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Biomedical subjects

W Lösche

Publications and source records attributed to W Lösche.

At least 55 records · Page 3Linked to original sources

[The binding of blood plasma proteins and salivary proteins to hydroxyapatite columns and its effect on demineralization in an in vitro system].

Demineralization of hydroxyapatite (HAP) columns by acidic acetate buffer proceeds in two phases. In an initial phase which is characterized by the formation of pH gradient within the HAP sediment, calcium but no phosphate ions are eluted from the column. In the second phase when a low pH value has been established in the pellet calcium and phosphate are eluted in a ratio identical to that of the original HAP. The binding of human blood plasma proteins and saliva proteins to the HAP as well as the effect of the protein binding on HAP demineralization was investigated. The maximum binding capacity of HAP for the proteins of unstimulated mixed saliva is about four times lower than the binding of human serum albumin or blood plasma proteins. However, saliva proteins affect HAP demineralization more markedly than the other proteins. Whereas the pretreatment of HAP with human serum albumin does not alter the the demineralization process. binding of blood plasma proteins inhibits the initial phase of demineralization. Both phases of HAP demineralization are strongly inhibited when saliva proteins are bound to HAP. It is also shown that demineralization modifies the protein binding to HAP.

Blood Proteins↗

Inhibition of platelet behaviour by feverfew: a mechanism of action involving sulphydryl groups.

Extracts of feverfew inhibit platelet aggregation and the platelet release reaction. The active components are believed to be sesquiterpene lactones such as parthenolide. Evidence is presented that inhibition of platelet behaviour is via neutralization of sulphydryl groups either inside or outside the cell. The precise nature of the sulphydryl groups that are susceptible to feverfew and are involved in platelet aggregation and the release reaction have not yet been defined.

Arachidonic Acids↗

Methylene blue inhibits the arachidonic acid metabolism in human blood platelets.

When human blood platelets are incubated with methylene blue (MB) that oxidizes cellular NADPH, a marked inhibition of platelet aggregation and of the metabolism of arachidonic acid (AA) in both the cyclooxygenase and lipoxygenase pathway is found. The inhibition of aggregation and AA metabolism is prevented, at least partially, by the thiol-oxidizing agent diamide. The results indicate an involvement of the reduced coenzymes NADPH and glutathione (GSH) in the regulation of cyclooxygenase and lipoxygenase activity in platelets.

Arachidonic Acids↗

An extract of feverfew inhibits interactions of human platelets with collagen substrates.

The interaction of platelets with surfaces coated with collagens of type III (C III) or IV (C IV) has been studied by measuring the deposition of 51-Cr-labeled platelets and by scanning electron microscopy (SEM). Experiments were performed using platelet-rich plasma (PRP) and suspensions of gel-filtered platelets (GFP). Platelets were deposited on C III mainly as surface-bound aggregates. In contrast they were deposited on C IV mainly as spread forms of individual cells. Formation of aggregates on C III was more extensive for PRP than for GFP; in contrast platelet spreading on C IV was more extensive for GFP than for PRP. The effects of an extract of the plant feverfew on platelet-collagen interactions were determined. Feverfew extract inhibited the deposition of 51-Cr-labeled platelets on both C III and C IV in a dose-dependent way. Similar concentrations of extract were needed to inhibit the formation of surface-bound aggregates and to inhibit platelet spreading in both PRP and GFP.

Blood Platelets↗

Hydroxyapatite columns as an in vitro system to study demineralization processes.

Acetate buffers were passed through small hydroxyapatite columns and the column effluents were analysed for calcium and phosphate. Changes in the pH of the column effluents were also measured. As long as the pH of the column effluent was higher than about 5.5, only calcium was eluted from the column. However, when the pH fell below 5.5, the rate of calcium elution decreased and phosphate elution increased until calcium and phosphate elution reached constant values. Pretreating the hydroxyapatite with sodium fluoride or 1-hydroxyethylidene-1,1-bisphosphonate accelerated the drop of the pH and reduced the initial Ca/P ratio in the column effluent. We suggest that these results are due to the formation of a pH gradient along the progressing buffer fron with calcium and phosphate liberated from the hydroxyapatite reprecipitating to form calcium-poor minerals.

Calcium↗

Effects of diamide and iodoacetamide on the expression of the glycoprotein IIb/IIIa complex on blood platelets.

We have examined the effects of two agents that alter platelet thiol-disulphide status on platelet aggregation and on the ability of platelets to bind a monoclonal antibody (M148) that is directed toward an epitope on the glycoprotein IIb/IIIa complex. The immediate effect of both diamide and iodoacetamide is to enhance aggregation but after further incubation diamide, but not iodoacetamide, inhibits platelet aggregation. Incubation of platelets with diamide, but not iodoacetamide, is accompanied by a marked increase in the amount of M148 that binds to platelets. This is presumably a reflection of an altered distribution of glycoproteins on the platelet surface. It is known that diamide, but not iodoacetamide, leads to polymerisation of cytoskeletal proteins in platelets. Thus evidence is provided that agents that interact with the cytoskeleton inhibit platelet behaviour via an effect on surface glycoproteins.

Antibodies, Monoclonal↗

Effect of GSH depletion by 1-chloro-2,4-dinitrobenzene on human platelet aggregation, arachidonic acid oxidative metabolism and cytoskeletal proteins.

Platelet reduced glutathione (GSH) is completely depleted by 1-chloro-2,4-dinitrobenzene (CDNB), which is a substrate for GSH-S-transferase. GSH-depleted platelets: a) aggregate normally at high inducer concentration; b) respond with increased (after arachidonic acid) or depressed (after collagen) aggregability at low inducer concentration; c) show almost no arachidonic acid-induced stimulation of the hexose monophosphate shunt; d) are sensitized to oxidant agents such as diamide, which elicits a faster cytoskeletal protein oxidative polymerization and reversible aggregation. Our results suggest that GSH acts as a reducing cofactor and/or free radical scavenger in the PG-hydroperoxidase step of the cyclooxygenase pathway; moreover, GSH protects membrane and cytoskeletal protein -SH groups from oxidation.

Arachidonic Acid↗

Influence of diamide on aggregation, cytoskeletal proteins, and arachidonic acid metabolism in human platelets.

Simultaneous addition of diamide (azodicarboxylic acid-bis-dimethylamide, DIA), a SH-oxidizing agent, and collagen causes a deaggregation of otherwise irreversibly aggregating platelets. Thromboxane B2 (TXB2) and 12-HE-TE formation is inhibited depending on the concentration ratio between collagen and DIA. Thus, at 0.25 mM DIA and 20 micrograms/ml collagen neither TXB2 nor 12-HETE were measurable, but a full scale reversible aggregation is induced. Deaggregation is further attained by adding DIA to collagen-induced aggregates at a time, when maximum amplitude has been achieved. Investigation of arachidonic acid (AA) metabolites under these conditions revealed no influence of DIA on AA metabolism. Therefore, AA metabolization seems to play a minor role in collagen-induced aggregation and DIA-induced deaggregation. Polymerization of certain cytoskeletal proteins of the platelets, after addition of DIA, parallels DIA-induced deaggregation. DIA inhibits endogenous AA release, probably by interaction with platelet plasma membrane. DIA seems to inhibit the release of the alpha-granula protein thrombospondin.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

[Possible regulatory importance of cellular sulfhydryl groups and reduction metabolic pathways for the activation of human blood platelets].

The activation of the blood platelets is the prerequisite for their participation in physiological and pathological intravasal processes. An aimed influence on the distinct functions of the blood platelets presumes an exact knowledge about course and regulation of the activation of the platelets. Investigations on glucose-6-phosphate-dehydrogenase-deficient platelets and on the effect of glutathione-oxidizing substances on normal platelets showed references to a regulatory significance of the cellular thiol/disulphide state in the process of activation. In this case particularly the arachidonic acid balance and the SH/SS-state of platelet proteins seem to be in close connection with reductive ways of metabolism.

Arachidonic Acids↗

Effect of diamide (azodicarboxylic acid-bis-dimethylamide) on arachidonic acid release from human blood platelet phospholipids.

It was found that the thiol-oxidizing agent diamide inhibits the formation of arachidonic acid metabolites in thrombin-stimulated platelets. An inhibition of arachidonic acid release from membrane phospholipids in diamide-treated platelets is concluded since diamide does not diminish the formation of stable metabolites from exogenous arachidonic acid. The role of the cellular thiol-disulfide status for the activities of phospholipases involved in arachidonic acid release is discussed.

Arachidonic Acid↗

Dependence of arachidonic acid (AA) metabolization in human blood platelets on reduced coenzymes.

In human platelets the metabolization of AA is linked to a consumption of the reduced coenzymes NADPH and GSH which can be attributed to about 70% to the cyclooxygenase (CO) and to about 30% to the lipoxygenase (LO) pathway. In GSH depleted platelets the conversion of AA in the LO pathway to 12-HETE is strongly impaired, whereas the formation of the stable CO products from exogenous AA is not decreased, but accelerated. When platelets are deprived from GSH by oxidation to GSSG, the release of endogenous AA from phospholipids in activated platelets is inhibited.

Arachidonic Acid↗