• 대한한방내과학회지
• /
• 제32권2호
• /
• pp.217-231
• /
• 2011

Objectives : This study aimed to evaluate the effects of Saengmaekcheongpye-eum (SCE) on a LPS-induced COPD (chronic obstructive pulmonary disease) model. Materials and Methods : The extract of SCE was treated to A549 cells and and LPS-induced COPD mouse model. Then, various parameters such as cell-based cyto-protective activity and histopathological finding were analyzed. Results : SCE showed a protective effect on LPS-induced cytotoxicity in A549 cells. This effect was correlated with analysis for caspase 3 levels, elastin contents, protein levels of cyclin B1, Cdc2, and phospho-Erk1/2, and gene expression of TNF-${\alpha}$ and IL-$1{\beta}$ in A549 cells. SCE treatment also revealed a protective effect on LPS-induced lung injury in COPD mouse model. This effect was evidenced via histopathological findings including immunofluorescence stains against elastin and caspase 3, and protein levels of cyclin B1, Cdc2, and Erk1/2 in lung tissue. Conclusions : These data suggest that SCE has pharmaceutical properties on lung injury. This study thus provides scientific evidence for the efficacy of SCE for clinical application to patients with COPD.

• 한국한의학연구원논문집
• /
• 제5권1호
• /
• pp.1-15
• /
• 1999

Chronic asthma is considered as an incurable disease in modern society. This study focused on development of an animal model for the chronic asthma to investigate new drugs from traditional herbal medicine. And we tested the animal model with a typical prescription, Chungsangboha-tang and tried to find biochemical markers such as catecholamines and cAMP in serum, and as densities of beta-receptor in lung tissues. SD rats were actively sensitized by exposure to ovalbumine (OA). Ten days after sensitization, rats were challenged with OA aerosol by nebulizer six times every three days. Mucin was increased in bronchoalveolar lavages (BALs) after antigen (OA) challenge. Serum concentration of epinephrine was decreased significantly although there were not changed much in serum concentration of cAMP and the densities of beta-receptor in lung tissues. Chungsangboha-tang (5 g/kg/day) was given orally to ovalbumin-sensitized rats (n=8) for 15 days. Mucin in bronchoalveolar lavages (BALs) was increased significantly after treatment of Chungsangboha-tang although concentrations of epinephrine and cAMP were not changed significantly. The densities of beta-receptor in lung tissues were not different from those of controls. These results suggest that the ovalbumin-sensitized rats can be a good animal model of chronic asthma and Chungsangboha-tang is a possible drug in the treatment of chronic asthma.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권11호
• /
• pp.6899-6903
• /
• 2013

Background: Prevalence is a statistic of primary interest in public health. In the absence of good follow-up facilities, it is difficult to assess the complete prevalence of cancer for a given registry area. Objective: An attempt was here made to arrive at complete prevalence including limited duration prevalence with respect to selected sites of cancer for India by fitting appropriate models to 1, 3 and 5 years cancer survival data available for selected population-based registries. Materials and Methods: Survival data, available for the registries of Bhopal, Chennai, Karunagappally, and Mumbai was pooled to generate survival for breast, cervix, ovary, lung, stomach and mouth cancers. With the available data on survival for 1, 3 and 5 years, a model was fitted and the survival curve was extended beyond 5 years (up to 35 years) for each of the selected sites. This helped in generation of survival proportions by single year and thereby survival of cancer cases. With the help of survival proportions available year-wise and the incidence, prevalence figures were arrived for selected cancer sites and for selected periods. Results: The prevalence to incidence ratio (PI ratio) stabilized after a certain duration for all the cancer sites showing that from the knowledge of incidence, the prevalence can be calculated. The stabilized P/I ratios for the cancer sites of breast, cervix, ovary, stomach, lung, mouth and for life time was observed to be 4.90, 5.33, 2.75, 1.40, 1.37, 4.04 and 3.42 respectively. Conclusions: The validity of the model approach to calculate prevalence could be demonstrated with the help of survival data of Barshi registry for cervix cancer, available for the period 1988-2006.

• Journal of Radiation Protection and Research
• /
• 제28권1호
• /
• pp.43-50
• /
• 2003

본 연구는 호흡을 통해 우라늄을 만성 또는 급성섭취한 경우 생물분석 결과의 해석을 통해 예탁유효선량을 평가하는 실질적인 방법을 기술하고 있다. 인체에서의 우라늄 거동의 해석을 위해 인체의 장기를 ICRP에서 권고하는 소화기 모델, 호흡기 모델 그리고 생체역동학적 모델에 따라 일련의 수학적 격실로 구성하였다. Birchall의 알고리듬을 이용하여 각 격실에서의 균형방정식의 해석적인 해를 얻었으며 우라늄의 소변 배설함수와 폐 잔류함수를 획득하였다. 소변 중 우라늄 농도와 폐 계수기로 측정된 폐 부하량에 각각 배설 및 잔류함수를 적용하여 섭취모드에 따른 초기 섭취량 또는 총 섭취량을 계산하였다. 예탁유효선량은 ICRP 78에서 제공하는 선량 환산계수를 계산된 섭취량에 적용함으로써 평가된다.

• Journal of Trauma and Injury
• /
• 제21권2호
• /
• pp.120-127
• /
• 2008

Purpose: Many studies on the time course of inducible nitric oxide synthase (iNOS) gene expression have been performed in the LPS (Lipopolysaccharide)-induced endotoxemic model, but there have been few experimental approaches to continuous peritonitis-induced sepsis model. We conducted this study to establish basic data for future sepsis-related research by investigating the time course of iNOS gene expression and the relationship with the production of inflammatory mediators in the early sepsis model induced by cecal ligation and puncture (CLP). Methods: Male Sprague-Dawley rats were operated on by sing the CLP method to induce of peritonitis; and then, they were sacrificed and samples of blood and lung tissues were obtained at various times (1,2,3,6,9 and 12 h after CLP). We observed the expression of iNOS mRNA from lung tissues and measured the synthesis of nitric oxide, $IL-1{\beta}$, and $TNF-{\alpha}$ from the blood. Results: iNOS mRNA began to be expressed at 3 h and was maintained untill 12 h after CLP. The nitric oxide concentration was increased significantly at 6 h, reached its peak level at 9 h, and maintained a plateau untill 12 h after CLP. $TNF-{\alpha}$ began to be detected at 3 h, increased gradually, and decreased steeply from 9 h after CLP. $IL-1{\beta}$ showed its peak level at 6 h after CLP, and tended to decrease without significance. Conclusion: We observed that the iNOS gene was expressed later in peritonitis-induced sepsis than in LPS-induced sepsis. Nitric oxide and key inflammatory mediators were also expressed later in peritonitis-induced sepsis than in LPS-induced sepsis.

• Journal of Veterinary Science
• /
• 제22권2호
• /
• pp.20.1-20.13
• /
• 2021

Background: Pseudorabies virus (PRV) infection leads to high mortality in swine. Despite extensive efforts, effective treatments against PRV infection are limited. Furthermore, the inflammatory response induced by PRV strain GXLB-2013 is unclear. Objectives: Our study aimed to investigate the inflammatory response induced by PRV strain GXLB-2013, establish an inflammation model to elucidate the pathogenesis of PRV infection further, and develop effective drugs against PRV infection. Methods: Kunming mice were infected intramuscularly with medium, LPS, and different doses of PRV-GXLB-2013. Viral spread and histopathological damage to brain, spleen, and lung were determined at 7 days post-infection (dpi). Immune organ indices, levels of reactive oxygen species (ROS), nitric oxide (NO), and inflammatory cytokines, as well as levels of activity of COX-2 and iNOS were determined at 4, 7, and 14 dpi. Results: At 10⁵-10⁶ TCID₅₀ PRV produced obviously neurological symptoms and 100% mortality in mice. Viral antigens were detectable in kidney, heart, lung, liver, spleen, and brain. In addition, inflammatory injuries were apparent in brain, spleen, and lung of PRV-infected mice. Moreover, PRV induced increases in immune organ indices, ROS and NO levels, activity of COX-2 and iNOS, and the content of key pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, interferon-γ and MCP-1. Among the tested doses, 10² TCID₅₀ of PRV produced a significant inflammatory mediator increase. Conclusions: An inflammatory model induced by PRV infection was established in mice, and 10² TCID50 PRV was considered as the best concentration for the establishment of the model.

• 한국의학물리학회:학술대회논문집
• /
• 한국의학물리학회 2002년도 Proceedings
• /
• pp.174-176
• /
• 2002

A total of 134 patients with stage 1 of non-small cell lung cancer treated by carbon ion beam of HIMAC NIRS were investigated for control rate and delivered dose. The delivered dose of every patient was converted to biological effective dose (BED) of LQ model using fraction number, dose per fraction and alpha beta ratio which shows the maximum correlation between BED and tumor control. The BED of every patient was classified to establish a BED response curve for control. Assuming fraction numbers, dose response curves were introduced from BED response curve. The total doses to realize several control rates were obtained for the treatment of small fraction number.

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2003년도 추계학술대회
• /
• pp.163-163
• /
• 2003

Difficulties of long-tenn survival of lung cancer patients treated with conventional therapies require the need for novel approaches and gene therapy holds promise in this area. Several genes are known to have anti-tumor activities and have been used as a gene of delivery, however, a number of problems such as efficiency, specificity of the gene delivery hinder the application of gene therapy.(omitted)

• Molecules and Cells
• /
• 제43권10호
• /
• pp.889-897
• /
• 2020

K-RAS is frequently mutated in human lung adenocarcinomas (ADCs), and the p53 pathway plays a central role in cellular defense against oncogenic K-RAS mutation. However, in mouse lung cancer models, oncogenic K-Ras mutation alone can induce ADCs without p53 mutation, and loss of p53 does not have a significant impact on early K-Ras-induced lung tumorigenesis. These results raise the question of how K-Ras-activated cells evade oncogene surveillance mechanisms and develop into lung ADCs. RUNX3 plays a key role at the restriction (R)-point, which governs multiple tumor suppressor pathways including the p14^ARF-p53 pathway. In this study, we found that K-Ras activation in a very limited number of cells, alone or in combination with p53 inactivation, failed to induce any pathologic lesions for up to 1 year. By contrast, when Runx3 was inactivated and K-Ras was activated by the same targeting method, lung ADCs and other tumors were rapidly induced. In a urethane-induced mouse lung tumor model that recapitulates the features of K-RAS-driven human lung tumors, Runx3 was inactivated in both adenomas (ADs) and ADCs, whereas K-Ras was activated only in ADCs. Together, these results demonstrate that the R-point-associated oncogene surveillance mechanism is abrogated by Runx3 inactivation in AD cells and these cells cannot defend against K-Ras activation, resulting in the transition from AD to ADC. Therefore, K-Ras-activated lung epithelial cells do not evade oncogene surveillance mechanisms; instead, they are selected if they occur in AD cells in which Runx3 has been inactivated.

• Applied Microscopy
• /
• 제33권1호
• /
• pp.1-16
• /
• 2003

급성호흡곤란증후군 (acute respiratory distress syndrome)을 포함한 급성폐손상의 기전을 산화성스트레스와 연관하여 알아보기 위하여 본 연구를 시행하였다. N-nitroso-N-methylurethane (NNNMU)은 실험동물에 있어서 사람에서 보이는 ARDS와 유사한 병리학적인 소견을 보이므로 ARDS의 모델로 사용된다. 본 연구에서는 흰쥐에서 NNNMU로 급성폐손상을 유도한 뒤 이를 Lung weight/Body weight ratio, 폐포세척액(BAL)내의 단백함량을 측정하여 확인하고, 동시에 호중구의 침윤에 의한 산소기형성, 이에 따른 산화성스트레스를 확인하기 위하여 BAL 내의 호중구수의 산정 및 폐장의 MPO 활성도를 측정하였다. 동시에 광학현미경, 전자현미경 및 세포화학적 전자현미경법을 이용하여 호중구에 의한 급성폐손상, 호중구의 침윤 및 미세구조의 변화 및 산소기의 생성을 확인하였다. 대조군에 비하여 NNNMU를 투여한 흰쥐에서는 BAL 내의 단백질이 증가하고 BAL 내의 호중구의 증가, 폐장의 MPO 활성도의 증가로 호중구의 침윤이 증가함을 관찰하였다. 광학현미경상 호중구의 침윤, 폐포내 호중구의 유입 및 vascular cuffing 등이 관찰되었다. 전자현미경 소견상 제2형 폐포세포는 산화성 스트레스의 전형적 소견을 보이고 조직의 손상은 호중구에 의한 손상으로 생각되었으며 세포화학적 전자현미경법으로 산소기의 생성이 증가됨을 확인하였다. 이러한 결과들을 종합할 때 NNNMU에 의한 급성폐손상은 호중구의 산소기 생성에 의한 산화성스트레스에 의한 것으로 생각되었다.