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Biomedical subjects

K Kervinen

Publications and source records attributed to K Kervinen.

51 records · Page 3Linked to original sources
PubMed1993

Lovastatin enhances hepatic uptake of low density lipoprotein in humans.

A noninvasive method for visualizing the uptake of low density lipoprotein (LDL) was used to investigate the effect of hypolipidemic drugs on LDL uptake by the human liver in vivo. Fourteen hypercholesterolemic patients (six with familial hypercholesterolemia and eight with common hypercholesterolemia) were studied. Autologous LDL particles were isolated and divided into two aliquots; one was labeled with 99mTC and the other with 131I, and both preparations were reinjected simultaneously. The labeled LDL was visualized 24 h later by scanning the thorax and abdomen with a gamma camera, and the liver/heart ratio was calculated as an estimate of the hepatic uptake of LDL. The results of 99mTC-labeled LDL scintigraphy were compared with conventional determinations of the fractional catabolic rate (FCR) for 131I-labeled LDL. The latter correlated best with the liver/heart ratio (r = 0.80, P < 0.001). Lovastatin treatment increased the liver/heart ratio (15%, P < 0.01) in the patients with polygenic hypercholesterolemia and the FCR for LDL in both groups (22%, P < 0.05, for those with familial hypercholesterolemia and 37%, P < 0.01 for those with polygenic hypercholesterolemia). Scanning of the liver using the 99mTC-labeled LDL method provides a noninvasive method for visualizing the hepatic uptake of LDL in vivo in humans. This study also provides direct proof that lovastatin, a drug that enhances LDL receptor activity in the liver, also increases the hepatic uptake of LDL in humans.

Adult↗
PubMed1992

Carbamylation-induced alterations in low-density lipoprotein metabolism.

Low-density lipoprotein was derived from carbamyl (carbamyl-LDL) by incubating LDL in potassium cyanate (KCNO). The proportion of free amino groups in the carbamyl-LDL was negatively correlated (r = -0.95) with the time of incubation in potassium cyanate (ranged from 5 to 360 min). The carbamylation did not change the chemical composition or the flotation characteristics of the LDL particles. However, the electrophoretic mobility of carbamyl-LDL was distinctly increased with the extent of carbamylation. The carbamyl-LDL had substantially decreased binding to the LDL apoB/E receptors of the bovine adrenocortical membranes when compared to the control-LDL. The reduced binding was already observed when only 9% of the free amino groups were derived from carbamyl. A minor carbamylation of LDL (less than 20% of the free amino groups) decreased the in vivo clearance of LDL from rabbit plasma. However, when more than 20% of the free amino groups were derived the carbamyl-LDL had accelerated clearance compared to the control-LDL. LDL isolated from uremic patients was cleared in rabbits at a slower rate than LDL isolated from a control subject. Providing that carbamylation of LDL could also occur in vivo resulting in similar alterations of the LDL binding to the LDL B/E receptors, as observed in the present study, the uremia-related accelerated atherosclerosis could have one additional mechanistic explanation.

Adrenal Cortex↗
PubMed1992

A controlled study on the effect of beta-glucan-rich oat bran on serum lipids in hypercholesterolemic subjects: relation to apolipoprotein E phenotype.

The effects of beta-glucan-rich oat bran on serum lipids and lipoproteins were examined in a randomized 8-week study. After a 4-week run-in phase, subjects with mild to moderate hypercholesterolemia [serum total cholesterol (TC) 5.5-8.5 mmol/l] on cholesterol-lowering diets were randomly allocated to an oat bran (10.3 g beta-glucan/day) or wheat bran group. Thirty-six subjects (20 in the oat bran group, 16 in the wheat bran group) completed the study. The diet was identical in both groups during the trial and no significant changes in body weight were found. Serum TC and low-density lipoprotein cholesterol (LDL-C) significantly declined in the oat bran group during the first 4 weeks from 7.03 +/- 0.81 to 6.72 +/- 0.97 (p = 0.028) and from 4.90 +/- 0.69 to 4.61 +/- 0.89 mmol/l (p = 0.038), respectively, but at 8 weeks the values were not significantly different from baseline. Changes in serum TC were mainly confined to those who ate at least two-thirds of the planned daily dose of oat bran. In wheat bran group no changes were observed in serum TC or LDL-C levels. Apolipoprotein A1 and B did not change significantly in either group. Only subjects with apolipoprotein E 3/3 phenotype (n = 12) had hypocholesterolemic response to oat bran at 4 weeks, but no change was found in those with apolipoprotein E 4/4 or 4/3 (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Multiple metabolic syndrome: aspects of genetic epidemiology and molecular genetics.

Epidemiological studies have documented the association between cardiovascular disease and high blood pressure, dyslipidaemia, impaired glucose tolerance, non-insulin-dependent diabetes mellitus (NIDDM), and central obesity. In fact, several of these abnormalities, often all of them, can be identified in the very same individuals, constituting the entity of the multiple metabolic syndrome. Furthermore, many of these abnormalities seem to run in families. These findings raise important questions about the genetic epidemiology of the disease and about the molecular genetic background of the most likely common nominator of this syndrome, namely insulin resistance. Therapeutic actions must also be carefully considered to avoid the encouragement of some abnormalities while treating others.

Apolipoproteins E↗
PubMed1991

Relation of coronary heart disease and apolipoprotein E phenotype in patients with non-insulin dependent diabetes.

OBJECTIVES: To examine the relation between coronary heart disease and the apolipoprotein E phenotypes in patients with non-insulin dependent diabetes mellitus. DESIGN: Cross sectional study. SETTING: District around Kuopio University Central Hospital, East Finland. SUBJECTS: 138 men with non-insulin dependent diabetes and 64 men without diabetes as controls. MAIN OUTCOME MEASURE: Apolipoprotein E phenotype, electrocardiographic abnormalities, other signs of coronary heart disease. RESULTS: The prevalences of definite myocardial infarction and ischaemic electrocardiographic changes were highest in the diabetic men with the phenotypes E4/4 or E4/3 (25% (95% confidence interval 18% to 32%) and 50% (42% to 58%) respectively), although the difference between the phenotype groups was not significant. The prevalence of angina pectoris was 69% (61% to 77%) in men with the phenotypes E4/4 or E4/3 (p = 0.005 compared with other phenotypes), 41% (33% to 49%) in men with phenotype E3/3, and 47% (39% to 55%) in those with phenotypes E2/2 or E2/3. Similarly, the simultaneous presence of angina pectoris and ischaemic electrocardiographic changes was highest in the diabetic men with the phenotypes E4/4 or E4/3 (42% v 22% in those with E3/3 and 29% in those with E2/2, E2/3; p = 0.038). Overall, the prevalence of any evidence of coronary heart disease among the diabetic subjects with the phenotypes E4/4 or E4/3 was 81% (p = 0.011 compared with other phenotypes), 58% in those with phenotype E3/3, and 53% in those with phenotypes E2/2 or E3/3. CONCLUSION: Apolipoprotein E phenotypes E4/4 and E4/3 modulate the risk of coronary heart disease in men with non-insulin dependent diabetes.

Angina Pectoris↗
PubMed1991

Magnitude of dietary effects on plasma cholesterol concentration: role of sex and apolipoprotein E phenotype.

The effects of fat-controlled, low-cholesterol and high-fat, high-cholesterol diets pursued for 4 weeks on plasma lipids and lipoproteins were studied in 44 healthy middle-aged subjects (22 women and 22 men). All the calories were supplied from the hospital kitchen. When the subjects were switched from the fat-controlled, low-cholesterol diet to the high-fat, high-cholesterol diet the average increase in total cholesterol was 1.2 mmol/l (28%), ranging from 0.2 to 2.7 mmol/l (4-56%). At the same time the average increase in LDL cholesterol was 1.0 mmol/l (39%), ranging from 0.1 to 2.4 mmol/l (3-90%). Interestingly, the men responded to the dietary changes more sensitively than the women. The increase in total cholesterol from the low-fat to the high-fat diet was 31% for the men and 25% for the women (P less than 0.05), the corresponding increases in LDL cholesterol being 42% and 37%, respectively (P less than 0.05). A marked increase in HDL cholesterol was observed when the subjects were switched from the low-fat to the high-fat diet, the increase being 30% for the men and 20% for the women. The absolute and percentage lipid changes on the two diets were equal in the subjects with the common apolipoprotein E phenotype 3/3 and in those homozygous and heterozygous for the epsilon 4 allele (E4/4 and E4/3).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

A rapid increase in lipoprotein (a) levels after ethanol withdrawal in alcoholic men.

Plasma concentrations of lipoprotein (a) (Lp(a)) were studied in 11 male alcoholics at the end of a drinking period and monitored during subsequent abstinence. Lp(a) levels showed a daily increase for four consecutive days after the beginning of abstinence, the values for the third and the fourth day being significantly higher than those of the first day (p less than 0.05 and p less than 0.01, respectively). The changes in Lp(a) showed no association with the changes in low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol levels. In one alcoholic subject with a heterozygous form of familial hypercholesterolemia who was monitored for 11 days, the Lp(a) levels rose up to the fourth day and remained at a high level thereafter. These results suggest that ethanol ingestion may be associated with a lowering of Lp(a) levels, which may contribute to the delayed progression of atherosclerosis observed in alcohol drinkers. Ethanol intake may be added to the short list of factors that affect the quite stable, genetically determined Lp(a) concentrations in the plasma.

Alcoholism↗
PubMed1991

Low density lipoprotein derivatization by acetaldehyde affects lysine residues and the B/E receptor binding affinity.

Acetaldehyde (AcA), the first metabolite in ethanol oxidation, forms covalent adducts with the free amino groups of various proteins. In this study, we examined how acetaldehyde modification affects the chemical and biological properties of the atherogenic low density lipoprotein (LDL). AcA modification did not alter the protein and lipid composition of LDL, but the AcA concentration used in the incubation correlated strongly with the electrophoretic mobility of acetaldehyde-treated LDL (AcA-LDL) (r = 0.97, p less than 0.001) and the percentage of the free amino groups in AcA-LDL (r = -0.90, p less than 0.01). Amino acid analysis of AcA-LDL showed that lysine was the predominant residue in LDL modified by AcA. Assays with monoclonal antibodies (MB47, 2b, 4G3, and C1.1) directed against different epitopes of the LDL apoprotein B suggested that AcA modification reduced the immunological recognition of the LDL receptor binding region and its vicinity. Also, the binding affinity of AcA-LDL to B/E receptors correlated negatively with the percentage of modified lysine residues in AcA-LDL (r = -0.96, p less than 0.001). The results suggest that AcA derivatizes the lysine residues of LDL, and thus decreases the B/E receptor binding affinity of LDL. However, major changes in LDL receptor binding were produced only with non-physiologically high concentrations of AcA, and, therefore, the role of the present findings in vivo remains uncertain.

Acetaldehyde↗
PubMed1991

Multiple changes in apoprotein B containing lipoproteins after ethanol withdrawal in alcoholic men.

The plasma concentrations and chemical compositions of the apolipoprotein B containing lipoproteins (VLDL, IDL and LDL) were studied in 29 male alcoholic subjects at the end of a drinking period and in 17 healthy controls. No difference was found in the concentrations of plasma total cholesterol and triglyceride between the alcoholics and the controls, whereas plasma HDL cholesterol and VLDL triglycerides were 90% and 73%, respectively, higher in the alcoholics. The VLDL cholesterol:triglyceride ratio was reduced by 32%, whereas VLDL protein:cholesterol and phospholipid:cholesterol ratios were increased by 36% and 46%, respectively. IDL mass and protein concentrations, and particularly the fractional cholesteryl ester content of IDL tended to be low in the alcoholics. The plasma concentrations of all the LDL components except triglycerides were reduced in the alcoholics, resulting in a lower LDL cholesterol:triglyceride ratio. During the four day abstinence, when the lipoprotein values were followed in 15 alcoholic subjects, the abnormalities in VLDL composition and LDL plasma concentrations changed towards the values of the controls. In six alcoholic subjects who volunteered for LDL kinetic studies the fractional catabolic rate for LDL particles isolated immediately after the drinking period and seven days later were the same. These studies suggest that the alterations in all the apoB containing lipoproteins may contribute to the delayed progression of atherosclerosis observed in alcohol users.

Adult↗
PubMed1990

Increased high-density lipoprotein cholesterol concentration in alcoholics is related to low cholesteryl ester transfer protein activity.

Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl esters from HDL to apoB-containing lipoproteins. Since alcoholics have high HDL cholesterol and low LDL cholesterol levels, a defect in cholesteryl ester transfer could be responsible for the alcohol-induced alteration in cholesterol distribution between lipoproteins. To test this hypothesis, we compared CETP activity in plasma from 30 alcoholics without severe liver damage and 16 control subjects. Plasma CETP activity was 28% lower in the alcoholics compared with the controls (P less than 0.001), while the teetotallers among the latter had slightly higher CETP activity than those who consumed alcohol in moderation. CETP activity increased slowly after ethanol withdrawal, but did not reach the control level within the 7-day observation period. A positive correlation was observed between plasma CETP activity and the LDL cholesterol HDL cholesterol ratio (r = 0.480, P less than 0.002), whereas CETP activity showed a negative correlation with HDL cholesterol level (r = -0.467, P less than 0.001). The results indicate that defective transfer of cholesteryl esters from HDL to LDL contributes to the high HDL cholesterol levels in alcoholics.

Alcoholism↗
PubMed1987

Acetaldehyde modification of low density lipoprotein accelerates its catabolism in man.

Acetaldehyde (AcA), the first metabolite in ethanol oxidation, is chemically highly reactive and binds covalently to the free amino groups of various proteins. In this study, we examined the metabolism of acetaldehyde-modified LDL (AcA-LDL) in man. LDL was isolated from human volunteers, radiolabelled with either 125I or 131I, incubated in various AcA concentrations (Aca-LDL) and injected back into the donors simultaneously with LDL incubated in identical conditions but omitting AcA (C-LDL). Acetaldehyde treatment did not change the chemical composition, electrophoretic mobility or the flotation characteristics of LDL. The proportion of free amino groups of AcA-LDL, ranging from 97 to 54.5%, was negatively correlated with the final concentration of AcA used in the incubation medium (r = -0.99, P less than 0.001). AcA modification of LDL accelerated its in vivo catabolism in man in such a way that the fractional catabolic rate (FCR) for AcA-LDL was negatively correlated with the percentage of free amino groups in AcA-LDL (r = -0.87, P less than 0.01). The clearance of AcA-LDL modified in 0.4, 2.0, 4.0 and 8.0 mM AcA was 0.9, 1.4, 2.5 and 3.7 times faster than the clearance of C-LDL, respectively. If AcA-LDL is formed in man after ethanol ingestion, its rapid clearance may be one possible mechanism for the low LDL levels observed in chronic alcohol users.

Acetaldehyde↗
PubMedDate not supplied

Modification of VLDL apoprotein B by acetaldehyde alters apoprotein B metabolism.

Acetaldehyde (AcA), the first metabolite in ethanol oxidation, is chemically highly reactive and forms adducts with proteins in alcoholics. We examined the effect of very low density lipoprotein (VLDL) apoprotein B (apoB) modification by AcA on the metabolism of apoB-containing lipoproteins [VLDL, intermediate density lipoprotein (IDL) and low density lipoprotein (LDL)]. VLDL-B was selectively radiolabelled with either 125I or 131I and modified with various AcA concentrations, and the preparation was injected into rabbits simultaneously with control-treated VLDL. AcA modification of VLDL-B reduced the fractional catabolic rates for VLDL-B, IDL-B, and LDL-B. The direct removal of VLDL-B from plasma was decreased, whereas the fraction of VLDL-B converted to IDL-B was increased. The effect of AcA modification on the overall fraction of VLDL converted to LDL was qualitatively heterogeneous: VLDL-B modification with 2.0 mM AcA reduced the fraction converted, whereas modification with 4.0 and 8.0 mM AcA increased it. The concentrations of AcA used were higher than those reported in blood after ethanol ingestion, but the experiments serve to test in qualitative terms the model of VLDL-B modification by AcA. The observed VLDL-B alteration by AcA in vivo in alcoholics is most likely to be close to the minor modification used here, thereby theoretically contributing to the low IDL and LDL levels observed in alcoholics.

Acetaldehyde↗
PubMedDate not supplied

Apolipoprotein E phenotype alone does not influence survival in Alzheimer's disease: a population-based longitudinal study.

Apolipoprotein E4 (ApoE4) phenotype is a known risk factor for development of Alzheimer's disease (AD). Contradictory results exist concerning the role of ApoE4 in the rate of decline and mortality in AD. Conflicting findings have also been reported about ApoE and gender interactions with respect to survival. We examined the survival of subjects with AD and non-AD controls with respect to ApoE phenotype and gender in a population-based longitudinal study. Cognitive evaluation was performed for a total of 980 subjects (then aged 69-78 years), and 48 cases with AD were identified. ApoE4 phenotype was more frequently present among subjects with AD. In the whole study population, survival was not related to the presence of AD or ApoE4 phenotype. Risk of death was increased for men compared to women, independently of the ApoE4 phenotype (HR 0.5, 95% confidence interval 0.44-0.69). In subjects with AD, the presence of ApoE4 alone did not influence survival. However, in the AD group, ApoE4-negative men had significantly increased risk of mortality compared to the risk in ApoE4-negative women (p < 0.01). We conclude that the presence of ApoE4 phenotype or AD did not influence mortality in the aged population. Once AD had become manifest, ApoE4 alone did not relate to survival. However, in subjects with AD not carrying ApoE4, men had reduced survival compared to women.

Aged↗
PubMedDate not supplied

Effect of cholecystectomy on plasma lipid and lipoprotein levels.

BACKGROUND/AIM: This study was designed to elucidate the effect of cholecystectomy, a common surgical procedure, on the concentrations of plasma lipids and lipoproteins. PATIENTS AND METHODS: 19 consecutive patient with symptomatic gallstone disease and emptying gallbladder, and 16 control patients (Nissen-Rosetti fundoplication) were studied. Cholesterol, triglyceride, and protein concentrations of various lipoproteins were analysed. RESULTS: Plasma total and LDL cholesterol levels were significantly reduced in cholecystectomy patients (p = 0.0048 and p=0.0239) at day 3 after the operation, the values returning to the preoperative level thereafter. In the control patients similar trends were observed for total and LDL cholesterol levels but these changes did not reach statistical significance. In cholecystectomy patients a significant increase was noticed in the very-low-density lipoprotein and intermediate density lipoprotein apoprotein B concentration three years after surgery (p= 0.0019 and p=0.0001). CONCLUSIONS: These minor changes in plasma lipoproteins following cholecystectomy are unlikely to have any importance in the development coronary heart disease. They indicate, however, altered enterohepatic metabolism of cholesterol after the removal of the gallbladder.

Adult↗