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Biomedical subjects

J B Hansen

Publications and source records attributed to J B Hansen.

At least 91 records · Page 5Linked to original sources

Tissue-factor pathway inhibitor and lipoproteins. Evidence for association with and regulation by LDL in human plasma.

Tissue-factor pathway inhibitor (TFPI) is a potent inhibitor of extrinsic coagulation, which is mainly associated with lipoproteins in circulating blood. Gel filtration of human plasma confirmed the presence of three peaks in which approximately 10%, 70%, and 20% of total TFPI activity was retained. Precipitation of very-low-density lipoproteins and low-density lipoproteins (LDLs) in plasma by polyethylene glycol almost completely abolished peaks and I and II. LDL isolated by ultracentrifugation revealed two peaks of TFPI after gel filtration that coeluted with peaks I and II, respectively, from gel filtration of total plasma. TFPI activity in peaks I and II was also precipitated by anti-apolipoprotein B antibodies. Fourteen patients with familial hypercholesterolemia had higher plasma TFPI activity than did age- and sex-matched normolipemic control subjects (1.45 +/- 0.27 U/mL versus 0.80 +/- 0.09 U/mL, P < .001). Plasma TFPI was correlated with LDL cholesterol (r = .73, P < .001) and apolipoprotein B (r = .69, P < .001). No association was found with high-density lipoprotein cholesterol or apolipoprotein A-I. In a double-blind, placebo-controlled trial among the familial hypercholesterolemia patients, lovastatin alone or in combination with fish oil concentrate lowered plasma TFPI in parallel with LDL cholesterol. Gel filtration of plasma from these patients demonstrated a specific drop in apolipoprotein B-TFPI complexes, whereas TFPI not associated with lipoproteins was unchanged. This study demonstrated that plasma TFPI was associated with and regulated by LDL in plasma from healthy subjects and patients with familial hypercholesterolemia.

Adult↗

[Human Parvovirus B19 infection and aplastic crisis].

Human Parvovirus B19 (B19-virus) is the most frequent cause of aplastic crisis in patients with underlying hereditary haemolytic anaemia. B19-virus interrupts erythropoiesis by lytic damage of erythroid precursors in the bone marrow. Patients with hereditary haemolytic anaemia have a shortened red cell life span and a compensatory increased activity of the erythroid precursors in the bone marrow. Temporary interruption of erythropoiesis leads to a precipitous fall in haematocrit and absence of reticulocytes in the circulation. The symptoms of the illness are anaemia and fever. The treatment is red cell transfusion. The infection is diagnosed either by direct demonstration of B19-virus-DNA or by demonstration of specific IgM-antibodies to B19-virus. The natural infectivity of B19-virus is high, and infection is presumably followed by lasting immunity. Because the infectivity of cases of aplastic crisis caused by B19-virus is especially high, control guidelines are necessary for pregnant seronegative staff. A review of the literature is presented.

Anemia, Aplastic↗

[Occult hereditary spherocytosis in aplastic crisis of unknown cause].

We describe two cases of aplastic crisis of unknown origin, occurring within one week in a 49-year old man and his 20 year old son. They both had undiagnosed hereditary spherocytosis, and both of them had earlier had a B19-parvo infection without having symptoms of aplastic crisis at the same time. Chronic haemolytic anaemia should be considered in adult patients with acute severe anaemia caused by aplastic crisis.

Adult↗

Inhibition of exercise-induced shortening of bleeding time by fish oil in familial hypercholesterolemia (type IIa).

Fourteen patients suffering from familial hypercholesterolemia (type IIa) participated in a double-blind, placebo-controlled trial that evaluated the effects of fish oil ethyl ester (K-85, 5.7 g/day) or a hydroxymethylglutaryl coenzyme A reductase inhibitor (lovastatin, 40 mg/day) alone or in combination on lipid metabolism and bleeding time at rest and after standardized exercise. Lovastatin treatment reduced total cholesterol (-27%), low density lipoprotein cholesterol (-37%), and triglycerides (-18%), whereas high density lipoprotein cholesterol increased significantly (14%). K-85 affected total (-4%), low density lipoprotein (-9%), and high density lipoprotein (+7%) cholesterol insignificantly, whereas the triglyceride level decreased by 24% (p < 0.001). The combined regimen caused an additive decrease in the triglyceride level (41%), which differed significantly (p < 0.01) from that gained by lovastatin alone. Under basal conditions the bleeding time was not influenced by the different interventions. Standardized exercise shortened the bleeding time by 19% (p < 0.001) and 16% (p < 0.001) before intervention and after lovastatin treatment, respectively. After K-85 alone or in combination with lovastatin, the exercise-induced shortening of the bleeding time was totally inhibited, which may reflect a favorable influence of fish oil on the platelet-vessel wall interaction in these high-risk patients.

Adult↗

Comparative effects of prolonged intake of highly purified fish oils as ethyl ester or triglyceride on lipids, haemostasis and platelet function in normolipaemic men.

Conflicting results have been reported about the absorption of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) either as an ethyl ester (EE) or in a triglyceride (TG) formula. We decided to conduct a randomized double-blind study to compare the effects of EE and TG on plasma fatty acids, platelet function and haemostasis. Thirty-one healthy normolipaemic men were allocated to receive fish oil concentrate either as EE or TG with equal amounts of EPA (2.2 g and 2.2 g, respectively) and DHA (1.2 g and 1.4 g, respectively) or placebo daily for 7 weeks. Total cholesterol and the triglyceride level were not influenced differently by the two compounds. Repeated measurement ANOVA revealed a difference between TG and EE regarding incorporation of arachidonic acid (P = 0.034) and EPA (P = 0.007) into plasma cholesteryl esters. A discrimination not observed within plasma phospholipids. Both formulas had equal inhibitory effects on collagen-induced platelet aggregation and thromboxane B2 (TxB2) production in whole blood. Fibrinogen decreased 16% in EE (P = 0.034) and 12% in the placebo group (P = 0.11), but variance analysis of delta change during intervention did not indicate differences between groups. It is concluded that TG and EE fish oils are well incorporated into plasma lipids and have similarly beneficial influence one platelet function in men.

Adult↗

Effects of cod liver oil on lipids and platelets in males and females.

Thirty-four healthy non-smoking subjects (20 men and 14 women) were given 25 ml cod liver oil (CLO) daily as dietary supplement for 8 weeks in a controlled cross-over study. Prior to intervention, women had significantly higher serum total (P < 0.05) and high density lipoprotein (HDL) (P < 0.001) cholesterol values, higher platelet counts (P < 0.05) and lower thromboxane B2 (TxB2) generation (P < 0.01) in response to collagen stimulation in platelet-rich plasma (PRP) than men. Before intervention, no gender differences in platelet aggregation were observed. Following CLO intervention, serum triglycerides were reduced by 0.21 +/- 0.09 mmol/l (P < 0.05) in men. LDL cholesterol increased in men by 0.28 +/- 0.12 mmol/l (P < 0.05), while the values in women decreased insignificantly. The response in LDL cholesterol to CLO supplementation differed significantly between genders (P < 0.05). HDL cholesterol was not altered in any group. Mean platelet volume (MPV) increased by approximately 6% in both sexes (P < 0.01). After CLO intake, platelet sensitivity to collagen in PRP decreased in men only (P < 0.01), and the response was significantly different from that in women (P < 0.05). Thromboxane B2 generation following platelet aggregation in PRP was equally decreased by CLO. Our findings indicate sex differences in the response to CLO regarding LDL cholesterol and platelet sensitivity to collagen in PRP.

Adult↗

Inhibition of cisplatin-induced emesis in ferrets by the non-NMDA receptor antagonists NBQX and CNQX.

The excitatory amino acid (EAA) receptor antagonists, 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo(f)quinoxaline (NBQX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), which preferentially block non-N-methyl-D-aspartate (non-NMDA) subtypes of EAA receptors, effectively inhibit cisplatin-induced emesis in ferrets. A high dose of cisplatin (10 mg/kg i.v.) was used which induced emesis in all saline-treated control ferrets. At 10 mg/kg i.v., NBQX totally prevented cisplatin-induced emesis in 5 of 6 ferrets and CNQX totally prevented emesis in 3 of 5 ferrets. By comparison, each of the 5-HT3 inhibitors, zacopride and ondansetron, at 1.0 mg/kg i.v. (a dose considered in the high therapeutic range for controlling emesis by these compounds), totally prevented emesis in 2 of 5 ferrets. It is concluded that non-NMDA antagonists effectively inhibit cisplatin-induced emesis. They are potential antiemetic compounds, alone or in combination with 5-HT3 antagonists or other more conventional drugs of choice.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Streptococcus mutans serotype c tagatose 6-phosphate pathway gene cluster.

DNA cloned into Escherichia coli K-12 from a serotype c strain of Streptococcus mutans encodes three enzyme activities for galactose utilization via the tagatose 6-phosphate pathway: galactose 6-phosphate isomerase, tagatose 6-phosphate kinase, and tagatose-1,6-bisphosphate aldolase. The genes coding for the tagatose 6-phosphate pathway were located on a 3.28-kb HindIII DNA fragment. Analysis of the tagatose proteins expressed by recombinant plasmids in minicells was used to determine the sizes of the various gene products. Mutagenesis of these plasmids with transposon Tn5 was used to determine the order of the tagatose genes. Tagatose 6-phosphate isomerase appears to be composed of 14- and 19-kDa subunits. The sizes of the kinase and aldolase were found to be 34 and 36 kDa, respectively. These values correspond to those reported previously for the tagatose pathway enzymes in Staphylococcus aureus and Lactococcus lactis.

Aldehyde-Lyases↗

Rapid and specific cyclosporine assay for the Du Pont aca discrete clinical analyzer performed directly on whole blood.

A rapid, sensitive, and specific enzyme immunometric assay for cyclosporine in whole blood has been developed for the aca analyzer, using a monoclonal antibody from Sandoz, Ltd. Between-run CVs ranged from 6.5 to 7.6% for samples containing between 60 and 400 ng/mL cyclosporine. Sensitivity was better than 25 ng/mL in the assay, which has an effective upper range of greater than 600 ng/mL. Two correlation studies compared cyclosporine values from the Du Pont method to those determined by HPLC procedures in three hospital laboratories. The results from a total of 120 whole blood samples with CsA between 20 and 800 ng/mL showed excellent correlation between the methodologies. HPLC and Du Pont CsA values from 10 day serial studies also correlated well for samples from a kidney, kidney-pancreas, heart, and two liver transplant patients. We conclude that the Du Pont CSA assay provides accurate and reproducible results in a convenient format in less than 30 minutes.

Autoanalysis↗

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↗

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↗

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↗

Female sex hormones and platelet/endothelial cell interactions.

The effects of estradiol and progesterone added to the growth medium of human umbilical vein endothelial cells for 72 h on the formation and release of prostacyclin were investigated. The influence on collagen-induced platelet aggregation and on the platelet formation of thromboxane A2 following aggregation, of the growth medium collected before and after thrombin stimulation of the endothelial cells, was studied simultaneously. Under basal conditions, endothelial cells grown with progesterone released significantly less prostacyclin into the growth medium than did controls (p less than 0.05). Following thrombin stimulation, endothelial cells grown with estradiol (p less than 0.05) or a combination of estradiol and progesterone (p less than 0.01) contained significantly less prostacyclin than controls. No significant effects on the platelet aggregation or platelet thromboxane formation could be found. This study indicates a lowering effect of both female sex hormones on the endothelial cell prostacyclin formation and release. This may be of significance for the increased risk of vascular disease in pregnant women and oral contraceptive users, but can hardly explain the consequences of the hormonal loss occurring at the menopause.

6-Ketoprostaglandin F1 alpha↗

Anticonvulsant action of the beta-carboline abecarnil: studies in rodents and baboon, Papio papio.

Abecarnil (ZK 112119; isopropyl-6-benzyloxy-4-methoxymethyl-beta-carboxylate) is a metabolically stable beta-carboline derivative with potent anxiolytic and few sedative and ataxic effects in rodents. The anticonvulsant and muscle relaxant actions of abecarnil have been evaluated in mice, rats, gerbils and baboons. Abecarnil raised the threshold for tonic electroconvulsions in mice after corneal but not after auricular application, had no effect on maximal electroshock-induced tonic convulsions triggered by either method, protected mice against the tonic hindlimb extension in PTZ-, picrotoxin- and 3-mercaptopropionate-induced seizures and blocked clonus after PTZ, DMCM (methyl-4-ethyl-6,7-dimethoxy-9H-pyrido-(3,4-b)-indol-3-carboxylate) and 3-mercaptopropionate. Abecarnil had no effect on convulsions induced by bicuculline and strychnine. Furthermore, abecarnil blocked kindled seizures after chronic administration of PTZ and FG 7142 (beta-carboline-3-carboxylic acid methylamide) and protected mice and rats against limbic convulsions induced by pilocarpine. Severity and afterdischarge duration of amygdala-kindled seizures were reduced in rats treated with abecarnil. Abecarnil also antagonized selectively convulsions induced by i.c.v. administration of kainate, but not those triggered by N-methyl-D-aspartate or quisqualate. In genetic models of reflex epilepsy, abecarnil was effective against sound-induced convulsions in DBA/2 mice, against air blast-induced generalized seizures in gerbils and against myoclonus in baboons Papio papio. The anticonvulsant effect of abecornil in a PTZ seizure model in mice was potentiated by ethosuximide, whereas no significant potentiation was found with diazepam, clonazepam, diphenylhydantoin, carbamazepine and phenobarbital. Electromyographic monitoring in a etorphine model of muscle rigidity in rats showed no or little muscle relaxant effect of abecarnil.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Knowledge of AIDS and of transmission risks of HIV infection in a group of homosexual people. A questionnaire study].

A questionnaire investigation among 430 homosexual persons all of whom were members of an organization for homosexuals was completed by 144 (33%). These replies showed that they knew about HIV infection, risk behaviour and "safe sex". Their knowledge about the signs of HIV infection and AIDS was, however, more limited. The replies were compared with an age-matched group of the male population. The results of the investigation provide reasons to suppose that the information campaigns have been of value but information to prevent spread of infection is still necessary. In addition, further information is necessary about the subjective signs of HIV-infection so that persons in whom these signs develop may be offered the best possible treatment as early as possible.

Acquired Immunodeficiency Syndrome↗