Search PubMed⌕ Search

Biomedical subjects

J Wernerman

Publications and source records attributed to J Wernerman.

At least 91 records · Page 5Linked to original sources
PubMed1995

Alpha-ketoglutarate for myocardial protection in heart surgery.

A low myocardial content of alpha-ketoglutarate during heart surgery might aggravate ischaemic injury. 24 men undergoing coronary surgery participated in a randomised controlled study. 28 g alpha-ketoglutarate was added to blood cardioplegia for intermittent antegrade intracoronary perfusion in 13 cases. alpha-ketoglutarate reduced the appearance in blood of the ischaemic markers creatine kinase MB and troponin T (at 4 h after release of aortic cross-clamp; median [95% CI] 49 [37-60] micrograms/L in controls vs 32 [27-37] micrograms/L for creatine kinase MB, 2.0 [1.2-2.8] vs 1.1 [0.8-1.4] micrograms/L for troponin T). These findings signify attenuated ischaemic injury, possibly secondary to enhanced myocardial oxidative capacity.

Aged↗
PubMed1995

Glutamine and alpha-ketoglutarate prevent the decrease in muscle free glutamine concentration and influence protein synthesis after total hip replacement.

After surgical trauma, protein synthesis, as well as the concentration of free glutamine in muscle, decreases. Total parenteral nutrition (TPN) alone does not prevent the decrease of glutamine in muscle, but TPN supplemented with glutamine or its precursor, alpha-ketoglutarate, maintains amino acid concentration in muscle and preserves protein synthesis. The aim of this study was to characterize a human trauma model using patients undergoing total hip replacement, and furthermore to investigate whether glutamine or alpha-ketoglutarate alone without TPN can prevent the postoperative decrease in muscle free glutamine. Metabolically healthy patients undergoing total hip replacement were randomized into three groups. The control group (n = 13) received glucose 2 g/kg body weight (BW) during surgery and the first 24 postoperative hours. The glutamine group (n = 10) received glucose 2 g/kg BW and glutamine 0.28 g/kg BW, and the alpha-ketoglutarate group (n = 10) received glucose 2 g/kg BW and alpha-ketoglutarate 0.28 g/kg BW. Muscle biopsies were performed before surgery and 24 hours postoperatively. Free glutamine concentration in muscle decreased from 11.62 +/- 0.67 to 9.80 +/- 0.36 mmol/kg wet weight in the control group (P < .01), whereas it remained unchanged in both the glutamine group and alpha-ketoglutarate group. Protein synthesis, as reflected by the concentration of total ribosomes, decreased significantly in the control group, but not in glutamine and alpha-ketoglutarate groups. Polyribosome concentration decreased significantly in both the control and alpha-ketoglutarate groups. Total hip replacement can be used as a reproducible trauma model, with characteristic changes in the muscle amino acid pattern and protein synthesis 24 hours postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1995

The effects of a new amino-acid dipeptide solution on nitrogen balance and humoral growth factors in the postoperative state in man.

27 patients admitted for elective abdominal surgery were allocated to receive postoperative total parenteral nutrition supplemented with glutamine (glycyl-glutamine) and tyrosine (glycyl-tyrosine) containing dipeptides (DP-Gln 20; 0.16 g glutamine/kg BW/24 h) or isonitrogenous Vamin 18 for 5 days. The aim was to evaluate safety and effects on short-life plasma proteins, nitrogen balance, 3-methylhistidine excretion and alimentary growth factors in plasma. No differences in transthyretin or retinol binding protein levels, nitrogen balance or 3-methylhistidine excretion were found in patients receiving DP-Gln 20 compared to Vamin 18. There were higher plasma levels of peptide YY in the dipeptide group 5 days after surgery (p < 0.05). A correlation between insulin levels and nitrogen balance was found only in DP-Gln 20 treated patients day 6 (r = 0.91, p < 0.01). DP-Gln 20 is a glutamine dipeptide (Gly-Gln) containing amino acid solution which is considered safe in the postoperative state in man. No beneficial effects on whole body protein metabolism were found by adding DP-Gln 20 to total parenteral nutrition.

Journal Article↗
PubMed1995

Human skeletal muscle protein: effect of malnutrition, elective surgery and total parenteral nutrition.

1. The concentration of alkali-soluble protein, DNA and RNA in percutaneous muscle biopsy specimens was analysed. Tissue alkali-soluble protein/DNA ratio is a measure of muscle protein concentration, while tissue RNA/DNA ratio may reflect the capacity for protein synthesis. 2. Patients with weight loss due to cancer (n = 6) were compared with metabolically healthy patients before elective surgery (n = 7). Alkali-soluble protein/DNA and RNA/DNA ratios in the weight loss group were 248 (14) g/g and 1.3 (0.1) g/g respectively as compared with 404 (13) g/g and 2.1 (0.1) g/g in otherwise healthy patients. All of the alkali-soluble protein/DNA ratios and 5/6 of the RNA/DNA ratios in the weight loss group were below the 95% confidence interval for the healthy control subjects. 3. Patients undergoing elective open cholecystectomy (n = 7) were studied preoperatively and on days 3, 10, 20 and 30 post-operatively. The alkali-soluble protein/DNA ratio remained unchanged on post-operative day 3 but decreased by 8.7% (P < 0.01), 9.6% (P < 0.05) and 20.4% (P < 0.01) on days 10, 20 and 30 respectively in patients eating at will after the operation. No significant post-operative changes in alkali-soluble protein/DNA ratio were seen in patients given post-operative total parenteral nutrition with (n = 9) or without (n = 7) glycyl-glutamine supplementation for 3 days after surgery. 4. In conclusion, patients with weight loss due to malignant disease have a low muscle protein concentration. Elective surgery of medium magnitude results in a decrease in muscle protein lasting for more than 30 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Laparoscopic cholecystectomy does not prevent the postoperative protein catabolic response in muscle.

OBJECTIVE: The authors determined the effect of laparoscopic cholecystectomy on protein synthesis in skeletal muscle. In addition to a decrease in muscle protein synthesis, after open cholecystectomy, the authors previously demonstrated a decrease in insulin sensitivity. This study on patients undergoing laparoscopic and open surgery, therefore, included simultaneous measurements of protein synthesis and insulin sensitivity. SUMMARY BACKGROUND DATA: Laparoscopy has become a routine technique for several operations because of postoperative benefits that allow rapid recovery. However, its effect on postoperative protein catabolism has not been characterized. Conventional laparotomy induces a drop in muscle protein synthesis, whereas degradation is unaffected. METHODS: Patients were randomized to laparoscopic or open cholecystectomy, and the rate of protein synthesis in skeletal muscle was determined 24 hours postoperatively by the flooding technique using L-(2H5)phenylalanine, during a hyperinsulinemic normoglycemic clamp to assess insulin sensitivity. RESULTS: The protein synthesis rate decreased by 28% (1.77 +/- 0.11%/day vs. 1.26 +/- 0.08%/day, p < 0.01) in the laparoscopic group and by 20% (1.97 +/- 0.15%/day vs. 1.57 +/- 0.15%/day, p < 0.01) in the open cholecystectomy group. In contrast, the fall in insulin sensitivity after surgery was lower with laparoscopic (22 +/- 2%) compared with open surgery (49 +/- 5%). CONCLUSIONS: Laparoscopic cholecystectomy did not avoid a substantial decline in muscle protein synthesis, despite improved insulin sensitivity. The change in the two parameters occurred independently, indicating different mechanisms controlling insulin sensitivity and muscle protein synthesis.

Adult↗
PubMed1995

Elective abdominal operations alter the free amino acid content of the human intestinal mucosa.

OBJECTIVE: To assess the impact of a standard moderately severe surgical operation on the mucosal amino acid content of the duodenum and the colon. DESIGN: Open study. SETTING: University hospital, Sweden. SUBJECTS: Nine patients who were to undergo elective open cholecystectomy. INTERVENTIONS: Endoscopically obtained biopsy specimens from the intestinal mucosa. MAIN OUTCOME MEASURES: Changes in the content of free amino acids in the duodenum and colon at three days postoperatively. RESULTS: The concentration of glutamine in the duodenum increased by 27% and that of glutamic acid by 34% after operation, whereas their content in colon remained unaltered. The concentration of branched chain amino acids increased by 26% in the duodenal mucosa after operation and by 24% in the colonic mucosa. The total concentration of amino acids (excluding taurine) increased by 9% in the duodenum, but remained unaltered in the colon. CONCLUSION: This study shows characteristic and consistent alterations in the free amino acid content of the intestinal tract after a moderately severe operation.

Amino Acids↗
PubMed1994

Long-term effects of postoperative total parenteral nutrition supplemented with glycylglutamine on subjective fatigue and muscle protein synthesis.

Seventeen patients undergoing elective open cholecystectomy were given conventional total parenteral nutrition either with (nine patients) or without (eight) glutamine supplementation of 20 g/day for 3 days after surgery and thereafter ordinary food for the following 27 days. Muscle protein synthesis, as assessed by the total concentration of ribosomes, decreased in control patients on day 3 following surgery and remained low on days 10, 20 and 30 (P < 0.05). In patients who received glutamine the total ribosome concentration was maintained on the third day after operation. Concurrently, the subjective feeling of fatigue increased on days 3 and 10 after surgery and the nitrogen balance was negative after operation in both groups, without any difference related to glutamine supplementation. Intravenous glutamine after surgery counteracts a decline in muscle protein synthesis only for as long as it is provided.

Cholecystectomy↗
PubMed1994

Stress hormone and amino acid infusion in healthy volunteers: short-term effects on protein synthesis and amino acid metabolism in skeletal muscle.

To study the immediate effects of stress hormones and intravenous amino acid support, healthy male volunteers were administered a stress-hormone infusion including epinephrine, cortisol, and glucagon either alone (Triple, n = 8) or combined with a balanced glutamine-free amino acid solution (Triple AA, n = 8) over a period of 6 hours. The amino acid infusion was started 2 hours after the hormone infusion. A third group (AA, n = 8) received the balanced amino acid solution alone. After 6 hours of the stress-hormone infusion, a decrease was observed in skeletal muscle protein synthesis as measured by the size distribution and concentration of ribosomes. The decrease was prevented by an infusion of the balanced amino acid solution. Following the triple-hormone infusion, a decrease was noted in the content of the total free amino acids in both muscle and plasma. After including amino acids in the infusion solution, the significant decrease in muscle glutamine caused by the triple hormones was not seen. Plasma cortisol, insulin, and glucose increased in response to the triple-hormone infusion alone or in combination with amino acids. In summary, the results show that the signs of muscle protein catabolism elicited by administration of stress hormones can be attenuated by simultaneous administration of a conventional amino acid solution, although it does not contain glutamine.

Adult↗
PubMed1994

Short-term starvation alters the free amino acid content of the human intestinal mucosa.

1. The effects of short-term starvation and refeeding on the free amino acid concentrations of the intestinal mucosa were characterized in male subjects (n = 6), using endoscopically obtained biopsy specimens from the duodenum and from all four segments of the colon. 2. The alterations in the amino acid concentrations in response to short-term starvation were overall uniform in both duodenal and colonic mucosa as well as in plasma. Most amino acids decreased, whereas branched-chain amino acids increased. 3. In the colon, glutamic acid and glutamine decreased during the starvation period, whereas they remained unaltered in the duodenum. This was the major difference in response to short-term starvation between the amino acid concentrations in the intestinal mucosa of the duodenum and colon. 4. Refeeding for 3 days normalized the amino acid concentrations except for glutamic acid, asparagine and histidine, which remained low in the colon, and threonine, which showed an overshoot in both parts of the intestine. 5. The changes in mucosal amino acid concentrations seen in response to starvation and refeeding were uniform in the four segments of the colon. This suggests that sampling from the rectum/sigmoid colon will give representative values for the free amino acid concentrations of the entire large intestine.

Adult↗
PubMed1994

The separate and combined effect of leucine and insulin on muscle free amino acids.

The effect of insulin and leucine on amino acid and protein metabolism in muscle is not fully understood. To characterize their separate and combined effects on free amino acids in muscle and plasma, 11 volunteers received an infusion of either leucine (1 g h-1, Group 1) or glucose (20 g h-1, Group 2) for 2 h followed by a combination of the two infusions for an additional 2-h period. In muscle both the leucine infusion and the leucine plus glucose infusion increased the concentration of free leucine significantly, while the sum of the other branched chain amino acids (BCAA), of the aromatic amino acids and of the basic amino acids decreased. Glucose infusion alone decreased the sum of the essential amino acids, the BCAA and the aromatic amino acids. The combination of leucine and glucose augmented the decreases, while the concentrations of glutamate, glutamine and alanine were unaffected. In plasma the leucine infusion doubled the leucine concentration and decreased alanine, valine, methionine, tyrosine, phenylalanine and the sum of the aromatic amino acids. Glucose infusion decreased methionine, serine, isoleucine and the sum of the essential amino acids and of the BCAA. The combination of leucine infusion and hyperinsulinaemia augmented the decreases. The plasma concentrations of the keto acids of valine and isoleucine decreased by the leucine infusion while the concentrations of the keto acid of leucine and isoleucine decreased by glucose infusion. The combination of leucine and glucose had an additive effect. These effects are attributed to a specific effect of leucine on the other two BCAA and a depression of muscle proteolysis by both leucine and insulin, resulting from glucose infusion.

Adult↗
PubMed1994

Measurement of tissue protein synthesis rates in vivo: a critical analysis of contrasting methods.

The extension of the flooding method for measuring the rate of protein synthesis, from animal to human tissues, has led to criticism. This is based on the observation that in human muscle, unlike animal tissues, the rate of synthesis in the fasting state measured with constant infusion is lower than that obtained with the flooding technique. Moreover, incorporation of infused tracer can be enhanced with a simultaneous flood, although an inhibition of incorporation has also been reported. Explanations for these observed discrepancies are explored. Evidence from studies in human muscle both with flooding and with a nonisotopic technique have given no indication of a stimulation of protein synthesis during flooding. It is therefore concluded that the most likely explanation for the discrepancy between methods is that changes in the isotopic enrichment of the precursor amino acid, which are minimized by the flooding procedure, are not adequately accounted for with the constant infusion method.

Animals↗
PubMed1993

Free amino acids in biopsy specimens from the human colonic mucosa.

The content of free amino acids and total protein was determined in endoscopic biopsy specimens from the rectum, descending colon, transverse colon, and ascending colon in 10 patients. The amino acids were quantified by ion-exchange chromatography and were detected by fluorescence. The amino acid pattern and the rank order of the individual amino acids in the colon were different compared to those in plasma. Glutamate, taurine, aspartate, glutamine, glycine, alanine, serine, lysine, valine, and ornithine were the 10 most abundant amino acids in the colon. The rank order was the same in all of the different segments of the colon. The concentrations of the amino acids decreased the more aborally the biopsies were taken. The protein content in the rectum was significantly lower than that in the transverse colon, but there were no difference between the different segments otherwise. The study demonstrated the possibility of determining free amino acids from endoscopic biopsies of human colonic mucosa. Biopsy specimens from the descending colon and/or rectum/sigmoid colon may be considered representative of the entire large intestine. The technique may be used for repeated sampling in studies of the amino acid metabolism of the intestinal mucosa.

Aged↗
PubMed1993

The content of free amino acids in the human duodenal mucosa.

The free amino acid concentrations and the total protein content of the duodenal mucosa were determined in biopsy specimens obtained during endoscopic examinations in 10 healthy subjects. The amino acids were separated and quantified by ion exchange chromatography using fluorescence detection. The protein content was analysed according to Lowry. The amino acid pattern found in the duodenal mucosa was quite different from that in the plasma. The total amounts of all individual free amino acids were considerably higher in the mucosa than in the plasma (16.2 +/- 0.6 mmol/kg biopsy weight compared to 2.4 +/- 0.1 mmol/l). Taurine, glutamate and aspartate constituted more then 65% of the total content of all amino acids in the mucosa. Glutamine, the most abundant amino acid in plasma (21%), ranked only as sixth in the duodenal mucosa (4%); still, the absolute concentrations were quite similar in the mucosa and plasma (0.60 +/- 0.05 mmol/kg vs. 0.53 +/- 0.02 mmol/l). This study demonstrates the possibility of determining free amino acids in endoscopic biopsy specimens from the human duodenum. The technique is recommended for repeated sampling in clinical studies on the amino acid metabolism of the intestinal mucosa.

Journal Article↗
PubMed1993

Temporal responses of protein synthesis in human skeletal muscle to feeding.

In attempting to evaluate alterations in metabolic responses to dietary nutrients that occur in pathological conditions in man, it is first necessary to understand normal metabolic responses. The present study set out to determine the temporal responses of protein synthesis in the skeletal muscle of healthy subjects to the consumption of food. Sequential measurements of protein synthesis in quadriceps muscle were made in eight subjects by injection of 0.05 g L-[1-13C]leucine/kg body-weight. The rate of protein synthesis after an overnight fast (i.e. in the post-absorptive state) was 2.2% muscle protein. After 1 h of eating, protein synthesis was unaltered (2.2%/d), but after 10 h of consuming small hourly meals the rate had risen to 2.9%/d, with a variation in response among individuals. The response of muscle to 10 h of feeding was also investigated in subjects who underwent only one measurement each, either after 10 h of eating small meals or after the same time-period when no food was given. Protein synthesis rates were only slightly elevated in the group of fed individuals (2.3%/d, n 6) compared with the fasted group (2.1%/d, n 6). Taken together the two studies suggest that in healthy adults muscle protein synthesis does not respond quickly to the influx of dietary nutrients and that even after 10 h of feeding any stimulation of protein synthesis is small.

Adult↗
PubMed1993

Stress hormones alter the pattern of free amino acids in human skeletal muscle.

Stress hormones were infused for 6 h in healthy volunteers (n = 32). Free amino acid concentrations were determined in plasma and in skeletal muscle biopsy specimens. A triple hormone combination of adrenaline, cortisol, and glucagon raised the level of alanine in muscle, while glutamine, glutamate, the branched chain amino acids, the aromatic amino acids, and the basic amino acids decreased. Adrenaline alone partly reproduced this pattern, while a 6-h infusion of cortisol left the muscle free amino acids unaffected. In plasma all individual amino acids except alanine and glutamate decreased in the subjects receiving adrenaline or a triple-hormone combination. Altered plasma amino acid concentrations did not necessarily reflect changes in the tissue amino acid content. It is concluded that an infusion of a triple combination of stress hormones into healthy volunteers produces changes in muscle amino acid metabolism similar to those seen immediately after surgical trauma.

Adult↗
PubMed1993

Muscle protein synthesis after operation: effects of intravenous nutrition.

OBJECTIVE: To assess the effect of an elective abdominal surgical operation (open cholecystectomy) on the rate of protein synthesis in skeletal muscle in humans. DESIGN: Prospective random control trial. SETTING: University hospital. SUBJECTS: 17 Metabolically healthy patients who were to undergo elective open cholecystectomy. INTERVENTIONS: Patients randomised to receive either saline alone (n = 8) or total parenteral nutrition (n = 9) for three days after operation. The rate of protein synthesis in muscle was calculated from the increase in enrichment of (1-13C) leucine in protein after a flooding dose of (1-13C) leucine. RESULTS: Median (quartiles) rate of protein synthesis had decreased on the third postoperative day in the saline group by 49% (from 2.42 [2.03, 2.54] to 1.24 [0.99, 1.63]) and in the group that had received total parenteral nutrition by 54% (from 1.96 [1.90, 2.07] to 0.91 [0.79, 1.06]) (p < 0.01). CONCLUSIONS: The trauma associated with open cholecystectomy reduced the rate of protein synthesis in skeletal muscle by half in three days, and conventional total parenteral nutrition had no effect on these changes.

Adult↗
PubMed1993

Effect of growth hormone on muscle and protein in critically ill patients.

In summary, the effects of protein metabolism of the provision of additional GH are well documented in critically ill patients. Nitrogen balance improves as urea production is diminished. The crucial question is whether this lowers the availability of glutamine for cells dependent on it in critical illness. In parallel, muscle protein synthesis is stimulated by GH and the free glutamine content of muscle is maintained in situations when a depletion of muscle glutamine is otherwise seen. Another consistent finding in most clinical studies is the pronounced interindividual variability in the response to GH. So far, no marker has been identified to predict an individual patient's sensitivity to GH, but the identification of individuals who are likely to benefit from GH treatment during critical illness should be a priority in future clinical research on GH.

Animals↗