The cross-sectional Biomarkers Study was undertaken in Canberra, Australia (2000-2002) to examine the role of psychosocial factors in the socioeconomic health gradient, via physiological changes consequent upon activation of the neuroendocrine stress response.¶ The study population was derived from healthy 40-44 year old men and women already participating in a longitudinal cohort study. Using data from the cohort study, four groups with similar occupational status were formed. The study sample was randomly selected within these groups, thus representing the socioeconomic spectrum.¶ A pilot study involved 60 participants with blood and saliva samples measured on two occasions. A further 302 people had blood and saliva samples taken on one occasion. Socioeconomic status was measured by occupational code and status, personal and household income, education and perceived position in the community and in Australia. Psychosocial and behavioural factors, including job strain, job security, coping style, anxiety, depression, optimism, self-esteem, sense of belonging and trust, social support, smoking, exercise and alcohol intake were assessed by selfreport. Five biological parameters: plasma fibrinogen, glycated haemoglobin, waisthip ratio, serum neopterin and salivary IgA were measured as outcome variables.Three hypotheses were tested:¶ 1. There is a socioeconomic gradient in measures of psychosocial stress, and of psychological resilience.¶ 2. There is a socioeconomic gradient in biological measures that have a plausible¶ association with future disease. 3. Psychosocial factors mediate the demonstrated association between socioeconomic status and the biological measures.¶ Data analysis confirmed a socioeconomic gradient in some psychosocial and behavioural variables: economic strain (r=-0.44, p&lt0.001), job demands (r=0.45, p&lt0.001), job control (r=0.26, p&lt0.001), active coping style (r=0.28, p &lt0.001), sense of optimism (r=0.24, p&lt0.001), social capital (r=0.26, p&lt0.001), job security (r=0.17, p=0.002), job marketability (r=-0.16, p=0.005), sense of belonging (r=0.22, p&lt0.001), number of adverse life events (r=-0.13, p=0.01) and positive interaction with family and friends (r=0.20, p&lt0.001 ), vigorous physical activity (r=-0.16, p=0.002), alcohol consumption (r=0.30, p&lt0.001) and smoking status (r=-0.25, p&lt0.001). There was no socioeconomic gradient in anxiety, depression, neuroticism, hostility, locus of control, self-esteem, perceived stress or mental health (SF-12). Four of the five biological markers varied with socioeconomic status: plasma fibrinogen (female (F): r=-0.26, p=0.002, male (M) r=-0.08, p=0.30), glycated haemoglobin (F: r=-0.23, p=0.01, M: r=-0.11, p=0.17), waist-hip ratio (F: r=-0.19, p=0.03, M: r=-0.27, p&lt0.001), serum neopterin (F: r=-0.21, p=0.009, M: r=-0.04, p=0.56), salivary IgA (F: r=-0.07, p=0.38, M: r=0.004, p=0.97). A more adverse biological profile was associated with lower socioeconomic status. Work characteristics, coping style, smoking and exercise were particularly important mediators of the association between the biological markers and socioeconomic status. Particular psychosocial factors were consistent mediators of the association between specific biomarkers and socioeconomic status (with little variation for different measures of socioeconomic status). However, the particular psychosocial factors providing significant mediation varied for the different markers.¶ In this sample of healthy 40-44 year olds, four out of five biological markers showed moderate socioeconomic variation with a more favourable profile associated with higher SES. The data provide limited support for the importance of psychosocial factors in the socioeconomic health gradient.

Early during an immune response, dendritic cells (DC) interact closely with CD4+ T cells, and cross-talk between these cells can come in the form of tumour necrosis factor (TNF) superfamily ligand-receptor interactions. These signals are critical for the maturation, function and survival of DC, and thereby dictate the capacity of DC to prime a robust T cell response. Among these cues, helper T cell-expressed CD40L interaction with DC-expressed CD40 is required to fully mature DC for cross-priming of help-dependent CD8+ T cell responses. The lymphotoxin-beta receptor (LTβR) is another TNF family receptor on DC, and it’s ligands LTα1β2 and LIGHT are expressed on activated T cells. Since abrogated LTβR signaling impairs T cell immunity, we have examined whether LTαβ represents another possible helper T cell-derived cue for full DC maturation. However the LT pathway controls lymphoid tissue organization and DC homeostasis, a second possible mechanism explaining the necessity of LTβR signaling for T cell immunity. Here we dissect the role of helper T cell-expressed LTβR ligands and DC-intrinsic LTβR signaling, independent of DC homeostasis or lymphoid organization, in DC function and T cell immunity. Absence of LTα1β2 and not LIGHT on helper T cells results in compromised T cell priming by DC ex vivo, and LTβ-/- CD4+ T cell responses are impaired in vivo. Ag-specific CD4+ T cell-expressed LTα1β2 and DC-intrinsic LTβR signaling are required for an optimal cytotoxic T lymphocyte (CTL) response in vivo. While CD40 induces IL-12 and is required for CTL function, DC-intrinsic LTβR signaling is necessary for CTL activation and expansion, early up-regulation of CD86 and IFNα/β production. Our results reveal non-redundant roles for distinct TNF family receptors in enabling DC to program different features in Ag-specific CD8+ T cells.

The purpose of this study was to evaluate the effectiveness of a whey protein isolate (WPI), a reported glutathione (GSH) booster, on exercise performance, immune function, and antioxidant status during weight maintenance and energy restriction in humans. Twenty well-trained, college age, male cyclists performed a cycling exercise test for 45 min, the first 7 min at 70% of VO2peak and the remaining 38 min at 55% VO₂peak immediately followed by a performance test set at 90% VO2peak until exhaustion. Blood samples were collected prior to the exercise test, after 45 min of exercise, within 5 min of exhaustion, and 1 h after exercise. Blood samples were analyzed for GSH, GSH/GSSG ratio, glutathione peroxidase (GPx), lipid hydroperoxides (LPO), phagocytosis, oxidative burst, peripheral blood mononuclear cell (PBMC) proliferation, and PBMC phenotyping. Subjects consumed 40g/day of WPI or casein placebo (P) along with their normal diet for 2 wk, repeated the exercise test, and then began a low energy period continuing the same supplementation for 4 d before the final exercise test. WPI was not associated with superior exercise performance or antioxidant status following exercise or weight loss. WPI supplementation did result in 33% greater lymphocyte proliferation capacity following exercise. Following exhaustive exercise for all trials, tGSH and GPx increased 7% and 11%, respectively, while WBCGSH decreased 13%. For WPI, GPx activity was 10% lower than P following exhaustive exercise for all trials combined. Weight loss (2.67 ± 0.26 kg) resulted in increases in phagocytosis (65%), white blood cell (WBC) GSH (40%), and GPx (35%) while decreasing the GSH/GSSG ratio (55%) and LPO (16%). Exhaustive exercise caused a 28% increase in CD8+ PBMCs and decreased CD4+ (34%), CD3+ (15%), the CD4+/8+ ratio (45%), and phagocytosis (8%) with all values returning to baseline after 1 h recovery. Supplementation with WPI did not enhance GSH status or exercise performance in trained cyclists, during weight maintenance or energy restriction. Following exercise, WPI is associated with greater lymphocyte proliferation of PBMCs which may help maintain an athlete's health during heavy training or competition. / Ph. D.

Health disparities, including higher rates of mental or physical illness, are found among members of minority or marginalized groups including people who identify as lesbian, gay, bisexual or transgender. However, there is a paucity of research incorporating both experiential components and measures of physical health, particularly among trans men during their transition from female to male. Trans men transition through the use of testosterone therapy (T) and surgical procedures in order to align their internal male gender identities with their physical presentation. This study combines the analysis of qualitative and quantitative data in order to understand trans men's experience of their changing bodies, identify the primary stressors faced during different stages of transition, and measure the biological manifestation of psychosocial stress during transition. Sixty-five trans men who were utilizing testosterone (T), participated in this cross-sectional study of stress experience during transition. The study involved in-depth, in-person interviews and multiple biological measures including: 24-hours of blood pressure monitoring, three consecutive days of salivary sampling for measures of cortisol and testosterone, a blood-spot for measures of C-reactive protein (CRP), and anthropometric measures. The general hypothesis for this study was that men in earlier, more liminal stages of transition would experience more transition and gender-related stress than men later in the process and that this stress would manifest experientially, psychologically, and physiologically. As expected, transition-specific psychosocial stress was associated with physiological measures, and was more pronounced among trans men in the liminal stages of transition. Moreover, comparisons of stress experience during different stages of transition uncovered variation in how trans men perceived and experienced changes in their bodies and social identity. A number of experiential aspects of transition were identified from the qualitative interviews and found to be linked to physiological stress measures including decreased nocturnal decline in blood pressure, increased cortisol levels, and increased C-reactive protein (CRP). In particular, issues related to transitioning identity stress (TIS), challenges linked to "passing" and being "out" as transgender, and specific acute stressors including the use of gender-specific public restrooms were each found to be independently associated with biological measures of stress.

A growing body of evidence has demonstrated that soy isoflavone consumption may protect against the development of various chronic diseases. This defense could be linked to isoflavone-induced alterations in immune function. However, to date, no study has examined the effect of soy isoflavone supplementation on human immunity in vivo. Establishing whether isoflavones affect immunity in aging adults is particularly relevant since compromised immune function has been observed in this population. Therefore, the purpose of this double-blind, placebo-controlled, 4-wk intervention trial was to investigate whether supplementation with soy isoflavones influenced the distribution and/or function of specific lymphocytes in postmenopausal women. Healthy postmenopausal women (50-69 y), who were not using hormone replacement therapy, were randomly divided into 2 treatment groups. The experimental group (n=9) consumed two-50 mg soy isoflavone tablets/d for 4 wk, while the control group (n=9) received placebo tablets. Fasting blood samples were drawn at baseline and on d 28 to assess distribution of T-helper cells (CD3+CD4+), T-cytotoxic cells (CD3+CD8+), total T lymphocytes (CD3+), B lymphocytes (CD19+) and natural killer (NK) cells (CD16+CD56+) via flow cytometry. Cytotoxicity of NK cells was quantified based on lactate dehydrogenase release of lysed K562 cancer cells following co-culture with NK cells from subjects. Analysis of plasma isoflavone concentrations by HPLC demonstrated a significant increase (p<0.005) in plasma genistein concentration in the experimental group after 4 wk of supplementation. However, there was no alteration in lymphocyte distribution or NK cell activity in response to isoflavone supplementation, suggesting that short-term soy isoflavone supplementation does not alter these parameters of immunity in healthy postmenopausal women. / Master of Science

No description available.

Prolonged exercise has been associated with depressed immune function, and hence an increased risk of infection. However, several nutritional supplements may reduce or overcome this problem. Thus, the aims of this thesis were to investigate the effects of some nutritional supplements on athletes immune function. In study 1 (Chapter 3), effects of several vaccine stimulant dose on whole blood culture cytokine production was carried out to determine effective vaccine stimulant dose; which was found to be between a dilution of 4000 (dose 4) and 1000 (dose 6) of the original vaccine. This finding was used for the other studies (Chapter 4 and 5). In addition, the relationship between data obtained from Evidence Investigator analyser and enzyme linked-immuno-sorbent assay (ELISA) for IL-10 was analysed and the results show a positive strong correlation between them. In study 2 (Chapter 4), in vitro effects of various immunomodulatory nutritional compounds on antigen-stimulated whole blood culture cytokine production was investigated and it was found that caffeine and quercetin showed tendency towards decrease cytokine production as the doses were increased. On the other hand, an upward trend was evident with kaloba, where high dose of kaloba seemed to increase the cytokine production. Since kaloba appeared to act as an immunostimulant in vitro, its effects on the immune response to prolonged exercise were examined in study 3 (Chapter 5). However, 7 days kaloba supplementation (20 mg of the root extract) did not alter athletes immune response although prolonged moderate intensity exercise significantly decreased S-IgA secretion rate and concentration post-exercise with the values returning to baseline by 1 h post-exercise. A 14-strain probiotic supplement effects on salivary antimicrobial proteins at rest and in response to an acute bout of prolonged exercise was investigated in study 4 (Chapter 6). Unfortunately, 30 days supplementation of the 14-strain probiotic appeared not enough to induce any significant effects on salivary antimicrobial proteins. Lastly, in study 5 (Chapter 7), the effects of a Lactobacillus probiotic on healthy people, who tend to have a higher than normal incidence of infection due to exercise stress-induced immune impairment was studied. In summary, this 16-week intervention study on 267 athletes found that regular ingestion of the probiotic reduced the extent to which training was negatively affected in endurance athletes when infection was present, and increased both S-IgA concentration and secretion rate over time. But it did not appear to reduce URTI incidence or the duration and severity of URTI episodes. Two major confounding factors, namely the unexpectedly low incidence of URTI during the winter period and the lower baseline S-IgA in the probiotic group may have prevented potential beneficial effects of probiotic supplementation from being identified.

O período de transição nas vacas leiteiras é caracterizado por alterações fisiológicas como redução de consumo, balanço energético negativo, lipólise e perda de peso, hipocalcemia, queda na função imune e contaminação bacteriana do útero. O estudo avaliou o efeito de duas aplicações de vitamina ADE intramuscular sobre o perfil bioquímico, metabolismo oxidativo e a função de leucócitos polimorfonucleares de vacas holandesas multíparas e primíparas, com dieta a base de silagem de milho e concentrado, no período de transição. Foram utilizados 32 vacas holandesas, randomizadas em dois grupos, sendo que o grupo tratado recebeu vitaminas ADE (270.000 UI vitamina A, 80.000 UI vitamina D e 80 mg vitamina E/mL) na dose de 1mL/50 kg pela via intramuscular profunda, aos 20 e 10 dias antes do parto. Aos -20d;-10d; 0d; 7d; 14d; 28 dias do parto foram colhidas amostras de sangue para análise. As alterações fisiológicas do parto foram evidenciadas pelas variáveis: habilidade de redução férrica plasmática, glicose, ácidos graxos não esterificados, colesterol, aspartato aminotransferase, gamaglutamil transferase e creatinoquinase. O período de transição interferiu tanto na produção de espécies reativas a oxigênio (EROs) quanto na porcentagem de leucócitos polimorfonucleares (PMN) fagocitando sob estímulo de Staphylococcus aureus conjugada com iodeto de propídio (SAPI). Vacas primíparas apresentaram menor desafio metabólico que as vacas multíparas, demonstrado pelos maiores valores da atividade de superóxido dismutase e concentrações plasmáticas de glicose, e menores valores de betahidroxibutirato e gamaglutamil transferase nas primíparas. Além disso, as vacas primíparas apresentaram maior porcentagem de PMN fagocitando e maior produção de EROs frente ao estímulo da SAPI. A suplementação parenteral com vitaminas ADE, na dose utilizada, não foi suficiente para melhorar o status antioxidante das vacas, independente do número de partos, porém a suplementação aumentou a produção de EROs pelos leucócitos PMN quando estimulados com lipopolissacarídeos de Escherichia coli (LPS). / The transition period in dairy cattle is characterized by physiological changes such as reduced feed intake, negative energy balance, weight loss and lipolysis, hypocalcemia, reduced immune function and bacterial contamination of the uterus. This study evaluate the effect of two applications of intramuscular vitamin ADE on the biochemical profile, oxidative metabolism and function of polymorphonuclear leukocytes of primiparous and multiparous Holstein cows with diet based on corn silage and concentrate during the transition period. Thirty-two Holstein cows, randomized into two groups, the treatment group received vitamins ADE (270,000 IU vitamin A, 80,000 IU vitamin D and vitamin E 80 mg/mL) at a dose of 1mL/50 kg by intramuscular injection, at 20 and 10 days before calving. At -20d, -10d, 0d, 7d, 14d, 28 days of postpartum blood samples were collected for analysis. Physiological changes of calving were evidenced in the following variables: ferric reducing ability of plasma, glucose, nonesterified fatty acids, cholesterol, aspartate aminotransferase, gammaglutamil transferase and creatine kinase. Furthermore the transition period interfered in the production of reactive oxygen species (ROS) and the percentage of polymorphonuclear leukocytes (PMN) phagocytosing under stimulus Staphylococcus aureus conjugated with propidium iodide (SAPI). Primiparous dairy cows had lower metabolic challenge that multiparous, demonstrated by higher values of the activity of superoxide dismutase and glucose concentrations, and lower values of betahydroxybutyrate and gammaglutamil transferase in primiparous. Moreover, primiparous cows had higher percentages of phagocytosing PMN and increased production of ROS with SAPI stimulus. Parenteral supplementation with vitamins ADE was not sufficient to improve the antioxidant status of cows, regardless of the number of calving, but supplementation increased the production of ROS by PMN leucocytes when stimulated with lipopolysaccharide of Escherichia coli (LPS).

This thesis is an investigation of the interactions of insulin resistance (IR), metabolic markers, neutrophil function, and reproductive health in peripartum dairy cows, including the evaluation of a hand-held glucometer for diagnosis of IR. The neutrophil functions of interest were oxidative burst and phagocytosis capacity, and reproductive diseases were endometritis and cervicitis. A total of 81 Holstein cows were enrolled 3 wk prior to expected calving date from November 2010 until October 2011, and were followed until 5 wk postpartum. Known markers of IR, neutrophil function, and disease were monitored through this period. The hand-held glucometer was identified as a useful alternative to laboratory measurements of glucose. Markers of IR influenced phagocytosis capacity and reproductive disease. High haptoglobin concentrations were associated with increased risk of reproductive disease and diminished oxidative burst function. Metabolically related inhibition of neutrophil function may be important in development of reproductive disease. / National Sciences and Engineering Research Council of Canada, Ontario Graduate Scholarship Program

Apart from motor and sensory function loss, an injury to the spinal cord can cause sympathetic dysfunction, which has been shown to affect immune responses. In this thesis, data from five experimental studies have been collected to compare physiological and psychophysiological exercise responses between wheelchair athlete subgroups with different disabilities (tetraplegic, paraplegic, and non-spinal cord-injured). In two preparatory studies, physiological exercise responses to exhaustive (Chapter 4) and submaximal exercise (Chapter 5) were investigated in all three disability subgroups. Whilst reliability measures for peak oxygen uptake (VO2peak) were in a range observed previously in able-bodied athletes, the variation in tetraplegic athletes was larger when expressed relative to their VO2peak, questioning the use of this variable to track small changes in aerobic capacity in athletic populations. Submaximal physiological and psychophysiological exercise responses were found to be similar between disability subgroups when expressed as a percentage of VO2peak, justifying the protocol used in the laboratory study on mucosal immune function, which was based on the same percentages of VO2peak for all disability subgroups. The most extensive study of this thesis, detailed in Chapter 6, showed that single laboratory-controlled 60-min exercise sessions increase both salivary secretory immunoglobulin A (sIgA), a marker of mucosal immunity, and α-amylase, a marker of sympathetic activation in all three disability subgroups. However, the impaired sympathetic nervous system in tetraplegic athletes seemed to influence the fine-tuning of their sIgA response when compared with paraplegic and non-spinal cord-injured athletes, resulting in a larger exercise-induced increase of sIgA secretion rate when compared to paraplegic and non-spinal cord-injured athletes. Based on these results, the study detailed in Chapter 7 investigated sIgA responses in tetraplegic athletes during wheelchair rugby court training. Despite their disability, these athletes showed responses thought to be governed by the sympathetic nervous system, such as reductions of saliva flow rate as a result of strenuous exercise. Similarly, the responses observed in Chapter 8 imply a comparable trend of chronic sIgA exercise responses in tetraplegic athletes as found in the able-bodied population, namely a decrease in sIgA secretion rate during periods of heavy training. These are the first studies in wheelchair athlete populations to investigate mucosal immune responses. Interestingly, despite the disruption of their sympathetic nervous system, some responses in tetraplegic athletes are comparable with findings in able-bodied populations. It is possible that due to their highly trained nature, these tetraplegic individuals are able to compensate for their loss of central sympathetic innervation. This may be by way of adapted spinal reflex or parasympathetic nervous system activity, or increased sensitivity of receptors involved in autonomic pathways. Therefore, sympathetic nervous function in tetraplegic athletes may be qualitatively altered, but in parts still be functional.