Cardiovascular effects of partial sleep deprivation in healthy volunteers

Dettoni JL, Consolim-Colombo FM, Drager LF, Rubira MC, de Souza SB, Irigoyen MC, Mostarda C, Borile S, Krieger EM, Moreno H Jr, Lorenzi-Filho G. Cardiovascular effects of partial sleep deprivation in healthy volunteers. J Appl Physiol 113: 232-236, 2012. First published April 26, 2012; doi: 10.1152/japplphysiol.01604.2011.-Sleep deprivation is common in Western societies and is associated with increased cardiovascular morbidity and mortality in epidemiological studies. However, the effects of partial sleep deprivation on the cardiovascular system are poorly understood. In the present study, we evaluated 13 healthy male volunteers (age: 31 +/- 2 yr) monitoring sleep diary and wrist actigraphy during their daily routine for 12 nights. The subjects were randomized and crossover to 5 nights of control sleep (>7 h) or 5 nights of partial sleep deprivation (<5 h), interposed by 2 nights of unrestricted sleep. At the end of control and partial sleep deprivation periods, heart rate variability (HRV), blood pressure variability (BPV), serum norepinephrine, and venous endothelial function (dorsal hand vein technique) were measured at rest in a supine position. The subjects slept 8.0 +/- 0.5 and 4.5 +/- 0.3 h during control and partial sleep deprivation periods, respectively (P < 0.01). Compared with control, sleep deprivation caused significant increase in sympathetic activity as evidenced by increase in percent low-frequency (50 +/- 15 vs. 59 +/- 8) and a decrease in percent high-frequency (50 +/- 10 vs. 41 +/- 8) components of HRV, increase in low-frequency band of BPV, and increase in serum norepinephrine (119 +/- 46 vs. 162 +/- 58 ng/ml), as well as a reduction in maximum endothelial dependent venodilatation (100 +/- 22 vs. 41 +/- 20%; P < 0.05 for all comparisons). In conclusion, 5 nights of partial sleep deprivation is sufficient to cause significant increase in sympathetic activity and venous endothelial dysfunction. These results may help to explain the association between short sleep and increased cardiovascular risk in epidemiological studies.

Selective REM sleep deprivation in narcolepsy

Narcolepsy is characterized by excessive daytime sleepiness and rapid eye movement (REM) sleep abnormalities, including cataplexy. The aim of this study was to assess REM sleep pressure and homeostasis in narcolepsy. Six patients with narcolepsy and six healthy controls underwent a REM sleep deprivation protocol, including one habituation, one baseline, two deprivation nights (D1, D2) and one recovery night. Multiple sleep latency tests (MSLTs) were performed during the day after baseline and after D2. During D1 and D2 REM sleep was prevented by awakening the subjects at the first polysomnographic signs of REM sleep for 2 min. Mean sleep latency and number of sleep-onset REM periods (SOREMs) were determined on all MSLT. More interventions were required to prevent REM sleep in narcoleptics compared with control subjects during D1 (57 ± 16 versus 24 ± 10) and D2 (87 ± 22 versus 35 ± 8, P = 0.004). Interventions increased from D1 to D2 by 46% in controls and by 53% in narcoleptics (P < 0.03). Selective REM sleep deprivation was successful in both controls (mean reduction of REM to 6% of baseline) and narcoleptics (11%). Both groups had a reduction of total sleep time during the deprivation nights (P = 0.03). Neither group had REM sleep rebound in the recovery night. Narcoleptics had, however, an increase in the number of SOREMs on MSLT (P = 0.005). There was no increase in the number of cataplexies after selective REM sleep deprivation. We conclude that: (i) REM sleep pressure is higher in narcoleptics; (ii) REM sleep homeostasis is similar in narcoleptics and controls; (iii) in narcoleptics selective REM sleep deprivation may have an effect on sleep propensity but not on cataplexy.

EEG correlation and power during maintenance of wakefulness test after sleep-deprivation

To investigate whether there are any objective EEG characteristics that change significantly between specific time periods during maintenance of wakefulness test (MWT) and whether such changes are associated with the ability to appropriately communicate sleepiness.

Contemporary role of androgen deprivation therapy for prostate cancer

Androgen deprivation therapy (ADT) for prostate cancer (PCa) represents one of the most effective systemic palliative treatments known for solid tumors. Although clinical trials have assessed the role of ADT in patients with metastatic and advanced locoregional disease, the risk-benefit ratio, especially in earlier stages, remains poorly defined. Given the mounting evidence for potentially life-threatening adverse effects with short- and long-term ADT, it is important to redefine the role of ADT for this disease.

Cyclic alternating pattern in narcolepsy patients and healthy controls after partial and total sleep deprivation

To investigate the regulation NREM sleep at baseline and in morning recovery sleep after partial and total sleep deprivation (SD) in narcolepsy-cataplexy (NC) using cyclic alternating pattern (CAP).

Outcome predictors of radical prostatectomy followed by adjuvant androgen deprivation in patients with clinical high risk prostate cancer and pT3 surgical margin positive disease

Patients with high risk prostate cancer with pT3 tumor and positive surgical margins have a high risk of biochemical failure after radical prostatectomy and adjuvant androgen deprivation therapy. Predictors of cancer related death in this patient group are necessary.

Sleep deprivation before stroke is neuroprotective: A pre-ischemic conditioning related to sleep rebound

BACKGROUND AND AIM: We have previously shown in a rat model of focal cerebral ischemia that sleep deprivation after stroke onset aggravates brain damage. Others reported that sleep deprivation prior to stroke is neuroprotective. The main aim of this study was to test the hypothesis that the neuroprotection may be related to an increase in sleep (sleep rebound) during the acute phase of stroke. METHODS: Male Sprague Dawley rats (n=36) were subjected to continuous polygraphic recordings for baseline, total sleep deprivation (TSD), and 24h after ischemia. TSD for 6h was performed by gentle handling and immediately followed by ischemia. Focal cerebral ischemia was induced by permanent occlusion of distal branches of the middle cerebral artery. Control experiments included ischemia without SD (nSD) and sham surgery with TSD (n=6/group). RESULTS: Shortly after stroke, the amount of slow wave sleep (SWS) and paradoxical sleep (PS) increased significantly (p<0.05) in the TSD/ischemia, resulting in an increase in the total sleep time by 30% compared to baseline, or by 20% compared with the nSD/ischemia group. The infarct volume decreased significantly by 50% in the TSD/ischemia compared to nSD group (p<0.02). Removal of sleep rebound by allowing TSD-rats sleep for 24h before ischemia eliminated the reduction in the infarct size. CONCLUSION PRESTROKE: Sleep deprivation results in sleep rebound and reduces brain damage. Sleep rebound may be causally related to the neuroprotection.

The Representation of Motherhood in Polish Cinema

The project aimed to analyse representations of motherhood in Polish cinema as a special case of a more general system within the representation of women. It concentrated on the image of the Polish Mother created during the 19th century in Polish culture under the influence of specific political, social and religious factors. Ms. Ostrowska's initial hypothesis was that this symbolic image became one of the most stable elements in Polish cinema and as her research revealed, it was valuable for the preservation of national identity but nevertheless a fiercely constraining model for Polish femininity. In order to fully understand the nature of this persistent image it was initially necessary to related it to broader contexts and issues in representation. These included the image of the Polish Mother within general mythological structures (using the notion of myth in the Barthesian sense). Following her initial research Ms. Ostrowska felt that it was most appropriate to view the myth of the Polish Mother as a dominant ideological structure in the discourse of motherhood within Polish culture. An analysis of the myth of the Polish Mother can provide an insight into how Polish society sees itself at different periods in time and how a national identity was constructed in relation to particular ideological demands stemming from concrete historical and political situations. The analysis of the film version of this myth also revealed some aspects of the national character of Polish cinema. There the image of woman has become enshrined as the "eternal feminine", with virtues which are inevitably derived directly from Catholicism, particularly in relation to the networks of meanings around the central figure of Mary, Mother of God. In 19th century Poland these were linked with patriotic values and images of woman became part of the defence of the very idea of Poland and Polishness. After World War Two, this religious-political image system was adapted to the demands of the new communist ideology. The possibility of manipulating the ideological dimensions of the myth of the Polish Mother is due to the very nature of the image, which as a symbol of civil religion had been able to function independently of any particular state or church institution. Although in communist ideology the stress was on the patriotic aspect of the myth, its pronounced religious aspect was also transmitted, consciously or not, in the denotation process, this being of great significance in the viewer's response to the female character. This appropriation of elements derived from the national patriotic tradition into the discourse of communist ideology was a very efficient strategy to establish the illusion of continuity in national existence, which was supposed to convince society of the rightness of the new political situation. The analysis of films made in the post-war period showed the persistence of this discourse on motherhood in a range of cinematic texts regardless of the changing political situation. Ms. Ostrowska claims that the stability of this discursive formation is to a certain extent the result of the mythological aspect of the mother figure. This mythological structure also belongs to the ideology of Romanticism which in general continues to prevail in Polish cultural discourse as a meta-language of national community. The analysis of the films confirmed the hypothesis of the Polish Mother as a myth-sign whose signifier is stable whereas the signified depends on the specific historical conditions in which it is set. Therefore in the famous propaganda documentary Kobiety naszych dni (Women of Our Days, 1951) by Jan Zelnik, and in other films made after the October 1956 "thaw" it functions as an "empty sign. She concludes that it would be difficult to deny that the myth of the Polish Mother has offered Polish women a special role in national life, granting them a high moral position in the social, hierarchy. However the processes of idealisation involved have resulted in a deprivation of her subjectivity and the right to decide about her own life. This idealisation also served to strengthen traditional patriarchal structures through this set of female obligations to the mother land. In Polish ideology it is not a man who demands sacrifice from a woman but the motherland, which, deprived of the institutions of male power for nearly 150 years, had functioned as a feminine structure. That is why oppressive aspects of the myth have been obscured for so long. While Polish women were doubtless able to accept the constrictions because of their sense of national duty and any misgivings were overridden by the argument of the cause, it is important to recognise that the strength of these constructions, compounded by the ways in which they spoke of and continue to speak of a certain perfection, make them persist into contemporary Poland. Poland is however no longer embattled and the signs that made these meanings are potentially empty. This space for meaning will be and is already being contested and increasingly colonised by current western models of femininity. Ms. Ostrowska's final question is whether this will help to prevent a possible resentful victimisation of the silent and noble Polish Mother.

Immediate or deferred androgen deprivation for patients with prostate cancer not suitable for local treatment with curative intent: European Organisation for Research and Treatment of Cancer (EORTC) Trial 30891

PURPOSE: This study (EORTC 30891) attempted to demonstrate equivalent overall survival in patients with localized prostate cancer not suitable for local curative treatment treated with immediate or deferred androgen ablation. PATIENTS AND METHODS: We randomly assigned 985 patients with newly diagnosed prostate cancer T0-4 N0-2 M0 to receive androgen deprivation either immediately (n = 493) or on symptomatic disease progression or occurrence of serious complications (n = 492). RESULTS: Baseline characteristics were well balanced in the two groups. Median age was 73 years (range, 52 to 81). At a median follow-up of 7.8 years, 541 of 985 patients had died, mostly of prostate cancer (n = 193) or cardiovascular disease (n = 185). The overall survival hazard ratio was 1.25 (95% CI, 1.05 to 1.48; noninferiority P > .1) favoring immediate treatment, seemingly due to fewer deaths of nonprostatic cancer causes (P = .06). The time from randomization to progression of hormone refractory disease did not differ significantly, nor did prostate-cancer specific survival. The median time to the start of deferred treatment after study entry was 7 years. In this group 126 patients (25.6%) died without ever needing treatment (44% of the deaths in this arm). CONCLUSION: Immediate androgen deprivation resulted in a modest but statistically significant increase in overall survival but no significant difference in prostate cancer mortality or symptom-free survival. This must be weighed on an individual basis against the adverse effects of life-long androgen deprivation, which may be avoided in a substantial number of patients with a deferred treatment policy.

Differential vulnerability of immature murine neurons to oxygen-glucose deprivation

In vivo studies support selective neuronal vulnerability to hypoxia-ischemia (HI) in the developing brain. Since differences in intrinsic properties of neurons might be responsible, pure cultures containing immature neurons (6-8 days in vitro) isolated from mouse cortex and hippocampus, regions chosen for their marked vulnerability to oxidative stress, were studied under in vitro ischemic conditions-oxygen-glucose deprivation (OGD). Twenty-four hours of reoxygenation after 2.5 h of OGD induced significantly greater cell death in hippocampal than in cortical neurons (67.8% vs. 33.4%, P = 0.0068). The expression of neuronal nitric oxide synthase (nNOS) protein, production of nitric oxide (NO), and reactive oxygen species (ROS), as well as glutathione peroxidase (GPx) activity and intracellular levels of reduced glutathione (GSH), were measured as indicators of oxidative stress. Hippocampal neurons had markedly higher nNOS expression than cortical neurons by 24 h of reoxygenation, which coincided with an increase in NO production, and significantly greater ROS accumulation. GPx activity declined significantly in hippocampal but not in cortical neurons at 4 and 24 h after OGD. The decrease in GSH level in hippocampal neurons correlated with the decline of GPx activity. Our data suggest that developing hippocampal neurons are more sensitive to OGD than cortical neurons. This finding supports our in vivo studies showing that mouse hippocampus is more vulnerable than cortex after neonatal HI. An imbalance between excess prooxidant production (increased nNOS expression, and NO and ROS production) and insufficient antioxidant defenses created by reduced GPx activity and GSH levels may, in part, explain the higher susceptibility to OGD of immature hippocampal neurons.