Some Preformulation Studies of Pyruvic Acid and Other α-Keto Carboxylic Acids in Aqueous Solution: Pharmaceutical Formulation Implications for These Peroxide Scavengers

The purpose of this study is to assess some of the variables determining the aldol-like condensation of pyruvic acid (1), a peroxide scavenger, in aqueous solution to parapyruvic acid and higher oligomers. Its stability is compared to 3 other α-keto carboxylic acids, 2 with sterically hindered methylene groups alpha to the keto functionality (2-3) and phenylglyoxylic acid (4) with no methylene group. High-performance liquid chromatography, nuclear magnetic resonance, and liquid chromatography mass spectroscopy techniques are used in the kinetics and product analyses. 1 condensation is concentration dependent and base catalyzed above pH 7, consistent with the reaction mechanism proceeding through the attack of the fraction of the methylene group, alpha to the keto group, in its anionic form, at the keto group of a second molecule of 1. The major product is confirmed to be parapyruvic acid, but higher-order oligomers are also observed. All 3 of the other α-keto carboxylic acids 2-4 are considerably less reactive, with 4 being completely stable. Stable solutions of 1 can be prepared by the use of relatively dilute solutions maintained at slightly acidic pH values. 1 prevents the oxidation of methionine on addition of hydrogen peroxide.     

Low and High Field Magnetic Resonance for in Vivo Analysis of Seeds

Low field NMR has been successfully used for the evaluation of seed composition and quality, but largely only in crop species. We show here that 1.5T NMR provides a reliable means for analysing the seed lipid fraction present in a wide range of species, where both the seed size and lipid concentration differed by >10 fold. Little use of high field NMR has been made in seed research to date, even though it potentially offers many opportunities for studying seed development, metabolism and storage. Here we demonstrate how 17.5T and 20T NMR can be applied to image seed structure, and analyse lipid and metabolite distribution. We suggest that further technical developments in NMR/MRI will facilitate significant advances in our understanding of seed biology.     

Surgical myectomy versus alcohol septal ablation for obstructive hypertrophic cardiomyopathy: A propensity score–matched cohort

Objectives

In patients with hypertrophic cardiomyopathy, obstruction of the left ventricular outflow tract can be relieved by surgical septal myectomy or alcohol septal ablation, but uncertainty remains regarding long-term results and comparative effectiveness of alcohol septal ablation. This study aims to compare short- and long-term outcomes of the 2 procedures.

Decreased centrality of cortical volume covariance networks in autism spectrum disorders

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions characterized by atypical structural and functional brain connectivity. Complex network analysis has been mainly used to describe altered network-level organization for functional systems and white matter tracts in ASD. However, atypical functional and structural connectivity are likely to be also linked to abnormal development of the correlated structure of cortical gray matter. Such covariations of gray matter are particularly well suited to the investigation of the complex cortical pathology of ASD, which is not confined to isolated brain regions but instead acts at the systems level. In this study, we examined network centrality properties of gray matter networks in adults with ASD (n = 84) and neurotypical controls (n = 84) using graph theoretical analysis. We derived a structural covariance network for each group using interregional correlation matrices of cortical volumes extracted from a surface-based parcellation scheme containing 68 cortical regions. Differences between groups in closeness network centrality measures were evaluated using permutation testing. We identified several brain regions in the medial frontal, parietal and temporo-occipital cortices with reductions in closeness centrality in ASD compared to controls. We also found an association between an increased number of autistic traits and reduced centrality of visual nodes in neurotypicals. Our study shows that ASD are accompanied by atypical organization of structural covariance networks by means of a decreased centrality of regions relevant for social and sensorimotor processing. These findings provide further evidence for the altered network-level connectivity model of ASD.     

胺碘酮联合美托洛尔治疗老年冠心病

目的探讨胺碘酮联合美托洛尔治疗老年冠心病的临床效果。方法将我院于2013年1月~2014年1月收治的156例老年冠心病患者列为研究对象,将其随机平分,观察组给予常规药物加胺碘酮联合美托洛尔口服;对照组给予常规药物加胺碘酮口服,6个月后对较分析其心绞痛、心律失常的改善情况。结果观察组室性心绞痛、心律失常的治疗有效率均明显大于对照组,差异显著(P0.05),具有统计学意义。结论胺碘酮联合美托洛尔治疗老年冠心病效果比单用胺碘酮疗效好,差异显著。     

In vivo observation of quadrupolar splitting in 39K magnetic resonance spectroscopy of human muscle tissue

The purpose of this work was to explore the origin of oscillations of the T^*₂ decay curve of ³⁹K observed in studies of ³⁹K magnetic resonance imaging of the human thigh. In addition to their magnetic dipole moment, spin‐³/₂ nuclei possess an electric quadrupole moment. Its interaction with non‐vanishing electrical field gradients leads to oscillations in the free induction decay and to splitting of the resonance. All measurements were performed on a 7T whole‐body MRI scanner (MAGNETOM 7T, Siemens AG, Erlangen, Germany) with customer‐built coils. According to the theory of quadrupolar splitting, a model with three Lorentzian‐shaped peaks is appropriate for ³⁹K NMR spectra of the thigh and calf. The frequency shifts of the satellites depend on the angle between the calf and the static magnetic field. When the leg is oriented parallel to the static magnetic field, the satellites are shifted by about 200 Hz. In the thigh, rank‐2 double quantum coherences arising from anisotropic quadrupolar interaction are observed by double‐quantum filtration with magic‐angle excitation. In addition to the spectra, an image of the thigh with a nominal resolution of (16 × 16 × 32) mm³ was acquired with this filtering technique in 1:17 h. From the line width of the resonances, ³⁹K transverse relaxation time constants T^*_{2, fast} = (0.51 ± 0.01) ms and T^*_{2, slow} = (6.21 ± 0.05) ms for the head were determined. In the thigh, the left and right satellite, both corresponding to the short component of the transverse relaxation time constant, take the following values: T^*_{2, fast} = (1.56 ± 0.03) ms and T^*_{2, fast} = (1.42 ± 0.03) ms. The centre line, which corresponds to the slow component, is T^*₂, _slow = (9.67 ± 0.04) ms. The acquisition time of the spectra was approximately 10 min. Our results agree well with a non‐vanishing electrical field gradient interacting with ³⁹K nuclei in the intracellular space of muscle tissue. Copyright © 2016 John Wiley & Sons, Ltd.     

31P solid-state NMR based monitoring of permeation of cell penetrating peptides into skin

The main objective of the current study was to investigate penetration of cell penetrating peptides (CPPs: TAT, R₈, R₁₁, and YKA) through skin intercellular lipids using ³¹P magic angle spinning (MAS) solid-state NMR. In vitro skin permeation studies were performed on rat skin, and sections (0–60, 61–120, and 121–180 μm) were collected and analyzed for ³¹P NMR signal. The concentration-dependent shift of 0, 25, 50, 100, and 200 mg/ml of TAT on skin layers, diffusion of TAT, R₈, R₁₁, and YKA in the skin and time dependent permeation of R₁₁ was measured on various skin sections using ³¹P solid-state NMR. Further, CPPs and CPP-tagged fluorescent dye encapsulate liposomes (FLip) in skin layers were tagged using confocal microscopy. The change in ³¹P NMR chemical shift was found to depend monotonically on the amount of CPP applied on skin, with saturation behavior above 100 mg/ml CPP concentration. R₁₁ and TAT caused more shift in solid-state NMR peaks compared to other peptides. Furthermore, NMR spectra showed R₁₁ penetration up to 180 μm within 30 min. The results of the solid-state NMR study were in agreement with confocal microscopy studies. Thus, ³¹P solid-state NMR can be used to track CPP penetration into different skin layers.