Heparin이 망내계세포에 미치는 영향에 관한 초미형태학적 연구

이동철,김중길,임정교,손윤경,서인수,손태중 慶北大學校 醫科大學 1991 慶北醫大誌 Vol.32 No.3

저자들은 heparin 투여후 세망내피계의 초미형태학적 변화를 관찰하기 위해 Sprague-Dawley계 숫쥐에 heparin과 endotoxin을 투여한 후 비장을 채취하여 실험에 이용하였다. 실험군은 heparin 전처치군과 heparin 후처치군으로 나누었으며 비교군으로 heparin 단독투여군과 endotoxin 단독투여군을 설정하여 각각을 투약후 비장을 채취하여 광학현미경 및 전자현미경적 검색을 실시하였다. 실험결과를 요약하면 heparin 단독투여군은 대식세포, 형질세포양 림프아구 및 다핵백혈구가 증가되었고, 대식세포의 탐식능도 항진되었다. 그러나 대식세포자체의 소기관 발달은 현저하지 않았다. Endotoxin 단독투여군은 시간이 갈수록 대식세포의 탐식능이 저하되고, 파괴가 증가되어 수가 감소하였다. 미소혈전이 자주 관찰되었으며 기타세포들의 파괴가 관찰되었다. Heparin 전처치 및 후처치군은 공히 endotoxin군에 비해 대식세포 탐식능이 증가되었다. 이상의 성적으로 보아 heparin의 망내세포에 대한 영향은 주로 대식세포의 탐식능과 수의 증가로 생각되며 이는 정상 및 병적상태 모두에서 일어난다고 생각된다. 또한 ET 투여 전후 heparin을 투여한 실험군에서 공히 대식세포 탐식능이 증가되었으므로 이는 ET shock 후 조직손상으로 분비되는 세망내피계 저하물질에 대해 heparin이 길항작용을 할 것으로 생각된다. 또한 heparin의 대식세포 탐식능항진에 대한 효과는 세포의 직접적인 자극이라기 보다는 탐식과정중 특히 oposonization에 효과를 미칠 것으로 생각된다. The authors studied an ultrastructural changes of reticuloendothelial system after administration of heparin. Male Sprague-Dawley rats were examined after administration of heparin and endotoxin. The experimental groups were divided into heparin pretreated groups and heparin posttreated groups. The control groups were divided into heparin-only groups and endotoxin-only groups. Each animals were sacrificed and spleens were extirpated and examined by light and electron microscopy. The results obtained were summarized as follows: Heparin-only groups showed proliferation of macrophages, lymphocytes and neutrophils. The phagocytic activity of marcophage is enhanced. The cytoplamic organellar change is not remarkable except increase of secondary lysosomes. Endotoxin-only groups showed decrease of phagocytic cells. The phagocytic activity is also depressed. Destruction of macrophages and other cells are noted. Microthrombi are frequently seen. Both heparin pretreated and heparin posttreated groups revealed relative enhancement of phagocytic activity compaired to endotoxin-only groups. From the result of the experimental study, it appears that the effect of heparin on the reticuloendothelial system is enhancement of phagocytic activity of macrophages both in the coditions of normal and pathologic one. And it also suggests that heparin may act as an antagonizing factor to the reticuloendothelial depressing agent that may be derived from injured organ of endotoxin shock. And the effect of heparin to the phagocytic activity of macrophage may be related to the process of phagocytosis such as opsonization or to the direct cellular stimulation.

網內系 貪食能의 日週期 變動에 對한 實驗的 硏究

李東根,李惠洙,崔三任,金象皓,金興坤 전북대학교 의과학연구소 1986 全北醫大論文集 Vol.10 No.4

To investigate circadian rhythm of the phagocytic function of reticuloendothelial system in rats, the phagocytic activity was measured by means of carbon clearance method with 4-h intervals for a 24-h span. The results were as follows. The phagocytic activity increased during the habitual resting light span of nocturnally active rat, but decreased during the active dark span. There is no significant difference between the male, and female rats. (Key words : circadian rhythm, phagocytic function, Reticuloendothelial system)

Predicting the in vivo accumulation of nanoparticles in tumor based on in vitro macrophage uptake and circulation in zebrafish

Chang, H.,Yhee, J.Y.,Jang, G.H.,You, D.G.,Ryu, J.H.,Choi, Y.,Na, J.H.,Park, J.H.,Lee, K.H.,Choi, K.,Kim, K.,Kwon, I.C. Elsevier Science Publishers 2016 Journal of controlled release Vol.244 No.2

<P>Nanoparticles have resulted in great progress in biomedical imaging and targeted drug delivery in cancer theranostics. To develop nanoparticles as an effective carrier system for therapeutics, chemical structures and physicochemical properties of nanoparticle may provide a reliable means to predict the in vitro characteristics of nanoparticles. However, in vivo fates of nanoparticles, such as pharmacokinetics and tumor targeting efficiency of nanoparticles, have been difficult to predict beforehand. To predict the in vivo fates of nanoparticles in tumor-bearing mice, differences in physicochemical properties and in vitro cancer cell/macrophage uptake of 5 different nanoparticles with mean diameter of 200-250 nm were comparatively analyzed, along with their circulation in adult zebrafish. The nanoparticles which showed favorable cellular uptake by macrophages indicated high unintended liver accumulation in vivo, which is attributed to the clearance by the reticuloendothelial system (RES). In addition, blood circulation of nanoparticles was closely correlated in adult zebrafish and in mice that the zebrafish experiment may elucidate the in vivo behavior of nanoparticles in advance of the in vivo experiment using mammal animal models. This comparative study on various nanoparticles was conducted to provide the basic information on predicting the in vivo fates of nanoparticles prior to the in vivo experiments. (C) 2016 Elsevier B.V. All rights reserved.</P>

Improved tumor targeting and antitumor activity of camptothecin loaded solid lipid nanoparticles by preinjection of blank solid lipid nanoparticles

Jang, Dong-Jin,Moon, Cheol,Oh, Euichaul Elsevier 2016 BIOMEDICINE AND PHARMACOTHERAPY Vol.80 No.-

<P><B>Abstract</B></P> <P>This study aimed to enhance the in vivo antitumor effects of camptothecin (CPT), a strong antitumor agent whose delivery is limited by poor aqueous solubility and instability of the active lactone form. CPT was loaded into sterically stabilized, solid lipid nanoparticles (CPT-SLNs) formulated for intravenous administration. The influence of preinjected blank SLNs on the tumor targeting, pharmacokinetics and antitumor activity of CPT-SLNs was investigated. The CPT-SLNs composed of trilaurin-based lipid matrix containing poloxamer188 and pegylated phospholipid as stabilizers were prepared by hot homogenization method and evaluated for in vitro characteristics and in vivo performance. The CPT-SLNs showed an in vitro long-term sustained release pattern and effectively protected the CPT lactone form from hydrolysis under physiological conditions. Notable tumor targeting and tumor growth inhibition were observed after intravenous administration of CPT-SLNs to mice with subcutaneous transplants of CT26 carcinoma cells. In pharmacokinetic studies in rats, CPT-SLNs markedly elevated plasma CPT level and prolonged blood circulation compared to free CPT. Nonetheless, high uptake of CPT-SLNs by reticuloendothelial system (RES)-rich tissues resulted in limited tumor targeting of CPT-SLNs and plasma CPT levels. Preinjection of blank SLNs before administration of CPT-SLNs to tumor-bearing mice substantially reduced the accumulation of CPT-SLNs in RES organs. This led to significantly enhanced tumor targeting, improved pharmacokinetic parameters and increased antitumor efficacy of CPT-SLNs. These results suggested that the in vivo antitumor effects of CPT-SLNs could be further enhanced by preinjection of blank SLNs. Therefore, CPT-SLNs with preinjected blank SLNs could be a potential approach for stable and effective CPT-based cancer therapy.</P>

말라리아 환자의 간스캔에서 폐섭취군과 비섭취군의 혈액생화학적 지표 및 임상양상의 비교

안석진 ( Seok Jin Ahn ),박상준 ( Sang Jun Park ),김윤권 ( Yun Kwon Kim ),김영중 ( Young Jung Kim ),김소연 ( So Yon Kim ),조민구 ( Min Gu Cho ),양병윤 ( Byeong Yun Yang ),김종수 ( Jong Soo Kim ),정재혁 ( Jae Hyuk Jung ),김지훈 ( Ji 대한내과학회 2007 대한내과학회지 Vol.73 No.2

목적: 간스캔시 나타나는 폐섭취는 여러 질환과 관련이 있으며, 특히 감염질환에서 일시적으로 보일 수 있는 현상으로 보고되는 경우가 많았다. 말라리아 환자들에서 간스캔상 미만성 폐섭취 현상에 대한 보고가 있는바, 저자들은 말라리아로 입원한 환자들에게 간스캔을 시행하여 그들의 임상양상과 혈액검사상의 이상이 폐섭취와 어떤 상관관계가 있는지 고찰해 보았다. 방법: 1999에서 2004년까지 말라리아로 내원한 환자 중 간스캔을 시행한 환자 20명을 대상으로 하였다. 간스캔 결과 폐섭취된 환자들과 섭취가 되지 않은 환자들을 나누어 간스캔 당시의 혈액 검사 소견과 호흡기 증상을 포함한 임상양상지표를 비교 분석하였다. 결과: 말라리아 환자에서 간스캔상 폐섭취 현상은 대상의 반수에서 나타났다. 섭취군과 비섭취군으로 나누어 비교했을 때, 혈소판수는 각각 평균 74,000/mm3, 165,000/mm3 (p=0.012), 그리고 총콜레스테롤은 각각 평균 80.3 mg/dL, 105.7 mg/dL 보였으며(p=0.033), 간스캔상 골수 섭취는 비폐섭취군에 비해 증가하였으며(p=0.008) 이들 모두 통계적으로 유의하였지만, 총 발열기간 등을 포함하여 다른 지표들은 유의한 상관관계가 없었다. 결론: 말라리아 환자의 50%에서 간스캔상 폐섭취 증가를 보이고 있어 이는 말라리아의 특징적인 소견으로 보이며, 간스캔상 폐섭취가 있었던 군이 폐섭취가 없었던 군에 비하여 골수 섭취가 증가하는 양상으로 나타나, 폐섭취군에서 말라리아로 인한 과도한 세망내피계 활성이 일어남과 동시에 혈소판수와 콜레스테롤의 현저한 감소와 동반됨을 발견하였다. Background: Lung uptake during liver scanning has been considered as a passing phenomenon related to several diseases, and especially infectious diseases and malignancy. Some reports have shown diffuse lung uptake during liver scanning of malarial patients. Therefore, we tried to determine the relationship between the abnormalities of the clinical features, including the hematobiochemical indices and the lung uptake during liver scanning, by analyzing the information of the malarial patients. Methods: We performed 99mTechnethium(Tc)-sulfur colloid liver scanning on 20 of the 45 malarial patients who were admitted from 1999 to 2004. We divided them into two groups, the Lung-Uptake (LU) group and the Non-Lung-Uptake (NLU) group. We analyzed the hematobiochemical indices and clinical features, including the respiratory symptoms, between the two groups. Results: 10 of the 20 malarial patients showed lung uptake on the liver scan. The mean platelet counts were 74,000/L and 165,000/L, respectively, in the LU group and the NLU group (p=0.012). Also, the mean total cholesterol levels were 80.3 mg/dL and 105.7 mg/dL, respectively, in the LU group and the NLU group (p=0.033). The scores of the bone marrow (BM) uptake in the LU group were higher than those in the NLU group (p=0.008). Yet the other values such as Hb, ALT, albumin and total bilirubin were not statistically significant, nor were the peak body temperatureand other features. Conclusions: Half of the patients had lung uptake on the liver scanning, and this may be considered as a characteristic of vivax malaria. The BM uptake during liver scanning in the LU group was more increased, and this is supposed to be a consequence of hyperstimulated reticuloendothelial system, which was accompanied by thrombocytopenia and a lower level of total cholesterol in malarial patients.(Korean J Med 73:183-191, 2007)

Lentinus edodes IY105 알칼리 추출물의 보체계활성 및 항종양효과

이준우,정천희,정훈,이권행 한국산업미생물학회 1990 한국미생물·생명공학회지 Vol.18 No.6

경기도 광릉에서 채집한 자실체로부터 분리한 Lentinus edodes IY105균을 배양하여 얻은 균사체를 알칼리로 추출하여 얻은 물질이 면역계와 sarcoma 180이 이식된 mouse에 미치는 영향을 검토하였다. Lentinus edodes IY105 배양균사체의 알칼리 추출물은 항보체활성과 alternative complement hemolytic 활성을 가지고 있었고, carbon clearance 활성을 나타내는 것으로 보아 mouse의 망내계에 존재하는 macrophage를 활성화시켜 이물질에 대한 탐식기능을 증가시킴을 알 수 있었다. 또한, 이물질은 mouse의 용혈반 형성 세포수를 증가시키는 것으로 보아 항체생산 자극효과가 있는 것으로 추측되었으며, 종양세포인 sarcoma 180이 이식된 mouse의 암을 50% 정도 억제하는 효과를 나타내었다. 알칼리 추출물의 성분을 분석한 결과, 당 17%, 단백질 42%로 구성된 단백다당체가 주성분으로 단백다당체는 16종의 아미노산과 5종류의 당으로 구성되어 있었다. Alkali extract obtained from mycelia of Lentinus edodes IY105 was shown to have potent anticomplementary activity and alternative complementary activity in vitro. It was also shown to activate reticuloendothelial system of ICR mice in the carbon clearance. Amount of carbohydrates and protein of the extract were 17% and 42% respectively. It was found that carbohydrates were consisted of 5 monosaccharides and protein was consisted of 16 amino acids. Antitumor activity was observed in the alkali extract treated group of sarcoma 180 bearing ICR mice.