• Tuberculosis and Respiratory Diseases
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• v.40 no.3
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• pp.236-249
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• 1993

Background: Among the injurious agents to which the lung airspaces are constantly exposed are reactive species of oxygen. It has been widely believed that reactive oxygen species may be implicated in the etiology of lung injuries. In order to elucidated how this oxidant causes lung cell injury, we investigated the effects of exogenous $H_2O_2$ on alveolar epithelial barrier characteristics. Methods: Rat type II alveolar epithelial cells were plated onto tissue culture-treated polycarbonate membrane filters. The resulting confluent monolayers on days 3 and 4 were mounted in a modified Ussing chamber and bathed on both sides with HEPES-buffered Ringer solution. The changes in short-circuit current (Isc) and monolayer resistance (R) in response to the exogenous hydroperoxide were measured. To determine the degree of cellular catalase participation in protection against $H_2O_2$ injury to the barrier, experiments were repeated in the presence of 20 mM aminotriazole (ATAZ, an inhibitor of catalase) in the same bathing fluid as the hydroperoxide. Results: These monolayers have a high transepithelial resistance (>2000 ohm-$cm^2$) and actively transport $Na^+$ from apical fluid. $H_2O_2$(0-100 mM) was then delivered to either apical or basolateral fluid. Resulting indicated that $H_2O_2$ decreased Isc and R gradually in dose-dependent manner. The effective concentration of apical $H_2O_2$ at which Isc (or R) was decreased by 50% at one hour ($ED_{50}$) was about 4 mM. However, basolateral $H_2O_2$ exposure led to $ED_{50}$ for Isc (and R) of about 0.04 mM. Inhibition of cellular catalase yielded $ED_{50}$ for Isc (and R) of about 0.4 mM when $H_2O_2$ was given apically, while $ED_{50}$ for basolateral exposure to $H_2O_2$ did not change in the presence of ATAZ. The rate of $H_2O_2$ consumption in apical and basolateral bathing fluids was the same, while cellualr catalase activity rose gradually with time in culture. Conclusion: Our data suggest that basolateral $H_2O_2$ may affect directly membrane component (e.g., $Na^+,\;K^+$-ATPase) located on the basolateral cell surface. Apical $H_2O_2$, on the other hand, may be largely degraded by catalase as it passes through the cells before reaching these membrane components. We conclude that alveolar epithelial barrier integrity as measured by Isc and R are compromised by $H_2O_2$ being relatively sensitive to basolateral (and insensitive to apical) $H_2O_2$.

• Radiation Oncology Journal
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• v.14 no.3
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• pp.221-228
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• 1996

Purpose : We tried to evaluate the clinical characteristics, the treatment methods, the results of treatments, and the Patterns of failure in ovarian dysgerminoma retrospectively According to the results we would like to suggest the proper management guideline of stage la ovarian dysgerminoma patients who want to maintain fertility. Materials and Methods : Between 1975 and 1990, 34 patients with ovarian dysgerminoma were treated at the Yonsei University Hospital. The case records of these patients have been reviewed for presenting symptoms, treatment methods, local control and survival following treatment. Excluded from analysis were five patients with mixed ovarian germ cell tumors and gonadoblastomas (46,XY) Treatment results of the twenty nine patients were analysed by each treatment modality. Twenty one patients were treated with surgery and postoperative adjuvant radiotherapy (group 2). The other eight patients were treated with operation alone (group 2). The median age of twenty-nine patients was 23 years with a range of 8 to 39 years. Presenting symptoms were abdominal mass (20) pelvic discomfort or pain (5) et al. Radiotherapy was performed by 10MV LINAC or Co-60 teletherapy unit. The total radiation dose of the whole abdomen was 20-25 Gy/3weeks, 1-1.5 Gy/fraction with a boost to the whole pelvis 10-15 Gy/l-2weeks 1.8-2.0 Gy/fraction. Advanced stage disease (stage II or stage III) patients received prophylactic mediastinal and supraclavicular irradiation to a dose of 16-26 Gy. Median duration of follow-up of living patients was 80 months (range 13-201 months). Results : All of the twenty one patients of group 1 were alive without disease ($100\%$). Among the eight patients who were not treated with radiotherapy (group 2), six patients developed local recurrence. Four Patients referred with recurrent disease were treated with salvage radiotherapy. Three of four patients were salvaged and one Patient who had recurrent intra-abdominal disease died of progressed carcinomatosis at 11 months after salvage radiotherapy. The other two patients with recurrence were salvaged with chemotherapy (1 patient) or re-operation (1 Patient). Twenty eight patients remained alive without disease at last follow up, so the 5 year local control rate and 5 year overall survival rate for all groups were $96.6\%$ (28/29), respectively. Among thirteen patients with stage la unilateral tumors seven patients were treated with postoperative radiotherapy and the other six patients were treated with unilateral salpingo-oophorectomy alone. Five patients who did not received radiotherapy developed local failure but all of the recurrent ovarian dysgerminomas were salvaged with radiotherapy, chemotherapy or re-operation. So all the 13 patients with stage la ovarian dysgerminoma were free of disease from 20-201 months (median 80 months). Conclusion : The authors consider external irradiation to be an effective treatment as a complement to surgery in ovarian dysgerminoma. For those patients with disease presenting in stage la tumors who wish to maintain fertility, unilateral salpingo-oophorectomy alone may be curative and spare ovarian function considering excellent salvage rate of recurrent ovarian dysgerminoma in present study.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.275-282
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• 1998

Purpose : The effect of hyperfractionated radiotherapy on locally advanced non-small lung cancer was studied by a retrospective analysis. Materials & Methods : We analyzed sixty one patients of biopsy-confirmed, IIIA and IIIB non-small cell lung cancer. Using the ECOG performance scale, all the patients were scored less than 2. They were treated by curative hyperfractionated radiotherapy alone from Oct. 1992 to Oct. 1995 at the Department of Radiation Oncology. All the patients received 120cGy b.i.d with more than 6 hours interval between each fraction. The total dose of radiation was reached up to 6400-7080 cGy with a mean dose of 6934 cGy. The results were analyzed retrospectively. Results : The overall survival rate was 53 1$\%$ in 1 year, 9.9$\%$ in 2 years with a median survival time (MST) of 13.9 months. The progression free survival (PFS) rate was 37.0$\%$ in 1 year, 8.9$\%$ in 2 years. Twenty two Patients were classified as complete responders to this treatment and their MST was 19.5 months When this was compared with that of partial responders (MST: 11 7months), it was statistically significant (p=0.0003). Twenty nine patients of stage IIIA showed a better overall survival rate (1yr 63.3$\%$, 2yr 16.8$\%$) than IIIB patients (1yr 43.3$\%$, 2yr 3.6$\%$), which was also statistically significant (p=0.003). Patients with adenocarcinoma showed a better survival rate (1yr 64.3$\%$, 2yr 21.4$\%$) than that of squamous cell counterpart (1yr 49.4$\%$, 2yr 7.4$\%$), although this was not significant statistically (p=0.61). Two patients developed fatal radiation-induced pneumonia right after the completion of the treatment which progressed rapidly and they all died within 2 months. One patient developed radiation-induced fibrosis after 13 months. He refused further treatment and died soon after the development of fibrosis. Conclusion : Among locally advanced NSCLC, hyperfractionated radiotherapy was effective on stage IIIA patients by increasing MST with acceptable toxicities. Acute radiation-induced pneumonia should be carefully monitored and must be avoided during or after this treatment.

• Journal of Ginseng Research
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• v.26 no.3
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• pp.111-131
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• 2002

Korean ginseng (Panax ginseng C.A. Meyer) received a great deal of attention from the Orient and West as a tonic agent, health food and/or alternative herbal therapeutic agent. However, controversy with respect to scientific evidence on pharmacological effects especially, evaluation of clinical efficacy and the methodological approach still remains to be solved. Author reviewed those articles published since 1980 when pharmacodynamic studies on ginseng have intensively started. Special concern was paid on metabolic disorders including diabetes mellitus, circulatory disorders, malignant tumor, sexual dysfunction, and physical and mental performance to give clear information to those who are interested in pharmacological study of ginseng and to promote its clinical use. With respect to chronic diseases such as diabetes mellitus, atherosclerosis, high blood pressure, malignant disorders, and sexual disorders, it seems that ginseng plays preventive and restorative role rather than therapeutics. Particularly, ginseng plays a significant role in ameliorating subjective symptoms and preventing quality of life from deteriorating by long term exposure of chemical therapeutic agents. Also it seems that the potency of ginseng is mild, therefore it could be more effective when used concomitantly with conventional therapy. Clinical studies on the tonic effect of ginseng on work performance demonstrated that physical and mental dysfunction induced by various stresses are improved by increasing adaptability of physical condition. However, the results obtained from clinical studies cannot be mentioned in the indication, which are variable upon the scientist who performed those studies. In this respect, standardized ginseng product and providing planning of the systematic clinical research in double-blind randomized controlled trials are needed to assess the real efficacy for proposing ginseng indication. Pharmacological mode of action of ginseng has not yet been fully elucidated. Pharmacodynamic and pharmacokinetic researches reveal that the role of ginseng not seem to be confined to a given single organ. It has been known that ginseng plays a beneficial role in such general organs as central nervous, endocrine, metabolic, immune systems, which means ginseng improves general physical and mental conditons. Such multivalent effect of ginseng can be attributed to the main active component of ginseng,ginsenosides or non-saponin compounds which are also recently suggested to be another active ingredients. As is generally the similar case with other herbal medicines, effects of ginseng cannot be attributed as a given single compound or group of components. Diversified ingredients play synergistic or antagonistic role each other and act in harmonized manner. A few cases of adverse effect in clinical uses are reported, however, it is not observed when standardized ginseng products are used and recommended dose was administered. Unfavorable interaction with other drugs has also been suggested, which the information on the products and administered dosage are not available. However, efficacy, safety, interaction or contraindication with other medicines has to be more intensively investigated in order to promote clinical application of ginseng. For example, daily recommended doses per day are not agreement as 1-2g in the West and 3-6 g in the Orient. Duration of administration also seems variable according to the purpose. Two to three months are generally recommended to feel the benefit but time- and dose-dependent effects of ginseng still need to be solved from now on. Furthermore, the effect of ginsenosides transformed by the intestinal microflora, and differential effect associated with ginsenosides content and its composition also should be clinically evaluated in the future. In conclusion, the more wide-spread use of ginseng as a herbal medicine or nutraceutical supplement warrants the more rigorous investigations to assess its effacy and safety. In addition, a careful quality control of ginseng preparations should be done to ensure an acceptable standardization of commercial products.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.407-416
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• 1996

The reactive intermediates formed during the metabolism of therapeutic agents, toxicants and carcinogens by cytochromes P450 are frequently capable of covalently binding to tissue macromolecules and causing tissue damage. It has been shown that YH439, a congener of malotilate, is effective in suppressing hepatic P450 2E1 expression. The present study was designed to further establish the mechanistic basis of YH439 protection against toxicant by assessing its effects against chemical-mediated potentiated hepatotoxicity. Retinoyl palmitate (Vit-A) pretreatment of rats for 7 days substantially enhanced carbon tetrachloride hepatotoxicity, as supported by an ${\sim}5-fold$ increase in serum alanine aminotransferase (ALT) activity, as compared to $CCl_4$ treatment alone. The elevation of ALT activity due to Vit-A was completely blocked by the treatment of $GdCl_3$ a selective inhibitor of Kupffer cell activity. Concomitant pretreatment of rats with both YH439 and Vit-A resulted in a 94% decrease in Vit-A-potentiated $CCl_4$ hepatotoxicity. YH439 was also effective against propyl sulfide-potentiated $CCl_4-induced$ hepatotoxicity. Whereas propyl sulfide (50 mg/kg, 7d) enhanced $CCl_4-induced$ hepatotoxicity by >5-fold, relative to $CCl_4$ treatment alone, concomitant treatment of animals with both propyl sulfide and YH439 at the doses of 100 and 200 mg/kg prevented propyl sulfide-potentiated $CCl_4$ hepatotoxicity by 35% and 90%, respectively. Allyl sulfide, a suppressant of hepatic P450 2E1 expression, completely blocked the propyl sulfide-enhanced hepatotoxicity, indicating that propyl sulfide potentiation of $CCl_4$ hepatotoxicity was highly associated with the expression of P450 2E1 and that YH439 blocked the propyl sulfide-enhanced hepatotoxicity through modulation of P450 2E1 levels. Propyl sulfide- and $CCl_4-induced$ stimulation of lipid peroxidation was also suppressed by YH439 in a dose-related manner, as supported by decreases in malonedialdehyde production. The role of P450 2E1 induction in the potentiation of $CCl_4$ toxicity and the effects of YH439 were further evaluated using pyridine as a P450 2E1 inducer. Pyridine pretreatment substantially enhanced the $CCl_4$ hepatotoicity by 23-fold, relative to $CCl_4$ alone. YH439, however, failed to reduce the pyridine-potentiated toxicity, suggesting that the other form(s) of cytochroms P450 inducible by pyridine, but not suppressible by YH439 treatment, may play a role in potentiating $CCl_4-induced$ hepatotoxicity. YH439 was capable of blocking cadmium chloride-induced liver toxicity in mice. These results demonstrated that YH439 efficiently blocks Vit-A-enhanced hepatotoxiciy through Kupffer cell inactivation and that the suppression of P450 2E1 expression by YH439 is highly associated with blocking of propyl sulfide-mediated hepatotoxicity.

• Radiation Oncology Journal
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• v.20 no.3
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• pp.221-227
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• 2002

Purpose : To evaluate the role of postoperative chemoradiotherapy in locally advanced rectal cancer, we retrospectively analyzed the treatment results of patients treated by curative surgical resection and postoperative chemoradiotherapy. Materials and Methods : From April 1989 through December 1998, 119 patients were treated with curative surgery and postoperative chemoradiotherapy for rectal carcinoma in Gyeongsang National University Hospital. Patient age ranged from 32 to 73 years, with a median age of 56 years. Low anterior resection was peformed in 59 patients, and abdominoperineal resection in 60. Forty-three patients were AJCC stage II and 76 were stage III. Radiation was delivered with 6 MV X rays using either AP-PA two fields, AP-PA both lateral four fields, or PA both lateral three fields. Total radiation dose ranged from 40 Gy to 56 Gy. In 73 patients, bolus infusions of 5-FU $(400\;mg/m^2)$ were given during the first and fourth weeks of radiotherapy. After completion of radiotherapy, an additional four to six cycles of 5-FU were given. Oral 5-FU (Furtulone) was given for nine months in 46 patients. Results : Forty $(33.7\%)$ of the 119 patients showed treatment failure. Local failure occurred in 16 $(13.5\%)$ patients, 1 $(2.3\%)$ of 43 stage II patients and 15 $(19.7\%)$ of 76 stage III patients. Distant failure occurred in 31 $(26.1\%)$ patients, among whom 5 $(11.6\%)$ were stage II and 26 $(34.2\%)$ were stage III. Five-year actuarial survival was $56.2\%$ overall, $71.1\%$ in stage II patients and $49.1\%$ in stage III patients (p=0.0008). Five-year disease free survival was $53.3\%$ overall, $68.1\%$ in stage II and $45.8\%$ in stage III (p=0.0006). Multivariate analysis showed that T stage and N stage were significant prognostic factors for five year survival, and that T stage, N stage, and preoperative CEA value were significant prognostic factors for five year disease free survival. Bowel complication occurred in 22 patients, and was treated surgically in 15 $(12.6\%)$, and conservatively in 7 $(5.9\%)$. Conclusion : Postoperative chemoradiotherapy was confirmed to be an effective modality for local control of rectal cancer, but the distant failure rate remained high. More effective modalities should be investigated to lower the distant failure rate.

• Journal of Ginseng Research
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• v.27 no.3
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• pp.103-109
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• 2003

We investigated the effect of ginseng total saponin (GTS) on the regeneration process of experimentally crush injured rat sciatic nerves. The bilateral sciatic nerves of fifty adult male Sprague-Dawley rats were compressed surgically with a straight hemostat for 30 seconds with 1 mm width. Twenty rats were divided into four groups to test the dose-dependent effect of GTS (0, 50, 100, or 150 mg/kg, i.p.). Saline for vehicle control group or GTS dissolved in saline was administerd for three weeks. After that period of time, the numbers of total myelinated axon and degenerated myelin in the sciatic nerves of bilateral legs were examined and analyzed using image analysis system to confirm a morphological effect of GTS. We found that the most effective concentration of GTS for the regeneration of damaged sciatic nerve was 150 mg/kg. In another set of experiment, thirty rats were divided into two groups as saline-treated vehicle group and GTS-treated group (150 mg/kg, i.p.) for three weeks. Every week we examined the numbers of total myelinated axon and degenerated myelin in the sciatic nerves of bilateral legs using image analysis system to evaluate the effect of GTS on injured nerves. We found that the regeneration of damaged sciatic nerves was facilitated in GTS-treated group compared to saline-treated group until two weeks. However, after that period of time we could not observe the significant difference between saline-treated group and GTS-treated group. These results suggest that GTS is a useful adjuvant therapy for the regeneration of the peripheral nerve injury in short period of treatment.

• Journal of Food Hygiene and Safety
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• v.28 no.1
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• pp.31-35
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• 2013

In this study, the pesticide residues of polished rice and brown rice were measured after washing and cooking process. The initial concentrations of isoprothiolane and fthalide were $7.134{\pm}0.03mg/kg$ and $2.024{\pm}0.04mg/kg$ for polished rice, and $17.941{\pm}1.41mg/kg$ and $6.413{\pm}0.19mg/kg$ for brown rice, respectively. After first washing process, the removal rates of isoprothiolane were 23.0% (polished rice) and 18.5% (brown rice). Also, the case of fthalide, the removal rates were 14.0% and 9.7%, respectively. The removal dose was increased, but the removal rate was decreased in proportion to the number of washing process, After the cooking process, the removal rates of isoprothiolane and fthalide were 66.0% and 79.0% (polished rice), and 88.7% and 92.9% (brown rice), respectively. The removal rate of isoprothiolane was higher in the washing process, and the case of fthalide was higher in the cooking process. The optimum washing process for the pesticides removal was five times and the cooking process was the most effective to use the new water after soaking the rice in water during 30 minutes.

• Tuberculosis and Respiratory Diseases
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• v.56 no.6
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• pp.611-618
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• 2004

Background : Idiopathic pulmonary fibrosis(IPF), a subtype of IIP(idiopathic interstitial pneumonia), is a fatal disease with a 3-5 year median survival. Many attempts at treating this condition have failed to demonstrate a survival benefit in IPF. Recently Ziesche et $al^{12}$ reported the efficacy of IFN-${\gamma}$ for treating IPF but there is still some controversy. The aim of this study was to determine the efficacy of IFN-${\gamma}$ in patients with advanced IPF who had not been responsive to steroid and cytotoxic agents. Method : Nine patients with advanced IPF(age: $55.4{\pm}15.3$ years, Male: Female=8:1) were enrolled. One year treatment regime with 2 million IU of IFN-${\gamma}$ administered subcutaneously three times a week, and low dose prednisolone(10-30 mg/d) was also used. In the case of a definite aggravation and serious side effects, the IFN-${\gamma}$ was discontinued. During the IFN-${\gamma}$ trial, a pulmonary function test and chest radiography were checked every three month throughout the study. Result : 1) Among 9 patients, only 4 patients were able to complete the 12 month treatment with IFN-${\gamma}$, and 5 patients died during the treatment period. 2) No improvement either in the respiratory symptoms or pulmonary functions were observed any of the patients, even in those who completed the 12 months trial of IFN-${\gamma}$, 3) At the time of IFN-${\gamma}$ trial, the survivors who finished the IFN-${\gamma}$ treatment for 12 months had a higher oxygen level($81.3{\pm}2.8$ vs. $67.4{\pm}8.4$, P=0.024) and a better pulmonary function(FVC: $61.3{\pm}5.1$ % predicted vs. $45.7{\pm}12.3%$, P=0.048, and $D_Lco$: $45.0{\pm}5.0%$ predicted vs. $30.8{\pm}11.2%$, P=0.048) than the non-survivors. Conclusion : Our data suggested that IFN-${\gamma}$ therapy was not effective in the patients with advanced IPF refractory compared with other therapeutic agents. Furthermore, these results suggest that severe impairment of the pulmonary function and hypoxemia during the IFN-${\gamma}$ therapy requires special attention.

• Tuberculosis and Respiratory Diseases
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• v.64 no.1
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• pp.8-14
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• 2008

Background: Acinetobacter infections are difficult to treat as they often exhibit multiple resistance to the antibiotics that are currently available for the treatment of pneumonia. Colistin is active against gram-negative bacteria, including the multiple drug resistant (MDR) Acinetobacter species. However, intravenous administration of colistin was abandoned because of its nephrotoxicity and neurotoxicity. The aims of this study were to examine the efficacy and safety of colistin administered by aerosol in the treatment of pneumonia caused by MDR Acinetobacter baumannii. Methods: We retrospectively reviewed the medical records of patients admitted to the intensive care unit (ICU) from Dec. 2006 to Aug. 2007 who had been diagnosed as suffering from pneumonia due to MDR Acinetobacter baumannii and had been treated with nebulized colistin. Results: 31 patients received aerosolized colistin. The average duration of the treatment was $14{\pm}7$ days and the daily dose of ranged from 225 mg to 300 mg. All patients received concomitant intravenous antimicrobial agents. The average length of the stay in the ICU was $34{\pm}21$ days and in the hospital $58{\pm}52$ days. The overall microbiological eradication was observed in 25 patients (80.6%). 14 of these (56%) were cured, and 11 (44%) were infected with other microorganisms. The overall crude mortality of the ICU was 48%. Nephrotoxicity and significant bronchial constriction did not occur in any patient during neublized colistin treatment. Conclusion: Nebulized colistin may be a safe and effective option in the treatment of pneumonia due to MDR Acinetobacter baumannii. Its role in therapy warrants further investigation in comparative studies.