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.
oxidative stress; C. elegans; microarray; SKN-1; aging; longevity
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.
Anterior circulation aneurysm; Quality of life; Craniotomy size; Surgical approach
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.
Reproduction; Aging; Evolution; Dietary restriction; Genetics
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.
Sphenoid sinus mucocele; Third nerve palsy; Transnasal approach
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.
Cathepsin E; epilepsy; kainic acid; ketogenic diet; neuroprotection
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.
aging; mouse; biomarkers; microarray; antioxidants; caloric restriction
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.
epigenetics; sirtuin; chromatin; histone; DNA repair
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.
Deferiprone; Iron overload; Transfusion; Neutropenia
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.
vitamin E; aging; microarray; heart; brain
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.
Pterional approach; Supraorbital approach; Aneurysm; Clipping; Cosmetic outcome
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.
APACHE; Intensive Care Units; Mortality; Simplified Acute Physiologic Score; Subarachnoid Hemorrhage; Brain Injuries
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.
Carotid artery stenosis; Carotid artery stenting; Carotid endarterectomy; Stroke
The title compound, C17H19N4
+·Br−, is built up from 1,3-bis[(6-methyl-2-pyridinyl)methyl]imidazolium cations and bromide anions. Each of two 6-methyl-2-pyridyl rings is rotated out of the imidazole plane, making dihedral angles of 79.90 (9) and 86.40 (9)°. The packing is consolidated by aromatic π–π interactions between the pyridine rings of neighbouring molecules [centroid–centroid distance = 3.554 (2) Å] and by weak C—H⋯N and C—H⋯Br hydrogen bonds.
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.
Diamond Blackfan anemia; Anemia; Congenital defects