View clinical trials related to Pathophysiology.
Filter by:Background / rationale: Type 2 inflammation is driving several chronic diseases in the airway. On one hand allergic rhinitis (AR) and allergic asthma (AA) are driven by allergen expose, while on the other hand eosinophilic Type 2 inflammation with late onset eosinophilic asthma (LOA) and chronic rhinosinusitis with nasal polyps (CRSwNP) are of non-allergic ethiology. For late onset type2 asthma, many risk factors have been defined, but clear insights into disease ethiology are currently lacking. Given the quintessential role of IgE in disease ethiology of both diseases, understanding the molecular immunological mechanisms underlying mucosal IgE responses is essential to understand disease ethiology. Hypothesis: Distinct mechanisms drive local IgE production in AA and LOA Overall objectives: Elucidate the potential drivers of and immunological pathways leading to local IgE production in AA and LOA, and understand how dupilumab acts on these mechanisms. Methods: A unique combination of state-of-the-art methods will be applied, including single-cell RNA sequencing and receptor profiling, proteomics, determination of the microbial composition, recombinant antibody screening and disease modelling in cell cultures. Expected results: The investigators expect for the first time to discern the drivers of local IgE production in LOA and uncover the immunological pathways leading to local IgE production in AA and LOA. Moreover, the investigators will obtain insights into the role of Dupilumab in modulation mechanisms. Impact: If successful, these insights will answer a long standing, unresolved question in type 2 disease and might aid in the development of novel directed therapeutics for AA and LOA.
The 'ADAPT' Biobank is a collection of body material and data from patients with or at risk of cardiac arrhythmias who underwent or will undergo (non-) invasive treatment for this disease. Its main objective is to obtain a comprehensive collection of patient information and material to facilitate research and gain better insight into the complex pathophysiology of the different arrhythmias, the multifactorial process, the heterogeneity in clinical presentation, and prognosis. Bodily material is used for biochemical marker assessments, histological and molecular analyses for research in cardiac arrhythmias.
Insulin resistance and beta cell dysfunction are the major core defects responsible for the development of type 2 diabetes (T2DM). Although insulin resistance is the early metabolic defect detected in subjects destined to develop T2DM, it is the beta cell failure which is responsible for the development of hyperglycemia. Longitudinal and cross-sectional studies have demonstrated that, initially, the compensatory hyperinsulinemia is sufficient to offset the insulin resistance and maintain normal glucose tolerance. However, when the beta cell fails to adequately compensate for the insulin resistance, glucose homeostasis deteriorates. Initially, this is manifest as impaired glucose tolerance (IGT) and later as overt diabetes. It follows that the level of beta cell failure at which hyperglycemia becomes evident depends upon the prevailing level of insulin resistance. A more severe insulin resistance results in development of overt hyperglycemia at lower level of beta cell failure. The investigators previously have shown that the severity of insulin resistance varies amongst different ethnic groups (Arabs versus Indians). Thus, the level of beta cell failure at which overt hyperglycemia becomes evident amongst each ethnic group also varies. Thus, individuals/ethnic groups with more severe insulin resistance, overt hyperglycemia becomes evident at lower level of beta cell dysfunction. Conversely, severe beta cell dysfunction is required for evert hyperglycemia to develop in individuals/ethnicities with less severe insulin resistance. In the present study, the investigators aim to quantitate beta cell function with the gold standard technique (i.e. hyperglycemic clamp) in Arab and Indian non-diabetic individuals and relate the level of beta cell function to the prevailing level of insulin resistance measured as the glucose infusion rate divided by the mean plasma insulin concentration during the clamp.
To evaluate the effects of the temporomandibular disorder (TMD) and its therapeutic care on postural control in somato-sensory and visual sensitization compared to control subjects matched on age, sex and lifestyle. Parameters will be estimated by measures realized before the therapeutic care of the TMD (T0), then 2, 3 and 5 months after the starting care, both in TMD patients and control subjects. To evaluate also the effects of the TMD and its therapeutic care on balance control in various contexts of multi-sensory stimulation, orientation function, pain and tinnitus.