PubMed Health⌕ Search

Biomedical subjects

M Dryjski

Publications and source records attributed to M Dryjski.

36 records · Page 2Linked to original sources
PubMed1989

Investigations on plasma activity of low molecular weight heparin after intravenous and oral administrations.

This study investigated the absorption of low molecular weight heparin (LMWH) after oral administration in man. Six healthy subjects received 5,000 anti-Xa units of LMWH (Kabi 2165) by both i.v. and oral administration. The oral formulations were prepared in pH 4.0 and pH 7.0 buffered solutions. Multiple blood samples were collected after each dose for measurements of anti-Xa, anti-IIa and APTT plasma heparin activities. Pharmacokinetic parameters based on the anti-Xa activity measurements after the i.v. dose were as follows (mean +/- s.d.): t1/2, 1.82 +/- 0.23 h; V, 4.34 +/- 0.651; and CL, 28.0 +/- 6.2 ml min-1. Half-life values based on the anti-IIa and APTT activities were 1.63 +/- 0.43 and 1.09 +/- 0.51 h, respectively. Considerable prolongations in APTT were observed, with APTT at 30 min averaging 55.7 +/- 4.1 s (1.84 +/- 0.27 times baseline values). After oral administration, no measurable plasma heparin activities were observed with either LMWH preparation. The results of this investigation indicate that LMWH does not have detectable plasma activity after oral administration, and that after i.v. administration it has significant anti-IIa and APTT activities in addition to its anti-Xa activity.

Administration, Oral↗
PubMed1988

Interaction of thrombin and factor Xa with bovine vascular endothelial cells, smooth muscle cells and rat hepatoma cells.

The aims of the present investigation were to characterize the binding and inhibition of thrombin and factor Xa to bovine vascular endothelial cells (EC), bovine smooth muscle cells (SMC), and rat hepatoma cells (RHC), and to evaluate the effects of plasma constituents on their inhibition. The enzymatic activities of bovine thrombin and factor Xa were assayed using chromogenic substrates. After 10 min incubation with the cells, thrombin activity in the solution had decreased by about 20% and was subsequently recovered on the cell surfaces. When the cells with the surface-bound thrombin were incubated with defibrinogenated plasma or antithrombin III (AT-III) for 30 sec only about 10% and 20-40%, respectively, of the initial activity could be recovered. In similar experiments with factor Xa, initial activity in the solution had decreased by 10% after 10 min incubation, and was subsequently recovered from the cell surfaces. After 30 sec incubation with AT-III, no cell surface-bound factor Xa activity was detected, whereas 10% of the bound factor Xa activity was recovered after incubation with defibrinogenated plasma. It is concluded that thrombin and factor Xa are taken up and inhibited by EC, SMC and RHC cell surfaces in similar ratios, suggesting that cell surface-mediated inhibition of clotting factors is not restricted to vascular wall cells. The inactivation of factor Xa was dependent on AT-III, however, the inactivation of thrombin was further promoted by an additional unidentified plasma constituent.

Animals↗
PubMed1988

Role of polyamines in the stimulation of synthesis and secretion of plasminogen activator from bovine aortic endothelial cells.

The effects of the polyamines putrescine (PUT), spermidine (SPD), and spermidine (SPM) on the secretion of plasminogen activator (PA) and plasminogen activator inhibitor (PAI) were evaluated using cultured bovine aortic endothelial cells. All three polyamines enhanced PA secretion in a time- and dose-dependent manner, with a potency rank order of SPM greater than SPD greater than PUT. The PA stimulation required both RNA and protein synthesis, as evidenced by inhibition of polyamine-induced PA secretion by actinomycin D and cycloheximide. The inhibitors of polyamine biosynthesis methylglyoxal bis-(guanylhydrazone) (MGBG) and dl-(difluoromethyl) ornithine (DFMO) alone did not affect basal or polyamine-induced PA secretion, with the exception that MGBG reduced the effect of PUT. Polyamine-treated cells enhanced secretions of both tissue-type and urokinase-type PA. The results of the present study suggest that polyamines may play a role in the regulation of PA synthesis and secretion and that this function can be modified under pathophysiological conditions affecting cellular and tissue levels of polyamines.

Animals↗
PubMed1988

Inhibition of intimal hyperplasia after arterial injury by heparins and heparinoid.

The efficacies of standard heparin (SH), low molecular weight heparin (LMWH), and a mixture of sulfated glycosaminoglycans (Org 10172) were investigated with respect to their inhibitory effects on intimal thickening after endothelial injury in the common carotid artery of the rat. The injury was induced by air infusion into an isolated segment of the artery; the pharmacologic agents were administered by continuous intravenous infusion. After 2 weeks the animals were killed and the arteries examined. The control animals developed a marked intimal thickening. A dose-dependent decreases in the intima to media area (I-M) ratio was seen after SH, with approximately 50% and 90% inhibition of intimal thickening at doses of 5 and 50 USP U/kg/hr, respectively. At these effective doses, the effect of SH was associated with reendothelialization of the injured area. The effects of LMWH and Org 10172 were similar to that of SH at doses of 50 anti-Xa U/kg/hr, but these agents had only about 40% inhibition at doses of 15 anti-Xa U/kg/hr. The activated partial thromboplastin times were slightly prolonged in the animals treated with 50 USP/anti-Xa U/kg/hr of SH, LMWH, and Org 10172, whereas significant anti-Xa levels were observed at doses higher than 15 USP/anti-Xa U/kg/hr. It is concluded that SH, LMWH, and Org 10172 have significant inhibitory effects of intimal thickening after injury even at nonanticoagulant levels, with SH being the most potent.

Animals↗
PubMed1986

Thrombin uptake and inhibition on endothelium and surfaces with a stable heparin coating: a comparative in vitro study.

The endothelial lining and two differently heparin-coated surfaces were compared in vitro regarding thrombin uptake and inhibition. One heparin surface was based on stabilized ionic binding of heparin, the other on covalent binding of partially degraded heparin. Both heparin surfaces have previously been shown to have pronounced thromboresistant properties. The two heparinized polyethylene surfaces and the endothelial surface of segments of the porcine aorta were studied. After exposure to the surfaces, thrombin disappeared from the solution and appeared bound to the surfaces. The disappearance rate of thrombin from the solution was the same on exposure to the endothelium and the covalently bonded heparin surface, but less following exposure to the ionically bonded heparin surface. The thrombin activity appearing on the endothelium was lower than on the heparin surfaces, indicating that the endothelium exerted a slow thrombin inhibiting capacity. On exposure of the thrombin-loaded endothelium to plasma, thrombin was rapidly inhibited. Thrombin bound to the covalently bonded heparin surface was inhibited at a slower rate than on the ionically bonded surface, but still faster than the rate at which free thrombin was inhibited in nonheparinized plasma. It is concluded that the endothelium and stabilized heparin coatings bind thrombin and accelerate its inhibition by plasma.

Animals↗
PubMed1985

Thrombin activity appearing on the vessel wall after trauma.

Thrombin activity was assayed on the aortic surface of rabbits after soft tissue trauma or endothelial injury caused by a balloon catheter. The animals were sacrificed by exsanguination 20 minutes or 3 hours after either type of trauma. Thrombin amidolytic activity on the luminal surface of the aorta was measured by exposing it to a synthetic chromogenic substrate. Thrombin activity appeared on the aortic endothelium 3 hours but not 20 minutes after soft tissue trauma. Heparin prevented the appearance of thrombin activity completely only if given just before the trauma. After endothelial injury, thrombin activity appeared on the vascular surface after 3 hours but not after 20 minutes. Thrombin activity appearing on the endothelium after soft tissue trauma may explain posttraumatic thrombotic events. The thrombin activity could, however, also be directed towards activation of protein C in which case an anticoagulant effect is obtained. Thrombin appearing after endothelial injury may enhance reactivity on the damaged vessel wall.

Animals↗
PubMed1985

Uptake and inactivation of thrombin on rabbit aortic endothelium studied with two different substrates.

The endothelium is an important compartment for uptake and inhibition of thrombin. The amount of enzymatically active bound thrombin can be detected with both small synthetic substrates and with aid of fibrinogen as substrate. The present study was designed to investigate the relation between endothelially bound thrombin with amidolytic activity towards a synthetic substrate (S-2238) and thrombin capable of converting fibrinogen by measuring generation of fibrinopeptide A (FPA). The luminal surfaces of rabbit aortae (2 cm2) were exposed in vitro to thrombin (0.625-5.0 NIH units/ml). Thrombin disappeared from the solution and a certain fraction was recovered on the surface. There was a linear relationship between the amount of thrombin on the surface and the concentration of thrombin in the incubation mixture. Approximately one third of the thrombin measured with S-2238 was also able to cleave fibrinogen. After incubation with defibrinogenated plasma almost total inhibition of fibrinogen splitting activity occurred within 30 sec. The inhibition of the amidolytic activity was less complete. When endothelially bound thrombin was exposed to plasma much less FPA was generated than in a fibrinogen solution. A minor fraction of endothelially bound thrombin was inhibited also upon incubation with Tyrode without recovery of any enzymatic activity in the solution. The results indicate that a fraction of thrombin bound to the endothelium has retained enzymatic activity and that a fraction of the enzymatically active thrombin is capable of converting fibrinogen. Inhibition of thrombin enzymatic activity occurs rapidly upon exposure to plasma. The endothelium itself has a minor inhibitory effect also in the absence of plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Uptake and inactivation of thrombin on aortic endothelium and neo-intima.

The aim of this study was to investigate the uptake and inactivation of thrombin on aortic endothelium and neo-intima developing on vascular grafts in pigs and dogs. Thrombin, measured with a synthetic chromogenic substrate, was found on the grafts, particularly on grafts with an incompletely developed neo-intima. After incubation of grafts and aortic segments with thrombin in vitro, significantly more thrombin was taken up on the grafts as compared to aortic endothelium. In the presence of plasma, surface-bound thrombin was inactivated much faster on aortic endothelium than on neo-intima. If surfaces loaded with thrombin in vitro were incubated with a balanced salt solution the enzyme was inhibited much more slowly. Thrombin activity on the neo-intima may contribute to graft thrombosis.

Animals↗
PubMed1985

Acute nontraumatic extremity ischaemia in Sweden. A one-year survey.

An attempt was made to evaluate the results of treatment for acute nontraumatic extremity ischaemia in Sweden during one year. A questionnaire was sent to all surgical units, and 61% replied. Of the total 586 evaluated cases, 497 were classified as embolism and 89 as acute thrombosis. Patient age strongly influenced results in both groups as regards limb salvage and mortality rates. The site of embolic occlusion also influenced mortality, with greatly heightened rate in aortic occlusion. Delay of operation for more than 12 hours after onset of symptoms was associated with increase in amputation rate and mortality. Adequate heparin therapy significantly improved results after embolectomy, but had no such effect after surgical treatment of thrombosis. The amputation rate was higher after acute thrombosis than after embolism. The authors conclude that patient age should be considered in comparisons between different case series of acute ischaemia, that embolus site and time of surgery are important determinants of mortality and amputation rate, and that heparin significantly improves results of embolectomy.

Adult↗
PubMed1983

Effect of glycosaminoglycans and antithrombin III on uptake and inhibition of thrombin by the vascular wall.

Thrombin binds to and is inactivated by the endothelium. The inactivation is potentiated by plasma. The present investigation was designed to clarify the role of vessel wall glycosaminoglycans (GAG) and plasma antithrombin III (AT III) in the inactivation and binding of thrombin by endothelium. Thrombin was shown to bind to vascular endothelium and artificial surfaces containing GAG:s. The binding could be inhibited on both types of surfaces by pretreating them with protamine. Thrombin bound to endothelium was rapidly inactivated in the presence of plasma but only slowly if the plasma was replaced by AT III, AT III-depleted plasma or a balanced salt solution. It is concluded that thrombin binds to vessel wall GAG:s and is inactivated by the endothelium. Potentiation of the inhibition of the endothelially bound thrombin by plasma is dependent upon presence of AT III but an additional plasma factor is also required.

Animals↗
PubMed1983

Inactivation of thrombin by the aortic endothelium.

The aim of the investigation was to clarify the uptake of thrombin on vascular endothelium and the inhibition of thrombin on the endothelium in the presence or absence of plasma. Segments of porcine aorta were used. Thrombin was labelled with 125I and its enzymatic activity was assayed amidolytically using a specific chromogenic substrate. After exposure to the endothelium both enzymatic activity and radioactivity disappeared from the thrombin solution and were recovered as surface bound activities. The enzyme activity confined to the endothelium rapidly disappeared in the presence of plasma but no activity was recovered in the plasma. The surface confined radioactivity, however, decreased slowly and was quantitatively recovered in the plasma. In the absence of plasma, i.e. in the presence of a balanced Ringer's solution, only slow disappearance of thrombin enzymatic activity occurred although the rate of disappearance was higher than that of release of radioactivity. It is concluded that thrombin, taken up on the endothelium, is almost instantaneously inhibited by an interaction mechanism with plasma and then released in an inactive state. The endothelium itself, however, seems to slowly inhibit bound thrombin and then release it.

Animals↗
PubMed1983

The vascular endothelium as an inhibitor of thrombin.

Uptake and inhibition of thrombin on the endothelium of porcine aorta was studied in vitro. The thrombin was labelled with 125J and its enzyme activity was measured with an amidolytic assay. After exposure to the aorta both the enzyme activity and radioactivity disappeared from the solution and were recovered as surface bound activities. The rate of inhibition of the surface bound thrombin was determined in presence or absence of plasma. In presence of plasma the endothelially confined enzymatic activity was rapidly inhibited, no enzymatic activity was recovered in plasma. The surface bound radioactivity, however, decreased slowly and was recovered in plasma. In absence of plasma only slow inhibition took place. It is concluded that thrombin taken up on the endothelium is rapidly inhibited there by an interaction with plasma and then released in an inactivated state. An alternative conclusion, based on the anticoagulant and antithrombotic actions of the endothelial fibrin lining is briefly discussed.

Animals↗
PubMed1983

The vascular endothelium as an inhibitor of thrombin.

Uptake and inhibition of thrombin on the endothelium of porcine aorta was studied in vitro. The thrombin was labelled with 125J and its enzyme activity was measured with an amidolytic assay. After exposure to the aorta both the enzyme activity and radioactivity disappeared from the solution and were recovered as surface bound activities. The rate of inhibition of the surface bound thrombin was determined in presence or absence of plasma. In presence of plasma the endothelially confined enzymatic activity was rapidly inhibited, no enzymatic activity was recovered in plasma. The surface bound radioactivity, however, decreased slowly and was recovered in plasma. In absence of plasma only slow inhibition took place. It is concluded that thrombin taken up on the endothelium is rapidly inhibited there by an interaction with plasma and then released in an inactivated state. An alternative conclusion, based on the anticoagulant and antithrombotic actions of the endothelial fibrin lining is briefly discussed.

Adsorption↗
PubMed1982

Uptake and inhibition of thrombin by the vascular wall.

Thrombin activity and inhibition were assayed on the aortic surface of dogs and pigs. After sacrifice, the aortae were excised and thrombin activity was measured with an amidolytic assay. A small thrombin activity was found on the endothelium. Heparinization of the animals lowered endothelial thrombin activity. After exposure of the aortic endothelium to a thrombin/albumin solution in vitro, thrombin activity disappeared from the solution and was recovered on the surface. De-endothelialized vessels took up more thrombin than those with intact endothelium. Endothelium confined thrombin was rapidly inactivated when exposed to plasma. A slow inactivation was seen upon exposure to a modified Ringer's solution. Thrombin confined to de-endothelialized aortae, i.e. to medial structures, was always inactivated at a slow rate irrespective as to whether it was exposed to plasma or Ringer's solution. It is concluded that endothelium and subendothelium bind thrombin and subsequently inactivate it. The inactivation proceeds faster on endothelium when exposed to plasma. The possible role of glycosaminoglycans is discussed.

Animals↗
PubMed1982

Septic false aneurysms. Report of three cases.

Three cases of septic false aneurysms are reported. They appeared as palpable pulsating masses shortly after severe septic episodes and were diagnosed by angiography. Two aneurysms were located in the common iliac artery and one in the superficial femoral artery. Operation was performed under antibiotic coverage and included ligation of the artery and excision of the aneurysm. Immediate reconstruction was performed in one case, in the two remaining, such reconstruction was abstained from since intraoperative ankle pressures were judged adequate. In one case reconstruction was performed later to relieve claudication. All patients survived with functioning extremities.

Adult↗
PubMed1982

Acute thrombosis and embolism of the extremities: factors influencing the result of treatment.

Eighty-five cases treated for acute nontraumatic ischemia of the extremities have been reviewed. Eighty per cent were diagnosed as emboli and the remaining 20% were considered to have acute thrombosis. The most common embolism source was the heart and the most common heart disease causing embolism was atrial fibrillation. Seventy patients were treated surgically (80 surgical procedures) and 14 conservatively. All surgical patients received pre-, per- and postoperative anticoagulants. Limb-salvage rate was 76% in patients with emboli and 60% in the thrombosis group. The amputation rate was significantly higher in the thrombosis group. The overall mortality was 12% and was slightly but not significantly higher in the embolism group. It is concluded that acute arterial emboli should be treated rapidly by embolectomy. Acute thromboses carry a higher amputation rate if treated by thrombectomy alone and thus reconstruction should be considered. The relatively low mortality rate in the present material could be due to the routine use of anticoagulants.

Adolescent↗
PubMedDate not supplied

Acute ischemia of the extremities in a metropolitan area during one year.

All acute extremity ischemias during one year (1980) in the greater Stockholm area (population 1.5 million) were evaluated. One hundred and thirty eight cases were found. The incidence figures varied from 0.4/100,000 in the age group 20 to 30 years to 182/100,000 in the ages above 90 years. 81% of the cases were classified as emboli and 19% as acute thrombosis. Over all mortality was 19.5%. In the embolism group mortality was 21%, amputation rate 28% and limb salvage rate 51%. Limb salvage rate was significantly higher in patients receiving heparin therapy (61%) as compared to those who received no heparin (32%). Delay of treatment also caused an increase in amputation rate. Patients with acute thrombosis had a lower mortality (12%) and an amputation rate of 42%. It is concluded that the results of acute extremity ischemia may be less favourable than previously reported when results from institutions not specialised in vascular surgery are also included. Among other possible factors explaining the high amputation rate may be the proportion of older patients.

Acute Disease↗