency of UGTs in vivo is highly associated with some diseases, efficacy and toxicity of drugs, and precisely therapeutic personality. Despite the great effects and fruitful results achieved, to date, the expression and functions of individual UGTs have not been well clarified, the inconsistency of UGTs is often observed in human and experimental animals, and the complex regulation factors affecting UGTs have not been systematically summarized...
May 4, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28465217/antidepressants-induce-autophagy-dependent-nlrp3-inflammasome-inhibition-in-major-depressive-disorder
#14
Elísabet Alcocer-Gómez, Nieves Casas-Barquero, Matthew R Williams, Samuel L Romero-Guillena, Diego Cañadas-Lozano, Pedro Bullón, José Antonio Sánchez-Alcazar, José M Navarro-Pando, Mario D Cordero
Major Depressive Disorder (MDD, ICD-10: F-33) is a prevalent illness in which the pathogenic mechanism remains elusive. Recently an important role has been attributed to neuro-inflammation, and specifically the NLRP3-inflammasome complex, in the pathogenesis of MDD. This suggests a key role for immunomodulation as a key pathway in the treatment of this disorder. This study evaluates the involvement of nine common antidepressants in the NLRP3-inflammasome complex (fluoxetine, paroxetine, mianserin, mirtazapine, venlafaxine, desvenlafaxine, amitriptyline, imipramine and agomelatine), both in in vitro THP-1 cells stimulated by ATP, and in a stress-induced depressive animal or MDD patients...
May 2, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28473246/towards-therapeutic-drug-monitoring-of-everolimus-in-cancer-results-of-an-exploratory-study-of-exposure-effect-relationship
#15
Marine Deppenweiler, Sabrina Falkowski, Franck Saint-Marcoux, Caroline Monchaud, Nicolas Picard, Marie-Laure Laroche, Nicole Tubiana-Mathieu, Laurence Venat-Bouvet, Pierre Marquet, Jean-Baptiste Woillard
INTRODUCTION: Therapeutic drug monitoring (TDM) of everolimus is not performed in oncology and no trough level (C0) target has been yet defined. The aim of this study was to determine everolimus C0 target for toxicity and efficacy. MATERIALS AND METHODS: Clinical, biological and radiologic data from 54 patients were collected. Toxicity event was defined by termination, temporary interruption and/or dose reduction of everolimus while efficacy was defined as progression-free survival...
May 1, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28465216/ros1-protein-tyrosine-kinase-inhibitors-in-the-treatment-of-ros1-fusion-protein-driven-non-small-cell-lung-cancers
#16
REVIEW
Robert Roskoski
ROS1 protein-tyrosine kinase fusion proteins are expressed in 1-2% of non-small cell lung cancers. The ROS1 fusion partners include CD74, CCDC6, EZR, FIG, KDELR2, LRIG3, MSN, SDC4, SLC34A2, TMEM106B, TMP3, and TPD52L1. Physiological ROS1 is closely related to the ALK, LTK, and insulin receptor protein-tyrosine kinases. ROS1 is a so-called orphan receptor because the identity of its activating ligand, if any, is unknown. The receptor is expressed during development, but little is expressed in adults and its physiological function is unknown...
April 30, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28456683/patchouli-alcohol-ameliorates-dextran-sodium-sulfate-induced-experimental-colitis-and-suppresses-tryptophan-catabolism
#17
Chang Qu, Zhong-Wen Yuan, Xiu-Ting Yu, Yan-Feng Huang, Guang-Hua Yang, Jian-Nan Chen, Xiao-Ping Lai, Zi-Ren Su, Hui-Fang Zeng, Ying Xie, Xiao-Jun Zhang
Despite the increased morbidity of ulcerative colitis (UC) in recent years, available treatments remain unsatisfactory. Pogostemon cablin has been widely applied to treat a variety of gastrointestinal disorders in clinic for centuries, in which patchouli alcohol (PA, C15H26O) has been identified as the major active component. This study attempted to determine the bioactivity of PA on dextran sulfate sodium (DSS)-induced mice colitis and clarify the mechanism of action. Acute colitis was induced in mice by 3% DSS for 7 days...
April 27, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28455267/metabotropic-glutamate-receptor-5-mediates-the-suppressive-effect-of-6-ohda-induced-model-of-parkinson-s-disease-on-liver-cancer
#18
Shao-Song Xi, Xiao-Xu Bai, Li Gu, Li-Hui Bao, Hui-Min Yang, Wei An, Xiao-Min Wang, Hong Zhang
Numerous epidemiological studies suggested that there is a variable cancer risk in patients with Parkinson's disease (PD). However, the underlying mechanisms remain unclear. In the present study, the role of metabotropic glutamate receptor 5 (mGluR5) has been investigated in 6-hydroxydopamine (6-OHDA)-induced PD combined with liver cancer both in vitro and in vivo. We found that PD cellular model from 6-OHDA-lesioned MN9D cells suppressed the growth, migration, and invasion of Hepa1-6 cells via down-regulation of mGluR5-mediated ERK and Akt pathway...
April 26, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28455266/suppression-of-abcg2-mediated-mdr-in-vitro-and-in-vivo-by-a-novel-inhibitor-of-abcg2-drug-transport
#19
Atish Patel, Tian-Wen Li, Nagaraju Anreddy, De-Shen Wang, Kamlesh Sodani, Sanket Gadhia, Rishil Kathawala, Dong-Hua Yang, Changmei Cheng, Zhe-Sheng Chen
Cancer is a disease whose treatment is often limited due to the development of a phenomenon known as multidrug resistance (MDR). There is an immense demand for development of novel agents that can overcome the MDR in cancer. A group of transmembrane proteins called ATP-binding cassette transporters, present ubiquitously in the human body possesses a modular architecture, contributing immensely towards the development of MDR. An analysis of structural congeners among a group of compounds led to the discovery of CCTA-1523 that could selectively reverse ABCG2-mediated MDR in cancer cells in vitro and in vivo...
April 26, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28455265/age-and-sex-in-drug-development-and-testing-for-adults
#20
REVIEW
Cara Tannenbaum, Danielle Day
Individualization of drug therapy requires that the right drug be administered at the correct dose to patients who are likely to achieve the highest benefit and lowest risk. Female sex and age comprise two important risk factors for altered drug exposure and response. This review summarizes the current state of science for considering age and sex-related factors along the drug development pipeline, from cell culture and animal research through all phases of clinical trials in humans. A set of recommendations is provided to improve standards for integrating age and sex into the study design, analysis, and reporting of pre-clinical and clinical assessment of new molecular entities and biologics in adults...
April 26, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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