Andrea J. Braakhuis

Innate and Adaptive Immune Responses to Nonvascular Xenografts: Evidence That Macrophages Are Direct Effectors of Xenograft Rejection

Nonvascularized xenograft rejection is T cell mediated, but is dependent on initial macrophage (Mφ) infiltration. We developed an i.p. transplant model to define the roles of Mφ and T cells in xenograft rejection. Nonobese diabetic or BALB/c mice were injected i.p. with xenogeneic, allogeneic, or syngeneic cells, and the responding cells in subsequent lavages were assessed by flow cytometry and adoptive transfer. Neutrophils and monocytes/elicited Mφ were rapidly recruited in response to xenogeneic pig (PK15 or spleen) cells and, to a significantly lesser extent, allogeneic cells. These innate responses preceded T cell infiltration and occurred in their absence in SCID mice. Syngeneic cells induced negligible neutrophil or Mφ responses. Neutrophils and Mφ induced by xenogeneic cells in SCID mice stimulated T cell recruitment after transfer to immunocompetent mice. T cells in turn were required for Mφ activation and xenogeneic cell rejection. Thus, Mφ harvested from immunocompetent but not SCID mice injected with xenogeneic cells expressed activation markers and rejected xenogeneic cells when transferred into SCID mice. These findings demonstrate the interdependent roles of Mφ and T cells in xenograft rejection. The requirement for Mφ reflects their ability to mount a rapid, local innate response that stimulates T cell recruitment and, having received T cell help, to act as direct effectors of rejection.

Effects of dietary antioxidants on training and performance in female runners

Abstract Exercise-induced oxidative stress is implicated in muscle damage and fatigue which has led athletes to embark on antioxidant supplementation regimes to negate these effects. This study investigated the intake of vitamin C (VC) (1 g), blackcurrant (BC) juice (15 mg VC, 300 mg anthocyanins) and placebo in isocaloric drink form on training progression, incremental running test and 5-km time-trial performance. Twenty-three trained female runners (age, 31±8 y; mean±SD) completed three blocks of high-intensity training for 3 wks and 3 days, separated by a washout (~3.7 wks). Changes in training and performance with each treatment were analysed with a mixed linear model, adjusting for performance at the beginning of each training block. Markers of oxidative status included protein carbonyl, malondialdehyde (in plasma and in vitro erythrocytes), ascorbic acid, uric acid and erythrocyte enzyme activity of superoxide dismutase, catalase and glutathione peroxidase were analysed. There was a likely harmful effect on mean running speed during training when taking VC (1.3%; 90% confidence limits ±1.3%). Effects of the two treatments relative to placebo on mean performance in the incremental test and time trial were unclear, but runners faster by 1 SD of peak speed demonstrated a possible improvement on peak running speed with BC juice (1.9%; ±2.5%). Following VC, certain oxidative markers were elevated: catalase at rest (23%; ±21%), protein carbonyls at rest (27%; ±38%) and superoxide dismutase post-exercise (8.3%; ±9.3%). In conclusion, athletes should be cautioned about taking VC chronically, however, BC may improve performance in the elite.

Effect of Vitamin C Supplements on Physical Performance

Vitamin C is an essential component of the diet and may reduce the adverse effects of exercise-induced reactive oxygen species, including muscle damage, immune dysfunction, and fatigue. However, reactive oxygen species may mediate beneficial training adaptations that vitamin C attenuates; indeed, from a total of 12 studies, vitamin C in doses >1 g·d−1 impaired sport performance substantially in four of four studies, possibly by reducing mitochondrial biogenesis, while a further four studies demonstrated impairments that were not statistically significant. Doses of ∼0.2 g·d−1 of vitamin C consumed through five or more servings of fruit and vegetables may be sufficient to reduce oxidative stress and provide other health benefits without impairing training adaptations.

Reducing Breast Cancer Recurrence: The Role of Dietary Polyphenolics.

Evidence from numerous observational and clinical studies suggest that polyphenolic phytochemicals such as phenolic acids in olive oil, flavonols in tea, chocolate and grapes, and isoflavones in soy products reduce the risk of breast cancer. A dietary food pattern naturally rich in polyphenols is the Mediterranean diet and evidence suggests those of Mediterranean descent have a lower breast cancer incidence. Whilst dietary polyphenols have been the subject of breast cancer risk-reduction, this review will focus on the clinical effects of polyphenols on reducing recurrence. Overall, we recommend breast cancer patients consume a diet naturally high in flavonol polyphenols including tea, vegetables (onion, broccoli), and fruit (apples, citrus). At least five servings of vegetables and fruit daily appear protective. Moderate soy protein consumption (5–10 g daily) and the Mediterranean dietary pattern show the most promise for breast cancer patients. In this review, we present an overview of clinical trials on supplementary polyphenols of dietary patterns rich in polyphenols on breast cancer recurrence, mechanistic data, and novel delivery systems currently being researched.

The effect of flavonoids on visual function in patients with glaucoma or ocular hypertension: a systematic review and meta-analysis

BackgroundGlaucoma is a leading cause of irreversible blindness worldwide. A major symptom of this pathology is the loss to the visual field in a peripheral to central pattern. Flavonoids are polyphenol compounds sourced from plants, commonly found in green tea, red wine and cocoa, and they have neuroprotective and antioxidant characteristics proposed to be advantageous within the context of glaucoma. Currently, the literature presents conflicting evidence regarding the effect of flavonoids on patients with glaucoma and ocular hypertension; hence a systematic review and meta-analysis was conducted.MethodDatabases included in our literature search were EMBASE (1980-present), MEDLINE Ovid, Alternative and Complementary Medicine Database (AMED), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Central Register of Controlled Trials (CENTRAL). Meta-analysis was performed using RevMan 5 (Review Manager) 5 software, version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen). The primary outcomes were visual field mean deviation (MD) and intraocular pressure (IOP). Secondary outcomes were ocular blood flow and blood pressure (BP).ConclusionMeta-analyses showed that flavonoids have a promising role in improving visual function in patients with glaucoma and ocular hypertension (OHT), and appear to play a part in both improving and slowing the progression of visual field loss.

T-cells and their cytokine production: The anti-inflammatory and immunosuppressive effects of strenuous exercise

ABSTRACT Strenuous exercise bouts and heavy training are associated with a heightened anti‐inflammatory state and a transient suppression of several immune components. In turn, many athletes are susceptible to illness, particularly upper respiratory symptoms (e.g. cough, sore throat, running nose). T‐lymphocytes (T‐cells) are important for orchestrating the immune response and can be categorised into subsets according to their phenotypical characteristics resulting from polarisation (i.e. type‐1, type‐2 and regulatory T‐cells). Each T‐cell subset has a unique functional role, including their capacity to produce pro‐ and anti‐inflammatory cytokines in response to an immune challenge. Prolonged and exhaustive exercise typically reduces peripheral blood type‐1 T‐cell number and their capacity to produce the pro‐inflammatory cytokine, interferon‐&ggr;. Moreover, heavy training loads are associated with elevated numbers of resting peripheral blood type‐2 and regulatory T‐cells, which characteristically produce the anti‐inflammatory cytokines, interleukin‐4 and interleukin‐10, respectively. This appears to increase the risk of upper respiratory symptoms, potentially due to the cross‐regulatory effect of interleukin‐4 on interferon‐&ggr; production and immunosuppressive action of IL‐10. Catecholamines significantly influence the number of peripheral blood T‐cells in response to exercise. Whereas, glucocorticoids and prostaglandin E2 promote the production of anti‐inflammatory cytokines by T‐cells. In summary, strenuous exercise bouts and heavy training shifts T‐cell immunity towards an anti‐inflammatory state. This impairs the ability of the immune system to mount an inflammatory response to an immune challenge, which may weaken defences against intracellular pathogens (e.g. viruses), and increase the risk of infection and viral reactivation.

Effect of Flavonoids on Upper Respiratory Tract Infections and Immune Function: A Systematic Review and Meta-Analysis

Previous research on animals indicates flavonoid compounds have immunomodulatory properties; however, human research remains inconclusive. The aim of this systematic review was to assess the efficacy of dietary flavonoids on upper respiratory tract infections (URTIs) and immune function in healthy adults. A created search strategy was run against Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and EMBASE classic, CINAHL, and AMED. The returned studies were initially screened, and 2 reviewers independently assessed the remaining studies for eligibility against prespecified criteria. Fourteen studies, of 387 initially identified, were included in this review, and the primary outcome measure was the effect of flavonoids on URTI incidence, duration, and severity. Of the included studies, flavonoid supplementation ranged from 0.2 to 1.2 g/d. Overall, flavonoid supplementation decreased URTI incidence by 33% (95% CI: 31%, 36%) compared with control, with no apparent adverse effects. Sick-day count was decreased by 40% with flavonoid supplementation, although unclear. Differences in bio-immune markers (e.g., interleukin-6, tumor necrosis factor-α, interferon-γ, neutrophils) were trivial between the intervention and control groups during the intervention and after exercise when a postintervention exercise bout was included. These findings suggest that flavonoids are a viable supplement to decrease URTI incidence in an otherwise healthy population.

Malignant Mesothelioma and Delivery of Polyphenols

Malignant Mesothelioma (MM) is a rare form of cancer that affects the thin cell wall lining of the bodys internal organs and structures.[...].

Determining the efficacy of the chronic disease self-management programme and readability of 'living a healthy life with chronic conditions' in a New Zealand setting.

Self‐management programmes are an increasingly popular way of treating chronic diseases.

Food components and ocular pathophysiology: a critical appraisal of the role of oxidative mechanisms

BACKGROUND AND OBJECTIVES Three of the major ocular diseases, namely cataracts, age-related macular degeneration and glaucoma are associated with oxidative damage. Disease risk and progression may be reduced through consumption of dietary components. To critically examine the literature on dietary and supplemental intakes of fruit and vegetables, meat, antioxidants (vitamins C, E and A), calcium, folate, iron, and their association with ocular disease. METHODS AND STUDY DESIGN Google Scholar and key references from texts and publications were searched using search terms (eye disease, antioxidants), (vision, nutrition), no date restriction, only articles in English were included. RESULTS We found probable evidence that dietary intake of fruits and vegetables, and vitamin C lowered incidence of cataracts and age-related macular degeneration. In high supplemental doses, vitamin C increases macular degeneration risk. Vitamin A from food was protective for cataracts and glaucoma, but not in supplemental form. Vitamin A was associated with lower incidence of macular degeneration. We also found probable evidence that higher intakes of meat increased the risk of cataracts and macular degeneration. Dietary calcium and iron appeared protective against glaucoma, but not in supplemental form. CONCLUSIONS While a nutrient rich diet high in fruit and vegetables, and associated antioxidants appeared to be protective, we would caution intake of supplementary antioxidants for those with ocular disease.