• Journal of Oral Medicine and Pain
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• v.36 no.1
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• pp.11-20
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• 2011

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent. And it is known that antitmor activity of VPA is associated with its targeted at histone deacetylases. 17AAG, Inhibition of HSP90 leads to the proteasome degradation of the HSP90 client proteins, such as Akt, Raf/Ras, Erk, VEGF, cyclin D and p53, and causes potent antitumor activity. It is reported that 17AAG-induced HSP90 inhibition results in prevention of cell proliferation and induction of apoptosis in several types of cancer. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and the HSP90 inhibitor, 17AAG on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and 17AAG showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-3, caspase-7 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or 0.5 ${\mu}M$ 17AAG for 48 h did not induce apoptosis, the co-treatment with them induced prominently apoptosis. Therefore our data in this study provide the possibility that combination therapy with VPA and 17AAG could be considered as a novel therapeutic strategy for human osteosarcoma.

• Journal of Nutrition and Health
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• v.1 no.2
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• pp.107-115
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• 1968

Number of aspects, not only nutritional but social as well as political involved in human starvation pose nowadays global problems. In order to help establish the minimum nutritional requirements in the daily life of a man and to free people as well from either undernourishment, malnutrition or even starvation many workers have devoted themselves so far on the research programs to know what and how number of metabolic events take place in animals in vivo. It is the purpose of the present paper to examine in effect to what extent both of the protein and nucleic acids (DNA & RNA) together with an enzyme, guanine deaminase, which converts guanine into xanthine and in turn ends up to uric acid as an end product, undergo changes, quantitatively during acute starvation, using the mouse as an experimental animal. The mouse was strictly inhibited from taking foods except drinking water ad libitum and was sacriflced 24, 48, and 72 hours following starvation thus acutely induced. The animals consisted of two experimental groups, one control and another starvation groups, each being consisted of 6-24 mice of whose body weights ranged in the vicinity of 10 g. The animals were sacriflced by a blow on the head, followed by immediate excision of their livers into ice-cold distilled water, washing adherent blood and other contaminant tissues. The liver was minced foramin, by an all-glass homogenizer immersing it in an ice-bath, followed by subsequent fractionatin of the homogenate (10% W/V in 0.25M sucrose solution made up with 0.05M phosphate buffer of pH 7.4). For the liver protein and guanine deaminase assay, the 10% homogenate was centrifuged at 600 x g for 10 minutes to eliminate the nuclear fraction; and for the estimation of DNA and RNA, the homogenate was prepared by the addition of 10% trichloroacetic acid in order to free the homogenate from the acid-soluble fraction, the remaining residue being delipidate by the addition of alcohol and dried in vacuo for later KOH (IN) hydrolysis. The changes in body and liver wegihts during acute starvation were checked gravimetrically. Protein contents in the liver were monitored by the method of Lowry et al; and guanine deaminase activities were followed by the assay of liberated ammonia from the substrate utilizing the Caraway's colorimetry. The extraction of both DNA and RNA was performed by the Schmidt-Thannhauser's method, which was followed by Marmur's method of purification for DNA and by Chargaff's method of purification for RNA. The determinations of both DNA and RNA were carried out by the diphenylamine reaction for the former and by the orcinol reaction for the latter. The following resume was the results of the present work. 1. It was observed that the body as well as liver weights fall abruptly during starvation, and that the loss of body weight showed no statistical correlation with the decreases in the content of liver protein. 2. The content of liver protein and activity of liver guanine deaminase activity as well decline dramatically, and the specific activities of the enzyme (activity/protein), however, decreased gradually as starvation proceeded. 3. Both of the nucleic acids, DNA and RNA, showed decrements in the liver of mouse during acute starvation; the latter, however, being more striking in the decline as compared to the former. 4. The decreases in the liver protein content as resulted from the acute starvation had no statistically significant correlation with the decrements of DNA in the same tissue, but had regressed with a significant statistical correlation with the fall of RNA in the tissue. 5. The decrease in the activity of guanine deaminase in the liver of mouse during acute starvation was functionally more proportional to the decrease in RNA than DNA, and moreover correlated with the changes in the content of the liver protein. 6. The possible mechanisms involved during in this acute starvation as bring the decreases in the contents of DNA, protein, and guanine deaminase were discussed briefly.

• Progress in Medical Physics
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• v.21 no.2
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• pp.174-182
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• 2010

In this study, we evaluated feasibility of applying MTV (Metabolic Target Volume) to respiratory gated radiotherapy for more accurate treatment using various SUV (Standard Uptake Value) from PET images. We compared VOI (Volume of Interest) images from 50%, 30% and 5% SUV (standard uptake volume) from PET scan of an artificial target with GTV (Gross Tumor Volume) images defined by percentage of respiratory phase from 4D-CT scan for respiratory gated radiotherapy. It is found that the difference of VOI of 30% SUV is reduced noticeably comparing with that of 50% SUV in longitudinal direction with respect to total GTV of 4D-CT image. Difference of VOI of 30% SUV from 4D-PET image defined by respiratory phase from 25% inhalation to 25% exhalation, and GTV from 4D-CT with the same phase is shown below 0.6 cm in maximum. Thus, it is better to use 4D-PET images than conventional PET images for applying MTV to gated RT. From the result that VOI of 5% SUV from 4D-PET agrees well with reference image of 4D-CT in all direction, and the recommendation from department of nuclear medicine that 30% SUV be advised for defining tumor range, it is found that using less than 30%SUV will be more accurate and practical to apply MTV for respiratory gated radiotherapy.

• Investigative Magnetic Resonance Imaging
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• v.18 no.1
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• pp.52-58
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• 2014

Purpose : To establish a pH measurement system for a mouse tumor study using a clinical scanner, to develop the $^1H$ and 31P radio frequency (RF) coil system and to test pH accuracy with phantoms. Materials and Methods: The $^1H$ and the $^{31}P$ surface coils were designed to acquire signals from mouse tumors. Two coils were positioned orthogonally for geometric decoupling. The pH values of various pH phantoms were calculated using the $^1H$ decoupled $^{31}P$ MR spectrum with the Henderson-Hasselbalch equation. The calculated pH value was compared to that of a pH meter. Results: The mutual coil coupling was shown in a standard $S_{12}$. Coil coupling ($S_{12}$) were -73.0 and -62.3 dB respectively. The signal-to-noise ratio (SNR) obtained from the homogeneous phantom $^1H$ image was greater than 300. The high resolution in vivo mice images were acquired using a $^{31}P$-decoupled $^1H$ coil. The pH values calculated from the $^1H$-decoupled $^{31}P$ spectrum correlated well with the values measured by pH meter ($R^2$=0.97). Conclusion: Accurate pH values can be acquired using a $^1H$-decoupled $^{31}P$ RF coil with a clinical scanner. This two-surface coil system could be applied to other nuclear MRS or MRI.

• Korean Chemical Engineering Research
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• v.44 no.4
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• pp.410-416
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• 2006

For highly efficient operation of a Bunsen process section in an iodine-sulfur thermochemical hydrogen production cycle using nuclear heat, the process characteristics of $H_2SO_4-HI-H_2-O-I_2$ mixture system for separating into two liquid phases ($H_2SO_4$-rich phase and $HI_x$-rich phase) and the distribution of $H_2O$ to each phase were investigated.The experiments for process variables were carried out in the temperature range, from 298 to 353 K, and in the $H_2SO_4/HI/H_2O/I_2$ molar ratio of 1/2/14~20/0.5~8.0. As the results, for the $SO_2-I_2-H_2O$ Bunsen reaction system, the ranges between the starting point and the saturation point for two liquid phases separation were determined by calculation. The best result for the minimization of impurities (HI and $I_2$ in $H_2SO_4$ phase and $H_2SO_4$ in $HI_x$ phase) in each phase was obtained in an optimum condition with the highest temperature of 353 K and the highest $I_2$ molar composition. In this condition, the $HI/H_2SO_4$ molar ratio in the $H_2SO_4$-rich phase and the $H_2SO_4/HI_x$ molar ratio in the $HI_x$-rich phase were 0.024 and 0.028, respectively. For the distribution of $H_2O$ to each phase, it is appeared that the affinity between $HI_x$ and $H_2O$ was more superior to that between $H_2SO_4$ and $H_2O$. The affinity between $HI_x$ and $H_2O$ was decreased with increasing temperature but increased with increasing $I_2$ molar composition.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.12 no.10
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• pp.4418-4424
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• 2011

This study is aimed to assess the effect of the gamma ray of 511keV energy which is emitted from phantom where the positron emission radionuclide was injected on X-ray CT image. As a scanning method, the CT number and pixel value of the reference image where water was injected(0 mCi), and those acquired by changing the capacity of 18F(Fluorine), positron emission radionuclide, into 1 mCi, 2 mCi, 5 mCi, and 10 mCi were measured. As a result of measuring the CT number(HU) of the phantom image where the positron emission radionuclide($^{18}F$) was injected, there were reference water ($-7.58{\pm}0.66$ HU), 1 mCi($-9.85{\pm}0.50$ HU), 2 mCi($-10.27{\pm}0.21$ HU), 5 mCi($-11.31{\pm}0.66$ HU), and 10 mCi($-13.47{\pm}0.38$ HU). Compared with the image where it was filled with water, there was a reduction of 5.89 Hu in 10 mCi, 3.73 in 5 mCi, 2.69 HU in 2 mCi, and 2 HU in 1 mCi. As for the pixel value of the phantom image, there were reference water ($-2.70{\pm}0.75$), 1 mCi($-4.72{\pm}0.58$), 2 mCi($-6.01{\pm}0.78$), 5 mCi($-6.10{\pm}0.84$), and 10 mCi($-8.20{\pm}0.60$). Compared with the reference image, there was a reduction of 5.50 in 10 mCi, 3.40 in 5 mCi, 3.10 in 2 mCi, and 2.02 in 1 mCi. Through this experiment, it was indicated that, with the increase in the dose of the positron emission radionuclide($^{18}F$), the CT number and the pixel value of the image reduced proportionally, and the width of reduction showed a similar value, too. Accordingly, according to the degree of change in X-ray CT image due to the positron emission radionuclide in the quality control item of PET/CT, the proper standard should be established and it should be periodically managed.

• The Journal of Korean Medicine
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• v.31 no.1
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• pp.130-137
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• 2010

Objectives: So far it has been reported that acupuncture increases cerebral blood supply and stimulates the functional activity of brain nerve cells. Previous studies have demonstrated that frequently used electro-acupuncture (EA) therapies for stroke increased regional cerebral blood flow (rCBF) in normal volunteers. Though ST 36-ST 41 EA is another prevailing therapy for stroke, there had been no report about its effect on rCBF. This study was to evaluate the effect of ST 36-ST 41 EA on rCBF in normal volunteers using single photon emission computed tomography (SPECT) and statistical parametric mapping (SPM). Methods: In the resting state, $^{99m}Tc$-ECD brain SPECT scans were performed on 10 normal volunteers (5 males, 5 female, mean age $23.6{\pm}0.5$ years). On the other study day, 7 days after the resting examination, 15 minutesEA were applied at ST 36 and ST 41 on the right side of the subjects. Immediately after ST36-ST41 EA, the second SPECT images were obtained in the same manner as the resting state. Significant increases and decreases of rCBF after EA were estimated by comparing their SPECT images with those of the resting state using paired t statistics at every voxel, which were analyzed by SPM with a threshold of p = 0.01, uncorrected (extent threshold: k=100 voxels). Results: EA applied at the right ST36-ST41 significantly increased rCBF in the right inferior parietal lobule (Brodmann area [BA] 40), right retrosubicular area (BA 48), left inferior parietal lobule (BA 40), left middle temporal gyrus (BA 21), left fusiform gyrus (BA 37), left inferior parietal lobule (BA 39), left inferior temporal gyrus (BA 20), and left somatosensory association cortex (BA 7). However, right ST36-ST41 EA significantly decreased rCBF in the right parahippocampal gyrus (BA 35), right cerebellum, left frontopolar area (BA 10), left orbitofrontal area (BA 11), left dorsolateral prefrontal cortex (BA 9), and left dorsal anterior cingulate cortex (BA 32). Conclusions: These results demonstrate that rightST36-ST41 EA increased rCBF prominently in both inferior parietal lobule (BA 40) and right retrosubicular area (BA 48), which suggest that there be correlation between specific EA and corresponding rCBF.

• Ocean and Polar Research
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• v.37 no.4
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• pp.341-356
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• 2015

A nation has a sovereign right to develop and use its natural resources according to its policies with regard to development and the relevant environment. A nation also has an obligation not to harm other countries or damage environments of neighboring countries as consequences of such actions of developments or use of natural resources. However, international precedents induce a nation to take additional actions not to cause more damages from the specific acts causing environmental damages beyond national borders, when such acts have economic and social importance. That is to say that there is a tendency to resolve such issues in a way to promote the balance between the mutual interests by allowing such actions to continue. A solution to China's Three Gorges Dam dilemma based on a soft law approach is more credible than relying on a good faith approach of national responsibilities and international legal proceedings since the construction and operation of the dam falls within the category of exercising national sovereign rights. If a large scale construction project such as the Three Gorges Dam or operation of a nuclear power plant causes or may cause environmental damage beyond the border of a nation engaged in such an undertaking, countries affected by this undertaking should jointly monitor the environmental effects in a spirit of cooperation rather than trying to stop the construction and should seek cooperative solutions of mutual understanding to establish measures to prevent further damages. If China's Three Gorges Dam construction and operation cause or contain the possibility of causing serious damages to marine environment, China cannot set aside its national responsibility to meet international obligations if China is aware of or knows about the damage that has occurred or may occur but fail to prevent, minimize, reverse or eliminate additional chances of such damages, or fails to put in place measures in order to prevent the recurrence of such damages. However, Korea must be able to prove a causal relationship between the relevant actions and resulting damages if it is to raise objections to the construction or request certain damage-prevention actions against crucial adverse effects on the marine environment out of respect for China's right to develop resources and acts of use thereof. Therefore, it is essential to cumulate continuous monitoring and evaluations information pertaining to marine environmental changes and impacts or responses of affected waters as well as acquisition of scientific baseline data with observed changes in such baseline. As China has adopted a somewhat nonchalant attitude toward taking adequate actions to protect against marine pollution risks or adverse effects caused by the construction and operation of China's Three Gorges Dam, there is a need to persuade China to adopt a more active stance and become involved in the monitoring and co-investigation of the Yellow Sea in order to protect the marine environment. Moreover, there is a need to build a regular environmental monitoring system that includes the evaluation of environmental effects beyond borders. The Espoo Convention can serve as a mechanism to ease potential conflicts of national interest in the Northeast Asian waters where political and historical sensitivities are acute. Especially, the recent diplomatic policy advanced by Korea and China can be implemented as an important example of gentle cooperation as the policy tool of choice is based on regional cooperation or cooperation between different regions.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.20 no.4
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• pp.317-327
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• 1987

As a series of studies on the suitability as a second intermediate host of Clonorchis sinensis, artificial infection experiments were applied to Tilapia mossambica. And then, in order to elucidate the defence mechanism of the fish to Clonorchis, clonorchicidal substance in the epidermal mucus of the fish was isolated by silica gel column and thin layer chromatography and analyzed for its chemical structure by UV, IR and NMR-spectroscopy. The results obtained are summarized as follows: 1. The cercariae which attempted to contact with the fish in the water were observed under stereomicroscope. After contact, the cercariae began to separate their tail from the body after several minutes and then the number increased to $80\%$ more than 10 minutes after the encounter. But very few cercariae could actually invade the epidermis of the fish. 2. The fish were reared with Parafossarulus manchouricus which were shedding numerous cercariae of Clonorchis in the aquarium for 24 hours. Only a few cercariae could invade the epidermis but most of the invaded cercariae died out before forming their cysts. Very few number of the remaining encysted cercariae were also found to be in a state of suspended animation within 42 hours. 3. In the cases of the control fish, Pseudorasbora parva, numerous cercariae of Clonorchis were found to invade the fish through the epidermis under stereomicroscope. Then many metacercariae of Clonorchis were also found in the fish while they were kept in the aquarium. 4. A sample of the epidermal mucus of Tilapia mossambica was extracted with ethly ether 6 times repeatedly. In silica gel column chromatography, using petroleum ether: chloroform/30:70(v/v) as a first solvent and MeOH as a second solvent, the extract was fractionated into the yellow and brownish red solutions in the first solvent and the clonorchicidal brownish yellow solution in the second sovent. 5. The clonorchicidal brownish yellow solution was added to petroleum ether, and the mixture was stored for 5 days at $5^{\circ}C$ and was, then, separated into supernatant fraction and precipitate. Ten mg/ml of the supernatant fraction killed, in vitro, the excysted metacercariae in 45 minutes but the precipitate in 600 minutes. 6. In silica gel column chromatography, using acetone: benzene/10:90(v/v) as a solvent, the more clonorchicidal supernatant fraction was fractionated into the first fraction with Rf. 0.2966 and the second fraction with Rf. 0.072. In vitro, 10mg/ml of the first fraction killed the excysted metacercariae in 28 minutes, the second fraction in 80 minutes and the first fraction was, therefore, determined to be a final clonorchicidal substance. 7. By this purification procedures, the most clonorchicidal substance from the epidermal mucus of Tilapia mossambica was purified 71-folds with $0.2075\%$ yield. Infra red, nuclear magnetic resonance and ultraviolet spectrometric analysis of the purified substance revealed that the substance is linoleic acid. According to the results of the present studies it seemed that this species can not serve as a proper intermediate host of Clonorchis sinensis, and that defence mechanism to the fluke seems to be correlated with linoleic acid in the epidermal mucus of this species.

• Microbiology and Biotechnology Letters
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• v.43 no.1
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• pp.45-55
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• 2015

This study was carried out to demonstrate the anti-inflammatory effect of tuna oil (TO) using LPS-induced inflammation responses and mouse models. First, nitric oxide (NO) and pro-inflammatory cytokines levels were suppressed up to 50% with increasing concentrations of TO without causing any cytotoxicity. Also, the expression of a variety of proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB), was suppressed in a dosedependent manner by treatment with TO. Furthermore, TO also inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs), including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 protein kinase (p38). Moreover, in in vivo testing the formation of ear edema was reduced at the highest dose tested compared to that in the control, and a reduction of ear thickness and the number of mast cells was observed in histological analysis. In acute toxicity test, no mortalities occurred in mice administrated 5,000 mg/kg body weight of TO over a two-week observation period. Our results suggest that TO has a considerable anti-inflammatory property through the suppression of inflammatory mediator productions and that it could prove to be useful as a potential anti-inflammatory therapeutic material.