• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.319-327
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• 1994

Background: The pathogenetic mechanism of adult respiratory distress syndrome(ARDS) is not clearly defined yet, but it is well known that increased pulmonary capillary permeabilty is characteristic feature of ARDS. The increased alveolar-capillary permeability is usually preceded by damage of pulmonary artery endothelial cells. The released enzymes and oxygen free radicals from the activated neutrophils seem to play a predominant role in endothelial cell cytotoxicity. The activated neutrophils, however, probably are not the sole contributing factor in this type of damage because many cases of ARDS have been reported in severe neutropenia. Bacterial endotoxin perse and/or oxygen free radicals released from endothelial cells are suggested to be possible factors that contribute to the development of ARDS. The purpose of this study is to investigate the direct cytotoxicity of endotoxin and the role of oxygen free radicals released from the endothelial cells in endotoxin-induced endothelial cell cytotoxicity. Methods: First, to investigate whether endotoxin is cytotoxic to HUVE by itself, various doses of endotoxin were added to culture medium and cytotoxicity was measured. Second, to evaluate the possible role of oxygen free radical in endotoxin-induced HUVE cytotoxicity, various antioxidants were added on the endotoxin-induced HUVE cytotoxicity and cytotoxicity was measured. Third, to verify the release of oxygen free radicals from HUVE, the concentrations of hydrogen peroxide in the endotoxin-treated culture supernatant were measured. Finally, to observe the cytotoxic effect of hydrogen peroxide, HUVE cytotoxicity in the presence of various doses of hydrogen peroxide was measured. The fourth generations of subcultured HUVE from primary culture were used. The cell cytotoxicity was quantified by the chromium-51 release assay. Results: 1) Endotoxin alone showed HUVE cytotoxicity in a dose-dependent fashion. 2) Endotoxin-induced HUVE cytotoxicity was significantly attenuated by the pretreatment of catalase and DMTU. 3) Hydrogen peroxide was released from HUVE after endotoxin treatment in a dose-dependent fashion. 4) Exogenous hydrogen peroxide also showed HUVE cytotoxicity in a dose-dependent fashion. Conclusion: These results suggest that endotoxin alone can directly injure HUVE, and, oxygen-free radicals released from HUVE in response to endotoxin may also participate in the endotoxin-induced HUVE cytotoxicity.

• The Korean Journal of Physiology
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• v.2 no.2
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• pp.21-31
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• 1968

The appearance rates of antipyrine and urea into cerebrospinal fluid from blood were studied in the rabbits which were in the state of hypotension and of high permeability in the capillary beds following injection of histamine. The alteration in the distribution of electrolytes among various compartments of the brain and the permeability characteristics in the blood-cerebrospinal fluid barrier were also observed. Adult male rabbits, weighing around 2 kg, were used. Twenty four rabbits were divided into 3 groups. Besides the control group, histamine treated rabbits were categorized into 2 groups. $H_1$ consisted of the rabbits showing moderate responses to histamine and ranging from 62 to 80 mmHg in their mean anterial blood pressure. The animals which belong to $H_2-group$ showed severe responses to histamine and the mean anterial blood pressures dropped to 30-50 mmHg. Animals were anesthetized with nembutal, 30mg/kg i.v. The mean arterial blood pressure was read by means of the mercury manometer connected to the femoral artery. The animals, treated with histamine, were kept in hypotensive state at least for 40 minutes before the administration of the test-substances. The test-substances, 300 mg of urea and 200 mg of antipyrine, were dissolved in 3 ml of distilled water and were injected into the ear vein of the rabbit. After 10 minutes elapsed arterial blood sample was taken from the femoral artery and cerebrospinal fluid from the cisterna magna. Brain tissues were also analysed with respect to electrolytes in order to observe the disturbances in the electrolytes balance as well as in the function of the central nervous system. The results obtained were as follow: 1. The ratio of antipyrine concentration in cerebrospinal fluid to that of arterial blood plasma, that was the distribution ratio, was close to unity, revealing a well established equilibrium between the compartments of blood and cerebrospinal fluid in 10 minutes. In other words, there was no diffusion barrier with regard to antipyrine. The ratios over unity which were frequently seen in the histamine treated animals were attributable to the early penetration of the substance into the cerebrospinal fluid. 2. The appearance rates of urea into the cerebrospinal fluid in the histamine treated rabbits were higher in comparison with those of in the control animals. The increasing tendency in the rates was particularly remarkable in the $H_2-group$, showing the enhanced penetration of urea across the boondary. 3. In the htisamine treated $H_2-group$ the concentration of potassium in the blood plasma and cerebrospinal fluid well exceeded the control values and showed 8.5 and 9.0 mEq/l in average, respectively. Simultaneous drops in the brain tissue water were noticed, suggesting the leakage of intracellular potassium. 4. There was a coincidence in the rising pattern of potassium in the blood plasma and in the cerebrospinal fluid of $H_2-group$ and at least partial removal of the blood-cerebrospinal fluid barrier with respect to potassium was suggested in these animals. 5. The concentration of sodium in the blood plasma or in the cerebrospinal fluid showed no significant changes following histamine injection. However, sodium in the brain tissue revealed slight elevation in the histamine treated groups. 6. The ratios of the concentrations of potassium to those of sodium, [K]/[Na] in the brain tissues, were 1.92 in the control 1.82 in the $H_1$ and 1.52 in the $H_2-group$, respectively. The marked drop in the $H_2-group$ might represent neural dysfunction in the extremely hypotensive rabbits.

• Tuberculosis and Respiratory Diseases
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• v.39 no.1
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• pp.42-54
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• 1992

Background:It has been suggested that the cyclooxygenase metabolites play an important role in changes of early hemodynamic parameters in the endotoxin-induced acute lung injury. But there have been many debates about their role in the late increase of alveolar-capillary permeability, and it is not known whether they act directly or indirectly through oxygen free radicals which have been known to be produced during the metabolic process of cyclooxygenase pathway. So we performed this study to identify the pathogenetic role of cyclooxygenase metabolites in the endotoxin-induced acute lung injury in domestic pigs. Method: We infused endotoxin into 8 domestic pigs; endotoxin only (n=3), and pretreatment with indomethacin (n=5). We observed the sequential changes in hemodynamic parameters, the concentration of plasma oxidized glutathione (GSSG) in pulmonary arterial and venous blood, and albumin content in bronchoalveolar lavage fluid (BALF). Results: 1) While cardiac output decreased, mean pulmonary arterial pressure, pulmonary vascular resistance, and alveolar-arterial oxygen difference increased over phase 1 (0-2hr) and phase 2 (2-4.5hr) by endotoxin, indomethacin attenuated the decrease in cardiac output during phase 1 and increase in mean pulmonary arterial pressure, pulmonary vascular resistance, and alveolar-arterial oxygen difference during both phases. 2) The increase in plasma GSSG content during phase 2 was not attenuated by indomethacin. 3) The content of BALF albumin was significantly lower in indomethacin groups than that of endotoxin group. Conclusion: These results suggest that it is likely that cyclooxygenase metabolites have an effect on endotoxin-induced acute lung injury during both phases probably through direct action.

• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.219-229
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• 2002

Background : Sepsis-induced acute lung injury (ALI) is caused by many cellular and humoral mediators induced by an endotoxin. Histamine, which is widely distributed in the lungs and has been considered as an important mediator of sepsis. It increases P-selectin expression on the endothelial cell surfaces and induces IL-8 secretion. Therefore, an endotoxin-induced histamine may be related to neutrophil-mediated ALI by inducing the migration and activation of neutrophils in the lung tissue. However, the role of endogenous histamine in endotoxin ALI has not been clarified. The purpose of this study was to investigate how endotoxin-induced ALI is influenced by endogenous histamine and to identify the possible mechanism of action. Materials and Methods : The study consisted of 4 groups using Sprague-Dawley rats : 1) control group, where the rats were infused intratracheally by normal saline, 2) an endotoxin group, where lipopolysaccharide (LPS) was administered intratracheally 3) the $H_2$ receptor antagonist-treated group ($H_2$ group) and 4) the $H_1$ receptor antagonist-treated group ($H_1$ group), where $H_2$-receptor blocker (ranitidine) and $H_1$-receptor blocker(pyrilamine) were co-treated intravenously with the intratracheal administration of an endotoxin. The lung leak index using $I^{125}$-BSA, the total protein and LDH concentration in the lung lavage fluid, myeloperoxidase(MPO) activity in the lung tissue, the pathologic score and the total number of neutrophils, TNF-$\alpha$, IL-$1{\beta}$ and IL-10 in lung lavage (BAL) fluid were measured in each group as the indices of lung injury. Results : Compared to the control group, the endotoxin group exhibited significant increases in all lung injury indices. Significant reductions in the endotoxin-mediated increases in lung leak index (p<0.05) were observed in both the $H_1$ and $H_2$ groups. In addition the total protein (p<0.05) and LDH concentration (p<0.05) in the BAL fluid were also lower in the $H_2$ group compared to the endotoxin group. However, there was no change in the MPO activity in the lung tissue, the pathologic score and the total number of neutrophils in the BAL fluid in both the $H_2$ and $H_1$ groups compared to the endotoxin group. The increases in TNF-$\alpha$ IL-$1{\beta}$ and IL-10 concentrations in the BAL fluid observed in the endotoxin group were not reduced in the $H_2$ and $H_1$ groups. Conclusion : Antihistamine attenuated the enhanced alveolar-capillary permeability induced by the endotoxin via the $H_2$ receptor. However the attenuating mechanism may not be related to the pathogenesis of neutrophil dependent lung injury.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.9
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• pp.1154-1161
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• 2008

The purpose of this study is to determine the possibility of using Sophorae fructus as natural health food source. To accomplish this purpose, the contents of general and antioxidative nutrients of Sophora fructus were measured. The contents of carbohydrate, crude protein, crude lipid and ash are 75.9%, 16.4%, 2.41%, and 5.2%, respectively, while the calories of Sophora fructus was 337.3 kcal. Total dietary fiber was 15.07% of total carbohydrates. The percentages of water soluble dietary fiber to insoluble dietary fiber were 1.09% and 10.36%, respectively. The protein was composed of a total of 18 different kinds of amino acids. The contents of essential and non-essential amino acids were 2,310.91 mg and 5,218.52 mg. The K was the largest mineral followed by Ca, P and Mg, which means Sophorae fructus is alkali material. The contents of saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids were 24.94%, 32.40%, and 32.86%, respectively. Therefore, the amount of the total unsaturated fatty acid was higher than that of any other plant. The content of vitamin C in Sophorae fructus was higher than that of any other plant, which suggests that it could increase blood elasticity. The content of rutin, which is responsible for capillary vessel permeability, was 1.78%. The contents of water soluble antioxidative materials in 1 mL of water-extracted Sophorae fructus were $4.95\;{\mu}g$ which is comparable to 1,560.96 mmol of vitamin C in antioxidant effect. The general nutrients and other antioxidatant bioactive materials in Sophorae fructus were also potential materials for good health food. It is expected that a follow up study on Sophorae fructus through developing processed food and evaluation of their functional properties would provide useful information as a source of medicinal foods.

• Tuberculosis and Respiratory Diseases
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• v.54 no.1
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• pp.91-103
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• 2003

Background : Histamine is widely distributed in the lung. It increases capillary permeability and the P-selectin expression on vascular endothelial cell surfaces. We studied the role of endogenous histamine on the pathogenesis of endotoxin-induced acute lung injury (ALI) in rats. Methods: We instilled either normal saline (control group) or lipopolysaccharide (3 mg/Kg, LPS group) to tracheas of Sprague-Dawley rats. H1-receptor blocker (mepyramine, 10 mg/Kg, H1RB group), H2-receptor blocker (ranitidine, 10 mg/Kg, H2RB group), and H3-receptor blocker (thioperamide, 2 mg/Kg, H3RB group) were administered through vein or peritoneum along with intratracheal LPS administration. Statistical significance was accepted at p<0.05. Results : LPS increases the histamine level in BAL fluid significantly at 2 h after the treatment compared with control group. LPS significantly increases protein concentration, PMN cell count in bronchoalveolar lavage (BAL) fluid, and myeloperoxidase (MPO) activity in the lung tissue at 6 h compared to control group. PMN cell count in BAL fluid and MPO activity in lung tissue were significantly lower in H2RB-group compared to LPS-group. However, protein concentration in BAL fluid showed no significant differences between the LPS alone and LPS with histamine receptor blockade. Conclusions : Endogenous histamine might be involved in the recruitment of PMNs in LPS-induced ALI via H2 receptor. However, its role in ALI would not be significant in this model.

• Tuberculosis and Respiratory Diseases
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• v.57 no.1
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• pp.37-46
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• 2004

Background : Lung pericytes are important constituent cells of blood-air barrier in pulmonary microvasculature. These cells take part in the control of vascular contractility and permeability. In this study, it was hypothesized that change of lung pericytes might be attributable to pathologic change in microvasculature in acute lung injury. The purpose of this study was how hypoxia change proliferation and genetic expression in lung pericytes. Methods : From the lungs of several Sprague-Dawley rats, performed the primary culture of lung pericytes and subculture. Characteristics of lung pericytes were confirmed with stellate shape in light microscopy and immunocytochemistry. 2% concentration of oxygen and $200{\mu}M$ $CoCl_2$ were treated to cells. Tryphan blue method and reverse transcription-polymerase chain reaction were done. Results : 1. We established methodology for primary culture of lung pericytes. 2. Hypoxia inhibited cellular proliferation in pericytes. 3. Hypoxia could markedly induce vascular endothelial growth factor(VEGF) and smad-2. 4. Hypoxia-inducible factor-$1{\alpha}$(HIF-$1{\alpha}$) was also induced by 2% oxygen. Conclusion : Viability of lung pericytes are inhibited by hypoxia. Hypoxia can stimulate expression of hypoxia-responsive genes. Pericytic change may be contributed to dysfunction of alveolar-capillary barrier in various pulmonary disorders.

• Tuberculosis and Respiratory Diseases
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• v.56 no.1
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• pp.77-84
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• 2004

Background : We hypothesized that there was a relationship between body weight change and bronchodilator response (BDR) in patients with chronic renal failure (CRF) on hemodialysis (HD). Several mechanisms such as pulmonary edema due to water retention or increased permeability of alveolar capillary may play a important role in pulmonary function impairment and bronchial hyperresponsiveness in patients with CRF on HD. But, no studies have been published concerning BDR in patients with CRF on HD. This study was aimed to know the immediate effect of hemodialysis on pulmonary function and BDR in patients with CRF on HD. Methods : This study included 30 patients with CRF on HD. We collected data including age, sex, height, pretibial and pedal pitting edema, interdialysis weight gain, postdialysis weight loss, underlying diseases, duration of HD, $FEV_1$, FVC, $FEV_1/FVC$, and BDR before and after HD. Results : Interdialysis weight gain of the patients was $3.4{\pm}1.0kg$, and postdialysis weight loss was $3.2{\pm}0.7kg$. Before HD,$FEV_1$, FVC, and $FEV_1/FVC$ of the patients were $89{\pm}22%$, $86{\pm}19%$ of predicted, and $87{\pm}10%$. After bronchodilator inhalation, these parameters were changed to $95{\pm}22%$, $90{\pm}19%$ of predicted, and $88{\pm}9%$ respectively. BDR was positive in 15 patients. After HD, $FEV_1$, FVC, and $FEV_1/FVC$ of the patients were $100{\pm}23%$, $94{\pm}18%$ of predicted, and $88{\pm}11%$. After bronchodilator inhalation, these parameters were changed to $102{\pm}23%$, $96{\pm}18%$ of predicted, and $89{\pm}8%$ respectively. BDR was positive in 9 patients. Conclusion : First, HD increases $FEV_1$, FVC, and $FEV_1/FVC$ but little affects BDR. Second, there is no correlation between postdialysis weight loss and increases in $FEV_1$, FVC, and $FEV_1/FVC$ after HD. Third, there is also no correlation not only between interdialysis weight gain and BDR before HD but between postdialysis weight loss and BDR after HD.