Interaction of low density lipoproteins with rat liver cells

The most marked conclusion is the establishment of the important role of non-parenchymal cells in the catabolism of the low density lipoproteins by the rat liver. Because the liver is responsible for 70-80% of the removal of LDL from blood this conclusion can be extended to total LDL turnover. The relatively important role of the non-parenchymal liver cells in LDL uptake might be due to the low interaction of rat hepatocytes with human LDL, both in vivo and in vitro. This is in contrast to results obtained with hepatocytes from pig (108) and rabbit (30, 109). The role of non-parenchymal cells from pig, rabbit or human liver in LDL catabolism is unknown at the moment. Beside the important role of the non-parenchymal cells in LDL catabolism, we also illustrate an important role of these cells in the uptake and degradation of the potentially atherogenic lipoproteins acetyl-LDL and lipoprotein{a). Just like acetyl-LDL and biologically modified LDL (110) 1 Lp( a) is taken up by the endothelial liver cells to a higher extent than LDL, probably due to its interaction with the acetyl-LDL receptor. The receptor-dependent uptake of acetyl-LDL and Lp(a) by the liver endothelial cells and LDL by the Kupffer cells can have important consequences for the cholesterol metabolism in liver, because specifically receptor-dependent uptake regulates cholesterol synthesis and esterification (30, 108, 111). The low temperature perfusion and cell isolation techniques have greatly improved the recoveries of the total liver-associated radioactivity in the isolated liver cell types. The applied method may be an important aid in future experiments on the role of parenchymal and non-parenchymal cells in lipoprotein catabolism, in which the consequence of the receptor-dependent and independent uptake of lipoproteins for cholesterol metabolism in the various liver cell types can be studied

A two-sphere model for bacteria swimming near solid surfaces

We present a simple model for bacteria like \emph{Escherichia coli} swimming near solid surfaces. It consists of two spheres of different radii connected by a dragless rod. The effect of the flagella is taken into account by imposing a force on the tail sphere and opposite torques exerted by the rod over the spheres. The hydrodynamic forces and torques on the spheres are computed by considering separately the interaction of a single sphere with the surface and with the flow produced by the other sphere. Numerically, we solve the linear system which contains the geometrical constraints and the force-free and torque-free conditions. The dynamics of this swimmer near a solid boundary is very rich, showing three different behaviors depending on the initial conditions: (1) swimming in circles in contact with the wall, (2) swimming in circles at a finite distance from the wall, and (3) swimming away from it. Furthermore, the order of magnitude of the radius of curvature for the circular motion is in the range $8-50\,\mu$m, close to values observed experimentally.Comment: 10 pages, 4 figure

The Development of Practice Recommendations for Drug-Disease Interactions by Literature Review and Expert Opinion

Background Drug-disease interactions negatively affect the benefit/risk ratio of drugs for specific populations. In these conditions drugs should be avoided, adjusted, or accompanied by extra monitoring. The motivation for many drug-disease interactions in the Summary of Product Characteristics (SmPC) is sometimes insufficiently supported by (accessible) evidence. As a consequence the translation of SmPC to clinical practice may lead to non-specific recommendations. For the translation of this information to the real world, it is necessary to evaluate the available knowledge about drug-disease interactions, and to formulate specific recommendations for prescribers and pharmacists. The aim of this paper is to describe a standardized method how to develop practice recommendations for drug-disease interactions by literature review and expert opinion. Methods The development of recommendations for drug-disease interactions will follow a six-step plan involving a multidisciplinary expert panel (1). The scope of the drug-disease interaction will be specified by defining the disease and by describing relevant effects of this drug-disease interaction. Drugs possibly involved in this drug-disease interaction are selected by checking the official product information, literature, and expert opinion (2). Evidence will be collected from the official product information, guidelines, handbooks, and primary literature (3). Study characteristics and outcomes will be evaluated and presented in standardized reports, including preliminary conclusions on the clinical relevance and practice recommendations (4). The multidisciplinary expert panel will discuss the reports and will either adopt or adjust the conclusions (5). Practice recommendations will be integrated in clinical decision support systems and published (6). The results of the evaluated drug-disease interactions will remain up-to-date by screening new risk information, periodic literature review, and (re)assessments initiated by health care providers. Actionable Recommendations The practice recommendations will result in advices for specific DDSI. The content and considerations of these DDSIs will be published and implemented in all Clinical Decision Support Systems in the Netherlands. Discussion The recommendations result in professional guidance in the context of individual patient care. The professional will be supported in the decision making in concerning pharmacotherapy for the treatment of a medical problem, and the clinical risks of the proposed medication in combination with specific diseases

The Development of Practice Recommendations for Drug-Disease Interactions by Literature Review and Expert Opinion

Background: Drug-disease interactions negatively affect the benefit/risk ratio of drugs for specific populations. In these conditions drugs should be avoided, adjusted, or accompanied by extra monitoring. The motivation for many drug-disease interactions in the Summary of Product Characteristics (SmPC) is sometimes insufficiently supported by (accessible) evidence. As a consequence the translation of SmPC to clinical practice may lead to non-specific recommendations. For the translation of this information to the real world, it is necessary to evaluate the available knowledge about drug-disease interactions, and to formulate specific recommendations for prescribers and pharmacists. The aim of this paper is to describe a standardized method how to develop practice recommendations for drug-disease interactions by literature review and expert opinion. Methods: The development of recommendations for drug-disease interactions will follow a six-step plan involving a multidisciplinary expert panel (1). The scope of the drug-disease interaction will be specified by defining the disease and by describing relevant effects of this drug-disease interaction. Drugs possibly involved in this drug-disease interaction are selected by checking the official product information, literature, and expert opinion (2). Evidence will be collected from the official product information, guidelines, handbooks, and primary literature (3). Study characteristics and outcomes will be evaluated and presented in standardized reports, including preliminary conclusions on the clinical relevance and practice recommendations (4). The multidisciplinary expert panel will discuss the reports and will either adopt or adjust the conclusions (5). Practice recommendations will be integrated in clinical decision support systems and published (6). The results of the evaluated drug-disease interactions will remain up-to-date by screening new risk information, periodic literature review, and (re)assessments initiated by health care providers. Actionable Recommendations: The practice recommendations will result in advices for specific DDSI. The content and considerations of these DDSIs will be published and implemented in all Clinical Decision Support Systems in the Netherlands. Discussion: The recommendations result in professional guidance in the context of individual patient care. The professional will be supported in the decision making in concerning pharmacotherapy for the treatment of a medical problem, and the clinical risks of the proposed medication in combination with specific diseases

Standard set of health outcome measures for older persons

Background: The International Consortium for Health Outcomes Measurement (ICHOM) was founded in 2012 to propose consensus-based measurement tools and documentation for different conditions and populations.This article describes how the ICHOM Older Person Working Group followed a consensus-driven modified Delphi technique to develop multiple global outcome measures in older persons. The standard set of outcome measures developed by this group will support the ability of healthcare systems to improve their care pathways and quality of care. An additional benefit will be the opportunity to compare variations in outcomes which encourages and supports learning between different health care systems that drives quality improvement. These outcome measures were not developed for use in research. They are aimed at non researchers in healthcare provision and those who pay for these services. Methods: A modified Delphi technique utilising a value based healthcare framework was applied by an international panel to arrive at consensus decisions.To inform the panel meetings, information was sought from literature reviews, longitudinal ageing surveys and a focus group. Results: The outcome measures developed and recommended were participation in decision making, autonomy and control, mood and emotional health, loneliness and isolation, pain, activities of daily living, frailty, time spent in hospital, overall survival, carer burden, polypharmacy, falls and place of death mapped to a three tier value based healthcare framework. Conclusions: The first global health standard set of outcome measures in older persons has been developed to enable health care systems improve the quality of care provided to older persons

Assessment of Visual Association Memory in Low-Educated, Non-Western Immigrants with the Modified Visual Association Test

Background: Neuropsychological tests are influenced by culture, language, level of education, and literacy, but there are few cognitive tests of which the applicability in ethnic minority populations has been studied. Objectives: The aim of this study was to assess the reliability and validity of the Visual Association Test (VAT), a test of visual association memory, in a non-Western, low-educated memory clinic population. Additionally, a modified version of the VAT using colored photographs instead of line drawings was studied (mVAT). Method: Both the original VAT and the mVAT were administered to non-Western immigrants (n = 73) from 2 multicultural memory clinics in Rotterdam, The Netherlands, and a control sample of non-demented Turkish elderly (n = 14) with low education levels (32 and 29% illiterate, respectively). Results: Both the VAT and the mVAT were able to discriminate persons with and without dementia (area under the curve: VAT, 0.77-0.88; mVAT, 0.85-0.95). The mVAT had more homogeneous item difficulty levels than the VAT. Administration of parallel versions of the VAT and the mVAT within the same person revealed higher scores on the mVAT (Z = -3.35, p = 0.001). Conclusions: The mVAT is a reliable and valid measure of memory in non-Western immigrants. Clinicians and researchers should be aware that the memory performance of immigrants may be systematically underestimated when using tests with black-and-white line drawings, such as the original VAT