• 대한임상독성학회지
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• 제2권1호
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• pp.54-57
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• 2004

Disulfiram (tetraethylthiuram disulphid) is used in the treatment of chronic alcoholism since it causes an unpleasant aversive reaction to alcohol. It works by inactivating hepatic aldehyde dehydrogenase, leading to pronounced rise in the acetaldehyde concentration when ethanol is metabolized. Acetaldehyde causes alcohol sensitivity, which involve vasodilation associated with feeling of hotness and facial flushing, increased heart rate and respiration rates, lowered blood pressure, nausea, headache. One of its metabolites, diethyldithiocarbamate (DDC) can inhibit the enzyme dopamine $\beta$-hydroxylase (DBH), this may account for the profound refractory hypotension and hypothermia seen with the disulfiram-ethanol reaction (DER), resulting from norepinephrine depletion. This report is presents the case of a patient we met, who presented with hypothermia caused by the disulfiram-ethanol reaction, and along with a brief review of the subject.

• Applied Microscopy
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• 제30권2호
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• pp.193-204
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• 2000

Mongolian gerbil (Meriones unguiculatus)은 선천적으로 불완전한 뇌바닥동백고리와 특이한 콜레스테롤 대사를 가진 동물로서 수분의 섭취없이도 장기간 생존이 가능하기 때문에 최근 뇌신경학 연구방법에 많이 이용되는 동물이다. 따라서 본 연구는 mongolian gerbil을 절수 시켰을 때 시간의 경과에 따라 뇌에서의 catecholaminergic neuron의 형태적인 변화에 관하여 알아보고자 $50\sim80g$의 mongolian gerbil 25마리를 이용하여 5마리는 뇌도보를 작성하였으며 나머지는 정상군, 5일군, 10일군, 20일군으로 각각 5마리씩 나누어 TH, DBH, PNMT항체를 이용하여 면역조직화학염색하여 절수의 시간에 따른 뇌에서의 catecholaminer-gic neuron의 형태적인 변화를 광학 및 전자현미경적으로 관찰하여 다음과 같은 결론을 얻었다. 1. 정상군의 경우 시상하부의 제 3 뇌실주위에 있는 뇌실곁핵과 뇌실주위회백질에 TH면역반응세포들이 나타났고 이들의 신경세포돌기 및 신경섬유들도 많이 분포하였으나 20일군에서 감소되는 양상을 보였다. 2. 중뇌 및 교뇌에서는 catecholamine성 신경세포중 dopamine성 신경세포가 뚜렷히 관찰되었으나 noradrenalin성 신경세포는 약하게 관찰되었다. 3. 흑색질의 치밀부분과 배쪽피개영역에서 TH항체에 대한 면역반응을 보이는 Dopamine성 신경세포 밀집도가 높았으며 그물부분에서도 소수 관찰되었다. 그러나 이 부위에서 dopamine성 신경세포도 절수에 따라 5일군까지 신경세포체와 돌기 및 섬유들이 감소되었으나 10일군에서는 다시 증가하였으며 20일군에서부터 감소하는 양상을 보였다. 4. 절수에 의한 뇌의 TH면역반응세포체의 전자현미경적 소견은 정상군에 비해 5일군에서 핵의 농축 및 변형, 신경연접의 소실, 사립체의 감소, 축삭 수의 감소 등이 나타나 TH의 분비에 영향을 주는 것으로 보인다. 그러나 ER등의 변화는 크게 관찰할 수 없었다. 이러한 연구결과는 정상군의 경우 다른 동물과 유사했으나 다른 동물에서는 청색반점이나 교뇌부위에서 noradrenaline성 신경이 많다고 하였지만 본 연구에서는 그러한 차이를 발견하지 못했으며 이것은 동물간의 유전적, 환경적 차이로 사료된다. 그러므로 mongolian gerbil의 수분대사에 dopamine이 관여할 것으로 보고 탈수 질환모델로 개발하기 위한 기능적인 연구와 더불어 많은 형태학적인 연구가 병행되어야 할 것이다.

• Journal of Genetic Medicine
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• 제4권2호
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• pp.179-185
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• 2007

목 적:카테콜라민은 교감신경계에서 신경전달물질이며 스트레스자극에 의해 활성화된다. TH와 DBH는 카테콜라민 합성에 매우 중요한 효소이다. CRH는 스트레스 반응에서 방출되는 호르몬이다. 이번 연구의 목적은 부동스트레스가 흰쥐 뇌에서 TH, BDH와 CRH 유전자발현에 어떤 영향을 미치는가를 알아보기 위한 것이다. 방 법:2시간 동안 부동스트레스와 무처치 흰쥐의 뇌에서 TH, DBH와 CRH 유전자 발현량을 비교하였다. TH, DBH와 CRH 유전자 발현은 RT-PCR과 western blotting analysis에 의해 정량하였다. 결 과:부동스트레스 흰쥐 그룹의 뇌와 부신에서 TH와 DBH 유전자발현은 정상그룹보다도 약 2-3배 유의하게 증가하였으며, CRH유전자는 약 1.5배 유의하게 증가하였다. 결 론:이번 연구는 흰쥐의 뇌와 부신에서 TH, DBH와 CRH 유전자는 스트레스 자극에 의해 발현이 활성화됨을 확인할 수 있었다.

• Preventive Nutrition and Food Science
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• 제10권1호
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• pp.103-110
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• 2005

Opuntia ficus-indica, commonly known as prickly pear cactus, is commercially grown as a food and medicinal plant in Jeju Island, Korea. The crushed pads and fruits of Opuntia ficus-indica were dried in a freeze-dryer and ground into flour to be used for food materials. The major components of proximate compositions were part of a nitrogen free extract. The major minerals were Ca (4391.2-2086.9㎎%), K (1932.1-2608.7㎎%), and Mg (800.6-1984.8㎎%). The major amino acid was glutamic acid, comprising 16.3% of total amino acids in fruit and 25.2% in pad. Dihydroflavonols were identified as (+)-trans-dihydrokaempferol and (+)-trans-dihydroquercetin. Citric acid methyl esters extracted from fruits showed inhibitory activities against monoamine oxidase-B. The presence of trimethyl citrate has been reported in other plants, but 1,3-dimethyl citrate and 1-monomethyl citrate have not been previously reported. The results of pharmacological efficacy tests, including serum biochemical and hematological parameters, autonomic nervous system, anti-inflammatory, analgestic activity, anti-diabetic activity, antithrombotic, anticoagulant, dopamine beta-hydroxylase, monoamine oxidase activity, hyperlipidemia, the respiratory system, antigastic, and anti-ulcerative actions indicate that the fruit and pad of the Opuntia ficus-indica are rich sources of food and medicinal materials.

• 동국한의학연구소논문집
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• 제8권1호
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• pp.117-131
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• 1999

Yangkyuksanhoa-tang is frequently used for cerebrovascular accident(CVA). The present study was performed to investigate the effect of Yangkyuksanhoa-tang on the peri vascular immunoreactive nerve fiber of the basilar artery after experimentally induced subarachnoid hemorrhage(SAH). Sprague Dawley rats weighing between 350-400g were used. The SAH induced by injection of the fresh autologus heart blood(0.3-0.4ml) into the cisterna magna through the posterior atlanto-occipital membrane. Sample group was given a $3.3m{\ell}/kg/day$ of Yangkyuksanhoa-tang extracts for 2 days after SAH. The experimental animals divided into 48hrs after SAH. The changes of perivascular immunoreactive nerve fiber was examined by using indirect immunofluorescence method. The meshlike perivascular nerve fiber appeared in the basilar artery of normal rats. In basilar artery of SAH elicitated rat, the distribution of calcitonin gene-related peptide (CGRP)-immunoreactivity(IR) and vasoactive intestinal polypeptide(VIP)-IR of the perivascular nerve fiber were remarkably diminished, also dopamine beta hydroxylase(DBH)-IR, neuropeptide Y(NPY)-IR and serotonin-IR were diminished. In SAH elicitated rat with Yangkyuksanhoa-tang treatment, the CGRP-IR and VIP-IR degree were repaired as well as normal rat's, but DBH-IR, NPY-IR and serotonin-IR had no changes. These results provide the basic data to investigate the effect of Yangkyuksanhoa-tang on the vasospasm after SAH.

• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2003년도 제3회 국제심포지움 및 학술대회
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• pp.101-101
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• 2003

Main strategy for a treatment of Parkinson's disease (PD), due to a progressive degeneration of dopaminergic neurons, is a pharmaceutical supplement of dopamine derivatives or ceil replacement therapy. Both of these protocols have pros and cons; former exhibiting a dramatic relief but causing a severe side effects on long-term prescription and latter also having a proven effectiveness but having availability and ethical problems Embryonic stem (ES) cells have several characteristics suitable for this purpose. To investigate a possibility of using ES cells as a carrier of therapeutic gene(s), human ES (hES, MB03) cells were transfected with cDNAs coding for tyrosine hydroxylase (TH) in pcDNA3.1 (+) and the transfectants were selected using neomycin (250 $\mu /ml$). Expression of TH being confirmed, two of the positive clone (MBTH2 & 8) were second transfected with GTP cyclohydrolase 1 (GTPCH 1) in pcDNA3.1 (+)-hyg followed by selection with hygromycin-B (150 $\mu /ml$) and RT-PCR confirmation. By immune-cytochemistry, these genetically modified but undifferentiated dual drug-resistant cells were found to express few of the neuronal markers, such as NF200, $\beta$-tubulin, and MAP2 as well as astroglial marker GFAP. This results suggest that over-production of BH4 by ectopically expressed GTPCH I may be involved in the induction of those markers. Transplantation of the cells into striatum of 6-OHDA- denervated PD animal model relieved symptomatic rotational behaviors of the animals. Immunohistochemical analyses showed the presence of human cells within the striatum of the recipients. These results suggest a possibility of using hES cells as a carrier of therapeutic gene(s).

• 대한수의학회지
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• 제40권2호
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• pp.197-211
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• 2000

The pineal body have been known to be affected by superior cervical ganglia, and most of its nerve fibers containing peptidergic neurotransmitters have been considered to be originated from this ganglia. To confirm this relationships, some peptidergic neurotransmitters were identified in both of pineal body and superior cervical ganglia of the Korean native goat, which were divided into two group; breeding season and non-breeding season. The localizations of two catecholamine-synthesizing enzymes; tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH), were investigated by immunohistochemistry in the superior cervical ganglia and the pineal body of adult Korean native goats. Substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY) and galanin (GAL) were also identified in these organs by immunohistochemical and double immunofluorescent methods. In superior cervical ganglia, immunoreactivities for TH and DBH were confirmed in the same ganglion cells. The immunoreactivites for SP, VIP(only in male), NPY and GAL were identified in both of ganglion cell bodies and nerve fibers in the ganglia. CGRP immunoreactivity, however, was observed only in nerve fibers. Most NPY- and VIP-immunoreactive(IR) ganglion cells also contained TH. SP and TH were colocalized in the cell bodies, but not in the nerve fibers. TH immunoreactivity was shown in almost all of ganglion cells in the superior cervical ganglia. The immunoreactivity for NPY had some seasonal variation and was stronger in breeding season than in non-breeding season. In pineal body, lots of TH-IR fibers were observed throughout the parenchyma including the pineal stalk and most of them also contained DBH. SP- and NPY-IR fibers were also immunostained with TH or DBH. But a few SP- and NPY-IR fibers were not colocalized with TH or DBH. Exceptionally, a bipolar neuron-like cell was observed to be immunostained with NPY in the pineal body. A few CGRP and GAL-IR fibers were observed, while VIP-IR fibers were not present. It is concluded that most TH- and DBH-IR fibers as well as the peptidergic immunoreactive fibers of the pineal body might be originated from the superior cervical ganglia. Some peptidergic immunoreactive fibers, however, might be come from other regions of brain. We also suggest that NPY in pineal body plays a important role for pineal function. The seasonal variation of NPY immunoreactivity indicates that the synthesis and use of NPY may be different between in breeding and non-breeding seasons.

• Journal of Korean Neurosurgical Society
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• 제56권5호
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• pp.383-389
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• 2014

Objective : Neural tissue transplantation has been a promising strategy for the treatment of Parkinson's disease (PD). However, transplantation has the disadvantages of low-cell survival and/or development of dyskinesia. Transplantation of cell aggregates has the potential to overcome these problems, because the cells can extend their axons into the host brain and establish synaptic connections with host neurons. In this present study, aggregates of human brain-derived neural stem cells (HB-NSC) were transplanted into a PD animal model and compared to previous report on transplantation of single-cell suspensions. Methods : Rats received an injection of 6-OHDA into the right medial forebrain bundle to generate the PD model and followed by injections of PBS only, or HB-NSC aggregates in PBS into the ipsilateral striatum. Behavioral tests, multitracer (2-deoxy-2-[$^{18}F$]-fluoro-D-glucose ([$^{18}F$]-FDG) and [$^{18}F$]-N-(3-fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane ([$^{18}F$]-FP-CIT) microPET scans, as well as immunohistochemical (IHC) and immunofluorescent (IF) staining were conducted to evaluate the results. Results : The stepping test showed significant improvement of contralateral forelimb control in the HB-NSC group from 6-10 weeks compared to the control group (p<0.05). [$^{18}F$]-FP-CIT microPET at 10 weeks posttransplantation demonstrated a significant increase in uptake in the HB-NSC group compared to pretransplantation (p<0.05). In IHC and IF staining, tyrosine hydroxylase and human ${\beta}2$ microglobulin (a human cell marker) positive cells were visualized at the transplant site. Conclusion : These results suggest that the HB-NSC aggregates can survive in the striatum and exert therapeutic effects in a PD model by secreting dopamine.