1,621 research outputs found

    Pro-oxidant effect of α-tocopherol in patients with Type 2 Diabetes after an oral glucose tolerance test – a randomised controlled trial

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    BACKGROUND: As a part of a larger study investigating the effects of α-tocopherol on gene expression in type 2 diabetics we observed a pro-oxidant effect of α-tocopherol which we believe may be useful in interpreting outcomes of large intervention trials of α-tocopherol. METHODS: 19 type 2 diabetes subjects were randomised into two groups taking either 1200 IU/day of α-tocopherol or a matched placebo for 4 weeks. On day 0 and 29 of this study oxidative DNA damage was assessed in mononuclear cells from fasted blood samples and following a 2 h glucose tolerance test (GTT). RESULTS: On day 0 there was no significant difference in oxidative DNA damage between the two groups or following a GTT. On day 29 there was no significant difference in oxidative DNA damage in fasted blood samples, however following a GTT there was a significant increase in oxidative DNA damage in the α-tocopherol treatment group. CONCLUSION: High dose supplementation with α-tocopherol primes mononuclear cells from patients with type 2 diabetes for a potentially damaging response to acute hyperglycaemia

    Volumetric quantitative optical coherence elastography with an iterative inversion method

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    It is widely accepted that accurate mechanical properties of three-dimensional soft tissues and cellular samples are not available on the microscale. Current methods based on optical coherence elastography can measure displacements at the necessary resolution, and over the volumes required for this task. However, in converting this data to maps of elastic properties, they often impose assumptions regarding homogeneity in stress or elastic properties that are violated in most realistic scenarios. Here, we introduce novel, rigorous, and computationally efficient inverse problem techniques that do not make these assumptions, to realize quantitative volumetric elasticity imaging on the microscale. Specifically, we iteratively solve the three-dimensional elasticity inverse problem using displacement maps obtained from compression optical coherence elastography. This is made computationally feasible with adaptive mesh refinement and domain decomposition methods. By employing a transparent, compliant surface layer with known shear modulus as a reference for the measurement, absolute shear modulus values are produced within a millimeter-scale sample volume. We demonstrate the method on phantoms, on a breast cancer sample ex vivo, and on human skin in vivo. Quantitative elastography on this length scale will find wide application in cell biology, tissue engineering and medicine.Publisher PDFPeer reviewe

    Allergenicity assessment of genetically modified crops—what makes sense?

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    GM crops have great potential to improve food quality, increase harvest yields and decrease dependency on certain chemical pesticides. Before entering the market their safety needs to be scrutinized. This includes a detailed analysis of allergenic risks, as the safety of allergic consumers has high priority. However, not all tests currently being applied to assessing allergenicity have a sound scientific basis. Recent events with transgenic crops reveal the fallacy of applying such tests to GM crops

    The Co-Production of Sustainable Future Scenarios

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    Scenarios are a tool to develop plausible, coherent visions about the future and to foster anticipatory knowledge. We present the Sustainable Future Scenarios (SFS) framework and demonstrate its application through the Central Arizona-Phoenix Long-term Ecological Research (CAP LTER) urban site. The SFS approach emphasizes the co-development of positive and long-term alternative future visions. Through a collaboration of practitioner and academic stakeholders, this research integrates participatory scenario development, modeling, and qualitative scenario assessments. The SFS engagement process creates space to question the limits of what is normally considered possible, desirable, or inevitable in the face of future challenges. Comparative analyses among the future scenarios demonstrate trade-offs among regional and microscale temperature, water use, land-use change, and co-developed resilience and sustainability indices. SFS incorporate diverse perspectives in co-producing positive future visions, thereby expanding traditional future projections. The iterative, interactive process also creates opportunities to bridge science and policy by building anticipatory and systems-based decision-making and research capacity for long-term sustainability planning

    Consumption of a high-fat meal increased monocyte adhesion molecule expression and oxLDL phagocytosis: implications for cardiovascular disease risk?

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    Macrophage-derived foam cells are the predominant component of arterial plaques in the early stages of atherosclerosis. The deposition of arterial plaques is effected by several factors that are influenced by a person’s daily nutritional habits. One factor that poses a major risk for plaque development is high levels of plasma LDL resulting from the consumption of a high-fat meal. In order to understand how an individuals’ diet effects arterial plaque deposition via the process of foam cell formation, we measured the acute response in circulating monocyte activity after consuming a high-fat meal. Samples were acquired on a FlowSight (EMD Millipore) equipped with 405, 488, 642, and 785 nm lasers. Samples were analyzed in IDEAS software to identify pro-inflammatory (CD14+/16+) and classic (CD14+/16-) monocytes. We measured monocyte concentration, adhesion molecule expression, scavenger R expression, and oxLDL phagocytosis for 5 h postprandial. We found that consuming a high-fat meal caused an increase in pro-inflammatory monocyte concentration, adhesion molecule expression, monocyte phagocytosis of oxLDL, and CD36 expression in pro-inflammatory monocytes. These results suggest that consuming a high-fat meal increases the potential of monocytes to become foam cells for at least 5 h postprandial

    Investigation of optical coherence micro-elastography as a method to visualize micro-architecture in human axillary lymph nodes

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    This project is supported with funding from the Australian Research Council; and Cancer Council WA, which allowed us to develop the technology; Department of Health of Western Australia, National Breast Cancer Foundation (Australia); and the National Health and Medical Research Council, Australia, which allowed us to design and implement the clinical protocol, and to perform the clinical measurements.Background : Evaluation of lymph node involvement is an important factor in detecting metastasis and deciding whether to perform axillary lymph node dissection (ALND) in breast cancer surgery. As ALND is associated with potentially severe long term morbidity, the accuracy of lymph node assessment is imperative in avoiding unnecessary ALND. The mechanical properties of malignant lymph nodes are often distinct from those of normal nodes. A method to image the micro-scale mechanical properties of lymph nodes could, thus, provide diagnostic information to aid in the assessment of lymph node involvement in metastatic cancer. In this study, we scan axillary lymph nodes, freshly excised from breast cancer patients, with optical coherence micro-elastography (OCME), a method of imaging micro-scale mechanical strain, to assess its potential for the intraoperative assessment of lymph node involvement. Methods : Twenty-six fresh, unstained lymph nodes were imaged from 15 patients undergoing mastectomy or breast-conserving surgery with axillary clearance. Lymph node specimens were bisected to allow imaging of the internal face of each node. Co-located OCME and optical coherence tomography (OCT) scans were taken of each sample, and the results compared to standard post-operative hematoxylin-and-eosin-stained histology. Results : The optical backscattering signal provided by OCT alone may not provide reliable differentiation by inspection between benign and malignant lymphoid tissue. Alternatively, OCME highlights local changes in tissue strain that correspond to malignancy and are distinct from strain patterns in benign lymphoid tissue. The mechanical contrast provided by OCME complements the optical contrast provided by OCT and aids in the differentiation of malignant tumor from uninvolved lymphoid tissue. Conclusion : The combination of OCME and OCT images represents a promising method for the identification of malignant lymphoid tissue. This method shows potential to provide intraoperative assessment of lymph node involvement, thus, preventing unnecessary removal of uninvolved tissues and improving patient outcomes.Publisher PDFPeer reviewe

    Skin exposure promotes a Th2-dependent sensitization to peanut allergens

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    Sensitization to foods often occurs in infancy, without a known prior oral exposure, suggesting that alternative exposure routes contribute to food allergy. Here, we tested the hypothesis that peanut proteins activate innate immune pathways in the skin that promote sensitization. We exposed mice to peanut protein extract on undamaged areas of skin and observed that repeated topical exposure to peanut allergens led to sensitization and anaphylaxis upon rechallenge. In mice, this epicutaneous peanut exposure induced sensitization to the peanut components Ara h 1 and Ara h 2, which is also observed in human peanut allergy. Both crude peanut extract and Ara h 2 alone served as adjuvants, as both induced a bystander sensitization that was similar to that induced by the a topic dermatitis associated staphylococcal enterotoxin B. In cultured human keratinocytes and in murine skin, peanut extract directly induced cytokine expression. Moreover, topical peanut extract application induced an alteration dependent on the IL-33 receptor ST2 in skin-draining DCs, resulting in Th2 cytokine production from T cells. Together, our data support the hypothesis that peanuts are allergenic due to inherent adjuvant activity and suggest that skin exposure to food allergens contributes to sensitization to foods in early life

    Skin exposure promotes a Th2-dependent sensitization to peanut allergens

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    Sensitization to foods often occurs in infancy, without a known prior oral exposure, suggesting that alternative exposure routes contribute to food allergy. Here, we tested the hypothesis that peanut proteins activate innate immune pathways in the skin that promote sensitization. We exposed mice to peanut protein extract on undamaged areas of skin and observed that repeated topical exposure to peanut allergens led to sensitization and anaphylaxis upon rechallenge. In mice, this epicutaneous peanut exposure induced sensitization to the peanut components Ara h 1 and Ara h 2, which is also observed in human peanut allergy. Both crude peanut extract and Ara h 2 alone served as adjuvants, as both induced a bystander sensitization that was similar to that induced by the atopic dermatitisassociated staphylococcal enterotoxin B. In cultured human keratinocytes and in murine skin, peanut extract directly induced cytokine expression. Moreover, topical peanut extract application induced an alteration dependent on the IL-33 receptor ST2 in skin-draining DCs, resulting in Th2 cytokine production from T cells. Together, our data support the hypothesis that peanuts are allergenic due to inherent adjuvant activity and suggest that skin exposure to food allergens contributes to sensitization to foods in early life.The work was supported by NIH grants AI044236 (to H.A. Sampson and M.C. Berin), AI093577 (to M.C. Berin), and AI091655 (to K.M. Järvinen) and Environmental Protection Agency grant R834064 (to M.C. Berin). Clinical specimens were provided by the Jaffe Food Allergy Resource Initiative, funded by Food Allergy Research and Education.Peer Reviewe
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