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Biomedical subjects

B Osterud

Publications and source records attributed to B Osterud.

At least 73 records · Page 4Linked to original sources
PubMed1990

The function of granulocytes and alveolar macrophages following a single dose of endotoxin in rabbits. Effects of methylprednisolone.

It is a generally held opinion that steroids attenuate the activation of phagocytes. However, this statement has its limitations; in rabbit endotoxemia, for instance, steroids enhance the procoagulant activity of monocytes. The present study aimed to investigate the release of toxic oxygen metabolites (TOM) from granulocytes and alveolar macrophages 24 h after endotoxin injection in rabbits, and the effect of concomitant injection of methylprednisolone (MP). Release of TOM was assessed by peak chemiluminescence (CLP). Expression of thromboplastin activity by alveolar macrophages was determined as well, employing a recognized method for assessment of activity. In terms of mean +/- s.e.mean, endotoxin increased granulocyte count from a baseline value of 1.8 +/- 0.2 X 10(6) cells/ml to 3.7 +/- 1 X 10(6) cells/ml, which increased further to 9.8 +/- 2.5 X 10(6) cells/ml following administration of MP. Whereas endotoxin given alone caused no significant change in granulocyte CLP, additional administration of MP increased CLP from 1723 +/- 389 to 16610 +/- 8428 counts. On the other hand, MP attenuated an endotoxin-induced increase in both CLP and thromboplastin activity of alveolar macrophages. Thus, MP appears to have a proinflammatory effect on circulating granulocytes in rabbit endotoxemia, simultaneously depressing the function of stationary macrophages. This may suggest an injurious effect of MP in rabbit endotoxemia.

Animals↗
PubMed1990

The production of tumour necrosis factor, tissue thromboplastin, lactoferrin and cathepsin C during lipopolysaccharide stimulation in whole blood.

The release of tumour necrosis factor (TNF), lactoferrin (LF) and cathepsin C (CC) into plasma and production of thromboplastin (TPL) in monocytes were studied in lipopolysaccharide (LPS) stimulated heparinized whole blood from 10 healthy donors. The influence of dextran 70, haemaccel and methylprednisolone on levels of these parameters were examined. TNF concentration in plasma 5 min after the addition of LPS (0 h) was 250 pg/ml (median), 520 pg/ml after 1 h and 1300 pg/ml after 3 h. The addition of dextran 70 to the blood in addition to LPS at the same intervals gave significantly higher values of 740 pg/ml and 1800 pg/ml after 1 h and 3 h respectively. Unstimulated cells had no TPL but after 1 h with LPS, the TPL activity in incubated cells was 2.3 mU/10(6) monocytes and after 3 h, 2.7 mU/10(6) monocytes. LPS induced the secretion of LF from granulocytes (PMN) and the levels 5 min after the addition of LPS (0 h) were 2.1 mg/l (control 0.2 mg/l) and after 1 h, 5.3 mg/l (control 1.3 mg/l) in plasma after LPS stimulation. Haemaccel enhanced the LPS-induced generation of TPL in monocytes and production of CC. The LPS-induced secretion of LF was, to a small extent, influenced by the three reagents tested. Methylprednisolone (1 mmol/l) reduced the production and appearance of TNF in plasma and the generation of TPL activity in monocytes. This model for stimulating heparinized whole blood is suitable for examination of the production and appearance of cellular factors and the influence of drugs on this production.

Adult↗
PubMed1990

Factor VII and haemostasis.

The role of factor VII in the haemostatic mechanism as well as thrombosis has recently gained new interest. Today's concept that factor VII may be a key regulator in the initiation of blood coagulation is based on studies that provide new evidence for a mandatory activation of factor VII to factor VIIa in blood. Exposure of thromboplastin to the circulation may not trigger activation of blood coagulation before the one chain factor VII is converted to the active two chain form of factor VIIa. A hypothetical model is proposed for the initiation and subsequent activation steps of the blood coagulation process. In this model, it is suggested that circulating activators of factor VII activate inactive complexes of thromboplastin-factor VII. Subsequently, newly generated factor Xa will accelerate this reaction and thereafter be the most potent activator of factor VII. This model would also fit with the clinical observation that moderate factor VII deficiency may be associated with thrombotic episodes discussed in this communication. This article also discusses the role of recombinant factor VIIa in the treatment of factor VIII deficiency patients with acquired factor VIII inhibitors, factor VII and ischemic heart disease and the factor VII-phospholipid complex, and the regulation of the thromboplastin-factor VIIa complex by factor Xa and extrinsic pathway inhibitor (EPI).

Blood Coagulation↗
PubMed1990

Lack of ability to synthesize tissue factor by endothelial cells in intact human saphenous veins.

It is well established that cultured endothelial cells are induced to generate tissue factor activity when incubated with either endotoxin or thrombin. In this study a perfusion system was used on 3-4 cm long human saphenous veins. The veins were perfused with thrombin (2.5 U/ml), endotoxin (30 ng/ml) or just medium for 3 h at 37 degrees C. After the perfusion, the veins were treated with collagenase, and EC were collected and subjected to tissue factor activity measurements. Some perfused veins were examined for tissue factor activity on the vessel wall by allowing factor VII and factor X to interact with the lumen of the intact vessels, followed by quantitation of generated factor Xa in a chromogenic assay. No formation of tissue factor activity could be found after perfusion in either collagenase-dissolved endothelial cells or in the coupled chromogenic assay for tissue factor activity performed in the lumen of the vessel. Our data strongly suggest that endothelial cells in intact endothelium may behave quite differently from isolated endothelial cells stimulated in cell cultures.

Adult↗
PubMed1989

The effect of lipopolysaccharides (LPS) on generation of thromboxane A2 and thromboplastin activity in whole blood of males, females and females on oral contraceptives.

Heparinized blood sample taken from 81 healthy persons, 40 men and 41 women of whom 17 were on combined oral contraceptives, were incubated with 2 ng lipopolysaccharides (LPS)/ml blood. Quantitation of thromboxane B2 (TxB2) in the resultant plasma revealed a significantly (p less than 0.001) higher generation of TxB2 in men than in women. No sexual differences were observed in thromboplastin activity in unstimulated and LPS stimulated monocytes. Addition of liposomes together with LPS enhanced the synthesis of thromboplastin 2-10 fold and unveiled a higher synthesis of thromboplastin among men. No differences were observed in TxB2 and thromboplastin synthesis in blood collected from females or females using oral contraceptives. A significant correlation between TxB2 and the thromboplastin activity exists within the male (r = 0.46, p = 0.003) and the oral contraceptive (r = 0.57, p = 0.016) group after exposure to LPS. This study suggests that males exposed to LPS may generate more thromboxane A2 than females and thus be at higher risk of developing thrombosis.

Adult↗
PubMed1989

Effects of dietary supplementation with cod liver oil on monocyte thromboplastin synthesis, coagulation and fibrinolysis.

In a controlled trial 40 healthy persons (20 men and 20 women) were tested before and after a daily supplement with 25 ml cod liver oil for 8 weeks. The diet increased the eicosapentaenoic acid (20:5 n-3) content in serum and monocytes four- to five-fold whereas the arachidonic acid (20:4 n-6) content decreased 10-20% in both serum and monocytes. Stimulation of blood with a low concentration of lipopolysaccharides (LPS) revealed a 40% suppression of LPS-induced thromboplastin synthesis in the monocytes after 8 weeks of CLO intake. In the same LPS stimulation system, men were found to generate significantly more thromboxane B2 than women (4.9 ng ml-1 versus 3.4 ng ml-1). After the CLO supplementation for 8 weeks the thromboxane B2 was reduced by a mean of 70% in women and 60% in men. Factor VII and fibrinogen appeared to be unaltered by CLO intake. Determination of whole blood clot lysis time and tissue plasminogen activator (t-PA) did not indicate any significant influence of n-3 fatty acids on fibrinolysis.

Adult↗
PubMed1989

Effect of steroids during Escherichia coli endotoxinaemia in rabbits.

A study was carried out on the effect of high doses of methylprednisolone to rabbits in combination with or after challenging them with Escherichia coli endotoxin. The animals given steroids simultaneously with the endotoxin or 2-6 h thereafter all had significantly higher white cell counts 24 h after endotoxin infusion. A second dose of endotoxin given 24 h after the first caused a rapid fall in white cell count, and no difference between the groups could then be observed 2 h later. The most striking effect was observed when methylprednisolone was administered simultaneously with the endotoxin. This caused a suppression of the clearance of endotoxin from the circulation, and this in turn could probably account for some newly synthesized thromboplastin expressed by the circulating monocytes. Furthermore, monocyte activation appears to be significantly higher in the animals receiving steroids than in the controls when the animals are subjected to two doses of endotoxin injections 24 h apart. Thus, high doses of methylprednisolone cannot be seen to have any beneficial effect as judged from the parameters tested in the present study.

Animals↗
PubMed1989

Effects of two triphasic oral contraceptives containing ethinylestradiol plus levonorgestrel or gestodene on blood coagulation and fibrinolysis.

The hemostatic effects of a new triphasic oral contraceptive combination containing ethinylestradiol and the new progestogen gestodene were compared with those of a triphasic combination of ethinylestradiol and levonorgestrel. A total of 19 women who did not use any kind of hormonal contraception 3 months prior to the study were recorded. The following parameters were measured: whole blood clotting time (WBCT), whole blood clot lysis time, fibrinogen, antithrombin III, factors V, VII and VIII. Blood samples were taken before treatment and in cycles 1, 3 and 6. A significant shortening of WBCT was observed in cycle 3 and 6 in both groups and also in cycle 1 in the gestodene group. This may indicate an increased sensitivity for activation of platelets, since the assay appears to be quite sensitive to this process. In the other parameters tested there were no significant changes except for a slight increase in plasma fibrinogen in cycle 1 in the gestodene group.

Adult↗
PubMed1989

Fatty acids, platelets and monocytes. Something to do with atherogenesis.

A remarkable variation in monocyte activation among individuals was observed when blood from different people was incubated with lipopolysaccharides. To elucidate this phenomenon, we studied intracellular signals associated with monocyte activation. This was done by measuring induced thromboplastin synthesis. An inhibitor of phospholipase A2 blocked the lipopolysaccharide induced synthesis of thromboplastin. Thus, release of arachidonic acid (20: 4) seemed to be necessary to activate the monocytes. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, had no effect on the monocyte activation in subjects with a low response to lipopolysaccharides (low responders); this contrasted with nearly 80% inhibition in individuals with very sensitive cells (high responders). Taking aspirin raised monocyte activation by an average of 50%, this was caused by the effect of aspirin on the platelets. Platelets enhanced the lipopolysaccharide activation of monocytes 2-3 fold. The high response phenomenon was partially due to platelets. When platelets in the blood of high responders were substituted with platelets from low responders, the monocyte activation fell by up to 70%. Fatty acids seemed to play a central role in the activation of monocytes. Intake of cod liver resulted in significant reduction of induced thromboplastin synthesis. It is suggested that those who are high responders may be more susceptible to developing atherosclerosis.

Arteriosclerosis↗
PubMed1989

Effect of strenuous exercise on blood monocytes and their relation to coagulation.

Changes were explored in the behavior of circulating monocytes and their potential association with the activation of the coagulation system as assessed following strenuous exercise. Twelve men and nine women from the Norwegian national cross country skiing team and 19 men and six women from a level just below that of the national team were studied before and after ski race competition. Mononuclear cells were isolated after incubation of heparinized blood with lipopolysaccharides (LPS; 3 ng.ml-1) for 2 h. After a 50 km race for men, the specific thromboplastin activity of the stimulated monocytes rose from 3.5 x 10(-3)/10(6) cells to 21.4 x 10(-3)/10(6) cells. This probably reflects the mobilization of a new population of monocytes that are more sensitive to such stimuli. Resting top-athlete skiers had monocytes which were significantly less responsive to the LPS stimulus compared to nontrained people. There was an inverse correlation of plasma factor VII and the monocyte responsiveness to in vitro stimulation (r = 0.814; P less than 0.002) from blood drawn after a race. Furthermore, factor VII was significantly reduced after a 50 km race, and a modest decline in the fibrinogen level was also observed (P less than 0.05). It is concluded that endurance ski racing causes white cell mobilization and more active white cells that may induce activation of the coagulation system and account for the involvement of factor VII and fibrinogen.

Blood Coagulation Factors↗
PubMed1988

Increased plasma levels of endotoxin and corresponding changes in circulatory performance in a porcine sepsis model: the effect of antibiotic administration.

Changes in endotoxin levels and cardiovascular performance during antibiotic therapy in septicemia were investigated in a porcine model. One group of animals (n = 9) received gentamicin 2 mg/kg intravenously infusion two hours after induction of sepsis with live E. coli bacteria. Another group (n = 7) served as non-treated septic controls. Plasma-levels of endotoxin increased significantly after antibiotic administration from 0.26 +/- 0.02 ng/ml before treatment (0 hrs), to 1.1 +/- 0.3 ng/ml after two hours (p less than 0.01) and 2.1 +/- 0.98 ng/ml four hours after treatment (p less than 0.01). In the control group no significant increase occurred in the observation period. No difference could be demonstrated between the groups with regard to the number of live bacteria in blood, either before or after treatment. When the data from all the animals were taken together for the first two hours following antibiotic administration a significant negative correlation (p less than 0.05) was demonstrated between changes in endotoxin levels and cardiac output. This correlation was significant for animals in which the levels of endotoxin increased above 0.5 ng/ml (p less than 0.05). The present study indicates that endotoxin is liberated after antibiotic administration during bacteremia, and that this increase correlates with cardiac performance.

Animals↗
PubMed1987

Platelet storage lesion: formation of platelet fragments with platelet factor 3 activity.

Certain samples of stored platelet concentrates exhibited marked platelet factor 3 activity. This activity was associated almost completely with platelet fragments formed during storage. Platelet concentrates containing high levels of these fragments and hence high platelet factor 3 activity were characterized after storage by alkaline plasma pH values, high levels of extracellular lactate dehydrogenase activity and relatively low cell counts.

Blood Platelets↗
PubMed1987

Experimental gram-negative septicemia: thromboplastin generation in mononuclear phagocytes from different anatomical sites.

Rats were subjected to gram-negative septicemia induced by cecal perforation or were sham-operated. Thromboplastin values increased in blood monocytes (40-fold), peritoneal macrophages (115-fold) pleural macrophages (5-fold), splenic macrophages (3-fold), and lung alveolar macrophages (1.4-fold) in septic animals as compared to controls. In septic animals disseminated intravascular coagulation was evidenced by a significant (p less than 0.05) fall in fibrinogen, factor VII, X and platelets. A simultaneous and significant (p less than 0.05) decrease in thromboplastin content of tissue-specimens from lung and spleen was observed in rats with septicemia, whereas increased thromboplastin values were demonstrated in tissue-samples from cecum - the infectious focus. This might reflect mobilization of mononuclear phagocytes in favour of the site of infection.

Animals↗
PubMed1987

The development of monospecific antibodies against human thromboplastin apoprotein (apoprotein III) and their application in the immunocytochemical detection of the antigen in blood cells.

Human thromboplastin apoprotein (apoprotein III) purified by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) was purified a further 2-4 fold by PAGE in the presence of digitonin. Subsequent line immunoelectrophoresis of the protein revealed several lines, only one of which contained inhibitory antibodies. New inhibitory antibodies which were raised by using this particular line to immunize rabbits produced only a single line in immunoelectrophoresis of apoprotein III, with precipitated inhibitory antibodies being present only in the line. When these antibodies were used in electroblot immunobinding studies of crude thromboplastin after SDS-PAGE staining was found mainly in a single band of MW about 50,000, but also to some extent in immunologically related higher MW material. Prior deglycosylation of the thromboplastin using trinitrobenzenesulfonic acid resulted in a shift of the bulk of the main band representing an apparent MW reduction of 16%, and a corresponding shift in the position of protein with the capacity to bind inhibitory antibodies. Besides being a good criterion of specificity of the antibodies this also suggests that non-carbohydrate parts of apoprotein III may be involved in the interaction with Factor VII. Immunoperoxidase staining of unstimulated or endotoxin stimulated blood cells using the antibodies revealed the presence of significant amounts of apoprotein III only in stimulated monocytes, apparently available on the surface of the cells since it was detectable also by preembedding staining of fixed cells in suspension. The result is strong evidence that apoprotein III is synthesized de novo in monocytes upon endotoxin stimulation.

Antibodies↗
PubMed1987

[Contrast medium reaction to iohexol (Omnipaque) with monocyte activation demonstrated in vivo].

A contrast reaction to the intravenous injection of the non-ionic contrast medium iohexol (Omnipaque) is reported. The symptoms developed several hours after the injection and at first were not recognised as being due to the contrast. The reaction could be reproduced under controlled conditions and was associated with a significant rise in thromboplastin synthesis in circulating monocytes, a sign of marked cellular activation.

Adult↗
PubMed1987

Abdominal operations: effect on subsequent experimental faecal peritonitis.

Rats were subjected to laparotomy, anaesthesia only (controls), laparotomy plus 1-cm-segment ileum isolation, or no treatment (controls) and were challenged with endogenous faecal peritonitis 1 and 2 weeks later, respectively. Survival rates were 40% for the laparotomy group and 100% for the ileum isolation group, whereas all controls died. The number of peritoneal leucocytes, particularly macrophages and neutrophils, was significantly (p less than 0.05) higher in the laparotomy group than in the control group. The data show that abdominal operations alone--and especially in combination with a minor infectious challenge--entail an increased tolerance to subsequent peritonitis, possibly mediated by the previously stimulated and sensitized leucocytes.

Abdomen↗