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1.
Methods Mol Biol ; 1339: 377-86, 2015.
Article in English | MEDLINE | ID: mdl-26445805

ABSTRACT

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.


Subject(s)
Atherosclerosis/diagnostic imaging , Fluorodeoxyglucose F18 , Molecular Imaging/methods , Positron-Emission Tomography , Radiopharmaceuticals , Animals , Atherosclerosis/genetics , Disease Models, Animal , Equipment Design , Genetic Predisposition to Disease , Image Interpretation, Computer-Assisted , Mice, Transgenic , Molecular Imaging/instrumentation , Multimodal Imaging , Positron-Emission Tomography/instrumentation , Predictive Value of Tests , Reproducibility of Results , Tomography, X-Ray Computed
2.
Science ; 346(6214): 1234-8, 2014 Dec 05.
Article in English | MEDLINE | ID: mdl-25477463

ABSTRACT

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.


Subject(s)
Blood Platelets/immunology , Inflammation/immunology , Neutrophils/immunology , Platelet Activation , Thrombosis/immunology , Animals , Blood Circulation , Cell Movement , Cell Polarity , Endothelium, Vascular/immunology , Inflammation/blood , Male , Membrane Glycoproteins , Mice , Mice, Inbred C57BL , Signal Transduction , Venules/immunology
3.
Chemistry ; 20(50): 16662-71, 2014 Dec 08.
Article in English | MEDLINE | ID: mdl-25319949

ABSTRACT

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.


Subject(s)
Contrast Media/chemistry , Ferric Compounds/chemistry , Magnetite Nanoparticles/chemistry , Phosphatidylcholines/chemistry , Animals , Cell Line , Contrast Media/pharmacokinetics , Ferric Compounds/blood , Magnetic Resonance Imaging , Male , Mice, Inbred C57BL , Micelles , Phosphatidylcholines/blood , Rats , Rats, Wistar
4.
PLoS One ; 9(3): e91996, 2014.
Article in English | MEDLINE | ID: mdl-24637581

ABSTRACT

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.


Subject(s)
Asthma/genetics , Gene Silencing , RNA, Small Interfering/genetics , Suppressor of Cytokine Signaling Proteins/genetics , Animals , Asthma/diagnosis , Asthma/immunology , Asthma/metabolism , Collagen/metabolism , Cytokines/genetics , Cytokines/metabolism , Disease Models, Animal , Gene Expression Profiling , Gene Expression Regulation , Gene Knockdown Techniques , Gene Transfer Techniques , Immunity, Humoral , Lung/immunology , Lung/metabolism , Lung/pathology , Male , Mice , MicroRNAs/genetics , Phenotype , RNA, Small Interfering/administration & dosage , Respiratory Mucosa/metabolism , Respiratory Mucosa/pathology , Signal Transduction , Suppressor of Cytokine Signaling 3 Protein , Suppressor of Cytokine Signaling Proteins/metabolism , X-Ray Microtomography
5.
Phys Med Biol ; 57(12): 3963-80, 2012 Jun 21.
Article in English | MEDLINE | ID: mdl-22647928

ABSTRACT

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.


Subject(s)
Image Processing, Computer-Assisted/instrumentation , Phantoms, Imaging , Positron-Emission Tomography/instrumentation , Automation
6.
J Drug Educ ; 41(2): 183-202, 2011.
Article in English | MEDLINE | ID: mdl-21888000

ABSTRACT

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,


Subject(s)
Substance-Related Disorders/epidemiology , Adolescent , Adult , Alcohol Drinking/epidemiology , Amphetamines , Cluster Analysis , Dancing , Designer Drugs , Female , Hallucinogens , Humans , Interviews as Topic , Male , Marijuana Smoking/epidemiology , Music , Risk Factors , Smoking/epidemiology , Spain/epidemiology , Surveys and Questionnaires
7.
Subst Use Misuse ; 43(7): 919-35, 2008.
Article in English | MEDLINE | ID: mdl-18570025

ABSTRACT

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.


Subject(s)
Heroin Dependence/diagnosis , Psychiatric Status Rating Scales/statistics & numerical data , Adult , Data Collection/statistics & numerical data , Factor Analysis, Statistical , Female , Heroin Dependence/epidemiology , Heroin Dependence/psychology , Humans , Male , Models, Statistical , Principal Component Analysis , Probability , Psychometrics , Reproducibility of Results , Severity of Illness Index , Spain/epidemiology
8.
Adicciones ; 20(1): 19-26, 2008.
Article in Spanish | MEDLINE | ID: mdl-18299778

ABSTRACT

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.


Subject(s)
Attitude to Health , Buprenorphine/therapeutic use , Narcotics/therapeutic use , Substance-Related Disorders/rehabilitation , Humans , Patient Satisfaction , Pilot Projects , Residential Treatment , Stereotyping
10.
Arch. med. deporte ; 21(101): 215-220, mayo-jun. 2004. ilus, tab, graf
Article in Es | IBECS | ID: ibc-34331

ABSTRACT

El patinaje de velocidad es un deporte reconocido internacionalmente, que cuenta con un número de practicantes que aumenta continuamente. A pesar de ello, se trata de un deporte poco conocido desde el punto de vista médico, siendo muy escasos los trabajos científicos que lo abordan. En el presente trabajo pretendemos valorar el nivel de condición física de un grupo de patinadores de alto nivel, así como determinar las implicaciones funcionales relacionadas con la economía de carrera, que se derivan de la posición que ocupa el patinador dentro del grupo. Fueron seguidos 10 patinadores, realizándoles un reconocimiento médico-deportivo completo, así como pruebas de esfuerzo tanto de laboratorio como de campo. Éstas se concretaron a tres intensidades diferentes (80 por ciento de la velocidad umbral, velocidad umbral y velocidad máxima), y en cada una de ellas, en las posiciones delantera y trasera. Al 80 por ciento de la velocidad umbral se obtuvieron unos valores medios de consumo de oxígeno de 37 ml/kg. min yendo delante frente a 31 ml/kg.min en la posición de detrás. A velocidad umbral las cifras medias obtenidas fueron respectivamente de 62 frente a 53 ml/kg.min, mientras que a velocidad máxima estos valores resultaron en 74 frente a 64 ml/kg. min. En función a las cifras señaladas observamos mayores consumos de oxígeno, para las tres intensidades consideradas, en la posición de delante, siendo estas diferencias menores en el caso de los patinadores de mayor nivel competitivo. Estimamos que este hecho ha de ser tenido en cuenta a la hora de establecer las intensidades y estrategias en los entrenamientos y competiciones, pudiendo ser un parámetro importante en la consecución del éxito deportivo en este deporte (AU)


The on-line skating is internationally a grateful sport that counts with a number of practitioners that increases of continuous. In spite of it, it is a not very well-known sport from the medial point of view, being very scarce the scientific papers that approach the same one. The aim of this paper is to value the level of physical condition of a high level skaters group, as well as to determine the functional implications related with the recing economy that are derived of the postition tha the skater occupies inside the group. 10 skaters were continued carrying out them a complete medical-sport recognition as well as you prove of effort so much of laboratoy as of field. These were summed up to three different intensities (80% of the speed threshold, speed threshold and maximum speed), and in each one of them, in the positons leading and back (...) (AU)


Subject(s)
Adolescent , Adult , Male , Humans , Skating , Physical Conditioning, Human , Oxygen Consumption/physiology , Physical Exertion/physiology , Heart Rate/physiology , Energy Metabolism/physiology
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