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Biomedical subjects

D B Silk

Publications and source records attributed to D B Silk.

At least 145 records · Page 8Linked to original sources
PubMed1978

The use of an in vitro haemoperfusion circuit to evaluate the blood compatibility of albumin-coated Amberlite XAD-7 resin.

We have developed an in vitro haemoperfusion circuit, which closely simulates the conditions encountered in a clinical haemoperfusion, for testing the blood compatibility of new adsorbent materials. Fresh heparinised human blood is perfused for 2 hours over two model columns arranged in parallel closed circuits. The present study was performed to investigate the blood compatibility of human serum albumin-coated Amberlite XAD-7 resin. Mean platelet losses over 2 hours were greater following perfusion of the uncoated resin (44 +/- SE 5.6%) than the albumin-coated resin (17 +/- SE 2.2%) (p less than 0.01). Mean white cell losses were similar (55%) for both resins. No rises in Swank screen filtration pressure, which detects the presence of cellular aggregates in blood, were observed. Coating of XAD-7 resin with HSA therefore improves its blood compatibility with respect to platelet losses and we thus intend to use this preparation in a clinical trial of resin haemoperfusion in fulminant hepatic failure.

Acrylic Resins↗
PubMed1977

Plasma short-chain fatty acids in fulminant hepatic failure.

The role of short-chain fatty acids in the pathogenesis of coma in patients with fulminant hepatic failure has been studied by gas-liquid chromatography. There was no correlation between the initial or the final plasma levels of short-chain fatty acids in these patients and the clinical outcome of their disease. A primary role for the short-chain fatty acids in the pathogenesis of coma in fulminant hepatic failure is unlikely.

Acetaminophen↗
PubMed1977

Treatment of fulminant hepatic failure by polyacrylonitrile-membrane haemodialysis.

24 patients with fulminant hepatic failure who had deteriorated to grade-IV coma were treated by repeated periods of haemodialysis with a polyacrylonitrile membrane. 9 patients fully recovered consciousness, and 8 (33%) survived to leave hospitals. These results are to be compared with those of conservative management alone (15% survival in 53 cases) and those obtained initially with charcoal haemo-perfusion (38%). Of the 16 treatment failures, cerebral oedema was found at necropsy in 13 (18%). Whether this would have been less of problem if treatment had been started earlier in the course of the illness remains to be determined.

Acrylonitrile↗
PubMed1977

Effect of glycylglycine on absorption from human jejunum of an amino acid mixture simulating casein and a partial enzymic hydrolysate of casein containing small peptides.

1. A jejunal perfusion technique has been used in normal volunteer subjects to study jejunal absorption of amino acid residues from a partial enzymic hydrolysate of casein in which about 50% of the amino acids existed as small peptides, and also from an equivalent mixture of free amino acids. 2. The effect of a high concentration of the dipeptide glycylglycine on the absorption of amino acid residues from these preparations was studied to quantify the importance of mucosal uptake of intact peptides during absorption of the partial hydrolysate of casein. 3. The results were unexpected. Glycylglycine significantly inhibited absorption of several amino acid residues (aspartic acid + asparagine, serine, glutamic acid + glutamine, proline, alanine, phenylalanine, threonine and isoleucine) from the free amino acid mixture, whereas it significantly inhibited the absorption of only two (serine, glutamin acid + glutamine) from the peptide-containing partial casein hydrolysate. 4. The effect of glycylglycine on absorption of amino acids from the mixture of free amino acids was apparently due to inhibition of amino acid uptake by free glycine liberated from the dipeptide during perfusion. The reason for the failure of glycylglycine to cause extensive inhibition of absorption from the partial hydrolysate is not clear. It may be due to glycylglycine being only a weak inhibitor of peptide uptake, but the possibility that some peptides are taken up by a system unavailable to glycylglycine has to be considered.

Adult↗
PubMed1977

Intestinal lymphoma complicating dermatitis herpetiformis.

A case is reported of a patient with dermatitis herpetiformis who has developed an intestinal lymphoma and a bladder carcinoma during the course of his illness. When considered in conjunction with three recently reported cases it is suggested that intestinal lymphoma may complicate the enteropathy of dermatitis herpetiformis.

Dermatitis Herpetiformis↗
PubMed1977

Serum, cerebrospinal fluid, and brain levels of bile acids in patients with fulminant hepatic failure.

Bile acid levels were measured in the sera, cerebrospinal fluid (CSF), and brain tissue of 10 patients immediately after death from fulminant hepatic (FHF). Serum bile acids in FHF were predominantly conjugated, and total bile acid levels were higher in all 10 patients than in normal controls (85.9 +/- SE 8.4 compared with 5.7 +/- 0.4 nmol/ml, P less than 0.001). Small but significant amounts could be detected in CSF (range 1.2-5.3 nmol total bile acid/ml) and brain biopsies (1.0-18.8 nmol/g wet weight) of FHF patients, whereas none could be detected in CSF and brain biopsies of patients dying without evidence of liver disease. There was no relationship between serum, CSF, or brain levels and duration of coma, or presence of cerebral oedema found in five FHF patients at necropsy. However, serum bile acid levels were similar in FHF to those found in chronic liver disease without encephalopathy and lower than those found to inhibit brain respiration in vitro. A primary role for these compounds in the pathogenesis of coma in FHF therefore seems unlikely.

Adolescent↗
PubMed1977

Affinity chromatography systems for artificial liver support.

The physical, adsorptive, and flow properties of two albumin conjugated agarose materials have been investigated in vitro to determine whether they could be used in artificial liver support systems to enhance the removal of toxic protein-bound substances. The results of binding of chenodeoxycholic acid and unconjugated bilirubin and flow experiments with blood and saline suggested that there could be advantages in using the SepharoseR rather than Bio--GelR albumin agarose in future haemoperfusion systems. However, further modifications are needed before the former can be successfully scaled up for human use.

Chromatography, Affinity↗
PubMed1976

Release of peptide hydrolases during incubation of intact intestinal segments in vitro.

1. Rat intestinal segments have been incubated in isotonic saline in vitro and release of peptide hydrolase enzymes into the incubation media examined over a 90 min study period. 2. Chemical assay data, as well as analysis of electrophoretic mobilities of release enzymes on starch gel, indicate that peptide hydrolase enzymes in the incubation media originate predominantly from the cytoplasm of the mucosal cells. 3. Peptide hydrolases were released rapidly from intact intestinal segments. Release occurred from the start of the in vitro incubations and was not affected by temperature and shaking. 4. It is concluded that compared to the in vivo situation, cytoplasmic peptide hydrolases are released from intestinal tissue very rapidly in vitro. Caution is therefore required when comparing results of in vivo and in vitro peptide absorption experiments.

Animals↗
PubMed1976

Relationships between mucosal hydrolysis and transport of two phenylalanine dipeptides.

In order to investigate the source of free amino acids found in the gut lumen during absorption of dipeptides, as well as evaluating the role of brush border peptidases in the mucosal hydrolysis of dipeptides during absorption, rates of dipeptide disappearance and appearance of hydrolytic products were measured during perfusion of rat jejunum and ileum in vivo with buffered and unbuffered 10 mM solutions of glycl-L-phenylalanine (Gly-Phe) and L-phenylalanyl-glycine (Phe-Gly). Mucosal brush border peptidase activity was then measured in the perfused segments in vitro at luminal pH and at two substrate concentrations. In addition cytosol peptidase activity in the perfused segments was measured at pH 7-4 and at 10 mM substrate concentrations. In the jejunum, there was a relationship between rates of free phenylalanine appearance in vivo (Phe-Gly greater than Gly-Phe) and rates of brush border (Phe-Gly greater than Gly-Phe) rather than cytosol (Gly-Phe greater than Phe-Gly) peptidase activities. No constant relationship between free phenylalanine appearance and hydrolysis of the dipeptides by either brush border or cytosol peptidases was observed in the ileal studies. These findings suggest that, in the jejunum, hydrolytic products originate from the surface of the cell whereas, in the ileum, hydrolytic products originate from both the intracellular compartment as well as from the surface of the mucosal cell. In the jejunum, in vitro rates of brush border hydrolysis of Gly-Phe were always less than in vivo disappearance rates, whereas rates of Phe-Gly brush border hydrolysis always exceeded luminal disappearance rates. These data imply that Gly-Phe is predominantly transported intact and hydrolysed by cytosol peptidases, In contrast, brush border peptidases play an importnat role in the mucosal hydrolysis of Phe-Gly.

Animals↗
PubMed1976

Hydrolysis of peptides within lumen of small intestine.

The quantitative significance of intraluminal peptide hydrolases in the terminal stages of peptide digestion has been investigated, and the precise origins of these enzymes have been determined. Intestinal contents and mucosae were obtained from rats anethetized with ether. Experiments carried out on pancreaticobiliary secretions and germfree rats show that pancreatic and bacterial enzymes do not contribute significantly toward the luminal digestion of dipeptides. Chemical assay data, thermostability studies, and examination of electrophoretic mobilities of luminal peptide hydrolases indicate that jejunal enzymes originate predominantly from the cytoplasm of intestinal mucosal cells, whereas the brush border of muosal cells is a major source of the enzymes in the ileum. With glycl-L-phenylalanine and L-phenylalanyl-glycine as substrates, jejunal luminal activity was less than 2.6% of mucosal activity. Brush-border peptide hydrolase activity in ileal contents, however, was 11.9% and 40.7% of mucosal brush-border activity for the two substrates. Luminal enzymes thus play an insignifcant role in the terminal digestion of peptides in the jejunum, but have a much more important role in the ileal digestion of peptides.

Animals↗
PubMed1975

A study of the renal handling and intestinal absorption of dibasic amino acids in a patient with genotype +/11 heterozygous cystinuria and idiopathic hypercalcuria.

A case is reported of a patient with idiopathic hypercalcuria who was referred for investigation of renal calculi. Studies of urinary amino acid excretion in the patient and all living members of his family, as well as studies of endogenous renal clearances of dibasic amino acids and cystine in the patient and his daughter, indicated that the patient had genotype +/11 heterozygous cystinuria. Intestinal perfusion studies showed however that the patient was able to absorb L-lysine, L-arginine normally from the jejunum and ileum. This suggests that a difference exists between renal and intestinal handling of lysine and arginine in cystinuria.

Adult↗