The Association Between Childhood Trauma and Attachment Functioning in Patients With Personality Disorders.

Attachment (mal)functioning and a history of childhood trauma (CT) are both considered psychological determinants of personality disorders (PDs). Their interaction, however, remains largely uninvestigated. In this study, the authors assessed adult and childhood attachment style in a sample of patients with diverse PDs ( = 75) and determined the relation with both occurrence and severity of CT.

Predicting individual responses to pravastatin using a physiologically based kinetic model for plasma cholesterol concentrations.

We used a previously developed physiologically based kinetic (PBK) model to analyze the effect of individual variations in metabolism and transport of cholesterol on pravastatin response. The PBK model is based on kinetic expressions for 21 reactions that interconnect eight different body cholesterol pools including plasma HDL and non-HDL cholesterol. A pravastatin pharmacokinetic model was constructed and the simulated hepatic pravastatin concentration was used to modulate the reaction rate constant of hepatic free cholesterol synthesis in the PBK model.

p38 inhibition and not MK2 inhibition enhances the secretion of chemokines from TNF-α activated rheumatoid arthritis fibroblast-like synoviocytes.

Objectives: For many years the p38 MAP kinase (MAPK) has been a major anti-inflammatory target for the development of an oral therapy for rheumatoid arthritis (RA). However, disappointing results from Phase II clinical studies suggest that adaptations may occur, which allow escape from blockade of the p38 pathway. In this study we investigated whether p38 inhibition mediated JNK activation represents such an escape mechanism.

Nutritional systems biology modeling: from molecular mechanisms to physiology.

The use of computational modeling and simulation has increased in many biological fields, but despite their potential these techniques are only marginally applied in nutritional sciences. Nevertheless, recent applications of modeling have been instrumental in answering important nutritional questions from the cellular up to the physiological levels. Capturing the complexity of today's important nutritional research questions poses a challenge for modeling to become truly integrative in the consideration and interpretation of experimental data at widely differing scales of space and time.

Systems biology for battling rheumatoid arthritis: application of the Entelos PhysioLab platform.

A large-scale mathematical model, the Entelos Rheumatoid Arthritis (RA) PhysioLab platform, has been developed to describe the inflammatory and erosive processes in afflicted joints of people suffering from RA. The platform represents the life cycle of inflammatory cells, endothelium, synovial fibroblasts, and chondrocytes, as well as their products and interactions. The interplay between these processes culminates in clinically relevant measures for inflammation and erosion.