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A Study of Working Environments and Workers Exposed to Chromium (크롬 취급 사업장의 작업환경 및 근로자 폭로 실태에 관한 연구)

  • Yu, Byung-Chul;Son, Byung-Chul;Jun, Jin-Ho;Han, Yong-Soo;Son, Hye-Sook;Lee, Chae-Eun;Jeong, Woon
    • Journal of Preventive Medicine and Public Health
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    • v.27 no.3 s.47
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    • pp.517-530
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    • 1994
  • For the purpose of providing the basic data for health management of workers who are exposed to chromium and for improving the quality of working environment, the authors evaluated blood and urinary level of chromium, the occupational history. AST, ALT, Hb, Hct, nasal specular examinaton on 287 workers who have been dealed chromium compounds in 56 manufacturing Industries of five types, that is, 38 metal plating services(plating),4 manufacture of other fabricated metal products (fabricated metal product), 5 manufacturing of dyestuff(dyestuff), 6 dressing and dyeing of leather(leather), 3 others(manufacture of pottery and ceramic househod wares, motor vehicles, electronic valves and tubes and other electronic components) and also measured the level of chromium in air from February to October 1993. The results were as follows ; 1. The utilized type of chromium compounds was the hexavalent state in plating fabricated metal product dyestuff, leather and the trivalent state in .other, and atmosperic chromium concentration as geometric mean was $0.0138mg/m^3(0.001{\sim}0.068mg/m^3)$ in plating, $0.0115mg/m^3(0.006{\sim}0.015mg/m^3)$ in fabricated matal product, $0.068mg/m^3(0.002{\sim}0.019mg/m^3)$ in dyestuff, $0.0083mg/m^3(0.002{\sim}0.028mg/m^3)$ in leather $0.0039mg/m^3(0.003{\sim}0.005mg/m^3)$ in other by the type of industry and it exceeded TLV-TWA ($0.05mg/m^3$) in five (13.6%) of plating services. 2. The geometric mean of chromium in blood was $1.54{\mu}g/dl(0.10{\sim}3.62{\mu}g/dl)$ in Plantng, $0.94{\mu}g/dl(0.27{\sim}2.82{\mu}g/dl)$ in fabricated metal product, $0.51{\mu}g/dl(0.10{\sim}3.25{\mu}g/dl)$ in dyestuff, $0.87{\mu}g/dl(0.15{\sim}8.00{\mu}g/dl)$ in leather, $0.55{\mu}g/dl(0.20{\sim}2.28{\mu}g/dl)$ in other by the type of industry(p<0.001). 3. The geometric mean of chromium in urine was $14.47{\mu}g/l(6.90{\sim}28.00{\mu}g/l)$ in planting, $4.63{\mu}g/l(0.24{\sim}43.00{\mu}g/l)$ in fabricated metal product, $5.93{\mu}g/l(1.00{\sim}33.00{\mu}g/l)$ in dyestuff, $11.09{\mu}g/l(0.80{\sim}48.00{\mu}g/l)$ in leather, $12.41{\mu}g/l(10.10{\sim}41.00{\mu}g/l)$ in other by the type of industry(p<0.001). 4. As the result of nasal specular examination, twenty four cases (8.4%) of nasal septal perforation among 287 total subjects was observed, and there were 17 (9.7%) cases in plating, 4 csaes (14.3%) in dressing and dyeing of leather. In the comparison of chromium concentration in blood and urine between the perforated group and non-perforated group, the perforated group showed a significantly higher value as $1.883{\pm}3.055{\mu}g/dl\;and\;0.793{\pm}0.815{\mu}g/dl$(P<0.001), $21.31{\pm}34.610{\mu}g/L\;and\;9.304{\pm}11.079{\mu}g/L$ (P<0.001). 5. The mean concentration of chromium in blood, urine and the mean level of AST, ALT, Hb and Hct in exposure group were higher than those of control group(p<0.001).

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Efficacy of Intravenous Iron Sucrose for Treating Anemia after Gastrectomy (위절제술 후 빈혈에 있어서 Iron Sucrose의 효과)

  • Kwon, In-Gyu;Song, Jye-Won;Kang, Wook-Ho;Oh, Sung-Jin;Hyung, Woo-Jin;Choi, Seung-Ho;Noh, Sung-Hoon
    • Journal of Gastric Cancer
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    • v.8 no.4
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    • pp.262-266
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    • 2008
  • Purpose: Many patients suffer with anemia after gastrectomy. Iron deficiency due to a decreased oral intake and malabsoption is the most common cause of anemia in gastrectomized patients. This study evaluated the efficacy of administering intravenous iron sucrose for treating patients with anemia. Materials and Methods: From May 2007 to October 2007 at Yonsei University Severance Hospital, we reviewed 47 outpatients whose hemoglobin levels were below 11 g/dl after gastrectomy. Iron sucrose was used for iron supplementation. To determine the difference between before and after the treatment (at 1 week, 2 weeks, 3 weeks, 3 months and 6 months after treatment), we prospectively examined such anemia parameters as the hemoglobin level (Hgb), the hematocrit (Hct), serum iron, TIBC, ferritin and transferin. Results: Out of the 47 patients, only 36 completed their treatment. Eleven were male and 25 were female. The Hgb levels, which indicate anemia, were elevated 0.6, 0.8, 1.3, 2.1 and 2.2 g/dl after 1 week, 2 weeks, 3 weeks, 3 months and 6 months after administration, respectively (P<0.001). The changes from 1 week to 3 months were statistically significant, but those from 3 to 6 months were not. The Hgb levels of 26 patients, which accounted for 72% of all the patients, elevated up to 12 g/dl or more. No side effects or complications were found, but there was one case of temporary nausea. Conclusion: Anemia after gastrectomy is safely treated in a relatively short time with administering iron sucrose. The patients' Hgb levels are expected to increase in a week and keep increasing up to 3 months.

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Activity-guided Purification of N-benzyl-N-methyldecan-1-amine from Garlic and Its Antitumor Activity against CT-26 Colorectal Carcinoma in BALB/C Mice (활성추적분리법에 의해서 순수분리한 마늘 N-benzyl-N-methyldecan-1-amine이 CT-26 세포주 이식 BALB/C mice의 항암효과)

  • Seetharaman, Rajasekar;Choi, Seong Mi;Guo, Lu;Cui, Zheng Wei;Otgonbayar, Duuriimaa;Park, Ju Ha;Kwon, Young-Seok;Kwak, Jung Ho;Kwon, Young Hee;Min, Ji Hyun;Kang, Jum Soon;Choi, Young Whan
    • Journal of Life Science
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    • v.29 no.10
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    • pp.1062-1070
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    • 2019
  • A components of garlic (Allium sativum) have anti-proliferative effects against various types of cancer. We aimed to investigate the capacity of garlic compounds to anti-tumor on a various cancer cell lines. Fractionation of garlic extract, guided by antiproliferative activity against human gastric cancer (AGS) cells, has resulted in the isolation of N-benzyl-N-methyldecan-1-amine (NBNMA). We investigated the effect of newly isolated NBNMA from garlic cloves on the inhibition of the growth of CT-26, AGS, HepG2, HCT-116, MCF7, B16F10, and Sarcoma-180 cells for in vitro and CT-26 colon carcinoma cells in vivo. NBNMA exhibited an antiproliferative effect in CT-26 cells by apoptotic cell death. NBNMA exhibited down-regulation of anti-apoptotic Bcl-2 proteins and up-regulation of apoptotic Bad protein expression in western blot analyses. In addition, NBNMA meagre activated caspase 3 and caspase 9, initiator caspases of the extrinsic and intrinsic pathways of apoptosis. NBNMA treatment at a dose of 10 mg/kg for 21 days in experimental mice implanted with tumors resulted in significant reduction of the tumor weight (43%). NBNMA exhibited both in vitro and in vivo anticancer activity. These results indicate that NBNMA has promising potential to become a novel anticancer agent from garlic cloves for the treatment of colon carcinoma cancer.

Radiation Protection Effect of Blueberries in the Hematopoietic Cells of White Rats (흰쥐의 조혈세포에서 블루베리의 방사선 방호효과)

  • Lee, Jun-Haeng
    • Journal of the Korean Society of Radiology
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    • v.16 no.3
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    • pp.335-341
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    • 2022
  • The purpose of this study was to investigate the radiation protection effect of blueberries. The experimental animals used in this study were 8-week-old 21 SD male rats weighed 280-300 g. The animals were set to a normal group (A), a 5 Gy control group (B), and a 5 Gy experimental group (C) of seven rats each, and (50 mg/kg/day) of physiological saline solution of blueberries were orally administered twice a day with an oral dose of (200 mg/kg/day) for seven days and 5 Gy of radiation was irradiated in the case of groups B and C. As a result, it was identified that there was significance in white blood cells in this study (p<0.000). There was no significant difference in red blood cells or platelets. When examined in detail, among white blood cells (WBC), neutrocytes were found to be significantly different among the three groups: normal, control, and experimental groups (p<0.004). Lymphocytes were also found to be statistically significantly different among the three groups (p<0.000). Monocytes were not found to be statistically significantly different (p<0.483). When red blood cells (RBC) were examined, hemoglobin (HGB) was not found to be statistically significant different among the three groups (p<0.291). Hematocrit (HCT) was not found to be statistically significantly different among the three groups, either (p<0.564). Mean corpuscular volume (MCV) was found to be statistically significantly different among the three groups (p<0.001). Mean corpuscular hemoglobin (MCH) was also found to be statistically significantly among the three groups (p<0.028). Mean corpuscular hemoglobin concentration (MCHC) was found to be statistically significantly different among the three groups(p<0.020). Red blood cell distribution width (RDW) was not found to be statistically significantly different among the three groups (p<0.09). When platelets (PLT) were examined in detail, mean platelet volume (MpV) was found to be statistically significantly different among the three groups (MpV) (p<0.04). In conclusion, based on this study, blueberries are considered to have radiation protection effects.

Reversal of Multidrug Resistance with KR-30035: Evaluated with Biodistribution of Tc-99m MIBI in Nude Mice Bearing Human Tumor Xenografts (이종이식된 인체종양에서 KR-30035가 Tc-99m MIBI체내 분포에 미치는 영향으로 평가한 다약제내성 역전가능성)

  • Kim, Jung-Kyun;Lee, Byung-Ho;Choi, Sang-Woon;Yoo, Sung-Eun;Lee, Sang-Woo;Chun, Kyung-Ah;Ahn, Byeong-Cheol;Park, Jae-Young;Suh, Jang-Soo;Lee, Kyu-Bo;Lee, Jae-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.35 no.3
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    • pp.168-184
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    • 2001
  • Purpose: KR-30035 (KR), a new MDR reversing agent, has been found to produce a similar degree of increased Tc-99m MIBI uptake in cultured tumor cells over-expressing mdr1 mRNA compared to verapamil (VP), with less cardiovascular effects. We assessed the MDR-reversing ability of KR in vivo, and effects of various doses of KR on MIBI uptake un nude mice hearing P-glycoprotein (P-gp) positive (+) and P-gp negative (-) human tumor xenografts. Methods: P-gp (+) HCT15/CL02 colorectal and P-gp (-) A549 non-small cell cancer cells were inoculated in each flank of 120 nude mice (20 mice ${\times}$ 6 groups). Group 1 (Gr1) mice received 10mg/kg KR i.p. 3 times $({\times}3)$; Gr2, 10mg/kg VP i.p. ${\times}3$; Gr3, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.p. ${\times}1$; Gr4, 10mg/kg KR i.p. ${\times}2$ + 50mg/kg i.p. ${\times}1$; Gr5, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.v. ${\times}1$, GrC, controls. The mice were then injected with Tc-99m MIBI and sacrificed after 10 min, 30 min, 90 min and 240 min. Tumor uptake of MIBI (TU) in each group was compared. Results: TU in P-gp (+) and (-) tumors were both higher in Gr1 than Gr2. Washout rate between the 10 min and 4 hours was lower in Gr5 of P-gp (+) cell(0.93) than the control. Percentage increases in TU were higher in P-gp (+) than P-gp (-) tumors with all KR doses. Pgp (+) TU were highest at 10 mon (173% of GrC) and persisted up to 240 min (144%) in Gr3. Larger doses of KR resulted in a lesser degree of increase in P-gp (+) TU at 10 min (130% in Gr4 and 117% un Gr5) and 30 min (178%, 129%), but TU increased by time up to 240 min (177%, 196%). Heart and lung uptakes were markedly increased in Gr4 and Gr5 at 10 and 30 min, likely due to cardiovascular effects. No mice died. Conclusion: These data further suggest that KR that has significantly lower cardiovascular toxicity than verapamil can be used as an active inhibitor of MDR. Even a relatively low dose of KR significantly increased Tc-99m MIBI uptake in P-gp (+) tumors in vivo.

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Clinical Study of Corrosive Injury of the Esophagus (식도부식증의 임상적 고찰)

  • 박철원;송기준;이형석;안경성;김선곤
    • Proceedings of the KOR-BRONCHOESO Conference
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    • 1981.05a
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    • pp.5.3-6
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    • 1981
  • There are too many kinds of esophageal corrosive agents, such as sodium hydrochloride, acetic acid, hydrochloric acid, etc. Esophageal burn due to above chemical agents are decreasing recently, but still many patients visited to the hospital because of swallowing corrosive agents for the purpose of suicide or accidentally. Among the treatment of corrosive injury of the esophagus, prevention of esophageal stricture is the key point. Recently various methods are using as the treatment of corrosive esophagitis and prevention of esophageal stricture. 51 cases of corrosive injury of the esophagus who had been admitted and treated at the Dept. of Otolaryngology, Han Yang University Hospital during past 9 years (from May 1972 to Dec. 1980) were evaluated and report the result about age distribution, sex incidence, monthly distribution, cause of swallowing, swallowing agents, arriving time at hospital after swallowing, changes on oral and pharyngeal mucosa, laboratory findings, emergency treatment and treatment during admission, treatment follow up results and complications with review of liter ature. Following results were obtained; 1. Female patients 27 cases (52.9%) were more than male patients 24 cases (47.1%) and its ratio was 1.13 : 1. 2. Age distribution showed predilection for age of 21-30 with 20 cases(39.2%), and 11-20 with 11 cases (21.6%), 31-40 with 7 cases(13.7%), over 50 with 7 cases (13.7%) were following. 3. Monthly distribution showed predilection for March with 8 cases(15.7%), and April, July with 7 cases (13.7%), September with 6 cases(l1.8%), October 5 cases(9.8%) were following. 4. For the purpose of suicide was the most cause of swallowing with 40 cases(78.4%), and accidentally swallowing 11 cases(21.6%). 5. Acetic acid was the most swallowing agent with 24 cases (47.0%), and hydrochloric acid 11 cases (21.5%), lye 8 cases(15.7%), iodine 2 cases(3.9%) were following. 6. Arriving time at the hospital after swallowing showed predilection for within 12 hours with 42 cases (82.4%), and from 12 hours to 24 hours with 4 cases(7.8%) was next. 7. Moderate change with injection and swelling was the prevalent change on oral and pharyngeal mucosa with 20 cases(39.2%) and severe cases with ulceration 18 cases (35.3%), mild cases with injection 10 cases (19.6%) were following. 8. Leukocytosis was seen on 40 cases (78.4%), and increased Hct. was seen 31 cases (60.8%). On urine analysis, 14 cases(27.5%) showed over 1.030 S.G., and proteinuria was seen on 25 cases(49.0%), glycosuria was seen on 5 cases(9.8%) and hematuria was seen on 6 cases(11.8). 9. Gastric lavage was done on 30 cases (58.8%) as emergency treatment and on 3 cases(5.9%) tracheostomy was done for the airway keeping. 10. As methods of treatment during admission, L-tube insertion was done on 50 cases (98.0%), antibiotics was given to 49 cases (96.1%), steroid and antacid were given to 46 cases(90.2%). 11. 36 cases(70.6%) were in favorable condition after proper treatment, but 2 cases (3.9%) were expired during admission, 4 cases (7.8%) showed esophageal stricture in-spite of treatment, and 1 case(2.0%) showed pyloric stenosis. 12. Complications were observed in 8 cases (17.7%). Renal failure (4 cases), aspiration pneumonia (2 cases), upper G-I bleeding (1 cases), and diabetic coma (1 cases) were seen in order of frequency.

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Nonoperative Management of Blunt Liver Trauma (둔상성 간 손상환자의 비수술적 치료)

  • Baik, Jung Ju;Kim, Jung Il;Choi, Seung Ho;Choi, Young Cheol;Jun, Si Youl;Lee, Jun Ho;Hwang, Seong Youn
    • Journal of Trauma and Injury
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    • v.18 no.2
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    • pp.161-171
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    • 2005
  • Background: The management of hepatic injuries has changed dramatically during the past two decade after the technologic breakthroughs in radiologic imaging techniques. Recently, the non-operative management of blunt hepatic trauma has become the standard of care in hemodynamically stable patients. We reviewed our experience of the non-operative management of blunt hepatic trauma. And the purpose of this study was to examine the prognostic factors and indicators affecting the decision for treatment modality of emergent hepatic trauma. Methods: The medical records of 84 patients who were treated for blunt hepatic injury at Masan Samsung Hospital from January 2002 to December 2003. The patients were divided two groups, non-operative(Non-OP) and operative(OP), according to the treatment modality. The two groups were compares for age, sex, mechanism of injury, grade of liver injury scale, combined injury, systolic blood pressure, pulse rate, hemoglobin, hematocrit, WBC count, S-GOT, S-GPT, ALP, transfusion amount during initial 24 hours, amount of infused crystalloid fluid, length of ICU stay, length of ward care, morbidity and mortality. The grade of the liver injury were determined by using the organ injury scale(OSI). Results: Among the 84 patients, 46 cases(54.8%) were managed non-surgically, and 3 cases of Non-OP group were treated by transarterial embolization. Between the two groups, there were significant difference in age, injury grade, combined injury, hemoglobin, hematocrit, initial systolic blood pressure, amount of infused crystalloid fluid, amount of transfusion during the first 24 hours, and length of ICU care, morbidity and mortality.(p<0.05) The overall mortality rate was 8.3%, but 2.2% mortality in the non-operative group. Conclusion: Non-operative management may be considered as a first choice in hemodynamic stable patients with blunt liver trauma. The reliable indicators affecting the treatment modality of blunt hepatic trauma were systolic BP, Hb, Hct, amount of infused crystalloid fluid, amount of transfusion during the first 24 hours, liver injury grade and combined injury. Strict selection of treatment madality and aggresive monitoring with intensive care unit were more important.

Effects of Dietary L-carnitine Supplementation on Growth Performance, Organ Weight, Biochemical Parameters and Ascites Susceptibility in Broilers Reared Under Low-temperature Environment

  • Wang, Y.W.;Ning, D.;Peng, Y.Z.;Guo, Y.M.
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.2
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    • pp.233-240
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    • 2013
  • The objective of this study was to investigate the effects of L-carnitine on growth performance, organ weight, biochemical parameters of blood, heart and liver, and ascites susceptibility of broilers at different ages reared under a low-temperature environment. A total of 420 1-d-old male Ross 308 broilers were randomly assigned to two dietary treatments with fifteen replicates of fourteen broilers each. Treatment diets consisted of L-carnitine supplementation at levels of 0 and 100 mg/kg. At 11-d of age, low temperature stress was used to increase ascites susceptibility. Blood, heart and liver samples were collected at different ages for analysis of boichemical parameters. The results showed that, there was no significant difference in growth performance with L-carnitine supplementation, but the mortality due to ascites was significantly decreased. Dietary L-carnitine supplementation significantly reduced heart index (HI) and ascites heart index (AHI) on d 21, lung index (LUI) on d 35 and liver index (LI) on d 42. The broilers fed diets containing L-carnitine had significantly lower red blood cell counts (RBC), hemoglobin (HGB) concentration and hematocrit (HCT) on d 42. Dietary L-carnitine supplementation significantly reduced malondialdehyde (MDA) content of heart tissue on d 21 and 35, and significantly increased total superoxide dismutase (T-SOD) and Glutathione peroxidase (GSH-Px) activity of the heart on d 21 and 42. L-carnitine supplementation significantly reduced serum triglyceride (TG) content on d 28 and 35 and serum glucose (GLU) on d 35 and 42, and significantly increased serum total protein (TP) and globulin (GLO) content on d 42. L-carnitine supplementation significantly enhanced liver succinodehydrogenase (SDH), malic dehydrogenase (MDH) and $Na^+$-$K^+$-ATPase activity on d 28, and tended to reduce the lactic acid (LD) level of liver on d 35 (p = 0.06). L-carnitine supplementation significantly reduced serum uric acid (UA) content on d 28, 35 and 42. Based on the current results, it can be concluded that dietary L-carnitine supplementation reduced organ index, red blood cell counts and hematocrit, enhanced antioxidative capacity of the heart, enhanced liver enzymes activity involved in tricarboxylic acid cycle, and reduced serum glucose and triglyceride. Therefore, it is suggested that L-carnitine can potentially reduce susceptibility and mortality due to ascites.

Evaluation of Cytotoxicity, Antimicrobial and Antioxidant Enzyme Activity of Diploid and Tetraploid Platycodon grandiflorum

  • Boo, Hee-Ock;Kim, Young-Sun;Kim, Hag-Hyun;Kwon, Soo-Jeong;Woo, Sun-Hee
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.60 no.2
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    • pp.239-247
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    • 2015
  • This experiment was conducted to obtain the have higher contents of pharmaceutical constituents as well as higher yield from colchicine induced diploid and tetraploid extracts of Platycodon grandiflorum. In order to determine the biological activity, this study was focused to evaluate the cytotoxicity, antimicrobial on the bronthus disease bacteria, antioxidant enzyme activity of diploid and tetraploid extracts in P. grandiflorum. The activities of antioxidant enzyme according to different solvent extracts were measured as superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX). The cytotoxicity of methanol extracts of P. grandiflorum showed significant differences between tetraploid and diploid. That is, the cytotoxic effect against human cancer cell was higher in tetraploid than in diploid. At all extracts concentration, tetraploid samples showed high toxicity and the $IC_{50}$ (concentration causing 50% cell death) value showed the highest on HCT-116 cell ($105.91{\mu}g/mL$), and exhibited significant activity against the Hep 3B cell ($140.67{\mu}g/mL$), SNU-1066 cell ($154.01{\mu}g/mL$), Hela cell ($158.37{\mu}g/mL$), SNU-601 cell ($182.67{\mu}g/mL$), Calu-6 cell ($190.42{\mu}g/mL$), MCF-7 cell ($510.19{\mu}g/mL$). Antimicrobial activities of diploid P. grandiflorum were relatively low compared to tetraploid P. grandiflorum on most of the bacterial strains. In tetraploid P. grandiflorum, K. pneumoniae showed the clear zone formation (18~19 mm) of growth inhibition, followed by the clear zone formation of 13~15 mm on C. diphtheria and S. pyogenes. The antimicrobial activities in diploid P. grandiflorum were the highest on K. pneumonia (14~15 mm), and showed the clear zone formation of 11~12 mm on C. diphtheria and 12~13 mm on S. pyogenes. The antimicrobial activity is thought to look different depending on the bacterial strains and the polyploidy of P. grandiflorum. The root extract of P. grandiflorum had the highest (97.2%) SOD enzyme activity in ethyl acetate partition layer of tetraploid while water partition layer of diploid showed the lowest (48.6%) SOD enzyme activity. The activity of CAT showed higher values in the root of tetraploid than in the diploid of P. grandiflorum in all partition layers except butyl alcohol. The activities of APX and POD showed higher values in the root of tetraploid than in the diploid of P. grandiflorum in all fraction solvents except water layer. These results indicate that the tetraploid P. grandiflorum can be used as a source for developing cytotoxic agent and antimicrobials which can act against bronchus diseases bacterial strains.

Antitunor Effect of Carcinoma cells Ttransduced with Herpes simplex virus-thymidine kinase by Gancyclovir and Radiation (Herpes simplex virus-thymidine kinase 유전자가 전이된 종양 세포에서 Gancyclovir와 방사선 조사에 의한 항 종양 효과)

  • Lee, Jae Woo;Oh, Seong Taek;Ahn, Chan Hyuk;Lim, Kun Woo;Cho, Hyun-Il;Kim, Gum Ryong;Kim, Tai-Gyu
    • IMMUNE NETWORK
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    • v.1 no.1
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    • pp.45-52
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    • 2001
  • Background: Many types of cancer become resistant to current chemotherapeutic and radiotherapeutic intervention. To overcome this situation application of gene therapy by the introduction of suicide genes followed by their prodrugs may be promising. A viral enzyme, Herpes simplex thymidine kinase (HSV-tk), which converts ganciclovir from an inactive prodrug to a cytotoxic agent by phosphorylation, are being actively investigated for use in gene therapy for cancer. The purpose of this study was to determine whether combining prodrug-activating gene therapy and irradiation might result in enhanced antitumor effects. Methods: The HSV-tk gene was cloned into the retroviral vector, pLXSN and established the clones producing retroviruses carrying the HSV-tk gene. The carcinoma cell line, HCT116 and Huh-7 were transduced with high-titer recombinant retroviruses. These cell lines were treated with ganciclovir before or after irradiation for the defining combinational effect of suicide gene therapy and radiotherapy. Results: The titers of cloned PA3 17 amphotropic retroviruses ranged from 4 to 6 X $10^6CFU/ml4$. After selectional periods, the expression of HSV-tk was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). The growth of cells expressing HSV-tk was inhibited as increase of GCV dose after 48 hr and the growth inhibitory effect of GCV was much higher after 72 hr. When the cells transduced with HSV-tk gene were exposed to radiation, the growth inhibitory effect of GCV was significantly increased, as compared with non-transduced parental cells. Conclusions: The results suggest that the addition of HSV-tk gene therapy to standard radiation therapy may improve the effectiveness of treatment for solid tumors.

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