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Effects of Bacillus Calmette-Guerin (BCG) on the DNA Synthesis of Mouse Duodenal Mucosal Epithelial Cells Inoculated with Ehrlich Carcinoma Cells (Bacillus Calmette-Guerin (BCG) 투여가 Ehrlich 종양세포를 이식한 생쥐 샘창자 상피세포의 DNA합성에 미치는 영향)

  • Ko, Jeong-Sik;Kim, Heung-No;Park, Kyung-Ho;Park, Dae-Kyoon;Kim, Duk-Soo
    • Applied Microscopy
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    • v.40 no.4
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    • pp.193-200
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    • 2010
  • This experiment was performed to evaluate the morphological responses of the duodenal epithelial cells of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of Bacillus Calmette-Guerin (BCG). In the experimental groups, each mouse was inoculated with $1{\times}10^7$ Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day after inoculations, 0.2 mL of saline or BCG (0.5 mL/25 g B.W.: $0.03{\times}10^8\sim0.32{\times}10^8$ CFU) were injected subcutaneously to the animals every other day, respectively. The day following the 7th injection of saline or BCG, each mouse was injected with a single dose of $0.7{\mu}Ci$/g of methyl-$^3H$-thymidine (25 Ci/mmol, Amersham Lab, England) through tail vein. Seventy minutes after the thymidine injection, animals were sacrificed, and duodenal tissues were taken and fixed in 10% neutral formalin. Deparaffinized sections were coated with autoradiographic emulsion EM-1 (Amersham Lab, England) in a dark room and dried and were placed in a light-tight box. The number of labeled epithelial cells in the duodenal mucosae (mean number of labeled epithelial cells per 3.5 mm length of mucosa) were observed and calculated. On the light microscopic study, duodenal mucosae had no severe morphological changes following the injection of BCG. In the tumor control and BCG treated groups, a number of small lymphocytes and eosinophile leucocytes are slightly increased as compared with those of the normal control ones. On the autoradiographic study, number of the labeled cells of normal control, tumor control and BCG-treated mice were 632.3 (${\pm}14.47$), 761.7 (${\pm}27.65$) and 505.0 (${\pm}17.09$) respectively. From the above results, BCG may suppress the DNA synthesis of the duodenal epithelial cells, but does not results severe structural defect on the duodenal mucosae. And it is suggested that BCG may greatly improve the anticancer therapy on certain kind of cancer.

Effects of BCG on the DNA Synthesis and Ultrastructure of Mouse Gastric Mucosal Epithelial Cells Inoculated with Ehrlich Carcinoma Cells (BCG가 Ehrlich 암세포를 이식한 생쥐의 위점막 상피세포의 DNA합성 및 미세구조에 미치는 영향)

  • Ko, Jeong-Sik;Ryoo, In-Sang;Park, Kyung-Ho;Park, Dae-Kyoon
    • Applied Microscopy
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    • v.39 no.3
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    • pp.205-218
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    • 2009
  • This experiment was performed to evaluate the morphological responses of the gastric epithelial cells of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of BCG. Healthy adult ICR mice weighing 25 gm each were divided into normal and experimental groups (tumor control group and BCG-treated group). In the experimental groups, each mouse was inoculated with $1{\times}10^7$ Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day after inoculations, 0.2 mL of saline or BCG (0.5 mL/25 g B.W.: $0.03{\times}10^8{\sim}0.32{\times}10^8$ CFU) were injected subcutaneously to the animals every other day, respectively. The day following the 7th injection of saline or BCG, each mouse was injected with a single dose of 0.7 ${\mu}Ci/g$ of methyl-$^3H$-thymidine (25 Ci/mmol, Amersham Lab., England) through tail vein. Seventy minutes after the thymidine injection, animals were sacrificed, and gastric tissues were taken and fixed in 10% neutral formalin. Deparaffinized sections were coated with autoradiographic emulsion EM-1 (Amersham Lab., England) in a dark room. The number of labeled epithelial cells in the gastric mucosae (mean number of labeled epithelial cells per 3.5 mm length of mucosa) were observed and calculated. And for electron microscopic observation, gastric tissues were prefixed with 2.5% glutaraldehyde-1.5% paraformaldehyde solution, followed by post-fixation with 1% osmium tetroxide solution. On the light microscopic study, gastric mucosae had no morphological changes following the injection of BCG. On the electron microscopic study, in the BCG-treated mice, myelin figures and multivesicular bodies within the gastric epithelial cells were observed more frequently than in those of the normal control ones. On the autoradiographic study, number of the labeled cells of normal control, tumor control and BCG-treated mice were 380.2 (${\pm}31.35$), 426.1 (${\pm}28.43$) and 301.8 (${\pm}34.63$), respectively. In the BCG-treated mice, poorly-labeled cells containing only a few silver grains of 3H-thymidine were observed more frequently as compared in those of the normal control and tumor control ones. From the above results, BCG may suppress the DNA synthesis of the gastric epithelial cells, but does not results severe fine structural defect on the gastric epithelial cells. These results suggest that BCG is expected as one of the effective supplemental anticancer drugs.

Herbicidal Phytotoxicity under Adverse Environments and Countermeasures (불량환경하(不良環境下)에서의 제초제(除草劑) 약해(藥害)와 경감기술(輕減技術))

  • Kwon, Y.W.;Hwang, H.S.;Kang, B.H.
    • Korean Journal of Weed Science
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    • v.13 no.4
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    • pp.210-233
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    • 1993
  • The herbicide has become indispensable as much as nitrogen fertilizer in Korean agriculture from 1970 onwards. It is estimated that in 1991 more than 40 herbicides were registered for rice crop and treated to an area 1.41 times the rice acreage ; more than 30 herbicides were registered for field crops and treated to 89% of the crop area ; the treatment acreage of 3 non-selective foliar-applied herbicides reached 2,555 thousand hectares. During the last 25 years herbicides have benefited the Korean farmers substantially in labor, cost and time of farming. Any herbicide which causes crop injury in ordinary uses is not allowed to register in most country. Herbicides, however, can cause crop injury more or less when they are misused, abused or used under adverse environments. The herbicide use more than 100% of crop acreage means an increased probability of which herbicides are used wrong or under adverse situation. This is true as evidenced by that about 25% of farmers have experienced the herbicide caused crop injury more than once during last 10 years on authors' nationwide surveys in 1992 and 1993 ; one-half of the injury incidences were with crop yield loss greater than 10%. Crop injury caused by herbicide had not occurred to a serious extent in the 1960s when the herbicides fewer than 5 were used by farmers to the field less than 12% of total acreage. Farmers ascribed about 53% of the herbicidal injury incidences at their fields to their misuses such as overdose, careless or improper application, off-time application or wrong choice of the herbicide, etc. While 47% of the incidences were mainly due to adverse natural conditions. Such misuses can be reduced to a minimum through enhanced education/extension services for right uses and, although undesirable, increased farmers' experiences of phytotoxicity. The most difficult primary problem arises from lack of countermeasures for farmers to cope with various adverse environmental conditions. At present almost all the herbicides have"Do not use!" instructions on label to avoid crop injury under adverse environments. These "Do not use!" situations Include sandy, highly percolating, or infertile soils, cool water gushing paddy, poorly draining paddy, terraced paddy, too wet or dry soils, days of abnormally cool or high air temperature, etc. Meanwhile, the cultivated lands are under poor conditions : the average organic matter content ranges 2.5 to 2.8% in paddy soil and 2.0 to 2.6% in upland soil ; the canon exchange capacity ranges 8 to 12 m.e. ; approximately 43% of paddy and 56% of upland are of sandy to sandy gravel soil ; only 42% of paddy and 16% of upland fields are on flat land. The present situation would mean that about 40 to 50% of soil applied herbicides are used on the field where the label instructs "Do not use!". Yet no positive effort has been made for 25 years long by government or companies to develop countermeasures. It is a really sophisticated social problem. In the 1960s and 1970s a subside program to incoporate hillside red clayish soil into sandy paddy as well as campaign for increased application of compost to the field had been operating. Yet majority of the sandy soils remains sandy and the program and campaign had been stopped. With regard to this sandy soil problem the authors have developed a method of "split application of a herbicide onto sandy soil field". A model case study has been carried out with success and is introduced with key procedure in this paper. Climate is variable in its nature. Among the climatic components sudden fall or rise in temperature is hardly avoidable for a crop plant. Our spring air temperature fluctuates so much ; for example, the daily mean air temperature of Inchon city varied from 6.31 to $16.81^{\circ}C$ on April 20, early seeding time of crops, within${\times}$2Sd range of 30 year records. Seeding early in season means an increased liability to phytotoxicity, and this will be more evident in direct water-seeding of rice. About 20% of farmers depend on the cold underground-water pumped for rice irrigation. If the well is deep over 70m, the fresh water may be about $10^{\circ}C$ cold. The water should be warmed to about $20^{\circ}C$ before irrigation. This is not so practiced well by farmers. In addition to the forementioned adverse conditions there exist many other aspects to be amended. Among them the worst for liquid spray type herbicides is almost total lacking in proper knowledge of nozzle types and concern with even spray by the administrative, rural extension officers, company and farmers. Even not available in the market are the nozzles and sprayers appropriate for herbicides spray. Most people perceive all the pesticide sprayers same and concern much with the speed and easiness of spray, not with correct spray. There exist many points to be improved to minimize herbicidal phytotoxicity in Korea and many ways to achieve the goal. First of all it is suggested that 1) the present evaluation of a new herbicide at standard and double doses in registration trials is to be an evaluation for standard, double and triple doses to exploit the response slope in making decision for approval and recommendation of different dose for different situation on label, 2) the government is to recognize the facts and nature of the present problem to correct the present misperceptions and to develop an appropriate national program for improvement of soil conditions, spray equipment, extention manpower and services, 3) the researchers are to enhance researches on the countermeasures and 4) the herbicide makers/dealers are to correct their misperceptions and policy for sales, to develop database on the detailed use conditions of consumer one by one and to serve the consumers with direct counsel based on the database.

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Studies on the red-yellow soil in Honam rolling area - Improvement of soil fertility - (호남야산(湖南野山)에 분포(分布)하고 있는 적황색(赤黃色)에 관(關)한 연구(硏究) - 토양비옥도(土壤肥沃度) 증진(增進)에 관(關)하여 -)

  • Chae, Sang Suk;Chang, Young Sun;Lee, Hwa Soo;Hong, Chong Woon
    • Korean Journal of Soil Science and Fertilizer
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    • v.7 no.1
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    • pp.29-34
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    • 1974
  • On a newly reclamed acidic Song-jong soil (soil of a member of fine loamy, mesic family of Hapludults) an experiment was carried out to find out the proper measure of the improvement of soil fertility with soybean as test crop. Results are summarized as follow: 1. Application of compost (1 ton/10a), lime (lime requirement)and fused phosphate (equivalent to 5% of the phosphate fixation coefficient)resulted in the increase of soybean yield by 93.3% over the check plot (N: 6kg/10a, $P_2O_5$: 9kg/10a, $K_2O$: 6kg/10a). The application of fused phosphate at the level of 5% of phosphate fixation coefficient N (6kg/10a) and K(6kg/10a) brought the yield increase by 62.7% over the check plot. However, although the pH of the soil was adjusted to 7.0 by liming, the application of lime with moderate dose of phosphate ($P_2O_5$: 9kg/10a) did not increase the yield of soybean significantly. And the application of fused phosphate at the level of 5% of phosphate fixation coefficient increased the available soil P from 14 ppm to around 100 ppm as tested after harvest. 2. Application of compost (1 ton/10a) increased the organic matter content of soil by 0.8% when tested after harvest. While, the application of rice straw (0.5 ton/10a) did not alter the soil organic matter content. The CEC of the soil tested after havest found incereased significantly by the addition of lime and compost. 3. Plant analysis revealed that the $K_2O/Ca+Mg$ is better correlated with the yield than the absolute concentration of $K_2O$ in plant tissue. Between the concentration of $P_2O_5$ in plant tissue and the yield of soybean, a typical C-curve relationship was observed, indicating that in this particular soil, phosphate was the primary growth liming factor.

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Optimization of Tube Voltage according to Patient's Body Type during Limb examination in Digital X-ray Equipment (디지털 엑스선 장비의 사지 검사 시 환자 체형에 따른 관전압 최적화)

  • Kim, Sang-Hyun
    • Journal of the Korean Society of Radiology
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    • v.11 no.5
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    • pp.379-385
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    • 2017
  • This study identifies the optimal tube voltages depending on the changes in the patient's body type for limb tests using a digital radiography (DR) system. For the upper-limp test, the dose area product (DAP) was fixed at $5.06dGy{\ast} cm^2$, and for the lower-limb test, the DAP was fixed at $5.04dGy{\ast} cm^2$. Afterwards, the tube voltage was changed to four different stages and the images were taken three times at each stage. The thickness of the limbs was increased by 10 mm to 30 mm to change in the patient's body type. For a quantitative evaluation, Image J was used to calculate the contrast to noise ratio (CNR) and signal to noise ratio (SNR) among the four groups, according to the tube voltage. For statistical testing, the statistically significant differences were analyzed through the Kruskal-Wallis test at a 95% confidence level. For the qualitative analysis of the images, the pre-determined items were evaluated based on a 5-point Likert scale. In both upper-limb and lower-limb tests, the more the tube voltage increased, the more the CNR and SNR of the images decreased. The test on the changes depending on the patient's body shape showed that the more the thickness increased, the more the CNR and SNR decreased. In the qualitative evaluation on the upper limbs, the more the tube voltage increased, the more score increased to 4.6 at the maximum of 55kV and 3.6 at 40kV, respectively. The mean score for the lower limbs was 4.4, regardless of the tube voltage. The more either the upper or lower limbs got thicker, the more the score generally decreased. The score of the upper limps sharply dropped at 40kV, whereas that of the lower limps sharply dropped at 50kV. For patients with a standard thickness, the optimized images can be obtained when taken at 45kV for the upper limbs, and at 50kV for the lower limbs. However, when the thickness of the patient's limbs increases, it is best to set the tube voltage at 50 kV for the upper limbs and at 55 kV for the lower limbs.

Variability in Drug Interaction According to Genetic Polymorphisms in Drug Metabolizing Enzymes

  • Jang, In-Jin;Yu, Kyung-Sang;Cho, Joo-Youn;Chung, Jae-Yong;Kim, Jung-Ryul;Lim, Hyeong-Seok;Shin, Sang-Goo
    • Environmental Mutagens and Carcinogens
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    • v.24 no.1
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    • pp.15-18
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    • 2004
  • There are significant differences in the extent of drug interactions between subjects. The influence of the genetic make up of drug metabolizing enzyme activities (CYP3A5, CYP2C19 and UDP-glucuronosyl transferase) on the pharmacokinetic drug interaction potential were studied in vivo. Nineteen healthy volunteers were grouped with regard to the $CYP3A5^{*}3$ allele, into homozygous wild-type (CYP3A5^{*}1/1^{*}1$, n=6), heterozygous $(CYP3A5^{*}1/^{*}3$, n=6), and homozygous variant-type $(CYP3A5^{*}3/^{*}3$, n=7) subject groups. The pharmacokinetic profile of intravenous midazolam was characterized before and after itraconazole administration (200 mg once daily for 4 days), and also following rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. For omeprazole and moclobemide pharmacokinetic interaction study 16 healthy volunteers were recruited. The volunteer group comprised 8 extensive metabolizers and 8 poor metabolizers of CYP2C19, which was confirmed by genotyping. Subjects were randomly allocated into two sequence groups, and a single-blind, placebo-controlled, two-period crossover study was performed. In study I, a placebo was orally administered for 7 days. On the eighth morning, 300 mg of moclobemide and 40 mg of placebo were coadministered with 200 mL of water, and a pharmacokinetic study was performed. During study n, 40 mg of omeprazole was given each morning instead of placebo, and pharmacokinetic studies were performed on the first and eighth day with 300 mg of moclobemide coadministration. In the UGT study pharmacokinetics and dynamics of 2 mg intravenous lorazepam were evaluated before and after rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. The subjective and objective pharmacodynamic tests were done before and 1, 2, 4, 6, 8, and 12 hrs after lorazepam administration. The pharmacokinetic profiles of midazolam and of its hydroxy metabolites did not show differences between the genotype groups under basal and induced metabolic conditions. However, during the inhibited metabolic state, the $CYP3A5^{*}3/^{*}3$ group showed a greater decrease in systemic clearance than the $CYP3A5^{*}1/^{*}1$ group $(8.5\pm3.8$ L/h/70 kg vs. $13.5\pm2.7$ L/h/70 kg, P=0.027). The 1'-hydroxymidazolam to midazolam AUC ratio was also significantly lower in the $CYP3A5^{*}3/^{*}3$,/TEX> group $(0.58\pm0.35,$ vs. $1.09\pm0.37$ for the homozygous wild-type group, P=0.026). The inhibition of moclo-bemide metabolism was significant in extensive metabolizers even after a single dose of omeprazole. After daily administration of omeprazole for 1 week, the pharmacokinetic parameters of moclobemide and its metabolites in extensive metabolizers changed to values similar to those in poor metabolizers. In poor meta-bolizers, no remarkable changes in the pharmacokinetic parameters were observed. The area under the time-effect curves of visual analog scale(VAS), choice reaction time, and continuous line tracking test results of lorazepam was reduced by 20%, 7%, 23% respectively in induced state, and in spite of large interindividual variablity, significant statistical difference was shown in VAS(repeated measures ANOVA, p=0.0027).

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Glass Dissolution Rates From MCC-1 and Flow-Through Tests

  • Jeong, Seung-Young
    • Proceedings of the Korean Radioactive Waste Society Conference
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    • 2004.06a
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    • pp.257-258
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    • 2004
  • The dose from radionuclides released from high-level radioactive waste (HLW) glasses as they corrode must be taken into account when assessing the performance of a disposal system. In the performance assessment (PA) calculations conducted for the proposed Yucca Mountain, Nevada, disposal system, the release of radionuclides is conservatively assumed to occur at the same rate the glass matrix dissolves. A simple model was developed to calculate the glass dissolution rate of HLW glasses in these PA calculations [1]. For the PA calculations that were conducted for Site Recommendation, it was necessary to identify ranges of parameter values that bounded the dissolution rates of the wide range of HLW glass compositions that will be disposed. The values and ranges of the model parameters for the pH and temperature dependencies were extracted from the results of SPFT, static leach tests, and Soxhlet tests available in the literature. Static leach tests were conducted with a range of glass compositions to measure values for the glass composition parameter. The glass dissolution rate depends on temperature, pH, and the compositions of the glass and solution, The dissolution rate is calculated using Eq. 1: $rate{\;}={\;}k_{o}10^{(ph){\eta})}{\cdot}e^{(-Ea/RT)}{\cdot}(1-Q/K){\;}+{\;}k_{long}$ where $k_{0},\;{\eta}$ and Eaare the parameters for glass composition, pH, $\eta$ and temperature dependence, respectively, and R is the gas constant. The term (1-Q/K) is the affinity term, where Q is the ion activity product of the solution and K is the pseudo-equilibrium constant for the glass. Values of the parameters $k_{0},\;{\eta}\;and\;E_{a}$ are the parameters for glass composition, pH, and temperature dependence, respectively, and R is the gas constant. The term (1-Q/C) is the affinity term, where Q is the ion activity product of the solution and K is the pseudo-equilibrium constant for the glass. Values of the parameters $k_0$, and Ea are determined under test conditions where the value of Q is maintained near zero, so that the value of the affinity term remains near 1. The dissolution rate under conditions in which the value of the affinity term is near 1 is referred to as the forward rate. This is the highest dissolution rate that can occur at a particular pH and temperature. The value of the parameter K is determined from experiments in which the value of the ion activity product approaches the value of K. This results in a decrease in the value of the affinity term and the dissolution rate. The highly dilute solutions required to measure the forward rate and extract values for $k_0$, $\eta$, and Ea can be maintained by conducting dynamic tests in which the test solution is removed from the reaction cell and replaced with fresh solution. In the single-pass flow-through (PFT) test method, this is done by continuously pumping the test solution through the reaction cell. Alternatively, static tests can be conducted with sufficient solution volume that the solution concentrations of dissolved glass components do not increase significantly during the test. Both the SPFT and static tests can ve conducted for a wide range of pH values and temperatures. Both static and SPFt tests have short-comings. the SPFT test requires analysis of several solutions (typically 6-10) at each of several flow rates to determine the glass dissolution rate at each pH and temperature. As will be shown, the rate measured in an SPFt test depends on the solution flow rate. The solutions in static tests will eventually become concentrated enough to affect the dissolution rate. In both the SPFt and static test methods. a compromise is required between the need to minimize the effects of dissolved components on the dissolution rate and the need to attain solution concentrations that are high enough to analyze. In the paper, we compare the results of static leach tests and SPFT tests conducted with simple 5-component glass to confirm the equivalence of SPFT tests and static tests conducted with pH buffer solutions. Tests were conducted over the range pH values that are most relevant for waste glass disssolution in a disposal system. The glass and temperature used in the tests were selected to allow direct comparison with SPFT tests conducted previously. The ability to measure parameter values with more than one test method and an understanding of how the rate measured in each test is affected by various test parameters provides added confidence to the measured values. The dissolution rate of a simple 5-component glass was measured at pH values of 6.2, 8.3, and 9.6 and $70^{\circ}C$ using static tests and single-pass flow-through (SPFT) tests. Similar rates were measured with the two methods. However, the measured rates are about 10X higher than the rates measured previously for a glass having the same composition using an SPFT test method. Differences are attributed to effects of the solution flow rate on the glass dissolution reate and how the specific surface area of crushed glass is estimated. This comparison indicates the need to standardize the SPFT test procedure.

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Hepatic Parenchrmal Changes After Percutaneous Injection of Holmium-166 in Rabbit (가토 간내에 Holmium-166 주입 후의 간 실질 변화)

  • 최병인;김명진;박영년;김주희;최병욱
    • Investigative Magnetic Resonance Imaging
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    • v.5 no.1
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    • pp.43-48
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    • 2001
  • Purpose : To evaluate changes in rabbit liver parenchyma on MR images following percutaneous Holmium-166 injection, and to correlate those changes with histologic findings. Materials and methods. Holmium-166 (10-25 mCi) was percutaneously injected into the liver of rabbit (n=12) under sonographic guidance. MR images were obtained between one to two weeks (acute phasea) after the injection in four rabbits, and between two to four weeks (subacute phase) after the injection in four rabbits. Tissue specimens of these eight rabbits were obtained immediately after MR imaging. Tissue specimens were obtained without MR imaging in four rabbits (between one to two weeks in one rabbit and between three to four weeks in three rabbits). Results : Tissue specimens showed central liquefactive necrosis and peripheral coagulative necrosis containing deposition of small particles and hemorrhage. The peripheral margin of the lesions showed formation of the granulation tissue with fibrosis, which tended to be more prominent in subacute phase. The area of the necrosis tended to correlate with the dose of the radioactive Holmium-166. On MR images, the central portion of the necrosis showed hyperintensity on 72-weighted image, hypointensity on the precontrast T1-weighted images, and no enhancement on the dynamic MR images. The peripheral portion of the necrosis showed hypointensity on T2-weighted images, iso or mild hypointensity on the T1-weighted images, and mild peripheral enhancement on the delayed dynamic MR images. The peripheral margin of the lesion showed hypointensity on both T1- and T1-weighted images with increased enhancement on the delayed phase images of the dynamic MR images. Conclusion : After percutaneous Holmium-166 injection into rabbit liver parenchyma, the central portion showed liquefactive necrosis, the peripheral portion showed coagulative necrosis with granulation, fibrosis, hemorrhage and depostition of small granules. MR imaging may be helpful in evaluation of the histological change of the liver after percutaneous Holmium-166 treatment.

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Tributyltin Induces Adipogenesis and Apoptosis of Rat Thymic Epithelial Cells (Tributyltin에 의한 흰쥐 흉선 내 상피세포의 지방세포 유도와 세포자연사 증가)

  • Lee, Hyo-Jin;Lee, A-Ra;Ahn, Bo-Ram;Jeon, Eun-Je;Jeong, Ye-Ji;Yang, Hyun-Won
    • Development and Reproduction
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    • v.15 no.4
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    • pp.373-383
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    • 2011
  • Tributyltin (TBT) is one of endocrine disrupters which are known as having similar function to sex steroid hormone inducing apoptosis in various tissues of rodents. Recently, it has been reported that TBT induces apoptosis in thymus causing the decreased thymic function, but little is known about the mechanism. To elucidate the mechanism, three-week-old SD female rats were orally administrated with TBT 1, 10, and 25 mg per body weight (kg) and sesame oil as a control for 7 days. On day 8, the thymi were obtained and weighed, and then the number of thymocytes was counted. We also performed H&E staining, TUNEL assay, and Annexin V flow cytometric analysis to examine the apoptosis rates and the structure in the thymus. Next, we investigated the adipogenesis and apoptosis-related mRNA expression levels in the thymi by real-time PCR. The thymic weight and the number of thymocytes were decreased by TBT in a dose-dependent manner. As a result of the H&E staining, the boundary between cortical and medullary area was blurred in the thymi of TBT treated rats compared to those of controls. In the results of TUNEL assay and Annexin V flow cytometric analysis, apoptosis rates in the thymus were increased after TBT treatment. The expression levels of thymic epithelial cell marker genes such as EVA, KGF, AIRE, and IL-7 were significantly decreased in the thymi of TBT treated rats, but $PPAR{\gamma}$, aP2, PEPCK, and CD36 were significantly increased. The expression of $TNF{\alpha}$ and TNFR1 as apoptosis-related genes also was significantly increased after TBT treatment. The present study demonstrates that TBT can increase the expression of adipogenesis and apoptosis-related genes leading to apoptosis in the thymus. These results suggest that the increased adipogenesis of thymus by TBT exposure might induce apoptosis in the thymus resulting in a loss in thymic immune function.

Effects of Melatonin on Preventing Postoperative Intraperitoneal Adhesion Formation in Rats (Rat에서 술후 복강 유착방지에 대한 melatonin의 효과)

  • Lee, Seung-Chan;Kim, Jung-Eun;Kwon, Young-Sam;Jang, Kwang-Ho
    • Journal of Veterinary Clinics
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    • v.23 no.3
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    • pp.230-235
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    • 2006
  • This study was performed in rats to find the minimum dose of melatonin that can effectively prevent the formation of postoperative intraperitoneal adhesions. Forty-two Sprague Dawley male rats were divided into six groups consisting of 7 rats, respectively. After celiotomy, five abrasions of $0.5{\times}1cm$ area were made on the antimesenteric serosal surface of the colon with a scalpel blade. The abdominal cavity was filled with 1 ml of solution containing 1 mg/kg(Mel 1), 3 mg/kg(Mel 3), 10 mg/kg(Mel 10), 30 mg/kg(Mel 30) and 5% ethanol solution(sham) through the catheter, using a sterile syringe before abdominal closure. Control group was given no adjuvant. The locations and values of adhesion were assessed through the second operation on the 14th day after the first operation. The adhesions were located on serosa to mesentery(54 of 210, 25.7%), serosa to serosa(44 of 210, 21%), serosa to omentum (12 of 210, 5.7%) and serosa to parietal peritoneum(0 of 210, 0%). The incidences of adhesion in Control, Sham, Mel 1, Mel 3, Mel 10 and Mel 30 were 68.6%, 91.4%, 57.1%, 60.1%, 17.1% and 20%, respectively. The values of adhesion separation in Mel 10 and Mel 30 group were lower than those in other groups. However, there was no significant(p<0.05) between Mel 10 and Mel 30 group. This study showed that 10 mg/kg of melatonin were effective in reducing the intraperitoneal adhesion.