Studies on antigen-induced arthritis: antigen handling and inflammation

Contains fulltext : mmubn000001_026975009.pdf (publisher's version ) (Open Access)Promotor : L. van de Putte127 p

Patients' preferences for visuals: Differences in the preferred level of detail, type of background and type of frame of icons depicting organs between literate and low-literate people

Personalised Therapeutic

Side effects of azathioprine treatment in Rheumatoid Arthritis: analysis of 10 years of experience

Our experience with azathioprine in the treatment of rheumatoid arthritis covers ten years, during which 91 rheumatoid patients (66 female and 25 male) received this drug, with a median treatment period of 36 months. Total follow-up experience, during and after treatment, was 399 person years. Twelve patients died. The principal causes of death were malignant neoplasm (six patients) and cardiovascular diseases (three patients). The mortality in our patients was compared to that of the general Dutch population by the Standardised Mortality Ratio (SMR). In the male patient group a significant excess of both total mortality and mortality from malignancy was observed. The female patients showed no differences from the general population. In this follow-up study, no lymphoreticular tumours occurred during or after azathioprine therapy

Kwaliteitsnormen Nederlandse Vereniging voor Reumatologie

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Reduced thiopurine methyltransferase activity and development of side effects of azathioprine in the treatment of rheumatoid arthritis

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Enhanced angiotensin II degradation in porcine coronary neointimal hyperplasia induced by stent implantation

Background: Angiotensin II (Ang II) has been proposed as a modulator of growth factor responses in the arterial wall. Employing a model of stent- induced neointimal hyperplasia, we studied angiotensin I (Ang I) elimination. Methods: Balloon-expandable radiopaque stents (n=6) were implanted in coronary arteries of pigs. After 3 months, the stented and nonstented (control) vessels were studied in vitro for their conversion of radiolabeled 125I-Ang I to 125I-Ang II in the presence or absence of captopril. Conversion was also studied after removal of the endothelium. Results: Immunocytochemistry confirmed the presence of endothelium covering the neointima. Stented vessels metabolized 125I-Ang I faster and released less 125I-Ang II than normal arteries. 125I-Ang I formation could be completely blocked by captopril, but only up to 75% by removal of the endothelium. Determination of the rate constants for elimination of 125I- Ang I revealed that the reduced release of 125I-Ang II appeared not to be due to decreased conversion by angiotensin-converting enzyme in stented vessels, but merely to increased degradation. Conclusions: Porcine coronary arteries up to 3 months after stent implantation release significantly less 125I-Ang II upon challenge with 125I-Ang I. A higher degradation of 125I-Ang II in the stented coronary arterial wall may explain this finding. Enhanced degradation of pro-, but likely also of antiproliferative, peptide growth factors locally in the vessel wall may further complicate our understanding of neointimal proliferation after arterial damage.</p

Enhanced angiotensin II degradation in porcine coronary neointimal hyperplasia induced by stent implantation

Background: Angiotensin II (Ang II) has been proposed as a modulator of growth factor responses in the arterial wall. Employing a model of stent- induced neointimal hyperplasia, we studied angiotensin I (Ang I) elimination. Methods: Balloon-expandable radiopaque stents (n=6) were implanted in coronary arteries of pigs. After 3 months, the stented and nonstented (control) vessels were studied in vitro for their conversion of radiolabeled 125I-Ang I to 125I-Ang II in the presence or absence of captopril. Conversion was also studied after removal of the endothelium. Results: Immunocytochemistry confirmed the presence of endothelium covering the neointima. Stented vessels metabolized 125I-Ang I faster and released less 125I-Ang II than normal arteries. 125I-Ang I formation could be completely blocked by captopril, but only up to 75% by removal of the endothelium. Determination of the rate constants for elimination of 125I- Ang I revealed that the reduced release of 125I-Ang II appeared not to be due to decreased conversion by angiotensin-converting enzyme in stented vessels, but merely to increased degradation. Conclusions: Porcine coronary arteries up to 3 months after stent implantation release significantly less 125I-Ang II upon challenge with 125I-Ang I. A higher degradation of 125I-Ang II in the stented coronary arterial wall may explain this finding. Enhanced degradation of pro-, but likely also of antiproliferative, peptide growth factors locally in the vessel wall may further complicate our understanding of neointimal proliferation after arterial damage.</p

Mobility, turnover and storage of pollutants in soils, sediments and waters : achievements and results of the EU project AquaTerra : a review.

AquaTerra is one of the first environmental projects within the 6th Framework program by the European Commission. It began in June 2004 with a multidisciplinary team of 45 partner organizations from 13 EU countries, Switzerland, Serbia, Romania and Montenegro. Results from sampling and modeling in 4 large river basins (Ebro, Danube, Elbe and Meuse) and one catchment of the Brévilles Spring in France led to new evaluations of diffuse and hotspot input of persistent organic and metal pollutants including dynamics of pesticides and polycyclic aromatic hydrocarbons, as well as metal turnover and accumulation. While degradation of selected organic compounds could be demonstrated under controlled conditions in the laboratory, turnover of most persistent pollutants in the field seems to range from decades to centuries. First investigations of long-term cumulative and degradation effects, particularly in the context of climate change, have shown that it is also necessary to consider the predictions of more than one climate model when trying to assess future impacts. This is largely controlled by uncertainties in climate model responses. It is becoming evident, however, that changes to the climate will have important impacts on the diffusion and degradation of pollutants in space and time that are just at the start of their exploration

Local endothelial DNA repair defect causes aging-resembling endothelial-specific dysfunction

We previously identified genomic instability as a causative factor for vascular aging. In the present study determined which vascular aging outcomes are due to local endothelial DNA damage, which was accomplished by genetic removal of ERCC1 DNA repair in mice (EC-KO mice). EC-KO showed a progressive decrease in microvascular dilation of the skin, increased microvascular leakage in the kidney, decreased lung perfusion, and increased aortic stiffness compared to WT. EC-KO showed expression of DNA damage and potential senescence marker p21 exclusively in the endothelium, as demonstrated in aorta. Also the kidney showed p21-positive cells. Vasodilator responses measured in organ baths were decreased in aorta, iliac and coronary artery EC-KO compared to WT, of which coronary artery was the earliest to be affected. Nitric oxide-mediated endothelium-dependent vasodilation was abolished in aorta and coronary artery, whereas endothelium-derived hyperpolarization and responses to exogenous nitric oxide were intact. EC-KO showed increased superoxide production compared to WT, as measured in lung tissue, rich in endothelial cells. Arterial systolic blood pressure was increased at 3 months, but normal at 5 months, at which age cardiac output was decreased. Since no further signs of cardiac dysfunction were detected this decrease might be an adaptation to prevent an increase of blood pressure. In summary, a selective DNA repair defect in the endothelium produces features of age-related endothelial dysfunction, largely attributed to loss of endothelium-derived nitric oxide. Increased superoxide generation might contribute to the observed changes affecting end organ perfusion, as demonstrated in kidney and lung