European malaria vaccine initiative.
Explore the source record for details and available documents.
Africa↗
Biomedical subjects
B Bjorvatn
Publications and source records attributed to B Bjorvatn.
Bright light treatment used for adaptation to night work and re-adaptation back to day life. A field study at an oil platform in the North Sea.
Night workers complain of sleepiness, reduced performance and disturbed sleep due to lack of adjustment of the circadian rhythm. In simulated night-work experiments scheduled exposure to bright light has been shown to reduce these complaints. Here we studied the effects of bright light treatment on the adaptation to 14 days of consecutive night work at an oil platform in the North Sea, and the subsequent readaptation to day life at home, using the Karolinska sleep/wake diary. Bright light treatment of 30 min per exposure was applied during the first 4 nights of the night-shift period and the first 4 days at home following the shift period. The bright light exposure was scheduled individually to phase delay the circadian rhythm. Bright light treatment modestly facilitated the subjective adaptation to night work, but the positive effect of bright light was especially pronounced during the re-adaptation back to day life following the return home. Sleepiness was reduced and the quality of day was rated better after exposure to bright light. The modest effect of bright light at the platform was, possibly, related to the finding that the workers seemed to adapt to night work within a few days even without bright light. These results suggest that short-term bright light treatment may help the adaptation to an extended night-work period, and especially the subsequent re-adaptation to day life.
Adaptation, Physiological↗
The 5-HT1A receptor antagonist p-MPPI blocks 5-HT1A autoreceptors and increases dorsal raphe unit activity in awake cats.
The effects of the putative 5-HT1A receptor antagonist 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzam ide (p-MPPI) were examined on the activity of serotonergic dorsal raphe nucleus neurons in freely moving cats. Systemic administration of p-MPPI produced a dose-dependent increase in firing rate. This stimulatory effect of p-MPPI was evident during wakefulness (when serotonergic neurons display a relatively high level of activity), but not during sleep (when serotonergic neurons display little or no spontaneous activity). p-MPPI also blocked the ability of the 5-HT1A receptor agonist 8-hydroxy-(2-di-n-propylamino)tetralin (8-OH-DPAT) to inhibit serotonergic neuronal activity. This antagonism was evident both as a reversal of the neuronal inhibition produced by prior injection of 8-OH-DPAT and as a shift in the potency of 8-OH-DPAT following p-MPPI pretreatment. Overall, these results in behaving animals indicate that p-MPPI acts as an effective 5-HT1A autoreceptor antagonist. The increase in firing rate produced by p-MPPI supports the hypothesis that autoreceptor-mediated feedback inhibition operates under physiological conditions.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
EEG power densities (0.5-20 Hz) in different sleep-wake stages in rats.
Frontofrontal and frontoparietal EEG power densities (0.5-20 Hz) in waking, light and deep slow-wave sleep, transition-type sleep, and rapid-eye-movement (REM) sleep were investigated for 8 h during the light period in 16 male Wistar rats. The data indicate that as delta activity (0.5-4.5 Hz) increased from light to deep slow-wave sleep, the number of epochs per scoring epoch with high sigma activity (11-16 Hz) as well as power densities in the rest of the spectrum (5-20 Hz) including sigma frequencies also increased. This is in parallel with other rat studies but contrasts findings in humans, where EEG sigma activity is reported to decrease as sleep deepens. During the 8-h recording period, delta activity decreased whereas sigma activity increased.
Animals↗
On-line detection of extracellular levels of serotonin in dorsal raphe nucleus and frontal cortex over the sleep/wake cycle in the freely moving rat.
We used in vivo microdialysis coupled with polygraphic recording to monitor 5-hydroxytryptamine levels in the dorsal raphe nucleus and frontal cortex across waking, slow-wave sleep and rapid eye-movement sleep. Male Sprague-Dawley rats were prepared with electroencephalogram and electromyogram electrodes. Microdialysis probes were placed in dorsal raphe nucleus and/or frontal cortex. Dialysate samples were manually collected during polygraphically-defined behavioural states and the level of serotonin was assayed by means of microbore high-performance liquid chromatography separation and electrochemical detection. Samples from microdialysis probes histologically localized to the dorsal raphe nucleus and frontal cortex showed different levels of extracellular 5-hydroxytryptamine in waking, slow-wave sleep and rapid eye-movement sleep. In dorsal raphe nucleus the extracellular level of serotonin was highest in waking, decreased in slow-wave sleep to 69% and in rapid eye-movement sleep to 39% of waking mean level (waking 3.2 +/- 0.9; slow-wave sleep 2.2 +/- 0.8; rapid eye-movement sleep 1.3 +/- 0.4 fmol/sample). Mean extracellular levels of serotonin in frontal cortex displayed a similar pattern (waking 1.7 +/- 0.4; slow-wave sleep 1.0 +/- 0.3; rapid eye-movement 0.5 +/- 0.05 fmol/sample). In frontal cortex, rapid eye-movement sleep samples were only obtained in three animals. Our findings are consistent with previous results in cats, and suggest that in rats also, extracellular 5-hydroxytryptamine levels in dorsal raphe nucleus and frontal cortex across the sleep/wake cycle might reflect serotonergic neuronal activity. The findings stress the importance of controlling for behavioural state when investigating neurochemical correlates of serotonergic function.
Animals↗
Rapid adaptation to night work at an oil platform, but slow readaptation after returning home.
Previous research indicates that night workers' circadian rhythms do not adapt to night work and that disturbed sleep and wakefulness persist, even after weeks of working on night shift. We studied adjustment to 14 days of consecutive night work at an oil platform and the readjustment to day life at home, using the Karolinska sleep/wake diary. The platform workers adapted to night work within a few days, as indicated by the rapid reduction of night-work sleepiness, and by the gradual delay of bedtime to an hour commensurate with the behavior of day workers. Readaptation to day life was slower and more difficult, adding evidence of a complete adaptation to night work. We conclude that the lack of conflicting exposure to daylight in the morning may have facilitated the rapid adjustment to night work.
Adaptation, Physiological↗
Changes in sleep and wakefulness following 5-HT1A ligands given systemically and locally in different brain regions.
Serotonin (5-HT) has been implicated in the regulation of vigilance, but whether 5-HT is important for sleep or waking processes remains controversial. This review addresses the role of 5-HT1A receptors in sleep and wakefulness. Systemic administration of 5-HT1A agonists consistently increases wakefulness, whereas slow wave sleep (SWS) and REM (rapid-eye movement) sleep are reduced. However, systemic 5-HT1A agonists also produce a delayed increase in deep slow wave sleep, or an increase in slow wave activity. Intrathecal administration of a selective 5-HT1A agonist produces an increase in SWS, whereas wakefulness is reduced, presumably by stimulating 5-HT1A receptors located presynaptically on primary afferents in the spinal cord. Microinjection of serotonin into the region of the cholinergic basalis neurons produces an increase in slow wave activity, presumably by stimulating 5-HT1A receptors. Microdialysis perfusion of a selective 5-HT1A agonist into the dorsal Raphe nucleus causes an increase in REM sleep, whereas the other sleep/wake stages are unaltered. The REM sleep increase is likely due to a decrease in 5-HT neuronal activity, and thereby reduced 5-HT neurotransmission in projection areas, e.g. the laterodorsal and pedunculopontine tegmental nuclei. Direct injection of a selective 5-HT1A agonist into the pedunculopontine tegmental nuclei reduces REM sleep, consistent with such a hypothesis. These complex sleep/wake data of 5-HT1A ligands suggest that 5-HT1A receptor activation may increase waking, increase slow wave sleep or increase REM sleep depending on where the 5-HT1A receptors are located within the central nervous system.
Brain↗
Sleep-wake and eeg effects following adenosine a1 agonism and antagonism: similarities and interactions with sleep-wake and eeg effects following a serotonin reuptake inhibitor in rats.
Adenosine is currently being investigated as a possible mediator of a homeostatic sleep need. Reports from different laboratories suggest that both adenosine A1 agonists and selective serotonin reuptake inhibitors (SSRI) increase deep slow wave sleep (SWS-2) after an interval. In this study, the sleep-wake effects of the adenosine A1 agonist N6-cyclopentyladenosine (CPA) and the SSRI zimeldine are directly compared in the same animals. Since the SWS-2 increase following SSRIs may be secondary to increased adenosine levels during the initially increased waking, it was also investigated whether the adenosine A1 antagonist 8-cyclopentyltheofylline (CPT) would inhibit the SWS-2 increase following the serotonin reuptake inhibitor. Both the adenosine A1 agonist CPA and the SSRI zimeldine increased SWS-2 after an interval. Both drugs increased slow wave activity and decreased 9-20 Hz activity during SWS-2. Both the adenosine A1 antagonist CPT, zimeldine and the two drugs combined initially increased waking and subsequently increased SWS-2 after 2 or 4 h. All treatments increased 2-6 Hz activity in SWS-2 after 2h. Thus, CPT did not antagonize the SWS-2 increase of zimeldine. Based on the sleep and power spectral effects it is suggested that the adenosine A1 antagonist potentiated the zimeldine effect, possibly due to antagonism of adenosine A1 inhibition of serotonin release. The data indicate that the delayed SWS-2 and slow wave activity increases following zimeldine are not due to increased stimulation of adenosine A1 receptors following the initial sleep loss.
Analysis of Variance↗
Sleep/waking effects of a selective 5-HT1A receptor agonist given systemically as well as perfused in the dorsal raphe nucleus in rats.
Sleep/waking stages and behavior were studied following the selective 5-HT1A agonist 8-OH-DPAT given subcutaneously (s.c.) (0.010-0.375 mg/kg) as well as perfused continuously (10 microM) for 6 h into the dorsal raphe nucleus (DRN) using microdialysis. Given systemically, 8-OH-DPAT at 0.375 mg/kg s.c. induced 5-HT behavioral syndrome, increased waking to 149% and reduced slow wave sleep (SWS) to 86%, transition to 76% and rapid eye movement (REM) sleep to 73%. The effect on deep SWS (SWS-2) was biphasic, with an increase after 2 h. 8-OH-DPAT at 0.010 mg/kg did not have any vigilance effects. 8-OH-DPAT perfusion in DRN produced a fourfold increase in REM sleep compared to perfusion of artificial cerebrospinal fluid. This is consistent with the hypothesis that reduced 5-HT neurotransmission following 5-HT1A autoreceptor stimulation will disinhibit cholinergic REM-promoting mesopontine neurons and thereby lead to a REM sleep increase. The other sleep/waking stages were not significantly affected by 8-OH-DPAT perfusion in DRN.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
[Phototherapy. An alternative for seasonal affective disorders or sleep disorders].
Although clinicians have observed for centuries that som depressed patients become worse in the winter, it was first in 1984 that Norman Rosenthal and co-workers described a syndrome which they called seasonal affective disorder (SAD), characterised by winter depression, lethargy and a craving for carbohydrate. Phototherapy was proved to be an effective treatment right from the start. Recently it has been reported that not only depression, but also panic disorder and obsessive compulsive disorders may exhibit a seasonal pattern and thus benefit from phototherapy. Phototherapy may also benefit patients suffering from "sun-downing", a syndrome of confusion and agitation in the evening in persons with Alzheimer's disease. Based on the observation that bright light may both elevate brain serotonin and ameliorate sleep abnormalities, the authors report the results of phototherapy for treatment of non-seasonal depressions, either alone or in combination with antidepressants or sleep deprivation.
Alzheimer Disease↗
[Phototherapy of jet lag, night work and sleep disorders].
Jet lag, complaints associated with night work, and certain sleep disorders may be caused by misalignment between the endogenous circadian rhythm and the sleep/wake cycle. The authors discuss how light influences and regulates the circadian rhythm. The endogenous circadian rhythm is generated by the suprachiasmatic nucleus, and the effect of light is mediated to this nucleus directly via the retinohypothalamic tract. The effect is dependent on the timing of the light exposure relative to the nadir of the endogenous rhythm, which usually is located at about 5:00 AM. Exposure to bright light before nadir induces a phase delay, whereas a phase advance is obtained with exposure to light after nadir. The paper describes how bright light treatment can be used to reduce the effects of jet lag and of night work, sleep phase disturbances and early morning awakenings. Melatonin administration is an alternative treatment for the same type of disorders, and is also discussed in the article.
Circadian Rhythm↗
Citalopram: differential sleep/wake and EEG power spectrum effects after single dose and chronic administration.
The sleep/wake effects of the selective serotonin re-uptake inhibitor citalopram were studied in both a single-dose study with three dose levels (0.5, 2.0 and 5.0 mg/kg), and a 5-week chronic administration study (15 mg/kg/24 h). Single doses of citalopram resulted in a dose-dependent inhibition of rapid eye movement (REM) sleep. After chronic citalopram treatment there was a sustained REM sleep inhibition. Single doses of citalopram resulted in only minor changes in non-REM (NREM) sleep as well as in NREM EEG power spectral density. Chronic administration resulted in a major shift from SWS-2 to SWS-1. The observed corresponding changes in EEG power density were regional. A 30 to 40 percent reduction of power density in the 0.5-15 Hz range in the fronto-parietal EEG derivation was seen for the whole 8-h registration period. In the fronto-frontal EEG derivation only minor changes were seen. A decreasing trend in NREM sleep power density between 0.5 and 7 Hz, usually seen during the course of the light period, was not observed in the chronic condition, but was seen in control and single-dose condition, suggesting altered diurnal distribution of slow wave activity in the chronic condition. The data indicate that acute and chronic administration of citalopram shows clear differences in sleep effect, which may be caused by alteration of serotonergic transmission, and may be related to the antidepressant effect.
Algorithms↗
Sleep and EEG power spectrum effects of the 5-HT1A antagonist NAN-190 alone and in combination with citalopram.
The sleep and waking and EEG power spectrum effects of the putative 5-HT1A antagonist NAN-190 (0.5 mg/kg, i.p.) were studied alone and in co-administration with the selective serotonin re-uptake inhibitor citalopram (5.0 mg/kg, i.p.) in the rat. Citalopram, as in a prior dose-response study, reduced REM sleep. In addition, a slight increase in NREM sleep was observed. Citalopram reduced NREM fronto-parietal (FP) EEG power density in the 5-20 Hz range. When administered alone, NAN-190 suppressed REM sleep in the first 2 h, and reduced SWS-2 in the first 4 after administration. NAN-190 also suppressed selectively NREM sleep slow-wave activity in both fronto-frontal (FF) and FP EEG power spectrum. When administered in combination with citalopram, an attenuation of the power density reduction in the 7-15 Hz range in the FF EEG of citalopram alone, was observed. However, the EEG power spectral density and REM sleep suppressive effects of NAN-190 were both augmented. The results are compatible with the notion that serotonin is involved in the modulation of the slow wave activity in the EEG during NREM sleep. The results are cordant with other data suggesting that postsynaptic 5-HT1A stimulation might increase slow wave activity in the NREM EEG, and that serotonergic stimulation of other receptor subtypes (possibly 5-HT2) may decrease slow wave activity in the NREM EEG.
Animals↗
Sleep effects following intrathecal administration of the 5-HT1A agonist 8-OH-DPAT and the NMDA antagonist AP-5 in rats.
The modulating effect of an intrathecally (i.t.) administered 5-HT1A agonist and an NMDA antagonist on sleep, waking and EEG power spectra was investigated in rats. The 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (38 nmol) increased total slow wave sleep (TSWS) and decreased waking over the 8 h recording period. The TSWS increase was mostly due to an increase in SWS1. Sleep latency to SWS1 was also reduced. The NMDA antagonist dl-2-amino 5-phosphonovaleric acid (AP-5) (31.5 nmol) reduced waking. SWS1 was increased, but TSWS was not changed. An increase in REM sleep was seen during the last part of the recording. Combined treatment with 8-OH-DPAT and AP-5 reduced waking and increased TSWS. No change in REM sleep was seen. There were no systematic changes in either waking, TSWS or REM fronto-frontal or fronto-parietal EEG power spectrum after any of the treatments. The results suggest that in the spinal cord stimulation of 5-HT1A receptors have a dampening effect on transmission of sensory information, leading to deactivation and thereby increased possibilities for sleep induction. Blockade of the NMDA receptors may also lead to a small dampening of sensory transmission with similar consequences.
2-Amino-5-phosphonovalerate↗
Lesion of descending 5-HT pathways increases zimeldine-induced waking in rats.
Sleep, waking, and EEG power spectra were investigated in rats with spinal 5,6-dihydroxytryptamine (5,6-DHT) lesions, following 20 mg/kg zimeldine or vehicle IP injections. 5,6-DHT selectively lesioned the descending serotonergic pathways. Lesion alone did not change sleep and waking stages compared to baseline, except for a reduction in REM sleep. Consistent with earlier findings, zimeldine in nonlesioned rats increased waking the first 2 h of recording. Zimeldine treatment in lesioned rats gave a significant additional 50% increase in waking the first 2 h and a corresponding decrease in total slow wave sleep, suggesting a potentiation of these effects. Zimeldine gave no significant changes in waking EEG power spectral density. Lesion gave a tendency to reduction between 4.0 and 15.5 Hz compared with baseline, and between 10.0 and 16.5 compared to the independent control group. In both comparisons, the combined treatment strengthened this effect, again suggesting a potentiating effect of lesion. In sleep, zimeldine reduced power over the whole spectrum (0.5-20.0 Hz), less in the lower frequencies than in the higher frequencies.
Afferent Pathways↗
Sleep/waking and EEG power spectrum effects of a nonselective serotonin (5-HT) antagonist and a selective 5-HT reuptake inhibitor given alone and in combination.
Sleep/waking stages, electroencephalogram (EEG) power spectra and behavior were studied in rats for 8 hours following intraperitoneal administration of a nonselective serotonin (5-HT) antagonist (0.1 and 2.0 mg/kg methiothepin) and a selective 5-HT reuptake inhibitor (20 mg/kg zimeldine), given alone and in combination. Consistent with earlier studies, zimeldine gave a biphasic effect on sleep and waking. Waking was increased and slow wave sleep (SWS)-2 decreased initially, followed by an increase in SWS-2 in the second 2-hour period. Rapid eye movement (REM) sleep was reduced throughout the experiment. EEG power densities were generally reduced in the higher frequencies, but the effect differed somewhat in the different vigilance states and between the fronto-frontal and fronto-parietal EEG leads. Zimeldine did not change behavior. Methiothepin, at 0.1 mg/kg, gave only minor effects by itself, but it blocked the initial waking increase of zimeldine. So did 2.0 mg/kg methiothepin, but this dose markedly changed sleep/waking stages by itself: SWS-1 was profoundly increased, whereas waking, SWS-2 and REM sleep were reduced. Total SWS (TSWS) was markedly increased due to the SWS-1 increase. Because TSWS was increased while SWS-2 was decreased following 2.0 mg/kg methiothepin, it is concluded that spindle activity was facilitated, whereas slow wave activity was antagonized. Methiothepin, at 2.0 mg/kg, also markedly changed EEG power densities within TSWS and induced cataleptic behavior. It is concluded that the initial waking increase of zimeldine depends on simultaneous activation of several different 5-HT receptor subtypes. The other zimeldine effects were not consistently antagonized, thus the mechanisms behind these effects remain unclear.
Animals↗
Strain differentiation of Neisseria meningitidis by small-fragment restriction endonuclease analysis (SF-REA).
Following an outbreak involving 3 cases of serogroup B meningococcal disease in a rural part of Western Norway, 2 clinical and 99 carrier isolates of Neisseria meningitidis were examined by small-fragment restriction endonuclease analysis (SF-REA) using EcoRI, to determine its potential for strain differentiation. SF-REA characterized all isolates and provided reproducible results with acceptable inter-clonal differentiation. The results of SF-REA correlated well with those of serological typing and were used to determine clonal diversity and prevalence of invasive strains among the carrier isolates. SF-REA was also useful in demonstrating acquisition of a new carrier strain after eradication of the initial strain by ofloxacin. Thirty-one different restriction patterns/pattern complexes were recognized among the 101 isolates. The two clinical isolates had identical restriction patterns and showed > or = 90% similarity to those of six carrier isolates. In three out of six apparent treatment failures, successful eradication of the original strain by ofloxacin was demonstrated by SF-REA. SF-REA proved valuable in strain differentiation of Neisseria meningitidis, complemented serology, and characterized all isolates which could not be typified by serology.
Carrier State↗
Small-fragment restriction endonuclease analysis in epidemiological mapping of group A streptococci.
The usefulness of small-fragment restriction endonuclease digest analysis (SF-REA) of group A streptococcal DNA with EcoRI, as a supplement to the more conventional T serotyping, was assessed for epidemiological characterisation. One hundred and thirty-five clinical isolates from 1988-1990 were examined. SF-REA provided characteristic fingerprints of all isolates, whereas eight isolates were non-typable by T serotyping. Generally, there was a striking correlation between the results obtained with the two techniques. Furthermore, SF-REA reliably classified the eight T-non-typable isolates and occasionally revealed subgroups within the T serotypes. In addition, SF-REA was useful for the clarification of discrepancies between serotyping results from two different reference laboratories. No obvious correlation was observed between the DNA fingerprints and the clinical manifestations of infection or the geographical origin of the group A streptococcal isolates. SF-REA is a valuable supplement to T typing in epidemiological studies and frequently appears to be a more efficient tool for strain differentiation.
Bacteremia↗