• Title/Summary/Keyword: dose-effect relationship

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Pharmacodynamic Modeling of Vincristine in Lymphoma Patients (림프종 환자에서 회귀모형을 이용한 vincristine의 약물 용량 예측 인자 및 부작용 모델 연구)

  • Seo, Jeong-Won;Kim, Dong-Hyun;Yun, Jin-Sang;Kim, Seon-Hwa;Choi, Bo-Yoon;Oh, Jung-Mi;Kwon, Kwang-Il
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.2
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    • pp.145-155
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    • 2011
  • The objective of this study was to determine whether any pretreatment parameters were associated with pharmacological effect or toxicity parameters after vincristine administration and to describe a mathematical model, which explains the interpatient pharmacodynamic variability. The relationship between patient characteristics and vincristine dose and hematological toxicity were evaluated. 68 pediatric and adolescence patients and 107 adults with acute lymphoblastic leukemia were treated with vincristine $1.5mg/m^2/day$ IV and other anticancer drugs as scheduled. Complete blood counts and other blood test results were obtained. The input variables were age, gender, weight, lean body weight (LBW), height, body surface area, vincristine dose and total vincristine dose. The outcome measures were nadir values (white blood cells, absolute neutrophil counts, hemoglobin, and platelets); the absolute decrease, relative decrease, and survival fraction of blood cells. Polynomial regression analysis was carried out to determine the other significant covariates. The variability of $WBC_{nadir}$ was modeled with good precision and accuracy with a two-covariate model. This model should be validated and improved on with further clinical data. We believe that such pharmacodynamic modeling should be explored further to determine its performance and clinical relevance compared with modeling using pharmacokinetic parameter.

Effect of Electron Beam Irradiation on the Properties of Softwood Unbleached Kraft Pulp (전자선 전처리에 따른 침엽수 미표백 크라프트 펄프의 특성평가)

  • Kim, Eun Hea;Lee, Ji Young;Jeun, Joon Pyo;Kim, Sun Young;Kim, Chul Hwan;Park, Jong Hye
    • Journal of Korea Technical Association of The Pulp and Paper Industry
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    • v.47 no.5
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    • pp.68-73
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    • 2015
  • Electron beam irradiation is also an eco-friendly treatment compared to other physical and chemical treatments. In this study, we attempted to evaluate the possibilities of energy savings by applying electron beam irradiation to the refining process. After softwood unbleached kraft pulp (UKP) was irradiated with electron beams at 50 and 100 kGy, it was beaten in a laboratory beater, and then its freeness and fiber properties were analyzed. The physical properties of their fiber handsheet were also and measured. As the irradiation dose of the electron beam and the beating time increased, lower freeness and fiber lengths of the UKP were observed. Handsheets made from UKP that was irradiated by electron beam and beaten showed a reciprocal relationship with the irradiation dose of the electron beam, in particular, the strength of the handsheets decreased dramatically at 100 kGy of irradiation. Therefore, it was confirmed that electron beam irradiation is effective in reducing the beating time or beating energy. But the irradiation dose must be controlled under 50 kGy to minimize the loss of paper strength.

Metal Concentrations in Rats and Fetuses Treated by Herbal Decoction, Samultang (사물탕투여가 임신랫드의 모체 및 태자에 미치는 영향 -유해금속(As, Cd, Pb, Hg)과 양-반응관계를 중심으로-)

  • Shin, Heon-Tae;Park, Hae-Mo;Lee, Sun-Dong
    • Journal of Society of Preventive Korean Medicine
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    • v.13 no.2
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    • pp.77-87
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    • 2009
  • Purpose : To evaluate the effects of Samultang(SMT) on the metals in the dams and fetuses Method : SMT(Decoction) was administered orally using different concentrations to pregnant Sprague-Dawley rats for 20days after being assigned randomly to 5 groups. Each group has 11 dams. Pregnant rats were sacrificed at the 20th day of gestation and metal concentration in the dams and fetuses was observed using a ICP-MS and mercury analyzer. Results : Hg concentration in the blood of dams was lower in the $SMT{\times}1$, $SMT{\times}2$, $SMT{\times}4$group than VC(Vehicle Control) and Control group. Hg concentration in the organs of dams was lower in the $SMT{\times}1$, $SMT{\times}2$, $SMT{\times}4$ group than VC, Control group. Whereas Cd concentration in the organs of fetuses was getting lower as increasing SMT dose, Hg concentration in the organs of fetuses was getting higher as increasing SMT dose. Discussion and Conclusion : There were not any significant harmful differences of metal concentration in the dams and fetuses treated by SMT. Particularly, SMT showed the possibility of efficacy to reduce the concentration of Hg in dams but to increase the concentration of Hg in fetuses. The mechanism of reduction is not yet proven. A hypothesis says there is a possibility of the chelation effect between the essential elements of herbs and heavy metals. Another hypothesis is the possibility of Hg transmission from dam to fetus. Further study should be conducted to make guidelines for the safe use of herbal medicine.

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Low-Dose Bisphenol A Increases Bile Duct Proliferation in Juvenile Rats: A Possible Evidence for Risk of Liver Cancer in the Exposed Population?

  • Jeong, Ji Seong;Nam, Ki Taek;Lee, Buhyun;Pamungkas, Aryo Dimas;Song, Daeun;Kim, Minjeong;Yu, Wook-Joon;Lee, Jinsoo;Jee, Sunha;Park, Youngja H.;Lim, Kyung-Min
    • Biomolecules & Therapeutics
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    • v.25 no.5
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    • pp.545-552
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    • 2017
  • Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett's test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in $C_{max}$, and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in $C_{max}$ and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.

Chromosome Aberrations and Sister Chromatid Exchanges of Hospital Workers Exposed to Radiation (방사선취급 병원근무자들의 염색체이상 및 자매염색분체교환 빈도)

  • Cha, Ae-Ri;Kim, Mi-Sun;Hwang, In-Kyung;Lee, Su-Ill;Cho, Byung-Mann;Kim, Don-Kyoun
    • Journal of Preventive Medicine and Public Health
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    • v.31 no.4 s.63
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    • pp.616-627
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    • 1998
  • In order to evaluate the cytogenetic hazard among hospital workers potentially exposed to low dose of radiation, the analysis of chromosome aberrations(CA) and sister chromatid exchanges(SCE) in lymphocytes were performed in 79 hospital workers and 79 non-exposed workers. The mean frequency of chromosomal exchange and deletion(respectively, $0.20\times10^{-2}/cell\;and\;0.39\times10^{-2}/cell$) in the exposed group were significantly higher than those$(0.07\times10^{-2}/cell\;and\;0.23\times10^{-2}/cell)$ in control group. The frequency of sister chromatid exchanges was 5.04/cell in the control vs. 6.57/cell in the exposed group. There were also significant differences in the mean frequencies of CA and SCE adjusted for age, sex, smoking, drinking between two groups. There were no evidence of significant increase of CA and SCE according to the department or duration of employment. But the frequency of cells having chromosome aberration was significantly higher in the exposed group than in the control group related to duration of employment. There was no dose-effect relationship between the cumulative doses and the frequency of CA and SCE. But in the case of last 1 yr cumulative dose, there were evidence of significant dose-dependant increase of chromosome type CA and percentage of cells with aberration. The result suggest that there is cytogenetic hazard in risk group like hospital workers handling low dose radiation. And the analysis CA and SCE are useful biological indicators for the exposure of low dose level of radiation.

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Studies on the mechanism of cytotoxicities of polyacetylenes against L1210 cell

  • Kim, Young-Sook;Jim, Seung-Ha;Kim, Shin-Il;Hahn, Dug-Ryong
    • Archives of Pharmacal Research
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    • v.12 no.3
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    • pp.207-213
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    • 1989
  • This study was performed to investigate the mechanism of in vitro cytotosic actions of polyacetylenes which are panaxydol, panaxynol and panaxytriol isolated from Panax ginseng C. A. Meyer. DNA synthesis of L1210 cells was significantly inhibited with dose dependent pattern when L1210 cells were treated for 1 hour with over 5 .mu.g/ml of polyacetylenes. Panaxydol which had the most potent cytotoxicity among three polyacetylenes showed also the strongest inhibitory effect on DNA synthesis. Intracellular cyclic AMP levels of L1210 cells treated with 2.5 $\mu$g/ml of panaxydol or panaxytriol were significantly elevated on the incubation duration. The elevation of cyclic AMP levels by panaxytriol was higher than that by panaxydol, but no significant increase in cyclic AMP by panaxynol was observed. All three polyacetylenes had no effect on glycolysis of L1210 cells. Electron microscopic observations revealed that polyacetylenes caused damage to plasma membranes of L1210 cells in proportion to their cytotoxicities at each $ED_{50}$ value (panaxydol > panaxynol> panaxytriol). These results suggest that cytotoxicities of polyacetylenes against L1210 cells might be mediated by elevated cyclic AMP level, even though the relationship among their cytotoxicities, inhibitory effect on DNA synthesis and ability to elevation of cyclic AMP level are not fully agreed, and might be also related to membrane damage.

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The apoptotic fragment assay in rat peripheral lymphocytes and crypt cells with whole body irradiation with 60Co ϒ-rays and 50 MeV cyclotron fast neutrons (코발트-60 감마선과 50 MeV 싸이크로트론 고속 중성자선에 전신조사된 랫드의 말초 임파구와 음와 세포의 아포토시스 유도를 이용한 생물학적 선량 측정 모델 개발 연구)

  • Kim, Tae-hwan
    • Korean Journal of Veterinary Research
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    • v.41 no.2
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    • pp.203-210
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    • 2001
  • Here, we compared the effectiveness of 50 MeV($p{\to}RBe^+$) cyclotron fast neutrons versus $^{60}Co$ ${\gamma}$-rays by the apoptotic fragment frequency in both rat peripheral lymphocytes and crypt cells to check a radiobiological endpoint. The incidence of apoptotic cell death was increased in all irradiated groups, and radiation at all doses trigger rapid changes in both crypt cells and peripheral lymphocytes. These data suggest that apoptosis may play an important role in homeostasis of damaged radiosensitive target organ by removing damaged cells. The curve of dose-effect relationship for these data of apoptotic fragments frequencies was $y=0.3+(6.512{\pm}0.279)D(r^2=0.975)$ after neutrons, while $y=0.3+(4.435{\pm}0.473)D+(-1.300{\pm}0.551)D^2(r^2=0.988)$ after ${\gamma}$-rays. In addition, $y=3.5+(118.410{\pm}10.325)D+(-33.548{\pm}12.023)D^2(r^2=0.992)$ after ${\gamma}$-rays in rat lymphocytes. A significant dose-response relationship was found between the frequency of apoptotic cell and dose. These data show a trend towards increase of the numbers of apoptotic cells with increasing dose. Dose-response curves for high and low linear energy transfer (LET) radiation modalities in these studies were different. The relative biological effectiveness (RBE) value for crypt cells was 1.919. In addition, there were significant peaks on apoptosis induction at 4 and 6h after irradiation, and the morphological findings of the irradiated groups were typical apoptotic fragments in crypt cells that were hardly observed in the control group. Thus, apoptosis induction in both crypt cells and peripheral lymphocytes could be a useful endpoint of rat model for studying screening test and microdosimetic indicator to evaluate the biological effects of radiation-induced cell damage.

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Evaluation of DNA Double Strand Breaks in Human and Mouse Lymphocyte Following ${\gamma}-Irradiation$ (${\gamma}-Ray$ 조사에 따른 사람의 정상임파구와 마우스 정상임파구의 DNA Double Strand Break 발생율에 대한 비교분석)

  • Kim Tae Hwan;Kim Sung Ho;Chung In Yong;Cho Chul Koo;Ko Kyung Hwan;Yoo Seong Yul
    • Radiation Oncology Journal
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    • v.11 no.2
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    • pp.219-225
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    • 1993
  • The evaluation of radiation-induced DNA double strand breaks (DSB) was made following irradiation of human lymphocytes, murine lymphocytes and EL-4 leukemia cells over a wide dose range of $^{60}Co\;{gamma}-rays.$ In lipopolysaccharide (LPS) or phytohemagglutinin (PHA)-stimulated murine lymphocytes, the slopes of the stand scission factor (SSF) revealed that lymphocytes with LPS increased DNA DSB formation by a factor of 1.432 (p<0.005). Furthermore, strand break production was relatively inefficient in the T lymphocytes compared to the B lymuhocytes. And EL-4 leukemia cells were found to form significantly more DNA DSB to a greater extent than normal lymphocytes (p<0.005). The in vitro studies of the intrinsic radiosensitivity between human lymphocytes and murine lymphocytes showed similar phasic kinetics. However, murine lymphocytes were lower in DNA DSB formation and higher in the relative radiation dose of 10 percent DNA strand breaks at 3.5 hours following ${gamma}-irradiation$ than human lymphocytes. Though it is difficult to interpret these results, these differences may be result from environmental and genetic factors. From our data, if complementary explanations for this difference will be proposed, the differences in the dose-effect relationship for the induction of DSB between humans and mice must be related to interspecies variations in the physiological condition of the peripheral blood in vitro and not to differences in the intrinsic radiation sensitivity of the lymphocytes. These results can be estimated on the basis of dose-effect correlation enabling the interpretation of clinical response and the radiobiological parameters of cytometrical assessment.

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A Monte Carlo Study of Secondary Electron Production from Gold Nanoparticle in Kilovoltage and Megavoltage X-rays (몬테칼로 기법을 이용한 금 나노입자에서의 2차 전자 발생 평가)

  • Hwang, Chul-Hwan;Kang, Se-Sik;Kim, Jung-Hoon
    • Journal of the Korean Society of Radiology
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    • v.10 no.3
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    • pp.153-159
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    • 2016
  • This study investigated relationship between secondary electrons produced from single gold nanoparticle as a result of its interaction with radiation and particle size and incidence energy, provided basic data related to the dose enhancement effect based on gold nanoparticles. Monte Carlo simulation was applied by using MCNPX MC code, 50, 100, 150 kV and 6, 15 MV x-ray energy was used. In a water phantom, single gold nanoparticles that are 30, 50, 70, 90, and 110 nm in diameter were placed and the tally volume was designated at every 10 nm. Difference in electrons produced from gold nanoparticles was normalized based on absence of nanoparticle. When the X ray energy decreased and the diameter of gold particles increased, more electrons were produced. When the energy was lower, in the linear formula related to nanoparticle size and electron production, the gradient was higher. And, in comparison to the MV X-ray, at kV X-ray, significantly more electrons were produced. This study can be used as data to understand the dose enhancement effect based on gold nanoparticles, and further research related to various materials that dose enhancement including gold nanoparticles needs to be conducted.

The Effect of Steroid Therapy for Idiopathic Unilateral Vocal Cord Palsy (특발성 일측성 성대마비에서 경구 스테로이드 요법의 효과)

  • Bae, Jong-Won;Lee, GilJoon
    • Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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    • v.30 no.2
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    • pp.107-111
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    • 2019
  • Background and Objectives Idiopathic unilateral vocal fold paralysis (IVFP) is believed to be due to inflammation and edema of the recurrent laryngeal nerve caused by viral diseases such as upper respiratory tract infections. Corticosteroid has a potent anti-inflammatory action which should minimize nerve damage. The purpose of this study was to investigate the effect of oral steroid therapy on IVFP. Materials and Method Study was performed for the IVFP patient from January 2012 to August 2017. Patient's dermography, direction and location of paralyzed vocal cords, history of hypertension, diabetes, cerebrovascular disease, and other underlying disease, smoking history, alcohol consumption and upper respiratory tract infection, and symptoms were investigated. Treatment was divided into three groups: the observation group, low-dose group, and high-dose group, and the recovery rate and time of vocal cord paralysis were analyzed in each group. Results Thirty-seven patients were enrolled in this study. There was no relationship between oral steroid use, dosage and recovery of vocal cord paralysis. Oral steroids showed a rapid recovery of vocal cord paralysis, but there was no statistically significant difference in the time of recovery of vocal palsy with or without steroids (p=0.673). In addition, there was no statistically significant difference in recovery rate between the period to start of treatment, presence of diabetes mellitus, and treatment modality, but the recovery rate was high in the group with upper respiratory tract infection history (p=0.041). Conclusion In IVFP, oral steroid therapy has no significant difference in time and extent of recovery compared to the case of spontaneous recovery.