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https://www.readbyqxmd.com/read/28080974/how-the-heart-speaks-to-the-brain-neural-activity-during-cardiorespiratory-interoceptive-stimulation
#1
Mahlega S Hassanpour, Lirong Yan, Danny J J Wang, Rachel C Lapidus, Armen C Arevian, W Kyle Simmons, Jamie D Feusner, Sahib S Khalsa
Prominent theories emphasize key roles for the insular cortex in the central representation of interoceptive sensations, but how this brain region responds dynamically to changes in interoceptive state remains incompletely understood. Here, we systematically modulated cardiorespiratory sensations in humans using bolus infusions of isoproterenol, a rapidly acting peripheral beta-adrenergic agonist similar to adrenaline. To identify central neural processes underlying these parametrically modulated interoceptive states, we used pharmacological functional magnetic resonance imaging (phMRI) to simultaneously measure blood-oxygenation-level dependent (BOLD) and arterial spin labelling (ASL) signals in healthy participants...
November 19, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28058556/surgical-treatment-of-malignant-pheochromocytoma-and-paraganglioma-retrospective-case-series
#2
Veljko Strajina, Benzon M Dy, David R Farley, Melanie L Richards, Travis J McKenzie, Keith C Bible, Florencia G Que, David M Nagorney, William F Young, Geoffrey B Thompson
INTRODUCTION: Pheochromocytoma and paraganglioma (PPGL) are rare neoplasms; about 10% are malignant. Literature regarding possible benefit from resection is extremely limited. METHODS: A 20 year review of all patients undergoing surgery for malignant PPGL at the Mayo Clinic Rochester Campus between 1994 and June 2014 was performed. RESULTS: We identified 34 patients undergoing surgery for malignant PPGL. Median follow up was 6 and 5 years survival was 90% (median 11 years)...
January 5, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28035527/new-and-emerging-therapies-and-targets-beta-3-agonists
#3
Lauriane Y M Michel, Jean-Luc Balligand
While crucial for the acute physiologic response to stress, the adrenergic system may become maladaptive upon prolonged stimulation in the course of development of heart failure. This has been the basis for the development of beta-blocking therapies, targeting mainly beta1-2 adrenoreceptors (B1-2AR). The third isotype, B3AR, was more recently identified in cardiac myocytes and endothelial cells from human (and many other animal species), where its distinctive coupling to nitric oxide and antioxidant pathways suggested potential protective properties that were unexploited so far...
December 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28031536/use-of-non-selective-%C3%AE-blockers-is-associated-with-decreased-tumor-proliferative-indices-in-early-stage-breast-cancer
#4
Alexa Montoya, Clarissa N Amaya, Andres Belmont, Nabih Diab, Richard Trevino, Geri Villanueva, Steven Rains, Luis A Sanchez, Nabeel Badri, Salman Otoukesh, Ali Khammanivong, Danielle Liss, Sarah T Baca, Renato J Aguilera, Erin B Dickerson, Alireza Torabi, Alok K Dwivedi, Aamer Abbas, Karinn Chambers, Brad A Bryan, Zeina Nahleh
Previous studies suggest beta-adrenergic receptor (β-AR) antagonists (β-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of β1-AR and β3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor proliferation. Our analysis revealed that non-selective β-blockers, but not selective β-blockers, reduced tumor proliferation by 66% (p < 0...
December 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031160/myelo-erythroid-commitment-after-burn-injury-is-under-beta-adrenergic-control-via-mafb-regulation
#5
Shirin Hasan, Nicholas B Johnson, Michael J Mosier, Ravi Shankar, Peggie Conrad, Andrea Szilagyi, Richard L Gamelli, Kuzhali Muthumalaiappan
Severely injured burn patients receive multiple blood transfusions for anemia of critical illness despite the adverse consequences. One limiting factor to consider alternate treatment strategies is the lack of a reliable test platform to study molecular mechanisms of impaired erythropoiesis. This study illustrates how conditions resulting in high catecholamine microenvironment such as burns can instigate myelo-erythroid reprioritization influenced by beta-adrenergic stimulation leading to anemia. In mouse model of scald burn injury we observed, along with a 3-fold increase in bone marrow LSKs (lin(neg) Sca1(+)cKit(+)), the myeloid shift is accompanied with a significant reduction in megakaryocyte erythrocyte progenitors (MEPs)...
December 28, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28018974/hypoxia-sensing-through-%C3%AE-adrenergic-receptors
#6
Hoi I Cheong, Kewal Asosingh, Olivia R Stephens, Kimberly A Queisser, Weiling Xu, Belinda Willard, Bo Hu, Josephine Kam Tai Dermawan, George R Stark, Sathyamangla V Naga Prasad, Serpil C Erzurum
Life-sustaining responses to low oxygen, or hypoxia, depend on signal transduction by HIFs, but the underlying mechanisms by which cells sense hypoxia are not completely understood. Based on prior studies suggesting a link between the β-adrenergic receptor (β-AR) and hypoxia responses, we hypothesized that the β-AR mediates hypoxia sensing and is necessary for HIF-1α accumulation. Beta blocker treatment of mice suppressed hypoxia induction of renal HIF-1α accumulation, erythropoietin production, and erythropoiesis in vivo...
December 22, 2016: JCI Insight
https://www.readbyqxmd.com/read/28018228/myofilament-calcium-sensitivity-role-in-regulation-of-in-vivo-cardiac-contraction-and-relaxation
#7
REVIEW
Jae-Hoon Chung, Brandon J Biesiadecki, Mark T Ziolo, Jonathan P Davis, Paul M L Janssen
Myofilament calcium sensitivity is an often-used indicator of cardiac muscle function, often assessed in disease states such as hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). While assessment of calcium sensitivity provides important insights into the mechanical force-generating capability of a muscle at steady-state, the dynamic behavior of the muscle cannot be sufficiently assessed with a force-pCa curve alone. The equilibrium dissociation constant (Kd) of the force-pCa curve depends on the ratio of the apparent calcium association rate constant (kon) and apparent calcium dissociation rate constant (koff) of calcium on TnC and as a stand-alone parameter cannot provide an accurate description of the dynamic contraction and relaxation behavior without the additional quantification of kon or koff, or actually measuring dynamic twitch kinetic parameters in an intact muscle...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/28009703/transient-receptor-potential-vanilloid-2-function-regulates-cardiac-hypertrophy-via-stretch-induced-activation
#8
Sheryl E Koch, Adrien Mann, Shannon Jones, Nathan Robbins, Abdullah Alkhattabi, Mariah C Worley, Xu Gao, Valerie M Lasko-Roiniotis, Rajiv Karani, Logan Fulford, Min Jiang, Michelle Nieman, John N Lorenz, Jack Rubinstein
OBJECTIVE: Hypertension (increased afterload) results in cardiomyocyte hypertrophy leading to left ventricular hypertrophy and subsequently, heart failure with preserved ejection fraction. This study was performed to test the hypothesis that transient receptor potential vanilloid 2 subtype (TRPV2) function regulates hypertrophy under increased afterload conditions. METHODS: We used functional (pore specific) TRPV2 knockout mice to evaluate the effects of increased afterload-induced stretch on cardiac size and function via transverse aortic constriction (TAC) as well as hypertrophic stimuli including adrenergic and angiotensin stimulation via subcutaneous pumps...
December 22, 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/28002512/pharmacotoxicological-screening-on-new-derivatives-of-beta-phenylethylamine-potential-agonists-of-beta3-adrenergic-receptors
#9
Simona Negreş, Anca Zanfirescu, Floriana Elvira Ionică, Elena Moroşan, Bruno Ştefan Velescu, Oana Cristina Şeremet, Cristina Elena Zbârcea, Emil Ştefănescu, Manuella Militaru, Andreea LetiŢia Arsene, Denisa Marilena Margină, Livia Uncu, Corina Scutari, Cornel ChiriŢă
BACKGROUND AND AIMS: Beta3-adrenergic receptors (beta3-ARs) have been initially characterized in 1989. Afterwards, their tissue distribution was established: white and brown adipose tissue, central nervous system, myocardium (atrial and ventricular), blood vessels, smooth gastrointestinal muscles (stomach, small intestine, colon), gallbladder, urinary bladder, prostate, skeletal muscles. Non-clinical trials have demonstrated the major implication of beta3-ARs in glucose metabolism, implicitly, in insulin release, and also in obesity...
2016: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/27999715/secretory-paraspinal-paraganglioma-of-thoracolumar-spine-case-report-and-review-of-literature
#10
Saad Akhtar, Sidra Sattar, Ehsan Bari, Naila Kayani, Sarosh Moeen
BACKGROUND: Pheochromocytomas are catecholamine secreting tumors of the adrenal medulla chromaffin cells, however, when present extra-adrenally they are called paragangliomas. Paragangliomas rarely produce catecholamine in excess, which is evident by clinical symptoms, urine, and blood biochemistry. Total resection of these tumors can lead to complete clinical and biochemical resolution. This case report presents the clinical features, radiological findings, and neurological outcome in a middle-aged female with a secretory paraganglioma...
2016: Surgical Neurology International
https://www.readbyqxmd.com/read/27990717/the-first-in-man-randomized-trial-of-a-beta3-adrenoceptor-agonist-in-chronic-heart-failure-the-beat-hf-trial
#11
Henning Bundgaard, Anna Axelsson, Jakob Hartvig Thomsen, Mathias Sørgaard, Klaus F Kofoed, Rasmus Hasselbalch, Natasha A S Fry, Nana Valeur, Søren Boesgaard, Finn Gustafsson, Lars Køber, Kasper Iversen, Helge H Rasmussen
AIMS: The third isotype of beta adrenergic receptors (β3 ARs) has distinctly different effects on cardiomyocytes compared with β1 and β2 ARs. Stimulation of β3 ARs may reduce cardiomyocyte Na(+) overload and reduce oxidative stress in heart failure (HF). We examined if treatment with the β3 AR agonist mirabegron increases LVEF in patients with HF. METHODS AND RESULTS: In a double-blind trial we randomly assigned 70 patients with NYHA class II-III HF and LVEF <40% at screening-echocardiography to receive mirabegron or placebo for 6 months as add-on to optimized standard therapy...
December 18, 2016: European Journal of Heart Failure
https://www.readbyqxmd.com/read/27987017/life-in-the-fat-lane-seasonal-regulation-of-insulin-sensitivity-food-intake-and-adipose-biology-in-brown-bears
#12
K S Rigano, J L Gehring, B D Evans Hutzenbiler, A V Chen, O L Nelson, C A Vella, C T Robbins, H T Jansen
Grizzly bears (Ursus arctos horribilis) have evolved remarkable metabolic adaptations including enormous fat accumulation during the active season followed by fasting during hibernation. However, these fluctuations in body mass do not cause the same harmful effects associated with obesity in humans. To better understand these seasonal transitions, we performed insulin and glucose tolerance tests in captive grizzly bears, characterized the annual profiles of circulating adipokines, and tested the anorectic effects of centrally administered leptin at different times of the year...
December 16, 2016: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/27986616/thermogenesis-fatty-acid-synthesis-with-oxidation-and-inflammation-in-the-brown-adipose-tissue-of-ob-ob-mice
#13
Fabiane Ferreira Martins, Thereza Cristina Lonzetti Bargut, Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda
Brown adipose tissue (BAT) is specialized in heat production, but its metabolism in ob/ob mice is still a matter of debate. We aimed to verify ob/ob mice BAT using C57Bl/6 male mice (as the wild-type, WT) and leptin-deficient ob/ob mice (on the C57Bl/6 background strain), at three months of age (n=10/group). At euthanasia, animals had their interscapular BAT weighed, and prepared for analysis (Western blot, and RT-qPCR). In comparison with the WT group, the ob/ob group showed reduced thermogenic signaling markers (gene expression of beta 3-adrenergic receptor, beta3-AR; PPARgamma coactivator 1 alpha, PGC1alpha, and uncoupling protein 1, UCP1)...
December 13, 2016: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/27984527/agomelatine-a-new-opportunity-to-reduce-neuropathic-pain-preclinical-evidence
#14
Chouki Chenaf, Eric Chapuy, Frédéric Libert, Fabien Marchand, Christine Courteix, Marianne Bertrand, Cecilia Gabriel, Elisabeth Mocaër, Alain Eschalier, Nicolas Authier
Antidepressants are first-line treatments of neuropathic pain but not all these drugs are really effective. Agomelatine is an antidepressant with a novel mode of action, acting as an MT1/MT2 melatonergic receptor agonist and a 5-HT2C receptor antagonist that involves indirect norepinephrine release. Melatonin, serotonin, and norepinephrine have been involved in the pathophysiology of neuropathic pain. Yet, no study has been conducted to determine agomelatine effects on neuropathic pain in animal models. Using 3 rat models of neuropathic pain of toxic (oxaliplatin/OXA), metabolic (streptozocin/STZ), and traumatic (sciatic nerve ligation/CCI [chronic constriction nerve injury]) etiologies, we investigated the antihypersensitivity effect of acute and repeated agomelatine administration...
January 2017: Pain
https://www.readbyqxmd.com/read/27984052/beta-adrenergic-receptor-blockers-in-hypertension-alive-and-well
#15
William H Frishman
βeta-Adrenergic receptor blockers (β-blockers) are an appropriate treatment for patients having systemic hypertension (HTN) who have concomitant ischemic heart disease (IHD), heart failure, obstructive cardiomyopathy, aortic dissection or certain cardiac arrhythmias. β-blockers can be used in combination with other antiHTN drugs to achieve maximal blood pressure control. Labetalol can be used in HTN emergencies and urgencies. β-blockers may be useful in HTN patients having a hyperkinetic circulation (palpitations, tachycardia, HTN, and anxiety), migraine headache, and essential tremor...
October 27, 2016: Progress in Cardiovascular Diseases
https://www.readbyqxmd.com/read/27981180/enhancement-of-striatum-dependent-memory-by-conditioned-fear-is-mediated-by-beta-adrenergic-receptors-in-the-basolateral-amygdala
#16
Travis D Goode, Kah-Chung Leong, Jarid Goodman, Stephen Maren, Mark G Packard
Emotional arousal can have a profound impact on various learning and memory processes. For example, unconditioned emotional stimuli (e.g., predator odor or anxiogenic drugs) enhance dorsolateral striatum (DLS)-dependent habit memory. These effects critically depend on a modulatory role of the basolateral complex of the amygdala (BLA). Recent work indicates that, like unconditioned emotional stimuli, exposure to an aversive conditioned stimulus (CS) (i.e., a tone previously paired with shock) can also enhance consolidation of DLS-dependent habit memory...
June 2016: Neurobiology of Stress
https://www.readbyqxmd.com/read/27979692/therapeutic-potential-and-limitations-of-cholinergic-anti-inflammatory-pathway-in-sepsis
#17
REVIEW
Alexandre Kanashiro, Fabiane Sônego, Raphael G Ferreira, Fernanda V S Castanheira, Caio A Leite, Vanessa F Borges, Daniele C Nascimento, David F Cólon, José Carlos Alves-Filho, Luis Ulloa, Fernando Q Cunha
Sepsis is one of the main causes of mortality in hospitalized patients. Despite the recent technical advances and the development of novel generation of antibiotics, severe sepsis remains a major clinical and scientific challenge in modern medicine. Unsuccessful efforts have been dedicated to the search of therapeutic options to treat the deleterious inflammatory components of sepsis. Recent findings on neuronal networks controlling immunity raised expectations for novel therapeutic strategies to promote the regulation of sterile inflammation, such as autoimmune diseases...
December 12, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27957711/the-role-of-beta-blockers-in-the-treatment-of-hypertension
#18
John M Cruickshank
IMPORTANCE: Two major guide-line committees (JNC-8 and NICE UK) have dropped beta-blockers as first-line therapy in the treatment of hypertension. Also, recent meta-analyses (that do not take age into account) have concluded that beta-blockers are inappropriate first-line agents in the treatment of hypertension. This review seeks to shed some light on the "rights and wrongs" of such actions and conclusions. OBJECTIVES: Because the pathophysiology of primary/essential hypertension differs in elderly and younger subjects, the latter being closely linked to obesity and increased sympathetic nerve activity, the author sought to clarify the efficacy of beta-blockers in the younger/middle-aged group in reducing the risk of death, and cardiovascular end-points...
December 13, 2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27957701/autonomic-cardiovascular-control-and-executive-function-in-chronic-hypotension
#19
Stefan Duschek, Alexandra Hoffmann, Gustavo A Reyes Del Paso, Ulrich Ettinger
BACKGROUND: Chronic low blood pressure (hypotension) is characterized by complaints such as fatigue, reduced drive, dizziness, and cold limbs. Additionally, deficits in attention and memory have been observed. Autonomic dysregulation is considered to be involved in the origin of this condition. PURPOSE: The study explored autonomic cardiovascular control in the context of higher cognitive processing (executive function) in hypotension. METHODS: Hemodynamic recordings were performed in 40 hypotensive and 40 normotensive participants during execution of four classical executive function tasks (number-letter task, n-back task, continuous performance test, and flanker task)...
December 12, 2016: Annals of Behavioral Medicine: a Publication of the Society of Behavioral Medicine
https://www.readbyqxmd.com/read/27929541/non-amyloidogenic-effects-of-%C3%AE-2-adrenergic-agonists-implications-for-brimonidine-mediated-neuroprotection
#20
Shereen Nizari, Li Guo, Benjamin M Davis, Eduardo M Normando, Joana Galvao, Lisa A Turner, Mukhtar Bizrah, Mohammad Dehabadi, Kailin Tian, M Francesca Cordeiro
The amyloid beta (Aβ) pathway is strongly implicated in neurodegenerative conditions such as Alzheimer's disease and more recently, glaucoma. Here, we identify the α2 adrenergic receptor agonists (α2ARA) used to lower intraocular pressure can prevent retinal ganglion cell (RGC) death via the non-amyloidogenic Aβ-pathway. Neuroprotective effects were confirmed in vivo and in vitro in different glaucoma-related models using α2ARAs brimonidine (BMD), clonidine (Clo) and dexmedetomidine. α2ARA treatment significantly reduced RGC apoptosis in experimental-glaucoma models by 97...
December 8, 2016: Cell Death & Disease
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