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Post HCV Infection Due to MX Gene Stimulation Produced Post Treatment with Imported and Locally Produced Egyptian Biosimilar IFN

  • Mohamed, Shereen H;Mahmoud, Nora F;Mohamed, Aly F;Kotb, Nahla S
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5635-5641
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    • 2015
  • Background: Cirrhosis is regarded as a possible end stage of many liver diseases, including viral infection. It occurs when healthy liver tissue becomes damaged and is replaced by scar tissue and finally may lead to hepatocellular carcinoma. Interferons (IFNs)are two general categories, type I and II. Type I includes one beta interferon and over 20 different alpha interferons. Alpha interferons are very similar in how they work, interacting with other proteins on cells like receptors. The main objective of this study was to compare Mx gene productivity post different cell line treatment with imported and Egyptian biosimilar locally produced IFNs, as well as the efficacy of those tested IFNs. Also, an assessment was made of sensitivity of different cell lines as alternatives to that recommended for evaluation of antiviral activity. Materials and Methods: Different cell lines (Vero, MDBK and Wish) were employed to evaluate cytotoxicity using the MTT assay. Antiviral activity was evaluated compared with standard IFN against VSV, Indiana strain -156, on tested rh-IFNs (imported; innovated and Egyptian biosimilar locally produced IFNs) in the pre-treated cell lines previously mentioned. The virus was propagated in the Wish cell line as recommended. Finally we estimated up-regulation of the Mx gene as a biomarker. Results: Data recorded revealed that test IFNs were safe in test cell lines. Viability was around 100%. Locally tested interferon did not realize the international potency limits, while the imported one was accepted compared with the standard IFN. These results were the same either using infectivity titer reduction assay or crystal violet staining of residual non- infected cells. Mx protein production was cell type related and confirmed by the detected Mx gene expressed in imported and locally produced IFN pre-treated cell lines. The expression of the gene was arranged in the order of Vero> wish > MDBK for the imported IFN, while for the Egyptian biosimillar locally produced one it was MDBK> Vero> wish. With regard to the antiviral activity there was a significant difference of imported IFN potency compared with the locally produced IFN (P<0.05), the IFN potential (antiviral activity) was not cell line related and showed non-significant difference for each separate product. Conclusions: Vero cells can be used as an alternative cell line for evaluation of IFN potency in case of unavailable USP recommended cell lines. Alternative potency evaluation assay could be used and proved significant difference in IFN potency in case of local and imported agents. Evaluation of antiviral activity could be used in parallel to viral infectivity reduction assay for better accuracy. Mx gene can be used as a marker for IFN potential.

Contamination of Chinese Cabbage Soil with Plasmodiophora brassicae (배추 산지 토양의 뿌리혹병균 오염)

  • Soh, Jae-Woo;Han, Kyung-Sook;Lee, Seong-Chan;Lee, Jung-Sup
    • Research in Plant Disease
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    • v.19 no.3
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    • pp.201-207
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    • 2013
  • This research was performed to establish basic technology for Chinese cabbage clubroot chemical control by investigating the soil contamination of Plasmodiophora brassicae in major producing regions of fall Chinese cabbage. PCR primers were developed to detect P. brassicae, a causal agent of Chinese cabbage club-root that generally occurs in Cruciferae family. A primer set, PbbtgF761 and PbbtgR961, specifically amplified a 245 bp fragment from P. brassicae only. At places well known for fall Chinese cabbage, 10 out of 33 in Haenam-gun, 5 out of 13 in Yeongam-gun and Yeonggwang-gun, 1 out of 6 in Gochang-gun, 2 out of 12 in Hongseong-gun, and 5 out of 17 in Dangjin-si resulted positive for P. brassicae contamination. The results show that the soil contamination rate of P. brassicae was 30.3% in Haenam-gun, 38.5% in Yeongam-gun and Yeonggwang-gun, 16.7% in Gochang-gun, 16.7% in Hongseong-gun, and 29.4% in Dangjin-si. The six places where Chinese cabbage clubroot was visible by naked eye were 100% confirmed by the PCR test of the P. brassicae contaminated soil. Thus, simple PCR test may be utilized as an index to decide on chemical control of P. brassicae.

Bioequivalence of Two Nilvadipine Tablet (닐바디핀 정제에 대한 생물학적 동등성 평가)

  • 김종국;이사원;최한곤;고종호;이미경;김인숙
    • Biomolecules & Therapeutics
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    • v.6 no.3
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    • pp.289-295
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    • 1998
  • The bioequivalence of two nilvadipine products was evaluated in 16 normal male volunteers (age 22-32 yr, body weight 57-80 kg) following sidle oral dose. Test product was Overca $l_{R}$ tablet (Choong-Wae Pharm. Corp., Korea) and reference product was Nivadi $l_{R}$ tablet (Hyundai Pharm. Corp., Korea). Both products contain 4 mg of nilvadipine. One tablet of the test or the reference product was administered to the volunteers, respectively, by randomized two period cross-over study (2$\times$2 Latin square method). The determination of nilvadipine was accomplished using a validated capillary column GC with electron-capture detection. As a result of the assay validation, the quantiflcation of nilvadipine in human plasma by this technique was possible down to 0.5 ng/ml using 1 ml of plasma. Absolute overall recovery from five replicate analyses of nilvadipine-spiked sample were 88.4$\pm$ 10.24% (mean$\pm$ 5.D.) for human plasma of 10 ng/ml. The coefficients of variation (C.V.) were less than 20% and the actual concentration of nilvadipine measured by GC ranged from 80 to 99% in all plasma. Average drug concentrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products (p>0.05); the area under the curve from time zero to 8 hr (AUCo-$_{8 hr}$) (22.8$\pm$5.90 vs 22.2$\pm$6.10 ng . hr/ml), maximum plasma concentration ( $C_{max}$) (10.0$\pm$2.85 vs 9.3$\pm$3.28 ng/ml) and time to reach maximum plasma concentration ( $T_{max}$) (1.2$\pm$0.31 vs 1.3 $\pm$0.47 hr). The differences of mean AU $Co_{8hr}$ $C_{max}$, and $T_{max}$ between the two products (2.25, 7.65, and 10.30%, respectively) were less than 20%. The power (1-$\beta$) and treaeent difference (7) for AU $Co_{8hr}$, and $C_{max}$ were more than 0.8 and less than 0.2, respectively. Although the power for Tmax was under 0.8, Tm\ulcorner of the two products was not significantly different from each other (p>0. 05). These results suggest that the bioavailability of Overeat tablet is not significantly different from that of Nivadil tablet. Therefore, two products are bioequivalent based on the current results.sults.lts.lts.lts.

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Bioequivalence of Lovaload Tablet to Mevacor Tablet (Lovastatin 20 mg) (메바코 정 (로바스타틴 20 mg)에 대한 로바로드 정의 생물학적 동등성)

  • Song, Woo-Heon;Kim, Jung-Min;Cho, Seong-Wan;Kim, Jae-Hyun;Lim, Jong-Lae;Shin, Hee-Jong;Choi, Young-Wook
    • Journal of Pharmaceutical Investigation
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    • v.28 no.4
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    • pp.283-288
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    • 1998
  • Lovastatin, one of the potent cholesterol-lowering agents, is an inactive lactone prodrug which is metabolized to its active open acid, lovastatin acid (LVA). Bioequivalence study of two lovastatin preparations, the test drug ($Mevacor^{\circledR}$: Chungwae Pharmaceutical Co., Ltd.) and the reference drug ($Lovaload^{\circledR}$: Chong Kun Dang Pharmaceutical Co., Ltd.), was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Fourteen healthy male volunteers, $23.9{\pm}3.9$ years old and $67.6{\pm}8.0$ kg of body weight in average, were divided randomly into two groups and administered the drug orally at the dose of 160 mg as lovastatin in a $2{\times}2$ crossover study. Plasma concentrations of lovastatin acid were analysed by HPLC method for 12 hr after administration. The extent of bioavailability was obtained from the plasma concentration-time profiles of total lovastatin acid after alkaline hydrolysis of the plasma samples. By alkaline hydrolysis, trace amounts of unmetabolized lovastatin were converted to lovastatin acid. The $AUC_{0-12hr}$ was calculated by the linear trapezoidal rule method. The $C_{max}$ and $T_{max}$ were compiled directly from the plasma drug concentration-time data. Student's t-test indicated no significant differences between the formulations in these parameters. Analysis of variance (ANOVA) revealed that there were no differences in AUC, $C_{max}$, and $T_{max}$ between the formulations. The apparent differences between the formulations were far less than 20% (e.g., 7.07, 5.77 and 1.18% for AUC, $C_{max}$, and $T_{max}$, respectively). Minimum detectable differences(%) between the formulations at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 17.2, 15.1, and 15.9% for AUC, Cmax, and Tmax, respectively). The 90% confidence intervals for these parameters were also within ${\pm}20%$ (e.g.. $-5.20{\sim}19.3$, $-5.00{\sim}16.5$, and $-10.2{\sim}12.5%$ for AUC, $C_{max}$, and $T_{max}$, respectively). These results satisfied the bioequivalence criteria of KFDA guidelines, indicating that the two formulations of lovastatin were bioequivalent.

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Characterization of Bacteriocin, lacticin YH-10, Produced by Lactococcus lactis subsp. lactis YH-10 Isolated from Kimchi (김치유산균인 Lactococcus lactis subsp. lactis YH-10가 생산하는 박테리오신의 특성)

  • Park, Eun-Min;Kim, Young-Hwa;Park, So-Jin;Kim, Yun-Im;Ha, Yu-Mi;Kim, Sung-Koo
    • Journal of Life Science
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    • v.14 no.4
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    • pp.683-688
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    • 2004
  • A bacteriocin-producing lactic acid bacteria was isolated from Kimchi on MRS selective media with the use of Lactobacillus delbrueckii subsp. delbrueckii as an indicator strain. The strain YH-10 was identified as Lactococcus lactis subsp. lactis through the API test. The crude bacteriocin (freeze-dried 50% ammonium sulfate precipitate of culture supernatant) produced by the strain was named as lacticin YH-10. Lacticin YH-10 showed the growth inhibitory activity against Gram positive pathogenic bacteria and other lactic acid bacteria. The bacteriocin was inactivated by proteases such as protamex and aroase AP-10 and partially inactivated by amylase, proteinase K, trypsin, and papain. The lacticin YH-10 remained its activity with the treatment of heat at 10$0^{\circ}C$ for 60 min or the changes of pH 2 to 11. However, the activity was lost at high pH combined with the exposure to 10$0^{\circ}C$. The bacteriocin production of the strain was started in the exponential phase and stopped in the stationary phase. The approximate molecular mass of the bacteriocin produced by the strain was approximate 14 kDa in the analysis on SDS-PAGE.

A STUDY OF WORKING EFFICIENCY AND FILE DEFORMATION OF GT ROTARY FILE IN CURVED CANALS (GT rotary file을 이용한 만곡 근관형성시 작업 효율 및 file 변형 발생에 관한 연구)

  • 신주희;백승호;배광식;임성삼;윤수한;김병현
    • Restorative Dentistry and Endodontics
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    • v.26 no.5
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    • pp.418-435
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    • 2001
  • Root canal preparation process is of utmost importance in successful treatment of root canal. Also, one of the most important purpose of the root canal preparation is to enlarge the root canal three dimensionally without changing the curvature of the root canal However as the curvature of the root canal increases, there are many difficulties involved in formation of optimum root canal. Therefore in order to solve the above mentioned problems, new developments in methods of root canal preparation and equipments for such purposes were made. Recently, vigorous studies about newly introduced engine-driven nickel-ti-tanium rotary file are conducted. As shown in research results to dates, it is well established that the use of nickel-titanium file is better suited for curved root canal than stainless steel file in maintaining the curvature or root canal and reducing the deformation of root canal. However it is also acknowledged that there are a few discrepancies in research results according to protocol, due to failure to remove variables in experiments. In addition, although it is recommended by the manufacturer that the GT rotary file should maintain a low rotational speed of 150~350rpm and 'light pressure' as light as not to break the lead of a pencil, academic studies about the vertical force which is not yet standardized are not sufficiently explored. Therefore, this research devised and utilized a special research equipment to standardize the appropriate range of vertical force for GT rotary file through experiments by breaking of the lead of a pencil as expressed by the manufacturer and to accurately measure factors involved through repeating and recreating the environment of root canal preparation. Forming nine experimental groups by varying the vertical forces (150g. 220g, 300g) and rpm (150rpm, 250rpm, 350rpm), the effects of changing vertical forces and rpm on working efficiency were measured in terms of time expended in root canal preparation by crown-down method using a transparent resin block with 35 degree curvature and GT rotary file (z-test). The following research using this special research equipment that involved nine experimental groups and varying the vertical force for root canal preparation from 300g which is within the normal vertical force range to 700g and 1000g which fall outside the normal rpm range. The results were as follows : 1. Analysis of the experiment results revealed that the time spent in root canal preparation decreased as the vertical forces and rpm increased (p<0.05). Also, the effects of rpm were greater than those of the vertical forces within the normal vertical force range ($\beta$-weight test). 2. Observation of the deformation of GT rotary file revealed that deformation increases in a direct correlation with the vertical force increase and in a reverse correlation with the rpm decrease. In the case of the vertical forces close to the normal range, the probability of GT rotary file deformation were quite different depending on the rpm changes. In the case of greater vertical forces, the occurrences of deformation of the file were more frequent regardless of the rpm changes. 3. Deformation and breakage of file were also commonly observed in the expended time measurement experiments and GT rotary file deformation experiments in which low speed rpm (150rpm) was used and at the curved portion of the resin block.

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Analysis on the Microbial Community Structure of Red Granule in the Anaerobic Ammonium Oxidation Reactor (혐기성 암모늄 산화 반응기 내 붉은색 입상슬러지의 미생물 군집구조 분석)

  • Bae, Hyo-Kwan;Park, Kyung-Soon;Chung, Yun-Chul;Jung, Jin-Young
    • Journal of Korean Society of Environmental Engineers
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    • v.28 no.10
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    • pp.1055-1064
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    • 2006
  • Extremely slow growing anammox(anaerobic ammonium oxidation) bacteria were cultivated using a combination of UASB(Upflow Anaerobic Sludge Blanket) reactor seeded with anaerobic granular sludge and carbon-fiber cultivating reactor. After 180 days of continuous cultivation, average nitrogen removal rate showed 0.54 kg $N/m^3-day$ when 0.6 kg $N/m^3-day$ of nitrogen loading was applied. The black granule was changed to brown and red granule as continuous operation, and the red granule was highly dependant on the high anammox activity. Microbial community structure of red granule in the UASB reactor was analyzed by molecular methods such as gene cloning, phylogenetic tree analysis, and FISH(Fluorescence In Situ Hybridization) method. As a result of gene cloning and phylogenetic tree analysis, 5 kinds of phylum were found to be Planctomycetes, Proteobacteria, Acidobacteria, Chlorobi and Chloroflexi. 13 clones were matched to anammox bacteria among 51 clones in the red anammox granule. In-silico test which used cloning information and FISH probe of the AMX368 was conducted to detect the presence of anammox bacteria in the red anammox granule. As a result of in-silico test only one clone was exactly matched to AMX368 but 11 clones was mutated one base among 18 bases representing all 12 clones are anammox bacteria. A filamentous Chloroflexi might be related to the granulation of anammox bacteria. As a result of FISH analysis, anammox bacteria was abundant in the red anammox granule.

Damage Study on the Mechanical Fastening in Laminated Composites (복합적층판(復合積層板)의 기계적(機械的) 체결부(締結部)에 관한 파손연구(破損硏究))

  • Kwan-Hyung,Song
    • Bulletin of the Society of Naval Architects of Korea
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    • v.27 no.4
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    • pp.58-66
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    • 1990
  • A series of test was performed measuring the failure strength and failure mode of Gr/Pi, $[0^{\circ}/45^{\circ}/90^{\circ}/-45^{\circ}]_s$ laminate containing a single pin loaded hole. The finite element method is applied to calculate the stress distribution in the laminates, then the failure load and the failure mode were predicted by means of the characteristic length. 12 different geometric variations were developed to analyze the effects of the ratio of specimen width to hole diameter (W/d) and ratio of edge distance to hole diameter (L/d). X-Ray of NDE methods were utilized in finding out the initial defects, damage and the fracture mechanism, and SEM(Scanning Electron Microscopes) was used the evaluation of the fracture mechanism and crack propagation around hole under tension pin loading. $[0^{\circ}/45^{\circ}/90^{\circ}/-45^{\circ}]_s$ laminate are found to be most sensitive to W/d but not so influenced by L/d. The failure mode and tensile strength predicted by the model show agreement with experiment data for pin loading bolted jointed test except range of $L/d{\leqq}3$.

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Changes in surface roughness of bracket and wire after experimental sliding - preliminary study using an atomic force microscopy (브라켓과 탄선 간의 마찰 전후 표면 변화 분석 - 원자현미경을 이용한 예비연구)

  • Lee, Tae-Hee;Park, Ki-Ho;Jeon, Ji-Yun;Kim, Su-Jung;Park, Hun-Kuk;Park, Young-Guk
    • The korean journal of orthodontics
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    • v.40 no.3
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    • pp.156-166
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    • 2010
  • Objective: The surface roughness of orthodontic materials is an essential factor that determines the coefficient of friction and the effectiveness of tooth movement. The aim of this study is to evaluate the surface roughness change of the brackets and wires after experimental sliding quantitatively. Methods: Before and after experimental sliding tests, the surface roughness of stainless steel brackets, ceramic brackets, stainless steel wires, and beta-titanium (TMA) wires were investigated and compared using atomic force microscopy (AFM). Results: After sliding tests, changes in the surface of the wire were greater than changes in the bracket slot surface. The surface roughness of the stainless steel bracket was not significantly increased after sliding test, whereas the roughness of ceramic brackets was decreased. Both the surface roughness of stainless steel and TMA wires were increased after sliding test. More changes were observed on the ceramic bracket than the stainless steel bracket. Conclusions: AFM is a valuable research tool when analyzing the surface roughness of the brackets and wires quantitatively.

Median Control Chart for Nonnormally Distributed Processes (비정규분포공정에서 메디안특수관리도 통용모형설정에 관한 실증적 연구(요약))

  • 신용백
    • Journal of Korean Society of Industrial and Systems Engineering
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    • v.10 no.16
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    • pp.101-106
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    • 1987
  • Statistical control charts are useful tools to monitor and control the manufacturing processes and are widely used in most Korean industries. Many Korean companies, however, do not always obtain desired results from the traditional control charts by Shewhart such as the $\bar{X}$-chart, $\bar{X}$-chart, $\bar{X}$-chart, etc. This is partly because the quality charterstics of the process are not distributed normally but are skewed due to the intermittent production, small lot size, etc. In Shewhart $\bar{X}$-chart. which is the most widely used one in Kora, such skewed distributions make the plots to be inclined below or above the central line or outside the control limits although no assignable causes can be found. To overcome such shortcomings in nonnormally distributed processes, a distribution-free type of confidence interval can be used, which should be based on order statistics. This thesis is concerned with the design of control chart based on a sample median which is easy to use in practical situation and therefore properties for nonnormal distributions may be easily analyzed. Control limits and central lines are given for the more famous nonnormal distributions, such as Gamma, Beta, Lognormal, Weibull, Pareto, Truncated-normal distributions. Robustness of the proposed median control chart is compared with that of the $\bar{X}$-chart; the former tends to be superior to the latter as the probability distribution of the process becomes more skewed. The average run length to detect the assignable cause is also compared when the process has a Normal or a Gamma distribution for which the properties of X are easy to verify, the proposed chart is slightly worse than the $\bar{X}$-chart for the normally distributed product but much better for Gamma-distributed products. Average Run Lengths of the other distributions are also computed. To use the proposed control chart, the probability distribution of the process should be known or estimated. If it is not possible, the results of comparison of the robustness force us to use the proposed median control chart based oh a normal distribution. To estimate the distribution of the process, Sturge's formula is used to graph the histogram and the method of probability plotting, $\chi$$^2$-goodness of fit test and Kolmogorov-Smirnov test, are discussed with real case examples. A comparison of the proposed median chart and the $\bar{X}$ chart was also performed with these examples and the median chart turned out to be superior to the $\bar{X}$-chart.

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