Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer’s disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3′,4′-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model. In BV2 microglial cells, 3′,4′-dihydroxyflavone successfully inhibited production of chemokines such as nitric oxide and prostaglandin E2 and proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in BV2 microglia. It also inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation. This indicates that the anti-inflammatory activities of 3′,4′-dihydroxyflavone might be related to suppression of the proinflammatory MAPK and NF-κB signaling pathways. Similar anti-neuroinflammatory activities of the compound were observed in the mouse model. These findings suggest that 3′,4′-dihydroxyflavone is a potential drug candidate for the treatment of microglia-related neuroinflammatory diseases.
Animals ; Central Nervous System ; Chemokines ; Cytokines ; Dinoprostone ; Huntington Disease ; Interleukin-1beta ; Interleukin-6 ; Mice* ; Microglia* ; Neurodegenerative Diseases ; Nitric Oxide ; Parkinson Disease ; Phosphorylation ; Protein Kinases ; Tumor Necrosis Factor-alpha

OBJECTIVES: The purpose of this study was to compare the efficacy of galantamine treatment, especially attention ability between patients with pure Alzheimer's disease (AD) and Mixed dementia (MD) during a 24-week trial. METHODS: A total of 40 patients were recruited for this 24-week study. The effect of galantamine on attention was measured using Seoul Computerized NeuroCognitive Function Test (SCNT) and frontal functions test of Seoul Neuropsychological Screening Battery (SNSB). Patients'activities of daily living using the Seoul-Activities of Daily Living (S-ADL) and the Seoul-Instrumental Activities of Daily Living (S-IADL) ; behavioral symptoms using the Korean version Neuropsychiatric Inventory (K-NPI) were measured at baseline and 24-week. RESULTS: 17 pure AD patients and 23 MD patients were analyzed in this study. Attention as measured by SCNT was not significantly different from baseline after 24 weeks of treatment in both groups. There was no significant difference between two groups in mean change from baseline in the SCNT, S-ADL, S-IADL and K-NPI scores at 24-week. CONCLUSION: Galantamine showed a therapeutic effect on cognition, activities of daily living, neuropsychiatric symptoms in pure AD and MD. Furthermore, Galantamine may specifically help to maintain attention and it may have positive effects on other cognitive and functional abilities.
Activities of Daily Living ; Alzheimer Disease ; Attention ; Behavioral Symptoms ; Cognition ; Dementia ; Galantamine ; Humans ; Mass Screening

OBJECTIVE: Depression is a very common symptom in people with mild cognitive impairment (MCI), a preclinical stage of Alzheimer's disease (AD), and in those with clinically evident AD. Moreover, MCI individuals with depression show a higher conversion rate to clinical AD than those without depression. This study aimed to elucidate the functional neuroanatomical substrate of depression in MCI. METHODS: Thirty-six patients were recruited from a University Hospital-based cohort; 18 of these subjects had MCI with depression (MCI_D); the remaining 18 subjects were age- and gender-matched, and had MCI with no depression (MCI_ND). For comparison, 16 cognitively normal (CN) elderly individuals were also included. All subjects underwent Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) scanning and regional cerebral glucose metabolism was compared among the three groups by a voxel-based method. The relationship between severity of depression, as measured by Hamilton Rating Scale for Depression (HRSD) scores, and glucose metabolism was also investigated. RESULTS: MCI_D showed lower glucose metabolism in the right superior frontal gyrus than MCI_ND. There was a significant negative correlation between HRSD score and glucose metabolism at the same frontal region for overall MCI subjects. When compared with CN, both MCI_D and MCI_ND showed decreased glucose metabolism in the precuneus, while MCI_D had, in addition, reduced metabolism in other diffuse brain regions. CONCLUSION: Given previous observations on depression in AD, our results suggest that functional disruption of the frontal region, known to be associated with primary or other secondary depression, underlies depression in preclinical AD as well as clinically evident AD.
Aged ; Alzheimer Disease ; Brain ; Depression ; Glucose ; Humans ; Mild Cognitive Impairment ; Positron-Emission Tomography

OBJECTIVES: The purpose of this study was to compare the efficacy between switching patients with Alzheimer's disease (AD) from galantamine or rivastigmine to donepezil because they were not responding adequately, and naive patients with AD who initiated therapy with donepezil. METHODS: A total of 108 patients were recruited for this 52-week study. The effect of donepezil on cognitive function was measured using Alzheimer's Disease Assessment Scale-cognitive subscale-preliminary Korean version (ADAS-cog-K). Patients' activities of daily living using Seoul-Activities of Daily Living (S-ADL) and the Seoul-Instrumental Activities of Daily Living (S-IADL);behavioral symptoms using the Korean version Neuropsychiatric Inventory (K-NPI) were measured at baseline, 13-weeks, 26-weeks, 39-weeks and 52-weeks. We defined the responsive patients to donepezil at those who showed a cognitive improvement or no change during the first six-month clinical trial. RESULTS: 86 naive patients and 22 switching patients were enrolled in the study. 74 patients completed the study and 34 discontinued their treatment before week 52. There was no significant difference between two patient groups in demographic data, baseline characteristics and dementia severity except duration of illness. The total ADAS-cog-K scores were not significantly different from baseline after 52 weeks of treatment in both groups. Both groups demonstrated deterioration of S-ADL and S-IADL at 52 weeks. The NPI scores did not significantly change in both groups. Based on the operational criteria, 61.6% of the naive group and 54.5% of the switching group were responders to donepezil. CONCLUSION: The switching group had similar levels of efficacy with the naive group who initiated therapy with donepezil. These results suggest that patients not responding adequately to rivastigmine or galantamine may improve or stabilize after switching to donepezil and prior medication does not effect donepezil's efficacy.

OBJECTIVES: The purpose of this study was to compare the efficacy of donepezil treatment between patients with pure Alzheimer's disease (AD) and Mixed dementia (MD) during a 12-month trial. METHODS: A total of 139 patients were recruited for this 52-week study. The effect of donepezil on cognitive function was measured using Alzheimer's Disease Assessment Scale-cognitive subscale-preliminary Korean version (ADAS-cog-K). Patients' activities of daily living using the Seoul-Instrumental Activities of Daily Living (S-IADL) and Seoul-Activities of Daily Living (S-ADL);behavioral symptoms using the Korean version Neuropsychiatric Inventory (K-NPI) were measured at baseline, 13-weeks, 26-weeks, 39-weeks and 52-weeks. We defined the responsive patients to donepezil at those who showed a cognitive improvement or no change during the first six-month clinical trial. RESULTS: 84 pure AD patients and 34 MD patients were available for intent-to-treat (ITT) last observation carried forward (LOCF) analysis. There was no significant difference between two groups in mean change from baseline in the total ADAS-cog-k, S-ADL, S-IADL and K-NPI scores at 52-week. Based on the operational criteria, 60.7% of pure AD patients and 58.8% of MD patients were responders to donepezil. CONCLUSION: MD patients had similar levels of efficacy with pure AD patients and donepezil was well tolerated in both groups. These results suggest that donepezil is an effective and well-tolerated treatment for MD patients as well as for pure AD patients.
Activities of Daily Living ; Alzheimer Disease ; Dementia ; Humans ; Indans ; Piperidines

OBJECTIVES: The purpose of this study was to compare the efficacy of donepezil treatment between patients with pure Alzheimer's disease (AD) and Mixed dementia (MD) during a 12-month trial. METHODS: A total of 139 patients were recruited for this 52-week study. The effect of donepezil on cognitive function was measured using Alzheimer's Disease Assessment Scale-cognitive subscale-preliminary Korean version (ADAS-cog-K). Patients' activities of daily living using the Seoul-Instrumental Activities of Daily Living (S-IADL) and Seoul-Activities of Daily Living (S-ADL);behavioral symptoms using the Korean version Neuropsychiatric Inventory (K-NPI) were measured at baseline, 13-weeks, 26-weeks, 39-weeks and 52-weeks. We defined the responsive patients to donepezil at those who showed a cognitive improvement or no change during the first six-month clinical trial. RESULTS: 84 pure AD patients and 34 MD patients were available for intent-to-treat (ITT) last observation carried forward (LOCF) analysis. There was no significant difference between two groups in mean change from baseline in the total ADAS-cog-k, S-ADL, S-IADL and K-NPI scores at 52-week. Based on the operational criteria, 60.7% of pure AD patients and 58.8% of MD patients were responders to donepezil. CONCLUSION: MD patients had similar levels of efficacy with pure AD patients and donepezil was well tolerated in both groups. These results suggest that donepezil is an effective and well-tolerated treatment for MD patients as well as for pure AD patients.
Activities of Daily Living ; Alzheimer Disease ; Dementia ; Humans ; Indans ; Piperidines

The aim of this study was to investigate whether stereotactic body radiotherapy (SBRT) can salvage gastric cancer patients with para-aortic lymph node (PALN) recurrence. From January 2003 to December 2006, 7 patients were treated for isolated PALN recurrence from gastric cancer after curative resection. Follow up durations ranged from 19 to 33 months (median; 26 months), and SBRT doses from 45 Gy to 51 Gy (median 48 Gy) in 3 fractions. Disease progression-free and overall survivals and toxicities were recorded. Response to treatment was assessed by computed tomography. Final patient outcomes were as follows: 2 were alive without evidence of disease, 3 remained alive with disease, and 2 patients died of disease. Five of 7 patients showed complete response and 2 patients partial response between 3 and 11 months after SBRT. Three-year overall and disease progression-free survival rates post-SBRT were 43% and 29%, respectively. No severe complication was detected during follow-up. Selected patients with isolated PALN recurrence can be salvaged by SBRT without severe complications.
Adult ; Aged ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*radiotherapy/surgery ; Radiosurgery ; Radiotherapy Dosage ; Recurrence ; Stomach Neoplasms/diagnosis/pathology/*surgery ; Survival Analysis

The aim of this study was to investigate whether stereotactic body radiotherapy (SBRT) can salvage gastric cancer patients with para-aortic lymph node (PALN) recurrence. From January 2003 to December 2006, 7 patients were treated for isolated PALN recurrence from gastric cancer after curative resection. Follow up durations ranged from 19 to 33 months (median; 26 months), and SBRT doses from 45 Gy to 51 Gy (median 48 Gy) in 3 fractions. Disease progression-free and overall survivals and toxicities were recorded. Response to treatment was assessed by computed tomography. Final patient outcomes were as follows: 2 were alive without evidence of disease, 3 remained alive with disease, and 2 patients died of disease. Five of 7 patients showed complete response and 2 patients partial response between 3 and 11 months after SBRT. Three-year overall and disease progression-free survival rates post-SBRT were 43% and 29%, respectively. No severe complication was detected during follow-up. Selected patients with isolated PALN recurrence can be salvaged by SBRT without severe complications.
Adult ; Aged ; Disease-Free Survival ; Female ; Humans ; Lymph Nodes/surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*radiotherapy/surgery ; Radiosurgery ; Radiotherapy Dosage ; Recurrence ; Stomach Neoplasms/diagnosis/pathology/*surgery ; Survival Analysis

The inhibitory Smad6 and Smad7 are responsible for cross-talk between TGF-beta/bone morphogenic protein (BMP) signaling and other cellular signaling pathways, as well as negative feedback on their own signaling functions. Although inhibitory Smads are induced by various stimuli, little is known about the stimuli that increase Smad6 transcription, in contrast to Smad7. Here we demonstrate that etoposide, which induces double strand breaks during DNA replication, significantly up-regulates the transcription of the Smad6 gene in CMT-93 mouse intestinal cells by increasing specific DNA binding proteins. In addition, endogenous inhibition of the Smad6 gene by RNAi interference led to transient accumulation of G1 phase cells and reduction in incorporation of bromodeoxyuridine (BrdU). These findings strongly suggest that Smad6 plays a distinct role in the signaling of etoposide-induced DNA damage.
Animals ; Base Sequence ; Cell Line ; DNA-Binding Proteins/metabolism ; Enterocytes/*cytology/drug effects/*metabolism ; Etoposide/*pharmacology ; G1 Phase/*drug effects ; Mice ; Molecular Sequence Data ; Promoter Regions, Genetic/genetics ; RNA, Small Interfering/metabolism ; S Phase/*drug effects ; Smad6 Protein/*genetics ; Transcriptional Activation/drug effects

PURPOSE: The purpose of this study was to explore the effects of the lavender fragrance on sleep and depression in women college students. METHOD: Forty-two women college students who complained of insomnia were studied during a four-week protocol(control treatment week, 60% lavender fragrance treatment week, washout week, 100% lavender fragrance treatment week). All subjects were in the department of nursing in "K" college and the study was a single blind repeated measurements experiment. For the duration of the study, weekly evaluations of sleep, patterns of sleep disturbance, severity of insomnia scale, self satisfaction with sleep, and severity of depression were performed. RESULT: Among sleep variables, length of time taken to fall asleep, severity of insomnia, and self satisfaction with sleep were improved for the 60%(p=.000, p=.000, p=.000) and 100%(p=.000, p=.000, p=.000) week while the severity of depression was improved only for the 100%(p=.002)week. CONCLUSION: According to the study results, it can be concluded that the lavender fragrance had a beneficial effect on insomnia and depression in women college students. Repeated studies are needed to confirm effective proportions of lavender oil and carrier oil for insomnia and depression.
Students/*psychology ; Sleep Initiation and Maintenance Disorders/*therapy ; *Lavandula ; Humans ; Female ; Depression/*therapy ; *Aromatherapy ; Adult