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1.  Angiographic and Clinical Factors Related with Good Functional Outcome after Mechanical Thrombectomy in Acute Cerebral Artery Occlusion 
The aim of this study is to investigate good prognostic factors for an acute occlusion of a major cerebral artery using mechanical thrombectomy.
Between January 2013 to December 2014, 37 consecutive patients with acute occlusion of a major cerebral artery treated by mechanical thrombectomy with stent retrievers were conducted. We analyzed clinical and angiographic factors retrospectively. The collateral flow and the result of recanalization were sorted by grading systems. Outcome was assessed by National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at 90 days. We compared the various parameters between good and poor angiographic and clinical results.
Twenty seven patients demonstrated good recanalization [Thrombolysis in Cerebral Infarction (TICI) 2b or 3] after thrombectomy. At the 90-day follow up, 19 patients had good (mRS, 0-2), 14 had moderate (3-4) and four had poor outcomes (5-6). The mRS of older patients (≥75 years) were poor than younger patients. Early recanalization, high Thrombolysis in Myocardial Infarction risk score, and low baseline NIHSS were closely related to 90-day mRS, whereas high TICI was related to both mRS and the decrease in the NIHSS.
NIHSS decreased markedly only when recanalization was successful. A good mRS was related to low initial NIHSS, good collateral, and early successful recanalization.
PMCID: PMC4630348  PMID: 26539260
Acute cerebral artery occlusion; Functional outcome; Mechanical recanalization; Prognostic factor; Stent retriever
2.  Endovascular Treatment in Ruptured Middle Cerebral Artery Dissection Preservation of Arterial Continuity 
Rupture of spontaneous dissecting aneurysms of the middle cerebral artery (MCA) is rare and its etiology remains obscure, although the risk of rebleeding is greater than with saccular aneurysms. Most reports concerning the treatment of a ruptured dissecting aneurysm of the anterior circulation involve surgical trapping or wrapping. Here, we report on a case of an MCA dissecting rupture treated with endovascular procedures. A 22-year-old female presented with sudden stuporous mental change following severe headache and left side hemiparesis. A computed tomography scan showed a diffuse subarachnoid hemorrhage and diffusion MR showed diffusion restriction at the right putamen and internal capsule. A 3-hour follow-up digital subtraction angiography (DSA) showed a dissecting aneurysm, which was not seen on an initial DSA. A stent assisted coil embolization was performed and double stents were applied to achieve flow diversion effects. A small remnant area of the dissecting aneurysm had disappeared at 60-day and was not observed on 12-month follow-up DSA.
PMCID: PMC4495084  PMID: 26157690
Dissecting aneurysm; Middle cerebral artery; Flow diversion; Stent assisted coil embolization
3.  Lifespan extension and increased resistance to environmental stressors by N-Acetyl-L-Cysteine in Caenorhabditis elegans 
Clinics  2015;70(5):380-386.
This study was performed to determine the effect of N-acetyl-L-cysteine, a modified sulfur-containing amino acid that acts as a strong cellular antioxidant, on the response to environmental stressors and on aging in C. elegans.
The survival of worms under oxidative stress conditions induced by paraquat was evaluated with and without in vivo N-acetyl-L-cysteine treatment. The effect of N-acetyl-L-cysteine on the response to other environmental stressors, including heat stress and ultraviolet irradiation (UV), was also monitored. To investigate the effect on aging, we examined changes in lifespan, fertility, and expression of age-related biomarkers in C. elegans after N-acetyl-L-cysteine treatment.
Dietary N-acetyl-L-cysteine supplementation significantly increased resistance to oxidative stress, heat stress, and UV irradiation in C. elegans. In addition, N-acetyl-L-cysteine supplementation significantly extended both the mean and maximum lifespan of C. elegans. The mean lifespan was extended by up to 30.5% with 5 mM N-acetyl-L-cysteine treatment, and the maximum lifespan was increased by 8 days. N-acetyl-L-cysteine supplementation also increased the total number of progeny produced and extended the gravid period of C. elegans. The green fluorescent protein reporter assay revealed that expression of the stress-responsive genes, sod-3 and hsp-16.2, increased significantly following N-acetyl-L-cysteine treatment.
N-acetyl-L-cysteine supplementation confers a longevity phenotype in C. elegans, possibly through increased resistance to environmental stressors.
PMCID: PMC4449467  PMID: 26039957
N-acetyl-L-cysteine; C. elegans; Stress response; Lifespan; Fertility
4.  Acanthopanax sessiliflorus stem confers increased resistance to environmental stresses and lifespan extension in Caenorhabditis elegans 
Nutrition Research and Practice  2014;8(5):526-532.
Acanthopanax sessiliflorus is a native Korean plant and used as traditional medicine or an ingredient in many Korean foods. The free radical theory of aging suggests that cellular oxidative stress caused by free radicals is the main cause of aging. Free radicals can be removed by cellular anti-oxidants.
Here, we examined the anti-oxidant activity of Acanthopanax sessiliflorus extract both in vitro and in vivo. Survival of nematode C. elegans under stress conditions was also compared between control and Acanthopanax sessiliflorus extract-treated groups. Then, anti-aging effect of Acanthopanax sessiliflorus extract was monitored in C. elegans.
Stem extract significantly reduced oxidative DNA damage in lymphocyte, which was not observed by leaves or root extract. Survival of C. elegans under oxidative-stress conditions was significantly enhanced by Acanthopanax sessiliflorus stem extract. In addition, Acanthopanax sessiliflorus stem increased resistance to other environmental stresses, including heat shock and ultraviolet irradiation. Treatment with Acanthopanax sessiliflorus stem extract significantly extended both mean and maximum lifespan in C. elegans. However, fertility was not affected by Acanthopanax sessiliflorus stem.
Different parts of Acanthopanax sessiliflorus have different bioactivities and stem extract have strong anti-oxidant activity in both rat lymphocytes and C. elegans, and conferred a longevity phenotype without reduced reproduction in C. elegans, which provides conclusive evidence to support the free radical theory of aging.
PMCID: PMC4198965  PMID: 25324932
Acanthopanax sessiliflorus; Caenorhabditis elegans; lifespan; stress response; fertility
5.  Optimized Scheduling Technique of Null Subcarriers for Peak Power Control in 3GPP LTE Downlink 
The Scientific World Journal  2014;2014:279217.
Orthogonal frequency division multiple access (OFDMA) is a key multiple access technique for the long term evolution (LTE) downlink. However, high peak-to-average power ratio (PAPR) can cause the degradation of power efficiency. The well-known PAPR reduction technique, dummy sequence insertion (DSI), can be a realistic solution because of its structural simplicity. However, the large usage of subcarriers for the dummy sequences may decrease the transmitted data rate in the DSI scheme. In this paper, a novel DSI scheme is applied to the LTE system. Firstly, we obtain the null subcarriers in single-input single-output (SISO) and multiple-input multiple-output (MIMO) systems, respectively; then, optimized dummy sequences are inserted into the obtained null subcarrier. Simulation results show that Walsh-Hadamard transform (WHT) sequence is the best for the dummy sequence and the ratio of 16 to 20 for the WHT and randomly generated sequences has the maximum PAPR reduction performance. The number of near optimal iteration is derived to prevent exhausted iterations. It is also shown that there is no bit error rate (BER) degradation with the proposed technique in LTE downlink system.
PMCID: PMC4030578  PMID: 24883376
6.  Critical Use of Balloon Angioplasty after Recanalization Failure with Retrievable Stent in Acute Cerebral Artery Occlusion 
Sudden major cerebral artery occlusion often resists recanalization with currently available techniques or can results in massive symptomatic intracranial hemorrhage (sICH) after thrombolytic therapy. The purpose of this study was to examine mechanical recanalization with a retrievable self-expanding stent and balloon in acute intracranial artery occlusions.
Twenty-eight consecutive patients with acute intracranial artery occlusions were treated with a Solitaire retrievable stent. Balloon angioplasty was added if successful recanalization was not achieved after stent retrieval. The angiographic outcome was assessed by Thrombolysis in Cerebral Infarction (TICI) and the clinical outcomes were assessed by the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS).
At baseline, mean age was 69.4 years and mean initial NIHSS score was 12.5. A recanalization to TICI 2 or 3 was achieved in 24 patients (85%) after stent retrieval. Successful recanalization was achieved after additional balloon angioplasty in 4 patients. At 90-day follow-up, 24 patients (85%) had a NIHSS improvement of ≥4 and 17 patients (60%) had a good outcome (mRS ≤2). Although there was sICH, there was one death associated with the procedure.
Mechanical thromboembolectomy with a retrievable stent followed by additional balloon angioplasty is a safe and effective first-line therapy for acute intracranial artery occlusions especially in case of unsuccessful recanalization after stent thrombectomy.
PMCID: PMC3611063  PMID: 23560170
Acute cerebral artery occlusion; Mechanical recanalization; Retrievable stent; Balloon angioplasty
7.  Oxidative Stress and Longevity in C.elegans as Mediated by SKN-1 
Aging cell  2009;8(3):258-269.
Oxidative stress has been hypothesized to play a role in normal aging. The SKN-1 transcription factor regulates the response to oxidative stress and also is necessary for intestinal development in Caenorhabditis elegans. Using transcriptome analysis, we found that oxidative stress induces almost a thousand genes, including the antioxidant and heat-shock responses, as well as genes responsible for xenobiotic detoxification. There were also 392 down-regulated genes including many involved in metabolic homeostasis, organismal development, and reproduction. Many of these oxidative-stress-induced transcriptional changes are dependent on SKN-1 action; the induction of the heat-shock response is not. When we used RNAi to inhibit genes, we found that most had no effect on either resistance to oxidative stress or longevity; however two SKN-1-dependent genes, nlp-7 and cup-4, that were up-regulated by oxidative stress were found to be required for resistance to oxidative stress and for normal life span. nlp-7 encodes a neuropeptide-like protein, expressed in neurons, while cup-4 encodes a coelomocyte-specific, ligand-gated ion channel. RNAi of nlp-7 or cup-4 increased sensitivity to oxidative stress and reduced lifespan. Among down-regulated genes, only inhibition of ent-1, a nucleoside transporter, led to increased resistance to oxidative stress; inhibition had no effect on lifespan. In contrast, RNAi of nhx-2, a Na+/H+ exchanger, extended lifespan significantly without affecting sensitivity to oxidative stress. These findings show that oxidative stress causes a transcriptional shift from growth and maintenance towards the activation of cellular defense mechanisms; many of these transcriptional alterations are SKN-1-dependent.
PMCID: PMC2762118  PMID: 19627265
oxidative stress; C. elegans; microarray; SKN-1; aging; longevity
8.  FoxO1 in dopaminergic neurons regulates energy homeostasis and targets tyrosine hydroxylase 
Nature Communications  2016;7:12733.
Dopaminergic (DA) neurons are involved in the integration of neuronal and hormonal signals to regulate food consumption and energy balance. Forkhead transcriptional factor O1 (FoxO1) in the hypothalamus plays a crucial role in mediation of leptin and insulin function. However, the homoeostatic role of FoxO1 in DA system has not been investigated. Here we report that FoxO1 is highly expressed in DA neurons and mice lacking FoxO1 specifically in the DA neurons (FoxO1 KODAT) show markedly increased energy expenditure and interscapular brown adipose tissue (iBAT) thermogenesis accompanied by reduced fat mass and improved glucose/insulin homoeostasis. Moreover, FoxO1 KODAT mice exhibit an increased sucrose preference in concomitance with higher dopamine and norepinephrine levels. Finally, we found that FoxO1 directly targets and negatively regulates tyrosine hydroxylase (TH) expression, the rate-limiting enzyme of the catecholamine synthesis, delineating a mechanism for the KO phenotypes. Collectively, these results suggest that FoxO1 in DA neurons is an important transcriptional factor that directs the coordinated control of energy balance, thermogenesis and glucose homoeostasis.
Dopaminergic neurons are important for regulating energy homeostasis. Here, the authors show the transcription factor FoxO1 negatively regulates tyrosine hydroxylase expression in midbrain dopaminergic neurons, and plays an important role in regulation of glucose homeostasis, energy expenditure, and resistance to diet-induced obesity.
PMCID: PMC5056402  PMID: 27681312
9.  Anti-adipogenic effect of Artemisia annua in diet-induced-obesity mice model 
Journal of Veterinary Science  2015;16(4):389-396.
Obesity has increased continuously in western countries during the last several decades and recently become a problem in developing countries. Currently, anti-obesity drugs originating from natural products are being investigated for their potential to overcome adverse effects associated with chemical drugs. Artemisinic acid, which was isolated from the well-known anti-malaria herb Artemisia annua (AA) L., was recently shown to possess anti-adipogenic effects in vitro. However, the anti-adipogenic effects of AA in animal models have not yet been investigated. Therefore, we conducted daily oral administration with AA water extract in a diet-induced obesity animal model and treated 3T3-L1 cells with AA to confirm the anti-adipogenic effects in the related protein expressions. We then evaluated the physiology, adipose tissue histology and mRNA expressions of many related genes. Inhibition of adipogenesis by the AA water extract was observed in vitro. In the animal model, weight gain was significantly lower in the AA treated group, but there were no changes in food intake volume or calories. Reductions in lipid droplet size and mRNA expression associated with adipogenesis were also observed in animal epididymal fat. This study is the first to report that AA has an anti-obese effects in vivo.
PMCID: PMC4701730  PMID: 26243598
adipogenesis; animal model; Artemisia annua; diet induced obesity; obesity
10.  Large Solid Hemangioblastoma in the Cerebellopontine Angle: Complete Resection Using the Transcondylar Fossa Approach 
Hemangioblastomas (HBMs) in the cerebellopontine angle (CPA) have rarely been reported. When they are within the CPA, they may be misdiagnosed as vestibular schwannoma (VS) or cystic meningioma. Therefore, differential diagnosis is important for the safe treatment of the lesion. Large solid HBMs, similar to intracranial arteriovenous malformations (AVMs), are difficult to surgically remove from an eloquent area because of their location and hypervascularity. We report a case of an HBM in the CPA, which manifested as a hearing impairment or VS. Similar to AVM surgery, the tumor was widely opened and removed en bloc without a new neurological complication using the modified transcondylar fossa approach without resection of the jugular tubercle. Accurate diagnosis, pre-operative embolization, and a tailored approach were essential for the safe treatment of the HBM in the CPA.
PMCID: PMC4231628  PMID: 25408939
Hemangioblastoma; Cerebellopontine angle
11.  A simplified one-step nuclear transfer procedure alters the gene expression patterns and developmental potential of cloned porcine embryos 
Journal of Veterinary Science  2014;15(1):73-80.
Various somatic cell nuclear transfer (SCNT) techniques for mammalian species have been developed to adjust species-specific procedures to oocyte-associated differences among species. Species-specific SCNT protocols may result in different expression levels of developmentally important genes that may affect embryonic development and pregnancy. In the present study, porcine oocytes were treated with demecolcine that facilitated enucleation with protruding genetic material. Enucleation and donor cell injection were performed either simultaneously with a single pipette (simplified one-step SCNT; SONT) or separately with different pipettes (conventional two-step SCNT; CTNT) as the control procedure. After blastocysts from both groups were cultured in vitro, the expression levels of developmentally important genes (OCT4, NANOG, EOMES, CDX2, GLUT-1, PolyA, and HSP70) were analyzed by real-time quantitative polymerase chain reaction. Both the developmental rate according to blastocyst stage as well as the expression levels CDX2, EOMES, and HSP70 were elevated with SONT compared to CTNT. The genes with elevated expression are known to influence trophectoderm formation and heat stress-induced arrest. These results showed that our SONT technique improved the development of SCNT porcine embryos, and increased the expression of genes that are important for placental formation and stress-induced arrest.
PMCID: PMC3973768  PMID: 23820223
CDX2; EOMES; HSP70; porcine; somatic cell nuclear transfer
12.  Enhancement of Transgene Expression by HDAC Inhibitors in Mouse Embryonic Stem Cells 
Development & Reproduction  2013;17(4):379-387.
Embryonic stem (ES) cells can self-renew and differentiate to various cells depending on the culture condition. Although ES cells are a good model for cell type specification and can be useful for application in clinics in the future, studies on ES cells have many experimental restraints including low transfection efficiency and transgene expression. Here, we observed that transgene expression after transfection was enhanced by treatment with histone deacetylse (HDAC) inhibitors such as trichostatin A, sodium butyrate, and valproic acid. Transfection was performed using conventional transfection reagents with a retroviral vector encoding GFP under the control of CMV promoter as a reporter. Treatment of ES cells with HDAC inhibitors after transfection increased population of GFP positive cells up to 180% compared with untreated control. ES cells showed normal expression of stem cell markers after treatment with HDAC inhibitors. Transgene expression was further enhanced by modifying transfection procedure. GFP positive cells selected after transfection were proved to have the stem cell properties. Our improved protocol for enhanced gene delivery and expression in mouse ES cells without hampering ES cell properties will be useful for study and application of ES cells.
PMCID: PMC4382945  PMID: 25949154
Mouse embryonic stem cell; HDAC inhibitor; Transfection; Enhancement; Optimization.
13.  Chromosomal Modification in Human Embryonic Stem Cells Cultured in a Feeder-Free Condition after Single Cell Dissociation using Accutase 
Human embryonic stem (ES) cells are a potential source of cells for developmental studies and for a variety of applications in transplantation therapies and drug discovery. However, human ES cells are difficult to culture and maintain at a large scale, which is one of the most serious obstacles in human ES cell research. Culture of human ES cells on MEF cells after disassociation with accutase has previously been demonstrated by other research groups. Here, we confirmed that human ES cells (H9) can maintain stem cell properties when the cells are passaged as single cells under a feeder-free culture condition. Accutase-dissociated human ES cells showed normal karyotype, stem cell marker expression, and morphology. We prepared frozen stocks during the culture period, thawed two of the human ES cell stocks, and analyzed the cells after culture with the same method. Although the cells revealed normal expression of stem cell marker genes, they had abnormal karyotypes. Therefore, we suggest that accutase-dissociated single cells can be usefully expanded in a feeder-free condition but chromosomal modification should be considered in the culture after freeze-thawing.
PMCID: PMC4282239  PMID: 25949110
Human embryonic stem cell; Single cell dissociation; Accutase; Karyotype; Freeze-thawing
14.  The Quality of Life of Patients with Good Outcomes after Anterior Circulation Aneurysm Surgery Assessed by the World Health Organization Quality of Life Instrument-Korean Version 
Even in the patients with neurologically good outcome after intracranial aneurysm surgery, their perception of health is an important outcome issue. This study aimed to investigate the quality of life (QOL) and its predictors of patients who had a good outcome following anterior circulation aneurysm surgery as using the World Health Organization Quality of Life instrument-Korean version.
We treated 280 patients with 290 intracranial aneurysms for 2 years. This questionnaire was taken and validated by 99 patients whose Glasgow Outcome Scale score was 4 and more and Global deterioration scale 3 and less at 6 months after the operation, and 85 normal persons. Each domain and facet was compared between the two groups, and a subgroup analysis was performed on the QOL values and hospital expenses of the aneurysm patients according to the type of craniotomy, approach, bleeding of the aneurysm and brain injury.
Aneurysm patients showed a lower quality of life compared with control patients in level of independence, psychological, environmental, and spiritual domains. In the environmental domain, there were significant intergroup differences according to the type of craniotomy and the surgical approach used on the patients (p<0.05). The hospital charges were also significantly different according to the type of craniotomy (p<0.05).
Despite good neurological status, patients surgically treated for anterior circulation aneurysm have a low quality of life. The craniotomy size may affect the QOL of patients who underwent an anterior circulation aneurysm surgery and exhibited a good outcome.
PMCID: PMC3483316  PMID: 23115658
Anterior circulation aneurysm; Quality of life; Craniotomy size; Surgical approach
15.  Genetic Dissection of Late-Life Fertility in Caenorhabditis elegans 
The large post-reproductive life span reported for the free-living hermaphroditic nematode, Caenorhabditis elegans, which lives for about 10 days after its 5-day period of self-reproduction, seems at odds with evolutionary theory. Species with long post-reproductive life spans such as mammals are sometimes explained by a need for parental care or transfer of information. This does not seem a suitable explanation for C elegans. Previous reports have shown that C elegans can regain fertility when mated after the self-fertile period but did not report the functional limits. Here, we report the functional life span of the C elegans germ line when mating with males. We show that C elegans can regain fertility late in life (significantly later than in previous reports) and that the end of this period corresponds quite well to its 3-week total life span. Genetic analysis reveals that late-life fertility is controlled by conserved pathways involved with aging and dietary restriction.
PMCID: PMC3148761  PMID: 21622982
Reproduction; Aging; Evolution; Dietary restriction; Genetics
16.  Clinical and hematologic manifestations in patients with Diamond Blackfan anemia in Korea 
The Korean Journal of Hematology  2012;47(2):131-135.
Diamond Blackfan anemia (DBA), characterized by impaired red cell production, is a rare condition that is usually symptomatic in early infancy. The purpose of this study was to assess nationwide experiences of DBA encountered over a period of 20 years.
The medical records of 56 patients diagnosed with DBA were retrospectively reviewed from November 1984 to July 2010. Fifteen institutions, including 13 university hospitals, participated in this study.
The male-to-female ratio of patients with DBA was 1.67:1. The median age of diagnosis was 4 months, and 74.1% were diagnosed before 1 year of age. From 2000 to 2009, annual incidence was 6.6 cases per million. Excluding growth retardation, 38.2% showed congenital defects: thumb deformities, ptosis, coarctation of aorta, ventricular septal defect, strabismus, etc. The mean hemoglobin concentration was 5.1±1.9 g/dL, mean corpuscular volume was 93.4±11.6 fL, and mean number of reticulocytes was 19,700/mm3. The mean cellularity of bone marrow was 75%, with myeloid:erythroid ratio of 20.4:1. After remission, 48.9% of patients did not need further steroids. Five patients with DBA who received hematopoietic transplantation have survived. Cancer developed in 2 cases (3.6%).
The incidence of DBA is similar to data already published, but our study had a male predilection. Although all patients responded to initial treatment with steroids, about half needed further steroids after remission. It is necessary to collect further data, including information regarding management pathways, from nationwide DBA registries, along with data on molecular analyses.
PMCID: PMC3389062  PMID: 22783360
Diamond Blackfan anemia; Anemia; Congenital defects
17.  Isolated Sphenoid Sinus Mucocele Presenting as Third Nerve Palsy 
A sphenoid mucocele often presents late due to its deep seated anatomical site. And it has varied presentation due to its loose relationship to the cavernous sinus and the base of the skull. We describe a case of large sphenoid sinus mucocele. A middle aged old man suddenly developed third cranial nerve palsy. Brain imaging study revealed an isolated sphenoid sinus mucocele, compressing right cavernous sinus. Endoscopic marsupialization of the mucocele via transnasal approach led to complete resolution of the third cranial nerve palsy. Involvement of the third cranial nerve in isolated mucocele is rare but important neurosurgical implications which must be excluded. In addition, proper and timely treatment must be performed to avoid permanent neurologic deficit.
PMCID: PMC2982917  PMID: 21113366
Sphenoid sinus mucocele; Third nerve palsy; Transnasal approach
18.  The Ketogenic Diet Suppresses the Cathepsin E Expression Induced by Kainic Acid in the Rat Brain 
Yonsei Medical Journal  2010;51(5):653-660.
The ketogenic diet has long been used to treat epilepsy, but its mechanism is not yet clearly understood. To explore the potential mechanism, we analyzed the changes in gene expression induced by the ketogenic diet in the rat kainic acid (KA) epilepsy model.
Materials and Methods
KA-administered rats were fed the ketogenic diet or a normal diet for 4 weeks, and microarray analysis was performed with their brain tissues. The effects of the ketogenic diet on cathepsin E messenger ribonucleic acid (mRNA) expression were analyzed in KA-administered and normal saline-administered groups with semi-quantitative and real-time reverse transcription polymerase chain reaction (RT-PCR). Brain tissues were dissected into 8 regions to compare differential effects of the ketogenic diet on cathepsin E mRNA expression. Immunohistochemistry with an anti-cathepsin E antibody was performed on slides of hippocampus obtained from whole brain paraffin blocks.
The microarray data and subsequent RT-PCR experiments showed that KA increased the mRNA expression of cathepsin E, known to be related to neuronal cell death, in most brain areas except the brain stem, and these increases of cathepsin E mRNA expression were suppressed by the ketogenic diet. The expression of cathepsin E mRNA in the control group, however, was not significantly affected by the ketogenic diet. The change in cathepsin E mRNA expression was greatest in the hippocampus. The protein level of cathepsin E in the hippocampus of KA-administered rat was elevated in immunohistochemistry and the ketogenic diet suppressed this increase.
Our results showed that KA administration increased cathepsin E expression in the rat brain and its increase was suppressed by the ketogenic diet.
PMCID: PMC2908849  PMID: 20635438
Cathepsin E; epilepsy; kainic acid; ketogenic diet; neuroprotection
19.  Gene Expression Profiling of Aging in Multiple Mouse Strains: Identification of Aging Biomarkers and Impact of Dietary Antioxidants 
Aging cell  2009;8(4):484-495.
We used DNA microarrays to identify panels of transcriptional markers of aging that are differentially expressed in young (5-month) and old (25-month) mice of multiple inbred strains (129sv, BALB/c, CBA, DBA, B6, C3H, and B6C3F1). In the heart, age-related changes of five genes were studied throughout the mouse lifespan: complement component 4, chemokine ligand 14, component of Sp100-rs, phenylalanine hydroxylase, and src family associated phosphoprotein 2. A similar analysis in the brain (cerebellum) involved complement component 1q (alpha polypeptide), complement component 4, P lysozyme structural, glial fibrillary acidic protein, and cathepsin S. Caloric restriction inhibited age-related expression of these genes in both tissues. Parametric analysis of gene set enrichment (PAGE) identified several biological processes that are induced with aging in multiple mouse strains. We also tested the ability of dietary antioxidants to oppose these transcriptional markers of aging. Lycopene, resveratrol, acetyl-L-carnitine, and Tempol were as effective as caloric restriction in the heart, and α-lipoic acid and coenzyme Q10 were as effective as caloric restriction in the cerebellum. These findings suggest that transcriptional biomarkers of aging in mice can be used to estimate the efficacy of aging interventions on a tissue-specific basis.
PMCID: PMC2733852  PMID: 19555370
aging; mouse; biomarkers; microarray; antioxidants; caloric restriction
20.  DNA damage-induced alterations in chromatin contribute to genomic integrity and age-related changes in gene expression 
Cell  2008;135(5):907-918.
Genomic instability and alterations in gene expression are hallmarks of eukaryotic aging. The yeast histone deacetylase Sir2 silences transcription and stabilizes repetitive DNA, but during aging or in response to a DNA break, the Sir complex relocalizes to sites of genomic instability, resulting in the desilencing of genes that cause sterility, a characteristic of yeast aging. Using embryonic stem cells, we show that mammalian Sir2, SIRT1, represses repetitive DNA and a functionally diverse set of genes across the mouse genome. In response to DNA damage, SIRT1 dissociates from these loci and relocalizes to DNA breaks to promote repair, resulting in transcriptional changes that parallel those in the aging mouse brain. Increased SIRT1 expression promotes survival in a mouse model of genomic instability and suppresses age-dependent transcriptional changes. Thus, DNA damage-induced redistribution of SIRT1 and other chromatin modifying proteins may be a conserved mechanism of aging in eukaryotes.
PMCID: PMC2853975  PMID: 19041753
epigenetics; sirtuin; chromatin; histone; DNA repair
21.  Efficacy and safety of deferiprone (Ferriprox), an oral iron-chelating agent, in pediatric patients 
Iron overload is a predictable and life-threatening complication in patients dependent on the regular transfusion of RBCs. The aims of this study were to investigate the efficacy and safety of deferiprone in a variety of pediatric hematologic and/or oncologic patients with a high iron overload.
Seventeen patients (age: 1.1-20.4 years; median: 10.6 years) from 7 hospitals who were treated with deferiprone from 2006 to 2009 were enrolled in this study. Medical records of enrolled patients were reviewed retrospectively.
Serum ferritin levels were 4,677.8±1,130.9 µg/L at baseline compared to 3,363.9±1,149.7 µg/L at the end of deferiprone treatment (P=0.033). Only 1 patient developed neutropenia as a complication.
Deferiprone treatment is relatively safe for pediatric patients suffering from various hematologic and oncologic diseases that require RBC transfusions as part of treatment. However, the potential development of critical complications such as agranulocytosis and/or neutropenia remains a concern.
PMCID: PMC2983007  PMID: 21120164
Deferiprone; Iron overload; Transfusion; Neutropenia
22.  Differential effect of α- and γ-tocopherol supplementation in age-related transcriptional alterations in heart and brain of B6/C3H F1 mice 
The Journal of nutrition  2008;138(6):1010-1018.
To investigate the global effects of vitamin E supplementation on aging, we used high-density oligonucleotide arrays to measure transcriptional alterations in the heart and brain (neocortex) of 30-month-old B6C3F1 mice supplemented with α- and γ-tocopherol since middle age (15 months). Gene expression profiles were obtained from 5- and 30-month-old controls and 30-month-old mice supplemented with α-tocopherol (1g/kg), or a mixture of α- and γ-tocopherol (500mg/kg of each tocopherol). In the heart, both tocopherol supplemented diets were effective in inhibiting the expression of genes previously associated with cardiomyocyte hypertrophy and increased innate immunity, while having a moderate effect on age-related transcriptional alterations linked to the stress response and protein synthesis. In the brain, induction of genes encoding ribosomal proteins and proteins involved in ATP biosynthesis was observed with aging and was markedly prevented by the mixture of α- and γ-tocopherol supplementation, but not by α-tocopherol alone. These results demonstrate that middle age-onset dietary supplementation with α- and γ-tocopherol can partially prevent age-associated transcriptional changes and that these effects are tissue- and tocopherol-specific.
PMCID: PMC2768425  PMID: 18492827
vitamin E; aging; microarray; heart; brain
23.  Microsurgical Experience with Supraorbital Keyhole Operations on Anterior Circulation Aneurysms 
Conventional pterional approach is a commonly used neurosurgical technique for the treatment of cerebral aneurysms. However, this technique requires more extensive brain exposure than other key hole approaches and is sometimes associated with surgical traumatization or cosmetic problems. The aim of this study was to compare the postoperative outcome between pterional and supraorbital keyhole approaches in the patients with anterior circulation aneurysms.
The authors reviewed patients with anterior circulation aneurysms who underwent aneurysm clipping via pterional or supraorbital keyhole approach at a single institute over a period of 2 years. Ninety-eight patients harboring 108 aneurysms were included in this study. Various outcomes were recorded, which included clinical grade, cosmetic problems, patients' satisfaction and complications such as chewing discomfort, frontal muscle weakness, hyposmia, infection.
The supraorbital approach exhibited a shorter operation time compared with the pterional approach. Complications such as chewing discomfort occurred less frequently in the supraorbital approach group. Moreover, the cosmetic outcome was significantly better in the supraorbital group than in the pterional group.
The supraorbital keyhole approach reduced intra- and postoperative complications, including chewing discomfort and cosmetic disturbances, compared with the conventional pterional approach.
PMCID: PMC2744018  PMID: 19763211
Pterional approach; Supraorbital approach; Aneurysm; Clipping; Cosmetic outcome
24.  Acute Physiology and Chronic Health Evaluation II and Simplified Acute Physiology Score II in Predicting Hospital Mortality of Neurosurgical Intensive Care Unit Patients 
Journal of Korean Medical Science  2009;24(3):420-426.
We study the predictive power of Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) in neurosurgical intensive care unit (ICU) patients. Retrospective investigation was conducted on 672 consecutive ICU patients during the last 2 yr. Data were collected during the first 24 hours of admission and analyzed to calculate predicted mortality. Mortality predicted by two systems was compared and, multivariate analyses were then performed for subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI) patients. Observed mortality was 24.8% whereas predicted mortalities were 37.7% and 38.4%, according to APACHE II and SAPS II. Calibration curve was close to the line of perfect prediction. SAPS II was not statistically significant according to a Lemeshow-Hosmer test, but slightly favored by area under the curve (AUC). In SAH patients, SAPS II was an independent predictor for mortality. In TBI patients, both systems had independent prognostic implications. Scoring systems are useful in predicting mortality and measuring performance in neurosurgical ICU setting. TBI patients are more affected by systemic insults than SAH patients, and this discrepancy of predicting mortality in each neurosurgical disease prompts us to develop a more specific scoring system targeted to cerebral dysfunction.
PMCID: PMC2698186  PMID: 19543503
APACHE; Intensive Care Units; Mortality; Simplified Acute Physiologic Score; Subarachnoid Hemorrhage; Brain Injuries
25.  The Clinical Outcomes of 75 Consecutive Patients with Cervical Carotid Artery Stenosis Treated by Carotid Artery Stenting 
The purpose of this study was to analyze the clinical outcome of 75 consecutive patients with cervical carotid artery stenosis and who were treated by carotid artery stenting (CAS) only.
From February 2003 to June 2008, there were 78 stents placed in 75 symptomatic patients (mean age : 67.3 years); 69 patients had carotid stenosis ≥70%, and 6 patients had asymptomatic stenosis ≥80%. No carotid endarterectomy (CEA) was performed during the same period. The patients were clinically followed-up for a mean of 20.1 months.
The procedures were technically successful in all cases. Three (3.8%) patients had procedure-related complications. During the 30-day postprocedural period, there were no restenosis or major stroke. Minor stroke was noticed in 3 (3.8%) patients and 1 (1.3%) of the 75 patients suddenly expired 2 days after discharge. There were no new neurological symptoms that developed during the clinical follow-up period. The results of our series were not inferior to those the previously published in CAS studies, and in fact they were better.
Our results suggest that CAS may be safe and useful for the treatment of cervical carotid artery stenosis when it is used as the first line treatment in those institutions that lack enough experience with CEA.
PMCID: PMC2711232  PMID: 19609418
Carotid artery stenosis; Carotid artery stenting; Carotid endarterectomy; Stroke

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