A randomized placebo-controlled double-blind study of dexmedetomidine on postoperative sleep quality in patients with endoscopic sinus surgery.

BACKGROUND: Postoperative sleep disorder is common and may cause aggravated postoperative pain, delirium, and poor prognosis. We accessed the effect of intraoperative intravenous dexmedetomidine on postoperative sleep quality in patients with endoscopic sinus surgery.  METHODS: This single-center, double-blind, placebo-controlled randomized clinical trial enrolled a total of 110 participants aged 18 years to 65 years who were scheduled to receive endoscopic sinus surgery. Placebo (normal saline) or dexmedetomidine infusion (load dose 0.5 µg kg-1 over 10 min, followed by maintenance dose 0.2 ug kg-1 h-1) during surgery. The primary outcome was postoperative sleep quality. Secondary outcomes were postoperative Ramsay sedation scores, Visual Analog Scale (VAS) scores, serum cortisol, 5-hydroxytryptamine (5-HT) and hypocretin, delirium, and postoperative nausea and vomiting (PONV). RESULTS: Among enrolled 110 patients, 55 were randomized to administer intraoperative dexmedetomidine and placebo. In total, 14 patients (7 in each group) were excluded because of protocol deviations, and 96 patients (48 in each group) were included in the per-protocol analysis. The dexmedetomidine group had a significantly higher sleep efficiency index(SEI) (66.85[3.00] vs 65.38[3.58]), the ratio of rapid eye movement sleep to total sleep(REM)(13.63[1.45] vs 12.38[2.11]) and lower arousal index (AI) (7.20[1.00] vs 8.07[1.29]), higher Ramsay sedation score at post-operation 1 h, 12 h point, lower VAS scores at post-operation 1 h, 12 h, 24 h point, lower cortisol, higher 5-HT and hypocretin in serum than the placebo group. CONCLUSION: In this randomized clinical trial, dexmedetomidine can improve the sleep quality of patients undergoing endoscopic sinus surgery. These results suggest that this therapy may be a viable strategy to enhance postoperative sleep quality in patients with endoscopic sinus surgery. TRIAL REGISTRATION: The study was approved by the Bethune International Peace Hospital Ethics Committee (2021-KY-129) and registered in the Chinese Clinical Trial Registry ( ChiCTR2100051598 , 28/09/2021).

Basal blood concentrations of some orexigenic and anorexigenic hormones in obese and nonobese individuals according to blood groups.

OBJECTIVE: Obesity is a serious public health problem associated with excessive food intake. Regulation of food intake in highly organized organisms is under the control of a large number of orexigenic and anorexigenic molecules. Therefore, the main purpose of this study has been to determine the relationship between obesity and some of the circulating orexigenic and anorexigenic peptides that have a role in appetite control and to determine whether the concentrations of these molecules differ according to blood groups. PATIENTS AND METHODS: The study included 400 individuals of whom 100 were obese women, 100 obese men, 100 healthy men and 100 healthy women. Obese women and men were divided into 4 groups, according to their blood groups. In the control group, healthy women and healthy men were similarly divided into 4 blood groups. Each blood group within the groups, therefore, had 25 participants. RESULTS: When leptin, nesfatin-1, obestatin and neuropeptide-Y, ghrelin and galanin levels of the control group and obese participants were compared, regardless of blood groups, leptin, nesfatin-1, obestatin and neuropeptide-Y were significantly higher, whereas only the ghrelin levels were significantly lower in obese patients. When the amounts of these hormones were measured according to gender, the situation was similar. When leptin, nesfatin-1, obestatin and neuropeptide-Y values of the control and obese participants' blood groups were compared with each other; these hormones were high in all blood groups; however, leptin levels in A blood group, nesfatin-1 levels in AB and O blood group, obestatin levels in AB blood group, neuropeptide-Y levels in A, B, AB blood groups were significantly higher. When the ghrelin levels of the blood groups in the control group and obese participants were compared, it was only significantly lower in the AB blood group. The ghrelin levels in the other blood groups of the obese individuals were again low, but not significantly so. When the distribution of hormones according to gender was evaluated, a situation parallel to the above results was recorded. CONCLUSIONS: Leptin, nesfatin-1, obestatin and neuropeptide-Y and galanin levels of obese individuals were significantly higher than the control values, whereas the ghrelin values were significantly lower regardless of blood groups. Also, these hormones in blood partly varied with ABO blood groups. These different concentrations of hormones in ABO blood groups might be related with stimulation or suppression of appetite in human. However, further studies in other ethnic groups are needed to confirm these results.

Association of fasting orexin-A levels with energy intake at breakfast and subsequent snack in Chilean adolescents.

Orexin-A, a hormone secreted by orexin neurons, is involved in caloric-intake regulation. Current understanding is based primarily on animal studies. Studies of orexin in humans are scarce, and to our knowledge there are no prior studies in adolescents. We studied fasting Orexin-A levels related to energy intake at breakfast and a subsequent snack in adolescents (n = 668) from a longitudinal study in Chile. Body-Mass Index (BMI), components of the metabolic syndrome and fasting blood levels of leptin, insulin, ghrelin, and orexin-A were measured. Energy intake was calculated based on food weights before and after the standardized breakfast and subsequent snack. High energy intake was defined as ≥ 75th percentile. We assessed the relationship between orexin-A and high energy intake, adjusting for confounders. Higher orexin levels were associated with high breakfast energy intake (OR: 1.21; 95%CI: 0.98-1.49). Conversely, those with higher orexin levels showed a non-significant trend for lower odds of high energy intake for the snack (OR: 0.87; 95%CI: 0.70-1.07). There was a significant interaction between high breakfast energy intake and orexin levels. Those who ate more calories at breakfast displayed a lower inhibitory effect of orexin on eating at the snack (p < 0.05). There was no significant interaction between weight status and orexin. In conclusion, orexin-A levels were associated with breakfast energy intake and inversely related with subsequent snack energy intake in participants whose caloric intake at breakfast was within the normal range. Based on these findings, it appears that the association of orexin-A with energy intake depends on eating behavior.

Investigation of serum levels of orexin-A, transforming growth factor ß, and leptin in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disease affecting various inflammatory and nutritional parameters. Therefore, this study aimed to investigate the relationship between the Body Mass Index (BMI) of MS patients and the serum levels of leptin, orexin-A, and Transforming Growth Factor ß (TGF-ß). METHODS: This cross-sectional study included 25 patients suffering from MS and 40 healthy individuals as the case and control groups, respectively. The serum levels of leptin, orexin-A, and TGF-ß were assessed in the participants using the Enzyme-Linked Immunosorbent Assay methods. Moreover, data were analyzed using the descriptive statistical indices, t-test, chi-square test, and linear regression test. RESULTS: According to our results, the participants' mean age was 38.04 ± 7.53 and 40.23 ± 5.88 in the case and control groups, respectively. Also, the groups were not significantly different in gender, age, alcohol consumption, and smoking (p > 0.05). It was found that the mean serum levels of orexin-A and TGF-ß were significantly lower in the MS patients compared to the control group, while the mean serum leptin levels were significantly higher (42.8 vs. 18.9 ng/ml, p < 0.001). Moreover, there was no significant relationship between the BMI of the MS patients and their serum levels of orexin-A, TGF-ß, and leptin (p > 0.05). CONCLUSIONS: In conclusion, we found significantly lower levels of orexin-A and TGF-ß and a significantly higher level of leptin in the MS patients compared to the control group. In addition, there was no significant relationship between the BMI and the serum levels of orexin-A, TGF-ß, and leptin in MS patients.

Changes of Hypocretin (Orexin) System in Schizophrenia: From Plasma to Brain.

Hypocretin (also called orexin) regulates various functions, such as sleep-wake rhythms, attention, cognition, and energy balance, which show significant changes in schizophrenia (SCZ). We aimed to identify alterations in the hypocretin system in SCZ patients. We measured plasma hypocretin-1 levels in SCZ patients and healthy controls and found significantly decreased plasma hypocretin-1 levels in SCZ patients, which was mainly due to a significant decrease in female SCZ patients compared with female controls. In addition, we measured postmortem hypothalamic hypocretin-1-immunoreactivity (ir), ventricular cerebrospinal fluid (CSF) hypocretin-1 levels, and hypocretin receptor (Hcrt-R) mRNA expression in the superior frontal gyrus (SFG) in SCZ patients and controls We observed a significant decrease in the amount of hypothalamic hypocretin-1 ir in SCZ patients, which was due to decreased amounts in female but not male patients. Moreover, Hcrt-R2 mRNA in the SFG was decreased in female SCZ patients compared with female controls, while male SCZ patients showed a trend of increased Hcrt-R1 mRNA and Hcrt-R2 mRNA expression compared with male controls. We conclude that central hypocretin neurotransmission is decreased in SCZ patients, especially female patients, and this is reflected in the plasma.

Orexin a levels of adolescents with major depressive disorder.

OBJECTIVE: This study examines orexin A levels in adolescents with major depressive disorder (MDD). METHODS: Serum orexin A levels of adolescents with MDD (n = 40) were compared to healthy controls (n = 38) using ANCOVA test. In addition, the relationship between orexin A levels and MDD symptom severity (i.e., child depression inventory) was investigated in the MDD group using correlation and linear regression analyses. RESULTS: Orexin A levels of the subjects with MDD were similar to controls while controlling for age, gender, body mass index, and anxiety levels of the subjects. In addition, correlation and regression analyses did not reveal any relationship between orexin A and MDD symptoms. DISCUSSION: Adolescent MDD is not associated with orexin A according to the findings of this study. Future studies considering the effect of stress on this relationship would improve our understanding of this issue.Key PointsAdult studies exploring the relationship between orexin A and major depressive disorder reported contradictory findings.This study showed no relationship between serum orexin A levels and depressive symptom severity among adolescents with major depressive disorder.Orexin A levels of the subjects with major depressive disorder are not significantly different from healthy adolescents.

Differences in serum orexin-A levels between the acute and subacute withdrawal phases in individuals who use methamphetamine.

Orexin has been suggested to play a role in regulating the reward circuits and enhancing drug-seeking behaviors; however, its role in methamphetamine (METH) addiction remains unclear. We previously found that blood orexin-A levels are upregulated in individuals with recent METH exposure. Whether the levels would be altered following withdrawal is unknown. In this study, we compared the levels of serum orexin-A in individuals who use METH between the acute withdrawal (AW) phase and the subacute withdrawal (SAW) phase at baseline (T1) and examined the alterations in these levels after 2 weeks of abstinence (T2). In total, 60 participants (51 men and 9 women) were enrolled in the study; 20 participants with METH-positive urine test results were included in the AW group, and 40 participants with METH-negative urine test results who had self-reportedly last taken METH within the preceding 1-2 months were included in the SAW group. Serum orexin-A levels were measured using enzyme-linked immunosorbent assay. No significant differences in orexin-A levels were observed between the AW and SAW groups at baseline (p = .06). After 2 additional weeks of abstinence, the levels decreased significantly in the SAW group (0.58 ± 0.13 ng/mL) but not in the AW group (0.50 ± 0.14 ng/mL, p = .004). Our results demonstrated that orexin-A levels might decrease after a longer period of METH withdrawal, indicating that the orexin system is dysregulated in the addictive process of METH. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Brief Report: Relationship Between Cotinine Levels and Peripheral Endogenous Concentrations of Oxytocin, ß-Endorphin, and Orexin in Individuals With Both Alcohol and Nicotine Use Disorders.

BACKGROUND AND OBJECTIVES: In this secondary analysis of a pilot clinical trial with individuals with alcohol and nicotine use disorders, we investigate the relationship between serum concentrations of oxytocin, ß-endorphin, melatonin, α-melanocyte-stimulating hormone, substance P, and orexin, with objective biomarkers (salivary cotinine and serum γ-glutamyl transferase [GGT]) as well as with self-reported smoking and alcohol drinking. METHODS: Biomarkers for a total of N = 19 participants were analyzed using multiplexed, competitive format immune-assay (peptides) and enzyme competitive immunoassay (saliva). A regression analysis using Pearson's correlation coefficient was utilized to determine correlations. We controlled for multiple comparisons, checked for collinearities, and ran two-sided statistical tests. RESULTS: We found significant positive correlations for cotinine and oxytocin (P = .002), ß-endorphin (P = .008), and orexin (P < .001), but not for either GGT or self-reported smoking or alcohol drinking. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: These preliminary results suggest a relationship between cotinine and oxytocin, ß-endorphin, and orexin, which opens up new potential hypotheses on the potential role of these endocrine pathways in tobacco smokers. (Am J Addict 2021;30:88-91).

Non-selective orexin-receptor antagonist attenuates stress-re-stress-induced core PTSD-like symptoms in rats: Behavioural and neurochemical analyses.

Post-traumatic stress disorder (PTSD) is a psychological disorder affecting many around the world. Growing evidence suggests that orexin-A is involved in the pathophysiology of depression and panic anxiety disorder. However, the role of orexin-A in PTSD remains unclear. Therefore, pharmacological manipulation of orexin-A can be a potential approach for the treatment of PTSD. Male Wistar rats were subjected to stress re-stress (SRS) by restraining them for 2 h followed by foot shock (FS) and halothane exposure on day-2 (D-2). Then the rats were weekly exposed to FS as re-stress cue . Suvorexant, an orexin antagonist (10, 20 and 30 mg/kg p.o.) and paroxetine (10 mg/kg p.o.) were administered from D-8 to D-32. Plasma and cerebrospinal fluid (CSF) were collected for corticosterone and orexin-A measurement. The analysis of serotonin and corticotropin-releasing factor receptor-1 (CRF-R1) were performed in the amygdalar tissue. SRS-induced PTSD-like symptoms like fear response, anxiety-like behaviour and hypocorticosteronism were attenuated by suvorexant and paroxetine. Interestingly, SRS exposed rats showed activation of orexin-A and serotonergic systems, which were also attenuated by suvorexant. Additionally, suvorexant ameliorated the extrahypothalamic induced upregulation of CRH-R1 in SRS-exposed rats. Therefore, orexin-A may be considered as a neurochemical-marker for PTSD and suvorexant alleviated PTSD-like symptoms through modulating orexinergic, serotonergic and neuroendocrine systems.

Increased plasma orexin-A concentrations are associated with the non-motor symptoms in Parkinson's disease patients.

BACKGROUND: Orexin, a neuropeptide primarily secreted by neurons in the lateral hypothalamus, has been implicated in Parkinson's disease (PD). Studies on the relationship between plasma orexin-A levels and PD are rare. OBJECTIVES: This study aimed to assess levels of plasma orexin-A in the progression of PD and to evaluate the correlation between orexin-A levels and non-motor symptoms. METHODS: Enzyme-linked immunosorbent assay was used to determine plasma orexin-A levels in 117 healthy controls and 121 PD patients, including those with early (n = 68), medium (n = 40) and advanced (n = 13) stages of the disease. Evaluation of motor symptoms and non-motor symptoms in PD patients, such as sleep disorders, cognitive dysfunction, neuropsychiatric symptoms, autonomic nervous dysfunction, hyposmia and PD-related pain, were assessed by the associated scales. RESULTS: Plasma orexin-A levels were significantly higher in PD patients compared to healthy controls. Orexin-A levels were elevated in early-stage and medium-stage PD compared to healthy controls, but were decreased in advanced-stage PD. Orexin-A levels were negatively correlated with the Unified Parkinson's Disease Rating Scale Part III scores, disease duration, and dopamine receptor agonist doses, and were positively correlated with the Pittsburgh Sleep Quality Index, REM-sleep Behavior Disorder Questionnaire, 14-item Hamilton Anxiety Scale, Mini-Mental State Examination, and Non-motor Symptom Scale items 22-24 scores. CONCLUSIONS: We found for the first time that plasma orexin-A levels were increased in early-stage and medium-stage PD and were decreased in advanced-stage PD. Furthermore, orexin-A levels were correlated with the non-motor symptoms of insomnia, REM-sleep behavior disorder, anxiety, cognitive dysfunction, and renal dysfunction.

Influence of light/dark cycle and orexins on breathing control in green iguanas (Iguana iguana).

Light/dark cycle affects the physiology of vertebrates and hypothalamic orexin neurons (ORX) are involved in this function. The breathing pattern of the green iguana changes from continuous to episodic across the light/dark phases. Since the stimulatory actions of ORX on breathing are most important during arousal, we hypothesized that ORX regulates changes of breathing pattern in iguanas. Thus, we: (1) Localized ORX neurons with immunohistochemistry; (2) Quantified cyclic changes in plasma orexin-A levels by ELISA; (3) Compared breathing pattern at rest and during hypoxia and hypercarbia; (4) Evaluated the participation of the ORX receptors in ventilation with intracerebroventricular microinjections of ORX antagonists during light and dark phases. We show that the ORX neurons of I. iguana are located in the periventricular hypothalamic nucleus. Orexin-A peaks during the light/active phase and breathing parallels these cyclic changes: ventilation is higher during the light phase than during the dark phase. However, inactivation of ORX-receptors does not affect the breathing pattern. Iguanas increase ventilation during hypoxia only during the light phase. Conversely, CO2 promotes post-hypercarbic hyperpnea during both phases. We conclude that ORXs potentiate the post-hypercarbic (but not the hypoxic)-drive to breathe and are not involved in light/dark changes in the breathing pattern.

Comparison of endocannabinoids levels, FAAH gene polymorphisms, and appetite regulatory substances in women with and without binge eating disorder: a cross- sectional study.

Binge eating disorder (BED) is known as the most common eating disorder with both psychosocial and biological factors involved. In this regard, there is a need to recognize probable disturbances in substances involved in food intake regulation in BED. In this study, we hypothesized that the levels of endocannabinoids, fatty acid amid hydrolase (FAAH) gene polymorphisms, and appetite regulatory substances are different in overweight and obese women with and without BED. A Binge Eating Scale was used to estimate the prevalence of BED in 180 women classified as overweight or obese. The levels of anandamide (AEA), 2-arachidonoylglycerol (2-AG), leptin, insulin, and orexin-A were measured by enzyme-linked immunosorbent assay kits. The subjects were genotyped for polymorphisms of FAAH gene using amplification refractory mutation system-polymerase chain reaction. Data were analyzed using SPSS software. About 41.6% (n = 75) of the subjects were diagnosed with BED. Women with BED exhibited significantly higher levels of AEA, 2-AG, leptin, and insulin compared to non-BED women (P < .05). Binary logistic regression analysis also showed that AEA, leptin, and insulin were the predictors of having BED after adjusting for body mass index (P < .05). In addition, the frequency of A allele of FAAH gene was higher in women with BED compared to women without BED; however, there were no significant differences between these 2 groups (P = .08). These results supported our hypothesis in the cases of AEA, 2-AG, leptin, and insulin but not orexin and FAAH gene polymorphisms. The findings of the current study provide further evidence concerning the role of these substances in BED.

Assessment of stress markers in restrained individuals following physical stress with and without sham CED activation.

INTRODUCTION: Law enforcement and pre-hospital care personnel often confront individuals who must be physically restrained. Many are under the influence of illicit substances, and law enforcement officers may need to use a controlled electrical device (CED) to gain control of the individual and they are often placed into the prone maximum restraint (PMR) position. These techniques have previously been evaluated for their physiologic effects. The purpose of this study was to investigate the psychological effects of anticipating and experiencing a sham CED activation in healthy human subjects who were exercised and restrained compared with no sham activation by assessing the differences in a panel of several known biomarkers of stress. METHODS: We performed a randomized, crossover controlled human subject trial to study the stress associated with exercise, physical exhaustion, and restraint with and without an added psychological stress simulating the field use of a CED. Twenty five total subjects; each subject performed two different trials each consisting of a brief period of intense exercise on a treadmill to exhaustion followed by placement in the PMR with and without induced psychological stress. Blood samples were collected for analysis pre and post exercise, as well as 10 min after completion of the exercise. A panel of hormones and stress markers were measured. RESULTS: We found no significant differences in any of the stress biomarkers measured between the two study groups. A trend towards higher levels of copeptin was measured in the sham CED activation arm. CONCLUSION: During a brief period of intense exercise followed by the psychological stress of anticipated CED application, there did not appear to be statistically significant changes in the stress panel of biomarkers measured, only a trend towards significance for higher copeptin levels in the patients exposed to the psychological stress.

The role of Orexin-A levels in epileptic seizure.

BACKGROUND: The aim of this study is to determine the usefulness of Orexin-A levels in differentiating between epileptic seizures and psychogenic non-epileptic seizures in patients presenting to the emergency service with epileptic seizure-type symptoms. METHODS: A total of 80 individuals were included in this study, including 59 who presented to the emergency service within the first four hours of having been diagnosed with generalized tonic-clonic seizures (39 with epileptic seizures (ES) and 20 with pseudoseizures (PNES) and 21 controls. Orexin-A levels were measured in venous blood samples. RESULTS: The mean Orexin-A levels were 5.16 ng/mL in the control group, 7.17 ng/mL in the PNES group, and 11.08 ng/mL in the ES group (Table 1). The mean Orexin-A level of the ES group was significantly different from both the control group and the PNES group (Table 1, p < 0.001); the difference between the control group and the PNES group was not significant (p > 0.05). CONCLUSIONS: Results of this study suggest that blood Orexin-A may be an effective biomarker in the differential diagnosis of epileptic seizures/psychogenic non-epileptic seizures in patients presenting to the emergency service with an epileptic seizure-type clinical picture.

CSF and serum ferritin levels in narcolepsy type 1 comorbid with restless legs syndrome.

OBJECTIVES: To investigate whether cerebrospinal fluid (CSF) and serum ferritin levels differ between patients with narcolepsy type 1 (NT1) comorbid with restless legs syndrome (RLS) or periodic leg movements during sleep (PLMS), and patients with NT1 or controls without comorbid RLS or PLMS. METHODS: Sixty-six drug-free patients with NT1 (44 males, age 38.5 years [14-81]) were enrolled, including 20 with RLS, 18 with PLMS index ≥15/h (six with both RLS and PLMS). Thirty-eight drug-free patients (12 males, age 22.5 years [12-61]) referred for sleepiness complaint, but without central hypersomnia, RLS, PLMS were included as controls. Clinical, electrophysiological and biological (CSF/serum ferritin, orexin [ORX]) data were quantified. RESULTS: NT1 patients with and without RLS did not differ for age, gender, and body mass index (BMI). No between-group differences were found for CSF ferritin, ORX, and serum ferritin levels. No CSF ferritin, ORX, and serum ferritin level differences were found between NT1 patients with and without PLMS, or with RLS or PLMS versus not. CSF-ferritin levels were not different between NT1 and controls in adjusted analyses. CSF-ferritin levels in the whole population correlated positively with age, serum-ferritin, BMI, negatively with ORX, but not with PLMS index. In NT1, CSF-ferritin levels correlated with age and serum-ferritin but not with PLMS. CONCLUSION: The absence of CSF ferritin deficiency in NT1 with comorbid RLS or PLMS indicates normal brain iron levels in that condition. This result suggests that the frequent association between RLS, PLMS, and NT1 is not based on alterations in brain iron metabolism, a pathophysiological mechanism involved in primary RLS.

Acute assessment of subjective appetite and implicated hormones after a hypnosis-induced hallucinated meal: a randomized cross-over pilot trial.

The use of hypnosis can generate hallucinatory phenomena, which ranged from vivid/auditory imagery to fully developed "hallucinations" in selected people. The aim of this pilot trial was investigating the acute effects of a hypnosis-induced hallucinated breakfast (HB) compared to those of a real breakfast (RB) on subjective appetite and appetite-regulating hormones in highly hypnotizable individuals. Eight healthy post-menopausal women were recruited to consume two meals: the HB and the RB in a randomized crossover design. Participants underwent appetite sensations measurements (before meal and each 30-min until 270-min) and blood sample collection (at 0, 20, 60, 90, 180-min). A 3-day food-record was filled after each meal. The adjusted repeated measures ANCOVA did not show any meal×time interactions on subjective appetite postprandially. As expected, significantly higher glucose (p < 0.001), insulin (p < 0.001), and lower free fatty acid (p < 0.001) concentrations were found after the RB, but not following HB. Furthermore, RB significantly increased postprandial levels of glucagon-like-peptide-1 and peptide-YY at 20, 60, 90 and 180-min, whereas acylated-ghrelin and leptin levels did not differ. Postprandial neuropeptide-Y and orexin-A values significantly increased at different time-points after RB, but not following HB, while α-melanocyte-stimulating hormone levels enhanced after HB only. Energy intakes were significantly lower after HB on the test-day only (HB = 1146.6 ± 343.8 vs RB = 1634.7 ± 274.2 kcal/d; p = 0.003). Appetite sensation might be modulated by fully developed meal "hallucination" induced by hypnosis, likely affecting brain-peptides implicated in the appetite regulation. However, further studies are needed to verify these results obtained in a highly selected group of individuals. NCT03934580.

Increased minimum alveolar concentration-awake of Sevoflurane in women of breast surgery with sleep disorders.

BACKGROUND: Sleep disorders are commonly encountered in clinic. Evidences showed that sleep deprivation may modulate the effectiveness of general anesthetics in rats. However, this phenomenon has not been explored in humans. The study aimed to investigate whether the hypnotic potency of sevoflurane in patients with sleep disorders differ from patients with normal sleep habits. METHODS: We recruited 44 patients scheduled for elective breast surgery and eventually analyzed 38 patients, including 19 subjects with normal sleep habits and 19 subjects with sleep disorders. According to the Dixon 'up-and-down' design, patients received sevoflurane at preselected concentrations starting at 1.0 vol%. After a steady-state period, a verbal command for testing awakening was performed. Based on the negative or positive response to the verbal command, we decreased or increased the concentration of sevoflurane by 0.2 vol% in the next patient accordingly. Plasma orexin-A was also measured before observation. RESULTS: The MACawake of sevoflurane was 0.80% [95% confidence interval (CI), 0.683-0.926%] in the sleep disordered group vs 0.60% [95% CI, 0.493-0.689%] in the control group. The relative median potency between groups was 0.750 (95% CI, 0.236-0.969). Patients with sleep disorders had significantly higher orexin-A levels than control (72.17 ± 18.24 vs. 36.16 ± 14.18 pg/mL). A significant, positive relationship was detected between orexin-A level and probability of awakening (OR = 1.081, 95% CI is 1.020-1.146, P = 0.008). CONCLUSIONS: MACawake of sevoflurane is higher in mild-aged women of breast surgery with sleep disorders compared to those with normal sleep habits. The increased anesthetic requirement may be related to changes of orexin-A levels. These findings suggest that sleep may have a potential impact on clinical anesthesia, including changes of sensitivity to anesthetics or postoperative complications. Further research is needed to confirm this hypothesis. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1800016022), date of registration 07 May 2018.

Increase of orexin A in the peripheral blood of adolescents with Internet gaming disorder.

BACKGROUND AND AIMS: Overindulgence in Internet gaming, which is related to rapid development of the online game industry, can cause a psychiatric disorder known as Internet gaming disorder (IGD). The number of adolescents with IGD is on the rise in countries with developed Internet technologies, such as South Korea. Therefore, it is important to develop biomarkers to detect patients at high risk of IGD. This study investigated expression levels of proteins in the blood of adolescents to provide insight into the development of biomarkers. METHODS: We collected blood samples from 73 subjects [40 healthy adolescents (Internet gaming control, IGC) and 33 adolescents with IGD] between 13:00 and 15:00. We analyzed the expression levels of orexin A, oxytocin, cortisol, melatonin, BDNF, sICAM-1, RANTES, and NCAM using multiplex assay kits. RESULTS: Orexin A was significantly (p = .016) elevated in the IGD group and the expression levels of melatonin tended to be higher (p = .055) in the IGD group. On the other hand, increased Internet gaming time in the IGD group was negatively correlated (p = .041) with expression of BDNF. On the contrary, sICAM-1 associated with inflammation exhibited the tendency of the positive correlation (p = .073) with Internet gaming time in the IGD group. DISCUSSION AND CONCLUSIONS: We identified elevation of orexin A in the peripheral blood of adolescents with IGD and a negative correlation between Internet gaming time and BDNF in adolescents with IGD. Our results provide useful information to understand the pathophysiology of IGD in adolescents.

Orexin A in adolescents with anxiety disorders.

Objectives: The relationships between orexins and stress-related conditions have been well documented in animal studies. However, human studies confirming this relationship are limited. The aim of this study was to investigate the association between orexin-A and anxiety disorders in adolescents. Additionally, we aimed to examine the relationship between orexin-A and cortisol levels in those with anxiety disorders.Methods: A total of 56 medication-free adolescents diagnosed with any anxiety disorder, except for specific phobias, and 32 healthy controls were included in this study. Depression, state and trait anxiety levels of the participants were measured using self-report scales. Orexin-A and cortisol levels were measured by an enzyme-linked immunosorbent assay (ELISA).Results: Analysis of covariance (ANCOVA) indicated that serum orexin-A levels were significantly higher in the anxiety disorder group than in the control group while controlling for age, sex and depression levels. After controlling for age and sex, orexin-A levels were positively and negatively correlated to depression and cortisol levels, respectively. In addition, a positive correlation trend between trait anxiety and orexin-A was found.Conclusions: Orexin-A levels are higher in adolescents with anxiety disorder; however, depressive symptoms should be considered when investigating this relationship.

Involvement of orexin A in nocturnal melatonin secretion into the cerebrospinal fluid and the blood plasma in seasonal sheep.

In sheep, differences in orexin A (OXA) gene expression and activity are related to changes in energy demand and seasonal reproduction. However, the mechanism by which and the key place where the OXA signal is integrated with photoperiod, whose main biochemical expression is melatonin (MEL), remain unknown. We examined the effects of cisterna magna injections of OXA (0.3 µg/kg body weight) on nocturnal cerebrospinal fluid (CSF) and plasma MEL concentrations; mRNA and protein expression of two rate-limiting enzymes for MEL biosynthesis, tryptophan 5-hydroxylase-1 (TPH1) and arylalkylamine-N-acetyltransferase (AA-NAT); and OXA receptor (OX1R, OX2R) expression in the pineal gland (PG) obtained from twenty ewes during the short-day (SD) and long-day (LD) seasons. OXA increased (P < 0.001) CSF and plasma MEL concentrations regardless of the season. Plasma MEL was positively correlated (P < 0.001) with CSF MEL in the OXA-treated sheep in both seasons. OXA had no effect (P > 0.05) on TPH1 transcript or protein level but upregulated (P < 0.05) AA-NAT mRNA and protein expression in both seasons. OXA enhanced (P < 0.05) OX1R mRNA level only during the LD season. Our results show that the endocrine activity of the ovine PG is regulated by day length and non-photic signals via hypothalamic OXA. These results are important for understanding the work of the biological clock and recognizing mechanisms responsible for the adaptation of seasonal animals to the changing external environment conditions. OXA and MEL are both involved in the regulation of the sleep-wakefulness system, therefore our results can be used in the study on the circadian rhythm disorders in humans (e.g. jet lag, insomnia, seasonal depression).