• Title/Summary/Keyword: Dose Response Curve

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Intra-tracheal Administration of the Disinfectant Chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) in a Mouse Model to Evaluate a Causal Association with Death (마우스의 기도 내 점적을 통한 가습기살균제 CMIT/MIT와 사망 간의 원인적 연관성에 관한 연구)

  • Kim, Hayoung;Chung, Yonghyun;Park, Yeongchul
    • Journal of Environmental Health Sciences
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    • v.43 no.4
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    • pp.247-256
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    • 2017
  • Objectives: The deaths of Korean victims exposed to the disinfectant CMIT/MIT have remained unresolved. This is mainly due to a lack of concordance between the few available toxicity tests and the abundant epidemiological data, making it difficult to establish a cause-and-effect relationship. Therefore, this study was carried out to investigate any potential associations between CMIT/MIT exposure and death. Methods: Groups of experimental and control C57BL/6 mice were instilled (in the trachea) with chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a visual instillobot. CMIT/MIT was instilled over a period of three days and eight weeks, respectively, to achieve acute and chronic exposures. A threshold dose-response model was applied for estimating the threshold level as one line of evidence for a causal association between CMIT/MIT and death. Results: An acute exposure of 1.2 mg ai/kg/day of CMIT/MIT was estimated to reflect the threshold for death. The dose-response curve with this threshold showed a very steep slope and a narrow range of CMIT/MIT exposures. The narrow range of CMIT/MIT exposures, in particular, indicated an evident boundary between survival and death, thus implicating a strong causal association. A similar threshold dose-response relationship observed following acute exposure was also seen following chronic exposure to CMIT/MIT. Airborne disinfectant exposure was visible as minimal or mild lung damage with no fibrosis, as shown by histopathological tests. However, many observations are considered to be functional respiratory tract or lung failure due to death, as observed in necropsies of the mice that died due to CMIT/MIT exposures. Conclusions: There are two strong lines of evidence for a causal association between death and CMIT/MIT exposure: 1) The threshold dose-response curve, with a very steep slope and a narrow range of CMIT/MIT exposures showing a visible boundary between survival and death; and 2) many cases of functional respiratory or lung failure.

Low Dose Effect and Non Monotonic Dose Responses(NMDRs) and its Medical Meaning - Focusing on A New Paradigm of Dose-Response Relationship - (Low Dose Effect와 Non Monotonic Dose Responses(NMDRs) 그리고 의학적 의미 - 용량-반응관계의 새로운 패러다임을 중심으로 -)

  • Sung, Angela Dongmin;Shin, Jeeyoun;Lee, Seungeun;Park, Songmi;Oh, Yeonji;Lee, Sundong
    • Journal of Society of Preventive Korean Medicine
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    • v.20 no.1
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    • pp.145-159
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    • 2016
  • Objectives : The aim was to investigate the characteristics of low dose effect and non monotonic dose responses(NMDRs) and to predict the influence it might have on the health and medicine, traditional Korean medicine. Methods : By investigating recently published major literatures related to low dose effect and NMDRs, the definition, mechanism, major related fields, and the influence on public health and medicine has been categorized and summarized. Results : Although there are still heated debates about the definition of low dose, it implies the biological responses in environmental exposure level and the NDMDRs means the nonlinear relationship between the dose-response in the slope sign change. Also, it implies the new form of the curve showing a U, reverse U shape, and the slop sign constantly changing showing various forms. This mechanism is because the two acceptor shows opposing effects to toxic materials and the affinity is different along with the numerical value that increase and decrease being different. These characteristics generally appear in endocrine disrupters such as bisphenol A, agricultural pesticides, metal, and radiation. The research field in the public health and medical treatment is obesity, problems in metabolism, growth hormone treatment, climacteric treatment, breast cancer, intake of Korean traditional medicine for pregnancy, menopause and phytoestrogen. Conclusions : As a result of discussing implications, NMDRs is a particular effect in low dose and heated debates surround this response, research is being conducted surrounding the field of obesity, problems in metabolism, growth hormone treatment, climacteric treatment, breast cancer, intake of Korean traditional medicine for pregnancy, menopause, and phytoestrogen. More research and interest in needed as it can have a massive influence in the public health and medicine.

Induction of Mouse Epidermal ODC by TPA and Inhibition by Plant Flavonoids, in Skin Tumor Promotion (다단계 발암과정 중 Promotion 단계에서의 TPA에 의한 Mouse Epidermal ODC의 유도 및 약물에 의한 차단효과)

  • 김미경;장일식;정문호
    • Journal of Environmental Health Sciences
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    • v.19 no.3
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    • pp.64-73
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    • 1993
  • The study was conducted to investigate the mechanism of tumor promotion as the time courses and the doses of promoter, and the effect of plant fiavonoids on the TPA-induced ODC responses. The results are summarized as follows: 1. A single, toppical application of 17 nmole of the potent tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate, resulted in an induction of mouse epidermal Ornithine Decarboxylase with a peak at 5 hours after treatment and maximized 5.1 times as large as ODC activities of control. 2. Dose-response curve indicated that the tumor promotion increases proportionally between 1.7 and 170 nmole of TPA. This dose dependency relationship indicated that the ability of TPA to stimulate ODC is linked its ability to promote tumors. 3. Naturally occurring plant fiavonoids with anticarcinogenic and antipromotional activities were tested for their abilities to inhibit ODC response induced by skin tumor promoter TPA. Intra peritoneal administration of fiavonoids compounds (rutin, naphthofiavone, baicalein, quercitrin) and herbal drugs (sophorae rios, crataegi fructus, armeniacae semen) inhibited 17 nmole TPA-induced ODC activities in mouse epidermis in vivo.

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Dosimetric Characteristics of Flexible Radiochromic Film Based on LiPCDA

  • Jung, Seongmoon;Cho, Jin Dong;Kim, Jung-in;Park, Jong Min;Choi, Chang Heon
    • Progress in Medical Physics
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    • v.32 no.4
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    • pp.179-184
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    • 2021
  • This study aimed to determine the optimal thickness of the active layer and scan mode for a flexible radiochromic film (F-RCF) based on the active lithium salt of pentacosa-10,12-diynoic acid (LiPCDA). F-RCFs of 90, 120, 140, and 170-㎛ thickness were fabricated using LiPCDA. Several pieces of the F-RCFs were exposed to doses ranging from 0 to 3 Gy. Transmission and reflection modes were used to scan the irradiated F-RCFs. Their dose-response curves were obtained using a second-order polynomial equation. Their sensitivity was evaluated for both scanning modes, and the uniformity of the batch was also examined. For both the transmission and reflection modes, the sensitivity increased as the film thickness increased. For the reflection mode, the dose response increased dramatically under 1 Gy. The value of the net optical density varied rapidly as the thickness of the film increased. However, the dose-response curves showed a supralinear-curve relationship at doses greater than 2 Gy. The sensitivity of the reflection scan at doses greater than 2 Gy was higher than that of the reflection scan within 0-2 Gy. The sensitivity steadily decreased with increasing doses, and the sensitivity of the two modes was within 0.1 to 0.2 at 2 Gy and was saturated beyond that. For the transmission scan, the sensitivity was approximately 0.2 at 3 Gy. For the intra-batch test result, the maximum net optical density difference of the intra-batch was 5.5% at 2 Gy and 7.4% at 0.2 Gy in the transmission and reflection scans, respectively. In the low-dose range, film thickness of more than 120-㎛ was proper in the transmission mode. In contrast, the transmission mode showed a better result compared to the reflection mode. Therefore, the proper scan mode should be selected according to the dose range.

Radiosensitivity and Dobe-Survival Characteristics of Crypt Cells of Mouse Jejunum (마우스공장 소낭선세포의 방사선 감수성에 관한 실험적 연구)

  • Huh, Seung-Jae;Park, Charn-Il
    • Radiation Oncology Journal
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    • v.3 no.1
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    • pp.9-12
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    • 1985
  • To determine the radiosensitivity and dose-survival characteristics of jejunal crypt cells, experimental study was done using total 40 mice. Single irradiation of 1,000 rad to 1,600rad was delivered to whole bodies of mice, using a cesium 137 animal irradiator. The number of regenerating crypts per jejunal circumference was counted, by using a jejunal crypt cell assay technique, and dose response curve was measured. The average number of jejunal crypt Per circumference in control group was $140\pm10$. Mean lethal dose$(D_0)$ of moose jejunal crypt cell was 135rad.

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Exocrine Secretory Responsiveness of Dispersed Pancreatic Acini to Secretagogues in Camostat-treated Rats (Camostat 투여 흰쥐 이자 외분비선의 분비자극물질에 대한 반응성)

  • Kim, Chul;Kim, Dong-Goo;Kim, Kyung-Hwan
    • The Korean Journal of Pharmacology
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    • v.30 no.2
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    • pp.205-215
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    • 1994
  • It is well known that chronic stimulation with CCK gives rise to growth of exocrine pancreas and to increased content of enzyme proteins in pancreas. However, littls Is known about changes of the secretory function of exocrine pancreas which has been chronically stimulated with CCK, especially about the responsiveness to secretagogues such as CCK, caerulein and carbachol. The present study was performed to investigate the effect of camostat on secretory profiles and the responsiveness to secretagogues of exocrine pancreas by observing in vitro amylase release stimulated by cholecystokinin-octapeptide(CCK-8) and carbachol in dispersed isolated pancreatic acini from camostat-treated rats for 4 or 10 days. The results summarized as follows : 1) The maximal effective concentration of CCK-8 in amylase release in the camostat treated group was greater than control group, but that of carbachol was not different between groups. 2) Analysis of the stimulated amylase release as the percentage of the maximal response revealed that camostat treatment caused right-shift of the dose-response curve of CCK-8. Camostat did not cause significant changes in the dose-response curve of carbachol. 3) There were considerable increases in the amylase release in the camostat-treated group, compared to the control when acini were stimulated with CCK-8 $10^{-9}\;M$ and carbaochol $10^{-6}\;M$, and higher concentrations. 4) There was a reverse correlation between the tissue content and the maximal release(percent of the total content) of amylase. These results suggest that chronic exposure of exocrine pancreas to increased endogenous CCK can enhance the responsiveness of exocrine enzyme secretion to secretagogues, especially at higher concentrations of CCK and carbachol.

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Energy Response in Chemiluminescence Dosimetry with Sugar and Sorbite

  • Jun, J.S.;Guggenberger, R.;Dalheimer, A.
    • Nuclear Engineering and Technology
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    • v.33 no.6
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    • pp.626-637
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    • 2001
  • A series of study on energy dependence in chemiluminescence dosimetry with sugar and sorbite produced in two different countries was carried out administering a dose of 5 Gy to the samples at six different mean photon energies of 30, 50, 80, 130, 662 and 1250 keV. The results revealed distinct energy dependence of chemiluminescence(CL) output of sugar and sorbite. Although the energy dependence, in general, could be fitted by a polynomial of (os E, with I being radiation energy, up to cubic term, we reached a conclusion that the adoption of a fitting function, $y_{R}$$^{=a}$.(1-e $^{-b.logE}$)$^{c}$ +d, deduced from theoretical energy response curve calculated as the ratio of the mass energy absorption of the samples of interest to the soft tissue is more reasonable and rational. Herecoefficients $y_{R}$ is CL intensity, and a, b, c and d are constants to be determined in the fitting process. Energy dependence of relative sensitivities of one sample to the other, discrepancy in sensitivities of the samples from the two countries, and prominent grain size effect in Sorbitol were also shown.shown.

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Uterotrophic Assay Using Ovariectomized Female Rats with Sub-cutaneous Administration

  • Kim, Hyung-Sik;Han, Soon-Young;Lee, Rhee-Da;Kil, Kwang-Sup;Park, Kui-Lea
    • Biomolecules & Therapeutics
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    • v.8 no.1
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    • pp.78-83
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    • 2000
  • The objective of this study was to prevalidate the Organization for Economic Cooperation and Development's (OECD) rodent uterotrophic assay as a test method for screening of potential endocrine disrupting chemicals (EDCs). This study was conducted exactly as described in the OECD protocol documents. A positive control substance, 17$\alpha$-ethinyl estradiol (EE), was administered daily for three days to ovariectomized (OVX) Sprague-Dawley rats at various doses for determine the dose-response curve. Additionally, a pure antiestrogenic chemical, ZM189, 154 was administered to OVX rats at the same time EE to determine the effectiveness of the material against blocking the estrogenic effects of EE. At higher concentration of EE (10 $\mu\textrm{g}$/kg), a statistically significant difference in body weight gain and food consumption was observed compared to vehicle controls. In uterine responses, EE produced a dose-related increase in uterus weights compared to vehicle control. These increases were statistically significant at the >1.0 $\mu\textrm{g}$/kg doses. However, a similar dose-response relationship was not observed in vagina weight. A comparison of the two groups receiving ZM189,154 (0.1 and 1.0 mg/kg) with 0.3 $\mu\textrm{g}$/kg of EE and the group receiving only 0.3 $\mu\textrm{g}$/kg of EE showed dose-related decreases in uterus weights. However, statistical significance was shown in 1.0 mg/kg of ZM189,154. In conclusion, administration of EE produced a dose-related increase in uterine (wet and blotted) weights. Additionally, the 1.0mg/kg dose of ZM189,154 was effective in blocking the estrogenic activity of EE. These data suggest 3-day uterotrophic assay using OVX rats may serve as a good tool for EDCs screening.

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Radiation Effect on Mouse Jejunal Crypt Cells by Single and Split Irradiation (단일조사와 분할조사시 마우스 공장 소낭선세포의 방사선효과에 관한 실험적 연구)

  • Koh Byung Hee;Hahm Chang Kok;Kim Jung Jin;Park Chan Il
    • Radiation Oncology Journal
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    • v.3 no.1
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    • pp.1-8
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    • 1985
  • To determine the dose·survival and repair characteristics of the jejunal crypt cells, experimental study was carried out using total 70 mice. Single or split irradiations of 1,100 to 2,200 rad were delivered to whole bodies of $C_{57}$ BL mice, using a cesium 137 animal irradiator and those mice were sacrificed after 90 hours. The number of regenerating crypts per jejunal circumference was counted by a jejunal crypt cell assay technique and dose·response curve was measured. The results were as follows : 1. The average number of jejunal crypts per circumference in control group was 140. In a single irradiation group, the number of regenerated jejunal crypts was, 125, 56, 2 in each subgroup of 1,100 rad, 1,400 rad and 1,800 rad respectively. In split irraiation group, it was 105,44,2 in each subgroup of 1,400rad 1,800rad and 2,200rad respectively. 2. Mean lethal dose of mouse jejunal crypt cell was 167 and 169 rad respectively in a single and split irradiation. 3. Repair dose of sublethal damage was 280 rad. 4. Sublethal damage was completely repaired within 4 hours between the split dose of irradiation.

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The Reduction ways of Medicine Material Costs of Nuclear Medicine In Vitro (핵의학 체외검사의 진료재료비용 절감 방안)

  • Song, Hun-Kang;Seo, Jung-Mi;Yang, Joon-Ho;Kim, Eun-Jung;Kim, Chang-Ho
    • The Korean Journal of Nuclear Medicine Technology
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    • v.15 no.2
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    • pp.111-115
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    • 2011
  • Purpose: In vitro uses dose response curve with 6 to 7 standard concentrations in every examination to analyze examination results and this use of dose response curve comprises a large portion of the consumption of medicine material. At this present, some ones of in-hospital examination items have shown mostly low result of distribution in the analyzed features and these examinations have been judged that it would be unnecessary to use the last standard concentration. Hence, this study selects those examination items showing low result of distribution and reviews the cases contributed to less consumption of medicine material and revenue growth of hospital by reduction of medicine material used in the place of the last standard concentration. Materials and Methods: The study was made targeting 11 examination items out of total 43 items of the in-hospital examination and since these examination items were mostly low in the features as the examination results of patients or the examination results were distributed to show lower concentration than the previous last standard concentration, it carried out the examination without using the last standard concentration, which could generate the effect to reduce medicine material (examination tube) used in the last standard concentration as many as the number of examination carried out. For this, it examined the number of medicine material reduction by month during the period from July, 2009 to February, 2011 and estimated the reduction amount of medicine material calculated the number of reduction by the unit cost of medicine material as well as the profit generated by the reduced medicine material to use for the medicine material of patient examination. Results: The total number of medicine material reduced during the period from July, 2009 to February, 2011 was 3,131 pieces, which had the effect to reduce the medicine material equivalent to about 31 kits of reagent. To calculate this by the unit cost of the medicine material, it analyzed to reduce about 6.4 million won of medicine material cost. Also the reduced medicine materials were used for medicine materials of patient examination and this was analyzed to generate about 13.75 million won of profit based on the ABC cost accounting. Conclusion: It showed no problem in the analysis of examination result even without using the last standard concentration regarding those examination items with low distribution of the patient examination result. For these examination items, it was able to reduce medicine material used for the last standard as many as the number of examination carried out. Also, the adjustment of concentration range was found to have no problem in the reliability of examination result. Therefore, this case will be applicable in those occasions of when the analysis of patient examination result is mostly distributed at the lower level or when an examination with the distribution of patient results in the range of lower concentration than the previous last standard concentration is carried out and this is considered to increase the efficiency in the use of medicine material in vitro as well as contribute to the profit of hospitals.

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