[Hereditary hemochromatosis and use of genetic tests].
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Genetic Counseling↗
Biomedical subjects
P Kierulf
Publications and source records attributed to P Kierulf.
Replacement of partially hydrogenated soybean oil by palm oil in margarine without unfavorable effects on serum lipoproteins.
We have compared the effects of three different margarines, one based on palm oil (PALM-margarine), one based on partially hydrogenated soybean oil (TRANS-margarine) and one with a high content of polyunsaturated fatty acids (PUFA-margarine), on serum lipids in 27 young women. The main purpose of the study was to test if replacement of trans fatty acids in margarine by palmitic acid results in unfavorable effects on serum lipids. The sum of saturated fatty acids (12:0, 14:0, 16:0) was 36.3% of total fatty acids in the PALM-diet, the same as the sum of saturated (12:0, 14:0, 16:0) (12.5%) and trans (23.1%) fatty acids in the TRANS-diet. This sum was 20.7% in the PUFA-diet. The content of oleic acid was 37.9, 35.2, and 38.6%, respectively, in the three diets, whereas linoleic acid amounted to 16, 13.5, and 27.3%, respectively. Total fat provided 30-31% and the test margarines 26% of total energy in all three diets. The subjects consumed each of the diets for 17 d in a Latin-square crossover design. There were no significant differences in total cholesterol, low density lipoprotein (LDL)-cholesterol and apolipoprotein B (apoB) between the TRANS- and the PALM-diets. High density lipoprotein (HDL)-cholesterol and apoA-1 were significantly higher on the PALM-diet compared to the TRANS-diet whereas the ratio of LDL-cholesterol to HDL-cholesterol was lower, although not significantly (P = 0.077) on the PALM-diet. Total cholesterol, LDL-cholesterol, and apoB were significantly lower on the PUFA-diet compared to the two other diets. HDL-cholesterol was not different on the PALM- and the PUFA-diets but it was significantly lower on the TRANS-diet compared to the PUFA diet. Compared to the PUFA-diet the ratio of LDL- to HDL-cholesterol was higher on both the PALM- and the TRANS-diets whereas apoA-1 was not different. Triglycerides and lipoprotein (a) were not significantly different among the three diets. We concluded that nutritionally, palmitic acid from palm oil may be a reasonable alternative to trans fatty acids from partially hydrogenated soybean oil in margarine if the aim is to avoid trans fatty acids. A palm oil-based margarine is, however, less favorable than one based on a more polyunsaturated vegetable oil.
Adult↗
Effect on plasma lipids and lipoproteins of replacing partially hydrogenated fish oil with vegetable fat in margarine.
We have compared the effects on lipoproteins and haemostatic variables of two hard margarines with similar functional properties, one traditional margarine containing partially hydrogenated fish oil (PHFO), and one experimental margarine based on vegetable oil (VO). Both were all-purpose cooking margarines with nearly identical functional properties. Trans fatty acids from PHFO in the traditional margarine were replaced mostly by saturated, monounsaturated and trans fatty acids of vegetable origin in the new formulation. Both test margarines contained approximately the same amount of cis polyunsaturated fatty acids. Sixteen female normolipidaemic students consumed each diet with the two test margarines for 14 d in random order (crossover design). The amount of fat was 31% energy in the PHFO diet and 32% energy in the VO diet. The test margarines provided approximately 26% energy in both diets. In the PHFO diet 7.8% of the energy was derived from trans fatty acids and 9.2% from saturated fatty acids (12:0, 14:0 and 16:0) while in the VO diet, 1.1% energy was derived from trans fatty acids and 13.3% from saturated fatty acids (12:0, 14:0 and 16:0). The natural content of cholesterol in PHFO was deliberately not balanced by addition of cholesterol to the VO diet, thus the PHFO diet contained 215 mg and the VO diet 86 mg cholesterol per 8.5 MJ. LDL-cholesterol concentration was 19% higher in subjects on the PHFO diet compared with the VO diet (P < 0.01). The ratio LDL-cholesterol:HDL-cholesterol was 12.6% higher in subjects on the PHFO diet compared with the VO diet (P < 0.01). The level of apolipoprotein (apo)A-I was 6% lower in subjects on the PHFO diet compared with the VO diet (P < 0.01). The ratio apoB:apoA-I was 10.4% higher in subjects on the PHFO diet than on the VO diet (P < 0.01). There were no significant differences in total cholesterol, HDL-cholesterol, triacylglycerols, apoB, lipoprotein(a) and haemostatic variables between the diets. Our results demonstrate that PHFO, with its unfavourable effects on plasma lipids, can be replaced by vegetable oils in margarine without appreciable loss of functional properties but with significant improvement in the effects on plasma lipoproteins.
Adult↗
Macrophage tropism: fact or fiction?
Primary HIV-1 isolates can be distinguished by phenotypic qualities such as the ability to productively infect cells of established CD4-positive lines and to induce syncytia in MT-2 cells. Such viral phenotypes have also been reported to confer host cell specificity. It is perceived that primary isolates with the syncytium-inducing phenotype (SI or rapid/high) are T cell tropic and are therefore unable to infect primary cells of the monocyte/macrophage lineage. However, we have consistently found that these isolates are as capable of establishing infection in monocyte-derived macrophages (MDM) as the monocytotropic, non-syncytium-inducing variants (NSI or slow/low). It is known that differentiation, activation, and proliferation of human monocytes are affected by both isolation methods and culture conditions. Therefore, to test whether our inability to discriminate macrophage tropic HIV-1 isolates could be explained by differences in culturing techniques, we isolated monocytes by elutriation or short-term adherence and allowed the cells to mature and differentiate in either the presence or absence of autologous lymphocytes. After removal of nonadherent cells, MDM were infected with a panel of SI and NSI primary HIV-1 isolates. MDM were susceptible to infection by the SI as well as the NSI isolates, regardless of whether or not the cells were allowed to mature in the presence of autologous lymphocytes. However, MDM matured in the presence of autologous lymphocytes replicated HIV-1 isolates (both NSI and SI) to a higher titre than MDM matured in the absence of lymphocytes. In light of these findings and recently published reports on HIV-1 phenotype and chemokine receptor usage we believe that the term macrophage-tropic strains of HIV-1 is no longer appropriate.
Cell Differentiation↗
The effect of highly purified eicosapentaenoic and docosahexaenoic acids on monocyte phagocytosis in man.
The n-3 fatty acids (FA) from marine sources are known to exert antiinflammatory effects on monocyte function. There is still controversy whether n-3 FA may increase the susceptibility to infections. The present study was designed to assess the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on monocyte phagocytosis and respiratory burst activity. Fifty-eight healthy men were randomized to take a daily supplement of 3.8 g highly purified EPA (n = 20), 3.6 g DHA (n = 19), or corn oil (n = 19) for 7 wk. Mononuclear leukocytes were collected, isolated, and cryopreserved prior to and after dietary supplementation. Paired samples were analyzed in the presence of autologous serum in a crossover design. Monocyte phagocytosis and respiratory burst activity were measured by flow cytometry after ingestion of Escherichia coli. Monocytes retained their phagocytic ability and respiratory burst activity after supplementation. No reduction in internalization of bacteria was registered. Dietary n-3 FA and particularly EPA improved bacterial adherence to the monocyte surface. In the crossover experiments, there was an adverse effect of serum enriched with n-3 FA on bacterial adherence. We conclude that monocytes retain their phagocytic potential after supplementation with purified EPA and DHA.
Adult↗
Modification of mononuclear cell function after incubation with albumin-bound unsaturated fatty acids or soybean oil emulsion.
Administration of total parenteral nutrition (TPN) with soybean oil emulsion leads to a linoleic acid enrichment of the plasma membrane that may explain an in vivo activation of mononuclear cells (MNC) seen in our previous studies. Fatty acids from the lipid emulsion may have been accessible to MNC after endocytosis of lipid particles, or by direct uptake of fatty acids after lipoprotein lipase hydrolyzation of the emulsion triglycerides. To resemble the incorporation of fatty acids in vivo, we have modified MNC membrane lipid composition by incubation with different albumin-bound unsaturated fatty acids (UFA) or soybean oil emulsion. After incubation with albumin-bound linoleic and oleic acid, the unstimulated release of superoxide anion was unchanged, while zymosan-stimulated release was 140% (n.s) and 112% (p < 0.05) and phorbol-myristate-acetate (PMA)-stimulated release 148% (p < 0.05) and 124% (p < 0.05) of controls, respectively. Incubation with other UFAs or emulsion did not change superoxide anion release. Unstimulated lymphocyte proliferation increased 3 to 13-fold (p < 0.05) after incubation with all UFAs compared to controls, while UFA incubation did not change phytohemagglutinin (PHA) or PMA-stimulated proliferation. Unstimulated lymphocyte proliferation was decreased after incubation with emulsion, while PHA/PMA-stimulated proliferation was unchanged. Increase in membrane fluidity was detectable only after incubation with emulsion. The increased reactivity may have been caused by changes in the lipid environment surrounding membrane-bound enzymes important for signal transduction through the plasma membrane.
Cells, Cultured↗
Systemic thrombin generation and activity resistant to low molecular weight heparin administered prior to streptokinase in patients with acute myocardial infarction.
One hundred patients were included in a randomized open trial to assess the systemic factor Xa (FXa) and thrombin inhibitory effect as well as the safety profile of low molecular weight heparin (LMWH) given subcutaneously in conjunction with streptokinase (SK) in patients with acute myocardial infarction (MI). The treatment was initiated prior to SK, followed by repeated injections every 12 h for 7 days, using a dose of 150 anti-Xa units per kg body weight. The control group received unfractionated heparin (UFH) 12,500 i.u. subcutaneously every 12 h for 7 days, initiated 4 h after start of SK infusion. All patients received acetylsalicylic acid (ASA) initiated prior to SK. Serial blood samples were collected prior to and during the first 24 h after initiation of SK infusion for determination of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III (TAT) complexes, fibrinopeptide A (FPA) and cardiac enzymes. Bleeding complications and adverse events were carefully accounted for. Infarct characteristics, as judged by creatine kinase MB isoenzyme (CK-MB) and cardiac troponin T (cTnT), were similar in both groups of patients. A comparable transient increase in F1 + 2, TAT and FPA was noted irrespective of heparin regimen. Increased anti-Xa activity in patients given LMWH prior to thrombolytic treatment had no impact on indices of systemic thrombin activation. The incidence of major bleedings was significantly higher in patients receiving LMWH as compared to patients receiving UFH. However, the occurrence of bleedings was modified after reduction of the initial LMWH dose to 100 anti-Xa units per kg body weight. In conclusion, systemic FXa- and thrombin activity following SK-infusion in patients with acute MI was uninfluenced by conjunctive LMWH treatment.
Acute Disease↗
Net inflammatory capacity of human septic shock plasma evaluated by a monocyte-based target cell assay: identification of interleukin-10 as a major functional deactivator of human monocytes.
We have developed a functional assay to study the inflammatory capacity of plasma collected from patients with severe gram-negative septic shock. In this assay, elutriation-purified, cryo-preserved human monocytes from one healthy donor are combined with plasma from patients with severe persistent septic shock for 5 h. Subsequently, the plasma is removed, medium added, and procoagulant activity (PCA) and secretion of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) measured after 18-h incubation. Plasma from 10 patients (6 died) infected with Neisseria meningitidis previously shown to contain high levels of native lipopolysaccharide (LPS) (median 2,700 pg/ml), TNF-alpha, IL-6, IL-8, and complement activation products, had a low net spontaneous inflammatory capacity on the monocytes. The median levels of PCA, TNF-alpha, and IL-6 were 5, 0, and 4%, respectively, of the monocyte activities induced by normal plasma boosted with purified N. meningitidis (Nm)-LPS (2,500 pg/ml; net LPS-boosted capacity, 100%). The levels of PCA, TNF-alpha, and IL-6 obtained with plasma from shock patients were not different from those induced by plasma from 10 meningococcal patients without shock or with plasma from healthy persons. Boosting shock plasma with 2,500 pg/ml Nm-LPS had little effect on the monocyte activities since the median values of PCA, TNF-alpha, and IL-6 revealed a minimal increase from 5, 0, and 4% to 9, 2, and 6%, respectively. The shock plasmas revealed a strong LPS-inhibitory capacity that was largely absent in plasmas from 10 meningococcal patients without shock since the median levels of PCA, TNF-alpha, and IL-6 increased from 5, 0, and 0% to 135, 51, and 73%, respectively, after boosting with 2,500 pg/ml Nm-LPS. The LPS-inhibitory capacity was closely associated with the levels of IL-10. The median levels of IL-10 were 19,000 pg/ml in nine shock patients vs. 22 pg/ml in nine nonshock patients with systemic meningococcal disease. Removal of native IL-10 by immunoprecipitation restored the capacity of plasmas to induce monocyte activation either by native LPS or by boosting with Nm-LPS. IL-4 and TGF-beta were not detected in shock plasmas. In 24 patients with detectable meningococcal LPS ( > 10 pg/ml, 0.1 endotoxin units/ml), the levels of IL-10 were correlated to the levels of LPS (r = 0.79, P < 0.001). IL-10 declined from initiation of antibiotic therapy and paralleled the levels of native LPS. Decreasing levels of IL-10 in serially collected shock plasmas were directly related to increasing monocyte responsiveness after Nm-LPS boosting. These results suggest that IL-10 plays a major role in containing activation of monocytes and possibly other LPS-responsive cells during overwhelming meningococcemia.
Adolescent↗
LPS induced release of IL-1 beta, IL-6, IL-8 and TNF-alpha in EDTA or heparin anticoagulated whole blood from persons with high or low levels of serum HDL.
We have examined the lipopolysaccharide (LPS) induced release of interleukin 1 beta (IL-1 beta), IL-6, IL-8 and tumour necrosis factor alpha (TNF-alpha), in EDTA or heparin anticoagulated whole blood, from persons with high or low levels of high density lipoprotein (HDL), incubated at 37 degrees C for up to 20 h. In general, 100 ng LPS/ml gave two to twenty times higher responses than 1 ng LPS/ml, and heparin ten to hundred times higher than EDTA. The release of IL-8 was significantly higher in persons with high HDL, and was correlated with HDL, and inversely correlated with triglycerides and sCD14. The release of IL-1 beta, IL-6 and TNF-alpha was correlated with total cholesterol at medium doses of LPS (100 ng/ml), and inversely correlated with lipopolysaccharide-binding protein (LBP) at low doses of LPS (1 ng/ml). Serum levels of LBP were higher in persons with HDL, although not significantly. These results show LPS responsiveness of pro-inflammatory cytokines in whole blood from persons with high and low levels of HDL to be different, presumably of importance in inflammation and atherogenesis.
Anticoagulants↗
Inhibition of IL-1 induced tissue factor (TF) synthesis and procoagulant activity (PCA) in purified human monocytes by IL-4, IL-10 and IL-13.
Exposure of monocytes to pro-inflammatory cytokines or lipopolysaccharide (LPS) may induce synthesis and expression of tissue factor (TF). In this paper we have focused on the induction of TF-activity in human monocytes by the pro-inflammatory cytokines recombinant human interleukin 1 (rhIL-1 alpha) (rhIL-1 beta) (rhIL-6) and human tumour necrosis factor alpha (rhTNF-alpha), measured as procoagulant activity (PCA) in a microtitre plate-based clot assay. In addition we have studied the modulation of IL-1 alpha/beta induced TF-mRNA and PCA by rhIL-4, rhIL-10 and rhIL13. IL-1 alpha and IL-1 beta induced a concentration dependent increase in TF-activity. Neither IL-6 nor TNF-alpha gave rise to procoagulant activity at the concentrations tested (0.2-20 ng/ml). IL-4, IL-10 and IL-13, all effectively diminished IL-1 alpha/beta induced PCA, shown at the protein- and at the mRNA-level, while cell viability was unaffected. These results add to the previously demonstrated role of IL-4 and IL-10 as inhibitors of LPS-induced TF-activity, showing that these anti-inflammatory cytokines are not specific for LPS-activation but interfere with other stimulating substances such as IL-1, which may be involved in diseases where LPS is not present.
Blood Coagulation Factors↗
Centrifugal pump and heparin coating improves cardiopulmonary bypass biocompatibility.
BACKGROUND: Centrifugal pumps are being used increasingly for short-term extracorporeal circulation purposes such as during heart operations. Whether the centrifugal pump improves the cardiopulmonary bypass biocompatibility has not been fully documented. METHODS: A roller pump (n = 20) was compared in vivo with a centrifugal pump (n = 20) in groups of patients in which cardiopulmonary bypass circuits that were either totally heparin coated (Carmeda BioActive Surface; n = 20) or uncoated (n = 20) were used. We expected the heparin coating to attenuate blood activation, thus possibly making the comparison of the two pumps easier with respect to their different blood activation potentials. Samples of blood plasma, obtained during cardiopulmonary bypass from low-risk coronary artery bypass grafting patients, were analyzed for hemolysis (plasma haemoglobin), complement activation (C3bc and the terminal complement complex), a complement lytic inhibitor (vitronectin), coagulation activation (fibrinopeptide A), granulocyte activation (lactoferrin), and platelet activation (beta-thromboglobulin). RESULTS: The concentrations of terminal complement complex, lactoferrin, and beta-thromboglobulin were significantly lower in association with heparin-coated surfaces. The concentration of plasma hemoglobin was significantly lower in association with the centrifugal pump. In uncoated circuits, the beta-thromboglobulin level was significantly higher in association with the roller pump than with the centrifugal pump, but this significant reduction in the beta-thromboglobulin level did not hold true for the heparin-coated circuit group. CONCLUSIONS: A heparin-coated cardiopulmonary bypass surface reduces the blood activation potential during cardiopulmonary bypass, and the centrifugal pump causes less hemolysis than the roller pump.
Adult↗
The excessive complement activation in fulminant meningococcal septicemia is predominantly caused by alternative pathway activation.
The relative contribution of the classical and alternative pathways in complement activation was quantified in 20 patients with systemic meningococcal disease. The activation products C4bc, C4bd, and Bb, indicating classical and alternative pathway activation, were measured with neoepitope-specific EIAs. Ten patients with persistent septic shock had significantly higher levels of Bb (P<.001), but not of C4bc (P=.43), than did 10 patients without septic shock. The Bb levels were significantly correlated with C3 activation products (C3bc; r= .72, P=.002), terminal SC5b-9 complement complex (TCC; r=.89, P<.001), and plasma lipopolysaccharides (LPS; r=.69, P= .01). There was no such association for C4bc versus C3bc, TCC, or LPS. Serially collected samples demonstrated activation of both pathways in patients with or without shock. Intervention strategies to stop the massive complement activation in fulminant meningococcal septicemia should include therapeutic principles that inhibit the alternative pathway.
Adult↗
Differences in blood activation related to roller/centrifugal pumps and heparin-coated/uncoated surfaces in a cardiopulmonary bypass model circuit.
An in vitro model cardiopulmonary bypass (CPB) circuit consisting ot tubing, oxygenator and venous reservoirs with either a roller or a centrifugal pump, and with either heparin-coated (Carmeda Bioactive Surface, CBAS) or uncoated surfaces, was studied with respect to 'blood activation', using small-scale-based blood volume (450 + 500 ml). Sixteen circuits were tested in each pump group, eight with and eight without heparin-coated surfaces, by circulating heparinized fresh human blood for 72 hours at 30 degrees C. Blood plasma, sampled at defined intervals, was analysed for haemolysis (lactate dehydrogenase and potassium), complement activation (C3bc and C5b-9 (TCC)), complement lytic inhibitors (vitronectin and clusterin), coagulation activation (fibrinopeptide A), granulocyte (lactoferrin and myeloperoxidase) and platelet (beta-thromboglobulin) activation and contaminating endotoxin. The heparin coating significantly reduced the concentrations of C3bc, TCC, fibrinopeptide A, lactoferrin, myeloperoxidase and beta-thromboglobulin. The two pump types did not differ with respect to these parameters, but the roller pump caused significantly higher increases in plasma LDH and potassium and significantly greater reductions in clusterin and vitronectin than the centrifugal pump. Endotoxin concentration was low at the start and after 24 hours in all groups. These results confirm that heparin-coated CPB surfaces reduce blood activation, and suggest that centrifugal pumps cause less haemolysis and less reduction in lytic complement inhibitors than roller pumps.
Blood Coagulation↗
Lipid composition of mononuclear cell membranes and serum from persons with high or low levels of serum HDL cholesterol.
High density lipoprotein (HDL) levels have been shown to be inversely correlated with the incidence of coronary artery disease (CAD). Since we have previously found that peripheral blood mononuclear cells (PBMC) from persons with high (n = 10) or low HDL (n = 10) have different functional properties, we wanted to examine the PBMC membrane lipid composition and fluidity, as well as to characterize the serum lipoproteins in greater detail. In persons with high HDL, PBMC membrane phospholipids were higher, and the cholesterol/phospholipid (CH/PL) ratio lower than in persons with low HDL. Membrane cholesterol and phospholipids were positively correlated with serum HDL2. The fatty acid composition of membrane phospholipids, and membrane fluidity was similar. The median saturated/unsaturated fatty acid (SFA/UFA) ratio tended to be lower in PBMC membranes and in serum from persons with high HDL; however this was not statistically significant. In serum, total phospholipids and HDL2 components (cholesterol, phospholipids and protein) were higher in persons with high HDL, whereas non-esterified fatty acids (NEFA) and very low density lipoprotein (VLDL) components (triglycerides, cholesterol, phospholipids and protein) were lower. Furthermore, serum cholesterol esters and the cholesterol esters/free cholesterol (CE/FC) ratio was higher, and the atherogenic index, i.e. (apoB X (total cholesterol-HDLc)/apoA-I X HDLc, lower in persons with high HDL. These results demonstrate that PBMC from persons with high or low serum HDL have a different lipid composition presumably of importance for cell function, lipid transport and atherogenesis.
Cell Membrane↗
Different binding of 125I-LPS to plasma proteins from persons with high or low HDL.
In severe trauma, sepsis or during surgery, bacterial lipopolysaccharide (LPS) frequently enters the circulation. Persons with high levels of high-density lipoprotein (HDL) have previously demonstrated higher monocyte procoagulant activity (PCA) when whole blood is challenged with LPS. The aim of the study was to investigate the distribution of radiolabelled LPS (125I-LPS) in plasma from six persons with high (2.14-2.82 mmol l-1) and six persons with low (0.54-1.04 nmol l-1) HDL, subjecting plasma to fast protein liquid chromatography (FPLC), or agarose electrophoresis followed by quantitative autoradiography. In heparin plasma 125I-LPS was located mainly in parts of plasma containing low-density lipoprotein (LDL) or very low-density lipoprotein (VLDL) and the immunoglobulins, and located to a lesser extent in HDL. However, persons with high HDL showed significantly higher binding of 125I-LPS to HDL and the immunoglobulins, probably to IgG, and significantly lower binding to LDL/VLDL. In calcium-depleted plasma (EDTA) 125I-LPS demonstrated a sharp increase in the binding to HDL, combined with a persistently high binding to LDL/VLDL and binding to the immunoglobulins was almost eliminated in all subjects investigated. Likewise, the binding of 125I-LPS to HDL in EDTA plasma was also significantly higher and to LDL/VLDL significantly lower in persons with high HDL. This study demonstrates that the distribution of 125I-LPS in heparin and EDTA plasma from persons with high or low HDL is different, which is presumed to be of importance concerning the various bioactivities of LPS.
Autoradiography↗
Collagen induced thrombus formation at the apex of eccentric stenoses--a time course study with non-anticoagulated human blood.
Atherosclerotic plaque rupture may trigger the formation of mural thrombus. This thrombus formation is apparently affected by very high and complex shear conditions introduced by the luminal narrowing (stenosis) of the atheroma. To study the impact of such blood flow behaviour on thrombus formation we employed a model system where collagen-induced thrombogenesis is studied at the apex of well-defined eccentric stenoses. Thrombus formation in non-anticoagulated human blood drawn directly from an antecubital vein over the collagen coated stenosis apex for periods of 0.5, 1, 3 or 5 min was quantified by morphometry. The stenoses reduced the cross-sectional area of the blood flow channel by 60, 80 and 89%, which corresponded to apex wall shear rates of 2600, 10,500 and 32,000 s-1, respectively. Platelet-collagen adhesion decreased by increasing shear at the stenosis apex. The corresponding adhesion rates were highest at 1 min, then they gradually decreased upon prolongation of the perfusion time. The platelet thrombus volume increased in concert with increasing shear rate up to 10,500 s-1, whereas, at 32,000 s-1, the volume wa decreased. The corresponding growth rates and rates of thrombus occlusion at the apex levelled off at 3 min. Significant fibrin deposition was not observed before 3 min, and was most pronounced at 10,500 and 32,000 s-1. The plasma levels of fibrinopeptide A and beta-thromboglobulin increased in concert with increasing shear and perfusion time, particularly at the two highest shear conditions. Thus, hallmarks of thrombus formation at these stenoses with increasing shear are decreased platelet-collagen adhesion, and increased platelet-platelet interaction and fibrin deposition. A fibrin tail downstream to the collagen-attached platelet thrombus is regularly observed when thrombus occlusion exceeds 40%. However, the reduced thrombus growth at the most occlusive stenosis (89%) is presumably due to the high shear stresses which may reduce the rate of platelet incorporation into the thrombus and/or tear off thrombus fragments.
Analysis of Variance↗
Acetylsalicylic acid and sodium salicylate inhibit LPS-induced NF-kappa B/c-Rel nuclear translocation, and synthesis of tissue factor (TF) and tumor necrosis factor alfa (TNF-alpha) in human monocytes.
We have investigated the effects of acetylsalicylic acid and sodium salicylate on the LPS-induced synthesis of the pro-coagulant protein tissue factor (TF) and the pro-inflammatory protein tumor necrosis factor-alpha (TNF-alpha), as well as the prostaglandin PGE2 in human monocytes. Both drugs dose-dependently inhibited LPS-induced TF and TNF-alpha synthesis at the mRNA and the protein level, and reduced PGE2 production. As evidenced by electro mobility shift assay (EMSA) and the use of a NF-kappa B prototypic probe, these drugs probably exert their inhibitory effects by interference with the nuclear translocation of NF-kappa B/c-Rel proteins. These data may expand the understanding of the anti-thrombotic and anti-inflammatory effects of these drugs when activation of monocytes occurs.
Anti-Inflammatory Agents, Non-Steroidal↗
Increased activation of coagulation and formation of late deep venous thrombosis following discontinuation of thromboprophylaxis after hip replacement surgery.
Hip replacement surgery (HRS) is associated with a high frequency of deep vein thrombosis (DVT). At the same time there is a substantial systemic and local activation of coagulation. This study indicates that discontinuation of thromboprophylaxis one week after surgery may allow a second wave of coagulation and fibrinolysis activation to occur. An almost parallel increase in plasma TAT and D-dimer levels between the 6th and the 35th postoperative day may indicate late DVT formation. Repeated bilateral ascending venography is though to be necessary to evaluate the suitability of using selected activation markers of the coagulation and fibrinolytic systems as indices of DVT formation.
Aged↗