Biomedical subjects

Michael Gleeson

Publications and source records attributed to Michael Gleeson.

At least 19 recordsLinked to original sources

PubMed2006

Guidelines for the diagnosis and management of individuals with neurofibromatosis 1.

Neurofibromatosis 1 (NF1) is a common neurocutaneous condition with an autosomal dominant pattern of inheritance. The complications are diverse and disease expression varies, even within families. Progress in molecular biology and neuroimaging and the development of mouse models have helped to elucidate the aetiology of NF1 and its clinical manifestations. Furthermore, these advances have raised the prospect of therapeutic intervention for this complex and distressing disease. Members of the United Kingdom Neurofibromatosis Association Clinical Advisory Board collaborated to produce a consensus statement on the current guidelines for diagnosis and management of NF1. The proposals are based on published clinical studies and on the pooled knowledge of experts in neurofibromatosis with experience of providing multidisciplinary clinical and molecular services for NF1 patients. The consensus statement discusses the diagnostic criteria, major differential diagnoses, clinical manifestations and the present strategies for monitoring and management of NF1 complications.

Child↗

PubMed2006

The effect of 2 weeks vitamin C supplementation on immunoendocrine responses to 2.5 h cycling exercise in man.

An increased systemic concentration of stress hormones (of the hypothalamic-pituitary adrenal axis) and some cytokines may contribute to the depression of immune cell function typically observed after prolonged exercise. The aim of the present study was to determine the effect of 2 weeks of supplementation with vitamin C (VC) on cortisol, adrenocorticotrophic hormone, interleukin-6, oxidative stress and neutrophil responses to a single bout of endurance exercise. Nine healthy endurance-trained males exercised for 2.5 h at 60% VO2max after 2 weeks of placebo (PLA) or VC (1,000 mg day(-1)) supplementation. All participants completed both trials utilising a randomised crossover design with a minimum 14 day washout period between trials. There was a significant trial x time interaction effect for plasma cortisol concentration (P = 0.039) which tended to be lower in the VC trial but post hoc analysis found no specific between trial differences. There was a significantly lower post-exercise neutrophilia (P < 0.014) in the VC trial, compared with the PLA trial. There was no trial x time interaction for measures of neutrophil function (bacteria-stimulated elastase release, fMLP or PMA-stimulated oxidative burst). However, there was a trend for higher fMLP-stimulated neutrophil oxidative burst in the VC compared with PLA trial (trial x time interaction, P = 0.075). These results suggest that supplementation with VC for a period of up to 2 weeks provides little to no protection against the depression of neutrophil function which typically occurs after endurance exercise.

Adrenocorticotropic Hormone↗

PubMed2006

Immune system adaptation in elite athletes.

PURPOSE OF REVIEW: To evaluate the effects of exercise on immune function in relation to infection susceptibility. RECENT FINDINGS: Postexercise immune function depression is most pronounced when exercise is continuous, prolonged, of moderate to high intensity and performed without food intake. Periods of intensified training that result in overreaching have been shown to chronically depress immune function, with leukocyte functions measured at rest still depressed 24 h after the last exercise bout. Several studies indicate that the incidence of symptoms of upper respiratory tract illness is increased in the days following prolonged strenuous endurance events and it has been generally assumed that this is due to the temporary exercise-induced depression of immune function. More recently it has been proposed that at least some of these symptoms are attributable to inflammation of the upper respiratory tract rather than to infectious episodes. SUMMARY: Although elite athletes are not clinically immune deficient, it is possible that the combined effects of small changes in several immune parameters may compromise resistance to common minor illnesses. Although it is possible that immune depression linked with prolonged intensive training may determine susceptibility to infection, convincing evidence of a cause and effect relationship remains elusive.

Adaptation, Physiological↗

PubMed2006

Can nutrition limit exercise-induced immunodepression?

Prolonged exercise and heavy training are associated with depressed immune cell function. To maintain immune function, athletes should eat a well-balanced diet sufficient to meet their energy, carbohydrate, protein, and micronutrient requirements. Consuming carbohydrate during prolonged strenuous exercise attenuates rises in stress hormones and appears to limit the degree of exercise-induced immune depression. Recent evidence suggests that antioxidant vitamin supplementation may also reduce exercise stress and impairment of leukocyte functions. Further research is needed to evaluate the effects of other antioxidants and dietary immunostimulants such as probiotics and echinacea on exercise-induced immune impairment.

Antioxidants↗

PubMed2005

The effects of carbohydrate supplementation during the second of two prolonged cycling bouts on immunoendocrine responses.

The purpose of this study was to examine the effect of carbohydrate (CHO) feeding during the second of two 90-min cycling bouts (EX1 started at 09:00 and EX2 started at 13:30) at 60% VO2max on leucocyte redistribution, neutrophil degranulation and oxidative burst and plasma IL-6 and stress hormone responses. This study consisted of two trials, which were completed in a counterbalanced order and separated by at least 4 days. Subjects (n=9) consumed a lemon flavoured 10% w/v CHO (glucose) or placebo (PLA) beverage during EX2: 500 ml just before exercise and 250 ml every 20 min during exercise. Venous blood samples were taken 5 min before exercise, immediately post-exercise, and 18-h post-EX2 for both trials. The main findings of this study were that ingestion of CHO compared with PLA during EX2 better maintained plasma glucose concentration, blunted the responses of plasma adrenaline, ACTH, cortisol, GH and IL-6, and attenuated the leukocytosis and monocytosis, but had no effect on neutrophil degranulation and oxidative burst activity. Furthermore, the immunoendocrine disturbances induced by two bouts of prolonged exercise returned to resting values within 18 h. These findings suggest that ingestion of CHO compared with PLA during the second of two bouts of 90-min cycling at 60% VO2max better maintains plasma glucose, blunts hypothalamic-pituitary-adrenal activation, and attenuates leucocyte trafficking, but does not affect neutrophil function. Furthermore, the disturbances of immunoendocrine responses induced by two bouts of prolonged exercise on the same day recover within 18 h.

Adrenocorticotropic Hormone↗

PubMed2005

The physiological regulation of toll-like receptor expression and function in humans.

Eleven mammalian toll-like receptors (TLRs 1-11) have been identified to date and are known to play a crucial role in the regulation of immune responses; however, the factors that regulate TLR expression and function in vivo are poorly understood. Therefore, in the present study, we investigated the physiological regulation of TLR expression and function in humans. To examine the influence of diurnal rhythmicity on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers (n = 8) at time points coinciding with the peak and nadir in the endogenous circulating cortisol concentration. While no diurnal rhythmicity in the expression of TLRs 1, 2, 4 or 9 was observed, the upregulation of costimulatory (CD80 and CD86) and antigen-presenting (MHC class II) molecules on CD14(+) monocytes following activation with specific TLR ligands was greater (P < 0.05) in samples obtained in the evening compared with the morning. To examine the influence of physical stress on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers (n = 11) at rest and following 1.5 h of strenuous exercise in the heat (34 degrees C). Strenuous exercise resulted in a decrease (P < 0.005) in the expression of TLRs 1, 2 and 4 on CD14(+) monocytes. Furthermore, the upregulation of CD80, CD86, MHC class II and interleukin-6 by CD14(+) monocytes following activation with specific TLR ligands was decreased (P < 0.05) in samples obtained following exercise compared with at rest. These results demonstrate that TLR function is subject to modulation under physiological conditions in vivo and provide evidence for the role of immunomodulatory hormones in the regulation of TLR function.

Adaptation, Physiological↗

PubMed2005

Markers to measure immunomodulation in human nutrition intervention studies.

Normal functioning of the immune system is crucial to the health of man, and diet is one of the major exogenous factors modulating individual immunocompetence. Recently, nutrition research has focused on the role of foods or specific food components in enhancing immune system responsiveness to challenges and thereby improving health and reducing disease risks. Assessing diet-induced changes of immune function, however, requires a thorough methodological approach targeting a large spectrum of immune system parameters. Currently, no single marker is available to predict the outcome of a dietary intervention on the resistance to infection or to other immune system-related diseases. The present review summarises the immune function assays commonly used as markers in human intervention studies and evaluates their biological relevance (e.g. known correlation with clinically relevant endpoints), sensitivity (e.g. within- and between-subject variation), and practical feasibility. Based on these criteria markers were classified into three categories with high, medium or low suitability. Vaccine-specific serum antibody production, delayed-type hypersensitivity response, vaccine-specific or total secretory IgA in saliva and the response to attenuated pathogens, were classified as markers with high suitability. Markers with medium suitability include natural killer cell cytotoxicity, oxidative burst of phagocytes, lymphocyte proliferation and the cytokine pattern produced by activated immune cells. Since no single marker allows conclusions to be drawn about the modulation of the whole immune system, except for the clinical outcome of infection itself, combining markers with high and medium suitability is currently the best approach to measure immunomodulation in human nutrition intervention studies. It would be valuable to include several immune markers in addition to clinical outcome in future clinical trials in this area, as there is too little evidence that correlates markers with global health improvement.

Aging↗

PubMed2005

The effects of carbohydrate supplementation during repeated bouts of prolonged exercise on saliva flow rate and immunoglobulin A.

The purpose of this study was to assess the effect of carbohydrate (CHO) feeding during different periods of two 90-min cycling bouts (the first bout began at 09:00?h and the second bout began at 13:30 h) at 60% maximal oxygen uptake(VO2max) on saliva flow rate and saliva immunoglobulin A (sIgA) responses to the second exercise bout. The study consisted of three investigations: carbohydrate supplementation during (1) the first hour of the recovery interval (CHO-REC), (2) during the first bout of exercise and (3) during the second bout of exercise. Each investigation included two trials completed in a counterbalanced order and separated by at least 4 days. Participants consumed a lemon-flavoured 10% w/v carbohydrate beverage or placebo (22 ml.kg-1 body mass) in the first hour of the recovery interval (n=8) and 500 ml just before exercise, followed by 250 ml every 20 min during exercise in the first (n=9) and second exercise bouts (n=9). Timed unstimulated saliva samples were collected at 10 min before exercise, after 48-50 min of exercise and during the last 2 min of exercise, at 1 h post exercise, 2 h post exercise (first exercise bout only), and 18 h post exercise (second exercise bout only). Venous blood samples were taken 5 min before exercise and immediately after exercise for both exercise bouts in all trials. The main findings of the present study were as follows. First, carbohydrate ingestion during both exercise bouts, but not during the recovery interval, better maintained plasma glucose concentrations and attenuated the increase in plasma adrenaline and cortisol concentrations after the second exercise bout compared with placebo. Second, carbohydrate feeding had no effect on saliva flow rate and sIgA secretion rate compared with placebo. Third, saliva flow rate and sIgA concentration returned to pre-exercise bout 1 values within 2 h in all trials. Fourth, there was no delayed effect of exercise on oral immunity. These findings suggest that carbohydrate ingestion during the first or second bout of exercise, but not during the recovery interval, is likely to better maintain plasma glucose concentrations and attenuate the responses of plasma stress hormones to a second exercise bout than ingestion of fluid alone. Two bouts of 90 min cycling at 60% VO2max on the same day appears to inhibit saliva flow rate during the second exercise bout but does not alter sIgA transcytosis. Our results show that carbohydrate ingestion during any period of two prolonged exercise bouts does not induce different effects on oral immunity compared with placebo.

Adult↗

PubMed2005

Interrelationship between physical activity and branched-chain amino acids.

Some athletes can have quite high intakes of branched-chain amino acids (BCAAs) because of their high energy and protein intakes and also because they consume protein supplements, solutions of protein hydrolysates, and free amino acids. The requirement for protein may actually be higher in endurance athletes than in sedentary individuals because some amino acids, including the BCAAs, are oxidized in increased amounts during exercise compared with rest, and they must therefore be replenished by the diet. In the late 1970s, BCAAs were suggested to be the third fuel for skeletal muscle after carbohydrate and fat. However, the majority of later studies, using various exercise and treatment designs and several forms of administration of BCAAs (infusion, oral, and with and without carbohydrates), have failed to find a performance-enhancing effect. No valid scientific evidence supports the commercial claims that orally ingested BCAAs have an anticatabolic effect during and after exercise in humans or that BCAA supplements may accelerate the repair of muscle damage after exercise. The recommended protein intakes for athletes (1.2 to 1.8 g . kg body mass(-1) . d(-1)) do not seem to be harmful. Acute intakes of BCAA supplements of about 10-30 g/d seem to be without ill effect. However, the suggested reasons for taking such supplements have not received much support from well-controlled scientific studies.

Adult↗

PubMed2005

Assessing immune function changes in exercise and diet intervention studies.

PURPOSE OF REVIEW: To discuss the advantages and limitations of the methods currently available to assess changes in human immune function in response to interventions such as changes in diet or exercise. RECENT FINDINGS: Much recent research has focused on the effect of regular moderate exercise and the role of foods or specific food components in enhancing immune system responsiveness to challenge and thereby improving health and reducing disease risk. The present review summarizes the issues in experimental design that need to be considered in human intervention studies, the immune function variables commonly used as markers in such studies and the biological relevance (e.g. known correlation with clinically relevant endpoints) of the markers. In-vivo markers appear to be the best. Markers of peripheral blood leukocyte function are also of value since they may provide information on the mechanism(s) of change caused by an intervention. SUMMARY: Currently, no single marker of human immune function is available to predict the outcome of an exercise or dietary intervention on the resistance to infection or to other immune system-related diseases. There is too little evidence at present that correlates individual markers with global health improvement and therefore assessing changes of immune function requires a thorough methodological approach targeting a large spectrum of parameters.

Biomarkers↗

PubMed2005

Influence of acute vitamin C and/or carbohydrate ingestion on hormonal, cytokine, and immune responses to prolonged exercise.

The aim of the present study was to investigate the effect of vitamin C with or without carbohydrate consumed acutely in beverages before and during prolonged cycling on immunoendocrine responses. In a single blind, randomized manner six healthy, moderately trained males exercised for 2.5 h at 60% VO(2max)and consumed either placebo (PLA), carbohydrate (CHO, 6% w/v), vitamin C (VC, 0.15% w/v) or CHO+VC beverages before and during the bouts; trials were separated by 1 wk. CHO and CHO+VC significantly blunted the post-exercise increase in plasma concentrations of cortisol, ACTH, total leukocyte, and neutrophil counts and limited the decrease in plasma glucose concentration and bacteria-stimulated neutrophil degranulation. VC increased plasma antioxidant capacity (PAC) during exercise (P < 0.05) but had no effect on any of the immunoendocrine responses (P > 0.05). CHO+VC increased PAC compared to CHO but had no greater effects,p above those observed with CHO alone, on any of the immunoendocrine responses. In conclusion, acute supplementation with a high dose of VC has little or no effect on the hormonal, interleukin-6, or immune response to prolonged exercise and combined ingestion of VC with CHO provides no additional effects compared with CHO alone.

Adrenocorticotropic Hormone↗

PubMed2005

The T cell and NK cell immune response to exercise.

Exercise elicits an increase in the numbers of circulating lymphocytes and lymphocyte subsets (including NK cells) which is followed by a decrease in the numbers of cells during recovery from exercise; this lymphocytopenia appears to be due to a decrease in the percentage of type 1 T cells and NK cells in the circulation at this time. A decrease in mitogen-stimulated T cell proliferation and T cell production of IL-2 and IFN-gamma is reported immediately after acute, intensive exercise. NK cell cytolytic activity per cell (NKCA) does not appear to change much after exercise unless the bout was prolonged, intense and stressful, in which case NKCA can be depressed for several hours. Resting immune function is not very different in athletes compared with non-athletes. However, periods of intensified training in already well trained athletes can result in a depression of immunity in the resting state which may be due to the cumulative effects of repeated bouts of intense exercise with the consequent elevation of stress hormones, particularly cortisol and anti-inflammatory cytokines (e.g. IL-6, IL-10, IL-Ira) causing temporary inhibition of type 1 T cell cytokine production with a relative dampening of the type I (cell-mediated) response.

Exercise↗

PubMed2004

Effects of carbohydrate supplementation on performance and carbohydrate oxidation after intensified cycling training.

To study the effects of carbohydrate (CHO) supplementation on performance changes and symptoms of overreaching, six male endurance cyclists completed 1 wk of normal (N), 8 days of intensified (ITP), and 2 wk of recovery training (R) on two occasions in a randomized crossover design. Subjects completed one trial with a 6% CHO solution provided before and during training and a 20% solution in the 1 h postexercise (H-CHO trial). On the other occasion, subjects consumed a 2% CHO solution at the same time points (L-CHO). A significant decline in time to fatigue at approximately 63% maximal power output (H-CHO: 17 +/- 3%; L-CHO: 26 +/- 7%) and a significant increase in mood disturbance occurred in both trials after ITP. The decline in performance was significantly greater in the L-CHO trial. After ITP, a significant decrease in estimated muscle glycogen oxidation (H-CHO: N 49.3 +/- 2.9 kcal/30 min, ITP 32.6 +/- 3.4 kcal/30 min; L-CHO: N 49.1 +/- 30 kcal/30 min, ITP 39.0 +/- 5.6 kcal/30 min) and increase in fat oxidation (H-CHO: N 16.3 +/- 2.4 kcal/30 min, ITP 27.8 +/- 2.3 kcal/30 min; L-CHO: N 16.9 +/- 2.6 kcal/30 min, ITP: 25.4 +/- 3.5 kcal/30 min) occurred alongside significant increases in glycerol and free fatty acids and decreases in free triglycerides in both trials. An interaction effect was observed for submaximal plasma concentrations of cortisol and epinephrine, with significantly greater reductions in these stress hormones in L-CHO compared with H-CHO after ITP. These findings suggest that CHO supplementation can reduce the symptoms of overreaching but cannot prevent its development. Decreased endocrine responsiveness to exercise may be implicated in the decreased performance and increased mood disturbance characteristic of overreaching.

Adult↗

PubMed2004

Exercise, nutrition and immune function.

Strenuous bouts of prolonged exercise and heavy training are associated with depressed immune cell function. Furthermore, inadequate or inappropriate nutrition can compound the negative influence of heavy exertion on immunocompetence. Dietary deficiencies of protein and specific micronutrients have long been associated with immune dysfunction. An adequate intake of iron, zinc and vitamins A, E, B6 and B12 is particularly important for the maintenance of immune function, but excess intakes of some micronutrients can also impair immune function and have other adverse effects on health. Immune system depression has also been associated with an excess intake of fat. To maintain immune function, athletes should eat a well-balanced diet sufficient to meet their energy requirements. An athlete exercising in a carbohydrate-depleted state experiences larger increases in circulating stress hormones and a greater perturbation of several immune function indices. Conversely, consuming 30-60 g carbohydrate x h(-1) during sustained intensive exercise attenuates rises in stress hormones such as cortisol and appears to limit the degree of exercise-induced immune depression. Convincing evidence that so-called 'immune-boosting' supplements, including high doses of antioxidant vitamins, glutamine, zinc, probiotics and Echinacea, prevent exercise-induced immune impairment is currently lacking.

Exercise↗

PubMed2004

The effect of single and repeated bouts of prolonged cycling on leukocyte redistribution, neutrophil degranulation, IL-6, and plasma stress hormone responses.

This study compared immunoendocrine responses to a single bout of prolonged cycling at different times of day and to a 2nd bout of cycling at the same intensity on the same day. In a counterbalanced design, 8 men participated in 3 experimental trials separated by at least 4 d. In the afternoon exercise-only trial, subjects cycled for 2 h at 60% VO2max starting at 14:00. In the other 2 trials, subjects performed either 2 bouts of cycling at 60% VO2max for 2 h (starting at 09:00 and 14:00) or a separate resting trial. The single bout of prolonged exercise performed in the afternoon induced a larger neutrophilia and monocytosis than the identical bout of morning exercise, possibly the result of reduced carbohydrate availability and the circadian rhythm in cortisol levels. The 2nd prolonged exercise bout caused greater immunoendocrine responses but lower plasma glucose levels and neutrophil function compared with the 1st bout.

Adrenocorticotropic Hormone↗

PubMed2004

The effects of pre-exercise high carbohydrate meals with different glycemic indices on blood leukocyte redistribution, IL-6, and hormonal responses during a subsequent prolonged exercise.

The purpose of this study was to determine the effect of pre-exercise high carbohydrate meals with high glycemic index (HGI) or low glycemic index (LGI) on blood leukocyte redistribution during subsequent endurance exercise. Eight male subjects performed a 90-min run on a treadmill at 70 % VO2max 3 h after ingesting an isocaloric HGI or LGI meal with GI values of 77 and 37, respectively. Blood counts of leukocytes, and neutrophils and the neutrophil/lymphocyte ratio were significantly lower in LGI than HGI at 90 min of exercise (P < 0.05). The plasma glucose concentrations were significantly higher in LGI than HGI between 15 min and 45 min of exercise. There were, however, no differences in plasma cortisol, growth hormone, and interleukin-6 concentrations between trials. Thus, the GI of a pre-exercise meal influences leukocyte trafficking and plasma glucose but has limited effects on circulating stress hormone and cytokine responses to exercise.

Adult↗

PubMed2004

Effects of acute exhaustive exercise and chronic exercise training on type 1 and type 2 T lymphocytes.

The present study examined the effects of acute exhaustive exercise and chronic exercise training on type 1 and type 2 T lymphocyte distribution and intracellular cytokine production. Seven endurance-trained male cyclists completed exercise trials to exhaustion before, immediately after, and following 2 weeks of resting recovery from a 6-day intensified training period (ITP). During each trial, resting and post-exercise blood samples were incubated with phorbol 12-myristate 13-acetate (PMA) and ionomycin and stained for T lymphocyte surface antigens (CD3). Cells were then permeabilised, stained for intracellular cytokines and analysed using flow cytometry. Acute exhaustive exercise before and following 2 weeks of recovery from the ITP, but not immediately after the ITP, significantly reduced the circulating percentage and number of lFN-gamma+ (type 1) T cells (P<0.05). In addition, the amount of IFN-gamma produced by stimulated T lymphocytes was decreased (P<0.05) post-exercise during each trial. The percentage and number of interferon (IFN)-gamma+ T lymphocytes was decreased (P<0.05) at rest immediately after the ITP compared with before and following 2 weeks of resting recovery from the ITP. However, the amount of IFN-gamma produced by stimulated T lymphocytes at rest was unaltered following the ITP. Neither acute exercise nor chronic exercise training caused an alteration in the circulating percentage or number of interleukin (IL)-4+ (type 2) T lymphocytes. These results suggest a possible mechanism for the increased incidence of infection reported during chronic exercise training via modulation of type 1/type 2 T lymphocyte distribution.

Adult↗

PubMed2003

Effect of pre-exercise carbohydrate ingestion on plasma cytokine, stress hormone, and neutrophil degranulation responses to continuous, high-intensity exercise.

The purpose of the present study was to examine the effect of pre-exercise carbohydrate (CHO) ingestion on circulating leukocyte numbers, plasma interleukin (IL)-6, plasma cortisol, and lipopolysaccharide (LPS)-stimulated neutrophil degranulation responses in moderately trained male cyclists who completed approximately 1-h of high-intensity cycling. The influence of the timing of pre-exercise CHO ingestion was investigated in 8 subjects who consumed 75 g CHO as a glucose solution at either 15 (-15 trial), or 75 (-75 trial) min before the onset of exercise. The influence of the amount of pre-exercise CHO ingestion was investigated in a further 10 subjects who consumed either 25 g or 200 g CHO as a glucose solution or a placebo 45 min before the onset of exercise. At the onset of exercise in the timing experiment, the plasma glucose concentration was significantly (p < .05) lower on the -75 trial compared with pre-drink values, and the plasma cortisol concentration and neutrophil to lymphocyte (N/L) ratio were significantly (p < .05) elevated in the post-exercise period. In the -15 trial, plasma glucose level was well maintained, and the plasma cortisol concentration and N/L ratio were not significantly elevated above resting levels. However, LPS-stimulated neutrophil degranulation was similar in the -15 and -75 trials. The amount of CHO ingested had no effect on the magnitude of the rise in the N/L ratio compared with placebo when consumed 45 min pre-exercise. Finally, although an exercise-induced increase in the plasma IL-6 concentration was observed, this effect was independent of pre-exercise CHO ingestion.

Adult↗