[18F]-FMISO PET/MRI Imaging Shows Ischemic Tissue around Hematoma in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH), being the most severe cerebrovascular disease, accounts for 10-15% of all strokes. Hematoma expansion is one of the most important factors associated with poor outcome in intracerebral hemorrhage (ICH). Several studies have suggested that an "ischemic penumbra" might arise when the hematoma has a large expansion, but clinical studies are inconclusive. We performed a preclinical study to demonstrate the presence of hypoxic-ischemic tissue around the hematoma by means of longitudinal [18F]-fluoromisonidazole ([18F]-FMISO) PET/MRI studies over time in an experimental ICH model. Our results showed that all [18F]-FMISO PET/MRI images exhibited hypoxic-ischemic tissue around the hematoma area. A significant increase of [18F]-FMISO uptake was found at 18-24 h post-ICH when the maximum of hematoma volume is achieved and this increase disappeared before 42 h. These results demonstrate the presence of hypoxic tissue around the hematoma and open the possibility of new therapies aimed to reduce ischemic damage associated with ICH.

MUC1 deficiency mediates corticosteroid resistance in chronic obstructive pulmonary disease.

BACKGROUND: Lung inflammation in COPD is poorly controlled by inhaled corticosteroids (ICS). Strategies to improve ICS efficacy or the search of biomarkers who may select those patients candidates to receive ICS in COPD are needed. Recent data indicate that MUC1 cytoplasmic tail (CT) membrane mucin can mediate corticosteroid efficacy in chronic rhinosinusitis. The objective of this work was to analyze the previously unexplored role of MUC1 on corticosteroid efficacy in COPD in vitro and in vivo models. METHODS: MUC1-CT expression was measured by real time PCR, western blot, immunohistochemistry and immunofluorescence. The inflammatory mediators IL-8, MMP9, GM-CSF and MIP3α were measured by ELISA. The effect of MUC1 on inflammation and corticosteroid anti-inflammatory effects was measured using cell siRNA in vitro and Muc1-KO in vivo animal models. RESULTS: MUC1-CT expression was downregulated in lung tissue, bronchial epithelial cells and lung neutrophils from smokers (n = 11) and COPD (n = 11) patients compared with healthy subjects (n = 10). MUC1 was correlated with FEV1% (ρ = 0.7479; p < 0.0001) in smokers and COPD patients. Cigarette smoke extract (CSE) decreased the expression of MUC1 and induced corticosteroid resistance in human primary bronchial epithelial cells and human neutrophils. MUC1 Gene silencing using siRNA-MUC1 impaired the anti-inflammatory effects of dexamethasone and reduced glucocorticoid response element activation. Dexamethasone promoted glucocorticoid receptor alpha (GRα) and MUC1-CT nuclear translocation and co-localization that was inhibited by CSE. Lung function decline and inflammation induced by lipopolysaccharide and cigarette smoke in Muc1 KO mice was resistant to dexamethasone. CONCLUSIONS: These results confirm a role for MUC1-CT mediating corticosteroid efficacy in COPD.

Coronary vascular disease event risk and metabolic syndrome prevalence in patients enrolled in an assertive treatment community program.

OBJECTIVE: To examine the risk of coronary vascular disease event (CVDE) and the prevalence metabolic syndrome (MS) and its cardiovascular risk factors (CVRF) in patients with severe mental illnesses enrolled in an assertive treatment community program (ATC) in Spain. METHOD: We carried out a cross-sectional descriptive study with all of the patients included in an ATC program in 2016 in a health area with 547,328 inhabitants in Galicia, Spain. We identified the CVRF in all the individuals, and calculated MS and 10-year CVDE. We also compared the prevalence of all traits in our cohort and the general population. RESULTS: The 10-year median of coronary vascular disease event (CVDE10) was 8.4%. The percentage of individuals with high CVDE10 (>5%) was 41.2% The CVDE10 median was higher in men than women (10.5% vs 5.1%, p<0.001). MS was detected in 50% of patients without differences between men and women (51.2% vs 48.2%). A prevalence of 68% was found for smoking, 55% for dyslipidemia, 47% for obesity, 29% for impaired glucose metabolism, and 38% for hypertension. Women showed a higher prevalence of obesity measured by elevated waist circumference (88.9% vs 55.6%, p=0.003). Men showed a higher prevalence of arterial hypertension (46.6% vs 22.2%, p=0.0001). CONCLUSIONS: The SMD Patients enrolled in ATC programs had a 1.5-times higher prevalence of MS and 8 times higher CVDE10 than those reported in the general population. Individual CVRF were also higher in the SMD patients. Prevention, early detection, and comprehensive treatment are important issues for patients with severe mental illnesses.

Relación entre la pureza radioquímica del 123i-ioflupano y la captación extracraneal (tiroidea y parotídea) / Relationship between radiochemical purity of 123i-ioflupane and extracranial image captation (parotid and thyroid

Objetivo. Estudiar el efecto de la pureza radioquímica (PR) del 123I-Ioflupano, utilizado para realizar SPECT cerebral de transportadores de dopamina, sobre las imágenes obtenidas y evaluar la posible influencia de la extravasación durante su administración y del grado de afectación del paciente por el síndrome parkinsoniano sobre los resultados. Material y métodos. Se realizó un estudio prospectivo en 39 pacientes. La PR del 123I-Ioflupano se determinó mediante cromatografía en capa fina. Se delimitaron las regiones de interés (ROI) en zona aproximada de cerebro, parótidas y región cervical, obteniéndose la media de cuentas en cada región y las ratios de actividad tiroides/cerebro (RTC) y parótidas/cerebro (RPC). Se propuso un modelo de regresión lineal múltiple con predictores cuantitativos y categóricos. Resultados. El modelo mostró correlación entre la PR y la RTC modificada por la presencia de extravasación, fue estadísticamente significativo (p<0,001 y predijo el 42,31% de la variabilidad de la RTC. La correlación entre PR y RPC no se modificó por ninguna de las variables propuestas. El modelo fue estadísticamente significativo (p<0,0176) y predijo el 12,3% de la variabilidad del RPC. Conclusiones. La capacidad predictiva del modelo para explicar la variabilidad de la RTC es aceptable y explica la repercusión negativa de la extravasación. Sin embargo, la capacidad para explicar la variabilidad de la RPC es baja y debe ser atribuida a variables no estudiadas. Una PR baja y la extravasación durante la administración del radiofármaco se traduce en mayor actividad extracraneal e implica peor calidad de imagen y mayor irradiación tiroidea

Aim. The aim of this study is to see the effect of radiochemical purity (PR) of 123I- Ioflupane used for cerebral dopamine transporter SPECT (Single Photon Emission Computed Tomography) on the images and evaluate the possible influence of extravasation during the administration in patient with Parkinson syndrome. Material and methods. A Prospective study was performed in 39 patients. The PR of 123I-Ioflupane was determined by radiochromatography. The regions of interest (ROI) were defined in general area of the brain, parotid and cervical region, obtaining the average counts in each region and activity ratios thyroid / brain (RTC) and parotid / brain (RPC). It was proposed a model of multiple linear regression with quantitative and categorical predictors Results. The model showed that correlation between the PR and the RTC was modified by the presence of extravasation, it was statistically significant (p < 0.001) and predicted the 42.31 % of the variability of the RTC. The correlation between PR and PRC was not modified by any of the variables proposed. The model was statistically significant (p < 0.0176) and 12.3% predicted variability RPC Conclusions. The predictive variability of the model of RTC is acceptable and explains the negative impact of extravasation. However, the ability to explain the variability of the PRC is low and should not be attributed to variables studied. A low PR and extravasation during the administration of the radiopharmaceutical involves worse quality of image and increased thyroid irradiation