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B Osterud

Publications and source records attributed to B Osterud.

At least 55 records · Page 3Linked to original sources

Thromboxane production in the blood of women increases after menopause whereas tumor necrosis factor is reduced in women compared with men.

Previously we have shown that incubation of heparinized blood with a low dose of lipopolysaccharides (5 ng/ml) resulted in a 60% higher generation of TxB2 in the blood of young men as compared with that of young women. In the present study, we investigated a group consisting of 38 healthy men and 38 healthy postmenopausal women aged 50-73 years with no drug use and no known chronic disease. In contrast to our earlier observation that young men produce more TxB2 than young women, no significant difference was observed between the men and women when all the participants above 50 years of age were included (5.7 +/- 0.6 ng/l for men versus 5.2 +/- 0.7 ng/l for women). However, a strong correlation was found with simple regression analysis when increasing TxB2 generation was compared with years after menopause (P < 0.0001). No such correlation was observed for increasing age of men and their TxB2 production. The LPS stimulation system of whole blood was also used to evaluate the production of tumor necrosis factor (TNF-alpha) in older people. Men were found to generate 60% more TNF-alpha than women, but no correlation was found between increasing age of women and TNF-alpha production as observed with TxB2. Risk factors such as SDS-cholesterol, fibrinogen and factor VII were the same in men and women, whereas total cholesterol was higher in women than in men (P < 0.05). Since TxA2 is known to be a mediator of atherosclerotic-induced lesions and TNF-alpha is a well-established indicator of inflammatory reactions, we propose that the reduced production of TxB2 and TNF-alpha in women in our model system may partially explain the lower incidence of atherosclerosis in women as compared with men, and the phenomenon of increased incidence of this disease after menopause.

Aged↗

Enhanced sensitivity of the extrinsic coagulation system during ovarian stimulation for in-vitro fertilization.

The tissue factor activity in blood monocytes was investigated during ovarian stimulation for in-vitro fertilization (IVF) in 13 women. Blood samples were taken prior to hormonal stimulation (days 2-3 of the menstrual cycle, median serum oestradiol concentration 70 pmol/l) and the day after ovulation induction with human chorionic gonadotrophin (days 11-13, median serum oestradiol concentration 6270 pmol/l). The tissue factor activity in unstimulated monocytes and factor VII concentration were unchanged during the treatment. However, the tissue factor activity in lipopolysaccharide-stimulated monocytes was on average more than twice as high after stimulation (P < 0.02). A positive correlation was found between the tissue factor activity and the serum concentration of oestradiol (r = 0.514, P < 0.02). The tumour necrosis factor (TNF)-alpha increased during ovarian stimulation (P = 0.05), and there was a positive correlation between the change in TNF-alpha and the change in tissue factor activity (r = 0.663, P < 0.05). Our results indicate an enhanced sensitivity of the extrinsic coagulation system during IVF treatment since more tissue factor is available upon stimulation. It is suggested that this may be important in thrombotic situations. Further studies are necessary to elucidate the mechanism behind this response.

Adult↗

Interruption of vascular thrombus formation and vascular lesion formation by dietary n-3 fatty acids in fish oil in nonhuman primates.

BACKGROUND: Because of discrepant claims regarding the relative biological effects of n-3 fatty acids (n-3FAs), we have concurrently measured the effects of dietary n-3FAs on blood and vascular lipid composition, hemostatic function, blood thrombotic responses, vascular thrombus formation, and vascular lesion formation in baboons. METHODS AND RESULTS: Dietary n-3FAs displaced n-6FAs in plasma, platelets, blood vessels, and corresponding urinary eicosanoid metabolites (p < 0.01 in all cases) within weeks after initiation of a semipurified diet containing 1 g/kg per day n-3FA-ethyl ester concentrate (composed of two thirds eicosapentanoic acid and one third docosahexanoic acid). Coincidentally, platelet hemostatic function became minimally impaired (template bleeding times prolonged from 4.3 +/- 0.5 minutes to 7.6 +/- 1.3 minutes, p = 0.039); concentrations of collagen producing half-maximal platelet aggregation increased (from 6.4 +/- 2.1 to 8.5 +/- 2.5 micrograms/mL, p = 0.045); and tissue factor expression by endotoxin-stimulated blood monocytes fell (from 6.5 +/- 1.2 to 1.7 +/- 0.14 mU/10(6) cells, p < 0.005). Dietary n-3FAs decreased deposition of platelets onto thrombogenic segments of Dacron vascular graft incorporated into chronic exteriorized femoral arteriovenous (AV) shunts, a thrombotic process resistant to the effects of both aspirin and heparin (111In-labeled platelet deposition decreased from 14.1 +/- 1.4 x 10(9) platelets/5-cm segment at 40-60 minutes with occlusion to 7.5 +/- 0.8 x 10(9) platelets/5-cm segment without occlusion; p < 0.001). Platelet deposition onto segments of endarterectomized homologous normal aorta in the AV shunts of n-3FA-treated animals was similarly reduced (from 4.4 +/- 0.9 to 1.8 +/- 0.4 x 10(9) platelets; p < 0.01). Dietary n-3FAs interrupted vascular thrombus formation at sites of surgical carotid endarterectomy (platelet deposition, 1.5 +/- 0.4 versus 4.4 +/- 1.0 x 10(9) platelets in untreated controls; p < 0.001). Moreover, endarterectomized aortic segments (EASs) from n-3FA-treated donors exhibited little capacity to induce thrombus formation when tested in the AV shunts of control recipient animals (0.24 +/- 0.10 versus 4.4 +/- 0.90 x 10(9) platelets). However, in the converse crossover experiments, EASs from control animals actively accumulated platelets when studied in the AV shunts of n-3FA-treated animals (1.8 +/- 0.4 x 10(9) platelets; p < 0.01 versus n-3FA-treated EASs in shunts of normal animals). Dietary n-3FAs also abolished vascular lesion formation at sites of carotid endarterectomy 6 weeks after surgery (cross-sectional area of neointima 0.048 +/- 0.031 mm2 compared with 0.428 +/- 0.104 mm2 in control arteries; p = 0.010). CONCLUSIONS: In nonhuman primates, dietary n-3FAs in high doses eliminate both vascular thrombus formation and vascular lesion formation after mechanical vascular injury while largely sparing hemostatic function and modestly reducing blood thrombotic responses. These effects are attributed to selective n-3FA-dependent alterations in cellular membrane functions.

Animals↗

Thromboplastin activities and monocytes in the coronary circulation of reperfused human myocardium. No effect of preoperative treatment with n-3 fatty acids.

In a double-blind study 18 patients were randomized to receive a daily dietary supplement of concentrated ethyl ester compound of n-3 fatty acids or placebo (corn oil) for at least 6 weeks before coronary bypass surgery. Three-fold increase of serum eicosapentaenoic acid and 20% reduction of triglyceride levels were found preoperatively in the n-3 group, while the two groups were similar as regards monocyte and platelet counts, mean platelet volume and monocyte activation as expressed by thromboplastin activities. For determination of transcardiac gradients, coronary sinus and aortic blood were sampled preoperatively 5, 10 and 30 minutes after release of the aortic cross-clamp. In both patient groups the monocyte count was lower in coronary sinus than in aortic blood at 5 and 10 minutes, but the differences were not significant. The platelet counts showed no significant change. In vitro stimulation of monocytes, however, evoked significantly (p < 0.05) less thromboplastin activity in coronary sinus blood than in aortic blood at all three sampling times, without significant intergroup difference. The monocytes most sensitive to activation presumably were trapped in the reperfused myocardium, and this sequestration was not hindered by pretreatment with n-3 fatty acids.

Aged↗

Changes in blood cell response following strenuous physical exercise.

The generation of tumour necrosis factor (TNF) and tissue factor activity in lipopolysaccharide (LPS) stimulated blood were studied in 25 healthy subjects before and after physical exercise of different intensities. Of the subjects a group of 9 were athletes who trained once to twice every day of the week, a second group of 8 exercised 3-7 times a week, and a third group of 8 exercised 4-5 times a month. The production of TNF in freshly drawn LPS stimulated blood in heparin, drawn from top athletes at rest was significantly lower than in the other subjects. The LPS induced concentrations of TNF-alpha of 2.73 (SEM 1.05) ng.ml-1 in the blood of the top athletes compared to 5.08 (SEM 0.7) ng.ml-1 and 7.6 (SEM 1.6) ng.ml-1, respectively, in the other two groups. The group that trained the least had the highest values. Immediately after exercise, the monocytes appeared to be less responsive to LPS stimulation, as a reduction of 47%-48% was observed in the top athletes and in the other group of well-trained individuals. The group that trained the least, which was also subjected to the least stressful exercise, had a 33% reduction in TNF production. Within 6 h the TNF concentration was back to pre-exercise values. Within 6 h the TNF concentration was back to pre-exercise values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Haematological disorders and lung alveolar macrophage function following total parenteral nutrition in rats.

Alterations in haematological parameters have been reported both clinically and experimentally following administration of total parenteral nutrition (TPN). Fat emulsions also affect function of the mononuclear phagocytic system. We have examined haematological parameters and pulmonary alveolar macrophages in rats fed intravenously with the individual components of TPN; a 20 % fat emulsion (Intralipid) and an amino acid solution (Vamin-Glucos), for 1, 3 and 7 days as a continuous infusion. The control groups were given saline infusion for the same periods of time. Haemoglobin, haematocrit, red blood cells, leukocytes, leukocyte superoxide anion production, leukocyte distribution, platelets and platelet aggregation were measured. Lung lavage fluid was examined for alveolar macrophage concentration and procoagulant activity of macrophages. Several of the animals in the experimental groups developed superior caval vein thrombosis. Both experimental groups developed anaemia after 7 days of infusion. Thrombocytopaenia occurred in both experimental groups after 3 and 7 days of infusion. Platelet aggregation decreased already after 1 day of infusion. We did not observe any alteration in counts, distribution in peripheral blood, or superoxide production of leukocytes. The concentration of alveolar macrophages in the lung lavage fluid increased in the experimental groups. The tissue factor activity of the alveolar macrophages increased in the group receiving Intralipid. Our observations are consistent with a granulomatous inflammation reaction.

Journal Article↗

Increased lipopolysaccharide-induced tissue factor activity and tumour necrosis factor production in monocytes after intake of aspirin: possible role of prostaglandin E2.

To determine how aspirin intake might influence lipopolysaccharide (LPS)-induced tissue factor (TF) activity and tumour necrosis factor (TNF) in human blood monocytes, we collected blood before and at various times after intake of 300 mg aspirin in 25 healthy volunteers. Aspirin intake reduced LPS-induced thromboxane B2 and PGE2 production in whole blood by 50% and 65% respectively, measured 1 h after aspirin intake. Subsequently, a 95% rise in LPS-induced TF activity in monocytes was seen as compared to a 26% rise in TNF. The rise in TF activity was maximal within 1 h after aspirin intake and no further rise was observed 3, 4 or 24 h after aspirin intake. In contrast, TF activity induced by incubating whole blood in the absence of LPS fell rapidly after the intake of aspirin. In separate experiments, a dose-dependent inhibition by PGE2 was observed in LPS-induced TF activity in monocytes. It is proposed that the increased LPS-induced TF activity and TNF production following aspirin intake may be due to suppressed PGE2 formation. The more pronounced rise in TF activity compared to TNF production may be due to an enhancement of the platelet lipoxygenase pathway that has been shown to be important for LPS-induced TF activity in monocytes.

Adult↗

A new protective solution for hypothermic storage of free vein grafts in cardiovascular surgery.

In order to reduce the operative injury of the endothelium in free reversed vein grafts, cultured human endothelial cells were used to test the optimal concentration of the constituents of a flushing solution for improved protection of the endothelium. The following solution proved to be the most suitable when tested at 20 degrees C; mannitol 160 mmol l-1, glucose 15 mmol l-1, NaCl 30 mmol l-1, KHCO3 5 mmol l-1, K2SO4 10 mmol l-1, KH2PO4 4 mmol l-1, MgSO4 20 mmol l-1, CaCl2 1.5 mmol l-1, potassium citrate 1.0 mmol l-1, Pluronic F-68 20 mg l-1, HEPES 4 mmol l-1, HEPES-Na 6 mmol l-1, pH 7.25, osmolality 325 mosmol kg-1 H2O. When endothelial cell injury was measured by a 51Cr-release assay, the new solution protected human endothelial cells in culture during hypothermic incubation better than isotonic NaCl, St Thomas' cardioplegic solution or Krebs-Henseleit's buffer. Transmission and scanning electron microscopy showed that the endothelium of human saphenous vein grafts was well preserved following 6 h of incubation at 20 degrees C with the new solution. As determined by morphometry using scanning electron microscopy, the endothelium of free porcine vein grafts was better preserved after incubation for 2 h at 20 degrees C with the new solution than with either isotonic NaCl (p = 0.02) or diluted, heparinized blood (p = 0.02) as the incubation medium, all cases observed following 2 h of subsequent arterial flow. The present study indicates that the endothelium of free vein grafts can be well protected against hypothermia when the flushing and irrigation fluid has a composition favouring endothelial protection. It appears likely that such treatment of vein grafts will reduce the frequency of vein graft narrowing and occlusion, post-operatively.

Animals↗

Platelet activating factor enhancement of lipopolysaccharide-induced tissue factor activity in monocytes: requirement of platelets and granulocytes.

Incubation of platelet activating factor (PAF) with heparinized blood caused no induction of tissue factor activity in monocytes. However, when PAF was added in addition to weak lipopolysaccharide (LPS), it amplified the LPS effect by 80%. By using separated fresh cell populations resuspended in plasma, PAF was shown to have no enhancing effect when added to mononuclear cells incubated with platelet-rich plasma in the presence of LPS. In contrast, when granulocytes also were included, PAF caused an almost 3-fold increase in LPS-induced tissue factor activity. A PAF antagonist blocked this effect and also reduced LPS-induced tissue factor activity of monocytes in whole blood in a dose-dependent manner. In the recombined cell incubation system, the maximal inhibition by the antagonist was observed in the presence of granulocytes. These data provide evidence for an effect of PAF on granulocytes that probably generates a product that, together with platelets, enhances LPS-induced tissue factor activity in monocytes.

Blood Platelets↗

Influence of a concentrated ethylester compound of n-3 fatty acids on lipids, platelets and coagulation in patients undergoing coronary bypass surgery.

Twenty patients accepted for coronary bypass surgery were randomized to receive either a concentrated ethylester compound of n-3 fatty acids, with a daily dose of 3.15 g of eicosapentaenoic acid (EPA) and 1.89 g of docosahexaenoic acid (DHA), or corn oil (controls) in a double blind study, to evaluate the effect on lipids, platelets and coagulation during the pre- and postoperative phase. Only patients with fasting triglyceride (TG) levels greater than or equal to 1.6 mmol/l at recruitment were eligible. The study was continued for 5 to 6 months. Surgery was usually performed at mid-intervention. Blood samples were collected during morning hours in fasting subjects, just prior to intervention, preoperatively and at final postoperative follow-up. Moreover, blood loss was accurately accounted for postoperatively. A threefold increase (p = 0.0001) of EPA was noted at pre- and postoperative follow-up. TG-levels were reduced 20 and 39%, respectively, in patients on n-3 fatty acids, reaching statistical significance at end of intervention (p = 0.034). TG-levels in controls remained largely unchanged. In patients on n-3 fatty acids, there was a statistically significant increase in serum total cholesterol preoperatively, but this change was no longer present at completion of the study. No significant changes were noted in platelet function, as judged by bleeding time, collagen induced platelet aggregation and release of TxB2 during aggregation. Parameters of extrinsic coagulation, including phospholipase C-sensitive factor VII (PLC-VII) and extrinsic pathway inhibitor (EPI), also remained essentially unchanged in both groups of patients. However, fibrinogen was significantly reduced in controls (p less than 0.05) at end of intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Biphasic changes in leukocytes induced by strenuous exercise.

Seven healthy male volunteers participated in short- (STR, 1.7 km), middle- (MTR, 4.8 km) and long- (LTR, 10.5 km) term runs at a speed close to their maximum. A prompt mobilization of white cells, and lymphocytes in particular, appeared following the exercise. The initial increase in the number of lymphocytes was succeeded by a significant decrease [(P less than 0.03) lymphopenial], which on average was 32%-39% of the pre-exercise values in all groups. A close correlation was found between the initial increase in plasma cortisol concentration after exercise and the subsequent lymphopenia. A modest enhancement in the number of granulocytes immediately after the exercise was accompanied by a comprehensive increase in polymorphonuclear (PMN) elastase concentration accounting for 78.6%, SEM 16.3%, 140.7%, SEM 31.8% and 241.3%, SEM 48.1% in the STR, MTR and LTR groups. No correlation was found between granulocyte number and the plasma PMN elastase concentration. A delayed granulocytosis was noted in all subjects, reaching a peak between 2 and 4 h after the exercise. The magnitude of the granulocytosis varied among subjects and peak values of the number of circulating granulocytes were found to be 5.7 x 10(9) cells.l-1, SEM 0.5, 6.7 x 10(9) cells.l-1, SEM 0.6 and 8.8 x 10(9) cells.l-1, SEM 0.5 in STR, MTR and LTR respectively, whereas the mean baseline value was 3.6 x 10(9) cells.l-1, SEM 0.4. The neutrophilic granulocytosis was not accompanied by a corresponding enhancement in PMN elastase concentration. The plasma cortisol concentration reached a peak 30 min after exercise and declined below the control level in 4 h. Neither the initial increase, nor the subsequent decrease in plasma cortisol concentration were found to be essential for the magnitude of the delayed leukocytosis.

Adult↗

Does ovarian stimulation for in-vitro fertilization induce a hypercoagulable state?

Effects on blood coagulation and fibrinolytic activity during ovarian stimulation for in-vitro fertilization (IVF) were examined in 12 women. Blood samples were taken prior to hormonal stimulation (days 2-3 of the menstrual cycle, mean serum oestradiol concentration 0.16 nmol/l) and the day after ovulation induction with human chorionic gonadotrophin (HCG) (days 10-12, mean serum oestradiol concentration 5.35 nmol/l). We measured whole blood clotting time, whole blood clot lysis time, plasma fibrinogen, factor VII and antithrombin III. The whole blood clotting time was slightly, but not significantly shortened after ovarian stimulation. A significant rise in plasma fibrinogen (P less than 0.001) and reduction in antithrombin III (P less than 0.001) were observed, whereas no change in factor VII was found. The blood fibrinolytic activity was significantly reduced as evaluated by an increase in the clot lysis time (P less than 0.02). These results indicate that ovarian stimulation for IVF may create a state of hypercoagulability.

Adult↗

Serum enriched with n-3 polyunsaturated fatty acids inhibits procoagulant activity in endothelial cells.

Nine healthy male volunteers (mean age 24.3 years, range 21-27 years) ingested 25 ml cod liver oil (CLO) daily for 8 weeks. Blood samples were collected before and after the intervention period. A slight increase in total serum cholesterol (+ 12.2%, P less than 0.01) and high density lipoprotein cholesterol (+ 16.9%, P less than 0.01) were calculated to have a non-significant effect on the high/low density lipoprotein ratio. Polyunsaturated fatty acids in serum were displaced from the n-6 family to the n-3 family, reflected by an eight-fold increase of the eicosapentaenoic (20:5 n-3)/arachidonic (20:4n-6) acid ratio. Human umbilical vein endothelial cells were grown in a medium to which 30% sterile filtered serum, collected before and after CLO supplementation for 72 h, was added. After 2 h exposure to lipopolysaccharides the thromboplastin activity in endothelial cultures incubated with serum enriched with n-3 fatty acids was 43% lower than in cultures containing serum collected before the intervention (1.86 +/- 0.48 10(-3)/10(6) cells vs 3.26 +/- 0.85 10(-3)/10(6) cells). It is suggested that serum prepared from subjects given n-3 fatty acids may support the thromboresistence of endothelial cells.

Adult↗

Early response in septicemia in newborns and their mothers. Effect of Escherichia coli, Streptococcus agalactiae and tumor necrosis factor on lactoferrin release and the generation of tissue thromboplastin.

Using a whole blood in vitro model, we have investigated the effect of Escherichia coli (E. coli), Streptococcus agalactiae (group B streptococci, GBS) and tumor necrosis factor alpha (TNF) on the generation of lactoferrin (LF), interleukin-1 beta (IL-1) and tissue thromboplastin (TPL) in healthy newborns at term and their mothers. E. coli (at a final concentration of 10(7)/ml) significantly increased the release of LF in whole blood from newborns after 20 as well as 60 min stimulation, and in samples from their mothers after 60 min stimulation. A significant increase in the release of LF was observed in both newborns and their mothers after 20 and 60 min stimulation with TNF (at a final concentration of 1000 pg/ml). A combination of TNF/E. coli or TNF/GBS never gave any significant additional stimulatory effect. After stimulation with E. coli or GBS (both at a final concentration of 10(7)/ml) for 60 min a significant increase in production of TNF and TPL was observed in newborns. In newborns a significant increase in production of TNF and TPL was observed also after 20 min stimulation with E. coli. TNF (at a final concentration of 1000 pg/ml) significantly increased the generation of TPL after 20 and 60 min stimulation in both groups. There was a tendency for a greater release of LF and generation of TNF and TPL in samples from newborns compared with their mothers, but the differences were not statistically significant. E. coli, GBS and TNF had no significant effect on the production of IL-1.

Escherichia coli↗

Formation and persistence of procoagulant and fibrinolytic activities in circulation after strenuous physical exercise.

Seven healthy male volunteers were subjected to exercise of short (STR; 1.7 km), middle (MTR; 4.8 km) and long (LTR; 10.5 km) term runs at a speed close to maximal capacity. Blood samples were drawn before, immediately after exercise and at intervals over the next 10 h. FVIIIR:Ag (von Willebrand factor) rose 2.2-3.2 fold and persisted at higher levels than baseline during the observation time. A spontaneous drop in FVII (p less than 0.03) was found immediately after STR (13.5 +/- 2.5%) and LTR (18.3 +/- 2.4%), whereas only a minor decrease (7.5 +/- 6.5%) occurred in MTR. The procoagulant activity of monocytes isolated from whole blood exposed to LPS showed a striking enhancement in STR and MTR. An immediate enhancement in fibrinolytic activity was found in all groups (p less than 0.03) assessed by increased plasma levels of t-PA and shortened whole blood clot lysis time (WBCLT). The transient shortening of WBCLT was succeeded by a tendency to prolongation of the lysis time. A 45-year old male differed markedly from the others by demonstrating an extreme and consistent prolongation of WBCLT. Thus, it has been speculated that strenuous exercise possibly makes a subject more susceptible to a thrombotic event.

Adult↗

Physical exercise enhances plasma levels of extrinsic pathway inhibitor (EPI).

The risk of cardiovascular complications is reported to be several times higher in severe exercise than in daily activity. EPI-mediated inhibition of factor VIIa/thromboplastin enzymatic activity is believed to be an important modulator of blood coagulation during hemostasis. The plasma concentration of EPI, corrected for changes in plasma volume, was determined in healthy male subjects prior to, immediately after and at various time intervals after strenuous exercise of different duration. A slight, but significant decrease in EPI (7.5 +/- 2.8%, p less than 0.03) was found after a short term run (1.7 km), whereas no significant change was seen after a middle term run (4.8 km). In contrast, we observed a marked increase in EPI after a long term run (20.3 +/- 6.9%, p less than 0.03) and in a second group of athletes participating in the Norwegian championship of 30 km cross country skiing (39.9 +/- 10.3%, p less than 0.02). A peak value was reached 2 h after the run, and after that the curve started to approach baseline values. The rise in EPI might reflect a significant release of EPI from the endothelium that is greater than eventually any consumption. Another explanation for this enhancement in EPI might be that the increase in lipoprotein lipase activity after physical exercise causes a rise in the availability of EPI since EPI is known to be associated with lipoproteins in the circulation. It is hypothesized that mobilization of EPI during extensive physical exercise may suppress activation of the clotting system.

Adult↗

Thromboplastin activity of blood monocytes after total hip replacement.

Thromboplastin activity of monocytes from blood of seven patients with total hip replacement was investigated. At 24 h and 48 h after surgery, thromboplastin activity was significantly increased compared to the activity before surgery. Thromboplastin activity of endotoxin-stimulated monocytes was significantly increased at 24 h after surgery. There were no significant changes in Factor V after surgery, Factor VII was significantly lowered at 24 h after surgery, while Factor VIII and fibrinogen were significantly increased at 72 h after surgery. The results indicate that monocyte thromboplastin may be a thrombogenic factor after total hip replacement surgery.

Aged↗