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Biomedical subjects

S K Chang

Publications and source records attributed to S K Chang.

At least 55 records · Page 3Linked to original sources
PubMed1993

Transdermal iontophoretic peptide delivery: in vitro and in vivo studies with luteinizing hormone releasing hormone.

Protein and peptide drugs are not orally active. Their large molecular size and charged character make them poor candidates for passive transdermal delivery. With an applied electromotive force, these drugs can be forced through the skin to be absorbed by the systemic circulation. The present study investigates the transdermal iontophoretic delivery of a peptide hormone in an in vitro model system, the isolated perfused porcine skin flap, as well as in vivo. It is shown that with knowledge of the systemic disposition of the drug, transdermal fluxes can be utilized to accurately predict in vivo serum concentrations. It is also shown that the iontophoretically delivered hormone retains both its immunologic and biologic activity.

Administration, Cutaneous↗
PubMed1993

Effects of anatomical site and occlusion on the percutaneous absorption and residue pattern of 2,6-[ring-14C]parathion in vivo in pigs.

The effects of anatomical site and occlusion on the percutaneous absorption and residue pattern of total 14C were investigated following topical application of 2,6-[ring-14C]parathion onto four skin sites (300 micrograms/10 microCi; 40 micrograms/cm2) in weanling swine using occluded and nonoccluded dosing systems. The excretion profile was examined after iv administration. After dosing onto the abdomen, buttocks, back, and shoulder (N = 4/site), total urinary and fecal excretion (%dose) by 168 hr were, for the occluded system, 43.94 +/- 2.24, 48.47 +/- 7.85, 48.82 +/- 4.49, and 29.28 +/- 5.70%, and for the nonoccluded system, 7.47 +/- 2.16, 15.60 +/- 3.71, 25.00 +/- 8.75, and 17.41 +/- 1.76%, respectively. After iv dosing, 98.44 +/- 2.83% of the applied dose was excreted primarily via urine. The total recoveries for different sites ranged from 90.09 +/- 7.10 to 94.62 +/- 1.98% in the occluded system, 77.84 +/- 5.75 to 88.18 +/- 3.34% in the nonoccluded system, and 99.03 +/- 2.89% in the iv experiments. Time of maximal excretion rate was determined in the occluded system as abdomen (7.9 +/- 3.6 hr) < buttocks (9.4 +/- 2.6 hr) < shoulder (10.5 +/- 3.8 hr) < back (13.3 +/- 7.7 hr), but in the nonoccluded system as buttocks (11.9 +/- 3.6 hr) < shoulder (12.6 +/- 4.1 hr) < back (14.3 +/- 6.4 hr) < abdomen (16.9 +/- 7.1 hr). The percutaneous absorption from the shoulder was much lower than that from the other three sites under occluded conditions. However, if nonoccluded dosing was employed, absorption from the abdomen became the lowest, with shoulder and buttocks being similar, and the back the highest. Occlusion conceals the site difference and enhances both the extent and the rate of parathion percutaneous absorption in vivo. 14C residue pattern in tissues and dosing materials was site and dosing method dependent, all of which are factors which must be considered when assessing the risk of exposure to topically applied compounds.

Abdomen↗
PubMed1993

Electric-field-induced volume and membrane ionic permeability changes of red blood cells.

When an external electric field (EF) is applied to red blood cells (RBC's), the RBC's are observed to undergo a swelling action. The swelling may or may not lead to hemolysis, depending on the EF strength. An objective verification of this swelling is by measuring the RBC mean corpuscular volume (MCV). In this study, the RBC's were exposed to the appropriate EF strength to induce swelling, but caused minimal hemolysis. The MCV was measured. The change in the erythrocyte membrane ionic permeability as a result of the EF exposure was also determined, as an objective verification of presumed membrane conductance change concomitant with the swelling. The fluxes of cations K+, Na+, and Ca++ and anion Cl- were measured. The results showed that red cell MCV was indeed increased after EF application. The EF also altered the membrane ionic conductance to allow ions to flow down their respective concentration gradient across the membrane. Without a counterbalancing ionic pressure gradient, hemoglobin colloidal pressure inevitably drew H2O in, thus producing the observed swelling.

Calcium↗
PubMed1993

Dietary regulation of rat intestinal angiotensin-converting enzyme and dipeptidyl peptidase IV.

The small intestinal brush-border membrane contains several peptidases that are involved in the hydrolysis of dietary peptides containing proline. A high-proline (gelatin) diet was administered to one of several groups of rats to study its possible regulatory effect on levels of two prolyl peptidases, namely angiotensin-converting enzyme (ACE) and dipeptidyl peptidase IV (DPP IV). Groups of rats were maintained on isocaloric diets containing either low (4%), normal (17%), or high (50%) protein (casein) or high (50%) gelatin. After 7 days, brush-border membranes and total RNA were prepared from the small intestine. ACE activity was 3- to 10-fold higher in brush-border membranes from the gelatin group compared with the low-protein group. DPP IV exhibited a three- to sixfold increase. Immunoblot analysis of brush-border membrane-associated ACE protein indicated a six- to eightfold increase in the high-gelatin group. There was also a 1.5- to 3-fold increase in steady-state levels of ACE and DPP IV mRNA. These results suggest that a diet high in proline (gelatin) is particularly effective in increasing intestinal levels of these two enzymes.

Animals↗
PubMed1993

Molecular typing of hepatitis C virus genome from sera and liver tissues of patients with anti-HCV positive chronic liver disease.

The authors investigated the distribution of HCV genotypes in patients with various chronic liver diseases in Korea. Study population was 70 individuals, positive for second generation anti-HCV EIA, consisting of 37 cases with sporadic non-A, non-B (NANB) chronic hepatitis (CH), 12 NANB hepatocellular carcinoma, 16 post-transfusion NANB hepatitis, 4 non-B blood donors and 1 healthy family member of a patient with sporadic CH. Molecular typing was performed by RT-nested PCR with type-specific primer sets deduced from the NS-5 region of HCV. The prevalence of type II was 75.0% and type III was 25.0% in sera. In liver tissues, type II HCV was shown in 63.0%, type III HCV in 3.7% and co-infections with type II and III HCV were observed in 18.5% of 27 samples biopsied. In the sera of patients with chronic hepatitis, typing results were relatively well correlated with those in tissues (75%), but type III could not be observed. Among 12 HCC patients, type III HCV appeared only in tissues, not in sera. These results suggest that type II HCV may be the major HCV type in Korea, and co-infections with type II and-III HCV may not be rare in chronic liver diseases with HCV.

Base Sequence↗
PubMed1991

Percutaneous absorption of parathion in vitro in porcine skin: effects of dose, temperature, humidity, and perfusate composition on absorptive flux.

The effect of environmental factors on the percutaneous absorption of parathion in excised porcine skin was assessed in a flow-through diffusion cell system by varying the temperature (T), relative humidity (%RH), perfusate flow rate (F), and composition (porcine serum) at three parathion doses (4, 40, and 400 micrograms/cm2) compared to standard conditions (air temperature = 37 degrees C, perfusate temperature = 37 degrees C, %RH = 60, flow rate = 4 ml/hr, and standard bovine serum albumin medium). Parathion absorption was assessed by monitoring total radiolabeled activity appearing in the perfusate over time. High relative humidity significantly increased parathion penetration, as did two elevated temperature conditions. The effects of flow rate and perfusate composition were variable and dose dependent. In the present studies, lower applied doses appeared to be more sensitive to changes in the environmental conditions studied. These results suggest that these parameters have independent and different degrees of effect on parathion percutaneous absorption. Experimental conditions should be strictly controlled and dose-response studies need to be conducted when evaluating transdermal studies. Finally, if similar effects occur in vivo, the risk assessment calculations on percutaneous absorption should take these parameters into consideration.

Animals↗
PubMed1990

Nonuniform alteration of cis-diamminedichloroplatinum(II) tissue distribution in dogs with whole body hyperthermia.

The purpose of this study was to investigate the pharmacokinetics and tissue disposition of cisplatin (CDDP) in euthermic and hyperthermic dogs to determine if hyperthermic alteration of tissue CDDP concentration is uniform. Eighteen female beagle dogs received 20, 50, or 80 mg/m2 CDDP by constant infusion for 60 min under normothermic or hyperthermic conditions (n = 3/subgroup). Blood, plasma, and ultrafiltered plasma samples were collected during the infusion. At termination of infusion, animals were immediately sacrificed, all major tissues were collected, and platinum levels were determined by atomic absorption spectroscopy. Platinum concentrations in all blood fractions of hyperthermic dogs tended to be lower than those of normothermic dogs. The correlation between dose and blood area under the concentration-time curve was linear at both temperatures. Each tissue concentration was normalized for that individual dog's blood area under the curve. The ratio of relative extraction at 42 degrees C to that at 37 degrees C were compared for each tissue. Values of 1.0 were interpreted as indicating uniform relative tissue extraction at each temperature. Values of greater than 2.0 were obtained in lung and ileum, while values of greater than 1.5 were obtained in liver, adrenal, stomach, colon, duodenum, spleen, and pancreas. Values of less than 1.0 were obtained in skin and superficial lymph nodes. These results indicate that hyperthermia significantly alters the pattern of CDDP tissue disposition in a nonuniform manner and that pharmacokinetic data obtained at one temperature, e.g., areas under the curve, cannot be used to directly predict tissue concentrations at another temperature.

Animals↗
PubMed1989

A case of urethral replacement with polytetrafluoro-ethylene graft for multiple anterior urethral strictures.

Recently, the authors had an opportunity to treat a 73-year-old male patient who was transferred to our institution with problematic multiple strictures of the anterior urethra subsequent to a suprapubic cystostomy. A proximal urethra was reconstructed with scrotal skin, but due to the shortage of distal skin, as a last resort we reconstructed a distal urethra using a polytetrafluoroethylene graft in place of 10 cm long urethral strictures. About 5 months after surgery, we had to reexplore the polytetrafluoroethylene graft area because of pain and found, much to our surprise, that the urethra had been completely regenerated around the length of polytetrafluoroethylene graft which now remained freely detached in the urethral canal. Following removal of the polytetrafluoroethylene graft, the patient could urinate normally and was subsequently discharged without further problems. We concluded that this case was incidentally successful with good regeneration of urethral mucosa of the anterior urethra by grafting a polytetrafluoroethylene tube.

Aged↗
PubMed1988

Modulation of cellular transglutaminase: protease-induced activation.

Multiple molecular forms of transglutaminase are found in cells and each form is widely distributed. We find a 95 K dalton enzyme associated with membrane fractions. A 50 K dalton enzyme occurs primarily in epidermis and hair follicles. Cells after treatment with proteases show greater transglutaminase activity. The activated enzyme in rat chondrosarcoma cells is one of 95 K daltons, whereas mouse epidermal cells and rabbit endometrium cells after protease activation display enzymes of both 95 K daltons and 50 K daltons. The 95 K dalton enzyme, but not that of 80 K daltons, can be activated by proteases or sulfhydryl compounds after cell lysis. In cells that undergo terminal differentiation, e.g., reticulocytes, megakaryocytes, monocytes, chondrocytes, and epidermal cells, the forms of transglutaminase are modulated. Our findings suggest that these modulations in differentiating cells are the results of transglutaminase post-translational modifications that cause pronounced changes in catalytic activity.

Animals↗
PubMed1986

Cellular transglutaminase. The particulate-associated transglutaminase from chondrosarcoma and liver: partial purification and characterization.

A transglutaminase from the malignant chondrocytes, rat swarm chondrosarcoma cells, was partially purified and characterized in an effort to understand transformation-induced changes in its activity. This enzyme separated by DE52 column chromatography after extraction from the particulate fraction of cell lysate was found to be distinct from previously characterized transglutaminases in its electrophoretic mobility, molecular size, substrate specificity, and immunologic reactivity. This enzyme was identified as a transglutaminase by its catalysis of amine (putrescine, spermine) incorporation at the carboxamide group of protein-bound gamma-glutamyl residues, and accordance of its kinetic data with the modified double displacement mechanism described for other transglutaminases. Limited proteolysis of the isolated enzyme resulted in a 3-4-fold increase of catalytic activity and a concomitant reduction of molecular size by approximately one-half. Incubation of labeled amine with chondrosarcoma cell lysate resulted in labeling of only a few proteins that appeared to be extensively cross-linked and that were located mostly in the particulate fraction of the cells. Transglutaminase extracted from the rat liver particulate fraction displayed enzymatic and structural properties closely resembling those of the enzyme from chondrosarcoma cells.

Alkylation↗
PubMed1985

Analysis of complete responders after initial treatment with chemotherapy in head and neck cancer.

We treated 60 patients with cisplatin-based combination chemotherapy before definitive surgery and/or radiation. All had squamous cell tumors of the head and neck, stages II to IV, M0. Twelve patients (20%) achieved a complete remission after chemotherapy. Eight of these patients showed no histologic evidence of residual disease after biopsy or surgery. Definitive local therapy with surgery and/or radiation was carried out on almost all patients regardless of the extent of the response to preceding chemotherapy. Chemotherapy-induced complete responders have had an improved survival rate in comparison with patients achieving a partial response or less. The extent of primary tumor correlates inversely with a complete response to chemotherapy.

Adult↗
PubMed1983

The adequacy of the Karnofsky Rating and Global Adjustment to Illness Scale as outcome measures in cancer rehabilitation and continuing care.

The Karnofsky Patient Performance Rating and the Global Adjustment to Illness Scale (Derogatis) were chosen to rate the physical status and psychosocial adjustment of 857 cancer patients participating in 6 Rehabilitation and Continuing Care (R/CC) programs. Both instruments are reported to have high interrater reliability, and administration is easy, fast, and non-intrusive to the patient. Repeated ratings were taken at hospital admission or initial assessment, discharge and at times of marked change to monitor patient status and to be used as outcome measures to evaluate the programs' impacts. The latter application has not been reported elsewhere. Changes in physical and psychosocial status from program entry to last contact were defined in terms of three outcomes: improvement, no change, deterioration. Adequacy of these ratings as outcome measures is evaluated in terms of generally accepted criteria for outcome measures and the operational experience during the program. The Karnofsky and GAIS instruments are judged favorably in terms of criteria for outcome measures in that they (1) relate to patient health status and the process of medical care; (2) are suitable for cancer patients; and (3) are not restricted to specific sites or complications. Three years' experience has resulted in the identification of difficulties in administration (appropriateness of specific descriptors of adjustment in particular situations or between ethnic or age groups, e.g. the GAIS is not appropriate for use among children) and interpretation of results (due to lack of norms for comparison). Overall, the scales are good measures of outcome. Adaptations of the scales based on their use with different age and ethnic groups might enhance the reliability and validity in this setting. Finally, norms need to be established if results are to be compared among different cancer patient populations.

Activities of Daily Living↗
PubMed1982

Myringoplasty (A review of 365 operations).

A series of 365 cases of tympanic membrane repair by the same surgeon is analysed, comparing the results of different techniques and grafting materials. A detailed study of 206 of these cases employing the underlay technique with temporal fascia is reported. In this group a graft take rate of 91.4 per cent in dry ears, and of 89.3 per cent in all cases, was achieved. Various factors liable to influence the success rate are analysed and discussed. No cases of conductive or sensori-neural hearing loss resulting from the operation were encountered.

Fascia↗
PubMed1981

Tympanoplasty.

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Ear Ossicles↗