• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1236-1251
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• 1998

Background : TNF-$\alpha$ appears to be a central mediator of the host response to sepsis. While TNF-$\alpha$ is mainly considered a proinflammatory cytokine, it can also act as a direct cytotoxic cytokine. However, there are not so many studies about the relationship bet ween TNF-$\alpha$ level and lung injury severity in ALI, particularly regarding the case of ALI caused by direct lung injury such as diffuse pulmonary infection. Recently, a natural defense mechanism, known as the stress response or the heat shock response, has been reported in cellular or tissue injury reaction. There are a number of reports examining the protective role of pre-induced heat stress proteins on subsequent LPS-induced TNF-$\alpha$ release from monocyte or macrophage and also on subsequent LPS-induced ALI in animals. However it is not well established whether the stress protein synthesis such as HSP can be induced from rat alveolar macrophages by in vitro or in vivo LPS stimulation. Methods : We measured the level of TNF-$\alpha$, the percentage of inflammatory cells in bronchoalveolar lavage fluid, protein synthesis in alveolar macrophages isolated from rats at 1, 2, 3, 4, 6, 12, and 24 hours after intratracheal LPS instillation. We performed histologic examination and also obtained histologic lung injury index score in lungs from other rats at 1, 2, 3, 4, 6, 12, 24 h after intratracheal LPS instillation. Isolated non-stimulated macrophages were incubated for 2 h with different concentration of LPS (0, 1, 10, 100 ng/ml, 1, or 10 ${\mu}g/ml$). Other non-stimulated macrophages were exposed at $43^{\circ}C$ for 15 min, then returned to at $37^{\circ}C$ in 5% CO2-95% for 1 hour, and then incubated for 2 h with LPS (0, 1, 10, 100ng/ml, 1, or 10 ${\mu}g/ml$). Results : TNF-$\alpha$ levels began to increase significantly at 1 h, reached a peak at 3 h (P<0.0001), began to decrease at 6 h, and returned to control level at 12 h after LPS instillation. The percentage of inflammatory cells (neutrophils and alveolar macrophages) began to change significantly at 2 h, reached a peak at 6 h, began to recover but still showed significant change at 12 h, and showed insignificant change at 24 h after LPS instillation compared with the normal control. After LPS instillation, the score of histologic lung injury index reached a maximum value at 6 h and remained steady for 24 hours. 35 kDa protein band was newly synthesized in alveolar macrophage from 1 hour on for 24 hours after LPS instillation. Inducible heat stress protein 72 was not found in any alveolar macrophages obtained from rats after LPS instillation. TNF-$\alpha$ levels in supernatants of LPS-stimulated macro phages were significantly higher than those of non-stimulated macrophages(p<0.05). Following LPS stimulation, TNF-$\alpha$ levels in supernatants were significantly lower after heat treatment than in those without heat treatment (p<0.05). The inducible heat stress protein 72 was not found at any concentrations of LPS stimulation. Whereas the 35 kDa protein band was exclusively found at dose of LPS of 10 ${\mu}g/ml$. Conclusion : TNF-$\alpha$ has a direct or indirect close relationship with lung injury severity in acute lung injury or acute respiratory distress syndrome. In vivo and in vitro LPS stimulation dose not induce heat stress protein 72 in alveolar macrophages. It is likely that 35 kDa protein, synthesized by alveolar macrophage after LPS instillation, does not have a defense role in acute lung injury.

• Tuberculosis and Respiratory Diseases
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• v.49 no.6
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• pp.691-702
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• 2000

Background : Acute lung injury (ALI) is a commonly encountered respiratory disease and its prognosis is poor when the treatment is not provided promptly and properly. However no specific pharmacologic treatment is currently available for ALI, although recently several supportive drugs have been under scrutiny. We studied anti-inflammatory effects of pentoxifylline (PF), a methylated xanthine, and ONO-5046, a synthetic neutrophil elastase inhibitor on lipopolysaccharide (LPS)-induced ALI in vitro. Methods : To establish an in vitro model of LPS-induced ALI, primary rat alveolar macrophages and peripheral neutrophils in various ratios (1:0, 5:1, 1:1, 1:5, 0:1) were co-cultured with transformed rat alveolar epithelial cells (L2 cell line) or vascular endothelial cells (IP2-E4 cell line) under LPS stimulation. Each experiment was divided into five groups-control, LPS, LPS+PF, LPS+ONO, and LPS+PF+ONO. We compared LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils in various ratios, and the resultant cytotoxicity on L2 cells or IP2-E4 cells between groups. In addition we also compared the productions of tumor necrosis factor (TNF)-$\alpha$ interleukin (IL)-$1{\beta}$, monocyte chemotactic protein(MCP)-1, IL-6, and IL-10 as well as mRNA expressions of TNF-$\alpha$ inducible nitric oxide synthetase(iNOS), and MCP-1 from LPS-stimulated primary rat alveolar macrophages between groups. Results : (1) PF and ONO-5046 in each or both showed a trend to suppress LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils regardless of their ratio, except for the LPS+PF+ONO group with the 1:5 ratio, although statistical significance was limited to a few selected experimental conditions. (2) PF and ONO-5046 in each or both showed a trend to prevent IP2-E4 cells from LPS-induced cytotoxicity by primary rat alveolar macrophages and peripheral neutrophils regardless their ratio, although statistical significance was limited to a few selected experimental conditions. the effects of PF and/or ONO-5046 on LPS-induced L2 cell cytotoxicity varied according to experimental conditions. (3) PF showed a trend to inhibit LPS-induced productions of INF-$\alpha$ MCP-1, and IL-10 from primary rat alveolar macrophages. ONO-5046 alone didnot affect the LPS-induced productions of proinflammatory cytokines from primary rat alveolar macrophages but the combination of PF and ONO-5046 showed a trend to suppress LPS-induced productions of INF-$\alpha$ and IL-10 PF and ONO-5046 in each or both showed a trend to increase LPS-induced IL-$\beta$ and IL-6 productions from primary rat alveolar macrophages. (4) PF and ONO-5046 in each or both showed a trend to attenuate LPS-induced mRNA expressions of TNF-$\alpha$ and MCP-1 from primary rat alveolar macrophages but at the same time showed a trend increase iNOS mRNA expression. Conclusion : These results suggest that PF and ONO-5046 may play a role in attenuating inflammation in LPS-induced ALI and that further study is needed to use these drugs as a new supportive therapeutic strategy for ALI.

• Korean Journal of Agricultural Science
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• v.5 no.2
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• pp.93-114
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• 1978

The purpose of the study was to find out possible ways for increasing farm income through the sheep and Korean native goats farming, and to investigate meat productivity, wool productivity; woolskin utility, physiological characteristics and correlation between economical college animal farm of the Chungnam National University and sample farms in the suburbs of Dae jeon City were selected for feeding 20 heads of Corriedale wethers and another 20 heads Korean native kids as research materials for the periods of 5th May-26th November, 1977. The data such as growth rate, carcass, viscera weight, blood picture and plamsa components, hebage intake and economic traits were obtained and analysed. The result of the study are summarized as follows: 1. Meat production and quality 1) After 196days of feeding, the body weight of sheep and Korean native goats was increased by two times of those at the beginning of the trial, i.e. 20kg and 8kg respectively. 2) There was no significance of growth rates of sheep in housing and grazing. 3) The growth rate of Korean native goats were excellent at the mountainous areas of Gong ju-Gun where infectious diseases were not found 4) Accroding to the body measurements of 18-month-old sheep, percentages of hip height, body length, rump length, chest depth, chest width, hip width, chest girth and forearm circumference to the withers height were 103,%, 104%, 33%, 44%, 31%, 23%, 135% and 15% respectively, and those of hip height, body length, chest depth and chest girth of 8-month-old native goats to the withers height were 106%, 109%, 46% and 122,% respecitively. As a result, it was found that the percentage of hip height, body length and chest depth of Korean native goats were higher than those of sheep while that of the chest girth of goats was lower. 5) In the carcass data, 47, $52{\pm}2.27%$ of carcass percentage, $34.61{\pm}1.62%$ of lean meat, $26.07{\pm}2.51%$ of viscera, $9.75{\pm}1.4%$ of bone, and $20.95%{\pm}2.14%$ of woolskin for sheep, and $45.58{\pm}5.63%$ of carcass percentage, $27.62{\p}3.81%$ of meat, $34.86{\pm}4.16%$ of viscera, $11.66{\pm}1.83%$ of bone, $3.63{\pm}1.61%$ of skull and $9.26{\pm}2.41%$ of woolskin for native goats were obtained. 6) The contents of moisture, crude protein, crude fat and crude ash in native goat meat were much similar in both plots of housing and grazing. It was, however, known that the contents of moisture and protein were higher in grazinrg than in housing, while fat content was lower in grazing plots. 7) The weights of visceral organs shown similar tendency for both of sheep and native goats. For the weights of liver, heart, kidney and spleen, significance was not reconized among the treatments. Those of rumen, reticulum, small and large intestine were heavier in grazing than in housing, while the amount of visceral fat was heavier in housing. 2. Wool productivity and woolskin 1) The wool production of sheep for 7 months was $3.88{\pm}1.02kg$, and wool percentage, staple length, straighten length, wool growth per day and number of crimps were $9.27{\pm}1.48%$, 8. $47{\pm}1.00cm$, $10.63{\pm}0.99cm$, $0.40{\pm}0.04cm$ and $2.78{\pm}0.40$ respecitively. 2) The tensile strength and tear strength of woolskin treated by alum tanning were highest on the skin obtained from rump, i.e. $1,351kg/mm^2$ and $2,252kg/mm^2$ respectively, and they are in order of loin and shoulder. 3. Utilization and improvement of pasture. 1) The difference of herbage intake of native goats was not recognized between grazing and tethering, but the intake in the afternoon was s lightly higher than that in the morning. However the hervage intake of sheep was superior in grazing and in the afternoon. 2) The cultivation effect was lower in the native goat plots due to their cultivation abilities, in other words, the establishment rates of pasture by hoof cultivation were 60.25% in the goat plots and 77.35% in the sheep plots. 4. Correlation among economical traits. 1) The correlation between live weight of sheep and daily gain was higher. On the other hand, the correlation between other traits was not significant except that live weight, daily gain and lean meat percentage to the length of thoracic vertebrae. The live weight of native goats and meat production were highly correlated, and high correlation was also found between weights of carcass and meat. However, negative correlation was shown between viscera weight and live weight as well as daily gain. 2) The correlatoin between fleece weight of sheep and other traits such as live weight, daily gain and fleece percentage is very high at the 1% siginficant level, and this means that rapid-growth individuals can produce much fleece. 3) The correlation between the factors such as weights of live body, lean meat and viscera of sheep and body measurements, i. e. chest girth and body length was highest, and weights, of carcass and lean meat was highly correlated to chest width and depth. It will be therefore reasonable that the meat productivity estimates will have to be made on the basis of chest girth and body length. The meat production traits of native goats were highly correlated to the most of body measurement data, and the correlation coefficient between chest girth and weights of live body, carcass, lean meat and bone percentage was very high, i. e. 0.992-0.974 in particular. The correlations of meat production traits to chest depth, forearm circumference, body length were 0.759-0.911, 0.759-0.909 and 0.708-0.872 respectively. Therefore, the meat production of native goats will have to be estimated on the basis of chest data. 5. Blood picture and plasma components. 1) The number of erythrocyte and MCHC of native goats were $12.93{\times}10^6/mm^3$ and 36.14%, and those of sheep were $10.68{\times}10^6/mm^3$ and 36.26 respectively. The values of native goats were significantly higher than those of sheep. 2) The hemoglobin concentration, PVC, MCV and MCR of native goats were 10.92 g/100ml, $23.40{\mu}^3$ and 10.94 pg, and those of sheep were 11.73 g/100ml, 36.25 ml/100ml, $33.97{\mu}^3$ and 30.2 ml/100ml 8.43 pg respectively. The values of native goats were significantly lower those of sheep. 3) The number of leukocytes of native goats was significantly higher than that of sheep, that is, $11.64{\times}10^3/mm^3$ in native goats and $9.32{\times}10^3/mm^3$ in sheep. 4) In differential count of leukocyte, neutrophil was significantly high in native goats while lympocyte in sheep. On the other hand, the basophil, eosinophil and monocyte were not significant between native goats and sheep. 5) The amounts of total protein and glucose in the plasma of native goats were 6.2g/100ml and 53.6mg/100ml, and those of sheep were 5.6g/100ml and 45.7mg/100ml, which means that the values of native goats were significantly higher that those of sheep. The amount of total-lipid of native goats(127.6mg/100ml) was significantly than that of sheep(149.6mg/100ml). 6) The amount of non-protein nitrogen, cholesterol, Ca, P, K, Na and Cl were not different between native goats and sheep. 6. Economic analysis. 1) The gross revenue of a farm which fed native goats and sheep was 4,000won per head and the optimum size for feeding them in a farm as a subsidiary work is 5-10 heads. 2) Since there was no difference between housing and grazing, they can be fed in group for farm's subsidiary work. 3) They can be also fed by youths and house wives in the suburbs of cities, because labour requirement is estimated as only two hours per days for feeding 5 heads of native goats and sheep.