• Title/Summary/Keyword: Chronic Toxicity

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Genotoxicological Safety of Hot Water Extracts of the ${\gamma}$-Irradiated Glycyrrhizae Radix, Aurantii nobilis Pericarpium and Bupleuri Radix in vitro (감마선조사 감초, 진피(陳皮) 및 시호 열수 추출물의 in vitro 유전독성학적 안전성 평가)

  • Jo, Sung-Kee;Ham, Yeon-Ho;Park, Hae-Ran;Oh, Heon;Byun, Myung-Woo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.30 no.6
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    • pp.1137.2-1245
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    • 2001
  • The ${\gamma}$-irradiated medicinal herbs were examined the genotoxicological safety to consider the possibility of application of the irradiation technology for hygienic purpose. The three medicinal herbs -Glycyrrhigae Radix, Aurantii nobilis Pericarpium and Bupleuri Radix- were irradiated with ${\gamma}$ -rays at the practical dosage of 10 kGy. The hot water extracts of the irradiated herbs were examined in two short-term in vitro tests: (1) Ames test in Salmonella typhimurium TA98 and TA100, (2) Micronucleus test in cultured Chinese hamster ovary(CHO) cells. In the Salmonella reversion assays both with and without metabolic activation, the number of revertant colonies was not increased with each extract from the irradiated herbs, compared with negative controls. No significant difference in formation of the colonies was observed between non-irradiated and 10 kGy-irradiated herbs. These results indicated that no mutagenicity of the irradiated herbs was detected. In the micronucleus tests in cultured CHO cells, the incidences of micronucleus were not increased with irradiated herbs, and no significant difference in the incidences was observed between non-irradiated and irradiated herbs. These results indicated that no cytogenetic toxicity of the irradiated herbs was detected. The results of the two in vitro tests suggest that the irradiated herbs do not show mutagenic effects and cytogenetic toxicity. Further tests of in vivo genotoxicity and chronic toxicity are needed to determine the safety of the herbs irradiated with ${\gamma}$ -rays at practical doses.

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Biological Study on the Increment of Survival Rate during Early Life Cycle in th Rockfish, Sebastes schlegeli (Telostei: Scorpaenidae) - I. Effects of Ammonia on Survival and Growth of the Larvae and Juveniles Stage (조피볼락, Sebastes schlegeli의 초기생활사 동안 생존율 향상을 위한 생물학적 연구 - I. 자어의 생존과 성장에 미치는 암모니아의 영향)

  • Chin, Pyung;Shin, Yun-Kyung;Kim, Hak-Gyoon;Lee, Jeong-Sick;Kim, Hyung-Soo
    • Korean Journal of Ichthyology
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    • v.10 no.1
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    • pp.98-105
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    • 1998
  • The effect of ammonia on survival and growth of the larval rockfish, Sebastes schlegeli was examined by a static renewal bioassay method. The tolerance of larvae to ammonia toxicity was more sensitive at the early larvae, but increased with the development of larvae. In 14 day-old-larvae after parturition, the mortality with treatment of each concentration of ammonia was 5% at control group and 0.0112 $NH_3$mg/l, whereas it was increased up to 27.5% at exposure group of 0.1230 $NH_3$mg/l with higher concentration. Regression equation between ammonium concentration(X) and mortality(Y) was followed; Y=0.516+3.482 X($r^2=0.4737$, P<0.01). The NOEC(no-observable-effect concentration) and LOEC (lowest-observable-effect concentration) to mortality compared to control group were 0.100 $NH_3mg/l$ and 0.1230 $NH_3$mg/l, respectively and chronic value(ChV) which is the geometric mean of the NOEC and LOEC was 0.1110 $NH_3$mg/l. Body length after 7-days exposure in control group, 0.0112 $NH_3$mg/l and 0.1230 $NH_3$mg/l were 7.8325mm, 7.700mm and 7.05mm, respectively. The NOEC, LOEC and chronic value(ChV) were 0.0335 $NH_3$mg/l, 0.0558 $NH_3$mg/l and 0.0432 $NH_3$mg/l, respectively.

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Hepatoprotective effect of Hippocampus abdominalis hydrolysate (Hippocampus abdominalis 유래 단백질 가수분해물의 간 보호 효과)

  • Son, Moa;Moon, Jun young;Park, Sanggyu;Cho, Moonjae
    • Journal of Applied Biological Chemistry
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    • v.59 no.3
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    • pp.265-271
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    • 2016
  • Recently, liver damage contributes to big percentage of the morbidity and mortality rates worldwide. Excessive intake of alcohol is one of the major causes of liver injury. When liver injury is repeated and becomes chronic, it leads to development of fibrosis and cirrhosis. In the liver, TGF-${\beta}$ is a profibrogenic cytokine, which participates in various critical events cause liver fibrosis. Seahorse (Hippocampus abdominalis) is a common traditional Chinese medicine and has been widely used for centuries. Seahorse has been known to have a variety of bioactivities, such as anti-oxidant, anti-fatigue, and anti-tumor. Peptide is one of the main compounds of seahorse. In this study, we isolated enzymatic hydrolysate from seahorse H. abdominalis by alcalase hydrolysis and investigated the effect of the hydrolysate on liver injury. In the present in vitro studies, the hydrolysate increases cell viability of Chang cells and protects Huh7 cells from ethanol toxicity. In addition, the hydrolysate inhibits TGF-${\beta}$-induced responses. In vivo studies show that the pretreatment of hydrolysate reduces alcohol-induced increases of serum Glutamic oxaloacetic acid transaminase and Glutamic pyruvate transaminase activities and increases liver weight and body weight. These results suggest that seahorse may have a hepatoprotective effect.

Definitive radiotherapy with or without chemotherapy for clinical stage T4N0-1 non-small cell lung cancer

  • Kim, Yeon Joo;Song, Si Yeol;Jeong, Seong-Yun;Kim, Sang We;Lee, Jung-Shin;Kim, Su Ssan;Choi, Wonsik;Choi, Eun Kyung
    • Radiation Oncology Journal
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    • v.33 no.4
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    • pp.284-293
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    • 2015
  • Purpose: To determine failure patterns and survival outcomes of T4N0-1 non-small cell lung cancer (NSCLC) treated with definitive radiotherapy. Materials and Methods: Ninety-five patients with T4N0-1 NSCLC who received definitive radiotherapy with or without chemotherapy from May 2003 to October 2014 were retrospectively reviewed. The standard radiotherapy scheme was 66 Gy in 30 fractions. The main concurrent chemotherapy regimen was $50mg/m^2$ weekly paclitaxel combined with $20mg/m^2$ cisplatin or AUC 2 carboplatin. The primary outcome was overall survival (OS). Secondary outcomes were failure patterns and toxicities. Results: The median age was 64 years (range, 34 to 90 years). Eighty-eight percent of patients (n = 84) had an Eastern Cooperative Oncology Group performance status of 0-1, and 42% (n = 40) experienced pretreatment weight loss. Sixty percent of patients (n = 57) had no metastatic regional lymph nodes. The median radiation dose was EQD2 67.1 Gy (range, 56.9 to 83.3 Gy). Seventy-one patients (75%) were treated with concurrent chemotherapy; of these, 13 were also administered neoadjuvant chemotherapy. At a median follow-up of 21 months (range, 1 to 102 months), 3-year OS was 44%. The 3-year cumulative incidences of local recurrence and distant recurrence were 48.8% and 36.3%, respectively. Pretreatment weight loss and combined chemotherapy were significant factors for OS. Acute esophagitis over grade 3 occurred in three patients and grade 3 chronic esophagitis occurred in one patient. There was no grade 3-4 radiation pneumonitis. Conclusion: Definitive radiotherapy for T4N0-1 NSCLC results in favorable survival with acceptable toxicity rates. Local recurrence is the major recurrence pattern. Intensity modulated radiotherapy and radio-sensitizing agents would be needed to improve local tumor control.

EFFECTS OF FLUORIDE MOUTHRINSE ON CELL ACTIVITY OF GINGIVAL FIBROBLASTS OF CHILDREN (불소양치용액이 소아 치은 섬유아세포의 세포활성에 미치는 영향에 관한 연구)

  • Lee, Dong-Hyun;Lee, Kwang-Hee
    • Journal of the korean academy of Pediatric Dentistry
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    • v.24 no.1
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    • pp.204-219
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    • 1997
  • The use of fluoride is one of the most effective methods for caries prevention. Fluoridation of public water supply has been recognized, for many years, as an effective way to reduce dental caries. The fluoride supplement has been recommended when the natural fluoride was unavailable or below the optimal range. However the mechanism of caries prevention by fluoride has not yet been clarified and it is well known that an overdose of fluoride results inacute and chronic toxicity, especially dental fluorosis. Fluoride mouthrinsing solution is widely used in dentistry due to its effectiveness in carrying anticariogenic action. Understanding the effects of fluoride mouthrinsing solution on human gingival fibroblasts will provide the safety rationale for its use during the caries preventive therapy. The purpose of this study was to evaluate the cytotoxic effect of fluoride mouthrinsing solution on the human gingival fibroblast in vitro. The human gingival fibroblasts were cultured from healthy gingiva on the extracted deciduous teeth of children. Cells were inoculated into a 24-well plate with $1{\times}10^4cells/well$ of medium at $37^{\circ}C$, 100% humidity, 5% $CO_2$ incubator for 24 hours. And the cells were counted by using the hemocytometer at each designed study. Human gingival fibroblasts were cultured in growth medium after one minute application range of 0.02%-0.2% NaF solution and 0.1% $SnF_2$ solution. The cells used in this study were between fifth to eighth passage number. The cell morphology was examined by inverted microscope and cell proliferation was measured by incorporating $[^3H]$-thymidine into DNA. DNA synthesis by human gingival fibroblasts was assessed by $[^3H]$-thymidine uptake assays while the cell activity was measured by MTT assay. Each concentrated fluoride mouthrinsing solution was estimated for its biocompatability with fibroblasts by the tissue culture technique. The results of this study were as follows : 1. It was observed that at 0.05%, 0.2% NaF mouthrinsing solution the cytoplasmic processes became globular. When 0.1% $SnF_2$ mouthrinsing solution was applied, the cytoplasmic process and cell morphology were disappeared. 2. DNA synthetic activity was reduced regardless of the concentration of the fluoride mouthrinsing solution. However, the result is statistically insignificant except 0.1% $SnF_2$ mouthrinsing solution(p<0.05). 3. Our results indicate that 0.02%, 0.05% concentrations of NaF mouthrinsing solution caused minimal cytotoxicity. But 0.2% NaF and 0.1% $SnF_2$ concentration were a significant difference between the cell activity in the experimental group and control group (p<0.05). 4. After appling 0.05% & 0.02% NaF fluoride mouthrinsing solution, cell activity was restored to the control groups level according to incubating time. The results suggest that direct exposure to fluoride solution inhibits gingival fibroblast activity. Therefore, for the most effective use of fluoride use, lowering the concentration of fluoride mouthrinsing is advisable because it maintains biocompatability and free ion in the oral fluid.

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Removal of Cyanogenic Compounds in Apricot Kernel during Heating Process (가열조리방법을 통한 행인 내 시안화합물의 저감화)

  • Do, Byung-Kyung;Kwon, Hoon-Jeong;Lee, Dong-Ha;Nah, Ahn-Hee;Choi, Youn-Ju;Lee, Sook-Yeon
    • Journal of Food Hygiene and Safety
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    • v.22 no.4
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    • pp.395-400
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    • 2007
  • Apricot Kernel, consumed as herbal medicine, contains amygdalin which generate HCN upon hydrolysis. Dyspnea was reported by ingesting large amount of apricot kernel, and neurological disorders such as tropic ataxic neuropathy or konzo were known as chronic toxicity of amygdalin. Other cyanogen containing plants, including flaxseed and almond, are consumed as food around the world. Moreover, some of them are promoted as functional food, leading to higher consumption, and posing health risk by cyanogenic components. The objective of this study was to find a method for the reduction of the cyanogenic compound, using apricot kernel as a model food. The most effective reduction was obtained by boiling the slices of the kernel for one hour in pH 1 HCl solution, showing 90% removal. However, the common process known to reduce the cyanogen contents, i.e., long incubation at the low temperature, did not show significant change in cyan concentration. Our data contribute to the safety of the plants containing cyanogenic compounds if they were to be developed as foodstuff.

Suggestion for a New Grading Scale for Radiation Induced Pneumonitis Based on Radiological Findings of Computerized Tomography: Correlation with Clinical and Radiotherapeutic Parameters in Lung Cancer Patients

  • Kouloulias, Vassilios;Zygogianni, Anna;Efstathopoulos, Efstathios;Victoria, Oikonomopoulou;Christos, Antypas;Pantelis, Karaiskos;Koutoulidis, Vassilios;Kouvaris, John;Sandilos, Panagiotis;Varela, Maria;Aytas, Ilknur;Gouliamos, Athanasios;Kelekis, Nikolaos
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.2717-2722
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    • 2013
  • Background: The objective of this research is the computed axial tomography (CT) imaging grading of radiation induced pneumonitis (RP) and its correlation with clinical and radiotherapeutic parameters. Materials and Methods: The chest CT films of 20 patients with non-small cell lung cancer who have undergone threedimensional conformal radiation therapy were reviewed. The proposed CT grading of RP is supported on solely radiological diagnosis criteria and distinguishes five grades. The manifestation of RP was also correlated with any positive pre-existing chronic obstructive pulmonary disease (COPD) history, smoking history, the FEV1 value, and the dosimetric variable V20. Results: The CT grading of RP was as follows: 3 patients (15%) presented with ground glass opacity (grade 1), 9 patients (45%) were classified as grade 2, 7 patients (35%) presented with focal consolidation, with or without elements of fibrosis (grade 3), and only one patient (5%) presented with opacity with accompanying atelectasis and loss of pulmonary volume (grade 4). Both univariate and multivariate analysis revealed as prognostic factors for the radiological grading of RP the reduction of FEV1 and the V20 (P=0.026 and P=0.003, respectively). There was also a significant (P<0.001) correlation of radiological grading of RP with FEV1 and V20 (spearman rho 0.92 and 0.93, respectively). Conclusions: The high correlation of the proposed radiological grading with the FEV1 and the V20 is giving a satisfactory clinical validity. Although the proposed grading scale seems relevant to clinical practice, further studies are needed for the confirmation of its validity and reliability.

Comparative Study of Gingival Changes in Cyclosporine-Induced Nephrotoxicity with Normal and Low Salt Diet (저염식으로 유도한 Cyclosporine 신독성 백서에서의 치은 변화)

  • Lim, Jae-Gye;Kim, Yong-Jin;Park, Yong-Hoon
    • Journal of Periodontal and Implant Science
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    • v.30 no.2
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    • pp.359-374
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    • 2000
  • Cyclosporine A(CsA) is a widely used immunosuppressant for transplant patients and is also used for the treatment of a wide variety of systemic diseases with immunologic disorders. However, its use is frequently limited because of complications such as nephrotoxicity or gingival hyperplasia. Although several hypotheses have been postulated for CsA-induced gingival hyperplasia, i.e. various cytokine effects of inflammatory cells, existence of plaque or CsA itself, but its pathogenesis is still unclear. For experimental chronic CsA toxicity, salt depletion has been shown to increased susceptibility of rodents to the effects of CsA, and this maneuver facilitates production of arteriolopathy and interstitial fibrosis in kidney that mimic the changes found in human. The purpose of this study was to evaluate pathogenesis of CsA-induced gingival hyperplasia by comparing changes between CsA administration groups of normal standard diet and those of low salt diet group. Specific pathogen-free, 20 to 25 days old(120 to 150 g), male Fisher-344 rats(KIST, Korea), 120 to 150g of body weight, were assigned to four groups of six animals each after one week of adaptation period for powder food. Group 1 received olive oil($300{\mu}l/g\;of\;diet$) with normal standard diet(0.4% of sodium)(NSD). Group 2 received CsA(Cypol-N, Jonggundang, Korea; $300{\mu}g/g\;of\;diet$) with normal standard diet(NSD+CsA). Group 3 received same amount of olive oil with low salt diet(0.05 % of sodium, Teklad Premier, U.S.A.)(LSD). Group 4 received same dose of CsA with low salt diet(LSD+CsA). Rats were pair fed and were sacrificed after six weeks. Renal histologic lesions associated with CsA, consisted of cortical interstitial fibrosis, tubular atrophy and hyalinization of arterioles and the impairment of renal function including increase of serum creatinine and decrease of glomerular filtration rate was more severe in low salt diet group. These were proved as the results of activated of renin-angiotensin system in the kidney by low salt condition. Meanwhile the degree of gingival hyperplasia at incisor and molar tooth was less severe in low salt diet group compared with normal sodium diet group. Hyperplastic gingiva showed mild epithelial hyperplasia and expanded underlyng stroma which consisted of matrix increasement, capillary proliferation and dilatation. While the number and the activation of fibroblasts were increased, inflammatory cells were rare in the stroma. The immunohistochemistry for TGF-${\beta}_1$ in the kidney and gingiva revealed stronger positive in LSD+CsA in kidney but in gingiva of NSD+CsA. These results suggested followings; Gingival hyperplasia can be developed without inflammatory cells infiltration and seemed not induced by CsA by itself. The major role for gingival hyperplasia by CsA would be the secondary effect of TGF-${\beta}$, which maybe upregulated by CsA administration. Low salt diet can attenuate this hyperplasia perhaps by decreasing the activation of $TGF-{\beta}$.

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An Introductory Research for Development of Soil Ecological Risk Assessment in Korea (토양생태 위해성평가 제도 국내 도입방안 연구)

  • An, Youn-Joo;Kim, Shin Woong;Moon, Jongmin;Jeong, Seung-Woo;Kim, Rog-Young;Yoon, Jeong-Ki;Kim, Tae-Seung
    • Journal of Korean Society of Environmental Engineers
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    • v.39 no.6
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    • pp.348-355
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    • 2017
  • Human activities have resulted in soil pollution problems to us. Human and ecological risk assessment have been suggested as an efficient environmental management strategy for protecting human and ecosystems from soil pollution. However, Korean environmental policy is currently focused on human protection, and fundamental researches for ecology protection are required for institutional frameworks. In this study, we developed a schematic frame of Korean soil ecological risk assessment, and suggested the basic information for its application. This study suggested a soil ecological risk assessment scheme consisting of 4 steps for derivation of Predicted-No-Effect-Concentration (PNEC): 1) ecotoxicity data collection and reliability determination, 2) data standardization, 3) evaluation of data completeness for PNEC calculation, and 4) determination of ecological-risk. The reliability determination of ecotoxicity data was performed using Reliability Index (RI), and the classification of domestic species, acute/chronic, toxicity endpoint, and soil properties was used for data cataloging. The PNEC calculation methodology was determined as low-reliability, middle-reliability, and high-reliability according to their quantitative and qualitative levels of ecotoxicity data. This study would be the introductory plan research for establishment of Korean soil ecological risk assessment, and it can be a fundamental framework to further develop guidelines of Korean environmental regulation.

Comparison between preoperative and postoperative concurrent chemoradiotherapy for rectal cancer: an institutional analysis

  • Lee, Jeong Won;Lee, Jong Hoon;Kim, Jun-Gi;Oh, Seong Taek;Chung, Hyuk Jun;Lee, Myung Ah;Chun, Hoo Geun;Jeong, Song Mi;Yoon, Sei Chul;Jang, Hong Seok
    • Radiation Oncology Journal
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    • v.31 no.3
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    • pp.155-161
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    • 2013
  • Purpose: To evaluate the treatment outcomes of preoperative versus postoperative concurrent chemoradiotherapy (CRT) on locally advanced rectal cancer. Materials and Methods: Medical data of 114 patients with locally advanced rectal cancer treated with CRT preoperatively (54 patients) or postoperatively (60 patients) from June 2003 to April 2011 was analyzed retrospectively. 5-Fluorouracil (5-FU) or a precursor of 5-FU-based concurrent CRT (median, 50.4 Gy) and total mesorectal excision were conducted for all patients. The median follow-up duration was 43 months (range, 16 to 118 months). The primary end point was disease-free survival (DFS). The secondary end points were overall survival (OS), locoregional control, toxicity, and sphincter preservation rate. Results: The 5-year DFS rate was 72.1% and 48.6% for the preoperative and postoperative CRT group, respectively (p = 0.05, the univariate analysis; p = 0.10, the multivariate analysis). The 5-year OS rate was not significantly different between the groups (76.2% vs. 69.0%, p = 0.23). The 5-year locoregional control rate was 85.2% and 84.7% for the preoperative and postoperative CRT groups (p = 0.98). The sphincter preservation rate of low-lying tumor showed significant difference between both groups (58.1% vs. 25.0%, p = 0.02). Pathologic tumor and nodal down-classification occurred after the preoperative CRT (53.7% and 77.8%, both p < 0.001). Acute and chronic toxicities were not significantly different between both groups (p=0.10 and p = 0.62, respectively). Conclusion: The results confirm that preoperative CRT can be advantageous for improving down-classification rate and the sphincter preservation rate of low-lying tumor in rectal cancer.