Effect of sprint cycling and stretch-shortening cycle exercises on the neuromuscular, immune and stress indicators in young men.

Selection of optimal physical load is essential for desired adaptation including health benefits. We hypothesized that neuromuscular, immune and stress indicators will be higher after energy demanding sprint interval exercise (SIE) than to mechanically demanding stretch-shortening cycle exercise (SSE). The main aim of this study was to assess and compare the kinetics of blood brain-derived neurotrophic factor (BDNF), norepinephrine (NE) and cortisol (as stress indicators) and proinflammatory (IL-6) and anti-inflammatory (IL-10) cytokines within 24 hours after metabolically demanding SIE and after muscle damage inducing SSE. Twenty healthy physically active young men randomly assigned to two equal groups to complete 12 bouts of 5 s stationary cycling sprints every 3 min (SIE) or 200 drop-jumps with 30 s interval between each jump (SSE), respectively. Quadriceps muscle maximal voluntary contraction torque and voluntary activation and soreness were measured and blood samples collected before and 2 min, 1 hour, 12 hours and 24 hours after the SIE and SSE. The BDNF, cortisol, IL-6 and NE levels increased more at 2 min after SIE than SSE (P < 0.05); however, the IL-10 level did not differ between SIE and SSE. BDNF and cortisol levels were decreased at 24 h after both SIE and especially after SSE. The higher was the initial BDNF level, the greater was its decrease at 24 h after both type of exercise. Before exercise BDNF level correlated closely with the change in central fatigue (decrease in voluntary activation) after both SIE and SSE. We thus conclude that both metabolically demanding SIE and muscle damage inflicting SSE induced long-lasting decrease in circulating BDNF which may not promote brain health. The level of circulating BDNF, but not cortisol, IL-6, IL-10 or NE, was associated with changes in central motor fatigue.

[Fibromyalgia syndrome: A disease of the small nerve fibers?]. / Fibromyalgiesyndrom : Eine Erkrankung der kleinen Nervenfasern?

Fibromyalgia syndrome (FMS) is characterized by chronic widespread pain and additional associated symptoms, such as fatigue, sleep disturbances and depressive moods. The pathophysiology of pain in FMS is unclear. In recent years, an involvement of the thinly myelinated A-delta and the unmyelinated C-nerve fibers has been reported in FMS patients. Independent research groups published consistent objective and multidimensional findings of damage to these small nerve fibers, such as disturbances of fiber function, electrical properties and morphological changes. All these alterations are not specific for FMS; however, they were described for the first time in subgroups of FMS patients. While the reasons for this small fiber pathology and its contribution to FMS pain are still unclear, a new research field has now been opened that will focus on uncovering the underlying pathophysiology. This review article summarizes these new findings and discusses the significance for the understanding of FMS.

Neuromyelitis optica preceded by hyperCKemia episode.

BACKGROUND: Neuromyelitis optica (NMO) is a disease of the CNS characterized by severe optic neuritis and longitudinally extended transverse myelitis. Recent studies suggest that anti-aquaporin-4 (AQP4) antibodies, NMO-specific biomarkers, are pathogenic and target AQP4-expressing astrocytes in NMO, although an additional event (T-cell response or infection) should occur for anti-AQP4 antibodies and complements to pass through the blood-brain barrier and cause the CNS lesions. AQP4 is the major water channel in the CNS, but it is also expressed in fast-twitch skeletal muscle fibers. However, muscle diseases have not been described in NMO. METHODS: We retrospectively examined the serologic database of 733 cases of NMO with anti-AQP4 antibody at the Department of Neurology, Tohoku University School of Medicine. The serum samples were sent to our laboratory for testing anti-AQP4 antibody from around the country during the period from 2006 to 2009. RESULTS: We found 3 anti-AQP4 antibody-positive female patients (7, 34, and 67 years old) with NMO who had episodes of prominent hyperCKemia (12,520, 19,415, and 59,660 IU/L) with general fatigue some weeks before the onset of optic neuritis. HyperCKemia was transient without any treatment in all patients, but recurred once in one of them. CONCLUSIONS: These cases suggest that hyperCKemia may be involved in the pathogenesis of neuromyelitis optica (NMO) in a fraction of patients. The causes of transient hyperCKemia are unknown. Further studies are needed to know the frequency of hyperCKemia in NMO and clarify its pathogenic role.

Salivary secretory immunoglobulin a response of elite speed skaters during a competition period.

We aimed to determine the responses of salivary secretory immunoglobulin A (SIgA) and the incidence of upper respiratory tract infections (URTI) symptoms among elite speed skaters during an actual competition period. The subjects were 8 international-class elite speed skaters. Saliva samples were obtained 3, 2, and 1 days before the race, the day of the race, and 1 day after the race. Salivary secretory immunoglobulin A concentration was measured by enzyme immunoassay, and SIgA secretion rate was calculated. A visual analogue scale was used to subjectively assess fatigue and tension. Daily URTI symptoms were recorded by using a questionnaire. There was no statistically significant difference in the saliva flow rate (p = 0.69), SIgA concentration (p = 0.07), and subjective fatigue (p = 0.07) during the competition period. The SIgA secretion rate recorded for the day of the race was significantly high compared with that of 3 and 2 days before and 1 day after the race (p < 0.05). The subjective tension recorded on the race day was significantly high compared with that for 3, 2, and 1 days before the race (p < 0.05). Two subjects exhibited URTI symptoms after the race. These findings suggest that salivary SIgA in elite speed skaters increased after a tapering period and that an actual high-intensity speed skating race decreased salivary SIgA in elite speed skaters. These data also suggest that the incidence of URTI symptoms might be related to the SIgA level. Coaches may need to take precautions after competitions to minimize their athletes' contact with cold viruses and adjust training load for a few days after competition to improve the decreased mucosal immune function.

Salivary IgA as a risk factor for upper respiratory infections in elite professional athletes.

UNLABELLED: The relationship between physiological and psychological stress and immune function is widely recognized; however, there is little evidence to confirm a direct link between depressed immune function and incidence of illness in athletes. PURPOSE: To examine the relationship between salivary immunoglobulin A (s-IgA) and upper respiratory infections (URI) in a cohort of professional athletes over a prolonged period. METHODS: Thirty-eight elite America's Cup yacht racing athletes were studied over 50 wk of training. Resting, unstimulated saliva samples were collected weekly (38 h after exercise, consistent time of day, fasted) together with clinically confirmed URI, training load, and perceived fatigue rating. RESULTS: s-IgA was highly variable within (coefficients of variation [CV] = 48%) and between subjects (CV = 71%). No significant correlation was found between absolute s-IgA concentration and the incidence of URI among athletes (r = 0.11). However, a significant (28%, P < 0.005) reduction in s-IgA occurred during the 3 wk before URI episodes and returned to baseline by 2 wk after a URI. When an athlete did not have, or was not recovering from URI, a s-IgA value lower than 40% of their mean healthy s-IgA concentration indicated a one in two chance of contracting an URI within 3 wk. CONCLUSION: On a group basis, relative s-IgA determined a substantial proportion of the variability in weekly URI incidence. The typical decline in an individual's relative s-IgA over the 3 wk before a URI appears to precede and contribute to URI risk, with the magnitude of the decrease related to the risk of URI, independent of the absolute s-IgA concentration. These findings have important implications for athletes and coaches in identifying periods of high URI risk.

High-intensity exercise elicits the mobilization of senescent T lymphocytes into the peripheral blood compartment in human subjects.

Clonal expansion of T lymphocytes in response to antigenic stimulation is a fundamental process of adaptive immunity. As a consequence of clonal expansion, some T lymphocytes acquire a senescent phenotype, fail to replicate in response to further antigenic stimulation, and express the killer cell lectin-like receptor G1 (KLRG1) and/or CD57. Physical exercise elicits a mobilization of large numbers of T lymphocytes into the bloodstream from peripheral lymphoid compartments, but the frequency of senescent cells in the mobilized population is not known. Eight male runners (age: 29 +/- 9 yr; maximal O2 uptake 62 +/- 6 ml x kg(-1) x min(-1)) performed an intensive treadmill-running protocol at 80% maximal O2 uptake to volitional exhaustion. Blood lymphocytes isolated before, immediately after, and 1 h after exercise were assessed for cell surface expression of KLRG1, CD57, CD28, CD45RA, CD45RO, CD62L, and lymphocyte subset markers (CD3, CD4, CD8, CD56) by flow cytometry. The percentage of all CD3+ T lymphocytes expressing KLRG1 and CD57 increased with exercise (P < 0.01). The change in T-lymphocyte KLRG1 expression was attributed to both CD4+ and CD8 bright T cells, with the relative change being greater for the CD8 bright population (P < 0.01). Mobilized T-lymphocyte populations expressing KLRG1 and CD57 appeared to extravasate the peripheral blood compartment after 1 h of recovery. In conclusion, T lymphocytes with a senescent phenotype are mobilized and subsequently removed from the bloodstream in response to acute high-intensity exercise. This suggests that T lymphocytes contained within the peripheral lymphoid compartments that are mobilized by exercise are likely to be at a more advanced stage of biological aging and have a reduced capacity for clonal expansion than blood-resident T cells.

Is chronic fatigue syndrome an autoimmune disorder of endogenous neuropeptides, exogenous infection and molecular mimicry?

Chronic fatigue syndrome is a disorder characterised by prolonged fatigue and debility and is mostly associated with post-infection sequelae although ongoing infection is unproven. Immunological aberration is likely and this may prove to be associated with an expanding group of vasoactive neuropeptides in the context of molecular mimicry and inappropriate immunological memory. Vasoactive neuropeptides including vasoactive intestinal peptide (VIP) and pituitary adenylate activating polypeptide (PACAP) belong to the secretin/glucagon superfamily and act as hormones, neurotransmitters, immune modulators and neurotrophes. They are readily catalysed to smaller peptide fragments by antibody hydrolysis. They and their binding sites are immunogenic and are known to be associated with a range of autoimmune conditions. Vasoactive neuropeptides are widely distributed in the body particularly in the central, autonomic and peripheral nervous systems and have been identified in the gut, adrenal gland, reproductive organs, vasculature, blood cells and other tissues. They have a vital role in maintaining vascular flow in organs, and in thermoregulation, memory and concentration. They are co-transmitters for acetylcholine, nitric oxide, endogenous opioids and insulin, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system to toxic assault, promotion of neural development and the maintenance of homeostasis. This paper describes a biologically plausible mechanism for the development of CFS based on loss of immunological tolerance to the vasoactive neuropeptides following infection, significant physical exercise or de novo. It is proposed that release of these substances is accompanied by a loss of tolerance either to them or their receptor binding sites in CFS. Such an occurrence would have predictably serious consequences resulting from compromised function of the key roles these substances perform. All documented symptoms of CFS are explained by vasoactive neuropeptide compromise, namely fatigue and nervous system dysfunction through impaired acetylcholine activity, myalgia through nitric oxide and endogenous opioid dysfunction, chemical sensitivity through peroxynitrite and adenosine dysfunction, and immunological disturbance through changes in immune modulation. Perverse immunological memory established against these substances or their receptors may be the reason for the protracted nature of this condition. The novel status of these substances together with their extremely small concentrations in blood and tissues means that clinical research into them is still in its infancy. A biologically plausible theory of CFS causation associated with vasoactive neuropeptide dysfunction would promote a coherent and systematic approach to research into this and other possibly associated disabling conditions.

Chronic fatigue syndrome: intracellular immune deregulations as a possible etiology for abnormal exercise response.

The exacerbation of symptoms after exercise differentiates Chronic fatigue syndrome (CFS) from several other fatigue-associated disorders. Research data point to an abnormal response to exercise in patients with CFS compared to healthy sedentary controls, and to an increasing amount of evidence pointing to severe intracellular immune deregulations in CFS patients. This manuscript explores the hypothetical interactions between these two separately reported observations. First, it is explained that the deregulation of the 2-5A synthetase/RNase L pathway may be related to a channelopathy, capable of initiating both intracellular hypomagnesaemia in skeletal muscles and transient hypoglycemia. This might explain muscle weakness and the reduction of maximal oxygen uptake, as typically seen in CFS patients. Second, the activation of the protein kinase R enzyme, a characteristic feature in atleast subsets of CFS patients, might account for the observed excessive nitric oxide (NO) production in patients with CFS. Elevated NO is known to induce vasidilation, which may limit CFS patients to increase blood flow during exercise, and may even cause and enhanced postexercise hypotension. Finally, it is explored how several types of infections, frequently identified in CFS patients, fit into these hypothetical pathophysiological interactions.

Immunological responses to overreaching in cyclists.

INTRODUCTION: Acute bouts of prolonged strenuous exercise are often associated with immune suppression and an increased risk of infection. However, few studies have examined immunological responses to intensified training that results in overreaching or overtraining. We investigated the effects of intensified training on plasma cytokines, glutamine, glutamate, and other related immunological variables in endurance-trained cyclists. METHODS: Eight male subjects (age 27.0 +/- 3.0 yr, [OV0312]O(2max) 58.0 +/- 1.7 mL.kg-1.min-1, mass 73.7 +/- 2.1 kg) completed 6 wk of training: 2 wk each of normal training (N, 7 +/- 2 h.wk-1), intensified training (ITP, 14 +/- 5 h.wk-1) and recovery training (R, 3.5 +/- 2.5 h.wk-1). During the study period, subjects completed six graded cycle ergometer tests to exhaustion (MT), six simulated time trial tests (TT), and eight 2 x 10-min maximal effort bouts (IT). Subjects also completed questionnaires to assess mood state. Plasma concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), salivary IgA, plasma glutamine, glutamate, ammonia, urea, creatine kinase activity, and routine hematological measures were determined once per week. RESULTS: ITP resulted in overreaching in all subjects identified by a significant decline in performance and disturbances of mood state. Significant increases during the ITP were observed in creatine kinase activity and glutamate, whereas the glutamine/glutamate ratio (Gln/Glu ratio), red blood cell numbers (RBC), hemoglobin concentration (Hb), and packed cell volume (PCV) declined after ITP. No significant changes were observed in TNF-alpha, IL-6, salivary IgA, glutamine, ammonia, urea and various routine hematological measures. CONCLUSION: Alterations in plasma cytokines do not appear to be related to the decline in performance and increased mood state characteristic of overreaching; however, the Gln/Glu ratio may be of use as a marker of overreaching and/or overtraining.

[Effects of physical exhaustion on immune systems].

The present study was performed to elucidate the effects of physical fatigue on immune parameters of peripheral blood and splenic T cells in rats. Male Wistar rats aged 20 to 45 weeks were used for the experiment. Swimming was employed as a physical fatigue load. The rats in the single-load group with a weight equal to 3% of the body weight of each rat connected to the tails were exhausted by two hours of swimming in one day. The rats in the consecutive-load group were exhausted by three hours of swimming for 7 consecutive days with a weight equal to 5% of the body weight of each rat. Absolute numbers of total white blood cells (WBCs) and peripheral blood lymphocytes decreased significantly just after swimming and returned to the baseline one day after swimming in both the single- and consecutive-load groups. However, in the consecutive-load group WBCs and lymphocytes decreased 7 days after swimming. Concentrations of plasma corticosterone increased significantly just after swimming, and returned to the baseline one day after swimming in both groups. Percentages of peripheral blood CD5+ cells, CD4+ cells and CD8+ cells in the single-load group increased significantly just after swimming. The percentage of peripheral blood CD5+ cells and CD4+ cells increased significantly one day after swimming in the consecutive load group. Percentages of splenic CD5+ cells and CD4+ cells increased significantly in the single-load group. However, only that of CD4+ cells increased significantly just after swimming in the consecutive-load group. A single load affected the proportions of CD5+ cells, CD4+ cells and CD8+ cells just after the load but the consecutive load affected CD5+ cells and CD4+ cells and the effect persisted until the next day. These results indicate that the effect of fatigue on immune parameters depends on the level of fatigue, and that measurement of subsets of peripheral blood T cells is useful for evaluating various levels of fatigue.

Load dependence of secondary diaphragm inflammation and injury after acute inspiratory loading.

Chronic or prolonged low-intensity loading of the inspiratory muscles has recently been shown to produce diaphragm injury. The present study was designed to examine whether an acute episode of inspiratory resistive loading (IRL) could produce secondary diaphragm inflammation and injury. On Day 1, three groups of anesthetized and intubated New Zealand White rabbits were subjected to moderate IRL (Pao of approximately 30 cm H2O), high IRL (Pao of approximately 45 cm H2O), or no load for 1.5 h. On Day 3, costal and crural diaphragms, parasternals, and gastrocnemius muscles were taken to assess injury by point counting. Normal muscle, abnormal and inflamed muscle, and connective tissue on hematoxylin and eosin-stained cross-sections were expressed as percentage of the total points for that cross-section. For the costal diaphragm, both the abnormal muscle (7.3 +/- 0.6% versus 1.1 +/- 0.2%; p < 0.001) and connective tissue (8.0 +/- 0.6% versus 5.7 +/- 0.2%; p < 0.01) in the high IRL group were higher than control, whereas in the moderate IRL group they were not significantly different from control. Total calpain-like activity was increased in the moderate IRL group but not in the high IRL group. Injury was observed in the parasternal muscles but to a lesser extent. No injury was observed in the gastrocnemius muscle. We conclude that secondary diaphragm injury occurs after acute IRL but only when the IRL exceeds the fatigue threshold.