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OBJECTIVE: To assess the utility of the Curaçao criteria by age over time in children with hereditary hemorrhagic telangiectasia (HHT). STUDY DESIGN: This was a single-center, retrospective analysis of patients attending the HHT clinic at the Hospital for Sick Children (Toronto, Canada) between 2000 and 2019. The evaluation of the Curaçao criteria was completed during initial and follow-up visits. Screening for pulmonary and brain arteriovenous malformations was completed at 5 yearly intervals. RESULTS: A total of 116 patients with genetic confirmation of HHT were included in the analysis. At initial screening at a median (IQR) age of 8.4 (2.8, 12.9) years, 41% met criteria for a definite clinical diagnosis (≥3 criteria). In children <6 years at presentation, only 23% fulfilled at least 3 criteria initially. In longitudinal follow-up, 63% reached a definite clinical diagnosis, with a median (IQR) follow-up duration of 5.2 (3.2, 7.9) years (P = .005). Specifically, more patients met the epistaxis and telangiectasia criteria at last visit compared with initial (79% vs 60%; P = .006; 47% vs 30%; P = .02) but not for the arteriovenous malformation criterion (59% vs 57%; P = .65). CONCLUSIONS: In the pediatric population, most patients do not meet definite clinical criteria of HHT at initial presentation. Although the number of diagnostic criteria met increased over time, mainly due to new onset of epistaxis and telangiectasia, accuracy remained low during follow-up visits. Relying solely on clinical criteria may lead to underdiagnosis of HHT in children.

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SUMMARY Objective: The aim of this study was to evaluate the expression of endoglin and its correlation with histopathological and clinical findings in conjunctival nevi. Methods: The study included archival formalin-fixed, paraffin-embedded tissue sections of 44 patients with conjunctival nevi. Immunohistochemical staining for CD105 had been performed with monoclonal mouse antihuman CD105 antibodies. The intratumoral microvessel density for quantification of tumoral vascularization had been determined by this marker. Results: The expression of CD105 was positive in 30 (68.2%) cases. There was a statistically significant difference in the level of CD105 expression regarding the histological type of nevus (p=0.03) and intralesional cysts status (p=0.02). Spearman's rho (ρ −0.316) revealed a significant negative correlation between the expression of endoglin and the histological type of nevus (p=0.03) and between the expression of endoglin and the presence of intralesional cysts (ρ −0.380, p=0.01). Conclusion: This study suggests that endoglin could be a useful diagnostic and prognostic marker in differentiating between benign and malignant melanocytic ocular lesions.

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Resumen ANTECEDENTES: La telangiectasia hemorrágica hereditaria, o síndrome de Rendu-Osler-Weber, es una enfermedad vascular, hereditaria y autosómica caracterizada por telangiectasias mucocutáneas y malformaciones arteriovenosas en el pulmón, el cerebro e hígado. La prevalencia estimada es de 1.5 a 2 personas afectadas por cada 10,000 habitantes. El 90% de los casos se debe a una mutación en el gen endoglina y en el de la cinasa 1 similar al receptor de activina (ACVRL1). En la mujer embarazada, la telangiectasia hemorrágica hereditaria es de alto riesgo, sobre todo durante el segundo y tercer trimestre. OBJETIVO: Reportar un caso de telangiectasia hemorrágica hereditaria y exponer las complicaciones que pueden registrarse durante el embarazo. CASO CLÍNICO: Paciente de 23 años, con antecedente heredofamiliar de madre con diagnóstico de telangiectasia hemorrágica hereditaria (síndrome de Osler-Weber-Rendu) que falleció a los 38 años. Antecedente personal patológico de telangiectasia hemorrágica hereditaria, con diagnóstico a los 12 años luego de múltiples episodios de epistaxis. Recibió tratamiento con transfusiones sanguíneas en múltiples ocasiones y 200 mg de sulfato ferroso cada 24 horas. CONCLUSIÓN: La telangiectasia hemorrágica hereditaria condiciona, en la mujer embarazada, la aparición de complicaciones que pueden poner en riesgo la vida de la madre y el feto. Las mujeres con antecedente conocido deben valorarse antes de la concepción con el propósito de conocer el estado de la enfermedad.

Abstract BACKGROUND: Hereditary hemorrhagic telangiectasia, or Rendu-Osler-Weber syndrome, is an autosomal inherited vascular disease characterized by mucocutaneous telangiectasias and arteriovenous malformations in the lung, brain and liver. The estimated prevalence is 1.5 to 2 affected persons per 10,000 population. Ninety percent of cases are due to a mutation in the endoglin gene and in the activin receptor-like kinase 1 gene (ACVRL1). In pregnant women, hereditary hemorrhagic telangiectasia is high risk, especially during the second and third trimester. OBJECTIVE: To report a case of hereditary hemorrhagic telangiectasia and to expose the complications that can occur during pregnancy. CLINICAL CASE: 23-year-old patient, with hereditary family history of mother diagnosed with hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) who died at 38 years of age. Personal pathological history of hereditary hemorrhagic telangiectasia, diagnosed at the age of 12 years after multiple episodes of epistaxis. She was treated with multiple blood transfusions and 200 mg of ferrous sulfate every 24 hours. CONCLUSION: Hereditary hemorrhagic telangiectasia conditions, in pregnant women, the appearance of complications that can put the life of the mother and fetus at risk. Women with a known history should be evaluated before conception in order to know the status of the disease.

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INTRODUCTION: Gestational hypertension (GH) pregnancies are at a high risk of developing adverse outcomes, including progression to preeclampsia. Prediction of GH-related adverse outcomes is challenging because there are no available clinical tests that may predict their occurrence. OBJECTIVE: The aim of the study was to determine the clinical usefulness of the soluble endoglin (sEng) and parameters of uterine artery flow (UtAF) measured by Doppler ultrasonography as markers of progression to preeclampsia in women with GH. SETTING: Mexico City, Mexico. MATERIAL AND METHODS: We included 77 singleton pregnant women with GH in a nested case-control study. Cases were women who progressed to preeclampsia (n = 36), and controls were those who did not (n = 41). Serum sEng and UtAF measurements were performed at enrollment. The main outcomes measured were progression to preeclampsia and occurrence of preterm delivery (PD) <37 and <34 weeks of gestation, small for gestational age infant (SGA), and fetal growth restriction (FGR). RESULTS: Women with sEng values in the highest tertile had higher risk of progression to preeclampsia, preterm delivery <34 weeks of gestation, and fetal growth restriction, odds ratios (ORs) ≥3.7. Patients with abnormal UtAF Dopp-ler-pulsatility index had higher risk of progression to preeclampsia, preterm delivery <34 weeks of gestation, small for gestational age infant, and fetal growth restriction (ORs ≥3.3). The presence of notch was associated with higher risk of progression to preeclampsia, preterm delivery <37 and <34 weeks of gestation, SGA infant, and fetal growth restriction (ORs ≥2.9). However, logistic regression analysis revealed that only serum sEng was a significant and independent risk factor for progression of GH to preeclampsia, preterm delivery <34 weeks of gestation, and fetal growth restriction (ORs ≥3.1). CONCLUSIONS: In GH pregnancies, UtAF Doppler ultrasonography is associated with increased risk of adverse outcomes and progression to preeclampsia. However, serum sEng concentration appears to be a better predictor to assess the risk of adverse maternal and perinatal outcomes and progression to preeclampsia.

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Preeclampsia is characterized by an imbalance in angiogenic factors, including sEng (soluble endoglin). However, the relationship of sEng with the severity of preeclampsia, clinical, and laboratory parameters, and the occurrence of adverse outcomes are not fully elucidated. We studied 1002 women with preeclampsia. Serum concentrations of sEng were measured by ELISA. Serum sEng levels were significantly different (P<0.001) in patients with preeclampsia than in healthy pregnancy. In addition, these factors were markedly different in patients with hemolysis, elevated liver enzymes, low platelet count syndrome and eclampsia than in patients with preeclampsia with or without severe features (P<0.001) and in patients with preeclampsia with severe features than in those without severe features (P<0.001). sEng correlated positively with blood pressure, proteinuria, and levels of creatinine, uric acid, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase; and inversely with gestational age, infant's birth weight, and platelets counts (P<0.001 for all). The risk of combined and specific adverse outcomes (pulmonary edema, acute renal failure, placental abruption, hepatic hematoma or rupture, maternal death, cerebral hemorrhage, thrombocytopenia, elevated liver enzymes, preterm delivery, small for gestational age infant, and need for endotracheal intubation, positive inotropic drug support, and hemodialysis) was higher in patients with sEng values in the highest quartile (odds ratio ≥3.1) compared with the lowest quartile. Patients in the highest quartile of sEng were more likely to deliver early compared with those in the lowest quartile (HR, 2.33; 95% CI, 1.91-2.84). We concluded that circulating concentrations of sEng seem to be a suitable marker to assess the severity of preeclampsia and are associated with increased risk of adverse outcomes.

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Introdução: a endoglina (ENG, CD105) é um co-receptor da família transforming growth factor-beta e participa da regulação de processos celulares como proliferação, diferenciação, migração e apoptose. ENG é mais conhecida por sua expressão em células endoteliais, desempenhando papel importante na angiogênese e vasculogênese, porém sua expressão já foi associada a diferentes desfechos patogênicos, inclusive devido a mutações no gene ENG. Objetivos: descrever a frequência de variantes genéticas no gene ENG, comparar com populações ancestrais e analisar as variantes genéticas que possam estar envolvidas em processos patogênicos em outras populações. Metodologia: foi utilizado o banco de dados do programa SCAALA (Social Change Asthma and Allergy in Latin America) para a população do estudo, sendo genotipado 1309 indivíduos usando o chip Illumina 2.5 Human Omni Bead e feitas análises in silico utilizando plataformas on-line. Resultados: as variantes genéticas rs10987746, rs10121110, rs11792480 e rs16930129 apresentaram frequência de menor alelo entre 16 a 48% na população estudada, as quais foram mais reiteradamente próximas do padrão africano que do europeu. Os SNVs foram relacionados aos mecanismos regulatórios genéticos conhecidos, pressupondo que essas variantes não estejam envolvidas diretamente em processos funcionais. Conclusão: são necessárias maiores investigações referentes aos mecanismos funcionais deste gene, visto que a endoglina participa de uma gama de processos celulares importantes e mais esforços devem ser feitos para estudos genéticos na população brasileira, considerando a mistura de populações.

Introduction: the endoglin (ENG, CD105) is a coreceptor of the family transforming growth factor-beta and participates in the regulation of cellular processes such as proliferation, differentiation, migration and apoptosis. ENG She is best known for your expression in endothelial cells, playing an important role in angiogenesis and vasculogenesis, but its expression has already been associated with different pathogenic outcomes, including due to mutations in the ENG gene. Objectives: describe the frequency of genetic variants in the ENG gene in the population of northeastern Brazil, compare with ancestral populations and analyze genetic variants that may be involved in pathogenic processes in other populations. Methodology: we used the SCAALA program database (Social Change Asthma and Allergy in Latin America) for the population of the study, and the DNA of 1309 individuals were genotyped using the Illumina chip 2.5 Human Omni Bead and made in silico analysis. Results: the SNVs rs10987746, rs10121110, rs11792480 and rs16930129 presented lower allele frequency between 16 to 48% in the population studied, which were more consistently next African European standard. The SNVs were related to known genetic regulatory mechanisms assuming that these variants are not directly involved in functional processes. Conclusion: further investigation regarding the functional mechanisms of this gene are necessary, since the endoglin participates in a range of important cellular processes and more efforts should be made for genetic studies in the Brazilian population, considering the mixture of populations.

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BACKGROUND: Primary cultures endothelial cells have been used as models of endothelial related diseases such atherosclerosis. Biological behavior of primary cultures is donor-dependent and data could not be easily reproducible; endothelial cell lines are emerging options, particularly, human dermal microvascular endothelial cells (HMEC-1), that should be validated to substitute primary cultures for the study of HDL functions. METHODS: Morphology, size and granularity of cells were assessed by phase contrast microscopy and flow cytometry of HMEC-1. The adhesion molecules, ICAM-1and VCAM-1 after TNF-α stimulation, and endothelial markers CD105 endoglin, as well as HDL receptor SR-BI were determined by flow cytometry. Internalization of HDL protein was demonstrated by confocal microscopy using HDL labeled with Alexa Fluor 488. HUVECs were used as reference to compared the characteristics with HMEC-1. RESULTS: HMEC-1 and HUVEC had similar morphologies, size and granularity. HMEC-1 expressed endothelial markers as HUVECs, as well as functional SR-B1 receptor since the cell line was able to internalize HDL particles. HMEC-1 effectively increased ICAM-1 and VCAM-1 expression after TNF-α stimulation. HUVECs showed more sensibility to TNF-α stimulus but the range of ICAM-1 and VCAM-1 expression was less homogeneous than in HMEC-1, probably due to biological variation of the former. Finally, the expression of adhesion molecules in HMEC-1 was attenuated by co-incubation with HDL. CONCLUSION: HMEC-1 possess characteristics of endothelial cells, similar to HUVECs, being a cell line suitable to evaluate the functionality of HDL vis-à-vis the endothelium.

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BACKGROUND: Pre-eclampsia is a multifactorial hypertensive disorder that is triggered by placental insufficiency and that accounts for up to 15% of maternal deaths. In normal pregnancies, this process depends on the balance between the expression of angiogenic factors and antiangiogenic factors, which are responsible for remodeling the spiral arteries, as well as for neoangiogenesis and fetal development. PURPOSE: The aim of this review is to discuss the main scientific findings regarding the role of angiogenic and antiangiogenic factors in the etiopathogenesis of preeclampsia. METHODS: An extensive research was conducted in the Pubmed database in search of scientific manuscripts discussing potential associations between angiogenic and antiangiogenic factors and preeclampsia. Ninety-one papers were included in this review. RESULTS: There is an increased expression of soluble fms-like tyrosine kinase receptor and soluble endoglin in pre-eclampsia, as well as reduced placental expression of vascular endothelial growth factor and placental growth factor. Systemic hypertension, proteinuria and kidney injury - such as enlargement and glomerular fibrin deposit, capillary occlusion due to edema, and hypertrophy of endocapillary cells - are some of these changes. The complex etiopathogenesis of preeclampsia instigates research of different biomarkers that allow for the early diagnosis of this entity, such as vascular endothelial growth factor, placental growth factor, soluble fms-like tyrosine kinase receptor, soluble endoglin, placental glycoprotein pregnancy-associated plasma protein-A and protein 13. CONCLUSION: Even though it is possible to establish an efficient and effective diagnostic tool, three key principles must be observed in the management of preeclampsia: prevention, early screening and treatment.

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PURPOSE: Endothelial barrier dysfunction is a hallmark of sepsis, and is at least partially mediated by pathways that regulate endothelial barrier assembly during angiogenesis. Not surprisingly, increased levels of key angiogenic proteins such as VEGF-A and Angiopoietin-2 have been described in sepsis. The purpose of this study was to investigate if additional pathways that regulate endothelial barrier integrity during angiogenesis could also be involved in the host response of sepsis. MATERIAL AND METHODS: We evaluated circulating levels of four proteins involved in angiogenesis, not previously studied in sepsis, in a cohort of 50 patients with severe sepsis and septic shock. RESULTS: Circulating levels of BMP-9 and FGF-2 were similar in patients and healthy volunteers. In contrast, patients with septic shock presented 1.5-fold higher levels of endoglin (P=0.004), and 2-fold lower levels of Heparin-Binding EGF-like growth factor (HB-EGF) (P=0.002) when compared to healthy individuals. Of note, HB-EGF deficiency has been recently demonstrated to be detrimental to survival in a murine model of sepsis. CONCLUSIONS: Endoglin and HB-EGF could be involved in the host response of sepsis. Additional studies are warrant to investigate their role as biomarker or therapeutic targets in sepsis.

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Radiofrequency (RF) treatment appears to be involved in production of new collagen fibrils and the improvement of existing collagen structures; however, the molecular bases of the effect of non-invasive RF on the skin tissue have not been fully elucidated. This study reports the effects of RF associated or not with hydrolyzed collagen (HC) in the skin tissue. Wistar rats were randomly divided into four groups, according to the treatment received: control group (G1, n = 5), no treatment; subjects in group G2 (n = 5) were treated with HC; and capacitive RF was applied to the back of each subject in G3 (n = 5) and RF associated with HC in G4 (n = 5). Biopsies were taken 30 days after treatment and then were histologically processed and studied for inflammatory cell counting, collagen content, and morphometry. In addition, FGF2, CD105, and COX-2 expression was assessed by immunohistochemical staining. The most relevant changes were the increase in cellularity and accumulation of intercellular substance in RF-treated animals (G3 and G4). The greatest dermis thickness rate was observed in G4, followed by G3 and G2 (p < 0.05). RF-treated skins (G3 and G4) exhibited a significant overexpression of FGF2 (p < 0.0001) and increased microvessel density (p < 0.0001) in comparison with G1 and G2. Moreover, the amount of COX-2 was significantly higher (p < 0.0001) in dermis of RF-treated areas compared to G1 and G2, and demonstrated differences in G3 (RF) compared to G4 (RF + HC) (p < 0.0001). Our results suggests that RF treatment associated or not with HC induces FGF2 overexpression, promotes neoangiogenesis and modulates the COX-2 expression, subsequently promotes neocollagenesis, and increased thickness rate of dermis.

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INTRODUCTION: The aim of this study was to reproducibly determine if any of the polymorphisms were associated with the susceptibility to brain arteriovenous malformations (BAVM) or the risk of intracranial hemorrhage (ICH) presentation. METHODS: We recruited 63 BAVM patients and 96 controls. The polymorphisms selected for evaluation were apolipoprotein E (APOE), tumor necrosis factor alpha (TNF 238G>A - rs361525), interleukin 1 beta (IL1B 511C>T - rs16944 and IL1B -31T>C - rs1143627), activin-like kinase 1 (ACVRL1 IVS3-35A>G - rs2071219), endoglin (ENG 207G>A - rs11545664), and interleukin 6 (IL6 174G>C - rs1800795). RESULTS: In the single analysis, we observed statistically significant differences in the allele distributions for IL1B -31T>C (rs1143627) between the BAVM patients and control subjects (P = 0.02). There was a trend toward significance for the association between the IL1B 511C>T (rs16944) allele and BAVM risk (P = 0.07). In further logistic regression analysis, no polymorphism was significantly associated with the risk of BAVM. No polymorphisms were associated with hemorrhage presentation according to both single and multivariable analyses. CONCLUSIONS: In our sample from a south Brazil population, we found no association between the risks of BAVM and ICH presentation with any of the selected polymorphisms.

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PURPOSE: Assessing the biochemical markers levels and the uterine artery Doppler (UtA) parameters in fetuses with growth restriction (FGR). METHODS: Prospective case-control study included 66 patients with diagnosis of FGR and 64 healthy pregnancies at 24-41 weeks of gestation. For both groups, maternal circulating concentrations of biochemical factors of soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin(sEng), adiponectin, A disintegrin and metalloproteinases (ADAM-12), pregnancy-associated plasma protein-A (PAPP-A), angiopoietin-2 (ANGI-2), vascular endothelial growth factor (VEGF) and transforming growth factor-ß (TGF-ß) were assayed by ELISA and UtA by Doppler were performed. ANOVA, Mann-Whitney tests and Pearson correlation coefficient were applied to compare the biochemical factors, UtA Doppler and EFW Z-score between the groups. RESULTS: Concentrations of sFlt-1, sEng, PAPP-A were significantly higher in FGR than controls (p < 0.0001, p = 0.02 and p = 0.03, respectively), but concentration of ANGI-2 (p < 0.0001) was significantly lower in FGR than controls and ADAM-12 levels had a tendency to be lower in the FGR, though not statistically significant (p = 0.059). Increased sEng concentrations were correlated with abnormal UtA Doppler in FGR. CONCLUSION: Fetal growth restriction fetuses showed increased serum levels of sFlt-1, sEng and PAPP-A with levels of ANGI-2 decreased and a positive association between elevated concentrations of sEng and changing impedance of UtA Doppler were observed.

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BACKGROUND: Preeclampsia (PE) is a multisystem disease characterized by the development of hypertension and proteinuria. Although PE etiology is not fully known, the placenta seems to play a central role in the development of disease. The inadequate placentation process results in a change in angiogenic factors levels, such as vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble form of endoglin (s-Eng) and soluble form of vascular endothelial growth factor receptor type 1 (sFlt-1). OBJECTIVE: The aim of this review was to clarify if the imbalance between pro-angiogenic and anti-angiogenic factors is associated with PE. CONCLUSION: It is known that inadequate placentation process is the primary mechanism suggested for PE occurrence and angiogenic factors are involved in this process. The state-of-the-art suggests that progress in grasp the imbalance of pro-angiogenic and anti-angiogenic factors is essential for the improvement of knowledge about PE. The development of prospective, longitudinal studies with serial determinations of these factors throughout pregnancy is needed to better assess the relevance of these markers for understanding the etiology, prevention, diagnosis, prognosis and treatment of this challenging disease.

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La participación de los factores antiangiogénicos, la forma soluble de la fms-semejante a la tirosina quinasa (Flt-1s) y la endoglina soluble (Engs), en el desarrollo de la preeclampsia (PE) se ha demostrado en múltiples estudios clínicos y experimentales. Estos estudios están complementados por estudios en animales, en los cuales la sobreexpresión de estos factores antiangiogénicos origina manifestaciones clínicas muy similares a la PE. El origen de esta enfermedad permanece desconocido. Sin embargo, factores genéticos, ambientales e inmunológicos parecen alterar el desarrollo normal de la placenta, lo cual conduce últimamente a la PE. Flt-1s y Engs inhiben la producción y las propiedades proangiogénicas del factor de crecimiento vascular endotelial (FCVE) y del factor de crecimiento placentario (FCP), necesarios para el desarrollo normal vascular de la placenta y las adaptaciones vasculares fisiológicas del embarazo. Cantidades exageradas de Flt-1s y Engs se producen en la placenta disfuncional y se liberan en la circulación materna. Altas concentraciones de Flt-1s y Engs se encuentran en la circulación materna semanas antes de que la enfermedad sea detectada clínicamente. Las capacidades de los factores angiogénicos para predecir PE en embarazos asintomáticos de riesgo bajo y alto son inconsistentes y no útiles para el uso clínico. Por otro lado, proporciones de los factores Flt-1s/FCP, FCP/Flt-1s, y FCP/Eng poseen valores predictivos más altos para diagnosticar PE y predecir sus complicaciones en mujeres con sintomatología de PE. En estas condiciones, el uso clínico de estos marcadores biológicos podría ser implementado en un futuro cercano. Las propiedades biológicas y farmacocinéticas de las estatinas las convierten en uno de los medicamentos con más potencial preventivo para la PE. Otros opciones terapéuticas que se están estudiando son medicamentos que directamente inhiban los factores antiangiogénicos circulantes. Estudios in vitro y estudios pilotos clínicos se están realizando actualmente examinando la seguridad materno-fetal, la transferencia placentaria y la efectividad de estas terapias.

The role of the antiangiogenic factors, the soluble form of the fms-like tyrosine kinase receptor 1 (sFlt1) and the soluble endoglin (sEng), in the development of preeclampsia (PE) has been demonstrated in multiple clinical and experimental studies. These studies are complemented by animal studies, in which overexpression of these antiangiogenic factors leads to clinical manifestations similar to PE. Although, the origin of this disease remains unknown, genetic, environmental, and immunological factors appear to affect the normal placental development, resulting ultimately in PE. sFlt-1 and sEng inhibit the proangiogenic properties of the vascular endothelial growth factor (VEGF) and the placental growth factor (PlGF), affecting the normal vascular development in the placenta and the physiological vascular adaptations that occur in pregnancy. Exaggerated amounts of sFlt-1 and sEng, produced in the dysfunctional placenta, are released into the maternal circulation and elevated circulating concentrations of these antiangiogenic factors are found several weeks prior to the clinical manifestations of the disease. Multiple studies have reported the capacity of circulating antiangiogenic factor concentrations to predict PE in asymptomatic low and high risk pregnancies. The reported predictive values of sFlt-1 and sEng are inconsistent across these studies and therefore their clinical use in this population is not recommended. On the other hand, maternal plasma concentrations of these factors appear to have a better performance in women with symptoms of PE. Among the possible combinations, the ratios of sFlt-1/PlGF, PlGF/sFlt-1, and PlGF/Engs seem to have the highest sensitivities and specificities to diagnose PE as well as the highest predictive values for PE-related adverse outcomes. These properties support their clinical use in this setting and it is likely those ancillary tests will be incorporated to the clinical practice in the near future. The participation of antiangiogenic factors in the pathogenesis of PE, also have stimulated investigation of new targeted therapies. The biological and pharmacokinetic properties of statins have converted them in one of the most promising preventive therapies for this disease. Others are investigating agents that directly inhibit the circulating antiangiogenic factors. In-vitro and pilot clinical studies are currently evaluating the effectiveness, maternal-fetal safety, and placental transference of these therapies.

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The typical characteristics of mesenchymal stem cells (MSCs) can be affected by inflammatory microenvironment; however, the exact contribution of HTLV-1 to MSC dysfunction remains to be elucidated. In this study, we demonstrated that MSC cell surface molecules VCAM-1 and ICAM-1 are upregulated by contact with HTLV-1, and HLA-DR was most highly expressed in MSCs co-cultured with MT2 cells. The expression levels of VCAM-1 and HLA-DR were increased in MSCs cultured in the presence of PBMCs isolated from HTLV-1-infected symptomatic individuals compared with those cultured with cells from asymptomatic infected individuals or healthy subjects. HTLV-1 does not impair the MSC differentiation process into osteocytes and adipocytes. In addition, MSCs were efficiently infected with HTLV-1 in vitro through direct contact with HTLV-1-infected cells; however, cell-free virus particles were not capable of causing infection. In summary, HTLV-1 can alter MSC function, and this mechanism may contribute to the pathogenesis of this viral infection.

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A angiogênese é um mecanismo fundamental para o desenvolvimento tumoral, sendo utilizada para fins de diagnóstico diferencial e determinação de prognóstico em várias neoplasias de cabeça e pescoço. Este trabalho se propôs avaliar a atividade angiogênica através da expressão imuno-histoquímica dos anticorpos anti-CD105 e anti-CD34 em 20 casos de hemangiomas e 20 casos de granulomas piogênicos orais, além de averiguar a utilidade destes marcadores como um dos recursos de diagnóstico diferencial para estas duas lesões orais. Os resultados deste experimento demonstraram que não houve diferença estatisticamente significativa entre as médias de contagem microvascular (MVC) determinadas pelos os anticorpos anti-CD105 (p=0,803) e anti-CD34 (p=0,279). O número médio dos vasos obtidos pela MVC nos espécimes de hemangiomas orais imunomarcados pelo anti-CD105 e anti-CD34 foram respectivamente 18,75 e 59,72, enquanto nos granulomas piogênicos orais, o número médio dos vasos obtidos pela MVC pelo anti-CD105 e anti-CD34 foram respectivamente 20,22 e 48,09. Foi verificado, também, que o CD34 foi mais efetivo na identificação de vasos sangüíneos quando comparado com o CD105. Entretanto, faz-se necessário destacar, que o anticorpo anti-CD105 parece estar mais relacionado com a neoformação vascular. Em linhas gerais, este ensaio reforça a participação dos fatores angiogênicos na etiopatogênese dos hemangiomas e granulomas piogênicos orais, porém os resultados mostraram que a quantificação da angiogênese não pode ser utilizada como parâmetro de diagnóstico diferencial entre as duas lesões analisadas. (AU)

Angiogenesis, a fundamental mechanism in tumor development, is used for differential diagnosis and prognosis purposes in various neoplasias of the head and neck. This study proposes to assess angiogenic activity using immunohistochemical expression by anti-CD105 and anti-CD34 antibodies in 20 cases of hemangiomas and 20 cases of oral pyogenic granulomas, in addition to determining the usefulness of these markers as one of the differential diagnosis resources for these two oral lesions. The results showed no statistically significant difference between microvascular count (MVC) means determined by anti-CD105 (p = 0.803) and anti-CD34 (p = 0.279) antibodies. The mean number of vessels obtained by MVC in the oral hemangiomas immunostained by anti-CD105 and anti-CD34 was 18.75 and 59.72, respectively, whereas in the oral pyogenic granulomas, the mean number was 20.22 and 48.09 respectively. It was also shown that CD34 was more effective than CD105 in identifying blood vessels. However, it must be pointed out that the anti-CD105 antibody seems to be more related to vascular neoformation. Overall, this assay reinforces the role of angiogenic factors in the etiopathogenesis of hemangiomas and oral pyogenic granulomas, but the results showed that angiogenesis quantification cannot be used as a differential diagnosis parameter between the two lesions analyzed. (AU)

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