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https://www.readbyqxmd.com/read/28642233/sembragiline-a-novel-selective-monoamine-oxidase-type-b-inhibitor-for-the-treatment-of-alzheimer-s-disease
#1
Edilio Borroni, Bernd Bohrmann, Fiona Grueninger, Eric Prinssen, Stephane Nave, Hansruedi Loetscher, Shankar J Chinta, Subramanian Rajagopalan, Anand Rane, Almas Siddiqui, Bart Ellenbroek, Juerg Messer, Axel Pahler, Julie K Anderson, Rene Wyler, Andrea M Cesura
Monoamine oxidase B (MAO-B) has been implicated in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders. Increased MAO-B expression in astroglia has been observed adjacent to amyloid plaques in AD patient brains. This phenomenon is hypothesised to lead to increased production of hydrogen peroxide and reactive oxygen species (ROS), thereby contributing to AD pathology. Therefore, reduction of ROS-induced oxidative stress via inhibition of MAO-B activity may delay the progression of the disease...
June 22, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28638005/sclerosing-mesenteritis-causing-chylous-ascites-and-small-bowel-perforation
#2
Huei-Wen Lim, Keith S Sultan
BACKGROUND Sclerosing mesenteritis (SM) is a rare idiopathic inflammation and fibrosis of the mesentery. Its etiology and pathogenesis remain unclear. It has been linked to abdominal trauma related to peritoneal dialysis, recent abdominal surgery, idiopathic inflammatory disorder, paraneoplastic syndrome, ischemia/infection, and autoimmunity. Abdominal CT is the most sensitive imaging modality, and diagnosis is usually confirmed by surgical biopsy. Patients most often present with abdominal pain, nausea, vomiting, diarrhea, and weight loss, and less commonly with chylous ascites and small bowel obstruction...
June 22, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28603038/a-cross-species-translational-pharmacokinetic-pharmacodynamic-evaluation-of-core-body-temperature-reduction-by-the-trpm8-blocker-pf-05105679
#3
James R Gosset, Kevin Beaumont, Tomomi Matsuura, Wendy Winchester, Neil Attkins, Sophie Glatt, Ian Lightbown, Kristina Ulrich, Sonia Roberts, Jolie Harris, Emir Mesic, Tamara van Steeg, Diana Hijdra, Piet H van der Graaf
PF-05105679 is a moderately potent TRPM8 blocker which has been evaluated for the treatment of cold pain sensitivity. The TRPM8 channel is responsible for the sensation of cold environmental temperatures and has been implicated in regulation of core body temperature. Consequently, blockade of TRPM8 has been suggested to result in lowering of core body temperature. As part of the progression to human studies, the effect of PF-05105679 on core body temperature has been investigated in animals. Safety pharmacology studies showed that PF-05105679 reduced core body temperature in a manner that was inversely related to body weight of the species tested (greater exposure to PF-05105679 was required to lower temperature by 1°C in higher species)...
June 7, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28601272/safety-considerations-and-guideline-based-safe-use-recommendations-for-bolus-dose-vasopressors-in-the-emergency-department
#4
Devin Holden, Jessica Ramich, Edward Timm, Denis Pauze, Timothy Lesar
The use of intermittently administered doses of vasopressors to correct hypotension in the emergency department (ED), commonly referred to as bolus-dose pressors, push-dose pressors, Neo-sticks, or phenyl sticks, has been widely advocated outside of the traditional printed medical literature. No outcomes data of this practice exist to demonstrate benefits over traditional continuous infusion of vasopressors. Use of bolus-dose vasopressors in the ED setting raises a number of patient safety concerns, and misuse and errors in the preparation and administration of bolus-dose vasopressors may result in patient harm...
June 7, 2017: Annals of Emergency Medicine
https://www.readbyqxmd.com/read/28599683/pain-sensitivity-and-analgesic-use-among-10-486-adults-the-troms%C3%A3-study
#5
Per-Jostein Samuelsen, Christopher Sivert Nielsen, Tom Wilsgaard, Audun Stubhaug, Kristian Svendsen, Anne Elise Eggen
BACKGROUND: Increased pain sensitivity is a putative risk factor for chronic pain and consequently for analgesic use. Conversely, analgesic use may be a cause of increased pain sensitivity, e.g., through opioid-induced hyperalgesia. We aimed to study the association between pain sensitivity and analgesic use in a general population, and to test the hypothesis that increased baseline pain sensitivity is a risk factor for future persistent analgesic use. METHODS: The Tromsø Study (2007-08), a population-based health study, was linked with eight years of prescription data from the Norwegian Prescription Database...
June 9, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28596676/renin-angiotensin-system-in-liver-diseases-friend-or-foe
#6
REVIEW
Ana Cristina Simões E Silva, Aline S Miranda, Natália P Rocha, Antônio L Teixeira
In the last three decades, the understanding of the renin angiotensin system (RAS) has been changed by the discoveries of functional local systems, novel biologically active peptides, additional specific receptors, alternative pathways of angiotensin (Ang) II generation, and new roles for enzymes and precursor components other than those in Ang II synthesis. In this regard, the discovery that Ang-(1-7) opposes the pressor, proliferative, pro-fibrotic, and pro-inflammatory effects mediated by Ang II has contributed to the realization that the RAS is composed of two axes...
May 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28596051/functions-of-at1-and-at2-angiotensin-receptors-in-the-paraventricular-nucleus-of-the-rat-correlating-single-unit-and-cardiovascular-responses
#7
Mehrangiz Khanmoradi, Ali Nasimi
The paraventricular hypothalamic nucleus (PVN) is a complex structure with both neuroendocrine and autonomic functions including cardiovascular control. The PVN contains angiotensin II (AngII) immunoreactive cells, fibers, as well as AT1 and AT2 receptors of AngII. We microinjected AngII into the PVN of normotensive anesthetized rats and simultaneously recorded blood pressure, heart rate (HR) and single-unit responses. The roles of AT1 and AT2 receptors in these responses were also evaluated. Microinjection of AngII into the PVN produced a short excitatory single-unit response and two types of pressor responses: short duration with a decrease in HR and long with an increase in HR...
June 6, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28573048/brain-oscillations-elicited-by-the-cold-pressor-test-a-putative-index-of-untreated-essential-hypertension
#8
Christos Papageorgiou, Efstathios Manios, Eleftheria Tsaltas, Eleni Koroboki, Maria Alevizaki, Elias Angelopoulos, Meletios-Athanasios Dimopoulos, Charalabos Papageorgiou, Nikolaos Zakopoulos
OBJECTIVE: Essential hypertension is associated with reduced pain sensitivity of unclear aetiology. This study explores this issue using the Cold Pressor Test (CPT), a reliable pain/stress model, comparing CPT-related EEG activity in first episode hypertensives and controls. METHOD: 22 untreated hypertensives and 18 matched normotensives underwent 24-hour ambulatory blood pressure monitoring (ABPM). EEG recordings were taken before, during, and after CPT exposure...
2017: International Journal of Hypertension
https://www.readbyqxmd.com/read/28553158/the-impact-of-stress-on-tournament-entry
#9
Thomas Buser, Anna Dreber, Johanna Mollerstrom
Individual willingness to enter competitive environments predicts career choices and labor market outcomes. Meanwhile, many people experience competitive contexts as stressful. We use two laboratory experiments to investigate whether factors related to stress can help explain individual differences in tournament entry. Experiment 1 studies whether stress responses (measured as salivary cortisol) to taking part in a mandatory tournament predict individual willingness to participate in a voluntary tournament...
2017: Experimental Economics
https://www.readbyqxmd.com/read/28529060/the-effect-of-anxiety-sensitivity-on-psychological-and-biological-variables-during-the-cold-pressor-test
#10
Naomi Dodo, Ryusaku Hashimoto
We examined the relationship between anxiety sensitivity (AS) and autonomic nervous system responses (ANS) during the cold pressor test (CPT). Seventy-four university students participated and were divided into low-AS (M=9.06, SD=3.97) and high-AS groups (M=28.68, SD=6.63) based on AS Index scores (n's=36 and 38, respectively). The study included three phases: Rest, CPT, and Recovery. We measured the psychological variables (fear of pain and subjective pain) at pre- and post-CPT. ANS response data were collected during each phase...
May 13, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28527874/pressor-support-during-a-jarisch-herxheimer-reaction-after-initiation-of-treatment-for-weil-s-disease
#11
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/28522759/effect-of-cyclooxygenase-inhibition-on-the-inspiratory-muscle-metaboreflex-induced-cardiovascular-consequences-in-men
#12
Joshua R Smith, Kaylin D Didier, Shane M Hammer, Andrew M Alexander, Stephanie P Kurti, Steven W Copp, Thomas J Barstow, Craig A Harms
Inspiratory muscle metaboreflex activation increases mean arterial pressure (MAP) and limb vascular resistance (LVR) and decreases limb blood flow (Q̇L). Cyclooxygenase (COX) inhibition has been found to attenuate limb skeletal muscle metaboreflex-induced increases in muscle sympathetic nerve activity. We hypothesized that compared to placebo (PLA), COX inhibition would attenuate inspiratory muscle metaboreflex-induced 1) increases in MAP and LVR and 2) decreases in Q̇L Seven men (22±1 years) were recruited and orally consumed ibuprofen (IB, 10mg/kg) or PLA 90 min prior to performing the cold pressor test (CPT) for 2 min and inspiratory resistive breathing task (IRBT) for 14...
May 18, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28521325/effect-of-high-salt-diet-on-age-related-high-blood-pressure-and-hypothalamic-redox-signaling
#13
Bilgen Basgut, Melissa A Whidden, Nataliya Kirichenko, Mary Woods, Benedek Erdos, Philip J Scarpace, Nihal Tümer
AIM: The aim of this study was to investigate the effect of a high salt (HS) diet on age-related changes in blood pressure (BP) and the possible role played by regulatory central mechanisms. METHODS: Young (5 months) and old (27 months) male Fischer 344 × Brown Norway (F344/BN) rats were fed standard chow or 8% HS diet for 12 days. BP and heart rate (HR) were measured by telemetry. RESULTS: Mean arterial BP (MAP) was significantly elevated in old rats during the day and night when compared with young animals...
May 19, 2017: Pharmacology
https://www.readbyqxmd.com/read/28508511/clinical-nociceptive-and-psychological-profiling-to-predict-acute-pain-after-total-knee-arthroplasty
#14
I E Luna, H Kehlet, M A Petersen, E K Aasvang
BACKGROUND: Pre-operative identification of high-pain responders for acute pain after total knee arthroplasty (TKA) could lead to targeted analgesic trials and individualized analgesic strategies to improve recovery and potentially reduce the risk of persistent post-surgical pain. The aim of this study was to use simple clinical tests and questionnaires to identify predictive nociceptive and psychological factors for acute post-TKA pain. METHODS: Sixty consecutive TKA patients were included in a prospective descriptive study of pain during a 5-m walk-test 24 h post-operatively as the primary outcome...
July 2017: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/28508197/antinociceptive-effect-of-the-agonist-of-5-ht1a-receptors-buspirone-in-the-model-of-abdominal-pain-in-dogs
#15
O A Lyubashina, I I Busygina, S S Panteleev, A D Nozdrachev
We have demonstrated that activation of 5-HT1A receptors with buspirone promotes visceral analgesia in awake dogs. The administration of 0.035 mg/kg (i.m.) of the drug caused depression of viscero-motor (contraction of the abdominal muscles) and pressor (increase in the heart rate) responses to noxious distension of the large intestine. An increase in the dose to 0.07 and 0.14 mg/kg did not enhance the antinociceptive effect of buspirone but triggered basal tachycardia. The obtained results provide evidence of the inhibitory role of 5-HT1A receptors in modulating visceral pain sensitivity and the possibility of an exciting effect of their activation on the cardiovascular system...
March 2017: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/28503726/baroreflex-dysfunction-and-augmented-sympathetic-nerve-responses-during-mental-stress-in-veterans-with-posttraumatic-stress-disorder-ptsd
#16
Jeanie Park, Paul J Marvar, Peizhou Liao, Melanie L Kankam, Seth D Norrholm, Ryan M Downey, S Ashley McCullough, Ngoc-Anh Le, Barbara O Rothbaum
Posttraumatic Stress Disorder (PTSD) is associated with increased cardiovascular (CV) risk. We tested the hypothesis that PTSD patients have augmented sympathetic nervous system (SNS) and hemodynamic reactivity during mental stress, and impaired arterial baroreflex sensitivity (BRS). 14 otherwise healthy Veterans with combat-related PTSD were compared to 14 matched Controls without PTSD.  Muscle sympathetic nerve activity (MSNA), continuous blood pressure (BP), and electrocardiography were measured at baseline, and during two types of mental stress:  combat-related mental stress using virtual reality combat exposure (VRCE); and noncombat related stress using mental arithmetic (MA)...
May 14, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28501796/nitric-oxide-synthase-inhibition-restores-orthostatic-tolerance-in-young-vasovagal-syncope-patients
#17
Julian M Stewart, Richard Sutton, Mira L Kothari, Amanda M Goetz, Paul Visintainer, Marvin Scott Medow
OBJECTIVE: Syncope is sudden transient loss of consciousness and postural tone with spontaneous recovery; the most common form is vasovagal syncope(VVS). We previously demonstrated impaired post-synaptic adrenergic responsiveness in young VVS patientswas reversed by blocking nitric oxide synthase(NOS). We hypothesised that nitric oxide may account for reduced orthostatic tolerance in young recurrent VVS patients. METHODS: We recorded haemodynamics in supine VVS and healthy volunteers (aged 15-27 years), challenged with graded lower body negative pressure (LBNP) (-15, -30, -45 mm Hg each for 5 min, then -60 mm Hg for a maximum of 50 min) with and without NOS inhibitor N(G)-monomethyl-L-arginine acetate(L-NMMA)...
May 13, 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/28501551/contribution-of-stress-and-sex-hormones-to-memory-encoding
#18
Christian J Merz
Distinct stages of the menstrual cycle and the intake of oral contraceptives (OC) affect sex hormone levels, stress responses, and memory processes critically involved in the pathogenesis of mental disorders. To characterize the interaction of sex and stress hormones on memory encoding, 30 men, 30 women in the early follicular phase of the menstrual cycle (FO), 30 women in the luteal phase (LU), and 30 OC women were exposed to either a stress (socially evaluated cold-pressor test) or a control condition prior to memory encoding and immediate recall of neutral, positive, and negative words...
May 6, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28499135/pain-threshold-tolerance-and-intensity-in-adolescents-born-very-preterm-or-with-low-birth-weight
#19
Christ-Jan J L M van Ganzewinkel, Jasper V Been, Inge Verbeek, Tera Boelen van der Loo, Sylvia M van der Pal, Boris W Kramer, Peter Andriessen
BACKGROUND: Data on long-term consequences of neonatal pain is limited. AIM: To assess whether perinatal factors, later pain experience and pain coping strategies are associated with altered pain threshold, pain tolerance and pain intensity in adolescents born preterm. STUDY DESIGN: Observational, longitudinal study (Project on Preterm and SGA-infants, POPS-19). SUBJECTS: We analyzed data of 412 adolescents at the age of 19years, who were born at a gestational age<32weeks or with a birth weight<1500g...
July 2017: Early Human Development
https://www.readbyqxmd.com/read/28489648/clinical-experience-with-iv-angiotensin-ii-administration-a-systematic-review-of-safety
#20
Laurence W Busse, Xueyuan Shelly Wang, Divya M Chalikonda, Kevin W Finkel, Ashish K Khanna, Harold M Szerlip, David Yoo, Sharon L Dana, Lakhmir S Chawla
OBJECTIVE: Angiotensin II is an endogenous hormone with vasopressor and endocrine activities. This is a systematic review of the safety of IV angiotensin II. DATA SOURCES: PubMed, Medline, Scopus, and Cochrane. STUDY SELECTION: Studies in which human subjects received IV angiotensin II were selected whether or not safety was discussed. DATA EXTRACTION: In total, 18,468 studies were screened by two reviewers and one arbiter...
May 9, 2017: Critical Care Medicine
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