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Biomedical subjects

J Norseth

Publications and source records attributed to J Norseth.

At least 19 recordsLinked to original sources

Zinc deficiency is of limited clinical importance in the elderly (>69 y) of Oslo.

BACKGROUND: Zinc is an important trace element, and deficiency can cause disease and impairment of several physiological functions. OBJECTIVE: To examine s-zinc concentration in a large elderly population (347 subjects), and correlate it to standard biochemical markers, nutritional core indicators, and anamnestic data. DESIGN: A randomized population survey, studying two groups of elderly; one living at home and the other recently admitted to hospital. RESULTS: Serum zinc concentration was (Mean SD) in the home group (11.6 1.8 micromoles /L), and in the hospital group (11,5 2.5 micromoles /L). S-zinc was below 8 micromol/L in the hospital group in 22 of 250 patients and in 4 out of 97 of the home group. There was no significant difference in prevalence of zinc deficiency in hospital versus the home living group. Low s-zinc was significantly correlated to diarrhea, but to no other marker used in this study. CONCLUSION: Zinc deficiency is most probably of limited clinical importance in the elderly of Oslo, and there is no biochemical or nutritional marker that in addition to s-zinc can aid in the diagnosis.

Aged↗

The magnesium loading test: reference values in healthy subjects.

The magnesium loading test is a useful tool in the diagnosis of magnesium deficiency. In order to establish a reference range in normal subjects, 88 healthy men and women aged between 18 and 66 years were given 30 mmol magnesium intravenously during eight hours as a loading test, urine was collected from start of infusion for 24 h for measurement of magnesium excretion. The magnesium mean retention was 6.3 +/- 10.3% of the loading dose, and the 0.025 and 0.975 fractiles were -19.5% and 27.5%, respectively. There was no significant difference between the sexes or in the different age groups studied. There was no correlation between the magnesium retention and serum magnesium or with basal urinary magnesium excretion. An excess excretion of magnesium was observed the postload day compared to baseline, but the excretion 24 and 48 h after the magnesium loading were closely correlated, suggesting that 24 h urinary sampling is sufficient. In order to examine the reproducibility of the test 23 of the subjects underwent two magnesium loading tests 4 weeks apart. The mean difference between two repeat magnesium loading tests was 2.0% with a SD of 8.1% and a 95% confidence interval of -1.6-5.5%. Normal saline did not affect baseline magnesium excretion. Concomitant administration of ethanol or physical exercise caused greater variation in magnesium excretion, whereas furosemide was without effect. The 8 h magnesium loading test with 24 h urine sampling seems to be fairly reproducible, is adequate for clinical use, but the normal range is wide.

Adolescent↗

[Familial hypercholesterolemia--intensive diet therapy combined with drug therapy].

The aim of the investigation was twofold: to study the effect of lovastatin, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, alone and in combination with other lipid lowering drugs in an open 48 week single centre study, and to study if lipid lowering drugs influence adherence to diet in adult patients with familial hypercholesterolemia. Lovastatin monotherapy (80 mg daily) for 12 weeks reduced serum cholesterol, LDL-cholesterol and triglycerides levels by 36%, 44% and 24% respectively. HDL-cholesterol level was increased by 12%. The addition of 16 g cholestyramine daily further increased the reduction of total cholesterol and LDL-cholesterol levels by 17% and 24% respectively. Addition of 1 g probucol daily decreased total cholesterol, LDL-cholesterol and HDL-cholesterol levels by 9%, 5% and 27% respectively. Addition of omega-3-fatty acids (3.6 g daily) reduced total cholesterol, LDL-cholesterol and triglycerides levels by 10%, 12% and 20% respectively. Administration of potent lipid lowering agents did not influence adherence to a diet with a mean daily fat energy of 21% (CI: 20-22), cholesterol of 177 mg (CI: 157-196) and P/S ratio of 0.75 (CI: 0.66-0.84). A significant increase in liver enzymes was recorded in only one patient. One patient was withdrawn from the study because of myositis.

Adolescent↗

Short-term effects of treatment with simvastatin on testicular function in patients with heterozygous familial hypercholesterolaemia.

The effects of simvastatin 40 mg per day for 14 weeks on the pituitary-testis axis of 19 men with familial hypercholesterolaemia have been examined in a single-blind study. Simvastatin significantly reduced serum low density lipoprotein (LDL) cholesterol and triglycerides by 45% and 30%, respectively, and significantly increased high density lipoprotein (HDL) cholesterol by 15%. The alterations, which were stable 4 weeks after the start of treatment, were not associated with any significant change in sperm quality, the seminal plasma concentrations of various sex gland products (prostate-specific acid phosphatase, polyamines, citrate, fructose, alpha-glucosidase), or the serum concentrations of cortisol, testosterone, LH, FSH, or prolactin. It is concluded that a short-term reduction in circulating LDL-cholesterol has no marked effect on testicular function or sperm quality.

Adult↗

Clinical and biochemical heterogeneity in conditions with phytanic acid accumulation.

Phytanic acid accumulation has for more than 20 years been used as a diagnostic criterion of Refsum's disease. Recently, however, phytanic acid has also been found in peroxisomal disorders (Zellweger's syndrome, neonatal adrenoleukodystrophy, infantile Refsum's syndrome, rhizomelic chondrodysplasia punctata). The 17 patients with Refsum's disease in the present study had serum phytanic acid values differing from 73 to less than 0.5 mg/dl (normal). alpha-Oxidation of phytanic acid in skin fibroblast cultures showed a defective capacity in all, with only small differences in residual activity. Phytanic acid determinations in serum from 3 of the 7 patients with peroxisomal disorders showed slightly elevated levels in 2. The alpha-oxidation capacity in the fibroblasts was defective in all, with a residual activity similar to that of Refsum's disease. An assay of the alpha-oxidation capacity may be useful in the diagnosis of both Refsum's disease and the peroxisomal disorders. The distinction between Refsum's disease and the peroxisomal disorders can easily be done on a clinical basis.

Adrenoleukodystrophy↗

Phytanic acid oxidase activity in cultured skin fibroblasts. Diagnostic usefulness and limitations.

Patients with Refsum's disease lack the ability to degrade phytanic acid to pristanic acid and CO2. This defect is expressed in fibroblasts from the patients. An assay system for the degradation of phytanic acid in cultured skin fibroblasts is described. The assay makes it possible to single out patients with Refsum's disease from the cob-web of clinically related conditions. The sensitivity is, however, not good enough to diagnose the heterozygous state. A defect of the same pronounced degree as in Refsum's disease is also found in fibroblasts from patients with Zellweger's syndrome, neonatal adrenoleukodystrophy, and infantile Refsum's disease. The radioactive material remaining in the cells after incubation was identified as unmetabolized phytanic acid. No traces of radioactive intermediates could be found in the cells from any of the patient groups. This might indicate that the defects both in Refsum's disease and in the peroxisomal disorders are located either at the same metabolic step or at steps which are closely linked to each other.

Carbon Dioxide↗

Transcapillary colloid osmotic gradient, plasma volume and interstitial fluid volume in long-term type 1 (insulin-dependent) diabetes.

Plasma and subcutaneous colloid osmotic pressure, transcapillary escape rate of albumin, plasma volume and extracellular fluid volume were measured in 10 long-term Type 1 (insulin-dependent) diabetic patients without clinical nephropathy. Interstitial colloid osmotic pressure was reduced compared with normal subjects (12.9 +/- 3.0 versus 15.8 +/- 2.7 mmHg, p less than 0.05) and the transcapillary colloid osmotic gradient increased (17.0 +/- 2.4 versus 12.8 +/- 2.7 mmHg, p less than 0.01). Plasma volume was in the normal range and interstitial fluid volume increased by approximately 21% compared with normal subjects (p less than 0.01). Transcapillary escape rate of albumin was significantly increased compared with normal subjects (8.9 +/- 1.9 versus 5.1 +/- 1.6% h, p less than 0.01). A negative correlation was found between the transcapillary colloid osmotic gradient and interstitial fluid volume (r = 0.6, 0.01 less than p less than 0.05). These results suggest that the increased small vessel permeability in long-term diabetes leads to wash-out of interstitial proteins and the resulting increased transcapillary colloid osmotic gradient tends to preserve the plasma volume and to limit the tendency to increased interstitial fluid volume.

Adult↗

Long-term effects of high-fat diets on peroxisomal beta-oxidation in male and female rats.

In weanling male rats a 4-fold increase of heart triacylglycerols was observed after three days on a high-fat diet containing partially hydrogenated fish oil (PHFO). In female rats this increase was only about 50%. No significant differences were observed between female and male rats in the fatty acid composition of the accumulated lipids. The initial level of peroxisomal beta-oxidation activity was similar in male and female rats in both liver and heart. After three weeks of receiving high-fat diets, the rats showed a marked increase in peroxisomal beta-oxidation activity with PHFO in the diet and less with soybean oil (SO), confirming previous studies with male rats. Catalase activity was similarly affected in hearts of both sexes. In male rats the levels of peroxisomal beta-oxidation observed after three weeks of feeding on the high-fat diets were found to be maintained, both in liver and heart, during a feeding period of three months. The response to high-fat diets in females, however, seems to be further accentuated after three months of feeding, resulting in a capacity of peroxisomal beta-oxidation in liver of about three times that of the male rats when calculated on a total body-weight basis.

Animals↗

An evaluation of ultrafiltration as treatment of diuretic-resistant oedema in nephrotic syndrome.

Plasma volume, plasma colloid osmotic pressure, creatinine clearance and sodium excretion were measured before and after ultrafiltration treatment in six patients with diuretic-resistant nephrotic syndrome. The mean total ultrafiltrate volume in two sessions on two successive days was 7460 ml, the mean ultrafiltration rate was 22.0 ml/min and the calculated plasma refilling rate was 19.9 ml/min. Plasma volume and creatinine clearance were unchanged and sodium excretion was reduced after treatment. A short-lasting drop in blood pressure was seen in 3 of the 12 treatment sessions. No other complications were noted. Ultrafiltration is a safe and useful alternative in the treatment of the few patients with massive oedema due to nephrotic syndrome not responding to conventional therapy.

Blood↗

Interstitial fluid volume, plasma volume and colloid osmotic pressure in patients with nephrotic syndrome.

Colloid osmotic pressure in plasma (IIp) and in subcutaneous interstitial fluid (IIi) (wick technique), plasma volume (PV) and interstitial fluid volume (IFV) were measured in nephrotic patients (n = 11) and in healthy controls. Six of the patients were treated with ultrafiltration and the parameters were measured before and after withdrawal of mean 7460 ml (total ultrafiltrate in two sessions). In the nephrotic patients mean IIp was 11.6 mmHg and IIi was 3.9 mmHg compared to 28.6 mmHg and 15.8 mmHg, respectively, in healthy controls. PV was in the normal-to-high range and IFV was increased to 150% of the valued in controls. No statistically significant change in PV, IIp or IIi was found after ultrafiltration, and IFV was reduced by 20%. The results indicate that reduction in IIi is an important oedema-preventing factor and that the reduction in interstitial protein mass is more than proportional compared to the degree of hypoproteinaemia. Ultrafiltration in the rate and magnitude we have used, leads to reduction in IFV, but small changes in PV, IIp or IIi.

Adult↗

Acyl-CoA synthetase activity of rat heart mitochondria. Substrate specificity with special reference to very-long-chain and isomeric fatty acids.

The acyl-CoA synthetase (acid: CoA ligase (AMP-forming), EC 6.2.1.3) activity of rat heart has been measured in fatty acid-depleted fractions of mitochondria, microperoxisomes and microsomes. The assay was based on (i) the measurement of the reaction product AMP by high-performance liquid chromatography or (ii) a coupled reaction in which the intramitochondrial (matrix) CoASH is the final acyl acceptor and the redox state of the flavoproteins in the acyl-CoA dehydrogenase pathway is used to determine the intramitochondrial level of acyl-CoA. This spectrophotometric method was also used to estimate the 'outer' carnitine long-chain acyltransferase (palmitoyl-CoA:L-carnitine O-palmitoyltransferase, EC 2.3.1.21) activity. Comparison of the distribution of long-chain acyl-CoA synthetase activity and marker enzymes in the various subcellular fractions revealed that the synthetase activity is exclusively localized in the mitochondrial fraction. Experimental evidence is presented in support of the conclusion that the chain-length specificity of saturated and monounsaturated fatty acids (16:1-22:1) for the acyl-CoA synthetase is mainly determined by the availability of the fatty acid at the active site, which is largely determined by the affinity of binding of fatty acids to the bulk phase of the mitochondrial phospholipids. Among the 22:1 isomers, 22:1(11) (cis) (cetoleic acid) revealed a slightly higher activity (1.4-fold) than 22:1(13) (cis) (erucic acid). The polyunsaturated fatty acids tested were rather poor substrates. Using isolated intact mitochondria and 16:0 or 22:1(13) (cis) as the substrates, it was found that the initial rate of the 'outer' long-chain acyltransferase activity was approximately four times higher than that of the long-chain acyl-CoA synthetase. The data support the hypothesis that the long-chain acyl-CoA synthetase reaction is rate-limiting in the sequence of coupled reactions leading to beta-oxidation in the mitochondrial matrix.

Animals↗

Stimulation of microperoxisomal beta-oxidation in rat heart by high-fat diets.

1. Heart microperoxisomal beta-oxidation activity, measured as cyanide-insensitive palmitoyl-CoA-dependent NAD+-reduction, was detected in a microperoxisome-enriched fraction from rat myocardium. The effect on this microperoxisomal beta-oxidation of the fatty acid composition of the dietary oils was investigated. 2. Feeding 15% (w/w) high erucic acid rapeseed oil or partially hydrogenated marine oil for 3 weeks increased the microperoxisomal beta-oxidation in the heart 4-5-fold, compared to a soybean oil diet. Increasing amounts (5-30%, w/w) of partially hydrogenated marine oil in the diet led to a 3-fold increase in the microperoxisomal beta-oxidation capacity at 20% or more of this oil in the diet. 3. The activity of the microperoxisomal marker enzyme catalase followed closely the cyanide-insensitive palmitoyl-CoA-dependent NAD+-reduction, except when feeding more than 20% (w/w) partially hydrogenated marine oil where a significant decrease in the catalase activity was observed. 4. In rapeseed oil-fed animals the extent of increase of microperoxisomal beta-oxidation was directly correlated to the amount of erucic acid (22:1, n-9 cis) in the diet. 5. Feeding partially hydrogenated rapeseed oil or partially hydrogenated soybean oil resulted in activities of microperoxisomal beta-oxidation significantly lower than in the corresponding unhydrogenated oils. No significant difference could be detected between diets containing hydrogenated or unhydrogenated marine oil. 6. Addition of 5% soybean oil to the essential fatty acid-deficient, partially hydrogenated marine oil diet did not change the effect on the microperoxisomal beta-oxidation activity. 7. Clofibrate feeding increased the heart microperoxisomal beta-oxidation capacity 2.5-fold, as compared to a standard pelleted diet. 8. These findings are discussed in relation to the transient nature of the cardiac lipidosis observed with animals fed on diets rich in C22:1 fatty acids. It is concluded that the heart plays an important part in the adaptation process.

Animals↗

Metabolism of erucic acid in adipocytes isolated from rat epididymal fat.

The metabolism of [14-14C]erucic acid and [U-14C]palmitic acid has been investigated in adipocytes isolated from rat epididymal fat. The rate of acylation of [14C]erucic acid in cellular lipids and oxidation to CO2 and acid-soluble activity was ca. 1/3 of the rate with [14C]palmitic acid as substrate. A maximal incorporation of fatty acids in triacylglycerol was found at a fatty acid concentration of 0.8 mM in the medium, both with [14C]erucic acid and [14C]palmitic acid as substrate. Glucose added to the medium increased the esterification and decreased the oxidation of both fatty acids. No significant chain-shortening of [14C]erucic acid to shorter monoenes was identified in the fat cells. Increasing concentrations of unlabeled palmitic acid in the incubation medium markedly inhibited the esterification of [14C]erucic acid, whereas unlabeled erucic acid had little effect on the rate of esterification of [14C]palmitic acid.

Adipose Tissue↗

Hydrodynamic parameters and isolation of mitochondria, microperoxisomes and microsomes of rat heart.

1. Analytical differential centrifugation of rat heart homogenates revealed a single population of mitochondria and microperoxisomes. Using cytochrome c oxidase, malate dehydrogenase and amine oxidase as mitochondrial marker enzymes, the s-value of mitochondria was estimated to s = 10326 +/- 406 S (average for the three marker enzymes). The s-value of microperoxisomes was found to be s = 1381 +/- 40 S using catalase as the marker enzyme. The s-value for the two organelles did not change significantly when the isoosmotic sucrose medium was substituted by an isoosmotic mannitol medium. 2. Analytical differential centrifugation revealed a polydispercity of the microsomal fraction using glucose-6-phosphatase and NADPH-cytochrome c reductase as the marker enzymes. The s-values were found to be sH1 = 1569 +/- 412 S (NADPH-cytochrome c reductase), sH2 = 1195 +/- 400 S (glucose-6-phosphatase) and sL = 153 +/- 28 S (NADPH-cytochrome c reductase and glucose-6-phosphatase). The recovery of marker enzymes in the isolated subcellular fractions was in the range of 84-94%. 3. When the mitochondrial and microperoxisomal fractions were subjected to isopycnic gradient centrifugation, using a self-generating gradient of polyvinylpyrrolidone-coated colloidal silica particles (Percoll) in 0.25 M sucrose medium, buoyant densities of 1.10 g/cm3 (main fraction of mitochondria) and 1.06 g/cm3 (main fraction of microperoxisomes) were obtained. The density gradient centrifugation separated microperoxisomes from contaminating lysosomes of high specific activity in acid phosphatase. A value 1.04 g/cm3 was found for the density of the microsomal fraction. 4. Based on the estimated s-values, an optimal procedure is described for the isolation of mitochondrial and microperoxisomal fractions from rat heart muscle.

Animals↗

Studies on the regulation of arachidonic acid synthesis in isolated rat liver cells.

Isolated liver cells from rats fed a diet deficient in essential fatty acids were used to study the oxidation, esterification and, especially, the desaturation and chain elongation of [1-14C]linoleic acid. 14C-labelled arachidonic acid (20:4) and smaller amounts of eicosatrienoic acid (20:3) were recovered mainly in the phospholipids, while gamma-linolenic acid (18:3) was found in both the phospholipids and the triacylglycerol fraction. Lactate strongly increased the formation of arachidonic acid, which was found mainly in the phosphatidylcholine and the phosphatidylinositol fractions. Lactate reduced the amounts of gamma-linolenic acid. Glucagon and (+)-decanoylcarnitine reduced the formation of arachidonic acid, and (+)-decanoylcarnitine increased the incorporation of gamma-linolenic acid especially, in the triacylglycerol fraction. Increasing concentrations of the [1-14C]linoleic acid substrate increased the formation of arachidonic acid and of the other chain-elongated or desaturated fatty acids. Lactate also stimulated the formation of arachidonic acid in liver cells from animals fed adequate amounts of essential fatty acids. It is suggested that dietary and hormonal factors which can change the intracellular levels of malonyl-CoA may influence both the ratio of arachidonic acid/gamma-linolenic acid formed and the total amounts of desaturated and chain-elongated fatty acids formed from linoleic acid.

Animals↗

Increased beta-oxidation of erucic acid in perfused hearts from rats fed clofibrate.

1. The metabolism of [14-14C]erucate and [U-14C]palmitate has been investigated in perfused heart from rats fed 0.3% clofibrate for 10 days and from control rats. 2. The total uptake of fatty acids in the heart increased in the clofibrate fed group. Clofibrate increased the oxidation of [14-14C]erucic acid by 100% and the oxidation of [U-14C]palmitic acid by 30% compared to controls. 3. The chain-shortening of erucate to C20:1 and C18:1 fatty acids in the perfused heart was stimulated at least two-fold by clofibrate feeding. 4. The activity of the peroxisomal marker enzyme catalase increased 60%, the activity of cytochrome oxidase increased approx. 16% and the content of total coenzyme A increased 30% in heart homogenates from rats fed clofibrate compared to controls. 5. The isolated mitochondrial fraction from clofibrate fed rats showed an increased capacity for oxidation of palmitoylcarnitine and decanoylcarnitine, while the oxidation of erucoylcarnitine showed little change. 6. It is suggested that clofibrate increases the oxidation of [14-14C]erucic acid in the perfused heart by increasing the capacity for chain-shortening of [14-14C]erucate in the peroxisomal beta-oxidation system.

Animals↗

The effect of feeding rats with partially hydrogenated marine oil or rapeseed oil on the chain shortening of erucic acid in perfused heart.

1. The metabolism of [14(-14)C]erucic acid and [U-14C]palmitic acid was studied in perfused hearts from rats fed diets containing hydrogenated marine oil, rapeseed oil or peanut oil for three weeks. 2. [14C]Erucic acid was shortened to [14C]eicosenoic acid (20 : 1, n -- 9) and [14C]oleic acid (18 : 1, n -- 9) in perfused rat hearts from all diet groups. The rapeseed oil diet caused a three-fold increase and the marine oil diet a four-fold increase in the amount of chain-shortened products recovered in heart lipids at the end of perfusion, compared to peanut oil diet. 3. The content of C16:1, C18:1 and C20:1 fatty acids was increased in heart lipids of rats fed hydrogenated marine oil or rapseed oil diet, compared to peanut oil diet. 4. Feeding hydrogenated marine oil or rapeseed oil to the rats induced a 85% increase in catalase activity, a 20% increase in the activity of cytochrome oxidase and a 30--40% increase in the content of total CoA in the heart compared to rats fed peanut oil diet. 5. It is suggested that [14(-14)C]erucic acid is shortened by the beta-oxidation system of peroxisomes in the heart. The increased chain shortening in the hearts from animals fed rapeseed oil or partially hydrogenated marine oil for three weeks may be an important part of an adaptation process.

Animals↗