Osteoarthritis (OA) mainly affects the articular cartilage covering the bones. In this thesis we investigated the relation between levels of inflammatory mediators, genes involved in their... Show moreOsteoarthritis (OA) mainly affects the articular cartilage covering the bones. In this thesis we investigated the relation between levels of inflammatory mediators, genes involved in their regulation and the disease status of OA. We investigated the role of genetic variation at the interleukin(IL)-1 gene cluster in the innate bio-availability of IL-1beta. A haplotype that associated to low innate bio-availability also associated to higher hand OA scores. Although this is counterintuitive with respect to the generally accepted hypothesis that a pro-inflammatory status is detrimental to the cartilage it underlines a complex relationship between inflammation and OA. For the C-reactive protein we identified a haplotype associated to high CRP levels as well as to severe hand OA, which is more in line with expected directions of associations. Analysis of baseline cytokine and chemokine levels indicated that chemokine levels associated to hand OA scores, again with low levels associated to high OA scores. In a follow up functional genomic analysis of a previously identified OA susceptibility gene (DIO2) in our studies we show that the risk allele of this gene is transcribed at higher levels as compared to the non-risk allele. Furthermore, we showed increased DIO2 protein presence in OA affected cartilage. Show less
This thesis describes the long-term consequences of growth hormone and insulin-like growth factor I excess in patients cured from acromegaly for a mean duration of 17 years. Regarding the... Show moreThis thesis describes the long-term consequences of growth hormone and insulin-like growth factor I excess in patients cured from acromegaly for a mean duration of 17 years. Regarding the considerable prevalence of diverse morbidity in these patients, during the active phase of the disease but even more so after 17 years of disease cure, we suggest the screening of acromegalic patients on highly frequent comorbidities, such as osteoarthritis, vertebral fractures, colonic polyps, and colonic diverticulae. It is of great concern to recognize the long-term consequences of the disease in order to offer the patients adequate follow-up and multidisciplinary care. The aim should be to control the persisting complex morbidity as much as possible in order to prevent the patients from a further decrease in quality of life. The patients__ physician as well as the patient itself should be aware of the long-term consequences of acromegaly in order to eliminate surreal expectations concerning recovery of certain comorbidities. Show less
Het is nu gangbaar in de kliniek om aan de hand van een enkele biochemische component (een gen, eiwit of metaboliet) vast te stellen of iemand ziek is. Echter, met geavanceerde meettechnieken zijn... Show moreHet is nu gangbaar in de kliniek om aan de hand van een enkele biochemische component (een gen, eiwit of metaboliet) vast te stellen of iemand ziek is. Echter, met geavanceerde meettechnieken zijn we nu in staat zijn om tientallen tot zelfs honderden van deze componenten tegelijk te meten. Hierdoor krijgen onderzoekers een veel breder overzicht van wat er allemaal verandert tijdens een ziekte en kunnen er betere diagnostische tests worden ontwikkeld. Voor dit proefschrift heb ik mij verdiept in deze technieken en hun toepasbaarheid in artrose. Artrose is een veel voorkomende rheumatische aandoening waarvan de exacte oorzaak nog onduidelijk is. Ik heb vastgesteld dat er met name nog weinig bekend is over het aandeel van de afbraakproducten van eiwitten en van vetten. Ik heb de benodige meettechnieken opgezet om honderden van deze afbraaktproducten en vetten te kunnen meten. Hieruit bleek dat een onstekingsmediator zeer verhoogd is in artrose en dat de samenstelling van vetten in het bloed van artrose patienten anders is dan bij gezonde mensen. De vindingen van dit proefschrift geven de kracht van deze meettechnieken aan om bij te dragen tot verbeterde diagnostische tests. Show less
