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The study for the roles of intratracheally administered histamine in the neutrophil-mediated acute lung injury in rats: (호중구를 매개하는 백서의 급성 폐손상의 병리가전에 있어 기도내로 투여한 히스타민의 역활에 관하여)

  • Koh, Youn-Suck;Hybertson, Brooks M.;Jepson, Eric K.;Kim, Mi-Jung;Lee, In-Chul;Lim, Chae-Man;Lee, Sang-Do;Kim, Dong-Soon;Kim, Won-Dong;Repine, John E.
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.3
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    • pp.308-322
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    • 1996
  • Background : Neutrophils are considered to play critical roles in the development of acute respiratory distress syndrome. Histamine, which is distributed abundantly in lung tissue, increases the rolling of neutrophills via increase of P-selectin expression on the surface of endothelial cells and is known to have some interrelationships with IL-1, IL-8 and TNF-$\alpha$. We studied to investigate the effect of the histamine on the acute lung injury of the rats induced by intratracheal insufflation of TNF-$\alpha$ which has less potency to cause lung injury compared to IL-1 in rats. Methods : We intratracheally instilled saline or TNF(R&D, 500ng), IL-1(R&D, 50ng)or histamine of varius dose(1.1, 11 and $55\;{\mu}g/kg$) with and without TNF separately in Sprague-Dawley rats weighing 270-370 grams. We also intratracheally treated IL-1(50ng) along with histamine($55\;{\mu}g/kg$). In cases, there were synergistic effects induced by histamine on the parameters of TNF-induced acute lung injury, antihistamines(Sigma, mepyramine as a $H_1$ receptor blockade and ranitidine as a $H_2$ receptor blockade, 10 mg/kg in each)were co-administered intravenously to the rats treated TNF along with histamine($1.1\;{\mu}g/kg$) intratraeheally. Then after 5 h we measured lung lavage neutrophil numbers, lavage cytokine-induced neutrophil chemoattractants(CINC), lung myeloperoxidase activity(MPO) and lung leak. We also intratracheally insufflated TNF with/without histamine($11\;{\mu}g/kg$), then after 24 h measured lung leak in rats. Statistical analyses were done by Kruskal-Wallis nonparametric ANOVA test with Dunn's multiple comparison test or by Mann-Whitney U test. Results : We found that rats given TNF, histamine alone(11 and $55\;{\mu}g/kg$), and TNF with histamine(l.1, 11, and $55\;{\mu}g/kg$) intratracheally had increased (p<0.05) lung MPO activity compared with saline-treated control rats. TNF with histamine $11\;{\mu}g/kg$ had increased MPO activity (P=0.0251) compared with TNF-treated rats. TNF and TNF with histamine(1.1, 11, and $55\;{\mu}g/kg$) intratracheally had all increased (p<0.05) lung leak, lavage neutophil numbers and lavage CINC activities compared with saline. TNF with histamine $1.1\;{\mu}g/kg$ had increased (p=0.0367) lavage neutrophil numbers compared with TNF treated rats. But there were no additive effect of histamine with TNF compared with TNF alone in acute lung leak on 5 h and 24 h in rats. Treatment of rats with the $H_1$ and $H_2$ antagonists resulted in inhibitions of lavage neutrophil accumulations and lavage CINC activity elevations elicited by co-treated histamine in TNF-induced acute lung injury intratracheally in rats. We also found that rats given IL-1 along with histamine intratracheally did not have increase in lung leak compared with IL-1 treated rats. Conclusion : Histamine administered intratracheally did not have synergistic effects on TNF-induced acute lung leak inspite of additive effects on increase in MPO activity and lavage neutrophil numbers in rats. These observations suggest that instilling histamine intratracheally would not play synergistic roles in neutrophil-mediated acute lung injury in rats.

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Genetic Polymorphisms of the $\beta_2$-Adrenergic Receptor in the Severity of Bronchial Asthma (기관지 천식 환자에서 천식 증상의 정도에 따른 $\beta_2$ 교감신경 수용체의 유전자 다형성)

  • Shim, Jae-Jeong;Kim, Jei-Hyung;Lee, Seung-Yong;Kwan, Young-Hwan;Lee, So-Ra;Lee, Sang-Youb;Kang, Se-Yong;Kang, Yong-Koo;Cho, Jae-Youn;In, Kwang-Ho;Won, Nam-Hee;Yoo, Se-Hwa;Kang, Kyung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.1
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    • pp.77-89
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    • 1998
  • Background: Genetic and environmental factors are known to affect the incidence and severity of asthma. Stimulation of $\beta_2$-Adrenergic Receptor ($\beta_2$AR) results in smooth muscle relaxation, leading to decrease in resistance of airflow. The gene encoding the $\beta_2$AR has recently been seguenced. The $\beta_2$AR genotype at the polymorphic loci of codons 16, 27, 34, and 164 was known to cause changes in the amino acids. The relationships between the structure of the $\beta_2$AR and its functions are being elucidated. Purpose : The gene encoding the $\beta_2$AR was carried out to assess the frequency of polymorphisms in bronchial asthma, to determine wheather these polymorphisms have any relation to the severity, or nocturnal symptoms in bronchial asthma. Methods: The subjects studied were 103 patients with bronchial asthma, which consisted of 30 mild episodic, 32 mild persistent, 17 moderate, and 24 severe asthma patients. The polymorphisms of the $\beta_2$AR gene were detected by mutated allele specific amplification (MASA) method at the codons 16,27,34, and 164. Results: The most frequent polymorphism was arginine 16 to glycine. The other two polymorphisms, valine 34 to methionine and glutamine 27 to glutamic acid occured in 11 and 6 patients respectively. The polymorphism of threonine 164 to isoleucine was not found in our enrolled patients. The homozygous polymorphism of $\beta_2$AR gene was found in only arginine 16 to glycine (12.6%). The heterozygous polymorphisms of $\beta_2$AR gene were in arginine 16 to glycine, valine 34 to methionine, and glutamine 27 to glutamic acid, as 65.1 %,10.7%, and 5.8% respectively in asthma patients. The presence of agrginine 16 to glycine heterozygous or/and homozygous polymorphism was associated in severe asthma (p=0.015), but there was no association between the other three polymorphisms and the severity of asthma. The frequency of the $\beta_2$AR gene polymorphisms was no relation in nocturnal asthma as compared with non-nocturnal asthma. Conclusion: The arginine 16 to glycine polymorphism of the $\beta_2$AR gene is the most frequently found in asthma patients and association with severe asthma. But there was no association between the polymorphism of the $\beta_2$AR gene and nocturnal asthma.

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Analysis of Greenhouse Thermal Environment by Model Simulation (시뮬레이션 모형에 의한 온실의 열환경 분석)

  • 서원명;윤용철
    • Journal of Bio-Environment Control
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    • v.5 no.2
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    • pp.215-235
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    • 1996
  • The thermal analysis by mathematical model simulation makes it possible to reasonably predict heating and/or cooling requirements of certain greenhouses located under various geographical and climatic environment. It is another advantages of model simulation technique to be able to make it possible to select appropriate heating system, to set up energy utilization strategy, to schedule seasonal crop pattern, as well as to determine new greenhouse ranges. In this study, the control pattern for greenhouse microclimate is categorized as cooling and heating. Dynamic model was adopted to simulate heating requirements and/or energy conservation effectiveness such as energy saving by night-time thermal curtain, estimation of Heating Degree-Hours(HDH), long time prediction of greenhouse thermal behavior, etc. On the other hand, the cooling effects of ventilation, shading, and pad ||||&|||| fan system were partly analyzed by static model. By the experimental work with small size model greenhouse of 1.2m$\times$2.4m, it was found that cooling the greenhouse by spraying cold water directly on greenhouse cover surface or by recirculating cold water through heat exchangers would be effective in greenhouse summer cooling. The mathematical model developed for greenhouse model simulation is highly applicable because it can reflects various climatic factors like temperature, humidity, beam and diffuse solar radiation, wind velocity, etc. This model was closely verified by various weather data obtained through long period greenhouse experiment. Most of the materials relating with greenhouse heating or cooling components were obtained from model greenhouse simulated mathematically by using typical year(1987) data of Jinju Gyeongnam. But some of the materials relating with greenhouse cooling was obtained by performing model experiments which include analyzing cooling effect of water sprayed directly on greenhouse roof surface. The results are summarized as follows : 1. The heating requirements of model greenhouse were highly related with the minimum temperature set for given greenhouse. The setting temperature at night-time is much more influential on heating energy requirement than that at day-time. Therefore It is highly recommended that night- time setting temperature should be carefully determined and controlled. 2. The HDH data obtained by conventional method were estimated on the basis of considerably long term average weather temperature together with the standard base temperature(usually 18.3$^{\circ}C$). This kind of data can merely be used as a relative comparison criteria about heating load, but is not applicable in the calculation of greenhouse heating requirements because of the limited consideration of climatic factors and inappropriate base temperature. By comparing the HDM data with the results of simulation, it is found that the heating system design by HDH data will probably overshoot the actual heating requirement. 3. The energy saving effect of night-time thermal curtain as well as estimated heating requirement is found to be sensitively related with weather condition: Thermal curtain adopted for simulation showed high effectiveness in energy saving which amounts to more than 50% of annual heating requirement. 4. The ventilation performances doting warm seasons are mainly influenced by air exchange rate even though there are some variations depending on greenhouse structural difference, weather and cropping conditions. For air exchanges above 1 volume per minute, the reduction rate of temperature rise on both types of considered greenhouse becomes modest with the additional increase of ventilation capacity. Therefore the desirable ventilation capacity is assumed to be 1 air change per minute, which is the recommended ventilation rate in common greenhouse. 5. In glass covered greenhouse with full production, under clear weather of 50% RH, and continuous 1 air change per minute, the temperature drop in 50% shaded greenhouse and pad & fan systemed greenhouse is 2.6$^{\circ}C$ and.6.1$^{\circ}C$ respectively. The temperature in control greenhouse under continuous air change at this time was 36.6$^{\circ}C$ which was 5.3$^{\circ}C$ above ambient temperature. As a result the greenhouse temperature can be maintained 3$^{\circ}C$ below ambient temperature. But when RH is 80%, it was impossible to drop greenhouse temperature below ambient temperature because possible temperature reduction by pad ||||&|||| fan system at this time is not more than 2.4$^{\circ}C$. 6. During 3 months of hot summer season if the greenhouse is assumed to be cooled only when greenhouse temperature rise above 27$^{\circ}C$, the relationship between RH of ambient air and greenhouse temperature drop($\Delta$T) was formulated as follows : $\Delta$T= -0.077RH+7.7 7. Time dependent cooling effects performed by operation of each or combination of ventilation, 50% shading, pad & fan of 80% efficiency, were continuously predicted for one typical summer day long. When the greenhouse was cooled only by 1 air change per minute, greenhouse air temperature was 5$^{\circ}C$ above outdoor temperature. Either method alone can not drop greenhouse air temperature below outdoor temperature even under the fully cropped situations. But when both systems were operated together, greenhouse air temperature can be controlled to about 2.0-2.3$^{\circ}C$ below ambient temperature. 8. When the cool water of 6.5-8.5$^{\circ}C$ was sprayed on greenhouse roof surface with the water flow rate of 1.3 liter/min per unit greenhouse floor area, greenhouse air temperature could be dropped down to 16.5-18.$0^{\circ}C$, whlch is about 1$0^{\circ}C$ below the ambient temperature of 26.5-28.$0^{\circ}C$ at that time. The most important thing in cooling greenhouse air effectively with water spray may be obtaining plenty of cool water source like ground water itself or cold water produced by heat-pump. Future work is focused on not only analyzing the feasibility of heat pump operation but also finding the relationships between greenhouse air temperature(T$_{g}$ ), spraying water temperature(T$_{w}$ ), water flow rate(Q), and ambient temperature(T$_{o}$).

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