Sweet taste perception not altered after acute sleep deprivation in healthy young men

Background

We hypothesized that acutely sleep-deprived participants would rate ascending concentrations of sucrose as more intense and pleasant, than they would do after one night of normal sleep. Such a finding would offer a potential mechanism through which acute sleep loss could promote overeating in humans.

Method

A total of 16 healthy normal-weight men participated in 2 conditions: sleep (permitted between 22:30 and 06:30 h) and total sleep deprivation (TSD) respectively. On the morning after regular sleep and TSD, circulating concentrations of ghrelin and glucose were measured. In addition, participants hunger level was assessed by means of visual analogue scales, both before and after a caloric preload. Finally, following the preload, participants rated both intensity and pleasantness of six orally presented yogurt probes with varying sucrose concentrations (2–29?%).

Results

Feelings of hunger were significantly more intense under both fasted and sated conditions when subjects were sleep-deprived. In contrast, the change in hunger induced by the preload was similar between the sleep and TSD conditions. Plasma concentrations of ghrelin were significantly higher under conditions of TSD, whereas plasma glucose did not differ between the conditions. No effects were found either on sweet taste intensity or on pleasantness after TSD.

Conclusion

One night of TSD increases morning plasma concentrations of the hunger-promoting hormone ghrelin in healthy young men. In contrast, sweet taste perception was not affected by nocturnal wakefulness. This suggests that an altered sweet taste perception is an unlikely mechanism by which TSD enhances food intake.     

The red wine maximization test: Drinking histamine rich wine induces a transient increase in plasma diamine oxidase activity in healthy volunteers

Inflammation Research -     

Sleep deprivation in the rat: III. Total sleep deprivation

Ten rats were subjected to total sleep deprivation (TSD) by the disk apparatus. All TSD rats died or were sacrificed when death seemed imminent within 11-32 days. No anatomical cause of death was identified. All TSD rats showed a debilitated appearance, lesions on their tails and paws, and weight loss in spite of increased food intake. Their yoked control (TSC) rats remained healthy. Since dehydration was ruled out and several measures indicated accelerated use rather than failure to absorb nutrients, the food-weight changes in TSD rats were attributed to increased energy expenditure (EE). The measurement of EE, based upon caloric value of food, weight, and wastes, indicated that all TSD rats increased EE, with mean levels reaching more than twice baseline values.     

The effect of total sleep deprivation on plasma melatonin and cortisol in healthy human volunteers

Twelve healthy volunteers were included in this study. Baseline curves for melatonin and cortisol were obtained after one night of adaptation to laboratory conditions. From 10:00 p.m. to 6:00 a.m., blood samples were drawn every hour. On the third night, the subjects were kept awake at the sleep unit. Curves for the two hormones were then obtained after 36 h of total sleep deprivation (SD). The levels of these hormones were evaluated by calculating the area under the curve at each hour in both situations (basal and after sleep deprivation). It was found that the melatonin levels were increased after sleep deprivation, whereas the cortisol levels remained the same. These results suggest a mechanism by which a reset of abnormal rhythms can occur in depression.     

Acute LPS inhalation in healthy volunteers induces dendritic cell maturation in vivo

BACKGROUND: We have been studying the innate immune response of airways cells of healthy human volunteers to inhaled LPS, a Toll-like receptor 4 (TLR4) ligand, and have shown that macrophage phagocytic capacity is blunted. OBJECTIVE: Because a primary feature of dendritic cell (DC) maturation is a loss of phagocytic capacity, we sought to determine whether acute LPS inhalation in healthy volunteers promotes DC maturation in vivo. METHODS: Phagocytosis (IgG-opsonized zymosan particles) and cell-surface phenotypes were analyzed by flow cytometry of induced sputum cells obtained before and 6 hours after Clinical Center Reference Endotoxin (CCRE; 20,000 EU) inhalation in 9 healthy volunteers. RESULTS: Neutrophils were elevated in the airways after CCRE inhalation (67% +/- 6% vs 37% +/- 6%; P < .05). Phagocytosis (monocytes, macrophages) was blunted (73%, 46%; P < .05) and negatively correlated with PMN influx ( R = -0.73; P < .05) after CCRE inhalation. GM-CSF and IL-1beta, potent DC maturation agents, were elevated after versus before CCRE inhalation (217 pg/mL +/- 103 pg/mL vs 722 pg/mL +/- 202 pg/mL; 83 pg/mL +/- 24 pg/mL vs 148 pg/mL +/- 37 pg/mL, respectively; P < .05). Markers of DC maturation (CD80, CD86, HLA-DR) were upregulated on monocytes and macrophages ( P < .05), and discrete populations of mature DC were observed ( P < .05) after CCRE inhalation. CONCLUSION: Inhaled LPS, directly through TLR4 stimulation of immature DC and/or indirectly through stimulation of GM-CSF and IL-1beta, induces pulmonary DC maturation in vivo . Inhaled LPS may enhance allergic airways responses to air pollution through its ability to induce DC maturation.     

Effect of sleep deprivation on NREM sleep ERPs and related activity at sleep onset.

This research assessed the impact of one night of sleep deprivation on the amplitudes of NREM-sleep event-related potentials (NREM ERPs) and on the frequency of occurrence of related electroencephalogram activity including sleep spindles, arousals, K-complexes, and vertex sharp waves (VSWs). The NREM ERPs identified included P220, N350, P450, N550 and P900. During a pre-deprivation night, ten subjects took two 20-min naps separated by a 20-min break at their normal bedtime. Brief tones were presented at three intensity levels (60, 75 and 90 dB) with a 5-s interstimulus interval. Following these naps, subjects were kept awake until their normal bedtime the following day. At that time, they repeated the two-nap procedure. The ERPs obtained for each tone and wake/sleep state for pre- and post-deprivation conditions were analyzed using repeated measures statistical procedures. As anticipated, NREM ERP amplitudes recorded both pre- and post-deprivation increased with tone intensity and with approaching sleep. Also, sleep deprivation was associated with more rapid sleep onset, reduced arousability, and greater spindle production. While sleep deprivation had no effect on the amplitude of P220. Post-deprivation amplitudes of N350, N550 and P900 were greater, especially following the 90-dB tone. There was a corresponding increase in VSWs and K-complexes. These findings are inconsistent with the view that NREM ERPs reflect arousal. The underlying mechanism(s) may facilitate initiation and maintenance of sleep.     

Effect of sleep deprivation on cholesterol metabolism and triglyceridaemia in male volunteers

Summary The effect of 5-day sleep deprivation (SD) on cholesterol metabolism, together with triglyceridaemia, was studied in seven healthy male volunteers. A 3-day control period was followed by 5 days (120 h) complete SD and 4 days recovery. Blood was collected at 9 a.m. and at 9 p.m. Vastus lateralis muscle biopsy was performed during the control period, on the 5th day of SD, and on day 3 of recovery. The value of muscle cholesterol was related to the non-collagen protein content. The plasma triglycerides (TG) varied in a circadian biorhythm, the amplitude of which declined gradually during SD. The morning triglyceridaemia was significantly decreased on days 3–5 of SD (35%–79% of initial values). On days 4 and 5 of SD, plasma cholesterol fell significantly to 78% and 88% of control values, respectively. The ratio of its esterified to unesterified fractions remained unchanged throughout SD. Basal activity of lecithin cholesterol acyltransferase (LCAT) showed no diurnal biorhythm; on the last 2 days of SD, LCAT activity fell significantly to 71%–80%. In contrast, the decrease in fractional esterification rate (FER) was insignificant. In the vastus lateralis muscle, total cholesterol (TC) was decreased by 40% at the end of SD, the reduction being greater for cholesterol esters (CE) (by 63%) than for free cholesterol (FC) (by 36%). The relative proportion of CE significantly decreased from an initial 14.7% to 9.2% on the last day of SD. During recovery after SD, plasma cholesterol and TG slowly returned to normal. LCAT activity and FER recovered quickly, within 48 h. In the muscle, recovery was characterized by cholesterol accumulation, particularly by that of its esterified fraction: TC increased by 11%, CE by 57%, and FC by 3% over the respective control values. The percentage of CE rose to 20.7%. It may be concluded that SD has a profound influence on cholesterol metabolism. Some changes resemble those characterizing cardiovascular diseases.     

The effects of mirtazapine on sleep: a placebo controlled,double-blind study in young healthy volunteers

STUDY OBJECTIVES: Mirtazapine is classified as a noradrenergic and specific serotonergic antidepressant. This study aims at objectively investigating the effects of single-dose mirtazapine on sleep of healthy volunteers. DESIGN AND SETTING: We studied the effect of acute administration of mirtazapine (30 mg) on the sleep polysomnogram, using a double-blind, placebo-controlled design. Subjects spent 3 consecutive nights in the laboratory. First night allowed for adaptation to the laboratory and application of electroencephalogram electrodes, while the second and third nights were reserved for recording baseline sleep and studying the effects of drug treatment, respectively. PARTICIPANTS: Young healthy volunteers (n=20), with a mean age of 24 years, were randomly separated into two groups: placebo (n=10) and mirtazapine (n=10). INTERVENTIONS: On the third night, subjects received either placebo or mirtazapine. Comparisons were made between sleep variables from baseline values in both groups. Independent samples t-test was utilized to evaluate the differences between the two groups. MEASUREMENT AND RESULTS: Mirtazapine improved the variables related to sleep continuity when compared with placebo. It increased the sleep efficiency index, while decreasing the number of awakenings and their duration. The slow wave sleep time was increased, while the stage 1 sleep time was decreased significantly. There was no significant effect on rapid eye movement sleep variables. CONCLUSION: Our findings suggest that mirtazapine has considerable effects on slow wave sleep. Further studies are recommended to investigate the efficiency of antidepressants, in respect to the effects of 5-HT2 blockade on slow wave sleep.     

Experimental manipulation of cognitive control processes causes an increase in communication disturbances in healthy volunteers

BACKGROUND: Although communication disturbances (CD) have been associated with poor cognitive control, it is unclear whether they are associated specifically with poor cognitive control or with poor cognition in general. The current research examined whether (a) two specific components of cognitive control, working memory and interference resolution, were associated with CD, and (b) associations between CD and cognitive control could be accounted for by generalized poor cognitive performance. METHOD: In this study, as healthy volunteers spoke, the level of cognitive demands was experimentally increased, thereby simulating cognitive deficits (i.e. a reduction in the degree to which certain types of cognitive processes could be used for speech). Hence, this research examined whether simulated cognitive deficits would cause an increase in CD. Participants also completed separate cognitive tasks that assessed working memory, interference resolution and general cognitive ability. RESULTS: An increase in working memory demands caused an increase in CD. Moreover, working memory demands interacted with interference resolution demands, with the greatest amount of CD caused by both high working memory and high interference resolution demands. By contrast, increasing another cognitive demand, sustained attention, did not increase CD. Furthermore, performance on separate working memory and interference resolution tasks interacted to predict CD on the experimental speech task. However, performance on a psychometrically matched cognitive task did not predict CD. CONCLUSION: Overall, the current study provides evidence that working memory and interference resolution may be specifically associated with CD and that manipulations of these cognitive control processes can cause an increase in CD.     

Oral administration of interferon-alpha induces a transient decline in oral mucosal immunoglobulins and an increase in interleukin-5.

Although administration of interferon-alpha (IFN-alpha) via the oral-mucosal route has shown efficacy in a variety of human and animal diseases, the mechanism of action of orally administered IFN is not clearly understood. To assess the possibility that IFN-alpha given via a lozenge alters the local mucosal immune system, immunoglobulins (Ig) and cytokines were measured in salivary secretions. Volunteers were given low doses of IFN-alpha and saliva was collected over a 24-h period. IgA and precursor IgM were measured by sandwich enzyme-linked immunosorbent assay (ELISA). Salivary concentrations of interleukin-5 (IL-5), the T helper cytokine primarily responsible for the switch from IgM to IgA, were also determined. After oral administration of IFN-alpha, there was an initial decline in IgM and IgA followed by a return to baseline levels by 8-24 h. This change in Ig concentration was associated with a gradual increase in IL-5, consistent with the return of Ig to baseline as a result of modulation by Ig-mediating cytokines.     

Plasma melatonin rhythms in young and older humans during sleep, sleep deprivation, and wake

STUDY OBJECTIVES: To determine the effects of sleep and sleep deprivation on plasma melatonin concentrations in humans and whether these effects are age-dependent. DESIGN: At least 2 weeks of regular at-home, sleep/wake schedule followed by 3 baseline days in the laboratory and at least one constant routine (sleep deprivation). SETTING: General Clinical Research Center (GCRC), Brigham and Women's Hospital, Boston, MA. PARTICIPANTS: In Study 1, one group (<10 lux when awake) of 19 young men (18-30 y) plus a second group (<2 lux when awake) of 15 young men (20-28 y) and 10 young women (19-27 y); in Study 2, 90 young men (18-30 y), 18 older women (65-81 y), and 11 older men (64-75 y). All participants were in good health, as determined by medical and psychological screening. INTERVENTIONS: One to three constant routines with interspersed inversion of the sleep/wake cycle in those with multiple constant routines. MEASUREMENTS AND RESULTS: Examination of plasma melatonin concentrations and core body temperature. Study 1. There was a small, but significant effect of sleep deprivation of up to 50 hours on melatonin concentrations (increase of 9.81 +/- 3.73%, P <0.05, compared to normally timed melatonin). There was also an effect of circadian phase angle with the prior sleep episode, such that if melatonin onset occurred <8 hours after wake time, the amplitude was significantly lower (22.4% +/- 4.79%, P <0.001). Study 2. In comparing melatonin concentrations during sleep to the same hours during constant wakefulness, in young men, melatonin amplitude was 6.7% +/- 2.1% higher(P <0.001) during the sleep episode. In older men, melatonin amplitude was 37.0% +/- 12.5% lower (P <0.05) during the sleep episode and in older women, melatonin amplitude was non-significantly 10.9% +/- 8.38% lower (P = 0.13) during the sleep episode. CONCLUSIONS: Both sleep and sleep deprivation likely influence melatonin amplitude, and the effect of sleep on melatonin appears to be age dependent.     

Total sleep deprivation followed by sleep phase advance and bright light therapy in drug-resistant mood disorders

BackgroundDrug-resistant depression is a major therapeutic issue in psychiatry and the development of non-drug therapies that treat drug-resistant depression is required. Sleep deprivation (SD) is a non-drug treatment classified as a form of chronotherapy in addition to bright light therapy (BLT) and sleep phase advance (SPA). Combined chronotherapy is hypothesized to improve drug-resistant depression. In this study, we investigated the benefits of total sleep deprivation (TSD) followed by SPA and BLT in drug-resistant depression alongside ongoing antidepressant medication and observed the added effectiveness of the combined chronotherapy.MethodsThirteen drug-resistant inpatients affected by a major depressive episode were studied. They were treated by TSD followed by SPA (three days) and BLT (five days) with ongoing drug treatment. Effectiveness was rated using the Hamilton Rating Scale for Depression (HAM-D), the Zung Self-Rating Depression Scale (SDS), and the Visual Analogue Scale (VAS) over 3 weeks.ResultsSignificant improvements of depressive symptoms were observed in both objective mood ratings (HAM-D) and subjective mood ratings (SDS and VAS). Eight out of 13 patients maintained this responsiveness (50% or greater changes in HAM-D) across the study period. Moreover, no patients dropped out of the combined chronotherapy procedure.LimitationsThe study did not have a placebo group, and more subjects may be needed.ConclusionThe trial of combined chronotherapy successfully induced rapid improvement in depressive symptoms in drug-resistant patients without early relapse or obvious side effects.     

Differential increase in the expression of heat shock protein family members during sleep deprivation and during sleep

Although sleep is thought to be restorative from prior wakeful activities, it is not clear what is being restored. To determine whether the synthesis of macromolecules is increased in the cerebral cortex during sleep, we subjected C57BL/6 mice to 6 hours of sleep deprivation and then screened the expression of 1176 genes of known function by using cDNA arrays. The expression of the heat shock proteins (HSP), endoplasmic reticulum protein (ERp72) and glucose-regulated protein (GRp78), was among the genes whose expression was significantly elevated in the cortex during sleep deprivation, whereas GRp78 and GRp94 mRNAs were elevated in the cortex during recovery sleep after sleep deprivation, as confirmed by conventional and quantitative real-time polymerase chain reaction and/or Northern analyses. A systematic evaluation of the expression of six heat shock protein family members (ERP72, GRp78, GRp94, HSP27, HSP70-1, and HSP84) in seven brain regions revealed increased mRNA levels in cortex, basal forebrain, hypothalamus, cerebellum and medulla during sleep deprivation, whereas increased mRNA levels during recovery sleep were limited to the cortex and medulla. Immunohistochemical studies identified increased numbers of GRp78-, GRp94-, and ERp72-immunoreactive cells in the dorsal and lateral cortex during sleep deprivation but, during recovery sleep, elevated numbers of these cells were found only in the lateral cortex. In the medulla, increased numbers of GRp94-immunoreactive cells were observed in nucleus tractus solitarius, dorsal motor nucleus of the vagus and the rostroventrolateral medulla during recovery sleep. The widespread increase of heat shock protein family mRNAs in brain during sleep deprivation may be a neuroprotective response to prolonged wakefulness. In contrast, the relatively limited heat shock protein family mRNA expression during recovery sleep may be related to the role of heat shock proteins in protein biogenesis and thus to the restorative function of sleep.     

清醒健康志愿者短暂肢体缺血的可接受性和安全性评价

目的: 评估清醒健康志愿者短暂肢体缺血的安全性和可接受性。方法: 选择60名20-30岁健康志愿者,男女各半,利用血压计袖带的充气/放气进行3个循环的非优势上肢缺血再灌注,每个循环为缺血5 min/再灌注5 min,充气压力为200 mmHg。此过程中持续监测心率、血压、脉搏氧饱和度等生命体征,操作结束后用调查问卷(主要以0-10分的数字评分法为量化尺度)评估可接受性和不适感觉,于第3 d重复进行1次同样的问卷调查,以评估问卷的可信度,保证结果的可靠性。结果: 短暂肢体缺血中,志愿者的心率、血压和脉搏氧饱和度均波动在正常范围内。56.6%男性和66.7%女性的可接受度为7-8分,56.7%志愿者的舒适程度在4-6分,86.7%志愿者认为麻木感是最主要的不适感觉,46.6%男性和50.9%女性的麻木感评分在7-8分,每个循环肢体缺血中麻木感持续2-5 min,再灌注后1-2 min消失。男女间的可接受度和不适感觉无显著差异。问卷具有良好的重测信度(组内相关系数为0.990)。结论: 短暂肢体缺血是一种乐于被清醒健康志愿者所接受的、安全的远程缺血处理方法。     

Chronotype and sex effects on sleep architecture and quantitative sleep EEG in healthy young adults

STUDY OBJECTIVES: To evaluate the influence of chronotype (morning types and evening types) on sleep stages and quantitative sleep electroencephalograms when constraints on the sleep schedule are minimal and when sex difference is taken into account. DESIGN: A 48-hour session in the laboratory, including 2 nights of polysomnography, preceded by 7 days of ambulatory actigraphy. SETTING: Chronobiology laboratory. PARTICIPANTS: Twenty-four healthy young subjects: 12 morning types and 12 evening types selected by questionnaire. Each group included 6 men and 6 women. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: A polysomnography night of 8 hours in duration was recorded according to preferred sleep schedule. Sleep-stage analysis revealed that morning types and evening types did not differ in sleep architecture. However, morning-type men showed a higher percentage of stage 1 sleep and lower sleep efficiency than evening-type men. Electroencephalogram spectral analysis was conducted in non-rapid eye movement sleep for 6 frequency bands. Morning types had more spectral power in low sigma (12-14 Hz) compared with evening types. The most robust difference between women and men was found in high sigma (14-16 Hz) and was not present between chronotypes. The decay rate of slow-wave activity (1-5 Hz) tended to be faster in morning types compared with evening types (P = .06). This rate was almost identical for women and men. CONCLUSIONS: These results agree with the hypothesis that homeostatic sleep regulation differs between morning types and evening types, with morning types showing indications of a higher rate of dissipation of sleep pressure during the night. Morningness-eveningness seems to affect sleep in a sex-specific manner, with men being more affected by their chronotype.     

The effects of total sleep deprivation, selective sleep interruption and sleep recovery on pain tolerance thresholds in healthy subjects

The aim of this study was to compare the effects of total sleep deprivation (TSD), rapid eye movement (REM) sleep and slow wave sleep (SWS) interruption and sleep recovery on mechanical and thermal pain sensitivity in healthy adults. Nine healthy male volunteers (age 26--43 years) were randomly assigned in this double blind and crossover study to undergo either REM sleep or SWS interruption. Periods of 6 consecutive laboratory nights separated by at least 2 weeks were designed as follows: N1 Adaptation night; N2 Baseline night; N3 Total sleep deprivation (40 h); N4 and N5 SWS or REM sleep interruption; N6 Recovery. Sleep was recorded and scored using standard methods. Tolerance thresholds to mechanical and thermal pain were assessed using an electronic pressure dolorimeter and a thermode operating on a Peltier principle. Relative to baseline levels, TSD decreased significantly mechanical pain thresholds (-8%). Both REM sleep and SWS interruption tended to decrease mechanical pain thresholds. Recovery sleep, after SWS interruption produced a significant increase in mechanical pain thresholds (+ 15%). Recovery sleep after REM sleep interruption did not significantly increase mechanical pain thresholds. No significant differences in thermal pain thresholds were detected between and within periods. In conclusion this experimental study in healthy adult volunteers has demonstrated an hyperalgesic effect related to 40 h TSD and an analgesic effect related to SWS recovery. The analgesic effect of SWS recovery is apparently greater than the analgesia induced by level I (World Health Organization) analgesic compounds in mechanical pain experiments in healthy volunteers.     

The acute effects of androstenedione supplementation in healthy young males.

We examined the effects of androstenedione supplementation on the hormonal profile of 10 males and its interaction with resistance exercise. Baseline testosterone, luteinizing hormone, estradiol, and androstenedione concentrations were established by venous sampling at 3 hr intervals over 24 hr. Subjects ingested 200 mg of androstenedione daily for 2 days, with second and third day blood samples. Two weeks later, they ingested androstenedione or a placebo for 2 days, in a double-blind, cross-over design. On day 2, they performed heavy resistance exercise with blood sampled before, after, and 90 min post. The supplement elevated plasma androstenedione 2--3-fold and luteinizing hormone approximately 70% but did not alter testosterone concentration. Exercise elevated testosterone, with no difference between conditions. Exercise in the supplemented condition significantly elevated plasma estradiol by approximately 83% for 90 min. Androstenedione supplementation, thus, is unlikely to provide male athletes with any anabolic benefit and, with heavy resistance exercise, elevates estrogen.     

Enhanced slow-wave activity within NREM sleep in the cortical and subcortical EEG of the cat after sleep deprivation.

Electroencephalograms (EEGs) of the cortex and of seven subcortical structures were recorded during two baseline days and during a recovery day following a 12-hour period of sleep deprivation (SD) in eight cats. The EEGs were analyzed by visual scoring and by spectral analysis. The following subcortical structures were studied: hippocampus, amygdala, hypothalamus, nucleus centralis lateralis of the thalamus, septum, nucleus caudatus and substantia nigra. The EEGs of all brain structures exhibited sleep state-dependent changes. In general, slow-wave activity (SWA, 0.5-4.0 Hz) during nonrapid eye movement (NREM) sleep exceeded that of REM sleep. The power spectra (0.5-24.5 Hz) in NREM, as well as the relationship between the power spectra of NREM and REM sleep, differed between the recording sites. Moreover, the rate of increase of SWA in the course of an NREM episode and the rate of decrease of SWA at the transition from NREM to REM sleep differed between the brain structures. During the first 12 hours following SD, the duration of NREM increased due to a prolongation of the NREM episodes. REM increased by a rise in the number of REM episodes. During the same period, the NREM EEG power density in the delta and theta frequencies was enhanced in all brain structures. Furthermore, in all structures the enhancement of SWA was most pronounced at the beginning of the recovery period and gradually declined thereafter. SD also induced a rise in the rate of increase of SWA in the NREM episodes in all recording sites. This indicates that the enhancement of EEG power density was not only due to prolongation of the NREM episodes. The EEG activity during REM was barely affected by the SD. It is concluded that, in all brain structures studied, the EEG during NREM is characterized by high levels of SWA. Furthermore, in each brain structure, SWA within NREM sleep is enhanced after a prolonged vigil. These data may indicate that SWA reflects a recovery process in cortical and subcortical structures.