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https://www.readbyqxmd.com/read/28530234/n-alkylated-analogs-of-4-methylamphetamine-4-ma-differentially-affect-monoamine-transporters-and-abuse-liability
#1
Ernesto Solis, John S Partilla, Farhana Sakloth, Iwona Ruchala, Kathryn L Schwienteck, Louis J De Felice, Jose M Eltit, Richard A Glennon, S Stevens Negus, Michael H Baumann
Clandestine chemists synthesize novel stimulant drugs by exploiting structural templates known to target monoamine transporters for dopamine, norepinephrine and serotonin (DAT, NET, and SERT, respectively). 4-Methylamphetamine (4-MA) is an emerging drug of abuse that interacts with transporters, but limited structure-activity data are available for its analogs. Here we employed uptake and release assays in rat brain synaptosomes, voltage-clamp current measurements in cells expressing transporters, and calcium flux assays in cells co-expressing transporters and calcium channels to study the effects of increasing N-alkyl chain length of 4-MA on interactions at DAT, NET and SERT...
May 22, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28529072/rescue-of-il-1%C3%AE-induced-reduction-of-human-neurogenesis-by-omega-3-fatty-acids-and-antidepressants
#2
Alessandra Borsini, Silvia Alboni, Mark A Horowitz, Luis M Tojo, Giuseppe Cannazza, Kuan-Pin Su, Carmine M Pariante, Patricia A Zunszain
Both increased inflammation and reduced neurogenesis have been associated with the pathophysiology of major depression. We have previously described how interleukin-1 (IL-1) β,a pro-inflammatory cytokine increased in depressed patients, decreases neurogenesis in human hippocampal progenitor cells. Here, using the same human in vitro model, we show how omega-3 (ω-3) polyunsaturated fatty acids and conventional antidepressants reverse this reduction in neurogenesis, while differentially affecting the kynurenine pathway...
May 18, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28528561/angiotensin-ii-for-the-treatment-of-vasodilatory-shock
#3
Ashish Khanna, Shane W English, Xueyuan S Wang, Kealy Ham, James Tumlin, Harold Szerlip, Laurence W Busse, Laith Altaweel, Timothy E Albertson, Caleb Mackey, Michael T McCurdy, David W Boldt, Stefan Chock, Paul J Young, Kenneth Krell, Richard G Wunderink, Marlies Ostermann, Raghavan Murugan, Michelle N Gong, Rakshit Panwar, Johanna Hästbacka, Raphael Favory, Balasubramanian Venkatesh, B Taylor Thompson, Rinaldo Bellomo, Jeffrey Jensen, Stew Kroll, Lakhmir S Chawla, George F Tidmarsh, Adam M Deane
Background Vasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition. Methods We randomly assigned patients with vasodilatory shock who were receiving more than 0.2 μg of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors...
May 21, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28527874/pressor-support-during-a-jarisch-herxheimer-reaction-after-initiation-of-treatment-for-weil-s-disease
#4
Randi Connor-Schuler, Anee Khan, Nikhil Goyal, Erin Zimny
We present a case of Weil's disease complicated by a Jarisch-Herxheimer reaction (JHR) after initiation of antibiotics while in the emergency department requiring invasive monitoring and vasopressor support. The case is followed by a brief review of the JHR which is rarely observed with treatment of leptospirosis. A healthy 28-year-old female who recently returned from the Caribbean presented to the emergency department with flu-like symptoms. The patient appeared jaundiced with conjunctival suffusion and was ultimately treated with the appropriate antibiotics for leptospirosis in the ED...
April 27, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28526557/the-frog-skin-host-defense-peptide-frenatin-2-1s-enhances-recruitment-activation-and-tumoricidal-capacity-of-nk-cells
#5
Jelena M Pantic, Ivan P Jovanovic, Gordana D Radosavljevic, Nevena M Gajovic, Nebojsa N Arsenijevic, J Michael Conlon, Miodrag L Lukic
Frog skin is a source of peptides with various biological properties. Frenatin 2.1S, derived from norepinephrine-stimulated skin secretions of the Orinoco lime tree frog Sphaenorhynchus lacteus, exhibits immunostimulatory effects as demonstrated by the promotion of proinflammatory phenotypes of mononuclear cells in mouse peritoneal cavity and spleen. The aim of this study was to identify the populations of host cells sensitive to the action of frenatin 2.1S in vivo and to study its effects on their functional antitumor capacity...
May 16, 2017: Peptides
https://www.readbyqxmd.com/read/28524032/-preoperative-risk-factors-analysis-of-pulmonary-hypertension-crisis-during-perioperative-period-for-caesarean-section-of-woman-with-severe-pulmonary-hypertension
#6
Chunlei Zhang, Yaguang Liu, Enming Qing, Jun Ma
OBJECTIVE: To analyze preoperative risk factors of perioperative pulmonary hypertension crisis (PHC) for pregnant woman with severe pulmonary artery hypertension (PAH), and approach its clinical value. METHODS: A retrospective analysis was conducted. The clinical data from 152 pregnant women with severe PAH underwent cesarean delivery admitted to Beijing Anzhen Hospital from January 1st 2008 to December 31st 2016 was collected. The patients were divided into two groups according to with perioperative PHC or not...
May 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28522796/effects-of-%C3%AE-adrenoceptor-and-catechol-o-methyl-transferase-comt-polymorphism-on-postoperative-outcome-in-cardiac-surgery-patients
#7
Stefan Dhein, Pascal M Dohmen, Matthias Sauer, Julia Tews, Johannes Weickmann, Anne-Kathrin Funkat, Martin Misfeld, Michael A Borger, Friedrich W Mohr
BACKGROUND There is a long-standing debate about the role of beta-adrenoceptor polymorphisms in the cardiovascular system. We wanted to elucidate whether β1-adrenoceptor-polymorphisms affects the postoperative catecholamine consumption and the length of intermediate care unit stay in patients undergoing cardiac surgery, and whether this might be enhanced or attenuated by catechol-O-methyl-transferase (COMT) polymorphism. MATERIAL AND METHODS We included 116 patients (63±1.2 years; 34% females; 81±1 kg) undergoing cardiac surgery...
May 19, 2017: Medical Science Monitor Basic Research
https://www.readbyqxmd.com/read/28522107/differences-in-neurohumoral-and-hemodynamic-response-to-prolonged-head-up-tilt-between-patients-with-high-and-normal-standing-norepinephrine-forms-of-postural-orthostatic-tachycardia-syndrome
#8
Luka Crnošija, Magdalena Krbot Skorić, Mila Lovrić, Anamari Junaković, Vladimir Miletić, Rujana Šprljan Alfirev, Antun Pavelić, Ivan Adamec, Mario Habek
OBJECTIVE: To investigate the optimal timing for blood sample collection of catecholamines and the possible correlations between neurohumoral and hemodynamic responses to prolonged head-up tilt (HUT) in postural orthostatic tachycardia syndrome (POTS). METHODS: Nineteen patients underwent a 30-minute, 70° HUT test. Blood samples (norepinephrine (NE), epinephrine and dopamine) were taken in the 10th minute of supine, and 10th, 20th and 30th minutes of HUT. RESULTS: There were no significant differences in the proportion of high and normal standing NE patients in the different time points...
May 11, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28522087/mazindol-a-risk-factor-for-pulmonary-arterial-hypertension
#9
Eric Konofal, Cherine Benzouid, Christophe Delclaux, Michel Lecendreux, Elizabeth Hussey
Mazindol is an imidazo-isoindole derivative, a tricyclic compound and a non-amphetamine central nervous system stimulant that blocks dopamine and norepinephrine reuptake. Mazindol was withdrawn from the US and European markets in 1999 for reasons unrelated to its efficacy or safety around a time when other anorexic drugs were found to be associated with the development of pulmonary arterial hypertension (PAH). Despite the use of mazindol for decades, reports of PAH due to mazindol intake have been extremely rare...
June 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28521865/exaggerated-glucagon-responses-to-hypoglycemia-in-women-with-polycystic-ovary-syndrome
#10
Susan Sam, Priyathama Vellanki, Sudha K Yalamanchi, Richard N Bergman, Andrea Dunaif
CONTEXT: Premenopausal women have blunted counter-regulatory hormone responses (CRR) to hypoglycemia compared to men. Postmenopausal women have CRR similar to men; the premenopausal pattern can be restored by estrogen. However, glucagon and pancreatic polypeptide (PP) responses remain lower in postmenopausal women than in men. Since hyperandrogenemia contributes to the metabolic phenotype of polycystic ovary syndrome (PCOS), we hypothesize that CRR to hypoglycemia especially of glucagon and PP is exaggerated in premenopausal women with PCOS compared to premenopausal control women...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28515684/selegiline-ameliorates-depression-like-behavior-in-mice-lacking-the-cd157-bst1-gene-a-risk-factor-for-parkinson-s-disease
#11
Satoka Kasai, Toru Yoshihara, Olga Lopatina, Katsuhiko Ishihara, Haruhiro Higashida
Parkinson's disease (PD), a neurodegenerative disorder, is accompanied by various non-motor symptoms including depression and anxiety, which may precede the onset of motor symptoms. Selegiline is an irreversible monoamine oxidase-B (MAO-B) inhibitor, and is widely used in the treatment of PD and major depression. However, there are few reports about the effects of selegiline on non-motor symptoms in PD. The aim of this study was to explore the antidepressant and anxiolytic effects of selegiline, using CD157/BST1 knockout (CD157 KO) mouse, a PD-related genetic model displaying depression and anxiety, compared with other antiparkinsonian drugs and an antidepressant, and was to investigate the effects of selegiline on biochemical parameters in emotion-related brain regions...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28512154/glucose-autoregulation-is-the-dominant-component-of-the-hormone-independent-counterregulatory-response-to-hypoglycemia-in-the-conscious-dog
#12
Justin M Gregory, Noelia Rivera, Guillaume Kraft, Jason J Winnick, Ben Farmer, Eric J Allen, E Patrick Donahue, Marta S Smith, Dale S Edgerton, Phillip E Williams, Alan D Cherrington
The contribution of hormone-independent counterregulatory signals in defense of insulin-induced hypoglycemia were determined in adrenalectomized, overnight-fasted conscious dogs receiving hepatic portal vein insulin infusions at a rate 20-fold basal. Either euglycemia was maintained (group 1) or hypoglycemia (≈45 mg/dL) was allowed to occur. There were 3 hypoglycemic groups: one in which hepatic autoregulation against hypoglycemia occurred in the absence of sympathetic nervous system input (group 2), autoregulation in the presence of norepinephrine (NE) signaling to fat and muscle (group 3), and autoregulation in the presence of NE signaling to fat, muscle, and liver (group 4)...
May 16, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28509668/norepinephrine-in-septic-shock-when-and-how-much
#13
Olfa Hamzaoui, Thomas W L Scheeren, Jean-Louis Teboul
PURPOSE OF REVIEW: Norepinephrine is the first-line agent recommended during resuscitation of septic shock to correct hypotension because of depressed vascular tone. Important clinical issues are the best timing to start norepinephrine, the optimal blood pressure target, and the best therapeutic options to face refractory hypotension of when high doses of norepinephrine are required to reach the target. RECENT FINDINGS: Recent literature has reported benefits of early administration of norepinephrine because of the following reasons: profound and durable hypotension is an independent factor of increased mortality, early administration of norepinephrine increases cardiac output, improves microcirculation and avoid fluid overload...
May 13, 2017: Current Opinion in Critical Care
https://www.readbyqxmd.com/read/28508370/a-proteomic-evaluation-of-sympathetic-activity-biomarkers-of-the-hypothalamus-pituitary-adrenal-axis-by-western-blotting-technique-following-experimental-traumatic-brain-injury
#14
Hale Zerrin Toklu, Yasemin Sakarya, Nihal Tümer
Endocrine disorders and autonomic dysfunction are common paradigms following traumatic brain injury (TBI). Alterations in the hypothalamus-pituitary-adrenal (HPA) axis following TBI may result in impaired vasopressor response, energy imbalance, fatigue, depression, or neurological disorders. Autonomic dysfunction is a common disorder following TBI. The sympathetic activity markers on HPA axis can be measured by Western blot protein analysis. Tyrosine hydroxylase, dopamine beta hydroxylase are the key enzymes for the synthesis of norepinephrine; and neuropeptide Y (NPY) is the peptide that is co-stored and co-released with norepinephrine...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28507531/noradrenergic-activation-of-hypoglossal-nucleus-modulates-the-central-regulation-of-genioglossus-in-chronic-intermittent-hypoxic-rats
#15
Xinshi Nie, Ling Zhou, Aidi Wang, Hongyu Jin, Zheng Qin, Jian Pang, Wei Wang, Jian Kang
Neuromuscular compensation of the genioglossus muscle can be induced by chronic intermittent hypoxia (CIH) in obstructive sleep apnea to maintain upper airway stability. Noradrenergic activation of hypoglossal nucleus plays a critical role in the central control of the genioglossus. However, it remains unknown whether norepinephrine takes part in the central regulation of the genioglossus during CIH. Adult male Wistar rats (n = 32) were studied to explore the influence of noradrenergic activation of hypoglossal nucleus on the central control of the genioglossus at different stages of CIH...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28507504/effects-of-%C3%AE-2a-adrenoceptors-on-norepinephrine-secretion-from-the-locus-coeruleus-during-chronic-stress-induced-depression
#16
Bin Wang, Ying Wang, Qiong Wu, Hong-Ping Huang, Shao Li
Chronic stressors can often lead to the development of psychological disorders, such as depression and anxiety. The locus coeruleus (LC) is a stress sensitive brain region located in the pons, with noradrenergic neurons that project to the hypothalamus, especially the paraventricular nucleus (PVN) of the hypothalamus. The purpose of this paper is to better understand how alpha 2A-adrenoceptors (α2A-ARs) and LC-hypothalamus noradrenergic system participate in the pathophysiological mechanism of depression. In vivo norepinephrine (NE) release in the PVN triggered by electrical stimulation in the LC was detected with carbon fiber electrodes in depression model of rats induced by chronic unpredictable mild stress (CUMS)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28507335/bnip3l-promotes-cardiac-fibrosis-in-cardiac-fibroblasts-through-ca-2-i-tgf-%C3%AE-smad2-3-pathway
#17
Weili Liu, Xinxing Wang, Zhusong Mei, Jingbo Gong, Lishuang Huang, Xiujie Gao, Yun Zhao, Jing Ma, Lingjia Qian
Fibrosis is an important, structurally damaging event that occurs in pathological cardiac remodeling, leading to cardiac dysfunction. BNIP3L is up-regulated in pressure overload-induced heart failure and has been reported to play an important role in cardiomyocyte apoptosis; however, its involvement in cardiac fibroblasts (CFs) remains unknown. We prove for the first time that the expression of BNIP3L is significantly increased in the CFs of rats undergoing pressure overload-induced heart failure. Furthermore, this increased BNIP3L expression was confirmed in cultured neonatal rat CFs undergoing proliferation and extracellular matrix (ECM) protein over-expression that was induced by norepinephrine (NE)...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28505064/changes-in-renal-artery-dimensions-are-associated-with-clinical-response-to-radiofrequency-renal-denervation-a-series-of-studies-using-quantitative-angiography-and-intravascular-ultrasound
#18
Thomas Weber, Jörg Kellermair, Karen T Witberg, Jurgen Ligthart, Robert J Melder, Thomas Forstner, Bernd Eber
OBJECTIVE: Renal denervation (RDN) can cause focal (notches) and global (spasms) changes in renal artery dimensions. We quantified these changes and related them to renal norepinephrin tissue content in animals and to blood pressure (BP) changes in patients. METHODS: We measured renal artery dimensions pre-RDN and post-RDN, utilizing quantitative renal angiography (QRA) in a porcine model and in a retrospective patient cohort, and intravascular ultrasound (IVUS) in a prospective patient cohort...
May 12, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28504408/kv1-3-channels-facilitate-the-connection-between-metabolism-and-blood-flow-in-the-heart
#19
REVIEW
Vahagn Ohanyan, Liya Yin, Raffi Bardakjian, Christopher Kolz, Molly Enrick, Tatevik Hakobyan, Jordan Luli, Kathleen Graham, Mohamed Khayata, Suzanna Logan, John Kmetz, William M Chilian
The connection between metabolism and flow in the heart, metabolic dilation, is essential for cardiac function. We recently found redox-sensitive Kv1.5 channels play a role in coronary metabolic dilation; however, more than one ion channel likely plays a role in this process as animals null for these channels still showed limited coronary metabolic dilation. Accordingly, we examined the role of another Kv1 family channel, the energetically linked Kv1.3 channel, in coronary metabolic dilation. We measured myocardial blood flow (contrast echocardiography) during norepinephrine-induced increases in cardiac work (heart rate x mean arterial pressure) in WT, WT mice given correolide (preferential Kv1...
May 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28503727/serotonin-norepinephrine-reuptake-inhibitors-and-the-influence-of-binding-affinity-ki-on-analgesia
#20
M Raouf, A J Glogowski, J J Bettinger, J Fudin
WHAT IS KNOWN AND OBJECTIVE: Serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly used for various psychiatric conditions and neuropathic pain syndromes. SNRIs inhibit the reuptake of serotonin (5-HT) and norepinephrine (NE); however, NE reuptake inhibition is thought to be the primary mediator for their analgesic effect. COMMENT: Key differences in pharmacodynamics and receptor affinities exist between SNRIs. The selectivity for each monoamine differs among SNRIs based on the agent's affinity and activity at the monoamine reuptake transporter...
May 15, 2017: Journal of Clinical Pharmacy and Therapeutics
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