Peripheral blood mononuclear cell proliferative responses to soluble and particulate heat shock protein 65 in health and inflammatory bowel disease

Objectives: The aims of this study were to determine, in peripheral blood mononuclear cells (PBMC), whether particulate antigen triggers (i) an amplified cell proliferative response compared to soluble antigen and (ii) a dysfunctional response in cells derived from patients with chronic inflammation and specifically in those with inflammatory bowel disease (IBD). Subjects: Healthy volunteers (n = 17), inflammatory controls (n = 8) and patients with IBD (n = 17) were recruited from St Thomas’ and Guys’ Hospital, London, UK. Methods: Following optimisation of experimental conditions (0.1–10.0 μg/ml antigen), PBMC were stimulated with (i) 10.0 μg/ml recombinant soluble heat shock protein 65 (hsp 65) and (ii) 1.0 and 10.0 μg/ml hsp 65 conjugated to microparticles (0.5 μm diameter). PBMC proliferative responses were measured by ³H-Thymidine incorporation at day 5 and results compared between groups using unpaired t-test. Results: Conjugation to microparticles of low dose hsp 65 significantly increased overall proliferative responses by 2–11 fold compared to soluble antigen alone (p < 0.05). However, no specific PBMC proliferative dysregulation was noted in cells from subjects with IBD. Conclusions: Low dose antigen, in microparticulate form, leads to amplified cell proliferation in primary human cells, as showed previously in cell lines and animal studies. However there is no abnormal proliferative response in cells from subjects with IBD. Received 8 February 2006; returned for revision 7 March 2006; accepted by G. Wallace 25 October 2006     

Thermal tolerance following artificially induced polycythaemia

Polycythaemia has been shown to improve physical performance, possibly due to increased arterial oxygen transport. Enhanced thermoregulatory function may also accompany this manipulation, since a greater proportion of the cardiac output becomes available for heat dissipation. We further examined this possibility in five trained men, who participated in three-phase heat stress trials (20 min rest, 20 min cycling at 30% peak power W_peak and 20 min at 45% W_peak at 38.3 (SEM 0.7)°C [relative humidity 41.4 (SEM 2.9)%]. Trials were performed during normocythaemia (control) and polycythaemia, obtained by reinfusion of autologous red blood cells and resulting in significant elevation of arterial oxygen transport. During the polycythaemic trials, the subjects demonstrated diminished thermal strain, as evidenced by a significant reduction in cardiac frequency (f _c: 12 beats · min^–1 lower throughout the test;P < 0.05), and reduced auditory canal temperatures (T _ae) during the latter 20-min phase (P < 0.05). Forearm sweat onset was more rapid (363.0 compared to 1083.0 s;P < 0.05), and forearm sweat rate (. _msw) sensitivity was elevated from 1.80 to 2.91 · mg · cm^–2 · min^–1 · °C^–1 (P < 0.05). Foreheadm _sw was depressed during the final 20 min, while forearmm _sw was greater during all test phases, averaging 0.94 and 1.20 mg · cm^–2 · min^–1, respectively, over the 60 min. Skin blood flows for the upper back, upper arm and forearm were reduced (P < 0.05). Polycythaemia enhanced thermoregulation, through an elevation in forearm sweat sensitivity and.m _sw, but not via increased cutaneous blood flow. These modifications occurred simultaneously with decreases inf _c andT _ae, resulting in greater thermal tolerance.     

热休克蛋白70对小鼠海马CA3 区神经元损伤的保护作用

目的:探讨心理应激对海马CA3区神经元凋亡的影响,热休克蛋白70(Hsp70)对心理应激引起的海马CA3区神经元凋亡的保护作用。方法:建立心理应激、热应激(Heat Shock Pretreatment)、心理应激加热应激三种动物模型,利用免疫组化和TUNEL分别检测海马CA3区神经元在第1、2、3个月三个时间段的Hsp70表达和神经元凋亡水平。结果:有心理应激的各组动物海马凋亡神经元数高对照组(P<0·05),热应激加心理应激组凋亡神经元在2、3个月时较同时段心理应激组下降(P<0·05),但热应激组与对照组间差异没有显著性。有热应激各组Hsp70表达数高于无热应激的两组(P<0·01)。海马CA3区Hsp70表达水平与神经元调亡水平呈负相关(r=-0·26,P=0·03)。结论:热应激可促进海马Hsp70的表达,热休克蛋白70对心理应激导致的海马CA3区神经元损伤有保护作用。     

Reduced thirst in old, thermally dehydrated rats

Water intake and blood parameters of young (7-month) and old (23-month) male Brown Norway rats were assessed following a period of thermal dehydration. Rats of both ages were randomly assigned to one of three groups: (1) Unheated-blood sample, (2) Heated-blood sample, and (3) Heated-water intake. The colonic temperature of heated rats was raised at the rate of 0.05 degrees C/min for 1 h using an infrared heat lamp. Water intake was then measured over the following 2 h. The heating protocol resulted in a similar level of dehydration in both young and old rats; however, plasma osmolality and sodium concentration increased to a significant extent only in the young rats. Old rats drank significantly less water at all time points during the 2 h following the heat stress. While neither group replaced the water lost as a result of the thermal dehydration, the young rats did rehydrate to a greater extent. These results suggest that the diminished level of rehydration in aged rats, following a thermal dehydration, is due to an attenuated rise in plasma osmolality.     

睡眠剥夺对HSP70表达及脑超微结构的影响

目的：观察睡眠剥夺（SD）后大鼠脑组织HSP70表达的变化及对超微结构的影响。方法：44只雄性SD大鼠随机分为11组，每组4只，免疫组织化学方法检测HSP70的表达，电镜观察海马超微结构的变化。结果：睡眠剥夺后12小时即可在大脑皮质及海马观察到HSP70阳性细胞，2—3天数量达到高峰，7天时明显下降。白天睡眠剥夺12小时（SDd12h）组HSP70阳性细胞数较夜晚睡眠剥夺12小时（SDn12h）组多（P〈0．05）。RS组大脑皮质HSP70阳性细胞数较白天睡眠剥夺1天（SDd1d）组减少（P〈0．05）。白天睡眠剥夺3天（SDd3d）海马出现超微结构改变，白天睡眠剥夺7天（SDd7d）后改变更加明显。结论：睡眠剥夺可影响大鼠脑组织HSP70表达及超微结构。     

热休克蛋白70对离体心脏心肌间质的保护作用

目的探讨热休克蛋白70（HSP70）对大鼠离体心脏心肌间质的影响。方法Wistar大鼠16只，分为2组：对照组（C，n=8），腹腔注射生理盐水0．4ml，24h后取离体心脏灌注HTK心脏保护液，4℃保存3h后建立Langendorff灌注模型，灌注KH液2h；实验组（E，n=8），腹腔注射重酒石酸去甲肾上腺素，24h后取离体心脏，方法同对照组。以心肌细胞中HSP70含量、血流动力学指标、心肌组织羟脯氨酸（HP）、内皮索（ET）含量和心肌超微结构等作为观察指标。结果HSP70含量E组与C组比较明显增高；E组心功能恢复方面优于C组（P〈0．05），HP含量优于C组（P〈0．01），ET含量低于C组（P〈0．01），心肌超微结构损伤较C组明显减轻。结论HSP 70对供心心肌间质具有保护作用。     

The effect of postural changes on body temperatures and heat balance

Early studies have demonstrated that rectal temperature (T _re) decreases and mean skin temperature (T _sk) increases in subjects changing their posture from standing to supine, and vice versa. Such changes have important implications insofar as thermal stress experiments are conducted and interpreted. However, the extent of these changes between steady-state conditions is not known. In addition, it is not known whether thermal balance is also affected by postural changes. To examine these questions, 11 healthy males were exposed to a thermoneutral air environment (28.2–28.5°C and 40% relative humidity) in various postures at rest. Body temperatures, heat losses, and metabolic rate were measured. Subjects wore shorts only and began in an upright posture (standing or sitting at an inclination of 7.5°) on a customized tilt-table. They were tilted twice, once into a supine position and then back to the original upright position. Each tilt occurred after steady state was satisfied based on the subject's circadian variation of T _re determined previously in a 4.25 h control supine trial. Times to supine steady state following the first tilt were [mean (SE)] 92.6 (6.4) and 116.6 (5.1) min for the standing and sitting trials, respectively. Times to upright steady state following the second tilt were 107.9 (11.4) and 124.1 (9.0) min. Mean steady-state T _re and T _sk were 36.87 (0.07) and 34.04 (0.14), 37.47 (0.09) and 33.48 (0.14), and 37.26 (0.05) and 33.49 (0.10) °C for supine, standing, and sitting, respectively. Thermal balance was attained in all steady-state conditions, and allowing for a decrease in the weighting factor of T _re for mean body temperature in the upright postures, it also appears that thermal balance was preserved between changes in posture. These results are consistent with no perceived changes by the subjects in their thermal comfort and skin wetness.     

Hyperthermia and maximal oxygen uptake in men and women

To compare the effect of hyperthermia on maximal oxygen uptake (O_2max) in men and women, O_2max was measured in 11 male and 11 female runners under seven conditions involving various ambient temperatures (T_a at 50% RH) and preheating designed to manipulate the esophageal (T_es) and mean skin temperatures at O_2max. The conditions were: 25°C, no preheating (control); 25, 35, 40, and 45°C, with exercise-induced preheating by a 20-min walk at ~33% of control O_2max; 45°C, no preheating; and 45°C, with passive preheating during which T_es and were increased to the same degree as at the end of the 20-min walk at 45°C. Compared to O_2max (l·min^–1) in the control condition (4.52±0.46 in men, 3.01±0.45 in women), O_2max in men and women was reduced with exercise-induced or passive preheating and increased T_a, ~4% at 35°C, ~9% at 40°C and ~18% at 45°C. Percentage reductions (7–36%) in physical performance (treadmill test time to exhaustion) were strongly related to reductions in O_2max (r=0.82–0.84). The effects of hyperthermia on O_2max and physical performance in men and women were almost identical. We conclude that men and women do not differ in their thermal responses to maximal exercise, or in the relationship of hyperthermia to reductions in O_2max and physical performance at high temperature. Data are reported as mean (SD) unless otherwise stated.     

Direct measurement of the thermal responses of nude resting men in dry environments

Summary Two nude resting men were exposed for two-hour periods to each of 25 dry environments, with air temperatures ranging between 12.8° C and 49.1° C and wind speeds between 0.67 m/sec and 4.94 m/sec. The mean radiant temperature of the surroundings was kept equal to the air temperature. Rates of radiant and convective heat exchange were measured directly, separately and continuously. The men had reached a thermal steady state after 105 min in the warm environments, but not in the cold environments. Graphs are presented to show the effect of ambient temperature and wind speed on the radiation and convection rates attained after 105 min, as well as on metabolic rate, sweat evaporation rate, rectal temperature and mean skin temperature. These graphs revealed some important aspects of the behaviour of man's thermal control system. In particular the physiological conductance increased with increasing ambient temperature and then saturated at an ambient temperature near 35° C. This saturation resulted in a constant difference between rectal temperature and mean skin temperature irrespective of the environmental conditions.Published with the permission of the Chamber of Mines of South Africa.