The Essential Role of PGF2α/PTGFR in Molding Endometrial Breakdown and Vascular Dynamics, Regulated by HIF-1α in a Mouse Menstrual-like Model.

In women of childbearing age, extensive decidualization, shedding and remodeling of the endometrium during the menstrual cycle are fundamental for successful pregnancy. The role of prostaglandins (PGs) in menstruation has long been proposed in humans, and the rate-limiting enzyme cyclooxygenase was shown to play a key role in endometrial breakdown and shedding in a mouse menstrual-like model in our previous study. However, the specific types of PGs involved and their respective roles remain unclear. Therefore, our objective was to investigate the mechanism through which PGs regulate endometrial disintegration. In this study, the microscopy was observed by HE; the protein levels of prostaglandins E1 (PGE1), prostaglandins E2 (PGE2), prostaglandin F2α (PGF2α) and Prostaglandin I2 (PGI2) were detected by ELISA; the mRNA level of Pfgfr2, Vascular Endothelial Growth Factor(Vegf), Angiostatin and Hypoxia inducible factor-1α (Hif1α) were examined by real-time PCR; PTGFR Receptor (PTGFR), VEGF, Angiostatin and HIF-1α protein levels were investigated by western blotting; the locations of protein were observed by Immunohistochemistry; HIF-1α binding PTGFR promoter was detected by Chromatin Immunoprecipitation (ChIP) and real-time PCR. We found that the concentrations of PGE1, PGE2, and PGF2α all increased significantly during this process. Furthermore, Ptgfr mRNA increased soon after Progesterone (P4) withdrawal, and PTGFR protein levels increased significantly during abundant endometrial breakdown and shedding processes. PTGFR inhibitors AL8810 significantly suppressed endometrial breakdown and shedding, promoted Angiostatin expression, and reduced VEGF-A expressions and vascular permeability. And HIF-1α and PTGFR were mainly located in the luminal/gland epithelium, vascular endothelium, and pre-decidual zone. Interestingly, HIF-1α directly bound to Ptgfr promoter. Moreover, a HIF-1α inhibitor 2-methoxyestradiol (2ME) significantly reduced PTGFR expression and suppressed endometrial breakdown which was in accord with PTGFR inhibitor's effect. Similar changes occurred in human stromal cells relevant to menstruation in vitro. Our study provides evidence that PGF2α/PTGFR plays a vital role in endometrial breakdown via vascular changes that are regulated by HIF-1α during menstruation.

Estudo da Reatividade Microvascular em Pacientes Hipertensos com Adiposidade Corporal Elevada / Microvascular Reactivity in Hypertensive Patients with High Body Adiposity

Resumo Fundamento: Diversos índices antropométricos têm sido propostos para determinar a associação entre excesso de peso e fatores de risco cardiovascular. Objetivo: Avaliar a relação entre adiposidade corporal e reatividade microvascular em pacientes hipertensos sob terapia anti-hipertensiva. Métodos: Pacientes hipertensos tratados de 40 a 70 anos foram submetidos à avaliação de índices antropométricos: conicidade (IC), adiposidade corporal (IAC), adiposidade visceral (IAV) e relação cintura-estatura (RCE). Os participantes foram divididos pelos tercis de percentual de gordura (%G) obtido pela bioimpedância elétrica (BIA) e submetidos a teste de reatividade microvascular (laser speckle contrast image), medida da velocidade da onda de pulso (VOP). O valor de p < 0,05 foi considerado estatisticamente significativo. Resultados: A variação da área sob a curva (ASC) da perfusão cutânea foi inferior no tercil superior (97 ± 57% vs. 67 ± 36%; p = 0,027). O %G apresentou correlação significativa com RCE (r = 0,77; p < 0,001), IAV (r = 0,41; p = 0,018), IC (r = 0,60; p < 0,001) e IAC (r = 0,65; p < 0,001) nos homens e somente com RCE (r = 0,55; p < 0,001) e IAC (r = 0,60; p < 0,001) nas mulheres. Na regressão linear, a ASC mostrou associação independente com o %G (β =-3,15; p = 0,04) nas mulheres e com a glicemia (β = -1,15; p = 0,02) nos homens. Não houve diferença nas medidas de VOP. Conclusão: Os índices antropométricos de obesidade foram mais associados ao %G nos homens. A maior adiposidade corporal foi relacionada com menor reatividade microvascular, o que foi mais evidente nas mulheres. Não houve diferença na rigidez arterial, o que pode ter sido influenciado pelo tratamento anti-hipertensivo.

Abstract Background: Several anthropometric indexes have been proposed to determine the association between overweight and cardiovascular risk factors. Objective: To evaluate the relationship between body adiposity and microvascular reactivity in hypertensive patients under antihypertensive therapy. Methods: Treated hypertensive patients aged 40 to 70 were submitted to evaluation of anthropometric indexes: conicity (CI), body adiposity (BAI), visceral adiposity (VAI) and waist-to-height ratio (WHtR). Participants were divided by the terciles of fat percentage (%F) obtained by bioelectrical impedance. The patients underwent microvascular reactivity test (Laser Speckle Contrast Image) and pulse wave velocity (PWV) measurement. The p value <0.05 was considered statistically significant. Results: The variation of the area under the curve (AUC) of the skin perfusion was lower in the upper tercile (97±57% vs. 67±36%; p=0.027). %F showed significant correlation with WHtR (r=0.77; p<0.001), VAI (r=0.41; p=0.018), CI (r=0.60; p<0.001), BAI (r=0.65; p<0.001) in men and only with WHtR (r=0.55; p<0.001) and BAI (r=0.60; p<0.001) in women. In linear regression, AUC was independently associated with %F (β=−3.15; p=0.04) in women and with blood glucose (β=−1.15; p=0.02) in men. There was no difference in PWV measurements. Conclusion: Anthropometric indices were more associated with %F in men. Higher body adiposity was associated with lower microvascular reactivity, which was more evident in women. There was no difference in arterial stiffness, which may have been influenced by antihypertensive treatment.

Hypotension and bradycardia produced by transthoracic application of low-intensity ultrasound therapy in hearts of healthy rats - a preclinical study

Abstract Objective: To investigate the cardiovascular effects produced by transthoracic application of low-intensity pulsed ultrasound therapy (LIPUST). Methods: Three-month-old male Wistar rats (± 300 g, N=16) were randomly allocated in two groups, namely SHAM (control group, faked procedures) and UST (animals treated with LIPUST). These animals, under anesthesia, were instrumented (femoral artery and vein catheterization) for hemodynamic recordings (mean blood pressure [MBP], heart rate [HR]) and blood biochemical profile (lipids, creatine kinase-myocardial band [CK-MB]). Then, LIPUST (spatial average-temporal average [ISATA] 1-MHz, power 0.1 to 1.2 W/cm2, pulsed 2:8 ms, cycle at 30%, for three minutes) was applied to animals from the UST group, externally to their thorax. SHAM animals were equally manipulated, but without application of ultrasound energy. After the hemodynamic and biochemical measurements, animals were sacrificed, and their hearts were mounted in a Langendorff apparatus for coronary reactivity evaluation. Standard histology techniques were employed to analyze the hearts. Results: LIPUST application caused statistically significant reductions in MBP (92±4 vs. 106±1 mmHg) and HR (345±14 vs. 380±17 rpm) when compared with SHAM procedures. UST rats exhibited higher CK-MB levels (318±55 vs. 198±26 U/dL) and lower plasma triglycerides levels (38±7 vs. 70±10 mg/dL) than SHAM animals. Coronary reactivity was not significantly changed by LIPUST. Cardiac histopathology showed an increase in capillary permeability in treated animals when compared with SHAM animals. Conclusion: Noninvasive LIPUST induces significant metabolic and hemodynamic changes, including intensity-dependent bradycardia and hypotension, indicating a possible therapeutic effect for cardiac events.

The effect of gingival aging in diabetic and non-diabetic status: an experimental study / El efecto del envejecimiento gingival en el estado diabetico y no diabetico. Estudio experimental

Major gingivalperiodontal changes according to age have been observed in both diabetic and nondiabetic rats. Male Wistar rats weighing 200220 g were divided into two groups: 1) Nondiabetic (ND) and 2) Diabetic (D) by receiving an intraperitoneal (ip) dose of streptozotocin (STZ) (50 mg /kg). Animals from both groups (ND and D) were euthanized at 4, 8, 12, 17 y 25 weeks after treatment with saline solution or STZ. Glycemia values in ND rats were 5 to 6 mmol/L, while in D, glycemia increased progressively between weeks 4 and 25, with values ranging from 18.3±2.1 to 39.3±2.7 mmol/L. Oxidative stress differed significantly in gums of ND and D rats. ND: lipid peroxidation: Malondialdehyde (MDA): 8.52±1.2 to 15.5±2(nmol/mgP); superoxide dismutase (SOD): 37.1±4.2 to 21.2±1.3 (U/100mgP); D: MDA 13.1±1.6 to 22.9±2.7 (nmol/L); superoxide dismutase (SOD): 17.7±0.8 to 9.±0.2 (U/100mgP). Vascular permeability (VP) and gingival edema (E) showed significant changes between ND and D rats from 4 to 25 weeks. ND: PV: 10±0.2 to 16.1±1.3 (EB ug/g dry t); E: 0.9±0.1 to 4.1±1.3 ml; D: PV: 12±1.2 to 24.4±1.6 (EB ug/g dry t); E: 2.2±0.2 to 8.4±1.3 ml. Aging produced progressive natural changes in oxidative stress, VP and gingival E. In diabetic animals, changes in oxidative stress, VP and gingival E were observed early and were progressively more significant than for ND. According to these results, nondiabetic gingival modifications develop naturally with age, while in aging associated to diabetic disease, hyperglycemia increases progressively and early (AU)

Se han observados importantes cambios gingivoperiodontales en función de la edad tanto en ratas no diabéticas como en ratas diabéticas. Ratas machos Wistar de 200220 g de peso corporal fueron separadas en dos grupos: 1) No diabéticas(ND) ; 2) Diabéticas (D), por haber recibido una dosis intraperitoneal (ip) de estreptozotocina (STZ) (50 mg /kg). Ambos grupos de ratas (ND y D) fueron sacrificados a las 4, 8, 12, 17 y 25 semanas de edad después del tratamiento con solución salina o con STZ. En ratas ND las los valores de glucemia fueron de 5 a 6 mmol/L, en tanto que en las D las glucemias se observaron progresivamente aumentadas entre las 4 y las 25 semanas con valores entre 18.3±2.1 a 39.3±2.7 mmol/L. El estrés oxidativo mostró diferencias significativas entre las encías de animales ND respecto a los D; ND: peroxidacion lipidica: Malondihaldeido (MDA): 8.52±1.2 a 15.5±2(nmol/mgP);superoxido dismutasa (SOD):37.1±4.2 a 21.2±1.3 (U/100mgP); D : MDA 13.1±1.6 a 22.9±2.7 (nmol/L); Superoxidodismutasa :SOD 17.7±0.8 a 9.±0.2 (U/100mgP). La permeabilidad vascular(PV) y el edema(E) gingival mostraron cambios significativos entre las 4 y las 25 semanas de edad entre los animales ND respecto a los D : ND : PV : 10±0.2 a 16.1±1.3 (EB ug/g t seco); E :0.9±0.1 a 4.1±1.3 ml; D: PV :12±1.2 a 24.4±1.6 (EB ug/g t seco); E 2.2_/0.2 a 8.4± 1.3 ml. El envejecimiento produjo cambios progresivos naturales en el estrés oxidativo, PV y E gingival. En tanto que en el estado diabético los cambios del estrés oxidativo, PV y E gingival se observan temprano y fueron progresivamente más significa tivos comparados con los ND. De acuerdo a estos resultados las modificaciones gingivales no diabéticas se desarrollan naturalmente en función de la edad, en cambio en la senectud asociada con enfermedad diabética la hiperglucemia aumenta progresiva y tempranamente (AU)

Edemogenic test and hydrogen peroxide degradation rate of bleaching gels with different desensitizing agents / Teste edemogênico e taxa de degradação do peróxido de hidrogênio de géis clareadores com diferentes agentes dessensibilizantes

Objective: The at-home bleaching technique leads to the intimate contact of the bleaching gel with gingival tissues, so this study evaluated the immediate inflammatory response, through the edemogenic test, induced by at-home bleaching gels of 10% carbamide peroxide with different desensitizing agents, the quantification of hydrogen peroxide released and bleaching gels pH. Material and Methods: Forty-eight rats were divided into groups (n=12): CTRL-control group, WP-Whiteness Perfect 10% (FGM Produtos Odontológicos, Joinville, SC, Brazil), OPA-Opalescence 10% (Ultradent Products Inc., South Jordan, IT, USA), and PB-Power Bleaching (BM4, Palhoça, SC, Brazil). For the edemogenic test, all rats received an intravenous injection of Evan's Blue; after 30 min, 0.2 mL of each bleaching gels was injected into the subcutaneous tissue of the rats, and the results of the vascular permeability were assessed after 3 and 6h. The amount of HP released and pH of each product was also determined. Data were submitted to statistical test (p <0.05 ). Results: At 3h, the PB showed higher vascular permeability than the other groups. At 6h, the PB produced similar vascular permeability than WHI, and higher than OPA and CTRL groups. The OPA group had a higher vascular permeability at 6h compared to 3h; there is no difference in other groups. The PB group had higher HP concentrations than the other groups. Conclusion: In general, the PB caused a more considerable amount of inflammatory edema and higher amount of HP released. This results suggesting that these bleaching gels cause greater aggression in soft gingival tissues that eventually ends up in contact with bleaching products. (AU)

Objetivo: A técnica de clareamento domiciliar leva ao contato íntimo do gel clareador com tecidos gengivais, assim, este estudo avaliou a resposta inflamatória imediata, através do teste edemogênico, induzido por gel de clareamento caseiro à base de peróxido de carbamida a 10% com diferentes agentes dessensibilizantes, a quantificação de peróxido de hidrogênio liberado e o pH dos géis branqueadores. Material e Métodos: Quarenta e oito ratos foram divididos em 4 grupos (n = 12): grupocontrole CTRL, WP-Whiteness Perfect 10% (FGM Produtos Odontológicos, Joinville, SC, Brasil), OPA-Opalescence 10% (Ultradent Products Inc., South Jordan, IT, EUA) e PB-Power Bleaching (BM4, Palhoça, SC, Brasil). Para o teste edemogênico, todos os ratos receberam uma injeção intravenosa de Evan's Blue; após 30 min, 0,2 mL de cada gel clareador foi injetado no tecido subcutâneo dos ratos, e os resultados da permeabilidade vascular foram avaliados após 3 e 6 horas. A quantidade de HP liberada e o pH de cada produto também foram determinados. Os dados foram submetidos ao teste estatístico (P <0,05). Resultados: Às 3h, o PB apresentou maior permeabilidade vascular que os demais grupos. Às 6h, o PB produziu permeabilidade vascular semelhante ao WHI e maior que os grupos OPA e CTRL. O grupo OPA apresentou maior permeabilidade vascular às 6h em relação às 3h; Não existe essa diferença em outros grupos. O grupo PB apresentou maiores concentrações de HP que os demais grupos. Conclusão: Em geral, o PB causou maior quantidade de edema inflamatório e maior quantidade de HP liberado. Estes resultados sugerem que estes géis branqueadores causam maior agressividade nos tecidos gengivais moles que eventualmente acabam em contato com produtos de branqueamento. (AU)

How relevant are vascular endothelial growth factor and intercellular adhesion molecule in the systemic capillary leak syndrome of psoriasis?

Abstract: Psoriasis is a chronic disease, characterized by erythematous scaly lesions, presented in eight different forms: plaques, guttate, pustular, erythrodermic, inverse, nail and scalp psoriasis, and psoriatic arthritis. Its development depends on genetic factors, external stimulus and immune response alteration.1 Proinflammatory cytokines such as TNF-alpha, IL-12 and 23 may also be involved. In the worst cases, systemic complications linked to endothelial alterations may occur. A literature review was conducted for a better understanding of what roles VEGF (vascular endothelial growth factor) and ICAM-1 (intercellular adhesion molecule) have, among other cytokines, in systemic capillary leak syndrome, involved in erythrodermic and pustular psoriasis, the most unstable forms of the disease.

Reguladores de integridad endotelial como posibles predictores de la gravedad en casos de dengue / Regulators of endothelial integrity as severity predictors in dengue

Introducción. El dengue es una de las enfermedades trasmitidas por mosquitos de mayor impacto en el mundo. La evolución clínica de la enfermedad suele ser impredecible, por lo cual su adecuado manejo en las fases tempranas podría incidir en la mejoría del paciente. Objetivo. Evaluar los niveles séricos de algunos reguladores endoteliales (VEGF, sICAM-1, endoglina soluble, Ang-1 y Ang-2) como marcadores de predicción de la gravedad del dengue. Materiales y métodos. Se hizo un estudio de casos y controles anidado en una cohorte. En la fase temprana, los niveles de los reguladores endoteliales se midieron con ELISA. La relación entre las variables clínicas y los reguladores se analizó mediante regresión logística utilizando como variable de salida la gravedad del dengue. Con base en la relación entre las variables de interés y el resultado, se estableció un posible modelo predictor de la gravedad empleando la mejor área bajo la curva (ROC). Resultados. La mediana de la edad fue de 24 años. Los casos graves se asociaron con niveles séricos de Ang-2 a partir de un punto de corte mayor o igual a 1.490 pg/ml, ( Odds ratio, OR=3,1 p=0,015). Los niveles séricos de Ang-2, así como un área de 0,73 bajo la curva ROC, contribuyeron al modelo de predicción de la gravedad, conjuntamente con las variables de exantema, trastorno de conciencia y dolor abdominal, con OR de 3,2 (IC 95% 1,16-8,9; p=0,024). Conclusión. El regulador endotelial Ang-2 podría ser un predictor de la gravedad en el dengue.

Introduction: Dengue is currently among the mosquito-borne diseases of greatest global impact. The clinical course of the disease can be unpredictable, so proper handling in its early stages is critical to ensure optimal outcomes. Objective: To evaluate serum regulators of endothelial integrity (VEGF, sICAM-1, sEndoglina, Ang-1, and Ang-2) as predictive markers of dengue severity. Materials and methods: We conducted a case-control study nested in an appropriate cohort. Endothelial regulator levels were first measured by ELISA, after which analysis was performed using logistic regression of clinical and regulatory variables, with severity as an output variable. A possible severity prediction model, based on the variables of interest and output, was defined using the best area under the ROC curve. Results: The median subject age was 24 years. Severe cases were associated with Ang-2 serum levels of =1,490 ng/ml (OR=3.1; p=0.015). Serum levels of Ang-2 (=1,490 ng/ml) contributed to the severity prediction model, as did a 0.73 area under the ROC curve, together with the variables rash, impaired consciousness and abdominal pain, with an OR of 3.2 (CI 95%: 1.16 to 8.9; p=0.024). Conclusion: The endothelial regulator Ang-2 could be a predictor of severity in dengue.

Será choque séptico? Um caso raro de choque distributivo / Is this septic shock? A rare case of distributive shock

Os autores apresentam um caso raro de choque em doente sem antecedentes pessoais significativos, admitido na unidade de terapia intensiva por suspeita de choque séptico. Inicialmente, foi tratado com fluidoterapia sem melhoria, tendo sido aventada a hipótese de síndrome de hiperpermeabilidade capilar, após confirmação de hipoalbulinemia paradoxal grave, hipotensão e hemoconcentração exuberante - tríade característica da doença. Os autores discutiram o diagnóstico diferencial e ainda realizaram uma revisão do diagnóstico e do tratamento da doença.

The authors report a rare case of shock in a patient without significant clinical history, admitted to the intensive care unit for suspected septic shock. The patient was initially treated with fluid therapy without improvement. A hypothesis of systemic capillary leak syndrome was postulated following the confirmation of severe hypoalbuminemia, hypotension, and hemoconcentration - a combination of three symptoms typical of the disease. The authors discussed the differential diagnosis and also conducted a review of the diagnosis and treatment of the disease.

Biomarcadores pronósticos de gravedad del dengue / Biomarkers for the prognosis of severe dengue

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Introduction: There are very few strategies for the early detection of the patients who might develop the severe form of the illness. Objective: To evaluate the utility of serum levels of some immune response mediators as early biomarkers for the severe dengue prognosis during the early phase of the illness. Materials and methods: Using a case-control design nested in a multicenter cohort from the AEDES network (a Colombian multicenter study), we compared TNF a, ST2, TRAIL and IDO levels in samples which were obtained during the early phase of the illness. Results: ST2, TRAIL and TNF a levels were higher in severe dengue patients compared with uncomplicated patients (p<0.0001), as follows: OR=24.8, CI95%= 6.1- 98.0; OR=18.0, CI95%= 4.6-69.1; OR=NC, CI95%= NC, respectively. We did not find statistically significant differences between IDO levels in severe dengue and uncomplicated dengue (p=1.000, OR=1.0, CI95%= 0.2-6.1). Conclusions: In the early phase of the dengue infection (96 hours), ST2, TRAIL and TNF a quantifications could contribute to the prediction of complications of the illness.

Terapia gênica com fator de crescimento endotelial vascular 165 para pacientes com angina refratária: mobilização de células progenitoras endoteliais / VEGF 165 gene therapy for patients with refractory angina: mobilization of endothelial progenitor cells

FUNDAMENTO: O fator de crescimento endotelial vascular (VEGF - vascular endothelial growth factor) induz a mobilização de células progenitoras endoteliais (CPEs) com capacidade de proliferação e diferenciação em células endoteliais, contribuindo, dessa forma, para o processo angiogênico. OBJETIVO: Buscamos avaliar o comportamento de CPEs em pacientes com doença cardíaca isquêmica e angina refratária que receberam injeções intramiocardicas de 2000 µg de VEGF165 como terapia única. MÉTODOS: O estudo foi uma subanálise de um ensaio clínico. Pacientes com doença cardíaca isquêmica avançada e angina refratária foram avaliados para inclusão no estudo. Os critérios de inclusão foram: sinais e sintomas de angina e/ou insuficiência cardíaca apesar de tratamento medicamentoso máximo e área de isquemia miocárdica de, no mínimo, 5% conforme avaliado por uma tomografia computadorizada por emissão de fóton único (TCEFU). Os critérios de exclusão foram: idade > 65 anos, fração de ejeção do ventrículo esquerdo < 25% e cancer diagnosticado. Os pacientes cujos níveis de CPE foram avaliados foram incluídos. A intervenção consistiu na administração de 2000 µg de VEGF 165 de plasmídeo injetado no miocárdio isquêmico. A frequência de células CD34+/KDR+ foi analisada por citometria de fluxo antes e 3, 9, e 27 dias após a intervenção. RESULTADOS: Um total de 9 pacientes foram incluídos, 8 homens, média de idade de 59,4 anos, fração de ejeção ventricular esquerda de 59,3%, e classe de angina predominante III. Observou-se um aumento significativo dos níveis de CPEs no terceiro dia após a intervenção. Todavia, 9 e 27 dias após a intervenção, os níveis de CPEs foram similares aos basais. CONCLUSÃO: Identificamos uma mobilização transitória de CPE, com pico no terceiro dia após a intervenção com VEGF 165 em pacientes com angina refratária. Todavia, os níveis de CPEs apresentaram-se semelhantes aos basais 9 e 27 dias após a intervenção.

BACKGROUND: Vascular endothelial growth factor (VEGF) induces mobilization of endothelial progenitor cells (EPCs) with the capacity for proliferation and differentiation into mature endothelial cells, thus contributing to the angiogenic process. OBJECTIVE: We sought to assess the behavior of EPCs in patients with ischemic heart disease and refractory angina who received an intramyocardial injections of 2000 µg of VEGF 165 as the sole therapy. METHODS: The study was a subanalysis of a clinical trial. Patients with advanced ischemic heart disease and refractory angina were assessed for eligibility. Inclusion criteria were as follows: signs and symptoms of angina and/or heart failure despite maximum medical treatment and a myocardial ischemic area of at least 5% as assessed by single-photon emission computed tomography (SPECT). Exclusion criteria were as follows: age > 65 years, left ventricular ejection fraction < 25%, and a diagnosis of cancer. Patients whose EPC levels were assessed were included. The intervention was 2000 µg of VEGF 165 plasmid injected into the ischemic myocardium. The frequency of CD34+/KDR+ cells was analyzed by flow cytometry before and 3, 9, and 27 days after the intervention. RESULTS: A total of 9 patients were included, 8 males, mean age 59.4 years, mean left ventricular ejection fraction of 59.3% and predominant class III angina. The number of EPCs on day 3 was significantly higher than that at baseline (p = 0.03); however, that on days 9 and 27 was comparable to that at baseline. CONCLUSION: We identified a transient mobilization of EPCs, which peaked on the 3th day after VEGF 165 gene therapy in patients with refractory angina and returned to near baseline levels on days 9 and 27.

Síndrome de extravasamento capilar sistêmico / Systemic capillary leak syndrome

A síndrome de extravasamento capilar sistêmico é rara e causada por aumento da permeabilidade capilar. Várias etiologias estão envolvidas. No nosso serviço de Dermatologia, a principal é a psoríase instável. Diversos tratamentos são usados e muitos ainda estão em estudo. Nosso objetivo foi apresentar esta situação clínica potencialmente fatal que ocorre em nossa especialidade.

The systemic capillary leak syndrome is rare and caused by increased capillary permeability. Several etiologies are involved. In our Department of Dermatology the main one is unstable psoriasis. Several treatments are used and many are still under study. Our objective was to present this potentially fatal medical condition that occurs in our specialty.

Alternativas de prevenção da síndrome de hiperestimulação ovariana / Ovarian hyperstimulation syndrome prevention alternatives

A Síndrome de Hiperestimulação Ovariana (SHEO) é uma complicação iatrogênica e potencialmente fatal, resultante da estimulação ovariana excessiva em resposta às gonadotrofinas exógenas. As principais características desta síndrome são: aumento da permeabilidade capilar que leva a uma grande troca de fluído do espaço intravascular para o terceiro espaço; e crescimento excessivo do volume ovariano. Várias estratégias para a prevenção desta síndrome foram propostas: infusão de albumina, coasting, anti-inflamatórios, bloqueio do sistema renina-angiotensina, agonistas dopaminérgicos, redução da dose de gonadotrofina coriônica humana (hCG), substituição da hCG e maturação in vitro de oócitos. Nesta revisão, as evidências atuais que suportam tais estratégias, de maneira a permitir que o médico escolha a melhor alternativa, foram avaliadas

Ovarian Hyperstimulation Syndrome (OHSS) is an iatrogenic and potentially life-threatening complication, which results from an excessive ovarian stimulation to exogenous gonadotropins. The main characteristics of this syndrome are: increased capillary permeability with a massive shift of fluid from the intra-vascular compartment to the third space; and an excessive increase of ovarian volumes. Several strategies for the prevention of this syndrome were proposed: albumin infusion, coasting, anti-inflammatory drugs, renin-angiotensin system blockage, dopaminergic agonists, human chorionic gonadotrophin (hCG) dose reduction, hCG substitution and in vitro maturation of oocytes. In this review, the current evidences to support these strategies were evaluated, in order to permit that the physician chooses the best alternative

The contribution of arterial versus venous vascular permeability in peritoneal fluid formation

OBJETIVO: o acúmulo de líquido peritoneal é um achado comum em muitas crianças com distúrbios abdominais e sua geração é secundária ao aumento da permeabilidade vascular. A contribuição da circulação arterial versus venosa para a formação de edema e acúmulo de líquido peritoneal é mal compreendida. Estudos realizados in vivo mais de duas décadas atrás, sugeriram que a vênulas são mais importantes que os vasos arteriais no processo de formação de edema. O objetivo deste trabalho é analisar os efeitos das mudanças na pressão intravascular e a inflamação mediada pela bradicinina na permeabilidade venosa e vascular mesentérica de ratos. MÉTODO: artérias mesentéricas (MA) e veias (MV) foram montadas em cânulas de vidro, por via intravenosa preenchida com dextran fluorescentes e incremental pressurizado acima de seus valores fisiológicos in vivo. Permeabilidade vascular para dextrana foi determinada a 100, 200 e 300 por cento de pressões fisiológicas. RESULTADOS: a permeabilidade vascular estava presente em todas as medidas para ambos os vasos e sua magnitude diretamente proporcional à pressão intravascular. A bradicinina (10-5 M) aumentou significativamente a permeabilidade da MV, mas não no MA. CONCLUSÃO: o acúmulo de líquido abdominal relacionado à doença inflamatória intestinal é mais provável de ser secundária a venosa, em oposição à fuga vascular arterial

Aspectos celulares da cicatrização: [revisão] / Cellular aspects of wound healing: [review]

O processo cicatricial compreende uma sequência de eventos moleculares e celulares que interagem para que ocorra a restauração do tecido lesado. Desde o extravasamento de plasma, com a coagulação e agregação plaquetária até a reepitelização e remodelagem do tecido lesado o organismo age tentando restaurar a funcionalidade tecidual. Assim, este trabalho abrange os diversos aspectos celulares envolvidos no processo cicatricial, bem como os principais medicamentos utilizados no tratamento de patologias relacionadas às deficiências na cicatrização. São abordados também, os aspectos econômicos referentes, sobretudo, às feridas crônicas de pés diabéticos.

Wound healing is a dynamic interactive process that involves a sequence of molecular and cellular events. Recent advances in cellular and molecular biology have greatly expanded our understanding of the biological process involved in wound repair and tissue regeneration. From plasma extravasation, with coagulation and platelet aggregation, to reepithelialization and remodeling of injured tissue, the organism acts by trying to restore functionality tissue. Thus, the present study encompasses several cellular aspects involved in the wound healing process, as well as the main drugs used in treating the pathology related to wound healing complications. Economic aspects are also addressed, mainly related to chronic wounds of diabetic feet.

Alveolus-capillary permeability on both normal and HIV seroreactive individuals

The aim of this study was to evaluate the alveolus-capillary permeability by the lung clearance rate of 99mTc-DTPA(Technetium99m-diethylene triamine penta-acetate), (LCR-DTPA), both in normal and in asymptomatic HIV seroreactive patients. Thirty individuals were studied, 21 seronegative normal volunteers and 9 HIV seroreactive patients presenting normal chest radiography and no respiratory infection symptoms. LCR-DTPA was determined by inhaling 99mTc-DTPA and obtaining images in a gamma camera. The 99mTc-DTPA clearance rate in normal individuals was 0.99±0.15 percent.min-1 and in patients 2.31±1.25 percent.min-1. There was a significant statistical difference between the two groups (p< 0.05). Two patients who presented LCR-DTPA higher than 4.3 percent.min-1 presented pneumocystis pneumonia one month later. Seroreactive AIDS patients, previously asymptomatic that presented pneumonia later showed higher LCR-DTPA than the seroreactive who did not develop the illness. These results suggested that LCR-DTPA could be a predictive method for the clinical development of pneumocystis pneumonia in asymptomatic HIV seroreactive patients.

A integridade funcional da barreira alvéolo-capilar pode ser alterada por diversas condições patológicas e por outros fatores como a irritação do epitélio alveolar, provocada pelo fumo etc, levando a um aumento da permeabilidade alvéolo-capilar. O objetivo deste trabalho foi verificar a permeabilidade do epitélio pulmonar através da determinação da taxa de depuração pulmonar do aerossol de 99mTc-DTPA (LCR-DTPA) em indivíduos normais e em pacientes assintomáticos HIV sororreativos. Foram estudados 30 indivíduos, sendo 21 voluntários normais e 9 HIV sororreativos sem sintomas de infecção oportunista, com radiografias de tórax normais ou sem sinais sugestivos de infecção pulmonar. A LCR-DTPA foi determinada após inalação de 99mTc-DTPA sob a forma de aerossóis e contagem externa da radiação, em função do tempo, em gama câmara. A LCR-DTPA dos controles foi de 0.99±0.15 por cento.min-1 e nos pacientes sororreativos,de 2.31±1.15 por cento.min-1 houve diferença significativa entre os dois grupos (p< 0.05). Dois pacientes tiveram LCR-DTPA acima de 4,3 por cento.min-1, estes desenvolveram um mês após o exame. Observou-se que os pacientes sororreativos por Imunodeficiência Adquirida (SIDA), sem sintomas específicos para pneumocistose que posteriormente desenvolveram a doença, a LCR-DTPA foi significativamente maior que a dos outros HIV pneumocistose clínica sororreativos que não desenvolveram a doença (p<0.01). Estes resultados sugerem que a LCR-DTPA pode ser um método preditivo do desenvolvimento clínico da pneumocistose, não invasivo, de fácil realização e cômodo, para o paciente HIV sororreativo assintomático.

Estudo experimental da transmissão da pulsatilidade da endoprótese à parede do aneurisma da aorta após correção endoluminal / Pulsatility transmission from endograft to aortic aneurysm wall after endovascular repair: an experimental study

Objetivo: Medir a pulsatilidade da parede do aneurisma de aorta humano antes e depois de sua correção endoluminal. Método: Cinco aneurismas foram submetidos à perfusão pulsátil antes e depois do implante de uma endoprótese. Resultado: o nível da coluna de água oscilou durante a pulsação com variações de 17, 16, 13, 7 e 25 cm antes da colocação da endoprótese. Depois da prótese, a oscilação diminuiu em todos os casos para 13, 12, 9, 3,5 e 23 cm, respectivamente. Conclusão: A pulsação da endoprótese é transmitida à parede do aneurisma.

Objective: To measure the pulsatility of human aortic aneurysms before and after exclusion with endograft. Method: Five aneurysms were submitted to pulsatile perfusion before and after implantation of a bifurcated endograft. Result: The level of the water column oscillated during pulsation, in each case, with an amplitude of 17, 16, 13, 7 and 25 cm before the endograft insertion. After that, the amplitudes dropped to, respectively 13, 12, 9, 3.5 and 23 cm.Conclusion: Pulsation of an endograft is transmitted to the aneurysm wall even in the absence of endoleak.