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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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Effect of Verapamil on Cellular Uptake of Tc-99m MIBI and Tetrofosmin on Several Cancer Cells (수종의 암세포에서 Verapamil이 Tc-99m MIBI와 Tetrofosmin의 섭취에 미치는 영향)

  • Kim, Dae-Hyun;Yoo, Jung-Ah;Suh, Myung-Rang;Bae, Jin-Ho;Jeong, Shin-Young;Ahn, Byeong-Cheol;Lee, Kyu-Bo;Lee, Jae-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.1
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    • pp.85-98
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    • 2004
  • Purpose: Cellular uptake of $^{99}mTc$-sestamibi (MIBI) and $^{99}mTc$-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. Materials and Methods: Celluar uptakes of Tc-99m MIBI and TF were measured in erythroleukermia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto $200{\mu}M\;at\;1{\times}10^6\;cells/ml\;at\;37^{\circ}C$. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. Results: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr) cell at a concentration of $100{\mu}M$ and the maximal increase at $50{\mu}M$ was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over $1{\mu}M$. With a concentration of $200{\mu}M$ verapamil, MIBI and TF uptakes un K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with $10{\mu}M$, but were also decreased with verapamil higher than $10{\mu}M$, resulting 40% and 5% of baseline at $50{\mu}M$. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at $200{\mu}M$. Conclusion: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.

The Location of Medical Facilities and Its Inhabitants' Efficient Utilization in Kwangju City (광주시(光州市) 의료시설(醫療施設)의 입지(立地)와 주민(住民)의 효율적(效率的) 이용(利用))

  • Jeon, Kyung-Sook
    • Journal of the Korean association of regional geographers
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    • v.3 no.2
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    • pp.163-193
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    • 1997
  • Medical services are a fundamental and essential service in all urban areas. The location and accessibility of medical service facilities and institutions are critical to the diagnosis, control and prevention of illness and disease. The purpose of this paper is to present the results of a study on the location of medical facilities in Kwangju and the utilization of these facilities by the inhabitants. The following information is a summary of the findings: (1) Korea, like many countries, is now witnessing an increase in the age of its population as a result of higher living standards and better medical services. Korea is also experiencing a rapid increase in health care costs. To ensure easy access to medical consultation, diagnosis and treatment by individuals, the hierarchical efficient location of medical facilities, low medical costs, equalized medical services, preventive medical care is important. (2) In Korea, the quality of medical services has improved significantly as evident by the increased number of medical facilities and medical personnel. However, there is still a need for not only quantitative improvements but also for a more equitable distribution of and location of medical services. (3) There are 503 medical facilities in Kwangju each with a need to service 2,556 people. This is below the national average of 1,498 inhabitants per facility. The higher locational quotient and satisfactory population per medical facility showed at the civic center. On the other hand, problem regions such as the traditional residential area in Buk-Gu, Moo-deung mountain area and the outer areas of west Kwangju still maintain rural characteristics. (4) In the study area there are 86 general medicine clinics which provide basic medical services. i. e. one clinic per every 14,949 residents. As a basic service, its higher locational quotient showed in the residential area. The lower population concentration per clinic was found in the civic center and in the former town center, Songjeong-dong. In recently build residential areas and in the civic center, the lack of general medicine clinics is not a serious medical services issue because of the surplus of medical specialists in Korea. People are inclined to seek a consultation with a specialist in specific fields rather than consult a general practitioner. As a result of this phenomenon, there are 81 internal medicine facilities. Of these, 32.1% provide services to people who are not referred by a primary care physician but who self-diagnose then choose a medical facility specializing in what they believe to be their health problem. Areas in the city, called dongs, without any internal facilities make up 50% of the total 101 dongs. (5) There are 78 surgical facilities within the area, and there is little difference at the locational appearance from internal medicine facilities. There are also 71 pediatric health clinics for people under 15 years of age in this area, represents one clinic per 5,063 people. On the quantitative aspect, this is a positive situation. Accessibility is the most important facility choice factor, so it should be evenly located in proportion to demander distribution. However, 61% of 102 dongs have no pediatric clinics because of the uneven location. (6) There are 43 obstetrical and gynecological clinics in Kwangju, and the number of residents being served per clinic is 15,063. These services need to be given regularly so it should increase the numbers. There are 37 ENT clinics in the study area with the lower concentration in Dong-gu (32.4%) making no locational differences by dong. There are 23 dermatology clinics with the largest concentration in Dong-Gu. There are 17 ophthalmic clinics concentrated in the residential area because of the primary function of this type of specialization. (7) The use of general medicine clinics, internal medicine clinics, pediatric clinics, ENT clinics by the inhabitants indicate a trend toward primary or routine medical services. Obstetrics and gynecology clinics are used on a regular basis. In choosing a general medicine clinic, internal medicine clinic, pediatric clinic, and a ENT clinic, accessibility is the key factor while choice of a general hospital, surgery clinic, or an obstetrics and gynecology clinic, thes faith and trust in the medical practitioner is the priority consideration. (8) I considered the efficient use of medical facilities in the aspect of locational and management and suggest the following: First, primary care facilities should be evenly distributed in every area. In Kwangju, the number of medical facilities is the lowest among the six largest cities in Korea. Moreover, they are concentrated in Dong-gu and in newly developed areas. The desired number of medical facilities should be within 30 minutes of each person's home. For regional development there is a need to develop a plan to balance, for example, taxes and funds supporting personnel, equipment and facilities. Secondly, medical services should be co-ordinated to ensure consistent, appropriate, quality services. Primary medical facilities should take charge of out-patient activities, and every effort should be made to standardize and equalize equipment and facility resources and to ensure ongoing development and training in the primary services field. A few specialty medical facilities and general hospitals should establish a priority service for incurable and terminally ill patients. (9) The management scheme for the inhabitants' efficient use of medical service is as follows: The first task is to efficiently manage medical facilities and related services. Higher quality of medical services can be accomplished within the rapidly changing medical environment. A network of social, administrative and medical organizations within an area should be established to promote information gathering and sharing strategies to better assist the community. Statistics and trends on the rate or occurrence of diseases, births, deaths, medical and environment conditions of the poor or estranged people should be maintained and monitored. The second task is to increase resources in the area of disease prevention and health promotion. Currently the focus is on the treatment and care of individuals with illness or disease. A strong emphasis should also be placed on promoting prevention of illness and injury within the community through not only public health offices but also via medical service facilities. Home medical care should be established and medical testing centers should be located as an ordinary service level. Also, reduced medical costs for the physically handicapped, cardiac patients, and mentally ill or handicapped patients should be considered.

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