Medical History of Optic Chiasm Compression in Patients With Pituitary Insufficiency Affects Skin Temperature and Its Relation to Sleep

The hypothalamus is crucially involved in the circadian timing of the sleep-wake rhythm, yet also accommodates the most important thermoregulatory neuronal network. We have shown before that adults with pituitary insufficiency and history of chiasm compression due to a tumor with suprasellar extension fall asleep later and sleep shorter than those without such history and presumed hypothalamic involvement. To solidify the hypothesized link between vigilance and thermoregulation by the hypothalamus, we aimed to test the hypothesis that the presumed hypothalamic impairment in these patients also affects skin temperature and its association with sleep onset. In a case-control study of 50 patients (54.7?±?14.5 yrs of age, 30 males) with pituitary insufficiency, 33 of whom had a history of chiasm compression, ambulatory distal and proximal skin temperatures were assessed continuously for 24?h. Sleep parameters were assessed via questionnaire. Group differences in mean skin temperature, calculated over the wake and sleep periods separately, and group differences in the strength of association between pre-sleep skin temperature and sleep onset latency were compared. Results showed that patients with a medical history of chiasm compression had lower proximal skin temperature during the day (34.1°C?±?.7°C vs. 34.6°C?±?.7°C, p?=?.045). Additionally, the typical association between sleep onset latency and pre-sleep distal-to-proximal skin temperature gradient was absent in these patients (r?=??.01, p?=?.96), whereas it was unimpaired in those without chiasm compression (r?=??.61, p?=?.02). Thus, patients with history of chiasm compression show impaired skin temperature regulation in association with disturbed sleep. The findings support the hypothesis that a medical history of chiasm compression affects hypothalamic regulation of both vigilance and temperature, possibly by chronically affecting relevant nuclei, including the ventrolateral preoptic area and anterior hypothalamic preoptic area. (Corresponding Author: n.romeijn@nin.knaw.nl)     

Phase relationship between skin temperature and sleep-wake rhythms in women with vascular dysregulation and controls under real-life conditions

The aim of the study was to investigate whether women with primary vascular dysregulation (VD; main symptoms of thermal discomfort with cold extremities) and difficulties initiating sleep (DIS) exhibit a disturbed phase of entrainment (Ψ) under everyday life conditions. The authors predicted a phase delay of the distal-proximal skin temperature gradient and salivary melatonin rhythms with respect to the sleep-wake cycle in women with VD and DIS (WVD) compared to controls (CON), similar to that found in their previous constant-routine laboratory data. A total of 41 young healthy women, 20 with WVD and 21 matched CON without VD and normal sleep onset latency (SOL), were investigated under ambulatory conditions (following their habitual bedtimes) during 7 days of continuous recording of skin temperatures, sleep-wake cycles monitored by actimetry and sleep-wake diaries, and single evening saliva collections for determining the circadian marker of dim light melatonin onset (DLMO). Compared to CON, WVD showed increased distal vasoconstriction at midday and in the evening, as indicated by lower distal (DIST; hands and feet) and foot-calf skin temperatures, and distal-proximal skin temperature gradients (p相似文献   

Divergent roles of plasma osmolality and the baroreflex on sweating and skin blood flow

Plasma hyperosmolality and baroreceptor unloading have been shown to independently influence the heat loss responses of sweating and cutaneous vasodilation. However, their combined effects remain unresolved. On four separate occasions, eight males were passively heated with a liquid-conditioned suit to 1.0°C above baseline core temperature during a resting isosmotic state (infusion of 0.9% NaCl saline) with (LBNP) and without (CON) application of lower-body negative pressure (-40 cmH2O) and during a hyperosmotic state (infusion of 3.0% NaCl saline) with (LBNP + HYP) and without (HYP) application of lower-body negative pressure. Forearm sweat rate (ventilated capsule) and skin blood flow (laser-Doppler), as well as core (esophageal) and mean skin temperatures, were measured continuously. Plasma osmolality increased by ～10 mosmol/kgH2O during HYP and HYP + LBNP conditions, whereas it remained unchanged during CON and LBNP (P ≤ 0.05). The change in mean body temperature (0.8 × core temperature + 0.2 × mean skin temperature) at the onset threshold for increases in cutaneous vascular conductance (CVC) was significantly greater during LBNP (0.56 ± 0.24°C) and HYP (0.69 ± 0.36°C) conditions compared with CON (0.28 ± 0.23°C, P ≤ 0.05). Additionally, the onset threshold for CVC during LBNP + HYP (0.88 ± 0.33°C) was significantly greater than CON and LBNP conditions (P ≤ 0.05). In contrast, onset thresholds for sweating were not different during LBNP (0.50 ± 0.18°C) compared with CON (0.46 ± 0.26°C, P = 0.950) but were elevated (P ≤ 0.05) similarly during HYP (0.91 ± 0.37°C) and LBNP + HYP (0.94 ± 0.40°C). Our findings show an additive effect of hyperosmolality and baroreceptor unloading on the onset threshold for increases in CVC during whole body heat stress. In contrast, the onset threshold for sweating during heat stress was only elevated by hyperosmolality with no effect of the baroreflex.     

Correlated fluctuations of daytime skin temperature and vigilance

Skin temperature shows spontaneous ultradian fluctuations during everyday-life wakefulness. Previous work showed that mild manipulations of skin temperature affect human sleep and vigilance, presumably by influencing neuronal systems involved in both thermal sensing and arousal regulation. We therefore examined whether fluctuations in skin temperature are associated with those in vigilance level under conditions similar to everyday-life situations requiring sustained attention. Eight healthy participants (30.1 ± 8.1 years, M ± SD) participated in a 2-day protocol, during which vigilance and skin temperature were assessed 4 times per day in a silent, dimly lit, temperature-controlled room. Vigilance was assessed by measuring reaction speed and lapses on a novel sustained vigilance task specifically designed to increase lapse rate and range of reaction times. Skin temperature was sampled at 30-second intervals from 3 locations: distal, intermediate, and proximal temperatures were obtained from the middle finger (T(finger) ), the wrist (T(wrist)), and the infraclavicular area (T(chest)), respectively. Furthermore, 3 distal to proximal gradients were calculated. Mixed-effect regression analyses were used to evaluate the association of the fluctuations in temperatures and gradients and those in response speed and lapse probability. Especially the spontaneous fluctuations in proximal temperature were negatively associated with fluctuations in response speed and positively with lapse rate. If individual T(chest) temperature ranges were classified into 10 deciles, they accounted for 23% of the variance in response speed and 11% of the variance in lapse rate. The findings indicate coupling between the spontaneous fluctuations in skin temperature and vigilance during the day and are compatible with the hypothesis of overlap in brain networks involved in the regulation of temperature and vigilance. From an applied point of view, especially proximal skin temperature assessment may be of use in vigilance monitoring.     

Towards a characterization of the locomotor activity rhythm of the supralittoral isopod Tylos europaeus

Freshly collected samples of Tylos europaeus from Korba beach (northeast of Tunisia) were housed in an environmental cabinet at controlled temperature (18°C?±?.5°C) and photoperiod. Locomotor activity was recorded under two photoperiodic regimens by infrared actography every 20?min by multichannel data loggers. One regimen simulated the natural light-dark cycle on the day of collection, whereas the second imposed a state of continuous darkness on all individuals. Under entraining conditions, the animals displayed rhythmic activity, in phase with the period of darkness, whereas in continuous darkness these isopods exhibited a strong endogenous rhythm with circadian and semidiurnal components at mean periods of τ (h:min)?=?25:09?±?01:02?h and τ?=?12:32?±?00:26?h, respectively. Under free-running conditions, this endogenous rhythm showed significant intraspecific variability.     

Characterization of the hypnotic effects of triazolam microinjections into the medial preoptic area.

We have previously reported that microinjections of the benzodiazepine hypnotic triazolam into the medial preoptic area (MPA) of the hypothalamus enhance sleep in rats. The present study further characterizes this effect, by examining its anatomical specificity, determining whether it is mediated by interaction with central benzodiazepine receptors, and assessing whether sleep induction is associated with changes in core temperature. It was found that microinjections of 0.25 and 0.5 micrograms triazolam into two nearby structures, the lateral preoptic area and diagonal band of Broca, failed to alter sleep. Total sleep time was enhanced by microinjection of triazolam into the MPA, and this effect was blocked by co-administration of the benzodiazepine receptor blocker RO 15-1788. Sleep enhancement by triazolam was not associated with significant alterations in core body temperature. These observations continue to suggest that the MPA may be a site which mediates the hypnotic effect of triazolam, and add to the growing body of data emphasizing the importance of hypothalamic function in the regulation of sleep and waking.     

Older poor-sleeping women display a smaller evening increase in melatonin secretion and lower values of melatonin and core body temperature than good sleepers

Melatonin concentration and core body temperature (CBT) follow endogenous circadian biological rhythms. In the evening, melatonin level increases and CBT decreases. These changes are involved in the regulation of the sleep-wake cycle. Therefore, the authors hypothesized that age-related changes in these rhythms affect sleep quality in older people. In a cross-sectional study design, 11 older poor-sleeping women (aged 62-72 yrs) and 9 older good-sleeping women (60-82 yrs) were compared with 10 younger good-sleeping women (23-28 yrs). The older groups were matched by age and body mass index. Sleep quality was assessed by the Pittsburgh Sleep Quality Index questionnaire. As an indicator of CBT, oral temperature was measured at 1-h intervals from 17:00 to 24:00?h. At the same time points, saliva samples were collected for determining melatonin levels by enzyme-linked immunosorbent assay (ELISA). The dim light melatonin onset (DLMO), characterizing the onset of melatonin production, was calculated. Evening changes in melatonin and CBT levels were tested by the Friedman test. Group comparisons were performed with independent samples tests. Predictors of sleep-onset latency (SOL) were assessed by regression analysis. Results show that the mean CBT decreased in the evening from 17:00 to 24:00?h in both young women (from 36.57°C to 36.25°C, p < .001) and older women (from 36.58°C to 35.88°C, p < .001), being lowest in the older poor sleepers (p < .05). During the same time period, mean melatonin levels increased in young women (from 16.2 to 54.1 pg/mL, p < .001) and older women (from 10.0 to 23.5 pg/mL, p < .001), being lowest among the older poor sleepers (from 20:00 to 24:00?h, p < .05 vs. young women). Older poor sleepers also showed a smaller increase in melatonin level from 17:00 to 24:00?h than older good sleepers (mean?±?SD: 7.0?±?9.63 pg/mL vs. 15.6?±?24.1 pg/mL, p = .013). Accordingly, the DLMO occurred at similar times in young (20:10?h) and older (19:57?h) good-sleeping women, but was delayed ～50?min in older poor-sleeping women (20:47?h). Older poor sleepers showed a shorter phase angle between DLMO and sleep onset, but a longer phase angle between CBT peak and sleep onset than young good sleepers, whereas older good sleepers had intermediate phase angles (insignificant). Regression analysis showed that the DLMO was a significant predictor of SOL in the older women (R(2)?=?0.64, p < .001), but not in the younger women. This indicates that melatonin production started later in those older women who needed more time to fall asleep. In conclusion, changes in melatonin level and CBT were intact in older poor sleepers in that evening melatonin increased and CBT decreased. However, poor sleepers showed a weaker evening increase in melatonin level, and their DLMO was delayed compared with good sleepers, suggesting that it is not primarily the absolute level of endogenous melatonin, but rather the timing of the circadian rhythm in evening melatonin secretion that might be related to disturbances in the sleep-wake cycle in older people.     

Local heating, but not indirect whole body heating, increases human skeletal muscle blood flow

For decades it was believed that direct and indirect heating (the latter of which elevates blood and core temperatures without directly heating the area being evaluated) increases skin but not skeletal muscle blood flow. Recent results, however, suggest that passive heating of the leg may increase muscle blood flow. Using the technique of positron-emission tomography, the present study tested the hypothesis that both direct and indirect heating increases muscle blood flow. Calf muscle and skin blood flows were evaluated from eight subjects during normothermic baseline, during local heating of the right calf [only the right calf was exposed to the heating source (water-perfused suit)], and during indirect whole body heat stress in which the left calf was not exposed to the heating source. Local heating increased intramuscular temperature of the right calf from 33.4 ± 1.0°C to 37.4 ± 0.8°C, without changing intestinal temperature. This stimulus increased muscle blood flow from 1.4 ± 0.5 to 2.3 ± 1.2 ml·100 g?1·min?1 (P < 0.05), whereas skin blood flow under the heating source increased from 0.7 ± 0.3 to 5.5 ± 1.5 ml·100 g?1·min?1 (P < 0.01). While whole body heat stress increased intestinal temperature by ～1°C, muscle blood flow in the calf that was not directly exposed to the water-perfused suit (i.e., indirect heating) did not increase during the whole body heat stress (normothermia: 1.6 ± 0.5 ml·100 g?1·min?1; heat stress: 1.7 ± 0.3 ml·100 g?1·min?1; P = 0.87). Whole body heating, however, reflexively increased calf skin blood flow (to 4.0 ± 1.5 ml·100 g?1·min?1) in the area not exposed to the water-perfused suit. These data show that local, but not indirect, heating increases calf skeletal muscle blood flow in humans. These results have important implications toward the reconsideration of previously accepted blood flow distribution during whole body heat stress.     

Large differences in peak oxygen uptake do not independently alter changes in core temperature and sweating during exercise

The independent influence of peak oxygen uptake (Vo(? peak)) on changes in thermoregulatory responses during exercise in a neutral climate has not been previously isolated because of complex interactions between Vo(? peak), metabolic heat production (H(prod)), body mass, and body surface area (BSA). It was hypothesized that Vo(? peak) does not independently alter changes in core temperature and sweating during exercise. Fourteen males, 7 high (HI) Vo(? peak): 60.1 ± 4.5 ml·kg?1·min?1; 7 low (LO) Vo(? peak): 40.3 ± 2.9 ml·kg?1·min?1 matched for body mass (HI: 78.2 ± 6.1 kg; LO: 78.7 ± 7.1 kg) and BSA (HI: 1.97 ± 0.08 m2; LO: 1.94 ± 0.08 m2), cycled for 60-min at 1) a fixed heat production (FHP trial) and 2) a relative exercise intensity of 60% Vo(? peak) (REL trial) at 24.8 ± 0.6°C, 26 ± 10% RH. In the FHP trial, H(prod) was similar between the HI (542 ± 38 W, 7.0 ± 0.6 W/kg or 275 ± 25 W/m2) and LO (535 ± 39 W, 6.9 ± 0.9 W/kg or 277 ± 29 W/m2) groups, while changes in rectal (T(re): HI: 0.87 ± 0.15°C, LO: 0.87 ± 0.18°C, P = 1.00) and aural canal (T(au): HI: 0.70 ± 0.12°C, LO: 0.74 ± 0.21°C, P = 0.65) temperature, whole-body sweat loss (WBSL) (HI: 434 ± 80 ml, LO: 440 ± 41 ml; P = 0.86), and steady-state local sweating (LSR(back)) (P = 0.40) were all similar despite relative exercise intensity being different (HI: 39.7 ± 4.2%, LO: 57.6 ± 8.0% Vo(2 peak); P = 0.001). At 60% Vo(2 peak), H(prod) was greater in the HI (834 ± 77 W, 10.7 ± 1.3 W/kg or 423 ± 44 W/m2) compared with LO (600 ± 90 W, 7.7 ± 1.4 W/kg or 310 ± 50 W/m2) group (all P < 0.001), as were changes in T(re) (HI: 1.43 ± 0.28°C, LO: 0.89 ± 0.19°C; P = 0.001) and T(au) (HI: 1.11 ± 0.21°C, LO: 0.66 ± 0.14°C; P < 0.001), and WBSL between 0 and 15, 15 and 30, 30 and 45, and 45 and 60 min (all P < 0.01), and LSR(back) (P = 0.02). The absolute esophageal temperature (T(es)) onset for sudomotor activity was ～0.3°C lower (P < 0.05) in the HI group, but the change in T(es) from preexercise values before sweating onset was similar between groups. Sudomotor thermosensitivity during exercise were similar in both FHP (P = 0.22) and REL (P = 0.77) trials. In conclusion, changes in core temperature and sweating during exercise in a neutral climate are determined by H(prod), mass, and BSA, not Vo(? peak).     

Blacks (african americans) have shorter free-running circadian periods than whites (caucasian americans)

The length of the free-running period (τ) affects how an animal re-entrains after phase shifts of the light-dark (LD) cycle. Those with shorter periods adapt faster to phase advances than those with longer periods, whereas those with longer periods adapt faster to phase delays than those with shorter periods. The free-running period of humans, measured in temporal isolation units and in forced desychrony protocols in which the day length is set beyond the range of entrainment, varies from about 23.5 to 26?h, depending on the individual and the experimental conditions (e.g., temporal isolation vs. forced desychrony). We studied 94 subjects free-running through an ultradian LD cycle, which was a forced desychrony with a day length of 4?h (2.5?h awake in dim light, ～35 lux, alternating with 1.5?h for sleep in darkness). Circadian phase assessments were conducted before (baseline) and after (final) three 24-h days of the ultradian LD cycle. During these assessments, saliva samples were collected every 30?min and subsequently analyzed for melatonin. The phase shift of the dim light melatonin onset (DLMO) from baseline to final phase assessment gave the free-running period. The mean?±?SD period was 24.31?±?.23?h and ranged from 23.7 to 24.9?h. Black subjects had a significantly shorter free-running period than Whites (24.18?±?.23?h, N =20 vs. 24.37?±?.22?h, N?=?55). We had a greater proportion of women than men in our Black sample, so to check the τ difference we compared the Black women to White women. Again, Black subjects had a significantly shorter free-running period (24.18?±?.23, N?=?17 vs. 24.41?±?.23, N?=?23). We did not find any sex differences in the free-running period. These findings give rise to several testable predictions: on average, Blacks should adapt quicker to eastward flights across time zones than Whites, whereas Whites should adjust quicker to westward flights than Blacks. Also, Blacks should have more difficulty adjusting to night-shift work and day sleep, which requires a phase delay. On the other hand, Whites should be more likely to have trouble adapting to the early work and school schedules imposed by society. More research is needed to confirm these results and predictions. (Author correspondence: ceastman@rush.edu ).     

Optimization of production and reaction conditions of polygalacturonase from Byssochlamys fulva

In the present study, the optimization of production and reaction conditions of polygalacturonase produced by a fungus Byssochlamys fulva MTCC 505 was achieved. The production of polygalacturonase with a considerable activity of 1.28 IU/ml was found when the culture was shaken at 30°C for 5 days in 100 ml of medium containing (w/v) 10 g/l pectin, 2 g/l NaNO?, 1 g/l KH?PO?, 0.5 g/l KCl, 0.5 g/l MgSO?. 7H?O, 0.001 g/l FeSO?. 7H?O, 0.001 g/l CaCl?. The best carbon and nitrogen source for this enzyme were pectin (1%) and Ca(NO?)? (0.1%), respectively. The enzyme gave maximum activity at incubation time of 72 h, temperature of 30°C and pH 4.5. During the optimization of reaction conditions, the enzyme showed maximum activity in sodium citrate buffer (50 mM) of pH 5.5 at 50°C reaction temperature for 15 minutes of incubation. The enzyme showed greater affinity for polygalacturonic acid as substrate (0.5%). Km and Vmax values were 0.15 mg/ml and 4.58 μmol/ml/min. The effect of various phenolics, thiols, protein inhibitors and metal ions on the enzyme activity was investigated. The enzyme was quite stable at 4°C and 30°C. At 40°C the half life of the enzyme was 6 h and at 60°C it was 2 h.     

Thermodynamics of protein self-association and unfolding. The case of apolipoprotein A-I

Protein self-association and protein unfolding are two temperature-dependent processes whose understanding is of utmost importance for the development of biological pharmaceuticals because protein association may stabilize or destabilize protein structure and function. Here we present new theoretical and experimental methods for analyzing the thermodynamics of self-association and unfolding. We used isothermal dilution calorimetry and analytical ultracentrifugation to measure protein self-association and introduced binding partition functions to analyze the cooperative association equilibria. In a second type of experiment, we monitored thermal protein unfolding with differential scanning calorimetry and circular dichroism spectroscopy and used the Zimm?Bragg theory to analyze the unfolding process. For α-helical proteins, the cooperative Zimm?Bragg theory appears to be a powerful alternative to the classical two-state model. As a model protein, we chose highly purified human recombinant apolipoprotein A-I. Self-association of Apo A-I showed a maximum at 21 °C with an association constant Ka of 5.6 × 10(5) M(?1), a cooperativity parameter σ of 0.003, and a maximal association number n of 8. The association enthalpy was linearly dependent on temperature and changed from endothermic at low temperatures to exothermic above 21 °C with a molar heat capacity ΔC(p)° of ?2.76 kJ mol(?1) K(?1). Above 45 °C, the association could no longer be measured because of the onset of unfolding. Unfolding occurred between 45 and 65 °C and was reversible and independent of protein concentration up to 160 μM. The midpoint of unfolding (T(0)) as measured by DSC was 52?53 °C; the enthalpy of unfolding (ΔH(N)(U)) was 420 kJ/mol. The molar heat capacity (Δ(N)(U)C(p)) increased by 5.0 ± 0.5 kJ mol(?1) K(?1) upon unfolding corresponding to a loss of 80?85 helical segments, which was confirmed by circular dichroism spectroscopy. Unfolding was highly cooperative with a nucleation parameter σ of 4.4 × 10(?5).     

A route for direct retinal input to the preoptic hypothalamus: dendritic projections into the optic chiasm.

With the use of Golgi, horseradish peroxidase, and electron microscopic techniques, neurons within a broad region of the preoptic hypothalamus of the mouse were shown to have dendrites that projected well into the depths of the optic chiasm. Further experimental and ultrastructural investigation demonstrated synapses between these dendrites and retinal axonal boutons within the chiasm. All synapses located in the chiasm were classified as Gray's type I. The possible function of these dendritic projections is discussed.     

Glucoprivation in the ventrolateral medulla decreases brown adipose tissue sympathetic nerve activity by decreasing the activity of neurons in raphe pallidus

In urethane/α-chloralose anesthetized rats, cold exposure increased brown adipose tissue sympathetic nerve activity (BAT SNA: +699 ± 104% control). Intravenous administration of 2-deoxy-D-glucose (2-DG; 200 mg·ml(-1)·kg(-1)) reversed the cold-evoked activation of BAT SNA (nadir: 139 ± 36% of control) and decreased BAT temperature (-1.1 ± 0.2°C), expired CO(2) (-0.4 ± 0.1%), and core temperature (-0.5 ± 0.0). Similarly, unilateral nanoinjection of the glucoprivic agent 5-thioglucose (5-TG; 12 μg/100 nl) in the ventrolateral medulla (VLM) completely reversed the cold-evoked increase in BAT SNA (nadir: 104 ± 7% of control), and decreased T(BAT) (-1.4 ± 0.3°C), expired CO(2) (-0.2 ± 0.0%), and heart rate (-35 ± 10 beats/min). The percentage of rostral raphé pallidus (RPa)-projecting neurons in the dorsal hypothalamic area/dorsomedial hypothalamus that expressed Fos in response to cold exposure (ambient temperature: 4-10°C) did not differ between saline (28 ± 6%) and 2-DG (30 ± 5%) pretreated rats, whereas the percentage of spinally projecting neurons in the RPa/raphé magnus that expressed Fos in response to cold exposure was lower in 2-DG- compared with saline-pretreated rats (22 ± 6% vs. 42 ± 5%, respectively). The increases in BAT SNA evoked by nanoinjection of bicuculline in the RPa or by transection of the neuraxis at the pontomedullary border were resistant to inhibition by glucoprivation. These results suggest that neurons within the VLM play a role in the glucoprivic inhibition of BAT SNA and metabolism, that this inhibition requires neural structures rostral to the pontomedullary border, and that this inhibition is mediated by a GABAergic input to the RPa.     

Light Exposure Among Adolescents With Delayed Sleep Phase Disorder: A Prospective Cohort Study

The objective of this study was to compare light exposure and sleep parameters between adolescents with delayed sleep phase disorder (DSPD; n?=?16, 15.3?±?1.8 yrs) and unaffected controls (n?=?22, 13.7?±?2.4 yrs) using a prospective cohort design. Participants wore wrist actigraphs with photosensors for 14 days. Mean hourly lux levels from 20:00 to 05:00?h and 05:00 to 14:00?h were examined, in addition to the 9-h intervals prior to sleep onset and after sleep offset. Sleep parameters were compared separately, and were also included as covariates within models that analyzed associations with specified light intervals. Additional covariates included group and school night status. Adolescent delayed sleep phase subjects received more evening (p?<?.02, 22:00–02:00?h) and less morning (p?<?.05, 08:00–09:00?h and 10:00–12:00?h) light than controls, but had less pre-sleep exposure with adjustments for the time of sleep onset (p?<?.03, 5–7?h prior to onset hour). No differences were identified with respect to the sleep offset interval. Increased total sleep time and later sleep offset times were associated with decreased evening (p?<?.001 and p?=?.02, respectively) and morning (p?=?.01 and p?<?.001, respectively) light exposure, and later sleep onset times were associated with increased evening exposure (p?<?.001). Increased total sleep time also correlated with increased exposure during the 9?h before sleep onset (p?=?.01), and a later sleep onset time corresponded with decreased light exposure during the same interval (p?<?.001). Outcomes persisted regardless of school night status. In conclusion, light exposure interpretation requires adjustments for sleep timing among adolescents with DSPD. Pre- and post-sleep light exposures do not appear to contribute directly to phase delays. Sensitivity to morning light may be reduced among adolescents with DSPD. (Author correspondence: auger.raymond1@mayo.edu)     

Effects of electrolytic lesion of hypothalamic paraventricular nucleus and its related areas on the sleep waking cycle in the cat

In order to study putative hypothalamic mechanisms of sleep waking cycle regulation we destroyed, by electrolytic coagulation, a large part of the medial hypothalamus overlapping the paraventricular nucleus in 6 adult cats. We never observed any modification of light slow wave sleep. Three of the six cats presented no paradoxical sleep (PS) impairment, despite an almost total destruction of neurophysin-immunoreactive cells of PVN in two cats and marked signs of diabetes insipidus in the third. Further, in the other three animals a statistically significant decrease of daily quantities of PS and deep slow wave sleep (SWS2) were related to an extensive destruction of the anterior hypothalamic area. These results suggest lack of influence of the PVN in sleep regulation and an involvement of the anterior hypothalamus in the onset of SWS2 and PS.     

From the subarctic to the tropics: effects of 4-month deployment on soldiers' heat stress, heat strain, and physical performance

The aim of the study was to evaluate the heat stress of Finnish male soldiers (N = 20, age 22.0 ± 2.5 years, body mass 78.8 ± 11.5 kg, and height 180.2 ± 5.6 cm) during their 4-month deployment in a hot environment and to find out the effects on physical performance and body composition. The troops moved from 2.5° C (mean monthly temperature) in Finland to 31.9° C in Chad. During the deployment, temperatures varied between 13.5 and 57.0° C outdoors and in the vehicles and tents. During 1-day recording in the middle of the deployment, skin temperatures were 34-35° C during daytime and maximal core temperature remained mainly below 38.0° C. Body mass decreased (78.4 ± 11.5 kg vs. 75.6 ± 8.6, p = 0.007) during the deployment without changes in fat mass. The sit-up performance increased by 10.9% (46 ± 10 reps·min?1 vs. 51 ± 7 reps·min?1, p < 0.01), and the maximal force production of the leg extensor muscles increased (3,042 ± 614 N vs. 3,277 ± 706 N, p < 0.05) without change in the rate of force development. No changes were observed in the push-ups, repeated squats, maximal grip strength, and running distance during the 12-minute test. In conclusion, the soldiers were able to maintain or improve their physical performance during the deployment despite the heat stress. It is important to encourage soldiers to engage in physical training, especially during a thermally appropriate time of the day or in air-conditioned facilities. Monitoring of local heat stress is also recommended.     

The onset temperature of the heat-shock response and whole-organism thermal tolerance are tightly correlated in both laboratory-acclimated and field-acclimatized tidepool sculpins (Oligocottus maculosus)

We examined the relationship between thermal tolerance, measured as critical thermal maximum (CT(max)), and aspects of the heat-shock response in tidepool sculpins (Oligocottus maculosus) acclimated to constant laboratory temperatures or acclimatized to field conditions. The CT(max) of fish laboratory acclimated to 6°, 13°, and 20°C were 27.6° ± 0.1°C, 29.5° ± 0.1°C, and 30.8° ± 0.1°C, respectively, increasing linearly by 0.2°C for each 1°C increase in acclimation temperature. The CT(max) of field-acclimatized fish from the low intertidal (29.9° ± 0.1°C) was significantly lower than that of fish from the mid- (30.5° ± 0.1°C) and high (30.4° ± 0.1°C) intertidal. CT(max) and the onset temperature of hsp70 induction in gill (T(on)) were highly correlated in both laboratory-acclimated and field-acclimatized sculpins, with T(on) occurring at 2°C below CT(max) in all cases. However, there was no consistent relationship between CT(max) and the maximum levels of gill hsp70 mRNA. Predicted "acclimation" temperature (15.9° ± 0.3°C) and mean habitat temperature (15.9° ± 1.6°C) were similar for sculpins from low intertidal pools, but this relationship was not apparent in mid- and high intertidal fish. Mark-recapture experiments indicated that approximately 80% of fish from low intertidal pools were residents of that pool, but residency rates were less than 50% in mid- and high intertidal pools, which may explain the lack of correlation between CT(max) and habitat variables in these groups. These data indicate that gill hsp70 T(on) and CT(max) are highly correlated indicators of the thermal performance of tidepool sculpins in both laboratory and field settings.     

PHASE RELATIONSHIP BETWEEN SKIN TEMPERATURE AND SLEEP-WAKE RHYTHMS IN WOMEN WITH VASCULAR DYSREGULATION AND CONTROLS UNDER REAL-LIFE CONDITIONS

The aim of the study was to investigate whether women with primary vascular dysregulation (VD; main symptoms of thermal discomfort with cold extremities) and difficulties initiating sleep (DIS) exhibit a disturbed phase of entrainment (Ψ) under everyday life conditions. The authors predicted a phase delay of the distal-proximal skin temperature gradient and salivary melatonin rhythms with respect to the sleep-wake cycle in women with VD and DIS (WVD) compared to controls (CON), similar to that found in their previous constant-routine laboratory data. A total of 41 young healthy women, 20 with WVD and 21 matched CON without VD and normal sleep onset latency (SOL), were investigated under ambulatory conditions (following their habitual bedtimes) during 7 days of continuous recording of skin temperatures, sleep-wake cycles monitored by actimetry and sleep-wake diaries, and single evening saliva collections for determining the circadian marker of dim light melatonin onset (DLMO). Compared to CON, WVD showed increased distal vasoconstriction at midday and in the evening, as indicated by lower distal (DIST; hands and feet) and foot-calf skin temperatures, and distal-proximal skin temperature gradients (p?<?.05). WVD manifested distal vasoconstriction before lights-off that also lasted longer after lights-off than in CON. In parallel, WVD exhibited a longer SOL (p?<?.05). To define internal phase-relationships, cross-correlation analyses were performed using diurnal rhythms of wrist activity and foot skin temperature. WVD showed a phase delay in foot skin temperature (CON versus WVD: 3.57?±?17.28?min versus 38.50?±?16.65?min; p?<?.05) but not in wrist activity. This finding was validated by additional within-subject cross-correlation analyses using the diurnal wrist activity pattern as reference. DLMO and habitual sleep times did not differ between CON and WVD. The authors conclude that WVD exhibit a phase delay of distal vasodilatation with respect to their habitual sleep-wake cycle and other circadian phase markers, such as DLMO. A full factorial design will have to show whether the finding is specific to primary vascular dysregualtion, to DIS, or to their interaction. (Author correspondence: Kurt.kraeuchi@upkbs.ch)     

Chronotherapy with valsartan/hydrochlorothiazide combination in essential hypertension: improved sleep-time blood pressure control with bedtime dosing

Administration of angiotensin receptor blockers at bedtime results in greater reduction of nighttime blood pressure than dosing upon awakening, independent of the terminal half-life of each individual medication. To obtain blood pressure (BP) target goals most patients require treatment with more than one hypertension medication. However, the potential differing effects on BP regulation of combination therapy depending on the time-of-day of administration have scarcely been investigated. Accordingly, the authors prospectively evaluated the administration-time-dependent BP-lowering efficacy of valsartan/hydrochlorothiazide (HCTZ) combination therapy. The authors conducted a randomized, open-label, blinded-endpoint trial on 204 subjects with essential hypertension (95 men/109 women), 49.7?±?11.1 (mean?±?SD) yrs of age. The BP of participants in this trial was not properly controlled with respect to published ambulatory BP criteria after initially randomized to valsartan monotherapy (160?mg/day), whether routinely ingested upon awakening by one group or at bedtime by another group for 12 wks. Thus, HCTZ (12.5?mg/day) was added to valsartan as a single-pill formulation, maintaining the original treatment-time, i.e., upon awakening or at bedtime, of participants of the two groups, for another 12 wks. BP was measured by ambulatory monitoring for 48?h at inclusion and after each 12-wk span of therapy. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately define the beginning and end of daytime activity and nocturnal sleep so that the respective BP means for every participant at each evaluation could be precisely determined. Combination therapy resulted in a similar statistically significant reduction of the 48-h BP mean from baseline for both treatment-time groups (17.0/11.5?mm Hg in systolic/diastolic BP after combination therapy on awakening; 17.9/12.1?mm Hg reduction after combination treatment at bedtime; p?>?.542 between groups). The awake BP mean was reduced to a comparable extent in both treatment-time groups (p?>?.682). However, bedtime compared to morning dosing better reduced the asleep means of systolic BP (20.1 vs. 16.0?mm Hg; p?=?.015) and pulse pressure (6.5 vs. 4.0?mm Hg; p?=?.007 between groups). Accordingly, the proportion of subjects with a baseline non-dipper BP profile was significantly reduced from 59% to 23% only after bedtime combination treatment (p?相似文献