• Title/Summary/Keyword: $SO_4^{2-}$ uptake

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Development of High Intensity Focused Ultrasound (HIFU) Mediated AuNP-liposomal Nanomedicine and Evaluation with PET Imaging

  • Ji Yoon Kim;Un Chul Shin;Ji Yong Park;Ran Ji Yoo;Soeku Bae;Tae Hyeon Choi;Kyuwan Kim;Young Chan Ann;Jin Sil Kim;Yu Jin Shin;Hokyu Lee;Yong Jin Lee;Kyo Chul Lee;Suhng Wook Kim;Yun-Sang Lee
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.9 no.1
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    • pp.9-16
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    • 2023
  • Liposomes as drug delivery system have proved useful carrier for various disease, including cancer. In addition, perfluorocarbon cored microbubbles are utilized in conjunction with high-intensity focused-ultrasound (HIFU) to enable simultaneous diagnosis and treatment. However, microbubbles generally exhibit lower drug loading efficiency, so the need for the development of a novel liposome-based drug delivery material that can efficiently load and deliver drugs to targeted areas via HIFU. This study aims to develop a liposome-based drug delivery material by introducing a substance that can burst liposomes using ultrasound energy and confirm the ability to target tumors using PET imaging. Liposomes (Lipo-DOX, Lipo-DOX-Au, Lipo-DOX-Au-RGD) were synthesized with gold nanoparticles using an avidin-biotin bond, and doxorubicin was mounted inside by pH gradient method. The size distribution was measured by DLS, and encapsulation efficiency of doxorubicin was analyzed by UV-vis spectrometer. The target specificity and cytotoxicity of liposomes were assessed in vitro by glioblastoma U87mg cells to HIFU treatment and analyzed using CCK-8 assay, and fluorescence microscopy at 6-hour intervals for up to 24 hours. For the in vivo study, U87mg model mouse were injected intravenously with 1.48 MBq of 64Cu-labeled Lipo-DOX-Au and Lipo-DOX-Au-RGD, and PET images were taken at 0, 2, 4, 8, and 24 hours. As a result, the size of liposomes was 108.3 ± 5.0 nm at Lipo-DOX-Au and 94.1 ± 12.2 nm at Lipo-DOX-Au-RGD, and it was observed that doxorubicin was mounted inside the liposome up to 52%. After 6 hours of HIFU treatment, the viability of U87mg cells treated with Lipo-DOX-Au decreased by around 20% compared to Lipo-DOX, and Lipo-DOX-Au-RGD had a higher uptake rate than Lipo-DOX. In vivo study using PET images, it was confirmed that 64Cu-Lipo-DOX-Au-RGD was taken up into the tumor immediately after injection and maintained for up to 4 hours. In this study, drugs released from liposomes-gold nanoparticles via ultrasound and RGD targeting were confirmed by non-invasive imaging. In cell-level experiments, HIFU treatment of gold nanoparticle-coupled liposomes significantly decreased tumor survival, while RGD-liposomes exhibited high tumor targeting and rapid release in vivo imaging. It is expected that the combination of these models with ultrasound is served as an effective drug delivery material with therapeutic outcomes.

Diagnostic Efficacy of FDG-PET Imaging in Solitary Pulmonary Nodule (고립성폐결절의 진단시 FDG-PET의 임상적 유용성에 관한 연구)

  • Cheon, Eun Mee;Kim, Byung-Tae;Kwon, O. Jung;Kim, Hojoong;Chung, Man Pyo;Rhee, Chong H.;Han, Yong Chol;Lee, Kyung Soo;Shim, Young Mog;Kim, Jhingook;Han, Jungho
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.6
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    • pp.882-893
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    • 1996
  • Background : Over one-third of solitary pulmonary nodules are malignant, but most malignant SPNs are in the early stages at diagnosis and can be cured by surgical removal. Therefore, early diagnosis of malignant SPN is essential for the lifesaving of the patient. The incidence of pulmonary tuberculosis in Korea is somewhat higher than those of other countries and a large number of SPNs are found to be tuberculoma. Most primary physicians tend to regard newly detected solitary pulmonary nodule as tuberculoma with only noninvasive imaging such as CT and they prefer clinical observation if the findings suggest benignancy without further invasive procedures. Many kinds of noninvasive procedures for confirmatory diagnosis have been introduced to differentiate malignant SPNs from benign ones, but none of them has been satisfactory. FOG-PET is a unique tool for imaging and quantifying the status of glucose metabolism. On the basis that glucose metabolism is increased in the malignant transfomled cells compared with normal cells, FDG-PET is considered to be the satisfactory noninvasive procedure which can differentiate malignant SPNs from benign SPNs. So we performed FOG-PET in patients with solitary pulmonary nodule and evaluated the diagnostic accuracy in the diagnosis of malignant SPNs. Method : 34 patients with a solitary pulmonary nodule less than 6 cm of irs diameter who visited Samsung Medical Center from Semptember, 1994 to Semptember, 1995 were evaluated prospectively. Simple chest roentgenography, chest computer tomography, FOG-PET scan were performed for all patients. The results of FOG-PET were evaluated comparing with the results of final diagnosis confirmed by sputum study, PCNA, fiberoptic bronchoscopy, or thoracotomy. Results : (I) There was no significant difference in nodule size between malignant (3.1 1.5cm) and benign nodule(2.81.0cm)(p>0.05). (2) Peal SUV(standardized uptake value) of malignant nodules (6.93.7) was significantly higher than peak SUV of benign nodules(2.71.7) and time-activity curves showed continuous increase in malignant nodules. (3) Three false negative cases were found among eighteen malignant nodule by the FDG-PET imaging study and all three cases were nonmucinous bronchioloalveolar carcinoma less than 2 em diameter. (4) FOG-PET imaging resulted in 83% sensitivity, 100% specificity, 100% positive predictive value and 84% negative predictive value. Conclusion: FOG-PET imaging is a new noninvasive diagnostic method of solitary pulmonary nodule thai has a high accuracy of differential diagnosis between malignant and benign nodule. FDG-PET imaging could be used for the differential diagnosis of SPN which is not properly diagnosed with conventional methods before thoracotomy. Considering the high accuracy of FDG-PET imaging, this procedure may play an important role in making the dicision to perform thoracotomy in diffcult cases.

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A Comparative Study on the Chemical Methods for the Determination of Available Phosphorus in Korean Soils (한국토양(韓國土壤)의 유효인산량(有效燐酸量) 검정(檢定)을 위한 화학적(化學的) 방법(方法)에 대한 연구(硏究))

  • Lim, Sun-Uk;Chung, Jong-Bae;Sa, Tong-Min
    • Applied Biological Chemistry
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    • v.29 no.1
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    • pp.62-72
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    • 1986
  • At present, the definition and chemical analysis method of available soil phosphorus for plants have not been standardized because of the complexity of crop and soil characteristics in Korea and many analysis methods have been suggested with different extraction conditions. Suitable analytical method of available soil P should be established by the trial of various methods based on crop nutrition and soil conditions. To establish the most suitable analysis method of available soiIP, a pot experiment with young maize was conducted over 44 different upland soils collected over the land of Korea. The amount of uptaken P by the plant was determined by ten different chemical methods for the available soil P. The results obtained were as follows: 1. Total phosphorus content in the sample soils ranged ranged $533{\sim}4917\;ppm$, and showed significant positive correlation with the content of organic matter. 2. The P content was relatively low in the acid sulfate soil and very high in the volcanic ash soil although both types of soil contained high level of orgic matter. 3. The amount of extractable P determined by ten different methods were varied more or less, and the ratios of the extractable P to the total soil P were in the range of $1{\sim}48%$. 4. The relative values to the amount of extractable soil P by different methods were in the order of $H_2O(5\;min.)\;1.0\;<\;H_2O(60min.)\;2.27\;<\;NH_4HCO_3\;5.57\;<\;NaHCO_3\;7.42\;<\;Double\;lactate\;9.71\;<\;Bray\;No.1\;12.53\;<\;Lancaster\;17.63\;<\;Nelson\;25.96\;<\;AcOH\;27.6\;<\;CAL-method\;50.27$ 5. The amount of extractable P determined by all of applied methods was very low in acid sulfate soil, volcanic ash soil and coarse textured soil. 6. Soil pH and total soil P generally showed significant positive correlation with the chemically extracted P, and soil organic matter was negatively correlated with the determined by Nelson-and CAL-method. Olsen method which showed significant correlation with exchangeable calcium seemed to be recommendable for calcareous soils. 7. Total amount of uptaken P by Young maize through continuos twice cropping was 4.05% of total soil P in average, and the uptake in the second cropping was twice as much as that of the first cropping. 8. Three determination methods, i.e. Soltanpour-, Double lactate and Bray No. 1-method seemed to be more suitable than Lancaster method which is widely practiced at present in Korea. However, further study should be carried out with other crops and soils to most adequate chemical method for determination of available soil P.

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Experimental Studies on Cardiac Catecholamine Content (Catecholamines에 관(關)하여 -제삼편(第三編) 심장(心臟) Catecholamines에 관(關)한 실험적(實驗的) 연구(硏究)-)

  • Lee, Woo-Choo
    • The Korean Journal of Pharmacology
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    • v.9 no.1
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    • pp.1-21
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    • 1973
  • During the last decade extensive studios on catecholamines have evolved new knowledge in the physiology and biochemistry of adrenergic mechanism. Cardiac muscle, receiving adrenergic fibres from the stellate, cervical and thoracic ganglia, has been repeatedly shown to have a specific capacity to uptake and to store catecholamines. The catecholamine stores in cardiac muscle have also been shown to be important sites for the action of numerous drugs. Under normal condition, a certain level of catecholamines is maintained in the stores and serves as the basis for studying the changes in the catecholamine content of the heart. Because myocardial catecholamines play such important role in the patho-physiology of the heart, it would be interesting to compare the normal level of myocardial catecholamines among various species of animals. An occasional study has dealt with myocardial catecholamines of several species add ages of animals but these have been insufficiently comprehensive to afford a basis for an understanding of the importance of these amines as related to species and ages. The present investigation was undertaken to determine whether or not there is any significance of myocardial catecholamines in the course of the evolution and development of animals. Seasonal changes, sex difference and regional and subcellular distribution of myocardial catecholamines were also examined. The concentration of cardiac catecholamines was determined by the spectrophotofluorometric procedure described by Shore and Olin. The results obtained were summarized as follows: 1. As animals phylogenetically progressed larger amounts of catecholamines were resent in their hearts. A negligibly small amount of catecholamine was present in the hearts of the clam, a non-vertebrate. Among the vertebrates, cold-blooded animals (snake, turtle, frog, eel and fish) had less myocardial catecholamines than warm-blooded animals, of which aves (fowl and duck) had less than mammalia (cat, dog, rabbit, rat, cow and pig). The ratio of norepinephrine to epinephrine also was greater as the animals progress phylogenetically. 2. Examination of the regional distribution of cardiac catecholamines in warm-blooded animals showed that the content of the auricle was generally higher than that of the septum and considerably than that of the ventricle, but the differences of contents among these regions were not so marked. 3. In the embryonic chick, cardiac catecholamines were firstly detected on the 4th day of incubation, the time before the cardiac innervation of sympathetic nerves. The concentrations of these catecholamines increased but not markedly on the 6th day of incubation, soon after the innervation of sympathetic nerves to the heart. The level of the cardiac catecholamines fluctuated throughout the remainder of embryonic development. 4. In newborn rat hearts, a considerable amount of catecholamines was present. With the development of the rats, the concentrations of myocardial catecholamines increased. The ratio of epinephrine and norepinephrine fluctuated within the range of 40 to 60 pervent. However, as development progressed, the percentage of norepinephrine continued to rise, attaining the adult value of $80{\sim}90%$ after $45{\sim}60$ days. In contrast, the total amount of epinephrine remained fairly constant throughout the animal's development. 5. No significant sexual differences were observed in the concentration of myocardial catecholamines in the developing rat. 6. The catecholamines in the rabbit hearts increased during the summer season (from May to August) and maintained a fairly constant level in the other seasons of the year. 7. The subcellular distribution of cardiac catecholamines was examined by differential centrifugation of homogenates of cardiac muscles in rabbits, cats and rats. The catecholamines were found to be present approximately 20% in particles of mitochondrial fraction, 45% in particles of microsomal fraction and 35% in soluble supernatant fraction. The particle containing catecholamines in cardiac muscle appears to be two different sizes.

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Effect of Mixed Liquid Fertilization on Growth Responses of Cherry Tomatoes and Soil Chemical Properties (생초미생물혼합액비의 시용이 방울토마토의 생육반응과 토양화학성에 미치는 영향)

  • Park, Ji-Suk;Lee, Min-Jin;Lee, Seo-Youn;Kim, Jong-Sung;Lee, Tae-Kyu;Ro, Hee-Myong;Kim, Sang-Jun;Jeon, Seung-Woo;Seo, Sang-Gug;Kim, Kil-Yong;Lee, Geon-Hyoung;Jeong, Byung-Gon
    • Horticultural Science & Technology
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    • v.33 no.2
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    • pp.268-275
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    • 2015
  • We evaluated the effect of mixed liquid fertilizer (MLF) on growth responses of plants and soil chemical properties. To do so, a pot experiment with cherry tomatoes (Lycopersicon esculentum var. cerasiforme) using loam soil was conducted for 81 days in a temperature-controlled glasshouse, and four N fertilization treatments were laid out in a completely randomized design with three replicates: control (C), chemical fertilizer treatment (CF), and two rates (MLF-0.5 and MLF-1.0) of MLF treatment. Soils were periodically sampled and analyzed for pH, EC, total N, inorganic N and total C, and growth characteristics of cherry tomatoes were measured. During the experimental periods, the pH of MLF soils was higher than that of CF soils. Soil total-N content increased right after CF-application and ultimately decreased to the level of the control (C) soil, while MLF-application slightly increased the level of soil total-N and this level remained unchanged throughout the experiment. The levels of soil inorganic N content increased after application of CF or MLF, but the initial increase disappeared in 56 days after transplanting (DAT). The dry weight of shoots and roots increased in CF or MLF plants, while the number of fruit increased only in MLF plants. Whereas soluble solid contents were higher in MLF plants than in the other (C and CF) plants, the titratable acidity was not different among treatments. However, no consistent effect of N treatments on major elements of the organs of cherry tomatoes was found. The amounts of N taken up by plants were 0.91 g for CF, 0.61 g for MLF-1.0, 0.43 g for MLF-0.5, and 0.25 g for control treatments, resulting in greater N efficiency for CF than for MLF.

Usefulness of Stomach Extension after Drinking Orange Juice in PET/CT Whole Body Scan (PET/CT 전신 영상에서 오렌지 주스(Orange Juice)를 이용한 위장 확장 영상의 유용성)

  • Cho, Seok-Won;Chung, Seok;Oh, Shin-Hyun;Park, Hoon-Hee;Kim, Jae-Sam;Lee, Chang-Ho
    • The Korean Journal of Nuclear Medicine Technology
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    • v.13 no.1
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    • pp.86-92
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    • 2009
  • Purpose: The PET/CT has a clear distinction on the lesion of the functional image by adding anatomical information. It also could reduce the examination time using CT data as the attenuation-correction. When the stomach was contracted from a fast, it could bring a misinterpretation of the cancer of the lesion with a presence of physiological $^{18}F$-FDG uptake in stomach and it occasionally would bring an additional scan to confirm. To complement this shortcoming, the method that the patients had water before the examination to extend the stomach had been attempted. However, a short excretion time of the stomach did not give sufficiently extended image of the stomach. Then the patients had additional water and had the examination again. Therefore, the noticed fact is that the stomach excretion time depends on calories, protein content, and the level of carbohydrate. In this study, we use an orange juice to evaluate the extension of the stomach and usefulness of it. Materials and Methods: PET/CT scan were obtained on total 150 of patient from February 2008 to October2008, There were 3 groups in this study and each group had 50 patients. First group drank nothing, Second group drank water and third group drank orange juice. The patients (man 25, female 25) not drinking are the age of 30~71 years old (average: 54), the patients (man: 25, female: 25) drinking water (400 cc) are the age of 28~71 years old (average: 54) and the patients (man: 25, female: 25) drinking orange juice (400 cc) are the age of 32~74 years old (average: 56). The patients were fasted in 6-8 hours before the test, the patients were not diabetic. $^{18}F$-FDG 370~555 MBq were injected intravenously. The patients were in stable position for 1 hour, than the image was obtained. The patients drank water and other patients drank orange juice before Whole body scan. The image scan started from mid-femur to skull base. The emission scan acquired for three minutes per bed and the images were reconstructed. Stomach extension analysis is measured from vertical and horizontal length. Results: Stomach Extension was described as the vertical length of the Non Drink Group was $1.20{\pm}0.50\;cm$, horizontal length was $1.4{\pm}0.53\;cm$, the vertical length of the Water Drink Group was $1.67{\pm}0.63\;cm$, horizontal length was $1.65{\pm}0.77\;cm$, the vertical length of Orange juice Drink Group was $3.48{\pm}0.77\;cm$, horizontal length was $3.66{\pm}0.77\;cm$ in coronal image. Stomach Extension was described the vertical length of the Non Drink Group was $2.03{\pm}0.62\;cm$, horizontal length was $1.69{\pm}0.68\;cm$, the vertical length of Water Drink Group was $5.34{\pm}1.62\;cm$, horizontal length was $2.45{\pm}0.72\;cm$, the vertical length of Orange juice Drink Group was $7.74{\pm}1.62\;cm$, horizontal length was $3.57{\pm}0.77\;cm$ in transverse image. The Stomach Extension has specific differences (p<0.001). The SUVs shows the Non Drink Group were measured as Liver $2.52{\pm}0.42$, Lung $0.51{\pm}0.14$, the Water Drink Group were measured as Liver $2.47{\pm}0.38$, Lung $0.50{\pm}0.14$, Orange juice Drink Group were measured as Liver $2.47{\pm}0.38$, Lung $0.50{\pm}0.14$. The SUVs did not have specific differences (p>0.759). Conclusions: There was not a large difference of SUV in three groups. When the patients drank Orange juice and water, the range extension of stomach was higher than without drinking nothing and it was possible to acquire fully extended images. Therefore, it will be possible that unnecessary additional stomach scans will be reduced by drinking orange juice before the examination so that the patients' claim from uncomfortable and long period of fast will be minimized.

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