• Radiation Oncology Journal
• /
• v.38 no.1
• /
• pp.35-43
• /
• 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.

• The Korean Journal of Physiology and Pharmacology
• /
• v.19 no.3
• /
• pp.219-228
• /
• 2015

Excessive microglial activation and subsequent neuroinflammation lead to synaptic loss and dysfunction as well as neuronal cell death, which are involved in the pathogenesis and progression of several neurodegenerative diseases. Thus, the regulation of microglial activation has been evaluated as effective therapeutic strategies. Although dieckol (DEK), one of the phlorotannins isolated from marine brown alga Ecklonia cava, has been previously reported to inhibit microglial activation, the molecular mechanism is still unclear. Therefore, we investigated here molecular mechanism of DEK via extracellular signal-regulated kinase (ERK), Akt and nicotinamide adenine dinuclelotide phosphate (NADPH) oxidase-mediated pathways. In addition, the neuroprotective mechanism of DEK was investigated in microglia-mediated neurotoxicity models such as neuron-microglia co-culture and microglial conditioned media system. Our results demonstrated that treatment of anti-oxidant DEK potently suppressed phosphorylation of ERK in lipopolysaccharide (LPS, $1{\mu}g/ml$)-stimulated BV-2 microglia. In addition, DEK markedly attenuated Akt phosphorylation and increased expression of $gp91^{phox}$, which is the catalytic component of NADPH oxidase complex responsible for microglial reactive oxygen species (ROS) generation. Finally, DEK significantly attenuated neuronal cell death that is induced by treatment of microglial conditioned media containing neurotoxic secretary molecules. These neuroprotective effects of DEK were also confirmed in a neuron-microglia co-culture system using enhanced green fluorescent protein (EGFP)-transfected B35 neuroblastoma cell line. Taken together, these results suggest that DEK suppresses excessive microglial activation and microglia-mediated neuronal cell death via downregulation of ERK, Akt and NADPH oxidase-mediated pathways.

• Progress in Medical Physics
• /
• v.26 no.2
• /
• pp.72-78
• /
• 2015

Organic solvents are known toxic effects like vertigo, behavioral obstacle, distracting, and peripheral neuropathy in neuron areas. However, there have been few studies how neurotoxic solvents-exposed workers are affected by the cognitive load of preceding working memory tasks. Therefore, we used fMRI as to measure the neural correlates of working memory impairment in occupational workers who had from chronic exposure to organic solvent. Twenty-nine solvent-exposed workers were included in this study. Each participant concluded the verbal N-back tasks (1- and 2-back) during the fMRI acquisition. Within-group analyses showed fronto-parietal networks were active in each condition. Direct comparisons between 1- and 2-back showed higher activation during the 2-back than 1-back. We found that increased activation of these regions at lower task demand is associated with increased cost of implementing.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.43 no.2
• /
• pp.224-230
• /
• 2014

Marine algae have long been recognized as a health and beauty food, based on its anti-tumor, anti-inflammatory and anti-obesity activities. In this study, methanol extracts were prepared from 10 different phaeophyta, after which DPPH radical scavenging and cytoprotective activities of HT-22 cells against ${\beta}$-amyloid protein ($A{\beta}$), which has neurotoxic effects, were investigated. In DPPH experiments, Ecklonia cava and Ishige okamurai showed strong ROS scavenging activities, whereas eight other phaeophyta including Petalonia binghamiae (P. bin) showed weak ROS scavenging activities. To validate the cytoprotective effects of 10 different phaeophyta in $A{\beta}$-induced HT-22 cells, protein expression levels of APP, BACE1, iNOS, phosphorylated ERK1/2, phosphorylated p38 and phosphorylated JNK1/2 were determined along with MTT assay. In the MTT assay, P. bin showed the best effective cytoprotective activity at a concentrations of $25{\mu}g/mL$, whereas Sargassum confusum, Colpomenia sinuosa, Myelophycus simplex, and Sargassum hemiphyllum showed potential. Determination of protein expression levels related to $A{\beta}$-induced neurotoxicity in the five selected phaeophyta showed that P. bin inhibited BACE1 and iNOS expression in $A{\beta}$-induced HT-22 cells. These results indicate that the cytoprotective effects of P. bin are mediated by suppressing the pathways involving $A{\beta}$-induced ERK and p38 activation.

• Journal of Life Science
• /
• v.21 no.6
• /
• pp.796-804
• /
• 2011

Microglia are central nervous system (CNS)-resident professional macrophages that function as the principal immune cells responding to pathological stimulations in the CNS. Activation of microglia, induced by various pathogens, protects neurons and maintains homeostasis in the CNS, but severe activation causes inflammatory responses secreting various neurotoxic molecules such as nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) and pro-inflammatory cytokines. Allium fistulosum, a member of the onion family, is mainly cultivated for consumption, as well as medicinal use in Oriental medicine. It has been reported that A. fistulosum has various biological effects such as anti-oxidant, anti-platelet aggregation, anti-fungus and anti-cholesterol synthesis, however there has been no research about the anti-inflammatory effects of A. fistulosum extracts. In this study, it was undertaken to explore the functions of A. fistulosum as a suppressor of neuronal inflammation by using BV2 microglia cells. As a result, it was found that four kinds of extracts of A. fistulosum effectively reduced the expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) at both mRNA and protein levels, and also attenuated pro-inflammatory cytokines such as tumor necrosis alpha (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$) and interleukin-6 (IL-6) at the mRNA level in BV2 stimulated by lipopolysaccharide (LPS). In addition, the extracts of A. fistulosum attenuated the release of NO markedly, as well as resulting in slight decreases of TNF-${\alpha}$ and IL-6 production, the effects of which were most significant when treated with ethyl alcohol extract from the whole A. fistulosum. In conclusion, the data indicated that the anti-inflammatory actions of A. fistulosum against BV2 microglia cells is through the down-regulation of iNOS, COX2 and pro-inflammatory cytokines such as TNF-${\alpha}$ and IL-6, and these effects are expected to help in the protection of nerve tissues by suppressions of neuronal inflammation in various neurodegenerative diseases.

• Journal of Environmental Health Sciences
• /
• v.37 no.2
• /
• pp.102-112
• /
• 2011

Objectives: The purpose of this study is to analyze the effects of chronic exposure by welders to manganese (Mn) through an analysis of the degree of brain activity in different activities such as cognition and motor activities using the neuroimaging technique of functional magnetic resonance imaging (fMRI). The neurotoxic effect that Mn has on the brain was examined as well as changes in the neuro-network in motor areas, and the usefulness of fMRI was evaluated as a tool to determine changes in brain function from occupational exposure to Mn. Methods: A survey was carried out from July 2010 to October 2010 targeting by means of a questionnaire 160 workers from the shipbuilding and other manufacturing industries. Among them, 14 welders with more than ten years of job-related exposure to Mn were recruited on a voluntary basis as an exposure group, and 13 workers from other manufacturing industries with corresponding gender and age were recruited as a control group. A questionnaire survey, a blood test, and an fMRI test were carried out with the study group as target. Results: Of 27 fMRI targets, blood Mn concentration of the exposure group was significantly higher than that of the control group (p<0.001), and Pallidal Index (PI) of the welder group was also significantly higher than that of the control group (p<0.001). As a result of the survey, the score of the exposure group in self-awareness of abnormal nerve symptoms and abnormal musculoskeletal symptoms was higher than those of the control group, and there was a significant difference between the two groups (p<0.05, respectively). In the correlation between PI and the results of blood tests, the correlation coefficient with blood Mn concentration was 0.893, revealing a significant amount of correlation (p<0.001). As for brain activity area within the control group, the right and the left areas of the superior frontal cortex showed significant activity, and the right area of superior parietal cortex, the left area of occipital cortex and cerebellum showed significant activity. Unlike the control group, the exposure group showed significant activity selectively on the right area of premotor cortex, at the center of supplementary motor area, and on the left side of superior temporal cortex. In the comparison of brain activity areas between the two groups, the exposure group showed a significantly higher activation state than did the control group in such areas as the right and the left superior parietal cortex, superior temporal cortex, and cerebellum including superior frontal cortex and the right area of premotor cortex. However, in nowhere did the control group show a more activated area than did the exposure group. Conclusions: Chronic exposure to Mn increased brain activity during implementation of hand motor tasks. In an identical task, activation increased in the premotor cortex, superior temporal cortex, and supplementary motor area. It was also discovered that brain activity increase in the frontal area and occipital area was more pronounced in the exposure group than in the control group. This result suggests that chronic exposure to Mn in the work environment affects brain activation neuro-networks.

• Korean Journal of Psychosomatic Medicine
• /
• v.30 no.2
• /
• pp.73-79
• /
• 2022

Objectives : Suicide is a global social problem. Social burden caused by suicide is gradually increasing. Various efforts have been made to prevent suicide. Lifestyle changes to western style, especially diet changes, have increased the risk for suicide. Therefore, in this study, we discussed diet as an adjuvant treatment for suicide. Methods : In this review, we summarized the biochemical mechanism of suicide, and diet as a risk factor for suicide and diet as a protective factor through a web search. Results : In this study, biochemical mechanisms for suicide were reviewed and diet as a risk factor and diet as a protective factor for suicide were investigated. It was confirmed that neurotoxic effects such as oxidative stress and inflammation in the neural system could increase the risk of suicide. Based on results of previous studies on the relationship between suicide and diet, it was found that heavy use of alcohol, coffee, carbonated soft drink, and fast food were risk factors for suicide. Protective factors for suicide included antioxidants such as vitamin C, carotene, and anti-inflammatory agents such as omega-3 fatty acids found in seafood in large amounts. Conclusions : The only treatment for suicide is prevention. In this context, effectiveness, accessibility, and safety are important for preventing for suicide. Antioxidants and anti-inflammatory agents that are relatively safe and readily available to the public could be effective adjuvant treatments to decrease the risk of suicide. In addition, it is necessary to educate the public on reducing diets that could increase the risk of suicide