• Title/Summary/Keyword: Biological safety

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The evaluation on the biological safety of diagnostic ultrasound using radiation-induced apoptosis in the external granular layer of mouse cerebellum (마우스 소뇌과립층의 apoptosis를 지표로 한 진단용 초음파의 안전성 검증)

  • Oh, Heon;Lee, Song-eun;Yang, Jung-ah;Jo, Sung-kee;Chung, Chi-young;Son, Chang-ho;Kim, Sung-ho
    • Korean Journal of Veterinary Research
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    • v.39 no.3
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    • pp.628-634
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    • 1999
  • We have studied, by a nonisotopic in situ end-labeling(ISEL) technique, frequency of apoptosis in the external granular layer(EGL) of the cerebellum of immature mice by ${\gamma}$-rays irradiation from $^{60}Co$ or diagnostic ultrasound exposure. The total number of normal cells and cells showing morphological features of apoptosis were counted. The frequency of apoptotic cells was expressed as a percentage of the total number of cells in EGL. The extent of changes following 200 cGy(1090 cGy/min) was studied at 2, 4, 6, 8, 12, or 24 hours after exposure. The maximal frequency was found 6~8 hours after exposure. The immature mice that received 18, 36, 54, 108, 198, 396 cGy of ${\gamma}$-rays or diagnostic ultrasound(7.5MHz, 4.2mW, $I_{SPTA}=7.9mW/cm^2$, $I_{SPTA}=114.3W/cm^2$) for 10 or 30 minutes were examined 6 hours after irradiation. Measurements performed after ${\gamma}$-ray irradiation showed a dose-related increase in apoptotic cells in each of the mice studied. The dose-response curves were analyzed by a linear-quadratic model ; frequency of apoptotic cell in the EGL was y = $(0.1349{\pm}0.01175)D$+$(-0.0001522{\pm}0.0000334)D^2$+0.048($r^2$ = 0.981, D = dose in cGy). In the experiment of ultrasound exposure, the frequency of apoptotic cell was $0.106{\pm}0.130$(10 minutes exposure) and $0.167{\pm}0.220$(30 minutes exposure). We estimated the relative dose of the yield from the experiment with ultrasound by substituting the yield from ultrasound exposure into the curve from the ${\gamma}$-irradiation. The relative dose of ultrasound exposure compared with ${\gamma}$-irradiation were 0.432 cGy(10 minutes exposure) and 0.885 cGy(30 minutes exposure). We have found that there is no evidence to indicate that diagnostic ultrasound involves a significant risk.

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Implementation on the evolutionary machine learning approaches for streamflow forecasting: case study in the Seybous River, Algeria (유출예측을 위한 진화적 기계학습 접근법의 구현: 알제리 세이보스 하천의 사례연구)

  • Zakhrouf, Mousaab;Bouchelkia, Hamid;Stamboul, Madani;Kim, Sungwon;Singh, Vijay P.
    • Journal of Korea Water Resources Association
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    • v.53 no.6
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    • pp.395-408
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    • 2020
  • This paper aims to develop and apply three different machine learning approaches (i.e., artificial neural networks (ANN), adaptive neuro-fuzzy inference systems (ANFIS), and wavelet-based neural networks (WNN)) combined with an evolutionary optimization algorithm and the k-fold cross validation for multi-step (days) streamflow forecasting at the catchment located in Algeria, North Africa. The ANN and ANFIS models yielded similar performances, based on four different statistical indices (i.e., root mean squared error (RMSE), Nash-Sutcliffe efficiency (NSE), correlation coefficient (R), and peak flow criteria (PFC)) for training and testing phases. The values of RMSE and PFC for the WNN model (e.g., RMSE = 8.590 ㎥/sec, PFC = 0.252 for (t+1) day, testing phase) were lower than those of ANN (e.g., RMSE = 19.120 ㎥/sec, PFC = 0.446 for (t+1) day, testing phase) and ANFIS (e.g., RMSE = 18.520 ㎥/sec, PFC = 0.444 for (t+1) day, testing phase) models, while the values of NSE and R for WNN model were higher than those of ANNs and ANFIS models. Therefore, the new approach can be a robust tool for multi-step (days) streamflow forecasting in the Seybous River, Algeria.

Induction of Cell Cycle Arrest at G2/M phase by Ethanol Extract of Scutellaria baicalensis in Human Renal Cell Carcinoma Caki-1 Cells (황금 에탄올 추출물에 의한 인간 신장암 세포주 Caki-1의 G2/M arrest 유발)

  • Park, Dong-Il;Jeong, Jin-Woo;Park, Cheol;Hong, Su-Hyun;Shin, Soon-Shik;Choi, Sung-Hyun;Choi, Yung-Hyun
    • Herbal Formula Science
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    • v.23 no.2
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    • pp.199-208
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    • 2015
  • Objectives : In the present study, we investigated the effects of ethanol extract of Scutellaria baicalensis (EESB) on the progression of cell cycle in human renal cell carcinoma Caki-1 cells. Methods : The effects of EESB on cell growth and apoptosis induction were evaluated by trypan blue dye exclusion assay and flow cytometry, respectively. The mRNA and protein levels were determined by Western blot analysis and reverse transcription-polymerase chain reaction, respectively. Results : It was found that EESB treatment on Caki-1 cells resulted in a dose-dependent inhibition of cell growth and induced apoptotic cell death as detected by Annexin V-FITC staining. The flow cytometric analysis indicated that EESB resulted in G2/M arrest in cell cycle progression which was associated with the down-regulation of cyclin A expression. Our results also revealed that treatment with EESB increased the mRNA and proteins expression of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1), without any noticeable changes in cyclin B1, Cdk2 and Cdc2. In addition, the incubation of cells with EESB resulted in a significant increase in the binding of p21 and Cdk2 and Cdc2. These findings suggest that EESB-induced G2/M arrest and apoptosis in Caki-1 cells is mediated through the p53-mediated upregulation of Cdk inhibitor p21. Conclusions : Taken together, these findings suggest that EESB may be a potential chemotherapeutic agent and further studies will be needed to identify the biological active compounds that confer the anti-cancer activity of S. baicalensis.

Evaluation of a Sample-Pooling Technique in Estimating Bioavailability of a Compound for High-Throughput Lead Optimazation (혈장 시료 풀링을 통한 신약 후보물질의 흡수율 고효율 검색기법의 평가)

  • Yi, In-Kyong;Kuh, Hyo-Jeong;Chung, Suk-Jae;Lee, Min-Haw;Shim, Chang-Koo
    • Journal of Pharmaceutical Investigation
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    • v.30 no.3
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    • pp.191-199
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    • 2000
  • Genomics is providing targets faster than we can validate them and combinatorial chemistry is providing new chemical entities faster than we can screen them. Historically, the drug discovery cascade has been established as a sequential process initiated with a potency screening against a selected biological target. In this sequential process, pharmacokinetics was often regarded as a low-throughput activity. Typically, limited pharmacokinetics studies would be conducted prior to acceptance of a compound for safety evaluation and, as a result, compounds often failed to reach a clinical testing due to unfavorable pharmacokinetic characteristics. A new paradigm in drug discovery has emerged in which the entire sample collection is rapidly screened using robotized high-throughput assays at the outset of the program. Higher-throughput pharmacokinetics (HTPK) is being achieved through introduction of new techniques, including automation for sample preparation and new experimental approaches. A number of in vitro and in vivo methods are being developed for the HTPK. In vitro studies, in which many cell lines are used to screen absorption and metabolism, are generally faster than in vivo screening, and, in this sense, in vitro screening is often considered as a real HTPK. Despite the elegance of the in vitro models, however, in vivo screenings are always essential for the final confirmation. Among these in vivo methods, cassette dosing technique, is believed the methods that is applicable in the screening of pharmacokinetics of many compounds at a time. The widespread use of liquid chromatography (LC) interfaced to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) allowed the feasibility of the cassette dosing technique. Another approach to increase the throughput of in vivo screening of pharmacokinetics is to reduce the number of sample analysis. Two common approaches are used for this purpose. First, samples from identical study designs but that contain different drug candidate can be pooled to produce single set of samples, thus, reducing sample to be analyzed. Second, for a single test compound, serial plasma samples can be pooled to produce a single composite sample for analysis. In this review, we validated the issue whether the second method can be applied to practical screening of in vivo pharmacokinetics using data from seven of our previous bioequivalence studies. For a given drug, equally spaced serial plasma samples were pooled to achieve a 'Pooled Concentration' for the drug. An area under the plasma drug concentration-time curve (AUC) was then calculated theoretically using the pooled concentration and the predicted AUC value was statistically compared with the traditionally calculated AUC value. The comparison revealed that the sample pooling method generated reasonably accurate AUC values when compared with those obtained by the traditional approach. It is especially noteworthy that the accuracy was obtained by the analysis of only one sample instead of analyses of a number of samples that necessitates a significant man-power and time. Thus, we propose the sample pooling method as an alternative to in vivo pharmacokinetic approach in the selection potential lead(s) from combinatorial libraries.

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Development of real-time PCR for rapid detection of Mycobacterium bovis DNA in cattle lymph nodes and differentiation of M. bovis and M. tuberculosis (소 림프절에서 Mycobacterium bovis DNA의 신속 검출과 M. bovis와 M. tuberculosis 감별을 위한 real-time PCR 개발)

  • Koh, Ba-Ra-Da;Jang, Young-Boo;Ku, Bok-Kyung;Cho, Ho-Seong;Bae, Seong-Yeol;Na, Ho-Myung;Park, Seong-Do;Kim, Yong-Hwan;Mun, Yong-Un
    • Korean Journal of Veterinary Service
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    • v.34 no.4
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    • pp.321-331
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    • 2011
  • Mycobacterium bovis, a member of the M. tuberculosis complex (MTC), is the causative agent of bovine tuberculosis. Detection of M. bovis and M. tuberculosis using conventional culture- and biochemical-based assays is time-consuming. Therefore, a simple and sensitive molecular assay for rapid detection would be of great help in specific situations such as faster diagnosis of bovine tuberculosis (bTB) infection in the abattoirs. We developed a novel multiplex real-time PCR assay which was applied directly to biological samples with evidence of bTB and it was allowed to differentiate between M. bovis and M. tuberculosis. The primers and TaqMan probes were designed to target the IS1081 gene, the multi-copy insertion element in the MTC and the 12.7-kb fragment which presents in M. tuberculosis, not in the M. bovis genome. The assay was optimized and validated by testing 10 species of mycobacteria including M. bovis and M. tuberculosis, and 10 other bacterial species such as Escherichia coli, and cattle lymph nodes (n=113). The tests identified 96.4% (27/28) as M. bovis from the MTC-positive bTB samples using conventional PCR for specific insertion elements IS1081. And MTC-negative bTB samples (n=85) were tested using conventional PCR and the real-time PCR. When comparative analyses were conducted on all bovine samples, using conventional PCR as the gold standard, the relative accuracy of real-time PCR was 99.1%, the relative specificity was 100%, and the agreement quotient (kappa) was 0.976. The detection limits of the real-time PCR assays for M. bovis and M. tuberculosis genomic DNA were 10 fg and 0.1 pg per PCR reaction, respectively. Consequently, this multiplex real-time PCR assay is a useful diagnotic tool for the identification of MTC and differentiation of M. bovis and M. tuberculosis, as well as the epidemiologic surveillance of animals slaughtered in abattoir.

Selection of Low Toxic Pesticides and Residual Toxicity to Cotesia glomerata (배추나비고치벌 (Cotesia glomerata)에 대한 저독성 약제 및 잔류독성)

  • Choi, Byeong-Ryeol;Lee, Si-Woo;Park, Hyung-Man
    • Korean journal of applied entomology
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    • v.46 no.2
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    • pp.251-259
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    • 2007
  • For the development of integrated pest management system by harmonizing biological and chemical control, some experiments wee carried out to select low toxic pesticides against natural enemies. and their residual toxicity were evaluated. Leaf dipping method, body dipping method, and diet treatment method were set up for the toxicity evaluation against Cotesia glomerata adults. We had tested 46 different pesticides (31 insecticides, 11 fungicides, 4 herbicides) at recommending concentration commonly used to control diamond back moth, disease and up-land weeds in chinese cabbage field. Twenty three insecticides, eleven fungicides, and four herbicides were shown to be low toxic to C. glomerata adults in the treatment of body dipping. After insecticide spraying at recommending dose on the chinese cabbage, we examined residual effect of insecticides by introducing natural enemies on different days. Safety interval for the introduction of C. glomerata adults was established according to the residual toxicity of pesticides. Safe insecticides for the introduction of C. glomerata adults at one day after treatment (DAT) were thiacloprid, acephate, chlorfenapyr, clothianidin and at 3 DAT were imidacloprid, deltamethrin, thiamethoxam, dimethylvinphos, emamectin benzoate.

Heavy Metal Contents and Antioxidant Activity and Cytotoxic Effect of Red Sea Bream (Pagrus major): Comparative Studies in Domestic and Imported Red Sea Bream (Pagrus major) (국내산 및 수입산 참돔의 중금속 함량 및 항산화 활성과 세포독성 효과 비교)

  • Hwang, Seong Yeon;Bae, Jin Han;Lim, Sun-Young
    • Journal of Life Science
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    • v.25 no.4
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    • pp.450-455
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    • 2015
  • This study compared the heavy metal contents and the effects of extracts from domestic and imported red sea bream on the antioxidant activity and cytotoxicity of human cancer cell lines. The antioxidant activity was measured using the fluorescently sensitive dye, 2’-7’ dichlorofluorescein-diacetate (DCFH-DA), and antiproliferative activity against AGS human gastric adenocarcinoma and HT-29 human colon cancer cell lines, which was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Domestic red sea bream had a higher mercury content when compared to imported red sea bream, but there was no significant difference in the lead content. Treatments with acetone/methylene chloride (A+M) and methanol (MeOH) extracts from domestic and imported red sea bream dose-dependently decreased the H2O2 induced ROS production, compared to the control. The cell viability showed that treatments with the A+M and MeOH extracts had cytotoxicity in the growth of AGS and HT-29 cancer cells. In the case of AGS, the extracts from the domestic red sea bream were higher in inhibiting cancer cell growth, compared to imported red sea bream. Our results demonstrate that the heavy metal contents of domestic and imported red sea bream were below the limit of the Food Code of Korea. The results of the biological activities indicate that the antioxidant activity of extracts from imported red sea bream was more effective, while the extracts from the domestic red sea bream were stronger in cytotoxic activity.

Formation of Biogenic Amines by Lactobacillus plantarum Isolated from Makgeolli (막걸리에서 분리한 Lactobacillus plantarum의 biogenic amine 생성능)

  • Kwak, Hee Jung;Kim, Jae Young;Lee, Hyun Sook;Kim, Soon Mi
    • Korean Journal of Food Science and Technology
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    • v.46 no.4
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    • pp.438-445
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    • 2014
  • We examined biogenic amine (BA) production as well as the diversity of bacterial flora in 11 types of commercial makgeolli stored at 4 and $20^{\circ}C$. Moreover, we studied the BA-producing activity of three L. plantarum strains isolated from makgeolli. At $20^{\circ}C$, the BA content was highly increased and the denatured DNA bands were more variable in non-sterilized makgeolli compared to sterilized makgeolli. The major BAs produced in commercial makgeolli were histamine and putrescine. Histamine, tyramine, putrescine, and cadaverine were produced in excess by inoculation of the three L. plantarum isolates to makgeolli stored at $20^{\circ}C$ for 21 days. These results suggest that some L. plantarum strains in makgeolli can produce different types of BAs, depending on the extent of degradation of makgeolli.

Effects of Concrete Materials for the Stream Restoration on Bombina orientalis Embryos (하천복원용 콘크리트 소재가 무당개구리 (Bombina orientalis) 배아에 미치는 영향)

  • Park, Chan Jin;Ahn, Hong Kyu;Gye, Myung Chan;Lee, Tae Hyeong
    • Ecology and Resilient Infrastructure
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    • v.2 no.2
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    • pp.147-153
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    • 2015
  • Various adverse effects can occur due to direct exposure from toxic substances when toxic materials are used to restore river ecosystems. Thus, this study performed analysis on the development of toxicity in terms of survival and abnormality rates using embryos of Bombina orientalis living in Korea to analyze the toxicity of materials used in the river projects. The results showed that the toxicity in cement (C group) was the strongest whereas the toxicity in plant-based polyurethane (P1 group) was the weakest. Survival rates of B. orientalis embryos were 100%, 94 - 95%, 66 - 89% and 0% in control, P1, polyurethane (P2) and C groups, respectively. Abnormalities of embryos were 10.5%, 5.3 - 10.5%, 26.3 - 27.8% and 35.7% in control, P1, P2 and C groups, respectively. Furthermore, we verified that having a sufficient curing time reduced toxic substances that were extracted. The above result suggest that cement and polyurethane hamper the early development of amphibians. In conclusion, it is highly important to review biological safety with respect to the selection of materials used to restore rivers. This study shows the importance of the selection of eco-friendly materials and processes.

Development of a Prototype Patient Monitoring System with Module-Based Bedside Units and Central Stations: Overall Architecture and Specifications (모듈형 환자감시기와 중앙 환자감시기로 구성되는 환자감시시스템 시제품의 개발: 전체구조 및 사양)

  • Woo, E.J.;Park, S.H.;Jun, B.M.;Moon, C.W.;Lee, H.C.;Kim, S.T.;Kim, H.J.;Seo, J.J.;Chae, K.M.;Park, J.C.;Choi, K.H.;Lee, W.J.;Kim, K.S.
    • Proceedings of the KOSOMBE Conference
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    • v.1996 no.05
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    • pp.315-319
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    • 1996
  • We have developed a prototype patient monitoring system including module-based bedside units, interbed network, and central stations. A bedside unit consists of a color monitor and a main CPU unit with peripherals including a module controller. It can also include up to 3 module cases and 21 different modules. In addition to the 3-channel recorder module, six different physiological parameters of ECG, respiration, invasive blood pressure, noninvasive blood pressure, body temperature, and arterial pulse oximetry with plethysmogaph are provided as parameter modules. Modules and a module controller communicate with up to 1Mbps data rate through an intrabed network based on RS-485 and HDLC protocol. Bedside units can display up to 12 channels of waveforms with any related numeric informations simultaneously. At the same time, it communicates with other bedside units and central stations through interbed network based on 10Mbps Ethernet and TCP/IP protocol. Software far bedside units and central stations fully utilizes gaphical user interface techniques and all functions are controlled by a rotate/push button on bedside unit and a mouse on central station. The entire system satisfies the requirements of AAMI and ANSI standards in terms of electrical safety and performances. In order to accommodate more advanced data management capabilities such as 24-hour full disclosure, we are developing a relational database server dedicated to the patient monitoring system. We are also developing a clinical workstation with which physicians can review and examine the data from patients through various kinds of computer networks far diagnosis and report generation. Portable bedside units with LCD display and wired or wireless data communication capability will be developed in the near future. New parameter modules including cardiac output, capnograph, and other gas analysis functions will be added.

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