白蛋白微球作为肝靶向给药载体的研究

用均匀设计方法和计算机技术筛选了乳化化学交联法制备白蛋白微球的六个因素,十二个水平。优化出最佳制备工艺,制备了平均粒径0.41～0.47μm的白蛋白微球。将此工艺制备的¹²⁵I-白蛋白微球做动物体内研究,结果表明微球iv后主要浓集在肝脏,可达注入总剂量的68%,此微球在靶组织肝脏的变化规律可用二室模型契合。     

Further study on the vascular basis for the reimplantation of the hand amputated through the palm

Summary Based on the anatomic data obtained from earlier studies on the vascular anatomy of the hand, the vascular architecture in the palm of the hand was studied on 60 sides of unembalmed adult upper extremities. Each palm was divided into 64 squares by 8 sagittal and 8 transverse sections. The vascular architecture in these squares and the arterial relations between them were observed and measured by angiography, operative microscopic dissection and computerised three-dimensional reconstruction. According to the pattern of the blood-vessels, the amputated palms can be classified into 4 types. The anatomic basis for the vascular anastomosis in each type is defined. There are three key-areas for the blood-supply of the palm and their significance is discussed. Apart from the 4 types of transversely amputated palms, the repair programe of the blood-vessles in 4 types of common obliquely amputated palms are also discussed.

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Etude complémentaire de l'anatomie vasculaire de la main pour la réimplantation des amputations transpalmaires

Résumé Sur la base de données anatomiques obtenues lors de précédents travaux sur l'anatomie vasculaire de la main, l'architecture vasculaire palmaire a été étudiée sur 60 extrémités supérieures de cadavres d'adultes, non embaumés. Chaque paume a été divisée en 64 carrés par 8 sections sagittales et 8 sections transversales. L'architecture vasculaire à l'intérieur des carrés et les relations artérielles entre eux ont été étudiées et mesurées par angiographie, dissection au microscope opérateur et reconstruction computérisée en 3D. Les paumes amputées ont été regroupées en 4 types d'après la distribution des vaisseaux sanguins. Les données anatomiques concernant les anastomoses vasculaires sont précisées. Il existe trois zones clés pour l'irrigation de la paume. Leur importance quant à l'irrigation de la main est exposée. Outre la division des paumes amputées transversalement en 4 types, le programme de réparation de vaisseaux dans les 4 types d'amputations obliques communes de la paume et aussi discuté.

     

Spherical lesion phantoms for testing the performance of elastography systems

A set of three cubic one-litre phantoms containing spherical simulated lesions was produced for use in comparing lesion detection performance of different elastography systems. The materials employed are known to be stable in heterogeneous configurations regarding geometry and elastic contrast identical with (storage modulus of lesion material) / (storage modulus of background material), and regarding ultrasound and NMR properties. The materials mimic soft tissues in terms of elastic, ultrasound and NMR properties. Each phantom has only one value of elastic contrast (3.3, 4.6 or 5.5) and contains arrays of 1.6 mm, 2 mm, 3 mm and 4 mm diameter spherical simulated lesions. All the spheres of a given diameter are arranged in a regular array with coplanar centres. Elastograms of an array made with ultrasound allow determination of the depth range over which lesions of that diameter and elastic contrast can be detected. Two phantoms are made from agar-plus-gelatin-based materials, and one is made from oil-in-gelatin dispersions. The methods for producing the phantoms are described in detail. Lesion detection performances for two ultrasound systems, both operating at about 7.5 MHz and focused at about 5 cm, were quantified with distinctions between the two systems demonstrated. Neither system was capable of detecting any of the 1.6 mm lesions. Phantoms such as these should be useful in research labs that are refining hardware and/or software for elastography.     

Differential Imaging of Liver Tumors before and after Microwave Ablation with Electrode Displacement Elastography

Liver cancer is a leading cause of cancer-related deaths; however, primary treatment options such as surgical resection and liver transplant may not be viable for many patients. Minimally invasive image-guided microwave ablation (MWA) provides a locally effective treatment option for these patients with an impact comparable to that of surgery for both cancer-specific and overall survival. MWA efficacy is correlated with accurate image guidance; however, conventional modalities such as B-mode ultrasound and computed tomography have limitations. Alternatively, ultrasound elastography has been used to demarcate post-ablation zones, yet has limitations for pre-ablation visualization because of variability in strain contrast between cancer types. This study attempted to characterize both pre-ablation tumors and post-ablation zones using electrode displacement elastography (EDE) for 13 patients with hepatocellular carcinoma or liver metastasis. Typically, MWA ablation margins of 0.5–1.0 cm are desired, which are strongly correlated with treatment efficacy. Our results revealed an average estimated ablation margin inner quartile range of 0.54–1.21 cm with a median value of 0.84 cm. These treatment margins lie within or above the targeted ablative margin, indicating the potential to use EDE for differentiating index tumors and ablated zones during clinical ablations. We also obtained a high correlation between corresponding segmented cross-sectional areas from contrast-enhanced computed tomography, the current clinical gold standard, when compared with EDE strain images, with r² values of 0.97 and 0.98 for pre- and post-ablation regions.     

In vivo X-ray cine-tomography for tracking morphological dynamics

Scientific cinematography using ultrafast optical imaging is a common tool to study motion. In opaque organisms or structures, X-ray radiography captures sequences of 2D projections to visualize morphological dynamics, but for many applications full four-dimensional (4D) spatiotemporal information is highly desirable. We introduce in vivo X-ray cine-tomography as a 4D imaging technique developed to study real-time dynamics in small living organisms with micrometer spatial resolution and subsecond time resolution. The method enables insights into the physiology of small animals by tracking the 4D morphological dynamics of minute anatomical features as demonstrated in this work by the analysis of fast-moving screw-and-nut–type weevil hip joints. The presented method can be applied to a broad range of biological specimens and biotechnological processes.The best method to study morphological changes of anatomic features and physiological processes is to observe their dynamics in 4D, that is, in real time and in 3D space. To achieve this we have developed in vivo X-ray cine-tomography to gain access to morphological dynamics with unrivaled 4D spatiotemporal resolution. This opens the way to a wide range of hitherto inaccessible, systematic investigations of small animals and biological internal processes such as breathing, circulation, digestion (1), reproduction, and locomotion (2).At the micrometer resolution range, state-of-the-art optical imaging techniques can achieve high magnifications to visualize tissues and even individual cells for 4D studies. These methods however are confined to transparent or fluorescent objects, or are limited either by low penetration depth <1 mm or poor time resolution (3). For optically opaque living organisms X-ray imaging methods are highly appropriate due to the penetrating ability of the radiation. Modern synchrotron radiation facilities provide brilliant and partially coherent radiation suitable for high-resolution volume imaging methods such as X-ray computed microtomography (SR-µCT). For static specimens SR-µCT has proven to be a powerful tool to study small animal morphology in 3D (4–6). The benefits of various physical contrast mechanisms, high spatial resolution, and short measuring times, as well as enormous sample throughput compared with laboratory X-ray setups, have led to its widespread use in life sciences.Real-time in vivo X-ray imaging with micrometer spatial resolution was realized so far by recording time sequences of 2D projection radiographs of different organisms (1, 6, 7), providing time information about functional dynamics but losing any information about the third spatial dimension.Recently, 4D in vivo X-ray experiments have been performed to study cell migration in frog embryos (8, 9) using tomographic sequences of a few seconds exposure time per tomogram interrupted by longer nonexposure time slots. In this way the authors followed relatively slow dynamics and morphological changes during embryonic development with 2-µm resolution over total time intervals of several hours. The fastest 4D time series yet reported were realized with a temporal resolution of 0.5 s and spatial resolution of 25 µm (10), applied to a living caterpillar used as test specimen for imaging, but without any analysis of dynamics.In this paper, we demonstrate the quantitative 4D investigation of morphological dynamics by in vivo X-ray 4D cine-tomography, introduced here as the combination of ultrafast SR-µCT and motion analysis procedures. Using this approach allows us to investigate previously inaccessible 3D morphological dynamics in small animals, presently with feature sizes in the micrometer range and with temporal resolution down to a few tens of milliseconds. In the past, ultrafast in vivo imaging was hardly possible for such applications, due to the strongly competing requirements for simultaneous high contrast, high signal-to-noise ratio (SNR), and concurrent low radiation dose, as well as the need for simultaneous high spatial resolution and maximum temporal resolution.In the following we describe how in vivo X-ray 4D cine-tomography meets the above challenges by optimizing image contrast, SNR, and spatial and temporal resolution in the ultrafast SR-µCT system and by establishing a dedicated data analysis pipeline, all within a unified framework (Fig. S1). We demonstrate the potential of the technique by investigating morphological dynamics in fast-moving weevils, focusing here on the exoskeletal joints.     

Two-dimensional multi-level strain estimation for discontinuous tissue

A large number of the strain estimation methods presented in the literature are based on the assumption of tissue continuity that establishes a continuous displacement field. However, in certain locations in the body such as the arteries in vivo scanning may produce displacement fields that are discontinuous between the two walls of the artery. Many of the displacement or strain estimators fail when the displacement fields are discontinuous. In this paper, we present a new 2D multi-level motion or displacement tracking method for accurate estimation of the strain in these situations. The final high-resolution displacement estimate is obtained using two processing steps. The first step involves an estimation of a coarse displacement estimate utilizing B-mode or envelope signals. To reduce computational time, the coarse displacement estimates are obtained starting from down-sampled B-mode pre- and post-compression image pairs using a pyramidal processing approach. The coarse displacement estimate obtained from the B-mode data is used to guide the final 2D cross-correlation computations on radio-frequency (RF) data. Results from finite element simulations and in vivo experimental data demonstrate the feasibility of this approach for imaging tissue with discontinuous displacement fields.     

Derivatives Form Better Lipoxygenase Inhibitors than Piperine: In Vitro and In Silico Study

Piperine is a secondary metabolite of black pepper. Its uses in medicine were already studied. However, its derivatives have not gained considerable attention. In the presented study, the Lipoxygenase (LOX) inhibitory activity of piperine and its derivatives, piperonylic acid, piperic acid, and piperonal have been assessed and compared by enzyme kinetics, ITC and molecular modeling experiments. The presented investigations expressed that all the studied compounds inhibited LOX by binding at its active site. The IC₅₀ values of these compounds were deduced from the kinetics data and found to be 85.79, 43.065, 45.17, and 50.78 μm for piperine, piperonylic acid, piperic acid, and piperonal, respectively. The binding free energies obtained from ITC experiments were −7.47, −8.33, −8.09, and −7.86 kcal/mol for piperine, piperonylic acid, piperic acid, and piperonal, respectively. Similarly, the glide scores obtained for piperine, piperonylic acid, piperic acid, and piperonal were −7.28, −10.32, −10.72, and −9.57 kcal/mol, respectively. The results of ITC and molecular modeling experiments suggested that piperonylic acid and piperonal exhibit stronger binding at the active site than piperine does. From the presented studies, it could be concluded that derivatives of piperine may be of higher significance than piperine for certain medicinal applications, implicating (Ayurvedic) fermented herbal drugs with piperine in them.