The Impact of Sleep Restriction and Simulated Physical Firefighting Work on Acute Inflammatory Stress Responses

Objectives

This study investigated the effect restricted sleep has on wildland firefighters’ acute cytokine levels during 3 days and 2 nights of simulated physical wildfire suppression work.

Methods

Firefighters completed multiple days of physical firefighting work separated by either an 8-h (Control condition; n = 18) or 4-h (Sleep restriction condition; n = 17) sleep opportunity each night. Blood samples were collected 4 times a day (i.e., 06:15, 11:30, 18:15, 21:30) from which plasma cytokine levels (IL-6, IL-8, IL-1β, TNF-α, IL-4, IL-10) were measured.

Results

The primary findings for cytokine levels revealed a fixed effect for condition that showed higher IL-8 levels among firefighters who received an 8-h sleep each night. An interaction effect demonstrated differing increases in IL-6 over successive days of work for the SR and CON conditions. Fixed effects for time indicated that IL-6 and IL-4 levels increased, while IL-1β, TNF-α and IL-8 levels decreased. There were no significant effects for IL-10 observed.

Conclusion

Findings demonstrate increased IL-8 levels among firefighters who received an 8-h sleep when compared to those who had a restricted 4-h sleep. Firefighters’ IL-6 levels increased in both conditions which may indicate that a 4-h sleep restriction duration and/or period (i.e., 2 nights) was not a significant enough stressor to affect this cytokine. Considering the immunomodulatory properties of IL-6 and IL-4 that inhibit pro-inflammatory cytokines, the rise in IL-6 and IL-4, independent of increases in IL-1β and TNF-α, could indicate a non-damaging response to the stress of simulated physical firefighting work. However, given the link between chronically elevated cytokine levels and several diseases, further research is needed to determine if firefighters’ IL-8 and IL-6 levels are elevated following repeated firefighting deployments across a fire season and over multiple fire seasons.     

Effect of one night of sleep loss on changes in tumor necrosis factor alpha (TNF-α) levels in healthy men

Total sleep deprivation in humans is associated with increased daytime sleepiness, decreased performance, elevations in inflammatory cytokines, and hormonal/metabolic disturbances.To assess the effects of 40 h of total sleep deprivation (TSD) under constant and well controlled conditions, on plasma levels of TNF-α and its receptor (TNFR1), interleukin-6 (IL-6), cortisol and C-reactive protein (CRP), sleepiness and performance, 12 healthy men (29 ± 3 years) participated in a 5-days sleep deprivation experiment (two control nights followed by a night of sleep loss and one recovery night). Between 0800 and 2300 (i.e. between 25 and 40 h of sleep deprivation), a serial of blood sampling, multiple sleep latency, subjective levels of sleepiness and reaction time tests were completed before (day 2: D2) and after (day 4: D4) one night of sleep loss. We showed that an acute sleep deprivation (i.e. after 34 and 37 h of sleep deprivation) induced a significant increase in TNF-α (P < 0.01), but there were no significant changes in TNFR1, IL-6, cortisol and CRP. In conclusion, our study in which constant and controlled experimental conditions were realized with healthy subjects and in absence of psychological or physical stressors, an acute total sleep deprivation (from 34 h) was sufficient to induce secretion of pro-inflammatory cytokine such as TNF-α, a marker more described in chronic sleep restriction or deprivation and as mediators of excessive sleepiness in humans in pathological conditions.     

Effects of Artificial Dawn and Morning Blue Light on Daytime Cognitive Performance,Well-being,Cortisol and Melatonin Levels

Light exposure elicits numerous effects on human physiology and behavior, such as better cognitive performance and mood. Here we investigated the role of morning light exposure as a countermeasure for impaired cognitive performance and mood under sleep restriction (SR). Seventeen participants took part of a 48h laboratory protocol, during which three different light settings (separated by 2?wks) were administered each morning after two 6-h sleep restriction nights: a blue monochromatic LED (light-emitting diode) light condition (BL; 100?lux at 470?nm for 20?min) starting 2?h after scheduled wake-up time, a dawn-simulating light (DsL) starting 30?min before and ending 20?min after scheduled wake-up time (polychromatic light gradually increasing from 0 to 250?lux), and a dim light (DL) condition for 2?h beginning upon scheduled wake time (<8?lux). Cognitive tasks were performed every 2?h during scheduled wakefulness, and questionnaires were administered hourly to assess subjective sleepiness, mood, and well-being. Salivary melatonin and cortisol were collected throughout scheduled wakefulness in regular intervals, and the effects on melatonin were measured after only one light pulse. Following the first SR, analysis of the time course of cognitive performance during scheduled wakefulness indicated a decrease following DL, whereas it remained stable following BL and significantly improved after DsL. Cognitive performance levels during the second day after SR were not significantly affected by the different light conditions. However, after both SR nights, mood and well-being were significantly enhanced after exposure to morning DsL compared with DL and BL. Melatonin onset occurred earlier after morning BL exposure, than after morning DsL and DL, whereas salivary cortisol levels were higher at wake-up time after DsL compared with BL and DL. Our data indicate that exposure to an artificial morning dawn simulation light improves subjective well-being, mood, and cognitive performance, as compared with DL and BL, with minimal impact on circadian phase. Thus, DsL may provide an effective strategy for enhancing cognitive performance, well-being, and mood under mild sleep restriction.     

Daytime napping after a night of sleep loss decreases sleepiness, improves performance, and causes beneficial changes in cortisol and interleukin-6 secretion

Sleep loss has been associated with increased sleepiness, decreased performance, elevations in inflammatory cytokines, and insulin resistance. Daytime napping has been promoted as a countermeasure to sleep loss. To assess the effects of a 2-h midafternoon nap following a night of sleep loss on postnap sleepiness, performance, cortisol, and IL-6, 41 young healthy individuals (20 men, 21 women) participated in a 7-day sleep deprivation experiment (4 consecutive nights followed by a night of sleep loss and 2 recovery nights). One-half of the subjects were randomly assigned to take a midafternoon nap (1400-1600) the day following the night of total sleep loss. Serial 24-h blood sampling, multiple sleep latency test (MSLT), subjective levels of sleepiness, and psychomotor vigilance task (PVT) were completed on the fourth (predeprivation) and sixth days (postdeprivation). During the nap, subjects had a significant drop in cortisol and IL-6 levels (P < 0.05). After the nap they experienced significantly less sleepiness (MSLT and subjective, P < 0.05) and a smaller improvement on the PVT (P < 0.1). At that time, they had a significant transient increase in their cortisol levels (P < 0.05). In contrast, the levels of IL-6 tended to remain decreased for approximately 8 h (P = 0.1). We conclude that a 2-h midafternoon nap improves alertness, and to a lesser degree performance, and reverses the effects of one night of sleep loss on cortisol and IL-6. The redistribution of cortisol secretion and the prolonged suppression of IL-6 secretion are beneficial, as they improve alertness and performance.     

Effect of immunological stress to neuroendocrine and gene expression in different swine breeds

Immunological stress is the status of animal in active immune when they are challenged by bacterial, virus and endocrine. It is associated with immunological, neurological, and endocrinological response. An immunological stress model was established in this study using Chinese indigenous breed (Laiwu), crossbred (Lulai), and exotic breed (Yorkshire), to explore the capacity of immunological stress resistance among different breeds. The study was also to reveal the effect of chromium yeast to immunological stress. 48 post-weaning piglets were taken from three breeds, 16 piglets of each breed from Laiwu, Lulai and Yorkshire. The experiment was designed as 2 × 2 factors, immunological stress (Saline, LPS) and Chromium (with Cr, without Cr). There were four treatments: control, LPS, Cr, and Cr+LPS. Blood parameters related to immunological stress, such as IL-1β, TNF-α, GH, and cortisol, were examined after blood sample were taken at 0, 2, 5, and 7 h of post-injection. The results showed that IL-1β, TNF-α, and cortisol increased in group of LPS treatment while GH declined at 2 h of post-injection in comparison to the control (p < 0.01). However, IL-1β, TNF-α, and cortisol in group of Cr+LPS were lower than that in group of LPS while GH were higher (p < 0.05). Total RNA was extractedfrom blood lymphocytes separation samples at 2 h of post-injection. Q-PCR was applied to determine the gene expression of IL-1β, IL-6 and TNF-α. The results showed that LPS injection increased the gene expression of IL-1β, IL-6 and TNF-α. Among three breeds, the expression of IL-1β, IL-6 and TNF-α in Yorkshire were significantly higher than in Laiwu and Lulai (p < 0.05), but there was no difference between Laiwu and Lulai. Among four treatments, the expression of three genes in group of LPS was the highest, compared to the group of Cr+LPS (p < 0.05) and control (p < 0.01). This study concluded that Laiwu had stronger capacity of immunological stress resistance and next was Lulai among three breeds. Chromium yeast helped piglets relieve immunological stress.     

Sleep Restriction during Simulated Wildfire Suppression: Effect on Physical Task Performance

Objectives

To examine the effects of sleep restriction on firefighters’ physical task performance during simulated wildfire suppression.

Methods

Thirty-five firefighters were matched and randomly allocated to either a control condition (8-hour sleep opportunity, n = 18) or a sleep restricted condition (4-hour sleep opportunity, n = 17). Performance on physical work tasks was evaluated across three days. In addition, heart rate, core temperature, and worker activity were measured continuously. Rate of perceived and exertion and effort sensation were evaluated during the physical work periods.

Results

There were no differences between the sleep-restricted and control groups in firefighters’ task performance, heart rate, core temperature, or perceptual responses during self-paced simulated firefighting work tasks. However, the sleep-restricted group were less active during periods of non-physical work compared to the control group.

Conclusions

Under self-paced work conditions, 4 h of sleep restriction did not adversely affect firefighters’ performance on physical work tasks. However, the sleep-restricted group were less physically active throughout the simulation. This may indicate that sleep-restricted participants adapted their behaviour to conserve effort during rest periods, to subsequently ensure they were able to maintain performance during the firefighter work tasks. This work contributes new knowledge to inform fire agencies of firefighters’ operational capabilities when their sleep is restricted during multi-day wildfire events. The work also highlights the need for further research to explore how sleep restriction affects physical performance during tasks of varying duration, intensity, and complexity.     

Interleukins 1α and 1β as regulators of steroidogenesis in human NCI-H295R adrenocortical cells

Inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) regulate the activity of the hypothalamo-pituitary-adrenal (HPA) axis at several levels. Although hypothalamic CRH secretion may be the primary mechanism by which these cytokines activate the HPA axis, IL-1 expression is increased within the adrenal glands in models for systemic inflammation, and IL-1 may augment adrenal glucocorticoid production. Our aim was to investigate the direct effects of IL-1α and IL-1β on adrenal steroidogenesis and expression of three key steroidogenic genes in human adrenocortical cells using the NCI-H295R cell line as a model. mRNAs encoding receptors for IL-1, TNF-α, and leukemia inhibitory factor (LIF) were detectable in the cell line (Affymetrix microarray analysis). Both IL-1α and IL-1β increased cortisol, androstenedione, dehydroepiandrosterone and dehydroepiandrosterone sulfate production, and the accumulation of mRNAs for steroidogenic acute regulatory protein (STAR), 17α-hydroxylase/17,20-lyase (CYP17A1) and 3β-hydroxysteroid dehydrogenase 2 (HSD3B2) in these cells (P<0.05 for all). Both ILs augmented TNF-α- and LIF-induced STAR and CYP17A1 mRNA accumulation, and TNF-α-induced cortisol production (P<0.05 for all). Both ILs also increased the apoptotic index of the cells (P<0.05), which was efficiently neutralized by their specific antibodies. The IL-induced changes in the STAR, HSD3B2, and CYP17A1 protein levels were not as evident as those in the respective mRNA levels. In conclusion, the combined effect of inflammatory cytokines at the adrenal level in acute or chronic inflammatory states could significantly stimulate glucocorticoid production, and thus explain the observed discrepancy between the cortisol and ACTH concentrations sometimes seen in sepsis and chronic inflammatory states.     

Narrow-band ultraviolet B (NB UV-B) exposures improve mood in healthy individuals differently depending on chronotype

ABSTRACT

The evening chronotype is associated with psychological symptoms such as depressed mood, while skin exposure to ultraviolet radiation (UVR) may affect mood and behavior through neural and humoral routes. This pilot study aimed to investigate the impact of whole-body narrow-band (NB) UV-B exposure on current mood state and circulating 25-hydroxyvitamin D3 (25(OH)D₃), interleukin-6 (IL-6), cortisol and β-endorphin (β-END) levels in healthy participants. Here, eleven healthy women received full-body NB UV-B exposures on four afternoons, and the chronotype was assessed with a shortened version of Horne and Östberg’s Morningness-Eveningness Questionnaire (MEQ). Perceived mood was evaluated using the Visual Analogue Scale (VAS), and serum 25(OH)D₃, IL-6, cortisol and β-END concentrations were monitored daily. Decreasing VAS values showed mood to improve significantly over the five days after the four suberythematous NB UV-B exposures (p = .038), and the more the circadian preference was inclined toward eveningness, the greater the improvement in the mood dimension of wellbeing (p = .021). Baseline mood state was correlated with baseline 25(OH)D₃ (r = ?0.54, 95% CI: ?0.86 to ?0.09) and with baseline cortisol (r = ?0.57, 95% CI: ?0.87 to ?0.04). During the NB UV-B exposures, 25(OH)D₃ increased significantly, as expected, and IL-6 declined significantly by ?0.35 (95% CI: ?0.69 to ?0.07) pg/mL from the initial values of 1.12 ± 0.66 pg/mL (p = .025). In conclusion, in our pilot study, NB UV-B exposure improved mood, especially among those with evening preference for their daily activities, as well as circulating 25(OH)D₃ levels, whereas circulating IL-6 levels decreased.

Abbreviations: UVR: Ultraviolet radiation; NB UV-B: narrow-band UV-B; VAS: Visual Analogue Scales; β-END: β-endorphin; IL-6: Interleukin-6     

Effect of Danshen aqueous extract on serum hs-CRP, IL-8, IL-10, TNF-α levels, and IL-10 mRNA, TNF-α mRNA expression levels, cerebral TGF-β1 positive expression level and its neuroprotective mechanisms in CIR rats

To observe the effects of Danshen aqueous extract (DSAE) on the cerebral tissue and nerve stem cells in cerebral ischemia reperfusion (CIR) rats. The model rats were prepared by occlusion of the middle cerebral artery for 2 h and then by reperfusion. They were randomly divided into five groups: a control group, an CIR group and three DSAE-treated groups. As compared with the sham control group, there was significant increase (P < 0.05, P < 0.01) in the serum high-sensitivity C-reactive protein (hs-CRP) and interleukin-8 (IL-8) levels, interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α) levels, and IL-10 mRNA, TNF-α mRNA expression levels, function score, Infarct size, TUNEL + cell counts, cerebral transforming growth factor beta 1 (TGF-β1) positive expression and cerebral neuron specific enolase (NSE) levels, and decrease in fas-associated protein with death domain (FADD) and death-associated protein (Daxx) positive expression levels in the CIR group. Compared with CIR group, DSAE treatment dose-dependently significantly decreased serum hs-CRP, IL-8, IL-10, TNF-α levels, and IL-10 mRNA, TNF-α mRNA expression levels, function score, Infarct size, TUNEL + cell counts, cerebral TGF-β1 positive expression and cerebral NSE levels, and increase FADD and Daxx positive expression levels in the CIR + DSAE groups. Taken together, these results suggest that DSAE has a neuroprotective role in the CIR rats, which may be related to improvement of immunity function, proteins and genes expression.     

Late bedtimes prevent circadian phase advances to morning bright light in adolescents

ABSTRACT

We examined phase shifts to bright morning light when sleep was restricted by delaying bedtimes. Adolescents (n = 6) had 10-h sleep/dark opportunities for 6 days. For the next 2 days, half were put to bed 4.5 h later and then allowed to sleep for 5.5 h (evening room light + sleep restriction). The others continued the 10-h sleep opportunities (sleep satiation). Then, sleep schedules were gradually shifted earlier and participants received bright light (90 min, ~6000 lux) after waking for 3 days. As expected, sleep satiation participants advanced (~2 h). Evening room light + sleep restriction participants did not shift or delayed by 2–4 h.

Abbreviations: DLMO: dim light melatonin onset.     

Chronic Inflammation Alters Production and Release of Glutathione and Related Thiols in Human U373 Astroglial Cells

Neurons rely on glutathione (GSH) and its degradation product cysteinylglycine released by astrocytes to maintain their antioxidant defences. This is particularly important under conditions of inflammation and oxidative stress, as observed in many neurodegenerative diseases including Alzheimer’s disease (AD). The effects of inflammatory activation on intracellular GSH content and the extracellular thiol profile (including cysteinylglycine and homocysteine) of astrocytes were investigated. U373 astroglial cells exposed to IL-1β and TNF-α for up to 96 h showed a dose-dependent increase in IL-6 release, indicative of increasing pro-inflammatory cellular activation. With increasing concentrations of IL-1β and TNF-α (0.01–1 ng/ml), an increase in both intracellular and extracellular GSH levels was observed, followed by a return to control levels in response to higher concentrations of IL-1β and TNF-α. Extracellular levels of cysteinylglycine decreased in response to all concentrations of IL-1β and TNF-α. In contrast, levels of the neurotoxic thiol homocysteine increased in a dose-dependent manner to IL-1β and TNF-α-induced activation. Our results suggest that chronically activated astrocytes in the brain might fail to adequately maintain GSH substrate delivery to neurons, thus promoting neuronal vulnerability. They might also explain the elevated levels of homocysteine found in the brains and serum of patients with AD.     

Analysis of Influence of Baicalin Joint Resveratrol Retention Enema on the TNF-α, SIgA,IL-2, IFN-γ of Rats with Respiratory Syncytial Virus Infection

Explore the influence of baicalin joint resveratrol retention enema on TNF-α, SIgA, IL-2, and IFN-γ of rats with respiratory syncytial virus (RSV) infection. The 60 SD rats were randomly divided into normal group, model group, baicalin group, resveratrol group, joint group, and ribavirin group. For model group, baicalin group, resveratrol group, joint group, and ribavirin group, rats were given RSV virus suspension intranasally for 3 days, and model group was not given administration. Baicalin group, resveratrol group, joint group, and ribavirin group were, respectively, given baicalin 100 mg/kg/day, resveratrol 30 mg/kg/day, baicalin joint resveratrol, and ribavirin 1 g/kg/day retention enema. After continuously given administration 7 days, rats were measured in serum TNF-α, IL-2, IFN-γ levels and SIgA levels in bronchoalveolar lavage fluid. Model group, TNF-α, IL-2, IFN-γ, and SIgA were significantly higher than the normal group (P < 0.05); Baicalin group, resveratrol group, ribavirin group, TNF-α, IL-2, IFN-γ, and SIgA were significantly higher than the model group (P < 0.05); TNF-α, IL-2 between baicalin group, resveratrol group, ribavirin group, have no significant difference (P > 0.05); Baicalin group, resveratrol group, joint group, IFN-γ, and SIgA were significantly higher than the ribavirin group (P < 0.05); Joint group TNF-α, IL-2, IFN-γ, and SIgA were significantly higher than baicalin group, resveratrol group, and ribavirin group (P < 0.05). Baicalin joint resveratrol retention enema can increase RSV infection model in rats serum TNF-α, IL-2, IFN-γ levels and SIgA levels in bronchoalveolar lavage fluid, which may anti-virus through this mechanism.     

The influences of sleep duration,chronotype, and nightwork on the ovarian cycle

ABSTRACT

Despite research indicating that sleep disorders influence reproductive health, the effects of sleep on reproductive hormone concentrations are poorly characterized. We prospectively followed 259 regularly menstruating women across one to two menstrual cycles (the BioCycle Study, 2005–2007), measuring fasting serum hormone concentrations up to eight times per cycle. Women provided information about daily sleep in diaries and chronotype and night/shift work on a baseline questionnaire. We evaluated percent differences in mean hormone concentrations, the magnitude of shifts in the timing and amplitude of hormone peaks, and the risk for sporadic anovulation associated with self-reported sleep patterns and night/shift work. We estimated chronotype scores – categorizing women below and above the interquartile range (IQR) as “morning” and “evening” chronotypes, respectively. For every hour increase in daily sleep duration, mean estradiol concentrations increased by 3.9% (95% confidence interval [CI] 2.0, 5.9%) and luteal phase progesterone by 9.4% (CI 4.0, 15.2%). Receiving less than 7 hours of sleep per day was associated with slightly earlier rises in peak levels for several hormones. Women reporting night/shift work (n = 77) had lower testosterone relative to women employed without night/shift work (percent difference: ?9.9%, CI ?18.4, ?0.4%). Women with morning chronotypes (n = 47) had earlier rises in estradiol during their cycles and potentially an earlier rise in luteinizing hormone. Compared to those who had intermediate chronotypes, women with evening chronotypes (n = 42) had a later luteinizing hormone peak of borderline statistical significance. A reduced risk for sporadic anovulation was suggested, but imprecise, for increasing hours of daily sleep leading up to ovulation (risk ratio 0.79, CI 0.59, 1.06), while an imprecise increased risk was observed for women with morning chronotypes (risk ratio 2.50, CI 0.93, 6.77). Sleep-related hormonal changes may not greatly alter ovarian function in healthy women, but have the potential to influence gynecologic health.     

腹部外伤患者术后感染与血清炎症因子的关联性研究

本研究旨在探讨外伤术后腹腔感染患者血清降钙素原(PCT)、肿瘤坏死因子-α(TNF-α)、C-反应蛋白(CRP)和白细胞介素6 (IL-6)的水平变化与感染程度的相关性,为外伤术后腹腔感染临床治疗、抗菌药物应用提供依据。本研究选取我院2015年1月至2017年5月收治的腹部外伤手术患者150例,其中术后发生感染患者83例,未感染组,未发生感染患者67例,为非感染组。通过检测其术前术后及进行抗感染治疗后的PCT、TNF-α、CRP、IL-6水平,对腹腔感染标本进行菌种鉴定,并分析PCT、TNF-α、CRP、IL-6水平变化与腹腔感染的相关性,本研究发现,感染组患者术后各时间段血清PCT、TNF-α、CRP、IL-6水平明显较术前升高(p<0.05);且在术后12 h、24 h、72 h的PCT、TNF-α、CRP、IL-6水平明显高于未感染组(p<0.05);感染患者标本共检出76株不同的菌株,革兰阴性杆菌45株,革兰阳性菌22株,真菌9株;PCT、TNF-α、CRP在术后12 h、24 h、72 h检出感染的阳性率与病原学诊断结果相关性较高,血清IL-6则在术后72 h检出感染的阳性与病原学诊断相关性较高。本研究初步得出结论,临床检测血清PCT、TNF-α、CRP和IL-6均有助于鉴别是否存在外科腹腔感染,对抗菌药物的应用有一定的指导作用。     

Peritoneal cytokines as early markers of peritonitis following surgery for colorectal carcinoma: a prospective study

This study was to investigate if measurement of peritoneal cytokines is valuable for an early diagnosis of peritonitis following colorectal surgery. One hundred consecutive patients who were to undergo elective resection for carcinoma of the sigmoid colon or the rectum were investigated. Abdominal exudate was obtained from a drainage tube daily after surgery for measuring interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α. The relationship between peritoneal cytokine levels during the first 3 days after surgery and the development of peritonitis was investigated. Eight patients developed postoperative peritonitis due to anastomotic leakage and pelvic abscess, which was diagnosed on postoperative days 5-8. Peritoneal cytokine levels on postoperative days 1 and 2 were not significantly different between the 8 patients who developed peritonitis and 92 patients who did not: day 1, IL-1βP=0.32, IL-6 P=0.45, TNF-αP=0.85; day 2, IL-1βP=0.26, IL-6 P=0.68, TNF-αP=0.22. In contrast, the cytokine levels on day 3 were significantly higher in patients who developed peritonitis as compared with patients who did not: IL-1βP=0.008, IL-6 P<0.0001, TNF-αP=0.0001. The cytokines significantly increased during the first 3 days in patients who developed peritonitis: IL-1βP=0.049, IL-6 P=0.03, TNF-αP=0.01, while significantly decreased in patients who did not: IL-1βP<0.0001, IL-6 P<0.0001, TNF-αP<0.0001. The outcomes of this investigation showed that the rise in peritoneal IL-1β, IL-6 and TNF-α levels may be an additional early diagnostic predictor of intraabdominal complications following colorectal surgery.     

Expression of HAb18G in non-small lung cancer and characterization of activation, migration, proliferation, and apoptosis in A549 cells following siRNA-induced downregulation of HAb18G

VSL#3 probiotics can be effective on induction and maintenance of the remission of clinical ulcerative colitis. However, the mechanisms are not fully understood. The aim of this study was to examine the effects of VSL#3 probiotics on dextran sulfate sodium (DSS)-induced colitis in rats. Acute colitis was induced by administration of DSS 3.5 % for 7 days in rats. Rats in two groups were treated with either 15 mg VSL#3 or placebo via gastric tube once daily after induction of colitis; rats in other two groups were treated with either the wortmannin (1 mg/kg) via intraperitoneal injection or the wortmannin + VSL#3 after induction of colitis. Anti-inflammatory activity was assessed by myeloperoxidase (MPO) activity. Expression of inflammatory related mediators (iNOS, COX-2, NF-κB, Akt, and p-Akt) and cytokines (TNF-α, IL-6, and IL-10) in colonic tissue were assessed. TNF-α, IL-6, and IL-10 serum levels were also measured. Our results demonstrated that VSL#3 and wortmannin have anti-inflammatory properties by the reduced disease activity index and MPO activity. In addition, administration of VSL#3 and wortmannin for 7 days resulted in a decrease of iNOS, COX-2, NF-κB, TNF-α, IL-6, and p-Akt and an increase of IL-10 expression in colonic tissue. At the same time, administration of VSL#3 and wortmannin resulted in a decrease of TNF-α and IL-6 and an increase of IL-10 serum levels. VSL#3 probiotics therapy exerts the anti-inflammatory activity in rat model of DSS-induced colitis by inhibiting PI3K/Akt and NF-κB pathway.     

丁苯酞对睡眠剥夺大鼠额叶小胶质细胞活化的影响*

目的: 探讨丁苯酞对慢性睡眠剥夺后大鼠脑部额叶小胶质细胞活化及炎症因子的影响。方法: 本实验共分为4组(n＝8):空白对照组、大平台对照组、慢性睡眠剥夺组、丁苯酞干预组。慢性睡眠剥夺组和丁苯酞干预组采用改良多平台睡眠剥夺法建立大鼠慢性睡眠剥夺模型,对大鼠进行每日18 h,连续28 d的睡眠剥夺。在这28 d内,空白对照组大鼠不进行睡眠干预,大平台对照组大鼠放于大平台箱内。丁苯酞干预组在睡眠剥夺28 d结束后按100 mg/kg腹腔注射丁苯酞针剂,每日1次,共14 d,其他组大鼠在这14 d内腹腔注射同样剂量的生理盐水。腹腔注射结束后各组大鼠取脑组织,免疫组化检测额叶皮质离子钙接头分子(Iba-1)阳性细胞并计数,Western blot检测额叶诱导型一氧化氮合成酶(iNOS)、精氨酸酶1(Arg1)表达,实时定量PCR检测额叶白介素-1(IL-1)mRNA、IL-6 mRNA、肿瘤坏死因子-α(TNF-α) mRNA。结果: 与空白对照组、大平台对照组比较,慢性睡眠剥夺组额叶Iba-1阳性细胞体积增大伴细胞突起增多,且细胞数增加(P均＜0.05),iNOS和IL-1 mRNA、IL-6 mRNA、TNF-α mRNA表达增加,而Arg1表达减少(P均＜0.05);与慢性睡眠剥夺组比较,丁苯酞干预组额叶Iba-1细胞数减少(P＜ 0.05),iNOS和IL-1 mRNA、IL-6 mRNA、TNF-α mRNA表达减少(P均＜0.05)而Arg1表达无明显改变。结论: 丁苯酞可抑制慢性睡眠剥夺导致的大鼠额叶小胶质细胞活化、减少慢性睡眠剥夺后的炎症因子表达。     

Polymorphisms in the TNF-α and IL-10 gene promoters and risk of psoriasis and correlation with disease severity

Several cytokines were assumed to play an essential role in the induction and the pathogenesis of psoriasis. The aim of this work was to investigate the role of TNF-α-308 and IL-10-1082 polymorphisms and their serum levels in the pathogenesis of psoriasis and determine their relation to disease severity. 110 Psoriasis patients and 120 healthy volunteers were genotyped for TNF-α-308 and IL-10-1082 polymorphism by polymerase chain reaction. Serum level of TNF-α and IL-10 were measured by ELISA. Our study demonstrated an association of IL-10-1082 polymorphism and psoriasis and between TNF α-308 polymorphism and psoriasis disease and severity. Serum TNF α increased in patients, while serum IL-10 decreased in patients with significant correlation between serum TNF-α and psoriasis severity. These results indicated that TNF-α-308 and IL-10-1082 polymorphisms imparted significant risk towards the development of psoriasis.     

慢性肾小球肾炎患者治疗前后血清CRP和VEGF浓度变化及临床意义

目的：研究慢性肾小球肾炎（CNG）中血清C反应蛋白（CRP）和血管内皮生长因子（VEGF）的浓度变化及其临床意义。方法：采用ELISA法测定35例正常对照组与41例慢性肾小球肾炎患者治疗前后血清IL-6和VEGF的浓度,同时放射免疫分析法测定血清TNF-α浓度,免疫比浊法测定血清CRP与尿Alb浓度。结果：①治疗前后CNG患者血清中IL-6、TNF-α和CRP较正常对照组均显著升高（P〈0.05或P〈0.01）,但治疗后IL-6、TNF-α和CRP水平显著低于治疗前（P〈0.01）,且血清CRP与IL-6和TNF-α呈正相关（P〈0.01）。②治疗后,CNG患者血清VEGF水平与尿Alb含量较治疗前明显降低（P〈0.05或P〈0.01）,仍显著高于正常对照组（P〈0.05或P〈0.01）,且血清VEGF与尿Alb水平呈正相关（P〈0.01）。结论：CRP、IL-6和TNF-α参与了CNG患者慢性炎症反应,VEGF则与蛋白尿的产生密切相关,治疗前后血清CRP和VEGF检测对于慢性肾小球肾炎的病情了解及临床疗效评估均具有重要的临床价值。