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Biomedical subjects

T M Chang

Publications and source records attributed to T M Chang.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cellular mechanism of sodium oleate-stimulated secretion of cholecystokinin and secretin.

Long-chain fatty acids are potent stimulants of secretin and CCK release. The cellular mechanisms of fatty acid-stimulated secretion of these two hormones are not clear. We studied the stimulatory effect and mechanism of sodium oleate (SO) on secretin- and CCK-producing cells. SO stimulated the release of secretin or CCK from isolated rat mucosal cell preparations enriched in either secretin- or CCK-producing cells, respectively. SO also time- and dose-dependently stimulated secretin and CCK release from STC-1 cells. In STC-1 cells, SO-stimulated secretin and CCK release was potentiated by IBMX and inhibited by a protein kinase A-selective inhibitor and a cAMP-specific antagonist. SO-stimulated releases of the two hormones were also inhibited by downregulation or inhibitors of protein kinase C, a calmodulin antagonist and an inhibitor of calmodulin-dependent protein kinase II. Chelating of extracellular Ca(2+) or addition of an L-type calcium channel blocker diminished SO-stimulated hormone releases. SO caused an increase in intracellular Ca(2+) concentration that was partially reversed by diltiazem but had no effect on production of cAMP, cGMP, or inositol-1,4,5-triphosphate. These results indicate that SO acts on secretin- and CCK-producing cells. Its stimulatory effect is potentiated by endogenous protein kinase A and mediated by activation of Ca(2+) influx through the L-type channels and of protein kinase C and Ca(2+)/calmodulin-dependent protein kinase II.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Artificial cell biotechnology for medical applications.

Artificial cells are prepared in the laboratory for medical and biotechnological applications. The earliest routine clinical use of artificial cells is in the form of coated activated charcoal for hemoperfusion. Implantation of encapsulated cells are being studied for the treatment of diabetes, liver failure and the use of encapsulated genetically engineered cells for gene therapy. We recently found that daily orally administered artificial cells containing a genetically engineered microorganism can lower the elevated urea level in uremic rats to normal levels and increase the survival of the animal. Furthermore, this can remove potassium, phosphate, uric acid and other waste metabolites from uremic plasma. Blood substitutes based on modified hemoglobin are already in phase-III clinical trials in patients with as much as 20 units infused into each patient during trauma surgery. Artificial cells containing enzymes are being developed for clinical trials in hereditary enzyme deficiency diseases and other diseases. Artificial cells are also being investigated for drug delivery and other uses in biotechnology, chemical engineering and medicine.

Animals↗
PubMed2000

Artificial cells microencapsulated genetically engineered E. coli DH5 cells for the lowering of plasma creatinine in-vitro and in-vivo.

High level of plasma creatinine occurs in renal insufficiency, uremia, and other diseases. At present lowering of this metabolite is done by using dialysis and other techniques. In this article, we report the use of artificial cells microencapsulated genetically engineered E. coli DH5 cells for lowering plasma creatinine in-vitro and in-vivo. Result shows that artificial cells were able to lower plasma creatinine in-vitro from 21.80 +/- 1.10 mg/dl to 21.80 +/- 1.10 mg/dl in 60 minutes and to 19.34 +/- 0.60 mg/dl in 3 hours. Result also shows that when given orally on a daily basis, artificial cells microencapsulated genetically engineered E. coli DH5 cells were also able to lower plasma creatinine in rats.

Animals↗
PubMed2000

Effects of bone marrow cells on hepatocytes: when co-cultured or co-encapsulated together.

Bone marrow cells co-cultured with hepatocytes resulted in hepatocytes that can be maintained in culture for 14-21 days. This is compared to 7-10 days with hepatocytes alone under the same conditions. Similarly, when bone marrow cells are co-encapsulated together with hepatocytes, the viability of hepatocytes in culture medium is prolonged to 28 days. This is compared to 14 days when hepatocytes are encapsulated alone under the same conditions. These results suggest that bone marrow cells can contribute to the viability and maintenance of hepatocytes. It addition, this principle could be applied to other situation as in helping the regeneration of hepatocytes in liver failure and also for other cells and organs.

Animals↗
PubMed2000

Sustained drug release characteristics of biodegradable composite poly(d,l)lactic acid-poly(l)lactic acid microcapsules containing ciprofloxacin.

Ciprofloxacin polylactic microcapsules were prepared by the phase separation process. Two types of polylactic acid, poly(d,l)lactic acid and poly(l)lactic acid were combined as membrane materials to prevent the aggregation which happened frequently in the phase separation process. The polymer compositions of the microcapsules can influence the release rate of Ciprofloxacin. The optimal release rate of the drug can be obtained by modifying microcapsule compositions. Poly(d,l)lactic acid is superior in slowing the rate of drug release than poly(l)lactic acid. However, poly(l)lactic acid is necessary in the preparation of the microcapsules to prevent aggregation.

Anti-Infective Agents↗
PubMed2000

In vitro and in vivo uric acid lowering by artificial cells containing microencapsulated genetically engineered E. coli DH5 cells.

Increase in systemic uric acid occurs in renal insufficiency, gout, chemotherapy, and other diseases. Dialysis can lower this metabolite but is expensive. The use of drugs can, sometime, result in side effects. Therefore, a suitable affordable method for this is required. In this article, for the first time, we report the use of artificial cells containing micro encapsulated genetically engineered E. Coli DH5 cells for lowering uric acid in vitro and in vivo. Results show that this novel approach has the ability to significantly lower uric acid from 84.80 +/- 3.40 mg/dl to 9.32 +/- 0.05 mg/dl in vitro and from the plasma of the experimental animals from the control levels of 71.00 +/- 27.49 mg/dl to 20.33 +/- 17.92 mg/dl in vivo. Continued daily oral administration maintained the plasma uric acid concentration of experimental uremic rats to the normal plasma uric acid level range during the entire test period.

Animals↗
PubMed1999

Artificial cells, encapsulation, and immobilization.

The basic principles of artificial cells, encapsulation and immobilization form the basis for a number of bioartificial organs. Hemoperfusion based on encapsulated adsorbent has been in routine clinical uses for many years to remove toxins or drugs from the circulating blood. Blood substitutes based on crosslinked hemoglobin or encapsulated hemoglobin are being developed and tested in phase II and Phase III clinical trials. Enzyme therapy using microencapsulated enzymes have been studied in animal studies and in a preliminary human study. Encapsulation or other ways of immobilization of cells are being developed extensively by many groups. This includes the encapsulation or immobilization of islets, hepatocytes and genetically engineered cells.

Animals↗
PubMed1999

Porcine pancreatic phospholipase A2 stimulates secretin release from secretin-producing cells.

We have isolated, from canine pancreatic juice, two 14-kDa proteins with secretin-releasing activity that had N-terminal sequence homology with canine pancreatic phospholipase A2 (PLA2). In this study we have obtained evidence that secretin-releasing activity is an intrinsic property of pancreatic PLA2. Porcine pancreatic PLA2 from Sigma or Boehringer Mannheim was fractionated into several peaks by reverse phase high performance liquid chromatography. They were tested for stimulation of secretin release from murine neuroendocrine intestinal tumor cell line STC-1 and secretin cells enriched mucosal cell preparations isolated from rat upper small intestine. Each enzyme preparation was found to contain several components of secretin-releasing activity. Each bioactive fraction was purified to homogeneity by rechromatography and then subjected to mass spectral analysis and assays of PLA2 and secretin-releasing activities. It was found that the fraction with highest enzymatic activity also had the highest secretin-releasing activity and the same Mr as porcine pancreatic PLA2. Moreover, it also had the same N-terminal amino acid sequence (up to 30 residues determined) as that of porcine pancreatic PLA2, suggesting that it was identical to the enzyme. Purified porcine pancreatic PLA2 also stimulated secretin release concentration-dependently from both STC-1 cells and a mucosal cell preparation enriched in secretin-containing endocrine cells isolated from rat duodenum. Abolishment of the enzymatic activity by pretreatment with bromophenacyl bromide did not affect its secretin-releasing activity. The stimulatory effect of purified pancreatic PLA2 on secretin secretion from STC-1 cells was inhibited by an L-type Ca2+ channel blocker, by down-regulation of protein kinase C or by pretreatment of the cell with pertussis toxin. It is concluded that porcine pancreatic PLA2 possesses an intrinsic secretin-releasing activity that was independent of its enzymatic activity. This action is pertussis toxin-sensitive and is in part dependent on Ca2+ influx through the L-type channel and activation of protein kinase C.

Animals↗
PubMed1999

A different approach to treatment of phenylketonuria: phenylalanine degradation with recombinant phenylalanine ammonia lyase.

Phenylketonuria (PKU), with its associated hyperphenylalaninemia (HPA) and mental retardation, is a classic genetic disease and the first to have an identified chemical cause of impaired cognitive development. Treatment from birth with a low phenylalanine diet largely prevents the deviant cognitive phenotype by ameliorating HPA and is recognized as one of the first effective treatments of a genetic disease. However, compliance with dietary treatment is difficult and when it is for life, as now recommended by an internationally used set of guidelines, is probably unrealistic. Herein we describe experiments on a mouse model using another modality for treatment of PKU compatible with better compliance using ancillary phenylalanine ammonia lyase (PAL, EC 4.3.1.5) to degrade phenylalanine, the harmful nutrient in PKU; in this treatment, PAL acts as a substitute for the enzyme phenylalanine monooxygenase (EC 1.14.16.1), which is deficient in PKU. PAL, a robust enzyme without need for a cofactor, converts phenylalanine to trans-cinnamic acid, a harmless metabolite. We describe (i) an efficient recombinant approach to produce PAL enzyme, (ii) testing of PAL in orthologous N-ethyl-N'-nitrosourea (ENU) mutant mouse strains with HPA, and (iii) proofs of principle (PAL reduces HPA)-both pharmacologic (with a clear dose-response effect vs. HPA after PAL injection) and physiologic (protected enteral PAL is significantly effective vs. HPA). These findings open another way to facilitate treatment of this classic genetic disease.

Animals↗
PubMed1999

Thoracic epidural anesthesia for pain relief and postoperation recovery with modified radical mastectomy.

The purpose of this study was to investigate whether thoracic epidural anesthesia (TEA) provides better postoperative pain relief and recovery than general anesthesia (GA) for modified radical mastectomy (MRM) surgery. Sixty-four patients rated as American Society of Anesthesiologists (ASA) 1 to 3 who underwent MRM surgery were included in the study. In TEA group patients, 2% lidocaine (15-20 ml) was administered via the epidural route as primary anesthesia, in conjunction with midazolam (5-10 mg) and fentanyl (<250 microg) for amnesia. The GA patients were maintained with isoflurane and 50% nitrous oxide in oxygen. After operation the patients were given pethidine (1 mg/kg IM) as required for pain relief. The time to first pethidine requirement, total pethidine consumption, worst pain score, bed rest time, satisfaction score, and anesthesia-related side effects were recorded for 2 days after surgery. The results show that TEA provided a more prolonged analgesic effect than GA after operation. A longer time to first pethidine requirement (19.2 +/- 1.5 vs. 7.6 +/- 2.5 hours) (p < 0. 001) and decreased pethidine consumption (17.2 +/- 7.0 vs. 76.3 +/- 17.4 mg) (p < 0.001) were observed in the TEA group than in the GA group, respectively. A worse visual analog scale (VAS) pain score was observed in the GA group (5.7 +/- 0.6) than in TEA patients (4.3 +/- 0.4) (p < 0.01). The average bed rest time was significantly shorter in the TEA group (16.9 +/- 0.9 hours) (p < 0.01) than in the GA group (27.1 +/- 4.1 hours). Overall satisfaction scores were significantly higher in the TEA group (4.4 +/- 0.1) (p < 0.01) than in the GA group (3.5 +/- 0.2). Side effects were observed at a higher frequency in the GA group (16/32) (p < 0.0001) than in the TEA group (3/32). The frequency of pethidine injection for pain relief was significantly lower in the TEA group (8/32) (p < 0.0001) than in the GA group (24/32). The total hospital cost (NT 64,392 +/- 3,523 vs. NT 53,806 +/- 2,817) (p = 0.0342) and anesthesia cost (NT 7,968 +/- 246 vs. NT 5,268 +/- 262) (p < 0.0001) are also significantly lower in the TEA group than the GA group. In conclusion, TEA provided better postoperative pain relief and recovery and lower cost than GA for MRM surgery.

Analgesics, Opioid↗
PubMed1999

Future prospects for artificial blood.

Concern about potential infective agents in donated blood has stimulated the recent development of blood substitutes. Chemically cross-linked hemoglobins are already undergoing clinical trials and might soon be ready for routine use. New generations of modified hemoglobin are being prepared to modulate the effects of nitric oxide and oxygen radicals, and artificial red blood cells are also under development.

Biodegradation, Environmental↗
PubMed1999

Purification of two secretin-releasing peptides structurally related to phospholipase A2 from canine pancreatic juice.

We previously showed that canine pancreatic juice contains a secretin-releasing factor activity. In this study, we carried out isolation of two secretin-releasing peptides (SRPs) from canine pancreatic juice. Through ultrafiltration, anion and cation exchange, and reverse-phase high-performance liquid chromatography (HPLC) steps and an in vitro bioassay in STC-1 cells, two SRPs, SRP-1 and SRP-2, were isolated and purified to homogeneity. Both SRPs dose-dependently stimulated secretin release from STC-1 cells. The results of mass spectral analysis indicated that SRP-1 and SRP-2 had molecular masses of 14,061 Da and 14,053 Da, respectively. N-terminal amino acid sequence analysis indicated that SRP-1 was identical to canine pancreatic PLA2 in the 25 residues determined; whereas SRP-2 had 71% sequence homology to the enzyme in the first 21 residues. Commercially available porcine pancreatic PLA2 dose-dependently stimulated secretin release from STC-1 cells. Porcine pancreatic PLA2 also stimulated secretin release from a secretin-producing cells-enriched preparation isolated from rat duodenal mucosa. These results suggest that pancreatic PLA2 and its related peptide may participate in regulation of secretin secretion.

Amino Acid Sequence↗
PubMed1999

Vagus nerve modulates secretin binding sites in the rat forestomach.

Secretin is well known for its inhibitory action on gastric motility. It has been reported that secretin in a physiological dose inhibits gastric motility through mediation by the vagal afferent pathway. Secretin also elicited relaxation of carbachol-stimulated rat forestomach muscle strips by binding to its receptors, suggesting a direct action on this peripheral tissue. We hypothesized that vagal input may affect the action of secretin by modulating the level of secretin receptor in the forestomach. Several treatments, including vagal ligation, vagotomy, perivagal application of capsaicin or colchicine, intravenous infusion of tetrodotoxin, and intraperitoneal injection of atropine, were performed to investigate their effects on secretin receptor binding to forestomach membranes. Specific binding of 125I-labeled secretin to forestomach membranes was significantly decreased (45%) by vagal ligation, vagotomy (50%), or perivagal colchicine treatment (40%). On the contrary, specific binding of 125I-secretin was not affected by perivagal capsaicin treatment, intravenous infusion of tetrodotoxin, or intraperitoneal injection of atropine. By Scatchard analysis of the binding data, the capacity of the high-affinity binding sites in forestomach membranes was found to decrease significantly after vagal ligation compared with membranes from the sham-operated group. However, the affinity at the high-affinity binding sites, the binding parameters of the low-affinity binding sites, and binding specificity were not changed. Vagal ligation but not perivagal capsaicin treatment reduced the inhibitory effect of secretin on bethanechol-stimulated contraction of isolated forestomach muscle strips, causing a right shift in the dose-response curve. These results suggest that vagal input through axonal transport plays a significant role on secretin action by modulating the capacity of secretin binding sites (but not affinity or specificity), at least in rat forestomach.

Animals↗
PubMed1999

Biodegradable polylactic acid nanocapsules containing ciprofloxacin: preparation and characterization.

Nanocapsules have been studied as carriers to deliver different types of drugs into macrophages. Many studies have shown that the nanocapsules can enhance the biological response of the drugs. In this study, we prepared ciprofloxacin nanocapsules with polylactic acid. The ciprofloxacin is an antibacterial agent. The ciprofloxacin nanocapsules prepared have a means diameter of 168 nm. In phosphate buffer at pH 7.4, high encapsulation rate was obtained. The nanocapsules with high encapsulation rate can also be made from ciprofloxacin base.

Biodegradation, Environmental↗
PubMed1999

Growth kinetics of genetically engineered E. coli DH 5 cells in artificial cell APA membrane microcapsules: preliminary report.

This paper describes the growth kinetics of genetically engineered E. coli DH5 cells inside the APA membrane artificial cells. The APA microcapsule membrane found does not significantly affects the growth of the encapsulated E. coli DH5 cells. The total protein production of the E. coli DH5 cells inside the APA microcapsules were not significantly different from that of the bacterial cells grown in the free bacterial media. The result also show that the log phase APA artificial cells containing genetically engineered E. coli DH5 would be highly effective for the conversion of various external metabolites.

Alginates↗
PubMed1999

Kinetic studies of hepatocyte UDP-glucuronosyltransferase: evidence of an allosteric enzyme.

The kinetic analysis of the enzyme UDP-glucuronosyltransferase (UDPGT) responsible for the conjugation of bilirubin, suggest that it is a multisubunit enzyme in which there is cooperative binding of substrate to the subunits. The binding of bilirubin to UDP-glucuronosyltransferase shows positive cooperativity with an apparent dissociation constant of 7.824 x 10(-4) +/- 6.405 x 10(-4) mM. The apparent Hill coefficient for bilirubin to UDPGT is 2.9. The binding of UDP-glucuronic acid exhibits kinetics with mixed cooperativity. Analysis with the Hill equation give an apparent dissociation constant of 6.873 +/- 3.816 mM and a Hill coefficient of 4.028 +/- 1.045. These values of the Hill coefficient are consistent with an enzyme being an oligomer with 6 subunits, since the actual number of subunits must be greater than the apparent Hill coefficient.

Allosteric Regulation↗
PubMed1999

Comparison of bilirubin conjugation in encapsulated hepatocytes, hepatocyte homogenate and intact hepatocytes.

Homogenized rat hepatocytes, whole hepatocytes and encapsulated hepatocytes were incubated with bilirubin and UDP-glucuronic acid to test their ability to form bilirubin conjugates. Bilirubin monoconjugated and diconjugated were detected in all the three preparations by HPLC analysis. The UDP-glucuronosyltransferase (UDPGT) activity of homogenized hepatocytes was 0.002 +/- 0.00006 mM/min per million cells; that of intact hepatocytes was 0.001 +/- 0.00006 mM/min per million cells and that of encapsulated hepatocytes was 0.0005 +/- 0.00002 mM/min per million cells.

Alginates↗