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The Ability of Anti-tumor Necrosis Factor Alpha(TNF-${\alpha}$) Antibodies Produced in Sheep Colostrums

  • Yun, Sung-Seob
    • 한국유가공학회:학술대회논문집
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    • 2007.09a
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    • pp.49-58
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    • 2007
  • Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.

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Effects of climate change on biodiversity and measures for them (생물다양성에 대한 기후변화의 영향과 그 대책)

  • An, Ji Hong;Lim, Chi Hong;Jung, Song Hie;Kim, A Reum;Lee, Chang Seok
    • Journal of Wetlands Research
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    • v.18 no.4
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    • pp.474-480
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    • 2016
  • In this study, formation background of biodiversity and its changes in the process of geologic history, and effects of climate change on biodiversity and human were discussed and the alternatives to reduce the effects of climate change were suggested. Biodiversity is 'the variety of life' and refers collectively to variation at all levels of biological organization. That is, biodiversity encompasses the genes, species and ecosystems and their interactions. It provides the basis for ecosystems and the services on which all people fundamentally depend. Nevertheless, today, biodiversity is increasingly threatened, usually as the result of human activity. Diverse organisms on earth, which are estimated as 10 to 30 million species, are the result of adaptation and evolution to various environments through long history of four billion years since the birth of life. Countlessly many organisms composing biodiversity have specific characteristics, respectively and are interrelated with each other through diverse relationship. Environment of the earth, on which we live, has also created for long years through extensive relationship and interaction of those organisms. We mankind also live through interrelationship with the other organisms as an organism. The man cannot lives without the other organisms around him. Even though so, human beings accelerate mean extinction rate about 1,000 times compared with that of the past for recent several years. We have to conserve biodiversity for plentiful life of our future generation and are responsible for sustainable use of biodiversity. Korea has achieved faster economic growth than any other countries in the world. On the other hand, Korea had hold originally rich biodiversity as it is not only a peninsula country stretched lengthily from north to south but also three sides are surrounded by sea. But they disappeared increasingly in the process of fast economic growth. Korean people have created specific Korean culture by coexistence with nature through a long history of agriculture, forestry, and fishery. But in recent years, the relationship between Korean and nature became far in the processes of introduction of western culture and development of science and technology and specific natural feature born from harmonious combination between nature and culture disappears more and more. Population of Korea is expected to be reduced as contrasted with world population growing continuously. At this time, we need to restore biodiversity damaged in the processes of rapid population growth and economic development in concert with recovery of natural ecosystem due to population decrease. There were grand extinction events of five times since the birth of life on the earth. Modern extinction is very rapid and human activity is major causal factor. In these respects, it is distinguished from the past one. Climate change is real. Biodiversity is very vulnerable to climate change. If organisms did not find a survival method such as 'adaptation through evolution', 'movement to the other place where they can exist', and so on in the changed environment, they would extinct. In this respect, if climate change is continued, biodiversity should be damaged greatly. Furthermore, climate change would also influence on human life and socio-economic environment through change of biodiversity. Therefore, we need to grasp the effects that climate change influences on biodiversity more actively and further to prepare the alternatives to reduce the damage. Change of phenology, change of distribution range including vegetation shift, disharmony of interaction among organisms, reduction of reproduction and growth rates due to odd food chain, degradation of coral reef, and so on are emerged as the effects of climate change on biodiversity. Expansion of infectious disease, reduction of food production, change of cultivation range of crops, change of fishing ground and time, and so on appear as the effects on human. To solve climate change problem, first of all, we need to mitigate climate change by reducing discharge of warming gases. But even though we now stop discharge of warming gases, climate change is expected to be continued for the time being. In this respect, preparing adaptive strategy of climate change can be more realistic. Continuous monitoring to observe the effects of climate change on biodiversity and establishment of monitoring system have to be preceded over all others. Insurance of diverse ecological spaces where biodiversity can establish, assisted migration, and establishment of horizontal network from south to north and vertical one from lowland to upland ecological networks could be recommended as the alternatives to aid adaptation of biodiversity to the changing climate.