• 제목/요약/키워드: Dose-response relationship

검색결과 241건 처리시간 0.031초

방사선에 전신 조사된 마우스 음와 세포의 아포토시스 유도를 이용한 생물학적 선량 측정 모델 개발 연구 (Mouse model system based on apoptosis induction to crypt cells after exposure to ionizing radiation)

  • 김태환
    • 대한수의학회지
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    • 제41권4호
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    • pp.571-578
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    • 2001
  • 방사선 피폭선량의 예측을 위한 방사선 민감 지표 모델 개발의 일환으로 apoptotic fragment assay법이 방사선에 피폭된 후 체내 피폭선량을 예측할 수 있는 지표로의 이용 가능성을 평가하기 위하여 코발트-60 감마선과 의료용 싸이크로트론 50MeV($p{\rightarrow}Be^+$) fast neutron 을 0.25Gy에서 1Gy의 선량을 마우스에 각각 전신 조사한 후 소장 음와세포내 apoptotic crypt cell의 수적 변화를 관찰하였다. 저선량 조사군에서 apoptotic crypt cell의 출현 빈도가 1Gy까지 급격하게 증가한 것으로 보아 방사선이 stem cell 지역에 있는 crypt cell의 형태학적 변화를 유발하는 것으로 나타났다. 이상의 결과는 아포토시스가 손상된 세포를 제거하므로 손상된 방사선 민감 표적 장기의 항상성 유지에 중요한 역할을 하는 것으로 판단되었다. Apoptotic fragments의 발생빈도에 대한 선량-반응 곡선에 있어서 음와세포는 중성자조사군이 $y=0.18+(9.728{\pm}0.887)D+(-4.727{\pm}1.033)D^2$ ($r^2=0.984$)으로, 반면에 감마선조사군은 $y=0.18+(5.125{\pm}0.601)D+(-2.652{\pm}0.7000)D^2$ ($r^2=0.970$)의 식을 얻었다. 이와 같이 중성자조사군과 감마선조사군은 공히 linear quadratic model 로 관찰되었다. apoptotic fragments 의 발생빈도와 조사 선량간에 유의한 효과가 있는 것으로 확인되었다. 이상의 결과에서 조사선량의 증가에 비례하여 방사선 민감 세포의apoptotic fragments 가 수적으로 증가하였으며, 고준위 방사선과 저준위 방사선은 선량 반응 관계식과 시간 경과에 따른 영향이 매우 유사하였으며, 마우스 음와세포의 apoptosis 유도에 대한 중성자선의 방사선 생물학적 효과비(RBE)는 2.072이였다. 그리고 모든 방사선조사군에서 방사선피폭 후 4시간과 6시간에 apoptosis 유도가 가장 많았으며, 음와세포의 형태학적 소견은 정상 대조군에서 관찰되지 않는 전형적인 apoptotic fragments 가 나타났다. 따라서 음와 세포에서의 아포토시스 유도는 방사선 피폭으로 발생된 세포 손상의 생물학적 영향 평가검색, 방사선 방호제의 민감도 검사, 방사성 동위원소의 체내 오염에 대한 체내 피폭선량 예측의 지표 및 방사선 민감 표적장기의 손상정도 파악에 이용 가능할 것임. Apoptotic fragment assay 법은 0.25Gy에서 1Gy 까지의 선량에서 간편하고 빠르며 재현성이 있는 지표로서 방사선 민감 표적 장기의 선량 반응 평가와 방사선 피폭후 조기 피폭선량 예측을 위한 방사선 생물학적 선량측정법의 좋은 지표로 사용할 수 있을 것으로 사료됨.

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서양의학 독성학의 기본적 개념 및 한약의 $LD_{50}$ (Basic Concepts of Western Medicine Toxicology and $LD_{50}$ in Herbal Drugs)

  • 박영철;이선동;박경식
    • 대한예방한의학회지
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    • 제3권2호
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    • pp.91-100
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    • 1999
  • Today, toxicology is used for many purpose, in many fields. Classification of special toxic effect is related next 4 important principles. 1. The chemical substance must move to target organ or tissue that can induce Biological effect. For this movement, we have to understand the physical-chemical characteristic of substance, and the rout of absorption, metabolism, diffusion and excretion of toxic substance. 2. Every biological effect that induced by chemical substance is not harmful. For example, some specific chemical substance is not harmful in liver enzyme system. 3. The strength of biological effect induced by chemical substance is deep related with dose. Nearly all substance is not effective below the specific dose, and it may toxic to death over the specific dose. It is the 'Dose - response relationship' But carcinogen may toxic whether it is law dose or not. 4. The information that was obtained by experimental animal test, could have to adapt in human biology. Because biological effect of chemical substance could be different in every biological species. In past, drugs was obtained by animal or plants. But in the future, it could be obtained by biochemistry, and genome project. Therefore, in Oriental medicine, research and approach is needed at this time, and have to develop new method of experience in toxic method.

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정신분열증 환자에서의 Haloperidol 및 Reduced Haloperidol의 혈장농도와 임상반응과의 상관성 (Relationship between Plasma Concentrations of Haloperidol and Its Metabolite, Reduced Haloperidol, and Clinical Response in Schizophrenia)

  • 박경호;김무진;이명걸;심창구;이민화
    • Journal of Pharmaceutical Investigation
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    • 제23권3호
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    • pp.165-177
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    • 1993
  • The relationship between the plasma haloperidol (HP) concentration and clinical response, and the effects of its active metabolite, reduced haloperidol (RH) on clinical response of HP were investigated in schizophrenic patients. In clinical study I, with 17 schizophrenic patients (male 8, fermale 9) who were administered with three different fixed doses of HP (15, 30 and 50 mg/day) for 3 weeks, the concentrations of HP and RH in plasma and blood and clinical response had been checked before and every week during the study. The clinical response was evaluated by the method of brief psychiatric rating scale (BPRS), and relative improvement of clinical response based on baseline BPRS (before drug treatment) was calculated. The concentrations of HP and RH in plasma and blood were assayed by HPLC. In clinical study II, the plasma RH/HP concentration ratios were checked in 11 patients who were administered with high doses of HP, over 60 mg a day, because of the poor clinical response at usual doses of HP. Plasma HP concentration and relative improvement of BPRS at 3 week in schizophrenic patients showed a 'curvilinear' relationship, and the clinical response was improved relatively over 50% based on the baseline BPRS in the range of $5{\sim}57\;ng/ml $ of HP in plasma. Also, the plasma RH concentrations were increased nonlinearly as the plasma HP concentration increased, and in high plasma HP concentration, over 30 ng/mI, clinical response gradually decreased, while the plasma RH/HP concentration ratio increased nonlinearly. Blood partition coefficients of HP and RH were not changed according to daily HP dose and duration of drug therapy. From these results, it is noted that the higher plasma RH/HP concentration ratio, resulted from the accumulation of RH as HP concentration increased, might explain the 'curvilinear' decrease of HP clinical response.

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조류인플루엔자 바이러스의 양-반응 모형 (Dose-Response Relationship of Avian Influenza Virus Based on Feeding Trials in Humans and Chickens)

  • 박선일;이제용;전종민
    • 한국임상수의학회지
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    • 제28권1호
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    • pp.101-107
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    • 2011
  • This study aimed to determine dose-response (DR) curve of avian influenza (AI) virus to predict the probability of illness or adverse health effects that may result from exposure to a pathogenic microorganism in a quantitative microbial risk assessment. To determine the parametric DR relationship of several strains of AI virus, 7 feeding trial data sets challenging humans (5 sets) and chickens (2 sets) for strains of H3N2 (4 sets), H5N1 (2 sets) and H1N1 (1 set) from the published literatures. Except for one data set (study with intra-tracheal inoculation for data set no. 6), all were obtained from the studies with intranasal inoculation. The data were analyzed using three types of DR model as the basis of heterogeneity in infectivity of AI strains in humans and chickens: exponential, beta-binomial and beta-Poisson. We fitted to the data using maximum likelihood estimation to get the parameter estimates of each model. The alpha and beta values of the beta-Poisson DR model ranged 0.06-0.19 and 1.7-48.8, respectively for H3N2 strain. Corresponding values for H5N1 ranged 0.464-0.563 and 97.3-99.4, respectively. For H1N1 the parameter values were 0.103 and 12.7, respectively. Using the exponential model, r (infectivity parameter) ranged from $1.6{\times}10^{-8}$ to $1.2{\times}10^{-5}$ for H3N2 and from $7.5{\times}10^{-3}$ to $4.0{\times}10^{-2}$ for H5N1, while the value was $1.6{\times}10^{-8}$ for H1N1. The beta-Poisson DR model provided the best fit to five of 7 data sets tested, and the estimated parameter values in betabinomial model were very close to those of beta-Poisson. Our study indicated that beta-binomial or beta-Poisson model could be the choice for DR modeling of AI, even though DR relationship varied depending on the virus strains studied, as indicated in prior studies. Further DR modeling should be conducted to quantify the differences among AI virus strains.

Vegetable Oil Intake and Breast Cancer Risk: a Meta-analysis

  • Xin, Yue;Li, Xiao-Yu;Sun, Shi-Ran;Wang, Li-Xia;Huang, Tao
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권12호
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    • pp.5125-5135
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    • 2015
  • Background: Total fat intake may be associated with increased risk of breast cancer, and fish oil has been suggested as a protection factor to breast cancer. But the effect of vegetable oils is inconclusive. We aimed to investigate the association with high vegetable oils consumption and breast cancer risk, and evaluated their dose-response relationship. Design: We systematically searched the MEDLINE, EMBASE, Cochrane databases, and CNKI updated to December 2014, and identified all observational studies providing quantitative estimates between breast cancer risk and different vegetable oils consumption. Fixed or random effect models were used to estimate summary odds ratios for the highest vs. lowest intake, and dose-response relationship was assessed by restricted cubic spline model and generalized least-squares trend (GLST) model. Results: Five prospective cohort studies and 11 retrospective case-control studies, involving 11,161 breast cancer events from more than 150,000 females, met the inclusion criteria. Compared with the lowest vegetable oils consumption, higher intake didn't increased the risk of breast cancer with pooled OR of 0.88 (95% CIs:0.77-1.01), and the result from dose-response analyses didn't show a significant positive or negative trend on the breast cancer risk for each 10g vegetable oil/day increment (OR=0.98, 95% CIs: 0.95-1.01). In the subgroup analyses, the oils might impact on females with different strata of BMI. Higher olive oil intake showed a protective effect against breast cancer with OR of 0.74 (95% CIs: 0.60-0.92), which was not significant among the three cohort studies. Conclusions: This meta-analyses suggested that higher intake of vegetable oils is not associated with the higher risk of breast cancer. Olive oil might be a protective factor for the cancer occurrence among case-control studies and from the whole. Recall bias and imbalance in study location and vegetable oils subtypes shouldn't be ignored. More prospective cohort studies are required to confirm the interaction of the impact of vegetable oils on different population and various cancer characteristic, and further investigate the relationship between different subtype oils and breast cancer.

Ultraviolet Radiation-Induced Apoptosis is Inversely Correlated with the Expression Level of Poly(ADP-ribose) Polymerase

  • Oh, Kyu Seon;Lee, Dong Wook;Chang, Jeong Hyun;Moon, Yong Suk;Um, Kyung ll
    • Animal cells and systems
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    • 제5권1호
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    • pp.77-83
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    • 2001
  • The present study was conducted to elucidate whether the expression level of poly(ADP-ribose) polymerase (PARP) is related to the ultraviolet radiation (UV)-induced apoptosis. After treatment of the mammalian cell lines HeLa S3 and Chinese hamster ovary (CHO) with 50 J/m2 UV, induction of apoptosis was determined by several means during 24 h post-incubation. Incidence of apoptosis was much lower in CHO than HeLa S3 cells based on the percentage of apoptotic cells in terms of morphological changes in nucleus or direct counting of viable cells and qualitative or quantitative DNA fragmentation. Interestingly, when the expression level of PARP was measured by western blotting, the amounts of PARP that was retained at each time point inversely correlated with the incidences of apoptosis in these cells. Concomitant with generation of the 85 kDa fragment, 116 kDa PARP disappeared in HeLa S3 within 6 h after UV treatment, whereas a fair amounts of 116 kDa band was still retained in CHO cells at 36 h post-incubation. This inverse relationship was also observed in the adaptive response system, in which cells weve treated with a high dose of UV after pretreatment with a low dose. As expected, typical adaptive responses appeared in CHO cells but not in HeLa cells, showing greater cell viability and lesser DNA fragmentation. During the adaptive response in CHO cells, PARP was expressed at much higher level compared to the single, high dose-treated cells. Interestingly, even though PARP was induced at 6 h post-incubation In both cell types, its expression was more prominent in CHO cells. Thus, our data indicate that the retained level of intact PARP against UV damage inversely correlates with incidence of apoptosis in mammalian cells, and also suggest that a machinery to protect the PARP degradation against UV damage exists in CHO but not in HeLa S3 cells.

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Lymphoblastosis Inhibition and Plaque-forming Cell Response of Several Anti-inflammatory Steroids in Mice

  • Choi, Hong-Pil;Kim, Kilhyoun;Kim, Hyun-Pyo
    • Archives of Pharmacal Research
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    • 제15권2호
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    • pp.169-175
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    • 1992
  • Anti-inflammatory glucocorticoid (GC) derivatives have been clinically used in immune-malfunctional diseases for their immunosuppressive activity. However, there is still a lack of knowledge on the relationship between anti-inflammatory and immunosuppressive activities. In order to compare immunosuppressive activities with the known anti-inflammatory activities of the GC derivatives, eight clinically used GC derivatives including hydrocortisone, prednislone, 6$\alpha$-methyl prednisolone, triamcinolone, dexamethasone, betamethasone, triamcinolone acetonide and fluocinolone acetonide were selected, and lymphoblastosis inhibition and plaque-forming cell (PFC) response in mice were studied as immunological parameters. In Con A-induced lymphoblatosis inhibition invitro, all derivatives showed potent inhibition $IC_{50}$ values of the derivaties except methyl prednisolone and triamcinolone were less than $10^{-7}$M and good dose dependency was obtained. This result was well correlated with that of their anti-inflammatory potencies obtained. This result was well correlated with that of their anti-inflammatory potencies and their receptor binding affinities. However, in PFC response, consistent result were not obtained. Total numbers of PFCs per spleen were decreased by some derivatives, but numbers of PFCs per $10^6$ cells were not decreased by systemic administration of but numbers of PFCs per $10^6$ cells were not decreased by systemic administration of GC at the dose of 0.05 mg/mouse. Furthermore, at the dose of 0.1 mg/mouse, numbers of PFCs per $10^6$ cells were found to be increased, although total PFCs per spleen were decreased.

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외부 공간에서 복합소음에 대한 불쾌감 연구 (Dose-response relationship for annoyance caused by combined noise sources in urban spaces)

  • 이평직;유진;정충일;연준오;전진용
    • 한국소음진동공학회:학술대회논문집
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    • 한국소음진동공학회 2008년도 춘계학술대회논문집
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    • pp.264-267
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    • 2008
  • Relationship between exposure to combined noise sources and community annoyance have been investigated. Social surveys were conducted in urban spaces near the construction site with road traffics. The question relating to noise annoyance was answered on an 11-point numerical scale and 5-point verbal scale according to ISO 15666. The questionnaire also contained demographic factors, interference with daily activities, health-related symptoms, and noise sensitivity. Noise levels were measured in terms of A-weighted equivalent level ($L_{Aeq}$), and noise mapping technique was applied to predict the noise levels of urban spaces. Synthesis curves for the relationship between noise levels and percentage highly annoyed for combined noise sources were derived, and compared to the curves from a single noise source.

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THI를 이용한 항공기소음이 주민 건강상태에 미치는 영향 (Questionnaire study conducted around Gimpo International Airport by using THI)

  • 손진희;이건;장서일
    • 한국소음진동공학회:학술대회논문집
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    • 한국소음진동공학회 2007년도 추계학술대회논문집
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    • pp.436-441
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    • 2007
  • This study was carried out to evaluate health effects of aircraft noise using THI(Todai Health Index). The questionnaire survey was conducted around the Gimpo International Airport in Seoul, Korea from 8 August to 9 September. Study subjects, 614 residents, were divided into three groups following to the aircraft noise level: under 75WECPNL(area(1)), $75{\sim}80$WECPNL(area(2)) and $80{\sim}85$WECPNL(area (3)). Twelve scale scores are converted to dichotomous variables based on scale scores of 90 percentile value or 10 percentile value in the control group. Logistic regression analysis taking twelve scores converted as the dependent variables and WECPNL(area), age, gender as the independent variables is conducted. Significant dose-response relationships are found in the scale of MOUT, DEPR, NERV, LIFE, where p denotes significance probability of trend test. Factor analysis was carried out and 2 factors are extracted which may be called "somatic factor" and "mental factor". The dose-response relationship with these factors and noise exposure is not clear. But strangely the odds ratio of mental factor in area 2 is the highest and the annoyance of this area is also higher than other areas.

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혈당측정을 위한 폴리우레탄 진단막의 제조(6) : 헤마토크릿이 글루코우즈의 농도 측정에 미치는 영향 (Preparation of Polyurethane Diagnostic Membranes for Blood Glucose Measurements (6) : Effects of Hematocrit on Measurements of Glucose Concentration)

  • 권석기
    • 멤브레인
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    • 제20권3호
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    • pp.197-202
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    • 2010
  • 당뇨병 환자의 혈당치 측정을 위하여 폴리우레탄으로 만들어진 진단막을 제조하였다. 혈액 속의 글루코우즈의 농도를 변화시켜가며 폴리우레탄 진단막을 가지고 680 nm에서의 최종흡광도를 측정하였다. 시간에 따른 흡광도 변화량(K/S)의 최종 결과치가 글루코우즈의 농도가 증가함에 따라 직선적으로 증가하였다. 헤마토크릿이 글루코우즈의 농도 측정에 미치는 영향을 조사하였다. 낮은 헤마토크릿에서는 글루코우즈의 농도와 K/S와의 기울기 값(Dose-Response Slope : DRS)이 플라즈마와 비교해 큰 차이를 보이지 않았다. 그러나 높은 헤마토크릿(40% 이상)에서는 상당히 감소함을 알 수 있었다.