Cognitive and brain reserve in conversion and reversion in patients with mild cognitive impairment over 12 months of follow-up

Introduction: Two reserve hypotheses have been proposed to account for the observed disjunction between the degree of brain pathology and its clinical manifestations. This study investigated whether cognitive reserve (CR), taken here as educational attainment and premorbid IQ, or brain reserve (BR; i.e., brain volume) is associated with progression and regression in patients with mild cognitive impairment (MCI) over a 12-month follow-up. Method: Patients with MCI (n = 123) were prospectively enrolled. The Mini-Mental State Examination, the Japanese version of the Cognitive subscale of the Alzheimer’s Disease Assessment Scale, the Clinical Dementia Rating (CDR), the Frontal Assessment Battery, the Neuropsychiatric Inventory, magnetic resonance imaging (MRI), and quantitative single-photon emission computed tomography were performed at intake and again at 12-month follow-up. Patients were classified into three groups: no change, conversion, and reversion. Conversion was defined as a change in CDR from 0.5 to 1, and reversion as a change from 0.5 to 0. Results: Voxel-based morphometry MRI revealed no significant differences in entorhinal and hippocampal gray matter loss among the groups. Patients with reversion had higher premorbid IQ (p = .03, η_p² = .35) as measured by the Japanese version of the National Adult Reading Test, higher atrophy ratio (hippocampal volume/whole brain volume; p = .04, η_p² = .89) at baseline, and better cognitive performance (p < .001) during the 12-month follow-up than those with conversion did. There were no statistically significant differences among the three groups in terms of years of education. Conclusion: Multinomial logistic regression analysis revealed that higher CR contributed to protecting against cognitive decline during the 12-month follow-up, whereas higher BR at baseline was the strongest predictor for reversion and conversion.     

Intracranial EEG potentials estimated from MEG sources: A new approach to correlate MEG and iEEG data in epilepsy

Detection of epileptic spikes in MagnetoEncephaloGraphy (MEG) requires synchronized neuronal activity over a minimum of 4cm2. We previously validated the Maximum Entropy on the Mean (MEM) as a source localization able to recover the spatial extent of the epileptic spike generators. The purpose of this study was to evaluate quantitatively, using intracranial EEG (iEEG), the spatial extent recovered from MEG sources by estimating iEEG potentials generated by these MEG sources. We evaluated five patients with focal epilepsy who had a pre‐operative MEG acquisition and iEEG with MRI‐compatible electrodes. Individual MEG epileptic spikes were localized along the cortical surface segmented from a pre‐operative MRI, which was co‐registered with the MRI obtained with iEEG electrodes in place for identification of iEEG contacts. An iEEG forward model estimated the influence of every dipolar source of the cortical surface on each iEEG contact. This iEEG forward model was applied to MEG sources to estimate iEEG potentials that would have been generated by these sources. MEG‐estimated iEEG potentials were compared with measured iEEG potentials using four source localization methods: two variants of MEM and two standard methods equivalent to minimum norm and LORETA estimates. Our results demonstrated an excellent MEG/iEEG correspondence in the presumed focus for four out of five patients. In one patient, the deep generator identified in iEEG could not be localized in MEG. MEG‐estimated iEEG potentials is a promising method to evaluate which MEG sources could be retrieved and validated with iEEG data, providing accurate results especially when applied to MEM localizations. Hum Brain Mapp 37:1661–1683, 2016. © 2016 Wiley Periodicals, Inc .     

Contrast agent comparison for three‐dimensional micro‐CT angiography: A cadaveric study

Barium sulfate and lead oxide contrast media are frequently used for cadaver‐based angiography studies. These contrast media have not previously been compared to determine which is optimal for the visualisation and measurement of blood vessels. In this study, the lower limb vessels of 16 embalmed Wistar rats, and four sets of cannulae of known diameter, were injected with one of three different contrast agents (barium sulfate and resin, barium sulfate and gelatin, and lead oxide combined with milk powder). All were then scanned using micro‐computed tomography (CT) angiography and 3‐D reconstructions generated. The number of branching generations of the rat lower limb vessels were counted and compared between the contrast agents using ANOVA. The diameter of the contrast‐filled cannulae, were measured and used to calculate the accuracy of the measurements by comparing the bias and variance of the estimates. Intra‐ and inter‐observer reliability were calculated using intra‐class correlation coefficients. There was no significant difference (mean difference [MD] 0.05; MD 95% confidence interval [CI] ‐0.83 to 0.93) between the number of branching generations for barium sulfate‐resin and lead oxide‐milk powder. Barium sulfate‐resin demonstrated less bias and less variance of the estimates (MD 0.03; standard deviation [SD] 1.96 mm) compared to lead oxide‐milk powder (MD 0.11; SD 1.96 mm) for measurements of contrast‐filled cannulae scanned at high resolution. Barium sulfate‐resin proved to be more accurate than lead oxide‐milk powder for high resolution micro‐CT scans and is preferred due to its non‐toxicity. This technique could be applied to any embalmed specimen model. Copyright © 2016 John Wiley & Sons, Ltd.     

Physiological regulation in cigarette exposed infants: an examination of potential moderators

The primary purpose of this study was to examine pathways from prenatal cigarette exposure to physiological regulation at 2 months of age. Specifically, we explored the possibility that any association between prenatal cigarette exposure and infant physiological regulation was moderated by fetal growth, prenatal or postnatal environmental tobacco smoke (ETS) exposure or maternal depressive symptomatology during pregnancy. We evaluated whether exposed infants who were also exposed to ETS after birth, were small for gestational age (SGA) or had mothers with higher depressive symptoms during pregnancy had the highest levels of physiological dysregulation. Respiratory sinus arrhythmia (RSA) was obtained from 234 (166 exposed and 68 nonexposed) infants during sleep. As expected, cigarette-exposed infants had significantly lower RSA than nonexposed infants. This association was not moderated by prenatal or postnatal ETS exposure, or maternal depressive symptomatology during pregnancy. However, small for gestational age status did moderate this association such that nonexposed infants who were not small for gestational age had a significantly higher RSA than nonexposed small for gestational age infants and exposed infants. These findings provide additional evidence that prenatal cigarette exposure is directly associated with dysregulation during infancy.     

Inhibitory effects of an ellagic acid glucoside, okicamelliaside, on antigen-mediated degranulation in rat basophilic leukemia RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice

Degranulation inhibitors in plants are widely used for prevention and treatment of immediate-type allergy. We previously isolated a new ellagic acid glucoside, okicamelliaside (OCS), from Camellia japonica leaves for use as a potent degranulation inhibitor. Crude extracts from leaves also suppressed allergic conjunctivitis in rats. In this study, we evaluated the in vivo effect of OCS using a pure sample and performed in vitro experiments to elucidate the mechanism underlying the extraordinary high potency of OCS and its aglycon. The IC(50) values for degranulation of rat basophilic leukemia cells (RBL-2H3) were 14 nM for OCS and 3 μM for aglycon, indicating that the two compounds were approximately 2 to 3 orders of magnitude more potent than the anti-allergic drugs ketotifen fumarate, DSCG, and tranilast (0.17, 3, and >0.3 mM, respectively). Antigen-induced calcium ion (Ca(2+)) elevation was significantly inhibited by OCS and aglycon at all concentrations tested (p<0.05). Upstream of the Ca(2+) elevation in the principle signaling pathway, phosphorylation of Syk (Tyr525/526) and PLCγ-1 (Tyr783 and Ser1248) were inhibited by OCS and aglycon. In DNA microarray-screening test, OCS inhibited expression of proinflammatory cytokines [interleukin (IL)-4 and IL-13], cytokine-producing signaling factors, and prostaglandin-endoperoxidase 2, indicating that OCS broadly inhibits allergic inflammation. During passive cutaneous anaphylaxis in mice, OCS significantly inhibited vascular hyperpermeability by two administration routes: a single intraperitoneal injection at 10 mg/kg and per os at 5 mg/kg for 7 days (p<0.05). These results suggest the potential for OCS to alleviate symptoms of immediate-type allergy.     

Telomere/Telomerase system: a new target of statins pleiotropic effect?

Statins are well established drugs for primary and secondary prevention of coronary artery disease (CAD). Despite the well-known ability of statins to lower cholesterol, it is now clear that clinical benefits are also substantially higher than expected and several clinical trials, like JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin trial) have indicated that such clinical effects are independent of cholesterol reduction. These cholesterol-independent actions have been named "pleiotropic effects" and include: anti-oxidation and anti-inflammatory effects, modulation of immune activation, stabilization of atherosclerotic plaque, decreased platelet activation, inhibition of cardiac hypertrophy, reduction of cytokine-mediated vascular smooth muscle cell (VSMC) proliferation and improvement of endothelial function. Recently, additional pleiotropic effects of statins on "cellular senescence" have been seen in different cell types, including endothelial progenitor cells (EPC), endothelial cells (EC), VSMC and chondrocytes. At the molecular level, the effect of statins on cellular senescence could be mediated by their interaction with the telomere/telomerase system. Recent evidence suggests that the anti-aging effects of statins are linked to their ability to inhibit telomere shortening by reducing either directly and indirectly oxidative telomeric DNA damage, as well as by a telomere capping proteins dependent mechanism. In this review, we discuss the pleiotropic effects of statins, focusing on the telomere/telomerase system. We will also present our current findings regarding leukocyte telomere length in very old people with myocardial infarction on statin therapy.     

蒙成药壮西六味散的鉴别

目的:建立蒙成药壮西六味散的鉴别方法,提高该药的质量标准。方法:化学法和薄层色谱法。结果:建立了该药所含的寒水石、荜茇、红花、木香和白豆蔻5味药材的鉴别方法。结论:本实验方法操作简便,重复性好,专属性强,结果稳定可靠,可用于该药的定性质控。     

Haplotype of thrombomodulin gene associated with plasma thrombomodulin level and deep vein thrombosis in the Japanese population

INTRODUCTION: Thrombomodulin (TM) is an essential cofactor in protein C activation by thrombin. Here, we evaluated the contribution of genetic variations in the TM gene to soluble TM (sTM) level and deep vein thrombosis (DVT) in Japanese. PATIENTS AND METHODS: We sequenced the TM putative promoter, exon, and 3'-untranslated region in DVT patients (n=118). Among 17 genetic variations we identified, two missense mutations (R385K, D468Y) and three common single nucleotide polymorphisms (-202G>A, 2487A>T, 2729A>C) were genotyped in a general population of 2247 subjects (1032 men and 1215 women) whose sTM levels were measured. We then compared the frequency of these mutations in DVT patients with that in the age, body mass index-adjusted population-based controls. RESULTS: We identified one neutral mutation (H381) and three missense mutations (R385K; n=2, A455V; n=53 heterozygous, n=14 homozygous, D468Y; n=2) of TM in the DVT patients. Age-adjusted mean values of sTM were lower in C-allele carriers of 2729A>C than in noncarriers in the Japanese general population (women: 16.7+/-0.3 U/ml vs. 17.9+/-0.2 U/ml, p<0.01, men: 19.4+/-0.3 U/ml vs. 20.4+/-0.3 U/ml, p=0.03). Additionally, the CC genotype of this mutation was more common in the male DVT patients than in the male individuals of the general population (odds ratio=2.76, 95% confidence interval=1.14-6.67; p=0.02). This mutation was in linkage disequilibrium (r-square>0.9) with A455V mutation. CONCLUSIONS: TM mutations, especially those with a haplotype consisting of 2729A>C and A455V missense mutation, affect sTM levels, and may be associated with DVT in Japanese.