53 research outputs found
Construction of alkyl-substituted pentaphosphido ligands in the coordination sphere of cobalt
Cardiac Myxoma and Cerebrovascular Events: A Retrospective Cohort Study
Background: Cardiac myxoma (CM) is the most frequent, cardiac benign tumor and is associated with enhanced risk for cerebrovascular events (CVE). Although surgical CM excision is the only curative treatment to prevent CVE recurrence, in recent reports conservative treatment with antiplatelet or anticoagulant agents in high-risk patients with CM-related CVE has been discussed.Methods: Case records at the University Hospital of TĂŒbingen between 2005 and 2017 were screened to identify patients with CM-related CVE. Clinical features, brain and cardiac imaging findings, histological reports, applied treatments and long-term neurological outcomes were assessed.Results: 52 patients with CM were identified and among them, 13 patients with transient ischemic attack, ischemic stroke or retinal ischemia were included to the (to our knowledge) largest reported retrospective study of CM-related CVE. In all identified patients, CVE was the first manifestation of CM; 61% suffered ischemic stroke, 23% transient ischemic attack and 15% retinal ischemia. In 46% of the patients, CVE occurred under antiplatelet or anticoagulation treatment, while 23% of the patients developed recurrent CVE under bridging-antithrombotic-therapy prior to CM surgical excision. Prolonged time interval between CVE and CM-surgery was significantly associated with CVE recurrence (p = 0.021). One patient underwent i.v. thrombolysis, followed by thrombectomy, with good post-interventional outcome and no signs of hemorrhagic transformation.Discussion: Our results suggest that antiplatelet or anticoagulation treatment is no alternative to cardiac surgery in patients presenting with CM-related CVE. We found significantly prolonged time-intervals between CVE and CM surgery in patients with recurrent CVE. Therefore, we suggest that the waiting- or bridging-interval with antithrombotic therapy until curative CM excision should be kept as short as possible. Based on our data and review of the literature, we suggest that in patients with CM-related CVE, i.v. thrombolysis and/or endovascular interventions may present safe and efficacious acute treatments
Recent advances in food allergy
Food allergy is a public health issue that has significantly increased worldwide in the past decade, affecting consumersâ quality of life and making increasing demands on health service resources. Despite recent advances in many areas of diagnosis and treatment, our general knowledge of the basic mechanisms of the disease remain limited i.e., not at pace with the exponential number of new cases and the explosion of new technologies. Many important key questions remain: What defines a major allergen? Why do some individuals develop food allergies and others do not? Which are the environmental factors? Could the environmental factors be monitored through epigenetics or modified by changes in the microbiome? Can tolerance to food be induced? Why are some foods more likely to trigger allergies than others? Does the route and timing of exposure have any role on sensitization? These and many other related questions remain unanswered. In this short review some of these topics are addressed in the light of recent advances in the area
Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets
<p>Abstract</p> <p>Background</p> <p>Flavonoids, a large group of polyphenolic metabolites derived from plants have received a great deal of attention over the last several decades for their properties in inflammation and allergy. Quercetin, the most abundant of plant flavonoids, exerts a modulatory action at nanomolar concentrations on human basophils. As this mechanism needs to be elucidated, in this study we focused the possible signal transduction pathways which may be affected by this compound. Methods: K2-EDTA derived leukocyte buffy coats enriched in basophil granulocytes were treated with different concentrations of quercetin and triggered with anti-IgE, fMLP, the calcium ionophore A23187 and the phorbol ester PMA in different experimental conditions. Basophils were captured in a flow cytometry analysis as CD123bright/HLADRnon expressing cells and fluorescence values of the activation markers CD63-FITC or CD203c-PE were used to produce dose response curves. The same population was assayed for histamine release.</p> <p>Results</p> <p>Quercetin inhibited the expression of CD63 and CD203c and the histamine release in basophils activated with anti-IgE or with the ionophore: the IC50 in the anti-IgE model was higher than in the ionophore model and the effects were more pronounced for CD63 than for CD203c. Nanomolar concentrations of quercetin were able to prime both markers expression and histamine release in the fMLP activation model while no effect of quercetin was observed when basophils were activated with PMA. The specific phosphoinositide-3 kinase (PI3K) inhibitor wortmannin exhibited the same behavior of quercetin in anti-IgE and fMLP activation, thus suggesting a role for PI3K involvement in the priming mechanism.</p> <p>Conclusions</p> <p>These results rule out a possible role of protein kinase C in the complex response of basophil to quercetin, while indirectly suggest PI3K as the major intracellular target of this compound also in human basophils.</p
Differential response of human basophil activation markers: a multi-parameter flow cytometry approach
<p>Abstract</p> <p>Background</p> <p>Basophils are circulating cells involved in hypersensitivity reactions and allergy but many aspects of their activation, including the sensitivity to external triggering factors and the molecular aspects of cell responses, are still to be focused. In this context, polychromatic flow cytometry (PFC) is a proper tool to investigate basophil function, as it allows to distinguish the expression of several membrane markers upon activation in multiple experimental conditions. </p> <p>Methods</p> <p>Cell suspensions were prepared from leukocyte buffy coat of K2-EDTA anticoagulated blood specimens; about 1500-2500 cellular events for each tested sample, gated in the lymphocyte CD45dim area and then electronically purified as HLADRnon expressing/CD123bright, were identified as basophilic cells. Basophil activation with fMLP, anti-IgE and calcium ionophore A23187 was evaluated by studying up-regulation of the indicated membrane markers with a two-laser six-color PFC protocol.</p> <p>Results</p> <p>Following stimulation, CD63, CD13, CD45 and the ectoenzyme CD203c up-regulated their membrane expression, while CD69 did not; CD63 expression occurred immediately (within 60 sec) but only in a minority of basophils, even at optimal agonist doses (in 33% and 14% of basophils, following fMLP and anti-IgE stimulation respectively). CD203c up-regulation occurred in the whole basophil population, even in CD63non expressing cells. Dose-dependence curves revealed CD203c as a more sensitive marker than CD63, in response to fMLP but not in response to anti-IgE and to calcium ionophore.</p> <p>Conclusion</p> <p>Use of polychromatic flow cytometry allowed efficient basophil electronic purification and identification of different behaviors of the major activation markers. The simultaneous use of two markers of activation and careful choice of activator are essential steps for reliable assessment of human basophil functions.</p
Penumbral Rescue by normobaric O = O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial.
Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs.
PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion.
Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial.
Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted.
Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation.
By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia.
ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31
Using fish models to investigate the links between microbiome and social behaviour: the next step for translational microbiome research?
Recent research has revealed surprisingly important connections between animalsâ microbiome and social behaviour. Social interactions can affect the composition and function of the microbiome; conversely, the microbiome affects social communication by influencing the hostsâ central nervous system and peripheral chemical communication. These discoveries set the stage for novel research focusing on the evolution and physiology of animal social behaviour in relation to microbial transmission strategies. Here, we discuss the emerging roles of teleost fish models and their potential for advancing research fields, linked to sociality and microbial regulation. We argue that fish models, such as the zebrafish (Danio rerio, Cyprinidae), sticklebacks (âGasterosteidae), guppies (Poeciliidae) and cleanerâclient dyads (e.g., obligate cleaner fish from the Labridae and Gobiidae families and their visiting clientele), will provide valuable insights into the roles of microbiome in shaping social behaviour and vice versa, while also being of direct relevance to the food and ornamental fish trades. The diversity of fish behaviour warrants more interdisciplinary research, including microbiome studies, which should have a strong ecological (fieldâderived) approach, together with laboratoryâbased cognitive and neurobiological experimentation. The implications of such integrated approaches may be of translational relevance, opening new avenues for future investigation using fish models
Biomarkers of the involvement of mast cells, basophils and eosinophils in asthma and allergic diseases
Biomarkers of the involvement of mast cells, basophils and eosinophils in asthma and allergic diseases
Biomarkers of disease activity have come into wide use in the study of mechanisms of human disease and in clinical medicine to both diagnose and predict disease course; as well as to monitor response to therapeutic intervention. Here we review biomarkers of the involvement of mast cells, basophils, and eosinophils in human allergic inflammation. Included are surface markers of cell activation as well as specific products of these inflammatory cells that implicate specific cell types in the inflammatory process and are of possible value in clinical research as well as within decisions made in the practice of allergy-immunology
Deutsch-SĂŒdtirol
von F.K. HennersdorfSchriftenreihe des Originals: Taschenbuch des Grenz- und Auslanddeutschtums ; Heft 35In Fraktu
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