Long-term monounsaturated fatty acid diets reduce platelet aggregation in healthy young subjects

The aim of the present study was to compare the response of a range of atherogenic and thrombogenic risk markers to two dietary levels of saturated fatty acid (SFA) substitution with monounsaturated fatty acids (MUFA) in students living in a university hall of residence. Although the benefits of such diets have been reported for plasma lipoproteins in high-risk groups, more needs to be known about effects of more modest SFA-MUFA substitutions over the long term and in young healthy adults. In a parallel design over 16 weeks, fifty-one healthy young subjects were randomised to one of two diets: (1) a moderate-MUFA diet in which 16 g dietary SFA/100 g total fatty acids were substituted with MUFA (n 25); (2) a high-MUFA diet in which 33 g dietary SFA/100 g total fatty acids were substituted with MUFA (n 26). All subjects followed an 8-week run-in diet (reference diet), with a fatty acid composition close to the UK average values. There were no differences in plasma lipid responses between the two diets over 16 weeks of the study with similar reductions in total cholesterol (P<0.001) and LDL-cholesterol (P<0.01) in both groups; a small but significant reduction in HDL-cholesterol was also observed in both groups (P<0.01). Platelet responses to ADP (P<0.01) and arachidonic acid (P<0.05) differed with time on the two diets; at 16 weeks, platelet aggregatory response to ADP was significantly lower on the high-MUFA than the moderate-MUFA (P<0.01) diet; ADP responses were also significantly lower within this group at 8 (P< 0.05) and 16 (P< 0.01) weeks compared with baseline. There were no differences in fasting factor VII activity (factors VIII and VIIag), fibrinogen concentration or tissue-type plasminogen activator activity between the diets. There were no differences in postprandial factor VIII responses to a standard meal (area under the curve) between the diets after 16 weeks, but postprandial factor VIII response was lower than on the high-MUFA diet compared with baseline (P<0.01). In conclusion, a high-MUFA diet sustains potentially beneficial effects on platelet aggregation and postprandial activation of factor VII. Moderate or high substitution of MUFA for SFA achieves similar reductions in fasting blood lipids in young healthy subjects.

Sulfation of genistein alters its antioxidant properties and its effect on platelet aggregation and monocyte and endothelial function

Soy isoflavones have been extensively studied because of their possible benefits to human health. Genistein, the major isoflavone aglycone, has received most attention; however, it undergoes extensive metabolism (e.g. conjugation with sulfuric acid) in the gut and liver, which may affect its biological proper-ties. This study investigated the antioxidant activity and free radical-scavenging properties of genistein, genistein-4'-sulfate and genistein-4'-7-disulfate as well as their effect on platelet aggregation and monocyte and endothelial function. Electron spin resonance spectroscopy (ESR) and spin trapping data and other standard antioxidant assays indicated that genistein is a relatively weak antioxidant compared to quercetin and that its sulfated metabolites are even less effective. Furthermore, genistein-4'-sulfate was less potent than genistem, and genistein-4'-7-disulfate even less potent, at inhibiting collagen-induced platelet aggregation, nitric oxide (NO) production by macrophages, and secretion by primary human endothelial cells of monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1). The current data suggest that sulfation of genistein, with the associated loss of hydroxyl groups, decreases its antioxidant activity and its effect on platelet aggregation, inflammation, cell adhesion and chemotaxis. (C) 2004 Elsevier B.V All rights reserved.

Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in humans

Background: Quercetin, a flavonoid present in the human diet, which is found in high levels in onions, apples, tea and wine, has been shown previously to inhibit platelet aggregation and signaling in vitro. Consequently, it has been proposed that quercetin may contribute to the protective effects against cardiovascular disease of a diet rich in fruit and vegetables. Objectives: A pilot human dietary intervention study was designed to investigate the relationship between the ingestion of dietary quercetin and platelet function. Methods: Human subjects ingested either 150 mg or 300 mg quercetin-4'-O-beta-D-glucoside Supplement to determine the systemic availability of quercetin. Platelets were isolated from subjects to analyse collagen-stimulated cell signaling and aggregation. Results: Plasma quercetin concentrations peaked at 4.66 mum (+/-0.77) and 9.72mum (+/-1.38) 30min after ingestion of 150-mg and 300-mg doses of quercefin-4'-O-beta-D-glucoside, respectively, demonstrating that quercetin was bioavailable, with plasma concentrations attained in the range known to affect platelet function in vitro. Platelet aggregation was inhibited 30 and 120 min after ingestion of both doses of quercetin-4'-O-beta-D-glucoside. Correspondingly, collagen-stimulated tyrosine phosphorylation of total platelet proteins was inhibited. This was accorripanied by reduced tyrosine phosphorylation of the tyrosine kinase Syk and phospholipase Cgamma2, components of the platelet glycoprotein VI collagen receptor signaling pathway. Conclusions: This study provides new evidence of the relatively high systemic availability of quercetin in the form of quercetin-4'-O-beta-D-glucoside by supplementation, and implicates quercetin as a dietary inhibitor of platelet cell signaling and thrombus formation.

Effect of genistein and daidzein on platelet aggregation and monocyte and endothelial function

There has been much recent interest in the cardiovascular benefits of dietary isoflavones. The aim of the present in vitro studies was to investigate potential anti-thrombogenic and anti-atherogenic effects of the isoflavones genistein and daidzein in platelets, macrophages and endothelial cells. Pre-treatment with either isoflavone inhibited collagen-induced platelet aggregation in a dose-dependent manner. In a macrophage cell line (RAW 264-7) activated with interferon gamma plus lipopolysaccharide, both isoflavones were found to inhibit NO production and tumour necrosis factor alpha (TNF-alpha) secretion dose-dependently, but they did not affect mRNA levels for inducible nitric oxide synthase and cyclo-oxygenase-2. Both isoflavones also dose-dependently decreased monocyte chemoattractant protein-1 secretion induced by TNF-alpha in human umbilical vein endothelial cells. Compared with daidzein, genistein exerted greater inhibitory effects for all parameters studied. The present data contributes to our knowledge on the molecular mechanisms by which isoflavones may protect against coronary artery disease. Further studies are required to determine whether the effects of isoflavones observed in the current in vitro studies are relevant to the aetiology of coronary artery disease in vivo.

Workflow-oriented collaborative grid portals

The paper presents how workflow-oriented, single-user Grid portals could be extended to meet the requirements of users with collaborative needs. Through collaborative Grid portals different research and engineering teams would be able to share knowledge and resources. At the same time the workflow concept assures that the shared knowledge and computational capacity is aggregated to achieve the high-level goals of the group. The paper discusses the different issues collaborative support requires from Grid portal environments during the different phases of the workflow-oriented development work. While in the design period the most important task of the portal is to provide consistent and fault tolerant data management, during the workflow execution it must act upon the security framework its back-end Grids are built on.

Oriented vehicles travelling in spherical space

This paper tackles the path planning problem for oriented vehicles travelling in the non-Euclidean 3-Dimensional space; spherical space S3. For such problem, the orientation of the vehicle is naturally represented by orthonormal frame bundle; the rotation group SO(4). Orthonormal frame bundles of space forms coincide with their isometry groups and therefore the focus shifts to control systems defined on Lie groups. The oriented vehicles, in this case, are constrained to travel at constant speed in a forward direction and their angular velocities directly controlled. In this paper we identify controls that induce steady motions of these oriented vehicles and yield closed form parametric expressions for these motions. The paths these vehicles trace are defined explicitly in terms of the controls and therefore invariant with respect to the coordinate system used to describe the motion.

Toward construction of an inexpensive brain computer interface for goal oriented applications

The paper describes the implementation of an offline, low-cost Brain Computer Interface (BCI) alternative to more expensive commercial models. Using inexpensive general purpose clinical EEG acquisition hardware (Truscan32, Deymed Diagnostic) as the base unit, a synchronisation module was constructed to allow the EEG hardware to be operated precisely in time to allow for recording of automatically time stamped EEG signals. The synchronising module allows the EEG recordings to be aligned in stimulus time locked fashion for further processing by the classifier to establish the class of the stimulus, sample by sample. This allows for the acquisition of signals from the subject’s brain for the goal oriented BCI application based on the oddball paradigm. An appropriate graphical user interface (GUI) was constructed and implemented as the method to elicit the required responses (in this case Event Related Potentials or ERPs) from the subject.

Managing groups of files in a rule oriented data management system (iRODS)

The iRODS system, created by the San Diego Supercomputing Centre, is a rule oriented data management system that allows the user to create sets of rules to define how the data is to be managed. Each rule corresponds to a particular action or operation (such as checksumming a file) and the system is flexible enough to allow the user to create new rules for new types of operations. The iRODS system can interface to any storage system (provided an iRODS driver is built for that system) and relies on its’ metadata catalogue to provide a virtual file-system that can handle files of any size and type. However, some storage systems (such as tape systems) do not handle small files efficiently and prefer small files to be packaged up (or “bundled”) into larger units. We have developed a system that can bundle small data files of any type into larger units - mounted collections. The system can create collection families and contains its’ own extensible metadata, including metadata on which family the collection belongs to. The mounted collection system can work standalone and is being incorporated into the iRODS system to enhance the systems flexibility to handle small files. In this paper we describe the motivation for creating a mounted collection system, its’ architecture and how it has been incorporated into the iRODS system. We describe different technologies used to create the mounted collection system and provide some performance numbers.

An exploratory study of the effect of aspect-oriented programming on maintainability

In this paper we describe an exploratory assessment of the effect of aspect-oriented programming on software maintainability. An experiment was conducted in which 11 software professionals were asked to carry out maintenance tasks on one of two programs. The first program was written in Java and the second in AspectJ. Both programs implement a shopping system according to the same set of requirements. A number of statistical hypotheses were tested. The results did seem to suggest a slight advantage for the subjects using the object-oriented system since in general it took the subjects less time to answer the questions on this system. Also, both systems appeared to be equally difficult to modify. However, the results did not show a statistically significant influence of aspect-oriented programming at the 5% level. We are aware that the results of this single small study cannot be generalized. We conclude that more empirical research is necessary in this area to identify the benefits of aspect-oriented programming and we hope that this paper will encourage such research.