Effects of 24-week prebiotic intervention on self-reported upper respiratory symptoms, gastrointestinal symptoms, and markers of immunity in elite rugby union players.

OBJECTIVES: Elite rugby union players face numerous physiological and psychological stressors which can increase upper respiratory and gastrointestinal illness risk, and in turn can compromise training and competitive performance. This study aimed to investigate the effect of daily prebiotic supplementation on upper respiratory symptoms, gastrointestinal symptoms, and markers of immune function in elite rugby union players. METHODS: Thirty-three elite rugby union players were randomly assigned to consume a prebiotic (2.8 g/day galactooligosaccharide) or placebo (2.8 g/day maltodextrin), daily for 168 days under double-blind conditions. Participants completed daily and weekly questionnaires for self-reported upper respiratory and gastrointestinal symptoms respectively. Blood and saliva samples were collected at 0, 84, and 168 days for assessment of plasma TNF-α and CRP, and saliva IgA respectively. RESULTS: The prebiotic group experienced a 2-day reduction in upper respiratory symptom duration (P = 0.045). Gastrointestinal symptom severity and incidence were lower in the prebiotic group compared to the placebo group (P < 0.001, P = 0.041) respectively. Salivary immunoglobulin A secretion rate was 42% greater in the prebiotic group compared to the placebo group at day 168 (P = 0.004), no differences in CRP and TNF-α were found (P > 0.05). CONCLUSION: A 168-day dietary prebiotic intervention reduced the duration of upper respiratory symptoms and reduced the incidence and severity of gastrointestinal symptoms in elite rugby union players. These findings suggest that seasonal prebiotic interventions may be beneficial for reducing illness in elite rugby union players, improving their availability to train and compete.Key pointsElite athletes are susceptible to upper respiratory symptoms and gastrointestinal symptoms which may impact upon training availability and competition performance.For the first time, this study shows that a dietary prebiotic intervention can reduce the duration of upper respiratory symptoms by 2 days in elite rugby union players.Dietary prebiotic supplementation can improve the incidence and severity of gastrointestinal symptoms experienced by elite rugby union players.Prebiotic supplementation was able to increase salivary IgA secretion after 168 days.These findings can inform practice suggesting that seasonal prebiotic use has the potential to modulate immune function and reduce illness in elite rugby union, which may improve a player's availability to train and compete.The mechanisms by which prebiotics reduce URS and GIS require further research exploration.

The effect of trait self-control on dyspnoea and tolerance to a CO2 rebreathing challenge in healthy males and females.

BACKGROUND: High trait self-control is associated with greater tolerance of unpleasant sensations including effort and pain. Dyspnoea and pain have several commonalities and this study aimed to investigate for the first time whether trait self-control influences responses to a hypercapnic rebreathing challenge designed to induce dyspnoea. As sex also influences tolerance to dyspnoea, we also sought to investigate whether this moderated the role of trait self-control. METHODS: Participants (n = 65, 32 females) scoring high or low for trait self-control, performed a standardised rebreathing challenge, in which inspired carbon dioxide (CO2) gradually increased over a period of 6 min or until an intolerable level of dyspnoea. Air hunger (AH) intensity - a distinctive quality of dyspnoea, was measured every 30 s. The multidimensional dyspnoea profile (MDP) was completed after the rebreathing challenge for a more complete overview of breathing discomfort. RESULTS: Males high in trait self-control (SCHIGH) (302 ± 42 s), tolerated the rebreathing challenge for longer than males low in self-control (SCLOW) (252 ± 66 s, P = 0.021), experienced slower increases in AH intensity during the rebreathing challenge (0.03 ± 0.01 cm.s - 1 vs. 0.04 ± 0.01 cm.s - 1,P = 0.045) and reported lower perceived mental effort on the MDP (4.94 ± 2.46 vs. 7.06 ± 1.60, P = 0.007). There was no difference between SCHIGH and SCLOW females for challenge duration. However, SCHIGH females (9.29 ± 0.66 cm) reported greater air hunger at the end of the challenge than SCLOW females (7.75 ± 1.75 cm, P = 0.003). It is possible that SCLOW females were unwilling to tolerate the same perceptual intensity of AH as the SCHIGH females. CONCLUSIONS: These results indicate that individuals high in trait self-control are more tolerant of dyspnoea during a CO2 rebreathing challenge than low self-control individuals. Tolerance of the stimulus was moderated by the sex of the participant, presenting an interesting opportunity for future research.

Reproducibility of the bronchoconstrictive response to eucapnic voluntary hyperpnoea.

BACKGROUND: Eucapnic voluntary hyperpnoea (EVH) is considered an effective bronchoprovocation challenge for identifying exercise-induced bronchoconstriction (EIB). However, the reproducibility of the hyperpnoea-induced bronchoconstriction (HIB) response elicited by EVH remains unknown and was therefore the focus of this study. METHODS: Two cohorts of 16 physically active males (each cohort comprised 8 controls and 8 with physician diagnosis of asthma) participated in two studies of the short- and long-term reproducibility of the bronchoconstrictive response to an EVH test with dry air. EVH was performed on days 0, 7, 14, and 21 (short-term study), and 0, 35, and 70 (long-term study). HIB was diagnosed by a ≥10% fall in forced expiratory volume in 1 s (FEV1) after EVH. RESULTS: On day 0 of the short-term study, FEV1 fell by 2 ± 1% (P < 0.05) and 27 ± 18% (P < 0.01) from pre-to post-EVH in control and HIB-positive groups respectively. The post-EVH fall in FEV1 did not differ across the short-term study test days. In the HIB-positive group, the day-to-day coefficient of variation, reproducibility, and smallest meaningful change for the fall in FEV1 were 12%, 328 mL, and 164 mL, respectively. On day 0 of the long-term study, FEV1 fell by 2 ± 2% and 25 ± 18% (P < 0.01) after EVH in control and HIB-positive groups respectively. The post-EVH fall in FEV1 did not differ across the long-term study test days. In the HIB-positive group, the day-to-day coefficient of variation, reproducibility, and smallest meaningful change for the fall in FEV1 were 10%, 196 mL, and 98 mL respectively. CONCLUSION: The EVH test elicits a reproducible bronchoconstrictive response in physically active males with physician diagnosed asthma. These data thus support the clinical utility of the EVH test for EIB screening and monitoring.

Locomotor muscle fatigue is not critically regulated after prior upper body exercise.

This study examined the effects of prior upper body exercise on subsequent high-intensity cycling exercise tolerance and associated changes in neuromuscular function and perceptual responses. Eight men performed three fixed work-rate (85% peak power) cycling tests: 1) to the limit of tolerance (CYC); 2) to the limit of tolerance after prior high-intensity arm-cranking exercise (ARM-CYC); and 3) without prior exercise and for an equal duration as ARM-CYC (ISOTIME). Peripheral fatigue was assessed via changes in potentiated quadriceps twitch force during supramaximal electrical femoral nerve stimulation. Voluntary activation was assessed using twitch interpolation during maximal voluntary contractions. Cycling time during ARM-CYC and ISOTIME (4.33 ± 1.10 min) was 38% shorter than during CYC (7.46 ± 2.79 min) (P < 0.001). Twitch force decreased more after CYC (-38 ± 13%) than ARM-CYC (-26 ± 10%) (P = 0.004) and ISOTIME (-24 ± 10%) (P = 0.003). Voluntary activation was 94 ± 5% at rest and decreased after CYC (89 ± 9%, P = 0.012) and ARM-CYC (91 ± 8%, P = 0.047). Rating of perceived exertion for limb discomfort increased more quickly during cycling in ARM-CYC [1.83 ± 0.46 arbitrary units (AU)/min] than CYC (1.10 ± 0.38 AU/min, P = 0.003) and ISOTIME (1.05 ± 0.43 AU/min, P = 0.002), and this was correlated with the reduced cycling time in ARM-CYC (r = -0.72, P = 0.045). In conclusion, cycling exercise tolerance after prior upper body exercise is potentially mediated by central fatigue and intolerable levels of sensory perception rather than a critical peripheral fatigue limit.

Inspiratory muscle warm-up does not improve cycling time-trial performance.

PURPOSE: This study examined the effects of an active cycling warm-up, with and without the addition of an inspiratory muscle warm-up (IMW), on 10-km cycling time-trial performance. METHODS: Ten cyclists (VO2 = 65 ± 9 mL kg(-1) min(-1)) performed a habituation 10-km cycling time-trial and three further time-trials preceded by either no warm-up (CONT), a cycling-specific warm-up (CYC) comprising three consecutive 5-min bouts at powers corresponding to 70, 80, and 90% of the gas exchange threshold, or a cycling-specific warm-up preceded by an IMW (CYC + IMW) comprising two sets of 30 inspiratory efforts against a pressure-threshold load of 40% maximal inspiratory pressure (MIP). The cycling warm-up was followed by 2-min rest before the start of the time-trial. RESULTS: Time-trial performance times during CYC (14.75 ± 0.79 min) and CYC + IMW (14.70 ± 0.75 min) were not different, although both were faster than CONT (14.99 ± 0.90 min) (P < 0.05). Throughout the time-trial, physiological (minute ventilation, breathing pattern, pulmonary gas exchange, heart rate, blood lactate concentration and pH) and perceptual (limb discomfort and dyspnoea) responses were not different between CYC and CYC + IMW. Baseline MIP during CONT and CYC was 151 ± 31 and 156 ± 39 cmH2O, respectively, and was unchanged following the time-trial. MIP increased by 8% after IMW (152 ± 27 vs. 164 ± 27 cmH2O, P < 0.05) and returned to baseline after the time-trial. CONCLUSIONS: Improvements in 10-km cycling time-trial performance following an active cycling warm-up were not magnified by the addition of an IMW. Therefore, an appropriately designed active whole-body warm-up does adequately prepare the inspiratory muscles for cycling time-trials lasting approximately 15 min.

Effects of protocol design on lactate minimum power.

The aim of this investigation was to use a validated lactate minimum test protocol and evaluate whether blood lactate responses and the lactate minimum power are influenced by the starting power (study 1) and 1 min inter-stage rest intervals (study 2) during the incremental phase. Study 1: 8 subjects performed a lactate minimum test comprising a lactate elevation phase, recovery phase, and incremental phase comprising 5 continuous 4 min stages with starting power being 40% or 45% of the maximum power achieved during the lactate elevation phase, and with power increments of 5% maximum power. Study 2: 8 subjects performed 2 identical lactate minimum tests except that during one of the tests the incremental phase included 1 min inter-stage rest intervals. The lactate minimum power was lower when the incremental phase commenced at 40% (175±29 W) compared to 45% (184±30 W) maximum power (p<0.01), and was increased when 1 min inter-stage rest intervals were included during the incremental phase (192±25 vs. 200±26 W, p<0.01). In conclusion, changes in lactate minimum power were small and thus unlikely to compromise test validity and therefore training status evaluation and exercise prescription.

Investigations of the lactate minimum test.

We evaluated: the agreement between lactate minimum and maximal lactate steady state (MLSS) cycling powers (study 1); whether rates of change of blood lactate concentration during the lactate minimum test reflect that of constant power exercise (study 2); whether the lactate minimum power is influenced by the muscle groups used to elevate blood lactate concentration (study 3). Study 1: 32 subjects performed a lactate minimum test comprising a lactate elevation phase, recovery phase, and incremental phase (five 4 min stages); MLSS was subsequently determined. Study 2: 8 subjects performed a lactate minimum test and five 22 min constant power tests at the incremental phase exercise intensities. Study 3: 10 subjects performed two identical lactate minimum tests, except during the second test the lactate elevation phase comprised arm-cranking. Lactate minimum and MLSS powers demonstrated good agreement (mean bias+/-95% limits of agreement: 2+/-22 W). Rates of change of blood lactate concentration during each incremental phase stage and corresponding constant power test did not correlate. Lactate minimum power was lowered when arm-cranking was used during the lactate elevation phase (157+/-29 vs. 168+/-21 W; p<0.05). The lactate elevation phase modifies blood lactate concentration responses during the incremental phase, thus good agreement between lactate minimum and MLSS powers seems fortuitous.

Inflammatory mediators in normal, sensitive and diseased skin types.

The role of inflammatory mediators in the pathogenesis and pathophysiology of skin diseases is now widely accepted. We analysed the profiles of inflammatory mediators in normal, sensitive (past history of eczema, but currently patch test negative) and diseased (psoriasis and eczema) skin types to identify the patterns associated with various degrees of inflammatory dermatoses. Compared with normal skin, prostaglandin E2 was increased approximately 3.8-fold (p<0.0002) and 4.7-fold (p<0.0001) in suction blister fluids from sensitive and diseased skin types, respectively. Leukotriene B4 and interleukin-1alpha showed no differences between normal and sensitive skin types. However, in lesional skin from psoriasis and eczema patients, leukotriene B4 was increased approximately 6.6-fold (p<0.0001), whereas interleukin-1alpha was decreased approximately 3.1-fold (p<0.001). Interleukin 6 and tumour necrosis factor-alpha could not discriminate between skin types. We conclude that only prostaglandin E2 showed a significant stepwise increase on progression from normal through sensitive and inflammatory skin diseases. Levels of leukotriene B4 and interleukin-1alpha were also indicative of disease state and may be important in the pathophysiology of these conditions.

Regulation of epidermal homeostasis through P2Y2 receptors.

1. Previous studies have indicated a role for extracellular ATP in the regulation of epidermal homeostasis. Here we have investigated the expression of P2Y2 receptors by human keratinocytes, the cells which comprise the epidermis. 2. Reverse transcriptase-polymerase chain reaction (RT - PCR) revealed expression of mRNA for the G-protein-coupled, P2Y2 receptor in primary cultured human keratinocytes. 3. In situ hybridization studies of skin sections revealed that P2Y2 receptor transcripts were expressed in the native tissue. These studies demonstrated a striking pattern of localization of P2Y2 receptor transcripts to the basal layer of the epidermis, the site of cell proliferation. 4. Increases in intracellular free Ca2+ concentration ([Ca2+]i) in keratinocytes stimulated with ATP or UTP demonstrated the presence of functional P2Y receptors. 5. In proliferation studies based on the incorporation of bromodeoxyuridine (BrdU), ATP, UTP and ATPgammaS were found to stimulate the proliferation of keratinocytes. 6. Using a real-time firefly luciferase and luciferin assay we have shown that under static conditions cultured human keratinocytes release ATP. 7. These findings indicate that P2Y2 receptors play a major role in epidermal homeostasis, and may provide novel targets for therapy of proliferative disorders of the epidermis, including psoriasis.

The antiproliferative effect of lectin from the edible mushroom (Agaricus bisporus) on human keratinocytes: preliminary studies on its use in psoriasis.

Lectins or agglutinins are proteins with affinity for specific sugar residues. Peanut agglutinin (PNA) and the lectin from the edible mushroom (Agaricus bisporus, ABL) both bind to the disaccharide galactosyl beta-1,3-N-acetyl galactosamine alpha-. This is expressed in keratinocytes as an O-linked chain on CD44, a polymorphic membrane glycoprotein. Many lectins are mitogens and PNA is a mitogen for colonic epithelial cells. However, ABL reversibly inhibits proliferation of colonic cancer cell lines without cytotoxicity and thus has therapeutic potential in situations such as psoriasis where proliferation is increased. We have therefore investigated the effect of ABL on the growth of normal human cultured keratinocytes and a human papilloma virus (HPV)-transformed cell line. In a 5-day dose-response study, keratinocyte growth was greatly reduced by 1.0 microg/mL ABL and completely inhibited by 3.0 microg/mL ABL (ANOVA, P < 0.0001). Exposure to 1.0 microg/mL ABL for only 8 h gave the same growth inhibition as did continued exposure for 3 days. No cytotoxic or morphological changes were observed. An HPV-immortalized cell line was relatively resistant to ABL: in a 5-day dose-response study, exposure to 30 microg/mL was required to inhibit cell growth completely. Topical application of ABL 0.01% or 0.1% to normal human skin caused no change in skin erythema, blood flow or thickness compared with vehicle or baseline (n = 6). ABL 0. 1% in white soft paraffin was compared with vehicle in 11 psoriatic patients, using comparative contralateral plaques. Twice daily application for 2 weeks showed no significant difference from vehicle-treated sites, although the skin thickness of plaques fell from 5.3 +/- 0.4 (n = 11, mean +/- SEM) to 4.1 +/- 0.3 mm. In view of the in vitro results further studies are warranted, particularly if means can be found to improve the epidermal penetration of the relatively large ABL molecule (60 kDa).

Seborrhoeic dermatitis is not caused by an altered immune response to Malassezia yeast.

The immune response of patients with seborrhoeic dermatitis and healthy age- and sex-matched controls was examined to test the hypothesis that an inadequate or inappropriate immune response to Malassezia yeast leads to seborrhoeic dermatitis. Antibody responses were examined using enzyme-linked immunosorbent assays (ELISAs) and Western blots and lymphocyte responses using lymphocyte proliferation assays. The level of IgG and IgM specific for whole yeast cells or extracted proteins of two isolates of M. furfur was tested in ELISA. A wide range of antibody levels was found but the patient and control groups were indistinguishable (n = 19), and the groups could not be distinguished by the pattern of Malassezia proteins recognized by their sera in Western blots. The average affinity of the subjects' antibodies specific for Malassezia cells or proteins was measured using ammonium thiocyanate dissociation. Most of the sera had moderate affinities corresponding to 50% dissociation at thiocyanate concentrations of 0.5-1.0 mol/L. There was no difference between patients and matched controls. The proliferation of the patients' lymphocytes in response to a number of M. furfur cell preparations was measured: whole cells, cytoplasmic proteins, cell walls, soluble molecules extracted from the cell walls using sonication, and a commercial preparation. There was a wide range of responses between individuals, but there was no difference between the three groups: patients with seborrhoeic dermatitis (n = 16), healthy controls (n = 16) and a group suffering from other inflammatory skin conditions (n = 15). The results do not support the hypothesis that an inadequate immune response to Malassezia yeast could lead to seborrhoeic dermatitis. Other possible pathological mechanisms include toxin production or lipase activity.

Human keratinocytes express transcripts for three isoforms of parathyroid hormone-related protein (PTHrP), but not for the parathyroid hormone/PTHrP receptor: effects of 1,25(OH)2 vitamin D3.

Parathyroid hormone-related protein (PTHrP) is strongly expressed in the epidermis and has been implicated in the regulation of growth and differentiation of keratinocytes. PTHrP has N-terminal sequence homology with parathyroid hormone (PTH) and binds to the type I PTH/PTHrP receptor, but earlier reports suggest that keratinocytes do not possess this cell surface receptor. In order to determine which PTHrP mRNA isoforms are expressed by keratinocytes and whether the type I receptor mRNA is present, we designed specific primers for reverse transcriptase-polymerase chain reaction. The interaction of PTHrP with other promoters of keratinocyte differentiation is unclear. In particular, 1,25(OH)2D3 is also fundamental in calcium homeostasis and induces changes in intracellular calcium. We therefore investigated the effect of 1,25(OH)2D3 on PTHrP mRNA expression and protein production in cultured human keratinocytes. Cells were incubated for 3 days at concentrations of 1.25(OH)2D3 of 10(-10)-10(-6) mol/L. PTHrP in culture supernatant, measured by two site immunoradiometric assay, was 915 +/- 98 PTHrP fmol/mg of cell layer protein in untreated cultures decreasing to 570 +/- 113 with 10(-8) mol/L and 402 +/- 24 with 10(-6) mol/L 1,25(OH)2D3 (mean +/- SEM, P < 0.01, n = 6). Transcripts for all three PTHrP isoforms (139, 141 and 173 amino acids) were detectable in keratinocyte mRNA. Corresponding to the decrease in PTHrP protein we demonstrated a reduction in all three PTHrP mRNA transcripts after 3 days' incubation with 1,25(OH)2D3 over a concentration range 10(-10)-10(-6) mol/L. Repeated studies failed to detect type I PTH/PTHrP receptor mRNA in human keratinocytes, either in control cultures or in the presence of 1,25(OH)2D3. We have shown that keratinocytes produce abundant PTHrP and that this is modulated by 1,25(OH)2D3, suggesting a physiological role. Further studies are required to investigate the relative expression of PTHrP isoforms, their role in keratinocyte signalling and the receptors involved.

Kaposi's sarcoma associated with immunosuppression for bullous pemphigoid.

Kaposi's sarcoma may occur in transplant recipients on immunosuppressive regimens, but is not well recognized in association with treatment for dermatological disease. We report two cases where multifocal Kaposi's sarcoma developed following iatrogenic immunosuppression with prednisolone and azathioprine for bullous pemphigoid. Both patients were HIV negative and, in one case, lesions regressed both clinically and histologically when immunosuppressive therapy was withdrawn.