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Congenital cervicofacial vascular anomalies are extremely rare and present many difficulties in diagnosis and treatment requiring a multidisciplinary approach. Firstly, there is little consensus on this subject among head and neck specialists. There are two main types of vascular anomalies: vascular tumors and vascular malformations. Vascular malformations are also divided into malformations with slow blood flow (veins, lymphatics, capillaries or combined) and malformations with a fast blood flow (arteriovenous malformations and fistula). Vascular tumors like hemangiomas are known for their spontaneous involution with aging, while vascular malformations grow in dimensions with age. It is very important to choose the correct differential diagnosis between cervicofacial hemangiomas and vascular malformations for proper therapy management. Anamnesis and clinical exams help in raising suspicions about the real nature of a cervico-vascular anomaly. Furthermore, imaging brings in-depth details of the anomaly, ranging from ultrasound and contrast CT to MRI scanning and minimally invasive angiography. Angiography with selective embolization is rarely a curative procedure for arteriovenous malformations, being more suitable as a preliminary step before attempted surgical removal. Surgery is clearly necessary when there are aesthetic and functional deficits. Slow-flow vascular malformations present a reduced morbidity, and in cases without involution, the surgical ablation is reserved for the cases with aesthetic dysfunctions or psychological trauma. Lymphatic malformations must undergo surgical ablation when they are associated with mass effects and compression of great vessels or aerial viscera. The prognosis after surgical removal is good, with a low rate of recurrence or morbidity. Fast-flow vascular malformations require a combined approach, with embolization and excision in the next 48 h for safety reasons. Removal may be followed by reconstructive surgery depending on the location and dimensions of the malformation, with a possible secondary recovery of the normal microscopic vessels. Some of the masses may hinder the normal airflow and swallowing. Pathology is the gold standard for confirming the clinical and imaging diagnosis.
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NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are instrumental in all inflammatory phases of atherosclerosis. Dysregulated histone deacetylase (HDAC)-related epigenetic pathways have been mechanistically linked to alterations in gene expression in experimental models of cardiovascular disorders. Hitherto, the relation between HDAC and Nox in atherosclerosis is not known. We aimed at uncovering whether HDAC plays a role in mediating Nox up-regulation, oxidative stress, inflammation, and atherosclerotic lesion progression. Human non-atherosclerotic and atherosclerotic arterial samples, ApoE-/- mice, and in vitro polarized monocyte-derived M1/M2-macrophages (Mac) were examined. Male ApoE-/- mice, maintained on normal or high-fat, cholesterol-rich diet, were randomized to receive 10â¯mg/kg suberoylanilide hydroxamic acid (SAHA), a pan-HDAC inhibitor, or its vehicle, for 4 weeks. In the human/animal studies, real-time PCR, Western blot, lipid staining, lucigenin-enhanced chemiluminescence assay, and enzyme-linked immunosorbent assay were employed. The protein levels of class I, class IIa, class IIb, and class IV HDAC isoenzymes were significantly elevated both in human atherosclerotic tissue samples and in atherosclerotic aorta of ApoE-/- mice. Treatment of ApoE-/- mice with SAHA reduced significantly the extent of atherosclerotic lesions, and the aortic expression of Nox subtypes, NADPH-stimulated ROS production, oxidative stress and pro-inflammatory markers. Significantly up-regulated HDAC and Nox subtypes were detected in inflammatory M1-Mac. In these cells, SAHA reduced the Nox1/2/4 transcript levels. Collectively, HDAC inhibition reduced atherosclerotic lesion progression in ApoE-/- mice, possibly by intertwined mechanisms involving negative regulation of Nox expression and inflammation. The data propose that HDAC-oriented pharmacological interventions could represent an effective therapeutic strategy in atherosclerosis.
Assuntos
Apolipoproteínas E/deficiência , Aterosclerose/etiologia , Aterosclerose/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , NADPH Oxidases/genética , Estresse Oxidativo/efeitos dos fármacos , Animais , Aorta/metabolismo , Aorta/patologia , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Biópsia , LDL-Colesterol/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Epigênese Genética , Humanos , Masculino , Camundongos , Camundongos Knockout , NADPH Oxidases/metabolismo , Oxirredução , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Histone acetylation plays a major role in epigenetic regulation of gene expression. Monocyte-derived macrophages express functional NADPH oxidase 5 (Nox5) that contributes to oxidative stress in atherogenesis. The mechanisms of Nox5 regulation are not entirely elucidated. The aim of this study was to investigate the expression pattern of key histone acetyltransferase subtypes (p300, HAT1) in human atherosclerosis and to determine their role in mediating the upregulation of Nox5 in macrophages under inflammatory conditions. Human nonatherosclerotic and atherosclerotic tissue samples were collected in order to determine the expression of p300 and HAT1 isoforms, H3K27ac, and Nox5. In vitro determinations were done on human macrophages exposed to lipopolysaccharide in the absence or presence of histone acetyltransferase inhibitors. Western blot, immunohistochemistry, immunofluorescence, real-time PCR, transfection, and chromatin immunoprecipitation assay were employed. The protein levels of p300 and HAT1 isoforms, H3K27ac, and Nox5 were found significantly elevated in human atherosclerotic specimens. Immunohistochemistry/immunofluorescence staining revealed that p300, HAT1, H3K27ac, H3K9ac, and Nox5 proteins were colocalized in the area of CD45+/CD68+ immune cells and lipid-rich deposits within human atherosclerotic plaques. Lipopolysaccharide induced the levels of HAT1, H3K27ac, H3K9ac, and Nox5 and the recruitment of p300 and HAT1 at the sites of active transcription within Nox5 gene promoter in cultured human macrophages. Pharmacological inhibition of histone acetyltransferase significantly reduced the Nox5 gene and protein expression in lipopolysaccharide-challenged macrophages. The overexpression of p300 or HAT1 enhanced the Nox5 gene promoter activity. The histone acetyltransferase system is altered in human atherosclerosis. Under inflammatory conditions, HAT subtypes control Nox5 overexpression in cultured human macrophages. The data suggest the existence of a new epigenetic mechanism underlying oxidative stress in atherosclerosis.
Assuntos
Aterosclerose/metabolismo , Proteína p300 Associada a E1A/metabolismo , Histona Acetiltransferases/metabolismo , Macrófagos/enzimologia , NADPH Oxidase 5/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Aterosclerose/enzimologia , Aterosclerose/genética , Aterosclerose/patologia , Proteína p300 Associada a E1A/genética , Epigênese Genética , Histona Acetiltransferases/genética , Histonas/biossíntese , Histonas/genética , Histonas/metabolismo , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , NADPH Oxidase 5/biossíntese , NADPH Oxidase 5/genética , Células THP-1 , Transfecção , Regulação para CimaRESUMO
The fibrous skeleton is concentrated at the base of the ventricular mass. It provides electrical insulation at the atrioventricular level and fibrous continuity for the leaflets of the mitral, aortic, and tricuspid valves. Its components include the fibrous trigones, the fibrous area of aortic-mitral continuity, the subvalvar collar of the mitral valve, the membranous septum, the interleaflet triangles, the tendon of Todaro, and likely the conus ligament. The majority of the mitral annulus is fibrous, but the only true fibrous part of the tricuspid annulus is where the valvar leaflets are attached to the central fibrous body. At the aortic annulus, the fibrous elements support only the noncoronary aortic sinus and parts of the right and left coronary sinuses. The ring-shaped annulus of the arterioventricular valves as localized with imaging techniques (imaging annulus) differs from the crown-shaped hemodynamic annulus of the arterial valves. The imaging annulus corresponds to the plane passing through the nadirs of the hinge-lines of the leaflets. The hinges of the pulmonary valve are not part of the fibrous skeleton. Computed tomography (CT) and magnetic resonance (MR) imaging are excellent modalities for evaluation of the anatomy, physiologic variations, and pathologic conditions of the fibrous skeleton. The submillimeter isotropic three-dimensional datasets obtained with CT and the high contrast resolution of MR imaging are the main advantages of these modalities in assessing anatomy. The function of the valves and associated annuli can best be studied with MR imaging. Pathologic conditions involving the area, including paravalvar leaks, abscesses, perforation, and pseudoaneurysms, usually occur as a complication of infective endocarditis or extensive calcifications after valvar surgery. MR imaging and CT can demonstrate these lesions equally well. CT is the preferred technique for showing the extent of calcifications in the fibrous skeleton. Large calcifications involving the central fibrous body can cause heart block by interfering with the normal function of the His bundle and its branches. ©RSNA, 2017.
Assuntos
Cardiopatias/diagnóstico por imagem , Cardiopatias/patologia , Coração/anatomia & histologia , Coração/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Calcinose/diagnóstico por imagem , Coração/embriologia , HumanosRESUMO
Because the systemic and pulmonary circulations are arranged in series, the right and left ventricles of the human heart have similar stroke volumes (with only minute beat-to-beat changes). Besides propelling the same volume of blood through the corresponding circulations, the two ventricles also share common structures such as the pericardium, the interventricular septum and the coronary arteries and veins-all of which complete the dynamic and integrated picture of the human heart. However, there are marked differences between the left and right ventricles as each is adapted to separate and dissimilar vascular beds, including particular reactivity to stress, hormones, and drugs. Of the two, the right ventricle (RV) has so far been either more difficult to approach from the diagnostic point of view or even overlooked, while the left ventricle (LV) has been considered the main pump, and diagnostic and therapeutic measures have been considered to apply equally to the LV and RV. This review article presents an update, portraying the RV from the clinical anatomical point of view, and endeavors to underscore the main particulars of the RV with clinical and surgical applications.
Assuntos
Ventrículos do Coração/anatomia & histologia , Desenvolvimento Embrionário , Cardiopatias/patologia , Humanos , Infarto do Miocárdio/etiologiaRESUMO
Two main causes of arterial thrombosis are known: fi rst - atherosclerosis, extensively studied, and the second - atrial fi brillation. The lack of any risk factors and the occurrence at young age of a thrombotic event requires us to investigate possible other conditions, including inherited thrombophilia that is represented by a series of genetic disorders that increase the risk of thromboembolic disease. The role of thrombophilia in the occurrence of arterial thrombosis is inconsequential; this disorder is characterized by the tendency of developing venous thrombosis. We present a rare case of a 29 year old woman that presents an arterial thrombotic event subsequent to the caesarean section. The patient had a positive familial history for thrombotic events and a cavernous sinus thrombosis in personal history. Prophylactic treatment with unfractionated heparin throughout pregnancy was applied. At 31 weeks gestation the patient underwent cesarean surgery for nonreassuring fetal status, 2 weeks fetal intrauterine growth restriction and absent diastolic fl ow of uterine arteries. Three days post operatory arterial thrombosis is suspected. The context that led to this suspicion was paresthesia, color modifi cation of the right leg and abolished popliteal pulse. Angiographic-CT confi rmed the presumptive diagnosis. A cardiovascular, conservatory treatment was successfully applied. Considering the particularities of the presented case we discuss the occurrence of arterial thrombosis postpartum in the context of confi rmed thrombophilia by reviewing the specialized literature.
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Monocytes (Mon) and Mon-derived macrophages (Mac) orchestrate important oxidative and inflammatory reactions in atherosclerosis by secreting reactive oxygen species (ROS) due, in large part, to the upregulated NADPH oxidases (Nox). The Nox enzymes have been extensively investigated in human Mon and Mac. However, the expression and functional significance of the Nox5 subtypes is not known. We aimed at elucidating whether Nox5 is expressed in human Mon and Mac, and examine its potential role in atherosclerosis. Human monocytic THP-1 cell line and CD14(+) Mon were employed to search for Nox5 expression. RT-PCR, Western blot, lucigenin-enhanced chemiluminescence and dihydroethidium assays were utilized to examine Nox5 in these cells. We found that Nox5 transcription variants and proteins are constitutively expressed in THP-1 cells and primary CD14(+) Mon. Silencing of Nox5 protein expression by siRNA reduced the Ca(2+)-dependent Nox activity and the formation of ROS in Mac induced by A23187, a selective Ca(2+) ionophore. Exposure of Mac to increasing concentrations of IFNγ (5-100 ng/ml) or oxidized LDL (5-100 µg/ml) resulted in a dose-dependent increase in Nox5 protein expression and elevation in intracellular Ca(2+) concentration. Immunohistochemical staining revealed that Nox5 is present in CD68(+) Mac-rich area within human carotid artery atherosclerotic plaques. To the best of our knowledge, this is the first evidence that Nox5 is constitutively expressed in human Mon. Induction of Nox5 expression in IFNγ- and oxidized LDL-exposed Mac and the presence of Nox5 in Mac-rich atheroma are indicative of the implication of Nox5 in atherogenesis.
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Aterosclerose/enzimologia , Macrófagos/metabolismo , Proteínas de Membrana/metabolismo , Monócitos/enzimologia , NADPH Oxidases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular , Humanos , NADPH Oxidase 5RESUMO
BACKGROUND: The precise knowledge of regional anatomical details is of utmost importance specially in complex procedures such as the Ross operation. This anatomical study offers a critical approach regarding the advantages, limits, and precautions for this procedure. METHODS: Using dissection techniques, magnifications up to x6 and nontraditional approaches, 68 fixed normal heart specimens were studied over a 2-year period. The details of surgical relevance such as the boundaries and relations of the pulmonary and aortic roots, their vascularization, and the number and distribution of the septal arteries are described. RESULTS: The aortic and pulmonary roots include interdependent elements functioning in a coordinated manner and establishing important relations with adjacent structures. Both coronary arteries vascularize the arterial roots. The infundibular branches from the right coronary artery are larger and more constant. The septal arteries establish important relations with the pulmonary infundibulum but their contribution to its vascularization is negligible. In this series, the main septal artery was the second, showing the longest retroinfundibular course. However, no constant relation was found between this vessel and the intraventricular landmarks. CONCLUSIONS: A novel approach was used by performing nontraditional dissections of the arterial roots and by studying their vascularization The depicted details are useful to the surgeon specializing in the Ross procedure and represent the basis for further research.