• Toxicological Research
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• 제24권4호
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• pp.273-280
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• 2008

The single intratracheal instillation (ITI) of bleomycin (BLM) is a widely used method for inducing experimental pulmonary fibrosis in rat model. In the present study, pulmonary function tests (PFTs) of tidal volume ($V_T$), minute volume ($V_M$), and respiratory frequency ($F_R$) have been applied to study their possibility as a tool to monitor the progress of BLM-induced lung injury in rat model. Rats were treated with a single ITI of BLM (2.5 mg/kg) or saline (control). Animals were euthanized at 3, 7, 14, 21, and 28 days post-ITI. Lung toxicity effects were evaluated by inflammatory cell count, lactate dehydrogenase (LDH) activity in the bronchoalveolar lavage fluid (BALF), and light microscopic examination of lung injury. The PFT parameters were measured immediately before the animals were sacrificed. BLM treatment induced significant cellular changes in BALF-increase in number of total cells, neutrophils, and lymphocytes along with sustained increase in number of macrophages compared to the controls at days 3, 7, and 14. BALF LDH level was significantly increased compared to that in the controls up to day 14. On day 3, infiltration of neutrophils was observed in the alveolar spaces. These changes developed into marked peribronchiolar and interstitial infiltration by inflammatory cells, and extensive thickening of the interalveolar septa on day 7. At 14, 21, and 28 days, mild peribronchiolar fibrosis was observed along with inflammatory cell infiltration. The results of PFT show significant consistencies compared to the results of other toxicity tests. These data demonstrate that the most suitable time point for assessing lung fibrosis in this model is 14 days post-ITI of BLM based on the observation of fibrosis at 14, 21, and 28 days. Further, the progress of lung injury can be traced by monitoring the PFT parameters of $F_R$, $V_T$, and $V_M$.

• Molecular & Cellular Toxicology
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• 제3권4호
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• pp.238-245
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• 2007

Chronic formaldehyde inhalation studies have suggested its relativity to teratogenicity, cancer incidence, neurodegenerative and vascular disorders. Many toxicological data on the formaldehyde toxicity are available, but proteomic results showing complete protein profiles are limited. Therefore, alterations of protein expression patterns upon formaldehyde treatment were investigated in the human lung epithelial cell line. Differentially expressed proteins following formaldehyde treatment were analyzed on 2-dimensional gels, and further analyzed by MALDI-TOF to identify the proteins. Among the identified proteins, 24 proteins were notably up-regulated and 6 proteins were down-regulated. In particular, cytoskeleton related protein named vinculin and Rho GDP dissociation inhibitor which plays a key role in apoptosis increased remarkably.

• 한국임상수의학회지
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• 제16권1호
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• pp.13-18
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• 1999

This study was undertaken to find out the effect of dropwort on histopathological changes of cadmium toxicity in mice. Thirty two mice of BALB/c strain were divided into a control group (A) and three experimental groups (B, C, D). Each group was consisted of four males and four females : group A received tap water and basal diet, group B received tap water and diet supplemented with 100 mg/kg of cadmium, group C received dropwort juice and diet supplemented with 100 mg/kg of cadmium, group D received dropwort juice and basal diet. All mice were dissected on the 35th day. Pathological changes in liver, kidney, spleen, heart, lung, stomach and muscle were observed. Group D showed no significant change as the control group. But group B showed many cytoplasmic vacuoles and necrosis of hepatocytes, glomerular swelling, and degeneration and necrosis of convoluted tubules in kidney, marked congestion and hemorrhage, and a large number of variably sized alveolar macrophages appearance in lung and swelling in some part of muscle fiber. On the other hand, group C showed a little convalescent changes and maintained their normal architectures in liver, kidney, lung and muscle.

• Environmental Analysis Health and Toxicology
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• 제23권1호
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• pp.63-65
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• 2008

The tissue distribution of $TiO_2$, nanopaprticles was investigated in mice after oral administration, and skin treatment. Male mice were treated with the dose of 5 g/kg of $TiO_2$ for three consecutive days and sacrificed at 24 hours after the last administration. As results, the orally administered $TiO_2$ nanoparticels were shown to be distributed in the testis, lung, and brain at 24 hours after the last treatment. Kidney does not seem to be the main target of $TiO_2$ nanoparticle distribution. It means that $TiO_2$ nanoparticles (17 nm) are easily absorbed through entero-gastric system and may cause toxicity in brain, lung, and reproductive organs. The distribution of skin treatment showed the same pattern like oral administration.

• Journal of Chest Surgery
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• 제33권9호
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• pp.773-776
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• 2000

Accidental or suicidal fatalities of paraquat(Gramoxon) poisong are occasionally seen in the emergency room or intensive care unit in this country. In most cases, respiratory symptoms and eventual death by respiratory distress occur within several days. The most striking pathologic change is fibrosis of the lung due to widespread proliferation of fibroblastic cell. We experience a 21-year-old woman with huge bulla on left lung and diffuse fibrosis in other site, who ingested paraquat 10 months ago. After thoracoscopic removal of bulla, the patient survive without progression of pulmonary complication till now.

• Tuberculosis and Respiratory Diseases
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• 제75권5호
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• pp.181-187
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• 2013

The emergence of new therapeutic agents for non-small cell lung cancer (NSCLC) implies that histologic subtyping and molecular predictive testing are now essential for therapeutic decisions. Histologic subtype predicts the efficacy and toxicity of some treatment agents, as do genetic alterations, which can be important predictive factors in treatment selection. Molecular markers, such as epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement, are the best predictors of response to specific tyrosine kinase inhibitor treatment agents. As the majority of patients with NSCLC present with unresectable disease, it is therefore crucial to optimize the use of tissue samples for diagnostic and predictive examinations, particularly for small biopsy and cytology specimens. Therefore, each institution needs to develop a diagnostic approach requiring close communication between the pulmonologist, radiologist, pathologist, and oncologist in order to preserve sufficient biopsy materials for molecular analysis as well as to ensure rapid diagnosis. Currently, personalized medicine in NSCLC is based on the histologic subtype and molecular status. This review summarizes strategies for tissue acquisition, histologic subtyping and molecular analysis for predictive testing in NSCLC.

• Journal of Yeungnam Medical Science
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• 제38권4호
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• pp.366-370
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• 2021

Immune checkpoint inhibitors (ICIs) have become the main drugs for programmed cell death receptor-1 or ligand-1 expressing non-small cell lung cancer (NSCLC) combined with conventional chemotherapy. ICIs are generally more tolerable than cytotoxic chemotherapies in terms of toxicity, and ICI-related adverse events are mild and manageable. However, these drugs may lead to unexpected severe adverse events such as immune-related hematologic toxicities, which could be life-threatening. Here, a rare case of a pembrolizumab-related adverse event in a patient with NSCLC who showed early-onset hemolytic anemia and recovered by high-dose steroid and a series of plasma exchanges is reported.

• 한국응용과학기술학회지
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• 제29권1호
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• pp.129-140
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• 2012

우리나라에서 건축물 내장재의 화재안전성능은 국토해양부 고시 제2011-39호에 의한 평가방법에 의해 불연성시험(KS F ISO 1182), 열방출률시험(KS F ISO 5660) 및 가스유해성시험(KSF 2271)을 실시하여 그 결과로서 분류하도록 되어 있다. 그 중 연기 및 연소독성가스에 대한 시험인 가스 유해성 시험은, 건축재료 및 내장재의 연소시 발생하는 가스의 유해성을 마우스의 평균 행동정지시간으로 측정하는 방법으로 사용하여 왔다. 이 중 연소 독성가스 4종(HCl, HF, HCN, $SO_2$) 흡입독성시험방법의 확립을 위하여 ICR계 mouse와 전신흡입노출장치를 이용하여, 독성가스 노출 및 병리검사를 수행하였다. 그 결과 호흡기관지와 가까운 폐포에서 대식세포(Macrophage)의 침윤을 유발하는 것으로 나타났고, 4종의 물질에 대한 조직의 병리검사로 전체적으로 충혈과 울혈은 확인되었다. 조직 중 폐와 신장에서 조직손상이 심하였고, 물질로는 HCN이 가장 많은 병리소견을 보였다.

• Toxicological Research
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• 제31권2호
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• pp.203-211
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• 2015

Trichloroacetonitrile is used as an intermediate in insecticides, pesticides, and dyes. In Korea alone, over 10 tons are used annually. Its oral and dermal toxicity is classified as category 3 according to the globally harmonized system of classification and labelling of chemicals, and it is designated a toxic substance by the Ministry of Environment in Korea. There are no available inhalation toxicity data on trichloroacetonitrile. Thus, the present study performed inhalation tests to provide data for hazard and risk assessments. Sprague-Dawley rats were exposed to trichloroacetonitrile at concentrations of 4, 16, or 64 ppm for 6 hour per day 5 days per week for 13 weeks in a repeated study. As a result, salivation, shortness of breath, and wheezing were observed, and their body weights decreased significantly (p < 0.05) in the 16 and 64 ppm groups. All the rats in 64 ppm group were dead or moribund within 4 weeks of the exposure. Some significant changes were observed in blood hematology and serum biochemistry (e.g., prothrombin time, ratio of albumin and globulin, blood urea nitrogen, and triglycerides), but the values were within normal physiological ranges. The major target organs of trichloroacetonitrile were the nasal cavity, trachea, and lungs. The rats exposed to 16 ppm showed moderate histopathological changes in the transitional epithelium and olfactory epithelium of the nasal cavity. Nasal-associated lymphoid tissue (NALT) and respiratory epithelium were also changed. Respiratory lesions were common in the dead rats that had been exposed to the 64 ppm concentration. The dead animals also showed loss of cilia in the trachea, pneumonitis in the lung, and epithelial hyperplasia in the bronchi and bronchioles. In conclusion, the no-observed-adverse-effect level (NOAEL) was estimated to be 4 ppm. The main target organs of trichloroacetonitrile were the nasal cavity, trachea, and lungs.

• Toxicological Research
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• 제14권3호
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• pp.401-409
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• 1998

Group of 40 male and 40 female ICR mice was given daily per oral treatment with the combination of enalapril plus Ginkgo biloba extract (EGb 761), 3+9mg/kg/day(low dosage group), 10+30mg/kg/day (middle dosage group), 30+90mg/kg/day (high dosage group) for 3 months in drinking water according to Established Regulation of Korean National Institute of Safety Research (1994. 4.14). Appearance, behavior, mortality, and food consumption of mouse of treated groups were not affected during the experimental periods. No significant the combination of enalapril plus Ginkgo biloba extract (EGb 761)-related changes were found in urinalysis, hematology, serum chemistry, and organ weight, Lung edema were observed and the weight of lung were increased in low dosage treated group of the male mice, which be associated with enalapril treatment, but these changes were not found in middle and high dosage group. Our results suggest that to toxic changes were found in rat treated orally with the combination of enalapril plus Ginko biloba extract (EGb 761) for 3 months.