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Biomedical subjects

T M Chang

Publications and source records attributed to T M Chang.

At least 289 records · Page 16Linked to original sources

Plasma secretin concentrations and gastric pH in healthy subjects and patients with digestive diseases.

Plasma secretin concentrations were determined in healthy subjects and patients with duodenal ulcer, achlorhydria, and celiac sprue. Mean fasting plasma secretin concentrations in 26 healthy subjects and 26 duodenal ulcer patients were 6.7 +/- 0.5 and 10.2 +/- 1.2 pg/ml, respectively, and were significantly different (P less than 0.02). After ingestion of a standard meat meal, pyloric pH decreased to less than 4.5 within 15 min and plasma secretin concentrations significantly increased in all 52 subjects. In 14 subjects (seven healthy subjects and seven patients with duodenal ulcer), no significant rise in plasma secretin concentration occurred when pyloric pH was maintained at greater than 5.0 by intravenous cimetidine (600 mg) and intragastric antacid. In 10 achlorhydric patients, intragastric pH remained greater than 5.0 after the meal and plasma secretin concentrations did not change. However, plasma secretin concentrations increased significantly when 0.1 N HCl was infused in the stomach (25 mEq/hr) during the postprandial period. In all eight adult patients with celiac disease (seven untreated, one partially treated), pyloric pH remained less than 4.0 after a meal. Postprandial secretin concentrations did not increase significantly in six and showed a transient rise in two. These studies show that (1) plasma secretin concentration increases significantly after meals in healthy subjects and patients with duodenal ulcer; (2) neutralization of gastric acid and the achlorhydric state show no significant postprandial rise in plasma secretin concentration; (3) achlorhydric patients do not have a defect in secretin release in response to acid; and (4) failure of postprandial rise in plasma secretin in patients with celiac disease is attributed to impaired release of secretin and in achlorhydric patients it is attributed to lack of acid secretion.

Achlorhydria↗

Motilin-antimotilin reaction reveals two antigenic determinants in motilin.

The reaction of motilin with four rabbit antimotilin sera raised by immunization with synthetic porcine motilin-bovine serum albumin conjugate was studied with respect to various binding parameters and specificity. All four antisera exhibited an extremely high degree of specificity and high affinity (K greater than 10(11) M-1) for porcine motilin. Studying the various synthetic motilin fragments. These antisera appeared to contain binding sites reacting strongly with the N-terminal sequence in which the first three amino acid residues are essential for high affinity binding. One of the antisera, R-3-6, appeared to contain approximately 20% of its binding sites with high affinity for C-terminus-containing fragments. These results suggest that motilin possesses two antigenic domains along its primary structure; one contains the N-terminal tripeptide and the other contains the C-terminal nanopeptide as essential parts. Thus, in addition to heterogeneity in affinity, a given antibody preparation may be heterogenous with respect to the specificity along the sequence of a peptide. Gel filtration studies of the methanol extracts of human and dog plasma indicated that an immunoreactive motilin-like material with a molecular size similar to natural porcine motilin was measured by our routine radioimmunoassay.

Animals↗

Identification, characterization and distribution of motilin immunoreactivity in the rat central nervous system.

Motilin-immunoreactivity was evaluated in rat brain using 15 different antisera and by combining gel filtration, high pressure gel filtration and reverse phase high pressure liquid chromatography with radioimmunoassay. Gel filtration chromatography demonstrated a high molecular weight and low molecular weight form of immunoreactive motilin. The high molecular weight form predominated in brain while the low molecular weight peptide was the predominant form of duodenum. The low molecular weight immunoreactive motilin was indistinguishable from synthetic porcine motilin by gel filtration and high molecular weight gel filtration. Low molecular weight rat motilin could, however, be distinguished from synthetic porcine motilin by high pressure liquid chromatography and certain antisera. Immunological results suggest that the slight structural difference may be in the N-terminal portion of the molecule. Immunoreactivity was measured in grossly and microdissected regions of the rat brain. The peptide had quite a unique distribution as highest concentrations are observed in the cerebellum. High concentrations were also observed in hypothalamic nuclei. Particularly high concentrations were noted in the organum vasculosum lamina terminalis. Lowest motilin concentrations in the rat brain were in the pons and the medulla. The distribution of motilin in rat brain suggests that it may have roles in regulating both neuroendocrine and neurological processes.

Animals↗

Mapping of motilin-immunoreactive neurons of the rat brain.

Motilin immunofluorescence was observed in the rat brain by means of N- and C-terminally directed antisera. A detailed mapping of the localization of motilin-like immunoreactive neurons in the rat forebrain is presented. Colchicine pretreatment revealed many cell bodies in the mediobasal hypothalamus. A small number of cells were observed in the organum vasculosum lamina terminalis (OVLT) region. A rich innervation of varicose fibers was observed in the median eminence and OVLT. Fibers of varying densities were observed in the preoptic area, nucleus interstitialis stria terminalis, hypothalamic nuclei, basal hypothalamus, amygdala, mammillary doby and central gray. The localization of these neurons suggests that motilin, like other brain peptides serves a variety of functions including neuroendocrine regulation.

Amygdala↗

The release of biologically active secretin-like immunoreactivity into duodenal lumen of dogs.

1. Immunoreactive secretin in the duodenal contents was determined in four conscious and four anaesthetized dogs in which hydrochloric acid (0.1 N) was infused into the duodenum at 2.2 ml./min. In the conscious dogs, immunoreactive secretin concentration in duodenal juice increased from 5-7 to 40-60 ng/ml. after infusion of HCl. In anaesthetized dogs, luminal immunoreactive secretin concentration increased from 2-3 to 12-16 ng/ml. after acid infusion. In both groups of dogs, a 20- to 30-fold increase in the total output of luminal immunoreactive secretin was observed. 2. Duodenal juice collected from anaesthetized dogs after diversion of both bile and exocrine pancreatic secretion was found to be the only source of luminal immunoreactive secretin. No immunoreactive secretin was found in either bile or pancreatic juice. 3. Gel filtration of the duodenal juice on a Sephadex G-50 column indicated that the immunoreactive secretin-like material in the duodenal juice possesses a molecular size similar to that of natural porcine secretin. 4. Immunoreactive secretin was partially purified from dog duodenal juice by chromatography on a SP-Sephadex column and found to be capable of stimulating pancreatic bicarbonate and water secretion in dogs.

Animals↗

Secretin is an enterogastrone in the dog.

To determine the physiological significance of secretin on gastric secretion, effects of normal rabbit serum (control) and rabbit antisecretin serum (anti-S) on meat meal-stimulated gastric secretion of acid and pepsin from vagally innervated fundic pouches were studied in four dogs with gastric fistulas. The intravenous administration of control serum did not affect the postprandial rise in plasma secretin concentration, whereas intravenous anti-S virtually eliminated the circulating plasma secretin. Both plasma gastrin concentration and acid output following intravenous anti-S were significantly greater than those following intravenous control serum. However, pepsin outputs in the two groups of experiments were not significantly different. In the same dogs in the fasting state, during intravenous infusion of secretin in doses of 0.06 and 0.125 U . kg-1 . h-1, the acid output stimulated by intravenous human synthetic gastrin in a dose of 0.25 micrograms . kg-1 . h-1 was significantly less than that during intravenous saline. The studies indicate that secretin in a physiological dose can inhibit postprandial release of gastrin and gastric secretion of acid, and thus secretin is an enterogastrone in the dog.

Animals↗

Tyrosinase immobilized within artificial cells for detoxification in liver failure: II. In vivo studies in fulminant hepatic failure rats.

Galactosamine-induced fulminant hepatic failure rats were used for in vivo studies of the removal of tyrosine and total free phenol by means of hemoperfusion over immobilized tyrosinase within artificial cells. The elevated plasma tyrosine level was decreased to about half the value after one hour of hemoperfusion. The studies of tyrosine clearance suggest that it is efficient and remains constant throughout the one-hour hemoperfusion. In those galactosamine-induced fulminant hepatic failure rats with increased total free phenol levels hemoperfusion over tyrosinase artificial cells significantly lowered the level.

Animals↗

Effects of temperature on the removal of urea as ammonia by enzymatic conversion and by gas absorption using an oxygenator.

Urea in dialysate solution was converted by urease into ammonium and bicarbonate. Ammonium and bicarbonate can be removed using a gas absorption unit (e.g. oxygenator) to remove ammonia gas and carbon dioxide. The times for the total ammonium levels in the dialysate to be lowered by 50% were 95 minutes at 25 degree C and 15 minutes at 60 degree C. Increasing the dialysate temperature alone was effective in increasing the removal of ammonium, without the need to add NaOH.

Absorption↗

Effect of sodium oleate on plasma secretin concentration and pancreatic secretion in dog.

The effects of sodium oleate and triglyceride infused into the duodenum of dogs with chronic pancreatic fistulas on pancreatic secretion and plasma immunoreactive secretin were investigated. The responses were compared with those following intravenous secretin infusions. Oleate markedly increased pancreatic water and bicarbonate secretion in a dose-related fashion, and these increases were accompanied by a small, but significant rise in the level of circulating immunoreactive secretin. No change in pancreatic secretion or in plasma secretin level was observed by the administration of triglyceride. Comparison of the bicarbonate response after oleate infusion with that after secretin administration suggests that the pancreatic stimulatory effect of intraduodenal sodium oleate is mediated to a major extent by the release of endogenous secretin.

Animals↗

Soluble liver extract as supplement to detoxification by hemoperfusion in liver failure.

Charcoal hemoperfusion has been effective in reversing grade IV hepatic encephalopathy in patients. In animal studies essential factors have to be added to result in significant increase in the survival rate of grade III coma rats treated by hemoperfusion. In the present study, a water soluble liver extract was prepared and injected intraperitoneally into fulminant hepatic failure rats in grade II hepatic coma. This significantly (p less than 0.001) increased the survival time in these animals. However, no significant increase in survival rate was obtained. We were also able to significantly (p less than 0.0005) control gastrointestinal bleeding in the treated rats. We postulate that this supplementation of essential factors in combination with detoxification using hemoperfusion could form the basis of a more complete artificial liver support system.

Animals↗

Radioimmunoassay of secretin. A critical review and current status.

The radioimmunoassay methods of secretin are reviewed with respect to production of antibody, preparation of radioactive tracers, and effect of plasma interference. The major difference in the secretin assay methods resides in handling plasma interference. Thus the assay sensitivity decreased markedly when the assay was conducted by diluting plasma samples. When the assay was conducted by compensating for plasma interference with homologous hormone-free plasma, the effect of plasma interference was greatly reduced, leading to a more sensitive assay. However, this method probably can not obtain consistent results with plasma samples collected under various experimental conditions. The method is still subject to considerable desensitization and assay variation. On the other hand, the elimination of plasma interference before assay results in the most sensitive secretin assays capable of detecting consistently a significant postprandial rise in plasma secretin level. It is concluded that a sensitive, validated secretin radioimmunoassay should be one that is capable of detecting increments of plasma secretin in response to doses of intraduodenal acid at 0.055 mEq/min or lower and intravenous administration of exogenous secretin at 0.03 CU/kg/hr with concomitant stimulation of pancreatic bicarbonate and water secretion. With a sensitive and accurate radioimmunoassay for secretin, it is now possible to further investigate the physiology and pathophysiology of secretin.

Acids↗

24-Hour plasma secretin level and pancreatic secretion in dog.

Plasma secretin concentrations were determined and duodenal pH was recorded continuously for a period of 24 hours after ingestion of a meal in 3 dogs with gastric cannula and duodenal cannula and in 4 dogs with pancratic fistulae. The mean plasma secretin concentration increased significantly after a meal and it remained elevated for the first 12-hour period (peak at 30 min). Duodenal pH frequently decreased below 4.5 during the first 12-hour postprandial period, but it remained above 5.0 during the second 12 hours. Pancreatic secretion peaked during the first hour of meal ingestion and remained elevated until the end of 12 hours. The increased plasma secretin level in pancreatic fistula dog during the postprandial period was significantly greater than that of duodenal cannula dog, but the trends of increase in the secretin levels were quite identical. The present study indicates that: (1) plasma secretin concentration increases significantly within 30 min after a meal and remains increased during the first 12-hour period, (2) duodenal pH frequently decreaded below 4.5 during the same 12 hours but more frequently during the first 6 hours, and (3) a significant increase in pancreatic water, HC03- and protein occurred during the same time period.

Animals↗

The effects of homologous cross-circulation and in situ liver perfusion on fulminant hepatic failure rats.

A galactosamine-induced fulminant hepatic failure (FHF) rat model was used to study the effects of homologous cross-circulation and in situ liver perfusion. Cross-circulation with homologous donors did not significantly improve the survival time or recovery rate of grade II hepatic coma rats. Homologous in situ liver perfusion significantly improved the survival time and recovery in FHF only when started in grade II coma; it has no effect in the later stage of coma.

Animals↗

ACAC (albumin-collodion coated activated charcoal) hemoperfusion: in-vitro removal and clearance of theophylline.

This study was designed to evaluate the effectiveness of ACAC charcoal to remove theophylline. Activated charcoal prepared according to Chang's technique was used in in vitro batch and clearance experiments. Theophylline was removed with a T1/2 of less than 5 minutes in the stirred batch experiments. The clearance studies showed values of 102, 145, and 208 ml/min (extrapolated to 300 g of ACAC charcoal), for extrapolated flow rates of 120, 240, and 360 ml/min. The ACAC charcoal is very efficient in removing theophylline in vitro from an aqueous solution. The efficiency of ACAC hemoperfusion for the treatment of severe, acute theophylline intoxication has also been demonstrated here.

Albumins↗

Effects of air and fluid flow rates on removing different concentrations of urea and ammonia from fluid by gas absorption in a capillary hemodialyzer.

Urease converts urea into ammonium and bicarbonate. Alkalinization converts ammonium into free ammonia which can be removed as a gas. Our approach is to use a capillary hemodialysis as a gas absorption unit with liquid moving through the blood compartment and air through the dialysate compartment to extract ammonia gas. This paper examines the effects of air flow rate, fluid flow rate, and concentrations of ammonia (and urea) in the fluid. It was observed that increasing air flow rate or dialysate flow rate increases the mass transfer rate for ammonia especially at low ammonia concentration levels. Ammonia removal rate increases with air flow rate linearly. Ammonia removal rate increases with increasing fluid flow rate, but reaches a plateau when flow rate was above 500 ml/mn.

Air↗

The effects of polymer-solvent compositions on the formation of collodion membrane artificial cells.

This study is an attempt to analyze the various polymer-solvent compositions for preparing collodion membrane artificial cells for biomedical applications. Cellulose nitrate was disolved in different mixtures of alcohol-ether solutions and used for microencapsulation. The most optimal solvent solution consisted of 4 g% cellulose nitrate in 17.5% (volume) alcohol and 82.5% (volume) ether. The urease microcapsules prepared this way showed no leakage of enzyme under test conditions. Having established the optimal polymer-solvent compositions, an easier and more reproducible procedure has been established for preparing collodion membrane artificial cells.

Capsules↗