NOX Inhibitors - A Promising Avenue for Ischemic Stroke.

NADPH-oxidase (NOX) mediated superoxide originally found on leukocytes, but now recognized in several types of cells in the brain. It has been shown to play an important role in the progression of stroke and related cerebrovascular disease. NOX is a multisubunit complex consisting of 2 membrane-associated and 4 cytosolic subunits. NOX activation occurs when cytosolic subunits translocate to the membrane, leading to transport electrons to oxygen, thus producing superoxide. Superoxide produced by NOX is thought to function in long-term potentiation and intercellular signaling, but excessive production is damaging and has been implicated to play an important role in the progression of ischemic brain. Thus, inhibition of NOX activity may prove to be a promising treatment for ischemic brain as well as an adjunctive agent to prevent its secondary complications. There is mounting evidence that NOX inhibition in the ischemic brain is neuroprotective, and targeting NOX in circulating immune cells will also improve outcome. This review will focus on therapeutic effects of NOX assembly inhibitors in brain ischemia and stroke. However, the lack of specificity and toxicities of existing inhibitors are clear hurdles that will need to be overcome before this class of compounds could be translated clinically

Students' ideas about different representations of the past : South Korean adolescents interpret historical film

This thesis explores the ways in which secondary school students interpret different\ud representations of the past as portrayed in the film. It focuses on the question of how they set\ud the film director's view within a sociocultural context, and how they conceptualise what\ud constitutes acceptable historical knowledge. Ninety-six secondary school students in South\ud Korea viewed two sets of historical films that vary in terms of authorship, period, and genre.\ud The viewings were followed by semi-structured interviews, which aimed to investigate a\ud range of students' approaches to different representations produced at a given place and time.\ud This thesis argues that acknowledging the structuring of historical knowledge as a part of\ud cultural practice enabled students to make a shift in their picture of the past: from the idea of\ud the past as being reproduced to that of the past as being organised and reconstructed. A range\ud of ideas about historical knowledge, from a direct report of the event through an\ud idiosyncratic interpretation of a literary past to systematic mediation of historical reality, was\ud identified.\ud Through analysis of students' approaches to revision of the past, this thesis also discusses the\ud relationship between ideas about the role of perspective in history and ideas about the\ud reconfiguration of the past for the present. Students tended to assume that more committed\ud perspectives were likely to subject historical representations to greater revision of history.\ud Students' ideas about changing representations of the past reflected their presuppositions\ud about change of viewpoints in historical enquiry, mainly either in an empirical or cultural\ud sense rather than in a methodological sense.\ud Given students' tendency to conceive historical representations as being subject to\ud perspective mainly fuelled by present interests, it is crucial to provide an opportunity for\ud them to frame an historical account as an answer to a particular question, attributing a\ud positive role to perspectival views of the past

The Effect Of The Relationships Between Affiliated Firms On Direction Of Income Shifting Within Business Groups

In this study, we examined how income shifting performs among affiliates in a business group to maximize the benefits of the entire business group in terms of minimizing the tax burden, with a particular focus on the direction of income shifting between affiliates within the business group. We find that tax-related decision-making for the entire business group is affected by the relationships between the affiliated firms, that is, the ownership structure of the whole business group. To analyze the ownership structure, we use centrality measures in a social network analysis. The results show that affiliates with the higher outdegree-centrality; that is, firms investing more shareholdings in other affiliates have a tendency to perform more income shifting. On the other hand, the affiliates with high indegree-centrality, that is, firms which are owned by other affiliates, were revealed to be given the income shifting from other affiliated firms to minimize the tax burden of the entire business group

Glutathione Suppresses Cerebral Infarct Volume and Cell Death after Ischemic Injury: Involvement of FOXO3 Inactivation and Bcl2 Expression

Ischemic stroke interrupts the flow of blood to the brain and subsequently results in cerebral infarction and neuronal cell death, leading to severe pathophysiology. Glutathione (GSH) is an antioxidant with cellular protective functions, including reactive oxygen species (ROS) scavenging in the brain. In addition, GSH is involved in various cellular survival pathways in response to oxidative stress. In the present study, we examined whether GSH reduces cerebral infarct size after middle cerebral artery occlusion in vivo and the signaling mechanisms involved in the promotion of cell survival after GSH treatment under ischemia/reperfusion conditions in vitro. To determine whether GSH reduces the extent of cerebral infarction, cell death after ischemia, and reperfusion injury, we measured infarct size in ischemic brain tissue and the expression of claudin-5 associated with brain infarct formation. We also examined activation of the PI3K/Akt pathway, inactivation of FOXO3, and expression of Bcl2 to assess the role of GSH in promoting cell survival in response to ischemic injury. Based on our results, we suggest that GSH might improve the pathogenesis of ischemic stroke by attenuating cerebral infarction and cell death

Temperature measurements of heated microcantilevers using scanning thermoreflectance microscopy

We report the development of scanning thermoreflectance thermometry and its application for steady and dynamic temperature measurement of a heated microcantilever. The local thermoreflectance signal of the heated microcantilever was calibrated to temperature while the cantilever was under steady and periodic heating operation. The temperature resolution of our approach is 0.6 K, and the spatial resolution is 2 μm, which are comparable to micro-Raman thermometry. However, the temporal resolution of our approach is about 10 μsec, which is significantly faster than micro-Raman thermometry. When the heated microcantilever is periodically heated with frequency up to 100 kHz, we can measure both the in-phase and out-of-phase components of the temperature oscillation. For increasing heating frequency, the measured cantilever AC temperature distribution tends to be confined in the vicinity of the heater region and becomes increasingly out of phase with the driving signal. These results compare well with finite element simulations

PRC2-Mediated H3K27me3 Contributes to Transcriptional Regulation of FIT-Dependent Iron Deficiency Response

Iron is an essential micronutrient for nearly all organisms, but excessive iron can lead to the formation of cytotoxic reactive oxygen species. Therefore, iron acquisition and homeostasis must be tightly regulated. Plants have evolved complex mechanisms to optimize their use of iron, which is one of the most limiting nutrients in the soil. In particular, transcriptional regulation is vital for regulating iron in plants, and much work has revealed the role of transcription factors on this front. Our study adds novel insights to the transcriptional regulation of iron homeostasis in plants by showing that chromatin remodeling via histone 3 lysine 27 trimethylation (H3K27me3) modulates the expression of FIT-dependent genes under iron deficiency. We provide evidence that FIT-dependent iron acquisition genes, IRT1 and FRO2, as well as FIT itself are direct targets of PRC2-mediated H3K27me3. In the clf mutant, which lacks the predominant H3K27 tri-methyltransferase, induction of FIT, FRO2, IRT1, and other FIT-regulated genes in roots is significantly higher under iron deficient conditions than in wild type. Furthermore, we observe that clf mutants are more tolerant to iron deficiency than wild type, indicating that gene expression levels appear to be limiting the plants ability to access iron. We propose that H3K27me3 attenuates the induction of FIT-target genes under iron deficiency and hypothesize that this may serve as a mechanism to restrict the maximum level of induction of iron acquisition genes to prevent iron overload

House dust mite-specific immunoglobulin E and longitudinal exhaled nitric oxide measurements in children with atopic asthma

PurposeHouse dust mite (HDM) has been suggested to be the most important aeroallergen responsible for atopic asthma in Korea. We aimed to investigate that specific IgE antibodies to HDM and other common indoor aeroallergens contribute differently to total serum IgE and show different relationships with longitudinal fractional exhaled nitric oxide (FeNO) measurements in Korean atopic asthmatic patients.MethodsA total of 193 children aged 8 to 16 years with intermittent or mild persistent atopic asthma were recruited. Sera were assayed for total IgE and specific IgE antibodies to HDM and other common indoor allergens. FeNO was serially measured 10 times or more over 2 years when subjects were not receiving controller medications.ResultsIn 152 children who completed the study, IgE antibodies to specific HDM were more prevalent than those to other common indoor aeroallergens. In addition, IgE antibody titers to HDM were the strongest contributor to total IgE increases. Furthermore, only HDM-specific IgE antibody titer significantly correlated with maximum FeNO (r=0.21, P=0.029) and the rate of FeNO higher than 21 parts per billion (ppb) (r=0.30, P=0.002). Eight patients (5%) were found to have maximum FeNO of 21 ppb or less, suggesting the presence of a low FeNO phenotype among atopic asthmatic patients.ConclusionThe quantity of HDM-specific IgE antibody provides a possible explanation for increases of total IgE and significantly correlates with the amount and frequency of FeNO increases in Korean atopic asthmatic patients

Triage results of children who visited the emergency department via emergency medical service providers: an observational study in a regional emergency medical center

Purpose We aimed to investigate the triage results and the degree of agreement between prehospital and hospital stages of pediatric patients who visited the emergency department (ED) via emergency medical service providers (EMSP) in comparison with adult patients. Methods We retrospectively reviewed 8,152 pediatric patients who visited a regional emergency medical center ED via EMSP from January 2015 to December 2015. Pediatric patients were defined as younger than 15 years according to the Korean Triage and Acuity Scale (KTAS). Given the difference of the triage tools of the prehospital (EMSP) and hospital (KTAS) stages, we performed the re-triage into “critical” and “non-critical”. Comparisons of characteristics between pediatric and adult patients were made using chi-square tests. The degree of agreement between the tools was analyzed using κanalysis. Results Of 8,152 patients, 654 (8.0%) were pediatric patients. Direct medical control was more frequently performed to adult patients (P < 0.001). Critical patients were more common among adults (12.2% by KTAS, 24.8% by EMSP) than children (3.5% by KTAS, 14.1% by EMSP). The κ value of pediatric patients was lower than that of adult patients (0.09 [poor]; 95% confidence interval [CI], 0.01-0.18 vs. 0.38 [fair]; 95% CI, 0.35-0.40). Conclusion Pediatric patients transferred by EMSP showed lower severity and degree of agreements of the triage results between prehospital and hospital stages than adult patients. It is necessary to pay particular attention to pediatric triage in a pre-hospital setting

Computed tomographic evaluation of abdominal fat in minipigs

Computed tomography (CT) exams were conducted to determine the distribution of abdominal fat identified based on the CT number measured in Hounsfield Units (HU) and to measure the volume of the abdominal visceral and subcutaneous fat in minipigs. The relationship between the CT-based fat volumes of several vertebral levels and the entire abdomen and anthropometric data including the sagittal abdominal diameter and waist circumference were evaluated. Moreover, the total fat volumes at the T11, T13, L3, and L5 levels were compared with the total fat volume of the entire abdomen to define the landmark of abdominal fat distribution. Using a single-detector CT, six 6-month-old male minipigs were scanned under general anesthesia. Three radiologists then assessed the HU value of visceral and subcutaneous abdominal fat by drawing the region of interest manually at the T11, T13, L1, L3, and L5 levels. The CT number and abdominal fat determined in this way by the three radiologists was found to be correlated (intra-class coefficient = 0.9). The overall HU ranges for the visceral and subcutaneous fat depots were -147.47 to -83.46 and -131.62 to -90.97, respectively. The total fat volume of the entire abdomen was highly correlated with the volume of abdominal fat at the T13 level (r = 0.97, p < 0.0001). These findings demonstrate that the volume of abdominal adipose tissue measured at the T13 level using CT is a strong and reliable predictor of total abdominal adipose volume

Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation

Background/AimsThe dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT).MethodsTwo sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT.ResultsIn the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively.ConclusionsA reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT