• Journal of Preventive Medicine and Public Health
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• 제29권3호
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• pp.657-668
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• 1996

경상남도 일부 지역에서 60세 이상 노인들의 MMSE에 의한 인지 장애 유병률을 조사하고 인지 장애에 영향을 미치는 요인들을 조사하여 다음과 같은 성적을 얻었다. 1. MMSE에 의한 인지 장애의 유병률은 35.9%로 남자에서 18.4%, 여자에서 45.2%였다. 2. 인지 장애 유병률은 여자에서 유의하게 높았고(p=0.02) 무학력자와 문맹자의 인지 장애 유병률이 통계적으로 유의하게 높았다(p=0.03). 3.성별과 교육 수준에 따른 층화 분석에서 알루미늄의 인지 기능에 대한 독성 효과와 칼슘의 보호 효과에 대한 전체적으로 일정한 경향은 관찰되지 않았다(p>0.05). 4. 최종 분석 대상자 전체에서 음용수 중의 알루미늄과 인지 기능 검사 점수간의 상관 계수는 -0.066으로서 미약한 음의 상관관계에 있었으나 통계학적인 유의성은 보이지 않았고(p=0.434), 칼슘과 MMSE 점수와의 관계에서도 기대했던 바의 양의 상관관계는 관찰할 수 없었다.

• Biomolecules & Therapeutics
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• 제22권6호
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• pp.532-539
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• 2014

Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC ($50{\mu}mol/L$), gp120 (500 pmol/L) plus ddC ($50{\mu}mol/L$), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC ($50{\mu}mol/L$) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC ($50{\mu}mol/L$) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (> $25{\mu}m$), whereas ddC mainly affected small diameter DRG neurons (${\leq}25{\mu}m$). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.

• 생명과학회지
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• 제28권11호
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• pp.1332-1338
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• 2018

뇌신경 질환의 주요 원인이 되는 것으로 알려진 미세아교세포의 과도한 활성화에 의한 신경염증반응에서 풀무치 에탄올 추출물이 미세아교세포의 염증 반응에 미치는 영향을 검토하였다. 미세아교세포의 활성화를 유도하기 위해 LPS를 사용하였으며, LPS 처리에 의해 신경염증반응의 지표인 NO의 생성량과 이들을 조절하는 iNOS, COX-2의 발현이 증가됨을 확인 할 수 있었다. 그러나 풀무치 에탄올 추출물을 1시간 전처리 한 후 LPS를 처리한 경우 추출물의 농도에 의존적으로 이들의 발현량이 현저히 감소되는 것을 확인 하였다. 또한 LPS 처리로 인해 분비되는 염증성 cytokine들의 생성량도 풀무치 에탄올 추출물에 의해 현저히 억제 됨을 확인 할 수 있었다. 따라서 본 연구의 결과는 미세아교세포의 과도한 활성화로 인해 발생되는 뇌 신경질환의 치료 소재로서 풀무치 에탄올 추출물의 활성 가능성을 제시하였다.

• 생명과학회지
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• 제19권4호
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• pp.449-456
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• 2009

신경아세포종은 미분화된 신경외배엽 세포로부터 유래한 신경능세포에 의해 형성된 소아기에 보는 가장 많이 발생하는 악성 종양 중 하나이다. 신경아세포종인 Neuro-2a 세포는 신경세포의 분화, 세포사 억제 효능, 세포독성 검정 등에 활용되고 있다. Neuro-2a 역시 다른 신경아세종과 같이 염색체 변이를 가지고 있지만, 이에 대해 고밀도의 게놈수준에서 염색체 변이에 대해 보고된 바가 없다. 본 연구에서는 고집적 마이크로어레이(최소 43,000 개의 코딩, non-코딩 유전자 서열이 집적된 마이크로어레이)기반의 비교유전체보합법을 활용하여, 고해상도의 Neuro-2a 유전체 이상을 분석하였다. 마이크로 어레이 데이터는 Hidden Markov Model을 활용하여, 유전체 변이를 double loss, single loss, normal, single gain 그리고 amplification으로 나누어 분석하였다. Neuro2a는 MYCN 유전자의 증폭은 관찰되지 않았고, GDNF, BDNF, NENF등의 neurotrophic factor 가운데 NENF의 gain 현상이 관찰 되었다. 염색체의 이상은 4,8,10,11,15번에서 발견되었으며, 염색체 3,17,18,19에서는 전부 20개 미만의 염색체 이상이 발견되었다. 염색체 이상이 연속적으로 일어난 부위 중 gain으로서 가장 긴 부분은 Chr8:8,427,841-35,162,415의 약 26.7 Mb이며, single loss로서 가장 긴 곳은 Chr4:73,265,785-88,374,165의 약 15.1 Mb였다. 염색체의 위치는 UCSC 데이터베이스 (UCSC mm8, NCBI Build 36)에 근거하였다.

• 한국환경보건학회:학술대회논문집
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• 한국환경보건학회 2005년도 Proceedings of KSEH.Minamata Forum
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• pp.4-15
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• 2005

Methylmercury (MeHg) is an environmental pollutant with neurotoxic effects on the central nervous system. The major exposure route of MeHg to humans is via consumption of fish and shellfish which accumulate the chemical through the food web in an aquatic environment. Hair mercury level is an excellent marker for MeHg exposure. We have been conducting a survey on hair mercury contents among general populations from 14 districts to estimate the current Japanese MeHg exposure level. Total mercury levels of all hair samples collected (12923 in total) were analyzed by the oxygen combustion-gold amalgamation method using an atomic absorption mercury detector. Multiple regression analysis revealed that mercury levels were significantly correlated with several covariates, such as sex, age, the amount of daily intake of total fish/shellfish, a preference for certain fish such as tuna or bonito, and artificial waving. The geometric means for the population without artificial waving were 2.47 and 1.65 ${\mu}g/g$ for males (n = 5623) and females (n = 3470), respectively. Hair mercury levels varied with age, and the variations were more significant in males. Since the difference between sexes was not evident at younger ages, some hormonal control might also be involved in the mercury uptake by human hair. The average mercury levels in our hair samples varied among the sampling districts. Tuna is a major carnivorous fish with high mercury accumulations that is often consumed in Japan. The amount of fish consumption and the preference rate far tuna would appear to be responsible far the regional variation in hair mercury levels in Japan. Recently, a provisional tolerable weekly intake (PTWI) of MeHg was revised by 61st JECFA to 1.6 ${\mu}g/kg/week$, which was about half that of the Japanese standard, and corresponded to a hair level of 2.2 ppm. The distribution of hair mercury levels in Japanese populations in the present study indicated that 25% of the Japanese females of child-bearing age were estimated to be exposed to MeHg over the PTWI level. This would reflect the high Japanese consumption of marine products. However, not only mercury contamination, but also the nutritional benefit may have to be considered when discussing the risk involved in the current level of fish and shellfish consumption in Japan.

• 동의생리병리학회지
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• 제17권6호
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• pp.1500-1508
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• 2003

This study was performed to clarify the neurotoxic mechanism of nerve cells damage by brain ischemia. The cytotoxic effect of ischemia was determined by XTT assay, NR assay, superoxide dismutase(SOD) activity, amount of malondialdehyde(MDA), lactate dehydrogenase(LDH) activity, protein synthesis and tumor necrosis factor(TNF)-α activities after cerebral neurons derived from mouse were exposed to ischemia for 1∼30 minutes. In addition, the protective effect of extract of Daejo-whan(DJW) on ischemia-induced neurotoxicity was examined in these cultures. 1. Ischemia decreased cell number and viability by XTT assay or NR assay when cultured cerebral neurons were exposed to 95% N2/5% CO₂ for 1∼20 minutes in these cultures. 2. Ischemia decreased SOD and protein syntheses, but it increased amount of MDA and, LDH and TNF-α activities in these cultures. 3. In the neuroprotective effect of DJW extracts on cerebral neurons damaged by ischemia, DJW extracts increased SOD activity and protein synthesis. While, it decreased amount of MDA and, LDH and TNF-α activities after cerebral neurons preincubated with herb extracts. It suggests that brain ischemia has neurotoxicity on cultured mouse cerebral neurons, and the herb extract such as DJW was very effective in blocking the neurotoxicity induced by ischemia in cultured mouse cerebral neurons.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.597-603
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• 2015

Synthetic cannabinoids JWH-018 and JWH-250 in 'herbal incense' also called 'spice' were first introduced in many countries. Numerous synthetic cannabinoids with similar chemical structures emerged simultaneously and suddenly. Currently there are not sufficient data on their adverse effects including neurotoxicity. There are only anecdotal reports that suggest their toxicity. In the present study, we evaluated the neurotoxicity of two synthetic cannabinoids (JWH-081 and JWH-210) through observation of various behavioral changes and analysis of histopathological changes using experimental mice with various doses (0.1, 1, 5 mg/kg). In functional observation battery (FOB) test, animals treated with 5 mg/kg of JWH-081 or JWH-210 showed traction and tremor. Their locomotor activities and rotarod retention time were significantly (p<0.05) decreased. However, no significant change was observed in learning or memory function. In histopathological analysis, neural cells of the animals treated with the high dose (5 mg/kg) of JWH-081 or JWH-210 showed distorted nuclei and nucleus membranes in the core shell of nucleus accumbens, suggesting neurotoxicity. Our results suggest that JWH-081 and JWH-210 may be neurotoxic substances through changing neuronal cell damages, especially in the core shell part of nucleus accumbens. To confirm our findings, further studies are needed in the future.

• The Korean Journal of Pain
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• 제23권2호
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• pp.116-123
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• 2010

Background: Pamidronate is a potent inhibitor of osteoclast-mediated bone resorption. Recently, the drug has been known to relieve bone pain. We hypothesized that direct epidural administration of pamidronate could have various advantages over oral administration with respect to dosage, side effects, and efficacy. Therefore, we evaluated the neuronal safety of epidurally-administered pamidronate. Methods: Twenty-seven rats weighing 250-350 g were equally divided into 3 groups. Each group received an epidural administration with either 0.3 ml (3.75 mg) of pamidronate (group P), 0.3 ml of 40% alcohol (group A), or 0.3 ml of normal saline (group N). A Pinch-toe test, motor function evaluation, and histopathologic examination of the spinal cord to detect conditions such as chromatolysis, meningeal inflammation, and neuritis, were performed on the 2nd, 7th, and 21st day following administration of each drug. Results: All rats in group A showed an abnormal response to the pinch-toe test and decreased motor function during the entire evaluation period. Abnormal histopathologic findings, including neuritis and meningeal inflammation were observed only in group A rats. Rats in group P, with the exception of 1, and group N showed no significant sensory/motor dysfunction over a 3-week observation period. No histopathologic changes were observed in groups P and N. Conclusions: Direct epidural injection of pamidronate (about 12.5 mg/kg) showed no neurotoxic evidence in terms of sensory/motor function evaluation and histopathologic examination.

• Biomolecules & Therapeutics
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• 제17권1호
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• pp.47-56
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• 2009

Schizandra chinensis (S. chinensis) exhibits a harmless, 'adaptogen-type' effect leading to improvements in mental performance and learning efficacy in brain. Activated microglia contributes to neuronal injury by releasing neurotoxic products, which make it important to regulate microglial activation to prevent further cytological as well as functional brain damage. However, the effect of S. chinensis on microglial activation has not been examined yet. We have investigated the effects of four compounds (Gomisin A, Gomisin N, Schizandrin and Schizandrol A) from S. chinensis on lipopolysaccharide (LPS)-induced microglial activation. In this study, BV2 microglial cells were activated with LPS and the microglial activation was assessed by up-regulation of activation markers such as nitric oxide (NO), reactive oxygen species (ROS), and matrix metalloproteinase-9 (MMP-9). The results showed that all four compounds significantly reduced the intracellular level of ROS, the release of NO and MMP-9 as well as LPS-induced phosphorylation of ERK1/2. These results strongly suggested that S. chinensis may be useful to modulate inflammation-mediated brain damage by regulating microglial activation.

• Radiation Oncology Journal
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• 제38권1호
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• pp.35-43
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• 2020

Purpose: This retrospective study compares higher-dose whole-brain radiotherapy (hdWBRT) with reduced-dose WBRT (rdWBRT) in terms of clinical efficacy and toxicity profile in patients treated for primary central nervous system lymphoma (PCNSL). Materials and Methods: Radiotherapy followed by high-dose methotrexate (HD-MTX)-based chemotherapy was administered to immunocompetent patients with histologically confirmed PCNSL between 2000 and 2016. Response to chemotherapy was taken into account when prescribing the radiation dose to the whole brain and primary tumor bed. The whole brain dose was ≤23.4 Gy for rdWBRT (n = 20) and >23.4 Gy for hdWBRT (n = 68). Patients manifesting cognitive disturbance, memory impairment and dysarthria were considered to have neurotoxicity. A median follow-up was 3.62 years. Results: The 3-year overall survival (OS) and progression-free survival (PFS) were 70.0% and 48.9% with rdWBRT, and 63.2% and 43.2% with hdWBRT. The 3-year OS and PFS among patients with partial response (n = 45) after chemotherapy were 77.8% and 53.3% with rdWBRT, and 58.3% and 45.8% with hdWBRT (p > 0.05). Among patients with complete response achieved during follow-up, the 3-year freedom from neurotoxicity (FFNT) rate was 94.1% with rdWBRT and 62.4% with hdWBRT. Among patients aged ≥60 years, the 3-year FFNT rate was 87.5% with rdWBRT and 39.1% with hdWBRT (p = 0.49). Neurotoxicity was not observed after rdWBRT in patients aged below 60 years. Conclusion: rdWBRT with tumor bed boost combined with upfront HD-MTX is less neurotoxic and results in effective survival as higher-dose radiotherapy even in partial response after chemotherapy.