• Biomolecules & Therapeutics
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• 제22권6호
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• pp.497-502
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• 2014

In the present study, we found that the natural compound arctigenin inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production in rat primary astrocytes. Since hemeoxygenase-1 (HO-1) plays a critical role as an antioxidant defense factor in the brain, we examined the effect of arctigenin on HO-1 expression in rat primary astrocytes. We found that arctigenin increased HO-1 mRNA and protein levels. Arctigenin also increases the nuclear translocation and DNA binding of Nrf2/c-Jun to the antioxidant response element (ARE) on HO-1 promoter. In addition, arctigenin increased ARE-mediated transcriptional activities in rat primary astrocytes. Further mechanistic studies revealed that arctigenin increased the phosphorylation of AKT, a downstream substrate of phosphatidylinositol 3-kinase (PI3K). Treatment of cells with a PI3K-specific inhibitor, LY294002, suppressed the HO-1 expression, Nrf2 DNA binding and ARE-mediated transcriptional activities in arctigenin-treated astrocyte cells. The results collectively suggest that PI3K/AKT signaling pathway is at least partly involved in HO-1 expression by arctigenin via modulation of Nrf2/ARE axis in rat primary astrocytes.

• 대한본초학회지
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• 제22권4호
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• pp.253-260
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• 2007

Objectives : Intracerebral hemorrhage (ICH) is characterized by breakdown of blood vessels within the brain parenchyma. Fundamental therapeutic strategies for ICH, particularly those aimed at neuroprotection, have to be established. So in this experiment, the effects of Woowhangchongshim-won, a traditional prescription formula for treating Cerebral Apoplexy in Asian countries, were investigated. Methods : After intraperitoneal injection of chloralhydrate, rats were placed in a stereotaxic frame. ICH was induced by injection of 1 U collagenase type IV and drug was administered orally for 10 days. The molecular profile of cerebral hemorrhage in rat brain tissue was measured using micro array technique to identify up- or down- regulated genes in brain tissue. These genes induced by brain damage were mainly concerned with general metabolic process such as primary metabolic process, cellular metabolic process, macromolecule metabolic process, and biosynthetic process. Results : The number of genes increased in control and not-changed in experiment was 374, and decreased in control and not-changed in experiment was 527. We are concerned with genes that can be recovered by treatment with medicine, it is especially interesting to above types of genes. Conclusions : Upon medicine treatment to the rat having cerebral hemorrhage, expressions of some genes were restored to normal level. Further analysis using protein interaction database identified some key molecules that can be used for elucidation of therapeutical mechanism of medicine in future.

• 대한핵의학회지
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• 제1권2호
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• pp.27-34
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• 1967

근년(近年) 고등동물세포(高等動物細胞)에 있어서 유전자(遺傳子)의 본체(本體)인 DNA에서 RNA를 경과(經過)해서 특이적(特異的)인 단백질(蛋白質)의 생합성(生合成)에 도달(到達)하는 경로(經路)에 대(對)해서는 많은 연구(硏究)에 의해서 확립(確立)되어졌으나 그 조절기구(調節機構)에 대(對)해서는 불명(不明)한 점(點)이 많다. 개체(個體), 기관(器管), 세포내구조(細胞內構造) 급(及) DNA의 준위(準位)에서의 방사선(放射線)의 장해(障害)에 대(對)해서도 연구(硏究)되고 있으나 소위(所謂) 방사선감수성(放射線感受性) 급(及) 비감수성(非感受性)의 각장기(各臟器)에서 분리(分離)한 Chromatin (DNA-Histone-잔여단백(殘餘蛋白)의 고차구조결합체(高次構造結合體)에 대(對)한 DNA, RNA, 전단백질(全蛋白質)과 유전수식체(遺傳修飾體)라고 생각되는 Histon-단백(蛋白)의 화학조성(化學組成)을 검출(檢出)했으며 겸(兼)해서 chromatin의 생물활성(生物活性)인 RNA 합성능(合成能)(priming activity)에 대(對)한 방사선(放射線)의 영향(影響)을 조사(調査)하는데 의의(意義)가 있다. 전리방사선(電離放射線) 조사(照射)에 의해서 생체(生體)의 DNA의 합성조해(合成阻害)가 잘 알려진 사실(事實)이나 분화(分化)한 생체조직(生體組織)에서의 DNA의 합성(合成)보다도 일반대사(一般代謝)에 중요(重要)한 역할(役割)을 한다는 것도 생각된다. 세포(細胞)의 대사(代謝)는 내분비계등(內分泌系等)의 "Effector-DNA-RNA-단백합성(蛋白合成)이라는 정보유전기구(情報遺傳機構)에 의해서 제어(制禦)되어 있다. 이 연구(硏究)는 방사선생물학상(放射線生物學上) 중요(重要)한 것은 논할(論) 필요(必要)도 없으며 방사선동위원소표지화합물(放射線同位元素標識化合物)을 사용(使用)하여 생화학적(生化學的)으로 추구(推究)하였다.

• 대한핵의학회지
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• 제26권1호
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• pp.14-25
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• 1992

Thallium-201 $(^{201}T1)$ SPECT studies were performed on a normal volunteer and 12 patients with intracerebral lesions: 3 patients with gliomas, 3 patients with meningiomas, 1 patient each with metastatic tumor, brain abscess, and cerebral infarction, and 3 postirradiation patients. (2 with metastatic tumors, 1 with lymphoma). A $^{201}T1$ index, based on the ratio of $^{201}T1$ uptake in the brain lesion versus the homologous contralateral brain, was calculated and compared with tumor histology and CT/MRI findings. The SPECT $^{201}T1$ scan showed minimal uptake of tracer in a normal brain. There was substantial uptake of $^{201}T1$ in high-grade gliomas (index>1.5) with little uptake in low-grade lesions. A previously irradiated patient with recurrent astrocytoma, in whom MRI study was unable to distinguish tumor recurrence from necrosis, showed the lesions with high $^{201}T1$ indices in both hemispheric regions (2.50/1.93), suggesting tumor recurrence. Two meningiomas and a metastatic tumor showed varying degrees of $^{201}T1$ uptake (index $1.71\sim8.15$), revealing that $^{201}T1$ uptake is not exclusive to high-grade gliomas. In 2 postirradiation patients with metastatic tumors, no abnormal $^{201}T1$ uptake was found in the cerebral lesions, shortly after the initiation of radiation therapy or despite the persistence of enhancing lesions-though improved-on MR images, suggesting that $^{201}T1$ uptake may reflect the metabolic and possibly clonogenic activities of tumors and the brain $^{201}T1$ SPECT imaging might be valuable for the evaluation of tumor responsiveness to the therapy and for early detection of tumor recurrence. A patient with brain abscess on antibiotic treatment, showig increased uptake of $^{201}T1$ in the resolving lesions (index 2.87/1.52) is discussed. In a patient with cerebral infarction, there was no abnormal uptake of $^{201}T1$ in infarcted tissue. When using a threshold index of 1.5, correlation rate between $^{201}T1$ uptake and contrast enhancement of the cerebral lesions on CT/MRI was 73% (8/11). In conclusion, the brain $^{201}T1$ SPECT imaging may be useful for assessment of tumor response to the therapy and to predict low-or high-grade lesions.

• 대한방사선기술학회지:방사선기술과학
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• 제38권1호
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• pp.17-21
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• 2015

소아백혈병의 치료방법 인 조혈모세포이식법의 전처치 방법으로서 항암제와 함께 대표적으로 사용되고 있는 전신방사선조사에 대하여 치료를 시행하기 전 정량적인 인체장기에 대한 선량을 평가하고자 하였다. 모의실험 프로그램 MCNPX를 사용하여 가상의 공간에서 소아용 모의피폭체를 대상으로 조직보상체의 재질을 변화시켜 실험을 진행하였다. 그 결과 첫째, 평균피부선량은 조직보상체의 재질에 따라 Plexiglass는 74.60 mGy/min, Al은 73.96 mGy/min, Cu는 72.26 mGy/min, Pb의 경우 67.90 mGy/min을 보였다. 둘째, 심부선량은 조직보상체 재질에 상관없이 갑상선, 생식선, 소화기계, 머리, 폐, 신장의 순으로 높게 나타났다. 끝으로 조직보상체와 환자와의 거리는 50 cm 이격시켰을 때가 이상적인 것으로 분석되었다. 본 연구결과를 토대로 할 때, 조직보상체 Al, Cu, Pb은 현재 사용되고 있는 Plexiglass 재질을 대체할 수 있을 것으로 판단된다.

• Archives of Plastic Surgery
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• 제37권4호
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• pp.485-488
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• 2010

Purpose: Paragonimiasis is infectious disease occurred by Paragonimus Westermani, which invades into human body as a final host. Habitual eating the freshwater crab or crawfish unboiled is one of the reason of infection. Paragonimiasis raged in 1970s in Korea, Japan, China and other Asian countries but the incidence decreased rapidly. Once people eat infected second host, parasite penetrates the duodenal wall and migrates to the lung. During this migration period, the parasite can migrate to other organ, such as brain, spinal cord, liver and subcutaneous tissue, but the cases are rarely reported. The objective of our study is to present our experience of the ectopic migration of parasite to the subcutaneous tissue of the abdomen, which was easily treated with excision and Praziquantel medication. Methods: A 59-year-old woman who likes eating unboiled freshwater crab was diagnosed as Paragonimiasis 15 months ago. Her symptoms were fever and cough, and she was treated with Praziquantel medication. 3 months after discharge, she visited our hospital with left pleuritic chest pain, cough with fever, and palpable mass formation on left lower quadrant of the abdomen. Wedge resection of the left lung and Praziquantel medication was maintained for a week. Nevertheless, fever persisted after the treatment. The patient received total excision of the abdominal soft tissue mass, and the fever was relieved. Results: Pathologic findings of the mass showed multiple cyst and abscess formation with crystal structure which is suspicious parts of the parasite or calcified egg shells. Uncontrolled fever was relieved after the operation, and there was no evidence of recurrent Paragonimiasis and ectopic migration for 1 year follow up period. Conclusion: Ectopic migration of Paragonimus is rare, but multiple organ can be involved. Patient with Paragominiasis who was refractory in fever control after Praziquantel medication or surgical evaluation of the lung should be considered as ectopic migration of the Paragonimiasis.

• Parasites, Hosts and Diseases
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• 제54권1호
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• pp.15-20
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• 2016

Toxoplasmosis is an important zoonotic disease that can cause abortion in humans and animals. The aim of this study was isolation and subsequent genotyping of Toxoplasma gondii isolates in ovine aborted fetuses. During 2012-2013, 39 ovine aborted fetuses were collected from sheep flocks in Khorasan Razavi Province, Iran. The brain samples were screened for detection of the parasite DNA by nested PCR. The positive brain samples were bioassayed in Webster Swiss mice. The serum samples of mice were examined for T. gondii antibodies by IFAT at 6 weeks post inoculation, and T. gondii cysts were searched in brain tissue samples of seropositive mice. The positive samples were genotyped by using a PCR-RLFP method. Subsequently, GRA6 sequences of isolates were analyzed using a phylogenetic method. The results revealed that T. gondii DNA was detected in 54% (20/37, 95% CI 38.4-69.0%) brain samples of ovine aborted fetuses. In bioassay of mice, only 2 samples were virulent and the mice were killed at 30 days post inoculation, while the others were non-virulent to mice. The size of cysts ranged $7-22{\mu}m$. Complete genotyping data for GRA6 locus were observed in 5 of the 20 samples. PCR-RLFP results and phylogenetic analysis revealed that all of the isolated samples were closely related to type I. For the first time, we could genotype and report T. gondii isolates from ovine aborted fetuses in Khorasan Razavi Province, Iran. The results indicate that the T. gondii isolates are genetically related to type I, although most of them were non-virulent for mice.

• Journal of Periodontal and Implant Science
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• 제37권3호
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• pp.553-562
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• 2007

Osteoblasts regulate osteoclastogenesis by production of various cytokines. Aggregatibacter(A) ac-tinomycetemcomitans is one of periodontopathogens which invades gingival tissue. Therefore, clarifying the effect of alive A. actinomycetemcomitans on osteoblasts is important to understand the mechanism of alveolar bone resorption in periodontitis. We investigated induction of osteoclastogenesis-inducing cytokines, adherence, and invasion by A. actinomycetemcomitans in osteoblasts. Osteoblasts were isolated from mouse calvaria and expression of cytokines was determined by RT-PCR. When the ratio of the number of A. actinomycetemcomtians to the number of osteoblasts was 10:1, 50:1 and 100:1, RANKL mRNA expression was increased. A. actinomycetemcomitans also increased expression of macrophage inflammatory protein (MIP) -1${\alpha}$, interleukin (IL)-1${\beta}$, and tumor necrosis factor (TNF)-${\alpha}$. A. actinomycetemcomitans attached to and invaded osteoblasts at ratio of 1000:1. These results suggest that A. actinomycetemcomitans increases osteoclastogenesis-inducing ability of osteoblasts by stimulating the expression of RANKL, MIP-1${\alpha}$,IL-1${\beta}$, and TNF-${\alpha}$ and that invasion of A. actinomycetemcomitans provides a means by which the bacteria escape from immune system and antibiotic therapy.

• Toxicological Research
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• 제31권4호
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• pp.347-354
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• 2015

Excess manganese (Mn) is neurotoxic. Increased manganese stores in the brain are associated with a number of behavioral problems, including motor dysfunction, memory loss and psychiatric disorders. We previously showed that the transport and neurotoxicity of manganese after intranasal instillation of the metal are altered in Hfe-deficient mice, a mouse model of the iron overload disorder hereditary hemochromatosis (HH). However, it is not fully understood whether loss of Hfe function modifies Mn neurotoxicity after ingestion. To investigate the role of Hfe in oral Mn toxicity, we exposed Hfe-knockout ($Hfe^{-/-}$) and their control wild-type ($Hfe^{+/+}$) mice to $MnCl_2$ in drinking water (5 mg/mL) for 5 weeks. Motor coordination and spatial memory capacity were determined by the rotarod test and the Barnes maze test, respectively. Brain and liver metal levels were analyzed by inductively coupled plasma mass spectrometry. Compared with the water-drinking group, mice drinking Mn significantly increased Mn concentrations in the liver and brain of both genotypes. Mn exposure decreased iron levels in the liver, but not in the brain. Neither Mn nor Hfe deficiency altered tissue concentrations of copper or zinc. The rotarod test showed that Mn exposure decreased motor skills in $Hfe^{+/+}$ mice, but not in $Hfe^{-/-}$ mice (p = 0.023). In the Barns maze test, latency to find the target hole was not altered in Mn-exposed $Hfe^{+/+}$ compared with water-drinking $Hfe^{+/+}$ mice. However, Mn-exposed $Hfe^{-/-}$ mice spent more time to find the target hole than Mn-drinking $Hfe^{+/+}$ mice (p = 0.028). These data indicate that loss of Hfe function impairs spatial memory upon Mn exposure in drinking water. Our results suggest that individuals with hemochromatosis could be more vulnerable to memory deficits induced by Mn ingestion from our environment. The pathophysiological role of HFE in manganese neurotoxicity should be carefully examined in patients with HFE-associated hemochromatosis and other iron overload disorders.

• Journal of Korean Neurosurgical Society
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• 제63권2호
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• pp.163-170
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• 2020

Objective : Milk fat globule-epidermal growth factor VIII (MFG-E8) may play a key role in inflammatory responses and has the potential to function as a neuroprotective agent for ameliorating brain injury in cerebral infarction. This study aimed to determine the role of MFG-E8 in brain injury in the subacute phase of cerebral ischemia in a rat model. Methods : Focal cerebral ischemia was induced in rats by occluding the middle cerebral artery with the modified intraluminal filament technique. Twenty-four hours after ischemia induction, rats were randomly assigned to two groups and treated with either recombinant human MFG-E8 or saline. Functional outcomes were assessed using the modified Neurological Severity Score (mNSS), and infarct volumes were evaluated using histology. Anti-inflammation, angiogenesis, and neurogenesis were assessed using immunohistochemistry with antibodies against ionized calcium-binding adapter molecule 1 (Iba-1), rat endothelial cell antigen-1 (RECA-1), and bromodeoxyuridine (BrdU)/doublecortin (DCX), respectively. Results : Our results showed that intravenous MFG-E8 treatment did not reduce the infarct volume; however, the mNSS test revealed that neurobehavioral deficits were significantly improved in the MFG-E8-treated group than in the vehicle group. Immunofluorescence staining revealed a significantly lower number of Iba-1-positive cells and higher number of RECA-1 in the periinfarcted brain region, and significantly higher numbers of BrdU- and DCX-positive cells in the subventricular zone in the MFG-E8-treated group than in the vehicle group. Conclusion : Our findings suggest that MFG-E8 improves neurological function by suppressing inflammation and enhancing angiogenesis and neuronal proliferation in the subacute phase of cerebral infarction.