The effects of capsaicin (CAP), a transient receptor potential vanilloid subtype 1 (TRPV1) agonist, were determined on nigrostriatal dopamine (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). The results showed that TRPV1 activation by CAP rescued nigrostriatal DA neurons, enhanced striatal DA functions and improved behavioral recovery in MPTP-treated mice. CAP neuroprotection was associated with reduced expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) and reactive oxygen species/reactive nitrogen species from activated microglia-derived NADPH oxidase, inducible nitric oxide synthase or reactive astrocyte-derived myeloidperoxidase. These beneficial effects of CAP were reversed by treatment with the TRPV1 antagonists capsazepine and iodo-resiniferatoxin, indicating TRPV1 involvement. This study demonstrates that TRPV1 activation by CAP protects nigrostriatal DA neurons via inhibition of glial activation-mediated oxidative stress and neuroinflammation in the MPTP mouse model of PD. These results suggest that CAP and its analogs may be beneficial therapeutic agents for the treatment of PD and other neurodegenerative disorders that are associated with neuroinflammation and glial activation-derived oxidative damage.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine* ; Animals ; Capsaicin* ; Cytokines ; Dopamine* ; Dopaminergic Neurons* ; Mice ; NADPH Oxidase ; Necrosis ; Neurodegenerative Diseases ; Neurons ; Neuroprotection ; Nitric Oxide Synthase Type II ; Nitrogen ; Oxidative Stress* ; Oxygen ; Parkinson Disease*

Amyloid fibril formation has been implicated in the pathogenesis of neurodegenerative diseases. Fibrillation generates numerous conformers. Presumably, the conformers may possess specific biological properties, thus providing a biochemical framework for strains of prions. However, the precise relationship between various fibril conformers and their pathogenic functions has not been determined because of limited accessibility to adequate amounts of fibrils from tissue samples. α-Synuclein is one such protein, and it has been implicated in Parkinson disease. Using a technique known as protein misfolding cyclic amplification, originally developed for amplifying prions, we established a procedure through which the amplification of α-synuclein fibrils is possible. With a trace amount of seeds, we succeeded in amplifying α-synuclein fibrils. The replication of the seeds was faithful in terms of conformation even after multiple rounds of cyclic amplification. Moreover, two transgenic mouse strains each representing a distinct synucleinopathy were used to investigate different conformers by using this technique. The amplified α-synuclein fibrils derived from the tissue extracts of these two strains led to the production of two different fibril conformers with distinct proteinase K digestion profiles. Together, our results demonstrated that a trace amount of α-synuclein fibrils in tissue extracts could be amplified with their conformations conserved. This procedure should be useful in amplifying α-synuclein fibrils from the brains and body fluids of patients afflicted with synucleinopathies and may serve as a potential diagnostic tool for Parkinson disease and other synucleinopathies.
Amyloid ; Animals ; Body Fluids ; Brain ; Digestion ; Endopeptidase K ; Humans ; Mice ; Mice, Transgenic ; Neurodegenerative Diseases ; Parkinson Disease ; Prions ; Tissue Extracts

The cannabinoid (CB2) receptor type 2 has been proposed to prevent the degeneration of dopamine neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. However, the mechanisms underlying CB2 receptor-mediated neuroprotection in MPTP mice have not been elucidated. The mechanisms underlying CB2 receptor-mediated neuroprotection of dopamine neurons in the substantia nigra (SN) were evaluated in the MPTP mouse model of Parkinson's disease (PD) by immunohistochemical staining (tyrosine hydroxylase, macrophage Ag complex-1, glial fibrillary acidic protein, myeloperoxidase (MPO), and CD3 and CD68), real-time PCR and a fluorescein isothiocyanate-labeled albumin assay. Treatment with the selective CB2 receptor agonist JWH-133 (10 μg kg⁻¹, intraperitoneal (i.p.)) prevented MPTP-induced degeneration of dopamine neurons in the SN and of their fibers in the striatum. This JWH-133-mediated neuroprotection was associated with the suppression of blood-brain barrier (BBB) damage, astroglial MPO expression, infiltration of peripheral immune cells and production of inducible nitric oxide synthase, proinflammatory cytokines and chemokines by activated microglia. The effects of JWH-133 were mimicked by the non-selective cannabinoid receptor WIN55,212 (10 μg kg⁻¹, i.p.). The observed neuroprotection and inhibition of glial-mediated neurotoxic events were reversed upon treatment with the selective CB2 receptor antagonist AM630, confirming the involvement of the CB2 receptor. Our results suggest that targeting the cannabinoid system may be beneficial for the treatment of neurodegenerative diseases, such as PD, that are associated with glial activation, BBB disruption and peripheral immune cell infiltration.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine* ; Animals ; Blood-Brain Barrier ; Chemokines ; Cytokines ; Dopamine* ; Dopaminergic Neurons* ; Fluorescein ; Glial Fibrillary Acidic Protein ; Macrophages ; Mice ; Microglia ; Neurodegenerative Diseases ; Neuroprotection ; Nitric Oxide Synthase Type II ; Parkinson Disease* ; Peroxidase ; Real-Time Polymerase Chain Reaction ; Receptor, Cannabinoid, CB2* ; Receptors, Cannabinoid ; Substantia Nigra

Eradication of Helicobacter pylori using first-line therapy is becoming less effective. Subjects who had been treated for H. pylori infection were prospectively enrolled through an on-line database registry from October 2010 to December 2012. Demographic data, detection methods, treatment indication, regimens, durations, compliance, adverse events, and eradication results for H. pylori infection were collected. Data of 3,700 patients from 34 hospitals were analyzed. The overall eradication rate of the first-line therapy was 73.0%. Eradication failure was significantly associated with old age, concomitant medication, and comorbidity. Regional differences in eradication rates were observed. The most common first-line therapy was proton pump inhibitor-based triple therapy (standard triple therapy, STT) for 7 days (86.8%). The eradication rates varied with regimens, being 73% in STT, 81.8% in bismuth-based quadruple therapy, 100% in sequential therapy, and 90.3% in concomitant therapy. The eradication rate in treatment-naïve patients was higher than that in patients previously treated for H. pylori infection (73.8% vs. 58.5%, P < 0.001). The overall eradication rate for second-line therapy was 84.3%. There was no statistical difference in eradication rates among various regimens. H. pylori eradication rate using STT is decreasing in Korea and has become sub-optimal, suggesting the need for alternative regimens to improve the efficacy of first-line therapy for H. pylori infection.
Adult ; Age Factors ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Databases, Factual ; Drug Therapy, Combination ; Female ; Helicobacter Infections/*drug therapy/microbiology ; Helicobacter pylori/isolation & purification ; Humans ; Internet ; Logistic Models ; Male ; Middle Aged ; Prospective Studies ; Proton Pump Inhibitors/*therapeutic use ; Registries ; Republic of Korea ; Treatment Outcome

Eradication of Helicobacter pylori using first-line therapy is becoming less effective. Subjects who had been treated for H. pylori infection were prospectively enrolled through an on-line database registry from October 2010 to December 2012. Demographic data, detection methods, treatment indication, regimens, durations, compliance, adverse events, and eradication results for H. pylori infection were collected. Data of 3,700 patients from 34 hospitals were analyzed. The overall eradication rate of the first-line therapy was 73.0%. Eradication failure was significantly associated with old age, concomitant medication, and comorbidity. Regional differences in eradication rates were observed. The most common first-line therapy was proton pump inhibitor-based triple therapy (standard triple therapy, STT) for 7 days (86.8%). The eradication rates varied with regimens, being 73% in STT, 81.8% in bismuth-based quadruple therapy, 100% in sequential therapy, and 90.3% in concomitant therapy. The eradication rate in treatment-naïve patients was higher than that in patients previously treated for H. pylori infection (73.8% vs. 58.5%, P < 0.001). The overall eradication rate for second-line therapy was 84.3%. There was no statistical difference in eradication rates among various regimens. H. pylori eradication rate using STT is decreasing in Korea and has become sub-optimal, suggesting the need for alternative regimens to improve the efficacy of first-line therapy for H. pylori infection.
Adult ; Age Factors ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Databases, Factual ; Drug Therapy, Combination ; Female ; Helicobacter Infections/*drug therapy/microbiology ; Helicobacter pylori/isolation & purification ; Humans ; Internet ; Logistic Models ; Male ; Middle Aged ; Prospective Studies ; Proton Pump Inhibitors/*therapeutic use ; Registries ; Republic of Korea ; Treatment Outcome

PURPOSE: Mutations in BRCA genes are the main cause of hereditary breast cancer in Korea. The aim of this study was to investigate the characteristics of breast cancers involving BRCA1 (BRCA1 group) and BRCA2 (BRCA2 group) mutations. METHODS: We retrospectively reviewed the medical records of patients with BRCA1 (BRCA1 group) or BRCA2 (BRCA2 group) mutation positive breast cancer from multiple centers and compared the data to that of the Korean Breast Cancer Society registry (registry group). RESULTS: The patients of the BRCA1 group were diagnosed at a younger age (median age, 37 years) and had tumors of higher histological (61.3% with histological grade 3) and nuclear (37.5% with nuclear grade 3) grade than those of the registry group. In addition, the frequency of ductal carcinoma in situ in the BRCA1 group was lower (3.7%) than in the registry group, and the BRCA1 group were more likely to be triple-negative breast cancer (61.3%). Patients in the BRCA2 group were also younger at diagnosis (mean age, 41 years) and were more likely to have involvement of the axillary node than the registry group (45.5% vs. 33.5%, p=0.002). The BRCA1 and BRCA2 groups did not show a correlation between tumor size and axillary node involvement. CONCLUSION: We report the characteristics of BRCA mutation positive breast cancer patients in the Korean population through multicenter data and nation-wide breast cancer registry study. However, BRCA-mutated breast cancers appear highly complex, and further research on their molecular basis is needed in Korea.
Breast Neoplasms* ; Breast* ; Carcinoma, Intraductal, Noninfiltrating ; Diagnosis ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Korea ; Medical Records ; Retrospective Studies ; Triple Negative Breast Neoplasms

Recent studies suggest that the intracoronary administration of bone marrow (BM)-derived mesenchymal stem cells (MSCs) may improve left ventricular function in patients with acute myocardial infarction (AMI). However, there is still argumentative for the safety and efficacy of MSCs in the AMI setting. We thus performed a randomized pilot study to investigate the safety and efficacy of MSCs in patients with AMI. Eighty patients with AMI after successful reperfusion therapy were randomly assigned and received an intracoronary administration of autologous BM-derived MSCs into the infarct related artery at 1 month. During follow-up period, 58 patients completed the trial. The primary endpoint was changes in left ventricular ejection fraction (LVEF) by single-photon emission computed tomography (SPECT) at 6 month. We also evaluated treatment-related adverse events. The absolute improvement in the LVEF by SPECT at 6 month was greater in the BM-derived MSCs group than in the control group (5.9%+/-8.5% vs 1.6%+/-7.0%; P=0.037). There was no treatment-related toxicity during intracoronary administration of MSCs. No significant adverse cardiovascular events occurred during follow-up. In conclusion, the intracoronary infusion of human BM-derived MSCs at 1 month is tolerable and safe with modest improvement in LVEF at 6-month follow-up by SPECT. (ClinicalTrials.gov registration number: NCT01392105)
Adult ; Aged ; Bone Marrow Cells/cytology ; Cell- and Tissue-Based Therapy/*adverse effects ; Echocardiography ; Female ; Heart/physiopathology ; Humans ; Male ; Mesenchymal Stem Cell Transplantation/*adverse effects ; Mesenchymal Stromal Cells/*cytology ; Middle Aged ; Myocardial Infarction/*therapy ; Pilot Projects ; Stroke Volume ; Tomography, Emission-Computed, Single-Photon ; Transplantation, Autologous ; Treatment Outcome ; Ventricular Function, Left ; Young Adult

BACKGROUND/AIMS: The role of Helicobacter pylori eradication in patients with functional dyspepsia (FD) is still uncertain. We originally planned a randomized clinical study to observe dyspeptic symptoms after H. pylori eradication therapy. However, we failed to complete the study; therefore, we analyzed the factors that affected the failure of the study. METHODS: Interviews and questionnaire surveys were conducted to analyze the factors that induced early termination from the study. RESULTS: Many patients were screened by gastroenterologists at 11 tertiary referral hospitals between July 2009 and August 2010; however, only 4 patients met the enrollment criteria. Most patients who visited our clinics had been experiencing FD symptoms for less than 6 months or were already taking medication. They also demanded to continue taking medications and using other drugs. Only 3 of the 4 patients signed informed consent. CONCLUSIONS: The application of the current Rome III criteria to FD is difficult to evaluate in Korean patients with dyspeptic symptoms because of the early medical evaluation. Most Korean patients who were diagnosed with FD by the Rome III criteria did not overcome their fear of being unable to use rescue medications during the study period.
Dyspepsia ; Helicobacter pylori ; Humans ; Rome ; Tertiary Care Centers ; Surveys and Questionnaires

PURPOSE: The objective of this study was to evaluate the change in the practice patterns for managing hereditary breast and ovarian cancer (HBOC) among Korean physicians after the Korean Hereditary Breast Cancer (KOHBRA) study. METHODS: The first survey was performed from July to August 2007, at the initiation of the KOHBRA study, and the follow-up survey was conducted from July to December 2009. Members of the Korean Breast Cancer Society were invited to participate in the study by e-mail. The 2009 survey was conducted with a self-administered questionnaire concerning HBOC management and was identical to the previous questionnaire. RESULTS: According to the 2009 survey, most physicians (60.0%) tended to draw a pedigree (48.0% in 2007 survey). The rate of genetic test recommendations for patients at risk for HBOC was higher in the 2009 survey (84.0%) than that in the 2007 survey (64.0%). Physicians tended to select a BRCA genetic testing candidate more appropriately than in the previous survey (42.4% answered right in 2007 survey; 74.4% in 2009 survey). Fifteen of 25 participants (60.0%) provided genetic counseling before their patients underwent a genetic test, which was higher than that (40.0%) in the 2007 survey. According to the 2009 survey, half of the genetic counseling was being conducted by KOHBRA study research nurses; whereas most of the genetic counseling was conducted by physicians in 2007. CONCLUSION: The KOHBRA study has played an important role in the appropriate selection of candidates for genetic testing. However, more effort should be placed on improving the pre-test genetic counseling rate.
Breast ; Breast Neoplasms ; Electronic Mail ; Follow-Up Studies ; Genetic Counseling ; Genetic Testing ; Humans ; Korea ; Neoplastic Syndromes, Hereditary ; Ovarian Neoplasms ; Pedigree ; Physician's Practice Patterns ; Surveys and Questionnaires

Stem cells provide an important means for regenerative medicine due to the capacity to generate multiple types of differentiated cells and at the same time to maintain self-renewal. To identify the therapeutic effect of the transplantation of neural stem cells, differentiation and migration capacity of the neural stem cells that were isolated from E14 rat embryo and maintained in culture were examined after transplantation to the striatum of the quinolinic acid (QA)-induced Huntington's disease rat model. in vitro co-culture of the neural stem cells with the mixture of primary neurons and astrocytes promoted the maturation and the synapse formation of neuronal progenies of neural stem cells. Following the implantation, the neural stem cells survived, differentiated, and migrated in the damaged striatum region, exhibiting immunoreactivities against nestin, Tuj-1, GFAP, GAD(67) and synapsin 1 to a varying degree. These data provide clear evidence supporting that the neural stem cells isolated from the rat embryo and maintained in the primary culture have a multiple capacity to differentiate into neurons or glial cells both in vitro and in vivo.
Animals ; Astrocytes ; Brain ; Coculture Techniques ; Embryonic Structures ; Huntington Disease ; Intermediate Filament Proteins ; Nerve Tissue Proteins ; Neural Stem Cells ; Neuroglia ; Neurons ; Quinolinic Acid ; Rats ; Regenerative Medicine ; Synapses ; Transplants