The effect of circulating adenosine on cerebral haemodynamics and headache generation S Birk et a... more The effect of circulating adenosine on cerebral haemodynamics and headache generation S Birk et al. The effect of circulating adenosine on cerebral haemodynamics and headache generation in healthy subjects
Tienda online donde Comprar Innate Inflammation And Stoke al precio 113,40 € de W. Eisert | G. De... more Tienda online donde Comprar Innate Inflammation And Stoke al precio 113,40 € de W. Eisert | G. Del Zoppo | Phillip Gorelick, tienda de Libros de Medicina, Libros de Neurologia - Neurologia general
Dipyridamole (DP) is an antiplatelet agent that shows decreased oral bioavailability with increas... more Dipyridamole (DP) is an antiplatelet agent that shows decreased oral bioavailability with increased gastric pH that occurs with commonly prescribed antacids. An extended-release (ER) formulation of DP that employs tartaric acid to improve bioavailability of DP in the presence of elevated gastric pH was developed as a combination antiplatelet product with immediate-release aspirin. This crossover-designed study examined the relative bioavailability of DP from the composite product compared to conventional DP tablets during reduced gastric acidity. Gastric pH was increased (pH > 4.0) in 20 healthy subjects with lansoprazole (30 mg/d for 5 days). Dipyridamole systemic exposure over 12 hours was compared after oral administration of a single composite ER capsule (200 mg DP + 25 mg aspirin) versus two 100-mg conventional DP tablets given 6 hours apart combined with 81 mg aspirin. DP relative bioavailability was reduced 53% with conventional tablets compared to the composite buffered ER capsule in reduced gastric acid conditions. Peak DP plasma concentrations were 57% lower with immediate-release tablets compared to the composite formulation with high stomach pH. Substituting generic DP plus low-dose aspirin may be less effective than the buffered DP composite product in patients with concomitant antacid therapies.
XIth International Congress on Thrombosis and Haemostasis
Vascular endothelial cells possess specific receptors for thrombin, and thrombin can interact wit... more Vascular endothelial cells possess specific receptors for thrombin, and thrombin can interact with these receptors to activate the endothelial cells. However, the signal transduction mechanisms which mediate the cellular responses are not yet characterised. The aim of this study therefore, was to determine whether thrombin influenced the inositol phosphate transduction pathway in cultured human endothelial cells. Endothelial cells were isolated from both large and small vessels; these were human umbilical vein and the microvasculature of human omentum respectively. The endothelial cells stained positively with antibodies against Factor VIII antigen and another endothelial cell specific antigen (BMA 120). Pure human thrombin (0.1 - 10 units/ml) induced a dose-dependent formation of inositol phosphate, inositol biphosphate and inositol trisphosphate (IP3) in endothelial cells from large vessels prelabelled with tritiated inositol. The formation of IP3 was significantly increased after...
Pulmonary microembolism is a known complication of massive blood transfusion. The development of ... more Pulmonary microembolism is a known complication of massive blood transfusion. The development of amorphous microparticles in stored blood depends on numerous factors such as time of storage, the kind of stabilisator, and electrical potential as well as morphology of artificial surfaces of blood containers.We have investigated the surfaces of glass and of different plastics used in Western Europe when taking and preserving blood with a scanning microscope. Clear differences have been observed among the different surfaces of plastic tubes and bags with respect to morphology. With increasing roughness there is increasing incidence of irritated thrombocytes adhearing to the surfaces, augmented adhesivness of thrombocytes, and activation of the blood coagulation system. An increase of both amount and size of microparticles as measured by a laser absorption technique, has also been observed.Our results show that the chosen plastics, as well as the way they are produced, effects the genera...
XIth International Congress on Thrombosis and Haemostasis
In view of the therapeutic applications of rt-PA it is of interest to investigate whether there i... more In view of the therapeutic applications of rt-PA it is of interest to investigate whether there is any difference in the lysability between fresh and aged thrombi. The efficiency of fibrinolysis by rt-PA was studied in 3 different ways: In vivo, by measuring the thrombus weight of fresh (1 h) or aged (24 h) thrombi in the carotid artery of rabbits which had been treated with rt-PA (0.4 mg/kg) or saline for 1 h. Ex vivo, by measuring I125-release of in vivo fresh (1 h) and aged (24 h) thrombi (labelled with I125-fibrinogen) suspended in vitro in plasma containing rt-PA (1 μg/ml) ; the thrombi were formed in the jugular vein and the carotid artery of each rabbit. In vitro, by measuring I125-release of fresh (1 h) and aged (6 or 24 h) human native whole blood clots, PPP-clots, PRP-clots and squeezed PPP-clots which were formed and lysed in vitro with rt-PA (1 μg/ml) . In vivo as well as ex vivo rt-PA lysed fresh (1 h) thrombi much better than aged (24 h) thrombi. This difference was mo...
XIth International Congress on Thrombosis and Haemostasis
A new model suitable for the quantitation of Li vivo thrombolytic efficacy was developed which ha... more A new model suitable for the quantitation of Li vivo thrombolytic efficacy was developed which has significant advantages over currently available models. This model allows animals to be used repeatedly and produces data that are less variable.This is a species-independent model utilizing an arterio-venous shunt (AVS). This model was used in rabbits (3 kg) and beagle dogs (13 kg). Each animal was used repeatedly during a 7 day experimental period without evidence of antibody formation. Clot lysis data are less variable than the rabbit jugular vein clot lysis model (RJV). The average coefficient of variation at all doses ([SD/Mean]×l00) with the AVS model was 13±9 and 21±6 for dogs and rabbits, respectively, compared to 25±11 for the RJV model. The rate of data accunulation with the AVS is 3-fold greater than the RJV.In the dog, catheters (25 cm long, 1.6 mm ID) were placed in the jugular vein and the carotid artery, tunneled under the skin to the back of the neck, exteriorized and p...
XIth International Congress on Thrombosis and Haemostasis
Existing models of arterial thrombosis either require extensive surgical intervention or are limi... more Existing models of arterial thrombosis either require extensive surgical intervention or are limited by the short period of observation. Therefore we developed a new model in rabbits to monitor cyclic flow reductions (CFR) due to thrombus formation in a partially denuded and stenosed aorta.An electromagnetic flowprobe was positioned proximally to a stenosis of the abdominal aorta in anesthetized New Zealand rabbits after limited denudation of the vessel using a hemostat. The aortic blood flow was spontaneously reduced due to formation of thrombi. It returned to the basal level after gently shaking the occluder. The…
XIth International Congress on Thrombosis and Haemostasis
Intact endothelial cells are known to form a non-thrombogenic surface and to actively restrict th... more Intact endothelial cells are known to form a non-thrombogenic surface and to actively restrict the extent of thrombus formation on denuded vessel walls via such mechanisms as the binding of thrombin and activation of protein C, or the synthesis and release of prostacyclin. In an in vitro system, we have investigated how platelet inhibitors modulate the antithrombotic effects of human endothelial cells. Human endothelial cells isolated from umbilical veins were plated on one half of a subendothelial matrix (SEM) harvested from bovine cornea endothelial cells. The endothelial cells were preincubated with a drug and then exposed to anticoagulated whole blood from human donors in the presence or absence of the same drug and agitated for 15 min. The number and size of platelets interacting with the SEM were quantified by morphometric analysis.In our in vitro system, platelet aggregates on SEM that was partially covered with human endothelial cells were significantly smaller than on uncov...
ABSTRACT A series of omega-disubstituted alkenoic acid derivatives were designed and synthesized ... more ABSTRACT A series of omega-disubstituted alkenoic acid derivatives were designed and synthesized as antithrombotic inhibitors of thromboxane A2 synthetase and thromboxane A2 receptor antagonists. Hexenoic acid derivatives with a 3-pyridyl group and a 4-(2-benzenesulfonamidoethyl)phenyl substituent were found to be optimal with regard to the dual mode of action. The most potent compound, (E)-6-(4-(2-(((4-chlorophenyl)sulfonyl)amino)ethyl)phenyl)-6-(3-pyridyl) hex-5-enoic acid (36), inhibits thromboxane A2 synthetase in gel-filtered human platelets with an IC50 value of 4.5 +/- 0.5 nM (n = 4), whereas an inhibitory effect on cyclooxygenase is seen only at a much higher concentration (IC50: 240 microM). Radioligand-binding studies with [3H]SQ 29,548 in washed human platelets revealed that 36 blocks the prostaglandin H2/thromboxane A2 receptor with an IC50 of 19 +/- 5 nM (n = 5) and is therefore 85-fold more potent than another combined thromboxane A2 synthetase inhibitor/receptor antagonist, Ridogrel (4). Compound 36 inhibits the collagen-induced platelet aggregation in human platelet-rich plasma and whole blood with an EC50 of 1 microM (Ridogrel: 16 microM) and 100 nM, respectively, and was selected for further development.
We applied multiparameter flow cytometry for the first time to the classification of cells and pa... more We applied multiparameter flow cytometry for the first time to the classification of cells and particles of urine sediments after kidney transplantation. After fluorescent staining with acridine orange, cells and particles were checked for their size and their peak intensity of green and red fluorescences, known to be related to the amounts of intracellular DNA and intracellular RNA, respectively. Urine sediments were tested daily during a period of up to three weeks. Occurrence and disappearance of certain classes of cells and particles were found to be similar among different patients during normal healing. The results from patients without rejection of the graft are suggested as baseline data, differences from which should be detectable with high sensitivity due to the large number of cells being examined.
The effect of circulating adenosine on cerebral haemodynamics and headache generation S Birk et a... more The effect of circulating adenosine on cerebral haemodynamics and headache generation S Birk et al. The effect of circulating adenosine on cerebral haemodynamics and headache generation in healthy subjects
Tienda online donde Comprar Innate Inflammation And Stoke al precio 113,40 € de W. Eisert | G. De... more Tienda online donde Comprar Innate Inflammation And Stoke al precio 113,40 € de W. Eisert | G. Del Zoppo | Phillip Gorelick, tienda de Libros de Medicina, Libros de Neurologia - Neurologia general
Dipyridamole (DP) is an antiplatelet agent that shows decreased oral bioavailability with increas... more Dipyridamole (DP) is an antiplatelet agent that shows decreased oral bioavailability with increased gastric pH that occurs with commonly prescribed antacids. An extended-release (ER) formulation of DP that employs tartaric acid to improve bioavailability of DP in the presence of elevated gastric pH was developed as a combination antiplatelet product with immediate-release aspirin. This crossover-designed study examined the relative bioavailability of DP from the composite product compared to conventional DP tablets during reduced gastric acidity. Gastric pH was increased (pH > 4.0) in 20 healthy subjects with lansoprazole (30 mg/d for 5 days). Dipyridamole systemic exposure over 12 hours was compared after oral administration of a single composite ER capsule (200 mg DP + 25 mg aspirin) versus two 100-mg conventional DP tablets given 6 hours apart combined with 81 mg aspirin. DP relative bioavailability was reduced 53% with conventional tablets compared to the composite buffered ER capsule in reduced gastric acid conditions. Peak DP plasma concentrations were 57% lower with immediate-release tablets compared to the composite formulation with high stomach pH. Substituting generic DP plus low-dose aspirin may be less effective than the buffered DP composite product in patients with concomitant antacid therapies.
XIth International Congress on Thrombosis and Haemostasis
Vascular endothelial cells possess specific receptors for thrombin, and thrombin can interact wit... more Vascular endothelial cells possess specific receptors for thrombin, and thrombin can interact with these receptors to activate the endothelial cells. However, the signal transduction mechanisms which mediate the cellular responses are not yet characterised. The aim of this study therefore, was to determine whether thrombin influenced the inositol phosphate transduction pathway in cultured human endothelial cells. Endothelial cells were isolated from both large and small vessels; these were human umbilical vein and the microvasculature of human omentum respectively. The endothelial cells stained positively with antibodies against Factor VIII antigen and another endothelial cell specific antigen (BMA 120). Pure human thrombin (0.1 - 10 units/ml) induced a dose-dependent formation of inositol phosphate, inositol biphosphate and inositol trisphosphate (IP3) in endothelial cells from large vessels prelabelled with tritiated inositol. The formation of IP3 was significantly increased after...
Pulmonary microembolism is a known complication of massive blood transfusion. The development of ... more Pulmonary microembolism is a known complication of massive blood transfusion. The development of amorphous microparticles in stored blood depends on numerous factors such as time of storage, the kind of stabilisator, and electrical potential as well as morphology of artificial surfaces of blood containers.We have investigated the surfaces of glass and of different plastics used in Western Europe when taking and preserving blood with a scanning microscope. Clear differences have been observed among the different surfaces of plastic tubes and bags with respect to morphology. With increasing roughness there is increasing incidence of irritated thrombocytes adhearing to the surfaces, augmented adhesivness of thrombocytes, and activation of the blood coagulation system. An increase of both amount and size of microparticles as measured by a laser absorption technique, has also been observed.Our results show that the chosen plastics, as well as the way they are produced, effects the genera...
XIth International Congress on Thrombosis and Haemostasis
In view of the therapeutic applications of rt-PA it is of interest to investigate whether there i... more In view of the therapeutic applications of rt-PA it is of interest to investigate whether there is any difference in the lysability between fresh and aged thrombi. The efficiency of fibrinolysis by rt-PA was studied in 3 different ways: In vivo, by measuring the thrombus weight of fresh (1 h) or aged (24 h) thrombi in the carotid artery of rabbits which had been treated with rt-PA (0.4 mg/kg) or saline for 1 h. Ex vivo, by measuring I125-release of in vivo fresh (1 h) and aged (24 h) thrombi (labelled with I125-fibrinogen) suspended in vitro in plasma containing rt-PA (1 μg/ml) ; the thrombi were formed in the jugular vein and the carotid artery of each rabbit. In vitro, by measuring I125-release of fresh (1 h) and aged (6 or 24 h) human native whole blood clots, PPP-clots, PRP-clots and squeezed PPP-clots which were formed and lysed in vitro with rt-PA (1 μg/ml) . In vivo as well as ex vivo rt-PA lysed fresh (1 h) thrombi much better than aged (24 h) thrombi. This difference was mo...
XIth International Congress on Thrombosis and Haemostasis
A new model suitable for the quantitation of Li vivo thrombolytic efficacy was developed which ha... more A new model suitable for the quantitation of Li vivo thrombolytic efficacy was developed which has significant advantages over currently available models. This model allows animals to be used repeatedly and produces data that are less variable.This is a species-independent model utilizing an arterio-venous shunt (AVS). This model was used in rabbits (3 kg) and beagle dogs (13 kg). Each animal was used repeatedly during a 7 day experimental period without evidence of antibody formation. Clot lysis data are less variable than the rabbit jugular vein clot lysis model (RJV). The average coefficient of variation at all doses ([SD/Mean]×l00) with the AVS model was 13±9 and 21±6 for dogs and rabbits, respectively, compared to 25±11 for the RJV model. The rate of data accunulation with the AVS is 3-fold greater than the RJV.In the dog, catheters (25 cm long, 1.6 mm ID) were placed in the jugular vein and the carotid artery, tunneled under the skin to the back of the neck, exteriorized and p...
XIth International Congress on Thrombosis and Haemostasis
Existing models of arterial thrombosis either require extensive surgical intervention or are limi... more Existing models of arterial thrombosis either require extensive surgical intervention or are limited by the short period of observation. Therefore we developed a new model in rabbits to monitor cyclic flow reductions (CFR) due to thrombus formation in a partially denuded and stenosed aorta.An electromagnetic flowprobe was positioned proximally to a stenosis of the abdominal aorta in anesthetized New Zealand rabbits after limited denudation of the vessel using a hemostat. The aortic blood flow was spontaneously reduced due to formation of thrombi. It returned to the basal level after gently shaking the occluder. The…
XIth International Congress on Thrombosis and Haemostasis
Intact endothelial cells are known to form a non-thrombogenic surface and to actively restrict th... more Intact endothelial cells are known to form a non-thrombogenic surface and to actively restrict the extent of thrombus formation on denuded vessel walls via such mechanisms as the binding of thrombin and activation of protein C, or the synthesis and release of prostacyclin. In an in vitro system, we have investigated how platelet inhibitors modulate the antithrombotic effects of human endothelial cells. Human endothelial cells isolated from umbilical veins were plated on one half of a subendothelial matrix (SEM) harvested from bovine cornea endothelial cells. The endothelial cells were preincubated with a drug and then exposed to anticoagulated whole blood from human donors in the presence or absence of the same drug and agitated for 15 min. The number and size of platelets interacting with the SEM were quantified by morphometric analysis.In our in vitro system, platelet aggregates on SEM that was partially covered with human endothelial cells were significantly smaller than on uncov...
ABSTRACT A series of omega-disubstituted alkenoic acid derivatives were designed and synthesized ... more ABSTRACT A series of omega-disubstituted alkenoic acid derivatives were designed and synthesized as antithrombotic inhibitors of thromboxane A2 synthetase and thromboxane A2 receptor antagonists. Hexenoic acid derivatives with a 3-pyridyl group and a 4-(2-benzenesulfonamidoethyl)phenyl substituent were found to be optimal with regard to the dual mode of action. The most potent compound, (E)-6-(4-(2-(((4-chlorophenyl)sulfonyl)amino)ethyl)phenyl)-6-(3-pyridyl) hex-5-enoic acid (36), inhibits thromboxane A2 synthetase in gel-filtered human platelets with an IC50 value of 4.5 +/- 0.5 nM (n = 4), whereas an inhibitory effect on cyclooxygenase is seen only at a much higher concentration (IC50: 240 microM). Radioligand-binding studies with [3H]SQ 29,548 in washed human platelets revealed that 36 blocks the prostaglandin H2/thromboxane A2 receptor with an IC50 of 19 +/- 5 nM (n = 5) and is therefore 85-fold more potent than another combined thromboxane A2 synthetase inhibitor/receptor antagonist, Ridogrel (4). Compound 36 inhibits the collagen-induced platelet aggregation in human platelet-rich plasma and whole blood with an EC50 of 1 microM (Ridogrel: 16 microM) and 100 nM, respectively, and was selected for further development.
We applied multiparameter flow cytometry for the first time to the classification of cells and pa... more We applied multiparameter flow cytometry for the first time to the classification of cells and particles of urine sediments after kidney transplantation. After fluorescent staining with acridine orange, cells and particles were checked for their size and their peak intensity of green and red fluorescences, known to be related to the amounts of intracellular DNA and intracellular RNA, respectively. Urine sediments were tested daily during a period of up to three weeks. Occurrence and disappearance of certain classes of cells and particles were found to be similar among different patients during normal healing. The results from patients without rejection of the graft are suggested as baseline data, differences from which should be detectable with high sensitivity due to the large number of cells being examined.
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