Digestion and absorption of dietary protein in man.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to D B Silk.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Because of the generally more rapid amino acid absorption and lower osmotic pressure of small peptides compared with free amino acids, it has been suggested that 'elemental' diets should contain both small peptides and free amino acids as the nitrogen source. While studying protein hydrolysates intended for use in such diets we observed surprising differences in the absorption of amino acids, water, and Na+ during jejunal perfusion of partial enzymic hydrolysates of two proteins (lactalbumin and fish) which contained high and approximately equal amounts of their constituent amino acids in the form of small peptides. Total alpha amino nitrogen (alpha NH2N) absorption from the lactalbumin hydrolysate was greater, and individual amino acid absorption more even, than from equinitrogenous solutions of the fish protein hydrolysate, or from mixture of free amino acids simulating either hydrolysate. Net water and Na+ absorption occurred during perfusion of the lactalbumin hydrolysate, whereas net water and Na+ secretion occurred during perfusion of the fish protein hydrolysate. These differences were significant (P < 0.05 or less). As the differences between the hydrolysates are so marked, we conclude that it is unwise to assume that all protein hydrolysates are equally suitable for use in patients.
Cerebral oedema is the commonest immediate cause of death in fulminant hepatic failure and an investigation was carried out to determine the value of monitoring intracranial pressure (ICP) and to examine the effects of ICP of dexamethasone therapy and mannitol administration. ICP values in 10 patients at the time of insertion of a subdural pressure transducer (grade IV encephalopathy) averaged 15.5 +/- SD 14.8 mmHg. Despite dexamethansone therapy, which had been started on admission, rises in ICP were subsequently observed in seven of the eight patients who died. In the two patients who survived, the highest reading were 47 and 35 mmHg. Mannitol consistently reversed or arrested ICP rises when pressure was < 60 mmHg. ICP monitoring provides additional information in the managment of patients and is essential if mannitol therapy is to be used.
To compare the efficacy of two oesophageal tamponade tubes, 28 patients with endoscopically proven actively bleeding varices were randomly allocated to be intubated with either a newly available 4-lumen tube incorporating an extra lumen for oesophageal suction, or the modified 3-lumen Sengstaken tube. The patients and the nursing staff preferred using the 4-lumen tube and both aspiration pneumonias and balloon dysfunction occurred less frequently. Variceal haemorrhage was successfully controlled for the first 12 hours in most patients in the two treatment groups, although the incidence of re-bleeding at 48 hours after the tube had been deflated was high.
In the present study the conditions leading to tight binding of human serum albumin to the Amberlite XAD-7 resin without the use of chemical coupling agents have been defined. Optimal binding (10.97 mm/kg dry XAD-7) was achieved at pH 5.0 and adsorption conformed to a Langmuir isotherm. Theoretical analysis of the data suggest adsorption of a monolayer of albumin which is supported by the absence of visual surface coating on scanning electron micrographs. Binding of human serum albumin was reduced when two chemical coupling agents, glutaraldehyde and carbodiimide were included in the human serum albumin solution, the elution of adsorbed HSA from the resins under severe flow conditions was reduced, and the amount eluted was minimal in all instances.
Explore the source record for details and available documents.
Platelets adhere to most foreign surfaces. As a result, polymers and albumin have been suggested as possible coatings to improve the blood compatibility of such surfaces. Amberlite XAD-7 has a high affinity for human serum albumin (HSA) and several protein-bound toxic metabolites. In the present study it is shown that HSA can be tightly bound to Amberlite XAD-7 without the use of chemical coupling agents. Optimal binding was achieved at pH 5.0 and the adsorption conforms to Langmuir's isotherm. Theoretical analysis of data and absence of a residual surface coating visible with scanning electron microscopy suggest a monolayer of albumin. The amount of HSA eluted from the resin under severe flow conditions was negligible (approximately 1%). Furthermore, in stirred batch studies with human plasma, the HSA coating did not decrease the adsorptive capacity of XAD-7 for bile acids and bilirubin.
Albumin-coated Amberlite XAD-7 has been previously shown to be blood compatible in in vitro hemoperfusion experiments whith human blood. In this study, the preliminary results are reported on single hemoperfusions with albumin-coated XAD-7 resin in four patients with acute liver failure. The mean platelet count was 116+/-SE 16.3% of the initial arterial value and the mean white cell count was 96+/-SE 6.5% of initial at the end of four hours of hemoperfusion. Removal of bilirubin, phenols and substances in the middle molecular weight range by the resin was demonstrated. These preliminary results suggest albumin-coated Amberlite XAD-7 resin to be blood compatible and capable of removing protein-bound and middle molecular weight substances from patients with acute liver failure. Further clinical evaluation of repeated resin hemoperfusion is required to determine whether this treatment will be beneficial to patient survival.
Intestinal perfusion studies performed in man have suggested that amino acid nitrogen may be absorbed more rapidly from peptides than free amino acids. The aim of the present study was to compare the effects of the oral administration of peptides and free amino acids. Two isonitrogenous liquid test meals, one containing 50 g of a partial enzymic hydrolysate of fish protein in which approximately 80% of the nitrogen content was present as small peptides (peptide meal), and the other a mixture of free amino acids (amino acid meal) the composition and molar pattern of which simulated that of the peptide meal, were administered on separate occasions to six normal subjects intubated with a triple lumen tube. Both meals contained the reference marker polyethylene glycol. Fractional absorption of amino acid residues one and two hours after ingestion of the two meals was similar at three intestinal locations situated 120, 160, and 200 cm from the mouth of each subject, and at two hours 73.8% and 72.0% of the amino acid residues had been absorbed respectively by the time the contents of the peptide and amino acid meals reached the middle sampling port of the tube. The total sum of individual amino acid increments in plasma was significantly greater 30 minutes (p < 0.025) and one hour (p < 0.05) after ingestion of the peptide than amino acid meals. By three hours the total area under the two plasma curves was similar. Normal human subjects thus appeared to be capable of assimilating orally administered mixtures of peptides and free amino acids with equal efficiency. Secretion of fluid into the lumen of the upper small intestine, assessed by reference to dilution of the polyethylene glycol, was less after ingestion of the peptide meal. In clinical situations characterised by fluid and electrolyte malabsorption consideration might be given to using small peptides rather than free amino acids as the nitrogen source in nutritional diets.
In previous studies severe side effects, including irreversible hypotension, platelet losses and rises in Swank screen filtration pressure, have been recorded during the treatment by charcoal haemoperfusion of patients with fulminant hepatic failure. It has also been demonstrated that rises in Swank screen filtration pressure in an in vitro test circuit are due to the presence of platelet aggregates. In this study Prostacyclin was infused at a constant rate, to give a blood concentration of 5 ng/ml, into the in vitro circuit just prior to the charcoal column. Rises in Swank screen filtration pressure were prevented, and it was also shown that the giving of a bolus dose of Prostacyclin (400 ng/ml blood concentration) reversed rises in Swank screen filtration pressure that have already occurred. On the basis of these findings, Prostacyclin would be expected to be of considerable clinical value in the prevention of adverse platelet reactions to charcoal haemoperfusion when carried out in patients with fulminant hepatic failure.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Cerebral edema has now been noted to occur frequently in patients dying of fulminant hepatic failure. In the present study, intracranial pressure was monitored in an animal model of acute liver failure. Acute liver failure was induced surgically by hepatic devascularization. Serial monitoring of the electroencephalogram revealed progressive slowing of the frequency with decreasing amplitude. Elevation of the blood ammonia was also observed from baseline values of 64 +/- 12 SE to 744 +/- 97 mumol/liter. Monitoring of the intracranial pressure with a subdural pressure transducer demonstrated a progressive and reproducible rise from 12.8 +/- 2.5 mm Hg immediately after the operation to a mean value of 51.6 +/- 11.8 mm Hg just before death 6--12 hr later. At autopsy, the brains of the test animals were found to be swollen with flattened cortical gyri. In the control animals, intracranial pressure rose slightly but returned toward normal levels (8.0 +/- 2.5 mm Hg) 8 hr after laparotomy and remained normal until their death. There was a statistically significant difference between intracranial pressure levels of the test animals and those of the controls (P less than 0.01). Intravenous methylprednisolone (2.0 g initially followed by 0.5 g every 2 hr) administered immediately before and after hepatic devascularization prevented rises in intracranial pressure but had no effect when given 4 hr after operation. The early and progressive increase in intracranial pressure was an unexpected finding, and an assessment of such a sequence in patients with fulminant hepatic failure is currently in progress.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
1. A randomly labelled 14C protein was synthesized in order to investigate the site and rate of digestion and absorption of dietary protein in the rat. 2. A liquid test meal consisting of protein and a non-absorbable marker, 51CrCl3, was administered to rats which were then sacrificed at intervals up to 4 hr after ingestion of the meal. Analysis of intestinal contents showed that as gastric emptying proceeded, the meal moved rapidly to the distal two thirds of the small intestine. 3. Protein digestion and absorption occurred predominantly in this area over a period of 1-2 hr. 4. Amounts of endogenous protein present in the small intestine never exceeded amounts of exogenous protein during maximum absorption of exogenous protein (0-1 hr). At later time periods (2-4 hr), however, more endogenous than exogenous protein was detected in the intestinal lumen. 5. It is concluded that the digestion and absorption of dietary protein is a rapid process, taking place in the distal two-thirds of the small intestine. Endogenous protein levels do not exceed exogenous protein levels until after the bulk of exogeneous protein is absorbed.
An intestinal perfusion technique has been used to study absorption of glucose from free glucose and the disacchairde maltose in a patient with congenital glucose-galactose malabsorption. Minimal absorption of glucose occurred from high luminal concentrations of either free glucose (100 mmole/liter) or maltose (50 mmole/liter). Glucose diffused into the intestinal lumen during perfusion of a 2 mmole/liter glucose solution. These observations offer no support for nutritionally important glucose absorption in congenital glucose-galactose malabsorption by either passive diffusion or via a "disaccharidase-related" transport system.