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Biomedical subjects

G Cederblad

Publications and source records attributed to G Cederblad.

At least 55 records · Page 3Linked to original sources

Spectrophotometry of carnitine in biological fluids and tissue with a Cobas Bio centrifugal analyzer.

A spectrophotometric method for carnitine has been adapted to the Cobas Bio centrifugal analyzer. The addition of carnitine to a system containing carnitine acetyltransferase (EC 2.3.1.7) and acetyl-CoA gives rise to the formation of CoA. The system is coupled to 5,5'-dithiobis(2-nitrobenzoate) (DTNB). Assay response varied linearly with concentration of carnitine over a wide concentration range. The total CV was 5.5% for a carnitine concentration in serum of 58.0 mumol/L. Analytical recovery of carnitine added to a serum sample was 93%. No interference was found in icteric, not grossly hemolyzed, lipemic, or uremic sera. Comparison with a radioenzymatic method showed that results correlated well (r greater than 0.965) but the present method gave values proportionally greater by 10 to 25% for samples of plasma, dialysis fluid, urine, and muscle tissue. Advantages over the original spectrophotometric assays involving DTNB include low reagent costs, rapidity, simplicity, and reproducibility. However, this modification is not as sensitive and probably not as specific as the radioenzymatic methods.

Acetylcarnitine↗

Changes in nutritional assessment variables caused by total parenteral nutrition in anorexia nervosa.

Nutritional assessment variables were measured weekly in 10 young women with severe anorexia nervosa during treatment with total parenteral nutrition (TPN) for a 5 week period. Before the start of treatment the patients had lost 25-53% of their habitual weight, triceps skin fold (TSF) and arm muscle circumference (AMC) measurements were below the 5th percentile and all were anergic in the delayed hypersensitivity (DH) response. Plasma protein levels were normal except in fibronectin and prealbumin where levels below the reference interval was found in five patients. During TPN the body weight increased most likely due to rehydration and increase in lean body mass. Significant increases were seen in body weight weekly, but in TSF and AMC only after 4 and 3 weeks respectively. TSF and AMC were still below or at the 5th percentile after 5 weeks of TPN. DH response as well as fibronectin and prealbumin levels normalised in all patients. Despite only partial recovery in body cell mass the clinical picture had changed markedly so that the patients now were amenable to psychotherapy and had an adequate intake of food orally, enabling further nutritional therapy to be completed without parenteral support.

Journal Article↗

Carnitine in maternal and neonatal plasma.

Total plasma carnitine was analysed in 19 women, with uncomplicated pregnancies, who underwent elective caesarean section, and in their neonates. The women were given a balanced glucose (glucose group) or saline (saline group) infusion, group allocation being on a random basis. The carnitine levels in maternal or infant plasma did not differ between these two groups. At delivery, the mean maternal carnitine value, 17.4 +/- 1.25 mumol/l, was lower than the mean infant value, 25.9 mumol/l +/- 2.67 (mean +/- SE, p less than 0.005) and lower than the mean value in non-pregnant, fertile women, i.e. 40.9 +/- 1.22 mumol/l. The mean carnitine value in the unfed neonate had not changed when the infant was 4 hours old. A positive correlation was found between carnitine levels in maternal and infant plasma (p less than 0.01). At delivery, the levels of non-esterified fatty acids and 3-OH-butyrate in infant plasma were different in the two groups, but not at 4 hours of age. The results suggest that the maternal carnitine level is the most important factor governing plasma carnitine levels in the neonate.

3-Hydroxybutyric Acid↗

L-carnitine and haemodialysis: double blind study on muscle function and metabolism and peripheral nerve function.

Twenty-eight haemodialysis patients were randomized to L-carnitine, 2 g i.v. three times a week, and saline over a 6-week period. No obvious deficiency of carnitine was found in vastus lateralis with a median value of 12.9 mmol/kg dry weight; range 6.2-21.4. Female patients had lower total plasma carnitine compared to female controls, p less than 0.002, whereas no decrease was found in males. No relationship was found between muscle and total plasma carnitine. After carnitine administration the muscle carnitine level increased about 60%, p less than 0.01, and the total plasma carnitine level more than tenfold, whereas the initially high degree of acylation decreased, p less than 0.02. Maximum dynamic muscular strength was reduced with a mean value of 44% compared with healthy controls. Total metabolic activity of isolated skeletal muscle fibres, measured as heat production with a new technique using a perfusion microcalorimeter, showed a median value of 0.40 mW/g, 25% lower than normal, p less than 0.02. Carnitine administration had no effect on several different tests of muscular function. Neurophysiologically, discrete improvements in the temperature responses were recorded, but no changes in sensory and motor nerve conduction velocities or in vibration thresholds were noted. No symptomatic improvement was observed even in patients with the lowest carnitine levels prior to treatment. Our data do not support the hypothesis that carnitine deficiency contributes to muscle and nerve dysfunction in patients on chronic haemodialysis.

Adult↗

Plasma lipoproteins, liver function and glucose metabolism in haemodialysis patients: lack of effect of L-carnitine supplementation.

The effects of L-carnitine administration (2 g i.v. three times weekly for 6 weeks) were studied in a double blind trial comprising 2 X 14 patients on regular haemodialysis treatment. The initial plasma carnitine concentrations were normal in the male, but slightly lowered in the female participants and rose more than ten-fold in the patients receiving active treatment. The majority (15/28) of patients had moderate hypertriglyceridaemia, whereas plasma HDL cholesterol levels were normal. Activities of hepatic and lipoprotein lipase were decreased and fat tolerance impaired. The S-triiodothyronine and/or thyroxine levels were subnormal in 11 patients. Four patients had fasting hyperinsulinemia, and 6 demonstrated abnormal B-glucose patterns after a peroral glucose load. The galactose elimination rate demonstrated moderately impaired hepatocyte function in four patients. No effects of carnitine treatment on any of the variables could be detected.

Adult↗

Carnitine and left ventricular function in haemodialysis patients.

Left ventricular function was non-invasively studied in 28 randomly selected haemodialysis patients before and after administration of L-carnitine, 2 g i.v. three times per week or saline in a double blind designed study over a six-week period. Cardiac function variables showed no relationship to muscle (vastus lateralis) and plasma carnitine concentrations. No apparent deficiency in muscle carnitine was found, whereas total plasma carnitine was lower in female patients than in female controls, p less than 0.002. The echocardiographic left ventricular end-diastolic diameter was initially increased in about one third and the ejection fraction was depressed in about one fifth of the patients. An increased A:H ratio was found in 15%. Systolic time intervals were deranged in 30% of the patients. After carnitine administration, marked increases of muscle and plasma carnitine levels were found, p less than 0.01, but no effects were recorded in any of the cardiac tests. Muscle carnitine increased from 14.6 mmol/kg dry weight to a median of 23.7 mmol/kg. We found no support for the hypothesis that carnitine depletion is responsible for cardiac dysfunction in haemodialysis patients.

Adult↗

Muscle and plasma carnitine levels and urinary carnitine excretion in multiply injured patients on total parenteral nutrition.

Carnitine is necessary for the transport of long-chain fatty acids across the mitochondrial membrane. Thirteen severely injured patients on total parenteral nutrition were studied during days 2-8 post injury. Initially plasma and skeletal muscle carnitine values were within the range earlier found for normal subjects, whereas the urinary carnitine excretion was markedly increased. On day 4 there was a simultaneous decrease in the carnitine concentration in plasma (alpha < 0.01) and urine (alpha < 0.05) as well as in skeletal muscle tissue (alpha < 0.05 using only the values that could be paired i.e. from eight subjects), whereas no difference was found between day 2 and 8. One explanation of this pattern might be that a redistribution of carnitine occurs to other organs not measured, for example the liver. In skeletal muscle tissue, statistically significant positive correlations were found between the carnitine level and ATP (alpha < 0.01) and phosphocreatine (alpha < 0.02) as well as between carnitine and glycogen (alpha < 0.05).

Journal Article↗

Fat metabolism following an intravenous bolus dose of a fat emulsion and carnitine.

Intravenous fat tolerance tests were performed with (carboxyl-14C)-triolein labelled Intralipid in four normal subjects with and without L-carnitine administration, 20 and 25 mg/kg body weight. The pharmacokinetics of L-carnitine was studied simultaneously with measurements of variables reflecting fat metabolism during 4 h. 3-OH-butyrate concentration in plasma was higher in all subjects when carnitine was given. No effect of carnitine was found in elimination of the exogenous triglycerides, the 14CO2 activity in expired air, concentration and specific radioactivity of non- esterified fatty acids or glucose in plasma. The data suggest that carnitine may slightly increase fatty acid oxidation in normal subjects provided that increase of 3-OH-butyrate concentration in plasma is the most sensitive variable reflecting fatty acid oxidation of the variables applied in this study.

Adult↗

Increase in stable glycosylated haemoglobin after induction of poor glycaemic control.

Eight insulin-treated diabetic patients in good glycaemic control were studied as out-patients with frequent determinations of stable glycosylated haemoglobin (HbA1c) before, during and after 1 week of induced poor glycaemic control. Stable HbA1c was determined by cation exchange chromatography after elimination of the labile fraction by incubation in saline (0.15 mol/l). The increase in mean blood glucose was significant on the first day of reduced insulin therapy and greatest after 1 week (6.9 +/- 3.9 mmol/l above basal values). Stable HbA1c increased significantly on day 7 of the reduced insulin treatment. The increase represented, on average, 0.009% of total haemoglobin per mmol/l increase in mean blood glucose per 24 h during the period of induced hyperglycaemia. After restoring insulin therapy, a significant decrease in blood glucose was achieved on day 1 and after 2 days, the blood glucose level was similar to before the study. There was no significant decrease in stable HbA1c within the first 2 weeks of improved glycaemia.

Adult↗

Urinary excretion of carnitine in multiply injured patients on different regimens of total parenteral nutrition.

Carnitine derives from intake of preformed exogenous carnitine and synthesis from lysine and methionine, but is absent in parenteral fluids. Urinary excretions of carnitine and its derivatives was measured in 30 patients 2-8 days after severe multiple injuries and compared with controls. The patients received five different isocaloric parenteral nutritional regimens;group 1 glucose and fat, group 2 glucose, fat and amino acids, group 3 glucose and insulin, group 4 glucose and amino acids, and group 5 branched-chain amino acids. The mean total carnitine excretion in healthy men was 420 mumol/24 h +/- 57 (SEM), and in women 266 mumol/24 h +/- 29, 41% of which was free carnitine. Mean excretion of total carnitine during days 2-8 after trauma for the five groups was: 900 +/- 100, 1169 +/- 112, 1251 +/- 102, 1023 +/- 117, and 668 +/- 128 mumol/24 h, being significantly higher in groups 1-4 than in healthy men. The free carnitine fraction in the patients was significantly higher than in controlled healthy subjects. Total carnitine excretion was unaffected by different nutritional regimens in the very first days. During days 6-8, group 5, receiving branched-chain amino acids had lower excretion of total carnitine (compared to groups 2-4) and free carnitine (compared to groups 3-4). Groups 3 and 4 excreted a higher percentage as free carnitine compared to the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acylation↗

Plasma and urine carnitine in children with diabetes mellitus.

L-Carnitine is essential for the transport of long chain fatty acids into mitochondria and, hence, in ketoacid production. Total, free and acylcarnitine in plasma and urine have been determined in 52 children and adolescents with insulin-dependent juvenile diabetes and compared with 72 controls. The subjects were divided into three age groups 8-10, 11-15 and 16-20 years. The plasma, total and free carnitine were significantly lower in diabetic patients than in controls in all age groups. Acylcarnitine was significantly higher in the diabetic patients than in the controls in the two younger age groups. No sex-related differences in plasma carnitine and its derivatives were found in the two younger groups. A statistically significant correlation coefficient was noted between glycosylated hemoglobin and the plasma acyl/free carnitine ratio, 2 p less than 0.05. The daily urinary excretion and renal clearance of carnitine and its derivatives showed few significant differences between the diabetic and the control subjects.

Adolescent↗

Rapid and slow rate of decrease in HbA1a + b and HbA1c during improved glycaemic control.

The change in glycosylated haemoglobins was studied with a column chromatographic method when glycaemic control was rapidly improved in nine diabetic patients. The patients were followed for 3 weeks or more. There was a decrease in HbA1a+b and HbA1c within the first few days of improved control and this decrease was faster than later on. The initial decrease of HbA1a+b was faster than that of HbA1c. In individual patients the initial decrease in glycosylated haemoglobins correlated with the initial rate of decrease in blood glucose. It is concluded that HbA1a+b and HbA1c decrease biphasically during improved glycaemic control. The rapid initial decrease may be due to labile HbA1 and it is large enough to influence the value of HbA1 as an indicator of long-term glycaemic control in some patients.

Adolescent↗

Effect of thyroxine treatment on carnitine levels in mice.

The effect in mice of 8 subcutaneous injections of 20 microgram of L-thyroxine at 12 hr-intervals on the carnitine concentration in the heart and skeletal muscle tissue was studied. In skeletal muscle tissue, the thyroxine treatment resulted in a depressed carnitine concentration. The mean values were 1.59 +/- 0.034 (S.E.M.) and 2.03 +/- 0.045 mumol/g noncollagen protein and 1.11 +/- 0.035 and 1.45 +/- 0.037 mumol/g dry weight for the thyroxine treated and the control animals, respectively. Thyroxine produced myocardial hypertrophy. The thyroxine treated animals had lower cardiac values when dry weight was used as reference base 4.17 +/- 0.10 mumol/g dry weight than the control group, 4.69 +/- 0.18 mumol/g dry weight. No statistically significant difference was found between the two groups when the cardiac carnitine concentration was expressed per g noncollagen protein or as carnitine in the entire hearts. Thus, thyroxine has been showed to influence the metabolism of carnitine in mice.

Animals↗