• Korean Journal of Veterinary Research
• /
• v.41 no.4
• /
• pp.571-578
• /
• 2001

To evaluate if the apoptotic fragment assay could be used to estimate the dose prediction after radiation exposure, we examined apoptotic mouse crypt cells per 1,000 cells after whole body $^{60}Co$ $\gamma$-rays and 50MeV ($p{\rightarrow}Be^+$) cyclotron fast neutron irradiation in the range of 0.25 to 1 Gy, respectively. The incidence of apoptotic cell death rose steeply at very low doses up to 1 Gy, and radiation at all doses tigger rapid changes in crypt cells in stem cell region. 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 the data of apoptotic fragments was obtained by the linear-quadratic model $y=0.18+(9.728{\pm}0.887)D+(-4.727{\pm}1.033)D^2$ ($r^2=0.984$) after $\gamma$-rays irradiation, while $y=0.18+(5.125{\pm}0.601)D+(-2.652{\pm}0.7000)D^2$ ($r^2=0.970$) after neutrons in mice. The dose-response curves were linear-quadratic, and 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 crypt cells with increasing dose. Both the time course and the radiation dose-response curve for high and low linear energy transfer (LET) radiation modalities were similar. The relative biological effectiveness (RBE) value for crypt cells was 2.072. In addition, there were significant peaks on apoptosis induction at 4 and 6h after irradiation, and the morpholoigcal findings of the irradiated groups were typical apoptotic fragments in crypt cells that were hardly observed in the control group. Thus, apoptosis in crypt cells could be a useful in vivo model for studying radio-protective drug sensitivity or screening test, microdosimetric indicator and radiation-induced target organ injury. Since the apoptotic fragment assay is simple, rapid and reproducible in the range of 0.25 to 1 Gy, it will also be a good tool for evaluating the dose response of radiation-induced organ damage in vivo and provide a potentially valuable biodosimetry for the early dose prediction after accidental exposure.

• Journal of Society of Preventive Korean Medicine
• /
• v.3 no.2
• /
• pp.91-100
• /
• 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.

• Journal of Pharmaceutical Investigation
• /
• v.23 no.3
• /
• pp.165-177
• /
• 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.

• Journal of Veterinary Clinics
• /
• v.28 no.1
• /
• pp.101-107
• /
• 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.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.12
• /
• pp.5125-5135
• /
• 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.

• Animal cells and systems
• /
• v.5 no.1
• /
• pp.77-83
• /
• 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.

• Archives of Pharmacal Research
• /
• v.15 no.2
• /
• pp.169-175
• /
• 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.

• Proceedings of the Korean Society for Noise and Vibration Engineering Conference
• /
• 2008.04a
• /
• pp.264-267
• /
• 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.

• Proceedings of the Korean Society for Noise and Vibration Engineering Conference
• /
• 2007.11a
• /
• pp.436-441
• /
• 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.

• Membrane Journal
• /
• v.20 no.3
• /
• pp.197-202
• /
• 2010

Polyurethane diagnostic membranes were prepared to measure blood glucose level of diagnostics. Final absorbances at 680 nm through activated polyurethane membranes were measured at various concentration of glucose in blood. The end-point results of varing absorbance values as time (K/S) was found to have a linear relationship toward the blood glucose concentration. The effects of hematocrit on the glucose concentration measurements were examined. In low hematocrit, dose-response slope (DRS) values between gluose concentration and K/S values did not show the big differences compared to those in plasma. However, in high hematocrit (more than 40%) DRS values were considerably decreased.