Glucose-fructose likely improves gastrointestinal comfort and endurance running performance relative to glucose-only.

This study aimed to determine whether glucose-fructose (GF) ingestion, relative to glucose-only, would alter performance, metabolism, gastrointestinal (GI) symptoms, and psychological affect during prolonged running. On two occasions, 20 runners (14 men) completed a 120-min submaximal run followed by a 4-mile time trial (TT). Participants consumed glucose-only (G) or GF (1.2:1 ratio) beverages, which supplied ∼ 1.3 g/min of carbohydrate. Substrate use, blood lactate, psychological affect [Feeling Scale (FS)], and GI distress were measured. Differences between conditions were assessed using magnitude-based inferential statistics. Participants completed the TT 1.9% (-1.9; -4.2, 0.4) faster with GF, representing a likely benefit. FS ratings were possibly higher and GI symptoms were possibly-to-likely lower with GF during the submaximal period and TT. Effect sizes for GI distress and FS ratings were relatively small (Cohen's d = ∼0.2 to 0.4). GF resulted in possibly higher fat oxidation during the submaximal period. No clear differences in lactate were observed. In conclusion, GF ingestion - compared with glucose-only - likely improves TT performance after 2 h of submaximal running, and GI distress and psychological affect are likely mechanisms. These results apply to runners consuming fluid at 500-600 mL/h and carbohydrate at 1.0-1.3 g/min during running at 60-70% VO2peak .

Of growing importance: combining greater early vigour and transpiration efficiency for wheat in variable rainfed environments.

Increasing climate variability, particularly variability in the timing and amount of soil water, means that breeding wheat (Triticum aestivum L.) varieties with stable high grain yields is increasingly more challenging. Changing environmental conditions in water-limited rainfed environments will alter genotype ranking to reduce confidence in the identification of consistently higher yielding performers. Greater early vigour (EV) and transpiration efficiency (TE) are two physiological traits that have demonstrated benefits as breeding targets for efficient water-use in Mediterranean in-season water and monsoonal stored water environments, respectively. This Perspective discusses the hypothesis that combining higher TE and greater EV will broaden the adaptation and increase grain yields for wheats grown across most rainfed environments. We examine the physiology underpinning adaptation with greater EV and higher TE, as well as the challenges and potential benefits of deploying these traits in combination. We then discuss how these two traits interact with different environments and, in particular, the different wheat-growing regions of Australia. We conclude that the combination of these two traits is genetically and physiologically feasible, as well theoretically beneficial to average yield in most rainfed environments. Hence, we suggest a strategy for reliably managing the complex genetics underpinning EV and TE when phenotyping and selecting both traits in commercial wheat breeding programs.

Moderate-to-vigorous physical activity in individuals with psoriasis: associations with body surface area and subjective disease severity.

AIM: Psoriasis is associated with serious comorbidities such as cardiovascular disease, type 2 diabetes, and metabolic syndrome. These comorbidities are related to low physical activity in the general population. Limited research has evaluated physical activity in psoriasis, and thus, the purpose of this investigation was to compare physical activity between individuals with and without psoriasis as well as explore the associations between measures of psoriasis severity and physical activity. METHODS: Cross-sectional study using data from the 2003-2006 National Health and Nutrition Examination Survey. Self-reported psoriasis diagnosis and psoriasis severity were regressed on moderate/vigorous physical activity, as measured objectively by accelerometers. Measures of psoriasis severity included rating of psoriasis as a problem in life and body surface area involvement. RESULTS: A total of 4316 individuals had data on psoriasis, moderate/vigorous physical activity, and relevant covariates, with 3.6% (population weighted) of participants (N.=117) reporting a diagnosis of psoriasis. A psoriasis diagnosis was not associated with moderate/vigorous physical activity, and furthermore, body surface area involvement was not associated with moderate/vigorous physical activity among participants with psoriasis. However, every tertile increase in psoriasis as a problem in life was associated with 28% less moderate/vigorous physical activity, which remained significant after adjusting for covariates and removing outliers. CONCLUSION: While a diagnosis of psoriasis and body surface area involvement do not appear to be associated with less moderate/vigorous physical activity, individuals that rate their psoriasis to be a large problem engage in less moderate/vigorous physical activity.

Psoriasis and physical activity: a review.

Psoriasis is a common, chronic inflammatory skin disease that can cause significant discomfort and impairment to quality of life. Recent research indicates that individuals with moderate-to-severe psoriasis are likely at greater risk for chronic cardiometabolic co-morbidities such as cardiovascular disease, type 2 diabetes, obesity and metabolic syndrome. Physical activity can be an effective primary and adjunctive treatment for these maladies in other populations. Unfortunately, only a limited number of studies have examined physical activity in psoriasis, which are limited by poor design and lack of validated physical activity assessment methodologies. A variety of data suggest shared physiologic pathways between physical activity, psoriasis, and psoriasis cardiometabolic co-morbidities. Increased adiposity, inflammation, oxidative stress, adhesion molecules and lipids are physiologically linked to psoriasis, the risk of psoriasis cardiometabolic co-morbidities, and low levels of physical activity. In addition, epigenetic pathways are involved in psoriasis and could be influenced by physical activity. The physical and psychosocial impairments common in psoriasis may make it difficult to participate in regular physical activity, and future studies should aim to determine if physical activity interventions improve functioning and reduce co-morbidities in psoriasis.

Elevated plasma CD105 and vitreous VEGF levels in diabetic retinopathy.

Diabetic retinopathy is the leading cause of blindness in the industrialized world. Hyperglycaemia induces retinal hypoxia that upregulates a range of vasoactive factors which may lead to macular oedema and/or angiogenesis and hence potentially sight threatening retinopathy. In this study, we have focused on the association of CD105 and vascular endothelial growth factor (VEGF) with the development and progression of diabetic retinopathy by means of quantifying their expression in the plasma and vitreous of diabetic patients. CD105 levels were quantified in the plasma of 38 type I diabetic patients at various stages of retinopathy and 15 non-diabetic controls. In an additional cohort of 11 patients with advanced proliferative retinopathy and 23 control subjects, CD105 and VEGF were measured in the vitreous. The values were expressed as median (range) and statistical analysis was carried out using the non-parametric Mann-Whitney U test. Plasma CD105 levels were significantly increased in diabetic patients [1.8 (1.1-2.4) ng/ml] compared with non-diabetic controls [0.7 (0.3-1.8) ng/ml] (p<0.01). Plasma CD105 levels were elevated in diabetic patients with all stages of retinopathy, the highest level was observed in background retinopathy [2.3 (2.1-2.5) ng/ml] followed by proliferative retinopathy [2.1 (0.9-2.8) ng/ml] and advanced proliferative retinopathy [1.4 (0.6-1.8) ng/ml]. Vitreous contents of CD105 did not differ between controls and patients with advanced proliferative retinopathy, but vitreous levels of VEGF were elevated by approximately 3-fold in patients with advanced proliferative retinopathy [7.2 (1.90-15.60) ng/ml] compared with the control subjects [1.80 (1.10-2.210)] (p<0.01). These observations indicate that plasma levels of CD105 and vitreous levels of VEGF are associated with diabetic retinopathy, suggesting that CD105 and the angiogenic factor VEGF may play a critical role in the development and progression of diabetic retinopathy. Further studies are required to determine whether circulating CD105 levels could serve as a surrogate marker for early stage retinopathy and for monitoring disease progression.

The significance of CD105, TGFbeta and CD105/TGFbeta complexes in coronary artery disease.

We have quantified levels of CD105, its ligand TGFbeta and receptor-ligand complexes in sera from healthy individuals (n=31), patients with triple vessel disease documented by coronary angiography (TVD; n=36) and patients with chest pain and a positive exercise electrocardiogram but with normal coronary angiogram (NCA; n=30). Both active TGFbeta1 and active plus acid-activatable TGFbeta1 [(a+l)TGFbeta1] were significantly depressed in patients with TVD compared with the other two groups (P

Plasma levels of soluble CD105 correlate with metastasis in patients with breast cancer.

CD105 (endoglin), a receptor for transforming growth factor (TGF) beta1 and beta3 in vascular endothelial cells, is highly up-regulated in blood vessels of tissues where neovascularisation occurs. It modulates endothelial-mesenchymal signalling and is essential for angiogenesis. Indeed, CD105 knock-out mice die from malvascularisation by 11.5 day p.c. In the present study CD105, TGFbeta1 and CD105/TGFbeta1 complexes were quantified in plasma samples from 77 healthy individuals and 92 patients with early stage breast cancer prior to any treatment. When compared with normal controls, both CD105 and CD105/TGFbeta1 complex levels were significantly elevated in breast cancer patients, whereas TGFbeta1 levels were lower in cancer patients. The most important finding to emerge was that CD105 levels were significantly increased in patients who developed distant metastasis compared with disease-free patients. While there was no significant difference between CD105 levels in controls compared to disease-free patients, it was significantly higher in patients with metastatic disease. Thus patients who had died following local relapse or distant metastases possessed the highest levels of CD105. Neither CD105/TGFbeta1 complex nor TGFbeta1 levels correlated with tumour progression. Our data indicate that CD105 might be a valuable novel angiogenic marker for identifying breast cancer patients who are at high risk of developing metastasis.

Specific immunoglobulin E to peanut, hazelnut and brazil nut in 731 patients: similar patterns found at all ages.

BACKGROUND: Previous studies have reported reactions to an increasing range of nuts as patients with nut allergy grow older. Most patients with symptoms suggesting nut allergy have specific IgE to more than one nut. Furthermore, fatal reactions have followed eating nuts different from any causing the deceased's previous reactions. OBJECTIVE: To explore the pattern of specific IgE to three distantly related nuts in patients of all ages with nut allergy. METHODS: This study includes all patients referred to our laboratory for nut allergy testing from January 1994 to August 1998 who were tested for peanut, hazelnut and brazil nut, and had specific IgE to at least one of these nuts. All tests were performed using the Pharmacia Unicap system. RESULTS: Seven hundred and thirty-one patients (age 7 months to 65 years, median 6.6 years) had specific IgE >0.35 kU(A)/L to at least one of these three nuts: 282 had IgE to one nut, 130 to two nuts, and 319 to all three nuts. When analysed by gender and age quartile, very similar patterns were found in all subgroups though significant age trends and age interactions were found for IgE to individual nuts and combinations of nuts. CONCLUSIONS: The probability of a patient with nut allergy having specific IgE to a particular combination of peanut, hazelnut and brazil nut is similar, whatever their age or sex. The apparent increase in multiple nut reactivity with increasing age may therefore be due to exposure of previously unchallenged sensitivity. The frequency of multiple-nut specificity is sufficiently high that patients should always be tested for allergy to a range on nuts if they have a history of reacting to any nut.

TGF-beta1 levels in pre-treatment plasma identify breast cancer patients at risk of developing post-radiotherapy fibrosis.

A serious complication of radiotherapy in the treatment of cancer patients is the late onset of fibrosis in normal tissues. Transforming growth factor beta (TGF-beta) is emerging as a key mediator of the fibrotic process through its effects on stimulation of fibroblast proliferation, migration and extracellular matrix (ECM) synthesis. The fact that radiation-induced vascular injury tends to precede the development of fibrosis has led to the suggestion that vascular damage is crucial in its pathogenesis. CD105, the specific type III vascular receptor for TGF-beta1 and -beta3, modulates cell proliferation and ECM production in response to TGF-beta in vitro. In this study, we have quantified the levels of TGF-beta1 and soluble CD105-TGF-beta1 complex in 91 pre-radiotherapy plasma samples from early-stage (T1 or T2) breast cancer patients utilising an enhanced chemiluminescence ELISA system. During the follow-up period, 24 patients had developed moderate and one severe fibrosis of the breast. The mean TGF-beta1 level in these 25 patients was 203.2 +/- 37.3 pg/ml, which was significantly elevated above the level for those with no fibrosis. Furthermore, a significantly lower CD105-TGF-beta1 complex level was observed in the former compared to the latter. Spearman's correlation analysis showed that TGF-beta1 was positively correlated and the CD1O5-TGF-beta1 complex inversely correlated with the occurrence of breast fibrosis. Using a cut-off value of 96 pg/ml, the sensitivity and specificity of TGF-beta1 levels in predicting breast fibrosis were 76% and 74%, respectively. Our results indicate that TGF-beta1 and the receptor-ligand complex appear to be of clinical value in identifying patients at risk of developing post-radiotherapy fibrosis.

Immunodetection and characterisation of soluble CD105-TGFbeta complexes.

CD105 (endoglin) is a receptor for transforming growth factor beta (TGFbeta). Although methods to measure soluble forms of TGFbeta and CD105 have been published, no assay is available to quantify the receptor-ligand complexes. We describe both an indirect enzyme-linked immunosorbent assay for the quantitation of soluble CD105-TGFbeta1 and the characterization of the complexes by immunoprecipitation and immunoblotting. Mab E9, specifically reactive with CD105, was utilised as the capture reagent in the ELISA system. Detection of complexes was achieved using chicken antibody against TGFbeta1 and the subsequent detection of bound antibody demonstrated by the addition of anti-species antiserum conjugated to horseradish peroxidase (HRP). By using enhanced chemiluminescence and optimised antibodies, the assay was made sufficiently sensitive and reproducible to detect low levels of circulating complexes. Whether the assay had any practical applications was evaluated in breast cancer patients. Plasma levels of CD105-TGFbeta1 were significantly elevated in 59 patients with breast cancer compared to 52 age matched normal women (p < 0.001). Immunoprecipitation using a rabbit anti-CD105 antibody, which reacts with both dimeric and monomeric CD105, and immunoblotting showed that three molecular forms of CD105-TGFbeta1 complexes > 200, 195, and 125 kDa existed in the plasma. We believe these represent the oligomer, dimer and probably the protease degraded form of CD105 complexed to TGFbeta1. The resistance to hypertonic solution, SDS and heat treatment suggested that the soluble CD105-TGFbeta1 complex may be linked by covalent bonds. The measurement of CD105-TGFbeta complexes in the circulation may have important clinical applications not only in cancer but also in patients with other angiogenic diseases such as rheumatoid arthritis, myocardial infarction and stroke.

Role of transforming growth factor beta3 in lymphatic metastasis in breast cancer.

Transforming growth factor-betas (TGFbetas) play a prominent role in tumour growth and metastasis by enhancing angiogenesis and suppressing immune surveillance. Despite the increased interest in the effect of TGFbetas on tumour progression, little is known about the importance of TGFbeta3 and its receptor CD105 in breast cancer. In the present study, we measured the plasma levels of TGFbeta3, CD105-TGFbeta3 complexes and TGFbeta1 in 80 patients with untreated early-stage breast cancer using an enhanced chemiluminescence ELISA method. Of the 80 patients, 14 were histologically confirmed as having axillary lymph node metastases, while the remainder had no evidence of lymph node involvement. The results showed that levels of both TGFbeta3 and CD105-TGFbeta3 complex were significantly elevated in patients with positive lymph nodes compared to those without node metastasis. Furthermore, the levels of both TGFbeta3 and CD105-TGFbeta3 complex correlated with lymph node status. The only patient who died of the disease had very high plasma levels of TGFbeta3 and CD105-TGFbeta3 complex and positive lymph nodes; this patient developed lung metastases within 2 years of diagnosis. No significant correlation was seen between either TGFbeta3 or CD105-TGFbeta3 complex levels and tumour stage, size or histological grade. Plasma TGFbeta1 levels were not correlated with node metastasis, tumour stage, grade or size. Our data suggest that plasma levels of TGFbeta3 and CD105-TGFbeta3 complex may be of prognostic value in the early detection of metastasis of breast cancer.

Serum sCD23 in patients with lepromatous and tuberculoid leprosy.

Tuberculoid and lepromatous leprosy (TL and LL) manifest exaggerated Th1 and Th2 type immunity, respectively. Serum soluble CD23, which is regulated by the stimulatory action of IL4 and inhibitory action of IFNgamma, was significantly elevated in LL relative to TL and healthy controls. These results confirm the state of cellular and humoral immunity in TL and LL.

Serum levels of the TGF-beta receptor are increased in atherosclerosis.

Murine monoclonal antibody E9 recognises a transforming growth factor (TGF) beta receptor, which is expressed in increased amounts by activated endothelial cells. In order to examine the biological role of this molecule in atherosclerosis, we have measured levels of the TGF-beta receptor alongside those of two other endothelial cell products (von Willebrand factor and soluble E-selectin) in the serum of 55 patients with atherosclerosis (29 with ischaemic heart disease and 26 with peripheral vascular disease), and in a cohort of 26 age- and sex-matched asymptomatic controls. There were increased levels of the TGF-beta receptor (P = 0.0079) and von Willebrand factor (P = 0.0001), but not soluble E-selection in patients' serum relative to the controls. In multivariate analysis of the endothelial cell products against total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressures, age, sex and smoking, both the TGF-beta receptor and von Willebrand factor correlated with total cholesterol (Spearman's r = 0.37 and r = 0.35, respectively, both P < 0.001). Lack of a correlation with a coarse endothelial damage marker von Willebrand factor or soluble E-selectin (produced by immunologically stimulated endothelial cells) implies other mechanisms are responsible for increased levels of the TGF-beta receptor in serum of patients with atherosclerosis.

Serum soluble CD23 in patients with hypogammaglobulinaemia.

Serum levels of the soluble form of the low-affinity receptor for IgE (FcERII, CD23) (sCD23) are elevated in autoimmune conditions associated with hypergammaglobulinaemia and B cell hyperactivity. Very high levels of sCD23 are found in patients with B-chronic lymphatic leukaemia (B-CLL) who are, however, frequently hypogammaglobulinaemic. We therefore compared the serum levels of sCD23 in healthy controls (n = 33) with three conditions associated with hypogammaglobulinaemia (HGG) and varying B cell numbers: X-linked agammaglobulinaemia (XLA, n = 12), common variable immunodeficiency (CVI, n = 20) and B-chronic lymphatic leukaemia (n = 33). Serum levels of sCD23 showed a significant correlation with the CD19+ B cell count in both normals and patients with CVI (r = 0.65, P < 0.0001). Amongst the different clinical groups, serum levels of sCD23 were increased in the order XLA < CVI < normals < CLL (medians 2.5, 7.7, 11.1 and 540, respectively; P < 0.001 for all comparisons except CVI versus normals P < 0.03 in a one-tailed test). In the CVI group, serum sCD23 was lowest amongst four patients with low B cell numbers. There was no overlap in sCD23 between patients with XLA and this subgroup of CVI patients. Serum sCD23 is, therefore, derived predominantly from B cells, and is significantly related to the peripheral blood B cell count.

Quantitation of endothelial cell specific protein E-9 employing a single monoclonal antibody in an indirect sandwich ELISA.

An indirect enzyme-linked immunosorbent assay is described for the quantitation of protein E-9 which is specifically expressed on human vascular endothelial cells. The assay capitalizes on the dimeric structure of the E-9 protein by utilizing a single monoclonal antibody as both the capture and detection reagent. Detection is achieved by conjugating the Mab with biotin and is followed by the addition of streptavidin peroxidase to provide high sensitivity. Bound activity is measured by enhanced chemiluminescence utilizing standard Amerlite chemistry. The optimised assay is reproducible and is highly sensitive. Using this assay it was possible to detect the presence of E-9 protein in tissue culture media of endothelial cells and in serum samples--in one case even at 1/100 dilution. In vitro, X irradiation resulted in a greater than two-fold increase (P < or = 0.005) in the level of E-9 protein in culture supernatants of human umbilical vein endothelial cells (HUVEC). There are potential applications for measurements of E-9 protein in body fluids and tissue extracts from patients with a vast variety of diseases characterised by vascular endothelial damage and/or activation.

Increased levels of sCD23 in rheumatoid arthritis are related to disease status.

The low affinity receptor for IgE (Fc epsilon RII, CD23) is involved in many aspects of T and B cell regulation. In the current study, serum levels of sCD23 were measured in monozygotic (MZ) twins discordant for rheumatoid arthritis (RA) to examine whether an increased level of sCD23 in RA is, at least in part, genetically determined. Paired analysis showed significantly elevated sCD23 levels in affected twins when compared with their unaffected co-twins (p < 0.01). There was no significant difference in sCD23 in the unaffected twins compared with normal controls. Higher levels of sCD23 were found in males compared to females in both affected and unaffected twins. Soluble CD23 showed a significant increase with age in RA affected twins (p = 0.013), but no association with disease duration (p = 0.87). There was no significant variation in sCD23 level with HLA-DR phenotype. We conclude that elevations in serum sCD23 in patients with RA are primarily disease related.

IgM ganglioside GM1 antibodies in patients with autoimmune disease or neuropathy, and controls.

AIMS: To compare the titre of anti-ganglioside antibodies (AGA) to GM1 ganglioside in patients with central and peripheral neurological disease and pure motor and sensorimotor neuropathy, in patients with classic autoimmune diseases, and controls. METHODS: AGA to GM1 were measured using an enzyme linked immunosorbent assay (ELISA) technique, highly purified bovine GM1 ganglioside, and sequential dilution of control and test sera. Antibody titre was calculated using the optical density readings of three consecutive serum dilutions multiplied by the dilution factor. RESULTS: A considerable overlap was evident in the titre of AGA to GM1 in control and test sera. High antibody titres were most frequent in patients with multifocal motor neuropathy with conduction block (MMNCB). Low AGA titre were observed in several patient groups. Compared with the controls, the median titre of AGA to GM1 was significantly higher in patients with multiple sclerosis, rheumatoid arthritis, primary Sjögren's syndrome and systemic lupus erythematosus. In contrast, the median titre in patients with diabetic peripheral neuropathy, motor neurone disease, sensorimotor neuropathy and chronic inflammatory demyelinating polyneuropathy was no different from that in normal control subjects. CONCLUSIONS: Estimation of AGA to GM1 may be helpful in the diagnosis of MMNCB in patients with a pure motor neuropathy but in few other conditions. Low titre AGA to GM1 are evident in several autoimmune conditions. The pathogenetic importance of AGA to GM1 in patients with neuropathy is not clear.

Serum measurements of soluble CD23 in HIV infection.

A gradual reduction in cell-mediated immunity is thought to occur with the progression of human immunodeficiency virus (HIV) infection. This suggests a selective attrition of the Th1 subset. The regulation of the soluble form of the low-affinity receptor for IgE (sCD23) by the opposing actions of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) allows the assessment of the overall balance of Th1 to Th2 activity in a given disease. In order to investigate this further we employed an enhanced chemiluminescent ELISA to analyse serum levels of sCD23 in male subjects with and without HIV infection. Serum levels of sCD23 were similar in 34 HIV seronegative homosexuals, 39 homosexuals with asymptomatic HIV infection, 27 homosexuals with acquired immune deficiency syndrome (AIDS) and 20 healthy controls. This suggests that HIV has no predilection for either the Th1 or Th2 subsets of CD4 T cells.