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G V Born

Publications and source records attributed to G V Born.

At least 73 records · Page 4Linked to original sources
PubMed1984

Platelets in atherogenesis and thrombogenesis.

The old thrombogenic hypothesis of atherosclerosis delivered by the Austrian pathologist Carl von Rokitansky has recently appeared in modern costume as claims that platelets contribute to atherogenesis in three ways: through damaging arterial endothelial cells by releasing various agents, the release of a factor responsible for smooth muscle cell proliferation and the formation of persistent mural thrombi being organized into intimal thickenings. An updated view of the role of platelets in atherosclerosis and thrombogenesis is presented in relation to the ideas of Carl von Rokitansky.

Adenosine Diphosphate↗
PubMed1984

[Not Available].

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Germany↗
PubMed1984

The control of bleeding after cardiopulmonary bypass by the intrapericardial instillation of fresh frozen plasma and platelets with microfibrillar collagen.

A technique of, and the results obtained with, the intraoperative and postoperative intrapericardial instillation of microfibrillar collagen and fresh frozen plasma and platelet mixture are presented. Intraoperatively, the mixture was instilled into the exposed mediastinum in the course of open-heart operations in 31 patients in whom diffuse oozing of blood persisted following the termination of cardiopulmonary bypass and the neutralization of circulating heparin. Immediate clot formation and decrease of blood loss were observed in all instances. This method was also found effective in 9 of 20 patients who had continuing blood loss during the hours following open-heart surgery and in whom the mixture was instilled through the mediastinal drainage tubes.

Blood Platelets↗
PubMed1984

Platelets and blood vessels.

The intravascular adhesion and aggregation of platelets initiate hemostasis and arterial thrombosis. In vitro, platelet aggregation is induced by many different agents; which of these is responsible for aggregation in vivo is now under investigation. For this purpose, we have developed novel techniques for the reproducible determination of bleeding times in mesenteric arterioles of rats and rabbits. Local infusions of enzyme systems which remove adenosine diphosphate (ADP) greatly increase the bleeding time at arterial injuries distal to the site of infusion. These observations establish the involvement of ADP in the activation of platelets for primary hemostasis. Direct measurement of free adenosine triphosphate (ATP), as an indicator of ADP, at such injury sites indicates that enough ADP for activating platelets is released very rapidly from damaged vessel walls and much later from the platelets themselves. This bleeding-time technique has also shown that hemostatic platelet aggregation is delayed less by the inhibition of the production of thromboxane A2 than by that of ADP. These observations provide an explanation for the ineffectiveness of any simple platelet-inhibiting drug (including aspirin) by itself, whenever arterial (e.g., coronary or cerebral) thrombosis is initiated by hemorrhages into atheromatous plaques. On the other hand, aspirin is significantly effective when myocardial infarction follows unstable angina and when strokes follow transient episodes of cerebral ischemia. This partial effectiveness can be explained by an action of aspirin on platelets, assuming that, in such cases, their thromboembolic aggregation is initiated by hemodynamic effects of atheromatous lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1984

Delay in primary haemostasis produced by a fish diet without change in local thromboxane A2.

Twelve apparently healthy male volunteers were maintained for 6 weeks on a fish diet, the haemostatic effects of which were determined as standardized skin bleeding times; thromboxane A2 formation in vivo in the bleeding time blood and in vitro in clotting venous blood; platelet aggregability; and platelet phospholipids. Within 1 week the fish diet changed the fatty acid composition of platelet membrane phospholipids, with increases in omega-3 and decreases in omega-6 fatty acids; described platelet aggregability by ADP and collagen; but the bleeding time was unchanged. Not until 6 weeks on the diet did the bleeding time increase (by 37%: P less than 0.01) and it was still increased 3 weeks after the end of the diet, when the fatty acid composition of the platelets had returned to normal. The effect of the diet on decreased aggregability of platelets also failed to follow the changes in their fatty acid composition and in the bleeding time. Aggregation by ADP and by the highest dose of collagen was decreased throughout the diet and for several weeks thereafter, i.e. even when the fatty acid composition had reverted to the pre-dietary pattern and long after the normalization of the bleeding time. The diet caused no change in the in vivo appearance of thromboxane A2 in the bleeding time blood, contrasting with its effect in decreasing the in vitro formation of thromboxane A2 in clotting venous blood. These observations suggest that such fish diets do not delay haemostasis by diminishing the formation of thromboxane A2 locally nor directly by decreasing the aggregability of platelets or directly by the induced changes in their omega-3 fatty acids.

Adult↗
PubMed1984

Source and concentration of extracellular adenosine triphosphate during haemostasis in rats, rabbits and man.

A new technique was developed for the measurement of extracellular free ATP in very small samples of whole blood using the luciferin-luciferase enzyme system. The method had a very low background corresponding to approximately 10(-16) mol ATP. ATP was measured in blood as it emerged during haemostasis following precise puncture of rat and rabbit arteries and after standardized incisions of human skin by the Simplate device. The initial concentration of free ATP in blood emerging 2-4 s after vascular injury was about 2 X 10(-7) M in rats and rabbits and about 2 X 10(-6) M in humans. The free-ATP concentration increased to 2 X 10(-5) M 3-5 min after injury and these increases could be prevented by heparin (20 u./ml). The source of the initial free ATP was identified as damaged cells in the injured vessel wall. Sufficient ADP, both released as such with ATP and generated by enzymic dephosphorylation of ATP, would be present at the site of injury to initiate haemostatic aggregation of platelets.

Adenosine Triphosphate↗
PubMed1984

The role of the platelets.

In the light of the principal pathological findings in coronary thrombosis this contribution deals with the mechanisms responsible for initiating platelet aggregation in an atherosclerotic artery and with the question of how haemorrhage into a ruptured plaque triggers platelet thrombogenesis.

Adenosine Diphosphate↗
PubMed1983

Influence of charge and molecular size on membrane stabilization.

We have reported that the antihaemolytic effect of low concentrations of chlorpromazine is decreased after enzymic removal of sialopeptides from red cell membranes, suggesting that an interaction between negatively charged sialic acids and positively charged chlorpromazine is involved in its membrane stabilizing effect. We have now investigated the antihaemolytic action of simpler molecules with different charges Removal of membrane sialopeptides did not affect the membrane stabilizing actions of simple aliphatic mono- or diamines nor of similar aliphatic molecules carrying strong positive or negative charges, where those positively charged were more potent than those with negative charges. It appears, therefore, that membrane stabilizing activity is determined primarily by lipophilicity and secondarily by polarity and that it does not depend on interactions with enzymically accessible sialopeptides on the outer surface of biological membranes.

Amines↗
PubMed1983

The biologic background to some therapeutic uses of aspirin.

The therapeutic success of aspirin as an effective analgesic, antipyretic, and anti-inflammatory drug had been universally established for many decades before its mode of action was discovered in 1971. This mode of action is the prevention, or diminution, of prostaglandin biosynthesis through the inhibition of the enzyme, cyclo-oxygenase. Demonstrations of the major contributions of prostaglandins to pain, fever, and other cardinal features of inflammation provided rational explanations for the well-established therapeutic uses of aspirin. It had been shown earlier that aspirin antagonized two mediators of inflammation by an indirect process. While aspirin's mode of action was being discovered, research on platelets in hemostasis and thrombosis was also being done. It was shown that aspirin inhibited an exocytotic reaction (the release reaction) of platelets. This reaction was regarded as essential for their aggregation as thrombi in, most importantly, coronary and cerebral arteries. This observation was the starting point of an enormous effort, still going on to determine through both fundamental and clinical investigations, the therapeutic potential of aspirin as an antithrombotic drug. Costly clinical trials have provided evidence in favor of aspirin preventing thrombotic events affecting the brain; its effectiveness against coronary thrombosis is not yet definitely established. Possible explanations for this situation will be considered on the basis of rapidly advancing biologic knowledge about the mechanism of thrombosis.

Animals↗
PubMed1983

Thromboxane A2 in skin-bleeding-time blood and in clotted venous blood before and after administration of acetylsalicylic acid.

The 'Simplate' technique for measuring skin bleeding time was adapted to quantify thromboxane A2 in the emerging blood as the stable degradation product thromboxane B2 in twelve Swedish and ten English volunteers. During the bleeding time thromboxane B2 concentrations increased, but as the rate of blood loss fell the rate of production of thromboxane A2 was constant. The English subjects had shorter bleeding times and produced more thromboxane A2 than the Swedish subjects. When the Swedish subjects were grouped according to bleeding times those with the shortest had more thromboxane A2 than those with longer bleeding times. Clotting venous blood in vitro produced much more thromboxane A2 than bleeding-time blood and there was no correlation with bleeding time. Determination of the capacity of clotting blood to form thromboxane A2 is therefore irrelevant to in-vivo haemostasis. Acetylsalicylic acid greatly diminished the appearance of thromboxane A2 in the bleeding time and prevented the increase of thromboxane A2 concentration with time.

Adenosine Diphosphate↗
PubMed1983

Effects of modification of the membranes of intact erythrocytes on the anti-haemolytic action of chlorpromazine.

Fresh human erythrocytes were washed and incubated at 37 degrees C in physiological saline buffered with Tris, containing calcium and either neuraminidase or trypsin or both enzymes together. Each enzyme alone, as well as both together, released similar amounts of sialic acids without haemolysis, apparently therefore from the same accessible sites on the surface of the cells. Exposure to neuraminidase or/and trypsin did not affect the osmotic fragility of red cells in hypotonic saline. The anti-haemolytic effect of low concentrations of chlorpromazine or thioridazine was diminished by previous exposure of red cells to neuraminidase and/or trypsin. The diminution in the anti-haemolytic effect of chlorpromazine was proportional to the release of sialic acids. The observations suggest that positively charged drugs such as chlorpromazine interact strongly with the negatively charged sialic acid moieties of glycoproteins on cell surfaces, removal of which increases the drugs' access to and disruption of the lipid bilayer in cell membranes.

Chlorpromazine↗
PubMed1983

Hemorheological influences on platelet thrombogenesis.

This lecture is mainly concerned with questions about how hemodynamic conditions in atherosclerotic arteries affect arriving platelets that aggregate there and about the chemical agents responsible for making the platelets reactive. The effects of hemodynamic conditions and the agents are known mainly from in vitro experiments in which aggregation can be quantitatively correlated with blood flow and biochemical effects by simple and reproducible methods; the relevance to the more complicated situations in hemostasis and thrombosis is uncertain. It is difficult to devise quantitative in vivo methods, mainly because of the rapidity with which platelets adhere and aggregate in diseased or damaged blood vessels. Hypotheses for explaining in vivo platelet aggregation in biochemical terms must take the hemodynamic situation into account.

Adenosine Diphosphate↗
PubMed1983

Quantification of blood from skin bleeding time determinations: effects of fish diet or acetylsalicylic acid.

The Simplate II technique for measuring bleeding time was adapted to quantify the volume of blood as a function of time and for determining how this parameter was affected by either acetylsalicylic acid (ASA) or a dietary supplement of fish. Both increased the bleeding time significantly. Irrespective of the final bleeding time, the rate of blood loss increased for about the first 2 min and then decreased almost linearly until bleeding stopped. This time course was not affected by either ASA or the fish diet. The lack of effect by ASA suggests that the initial increase in bleeding time, presumably due to reversal of vasoconstriction, does not involve prostaglandin derivatives. After ASA the rate of blood loss was significantly greater throughout, probably caused by deceleration of platelet aggregation. During the fish diet, when bleeding time was increased, there was no change in the rate of blood loss until the last 2-3 min during which bleeding continued at a very low rate. The results support the conclusion that the delay in primary haemostasis produced by a fish diet is due to a different mechanism than that produced by ASA.

Adult↗
PubMed1983

Uneven distribution of sialic acids on the luminal surface of aortic endothelium.

Lectins which bind sialic acid (aprotinin, wheat germ) were used to measure sialic acid density on the luminal surface of aortic endothelium of rabbit. The bound fluorescein-labelled lectin was released from the sialic acids by the competing ligand N-acetyl-D-glucosamine and measured fluorimetrically. The specificity of the technique was shown by an 80% decrease of bound fluorescence after neuraminidase treatment of the endothelium. Endothelial sialic acid density was the same in the thoracic and abdominal parts of the aorta but significantly less in the arch. Around the orifices of the branches of the intercostal arteries, less surface fluorescence was observed. Ultrastructural studies have shown much less staining of the surface membranes with peroxidase-conjugated wheat germ lectin at these places than elsewhere. These areas, where less sialic acid density was found, coincide with the sites where the atherosclerotic process is known to develop.

Acetylglucosamine↗
PubMed1982

Effect of removing sialic acids from endothelium on the adherence of circulating platelets in arteries in vivo.

The contribution of the net negative charge excess due to sialic acids on endothelium in preventing adhesion of circulating platelets in vivo was investigated in anaesthetized rabbits. Platelets in the rabbit's circulation were selectively labelled with radioactive 5-hydroxytryptamine in vivo. Segments of carotid arteries temporarily isolated from the circulation were perfused with one or other of two commercial preparations of neuraminidase; the opposite carotid artery was perfused similarly without the enzyme, as control. A neuraminidase preparation from Behringwerke free of proteolytic activity released sialic acid into the perfusate with a peak concentration after 10-15 min which decreased gradually later. A neuraminidase preparation from Sigma that contained demonstrable proteolytic activity released sialic acid similarly during the first hour and thereafter more sialic acid in a second peak. After blood flow through the carotids had been restored the adhesion of labelled platelets in the artery perfused with neuraminidase was compared with that in the artery perfused without the enzyme. The radioactivities were significantly higher in carotids that had been perfused with neuraminidase than in those that had been perfused without the enzyme. Neuraminidase perfusion had no effect on the production of prostacyclin by the carotids. Perfusion with acetylsalicylic acid before neuraminidase increased the adhesion of platelets significantly. It is concluded that diminution in electrostatic repulsion between circulating platelets and vascular endothelium from which the net negative charge excess due to sialic acids has been removed increases the adhesion of circulating platelets, irrespective of the production of prostacyclin by the arterial walls, and that inhibition of prostacyclin production augments this adhesion of platelets.

Animals↗