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https://www.readbyqxmd.com/read/28105598/clinical-pharmacokinetics-and-pharmacodynamics-of-dexmedetomidine
#1
REVIEW
Maud A S Weerink, Michel M R F Struys, Laura N Hannivoort, Clemens R M Barends, Anthony R Absalom, Pieter Colin
Dexmedetomidine is an α2-adrenoceptor agonist with sedative, anxiolytic, sympatholytic, and analgesic-sparing effects, and minimal depression of respiratory function. It is potent and highly selective for α2-receptors with an α2:α1 ratio of 1620:1. Hemodynamic effects, which include transient hypertension, bradycardia, and hypotension, result from the drug's peripheral vasoconstrictive and sympatholytic properties. Dexmedetomidine exerts its hypnotic action through activation of central pre- and postsynaptic α2-receptors in the locus coeruleus, thereby inducting a state of unconsciousness similar to natural sleep, with the unique aspect that patients remain easily rousable and cooperative...
January 19, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28103158/serotonin-receptor-targeted-therapy-for-migraine-treatment-an-overview-of-drugs-in-phase-i-and-ii-clinical-development
#2
P Barbanti, C Aurilia, G Egeo, L Fofi, R Palmirotta
Research has focused on serotonin (5-HT) 5-HT1D and 5-HT1F receptors to develop drugs acting through non-vasoconstrictive mechanisms for treating acute migraine and those targeting 5-HT2B and 5-HT7 receptors for preventing migraine. Areas covered: This paper reviews antimigraine drugs targeting 5-HT receptors in one phase I trial (sumatriptan iontophoretic transdermal system, TDS) and five phase II clinical trials (PNU-142633, LY334370, lasmiditan, NOX-188). Expert opinion: Data from our overview on investigational drugs in phase I and II clinical trials using the 5-HT1B/1D receptor agonist (sumatriptan TDS), 5-HT1D receptor agonist (PNU-142633), 5-HT1F receptor agonists (LY334370, lasmiditan) and a combined 5-HT1B/1D receptor agonist with nNOS inhibition (NOX-188) provided encouraging data for sumatriptan TDS and lasmiditan, disappointing results for PNU-142633, and promising findings for NOX-188...
January 19, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28102435/effects-of-tryptophan-containing-peptides-on-angiotensin-converting-enzyme-activity-and-vessel-tone-ex-vivo-and-in-vivo
#3
Sherif Khedr, Andreas Deussen, Irakli Kopaliani, Birgit Zatschler, Melanie Martin
PURPOSE: Over-activation of the renin-angiotensin axis and worsening of vascular function are critical contributors to the development of hypertension. Therefore, inhibition of angiotensin-converting enzyme (ACE), a key factor of the renin-angiotensin axis, is a first line treatment of hypertension. Besides pharmaceutical ACE inhibitors, some natural peptides have been shown to exert ACE-inhibiting properties with antihypertensive effects and potentially beneficial effects on vascular function...
January 19, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28101178/endothelium-dependent-vasodilation-effects-of-panax-notoginseng-and-its-main-components-are-mediated-by-nitric-oxide-and-cyclooxygenase-pathways
#4
Yanyan Wang, Yu Ren, Leilei Xing, Xiangdong Dai, Sheng Liu, Bin Yu, Yi Wang
Panax notoginseng, a traditional Chinese herbal medicine, has been used for the treatment of cardiovascular diseases. The main bioactive components of this species are Panax notoginseng saponins (PNS). The present study aimed to investigate the effects of PNS and five of its main components (ginsenosides Rg1, Re, Rb1 and Rd, and notoginsenoside R1) on rat aorta rings pre-contracted with norepinephrine (NE) and to determine the underlying mechanism of action. Isolated aorta rings (with or without intact endothelium) from adult male Wistar rats were stimulated with NE to induce vasoconstriction, and subsequently treated with different concentrations of PNS and its five main components (Rg1, Re, Rb1, R1 and Rd) separately...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28101177/analysis-on-mechanism-of-atp-sensitive-k-channel-opener-natakalim-improving-congestive-heart-failure-after-myocardial-infarction
#5
Feng Jin
The action mechanism of natakalim, a novel ATP-sensitive potassium channel opener, was studied in ameliorating the congestive heart failure (CHF) after myocardial infarction. A total of 25 healthy Wistar male rats (age, 10 weeks; average weight, 300 g) were selected, and the CHF models after acute myocardial infarction (AMI) were prepared by ligation of left anterior descending branch. They were randomly divided into the sham operation group, the model group and the groups of 1, 3 and 9 mg/kg/day natakalims...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28100453/mechanisms-of-vasovagal-syncope-in-the-young-reduced-systemic-vascular-resistance-versus-reduced-cardiac-output
#6
Julian M Stewart, Marvin S Medow, Richard Sutton, Paul Visintainer, David L Jardine, Wouter Wieling
BACKGROUND: Syncope is a sudden transient loss of consciousness and postural tone caused by cerebral hypoperfusion. The most common form is vasovagal syncope (VVS). Presyncopal progressive early hypotension in older VVS patients is caused by reduced cardiac output (CO); younger patients have reduced systemic vascular resistance (SVR). Using a priori criteria for reduced CO (↓CO) and SVR (↓SVR), we studied 48 recurrent young fainters comparing subgroups of VVS with VVS-↓CO, VVS-↓SVR, and both VVS-↓CO&↓SVR...
January 18, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28100130/influence-of-cold-water-immersion-on-limb-blood-flow-after-resistance-exercise
#7
Chris Mawhinney, Helen Jones, David A Low, Daniel J Green, Glyn Howatson, Warren Gregson
This study determined the influence of cold (8°C) and cool (22°C) water immersion on lower limb and cutaneous blood flow following resistance exercise. Twelve males completed 4 sets of 10-repetition maximum squat exercise and were then immersed, semi-reclined, into 8°C or 22°C water for 10-min, or rested in a seated position (control) in a randomized order on different days. Rectal and thigh skin temperature, muscle temperature, thigh and calf skin blood flow and superficial femoral artery blood flow were measured before and after immersion...
January 19, 2017: European Journal of Sport Science
https://www.readbyqxmd.com/read/28099525/polyethylene-glycol-camouflaged-earthworm-hemoglobin
#8
Vivek P Jani, Alborz Jelvani, Selamawit Moges, Parimala Nacharaju, Camille Roche, David Dantsker, Andre Palmer, Joel M Friedman, Pedro Cabrales
Nearly 21 million components of blood and whole blood and transfused annually in the United States, while on average only 13.6 million units of blood are donated. As the demand for Red Blood Cells (RBCs) continues to increase due to the aging population, this deficit will be more significant. Despite decades of research to develop hemoglobin (Hb) based oxygen (O2) carriers (HBOCs) as RBC substitutes, there are no products approved for clinical use. Lumbricus terrestris erythrocruorin (LtEc) is the large acellular O2 carrying protein complex found in the earthworm Lumbricus terrestris...
2017: PloS One
https://www.readbyqxmd.com/read/28097528/pharmacology-and-toxicology-of-n-benzylphenethylamine-nbome-hallucinogens
#9
Adam L Halberstadt
Serotonergic hallucinogens induce profound changes in perception and cognition. The characteristic effects of hallucinogens are mediated by 5-HT2A receptor activation. One class of hallucinogens are 2,5-dimethoxy-substituted phenethylamines, such as the so-called 2C-X compounds 2,5-dimethoxy-4-bromophenethylamine (2C-B) and 2,5-dimethoxy-4-iodophenethylamine (2C-I). Addition of an N-benzyl group to phenethylamine hallucinogens produces a marked increase in 5-HT2A-binding affinity and hallucinogenic potency...
January 18, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28096303/down-regulation-of-epas1-transcription-and-genetic-adaptation-of-tibetans-to-high-altitude-hypoxia
#10
Yi Peng, Chaoying Cui, Yaoxi He, Ouzhuluobu, Hui Zhang, Deying Yang, Qu Zhang, Bianbazhuoma, Lixin Yang, Yibo He, Kun Xiang, Xiaoming Zhang, Sushil Bhandari, Peng Shi, Yangla, Dejiquzong, Baimakangzhuo, Duojizhuoma, Yongyue Pan, Cirenyangji, Baimayangji, Gonggalanzi, Caijuan Bai, Bianba, Basang, Ciwangsangbu, Shuhua Xu, Hua Chen, Shimin Liu, Tianyi Wu, Xuebin Qi, Bing Su
Tibetans are well adapted to the hypoxic environments at high altitude, yet the molecular mechanism of this adaptation remains elusive. We reported comprehensive genetic and functional analyses of EPAS1, a gene encoding hypoxia inducible factor 2α (HIF-2α) with the strongest signal of selection in previous genome-wide scans of Tibetans. We showed that the Tibetan-enriched EPAS1 variants down-regulate expression in human umbilical endothelial cells and placentas. Heterozygous EPAS1 knockout mice display blunted physiological responses to chronic hypoxia, mirroring the situation in Tibetans...
January 17, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28094441/sex-drugs-and-rock-and-roll-tales-from-preterm-fetal-life
#11
Laura Bennet
Premature fetuses and babies are at greater risk of mortality and morbidity than their term counterparts. The underlying causes are multifactorial, but include exposure to hypoxia. Immaturity of organs and their functional control may impair the physiological defence responses to hypoxia and the preterm fetal responses, or lack thereof, to moderate hypoxia appear to support this concept. However, as this review demonstrates, despite immaturity, the preterm fetus responds to asphyxia in a qualitatively similar manner to that seen at term...
January 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28093201/molecular-targets-of-the-warburg-effect-and-inflammatory-cytokines-in-the-pathogenesis-of-pulmonary-artery-hypertension
#12
REVIEW
Na Liu, Stephanie Parry, Yunbin Xiao, Shenghua Zhou, Qiming Liu
Pulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by increased pulmonary arterial pressure and vasoconstriction and structural remolding of pulmonary arterioles. Recent clinical and experimental studies have discovered the relationship between metabolic alterations and the pathogenesis of PAH. The primary metabolic alteration, previously demonstrated in various cancers, is a gradual change in energy generated from complete aerobic cellular respiration to from solely "aerobic glycolysis," termed the "Warburg effect...
January 13, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28090300/bk-channels-in-rat-and-human-pulmonary-smooth-muscle-cells-are-bk%C3%AE-%C3%AE-1-functional-complexes-lacking-the-oxygen-sensitive-stress-axis-regulated-exon-insert
#13
Neil D Detweiler, Li Song, Samantha J McClenahan, Rachel J Versluis, Sujay V Kharade, Richard C Kurten, Sung W Rhee, Nancy J Rusch
A loss of K(+) efflux in pulmonary arterial smooth muscle cells (PASMCs) contributes to abnormal vasoconstriction and PASMC proliferation during pulmonary hypertension (PH). Activation of high-conductance Ca(2+)-activated (BK) channels represents a therapeutic strategy to restore K(+) efflux to the affected PASMCs. However, the properties of BK channels in PASMCs-including sensitivity to BK channel openers (BKCOs)-are poorly defined. The goal of this study was to compare the properties of BK channels between PASMCs of normoxic (N) and chronic hypoxic (CH) rats and then explore key findings in human PASMCs...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28088737/the-hemostatic-effect-study-of-cirsium-setosum-on-regulating-%C3%AE-1-ars-via-mediating-norepinephrine-synthesis-by-enzyme-catalysis
#14
Nianwei Chang, Yanmei Li, Mengge Zhou, Jie Gao, Yuanyuan Hou, Min Jiang, Gang Bai
BACKGROUND: Cirsium setosum (CS) is the aboveground part of Cephalanoplos segetum Kitam. Although it has been used as a hemostatic treatment for thousands of years and is still in use today, the mechanism of CS on regulating ARs is still not clear. PURPOSE: In this study, we aimed to clarify the mechanism of CS on regulating ARs. METHODS: We developed a simple method based on UPLC/Q-TOF MS combined adrenergic receptor dual-luciferase reporter assay systems for the rapid determination of active constituents in CS...
January 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28087351/central-nervous-system-vasculitis-in-adults-an-update
#15
REVIEW
Lívia Almeida Dutra, Alexandre Wagner Silva de Souza, Gabriela Grinberg-Dias, Orlando Graziani Povoas Barsottini, Simone Appenzeller
Primary central nervous system vasculitis (PCNSV) is a challenging diagnosis due to broad clinical manifestations and variable specificity and sensitivity of laboratory and imaging diagnostic tools. Differential diagnosis include reversible cerebral vasoconstriction syndrome (RCVS), secondary vasculitis of the CNS and other noninflammatory vasculopathies. Brain biopsy is essential for definitive diagnosis and to exclude mimickers. Recent data show data large-vessel PCNSV present worse prognosis when compared to small-vessel PCNSV...
January 10, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28079670/impact-of-genetic-variation-in-the-vasopressin-1a-receptor-on-the-development-of-organ-failure-in-patients-admitted-for-acute-decompensation-of-liver-cirrhosis
#16
Annarein J C Kerbert, Jelte J Schaapman, Johan J van der Reijden, Àlex Amorós Navarro, Aiden McCormick, Bart van Hoek, Vicente Arroyo, Pere Ginès, Rajiv Jalan, Victor Vargas, Rudolf Stauber, Hein W Verspaget, Minneke J Coenraad
BACKGROUND: Vasopressin receptor-mediated vasoconstriction is considered to be involved in the pathogenesis of organ failure in acute-on-chronic liver failure (ACLF). PATIENTS AND METHODS: We studied the association between six single nucleotide polymorphisms (SNPs) of the vasopressin 1a receptor gene and the development of organ failure in 826 patients admitted for acute decompensation of liver cirrhosis (n=641) or ACLF (n=185). RESULTS: No associations were found for SNPs with the presence of circulatory or renal failure...
January 10, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28076702/lasmiditan-for-the-treatment-of-migraine
#17
Matilde Capi, Fernando de Andrés, Luana Lionetto, Giovanna Gentile, Fabiola Cipolla, Marina Borro, Paolo Martelletti, Martina Curto
Migraine is one of the most common diseases in the world, with high economical and subjective burden. Migraine acute therapy is nowadays based on specific and non-specific drugs but up to 40% of episodic migraineurs still have unmet treatment needs and over 35% do not benefit from triptans administration. Serotonin-1F receptors have been identified in trigeminal system and became an ideal target for anti-migraine drug development as potential trigeminal neural inhibitors. Lasmiditan, a novel serotonin1F receptor agonist, showed specific affinity in vitro for the receptor with any vasoconstrictive action and inhibited markers associated with electrical stimulation of trigeminal ganglion in migraine animal models...
January 11, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28073658/copeptin-levels-in-patients-with-vasovagal-syncope
#18
Panayota Flevari, Dionyssios Leftheriotis, Christos Kroupis, George Antonakos, John Lekakis, Kleanthi Dima
BACKGROUND AND PURPOSE: Vasovagal syncope (VVS) is linked to more than one pathophysiologic mechanisms. Copeptin, an emerging cardiovascular marker, is a surrogate for arginine-vasopressin, which increases following VVS. We aimed to assess the dynamic pattern of copeptin levels in typical VVS, categorized by the degree of vasoconstriction during orthostasis, and healthy controls. METHODS: The following groups were studied: Group A (n=21), with adequate limb vasoconstriction during the first min...
January 4, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28072557/expression-and-localization-of-the-at1-and-at2-angiotensin-ii-receptors-and-%C3%AE-1a-and-%C3%AE-1d-adrenergic-receptors-in-aorta-of-hypertensive-and-diabetic-rats
#19
Jessica Edith Rodríguez, Rodrigo Romero-Nava, Aldo Arturo Reséndiz-Albor, Erika Rosales-Cruz, Enrique Hong, Fengyang Huang, Santiago Villafaña
Hypertension and diabetes are multifactorial diseases that frequently coexist and exacerbate each another. During the development of diabetes, the impairment of noradrenergic and renin-angiotensin systems has been reported in the response mediated by α1-AR and AT1 receptors. Although their participation in the development of cardiovascular complications is still controversial, some studies have found increased or diminished response to the vasoconstrictive effect of noradrenaline or angiotensin II in a time-dependent manner of diabetes...
2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28069828/lpa1-receptor-mediated-thromboxane-a2-release-is-responsible-for-lysophosphatidic-acid-induced-vascular-smooth-muscle-contraction
#20
Péter Tibor Dancs, Éva Ruisanchez, Andrea Balogh, Cecília Rita Panta, Zsuzsanna Miklós, Rolf M Nüsing, Junken Aoki, Jerold Chun, Stefan Offermanns, Gábor Tigyi, Zoltán Benyó
Lysophosphatidic acid (LPA) has been recognized recently as an endothelium-dependent vasodilator, but several lines of evidence indicate that it may also stimulate vascular smooth muscle cells (VSMCs), thereby contributing to vasoregulation and remodeling. In the present study, mRNA expression of all 6 LPA receptor genes was detected in murine aortic VSMCs, with the highest levels of LPA1, LPA2, LPA4, and LPA6 In endothelium-denuded thoracic aorta (TA) and abdominal aorta (AA) segments, 1-oleoyl-LPA and the LPA1-3 agonist VPC31143 induced dose-dependent vasoconstriction...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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