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Biomedical subjects

O Hetland

Publications and source records attributed to O Hetland.

At least 19 recordsLinked to original sources
PubMed1995

Improvement of serum lipids and blood pressure during intervention with n-3 fatty acids was not associated with changes in insulin levels in subjects with combined hyperlipidaemia.

OBJECTIVES: To investigate the effect of an omega-3 fatty acid concentrate K85 on serum lipids, lipoproteins, insulin metabolism and blood pressure in subjects with combined hyperlipidaemia. DESIGN: After a run-in dietary period of 10 weeks, subjects were randomly allocated to receive either encapsulated K85 (n = 28) or corn oil (n = 29). The intervention was double-blind. SETTING: An outpatient centre in Stavanger, Norway. SUBJECTS: Fifty-seven of 141 individuals, who, after the run-in period continued to meet the inclusion criteria: serum triglycerides of > or = 2.0 mmol L-1 and total serum cholesterol of > or = 6.0 mmol L-1. INTERVENTION: Encapsulated K85, containing 85% eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA), or corn oil, both administered in a daily dose of 4 g for 12 weeks. MAIN OUTCOME MEASURES: Change in metabolic and haemodynamic parameters related to intervention. RESULTS: Serum EPA and DHA increased significantly in the K85 group during the treatment period. The body-mass index remained unchanged. A 28% reduction in serum triglycerides was noted in the K85 group from the first 4 weeks. Total serum cholesterol was significantly reduced with both regimens. Serum high-density lipoprotein cholesterol increased significantly during the first 8 weeks in the K85 group. Significant reductions in systolic and diastolic blood pressures were noted in subjects on K85. The treatment did not affect serum glucose, plasma insulin and proinsulin levels. Insulin:glucose and proinsulin:glucose ratios remained unchanged. CONCLUSIONS: The atherogenic risk profile was improved with K85 in subjects with combined hyperlipidaemia, but n-3 fatty acids supplementation did not affect glucose/insulin homeostasis.

Adult↗
PubMed1990

Procoagulant (thromboplastin) activity in human bronchoalveolar lavage fluids is derived from alveolar macrophages.

Fibrin deposition in the alveolar space and the lung interstitium is a prominent feature of many types of inflammatory pulmonary diseases. Cells of the monocyte/macrophage line are the primary cells supplying procoagulant activity in inflammatory lesions. In the present study we found that both lung alveolar macrophages (LAM) and bronchoalveolar lavage fluids (BALF) from humans contained procoagulant activities. The procoagulant in BALF was associated with membrane vesicles which sedimented at 100,000 g for 1 h. By electron microscopy the BALF ultrasediment was seen to consist almost exclusively of membrane material and this was confirmed by monitoring the content of different marker enzymes for specific subcellular structures. Using macrophage membrane markers, at least part of the BALF-ultrasediment was shown to be derived from LAM. On the basis of phospholipase C sensitivity, antibody neutralization and the site of action of the procoagulant in the sequential activation of coagulation factors, both the LAM-associated and the BALF-associated procoagulant activity was identified as thromboplastin (tissue factor) or thromboplastin-factor VII complexes. This suggests that alveolar macrophages and the LAM-derived thromboplastin-containing microvesicles may contribute to intraalveolar and interstitial fibrin deposition in vivo and probably also have consequences for the development of pulmonary fibrosis.

Bronchoalveolar Lavage Fluid↗
PubMed1988

Effects of phospholipase C, a tissue thromboplastin inhibitor, on pulmonary microembolism after missile injury of the limb.

Tissue thromboplastin probably plays an important role in the development of post-traumatic pulmonary microembolism. Infusion of purified human tissue thromboplastin in animals resulted in an intravascular coagulation and respiratory insufficiency. This could be inhibited by previous infusion of phospholipase C (PLC) from Bacillus cereus. We have studied the effects of PLC infusion on the course of post-traumatic pulmonary microembolism, induced by a high-energy (c. 700 J) missile trauma to the hind legs of pigs. The trauma resulted in a major muscular injury and an indirect femoral fracture. Untreated pigs developed intrapulmonary microemboli. The degree of microembolism in the lungs was measured quantitatively by external detection over the right lung of radiolabeled platelets and fibrin. Infusion of 80 micrograms PLC/kg/hour resulted in an accumulation of blood PLC associated with toxic reaction leading to increasing tachycardia and circulatory collapse after 10 hours. PLC infusion of 20 micrograms/kg/hour did not inhibit the pulmonary microembolism. A PLC-dose in between, viz. 40-50 micrograms/kg/hour, proved to efficiently inhibit most of the microembolism during the infusion period. Cessation of PLC infusion after 24 hours was accompanied by a later increase in pulmonary trapping of platelets and fibrin and decreases in paO2. Concomitantly there were opacities seen on chest X-rays. The results show that tissue thromboplastin is an important etiologic factor in post-traumatic pulmonary microembolism and that inhibition with phospholipase C can be of value in the prophylaxis of the syndrome.

Animals↗
PubMed1985

Thromboplastin (tissue factor) in plasma membranes of human monocytes.

The synthesis of thromboplastin, a potent trigger of blood coagulation, can be induced in human peripheral blood monocytes. Indirect evidence suggests that newly synthesized thromboplastin becomes in part available on the cell surface. We have attempted to study the localization and availability of thromboplastin more directly by isolating plasma membranes from isolated human peripheral blood monocytes. The specific activities of the plasma membrane markers increased 16-22-fold in these preparations with a recovery of about 15%. The contamination by mitochondria, lysosomes, nuclei and endoplasmic reticulum was low as estimated by marker enzymes and electron microscopy. In both unstimulated and stimulated monocytes thromboplastin was largely recovered in this plasma membrane fraction, providing direct evidence for its membrane localization. Phospholipase C (E.C. 3.1.4.3) is a potent inactivator of thromboplastin through its hydrolysis of the phospholipids necessary for thromboplastin activity [Otnaess, Prydz, Bjørklid & Berre (1972) Eur. J. Biochem. 27, 238-243]. About 70% of the total membrane thromboplastin activity was inactivated when whole cells were treated with phospholipase C and the membranes subsequently isolated. Following stimulation to induce thromboplastin synthesis, the plasma membranes showed a shift in their relative content of phosphatidylcholine and phosphatidylethanolamine consistent with a transmethylation process.

Cell Membrane↗
PubMed1985

Inhibitory effect of 3-deazaadenosine on the thromboplastin response of stimulated human monocytes.

Immune complexes (IC), 12-O-tetradecanoylphorbol-13-acetate (TPA), endotoxin (LPS) and phytohaemagglutinin (PHA) induce thromboplastin activity in human peripheral blood monocytes. In the presence of transmethylation inhibitors 3-deazaadenosine (DZA) and homocysteine a dose-dependent inhibition of the thromboplastin response reaching about 60 per cent was observed, when IC, LPS or PHA was used as the stimulant. TPA-induced thromboplastin synthesis was more resistant (maximum 20 per cent inhibition).

Dose-Response Relationship, Drug↗
PubMed1983

Monocytes and platelets share the glycoproteins IIb and IIIa that are absent from both cells in Glanzmann's thrombasthenia type I.

By means of an antiserum specific to the complex of the platelet membrane glycoproteins IIb and IIIa we demonstrate here that monocytes and purified monocyte membranes share these glycoproteins with platelets. The monocyte glycoprotein IIb-IIIa complex showed complete immunological identity with the platelet counterpart and, furthermore, dissociated after EDTA treatment exactly as did the platelet complex. In Glanzmann's thrombasthenia type I, monocytes as well as platelets lack this antigen completely.

Antigens, Surface↗
PubMed1983

Comparison of protein and lipid composition of the human platelet alpha-granule membranes and glycerol lysis membranes.

Platelet glycerol lysis membranes and alpha-granule membranes were compared with respect to protein and lipid composition. Crossed immunoelectrophoresis using antibodies against whole platelets, and sodium dodecyl sulphate polyacrylamide gel electrophoresis, revealed the presence of the glycoproteins IIb and IIIa, myosin and an antigen termed G4 in both membrane fractions. The glycoproteins Ia, Ib and IIIb, in addition to beta 2-microglobulin and actin, appeared specific for the glycerol lysis membranes, whereas two antigens, termed G8 and G18, were observed only in the alpha-granule membranes. The localization of glycoprotein IIa was inconclusive. Comparison with the surface-located proteins revealed that the glycerol lysis membranes represented a reasonable approximation to a plasma membrane preparation. Radioactively labelled immunoprecipitates obtained after crossed immunoelectrophoresis of 125I-labelled platelets were cut out and applied to sodium dodecyl sulphate electrophoresis on polyacrylamide slab gels. Autoradiography of the dried gels revealed that antigen G4 represented a protein with an average molecular weight of 146 000 in its unreduced state and 132 000 in its reduced state. Antigen G18 represented a protein of molecular weight 130 000-135 000 in the reduced as well as unreduced state. Quantitation of protein and lipids showed that the alpha-granule membranes contained about one-third as much cholesterol and 2-times as much protein in relation to phospholipids as compared to the glycerol lysis membranes. No significant difference between the two membrane preparations was found as regards the composition of their phospholipids.

Antigens↗
PubMed1983

Intravenous injections of tissue thromboplastin and phospholipase C in rabbits.

Previous experiments (Gollub et al. [10]. Giercksky et al.) have shown that phospholipase C (PLC) has a protective effect on rats and rabbits receiving thromboplastin infusions. As a step towards the possible use of PLC in humans, we have investigated further the use of PLC in rabbits. Infusions of human or rabbit thromboplastin caused a rapid fall in factors V and VIII. LD50 for our standard human thromboplastin preparation was estimated to be 1.5--1.8 ml/kg. Highly purified PLC was given as an intravenous bolus immediately before thromboplastin. No improvement of survival and only a slight difference in factors V and VIII were observed, in contrast to earlier observations in the rat. This may in part be due to differences in the susceptibility to PLC of the thromboplastins used. PLC was also more toxic in rabbits than in rats.

Animals↗
PubMed1983

The effect of phospholipase C in sheep.

Based on earlier studies in rats, phospholipase C (PLC) seemed to be a very promising prophylactic agent for certain types of thrombo-embolic disease. Recent studies in rabbits have, however, demonstrated that phospholipase C is more toxic than expected from the previous data. To gain more knowledge about its toxicity in larger animals we have studied its effect in sheep. Estimated LD50 for the enzyme in sheep was between 0.4 and 0.2 mg PLC/kg given as a 23 min infusion and below 0.2 mg/kg given as a bolus. Cellular necrosis was a common feature in several tissues of sheep dying from PLC. This explained the pulmonary oedema, decreased oxygen tension and renal failure with haematuria, proteinuria and glucosuria which occurred. PLC was probably filtered out in the glomeruli and totally reabsorbed in the tubuli until they were destroyed by PLC. An increase in different plasma enzymes suggested that PLC exerted a toxic effect on both muscle cells and hepatocytes. The blood glucose level remained about 20% lower in the PLC-treated animals than in the controls for more than 2 weeks. Pulmonary oedema and renal failure were the probable causes of death.

Animals↗
PubMed1982

In vitro effect of phospholipase C from Bacillus cereus on tissue thromboplastin from different species.

Purified phospholipase C from Bacillus cereus caused a significant loss in the procoagulant activity of thromboplastin preparations from man, rabbit, sheep, cow, rat and mouse. However, marked differences were observed with respect to the degree of inactivation. Rat, mouse, bovine and one type of rabbit preparations (prepared from acetone powdered brain) were markedly more sensitive to attack by phospholipase C than were preparations of human, sheep and standard rabbit preparations. The relative amounts of the individual phospholipids in thromboplastin preparations showed only minor variations among the species. The effect of phospholipase C on each of these phospholipids in the various thromboplastin preparations showed some significant differences.

Animals↗
PubMed1982

Synthesis of thromboplastin protein by a murine macrophage-like cell line.

The established murine macrophage cell line J-774.1 responds to endotoxin with synthesis of thromboplastin apoprotein. The response develops in the absence of added lymphocytes and there is no increased responsiveness in cocultures of J-774.1 cells and BALB/c lymphocytes. J-774.1 cells therefore do not depend on lymphocyte cooperation for their response to endotoxin.

Animals↗
PubMed1982

Phospholipase C from Bacillus cereus has sphingomyelinase activity.

Purified, electrophoretically homogeneous phospholipase C (PLC) preparations can be separated into two peaks by isoelectric focusing in sucrose gradients. The main peak has an isoelectric pH of 6.6-6.8 and contains two Zn2+ per molecule. The more acid peak (isoelectric pH about 6.2) contains about one Zn2+ per molecule and has a markedly reduced specific activity which can be raised by adding Zn2+. The purified enzyme has a low sphingomyelinase activity which coincides completely with the lecithinase activity in fractions from isoelectric focusing. The sphingomyelinase activity was greatly enhanced by substitution of Co2+ for Zn2+ but remained essentially unaltered when the levels of Ca2+ and Mg2+ were changed. These findings provide evidence that the sphingomyelinase activity is a true endogenous activity of PLC and not caused by contaminating sphingomyelinase.

Bacillus cereus↗
PubMed1982

Toxicity of phospholipase C in rabbits.

Tissue thromboplastin is the most potent physiological trigger of blood coagulation and is probably involved in the pathogenesis of several forms of intravascular coagulation. Phospholipase C from Bacillus cereus is an effective inhibitor of thromboplastin. As part of an investigation into the possible use of phospholipase C as a therapeutic or prophylactic agent in thrombosis and other forms of intravascular coagulation, we have previously studied its effect in rats. We now report on the toxicity in rabbits (along with some data on cats and monkeys). Estimated LD50 for rabbits was about 0.45-0.65 mg/kg (as compared to 1.70 mg/kg for rats). No respiratory or circulatory changes were observed, but phospholipase C caused a significant increase of several plasma enzymes in rabbits.

Acid-Base Equilibrium↗
PubMed1980

Assessment of cerebral injury with spinal fluid creatine kinase (CSF-CK) in patients after cardiac resuscitation.

Serial determinations of creatine kinase in cerebrospinal fluid (CSF) were made in eighty-two patients, that were comatose after cardiac resuscitation because of ventricular fibrillation. In all patients who remained unconscious creatine kinase (CSF-CK) increased from less than 2 U/L to 11 U/L or more with maximum CSF-CK averaging 53 +/- 6 U/L 48-72h after resuscitation. In patients who recovered consciousness maximum CSF-CK activity never exceeded 11 U/L. However, maximum CSF-CK activity between 5 and 11 U/L was always associated with some permanent cerebral dysfunction. Complete cerebral restitution was only observed when maximum CSF-CK was 5 U/L or less. In some patients a maximum CK activity of 4 U/L was associated with depressed memory functions. The blood-brain barrier was impermeable to CK as evidenced by isoenzyme analysis and lack of correlation between CK activity in CSF and peripheral blood. CSF-pressure rose slightly to 217 +/- 11 mmH2O in patients with CSF-CK above 10 U/L and to 197 +/- 15 mmH2O when CSF-CK was below 5 U/L. The results indicate that high CSF-CK activity, whether appearing early or late after successful cardiac resuscitation, effectively predicts an unfavourable outcome of global cerebral ischemia. No rise in CSF-CK was always indicative of full cerebral recovery.

Aged↗
PubMed1978

Plasma hypoxanthine levels in pigs during acute hypoxemia. A correlation between lactate and base deficit concentrations.

Tissue hypoxia was induced in pigs by artificial ventilation with 6% O2 in N2 for 18 min. Base deficit, lactate and hypoxanthine increased linearily during this period, and were significantly higher than initial values in the course of 6 min of hypoxemia. High correlation coefficients between hypoxanthine and lactate (mean 0.98) and between hypoxanthine and base deficit (mean 0.98) were found. During the recovery period when the animals were ventilated with air, high correlation coefficients between lactate and hypoxanthine (mean 0.75) and between base deficit and hypoxanthine (mean 0.83) were also found. It is concluded that plasma hypoxanthine concentrations should be used to assess tissue hypoxia also in clinical situations.

Animals↗