Revised contraindications for the use of non-medical WB-electromyostimulation. Evidence-based German consensus recommendations.

Whole-body electromyostimulation has proven to be a highly effective alternative to conventional resistance-type exercise training. However, due to adverse effects in the past, very extensive contraindications have been put in place for the commercial, non-medical WB-EMS market. Considering recent positive innovations e.g., federal regulation, mandatory trainer education, revised guidelines, and new scientific studies on WB-EMS application, we believe that a careful revision of the very restrictive contraindications on WB-EMS is needed. This applies all the more because many cohorts with limited options for conventional exercise have so far been excluded. During a first meeting of an evidence-based consensus process, stakeholders from various backgrounds (e.g., research, education, application) set the priorities for revising the contraindications. We decided to focus on four categories of absolute contraindications: "Arteriosclerosis, arterial circulation disorders", "Diabetes mellitus" (DM), "Tumor and cancer" (TC), "Neurologic diseases, neuronal disorders, epilepsy". Based on scientific studies, quality criteria, safety aspects and benefit/risk assessment of the category, DM and TC were moved to the relative contraindication catalogue, while arteriosclerosis/arterial circulation disorders and neurologic diseases/neuronal disorders/epilepsy were still considered as absolute contraindications. While missing evidence suggests maintaining the status of neurologic diseases/neuronal disorders as an absolute contraindication, the risk/benefit-ratio does not support the application of WB-EMS in people with arteriosclerosis/arterial circulation diseases. Despite these very cautious modifications, countries with less restrictive structures for non-medical WB-EMS should consider our approach critically before implementing the present revisions. Considering further the largely increased amount of WB-EMS trials we advice regular updates of the present contraindication list.

Effects of Escherichia coli strain Nissle 1917 on exercise-induced disruption of gastrointestinal integrity.

PURPOSE: The aim of the current study was to investigate the effects of the probiotic Escherichia coli strain Nissle 1917 (EcN) on the exercise-induced disruption of gastrointestinal (GI) integrity and the associated release of damage and inflammatory markers. METHODS: After a pre-performance test, 19 untrained subjects (aged 18-35 years) passed two identical exhaustive treadmill exercise tests in an intensity corresponding to 60-80% VO2max in a test-retest design. The exercise tests were separated by a time period of 4 weeks. During this period, all subjects ingested 5 ml of an EcN suspension daily. Serum samples were taken before, immediately following and 3 h after both exercise tests. They were analyzed for indicators of GI integrity (zonulin; claudin-3; LPS), various damage and redox markers (I-FABP, GOT; GPT; TBARS) and inflammatory parameters (hsCRP; leucocytes). GI complaints were evaluated by a questionnaire. RESULTS: The intake of EcN resulted in a significantly lower increase in I-FABP and TBARS after exercise (p < 0.05). In contrast, no effect of EcN supplementation was found for hsCRP and leucocyte numbers. Similarly, no differences were found for levels of zonulin and claudin-3. Exercise-associated GI complaints were not affected by the probiotic supplement. CONCLUSION: The probiotic EcN reduced the exercise-associated increase in oxidative stress. This antioxidative mechanism probably leads to a reduction of GI epithelial damage after exhaustive exercise. The lack of EcN effects on other markers of GI permeability and systemic inflammation is most likely due to an inadequate exercise load, with rather small and insignificant exercise effects on these parameters.

Exercise-induced cytokine changes in antigen stimulated whole-blood cultures compared to serum.

Strenuous exercise is followed by an elevation of many cytokines with inflammation regulating properties. Since most cytokines act at pico- or nanomolar concentrations many investigations failed to detect their concentrations in vivo. Hence, the aim of this study was to evaluate the significance of cytokine measurements (IL-1ß, TNF-α, IL-1ra, IL-6, CCL2 and CXCL8) in a stimulated whole-blood culture (sWBC) compared to serum with respect to their exercise-induced kinetics and detection rates. 40 male volunteers (age: 25,5±4,3years, BMI: 24,00±2,24, VO2peak: 46,9±4,1mL/kg×min) performed 60min of intensive bicycle exercise (80% VO2peak). Blood samples were taken before and for up to 24h after exercise. All cytokines were determined by a multiplex ELISA. There were weak to moderate correlations between cytokines in sWBC and serum. While exercise did not affect pro-inflammatory cytokines in serum, in sWBC only IL-1ß was increased 1.2-fold at 3h (p<0,05). All other cytokines increased both in sWBC and serum. The detection rate was superior in sWBC vs serum for most cytokines. Exercise-induced cytokine kinetics in sWBC do not reflect systemic changes. Both approaches provide a synergistic insight into inflammatory processes on the cytokine level.

Different effects of strength and endurance exercise training on COX-2 and mPGES expression in mouse brain are independent of peripheral inflammation.

Acute endurance exercise has been shown to modulate cyclooxygenase (COX)-2 expression, which is suggested to affect neuronal plasticity and learning. Here, we investigated the effect of regular strength and endurance training on cerebral COX-2 expression, inflammatory markers in the brain, and circulating cytokines. Male C57BL/6N mice were assigned to either a sedentary control group (CG), an endurance training group (EG; treadmill running for 30 min/day, 5 times/wk, 10 wk), or a strength training group (SG; strength training by isometric holding, same duration as EG). Four days after the last bout of exercise, blood and brain were collected and analyzed using real-time PCR, Western blot, and a multiplexed immunoassay. In EG, COX-2 mRNA expression in the cortex/hippocampus increased compared with CG. A significant increase of COX-2 protein levels was observed in both cortex/hippocampus and hypothalamus of mice from the SG. Nuclear factor (NF)κB protein levels were significantly increased in mice from both exercise groups (hypothalamus). A significant increase in the expression of microsomal prostaglandin E synthase (mPGES), an enzyme downstream of COX-2, was found in the hypothalamus of both the EG and SG. While most inflammatory factors, like IL-1α, IL-18, and IL-2, decreased after training, a positive association was found between COX-2 mRNA expression (cortex/hippocampus) and plasma IL-6 in the EG. Taken together, this study demonstrates that both endurance as well as strength training induces COX-2 expression in the cortex/hippocampus and hypothalamus of mice. A potential mediator of COX-2 expression after training might be circulating interleukin (IL)-6. However, further research is necessary to elucidate the role of inflammatory pathways on brain plasticity after training.

Time course of cigarette smoke-induced changes of systemic inflammation and muscle structure.

It has become more evident that long-term cigarette smoking (LTCS) has an important extrapulmonary toxicity. The aim of the study was to investigate the time-dependent effects of cigarette smoke exposure on exercise capacity, markers of systemic inflammation, and skeletal muscle structure. c57bl/6j-mice were either exposed to mainstream cigarette smoke for 6 h/day, 5 days/wk [smoke-exposed (SE) group] or assigned to the control, unexposed group (Con group). SE group mice were exposed for 8, 16, 24, and 32 wk to smoke and unexposed Con mice were used as age-matched controls. Exercise capacity was investigated by spiroergometry. Systemic inflammatory status was analyzed by flow cytometry and multiplexed fluorescent immunoassay. For analysis of muscle tissue, histological techniques and microarray analysis were used. Mice of the SE group exhibited a lower increase of body mass and a decrease of V̇o2 max (P < 0.05). An increase of lymphocyte CD62, ICAM, and VCAM expression was found in SE mice (P < 0.05). A biphasic trend of protein up- and downregulation was observed in markers of systemic inflammation, tissue deterioration, and allergic reactions such as C-reactive protein (CRP), eotaxin, haptoglobin, macrophage colony-stimulating factor-1 (M-CSF-1), and macrophage inflammatory protein-1γ (MIP-1γ). Thereby, the expression of several chemotactic proteins in plasma correlated with their expression in muscle. A time-dependent decrease of muscle mass, oxidative type-I fibers, and muscle cross-sectional area was found (P < 0.05). Microarray analysis revealed a SE-induced upregulation of several pathways of metabolic processes and tissue degradation. Taken together it was found that the loss of exercise capacity and systemic inflammation are early events of SE, which might induce muscular atrophy and loss of oxidative muscle capacity.

Exposure to total and protein-unbound rifampin is not affected by malnutrition in Indonesian tuberculosis patients.

Nutritional status may have a profound impact on the pharmacokinetics of drugs, yet only few data are available for tuberculosis (TB) drugs. As malnutrition occurs frequently among TB patients, we assessed the effect of malnutrition on the steady-state pharmacokinetics of total and protein-unbound rifampin during the intensive phase of TB treatment. In a descriptive pharmacokinetic study in Bandung, Indonesia, patients received a fixed standard rifampin dose of 450 mg once daily during the intensive phase of TB treatment. A full pharmacokinetic curve for rifampin was recorded, and total and unbound concentrations of rifampin were analyzed in all samples. Rifampin pharmacokinetic parameters were compared between severely malnourished (BMI of <16.0 kg/m(2)), malnourished (BMI of <18.5 kg/m(2)), and well-nourished (BMI of ≥18.5 kg/m(2)) individuals. No difference in total and protein-unbound pharmacokinetic parameters between severely malnourished (n = 7), malnourished (n = 11), and well-nourished (n = 25) patients could be demonstrated. In addition, no significant correlation between BMI and exposure (area under the concentration-time curve from 0 to 24 h [AUC0-24] and maximum concentration of drug in serum [Cmax]) was found. Females had significantly higher total AUC0-24 (geometric mean, 59.2 versus 48.2 h · mg/liter; P = 0.02) and higher unbound AUC0-24 (geometric mean, 6.2 versus 4.8 h · mg/liter; P = 0.02) than males. Overall, a marked 2-fold interindividual variation in the free fraction was observed (7.6 to 15.0%; n = 36). Nutritional status and BMI do not appear to have a major effect on total and protein-unbound pharmacokinetic parameters of rifampin in Indonesian subjects. The large interindividual variability in the free fraction of rifampin suggests that protein-unbound rather than total rifampin concentrations should preferably be used to study exposure-response relationships.

Progenitor cell mobilization after exercise is related to systemic levels of G-CSF and muscle damage.

Different types of exercise are characterized by the ability to induce specific physiological stimuli that might be able to induce the mobilization of progenitor cells. The aim of the current study was to investigate the mobilization of hematopoietic progenitor cells (HPCs) and endothelial progenitor cells (EPCs) in response to endurance, resistance, and eccentric endurance exercise and their relation to markers of muscle damage and inflammation. Healthy male subjects performed acute bouts of either endurance exercise, resistance exercise, or eccentric endurance exercise. Numbers of progenitor cells and several markers of muscle damage and inflammation were determined. Although the endurance exercise was followed by an immediate and short increase of both HPCs and EPCs, the eccentric exercise evoked a long lasting increase up to 24 h for HPCs and 48 h for EPCs (P < 0.05). After resistance exercise, an increase of HPCs was only found 3 h after exercise (P < 0.05). A correlation was found between mobilized progenitor cells and systemic levels of granulocyte colony-stimulating factor (G-CSF) levels (r = 0.54 and r = 0.51, P < 0.05) as well as for HPCs and creatine kinase levels (r = 0.57, P < 0.05). These results suggest that mobilization of progenitor cells is related to the type of exercise and possibly mediated by G-CSF and muscle damage.

Exploring effects of a natural combination medicine on exercise-induced inflammatory immune response: A double-blind RCT.

Traumeel (Tr14) is a natural, combination drug, which has been shown to modulate inflammation at the cytokine level. This study aimed to investigate potential effects of Tr14 on the exercise-induced immune response. In a double-blind, randomized, controlled trial, healthy, untrained male subjects received either Tr14 (n = 40) or placebo (n = 40) for 24 h after a strenuous experimental exercise trial on a bicycle (60 min at 80%VO2 max). A range of antigen-stimulated cytokines (in vitro), white blood cell count, lymphocyte activation and apoptosis markers, and indicators of muscle damage were assessed up to 24 h following exercise. The area under the curve with respect to the increase (AUCI ) was compared between both groups. The Tr14 group showed a reduced exercise-induced leukocytosis and neutrocytosis (P < 0.01 for both), a higher AUCI score of antigen-stimulated IL-1ß and IL-1α (absolute and per monocyte, all P < 0.05), a lower AUCI score of antigen-stimulated GM-CSF (P < 0.05) and by trend a lower AUCI score of antigen-stimulated IL-2 and IL-4 as well as a higher AUCI score of antigen-stimulated IL-6 (all P < 0.1). Tr14 might promote differentiated effects on the exercise-induced immune response by (a) decreasing the inflammatory response of the innate immune system; and (b) augmenting the pro-inflammatory cytokine response.

PTPIP51: a new interaction partner of the insulin receptor and PKA in adipose tissue.

AIMS: Our previous experiments revealed an association of PTPIP51 (protein tyrosine phosphatase interacting protein 51) with the insulin signalling pathway through PTP1B and 14-3-3beta. We aimed to clarify the role of PTPIP51 in adipocyte metabolism. METHODS: Four groups of ten C57Bl/6 mice each were used. Two groups were fed a standard diet; two groups were fed a high-fat diet. Two groups (one high-fat diet and one standard diet) were submitted to endurance training, while the remaining two groups served as untrained control groups. After ten weeks, we measured glucose tolerance of the mice. Adipose tissue samples were analyzed by immunofluorescence and Duolink proximity ligation assay to quantify interactions of PTPIP51 with either insulin receptor (IR) or PKA. RESULTS: PTPIP51 and the IR and PTPIP51 and PKA, respectively, were colocalized in all groups. Standard diet animals that were submitted to endurance training showed low PTPIP51-IR and PTPIP51-PKA interactions. The interaction levels of both the IR and PKA differed between the feeding and training groups. CONCLUSION: PTPIP51 might serve as a linking protein in adipocyte metabolism by connecting the IR-triggered lipogenesis with the PKA-dependent lipolysis. PTPIP51 interacts with both proteins, therefore being a potential gateway for the cooperation of both pathways.

Intensive resistance exercise induces lymphocyte apoptosis via cortisol and glucocorticoid receptor-dependent pathways.

Intensive endurance exercise is known to induce lymphocyte apoptosis, which might affect immune function. Less is known about the effects of resistance exercise on apoptosis and its underlying mechanisms. In this study, subjects performed an intensive resistance test (IRT) and a moderate resistance test, and lymphocyte apoptosis, apoptosis-related parameters, and underlying mechanisms were investigated. IRT induced a significant increase of lymphocyte apoptosis 3 h after exercise, which was accompanied by a significant decrease of mitochondrial membrane potential, a reduction of Bcl-2, and an upregulation of the CD95 receptor. Blood lactate, IL-6, C-reactive protein, and cortisol increased significantly 3 h after IRT. A significant correlation was observed between the increase of apoptosis and cortisol levels 3 h after IRT. Incubation of freshly isolated lymphocytes in IRT serum indicated an important role of serum correlates for apoptosis induction. Selective incubation of lymphocytes in concentrations of selected serum parameters corresponding to levels found post in IRT serum demonstrated a major role for cortisol in apoptosis induction. This result was confirmed by attenutation of apoptosis after addition of mifepristone before incubation in IRT serum. In summary, resistance exercise induced lymphocyte apoptosis in an intensity-dependent way. Furthermore, cortisol signaling via glucocorticoid receptors might be an important mechanism for lymphocyte apoptosis after resistance exercise.

PTPIP51 interaction with PTP1B and 14-3-3ß in adipose tissue of insulin-resistant mice.

OBJECTIVE: We investigated the expression of protein tyrosine phosphatase-interacting protein 51 (PTPIP51) and its interaction with protein tyrosine phosphatase 1B (PTP1B) and 14-3-3ß in mice exhibiting insulin resistance and obesity. DESIGN: A total of 20 mice were included in the study. Eight control animals were fed a normal standard diet, six animals were fed a high-fat diet and six animals were submitted to a treadmill training parallel to the feeding of a high-fat diet. After 10 weeks, a glucose tolerance test was performed and abdominal adipose tissue samples of the animals were collected. RESULTS: PTPIP51 protein was identified in the adipocytes of all samples. PTPIP51 interacted with PTP1B and with 14-3-3ß protein. Compared with untrained mice fed a standard diet, the interaction of PTPIP51 with PTP1B was reduced in high-fat diet-fed animals. The highest interaction of PTPIP51 with 14-3-3ß was seen in trained animals on high-fat diet, whereas untrained animals on high-fat diet displayed lowest values. CONCLUSION: PTPIP51 is expressed in adipose tissue of humans, rats and mice. Obesity with enhanced insulin resistance resulted in a reduction of PTPIP51 levels in adipocytes and influenced the interactions with PTP1B and 14-3-3ß. The interaction of PTPIP51 with PTP1B suggests a regulatory function of PTPIP51 in insulin receptor signal transduction. The interaction of PTPIP51 with 14-3-3ß, especially in trained individuals, hints to an involvement of PTPIP51 in the downstream regulation of insulin action.

Oral magnesium supplementation reduces insulin resistance in non-diabetic subjects - a double-blind, placebo-controlled, randomized trial.

The incidence of insulin resistance and metabolic syndrome correlates with the availability of magnesium (Mg). We studied the effect of oral Mg supplementation on insulin sensitivity and other characteristics of the metabolic syndrome in normomagnesemic, overweight, insulin resistant, non-diabetic subjects. Subjects were tested for eligibility using oral glucose tolerance test (OGTT) and subsequently randomized to receive either Mg-aspartate-hydrochloride (n = 27) or placebo (n = 25) for 6 months. As trial endpoints, several indices of insulin sensitivity, plasma glucose, serum insulin, blood pressure and lipid profile were determined. Mg supplementation resulted in a significant improvement of fasting plasma glucose and some insulin sensitivity indices (ISIs) compared to placebo. Blood pressure and lipid profile did not show significant changes. The results provide significant evidence that oral Mg supplementation improves insulin sensitivity even in normomagnesemic, overweight, non-diabetic subjects emphasizing the need for an early optimization of Mg status to prevent insulin resistance and subsequently type 2 diabetes.

Physical activity and memory functions: an interventional study.

Previous studies have suggested beneficial effects of physical activity on cognition. Here, we asked in an interventional approach if physical activity performed at different intensity levels would differentially affect episodic memory function. Additionally, we tried to identify mechanisms mediating these changes. Sixty-two healthy elderly individuals were assessed for level of physical activity, aerobic fitness, episodic memory score, neurotrophin and catecholamine levels, and received a magnetic resonance image of the brain at baseline and after a six months intervention of medium or low-intensity physical activity or control. Increase in total physical activity was positively associated with increase in memory score over the entire cohort, without significant differences between intensity groups. It was also positively associated with increases in local gray matter volume in prefrontal and cingulate cortex, and BDNF levels (trend). In conclusion, we showed that physical activity conveys the beneficial effects on memory function independently of its intensity, possibly mediated by local gray matter volume and neurotrophic factors. Our findings may carry significant implications for prevention of cognitive decline in the elderly.

Physical activity and memory functions: are neurotrophins and cerebral gray matter volume the missing link?

Epidemiological studies reveal better cognitive function in physically active individuals. Possible mediators for this effect are neurotrophins, which are up-regulated through physical exercise and induce neuronal growth and synaptogenesis in the animal model. Here we cross-sectionally assessed 75 healthy older individuals for levels of physical activity, aerobic fitness, and memory encoding, as well as neurotrophin levels and cerebral gray matter volume. We found that physical activity, but not cardiovascular fitness, was associated with better memory encoding after controlling for age, sex, education, depression, alcohol consumption, and smoking. Higher levels of physical activity were associated with higher levels of the neurotrophin granulocyte colony stimulating factor (G-CSF) and increased cerebral gray matter volume in prefrontal and cingulate cortex as assessed by magnetic resonance voxel-based morphometry. While mediating factors will need to be further elucidated, these findings indicate that even low-level physical activity exerts beneficial effects on memory functions in older individuals.

Exercise affects tissue lymphocyte apoptosis via redox-sensitive and Fas-dependent signaling pathways.

Intensive and exhaustive exercise induces an activation of blood T-lymphocytes, which seems to be terminated by apoptotic processes in the postexercise period. Here, we report that exercise-induced T-lymphocyte apoptosis is a systemic phenomenon occurring in various lymphoid and nonlymphoid tissues. The apoptosis rate could be related to exercise intensity and type. Although in some tissues, such as the spleen and Peyer's patches, an early start of apoptosis (1-3 h postexercise) could be detected, a delayed apoptosis (24 h postexercise) was observed in lung, bone marrow, and lymph nodes. Further analysis showed a similar apoptosis distribution among lymphocyte subpopulations. We tested whether components of the extrinsic or the intrinsic apoptotic pathways or both were involved in these processes. Elevated levels of lipid peroxidation-product malondialdehyde (MDA), indicating an increased production of reactive oxygen species (ROS), were found after exercise in Peyer's patches, lung, and spleen, but not in lymph nodes. Application of N-acetyl-cysteine (NAC) prevented exercise-induced T-cell apoptosis completely in spleen and bone marrow, partially in lung and Peyer's patches, while it was ineffective in lymph nodes. Additionally, exercise addressed the Fas-mediated apoptosis. The percentage of Fas-receptor (Fas+) and Fas-ligand positive (FasL+) lymphocytes was enhanced in Peyer's patches after exercise. Moreover, FasL+ T cells were increased in the lung, while in lymph nodes Fas+ cells were increased. The critical role of Fas signaling in exercise-induced apoptosis was supported by using Fas-deficient MRL/lpr-mice. In Fas-deficient mice, exercise-induced T-lymphocyte apoptosis was prevented in spleen, lung, bone marrow, and lymph nodes, but not in Peyer's patches. These data demonstrate that exercise-induced lymphocyte apoptosis is a transient systemic process with tissue-type specific apoptosis-inducing mechanisms, whose relevance for the adaptive immune competence remains to be shown.

Exercise-induced redistribution of T lymphocytes is regulated by adrenergic mechanisms.

Acute exercise is known for causing considerable changes in leukocyte counts and function. In this paper we report that differentiated changes in T-lymphocyte distribution occur in lymphoid and non-lymphoid organs depending on the type and the intensity of exercise. Using fluorescent cell tracking we observed a release of T-cells from the spleen while lung, bone marrow and Peyer's patches served as target organs. The number of T-cells in the blood rose after intensive running while lymphopenia occurred after swimming exercise. Changes in number of labelled T-cells were neither found in the lymph nodes nor in the thymus regardless of exercise protocol. Following an alpha- or beta-blockade, the exercise-induced release of T-cells from the spleen and the accumulation of T-cells in the lung were inhibited while the enhancement of T-cells in the Peyer's patches was not affected. The administration of epinephrine partially mimicked the effects of exercise and resulted in a release of T-cells from both, the spleen and the liver, as well as in an increase of circulating blood T-cells. In conclusion, exercise induces a substantial re-distribution of T-cells within lymphoid and non-lymphoid organs. The migrating properties of T-cells could be partially explained by adrenergic mechanisms associated with exercise while the involvement of certain homing receptors remains to be shown. Our results suggest that the accumulation of T-cells in both, lung and Peyer's patches, may enhance the immune vigilance in these compartments which serve as the body's major defence barriers.

PAR-2 activation regulates IL-8 and GRO-alpha synthesis by NF-kappaB, but not RANTES, IL-6, eotaxin or TARC expression in nasal epithelium.

BACKGROUND: The effects of protease-activated receptor-2 (PAR-2) stimulation on inflammation mechanisms of chronic rhinosinusitis (CRS) are still unknown. METHODS: PAR-2 receptor expression was investigated by immunohistochemistry and Taqman mRNA analysis in the mucosa of different rhinosinusitis entities. In primary nasal epithelial cell cultures, the function of PAR-2 and its ability to produce CXC, CC chemokines, and IL-6 were measured by calcium mobilization and stimulation tests. Inhibition tests were performed using cortisone, serine protease inhibitors, cysteine protease inhibitors, Pertussis toxin (PTX) and nuclear transcription factor (NF-kappaB) inhibition (BAY 11-7085). Signal transduction pathways were analysed by electromobility shift assays (EMSA) and NF-kappaB binding studies. RESULTS: The expression of PAR-2 was found to be increased in CRS specimens. The activation of PAR by trypsin or PAR-2-specific activating peptide (AP) caused an increase in cytosolic calcium, as well as the release of the CXC chemokines IL-8 and growth-related oncogene (GRO)-alpha, but not the release of CC chemokines or IL-6. AP-induced CXC chemokine was sensitive to PTX and activation of NF-kappaB was inhibited by BAY11-7085. Furthermore, a serine protease inhibitor significantly inhibited chemokine synthesis stimulated by trypsin and culture supernatants of staphylococci, whereas steroids and cysteine protease inhibitors had little effect. CONCLUSION: PAR-2 plays a role in serine protease-mediated regulation - staphylococcal and non-staphylococcal origin - of IL-8 and GRO-alpha in nasal epithelial cells, but not in the regulation of CC chemokines. PAR-2 may therefore be involved in the pathophysiology of CRS and NP at different sites of activation, namely (i) proteases, (ii) the PAR-2 receptor itself or (iii) the application of novel agents that block NF-kappaB/IkappaB-alpha signalling.

Participation in sports and physical activity of haemophilia patients.

Modern therapy options offer haemophiliacs more and more possibilities for an active participation in sports. The purpose of the present study was to investigate the attitude of these patients towards sports, their participation in school and leisure time sports activities, and differences between juveniles and adults. We investigated 44 children and adolescents (aged from 4 to 16 years) and 27 adults (aged from 18 to 72 years) with haemophilia by means of a questionnaire. 79.6% of the juvenile patients participated always or almost always in school sports, while this percentage was significantly (P < 0.05) lower in the former school time of the adults (37%). Sports play an important or very important role in leisure time activities for 75% of the adolescent and 55.5% of the adult haemophiliacs (P < 0.05). Bleeding complications occurred in 17.6% of all patients; there was no correlation with any particular type of sports. There were only slight differences between both groups, regarding their motivation to participate in sports activities. The main reasons involved social aspects and having fun. The results show that the modern therapy of haemophilia probably leads to a more positive attitude towards sports and to a wider spectrum of practised sports. This, however, may be associated with an increasing potential of health risks, which require a high level of sports medical care.

T cell homing and exercise.

Lymphocytes recirculate between the blood and lymph moving by routes that take them through various lymphoid and non-lymphoid organs in order to search for their cognate antigen. Naïve and effector/memory T cells provide distinct repertoires of receptors and ligands that constitute their ability to interact with the microvessels of different anatomical compartments and, consequently, have distinct patterns of migration. Lymphocyte migration from vascular to extravascular sites is a tightly controlled cascade of events, initiated by tethering and rolling interactions of lymphocytes on the endothelial surface. Local chemokines initiate in the activation of integrin adhesiveness, followed by firm arrest and endothelial transmigration. Environmental stress induces a substantial re-distribution of T-cells within lymphoid and non-lymphoid organs. A uniform response pattern seems to exist with a decrease in lymphocyte numbers in the spleen which is accompanied by an increase in lymphocytes in lung, bone marrow and Peyer's patches. The alterations of the migration properties could be partially explained by adrenergic mechanisms which influence surface expression of adhesion molecules. Furthermore exercise and environmental stress result in a decreased expression of adhesion molecules, which might be the result of a selective mobilization of cells. In conclusion, exercise stress induces a substantial re-distribution of T-cells within lymphoid and non-lymphoid organs. It can be hypothesized that these stress-induced effects on lymphocyte trafficking might enhance immune surveillance and vigilance. However, further investigations are crucially needed to gain more insights into the underlying mechanisms.