Validity and reproducibility of retinal arteriole and venule diameter measurements: ELSA-Brasil study. A cross-sectional study

ABSTRACT BACKGROUND: Investigation of alterations to retinal microvasculature may contribute towards understanding the role of such changes in the pathophysiology of several chronic non-communicable diseases. The objective here was to evaluate the validity and reproducibility of retinal arteriole and venule diameter measurements made by Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) graders. DESIGN AND SETTING: Cross-sectional study at six teaching and research institutions. METHODS: To evaluate validity, each of 25 retinal images from the University of Wisconsin (gold standard) was measured by five ELSA-Brasil graders. To evaluate reproducibility, 105 images across the spectrum of vessel diameters were selected from 12,257 retinal images that had been obtained between 2010 and 2012, and each image was reexamined by the same grader and by an independent grader. All measurements were made using the Interactive Vessel Analysis (IVAN) software. Bland-Altman plots, paired t tests and intraclass correlation coefficients (ICCs) were analyzed. RESULTS: Mean differences between ELSA-Brasil and gold-standard readings were 0.16 µm (95% CI -0.17-0.50; P = 0.31) for central retinal artery equivalent (CRAE), -0.21 µm (95% CI -0.56-0.14; P = 0.22) for central retinal vein equivalent (CRVE) and 0.0005 (95% CI -0.008-0.009; P = 0.55) for arteriole/venule ratio (AVR). Intragrader ICCs were 0.77 (95% CI 0.67-0.86) for CRAE, 0.90 (95% CI 0.780.96) for CRVE and 0.70 (0.55-0.83) for AVR. Intergrader ICCs were 0.75 (95% CI 0.64-0.85) for CRAE, 0.90 (95% CI 0.79-0.96) for CRVE and 0.68 (95% CI 0.55-0.82) for AVR. CONCLUSIONS: Retinal microvascular diameter measurements are valid and present moderate to high intra and intergrader reproducibility in ELSA-Brasil.

Exercise Training Attenuates Sympathetic Activity and Improves Morphometry of Splenic Arterioles in Spontaneously Hipertensive Rats / Treinamento Físico Atenua a Atividade Simpática e Melhora a Morfometria das Arteríolas Esplênicas em Ratos Espontaneamente Hipertensos

Abstract Background: Alterations in the structure of resistance vessels contribute to elevated systemic vascular resistance in hypertension and are linked to sympathetic hyperactivity and related lesions in target organs. Objective: To assess the effects of exercise training on hemodynamic and autonomic parameters, as well as splenic arteriolar damages in male Wistar Kyoto (WKY) and Spontaneously Hypertensive Rats (SHR). Methods: Normotensive sedentary (WKYS) and trained (WKYT) rats, and hypertensive sedentary (SHRS) and trained (SHRT) rats were included in this study. After 9 weeks of experimental protocol (swimming training or sedentary control), arterial pressure (AP) and heart rate (HR) were recorded in freely moving rats. We assessed the autonomic control of the heart by sympathetic and vagal autonomic blockade. Morphometric analyses of arterioles were performed in spleen tissues. The statistical significance level was set at p < 0.05. Results: Resting bradycardia was observed in both trained groups (WKYT: 328.0 ± 7.3 bpm; SHRT: 337.0 ± 5.2 bpm) compared with their respective sedentary groups (WKYS: 353.2 ± 8.5 bpm; SHRS: 412.1 ± 10.4 bpm; p < 0.001). Exercise training attenuated mean AP only in SHRT (125.9 ± 6.2 mmHg) vs. SHRS (182.5 ± 4.2 mmHg, p < 0.001). The WKYT showed a higher vagal effect (∆HR: 79.0 ± 2.3 bpm) compared with WKYS (∆HR: 67.4 ± 1.7 bpm; p < 0.05). Chronic exercise decreased sympathetic effects on SHRT (∆HR: -62.8 ± 2.8 bpm) in comparison with SHRS (∆HR: -99.8 ± 9.2 bpm; p = 0.005). The wall thickness of splenic arterioles in SHR was reduced by training (332.1 ± 16.0 µm2 in SHRT vs. 502.7 ± 36.3 µm2 in SHRS; p < 0.05). Conclusions: Exercise training attenuates sympathetic activity and AP in SHR, which may be contributing to the morphological improvement of the splenic arterioles.

Resumo Fundamento: Alterações na estrutura dos vasos de resistência contribuem para elevar a resistência vascular sistêmica na hipertensão, estando ligadas à hiperatividade simpática e lesões em órgãos-alvo. Objetivo: Avaliar os efeitos do treinamento físico nos parâmetros hemodinâmicos e autônomos, assim como as lesões arteriolares esplênica em ratos machos Wistar Kyoto (WKY) e espontaneamente hipertensos (SHR). Métodos: Ratos normotensos sedentários (WKYS) e treinados (WKYT), e ratos hipertensos sedentários (SHRS) e treinados (SHRT) foram incluídos neste estudo. Após nove semanas de aplicação do protocolo experimental (treinamento de natação ou controle sedentário), registraram-se a pressão arterial (PA) e a frequência cardíaca (FC) dos ratos em movimento livre. Avaliamos o controle autônomo do coração através de bloqueio autônomo simpático e vagal. Análises morfométricas das arteríolas esplênicas foram realizadas. Adotou-se o nível de significado estatístico de p < 0,05. Resultados: Observou-se bradicardia de repouso nos dois grupos treinados (WKYT: 328,0 ± 7,3 bpm; SHRT: 337,0 ± 5,2 bpm) em comparação aos seus respectivos grupos sedentários (WKYS: 353,2 ± 8,5 bpm; SHRS: 412,1 ± 10,4 bpm; p < 0,001). O treinamento físico atenuou a PA média apenas no grupo SHRT (125,9 ± 6,2 mmHg vs. 182,5 ± 4,2 mmHg no SHRS; p < 0,001). O grupo WKYT mostrou maior efeito vagal (∆FC: 79,0 ± 2,3 bpm) em comparação ao grupo WKYS (∆FC: 67,4 ± 1,7 bpm; p < 0,05). Exercício crônico diminuiu os efeitos simpáticos em SHRT (∆FC: -62.8 ± 2.8 bpm) em comparação a SHRS (∆FC: -99,8 ± 9,2 bpm; p = 0,005). A espessura da parede das arteríolas esplênicas nos SHR foi reduzida pelo treinamento (332,1 ± 16,0 µm2 nos SHRT vs. 502,7 ± 36,3 µm2 nos SHRS; p < 0,05). Conclusões: O treinamento físico atenua a atividade simpática e a PA em SHR, o que pode contribuir para melhorar a morfologia das arteríolas esplênicas.

Ventilation-induced changes correlate to pulmonary vascular response and VEGF, VEGFR-1/2, and eNOS expression in the rat model of postnatal hypoxia

Neonatal asphyxia occurs due to reduction in oxygen supply to vital organs in the newborn. Rapid restoration of oxygen to the lungs after a long period of asphyxia can cause lung injury and decline of respiratory function, which result from the activity of molecules that induce vascular changes in the lung such as nitric oxide (NO) and vascular endothelial growth factors (VEGF). In this study, we evaluated the pulmonary and vascular morphometry of rats submitted to the model of neonatal asphyxia and mechanical ventilation, their expression of pulmonary VEGF, VEGF receptors (VEGFR-1/VEGFR-2), and endothelial NO synthase (eNOS). Neonate Sprague-Dawley rats (CEUA #043/2011) were divided into four groups (n=8 each): control (C), control submitted to ventilation (CV), hypoxia (H), and hypoxia submitted to ventilation (HV). The fetuses were harvested at 21.5 days of gestation. The morphometric variables measured were body weight (BW), total lung weight (TLW), left lung weight (LLW), and TLW/BW ratio. Pulmonary vascular measurements, VEGFR-1, VEGFR-2, VEGF, and eNOS immunohistochemistry were performed. The morphometric analysis showed decreased TLW and TLW/BW ratio in HV compared to C and H (P<0.005). Immunohistochemistry showed increased VEGFR-2/VEGF and decreased VEGFR-1 expression in H (P<0.05) and lower eNOS expression in H and HV. Median wall thickness was increased in H, and the expression of VEGFR-1, VEGFR-2, VEGF, and eNOS was altered, especially in neonates undergoing H and HV. These data suggested the occurrence of arteriolar wall changes mediated by NO and VEGF signaling in neonatal hypoxia.

Papel da Apoptose em Obstetrícia / Role of Apoptosis in Obstetrics

Apoptose, ou morte celular programada, é um mecanismo fisiológico universal entre mamíferos que regula o equilíbrio entre proliferação e morte celular a fim de manter a homeostase tecidual. Nesse processo, a apoptose poderá ser iniciada intrinsicamente por via mitocondrial ou, extrinsecamente, mediada por sinalização via receptor de morte ou em resposta a elementos exógenos como citocinas e processos não excludentes, complementares e com ativação cruzada. As moléculas envolvidas no controle das vias de ativação da apoptose são as proteínas anti, pró-apoptóticas e caspases. Esse fenômeno biológico, além de desempenhar um papel importante no controle de diversos processos vitais, está associado a inúmeras complicações da gravidez como toxemia, crescimento intrauterino restrito, parto pré-termo, diabetes gestacional, abortamento, gravidez ectópica e a transformação maligna da mola hidatiforme. No denominador comum dessas doenças está o desconhecimento de sua etiopatogenia e o desenvolvimento/funcionamento placentário anormal. Compreender todas essas alterações deverá interessar não apenas ao pesquisador dessas moléstias, mas também aos clínicos que tratam essas doenças no intuito de se incorporar novas tecnologias na rotina médica e na melhoria das perspectivas prognósticas e terapêuticas dentro da obstetrícia.(AU)

Apoptosis, or programmed cell death, is a universal physiological mechanism in mammals, which regulates the balance between cell proliferation and death in order to maintain tissue homeostasis. In this process, apoptosis can be initiated intrinsically or extrinsically by mitochondrial pathway, mediated by death receptor signaling or in response to exogenous factors such as cytokines and processes not mutually exclusive, complementary and cross-activation. The molecules involved in the control of apoptosis activation pathways are anti and pro-apoptotic proteins as well as caspases. This biological phenomenon, besides play an important role in the control of many vital processes, is associated with many complications of pregnancy such as toxemia, intrauterine growth, preterm birth, gestational diabetes, miscarriage, ectopic pregnancy and malignant in transformation hydatiform mole. The common denominator of these diseases is the lack of knowledge about its pathogenesis and development/abnormal placental function. Understand all these changes should interest not only to the researchers, but also for clinicians who treat these diseases in order to incorporate new technologies in the medical routine and in improving prognostic and therapeutic perspectives in obstetrics.(AU)

Lesão de Dieulafoy do fundo gástrico / Dieulafoys lesion of the gastric fundus

Hemorragia digestiva alta (HDA) é uma emergência clínica exteriorizada através de melena, hematêmese, além de alterações hemodinâmicas decorrentes de perda volêmica. Existem vários diagnósticos etiológicos causadores de hemorragias digestivas altas; dentre eles, uma causa rara é lesão de Dieulafoy, sendo relacionada acerca de 2% dos casos de HDA. Neste relato, descreveremos um caso de lesão de Dieulafoy, evidenciando a relevância desta lesão como um importante diagnóstico diferencial nas causas de hemorragia digestiva alta. O procedimento diagnóstico e o manejo atual são fundamentados pela endoscopia digestiva alta. A hemostasia endoscópica é realizada, utilizando técnicas como eletrocoagulação, injeções com adrenalina e hemoclips.

Upper gastrointestinal bleeding (UGBI) is a clinical emergency externalized through melena, hematemesis and hemodynamic changes due to volume loss. There are a lot of etiological diagnosis of gastroduodenal hemorrhages, including Dieulafoy which is a rare cause related about 2% of the UGBI cases. In this report we describe a case of Dieulafoy lesion highlighting the importance of this lesion as a rare and important differential diagnosis in cases of upper gastrointestinal bleeding. The current diagnostic and management is justified by endoscopy. Endoscopic hemostasis is performed using techniques such as electrocoagulation, injections of adrenaline and hemo-clips.

The histological analysis of the glenohumeral "critical zone" / Análisis histológico de la "zona crítica" glenohumeral

The arterial integrity of the "critical zone" of the rotator cuff has led to much uncertainty regarding rotator cuff tendinopathy. As the region of the supraspinatus tendon is the most common area affected by impingement, its central aspect is situated approximately 10 mm from the insertion at the greater humeral tubercle. Although many studies have investigated the vascularity of the "critical zone", there still appears to be lack of consensus regarding its extent. Through the employment of gross dissection and standard histology analysis of twenty-five adult bilateral cadaveric scapulo-humeral regions (n = 50), this study aimed to quantify the degree of vascularity, or lack thereof, within the "critical zone" by evaluating its relative morphometric features. The demographic representation of the sample was also considered. Results: i) Mean diameter of arteriole lumen: 91.6±75.2 µm; ii) Mean diameter of entire arteriole: 119.8±87.1 µm; iii) Mean arteriole wall thickness: 15.1±9.5 µm; iv) Mean area occupied by an arteriole: 20644.4±3358.0 µm2; v) Mean number of arterioles within "critical zone": 14.6±8.7. All tissue samples displayed a scarce distribution of arterioles along the musculo-tendinous junction relative to the "critical zone". A directly proportional relationship between the morphometric parameters was indicated by positive strong correlations and accompanying statistically significant P values. As 66 % of the number of arterioles within the "critical zone" were distributed between the minimum value and the upper quartile, it was postulated to be hypovascular, therefore confirming the findings of previous studies.

La integridad arterial de la "zona crítica" del manguito rotador ha dado lugar a una gran incertidumbre con respecto a la tendinitis del mismo. A medida que la región del tendón del músculo supraespinoso sea el área más común afectada por el impacto, su aspecto central estará situado aproximadamente a 10 mm desde la inserción en el tubérculo mayor del húmero. Aunque muchos estudios han investigado la vascularización de la "zona crítica", aún parece existir falta de consenso en cuanto a su extensión. A través de la disección macroscópica y análisis de la histología normal de ambas regiones escápulo-humerales, se realizó en 25 cadáveres adultos (n = 50), este estudio que tuvo como objetivo cuantificar el grado de vascularización, o su ausencia, dentro de la "zona crítica" mediante la evaluación de su características morfométricas. También se consideró la representación demográfica de la muestra. Resultados: i) La media de diámetro de lumen de las arteriolas: 91,6 ± 75.2 µm; ii) El diámetro medio de la totalidad de las arteriolas: 119,8 ± 87.1 µm; iii) la media del espesor de la pared de las arteriolas: 15,1 ± 9.5µm; iv) La media de la zona ocupada por una arteriola: 20.644,4 ± 3358.0 µm2; v) La media de las arteriolas dentro de la "zona crítica": 14,6 ± 8,7. Todas las muestras de tejidos tenían una escasa distribución de las arteriolas a lo largo de la unión músculo-tendinosa con relación a la "zona crítica". Una relación directamente proporcional entre los parámetros morfométricos indica fuertes correlaciones positivas y junto a valores de P estadísticamente significativos. Como el 66 % de las arteriolas dentro de la "zona crítica" se distribuyeron entre el valor de cuartil mínimo y superior, se postuló como hipovascular, por lo tanto confirma los resultados de estudios anteriores.

Contexto sociodemográfico de los homicidios en México D.F.: un análisis espacial / Sociodemographic context of homicide in Mexico City: a spatial analysis

OBJETIVO:Investigar el patrón de distribución espacial de la tasa de homicidios y su relación con las características sociodemográficas en las delegaciones de Benito Juárez, Coyoacán y Cuauhtémoc de la Ciudad de México en el año 2010. MÉTODOS: Estudio inferencial de corte transversal que usa métodos de análisis espacial para estudiar la asociación espacial de la tasa de homicidios y las características demográficas. La asociación espacial fue determinada a través del cociente de localización, análisis de regresión múltiple y el uso de la regresión geográficamente ponderada. RESULTADOS: Los homicidios muestran un patrón de localización heterogéneo con altas tasas en zonas con uso del suelo no residencial, con baja densidad de población y baja marginación. CONCLUSIONES: El uso de herramientas de análisis espacial son instrumentos poderosos para el diseño de políticas de seguridad pública preventiva y recreativa que busquen reducir la mortalidad por causas externas como homicidios.

OBJECTIVE:Investigate the spatial distribution pattern of the homicide rate and its relation to sociodemographic features in the Benito Juárez, Coyoacán, and Cuauhtémoc districts of Mexico City in 2010. METHODS: Inferential cross-sectional study that uses spatial analysis methods to study the spatial association of the homicide rate and demographic features. Spatial association was determined through the location quotient, multiple regression analysis, and the use of geographically weighted regression. RESULTS: Homicides show a heterogeneous location pattern with high rates in areas with non-residential land use, low population density, and low marginalization. CONCLUSIONS: Spatial analysis tools are powerful instruments for the design of prevention- and recreation-focused public safety policies that aim to reduce mortality from external causes such as homicides.

Effect of gender on training-induced vascular remodeling in SHR

There is accumulating evidence that physical inactivity, associated with the modern sedentary lifestyle, is a major determinant of hypertension. It represents the most important modifiable risk factor for cardiovascular diseases, which are the leading cause of morbidity and mortality for both men and women. In addition to involving sympathetic overactivity that alters hemodynamic parameters, hypertension is accompanied by several abnormalities in the skeletal muscle circulation including vessel rarefaction and increased arteriole wall-to-lumen ratio, which contribute to increased total peripheral resistance. Low-intensity aerobic training is a promising tool for the prevention, treatment and control of high blood pressure, but its efficacy may differ between men and women and between male and female animals. This review focuses on peripheral training-induced adaptations that contribute to a blood pressure-lowering effect, with special attention to differential responses in male and female spontaneously hypertensive rats (SHR). Heart, diaphragm and skeletal muscle arterioles (but not kidney arterioles) undergo eutrophic outward remodeling in trained male SHR, which contributed to a reduction of peripheral resistance and to a pressure fall. In contrast, trained female SHR showed no change in arteriole wall-to-lumen ratio and no pressure fall. On the other hand, training-induced adaptive changes in capillaries and venules (increased density) were similar in male and female SHR, supporting a similar hyperemic response to exercise.

Short-term exposure of mice to cigarette smoke and/or residual oil fly ash produces proximal airspace enlargements and airway epithelium remodeling

Chronic obstructive pulmonary disease (COPD) is associated with inflammatory cell reactions, tissue destruction and lung remodeling. Many signaling pathways for these phenomena are still to be identified. We developed a mouse model of COPD to evaluate some pathophysiological mechanisms acting during the initial stage of the disease. Forty-seven 6- to 8-week-old female C57/BL6 mice (approximately 22 g) were exposed for 2 months to cigarette smoke and/or residual oil fly ash (ROFA), a concentrate of air pollution. We measured lung mechanics, airspace enlargement, airway wall thickness, epithelial cell profile, elastic and collagen fiber deposition, and by immunohistochemistry transforming growth factor-β1 (TGF-β1), macrophage elastase (MMP12), neutrophils and macrophages. We observed regional airspace enlargements near terminal bronchioles associated with the exposure to smoke or ROFA. There were also increases in airway resistance and thickening of airway walls in animals exposed to smoke. In the epithelium, we noted a decrease in the ciliated cell area of animals exposed to smoke and an increase in the total cell area associated with exposure to both smoke and ROFA. There was also an increase in the expression of TGF-β1 both in the airways and parenchyma of animals exposed to smoke. However, we could not detect inflammatory cell recruitment, increases in MMP12 or elastic and collagen fiber deposition. After 2 months of exposure to cigarette smoke and/or ROFA, mice developed regional airspace enlargements and airway epithelium remodeling, although no inflammation or increases in fiber deposition were detected. Some of these phenomena may have been mediated by TGF-β1.

Vimentin and laminin are altered on cheek pouch microvessels of streptozotocin-induced diabetic hamsters

OBJECTIVE: Normal endothelial cells respond to shear stress by elongating and aligning in the direction of fluid flow. Hyperglycemia impairs this response and contributes to microvascular complications, which result in deleterious effects to the endothelium. This work aimed to evaluate cheek pouch microvessel morphological characteristics, reactivity, permeability, and expression of cytoskeleton and extracellular matrix components in hamsters after the induction of diabetes with streptozotocin. METHODS: Syrian golden hamsters (90-130 g) were injected with streptozotocin (50 mg/kg, i.p.) or vehicle either 6 (the diabetes mellitus 6 group) or 15 (the diabetes mellitus 15 group) days before the experiment. Vascular dimensions and density per area of vessels were determined by morphometric and stereological measurements. Changes in blood flow were measured in response to acetylcholine, and plasma extravasation was measured by the number of leakage sites. Actin, talin, α-smooth muscle actin, vimentin, type IV collagen, and laminin were detected by immunohistochemistry and assessed through a semiquantitative scoring system. RESULTS: There were no major alterations in the lumen, wall diameters, or densities of the examined vessels. Likewise, vascular reactivity and permeability were not altered by diabetes. The arterioles demonstrated increased immunoreactivity to vimentin and laminin in the diabetes mellitus 6 and diabetes mellitus 15 groups. DISCUSSION: Antibodies against laminin and vimentin inhibit branching morphogenesis in vitro. Therefore, laminin and vimentin participating in the structure of the focal adhesion may play a role in angiogenesis. CONCLUSIONS: Our results indicated the existence of changes related to cell-matrix interactions, which may contribute to the pathological remodeling that was already underway one week after induction of experimental diabetes.

Sildenafil preserves diastolic relaxation after reduction by L-NAME and increases phosphodiesterase-5 in the intercalated discs of cardiac myocytes and arterioles

OBJECTIVES: We investigated the influence of sildenafil on cardiac contractility and diastolic relaxation and examined the distribution of phosphodiesterase-5 in the hearts of hypertensive rats that were treated with by NG-nitro-L-arginine methyl ester (L-NAME). METHODS: Male Wistar rats were treated with L-NAME and/or sildenafil for eight weeks. The Langendorff method was used to examine the effects of sildenafil on cardiac contractility and diastolic relaxation. The presence and location of phosphodiesterase-5 and phosphodiesterase-3 were assessed by immunohistochemistry, and cGMP plasma levels were measured by ELISA. RESULTS: In isolated hearts, sildenafil prevented the reduction of diastolic relaxation (dP/dt) that was induced by L-NAME. In addition, phosphodiesterase-5 immunoreactivity was localized in the intercalated discs between the myocardial cells. The staining intensity was reduced by L-NAME, and sildenafil treatment abolished this reduction. Consistent with these results, the plasma levels of cGMP were decreased in the L-NAME-treated rats but not in rats that were treated with L-NAME + sildenafil. CONCLUSION: The sildenafil-induced attenuation of the deleterious hemodynamic and cardiac morphological effects of L-NAME in cardiac myocytes is mediated (at least in part) by the inhibition of phosphodiesterase-5.

A microcirculação da bolsa da bochecha do hamster sob a influência do diabetes mellitus experimental induzido por estreptozotocina: aspectos morfofuncionais / Microcirculation of hamster cheek pouch under the influence of experimental Diabetes Mellitus induced by streptozotocin: morpho-functional aspects

O Diabetes Mellitus é uma doença metabólica crônica com múltiplos fatores etiológicos (genético, viral e imunológico) que condiciona deficiência absoluta ou relativa de insulina, causando persistência de níveis elevados de glicose no sangue. Atualmente, o Diabetes Mellitus é considerado um importante problema de saúde devido a sua prevalência e alta morbimortalidade. Sua importância clínica resulta essencialmente de suas graves complicações, especialmente as microvasculares. A hiperglicemia crônica ou intermitente tem sido identificada como o fator indutor de lesão endotelial, sendo este, o agente desencadeante das complicações microvasculares. As células endoteliais, por serem influenciadas pela força hemodinâmica local, respondem com a transdução de sinais (mecanotrans dução), as quais podem ser responsáveis pelo início de processos patológicos na parede dos vasos. Desta forma, o objetivo deste estudo foi analisar a microcirculação da bolsa da bochecha do hamster sob a influência do Diabetes Mellitus tipo 1 experimental induzido por estreptozotocina, avaliando seus aspectos morfofuncionais aos 6 e 15 dias de evolução da doença. As características morfológicas de arteríolas e vênulas foram estimadas por medidas do diâmetro do lúmen e da espessura da parede; pela densidade de volume e de área destes vasos na bolsa da bochecha; pela análise imunohistoquímica da expressão de actina, talina, alfa-actina de músculo liso, vimentina, laminina e colágeno IV através da microscopia de luz com a utilização de um sistema semiquantitativo baseado em uma escala de intensidade de imunomarcação; e por microscopia eletrônica de transmissão. Também foi avaliado o relaxamento dependente do endotélio, medido pela variação do diâmetro do lúmen antes e após a aplicação de acetilcolina e a permeabilidade de vênulas pós-capilares à histamina, determinada pelo número de pontos de extravasamento plasmático. Nossos resultados mostraram que arteríolas e vênulas...

Diabetes Mellitus is a chronic metabolic disease with multiple etiologic factors (genetic, viral and immunological) that results in absolute or relative insulin deficiency, causing persistent elevated blood glucose levels. Nowadays, Diabetes Mellitus is considered as an important health concern due to its increasing prevalence and high morbimortality. Its clinical importance comes from the complications, especially harm inductor factor, being this the first outcome of microvascular complications. Endothelial cells, under local hemodynamic strength, produce signal transduction (mechanotransduction), which can be responsible for the beginning of patholgical events in vessels wall. In this regard, the objective of this study was to analyze hamster cheek pouch microcirculation under the influence of type 1 diabetes mellitus induced by streptozotocin, evaluationg its morpho-functional aspects at 6 and 15 days of diseases evolution. Morphological characteristics of arterioles and venules were estimated by the measurement of lumen diameter and wall thickness; the volume density and area of these vessels from cheek pouch; immunohistochemistry of the expression of actin, talin, smooth muscle alpha-actin, vimentin, laminin and type IV collagen through light microscopy with the utilization of a semi-quantitative score system based on the intensity of the immunostaining; and transmission electron microscopy. It was also evaluated the endothelium dependent relaxation, measured by the variation of lumen diameter before and after acetylcholine administration and post-capillary venules permeability to histamine, determined by number of points of plasma extravasation. Our results reveal that arterioles and venules do not show differences between the groups concerning wall thickness, luminal diameter, density per area and volume density. Vascular permeability, after 2 minutes of histamine administration, was reduced significantly in diabetic groups...

Comparative histological study of atherosclerotic lesions and microvascular changes in amputated lower limbs of diabetic and non-diabetic patients / Estudo histológico comparativo das lesões ateroscleróticas e alterações microvasculares em membros inferiores amputados de pacientes diabéticos e não-diabéticos

OBJETIVE: To perform a comparative analysis of atherosclerotic lesions and capillaries changes in diabetic and nondiabetic patients. METHODS: Leg arteries and skin of 57 amputated lower limbs of diabetic (47.3 percent) and nondiabetic patients were histologically examined. The percentage of arterial stenosis of infrapopliteal arteries and the histological classification of atherosclerotic lesions were determined. Capillary thickening was classified into four categories. RESULTS: Diabetic group showed more than 75 percent stenosis in 57 percent (vs. 56 percent in nondiabetic) of the anterior tibial; 78 percent (vs. 68 percent) of the posterior tibial; 58 percent (vs. 50 percent) of the peroneal leg arteries. Diabetic and nondiabetic patients have predominance of type VI atherosclerotic lesions. The comparison of both groups showed no significant differences in atherosclerotic lesions. Diabetic patients had significantly more PAS positive capillary thickening (63 percent vs. 23 percent). CONCLUSIONS: There were no differences in histological characteristics of atherosclerosis between the two groups. Capillary thickening has been more observed in diabetics.

OBJETIVO: Comparar as lesões ateroscleróticas das extremidades de diabéticos e não-diabéticos, estudando a ocorrência de espessamento capilar. MÉTODOS: Examinou-se segmentos arteriais e da derme de 57 membros inferiores amputados de diabéticos (47,3 por cento) e não-diabéticos. Analisou-se a porcentagem de estenose das artérias infra-poplíteas e a classificação histológica da placa. A presença de espessamento capilar foi classificada em quatro categorias. RESULTADOS: Entre os diabéticos 57 por cento (versus 56 por cento dos não-diabéticos) apresentavam estenose maior que 75 por cento da artéria tibial anterior; 78 por cento (versus 68 por cento) da tibial posterior; 58 por cento (versus 50 por cento) da fibular. Houve predominância em ambos de lesões ateroscleróticas do tipo VI. Comparando os grupos, não houve diferença significante na porcentagem de obstrução arterial ou na classificação da placa aterosclerótica. Os diabéticos apresentaram significativamente mais espessamento capilar (63 por cento versus 23 por cento). CONCLUSÕES: Não houve diferença nas características das lesões ateroscleróticas em diabéticos e não-diabéticos. O espessamento capilar foi mais prevalente entre os diabéticos.

Retinal vascular signs in diabetes and hypertension - review

The retinal vasculature is a unique site where the microcirculation can be noninvasively imaged in vivo. This presents an opportunity to study otherwise inaccessible structural features of the microcirculation. Recently, a number of population-based studies have developed quantitative methods of measuring these retinal signs, and investigated how these signs relate to metabolic disorders such as diabetes, hypertension, obesity, and metabolic syndrome. These studies have reported fairly consistent associations of retinopathy lesions, arteriolar narrowing and venular dilation with these metabolic disorders, suggesting a microvascular component in either the pathogenesis or manifestation of these disorders. Further, several of these signs have been associated with future risk of cardiovascular outcomes, such as coronary heart disease and stroke, independently of traditional risk factors. This review will examine in detail the evidence linking retinal vascular signs with metabolic disorders and discuss their implications for research and clinical practice.

A vasculatura retiniana apresenta uma oportunidade única de observação não-invasiva da microcirculação e de suas estruturas in vivo. Recentemente, uma série de estudos populacionais desenvolveu métodos quantitativos de observação destes sinais retinianos e suas relações com distúrbios metabólicos, tais como diabetes, obesidade, hipertensão arterial e síndrome metabólica. Esses estudos demonstraram associações das lesões retinianas, entre elas estreitamento arteriolar e dilatação venular, com essas alterações metabólicas, sugerindo um componente microvascular na patogênese ou na manifestação destes distúrbios. Ainda, vários destes sinais foram associados com risco de doença cardiovascular, tais como doença arterial coronariana e acidente vascular cerebral independente dos fatores de risco clássicos. Esta revisão discute em detalhes as evidências entre os sinais retinianos e os distúrbios metabólicos e suas possíveis implicações na pesquisa e na prática clínica.

Glomerulonefritis rápidamente progresiva y perforación intestinal por poliangeítis microscópica / Rapidly progressive glomerulonephritis and intestinal perforation for microscopic polyangiitis

La Poliangeítis Microscópica (PAM) consiste en una vasculitis necrotizante que afecta a vasos muy pequeños, principalmente arteriolas de pequeño calibre, capilares y vénulas, fundamentalmente capilares glomerulares y en ocasiones, capilares pulmonares. El tracto gastrointestinal (TGI) también puede estar comprometido en la PAM con tasas reportadas de 30porcentaje-56porcentaje. Clínicamente, el espectro de síntomas gastrointestinales es amplio, variando desde dolor abdominal leve y transitorio hasta complicaciones que amenazan la vida y requieren cirugía de urgencia, por ejemplo, peritonitis, infarto intestinal, o hemorragia. Sin embargo, el sangrado intestinal masivo es una manifestación poco frecuente en la historia natural de la PAM. En verdad, al menos para PAM, el compromiso gastrointestinal severo ha sido identificado como un factor independiente asociado con pobre pronóstico. Informamos el caso de una mujer de 22 años que desarrolló glomerulonefritis rápidamente progresiva (GNRP) y perforación intestinal por PAM...

Tortuosy of terminal arterioles in the basal gangli is increased in status lacunaris

El objetivo de este estudio fue evaluar la participación de las arteriolas pequeñas (diámetro entre las 26 y 90 µm) y terminales (diámetro entre las 10 y 25 µm) en el status lacunaris de los ganglios de la base; así también clasificar los perfiles de presentación de los vasos tortuosos por su morfología. El procedimiento de estudio consistió en secciones de parafina, 40 µm de grueso de los ganglios de la base de pacientes autopsiados con edad mayor de 45 años, coloreados por la técnica de PAS. Un microscopio tridimensional, R400 (edge) se utilizó para evaluar las estructuras de los vasos sanguíneos. Seis patrones de perfiles tortuosos fueron identificados: simple acodadura, asa, nudo, ovillo, resorte y ondulante, así como también sus combinaciones. Las arteriolas tortuosas en los ganglios de la base estuvieron presentes en aquellos casos tanto del grupo control como del grupo status lacunaris. Sin embargo, el análisis estadístico con la prueba de la t de Student reveló un incremento significante en el número de microcampos conteniendo arteriolas terminales tortuosas en el grupo con status lacunaris (promedio de 7,50 ± 4,62) versus el grupo control (promedio de 2,92 ± 1,38) (p= 0,001). El riesgo para status lacunaris fue asociado con el incremento en la frecuencia de las arteriolas terminales (Odd ratio=1,94; 95 por ciento-Intervalo de confianza= 1,17-3,22) (p= 0,008) pero no con pequeñas arteriolas (Odd ratio= 1,64; 95 por ciento)-Intervalo de confianza= 0,62-4,38) (p= 0,39). Nuestros resultados sugieren que un incremento en el número de arteriolas tortuosas terminales está asociado con el status lacunaris. Seis patrones característicos de los perfiles tortuosos así como su combinación fueron también identificados

Estudo histomorfométrico da fibrose periarteriolar miocárdica em alcoolistas crônicos / A morphometric study of periarteriolar myocardial fibrosis in chronic alcoholics

O uso crônico abusivo do álcool causa uma ampla variedade de alterações sistêmicas, entre elas cardiopatia. A doença alcoólica cardíaca (DAC) apresenta-se com um quadro clínico bastante similar ao da miocardiopatia dilatada, mas admite-se que as manifestações clínicas e as lesões histológicas são mais discretas e, aparentemente, possuem certo potencial de regressão. Fibrose com distribuição e intensidade variáveis temsido uma alteração frequentemente observada. Neste trabalho foi realizado um estudo histoformométrico da fibrose periarteiolar miocárdica em dezenove indivíduos alcoolistas autopsiados na cidade do Recife. O grupo controle de doze indivíduos sem história de alcoolismo. Preparações histológicas com 4im de espessura obtidas da parede livre do ventrículo esquerdo foram coradas pelo tricrômico de Masson e examinadas com o Sistema Interativo de Análise de Imagens MOP VIDEOPLAN (Kontron Eletronic Group, Munique). A área (ìm²) periarteriolar ocupada por colágeno foi significativamente maior no grupo alcoolista do que nos controles (4.67,2 ñ 2.753,2 vs 2.300,8 ñ 1.265,4; P<0,05). Os resultados indicam que, de fato, ocorre alterações fibróticas em torno de arteróolas na DAC. As modificações do arcabouço colágeno cardíaco têm repercussões funcionais relevantes e podem resultar dos efeitos tóxicos diretos do álcool e de seus subprodutos sobre as miocélulas, ou de lesões na microcirculação miocárdica

Estudo Morfométrico da rede arteriolar miocárdica em indivíduos alcoolistas crônicos / Morphometric study of myocardic arteriolar net in chronic alcaholic patients

A patogênese da doença alcoolica cardíaca não é completamente conhecida. Segundo uma das hipóteses, as lesões miocárdicas resultariam de alterações na parede dos vasos. Para avaliar possíveis alterações vaculares parietais, foi realizado estudo morfométrico de arteíolas miocárdica em doze alcoolistas crônicos (nove homens e três mulheres, com idade variando de 24 a 45 anos) e em oito controles (três homens e cinco mulheres, com idade variando entre 20 e 39 anos). Cortes histólogicos de seções transversais, longitudinais e oblíquas da parede livre do ventrículo esuerdo foram analisados em sistema semi-automático de análise de imagem. Não se obseervaram diferenças estatisticamente significativas na espessura da parede articular entre os dois grupos. É possível, portanto, que alteraçõess vasculares, pelo nenos no que se refere a rede arteriolar miocárdica, não contribuam significativamente para a doença alcoólica cardíaca