Kidney Pathology Precedes and Predicts the Pathological Cascade of Cerebrovascular Lesions in Stroke Prone Rats

INTRODUCTION: Human cerebral small vessel disease (CSVD) has been hypothesized to be an age-dependent disease accompanied by similar vascular changes in other organs. SHRSP feature numerous vascular risk factors and may be a valid model of some aspects of human CSVD. Here we compare renal histopathological changes with the brain pathology of spontaneously hypertensive stroke-prone rats (SHRSP). MATERIAL AND METHODS: We histologically investigated the brains and kidneys of 61 SHRSP at different stages of age (12 to 44 weeks). The brain pathology (aggregated erythrocytes in capillaries and arterioles, microbleeds, microthromboses) and the kidney pathology (aggregated erythrocytes within peritubular capillaries, tubular protein cylinders, glomerulosclerosis) were quantified separately. The prediction of the brain pathology by the kidney pathology was assessed by creating ROC-curves integrating the degree of kidney pathology and age of SHRSP. RESULTS: Both, brain and kidney pathology, show an age-dependency and proceed in definite stages whereas an aggregation of erythrocytes in capillaries and arterioles, we parsimoniously interpreted as stases, represent the initial finding in both organs. Thus, early renal tubulointerstitial damage characterized by rather few intravasal erythrocyte aggregations and tubular protein cylinders predicts the initial step of SHRSPs' cerebral vascular pathology marked by accumulated erythrocytes. The combined increase of intravasal erythrocyte aggregations and protein cylinders accompanied by glomerulosclerosis and thrombotic renal microangiopathy in kidneys of older SHRSP predicts the final stages of SHRSPs' cerebrovascular lesions marked by microbleeds and thrombotic infarcts. CONCLUSION: Our results illustrate a close association between structural brain and kidney pathology and support the concept of small vessel disease to be an age-dependent systemic pathology. Further, an improved joined nephrologic and neurologic diagnostic may help to identify patients with CSVD at an early stage

The Third Workshop on Behaviour Modelling - Foundations and Applications

Recent trends in software system development point to the growing importance of behaviour modelling. These trends are: -The growing role of business process management and workflow; - The growing importance of Service-Orientation as an architectural principle, with consequent emphasis on well defined interaction between software components; - The importance of interfaces, contracts and service level agreements in defining and managing of behaviour integration both within and across organizational boundaries; - The growing variety of business intelligence applications and their increasing complex behavioural requirements. To meet the challenges presented by these trends we must be able to determine which behaviour modelling techniques are applicable to a given situation, and be able to use multiple techniques in combination. This requires suitable and simple compositional semantics so that the various models used to describe the behaviour of a complex system can be put together. Behaviour modelling attracts more attention as the research community understands that behaviour modelling concepts are different from programming concepts and can be used to create programming languages of the next generation

Aspect-Oriented Model Development at Different Levels of Abstraction

The last decade has seen the development of diverse aspect- oriented modeling (AOM) approaches. This paper presents eight different AOM approaches that produce models at different level of abstraction. The approaches are different with respect to the phases of the development lifecycle they target, and the support they provide for model composition and verification. The approaches are illustrated by models of the same concern from a case study to enable comparing of their expressive means. Understanding common elements and differences of approaches clarifies the role of aspect-orientation in the software development process

Pharmacokinetics of drugs in cachectic patients:a systematic review

Cachexia is a weight-loss process caused by an underlying chronic disease such as cancer, chronic heart failure, chronic obstructive pulmonary disease, or rheumatoid arthritis. It leads to changes in body structure and function that may influence the pharmacokinetics of drugs. Changes in gut function and decreased subcutaneous tissue may influence the absorption of orally and transdermally applied drugs. Altered body composition and plasma protein concentration may affect drug distribution. Changes in the expression and function of metabolic enzymes could influence the metabolism of drugs, and their renal excretion could be affected by possible reduction in kidney function. Because no general guidelines exist for drug dose adjustments in cachectic patients, we conducted a systematic search to identify articles that investigated the pharmacokinetics of drugs in cachectic patients