• 제목/요약/키워드: dose assessment

검색결과 989건 처리시간 0.034초

구미 불산 누출사고 지점 주변 식물의 불소화합물 농도 분포 및 공기 중 불화수소 농도 추정에 관한 연구 (Study on the Distribution of Fluorides in Plants and the Estimation of Ambient Concentration of Hydrogen Fluoride Around the Area of the Accidental Release of Hydrogen Fluoride in Gumi)

  • 구슬기;최인자;김원;선옥남;김신범;이윤근
    • 한국환경보건학회지
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    • 제39권4호
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    • pp.346-353
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    • 2013
  • Objectives: The goal of this study is to identify the distribution of the foliar fluorine content of vegetation surrounding the area where hydrofluoric acid was accidently released in Gumi, Gyeongsangbuk-do on September 27, 2012. In addition, it also aims to estimate the concentration of hydrogen fluoride in the air on the day of the accident. Methods: Samples of plant leaves were collected on October 7, 2012 within 1 km from the site where the accident occurred. These samples were analyzed for soluble fluorine ion with an ion selective electrode. The ambient concentration of hydrogen fluoride was calculated using the fluoride content in the plant via the dose-rate equation (${\Delta}F$=KCT). Results: The arithmetic and geometric means of the concentrations were 2158.2 and 1183.7mg F $kg^{-1}$ for leaves and, 2.4 and 1.1 ppm HF for the air, respectively. The highest concentration of hydrogen fluoride in the air was 14.7 ppm, which is higher than the maximum concentration reported by the government (1 ppm) and the exposure limit (ceiling, 3 ppm). The concentrations of both fluorine and hydrogen fluoride decreased with increasing distance from the accident site and showed a significant decrease outside of a 500m radius from the site (p <0.05). Conclusions: The area around the accident site was highly polluted with hydrogen fluoride according to the results of this study. Considering the persistency of hydrogen fluoride in the environment, long-term monitoring and environmental impact assessment should be pursued.

섬망 환자에서 Quetiapine과 Haloperidol의 치료 효과 비교 : 전향적, 무작위 연구 (Comparison on the Efficacy of Quetiapine Versus Haloperidol in the Treatment of Delirium : Prospective, Randomized Trial)

  • 이유진;정한용;이소영;김신겸;박준호
    • 생물정신의학
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    • 제16권1호
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    • pp.15-24
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    • 2009
  • Objectives : The purpose of this study is to examine the efficacy and side effects of quetiapine and haloperidol for the treatment of symptoms of delirium. Methods : One hundred and seven patients with delirium were recruited and randomly assigned to receive a flexible-dose regimen of quetiapine or haloperidol over 7days and seventy-seven patients completed the study(quetiapine group N=40, haloperidol group N=37). The severity of delirium was assessed by using Memorial Delirium Assessment Scale(MDAS) scores, the psychiatric and behavioral symptoms were assessed by Neurobehavioral Rating Scale(NRS) scores, and the cognitive status was measured by Mini-mental state examination Korean version(MMSE-K) scores. The side effects were measured by Drug Induced Extrapyramidal Symptoms Scale(DIEPSS) scores. Results : MDAS scores significantly improved in both treatment groups. NRS scores also significantly improved in both treatment group, but the group-by-time effect approached significance, likely caused by the greater decrease in scores of the quetiapine group. MMSE-K scores significantly improved only in the quetiapine group. Side effects associated with treatment were not significant in either treatment groups. Conclusion : This study suggests that quetiapine is as efficacious as haloperidol in the treatment of delirium. In particular, quetiapine seems to improve psychiatric and behavioral problems of delirium and was more effective than haloperidol in cognitive improvement.

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Contributions of CYP2C9/CYP2C19 Genotypes and Drug Interaction to the Phenytoin Treatment in the Korean Epileptic Patients in the Clinical Setting

  • Lee, Soo-Youn;Lee, Seung-Tae;Kim, Jong-Won
    • BMB Reports
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    • 제40권3호
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    • pp.448-452
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    • 2007
  • We examined the contribution of CYP2C9 and CYP2C19 genotypes and drug interactions to the phenytoin metabolism among 97 Korean epileptic patients to determine if pharmacogenetic testing could be utilized in routine clinical practice. The CYP2C9 polymorphism is a wellknown major genetic factor responsible for phenytoin metabolism. The CYP219 polymorphism, with a high incidence of variant alleles, has a minor influence on phenytoin treated Koran patients. Using a multiple regression model for evaluation of the CYP2C9 and CYP2C19 genotypes, together with other non-genetic variables, we explained 39.6% of the variance in serum phenytoin levels. Incorporation of genotyping for CYP2C9 and CYP2C19 into a clinical practice may be of some help in the determination of phenytoin dosage. However, because concurrent drug treatment is common in patients taking phenytoin and many environmental factors are likely to play a role in drug metabolism, these factors may overwhelm the relevance of CYP polymorphisms in the clinical setting. Further investigations with an approach to dose assessment that includes comprehensive interpretation of both pharmacogenetic and pharmacokinetic data along with understanding of the mechanism of drug interactions in dosage adjustment is warranted.

Benzo(a)pyrene-Triglyceride Adduct: a Potential Molecular Biomarker for Carcinogen Exposure

  • Lee, Byung-Mu
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2002년도 국제심포지움
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    • pp.20-45
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    • 2002
  • In this study, we demonstrated the in vitro and in vivo formation of carcinogen-lipid adduct and its correlation with DNA or protein adducts. The lipids from serum or hepatocyte membranes of Spragu-Dawley rats. human serum, and standard major lipids were in vitro reacted with benzo[a]pyrene(BP) and BP metabolites. 7,8-Dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]-pyrene(BPDE-I), an ultimate carcinogenic form of BP, was covalently bound to triglyceride(TG). BPDE-I-TG adducts isolated by thin-layer chromatography (TLC) were further detected by high performance liquid chromatography(HPLC). TGs, including triolein, tripalmitin and tristearin, showed positive reactions with BPDE-I. However, cholesterol, phospholipids(Phosphatidylcholine, phosphatidyl-ethanolamine, phosphatidyl-inositol and sphingomyelin) and nonesterified fatty acids(palmitic acid, oleic acid, linoleic acid and stearic acid) did not react with BPDE-I. In addition, other BP metabolites (BP-phenols and -diols) did not react with TG, which TG appeared to be the most reactive lipid yet studied with respect to its ability to form an adduct with BPDE-I. There was a clear-cut dose-respect to its ability to form an adduct with BPDE-I-lipid adduct in vitro between TG and [1,3-3H]BPDE-I. In an animal study, BPDE-I-TG was also formed in the serum of rats orally treated with BP(25 mg/rat). Also, obvious correlations between [3H]BP related-biomolecule adducts (DNA, protein) or lipid damage and the BPDE-I-TG adduct were obtained in various tissues of mice i.p. treated with [3H]BP. These data suggest that TG can form an adduct with BPDE-I, as do other macromolecules (DNA, RNA, and protein). Therefore, a carcinogen-lipid adduct would be a useful biomarker for chemical carcinogenesis research and cancer risk assessment.

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Protective and Anti-Pathology Effects of Sm Fructose-1,6-Bisphosphate Aldolase-Based DNA Vaccine against Schistosoma mansoni by Changing Route of Injection

  • Saber, Mohamed;Diab, Tarek;Hammam, Olft;Karim, Amr;Medhat, Amina;Khela, Mamdouh;El-Dabaa, Ehab
    • Parasites, Hosts and Diseases
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    • 제51권2호
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    • pp.155-163
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    • 2013
  • This study aimed to evaluate the efficacy of fructose-1,6-bis phosphate aldolase (SMALDO) DNA vaccination against Schistosoma mansoni infection using different routes of injection. The SMALDO has been cloned into the eukaryotic expression vector pcDNA3.1/V5-His TOPO-TA and was used in injecting Swiss albino mice intramuscularly (IM), subcutaneously (SC), or intraperitoneally (IP) ($50{\mu}g/mouse$). Mice vaccinated with non-recombinant pcDNA3.1 served as controls. Each group was immunized 4 times at weeks 0, 2, 4, and 6. Two weeks after the last booster dose, all mice groups were infected with 80 S. mansoni cercariae via tail immersion. At week 8 post-infection, animals were sacrificed for assessment of parasitological and histopathological parameters. High anti-SMALDO IgG antibody titers were detected in sera of all vaccinated groups (P<0.01) compared to the control group. Both the IP and SC vaccination routes resulted in a significant reduction in worm burden (46.2% and 28.9%, respectively, P<0.01). This was accompanied by a significant reduction in hepatic and intestinal egg counts (41.7% and 40.2%, respectively, P<0.01) in the IP group only. The number of dead eggs was significantly increased in both IP and IM groups (P<0.01). IP vaccination recorded the highest significant reduction in granuloma number and diameter (54.7% and 29.2%, respectively, P<0.01) and significant increase in dead miracidia (P<0.01). In conclusion, changing the injection route of SMALDO DNA vaccination significantly influenced the efficacy of vaccination. SMALDO DNA vaccination via IP route could be a promising protective and antipathology vaccine candidate against S. mansoni infection.

Increased Prevalence of Chronic Disease in Back Pain Patients Living in Car-dependent Neighbourhoods in Canada: A Cross-sectional Analysis

  • Zeglinski-Spinney, Amy;Wai, Denise C.;Phan, Philippe;Tsai, Eve C.;Stratton, Alexandra;Kingwell, Stephen P.;Roffey, Darren M.;Wai, Eugene K.
    • Journal of Preventive Medicine and Public Health
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    • 제51권5호
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    • pp.227-233
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    • 2018
  • Objectives: Chronic diseases, including back pain, result in significant patient morbidity and societal burden. Overall improvement in physical fitness is recommended for prevention and treatment. Walking is a convenient modality for achieving initial gains. Our objective was to determine whether neighbourhood walkability, acting as a surrogate measure of physical fitness, was associated with the presence of chronic disease. Methods: We conducted a cross-sectional study of prospectively collected data from a prior randomized cohort study of 227 patients referred for tertiary assessment of chronic back pain in Ottawa, ON, Canada. The Charlson Comorbidity Index (CCI) was calculated from patient-completed questionnaires and medical record review. Using patients' postal codes, neighbourhood walkability was determined using the Walk Score, which awards points based on the distance to the closest amenities, yielding a score from 0 to 100 (0-50: car-dependent; 50-100: walkable). Results: Based on the Walk Score, 134 patients lived in car-dependent neighborhoods and 93 lived in walkable neighborhoods. A multivariate logistic regression model, adjusted for age, gender, rural postal code, body mass index, smoking, median household income, percent employment, pain, and disability, demonstrated an adjusted odds ratio of 2.75 (95% confidence interval, 1.16 to 6.53) times higher prevalence for having a chronic disease for patients living in a car-dependent neighborhood. There was also a significant dose-related association (p=0.01; Mantel-Haenszel chi-square=6.4) between living in car-dependent neighbourhoods and more severe CCI scores. Conclusions: Our findings suggest that advocating for improved neighbourhood planning to permit greater walkability may help offset the burden of chronic disease.

Resveratrol Exerts Differential Effects in Vitro and in Vivo against Ovarian Cancer Cells

  • Stakleff, Kimberly Sloan;Sloan, Tricia;Blanco, Denise;Marcanthony, Sharon;Booth, Tristan D.;Bishayee, Anupam
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권4호
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    • pp.1333-1340
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    • 2012
  • Epithelial ovarian cancer represents the most lethal gynecological cancer, and the high mortality rate makes this malignancy a major health concern. Poor prognosis results from an inability to detect ovarian cancers at an early, curable stage, as well as from the lack of an effective therapy. Thus, effective and novel strategies for prevention and treatment with non-toxic agents merit serious consideration. Resveratrol, obtained from grapes, berries, peanuts and red wine, has been shown to have a potent growth-inhibitory effect against various human cancer cells as well as in in vivo preclinical cancer models. The objective here was to evaluate potential antitumor effects of resveratrol in both in vitro and in vivo NuTu-19 ovarian cancer models. In vitro an invasion assay was performed. After 48 h, the numbers of viable cells that invaded the extracellular matrix layer were reduced by 94% with resveratrol in comparison to control. For the in vivo anti-tumor assessment, 10 rats were injected with NuTu-19 cells into the ovarian bursa. Thereafter, half were provided with a diet mixed with a dose of 100 mg resveratrol/kg body weight/day for 28 days. Following sacrifice, anticancer effects were assessed by histological evaluation of ovarian as well as surrounding tissues, and immunohistochemical detection of cell proliferation and apoptosis, but there were no observable differences between the control and resveratrol-treated groups for any of the biological endpoints. While resveratrol is effective in suppressing the in vitro cellular invasion of NuTu-19 ovarian cancer cells, these effects do not appear to impact on in vivo NuTu-19 ovarian cancers in rats.

Oxidative Stress-Induced Apoptosis in Chronic Myelogenous Leukemia K562 Cells by an Active Compound from the Dithio-Carbamate Family

  • Khoshtabiat, Laya;Mahdavi, Majid;Dehghan, Gholamreza;Rashidi, Mohammad Reza
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권9호
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    • pp.4267-4273
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    • 2016
  • Previous studies suggested that dithio-carbamates are potent apoptosis and anti-apoptosis inducing agents in various cancer cells. Here, the anti-proliferative and apoptosis inducing effects of a new derivative (2-NDC) from the dithio-carbamate family was examined in human leukemia K562 cells. We use thiazolyl blue tetrazolium bromide (MTT) to measure viability and cell growth inhibition. The 2-NDC showed effects on viability in a dose and time-dependent manner, inhibiting proliferation at concentrations of $10-30{\mu}M$ after 24-48 hours of treatment and increasing values after 72 hours at $40-120{\mu}M$. The cytotoxic effect of the compound was calculated with an $IC_{50}$ of $30{\mu}M$ after 24-hour. Apoptosis induction was confirmed by acridine orange-ethidium bromide (AO/EtBr) staining, DNA fragmentation assay, flow cytometric assessment and also caspase-3 activation assay. Furthermore, enzymes level such as superoxide dismutase (SOD) and catalase (CAT) involved in oxidative stress were evaluated. The results of this study demonstrated insignificant increase of intracellular ROS levels for 24 hours and reduction after 48-72 hours. In addition to reduction of intracellular thiol, caspase-3 like activity was also decreased in a time-dependent manner in cells treated with 2-NDC. Thus 2-NDC can be considered as a good candidate for further pharmaceutical evaluations.

In Vivo Effects of Lead on Erythrocytes Following Chronic Exposure through Drinking Water

  • Lee, Moo-Yeol;Shin, Jung-Hun;Han, Hee-Shim;Chung, Jin-Ho
    • Archives of Pharmacal Research
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    • 제29권12호
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    • pp.1158-1163
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    • 2006
  • More than 95% of lead, a environmental heavy metal, entering into blood accumulates in erythrocytes suggesting erythrocytes as an important target of lead toxicity. Recent studies reported that erythrocytes could contribute to blood coagulation via phosphatidylserine (PS) exposure in erythrocytes. However, in vivo effects of chronic lead exposure especially by drink-ing water on procoagulant activity of erythrocytes have not been studied yet. In the present study, we investigated the effects of chronic exposure of lead by drinking water on erythrocytes in rats. Groups of 40 male rats were provided with drinking water containing various concentrations of lead for 4 weeks and complete blood cell count, procoagulant activities of erythrocytes and platelets were evaluated with basic inspections on body weight and food/water consumption. The administration of lead containing drinking water increased the blood lead level (BLL) in a dose-dependent manner up to $22.39{\pm}2.26\;{\mu}g/dL$. Water consumption was significantly decreased while food consumption or body weight gain was not affected. In contrast to the previous findings with acute lead exposure, chronic lead exposure failed to increase PS exposure in erythrocytes with statistical significance although some trends of enhancement were observed. It implies that a certain adaptation might have happened in body during repeated exposure to lead, resulting in attenuation of PS exposure. With this study, we believe that a valuable information was provided for the study on the toxicological significance and the risk assessment of lead contaminated drinking water.

Responses of Various Biomarkers in Common Carp (Cyprinus carpio) Exposed to Benzo[k]fluoranthene

  • Kim, Woo-Keun;Kim, Ja-Hyun;Yeom, Dong-Hyuk;Lee, Sung-Kyu
    • 생태와환경
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    • 제41권3호
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    • pp.331-337
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    • 2008
  • Polycyclic aromatic hydrocarbons (PAHs) derived from leakage of fossil fuels and incomplete combustion of organic materials have been considered as harmful contaminants in environments. This study evaluated the effect of benzo[k]fluoranthene (BkF), one of the PAHs, using the multiple biomarkers and applied the integration model with those biomarker responses. After 10 days of the exposure at the measured concentrations of BkF (6, 25, and 45 ${\mu}g\;L^{-1}$), the changes of the four biomarkers, that is, 7-ethoxyresorufin-O-deethylase (EROD), DNA single-strand breaks (Comet), acetylcholinesterase (AChE) and vitellogenin (VTG) in the common carp (Cyprinus carpio) were observed. The standardized values of four biomarker responses were computed and integrated as star plots, representing Integrated Biomarker Respnse (IBR) values. DNA damage was induced in a dose-dependent manner, and increased significantly compared with that in the control. EROD and VTG levels were significantly elevated at low concentrations of BkF. On the other hand, AChE activities were not altered by BkF. IBR values increased as the exposure concentrations increased. Thus, the metabolic, endocrine and genetic changes of the biomarker responses in the common carp exposed to BkF should be considered in the case of the ecological risk assessment of the BkF in fish and it can be used as a biomonitoring tool in aquatic ecosystems. In addition, star plots can be used as a useful analysis tool in multibiomarker integration approach.