Biomedical subjects
Publications and source records attributed to T M Chang.
Technetium 99m-DTPA microcapsules have been developed to measure gastric emptying. Such capsules not only provide high labeling efficiency in vitro, but demonstrate limited dissociation in vivo, resulting in decreased error during measurement. In normal control subjects, the half-life ranged from 40 to 80 minutes under the aforementioned conditions.
We investigated the effect of fat or digestive products of fat on the release of endogenous secretin in 15 gastric fistula dogs with either pancreatic fistulas or duodenal fistulas. In 4 dogs with both gastric and duodenal cannulas, intraduodenal administration of corn oil (Lipomul) at a dose of 15 mmol resulted in a significant increase in plasma secretin concentration, whereas in another group of 4 dogs with complete pancreatic duct ligation, the same amount of triglyceride failed to increase the secretin concentration. When Lipomul incubated with pancreatic enzymes was administered in the duodenum, a marked increase in plasma secretin concentration occurred in the 4 dogs with pancreatic duct ligations. In the 7 dogs with chronic pancreatic fistulas, intraduodenal administration of Lipomul resulted in a significant increase in both plasma secretin concentration and pancreatic secretion of bicarbonate when the pancreatic juice was allowed to flow into the duodenum, whereas no increase in either the secretin concentration or bicarbonate output was apparent using the same amount of Lipomul when the pancreatic juice was diverted from the duodenum. In 4 of these 7 dogs so studied, intraduodenal administration of oleic acid emulsion, with pH adjusted to 5.0 in graded doses, resulted in a dose-related increase in the secretin concentration that paralleled pancreatic bicarbonate output. The increases in both secretin concentration and pancreatic bicarbonate secretion were completely abolished by intravenous infusion of a rabbit antisecretin serum in the 4 dogs. Thus we conclude that release of endogenous secretin plays an important role in the mechanism of exocrine pancreatic secretion stimulated by digestive products of fat in dogs.
Plasma surface modification technique was used to add amino groups onto the surfaces of polypropylene beads by exposing them to anhydrous ammonia plasma. Through these amino groups, albumin was attached to the polypropylene beads. Attached albumin was further stabilized by crosslinking with glutaraldehyde. The effect of washing albuminated polypropylene beads with saline and human plasma was investigated. It was found that after initial rapid removal of albumin, the concentration of attached albumin tended to reach a steady-state. After 52 h of washing, the amount of albumin retained on the beads varied between 125 and 171 micrograms/cm2.
We investigated a possible role of endogenous cholecystokinin-pancreozymin (CCK-PZ) in the mechanism of exocrine pancreatic secretion after excluding pancreatic juice from the intestine in rats. Fasting plasma immunoreactive CCK-PZ was determined in normal rats, in rats with pancreatic duct ligation, and in sham-operated rats. The mean fasting plasma CCK-PZ concentration of rats with pancreatic duct ligation, 25.1 +/- 2.0 pM, was significantly greater (p less than 0.001) than those of normal and sham-operated rats, 14.3 +/- 1.7 and 11.5 +/- 2.2 pM, respectively. Whereas mean postprandial plasma CCK-PZ concentrations of normal and sham-operated rats were significantly greater (p less than 0.001) than their fasting levels, no significant increase occurred in the rats with pancreatic duct ligation after a meal. The mean fasting plasma CCK-PZ concentration of rats with pancreatic duct ligation was comparable to the mean postprandial CCK-PZ level of normal and sham-operated rats. To determine a possible role of circulating endogenous CCK-PZ on the pancreatic secretion, anesthetized rats were prepared with ligation of pylorus and cannulation of pancreatic duct. After diversion of pancreatic juice began, pancreatic secretion including protein significantly increased, which coincided with a significant increase in plasma CCK-PZ concentration. The increases in both pancreatic secretion and plasma CCK-PZ were reversed by intraduodenal administration of bovine trypsin or rat pancreatic juice. Furthermore, the increase in pancreatic secretion was abolished by intravenous infusion of proglumide or an intravenous bolus injection of a rabbit anti-CCK-PZ serum, which also blocked clearly the increase in the pancreatic secretion stimulated by exogenous CCK-PZ8 (0.125 micrograms X kg-1 X h-1) in rats. Thus we conclude that the increase in pancreatic secretion resulting from elimination of pancreatic juice from the intestine is attributable, in part, to increased release of CCK-PZ, and thus it is suggested that trypsin in the intestinal lumen plays a significant role in release of CCK-PZ.
Coated charcoal hemoperfusion started in the earlier grades of coma appears to improve the survival rate of drug-induced FHF. This is based on randomized control animal studies and clinical trials using historical controls. Even if randomized clinical trials in patients should substantiate these findings, it is still a very small step in artificial liver support. Viral-induced FHF and cirrhotic encephalopathy are much more common conditions that still cannot be supported. However, this initial promising step should encourage us to become more optimistic about the possibility of developing artificial livers for the higher levels of support. A multifaceted approach in research should include evaluations of combined approaches. Increased basic knowledge in toxic and essential substances will be another important requirement.
To determine the effect of a fraction of licorice extract, FM100, on the endogenous release of secretin and exocrine pancreatic secretion, five dogs were prepared with chronic pancreatic fistulas and gastric cannulas. Intraduodenal administration of licorice extract (pH 7.4) in three different doses (0.5, 1.0, and 2.0 g) resulted in significant increases of both plasma secretin concentrations and pancreatic bicarbonate secretion in a dose-related manner. The plasma secretin concentration and pancreatic bicarbonate output produced by licorice extract correlated well. Intragastric administration of licorice extract (2 g) in 5% liver extract meal (in which pH was maintained at 5.5 by the intragastric titration method) resulted in significant increases of both plasma secretin concentration and pancreatic bicarbonate output. The increase in pancreatic bicarbonate secretion was completely abolished by intravenous infusion of a rabbit antisecretin serum in the two dogs so studied. Thus, the present study indicates that the endogenous release of secretion is involved in a mechanism of an increase in exocrine pancreatic secretin induced by FM100.
We investigated the effect of fat in the duodenum on the gallbladder emptying in seven dogs prepared with gastric, duodenal, and gallbladder cannulas. Gallbladder volume was measured at 15-min intervals, and venous blood samples were obtained at regular intervals for 2.5 h. Intraduodenal administration of Lipomul (pH 5.0, corn oil) in three different doses (1.1, 2.2, and 4.4 mmol/10 min) resulted in significant increases in gallbladder emptying in a dose-dependent manner (r = 0.8668, P less than 0.001). Likewise, the increase in integrated cholecystokinin (CCK) release in response to Lipomul was also dose dependent (r = 0.7334, P less than 0.001). A statistically significant correlation was found between integrated CCK release and gallbladder emptying in response to Lipomul (P less than 0.001). To determine the role of circulating endogenous CCK on gallbladder emptying effects of intravenous administration of proglumide and a rabbit anti-CCK serum on gallbladder emptying were studied. Gallbladder emptying was virtually abolished by the antiserum. Proglumide not only abolished the emptying but also increased gallbladder volume. Thus we conclude that in dogs the gallbladder emptying in response to fat in the upper small intestine depends on increased circulating endogenous CCK.
We investigated a hormonal mechanism involved with cyclic pancreatic secretion in interdigestive state in four dogs prepared with gastric and modified Herrera's pancreatic cannulas and four dogs prepared with gastric and Thomas' duodenal cannulas. Cholecystokinin-pancreozymin (CCK-PZ), secretin, pancreatic polypeptide (PP), and motilin were considered as candidate hormones that might be involved in the mechanism. Radioimmunoassays of the four hormones in serial plasma samples showed cyclic increases in only two hormones including motilin and PP, which coincided with the cyclic increase in pancreatic secretion. However, only motilin given intravenously produced a cyclic pancreatic secretion similar to spontaneous cyclic pancreatic secretion in interdigestive state. Although the magnitude of peak pancreatic secretion was not altered during intravenous infusion of motilin in doses of 0.06 microgram X kg-1 X h-1 or 0.06 microgram/kg, the peak secretion occurred more frequently than that during the control interdigestive state. Atropine administered intravenously abolished the cyclic increases in both plasma motilin concentration and pancreatic secretion. Exogenous secretin, CCK-PZ8 and PP failed to produce cyclic pancreatic secretion. To further elucidate the mechanism involved, the effect of intravenous infusion of a rabbit anti-CCK-PZ or antimotilin serum on the cyclic pancreatic secretion was studied. The antimotilin serum completely blocked the pancreatic secretory cycles in two dogs so studied, whereas rabbit anti-CCK-PZ serum did not influence the pancreatic cycle in two dogs. We conclude that circulating motilin plays an important role on the development of cyclic increase in the pancreatic secretion in two dogs so studied.(ABSTRACT TRUNCATED AT 250 WORDS)
Five hemodialysis patients were treated with combined hemodialysis-hemoperfusion with their conventional hemodialyzer plus a 70-gram ultrathin collodion coated activated charcoal device for a total of 63 months. Indications for this therapy included pericarditis, peripheral neuropathy, clotting of conventional hemodialyzers and reduction of dialysis time and frequency. The outcome was beneficial in all cases and stable biochemical and hematological parameters were maintained. No increase in heparin requirements was noted and the therapy was thought to be cost-effective.
Rat liver microsomes and cytosol have been co-immobilized by microencapsulation into artificial cells. The immobilized enzyme retained good enzyme activity. Enzyme kinetics, storage stability, pH profiles and temperature profiles have been analyzed.
Cross-linking hemoglobin (Hb) into Polyhemoglobin (PolyHb) for use as an artificial blood substitute may affect its antigenicity. To investigate this, male Sprague-Dawley rats are immunized with one of the following: rat stroma-free Hb (rSFHb), rat PolyHb (rPolyHb), human stroma-free Hb (hSFHb), and human PolyHb (hPolyHb). Antibody titers are quantified using a double antibody radioimmunoassay. These results show that more antibodies are produced to hPolyHb than to hSFHb, whereas rSFHB and rPolyHb are relatively non-antigenic. Thus, under homologous conditions, cross-linking hemoglobin does not significantly increase its antigenicity, whereas under heterologous conditions the molecule becomes more antigenic.
The author reviewed artificial cells and their applications in hemoperfusion for chronic renal failure, poisoning, fulminant hepatic failure, removal of aluminium and iron, and metabolic assists. Other areas reviewed included artificial cells containing enzymes, multienzymes, immunosorbents, cell cultures and other areas. Artificial cells can be formed as membrane coated adsorbent or microencapsulated adsorbent, enzymes and cells. The large surface to volume relationship and the ultrathin membrane of artificial cells allows the rapid equilibration of metabolites. Artificial cells containing enzymes, ion exchange resin and activated charcoal have been used for hemoperfusion. The microencapsulated or membrane coated absorbents, enzymes, cells, immunosorbents and other material are prevented from releasing unwanted material into the circulation and prevented from adverse effects on blood cells. Because of the problem of charcoal in releasing emboli and depleting platelets we first developed coated activated charcoal hemoperfusion for clinical application. This has been used extensively in clinical studies. The artificial cell approach has also been applied to a number of other hemoperfusion approaches. The lack of space only allows this paper to summarize some of the approaches originated from this research centre.
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Suspension of living hepatocytes were microencapsulated inside 300 micron mean diameter alginate artificial cells. The galactosamine fulminant hepatic failure rat model was used. 48 hours after the injection of galactosamine, grade II coma hepatic failure rats were divided into pairs. One of the pair was randomly chosen for the control group, and the other for the treated group. Each rat in the control group received one peritoneal injection of microcapsules containing no hepatocytes. Each rat in the treated group received one peritoneal injection of microcapsules containing hepatocytes. The survival of the treated group is significantly higher than the control group.
A rapid reversed-phase high-performance liquid chromatography method was developed for the isolation of small quantities of biologically active gastrointestinal hormones, using a Varian MCH-10 C18 column. Biologically active secretin was isolated from contamination with other hormones, including cholecystokinin, gastrin, motilin, and vasoactive intestinal polypeptide, from samples of the acid perfusate of canine duodenum and from the crude acetic acid extract of canine antral mucosa containing less than 100 picomoles of secretin. The method also appeared to be suitable for the isolation of cholecystokinin octapeptide and motilin.
Phenylalanine ammonia-lyase immobilized within semipermeable microcapsules has an assayed enzyme activity which is 20% +/- 4% of the enzyme in free solution. The Km for the immobilized enzyme remained the same as that of the free enzyme. The pH optimum also remained unchanged at pH 8.5 +/- 1.0. At the lower pH range, enzyme activity is higher for the immobilized enzyme. Daily oral administration of microencapsulated phenylalanine ammonia-lyase to phenylketonuric rats decreased the systemic phenylalanine level by 35 +/- 8% in 2 days (P less than 0.05) and by 75 +/- 8% in 7 days (P less than 0.001).
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We studied the effect of hydrochloric acid (HCl) in the proximal small intestine on release of cholecystokinin (CCK) and secretin and on exocrine pancreatic secretion in conscious dogs with gastric cannulas and modified Herrera pancreatic cannulas. Intraduodenal administration of HCl in a concentration of 50 or 100 mM at rates of 0.05, 0.1, 0.2, and 0.4 mmol/min significantly increased plasma concentration of CCK in a dose-dependent manner, whereas plasma gastrin levels decreased. The increased plasma CCK level paralleled a significant increase in pancreatic trypsin output. Plasma secretin concentration and pancreatic bicarbonate output also increased in response to the acid, and the increase was dependent on the acid loads delivered in the duodenum. Thus, in dogs, HCl in the duodenum releases both CCK and secretin to stimulate pancreatic secretion of bicarbonate as well as enzymes.