RESUMEN
BACKGROUND: Intracranial atherosclerosis is a common cause of stroke with a high recurrence rate. Haemodynamically significant lesions are associated with a particularly high risk of recurrence. Computational fluid dynamics (CFD) is a tool that has been investigated to identify haemodynamically significant lesions. CFD in the intracranial vasculature benefits from the precedent set by cardiology, where CFD is an established clinical tool. This precedent is particularly important in CFD as models are very heterogenous. There are many decisions-points in the model-creation process, usually involving a trade-off between computational expense and accuracy. OBJECTIVES: This study aimed to review published CFD models in intracranial atherosclerosis and compare them to those used in cardiology. METHODS: A systematic search for all published computational fluid dynamics models applied to intracranial atherosclerosis was performed. Each study was analysed as regards to the different steps in creating a fluid dynamics model and findings were compared with established cardiology CFD models. RESULTS AND CONCLUSION: 38 papers were screened and 12 were included in the final analysis. There were important differences between coronary and intracranial atherosclerosis models in the following areas: area of interest segmented, use of transient models vs steady-state models, boundary conditions, methods for solving the fluid dynamics equations and validation. These differences may be high-yield areas to explore for future research.
Asunto(s)
Angiografía Cerebral , Arterias Cerebrales/diagnóstico por imagen , Circulación Cerebrovascular , Angiografía por Tomografía Computarizada , Arteriosclerosis Intracraneal/diagnóstico por imagen , Angiografía por Resonancia Magnética , Modelos Cardiovasculares , Modelación Específica para el Paciente , Arterias Cerebrales/fisiopatología , Hemodinámica , Humanos , Hidrodinámica , Arteriosclerosis Intracraneal/fisiopatología , Valor Predictivo de las Pruebas , Pronóstico , Interpretación de Imagen Radiográfica Asistida por ComputadorRESUMEN
The flow-induced vibration response of a square cross-sectional cylinder with low mass and damping ratio is analysed using continuous wavelet transforms (CWT) for three representative angles of attack of the cylinder to the incoming flow. The amplitude and frequency responses over a range of flow velocities map out multiple regimes (branches) of oscillation. Analysis of the time-frequency domain for boundary regions between branches using CWT reveals intermittency at the synchronization region boundaries as well as mode competition at branch boundaries. Complementary recurrence analysis shows that periodic dynamical states are interrupted by chaotic bursts in the transition regions around the higher branch at an angle of attack of α = 20° (a new branch first observed by Nemes et al. (2012 J. Fluid Mech.710, 102-130 (doi:10.1017/jfm.2012.353))), supporting the CWT-based frequency-time analysis.This article is part of the theme issue 'Redundancy rules: the continuous wavelet transform comes of age'.
RESUMEN
A series of trans-2'-hydroxyethyl and 2'-acyloxyethyl apovincaminates 4b- f and 7b- f has been synthesized and evaluated for their antioxidant and antiamnesic effects. The new esters were prepared from 4a and 7a ethyl esters or from the corresponding carboxylic acid sodium salt. For starting materials 11a, b, a new stereoselective trans-reduction was elaborated. From the combined results of the data obtained from in vitro and in vivo tests and examination of the metabolism, (3 R,16 S)-2'-hydroxyethyl apovincaminate ( 7b, RGH-10885) was identified as the most promising compound, owing to its potent neuroprotective and antiamnesic activities. The in vivo effectiveness of selected compounds on the cognitive functions was studied in a one-trial passive avoidance task and a water-labyrinth test.
Asunto(s)
Antioxidantes/síntesis química , Fármacos Neuroprotectores/síntesis química , Nootrópicos/síntesis química , Alcaloides de la Vinca/síntesis química , Animales , Antioxidantes/química , Antioxidantes/farmacología , Reacción de Prevención/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Técnicas In Vitro , Peroxidación de Lípido/efectos de los fármacos , Masculino , Aprendizaje por Laberinto , Memoria/efectos de los fármacos , Ratones , Microsomas/efectos de los fármacos , Microsomas/metabolismo , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Nootrópicos/química , Nootrópicos/farmacología , Ratas , Ratas Wistar , Estereoisomerismo , Relación Estructura-Actividad , Alcaloides de la Vinca/química , Alcaloides de la Vinca/farmacologíaRESUMEN
A reversed-phase thin-layer chromatographic method was developed and applied to quantitate the lipophilicity of sparingly water-soluble eburnane alkaloids of therapeutic interest. Our method development included calibration, optimization and validation procedures, using also sets of auxiliary compounds. The log P(TLC) values of five relatively hydrophilic eburnanes were verified by stir-flask studies. The alkaloids were found to have lipophilicity values in the 2.9-4.8 log P(TLC) range. Conclusions on structure-lipophilicity relationships were drawn in terms of ring anellation, character and length of side chain, conformational preferences and moiety-solvent interactions, also supported by molecular mechanics studies.
