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Herance J.R.,Center dImatge Molecular | Gispert J.D.,Institute dAlta Tecnologia PRBB | Abad S.,Center dImatge Molecular | Victor V.M.,University of Valencia | And 3 more authors.
Contrast Media and Molecular Imaging | Year: 2013

Inhaled radioactive CO is currently the tracer of choice for blood volume quantification by positron emission tomography (PET). This measurement is of great interest for several clinical and research applications. However, owing to the short half-life of the radiolabeled CO, it can only be used in centers equipped with a cyclotron. In the present work, we propose an alternative method to label the red blood cells with [18F] in order to obtain blood volume measurements by PET. The use of the radioactive synthon [18F] N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) was evaluated for erythrocyte labeling and PET blood volume imaging. The images provided by [18F]SFB labeled erythrocytes were compared with those obtained with inhaled [11C]CO. Blood volumes obtained with [18F]SFB labeled erythrocytes were similar to those obtained with [11C]CO in all of the evaluated organs with the exception of spleen, which presented lower uptake with this method. Since the [18F]-SFB binds irreversibly to red blood cells, in vivo stability of the radiolabel was higher compared with the [11C]CO method. Additionally, owing to the longer half-life and the shorter positron range of [18F], the image quality was also higher with the [18F]SFB radiolabeled erythrocytes. The labeling of red blood with [18F]SFB represents an advantageous alternative to radioactive CO for blood volume measurement by PET and cardiovascular isotopic imaging. © 2013 John Wiley & Sons, Ltd.


Pujol J.,Institute dAlta Tecnologia PRBB | Pujol J.,CIBER ISCIII | Soriano-Mas C.,Institute dAlta Tecnologia PRBB | Gispert J.D.,Institute dAlta Tecnologia PRBB | And 14 more authors.
Human Brain Mapping | Year: 2011

Obsessive-compulsive disorder (OCD) emerges during childhood through young adulthood coinciding with the late phases of postnatal brain development when fine remodeling of brain anatomy takes place. Previous research has suggested the existence of subtle anatomical alterations in OCD involving focal volume variations in different brain regions including the frontal lobes and basal ganglia. We investigated whether anatomical changes might also involve variations in the shape of the frontobasal region. A total of 101 OCD patients and 101 control subjects were examined using magnetic resonance imaging. A cross-sectional image highly representative of frontal-basal ganglia anatomy was selected in each individual and 25 reliable anatomical landmarks were identified to assess shape changes. A pixel-wise morphing approach was also used to dynamically illustrate the findings. We found significant group differences for overall landmark position and for most individual landmarks delimiting the defined frontobasal region. OCD patients showed a deformation pattern involving shortening of the anterior-posterior dimension of the frontal lobes and basal ganglia, and enlargement of cerebrospinal fluid spaces around the frontal opercula. In addition, we observed significant correlation of brain tissue shape variation with frontal sinus size. Identification of a global change in the shape of the frontobasal region may further contribute to characterizing the nature of brain alterations in OCD. The coincidence of brain shape variations with morphological changes in the frontal sinus indicates a potential association of OCD to late development disturbances, as the frontal sinus macroscopically emerges during the transition between childhood and adulthood. © 2010 Wiley-Liss, Inc.


Berthier M.L.,University of Malaga | Lambon Ralph M.A.,University of Manchester | Pujol J.,Institute dAlta Tecnologia PRBB | Green C.,University of Malaga
Cortex | Year: 2012

Repetition ability is a major criterion for classifying aphasic syndromes and its status is helpful in the determination of the involved neural structures. It is widely assumed that repetition deficits correlate with injury to the left perisylvian core including the arcuate fasciculus (AF). However, descriptions of normal repetition despite damage to the AF or impaired repetition without AF involvement cast doubts on its role in repetition. To explain these paradoxes, we analyse two different aphasic syndromes - in which repetition is selectively impaired (conduction aphasia) or spared (transcortical aphasias) - in light of recent neuroimaging findings. We suggest that the AF and other white matter bundles are the anatomical signatures of language repetition and that individual variability in their anatomy and lateralisation may explain negative cases. © 2011 Elsevier Srl.


Martin R.,Polytechnic University of Valencia | Alvaro M.,Polytechnic University of Valencia | Herance J.R.,Institute dAlta Tecnologia PRBB | Garcia H.,Polytechnic University of Valencia
ACS Nano | Year: 2010

When raw diamond nanoparticles (Dnp, 7 nm average particle size) obtained from detonation are submitted to harsh Fenton-treatment, the resulting material becomes free of amorphous soot matter and the process maintains the crystallinity, reduces the particle size (4 nm average particle size), increases the surface OH population, and increases water solubility. All these changes are beneficial for subsequent Dnp covalent functionalization and for the ability of Dnp to cross cell membranes. Fenton-treated Dnps have been functionalized with thionine and the resulting sample has been observed in HeLa cell nuclei. A triethylammonium-functionalized Dnp pairs electrostatically with a plasmid having the green fluorescent protein gene and acts as gene delivery system permitting the plasmid to cross HeLa cell membrane, something that does not occur for the plasmid alone without assistance of polycationic Dnp. © 2010 American Chemical Society.


Rocha M.,University of Valencia | Herance R.,Institute dAlta Tecnologia PRBB | Rovira S.,University of Valencia | Hernandez-Mijares A.,University of Valencia | Victor V.M.,University of Valencia
Infectious Disorders - Drug Targets | Year: 2012

Sepsis and septic shock are the major causes of death in intensive care units. Oxidative damage to mitochondria is involved in the development of organ dysfunction associated with sepsis. This syndrome is caused by an excessive defensive and inflammatory response characterised by a massive increases of reactive oxygen species (ROS), nitric oxide (NO) and inflammatory cytokines. Under normal circumstances, complex interacting antioxidant defense systems control oxidative stress within mitochondria The consequences of sepsis is a systemic damage to the vascular endothelium, impaired tissue and a compromised whole body respiration, antioxidant depletion and mitochondrial respiratory dysfunction with diminished levels of ATP and O 2 consumption. In general, ROS are essential to the functions of cells and particularly immune cells, but adequate levels of antioxidant defenses are required to protect against the harmful effects of excessive ROS production. This review considers the process of sepsis from a mitochondrial perspective, discussing strategies for the targeted delivery of antioxidants to mitochondria. We will provide a summary of the following areas: the cellular metabolism of ROS and its role in pathophysiological processes such as sepsis; currently available antioxidants and possible reasons for their efficacy and inefficacy in ameliorating oxidative stress-mediated diseases; and recent developments in mitochondria-targeted antioxidants and the future implications for such approaches in patients. © 2012 Bentham Science Publishers.


Garcia-Bou R.,University of Valencia | Rocha M.,University of Valencia | Apostolova N.,University of Valencia | Herance R.,Institute dAlta Tecnologia PRBB | And 2 more authors.
Biochimica et Biophysica Acta - Bioenergetics | Year: 2012

The medical use of nitroglycerin (GTN) is limited by patient tolerance. The present study evaluated the role of mitochondrial Complex I in GTN biotransformation and the therapeutic effect of mitochondrial antioxidants. The development of GTN tolerance (in rat and human vessels) produced a decrease in mitochondrial O2 consumption. Co-incubation with the mitochondria-targeted antioxidant mitoquinone (MQ, 10- 6 mol/L) or with glutathione ester (GEE, 10- 4 mol/L) blocked GTN tolerance and the effects of GTN on mitochondrial respiration and aldehyde dehydrogenase 2 (ALDH-2) activity. Biotransformation of GTN depended on the mitochondria being functionally active, particularly mitochondrial Complex I. Tolerance induced mitochondrial ROS production and oxidative stress, though these effects were not detected in HUVECρ0 cells or Complex I mutant cells. Experiments performed to evaluate Complex I-dependent respiration demonstrated that its inhibition by GTN was prevented by the antioxidants in control samples. These results point to a key role for mitochondrial Complex I in the adequate functioning of ALDH-2. In addition, we have identified mitochondrial Complex I as one of the targets at which the initial oxidative stress responsible for GTN tolerance takes place. Our data also suggest a role for mitochondrial- antioxidants as therapeutic tools in the control of the tolerance that accompanies chronic nitrate use. © 2012 Elsevier B.V. © 2012 Elsevier B.V. All rights reserved.


Menchon C.,Institute dAlta Tecnologia PRBB | Martin R.,Polytechnic University of Valencia | Apostolova N.,University of Valencia | Victor V.M.,University of Valencia | And 4 more authors.
Small | Year: 2012

Ceria-supported gold nanoparticles are prepared exhibiting peroxidase activity and acting as radical traps. Au/CeO2 shows a remarkable biocompatibility as demonstrated by measuring cellular viability, proliferation, and lack of apoptosis for two human cell lines (Hep3B and HeLa). The antioxidant activity of Au/CeO2 against reactive oxygen species (ROS) is demonstrated by studying the cellular behavior of Hep3B and HeLa in a model of cellular oxidative stress. It is determined that Au/CeO2 exhibits higher antioxidant activity than glutathione, the main cytosolic antioxidant compound, and its CeO2 carrier. Overall the result presented here shows the potential of implementing well-established nanoparticulated gold catalysts with remarkable biocompatibility in cellular biology. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.


Davey C.G.,University of Melbourne | Allen N.B.,University of Melbourne | Harrison B.J.,University of Melbourne | Harrison B.J.,Institute dAlta Tecnologia PRBB | And 2 more authors.
Human Brain Mapping | Year: 2010

The experience of being liked is a key social event and fundamental to motivating human behavior, though little is known about its neural underpinnings. In this study, we examined the experience of being liked in a group of 15- to 24-year-old: a cohort for whom forming friendships has a great degree of salience, and for whom the explicit representation of relationships is familiar from their frequent use of social networking technologies. Study participants (n = 19) were led to believe that other participants had formed an opinion on their likability based on their appearance in a photograph, and during fMRI scanning viewed the photographs of people who had purportedly responded favorably to them (alongside photographs of control participants). Results indicated that being liked activated primary reward- and self-related regions, including the nucleus accumbens, midbrain (in an area corresponding to the ventral tegmentum), ventromedial prefrontal cortex, posterior cingulate cortex (including retrosplenial cortex), amygdala, and insula/opercular cortex. Participants showed greater activation of ventromedial prefrontal cortex and amygdala in response to being liked by people that they regarded highly compared to those they regarded less so. Finally, being liked by the opposite compared to the same gender activated the right caudal orbitofrontal cortex and right anterior insula: areas important for the representation of primary somatic rewards. This study demonstrates that neural response to being liked has features that are consistent with response to other rewarding events, but it has additional features that reflect its intrinsically interpersonal character. © 2009 Wiley-Liss, Inc.


Cocchi L.,University of Melbourne | Harrison B.J.,University of Melbourne | Harrison B.J.,Institute dAlta Tecnologia PRBB | Pujol J.,Institute dAlta Tecnologia PRBB | And 4 more authors.
Human Brain Mapping | Year: 2012

Objectives: Neuroimaging studies have consistently implicated alterations of the basal ganglia and orbitofrontal cortex in the pathophysiology of OCD, however, recent work also emphasizes more diffuse patterns of brain alteration as occurring in this disorder. The goal of this study was to extend such observations by investigating large-scale brain functional network correlates of cognitive-control performance in OCD patients. Experimental design: We combined fMRI with a validated task of cognitive control and a multivariate statistical method to assess multiple functional networks encompassing broad task-relevant cortical regions in OCD patients and matched controls. Functional networks of interest were targeted a priori and the groups were compared in terms of the spatiotemporal profile of network responses (functional connectivity) during the task performance in a data-driven manner. Principal observations: Task performance was equivalent in both groups and each distinct network demonstrated strong overlap in its general response during task. However, significant differences in functional connectivity were also observed between groups that appeared driven by specific phases of task performance. Such differences were most pronounced during rest-task transitions and mainly involved dorsal anterior cingulate and insular cortices within the paralimbic network. Relative heightened functional connectivity of insula in patients during task correlated with a measure of patients' state anxiety. Conclusions: Our findings provide a novel functional imaging characterization of brain network alterations associated with cognitive-control in OCD. Additionally, these findings raise questions about the role of patients' arousal states on the performance of cognitive imaging tasks that are otherwise assumed to be emotionally neutral. © 2011 Wiley-Liss, Inc.


PubMed | Institute dAlta Tecnologia PRBB
Type: Journal Article | Journal: Human brain mapping | Year: 2011

Obsessive-compulsive disorder (OCD) emerges during childhood through young adulthood coinciding with the late phases of postnatal brain development when fine remodeling of brain anatomy takes place. Previous research has suggested the existence of subtle anatomical alterations in OCD involving focal volume variations in different brain regions including the frontal lobes and basal ganglia. We investigated whether anatomical changes might also involve variations in the shape of the frontobasal region. A total of 101 OCD patients and 101 control subjects were examined using magnetic resonance imaging. A cross-sectional image highly representative of frontal-basal ganglia anatomy was selected in each individual and 25 reliable anatomical landmarks were identified to assess shape changes. A pixel-wise morphing approach was also used to dynamically illustrate the findings. We found significant group differences for overall landmark position and for most individual landmarks delimiting the defined frontobasal region. OCD patients showed a deformation pattern involving shortening of the anterior-posterior dimension of the frontal lobes and basal ganglia, and enlargement of cerebrospinal fluid spaces around the frontal opercula. In addition, we observed significant correlation of brain tissue shape variation with frontal sinus size. Identification of a global change in the shape of the frontobasal region may further contribute to characterizing the nature of brain alterations in OCD. The coincidence of brain shape variations with morphological changes in the frontal sinus indicates a potential association of OCD to late development disturbances, as the frontal sinus macroscopically emerges during the transition between childhood and adulthood.

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