Cytokine content in lymphoid and white adipose tissues after repeated CpG oligodeoxynucleotide administration in trained rats.

The increased threat of bioterrorism and the emergence of potentially fatal diseases underscores the need to improve treatments for protecting all segments of the human population including military personnel. New methods need to be developed. The ability of oligodeoxynucleotides containing the CpG motif (CpG ODNs) to promote the production of T(H)1-type pro-inflammatory cytokines suggest they might be useful as vaccine adjuvants, but their potential effects during exercise have not been widely studied. Repeated administration of CpG ODN in sedentary rats promoted the production of T(H)1-type pro-inflammatory cytokines in spleen, Peyer's patches and adipose tissues. However, such an increase was not observed in trained rats, suggesting that CpG would not be the best agent for vaccine adjuvants and immunomodulation in intensely trained rats.

Effect of a probiotics supplementation on respiratory infections and immune and hormonal parameters during intense military training.

This study examined the effect of a probiotics supplementation on respiratory tract infection (RTI) and immune and hormonal changes during the French Commando training (3-week training followed by a 5-day combat course). Cadets (21 +/- 0.4 years) received either a probiotics (n = 24) or a placebo (n = 23) supplementation over the training period. We found no difference in the RTI incidence between groups but a significantly greater proportion of rhinopharyngitis in the probiotic group (p < 0.05). Among immune parameters, the major finding was an immunoglobulin A decrease after the combat course only in the placebo group (p < 0.01), but the difference between the two groups was not significant. A greater increase in dehydroepiandrostane sulfate was observed in the probiotics group after the combat course (p < 0.05). This study suggested that the benefits of a probiotics supplementation in a multistressor environment relied mainly on its capacity to prevent the infection to spread throughout the respiratory tract.

Comparison of systemic cytokine responses after a long distance triathlon and a 100-km run: relationship to metabolic and inflammatory processes.

Suggested mechanisms for the systemic, circulating cytokinemia observed during heavy physical exertion include inflammation and energy demand. We compared cytokine levels and examined the underlying physiological mechanisms between a long-distance triathlon and a 100-km run, two endurance races of similar duration but characterized by differences in muscle strain. Blood samples were collected from 12 triathletes (34.8 +/- 1.4 yr) and 11 runners (42.4 +/- 2.2 yr) the day before and at the end of races (T1, R1), and 24 h and 7 days post-race (R2, R3). At R1, significant race-related differences were observed, with greater increases in plasma levels of interleukins (IL)-6, IL-1ra, and IL-10 in the triathletes than in the runners, while levels of the chemokine IL-8 increased solely in the runners (P < 0.05, P < 0.05, P < 0.01, and P < 0.001, respectively). At R1, free fatty acid (FFA) levels were 119% higher in the triathletes than in the runners, who were the most liable to muscle damage in view of increased levels of the muscle-specific enzyme, creatine kinase (CK), loss of muscle flexibility and decreased physical performance. At R1, levels of heat shock protein (HSP)72 increased in the two groups but were 173% higher in the runners. For the two groups, all parameters had returned to pre-race levels by seven days post-race. Positive correlations were noted between IL-6 and FFA in the triathletes and between IL-8 and CK and HSP72 in the runners. The differences between cytokine responses after a long distance triathlon and a 100-km run suggested that IL-6 and IL-8 could be employed as respective markers of the intensity of the muscular activity required for substrate availability and vascular inflammation.

Influence of a high carbohydrate diet on the functional activity of 5-HT1B/1D receptors on human peripheral blood lymphocytes during intense military training.

The present study was undertaken to examine the effect of a high carbohydrate diet on the functional activity of 5-HT1B/1D receptors in human peripheral blood lymphocytes, and on serum cortisol and plasma cytokine responses during intense military training. Thirty two male soldiers (mean age: 21 +/- 2 years) were randomly assigned to two groups and received either 3200 kcal/24 h [13440 kJ; habitual diet group (HD)] or 4200 kcal/24 h [17640 kJ, high carbohydrate diet group (HCD)] by adding 1000 kcal (4200 kJ) of fruit jelly to the HD. They took part in a three-week training program followed by a five-day combat course. Blood samples were collected from each group before entry into the commando training and after the five-day combat course. The results of [35S] GTPgammaS binding assays showed that h5-HT1B/1D receptors were desensitized after the training program in the HD group, whereas no change was observed between the beginning and the end of the military training in the HCD group [(HD : IC50 = 100 +/- 14 nM to 544 +/- 178 nM; n = 16) and (HCD: IC50 = 68 +/- 14 nM to 101 +/- 22 nM; n = 16)]. Serum cortisol was only significantly increased after the commando training in the HD group (from 532.2 +/- 30 to 642 +/- 45 nmol.L(-1), p < 0.05), whereas values were not significantly changed in the HCD group (441 +/- 31 to 502 +/- 40 nmol.L(-1)). No changes were observed in IL-10, TNF-alpha and IFN-gamma levels after the training program in either group. Carbohydrate ingestion or additional dietary energy during repeated bouts of high-intensity exercise could attenuate the alterations in immune function via 5-HT1B/1D receptors and the action of 5-HT moduline, an endogenous tetrapeptide (Leu-Ser-Ala-Leu) that specifically modulates the sensitivity of 5-HT1B/1D receptors.

Aerobatic flight effects on baroreflex sensitivity and sympathovagal balance in experienced pilots.

BACKGROUND: Aerobatic flights subject pilots to accelerations and, therefore, to heavy physical workloads. OBJECTIVE: Our aim was to document changes in spontaneous baroreflex sensitivity and disturbances of sympathovagal balance after exposure to "push-pull" accelerations. METHODS: During 30-min flights, five aerobatic pilots performed five series of descending spirals: first, 30 s under negative (-3 Gz max), and then 30 s under positive (+4 Gz max) G loading, climbing between each series to regain altitude. A stand-test was performed before (T0), immediately postflight (PF), 1 h (PF1), and 2 h after (PF2) the flight. A Finapres apparatus recorded heart rate (HR) and BP during the stand-tests. RESULTS: Resting HR was higher at PF than T0 in supine (11.2 +/- 5.3%, p < 0.01) and standing (11.0 +/- 4.9%; p < 0.05) positions. Sequence analysis of spontaneous baroflex sensitivity (BRS) and spectral analysis of HR variability showed that: a) supine spontaneous BRS did not differ between preflight and postflight, while parasympathetic modulation of HR variability tended to increase; and b) supine spontaneous BRS was higher at PF1 than PF (PF: 0.011 +/- 0.0014 ms x mmHg(-1), PF1: 0.015 +/- 0.0012 ms x mmHg(-1); p < 0.05) and parasympathetic modulation of HR variability (high frequency component) was higher at PF2 than PF (PF: 0.014 +/- 0.007, PF2: 0.039 +/- 0.009; p < 0.001). CONCLUSIONS: These findings may reflect a change in the sympathovagal balance during the second hour of recovery from repeated push-pull maneuvers.

Effects of combined stress during intense training on cellular immunity, hormones and respiratory infections.

OBJECTIVES: This study was designed to determine immune and hormonal changes and their relationship with the incidence of upper respiratory tract infections (URTIs) during an extremely stressful military training (3 weeks of physical conditioning followed by a 5-day combat course with energy restriction, sleep deprivation and psychological stress). METHODS: Blood samples were collected from 21 cadets (21 +/- 2 years old) before training and after the combat course for analysis of leukocyte and lymphocyte subpopulations, serum cytokines [interleukin-6 (IL-6), IL-1beta and IL-10], and hormones [catecholamines, cortisol, leptin, total insulin-like growth factor I (IGF-I), prolactin, dehydroepiandrosterone sulfate (DHEAS) and testosterone]. Symptoms of URTI were recorded from health logs and medical examinations during training. RESULTS: After the combat course, total leukocyte and neutrophil counts were significantly increased while total lymphocytes were unchanged. In lymphocyte subsets, NK cells were reduced (p < 0.01), while CD4+ and CD19+ (B) cells were increased. Levels of IL-6 were increased (p < 0.01), while those of IL-1beta and IL-10 were unchanged. Norepinephrine and dopamine levels were increased, while those of cortisol were reduced. Levels of leptin, testosterone, prolactin and total IGF-I were reduced, while those of DHEAS were increased. The incidence of URTI increased during the training (chi(2) = 53.48, p < 0.05). After training data analysis showed a significant correlation between URTIs and NK cells (p = 0.0023). Training-induced changes in immune and hormonal parameters were correlated. CONCLUSIONS: Blood NK cell levels are related to increased respiratory infections during physical training in a multistressor environment. The training-induced decreases in immunostimulatory hormone levels may have triggered immunosuppression.

EEG and ECG changes during simulator operation reflect mental workload and vigilance.

BACKGROUND: Performing mission tasks in a simulator influences many neurophysiological measures. Quantitative assessments of electroencephalography (EEG) and electrocardiography (ECG) have made it possible to develop indicators of mental workload and to estimate relative physiological responses to cognitive requirements. OBJECTIVE: To evaluate the effects of mental workload without actual physical risk, we studied the cortical and cardiovascular changes that occurred during simulated flight. METHODS: There were 12 pilots (8 novices and 4 experts) who simulated a flight composed of 10 sequences that induced several different mental workload levels. EEG was recorded at 12 electrode sites during rest and flight sequences; ECG activity was also recorded. Subjective tests were used to evaluate anxiety and vigilance levels. RESULTS: Theta band activity was lower during the two simulated flight rest sequences than during visual and instrument flight sequences at central, parietal, and occipital sites (p < 0.05). On the other hand, rest sequences resulted in higher beta (at the C4 site; p < 0.05) and gamma (at the central, parietal, and occipital sites; p < 0.05) power than active segments. The mean heart rate (HR) was not significantly different during any simulated flight sequence, but HR was lower for expert subjects than for novices. The subjective tests revealed no significant anxiety and high values for vigilance levels before and during flight. CONCLUSIONS: The different flight sequences performed on the simulator resulted in electrophysiological changes that expressed variations in mental workload. These results corroborate those found during study of real flights, particularly during sequences requiring the heaviest mental workload.

Cerebral oxygenation declines despite maintained orthostatic tolerance after brief exposure to gravitational stress.

We examined the effect of a single 120 s of exposure to +3Gz (head-to-foot inertial forces) centrifugation as orthostatic stress on cerebral oxygenation (oxy-Hb) and cerebral blood volume (CBV) changes in response to stand test, in order to relate the occurrence of altered cerebral oxygenation control to any increase in sympathetic activity. Frontal near-infrared spectroscopy and mean arterial blood pressure at brain level (MAPbrain) were recorded in 14 subjects in supine and then in standing (10 min) position, before and after +3Gz centrifugation. The decrease in oxy-Hb (-7 +/- 5 a.u. versus -27 +/- 4 a.u., P<0.001) and in CBV (-6 +/- 10 a.u. versus -15 +/- 8 a.u., P<0.05) upon standing was more important after +3Gz centrifugation, with unchanged MAPbrain (-8 +/- 8 mmHg versus -3 +/- 11 mmHg). Upon standing, the high-frequency component of heart rate was lower (1090 +/- 460 ms2 versus 827 +/- 412 ms2, P<0.05) after +3Gz centrifugation. These findings suggest a downward shift in the static cerebral autoregulatory curve. We conclude that cerebral vasoconstriction might have occurred without centrally mediated increase in the entire peripheral sympathetic activity of the body.

EEG and ECG changes during selected flight sequences.

BACKGROUND: Mental workload has become a critical factor in the design and use of modern aircraft. Because of the complexity of the human-machine system, it is necessary to determine workload, fatigue, and level of performance using noninvasive electrophysiological measures. OBJECTIVE: Our objective was to identify the electrophysiological indicators of mental workload during piloting tasks. METHODS: Electroencephalographic (EEG) and electrocardiographic (ECG) activity was recorded during actual flight, with a profile planned to produce different levels of mental workload. RESULTS: In-flight EEG and ECG recordings enabled us to document mental workload levels. During active segments, delta and theta band activity increased (p < 0.05 or greater); results showed an increase of 22.5% for theta band activity during active flight segments compared with in-flight rest periods. Inversely, alpha band activity diminished: the decrease between ground baseline and all flight sequences was 30% (p < 0.05 or greater). These variations were reversed during the in-flight rest sequences. Instrumental flight caused an increase in the theta and alpha frequency band activity in the parietal-occipital area (p < 0.05 or greater); the alpha/beta ratio also increased. Heart rate increased during the active segments and fell during the in-flight rest periods. The mean difference between active segments and in-flight rest periods was of 8.89 bpm (i.e., an increase of 11.5%; p < 0.01). Heart rate was correlated to the EEG activity of the delta and beta bands in the central area (C3, Cz, C4, p < 0.05). CONCLUSIONS: The electrophysiological measures recorded provide useful indicators of the mental workload required by different flight sequences.

Analysis of heart rate variability after a ranger training course.

We studied the effects of prolonged physical activities on resting heart rate variability (HRV) during a training session attended by 23 cadets of the French military academy. This course lasts 1 month and is concluded by a 5-day field exercise simulation with physical and psychological stress. Data collection took place before (B) and immediately at the end (E) of the course. It included HRV recordings during a stand test (5 minutes lying down and 5 minutes standing), with a Polar R-R monitor, followed by blood sampling to assay plasma testosterone. The results (B and E) showed that the testosterone level fell by approximately 28.6 +/- 7%, indicating a high level of fatigue. During the stand test, the total power (TP) of the HRV spectrum increased in a supine position. The TP of B was 5,515.7 ms2 (SE, 718.4) and of E was 13018.9 ms2 (SE, 2,539.2; p < 0.001). High-frequency (HF) normalized values increased and low-frequency (LF) normalized values fell, regardless of position (HF normalized values and LF normalized values: supine, p < 0.01, p < 0.05; standing, p < 0.05, p < 0.01, respectively). LF:HF ratio fell 66.2 (SE, 12.9%; p < 0.01) in a lying position. During the time-domain analysis of HRV, differences between adjacent normal R-R intervals more than 50 milliseconds, expressed as a percentage, and differences between the coupling intervals of adjacent normal RR intervals increased in the lying position (p < 0.001). These results as a whole suggest that parasympathetic nervous system activity increases with fatigue.

Leptin, catecholamines and free fatty acids related to reduced recovery delays after training.

The aim of this study was to observe the effects of exercise on plasma free fatty acids (FFA), the catecholamines (adrenaline, noradrenaline, dopamine) and leptin levels, before and after training, to determine their possible influence on the improvement of the regulation of energy homeostasis. Eleven trained rowers performed two exercise sessions (S1, S2) of 90 min each (70-75% V(.)O(2peak)), separated by a 36-week period of intense endurance training. Leptin, FFA and catecholamine plasma concentrations were measured both at the beginning and at the end of S1 and S2, and after recovery periods of 2 and 24 h. Training modified leptin levels in S2 as opposed to S1 ( P<0.001); in S1 leptin levels remained lower after a 24 h recovery whereas they returned to pre-exercise levels in S2. The respiratory exchange ratio was significantly reduced in S2 compared to S1 ( P=0.018). The FFA and leptin levels were correlated after a 24-h recovery in S1 ( r=0.87; P=0.0082), and after a 2-h recovery in S2 ( r=0.66; P=0.021). All data were expressed as the means and standard errors of the mean. In the two sessions, an immediate exercise effect was observed on the levels of the catecholamines, which did not persist after recovery. This training effect was apparent for all catecholamines in response to exercise, particularly on noradrenaline ( P=0.0006). The noradrenaline and leptin levels were correlated after a 2-h recovery in S2 ( r=-0.74; P=0.0042). We conclude that the effect of training on the response of noradrenaline to exercise seems to be involved in the delay in the normalization of leptin levels. We suggest that the amplitude of the noradrenaline response to exercise induced an increase in fat use and a rapid leptin recovery after exercise. The sensitivity of leptin to changes in the fat stores may be improved after training. Both training effects seemed to be involved in the reduction of the recovery time observed for the leptin levels.

Declarative memory impairments following a military combat course: parallel neuropsychological and biochemical investigations.

The aim of this study was to investigate the impact on several forms of memory and metabolism of a 5-day combat course including heavy and continuous physical activities and sleep deprivation. Mnemonic performance and biochemical parameters of 21 male soldiers were examined before and at the end of the course. Our results showed that short-term memory (memory span, visual memory, audiovisual association) and long-term memory were significantly impaired, whereas short-term spatial memory and planning tasks were spared. Parallel biochemical analysis showed an adaptation of energy metabolism. The observed decrease in glycaemia may be partly responsible for the long-term memory impairment, whereas the decreases in plasma cholinesterases and choline may be involved in the short-term memory deterioration. However, there are also many other reasons for the observed memory changes, one of them being chronic sleep deprivation.

Leptin response to acute prolonged exercise after training in rowers.

The aim of this study was to determine if there is a training effect on leptin levels at rest or after prolonged exercise during an 8-month training season of rowers. Eleven trained rowers were evaluated at three sessions (control, early and late) during the season. At the early and late sessions, leptin and insulin concentrations were measured before and after 90 min of rowing exercise (70-75% maximal oxygen consumption, VO(2)max), 120 min and 24 h afterwards. Anthropometrics data were collected at each session. Energy balance was determined on the days of exercise sessions. Resting leptin levels were not modified over the season and were in correlation with weight and body fat (P<0.05). At exercise sessions, a delayed reducing effect of acute exercise on leptin levels appeared ( P<0.01 compared to pre-exercise). After 24 h of recovery, leptin levels remained lower at early (P<0.001) but not at late sessions, and a training effect appeared between early and late sessions (P<0.001). Leptin levels were correlated with energy balance at early and late sessions (P<0.05). At the two training sessions, insulin levels were decreased immediately post-exercise and at 120 min of recovery compared to pre-exercise (P<0.01 and P<0.001 respectively for the two sessions). A training effect on insulin levels appeared at 24 h of recovery (P<0.05 between early and late sessions). We concluded that rowing training over a season did not alter resting leptin levels but it attenuated the exercise-induced reduction in leptin. This could be attributed to an alteration in energy balance, although an influence of training on insulin may also be involved in the leptin response to acute exercise.

[Overtraining syndrome]. / Le syndrome de surentraînement.

Numerous studies have shown that enhanced physical load can result in an overtraining syndrome, with a decreased capacity for physical exercise and behavioral disturbances. Overtraining is caused by an imbalance between energy intake and output, and is facilitated by chronobiological and psychological stress. These factors are responsible for hormonal changes such as a decrease in gonadal steroids or in the hypothalamo-pituitary-adrenal axis. These metabolic and hormonal influences are lead to change in brain neuromediator activity, such as reduced monamine and increased serotonin levels. Experimental data indicate that these neuromediator changes are responsible more for behavioral changes than for decreased physical performance.

Hormonal and metabolic adaptation in professional cyclists during training.

The aim of this study was to examine hormonal and metabolic changes in a group of 18 professional male cyclists ((.)VO(2)max 69.9 [95 % CI 64.9 to 74.9] mL x kg(-1) x min(-1) ) during two successive periods of adapted intensive training. The second training period included 4 days of cycling competition. Intensity was increased while volume was decreased in the second training. Anthropometric data were collected before and at the end of the two training periods. Venous blood samples were taken in a basal state before the two training sessions and after each training session. Serum concentrations of cortisol (C), testosterone (T), dehydroepiandrosterone sulfate (DHEAs), and catecholamines were determined as well as branched-chain amino acids (valine, leucine, isoleucine) (BCAA) and free fatty acids (FFAs). At the end of the two training periods, the subjects lost fat mass whereas mean body mass was unchanged. The T/C ratio was reduced transiently after the first training session (45.90 %), while DHEAs/C remained unchanged. T/C and DHEAs/C were significantly increased after the second training session compared to the first (48.40 and 97.18 %, respectively). Catecholamines and FFAs were unchanged. The significant increase in BCAA levels after the second training session was of note as it might constitute a "store shape" of amino acids in anticipation of future intense training loads. Based on the responses of testosterone, DHEAs, and cortisol, and on the training-induced increase in BCAA, there appeared to be hormonal and metabolic adaptation despite the inherent psychological stress of competition.

Regulation of proteolysis during reloading of the unweighted soleus muscle.

There is little information on the mechanisms responsible for muscle recovery following a catabolic condition. To address this point, we reloaded unweighted animals and investigated protein turnover during recovery from this highly catabolic state and the role of proteolysis in the reorganization of the soleus muscle. During early recovery (18 h of reloading) both muscle protein synthesis and breakdown were elevated (+65%, P<0.001 and +22%, P<0.05, respectively). However, only the activation of non-lysosomal and Ca(2+)-independent proteolysis was responsible for increased protein breakdown. Accordingly, mRNA levels for ubiquitin and 20S proteasome subunits C8 and C9 were markedly elevated (from +89 to +325%, P<0.03) and actively transcribed as shown by the analysis of polyribosomal profiles. In contrast, both cathepsin D and 14-kDa-ubiquitin conjugating enzyme E2 mRNA levels decreased, suggesting that the expression of such genes is an early marker of reversed muscle wasting. Following 7 days of reloading, protein synthesis was still elevated and there was no detectable change in protein breakdown rates. Accordingly, mRNA levels for all the proteolytic components tested were back to control values even though an accumulation of high molecular weight ubiquitin conjugates was still detectable. This suggests that soleus muscle remodeling was still going on. Taken together, our observations suggest that enhanced protein synthesis and breakdown are both necessary to recover from muscle atrophy and result in catch-up growth. The observed non-coordinate regulation of proteolytic systems is presumably required to target specific classes of substrates (atrophy-specific protein isoforms, damaged proteins) for replacement and/or elimination.

Immune and hormonal changes following intense military training.

This study was designed to determine whether the immune and hormonal systems were affected by a 5-day military course following 3 weeks of combat training in a population of 26 male soldiers (mean age, 21 +/- 2 years). The combination of continuous heavy physical activity and sleep deprivation led to energy deficiency. At the beginning of the training program and immediately after the combat course, saliva samples were assayed for secretory immunoglobulin A and plasma samples were assayed for interleukin-6, dehydroepiandrosterone sulfate, prolactin, catecholamines, glucocorticoids, and testosterone. Secretory immunoglobulin A was lower and circulating interleukin-6 was increased by the end of the course, which was attributed to sympathoadrenergic stimulation. Dehydroepiandrosterone sulfate, prolactin, and testosterone levels fell significantly. These results suggest that prolonged and repeated exercise such as that encountered in a military training program induces immune impairment via a decrease in mucosal immunity and a release of interleukin-6 into the circulation. The impaired secretion of dehydroepiandrosterone sulfate and prolactin, two immunomodulatory hormones, was thought to be a response to the chronic stressors. Lowered testosterone reflects a general decrease in steroid synthesis as a consequence of the physical and psychological strain.

Decrease in serum leptin after prolonged physical activity in men.

PURPOSE: This study was designed to determine whether serum leptin levels were affected by a 5-d military course after 3 wk of combat training. METHODS: 26 male soldiers (mean age = 21 +/- 2 yr) were examined at the beginning of the training program and just at the end of the 5-d course. The combination of continuous heavy physical activity and sleep deprivation led to energy deficiency. Blood samples were analyzed for serum leptin, insulin, cortisol, adrenocorticotropin (ACTH), and testosterone; plasma was analyzed for free fatty acids (FFA), glycerol, glucose, and catecholamines. RESULTS: At the end of the 5-d course, there was a significant reduction in serum leptin (0.40 +/- 0.04 ng x mL(-1) versus 1.47 +/- 0.14 ng x mL(-1), < 0.001), i.e., a mean decrease of 67.00 +/- 3.75%. Plasma norepinephrine and dopamine rose significantly from 296 +/- 17 ng x L(-1) to 672 +/- 48 ng x L(-1) and 23 +/- 3 ng x L(-1) to 40 +/- 5 ng x L(-1) ( < 0.001 and < 0.01, respectively), whereas epinephrine remained unchanged. Serum concentrations of the anabolic hormone, insulin, fell from 31.17 +/- 3.03 microU x mL(-1) to 17.79 +/- 1.58 microU x mL(-1) ( < 0.001), whereas plasma FFA and glycerol were increased ( < 0.001, < 0.05, respectively). A statistically significant correlation appeared between the changes in leptin and insulin (r = 0.5306, < 0.01). Serum testosterone decreased significantly ( < 0.001), whereas serum cortisol, ACTH, and plasma glucose were unchanged at the end of the course. The training program had no significant effect on mean body mass index. CONCLUSION: A 4-wk strenuous military training program, which induced an energy deficiency, reduced serum leptin to a third of normal levels. The decrease in serum leptin was attributed to the exercise-induced elevation in catecholamines and hypoinsulinemia.