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Biomedical subjects

J Wernerman

Publications and source records attributed to J Wernerman.

At least 127 records · Page 7Linked to original sources
PubMed1990

Trauma metabolism and the heart: studies of heart and leg amino acid flux after cardiac surgery.

Flux of plasma amino acids was measured across the heart and the leg (reflecting mainly skeletal muscle) in 18 patients 1 hour after completion of aorto-coronary bypass surgery. There was a net loss of amino acids from the leg (-324.9 +/- 39 nmol/min/100 ml tissue) while amino acid flux across the heart was not statistically different from zero. There were however positive intertissue correlations between leg and myocardial flux of tyrosine and most other amino acids, suggesting that protein metabolism of both tissues were affected in the same catabolic direction by the trauma response. Alanine and glutamine accounted for 50% of the amino acid release from the leg, which is in accordance with observations in association with other types of trauma. Alanine and glutamine also dominated amino acid release from the heart. Glutamate and aspartate were taken up by both tissues. The principal difference between the tissues was a myocardial uptake of leucine and isoleucine, in contrast to a leg release.

Adult↗
PubMed1990

Alanyl-glutamine counteracts the depletion of free glutamine and the postoperative decline in protein synthesis in skeletal muscle.

Skeletal muscle protein and amino acid metabolism change after surgical trauma during a period characterized by skeletal muscle protein catabolism. Available total parenteral nutrition (TPN) not containing glutamine does not prevent these changes, while TPN enriched with glutamine has been shown to have beneficial effects on postoperative skeletal muscle protein metabolism. Glutamine, in the form of a dipeptide, alanyl-glutamine, was added to TPN. Patients undergoing elective cholecystectomy were given postoperative TPN. Two groups received isocaloric and isonitrogenous conventional TPN, one group with (n = 8) and the other without an addition of alanyl-glutamine (n = 8). Skeletal muscle protein metabolism was studied in muscle biopsy specimens from which the muscle free amino acid pattern and the concentration and size distribution of ribosomes, serving as a measure of protein synthesis, were determined. In the control group, muscle free glutamine decreased by 38.8% +/- 6.6% and the polyribosome concentration per mg of DNA decreased by 21% +/- 5.2% after operation. In the group given TPN supplemented with alanyl-glutamine, these two parameters of muscle protein and amino acid metabolism did not change significantly. Compared to the control group, whole-body nitrogen balance was improved after operation by the addition of alanyl-glutamine to TPN (p less than 0.01). Muscle free glutamine and muscle protein synthesis were preserved after operation and the whole-body nitrogen balance was improved by adding glutamine in the form of alanyl-glutamine to TPN. The dipeptide alanyl-glutamine seems to be a suitable means of providing glutamine in a stable form.

Cholecystectomy↗
PubMed1989

Glutamine and ornithine-alpha-ketoglutarate but not branched-chain amino acids reduce the loss of muscle glutamine after surgical trauma.

The concentration of free glutamine in skeletal muscle decreases characteristically after surgical trauma. In animal studies a correlation between muscle protein synthesis and the glutamine concentration is reported. For pharmaceutical reasons, commercially available amino acid solutions do not contain glutamine. Therefore, at present, postoperative total parenteral nutrition does not provide glutamine. Several modifications of the composition of the amino acid solutions given in total parenteral nutrition have been evaluated recently. Ornithine-alpha-ketoglutarate preserves muscle protein synthesis and spares nitrogen after elective surgery, and an extra supply of branched-chain amino acids improves muscle protein synthesis in animals. Patients undergoing elective abdominal surgery (n = 33) received isocaloric (135 kJ/kg body weight/24 h) and isonitrogenous (0.2 g N/kg body weight/24 h) total parenteral nutrition for three days immediately following surgery. Administration of glutamine and ornithine-alpha-ketoglutarate as part of the amino acid supply reduced the loss of muscle glutamine from 40% to 25% (P less than .05). Additional supplementation of branched-chain amino acids produced no such effect, however, as compared with the control group. Further clinical trials including glutamine and ornithine-alpha-ketoglutarate are advocated.

Abdomen↗
PubMed1989

Utilization of intravenously administered N-acetyl-L-glutamine in humans.

L-glutamine is too unstable for inclusion in solutions for parenteral nutrition, but its acetylated analogue, N-acetyl-L-glutamine is not. The purpose of this three-part study was to investigate the utilization of intravenously (IV) administered acetylglutamine in humans. In study 1, nine healthy postabsorptive subjects were given 9.4 g acetylglutamine IV during four hours. In study 2, five healthy subjects were studied on two occasions following an overnight fast. They were given 9.4 g of acetylglutamine or an equivalent amount of glutamine as part of a total parenteral nutrition (TPN) regimen during 7.2 hours. A control group of five subjects was given the same TPN regimen, but without acetylglutamine or glutamine. The nutrient solution included glucose, amino acids, and a fat emulsion, supplying 9.4 g nitrogen and 6,300 kJ in a total volume of 1.8 L. In study 3, four patients were studied the day after major surgery. They were given the same TPN regimen as in study 2, containing 9.4 g acetylglutamine, during 7.2 hours. Plasma concentrations and urinary excretion of acetylglutamine and glutamine were measured in all three studies, and so were splanchnic and renal exchange of acetylglutamine and glutamine in study 1. In study 1, the plasma concentration of glutamine rose from 594 +/- 28 mumol/L to 728 +/- 26 mumol/L (P less than .001), whereas plasma levels of acetylglutamine exceeded 1,000 mumol/L in all subjects at the end of infusion. The eight-hour urinary excretion of acetylglutamine and glutamine corresponded to 18% of the infused amount of acetylglutamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

O6-methylguanine-DNA methyltransferase content in human lymphocytes following surgical trauma.

O6-methylguanine-DNA methyltransferase removes methyl groups from the O-6 position of guanine in DNA previously alkylated by alkylating carcinogens. Thus, the protein facilitates restoration of the impaired DNA. The content of O6-methylguanine-DNA methyltransferase was assayed in circulating lymphocytes and the impact of surgical trauma investigated. Patients (n = 13) without metabolic diseases admitted for elective orthopedic surgery were used. The patients were allowed water and food postoperatively. Blood was taken before and 3 days following surgery and the circulating lymphocytes were isolated. Before surgery, the O6-methylguanine-DNA methyltransferase content determined in the cell extracts showed patient-specific variations. Following surgery, a significant decrease of the protein by 60% (from 609 to 243 fmole/mg of DNA) was observed. The intensity of surgical trauma was confirmed by the decrease in plasma albumin concentration and the increase in white blood cell counts. The surgical trauma might elicit its effect as either a change in turnover of O6-methylguanine-DNA methyltransferase or a release from the thymus of lymphocytes low in enzyme levels. In summary, the surgical trauma per se was the cause of the pronounced decrease in the O6-methylguanine-DNA methyltransferase seen here. Investigations on O6-methylguanine-DNA methyltransferase levels have an important relevance in studies on tumor-promoting agents inhaled and then taken up by the T lymphocytes of prospective proliferating capacity.

Aged↗
PubMed1989

Availability of amino acids supplied by constant intravenous infusion of synthetic dipeptides in healthy man.

1. A commercial amino acid solution supplemented with two synthetic dipeptides, L-alanyl-L-glutamine (Ala-Gln) and glycyl-L-tyrosine (Gly-Tyr), or alternatively with isonitrogenous amounts of free alanine and glycine has been continuously infused over 4 h in six apparently healthy volunteers. 2. The infusion of the solutions was not accompanied by any side effects and the volunteers reported no complaints. 3. Infusion of the alanine- and glycine-supplemented control solution resulted in an increase of the concentration of these amino acids, while no appreciable change in free glutamine concentration was observed and free tyrosine revealed a steady decrease throughout the infusion. 4. Infusion of the peptide-supplemented solution resulted in a prompt equimolar liberation of the constituent free amino acids (glutamine, alanine, tyrosine and glycine), approaching steady state after about 30 min infusion, while only trace but stable concentrations of the two dipeptides were measured throughout the infusion. No peptides were detectable in urine. The findings suggest a nearly quantitative extracellular hydrolysis of the infused dipeptides and indicate a subsequent utilization of the liberated free amino acids. 5. The estimated metabolic clearance rates and total body plasma clearances were very similar for the two dipeptides (Ala-Gln 35.9 +/- 9.5 ml min-1 kg-1 and 2.9 +/- 0.9 l/min, respectively; Gly-Tyr 33.7 +/- 9.5 ml min-1 kg-1 and 2.7 +/- 0.9 l/min, respectively); thus there is little difference in the metabolic handling of these dipeptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Measurement of the rate of protein synthesis in muscle of postabsorptive young men by injection of a 'flooding dose' of [1-13C]leucine.

1. The 'flooding dose' technique for measuring the rate of protein synthesis in tissues in vivo involves the injection of a large amount of unlabelled amino acid together with the tracer to minimize differences in isotopic enrichment of the free amino acid in plasma and tissue compartments. This approach has been investigated in human muscle by taking biopsies from postabsorptive male volunteers given [1-13C]leucine. 2. Intravenous injection of 4 g of unlabelled leucine resulted in a rapid rise in free leucine concentration of seven- to eleven-fold in plasma and five-fold in muscle. Values were still elevated by two-fold after 2 h. 3. Five minutes after injection of [1-13C]leucine (0.05 g/kg) the isotopic enrichment of plasma leucine was 82% that of the injected material, falling to 44% at 120 min. The enrichment of free leucine in sequential muscle biopsies was close to that in plasma and almost identical to that for plasma alpha-ketoisocaproate. 4. The rate of protein synthesis was determined from the increase in leucine enrichment in protein of muscle biopsies taken before and 90 min after injection of [1-13C]leucine (0.05 g/kg; 19 or 39 atom% excess) and the average plasma alpha-ketoisocaproate enrichment over this period (taken to represent muscle free leucine). The mean rate of muscle protein synthesis in 10 subjects was 1.95 (SEM 0.12) %/day. Rates of protein synthesis calculated from plasma leucine as precursor enrichment were only 5% lower than those calculated from plasma alpha-ketoisocaproate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Stress hormones given to healthy volunteers alter the concentration and configuration of ribosomes in skeletal muscle, reflecting changes in protein synthesis.

1. The influence of elevated concentrations of stress hormones on the concentration of ribosomes and the relative proportion of polyribosomes, reflecting protein synthesis in vivo, in human skeletal muscle was investigated. Healthy volunteers were given a 6 h infusion of adrenaline (n = 8), cortisol (n = 8), a triple-hormone combination of adrenaline, cortisol and glucagon (n = 8), or saline (n = 8). 2. The total ribosome concentration declined by 30.4 +/- 7.2% in the triple-hormone group (P less than 0.01), by 26.9 +/- 8.6% in the cortisol group (P less than 0.05) and by 24.8 +/- 11.2% in the adrenaline group (P less than 0.05). The proportion of polyribosomes to total ribosomes decreased by 8.5 +/- 2.2% in the triple-hormone group (P less than 0.05). 3. During hormone infusion the serum glucose levels were enhanced. The insulin concentrations in serum were elevated in the adrenaline group and the triple-hormone group, but not in the cortisol group. Serum insulin decreased in the control group. 4. The results indicate an effect of the combined stress hormone infusion on the total ribosome concentration as well as on the relative abundance of polyribosomes. The single hormones influenced the total ribosome concentration only. The results suggest a critical role for stress hormones in producing the decline in muscle protein synthesis seen after trauma.

Adult↗
PubMed1989

Addition of glutamine to total parenteral nutrition after elective abdominal surgery spares free glutamine in muscle, counteracts the fall in muscle protein synthesis, and improves nitrogen balance.

Twenty-two patients undergoing elective abdominal surgery were given total parenteral nutrition (TPN) after the operation. The TPN contained either a conventional amino acid solution supplemented with glutamine or a conventional amino acid solution without supplementation. To study amino acid and protein metabolism, muscle biopsy specimens were taken before surgery and on the third postoperative day. The postoperative decrease in the intracellular concentration of free glutamine was less pronounced in the glutamine group (21.8 +/- 5.5%) than in the control group (38.7 +/- 5.1%; p less than 0.05). The protein synthesis was reflected in the concentration and size distribution of ribosomes. No significant changes in these parameters were seen in the glutamine group after the operation. In the control group, the total concentration of ribosomes fell by 27.2 +/- 8.5% (p less than 0.05), and the relative proportion of polyribosomes fell by 10.6 +/- 2.9% (p less than 0.01). Although there were significant changes in the control group, no significant differences in the changes of these parameters between the two groups were detected. The cumulative nitrogen loss was significantly less in the glutamine group as compared to the control group during the period studied--2.3 +/- 1.4 g versus 8.5 +/- 1.5 g, respectively (p less than 0.01). Administration of glutamine to catabolic patients is advocated.

Cholecystectomy↗
PubMed1988

Availability of amino acids supplied intravenously in healthy man as synthetic dipeptides: kinetic evaluation of L-alanyl-L-glutamine and glycyl-L-tyrosine.

1. For the first time utilization of intravenously administered L-alanyl-L-glutamine and glycyl-L-tyrosine was investigated by means of their kinetic behaviour after bolus injection in 10 and 11 apparently healthy male subjects (age 26.6 +/- 5.7 years), respectively. 2. The injection of the synthetic dipeptides was not accompanied by any side effects or complaints. 3. The synthetic dipeptides L-alanyl-L-glutamine and glycyl-L-tyrosine were rapidly cleared from plasma. By applying a monoexponential model the elimination half-lives were found to have very similar values (3.8 +/- 0.5 and 3.4 +/- 0.3 min) whether alanine or glycine was occupying the N-terminal position. The estimated volume of distribution was approximately that of the extracellular space. 4. Peptide disappearance was accompanied by a prompt equimolar increase in the concentrations of the constituent amino acids alanine and glutamine as well as glycine and tyrosine. 5. The study provides firm evidence that L-alanyl-L-glutamine and glycyl-L-tyrosine are rapidly (quantitatively) hydrolysed. The results of this study may indicate a safe and efficient parenteral use of the investigated peptides as sources of free glutamine and free tyrosine.

Adult↗
PubMed1988

Protein synthesis assessed by ribosome analysis in human papillary muscle in relation to oxidative capacity: a comparison with skeletal muscle.

Protein synthesis as assessed by the concentration and size distribution of ribosomes was determined together with citrate synthase activity in papillary muscles obtained at open heart surgery from patients with mitral valve disease. The results were compared with corresponding data from the quadriceps femoris muscle of patients undergoing cholecystectomy. Citrate synthase activity was six times higher in papillary muscle than in skeletal muscle. The total ribosome concentration per mg DNA was similar in the two types of muscle. Compared with skeletal muscle, in papillary muscle polyribosomes constituted a higher proportion of the ribosomes (p less than 0.001), and there was a tendency towards larger polyribosome aggregates. It is proposed that the high concentration of polyribosomes in papillary muscle is related to the high oxidative capacity of that tissue.

Citrate (si)-Synthase↗