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Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study

  • Peter, Aniekan Imo;Naidu, Edwin CS;Akang, Edidiong;Ogedengbe, Oluwatosin O;Offor, Ugochukwu;Rambharose, Sanjeev;Kalhapure, Rahul;Chuturgoon, Anil;Govender, Thirumala;Azu, Onyemaechi O
    • Toxicological Research
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    • v.34 no.3
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    • pp.221-229
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    • 2018
  • Tenofovir nanoparticles are novel therapeutic intervention in human immunodeficiency virus (HIV) infection reaching the virus in their sanctuary sites. However, there has been no systemic toxicity testing of this formulation despite global concerns on the safety of nano drugs. Therefore, this study was designed to investigate the toxicity of Tenofovir nanoparticle (NTDF) on the liver and kidney using an animal model. Fifteen adult male Sprague-Dawley (SD) rats maintained at the animal house of the biomedical resources unit of the University of KwaZulu-Natal were weighed and divided into three groups. Control animals (A) were administered with normal saline (NS). The therapeutic doses of Tenofovir (TDF) and nanoparticles of Tenofovir (NTDF) were administered to group B and C and observed for signs of stress for four weeks after which animals were weighed and sacrificed. Liver and kidney were removed and fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT) and liver function test (LFT). Cellular measurements and capturing were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, p values < 0.05 were significant. We observed no signs of behavioural toxicity and no mortality during this study, however, in the kidneys, we reported mild morphological perturbations widening of Bowman's space, and vacuolations in glomerulus and tubules of TDF and NTDF animals. Also, there was a significant elevation of glycogen deposition in NTDF and TDF animals when compared with control. In the liver, there were mild histological changes with widening of sinusoidal spaces, vacuolations in hepatocytes and elevation of glycogen deposition in TDF and NTDF administered animals. In addition to this, there were no significant differences in stereological measurements and cell count, LFT, RFT, weight changes and organo-somatic index between treatment groups and control. In conclusion, NTDF and TDF in therapeutic doses can lead to mild hepatic and renal histological damage. Further studies are needed to understand the precise genetic mechanism.

Transgenic Plants with Enhanced Tolerance to Environmental Stress by Metabolic Engineering of Antioxidative Mechanism in Chloroplasts (엽록체 항산화기구 대사조절에 의한 환경스트레스 내성 식물)

  • Kwon Suk-Yoon;Lee Young-Pyo;Lim Soon;Lee Haeng-Soon;Kwak Sang-Soo
    • Journal of Plant Biotechnology
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    • v.32 no.3
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    • pp.151-159
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    • 2005
  • Injury caused by reactive oxygen species (ROS), known as oxidative stress, is one of the major damaging factors in plants exposed to environmental stress. Chloroplasts are specially sensitive to damage by ROS because electrons that escape from the photosynthetic electron transfer system are able to react with relatively high concentration of $O_2$ in chloroplasts. To cope with oxidative stress, plants have evolved an efficient ROS-scavenging enzymes such as superoxide dismutase (SOD) and ascorbate peroxidase (APX), and low molecular weight antioxidants including ascorbate, glutathione and phenolic compounds. To maintain the productivity of plants under the stress condition, it is possible to fortify the antioxidative mechanisms in the chloroplasts by manipulating the antioxidation genes. A powerful gene expression system with an appropriate promoter is key requisite for excellent stress-tolerant plants. We developed a strong oxidative stress-inducible peroxidase (SWPA2) promoter from cultured cells of sweetpotato (Ipomoea batatas) as an industrial platform technology to develop transgenic plants with enhanced tolerance to environmental stress. Recently, in order to develop transgenic sweetpotato (tv. Yulmi) and potato (Solanum tuberosum L. cv. Atlantic and Superior) plants with enhanced tolerance to multiple stress, the genes of both CuZnSOD and APX were expressed in chloroplasts under the control of an SWPA2 promoter (referred to SSA plants). As expected, SSA sweetpotato and potato plants showed enhanced tolerance to methyl viologen-mediated oxidative stress. In addition, SSA plants showed enhanced tolerance to multiple stresses such as temperature stress, drought and sulphur dioxide. Our results strongly suggested that the rational manipulation of antioxidative mechanism in chloroplasts will be applicable to the development of all plant species with enhanced tolerance to multiple environmental stresses to contribute in solving the global food and environmental problems in the 21st century.

Differences in Dietary Life and Health related Factors According to Obesity in Poor Urban Peruvian Adolescents (페루 도시 빈민지역 청소년의 비만에 따른 식생활 및 건강요인의 차이)

  • Chung, Hye-Kyung;Lee, Hae-Young;Kim, Jin Ri;Nam, Eun Woo
    • Korean Journal of Community Nutrition
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    • v.23 no.4
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    • pp.302-318
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    • 2018
  • Objectives: This study examined the differences in dietary life and health related factors, such as drinking behavior, exercise and leisure activities, mental health, and subjective perception for oneself according to obesity in poor urban Peruvian adolescents. Methods: A total of 1,532 Peruvian adolescents were selected from six schools in poor regions using stratified random sampling. The subjects were classified into two groups based on their BMI: 'normal weight group (NW group=980)' or 'overweight and obese group (OWOB group=293)'. The differences in the general characteristics, dietary life, drinking behavior, physical activity and leisure, mental health and subjective perception of oneself in the two groups were compared. ${\chi}^2$ analysis and independent sample t-test were performed using the SPSS program ver. 24. Results: For the total and male students, the frequency of breakfast and dinner were significantly lower in the OWOB group than in the NW group (all p<0.001). For total and female students, the percentage of subjects who received nutrition education was significantly higher in the OWOB group than in the NW group (all p<0.05). For total students, the percentage of subject who exercised more than five days/week was lower in the OWOB group than in the NW group (p<0.05). For the total and female students, the subjective health status was worse in the OWOB group than in the NW group (all p<0.05). The subjective body image was significantly different between the OWOB group and NW group in the total, male and female subjects (all p<0.001). Conclusions: The frequency of meals and exercise, and the subjective perceptions of the health status and body image differed according to obesity in poor urban Peruvian adolescents. Therefore, a school-based intervention program focused on regular meal and exercise, and adequate subjective perceptions for health status and body image need to be developed to prevent adolescent obesity.

Evaluation on the Mechanical Performance of Concrete Using Entanglement Polyamide Fiber (다발형 폴리아미드섬유 보강 콘크리트의 역학적 성능평가)

  • Jeon, Joong Kyu;Kim, Gyu Yong;Jeon, Chan Ki;Lee, Soo Choul
    • Journal of the Society of Disaster Information
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    • v.8 no.3
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    • pp.223-233
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    • 2012
  • Steel fiber is high stiffness and large weight. So, Pumping hose to rupture of the safety management is difficult. Steel fiber caused by corrosion of the deterioration of durability and high-rebound losses are needed for the improvements. Thus, the revised regulations in 2009 by a steel fiber to reinforce other materials is possible. Variety of fiber reinforcement material for concrete review of applicability is needed. Steel fiber strength than the other fibers is large and by the geometry of the fibers are attached to improve performance. However, compared to steel fiber organic fibers and low modulus of elasticity and tensile strength of fiber and agglomeration occurs in the concrete to be used as reinforcement material is difficult. In this regard, the present study as a single object in the micro-fiber bouquet sharp entanglement through make muck attach surface area, distributed fibers from surfactant of the surface enhanced polyamide fibers, steel fiber and PP fiber reinforced concrete by comparing the scene to provide a basis for the use.

Suicide Related Indicators and Trends in Korea in 2018 (2018년 자살 관련 지표들과 추이)

  • Lee, Doo Woong;Kwon, Junhyun;Yang, Jieun;Ju, Yeong Jun;Park, Eun-Cheol;Jang, Sung-In
    • Health Policy and Management
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    • v.30 no.1
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    • pp.112-119
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    • 2020
  • Suicide has been a long-standing problem for global public health, along with almost 800,000 deaths from suicide worldwide in 2016, accounting for 1.4% of all deaths. South Korea was ranked first in suicide mortality in 2018 among countries in the Organization for Economic Cooperation and Development. This study aimed to suggest up-to-date information about suicide-related indicators such as the rate of suicidal ideation, suicide attempt, and suicide death, and its trends by applying sampling weight to make it nationally representative. In this study, we used the data sources: Korea National Health and Nutrition Examination (KNHANES, '07-13, '15-18), Korean Community Health Survey (KCHS, '08-09, '13, '17), Korean Wealth Panel Study (KOWEPS, '12-18), Korea Health Panel Survey (KHP, '10-13), and Statistics Korea (1983-2017). The rate of suicidal ideation as recent year was 4.73% (KNHANES, '17), 6.96% (KCHS, '17), 2.29% (KOWEPS, '18), and 5.39% (KHP, '13). That of suicide attempt as recent year was 0.51% (KNHANES, '18), 0.32% (KCHS, '17), and 0.15% (KOWEPS, '18). Annual percentage change (APC) of suicidal ideation was -15.4% (KNHANES, '07-13, '15, '17), -2.5% (KCHS, '08-09, '13, '17), -10.8% (KOWEPS, '12-18), and -10.9% (KHP, '10-13). APC of suicide attempt was -4.4% (KNHANES, '07-13, '15-18), -4.4% (KCHS, '08-09, '13, '17), and -13.6% (KOWEPS, '12-18). APC of death by intentional self-harm was -1.25% (Statistics Korea, '07-18). All suicide-related indicators were found to be decreasing in the overall from 2009. Individuals with lower income level were more likely to experience suicidal ideation and suicide attempts. Even though suicide rate had been continuously decreasing from its highest point in 2011 (suicide rate: 31.7 per 100,000 population) to 2017 (suicide rate: 24.3 per 100,000 population), it increased again in 2018 (suicide rate: 26.6 per 100,000 population). This information would be grounded on policy implementation for suicide prevention, thus continuous data observation is necessary.

The Physiological Responses of Spotted Seahorse Hippocampus kuda to Low-pH Water (사육수의 pH변화가 복해마(Hippocampus kuda)에 미치는 생리적 영향)

  • Park, Cheonman;Kim, Ki-hyuk;Moon, Hye-Na;Yeo, In-Kyu
    • Journal of Life Science
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    • v.27 no.7
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    • pp.826-833
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    • 2017
  • The rising concentration of atmospheric carbon dioxide is causing ocean acidification and global warming. The seahorse is an important species in marine ecosystems and fishery markets, however, their populations have recently decreased due to ocean acidification. As a result, we examined changes in the physiological responses of the spotted seahorse Hippocampus kuda when it was exposed to acidic sea water (pH 6.0, 6.5, and 7.0) and normal seawater (pH 8.0 as the control) over a period of 15 days. As the pH decreased, the seahorses' body weight and length also decreased. Components in body of ash, the crude lipids and crude proteins also differed significantly with changes in pH, due to stress caused by the seahorses' exposure to the acidic water conditions. The superoxide dismutase levels were significantly lower in the pH 6.0 and 6.5 groups than they were in the pH 7.0 and pH 8.0 groups. However, the catalase and glutathione levels were significantly higher in the acidic sea water groups. We suggest that decreasing the pH level of rearing water induces a stress response in H. kuda, damaging their ability to maintain their homeostasis and energy metabolism. Antioxidant enzymes are generally sensitive to acidic stress; in this study, the antioxidant activity was significantly affected by the pH level of the rearing water. These results indicate that physiological stress, induced by exposure to acidification, induces an antioxidant reaction, which can reduce general components in the body and the growth of H. kuda.

An ESDA Tool for Time-series Spatial Association (지역분석을 위한 시계열 공간연관성 탐색도구)

  • Ahn Jae-Seong;Park Key-Ho;Lee Yang-Won
    • Spatial Information Research
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    • v.14 no.1 s.36
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    • pp.163-176
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    • 2006
  • The concept of 'spatial association' explains spatial distribution pattern of geographical phenomenon based on similarity with neighborhoods, as in the Tobler's Law of Geography: 'Everything is related to everything else, but near things are more related than distant things.' In this study, we develop a time-series exploratory analysis tool for discovering temporal patterns of spatial association by combining spatial statistics and geo-visualization, and thus present a possibility to support spatial decision-making process. As for the spatial proximity weight matrix indispensable to measuring global and local spatial association, we employ a variety of flexible weighting schemes using geometric characteristics of areal unit. In addition, we renovate the existing visualization methods for more effective understanding of the procedures and results of time-series analysis on spatial association: for instance, temporal parallel coordinate plot with box plot, animated map for spatial association, and 3D Moran scatterplot. The feasibility of our system is verified by time-series analysis experiments on the spatial association of land price fluctuation rate for all administrative units in Korea, $1995{\sim}2004$.

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The Efficacy and Safety of Moclobemide Twice Daily : An Open Trial in Patients with Major Depressive Disorder (1회 2회 분복 투여하는 Moclobemide의 효과와 안전성 : 주요우울장애 환자에서 개방 시험)

  • Yoon, Jin-Sang;Lee, Hyung-Young;Kook, Seung-Hee;Choi, Young
    • Korean Journal of Biological Psychiatry
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    • v.3 no.1
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    • pp.102-108
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    • 1996
  • This was an open trial to evaluate the efficacy and safety of moclobemide twice daily for treatment of Korean patients with major depressive disorder(DSM-III-R). The duration of the trial was 6 weeks with the initial dose of moclobemide being fixed lor the first two weeks at 300mg/day(150mg twice daily, each token after morning and evening meals). Thereafter, when necessary, the dose was allowed to increase to 600mg/day or decrease to 150mg/day according to the seventy of the depression and/or the tolerability of the drug. Hypnotics and/or sedatives from a benzodiazepine group could be concomitantly administered at usual dosage. Patients were assessed at baseline and at days 14, 28 and 42. Efficacy was primarily judged on the Hamilton Rating Scale for Depression(HAM-D) and Beck Depression Inventory(BDI). Patients had to score at least 17 respectively an both scales to enter the trial. Secondary efficacy parameters included Clinical Global Impression(CGI) for severity of illness and improvement. Safety and tolerability were judged on reported adverse events, vital signs and laboratory parameters. In addition, there was a series of questions and assessments for the psychiatrists and patients to complete at the end of the trial Twenty nine patients completing trial were included in the analysis of efficacy : of thirty one patients participating in the safety and tolerability analysis, those who withdraw voluntarily without particular reasons or violated the treatment schedule were not included. The efficacies as determined by HAM-D, BDI or CGI were found to be significant compared to baseline. The number of responders defined as patients with a total score of 10 or less or with a total score of 50% or less of the baseline score on HAM-D and BDI were 17(59%) and 18(62%) respectively. Regarding safety and tolerability, nine patients(29%) reported mild adverse events probably related to moclobemide : of these one patient dropped out because of poor tolerability : however, there were no appreciable changes in blood pressure, pulse rate, body weight or laboratory parameters for all patients over the trial period. Furthermore, the physicians' and patients' opinions at final evaluation showed that moclabemide has a good antidepressant effect as well as a favorable tolerability. In conclusion, a twice-daily dosage schedule with maclobemide is recommendable for the treatment of Korean patients with major depressive disorder since its efficacy and safety were demonstrated in this study.

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An Analysis on the North-Africa Entry Strategies of Korea Logistics Companies (조선산업의 글로벌 경쟁력 강화를 위한 한중 선박금융제도의 비교연구)

  • Choi, Chang-Yeoul;Ham, Hyung-Bum
    • International Commerce and Information Review
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    • v.14 no.4
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    • pp.317-337
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    • 2012
  • This study has investigated shipping finance systems in Korea and China, and extracted negative factors based on it to propose a way to develop the shipping financial system in Korea for shipbuilding industry and marine transportation. From after the global financial crisis in 2008 to right before the Lehman Brothers Holdings bankruptcy, shipping finance has been dominated by the major industrialized countries in Europe. However, the weight point is moving to the countries in Asia region such as Korea, Japan, and China based on relatively strong banking system and low interests rate. This study focused on the alternatives the current situation that the starter of shipping finance among three countries in Northeast Asia, South Korea is facing China's challenges. In the paper, shipping finance in Korea presented its defectives such as the limits of ship financing, lack of professional workforces, ever-present foreign exchange risks, and lack of understandings of the parties. As the countermeasures of them, it proposed establishing professional institute for ship financing, training professionals in financial industry, raising foreign credentials of won, and continuing associations between the parties. Even though we are the first Asian country introduced ship funds, the ship funds growth in China shall be under our eyes while we keep systemic networks between shipping, ship building, and ship financing.

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The Structural Equivalence and Role Equivalence of Container Ports in Asia-Europe Container Shipping Networks (아시아-유럽 컨테이너 해운 네트워크 구성 항만의 구조적 등위성과 역할 등위성)

  • Lee, Sang-Yoon
    • Journal of Korea Port Economic Association
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    • v.32 no.2
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    • pp.105-122
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    • 2016
  • Numerous studies have evaluated the status of seaports. However, the majority of the research has approached this topic from the view-point of port capabilities, including locational advantage, infrastructure, productivity, and competitiveness. The position and/or role of a port can be understood more precisely and comprehensively by considering the interconnectivity among ports making up enormous global transportation networks. The main objective of this study is to compare the status of 82 container ports on the trunk shipping routes between Asia and Europe by applying the concepts of structural equivalence and role equivalence proposed by the social network analysis method. Network similarities and differences among competing ports in the regions are assessed by analysing their structural equivalence. Furthermore, the hierarchical structures of the ports located on the trunks between Asia and Northwest Europe and between Asia and the Mediterranean are constructed by evaluating their role equivalence. The results of this empirical research shows that Singapore and Rotterdam possess the most significant positions on the ocean corridors between Asia and Northwest Europe. Singapore also holds a leading position on the Asia-Mediterranean shipping route. Lastly, no ports located in the Middle East or Mediterranean regions have an equivalent weight to those of Rotterdam, Hamburg, Antwerp on the Asia-Northwest Europe route.