| 1. |
- Nilsson, Peter, et al.
(författare)
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Effects of smoking cessation on insulin and cardiovascular risk factors--a controlled study of 4 months' duration
- 1996
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 240:4, s. 189-194
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate the effects on serum lipids, plasma fibrinogen, plasma insulin, plasma C-peptide and blood glucose, of smoking cessation after 4 months. To develop a group-based smoking intervention programme in primary health care. SETTING: Twenty health centres in primary health care in southern Sweden. SUBJECTS: Four hundred habitual smokers (> 10 cigarettes per day-1, > 10 years), recruited by advertisement in local papers. INTERVENTION: The smokers were randomized, after stratification for age and sex, to one intervention group (n = 200) and one control group (n = 200). The intervention group was offered supportive group sessions and free nicotine supplementation (patches, chewing gum). MAIN OUTCOME MEASURES: All participants were investigated at the start and after 4 months (medical history, physical examination, laboratory evaluation). Blood samples were drawn for determination of glucose, insulin and C-peptide, both in the fasting state and during an oral glucose tolerance test (OGTT), and for measurement of lipoproteins, fibrinogen, nicotine and cotinine. RESULTS: In the intervention group 98 of the subjects (48%) had quit smoking after 4 months. They were compared with the 156 subjects in the control group (91%) who were still daily smokers during the whole period. There were no significant differences in any variable between the two (total) experimental groups at baseline. Plasma nicotine and cotinine decreased (P < 0.001) in the intervention group following smoking cessation, and weight increased by 2.7 kg. In the intervention group HDL-cholesterol increased by 11% (P < 0.001), whereas HbA1c increased by 2% (P < 0.05) only in the control group. No changes occurred in levels of glucose, insulin, C-peptide and fibrinogen. CONCLUSION: The smoking cessation programme had a success rate of almost 50% over 4 months. Smoking cessation was associated with a marked increase in HDL-cholesterol levels but did not affect glucose tolerance. A concomitant weight increase may have blunted any independent beneficial effect of smoking cessation on glucose metabolism.
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| 2. |
- Ekström, Ulf, et al.
(författare)
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An individual with a healthy phenotype in spite of a pathogenic LDL receptor mutation (C240F)
- 1999
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Ingår i: Clinical Genetics. - : Wiley. - 0009-9163. ; 55:5, s. 332-339
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Tidskriftsartikel (refereegranskat)abstract
- Familial hypercholesterolemia (FH) is caused by a defect in the function of the low density lipoprotein (LDL) receptor and inherited in an autosomal, codominant way. In this study we present a 13-year-old girl, compound heterozygote for the LDL receptor mutations C240F and Y167X. Fibroblasts from the patient showed very low cholesterol esterification rate, LDL uptake, and degradation compared to normal fibroblasts (< 2%, 8%, and < 2%, respectively). The C240F mutant was expressed in LDL receptor deficient CHOMldlA7 cells. Analysis of cell extracts by immunoblotting demonstrated delayed processing of the mutated LDL receptor, which was accumulated as a precursor protein of normal size. A high molecular weight form of the receptor was also detectable in these cells, which probably reflects cross-linking through the unpaired cysteine residue in the binding domain. Cells expressing the C240F mutant protein were unable to mediate uptake and degradation of LDL. The two siblings of the index case also carried the C240F mutation, but surprisingly one of them (a 17-year-old brother) showed no signs of hypercholesterolemia. This observation is consistent with the view that there may be cholesterol lowering mechanisms that can be activated, perhaps by mutations in known or hitherto unknown genes.
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| 3. |
- Grimvall, E, et al.
(författare)
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Monitoring of polychlorinated biphenyls in human blood plasma: methodological developments and influence of age, lactation, and fish consumption
- 1997
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Ingår i: Archives of Environmental Contamination and Toxicology. - : Springer Science and Business Media LLC. - 0090-4341 .- 1432-0703. ; 32:3, s. 329-336
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Tidskriftsartikel (refereegranskat)abstract
- Human plasma samples from 50 wives of fishermen have been analyzed with respect to PCBs. The non-ortho-substituted PCB congeners CB-126 and CB-169 were determined by mass spectrometry in negative ion chemical ionization mode, which demonstrated a limit of detection of 30 fg. The recoveries of the internal standards used for determination of ortho-substituted CBs were approximately 95%. Two methods, one gravimetric and the other based on enzymatic determinations of triglycerides, cholesterol and phospholipids, were compared for the determination of total amount of lipids in the plasma samples; the correlation coefficient was 0.82 and the slope 0.98. For practical reasons, enzymatic determinations are recommended for further use. The total, lipid-adjusted concentrations of PCBs in plasma were influenced by age, total lactation time and consumption of fatty fish from the Baltic Sea.
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| 4. |
- Nilsson, A, et al.
(författare)
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Transient hypertriglyceridemia of infancy
- 1996
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Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 85:12, s. 1508-1510
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Tidskriftsartikel (refereegranskat)abstract
- A premature boy who had suffered from IRDS, bronchopulmonary dysplasia and retinopathy of prematurity developed massive hypertriglyceridemia (48.1 mmol/L) together with moderate hypercholesterolemia (12.6 mmol/L) at 5 months of age. Lipoprotein electrophoresis revealed a marked elevation of the level of the very low density lipoprotein fraction. There was a moderate decrease in the activity of a lipolytic enzyme, lipoprotein lipase (LPL). The child had neither liver or renal disorder nor any inflammatory disease. The hyperlipidemia disappeared spontaneously at the age of 3 years. The cause of the decreased LPL activity could not be established. A partial genetic deficiency in lipoprotein lipase appears the most likely explanation, since no signs of secondary lowering of LPL activity could be found.
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| 5. |
- Agardh, Carl-David, et al.
(författare)
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The effects of tolbutamide on lipoproteins, lipoprotein lipase and hormone-sensitive lipase
- 1999
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Ingår i: Diabetes Research and Clinical Practice. - 1872-8227. ; 46:2, s. 99-108
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetic patients are at increased risk to develop atherosclerotic vascular disease. These patients are often treated with sulphonylurea derivatives, and it has been suggested that this treatment might contribute to the increased atherosclerotic process. The aim of the present study was therefore to investigate whether tolbutamide influences lipid metabolism in such a way that the atherosclerotic process may be promoted. Addition of tolbutamide (5-500 mg/l) to isolated rat fat adipocytes inhibited the lipoprotein lipase (LPL) activity in a dose-dependent manner to levels about 50% of those registered in the absence of tolbutamide. This effect was due to inhibition of the activation of the enzyme in the tissue and not to interference with the interaction of enzyme with its substrate. Addition of tolbutamide (500 mg/l) also inhibited noradrenaline (100 nM) and isoprenaline (40 nM)-induced lipolysis by 48.1 +/- 7.4% (mean +/- S.E.M.) and 47.3 +/- 5.5%, respectively. The decreased lipolysis in tolbutamide preincubated adipocytes was shown to be the result of an inhibition of the phosphorylation of hormone sensitive lipase (HSL). Three months of tolbutamide treatment (0.5 g t.i.d.) in diet treated type 2 diabetic patients did not influence the plasma concentrations of cholesterol, triglycerides, LDL cholesterol, HDL cholesterol as well as HDL triglycerides and HDL phospholipids, and there were no differences compared to placebo treated patients. There was a tendency towards a decrement in the elimination rate of exogenous triglycerides in the tolbutamide group (P = 0.0801). No differences between the groups and no treatment effects were seen on LPL and hepatic lipase activities. In conclusion, our in vitro data show that tolbutamide has dual effects on lipid transport, with impairment of the LPL system, which would tend to decrease plasma lipoproteins by reducing hepatic production of lipoproteins. In vivo, these two effects seem to balance each other and plasma lipoprotein levels remain unaffected.
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| 6. |
- Arnadottir, Margret, et al.
(författare)
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Adrenocorticotrophic hormone lowers serum Lp(a) and LDL cholesterol concentrations in hemodialysis patients
- 1997
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Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 52:6, s. 1651-1655
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Tidskriftsartikel (refereegranskat)abstract
- Previously, we have shown that short-term administration of adrenocorticotrophic hormone (ACTH) results in reduced concentrations of apolipoprotein B-containing lipoproteins, including lipoprotein(a), and reduced activities of hepatic lipase. These effects were observed in steroid-treated patients suffering from iatrogenic ACTH deficiency and in healthy individuals. The direct nature of the influence of ACTH on hepatic lipoprotein metabolism was confirmed by in vitro experiments. The aim of the present investigation was to study the effects of ACTH treatment on uremic patients, who exhibit disturbed lipoprotein pattern due to the slow removal of triglyceride-rich lipoproteins and who probably are ACTH resistant. Eight patients on chronic hemodialysis were studied. After one intramuscular injection of Synacthen Depot (a synthetic ACTH1-24 preparation from Ciba Geigy AG, Basel, Switzerland) 1 mg, the only change noted was a significant reduction of 26% in median lipoprotein(a) concentration. After five injections, a further decrease (65%) was found in the lipoprotein(a) concentration. Also, reductions in median concentrations of total cholesterol, low density lipoprotein cholesterol and apolipoprotein B were observed. The magnitude of these changes was 15 to 30%. In contrast to previously studied groups, no changes were observed regarding triglyceride metabolism. Significantly increased median concentration of apolipoprotein CIII was found. However, the excess apolipoprotein CIII was confined to the fraction that was not associated with apolipoprotein B. Thus, administration of ACTH to uremic patients improved their atherogenic lipoprotein profile, a fact that may have future therapeutic implications. In comparison to previously studied groups, the uremic patients responded rather slowly and not at all regarding triglyceride metabolism.
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| 7. |
- Arnadottir, Margret, et al.
(författare)
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Corticotropin-induced reduction of plasma lipoprotein(a) concentrations in healthy individuals and hemodialysis patients: relation to apolipoprotein(a) size polymorphism
- 1999
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Ingår i: Metabolism, Clinical and Experimental. - 1532-8600. ; 48:3, s. 342-346
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Tidskriftsartikel (refereegranskat)abstract
- Lipoprotein(a) [Lp(a)], a strong independent cardiovascular risk factor, consists of the unique apolipoprotein(a) [apo(a)] covalently linked to a low-density lipoprotein particle. Apo(a) contains a widely differing number of the plasminogen-like kringle IV, a size polymorphism that is codominantly inherited. In addition to powerful genetic control, renal failure is known to influence the plasma Lp(a) concentration. There is still a lot to be learned about the mode and site of catabolism of Lp(a), and there is no readily applicable Lp(a)-lowering treatment available. Therefore, it was of interest to study further the Lp(a)-lowering effect of corticotropin (ACTH) that has been demonstrated in small studies. The main purpose of the present study was to investigate the influence of ACTH on different apo(a) isoforms. Short-term treatment with ACTH decreased the plasma Lp(a) concentration in all 26 study participants. The two study groups (12 healthy individuals and 14 hemodialysis patients) responded similarly, with a median decrease in plasma Lp(a) of 39% and 49%, respectively. In subjects with two clearly separable apo(a) bands, apo(a) phenotyping and densitometric scanning of the bands before and after treatment with ACTH revealed a change in the proportion of apo(a) isoforms, ie, a shift toward the isoform with lower molecular weight. This was observed in seven of nine investigated subjects (four of five healthy individuals and three of four hemodialysis patients).
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| 8. |
- Arnadottir, Margret, et al.
(författare)
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Hyperhomocysteinemia in cyclosporine-treated renal transplant recipients
- 1996
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Ingår i: Transplantation. - 1534-6080. ; 61:3, s. 509-512
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Tidskriftsartikel (refereegranskat)abstract
- Moderate hyperhomocysteinemia, an independent cardiovascular risk factor, has been reported in renal transplant recipients. In the present study, plasma concentrations of total homocysteine were significantly increased in 120 renal transplant recipients as compared with 60 healthy controls (19.0 +/- 6.9 vs. 11.6 +/- 2.8 mumol/L, P < 0.0001) and as compared with 53 patients without a transplant but with a comparable degree of renal failure (19.0 +/- 6.9 vs. 16.0 4.9 mumol/L, P < 0.01). There was a significant inverse correlation between glomerular filtration rates and plasma homocysteine concentrations in the renal transplant recipients (r = -0.52, P < 0.0001). Groups of renal transplant recipients, with and without cyclosporine, and renal patients without a transplant were studied; these groups were comparable regarding age, sex distribution, glomerular filtration rate, and folate and vitamin B12 concentrations. Renal transplant recipients on cyclosporine had significantly higher plasma homocysteine concentrations than those not on cyclosporine (19.5 +/- 7.6 vs. 16.2 +/- 4.8 mumol/L, P < 0.05), and the patients without a transplant (19.5 +/- 7.6 vs. 16.0 +/- 4.9 mumol/L, P < 0.01). Thus, the hyperhomocysteinemia of renal transplant recipients not treated with cyclosporine, and that of renal patients without a transplant probably is explained by the same mechanism: renal insufficiency. An additional mechanism seems to operate in renal transplant recipients treated with cyclosporine. The lack of correlation between the concentrations of plasma homocysteine and red cell folate in these patients suggests that cyclosporine interferes with folate-assisted remethylation of homocysteine. Plasma homocysteine concentrations were significantly increased in 24 patients with a history of atherosclerotic complications as compared with the remaining 96 renal transplant recipients (20.8 +/- 4.4 vs. 18.5 +/- 7.3 mumol/L, P < 0.01).
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| 9. |
- Arnadottir, M, et al.
(författare)
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The effect of reduced glomerular filtration rate on plasma total homocysteine concentration
- 1996
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 56:1, s. 41-46
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Tidskriftsartikel (refereegranskat)abstract
- The concentration of homocysteine in plasma has been shown to be increased in renal failure, possibly contributing to the accelerated atherosclerosis observed in uraemic patients. The aim of the present study was to document the relationship between plasma total homocysteine (tHcy) concentrations and glomerular filtration rates (GFR) in highly selected patients, with renal function ranging from normal to dialysis dependency. GFR was defined as the plasma clearance of iohexol; a more accurate method than the creatinine-based estimations applied in previous studies. Plasma tHcy concentrations were highly correlated to GFR (r = -0.70, p < 0.0001) and were significantly increased already in moderate renal failure. According to a multiple regression analysis, GFR and red cell folate concentrations independently predicted plasma tHcy concentrations, whereas those of serum creatinine, plasma pyridoxal-5-phosphate, urine albumin and urine alpha-1-microglobulin (a marker of tubular damage) did not. Thus, GFR seems to be a better determinant of plasma tHcy concentration than serum creatinine concentration. Plasma total cysteine and total cysteinylglycine concentrations followed the same pattern as those of tHcy.
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| 10. |
- Arnadottir, Margret, et al.
(författare)
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Very-low-density lipoprotein of uremic patients is a poor substrate for bovine lipoprotein lipase in vitro
- 1996
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Ingår i: Metabolism, Clinical and Experimental. - 1532-8600. ; 45:6, s. 686-690
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Tidskriftsartikel (refereegranskat)abstract
- Very-low-density lipoprotein (VLDL) from 10 hemodialysis patients and 10 healthy controls was studied with respect to the substrate characteristics for bovine milk lipoprotein lipase (LPL). Compared with the control subjects, the hemodialysis patients had significantly higher serum triglyceride and apolipoprotein B-associated apolipoprotein CIII concentrations (1.03 +/- 0.31 v 1.98 +/- 0.86 mmol/L and 0.004 +/- 0.002 v 0.011 +/- 0.005 g/L, respectively), lower serum high-density lipoprotein (HDL) cholesterol and apolipoprotein AI concentrations (1.33 +/- 0.37 v 0.95 +/- 0.31 mmol/L and 1.29 +/- 0.25 v 1.09 +/- 0.23 g/L, respectively), and lower postheparin plasma LPL activity (82 +/- 24 v 35 +/- 14 milliU/milliL). There were also significant increases in the relative fat content and diameter of VLDL particles from patients versus controls. VLDL was labeled with a fluorescent phospholipid analog, DHPE, and the rate of the lipolytic reaction with purified bovine milk LPL was estimated from the increase in fluorescence intensity at 490 nm. There was no significant difference between initial reaction velocities in the study groups, but VLDL particles from hemodialysis patients were lipolyzed to a significantly lesser extent than those from healthy controls (mean increase in fluorescence intensity after completion of the reaction, 95 +/- 36 v 140 +/- 43 arbitrary units). These results are in accordance with the accumulation of remnant particles reported to occur in uremia despite only a moderately increased serum triglyceride concentration.
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