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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
#1
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
#2
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
#3
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...
March 29, 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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28337414/pheochromocytoma-with-negative-metanephrines-a-rarity-and-the-significance-of-dopamine-secreting-tumors
#14
Michael Bozin, Alastair Lamb, Lydia Johns Putra
We describe a case of a 25-year-old female with a dopamine secreting PPGL diagnosed retrospectively with biochemical analysis. This finding resulted in change in approach to investigation and management, given their important clinical implications. There are important differences in management of dopamine secreting PPGL compared to classical noradrenaline and adrenaline-secreting PPGL. This includes the risk of peri-operative cardiovascular collapse peri-operatively with alpha/beta blockade, risk of malignancy/recurrence, and associated genetic abnormalities...
May 2017: Urology Case Reports
https://www.readbyqxmd.com/read/28323959/insulin-and-glucagon-partners-for-life
#15
Jens Juul Holst, William Holland, Jesper Gromada, Young Lee, Roger H Unger, Hai Yan, Kyle W Sloop, Timothy J Kieffer, Nicolas Damond, Pedro L Herrera
In August 2016, several leaders in glucagon biology gathered for the European Association for the Study of Diabetes Hagedorn Workshop in Oxford, England. A key point of discussion focused on the need for basal insulin to allow for the therapeutic benefit of glucagon blockade in the treatment of diabetes. Among the most enlightening experimental results presented were findings from studies in which glucagon receptor-deficient mice were administered streptozotocin to destroy pancreatic β cells or had undergone diphtheria toxin-induced β cell ablation...
April 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28292194/clinical-utility-of-sympathetic-blockade-in-cardiovascular-disease-management
#16
REVIEW
Chan Soon Park, Hae-Young Lee
A dysregulated sympathetic nervous system is a major factor in the development and progression of cardiovascular disease; thus, understanding the mechanism and function of the sympathetic nervous system and appropriately regulating sympathetic activity to treat various cardiovascular diseases are crucial. Areas covered: This review focused on previous studies in managing hypertension, atrial fibrillation, coronary artery disease, heart failure, and perioperative management with sympathetic blockade. We reviewed both pharmacological and non-pharmacological management...
April 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/28285987/tgf%C3%AE-incurred-epigenetic-aberrations-of-mirna-and-dna-methyltransferase-suppress-klotho-and-potentiate-renal-fibrosis
#17
Shasha Yin, Qin Zhang, Jun Yang, Wenjun Lin, Yanning Li, Fang Chen, Wangsen Cao
Renal fibrosis is a common pathological feature of chronic kidney diseases (CKD) and its development and progression are significantly affected by epigenetic modifications such as aberrant miRNA and DNA methylation. Klotho is an anti-aging and anti-fibrotic protein and its early decline after renal injury is reportedly associated with aberrant DNA methylation. However, the key upstream pathological mediators and the molecular cascade leading to epigenetic Klotho suppression are not appreciably established. Here we investigate the epigenetic mechanism of Klotho deficiency and its functional relevance in renal fibrogenesis...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28280600/structural-basis-of-a-novel-pd-l1-nanobody-for-immune-checkpoint-blockade
#18
Fei Zhang, Hudie Wei, Xiaoxiao Wang, Yu Bai, Pilin Wang, Jiawei Wu, Xiaoyong Jiang, Yugang Wang, Haiyan Cai, Ting Xu, Aiwu Zhou
The use of antibodies to target immune checkpoints, particularly PD-1/PD-L1, has made a profound impact in the field of cancer immunotherapy. Here, we identified KN035, an anti-PD-L1 nanobody that can strongly induce T-cell responses and inhibit tumor growth. The crystal structures of KN035 complexed with PD-L1 and free PD-L1, solved here at 1.7 and 2.7 Å resolution, respectively, show that KN035 competes with PD-1 (programmed death protein 1) for the same flat surface on PD-L1, mainly through a single surface loop of 21 amino acids...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28279368/imaging-guided-cardioprotective-treatment-in-a-community-elderly-population-of-stage-b-heart-failure
#19
Hong Yang, Kazuaki Negishi, Ying Wang, Mark Nolan, Thomas H Marwick
OBJECTIVES: The purpose of the study was to evaluate the benefit of care guided by the detection of stage B heart failure (SBHF) using advanced echocardiography for the reduction of new HF in the community. BACKGROUND: The detection of nonischemic SBHF has been facilitated by advanced echocardiographic imaging modalities. However, improved outcomes have not been proven as they are predicated on benefit of treatment. METHODS: Between September 13, 2013 and November 6, 2015, 618 asymptomatic community-based patients with HF risks (age 71 ± 5 years) were randomized to care guided by advanced echocardiography (myocardial deformation and detailed diastolic function) versus usual care...
March 2017: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28265730/does-beta-blockade-reduce-the-risk-of-depression-in-patients-with-isolated-severe-extracranial-injuries
#20
Rebecka Ahl, Galinos Barmparas, Louis Riddez, Eric J Ley, Göran Wallin, Olle Ljungqvist, Shahin Mohseni
BACKGROUND: Approximately half of trauma patients develop post-traumatic depression. It is suggested that beta-blockade impairs trauma memory recollection, reducing depressive symptoms. This study investigates the effect of early beta-blockade on depression following severe traumatic injuries in patients without significant brain injury. METHODS: Patients were identified by retrospectively reviewing the trauma registry at an urban university hospital between 2007 and 2011...
March 6, 2017: World Journal of Surgery
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