• 대한한의학회지
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• 제31권1호
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• pp.81-92
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• 2010

Objectives: The objective of this study was to assess bra in activation and difference by LI11 or ST36 acupuncture stimulation using functional MRI (fMRI). Methods: A total of 10 healthy right-handed volunteers were studied. LI11 acupuncture and ST36 acupuncture stimulations were applied in order on the left. The block design paradigm of RARARA was used for the task, with R representing rest and A representing stimulation, and each period lasted 30 seconds. fMRI data were analyzed using SPM2. Results: The left LI11 acupuncture stimulation activated both sides of the inferior parietal lobule, the left side of the extra-nuclear, culmen and inferior semi-lunar lobules. On the right side, the nodule and midbrain regions were activated by the left LI11 acupuncture stimulation. The left ST36 acupuncture stimulation activated the right side of the superior frontal gyrus, middle frontal gyrus, superior parietal lobule, inferior semi-lunar lobule and pyramis. On the left side, the sub-gyral, middle temporal gyrus, fusiform gyrus, supramarginal gyrus, extra-nuclear, cingulate gyrus and fastigium regions were activated by the left ST36 acupuncture stimulation. Besides, both sides of the paracentral lobule, inferior parietal lobule, culmen, cerebellar tonsil and midbrain regions were activated. Conclusions: In conclusion, brain signal activation patterns according to acupoints were observed to differ, and ST36 acupuncture stimulation activated more regions than LI11. It is supposed that LI11 and ST36 acupuncture stimulations have an influence on motor function and sensory aphasia, and these stimulations thus represent potential for ocular motor dysfunction, discriminative touch or position sense disorder. Moreover, ST36 acupuncture stimulation activated the cingulate gyrus of the limbic system, so it seems to have an influence over autonomic functions.

• 대한약리학회지
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• 제21권2호
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• pp.128-141
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• 1985

실험적으로 명암에 적응시킨 백서의 뇌내 specific opiate binding과 ${\beta}-endorphin$ 함량 일중변동에 미치는 지속적인 암적응, phenobarbital 장기처리의 영향을 관찰하고 opiate recptor binding과 ${\beta}-endorphin$ 함량 양자간의 관계를 추구하여 다음과 같은 성적을 얻었다. 1. L : D, 12 : 12 주기에 적응시킨 대조군에서 maximum $(^3H)$-morphine binding과 뇌내 ${\beta}-endorphin$ 함량은 각각 22시 및 06시에 최고에 달하는 매우 특이한 일중변동을 보였고 24시간 평균 $(^3H)$-morphine binding 및 뇌내 ${\beta}-endorphin$ 함량은 각각 0.45+0.03 pmol/mg protein과 46.7+3.6 fmol/mg protein이었다. 2. D : D, 12 : 12 주기에 적응시킨 표본에서 maximum $(^3H)$-morphine binding과 뇌내 ${\beta}-endorphin$ 함량은 대조군에서와는 달리 02시 및 14시에 최고에 달하는 유의한 일증변동을 보였고, 24시간 평균 maximum $(^3H)$-morphine binding치는 0.36+0.03 pmol/mg protein으로 대조군에 비하여 유의하게 감소를 하였으며, 24시간 정균 뇌내 ${\beta}-endorphin$치는 35.9+3.1 fmol/mg protein으로 대조군에 비하여 유의한 감소를 보였다. 3. Phenobarbital처리 표본에서 maximum $(^3H)$-morphine binding과 뇌내 ${\beta}-endorphin$ 함량은 각각 02시 및 14시에 최고 그리고 14시 및 02시에 최저에 달하는 대조군과는 다른 일중변동을 보였고, 24시간 평균 maximum $(^3H)$-morphine binding치는 0.33+0.03 pmol/mg protein으로 대조군에 비하여 현저한 감소를 보였다. 4. 전 실험군에서 opiate receptor binding의 Kd치는 변동하지 않았다. 5. 전 실험군에서 maximum $(^3H)$-morphine binding은 ${\beta}-endorphin$ 함량과 유의한 역상관관계가 있었다. 이상의 실험성적은 phenobarbital이 뇌내 ${\beta}-endorphin$ 함량과 opiate수용체의 숫적변동을 일으켜 morphine의 약리적 작용을 변동시킬 수 있으며, 이와 더불어 opiate 수용체와 ${\beta}-endorphin$ 함량 일중변동을 변화시킬 수 있음을 보여준다.

• KSBB Journal
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• 제20권5호
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• pp.363-370
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• 2005

중추신경계의 신경간세포가 파킨슨병과 뇌졸중과 같은 퇴행성 뇌 질환의 치료뿐만이 아니라 신경세포 발생과정에서의 중요성 때문에 최근에 커다란 관심의 대상이 되고 있다. 중추신경계의 발생과정 동안에, 중뇌의 도파민 신경세포의 형성은 두 가지의 분자생물학적인 기작에 의해서 결정된다. 첫째로, FGF-8, sonic hedgehog 그리고 전사조절인자 인 Nurr1이 도파민 신경세포의 형질을 결정짓는다. 또 다른 기작으로는, 전사조절인자 인 $Lm{\times}lb$와 $Pt{\times}3$가 중요하게 관련되어있다. 특히 Nurr1이 결핍된 생쥐에서, 타이로신수산화효소 (Tyrosine bydroxylase, TH) 면역양성 세포들이 중뇌흑색질에서 발견되지 않으므로 Nurr1이 도파민 신경세포의 발생에 필수적임을 알 수 있다. 본 연구에서는 도파민 신경세포의 형질을 유도하는데 있어서 Nurr1이 매개하는 기작을 연구하기 위해서 레트로 바이러스를 이용하여 Nurr1을 도입한 무한증식 신경간세포를 사용하였다. Nurr1 유전자의 과발현 만으로는 신경간세포에서 도파민 신경세포의 형질을 유도하지는 못하지만, 레티노이드 (retinoid, RA)와 폴스콜린 (forskolin, FK)을 처리하여 TH와 방향성 L-아미노산 탈카르복시화효소 (aromatic L-amino acid decarboxylase, AADC) mRNA의 발현을 유도하였다. 또한, Nurr1 과발현 신경간세포를 사람 별아교세포와 공동배양 하여 TH 발현량을 많이 증가시켰다. 이러한 공동배양실험에서, RA와 FK를 처리하면 TH의 발현수준이 더욱 더 증가함을 발견하였다. 이러한 결과들은 Nurr1 유전자를 도입한 사람 신경간세포가 파킨슨병 환자들에게 세포이식을 통한 유전자 치료의 유용성을 시사하고 있다.

• Nuclear Medicine and Molecular Imaging
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• 제43권1호
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• pp.10-18
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• 2009

목적: 본 연구는 다중계위축증(MSA)과 원발성 파킨슨병(IPD)의 감별 진단을 위하여 $^{123}I$-FP-CIT SPECT를 사용하여 선조체내 도파민신경시스템 및 선조체외의 모노아민시스템을 평가하였다. 대상 및 방법: 총 13명의 IPD 환자(남:여=9:4, $65.5{\pm}5.3$세), 8명의 MSA 환자(남:여=6:2, $64.0{\pm}4.5$세), 정상인 12명(남:여=8:4, $63.3{\pm}5.7$세)에게 $^{123}I$-FP-CIT SPECT를 시행하였다. 도파민 운반체 분석을 위해 선조체내 미상핵과 전, 후피각에 관심영역을 설정하고 세로토닌 운반체 분석을 위해 시상하부와 뇌교에 관심영역을 각각 정한 뒤 각 부위에서 $^{123}I$-FP-CIT의 결합잠재능(binding potential, BP=V3")을 계산하였다. V3"는 비특이적 결합에 대한 특이 결합의 비율을 이용하여 구하였고 비특이적 결합 부위는 후두엽 영역에서 계수를 측정하였다. 결과: 선조체 전체 및 미상핵과 전후피각 각각에서의 도파민 운반체의 농도는 MSA와 IPD환자 모두에서 정상인에 비해 현저한 감소를 나타내었다(p<0.05). 특히 IPD환자 군에서는 후측 피각에서의 도파민 운반체 농도에 심한 감소를 보여 전후피각비가 정상군에 비하여 유의하게 증가되었으며($1.55{\pm}0.34$ vs. $1.29{\pm}0.06$, p=0.026), 미상핵/피각비은 증가된 양상을 보였으나 유의수준에 도달하지는 못하였다($1.24{\pm}0.20$ vs. $1.11{\pm}0.06$, p=0.23). MSA의 경우 전후피각비($1.32{\pm}0.19$)와 미상핵/피각비($1.07{\pm}0.25$)에서 정상군과 차이가 없었다. 세로토닌 운반체에 의한 뇌교에서의 섭취는 MSA환자군에서 정상군 및 IPD환자군에 비하여 감소되어 있는 경향을 나타내었으며(정상:$0.33{\pm}0.19$, IPD: $0.29{\pm}0.19$, MSA: $0.22{\pm}0.1$) 시상하부에서는 각 군에서 뚜렷한 차이가 없었다. 결론: 본 연구에서 $^{123}I$-FP-CIT SPECT 영상을 이용하여 IPD와 MSA환자의 선조체 도파민 운반체의 감소정도와 양상을 평가하고, 뇌교 및 시상하부에서의 세로토닌 운반체 섭취의 감소를 평가하였다. $^{123}I$-FP-CIT SPECT에 의한 선조체내 도파민 운반체 변화 및 뇌교에서의 세로토닌 운반체의 변화의 가시화 및 정량화는 MSA와 IPD의 조기 감별에 도움이 유용할 것이다.

• Journal of Acupuncture Research
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• 제21권3호
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• pp.145-167
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• 2004

Objective : Neuropathic pain can be caused by a partial peripheral nerve injury. This kind of pain is usually accompanied by spontaneous burning pain, allodynia and hyperalgesia. It is not clear that scolopendrid aqua-acupuncture can control neuropathic pain effectively. The purpose of this study is to examine if scolopendrid aqua-acupuncture may be effective to the neuropathic pain (mechanical allodynia, cold allodynia) in a rat model of neuropathic pain. Methods : To produce the model of neuropathic pain, under isoflurane 2.5% anesthesia, tibial nerve and sural nerve was resected. After the neuropathic surgery, the author examined if the animals exhibited the behavioral signs of allodynia. The allodynia was assessed by stimulating the medial malleolus with von Frey filament and acetone. Three weeks after the neuropathic surgery, scolopendrid aqua-acupuncture was injected at Hwando(GB30) one time a day for one week. After that the author examined the withdrawl response of neuropathic rats' legs by von Frey filament and acetone stimulation. And also the author examined c-fos in the midbrain central gray of neuropathic rats and the change of WBC count in the blood of neuropathic rats. Results & Conclusion : 1. The scolopendrid aqua-acupuncture injected at Hwando(GB30) decreased the withdrawl response of mechanical allodynia in SHA-1, SHA-2 and SAH-3 group as compared with control group. 2. The scolopendrid aqua-acupuncture injected at Hwando(GB30) decreased the withdrawl response of chemical allodynia(cold allodynia) in SHA-1, SHA-2 and SAH-3 group as compared with control group. 3. The scolopendrid aqua-acupuncture injected at Hwando(GB30) showed the significant difference between sham group and control group(p=0.01), sham and SHA-3 group(p=0.026), control group and SHA-1 group(p=0.01), control group and SHA-2 group(p=0.024) in the c-fos expression. 4. The scolopendrid aqua-acupuncture injected at Hwando(GB30) showed the significant difference between sham group and SHA-3 group(p=0.010), control group and SHA-3 group(p=0.006) in the WBC count.

• Journal of Acupuncture Research
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• 제26권6호
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• pp.67-76
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• 2009

Objectives : The purpose of this study is to examine if Radix Aconiti herbal acupuncture may be effective to the neuropathic pain(mechanical allodynia, cold allodynia) in a rat model of neuropathic pain. Methods : To produce the model of neuropathic pain, under isoflurane 2.5% anesthesia, L5 spinal nerve was ligated by 6-0 silk thread. After neurophathic surgery, the author examined if the animals exhibited the behavioral sign of allodynia. The allodynia was assessed by stimulating the medial malleolus with von frey filament and acetone. Three days after the neuropathic surgery, Radix Aconiti herbal acupuncture was injected at Hwando($GB_{30}$) one time per two days for 2 weeks. After that, the author examined the withdrawal response of neuropathic rats' legs by von frey filament and acetone stimulation. And also the author examined c-Fos in the midbrain central gray of neuropathic rats and the change of WBC, RBC, HGB, HCT count in the blood of neuropathic rats. Results : The Radix Aconiti herbal acupuncture injected Hwando($GB_{30}$) decreased the withdrawal response of mechanical allodynia that assessed with von frey filament in RA1-$GB_{30}$, RA2-$GB_{30}$ group as compared with control group. The Radix Aconiti herbal acupuncture injected Hwando($GB_{30}$) decreased the withdrawal response of chemical allodynia(cold allodynia) that assessed with acetone in RA1-$GB_{30}$, RA2-$GB_{30}$ group as compared with control group. The Radix Aconiti herbal acupuncture injected Hwando($GB_{30}$) showed the significant between control group and RA2-$GB_{30}$ group in the c-Fos expression. The Radix Aconiti herbal acupuncture injected Hwando($GB_{30}$) did not show the significant between control group and RA1-$GB_{30}$ group, RA2-$GB_{30}$ group and RA3-$GB_{30}$ group in the WBC, RBC, HGB, HCT count. Conclusions : We have noticed that Radix Aconiti herbal acupuncture at Hwando($GB_{30}$) decreased mechanical allodynia and cold allodynia in the model of neuropathic pain compared with the control group. C-fos expression in the central gray of that group was also decreased compared with the control group. This study can be used as a basic resource on a study and a treatment of pain.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.14-40
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• 2002

15-Deoxy-${\Delta}^{12, 14}$-prostaglandin $J_2$ (15-deoxy-$PGJ_2$), a naturally occurring ligand activates the peroxisome proliferator-activated $receptor-{\gamma}(PPAR-{\gamma}$). Activation of $PPAR-{\gamma}$ has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-$PGJ_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-$PGJ_2$ (0.2 to 1.6 ${\mu}M$) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/ml). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-$PGJ_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-$PGJ_2$(0.8 ${\mu}M$) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-$PGJ_2$ on the expression of p38 MAP kinase and activation of AP-1, The promoting ability of 15-deoxy-$PGJ_2$ did not occur through $PPAR-{\gamma}$, as synthetic PPAR-${\gamma}$ agonist andantagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), $PPAR-{\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and $PGE_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of f 5-deoxy-$PGJ_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-$PGJ_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 single pathway may be important in the promoting activity of 15-deoxy-$PGJ_2$ cells.

• 한국발생생물학회지:발생과생식
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• 제15권2호
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• pp.143-150
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• 2011

이 연구는 수중 운동, 균형 훈련과 복합 운동이 파킨슨 유발 흰쥐 모델에 미치는 영향을 관찰하기 위해 수산화도파민(6-hydroxydopamine)을 흰쥐의 좌측 내측전뇌다발에 주사하여 파킨슨 모델을 제작하였다. 실험동물은 수중 운동을 적용한 실험군 I, 균형 훈련을 적용한 실험군 II, 복합 운동(수중 운동+균형 훈련)을 적용한 실험군 III, 수술 후 표준사육장에서 운동을 적용하지 않은 대조군으로 배치하였다. 수술 후 7일, 14일, 21일에 실험동물의 중뇌 흑질의 도파민 세포감소를 관찰하기 위하여 TH(tyrosine hydroxylase)의 발현 양상을 관찰하였고, 행동학적 검사로 수술 후 1일, 7일, 14일,21일에 아포몰핀유도 회전 검사를 실시하였다. 실험 결과, 실험군들에서 대조군에 비하여 유의하게 높은 TH 발현과 아포몰핀유도 회전수를 보였다. 하지만 실험군들 사이에는 유의한 차이가 나타나지 않았다. 이상의 결과에서 파킨슨유발 흰쥐모델이 기능 회복에 수중 운동과 균형 훈련이 효과적임을 알 수 있었으며, 흑질 치밀부의 도파민성 신경섬유의 증감을 나타내는 TH의 발현에도 수중 운동과 균형 훈련이 효과적임을 알 수 있었다.

• Journal of Korean Neurosurgical Society
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• 제50권4호
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• pp.299-303
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• 2011

Objective : Brainstem metastases are rarely operable and generally unresponsive to conventional radiation therapy or chemotherapy. Recently, Gamma Knife Radiosurgery (GKRS) was used as feasible treatment option for brainstem metastasis. The present study evaluated our experience of brainstem metastasis which was treated with GKRS. Methods : Between November 1992 and June 2010, 32 patients (23 men and 9 women, mean age 56.1 years, range 39-73) were treated with GKRS for brainstem metastases. There were metastatic lesions in pons in 23, the midbrain in 6, and the medulla oblongata in 3 patients, respectively. The primary tumor site was lung in 21, breast in 3, kidney in 2 and other locations in 6 patients. The mean tumor volume was $1,517mm^3$ (range, 9-6,000), and the mean marginal dose was 15.9 Gy (range, 6-23). Magnetic Resonance Imaging (MRI) was obtained every 2-3 months following GKRS. Follow-up MRI was possible in 24 patients at a mean follow-up duration of 12.0 months (range, 1-45). Kaplan-Meier survival analysis was used to evaluate the prognostic factors. Results : Follow-up MRI showed tumor disappearance in 6, tumor shrinkage in 14, no change in tumor size in 1, and tumor growth in 3 patients, which translated into a local tumor control rate of 87.5% (21 of 24 tumors). The mean progression free survival was 12.2 months (range, 2-45) after GKRS. Nine patients were alive at the completion of the study, and the overall mean survival time after GKRS was 7.7 months (range, 1-22). One patient with metastatic melanoma experienced intratumoral hemorrhage during the follow-up period. Survival was found to be associated with score of more than 70 on Karnofsky performance status and low recursive partitioning analysis class (class 1 or 2), in terms of favorable prognostic factors. Conclusion : GKRS was found to be safe and effective for management of brainstem metastasis. The integral clinical status of patient seems to be important in determining the overall survival time.

• Journal of Acupuncture Research
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• 제24권5호
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• pp.137-150
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• 2007

Objectives : To find effects of acupuncture, electro-acupuncture, low level He-Ne laser therapy(LLLT) at $TE_5$, $GB_{41}$ in the neuropathic pain. We made experiment on rats ligated L5 spinal nerve like general herniation of nucleus pulposus(HNP). Methods : A model of neuropathic pain was made by isolating Left 5th lumbar spinal nerve of rats. Three days after the neuropathic surgery, acupuncture and LLLT, electro-acupuncture was injected at $TE_5$, $GB_{41}$ one time a day for a week. Each group was divided two. one is opposite side performed the surgery which is right, another is left side performed the surgery. After that, the author examined the withdrawal response of neuropathic rats' legs by van Frey filament and acetone stimulation. And also the author examined c-Fos, Nociceptin and KOR-3 in the midbrain central gray of neuropathic rats. Results : As we have observed the effect of mechanical allodynia, LT-R group were diminished on 6th day compared with control group, EA-L group, EA-R group and LT-L group were diminished on 7th day compared with control group. As we have observed the effect of cold allodynia, EA-R group were diminished on 6th day, 7th day compared with control group. As we have observed the effect of activity of c-Fos in the central gray part, EA-R group and LT-R group were diminished compared with control group. As we have observed the effect of activity of Nociceptin in the central gray part, EA-R group were a little increased compared with control group but it is not reliability. As we have observed the effect of activity of KOR-3 in the central gray part, EA-R group were significantly increased compared with control group. Conclusions : We have noticed that effect of acupuncture at opposite side of sickness and powerful stimulation could be more effective, because of EA-R group have more controllable effect all test we have done on the other hand EA-L group have only effect on mechanical allodynia. This study can be used in clinical therapy for neuropathic pain. But it is not reliability that Nociceptin have effectively to control pain. Therefore We have to follow up about that.