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https://www.readbyqxmd.com/read/28630289/green-mamba-peptide-targets-type-2-vasopressin-receptor-against-polycystic-kidney-disease
#1
Justyna Ciolek, Helen Reinfrank, Loïc Quinton, Say Viengchareun, Enrico A Stura, Laura Vera, Sabrina Sigismeau, Bernard Mouillac, Hélène Orcel, Steve Peigneur, Jan Tytgat, Laura Droctové, Fabrice Beau, Jerome Nevoux, Marc Lombès, Gilles Mourier, Edwin De Pauw, Denis Servent, Christiane Mendre, Ralph Witzgall, Nicolas Gilles
Polycystic kidney diseases (PKDs) are genetic disorders that can cause renal failure and death in children and adults. Lowering cAMP in cystic tissues through the inhibition of the type-2 vasopressin receptor (V2R) constitutes a validated strategy to reduce disease progression. We identified a peptide from green mamba venom that exhibits nanomolar affinity for the V2R without any activity on 155 other G-protein-coupled receptors or on 15 ionic channels. Mambaquaretin-1 is a full antagonist of the V2R activation pathways studied: cAMP production, beta-arrestin interaction, and MAP kinase activity...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28626017/amyloid-beta-peptide-is-needed-for-cgmp-induced-long-term-potentiation-and-memory
#2
Agostino Palmeri, Roberta Ricciarelli, Walter Gulisano, Daniela Rivera, Claudia Rebosio, Elisa Calcagno, Maria Rosaria Tropea, Silvia Conti, Utpal Das, Subhojit Roy, Maria A Pronzato, Ottavio Arancio, Ernesto Fedele, Daniela Puzzo
High levels of amyloid-beta peptide (Aβ) have been related to Alzheimer's disease pathogenesis. However, in the healthy brain, low physiologically relevant concentrations of Aβ are necessary for long-term potentiation (LTP) and memory. Because cGMP plays a key role in these processes, here we investigated whether the cyclic nucleotide cGMP influences Aβ levels and function during LTP and memory. We demonstrate that the increase of cGMP levels by the phosphodiesterase-5 inhibitors (PDE5-Is) sildenafil and vardenafil induces a parallel release of Aβ due to a change in the approximation of amyloid precursor protein (APP) and the β-site APP cleaving enzyme 1 (BACE1)...
June 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28625142/proteotoxic-stress-desensitizes-tgf-beta-signaling-through-receptor-downregulation-in-retinal-pigment-epithelial-cells
#3
X Tan, C Chen, Y Zhu, J Deng, X Qiu, S Huang, F Shang, B Cheng, Y Liu
BACKGROUND: Transforming growth factor (TGFβ)-induced epithelial-mesenchymal transition (EMT) and proteotoxic stress are two main contributors of intraocular fibrotic disorders, including proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). However, how these two factors communicate with each other is not well-characterized. OBJECTIVE: The aim was to investigate the regulatory role of proteotoxic stress on TGFβ signaling in retinal pigment epithelium...
June 19, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28572492/beta-1-versus-beta-2-adrenergic-control-of-coronary-blood-flow-during-isometric-handgrip-exercise-in-humans
#4
Stephan R Maman, Alvaro F Vargas, Tariq Ali Ahmad, Amanda J Miller, Zhaohui Gao, Urs A Leuenberger, David N Proctor, Matthew D Muller
During exercise, β-adrenergic receptors are activated throughout the body. In healthy humans, the net effect of β-adrenergic stimulation is an increase in coronary blood flow. However, the role of vascular β1 versus β2 receptors in coronary exercise hyperemia is not clear. In this study we simultaneously measured noninvasive indices of myocardial oxygen supply (i.e., blood velocity in the left anterior descending coronary artery; Doppler echocardiography) and demand (i.e., rate pressure product; RPP = heart rate x systolic blood pressure) and tested the hypothesis that β1 blockade with esmolol improves coronary exercise hyperemia compared to nonselective β-blockade with propranolol...
June 1, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28561945/beta-blocker-administration-during-emergency-department-evaluation-for-acute-coronary-syndrome-is-associated-with-lower-posttraumatic-stress-symptoms-1-month-later
#5
Laura Meli, Bernard P Chang, Daichi Shimbo, Brendan W Swan, Donald Edmondson, Jennifer A Sumner
We examined whether beta blocker administration in the emergency department (ED) during evaluation for suspected acute coronary syndrome (ACS) was associated with posttraumatic stress disorder (PTSD) symptoms 1-month later. Participants (N = 350) were enrolled in the Reactions to Acute Care and Hospitalization (REACH) study, an ongoing observational cohort study of ED predictors of medical and psychological outcomes after evaluation for suspected ACS. Beta blockade during evaluation in the ED was extracted from medical records, and PTSD symptoms in response to the experience of suspected ACS were assessed 1-month later via telephone...
May 31, 2017: Journal of Traumatic Stress
https://www.readbyqxmd.com/read/28560263/dopamine-d2-receptors-and-the-circadian-clock-reciprocally-mediate-antipsychotic-drug-induced-metabolic-disturbances
#6
Zachary Freyberg, Michael J McCarthy
Antipsychotic drugs are widely prescribed medications, used for numerous psychiatric illnesses. However, antipsychotic drugs cause serious metabolic side effects that can lead to substantial weight gain and increased risk for type 2 diabetes. While individual drugs differ, all antipsychotic drugs may cause these important side effects to varying degrees. Given that the single unifying property shared by these medications is blockade of dopamine D2 and D3 receptors, these receptors likely play a role in antipsychotic drug-induced metabolic side effects...
2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28551699/the-role-of-somatostatin-in-glp-1-induced-inhibition-of-glucagon-secretion-in-mice
#7
Anne Ørgaard, Jens J Holst
AIMS/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1) receptor agonists are currently used for the treatment of type 2 diabetes. Their main mechanism of action is enhancement of glucose-induced insulin secretion (from increased beta cell glucose sensitivity) and inhibition of glucagon secretion. The latter has been demonstrated to account for about half of their blood glucose-lowering activity. Whereas the effect of GLP-1 on insulin secretion is clearly dependent on ambient glucose concentrations and has been described in detail, the mechanism responsible for the inhibitory effect of GLP-1 on glucagon secretion is heavily debated...
May 27, 2017: Diabetologia
https://www.readbyqxmd.com/read/28541596/effects-of-ivabradine-and-beta-blocker-therapy-on-dobutamine-induced-ventricular-arrhythmias
#8
Kadir Uğur Mert, Gurbet Özge Mert, Bektas Morrad, Senan Tahmazov, Fezan Mutlu, Yüksel Cavusoglu
BACKGROUND: Indirect evidences suggest that the If blocker (ivabradine) may exert an antiarrhythmic effect in ventricular myocardium in heart failure patients by inhibiting spontaneous depolarizations but the clinical relevance of this mechanism is not known. Dobutamine (DOB) has been known to increase heart rate and the incidence of cardiac arrhythmias. In this study, we evaluated the effects of ivabradine on DOB-induced ventricular arrhythmias and compared it with that of β blocker therapy...
May 25, 2017: Kardiologia Polska
https://www.readbyqxmd.com/read/28536305/shaping-the-tumor-stroma-and-sparking-immune-activation-by-cd40-and-4-1bb-signaling-induced-by-an-armed-oncolytic-virus
#9
Emma Eriksson, Ioanna Milenova, Jessica Wenthe, Magnus Ståhle, Justyna Leja-Jarblad, Gustav Ullenhag, Anna Dimberg, Rafael Moreno, Ramon Alemany, Angelica Loskog
PURPOSE: Pancreatic cancer is a severe indication with short expected survival despite surgery and/or combination chemotherapeutics. Checkpoint blockade antibodies are approved for several cancer indications but pancreatic cancer has remained refractory. However, there are clinical data suggesting that stimulation of the CD40 pathway may be of interest for these patients. Oncolytic viruses armed with immunostimulatory genes represent an interesting approach. Herein we present LOAd703, a designed adenovirus armed with trimerized CD40L and 4-1BBL that activate the CD40 and 4-1BB pathways, respectively...
May 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28534174/the-il-1%C3%AE-phenomena-in-neuroinflammatory-diseases
#10
REVIEW
Andrew S Mendiola, Astrid E Cardona
It is becoming increasingly clear that neuroinflammation has a causal role in the pathogenesis of central nervous system (CNS)-related diseases, and therefore therapeutic strategies targeting the regulation or availability of inflammatory mediators can be used to prevent or mitigate pathology. Interestingly, the proinflammatory cytokine, interleukin-1 beta (IL-1β), has been implicated in perpetuating immune responses and contributing to disease severity in a variety of CNS diseases ranging from multiple sclerosis, neurodegenerative diseases, traumatic brain injury, and diabetic retinopathy...
May 22, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28521892/achieving-a-maximally-tolerated-%C3%AE-blocker-dose-in-heart-failure-patients-is-there-room%C3%A2-for%C3%A2-improvement
#11
REVIEW
Ankeet S Bhatt, Adam D DeVore, Tracy A DeWald, Karl Swedberg, Robert J Mentz
Heart failure (HF) is associated with significant morbidity and mortality. Although initially thought to be harmful in HF, beta-adrenergic blockers (β-blockers) have consistently been shown to reduce mortality and HF hospitalization in chronic HF with reduced ejection fraction. Proposed mechanisms include neurohormonal blockade and heart rate reduction. A new therapeutic agent now exists to target further heart rate lowering in patients who have been stable on a "maximally tolerated β-blocker dose," but this definition and how to achieve it are incompletely understood...
May 23, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28494868/interferon-receptor-signaling-pathways-regulating-pd-l1-and-pd-l2-expression
#12
Angel Garcia-Diaz, Daniel Sanghoon Shin, Blanca Homet Moreno, Justin Saco, Helena Escuin-Ordinas, Gabriel Abril Rodriguez, Jesse M Zaretsky, Lu Sun, Willy Hugo, Xiaoyan Wang, Giulia Parisi, Cristina Puig Saus, Davis Y Torrejon, Thomas G Graeber, Begonya Comin-Anduix, Siwen Hu-Lieskovan, Robert Damoiseaux, Roger S Lo, Antoni Ribas
PD-L1 and PD-L2 are ligands for the PD-1 immune inhibiting checkpoint that can be induced in tumors by interferon exposure, leading to immune evasion. This process is important for immunotherapy based on PD-1 blockade. We examined the specific molecules involved in interferon-induced signaling that regulates PD-L1 and PD-L2 expression in melanoma cells. These studies revealed that the interferon-gamma-JAK1/JAK2-STAT1/STAT2/STAT3-IRF1 axis primarily regulates PD-L1 expression, with IRF1 binding to its promoter...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28490464/perioperative-cox-2-and-beta-adrenergic-blockade-improves-metastatic-biomarkers-in-breast-cancer-patients-in-a-phase-ii-randomized-trial
#13
Lee Shaashua, Maytal Shabat-Simon, Rita Haldar, Pini Matzner, Oded Zmora, Moshe Shabtai, Eran Sharon, Tanir Allweis, Iris Barshack, Lucile Hayman, Jesusa M G Arevalo, Jeffrey Ma, Maya Horowitz, Steve W Cole, Shamgar Ben-Eliyahu
<br /> <p>Translational studies suggest that excess perioperative release of catecholamines and prostaglandins may facilitate metastasis and reduce disease-free survival. This trial tested the combined perioperative blockade of these pathways in breast cancer patients.</p> <br />Experimental Design: <br /> <p>In a randomized placebo-controlled biomarker trial, 38 early-stage breast cancer patients received 11 days of perioperative treatment with a beta-adrenergic antagonist (propranolol) and a cyclooxygenase-2 (COX-2) inhibitor (etodolac), beginning five days before surgery...
May 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28471068/stellate-ganglion-blockade-and-bilateral-cardiac-sympathetic-denervation-in-patients-with-life-threatening-ventricular-arrhythmias
#14
Ricardo Cardona-Guarache, Santosh K Padala, Luis Velazco-Davila, Anthony Cassano, Antonio Abbate, Kenneth A Ellenbogen, Jayanthi Koneru
Autonomic modulation is being increasingly employed as a strategy to treat ventricular arrhythmias refractory to beta-blockers, antiarrhythmic drugs and catheter-based ablation procedures. We report 6 patients with refractory ventricular tachycardia (VT) or ventricular fibrillation (VF) treated with stellate ganglion blockade (SGB) and/or bilateral cardiac sympathetic denervation (CSD). Our case series emphasizes the concept that the cardiac sympathetic nerves are important targets in the management of ventricular arrhythmias...
May 4, 2017: Journal of Cardiovascular Electrophysiology
https://www.readbyqxmd.com/read/28469578/beta-adrenergic-regulation-of-intrapulmonary-arteriovenous-anastomoses-in-intact-rat-and-isolated-rat-lungs
#15
Melissa L Bates, Joseph E Jacobson, Marlowe W Eldridge
Intrapulmonary arteriovenous anastomoses (IPAVA) allow large diameter particles of venous origin to bypass the pulmonary capillary bed and embolize the systemic arterial circulation. IPAVA have been routinely observed in healthy humans with exercise, hypoxia, and catecholamine infusion, but the mechanism by which they are recruited is not well-defined. We hypothesized that beta-adrenergic receptor stimulation recruits IPAVA and that receptor blockade would limit hypoxia-induced IPAVA recruitment. To test our hypothesis, we evaluated the transpulmonary passage of microspheres in intact rats and isolated rats lung infused with the beta-adrenergic receptor agonist isoproterenol...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28448588/allogeneic-pasc-transplantation-in-humanized-pigs-attenuates-cardiac-remodeling-post-myocardial-infarction
#16
Rafael Dariolli, Marcus V Naghetini, Euclydes F Marques, Celso K Takimura, Leonardo S Jensen, Bianca Kiers, Jeane M Tsutsui, Wilson Mathias, Pedro A Lemos Neto, Jose E Krieger
Cell therapy repair strategies using adult mesenchymal stromal cells have shown promising evidence to prevent cardiac deterioration in rodents even in the absence of robust differentiation of the cells into cardiomyocytes. We tested whether increasing doses of porcine adipose-tissue derived mesenchymal stem cells (pASCs) increase cardiac tissue perfusion in pigs post-myocardial infarction (MI) receiving angiotensin-converting-enzyme inhibitor (ACE inhibitors) and Beta-blockers similarly to patients. Female pigs were subjected to MI induction by sponge permanent occlusion of left circumflex coronary artery (LCx) generating approximately 10% of injured LV area with minimum hemodynamic impact...
2017: PloS One
https://www.readbyqxmd.com/read/28423042/transforming-growth-factor-%C3%AE-1-enhances-heme-oxygenase-1-expression-in-human-synovial-fibroblasts-by-inhibiting-microrna-519b-synthesis
#17
Shu-Jui Kuo, Wei-Hung Yang, Shan-Chi Liu, Chun-Hao Tsai, Horng-Chaung Hsu, Chih-Hsin Tang
BACKGROUND: Osteoarthritis (OA) is manifested by synovial inflammation and cartilage destruction that is directly linked to synovitis, joint swelling and pain. In the light of the role of synovium in the pathogenesis and the symptoms of OA, synovium-targeted therapy is a promising strategy to mitigate the symptoms and progression of OA. Transforming growth factor beta 1 (TGF-β1), a secreted homodimeric protein, possesses unique and potent anti-inflammatory and immune-regulatory properties in many cell types...
2017: PloS One
https://www.readbyqxmd.com/read/28414676/pheochromocytoma-of-the-organ-zuckerkandl
#18
C Lee, E Chang, J Gimenez, R McCarron
INTRODUCTION: Pheochromocytomas (PCCs);, or intra-adrenal paragangliomas (PGLs);, are neuroendocrine tumors arising within the adrenal medulla. Extra-adrenal paragangliomas may arise in the sympathetic or parasympathetic paraganglia and more rarely in other organs. One of the most common extra-adrenal sites is in the organ of Zuckerkandl, a collection of chromaffin cells near the origin of the inferior mesenteric artery or near the aortic bifurcation. The following is a case of a patient with resistant hypertension secondary to an extra-adrenal paraganglioma in the organ of Zuckerkandl...
March 2017: Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society
https://www.readbyqxmd.com/read/28410967/involvement-of-alpha-and-beta-adrenoceptors-in-the-automaticity-of-the-isolated-guinea-pig-pulmonary-vein-myocardium
#19
Masahiko Irie, Yayoi Tsuneoka, Mariko Shimobayashi, Nao Hasegawa, Yusuke Tanaka, Soh Mochizuki, Sho Ichige, Shogo Hamaguchi, Iyuki Namekata, Hikaru Tanaka
We examined the involvement of adrenoceptors in the automaticity of the pulmonary vein myocardium, which probably plays a crucial role in the generation of atrial fibrillation. The automatic activity of the myocardium in guinea pig pulmonary vein tissue preparations were monitored by contractile force or membrane potential measurement. In quiescent preparations, application of noradrenaline induced an automatic activity. The firing frequency was reduced by prazosin or atenolol. Methoxamine induced an automatic activity of low frequency, which was accelerated by further application of isoproterenol...
April 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28396860/aortic-valve-replacement-for-moderate-aortic-stenosis-with-severe-calcification-and-left-ventricualr-dysfunction-a-case-report-and-review-of-the-literature
#20
Nikhil Narang, Roberto M Lang, Vladimir M Liarski, Valluvan Jeevanandam, Marion A Hofmann Bowman
A 55-year-old man with a history of erosive, seropositive rheumatoid arthritis (RA), and interstitial lung disease presented with shortness of breath. Echocardiography showed new-onset severe left ventricular (LV) dysfunction with an ejection fraction (EF) of 15% and moderately increased mean aortic valve gradient of 20 mmHg in a trileaflet aortic valve with severe sclero-calcific degeneration. Coronary angiography revealed no significant obstructive coronary disease. Invasive hemodynamic studies and dobutamine stress echocardiography were consistent with moderate aortic stenosis...
2017: Frontiers in Cardiovascular Medicine
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