• Archives of Pharmacal Research
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• 제29권12호
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• pp.1158-1163
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• 2006

More than 95% of lead, a environmental heavy metal, entering into blood accumulates in erythrocytes suggesting erythrocytes as an important target of lead toxicity. Recent studies reported that erythrocytes could contribute to blood coagulation via phosphatidylserine (PS) exposure in erythrocytes. However, in vivo effects of chronic lead exposure especially by drink-ing water on procoagulant activity of erythrocytes have not been studied yet. In the present study, we investigated the effects of chronic exposure of lead by drinking water on erythrocytes in rats. Groups of 40 male rats were provided with drinking water containing various concentrations of lead for 4 weeks and complete blood cell count, procoagulant activities of erythrocytes and platelets were evaluated with basic inspections on body weight and food/water consumption. The administration of lead containing drinking water increased the blood lead level (BLL) in a dose-dependent manner up to $22.39{\pm}2.26\;{\mu}g/dL$. Water consumption was significantly decreased while food consumption or body weight gain was not affected. In contrast to the previous findings with acute lead exposure, chronic lead exposure failed to increase PS exposure in erythrocytes with statistical significance although some trends of enhancement were observed. It implies that a certain adaptation might have happened in body during repeated exposure to lead, resulting in attenuation of PS exposure. With this study, we believe that a valuable information was provided for the study on the toxicological significance and the risk assessment of lead contaminated drinking water.

• 한국산업보건학회지
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• 제17권4호
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• pp.322-334
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• 2007

This study covers the investigation of the actual condition in the workplace to produce plastics products using synthetic resins and the investigation on the trends amount of the domestic production of thermoplastic resins. To analyze the monomers included in thermoplastic resins frequently used in the workplace, we analyzed thermal characteristics for test compounds using thermogravimetric analysis and did the qualitative analysis using Pyrolyzer GC-MSD & TDS GC-MSD. And then we classified the health hazard of monomers based on GHS classification criteria using information toxicity & carcinogenicity. The number of the workplace to produce plastics products among all domestic manufacturers of 73,884 was 4,391 (5.94%). The number of workers to produce plastics products among all workers of 2,522,750 in all domestic manufacturers was 104,971 (4.16%). The amount of production per year for thermoplastic resins is in the order of PP, HDPE, LDPE, PVC, ABS, PS and such compounds was producing over 1 Million ton per year each. The classification result based on GHS classification criteria for 22 main compounds included thermoplastic resins says 2 compounds of acrylonitrile, naphthalene are in Acute oral category 3 and benzene is in Acute dermal category 1. The classification results of health hazard of carcinogenicity based on IARC & ACGIH carcinogen classification says 2 compounds of benzene, vinyl chloride are in category 1A (known to be human carcinogens).

• 대한한방내과학회지
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• 제40권6호
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• pp.1035-1042
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• 2019

Background: Herbal medication is widely used in the Korean Medicine Hospital, and drug-induced liver injury (DILI) in Korea has increased proportionally. Herb-induced liver injury now accounts for approximately 40% of cases of hepatotoxicity in Korea, according to research data. Currently, however, the component responsible for the toxicity is usually unknown or can only be suspected. Objective: To study the hepatotoxicity of Cheongsimyeonja-tang in DILI. Methods: A retrospective review was conducted of 82 inpatients between April 2010 and March 2017 with suspected drug-induced liver injury (n=5). The standard criteria (RUCAM scale) for drug-induced liver injury (DILI) were applied. The electronic medical records (EMRs) were retrospectively reviewed to identify the relevant database. Aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (T. Bili) were analyzed in blood samples before and after the administration of Cheongsimyeonja-tang. Results: Five cases out of 82 patients had a criterion-referenced probable (RUCAM) score ranging from 6 to 8 points DILI. However, statistical analysis of the liver function parameters results of the 82 patients did not show a statistically meaningful elevation after taking Cheongsimyeonja-tang. Conclusions: These data suggest a relationship between Cheongsimyeonja-tang and DILI. More studies are needed to validate these observations and to explore their implications.

• Toxicological Research
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• 제24권3호
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• pp.201-206
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• 2008

Exposure to formaldehyde(FA) is closely associated with adverse health effects such as irritation, inflammation, and squamous cell carcinomas of the nasal cavities. Owing to its rapid metabolism and elimination, exposure to FA does not always result in an increased concentration in blood or urine of animals and humans. Therefore, the development of biomarkers for FA exposure is necessary for risk assessment. In the present study, the effects of FA were investigated on the expression of genes involved in the MAPK pathway in vitro and results confirmed in rats exposed to FA by inhalation. Treatment of Hs 680.Tr human tracheal epithelial cells with FA induced gene expression for PDGFA, TNFSF11, SHC1, and HRAS. HRAS expression was also increased in tracheas of rats exposed to FA. In addition, FA exposure induced the expression of RASSF4, a member of the Rasassociation domain family of Ras effectors, in rat tracheas. In conclusion, data showed FA-inducible expression of genes involved in the MAPK pathway occurred and increased expression of HRAS and RASSF4 was noted in rat tracheas subchronically exposed to FA by inhalation. These genes may serve as molecular targets of FA toxicity facilitating the understanding of the toxic mechanism.

• 한국환경보건학회지
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• 제32권5호
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• pp.440-445
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• 2006

통증경감을 위하여 광범위하게 사용되는 acetoaminophen은 치통, 두통에 주로 사용되는 의약물질이다. 의약품의 환경오염과 관련하여 수자원에 유입되는 acetaminophen의 경안천 오염정도를 파악하고 생태 위해성을 평가하기 위하여 본 연구를 수행하였다. 한강 수계이며 용인시와 광주시를 거쳐 팔당호로 흘러 들어가는 경안천(해실교, 수포교, 왕산교, 경안교, 지월교, 광동교, 팔당호)내 acetaminophen 잔류 농도와 분포를 조사하였다. 또한 Daphnia magna를 대상으로 48시간 급성독성평가를 실시하여 위해도를 평가하였다. 잔류의약품 검출을 위해 SPE 추출법을 선택 하였으며, liquid chromatography/mass spectrometry (LC/MS)를 이용하여 분석하였다. 경안천 내에서 acetaminophen 0.439 mg/l이 검출되었다. 독성평가를 실시한 결과, 48시간 $LC_{50}$은 16.9 mg/l로 나타났다. 경안천의 acetamionophen 농도와 독성평가를 바탕으로 위해성 평가를 실시한 결과 위해성은 1 이하였다 하지만 국내에 의약품 발달과 함께 사용이 계속적으로 늘어나는 추세이고, 잔류의약품에 대한 대책이 마련되어있지 않은 이상 수환경은 의약품에 노출될 것이다. 그러므로 잔류의약품이 생태계에 악영향을 미치지 않도록 구체적인 방안이 강구되어야 할 것으로 사료된다.

• Asian-Australasian Journal of Animal Sciences
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• 제29권1호
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• pp.16-22
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• 2016

The intestinal environment plays a critical role in maintaining swine health. Many factors such as diet, microbiota, and host intestinal immune response influence the intestinal environment. Intestinal alkaline phosphatase (IAP) is an important apical brush border enzyme that is influenced by these factors. IAP dephosphorylates bacterial lipopolysaccharides (LPS), unmethylated cytosine-guanosine dinucleotides, and flagellin, reducing bacterial toxicity and consequently regulating toll-like receptors (TLRs) activation and inflammation. It also desphosphorylates extracellular nucleotides such as uridine diphosphate and adenosine triphosphate, consequently reducing inflammation, modulating, and preserving the homeostasis of the intestinal microbiota. The apical localization of IAP on the epithelial surface reveals its role on LPS (from luminal bacteria) detoxification. As the expression of IAP is reported to be downregulated in piglets at weaning, LPS from commensal and pathogenic gram-negative bacteria could increase inflammatory processes by TLR-4 activation, increasing diarrhea events during this phase. Although some studies had reported potential IAP roles to promote gut health, investigations about exogenous IAP effects or feed additives modulating IAP expression and activity yet are necessary. However, we discussed in this paper that the critical assessment reported can suggest that exogenous IAP or feed additives that could increase its expression could show beneficial effects to reduce diarrhea events during the post weaning phase. Therefore, the main goals of this review are to discuss IAP's role in intestinal inflammatory processes and present feed additives used as growth promoters that may modulate IAP expression and activity to promote gut health in piglets.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.915-921
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• 2015

Context: In the last half century, discovering, developing and introducing of clinical agents from marine sources have seen great successes, with examples including the anti-cancer compound trabectedin. However, with increasing need for new anticancer drugs, further exploration for novel compounds from marine organism sources is strongly justified. Objective: The major aim of this study was to evaluate the antitumor and antioxidant potential of Sargassum tenerrimum J.Agardh (Sargassaceae) on Ehrlich ascites carcinoma (EAC) in Swiss albino mice. Materials and Methods: An ethanol extract of S. tenerrimum (EEST) from whole algae was used to evaluate cytotoxicity followed by in vivo assessment of toxicity, using biochemical parameters including hepatic and non-hepatic enzymes. Antioxidant properties were examined in animals bearing EAC treated with daily oral administration of 100-300 mg/kg extract suspension. Results: Antitumor effects of EEST in EAC bearing mice was observed with LD50 1815 mg/kg. Parameters like body weight, tumor volume, packed cell volume, tumor cell count, mean survival time and increase in life span in animals in the EAC bearing animals treated with EEST 300 mg/kg was comparable with control group. Significant differences were also seen with changes in total protein content, hepatic enzymes contents, MDA level, and free radical scavenging enzymes in untreated vs. EEST treated group animals. Conclusions: Evaluation of antioxidant enzymes and hepatic enzymes in the EAC animal model treated with EEST exhibited similar effects as the positive control drug 5-flurouracil. S. tenerrimum extracts contain effective antioxidants with significant antitumor activity.

• Journal of Korean Neurosurgical Society
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• 제52권6호
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• pp.517-522
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• 2012

Objective : Meningiomas represent 18-20% of all intracranial tumors and have a 20-50% 10-year recurrence rate, despite aggressive surgery and irradiation. Hydroxyurea, an inhibitor of ribonucleotide reductase, is known to inhibit meningioma cells by induction of apoptosis. We report the long-term follow-up result of hydroxyurea therapy in the patients with recurrent meningiomas. Methods : Thirteen patients with recurrent WHO grade I or II meningioma were treated with hydroxyurea (1000 $mg/m^2/day$ orally divided twice per day) from June 1998 to February 2012. Nine female and 4 male, ranging in age from 32 to 83 years (median age 61.7 years), were included. Follow-up assessment included physical examination, computed tomography, and magnetic resonance imaging (MRI). Standard neuro-oncological response criteria (Macdonald criteria) were used to evaluate the follow-up MRI scans. The treatment was continued until there was objective disease progression or onset of unmanageable toxicity. Results : Ten of the 13 patients (76.9%) showed stable disease after treatment, with time to progression ranging from 8 to 128 months (median 72.4 months; 6 patients still accruing time). However, there was no complete response or partial response in any patients. Three patients had progressive disease after 88, 89, 36 months, respectively. There was no severe (Grade III-IV) blood systemic disorders and no episodes of non-hematological side effects. Conclusion : This study showed that hydroxyurea is a modestly active agent against recurrent meningiomas and can induce long-term stabilization of disease in some patients. We think that hydroxyurea treatment is well tolerated and convenient, and could be considered as an alternative treatment option in patients with recurrent meningiomas prior to reoperation or radiotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.877-883
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• 2013

Background and Objective: There has been no universally agreed standard chemotherapy regimen for patients with advanced biliary tract carcinomas (BTC). We aimed to fully display and evaluate the clinical evidence for gemcitabine or gemcitabine-cisplatin combination for advanced BTC. Methods: Systematic searches were performed to identify relevant randomized controlled trials (RCTs) and uncontrolled trials. Overall survival (OS), progression-free survival (PFS), overall response rates (ORR), tumor control rates (TCR), and toxicity were evaluated. Evidence levels of the results were evaluated with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Results of the eleven gemcitabine-cisplatin trials and ten gemcitabine trials showed both chemotherapy regimens had benefits with reference to mean OS (8.63 vs. 8.79 months), mean PFS (4.86 vs. 4.72 months), pooled ORR (25.3% vs. 19.6%) and TCR (55.2% vs. 53.1%). Two RCTs showed the gemcitabine-cisplatin combination to prolong the mean PFS (mean difference [MD] 2.57, 95%CI 1.69 3.45), substantially increasing the mean OS (MD 3.59, 95% CI 3.48 3.71), and producing a similar effect in ORR (risk ratio [RR] 1.59, 95%CI 1.04 2.43), increasing TCR (RR 1.15, 95%CI 1.02 1.31) compared with gemcitabine alone, with generally manageable grade 3 or 4 adverse events. The evidence level of OS was moderate, and other outcomes (ORR, PFS, TCR, anaemia, neutropenia) were at low evidence levels. Conclusion: Available evidence was limited with low quality, which showed that both gemcitabine-cisplatin and gemcitabine alone had clinical activity with acceptable safety profiles, and gemcitabine-cisplatin appeared to be more useful for advanced BTC patients than gemcitabine alone.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 추계국제학술대회
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• pp.91-93
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• 2003

It has been estimated that the equivalent of approximately $US 50 billion has been spent on research on the behavior and fate of pesticides in the environment since Rachel Carson published “Silent Spring” in 1962. Much of the resulting knowledge has been summarized explicitly in computer algorithms in a variety of empirical, deterministic, and probabilistic simulation models. These models describe and predict the transport, degradation and resultant concentrations of pesticides in various compartments of the environment during and after application. In many cases the known errors of model predictions are large. For this reason they are typically designed to be “conservative”, i.e., err on the side of over-prediction of concentrations in order to err on the side of safety. These predictions are then compared with toxicity data, from tests of the pesticide on a series of standard representative biota, including terrestrial and aquatic indicator species and higher animals (e.g., wildlife and humans). The models' predictions are good enough in some cases to provide screening of those compounds which are very unlikely to do harm, and to indicate those compounds which must be investigated further. If further investigation is indicated a more detailed (and therefore more complicated) model may be employed to give a better estimate, or field experiments may be required. A model may be used to explore “what if” questions leading to possible alternative pesticide usage patterns which give lower potential environmental concentrations and allowable exposures. We are currently at a maturing stage in this research where the knowledge base of pesticide behavior in the environmental is growing more slowly than in the past. However, innovative uses are being made of the explosion in available computer technology to use models to take ever more advantage of the knowledge we have. In this presentation, current developments in the state of the art as practiced in North America and Europe will be presented. Specifically, we will look at the efforts of the ‘Focus’ consortium in the European Union, and the ‘EMWG’ consortium in North America. These groups have been innovative in developing a process and mechanisms for discussion amongst academic, agriculture, industry and regulatory scientists, for consensus adoption of research advances into risk management methodology.