title: | Oxidative stress profiling of an inflammation and pathogenesis of diseases |
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reg no: | ETF6588 |
project type: | Estonian Science Foundation research grant |
subject: |
3.1. Basic Medicine |
status: | accepted |
institution: | TU Faculty of Medicine |
head of project: | Mihkel Zilmer |
duration: | 01.01.2006 - 31.12.2009 |
description: | Recent seminal reviews concluded that projects targeted at combining and integrating multiple or large panels of biomarkers of oxidative stress (OxS) and inflammation are highly needed. Normal metabolic processes generate inflammation and OxS, which, however, may also have deleterious consequences. Prolonged/chronic inflammation contributes to the pathogenesis of many disease states and recent data, including our own studies, confirm more and more that profound severe OxS (high grade OxS) also has a strong disease/damage-related character. Investigations on both inflammation and OxS have been intensive, and a number of articles have been published about both phenomena. However, the characterization of the nature and role of both phenomena under different conditions has been carried out mainly in a separated manner. It means that a real conceptual view on linking the pathways/mechanisms of inflammation with OxS is still open, and so an area as important as the systemic targeted investigation of links (interactions) between inflammation and OxS has in the past and still suffers from the lack of enough scien¬tific attention. Particularly, information about links (interactions) concerning an ongoing/chronic inflammatory process and high grade OxS remains largely inconclusive, and existing information is not able to explain the actual role of integrated action concerning an ongoing inflammatory process and high grade OxS regarding damages and pathogeneses under different conditions. In this context, our project’s systemic and multilevel nature allows to get a conceptual view on links of chronic inflammation with high grade OxS, particularly concerning the pathogenesis of diseases. The importance, novelty and reality of the mentioned-above aims of this project is based on the following circumstances: 1) both prolonged inflammation and high grade OxS have a strong disease/damage-related character; 2) the complex characterization and investigation of relations/interactions between limited controlled inflammation and OxS and particularly links between an integrated action of ongoing inflammatory process and high grade OxS different conditions (cells, isolated heart model, clinical conditions like skin diseases, open heart surgery, endothelium dysfunctionality, arterial stiffness, chronic renal disease, CVD diseases, diabetes) by using contemporary high-technology (new reactive species analyzer Apollo 4000, Langendorff’s apparatus, MALDI-TOF mass-spectrometry, ELISA readers, SphygmoCor Px, version 7.0, HDI/Pulse WaveTM CR-2000, transgenic animals) for a concurrent assessment multivalent spectrum of indicative biomarkers characterizing OxS and/or inflammation (MPO, NADPH oxidase, oxLDL, autoantibody against oxLDL, adiponectin, ADMA, AGE, isoprostanes, glutathione redox status, Hcy, h-VECAM, h-ICAM, HO-1, PON, LDL-BDC, nitrotyrosine, NO, H2O2, TGF-beta, interferon-gamma, CD, MMPs, gamma-glutamyltransferase, hsCRP and other high-informative inflammation-related biomarkers, a special selected set of interleukines) should provide new general as well as new target-specific multivalent and both fundamentally and clinically relevant information; 3) we have the experience (37 articles are published during 3 last years about OxS), competence and international co-operation (Department of Medical Sciences, Renal Unit, University of Uppsala; Department of Neurotoxicology and Neurochemistry, University of Stockholm; Department of Geriatric Medicine, Huddinge University Hospital; Research Institute for Public Health, University of Kuopio, etc) needed for an OxS/inflammation investigation using different models and disease conditions. |
project group | ||||
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no | name | institution | position | |
1. | Kalle Kilk | |||
2. | Tiiu Kullisaar | |||
3. | Riina Mahlapuu | |||
4. | Aune Rehema | |||
5. | Ursel Soomets | |||
6. | Joel Starkopf | |||
7. | Kersti Zilmer | |||
8. | Mihkel Zilmer | Tartu Ülikool |