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Biomedical subjects

F Misselwitz

Publications and source records attributed to F Misselwitz.

26 records · Page 2Linked to original sources
PubMed1988

Individually controlled acetylsalicyclic acid (ASA) in the long-term treatment of patients with arteriosclerosis.

A simple method to measure the biological effect of ASA based on the determination of the desaggregation rate (DR) of platelet aggregation induced by ADP is described. DR correlates with the inhibition of the production of malondialdehyde (MDA) by platelets (r = 0.66, P less than 0.001). Therefore, the DR was used for laboratory monitoring of the ASA effect. Here we report on a study including 41 patients with peripheral arterial disease and/or coronary heart disease before treatment and after receiving ASA in an individually controlled dosage regimen. Before treatment we found an increased level of MDA, 150-200% compared with healthy volunteers (n = 16). Extremely different doses of ASA were required to normalize initially elevated MDA-levels in patients. This normalization of MDA was found to correspond to a DR of at least 50% (in comparison to 0-13% without treatment). When judging the ASA-dose individually from the 50%-DR we demonstrated that there were no differences of the levels of cyclooxygenase- and lipoxygenase-derived eicosanoids between healthy volunteers (n = 16) and arteriosclerotic patients receiving 100-250 mg ASA/d (n = 18), 500 mg ASA/d (n = 17), or 750-1500 mg ASA/d (n = 6).

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Effect of metabolic inhibitors on platelet attachment, spreading and aggregation on collagen-coated surfaces.

The interaction of human gel-filtered platelets (GFP) with surfaces coated with fibrillar calf skin collagen (CSC) or monomeric human type I, III, IV, and V collagen (CI, CIII, CIV, CV) includes both energy dependent and independent stages. Incubation of platelets with a collagen-coated surface at 4 degrees C versus 37 degrees C reduces only shape change and the spreading response of adhering platelets, but does not affect the initial attachment. Additionally, the energy dependence was evident from the reduction of platelet spreading and platelet aggregate formation in the presence of 2-Deoxy-D-glucose (2DG). Antimycin A (AMA), Oligomycin (OM), or 2,4-Dinitrophenol (DNP) did not abolish the adhesion-induced platelet activation, indicating that the energy is supplied by glycolysis rather than by oxydative phosphorylation. In contrast, neither inhibition of glycolysis, nor inhibition of the respiratory chain did affect the initial attachment of nonactivated platelets to the collagen-coated surface. The present data suggest (i) that during the interaction of platelets with collagenous substrates there exists an initial energy independent attachment stage, and (ii) that the following stages of adhesion-induced platelet activation require metabolic energy supported mainly by anaerobic glycolysis.

2,4-Dinitrophenol↗
PubMed1987

Binding of human monomeric type I collagen to platelets.

Interaction of platelets with subendothelial collagen is important in primary hemostasis and thrombosis. Although activation of platelets by collagen polymers has been widely investigated, only insufficient data are available concerning the binding of genetically distinct collagen types in their triple helical (monomeric) form to platelets. We report on the binding of 125I-labeled human type I collagen to platelets. The binding assay was performed at 20 degrees C in the presence of arginine in order to prevent polymerization of the collagen monomers. The binding of monomeric 125I-labeled human type I collagen is dose- and time-dependent, saturable and specific, since it is competitively inhibited by unlabeled type I collagen, but not by unlabeled human type V collagen. Scatchard analysis reveals a class of specific high affinity binding sites with a Kd of 2.5 X 10(-8) M. These results suggest that platelets interact with type I collagen through specific binding sites, and that there are various different binding sites on the platelet membrane for the genetically distinct collagen types.

Binding Sites↗
PubMed1987

Influence of thromboxane receptor-antagonists on the interaction of platelets with solid-phase immobilized human collagen.

The interaction of blood platelets with surfaces coated with human type I, III, IV, and V collagen (CI, CIII, CIV, and CV) has been studied. Using scanning electron microscopy it was demonstrated that the reactivity of the collagen substrates for platelets varies widely. In contrast to CV and CIV, on surfaces coated with CI and CIII, along with spreading, the formation of thrombi-like platelet aggregates occurs. Previously, it was demonstrated that this thrombogenesis in vitro correlates well with the synthesis of platelet prostanoids, and is sensitive to inhibitors of TXA2-synthesis. Therefore, we have investigated the influence of the TXA2/PGH2 receptor-antagonists, 13-azaprostanoic acid (13-APA) and the BM 13.177 compound, on the formation of thrombi-like platelet aggregates on CI and CIII-coated surfaces. It was demonstrated that both 13-APA and BM 13.177 cause a dose-dependent inhibition of the thrombogenesis without any effect on the initiation of the thrombogenesis without any effect on the initial attachment and the spreading of platelets on collagen-coated surfaces. The obtained data suggest that (1) the formation of platelet aggregates on CI and CIII-coated surfaces is triggered by platelet prostanoids; (2) TXA2/PGH2 receptor-antagonists may be useful as antithrombotic drugs.

Blood Platelets↗
PubMed1984

Step-by-step analysis of adhesion of human platelets to a collagen-coated surface defect in initial attachment and spreading of platelets in von Willebrand's disease.

Adhesion of platelets from the platelet-rich plasma (PRP) of patients with von Willebrand's disease (vWD) and healthy donors has been studied in a simple model system - wells of multiwell tissue culture plates coated with fibrillar calf skin collagen (CSC). This model is characterized by: (i) the presence of only one constituent of the vessel wall connective tissue matrix (collagen), (ii) the absence of surface-bound aggregates and thrombi, (iii) absence of overlapping of neighbouring spread platelets. A morphometric quantitation of adhesion by scanning electron microscopy (SEM) has been carried out. It allows to subdivide this process into three stages: 1) initial attachment of unspread platelets to the substrate, 2) platelet spreading on the substrate, and 3) attachment of unspread platelets to the upper surface of spread platelets. It was established that the PRP of vWD patients, compared to that of healthy donors, is characterized by a decreased total adhesion of platelets to a CSC-coated surface, which is manifested in the impairment of both the initial attachment and subsequent spreading of platelets. Addition of platelet-free plasma from healthy donors to the vWD PRP completely restores platelet spreading on collagen but little affects the initial attachment. These experiments performed on isolated collagen preparations provide further evidence for the initial attachment and spreading of platelets on collagenous constituents of the subendothelium being factor VIII/von Willebrand factor (FVIII/vWF)-dependent. In contrast to the adhesion on the collagen substrate, the adhesion of platelets from vWD PRP to a foreign surface, polystyrene plastic of uncoated wells, is the same as that of the normal PRP and, thus, FVIII/vWF-independent.

Collagen↗
PubMed1984

[Thrombocyte adhesion and aggregation on surfaces coated with human type-I, -III, -IV and -V collagens].

Human collagens of type I, III, IV, and V (CI, CIII, CIV, and CV) can be localized in different anatomic structures of the vessel wall. To investigate the role of vascular collagenous components in mural thrombus formation, the authors studied platelet adhesion to the wells of Falcon culture plates coated with: a) monomeric CI, CIII, CIV, and CV; b) fibrillar CI and CIII, and c) amorphous CIV and CV. On monomeric and amorphous CV, only initial attachment takes place, i.e. platelets bind to the surface without subsequent spreading. Platelet adhesion on monomeric and amorphous CIV proceeds more actively: the total level of adhesion is substantially higher than on CV, with up to 75% of adherent platelets spread out and single unspread platelets from suspension attached to the upper surface of spread platelets. On monomeric and fibrillar CI/CIII, formation of large multi-layer (thrombi-like) aggregates, with spread platelets at the basis, takes place along with processes characteristic for adhesion on CIV/CV. On the contrary, only fibrillar but not monomeric CI and CIII induce platelet aggregation in suspension. The data suggest that the ability of CI and CIII to induce platelet aggregation is fully conditioned by the genetic type of collagen and requires a simultaneous multivalent platelet-collagen interaction, which can be achieved by surface immobilization of collagen or formation of fibrillar structures in suspension.

Blood Platelets↗
PubMed1984

Platelet prostanoids in interaction of platelets with collagen substrates. I. Activation of platelets by surfaces coated with different types of human collagen.

We have studied the interaction of human platelets with surfaces coated with human type I, III, IV, and V collagen (CI, CIII, CIV, and CV). It was established using scanning electron microscopy that the reactivity of the collagen substrates for platelets varies widely. On CV, only the initial attachment of platelets takes place; spreading actively goes on CIV while on CI and CIII, along with spreading, the formation of multilayer thrombi-like platelet aggregates occurs. The production of malondialdehyde induced by the interaction of platelets with CI and CIII substantially exceeds that stimulated by CIV and CV. Indomethacin practically completely inhibits the formation of thrombi-like aggregates but only by 25% inhibits platelet spreading. An ADP-scavenger creatine phosphate/creatine phosphokinase inhibits the formation of thrombi-like aggregates and platelet spreading by 25-30%. The obtained data demonstrate that: (i) the formation of thrombi-like aggregates on CI and CIII is mediated mainly by the synthesis of platelet prostanoids, and not by the ADP release; (ii) the spreading of platelets on CIV, CIII, and CI is only partially mediated by prostanoid synthesis and ADP release which suggests a participation of other mechanisms in this process.

Blood Platelets↗