• Title/Summary/Keyword: Dose toxicity study

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Radiotherapy in Incompletely Resected Gastric Cancers (불완전 절제된 위암의 방사선 치료)

  • Kim Jong Hoon;Choi Eun Kyung;Cho Jung Gil;Kim Byung Sik;Oh Sung Tae;Kim Dong Kwan;Chang Hyesook
    • Radiation Oncology Journal
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    • v.16 no.1
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    • pp.17-25
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    • 1998
  • Purpose : Although local recurrence rates of stomach cancer after radiocal surgery have been reported in the range of $30-70\%$, the role of postoperative adjuvant therapy has not been established. We report the result of radiotherapy in resected stomach cancer with positive surgical margin to elucidate the role of postoperative radiotherapy. Materials and Methods : From June 1991 to August 1996, twenty five patients with positive surgical margins after radical gastrectomy were treated with postoperative radiotherapy and chemotherapy. Median dose of radiation was 55.8Gy and the range was 44.6-59.4Gy. Second cycle of chemotherapy was delivered concurrently with radiation and total number of six cycles were delivered. Twenty three had adenocarcinoma and the other two had leiornyosarcoma. The numbers of patients with stage I B, II, III A, III B, and IV were 1, 2, 11, 10 and 1 respectively. Positive margins at distal end of the stomach were in 17 patients and proximal in 5. The other three patients had positive margin at the sites of adjacent organ invasion Minimum and median follow-up periods were 12 months and 18 months, respectively, Results : Twenty-four of 25 patients received prescribed radiation dose and RTOG grade 3 toxicity of UGI tract was observed in 3, all of which were weight loss more than $15\%$ of their pretreatment weight. But hematemesis. melena, intestinal obstruction or grade 4 toxicity were not found. Locoregional failure within the radiation field was observed in 7 patients, and distant metastasis in 10 patients. Sites of locoregional recurrences involve anastomosis/remnant stomach in 3, tumor bed/duodenal stump in 3, regional lymph node in 1 patient Peritoneal seeding occurred in 6, liver metastases months and median disease free survival time was 26 months. Stages andradiation dose were not significant prognostic factors for locoregional in 2, and distant nodes in 2 patients. Four year disease specificsurvival rate was $40\%$ and disease free survival was $48\%$. Median survival was 35 failures. Conculsion : Although all patients in this study had positive surgical margins, locoregional failure rate was $28\%$, and 4 year disease specific survival rate was $40\%$. Considering small number of patients and relatively short follow-up period, it is not certain that postoperative radiotherapy lowered locoregional recurrences. but we could find a Possibility of the role of postoperative radiotherapy in Patients with high risk factors.

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Analysis of PAHs (polycyclic aromatic hydrocarbons) in Ground Coffee Using GC-tandem Mass Spectrometry and Estimation of Daily Dose (GC-tandem mass spectrometry를 이용한 분쇄원두커피 중 PAHs(polycyclic aromatic hydrocarbons) 분석법 연구 및 인체노출량 평가)

  • Jung, So-Young;Park, Ju-Sung;Son, Yeo-Joon;Choi, Su-Jeong;Lee, Yun-Jeong;Kim, Mi-Sun;Park, So-Hyun;Lee, Sang-Me;Chae, Young-Zoo
    • Korean Journal of Food Science and Technology
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    • v.43 no.5
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    • pp.544-552
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    • 2011
  • The purpose of this study was to develop an analytical method for determining 15 polycyclic aromatic hydrocarbons (PAHs) of EU priority using gas chromatography (GC)-tandem mass spectrometry (MS). The PAHs in ground coffee were analyzed after being extracted using methods such as saponification-liquid-liquid extraction, Soxhlet extraction, and solid-liquid extraction. The solid-liquid extraction method showed the greatest repeatability and most efficient reduction of the matrix effect. GC-tandem MS for the quantification of the 15 PAHs showed better resolution and lower limit of detections (LODs) than GC-MS-selected ion monitoring (SIM) and high performance liquid chromatography with fluorescence detector. LODs of this method for the ground coffee types were 0.002-0.1 ${\mu}g/kg$ and limit of quantifications (LOQs) were 0.006-0.2 ${\mu}g/kg$ The recoveries ranged from 52.6 to 93.3%. Forty-six commercial types of ground coffee were analyzed to determine their PAHs contamination levels. PAHs concentration ranged from ND to 5.988 ${\mu}g/kg$. This study was conducted with toxicity equivalence factors, the U.S. EPA recommendation to identify dietary risks for PAHs in different types of coffee. The estimated average daily dose of PAHs was $5.24{\times}10^{-8}$ mg/kg body weight/day.

The Efficacy of Immediate Diet for Reducing Local Adverse Events of Inhaled Corticosteroid: A Pilot Study

  • Lee, Myoung Kyu;Lee, Won Yeon;Yong, Suk Joong;Shin, Kye Chul;Kim, Chong Whan;Lee, Ji-Ho;Jung, Saehyun;Jung, Ye-Ryung;Kim, Hyun Sik;Yu, Tae-Sun;Kim, Sang-Ha
    • Tuberculosis and Respiratory Diseases
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    • v.73 no.2
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    • pp.93-99
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    • 2012
  • Background: Local adverse events associated with inhaled corticosteroid use, including dysphonia, pharyngitis and oral candidiasis, can affect adherence for treatment. 'Mouth rinsing method' has been used for reducing local adverse events, but it cannot ensure complete prevention. The goal of this pilot study was to identify whether the 'immediate diet method' can reduce local adverse events in a limited number of patients. Methods: The study was conducted in a total of 98 patients, who had been prescribed a medium-dose fluticasone propionate for the first time, from January to October in 2010. One training nurse had performed the education on how to use the inhaler, including the mouth rinsing method. And with follow-ups at one month intervals, any patient who experienced such adverse events were educated on the immediate diet method, having a meal within 5 minutes after using an inhaler and they were checked on any incurrence of adverse events with one month intervals for 2 months. Results: The mean age of patients was 65.9 years old. The local adverse events had incurred from 18.4% of the study subjects. When performed the follow-up observation in 18 patients with local adverse events after education on the immediate diet method, 14 patients (77.8%) had shown symptomatic improvements. Three of 4 patients did not show any improvement, in spite of implementing the immediate diet method. The other 1 patient did not practice the immediate diet method properly. Conclusion: The immediate diet method may be useful in reducing the local adverse events, caused by the use of inhaled corticosteroid.

Protective Effects of Lespedeza bicolor Extract on B16/F10 Melanoma Cell Lines Damaged by Lead Acetate, Heavy Metal Compounds (중금속 화합물인 초산납으로 손상된 B16/F10 멜라닌세포주에 대한 싸리나무 추출물의 보호 효과)

  • Seo, Young-Mi
    • Korean Journal of Clinical Laboratory Science
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    • v.53 no.4
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    • pp.363-370
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    • 2021
  • This study was conducted to evaluate the dermal cytotoxicity of lead acetate (LA) and other heavy metal compounds, and the protective effect of Lespedeza bicolor (LB) extract on LA-induced cytotoxicity in cultured B16-/F10 melanoma cells. The study evaluated the antioxidative effects of LB due to its electron-donating ability (EDA), inhibitory effects on melanization and improving cell viability. LA significantly decreased cell viability in a dose-dependent manner, and the XTT50 value was determined at 52.7 µM in the studied cultures. Based on the Borenfreund and Puerner's toxicity criteria, LA was estimated to be highly cytotoxic. LA-induced cytotoxicity and cell damage was reversed by the antioxidant activity of kaempferol (KAE), thereby remarkably improving cell viability. A study of the protective effects of the LB extract on LA-induced cytotoxicity showed that the LB extract remarkably increased cell viability in the LA-treated group, and also inhibited the EDA and the total amount of melanin. The above results suggest oxidative stress-mediated cytotoxicity of LA. In the study, LB extract effectively prevented LA-induced cytotoxicity via its antioxidative activity and inhibition of melanization. In conclusion, natural resources like LB extracts may be useful agents for the prevention of oxidative stress-mediated cytotoxicity and melanization by heavy metallic compounds such as LA.

A 4-Week Oral Toxicity Study of 2-Bromopropane in Sprague- Dawley Male Rats (2-Bromopropane의 수컷 랫트를 이용한 4주간 반복 경구투여 아급성독성실험)

  • 이현숙;강부현;손화영;김희연;조영채;노정구
    • Toxicological Research
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    • v.14 no.2
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    • pp.129-141
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    • 1998
  • Toxic effects of 2-bromopropane (2-BP) on the hematopoietic system and testis were investigated in male Srague-Dawley (SD) rats. 80 male SD rats, 5 weeks old, were treated with 2-BP in corn oil at levels of 0, 100, 330 and 1,000 mg/kg/day for 4 weeks orally. 10 animals from each group were maintained for additional 8 weeks following the treatment. In addition, 60 male SD rats were divided into 2 groups and administered 2-BP in corn oil at levels of 0 and 1,000 mg/kg/day orally and sacrificed after 1. 2 and 3 weeks of treatment. Clinical observation. body weight changes, food consumption, organ weight changes. hematology, serum chemistry and histopathology of the testis were performed in the study. No clinical sign and mortality were observed in the study. The body weights were significantly reduced with the treatment but gradually recovered. The relative organ weights of the testis and thymus significantly decreased in both of the groups treated with 1,000 mg/kg/day for 3 and 4 weeks. In the recovery groups, organ weights of the testis and epididymis were significantly reduced in both of the groups treated with 330 and 1,000 mg/kg/day. Platelets and reticulocytes were significantly reduced in both of the group treated with 1.000 mg/kg/day for 3 and 4 weeks. While red blood cells were de-creased but mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were increased in the recovery group. Significant increase of chloride was observed in all of the treatment groups except the recovery groups, and calcium was significantly increased in both of the groups treated with 1,000 mg/kg/ day for 3 and 4 weeks. On the other hand. there were significant decreases in alanine aminotransferase (ALT) and aspatate aminotransferase (AST) in most of groups treated with 1.000 mg/kg/day. In the testis. the spermatogonia in stages I-VI were mostly depleted and the spermatocytes in stages VII-VIII were de-generated or necrotized at week 1 after treatment of 2-BP. The degeneration of germ cells and the a-trophy of seminiferous tubules became more severe in time-dependent and dose-dependent manners. The damaged tubules showed regeneration in part. however. they did not appear to be completely recovered within 8 weeks of the recovery period. On the basis of the results. it is suggested that 2-BP would cause toxicities in hematopoiesis by possibly interfering the production of red blood cells and platelets and in spermatogenesis by the destruction oj spermatogonia in SD male rats.

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Study on the Chemical Management - 1. Chemical Characteristics and Occupational Exposure Limits under Occupational Safety and Health Act of Korea (화학물질 관리 연구-1. 산업안전보건법상 관리 화학물질의 특성과 노출기준 비교)

  • Park, Jihoon;Ham, Seunghon;Kim, Sunju;Lee, Kwonseob;Ha, Kwonchul;Park, Donguk;Yoon, Chungsik
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.25 no.1
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    • pp.45-57
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    • 2015
  • Objectives: This study aims to compare the physicochemical characteristics, toxicological data with Occupational Exposure Limits (OELs) of chemicals under the Occupational Safety and Health Act(OSHA) regulated by the Ministry of Employment and Labor of Korea. Methods: Information on chemicals which have OELs on physicochemical characteristics and toxicological data was collected using Material Safety Data Sheet(MSDS) from Korea Occupational Safety and Health Agency(KOSHA) and the Korea Information System for Chemical Safety Management(KISChem) in 2014. Statistical analyses including correlation and simple regression were performed to compare the OELs with chemical characteristics including molecular weight, boiling point, odor threshold, vapor pressure, vapor density, solubility and octanol-water partition coefficient(OWPC) and toxicological data such as median lethal dose($LD_{50}$) and median lethal concentration($LC_{50}$). Results: A total of 656 chemicals have OELs under OSHA in Korea. The numbers of chemicals which have eight-hour time weighted average(TWA) and short term exposure limits(STEL) are 618 and 190, respectively. TWA was significantly correlated with boiling point and STEL was only correlated with vapor pressure among physicochemical characteristics. Solubility and OWPC between "skin" and "no skin" substances which indicate skin penetration were not significantly different. Both $LD_{50}$ and $LC_{50}$ were correlated with TWA, while the $LC_{50}$ was not with STEL. As health indicators, health rating and Emergency Response Planning Guidelines(ERPG) rating as recommended by the National Fire Protection Association(NFPA) and American Industrial Hygiene Association(AIHA) were associated with OELs and reflect the chemical hazards. Conclusions: We found relationships between OEL and chemical information including physicochemical characteristics and toxicological data. The study has an important meaning for understanding present regulatory OELs.

Protective effects of extracts from the aerial parts of hydroponically cultured ginseng on alcohol-induced liver damage in mice and quantitative analysis of major ginsenosides (알코올성 간손상을 유발한 마우스 모델에서의 새싹인삼 지상부 추출물의 간 기능 보호효과 및 지표성분 함량분석)

  • Lee, Mi Kyoung;Jang, In-Bae;Lee, Min Ho;Lee, Dae Young
    • Journal of Applied Biological Chemistry
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    • v.63 no.4
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    • pp.413-420
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    • 2020
  • We studied the effects of the extract of aerial parts of hydroponically cultured ginseng (HGE) on alcohol-induced liver damage (AILD) in mice. AILD was induced by the oral administration of ethanol (EtOH) (25%; 5 g/kg body weight) for seven days in the study as well as EtOH-only groups. However, HGE (4 and 12 mg/kg) was orally administered (once daily for ten consecutive days) only to the study group, three days prior to the EtOH treatment. The HGE-treated group showed significantly lower levels of alanine aminotransferase and aspartate aminotransferase than the EtOH-only group. In addition, HGE administration decreased the level of serum lactate dehydrogenase, a known marker of liver damage. The effect of HGE on AILD was found to be dose dependent, and the consecutive administration of HGE showed no side effects in mice. Our study indicates that HGE treatment can potentially reduce oxidative stress and toxicity in the liver of alcohol-treated mice and that HGE can be a useful therapeutic agent for alcohol-induced hepatotoxicity. Additionally, a simple and efficient high-performance liquid chromatography-ultraviolet detection method was developed for determining the contents of four major ginsenosides in HGE. The aerial parts of hydroponically cultured ginseng were extracted using 70% fermented ethanol, and the contents of ginsenosides F5, F3, F1, and F2 in HGE were found to be 2.5, 4.4, 1.4, and 23.3 mg/g, respectively.

Phytic Acid Protects the Formation of Colonic Aberrant Crypt Foci Induced by Azoxymethane in Male F344 Rats (랫드에서 azoxymethane으로 유도된 대장 전암병변에 대한 피티산의 방어 효과)

  • Hue, Jin-Joo;Lee, Yea-Eun;Lee, Ki-Nam;Nam, Sang-Yoon;Ahn, Byeong-Woo;Yun, Young-Won;Lee, Beom-Jun
    • Journal of Food Hygiene and Safety
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    • v.23 no.3
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    • pp.264-270
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    • 2008
  • Phytic acid(PA) (Inositol hexaphosphate, $IP_6$) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plants and mammalian cells. Recently PA has received much attention for its role in anticancer activity. In the present study, the preventive effects of PA on colon carcinogenesis were investigated. Six-week old Fisher 344 male rats were fed a AIN-93G purified diet and PA(0.5% or 2% PA in water) for 8 weeks. The animals received two ($1^{st}\;and\;2^{nd}$ week) injections of azoxymethane(AOM, 15 mg/kg b.w.) to induce colonic aberrant crypt foci(ACF). After sacrifice, the total numbers of aberrant crypts(AC) and ACF in colonic mucosa were examined after staining with methylene blue. Blood and serum were analyzed with a blood cell differential counter and an automatic serum analyzer. AOM induced the total numbers of $142.3{\pm}22.3$ ACF/colon and $336.6{\pm}55.1$ AC/colon. PA at the doses of 0.5 and 2% decreased the numbers of ACF and AC/colon in a dose-dependent manner. The numbers of ACF/colon and AC/colon by PA at the dose of 0.5% were $124.4{\pm}28.5\;and\;302.7{\pm}67.3$, respectively. PA at the dose of 2% significantly decreased the ACF and AC numbers to $109{\pm}18.1\;and\;254.8{\pm}50.6$, respectively(p<0.01). Especially, 2% PA significantly reduced the number of large ACF(${\geq}4$ AC/ACF) from $26.8{\pm}6.2$ ACF/colon to $15{\pm}6.7$ ACF/colon(p<0.01). Although some parameters in blood counts and serum chemistry were changed compared with the control, no specific toxicity was found. These findings suggest that phytic acid can be a chemopreventive agent for colon carcinogenesis resulting from inhibition of the development of ACF in the F344 rat.

Anti-Inflammatory Effect of Ethanol Extract from Onion (Allium cepa L.) Peel on Lipopolysaccharide-Induced Inflammatory Responses in RAW 264.7 Cells and Mice Ears (LPS로 유도된 RAW 264.7 세포와 마우스 귀 조직에 대한 양파(Allium cepa L.) 껍질 에탄올 추출물의 항염증 효과)

  • Ahn, Na-Kyung;Kang, Bo-Kyeong;Kim, Koth-Bong-Woo-Ri;Kim, Min-Ji;Bae, Nan-Young;Park, Ji-Hye;Park, Sun-Hee;Ahn, Dong-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.11
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    • pp.1612-1620
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    • 2015
  • Inflammation is a complex process involving a variety of immune cells, which defend the body from harmful stimuli. However, pro-inflammatory cytokines and inflammatory mediators can also exacerbate diseases such as cancer. Onion peel contains several phenolic compounds, including quercetin at an amount 20 times greater in peel than edible flesh. Therefore, in this study, the anti-inflammatory effects of onion peel ethanol extract (OPEE) were investigated lipopolysaccharide-induced inflammatory response. In our results, NO production decreased in a dose-dependent manner. Secretion of IL-6, $TNF-{\alpha}$, and $IL-1{\beta}$ was suppressed by 44%, 53%, and 60% respectively, at $100{\mu}g/mL$. Moreover, OPEE also suppressed expression of COX-2, iNOS, $NF-{\kappa}B$, and MAPKs in a dose-dependent manner. Formation of mice ear edema was reduced at the highest dose tested compared to the control, and reduction of ear thickness was observed in the histological analysis as well. In the acute toxicity test, no morality was observed in mice administered 5,000 mg/kg body weight of OPEE over a 2-week observation period. These results suggest that OPEE may have significant effects on inflammatory factors and be a potential anti-inflammatory material.

Study on the Chemical Management - 2. Comparison of Classification and Health Index of Chemicals Regulated by the Ministry of Environment and the Ministry of the Employment and Labor (화학물질 관리 연구-2. 환경부와 고용노동부의 관리 화학물질의 구분, 노출기준 및 독성 지표 등의 특성 비교)

  • Kim, Sunju;Yoon, Chungsik;Ham, Seunghon;Park, Jihoon;Kim, Songha;Kim, Yuna;Lee, Jieun;Lee, Sangah;Park, Donguk;Lee, Kwonseob;Ha, Kwonchul
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.25 no.1
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    • pp.58-71
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    • 2015
  • Objectives: The aims of this study were to investigate the classification system of chemical substances in the Occupational Safety and Health Act(OSHA) and Chemical Substances Control Act(CSCA) and to compare several health indices (i.e., Time Weighted Average (TWA), Lethal Dose ($LD_{50}$), and Lethal Concentration ($LC_{50}$) of chemical substances by categories in each law. Methods: The chemicals regulated by each law were classified by the specific categories provided in the respective law; seven categories for OSHA (chemicals with OELs, chemicals prohibited from manufacturing, etc., chemicals requiring approval, chemicals kept below permissible limits, chemicals requiring workplace monitoring, chemicals requiring special management, and chemicals requiring special heath diagnosis) and five categories from the CSCA(poisonous substances, permitted substances, restricted substances, prohibited substances, and substances requiring preparation for accidents). Information on physicochemical properties, health indices including CMR characteristics, $LD_{50}$ and $LD_{50}$ were searched from the homepages of the Korean Occupational and Safety Agency and the National Institute of Environmental Research, etc. Statistical analysis was conducted for comparison between TWA and health index for each category. Results: The number of chemicals based on CAS numbers was different from the numbers of series of chemicals listed in each law because of repeat listings due to different names (e.g., glycol monoethylether vs. 2-ethoxy ethanol) and grouping of different chemicals under the same serial number(i.e., five different benzidine-related chemicals were categorized under one serial number(06-4-13) as prohibited substances under the CSCA). A total of 722 chemicals and 995 chemicals were listed at the OSHA and its sub-regulations and CSCA and its sub-regulations, respectively. Among these, 36.8% based on OSHA chemicals and 26.7% based on CSCA chemicals were regulated simultaneously through both laws. The correlation coefficients between TWA and $LC_{50}$ and between TWA and $LD_{50}$, were 0.641 and 0.506, respectively. The geometric mean values of TWA calculated by each category in both laws have no tendency according to category. The patterns of cumulative graph for TWA, $LD_{50}$, $LC_{50}$ were similar to the chemicals regulated by OHSA and CCSA, but their median values were lower for CCSA regulated chemicals than OSHA regulated chemicals. The GM of carcinogenic chemicals under the OSHA was significantly lower than non-CMR chemicals($2.21mg/m^3$ vs $5.69mg/m^3$, p=0.006), while there was no significant difference in CSCA chemicals($0.85mg/m^3$ vs $1.04mg/m^3$, p=0.448). $LC_{50}$ showed no significant difference between carcinogens, mutagens, reproductive toxic chemicals and non-CMR chemicals in both laws' regulated chemicals, while there was a difference between carcinogens and non-CMR chemicals in $LD_{50}$ of the CSCA. Conclusions: This study found that there was no specific tendency or significant difference in health indicessuch TWA, $LD_{50}$ and $LC_{50}$ in subcategories of chemicals as classified by the Ministry of Labor and Employment and the Ministry of Environment. Considering the background and the purpose of each law, collaboration for harmonization in chemical categorizing and regulation is necessary.