• Journal of the Korean Chemical Society
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• v.51 no.1
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• pp.43-50
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• 2007

Liposomes having particle size from several tens to hundreds nanometers are efficient carriers for injectable drug delivery. Enhancement of liposome stability in bloodstream has been studied because of its relatively short circulation time and fast clearance from human body by reticuloendothelial system (RES) in blood vessel. In this study, new disaccharide-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) derivatives in which lactose or sucrose as the disaccharide molecule was conjugated covalently to DSPE were synthesized. Liposomes of which surface had disaccharide molecules were prepared by incorporating the disaccharide-DSPE into liposomes as one of their lipid components. Particle size of the prepared liposomes was approximately 100 nm. The liposomes of which surface were modified with the disaccharide-DSPE showed -25 mV of zeta potential value due to the presence of hydroxyl groups on their surface, while the unmodified control liposomes showed -10 mV of zeta potential value. Loading efficiency of model drug, doxorubicin, into liposomes was about 90%. Stability of the disaccharide-modified liposomes in vitro was evaluated by monitoring the amount of protein adsorption and particle size of the liposomes in serum. Disaccharide-modified liposomes were more stable in serum than unmodified control liposomes or polyethyleneglycol (PEG)-modified liposomes due to less adsorption of serum protein and hence less increase of their particle size. The liposomes of which surface was modified with disaccharide-DSPE conjugate can be used as long-circulating carriers for drugs having high toxicity or short half-life time due to their enhanced stability in blood circulatory system.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.8
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• pp.1166-1173
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• 2014

This study investigated the detoxification effects of enzymatic hydrolysate from oyster on acetaminophen-induced toxicity using HepG-2 cells. Oyster hydrolysate was made with 1% Protamex and 1% Neutrase after treatment with transglutaminase (TGPN) or without (PN). Two types of oyster hydrolysate were added to human-derived HepG-2 hepatocytes damaged by acetaminophen, after which the survival rate of HepG-2 cell was measured. In addition, glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities in the culture media were evaluated. The survival rates of HepG-2 cells were $136.2{\pm}1.4%$ at $100{\mu}g/mL$ of TGPN and $179.6{\pm}3.8%$ at $200{\mu}g/mL$ of TGPN. These cell survival rates were higher compared to that of the negative control group ($60.7{\pm}3.2%$) treated only with acetaminophen. GOT activity was $38.3{\pm}0.2$ Karmen/mL in the negative control group, whereas it was $19.9{\pm}0.5$ for TGPN ($200{\mu}g/mL$) and $22.0{\pm}2.4$ Karmen/mL for PN ($200{\mu}g/mL$). GOT and GTP activities were shown to be dependent on TGPN concentration, and significant reduction in activities could be conformed. The detoxification efficacy of TGPN was higher compared to that of PN. These results suggest that oyster hydrolysate has potential as a healthy food or pro-drug for liver protection.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.100-106
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• 2001

Purpose : We performed a retrospective analysis to compare short term results of induction chemotherapy-radiotherapy versus concurrent chemo-radiotherapy in patients with locally advanced nasopharyngeal carcinoma. Materials and Methods : From Oct. 1989 to May 1998, 62 patients with locally advanced nasopharyngeal carcinoma were treated with induction chemotherapy followed by radiotherapy (induction group) or concurrent chemo-radiotherapy (concurrent group). Induction chemotherapy was done for 50 patients, and concurrent chemotherapy for 12 patients. Age, sex, performance status, and pathologic types were evenly distributed between two groups. Stage distribution showed $32\%$ with IIB, $32\%$ with III, and $38\%$ with IV in induction group, and $50\%,\;33.3\%,\;and\;16.7\%$ in concurrent group, respectively. Chemotherapy regimen was CF (cisplatin and 5-FU) in both groups, and drug delivery method also same. Cisplatin $100\;mg/m^2$ was intravenously infused on day 1, and 5-FU $1,000\;mg/m^2$ on day $2\~6$. This was repeated at 3 weeks interval. At the end of radiotherapy, total cycles of chemotherapy were $1\~3$ (median 2) in both groups. Conventionally fractionated radiotherapy with daily fraction size $1.8\~2.0\;Gy$ and 5 fractions/week was done. Total dose was $69.4\~86\;Gy$(median 73.4 Gy) for induction group, and $69.4\~75.4\;Gy$ (median 70.8 Gy) for concurrent group. Follow-up time was $9\~116$ months (median 40.5 months) for induction group, $14\~29$ months (median 21 months) for concurrent group, respectively. Results : Overall 2 year survival rate (2YSR) for all patients was $78.7\%$. According to treatment modality, 2YSR were $77\%$ for induction group, $87\%$ for concurrent group (p>0.05). 2 year disease-free survival rate were $56\%$ and $81\%\;(p>0.05)$, respectively. Complete response to treatment were $75.5\%$ for induction group and $91.7\%$ for concurrent group, but there was no statistical difference. The incidence of grade $3\~4$ hematologic toxicity during radiotherapy was not differ between two groups, but grade 2 leukopenia was more frequent in concurrent group $(18\%\;vs\;66.7\%)$Grade $3\~4$ mucositis was more frequent in concurrent group $(4.0\%\;vs\;33.3\%)$. Overall incidence of grade $3\~4$ acute toxicity during radiotherapy was more frequent in concurrent group $(6.0\%\;vs\;41.7\%,\;p=0.005)$. Conclusion : Concurrent chemo-radiotherapy showed a trend of improvement in short-term survival and in treatment response when compared with induction chemotherapy-radiotherapy in locally advanced nasopharyngeal carcinoma. More controlled randomized trial are needed.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.127-135
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• 2001

Purpose : This study is a prospective randomized clinical trial comparing the efficacy and complication of anti-emetic drugs for prevention of nausea and vomiting after radiotherapy which has moderate emetogenic potential. The aim of this study was to investigate whether the anti-emetic efficacy of ondansetron $(Zofran^{\circledR})$ 8 mg bid dose (Group O) is better than the efficacy of metoclopramide 5 mg lid dose (Group M) in patients undergoing fractionated radiotherapy to the abdominal region. Materials and Methods : Study entry was restricted to those patients who met the following eligibility criteria: histologically confirmed malignant disease; no distant metastasis; performance status of not more than ECOG grade 2; no previous chemotherapy and radiotherapy. Between March 1997 and February 1998, 60 patients enrolled in this study. All patients signed a written statement of informed consent prior to enrollment. Blinding was maintained by dosing identical number of tablets including one dose of matching placebo for Group O. The extent of nausea, appetite loss, and the number of emetic episodes were recorded everyday using diary card. The mean score of nausea, appetite loss and the mean number of emetic episodes were obtained in a weekly interval. Results : Prescription error occurred in one patient. And diary cards have not returned in 3 patients due to premature refusal of treatment. Card from one patient was excluded from the analysis because she had a history of treatment for neurosis. As a result, the analysis consisted of 55 patients. Patient characteristics and radiotherapy characteristics were similar except mean age was $52.9{\pm}11.2$ in group M, $46.5{\pm}9.5$ in group O. The difference of age was statistically significant. The mean score of nausea, appetite loss and emetic episodes in a weekly interval was higher in group M than O. In group M, the symptoms were most significant at 5th week. In a panel data analysis using mixed procedure, treatment group was only significant factor detecting the difference of weekly score for all three symptoms. Ondansetron $(Zofran^{\circledR})$ 8 mg bid dose and metoclopramide 5 mg lid dose were well tolerated without significant side effects. There were no clinically important changes In vital signs or clinical laboratory parameters with either drug. Conclusion : Concerning the fact that patients with younger age have higher emetogenic potential, there are possibilities that age difference between two treatment groups lowered the statistical power of analysis. There were significant difference favoring ondansetron group with respect to the severity of nausea, vomiting and loss of appetite. We concluded that ondansetron is more effective anti-emetic agents in the control of radiotherapy-induced nausea, vomiting, loss of appetite without significant toxicity, compared with commonly used drug, i.e., metoclopramide. However, there were patients suffering emesis despite the administration of ondansetron. The possible strategies to improve the prevention and the treatment of radiotherapy-induced emesis must be further studied.

• Journal of Intelligence and Information Systems
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• v.26 no.3
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• pp.127-147
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• 2020

The world is suffering from numerous human and economic losses due to the novel coronavirus infection (COVID-19). The Korean government established a strategy to overcome the national infectious disease crisis through research and development. It is difficult to find distinctive features and changes in a specific R&D field when using the existing technical classification or science and technology standard classification. Recently, a few studies have been conducted to establish a classification system to provide information about the investment research areas of infectious diseases in Korea through a comparative analysis of Korea government-funded research projects. However, these studies did not provide the necessary information for establishing cooperative research strategies among countries in the infectious diseases, which is required as an execution plan to achieve the goals of national health security and fostering new growth industries. Therefore, it is inevitable to study information services based on the classification system and classification model for establishing a national collaborative R&D strategy. Seven classification - Diagnosis_biomarker, Drug_discovery, Epidemiology, Evaluation_validation, Mechanism_signaling pathway, Prediction, and Vaccine_therapeutic antibody - systems were derived through reviewing infectious diseases-related national-funded research projects of South Korea. A classification system model was trained by combining Scopus data with a bidirectional RNN model. The classification performance of the final model secured robustness with an accuracy of over 90%. In order to conduct the empirical study, an infectious disease classification system was applied to the coronavirus-related research and development projects of major countries such as the STAR Metrics (National Institutes of Health) and NSF (National Science Foundation) of the United States(US), the CORDIS (Community Research & Development Information Service)of the European Union(EU), and the KAKEN (Database of Grants-in-Aid for Scientific Research) of Japan. It can be seen that the research and development trends of infectious diseases (coronavirus) in major countries are mostly concentrated in the prediction that deals with predicting success for clinical trials at the new drug development stage or predicting toxicity that causes side effects. The intriguing result is that for all of these nations, the portion of national investment in the vaccine_therapeutic antibody, which is recognized as an area of research and development aimed at the development of vaccines and treatments, was also very small (5.1%). It indirectly explained the reason of the poor development of vaccines and treatments. Based on the result of examining the investment status of coronavirus-related research projects through comparative analysis by country, it was found that the US and Japan are relatively evenly investing in all infectious diseases-related research areas, while Europe has relatively large investments in specific research areas such as diagnosis_biomarker. Moreover, the information on major coronavirus-related research organizations in major countries was provided by the classification system, thereby allowing establishing an international collaborative R&D projects.

• Herbal Formula Science
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• v.15 no.1
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• pp.185-197
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• 2007

Objective : This study was conducted to investigate the effects of Hwangryunhaedok-Tang and Geongangbuja-Tang on the change of interleukin-6 (IL-6) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) level induced by LPS I.C.V. injection in mice. Method : We devided group into 6 mice and 6 mice were assingned to each group. In the normal group only saline was administered intragastrically, and in the control group LPS was injected intracerebroventricularly 1 hr after intragastric administration of saline. In the experiment groups Hwangryunhaedok-Tang(0.5g/kg, 1.0g/kg, 3.0g/kg) was administered intragastrically to mice 1 hr prior to LPS(100mg/mouse) I.C.V. injection.. Also Geongangbuja-Tang (0.5g/kg, 1.0g/kg, 3.0g/kg) was administered intragastrically to mice 1 hr prior to LPS(100mg/mouse) I.C.V. injection. To measure the plasma IL-6 and $TNF-{\alpha}$ level of mice, their blood samples were collected from retro-orbital plexus, immediately centrifuged at $4^{\circ}C$, and plasma was removed and stored frozen at $-83^{\circ}C$ for later determination of IL-6 and $TNF-{\alpha}$. The level of IL-6 and $TNF-{\alpha}$ production was measured by enzyme-linked immunosorbent assay in the plasma. Result : Regarding IL-6 level, The 0.5g/kg and the 1g/kg groups of Geongangbuja-Tang decreased IL-6 level. Especially the 3g/kg control group decreased IL-6 level significantly than the normal group(p<0.01). Regarding $TNF-{\alpha}$ level, the 3g/kg group of Geongangbuja-Tang decreased it significantly(p<0.05). Conclusion : These data revealed that Hwangryunhaedok-Tang might not have the anti imflammatory effect and Geongangbuja-Tang(3g/kg)might have the anti imflammatory effect by reducing the plasma IL-6 and $TNF-{\alpha}$ level in mice LPS Injection.EIM (Eighteen Incompatible Medicaments) is an important component in Oriental pharmacology and is directly related to clinical prescriptions. Medical practitioners argued that the definite cause and meaning of EIM was ambiguous and therefore debated the issue of clinical application of the EIM. This study conducted an in-depth literary research on the origin, meaning and contents of EIM with the purpose to contribute in its efforts to be used clinically. Even after thousands of years have past since establishment of Oriental medicine, EIM is still tabooed and was an obstacle that hindered ideologies. Modern herbal medicine texts claim that the use of EIM can reduce treatment effects and promote poisoning and side effects. However, since long ago, there has been medical practitioners who reject this as false. Recently, poisoning caused by EIM has been claimed to be from the toxicity of the drug itself, rather than the result of interaction between the drugs, and therefore they suggest that EIM is not a forbidden domain. In addition, EIM showed a difference in number depending on the era. However, this can be understood not as a definite number, but instead as a warning to be careful during combination of drugs for use as clinical medicine. Historically, there were very few cases in which EIM was used for clinical tests and thus, the clinical value is not, while others applied EIM directly to their bodies, which showed signs for the usefulness and potential of EIM for us. A more concrete and in-depth study must be made on EIM.

• Journal of Life Science
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• v.23 no.6
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• pp.812-824
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• 2013

Reserpine, an anti-hypertensive drug, is able to positively modulate several phenotypes associated with $A{\beta}$ toxicity in a Caenorhabditis elegans model of Alzheimer's disease (AD). We investigated into the therapeutic effects of reserpine on mammalian neurodegenerative disorders, and found that significant alteration of the key factors influencing AD was detected in Tg2576 mice after reserpine treatment for 30 days. The aggressive behavior of Tg2576 mice was significantly improved upon reserpine treatment, whereas their social contact was consistently maintained. Furthermore, the levels of $A{\beta}$-42 peptide in the hippocampus of the brain and blood serum were lower in the reserpine-treated group than in the vehicle-treated group. Among g-secretase components, the expression levels of PS-2, Pen-2, and APH-1 were slightly lower in reserpine-treated Tg2576 mice, although a significant change in nicastrin (NCT) expression was not detected. Furthermore, the serum level of nerve growth factor (NGF) increased in reserpine-treated Tg2576 mice compared with vehicle-treated mice. Among down-stream effectors of the NGF receptor TrkA signaling pathway, reserpine treatment induced elevation of TrkA phosphorylation and reduction of ERK phosphorylation. In addition, in the NGF receptor $p75^{NTR}$ signaling pathway, the expression levels of $p75^{NTR}$ and Bcl-2 were enhanced in reserpine-treated Tg2576 mice compared with vehicle-treated mice, whereas the expression level of RhoA declined. Overall, these results suggest that reserpine can help relieve AD pathogenesis in Tg2576 mice through downregulation of $A{\beta}$-42 deposition, alteration of ${\gamma}$-secretase components, and regulation of NGF metabolism.

• Journal of The Korean Society of Clinical Toxicology
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• v.2 no.2
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• pp.83-89
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• 2004

Acute poisoning is one of the diseases which need the most fastest emergency measures at the very beginning. However, at present, The Korea doesn't manage the toxication all over the country, and in particular, there is no guide to medical cure paying due regard to the traits of each area. This paper focused on the issue that the necessary data in preparing the facilities for the treatment of the poisoned patients and materials for medical treatment including antidote would have to be collected, after finding the special features of the symptoms by searching the present conditions of the poisoning in small towns next to farm villages in the North area of Youngseo, Kangwon province. This study was based on the questionnaires from 111 patients who were carried into the emergency room by the poisoning in two university hospitals of the North area of Youngseo, Kangwon, for one year, 2002. Upon investigation, the patients(111) visiting emergency room by the acute poisoning during the research period was found to be 0.37 percent of all patients(30,085) visiting emergency room. Among them, the most high percentage was given in their twenties and thirties at the rate of $39.6\%$, and the ratio($40.5\%$) of the poisoned patients after their fifties was much higher than a research($10\%$) of other areas. Many poisoned patients came to their rescue in an emergency room generally in spring and in winter, from 7 a.m. to 3 p.m. Agricultural chemical of the toxic materials had a majority at a ratio of $57.7\%$, and paraquat of the agricultural chemicals was found to have a lot of toxicity by $31.7\%$. As the trace of the toxication, the oral poisoning was common by $89.2\%$, and $55.9\%$ in the case of operating gastric lavage and nasogastric irrigation, but only $14.4\%$ for prescribing antidote. The mortality of the acute poisoned patients was $17.2\%$, and the toxication by paraquat held a majority. As a result, the acute poisoning of the North area in Youngseo, Kangwon had both of the characteristics of the rural and the city, and the patients over their fifties by the population aging had more attack of the disease than other regions. Also, with the high ratio of the toxication by the agricultural chemicals, especially, the lethal agricultural chemical was used frequently. Therefore, these dangerous situations need to find the ways to cope with.

• The Journal of Internal Korean Medicine
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• v.35 no.1
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• pp.92-105
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• 2014

Objectives : Cisplatin is a widely used cancer therapy drug. However, nephrotoxicity resulting in increased oxidative stress is a major side effect of cisplatin chemotherapy, thereby limiting its chemotherapeutic use. Lycium chinense Miller (LCM) has been used as a traditional herbal medicine in various febrile and inflammatory diseases such as night sweat, cough, nosebleed, bronchitis, pulmonary tuberculosis, etc. In this study we investigated the protective and antioxidative potential of LCM against cisplatin-induced nephrotoxicity in rats. Methods : Twenty-four 8-week-old male Wistar rats were divided into four groups: normal untreated; cisplatin treatment only; LCM 10 mg/kg plus cisplatin treatment; and LCM 30 mg/kg plus cisplatin treatment. Twenty-four hours after the last cisplatin injection, all the rats were sacrificed, and serological changes were evaluated. The levels of NF-${\kappa}B$ activity and NOX-4, $p47^{phox}$, $p22^{phox}$, COX-2, iNOS, SOD, catalase expressions were analyzed in Western blot analysis. Results : Cisplatin injection caused an increase in the BUN level, which is a reliable indicator of renal toxicity. The levels of BUN, renal ROS, and renal TBARS were significantly reduced in the LCM groups compared with the cisplatin-only groups. The levels of $p47^{phox}$ and $p22^{phox}$, which are NADPH oxidase subunits, were increased in the cisplatin-only groups, whereas they were decreased in the LCM groups. The levels of renal NF-${\kappa}B$ activity and COX-2, iNOS expressions were increased significantly in the cisplatin-only groups compared with the normal groups, whereas they were decreased in the LCM groups. Compared with the cisplatin-only groups, renal GSH and GSH/GSSG increased in the LCM groups. Also, the administration of LCM increased levels of SOD and catalase as compared with the cisplatin-only groups. Conclusions : These results suggest that LCM protects cisplatin-induced nephrotoxicity via a mechanism that may involves the inhibition of oxidative stress by the activation of antioxidants.

• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.230-240
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• 2002

Background : The majority of chemotherapy-treated small cell lung cancers(SCLC) patients eventually recur. Although many patients are in excellent physical condition at the time of recurrence, few drugs or drug combinations are capable of effecting a tumor regression in this setting. Topotecan, a topoisomerase I inhibitor, is one of the more widely studied single afents in SCLC. The aim of this study was to determine the response rate, survival and toxicity of topotecan as a second line traeatment SCLC. Materials and Methods : 19 patients with measurable SCLC, progressive during the first line chemotherapy (9 cases) or recurrent after the first line chemotherpy(10 cases), were enrolled in this study. Topotecan was administered as a 30-minute daily infusion at a dose of 1.5mg/$m^2$ for 5 consecutive days, every 3 weeks. Results : The overall response rate was 26.3%(5/19, CR 2, PR 3, SD 3, PD 11). The median survival was 24 weeks. The response rate and survival were poor in the nonresponders during first chemotherapy, those who were refractory to the first chemotherapy(recurrent within 3 months after completion of first chemotherapy) and extensive disease, but the results were not statistically significant. The toxicities were mainly hematologic and anemia grade III 1/90, leukopenia grade III 6/90 IV 4/90, thrombocytopenia grade III 1/90 IV 1/90, vomiting grade III 1/90 of cycles were occurred. There was no treatment-related deaths due to severe myelosuppression. Conclusion : Topotecan can be an active second line chemotherapeutic agent for treating SCLC.