Phosphatidylcholine-coated iron oxide nanomicelles for in vivo prolonged circulation time with an antibiofouling protein corona.

We report the synthesis of micellar phosphatidylcholine-coated superparamagnetic iron oxide nanoparticles as a new long circulation contrast agents for magnetic resonance imaging. Oleic acid-coated Fe3 O4 nanoparticles were first prepared through thermal degradation and then encapsulated into small clusters with a phosphatidylcholine coating to obtain hydrophilic nanomicelles. A thorough characterization confirmed the chemical nature of the coating and the excellent colloidal stability of these nanomicelles in aqueous media. Magnetization and relaxivity properties proved their suitability as magnetic resonance imaging (MRI) contrast agent and in vitro cell viability data showed low toxicity. Vascular lifetime and elimination kinetics in the liver were assessed by blood relaxometry and by in vivo MRI in rats and compared with "control" particles prepared with a polyethylene glycol derivative. These micellar particles had a lifetime in blood of more than 10 h, much longer than the control nanoparticles (≈2 h), which is remarkable considering that the coating molecule is a small biocompatible zwitterionic phospholipid. The protein corona was characterized after incubation with rat serum at different times by high-throughput proteomics, showing a higher proportion of bound apolipoproteins and other dysopsonins for the phosphatidylcholine particles. The antibiofouling properties of this corona and its resistance to the adsorption of proteins corroborate the observed enhanced stability and prolonged systemic circulation.

[Emergent dimensions for the construction of an opiate substitute treatment perception scale]. / Dimensiones emergentes para la creación de una escala de percepción del tratamiento con sustitutivos opiáceos.

The measurement of perception and satisfaction with opiate substitute treatment programmes has concentrated mainly on evaluating the properties of the service offered at treatment centres. Beyond the health-care context, these programmes need to become part of the patient's personal and social life for them to be followed. The purpose of this work is to offer a theoretical frame of reference for the construction of a scale for integral measurement of patient perception of opiate substitute treatments. A sample of 18 outpatient and residential patients in a buprenorphine pilot study, transferred from a methadone treatment programme, who showed indications of abandoning treatment, was given a semi-structured interview. The data analysis was done based on the Grounded Theory, and the dimensions were coded and material triangulated by three specialized analysts. The results show that patient perception of treatment with substitutes is aligned in five main dimensions, value to health, adaptation to daily life, stigma, treatment withdrawal and perceived effectiveness. These results are discussed and compared to those found in specialised literature.

In Vivo ¹8F-FDG-PET Imaging in Mouse Atherosclerosis.

Positron emission tomography (PET) is an important technique in cardiovascular research. Vascular inflammation detected by fluorodeoxyglucose (FDG)-PET has been shown to predict cardiovascular (CV) events independent of traditional risk factors and is also highly associated with overall burden of atherosclerosis. The use of PET imaging in mouse models of atherosclerosis is challenged by the reduced size of the scanned organs. However, the last generation of dedicated PET scanners has an improved spatial resolution (<1 mm) and increased sensitivity allowing those studies to be performed. Here, we describe a procedure to perform FDG-PET experiments in atherosclerosis mouse models, the required equipment for animal handling and imaging, and the tools and procedures for image analysis and validation of the results.

Gene silencing of SOCS3 by siRNA intranasal delivery inhibits asthma phenotype in mice.

Suppresors of cytokine signaling (SOCS) proteins regulate cytokine responses and control immune balance. Several studies have confirmed that SOCS3 is increased in asthmatic patients, and SOCS3 expression is correlated with disease severity. The objective of this study was to evaluate if delivering of SOCS3 short interfering RNA (siRNA) intranasally in lungs could be a good therapeutic approach in an asthma chronic mouse model. Our results showed that intranasal treatment with SOCS3-siRNA led to an improvement in the eosinophil count and the normalization of hyperresponsiveness to methacholine. Concomitantly, this treatment resulted in an improvement in mucus secretion, a reduction in lung collagen, which are prominent features of airway remodeling. The mechanism implies JAK/STAT and RhoA/Rho-kinase signaling pathway, because we found a decreasing in STAT3 phosphorylation status and down regulation of RhoA/Rho-kinase protein expression. These results might lead to a new therapy for the treatment of chronic asthma.

Neutrophils scan for activated platelets to initiate inflammation.

Immune and inflammatory responses require leukocytes to migrate within and through the vasculature, a process that is facilitated by their capacity to switch to a polarized morphology with an asymmetric distribution of receptors. We report that neutrophil polarization within activated venules served to organize a protruding domain that engaged activated platelets present in the bloodstream. The selectin ligand PSGL-1 transduced signals emanating from these interactions, resulting in the redistribution of receptors that drive neutrophil migration. Consequently, neutrophils unable to polarize or to transduce signals through PSGL-1 displayed aberrant crawling, and blockade of this domain protected mice against thromboinflammatory injury. These results reveal that recruited neutrophils scan for activated platelets, and they suggest that the neutrophils' bipolarity allows the integration of signals present at both the endothelium and the circulation before inflammation proceeds.

Twelve automated thresholding methods for segmentation of PET images: a phantom study.

Tumor volume delineation over positron emission tomography (PET) images is of great interest for proper diagnosis and therapy planning. However, standard segmentation techniques (manual or semi-automated) are operator dependent and time consuming while fully automated procedures are cumbersome or require complex mathematical development. The aim of this study was to segment PET images in a fully automated way by implementing a set of 12 automated thresholding algorithms, classical in the fields of optical character recognition, tissue engineering or non-destructive testing images in high-tech structures. Automated thresholding algorithms select a specific threshold for each image without any a priori spatial information of the segmented object or any special calibration of the tomograph, as opposed to usual thresholding methods for PET. Spherical (18)F-filled objects of different volumes were acquired on clinical PET/CT and on a small animal PET scanner, with three different signal-to-background ratios. Images were segmented with 12 automatic thresholding algorithms and results were compared with the standard segmentation reference, a threshold at 42% of the maximum uptake. Ridler and Ramesh thresholding algorithms based on clustering and histogram-shape information, respectively, provided better results that the classical 42%-based threshold (p < 0.05). We have herein demonstrated that fully automated thresholding algorithms can provide better results than classical PET segmentation tools.

Polysubstance use patterns in underground rave attenders: a cluster analysis.

Drug use in mainstream rave parties has been widely documented in a large number of studies. However, not much is known about drug use in underground raves. The purpose of this study is to find out the polysubstance use patterns at underground raves. Two hundred and fifty-two young people between the ages of 18 and 30 who went to underground raves were interviewed. They were given a questionnaire to collect information on drug use at raves. Ravers used a mean of 4.9 different drugs at the last rave they had been to. Over 75% of them used tobacco, alcohol, cannabis, and amphetamine, and over half also used powder ecstasy. Two differentiated use patterns were found: one pattern concentrated more on the use of stimulants and the other on the use of hallucinogens. Underground ravers have a "standard" sociodemographic profile. The use of drugs is much higher than equivalent age group. Higher drug use prevalence than in mainstream rave parties is also observed. Different patterns of use appear which will be necessary to consider in designing preventions and risk reduction strategies,

Validity of the Severity of Dependence Scale (SDS) construct applying the item response theory to a non-clinical sample of heroin users.

AIMS: The purpose of this work is to study the validity of the Severity of Dependence Scale (SDS) construct by applying Rasch models to a non-clinical sample of heroin abusers. SUBJECTS: 982 (73% men) young people 30 years old or under (mean age 25.9 years) participated. All of them were captured from the community in the metropolitan areas of Madrid, Barcelona and Seville, between April 2002 and December 2003. ANALYSIS: Dimensionality of the scale and calibration of items were studied using the Rating Scale model, which is a Rasch-type model. A factorial analysis was also performed to check the dimensionality of the scale. RESULTS: The analysis of fit shows that all the items have infit and outfit values between +/- 2 logits, indicating that the data fit the model and that it may be assumed to be unidimensional. The principal components analysis also showed the existence of a principal factor that explains 52.5% of the variance observed. Item calibration found that they are between +0.89 and -1.04 logits on the scale. CONCLUSION: The results show unidimensional structure of the SDS scale. Item calibration shows they are distributed along the continuum, which must be taken into account when calculating total scores. The study's limitations are noted.