• Title/Summary/Keyword: comparative toxicity

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Affecting Factors of Lung Disease and Classification of Exposure Rating of Applicants for Injuries from Humidifier Disinfectants (가습기살균제 피해신청자들의 노출등급 분류 및 폐질환 발생 영향요인 분석)

  • Gihong, Min;Junghyun, Shin;Eun-Kyung, Jo;Dayoung, Jeong;Jiyoon, Ryu;Dongjun, Kim;Jaemin, Woo;Sungho, Bae;Jihun, Shin;Seula, Lee;Yoon-Hyeong, Choi;Wonho, Yang
    • Journal of Environmental Health Sciences
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    • v.48 no.6
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    • pp.324-330
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    • 2022
  • Background: Lung injuries due to exposure to humidifier disinfectants (HDs) were reported in 2011 in South Korea. As a result of the government's epidemiological investigation and toxicity test study, it was found that HDs caused health damage such as lung disease. Objectives: The purpose of this study was to classify HD exposure ratings and analyze the affecting factors that could identify the relationship with lung disease. Methods: Exposure assessment for HDs was conducted using a questionnaire during face-to-face interviews with the applicants. Ratings of high exposure (Class 1) and low exposure (Class 2) were cross-tabulated with clinical ratings (acceptable and unacceptable). Logistic regression analysis was carried out by setting the clinical rating of lung disease as a dependent variable and the socio-demographic and exposure characteristics obtained through the questionnaire as independent variables. Results: The concentration in air of polyhexamethylene guanidine (PHMG) was 71.96±107.47 ㎍/m3, and the exposure concentration was 15.21±23.28 ㎍/m3 . The exposure rating was overestimated with 97.1% of affected subjects having high exposure using margin of exposure (MOE), but only 9.9% matching the clinical class. In the overestimated group, it could be explained by the fact that the exposure time was long and the subjects had already recovered from damage symptoms. As a result of logistic regression analysis, ten variables were found to be significant influencing factors. Conclusions: A new exposure rating could be calculated based on the MOE, and factors affecting lung disease could be estimated through comparative evaluation with the clinical rating.

Comparative Study of the Neuroprotective Effect of Sihogyeji-tang, Sihosogan-tang, and Sihocheonggan-tang on an MPTP-Induced Parkinson's Disease Mouse Model (MPTP로 유도된 파킨슨병 생쥐 모델에 대한 시호계지탕, 시호소간탕, 시호청간탕의 신경세포 보호 효과 비교 연구)

  • Ji Eun Seo;Hanul Lee;Chang-Hwan Bae;Dong Hak Yoon;Hee-Young Kim;Seungtae Kim
    • Korean Journal of Acupuncture
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    • v.40 no.3
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    • pp.90-98
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    • 2023
  • Objectives : Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide and is characterized by the loss of the dopaminergic neurons in the substantia nigra (SN). In a previous in vitro study, we demonstrated that Sihogyeji-tang (SG), Sihosogan-tang (SS), and Sihocheonggan-tang (SC) have the potential to be candidate medicines for PD. This study aimed to compare the neuroprotective effect of SG, SS, and SC using 1-methyl-4-phenyl-1,2,3,6-tetrahydrophridine (MPTP)-induced PD mouse model. Methods : Eight-week-old male C57BL/6 mice were intraperitoneally administered with 30 mg/kg of MPTP for 5 days and orally administered SG, SS and SC for 12 days from the first MPTP injection. Motor function was assessed using the pole test and the rotarod test. Dopaminergic neuronal survival in the SN and striatum was evaluated through tyrosine-hydroxylase immunohistochemistry. Results : MPTP administration resulted in behavioral impairment and dopaminergic neuronal death in the SN and striatum. In the pole test, treatment with SG, SS, and SC alleviated the MPTP-induced motor dysfunction on day 5 and 12. In the rotarod test, SS and SG alleviated the MPTP-induced motor dysfunction on day 5, while only SS showed improvement on day 12. SS and SG significantly protected dopaminergic neurons in the SN from MPTP toxicity, and all three compounds (SG, SS, and SC) showed significant protection in the striatum. Notably, SS demonstrated superior efficacy in suppressing MPTP-induced motor dysfunction and dopaminergic neuronal death compared to SG and SC. Conclusions : These findings suggest that SS is the most effective formula among SG, SS, and SC for PD, indicating its potential role in the treatment of PD.

Role of Salmonella Typhimurium SlyA in Regulating the Expression of VirulenceFactors Related to Survival in Macrophages (대식세포 내 생존과 관련된 독성인자 발현 조절에서의 Salmonella Typhimurium SlyA의 역할)

  • Yeo bin Kim;Jeong-eun Baek;Yeon Ha Kim;Young Hee Kim;Ah Young Yoo;Ho Young Kang
    • Journal of Life Science
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    • v.34 no.2
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    • pp.79-85
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    • 2024
  • SlyA is known as a transcriptional regulator that regulates the expression of hemolysin (HlyE) in E. coli, a member of the Enterobacteriaceae family such as Salmonella. However, Salmonella has the slyA gene but lacks the hlyE gene. Then, because we were curious about the role of SlyA in Salmonella, we constructed and explored a mutant strain with a deletion of the slyA gene. S. Typhimurium CK295 (ΔslyA) was constructed using an allelic exchange approach. In a comparative analysis between the wild-type and the CK295 strain, no significant differences were observed in growth characteristics, motility, total protein analyses, and secreted protein analyses. However, the CK295 strain exhibited slightly reduced biofilm formation compared to the wild-type. Interestingly, as a result of comparing the survival ability in macrophages, the mutant strain showed a 60% decrease in survival ability compared to the wild-type. To evaluate toxicity in mice, mortality was measured after oral administration to 6-week-old BALB/c mice. As a result, the LD50 value of the CK295 (ΔslyA) was more than 100 times higher than that of wild-type S. Typhimurium 𝜒3339 in BALB/c. In conclusion, SlyA is presumed to regulate the expression of genes encoding virulence factors involved in the in vivo survival of Salmonella.

The Classification System and Information Service for Establishing a National Collaborative R&D Strategy in Infectious Diseases: Focusing on the Classification Model for Overseas Coronavirus R&D Projects (국가 감염병 공동R&D전략 수립을 위한 분류체계 및 정보서비스에 대한 연구: 해외 코로나바이러스 R&D과제의 분류모델을 중심으로)

  • Lee, Doyeon;Lee, Jae-Seong;Jun, Seung-pyo;Kim, Keun-Hwan
    • 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.

Clinical Efficacy of Belotecan (CKD-602), Newly Developed Camptothecin Analog, in the 2nd Line Treatment of Relapsed Small Cell Lung Cancer (재발된 소세포폐암환자에서 이차 약제로 사용되는 Belotecan (CKD-602)의 임상적 효용성)

  • Ban, Hee-Jung;Oh, In-Jae;Kim, Kyu-Sik;Ju, Jin-Yung;Kwon, Yong-Soo;Kim, Yu-Il;Lim, Sung-Chul;Kim, Young-Chul
    • Tuberculosis and Respiratory Diseases
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    • v.66 no.2
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    • pp.93-97
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    • 2009
  • Background: Belotecan (Camtobell, CKD-602, Chongkundang Pharm., Korea), a camptothecin derivative, has anticancer effects by inhibiting topoisomerase I such as topotecan. This study observed the response, survival and toxicity of belotecan monotherapy after the failure of etoposide and platinum (EP). Methods: Forty nine small cell lung cancer (SCLC) patients (M/F=41/8; age, 64.5${\pm}$7.6 (mean${\pm}$SD) years), who failed in their first line chemotherapy were enrolled in this study. Twenty one SCLC patients showed relapsed lung cancer more than 90 days after their priorEP chemotherapy (sensitive relapse group, SR) and 28 patients relapsed within 90 days (refractory relapse group, RR). Results: The response rate was 25%. Eleven patients showed partial responses and 5 patients could not be checked. The response rate of the SR and RR patients was similar. The relative dose intensity was lower in the responders (78${\pm}$15%) than non-responders (83${\pm}$13%, p=0.03). The median survival time (MST) was 10.3 months (290 days). The MST of the non-responders and responders was 186 days (95% CI; 67-305) and 401 days (95% CI; 234-568, p=0.07), respectively. The median progression free survival (MPFS) was similar in the SR (79 days) and RR (67 days) patients. Grade 3-4 neutropenia, anemia, and thrombocytopenia were observed in 59.6%, 12.8% and 23.4% of patients, respectively. Conclusion: The efficacy and survival were demonstrated in the second-line setting. However, a randomized comparative trial with topotecan will be needed.

Comparative Study of Toxic Effects of Anatase and Rutile Type Nanosized Titanium Dioxide Particles in vivo and in vitro

  • Numano, Takamasa;Xu, Jiegou;Futakuchi, Mitsuru;Fukamachi, Katsumi;Alexander, David B.;Furukawa, Fumio;Kanno, Jun;Hirose, Akihiko;Tsuda, Hiroyuki;Suzui, Masumi
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.929-935
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    • 2014
  • Two types of nanosized titanium dioxide, anatase ($anTiO_2$) and rutile ($rnTiO_2$), are widely used in industry, commercial products and biosystems. $TiO_2$ has been evaluated as a Group 2B carcinogen. Previous reports indicated that $anTiO_2$ is less toxic than $rnTiO_2$, however, under ultraviolet irradiation $anTiO_2$ is more toxic than $rnTiO_2$ in vitro because of differences in their crystal structures. In the present study, we compared the in vivo and in vitro toxic effects induced by $anTiO_2$ and $rnTiO_2$. Female SD rats were treated with $500{\mu}g/ml$ of $anTiO_2$ or $rnTiO_2$ suspensions by intra-pulmonary spraying 8 times over a two week period. In the lung, treatment with $anTiO_2$ or $rnTiO_2$ increased alveolar macrophage numbers and levels of 8-hydroxydeoxyguanosine (8-OHdG); these increases tended to be lower in the $anTiO_2$ treated group compared to the $rnTiO_2$ treated group. Expression of $MIP1{\alpha}$ mRNA and protein in lung tissues treated with $anTiO_2$ and $rnTiO_2$ was also significantly up-regulated, with $MIP1{\alpha}$ mRNA and protein expression significantly lower in the $anTiO_2$ group than in the $rnTiO_2$ group. In cell culture of primary alveolar macrophages (PAM) treated with $anTiO_2$ and $rnTiO_2$, expression of $MIP1{\alpha}$ mRNA in the PAM and protein in the culture media was significantly higher than in control cultures. Similarly to the in vivo results, $MIP1{\alpha}$ mRNA and protein expression was significantly lower in the $anTiO_2$ treated cultures compared to the $rnTiO_2$ treated cultures. Furthermore, conditioned cell culture media from PAM cultures treated with $anTiO_2$ had less effect on A549 cell proliferation compared to conditioned media from cultures treated with $rnTiO_2$. However, no significant difference was found in the toxicological effects on cell viability of ultra violet irradiated $anTiO_2$ and $rnTiO_2$. In conclusion, our results indicate that $anTiO_2$ is less potent in induction of alveolar macrophage infiltration, 8-OHdG and $MIP1{\alpha}$ expression in the lung, and growth stimulation of A549 cells in vitro than $rnTiO_2$.

Monitoring and Risk Assessment of Pesticide Residues in Herbal Medicines in Incheon (인천광역시 유통 한약재의 잔류농약 실태 조사 및 위해평가)

  • Min-jeong Kang;Sung-Hee Kwon;Sun-Hoi Kim;Mi-Sook Yeom;Byung-Kyu Park;Hee-jeong Lee;Ji-Hyeung Kim;Kwang-sig Joo;Myung-je Heo;Mun-ju Kwon
    • Journal of Food Hygiene and Safety
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    • v.39 no.2
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    • pp.118-127
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    • 2024
  • This study investigated the levels of 345 pesticide residues in 50 herbal medicines sold in Incheon metropolitan city to determine their safety. Pesticide residues are harmful substances that can cause serious health problems owing to their toxicity and carcinogenicity. The analysis of pesticide residues in the samples was conducted using the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method, known for its high analysis efficiency, to analyze a wide range of pesticides for which no standards have been set. The analysis was cross-validated with the pretreatment method outlined in the Korea Pharmacopoeia. Among the 50 samples encompassing 24 different herbs, 22 pesticide residues were detected in 24 samples, covering 7 distinct herbs, resulting in a detection rate of 48%. It is noteworthy that, except for two cases, all detected pesticides were those for which no standards were set. However, after conducting a risk evaluation considering the daily dosage of herb, it was determined that the levels of pesticide residues were within safe limits. Pesticides with high frequency within the same category of herbs were detected, indicating the necessity for continuous monitoring and regulation. In addition, comparative analysis using the pretreatment method outlined in the Korean Pharmacopoeia, yielded similar results, suggesting the possibility of analyzing pesticide residues in herbs using the QuEChERS method. The study emphasizes the importance of continuous monitoring of pesticide residues in herbs and the development of high-efficiency reliability analysis methods should continue to ensure consumer safety.

A Prospective Randomized Comparative Clinical Trial Comparing the Efficacy between Ondansetron and Metoclopramide for Prevention of Nausea and Vomiting in Patients Undergoing Fractionated Radiotherapy to the Abdominal Region (복부 방사선치료를 받는 환자에서 발생하는 오심 및 구토에 대한 온단세트론과 메토클로프라미드의 효과 : 제 3상 전향적 무작위 비교임상시험)

  • Park Hee Chul;Suh Chang Ok;Seong Jinsil;Cho Jae Ho;Lim John Jihoon;Park Won;Song Jae Seok;Kim Gwi Eon
    • 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.

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