• Title/Summary/Keyword: Injection

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Young Rabbit Model for Pathophysiologic Study of Acute Lung Injury in Early Childhood (유아기 급성폐손상 병태생리 연구를 위한 어린 토끼 실험모델)

  • 권영민;최석철;박종원;김양원;이양행;황윤호;조광현
    • Journal of Chest Surgery
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    • v.36 no.8
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    • pp.545-558
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    • 2003
  • Adult respiratory distress syndrome (ARDS) is of particular interest because of its severity of the associated lung injury and its high mortality. However, the pathophysiologies of ARDS in infant and childhood groups are still not well clarified inspite of many previous investigations. To investigate the time course of pathophysiology of ARDS in infant and childhood groups, this study was designed with experimental endotoxin-induced ARDS model using young rabbits (8 week-old). Material and Method: Rabbits were divided into the control group (n=8) and the endotoxin-treated group (n=32). The endotoxin group was subdivided into 4 groups by the sampling times as 3, 6, 12 and 24 hr-groups (G- $E_{3,6,12,24,}$ each n=8). The experimental ARDS was made by a bolus injection of endotoxin (Escherichia coli serotype 055 : B5, 0.50 mg/kg) via rabbit ear vein. For evaluation of the hematologic and inflammatory markers, and superoxide dismutase (SOD) concentrations, the blood samples were taken from the heart. The bronchoalveolar lavage fluid (BALF) were obtained for analysis of the leukocytes and protein concentration. With biopsy of the lung, histopathologic changes of the lung were also evaluated. Result: In the endotoxin groups, significant leukopenia (owing to pancytopenia) occurred in 3 and 6-hr groups, which was followed by significant leukocytosis (owing to neutrophilia) in the 12 and 24-hr groups (p<0.05). Serum levels of tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-1 $\beta$ (IL-1 $\beta$) in the endotoxin groups were higher than those of control group (p<0.05). Serum levels of superoxide dismutase (SOD) of G- $E_{3}$ and G- $E_{6}$ were higher than those of control group, whereas those of G- $E_{12}$ were lower than those of control groups (p<0.05). Total leukocyte counts and protein con-centrations in BALF were significantly elevated in the endotoxin groups compared to the control group (p < 0.05). The hemorrhagic pattern of BALF showed occurred in the endotoxin groups. The endotoxin groups (in G- $E_{6}$) had severe infiltration of inflammatory cells (lymphocyte and monocyte) in the pulmonary interstitium and parenchyma, migrations of neutrophil and eosinophil into alveolar spaces and interstitial widening, which are the evidences of acute lung injury. In the endotoxin groups, there were significant positive correlations between the BALF findings and the immunologic markers (TNF-$\alpha$, IL-1$\beta$, SOD) (p<0.05). Conclusion: Severe acute lung injury occurred in all the endotoxin-treated rabbits. The pathophysiologic findings were so progressive until 6-hr by time dependant pattern, and then recovered slowly, Variable hematologic, immuno-logic, and pathologic factors were well correlated in the development and progression of endoxin-induced lung injury. The pathophysiologic responses were sensitive and rapid in young rabbit Young rabbit seemed to be a useful experimental animal model for infant and childhood groups.roups.

Biodistribution of 3-[$^{131}I$]iodo-O-methyl-L-${\alpha}$-methyltyrosine in Tumor Bearing Rats: A Comparison Study with L-3-[$^{131}I$]iodo-${\alpha}$-methyltyrosine (종양 이식 백서에서 3-[$^{131}I$iodo-O-methyl-L-${\alpha}$-methyltyrosine의 체내 동태 연구: L-3-[$^{131}I$iodo-${\alpha}$-methyltyrosine와 비교)

  • Choi, Chang-Woon;Yang, Seung-Dae;Woo, Kwang-Sun;Chung, Wee-Sup;Lim, Soo-Jung;Suh, Yong-Sup;Chun, Kwon-Soo;Ahn, Soon-Hyuk;Lee, Jong-Doo;Hong, Sung-Woon;Lim, Sang-Moo
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.3
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    • pp.290-297
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    • 1998
  • Purpose : The aim of this study was to evaluate the feasibility of 3-[$^{131}I$]iodo-O-methyl-L-${\alpha}$-methyltyrosine ([$^{131}I$]OMIMT) as an agent for tumor image. Materials and Methods : After synthesis of 4-O-methyl-L-${\alpha}$-methyltyrosine (OMAMT), OMAMT was labeled with [$^{131}I$] using Iodogen method. In vitro cellular uptake study was performed using 9 L gliosarcoma cells at various time points upto 4 hr. The biodistribution (five rats implanted with the 9 L gliosar-coma cells per group) was evaluated at 30 min, 2 hr, 24 hr after iv injection of 3.7 MBq [$^{131}I$]OMIMT or L-3-[$^{131}I$]iodo-${\alpha}$-methyltyrosine [$^{131}I$]IMT). Gamma camera images were obtained at 30 min, 2 hr and 24 hr. Results: [$^{131}I$]OMIMT uptake was 3.3 times and 2.5 times higher than [$^{131}I$]IMT uptake at 30 min and 60 min, respectively and same after 2 hr in in vitro study using 9L gliosarcoma cells. Maximum accumulation in tumor occurred at 30 min for both [$^{131}I$]OMIMT and [$^{131}I$]IMT in tumor bearing rats. The tumor uptake of [$^{131}I$]OMIMT was significantly higher than that of [$^{131}I$]IMT at early time point studied ($3.74{\pm}0.48$ vs $0.38{\pm}0.17%$ ID/g at 30 min and $2.40{\pm}0.17$ vs $0.24{\pm}0.03%$ ID/g at 2 hr, respectively, p<0.01). However, the tumor uptake of both radiolabels were not significantly different at 24 hr ($0.04{\pm}0.01$ vs $0.05{\pm}0.01%$ ID/g). Tumor was visualized as early as at 30 min in gamma camera images. Conclusion: These data suggested that [$^{131}I$]OMIMT might be a useful tumor imaging agent and has more advantage for the tumor imaging compared to [$^{131}I$]IMT

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A Refined Method for Quantification of Myocardial Blood Flow using N-13 Ammonia and Dynamic PET (N-13 암모니아와 양전자방출단층촬영 동적영상을 이용하여 심근혈류량을 정량화하는 새로운 방법 개발에 관한 연구)

  • Kim, Joon-Young;Lee, Kyung-Han;Kim, Sang-Eun;Choe, Yearn-Seong;Ju, Hee-Kyung;Kim, Yong-Jin;Kim, Byung-Tae;Choi, Yong
    • The Korean Journal of Nuclear Medicine
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    • v.31 no.1
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    • pp.73-82
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    • 1997
  • Regional myocardial blood flow (rMBF) can be noninvasively quantified using N-13 ammonia and dynamic positron emission tomography (PET). The quantitative accuracy of the rMBF values, however, is affected by the distortion of myocardial PET images caused by finite PET image resolution and cardiac motion. Although different methods have been developed to correct the distortion typically classified as partial volume effect and spillover, the methods are too complex to employ in a routine clinical environment. We have developed a refined method incorporating a geometric model of the volume representation of a region-of-interest (ROI) into the two-compartment N-13 ammonia model. In the refined model, partial volume effect and spillover are conveniently corrected by an additional parameter in the mathematical model. To examine the accuracy of this approach, studies were performed in 9 coronary artery disease patients. Dynamic transaxial images (16 frames) were acquired with a GE $Advance^{TM}$ PET scanner simultaneous with intravenous injection of 20 mCi N-13 ammonia. rMBF was examined at rest and during pharmacologically (dipyridamole) induced coronary hyperemia. Three sectorial myocardium (septum, anterior wall and lateral wall) and blood pool time-activity curves were generated using dynamic images from manually drawn ROIs. The accuracy of rMBF values estimated by the refined method was examined by comparing to the values estimated using the conventional two-compartment model without partial volume effect correction rMBF values obtained by the refined method linearly correlated with rMBF values obtained by the conventional method (108 myocardial segments, correlation coefficient (r)=0.88). Additionally, underestimated rMBF values by the conventional method due to partial volume effect were corrected by theoretically predicted amount in the refined method (slope(m)=1.57). Spillover fraction estimated by the two methods agreed well (r=1.00, m=0.98). In conclusion, accurate rMBF values can be efficiently quantified by the refined method incorporating myocardium geometric information into the two-compartment model using N-13 ammonia and PET.

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A Consideration of Apron's Shielding in Nuclear Medicine Working Environment (PET검사 작업환경에 있어서 APRON의 방어에 대한 고찰)

  • Lee, Seong-wook;Kim, Seung-hyun;Ji, Bong-geun;Lee, Dong-wook;Kim, Jeong-soo;Kim, Gyeong-mok;Jang, Young-do;Bang, Chan-seok;Baek, Jong-hoon;Lee, In-soo
    • The Korean Journal of Nuclear Medicine Technology
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    • v.18 no.1
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    • pp.110-114
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    • 2014
  • Purpose: The advancement in PET/CT test devices has decreased the test time and popularized the test, and PET/CT tests have continuously increased. However, this increases the exposure dose of radiation workers, too. This study aims to measure the radiation shielding rate of $^{18}F-FDG$ with a strong energy and the shielding effect when worker wore an apron during the PET/CT test. Also, this study compared the shielding rate with $^{99m}TC$ to minimize the exposure dose of radiation workers. Materials and Methods: This study targeted 10 patients who visited in this hospital for the PET/CT test for 8 days from May 2nd to 10th 2013, and the $^{18}F-FDG$ distribution room, patient relaxing room (stand by room after $^{18}F-FDG$ injection) and PET/CT test room were chosen as measuring spots. Then, the changes in the dose rate were measured before and after the application of the APRON. For an accurate measurement, the distance from patients or sources was fixed at 1M. Also, the same method applied to $^{99m}TC's$ Source in order to compare the reduction in the dose by the Apron. Results: 1) When there was only L-block in the $^{18}F-FDG$ distribution room, the average dose rate was $0.32{\mu}Sv$, and in the case of L-blockK+ apron, it was $0.23{\mu}Sv$. The differences in the dose and dose rate between the two cases were respectively, $0.09{\mu}Sv$ and 26%. 2) When there was no apron in the relaxing room, the average dose rate was $33.1{\mu}Sv$, and when there was an apron, it was $22.3{\mu}Sv$. The differences in the dose and dose rate between them were respectively, $10.8{\mu}Sv$ and 33%. 3) When there was no APRON in the PET/CT room, the average dose rate was $6.9{\mu}Sv$, and there was an APRON, it was $5.5{\mu}Sv$. The differences in the dose and dose rate between them were respectively, $1.4{\mu}Sv$ and 25%. 4) When there was no apron, the average dose rate of $^{99m}TC$ was $23.7{\mu}Sv$, and when there was an apron, it was $5.5{\mu}Sv$. The differences in the dose and dose rate between them were respectively, $18.2{\mu}Sv$ and 77%. Conclusion: According to the result of the experiment, $^{99m}TC$ injected into patients showed an average shielding rate of 77%, and $^{18F}FDG$ showed a relatively low shielding rate of 27%. When comparing the sources only, $^{18F}FDG$ showed a shielding rate of 17%, and $^{99m}TC$'s was 77%. Though it had a lower shielding effect than $^{99m}TC$, $^{18}F-FDG$ also had a shielding effect on the apron. Therefore, it is considered that wearing an apron appropriate for high energy like $^{18}F-FDG$ would minimize the exposure dose of radiation workers.

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A Clinical Evaluation of Splanchnic Nerve Block (내장신경차단에 관한 임상적 연구)

  • Kim, Soo-Yeoun;Oh, Hung-Kun;Yoon, Duek-Mi;Shin, Yang-Sik;Lee, Youn-Woo;Kim, Jong-Rae
    • The Korean Journal of Pain
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    • v.1 no.1
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    • pp.34-46
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    • 1988
  • Intractable pain from advanced carcinoma of the upper abdomen is difficult to manage. One method used to control pain associated with these malignancies is to block off the splanchnic nerve. In 1919 Kappis described a technique by which the splanchnic nerve of the upper abdomen could be anesthetized, using a percutaneous injection. This method has been used for the relief of upper abdominal pain due to hematoma and cancer of the pancreas, stomach, gall bladder, bile duct, and colon. During the Period from November 1968 to January 1986, this method was used in 208 cases of malignancy at Severance Hospital and clinically evaluated. Patients were retroactively grouped according to the stage of development of technique used. Twelve patients who received the treatment in the period from November 1968 to March 1977 were designate4i as group 1, 26 patients from April 1977 to April 1979 as group 2, and 170 from May 1979 to January 1986 as group 3. The results are as follows: 1) The number of patients receiving splanchnic nerve block has been increasing since 1977. 2) A total of 208 patients, including 133 males and 75 females, ranging in age from 18 to 84 and averaging 51. 3) The causes of pain were stomach cancer 90, pancreatic cancer 69, and miscellaneous cancer 49 cases respectively. 4) There were 57.7% who had surgery. and 3.7% of whom had chemotherapy before the splanchnic nerve block was done. 5) These blocks were carried out with the patient in the prone position as described by Dr. Moore. For group 2 and 3, C-arm image intensifier was used. In group 1, a 22 gauze loom long needle was inserted at the lower border of the 12th rib on each aide about 7\;cm from the midline. The average distance from the midline was $6.60{\pm}0.61\;cm$ on the left side and $6.60{\pm}0.83\;cm$ on the right side in group 2, and $5.46{\pm}0.76\;cm$ on the left side and $5.49{\pm}0.69\;cm$ on the right side in group 3. The average depth to which the needle was inserted was $8.60{\pm}0.52\;cm$ on the left side and $8.74{\pm}0.60\;cm$ on the right side in group 2, and $8.96{\pm}0.63\;cm$ on the left side and $9.18{\pm}0.57\;cm$ on the right side in group 3. 6) The points of the inserted needles were positioned in the upper quarter anteriorly, 51.8% on the left side and 54.4% n the right side of the L1 vertebra by lateral roentgenogram in group 3. The inserted needle points were located in the upper and anterolateral part, of the L1 vertebra 68.5% on the left side and 60.6won the right side, on the anteroposterior rentgenogram in group 3. The needle tip was not advanced beyond the anterior margin of the vertebral body. 7) In some case of group 3, contrast media was injected before the block was done. It shows, the spread upward along the anterior mal gin of the vertebral body. 8) The concentration and the average amount of drug used in each group was as follows: In group 1, $39.17{\pm}6.69\;ml$ of 0.5% -l% lidocaine or 0.25% bupivacaine were injected for the test block and one to three days after the test block $40.00{\pm}4.26\;ml$ of 50% alcohol was injected for the semipermanent block. In group 2, $13.75{\pm}4.88\;ml$ of 1% lidocaine were used as the test block and followed by $46.17{\pm}4.37\;ml$ of 50% alcohol was injected as the semipermanent block. In group 3, $15.63{\pm}1.19\;ml$ of 1% lidocaine for test block followed by $15.62{\pm}1.20\;ml$ of pure alcohol and $16.05{\pm}2.58\;ml$ of 50% alcohol for semipermanent block were injected. 9) The result of the test block was satisfactory in all cases. However the semipermanent block was 83.3 percent of the patients in group 1 who received relief from pain for at least 2 weeks after the block, 73.1% in group 2, and 91.8% in group 3. In these unsuccessful cases, 2 cases in group 1 were controlled by narcotics but 7 cases in group 2 and 14 cases in group 3 received the same splanchnic nerve block 1 or 2 times again within 2 weeks. But, in some cases it was 3 to i months before the 2nd block and in 1 cases even 7 years. 10) The most common complications of splanchnic nerve block were hypotensino(25.5%) occasional flushing of the face, nausea, vomiting, and chest discomfort. 11) For the patients in group 3, the supplemental block most commonly used was a continuous epidural block; it was used as a diagnostic block and to afford relief from pain before the splanchnic nerve block was done. 12) The interval between the receiving of the alcohol block and discharge was from 5 to 8 days in 61 cases(31.1%) and from 1 to 2 days in 48 cases(24.5%). From the above results, it can be concluded that the splanchnic nerve block done in the prone position with pure and 50% alcohol immediately after an effective test block with 1% lidocaine under C-arm fluoroscopic control is satisfactory and reliable. How to minimize the repeat block is still a problem to be solved.

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The Protective Effects of Ethanol Extract of Wild Simulated Ginseng on Carbon Tetrachloride Induced Acute Hepatic Injury in Mouse (사염화탄소 유발 급성 간독성 생쥐모델에서 산양삼 에탄올 추출물의 간 보호 효과)

  • Lee, Soo-Min;Park, Sun-Young;Jang, Gi-Seuk;Ly, Sun-Yung
    • Journal of Nutrition and Health
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    • v.41 no.8
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    • pp.701-710
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    • 2008
  • The wild simulated ginseng (WSG) has been effectively used in folk medicine as a remedy against hepatic disease, hypertension and arthritic disease. However, there is still lack of scientific proof about its antioxidant capability. The present study has been conducted to evaluate the protective role of the WSG ethanol extract in the CCl4-induced oxidative stress and resultant hepatic disfunction in ICR mice. The electron donating abilities and IC50 of WSG etnanol extract were 76.86 ${\pm}$ 1.06% and 33.3 ${\mu}g$/mL (that of ascobic acid was 16.5 ${\mu}g$/mL), respectively. Total antioxidant status of WSG extract was 2.13 ${\pm}$ 0.06 mmoL/mg, while the values of ascorbic acid and BHT were 3.63 ${\pm}$ 0.06 and 3.12 ${\pm}$ 0.02, respectively. ICR mice (aged 3weeks) were fed for 4 weeks on AIN-93M diet and had free access to food and water. The animals were divided into three groups: normal group (intraperitoneally (i.p) injected with PBS at 100 ${\mu}L$/mouse), group C; CCl4-induced and without any treatment. (i.p injected only PBS, 100 ${\mu}L$ /mice), group G; CCl4-induced and treated with WSG (i.p injected with 5 mg WSG extract per mouse, suspended in 100 ${\mu}L$ phosphate buffer). After the i.p. injection of WSG or PBS (5 times for 7weeks), all mice were administered CCl4 in olive oil at the last day of the experiment, except for normal group. The normal group was administered only olive oil. Determination of plasma triglyceride, total cholersterol, fasting glucose and GPT activity was performed using automatic blood analyzer. To evaluate the protective effect against the oxidative stress, DNA fragmentation and TBARS were determined in blood leucocytes and RBC and hepatocyte, respectively. Body and organs weights and food intake did not show significant differences among the groups. Blood total cholesterol of group G was similar to that of normal group, which was the lowest in group C. The fasting blood glucose level was the highest in normal group (205.20 ${\pm}$ 135.24), which were decreased in group C (134.2 ${\pm}$ 79.31) and group G (126.48 ${\pm}$ 77.05). TBARS values in a red blood cell and hepatic tisuue homogenate were lower in group G comparing to the group C. DNA% in tail, tail length (TL) and tail moment (TM) of blood leucoocytes showed the highest values in group C (20.11 ${\pm}$ 2.47, 17.36 ${\pm}$ 2.58, 94.11 ${\pm}$ 12.29) and they were significantly diminished in group G (9.63 ${\pm}$ 1.19, 7.04 ${\pm}$ 1.50, 38.64 ${\pm}$ 7.60). In conclusion, wild simulated ginseng might be a protective agent against the oxidative stress.

The Ability of Anti-tumor Necrosis Factor Alpha(TNF-${\alpha}$) Antibodies Produced in Sheep Colostrums

  • Yun, Sung-Seob
    • 한국유가공학회:학술대회논문집
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    • 2007.09a
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    • pp.49-58
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    • 2007
  • Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.

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The Role of Protein Kinase C in Acute Lung Injury Induced by Endotoxin (내독소에 의한 급성폐손상에서 Protein Kinase C의 역할)

  • Kim, Yong-Hoon;Moon, Seung-Hyug;Kee, Sin-Young;Ju, Jae-Hak;Park, Tae-Eung;Im, Keon-Il;Cheong, Seung-Whan;Kim, Hyeon-Tae;Park, Choon-Sik;Jin, Byung-Won
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.2
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    • pp.349-359
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    • 1997
  • Background : The signal pathways and their precise roles for acute respiratory distress syndrome caused by endotoxin (ETX) has not been established. Since there has been several in vitro experiments suggesting that activation of protein kinase C (PKC) pathway may be responsible for endotoxin-induced inflammatory reaction, we performed in vivo experiments in the rats with the hypothesis that PKC-inhibition can effectively prevent endotoxin-induced acute lung injury. Methods : We studied the role of PKC in ETX-induced ALI using PKC inhibitor (staurosporine, STP) in the rat Specific pathogen free male Sprague-Dawley weighted from 165 to 270g were used for the study. Animals were divided into the normal control (NC)-, vehicle control (VC)-, ETX-, PMA (phorbolmyristateacetate)-, STP+PMA-, and STP+ETX-group. PMA (50mg/kg) or ETX (7mg/kg) was instilled through polyethylen catheter after aseptic tracheostomy with and without STP (0.2mg/kg)-pretreatment STP was injected via tail vein 30min before intratracheal injection (IT) of PMA or ETX. Bronchoalveolar lavage (BAL) was done 3-or 6-hrs after IT of PMA or ETX respectively, to measure protein concentration, total and differential cell counts. Results : The results were as follows. The protein concentrations in BALF in the PMA- and ETX-group were very higher than that of VC-group (p<0.001). When animals were pretreated with STP, the %reduction of the protein concentration in BALF was $64.8{\pm}8.5$ and $30.4{\pm}2.5%$ in the STP+PMA- and STP+ETX-group, respectively (p = 0.028). There was no difference in the total cell counts between the PMA-and VC-group (p = 0.26). However the ETX-group showed markedly increased total cell counts as compared to the VC- (p = 0.003) and PMA-group (p = 0.0027), respectively. The total cell counts in BALF were not changed after pretreatment with STP compared to the PMA- (p = 0.22) and ETX-group (p = 0.46). The percentage of PMN, but not alveolar macrophage, was significantly elevated in the PMA-, and ETX-group. Especially in the ETX-group, the percentage of PMN was 17 times higher than that of PMA (p < 0.001). The differential cell counts was not different between the PMA and STP+PMA On the contrary the STP+ETX-group showed decreased percentage of PMN (p = 0.016). There was no significant relationship between the protein concentration and the total or differential cell counts in each group. Conclusion : Pretreatment with PKC-inhibitor (staurosporine) partially but significantly inhibited ETX-induced ALI.

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Effects of FK224, a $NK_1$ and $NK_2$ Receptor Antagonist, on Plasma Extravasation of Neurogenic Inflammation in Rat Airways (미주 신경의 전기적 자극으로 유발된 백서의 기도내 혈장 유출에 대한 FK224의 효과)

  • Shim, Jae-Jeong;Lee, Sang-Yeub;Lee, Sang-Hwa;Park, Sang-Myun;Seo, Jeong-Kyung;Cho, Jae-Yun;In, Kwang-Ho;Yoo, Se-Hwa;Kang, Kyung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.5
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    • pp.744-751
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    • 1995
  • Background: Asthma is an inflammatory disease because there are many inflammatory changes in the asthmatic airways. Axon reflex mechanisms may be involved in the pathogenesis of asthma. Sensory neuropeptides are involved in this inflammation, which is defined as neurogenic inflammation. Substance p, neurokinin A, and neurokinin B may be main neuropeptides of neurogenic inflammation in airways. These tachykinins act on neurokinin receptors. Three types of neurokinin receptors, such as $NK_1$, $NK_2$, and $NK_3$, are currently recognized, at which substance p, neurokinin A, and neurokinin B may be the most relevant natural agonist of neurogenic inflammation in airways. The receptor subtypes present in several tissues have been characterized on the basis of differential sensitivity to substance p, neurokinin A, and neurokinin B. Plasma extravasation and vasodilation are induced by substance p more potently than by neurokinin A, indicating NK1 receptors on endothelial cells mediate the response. But airway contraction is induced by neurokinin A more potently than by substance P, indicating the $NK_2$ receptors in airway smooth muscles. These receptors are used to evaluate the pathogenesis of brochial asthma. FK224 was identified from the fermentation products of Streptomyces violaceoniger. FK224 is a dual antagonist of both $NK_1$ and $NK_2$ receptors. Purpose: For a study of pathogenesis of bronchial asthma, the effect of FK224 on plasma extravasation induced by vagal NANC electrical stimulation was evaluated in rat airway. Method: Male Sprague-Dawley rats weighing 180~450gm were anesthetized by i.p. injection of urethane. Plasma extravasation was induced by electrical stimulation of cervical vagus NANC nerves with 5Hz, 1mA, and 5V for 2 minutes(NANC2 group) and for sham operation without nerve stimulation(control group). To evaluate the effect of FK224 on plasma extravasation in neurogenic inflammation, FK224(1mg/kg, Fujisawa Pharmaceutical Co., dissolved in dimethylsulphoxide; DMSO, Sigma Co.) was injected 1 min before nerve stimulation(FK224 group). To assess plasma exudation, Evans blue dye(20mg/kg, dissolved in saline) was used as a plasma marker and was injected before nerve stimulation. After removal of intravascular dye, the evans blue dye in the tissue was extracted in formamide($37^{\circ}C$, 24h) and quantified spectrophotometrically by measuring dye absorbance at 629nm wavelength. Tissue dye content was expressed as ng of dye per mg of wet weight tissue. The amount of plasma extravasation was measured on the part of airways in each groups. Results: 1) Vagus nerve(NANC) stimulation significantly increased plasma leakage in trachea, main bronchus, and peripheral bronchus compared with control group, $14.1{\pm}1.6$ to $49.7{\pm}2.5$, $17.5{\pm}2.0$ to $38.7{\pm}2.8$, and $12.7{\pm}2.2$ to $19.1{\pm}1.6ng$ of dye per mg of tissue(mean ${\pm}$ SE), respectively(p<0.05). But there was not significantly changed in lung parenchyma(p>0.05) 2) FK224 had significant inhibitory effect upon vagal nerve stimulation-induced airway plasma leakage in any airway tissues of rat,such as trachea, main bronchus, and peripheral bronchus compared with vagus nerve stimulation group, 49%, 58%, and 70%, respectively(p<0.05). Inhibitory effect of FK224 on airway plasma leakage in neurogenic inflammation was revealed the more significant in peripheral bronchus, but no significant in lung parenchyma. Conclusion: These results suggest that FK224 is a selective NK receptor antagonist which effectively inhibits airway plasma leakage induced by the endogenous neurotransmitters relased by neurogenic inflammation in rat airway. Tachykinin receptor antagonists may be useful in the treatment of brochial asthma.

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Development of Quantification Methods for the Myocardial Blood Flow Using Ensemble Independent Component Analysis for Dynamic $H_2^{15}O$ PET (동적 $H_2^{15}O$ PET에서 앙상블 독립성분분석법을 이용한 심근 혈류 정량화 방법 개발)

  • Lee, Byeong-Il;Lee, Jae-Sung;Lee, Dong-Soo;Kang, Won-Jun;Lee, Jong-Jin;Kim, Soo-Jin;Choi, Seung-Jin;Chung, June-Key;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.6
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    • pp.486-491
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    • 2004
  • Purpose: factor analysis and independent component analysis (ICA) has been used for handling dynamic image sequences. Theoretical advantages of a newly suggested ICA method, ensemble ICA, leaded us to consider applying this method to the analysis of dynamic myocardial $H_2^{15}O$ PET data. In this study, we quantified patients' blood flow using the ensemble ICA method. Materials and Methods: Twenty subjects underwent $H_2^{15}O$ PET scans using ECAT EXACT 47 scanner and myocardial perfusion SPECT using Vertex scanner. After transmission scanning, dynamic emission scans were initiated simultaneously with the injection of $555{\sim}740$ MBq $H_2^{15}O$. Hidden independent components can be extracted from the observed mixed data (PET image) by means of ICA algorithms. Ensemble learning is a variational Bayesian method that provides an analytical approximation to the parameter posterior using a tractable distribution. Variational approximation forms a lower bound on the ensemble likelihood and the maximization of the lower bound is achieved through minimizing the Kullback-Leibler divergence between the true posterior and the variational posterior. In this study, posterior pdf was approximated by a rectified Gaussian distribution to incorporate non-negativity constraint, which is suitable to dynamic images in nuclear medicine. Blood flow was measured in 9 regions - apex, four areas in mid wall, and four areas in base wall. Myocardial perfusion SPECT score and angiography results were compared with the regional blood flow. Results: Major cardiac components were separated successfully by the ensemble ICA method and blood flow could be estimated in 15 among 20 patients. Mean myocardial blood flow was $1.2{\pm}0.40$ ml/min/g in rest, $1.85{\pm}1.12$ ml/min/g in stress state. Blood flow values obtained by an operator in two different occasion were highly correlated (r=0.99). In myocardium component image, the image contrast between left ventricle and myocardium was 1:2.7 in average. Perfusion reserve was significantly different between the regions with and without stenosis detected by the coronary angiography (P<0.01). In 66 segment with stenosis confirmed by angiography, the segments with reversible perfusion decrease in perfusion SPECT showed lower perfusion reserve values in $H_2^{15}O$ PET. Conclusions: Myocardial blood flow could be estimated using an ICA method with ensemble learning. We suggest that the ensemble ICA incorporating non-negative constraint is a feasible method to handle dynamic image sequence obtained by the nuclear medicine techniques.