Objective. To investigate individual variations of platelet inhibition after clopidogrel-loading doses. Setting. Department of Cardiology, Linköping University Hospital, Linköping, Sweden. Subjects. Individuals with stable angina pectoris (n ¼ 18) subject to percutaneous coronary interventions (PCI) and subsequent stenting were investigated. Methods and experimental protocol. A 300-mg clopidogrel loading dose was administrated immediately after stenting (day 1) followed by an additional 75 mg clopidogrel after 24 h (day 2). The ADP-evoked platelet fibrinogen binding was analysed to estimate platelet reactivity immediately before angiography and on day 2. A flow cytometry technique was used with two ADP solutions (final concentrations 0.6 and 1.7 lmol L )1 ) employed as platelet activating agents. Soluble P-selectin was used as a marker of platelet activity.Results. When using 1.7 lmol L )1 ADP to activate platelets four individuals had a strong inhibition (i.e. platelet reactivity <10% of the day 1-value day 2).In contrast, five patients demonstrated a weak inhibition (i.e. platelet reactivity >60% of the day 1-value day 2). Similar results were obtained when using 0.6 lmol L )1 ADP as a platelet-activating agent. Clopidogrel, however, fails to suppress platelet activity as estimated from soluble P-selectin.Conclusions. Clopidogrel evoked platelet inhibition exhibits a considerable individual heterogeneity. Some individuals only had weak responses whereas others displayed strong platelet inhibition. The present flow cytometry technique appears suitable for identifying patients with abnormal reactions after clopidogrel exposure.

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The present work demonstrates considerable platelet alterations in pre-eclampsia. We failed to show granulocyte involvement in the pathogenesis of the disease. Severe pre-eclampsia is related to elevated mean platelet volumes. The latter parameter is associated with disturbed density distribution. It appears possible to estimate disease severity from measurements of platelet density and volume.

Summary Objective: The present study investigates platelet density and mean platelet volume (MPV) in active inflammatory bowel disease (IBD). Experimental protocol: 27 patients with IBD (18 ulcerative colitis and 9 Crohn’s disease) were compared to 12 healthy volunteers. 18 subjects had active disease. Platelet counts and mean platelet volume (MPV) were determined. Thereafter, platelets were separated according to density on a linear preformed Percoll gradient. A computerized device was employed for scanning transmission variations and thus the platelet distribution in the gradient and the platelet peak were identified.

Background: Biomarkers are central to current research on molecular mechanisms underlying Alzheimer’s disease (AD). Their further development is of paramount importance for understanding pathophysiological processes that eventually lead to disease onset. Biomarkers are also crucial for early disease detection, before clinical manifestation, and for development of new disease modifying therapies. Objective: The overall aim of this work is to develop a minimally invasive method for fast, ultra-sensitive and cost-effective detection of structurally modified peptide/protein self-assemblies in the peripheral blood and in other biological fluids. Specifically, we focus here on using this method to detect structured amyloidogenic oligomeric aggregates in the blood serum of apparently healthy individuals and patients in early AD stage, and measure their concentration and size. Methods: Time-resolved detection of Thioflavin T (ThT) fluorescence intensity fluctuations in a sub-femtoliter observation volume element was used to identify in blood serum ThT-active structured amyloidogenic oligomeric aggregates, hereafter called nanoplaques, and measure with single-particle sensitivity their concentration and size. Results: The concentration and size of structured amyloidogenic nanoplaques are significantly higher in the blood serum of individuals diagnosed with AD than in control subjects. Conclusion: A new method with the ultimate, single-particle sensitivity was successfully developed. The proposed approach neither relies on the use of immune-based probes, nor on the use of radiotracers, signal-amplification or protein separation techniques, and provides a minimally invasive test for fast and cost-effective early determination of structurally modified peptides/proteins in the peripheral blood, as shown here, but also in other biological fluids.