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Biomedical subjects

W Lösche

Publications and source records attributed to W Lösche.

At least 37 records · Page 2Linked to original sources
PubMed1995

Factors that contribute to spontaneous platelet aggregation and streptokinase-induced aggregation in whole blood.

When whole blood is stirred there is a "spontaneous" platelet aggregation (SPA) which is presumed to be caused by proaggregatory factors released from platelets and other blood cells. Adding streptokinase (SK) to stirred whole blood frequently increases the rate and extent of the platelet aggregation that occurs; this is likely to be via immune complex formation between SK and natural anti-SK antibodies leading to increased release of pro-aggregatory factors. In this investigation we have examined the effects of several inhibitors and antagonists in an attempt to identify the proaggregatory factors that contribute to both SPA and SK-induced aggregation (SKA) and to evaluate different means of inhibiting both processes. The effects of the inhibitors/antagonists were determined in vitro after adding them to citrated whole blood obtained from healthy volunteers. Platelet aggregation was measured using a platelet counting technique. Inhibition of both SPA and SKA by apyrase and by FPL 66096 (a P2T receptor antagonist) demonstrated the involvement of ADP in both processes. Inhibition by chlorpromazine indicated that the most likely source of the ADP is red cells. The effects of sulotroban (a TXA2 antagonist) indicated involvement of TXA2 in SKA but not in SPA. The lack of effect of specific antagonists at S2, alpha 2 and PAF receptors suggested lack of involvement of serotonin, catecholamines and platelet-activating factor in either SPA or SKA. Both SPA and SKA were potently inhibited by low concentrations of iloprost (a PGI2 analogue), but a high concentration of SIN-1 (a NO donor) was much less effective.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1994

Generation of reactive oxygen species and activity of platelet-activating factor acetylhydrolase in human monocyte-derived macrophages.

Monocytes were prepared from healthy human volunteers and were allowed to differentiate into macrophages by adhesion to plastic surface and cultured over 7 days in presence of either 10% fetal calf serum (FCS), human control serum or serum from hyperlipaemic patients. Hyperlipaemic serum stimulated the differentiation (measured as an increase in cellular protein and DNA content) to a higher extent when compared to control serum and FCS. With all sera a marked increase of the cellular activity of the enzyme platelet-activating factor acetylhydrolase (PAF-AH) and a tremendous decrease in the capacity of cells to generate reactive oxygen species (ROS) was observed. After seven days of culture the increase in PAH-AH activity was about 19-fold with hyperlipaemic serum, 11-fold with control serum and 6-fold with FCS. During the same period of time ROS generation measured as zymosan-induced chemiluminescence decreased by about 98% and no significant differences between the three types of serum were found. The results indicate that the activity of PAF-AH and the capacity of ROS generation which are both assumed to play an important role in the oxidation of low-density lipoproteins (LDL) and thus in the development of atherosclerosis, change in opposite direction during the differentiation of blood monocytes into macrophages, and that hyperlipaemic serum stimulates PAF-AH activity but not ROS generation.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1993

The platelet glycoprotein IIb/IIIa complex is involved in the adhesion of activated platelets to leukocytes.

The adhesion of activated platelets to leukocytes (rosette formation) seems to be mediated by CD62 on platelets and its counter-receptor (CD15 or a sialic acid-containing glycoprotein) on polymorphonuclear leukocytes (PMNL). However, neither treatment of platelets with an anti-CD62 antibody or fucoidan nor treatment of PMNL with anti-CD15 antibody or neuraminidase are able to inhibit completely the adhesion. Therefore, we have studied the platelet GPIIb/IIIa complex (CD41a) for its involvement in the adhesion of activated platelets to PMNL. The following evidences point to a participation of CD41a in the adhesion of activated platelets to leukocytes: a) inhibition of adhesion by monoclonal antibodies (mab) raised toward CD41a, b) inhibition of adhesion by peptides such as RGDS and echistatin, c) inhibition of adhesion by dissociation of the CD41a complex with EGTA, and d) inhibition of rosette formation using platelets from a thrombasthenic patient which have almost no CD41a in the surface membrane but a normal expression of CD62. It is likely that fibrinogen is involved in the adhesion of platelets to PMNL via CD41a, since fibrinogen increases the rosette formation of ADP-stimulated platelets. Furthermore, the incubation of unstimulated platelets with fibrinogen and an antibody raised against glycoprotein IIIa which stimulates fibrinogen binding to the platelet surface results in an enlarged rosette formation.

Amino Acid Sequence↗
PubMed1992

Functional behaviour of mononuclear blood cells from patients with hypercholesterolemia.

Mononuclear cells were prepared from venous blood obtained from 20 patients with a newly diagnosed hypercholesterolemia and without clinical signs of vascular disease, and from 19 age and sex matched controls. Adhesiveness to plastic surface, phagocytic activity measured as ingestion of zymosan particles, and spontaneous motility of mononuclear cells from patients were significantly higher by 57%, 19% and 50%, respectively, when compared to controls. In controls chemotaxis induced by the chemotactic peptide FMLP was slightly higher than spontaneous motility measured in absence of FMLP, whereas in patients FMLP significantly inhibited cell motility by about 47%. With the exception of FMLP-induced chemotaxis the results indicate that mononuclear cells are hyperreactive in hypercholesterolemia.

Adult↗
PubMed1992

Ex vivo investigation of blood monocyte and platelet behaviour in pigs maintained on an atherogenic diet.

Domestic pigs aged 4 months were fed for 16 weeks an atherogenic diet rich in cholesterol and saturated fatty acid. The increase of plasma cholesterol and triacylglycerol levels was found to be accompanied by a significant increase in the number of blood monocytes and platelets when compared to control animals. Furthermore, the atherogenic diet produced a small but significant reduction in the blood monocyte phagocytic capacity and adhesion to plastic surface. No significant differences between both groups were found when spontaneous platelet aggregation in whole blood was studied. However, platelets from pigs fed the atherogenic diet had a smaller mean cell volume compared to controls. The results indicate than an atherogenic diet may affect blood monocytes and platelets in pigs.

Animals↗
PubMed1992

Defective function of blood granulocytes in patients with diabetes mellitus-associated marginal periodontitis.

In ten periodontitis patients suffering from type I diabetes mellitus, phagocytic activity, aggregation and chemiluminescence generation of blood granulocytes were determined. Compared to controls with clinically healthy periodontal conditions, the phagocytosis of zymosan particles and the aggregation response induced by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine were significantly decreased, whereas aggregation induced by the platelet-activating factor, a potent mediator of inflammation, was significantly enhanced.

Adult↗
PubMed1991

[Measurement of spontaneous platelet aggregation in citrated whole blood by application of the hematologic automatic Coulter S plus VI].

A method for measurement of the spontaneous platelet aggregation in citrated whole blood (SPAV) was tested using the Coulter Counter S plus VI and a simple mechanism for sample rotation. The underlying principle of the procedure consists in the sequential measurement of the decrease of free platelets in a specimen of citrated whole blood which ist rotated at 37 degrees C for 20 minutes. SPAV offers advantages compared to other methods for spontaneous aggregation in platelet rich plasma. First experiences about application of the SPAV-procedure are presented.

Autoanalysis↗
PubMed1990

Helenalin and 11 alpha,13-dihydrohelenalin, two constituents from Arnica montana L., inhibit human platelet function via thiol-dependent pathways.

This study investigates the effect on human platelet function of two sesquiterpene lactones from Arnica montana L., helenalin (H) and 11 alpha,13-dihydrohelenalin (DH). Both compounds inhibited collagen-induced platelet aggregation, thromboxane formation and 5-hydroxytryptamine secretion in a concentration-dependent manner at 3-300 microM. When arachidonic acid was used as stimulus, thromboxane formation remained unaffected despite of inhibition of platelet aggregation. Both H and DH reduced the number of acid-soluble sulfhydryl groups in platelets, by up to 78% at anti-aggregatory concentrations. Moreover, H- and DH-induced platelet inhibition could be prevented by the thiol containing amino acid cysteine. It is concluded that H and DH inhibit platelet function via interaction with platelet sulfhydryl groups, probably associated with reduced phospholipase A2 activity.

Arachidonic Acid↗
PubMed1990

Aggregation behaviour of blood granulocytes in patients with periodontal disease.

This behaviour was studied in 17 patients with severe marginal periodontitis and in 16 healthy controls. Aggregation induced by platelet-activating factor (PAF-acether), a potent mediator of inflammation, was significantly enhanced in the patients, whereas no significant difference was observed between patients and controls when aggregation was induced by the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP). When the patients were subdivided into categories of progressive adult periodontitis, juvenile or post-juvenile periodontitis, aggregation induced by PAF-acether was enhanced in all three subgroups. However, FMLP-induced aggregation was slightly increased only in progressive adult and post-juvenile periodontitis, but decreased in juvenile periodontitis.

Adolescent↗
PubMed1990

[The phagocytic activity of the blood neutrophilic granulocytes in patients with marginal periodontitis].

The ingestion of opsonized zymosan particles by neutrophil blood granulocytes and the chemiluminescence in samples of whole blood, induced by zymosan, Streptococcus mutans as well as phorbol myristate acetate, as a measure of the generation of reactive oxygene species were studied in patients with various forms of marginal periodontitis. Compared to a control group the phagocytic activity was found to be enhanced in progressive adult periodontitis and diminished in juvenile periodontitis whereas no differences to controls were found in chronic nonprogressive or postjuvenile periodontitis. With respect to the height of the chemiluminescence signals increased values were only measured in chronic nonprogressive periodontitis after stimulation by phorbol myristate acetate. The results indicate that impairment of blood granulocyte functions may be a pathogenetic factor for the development and the progression of marginal periodontitis.

Adolescent↗
PubMed1990

Influence of substances affecting cell sulfhydryl/disulfide status on adherence of human monocytes.

An in-vitro model is described for investigating the adherence of human monocytes. Mononuclear cells (MNC) isolated from peripheral blood were incubated in plastic multiwell cell culture plates. The adherence of monocytes was quantified on the basis of their DNA content. The cell adherence proceeds rapidly; after 30 min of incubation about 85% of maximum adherent cells were attached to the plastic surface. On testing the effects of various sulfhydryl-affecting substances on monocyte adherence we found that the thiol-oxidizing compound diamide (0.1-1 mmol/l) inhibited the adherence by about 60%. Incubation with an extract of the plant feverfew, which contains materials that neutralize cellular sulfhydryl groups, also diminished monocyte adherence. The soluble thiol 2-mercaptopropionylglycine, in a concentration range of 0.5 to 10 mmol/l, had no effect on adherence in this system. The results suggest that cellular sulfhydryl groups play an important role in the adherence of monocytes.

Cell Adhesion↗
PubMed1989

[Cellular chemiluminescence of activated phagocytes of whole blood].

Both, the phagocytic process and the activation of phagocytes with soluble stimuli are accompanied by increased production of reactive oxygen species (ROS). Chemiluminescence (CL) measurement is a simple and sensitive method for the detection of ROS generation. Phagocytes (mainly polymorphonuclear leukocytes, PMNL) were stimulated with soluble stimulus or via phagocytosis in diluted whole blood, and the generation of Luminol-enhanced CL was registered. The time dependence of CL, determined in whole blood, corresponds to the CL from isolated leukocytes. A relationship between peak CL and the number of leukocytes as well as of PMNL was observed. The specific CL, i.e. the CL response related to a defined PMNL number, increases with the age of investigated healthy individuals. No correlations were found between CL and the capacity of PMNL to ingest zymosan particles. Relations between CL and spontaneous platelet aggregation suggest, that reactivity of blood platelets may be a contributing factor to the kinetics of the CL signal in our test system. The inhibition of CL by the sulphydryl reagents diamide and fever few extract indicate the role of cellular sulphydryl groups for phagocyte function. Measurement of CL in whole blood is proved to be a simple assay for assessment of PMNL function and allows measurements in very small blood samples (greater than or equal to 10 ul).

Cell Separation↗
PubMed1989

N-(2-mercaptopropionyl)-glycine inhibits chemiluminescence and accelerates phagocytosis in human polymorphonuclear leukocytes.

Treatment of polymorphonuclear leukocytes with the soluble and cell penetrating thiol N-(2-mercaptopropionyl)-glycine (2-MPG) inhibits luminol-enhanced chemiluminescence induced by opsonized zymosan, which is believed to be a measure for the generation of reactive oxygen species, and accelerates the rate of phagocytosis measured as ingestion of zymosan particles. It is discussed that 2-MPG protects the phagocyting cells from oxidative damage by reactive oxygen species that are formed during particle ingestion.

Humans↗
PubMed1989

[The effect of high glucose concentrations on the osmotic and mechanical resistance of human erythrocytes].

Incubation of citrated or heparinized blood samples with 25 or 50 mmoles/l glucose for 1 hour at 37 degrees C results in a decrease in the osmotic and mechanical resistance of red blood cells as well as in an increase in the red blood cell volume measured as increase in haematocrit. Fructose, but not sorbitol or saccharose has effects on red blood cells that are similar to those of glucose. It is discussed that an uptake of glucose into red blood cells with subsequent water influx results in swelling and decreased stability of the cells.

Erythrocyte Volume↗