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BACKGROUND: The distinct arterial and venous cell fates are dictated by a combination of various genetic factors which form diverse types of blood vessels such as arteries, veins, and capillaries. We report here that YULINK protein is involved in vasculogenesis, especially venous formation. METHODS: In this manuscript, we employed gene knockdown, yeast two-hybrid, FLIM-FRET, immunoprecipitation, and various imaging technologies to investigate the role of YULINK gene in zebrafish and human umbilical vein endothelial cells (HUVECs). RESULTS: Knockdown of YULINK during the arterial-venous developmental stage of zebrafish embryos led to the defective venous formation and abnormal vascular plexus formation. Knockdown of YULINK in HUVECs impaired their ability to undergo cell migration and differentiation into a capillary-like tube formation. In addition, the phosphorylated EPHB4 was decreased in YULINK knockdown HUVECs. Yeast two-hybrid, FLIM-FRET, immunoprecipitation, as well as imaging technologies showed that YULINK colocalized with endosome related proteins (EPS15, RAB33B or TICAM2) and markers (Clathrin and RHOB). VEGF-induced VEGFR2 internalization was also compromised in YULINK knockdown HUVECs, demonstrating to the involvement of YULINK. CONCLUSION: This study suggests that YULINK regulates vasculogenesis, possibly through endocytosis in zebrafish and HUVECs.
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Saccharomyces cerevisiae , Peixe-Zebra , Animais , Humanos , Células Endoteliais da Veia Umbilical Humana , Peixe-Zebra/genética , Movimento Celular , Diferenciação Celular , Neovascularização FisiológicaRESUMO
SUMMARY: Neuropeptide calcitonin gene-related peptide (CGRP) is a neurotransmitter related to vasculogenesis during organ development. The vascular endothelial growth factor A (VEGF-A) is also required for vascular patterning during lung morphogenesis. CGRP is primarily found in organs and initially appears in pulmonary neuroendocrine cells during the early embryonic stage of lung development. However, the relationship between CGRP and VEGF-A during lung formation remains unclear. This study investigates CGRP and VEGF-A mRNA expressions in the embryonic, pseudoglandular, canalicular, saccular, and alveolar stages of lung development from embryonic day 12.5 (E12.5) to postnatal day 5 (P5) through quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization. Further, we analyzed the expression of CGRP via immunohistochemistry. The VEGF-A mRNA was mainly scattered across the whole lung body from E12.5. CGRP was found to be expressed in a few epithelial cells of the canalicular and the respiratory bronchiole of the lung from E12.5 to P5. An antisense probe for CGRP mRNA was strongly detected in the lung from E14.5 to E17.5. Endogenous CGRP may regulate the development of the embryonic alveoli from E14.5 to E17.5 in a temporal manner.
El péptido relacionado con el gen de la calcitonina (CGRP) es un neurotransmisor vinculado con la vasculogénesis durante el desarrollo de órganos. El factor de crecimiento endotelial vascular A (VEGF-A) también se requiere para el patrón vascular durante la morfogénesis pulmonar. El CGRP se encuentra principalmente en los órganos y aparece inicialmente en las células neuroendocrinas pulmonares durante la etapa embrionaria temprana del desarrollo pulmonar. Sin embargo, la relación entre CGRP y VEGF-A durante la formación de los pulmones sigue sin estar clara. Este estudio investiga las expresiones de ARNm de CGRP y VEGF-A en las etapas embrionaria, pseudoglandular, canalicular, sacular y alveolar del desarrollo pulmonar desde el día embrionario 12,5 (E12,5) hasta el día postnatal 5 (P5) a través de la reacción en cadena de la polimerasa cuantitativa en tiempo real. (qRT-PCR) e hibridación in situ. Además, analizamos la expresión de CGRP mediante inmunohistoquímica. El ARNm de VEGF-A se dispersó principalmente por todo parénquima pulmonar desde E12,5. Se encontró que CGRP se expresaba en unas pocas células epiteliales de los bronquiolos canaliculares y respiratorios del pulmón desde E12,5 a P5. Se detectó fuertemente una sonda antisentido para ARNm de CGRP en el pulmón de E14,5 a E17,5. El CGRP endógeno puede regular el desarrollo de los alvéolos embrionarios de E14,5 a E17,5 de manera temporal.
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Animais , Camundongos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Pulmão/crescimento & desenvolvimento , Pulmão/embriologia , Imuno-Histoquímica , Hibridização In Situ , Neurotransmissores , Neovascularização FisiológicaRESUMO
BACKGROUND: The distinct arterial and venous cell fates are dictated by a combination of various genetic factors which form diverse types of blood vessels such as arteries, veins, and capillaries. We report here that YULINK protein is involved in vasculogenesis, especially venous formation. METHODS: In this manuscript, we employed gene knockdown, yeast two-hybrid, FLIM-FRET, immunoprecipitation, and various imaging technologies to investigate the role of YULINK gene in zebrafish and human umbilical vein endothelial cells (HUVECs). RESULTS: Knockdown of YULINK during the arterial-venous developmental stage of zebrafish embryos led to the defective venous formation and abnormal vascular plexus formation. Knockdown of YULINK in HUVECs impaired their ability to undergo cell migration and differentiation into a capillary-like tube formation. In addition, the phosphorylated EPHB4 was decreased in YULINK knockdown HUVECs. Yeast two-hybrid, FLIM-FRET, immunoprecipitation, as well as imaging technologies showed that YULINK colocalized with endosome related proteins (EPS15, RAB33B or TICAM2) and markers (Clathrin and RHOB). VEGF-induced VEGFR2 internalization was also compromised in YULINK knockdown HUVECs, demonstrating to the involvement of YULINK. CONCLUSION: This study suggests that YULINK regulates vasculogenesis, possibly through endocytosis in zebrafish and HUVECs. Key points Knockdown of YULINK with morpholino in embryos of double transgenic zebrafish exhibited abnormal venous formation. Tube formation and phosphorylated EPHB4 were decreased in YULINK knockdown HUVECs. FLIM-FRET, immunoprecipitation, as well as other imaging technologies showed that YULINK colocalized with endosome related proteins (EPS15, RAB33B and TICAM2) and endosome markers (Clathrin and RHOB). Knockdown of YULINK decreased the internalization of VEGF and VEGFR2 in HUVECs.
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Humanos , Animais , Saccharomyces cerevisiae , Peixe-Zebra/genética , Diferenciação Celular , Movimento Celular , Neovascularização Fisiológica , Células Endoteliais da Veia Umbilical HumanaRESUMO
Microvascular channel growth and inhibition, such as what occurs in vasculogenic mimicry, are generally represented in tables or shown in bar graphs. Although informative, those representations lack accurate predictions on dosage or the opportunity to report an unbiased metric when one wants to compare different signal dependence, for instance, the concentration of different drugs or enzymes or expression levels of particular genes.Mathematical model building is an exercise that makes you think of which are the key variables of a particular phenomenon and how they affect the targeting experimental output.Starting from early blood vessel formation and regression (number of vessels) due to an inducer/inhibitor effect, we show how a conceptual mathematical model may be built. As an example, the model was used to parameterize aloin bioactivity on a chick yolk sac membrane (YSM) assay with respect to its vasculogenic and vessel regression properties. A separable functional form where vessel formation and cell death occur as mutually exclusive concentration or signal-dependent functions showed that there was a good correlation with experimental data. Although an analytical solution for that simple case is presented, parameter determination and parametric analysis may be carried out numerically by solving the system of ordinary differential equations that represents the model using nonlinear regression for parameter determinations. Such model formulation thus allows for a more objective evaluation concentration dependence and is suggested as a novel method to evaluate blood vessel formation and inhibition as well as a general model for quantitative balance between chemical stimulation and toxicity.
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Modelos Teóricos , Saco Vitelino , MatemáticaRESUMO
The aim of this work was to evaluate the expression profile of genes involved in signaling, intracellular and extracellular Ca+2 concentration and apoptosis pathways of osteoblasts in contact with a scaffold made of a composite of BCN/MWCNTs. Osteoblasts were cultivated on BCN, MWCNTs and their mixtures. Osteoblast RNA was extracted for sintering cDNA to amplify genes of interest by PCR; intra- and extracellular calcium (Ca2+) was also quantified. Regarding the genes that participate in the regulation paths (MAPK and NF-KB), it was found that only the expression of NF-KB was affected in all treatments. The expression of VEGFA increased, except in the treatment of high concentration of MWCNTs, where remained unchanged. The expression of genes Apaf-1 and Bcl-2/Bax and TP53 increased as compared to the control (except for TP53 in BC and C1/MWCNTs) indicating that cells are responding to the presence of BCN-MWCNTs composites scaffolds. The results suggest that osteoblast developed a modification in the expression profile of genes that actively participate in cellular processes such as proliferation, vasculogenesis and apoptosis, which may be modulated by the increase of intra- and extracellular Ca2+ concentration.
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Celulose , Nanotubos de Carbono , Apoptose , Osteoblastos , TranscriptomaRESUMO
Epithelial ovarian cancer (EOC) is a lethal gynecological neoplasia characterized by extensive angiogenesis and overexpression of nerve growth factor (NGF). Here, we investigated the mechanism by which NGF increases vascular endothelial growth factor (VEGF) expression and the vasculogenic potential of EOC cells, as well as the contribution of the cyclooxygenase 2/prostaglandin E2 (COX-2/PGE2) signaling axis to these events. EOC biopsies and ovarian cell lines were used to determine COX-2 and PGE2 levels, as well as those of the potentially pro-angiogenic proteins c-MYC (a member of the Myc transcription factors family), survivin, and ß-catenin. We observed that COX-2 and survivin protein levels increased during EOC progression. In the EOC cell lines, NGF increased the COX-2 and PGE2 levels. In addition, NGF increased survivin, c-MYC, and VEGF protein levels, as well as the transcriptional activity of c-MYC and ß-catenin/T-cell factor/lymphoid enhancer-binding factor (TCF-Lef) in a Tropomyosin receptor kinase A (TRKA)-dependent manner. Also, COX-2 inhibition prevented the NGF-induced increases in these proteins and reduced the angiogenic score of endothelial cells stimulated with conditioned media from EOC cells. In summary, we show here that the pro-angiogenic effect of NGF in EOC depends on the COX-2/PGE2 signaling axis. Thus, inhibition COX-2/PGE2 signaling will likely be beneficial in the treatment of EOC.
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Statins may precipitate the onset of type 2 diabetes (T2D) in high-risk patients. In contrast, only the subset of individuals with insulin resistance and/or diabetes receives cardiovascular benefits with fibrates. In this context, previous observations from our laboratory suggested that atorvastatin induced an increase in visceral adipose tissue (VAT), whereas fenofibrate had the opposite effects in rabbits. Therefore, we determined the mass, morphology, and vascularization of VAT in New Zealand white rabbits (n = 6/group) that received 0.33 or 2.6 mg/kg/d of atorvastatin or fenofibrate, respectively, during 2 months. As expected, the cholesterol from the atorvastatin group was lower after treatment, while triglycerides decreased in the fenofibrate group. The mass of VAT from the fenofibrate group was 46% lower compared to the controls, meanwhile atorvastatin was associated with a larger diameter of adipocytes (+65%) than that of the control and fenofibrate groups. Fibroblast growth factor 2 (FGF2) gene expression was lower in the fenofibrate group than in the control group (-54%). By contrast, vascular endothelial growth factor A (VEGF-A) gene expression in fenofibrate-treated rabbits was 110% higher than in the control group. In agreement with the gene expression, the marker of angiogenesis platelet endothelial cell adhesion molecule 1 was slightly but significantly higher (+10%) in rabbits treated with fenofibrate than in controls, as determined by immunohistochemistry. These results suggest that fenofibrate is associated with a favorable remodeling of VAT, that is, reduced mass and increased vascularization in normolipemic rabbits; in contrast, atorvastatin induced a nonfavorable remodeling of VAT. These results may be related to the cardiovascular benefits of fenofibrate and the increased risk of T2D in high-risk patients induced by atorvastatin.
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Adipócitos/efeitos dos fármacos , Adiposidade/efeitos dos fármacos , Atorvastatina/farmacologia , Fenofibrato/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipolipemiantes/farmacologia , Gordura Intra-Abdominal/irrigação sanguínea , Gordura Intra-Abdominal/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Colesterol/sangue , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Gordura Intra-Abdominal/metabolismo , Masculino , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Coelhos , Transdução de Sinais , Triglicerídeos/sangue , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: We have previously demonstrated that acidic preconditioning of human endothelial colony-forming cells (ECFC) increased proliferation, migration, and tubulogenesis in vitro, and increased their regenerative potential in a murine model of hind limb ischemia without baseline disease. We now analyze whether this strategy is also effective under adverse conditions for vasculogenesis, such as the presence of ischemia-related toxic molecules or diabetes, one of the main target diseases for cell therapy due to their well-known healing impairments. METHODS: Cord blood-derived CD34+ cells were seeded in endothelial growth culture medium (EGM2) and ECFC colonies were obtained after 14-21 days. ECFC were exposed at pH 6.6 (preconditioned) or pH 7.4 (nonpreconditioned) for 6 h, and then pH was restored at 7.4. A model of type 2 diabetes induced by a high-fat and high-sucrose diet was developed in nude mice and hind limb ischemia was induced in these animals by femoral artery ligation. A P value < 0.05 was considered statistically significant (by one-way analysis of variance). RESULTS: We found that acidic preconditioning increased ECFC adhesion and the release of pro-angiogenic molecules, and protected ECFC from the cytotoxic effects of monosodium urate crystals, histones, and tumor necrosis factor (TNF)α, which induced necrosis, pyroptosis, and apoptosis, respectively. Noncytotoxic concentrations of high glucose, TNFα, or their combination reduced ECFC proliferation, stromal cell-derived factor (SDF)1-driven migration, and tubule formation on a basement membrane matrix, whereas almost no inhibition was observed in preconditioned ECFC. In type 2 diabetic mice, intravenous administration of preconditioned ECFC significantly induced blood flow recovery at the ischemic limb as measured by Doppler, compared with the phosphate-buffered saline (PBS) and nonpreconditioned ECFC groups. Moreover, the histologic analysis of gastrocnemius muscles showed an increased vascular density and reduced signs of inflammation in the animals receiving preconditioned ECFC. CONCLUSIONS: Acidic preconditioning improved ECFC survival and angiogenic activity in the presence of proinflammatory and damage signals present in the ischemic milieu, even under high glucose conditions, and increased their therapeutic potential for postischemia tissue regeneration in a murine model of type 2 diabetes. Collectively, our data suggest that acidic preconditioning of ECFC is a simple and inexpensive strategy to improve the effectiveness of cell transplantation in diabetes, where tissue repair is highly compromised.
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Ácidos/química , Diabetes Mellitus Experimental/tratamento farmacológico , Células Progenitoras Endoteliais/metabolismo , Glucose/metabolismo , Neovascularização Fisiológica/fisiologia , Animais , Diferenciação Celular , Proliferação de Células , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos NusRESUMO
This manuscript describes the experimental observation of vasculogenesis in chick embryos by means of network analysis. The formation of the vascular network was observed in the area opaca of embryos from 40 to 55 h of development. In the area opaca endothelial cell clusters self-organize as a primitive and approximately regular network of capillaries. The process was observed by bright-field microscopy in control embryos and in embryos treated with Bevacizumab (Avastin®), an antibody that inhibits the signalling of the vascular endothelial growth factor (VEGF). The sequence of images of the vascular growth were thresholded, and used to quantify the forming network in control and Avastin-treated embryos. This characterization is made by measuring vessels density, number of cell clusters and the largest cluster density. From the original images, the topology of the vascular network was extracted and characterized by means of the usual network metrics such as: the degree distribution, average clustering coefficient, average short path length and assortativity, among others. This analysis allows to monitor how the largest connected cluster of the vascular network evolves in time and provides with quantitative evidence of the disruptive effects that Avastin has on the tree structure of vascular networks.
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Helicobacter pylori is a pathogen involved in gastric diseases such as ulcers and carcinomas. H. pylori's urease is an important virulence factor produced in large amounts by this bacterium. In previous studies, we have shown that this protein is able to activate several cell types like neutrophils, monocytes, platelets, endothelial cells, and gastric epithelial cells. Angiogenesis is a physiological process implicated in growth, invasion and metastization of tumors. Here, we have analyzed the angiogenic potential of H. pylori urease (HPU) in gastric epithelial cells. No cytotoxicity was observed in AGS, Kato-III, and MKN28 gastric cell lines treated with 300 nM HPU, as evaluated by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. As we previously reported in neutrophils, treatment with 300 nM HPU also had an anti-apoptotic effect in gastric epithelial cells leading to a 2.2-fold increase in the levels of Bcl-XL after 6 h, and a decrease of 80% in the content of BAD, after 48 h, two mitochondrial proteins involved in regulation of apoptosis. Within 10 min of exposure, HPU is rapidly internalized by gastric epithelial cells. Treatment of the gastric cells with methyl-ß-cyclodextrin abolished HPU internalization suggesting a cholesterol-dependent process. HPU induces the expression of pro-angiogenic factors and the decrease of expression of anti-angiogenic factors by AGS cells. The angiogenic activity of HPU was analyzed using in vitro and in vivo models. HPU induced formation of tube-like structures by human umbilical vascular endothelial cells in a 9 h experiment. In the chicken embryo chorioallantoic membrane model, HPU induced intense neo-vascularization after 3 days. In conclusion, our results indicate that besides allowing bacterial colonization of the gastric mucosa, H. pylori's urease triggers processes that initiate pro-angiogenic responses in different cellular models. Thus, this bacterial urease, a major virulence factor, may also play a role in gastric carcinoma development.
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The C-X-C motif ligand 14 (CXCL14) is a recently discovered chemokine that is highly conserved in vertebrates and expressed in various embryonic and adult tissues. CXCL14 signaling has been implicated to function as an antiangiogenic and anticancer agent in adults. However, its function during development is unknown. We previously identified novel expression of CXCL14 mRNA in various ocular tissues during development. Here, we show that CXCL14 protein is expressed in the anterior eye at a critical time during neurovascular development and in the retina during neurogenesis. We report that RCAS-mediated knockdown of CXCL14 causes severe neural defects in the eye including precocious and excessive innervation of the cornea and iris. Absence of CXCL14 results in the malformation of the neural retina and misprojection of the retinal ganglion neurons. The ocular neural defects may be due to loss of CXCL12 modulation since recombinant CXCL14 diminishes CXCL12-induced axon growth in vitro. Furthermore, we show that knockdown of CXCL14 causes neovascularization of the cornea. Altogether, our results show for the first time that CXCL14 plays a critical role in modulating neurogenesis and inhibiting ectopic vascularization of the cornea during ocular development.
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Padronização Corporal , Quimiocinas CXC/metabolismo , Olho/embriologia , Olho/metabolismo , Técnicas de Silenciamento de Genes , Sistema Nervoso/irrigação sanguínea , Sistema Nervoso/embriologia , Animais , Padronização Corporal/genética , Galinhas , Córnea/inervação , Córnea/metabolismo , Substância Própria/metabolismo , Epitélio Corneano/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Iris/embriologia , Iris/inervação , Modelos Biológicos , Codorniz , RNA Interferente Pequeno/metabolismo , Retina/patologia , Nervo Trigêmeo/embriologia , Nervo Trigêmeo/metabolismoRESUMO
A pesar de los avances en el conocimiento clinicoepidemiológico de la obesidad, la prevalencia de esta ha aumentado significativamente, y su prevención y tratamiento continúa siendo un reto para los profesionales de la salud. Actualmente se considera que el control del balance energético se basa en un sistema de retroalimentación, cuyo objetivo es mantener los depósitos energéticos estables, a fin de lograr, con la disminución de peso, importantes beneficios en términos de salud y calidad de vida. En el presente trabajo se exponen algunas consideraciones relacionadas con la etiopatogenia de la obesidad y la importancia de la reducción de peso en los pacientes obesos(AU)
In spite of the advances in the clinical and epidemiological knowledge on obesity, its prevalence has increased significantly, and its prevention and treatment continue to be a challenge for the health professionals. At present it is considered that the control of the energy balance is based on a feedback system which objective is to maintain the stable energy deposits, in order to achieve, with the decrease of weight, important benefits in terms of health and life quality. In this work, some considerations related to the etiopatogenicity of obesity and the importance of weight reduction in the obese patients are exposed(AU)
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Humanos , Feminino , Gravidez , Eclampsia/fisiopatologia , Pré-Eclâmpsia/fisiopatologia , Hipertensão Induzida pela Gravidez , Genômica , ProteômicaRESUMO
La preeclampsia constituye una enfermedad de origen obstétrico que implica un aumento de la morbilidad y la mortalidad materna y perinatal. A tales efectos se llevó a cabo una extensa revisión bibliográfica con el fin de exponer las teorías más actualizadas en relación con la fisiopatología de la preeclampsia, que será un material de consulta valioso para los obstetras, quienes profundizarán en la génesis de la enfermedad, lo cual repercute en la toma de mejores decisiones.
Preeclampsia constitutes a disease of obstetric origin that implies an increase of the maternal and perinatal morbidity and mortality. To such effects an extensive literature review was carried out with the purpose of exposing the most updated theories in relation to the pathophysiology of preeclampsia that will be a valuable material for the obstetricians who will deepen in the genesis of the disease, which rebounds in a better decision making.
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Pré-Eclâmpsia/fisiopatologia , Eclampsia , Genômica , Proteômica , Neovascularização PatológicaRESUMO
Several studies have reported about the effects of magnetic fields (MFs) on vascular tissue. Extremely low frequency magnetic fields (ELF-MFs) can promote either inhibition or stimulation of vasculogenesis and angiogenesis, depending upon the intensity and time of exposure to the MF. To investigate the possible effects of ELF-MF on vascular processes, it is necessary to employ methods that allow parameterization of the vascular network. Vascular network is a structure with fractal geometry; therefore, fractal methods have been used to evaluate its morphometric complexity. Here, we used the lacunarity parameter (complementary method of fractal analysis) and multifractal analyses to investigate angiogenesis and vasculogenesis in the embryonic yolk sac membrane (YSM) of Japanese quails (Coturnix japonica) with and without exposure to an external MF of 1 mT and 60 Hz. Lacunarity results showed that the vascular density was lower for the group exposed to the magnetic field for 9 h/day. In addition, multifractal analysis showed reduced vascularization in the experimental groups (6 h/day and 9 h/day of exposure to MF). Furthermore, multifractal analysis showed difference between the groups exposed for 12 and 24 h/day. Using multifractal methods (generalized dimensions and singularity spectrum), it was possible to characterize the vascular network of the quail embryo YSM as a multifractal object, therefore proving this method to be a more appropriate application than the traditional monofractal methods.
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Vasos Sanguíneos/embriologia , Coturnix/embriologia , Campos Magnéticos , Saco Vitelino/irrigação sanguínea , Animais , Embrião não Mamífero/irrigação sanguínea , Embrião não Mamífero/efeitos da radiação , Fractais , Modelos Estatísticos , Neovascularização Patológica , Probabilidade , Radiação não Ionizante , Fatores de Tempo , Saco Vitelino/efeitos da radiaçãoRESUMO
INTRODUCTION: Microangiopathy and endothelial dysfunction are present in the early stages of systemic sclerosis (SSc). Defective vasculogenesis mediated by bone marrow-derived endothelial progenitor cells (EPCs) might be involved in the vascular abnormalities found in SSc. OBJECTIVES: To evaluate the circulating EPC levels and EPC subtypes via flow cytometry and early outgrowth colony-forming units (CFUs) in patients with SSc compared to healthy subjects. METHODS: Thirty-nine female SSc patients (30 in the early stages of SSc) and 44 age-matched healthy women were included. Peripheral blood EPCs were quantified using flow cytometry and by counting the early outgrowth CFUs. RESULTS: The EPCs quantified with flow cytometry and the CFU numbers were significantly lower in SSc patients than in control subjects (155.1 ± 95.1 vs. 241.3 ± 184.2 EPC/10(6) lymphomononuclear cells, p=0.011; 15.4 ± 8.6 vs. 23.5 ± 10.9 CFU, p<0.001; respectively), as well as in the group of patients in the early stages of SSc compared to the controls. Patients with digital ulcers had significantly higher CFU counts than those without ulcers (p=0.013). Among patients with the scleroderma pattern on nailfold capillaroscopy, patients with the late pattern had significantly lower EPC levels than those with the early and active patterns (p=0.046). There were no significant correlations of EPCs or CFU levels with RP duration. CONCLUSIONS: The present study revealed decreased EPCs in SSc patients, including those with early disease onset. These findings suggest that defective vasculogenesis occurs in the early phases of the disease. Therefore, EPCs might be an important therapeutic target for the prevention of vascular complications in SSc patients.
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Células Progenitoras Endoteliais/citologia , Escleroderma Sistêmico/patologia , Adulto , Estudos de Casos e Controles , Endotélio Vascular/fisiopatologia , Feminino , Citometria de Fluxo , Humanos , Leucócitos Mononucleares/citologia , Microcirculação , Angioscopia Microscópica , Pessoa de Meia-Idade , Doença de Raynaud/sangue , Doença de Raynaud/fisiopatologia , Escleroderma Sistêmico/sangue , Células-TroncoRESUMO
The formation of the coronary vasculature is a fundamental event in heart development and involves a series of carefully regulated temporal events that include vasculogenesis and angiogenesis. This review focuses the knowledge concerning the formation of the coronary arteries available so far and some molecular mechanisms involved in this process. Understanding coronary embryogenesis is important for interventions regarding adult cardiovascular diseases as well as those necessary to correct heart congenital defects. The insight of the coronary artery development as a result of ingrowth changed the understanding of several congenital coronary artery variations and anomalies described in gross anatomy.
La formación de la vascularización coronaria es un acontecimiento fundamental en el desarrollo del corazón e implica una serie de eventos temporales cuidadosamente regulados que incluyen vasculogénesis y angiogénesis. Esta revisión se focaliza en el conocimiento sobre la formación de las arterias coronarias y algunos mecanismos moleculares implicados en este proceso. Entender la embriogénesis coronaria es importante para las intervenciones relacionadas con las enfermedades cardiovasculares en los adultos, así como también, para corregir defectos congénitos del corazón. La idea del desarrollo de la arteria coronaria, como resultado del crecimiento interno, cambió la comprensión de diversas variaciones y anomalías congénitas de estas arterias descritas en la anatomía macroscópica.
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Humanos , Masculino , Feminino , Vasos Coronários/anatomia & histologia , Vasos Coronários/embriologia , Vasos Coronários/ultraestrutura , Morfogênese/genética , Neovascularização Fisiológica/fisiologiaRESUMO
Tipo de Estudio: retrospectivo, descriptivo. Objetivo: identificar los factores de riesgo y su influencia en la retinopatía del prematuro (ROP). Método: Se tomaron 74 recién nacidos pretérmino en el hospital Gineco-Obstétrico Enrique C. Sotomayor con factores de riesgo conocidos y se les realizó el examen de fondo de ojo mediante oftalmoscopía indirecta entre la cuarta y octava semanas de vida extrauterina; y sus respectivos controles hasta el alta oftalmológica. Resultados: de la población estudiada, 48 pacientes completaron los controles sin presentar la patología, y los 25 pacientes restantes (34) presentaron ROP en distintos grados. Tomando en cuenta los factores de riesgo estudiados y su repercusión sobre la patología: -La edad gestacional promedio de neonatos afectos fue de 32.8 semanas. -Tiempo promedio de exposición a oxigenoterapia de 10 días. -Promedio de peso al nacer 1325.5 gramos. Conclusiones: en este estudio la inmadurez neonatal fue el factor más determinante en la incidencia de esta patología, seguido del bajo peso al nacer y del tiempo de exposición a oxigenoterapia; y dado el gran numero de nacimientos pretérmino en el mundo y mayor aun en países en desarrollo como el nuestro, es menester hacer hincapié en la necesidad de una correcta implementación y organización interhospitalaria del programa de detección temprana de Retinopatía del Prematuro en nuestra ciudad, y de esta manera evitar el inicio de una vida en penumbra.
Type of study: Retrospective, descriptive. Objective: Identify the risk factors and its influence in retinopathy in premature patients. Method: A total of 74 preterm newborn at the Enrique C. Sotomayor Gineo-Obstetric Hospital with known risk factors were included in the study. They underwent an indirect ophtalmoscopy between the fourth and eight week of life and were monitored. Results: From the total population, 48 patients did not have symptoms of the pathology while being monitored and 25 patients left (34) had different stages of retinopathy. Our findings were: The average gestational age of the neonates was 32.8 weeks, the average time of oxygen therapy was 10 days and the average weight was 1325.5 grams. Conclusions: In this study prematurity was the factor that determined the incidence of the pathology, followed by low birth weight and the period received oxygen therapy. Due to the high incidence of premature births in the world and even higher in third world countries like ours it is important to organize a program for the early detection of retinopathy in premature newborns.