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Biomedical subjects

T M Chang

Publications and source records attributed to T M Chang.

At least 109 records · Page 6Linked to original sources
PubMed1994

Effect of digested protein on pancreatic exocrine secretion and gut hormone release in the dog.

The hormonal mechanisms mediating protein-stimulated pancreatic exocrine secretion were investigated in four conscious dogs with gastric cannulas and Thomas duodenal cannulas. Pancreatic juice was collected by direct cannulation of the main pancreatic duct in response to intraduodenal infusates prepared with cooked beef liver. When the homogenized liver was administered intraduodenally, cholecystokinin (CCK) in plasma significantly increased. This increase was accompanied by a significant increase in pancreatic exocrine secretion, including volume, bicarbonate, and protein output. The liver homogenate incubated with pancreatic enzymes further increased both plasma CCK and exocrine pancreatic secretion. However, plasma secretin was not affected by the protein digests. Intravenous administration of loxiglumide at the rate of 5.0 and 10.0 mg/kg/h resulted in a significant decrease in the stimulated pancreatic secretion of fluid, bicarbonate, and protein. The study indicates that endogenous CCK released by protein digests exerts not only enzyme secretion but also bicarbonate secretion in dogs.

Animals↗
PubMed1994

Xenotransplantation of microencapsulated canine islets into diabetic rats.

Islets of Langerhans were isolated in high yields from canine pancreata. In the procedure, the pancreata were perfused and digested with collagenase, and the islets were then purified on histopaque density gradients. As many as 60,000 islets were isolated from a single pancreas. Islets were encapsulated in alginate-polylysine-alginate membranes with the aid of an air-jet droplet generator. In vitro studies demonstrated that the isolated and encapsulated islets secreted insulin in response to glucose and IBMX challenge for at least 9 weeks. In in vivo studies 6 diabetic Wistar rats were transplanted with 5,000 to 8,000 encapsulated islets each. The diabetic condition was reversed in all recipients for up to 112 days. In control animals, which received free, unencapsulated islets, the xenografts remained functional for fewer than 21 days. Microcapsules retrieved from normoglycemic transplant recipients 1 and 2 months posttransplantation were shown to contain viable islet tissue, and no cellular overgrowth was observed on capsular surfaces. The results of the study indicate a considerable clinical potential of microencapsulated canine islet xenografts.

Alginates↗
PubMed1994

Mechanism of action of insulin on pancreatic exocrine secretion in perfused rat pancreas.

In conscious rats, we have previously shown that immunoneutralization of circulating insulin with a rabbit anti-insulin serum abolished the pancreatic exocrine secretion stimulated by a meal or a combination of exogenous secretin and cholecystokinin octapeptide (CCK-8). To investigate the mechanism of endogenous insulin action on the exocrine pancreas, isolated rat pancreata were perfused with intra-arterial infusion of Krebs-Henseleit solution (37 degrees C) at 1.2 ml/min, whereas both pancreatic juice and portal venous effluent were collected separately in 15-min samples. Simultaneous intra-arterial infusion of secretin and CCK-8 in doses of 0.75 and 4.2 pmol/h; respectively, significantly increased volume, bicarbonate, and protein output in 7 rat pancreata (P < 0.01). When a rabbit anti-insulin serum was administered intra-arterially (0.1-ml bolus followed by 0.1 ml for 10 min), pancreatic secretion of volume, bicarbonate, and protein output was profoundly suppressed (n = 7, P < 0.01), whereas a normal rabbit serum failed to influence pancreatic secretion. The decrease in pancreatic secretion by the antiserum coincided with a significant increase in somatostatin in portal venous effluent from 1.4 +/- 0.2 to 4.1 +/- 0.8 pM (n = 6, P < 0.05). The combined administration of a rabbit antisomatostatin serum (0.4 ml) and the anti-insulin serum partially reversed the effect of the anti-insulin serum alone. Thus the pancreatic secretion was significantly greater than that achieved by the anti-insulin serum alone (P < 0.05). These observations strongly suggest that the action of insulin on exocrine pancreas is mediated by its local or paracrine action.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effect of protein derivatives on pancreatic secretion and release of secretin and CCK in rats.

We investigated the effect of intraduodenal administration of oligopeptide and a mixed amino acid solution, which contains the same amino acid composition as oligopeptide, on pancreatic exocrine secretion and the release of secretin and cholecystokinin (CCK). Anesthetized rats were prepared with pyloric ligation and cannulation of pancreatic duct and bile duct. Protein derivatives in three different doses (oligopeptide: 25, 100, and 400 mg/h; and mixed amino acid solution: 70, 140, and 280 mg/h, pH 7.0) were infused into the duodenum for 1 h. Pancreatic juice was collected, and plasma concentrations of secretin and CCK were measured by radioimmunoassay. In addition, the effect of intravenous injection of an antisecretin serum or a CCK antagonist, loxiglumide, on pancreatic secretion stimulated by oligopeptide or mixed amino acid solution was also studied. Oligopeptide produced a significant dose-related increase in pancreatic secretion including volume, HCO3-, amylase, and trypsin output, plasma secretin (r = 0.792, P < 0.001), and plasma CCK (r = 0.421, P < 0.01). Similarly, mixed amino acid solution produced a dose-related increase in pancreatic juice volume, HCO3-, amylase, and trypsin output. Compared with CCK, the percentage increase in plasma secretin was 7.3x and 2.8x higher in response to oligopeptide (400 mg/h) and mixed amino acid solution (280 mg/h), respectively. An antisecretin serum almost completely inhibited volume flow and HCO3- output stimulated by oligopeptide as well as mixed amino acid solution, but not amylase and trypsin output. In contrast, loxiglumide significantly suppressed amylase and trypsin output stimulated by protein derivatives, but did not affect volume flow or HCO3- output.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1994

Secretin: a physiological regulator of gastric emptying and acid output in dogs.

Secretin has been known to inhibit gastric acid secretion in several species. However, the physiological role of secretin on the postprandial acid output and gastric emptying in an intact stomach remains controversial. In the present study, we reinvestigated the role of secretin in physiological dose range and endogenous secretin on gastric acid secretion and emptying in the stomach without influencing intragastric luminal pH in dogs. In seven conscious dogs with gastric cannulas, a 4% amino acid meal was administered intragastrically, and three different doses of secretin and an antisecretin serum were infused intravenously in each dog on separate days. Gastric emptying and net acid output were measured using a dye dilution technique, and plasma secretin and gastrin were determined by specific radioimmunoassays. After the meal, gastric emptying was exponential: acid output peaked at 25 min, and plasma concentrations of gastrin and secretin peaked at 15 and 60 min, respectively. Intravenous infusion of secretin at 1.25, 2.5, and 5.0 pmol.kg-1.h-1 dose dependently increased plasma levels of the peptide and suppressed postprandial plasma gastrin response and gastric acid output and emptying of the meal. Immunoneutralization of circulating secretin with a rabbit antisecretin serum abolished the postprandial rise of plasma secretin and significantly increased plasma gastrin, and augmented gastric emptying as well as acid output. It is concluded that, in dogs, secretin plays a physiological role in the regulation of gastric emptying and acid output after a liquid amino acid meal and that these effects may be mediated in part by suppression of the release of gastrin.

Animals↗
PubMed1994

Assessment of blood substitutes: I. Efficacy studies in anesthetized and conscious rats with loss of 1/3, 1/2 and 2/3 blood volume.

Acute and long-term recovery (14 days) studies were conducted in conscious rats bled 1/3, 1/2, and 2/3 blood volume, and in anesthetized rats bled 1/3 volume. Study I: bled 1/3 blood volume. Study Ia: Anesthetized rats bled 1/3 blood volume were in shock and most died within 1 hour; the group which received infusion of 3x volume Ringer's lactate regained blood pressure with 100% long-term recovery. Study Ib: In conscious rats bled 1/3 blood volume, blood pressure did not fall to shock levels, and the long-term recovery in both the control group and the group which received 3x volume Ringer's lactate was 100%. Study II: Bled 1/2 blood volume. In conscious rats bled 1/2 volume, the blood pressure of the control group was slightly above 70 mmHg. Infusion of 3x volume Ringer's lactate or 7 gm% human albumin in Ringer's lactate increased blood pressure to above 90 mmHg in the acute study. Long-term recovery and survival rate was 80% in both the controls and the Ringer's lactate group, and 100% in the albumin group. Study III: bled 2/3 blood volume. In conscious animals, loss of 2/3 blood volume resulted in fall of blood pressure to shock levels and death of the animal within 1 hour. Infusion of 3x volume Ringer's lactate did not increase blood pressure to above shock level. Stroma-free hemoglobin and polyhemoglobin increased blood pressure, and whole blood returned blood pressure to normal. In long-term recovery, poly-hemoglobin, but not SFHb, was as effective as whole blood with 100% long term recovery. Animal models in Study I and II are suitable only for studies of volume replacement. Animal models in Study III, especially using long-term recovery studies, are more suitable for studying both volume and red blood cells replacements.

Anesthesia, General↗
PubMed1994

Assessment of blood substitutes: II. In-vitro complement activation of human plasma and blood for safety studies in research, development, industrial production and preclinical analysis.

Animal safety study cannot predict the effects of blood substitutes in human response. Response of human, especially in immunology and complement activation, need not be the same as those in animals. We have earlier reported an in-vitro preclinical screening test based on testing the effects of modified hemoglobin on complement activation of human plasma or blood in vitro. In this test, modified hemoglobin is added to human plasma in a test tube. Complement activation is followed by the C3a levels. Since this directly measures the effect of modified hemoglobin on human plasma, it would be the closest response in human next to injecting this into human. Thus, this could be an important bridge before clinical use in patients. However, why wait for the completion of research, industrial production and preclinical animal studies? Why don't we do this test right at the beginning during the research stage? If a new system is found to cause complement activation at this stage, one can avoid tremendous waste of time and money in further development, industrial production and preclinical animal study. This paper analyzes this approach in research, development, industrial production and preclinical analysis.

Blood Substitutes↗
PubMed1994

Human hemoglobin anaerobically reacted with divinyl sulfone: a source for oxygen carriers.

Human hemoglobin (HbA) was reacted in anaerobic conditions with divinyl sulfone (DVS). The structural and oxygenation properties of the resulting chemically-modified product were studied in order to assess its potential as a physiological oxygen carrier. The reaction was carried out anaerobically at 25 degrees C and pH 7.4 for 3 h. Quenching was performed with lysine-HCl solution and the resulting solution dialysed to remove unbound DVS and excess lysine. The product, designated Poly HbA-DVS, was characterized structurally using gel-permeation HPLC and SDS-PAGE and functionally employing a Hemox-analyzer at 37 degrees C and pH 7.4. From gel-permeation HPLC it was estimated that about 60% of the starting material was polymerized, with a molecular mass range from 130 to about 500 kDa, and about 40% remained monomeric with a molecular mass of 64 kDa. The virtual absence of a 32 kDa band from the SDS-PAGE pattern of the last eluting HPLC peak and the oxygenation properties of this peak material (P50 = 33 mm Hg, n = 2.2; P50 very different from the approximately 1.5 mm Hg associated with native HbA solution) indicated that the monomeric (64 kDa) component was modified, but virtually noncrosslinked, within the tetramer. The product solution, Poly HbA-DVS, had a P50 of 35 mm Hg, a Hill coefficient n of 1.8 and a methemoglobin content of 5-7%. This material has characteristics appropriate for an oxygen carrier, and can probably be used as such in perfusional and transfusional fluids.

Adult↗
PubMed1994

Toxicity of liposomes containing low mol% of dienoyl phosphocholine to blood: use of carboxymethyl chitin to reduce toxicity.

Toxic effects of liposomes composed of the synthetic lipid, 1,2-bis(octadeca-2,4-dienoyl)-sn-glycero-3-phosphocholine (C18DENPC) and cholesterol (Cho) were studied. In the present work, we have explored, 1) fusion between C18DENPC/Cho-liposomes and erythrocyte ghost (EG) membranes with resonance energy transfer assay, 2) hemolysis induced by C18DENPC/Cho-liposomes and 3) turbidity changes in native plasma on contact with C18DENPC/Cho-liposomes, in the presence or absence of carboxymethyl chitin (CM-chitin). In the absence of CM-chitin, extents of fusion, hemolysis and turbidity changes in native plasma increased with the decrease in C18DENPC content. In the presence of CM-chitin at a concentration of 10(-3) or 10(-2)% (w/v), fusion of C18DENPC/Cho-liposome with EG was inhibited. Extents of hemolysis and turbidity changes in native plasma induced by C18DENPC/Cho-liposomes were reduced depending upon CM chitin concentration.

Blood↗
PubMed1994

Submicron biodegradable polymer membrane hemoglobin nanocapsules as potential blood substitutes: a preliminary report.

We used biodegradable polymers like polylactic acid, poly-isobutylcyanoacrylate and others to prepare nanocapsules containing hemoglobin. We prepared the optimal mean diameters of between 0.08 to 0.12 micron (80-120 nm). They are spherical and homogeneous. The membrane thickness is 0.005-0.015 micron (5-15nm). With different formulation, the hemoglobin contents in the particles may be varied from 30-45%. Phospholipid is not required in bovine hemoglobin. It is required for human hemoglobin in order to retain cofactors required for optimal P50. The P50 of the biodegradable polymer membrane containing bovine hemoglobin was between 27-29 mmHg. This is the same P50 as bovine hemoglobin used in the preparation. Thus the procedure of preparation did not damage hemoglobin.

Animals↗
PubMed1993

The anaerobic reaction of bovine hemoglobin with divinyl sulfone: structural changes and functional consequences.

The anaerobic reaction of bovine hemoglobin with divinyl sulfone results in a non-cross-linked intramolecularly-modified new derivative. This chemically-modified hemoglobin is homogeneous with respect to its molecular mass (64 kDa) and electrophoretic properties. The absence of any 32 kDa band from its SDS-PAGE pattern proves the lack of intramolecular cross-linkage, while a single-peak high-performance gel-permeation chromatogram demonstrates the absence of intermolecular cross-linkage. The oxygen binding properties determined at 37 degrees C, 0.15 M Cl- and pH 7.4 display a P50 of 52 mmHg and a Hill coefficient n of 1.9. Under the same experimental conditions the oxygen affinity is not sensitive to chloride anions, suggesting that the covelant modification is in the beta-cleft. The maximum number of Bohr protons released is 0.8/tetramer, which is half that of normal bovine hemoglobin. The retention time in circulation, measured in rats, is similar to that of native bovine hemoglobin. Using a high molar ratio of divinyl sulfone to modified hemoglobin, it is feasible to effect anaerobic intermolecular cross-linkage. The polymerized material, isolated from a 24 h reaction, is a mixture of modified intermolecularly-crosslinked hemoglobins with a molecular mass range from 130 to approx. 500 kDa. The oxygen-transport characteristics of the polymerized material are similar to those of the modified non-cross-linked derivative, whereas its retention time in rats is increased three-fold with respect to native bovine hemoglobin.

Allosteric Regulation↗
PubMed1993

Characterization of secretin release in secretin cell-enriched preparation isolated from canine duodenal mucosa.

The release of secretin was studied in secretin cell-enriched preparations isolated from canine duodenal mucosa. The crude enterocytes were isolated by treating the duodenal mucosa sequentially with collagenase and ethylenediaminetetraacetic acid. Secretin cell-enriched fraction was prepared by centrifugation of the crude enterocytes in a counterflow elutriation rotor to obtain a final preparation containing 3.2 +/- 0.3 pmol/10(6) cell of immunoreactive secretin, which was 13-fold greater than the crude cell preparation (N = 5). The cells were incubated in Hanks' balanced salt solution for 20 min at 37 degrees C under 95% O2/5% CO2 before adding various agents and further incubated for various periods of time. The amounts of secretin released into the medium and retained by the cells were then determined by a specific radioimmunoassay. The release of immunoreactive secretin was increased dose-dependently over the control by dibutyryl cyclic-3',5'-adenosine monophosphate, forskolin, 4 beta-12-O-tetradecanoylphorbol-13-acetate, the synthetic serine protease inhibitor, camostat, and the calcium ionophore, A23187. The effects of forskolin, the phorbol ester, and A23187 were time-dependent and not observed at 4 degrees C. The release of immunoreactive secretin was also stimulated by KCl in high concentration and by sodium oleate. The effect of A23187 was abolished in a Ca(2+)-free medium, while those of dibutyryl cyclic-3',5'-adenosine monophosphate and forskolin were potentiated by 3-isobutyl-1-methylxanthine, which did not have a significant effect when added alone. These results indicate that the release of secretin is regulated by both Ca(2+)- and cyclic-3',5'-adenosine monophosphate-dependent mechanisms.2+ release.

Animals↗
PubMed1993

A physiological role of peptide YY on exocrine pancreatic secretion in rats.

BACKGROUND: Peptide YY (PYY) given intravenously was shown to inhibit pancreatic exocrine secretion both in the dog and the rat. However, a possible physiological role of PYY on the pancreatic secretion has not been clarified. The present study was undertaken to investigate its physiological role on the exocrine pancreas. METHODS: In conscious rats, plasma PYY was determined in response to oral ingestion of a 6-mL meal and intravenous infusion of PYY; small intestinal transit time was measured by phenol red as a nonabsorbable marker, and pancreatic secretory studies were performed in rats with pancreatic fistulas and jugular vein catheters. RESULTS: Oral ingestion of the meal (containing phenol red, 1.6 mg/100 mL) significantly increased plasma PYY within 30 minutes. During this period, most (97%) of the phenol red was detected in the proximal two-thirds of the small intestine. Intravenous infusion of PYY in 25, 50, and 100 pmol.kg-1 x h-1 produced a dose-dependent increase in plasma PYY. The dose of PYY that simulated the peak postprandial level was 50 pmol.kg-1 x h-1, and this dose of PYY significantly inhibited the pancreatic secretion stimulated by physiological doses of secretin and cholecystokinin-8 (CCK-8). After the meal, pancreatic secretion of bicarbonate and protein significantly increased in rats pretreated with normal rabbit serum, whereas this increase was significantly augmented in rats pretreated with an anti-PYY serum because the postprandial increase in plasma PYY was abolished. CONCLUSIONS: PYY plays a regulatory role in the postprandial pancreatic exocrine secretion in rats.

Animals↗
PubMed1993

Role of secretin in negative feedback regulation of postprandial pancreatic secretion in dogs.

BACKGROUND: A negative feedback regulation of pancreatic exocrine secretion has been observed in fasting rats, pigs, and humans, but this phenomenon could not be found in fasting dogs. The aims of the present study were to investigate whether or not postprandial pancreatic secretion is regulated by a negative feedback mechanism and to determine if the mechanism is mediated by secretion and/or cholecystokinin (CCK) in dogs. METHODS: In eight dogs prepared with gastric and Herrera's pancreatic cannulas, pancreatic juice was collected for 3 hours after feeding a mixed meal to measure volume, bicarbonate, and trypsin output. Peripheral venous blood was obtained to determine plasma immunoreactive secretin and CCK levels. Four groups of experiments were performed while pancreatic juice was diverted from the duodenum: (1) diversion of pancreatic juice alone, (2) intraduodenal infusion of fresh pancreatic juice while pancreatic juice was diverted, (3) intraduodenal infusion of 150 mg/h of trypsin and 300 mg/h of chymotrypsin, and (4) intraduodenal infusion of 0.1 mol/L NaHCO3. RESULTS: Pancreatic secretion during diversion of pancreatic juice was significantly greater than that obtained while pancreatic juice was returned. Diversion-induced pancreatic hypersecretion was significantly suppressed by intraduodenal administration of pancreatic proteases, but it was not influenced significantly by 0.1 mol/L NaHCO3. The suppression by either pancreatic juice or proteases paralleled the decrease in plasma secretin response, whereas the CCK response remained unchanged. The inhibitory effect of pancreatic proteases on pancreatic secretion was blocked by a physiological dose of exogenous secretin, 0.06 clinical U.kg-1.h-1. CONCLUSIONS: In dogs, postprandial pancreatic secretion is controlled by a negative feedback mechanism mediated mainly by the release of secretin, but not by CCK.

Animals↗
PubMed1993

Free and microencapsulated Erwinia herbicola for the production of tyrosine.

Erwinia herbicola (ATCC 21434) was grown in a medium which caused the cells to induce tyrosine phenol-lyase (TPL) activity. Whole cells of Erwinia herbicola were then microencapsulated within alginate-poly-L-lysine-alginate membraned microcapsules (diameter 800 microns). In a rotary shaker-incubator with a 1.9 cm horizontal throw, an agitation rate of at least 240 revolutions per minute (rpm) was required before the TPL activity of the microencapsulated cells was equal to that of the free cells. The TPL activity of the cells, whether free or microencapsulated, could be used for the conversion of ammonia, pyruvate and phenol into tyrosine at 37 degrees C. The results indicate that free cells and microencapsulated cells effect the conversion of these reactants to tyrosine equally well if the agitation rate is 240 rpm. In liver failure the concentrations of both ammonia, phenol and pyruvate are elevated. Hence the TPL activity of microencapsulated Erwinia herbicola could possibly find application in a novel approach for the removal of toxic phenol and ammonia during liver failure.

Alginates↗