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https://www.readbyqxmd.com/read/28534174/the-il-1%C3%AE-phenomena-in-neuroinflammatory-diseases
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28392767/early-onset-network-hyperexcitability-in-presymptomatic-alzheimer-s-disease-transgenic-mice-is-suppressed-by-passive-immunization-with-anti-human-app-a%C3%AE-antibody-and-by-mglur5-blockade
#12
Syed F Kazim, Shih-Chieh Chuang, Wangfa Zhao, Robert K S Wong, Riccardo Bianchi, Khalid Iqbal
Cortical and hippocampal network hyperexcitability appears to be an early event in Alzheimer's disease (AD) pathogenesis, and may contribute to memory impairment. It remains unclear if network hyperexcitability precedes memory impairment in mouse models of AD and what are the underlying cellular mechanisms. We thus evaluated seizure susceptibility and hippocampal network hyperexcitability at ~3 weeks of age [prior to amyloid beta (Aβ) plaque deposition, neurofibrillary pathology, and cognitive impairment] in a triple transgenic mouse model of familial AD (3xTg-AD mouse) that harbors mutated human Aβ precursor protein (APP), tau and presenilin 1 (PS1) genes...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28389717/sex-difference-in-expression-and-function-of-beta-adrenoceptors-in-macrovessels-role-of-the-endothelium
#13
Suzan Al-Gburi, Andreas Deussen, Birgit Zatschler, Silvio Weber, Stephan Künzel, Ali El-Armouche, Kristina Lorenz, Maria Cybularz, Henning Morawietz, Irakli Kopaliani
Estrogen modulates adrenergic reactivity of macrovessels, resulting in weaker α-adrenergic vasoconstriction in females than males. However, the mechanisms governing this important sex-specific difference are not well understood. We hypothesized that vessels of females express more dilatory β-adrenoceptors, which counteract constrictive effects of α-adrenoceptors. This hypothesis was tested using aortas of normotensive (WKY) and hypertensive rats (SHR), along with human mammary artery. Selective blockade of β1 (CGP20712) or β3 (SR59230A), but not β2 (ICI118,551) adrenoceptors, greatly increased α-adrenergic constriction (norepinephrine) of aorta in female SHRs, but not in male SHRs at 12 weeks of age...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28387384/nebivolol-valsartan-fixed-dose-combination-for-treatment-of-hypertension
#14
D M Paton
Clinical trials demonstrated that a fixed-dose combination (FDC) of the beta-blocker nebivolol (5 mg) and the angiotensin II antagonist valsartan (80 mg) produced a significant reduction of both diastolic and systolic blood pressure in patients with hypertension. Both nebivolol and valsartan contributed to this effect, partial additivity of 86.6% and 82.2% being observed for diastolic and systolic blood pressure, respectively. These values are very similar to the additivity ratios of other recently approved FDCs for hypertension...
January 2017: Drugs of Today
https://www.readbyqxmd.com/read/28374576/docking-based-design-and-synthesis-of-galantamine-ndash-camphane-hybrids-as-inhibitors-of-acetylcholinesterase
#15
Georgi Stavrakov, Irena Philipova, Dimitrina Zheleva-Dimitrova, Iva Valkova, Evdokiya Salamanova, Spiro Konstantinov, Irini Doytchinova
Galantamine (GAL) as an acetylcholinesterase inhibitor (AChEI) is among the main drugs approved for the treatment of Alzheimer's disease. It fits perfectly into acetylcholinesterase (AChE) binding gorge but it is too short to fill it. The amyloid beta (Aβ) peptide binds in the peripheral anionic site (PAS) at the entrance of the binding gorge of AChE and initiates the formation of amyloid plaques. The blockade of PAS prevents from AChE-induced Aβ aggregation. In the present study, we describe the design of a series of galantamine-camphane hybrids as AChEIs...
April 4, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28366317/morbidity-and-mortality-in-elective-total-hip-arthroplasty-following-surgical-care-improvement-project-guidelines
#16
Thomas B Bemenderfer, Nigel L Rozario, Charity G Moore, Madhav A Karunakar
BACKGROUND: Following evidence questioning the safety and efficacy of perioperative beta-blocker therapy in noncardiac surgery, the Surgical Care Improvement Project (SCIP) guidelines were retired in 2015. However, perioperative myocardial infarctions and cardiac complications remain leading causes of mortality following noncardiac surgery. The impact of the SCIP guidelines on reducing cardiac complications in patients undergoing elective total hip arthroplasty (THA) has not been evaluated...
March 9, 2017: Journal of Arthroplasty
https://www.readbyqxmd.com/read/28365181/sudden-death-in-ischemic-heart-disease-2017
#17
Alfred E Buxton
At this time, we find ourselves with an abundance of guidelines for management of patients with manifest ventricular tachyarrhythmias, or at risk for such arrhythmias, in patients with coronary heart disease (CHD). The guidelines are focused primarily on the "appropriate use" of the implantable cardioverter/defibrillator (ICD). Unfortunately, the bulk of the guidelines have very little basis in the underlying pathophysiology responsible for sudden cardiac death (SCD) in patients with CHD. Rather, they are based primarily on the results of randomized clinical trials that merely sought to take broad populations at elevated total mortality risk and determining whether the ICD can reduce overall mortality...
March 10, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28364364/possible-reversal-of-ptsd-related-dna-methylation-by-sympathetic-blockade
#18
REVIEW
Eugene G Lipov, Kenneth Candido, Elspeth C Ritchie
Studies have shown that brain-derived neurotrophic factor (BDNF) level increase is associated with post-traumatic stress disorder (PTSD) risk. BDNF may be a "missing-link" that mediates the interaction between genetics, environment, and the sympathetic system. Trauma has been shown to induce DNA methylation that in turn can increase BDNF concentration due to increased gene expression. Therapies that focus on the reduction of beta-NGF (BNGF) levels may impact PTSD symptoms. The focus of this paper is to discuss possible effect of stellate ganglion block (SGB) on epigenetic changes noted with PTSD mediated by BDNF and NGF...
March 31, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28359774/trpv4-regulates-insulin-mrna-expression-and-ins-1e-cell-death-via-erk1-2-and-no-dependent-mechanisms
#19
M Billert, M Skrzypski, M Sassek, D Szczepankiewicz, T Wojciechowicz, S Mergler, M Z Strowski, K W Nowak
TRPV4 is a Ca(2+)-permeable, nonselective cation channel. Recently, TRPV4 was implicated in controlling peripheral insulin sensitivity, insulin secretion and apoptosis of pancreatic beta cells. Here, we characterize the role and potential mechanisms of TRPV4 in regulating insulin mRNA expression and cell death in insulin producing INS-1E cells and rat pancreatic islets. TRPV4 protein production was downregulated by siRNA. Intracellular calcium level was measured using Fluo-3 AM. Gene expression was studied by real-time PCR...
March 27, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28339909/il-17-and-cd40-ligand-synergistically-stimulate-the-chronicity-of-diabetic-nephropathy
#20
Huey-Liang Kuo, Chiu-Ching Huang, Tze-Yi Lin, Ching-Yuang Lin
Background.: Early stages of diabetic nephropathy (DN) are characterized by an influx of inflammatory cells. Interactions between infiltrating T cells and podocytes may play an important role in the ongoing inflammatory response and remodelling. The aim of this study was to explore the role of IL-17 and CD40 ligand (CD40L) in DN. Methods.: The study design involved a case series. Kidney biopsy samples of 69 patients with type 2 diabetes were assessed for the presence of CD4 +  IL-17 +  T cells...
March 1, 2017: Nephrology, Dialysis, Transplantation
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