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P Pedersen

Publications and source records attributed to P Pedersen.

At least 55 records · Page 3Linked to original sources
PubMed1988

Current concepts of protein turnover and amino acid transport in liver and skeletal muscle during sepsis.

The metabolic response to trauma and sepsis is characterized by a negative nitrogen balance, accelerated muscle proteolysis, increased ureagenesis, and stimulated acute-phase protein synthesis in liver. Inhibited uptake of amino acids and accelerated protein breakdown in muscle increase the flux of amino acids from the periphery to the liver. Concomitantly, hepatic uptake of amino acids is stimulated and protein synthesis and gluconeogenesis in the liver are enhanced. These events are important to the survival of patients with sepsis. Stimulated ureagenesis resulting in nitrogen loss from the body is another important aspect of hepatic nitrogen metabolism following trauma and sepsis. The mediator(s) initiating metabolic changes is not yet exactly defined, although regulatory protein(s) released from stimulated macrophages (particularly interleukin 1 and tumor necrosis factor) may play a major role in altered amino acid and protein metabolism in muscle and liver during sepsis. However, these factors alone are probably not responsible for the metabolic disturbances, since the catabolic hormones cortisol, glucagon, and the catecholamines can simulate the metabolic pattern observed in sepsis. Other possible mediators include prostaglandins and thyroid hormones. It is possible that the interaction between different types of mediators is necessary for the full manifestation of host responses to severe injury and sepsis.

Amino Acids↗
PubMed1988

Synthesis of acute-phase proteins in perfused liver following administration of recombinant interleukin 1 alpha to normal or adrenalectomized rats.

The purpose of this study was to investigate the effects of recombinant interleukin 1 alpha (rIL-1 alpha) on metabolic rate and synthesis of acute-phase proteins in intact and adrenalectomized rats. Animals were housed in metabolic cages with daily recording of food intake and body weight. Twice daily, for 3 days, the rats were injected intraperitoneally with 5000 LAF U of human rIL-1 alpha, purified from Escherichia coli. Control animals were pair-fed and received corresponding injections with saline. In the morning of the fourth day, resting energy expenditure (REE) was determined by indirect calorimetry, and synthesis of total secreted proteins, albumin, complement component C3, and seromucoid fraction was measured by radioimmunological method using rat-specific antisera and [3H]leucine in livers perfused for 2 hr. Food intake decreased by approximately 30% during rIL-1 alpha administration to intact rats. The decrease in food intake occurred later and was less pronounced in adrenalectomized rats receiving rIL-1 alpha. Growth rate was significantly reduced on the first day of rIL-1 alpha treatment in intact rats, while there was no effect on growth rate in adrenalectomized animals. After rIL-1 alpha administration, REE was increased by 26% in intact rats (P less than 0.001) and by 14% in adrenalectomized rats (N.S.). Increased synthesis rates of total secreted proteins, complement component C3, and seromucoid fraction were observed in livers of intact rats following rIL-1 alpha administration. In adrenalectomized rats, only production of C3 was significantly increased after treatment with rIL-1 alpha. Albumin synthesis rate was not changed in either group following rIL-1 alpha injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Proteins↗
PubMed1988

Methods for studying protein synthesis and degradation in liver and skeletal muscle.

Different methods used for measuring protein turnover in liver and skeletal muscle are described, with special emphasis on technical and practical aspects and the advantages and limitations of different techniques. In the first part of the review, the concept of precursor specific radioactivity and its importance for accurate determination of protein synthesis rate is discussed. In the second part, different in vivo techniques for protein turnover measurements are reviewed, including continuous administration of tracer amino acid, flooding dose technique, indirect measurement of protein synthesis, and estimation of protein degradation in vivo. In the third part of the report, in vitro techniques are described, including measurement of protein turnover in incubated liver slices, perfused liver, isolated hepatocytes, incubated isolated muscles or muscle biopsies, and perfused rat hemicorpus. In vivo techniques are preferred when accurate absolute values of protein turnover rates are desired. In vitro techniques offer the advantage of standardized conditions, maintaining strict control of substrate and hormone concentrations, and eliminating complicating interactions with other tissues. For several in vitro techniques, a good correlation has been demonstrated between relative changes in protein turnover in vitro and in vivo in different conditions.

Animals↗
PubMed1988

Administration of balanced or BCAA-enriched amino acid solution in septic rats. Effects on protein synthesis in the liver.

Total hepatic protein synthesis was measured in vivo with a flooding-dose technique, and the production of total secreted proteins, albumin, complement component C3, and seromucoid fraction was measured in perfused livers of septic rats that received one of three different solutions infused intravenously; Group 1 received 16.4% dextrose; Group 2 received Aminosyn (25% BCAA) in 10.6% dextrose, and Group 3 received Freamine HBC (45% BCAA) in 10.6% dextrose. All solutions were isocaloric, and the amino acid solutions were isonitrogenous. The solutions were administered for 18 or 48 hours after the induction of sepsis. There were no significant differences in mortality rates in the three treatment groups. The negative nitrogen balance seen in the dextrose-infused animals was reversed to the same degree by the two different amino acid solutions. There were no significant differences in hepatic protein synthesis rates in vivo between the three groups of rats. Synthesis rates of secreted proteins in perfused liver were similar in the different treatment groups in the 18-hour experiments, whereas in the 48-hour experiments, synthesis rates of total secreted proteins, C3, and the serumucoid fraction were higher in Group 1 than in Groups 2 and 3. The results suggest that administration of an amino acid solution improves nitrogen balance in sepsis, but that this effect is not caused by stimulated hepatic protein synthesis. The nitrogen-sparing effect during sepsis of a branched chain amino acid (BCAA)-enriched solution does not seem to be superior to that of a balanced amino acid solution.

Amino Acids↗
PubMed1988

The use of indomethacin to prevent the formation of heterotopic bone after total hip replacement. A randomized, double-blind clinical trial.

We studied the effect of indomethacin on the prevention of formation of heterotopic bone after total hip replacement. In a randomized, double-blind clinical trial involving 201 patients, 102 patients received twenty-five milligrams of indomethacin three times daily for the first six postoperative weeks, and the other ninety-nine patients received a placebo. One year after the operation, eighty-nine of those who had received indomethacin had no sign of heterotopic ossification, and the remaining thirteen had a grade-I lesion. In the group that had received a placebo, twenty-seven had no heterotopic ossification; twenty-four, a grade-I lesion; thirty, a grade-II lesion; and eighteen, a grade-III lesion. Significantly fewer patients who had received indomethacin had formation of heterotopic bone compared with those who had been given a placebo (chi-square test, p less than 0.0005). Only patients who had grade-III formation of heterotopic bone had a significant reduction in movement of the hip.

Adult↗
PubMed1988

Serum alkaline phosphatase as an indicator of heterotopic bone formation following total hip arthroplasty.

Serum alkaline phosphatase (SAP) was analyzed in 193 patients treated with total hip arthroplasty (THA) and correlated with the degree of heterotopic bone formation (HBF) one year after surgery. The influence of indomethacin on changes in SAP related to the development of heterotopic bone was studied. Ninety-eight patients received 25 mg of indomethacin three times daily for the first six postoperative weeks; the remaining 95 patients received a placebo treatment. No further anti-inflammatory drugs were allowed during the six weeks. SAP was measured preoperatively and six weeks and 12 weeks after surgery. No patients at risk for developing heterotopic bone after THA could be identified from the preoperative level of SAP. The level of SAP six weeks after THA gradually increased with the amount of HBF. A rise in SAP above 250 IU/liter 12 weeks after surgery was associated with the development of severe heterotopic bone in 13 of 17 patients. Indomethacin inhibited the development of heterotopic bone associated with a rise in SAP following THA. Future studies on HBF and SAP following THA should include information on patient use of anti-inflammatory drugs in the early postoperative period.

Adult↗
PubMed1987

The cystic fibrosis locus.

The identification of the cystic fibrosis locus (CF) provides a model for the study of single gene defects where the biochemical lesion is not known. Using families each of which has several affected siblings, it was possible to exclude a number of 'candidate genes' which had previously been proposed as possible sites of the CF mutation. Exclusion mapping of the genome using polymorphic protein and DNA markers showed that CF is on the long arm of human chromosome 7. The most closely linked flanking markers were identified, and human chromosome fragments containing them (and therefore the CF locus) were isolated in rodent cell lines by chromosome-mediated gene transfer. The transgenome was then analysed using cosmid contig mapping, pulse-field gel electrophoresis, HTF island identification and linkage disequilibrium. In this way, a candidate coding sequence has been identified which always segregates with CF.

Animals↗
PubMed1987

Protein and energy metabolism in liver tissue following intravenous infusion of live E. coli bacteria in rats.

In the present study protein synthesis and energy level in liver tissue were studied in bacteremic rats following intravenous infusion of 8 +/- 4 X 10(9) live E. coli bacteria and in control animals receiving a corresponding infusion of sterile saline. For the study of protein synthesis, liver slices were incubated in a medium containing 14C-leucine and incorporation rate of amino acid into protein was determined. Hepatic concentrations of ATP, ADP, and AMP were measured and energy charge (EC) was calculated. Twenty-four hours after infusion of E. coli, hepatic protein synthesis rate was 55% higher than in control animals. Liver weight and hepatic protein content were also increased in bacteremic animals. There were no significant differences in adenine nucleotide levels or EC in liver tissue between control and bacteremic animals. Since impairment of various other liver functions has been reported during sepsis, the present results suggest that hepatic protein synthesis has high priority in this condition.

Adenine Nucleotides↗
PubMed1986

Protein synthesis and degradation in liver tissue following induction of septic peritonitis in rats.

Protein synthesis and degradation in liver tissue were studied in rats following induction of septic peritonitis by ligation and puncture of the cecum. Protein synthesis was studied by determining the rate of leucine incorporation into protein in incubated liver slices. Protein degradation was measured in vitro as release of trichloroacetic acid soluble radioactivity from protein prelabelled with 14C-leucine and in vivo from decay of radioactivity in hepatic protein labelled with 14C-sodium bicarbonate. Measurements 24 hours after induction of septic peritonitis showed increase in liver weight and total hepatic protein content. Protein synthesis was higher in rats with septic peritonitis than in control rats 12 and 24 hours after cecal ligation and puncture. Protein degradation was unchanged. The results support the concept that net production of hepatic protein is increased in septic peritonitis, due to accelerated synthesis and unchanged degradation. Since other hepatocellular functions were previously reported to be depressed in the same experimental model, the present results indicate that hepatic protein synthesis has high priority during sepsis.

Animals↗
PubMed1984

Changes of protein metabolism in liver and skeletal muscle following trauma complicated by sepsis.

The effects of trauma (laparotomy) and trauma complicated by sepsis (laparotomy and ligation and puncture of the cecum) on protein metabolism in liver and skeletal muscle were studied in rats. Unoperated animals served as controls. Rate of amino acid incorporation into proteins was determined in incubated liver slices and bundles of muscle fibers. Proteolysis in skeletal muscle was measured as release of tyrosine from incubated muscle biopsies. Protein synthesis in liver tissue was increased by 42% following trauma and by 164% following trauma and sepsis. In skeletal muscle amino acid incorporation into proteins was reduced by 50% in both conditions while protein degradation was enhanced by about 70%. Thus when injury was complicated by sepsis the metabolic response was augmented in liver but not in skeletal muscle. One reason for this difference might be that changes of protein metabolism in trauma and sepsis are regulated by different mechanisms in liver and skeletal muscle. The results also indicate that increased amino acid supply from peripheral protein breakdown is not the only signal for enhanced hepatic protein synthesis in trauma and sepsis.

Amino Acids↗
PubMed1984

Hemodynamic and hematologic changes in a standardized trauma-sepsis model in rats.

The aim of this report was to describe an experimental trauma-sepsis model in rats. Trauma consisted of laparotomy and sepsis was induced by intravenous infusion of different amounts (10(8)-10(10)) of live Escherichia coli. Three experimental series were performed. In the first series survival rates were studied up to 7 days after trauma-sepsis. In the second and third series pulse rate, intraarterial blood pressure, cardiac output, liver blood flow and hematologic changes were studied after 24 h. Cardiac output was determined by dye-dilution method and hepatic blood flow by 133Xe wash-out technique. Survival rates were decreased in a dose-related manner when the amount of bacteria administered was increased from 10(8) to 10(10). Twenty-four hours after trauma-sepsis, survival rate was 100% following E. coli 10(8), 69% following E. coli 10(9), and 23% following E. coli 10(10). After 7 days the corresponding figures were 85%, 31%, and 8%. A dose-related decrease was also observed for cardiac output and hepatic blood flow when the amount of bacteria was increased. Mean arterial blood pressure was unchanged. Platelet and white blood cell counts were reduced 24 h following trauma-sepsis, and these changes were also more pronounced when the amount of bacteria infused was increased. Thus, it was possible to demonstrate a graded response following increasing amounts of bacteria regarding survival rate, cardiac output, liver blood flow, and hematologic changes in three subsequent experimental series. A carefully standardized experimental model may be of value for studies of metabolic events following trauma and sepsis.

Animals↗
PubMed1983

A new distending laryngoscope for diagnosis and microsurgery of the larynx.

A new laryngoscope was developed in order to improve visualization of the larynx and to better adapt the instrument to individual clinical circumstances. As such, the Kleinsasser laryngoscope was divided into two parts, with the width between the two halves changed by adjustment of a screw. The lower part of the instrument can also be moved to provide more space near the larynx. Since the laryngoscope is open laterally, there is more space for the operator, and shorter instruments can be used for endolaryngeal manipulations. The endoscope can be used for intubation as well as for injection. With the new instrument the advantages of the Kleinsasser laryngoscope with the Killian suspension endoscope have been combined.

Humans↗