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Biomedical subjects

T M Chang

Publications and source records attributed to T M Chang.

At least 217 records · Page 12Linked to original sources
PubMed1987

Recycling of NAD(P) by multienzyme systems immobilized by microencapsulation in artificial cells.

Multistep enzyme systems can be immobilized in solution within semipermeable microcapsules. With the ability to recycle cofactors, a number of potentially useful systems have been made possible. Furthermore NAD+ can be retained inside the microcapsules by two approaches. (1) NAD+ can be linked to macromolecules such as dextran or polyethyleneimine. However, in this form, there are significant increases in steric hindrance and diffusion restrictions. (2) "Artificial cells" consisting of lipid-polyamide membrane microcapsules containing multienzyme systems, cofactors, and substrates can retain NAD+ in the free form. Analogous to the intracellular environments of red blood cells, free NAD+ in solution inside the microcapsules is effectively recycled by the multistep enzyme systems which are also in solution. Enzymes in the microcapsules are in high concentrations and in close proximity to one another. Any number and any concentration of different enzyme systems can be microencapsulated all within one artificial cell, within the limit of solubility of the total amount of enzymes. Products of sequential reactions inside the microcapsules are at much higher concentrations than outside. All these factors result in an optimal intracellular environment for multistep enzyme reactions. External substrates in the form of lipophilic or small hydrophilic molecules can equilibrate across the membrane to participate as initial substrates in the multistep reactions in the microcapsules. A number of potential applications are possible using this approach. The lipid-polyamide membrane artificial cell can also be used in basic research as a biochemical cell model for the simpler types of biological cells such as erythrocytes.

Cells↗
PubMed1987

Effects of partial and total isovolemic exchange transfusion in fully conscious rats using pyridoxylated polyhemoglobin solution as a colloidal oxygen-delivering blood replacement fluid.

Stroma-free hemoglobin (SFHb) treated with pyridoxal 5'-phosphate (PP) was intermolecularly cross-linked with glutaraldehyde to give pyridoxylated polyhemoglobin (PP-PolyHb) solution (14.0 g/dl) with colloid osmotic pressure = 25 torr and a P50 = 20 torr. To evaluate PP-PolyHb as a blood substitute, fully conscious rats with chronic cannulations were subjected to blood replacement (30-100%) by a new continuous isovolemic exchange transfusion set up. Crystalline SFHb, PP-SFHb, PP-PolyHb, bovine serum albumin (BSA) and Ringer's solution were tested. Respiration, pulse and arterial blood pressure were more stable following transfusion with PP-PolyHb or PP-SFHb compared to BSA. By 7-8 days post-exchange, hematological changes returned to normal. Plasma retention of PP-PolyHb was 10-15 times longer than either crystalline SFHb or PP-SFHb for major blood exchanges. A T1/2 of 30 h was obtained for PP-PolyHb after total replacement. Long-term survival rates of 80, 63 and 50%, following replacement of 70, 85 and 100%, respectively, were significantly higher (p less than 0.05) than survival obtained for all other solutions tested. Superiority of PP-PolyHb over other fluids was clearly demonstrated.

Animals↗
PubMed1987

Effects of polylactic acid microcapsules containing prostaglandin E2 on the survival rates of grade II coma galactosamine induced fulminant hepatic failure rats.

Prostaglandin E2 was successfully incorporated into low molecular weight polylactic acid microcapsules. The size distribution of the microcapsules ranges from 20 to 50 micron. The microcapsules released drug continuously up to three days in vitro. The galactosamine induced fulminant hepatic failure rats model was used. 36 hours after the injection of galactosamine, those rats in grade II coma were chosen and pairs were matched for comparable degree of coma. Then each of the pair was randomly selected as control or treated. Each rat in the treated group received an intraperitoneal injection of PGE2 microcapsules containing 0.55 mg of PGE2. The control received blank PLA microcapsules only. The survival rate of the treated group was 40% compared to 10% in the control group. There was a significant (P less than 0.05) increase in the survival rate in the treated group.

Animals↗
PubMed1987

Effects of prostaglandin E2 on brain edema and liver histopathology in a galactosamine-induced fulminant hepatic failure rat model.

The effects of prostaglandin E2 (PGE2) on the histopathology of liver and brain edema was studied in the galactosamine-induced fulminant hepatic failure (Ga1N-FHF) rat model. The effect of PGE2 on the development of brain edema was studied in grade II coma FHF rats by electron microscopy and by measurement of brain water content and brain swelling. Electron microscopy revealed extensive pericapillary astroglial cell swelling and morphological changes of its subcellular organelles in control FHF rats. PGE2 injected FHF rats showed reduced astroglial swelling and brain edema. PGE2 administration significantly (p less than 0.02) inhibited the progression of both brain edema and brain tissue swelling when compared with saline injected control FHF animals. However, the liver damage shown in EM assessment appeared to progress after PGE2 injection. This would appear that PGE2 is acting directly on the Blood Bain Barrier (BBB) to preserve it despite progressive hepatic failure.

Animals↗
PubMed1987

Effect of membrane thickness of collodion coated activated charcoal on adsorption of small and middle molecules.

Different thicknesses of a cellulose nitrate (CN) coating were applied to petroleum pitch bead activated charcoal. The effect of this on the adsorption of small and middle molecules in vitro was studied. This was done by measuring the rate of adsorption of Vitamin B12, creatinine and uric acid from aqueous solution by activated charcoal having CN coatings of varying thickness (0.1% to 4.0% by weight). A CN coating weight of up to 0.2% caused negligible or no decrease in the rate of adsorption of all three solutes as compared with uncoated charcoal. Coating weights greater than 0.2% caused a significant decrease in the rate of adsorption of Vitamin B12, and uric acid but had little effect on the rate of adsorption of creatinine. Coating weights greater than 1.8% caused a significant decrease in the rate of adsorption of creatinine.

Adsorption↗
PubMed1987

Applications of artificial cells in medicine and biotechnology.

This article summarizes those research activities in the area of artificial cells which are related to medicine and biotechnology. This includes the applications of artificial cells in: (1) chronic renal failure, (2) drug poisoning, (3) aluminium and iron removal, (4) fulminant hepatic failure, (5) immunosorbent for direct blood perfusion, (6) enzyme therapy and metabolic function replacement, (7) immobilized cell cultures for Bioartificial Organs, (8) blood substitutes, (9) microencapsulation, (10) biotechnology and other areas.

Artificial Organs↗
PubMed1987

Conversion of urea or ammonia into essential amino acids (L-leucine, L-valine, and L-isoleucine) using multienzyme systems and NADH-dextran immobilised in artificial cells.

Artificial cells containing leucine dehydrogenase (EC 1.4.1.9), alcohol dehydrogenase (EC 1.1.1.1; or glucose dehydrogenase, EC 1.1.1.47; or lactic dehydrogenase, EC 1.1.1.27; or malic dehydrogenase, EC 1.1.1.37), urease (EC 3.5.1.5) and dextran-NAD+ were prepared. Ammonia or urea could be converted into L-leucine, L-valine and L-isoleucine using artificial cells with four different multienzyme systems.

Amino Acids, Essential↗
PubMed1987

Flow analysis for optimal configuration of hemoperfusion device.

The objective of this experiment was to determine the flow characteristics of a hemoperfusion device. The standard device consists of a cylindrical container which is tapered towards the outlet end. Flow enters the column through a small inlet tube into the wide frontal area of the column. Having passed through the column containing collodian coated activated charcoal spheres, it leaves by the tapered outlet. In order to achieve our aim, we designed and built a two-dimensional plexiglass model consisting of a vertical cross section of the actual hemoperfusion device. Glass beads were used to simulate the artificial carbon cells and a colored solution was used to enable us to visualize the flow. In the normal configuration, it was determined that stagnation and channelling were present. The model was then analysed in the inverse configuration. This way, flow inlet is through the tapered end and flow outlet is towards the wider cylindrical end. This inverse flow configuration improved the flow characteristics and eliminated most of the channelling and stagnation.

Biomedical Engineering↗
PubMed1987

Orally ingested microencapsulated urease and an adsorbent, zirconium phosphate, to remove urea in kidney failure.

Dialysis is the conventional treatment for chronic renal failure. It is cumbersome, expensive and time-consuming and thus alternate treatments have long been sought. A compact system consisting of haemoperfusion in series with ultrafiltration can nearly replace dialysis. A urea removal system is the only step required to complete this approach. The potential of combining a microencapsulated enzyme, urease, with an ammonium ion adsorbent, zirconium phosphate, to remove urea was examined in vitro. Urease converts urea to ammonium ions which are then adsorbed onto zirconium phosphate. This combination would be most effective in the intestinal tract. The capacity of zirconium phosphate is probably not enough to effect the removal of enough urea to completely replace dialysis in patients with no renal function. However, this system could potentially 1) delay the onset of dialysis therapy in patients who still have some renal function, either alone or in combination with haemoperfusion-ultrafiltration, or 2) reduce dialysis treatment times.

Adsorption↗
PubMed1986

Phenylalanine ammonia-lyase immobilized in microcapsules for the depletion of phenylalanine in plasma in phenylketonuric rat model.

Microencapsulation of the enzyme phenylalanine ammonia-lyase was developed for in vivo depletion of systemic phenylalanine in phenylketonuric rats. Compared to normal rats, systemic phenylalanine blood levels in phenylketonuric rats was increased by 15-20-fold. Daily oral administration of 1 unit of phenylalanine ammonia-lyase-loaded artificial cells to phenylketonuric rats lowered the systemic phenylalanine level to 58% +/- 18% (mean + S.D.) in 7 days (P less than 0.010), while 5 units lowered the systemic phenylalanine level to 25% +/- 8%. 5 units of the immobilized enzyme lowered the systemic phenylalanine level to normal levels within 6 days. Phenylketonuric treated rats showed no signs of abnormal behavior and weight loss compared to phenylketonuric non-treated rats. The immobilized enzyme within artificial cells is therefore protected against low gastrointestinal pH and proteolytic enzymes.

Ammonia-Lyases↗
PubMed1986

Release of cholecystokinin and exocrine pancreatic secretion in response to an elemental diet in human subjects.

We investigated in human volunteers the effects of an elemental diet (ED) containing amino acids on release of endogenous cholecystokinin (CCK) using a highly sensitive and specific radioimmunoassay of CCK and exocrine pancreatic secretion using a dye dilution technique with polyethylene glycol 4000 as a nonabsorbable marker. Intrajejunal administration of ED at three different infusion rates (12.5, 25, and 50 ml/30 min) resulted in a significant increase in plasma CCK concentration in a dose-related manner. Plasma concentrations of gastrin or secretin, however, did not change. Pancreatic secretion of protein, amylase, and bicarbonate also increased significantly. The change in pancreatic secretion of protein, amylase, and bicarbonate output paralleled that of the circulating CCK level but not that of plasma secretin. Thus, the dose of amino acid contained in ED recommended for clinical use can significantly stimulate the release of CCK from the upper small intestine, raising the plasma concentration of CCK. This level can evoke a significant increase in exocrine pancreatic secretion.

Adult↗
PubMed1986

Lipid-polyamide-polyethyleneimine microcapsules for immobilization of free cofactors and multienzyme system.

Lipid-polyamide membrane microcapsules containing multienzyme system convert ammonia into glutamate. L-Glutamic dehydrogenase, alcohol dehydrogenase, NAD+, and alpha-ketoglutarate retained within the microcapsules do not leak out. This way the multienzyme system can recycle the free cofactor NAD+ and synthesize glutamate from external lipophilic ammonia diffusing into the microcapsules. By using polyethyleneimine instead of hemoglobin as microcapsule filler it is possible to obtain higher conversion rates and to increase the storage stability of the recycling activity.

Alcohol Dehydrogenase↗