• Title/Summary/Keyword: human disease

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An International Collaborative Program To Discover New Drugs from Tropical Biodiversity of Vietnam and Laos

  • Soejarto, Djaja D.;Pezzuto, John M.;Fong, Harry H.S.;Tan, Ghee Teng;Zhang, Hong Jie;Tamez, Pamela;Aydogmus, Zeynep;Chien, Nguyen Quyet;Franzblau, Scott G.;Gyllenhaal, Charlotte;Regalado, Jacinto C.;Hung, Nguyen Van;Hoang, Vu Dinh;Hiep, Nguyen Tien;Xuan, Le Thi;Hai, Nong Van;Cuong, Nguyen Manh;Bich, Truong Quang;Loc, Phan Ke;Vu, Bui Minh;Southavong, Boun Hoong
    • Natural Product Sciences
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    • v.8 no.1
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    • pp.1-15
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    • 2002
  • An International Cooperative Biodiversity Group (ICBG) program based at the University of Illinois at Chicago initiated its activities in 1998, with the following specific objectives: (a) inventory and conservation of of plants of Cuc Phuong National Park in Vietnam and of medicinal plants of Laos; (b) drug discovery (and development) based on plants of Vietnam and Laos; and (c) economic development of communities participating in the ICBG project both in Vietnam and Laos. Member-institutions and an industrial partner of this ICBG are bound by a Memorandum of Agreement that recognizes property and intellectual property rights, prior informed consent for access to genetic resources and to indigenous knowledge, the sharing of benefits that may arise from the drug discovery effort, and the provision of short-term and long-term benefits to host country institutions and communities. The drug discovery effort is targeted to the search for agents for therapies against malaria (antimalarial assay of plant extracts, using Plasmodium falciparum clones), AIDS (anti-HIV-l activity using HOG.R5 reporter cell line (through transactivation of the green fluorescent protein/GFP gene), cancer (screening of plant extracts in 6 human tumor cell lines - KB, Col-2, LU-l, LNCaP, HUVEC, hTert-RPEl), tuberculosis (screening of extracts in the microplate Alamar Blue assay against Mycobacterium tuberculosis $H_{37}Ra\;and\;H_{37}Rv),$ all performed at UIC, and CNS-related diseases (with special focus on Alzheimer's disease, pain and rheumatoid arthritis, and asthma), peformed at Glaxo Smith Kline (UK). Source plants were selected based on two approaches: biodiversity-based (plants of Cuc Phuong National Park) and ethnobotany-based (medicinal plants of Cuc Phuong National Park in Vietnam and medicinal plants of Laos). At mc, as of July, 2001, active leads had been identified in the anti-HIV, anticancer, antimalarial, and anti- TB assay, after the screening of more than 800 extracts. At least 25 biologically active compounds have been isolated, 13 of which are new with anti-HIV activity, and 3 also new with antimalarial activity. At GSK of 21 plant samples with a history of use to treat CNS-related diseases tested to date, a number showed activity against one or more of the CNS assay targets used, but no new compounds have been isolated. The results of the drug discovery effort to date indicate that tropical plant diversity of Vietnam and Laos unquestionably harbors biologically active chemical entities, which, through further research, may eventually yield candidates for drug development. Although the substantial monetary benefit of the drug discovery process (royalties) is a long way off, the UIC ICBG program provides direct and real-term benefits to host country institutions and communities.

The Monitoring of Heavy Metals in Human Bloods of Middle School Students (중학생의 혈액 중 중금속 모니터링)

  • Park Hee Ra;Kim Meehye;Kwun Ki-Sung;Kim Soon Ki;Heo Su-Jeong;Kim Kwang_Jin;Yum Tae-Kyung;Choi Kwang Sik;Kim Soo Yeon
    • Journal of Food Hygiene and Safety
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    • v.20 no.2
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    • pp.83-88
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    • 2005
  • This study was conducted to estimate the contents of heavy metals including lead, cadmium, zinc, copper as well as iron status(serum iron, total iron binding capacity, feritin etc)in blood samples of middle school students(n=300). The contents of heavy metals were determined using the GF-AAS (Graphite furnace Atomic Absorption Spectrophotometer). The microwave digestion method and dilution method were compared. The dilution method showed the better recovery and detection limit than microwave digestion method. The values of toxic metals in whloe blood of boys & girls were 3.46 & 3.05 for Pb,0.063 & 0.065 for Cd respectively (ug/dL). Also the values of trace metals in serum of boys & girls were 105.9 & 92.6 for Zn, 98.3 & 99.0 for Cu respectively (ug/dL). The prevalence of iron deficiency was $7.5\%$ in 146 boys and $14.3\%$ in 156 girls. The mean values of lead in girls were higher in iron deficiency, iron deficiency anemia and anemia groups than normal group. The mean values of lead and zinc were higher in boys compared to those in girls(P<0.05), the mean values of cadmium and copper in boys were similar to those in girls. Our results of toxic metals such as Pb & Cd showed lower to CDC's(Centers for Disease Control) blood lead levels of concern for children, 10 ug/dL.

The Immunohistochemical Analysis for the Expression of Survivin, HSP, and Bcl-2 in Non-small Cell Lung Carcinoma (비소세포폐암에서 Survivin, HSP 및 Bcl-2 발현에 관한 면역조직화학적 분석)

  • Hong, Hyun-Ju;Hong, Seok-Gyun;Lee, Kye-Young;Kim, Woo-Ho;Lee, Choon-Taek;Yoo, Chul-Gyu;Han, Sung-Koo;Shim, Young-Soo;Kim, Young-Whan
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.5
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    • pp.441-452
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    • 2002
  • Background : Anti-apoptotic proteins may be involved in tumor development, progression and the response to treatment, Bcl-2 is by far the most studied anti-apoptotic protein. A novel inhibitor of apoptosis, designated survivin, and the heat shock proteins (HSPs) have recently been found in many human cancers. Immunohistochemical methods were used to determine the expression level of survivin, HSP70 and bcl-2 in non-small cell lung cancer (NSCLC) to evaluate their clinical significance. Materials and Methods : Tissue array slides were obtained from 99 surgically resected NSCLCs. Immunohistochemical staining was performed by an immuno-peroxidase technique using an avidin-biotinylated horseradish peroxidase complex. Anti-survivin rabbit polyclonal antibodies, anti-HSP70 mouse monoclonal antibodies and anti-bcl-2 mouse monoclonal antibodies were used as the primary antibodies. Results : Positive staining of survivin was detected in 33.3% of the cases. Survivin positivity is associated with to females and recurrence. A nonstatistically significant trend toward increased survivin expression was observed in non-smokers, and its expression inversely correlated with the number of cigarettes smoked in smokers. HSP70 was detected in 84.8% but this did not correlated with the clinicopathologic characteristics. Bcl-2 was detected in 18.2% and its expression correlated to tumor recurrence. No significant difference in the median survival time was noted in a comparison of all cases with survivin expression and those without. There was no association between HSP70 or bcl-2 expression and survival. Conclusion : Survivin expression was significantly associated with females and tumor recurrence. In addition its expression was inversely associated with the number of cigarettes smoked. However, HSP70 and bcl-2 expression were not associated with the clinical parameters or survival. This suggests that measuring the survivin levels may be useful in identifying patients at high risk for disease recurrence. Therefore, survivin might be a new diagnostic/therapeutic target in cancer.

A Low-Dose High-Resolution SPECT System with CdTe for Small-Animal Imaging Applications: A GATE Simulation Study (GATE 시뮬레이션을 통한 고해상도 저선량용 소동물 영상화를 위한 CdTe 검출기 기반의 SPECT 기기 연구)

  • Park, Su-Jin;Yu, A Ram;Kim, Yeseul;Lee, Young-Jin;Kim, Hee-Joung
    • Progress in Medical Physics
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    • v.24 no.3
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    • pp.162-170
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    • 2013
  • Dedicated single-photon emission computed tomography (SPECT) systems based on pixelated semiconductors are being developed for studying small animal models of human disease. To clarify the possibility of using a SPECT system with CdTe for a high resolution low-dose small animal imaging, we compared the quality of reconstructed images from pixelated CdTe detector to those from a small SPECT system with NaI(Tl). The CdTe detector was $44.8{\times}44.8$ mm and the pixels were $0.35{\times}0.35{\times}5$ mm. The intrinsic resolution of the detector was 0.35 mm, which is equal to the pixel size. GATE simulations were performed to assess the image quality of both SPECT systems. The spatial resolutions and sensitivities for both systems were evaluated using a 10 MBq $^{99m}Tc$ point source. The quantitative comparison with different injected dose was performed using a voxelized MOBY phantom, and the absorbed doses for each organ were evaluated. The spatial resolution of the SPECT with NaI(Tl) was about 1.54 mm FWHM, while that of the SPECT with a CdTe detector was about 1.32 mm FWHM at 30 mm. The sensitivity of NaI(Tl) based SPECT was 83 cps/MBq, while that of the CdTe detector based SPECT was 116 cps/MBq at 30 mm. The image statistics were evaluated by calculating the CNR of the image from both systems. When the injected activity for the striatum in the mouse brain was 160 Bq/voxel, the CNR of CdTe based SPECT was 2.30 while that of NaI(Tl) based SPECT was 1.85. The CNR of SPECT with CdTe was overall higher than that of the NaI(Tl) based SPECT. In addition, the absorbed dose was higher from SPECT with CdTe than those from NaI(Tl) based SPECT to acquire the same quantitative values. Our simulation results indicated that the SPECT with CdTe detector showed overall high performance compared to the SPECT with NaI(Tl). Even though the validation study is needed, the SPECT system with CdTe detector appeared to be feasible for high resolution low-dose small animal imaging.

Fatty acid analysis and regulatory effects of citron (Citrus junos Sieb. ex TANAKA) seed oil on nitric oxide production, lipid accumulation, and leptin secretion (유자씨유의 지방산분석 및 Nitric Oxide 생성, 지방축적능, 렙틴분비 조절효과)

  • Kim, Tae Woo;Kim, Kyoung Kon;Kang, Yun Hwan;Kim, Dae Jung;Choe, Myeon
    • Journal of Nutrition and Health
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    • v.47 no.4
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    • pp.221-228
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    • 2014
  • Purpose: Citron seed oil (CSO) has been reported to have high antioxidant activity. However, the composition and other biologically activities of CSO have not been reported. In this study, we confirmed the fatty acid composition of CSO, which may be beneficial to vascular disease and obesity. Methods: We investigated the oil composition of CSO using gas chromatography coupled with mass spectrometry (GC-MS) analysis, and cytotoxicity was confirmed by Cell Counting Kit-8 (CCK-8) assay. Nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) was measured using Griess reagent, and lipid accumulation and leptin secretion in 3T3-L1 cells were measured by Oil-Red O staining and commercial ELISA kit, respectively. Results: GC-MS analysis indicated that CSO contains several components, including linoleic acid, oleic acid, palmitic acid, stearic acid, linolenic acid, palmitoleic acid, and arachidic acid. In physiological activity analysis, CSO did not induce cytotoxic effects in HUVECs and 3T3-L1 cells. Further, CSO significantly induced nitric oxide and leptin secretion as well as inhibited lipid accumulation. Conclusion: CSO increased NO release, inhibited lipid accumulation, and induced leptin secretion, suggesting it may be useful for the management of vessels and weight gain. Although further studies are required to investigate the safety and mechanism of action of CSO, our results show that the composition and physiological activity of CSO are sufficient for its use as functional edible oil.

The Effect of Postnatal Dexamethasone Treatment on Hypoxic-Ischemic Brain Injury in Neonatal Rats (신생쥐의 저산소성 허혈성 뇌손상에서 손상 후 덱사메타손의 투여 효과)

  • Park, Chang Ro;Park, Kyung Pil;Kim, Heng Mi;Sohn, Yoon Kyung
    • Clinical and Experimental Pediatrics
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    • v.46 no.10
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    • pp.989-995
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    • 2003
  • Purpose : Dexamethasone is frequently administered to prevent or treat chronic lung disease in human neonates who are also prone to hypoxic-ischemic(HI) insults. Recently, meta-analysis of the follow-up studies reveals a significantly increased odd ratio for the occurrence of cerebral palsy or an abnormal neurologic outcome, and there is conflicting evidence regarding the impact of dexamethasone exposure on HI brain injury. This study was conducted to explore the effect of post-HI dexamethasone administration on neuronal injury in neonatal rats. Methods : HI was produced in seven-day-old rats by right carotid artery ligation followed by two hours of 8% oxygen exposure. At the end of HI, the animals were injected intraperitoneally either with dexamethasone(0.5 mg/kg) or saline. Neuronal injury was assessed seven days after the HI by the area of infarction, TUNEL reactivity, Bcl-2 and Bax expression in brain. Results : Post-insult dexamethasone administration resulted in reduction of weight gain and a higher mortality rate during seven days after HI. Dexamethasone treatment revealed no effect on the size of brain infarction induced by HI. Bax protein expression increased in dexamethasone treated brain but Bcl-2 protein expression and TUNEL reactivity revealed no significant differences between dexamethasone treated and non treated brain. Increased Bax protein expression suggest upregulation of the apoptosis by dexamethasone. Conclusion : The result suggests the adverse role of Post-HI administration of dexamethasone in neonatal HI.

Association of HLA-G gene promoter haplotype with childhood IgA nephropathy in the Korean population (한국인에서의 소아 IgA 신병증과 HLA-G유전자의 promoter haplotype과의 관계)

  • Jung, Hwan-Hee;Hahn, Won-Ho;Cho, Byoung-Soo;Kim, Sung-Do
    • Clinical and Experimental Pediatrics
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    • v.53 no.4
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    • pp.548-553
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    • 2010
  • Purpose : IgA nephropathy (IgAN) is the most commonly occurring form of chronic glomerulonephritis in pediatric cases. Human leukocyte antigen (HLA) genes have been implicated in various inflammatory and autoimmune diseases. The present study was conducted to investigate the association between 2 single nucleotide polymorphisms (SNPs) of the HLA-G gene and childhood IgAN. Methods : The authors analyzed and compared $HLA-G$ gene SNPs (rs1736936 and rs2735022) in 174 patients with childhood IgAN and in 438 healthy controls. In addition, IgAN patients were dichotomized and compared with respect to proteinuria (< and >$4mg/m^2/hour$), the presence or absence of podocyte foot process effacement, and the presence of pathologically early and advanced disease markers such as interstitial fibrosis, tubular atrophy, or global sclerosis. Results : No significant SNP frequency differences were observed for the $HLA-G$ gene between IgAN patients and the control group. Moreover, no significantly associated SNP was observed with the presence of proteinuria, podocyte foot process effacement, or pathologically advanced markers. However, the haplotype, composed of rs1736936 and rs2735022, showed a significant association with the susceptibility to develop childhood IgAN (haplotype T/C: dominant model, $P$=0.049; haplotype C/T: recessive model, $P$=0.030). Conclusion : Our results indicate that rs1736936 and rs2735022 as the $HLA-G$ gene promoter haplotype might be associated with the susceptibility to develop childhood IgAN in the Korean population.

Clinical effects of combination anorganic bovine-derived hydroxyapatite matrix(ABM)/cell binding peptide (P-15) in periodontal intrabony defects (치주 골내낭에서 anorganic bovine-derived hydroxyapatite matrix(ABM)/cell binding peptide(P-15)의 임상적효과)

  • Won, Mi-Sook;Paik, Jeong-Won;Kim, Chang-Sung;Cho, Kyoo-Sung;Chai, Jung-Kiu;Kim, Chong-Kwan;Choi, Seong-Ho
    • Journal of Periodontal and Implant Science
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    • v.32 no.3
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    • pp.565-576
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    • 2002
  • The ultimate goal of periodontal therapy is the regeneration of periodontal tissue which has been lost due to destructive periodontal disease. To achieve periodontal regeneration, various kinds of methods have been investigated and developed, including guided tissue regeneration and bone graft. Bone graft can be catagorized into autografts, allografts, xenografts, bone substitutes. And materials of all types have different biological activity and the capacity for periodontal regeneration, but ideal graft material has not been developed that fits all the requirement of ideal bone graft material. Intensive research is underway to identity, purify, synthesize a variety biologic modulators that may enhance wound healing and regeneration of lost tissues in periodontal therapy. The present study evaluates the effects of ABM/P-15 on the periodontal regeneration in intrabony defects of human. We used thirty four 2-wall or 3-wall osseous defects in premolars and molars of chronic peridontitis patient that have more than 5mm pockets and more than 3mm in intrabony defect. 12 negative control group underwent flap procedure only, 11 positive control group received DFDBA graft with flap procedure, and 11 experimental group received ABM/P-15 graft with flap procedure. The changes of probing pocket depth, loss of attachment and bone probing depth following 6months after treatment revealed the following results: 1. The changes of probing pocket depth showed a statistically significant decrease between after scaling and 6months after treatment in negative control(2.0${\pm}$0.9mm), positive control(3.0${\pm}$0.9mm), and experimental group (3.4${\pm}$1.5mm) (P<0.01). Significantly more reduction was seen in experimental group compared to negative control group (P<0.05). 2. The changes of loss of attachment showed a statistically significant decrease between after scaling and 6months after treatment in positive control(2.0${\pm}$0.6mm), and experimental group (2.2${\pm}$l.0mm) except negative control group(0.1${\pm}$0.7mm) (P<0.01). Significantly more reduction was seen in both experimental and positive control group compared to negative control group(P<0.05). 3. The changes of bone probing depth showed a statistically significant decrease between after scaling and 6months after treatment in positive control(2.7${\pm}$l.0mm), and experimental group (3.4${\pm}$1.3mm) except negative control(0.l${\pm}$0.9mm) (9<0.01). Significantly more reduction was seen in both experimental and positive control group compared to negative control group (P<0.05). The results suggest that the use of ABM/P-15 in the treatment of periodontal intrabony defects can reduce loss of attachment and bone probing depth more than flap operation only. It suggests that ABM/P-15 may be an effective bone graft material for the regeneration of periodontal tissue in intrabony defects.

Monitoring Ground-level SO2 Concentrations Based on a Stacking Ensemble Approach Using Satellite Data and Numerical Models (위성 자료와 수치모델 자료를 활용한 스태킹 앙상블 기반 SO2 지상농도 추정)

  • Choi, Hyunyoung;Kang, Yoojin;Im, Jungho;Shin, Minso;Park, Seohui;Kim, Sang-Min
    • Korean Journal of Remote Sensing
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    • v.36 no.5_3
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    • pp.1053-1066
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    • 2020
  • Sulfur dioxide (SO2) is primarily released through industrial, residential, and transportation activities, and creates secondary air pollutants through chemical reactions in the atmosphere. Long-term exposure to SO2 can result in a negative effect on the human body causing respiratory or cardiovascular disease, which makes the effective and continuous monitoring of SO2 crucial. In South Korea, SO2 monitoring at ground stations has been performed, but this does not provide spatially continuous information of SO2 concentrations. Thus, this research estimated spatially continuous ground-level SO2 concentrations at 1 km resolution over South Korea through the synergistic use of satellite data and numerical models. A stacking ensemble approach, fusing multiple machine learning algorithms at two levels (i.e., base and meta), was adopted for ground-level SO2 estimation using data from January 2015 to April 2019. Random forest and extreme gradient boosting were used as based models and multiple linear regression was adopted for the meta-model. The cross-validation results showed that the meta-model produced the improved performance by 25% compared to the base models, resulting in the correlation coefficient of 0.48 and root-mean-square-error of 0.0032 ppm. In addition, the temporal transferability of the approach was evaluated for one-year data which were not used in the model development. The spatial distribution of ground-level SO2 concentrations based on the proposed model agreed with the general seasonality of SO2 and the temporal patterns of emission sources.

Microbial Risk Assessment in Treated Wastewater Irrigation on Paddy Rice Plot (하수처리수를 관개한 후 벼재배 시험구에 대한 미생물 위해성 평가)

  • Jung, Kwang-Wook;An, Youn-Joo;Jang, Jae-Ho;Jeon, Ji-Hong;Yoon, Chun-Gyeong
    • Korean Journal of Ecology and Environment
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    • v.38 no.2 s.112
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    • pp.225-236
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    • 2005
  • The protection of public health In wastewater reclamation and reuse is one of the most important issues. Monitoring data of Escherichia coli were collected from paddy rice plots in 2003 and 2004 experiments. Five treatments were used and each one was triplicated to evaluate the changes of E. coli: surface water, biofilter effluent (secondary level), UV-disinfected water and pond treatment. Microbial risk was quantified to assess human health risk by exposure to E. coli in paddy rice plots, which were irrigated with reclaimed wastewater. Beta-Poisson model was used to estimate the microbial risk of pathogen ingestion that may occur to farmer and neighbor children. Monte-Carlo analysis (10,000 trials) was used to estimate the risk characterization of uncertainty. In the following analysis, two scenarios were related to the reduction of risk against direct ingestion and exposure times. Scenarios A and B were assumed that the risk was 1,000 and 10,000 times lower than direct ingestion.'Golfers were assumed to be 0.001 L of reclaimed water by contact with balls and their cloths. Opportunity of contact in paddy rice field with pathogens was more frequent than handing golf balls, because of agricultural activity was practiced in ponded water in paddy rice culture. As a result of microbial risk assessment using total data of experimental period, risk value of E. coli in 2003 and 2004 experiment ranged from $10^{-5}$ to $10^{-8}$ and $10^{-4}$ to $10^{-8}$, respectively. The risk values in biofilter effluent irrigation was the highest, which is $10^{-4}$ in 2003 and $10^{-5}$ in 2004 experiments with scenario A. Ranges of $10^{-6}$ to $10^{-8}$ were considered at reasonable levels of risk for communicable disease transmission from environmental exposure and the risk value above $10^{-4}$ was considered to be attributable to the risk of infection. Irrigation with UV-disinfected water in the paddy field during the agricultural Period showed significantly lower microbial risk than others, and their levels of risk value were within the range of actual paddy rice field with surface water.