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Biomedical subjects

H Gylling

Publications and source records attributed to H Gylling.

At least 109 records · Page 6Linked to original sources
PubMed1992

Cholesterol absorption and synthesis related to low density lipoprotein metabolism during varying cholesterol intake in men with different apoE phenotypes.

The aim of the present study was, first, to investigate whether cholesterol (C) absorption, enhanced by cholesterol feeding, was related to synthesis of cholesterol, serum level of low density lipoprotein (LDL)-C, and receptor activity for LDL apolipoprotein (apo) B in healthy men. Secondly, we were interested in whether apolipoprotein E (apoE) phenotypes contributed to cholesterol and LDL apoB metabolism under these conditions. We studied 29 home-living men aged 55 +/- 1 (mean +/- SE) years on a low-fat, low cholesterol (208 +/- 13 mg/day) diet followed by a low-fat high cholesterol (878 +/- 38 mg/day) diet during 5 weeks. Cholesterol feeding increased total cholesterol, LDL-C, high density lipoprotein (HDL)-C, and LDL apoB levels from 10% to 13% (P less than 0.05) and bile acid production and cholesterol turnover by 16% (P less than 0.05), decreased the fractional catabolic rate (FCR) for LDL apoB by 10% (P less than 0.05) and cholesterol absorption efficiency by 8% (P less than 0.05), while cholesterol synthesis only tended to decrease. During the cholesterol feeding, LDL-C was positively related to apoB production rate and cholesterol absorption efficiency (P less than 0.05), and negatively related to bile acid and cholesterol synthesis (P less than 0.05) and FCR for LDL apoB, which, in turn, was negatively related to cholesterol absorption efficiency and positively to bile acid synthesis. ApoE phenotype was positively related to TC, LDL-C, and LDL apoB levels and negatively to FCR for LDL apoB. The increase of the LDL-C level by the high cholesterol intake was positively correlated with LDL-C on high cholesterol diet and apoE phenotypes, so that the increase was 7% in apoE2 (ns), 11% in apoE3 (P less than 0.05), and 18% in apoE4 (P less than 0.05); the increase of bile acid synthesis was significant only in subjects with apoE2. Moreover, the increase of LDL-C was positively related to the absolute amount of dietary cholesterol absorbed and negatively to FCR for LDL apoB. The findings suggest that the higher the LDL-C level, the higher is the absorption efficiency of cholesterol and production of LDL apoB, and the lower is the removal of LDL apoB and synthesis of both bile acids and cholesterol, and the more frequently the subjects had epsilon 4 allele. The nonresponsiveness to dietary cholesterol was dependent on low LDL-C level, apoE2 phenotype, and effective bile acid synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗
PubMed1992

Physiologic mechanisms for reduced apolipoprotein A-I concentrations associated with low levels of high density lipoprotein cholesterol in patients with normal plasma lipids.

Low plasma concentrations of high density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apoA-I) are major risk factors for coronary heart disease (CHD). Low HDL levels are common in patients with hypertriglyceridemia, but they also occur in those with normal plasma lipids; the latter include obese patients and cigarette smokers, though other patients with low HDL levels are neither obese nor smokers. The present study was designed to define metabolic causes of low apoA-I levels in normal-weight, normolipidemic patients. ApoA-I tracer studies were carried out in two groups of normolipidemic patients having low HDL levels to determine input rates and residence times for ApoA-I; these patients included 11 nonobese nonsmokers and 11 nonobese cigarette smokers. Their results were compared to those of 20 normal-weight, normolipidemic controls with normal HDL levels and 12 obese nonsmokers also having low HDL. In all three groups manifesting low HDL-cholesterol and low apoA-I levels, residence times for plasma apoA-I were reduced by approximately 30%, compared to control subjects with normal HDL levels. In contrast, average input rates for apoA-I were similar among the three low-HDL patients and control subjects. No differences in apoA-I kinetics were observed among any of the three groups with low apoA-I concentrations. Within each of the four groups of the study, however, input rates for apoA-I were highly correlated with plasma concentrations of apoA-I. Thus, for individuals with normal levels of plasma lipids, both residence times and input rates for apoA-I appeared to be important determinants of apoA-I levels. Residence times for apoA-I were reduced in almost all patients with low apoA-I levels, regardless of concomitant factors, whereas input rates were highly variable among individuals.

Aged↗
PubMed1991

Hypolipidemic effect and mechanism of ketoconazole without and with cholestyramine in familial hypercholesterolemia.

The hypocholesterolemic and metabolic effects of ketoconazole (400 mg/d) alone (inhibits cholesterol synthesis at 14 alpha-demethylation of lanosterol) and in combination with cholestyramine (12 g/d), were studied in nine women with xanthomatous familial hypercholesterolemia (FH). In addition to serum lipoprotein levels, cholesterol precursors, fecal steroids, and cholesterol absorption were measured before and during the drug treatments. Serum total and low-density lipoprotein (LDL)-cholesterol were reduced by 19% and 22% with ketoconazole; the respective changes were 16% and 21% for cholestyramine, and 31% and 41% for the combined ketoconazole and cholestyramine treatment. Serum triglycerides, very-low-density lipoprotein (VLDL)-and high-density lipoprotein (HDL)-cholesterol levels were unchanged. Accumulation of cholesterol precursors in serum suggested that ketoconazole inhibited cholesterol synthesis at delta 8-sterol levels. Serum and fecal lanosterols were increased up to 20-fold and were interrelated. Their maximal serum level was 1.3 mg/DL and the lanosterol contents were negatively related to the serum cholesterol levels. The intestinal absorption and total intestinal fluxes of cholesterol were reduced by 27% and 29%. Cholesterol and bile acid synthesis were decreased by ketoconazole only when combined with cholestyramine. The synthesis of chenodeoxycholic acid was deeply hindered by ketoconazole. Thus, ketoconazole efficiently lowers serum total and LDL-cholesterol levels in FH patients, probably by inhibiting cholesterol synthesis and absorption. Effective biliary and fecal outputs of cholesterol precursors prevent their excessive increase in serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Evaluation of a method for study of kinetics of autologous apolipoprotein A-I.

Apolipoprotein A-I (apoA-I) participates in transport of plasma cholesterol. Concentrations of apoA-I depend on the balance between production and fractional clearance. To elucidate factors influencing apoA-I levels, accurate estimates of apoA-I turnover rates may be valuable. We describe a method for isolation of autologous apoA-I and its use in turnover studies. Free apoA-I was isolated from high density lipoproteins (HDL) by treatment with guanidine hydrochloride. This free apoA-I was radioiodinated with 131I and injected into eleven subjects simultaneously with HDL labeled with 125I. Plasma die-away curves of free apoA-I (131I) and HDL apoA-I (125I) were compared; fractional clearance rates averaged 0.256 +/- 0.019 (SEM) and 0.254 +/- 0.017 pools/day, respectively. Although slight differences between the two die-away curves were noted for some of the patients, the differences were relatively small; for the group as a whole, average fractional catabolic rates were not significantly different. Thus, by isolation of autologous apoA-I under the conditions described, free apoA-I seemingly provides a valid method for estimating apoA-I turnover.

Adult↗
PubMed1990

Phagocyte function in familial hypercholesterolaemia: peripheral blood monocytes exposed to lipopolysaccharide show increased tumour necrosis factor production.

We studied functions of polymorphonuclear leucocytes (PMN) and monocytes from peripheral blood of subjects with familial hypercholesterolaemia (FH). FH monocytes exposed to Escherichia coli lipopolysaccharide (LPS) in 10% human AB serum generated tumour necrosis factor (TNF) significantly more than did control monocytes. After lowering of serum low-density lipoprotein (LDL) levels by drug treatment, FH monocytes exposed to LPS in the absence of exogenous lipoproteins generated significantly more TNF than did control monocytes. These findings suggest that increased TNF production is not affected by hypolipidaemic treatment and may not derive from differences between uptake of exogenous LDL by FH monocytes and control cells. Chemotaxis, chemokinesis, and random migration of both FH PMN and FH monocytes were normal, as determined by agarose assay and membrane filter assay. FH PMN showed increased luminol-enhanced chemiluminescence in response to 2.5 x 10(-8) M, but not to 2.5 x 10(-6) M, N-formyl-methionyl-leucyl-phenylalanine, and not to serum-treated zymosan or to phorbol myristate acetate. Luminol- and lucigenin-enhanced chemiluminescence responses of FH monocytes were normal. In summary, the major aberration found in the present study was that FH monocytes stimulated with LPS show enhanced production of TNF. The possibility that exaggerated TNF production contributes to an early development of atherosclerotic lesions in FH subjects warrants further studies.

Adult↗
PubMed1989

Genetic polymorphism of the apolipoprotein B gene locus influences serum LDL cholesterol level in familial hypercholesterolemia.

An XbaI restriction fragment length polymorphism (RFLP) within the coding region of the apolipoprotein B (apoB) gene has been found to be associated with serum cholesterol and triglyceride levels in several populations. Mutations in another genetic locus, the low density lipoprotein (LDL) receptor gene, give rise to familial hypercholesterolemia (FH), a disease characterized by hypercholesterolemia, tendon xanthomas and atherosclerosis. We determined the XbaI genotypes and serum lipoprotein levels of 120 unrelated patients with the heterozygous form of FH. A non-parametric analysis of variance showed a significant association between elevated serum total cholesterol concentration (P less than 0.05), serum LDL-cholesterol concentration (P less than 0.025) and the presence of the XbaI restriction site (X2 allele). Thus, patients homozygous for the presence of the XbaI restriction site (genotype X2X2, n = 28) had on average a 14% higher serum total cholesterol level and a 21% higher serum LDL-cholesterol level than those homozygous for the absence of this site (genotype X1X1, n = 29); patients heterozygous for the XbaI restriction site (genotype X1X2, n = 63) had intermediate serum total and LDL-cholesterol levels. No significant differences were seen in serum triglyceride or high-density lipoprotein (HDL)-cholesterol values between these patient groups. These data demonstrate that genetic polymorphism of the principal ligand for the LDL receptor, apoB, may contribute to serum cholesterol regulation, even in patients with grossly distorted cholesterol homeostasis.

Adult↗
PubMed1989

Effects of acipimox and cholestyramine on serum lipoproteins, non-cholesterol sterols and cholesterol absorption and elimination.

The hypolipidaemic and metabolic effects of cholestyramine combined with acipimox or placebo have been evaluated in a double-blind ninety-day study in 18 patients with xanthomatous familial hypercholesterolaemia. Serum LDL-cholesterol was reduced by 35% in the cholestyramine group and 39% in the acipimoxcholestyramine group. The latter treatment increased the HDL-cholesterol level. Serum VLDL-cholesterol and triglyceride concentrations were unchanged. Cholesterol absorption efficiency was significantly reduced, and bile acid synthesis and faecal cholesterol elimination in both groups were increased. The metabolic changes were similar in the two treatment groups, but the increase in faecal neutral sterol excretion was significant only when acipimox was added. The serum cholesterol precursor sterol contents were similarly increased during the two treatments, indicating enhancement of endogenous cholesterol synthesis. The decrease in cholesterol absorption and the increase in neutral sterol excretion were more pronounced in subjects with greater than 30% than in those with less than 30% reduction in LDL-cholesterol. The changes in serum total and LDL-cholesterol levels and cholesterol metabolism were not related to apoE phenotype, but the increase in HDL-cholesterol was higher in E4 then in E3 subjects.

Adult↗
PubMed1989

Apolipoprotein E phenotype and cholesterol metabolism in familial hypercholesterolemia.

Serum lipids, lipoproteins, cholesterol absorption and parameters of cholesterol metabolism were related to apolipoprotein E phenotypes in 38 patients with familial xanthomatous hypercholesterolemia. Serum lipids and lipoproteins were similar in 2 most frequent apo E phenotypes E 3/3 and E 4/3. Coronary artery disease was not related to the apo E phenotypes. Cholesterol absorption efficiency was significantly lower in the apo E 3/3 patients than in the apo E 4/3 group. A high serum level of cholesterol precursor lathosterol, a high lathosterol/sitosterol ratio and sterol balance data suggest that cholesterol synthesis may be slightly higher in the apo E 3/3 than E 4/3 group. The findings indicate that the genetically determined apo E polymorphism contributes to cholesterol absorption efficiency in FH patients, but serum total and lipoprotein cholesterol levels are poorly related to apo E isoforms.

Apolipoproteins E↗
PubMed1989

Absorption and metabolism of cholesterol in familial hypercholesterolaemia.

1. The present study investigated the role of intestinal cholesterol absorption in the regulation of cholesterol metabolism and serum lipoprotein levels in 22 patients with heterozygous familial hypercholesterolaemia on low to normal cholesterol intake. 2. The results showed that the higher the dietary cholesterol absorption, the lower was the overall synthesis of cholesterol. Efficient cholesterol absorption actually reduced the elimination of cholesterol as faecal neutral sterols but not consistently as bile acids. 3. In multifactorial analysis, body mass index and dietary plant sterols were negatively associated with cholesterol absorption, but were unrelated to cholesterol synthesis. 4. Fractional cholesterol absorption was related only to the serum very-low-density triacylglycerol level. It was not associated with the total or low-density lipoprotein cholesterol levels. On the other hand, cholesterol synthesis was significantly associated with the serum concentrations of very-low-density lipoprotein and intermediate-density lipoprotein cholesterol and triacylglycerols, and with those of low-density lipoprotein triacylglycerols. 5. In conclusion, dietary cholesterol absorption is an essential regulator of cholesterol homoeostasis in familial hypercholesterolaemia, even in patients on low cholesterol intake.

Adult↗
PubMed1989

Peripheral atherosclerosis in familial hypercholesterolaemia.

Unlike coronary artery disease, peripheral atherosclerosis is considered to be infrequent in heterozygous familial hypercholesterolaemia. The authors studied 20 consecutive asymptomatic familial hypercholesterolaemic patients and an age- and sex-matched control group of consecutive normolipidaemic and asymptomatic patients admitted to the hospital for elective non-vascular surgery. The patients and the controls were studied non-invasively by measuring the ankle-arm systolic blood pressure ratio at rest. Peripheral atherosclerosis was common in this study population in contrast to the control group: an abnormal (less than 0.97) pressure ratio was found in 13 patients (65%) in the study group but in only one person in the control group. Eight out of 20 patients had coronary artery disease, and seven of them had an asymptomatic concomitant peripheral artery disease. Neither the classical risk factors, i.e. age, smoking, obesity, hypertension and glucose intolerance, nor serum lipid or lipoprotein status or the parameters of cholesterol metabolism correlated with peripheral atherosclerosis. It is concluded that atherosclerosis in familial hypercholesterolaemia is a multilevel disease that frequently affects also the peripheral arteries.

Adult↗
PubMed1989

Use of hospital care and hospital case-fatality of myocardial infarction during three years' follow-up in Finland.

The epidemiology and use of hospital care of myocardial infarction was studied at the population level with routinely collected hospital discharge data of the whole country during a three-year follow-up. The study population was a one-year-cohort of 13,520 patients with an acute myocardial infarction in 1981 in Finland. The incidence figures were comparable with the previous data attained from expensive and laborious special registries or population studies. With the possibility of record linkage and follow-up we could get information on the use of hospital care of these patients. We conclude that routinely collected hospital discharge data in Finland give information valuable for epidemiological studies, for the planning of health services and for the evaluation of hospital care.

Adult↗
PubMed1988

Identification of a deletion in the LDL receptor gene. A Finnish type of mutation.

A cDNA probe for the low density lipoprotein (LDL) receptor gene was used to screen DNA samples from 52 unrelated Finnish patients with the heterozygous form of familial hypercholesterolemia (FH) and 51 healthy controls. Southern blot analysis using the restriction enzyme PvuII revealed an abnormal 11 kb (kilo base-pair) restriction fragment in 16 (31%) of the patients but none of the controls. A more detailed restriction enzyme analysis of the DNA from patients revealed a mutation which apparently is due to an 8 kb deletion extending from intron 15 to exon 18 of the LDL receptor gene. Co-segregation of FH with the mutated gene was demonstrated in three families. These data are consistent with a 'founder gene effect' and support the assumption that recombinant DNA methods may have great impact on the diagnostics of FH in genetically homogeneous populations.

Adolescent↗
PubMed1988

Serum noncholesterol sterols related to cholesterol metabolism in familial hypercholesterolemia.

Serum cholesterol precursor levels and plant sterol were related to parameters of cholesterol metabolism in 22 patients with heterozygous familial hypercholesterolemia. The serum levels of cholesterol precursor sterols were inversely related to fractional absorption of dietary cholesterol and subsequently positively to overall cholesterol synthesis. The serum plant sterol levels, on the contrary, were significantly associated with fractional cholesterol absorption and negatively with overall cholesterol synthesis. These results were confirmed also with multivariate analyses. Fecal lanosterol, a cholesterol precursor, was related positively to cholesterol synthesis measured by sterol balance and serum precursors and negatively to serum plant sterols. The serum precursor and plant sterol levels were inversely significantly related to each other, indicating that the higher cholesterol absorption efficiency the higher are the serum plant sterol levels and the lower the precursor sterol contents and the overall cholesterol synthesis.

Cholesterol↗
PubMed1988

A longitudinal study of cholesterol metabolism in familial hypercholesterolemia.

Sterol balance studies were performed in 11 patients with familial hypercholesterolemia before and after a 15-year follow-up exactly under the same conditions to evaluate whether ageing exerts any changes on serum lipids and cholesterol metabolism. No significant intraindividual variation could be observed in serum lipids, bile acid and cholesterol synthesis and cholesterol excretion as neutral sterols and no age-related association could be observed in these parameters.

Adult↗
PubMedDate not supplied

Dyslipidemia and a reversible decrease in insulin sensitivity induced by therapy with 13-cis-retinoic acid.

BACKGROUND: 13-cis-Retinoic acid (Roaccutan) treatment is associated with disturbances in lipid and sometimes also in glucose metabolism. Thus, we investigated whether 13-cis-retinoic acid treatment decreases insulin sensitivity. METHODS: We studied 11 men [aged 24+/-2 years (mean+/-SEM), body mass index (BMI) 22.1+/-0.9 kg/m(2)] who received Roaccutan treatment for acne for a period averaging 5 months but who were otherwise healthy. The insulin sensitivity of the subjects was measured before, during and 1-3 months after the end of treatment using the euglycaemic hyperinsulinaemic clamp technique. RESULTS: Treatment with 13-cis-retinoic acid reduced total (59+/-4 vs 55+/-4 micromol/kg/min, p<0.02), oxidative (25+/-1 vs 22+/-2 micromol/kg/min, p<0.05) and non-oxidative (36+/-3 vs 33+/-3 micromol/kg/min, p=0.05) glucose disposal rate, and there was a 4% increase in HbA(1c) (from 5.2+/-0.07 to 5.4+/-0.07%, p<0.02). After treatment cessation these values returned to baseline. 13-cis-Retinoic acid treatment also resulted in increased very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol, increased VLDL triglyceride, and increased VLDL and LDL phospholipid concentrations. CONCLUSION: Treatment of acne with 13-cis-retinoic acid reduces insulin sensitivity and induces alterations in lipid metabolism resembling those of the insulin resistance syndrome.

Acne Vulgaris↗