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Biomedical subjects

J Dyerberg

Publications and source records attributed to J Dyerberg.

At least 55 records · Page 3Linked to original sources

Apolipoprotein(a) and cardiovascular disease in type 2 (non-insulin-dependent) diabetic patients with and without diabetic nephropathy.

The relative mortality from cardiovascular disease is on average increased five-fold in Type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy compared to non-diabetic subjects. We assessed the possible contribution of dyslipidaemia in general and elevated serum apolipoprotein(a) (apo(a)) in particular. Type 2 diabetic patients with normo-, micro- and macroalbuminuria were compared with healthy subjects. Each group consisted of 37 subjects matched for age, sex and diabetes duration. Serum creatinine in the nephropathy group was 105 (54-740) mumol/l. The prevalence of ischaemic heart disease (resting ECG, Minnesota, Rating Scale) was 57, 35, 19 and 2% in macro-, micro- and normoalbuminuric diabetic patients and healthy subjects, respectively. The prevalence of ischaemic heart disease was higher in all diabetic groups as compared to healthy subjects (p < 0.05), and higher in macroalbuminuric as compared to normoalbuminuric diabetic patients (p < 0.01). There was no significant difference between apo(a) in the four groups: 161 (10-1370), 191 (10-2080), 147 (10-942), 102 (10-1440) U/l (median (range)) in macro-, micro- and normoalbuminuric groups and healthy subjects. Serum total-cholesterol, HDL-cholesterol and LDL-cholesterol were not significantly different when comparing healthy subjects and each diabetic group. Apolipoprotein A-I was lower (p < 0.05) in all diabetic groups as compared to healthy subjects (nephropathy vs healthy subjects): 1.50 +/- 0.25 vs 1.69 +/- 0.32 g/l (mean +/- SD). Triglyceride was higher (p < 0.05) in patients with nephropathy and microalbuminuria as compared to healthy subjects (nephropathy vs healthy subjects): 2.01 (0.66-14.7) vs 1.09 (0.41-2.75) mmol/l (median (range)).(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗

The effect of low-dose supplementation with n-3 polyunsaturated fatty acids on some risk markers of coronary heart disease.

Epidemiological data have suggested that a low dose of dietary n-3 polyunsaturated fatty acids from seafood may protect against coronary heart disease. We studied the effect of supplementation with a low dose of very long-chain n-3 fatty acids (0.65 g day-1) on plasma lipids, haemostasis, and neutrophil aggregation. Twenty-four healthy subjects were randomized to supplementation with very long-chain n-3 fatty acids or a control oil for 8 weeks. Laboratory analyses were done twice before and twice at the end of the supplementation period. The supplement with n-3 polyunsaturated fatty acid did not significantly affect plasma lipids or plasma levels of fibrinogen, factor VII, plasminogen activator inhibitor, whole blood aggregation or aggregability of neutrophil leukocytes. Therefore, the potential beneficial effect of very long-chain n-3 fatty acids in coronary heart disease is likely to be mediated through other mechanisms.

Adult↗

No effect of human serum and erythrocytes enriched in n-3 fatty acids by oral intake on Plasmodium falciparum blood stage parasites in vitro.

To examine the effect of n-3 polyunsaturated fatty acids (n-3 PUFA) on the erythrocytic growth of Plasmodium falciparum, serum and erythrocytes were separated from blood of a healthy donor before and after he had taken fish oil capsules for 8 days. Such intake supplied an amount of eicosapentaenoic acid (EPA, 20:5n-3) of 3.5 g/d and docosahexaenoic acid (DHA, 22:6n-3) of 2.5 g/d and 24 mg/d of total tocopherol. Post-intake fish oil serum (post-s) and erythrocytes (post-e) were tested in vitro for inhibitory activity against blood stages of P. falciparum compared with pre-intake serum (pre-s) and pre-intake erythrocyte (pre-e). Also the effect of EPA and arachidonic acid (AA, 20:4n-6) on the erythrocytic growth of P. falciparum was tested using in vitro assays. The results show that both post-s and post-e had no antimalarial activity on P. falciparum. No differential antimalarial effect was observed for 20:5n-3 compared with 20:4n-6, which at high concentrations (> 40 microM) had an anti-schizont-growth effect.

Administration, Oral↗

The acute effect of a single very high dose of N-3 fatty acids on coagulation and fibrinolysis.

The objective of the study was to investigate the acute effect of a single very high dose of n-3 PUFA on coagulation and fibrinolysis. Forty healthy volunteers were randomized into two groups to receive either 20 grams of n-3 PUFA or 20 grams of n-6 PUFA as a single dose at 6 p.m. with their evening meal. Coagulation and fibrinolysis were evaluated in the fasting state at 8 a.m. the next morning and compared to values obtained at 8 a.m. the day before, when the participants were on their habitual diets. PAI-1 activity in plasma increased by a mean of 62% in subjects randomized to receive n-3 PUFA despite that no changes could be demonstrated in t-PA antigen levels. PAI-1 activity was unaltered in the 20 controls receiving n-6 PUFA. Plasma fibrinogen, coagulation factor VII, thrombin-antithrombin complexes and D-dimer did not significantly change after either supplement. The substantial increase in levels of PAI-1 activity in plasma after a single very high dose of n-3 PUFA may limit the usefulness of single very high doses of n-3 PUFA in acute clinical conditions.

Adult↗

Differences in apolipoprotein (a) polymorphism in west Greenland Eskimos and Caucasian Danes.

Previous studies in Greenland suggest that death rates from ischemic heart disease [IHD] are lower in Eskimos than in Danes and other Caucasian populations. This has been explained by a high intake of n-3 polyunsaturated fatty acids with beneficial effects on blood lipids and hemostasis. In other populations, lipoprotein(a) [Lp(a)] is associated with IHD, plasma concentrations of Lp(a) being genetically determined to a major extent. We have compared Lp(a) concentrations and apo(a) phenotypes in 120 Greenlandic Eskimos with those in 466 Danish men. The median Lp(a) concentration in Eskimos (8.7 mg/dl;[95% CI 6.5-10.7]) was not significantly different from that in Danes (6.3 mg/dl; [95% CI 5.2-7.0]), whereas the 90th percentile was significantly higher among Danes: 46.36 mg/dl; [95% CI 43.0-54.3] vs. 27.6 mg/dl [95% CI 20.7-36.9]. In 20% of the Danes, but in only 8% of the Eskimos (P = 0.009), the concentration of Lp(a) exceeded 30 mg/dl. The difference is probably explained by a low frequency of the low molecular weight apo(a) phenotypes among Eskimos, since the apo(a) isoforms F and B were absent, and the S1 and S2 types were present in only 3.3% of Eskimos. In contrast, these apo(a) isoforms were present in 26.6% of the Danes in either single-band or double-band phenotypes. The pattern of apo(a) polymorphism found in this study could provide part of a genetic explanation for the putative low rates of IHD in Eskimo populations.

Adult↗

Decreased interleukin-1 beta levels in plasma from rheumatoid arthritis patients after dietary supplementation with n-3 polyunsaturated fatty acids.

The effects of dietary supplementation with n-3 fatty acids on the level of cytokines and complement activation in plasma from patients with rheumatoid arthritis were examined. Thirty-two patients with active rheumatoid arthritis were included in a 12-week double-blind, randomized study of dietary supplementation with n-3 fatty acids (3.6 g per day) or placebo. The cytokines were measured in plasma before and after treatment with fish oil or placebo. In general, cytokine values at the upper limits of the calculated normal areas were found. The Interleukin-1 beta concentration in plasma was reduced significantly after 12 weeks of dietary supplementation with fish oil (p < 0.03). No significant difference was observed in the placebo group. The tumour necrosis factor alpha activity in plasma did not change significantly (p = 0.167). No significant changes were observed in the degree of complement activation. The clinical status of the patients was improved in the fish oil group, but not in the placebo group, judged by Ritchie's articular index (p < 0.02). We conclude that dietary supplementation with n-3 fatty acids results in significantly reduced plasma IL-1 beta levels in patients with rheumatoid arthritis. Even though the cytokine levels were low, the anti-inflammatory effect of n-3 fatty acids could in part be explained by their ability to decrease cytokine production.

Arthritis, Rheumatoid↗

Plasma lipoproteins and renal function during simvastatin treatment in diabetic nephropathy.

The aim of this study was to assess the effect of simvastatin on plasma lipoproteins and renal function in hypercholesterolaemic Type 1 (insulin-dependent) diabetic patients with diabetic nephropathy. Twenty-six hypercholesterolaemic (total cholesterol greater than or equal to 5.5 mmol/l) Type 1 diabetic patients with nephropathy were enrolled in a double-blind randomized placebo-controlled study for 12 weeks. The active treatment group (n = 14) received simvastatin (10-20 mg/day) for 12 weeks while the remaining 12 patients received treatment with placebo. The results during simvastatin treatment (baseline vs 12 weeks): total cholesterol 6.6 vs 4.8 mmol/l (p less than 0.01), LDL-cholesterol 4.25 vs 2.57 mmol/l (p less than 0.01) and apolipoprotein B 1.37 vs 1.06 mmol/l (p less than 0.01). HDL-cholesterol, and apolipoprotein A-I remained unchanged. Total cholesterol, LDL-cholesterol, HDL-cholesterol, apolipoprotein A-I, apolipoprotein B remained unchanged during placebo treatment. Albuminuria measured during the simvastatin and the placebo treatment (baseline vs 12 weeks) (the data are logarithmically transformed before analysis because of their positively skewed transformation; geometric mean (x/divided by antilog SE) is indicated) was 458 (x/divided by 1.58) vs 393 (x/divided by 1.61) and 481 (x/divided by 1.62) vs 368 (x/divided by 1.78 micrograms/min (NS). Glomerular filtration rate during simvastatin and placebo treatment (baseline vs 12 weeks) was 64 vs 63 and 72 vs 74 ml.min-1.1.73 m-2, respectively. Two patients receiving simvastatin treatment were withdrawn, one due to gastrointestinal side effects and one due to myalgia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effects of dietary supplementation with n-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized, double blind trial.

STUDY OBJECTIVE: To determine the effect of dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) on disease variables in patients with rheumatoid arthritis. DESIGN: Multicenter, randomized, placebo controlled, double blind. SETTING: Three Danish hospital Departments of Rheumatology. PATIENTS: Fifty-one patients with active rheumatoid arthritis. INTERVENTION: Random allocation to 12 weeks of treatment with either six n-3 PUFA capsules (3.6 g) or six capsules with fat composition as the average Danish diet. MAIN RESULTS: Significant improvement of morning stiffness and joint tenderness. No significant effect on the four other assessed clinical parameters. No serious side effects. CONCLUSIONS: Dietary supplementation with n-3 PUFA in patients with rheumatoid arthritis improved two out of six patient reported disease parameters. Further studies are needed to clarify the more precise role of n-3 PUFA in the treatment of rheumatoid arthritis.

Adult↗

n-3 polyunsaturated fatty acid supplementation (Pikasol) in men with moderate and severe hypertriglyceridaemia: a dose-response study.

The effect of n-3 fatty acids in 11 men with hypertriglyceridaemia was investigated. The subjects were given daily supplements with three different doses of n-3 fatty acids for 8-week periods. The supplements given were 2, 4 and 9 g of n-3 fatty acids/day, respectively. Total cholesterol, triglycerides and the ratio of total cholesterol to HDL-cholesterol significantly decreased with all three doses in a dose-dependent way. HDL-cholesterol increased in a dose-dependent fashion, while apolipoproteins A1 and B were unaltered by the supplements apart from a small increase in apolipoprotein A1 after the lowest dose of n-3 fatty acids. The greatest effect was observed after 2 g of n-3 fatty acids/day.

Adult↗

Long-term supplementation with n-3 fatty acids, I: Effect on blood lipids, haemostasis and blood pressure.

The effect of dietary supplementation with 4 g of n-3 polyunsaturated fatty acids (PUFA) daily for 9 months on blood pressure, plasma lipids and lipoproteins, platelet function, coagulation and fibrinolysis was studied in 24 healthy volunteers. Each variable was determined before, after 6 weeks and 9 months of supplementation with n-3 PUFA, and 3 months after the supplementation period had ended. Systolic and diastolic blood pressure declined after intake of n-3 PUFAs. Plasma triglycerides were reduced, and there was a trend towards an increase in HDL-cholesterol after 9 months of supplementation, while total cholesterol, LDL-cholesterol and apolipoproteins A1 and B were unaltered. The bleeding time was increased, and plasma levels of von Willebrand factor decreased after 9 months supplementation with n-3 PUFA. Fibrinogen levels increased, while fibrinolysis was reduced after 9 months supplementation with n-3 PUFA. Overall, no clear benefit on lipid pattern and haemostasis was achieved with respect to development of coronary heart disease.

Adult↗

Long-term supplementation with n-3 fatty acids, II: Effect on neutrophil and monocyte chemotaxis.

The effect of a daily supplement with 4 g of n-3 polyunsaturated fatty acids (PUFA) for 9 months to 24 healthy volunteers on neutrophil and monocyte chemotaxis was studied using the under-agarose technique. Autologous serum and n-formyl-methionyl-leucyl-phenylalanine were used as chemoattractants. The effect after 9 months of supplementation with n-3 PUFA was also compared to results after short-term supplementation with n-3 PUFA for 6 weeks. Monocyte chemotaxis was reduced after 9 months of supplementation with n-3 PUFA to the same extent as after 6 weeks supplement. Neutrophil-directed migration towards chemoattractants was reduced after 9 months on fish oil, and this decrease was significantly greater than the decrease obtained after 6 weeks of supplementation. The spontaneous migration of neutrophils was significantly attenuated after 9 months compared to baseline and to 6 weeks. These findings lend support to a role for n-3 PUFA in the management of chronic inflammatory and atherosclerotic vascular diseases.

Adult↗

Apolipoprotein(a) in insulin-dependent diabetic patients with and without diabetic nephropathy.

Insulin-dependent diabetic patients with diabetic nephropathy have a highly increased morbidity and mortality from cardiovascular diseases. To determine whether altered levels of apolipoprotein(a) (apo(a)), the glycoprotein of the potentially atherogenic lipoprotein(a) (Lp(a)), contribute to the increased risk of ischaemic heart disease, apo(a) was determined in 50 insulin-dependent diabetic patients with diabetic nephropathy (group 1), in 50 insulin-dependent diabetic patients with microalbuminuria (group 2), in 50 insulin-dependent diabetic patients with normoalbuminuria (group 3), and in 50 healthy subjects (group 4). The groups were matched with regard to sex, age and body mass index. The diabetic groups were also matched with regard to diabetes duration. The level of apo(a) was approximately the same in the four groups, being: 122 (x/ divided by 4.2) U l-1, 63 (x/ divided by 4.4) U l-1, 128 (x/ divided by 3.5) U l-1 and 126 (x/ divided by 3.7) U l-1 (geometric mean (x/ divided by antilog SD)) in group 1, 2, 3 and 4, respectively. 1 U l-1 apo(a) approximates 0.7 mg l-1 Lp(a).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Standardized prothrombin time determinations and optimal anticoagulant therapy].

WHO and other international organizations have recommended the introduction of a standardized prothrombin time determination. This would allow a universal scale for the intensity of oral anticoagulation therapy to be used. A prerequisite is the use of thromboplastin, calibrated against the international reference thromboplastin, standardized methodology etc. This permits every prothrombin time determination to be expressed as International Normalized Ratio (INR). The introduction of INR facilitates the implementation of optimal oral anticoagulation as defined by larged international studies.

Anticoagulants↗

Dietary supplementation with omega-3-polyunsaturated fatty acids decreases mononuclear cell proliferation and interleukin-1 beta content but not monokine secretion in healthy and insulin-dependent diabetic individuals.

The effects of dietary supplementation with omega-3-polyunsaturated fatty acids (omega-3-PUFA) on the proliferative response of PBMC and on the secretion of monokines and arachidonic acid metabolites from PBMC and monocytes (Mo) from healthy subjects and patients with recent-onset insulin-dependent diabetes mellitus (IDDM) were examined. Three groups of eight to nine healthy individuals were randomized to either 2.0 g/day or 4.0 g/day of omega-3-PUFA devoid of vitamins A and D, or an isocaloric amount of placebo. Furthermore, eight patients with recent-onset IDDM received 4.0 g/day of omega-3-PUFA. IL-1 beta production and TNF-alpha secretion was determined before and after 7 weeks of treatment, and 10 weeks after withdrawal of treatment. Significant increases in platelet and PBMC membrane eicosapentaenoic acid was found in omega-3-PUFA-treated individuals. omega-3-PUFA treatment significantly reduced the content of IL-1 beta in lysates of PBMC, but did not affect PBMC or Mo secretion of IL-1 beta, TNF-alpha or prostaglandin E2 (PGE2) or PBMC leukotriene B4 (LTB4) secretion in healthy subjects or in IDDM patients. A significant inhibition of the PHA-stimulated, but not the spontaneous or PPD-stimulated, proliferative response of PBMC was observed in healthy and diabetic subjects treated with omega-3-PUFA. No correlation was found between PHA-stimulated PBMC proliferation and PBMC secretion of TNF-alpha and IL-1 beta. There were no significant differences in the spontaneous or the PPD- or PHA-stimulated proliferative responses of PBMC between diabetic and healthy individuals at entry. We conclude that although dietary supplementation with 4.0 g/day of omega-3-PUFA inhibits the proliferation of PBMC and reduces IL-1 beta immunoreactivity in PBMC and Mo, it does not alter monokine, PGE2 or LTB4, secretion in healthy or IDDM subjects.

Adult↗