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Biomedical subjects

T M Chang

Publications and source records attributed to T M Chang.

At least 379 records · Page 21Linked to original sources
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Induction chemotherapy for advanced head and neck cancers: a literature review.

Induction chemotherapy before surgery and/or radiotherapy for previously untreated head and neck carcinoma results in greater response rates than chemotherapy for recurrent head and neck carcinomas. Its theoretical advantages are presented. Most studies using induction chemotherapy are nonrandomized, uncontrolled pilot efforts. Multiple-drug regimens result in greater response rates than single agents, and multiple courses result in greater response rates than single courses. Prognostic factors are discussed. Toxicities are tolerable, except for several reported regimens combining cisplatin, bleomycin, and methotrexate. Induction chemotherapy for head and neck cancer is promising and needs further studies with controlled, randomized trials with long-term follow-up.

Antineoplastic Agents↗
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Cholinergic role on release and action of motilin.

In conscious dogs with gastric fistula and platinum electrodes on the antrum, duodenum and jejunum, IV atropine 100 micrograms/kg/hr and hexamethonium 10 mg/kg/hr, blocked cyclic increases in fasting plasma motilin concentration (PMC) and spontaneous migrating myoelectric complexes (MMCs) of both antrum and duodenum. The two drugs also blocked occurrence of premature MMCs produced by synthetic porcine motilin. In anesthetized dogs, electrical stimulation of cervical vagi with stimulation parameters: 9 V, 10 c/s, 5 msec, caused a significant increase in both portal and femoral venous PMC which was blocked by atropine. Fractionations of vagus nerve extracts by gel filtration using Sephadex G-50 superfine column revealed most of motilin-like immunoreactivity (MLI) with the same mobility as pure porcine motilin. Studies suggest that cholinergic influence plays a significant role on release of motilin.

Animals↗
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Presence of biologically and immunologically active secretin-like substance in the mammalian brain.

The present study involves the isolation and characterization of secretin-like immunoreactivity from the brains of pigs, rats and dogs. Secretin-like immunoreactivity was extracted with 0.1 N HCl and subjected to SP-Sephadex ion exchange chromatography and gel filtration on a Sephadex G-50 superfine column. The average amounts of secretin-like immunoreactivity in the extracts of 2 pigs, 7 rats and 6 dog brains were 0.25 ng/g, 2.4 +/- 0.2 ng/g and 0.34 +/- 0.07 ng/g fresh tissue weight, respectively. The secretin-like immunoreactivities in the brain extracts exhibited the same retention coefficient as natural porcine secretin on gel filtration and were eluted in the same salt gradient from the SP-Sephadex column. A partially purified secretin-like immunoreactivity isolated from canine brain exhibited the same bioactivity as natural porcine secretin to stimulate pancreatic volume flow in anesthetized rats (n = 4). These results indicated that secretin-like immunoreactivities from brain extracts possess the same molecular size and charge as natural porcine secretin and the secretin-like immunoreactivity isolated from dog brain is active in stimulating pancreatic secretion in anesthetized rats.

Animals↗
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The effect of cyclic nucleotides on secretin secretion in canine duodenal mucosa in vitro.

We examined the effects of cyclic nucleotides and calcium on secretin release from canine duodenal mucosal explants incubated in organ culture media. Time course studies revealed that at pH 7.4, 5 and 10 mM dibutyryl cyclic adenosine monophosphate (DBcAMP) increased secretin release progressively, reaching a peak at 2 hours. Two mM of DBcAMP at pH 7.4 did not increase secretin release but at pH 4.5, all 3 doses potentiated secretin release. DBcAMP-stimulated secretin release was not dependent on the influx of extracellular calcium. Graded doses of 3-isobutyl-1-methylxanthine (IBMX) did not stimulate secretin secretion but 1 mM IBMX with 2 mM DBcAMP increased secretin secretion significantly. Dibutyryl cyclic guanosine monophosphate, cholera toxin and 5'-guanylyl-imidodiphosphate (GPP(NH)p) did not stimulate basal secretion release. The release of secretin from our explants incubated at pH 7.4 was not due to specific leakage because all of our viability studies revealed that our explants were functionally intact at the end of 2 hours. Our observations suggest that cyclic nucleotides may participate in the intracellular regulation of secretin secretion.

1-Methyl-3-isobutylxanthine↗
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Differences in gastric emptying between highly selective vagotomy and posterior truncal vagotomy combined with anterior seromyotomy.

Gastric emptying has been reported to be both delayed and unchanged following posterior truncal vagotomy combined with anterior seromyotomy (PTV + AS). When compared to highly selective vagotomy (HSV), our clinical experience was that PTV + AS not uncommonly produced postprandial distress. We studied gastric emptying of both liquids and solids 3 and 12 months following HSV and PTV + AS to determine what if any differences there were in gastric emptying between the two procedures. We compared these results with those from studies done in both normal subjects and unoperated duodenal ulcer patients. In 26 duodenal ulcer patients with perforation (n = 18) or bleeding (n = 8), who were treated with HSV (n = 10) or PTV + AS (n = 16), gastric emptying of liquids and solids was evaluated at 3 months and 12 months postoperatively. At 3 months, gastric emptying of liquids was delayed in both the HSV and PTV + AS groups as compared to values in both normal subjects and unoperated duodenal ulcer patients. The emptying of solids was markedly delayed by PTV + AS in contrast to HSV at 3 months (167.1 +/- 28.4 minutes vs. 79.9 +/- 16.7 minutes; P <0.05). The lag duration was not affected. A limited number of patients studied at 12 months showed similar and near-normal emptying of solids in both the HSV and PTV + AS groups (67.5 +/- 7.0 minutes vs. 70 +/- 6.6 minutes). PTV + AS in contrast to HSV produces more marked delayed emptying of liquids and solids at 3 months; with time (1 year) these values return to near normal.

Gastric Emptying↗
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Control release of prostaglandin E2 from polylactic acid microcapsules, microparticles and modified microparticles.

Low molecular weight polylactic acid (PLA) microparticles containing prostaglandin E2 were prepared. An average particle size of 30 micron was obtained by grinding at low temperature. These particles were further treated by heating to modify the shape and the release pattern. Microscopic studies showed that the modified particles had a smoother surface than the non-modified particles. The drug was also incorporated into PLA microcapsules using the solvent evaporation process, but the incorporation efficiency was lower. We studied the release profiles of modified particles prepared using different molecular weight PLA. The release rate depended on the molecular weight with lower molecular weights having a greater release rate. In addition, the release studies showed different matrix forms made from the same molecular weight PLA had different release patterns. For example, the microcapsules released the drug very slowly whereas the modified particles exhibited a moderate release rate. It was also noted that the matrix release model could describe the release patterns of microcapsules and modified particles very well. However, the release patterns of non-modified microparticles did not follow this model.

Capsules↗
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Preparation of polylactic acid microcapsules containing ciprofloxacin.

Microcapsules have been used as drug delivery systems in the pharmaceutical field for sustained or controlled release of drug, and for artificial cells and organs. Biodegradable polymers, especially polylactic acid, have been widely used in this field. In this study, an attempt was made to develop a new method to prepare polylactic acid microcapsules for drug delivery. The biodegradable polylactic acid microcapsules were made by the phase separation process: two types of polylactic acid, poly[(D,L)lactic acid] and poly[(L)lactic acid] were combined as the membrane material. Because of the difference of the crystal properties of the two polymers, the aggregation which happens frequently in the phase separation process was prevented. As a model drug, Ciprofloxacin was encapsulated in the polylactic acid microcapsules.

Anti-Infective Agents↗
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Adsorption of chitin derivatives onto liposomes: optimization of adsorption conditions.

A 2(4) factorial design is used to optimize the adsorption conditions of the hydrophilic anionic polyelectrolytes. Carboxymethylchitin (CMC) and Carboxymethyl/Glycolchitin (CO) onto liposomes at physiological ionic strength (I) and pH using phosphate buffered saline (PBS, I = 154 mM, pH = 7.4). Positive ([+]) or high surface affinity liposomes (DSPC:CHOL:DMTAP, 5:4:1), and Neutral ([N]) or low surface affinity liposomes (DSPC:CHOL, 1:1) were used as adsorption surfaces. Results of the calculations of the main effects indicate that polymer molecular weight (mwt), Surface Affinity (S), Number of Adsorption Shots (Sh), Temperature (T), and the combinations mwt x S, mwt x Sh are the most important process parameters. Results of a study conducted at T = 37 degrees C show that no loss occurs from the positive surface at the highest particle concentration, Np = 4.043 x 10(11). Finally, the extent of polymer-induced particle aggregation is decreased when the diameter of the uncoated liposomes is doubled from 0.22 to 0.45 micron. These results are as expected, given the stiffness and the dimensions of the macromolecules.

Adsorption↗
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In-vivo degradation of poly(lactic acid) of different molecular weights.

Lactic acid was polymerized using tetraphenyl tin as a catalyst. The molecular weight of the resultant poly(lactic acid) varied between 0.89 X 10(6) and 2.94 X 10(6) depending upon the concentration of the catalyst used. In-vivo degradation of the poly(lactic acid) samples having 4 different molecular weights were studies by implanting these in Wistar rats. It was found that at the end of a 48-week implantation period lower molecular weight poly(lactic acid) samples were degraded at a faster rate than the higher molecular weight samples.

Animals↗
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Plasma/intestinal concentration patterns suggestive of entero-portal recirculation of amino acids: effects of oral administration of asparaginase, glutaminase and tyrosinase immobilized by microencapsulation in artificial cells.

This study suggests the presence of an entero-portal recirculation of amino acids. Endogenous sources of amino acids are secreted at high concentration into the small intestine. Most of the amino acids are absorbed as the content passes down the small intestine. Plasma amino acid concentrations are on the average only 1-5% of the concentrations in the duodunum. This is true even in rats on 24 hours of water and sugar with no exogenous sources of amino acids. For example, the PLASMA:DUODENUM concentrations (mumole/litre) are: Asparagine 37:7164, Tyrosine 94:9579, and glutamine/histidine 409:9708. This entero-portal recirculation of amino acids means the potential of a method for specific depletion of body amino acids by oral ingestion of bioreactants like immobilized enzymes. Preliminary studies used artificial cells to immobilize asparaginase,glutaminase and tyrosinase by microencapsulation. Six hours after 1 oral administration, asparagine, glutamine and tyrosine in the ileum were lowered to 10% of the level of the control. Artificial cells containing no enzymes were used as the control.

Administration, Oral↗
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Reduction of hydroxyl radical generation in a rat hindlimb model of ischemia-reperfusion injury using crosslinked hemoglobin-superoxide dismutase-catalase.

The effects of PolyHb (intermolecularly crosslinked hemoglobin) and PolyHb-SOD-CAT (intermolecularly crosslinked hemoglobin, superoxide dismutase and catalase) on the production of hydroxyl radical was studied using a rat hindlimb model of ischemia-reperfusion. Hydroxyl radical generation was assessed by an indirect assay based on the hydroxylation of 4-hydroxybenzoate. The hydroxylation product, 3,4 dihydroxybenzoate (3,4 DHBA), was analyzed by high performance liquid chromatography and electrochemical detection. The identification of 3,4 DHBA was confirmed by analysis of authentic standard and an in vitro hydroxyl radical generation system. Ischemia was induced in both hindlimbs by ligation of the infrarenal aorta. After a 4hr ischemic period, hindlimbs were simultaneously perfused with PolyHb-SOD-CAT (5 g/dl) into one limb and PolyHb (5 g/dl) into the other limb via femoral arterial catheters. Each perfusate also contained the hydroxyl radical trap, 4-hydroxbenzoate (5 mM). Femoral venous effluents were analyzed for the presence of the 3,4 DHBA. Data indicates that greater 3,4 DHBA production occurs during PolyHb perfusion as compared to PolyHb-SOD-CAT. These preliminary results show that perfusion with PolyHb-SOD-CAT may alleviate oxidative stress in a model of ischemia-reperfusion.

Animals↗
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Crosslinked hemoglobin-superoxide dismutase-catalase scavenges free radicals in a rat model of intestinal ischemia-reperfusion injury.

An in vivo rat model of isolated intestinal ischemia-perfusion was developed. This is used to compare the effects of crosslinked hemoglobin (PolyHb) versus crosslinked hemolobin-superoxide dismutase-catalase (PolyHb-SOD-CAT) on free radical generation in ischemia-reperfusion. Fasted, anesthetized male Sprague Dawley rats underwent midline laparotomy with cannulation of the abdominal aorta and inferior vena cava. Ligation was carried out at the renal pedicles bilaterally and the aorta and vena cava proximally at the diaphragm and distally above the femoral bifurcation. The system was flushed of blood with 20 ml of lactated Ringer's solution. The portal vein was then cannulated with distal clamping at the porta hepatis so that isolated intestinal perfusion could be achieved with the aorta as the inlet and the portal vein as the outlet. Following a 90 minute ischemic time, perfusates containing modified hemoglobin (5 g/dl) and 4-hydroxybenzoate (5 mM) were infused at 0.8 ml/min for 10 min. Portal vein effluent samples were collected at 2.5 minute intervals. Hydroxyl radical generation was assessed by an aromatic hydroxylation technique with 4-hydroxybenzoate (4HB). Reaction of hydroxyl radical with 4HB produces 3,4 dihydroxybenzoate (3,4 DHBA). In the PolyHb group, the levels of 3,4-DHBA increased 10.75-13.58 x-fold above pre-perfusion values compared to 2.25-3.75 x-fold in PolyHb-SOD-CAT group. This indicates that PolyHb-SOD-CAT is effective in reducing in vivo hydroxyl radical generation following reperfusion. Since free radicals may play a major role in the pathogenesis of ischemia-reperfusion injury, this suggests a role for PolyHb-SOD-CAT as a possible protective perfusate in intestinal reperfusion injury.

Animals↗
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Artificial cell microcapsules containing genetically engineered E. coli DH5 cells for in-vitro lowering of plasma potassium, phosphate, magnesium, sodium, chloride, uric acid, cholesterol, and creatinine: a preliminary report.

Lowering of plasma Mg, P, Na, Cl, uric acid, cholesterol, and creatinine is required in renal failure and other diseases. In this preliminary report, we studied the ability of artificial cells microencapsulated genetically engineered E. coli DH5 cells in lower K, Mg, P, Na, Cl, uric acid, cholestrol, creatinine, and billirubin from plasma in-vitro. Result shows that this novel approach has the ability to significantly lower these metabolites from the plasma in-vitro.

Animals↗