• Tuberculosis and Respiratory Diseases
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• v.40 no.4
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• pp.357-366
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• 1993

Background: Lung clearance of inhaled $^{99m}Tc$-DTPA reflects alveolar epithelial permeability and it had been reported as more sensitive than conventional pulmonary function tests in detecting lung epithelial damage. However, measuring lung clearance of inhaled $^{99m}Tc$-DTPA by gamma camera may not always reflect alveolar epithelial permeability exactly because it is influenced by mucociliary clearance depending on the site of particle deposition. Moreover, this method takes much time and patient's effort because he has to sit or lie still in front of the camera for a prolonged period. Most of the absorbed DTPA is excreted in urine within 24 hours and the amount of excreted DTPA in urine during the first few hours after inhalation is influenced by absorption rate which is correlated with the alveolar-epithelial permeability suggesting that the urinary excretion, especially in first few hours, may be an alternate index for lung clearance. The purpose of this study was to evaluate the usefulness of ratio of excreted $^{99m}Tc$-DTPA in 2 hour and 24 hour urine as an index of alveolar-epithelial damage. Methods: Pulmonary function tests including diffusing capacity and lung clearance of $^{99m}Tc$-DTPA measured by gama camera ($T_{1/2}$) and 2hr/24hr urine excretion ratio (Ratio) of inhaled $^{99m}Tc$-DTPA in 8 normal subjects and 14 patients with diffuse interstitial lung disease were compared. Results: 1) In the normal control, there was significant negative correlation between the $T_{1/2}$ and the Ratio (r=-0.77, p<0.05). In patients with diffuse interstitial lung disease, there also was significant negative correlation between $T_{1/2}$ and Ratio(r=-0.63, p<0.05). 2) In diffuse interstitial lung disease patients, the $T_{1/2}$ was $38.65{\pm}11.63$ min which was significantly lower than that of normal control, $55.53{\pm}11.15$ min and the Ratio was $52.15{\pm}10.07%$ also signifantly higher than that of the normal control, $40.43{\pm}5.53%$ (p<0.05). 3) There was no significant correlations between $T_{1/2}$ or Ratio and diffusing capactiy of lung in both patients and controls (p>0.05). Conclusion: These results suggests that 2hr/24hr urine excretion ratio of inhaled $^{99m}Tc$-DTPA is a useful simple bedside test in assessing alveolar epithelial permeability and that it may be used as an additive follow-up test in patients with diffuse interstitial lung disease complementing conventional pulmonary function tests.

• The Korean Journal of Nuclear Medicine
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• v.28 no.3
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• pp.338-342
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• 1994

Pulmonary clearance of Tc-99m-DTPA(PCD) has been used for the measurement of polmonary epithelial permeability. It has been reported to be increased not only in variety of polmonary diseases including ARDS, interstitial fibrosis, and smokers, but also in normal subjects on positive end expiratory pressure respirator, or after exercise. It was also noted that decrease of pulmonary blood flow due to pulmonary arterial obstruction results in delayed PCD. Normal range of PCD varies with institutes. We prospectively measured PCD in 17 normals (5 males and 12 females) consisted of staffs and trainees in the department of radiology of Kangnam St. Mary's hospital using original Bark Nebulizer (India). Age ranged from 32 to 43 years. 370 MBq of Tc-99m-DTPA was inhaled in supine position and supine posterior images were subsequently obtained with 1 min/frame, $64{\times}64$ matrix and word mode for 30min. Regions of interest were set on each lung, whole lungs, and upper, middle and lower thirds of right lung, respectively. Best fit regression curve was obtained by least square method from initial 7min after peak activity on each curve and time for half clearance of maximum activity (t1/2) was calculated. Mean t1/2 was $51{\pm}11.2min$ for whole lung. There was no significant difference between t1/ 2 of right and left lungs. Initial uptake was higher in the lower third and t1/2 was shorter in the lower third than in the upper third(P<0.05). We reviewed several reports on PCD and compared our data with the others. In this study, faster clearance in the lower third may be due to the position imaged with or the environment the subjects belong to, and further investigation is under way.

• The Korean Journal of Nuclear Medicine
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• v.32 no.3
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• pp.266-275
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• 1998

Purpose: We measured pulmonary epithelial permeability by $^{99m}Tc-DTPA$ radioaerosol clearance in patients with diabetes and correlated with the presence of microangiopathy to understand the pathophysiology of pulmonary microangiopathy and evaluate $^{99m}Tc-DTPA$ radioaerosol clearance as a diagnostic test to assess pulmonary microangiopathy. Materials and Methods: We performed $^{99m}Tc-DTPA$ radioaerosol scan in 10 normal subjects, 10 asymptomatic smokers, 20 diabetic patients without history of smoking (10 with microangiopathy, 10 without microangiopathy). $^{99m}Tc-DTPA$ clearance half-time ($T_{1/2}$) was calculated, then compared with the result of chest radiography and pulmonary function test. Results: Chest radiography and pulmonary function test were normal in all subjects. There were no significant difference of clinical or laboratory characteristics between these groups except age. The diabetic patients with microangiopathy were significantly older (p<0.05). The $T_{1/2}$ of normal subjects and asymptomatic smokers were significantly different ($65.2{\pm}23.7min$ vs $39.6{\pm}9.8min$, p<0.05). For diabetic patients with microangiopathy, the $T_{1/2}$ was $90.5{\pm}46.5min$ and significantly delayed when compared with those of normals and asymptomatic smokers (p<0.05). However, the $T_{1/2}$ of diabetic patients without microangiopathy, $70.0{\pm}12.7min$, was not significantly different from those of normals or asymptomatic smokers (p>0.05). No significant correlation was found between the $T_{1/2}$ and spirometric parameters including DLco, FVC, $FEV_1,\;FEV_1/FVC$ (%) and $FEF_{25-75%}$ in all subjects, and between the $T_{1/2}$ and duration of diabetes ;in diabetic patients. Conclusion: Eventhough the influence of age can't be excluded, delayed $^{99m}Tc-DTPA$ clearance half-time ($T_{1/2}$) in diabetic patients with microangiopathy indicates decreased pulmonary capillary permeability as one of the pathophysiologic results of pulmonary microangiopaththy. Further studies are needed in larger number of age matched control and diabetic patients to evaluate the diagnostic efficacy.

• Tuberculosis and Respiratory Diseases
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• v.40 no.3
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• pp.236-249
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• 1993

Background: Among the injurious agents to which the lung airspaces are constantly exposed are reactive species of oxygen. It has been widely believed that reactive oxygen species may be implicated in the etiology of lung injuries. In order to elucidated how this oxidant causes lung cell injury, we investigated the effects of exogenous $H_2O_2$ on alveolar epithelial barrier characteristics. Methods: Rat type II alveolar epithelial cells were plated onto tissue culture-treated polycarbonate membrane filters. The resulting confluent monolayers on days 3 and 4 were mounted in a modified Ussing chamber and bathed on both sides with HEPES-buffered Ringer solution. The changes in short-circuit current (Isc) and monolayer resistance (R) in response to the exogenous hydroperoxide were measured. To determine the degree of cellular catalase participation in protection against $H_2O_2$ injury to the barrier, experiments were repeated in the presence of 20 mM aminotriazole (ATAZ, an inhibitor of catalase) in the same bathing fluid as the hydroperoxide. Results: These monolayers have a high transepithelial resistance (>2000 ohm-$cm^2$) and actively transport $Na^+$ from apical fluid. $H_2O_2$(0-100 mM) was then delivered to either apical or basolateral fluid. Resulting indicated that $H_2O_2$ decreased Isc and R gradually in dose-dependent manner. The effective concentration of apical $H_2O_2$ at which Isc (or R) was decreased by 50% at one hour ($ED_{50}$) was about 4 mM. However, basolateral $H_2O_2$ exposure led to $ED_{50}$ for Isc (and R) of about 0.04 mM. Inhibition of cellular catalase yielded $ED_{50}$ for Isc (and R) of about 0.4 mM when $H_2O_2$ was given apically, while $ED_{50}$ for basolateral exposure to $H_2O_2$ did not change in the presence of ATAZ. The rate of $H_2O_2$ consumption in apical and basolateral bathing fluids was the same, while cellualr catalase activity rose gradually with time in culture. Conclusion: Our data suggest that basolateral $H_2O_2$ may affect directly membrane component (e.g., $Na^+,\;K^+$-ATPase) located on the basolateral cell surface. Apical $H_2O_2$, on the other hand, may be largely degraded by catalase as it passes through the cells before reaching these membrane components. We conclude that alveolar epithelial barrier integrity as measured by Isc and R are compromised by $H_2O_2$ being relatively sensitive to basolateral (and insensitive to apical) $H_2O_2$.

• Journal of Environmental Health Sciences
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• v.39 no.1
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• pp.48-55
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• 2013

Objective: The use of nanoparticle products is expected to present a potential harmful effect on consumers. Also, the lack of information regarding inhaled nanoparticles may pose a serious problem. In this study, we addressed this issue by studying pulmonary toxicity after nasal instillation of Al-NPs in SD rats. Methods: The animals were exposed to Al-NPs at 1 mg/kg body weight (low dose), 20 mg/kg body weight (medium dose) and 40 mg/kg body weight (high dose). To determine pulmonary toxicity, bronchoalveolar lavage (ts.AnBAL) fluid analysis and histopathological examination were conducted in rats. In addition, cell viability was investigated at 24 hours after the treatment with Al-NPs. Results: BAL fluid analysis showed that total cells (TC) count and total protein (TP) concentrations increased significantly in all treatment groups, approximately two to three times. Also, lactate dehydrogenase (LDH) and cytokines such as TNF-alpha and IL-6 dose-dependently increased following nasal instillation of Al-NPs. However, polymorphonuclear leukocytes (PMNs) levels showed no significant changes in a dose dependant manner in BAL fluid. In the cytotoxicity analysis, the treatment of Al-NPs significantly and dose-dependently induced cell viability loss (20 to 30%) and damage of cell membrane (5 to 10%) in rat normal lung epithelial cells (L2). Conclusions: Our results suggest that inhaled Al-NPs in the lungs may be removed quickly by alveolar macrophages with minimal inflammatory reaction, but Al-NPs have the potential to affect lung permeability. Therefore, extensive toxicity evaluations of Al-NPs are required prior to their practical application as consumer products.