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Biomedical subjects

C C Chan

Publications and source records attributed to C C Chan.

At least 235 records · Page 13Linked to original sources

Respiratory and irritant health effects of a population living in a petrochemical-polluted area in Taiwan.

Reported herewith are the results from an ongoing study of outdoor air pollution and the health of persons living in the communities in close proximity to petrochemical industrial complexes. To determine if there is an excess of adverse health outcomes in the population exposed to petrochemical industrial emissions, a health survey was undertaken in 1996 in this area and in one reference area which has no local industrial emissions. The subjects were 436 adults (30-64 years of age) living in the Sanwei area (exposed area) and 488 in Taicei (reference area). For several indicators of respiratory health, including cough, wheezing, and chronic bronchitis, the prevalence rates were not significantly different between the study and the control populations. Acute irritative symptoms (eye irritation, nausea, throat irritation, and chemical odor perception) were significantly more common in the exposed area, particularly perception of chemical odors (84.6% vs 2.1%). It is concluded that exposure to petrochemical air emissions may be associated with increased rates of acute irritative symptoms. Future studies are needed to identify the potential role of petrochemical industrial emissions (particularly volatile organic compounds) in the genesis of acute irritative symptoms in a nearby petrochemical industrial area.

Adult↗

Effect of gallium nitrate on experimental autoimmune uveitis.

Gallium nitrate (GN) has been shown to inhibit T cell-mediated inflammatory disease. The purpose of our study was to test the effect of gallium nitrate (GN) on experimental autoimmune uveitis (EAU). Experimental autoimmune uveitis was induced in male Lewis rats immunized with retinal S-antigen. Rats received subcutaneous injections of GN or saline one day prior to immunization and 1, 4, 7, 10, 13, 16, and 19 days after immunization. Ocular inflammation was graded clinically and histologically by masked observers, and in vitro assays of cell-mediated and humoral immunity were performed. GN significantly inhibited the development of EAU graded clinically (P = 0.001) and histologically (P = 0.002). Treatment with GN also resulted in a small (30-41%) decrease in the lymphocyte responses to retinal S-Antigen and a small (12-37%) reduction in antibody production to S-antigen. These data show that GN suppresses the development of EAU, and inhibits both lymphocyte proliferative responses to antigen and antibody production.

Animals↗

Pathophysiological mechanism of seasonal affective disorder.

Despite the long history in medicine, the pathophysiological mechanism(s) of seasonal affective disorder (SAD) remain largely unknown. By employing a meta-analytic methodology, the authors of this study attempted to verify the validity of different pathophysiological mechanism(s) proposed for SAD. The findings showed that for phototherapy of medium light intensity, a combination of morning-evening therapy regime yielded the best therapeutic effect, and the antidepressant effect of the morning-evening light regime was superior to a single pulse of light administered at other times of day. Furthermore, the data showed that the antidepressant effect of a single pulse of light was similar for morning, midday, and evening light. These findings supported the photon-count hypothesis and refuted the proposed photoperiod, melatonin, and phase-shifting models of SAD.

Circadian Rhythm↗

Evaluation of external dose equivalent with thermoluminescent dosimeters from residents living in radiation-contaminated buildings.

As of October 1996 there are more than 90 radiation-contaminated steel supported rebar buildings (containing more than 1000 apartments) dispersed in the northern part of Taiwan. These apartments were contaminated with cobalt-60 at a total activity ranging from 1-140 microSv/yr. In this paper, a method is developed for evaluating external dose equivalent and dose equivalent rates encountered by the residents wearing specially designed thermoluminescent dosimeter (TLD)-embedded chains, belts and badges. Comparisons are also made between the TLD readings and the exposure readings from indoor layout personal dosimetry surveys and room occupancy adjustments to the buildings. The accuracy and sensitivity of the TLDs compared with the ionization chamber readings are judged to be considerable improvements over those of previous studies. From the present study, it is concluded that the reliability of the daily activity records provided by the residents during the entire TLD-wearing period is the most critical but challenging feature of the external dose equivalent measurement.

Activities of Daily Living↗

T cell mechanisms in experimental autoimmune uveoretinitis: susceptibility is a function of the cytokine response profile.

This study addresses the question whether susceptibility versus resistance to experimental autoimmune uveoretinitis (EAU) is connected to a Th1-type (interferon-gamma high, interleukin-4 low), versus a Th2-type (IFN-gamma low, IL-4 high) response. Primed lymph node cells of susceptible Lewis rats produced IFN-gamma in response to antigen in culture and transferred EAU to syngeneic recipients, whereas lymph node cells of resistant F344 rats made no IFN-gamma and did not transfer disease. Reversal of the disease pattern, by treatment of F344 rats with B. pertussis toxin and immunisation of Lewis rats with antigen in incomplete Freund's adjuvant, resulted in a parallel reversal of these response patterns. Neither strain produced significant IL-4 responses. A study of the response patterns in mice confirmed that high Th1 responders were susceptible, whereas low Th1 responders and Th2 responders were resistant. We conclude that susceptibility to EAU is connected with a Th1-dominant response, but resistance can involve either a 'null', F344-like response (Th1-low/Th2-low) or a Th2-dominant response.

Adoptive Transfer↗

Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor.

1. DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furan one) was identified as a novel orally active and highly selective cyclo-oxygenase-2 (COX-2) inhibitor. 2. In CHO cells stably transfected with human COX isozymes, DFU inhibited the arachidonic acid-dependent production of prostaglandin E2 (PGE2) with at least a 1,000 fold selectivity for COX-2 (IC50 = 41 +/- 14 nM) over COX-1 (IC50 > 50 microM). Indomethacin was a potent inhibitor of both COX-1 (IC50 = 18 +/- 3 nM) and COX-2 (IC50 = 26 +/- 6 nM) under the same assay conditions. The large increase in selectivity of DFU over indomethacin was also observed in COX-1 mediated production of thromboxane B2 (TXB2) by Ca2+ ionophore-challenged human platelets (IC50 > 50 microM and 4.1 +/- 1.7 nM, respectively). 3. DFU caused a time-dependent inhibition of purified recombinant human COX-2 with a Ki, value of 140 +/- 68 microM for the initial reversible binding to enzyme and a kappa 2 value of 0.11 +/- 0.06 s-1 for the first order rate constant for formation of a tightly bound enzyme-inhibitor complex. Comparable values of 62 +/- 26 microM and 0.06 +/- 0.01 s-1, respectively, were obtained for indomethacin. The enzyme-inhibitor complex was found to have a 1:1 stoichiometry and to dissociate only very slowly (t1/2 = 1-3 h) with recovery of intact inhibitor and active enzyme. The time-dependent inhibition by DFU was decreased by co-incubation with arachidonic acid under non-turnover conditions, consistent with reversible competitive inhibition at the COX active site. 4. Inhibition of purified recombinant human COX-1 by DFU was very weak and observed only at low concentrations of substrate (IC50 = 63 +/- 5 microM at 0.1 microM arachidonic acid). In contrast to COX-2, inhibition was time-independent and rapidly reversible. These data are consistent with a reversible competitive inhibition of COX-1. 5. DFU inhibited lipopolysaccharide (LPS)-induced PGE2 production (COX-2) in a human whole blood assay with a potency (IC50 = 0.28 +/- 0.04 microM) similar to indomethacin (IC50 = 0.68 +/- 0.17 microM). In contrast, DFU was at least 500 times less potent (IC50 > 97 microM) than indomethacin at inhibiting coagulation-induced TXB2 production (COX-1) (IC50 = 0.19 +/- 0.02 microM). 6. In a sensitive assay with U937 cell microsomes at a low arachidonic acid concentration (0.1 microM), DFU inhibited COX-1 with an IC50 value of 13 +/- 2 microM as compared to 20 +/- 1 nM for indomethacin. CGP 28238, etodolac and SC-58125 were about 10 times more potent inhibitors of COX-1 than DFU. The order of potency of various inhibitors was diclofenac > indomethacin approximately naproxen > nimesulide approximately meloxicam approximately piroxicam > NS-398 approximately SC-57666 > SC-58125 > CGP 28238 approximately etodolac > L-745,337 > DFU. 7. DFU inhibited dose-dependently both the carrageenan-induced rat paw oedema (ED50 of 1.1 mg kg-1 vs 2.0 mg kg-1 for indomethacin) and hyperalgesia (ED50 of 0.95 mg kg-1 vs 1.5 mg kg-1 for indomethacin). The compound was also effective at reversing LPS-induced pyrexia in rats (ED50 = 0.76 mg kg-1 vs 1.1 mg kg-1 for indomethacin). 8. In a sensitive model in which 51Cr faecal excretion was used to assess the integrity of the gastrointestinal tract in rats, no significant effect was detected after oral administration of DFU (100 mg kg-1, b.i.d.) for 5 days, whereas chromium leakage was observed with lower doses of diclofenac (3 mg kg-1), meloxicam (3 mg kg-1) or etodolac (10-30 mg kg-1). A 5 day administration of DFU in squirrel monkeys (100 mg kg-1) did not affect chromium leakage in contrast to diclofenac (1 mg kg-1) or naproxen (5 mg kg-1). 9. The results indicate that COX-1 inhibitory effects can be detected for all selective COX-2 inhibitors tested by use of a sensitive assay at low substrate concentration. The novel inhibitor DFU shows the lowest inhibitory potency against COX-1, a consistent high selectivity of inhibition of COX-2 over COX-1 (>300 fold) with enzyme, whole cell and whole blood assays, with no detectable loss of integrity of the gastrointestinal tract at doses >200 fold higher than efficacious doses in models of inflammation, pyresis and hyperalgesia. These results provide further evidence that prostanoids derived from COX-1 activity are not important in acute inflammatory responses and that a high therapeutic index of anti-inflammatory effect to gastropathy can be achieved with a selective COX-2 inhibitor.

Administration, Oral↗

Hyperdynamic circulation of cirrhotic rats with ascites: role of endotoxin, tumour necrosis factor-alpha and nitric oxide.

1. Hyperdynamic circulation observed in portal hypertensive states is characterized by generalized vasodilation, increased cardiac index and increased systemic and regional blood flows. Endotoxin, tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) have been reported to be involved in the pathogenesis of hyperdynamic circulation, but the interactions between endotoxin, TNF-alpha and NO in cirrhotic rats with ascites have never been specifically addressed. 2. This study was designed to determine systemic and portal haemodynamics and plasma levels of endotoxin, TNF-alpha and nitrate/nitrite in cirrhotic rats with ascites and investigate the relationships between these substances. 3. Plasma concentrations of endotoxin, TNF-alpha and nitrate/nitrite (an index of NO production) were determined in 25 cirrhotic rats with ascites and 17 control rats using the Limulus assay, ELISA and a colorimetric assay respectively. In addition, haemodynamic studies were performed in another ten cirrhotic rats with ascites and ten control rats. 4. Cirrhotic rats with ascites had hyperdynamic circulation accompanied by increased plasma levels of endotoxin, TNF-alpha and nitrate/nitrite, as compared with control rats. Significant correlation existed between plasma levels of endotoxin and nitrate/ nitrite (r = 0.59, P < 0.0001) and between plasma levels of endotoxin and TNF-alpha (r = 0.63, P < 0.0001). No correlation was detected between plasma levels of TNF-alpha and nitrate/nitrite (r = 0.24, P > 0.05). 5. This study suggests that endotoxaemia developed in cirrhotic rats with ascites may stimulate NO formation directly or indirectly via cytokine cascade, and consequently participate in the development and/or maintenance of hyperdynamic circulation.

Animals↗

Oral tolerance in a murine model of relapsing experimental autoimmune uveoretinitis (EAU): induction of protective tolerance in primed animals.

Oral administration of uveitogenic retinal antigens suppresses the expression of EAU induced by a subsequent immunization with these antigens. Effectiveness and mechanisms of oral tolerance in EAU have mainly been studied in the acute, monophasic model in Lewis rats by feeding antigen prior to induction of disease. In this study we investigated the effect of oral tolerance induction in the acute as well as the chronic-relapsing models in the B10.A mouse. In acute murine EAU we could effectively suppress disease by induction of oral tolerance prior to immunization. In the chronic-relapsing EAU, antigen feeding was started only after the animals had recovered from their first attack of uveitis. Under these experimental conditions the subsequent relapse was largely prevented. These experiments demonstrate that oral tolerance may have practical clinical implications in uveitis, which is predominantly a chronic-relapsing condition in humans.

Acute Disease↗

60Co contamination in recycled steel resulting in elevated civilian radiation doses: causes and challenges.

Since late 1992, more than 100 building complexes containing public and private schools and nearly 1,000 apartments have been identified in Taiwan with elevated levels of gamma-radiation from construction steel contaminated with 60Co. Due to improper handling of 60Co contaminated scrap steel in late 1982 and 1983, contaminated construction materials have been widely distributed throughout the country. These contaminated construction materials have generated elevated radiation exposures to members of the public in Taiwan. As of early 1996, more than 4,000 people, including young students, have been identified as receiving more than 1 mSv y(-1) above the local background for up to 12 y. This report provides a detailed discussion of the sources of the 60Co contamination in construction steel, its discovery in the building complexes, and preliminary evaluation and remediation activities.

California↗

Spectral properties of phototherapy for seasonal affective disorder: a meta-analysis.

The general therapeutic effect of light on seasonal affective disorder (SAD) has been widely acknowledged. However, the antidepressant effect of light does not seem to be the same for different spectra of light. In this study, the authors attempted to study the spectral properties of phototherapy for SAD using a meta-analytical procedure. The findings suggested that light of short to medium wavelengths (blue/green/yellow) seem to be essential for the therapeutic effect of light on SAD. Red wavelengths were relatively ineffective. It was then postulated that SAD may be predisposed and/or precipitated by the inefficiency of the S and M cones in the retina. Furthermore, ultraviolet (UV) waves did not seem to be essential for SAD symptom alleviation by artificial light. Therefore, these potentially harmful UV waves should be blocked in any clinical application of phototherapy for SAD.

Analysis of Variance↗

Maximal respiratory pressures in adult Chinese, Malays and Indians.

Maximal static inspiratory and expiratory mouth pressures (PI,max and PE,max, respectively) enable the noninvasive measurement of global respiratory muscle strength. The aim of this study was primarily to obtain normal values of PI,max and PE,max for adult Chinese, Malays and Indians and, secondarily, to study their effect on lung volumes in these subjects. Four hundred and fifty two healthy subjects (221 Chinese, 111 Malays, 120 Indians) were recruited. Measurements of PI,max from residual volume (RV), PE,max from total lung capacity (TLC) and forced vital capacity (FVC) were obtained in the seated position. There were significant ethnic differences in PI,max and PE,max measurements obtained in males, and FVC measurements in both males and females. Chinese males had higher PI,max values (mean (+/-SD) 88.7+/-32.5 cmH2O) and higher PE,max values (113.4+/-41.5) than Malay males (PI,max 74.0+/-22.7 cmH2O, PE,max 94.7+/-23.4 cmH2O). Chinese males had higher PE,max than Indian males (PI,max = 83.7+/-30.0 cmH2O, PE,max 98.4+/-29.2 cmH2O). There were no significant differences among Chinese females (PI,max 53.6+/-2.3 cmH2O, PE,max 68.3+/-24.0 cmH2O), Malay females (PI,max 50.7+/-18.3 cmH2O, PE,max 63.6+/-21.6 cmH2O) and Indian females (PI,max 50.0+/-15.2 cmH2O, PE,max 60.7+/-20.4 cmH2O). In both sexes, the Chinese had a higher FVC compared with Malays and Indians. After adjusting for age, height and weight, race was still a determinant for PE,max in males, and FVC in both sexes. The FVC only correlated weakly with PI,max and PE,max in both sexes. Ethnic differences in respiratory muscle strength, and lung volumes, occur among Asians. However, respiratory muscle strength does not explain the differences in lung volumes in healthy Asian subjects.

Adult↗

Comparison of two oral evacuants (Citromag and Golytely) for bowel preparation before barium enema.

Oral regimens for bowel preparation before barium enema examination are routinely used because of their convenience and simplicity, rather than the traditional method of colonic wash-out. We performed a prospective study comparing the side-effects and efficacy of two commonly used oral bowel evacuants (Citromag and Golytely) for bowel preparation before barium enema examination in 102 patients. The side-effects associated with the agents were assessed by analysing a questionnaire completed by the patients. There was no significant difference in the side-effects between the two agents although more patients taking Golytely (45.5%) deemed its taste unacceptable than those taking Citromag (25.9%). The results of the bowel preparation were assessed by two independent radiologists giving scores on the amount of faecal residue and the quality of mucosal coating. The amount of faecal residue was less in the Golytely group (p < 0.05). The quality of mucosal coating by barium was also better in the Golytely group than the Citromag group (p < 0.05).

Adolescent↗

Prognostic value of plasma endotoxin levels in patients with cirrhosis.

BACKGROUND: Endotoxemia has frequently been observed in patients with cirrhosis. Previous studies have shown that cirrhotic patients with endotoxemia have a higher mortality than those without. We evaluated the clinical value of plasma endotoxin level in predicting short-term (3 months) and long-term (2 years) survival among cirrhotic patients and compared it with the Child-Pugh score. METHODS: Plasma endotoxin levels were determined in 102 cirrhotic patients without clinical evidence of infection by a quantitative Limulus assay. The patients were followed up for 3 months to assess short-term survival and for 2 years for long-term survival. RESULTS: Plasma endotoxin levels increased progressively as liver function deteriorated. In short-term survival analysis, plasma endotoxin levels were significantly higher in non-survivors than those in survivors (10.6 +/- 2.2 pg/ml versus 5.8 +/- 0.5 pg/ml; P < 0.05). Both plasma endotoxin and serum bilirubin levels, but not the Child-Pugh score, were significant factors in predicting short-term survival in multivariate analysis. In long-term survival analysis, plasma endotoxin levels did not differ significantly between survivors and non-survivors (6.1 +/- 0.6 pg/ml versus 7.3 +/- 1.1 pg/ml; P > 0.05) and was not an independent predictor of long-term survival. In contrast, both Child-Pugh score and serum bilirubin levels were significant predictors of long-term survival in multivariate analysis. CONCLUSIONS: In patients with cirrhosis, plasma endotoxin levels progressively increase as liver function deteriorates and may be useful in predicting short-term survival.

Aged↗

Effect of transforming growth factor beta-1 in endotoxin-induced uveitis.

PURPOSE: Transforming growth factor beta-1 (TGF beta-1) can modulate inflammation. Endotoxin-induced uveitis (EIU) is characterized by acute ocular inflammation related to the release of cytokines, including interleukin (IL)-6. The authors investigated the effect of TGF beta-1 on EIU in mice. METHODS: Three independent experiments were performed. Endotoxin-induced uveitis was induced in C3H/HeN mice by an injection of 200 micrograms of lipopolysaccharide (LPS). Two micrograms of TGF beta-1 in 0.1 ml phosphate-buffered saline (PBS) or 0.1 ml PBS alone was administered intraperitoneally at 8 hours after LPS injection. Twenty-four hours after LPS injection, the aqueous humor of the right eyes was collected for leukocyte count, protein concentration, and IL-6 assay. Left eyes were processed for routine histology. RESULTS: TGF beta-1-treated mice showed less ocular inflammation histologically than to the animals that were given PBS. This was confirmed by decreases in leukocyte count, protein concentration, and IL-6 level in the aqueous humor. CONCLUSIONS: TGF beta-1 inhibits the development of EIU. TGF beta-1 may be useful for the modulation of uveitis in humans.

Animals↗

Upregulation of vascular endothelial growth factor in ischemic and non-ischemic human and experimental retinal disease.

Vascular endothelial growth factor (VEGF) is induced by hypoxia and it has been implicated in the development of iris and retinal neovascularization (NV) in ischemic retinopathies in which it has been suggested that Muller cells are responsible for increased VEGF production. VEGF, however, is also known to be a potent mediator of vascular permeability in other tissues and may perform this function in retina. Immunohistochemical staining for VEGF was performed on a variety of human and experimental ischemic and non-ischemic ocular disorders in which blood retinal barrier (BRB) breakdown is known to occur to determine if there is an upregulation of VEGF in these conditions. We found increased VEGF immunoreactivity in ganglion cells of rats with oxygen-induced ischemic retinopathy and in ganglion cells, the inner plexiform layer, and some cells in the inner nuclear layer of rats with experimental autoimmune uveoretinitis (EAU), in which there was no identifiable ischemia or NV. In rats with EAU, VEGF staining intensity increased from 8 to 11 days after immunization, coincident with BRB failure. These results were confirmed using two distinct anti-VEGF antibodies and by immunoblot and the immunohistochemical staining was eliminated by pre-incubating the antibodies with VEGF peptide. VEGF staining was also increased in the retina and iris of patients with ischemic retinopathies, such as diabetic retinopathy and retinal vascular occlusive disease, and in patients with disorders in which retinal ischemia does not play a major role, such as aphakic/ pseudophakic cystoid macular edema, retinoblastoma, ocular inflammatory disease or infection, and choroidal melanoma. VEGF was primarily localized within retinal neurons and retinal pigmented epithelial cells in these cases. In addition or in association with its role of inducing NV, VEGF may contribute to BRB breakdown in a variety of ocular disorders and blockage of VEGF signaling may help to reduce some types of macular edema.

Animals↗

Use of topical FK506 in a corneal graft rejection model in Lewis rats.

PURPOSE: To evaluate the immunosuppressive effect of topical FK506 on allograft corneal rejection in rats. METHODS: Lewis rats were used as recipients and Fisher rats as corneal graft donors. In Experiment 1, all rats received intraperitoneally FK506 (0.3 mg/kg per day) for 7 days to ensure equal baseline parameters. The rats then were assigned randomly to treatment with topical 0.3% FK506 or vehicle alone. In another set of experiments, rats were treated only with topical treatment. The grafts were inspected by clinical evaluation. Corneas obtained at the time of maximum rejection were used for histology and immunohistochemistry. RESULTS: The selected combination of rat strains caused 100% graft rejection in untreated animals within 2 weeks after the penetrating keratoplasty. In the treated animals, rejection was delayed until the end of topical therapy. One third of corneal grafts remained clear until day 30. Histologic and immunohistochemical studies confirmed the clinical evaluations. Untreated rat corneas had a large number of infiltrating helper-inducer T cells, macrophages, interleukin-2 receptor-expressing cells, and Ia-antigen-expressing cells. At the same timepoint, topically treated corneas showed a limited inflammatory response characterized by a 2/3 reduction in the number of infiltrating helper and cytotoxic cells, and a five-fold decrease in the expression of class I and class II major histocompatibility antigens. CONCLUSIONS: Topical FK506 treatment is an effective way of preventing corneal graft rejection in the Lewis rat corneal graft model. It shows promise as a drug to prevent corneal graft rejection in humans.

Administration, Topical↗