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https://www.readbyqxmd.com/read/28526554/the-roles-of-orexins-in-sleep-wake-regulation
#1
REVIEW
Michihiro Mieda
Orexin A and orexin B are hypothalamic neuropeptides initially identified as endogenous ligands for two orphan G-protein coupled receptors (GPCRs). A deficiency of orexin signaling results in the sleep disorder narcolepsy-cataplexy in humans, dogs, and rodents, a sleep disorder characterized by excessive daytime sleepiness and cataplexy. Multiple approaches, including molecular genetic, electrophysiological, pharmacological, and neuroanatomical studies have suggested that orexins play critical roles in the maintenance of wakefulness by regulating the function of monoaminergic and cholinergic neurons that are implicated in the regulation of wakefulness...
May 16, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28526553/hypothalamic-regulation-of-the-sleep-wake-cycle
#2
REVIEW
Daisuke Ono, Akihiro Yamanaka
Sleep is one of the most important physiological functions in mammals. It is regulated by not only homeostatic regulation but also circadian clock. Several neuropeptide-producing neurons located in the hypothalamus are implicated in the regulation of sleep/wakefulness. Among them, orexin/hypocretin-producing neurons (orexin neurons) are a crucial component for maintenance of wakefulness, because lack of orexin function results in narcolepsy, which is a sleep disorder. Recent findings have identified substances that excite or inhibit neural activity of orexin neurons...
May 16, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28522102/retrospective-multicenter-matched-case-control-study-on-the-risk-factors-for-narcolepsy-with-special-focus-on-vaccinations-including-pandemic-influenza-vaccination-and-infections-in-germany
#3
Doris Oberle, Jutta Pavel, Geert Mayer, Peter Geisler, Brigitte Keller-Stanislawski
OBJECTIVE: Studies associate pandemic influenza vaccination with narcolepsy. In Germany, a retrospective, multicenter, matched case-control study was performed to identify risk factors for narcolepsy, particularly regarding vaccinations (seasonal and pandemic influenza vaccination) and infections (seasonal and pandemic influenza) and to quantify the detected risks. METHODS: Patients with excessive daytime sleepiness who had been referred to a sleep center between April 2009 and December 2012 for multiple sleep latency test (MSLT) were eligible...
June 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28522101/cardiovascular-fitness-in-narcolepsy-is-inversely-related-to-sleepiness-and-the-number-of-cataplexy-episodes
#4
Martin Matoulek, Vladimír Tuka, Magdalena Fialová, Soňa Nevšímalová, Karel Šonka
OBJECTIVE: Cardiopulmonary fitness depends on daily energy expenditure or the amount of daily exercise. Patients with narcolepsy spent more time being sleepy or asleep than controls; thus we may speculate that they have a lower quantity and quality of physical activity. The aim of the present study was thus to test the hypothesis that exercise tolerance in narcolepsy negatively depends on sleepiness. PATIENTS AND METHODS: The cross-sectional study included 32 patients with narcolepsy with cataplexy, 10 patients with narcolepsy without cataplexy, and 36 age- and gender-matched control subjects, in whom a symptom-limited exercise stress test with expired gas analysis was performed...
June 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28522097/sleep-spindle-density-in-narcolepsy
#5
Julie Anja Engelhard Christensen, Miki Nikolic, Mathias Hvidtfelt, Birgitte Rahbek Kornum, Poul Jennum
BACKGROUND: Patients with narcolepsy type 1 (NT1) show alterations in sleep stage transitions, rapid-eye-movement (REM) and non-REM sleep due to the loss of hypocretinergic signaling. However, the sleep microstructure has not yet been evaluated in these patients. We aimed to evaluate whether the sleep spindle (SS) density is altered in patients with NT1 compared to controls and patients with narcolepsy type 2 (NT2). METHODS: All-night polysomnographic recordings from 28 NT1 patients, 19 NT2 patients, 20 controls (C) with narcolepsy-like symptoms, but with normal cerebrospinal fluid hypocretin levels and multiple sleep latency tests, and 18 healthy controls (HC) were included...
June 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28522087/mazindol-a-risk-factor-for-pulmonary-arterial-hypertension
#6
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/28522076/sleep-wake-stability-in-narcolepsy-patients-with-normal-low-and-unmeasurable-hypocretin-levels
#7
Mathias Hvidtfelt Hansen, Birgitte Rahbek Kornum, Poul Jennum
OBJECTIVE: To compare diurnal and nocturnal electrophysiological data from narcolepsy patients with undetectable (<20 pg/mL), low (20-110 pg/mL) and normal (>110 pg/mL) cerebrospinal fluid (CSF) hypocretin-1 levels. PATIENTS/METHODS: A total of 109 narcolepsy patients and 37 controls were studied; all had available CSF hypocretin-1 measurements. The sleep laboratory studies were conducted between 2008 and 2014. The study retrospectively examined measurements of sleep stage transitions in diurnal and nocturnal continuous polysomnography...
June 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28511597/understanding-sleep-wake-mechanisms-and-drug-discovery
#8
Ana Clementina Equihua-Benítez, Khalil Guzmán-Vásquez, René Drucker-Colín
Although not discernible at first glance, sleep is a highly active and regulated brain state. Although we spend practically one third of our lifetimes in this stage, its importance is often taken for granted. Sleep loss can lead to disease, error and economic loss. Our understanding of how sleep is achieved has greatly advanced in recent years, and with that, the management of sleep disorders has improved. Nevertheless, there is still room for improvement and recently many new compounds have reached clinical trials with a few being approved for commercial use...
May 17, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28511486/a-review-on-detection-and-treatment-methods-of-sleep-apnea
#9
REVIEW
Rajeswari Jayaraj, Jagannath Mohan, Adalarasu Kanagasabai
This paper presents a review on detection and treatment methods of sleep apnea. Sleep apnea is the most common type of breathing-related sleep disorder. It manifests in a variety of behaviours from teeth grinding to night terrors as involuntary night-time events. The most common sleep disorders are narcolepsy, hypersomnia, sleep talking, sleep walking, and bedwetting. Sleep apnea (somnipathy) is a serious sleep disorder that pauses breathing while sleeping. Breathing pauses occur 30 times or more during sleep and it lasts for few seconds to minutes, when normal breathing starts after this pause...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28507129/nonpeptide-orexin-type-2-receptor-agonist-ameliorates-narcolepsy-cataplexy-symptoms-in-mouse-models
#10
Yoko Irukayama-Tomobe, Yasuhiro Ogawa, Hiromu Tominaga, Yukiko Ishikawa, Naoto Hosokawa, Shinobu Ambai, Yuki Kawabe, Shuntaro Uchida, Ryo Nakajima, Tsuyoshi Saitoh, Takeshi Kanda, Kaspar Vogt, Takeshi Sakurai, Hiroshi Nagase, Masashi Yanagisawa
Narcolepsy-cataplexy is a debilitating disorder of sleep/wakefulness caused by a loss of orexin-producing neurons in the lateroposterior hypothalamus. Genetic or pharmacologic orexin replacement ameliorates symptoms in mouse models of narcolepsy-cataplexy. We have recently discovered a potent, nonpeptide OX2R-selective agonist, YNT-185. This study validates the pharmacological activity of this compound in OX2R-transfected cells and in OX2R-expressing neurons in brain slice preparations. Intraperitoneal, and intracerebroventricular, administration of YNT-185 suppressed cataplexy-like episodes in orexin knockout and orexin neuron-ablated mice, but not in orexin receptor-deficient mice...
May 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28499899/the-wake-promoting-drug-modafinil-prevents-motor-impairment-in-sickness-behavior-induced-by-lps-in-mice-role-for-dopaminergic-d1-receptor
#11
Adriano Zager, Wesley Nogueira Brandão, Rafael Oliveira Margatho, Jean Pierre Peron, Sergio Tufik, Monica Levy Andersen, Birgitte Rahbek Kornum, João Palermo-Neto
The wake-promoting drug Modafinil has been used for many years for treatment of Narcolepsy and Excessive Daytime Sleepiness, due to a dopamine-related psychostimulant action. Recent studies have indicated that Modafinil prevents neuroinflammation in animal models. Thus, the aim of the present study was to evaluate the effect of Modafinil pretreatment in the Lipopolysaccharide (LPS)-induced sickness and depressive-like behaviors. Adult male C57BL/6J mice were pretreated with Vehicle or Modafinil (90mg/Kg) and, 30min later, received a single saline or LPS (2mg/Kg) administration, and were submitted to the open field and elevated plus maze test 2h later...
May 9, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28490912/update-on-the-treatment-of-narcolepsy-clinical-efficacy-of-pitolisant
#12
REVIEW
Michael W Calik
Narcolepsy is a neurological disease that affects 1 in 2,000 individuals and is characterized by excessive daytime sleepiness (EDS). In 60-70% of individuals with narcolepsy, it is also characterized by cataplexy or a sudden loss of muscle tone that is triggered by positive or negative emotions. Narcolepsy decreases the quality of life of the afflicted individuals. Currently used drugs treat EDS alone (modafinil/armodafinil, methylphenidate, and amphetamine), cataplexy alone ("off-label" use of antidepressants), or both EDS and cataplexy (sodium oxybate)...
2017: Nature and Science of Sleep
https://www.readbyqxmd.com/read/28472332/the-spectrum-of-rem-sleep-related-episodes-in-children-with-type-1-narcolepsy
#13
Elena Antelmi, Fabio Pizza, Stefano Vandi, Giulia Neccia, Raffaele Ferri, Oliviero Bruni, Marco Filardi, Gaetano Cantalupo, Rocco Liguori, Giuseppe Plazzi
Type 1 narcolepsy is a central hypersomnia due to the loss of hypocretin-producing neurons and characterized by cataplexy, excessive daytime sleepiness, sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. In children, close to the disease onset, type 1 narcolepsy has peculiar clinical features with severe cataplexy and a complex admixture of movement disorders occurring while awake. Motor dyscontrol during sleep has never been systematically investigated. Suspecting that abnormal motor control might affect also sleep, we systematically analysed motor events recorded by means of video polysomnography in 40 children with type 1 narcolepsy (20 females; mean age 11...
May 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28471950/comparison-of-sleep-latency-and-number-of-soremps-in-the-home-and-hospital-with-a-modified-multiple-sleep-latency-test-a-randomized-crossover-study
#14
Kornelia K Beiske, Trond Sand, Eyvind Rugland, Knut Stavem
PURPOSE: Comparison of mean sleep latencies and number of sleep-onset rapid eye movement periods (SOREMPs) between modified multiple sleep latency test (MSLT) performed in the unattended home and in-hospital laboratory setting. METHODS: A randomized crossover single-blinded design. Thirty-four subjects referred to MSLT for suspected hypersomnia or narcolepsy were included. Participants were randomized to perform modified MSLT in the unattended home or in the hospital first...
May 2017: Journal of Clinical Neurophysiology: Official Publication of the American Electroencephalographic Society
https://www.readbyqxmd.com/read/28460656/gamma-hydroxybutyrate-ghb-an-unusual-cause-of-high-anion-gap-metabolic-acidosis
#15
Laurence Carlier, Vincent Van Belleghem, Kathleen Croes, Frederik Hooft, Matthias Desmet, Olivier Heylen, Stijn Lambrecht, Stefaan Carlier
The causes of high anion gap metabolic acidosis (HAGMA) are well described in the literature. However, sometimes more frequent causes of HAGMA cannot explain its occurrence. In the case of HAGMA and severe neurological depression in the absence of other causes of HAGMA, clinicians should consider an intoxication with gamma-hydroxybutyrate (GHB) as a possible cause. GHB is endogenous to the mammalian central nervous system (CNS). Synthetic GHB was initially used as an anesthetic but is now only licensed for medical use in a limited number of indications such as the treatment of narcolepsy...
May 2, 2017: CJEM
https://www.readbyqxmd.com/read/28460015/rare-missense-mutations-in-p2ry11-in-narcolepsy-with-cataplexy
#16
Matilda Degn, Yves Dauvilliers, Karin Dreisig, Régis Lopez, Corinne Pfister, Sylvain Pradervand, Birgitte Rahbek Kornum, Mehdi Tafti
The sleep disorder narcolepsy with cataplexy is characterized by a highly specific loss of hypocretin (orexin) neurons, leading to the hypothesis that the condition is caused by an immune or autoimmune mechanism. All genetic variants associated with narcolepsy are immune-related. Among these are single nucleotide polymorphisms in the P2RY11-EIF3G locus. It is unknown how these genetic variants affect narcolepsy pathogenesis and whether the effect is directly related to P2Y11 signalling or EIF3G function. Exome sequencing in 18 families with at least two affected narcolepsy with cataplexy subjects revealed non-synonymous mutations in the second exon of P2RY11 in two families, and P2RY11 re-sequencing in 250 non-familial cases and 135 healthy control subjects revealed further six different non-synonymous mutations in the second exon of P2RY11 in seven patients...
April 27, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28449905/sleep-wake-patterns-non-rapid-eye-movement-and-rapid-eye-movement-sleep-cycles-in-teenage-narcolepsy
#17
Xing Xu, Huijuan Wu, Jianhua Zhuang, Kun Chen, Bei Huang, Zhengqing Zhao, Zhongxin Zhao
BACKGROUND: To further characterize sleep disorders associated with narcolepsy, we assessed the sleep-wake patterns, rapid eye movement (REM), and non-REM (NREM) sleep cycles in Chinese teenagers with narcolepsy. METHODS: A total of 14 Chinese type 1 narcoleptic patients (13.4 ± 2.6 years of age) and 14 healthy age- and sex-matched control subjects (13.6 ± 1.8 years of age) were recruited. Ambulatory 24-h polysomnography was recorded for two days, with test subjects adapting to the instruments on day one and the study data collection performed on day two...
May 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28449899/comorbidity-of-narcolepsy-with-cataplexy-and-transverse-myelitis-a%C3%A2-common-autoimmune-background-a-case-report
#18
Rosa Peraita-Adrados, Julia Romero-Martínez, Juan A Guzmán-De Villoria, Laura Lillo-Triguero, María Luisa Martínez-Ginés
No abstract text is available yet for this article.
May 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28449892/medical-comorbidity-in-narcolepsy-findings-from-the-burden-of-narcolepsy-disease-bond-study
#19
J Black, N L Reaven, S E Funk, K McGaughey, M M Ohayon, C Guilleminault, C Ruoff
OBJECTIVE/BACKGROUND: The objective of this study was to evaluate medical comorbidity patterns in patients with a narcolepsy diagnosis in the United States. PATIENTS/METHODS: This was a retrospective medical claims data analysis. Truven Health Analytics MarketScan® Research Databases were accessed to identify individuals ≥18 years of age with ≥1 diagnosis code for narcolepsy (International Classification of Diseases (ICD)-9, 347.0, 347.00, 347.01, 347.1, 347...
May 2017: Sleep Medicine
https://www.readbyqxmd.com/read/28449891/the-european-medicines-agency-review-of-pitolisant-for-treatment-of-narcolepsy-summary-of-the-scientific-assessment-by-the-committee-for-medicinal-products-for-human-use
#20
Marta Kollb-Sielecka, Pierre Demolis, Joseph Emmerich, Greg Markey, Tomas Salmonson, Manuel Haas
On 31 March 2016, the European Commission issued a decision for a marketing authorisation valid throughout the European Union (EU) for pitolisant (Wakix) for the treatment of narcolepsy with or without cataplexy in adults. Pitolisant is an antagonist/inverse agonist of the human histamine H3 receptor. The dose should be selected using an up-titration scheme depending on individual patient response and tolerance and should not exceed 36 mg/day. The main evidence of efficacy of pitolisant was based on two Phase III clinical trials...
May 2017: Sleep Medicine
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