BACKGROUND/OBJECTIVES: Reactive oxygen species (ROS) formation is closely related to miconazole-induced heart dysfunction. Although rhamnetin has antioxidant effects, it remained unknown whether it can protect against miconazole-induced cardiomyocyte apoptosis. Thus, we investigated the effects of rhamnetin on miconazole-stimulated H9c2 cell apoptosis. MATERIALS/METHODS: Cell morphology was observed by inverted microscope and cell viability was determined using a WelCount(TM) cell proliferation assay kit. Miconazole-induced ROS production was evaluated by fluorescence-activated cell sorting with 6-carboxy-2',7'-dichlorofluoroscein diacetate (H2DCF-DA) stain. Immunoblot analysis was used to determine apurinic/apyrimidinic endonuclease 1 (APE/Ref-1) and cleaved cysteine-aspartic protease (caspase) 3 expression. NADPH oxidase levels were measured using real-time polymerase chain reaction. RESULTS: Miconazole (3 and 10 microM) induced abnormal morphological changes and cell death in H9c2 cells. Rhamnetin enhanced the viability of miconazole (3 microM)-treated cells in a dose-dependent manner. Rhamnetin (1 and 3 microM) treatment downregulated cleaved caspase 3 and upregulated APE/Ref-1 expression in miconazole-stimulated cells. Additionally, rhamnetin significantly reduced ROS generation. CONCLUSIONS: Our data suggest that rhamnetin may have cytoprotective effects in miconazole-stimulated H9c2 cardiomyocytes via ROS inhibition. This effect most likely occurs through the upregulation of APE/Ref-1 and attenuation of hydrogen peroxide levels.
Antioxidants ; Apoptosis ; Caspase 3 ; Cell Death ; Cell Proliferation ; Cell Survival ; Flow Cytometry ; Heart ; Hydrogen Peroxide ; Miconazole ; Myocytes, Cardiac ; NADPH Oxidase ; Reactive Oxygen Species ; Real-Time Polymerase Chain Reaction ; Up-Regulation

Luminespib (AUY922), a heat shock proteins 90 inhibitor, has anti-neoplastic and antitumor effects. However, it is not clear whether AUY922 affects events in vascular diseases. We investigated the effects of AUY922 on the platelet-derived growth factor (PDGF)-BB-stimulated proliferation and migration of vascular smooth muscle cells (VSMC). VSMC viability was detected using the XTT (2,3-bis-(2-methoxy- 4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reagent. To detect the attenuating effects of AUY922 on PDGF-BB-induced VSMCs migration in vitro, we performed the Boyden chamber and scratch wound healing assays. To identify AUY922- mediated changes in the signaling pathway, the phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) 1/2 was analyzed by immunoblotting. The inhibitory effects of AUY922 on migration and proliferation ex vivo were tested using an aortic ring assay. AUY922 was not cytotoxic at concentrations up to 5 nM. PDGF-BB-induced VSMC proliferation, migration, and sprout outgrowth were significantly decreased by AUY922 in a dose-dependent manner. AUY922 significantly reduced the PDGF-BB-stimulated phosphorylation of Akt and ERK1/2. Furthermore, PD98059 (a selective ERK1/2 inhibitor) and LY294002 (a selective Akt inhibitor) decreased VSMC migration and proliferation by inhibiting phosphorylation of Akt and ERK1/2. Greater attenuation of PDGF-BB-induced cell viability and migration was observed upon treatment with PD98059 or LY294002 in combination with AUY922. AUY922 showed anti-proliferation and anti-migration effects towards PDGF-BBinduced VSMCs by regulating the phosphorylation of ERK1/2 and Akt. Thus, AUY922 is a candidate for the treatment of atherosclerosis and restenosis.

Luminespib (AUY922), a heat shock proteins 90 inhibitor, has anti-neoplastic and antitumor effects. However, it is not clear whether AUY922 affects events in vascular diseases. We investigated the effects of AUY922 on the platelet-derived growth factor (PDGF)-BB-stimulated proliferation and migration of vascular smooth muscle cells (VSMC). VSMC viability was detected using the XTT (2,3-bis-(2-methoxy- 4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reagent. To detect the attenuating effects of AUY922 on PDGF-BB-induced VSMCs migration in vitro, we performed the Boyden chamber and scratch wound healing assays. To identify AUY922- mediated changes in the signaling pathway, the phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) 1/2 was analyzed by immunoblotting. The inhibitory effects of AUY922 on migration and proliferation ex vivo were tested using an aortic ring assay. AUY922 was not cytotoxic at concentrations up to 5 nM. PDGF-BB-induced VSMC proliferation, migration, and sprout outgrowth were significantly decreased by AUY922 in a dose-dependent manner. AUY922 significantly reduced the PDGF-BB-stimulated phosphorylation of Akt and ERK1/2. Furthermore, PD98059 (a selective ERK1/2 inhibitor) and LY294002 (a selective Akt inhibitor) decreased VSMC migration and proliferation by inhibiting phosphorylation of Akt and ERK1/2. Greater attenuation of PDGF-BB-induced cell viability and migration was observed upon treatment with PD98059 or LY294002 in combination with AUY922. AUY922 showed anti-proliferation and anti-migration effects towards PDGF-BBinduced VSMCs by regulating the phosphorylation of ERK1/2 and Akt. Thus, AUY922 is a candidate for the treatment of atherosclerosis and restenosis.

Ocular neuromyotonia (ONM) is an episodic involuntary contraction of one or more extraocular muscles, resulting from spontaneous neural discharges of ocular motor nerves. Previous radiation therapy to pituitary or other juxtasellar tumor and vascular compressions are the most common reported causes of ONM. We report one unique case of ONM involving the abducens nerve without any other organic brain lesion and prior radiation therapy.
Abducens Nerve ; Brain ; Isaacs Syndrome* ; Muscles

BACKGROUND/OBJECTIVES: Yacon (Samallanthus sonchifolius), a common edible plant grown throughout the world, is well known for its antidiabetic properties. It is also known to have several other pharmacological properties including anti-inflammatory, anti-oxidant, anti-allergic, and anti-cancer effects. To date, the effect of yacon on gliomas has not been studied. In this study, we investigated the effects of yacon on the migration and proliferation of C6 glioma cells stimulated by fetal bovine serum (FBS). MATERIALS/METHODS: Cell growth and proliferation were determined by evaluating cell viability using an EZ-Cytox Cell Viability Assay Kit. FBS-induced migration of C6 glioma cells was evaluated by performing the scratch wound healing assay and the Boyden chamber assay. We also used western blot analysis to determine the expression levels of extracellular signal-regulated kinase 1/2 (ERK1/2), a major regulator of migration and proliferation of glioma cells. Matrix metallopeptidase (MMP) 9 and TIMP-1 levels were measured by performing reverse transcription PCR. RESULTS: Yacon (300 microg/mL) reduced both the FBS-induced proliferation of C6 glioma cells and the dose-dependent migration of the FBS-stimulated C6 cells. FBS-stimulated C6 glioma cells treated with yacon (200 and 300 microg/mL) showed reduced phosphorylation of ERK1/2 and inhibition of MMP 9 expression compared to those shown by the untreated FBS-stimulated C6 cells. In contrast, yacon (200 and 300 microg/mL) induced TIMP-1 expression. CONCLUSIONS: On the basis of these results, we suggest that yacon may exert an anti-cancer effect on FBS-stimulated C6 glioma cells by inhibiting their proliferation and migration. The most likely mechanism for this is down-regulation of ERK1/2 and MMP9 and up-regulation of TIMP-1 expression levels.
Blotting, Western ; Cell Proliferation* ; Cell Survival ; Down-Regulation ; Ethanol* ; Glioma* ; Phosphorylation ; Phosphotransferases ; Plants, Edible ; Polymerase Chain Reaction ; Reverse Transcription ; Tissue Inhibitor of Metalloproteinase-1 ; Up-Regulation ; Wound Healing

STUDY DESIGN: Observational. PURPOSE: To develop a simple and comprehensive grading system for cervical discs that precisely, consistently and meaningfully presents radiologic and morphologic data. OVERVIEW OF LITERATURE: The Thompson grading system is commonly used to classify the severity of degenerative lumbar discs on magnetic resonance imaging (MRI). Inherent differences in the morphological and physiological characteristics of cervical discs have hindered development of precise classification systems. Other grading systems have been developed for degenerating cervical discs, but their versatility and feasibility in the clinical setting is suboptimal. METHODS: MRIs of 46 human cervical discs were de-identified and displayed in PowerPoint format. Each slide depicted a single disc with a normal (grade 0) disc displayed in the top right corner for reference. The presentation was given to 25 physicians comprising attending spine surgeons, spine fellows, orthopaedic residents, and two attending musculoskeletal radiologists. The grading system included Grade 0 (normal height compared to C2-3, mid cleft still visible), grade 1 (dark disc, normal height), grade 2 (collapsed disc, few osteophytes), and grade 3 (collapsed disc, many osteophytes). The ease of use of the system was gauged in the participants and the interobserver reliability was calculated. RESULTS: The intraclass correlation coefficient for interobserver reliability was 0.87, and 0.94 for intraobserver reliability, indicating excellent reliability. Ninety-five percent and 85 percent of the clinicians judged the grading system to be clinically feasible and useful in daily practice, respectively. CONCLUSIONS: The grading system is easy to use, has excellent reliability, and can be used for precise and consistent clinician communication.
Classification ; Humans ; Intervertebral Disc Degeneration* ; Intervertebral Disc* ; Magnetic Resonance Imaging* ; Spine

PURPOSE: To identify cognitive effects of lamotrigine (LTG) compared with valproate (VPA) in epilepsy patients after 1 year of treatment. METHODS: Cognitive tests and subjective complaints of 22 patients with LTG monotherapy (50-200 mg/day) were retrospectively compared with those of 22 patients with VPA monotherapy (500-1300 mg/day) at 1 year of medication. RESULTS: LTG group did not show any significant difference in the performance of cognitive tests compared with VPA group. The incidence of cognitive complaints between two drugs were also not different. Both groups showed a better performance of list learning and Trail Making Test type A after antiepileptic drug medication. CONCLUSION: The impact of LTG and VPA monotherapy on cognitive functioning is similar. Both drugs may not be harmful or rather slightly beneficial for cognitive functions.
Cognition ; Epilepsy* ; Humans ; Incidence ; Learning ; Retrospective Studies ; Trail Making Test ; Valproic Acid*

BACKGROUND: Impaired verbal fluency in Alzheimer's disease (AD) has been well documented. Furthermore, crosssectional studies suggest that semantic fluency is disproportionately impaired relative to phonemic fluency in AD. The aim of this study was to determine the ability of fluency measures as follow-up screening tool for mild to moderate AD. METHODS: Participants were recruited from AD patients in mild to moderate stages. We annually evaluated semantic (animal, supermarket) and phonemic (giyeok, siot, ieung) fluency and tested other extensive neuropsychological measures for two years. RESULTS: A total of 33 AD patients were included at baseline and 1-year follow-up, who were aged 70.18+/-5.97 years at baseline. Eleven patients completed a 2-year follow-up. Phonemic fluency total score was not significantly changed during the study period. However, semantic fluency total score tended to decline annually, and significantly declined at 2-year follow-up compared to baseline. In addition, difference score (semantic fluency minus phonemic fluency) was significantly decreased at every follow-up compared to previous year. In Pearson correlation analyses between changes of verbal fluency and other neuropsychological measures, changes of semantic fluency appeared to be significantly correlated with neuropsychological measures much more than changes of phonemic fluency. CONCLUSIONS: Significant longitudinal declines in semantic fluency compared to phonemic fluency seem to be consistent with previous cross-sectional studies. These patterns of changes in verbal fluency were observed even at an interval of one year follow-up in our study. The verbal fluency might be useful follow-up screening test for mild to moderate AD in the memory clinic setting.
Aged ; Alzheimer Disease ; Follow-Up Studies ; Humans ; Longitudinal Studies ; Mass Screening ; Memory ; Semantics

Changes in the expression profiles of specific proteins leads to serious human diseases, including colitis. The proteomic changes related to colitis and the differential expression between tuberculous (TC) and ulcerative colitis (UC) in colon tissue from colitis patients has not been defined. We therefore performed a proteomic analysis of human TC and UC mucosal tissue. Total protein was obtained from the colon mucosal tissue of normal, TC, and UC patients, and resolved by 2-dimensional electrophoresis (2-DE). The results were analyzed with PDQuest using silver staining. We used matrix-assisted laser desorption ionization time-of-flight/time-of-flight spectrometry (MALDI TOF/TOF) to identify proteins differentially expressed in TC and UC. Of the over 1,000 proteins isolated, three in TC tissue and two in UC tissue displayed altered expression when compared to normal tissue. Moreover, two proteins were differentially expressed in a comparative analysis between TC and UC. These were identified as mutant beta-actin, alpha-enolase and Charcot-Leyden crystal protein. In particular, the expression of alpha-enolase was significantly greater in TC compared with normal tissue, but decreased in comparison to UC, implying that alpha-enolase may represent a biomarker for differential diagnosis of TC and UC. This study therefore provides a valuable resource for the molecular and diagnostic analysis of human colitis.
Actins ; Colitis ; Colitis, Ulcerative ; Colon ; Diagnosis, Differential ; Electrophoresis ; Glycoproteins ; Humans ; Lysophospholipase ; Mucous Membrane ; Phosphopyruvate Hydratase ; Proteins ; Proteomics ; Silver Staining ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Spectrum Analysis ; Ulcer

BACKGROUND/OBJECTIVES: One of the mechanisms considered to be prevalent in the development of Alzheimer's disease (AD) is hyper-stimulation of microglia. Black chokeberry (Aronia melanocapa L.) is widely used to treat diabetes and atherosclerosis, and is known to exert anti-oxidant and anti-inflammatory effects; however, its neuroprotective effects have not been elucidated thus far. MATERIALS/METHODS: We undertook to assess the anti-inflammatory effect of the ethanolic extract of black chokeberry friut (BCE) in BV2 cells, and evaluate its neuroprotective effect in the lipopolysaccharide (LPS)-induced mouse model of AD. RESULTS: Following stimulation of BV2 cells by LPS, exposure to BCE significantly reduced the generation of nitric oxide as well as mRNA levels of numerous inflammatory factors such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α). In addition, AD was induced in a mouse model by intraperitoneal injection of LPS (250 µg/kg), subsequent to which we investigated the neuroprotective effects of BCE (50 mg/kg) on brain damage. We observed that BCE significantly reduced tissue damage in the hippocampus by downregulating iNOS, COX-2, and TNF-α levels. We further identified the quinic acids in BCE using liquid chromatography-mass spectrometry (LCMS). Furthermore, we confirmed the neuroprotective effect of BCE and quinic acid on amyloid beta-induced cell death in rat hippocampal primary neurons. CONCLUSIONS: Our findings suggest that black chokeberry has protective effects against the development of AD.
Alzheimer Disease ; Amyloid ; Animals ; Atherosclerosis ; Brain ; Cell Death ; Cyclooxygenase 2 ; Ethanol ; Hippocampus ; Inflammation ; Injections, Intraperitoneal ; Interleukin-1beta ; Mice ; Mice, Inbred ICR ; Microglia ; Neurons ; Neuroprotective Agents ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Phytochemicals ; Quinic Acid ; Rats ; RNA, Messenger ; Spectrum Analysis ; Tumor Necrosis Factor-alpha