Estilo comportamental al inicio del segundo año de vida:estudio retrospectivo en escolares afectados de trastorno por deficit de atencion e hiperactividad

OBJECTIVES: To study the relationship between behavioural profile of children suffering from Attention Deficit Hyperactivity Disorder (ADHD) and the previous behavioural style of these patients as toddlers. SUBJECTS AND METHODS: We asked the parents of 50 schoolchildren with ADHD, and those of 30 controls, to fill in a Spanish version of the Toddler Behaviour Questionnaire (TBQ) from their retrospective perception of their children's behaviour as toddlers. TBQ items were grouped by factor analysis; t-Student between the scores of both groups and a multiple correlation analysis of TBQ and DSM-IV-ADHD-RS in each of the groups were used. RESULTS: Children in the ADHD group were reported by parents to have had a different toddler behavioural profile in comparison to that of control children (P<0.05). These differences were associated with adapting to new environments, mood, regularity and stability of play behaviour. A correlation was found between behavioural profile in DSM-IV-ADHD- RS and TBQ. CONCLUSIONS: The results of this study should be interpreted with caution. However, they suggest that in the fifth trimester of life a particular behavioural style as regards regularity, stability of play, and mood, could indicate a risk of developing ADHD in the future. This behavioural style should be taken into consideration in rearing and early education prospective studies

Transplantation of mesenchymal stem cells exerts a greater long-term effect than bone marrow mononuclear cells in a chronic myocardial infarction model in rat

The aim of this study is to assess the long-term effect of mesenchymal stem cells (MSC) transplantation in a rat model of chronic myocardial infarction (MI) in comparison with the effect of bone marrow mononuclear cells (BM-MNC) transplant. Five weeks after induction of MI, rats were allocated to receive intramyocardial injection of 106 GFP-expressing cells (BM-MNC or MSC) or medium as control. Heart function (echocardiography and 18F-FDG-microPET) and histological studies were performed 3 months after transplantation and cell fate was analyzed along the experiment (1 and 2 weeks and 1 and 3 months). The main findings of this study were that both BM-derived populations, BM-MNC and MSC, induced a long-lasting (3 months) improvement in LVEF (BM-MNC: 26.61 ± 2.01% to 46.61 ± 3.7%, p < 0.05; MSC: 27.5 ± 1.28% to 38.8 ± 3.2%, p < 0.05) but remarkably, only MSC improved tissue metabolism quantified by 18FFDG uptake (71.15 ± 1.27 to 76.31 ± 1.11, p < 0.01), which was thereby associated with a smaller infarct size and scar collagen content and also with a higher revascularization degree. Altogether, results show that MSC provides a long-term superior benefit than whole BM-MNC transplantation in a rat model of chronic MI

18F-FDG metabolism in a rat model of chronic infarction: a 17-sector semiquantitative analysis

Strategies to establish the functional benefit of cell therapy in cardiac regeneration and the potential mechanism are needed. Aims: Development of a semi-quantitative method for non invasive assessment of cardiac viability and function in a rat model of myocardial infarction (MI) based on the use of microPET. Animals, methods: Ten rats were subjected to myocardial imaging 2, 7, 14, 30, 60 and 90 days after left coronary artery ligation. Intravenous 18F-fluoro-2-deoxy-2-D-glucose (18F-FDG) was administered and regional 18F activity concentrations per unit area were measured in 17 regions of interest (ROIs) drawn on cardiac polar maps. By comparing the differences in 18F uptake between baseline and each of the follow up time points, parametric polar maps of statistical significance (PPMSS) were calculated. Left ventricular ejection fraction (LVEF) was blindly assessed echocardiographically. All animals were sacrificed for histopathological analysis after 90 days. Results: The diagnostic quality of 18F-FDG microPET images was excellent. PPMSS demonstrated a statistically significant decrease in 18F concentrations as early as 48 hours after MI in 4 of the 17 ROIs (segments 7, 13, 16 and 17; p <0.05) that persisted throughout the study. Semi-quantitative analysis of 18F-FDG uptake correlated with echocardiographic decrease in LVEF (p <0.001). Conclusion: The use of PPMSS based on 18F-FDG-microPET provides valuable semi-quantitative information of heart glucose metabolism allowing for non-invasive follow up thus representing a useful strategy for assessment of novel therapies in cardiac regeneration

Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [18F]FDG and sodium [18F]fluoride PET

BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and young adults that produces aberrant osteoid. The aim of this study was to assess the utility of 2-deoxy-2-[18F-] fluoro-D-glucose ([18F] FDG) and sodium [18F] Fluoride (Na [18F] F) PET scans in orthotopic murine models of osteosarcoma to describe the metabolic pattern of the tumors, to detect and diagnose tumors and to evaluate the efficacy of a new treatment based in oncolytic adenoviruses. METHODS: Orthotopic osteosarcoma murine models were created by the injection of 143B and 531MII cell lines. [18F]FDG and Na [18F] F PET scans were performed 30 days (143B) and 90 days (531MII) post-injection. The antitumor effect of two doses (107 and 108 pfu) of the oncolytic adenovirus VCN-01 was evaluated in 531 MII model by [18F] FDG PET studies. [18F] FDG uptake was quantified by SUVmax and Total Lesion Glycolysis (TLG) indexes. For Na [18F] F, the ratio tumor SUVmax/hip SUVmax was calculated. PET findings were confirmed by histopathological techniques. RESULTS: The metabolic pattern of tumors was different between both orthotopic models. All tumors showed [18F] FDG uptake, with a sensitivity and specificity of 100%. The [18F] FDG uptake was significantly higher for the 143B model (p < 0.001). Sensitivity for Na [18F] F was around 70% in both models, with a specificity of 100%. 531MII tumors showed a heterogeneous Na [18F] F uptake, significantly higher than 143B tumors (p < 0.01)

Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [18F]FDG and sodium [18F]fluoride PET

BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and young adults that produces aberrant osteoid. The aim of this study was to assess the utility of 2-deoxy-2-[18F-] fluoro-D-glucose ([18F] FDG) and sodium [18F] Fluoride (Na [18F] F) PET scans in orthotopic murine models of osteosarcoma to describe the metabolic pattern of the tumors, to detect and diagnose tumors and to evaluate the efficacy of a new treatment based in oncolytic adenoviruses. METHODS: Orthotopic osteosarcoma murine models were created by the injection of 143B and 531MII cell lines. [18F]FDG and Na [18F] F PET scans were performed 30 days (143B) and 90 days (531MII) post-injection. The antitumor effect of two doses (107 and 108 pfu) of the oncolytic adenovirus VCN-01 was evaluated in 531 MII model by [18F] FDG PET studies. [18F] FDG uptake was quantified by SUVmax and Total Lesion Glycolysis (TLG) indexes. For Na [18F] F, the ratio tumor SUVmax/hip SUVmax was calculated. PET findings were confirmed by histopathological techniques. RESULTS: The metabolic pattern of tumors was different between both orthotopic models. All tumors showed [18F] FDG uptake, with a sensitivity and specificity of 100%. The [18F] FDG uptake was significantly higher for the 143B model (p < 0.001). Sensitivity for Na [18F] F was around 70% in both models, with a specificity of 100%. 531MII tumors showed a heterogeneous Na [18F] F uptake, significantly higher than 143B tumors (p < 0.01)

Monoaminergic PET imaging and histopathological correlation in unilateral and bilateral 6-hydroxydopamine lesioned rat models of Parkinson's disease: a longitudinal in-vivo study

Carbon-11 labeled dihydrotetrabenazine (11C-DTBZ) binds to the vesicular monoamine transporter 2 and has been used to assess nigro-striatal integrity in animal models and patients with Parkinson's disease. Here, we applied 11C-DTBZ positron emission tomography (PET) to obtain longitudinally in-vivo assessment of striatal dopaminergic loss in the classic unilateral and in a novel bilateral 6-hydroxydopamine (6-OHDA) lesion rat model. Forty-four Sprague–Dawley rats were divided into 3 sub-groups: 1. 6-OHDA-induced unilateral lesion in the medial forebrain bundle, 2. bilateral lesion by injection of 6-OHDA in the third ventricle, and 3. vehicle injection in either site. 11C-DTBZ PET studies were investigated in the same animals successively at baseline, 1, 3 and 6 weeks after lesion using an anatomically standardized volumes-of-interest approach. Additionally, 12 rats had PET and Magnetic Resonance Imaging to construct a new 11C-DTBZ PET template. Behavior was characterized by rotational, catalepsy and limb-use asymmetry tests and dopaminergic striatal denervation was validated post-mortem by immunostaining of the dopamine transporter (DAT). 11C-DTBZ PET showed a significant decrease of striatal binding (SB) values one week after the unilateral lesion. At this point, there was a 60% reduction in SB in the affected hemisphere compared with baseline values in 6-OHDA unilaterally lesioned animals. A 46% symmetric reduction over baseline SB values was found in bilaterally lesioned rats at the first week after lesion. SB values remained constant in unilaterally lesioned rats whereas animals with bilateral lesions showed a modest (22%) increase in binding values at the 3rd and 6th weeks post-lesion. The degree of striatal dopaminergic denervation was corroborated histologically by DAT immunostaining. Statistical analysis revealed a high correlation between 11C-DTBZ PET SB and striatal DAT immunostaining values (r = 0.95, p < 0.001). The data presented here indicate that 11C-DTBZ PET may be used to ascertain changes occurring in-vivo throughout the evolution of nigro-striatal dopaminergic neurodegeneration, mainly in the unilateral 6-OHDA lesion rat

MAPC transplantation confers a more durable benefit than AC133+ cell transplantation

There is a need for comparative studies to determine which cell types are better candidates to remedy ischemia. Here, we compared human AC133+ cells and Multipotent Adult Progenitor Cells (hMAPC) in a mouse model reminiscent of critical limb ischemia. hMAPC or hAC133+ cell transplantation induced a significant improvement in tissue perfusion (measured by microPET) 15 days post-transplantation compared to controls. This improvement persisted for 30 days in hMAPC-treated but not in hAC133+-injected animals. While transplantation of hAC133+ cells promoted capillary growth, hMAPC transplantation also induced collateral expansion, decreased muscle necrosis/fibrosis and improved muscle regeneration. Incorporation of differentiated hAC133+ or hMAPC progeny into new vessels was limited, however, a paracrine angio/arteriogenic effect was demonstrated in animals treated with hMAPC. Accordingly, hMAPC-, but not hAC133+-conditioned media, stimulated vascular cell proliferation and prevented myoblast, endothelial and smooth muscle cell apoptosis in vitro. Our study suggests that although hAC133+ cell and hMAPC transplantation bothcontribute to vascular regeneration in ischemic limbs, hMAPC exert a more robust effect through trophic mechanisms, which translated into collateral and muscle fiber regeneration. This, in turn, conferred tissue protection and regeneration with longer-term functional improvement

Infection-specific PET imaging with 18F-fluorodeoxysorbitol and 2-[18F]F-ρ-aminobenzoic acid: An extended diagnostic tool for bacterial and fungal diseases

IntroductionSuspected infectious diseases located in difficult-to-access sites can be challenging due to the need for invasive procedures to isolate the etiological agent. Positron emission tomography (PET) is a non-invasive imaging technology that can help locate the infection site. The most widely used radiotracer for PET imaging (2-deoxy-2[18F] fluoro-D-glucose: [18F]FDG) shows uptake in both infected and sterile inflammation. Therefore, there is a need to develop new radiotracers able to specifically detect microorganisms.MethodsWe tested two specific radiotracers: 2-deoxy-2-[18F]-fluoro-D-sorbitol ([18F]FDS) and 2-[18F]F-ρ-aminobenzoic acid ([18F]FPABA), and also developed a simplified alternative of the latter for automated synthesis. Clinical and reference isolates of bacterial and yeast species (19 different strains in all) were tested in vitro and in an experimental mouse model of myositis infection.Results and discussionNon-lactose fermenters (Pseudomonas aeruginosa and Stenotrophomonas maltophilia) were unable to take up [18F]FDG in vitro. [18F]FDS PET was able to visualize Enterobacterales myositis infection (i.e., Escherichia coli) and to differentiate between yeasts with differential assimilation of sorbitol (i.e., Candida albicans vs. Candida glabrata). All bacteria and yeasts tested were detected in vitro by [18F]FPABA. Furthermore, [18F]FPABA was able to distinguish between inflammation and infection in the myositis mouse model (E. coli and Staphylococcus aureus) and could be used as a probe for a wide variety of bacterial and fungal species

Estilo comportamental al inicio del segundo año de vida:estudio retrospectivo en escolares afectados de trastorno por deficit de atencion e hiperactividad

OBJECTIVES: To study the relationship between behavioural profile of children suffering from Attention Deficit Hyperactivity Disorder (ADHD) and the previous behavioural style of these patients as toddlers. SUBJECTS AND METHODS: We asked the parents of 50 schoolchildren with ADHD, and those of 30 controls, to fill in a Spanish version of the Toddler Behaviour Questionnaire (TBQ) from their retrospective perception of their children's behaviour as toddlers. TBQ items were grouped by factor analysis; t-Student between the scores of both groups and a multiple correlation analysis of TBQ and DSM-IV-ADHD-RS in each of the groups were used. RESULTS: Children in the ADHD group were reported by parents to have had a different toddler behavioural profile in comparison to that of control children (P<0.05). These differences were associated with adapting to new environments, mood, regularity and stability of play behaviour. A correlation was found between behavioural profile in DSM-IV-ADHD- RS and TBQ. CONCLUSIONS: The results of this study should be interpreted with caution. However, they suggest that in the fifth trimester of life a particular behavioural style as regards regularity, stability of play, and mood, could indicate a risk of developing ADHD in the future. This behavioural style should be taken into consideration in rearing and early education prospective studies

Assesment of treatments against Staphylococcus aureus biofilms using in vivo 18F-FDG-PET in an animal model

Trabajo presentado en la 26th European Association of Nuclear Medicine (EANM) annual congress, celebrada en Lyon (Francia) en 2013.Biofilms are aggregates of microorganisms that may be formed on different surfaces as medical implants. Their appearance is associated to almost undetectable and persistent infections that hardly respond to antibiotic treatments. Consequently, the development of new antibiotic therapies and of adequate techniques to confirm their effectiveness is of utmost importance.[Aim] to evaluate the feasibility of 18F-FDG-PET imaging for in vivo monitoring of bacterial biofilm infections and quantifying the response to antibiotic treatments in an animal model.[Methodology] sealed catheters of VialonTM biomaterial were pre-colonized with Staphylococcus aureus ATCC15981 and subcutaneously implanted in CD1 mice (n=14). Half of these animals (n=7) received oral rifampicin (0.5 mg/day) for 7 days. The infection was monitored in vivo by 18F-FDG-PET imaging at days 1, 7 and 14 after catheter implantation. For this, an 18F-FDG-PET (18,3±1,6 MBq) was injected in the tail vein, and after 60 minutes under continuous isoflurane anesthesia, a static PET image was performed. 18F-FDG uptake was quantified by means of SUV, drawing volumes of interest over the catheters and lymph nodes. In parallel, an additional group of untreated mice (n=9) was used to determine both the number of colony forming units (CFU) per catheter and the histopathological changes (i.e. presence of inflammatory cells and bacteria) in the surrounding area of the catheter.[Results] 18F-FDG-PET produced a quantifiable signal already at 1 day post-implant. The signal was found associated with the appearance of bacteria and polymorphonuclear cells in the area of the catheter. Moreover, a high 18F-FDG-PET uptake in lymph nodes was observed in the non-treated group at days 7 and 14. At day 7, the rifampicin-treated group showed a statistically significant reduction in both SUV values (p=0.006) and number of viable CFU (p<0.001) in catheters, and lymph node images became negative. At day 14 (one week after treatment was stopped), the SUV values of catheter and lymph nodes increased in the treated group, reaching levels similar to those of the control group, compatible with the growth of surviving bacteria.[Conclusions] 18F-FDG-PET could be an innovative and useful technique to detect in vivo biofilm infections, in follow-up studies and evaluation of the efficacy of antibiotic therapies in living mice.Peer Reviewe