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Biomedical subjects

L Berglund

Publications and source records attributed to L Berglund.

At least 163 records · Page 9Linked to original sources
PubMed1994

Treatment of IgA nephropathy with omega-3-polyunsaturated fatty acids: a prospective, double-blind, randomized study.

In several studies diets supplemented with fish oil containing a high proportion of omega-3-polyunsaturated fatty acids (w-3-PUFA) have been shown to produce beneficial effects, such as a reduction in blood pressure, lipid levels and inflammation, all of which may affect the course of IgA nephropathy. However, the results of hitherto published studies concerning IgA nephropathy have been inconclusive. We therefore carried out a prospective, randomized, placebo-controlled six-month study with a higher daily dose of w-3-PUFA than used in previous studies. Thirty-two adult patients with biopsy-proven IgA nephropathy and proteinuria completed the study: 15 were assigned to a fish-oil product with a high percentage of w-3-PUFA (K 85, with 55% eicosapentenoic and 30% docosahexenoic acid) and 17 to corn oil, 6g daily of either oil. At the start, no significant differences were found between the two groups (K85: 3 females/12 males, mean age 39 years (range 22-64), corn oil: 4 females/13 males, age 42 years (range 26-68). By six months, supplements of K85 resulted in a slight but significant reduction in glomerular filtration rate (GFR) compared to the start: 51Cr-EDTA: 63 +/- 22 to 59 +/- 21 ml/min/1.73 m2 (p < 0.05), creatinine clearance: 91 +/- 31 to 79 +/- 25 ml/min (p < 0.01), s-creatinine: 131 +/- 39 to 139 +/- 39 mumol/l, whereas no change in GFR was observed in the corn oil group. The urinary total protein and red blood cell excretions were not affected in any of the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Pravastatin and gemfibrozil alone and in combination for the treatment of hypercholesterolemia.

PURPOSE: To compare the efficacy and safety of pravastatin, gemfibrozil, combined therapy, and placebo in the treatment of hypercholesterolemia. PATIENTS AND METHODS: At 5 centers in Sweden and 2 in Finland, 290 ambulatory patients were randomized to active treatment or placebo for 12 weeks following a single-blind placebo lead-in period. The study was double-blind and placebo-controlled. Patients has plasma total cholesterol levels of at least 6.0 mmol/L or in the 90th percentile by age and sex and triglycerides less than 4.0 mmol/L. Concentrations of lipids, lipoproteins, and apolipoproteins were measured, and clinical laboratory tests included liver function and creatine kinase determinations. RESULTS: Pravastatin reduced total cholesterol (26.3% versus 15.2%, p < or = 0.01), low-density lipoprotein cholesterol (LDL-C) (33.5% versus 16.8%, p < or = 0.01), and apolipoprotein B (28.8% versus 15.3%, p < or = 0.01) more than gemfibrozil. Gemfibrozil reduced very-low-density lipoprotein cholesterol (VLDL-C) (49.1% versus 21.9%, p < or = 0.01) and triglycerides (42.2% versus 14.2%, p < or = 0.01) and increased high-density lipoprotein cholesterol (HDL-C) (15.2% versus 5.9%, p < or = 0.01) more than pravastatin. Pravastatin and gemfibrozil increased apolipoprotein A-I comparably (3.3% versus 5.0%, p = NS). The combination significantly (p < or = 0.01) reduced total cholesterol (29.0%), LDL-C (37.1%), VLDL-C (49.4%), and apolipoprotein B (31.6%), and increased HDL-C (16.8%). The combination reduced the total cholesterol/HDL-C (39.3%) and LDL-C/HDL-C (45.8%) ratios significantly (p < 0.01). Adverse events and clinical laboratory abnormalities were generally mild and transient in all groups, although creatine kinase tended to be higher with combination therapy. Study drugs were withdrawn from two patients with asymptomatic creatine kinase elevations. Severe myopathy was not observed; however, the presence of subclinical musculoskeletal effects cannot be excluded. CONCLUSIONS: Co-administration of pravastatin and gemfibrozil combined the specific effects of the two drugs on lipoprotein concentrations and ratios. The incidence of side effects was low; severe myopathy did not occur. The combination may be useful in selected cases of combined hyperlipidemia; however, since myopathy at a low incidence or after long-term therapy cannot be excluded, the routine use of combination therapy is not advisable.

Adult↗
PubMed1993

Lipoprotein(a) in nephrotic syndrome.

Lipoprotein(a) [LP(a)] is an independent risk factor for cardiovascular disease, and it has also been speculated that it promotes thrombosis. Recent studies have shown that patients with gross proteinuria have greatly increased plasma levels of Lp(a), but the genesis is obscure. In the present study, plasma Lp(a) levels were measured in 31 patients with nephrotic syndrome (NS), 24 patients with IgA nephropathy and 43 healthy control subjects. Lp(a) levels were significantly elevated in NS (median 49.0 mg/dl), in contrast to the control subjects and patients with IgA nephropathy (median 7.0 and 9.7 mg/dl, respectively). Plasma Lp(a) levels fell markedly in 10 of 10 NS patients after remission. In NS, Lp(a) levels correlated directly with serum cholesterol levels (P < 0.05) and indirectly with plasma orosomucoid levels (P < 0.05), but not with serum albumin, triglycerides, HDL cholesterol, urinary protein excretion or GFR. In addition, Lp(a) tended to be higher in NS patients with edema (median 54.3 mg/dl) than in patients without edema (19.0 mg/dl; P = 0.06). Nine NS patients were further evaluated with plasma ANP levels and urinary sodium excretion. Plasma Lp(a) correlated directly with ANP (P < 0.01) and indirectly with urinary sodium excretion (P < 0.05). Excellent correlations were found between Lp(a) and VLDL cholesterol and VLDL triglycerides, respectively, suggesting a close link between Lp(a) and triglyceride-rich lipoproteins in nephrosis.

Adrenal Cortex Hormones↗
PubMed1993

Studies on triglyceride metabolism: phosphatidate phosphohydrolase from guinea pig harderian gland.

The guinea pig Harderian gland, located in the orbit, is characterized by a high production of lipids. However, little is known about the regulation of the metabolic pathways involved. In the present paper the properties of guinea pig Harderian gland phosphatidate phosphohydrolase, a key enzyme in triglyceride biosynthesis, was investigated. The enzyme was present both in the cytosolic and the microsomal fraction from the gland. Cytosolic phosphatidate phosphohydrolase was purified by hydroxylapatite chromatography. The enzyme was dependent on magnesium ions and inhibited in the presence of fluoride. The dependence on the substrate phosphatidate was investigated and the apparent Km for phosphatidate was about 0.6 mM. Phosphatidate phosphohydrolase activity was influenced by different phospholipids. As is the case for the rat liver enzyme, phosphatidylethanolamine was found to stimulate the enzyme activity. The results indicate that Harderian gland phosphatidate phosphohydrolase has similar properties as the corresponding enzyme from rat liver, suggesting that it may be of regulatory importance.

Animals↗
PubMed1993

Non-steady-state kinetics of low density lipoproteins in man: studies after plasma exchange in healthy subjects and patients with familial hypercholesterolaemia.

Five patients with heterozygous familial hypercholesterolaemia (FH), one patient with non-familial hypercholesterolaemia, and four healthy normals were treated with plasma exchange (PE). In order to achieve a non-steady-state situation with low plasma cholesterol levels, PE was performed twice in each subject at an interval of 1-3 days. At each time, 1500 ml of plasma were removed and replaced with colloids and albumin. Lipoprotein analyses were performed daily in all subjects for a period of 14 days following PE. Kinetic calculation of LDL cholesterol data using a two-compartment open model was performed, and rate constants, synthetic rate and apparent clearance of LDL were determined. A lower clearance and a tendency towards a higher synthesis of LDL were observed in the FH patients. In four of the subjects, LDL kinetics was also studied with the conventional 125I-LDL turnover technique. The synthetic rates of LDL were compared using data derived from PE and 125I-LDL kinetics. The two techniques showed a good correlation (r = +0.93) although synthetic rates in general were higher when calculated from the 125I-LDL procedure (3.98 vs. 2.64 mmol d-1 for LDL cholesterol synthesis). The results indicate that non-steady-state kinetics of LDL, as measured using the PE technique, is a useful method for analysis of LDL metabolism.

Adult↗
PubMed1993

Apolipoprotein E phenotypes in familial hypercholesterolaemia: importance for expression of disease and response to therapy.

To study the possible importance of variation at the apolipoprotein (apo) E gene locus for the clinical expression of heterozygous familial hypercholesterolaemia (FH), we determined apo E phenotype and serum lipoprotein pattern in 120 patients with FH. The allele frequency of the patients studies were: epsilon 2 0.033, epsilon 3 0.733, and epsilon 4 0.233. There was no influence of apo E phenotype on the serum concentrations of total. VLDL, LDL or HDL cholesterol, triglycerides, or of apo AI, B or (a). Serum concentrations of apo E were significantly higher in patients with the apo E 3/3 phenotype compared to those with apo E 4/3 or 4/4, and the highest concentrations were found in patients carrying the epsilon 2-allele. The cholesterol-lowering response to therapy with cholestyramine or pravastatin was not related to apo E phenotype. It is concluded that variation at the apo E gene locus is not of major importance for the expression of heterozygous FH.

Apolipoproteins E↗
PubMed1993

Effect of 3-thiadicarboxylic acid on lipid metabolism in experimental nephrosis.

The effect of the sulfur-substituted fatty acid analogue 1,10 bis(carboxymethylthio)decane, also known as 3-thiadicarboxylic acid, on puromycin aminonucleoside-induced nephrotic hyperlipidemia was studied in rats. Treatment with 3-thiadicarboxylic acid (250 mg/kg) for 5 days reduced plasma levels of triglycerides from 5.8 to 2.7 mmol/L and cholesterol from 11.0 to 7.7 mmol/L. This was accounted for by decreases in very-low-density lipoprotein triglycerides, very-low-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, without any major changes in the composition of plasma lipoproteins. The activities of two enzymes involved in fatty acid synthesis (ATP:citrate lyase and fatty acid synthetase) were inhibited by 3-thiadicarboxylic acid treatment, whereas acetyl-coenzyme A carboxylase activity was unchanged. In contrast, treatment with the sulfur-substituted fatty acid analogue induced the peroxisomal beta-oxidation of fatty acids ninefold and the mitochondrial beta-oxidation by 54% to 73%, depending on the substrate used. This was accompanied by a 26% reduction in hepatic triglyceride secretion rate. The hepatic phosphatidate phosphohydrolase activity was unchanged. 3-Thiadicarboxylic acid treatment suppressed the activity of the rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, by 58%, whereas hepatic LDL receptor expression was unaltered. The activities of lipoprotein lipase and hepatic lipase were unchanged by treatment. These results demonstrated that treatment with 3-thiadicarboxylic acid ameliorates hyperlipidemia in experimental nephrosis primarily by decreasing the overproduction of very-low-density lipoprotein present. The data also indicate that hepatic very-low-density lipoprotein synthesis and secretion is strongly influenced by the availability of the fatty acid substrate under the same hyperlipidemic conditions.

ATP Citrate (pro-S)-Lyase↗
PubMed1993

Antioxidant treatment inhibits the development of intimal thickening after balloon injury of the aorta in hypercholesterolemic rabbits.

The effect of the antioxidant butylated hydroxytoluene (BHT) on the accumulation of intimal smooth muscle cells (SMC) and development of intimal thickening after balloon catheter injury of the aorta were studied in rabbits with dietary-induced hyperlipidemia. Two sets of New Zealand White rabbits (eight rabbits in each group) were fed either 0.25% cholesterol or 0.25% cholesterol/1% BHT for a total of 6 wk. Serum lipid levels did not differ between the two groups. 3 wk after the start of the study, a balloon injury of the aorta was performed, after which the rabbits were kept on their respective diets for another 3 wk. After this period of time, the rabbits were killed and their aortas were investigated. The BHT-treated rabbits had only one fourth of the intimal thickness (P < 0.0001) and half the number of SMC/mm intima (P < 0.001), as compared to the rabbits fed only cholesterol. There was also a lower number of macrophages in the BHT-treated group. T lymphocytes were present in the intima of cholesterol-fed rabbits, whereas no such cells could be identified in the BHT-fed animals. There were significantly lower levels of autooxidation products of cholesterol (7-oxocholesterol, cholesterol-5,6-epoxide, and 7 beta-hydroxycholesterol) in the aortas of BHT-treated rabbits, P < 0.001. In conclusion, the antioxidant BHT effectively inhibited the accumulation of intimal SMC and the development of intimal thickening of the aorta in hypercholesterolemic rabbits after a balloon catheter-induced injury. These results indicate that antioxidants may modify intimal response to injury.

Actins↗
PubMed1993

Photodynamic properties of Sn-protoporphyrin: clinical investigations and phototesting in human subjects.

Pure synthetic metalloporphyrins have been developed for experimental and clinical use as inhibitors of heme oxygenase, the rate limiting enzyme in the catabolism of heme to bilirubin. Tin (Sn)-protoporphyrin is one such compound, which potently suppresses bilirubin production and thus jaundice in animals and man. We have previously reported that this metalloporphyrin in conjunction with UVA might be useful as a treatment for psoriasis. To assess the photodynamic properties of Sn-protoporphyrin, 31 subjects were investigated with regard to photosensitivity. In all subjects, phototesting using UVB, UVA, and visible light as well as photopatch testing was performed. Our investigations revealed that 16 of the 31 individuals treated with Sn-protoporphyrin developed a mild photosensitivity, mainly erythema of the hands and face, and in some cases a mild conjunctivitis. The duration of this sensitivity, which in no case caused discomfort, was dose-dependent and ranged from several weeks to 1-3 months. After administration of Sn-protoporphyrin, lower thresholds were found for both UVA and visible light, but the sensitivity for UVB was normal and photopatch tests were negative. In summary, the photosensitivity observed during Sn-protoporphyrin administration was of limited duration and magnitude and did not occur in all subjects. Thus, the combination of photoactive synthetic metalloporphyrins and artificial light might prove to be useful as a regimen for the treatment of skin disease.

Adult↗
PubMed1993

Measurement of friction between pulley and flexor tendon.

When tendon excursion takes place through the pulley, friction and drag are encountered at the interface. Repetitive exposure to such friction and attrition of the tendon has been considered one of the important factors causing cumulative trauma and leading to disorders such as tendinitis and tenosynovitis. In this study, development of an experimental method to evaluate friction and drag between the pulley and tendon under different loading conditions and joint configurations is considered. Verification of the model under an ideal situation of sutures across a mechanical pulley was performed.

Biomechanical Phenomena↗
PubMed1993

On the mechanism of the hypolipidemic effect of sulfur-substituted hexadecanedioic acid (3-thiadicarboxylic acid) in normolipidemic rats.

The mechanism behind the hypolipidemic effect of the sulfur-substituted non-beta-oxidizable fatty acid analogue 1,10 bis(carboxymethylthio)decane, also known as 3-thiadicarboxylic acid, was studied in normolipidemic rats. Treatment with 3-thiadicarboxylic acid markedly decreased plasma levels of free fatty acids, triglycerides, and cholesterol. This was accompanied by a corresponding reduction in very low density lipoprotein (VLDL)-triglyceride and low density lipoprotein (LDL)-cholesterol levels (by 46% and 42%, respectively), whereas the decrease in high density lipoprotein (HDL)-cholesterol levels was less pronounced (16%). However, the composition of the various plasma lipoprotein fractions was essentially unchanged. Fatty acid oxidation in both mitochondria and peroxisomes was stimulated in parallel; the activities of ATP:citrate lyase and fatty acid synthase, two key enzymes in fatty acid synthesis, were inhibited. Hepatic triglyceride biosynthesis was retarded, as indicated by a decrease in the liver triglyceride content along with a 30% reduction of hepatic VLDL-triglyceride secretion. This was accompanied by a 50% inhibition of phosphatidate phosphohydrolase. The activities of plasma lipoprotein lipase as well as hepatic lipase were somewhat higher (18%) in treated animals, suggesting a slight increase in the clearance potential of triglyceride-rich lipoproteins. The cholesterol-lowering effect was accompanied by a considerable reduction (75%) in HMG-CoA reductase activity and a less pronounced inhibition of cholesterol 7 alpha-hydroxylase (52%), and acyl-CoA:cholesterol acyltransferase (25%) activities. The present data suggest that the hypotriglyceridemic and hypocholesterolemic properties of sulfur-substituted fatty acid analogues are primarily due to effects on triglyceride and cholesterol synthesis.

Animals↗
PubMed1993

Apolipoprotein E polymorphism in a healthy Swedish population: variation of allele frequency with age and relation to serum lipid concentrations.

We analyzed blood samples from 407 healthy Swedish individuals, 244 men and 163 women, ages 17 to 86 years, for apolipoprotein (apo) E isoforms and serum triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol. Parallel genotyping by means of polymerase chain reaction (PCR)-amplified DNA was performed in 200 subjects. Identical results were obtained by genotyping and phenotyping in 95% of all subjects analyzed. The apo E allelic frequencies were 7.8% for epsilon 2, 71.9% for epsilon 3, and 20.3% for epsilon 4. Compared with other Caucasian populations, the present population had a high relative allelic frequency of epsilon 4. The epsilon 4 frequency decreased with increasing age and was significantly lower in individuals > 60 years of age (14.7%). When controlling for age and sex, there were strong correlations between total serum and LDL cholesterol and the various epsilon alleles. The epsilon 4 and epsilon 3 alleles correlated positively with serum cholesterol and the epsilon 4 allele correlated positively with LDL cholesterol. In contrast, HDL cholesterol and serum triglycerides did not show any correlation to the allele types. Thus, the results demonstrate a considerable age variation of the epsilon allele frequency among healthy Swedes and an influence of apo E alleles on serum and LDL cholesterol concentrations.

Adolescent↗
PubMed1992

The gene structure of tetranectin, a plasminogen binding protein.

The gene for human tetranectin was isolated from a genomic library with a mixture of degenerate oligonucleotide probes. The gene is about 12 kbp and contains two intervening sequences. The gene encodes a protein of 202 amino acid residues, with a signal peptide of 21 amino acid residues, followed by the tetranectin sequence of 181 amino acid residues. Northern blot analysis revealed that tetranectin mRNA was present in all eight tissues tested with the highest concentration in lung. Southern blot analysis showed hybridization to two genes. Further investigations are needed to determine whether the genes are allelic or non-allelic.

Amino Acid Sequence↗
PubMed1992

Longitudinal study and cost-benefit analysis of the effect of early treatment of posterior cross-bites in the primary dentition.

The aim of this study was to follow longitudinally a cohort of preschool children regarding the prevalence of lateral cross-bites and the effect of treatments carried out. Two-hundred-and-twenty-four children were examined when they were 3-5 years old and re-examined at 13-15 years of age. Orthodontic treatment of lateral cross-bites was registered from annual dental records from the Public Dental Service. In the primary dentition, 23.3 per cent of the children showed lateral cross-bites, of whom 5.7 per cent showed a lateral edge-to-edge relation. Selective grinding was carried out in the Public Dental Service in 62 per cent of the cross-bite children. Correction was registered in 64 per cent of these cases. Nine (45 per cent) of the 20 children with untreated lateral deviation showed spontaneous correction. Of the 171 children without cross-bites in the primary dentition, 14 (8 per cent) developed cross-bites in the permanent dentition. Although the benefits of early treatment for the developing dentition are obvious for functional reasons, the effectiveness of grinding, the type of treatment and the timing can be discussed from a cost-benefit point of view.

Adolescent↗
PubMed1992

Metabolism of plasma low density lipoproteins in familial combined hyperlipidaemia: effect of acipimox therapy.

Ten male patients with familial combined hyperlipidaemia (FCHL) were studied with regard to LDL metabolism and composition. The FCHL patients had higher LDL levels than healthy controls (5.4 +/- 1.4 vs. 3.7 +/- 0.7 mmol l-1; P < 0.005) and a higher rate of production of the lipoprotein (15.8 +/- 3.1 mg kg-1 d-1 in FCHL vs. 13.1 +/- 1.8 mg kg-1 d-1 in the normals; P < 0.005). The fractional catabolic rate of LDL was low-normal in the FCHL patients, with a high level of interindividual variation. The actual individual LDL cholesterol level within the FCHL patient group appeared to be more closely associated with the LDL apoB FCR value than the rate of production of the particle. Analysis of the LDL particles from FCHL patients revealed a relative enrichment in triglycerides, while the cholesterol content of the lipoprotein was normal. Institution of acipimox therapy in 8 patients reversed the high rate of synthesis of LDL (15.2 +/- 3.5 mg kg-1 d-1) to a more normal level (13.9 +/- 4.0 mg kg-1 d-1; P = 0.08), while the FCR did not change significantly. In conclusion, patients with FCHL show an apparent overproduction of LDL apoB, while the actual degree of LDL elevation appears to be dependent on the clearance capacity of the lipoprotein, measured as LDL apoB FCR. The overproduction defect of LDL apoB can, at least in part, be managed by treatment with the nicotinic acid analogue acipimox.

Adult↗
PubMed1992

Hormonal regulation of serum Lp (a) levels. Opposite effects after estrogen treatment and orchidectomy in males with prostatic carcinoma.

Serum concentrations of lipoprotein (a) [Lp (a)] were determined in two groups of elderly males suffering from prostatic carcinoma, who were randomized to treatment with estrogen (n = 15) or orchidectomy (n = 16). Estrogen was given as oral ethinylestradiol, 150 micrograms daily, combined with intramuscular polyestradiol phosphate, 80 mg/mo. The baseline levels were similar in both groups, but 6 mo after initiation of therapy, serum Lp (a) levels were decreased approximately 50% in the estrogen-treated group (P less than 0.001) in contrast to a 20% increase (P less than 0.01) in the orchidectomized group. Concomitantly, LDL cholesterol decreased by 30% and HDL cholesterol increased by almost 60% in the estrogen-treated patients. There was no relationship between the change in LDL cholesterol and Lp (a) reduction. In conclusion, Lp (a) levels in males were found to drastically decrease upon estrogen treatment and to increase after orchidectomy, suggesting that sex hormones, and particularly estrogens, exert a regulatory role on the serum Lp (a) level in man.

Aged↗