| 1. |
- Nilsson, Peter, et al.
(author)
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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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In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 240:4, s. 189-194
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Journal article (peer-reviewed)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.
(author)
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An individual with a healthy phenotype in spite of a pathogenic LDL receptor mutation (C240F)
- 1999
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In: Clinical Genetics. - : Wiley. - 0009-9163. ; 55:5, s. 332-339
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Journal article (peer-reviewed)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. |
- Fagher, B, et al.
(author)
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L-carnitine and haemodialysis: double blind study on muscle function and metabolism and peripheral nerve function
- 1985
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - 1502-7686. ; 45:2, s. 169-178
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Journal article (peer-reviewed)abstract
- Twenty-eight haemodialysis patients were randomized to L-carnitine, 2 g i.v. three times a week, and saline over a 6-week period. No obvious deficiency of carnitine was found in vastus lateralis with a median value of 12.9 mmol/kg dry weight; range 6.2-21.4. Female patients had lower total plasma carnitine compared to female controls, p less than 0.002, whereas no decrease was found in males. No relationship was found between muscle and total plasma carnitine. After carnitine administration the muscle carnitine level increased about 60%, p less than 0.01, and the total plasma carnitine level more than tenfold, whereas the initially high degree of acylation decreased, p less than 0.02. Maximum dynamic muscular strength was reduced with a mean value of 44% compared with healthy controls. Total metabolic activity of isolated skeletal muscle fibres, measured as heat production with a new technique using a perfusion microcalorimeter, showed a median value of 0.40 mW/g, 25% lower than normal, p less than 0.02. Carnitine administration had no effect on several different tests of muscular function. Neurophysiologically, discrete improvements in the temperature responses were recorded, but no changes in sensory and motor nerve conduction velocities or in vibration thresholds were noted. No symptomatic improvement was observed even in patients with the lowest carnitine levels prior to treatment. Our data do not support the hypothesis that carnitine deficiency contributes to muscle and nerve dysfunction in patients on chronic haemodialysis.
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| 4. |
- Hansson, P, et al.
(author)
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Hepatic lipase activity increases after liver denervation in the rat
- 1985
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In: Biochimica et Biophysica Acta. - 0006-3002. ; 833:2, s. 351-353
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Journal article (peer-reviewed)abstract
- We have investigated the effects of hilar denervation of rat liver upon the activity of hepatic lipase determined in tissue extracts. Denervated animals had an enzyme activity of 7.89 +/- 0.37 mU/mg protein, compared to 6.45 +/- 0.43 in sham-operated controls (mean +/- S.E.; P less than 0.05). We conclude that hepatic innervation may contribute to the regulation of hepatic lipase activity.
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| 5. |
- Arnadottir, M, et al.
(author)
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The effect of reduced glomerular filtration rate on plasma total homocysteine concentration
- 1996
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 56:1, s. 41-46
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Journal article (peer-reviewed)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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| 6. |
- Berg, Anna-Lena, et al.
(author)
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Beneficial effects of ACTH on the serum lipoprotein profile and glomerular function in patients with membranous nephropathy
- 1999
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In: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 56:4, s. 1534-1543
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Journal article (peer-reviewed)abstract
- BACKGROUND: Previous studies have shown that short-term treatment with adrenocorticotrophic hormone (ACTH) has a strong and rapid lipid-lowering effect. In this long-term study of nephrotic patients with idiopathic membranous nephropathy, the influence of ACTH on the serum lipoprotein profile and glomerular function as well as the dose-effect relationship was investigated. METHODS: Fourteen patients received ACTH intramuscularly at increasing doses during 56 days. Serum concentrations of lipids, lipoproteins, and apolipoproteins as well as variables of glomerular function were analyzed, and the side-effects were recorded. ACTH treatment, in the estimated optimal dosage, was then continued in five patients with severe steroid-resistant nephrotic syndrome. In these five patients, the total treatment period was 12 months, and the follow-up time after discontinuing treatment was 18 months. RESULTS: Taking both the statistically significant therapeutic effects and the modest side-effects into consideration, the optimal dosage of ACTH was estimated to be 1 mg twice per week. At that dose, reductions by 30 to 60% in the serum concentrations of cholesterol, triglycerides, apolipoprotein B, and lipoprotein(a) were observed, whereas the serum concentrations of high-density lipoprotein cholesterol and apolipoprotein AI rose by 30 to 40%. In addition, the urinary albumin excretion decreased by 90%, and the glomerular filtration rate increased by 25%. Deterioration was observed in all cases when ACTH was discontinued after a treatment duration of 56 days. However, the five patients in whom ACTH therapy was resumed were still in remission 18 months after discontinuance of treatment. CONCLUSIONS: In nephrotic patients with idiopathic membranous nephropathy, treatment with ACTH 1 mg twice per week was associated with significant long-term improvements in serum lipoprotein pattern and glomerular function.
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| 7. |
- Bitzén, Ulrika, et al.
(author)
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Retinyl palmitate is a reproducible marker for chylomicron elimination from blood
- 1994
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 54:8, s. 611-613
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Journal article (peer-reviewed)abstract
- To study the individual variation in chylomicron clearance rate, young healthy volunteers were given a p.o. dose of 50,000 IU retinyl palmitate in the morning to label their chylomicrons. Serial blood samples were then obtained in the time interval 4-8 h after retinyl palmitate intake, to closely monitor the clearance of retinyl ester from the blood. The procedure was repeated in an identical way two days later. The calculated individual halflives for retinyl palmitate clearance ranged from 1.54 to 9.90 h, i.e. a more than five-fold variation. The intraindividual variation was much less (relative SD 11%). Retinyl palmitate clearance (and probably chylomicron clearance) is, thus, relatively constant within the same individual on different occasions but varies considerably between individuals.
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| 8. |
- Ekström, Ulf, et al.
(author)
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Expression of an LDL receptor allele with two different mutations (E256K and I402T)
- 2000
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In: Molecular Pathology. - 1366-8714. ; 53:1, s. 31-36
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Journal article (peer-reviewed)abstract
- AIMS: To investigate the disease causing event in patients with familial hypercholesterolaemia, carrying two mutations each, E256K in exon 6 and I402T in exon 9, of the gene encoding the low density lipoprotein (LDL) receptor. It was not known whether the mutations were positioned in cis or trans, or if they were each pathogenic separately or only when present together. METHODS: Polymerase chain reaction, denaturing gradient gel electrophoresis and sequencing were used to characterise the LDL receptor locus of the patients and family members. The different LDL receptor mutants, constructed in vitro by oligonucleotide directed mutagenesis, were expressed in LDL receptor deficient Chinese hamster ovary (CHO1d1A7) cells, to determine the effects of the mutations on LDL receptor function. RESULTS: The two mutations were located on the same allele of the LDL receptor gene. All mutant constructs resulted in the production of a detectable protein in CHO cells. The cells expressing only the I402T mutation, or the combination of I402T and E256K mutations, were seriously affected in mediating uptake and degradation of LDL. Contrary to initial predictions, the cells expressing only the E256K mutation showed essentially the same binding, uptake, and degradation of 125I labelled LDL as cells transfected with normal LDL receptor cDNA. These results suggest that the pathogenic mutation in the patients heterozygous for the E256K/I402T allele is the I402T mutation, and that E256K alone is a rare sequence variation, which does not affect LDL receptor protein function. E256K was not detected either in DNA from a healthy population or in DNA from other hypercholesterolaemic patients studied. CONCLUSIONS: Despite the information available on the structure-function relations between the LDL receptor and LDL receptor like proteins, predictions about the disease causing potential of a mutation are not reliable. These results suggest that the I402T mutation is pathogenic and that the substitution of E256K alone is a rare sequence variation, without a detectable phenotype modulating effect.
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| 9. |
- Garfinkel, A G, et al.
(author)
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Regulation of lipoprotein lipase. Induction by insulin
- 1976
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In: Biochimica et Biophysica Acta. - 0006-3002. ; 424:2, s. 264-273
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Journal article (peer-reviewed)abstract
- Lipoprotein lipase activity in intact epididymal adipose tissue of fasted rats increased rapidly after treatment with insulin in vivo. In contrast, lipoprotein lipase activity in adipocytes isolated from the contralateral fat pads remained essentially unchanged. When adipocytes were incubated for 30 min at ambient temperature in vitro, about 2 times more lipoprotein lipase activity was found in the medium of cells from insulin-treated rats than in medium from cells of control animals. Following insulin treatment, extracts of tissue acetone powders separated by gel chromatography showed increases in both enzyme activity fractions obtained (designated lipoprotein lipase a and b). However, no consistent differences were observed between fractions derived from adipocyte acetone powders of insulin-treated and control animals. All the observed effects of insulin on lipoprotein lipase activity were abolished by cycloheximide treatment in vivo. These data indicate that following insulin treatment, increased lipoprotein lipase activity in adipose tissue results from enhanced enzyme secretion by the fat cell and subsequent accumulation in the tissue, thus implicating the adipocyte secretory mechanism as a major site of regulation of lipoprotein lipase activity in adipose tissue.
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| 10. |
- Henriksson, K M, et al.
(author)
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Development of hypertension over 6 years in a birth cohort of young middle-aged men: the Cardiovascular Risk Factor Study in southern Sweden (CRISS).
- 2002
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In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 252:1, s. 21-26
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To explore the development of hypertension (HT) in a cohort of young middle-aged men. DESIGN: Prospective birth-cohort study of men surveyed over 6 years. SETTING: Helsingborg County Hospital, Sweden, 1990-97. SUBJECTS: A total of 628 men born in 1953-54, all surveyed at 37, 40 and 43 years of age. MAIN OUTCOME MEASURES: Systolic blood pressure (SBP), diastolic blood pressure (DBP), S-cholesterol, body mass index (BMI), alcohol consumption, ethnicity. HT was defined as SBP > or = 140 mmHg and/or DBP > or = 90 mmHg, or ongoing treatment. Using SBP < 130 mmHg and DBP < 85 mmHg as reference, the odds of conversion to HT in men with high normal blood pressure (BP) (SBP 130-139 mmHg and DBP 85-89 mmHg) was investigated. RESULTS: At age 37, 243 men (39%) had reference BP, 167 (26%) had high normal BP and 218 (35%) were hypertensive. Corresponding numbers at age 40 were 265 (42%), 166 (27%) and 197 (31%); and at age 43, 180 (29%), 142 (22%) and 306 (49%), respectively. High normal BP at baseline was associated with the development of HT both at age 40 (odds ratio (OR)=2.45 confidence interval (CI): 1.42-4.22) and at age 43 (OR=2.46, CI: 1.59-3.80), independent of other cardiovascular disease risk factors and ethnicity. The progression to HT was predicted also by S-cholesterol, alcohol consumption, BMI and weight gain. CONCLUSIONS: Over a short-term period, a substantial proportion of young middle-aged men with high normal BP develop HT with overweight and alcohol consumption as important determinants. These findings have implications for the prevention, screening and medical care of HT in this target population.
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