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Biomedical subjects

H Gylling

Publications and source records attributed to H Gylling.

At least 91 records · Page 5Linked to original sources
PubMed1995

Sitostanol ester margarine in dietary treatment of children with familial hypercholesterolemia.

In familial hypercholesterolemia (FH) the lowering of serum cholesterol levels should be started in childhood in order to prevent coronary artery disease later in life. However, treatment of children is problematic. We studied the effects of sitostanol (3 g/day) ester dissolved in rapeseed oil margarine as a hypocholesterolemic agent in one homozygous and 14 heterozygous children with FH maintained on a low cholesterol diet for 6 weeks, using a double-blind crossover design. Absorption and synthesis of cholesterol were evaluated by measuring serum plant sterol and cholesterol precursor proportions to cholesterol by gas-liquid chromatography. The compliance was good, and the children could not distinguish by taste the two margarines without and with sitostanol ester. Sitostanol margarine significantly reduced serum total, intermediate density (IDL), and low density lipoprotein (LDL) cholesterol by 11, 26, and 15%, respectively, and increased HDL/LDL cholesterol ratio by 27%. The proportions of serum delta 8-cholestenol, lathosterol, and desmosterol were significantly increased by 36, 19, and 18%, and those of serum cholestanol, campesterol, and sitosterol were significantly decreased by 9, 42 and 29%, respectively, suggesting that cholesterol absorption was decreased and synthesis was compensatorily increased. High basal precursor sterol proportions predicted a high decrease in LDL cholesterol levels. In conclusion, partial replacement of normal dietary fat consumption by sitostanol ester margarine appears to be an effective and safe hypocholesterolemic treatment in children with FH.

Adolescent↗
PubMed1995

Metabolism of cholesterol and low- and high-density lipoproteins in primary biliary cirrhosis: cholesterol absorption and synthesis related to lipoprotein levels and their kinetics.

Cholesterol absorption, elimination, and synthesis, and low-density lipoprotein (LDL) and high density lipoprotein (HDL) kinetics were studied in patients with mild to severe primary biliary cirrhosis (PBC) (n = 16) to show how this cholestatic disease modified cholesterol and lipoprotein metabolism as compared with healthy controls (n = 50). Serum total and lipoprotein cholesterol and triglyceride levels were similar in the two groups, but in PBC, especially in severe forms, very low density lipoprotein (VLDL) was rich in apoprotein (apo) B and cholesterol and low in triglycerides, whereas LDL was rich in triglycerides and low in esterified cholesterol, and HDL was enriched by surface lipids, phospholipids, and free cholesterol. In severe PBC, the fractional catabolic rate (FCR) for LDL apo B was reduced. The transport rate (TR) for LDL apo B was unaffected and it tended to correlate with the LDL apo B and LDL cholesterol levels in PBC, whereas in the controls the LDL apo B concentration was regulated by both the FCR and TR, and LDL cholesterol was regulated only by FCR. FCR for apo A-I in HDL was unaltered in PBC, but TR for apo A-I was reduced in the severe cases. Cholesterol absorption efficiency was significantly reduced in PBC (14.5 +/- 3.0% in severe PBC and 34.0 +/- 2.5% in mild PBC vs. 47.4 +/- 1.4% in the controls, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1994

Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment.

Cholesterol absorption and metabolism and LDL and HDL kinetics were investigated in 11 hypercholesterolaemic non-insulin-dependent diabetic men off and on a hypolipidaemic treatment with sitostanol ester, (3 g sitostanol daily) dissolved in rapeseed oil margarine, by a double-blind crossover study design. Serum total, VLDL and LDL cholesterol and apoprotein B fell significantly by 6 +/- 2, 12 +/- 6, 9 +/- 3 and 6 +/- 2%, mean +/- SEM, and HDL cholesterol was increased by 11 +/- 4% (p < 0.05) by sitostanol ester. LDL cholesterol and apoprotein B were significantly decreased in the dense (1.037-1.055 g/ml), but not light, LDL subfraction due to a significantly diminished transport rate for LDL apoprotein B, while the fractional catabolic rate was unchanged. HDL kinetics, measured with autologous apoprotein A I, was unaffected by sitostanol ester. Cholesterol absorption efficiency was markedly reduced from 25 +/- 2 to 9 +/- 2% (p < 0.001) during sitostanol ester followed by proportionately decreased serum plant sterol proportions. Cholesterol precursor sterol proportions in serum, fecal neutral sterol excretion, and cholesterol synthesis, cholesterol transport, and biliary secretion were all significantly increased by sitostanol ester. We conclude that the sitostanol ester-induced decrease in cholesterol absorption compensatorily stimulated cholesterol synthesis, had no effect on fractional catabolic rate, but decreased transport rate for LDL apoprotein B so that serum total, VLDL and LDL cholesterol levels were decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins A↗
PubMed1994

Postabsorptive metabolism of dietary squalene.

Serum squalene, a non-steroid intermediate of cholesterol biosynthesis, originates mainly from endogenous cholesterol synthesis and partly from diet, especially in populations consuming a lot of olive oil rich in squalene. Its postabsorptive metabolism has not been studied in detail in humans. Its presence in chylomicrons and VLDL suggests that the removal of dietary squalene may reflect the metabolism of intestinal lipoproteins. Accordingly, we studied the postabsorptive metabolism of 1 g dietary squalene in 16 healthy subjects with apolipoprotein (apo) E 3/3 phenotype and in five type III hyperlipidemic apo E 2/2 homozygotes known to have a retarded chylomicron remnant removal, and compared the results with vitamin A fat load test. About 40% of the basal and 90% of the postabsorptive squalene was in lipoproteins < 1.019 g/ml. The peak concentrations of chylomicron squalene were at 6 h, and of triglyceride-rich nonchylo-fraction at 9-12 h in the controls. The peak values occurred later than those of vitamin A. At 24 h the levels still exceeded the basal ones. In type III dyslipoproteinemia, most of the basal and postabsorptive squalene was in lipoproteins of density less than 1.019 g/ml, the peak postabsorptive values occurred later than in the controls and the serum values remained above the control levels for up to 24 h. The squalene and vitamin A areas under the incremental response curves (AUC) were higher than in the control group. The AUCs of the two markers in chylomicron were correlated negatively and those in LDL+HDL were correlated positively with fasting HDL cholesterol levels, the respective correlations being opposite with fasting VLDL triglycerides. The postabsorptive profile of squalene levels resembled that of vitamin A in both groups, except that the squalene curves were shifted to a later time period. Thus, a delayed clearance of chylomicron remnants could be detected by analyzing serum squalene 6-24 h after the squalene-supplemented fat meal.

Adult↗
PubMed1994

Regulation of serum cholesterol level in middle-aged and elderly men. Relation of cholesterol absorption and synthesis to lipoprotein metabolism.

The aim of the present study was to investigate cholesterol absorption and cholesterol and bile acid synthesis and relate these values of kinetics of low-density lipoprotein (LDL) apoprotein (apo) B in 50- and 75-year-old men to find out why and by which mechanism serum cholesterol level decreases with advancing age under normal home-living conditions. The daily calorie, fat, and cholesterol intakes were lower in the 75-year-old men because the physiological requirements of daily energy are reduced in old age. However, absolute body weight was identical in the two groups, indicating isocaloric energy intake. Serum levels of total and LDL cholesterol were insignificant lower but those of LDL apo B significantly lower, so that the LDL cholesterol/apo B ratio was higher in the elderly men. The mean reduction of LDL apo B by 26% (P < .05) in the old men was associated with a 30% (P < .05) decrease in transport rate (TR) and a 3% (P = NS) decrease in removal (FCR) for LDL apo B. However, at the comparable apo B levels, both TR and FCR for apo B were significantly lower in the old than in the younger men. Cholesterol absorption efficiency, bile acid synthesis, fecal neutral and total sterol excretion, and cholesterol turnover but not synthesis were reduced in the elderly men.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1994

Cholesterol absorption and cholesterol and bile acid synthesis in two brothers with IDDM and diarrhea.

OBJECTIVE: To determine the best possible treatment for two brothers who had IDDM and bile acid malabsorption-associated disabling diarrhea that was resistant to cholestyramine, antibiotics, clonidine, loperamide, or anticholinergic drugs. RESEARCH DESIGN AND METHODS: Our study paired these two brothers with control subjects. Serum noncholesterol sterols and fecal elimination of cholesterol and plant sterols were quantitated by gas-liquid chromatography. RESULTS: Fecal losses of bile acids exceeded four to six times the control values, and cholesterol synthesis was increased two to three times. Cholesterol absorption efficiency and serum cholesterol concentrations were, respectively, within the high and low control range. CONCLUSIONS: Bile acid malabsorption might have resulted from deranged intestinal motility, possibly contributed by gastrointestinal neuropathy, and some genetic factor.

Adult↗
PubMed1993

Metabolism of cholesterol and apolipoprotein B in celiac disease.

To test the association of cholesterol malabsorption with cholesterol and lipoprotein metabolism, we determined low-density lipoprotein (LDL) apolipoprotein (apo) B kinetics simultaneously with measurements of cholesterol absorption and synthesis in six patients with celiac disease (CD) before and during the gluten-free diet (GFD). The basal condition was characterized by low cholesterol absorption, enhanced cholesterol synthesis, and high removal and transport rate of LDL apo B. The GFD markedly improved cholesterol absorption and decreased intestinal influx of cholesterol, fecal neutral steroids, and cholesterol synthesis. Of plasma total and lipoprotein cholesterol levels, only plasma high-density lipoprotein (HDL) was enhanced by the GFD proportionately to cholesterol absorption. The plasma LDL apo B level remained unchanged because of simultaneous decreases in the fractional catabolic rate (FCR) and transport rate of LDL apo B. In fact, the more cholesterol absorption was improved by the GFD, the more the FCR and transport rate for LDL apo B were decreased, and their reductions were closely related to the decrease in cholesterol synthesis. The present results show that cholesterol absorption, cholesterol synthesis, hepatic B/E receptor activity, and LDL apo B transport rate are closely associated with each other and that their levels can change markedly with no detectable change in serum levels of LDL cholesterol or apo B.

Absorption↗
PubMed1993

Postabsorptive retinyl palmitate removal is retarded in lecithin-cholesterol acyltransferase deficiency.

Postabsorption fat clearance of intestinal lipoproteins indicated by retinyl palmitate was studied in two siblings with the classical lecithin-cholesterol acyltransferase (LCAT) deficiency and in a control group of 21 healthy subjects with similar apoprotein E 3/3 phenotype. Relatively high pre- and postabsorptive cholesterol esterification percentage of chylomicrons suggested that acyl coenzyme A:cholesterol acyltransferase activity was not inhibited. Postabsorptive levels of plasma lipids increased and decreased roughly similarly in the cases and controls with the postabsorptive peak values at about 4 h. Plasma total and chylomicron levels of retinyl palmitate were not affected by LCAT deficiency, while the removal of the vitamin from very low and intermediate density lipoproteins was clearly reduced so that the peak concentrations, values under the response curves and the time of the peak concentrations were markedly higher than in the controls. The long-lasting circulation of chylomicron remnants of density < 1.006-1.019 g ml-1 may have some clinical significance because postabsorptive lipoproteins are suspected to have atherogenic potentiality.

Aged↗
PubMed1993

Deletion of exon 15 of the LDL receptor gene is associated with a mild form of familial hypercholesterolemia. FH-Espoo.

We describe a mutation of the low-density lipoprotein (LDL) receptor gene, designated familial hypercholesterolemia (FH)-Espoo, which deletes exon 15 of the LDL receptor gene. The mutant receptor is predicted to lack 57 amino acids, including 18 serine and threonine residues, which are the sites of the clustered O-linked sugars of the receptor. Studies on 10 carriers of this gene revealed that FH-Espoo is associated with an exceptionally mild form of FH. Thus, in conditions in which cell proliferation was rendered dependent on the function of LDL receptors, lymphocytes from the patients with the FH-Espoo allele had a growth rate intermediate between those from healthy subjects and patients with the FH-Helsinki gene, a mutation known to abolish LDL receptor function. The in vivo fractional catabolic rate of LDL apolipoprotein B was lower than normal in the two FH-Espoo heterozygotes studied. Although higher than those in healthy controls, the serum LDL cholesterol concentrations in patients with the FH-Espoo gene were significantly lower than those in patients with the FH-Helsinki mutation. The thickness of the Achilles tendons was within the normal limits in subjects with the FH-Espoo gene. Our study suggests that moderate varieties of hypercholesterolemia, ie, those not considered to represent FH, may occasionally be due to subtle LDL receptor gene mutations.

Adolescent↗
PubMed1993

Effects of ketoconazole on cholesterol precursors and low density lipoprotein kinetics in hypercholesterolemia.

Ketoconazole, an inhibitor of cholesterol synthesis at 14 alpha-demethylation of lanosterol, effectively reduces serum total and low density lipoprotein (LDL) cholesterol levels. We studied the effects of ketoconazole (400 mg/day for 5 weeks) on serum lipids, free and esterified noncholesterol sterols, and kinetics of LDL apolipoprotein B (apoB) in seven patients with heterozygous familial hypercholesterolemia (FH) and in three patients with primary hypercholesterolemia (nonFH). The total, intermediate density, and LDL cholesterol levels were significantly reduced by 24, 27, and 29%, respectively, and LDL apoB by 23%. Serum total and lipoprotein triglycerides were unchanged. The LDL cholesterol/apoB ratio decreased significantly. Serum ratios of lanosterols to cholesterol were increased over 50 times, almost the same in all lipoproteins and mainly as the unesterified form; free delta 8-precursor sterols, 2-5 times; cholestanol, slightly; while ratios of lanosterol of desmosterol, lathosterol, and plant sterols were virtually unchanged. Inconsistent esterification of methyl sterols might indicate unaltered acyl CoA:cholesterol acyltransferase activity. LDL apoB transport was decreased in all nonFH subjects but inconsistently in FH. The fractional catabolism rate (FCR) for LDL apoB was increased significantly in FH by 13% and inconsistently by 4% in nonFH. In a subgroup of three FH patients, more dense LDL (d 1.037-1.055 g/ml) was transported and catabolized faster on than off ketoconazole so that the serum level of this more dense LDL subfraction was unchanged, the decrease of LDL being due to a reduction of the less dense LDL subfraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins B↗
PubMed1992

Non-cholesterol sterols, absorption and synthesis of cholesterol and apolipoprotein A-I kinetics in a Finnish lecithin-cholesterol acyltransferase deficient family.

We describe the first Finnish LCAT-deficient family with two affected, one questionably affected and one healthy family member. The affected family members presented stomatocytes in the peripheral blood, exhibited low serum levels of total, LDL and HDL cholesterol, triglycerides, phospholipids and apolipoprotein A-I and especially A-II. Apolipoprotein A-I catabolism was accelerated to moderately high and very high levels in the two affected subjects. Cholesterol esterification percentage was low in all lipoprotein fractions. The intestinal cholesterol absorption efficiency and cholesterol and bile acid synthesis were within normal limits. The esterification percentage of demethylated cholesterol precursor sterols, cholestanol and plant sterols resembled mostly that of cholesterol, while those of VLDL and LDL methostenols, precursor sterols esterified by acyl-CoA:cholesterol acyltransferase (ACAT), suggested normal ACAT activity. In HDL all sterols were poorly esterified. The observations on stomatocytes, normal absorption and synthesis of cholesterol and bile acids, abnormal kinetics of apolipoprotein A-I, evidence of normal ACAT activity and abnormal esterification of non-cholesterol sterols are findings presented for the first time in LCAT deficiency.

Absorption↗
PubMed1992

Prevalence and geographical distribution of major LDL receptor gene rearrangements in Finland.

In order to determine the prevalence of major rearrangements of the low density lipoprotein (LDL) receptor gene in Finland, DNA samples of 199 unrelated Finnish patients with the heterozygous form of familial hypercholesterolaemia (FH) were examined by Southern blot analysis. The FH-Helsinki mutation, characterized by a 9.5-kb deletion in the 3'-end of the LDL receptor gene, was found in 75 (38%) of the patients. The prevalence of this mutation ranged from 26-58% in different areas of Finland. A striking exception was the North Karelia region, where only one out of 26 (4%) FH patients was found to carry the FH-Helsinki allele. Two patients were found to carry other types of large nucleotide rearrangements of the LDL receptor gene. One mutation was a 7.5-kb deletion eliminating exons 7 to 10, and the other was a 13-kb deletion covering exons 11 to 16 of the LDL receptor gene. Serum lipoprotein levels were very similar in each category of mutation, i.e. in patients with the FH-Helsinki gene, those with the two other types of deletion, and the remaining patients with as yet unknown types of LDL receptor gene defects. These results show that, even in genetically uniform populations, FH may be heterogeneous at the DNA level. DNA techniques enable an unequivocal diagnosis for almost 40% of the Finnish patients with the heterozygous form of FH.

Blotting, Southern↗
PubMed1992

Persistence of abnormalities in metabolism of apolipoproteins B-100 and A-I after weight reduction in patients with primary hypertriglyceridemia.

Obesity commonly accompanies hypertriglyceridemia, and weight reduction is widely recommended for treatment of elevated triglyceride levels. To determine whether weight reduction will normalize lipoprotein metabolism in overweight, hypertriglyceridemic patients, 10 such male patients underwent weight loss until their body weights were within the desirable range. After reestablishment of a steady state in body weight at the lower level, measurements were made of plasma lipid, lipoprotein, and apolipoprotein levels and the kinetics of low density lipoprotein (LDL) apolipoprotein B-100 (apo B) and apolipoprotein A-I (apo A-I). The patients lost an average of 10.6 +/- 2.1 kg (mean +/- SEM). Plasma triglyceride concentrations fell from 431 +/- 42 mg/dl to 248 +/- 27 mg/dl (p less than 0.001), whereas concentrations of total cholesterol, LDL cholesterol, total apo B, and high density lipoprotein (HDL) cholesterol were unchanged after weight loss. On average, the fractional catabolic rates (FCRs) for LDL were much higher in the patients after weight loss than in 16 normal control subjects (0.55 +/- 0.06 versus 0.31 +/- 0.06 pool/day), and input rates for LDL also were higher for hypertriglyceridemic patients after weight loss (22.2 +/- 2.4 versus 12.8 +/- 2.3 mg/kg.day). Compared with 20 normal control subjects, hypertriglyceridemic patients after weight reduction had persistent low HDL cholesterol levels (32 +/- 2 versus 54 +/- 3 mg/dl) as well as low apo A-I levels (99 +/- 5 versus 122 +/- 4 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Cholesterol absorption, elimination, and synthesis related to LDL kinetics during varying fat intake in men with different apoprotein E phenotypes.

Cholesterol absorption, fecal elimination, and synthesis and low density lipoprotein (LDL) metabolism were measured in 29 middle-aged men while on their normal diet and a diet low in fat and cholesterol, and the obtained values were related to apoprotein (apo) E phenotypes. Basal cholesterol absorption efficiency was positively related to production rate (PR) for LDL apo B and negatively to cholesterol synthesis (measured by fecal steroids and dietary cholesterol), which in turn was negatively associated with the LDL level and positively with the fractional removal (FCR) of LDL apo B. The apo E subscript (e.g., E2/2 = 1, E2/3 = 2, etc.) was positively associated with cholesterol absorption and the LDL apo B and cholesterol levels and negatively with cholesterol synthesis and FCR for LDL apo B. Effective bile acid and cholesterol synthesis, fecal elimination of cholesterol, removal of LDL apo B, and low cholesterol absorption characterized men with the epsilon 2 allele. Reduction of dietary fat and cholesterol intakes lowered LDL cholesterol levels and cholesterol absorption but increased cholesterol synthesis proportionally to the apo E subscript; the FCR and PR for LDL apo B were significantly increased and decreased, respectively. The decrease in absorption was related to enhanced removal of LDL apo B and synthesis of cholesterol. During the modified diet, cholesterol metabolism was poorly related to LDL, apo E phenotypes, and LDL apo B kinetics. A positive correlation of cholesterol absorption with dietary fat intake in combined studies suggests that a dietary fat reduction-associated decrease in LDL cholesterol is at least partly caused by reduced cholesterol absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗