• Title/Summary/Keyword: Chronic Toxicity

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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.

Effect of Safflower and Safflower Seed Extract on Osteogenic Differentiation of MC3T3E1 Cells (홍화, 홍화씨 추출물이 MC3T3E1 세포의 골분화 과정에 미치는 영향)

  • Yu, Sung-ryul;Shin, Seon-mi
    • The Journal of Internal Korean Medicine
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    • v.36 no.4
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    • pp.518-526
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    • 2015
  • Objectives This study investigated the effect of purified safflower (Carthamus tinctorius Linne) and safflower seed (Carthamus tinctorius L. seed; CS) extract, using hot water and ethanol extract methods , on the osteogenic differentiation of MC3T3E1 cells.Methods The safflower and safflower seed were extracted with hot water and ethanol. The samples were concentrated by a rotary evaporator and then freeze-dried using a freeze-dryer. The MC3T3E1 cells were propagated and maintained in DMEM (Gibco) containing 10% FBS and a 1% antibiotic antimycotic solution. To induce osteogenic differentiation, the cells were treated for 14 days with DMEM with 10 mM β-glycerophosphate and 50 μM ascorbic acid. Extract doses were confirmed by the results of an MTT assay, and treatment of the extracts was performed in a differentiation medium every two days. The ALP staining and activity were tested after osteogenic differentiation for five days, and after 14 days, osteogenic differentiation was determined by alizarin red S staining. The mRNA expressions of osteogenic-related genes were quantified using quantitative real-time PCR.Results In the results of the MTT assay, all concentrations of safflower extracts had no toxicity in the MC3T3El cells. But in the groups of 100 ng/ml and 200 ng/ml concentrations of safflower seed extracts, the cell viability was significantly reduced by up to 40-50%. So we fixed the treatment concentration of the extract at 50 ng/ml. In the ALP and alizarin red S staining, all extract groups increased osteogenic differentiation compared with the control group. The water-safflower extract group showed the highest mRNA level of Alp, Runx2, and Dlx5 genes. The mRNA level of Ocn, an osteogenic gene related to late-stage differentiation, in the ethanol-safflower extract group increased the mineralization more significantly than in other groups.Conclusions These data suggest that the extract of safflower increases the osteoblastic differentiation activates of MC3T3E1 cells like the extract of safflower seed. The water-extract and ethanol-extract of safflower have effects on different stages of osteogenesis in MC3T3El. Not only safflower seed but also safflower will be useful therapeutic reagents for age-associated chronic diseases such as osteoporosis.

Neuroprotective Effects of Herbal Ethanol Extract from Gynostemma pentaphyllum on Dopamine Neurons in Rotenone- and MPTP-induced Animal Model of Parkinson's Disease (Rotenone- 및 MPTP-유도 파킨슨병 동물 모델에서 돌외 에탄올 추출물의 Dopamine 신경세포 보호작용)

  • Suh, Kwang Hoon;Choi, Hyun Sook;Shin, Kun Seong;Zhao, Ting Ting;Kim, Seung Hwan;Hwang, Bang Yeon;Lee, Chong Kil;Lee, Myung Koo
    • YAKHAK HOEJI
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    • v.57 no.2
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    • pp.77-86
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    • 2013
  • The neuroprotective effects of herbal ethanol extract (GP-EX) from Gynostemma pentaphyllum on dopamine neurons in animal model of Parkinson's disease (PD) were investigated. Rats and mice were administered with rotenone (2.5 mg/kg) for 28 days and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg) for 5 days for the PD models, respectively and the animals were simultaneously treated with GP-EX (30 mg/kg, daily). After preparing the PD models, the animals were also administered with L-DOPA (10 mg/kg) for 14 days with or without GP-EX treatment. Treatment with GP-EX (30 mg/kg) inhibited the rotenone- and MPTP-induced neurotoxic effects in dopamine neurons of rats or mice, which was determined by the numbers of tyrosine hydroxylase-immunohistochemical staining survival cells, as well as the levels of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid. GP-EX (30 mg/kg) also showed the protective effects on neurotoxicity which was induced by long-term administration of L-DOPA (10 mg/kg) in rotenone- and MPTP-induced animal model of PD. The used doses of GP-EX (30 mg/kg) did not produce any signs of toxicity, such as weight loss, diarrhea, or vomiting, in rats and mice during the treatment periods. These results suggest that GP-EX has the protective functions against chronic L-DOPA-induced neurotoxic reactions in dopamine neurons of rotenone- and MPTP-induced animal model of PD. Therefore, the natural GP-EX may be beneficial in the prevention of PD progress and L-DOPA-induced neurotoxicity in PD patients.

In vitro Inhibitory Effect of Aged Black Garlic Extract with Antioxidant Activity on MMP-2 and MMP-9 Related to Metastasis (In vitro에서 항산화 효능이 있는 흑마늘 추출물의 MMP-2 및 MMP-9에 대한 활성 억제효과)

  • Lee, Soo-Jin;Nam, Hyang;Kim, Moon-Moo;Jang, Ho-Jung;Park, Jung-Ae;Kim, Byung-Woo;Chung, Kyung-Tae
    • Journal of Life Science
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    • v.20 no.5
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    • pp.760-767
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    • 2010
  • The oxidative damage of lipids, protein, and DNA is known to be involved in not only chronic inflammations such as arthritis, hepatitis, nephritis, gastritis, colitis, and periodontitis but also metastasis. It has given impetus to searching for natural compounds without toxicity, which prevent the development of these diseases. The direct scavenging effects of aged black garlic extract (ABGE) were evaluated in vitro on DPPH radical, hydroxyl radical, hydrogen peroxide, and genomic DNA damage related to oxidative stress. Furthermore, its antioxidant effect on lipid peroxidation was investigated in human fibrosarcoma cells (HT1080), which were exposed to the hydroxyl radical generated by the Fenton reaction. It was observed that ABGE exhibited a greater inhibitory effect on hydrogen peroxide than other reactive oxygen species, and also blocked DNA oxidation and lipid peroxidation induced by the hydroxyl radical. The oxidative stress in live cells was also inhibited in the presence of ABGE. In addition, its inhibitory effects on the activity and expression of MMP-2 and -9 related to metastasis were determined using gelatin zymography and western blot. The data showed that it inhibited MMP-2 and -9 in PMA-stimulated HT1080 cells. Therefore, these results suggest that ABGE show potential as an excellent agent for prevention of metastasis related to oxidative stress.

Oxaliplatin-induced Peripheral Neuropathy in Patients with Advanced or Metastatic Gastric Cancer (진행성 또는 전이성 위암 환자에 있어서 Oxaliplatin 투여로 인한 말초신경통증 분석)

  • Park, Ae-Ryoung;Kim, Soon-Joo;Bang, Joon-Seok;La, Hyen-Oh
    • Korean Journal of Clinical Pharmacy
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    • v.19 no.1
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    • pp.18-22
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    • 2009
  • Oxaliplatin is a tolerable and effective drug of choice in the treatment of advanced or metastatic gastric cancer. However, it has many dose-limiting neurotoxicities. This study was performed to assess the incidence and types of oxaliplatin-related neurotoxicities. Sixty-four patients receiving oxaliplatin-involved regimen as salvage therapy on metastatic gastric cancer or as the first-line therapy on advanced gastric cancer were evaluated during the period between September 1, 2006 and February 29, 2008. The patients were treated with oxaliplatin 100 $mg/m^2$ and leucovorin 100 $mg/m^2$ simultaneously as 2-hour-lasting infusion on Day-1 followed by 5-FU 1200 $mg/m^2$ as a 22-hour-lasting continuous infusion both on Day-1 and Day-2 by every other week. We developed questionnaires to evaluate patient-recognized neurotoxic symptoms rather than the observer-described events. Surveys were completed at bedside or via telephone interview. Acute and chronic neurotoxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC, version 3) as well as the Oxaliplatin-specific Neurotoxicity Scale. The Grade-3 neuropathy was reported in 19% of the patients (n=12) and grade-1/2 neuropathy occurred in 70% (n=45). The most common symptom was cold-related dysesthesia (83%) regarded as nociperception by the patients. Some patients (19%) experienced functional impairment affecting activities of daily living such as writing, buttoning, and walking. Even though 74% of the patients (42/57) were prescribed with gabapentin to reduce these peripheral symptoms, it did not appear to derive any benefit from this medication. It is suggested that notify the patients about their oxaliplatin-associated, debilitating symptoms, and educate them any self-care strategy at the initiating phase of the chemotherapy. Moreover, it needs to design the intervention studies regarding the prevention and management of the peripheral neuropathy.

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Acute Cytotoxicity Testing of Polyhexamethylene-biguanide (PHMG) and Epigallocatechin-gallate (EGCG) Mixture on the Cultured Human Corneal Epithelial Cell (보존제 PHMB(polyhexamethylene biguanide)-EGCG(epigallocatechin gallate) 혼합물의 각막상피세포 급성독성 평가)

  • Kim, Nam-youl;Lee, Koon-Ja
    • The Korean Journal of Vision Science
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    • v.20 no.4
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    • pp.531-541
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    • 2018
  • Purpose : To evaluate the acute cytotoxic effect of polyhexamethylene biguanide (PHMB), epigallocatechin gallate (EGCG) and PHMB/EGCG mixture on the cultured human corneal epithelial cell (HCEpiC). Methods : HCEpiCs were cultured in the media of HCEpiC containing 0.00001~0.005% PHMB, 0.001~5% EGCG and 0.00005% PHMB/0.05% EGCG mixture respectively for 30, 60, 120 and 240 min. Cultured HCEpiCs were fixed and stained with Draq5 and cell viability and apoptosis were evaluated using confocal microscope and ImageXpress $Ultra^{TM}$. Results : Cultured HCEpiC did not show cytotoxic effect at below 0.00005% PHMB and below 0.05% EGCG concentration. In the media containing 0.00005% PHMB/0.05% EGCG, acute cytototoxic effect was not found, whereas damaged HCEpiCS were increased and survival cells were decreased in the media incubated for 240 min. Conclusion : The mixture of 0.00005% PHMB/0.05% EGCG showed non acute cytotoxic effect on the cultured HCEpiCs, however it is needed to investigate its chronic cytotoxic effect.