Comparing cardiac CT angiography and MR angiography in evaluating left ventricular function and volumes / Comparación de la angiografía por TC y la angiografía por RM para evaluar la función y los volúmenes del ventrículo izquierdo

Abstract Background: cardiovascular diseases are among the principal causes of mortality and morbidity worldwide. Prevention, early diagnosis and treatment can play an important role in reducing complication of cardiovascular diseases. Objectives: Considering increasing popularity of cardiac computed tomography CT angiography (CTA) in one side and also magnetic esonance angiography (MRA) as gold standard modality on the other side, we decided to perform this meta-analysis study to compare cardiac CTA and MRA in evaluating left ventricular volumes. Method: this study is a systematic review in which we included all studies with inclusion criteria and without exclusion criteria up to 30 December, 2019. Studies were selected after searching on different databases and articles in bibliography of included studies. Obtained studies were screened for quality. Required data were extracted and were then analyzed via STATA 11 statistical package. Results: among 90 articles obtained in primary search, finally 19 studies entered data extraction and synthesis. Based on our meta-analysis, standardized mean difference was -0.09 (95% CI -0.2, 0.02) for end systolic volume (ESV), -0.10 (95% CI -0.22, 0.01) for end diastolic volume (EDV), 0.10 (95% CI -0.01, 0.22) for ejection fraction (EF) and -0.09 (95% CI -0.23, 0.04) for stroke volume (SV). Conclusion: Results of this systematic review and meta-analysis showed that there is no statistically significant difference between CTA and MRA in evaluating ESV, EDV, EF and SV. Based on our findings, it can be interpreted that CTA has similar accuracy with MRA in evaluating ventricular volumes.

Resumen Introducción: Las enfermedades cardiovasculares están entre las principales causas de morbimortalidad global. La prevención, el diagnóstico precoz y el tratamiento pueden desempeñar un papel importante en la reducción de las complicaciones de las enfermedades cardiovasculares. Objetivo: Teniendo en cuenta la creciente popularidad de la angiografía por tomografía computarizada (ATC) cardiaca, por un lado, y también la angiografía por resonancia magnética (ARM) como el método de referencia, por el otro, decidimos llevar a cabo un metaanálisis para comparar la ATC y la ARM cardiaca en la evaluación de los volúmenes del ventrículo izquierdo. Método: Revisión sistemática en la cual incluimos todos los estudios con criterios de inclusión y sin criterios de exclusión hasta el 30 de diciembre de 2019. Los estudios se seleccionaron de diferentes bases de datos y artículos de las bibliografías de los estudios incluidos. Los estudios obtenidos se examinaron para evaluar su calidad. Los datos requeridos fueron extraídos y luego analizados utilizando el paquete estadístico STATA 11. Resultados: De los 90 artículos obtenidos en la búsqueda primaria, finalmente 19 estudios entraron a extracción de datos y síntesis. Según nuestro metaanálisis, la diferencia de medias estandarizada fue de −0.09 (intervalo de confianza del 95% [IC95%] −0.2 a 0.02) para el volumen sistólico final (VSF), −0.10 (IC95%: −0.22 a 0.01) para el volumen diastólico final (VDF), 0.10 (IC95%: −0.01 a 0.22) para la fracción de eyección (FE) y − 0.09 (IC95%: −0.23 a 0.04) para el volumen sistólico (VS). Conclusiones: Los resultados de esta revisión sistemática y metaanálisis mostraron que no existe una diferencia estadísticamente significativa entre la ATC y la ARM en la evaluación del VSF, el VDF, la FE y el VS. Basado en nuestros hallazgos, se puede interpretar que la ATC tiene una precisión parecida a la ARM en la evaluación de los volúmenes ventriculares.

Redirected charge transport arising from diazonium grafting of carbon coated LiFePO4.

The morphological and the electrical properties of carbon coated LiFePO4 (LFPC) active material functionalized by 4-ethynylbenzene tetrafluoroboratediazonium salt were investigated. For this purpose, FTIR, Raman, XPS, High Resolution Transmission Electron Microscopy (HRTEM) and Broadband Dielectric Spectroscopy (BDS) were considered. Electronic conductivities of LFPC samples at room temperature were found to decrease in a large frequency range upon simple immersion in polar solvents and to decrease further upon functionalization. Due to their high dipole moment, strongly physisorbed molecules detected by XPS likely add barriers to electron hopping. Significant alteration of the carbon coating conductivity was only observed, however, upon functionalization. This effect is most presumably associated with an increase in the sp(3) content determined by Raman spectroscopy, which is a strong indication of the formation of a covalent bond between the organic layer and the carbon coating. In this case, the electron flux appears to be redirected and relayed by short-range (intra chain) and long-range (inter chain) electron transport through molecular oligomers anchored at the LFPC surface. The latter are controlled by tunnelling and slightly activated hopping, which enable higher conductivity at low temperature (T < 250 K). Alteration of the electron transport within the carbon coating also allows detection of a relaxation phenomenon that corresponds to small polaron hopping in bulk LiFePO4. XPS and HRTEM images allow a clear correlation of these findings with the island type oligomeric structure of grafted molecules.

Multiscale electronic transport in Li(1+x)Ni(1/3-u)Co(1/3-v)Mn(1/3-w)O2: a broadband dielectric study from 40 Hz to 10 GHz.

This work is the first detailed study concerning the multiscale electronic transport and its temperature dependence in the LiNi1/3Co1/3Mn1/3O2 (NMC) family, high-capacity electrode materials for lithium ion batteries. Powders with two different mean cluster sizes (3 µm and 10 µm) but the same particle sizes (0.4 to 1.3 µm) were measured. The detailed formula of the studied compound is Li1.04Ni(2+)0.235Ni(3+)0.09Mn(4+)0.315Co(3+)0.32O2. Different electrical relaxations are evidenced, resulting from the polarizations at the different scales of the powder architecture. When the frequency increases, three dielectric relaxations are detected in the following order due to: (a) space-charge polarization (low-frequency range) owing to the interface between the sample and the conductive metallic layer deposited on it; (b) polarization of NMC clusters (micronic scale) induced by the existence of resistive junctions between them; and (c) polarization of NMC particles (at sub-micronic scale) induced by resistive junctions between them. High interatomic level conductivity of about 20 S m(-1) was evidenced and attributed to the contribution of the extended states and to a Brownian motion of the charge carriers with mean free path similar to the lattice constant. The ratio between sample and local conductivity is more than 10(5). The large conductivity drop of 3 to 4 orders of magnitude is observed from the particle to the cluster scale. A very large number of charge carriers are blocked by the interparticle junctions within the clusters. The conductivity drop from the cluster to the sample scale is comparatively very small, owing to the dense architecture of the NMC sample in which the spherical clusters are very piled up on each other.

Traumatic brain injury induces prolonged accumulation of cyclooxygenase-1 expressing microglia/brain macrophages in rats.

Inflammatory cellular responses to brain injury are promoted by proinflammatory messengers. Cyclooxygenases (prostaglandin endoperoxide H synthases [PGH]) are key enzymes in the conversion of arachidonic acid into prostanoids, which mediate immunomodulation, mitogenesis, apoptosis, blood flow, secondary injury (lipid peroxygenation), and inflammation. Here, we report COX-1 expression following brain injury. In control brains, COX-1 expression was localized rarely to brain microglia/macrophages. One to 5 days after injury, we observed a highly significant (p < 0.0001) increase in COX-1+ microglia/macrophages at perilesional areas and in the developing core with a delayed culmination of cell accumulation at day 7, correlating with phagocytic activity. There, cell numbers remained persistently elevated up to 21 days following injury. Further, COX-1+ cells were located in perivascular Virchow-Robin spaces also reaching maximal numbers at day 7. Lesion-confined COX-1+ vessels increased in numbers from day 1, reaching the maximum at days 5-7. Double-labeling experiments confirmed coexpression of COX-1 by ED-1+ and OX-42+ microglia/ macrophages. Transiently after injury, most COX-1+ microglia/macrophages coexpress the activation antigen OX-6 (MHC class II). However, the prolonged accumulation of COX-1+, ED-1+ microglia/macrophages in lesional areas enduring the acute postinjury inflammatory response points to a role of COX-1 in the pathophysiology of secondary injury. We have identified localized, accumulated COX-1 expression as a potential pharmacological target in the treatment of brain injury. Our results suggest that therapeutic approaches based on long-term blocking including COX-1, might be superior to selective COX-2 blocking to suppress the local synthesis of prostanoids.

Localization of endostatin in rat and human gliomas.

BACKGROUND: Endostatin is a potent inhibitor of endothelial cell proliferation, angiogenesis, and tumor growth. Its occurrence and localization has not yet been examined in human brain tumors. The authors report the production of a monoclonal antibody and detection of endostatin in rat and human gliomas by immunohistochemistry. METHODS: The authors analyzed localization and tissue distribution of endostatin in 41 paraffin embedded glioma samples (18 glioblastoma multiforme, 7 WHO Grade III astrocytomas, 13 fibrillary, and 3 protoplasmic WHO Grade II astrocytomas) of human origin and 21 rat C6 gliomas by immunohistochemistry. Double labeling experiments confirmed the origin of endostatin-labeled cells. RESULTS: Endostatin immunoreactivity was detected in tumor cells, endothelial cells, macrophages, and lymphocytes of both rat and human gliomas. The percentage of cells labeled with the endostatin antibody was significantly lower (P = 0.0126) in the tumor parenchyma of human glioblastomas than in WHO Grade II astrocytomas. CONCLUSIONS: Endostatin was present in various cell types in rat and human gliomas in vivo. Lower levels in glioblastomas than in WHO Grade II astrocytomas might have reflected the shift of a probable regulatory balance between promoters and inhibitors of angiogenesis towards facilitation of neovascularization.

IL-16 is differentially expressed in the developing human fetal brain by microglial cells in zones of neuropoesis.

Microglial cells are regulators of tissue homeostasis in the adult central nervous system and readily participate in pathological processes, orchestrating tissue remodeling. Cytokines produced by microglial cells are markers of cell activation and contribute to reactive processes. In this paper, we have studied the expression of IL-16 (leukocyte chemoattractant factor), a natural soluble ligand to the CD4 molecule, in human fetal brains from the 11th to the 20th(.) week of gestation by immunohistochemistry. Interleukin (IL)-16(+) cells were detected already at the 11th gestational week, accumulating with aging in cortical layers (P<0.0001) at the 16th and 19th week, and reaching maximum numbers in the 20th week. Most IL-16(+) microglia (>80%) revealed morphological hallmarks of activated microglia. We observed that IL-16 cells coexpress LCA (>80%) and MRP-8, an activation-associated Ca(2+) binding S-100 family member (>80%). In contrast, only few IL-16(+) cells proliferated (PCNA(+), 20-40%) or co-expressed the HLA-DR, -DP, or -DQ antigen (<10%), and rare coexpression with CD68 (20-40%) was detected until 17th week. No coexpression with CD4, CD8 or CD20 was detected. Furthermore, we observed accumulation of IL-16(+) microglia in zones of neuronal proliferation, migration and differentiation. Increasing numbers of IL-16(+) cells were detected in bordering zones adjacent to the basal ganglia. Our data suggests that the early presence of IL-16(+) microglia exert a CD4-independent function-mediating activation, and chemotaxis of microglia precursors during neuronal development. In addition, IL-16 immunoreactivity might be a helpful tool to determine distinct developmental stages of microglial cells during fetal central nervous system ontogeny.

Transient in vivo activation of rat brain macrophages/microglial cells and astrocytes by immunostimulatory multiple CpG oligonucleotides.

Certain DNA sequences containing motifs of unmethylated CpG nucleotides are immunostimulatory and might contribute to the development of inflammatory lesions after infections. CpG motifs might further contribute to side effects of oligonucleotide-based therapeutic approaches. Here we have analyzed the effects of intracranial injections of synthetic CpG oligonucleotides. We observed that oligonucleotides with several unmethylated CpG motifs, but not methylated or inverted GpC motifs, stimulated microglial cells and astrocytes of the rat brain. This transient, self-limiting response is maximal at day 3 after injection and subsides until day 5. Activated microglial cells could be identified to produce two novel monocytic peptides, the allograft inflammatory factor-1 (AIF-1) and endothelial monocyte activating polypeptide II (EMAP II). Astrocytes were similarly activated as shown by expression of the enzyme heme-oxygenase-1 (HO-1). Glial cell proliferation (expression of PCNA) or aptosis was not observed. Thus immunostimulatory DNA activates the local innate immune defense system of the brain, and might contribute transiently to infectious, inflammatory and degenerative responses of the central nervous system.

Allograft inflammatory factor-1 defines a distinct subset of infiltrating macrophages/microglial cells in rat and human gliomas.

Allograft inflammatory factor-1 (AIF-1) is a Ca2+-binding peptide that constitutes a potential modulator of macrophage activation and function during the immune response of the brain. Peptides termed microglia response factor-1 or ionized calcium-binding adaptor molecule- have been reported to be identical with AIF-1. We have investigated the expression of AIF-1 in the rat C6 glioblastoma and 9L gliosarcoma tumor models and additionally assessed AIF- expression in a diverse range of human astrocytomas by immunohistochemistry. AIF-1 was expressed by activated microglial cells and a subset of infiltrating macrophages in areas of infiltrative tumor growth and in compact tumor areas in both rat and human gliomas. Double-labeling experiments in rats and humans characterized the nature and the functional status of AIF-1+ cells. AIF-1 expression was detected in cells expressing major histocompatibility complex class II molecules and in a subset of activated macrophages/microglial cells. All MRP-8+ cells coexpressed AIF-1. In humans, there was a strong correlation of AIF-1-expressing activated macrophages/microglial cells with tumor malignancy (P < 0.0001). These results suggest that AIF-1 defines a distinct subset of tumor-associated activated macrophages/ microglial cells.

Heme oxygenase-1 in lesions of rat experimental autoimmune encephalomyelitis and neuritis.

The enzyme heme oxygenase-1 (HO-1) is reducing heme to the gaseous mediator carbon monoxide, to iron and the antioxidant biliverdin. The inducible expression of HO-1 is considered a protective cellular mechanism against reactive oxygen intermediates. Further, carbon monoxide (CO) is a regulator of cGMP synthesis, of NO-synthetases and cyclooxygenases, thereby indirectly modulating reactive processes. Here we report expression of HO-1 in rat experimental autoimmune encephalomyelitis (EAE) and neuritis (EAN). With both models, similar results were obtained: HO-1 was localized predominantly to infiltrating, monocytic, but only rarely to ramified microglial cells or astrocytes surrounding the inflammatory lesions. Prominent expression by monocytic cells was seen from day 11 after immunization correlating with the development of neurologic disease. Further, local expression is persistent for long after cessation of neurologic signs. Thus, HO-1 could be considered a factor in the formation and resolution of inflammatory autoimmune lesions of the nervous system.

Dynamics of microglial activation after human traumatic brain injury are revealed by delayed expression of macrophage-related proteins MRP8 and MRP14.

Human traumatic brain injury (TBI) is ideally suited for investigation of the kinetics of human microglial cell activation as the onset of lesion formation is precisely defined. The present study provides evidence of a distinct delay in macrophage/microglia response following TBI. Eighteen brains of patients who had survived TBI for 1 h to 6 months were analysed by immunohistology. Samples of contusional and non-contusional areas were studied using antibodies directed against antigens of microglia/ macrophages [major histocompatibility complex class II, CD4, interleukin (IL)-16, macrophage-related protein (MRP) 8 and MRP14]. IL-16, a natural ligand to CD4, was expressed constitutively by numerous microglial cells in all cases throughout the brain. CD4 could be detected regularly on perivascular cells. MRP8 and MRP14, which are only expressed on activated macrophages and microglial cells, could be detected only within brains with a survival time of more than 72 h post TBI. In addition, proliferation of microglia detected by MIB-1 was not present until 72 h. This delayed expression of the activation markers MRP8 and MRP14 and the proliferation marker MIB-1 is comparable to experimental closed head injuries but strictly different from acute activation found in ischemic brains.

Effects of autoantigen and dexamethasone treatment on expression of endothelial-monocyte activating polypeptide II and allograft-inflammatory factor-1 by activated macrophages and microglial cells in lesions of experimental autoimmune encephalomyelitis, neuritis and uveitis.

Endothelial-monocyte activating polypeptide II (EMAP II) and allograft-inflammatory factor-1 (AIF-1) are two proteins produced by activated monocytes and microglial cells. We now report expression of these factors during experimental therapy of rat neuroautoimmune diseases. Comparative analysis of two therapeutic strategies, treatment with high doses of recombinant autoantigens or with dexamethasone, revealed unexpected differences. High doses of autoantigen were most effective in experimental autoimmune encephalomyelitis and neuritis (EAE and EAN), but less effective in experimental autoimmune uveitis (EAU). Low and high doses of dexamethasone treatment greatly reduced the severity of EAE, EAN and EAU at day 11, but a relapse was observed between days 21 and 26. Only rather limited expression of EMAP II and AIF-1 is seen in the normal central nervous system (CNS). This constitutive expression is not abolished by dexamethasone treatment. In inflammatory autoimmune lesions of the rat CNS, prominent AIF-1 and EMAP II staining was seen with macrophages and monocytes. In particular, parenchymal microglial cells were now activated to express AIF-1 and EMAP II. In accordance with prevention of neurological signs, histological observations revealed that accumulation of activated monocytes expressing EMAP II and AIF-1 in the CNS or peripheral nervous system and the massive expression of these factors by parenchymal microglial cells is inhibited by high doses of autoantigen. Dexamethasone prevented or abolished local expression of EMAP II and AIF-1 at days 10-16. However, an acute and severe relapse occurred in encephalomyelitis between days 20-26. In these cases, a smoldering expression of EMAP II and AIF-1 persisting long after cessation of neurological signs was observed. Thus, expression of EMAP II and AIF-1 by infiltrating activated macrophages is a marker of disease activity and expression of these factors could be used to demonstrate 'silent' lesions in the CNS and prolonged microglial cell activation. Apparently, AIF-1 and EMAP II immunoreactivity are tools to stage activation of monocytes and microglial cells in inflammatory lesions.

Allograft-inflammatory factor-1 in rat experimental autoimmune encephalomyelitis, neuritis, and uveitis: expression by activated macrophages and microglial cells.

Allograft inflammatory factor-1 (AIF-1) is a Ca2+ binding peptide expressed predominantly by activated monocytes. In order to investigate the role of AIF-1 in autoimmune lesions of the rat nervous system, we have used a synthetic gene to express AIF-1 in E. coli and have produced monoclonal antibodies against AIF-1. AIF-1 was localized to monocytes/macrophages with rather selective staining of a minor rat monocyte subpopulation of lymphoid tissue. We then investigated expression of AIF-1 in experimental autoimmune encephalomyelitis (EAE), neuritis (EAN), and uveitis (EAU). Within the local inflammatory lesions, infiltrating macrophages are prominently stained. In the diseased brain, AIF-1-positive microglial cells are not only found in the direct vicinity of the infiltrate, but widespread activation is seen in the parenchyma. This is the first demonstration that AIF-1 is present in autoimmune lesions. Immunostaining of microglial cells is noteworthy, as these cells are strategically placed regulatory elements of CNS immunosurveillance. Thus, AIF-1 might be a valuable marker to dissect the local monocyte heterogeneity in autoimmune disease.

Localization of endothelial-monocyte-activating polypeptide II (EMAP II), a novel proinflammatory cytokine, to lesions of experimental autoimmune encephalomyelitis, neuritis and uveitis: expression by monocytes and activated microglial cells.

Endothelial-Monocyte-Activating Polypeptide II (EMAP II) is a proinflammatory cytokine and chemoattractant of macrophages. In order to investigate the role of EMAP II in autoimmune lesions of the rat nervous system, we have used a synthetic gene to express EMAP II in E. coli and have produced monoclonal antibodies against EMAP II. Monoclonal antibodies are suited to demonstrate EMAP II in ELISAs, Western blots, and paraffin-embedded tissue sections. EMAP II was localized to monocytes/macrophages with rather selective staining of a minor rat monocyte subpopulation of lymphoid tissues such as spleen, lymph nodes or follicles of the gut. In the normal brain, cells of the perivascular but not parenchymal microglia were stained. We then investigated expression of EMAP II during experimental autoimmune encephalomyelitis (EAE), neuritis (EAN), and uveitis (EAU). Within the local inflammatory lesions infiltrating macrophages are prominently stained. In the diseased brain, EMAP II-positive microglial cells are not only found in the direct vicinity of the inflammatory infiltrate, but widespread activation is seen in the parenchyma. This is the first demonstration that EMAP II is present in autoimmune lesions. Immunostaining of microglial cells is noteworthy, as these cells are strategically placed regulatory elements of CNS immunosurveillance. EMAP II might be a factor regulating monocyte chemoattraction, endothelial cell activation and a regulator of microglial cell reactivity in autoimmune inflammation of the central nervous system.

Leukocyte chemotactic factor, a natural ligand to CD4, is expressed by lymphocytes and microglial cells of the MS plaque.

The leukocyte chemotactic factor (LCF) is a proinflammatory cytokine and natural soluble ligand to the human CD4 molecule. LCF is produced by CD4+ and CD8+ T lymphocytes and is considered essential to the influx of CD4+ T lymphocytes and macrophages into an inflammatory lesion. In order to investigate the role of LCF in the multiple sclerosis (MS) lesion, we have used a synthetic gene to express LCF in E. coli and have produced monoclonal antibodies against LCF. Monoclonal antibodies are suited to demonstrate LCF in ELISAs. Western blots and paraffin-embedded tissue sections. In the MS lesion, immunopositive lymphocytes and microglial cells, notably, have been found. This is the first demonstration that LCF is present in MS lesions. Immunostaining of microglial cells is noteworthy, as these cells are strategically placed regulatory elements of CNS immunosurveillance and like other cells of the monocytic lineage express CD4 molecules. Thus, LCF might be a paracrine factor regulating T-lymphocyte chemoattraction and an autocrine molecule regulating microglial cell immune reactivity.