Heme oxygenase-1 as a modulator of intestinal inflammation development and progression

Indexación: Scopus.Heme Oxygenase 1 (HMOX1) is an enzyme that catalyzes the reaction that degrades the heme group contained in several important proteins, such as hemoglobin, myoglobin, and cytochrome p450. The enzymatic reaction catalyzed by HMOX1 generates Fe2+, biliverdin and CO. It has been shown that HMOX1 activity and the by-product CO can downmodulate the damaging immune response in several models of intestinal inflammation as a result of pharmacological induction of HMOX1 expression and the administration of non-toxic amounts of CO. Inflammatory Bowel Diseases, which includes Crohn's Disease (CD) and Ulcerative Colitis (UC), are one of the most studied ailments associated to HMOX1 effects. However, microbiota imbalances and infections are also important factors influencing the occurrence of acute and chronic intestinal inflammation, where HMOX1 activity may play a major role. As part of this article we discuss the immune modulatory capacity of HMOX1 during IBD, as well during the infections and interactions with the microbiota that contribute to this inflammatory disease. © 2018 Sebastián, Salazar, Coronado-Arrázola, Schultz, Vallejos, Berkowitz, álvarez-Lobos, Riedel, Kalergis and Bueno.https://www.frontiersin.org/articles/10.3389/fimmu.2018.01956/ful

The Covid-19 explosion in the state of Amapá: how is the most preserved region in the Brazilian Amazon currently fighting the SARS-COV 2 pandemic?

The state of Amap\ue1 is located in the extreme north of Brazil, within the Amazon rainforest and is crossed by the Equator. It has a hot and humid climate with rains that last 8 months a year and 4 months of unrelenting sun that melts rubber from car seals, fries eggs on the floor and even cooks a whole egg tub, in case you forget in a car exposed to the sun . It was believed that with this potent solar incidence, the Sars-COV 2 virus would not have so much impact in this region, a terrible mistake! Today Amap\ue1 has the highest incidence of Covid-19 in the whole of Brazil, with a maid of 600 cases per hundred thousand inhabitants and in the Amazon it is the 3rd in deaths and loses in this item only to the state of Amazonas and Par\ue1

AKT1 and MYC induce distinctive metabolic fingerprints in human prostate cancer

Cancer cells may overcome growth factor dependence by deregulating oncogenic and/or tumor-suppressor pathways that affect their metabolism, or by activating metabolic pathways de novo with targeted mutations in critical metabolic enzymes. It is unknown whether human prostate tumors develop a similar metabolic response to different oncogenic drivers or a particular oncogenic event results in its own metabolic reprogramming. Akt and Myc are arguably the most prevalent driving oncogenes in prostate cancer. Mass spectrometry-based metabolite profiling was performed on immortalized human prostate epithelial cells transformed by AKT1 or MYC, transgenic mice driven by the same oncogenes under the control of a prostate-specific promoter, and human prostate specimens characterized for the expression and activation of these oncoproteins. Integrative analysis of these metabolomic datasets revealed that AKT1 activation was associated with accumulation of aerobic glycolysis metabolites, whereas MYC overexpression was associated with dysregulated lipid metabolism. Selected metabolites that differentially accumulated in the MYC-high versus AKT1-high tumors, or in normal versus tumor prostate tissue by untargeted metabolomics, were validated using absolute quantitation assays. Importantly, the AKT1/MYC status was independent of Gleason grade and pathologic staging. Our fi ndings show how prostate tumors undergo a metabolic reprogramming that refl ects their molecular phenotypes, with implications for the development of metabolic diagnostics and targeted therapeutics.Instituto de Investigaciones Bioquímicas de La PlataFacultad de Ciencias Médica

Determinants of image quality of rotational angiography for on-line assessment of frame geometry after transcatheter aortic valve implantation

To study the determinants of image quality of rotational angiography using dedicated research prototype software for motion compensation without rapid ventricular pacing after the implantation of four commercially available catheter-based valves. Prospective observational study including 179 consecutive patients who underwent transcatheter aortic valve implantation (TAVI) with either the Medtronic CoreValve (MCS), Edward-SAPIEN Valve (ESV), Boston Sadra Lotus (BSL) or Saint-Jude Portico Valve (SJP) in whom rotational angiography (R-angio) with motion compensation 3D image reconstruction was performed. Image quality was evaluated from grade 1 (excellent image quality) to grade 5 (strongly degraded). Distinction was made between good (grades 1, 2) and poor image quality (grades 3–5). Clinical (gender, body mass index, Agatston score, heart rate and rhythm, artifacts), procedural (valve type) and technical variables (isocentricity) were related with the image quality assessment. Image quality was good in 128 (72 %) and poor in 51 (28 %) patients. By univariable analysis only valve type (BSL) and the presence of an artefact negatively affected image quality. By multivariate analysis (in which BMI was forced into the model) BSL valve (Odds 3.5, 95 % CI [1.3–9.6], p = 0.02), presence of an artifact (Odds 2.5, 95 % CI [1.2–5.4], p = 0.02) and BMI (Odds 1.1, 95 % CI [1.0–1.2], p = 0.04) were independent predictors of poor image quality. Rotational angiography with motion compensation 3D image reconstruction using a dedicated research prototype software offers good image quality for the evaluation of frame geometry after TAVI in the majority of patients. Valve type, presence of artifacts and higher BMI negatively affect image quality

A Novel Method for High-Dimensional Anatomical Mapping of Extra-Axial Cerebrospinal Fluid: Application to the Infant Brain

Cerebrospinal fluid (CSF) plays an essential role in early postnatal brain development. Extra-axial CSF (EA-CSF) volume, which is characterized by CSF in the subarachnoid space surrounding the brain, is a promising marker in the early detection of young children at risk for neurodevelopmental disorders. Previous studies have focused on global EA-CSF volume across the entire dorsal extent of the brain, and not regionally-specific EA-CSF measurements, because no tools were previously available for extracting local EA-CSF measures suitable for localized cortical surface analysis. In this paper, we propose a novel framework for the localized, cortical surface-based analysis of EA-CSF. The proposed processing framework combines probabilistic brain tissue segmentation, cortical surface reconstruction, and streamline-based local EA-CSF quantification. The quantitative analysis of local EA-CSF was applied to a dataset of typically developing infants with longitudinal MRI scans from 6 to 24 months of age. There was a high degree of consistency in the spatial patterns of local EA-CSF across age using the proposed methods. Statistical analysis of local EA-CSF revealed several novel findings: several regions of the cerebral cortex showed reductions in EA-CSF from 6 to 24 months of age, and specific regions showed higher local EA-CSF in males compared to females. These age-, sex-, and anatomically-specific patterns of local EA-CSF would not have been observed if only a global EA-CSF measure were utilized. The proposed methods are integrated into a freely available, open-source, cross-platform, user-friendly software tool, allowing neuroimaging labs to quantify local extra-axial CSF in their neuroimaging studies to investigate its role in typical and atypical brain development

Changes in the Frontotemporal Cortex and Cognitive Correlates in First-Episode Psychosis

Background: Loss of cortical volume in frontotemporal regions has been reported in patients with schizophrenia and their relatives. Cortical area and thickness are determined by different genetic processes, and measuring these parameters separately may clarify disturbances in corticogenesis relevant to schizophrenia. Our study also explored clinical and cognitive correlates of these parameters.Methods: Thirty-seven patients with first-episode psychosis (34 schizophrenia, 3 schizoaffective disorder) and 38 healthy control subjects matched for age and sex took part in the study. Imaging was performed on an magnetic resonance imaging 1.5-T scanner. Area and thickness of the frontotemporal cortex were measured using a surface-based morphometry method (Freesurfer). All subjects underwent neuropsychologic testing that included measures of premorbid and current IQ, working and verbal memory, and executive function.Results: Reductions in cortical area, more marked in the temporal cortex, were present in patients. Overall frontotemporal cortical thickness did not differ between groups, although regional thinning of the right superior temporal region was observed in patients. There was a significant association of both premorbid IQ and IQ at disease onset with area, but not thickness, of the frontotemporal cortex, and working memory span was associated with area of the frontal cortex. These associations remained significant when only patients with schizophrenia were considered.Conclusions: Our results suggest an early disruption of corticogenesis in schizophrenia, although the effect of subsequent environmental factors cannot be excluded. In addition, cortical abnormalities are subject to regional variations and differ from those present in neurodegenerative diseases

Sex differences associated with corpus callosum development in human infants: A longitudinal multimodal imaging study

The corpus callosum (CC) is the largest connective pathway in the human brain, linking cerebral hemispheres. There is longstanding debate in the scientific literature whether sex differences are evident in this structure, with many studies indicating the structure is larger in females. However, there are few data pertaining to this issue in infancy, during which time the most rapid developmental changes to the CC occur. In this study, we examined longitudinal brain imaging data collected from 104 infants at ages 6, 12, and 24 months. We identified sex differences in brain-size adjusted CC area and thickness characterized by a steeper rate of growth in males versus females from ages 6–24 months. In contrast to studies of older children and adults, CC size was larger for male compared to female infants. Based on diffusion tensor imaging data, we found that CC thickness is significantly associated with underlying microstructural organization. However, we observed no sex differences in the association between microstructure and thickness, suggesting that the role of factors such as axon density and/or myelination in determining CC size is generally equivalent between sexes. Finally, we found that CC length was negatively associated with nonverbal ability among females

Subcortical Brain and Behavior Phenotypes Differentiate Infants With Autism Versus Language Delay

Background Younger siblings of children with autism spectrum disorder (ASD) are themselves at increased risk for ASD and other developmental concerns. It is unclear if infants who display developmental concerns, but are unaffected by ASD, share similar or dissimilar behavioral and brain phenotypes to infants with ASD. Most individuals with ASD exhibit heterogeneous difficulties with language, and their receptive-expressive language profiles are often atypical. Yet, little is known about the neurobiology that contributes to these language difficulties. Methods In this study, we used behavioral assessments and structural magnetic resonance imaging to investigate early brain structures and associations with later language skills. High-risk infants who were later diagnosed with ASD (n = 86) were compared with high-risk infants who showed signs of early language delay (n = 41) as well as with high- and low-risk infants who did not have ASD or language delay (n = 255 and 143, respectively). Results Results indicated that diminished language skills were evident at 12 months in infants with ASD and infants with early language delay. At 24 months of age, only the infants with ASD displayed atypical receptive-expressive language profiles. Associations between 12-month subcortical volumes and 24-month language skills were moderated by group status, indicating disordinal brain-behavior associations among infants with ASD and infants with language delay. Conclusions These results suggest that there are different brain mechanisms influencing language development in infants with ASD and infants with language delay, and that the two groups likely experience unique sets of genetic and environmental risk factors