• Radiation Oncology Journal
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• v.33 no.3
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• pp.233-241
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• 2015

Purpose: To compare volumetric modulated arc therapy of RapidArc with robotic stereotactic body radiation therapy (SBRT) of CyberKnife in the planning and delivery of SBRT for hepatocellular carcinoma (HCC) treatment by analyzing dosimetric parameters. Materials and Methods: Two radiation treatment plans were generated for 29 HCC patients, one using Eclipse for the RapidArc plan and the other using Multiplan for the CyberKnife plan. The prescription dose was 60 Gy in 3 fractions. The dosimetric parameters of planning target volume (PTV) coverage and normal tissue sparing in the RapidArc and the CyberKnife plans were analyzed. Results: The conformity index was $1.05{\pm}0.02$ for the CyberKnife plan, and $1.13{\pm}0.10$ for the RapidArc plan. The homogeneity index was $1.23{\pm}0.01$ for the CyberKnife plan, and $1.10{\pm}0.03$ for the RapidArc plan. For the normal liver, there were significant differences between the two plans in the low-dose regions of $V_1$ and $V_3$. The normalized volumes of $V_{60}$ for the normal liver in the RapidArc plan were drastically increased when the mean dose of the PTVs in RapidArc plan is equivalent to the mean dose of the PTVs in the CyberKnife plan. Conclusion: CyberKnife plans show greater dose conformity, especially in small-sized tumors, while RapidArc plans show good dosimetric distribution of low dose sparing in the normal liver and body.

• 대한예방의학회:학술대회논문집
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• 1994.02a
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• pp.431-438
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• 1994

As currently conducted, standard rodent bioassays do not provide sufficient information to assess carcinogenic risk to humans at doses thousands of times below the maximum tolerated dose. Recent analyses indicate that measures of carcinogenic potency from these tests are restricted to a narrow range about the maximum tolerated dose and that information on shape of the dose-response is limited in experiments with only two doses and a control. Extrapolation from high to low doses should be based on an understanding of the mechanisms of carcinogenesis. We have postulated that administration of the maximum tolerated dose can increase mitogenesis which, in turn. increases rates of mutagenesis and, thus, carcinogenesis. The animal data are consistent with this mechanism, because about half of all chemicals tested are indeed rodent carcinogens, and about 40% of the positives are not detectably mutagenic. Thus, at low doses where cell killing does not occur, the hazards to humans of rodent carcinogens may be much lower than commonly assumed. In contrast, for high-dose exposures in the workplace, assessment of hazard requires comparatively little extrapolation. Nevertheless. permitted workplace exposures are sometimes close to the tumorigenic dose-rate in animal tests. Regulatory policy to prevent human cancer has primarily addressed synthetic chemicals, yet similar proportions of natural chemicals and synthetic chemicals test positive in rodent studies as expected from an understanding of toxicological defenses, and the vast proportion of human exposures are to natural chemicals. Thus, human exposures to rodent carcinogens are common. The natural chemicals are the control to evaluate regulatory strategies, and the possible hazards from synthetic chemicals should be compared to the possible hazards from natural chemicals. Qualitative extrapolation of the carcinogenic response between species has been investigated by comparing two closely related species: rats and mice. Overall predictive values provide moderate confidence in interspecies extrapolation; however, knowing that a chemical is positive at any site in one species gives only about a 50% chance that it will be positive at the same site in the other species.

• Toxicological Research
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• v.34 no.2
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• pp.85-95
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• 2018

The term Butterfly tea refers to decoction of Mariposa christia vespertilionis leaves which is widely consumed by cancer patients throughout Malaysia and has gained a huge popularity among Malaysians, not only cancer patients but also researchers to discover the real potential of this plant. Herein, the study is aimed at evaluating the possible toxicity in 28-day subacute oral toxicity of ethanolic extract M. christia vespertilionis in male Sprague Dawley rats. The 28-day subacute toxicity study was conducted to detect the no-observed adverse effect level (NOAEL). In this study, a total of 30 rats were divided into the control, 5% DMSO (vehicle), low dose (75 mg/kg), medium dose (125 mg/kg) and high dose (250 mg/kg) groups. The extract was administered daily from day 1 until day 28. At the end of the study, the animals were humanely sacrificed and assessed for the effect extract of Mariposa christia vespertilionis leaves on body weight and relative organ weights and haematological, biochemical and histopathological parameters. The haematological and serum biochemical parameters for the assessment of kidney and liver injuries were carried out. Results of haematological and serum biochemistry results showed no changes in the control and treated groups. In the histopathology, evaluation of kidney tissues in all treated groups showed no significant (p > 0.05) lesions. In contrast to kidney, liver tissues showed significant differences (p < 0.05) in lesions observed in low dose (430 mg), medium dose (700 mg) and high dose (1480 mg) groups with very mild, mild and mild to moderate lesion of hepatic necrosis, in the respective groups, and very mild hepatic degeneration and hepatitis were scored in all three groups.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.6
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• pp.657-667
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• 2016

Critical limb ischemia (CLI) is one of the most severe forms of peripheral artery diseases, but current treatment strategies do not guarantee complete recovery of vascular blood flow or reduce the risk of mortality. Recently, human bone marrow derived mesenchymal stem cells (MSCs) have been reported to have a paracrine influence on angiogenesis in several ischemic diseases. However, little evidence is available regarding optimal cell doses and injection frequencies. Thus, the authors undertook this study to investigate the effects of cell dose and injection frequency on cell survival and paracrine effects. MSCs were injected at $10^6$ or $10^5$ per injection (high and low doses) either once (single injection) or once in two consecutive weeks (double injection) into ischemic legs. Mice were sacrificed 4 weeks after first injection. Angiogenic effects were confirmed in vitro and in vivo, and M2 macrophage infiltration into ischemic tissues and rates of limb salvage were documented. MSCs were found to induce angiogenesis through a paracrine effect in vitro, and were found to survive in ischemic muscle for up to 4 weeks dependent on cell dose and injection frequency. In addition, double high dose and low dose of MSC injections increased vessel formation, and decreased fibrosis volumes and apoptotic cell numbers, whereas a single high dose did not. Our results showed MSCs protect against ischemic injury in a paracrine manner, and suggest that increasing injection frequency is more important than MSC dosage for the treatment CLI.

• Journal of Dental Anesthesia and Pain Medicine
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• v.22 no.5
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• pp.349-356
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• 2022

Background: Awake fiberoptic intubation (AFOI) is the procedure of choice for securing the airway in patients with a difficult airway when undergoing surgeries under general anesthesia. An ideal drug would not only provide conscious sedation but also maintain spontaneous ventilation, smooth intubation conditions, and stable hemodynamics. We compared the effects of dexmedetomidine alone and dexmedetomidine in combination with fentanyl at a dose lower than the standard dose for achieving conscious sedation during AFOI in difficult airway patients undergoing oral cancer and dental surgeries. Methods: We included 68 adult patients undergoing AFOI. The patients were randomized in two groups, wherein Group D received intravenous dexmedetomidine 1 ㎍/kg and Group DF received dexmedetomidine 0.5 ㎍/kg and fentanyl 1 ㎍/kg. The outcomes measured were airway obstruction score, intubation scores, fiberoptic intubation comfort score, sedation score, and hemodynamic variables. Results: Low-dose dexmedetomidine with fentanyl showed similar results as those with the standard dose of dexmedetomidine in terms of airway obstruction, vocal cord movement, degree of cough, degree of limb movements, and intubation comfort. However, the sedation achieved and incidence of hypotension and bradycardia were higher in Group D than in Group DF. Conclusions: A low dose of dexmedetomidine-fentanyl provides satisfactory intubation conditions as those with a standard dose of dexmedetomidine in AFOI, thereby avoiding bradycardia, hypotension, and sedation.

• Journal of Radiation Protection and Research
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• v.23 no.3
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• pp.149-157
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• 1998

An analysis has been performed to estimate the additional number of workers and the additional collective dose in man-cSv which would be required, nuclear industry-wide as a result of reducing individual dose limit. This analysis can be extended to the reduction in the dose limits recommended by ICRP Publ.60 and BEIR V report as well as the proposed dose limits by regulatory authorities. An industry-wide database was employed in the analysis based on a summary of industry-wide occupational radiation exposure compiled by the Korea Radioisotope Association. Correlation model was employed to compute the affects of setting specific annual individual dose limits. In this study, we have addressed worker non-productivity while in the radiation environment on a parametric or 'sensitivity analysis' basis. This alleviates the need for developing such data underlying a summation of many individual tasks at many nuclear facilities. It has the advantage that very low non-productivity assumptions can readily be defended as conservative, in that it is difficult to approach such low worker non-productivity factors even in the best of environments in any industry. On a per facility basis, for calendar year 1997, the number of workers required would be increased from 231 workers to 269 workers and collective man-cSv dose would be also increased by approximately fourteen percent if the individual dose limit was reduced to 2 cSv/y and an individual worker non-productivity fraction of 0.1 is assumed.

• 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.

• Development and Reproduction
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• v.21 no.2
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• pp.121-130
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• 2017

4-Nonylphenol (NP) is a surfactant that is a well-known and widespread estrogenic endocrine disrupting chemical (EDC). Although it has been known that the affinity of NP to ERs is low, it has been suggested that low-dose NP has toxicity. In the present study, the endocrine disrupting effects on reproduction, and the weight of gonads, epididymis, and uterus were evaluated with the chronic lower-dose NP exposing. This study was designed by following the OECD test guideline 443 and subjected to a complete necropsy. In male, NP had an effect on the weight of the testis and epididymis in both $F_0$ and $F_1$. In females, NP decreased the weight of ovary and uterus in $F_0$ but not in pre-pubertal $F_1$ pubs. Fertility of male and female in $F_0$ or $F_1$ was no related with NP administration. The number of caudal-epididymal sperm by body weight (BW) was not different between groups in both $F_0$ and $F_1$. Besides, the difference of the sperm number between generations was not detected. The number of ovulated oocytes was similar between groups in $F_0$, but significantly decreased in NP 50 group of $F_1$. The litter size and sex ratios of offspring in $F_1$ and $F_2$ were not different. The accumulated mating rate and gestation period were not affected by the NP administration. Those results shows that chronic lower-dose NP administration has an effect of endocrine disruptor on the weight of gonads and epididymis of $F_0$ and $F_1$ but not in reproduction. Based on the results, it is suggested that chronic lower-dose NP exposing causes endocrine disruption in the weight of gonad and epididymis but not in the reproductive ability of next generations.

• IMMUNE NETWORK
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• v.6 no.2
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• pp.93-101
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• 2006

Background: Memory T lymphocytes of the immune system provide long-term protection in response to bacterial or viral infections/immunization. Ag concentration has also been postulated to be important in determining whether T cell differentiation favors effector versus memory cell development. In the present study we hypothesized that naive Ag-specific $CD4^+$ T cells briefly stimulated with different Ag doses at the primary exposure could affect establishment of memory cell pool after secondary immunization. Methods: To assess this hypothesis, the response kinetics of DO11.10 TCR $CD4^+$ T cells primed with different Ag doses in vitro was measured after adoptive transfer to naive BALB/c mice. Results: Maximum expansion was shown in cells primarily stimulated with high doses of ovalbumin peptide $(OVA_{323-339})$, whereas cells in vitro stimulated with low dose were expanded slightly after in vivo secondary exposure. However, the cells primed with low $OVA_{323-339}$ peptide dose showed least contraction and established higher number of memory cells than other treated groups. When the cell division was analyzed after adoptive transfer, the high dose Ag-stimulated donor cells have undergone seven rounds of cell division at 3 days post-adoptive transfer. However, there was very few division in naive and low dose of peptide-treated group. Conclusion: These results suggest that primary stimulation with a low dose of Ag leads to better memory $CD4^+$ T cell generation after secondary immunization. Therefore, these facts imply that optimally primed $CD4^+$ T cells is necessary to support effective memory pool following administration of booster dose in prime-boost vaccination.

• Development and Reproduction
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• v.22 no.1
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• pp.85-94
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• 2018

Endocrine disruptors have been concerned in toxicology but now challenged as physiological point especially concerned with exposing dose and period. In this study the low-dose chronic administration of di(2-ethylhexyl) phthaltae (DEHP) during reproductive period was examined to evaluate the possible roles. Adult male and female CD-1 mice were exposed to DEHP with drinking water containing $133{\mu}g/L$ and $1,330{\mu}g/L$ DEHP in water according to OECD 433 guide line and sacrificed just after weaning. The weights of uterus and ovary were decreased by drinking of $1,330{\mu}g/L$ DEHP water. There was not adverse effects on either accumulated mating rate and mating rate depend on estrus stage, pregnancy duration, and sex ration at birth. However, the accumulated rate of successful delivery and litter size were significantly high at $1,330{\mu}g/L$ DEHP water. The number of epididymal sperm was significantly increased by drinking of $1,330{\mu}g/L$ DEHP water. In addition, the number of follicles (primary, secondary, tertiary) were more many than control at $1,330{\mu}g/L$ DEHP water drunk mother. Though further studies are needed to identify what are the mechanism of DEHP in folliculogenesis and spermatogenesis. From this study we firstly report the effect of low-dose chronic administration of DEHP with drinking could change the ovarian follicle population size and spermatogenesis rate. Put together, those finding is different from previous high-dose effects and suggest the physiological role of DEHP in gonads and uterus.