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1.
Medicine (Baltimore) ; 101(51): e32282, 2022 Dec 23.
Article in English | MEDLINE | ID: mdl-36595753

ABSTRACT

BACKGROUND: Since 4 major diseases and geriatric diseases require consistent management, individuals with any of these diseases cannot live alone and need caregivers' assistance. Given these characteristics, an integrative medical service model for 4 major diseases and geriatric diseases was developed in Korea, currently. Dementia, one of the typical geriatric diseases, requires caregivers' assistance from the beginning because of its enormous burden. Thus, it is necessary to provide an integrative medical service that can improve the quality of life (QoL) for both patients and caregivers. Therefore, this study aims to collect various feedback by applying an integrative medical service, which was developed to improve the QoL in patients with dementia and their caregivers, to a single case, and to modify and improve the integrative medical service model based on the results. METHOD/DESIGN: The integrative medical service program, which was developed to improve the QoL in patients with dementia and their caregivers in Korea, will be used for a patient-caregiver pair. This is an observational study with quantitative and qualitative feedback from various viewpoints. The program will be conducted in 8 sessions (twice a week, within 120 minutes). The patient will receive both Western and Korean medicine, and an integrative service will be provided to improve cognitive rehabilitation and QoL. Feedback collected at each session will be reflected on the program of the subsequent session. RESULTS: This study will then modify and improve the program with feedback and provide integrative medical services to a patient with dementia and caregiver. DISCUSSION: Patients with dementia need a program that would help them maintain cognitive function, and caregivers need a program that would improve their QoL by reducing the caregiving burden. This study is unique because the developed program is performed after modification based on feedback from the previous session. Accordingly, the patient and caregiver can check which program is the most satisfactory and helpful in improving their QoL. We expect that this study can modify the integrative medical service model to the optimized patient-based model. This study can also be used as basic data for a clinical pathway development study that applies the modified model to medical institutes.


Subject(s)
Dementia , Quality of Life , Humans , Aged , Quality of Life/psychology , Caregivers/psychology , Dementia/psychology , Cognition
2.
Biochem Biophys Res Commun ; 482(4): 1088-1094, 2017 Jan 22.
Article in English | MEDLINE | ID: mdl-27914807

ABSTRACT

Leucine-rich repeat kinase (LRRK2), a major causal gene of Parkinson's disease (PD), functions as a kinase. The most prevalent mutation of LRRK2 is G2019S. It exhibits increased kinase activity compared to the wildtype LRRK2. Previous studies have shown that LRRK2 can phosphorylate p53 at T304 and T377 of threonine-X-arginine (TXR) motif in neurons. Reduction of LRRK2 expression or inhibition of LRRK2 kinase activity has been shown to be able to alleviate LPS-induced neuroinflammation in microglia cells. In this study, we found that LRRK2 could also phosphorylate p53 in microglia model BV2 cells. Transfection of BV2 with phosphomimetic p53 T304/377D significantly increased the secretion of pro-inflammatory cytokine TNFα compared to BV2 transfected with p53 wild type after LPS treatment. In addition, conditioned media from these transfected cells increased the death of dopaminergic neuronal SN4741 cells. Moreover, such neurotoxic effect was rescued by co-treatment with the conditioned media and etanercept, a TNFα blocking antibody. Furthermore, TNFα secretion was significantly increased in primary microglia derived from G2019S transgenic mice treated with LPS compared to that in cells derived from their littermates. These results suggest that LRRK2 kinase activity in microglia can contribute to neuroinflammation in PD via phosphorylating p53 at T304 and T377 site.


Subject(s)
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/metabolism , Microglia/metabolism , Tumor Necrosis Factor-alpha/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Cell Survival , Culture Media, Conditioned/chemistry , Disease Models, Animal , Etanercept/chemistry , Inflammation , Lipopolysaccharides/chemistry , Mice , Mice, Transgenic , Neurons/metabolism , Parkinson Disease/metabolism , Phosphorylation
3.
J Pharmacopuncture ; 16(2): 28-32, 2013 Jun.
Article in English | MEDLINE | ID: mdl-25780665

ABSTRACT

OBJECTIVE: This study was performed to analyze the single-dose toxicity of D-amino acid oxidase (DAAO) extracts. METHODS: All experiments were conducted at the Korea Testing & Research Institute (KTR), an institution authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP). Sprague-Dawley rats were chosen for the pilot study. Doses of DAAO extracts, 0.1 to 0.3 cc, were administered to the experimental group, and the same doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. RESULTS: In all 4 groups, no deaths occurred, and the LD50 of DAAO extracts administered by IV was over 0.3 ml/kg. No significant changes in the weight between the control group and the experimental group were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ, the results showed no significant differences in any organs or tissues. CONCLUSION: The above findings suggest that treatment with D-amino acid oxidase extracts is relatively safe. Further studies on this subject should be conducted to yield more concrete evidence.

4.
Toxicol Lett ; 199(3): 239-46, 2010 Dec 15.
Article in English | MEDLINE | ID: mdl-20851755

ABSTRACT

Paraquat produces dopaminergic pathologies of Parkinson's disease, in which cyclooxygenase-2 (COX-2) is implicated. However, it is unclear whether paraquat induces toxicity within dopaminergic neurons through COX-2. To address this, human neuroblastoma SH-SY5Y cells were treated with paraquat and then the involving mechanism of COX-2 was investigated. We initially examined the involvement of COX-2 in paraquat-induced toxicity. Data suggest that COX-2 is implicated in paraquat-induced reduction of viability in SY5Y cells. Then, to confirm the presence of COX-2 in SY5Y cells, we examined COX-2 mRNA and protein levels, which are regulated by NF-κB. Data indicate that paraquat activates NF-κB and up-regulates COX-2. We then checked quinone-bound proteins as quinones produced by COX-2 bind to intracellular proteins. Paraquat obviously forms quinone-bound proteins, in particular, quinone-bound DJ-1 and this formation is attenuated by meloxicam. Finally, we investigated antioxidant system including nuclear factor erythroid-related factor 2 (Nrf2), gamma glutamylcysteine synthetase (γGCS), and glutathione (GSH) as DJ-1 is linked to Nrf2 and Nrf2 regulates γGCS expression and γGCS is a GSH synthesis enzyme. Paraquat decreases protein levels of Nrf2 and γGCS and intracellular GSH level and these decreases are alleviated by meloxicam. Therefore, collectively, our data indicate that paraquat induces COX-2 implicated toxicity in SY5Y cells. In conclusion, current findings support the idea that paraquat might produce toxicity in dopaminergic neurons through COX-2.


Subject(s)
Cyclooxygenase 2/physiology , Herbicides/toxicity , Paraquat/toxicity , Cell Line, Tumor , Cell Survival/drug effects , Cyclooxygenase 2/analysis , Cyclooxygenase 2/genetics , Glutamate-Cysteine Ligase/metabolism , Glutathione/analysis , Humans , Intracellular Signaling Peptides and Proteins/analysis , Intracellular Signaling Peptides and Proteins/metabolism , L-Lactate Dehydrogenase/metabolism , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Neuroblastoma/pathology , Oncogene Proteins/analysis , Oncogene Proteins/metabolism , Protein Deglycase DJ-1 , Quinones/metabolism
5.
Korean J Physiol Pharmacol ; 13(4): 273-9, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19885010

ABSTRACT

The accumulation of beta-amyloid (Abeta) aggregates is a characteristic of Alzheimer's disease (AD). Furthermore, these aggregates have neurotoxic effects on cells, and thus, molecules that inhibit Abeta aggregate formation could be valuable therapeutics for AD. It is well known that aggregation of Abeta depends on its hydrophobicity, and thus, in order to increase the hydrophilicity of Abeta, we considered using citrate, an anionic surfactant with three carboxylic acid groups. We hypothesized that citrate could reduce hydrophobicity and increase hydrophilicity of Abeta(1-40) molecules via hydrophilic/electrostatic interactions. We found that citrate significantly inhibited Abeta(1-40) aggregation and significantly protected SH-SY5Y cell line against Abeta(1-40) aggregates-induced neurotoxicity. In details, we examined the effects of citrate on Abeta(1-40) aggregation and on Abeta(1-40) aggregates-induced cytotoxicity, cell viability, and apoptosis. Th-T assays showed that citrate significantly inhibited Abeta(1-40) aggregation in a concentration-dependent manner (Th-T intensity: from 91.3% in 0.01 mM citrate to 82.1% in 1.0 mM citrate vs. 100.0% in Abeta(1-40) alone). In cytotoxicity and viability assays, citrate reduced the toxicity of Abeta(1-40) in a concentration-dependent manner, in which the cytotoxicity decreased from 107.5 to 102.3% as compared with Abeta(1-40) aggregates alone treated cells (127.3%) and the cell viability increased from 84.6 to 93.8% as compared with the Abeta(1-40) aggregates alone treated cells (65.3%). Furthermore, Hoechst 33342 staining showed that citrate (1.0 mM) suppressed Abeta(1-40) aggregates-induced apoptosis in the cells. This study suggests that citrate can inhibit Abeta(1-40) aggregation and protect neurons from the apoptotic effects of Abeta(1-40) aggregates. Accordingly, our findings suggest that citrate administration should be viewed as a novel neuroprotective strategy for AD.

6.
Toxicol Lett ; 191(2-3): 203-10, 2009 Dec 15.
Article in English | MEDLINE | ID: mdl-19735704

ABSTRACT

Epidemiologic and laboratory studies suggest that paraquat can be an environmental etiologic factor in Parkinson's disease (PD). One mechanism by which paraquat may mediate cell death of dopaminergic neurons is by inducing endoplasmic reticulum (ER) stress, as suggested in a recent report. In this study, we further investigated this linkage by examining ER stress cascades. To this aim, human neuroblastoma cells (SH-SY5Y cells) were treated with paraquat and the signaling cascades through which ER stress results in apoptosis were examined. Then, it was examined whether ER stress is produced by paraquat. Paraquat increased ER stress biomarker proteins, glucose-regulated protein 78 (GRP78), ER degradation-enhancing alpha-mannosidae-like protein (EDEM), and C/EBP homologous protein (CHOP). Then, it was investigated which ER stress cascades are affected by paraquat. Paraquat activated inositol-requiring enzyme 1 (IRE1), apoptosis signal regulating kinase 1 (ASK1), and c-jun kinase (JNK). Also, paraquat activated calpain and caspase 3, but did not affect the levels of intracellular calcium and the activity of caspase 12. Finally, apoptotic DNA damage by paraquat was investigated and this damage was attenuated by salubrinal (ER stress inhibitor), thioredoxin (ASK1 inhibitor) and SP600125 (JNK inhibitor). Therefore, current data indicate that paraquat activates the IRE1/ASK1/JNK cascade associated with apoptosis in SY5Y cells.


Subject(s)
Apoptosis/drug effects , Endoribonucleases/biosynthesis , Herbicides/toxicity , JNK Mitogen-Activated Protein Kinases/biosynthesis , MAP Kinase Kinase Kinase 5/biosynthesis , Membrane Proteins/biosynthesis , Paraquat/toxicity , Protein Serine-Threonine Kinases/biosynthesis , Blotting, Western , Calcium Signaling/physiology , Caspases/metabolism , Cell Line, Tumor , Coloring Agents , DNA Damage , Endoplasmic Reticulum Chaperone BiP , Endoribonucleases/genetics , Formazans/metabolism , Heat-Shock Proteins/biosynthesis , Humans , JNK Mitogen-Activated Protein Kinases/genetics , MAP Kinase Kinase Kinase 5/genetics , Membrane Proteins/genetics , Phosphorylation , Protein Serine-Threonine Kinases/genetics , Signal Transduction/drug effects , Transcription Factor CHOP/biosynthesis , Trypan Blue
7.
Pharmazie ; 64(11): 760-4, 2009 Nov.
Article in English | MEDLINE | ID: mdl-20099523

ABSTRACT

Beta-amyloid (Abeta)-induced neurotoxicity is considered to be mediated through the formation of reactive oxygen species (ROS). In this study, the protective effects of Poria cocos water extract (PCW) against Abeta1-42-induced cell death were investigated using rat pheochromocytoma (PC12) cells. Exposure of PC12 cells to the Abeta1-42 (20 microM) for 48h resulted in neuronal cell death, whereas pretreatment with PCW at the concentration range of 5-125 microg/ml reduced Abeta1-42-induced cell death. In addition, PC12 cells treated with Abeta1-42 exhibited increased accumulation of intracellular oxidative damages and underwent apoptotic death as determined by characteristic morphological alterations and positive in situ terminal end-labeling (TUNEL staining). However, PCW attenuated Abeta1-42-induced cytotoxicity, apoptotic features, and accumulation of intracellular oxidative damage. Moreover, PCW (5 to 125 microg/ml) decreased expression of apoptotic protein Bax and activity of caspase-3, but enhanced expression of anti-apoptotic protein Bcl-2. These results suggest that PCW may protect cells through suppressing the oxidative stress and the apoptosis induced by Abeta1-42, implying that PCW may be potential natural agents for Alzheimer's diseases.


Subject(s)
Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/toxicity , Antioxidants/pharmacology , Apoptosis/drug effects , Neuroprotective Agents , Poria/chemistry , Animals , Caspase 3/metabolism , Cell Death , Enzyme Activation/drug effects , In Situ Nick-End Labeling , L-Lactate Dehydrogenase/metabolism , Oxidative Stress/drug effects , PC12 Cells , Plant Extracts/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Tetrazolium Salts , Up-Regulation/drug effects , bcl-2-Associated X Protein/metabolism
8.
J Neuroimaging ; 18(4): 451-3, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18318795

ABSTRACT

The dissection of the intracranial vertebral artery (VAD) is a common cause of young age brain stem stroke. VAD can be detected by conventional angiography, but there is yet no agreement on the most effective tool to use for the detection of VAD. Here, we report a patient with VAD, who was diagnosed with an intimal flap within the left vertebral artery by the magnetic resonance angiography (MRA) source images. Transcranial Doppler (TCD) showed a reversed flow in the basilar artery. After 4 months, TCD and transcranial color-coded Doppler (TCCD) confirmed a normal anterograde flow of the vertebro-basilar arteries.


Subject(s)
Basilar Artery , Brain Stem Infarctions/diagnosis , Diffusion Magnetic Resonance Imaging , Magnetic Resonance Angiography , Medulla Oblongata/blood supply , Ultrasonography, Doppler, Color , Ultrasonography, Doppler, Transcranial , Vertebral Artery Dissection/diagnosis , Collateral Circulation/physiology , Dominance, Cerebral/physiology , Follow-Up Studies , Humans , Male , Manipulation, Chiropractic/adverse effects , Middle Aged , Regional Blood Flow/physiology , Vertebrobasilar Insufficiency/diagnosis
9.
Molecules ; 12(5): 1125-35, 2007 May 24.
Article in English | MEDLINE | ID: mdl-17873846

ABSTRACT

A simple synthesis of sulfonamides 4-22 as novel histone deacetylase (HDAC) inhibitors is described. The key synthetic strategies involve N-sulfonylation of L-proline benzyl ester hydrochloride (2) and coupling reaction of N-sulfonyl chloride 3 with amines in high yields. It was found that several compounds showed good cellular potency with the most potent compound 20 exhibiting an IC50 = 2.8 microM in vitro.


Subject(s)
Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Histone Deacetylase Inhibitors , Sulfonamides/chemical synthesis , Sulfonamides/pharmacology , Cell Line, Tumor , Chromatography, Thin Layer , Drug Screening Assays, Antitumor , Humans , Magnetic Resonance Spectroscopy , Spectrometry, Mass, Electrospray Ionization , Spectroscopy, Fourier Transform Infrared
10.
Molecules ; 12(5): 1147-52, 2007 May 25.
Article in English | MEDLINE | ID: mdl-17873848

ABSTRACT

During our investigation of the neuroprotective activity of Platycodi radix we found that an aqueous extract of this folk medicine exhibited significant protection against glutamate-induced toxicity in primary cultured rat cortical cells. In order to clarify the neuroprotective mechanism(s) of this observed effect, activity-guided isolation was performed to seek and identify active fractions and components. By such fractionation, four known triterpene saponin compounds--platycodins A, C and D and deapioplatycodin D--were isolated from the n-butanol fraction. Among these four compounds, platycodin A exhibited significant neuroprotective activities against glutamate-induced toxicity, exhibiting cell viability of about 50%, at concentrations ranging from 0.1 microM to 10 microM. Therefore, the neuroprotective effect of Platycodi radix might be due to the inhibition of glutamate-induced toxicity by the saponin compounds it contains.


Subject(s)
Campanulaceae/chemistry , Neuroprotective Agents/pharmacology , Saponins/pharmacology , Triterpenes/pharmacology , Animals , Cells, Cultured , Chromatography, Gel , Chromatography, Ion Exchange , Gas Chromatography-Mass Spectrometry , Rats , Spectrophotometry, Ultraviolet
11.
Molecules ; 12(4): 815-20, 2007 Apr 20.
Article in English | MEDLINE | ID: mdl-17851433

ABSTRACT

A sulfur compound, bis(4-hydroxybenzyl)sulfide (1) was isolated from the root extract of Pleuropterus ciliinervis. Its structure was elucidated using NMR spectroscopic techniques and mass spectrometric analysis. Compound 1 showed potent inhibitory activity in a histone deacetylase (HDAC) enzyme assay. It also exhibited growth inhibitory activity on five human tumor cell lines and more sensitive inhibitory activity on the MDA-MB-231 breast tumor cell line.


Subject(s)
Antineoplastic Agents/chemistry , Enzyme Inhibitors/chemical synthesis , Histone Deacetylases/chemistry , Plant Extracts/metabolism , Sulfides/chemistry , Sulfur Compounds/chemistry , Sulfur/chemistry , Antineoplastic Agents/chemical synthesis , Cell Line, Tumor , Drug Screening Assays, Antitumor , Enzyme Inhibitors/chemistry , Histone Deacetylase Inhibitors , Humans , Mass Spectrometry/methods , Models, Chemical , Plant Roots/metabolism , Sensitivity and Specificity , Tetrazolium Salts/chemistry , Thiazoles/chemistry
12.
Bioorg Med Chem Lett ; 17(17): 4753-5, 2007 Sep 01.
Article in English | MEDLINE | ID: mdl-17662606

ABSTRACT

The major constituents from the fruits of Maclura pomifera are the prenylated isoflavones, osajin (1) and pomiferin (2). Their structures were elucidated using NMR spectroscopic techniques and mass spectrometric analysis. Compound 2 showed potential inhibitory activity in histone deacetylase (HDAC) enzyme assay. It also exhibited growth inhibitory activity on five human tumor cell lines and more sensitive inhibitory activity on the HCT-15 colon tumor cell line. Further structure-activity relationships of position 3 on ring B from aromatic ring will be reported in due course.


Subject(s)
Benzopyrans/pharmacology , Enzyme Inhibitors/pharmacology , Histone Deacetylase Inhibitors , Plant Extracts/isolation & purification , Benzopyrans/isolation & purification , Cell Line, Tumor , Drug Screening Assays, Antitumor , Enzyme Inhibitors/isolation & purification , Fruit , Humans , Isoflavones , Maclura/metabolism , Magnetic Resonance Spectroscopy , Structure-Activity Relationship
13.
Parasitol Res ; 101(1): 237-41, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17211658

ABSTRACT

New stilbene glycoside, piceid-(1-->6)-beta-D -glucopyranoside (compound 2, Fig. 1), was isolated from the MeOH extract of the leaves of Parthenocissus tricuspidata (Vitaceae) together with four known compounds, piceid (compound 1, Fig. 1), resveratrol (compound 3, Fig. 1), longistylin A (compound 4, Fig. 1), and longistylin C (compound 5, Fig. 1). Their structures were determined spectroscopically, particularly by 2D nuclear magnetic resonance (NMR) spectroscopic and chemical analysis. The antiplasmodial activity of isolated compounds were determined in vitro against a chloroquine-sensitive strain of Plasmodium falciparum (D10). Among the compounds isolated, piceid-(1-->6)-beta-D-glucopyranoside (2) had the most potential inhibition, with inhibitory concentration (IC(50)) values of 5.3 microM. To our knowledge, antiplasmodial activity of functional group position of stilbene is now being reported for the first time in this study. The result shows that the 3, 4'-position in stilbenes might play an essential role in antiplasmodial activity.


Subject(s)
Plasmodium falciparum/drug effects , Stilbenes/chemistry , Stilbenes/pharmacology , Vitaceae/chemistry , Animals , Antimalarials/chemistry , Antimalarials/pharmacology , Molecular Structure
14.
J Clin Neurosci ; 13(2): 245-8, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16434197

ABSTRACT

It is well known that motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) of the motor cortex are facilitated by voluntary muscle contraction. We evaluated the effects of imagination of movements on MEP latencies of agonist and antagonist muscles in the hand using TMS. Twenty-two healthy volunteers were studied. TMS delivered at rest and while imagining tonic abduction of the right thumb. MEPs were recorded in response to magnetic stimulation over the scalp and cervical spine (C7-T1), and central motor conduction times (CMCT) were calculated. MEPs were recorded from right abductor pollicis brevis muscle (APB) and adductor pollicis muscle (AP) simultaneously. Imagination of abduction resulted in a shortened latency of MEPs in the APB muscle, and a prolonged latency in the AP muscle. But the imagination caused no significant change in the latency of MEPs elicited by stimulation over the cervical spine. The changes of the CMCT may account for these latency changes with imagination of movement. These findings indicate that imagination of thumb abduction facilitates motoneurons of agonist muscle and has an inhibitory effect on those of antagonist muscle (reciprocal inhibition).


Subject(s)
Movement/physiology , Thumb/diagnostic imaging , Transcranial Magnetic Stimulation , Adult , Cervical Vertebrae , Electric Stimulation , Electromyography , Evoked Potentials, Motor/physiology , Female , Humans , Imagination/physiology , Male , Neural Conduction/physiology , Radiography , Thumb/physiology
15.
J Clin Neurol ; 1(1): 104-6, 2005 Apr.
Article in English | MEDLINE | ID: mdl-20396479

ABSTRACT

The involvement of the nervous system in Kikuchi's disease (KD) is rare. Although some reports of meningeal involvement in KD were described in the literature from Japan, it has rarely been reported in Korea. A 23-year-old man presented with severe headache, fever, and vomiting. Cerebrospinal fluid (CSF) analysis revealed an opening pressure 300 mmH(2)O, WBC 283/mm(3), glucose 44 mg/dl and protein 86 mg/dl. Multiple tender lymph nodes on the left anterior neck were found on the 9(th) day of his hospital stay. The lymph node biopsy disclosed histopathologic features typical of KD. We report a patient with KD accompanied by aseptic meningitis, emphasizing the importance of recognizing this disorder in diagnosing patients with meningitis.

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