Alcoholism ; metabolism ; pathology ; Animals ; Humans ; Orexins ; metabolism

OBJECTIVE: To compare the effect on post-stroke insomnia between the repetitive transcranial acupuncture stimulation (rTAS) and the conventional western medication in the patients and to explore the mechanism. METHODS: Ninety patients of post-stroke insomnia were randomized into a rTAS group, a medication group and a placebo group, 30 cases in each one. In the rTAS group, patients were intervened by rTAS. The acupoints were Baihui (GV 20), Ningshen (Extra), emotion area, Wangu (GB 12), Taiyang (EX-HN 5), Neiguan (PC 6), Shenmen (HT 7), Sanyinjiao (SP 6), Zhaohai (KI 6), Zusanli (ST 36) and Taichong (LR 3). Fast twist with small amplitude was used at Baihui (GV 20) and emotion area for 2-3 min, 200-300 r/min, once 15 min. Electroacupuncture (EA) was applied at Baihui (GV 20) and Ningshen (Extra), bilateral Wangu (GB 12), Sanyinjiao (SP 6) and Zhaohai (KI 6) on the same side, 10 Hz, 0.5-1 mA. The treatment was given for 40 min in the rTAS group, once a day. Diazepam was prescribed orally in the medication group before sleep, 2.5 mg a day. Starch capsule was used in the placebo group before sleep, once a day. All the treatment was given for continuous 1 month. The level of serum orexin A was observed before and after treatment. The effects were compared. The recurrence rate was recorded 3 months after treatment. RESULTS: The total effective rates in the rTAS group and the medication group were 86.7% (26/30) and 90.0% (27/30) repectively after treatment, which were better than 20.0% (6/30) in the placebo group (both <0.01). After treatment, the levels of serum orexin A in the rTAS group and the medication group were lower than those before treatment (both <0.01), which were lower than that in the placebo group after treatment (both <0.01), without statistical significance between the rTAS group and the medication group after treatment (>0.05). The total effective rates in the rTAS group and the medication group were 86.7% (26/30) and 86.7% (26/30) at follow-up repectively, which were better than 16.7% (5/30) in the placebo group (both <0.01). CONCLUSION The rTAS is safe and effective for post-stroke insomnia, which is similar to oral medication of diazepam. The decreasing serum orexin A may be one of the mechanisms.
Acupuncture Therapy ; Humans ; Orexins ; Sleep Initiation and Maintenance Disorders ; therapy ; Stroke

Narcolepsy with cataplexy (NC) is associated with hypocretin deficiency, and is thought to be an autoimmunity condition. The mean age at onset is estimated to be in the early 20s. Recent papers have addressed the response to immunotherapies in NC, with challenging results. We report a case of late-onset NC in a patient who did not benefit from early intravenous high-dose immunoglobulin (IVIg) therapy. This is the first reported attempt at using IVIg to treat an NC patient in Korea.
Autoimmunity ; Cataplexy ; Humans ; Immunoglobulins ; Immunoglobulins, Intravenous ; Immunotherapy ; Intracellular Signaling Peptides and Proteins ; Korea ; Narcolepsy ; Neuropeptides ; Orexins

Childhood narcolepsy is one of the underdiagnosed diseases even the first symptoms often appear in childhood. Making diagnosis through history taking is not always easy because the symptoms of childhood narcolepsy are different from those of adulthood. Diagnostic laboratory tests such as sleep studies, tests for human leukocyte antigens, cerebrospinal fluid hypocretin measurement should be considered when the child has excessive daytime sleepiness without cataplexy. Treatment approach should be start as early as possible to avoid secondary academic, emotional difficulties. Both pharmacological and non-pharmacological management, and close cooperation between parents and school teachers should be maintained. In the near future, childhood narcolepsy can be a key to understand the pathogenesis of narcolepsy.
Cataplexy ; Child ; HLA Antigens ; Humans ; Intracellular Signaling Peptides and Proteins ; Narcolepsy ; Neuropeptides ; Parents ; Orexins

The cytoprotective enzyme heme oxygenase-1 (HO-1) influences endothelial cell survival, proliferation, inflammatory response, and angiogenesis in response to various angiogenic stimuli. In this study, we investigate the involvement of HO-1 in the angiogenic activity of orexin-A. We showed that orexin-A stimulates expression and activity of HO-1 in human umbilical vein endothelial cells (HUVECs). Furthermore, we showed that inhibition of HO-1 by tin (Sn) protoporphryin-IX (SnPP) reduced orexin-A-induced angiogenesis in vivo and ex vivo. Orexin-A-stimulated endothelial tube formation and chemotactic activity were also blocked in SnPP-treated vascular endothelial cells. Orexin-A treatment increased the expression of nuclear factor erythroid-derived 2 related factor 2 (Nrf2), and antioxidant response element (ARE) luciferase activity, leading to induction of HO-1. Collectively, these findings indicate that HO-1 plays a role as an important mediator of orexin-A-induced angiogenesis, and provide new possibilities for therapeutic approaches in pathophysiological conditions associated with angiogenesis.
Antioxidant Response Elements ; Endothelial Cells* ; Heme Oxygenase-1* ; Human Umbilical Vein Endothelial Cells ; Luciferases ; Tin ; Orexins

The neuropeptide orexin is widely distributed in the nervous system. Previous studies showed that orexin is involved in the feeding behavior regulation by binding to its receptor 1 (OX1R) and receptor 2 (OX2R) to activate the downstream signaling pathway. Recent studies have demonstrated that the system of orexin and its receptors are also involved in important physiological processes such as sleep-wake, learning and memory, and pathological processes of various neurological diseases. In this review, we summarized the research progress on the function of the orexin and its receptor system in physiological and pathological processes, and revealed the correlation between orexin and nervous system diseases, in order to provide the theoretical guidance for the diagnosis and treatment of the related diseases in the future.
Humans ; Nervous System Diseases ; physiopathology ; Orexin Receptors ; physiology ; Orexins ; physiology ; Signal Transduction

BACKGROUND: The purpose of this study was to investigate the differences of cerebral glucose metabolism between narcoleptic patients and normal controls. METHODS: We enrolled 24 patients with narcolepsy who underwent night polysomnography and multiple sleep latency tests to confirm the narcolepsy. 18F-fluorodeoxy glucose positron emission tomography scan was performed in all narcoleptic patients and 24 normal age-sex matched controls. To compare the cerebral glucose metabolism between the two groups, statistical parametric mapping (SPM99) was used. RESULTS: Patients with narcolepsy showed significant decreases of cerebral glucose metabolism in the bilateral rectal and subcallosal gyri, right superior frontal gyrus, right medial frontal gyrus, bilateral precuneus, right inferior parietal lobule, and left supramarginal gyrus of the parietal lobe at the uncorrected P<0.001. The bilateral posterior hypothalami and mediodorsal thalamic nuclei showed glucose hypometabolism at the level of corrected P<0.05 with small volume correction. CONCLUSIONS: This study showed cerebral glucose hypometabolism of hypothalamus-thalamus-orbitofrontal pathways in narcoleptic brains. The distribution of abnormal glucose metabolism is concordant to the cerebral pathways of the hypocretin system.
Brain ; Glucose* ; Humans ; Hypothalamus ; Metabolism* ; Narcolepsy* ; Parietal Lobe ; Polysomnography ; Positron-Emission Tomography ; Rabeprazole ; Thalamic Nuclei ; Thalamus ; Orexins

OBJECTIVES: Narcolepsy is a sleep disorder, characterized by excessive daytime sleepiness, cataplexy, sleep paralysis and hypnagogic hallucination. Among these symptoms, cataplexy is one of the most pathognomonic symptoms in narcolepsy. This study was designed to investigate the clinical features, frequency of DQB1*0602 and CSF hypocretin levels in Korean narcoleptics with cataplexy to compare with those who have not cataplexy. METHODS: From August 2003 to July 2005, we selected 72 patients who have narcolepsy confirmed by nocturnal polysomnography and multiple sleep latency test (MSLT) as well as their history and clinical symptoms at Sleep Disorders Clinic of St. Vincent's Hospital, Catholic University of Korea. Patients were divided into 56 cataplexy-positive group (narcolepsy with cataplexy group) and 12 cataplexy-negative group (narcolepsy without cataplexy group). HLA typing was done in all patients for the presence of DQB1*0602, and patients received spinal tapping to measure the level of CSF hypocretin. Clinical variables were examined by semi-structured interview for narcolepsy patients. RESULTS: 1) In cataplexy-positive group, compared with cataplexy-negative group, the frequency of HLA-DQB1*0602 was found to be significantly increased (50 subjects, 89.3% vs. 8 subjects, 50.0%)(p=0.000). 2) In 48 out of 56 cataplexy-positive patients (85.7%), hypocretin levels were decreased (< or =110 pg/ml) or were below the detection limit of assay (<40 pg/ml). However, only 6 out of 16 cataplexy-negative patients (37.5%) exhibited decreased hyopcretin level. The difference between two groups were statistically significant (p=0.000). 3) Cataplexy-positive group, compared to cataplexy-negative group, reported more frequent hypnagogic hallucinations (36 subjects, 64.3% vs. 4 subjects, 25.0%)(p=0.005). However, there were no significant differences in frequency or severity of daytime sleepiness, sleep paralysis and demographic data. 4. In nocturnal polysomnography and MSLT findings, there were no significant differences in all sleep parameters between two groups. CONCLUSION: Higher frequency of HLA-DQB1*0602, and lower hypocretin levels in cataplexy-positive groups than catapelxy-negatives suggest that narcoleptics with cataplexy might be a etiologically different disease entity from narcoleptics without cataplexy. Additionally, Current criteria prevail for the diagnosis of narcolepsy need to be reclassified according to the presence of cataplexy or not.
Cataplexy* ; Diagnosis ; Hallucinations ; Histocompatibility Testing ; Humans ; Korea ; Limit of Detection ; Narcolepsy* ; Polysomnography ; Sleep Wake Disorders ; Sleep Paralysis ; Spinal Puncture ; Orexins

Although bipolar disorder is highly heritable, the identification of specific genetic variations is limited because of the complex traits underlying the disorder. We performed a genome-wide association study of bipolar disorder using a subphenotype that shows hypersomnia symptom during a major depressive episode. We investigated a total of 2,191 cases, 1,434 controls, and 703,012 single nucleotide polymorphisms (SNPs) in the merged samples obtained from the Translational Genomics Institute and the Genetic Association Information Network. The gene emerging as the most significant by statistical analysis was rs1553441 (odds ratio=0.4093; p=1.20x10-5; Permuted p=6.0x10-6). However, the 5x0-8 threshold for statistical significance required in a genome-wide association study was not achieved. The functional enrichment pathway analysis showed significant enrichments in the adhesion, development-related, synaptic transmission-related, and cell recognition-related pathways. For further evaluation, each gene of the enriched pathways was reviewed and matched with genes that were suggested to be associated with psychiatric disorders by previous genetic studies. We found that the cadherin 13 and hypocretin (orexin) receptor 2 genes may be involved in the hypersomnia symptom during a major depressive episode of bipolar disorder.
Bipolar Disorder* ; Disorders of Excessive Somnolence* ; Genetic Variation ; Genome-Wide Association Study ; Genomics ; Information Services ; Polymorphism, Single Nucleotide ; Orexins

OBJECTIVECurrently people regard polysomnography (PSG) monitoring as the golden standard for diagnosis of obstructive sleep apnea-hypopnea syndrome (OSAHS) in children. However, due to the high cost, time and manpower consuming, PSG is not applicable to epidemiological investigation and clinical screening, especially not suitable for child patients and remote hospitals in Xinjiang. Therefore, it is of important clinical significance to find out a simple method (e.g. a kind of serum index) to primarily screen out suspicious patients for early diagnosis and treatment. The present study was conducted to assess the clinical usefulness of the measurement of orexin-A concentration in serum as a diagnostic predictor to screen patients with OSAHS in children.

METHODSSerum orexin-A concentration was measured with enzyme immunoassay (EIA) kit in 60 patient with snoring before performing polysomnography (PSG). Subsequently all the subjects underwent PSG test. Forty subjects were diagnosed as having OSAHS, and twenty subjects had no OSAHS. These 20 non-OSAHS subjects served as controls. Compared with the PSG results the clinical usefulness of the measurement of orexin-A concentration in serum was assessed as a diagnostic predictor to screen patients with OSAHS. Correlation between orexin-A levels and apnea hypoventilation index (AHI), micro-arousal index (MAI) and lowest SaO2 (LSaO2) were analyzed.

RESULTSThe serum orexin-A levels in the OSAHS group [(0.49 +/- 0.10) microg/L] was significantly higher than that of the control group [(0.28 +/- 0.11) microg/L, P < 0.01]. If a patient's level of orexin-A was higher than 0.36 microg/L, the patient more likely to have OSAHS. The sensitivity rate was 85.0% and the specificity was 80.0%. Serum orexin-A levels in children with OSAHS correlated positively with the AHI (r = 0.427, P < 0.05) and MAI (r = 0.468, P < 0.05), but correlated negatively with the LSaO2 (r = -0.527, P < 0.01) and the mean oxygen saturation (MSaO2) (r = -0.541, P < 0.01), not correlated significantly with the BMI (r = -0.212, P > 0.05). The serum orexin-A levels in the OSAHS children after who under went tonsillectomy and adenoidectomy significantly decreased (P < 0.05) 3 months after surgery as compared with pre-operation level.

CONCLUSIONThese findings suggest that the serum level of orexin-A could be used as a predictor in screening for OSAHS children and a biological marker of the severity of OSAHS children.

Case-Control Studies ; Child ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; blood ; Male ; Neuropeptides ; blood ; Orexins ; Sleep Apnea, Obstructive ; blood ; diagnosis