Francieli Silva Ruiz

Immune alterations after selective rapid eye movement or total sleep deprivation in healthy male volunteers.

We investigated the impact of two nights of total sleep deprivation (SD) or four nights of rapid eye movement (REM) SD on immunological parameters in healthy men. Thirty-two volunteers were randomly assigned to three protocols (control, total SD or REM SD). Both SD protocols were followed by three nights of sleep recovery. The control and REM SD groups had regular nights of sleep monitored by polysomnography. Circulating white blood cells (WBCs), T- (CD4/CD8) and B-lymphocytes, Ig classes, complement and cytokine levels were assessed daily. Two nights of total SD increased the numbers of leukocytes and neutrophils compared with baseline levels, and these levels returned to baseline after 24 h of sleep recovery. The CD4+ T-cells increased during the total SD period (one and two nights) and IgA levels decreased during the entire period of REM SD. These levels did not return to baseline after three nights of sleep recovery. Levels of monocytes, eosinophils, basophils and cytokines (IL-1β, IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ) remained unchanged by both protocols of SD. Our findings suggest that both protocols affected the human immune profile, although in different parameters, and that CD4+ T-cells and IgA levels were not re-established after sleep recovery.

Sleep deprivation reduces the lymphocyte count in a non-obese mouse model of type 1 diabetes mellitus

The objective of the present study was to determine whether sleep deprivation (SD) would promote changes in lymphocyte numbers in a type 1 diabetes model (non-obese diabetic, NOD, mouse strain) and to determine whether SD would affect female and male NOD compared to Swiss mice. The number of lymphocytes in peripheral blood after 24 and 96 h of SD (by multiple platform method) or equivalent period of time in home-cage controls was examined prior to the onset of diabetes. SD for 96 h significantly reduced lymphocytes in male Swiss mice compared to control (8.6 +/- 2.1 vs 4.1 +/- 0.7 10(3)/microL; P < 0.02). In male NOD animals, 24- and 96-h SD caused a significant decrease of lymphocytes compared to control (4.4 +/- 0.3 vs 1.6 +/- 0.5; P < 0.001 and 4.4 +/- 0.3 vs 0.9 +/- 0.1 10(3)/microL; P < 0.00001, respectively). Both 24- and 96-h SD induced a reduction in the number of lymphocytes in female Swiss (7.5 +/- 0.5 vs 4.5 +/- 0.5, 4.4 +/- 0.6 10(3)/microL; P < 0.001, respectively) and NOD mice (4 +/- 0.6 vs 1.8 +/- 0.2, 1.2 +/- 0.4 10(3)/microL; P < 0.01, respectively) compared to the respective controls. Loss of sleep induced lymphopenia in peripheral blood in both genders and strains used. Since many cases of autoimmunity present reduced numbers of lymphocytes and, in this study, it was more evident in the NOD strain, our results suggest that SD should be considered a risk factor in the onset of autoimmune disorders.

Impairment of the mitochondrial electron transport chain due to sleep deprivation in mice

It has been demonstrated that sleep deprivation is associated with altered expression of genes related to metabolic processes, response to stress and inflammation, circadian sleep/wake cycles, regulation of cell proliferation and various signaling pathways. However, the molecular mechanisms underlying these changes remain poorly understood. Thus, the present study aims to characterize the function of the mitochondrial electron transport chain in the brain using an animal model of paradoxical sleep deprivation (PSD). The question of whether sleep recovery (rebound) can reverse changes found after PSD is also addressed. Adult male inbred C57BL/6J mice were randomly distributed into three groups: home-cage control, PSD and sleep rebound groups. The PSD and rebound groups were subjected to PSD for 72 h. After this sleep deprivation period, the rebound group was returned to its home cage and allowed to sleep in an undisturbed and spontaneous fashion for 24h. The mitochondrial complex I-III, complex II, succinate dehydrogenase and complex II-III activities were then measured by spectrophotometric methods in sub-mitochondrial particles extracted from the prefrontal cortex, hippocampus, striatum and hypothalamus. Our results showed a significant decrease in the activity of complex I-III in the PSD and rebound groups as compared to the control group. The complex II and II-III activity were particularly decreased in the hypothalamus of the sleep rebound group. These results are consistent with the involvement of sleep in energy metabolism and corroborate previous experiments demonstrating the importance of the hypothalamus in sleep regulation.

Immune Outcomes of Paradoxical Sleep Deprivation on Cellular Distribution in Naive and Lipopolysaccharide-Stimulated Mice

Background/Aims: Several lines of evidence indicate that sleep loss imposes significant consequences on the host defense system, including changes in cell number, activity and distribution. However, it is not clear whether cellular alterations after sleep deprivation are caused by redistribution to immune organs or by death of these cells or how the response to a nonspecific immune activator would be affected. Therefore, the aim of this study was to assess the leukocyte distribution after paradoxical sleep deprivation (PSD) in saline- and lipopolysaccharide-treated mice. Methods: Adult inbred mice were paradoxical sleep deprived (72 h), whereas the controls were kept in their home cages. After PSD, both groups received an injection of either saline or lipopolysaccharide (LPS; 1 or 5 µg/animal, intraperitoneally), 2 h prior to the collection of blood, spleen, lymph nodes and peritoneal wash. Isolated cells were then designated to differential leukocyte count (blood) and flow cytometry analysis of immune cell subsets (immune sites). Results: The data revealed that PSD caused a significant reduction of circulating lymphocytes and a general decrease in all cellular subsets of spleen, mainly T and B cells. However, no alteration in response of PSD was found on other immune sites, such as lymph nodes and peritoneum. Of note, immune cell distribution in response to in vivo LPS stimulation remained unchanged after PSD. Conclusions: Our study provided original evidence concerning the immune outcomes of PSD, indicating that cellular decrease caused by PSD is not restricted to circulation, but also to immune sites. Taken together, our results could help shed light on the physiological mechanisms of leukocyte trafficking.

Sleep Deprivation Increases Mortality in Female Mice Bearing Ehrlich Ascitic Tumor

Objectives: Sleep deprivation is a growing public health hazard, yet it is still under-recognized. Sleep disorders and disruption of sleep patterns may compromise the immune function and adversely affect host resistance to infectious diseases. This is a particular risk in cancer patients, who report a high frequency of sleep disturbances. The present study investigated the effects of sleep deprivation on the development of Ehrlich ascitic tumors (EAT) in female BALB/c mice. Our study also evaluated whether EAT would induce alterations in sleep pattern. Spleen lymphocyte cell populations and mortality were also quantified. Methods: Female BALB/c mice were intraperitoneally inoculated with EAT cells. Immediately after the inoculation procedure, animals were sleep deprived for 72 h. Ten or 15 days after inoculation, the number of tumoral cells was quantified and the lymphocytic cell population in the spleen was characterized by flow cytometry. In addition, the effect of sleep deprivation on EAT-induced mortality was quantified and the influence of EAT on sleep patterns was determined. Results: Sleep deprivation did not potentiate EAT growth, but it significantly increased mortality. Additionally, both EAT and sleep deprivation decreased frequencies of splenic CD4+, CD8+ and CD19+ cells. With respect to sleep patterns, EAT significantly enhanced paradoxical sleep time. Conclusions: Although sleep deprivation did not potentiate EAT growth, it decreased the survival of female tumor-bearing mice.

Can morphine interfere in the healing process during chronic stress

Technological advances, constant pressure, increased qualified demand, and other daily activities present in modern society result in increasingly stressful living conditions for the population. In the short term, the release of stress-related hormones can play a key role in the survival of an organism. However, it is well known that chronic exposure to cortisol can lead to many adverse effects. Several findings show immunological changes in response to chronic exposure to cortisol, in particular in skin integrity, which may interfere with the healing process. Morphine is an immunosuppressive drug, and when it is used chronically, it can lead to an increased incidence of infections and a delay in the healing process. The importance of opiates as analgesics in the medical setting is indisputable. However, there are a limited number of studies in this field. These investigations can provide further understanding of the mechanisms involved in the healing process in morphine-dependent individuals under chronic stress, which is a common condition in modern society. Furthermore, medical prescriptions of opiates are common among terminal patients, who frequently develop decubitus ulcers and bacterial infections. This review is aimed to provide a concise analysis of effects of morphine and stress on the healing process.

Sleep influences the immune response and the rejection process alters sleep pattern: Evidence from a skin allograft model in mice

INTRODUCTION Sleep generally regulates immune functions in a supportive manner and can affect parameters that are directly involved in the rejection process. STUDY OBJECTIVES The first objective was to assess whether sleep deprivation (SD) or sleep restriction (SR) affects the allograft rejection process in mice. The second objective was to investigate whether the rejection process itself modulates the sleep pattern of allografted mice. DESIGN Adult BALB/c and C57BL/6J male mice were used as the donors and recipients, respectively, except for the syngeneic group (ISOTX), which received skin from mice of the same strain (C57BL/6J). The recipients were randomly assigned to either one of two control groups - TX (allogenic) or ISOTX (syngeneic) - which underwent stereotaxic surgery to enable sleep recording prior to the allograft but were not sleep deprived; one of two paradoxical sleep deprived groups - SDTX and TXSD - which underwent 72h of continuous SD either before or after the allograft respectively, and one of two sleep restricted groups - SRTX and TXSR - which underwent 21h of SD and 3h of sleep for 15days either before or after the allograft respectively. INTERVENTIONS The skin allograft was inspected daily to determine the survival time, expected as 8.0±0.4days in this transplant model under no treatment. The sleep pattern was controlled throughout the rejection process in the SD and SR groups. Draining lymph nodes, spleen, blood and skin grafts were harvested on the 5th day after transplantation for evaluation of the immune parameters related to allograft rejection. MEASUREMENTS AND RESULTS In the control groups, we observed a reduction in paradoxical sleep throughout the entire allograft rejection process. Acute and chronic experimental sleep loss in the SD and SR groups produced marked alterations in the immune response. Both SD and SR prolonged allograft survival compared to the non-sleep-deprived group. There were reductions in the following parameters involved in the allograft rejection under sleep loss: CD4+ and CD8+ T cell subpopulations in the peripheral lymph organs and spleen, circulating sIL-2R levels, graft-infiltrating CD4+ T cells and skin allograft global gene expression. CONCLUSIONS We provide, as far as we are aware, the first evidence in vivo that the immune response can alter the normal sleep pattern, and that sleep loss can conversely affect the immune response related to graft rejection.

Sleep quality and psychobiological aspects of Brazilian Paralympic athletes in the London 2012 pre-Paralympics period

O objetivo do estudo foi avaliar os aspectos psicobiologicos de atletas da modalidade de atletismo Paralimpico, antes dos Jogos Paralimpicos de Londres de 2012. Foram avaliados 40 atletas, sem 31 homens e 9 mulheres que foram convocados pelo Comite Paralimpico Brasileiro para fazer parte da Delegacao Brasileira. Para a avaliacao dos aspectos psicobiologicos nos utilizamos os questionarios: Inventario de Ansiedade Traco-Estado, POMS, Inventario de Depressao de Beck, questionario de Pittsburgh Escala de Epworth para avaliar, respectivamente, a ansiedade, o humor, a depressao, o sono e a sonolencia. Para ansiedade-traco e ansiedade-estado os atletas apresentaram nivel medio de ansiedade, em relacao ao perfil dos estados de humor, a dimensao vigor apresentou valores mais altos do que as outras dimensoes. O tempo total de sono foi menor em atletas com o sono ruim, a eficiencia de sono foi menor em atletas com sono ruim e o tempo total de sono foi menor para quem teve eficiencia < 85%. Todas as variaveis psicobiologicas avaliadas no periodo pre-competitivo estavam dentro da normalidade para os atletas da equipe Paralimpica Brasileira de atletismo que participaram dos Jogos Paralimpicos de Londres 2012.O objetivo do estudo foi avaliar os aspectos psicobiologicos de atletas da modalidade de atletismo Paralimpico, antes dos Jogos Paralimpicos de Londres de 2012. Foram avaliados 40 atletas, sem 31 homens e 9 mulheres que foram convocados pelo Comite Paralimpico Brasileiro para fazer parte da Delegacao Brasileira. Para a avaliacao dos aspectos psicobiologicos nos utilizamos os questionarios: Inventario de Ansiedade Traco-Estado, POMS, Inventario de Depressao de Beck, questionario de Pittsburgh Escala de Epworth para avaliar, respectivamente, a ansiedade, o humor, a depressao, o sono e a sonolencia. Para ansiedade-traco e ansiedade-estado os atletas apresentaram nivel medio de ansiedade, em relacao ao perfil dos estados de humor, a dimensao vigor apresentou valores mais altos do que as outras dimensoes. O tempo total de sono foi menor em atletas com o sono ruim, a eficiencia de sono foi menor em atletas com sono ruim e o tempo total de sono foi menor para quem teve eficiencia < 85%. Todas as variaveis psicobiologicas avaliadas no periodo pre-competitivo estavam dentro da normalidade para os atletas da equipe Paralimpica Brasileira de atletismo que participaram dos Jogos Paralimpicos de Londres 2012.

Sleep deprivation predisposes allergic mice to neutrophilic lung inflammation

Background: Although different studies associated sleep deprivation (SD) with systemic inflammatory changes, the effect of sleep duration on the pathology of allergic chronic diseases is poorly understood. Objective: We sought to evaluate the influence of SD on allergen‐induced pulmonary inflammation. Methods: Ovalbumin (OVA)–sensitized C57BL/6 mice were exposed to a first set of intranasal OVA challenge under SD or healthy sleep (HS) conditions, followed by a second OVA challenge, 1 week apart. Some groups were subjected to corticosteroid treatment with dexamethasone. Results: OVA‐sensitized mice with SD had more severe airway inflammation than the allergic group with HS. Analysis of lung parenchyma revealed that the inflammation in allergic mice with SD was marked by an influx of neutrophils (mainly) and eosinophils and secretion of IL‐6, TNF‐&agr;, and IL‐17 in contrast to the eosinophilic inflammation and IL‐4 production observed in allergic mice with HS. The same cytokine profile was observed in ex vivo culture of cervical lymph node cells and splenocytes, indicating that in allergic mice SD favors immune responses toward a proinflammatory TH17 profile. This idea is supported by the fact that disruption of IL‐17 signaling (IL‐17 receptor A−/−) prevented airway neutrophilia in allergic mice with SD. Furthermore, allergic mice with SD became refractory to corticosteroid treatment in contrast to the allergic group with HS. Conclusion: Collectively, our data show that sleep quality participates in the progression of allergen‐induced eosinophilic lung inflammation to corticosteroid‐refractory neutrophilic manifestation.

Physiological and lipid profile response to acute exercise at different intensities in individuals with spinal cord injury

Study design:Experimental and cross-sectional study.Objective:To assess the immediate effect of exercise on heart rate (HR), oxygen uptake (VO2), pulmonary ventilation (PV), oxygen pulse (OP), glucose and lipids of wheelchair basketball players with spinal cord injury (SCI).Setting:Center of Studies in Psychobiology and Exercise—São Paulo, Brazil.Methods:In all, nine wheelchair basketball players with SCI and nine able-bodied controls (C) performed three exercise sessions at different intensities: ventilatory threshold 1 (VT1), 15% below VT1 and 15% above VT1 with a duration of ~24–34 min. HR, VO2, PV, OP, glucose and lipids were analyzed.Results:VO2, PV and OP were significantly lower in the players with SCI compared to C during the same intensity exercise sessions. However, the individuals with SCIs demonstrated increases in HR, PV and OP at similar rates to C. Triglycerides of the SCI group were elevated 30 min after the exercise session at VT1 compared to values before the exercise session (P=0.017); this elevation was not observed in group C. For the exercise sessions 15% above VT1, only glucose (P=0.040) and low-density lipoprotein (P=0.012) 30 min after the exercise were elevated in the SCI group compared to group C.Conclusion:We conclude that the SCI group demonstrated increases in HR, PV and OP but not VO2 with increased intensity of exercise at similar rates as in group C.