Benefit of anti-HER2-coated paclitaxel-loaded immuno-nanoparticles in the treatment of disseminated ovarian cancer: Therapeutic efficacy and biodistribution in mice.

The benefit of polymeric immuno-nanoparticles (NPs-Tx-HER), consisting of paclitaxel (Tx)-loaded nanoparticles coated with anti-HER2 monoclonal antibodies (Herceptin, trastuzumab), in cancer treatment was assessed in a disseminated xenograft ovarian cancer model induced by intraperitoneal inoculation of SKOV-3 cells overexpressing HER2 antigens. The study was focused on the evaluation of therapeutic efficacy and biodistribution of NPs-Tx-HER compared to other Tx formulations. The therapeutic efficacy was determined by two methods: bioluminescence imaging and survival rate. The treatment regimen consisted in an initial dose of 20mg/kg Tx administered as 10mg/kg intravenously (IV) and 10mg/kg intraperitonealy (IP), followed by five alternative IP and IV injections of 10mg/kg Tx every 3 days. The bioluminescence study has clearly shown the superior anti-tumor activity of NPs-Tx-HER compared to free Tx. As a confirmation of these results, a significantly longer survival of mice was observed for NPs-Tx-HER treatment compared to free Tx, Tx-loaded nanoparticles coated with an irrelevant mAb (Mabthera, rituximab) or Herceptin alone, indicating the potential of immuno-nanoparticles in cancer treatment. The biodistribution pattern of Tx was assessed on healthy and tumor bearing mice after IV or IP administration. An equivalent biodistribution profile was observed in healthy mice for Tx encapsulated either in uncoated nanoparticles (NPs-Tx) or in NPs-Tx-HER. No significant difference in Tx biodistribution was observed after IV or IP injection, except for a lower accumulation in the lungs when NPs were administered by IP. Encapsulated Tx accumulated in the organs of the reticulo-endothelial system (RES) such as the liver and spleen, whereas free Tx had a non-specific distribution in all tested organs. Compared to free Tx, the single dose injection (IV or IP) of encapsulated Tx in mice bearing tumors induced a higher tumor accumulation. However, no difference in overall tumor accumulation between NPs-Tx-HER and NPs-Tx was observed. In conclusion, the encapsulation of Tx into NPs-Tx-HER immuno-nanoparticles resulted in an improved efficacy of drug in the treatment of disseminated ovarian cancer overexpressing HER2 receptors.

Nuclear magnetic resonance

This article reviews the principles and methods of nuclear magnetic resonance spectroscopy, and gives examples of applications carried out at ourFacility, which illustrate the capabilities of the technique.

Thermal and magnetic field-induced martensite-austenite transition in Ni50.3Mn35.3Sn14.4 ribbons

Thermal and field-induced martensite-austenite transition was studied in melt spun Ni50.3Mn35.3Sn14.4 ribbons. Its distinct highly ordered columnarlike microstructure normal to ribbon plane allows the direct observation of critical fields at which field-induced and highly hysteretic reverse transformation starts (H=17kOe at 240K), and easy magnetization direction for austenite and martensite phases with respect to the rolling direction. Single phase L21 bcc austenite with TC of 313K transforms into a 7M orthorhombic martensite with thermal hysteresis of 21K and transformation temperatures of MS=226K, Mf=218K, AS=237K, and Af=244K

Magnetism of isolated Mn12 single-molecule magnets detected by magnetic circular dichroism: Observation of spin tunneling with a magneto-optical technique

We report magnetic and magneto-optical measurements of two Mn12 single-molecule magnet derivatives isolated in organic glasses. Field-dependent magnetic circular dichroism (MCD) intensity curves (hysteresis cycles) are found to be essentially identical to superconducting quantum interference device magnetization results and provide experimental evidence for the potential of the optical technique for magnetic characterization. Optical observation of magnetic tunneling has been achieved by studying the decay of the MCD signal at weak applied magnetic field

Nanoparticles in SiH4-Ar plasma: Modelling and comparison with experimental data

Experimental and theoretical investigations for growth of silicon nanoparticles (4 to 14 nm) in radio frequency discharge were carried out. Growth processes were performed with gas mixtures of SiH4 and Ar in a plasma chemical reactor at low pressure. A distinctive feature of presented kinetic model of generation and growth of nanoparticles (compared to our earlier model) is its ability to investigate small"critical" dimensions of clusters, determining the rate of particle production and taking into account the influence of SiH2 and Si2Hm dimer radicals. The experiments in the present study were extended to high pressure (≥20 Pa) and discharge power (≥40 W). Model calculations were compared to experimental measurements, investigating the dimension of silicon nanoparticles as a function of time, discharge power, gas mixture, total pressure, and gas flow.

Asymmetric giant magnetoresistance in Co10Cu90 magnetic granular alloys

We have observed a type of giant magnetoresistance (GMR) in magnetic granular Co10Cu90 alloys. The asymmetric GMR depends strongly on the size of magnetic Co particles, which exhibit superparamagnetic behavior at given measured temperature. The asymmetric GMR points to a metastable state that develops when the sample is field-cooled, which is lost after recycling. We propose that high-field cooling produces more effective parallel alignment of small unblocked Co particle moments and interfacial magnetizations, which contributes to the further decrease of the resistance in comparison with the samples zero-field-cooled, and then applied to the same field.

A pipeline approach with spatial information for segmenting multiple sclerosis lesions on brain magnetic resonance imaging

Background: Conventional magnetic resonance imaging (MRI) techniques are highly sensitive to detect multiple sclerosis (MS) plaques, enabling a quantitative assessment of inflammatory activity and lesion load. In quantitative analyses of focal lesions, manual or semi-automated segmentations have been widely used to compute the total number of lesions and the total lesion volume. These techniques, however, are both challenging and time-consuming, being also prone to intra-observer and inter-observer variability.Aim: To develop an automated approach to segment brain tissues and MS lesions from brain MRI images. The goal is to reduce the user interaction and to provide an objective tool that eliminates the inter- and intra-observer variability.Methods: Based on the recent methods developed by Souplet et al. and de Boer et al., we propose a novel pipeline which includes the following steps: bias correction, skull stripping, atlas registration, tissue classification, and lesion segmentation. After the initial pre-processing steps, a MRI scan is automatically segmented into 4 classes: white matter (WM), grey matter (GM), cerebrospinal fluid (CSF) and partial volume. An expectation maximisation method which fits a multivariate Gaussian mixture model to T1-w, T2-w and PD-w images is used for this purpose. Based on the obtained tissue masks and using the estimated GM mean and variance, we apply an intensity threshold to the FLAIR image, which provides the lesion segmentation. With the aim of improving this initial result, spatial information coming from the neighbouring tissue labels is used to refine the final lesion segmentation.Results:The experimental evaluation was performed using real data sets of 1.5T and the corresponding ground truth annotations provided by expert radiologists. The following values were obtained: 64% of true positive (TP) fraction, 80% of false positive (FP) fraction, and an average surface distance of 7.89 mm. The results of our approach were quantitatively compared to our implementations of the works of Souplet et al. and de Boer et al., obtaining higher TP and lower FP values.Conclusion: Promising MS lesion segmentation results have been obtained in terms of TP. However, the high number of FP which is still a well-known problem of all the automated MS lesion segmentation approaches has to be improved in order to use them for the standard clinical practice. Our future work will focus on tackling this issue.

Investigation of high-resolution functional magnetic resonance imaging by means of surface and array radiofrequency coils at 7 T.

In this investigation, high-resolution, 1x1x1-mm(3) functional magnetic resonance imaging (fMRI) at 7 T is performed using a multichannel array head coil and a surface coil approach. Scan geometry was optimized for each coil separately to exploit the strengths of both coils. Acquisitions with the surface coil focused on partial brain coverage, while whole-brain coverage fMRI experiments were performed with the array head coil. BOLD sensitivity in the occipital lobe was found to be higher with the surface coil than with the head array, suggesting that restriction of signal detection to the area of interest may be beneficial for localized activation studies. Performing independent component analysis (ICA) decomposition of the fMRI data, we consistently detected BOLD signal changes and resting state networks. In the surface coil data, a small negative BOLD response could be detected in these resting state network areas. Also in the data acquired with the surface coil, two distinct components of the positive BOLD signal were consistently observed. These two components were tentatively assigned to tissue and venous signal changes.

Fate of Hydrophilic Nanoparticles in Biological Environments

The nanoparticles developed are based on chitosan, a biocompatible and biodegradable polysaccharide. The chitosan nanoparticles are formed in an entirely water-based process by electrostatic interactions with other biocompatible molecules. As a prerequisite to understand the fate of such nanoparticles in cells, comprehensive characterization and stability studies serve to identify quantitatively the impact of the raw material characteristics and preparation conditions on the nanoparticle characteristics. Methods included H-1 NMR spectroscopy, dilution viscometry, particle size analysis and electron microscopy. Cytotoxicity and cell uptake experiments on RAW 264.7 murine macrophages and p23 murine endothelial cells were performed to investigate the correlation with nanoparticle characteristics and effect of surface decoration with alginate. Cytotoxicity was assessed by the MTT survival test; cell uptake was monitored by fluorescent microscopy using labeled polymers.

Phosphorus analysis in soil under herbaceous perennial leguminous cover by nuclear magnetic spectroscopy

The availability and the reserves of organic phosphorus are controlled by its mineralization rate and are also influenced by changes in soil management. The objective of this study was to evaluate the influence of soil covering with different leguminous plant on soil organic P by 31P-NMR spectroscopy. Alkaline soil extracts were obtained from two depths (0-5 and 5-10 cm) of an Ultisol cultivated with herbaceous perennial leguminous plants (Arachis pintoi, Pueraria phaseoloides, Macroptilium atropurpureum). In an adjacent area, samples of the same soil cover with a secondary tropical forest and grass (Panicum maximum) were also collected. The leguminous management was divided into with removal and without removal of shoot parts after cut on soil surface. Phosphate monoesters are the dominant P species in all soil samples and P diesters accumulated on the superficial layer of secondary forest soil. The P amount of this fraction is higher for the legume covered soil when compared with the grass covered soil. The permanence of leguminous plants on the topsoil after the cut promoted an increase in P diester/P monoester ratios. These findings can be accounted for an enhancement of P availability to plants in soils cultivated with leguminous plants.

Détection des lésions focales hépatiques malignes. Comparaison de l'échographie, de la porto-tomodensitométrie, de la tomodensitométrie tardive et de l'imagerie par résonance magnétique [Detection of malignant focal hepatic lesions. Comparison of ultrasonography, computerized tomography during arterial portography, delayed computerized tomography and magnetic resonance imaging]

AIMS: This study was performed to compare the sensitivity of ultrasonography, computerized tomography during arterial portography, delayed computerized tomography, and magnetic resonance imaging to detect focal liver lesions. Forty three patients with primary or secondary malignant liver lesions were studied prior to surgical intervention. METHODS: The results of the imaging studies were compared with intraoperative examination of the liver, intraoperative ultrasonography and pathology results (29 patients). In the non-operated (14 patients) group, we compared the number of lesions detected by each technique. RESULTS: One hundred and forty six lesions were detected. There was 84% sensitivity with computerized tomography during arterial portography, 61.3% with delayed scan, 63.3% with magnetic resonance imaging and 51% with ultrasonography in operated patients. In patients who did not undergo surgery, magnetic resonance imaging was more sensitive in detecting lesions. CONCLUSIONS: In operated and non-operated patients series, CT during arterial portography had the highest sensitivity, but magnetic resonance imaging had the most consistent overall results.

Detecting the oxidative reactivity of nanoparticles: a new protocol for reducing artifacts

Understanding the oxidative reactivity of nanoparticles (NPs; <100 nm) could substantially contribute to explaining their toxicity. We attempted to refine the use of 2′7-dichlorodihydrofluorescein (DCFH) to characterize NP generation of reactive oxygen species (ROS). Several fluorescent probes have been applied to testing oxidative reactivity, but despite DCFH being one of the most popular for the detection of ROS, when it has been applied to NPs there have been an unexplainably wide variability in results. Without a uniform methodology, validating even robust results is impossible. This study, therefore, identified sources of conflicting results and investigated ways of reducing occurrence of artificial results. Existing techniques were tested and combined (using their most desirable features) to form a more reliable method for the measurement of NP reactivity in aqueous dispersions. We also investigated suitable sample ranges necessary to determine generation of ROS. Specifically, ultrafiltration and time-resolved scan absorbance spectra were used to study possible optical interference when using high sample concentrations. Robust results were achieved at a 5 µM DCFH working solution with 0.5 unit/mL horseradish peroxidase (HRP) dissolved in ethanol. Sonication in DCFH-HRP working solution provided more stable data with a relatively clean background. Optimal particle concentration depends on the type of NP and in general was in the µg/mL range. Major reasons for previously reported conflicting results due to interference were different experimental approaches and NP sample concentrations. The protocol presented here could form the basis of a standardized method for applying DCFH to detect generation of ROS by NPs.

Nanoparticles for fingermark detection: an insight into the reaction mechanism

This publication presents one of the first uses of silicon oxide nanoparticles to detect fingermarks. The study is not confined to showing successful detection of fingermarks, but is focused on understanding the mechanisms involved in the fingermark detection process. To gain such an understanding, various chemical groups are grafted onto the nanoparticle surface, and parameters such as the pH of the solutions or zeta potential are varied to study their influence on the detection. An electrostatic interaction has been the generally accepted hypothesis of interaction between nanoparticles and fingermarks, but the results of this research challenge that hypothesis, showing that the interaction is chemically driven. Carboxyl groups grafted onto the nanoparticle surfaces react with amine groups of the fingermark secretion. This formation of amide linkage between carboxyl and amine groups has further been favoured by catalyzing the reaction with a compound of diimide type. The research strategy adopted here ought to be applicable to all detection techniques using nanoparticles. For most of them the nature of the interaction remains poorly understood.

A review of atlas-based segmentation for magnetic resonance brain images.

Normal and abnormal brains can be segmented by registering the target image with an atlas. Here, an atlas is defined as the combination of an intensity image (template) and its segmented image (the atlas labels). After registering the atlas template and the target image, the atlas labels are propagated to the target image. We define this process as atlas-based segmentation. In recent years, researchers have investigated registration algorithms to match atlases to query subjects and also strategies for atlas construction. In this paper we present a review of the automated approaches for atlas-based segmentation of magnetic resonance brain images. We aim to point out the strengths and weaknesses of atlas-based methods and suggest new research directions. We use two different criteria to present the methods. First, we refer to the algorithms according to their atlas-based strategy: label propagation, multi-atlas methods, and probabilistic techniques. Subsequently, we classify the methods according to their medical target: the brain and its internal structures, tissue segmentation in healthy subjects, tissue segmentation in fetus, neonates and elderly subjects, and segmentation of damaged brains. A quantitative comparison of the results reported in the literature is also presented.