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https://www.readbyqxmd.com/read/29774054/beta-adrenoceptor-blockade-ameliorates-impaired-glucose-tolerance-and-alterations-of-the-cerebral-ceramide-metabolism-in-an-experimental-model-of-ischemic-stroke
#1
Sebastian Luger, Annette Schwebler, Rajkumar Vutukuri, Nerea Ferreiros Bouzas, Sandra Labocha, Yannick Schreiber, Robert Brunkhorst, Helmuth Steinmetz, Josef Pfeilschifter, Waltraud Pfeilschifter
Background: Sphingolipids are versatile signaling molecules derived from membrane lipids of eukaryotic cells. Ceramides regulate cellular processes such as proliferation, differentiation and apoptosis and are involved in cellular stress responses. Experimental evidence suggests a pivotal role of sphingolipids in the pathogenesis of cardiovascular diseases, including ischemic stroke. A neuroprotective effect has been shown for beta-adrenergic antagonists in rodent stroke models and supported by observational clinical data...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29773827/cardiac-pacemaker-channel-hcn4-inhibition-and-atrial-arrhythmogenesis-after-releasing-cardiac-sympathetic-activation
#2
Kristine Chobanyan-Jürgens, Karsten Heusser, David Duncker, Christian Veltmann, Marcus May, Heidrun Mehling, Friedrich C Luft, Christoph Schröder, Jens Jordan, Jens Tank
Clinical trials and studies with ivabradine implicate cardiac pacemaker channels (HCN4) in the pathogenesis of atrial arrhythmias. Because acute changes in cardiac autonomic tone predispose to atrial arrhythmias, we studied humans in whom profound cardiac sympathetic activation was rapidly relieved to test influences of HCN4 inhibition with ivabradine on atrial arrhythmias. We tested 19 healthy participants with ivabradine, metoprolol, or placebo in a double blind, randomized, cross-over fashion on top of selective norepinephrine reuptake inhibition with reboxetine...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29755479/lysophosphatidylcholine-promotes-phagosome-maturation-and-regulates-inflammatory-mediator-production-through-the-protein-kinase-a-phosphatidylinositol-3-kinase-p38-mitogen-activated-protein-kinase-signaling-pathway-during-mycobacterium-tuberculosis-infection
#3
Hyo-Ji Lee, Hyun-Jeong Ko, Dong-Kun Song, Yu-Jin Jung
Tuberculosis is caused by the infectious agent Mycobacterium tuberculosis (Mtb). Mtb has various survival strategies, including blockade of phagosome maturation and inhibition of antigen presentation. Lysophosphatidylcholine (LPC) is a major phospholipid component of oxidized low-density lipoprotein and is involved in various cellular responses, such as activation of second messengers and bactericidal activity in neutrophils. In this study, macrophages were infected with a low infectious dose of Mtb and treated with LPC to investigate the bactericidal activity of LPC against Mtb...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29753717/trim38-regulates-nf-%C3%AE%C2%BAb-activation-through-tab2-degradation-in-osteoclast-and-osteoblast-differentiation
#4
Kabsun Kim, Jung Ha Kim, Inyoung Kim, Semun Seong, Nacksung Kim
The tripartite motif protein 38 (TRIM38), a member of the TRIM family, is involved in various cellular processes such as cell proliferation, differentiation, apoptosis, and antiviral defense. However, the role of TRIM38 in osteoclast and osteoblast differentiation is not yet known. In this study, we report the involvement of TRIM38 in osteoclast and osteoblast differentiation. Overexpression of TRIM38, in osteoclast precursor cells, attenuated receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast formation, RANKL-triggered NF-κB activation, and expression of osteoclast marker genes, such as NFATc1, osteoclast-associated receptor (OSCAR), and tartrate-resistant acid phosphatase (TRAP); and down-regulation of TRIM38 expression showed the opposite effects...
May 10, 2018: Bone
https://www.readbyqxmd.com/read/29743821/blockade-of-itga2-induces-apoptosis-and-inhibits-cell-migration-in-gastric-cancer
#5
Yu-Chang Chuang, Hsin-Yi Wu, Yu-Ling Lin, Shey-Cherng Tzou, Cheng-Hsun Chuang, Ting-Yan Jian, Pin-Rong Chen, Yuan-Ching Chang, Chi-Hsin Lin, Tse-Hung Huang, Chao-Ching Wang, Yi-Lin Chan, Kuang-Wen Liao
Background: Gastric cancer is currently the fourth leading cause of cancer-related death worldwide. Gastric cancer is often diagnosed at advanced stages and the outcome of the treatment is often poor. Therefore, identifying new therapeutic targets for this cancer is urgently needed. Integrin alpha 2 (ITGA2) subunit and the beta 1 subunit form a heterodimer for a transmembrane receptor for extracellular matrix, is an important molecule involved in tumor cell proliferation, survival and migration...
2018: Biological Procedures Online
https://www.readbyqxmd.com/read/29739794/race-and-beta-blocker-survival-benefit-in-patients-with-heart-failure-an-investigation-of-self-reported-race-and-proportion-of-african-genetic-ancestry
#6
Jasmine A Luzum, Edward Peterson, Jia Li, Ruicong She, Hongsheng Gui, Bin Liu, John A Spertus, Yigal M Pinto, L Keoki Williams, Hani N Sabbah, David E Lanfear
BACKGROUND: It remains unclear whether beta-blockade is similarly effective in black patients with heart failure and reduced ejection fraction as in white patients, but self-reported race is a complex social construct with both biological and environmental components. The objective of this study was to compare the reduction in mortality associated with beta-blocker exposure in heart failure and reduced ejection fraction patients by both self-reported race and by proportion African genetic ancestry...
May 8, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29728578/propranolol-sensitizes-prostate-cancer-cells-to-glucose-metabolism-inhibition-and-prevents-cancer-progression
#7
Laura Brohée, Olivier Peulen, Betty Nusgens, Vincent Castronovo, Marc Thiry, Alain C Colige, Christophe F Deroanne
Propranolol, a widely used non-selective beta-adrenergic receptor blocker, was recently shown to display anticancer properties. Its potential to synergize with certain drugs has been also outlined. However, it is necessary to take into account all the properties of propranolol to select a drug that could be efficiently combined with. Propranolol was reported to block the late phase of autophagy. Hence, we hypothesized that in condition enhancing autophagy flux, cancer cells should be especially sensitive to propranolol...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29723576/beta-and-gamma-oscillations-in-prefrontal-cortex-during-nmda-hypofunction-an-in-vitro-model-of-schizophrenia-features
#8
Beatriz Rebollo, Maria Perez-Zabalza, Marcel Ruiz-Mejias, Lorena Perez-Mendez, Maria V Sanchez-Vives
NMDA receptor (NMDAr) hypofunction has been widely used as a schizophrenia model. Decreased activation of NMDAr is associated with a disrupted excitation/inhibition balance in the prefrontal cortex and with alterations in gamma synchronization. Our aim was to investigate whether this phenomenon could be reproduced in the spontaneous oscillatory activity generated by the local prefrontal network in vitro and, if so, to explore the effects of antipsychotics on the resulting activity. Extracellular recordings were obtained from prefrontal cortex slices bathed in in vivo-like ACSF solution...
April 30, 2018: Neuroscience
https://www.readbyqxmd.com/read/29709367/inhibition-of-necroptosis-attenuates-lung-injury-and-improves-survival-in-neonatal-sepsis
#9
Alexandra C Bolognese, Weng-Lang Yang, Laura W Hansen, Naomi-Liza Denning, Jeffrey M Nicastro, Gene F Coppa, Ping Wang
BACKGROUND: Neonatal sepsis represents a unique therapeutic challenge owing to an immature immune system. Necroptosis is a form of programmed cell death that has been identified as an important mechanism of inflammation-induced cell death. Receptor-interacting protein kinase 1 plays a key role in mediating this process. We hypothesized that pharmacologic blockade of receptor-interacting protein kinase 1 activity would be protective in neonatal sepsis. METHODS: Sepsis was induced in C57BL/6 mouse pups (5-7 days old) by intraperitoneal injection of adult cecal slurry...
April 27, 2018: Surgery
https://www.readbyqxmd.com/read/29705815/pancreatic-%C3%AE-cells-overexpressing-hiapp-impaired-mitophagy-and-unbalanced-mitochondrial-dynamics
#10
Miriam García Hernández, Ana García Aguilar, Jesús Burillo, Raquel Gómez Oca, Maria Antonietta Manca, Ana Novials, Gema Alcarraz-Vizan, Carlos Guillén, Manuel Benito
Human islet amyloid polypeptide (hIAPP), or amylin, has the tendency to aggregate into insoluble amyloid fibrils, a typical feature of islets from type 2 diabetes individuals. Thus, we investigated comparatively the impact of hIAPP on key pathways involved in pancreatic beta survival. INS1E-hIAPP cells present a hyperactivation of MTORC1 and an inhibition of autophagy signaling, those cells showing an increase in cell size. Resveratrol, a MTORC1 inhibitor, can reverse TSC2 degradation that occurs in INS1E-hIAPP cells and diminished MTORC1 hyperactivation with concomitant autophagy stimulation...
April 29, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29687317/the-effects-of-heart-rate-control-in-chronic-heart-failure-with-reduced-ejection-fraction
#11
REVIEW
Dario Grande, Massimo Iacoviello, Nadia Aspromonte
Elevated heart rate has been associated with worse prognosis both in the general population and in patients with heart failure. Heart rate is finely modulated by neurohormonal signals and it reflects the balance between the sympathetic and the parasympathetic limbs of the autonomic nervous system. For this reason, elevated heart rate in heart failure has been considered an epiphenomenon of the sympathetic hyperactivation during heart failure. However, experimental and clinical evidence suggests that high heart rate could have a direct pathogenetic role...
April 23, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29675897/the-penumbral-role-of-beta-blockade-on-heart-rate-recovery-in-heart-failure
#12
Alan Pan
We would like to thank Bharadwaj et al. for their 2017 publication which provides robust evidence that subacute pyridostigmine administration heightens heart rate recovery (HRR) by augmenting cholinergic stimulus to the heart, thereby increasing parasympathetic tonus in heart failure (HF).1 Findings on HRR in the human population, which were published by another group in 20162 and correlate diminished HRR with HF mortality, belie what we truly know concerning the nebulous role that parasympathetic activation plays relative to standard therapy in HF...
April 19, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29665297/esmolol-acutely-alters-oxygen-supply-demand-balance-in-exercising-muscles-of-healthy-humans
#13
David N Proctor, J Carter Luck, Stephan R Maman, Urs A Leuenberger, Matthew D Muller
Beta-adrenoreceptor antagonists (β blockers) reduce systemic O2 delivery and blood pressure (BP) during exercise, but the subsequent effects on O2 extraction within the active limb muscles are unknown. In this study, we examined the effects of the fast-acting, β1 selective blocker esmolol on systemic hemodynamics and leg muscle O2 saturation (near infrared spectroscopy, NIRS) during submaximal leg ergometry. Our main hypothesis was that esmolol would augment exercise-induced reductions in leg muscle O2 saturation...
April 2018: Physiological Reports
https://www.readbyqxmd.com/read/29648813/small-molecule-neuropilin-1-antagonists-combine-anti-angiogenic-and-anti-tumour-activity-with-immune-modulation-through-reduction-of-transforming-growth-factor-beta-tgf%C3%AE-production-in-regulatory-t-cells
#14
Jonathan Powell, Filipa Mota, David Steadman, Christelle Soudy, Jeremy T Miyauchi, Stuart Crosby, Ashley Jarvis, Tifelle Reisinge, Natalie Winfield, Graham Evans, Aled Finniear, Tamas Yelland, Yi-Tai Chou, A W Edith Chan, Andrew O'Leary, Lili Cheng, Dan Liu, Ntina Fotinou, Carla Milagre, John F Martin, Haiyan Jia, Paul Frankel, Snezana Djordjevic, Stella E Tsirka, Ian C Zachary, David L Selwood
We report the design, synthesis and comprehensive studybiological evaluation of a range ofsome potent small-molecule neuropilin-1 (NRP1) antagonists. NRP1 is implicated in the immune response to tumours, particularly in Treg cell fragility, required for PD1 checkpoint blockade. The design of these compounds was based on a previously identified compound EG00229, EG00229 which was used a starting point for optimisation. Through targeting of specific amino-acid residues additional H-bonding interactions were introduced, which led to increases in binding affinity and potency...
April 12, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29628277/effect-of-beta-adrenergic-blockade-on-weight-changes-in-patients-with-chronic-heart-failure
#15
Shirley Sze, Pierpaolo Pellicori, Syed Kamzi, Alexandru Anton, Andrew L Clark
BACKGROUND: Weight loss is common in patients with chronic heart failure (CHF) and is associated with adverse outcome. Activation of the sympathetic nervous system has been implicated in weight loss, wasting and cachexia. However, the effect of sympathetic antagonism on weight change in patients with CHF is not well defined. METHODS: We evaluated changes in body weight, the incidence of cachexia (weight loss >6%) and significant weight gain (>5%) in unselected patients with CHF due to left ventricular systolic dysfunction (LVSD) (LV ejection fraction (LVEF) <40%) and studied the effect of beta-blockade on weight change...
March 22, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29608495/medical-management-of-rheumatic-heart-disease-a-systematic-review-of-the-evidence
#16
E Anne Russell, Warren F Walsh, Ben Costello, Alex Ja McLellan, Alex Brown, Christopher M Reid, Lavinia Tran, Graeme P Maguire
Rheumatic heart disease (RHD) is an important cause of heart disease globally. Its management can encompass medical and procedural (catheter and surgical) interventions. Literature pertaining to the medical management of RHD from PubMed 1990-2016 and via selected article reference lists was reviewed. Areas included symptom management, left ventricular (LV) dysfunction, rate control in mitral stenosis (MS), atrial fibrillation (AF), anticoagulation, infective endocarditis prophylaxis and management in pregnancy...
March 30, 2018: Cardiology in Review
https://www.readbyqxmd.com/read/29589072/the-resident-macrophages-in-murine-pancreatic-islets-are-constantly-probing-their-local-environment-capturing-beta-cell-granules-and-blood-particles
#17
Bernd H Zinselmeyer, Anthony N Vomund, Brian T Saunders, Michael W Johnson, Javier A Carrero, Emil R Unanue
AIMS/HYPOTHESIS: We studied here the interactions between the resident macrophages of pancreatic islets with beta cells and the blood vasculature. We also examined the immunological consequences of such interactions. METHODS: Islets were isolated from C57BL/6 mice expressing CX3C motif chemokine receptor 1-green fluorescent protein (CX3CR-GFP) and examined live by two-photon microscopy. Islets were also examined by electron microscopy to study the relationship of the intra-islet macrophages with the beta cells...
March 27, 2018: Diabetologia
https://www.readbyqxmd.com/read/29588232/the-effect-of-beta-adrenergic-blockade-on-inflammatory-and-cardiovascular-responses-to-acute-mental-stress
#18
Andrew Steptoe, Amy Ronaldson, Karen Kostich, Antonio I Lazzarino, Livia Urbanova, Livia A Carvalho
Acute mental stress elicits increases in plasma cytokine concentrations in humans, but the underlying mechanisms remain poorly understood. We assessed the impact of beta-adrenergic blockade on plasma interleukin 6 (IL-6) and IL-1 receptor antagonist (IL-1Ra) responses in a parallel group, double-blind randomised placebo-controlled trial involving 64 healthy young adult volunteers. Participants were administered 80 mg slow-release propranolol or placebo daily for 7 days before the stress testing session in which responses to 3 behavioural challenges (public speaking, mirror tracing, mental arithmetic) were evaluated...
March 26, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29584915/interleukin-1-blockade-in-cardiovascular-diseases-a-clinical-update
#19
Leo F Buckley, Antonio Abbate
Interleukin-1 (IL-1) is the prototypical pro-inflammatory cytokine. IL-1 was implicated as a cardiodepressant factor in septic shock, and subsequent pre-clinical and clinical research has defined important roles for IL-1 in atherosclerosis, acute myocardial infarction (AMI), and heart failure (HF). IL-1 promotes the formation of the atherosclerotic plaque and facilitates its progression and complication. In a large phase III clinical trial of stable patients with prior AMI, blocking IL-1 activity using a monoclonal antibody prevented recurrent atherothrombotic cardiovascular events...
March 23, 2018: European Heart Journal
https://www.readbyqxmd.com/read/29580170/comparison-of-therapeutic-triiodothyronine-versus-metoprolol-in-treatment-of-myocardial-infarction-in-rats
#20
Kuo Zhang, Yi-Da Tang, Youhua Zhang, Kaie Ojamaa, Ying Li, Amandeep Singh Saini, Maria Alicia Carrillo-Sepulveda, Viswanathan Rajagopalan, A Martin Gerdes
BACKGROUND: Beta blockers are standard therapy for myocardial infarction (MI). Preclinical studies have shown efficacy and safety of thyroid hormone (TH) treatment of cardiovascular disorders. Since THs interact with the sympathoadrenergic system, we aimed to compare triiodothyronine (T3) and metoprolol (Met) treatment of rats with MI on pathophysiology and TH-adrenergic signaling. METHODS: Female Sprague-Dawley rats aged 12 weeks underwent left anterior descending coronary artery ligation (MI) or sham surgeries...
March 26, 2018: Thyroid: Official Journal of the American Thyroid Association
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