Ontwikkelingen in de diagnostiek en behandeling van leukemie bij kinderen met downsyndroom = Developments in diagnosis and treatment of leukemia in children with Down syndrome

Children with Down syndrome (DS) have an increased risk for developing both acute myeloid as well as acute lymphoblastic leukemia. These leukemias differ in clinical characteristics and biology compared to leukemias in non-DS children. Moreover, children with DS have an increased risk of side-effects from cytostatic therapy, which complicates...

Erosive arthritis in a patient with pycnodysostosis: An experiment of nature

Objective. The excellent poster painter Henri de Toulouse-Lautrec is the most famous patient with cathepsin K-deficient pycnodysostosis. Cathepsin K is believed to play a major role in osteoclast-driven bone resorption. In this study we explored the role of cathepsin K in bone resorption in a patient with a cathepsin K mutation causing...

Leflunomide and methotrexate reduce levels of activated matrix metalloproteinases in complexes with α2 macroglobulin in serum of rheumatoid arthritis patients

Objective: To analyse the effects of leflunomide and methotrexate treatment on matrix metalloproteinase (MMP) activity levels in a2 macroglobulin/MMP (α2M/MMP) complexes in the systemic circulation of rheumatoid arthritis (RA) patients. Methods: A total of 102 RA patients from a prospective, double-blind, randomised clinical trial comparing...

Prediction of in vivo embryotoxic effect levels with a combination of in vitro studies and PBPK modelling

The new EU legislations for chemicals (Registration, Evaluation and Authorization of Chemicals, REACH) and cosmetics (Seventh Amendment) stimulate the acceptance of in vitro and in silico approaches to test chemicals for their potential to cause reproductive effects. In the current study seven compounds with known in vivo developmental effects...

Markers for Type II Collagen Breakdown Predict the Effect of Disease-Modifying Treatment on Long-Term Radiographic Progression in Patients with Rheumatoid Arthritis

Objective. To investigate in a randomized clinical trial setting with an aggressive combination-therapy arm and a mild-monotherapy arm, whether therapy-induced changes in urinary C-terminal crosslinking telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) predict 5-year radiographic progression in patients with rheumatoid...

Bone turnover, joint damage and bone mineral density in early rheumatoid arthritis treated with combination therapy including high-dose prednisolone

Objectives. Exploration of bone metabolism changes at different levels of disease activity, both with and without oral corticosteroid therapy, and prediction of changes in joint damage and bone density from the observed changes in markers of bone turnover. Methods. Data analysis from a randomized clinical trial with 155 rheumatoid arthritis (RA)...

The antiinflammatory drug sulfasalazine inhibits tumor necrosis factor alpha expression in macrophages by inducing apoptosis

Objective. Sulfasalazine (SSZ) is a commonly used drug in the treatment of inflammatory diseases such as rheumatoid arthritis and Crohn's disease. In both diseases, the proinflammatory cytokine tumor necrosis factor α (TNFα) plays a prominent role. In these studies, we investigated the mechanism by which SSZ inhibits TNFα expression in...

Transport of glutathione A conjugates by the multifrug resistance protein 1

The human multidrug resistance protein MRP1 mediates transport of organic substrates conjugated to glutathione, glucuronide, or sulfate. The naturally occurring prostaglandins A1 and A2 can form two diastereomeric glutathione S-conjugates, and it has been speculated that these might be substrates for MRP1. Here we present evidence that polarized...

Modification of the early and late delayed radiation response of the rat spinal cord by chemotherapeutic agents

Chemicals/CAS: cytarabine, 147-94-4, 69-74-9; methotrexate, 15475-56-6, 59-05-2, 7413-34-5

Intra arterial infusion with methotrexate in the rat

Chemicals/CAS: folinate calcium, 1492-18-8, 51057-63-7; folinic acid, 58-05-9, 68538-85-2; methotrexate, 15475-56-6, 59-05-2, 7413-34-5; Leucovorin, 58-05-9; Methotrexate, 59-05-2