• 공업화학
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• 제22권6호
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• pp.599-604
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• 2011

이 연구는 화상이 유발된 mouse에 사이클로덱스트린/폴리에틸렌이민/실크 피브로인이 함유된 수화겔을 처치하여 화상 치유효능을 평가한 실험이다. 상처치유 효능을 갖는 것으로 알려진 silk fibroin (SF)을 함유한 polyethyleneimine (PEI)/${\beta}$-cyclodextrin (${\beta}CD$) conjugate를 epichlorohydrin (EPI)로 가교시켜 ${\beta}CD/PEI/SF$ 수화겔을 제조하였고, 이를 화상이 유발된 mouse에 처치하여 일반 거즈만 처치한 음성대조군과 상용화되어 있는 상처치유 제품(OTC)을 처치한 양성대조군과 비교해 시간에 따른 화상치유 경과를 지켜보았다. 약물이 로딩되지 않은 ${\beta}CD/PEI/SF$ 수화겔과 약물이 로딩된 ${\beta}CD/PEI/SF$ 수화겔을 처치한 동물 실험군의 화상치유경과는 육안으로 관찰 시, 음성대조군과 비교했을 때에 큰 차이가 없었고 오히려 상처가 악화되는 경향을 보였다. 반면 OTC 연고를 처치한 양성대조군에서는 상처의 크기가 눈에 띄게 줄어들었다. H&E staining을 통하여 진피 층에서의 상피재생을 확인한 결과 또한 ${\beta}CD/PEI/SF$ 수화겔의 화상치유에 대한 효능이 뚜렷하게 나타나지 않았다.

• Journal of Korean Neurosurgical Society
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• 제29권10호
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• pp.1289-1295
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• 2000

Purpose : Recent evidence suggests a possible role for leukocytes in brain injury following ischemia and reperfusion. This study examined the temporal profile of ischemic tissue damage and leukocyte response after transient middle cerebral artery occlusion(MCAO) with reperfusion in the mouse. Methods : Focal cerebral ischemia was made by temporary occluding of the stem of the proximal MCA. Two groups of the mouse were investigated : (1) sham operation(n＝10), and (2)those having the arterial occlusion released after 90 minute(n＝20). By 4 hours(n＝10) and 24 hours(n＝10) after the onset of ischemia-reperfusion, fluorescein videoimages were under-taken in the pial venules of the mouse using a closed cranial window technique. Rhodamine 6G was administered as a $80-100{\mu}l/min$ i.v. loading dose and a $30-40{\mu}l/min$ i.v. maintenance dose in saline to selectively label circulating leukocytes. Neuropathologic evaluation for brain injury was accomplished using the histochemical stain 2,3,5-triphen-yltetrazolium chloride(TTC) and hematoxylin and eosin(H & E) stain. Results : The mean number of adherent leukocytes to cerebral venules in the 90 minutes MCAO and 24 hours reperfusion group were $306{\pm}24$ compared with $72{\pm}8$ in the sham operation group. In the TTC staining method, the cortical infarct affecting 34.8% of hemispheric volume were created in all of animals (n＝10) undergoing 90 minute MCAO with 24 hours reperfusion, but the infarcted area were not found in the other(sham operation and 90 minute MCAO with 4 hours reperfusion)groups. In the H & E stain, the brain tissue following 90 minute MCAO with 4 hours reperfusion revealed only a pyknosis of the nuclei with shrunken cytoplasm, but infiltrated leukocytes were not observed. After 24 hours of reperfusion, a many leukocytes were infiltrated within parenchyma and blood vessles. Conclusions : These findings demonstrate the feasiblity of continous in vivo monitoring of leukocyte adherence in cerebral venules and suggest that reperfusion induced leukocyte adherence to venular endothelium may contribute to tissue injury following focal cerebral ischemia.

• 동의생리병리학회지
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• 제21권6호
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• pp.1549-1554
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• 2007

To verify the effects of JAUN-1, which is a water-extracted herbal mixture, on gastroenteric disorders induced by 0.1 percent of iodoacetamide (IA) in rats. We divided four groups, $Na{\"{\i}}ve$ + Distilled Water (DW), 0.1% IA + DW, 0.1% IA + Proton pump inhibitor (Lansoprazole, 5 mg/kg) and 0.1% IA + Herbal mixture (JAUN-1, 50mg/kg) and performed following experimental methods to confirm its advantageous effects against ulcerogenic stomach in rats induced by 0.1% IA; cell cytotoxicity, analysis of lesions score, Hematoxylin & Eosin (H&E) stain, RT-PCR for ${\beta}-actin$, COX-1 and COX-2 and evaluation of intestinal prokinetic activity. No cytotoxicity was elucidated at the concentration of 1, 5, 10, 50, 100, $500\;{\mu}g/ml$ and 1mg/ml JAUN-1 through MTT Assay using by human stomach epithelial AGS cells, respectively. In addition, the JAUN-1 treated group and the lansoprazole treated group significantly decreased in lesions score compared to the DW treated group in the gastritis induced rat model, and results of immunohistochemistry by H&E staining showed that histological recovery in Proton Pump Inhibitor (PPI) and JAUN-1 treated groups rather than the DW administrated group. Another outcome was that ${\beta}-actin$ relative COX-2 expression level was significantly promoted in the DW treated group while ${\beta}-actin$ relative COX-1 expression level was no meaningful change in this rat model. Finally, intestinal prokinetic activity was recovered from low level of prokinetic activity due to 0.1% IA induced gastritis to the similar level of Normal group. These results suggested that JAUN-1 may have beneficial effects against 0.1% IA-induced gastritis rat model through decreasing lesions score, histological recovery, ${\beta}-actin$ relative COX-1, 2 expression level and prokinetic activity.

• 대한임상검사과학회지
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• 제54권1호
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• pp.9-14
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• 2022

궤양성 대장염은 면역학적인 이상과 유전적인 요소에 의해 대장의 점막 또는 점막밑층에 염증을 유발하는 질환이다. 이전 연구에 의하면, 비만은 궤양성 대장염의 유병률을 높이고, 진행을 악화시키는 것으로 보고되었다. 따라서 본 연구에서는 커큐민이 비만에 의한 대장염의 진행을 억제하는지에 대해 조사하였다. 비만을 유도하기 위해 고지방 식이로 마우스를 사육하였고, 커큐민의 염증억제 효과를 확인하기 위해 고지방 식이와 함께 커큐민을 섭취시켰다. 궤양성 대장염을 유도하기 위해서 DSS를 경구투여 하고 대장염의 임상 증상을 관찰하였다. 대장염의 진행을 확인하기 위해 질병활성지수와 결장의 길이를 측정하였다. 커큐민에 의한 대장염 완화를 조직학적으로 평가하기 위해 결장, 간, 복부지방의 조직표본을 제작하고 H&E 및 Alcian blue-PAS 염색법으로 분석하였다. 커큐민은 질병활성지수의 점수를 감소시키고, 결장의 길이가 짧아지는 것을 억제하는 것으로 확인하였다. 또한, 비만으로 악화된 궤양성 대장염의 결장 조직에서 염증세포 침윤과 점막손상을 억제하였다. 커큐민은 간의 지방증과 복부지방의 지방세포를 유의하게 감소시키는 것으로 확인하였다. 결론적으로 커큐민은 비만에 의한 대장염의 진행을 억제함으로써 궤양성 대장염을 치료할 수 있는 치료제로서 활용될 것으로 사료된다.

• Neonatal Medicine
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• 제16권2호
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• pp.221-233
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• 2009

목 적 : 신장에서 분비되어 적혈구를 생산하는 빈혈제로 알려진 에리스로포이에틴(Erythropoietin, EPO)은 단순히 피를 만드는 조혈기능 뿐 아니라 최근 신경계 보호 및 신경강화 효과가 있다고 발표되고 있지만 주산기 가사로 인한 저산소성 허혈성 뇌병증의 치료제로서 그 기전이 명확하게 밝혀지지 않았다. 저자들은 유전자 재조합 인 에리스로포이에틴(recombinant Human EPO, rHuEPO)을 이용하여 주산기 저산소성 허혈성 뇌병증의 치료제로서 N-methyl-D-aspartate (NMDA) 수용체와 관련된 흥분성 독성작용을 통한 조절 등 그 기전을 알아보고자 하였다. 방 법 : 재태기간 19일된 태아 백서의 대뇌피질 세포를 배양하여 정상산소군은 5% $CO_2$ 배양기(95% air, 5% $CO_2$)에 두었고, 저산소군과 농도별 뇌손상 전 rHuEPO 투여군(1, 10, 100 IU/mL)은 1% $O_2$ 배양기(94% $N_2$, 5% $CO_2$)에서 6시간 동안 뇌세포손상을 유도하였다. 세포성장과 생존력을 평가하기 위해 MTT 실험을 시행하였다. 동물 모델에서는 생후 7일된 신생백서의 좌측 총 경동맥을 결찰한 후 6개 군; 정상산소군, sham-operated군, 저산소-허헐성군, 저산소-허헐성+vehicle군, 저산소-허헐성 손상 전 rHuEPO 투여군, 저산소-허헐성 손상 후 rHuEPO 투여군으로 나누었고, 저산소-허헐성 손상은 특별히 제작한 통속에서 2시간 동안 8% $O_2$ (8% $O_2$, 92% $N_2$)에 노출시켰다. rHuEPO은 뇌손상 전후 30분에 체중 kg당 1000 IU를 투여하였고, 저산소-허헐성 손상 후 7일째 조직을 실험하였다. 적출한 조직으로 H&E 염색을 하여 뇌손상을 형태학적으로 관찰하였다. 세포배양 및 동물실험에서 NMDA 수용체의 아단위인 NR1, NR2A, NR2B, NR2C, NR2D를 이용하여 실시간 중합효소연쇄반응을 실시하였다. 결 과 : 저산소군에서 세포 생존률은 정상산소군보다 60% 감소하였으며, rHuEPO 투여군(1, 10 IU/mL)은 80% 증가하였다. rHuEPO 투여군(100 IU/mL)은 회복되지 않았다. 우측 반구 대비 좌측 반구의 범위는 정상산소군 98.9%, sham-operated군 99.1%, 저산소-허헐성군 57.1%, 저산소-허헐성+vehicle군 57.0%, 저산소-허헐성 손상 전 rHuEPO 투여군 87.6%, 저산소-허헐성 손상 후 rHuEPO 투여군 91.6%으로 나타났다. NMDA 수용체의 아단위 생체외 실험에서 실시간 중합효소연쇄반응의 결과 NMDA 수용체 아단위 mRNA의 발현은 rHuEPO 투여군에서 저산소군보다 모두 증가하였다. 결 론 : 본 연구에서 rHuEPO은 흥분성 독성작용과 관련되어 NMDA 수용체를 조절하면서 저산소성 허헐성 뇌손상을 보호하는 것을 알 수 있었다.

• Clinical and Experimental Pediatrics
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• 제45권7호
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• pp.862-874
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• 2002

목 적: H. pylori 감염 진단에 있어 최적 표준 조건은 위생검 조직에서 세균을 증명하는 것이다. 위생검 조직을 이용한 현재의 검사법으로는 초기 감염 또는 항균요법을 받은 후 위점막에 적은 수의 세균이 존재하거나 여기저기 산재하여 분포할 경우 H. pylori를 쉽게 발견할 수 없다. 본 연구에서는 위점막 조직을 이용한 H. pylori 검출법으로 전포매 면역 전자 현미경 검사법을 시행하여 이 검사를 요소분해효소 검사 및 면역블롯팅법과 비교하고자 하였다. 방 법 : 1996년 7월부터 1999년 7월까지 상부 위장관 증세를 주소로 경상대학교병원 소아과를 찾은 2-15세 사이의 환아 119명을 대상으로 위내시경을 시행 하여 위생검 조직검사, 요소분해효소 검사, 전포매 면역 전자현미경 검사, 면역블롯팅 검사를 시행하였다. 결 과 : 1) 전포매 면역 전자현미경 검사상 위 전정부에서는 111례(93.3%), 위 체부에서는 105례(88.2%)에서 H. pylori가 관찰 되었다. 대상 환아 119명 중 116명 (97.5 %)의 위 전정부 또는 위 체부에서 H. pylori가 검출되었다. 2) 위 전정부나 위 체부에서 세균이 관찰되지 않은 3명 중 2명은 H & E 염색검사에서 세균이 관찰되었고 3명 모두 요소분해효소 검사상 6시간내 양성반응 및 면역블롯팅 검사상 양성반응을 보였다. 3) 요소분해효소 검사는 위 전정부에서 73례(61.3%), 위 체부에서 102례(85.7%)가 양성이었고, 총 107례(89.9%)에서 위 전정부 또는 위 체부에서 양성반응을 보였다. 4) H & E 염색 검사상 위 전정부 9례(7.6%), 위체부 12례(10.1%)에서 균이 발견되었고, 위 전정부 또는 위 체부에서 균이 관찰된 경우는 총 13례(10.9%)였다. H & E 염색에서 세균이 관찰된 13례 모두 요소분해효소 검사 양성이었으며 대부분 1시간 이내에 색깔이 변한 빠른 양성 반응을 보였다. 그러나 위전정부 9례 중 1례, 위 체부 12례 중 3례에서는 광학 현미경상 세균이 관찰되었으나 면역 전자현미경 검사에서는 관찰할 수 없었다. 총 13례 중 2례에서는 위전정부 또는 위 체부 모두에서 면역 전자현미경 검사에서 세균을 관찰할 수 없었다. 5) 면역블롯팅 검사상 총 97명(81.5%)에서 양성반응이 관찰되었다. 결 론 : 전포매 면역 전자현미경 검사가 소아 H. pylori 진단법의 최적 표준으로 사용될 수도 있는 결과를 보여 주었지만, 이 검사 역시 세균이 위점막 전체에 고르게 분포하지 않는 특성 때문에 기본적으로 조직검사를 통한 검사 방법이 가지는 한계를 가지고 있다. 소아에서 상부 위장관 증상으로 위내시경 검사를 받는 환아 대부분에서 H. pylori를 검출할 수 있었다는 것은 소아에서 흔히 사용되는 H. pylori 감염 진단법의 재평가 필요성을 시사한다.

• 대한한의학회지
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• 제34권1호
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• pp.116-135
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• 2013

Objectives: This study was intended to clarify how Jakyakkamchobuja-tang (hereinafter referred to JKBT) affects mice of C57BL/10 whose osteoarthritis was induced by papain. Methods: Osteoarthritis was induced in mice by injecting papain in the knee joint. Mice were divided into 4 groups (n=6). The normal group were not treated at all whereas the control group (OAC-control) were induced for osteoarthritis by papain and oral medicated with 200 ul of physiological saline per day. The positive comparison group (OAC-$Joins^{(R)}$) were injected with papain and after 7 days, 100 mg/kg of $Joins^{(R)}$ were medicated with 200 ul of physiological saline mixed. The experimental group (OAC-JKBT) were injected with papain and after 7 days were medicated with 400 mg/kg of JKBT mixed with 200 ul of physiological saline. OAC-$Joins^{(R)}$ and OAC-JKBT were oral medicated for each substance for a total of 4 weeks, once per day. After experiments (from 1 week after injection of papain to 4 weeks elapsed), the function of liver and kidney, inflammation cytokine values within serum, degree of revelation for inflammation cytokine genes, immune cells within blood, metabolism of arachidonic acid and amount of cartilage were measured and histopathological variations for knee joint structures were observed. Results: Functions of liver and kidney were not affected. IL-$1{\beta}$ (interleukin-$1{\beta}$), MCP-1 (monocyte chemoattractant protein-1) and TNF-${\alpha}$ (tumor necrosis factor-${\alpha}$) were significantly reduced and IL-6 (interleukin-6) was also reduced but not significantly. After analyzing inflammation cytokine in joints with mRNA (messenger ribonucleic acid), revelation of IL-6, TNF-${\alpha}$, COX-2 (cyclooxygenase-2) and iNOS-II (inducible nitric oxide synthase-II) were all significantly reduced. Revelation of IL-$1{\beta}$ gene was also reduced but not significantly. Neutrophil for WBC (white blood cell) within serum was significantly reduced; monocyte was also reduced but not significantly. PGE2 (prostaglandin E2), TXB2 (thromboxane B2) were significantly reduced and LTB4 (leukotriene B4) was also reduced but not significantly. Destruction of cartilage on micro CT (computed tomography)-arthrography was reduced but had no significant differences. In terms of histopathology, infiltration of inflammation, proliferation of synovial membrane, subsidence of cartilage and bone due to penetration of excessive formation of synovial cell and destruction of cartilage were small (H&E (hematoxylin and eosin), safranine O staining). Conclusions: Based on these results, Jakyakkamchobuja-tang (JKBT) is believed to be useful for suppressing the progress of osteoarthritis and its treatments because of its anti-inflammatory effects and alleviation of pain with histopathological effective efficacy.

• Toxicological Research
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• 제29권3호
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• pp.173-179
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• 2013

In-utero exposure to valproic acid (VPA) has been known as a potent inducer of autism spectrum disorder (ASD), not only in humans, but also in animals. In addition to the defects in communication and social interaction as well as repetitive behaviors, ASD patients usually suffer from gastrointestinal (GI) problems. However, the exact mechanism underlying these disorders is not known. In this study, we examined the gross GI tract structure and GI motility in a VPA animal model of ASD. On embryonic day 12 (E12), 4 pregnant Sprague-Dawley (SD) rats were subcutaneously injected with VPA (400 mg/kg) in the treatment group, and with phosphate buffered saline (PBS) in the control group; the resulting male offspring were analyzed at 4 weeks of age. VPA exposure decreased the thickness of tunica mucosa and tunica muscularis in the stomach and ileum. Other regions such as duodenum, jejunum, and colon did not show a significant difference. In high-resolution microscopic observation, atrophy of the parietal and chief cells in the stomach and absorptive cells in the ileum was observed. In addition, decreased staining of the epithelial cells was observed in the hematoxylin and eosin (H&E)-stained ileum section. Furthermore, decreased motility in GI tract was also observed in rat offspring prenatally exposed to VPA. However, the mechanism underlying GI tract defects in VPA animal model as well as the association between abnormal GI structure and function with ASD is yet to be clearly understood. Nevertheless, the results from the present study suggest that this VPA ASD model undergoes abnormal changes in the GI structure and function, which in turn could provide beneficial clues pertaining to the pathophysiological relevance of GI complications and ASD phenotypes.

• 한방재활의학과학회지
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• 제25권2호
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• pp.15-35
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• 2015

Objectives This study was performed to investigate the effects of Bujasasim-tang ethanol extract (BST) on oxidative stress, inflammation and osteoarthritic rat model. Methods To ensure safety of BST, heavy metal levels were measured and cytotoxicity test was done. In vitro, To evaluate antioxidative effects of BST, total phenolic contents, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activity, reactive oxygen species (ROS) levels were measured. Also, to evaluate anti-inflammatory effects of BST treated group, total nitric oxide (NO) and pro-inflammatory cytokines (IL-$1{\beta}$, IL-6, TNF-${\alpha}$) levels were measured in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In vivo, We injected MIA $50{\mu}l$ (60 mg/ml) into knee joints of rats to induce osteoarthritis. Rats were divided into total 3 groups (normal, control, BST treated group, each n=7). Normal group was not treated at all without inducing osteoarthritis and taken normal diet. Control group was induced osteoarthritis by MIA and taken with 2 ml of distilled water once a day for 4 weeks. BST treated group was induced osteoarthritis by MIA and taken BST 2 ml (200 mg/kg/mouse) once a day for 4 weeks. We evaluated dynamic weight bearing with the Incapacitance Test Meter. At the end of experiment, the rats were sacrificed to observe the functions of liver and kidney, changes of WBC, neutrophil, lymphocyte, monocyte levels in blood, to evaluate the levels of pro-inflammatory cytokines, tissue inhibitor of metallopreteinases-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), prostaglandin $E_2$ ($PGE_2$), leukotriene $B_4$ ($LTB_4$) within serum. We observed change of articular structures by Hematoxylin & Eosin (H&E), safranin-O staining method and measured amount of cartilage by micro CT-arthrography. Statistical analysis was done by unpaired student's t-test with significance level at p<0.05 in SPSS 11.0 for windows. Results 1. Safety of the BST was identified. 2. AST, ALT, BUN, creatinine levels of BST treated group were within normal limit. In vitro, 1. DPPH and ABTS free radical scavenging activities of BST showed dose-dependent increase. 2. ROS production were significantly decreased. 3. Total nitric oxide (NO) and IL-$1{\beta}$ production were decreased. 4. IL-6 and TNF-${\alpha}$ production were significantly decreased. In vivo, 1. Weight bearing ability was significantly increased. 2. WBC, neutrophil, lymphocyte, monocyte levels in blood were decreased. 3. IL-$1{\beta}$ and TNF-${\alpha}$ levels in serum were significantly decreased. and the IL-6 level was decreased. 4. TIMP-1, MMP-9, $LTB_4$, $PGE_2$ levels in serum were significantly decreased. 5. Cartilage volume of BST treated group was significantly increased. Also changes of cartilage, synovial membrane, fibrous tissue were suppressed. Conclusions The results obtained in this study Bujasasim-tang have effects of antioxidative, anti-inflammatory, relieve pain and protection of cartilage. Therefore we expect that Bujasasim-tang is effective treatment for osteoarthritis.

• 한방재활의학과학회지
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• 제21권2호
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• pp.63-85
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• 2011

Objectives : This study was carried out to know the effects of Danggwisayeokgaohsuyusaenggang-tang(hereinafter referred to DST) on arthritis induced by collagen on DBA/1 OlaHsd mice. Methods : For this purpose, DST was orally administered to mouse with arthritis induced by collagen II. Cytotoxicity, high performance liquid chromatograph(HPLC) analysis, arthritis index, value of immunocyte in draining lymph node and paw joint, cytokine were measured in vivo. Results : 1. The cytotoxicity against human fibroblast cells(hFCs) was not measured in any concentration. 2. In HPLC analysis, There are high peak patterns at 8 minute(min), 12 min, 35 min, 45 min. 3. The arthritis index was decreased significantly. 4. The degree of arthritis induced damage of joint of DST group is slight compared with control group in histopathologic observation(Hematoxylin and eosin stain(H&E), Masson's trichrome(M-T) staining). 5. In total cell counts of draining lymph node(DLN) and paw joint, the cells in DLN decreased significantly on DST 200 mg/kg and the cells in paw joint decreased significantly on 200 mg/kg and 50 mg/kg. 6. In DLN, $CD4^+/CD25^+$, $CD3^+/CD69^+$, major histocompatibility complex(MHC), class-II/$CD11c^+$ cells decreased significantly on DST 200 mg/kg and 50 mg/kg $CD3^+/CD8^+$ cells decreased significantly on DST 200 200 mg/kg, $CD4^+$, $CD3^+/CD44^+$ cells decreased. 7. In paw joints, $CD4^+$, $CD11b^+/Gr-1^+$ cells decreased significantly on DST 200 mg/kg and 50 mg/kg. 8. In joints, levels of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, cyclo-oxygenase-2(COX-2), NOS-II were decreased on DST 200 mg/kg and DST 50 mg/kg. 9. In analysing of cytokine in CD3/CD28 activated spleen, IL-17 was decreased significantly, IL-4 was increased significantly $INF-{\gamma}$ was decreased on DST 200 mg/kg. 10. In analysing of cytokine in collagen activated spleen, IL-17 were decreased significantly, IL-4 was increased significantly. Conclusions : This results demonstrated that DST suppressed the inflammatory progression of collagen-induced arthritis(CIA) mice and supported further studies are required to survey continuously in looking for the effective substance and mechanism in the future.