Body temperature and its effect on leukocyte mobilization, cytokines and markers of neutrophil activation during and after exercise

We investigated the influence of rectal temperature on the immune system during and after exercise. Ten well-trained male cyclists completed exercise trials (90 min cycling at 60% VO(2max) + 16.1 - km time trial) on three separate occasions: once in 18 degrees C and twice in 32 degrees C. Twenty minutes after the trials in 32 degrees C, the cyclists sat for approximately 20 min in cold water (14 degrees C) on one occasion, whereas on another occasion they sat at room temperature. Rectal temperature increased significantly during cycling in both conditions, and was significantly higher after cycling in 32 degrees C than in 18 degrees C (P < 0.05). Leukocyte counts increased significantly during cycling but did not differ between the conditions. The concentrations of serum interleukin (IL)-6, IL-8 and IL-10, plasma catecholamines, granulocyte-colony stimulating factor, myeloperoxidase and calprotectin increased significantly following cycling in both conditions. The concentrations of serum IL-8 (25%), IL-10 (120%), IL-1 receptor antagonist (70%), tumour necrosis factor-alpha (17%), plasma myeloperoxidase (26%) and norepinephrine (130%) were significantly higher after cycling in 32 degrees C than in 18 degrees C. During recovery from exercise in 32 degrees C, rectal temperature was significantly lower in response to sitting in cold water than at room temperature. However, immune changes during 90 min of recovery did not differ significantly between sitting in cold water and at room temperature. The greater rise in rectal temperature during exercise in 32 degrees C increased the concentrations of serum IL-8, IL-10, IL-1ra, TNF-alpha and plasma myeloperoxidase, whereas the greater decline in rectal temperature during cold water immersion after exercise did not affect immune responses.

Exercise-recruited NK cells display exercise-associated eHSP-70

It is hypothesized that increased plasma or serum concentrations of extracellular heat shock proteins (eHSP) serve as a danger signal to the innate immune system. Cellular binding of eHSP leads to activation of NK cells and monocytes, as measured by their increased cytokine production, mitotic division and killing capacity. We examined whether eHSP binds to NK lymphocytes in vivo in athletes performing endurance exercise in the heat. Eighteen trained male runners ran at 70% VO2max at 35 degrees C and 40% relative humidity. Venous blood collected before, after and 1.5 h after exercise was analysed for leukocyte distribution, phenotype and eHSP70. NK cell-enriched samples were examined for co-localization of CD94 and eHSP70 expression. Plasma eHSP-70 concentration was measured by ELISA. Subjects ran for approximately 50 min, which elicited a reversible leukocytosis. NK cell count increased 83% (p < 0.01) immediately after exercise, then decreased to 66% of the resting level 1.5 h after exercise (p < 0.05). Plasma eHSP concentration increased 167% after exercise and remained elevated (by up to 71%) 1.5 h after exercise (p < 0.01). eHSP was expressed on both NK cells and monocytes at all times; the count of NK cells positive for eHSP doubled from 0.04 +/- 0.02 10(9)/L (mean +/- SD) to 0.08 +/- 0.06 10(9)/L after exercise. In summary, exercise in the heat increased free plasma eHSP concentration, and the eHSP co-localized with CD94 on NK cells. These data confirm the link between exercise and activation of the innate immune system.

Characterization of inflammatory responses to eccentric exercise in humans

Eccentric exercise commonly results in muscle damage. The primary sequence of events leading to exercise-induced muscle damage is believed to involve initial mechanical disruption of sarcomeres, followed by impaired excitation-contraction coupling and calcium signaling, and finally, activation of calcium-sensitive degradation pathways. Muscle damage is characterized by ultrastructural changes to muscle architecture, increased muscle proteins and enzymes in the bloodstream, loss of muscular strength and range of motion and muscle soreness. The inflammatory response to exercise-induced muscle damage is characterized by leukocyte infiltration and production of pro-inflammatory cytokines within damaged muscle tissue, systemic release of leukocytes and cytokines, in addition to alterations in leukocyte receptor expression and functional activity. Current evidence suggests that inflammatory responses to muscle damage are dependent on the type of eccentric exercise, previous eccentric loading (repeated bouts), age and gender. Circulating neutrophil counts and systemic cytokine responses are greater after eccentric exercise using a large muscle mass (e.g. downhill running, eccentric cycling) than after other types of eccentric exercise involving a smaller muscle mass. After an initial bout of eccentric exercise, circulating leukocyte counts and cell surface receptor expression are attenuated. Leukocyte and cytokine responses to eccentric exercise are impaired in elderly individuals, while cellular infiltration into skeletal muscle is greater in human females than males after eccentric exercise. Whether alterations in intracellular calcium homeostasis influence inflammatory responses to muscle damage is uncertain. Furthermore, the effects of antioxidant supplements are variable, and the limited data available indicates that anti-inflammatory drugs largely have no influence on inflammatory responses to eccentric exercise. In this review, we compare local versus systemic inflammatory responses, and discuss some of the possible mechanisms regulating the inflammatory responses to exercise-induced muscle damage in humans.

Exercise-induced muscle damage, plasma cytokines and markers of neutrophil activation

Introduction: Unaccustomed eccentric exercise often results in muscle damage and neutrophil activation. We examined changes in plasma cytokines stress hormones, creatine kinase activity and myoglobin concentration, neutrophil surface receptor expression, degranulation, and the capacity of neutrophils to generate reactive oxygen species in response to in vitro stimulation after downhill running. Methods: Ten well-trained male runners ran downhill on a treadmill at a gradient of -10% for 45 min at 60% V̇O2max. Blood was sampled immediately before (PRE) and after (POST), 1 h (1 h POST), and 24 h (24 h POST) after exercise. Results: At POST, there were significant increases (P < 0.01) in neutrophil count (32%), plasma interleukin (IL)-6 concentration (460%), myoglobin (Mb) concentration (1100%), and creatine kinase (CK) activity (40%). At 1 h POST, there were further increases above preexercise values for neutrophil count (85%), plasma Mb levels (1800%), and CK activity (56%), and plasma IL-6 concentration remained above preexercise values (410%) (P < 0.01). At 24 h POST, neutrophil counts and plasma IL-6 levels had returned to baseline, whereas plasma Mb concentration (100%) and CK activity (420%) were elevated above preexercise values (P < 0.01). There were no significant changes in neutrophil receptor expression, degranulation and respiratory burst activity, and plasma IL-8 and granulocyte-colony stimulating factor concentrations at any time after exercise. Neutrophil count correlated with plasma Mb concentration at POST (r = 0.64, P < 0.05), and with plasma CK activity at POST (r = 0.83, P < 0.01) and 1 h POST (r = 0.78, P < 0.01). Conclusion: Neutrophil activation remains unchanged after downhill running in well-trained runners, despite increases in plasma markers of muscle damage.

Neutrophil activation, antioxidant supplements and exercise-induced oxidative stress

Neutrophils produce free radicals known as reactive oxygen species (ROS), which assist in the clearance of damaged host tissue. Tissue damage may occur during exercise due to muscle damage, thermal stress and ischaemia/reperfusion. When produced in excess, neutrophil-derived ROS may overwhelm the body's endogenous antioxidant defence mechanisms, and this can lead to oxidative stress. There is increasing evidence for links between oxidative stress and a variety of pathological disorders such as cardiovascular diseases, cancer, chronic inflammatory diseases and post-ischaemic organ injury. A small number of studies have investigated whether there is a link between neutrophil activation and oxidative stress during exercise. In this review, we have summarised the findings of these studies. Exercise promotes the release of neutrophils into the circulation, and some evidence suggests that neutrophils mobilised after exercise have an enhanced capacity to generate some forms of ROS when stimulated in vitro. Neutrophil activation during exercise may challenge endogenous antioxidant defence mechanisms, but does not appear to increase lipid markers of oxidative stress to any significant degree, at least in the circulation. Antioxidant supplements such as N-acetylcysteine are effective at attenuating increases in the capacity of neutrophils to generate ROS when stimulated in vitro, whereas vitamin E reduces tissue infiltration of neutrophils during exercise. Free radicals generated during intense exercise may lead to DNA damage in leukocytes, but it is unknown if this damage is the result of neutrophil activation. Exercise enhances the expression of inducible haem (heme)-oxygenase (HO-1) in neutrophils after exercise, however, it is uncertain whether oxidative stress is the stimulus for this response.

Exercise-induced alterations in neutrophil degranulation and respiratory burst activity : possible mechanisms of action

Neutrophils constitute 50-60% of all circulating leukocytes; they present the first line of microbicidal defense and are involved in inflammatory responses. To examine immunocompetence in athletes, numerous studies have investigated the effects of exercise on the number of circulating neutrophils and their response to stimulation by chemotactic stimuli and activating factors. Exercise causes a biphasic increase in the number of neutrophils in the blood, arising from increases in catecholamine and cortisol concentrations. Moderate intensity exercise may enhance neutrophil respiratory burst activity, possibly through increases in the concentrations of growth hormone and the inflammatory cytokine IL-6. In contrast, intense or long duration exercise may suppress neutrophil degranulation and the production of reactive oxidants via elevated circulating concentrations of epinephrine (adrenaline) and cortisol. There is evidence of neutrophil degranulation and activation of the respiratory burst following exercise-induced muscle damage. In principle, improved responsiveness of neutrophils to stimulation following exercise of moderate intensity could mean that individuals participating in moderate exercise may have improved resistance to infection. Conversely, competitive athletes undertaking regular intense exercise may be at greater risk of contracting illness. However, there are limited data to support this concept. To elucidate the cellular mechanisms involved in the neutrophil responses to exercise, researchers have examined changes in the expression of cell membrane receptors, the production and release of reactive oxidants and more recently, calcium signaling. The investigation of possible modifications of other signal transduction events following exercise has not been possible because of current methodological limitations. At present, variation in exercise-induced alterations in neutrophil function appears to be due to differences in exercise protocols, training status, sampling points and laboratory assay techniques.

Exercise and Cellular Mechanisms of Muscle Injury

The general aim of this book is to provide a comprehensive summary of the characteristics of exercise-induced muscle damage and the mechanisms of tissue inflammation. The authors present a large amount of our own original data and have summarised the research of others.

The ionic products from bredigite bioceramics induced cementogenic differentiation of periodontal ligament cells via activation of the Wnt/β-catenin signalling pathway

Periodontitis results from the destructive inflammatory reaction of the host elicited by a bacterial biofilm adhering to the tooth surface and if left untreated, may lead to the loss of the teeth and the surrounding tissues, including the alveolar bone. Cementum is a specialized calcified tissue covering the tooth root and an essential part of the periodontium which enables the attachment of the periodontal ligament to the root and the surrounding alveolar bone. Periodontal ligament cells (PDLCs) represent a promising cell source for periodontal tissue engineering. Since cementogenesis is the critical event for the regeneration of periodontal tissues, this study examined whether inorganic stimuli derived from bioactive bredigite (Ca7MgSi4O16) bioceramics could stimulate the proliferation and cementogenic differentiation of PDLCs, and further investigated the involvement of the Wnt/β-catenin signalling pathway during this process via analysing gene/protein expression of PDLCs which interacted with bredigite extracts. Our results showed that the ionic products from bredigite powder extracts led to significantly enhanced proliferation and cementogenic differentiation, including mineralization–nodule formation, ALP activity and a series of bone/cementum-related gene/protein expression (ALP, OPN, OCN, BSP, CAP and CEMP1) of PDLCs in a concentration dependent manner. Furthermore, the addition of cardamonin, a Wnt/β-catenin signalling inhibitor, reduced the pro-cementogenesis effect of the bredigite extracts, indicating the involvement of the Wnt/β-catenin signalling pathway in the cementogenesis of PDLCs induced by bredigite extracts. The present study suggests that an entirely inorganic stimulus with a specific composition of bredigite bioceramics possesses the capacity to trigger the activation of the Wnt/β-catenin signalling pathway, leading to stimulated differentiation of PDLCs toward a cementogenic lineage. The results indicate the therapeutic potential of bredigite ceramics in periodontal tissue engineering application.

Theoretical study of two states reactivity of methane activation on iron atom and iron dimer

Density functional theory (DFT) calculations have been carried out to explore the catalytic activation of C–H bonds in methane by the iron atom, Fe, and the iron dimer, Fe2. For methane activation on an Fe atom, the calculations suggest that the activation of the first C–H bond is mediated via the triplet excited-state potential energy surface (PES), with initial excitation of Fe to the triplet state being necessary for the reaction to be energetically feasible. Compared with the breaking of the first C–H bond, the cleavage of the second C–H bond is predicted to involve a significantly higher barrier, which could explain experimental observations of the HFeCH3 complex rather than CH2FeH2 in the activation of methane by an Fe atom. For methane activation on an iron dimer, the cleavage of the first C–H bond is quite facile with a barrier only 11.2, 15.8 and 8.4 kcal/mol on the septet state energy surface at the B3LYP/6-311+G(2df,2dp), BPW91/6-311+G(2df,2dp) and M06/B3LYP level, respectively. Cleavage of the second C–H bond from HFe2CH3 involves a barrier calculated respectively as 18.0, 10.7 and 12.4 kcal/mol at the three levels. The results suggest that the elimination of hydrogen from the dihydrogen complex is a rate-determining step. Overall, our results indicate that the iron dimer Fe2 has a stronger catalytic effect on the activation of methane than the iron atom.

Human single-stranded DNA binding proteins are essential for maintaining genomic stability

The double-stranded conformation of cellular DNA is a central aspect of DNA stabilisation and protection. The helix preserves the genetic code against chemical and enzymatic degradation, metabolic activation, and formation of secondary structures. However, there are various instances where single-stranded DNA is exposed, such as during replication or transcription, in the synthesis of chromosome ends, and following DNA damage. In these instances, single-stranded DNA binding proteins are essential for the sequestration and processing of single-stranded DNA. In order to bind single-stranded DNA, these proteins utilise a characteristic and evolutionary conserved single-stranded DNA-binding domain, the oligonucleotide/oligosaccharide-binding (OB)-fold. In the current review we discuss a subset of these proteins involved in the direct maintenance of genomic stability, an important cellular process in the conservation of cellular viability and prevention of malignant transformation. We discuss the central roles of single-stranded DNA binding proteins from the OB-fold domain family in DNA replication, the restart of stalled replication forks, DNA damage repair, cell cycle-checkpoint activation, and telomere maintenance.

ATM is required for the cellular response to thymidine induced replication fork stress

Genetically distinct checkpoints, activated as a consequence of either DNA replication arrest or ionizing radiation-induced DNA damage, integrate DNA repair responses into the cell cycle programme. The ataxia-telangiectasia mutated (ATM) protein kinase blocks cell cycle progression in response to DNA double strand breaks, whereas the related ATR is important in maintaining the integrity of the DNA replication apparatus. Here, we show that thymidine, which slows the progression of replication forks by depleting cellular pools of dCTP, induces a novel DNA damage response that, uniquely, depends on both ATM and ATR. Thymidine induces ATM-mediated phosphorylation of Chk2 and NBS1 and an ATM-independent phosphorylation of Chk1 and SMC1. AT cells exposed to thymidine showed decreased viability and failed to induce homologous recombination repair (HRR). Taken together, our results implicate ATM in the HRR-mediated rescue of replication forks impaired by thymidine treatment.

Environment and Interaction: a study in social activation of the public realm

The natural and built environment has been shown to affect its users in both psychological and physiological forms. But can if affect the sociological aspects of human processes and actions? The activation of the public realm can be shown to reduce socially dysfunctional behaviour through the simple occupation of the space and a number of other key variables through its design. In order to explore this further we must study how public space is being used in terms of social interaction, which will lead to a set of design ideals through which the social activation of public space can be achieved. Observations of differing social contexts have been undertaken in order to solidify key ideas and design principles for the activation of public space. Three sites were selected, each containing different amounts of vegetation and opportunity for occupation. These were then analysed through a lens of levels of social interaction. In this way it can become evident how the users interact with and within their social environments Through the analysis of the chosen sites, it has become evident that levels of interaction between the users, whether for transitory or occupational purposes, rise directly with vegetation and opportunity for occupation. With this in mind it can be determined that through design, public space can allow for and create greater opportunity for social interaction.

A density functional theory study on CO2 capture and activation by graphene-like boron nitride with boron vacancy

First principle calculations for a hexagonal (graphene-like) boron nitride (g-BN) monolayer sheet in the presence of a boron-atom vacancy show promising properties for capture and activation of carbon dioxide. CO2 is found to decompose to produce an oxygen molecule via an intermediate chemisorption state on the defect g-BN sheet. The three stationary states and two transition states in the reaction pathway are confirmed by minimum energy pathway search and frequency analysis. The values computed for the two energy barriers involved in this catalytic reaction after enthalpy correction indicate that the catalytic reaction should proceed readily at room temperature.

Validation and consistency in the application of a trauma team activation system at a level 1 trauma centre

- The RAH was activated over 2500 trauma calls in 2009. This figure is over twice the number of calls put out by similar services. - Many trauma calls (in particular L2 trauma calls) from the existing system do not warrant activation of the trauma team - Sometimes trauma calls are activated for nontrauma reasons (eg rapid access to radiology, departmental pressures etc) - The excess of trauma calls has several deleterious effects particularly on time management for the trauma service staff: ward rounds/tertiary survey rounds, education, quality improvement, research

Cerebral cortex activation mapping upon electrical muscle stimulation by 32-channel time-domain functional near-infrared spectroscopy

The application of different EMS current thresholds on muscle activates not only the muscle but also peripheral sensory axons that send proprioceptive and pain signals to the cerebral cortex. A 32-channel time-domain fNIRS instrument was employed to map regional cortical activities under varied EMS current intensities applied on the right wrist extensor muscle. Eight healthy volunteers underwent four EMS at different current thresholds based on their individual maximal tolerated intensity (MTI), i.e., 10 % < 50 % < 100 % < over 100 % MTI. Time courses of the absolute oxygenated and deoxygenated hemoglobin concentrations primarily over the bilateral sensorimotor cortical (SMC) regions were extrapolated, and cortical activation maps were determined by general linear model using the NIRS-SPM software. The stimulation-induced wrist extension paradigm significantly increased activation of the contralateral SMC region according to the EMS intensities, while the ipsilateral SMC region showed no significant changes. This could be due in part to a nociceptive response to the higher EMS current intensities and result also from increased sensorimotor integration in these cortical regions.