107 research outputs found

    Catecholaminergic signalling through thymic nerve fibres, thymocytes and stromal cells is dependent on both circulating and locally synthesized glucocorticoids

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    Glucocorticoids have been shown to modulate the expression of noradrenaline metabolizing enzymes and beta(2)- and alpha(1B)-adrenoceptors in a tissue- and cell- specific manner. In the thymus, apart from extensive sympathetic innervation, a regulatory network has been identified that encompasses catecholamine-containing non-lymphoid and lymphoid cells. We examined a putative role of adrenal- and thymus-derived glucocorticoids in modulation of rat thymic noradrenaline levels and adrenoceptor expression. Seven days postadrenalectomy, the thymic levels of mRNAs encoding tyrosine hydroxylase, dopamine beta-hydroxylase, monoamine oxidase-A and, consequently, noradrenaline were decreased. Catecholamine content was diminished in autofluorescent nerve fibres (judging by the intensity of fluorescence) and thymocytes (considering HPLC measurements of noradrenaline and the frequency of tyrosine hydroxylase-positive cells), while it remained unaltered in non-lymphoid autofluorescent cells. In addition, adrenalectomy diminished the thymocyte expression of beta(2)- and alpha(1B)-adrenoceptors at both mRNA and protein levels. Administration of ketoconazole (an inhibitor of glucocorticoid synthesis/action; 25 mg kg(-1) day(-1), s.c.) to glucocorticoid-deprived rats increased the thymic levels of tyrosine hydroxylase, dopamine beta-hydroxylase and, consequently, noradrenaline. The increased intensity of the autofluorescent cell fluorescence in ketoconazole-treated rats indicated an increase in their catecholamine content, and suggested differential glucocorticoid-mediated regulation of catecholamines in thymic lymphoid and non-lymphoid cells. In addition, ketoconazole increased the thymocyte expression of alpha(1B)-adrenoceptors. Thus, this study indicates that in the thymus, as in some other tissues, glucocorticoids not only act in concert with cateholamines, but they may modulate catecholamine action by tuning thymic catecholamine metabolism and adrenoceptor expression in a cell-specific manner. Additionally, the study indicates a role of thymus-derived glucocorticoids in this modulation

    Effect of exercise on fluoride metabolism in adult humans: a pilot study

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    An understanding of all aspects of fluoride metabolism is critical to identify its biological effects and avoid fluoride toxicity in humans. Fluoride metabolism and subsequently its body retention may be affected by physiological responses to acute exercise. This pilot study investigated the effect of exercise on plasma fluoride concentration, urinary fluoride excretion and fluoride renal clearance following no exercise and three exercise intensity conditions in nine healthy adults after taking a 1-mg Fluoride tablet. After no, light, moderate and vigorous exercise, respectively, the mean (SD) baseline-adjusted i) plasma fluoride concentration was 9.6(6.3), 11.4(6.3), 15.6(7.7) and 14.9(10.0) ng/ml; ii) rate of urinary fluoride excretion over 0–8 h was 46(15), 44(22), 34(17) and 36(17) μg/h; and iii) rate of fluoride renal clearance was 26.5(9.0), 27.2(30.4), 13.1(20.4) and 18.3(34.9) ml/min. The observed trend of a rise in plasma fluoride concentration and decline in rate of fluoride renal clearance with increasing exercise intensity needs to be investigated in a larger trial. This study, which provides the first data on the effect of exercise with different intensities on fluoride metabolism in humans, informs sample size planning for any subsequent definitive trial, by providing a robust estimate of the variability of the effect

    Cancer Carepartners: Improving patients' symptom management by engaging informal caregivers

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    <p>Abstract</p> <p>Background</p> <p>Previous studies have found that cancer patients undergoing chemotherapy can effectively manage their own symptoms when given tailored advice. This approach, however, may challenge patients with poor performance status and/or emotional distress. Our goal is to test an automated intervention that engages a friend or family member to support a patient through chemotherapy.</p> <p>Methods/Design</p> <p>We describe the design and rationale of a randomized, controlled trial to assess the efficacy of 10 weeks of web-based caregiver alerts and tailored advice for helping a patient manage symptoms related to chemotherapy. The study aims to test the primary hypothesis that patients whose caregivers receive alerts and tailored advice will report less frequent and less severe symptoms at 10 and 14 weeks when compared to patients in the control arm; similarly, they will report better physical function, fewer outpatient visits and hospitalizations related to symptoms, and greater adherence to chemotherapy. 300 patients with solid tumors undergoing chemotherapy at two Veteran Administration oncology clinics reporting any symptom at a severity of ≥4 and a willing informal caregiver will be assigned to either 10 weeks of automated telephonic symptom assessment (ATSA) alone, or 10 weeks of ATSA plus web-based notification of symptom severity and problem solving advice to their chosen caregiver. Patients and caregivers will be surveyed at intake, 10 weeks and 14 weeks. Both groups will receive standard oncology, hospice, and palliative care.</p> <p>Discussion</p> <p>Patients undergoing chemotherapy experience many symptoms that they may be able to manage with the support of an activated caregiver. This intervention uses readily available technology to improve patient caregiver communication about symptoms and caregiver knowledge of symptom management. If successful, it could substantially improve the quality of life of veterans and their families during the stresses of chemotherapy without substantially increasing the cost of care.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00983892">NCT00983892</a></p

    Preventive Antibacterial Therapy in Acute Ischemic Stroke: A Randomized Controlled Trial

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    BACKGROUND: Pneumonia is a major risk factor of death after acute stroke. In a mouse model, preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections, it also reduces mortality, and improves neurological outcome significantly. In this study we investigate whether this approach is effective in stroke patients. METHODS: Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) is a randomized, double-blind, placebo-controlled trial in 80 patients with severe, non-lacunar, ischemic stroke (NIHSS>11) in the middle cerebral artery (MCA) territory. Patients received either intravenous moxifloxacin (400 mg daily) or placebo for 5 days starting within 36 hours after stroke onset. Primary endpoint was infection within 11 days. Secondary endpoints included neurological outcome, survival, development of stroke-induced immunodepression, and induction of bacterial resistance. FINDINGS: On intention-to treat analysis (79 patients), the infection rate at day 11 in the moxifloxacin treated group was 15.4% compared to 32.5% in the placebo treated group (p = 0.114). On per protocol analysis (n = 66), moxifloxacin significantly reduced infection rate from 41.9% to 17.1% (p = 0.032). Stroke associated infections were associated with a lower survival rate. In this study, neurological outcome and survival were not significantly influenced by treatment with moxifloxacin. Frequency of fluoroquinolone resistance in both treatment groups did not differ. On logistic regression analysis, treatment arm as well as the interaction between treatment arm and monocytic HLA-DR expression (a marker for immunodepression) at day 1 after stroke onset was independently and highly predictive for post-stroke infections. INTERPRETATION: PANTHERIS suggests that preventive administration of moxifloxacin is superior in reducing infections after severe non-lacunar ischemic stroke compared to placebo. In addition, the results emphasize the pivotal role of immunodepression in developing post-stroke infections. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN74386719

    A double-blind, randomized controlled trial to compare the effect of biannual peripheral magnetic resonance imaging, radiography and standard of care disease progression monitoring on pharmacotherapeutic escalation in rheumatoid and undifferentiated inflammatory arthritis: study protocol for a randomized controlled trial

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    Integrated Multi-Parameter Exploration Footprints of the Canadian Malartic Disseminated Au, McArthur River-Millennium Unconformity U, and Highland Valley Porphyry Cu Deposits: Preliminary Results from the NSERC-CMIC Mineral Exploration Footprints Research Network

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    Mineral exploration in Canada is increasingly focused on concealed and deeply buried targets, requiring more effective tools to detect large-scale ore-forming systems and to vector from their most distal margins to their high grade cores. A new generation of ore system models is required to achieve this. The Mineral Exploration Footprints Research Network is a consortium of 70 faculty, research associates, and students from 20 Canadian universities working with 30 mining, mineral exploration, and mining service providers to develop new approaches to ore system modelling based on more effective integration and visualization of multi-parameter geological-structural-mineralogical-lithogeochemical-petrophysical-geophysical exploration data. The Network is developing the next generation ore system models and exploration strategies at three sites based on integrated data visualization using self-consistent 3D Common Earth Models and geostatistical/machine learning technologies. Thus far over 60 footprint components and vectors have been identified at the Canadian Malartic stockwork-disseminated Au deposit, 20–30 at the McArthur-Millennium unconformity U deposits, and over 20 in the Highland Valley porphyry Cu system. For the first time, these are being assembled into comprehensive models that will serve as landmark case studies for data integration and analysis in the today’s challenging exploration environment
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