Identifying characteristic features of the retinal and choroidal vasculature in choroideremia using optical coherence tomography angiography.

PurposeUsing optical coherence tomography angiography (OCTA) to investigate the area with flow in the superficial retinal vessel network (SVRN) and choriocapillaris (CC) layer among male subjects with choroideremia (CHM), female carriers, and normal controls to identify vascular changes.Patients and methodsImages of SRVN and CC layer were acquired in 9 affected males, 5 female carriers, and 14 age- and gender-matched controls using the Angiovue software of the RTVue XR Avanti.ResultsThe mean age was 33 years for affected male CHM patients (median 30 years), 46 years for female carriers (median 53 years), and 39 years for controls (median 38.5). Mean SRVN area±SD in subjects with CHM was 12.93±2.06 mm2, in carrier subjects 15.36±0.60 mm2, and in controls 15.30±1.35 mm2 (P<0.01). The mean CC area±SD with flow was 6.97±5.26 mm2 in CHM subjects, 21.65±0.17 mm2 in carriers and 21.36±0.76 mm2 in controls (P<0.01). SRVN and CC area with flow showed a negative correlation in CHM subjects with the age (r=-0.86; P<0.003 and r=-0.77; P<0.01, respectively). CC area with flow had a positive correlation with SRVN (r=0.83, P<0.001). Overall, visual acuity had a negative correlation with SRVN and CC area with flow (r=-0.67, P<0.001 and r=-0.57, P<0.002, respectively). CONCLUSIONS: This is the first study to highlight changes in the SRVN in CHM subjects. OCTA detected a reduced area with flow in both retinal and choroidal circulations, and may be a useful tool for monitoring natural history and disease progression in forthcoming clinical trials.

Ferutinin as a Ca(2+) complexone: lipid bilayers, conductometry, FT-IR, NMR studies and DFT-B3LYP calculations.

Calcium ionophoretic properties of ferutinin were re-evaluated in solvent-containing bilayer lipid membranes. The slopes of conductance-concentration curves suggest that in the presence of a solvent in the membrane the majority of complexes appear to consist of a single terpenoid molecule bound to one Ca ion. By contrast, the stoichiometry of ferutinin-Ca(2+) complexes in acetone determined using the conductometric method was 2 : 1. While the cation-cation selectivity of ferutinin did not change, the cation-anion selectivity slightly decreased in solvent containing membranes. FT-IR and NMR data together with DFT calculations at the B3LYP/6-31G(d) level of theory indicate that in the absence of Ca ions ferutinin molecules are hydrogen-bonded at the phenol hydroxyl groups. The variations of absorption assigned to -OH and -C-O stretching mode suggest that ferutinin interacts strongly with Ca ions via the hydroxyl group of ferutinol and carboxyl oxygen of the complex ether bond. The coordination through the carbonyl group of ferutinin was demonstrated by theoretical calculations. Taken together, ferutinin molecules form H-bonded dimers, while complexation of Ca(2+) by ferutinin ruptures this hydrogen bond due to spatial re-orientation of the ferutinin molecules from parallel to antiparallel alignment.

Synthesis, antifeedant activity against Coleoptera and 3D QSAR study of alpha-asarone derivatives.

For the first time, a set of 56 compounds representing structural derivatives of naturally occurring alpha-asarone as an antifeedants against stored product pests Sitophilus granarius L., Trogoderma granarium Ev., and Tribolium confusum Duv., were subjected to the 3D QSAR studies. Three-dimensional quantitative structure-activity relationships (3D-QSAR) for 56 compounds, including 15 newly synthesized, were performed using comparative molecular field analysis s-CoMFA and SOM-CoMSA techniques. QSAR was conducted based on a combination of biological activity (against Coleoptera larvae and beetles) and various geometrical, topological, quantum-mechanical, electronic, and chromatographic descriptors. The CoMSA formalism coupled with IVE (CoMSA-IVE) allowed us to obtain highly predictive models for Trogoderma granarium Ev. larvae. We have found that this novel method indicates a clear molecular basis for activity and lipophilicity. This investigation will facilitate optimization of the design of new potential antifeedants.

Reconstructing foveal pit morphology from optical coherence tomography imaging.

AIM: The aim of this study was to describe an automated method for extracting quantitative measures of foveal morphology from optical coherence tomography (OCT) images of the human retina. METHODS: We performed a methodological study and retrospective investigation of selected cases. Sixty-five human subjects were included: 61 healthy subjects and four female carriers of blue-cone monochromacy (BCM). Thickness data from B-scans traversing the foveal pit were fitted to a mathematical model designed to capture the contour of the foveal surface. From this model, various metrics of foveal morphology were extracted (pit depth, diameter and slope). RESULTS: Mathematical descriptions of foveal morphology enabled quantitative and objective evaluation of foveal dimensions from archived OCT data sets. We found a large variation in all aspects of the foveal pit (depth, diameter and slope). In myopes and BCM carriers, foveal pits were slightly less deep and had a more shallow slope, although these differences were not significant. CONCLUSIONS: Offline analysis of OCT data sets enables quantitative assessment of foveal morphology. The algorithm works on the Stratus and Cirrus macular thickness protocols, as well as the Spectralis and Bioptigen radial-line scan protocols, and can be objectively applied to existing data sets. These metrics will be useful in following changes associated with diseases such as retinopathy of prematurity and high myopia, as well as in studying normal postnatal development of the human fovea.

Synthesis and hypolipidemic and antiplatelet activities of alpha-asarone isomers in humans (in vitro), mice (in vivo), and rats (in vivo).

A series of alpha-asarone isomers was synthesized and investigated for their hypolipidemic and antiplatelet activity. Considering the hypolipidemic activity in rats at a dose of 80 mg/kg/day, some isomers were more potent than clofibrate at 150 mg/kg. Compound 3 was one of the most active agents elevating the HDL cholesterol level by 56% and lowering the LDL cholesterol level by 46.8% in rats after 7 days of administration. The activities of the platelet aggregation test in vitro were significant but lower than those of the reference substances (indomethacine and acetylsalicylic acid). In the pulmonary thromboembolic in vivo test in mice, two compounds (alpha-asarone (6) and compound 4) produced significant antithrombotic effects at 100 mg/kg, namely 44% and 52% protection against lung microembolia, respectively. alpha-Asarone derivatives form a new group of potential hypolipidemic and/or antithrombotic agents. The compounds 3, 4, and 6 may serve as lead substances whose structural modifications may result in original drugs.