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Biomedical subjects

P Olsson

Publications and source records attributed to P Olsson.

At least 109 records · Page 6Linked to original sources
PubMed1987

Antithrombin III binding to surface immobilized heparin and its relation to F Xa inhibition.

The mode of F Xa inhibition was investigated on a thromboresistant surface with end-point attached partially depolymerized heparin of an approximate molecular weight of 8000. Affinity chromatography revealed that one fourth of the heparin used in surface coating had high affinity for antithrombin III (AT). The heparin surface adsorbed AT from both human plasma and solutions of purified AT. By increasing the ionic strength in the AT solution the existence of high and low affinity sites could be shown. The uptake of AT was measured and the density of available high and low affinity sites was found to be in the range of 5 and 11 picomoles/cm2, respectively. Thus the estimated density of biologically active high and low affinity heparin respectively would be 40 and 90 ng/cm2. The heparin coating did not take up or exert F Xa inhibition by itself. With AT adsorbed on both high and low affinity heparin the surface had the capacity to inhibit several consecutive aliquots of F Xa exposed to the surface. When mainly high affinity sites were saturated with AT the inhibition capacity was considerably lower. It was demonstrated that the density of AT on both high and low affinity heparin determines the F Xa inhibition capacity whereas the amount of AT on high affinity sites limits the rate of the reaction. This implies that during the inhibition of F Xa there is a continuous surface-diffusion of AT from sites of a lower class to the high affinity sites where the F Xa/AT complex is formed and leaves the surface. The ability of the immobilized heparin to catalyze inhibition of F Xa is likely to be an important component for the thromboresistant properties of a heparin coating with non-compromised AT binding sequences.

Animals↗
PubMed1986

Thrombin inactivation on surfaces with covalently bonded heparin.

About 8000 Daltons porcine mucosa heparin fragments were covalently bonded by end-point attachment to polyethylene. The interaction between the immobilized heparin, added thrombin, and antithrombin III [AT] was investigated. The heparin surface was adsorbed with either albumin, AT dissolved in albumin or Tyrode, or platelet free plasma. Irrespective of the pre-treatment procedure, exposure of the surface to thrombin resulted in the same substantial decrease of thrombin in solution and the same degree of surface-confined thrombin activity. It was concluded that the heparin surface has a large capacity to bind thrombin and that the thrombin inhibitory capacity of high affinity heparin fragments is limited. On exposure of the thrombin-loaded surfaces to defibrinogenated plasma or AT, the surface-confined thrombin was inhibited within 30 seconds. Successive dilutions of plasma or AT decreased the inhibition rate but not the inhibition capacity. It is concluded that inhibition of thrombin adsorbed on the heparin surface occurs as follows: Added AT adheres to high affinity heparin fragments on the surface whereupon adsorbed thrombin migrates in the hydrophilic heparin coating towards the reaction site of AT and becomes inhibited. The inactivated thrombin-AT complex leaves then the surface, thus enabling the process to be repeated.

Antithrombin III↗
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↗
PubMed1986

Endotoxin: routes of transport in experimental peritonitis.

A quantitative endotoxin assay was applied in this study of endotoxin transport from the infected abdomen. In rats with fecal peritonitis, extremely high concentrations were found in thoracic duct lymph (approximately 400 times higher than those found in arterial and portal vein plasma). Taking flow rates into account, the thoracic duct carries 34 ng/hour and the protal vein 49 ng/hour after 2 hours of peritonitis. Endotoxin quantities transported by the portal vein never exceed the proposed endotoxin filtrating capacity of the liver. Furthermore, the onset of systemic endotoxemia parallels the appearance of endotoxin in the thoracic duct. The hypothesis put forward is that the development of systemic endotoxemia is mainly mediated by lymphatic transport. The results also indicate that endotoxin is normally absorbed from the intestine and transported by portal blood.

Animals↗
PubMed1986

Effect of leukotriene D4 on nasal mucosal blood flow, nasal airway resistance and nasal secretion in humans.

The possible role of leukotriene D4 (LTD4) in nasal allergy was investigated in healthy volunteers. Nasal blood flow, nasal airway resistance, nasal discharge and nasal itching and sneezing were examined. LTD4 was found to induce a dose-response related increase in nasal mucosal blood flow as measured by laser-Doppler flowmetry. Histamine exhibited similar effects on blood flow in the same concentration range. Nasal airway resistance as recorded by rhinomanometry, increased in a dose-related manner after topical LTD4. Nasal secretion was obtained by nasal lavage and estimated from a dilution principle. Topical LTD4 did not increase the amount of nasal secretion, whereas a dose-related increase was found after topical histamine. LTD4 did not cause itching, sneezing or other irritative symptoms. In conclusion, LTD4 may play a role in nasal allergy by increasing blood flow and nasal airway resistance. Itching, sneezing and discharge, however, are apparently not caused by LTD4 but can be accounted for by the release of histamine or other mediators.

Administration, Topical↗
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

Effects of different anticoagulants on human platelet size distribution and serotonin (5-HT) induced shape change and uptake kinetics.

The effect of collecting blood with disodium ethylene diamine tetraacetate (EDTA), citrate (NAC) or acid sodium citrate-dextrose (ACD) as anticoagulants on platelet count and size distribution was investigated. No difference between the three preparations regarding platelet count was found in whole blood. Preparation of platelet-rich plasma (PRP) significantly reduced the platelet count in NAC-PRP (p less than 0.01) to a value of 288 X 10(9)/l compared to those of 365 X 10(9)/l and 368 X 10(9)/l in EDTA and ACD blood respectively. A significant shift in the platelet size in EDTA-PRP towards larger cell volumes was observed. There were no differences in the size distribution pattern between NAC-PRP and ACD-PRP in spite of the differences in platelet count. Platelet 5-HT uptake kinetics in EDTA-PRP showed a 50 per cent reduction in both Km and Vmax compared to that in ACD-PRP. The study shows that the receptor mediating 5-HT induced shape change has a direct opposite pH dependence than that of the 5-HT carrier. Interference of receptor-mediated responses in 5-HT uptake studies in human platelets is clearly minimized at a lowered pH. The finding is probably of importance in disorders associated with platelet hyperaggregability.

Adenosine Diphosphate↗
PubMed1985

The effects of citalopram (Lu 10-171) on the serotonin (5-HT) uptake kinetics in platelets from endogenously depressed patients.

The uptake kinetics of serotonin (5-HT) in platelets from eight patients with endogenous depression was determined in platelet rich plasma (PRP). From the uptake data the Scatchard correlation coefficient (r[S] ), Sips' index of heterogeneity (alpha), Km and Vmax (Lineweaver-Burk) were calculated. The measurements were performed before and after two weeks treatment with Citalopram, 1-(3-dimethylaminopropyl)-1-(p-fluorophenyl)-5-phtalan carbonitrile (Lu 10-171), a selective 5-HT uptake inhibitor. After two weeks treatment with Citalopram (5, 25 or 50 mg/day) a lowered platelet count in whole blood and PRP was observed and none of the patients had a measurable 5-HT uptake for which kinetic parameters (Km and Vmax, Lineweaver-Burk) could be calculated. However, all the patients but one improved significantly in Global score.

Adult↗
PubMed1985

Haemodialysis in dogs with a heparin coated hollow fibre dialyser.

Haemodialysis was performed in non-uraemic dogs with equipment coated with a stable heparin. During a three hour dialysis a constant blood flow of 205 ml/min was easily maintained. There was no increase in whole blood coagulation time and no heparin release from the surface. The platelet count was initially reduced by 15 per cent, but remained constant at this value throughout the dialysis. No increase in FPA concentration was detected. Heparin coating on inherently thrombogenic materials enables haemodialysis in the absence of systemic anticoagulation and without measurable activation of the haemostatic mechanism.

Animals↗
PubMed1985

Endotoxin-transport routes and kinetics in intestinal ischemia.

A rat model representing segmental intestinal ischemia was used to study the absorption and transport of endotoxin from the ischemic gut. Serial quantitative analyses were made on peritoneal fluid, thoracic duct lymph and arterial and portal vein blood. Significantly increased endotoxin concentrations were found in thoracic duct lymph before transmural leakage took place. After leaking through the devitalized intestinal wall, endotoxin was transported by both lymphatic and portal routes. Kinetic analysis revealed that systemic endotoxemia paralleled the appearance of endotoxins in thoracic duct lymph, preceding a significant increase in the portal vein. The amount transported by the portal vein never exceeded the proposed endotoxin-filtrating capacity of the liver. In intestinal ischemia, consequently, systemic endotoxemia appears to be mediated mainly by lymphatic transport.

Animals↗