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Biomedical subjects

G Cederblad

Publications and source records attributed to G Cederblad.

At least 37 records · Page 2Linked to original sources
PubMed1991

Acetyl group accumulation and pyruvate dehydrogenase activity in human muscle during incremental exercise.

The changes in the muscle contents of CoASH and carnitine and their acetylated forms, lactate and the active form of pyruvate dehydrogenase complex were studied during incremental dynamic exercise. Eight subjects exercised for 3-4 minutes on a bicycle ergometer at work loads corresponding to 30, 60 and 90% of their VO2max. Muscle samples were obtained by percutaneous needle biopsy technique at rest, at the end of each work period and after 10 minutes of recovery. During the incremental exercise test there was a continuous increase in muscle lactate, from a basal value of 4.5 mmol kg-1 dry weight to 83 mmol kg-1 at the end of the final period. The active form of pyruvate dehydrogenase complex increased from 0.37 mmol acetyl-CoA formed per minute per kilogram wet weight at rest to 0.80 at 30% VO2max, 1.28 and 1.25 at 60 and 90% VO2max, respectively. Both acetyl-CoA and acetylcarnitine increased at the two highest work loads. The increase of acetyl-CoA was from 12.5 mumol kg-1 dry weight at rest to 27.3 after the highest work load and for acetylcarnitine from 6.0 mmol kg-1 dry weight to 15.2. The CoASH and free carnitine contents fell correspondingly. There was a close relationship between acetyl-CoA and acetylcarnitine accumulation in muscle during exercise, with a binding of approximately 500 mol acetyl groups to carnitine for each mole of acetyl-CoA accumulated. The results imply that the carnitine store in muscle functions as a buffer for excess formation of acetyl groups from pyruvate catalyzed by the pyruvate dehydrogenase complex.

Acetyl Coenzyme A↗
PubMed1990

Radioisotopic assays of CoASH and carnitine and their acetylated forms in human skeletal muscle.

Radioisotopic assays for the determination of acetyl-CoA, CoASH, and acetylcarnitine have been modified for application to the amount of human muscle tissue that can be obtained by needle biopsy. In the last step common to all three methods, acetyl-CoA is condensed with [14C]oxaloacetate by citrate synthase to give [14C]-citrate. For determination of CoASH, CoASH is reacted with acetylphosphate in a reaction catalyzed by phosphotransacetylase to yield acetyl-CoA. In the assay for acetylcarnitine, acetylcarnitine is reacted with CoASH in a reaction catalyzed by carnitine acetyltransferase to form acetyl-CoA. Inclusion of new simple steps in the acetylcarnitine assay and conditions affecting the reliability of all three methods are also described. Acetylcarnitine and free carnitine levels in human rectus abdominis muscle were 3.0 +/- 1.5 (SD) and 13.5 +/- 4.0 mumol/g dry wt, respectively. Values for acetyl-CoA and CoASH were about 500-fold lower, 6.7 +/- 1.8 and 21 +/- 8.9 nmol/g dry wt, respectively. A strong correlation between acetylcarnitine (y) and short-chain acylcarnitine (x), determined as the difference between total and free carnitine, was found in biopsies from the vastus lateralis muscle obtained during intense muscular effort, y = 1.0x + 0.5; r = 0.976.

Acetyl Coenzyme A↗
PubMed1990

The effect of carnitine supplementation on carnitine balance in patients with persistent post-operative infection.

The effect of L-carnitine (C) supplementation on body C balance, muscle C concentration, the leg exchange of C and some amino-acids was investigated in 8 patients with persistent post-operative infection. Before supplementation, total C concentration was 81 +/- 13 micromol/l plasma (SEM) and 15.4 +/- 1.5 micromol/g dry weight muscle, urinary excretion was 19 +/- 4 micromol/kg x 24 h and the arterial-femoral venous concentration difference over the leg (A-FV) of free C was -2.90 +/- 0.97 micromol/l, p < 0.05. Plasma-free C concentration correlated inversely with the A-FV of free C. The excretion of free C in urine was directly related to the plasma-free C concentration. A total C dose of 110 mg/kg during 4 days resulted in a 30% retention (range 12-48), a doubling of plasma C levels but no measurable alteration in either muscle C content or the arterial concentration and exchange of amino-acids over the leg. Plasma-free C concentration correlated inversely with the clearance of creatinine. In patients with persistent post-operative infection, muscle C concentration was normal and C was released from muscle as a consequence of muscle catabolism. The rate of C release was a major determinant of the plasma C concentration. At normal or low plasma C levels, the renal tubular reabsorption of C was a major determinant of body C balance. At elevated plasma concentrations of C, such as during C supplementation, the tubular capacity for reabsorption is exceeded and body carnitine balance is mainly dependent on the glomerular filtration.

Journal Article↗
PubMed1990

Low blood and plasma carnitine levels in children receiving long-term parenteral nutrition.

Total and free carnitine and acylcarnitine concentrations were analyzed in whole blood and plasma in 12 children with a mean age of 68.4 +/- 42.9 months who had received carnitine-free total parenteral nutrition (TPN) for an average of 4 years. The purpose of the study was to see if the children had become carnitine deficient and, if so, whether this correlated with poor lipid clearance. Compared to controls, the TPN-dependent children had significantly decreased concentrations of total and free carnitine in blood (26.6 +/- 9.4 (SD) mumols/L vs. 43.3 +/- 9.1 mumols/L, p less than 0.001, and 17.1 +/- 7.7 mumols/L vs. 35.2 +/- 8.1 mumols/L, p less than 0.001, respectively). Similar results were found in plasma (total carnitine of 19.0 +/- 8.0 mumols/L vs. 41.9 +/- 5.2 mumols/L, p less than 0.001, and free carnitine of 15.7 +/- 7.3 mumols/L vs. 36.1 +/- 5.2 mumols/L, p less than 0.001, respectively). The acylcarnitine concentration in plasma was decreased in the TPN children (3.3 +/- 1.5 mumols/L vs. 5.8 +/- 3.0 mumols/L, p less than 0.01) compared to controls. Despite the low carnitine concentrations, serum triglyceride levels and serum free fatty acid levels were within the normal range. There was no correlation between carnitine concentrations in plasma and serum triglyceride and free fatty acid levels. Our data show that children receiving carnitine-free TPN for many years developed markedly decreased concentrations of carnitine in blood and plasma. However, no adverse effects of the low carnitine levels were found on triglyceride and free fatty acid metabolism under stable conditions.

Carnitine↗
PubMed1990

Parenteral nutrition in preterm neonates with and without carnitine supplementation.

The effects of carnitine supplementation on fat and glucose metabolism and carnitine balance were studied in 12 preterm neonates receiving full or partial parenteral nutrition (PN) for 5 to 21 days. The gestational age ranged from 27 to 32 weeks and the birth weight from 790 to 2090 g. The neonates were assigned at random to receive either L-carnitine 10 mg/kg (n = 6) or saline (n = 6). In the carnitine group, increased concentrations in plasma of total and free carnitine were observed. Less than 50% of the given dose was recovered in urine. In the placebo group no changes in the total plasma carnitine concentration were seen. In all neonates plasma triglycerides, free fatty acids, glycerol, alanine, 3-hydroxybutyrate (BOB), glucose and lactate were measured at predetermined intervals. The only significant difference between the groups was higher BOB-concentrations in the carnitine group 2 days after the start of parenteral nutrition. Elevated BOB concentrations are an indicator of improved fatty acid oxidation in the carnitine group. In this study, only a temporary effect of the carnitine supplementation was found.

Alanine↗
PubMed1990

Association between muscle acetyl-CoA and acetylcarnitine levels in the exercising horse.

Treadmill exercise of 2-min duration and increasing intensity resulted in increased formation of acetyl-CoA and acetylcarnitine in working muscle of Thoroughbred horses. At high work intensities a plateau was reached for both acetyl-CoA (approximately 50 mumols/kg dry muscle) and acetylcarnitine (approximately 20 mmol/kg dry muscle). Postexercise concentrations were significantly (P less than 0.001) correlated; [acetylcarnitine] = 349.[acetyl-CoA] + 2.4. The results indicate that approximately 350 mumols acetylcarnitine were accumulated for every 1 mumol acetyl-CoA. Under the conditions of exercise used it is probable that most of the acetyl-CoA formed is generated through the intramitochondrial decarboxylation of pyruvate. The acetyl groups of acetyl-CoA are apparently redistributed throughout the whole cell through formation of acetylcarnitine, which readily transverses the mitochondrial membrane. Despite the redistribution, however, the close correlation between acetylcarnitine and acetyl-CoA would indicate that equilibrium was maintained and that neither acetylcarnitine transferase nor carnitine/acetylcarnitine translocase were rate limiting. There is some question as to whether the changes observed relate directly to exercise itself or to the state in muscle 10 s or more after exercise.

Acetyl Coenzyme A↗
PubMed1989

Muscle alkali-soluble protein, carnitine, water and electrolytes in patients with persistent post-operative infection.

The muscle contents of water, electrolytes, creatine, alkali-soluble protein (ASP) and carnitine were determined using percutaneous muscle biopsy technique. Seven patients with prolonged catabolic states and subsequent respiratory failure were studied. Twelve age- and sex-matched healthy subjects were used for comparison. The muscle content of alkali-soluble protein in relation to the content of DNA was less than half of control values, indicating a loss of more than 50% of muscle protein content. The muscle carnitine content was 25.9 +/- 6.5 mumol/g alkali-soluble protein, suggesting a preserved muscle carnitine concentration. Total muscle water was increased by over 20%, mainly due to an increase in extracellular water. Muscle sodium and chloride contents were doubled. The content of magnesium was slightly reduced but muscle potassium was normal. The marked depletion of muscle protein may have contributed to the requirements for artificial ventilation and the difficulties in weaning off the ventilator. The increase in muscle water masks the loss of metabolically active muscle tissue yielding low values for energy expenditure when relating to body weight. The benefit of the use of the ASP/DNA ratio in nutritional assessment is emphasised.

Journal Article↗
PubMed1989

Effect of carnitine supplemented TPN on turnover and muscle utilisation of free fatty acids in patients with persistent post-operative infection.

The effect of L-carnitine on FFA turnover and regional utilisation over the leg was investigated using infusion of 14C-oleic acid and measurement of the respiratory quotient (RQ) in eight artificially ventilated patients with severe post-operative infection and at least 2 weeks of carnitine free TPN. Carnitine or placebo was added to the daily infusion of lipid during two consecutive 4-day periods in a randomised cross-over fashion. The total dose of carnitine was 110 mg/kg over 4 days. Before carnitine supplementation, total plasma carnitine levels ranged between 39 and 152 micromol/l. The RQ was 0.87 +/- 0.02 (SEM). The turnover (185 +/- 64 micromol/min) and fractional turnover (0.39 +/- 0.04/min) of oleic acid as well as the uptake (31 +/- 10 micromol/min) and fractional uptake (0.46 +/- 0.05) over the leg were similar to previously reported values in healthy subjects. Carnitine supplementation, despite a doubling of the average plasma carnitine level, did not influence the RQ or the whole body turnover and regional exchange of oleic acid. The present results suggest that four days of carnitine supplementation in patients with persistent post-operative infection has no measurable effect on FFA utilisation, indicating that the patients' carnitine reserves were sufficient to maintain normal FFA utilisation.

Journal Article↗
PubMed1988

Pharmacokinetics of bolus intravenous and oral doses of L-carnitine in healthy subjects.

The pharmacokinetics of single intravenous and oral doses of L-carnitine 2 and 6 g was studied in 6 healthy subjects on a low-carnitine diet. Carnitine was more rapidly eliminated from plasma after the 6 g dose. Comparing the doses, the t1/2 beta of the elimination phase (beta) was 6.5 h vs 3.9 h, the elimination constant 0.40 vs 0.50 h-1 and the plasma carnitine clearance was 5.4 vs 6.11.h-1 for the 2 g and 6 g doses, respectively, showing dose-related elimination. Saturable kinetics were not found. The apparent volumes of distribution after the two doses were not significantly different and were of the same order as the total body water. Urinary recoveries of the 2 g and 6 g doses were 70% and 82%, respectively, during the first 24 h. Following the oral doses, there was no significant difference between the areas under the plasma carnitine concentration-time curves. Urinary recovery was 8% and 4% for the 2 g and 6 g doses during the first 24 h. Oral bioavailability was 16% for the 2 g dose and 5% for the 6 g dose. The results suggest that the mucosal absorption of carnitine was already saturated by the 2 g dose.

Administration, Oral↗
PubMed1988

Pharmacokinetics of intravenous and oral bolus doses of L-carnitine in healthy subjects.

The pharmacokinetics of single intravenous and oral doses of L-carnitine 2 g and 6 g has been investigated in 6 healthy subjects on a low carnitine diet. Carnitine was more rapidly eliminated from plasma after the higher dose. Comparing the 2-g and 6-g doses, the t1/2 beta of the elimination phase (beta) was 6.5 h vs 3.9 h, the elimination constant was 0.40 vs 0.50 h-1 and the plasma carnitine clearance was 5.4 vs 6.1 1 x h-1 (p less than 0.025), thus showing dose-related elimination. Saturable kinetics was not found in the range of doses given. The apparent volumes of distribution after the two doses were not significantly different and they were of the same order as the total body water. Urinary recoveries after the 2-g and 6-g doses were 70% and 82% during the first 24 h, respectively. Following the two oral dosing, there was no significant difference in AUCs of plasma carnitine. Urinary recoveries were 8% and 4% for the 2-g and 6-g doses during the first 24 h. The oral bioavailability of the 2-g dose was 16% and of the 6 h dose 5%. The results suggest that the mucosal absorption of carnitine is already saturated at the 2-g dose.

Administration, Oral↗
PubMed1988

Influence of carnitine supplementation on muscle substrate and carnitine metabolism during exercise.

We examined 1) the effect of L-carnitine supplementation on free fatty acid (FFA) utilization during exercise and 2) exercise-induced alterations in plasma levels and skeletal muscle exchange of carnitine. Seven moderately trained human male subjects serving as their own controls participated in two bicycle exercise sessions (120 min, 50% of VO2max). The second exercise was preceded by 5 days of oral carnitine supplementation (CS; 5 g daily). Despite a doubling of plasma carnitine levels, with CS, there were no effects on exercise-induced changes in arterial levels and turnover of FFA, the relation between leg FFA inflow and FFA uptake, or the leg exchange of other substrates. Heart rate during exercise after CS decreased 7-8%, but O2 uptake was unchanged. Exercise before CS induced a fall from 33.4 +/- 1.6 to 30.8 +/- 1.0 (SE) mumol/l in free plasma carnitine despite a release (2.5 +/- 0.9 mumol/min) from the leg. Simultaneously, acylated plasma carnitine rose from 5.0 +/- 1.0 to 14.2 +/- 1.4 mumol/l, with no evidence of leg release. Consequently, total plasma carnitine increased. We concluded that in healthy subjects CS does not influence muscle substrate utilization either at rest or during prolonged exercise and that free carnitine released from muscle during exercise is presumably acylated in the liver and released to plasma.

3-Hydroxybutyric Acid↗
PubMed1987

Effect of diet on plasma carnitine levels and urinary carnitine excretion in humans.

This investigation determines the effect of two isocaloric diet regimens on plasma carnitine and urinary carnitine excretion in man. Seven healthy men were served a high-carbohydrate, low-fat (C) or a low-carbohydrate, high-fat (F) diet for 2 wk, ie, one diet regimen for 4 d followed by a 3-d break and concluded with 4 d more on the other diet regimen. The two regimens contained the same amount of carnitine-rich food. Plasma free carnitine rose significantly from the initial value on F diet and was significantly higher from day 3 than C diet. Plasma acyl carnitine increased on both diets. Urinary excretion of carnitine increased only on F diet. Renal clearance of both free and acyl carnitine was significantly greater on F diet than on C diet. Results showed that composition of a diet with constant carnitine content influenced carnitine metabolism in man.

Adult↗
PubMed1986

Carnitine levels in skeletal muscle of malnourished patients before and after total parenteral nutrition.

Carnitine is necessary for the transport of long-chain fatty acids across the mitochondrial membrane. Carnitine is derived from the diet and from endogenous synthesis from lysine and methionine. About 98% of the body's carnitine pool is located in skeletal muscle tissue. Skeletal muscle carnitine levels were determined in two groups of malnourished patients, eight patients with anorexia nervosa with a weight loss of 32.4% +/- 1.8 (mean +/- SEM) and six surgical patients with major gastrointestinal disorders and a weight loss of 15.2% +/- 2.7. Their hepatic and kidney functions were normal. On admission, the muscle carnitine levels were 16.9 +/- 4.0 mumol/g dry weight (mean +/- SD) for the surgical patients and 20.8 +/- 5.0 mumol/g dry weight for the anorexia nervosa patients, which corresponded to carnitine levels seen in healthy subjects. No statistical significance was found between the two groups. Total parenteral nutrition was given to the surgical patients for 2 weeks and to the anorexia nervosa patients for 3-5 weeks. No statistical difference in muscle carnitine levels was found in either group after nutritional support. These malnourished patients had no decreased muscle carnitine levels on admission and maintained them during several weeks of total parenteral nutrition.

Journal Article↗
PubMed1986

Extrusion cooking of a high-fibre cereal product. 2. Effects on apparent absorption of zinc, iron, calcium, magnesium and phosphorus in humans.

1. The effect of extrusion cooking, using mild conditions, of a high-fibre cereal product on apparent small bowel absorption of zinc, iron, calcium, magnesium and phosphorus was studied. 2. Seven ileostomy subjects were studied during two periods (each of 4 d), on a constant low-fibre diet supplemented with either 54 g/d of a bran-gluten-starch mixture or the corresponding extruded product. 3. The apparent absorption of Zn, Mg and P was significantly decreased (P less than 0.05) during the period with extruded product compared with the period with bran-gluten-starch. No difference was found for Fe and Ca. 4. The negative effect of extrusion cooking of a product containing phytic acid on availability of Zn, Mg and P was small but could be of nutritional relevance in foodstuffs that are consumed frequently and in infant formulas.

Absorption↗
PubMed1986

Plasma carnitine and renal-carnitine clearance during pregnancy.

This study assessed the time course of decrease in plasma carnitine during pregnancy and compared the renal clearance of carnitine during late pregnancy with nonpregnant women. As early as the 8th wk of pregnancy, the mean (+/- SD) value of total plasma-carnitine concentration in 19 women was significantly decreased from 39.0 +/- 6.3 to 32.8 +/- 4.6 mumol/l and the values continued to fall to 17.3 mumol/l by the 36th wk. The pattern was due to a fall in free-carnitine level; acylcarnitine remained unchanged. In 12 other women examined during late pregnancy, the renal clearance of acylcarnitine was significantly higher than in nonpregnant women, 53.9 +/- 29.4 versus 13.3 +/- 3.0 ml/min, in contrast to free carnitine, 3.5 +/- 2.8 versus 2.8 +/- 1.9 ml/min. Urinary excretion of carnitine (expressed per mol creatinine) did not differ between the two groups. Pregnant women showed sustained excretion of carnitine in the presence of low plasma-carnitine concentrations.

Adult↗
PubMed1986

Haematological findings in chronic alcoholics after heavy drinking with special reference to haemolysis.

Haematological abnormalities are frequently found in heavy-drinking chronic alcoholics, but anaemia is generally a rare complication. When present, haemolysis is considered to be one of the most common causes. However, little is known about mild haemolysis without anaemia. The present report on eighteen male chronic alcoholics with a recent heavy debauche but without signs of severe liver disease gave support for the occurrence of a reversible low-degree haemolysis without concomitant gross changes of the erythrocytes. Thus the bone marrow showed an increased erythropoiesis in the absence of iron deficiency and known blood losses. Further, increased reticulocyte counts and low levels of haemopexin were noted in the early abstinence. Finally, during the withdrawal phase haptoglobin and haemopexin increased concomitantly with diminishing values of unconjugated bilirubin. The most likely cause of the proposed diminished red cell survival before the withdrawal is supposed to be a reduced membrane stability.

Adult↗
PubMed1986

Plasma fibronectin concentration in suspected septicaemia is related to severity of sepsis.

Low plasma fibronectin levels have been reported in patients with septic complications following surgery, major trauma or burn injury. Our purpose was to evaluate fibronectin in suspected septicaemia and its relationship to severity of infection and clinical outcome. In 51 consecutive patients with infection classified as mild (group A), severe (group B) or severe complicated by septic shock, disseminated intravascular coagulation or multiple organ failure (group C), the respective mean initial fibronectin concentrations were 85% +/- 10 (SD), 55% +/- 15 and 44% +/- 13 of the reference mean (0.35 g/l). In statistical analysis the groups differed significantly from each other and from controls. All 11 patients with mild infection had fibronectin values above the lower reference limit, which was 60%, whereas in 15 of 16 group C patients and all seven fatal cases in that group the initial fibronectin values were below 60%. Plasma fibronectin rose with clinical improvement, but remained low in patients with persisting septicaemia. The results confirmed earlier reports of low fibronectin levels in septic states, and indicate that low concentration is of prognostic value and is related to the severity of the disease.

Adolescent↗