Sleep patterns during 20-m nitrox saturation dives

The sleep patterns were examined through three simulated 20-m nitrox saturation dives. The standard polysomnography of 12 divers was recorded respectively for a total of 204 nights, as were patterns of change or consistency in sleep variables. For the 11 divers in their 20s and 30s there was nothing unusual about their sleep variables. However, a reduction of total sleep time in accordance with the lengthening of sleep latency was observed. This was recognized from the latter part of the bottom period to the postdive period. This tendency was notable for the diver in his 50s. These findings suggest that the decompression environment and the psychological stress of the long-term closed environment of a hyperbaric chamber have effects on divers' sleep.     

Sleep patterns during 30-m nitrox simulated saturation dives.

The sleep patterns were examined during the simulated 30-m nitrox saturation dives. The standard polysomnography of 15 divers was recorded for a total of 255 nights, as were patterns of change or consistency in sleep variables. A reduction of total sleep time in accordance with the lengthening of sleep latency and the wake after sleep onset was observed through the latter part of the bottom period to the post-dive period, but the other sleep variables did not show any changes. These findings suggest that decompression and the psychological stress due to being in the closed environment of a hyperbaric chamber for a long time have effects on divers' sleep.     

Sleep patterns during 30-m nitrox saturation dives and in a confined atmospheric environment

Sleep patterns during saturation dives equivalent to a 30-m depth (pressurized condition) and habitation in a confined environment at 1 atm absolute pressure (non-pressurized condition) were studied to determine the effects of environmental pressure. Eight inexperienced divers experienced the pressurized condition of the saturation dives, and nine healthy subjects experienced the non-pressurized condition. Standard polysomnographs were recorded for 262 nights. For both conditions, reductions in total sleep time accompanied by lengthening in sleep latency and reduction in sleep efficiency were observed from the latter part of the experiments through to the recovery periods. These findings suggest that changes were related to psychological and physiological stresses caused by long stays in a confined environment and not by the environmental pressure.     

Vitamin B12 treatment for delayed sleep phase syndrome: A multi-center double-blind study

Abstract  The active form of vitamin B₁₂ (methylcobalamin) has been reported to be effective on sleep-wake rhythm disorders. Previous studies, however, were performed under open trial, and the effect of vitamin B₁₂ has not been properly evaluated. The aim of this double-blind study was to investigate the efficacy of methylcobalamin on delayed sleep phase syndrome (DSPS). Methylcobalamin (3 mg/day) or placebo was administered for 4 weeks. The subjects were 50 patients with DSPS aged 13–55 years (26.8 ± 1.3), 27 of whom received the active drug while 23 received the placebo. No significant differences were observed between the 2 groups in subjective evaluations of mood or drowsiness during the daytime or in night sleep by sleep-log evaluation. These results indicate that 3 mg methylcobalamin administered over 4 weeks is not an effective treatment for DSPS.     

Downregulated hypothalamic 5-HT3 receptor expression and enhanced 5-HT3 receptor antagonist-mediated improvement in fatigue-like behaviour in cholestatic rats

Abstract  The serotonin neurotransmitter system, including the 5-HT₃ receptor, has been implicated in the genesis of fatigue in patients with liver disease. Therefore, we examined the possible role of 5-HT₃ receptors in cholestasis-associated fatigue. Rats were either bile duct resected (BDR) or sham resected and studied 10 days postsurgery. A significant decrease in hypothalamic 5-HT₃ receptor expression was detected by immunohistochemistry and Western blot in BDR vs sham rats, coupled with increased hypothalamic serotonin turnover identified by an elevated 5-hydroxyindoleacetic acid (5-HIAA) to 5-HT ratio in BDR vs sham rats. To examine fatigue-like behaviour, an activity meter was used. BDR rats exhibited significantly lower locomotor activity than did sham animals. Subcutaneous injection of the 5-HT₃ receptor antagonist tropisetron (0.1 mg kg⁻¹) resulted in significantly increased locomotor activity in BDR rats compared to the activity in saline-treated controls, but was without effect in sham rats. However, a 10-fold higher dose of tropisetron significantly increased locomotor activity in both BDR and sham rats compared to saline-injected controls. These findings indicate that cholestasis in the rat is associated with increased hypothalamic serotonin turnover, decreased hypothalamic 5-HT₃ receptor expression, and enhanced sensitivity to locomotor activation induced by 5-HT₃ receptor antagonism, thereby implicating the 5-HT₃ receptor system in cholestasis associated fatigue.     

Circadian and Estral Changes in the Hypothalamic Prostaglandin E2 Content and [3H]Prostaglandin E2 Binding in Female Rats

Prostaglandin E₂, (PGE₂) is involved in the luteinizing hormone-releasing hormone-stimulated luteinizing hormone surge in female rats and may act via specific membrane receptors. The following studies were performed to determine whether there were any changes in the hypothalamic PGE₂ binding and/or PGE₂ content which were specific to proestrus and not to the rest of the estrous cycle. Groups of female Wistar rats were sacrificed at 3-h intervals throughout the estrous cycle to determine both the circadian and circaestral changes in the hypothalamic PGE₂ content and [³H]PGE₂ binding. The hypothalamic PGE₂ content was maximal at 1700 h on each of the 4 consecutive days of the estrous cycle but was independent of the stage of the cycle. [³H]PGE₂ binding also displayed a circadian rhythm; the lowest binding occurred near the circadian peak of PGE₂, suggesting that the PGE₂ binding sites were occupied by endogenous PGE₂. Since such circadian rhythms were not observed in the hypothalamus of male rats, they may be under the control of ovarian steroids. Also, since PGE₂ binding and the PGE₂ content both exhibit a diurnal pattern independent of the day of the cycle, there may be changes in the PGE₂ receptor-mediated process coupled to an adenylyl cyclase which could explain the luteinizing hormone surge in proestrus.     

A polysomnographic study of sleep patterns in normal humans with low- or high-anxiety personality traits

To clarify the effects of anxiety-related personality traits on sleep patterns, polysomnographic examinations (PSG) were performed over 4 consecutive nights on normal humans who tested within the low- or high-anxiety ranges. The subjects consisted of two groups of six male university students who scored either less than 45 points (low-anxiety group) or more than 55 points (high-anxiety group) on the Spielberger's State Trait Anxiety Inventory. Compared to the levels of sleep change in the high-anxiety group, the low-anxiety group exhibited a greater change in REM sleep and stage 2 sleep. The REM sleep in the low-anxiety group was shorter on the first and second nights compared to the third and fourth nights, and the stage 2 sleep was longer on the first night than on the remaining three nights. Thus, the low-anxiety group showed a first-night effect followed by partial recovery on the second night, while the high-anxiety group exhibited no obvious first-night effect. These results suggest that there is a difference in sleep patterns, assessed by consecutive PSG, between those with low- and high-anxiety traits, and that anxiety-related personality traits attenuate the occurrence of the first-night effect, reflecting a lower adaptability to a novel environment.     

Leukotrienes B4 and C4 in MS

Release of leukotriene B4 (LTB4) and leukotriene C4 (LTC4) from neutrophils and platelet-neutrophil suspensions in response to ionophore A23187 was measured in 12 multiple sclerosis (MS) patients and 8 healthy volunteers. LTC4 release from neutrophils, as well as from platelet-neutrophil suspensions, was significantly decreased in MS patients compared with the controls. There was no significant difference in the release of LTB4 between MS patients and controls. The findings suggest that permanent stimulation of platelets and neutrophils e.g., by encephalitogenic peptide leads to continuous LTC4 release with subsequent depletion of intracellular substrates serving as precursors for the formation of 5-lipoxygenase products. Since the target of microvascular actions of LTC4 are postcapillary venules, the release of this sulfidopeptide leukotriene might play a pathogenetic role in the formation of MS lesions.     

Metabolism of vitamin D2 and vitamin D3 in patients on anticonvulsant therapy

We examined the effect of short-term treatment with pharmacological doses of vitamin D2 or vitamin D3 on the serum concentration of 1,25(OH)2D metabolites in epileptic patients on chronic anticonvulsant drug therapy. Nine patients were studied before and after treatment with vitamin D2 4000 IU daily for 24 weeks and 10 before and after treatment with vitamin D3 in the same dose. Before treatment the serum concentrations of 1,25(OH)2D and 25(OH)D were significantly lower in epileptics than in normal subjects (P less than 0.01). Vitamin D2 treatment increased the serum concentration of 1,25(OH)2D2, but a corresponding decrease in 1,25(OH)2D3 resulted in an unchanged serum concentration of total 1,25(OH)2D. The serum concentration of 25(OH)D2 and 25(OH)D increased significantly, whereas there was a small decrease in 25(OH)D3. Vitamin D3 treatment did not change the serum concentration of 1,25(OH)2D3 whereas serum 25(OH)D3 increased significantly. The correlation between the serum ratio of 1,25(OH)2D2/1,25(OH)2D3 and 25(OH)D2/25(OH)D3 estimated on vitamin D2-treated epileptic patients and normal subjects was highly significant (P less than 0.01). The data indicate that the serum concentration of 1,25(OH)2D2 and 1,25(OH)2D3 are directly proportional to the amount of their precursors 25(OH)D2 and 25(OH)D3 and that the concentration of total 1,25(OH)2D is tightly regulated.     

Divergent role for CRF1 and CRF2 receptors in the modulation of visceral pain

Both anti- and pro-nociceptive effects of corticotropin-releasing factor (CRF) treatment on visceral pain have been reported. Here, this dual action of CRF was differentiated by selective (in)activation of the CRF1 and CRF2 receptor prior to a visceral pain stimulus. Visceral pain was evaluated out of behavioural and visceromotor (abdominal electromyogram) responses to duodenal distension in the freely moving rat. Intraperitoneal (i.p.) CRF (50 microg kg-1) increased the distension-induced visceromotor and behavioural pain response. The pro-nociceptive effects of CRF on the behavioural response were attenuated by a selective CRF1 (CP-154526; 20 mg kg-1) but not a selective CRF2 [antiSauvagine30 (aSVG30); 100 microg kg-1] antagonist. Selective activation of the CRF2 receptor by stresscopin-related peptide (SRP; i.p. 25 microg kg-1) reduced the distension-induced visceromotor and behavioural response. Intrathecal injection of CRF (2 microg 10 microL-1) or SRP (20 microg 10 microL-1) decreased the distension-induced visceromotor and behavioural response. The antinociceptive effects of intrathecal CRF on the behavioural response were attenuated by aSVG30 (20 microg 10 microL-1) but not with CP-154526 (10 microg 10 microL-1). These findings indicate that the CRF1 receptor is involved in pro-nociception of visceral pain, whereas the CRF2 receptor is mainly involved in antinociception. This divergent role of the CRF subreceptors may explain the bimodal effects of CRF treatment on visceral nociception.     

Effect of vitamin D2 and D3 on bone-mineral content in carbamazepine-treated epileptic patients

ABSTRACT In order to clarify whether carbamazepine causes disturbances in calcium and bone metabolism we examined the effect of vitamin D₂ or D₃ in 30 epileptic outpatients. They had been treated for at least 1 year with carbamazepine given as monotherapy. The local bone mineral in the forearms and the total bone mineral was measured before and during treatment with the vitamins (4000 IU/day) for 24 weeks. The bone mineral was not significantly different from controls before the study and it remained unchanged in both treatment groups during the study periods. Similarly, the biochemical indices of bone metabolism were virtually unchanged during the treatment period. We, thus, conclude that epileptic patients on carbamazepine monotherapy have normal bone metabolism.     

Different metabolism of vitamin D2 and vitamin D3 in epileptic patients on carbamazepine

Serum concentrations of vitamin D metabolites were measured in 30 epileptic outpatients on monotherapy with carbamazepine before and during treatment with either vitamin D2 or vitamin D3, 4000 IU per day for 24 weeks. Vitamin D2 treatment increased the serum concentration of 25OHD2, but a corresponding decrease in 25OHD3 resulted in an unchanged serum value of total 25OHD. Vitamin D3 treatment increased the serum concentration of 25OHD3. The resulting serum level of 25OHD was consequently twice the level of that in the D2-treated group. The serum concentrations of the dihydroxy metabolites showed a similar difference between the 2 treatment groups. We conclude that treatment with vitamins D2 and D3 in the same doses produces considerably different serum concentrations of vitamin D metabolites. If the present findings can be extrapolated to normal subjects, it is important to consider more carefully which D-vitamin should be used, both with regard to therapy and supplementation.     

Impact of pediatric epilepsy on sleep patterns and behaviors in children and parents

Purpose: Disrupted sleep patterns in children with epilepsy and their parents are commonly described clinically. A number of studies have shown increased frequency of sleep disorders among pediatric epilepsy patients; however, few have characterized the association between epilepsy and parental sleep quality and household sleeping arrangements. The purpose of this study was to explore the effect of pediatric epilepsy on child sleep, parental sleep and fatigue, and parent‐child sleeping arrangements, including room sharing and cosleeping. Methods: Parents of children 2 to 10 years of age with and without epilepsy completed written questionnaires assessing seizure history, child and parent sleep, and household sleeping arrangements. Children’s Sleep Habits Questionnaire (CSHQ) scores were used to evaluate sleep disturbances for the child. The Pittsburgh Sleep Quality Index (PSQI) and the Iowa Fatigue Scale (IFS) were used to evaluate parental sleep and fatigue, respectively. The Early Childhood Epilepsy Severity Scale (E‐Chess) was used to assess epilepsy severity. Key Findings: One hundred five households with a child with epilepsy and 79 controls participated in this study. Households with a child with epilepsy reported increased rates of both parent–child room sharing (p < 0.001) and cosleeping (p = 0.005) compared to controls. Children with epilepsy were found to have greater sleep disturbance by total CSHQ score (p < 0.001) and the following subscores: parasomnias (p < 0.001), night wakings (p < 0.001), sleep duration (p < 0.001), daytime sleepiness (<0.001), sleep onset delay (p = 0.009), and bedtime resistance (p = 0.023). Parents of children with epilepsy had increased sleep dysfunction (p = 0.005) and were more fatigued (p < 0.001). Severity of epilepsy correlated positively with degree of child sleep dysfunction (0.192, p = 0.049), parental sleep dysfunction (0.273, p = 0.005), and parental fatigue (0.324, p = 0.001). Antiepileptic drug polytherapy was predictive of greater childhood sleep disturbances. Nocturnal seizures were associated with parental sleep problems, whereas room sharing and cosleeping behavior were associated with child sleep problems. Within the epilepsy cohort, 69% of parents felt concerned about night seizures and 44% reported feeling rested rarely or never. Finally, 62% of parents described decreased sleep quality and/or quantity with cosleeping. Significance: Pediatric epilepsy can significantly affect sleep patterns for both the affected child and his or her parents. Parents frequently room share or cosleep with their child, adaptations which may have detrimental effects for many households. Clinicians must not only be attentive to the sleep issues occurring in pediatric patients with epilepsy, but also for the household as a whole. These data provide evidence of a profound clinical need for improved epilepsy therapeutics and the development of nocturnal seizure monitoring technologies.     

Potentiated cAMP Rise in Metabotropically Stimulated Rat Cultured Astrocytes by a Ca2+-related Al/k2 Adenosine Receptor Cooperation

Adenosine agonists favoured an intracellular Ca²⁺ rise in cultured type 1 astrocytes if the metabotropic glutamate receptors were concomitantly stimulated by (2S,1′s, 2′s)-2-(carboxycyclopropyl) glycine (l -CCG-I; group II agonist), quisqualate (group I agonist) or 1 -aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD; group VII agonist). Since the generation of a Ca²⁺ signal reflected a newly adopted adenosine A₁ receptor action, we tested the possible consequence that the established opposing control of the cellular cAMP content by inhibitory A₁ and stimulatory A₂ receptor activation was also altered. During metabotropic receptor stimulation by L-CCG-I, quisqualate or t-ACPD, the non-selective adenosine agonist 2-chloroadenosine (CI-adenosine) caused a potentiated cAMP increase which markedly exceeded that produced by CI-adenosine alone. This cAMP potentiation resulted from altered and Ca²⁺-dependent A₁/A₂ receptor cooperation. It was abolished by A₁ receptor blockade and could not be achieved in the presence of t-ACPD by the A₁ agonist R(-)N⁶-(2-phenylisopropyl)-adenosine or by the A₂ agonist 5′-N-ethyl carboxyamidoadenosine alone, but was obtained using their combination. The cAMP potentiation was blocked by intracellular Ca²⁺ chelation and the required A₁ receptor action could be mimicked by a Ca²⁺ signal generated by the P_2y receptor agonist adenosine 5β-(β-thio) diphosphate. The results support the conclusion that nanomolar concentrations of adenosine may influence astrocyte reactions by stimulating the Ca²⁺ and cAMP-dependent signalling cascade.     

Critical Role for M3 Muscarinic Receptors in Paradoxical Sleep Generation in the Cat

In the cat, microdialysis application of 200 μM carbachol to the peri-locus coeruleus a (peri-LCα) of the mediodorsal pontine tegmentum produced a marked (≤5–fold) increase in paradoxical sleep. This effect was blocked by 5–50 μM 4–diphenylacetoxy-N-methylpiperidine methiodide (4–DAMP), an M₁/M₃-selective muscarinic receptor antagonist. In contrast, the effect was not reversed by methoctramine, an M₂-selective antagonist, or pirenzepine, an M₁-selective antagonist, even at concentrations as high as 500 μM. In addition, unilateral application of 5 μM 4–DAMP alone to the peri-LCa induced both a >60% decrease in paradoxical sleep and a state of paradoxical sleep without atonia, whereas 50 μM pirenzepine and 500 μM methoctramine had no effect. Our findings are further evidence for the important role played by the peri-LCα and demonstrate a critical role for M₃ muscarinic cholinergic receptors in the generation of paradoxical sleep.     

Changes in serotonin in rat brain during slow-wave sleep and paradoxical sleep: application of the microwave fixation method to sleep research

Neural responses to several chemicals of the pit organs and terminal buds on the facial skin of the carp were compared electrophysiologically. Nerve inpulses from the pit organs were larger than those from the terminal buds. The pit organs were more sensitive to salts and especially acids than the terminal buds. The former did not respond to sucrose, silk worm pupa extract, betaine and amino acids except acidic ones. The latter, however, responded well to them.