RESUMEN
BACKGROUND: A predictor of neonatal mortality in infants with congenital diaphragmatic hernia (CDH) is disrupted pulmonary vascular development, clinically expressed as pulmonary hypertension. OBJECTIVE: To determine if prenatal corticosteroids and phosphodiesterase-5 (PDE-5) inhibitors have a beneficial effect on pulmonary vascular development in CDH lungs. METHODS: We induced CDH in fetal rats by giving nitrofen. We then exposed them to dexamethasone or to sildenafil. We separated them into three groups: (1) DEX, 4 pregnant rats received dexamethasone at days E16, E18 and E20; (2) SILD, 4 pregnant rats received sildenafil and L-arginine between E14 and E22, and (3) placebo. We then analyzed the lung of each fetus with CDH at E22. We examined the number of arterioles and arteries, and their percent of medial wall thickness (%MWT). RESULTS: We obtained 30 CDH-positive fetuses. We analyzed 3,560 arterioles and 211 arteries. SILD showed a significant increase in the number of arterioles, but no significant increase in the number of arteries. No change was noted in the arteriolar %MWT. In contrast, DEX showed significant decreases in the number of arterioles and arteries and a significant increase in %MWT. CONCLUSIONS: PDE-5 inhibitors may improve pulmonary arteriolar development in fetuses with CDH. In contrast, prenatal corticosteroids could have deleterious effects on arteriolar and arterial development in CDH lungs.
Asunto(s)
Dexametasona/farmacología , Glucocorticoides/farmacología , Hernias Diafragmáticas Congénitas/tratamiento farmacológico , Hipertensión Pulmonar/prevención & control , Inhibidores de Fosfodiesterasa 5/farmacología , Piperazinas/farmacología , Sulfonamidas/farmacología , Actinas/metabolismo , Animales , Animales Recién Nacidos , Femenino , Hernias Diafragmáticas Congénitas/complicaciones , Hernias Diafragmáticas Congénitas/fisiopatología , Hipertensión Pulmonar/etiología , Inmunohistoquímica , Neovascularización Fisiológica/efectos de los fármacos , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Embarazo , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Arteria Pulmonar/ultraestructura , Purinas/farmacología , Ratas , Ratas Sprague-Dawley , Citrato de Sildenafil , Túnica Íntima/efectos de los fármacos , Túnica Íntima/metabolismo , Túnica Íntima/patología , Túnica Íntima/ultraestructuraRESUMEN
BACKGROUND: Vitamin A deficiency induces activation of NF-kB and impairs activities of antioxidant enzymes in aorta. AIM OF THE STUDY: We study the effect of vitamin A deficiency on the aorta histoarchitecture and the possibly contribution of its prooxidant and inflammatory effects to artery alterations. METHODS: Twenty-one-day-old Wistar male rats were fed during 3 months with vitamin A-deficient diet (-A, n = 8) or the same diet containing 8 mg of retinol palmitate/kg of diet (+A, control, n = 8). In aortas, thiobarbituric reactive substances and reduced glutathione levels were measured by spectrophotometry. Expressions of TNF-alpha, NOX-2, VCAM-1, and TGF-beta1 were assessed by RT-PCR and Western Blot. The morphology of aorta was examined by light and transmission electron microscopy. RESULTS: In -A rats, high levels of TBARS in serum and aorta and low levels of GSH in aorta were found. An increased expression of TNF-alpha, NOX-2, VCAM-1, and TGF-beta1 in aorta from -A rats was observed. Examination of the intimal layer by light microscopy indicated the presence of an irregular surface in -A aortas. TEM studies showed large vacuoles and multivesicular bodies along the endothelium and also multivesicular bodies in the subendothelial space of aortas from -A rats. Furthermore, the histological appearance of internal elastic lamina was different from control. Small vesicles in the medial layer were observed in aortas from vitamin A-deficient rats. CONCLUSIONS: Vitamin A deficiency produces histoarchitectural alterations in aorta, which can be associated, at least in part, to the oxidative stress and inflammation induced by vitamin A deficiency.
Asunto(s)
Aorta/inmunología , Aorta/ultraestructura , Estrés Oxidativo , Vasculitis/etiología , Deficiencia de Vitamina A/patología , Deficiencia de Vitamina A/fisiopatología , Animales , Aorta/metabolismo , Citocinas/genética , Citocinas/metabolismo , Regulación de la Expresión Génica , Glutatión/metabolismo , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Cuerpos Multivesiculares/ultraestructura , NADPH Oxidasa 2 , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Oxidación-Reducción , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Ratas Wistar , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Túnica Íntima/ultraestructura , Vacuolas/ultraestructura , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismo , Deficiencia de Vitamina A/inmunología , Deficiencia de Vitamina A/metabolismoAsunto(s)
Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/prevención & control , Medicina Preventiva , Dislipidemias/diagnóstico , Enfermedades Renales , Factores de Riesgo , Túnica Íntima/ultraestructuraRESUMEN
This study aimed to evaluate the effect of rosuvastatin upon structural and ultrastructural aortic remodeling in a rat model of hypertension induced by NO synthase blockade. Wistar rats were divided into 4 groups: Control group (C); control treated with rosuvastatin 20mg/kg/day (CR); L-NAME group 40 mg/kg/day (LN) and L-NAME treated with rosuvastatin (LNR) (same doses). Body mass and blood pressure were measured weekly; the experiment lasted 5 weeks. L-NAME administration augmented blood pressure (BP) in the LN group in comparison to the C group (123.3 vs. 180.5 mm Hg at week 5). In LNR rats, rosuvastatin slightly attenuated BP rise, but it had no effect on the BP of CR group. Intima and media thickening of the thoracic aorta were observed in the LN group, and increased elastic fiber content as well. Rosuvastatin prevented all these alterations as seen in the LNR group. Ultrastructural changes due to L-NAME intake (intracellular vesicles and altered membrane morphology in endothelial cells, extracellular matrix deposition, and cytoplasmatic projections from smooth muscle cells toward the internal elastic lamina) were also prevented by rosuvastatin. All in all, rosuvastatin administration is capable of attenuating ultrastructural aortic wall remodeling in NO-deficient rats despite small changes in blood pressure.
Asunto(s)
Aorta Torácica/efectos de los fármacos , Fluorobencenos/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Hipertensión/patología , Óxido Nítrico/deficiencia , Pirimidinas/farmacología , Sulfonamidas/farmacología , Animales , Aorta Torácica/metabolismo , Aorta Torácica/ultraestructura , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Células Endoteliales/ultraestructura , Fluorobencenos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Inmunohistoquímica , Lípidos/sangre , Microscopía Electrónica de Transmisión , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa de Tipo III/antagonistas & inhibidores , Pirimidinas/uso terapéutico , Ratas , Ratas Wistar , Rosuvastatina Cálcica , Sulfonamidas/uso terapéutico , Túnica Íntima/efectos de los fármacos , Túnica Íntima/metabolismo , Túnica Íntima/ultraestructuraRESUMEN
La disfunción endotelial (DE) se presenta en pacientes con hipercolesterolemia, hipertensión arterial, obesidad y diabetes mellitus. Evidencias sugieren un papel de los glicosaminoglicanos en la DE. Evaluamos el efecto del sulodexide (SLD), un glicosaminoglicano utilizado en el tratamiento de la albuminuria y la enfermedad isquémica en pacientes diabéticos, sobre la relajación arterial y los cambios morfológicos en un modelo experimental de diabetes tipo 1. La diabetes se indujo a ratas Sprague Dawley administrando estreptozotocina (STZ), 60 mg/kg, i.v. Los animales fueron distribuidos en los siguientes grupos: I= control, II= diabéticas, III: control + sulodexide, IV= diabéticas + sulodexide (15 mg/kg/día s.c). A los 3 meses fueron sacrificados, las aortas extraídas para evaluar la relajación vascular inducida por acetilcolina (Ach) y nitroprusiato de sodio en anillos precontraídos con fenilefrina. Fueron evaluadas histológicamente mediante microscopía de luz y coloraciones diversas. El SLD in vitro no modificó la tensión basal de los anillos arteriales en reposo o precontraídos con fenilefrina. La diabetes disminuyó la capacidad de relajación arterial en respuesta a la Ach en un 28,8-35,1% vs control, efecto que fue prevenido por SLD. No se observó diferencia significativa en la relajación inducida por nitroprusiato sódico entre los grupos. El estudio histológico en los animales diabéticos mostró alteraciones estructurales, particularmente en la íntima y la adventicia, cambios que fueron prevenidos por el tratamiento con SLD. Nuestros resultados apoyan la potencial utilidad terapéutica del SLD en el tratamiento de la disfunción endotelial.
Endothelial dysfunction (ED) is observed in patients with hypercholesterolemia, arterial hypertension, obesity and diabetes mellitus. Recent evidences suggest the involvement of glycosaminoglycans(GSG) in ED. We evaluated the effect of sulodexide (SLD), a natural GSG used in albuminuria and ischemic diabetes treatment, on arterial relaxation and vascular morphological changes in a diabetic type I model. Diabetes was induced, in Sprague-Dawley rats by streptozotocine (STZ) administration, 60 mg, iv. Rats were divided into four groups; I: control, II: diabetics, III: control + SLD, IV: diabetics treated with SLD (15 mg/day). After three months, phenylephrine precontracted aortic rings were used to evaluate acetylcholine (ACh) and sodium nitroprusside (NPS) relaxation capacities. Light microscopy of aorta was done with several staining procedures. In vitro, SLD did not change smooth muscle tone in resting or phenylephrine precontracted aortic rings. In diabetic rats, ACh relaxation was 28.8-35.1% lower than in control rats. Diabetic rats treated with SLD showed aortic ACh relaxation similar to control rats. No significative statistical difference was found in endothelium-independent NPS relaxation, between the different groups. Light microscopy histological studies revealed important morphological alterations, particularly in intima and adventitia layers of aortic artery; those changes were dramatically reversed in SLD treated rats. Our experiments support the conclusion that SLD is a potential drug for improving endothelial dysfunction in diabetes.
Asunto(s)
Animales , Masculino , Ratas , Aorta/efectos de los fármacos , Enfermedades de la Aorta/prevención & control , Diabetes Mellitus Experimental/tratamiento farmacológico , Angiopatías Diabéticas/prevención & control , Endotelio Vascular/efectos de los fármacos , Glicosaminoglicanos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Vasodilatación/efectos de los fármacos , Acetilcolina/farmacología , Aorta/patología , Aorta/fisiopatología , Enfermedades de la Aorta/etiología , Enfermedades de la Aorta/patología , Enfermedades de la Aorta/fisiopatología , Evaluación Preclínica de Medicamentos , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/fisiopatología , Angiopatías Diabéticas/etiología , Angiopatías Diabéticas/patología , Angiopatías Diabéticas/fisiopatología , Endotelio Vascular/ultraestructura , Glicosaminoglicanos/metabolismo , Glicosaminoglicanos/farmacología , Hipoglucemiantes/farmacología , Nitroprusiato/farmacología , Ratas Sprague-Dawley , Túnica Íntima/efectos de los fármacos , Túnica Íntima/ultraestructuraRESUMEN
The Kronos Early Estrogen Prevention Study (KEEPS) is a randomized clinical and controlled study, with the objective of clarifying the controversy that arisen previous studies about the risk-benefit factor with use of estrogens in postmenopausal women. Healthy women aged 42-58 years who are within 36 months of their last menstrual period have been recruited to receive either oral estrogens or patches of estradiol; in addition both groups are given oral micronized progesterone for 11 days of each month. Outcomes will be carotid intimae medial thickness and the accrual of coronary calcium; collaterally subrogate outcomes will be lipoproteins concentrations, coagulation markers, bone densitometry, mammography, skin characteristics and cognitive evaluation. The hypothesis consists in the presence of a window of therapeutic opportunity for the use of estrogens in low dose in healthy women with recent menopause.
Asunto(s)
Estradiol/uso terapéutico , Terapia de Reemplazo de Estrógeno , Menopausia , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Administración Cutánea , Administración Oral , Anciano , Densidad Ósea , Calcinosis/diagnóstico por imagen , Arterias Carótidas/ultraestructura , Cognición , Angiografía Coronaria , Estradiol/administración & dosificación , Estradiol/efectos adversos , Terapia de Reemplazo de Estrógeno/efectos adversos , Terapia de Reemplazo de Estrógeno/métodos , Femenino , Humanos , Lipoproteínas/sangre , Mamografía , Persona de Mediana Edad , Progesterona/administración & dosificación , Progesterona/efectos adversos , Medición de Riesgo , Tomografía Computarizada Espiral , Túnica Íntima/ultraestructuraAsunto(s)
Humanos , Arterias Carótidas/ultraestructura , Arterias Carótidas , Enfermedades de las Arterias Carótidas/diagnóstico , Enfermedades de las Arterias Carótidas/prevención & control , Aterosclerosis/diagnóstico , Aterosclerosis , Índice Tobillo Braquial , Factores de Riesgo , Túnica Íntima/ultraestructura , Ultrasonografía Doppler de Pulso , Enfermedades Vasculares Periféricas/diagnóstico , Enfermedades Vasculares Periféricas/prevención & control , Aorta/fisiología , Presión SanguíneaRESUMEN
Los sistemas de prevención cardiovascular basados en la determinación de factores de riesgo presentan limitaciones para cuantificar el riesgo de un sujeto. Los factores de riesgo son predictores de aterosclerosis en la población, pero fallan en identificar qué sujetos desarrollarán la enfermedad y/o tendrán eventos cardiovasculares; los que frecuentemente se presentan en sujetos de riesgo bajo o intermedio. En este contexto, guías/consensos sugieren realizar estudios no invasivos en sujetos asintomáticos para estratificar el riesgo individual, detectar y tratar la aterosclerosis en etapa subclínica. Para ello se han propuesto diferentes abordajes que permiten caracterizar la estructura y/o función arterial por métodos no invasivos, brindando información complementaria, que adiciona a la obtenida con la determinación de los factores de riesgo. En Uruguay, recientemente se creó un centro universitario interdisciplinario (CUiiDARTE, Centro Universitario de Investigación, Innovación y Diagnóstico Arterial), que tiene entre sus objetivos implementar técnicas no invasivas para la evaluación integral de la estructura y función arterial, posibilitando dar respuesta a la necesidad de estratificación individualizada del riesgo cardiovascular y detección de aterosclerosis subclínica. En este trabajo se presenta el abordaje de evaluación vascular empleado en CUiiDARTE y basados en nuestra experiencia, se discuten aspectos teóricos y prácticos de los test no invasivos utilizados y parámetros estudiados.
Traditional risk factors-guided cardiovascular prevention/treatment has clear limitations in individual subjects management. Often, individuals with similar risk factor profiles have differences in the atherosclerosis development and are at different cardiovascular risk. Therefore, while risk factors are good predictors of atherosclerosis in a population, they cannot identify who will develop the disease and/or will have a cardiovascular event. In this context, there have been published guidelines calling for non-invasive atherosclerosis screening and risk stratification in asymptomatic subjects. Several approaches have been proposed for the vascular evaluation, and although the screening tests used vary among laboratories, in general terms their are underused. In Uruguay, it was recently created an interdisciplinary university center (CUiiDARTE, Centro Universitario de Investigación, Innovación y Diagnóstico Arterial), which has as a main aim the implementation of non-invasive techniques to evaluate the arterial structural and functional properties, that could allow stratifying the individual cardiovascular risk and identifying sub-clinical atherosclerosis. In this work we present the integral vascular approach used in CUiiDARTE and based in our experience we discuss, theoretical and practical issues related with the tests performed and parameters calculated.
Asunto(s)
Humanos , Arterias Carótidas/ultraestructura , Arterias Carótidas , Aterosclerosis/diagnóstico , Aterosclerosis , Enfermedades de las Arterias Carótidas/diagnóstico , Enfermedades de las Arterias Carótidas/prevención & control , Índice Tobillo Braquial , Aorta/fisiología , Enfermedades Vasculares Periféricas/diagnóstico , Enfermedades Vasculares Periféricas/prevención & control , Factores de Riesgo , Presión Sanguínea , Túnica Íntima/ultraestructura , Ultrasonografía Doppler de PulsoRESUMEN
Endothelial dysfunction (ED) is observed in patients with hypercholesterolemia, arterial hypertension, obesity and diabetes mellitus. Recent evidences suggest the involvement of glycosaminoglycans (GSG) in ED. We evaluated the effect of sulodexide (SLD), a natural GSG used in albuminuria and ischemic diabetes treatment, on arterial relaxation and vascular morphological changes in a diabetic type I model. Diabetes was induced, in Sprague-Dawley rats by streptozotocine (STZ) administration, 60 mg, i.v. Rats were divided into four groups; I: control, II: diabetics, III: control + SLD, IV: diabetics treated with SLD (15 mg/day). After three months, phenylephrine precontracted aortic rings were used to evaluate acetylcholine (ACh) and sodium nitroprusside (NPS) relaxation capacities. Light microscopy of aorta was done with several staining procedures. In vitro, SLD did not change smooth muscle tone in resting or phenylephrine precontracted aortic rings. In diabetic rats, ACh relaxation was 28.8-35.1% lower than in control rats. Diabetic rats treated with SLD showed aortic ACh relaxation similar to control rats. No significative statistical difference was found in endothelium-independent NPS relaxation, between the different groups. Light microscopy histological studies revealed important morphological alterations, particularly in intima and adventitia layers of aortic artery; those changes were dramatically reversed in SLD treated rats. Our experiments support the conclusion that SLD is a potential drug for improving endothelial dysfunction in diabetes.
Asunto(s)
Aorta/efectos de los fármacos , Enfermedades de la Aorta/prevención & control , Diabetes Mellitus Experimental/tratamiento farmacológico , Angiopatías Diabéticas/prevención & control , Endotelio Vascular/efectos de los fármacos , Glicosaminoglicanos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Vasodilatación/efectos de los fármacos , Acetilcolina/farmacología , Animales , Aorta/patología , Aorta/fisiopatología , Enfermedades de la Aorta/etiología , Enfermedades de la Aorta/patología , Enfermedades de la Aorta/fisiopatología , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/fisiopatología , Angiopatías Diabéticas/etiología , Angiopatías Diabéticas/patología , Angiopatías Diabéticas/fisiopatología , Evaluación Preclínica de Medicamentos , Endotelio Vascular/ultraestructura , Glicosaminoglicanos/metabolismo , Glicosaminoglicanos/farmacología , Hipoglucemiantes/farmacología , Masculino , Nitroprusiato/farmacología , Ratas , Ratas Sprague-Dawley , Túnica Íntima/efectos de los fármacos , Túnica Íntima/ultraestructuraRESUMEN
Structural vascular changes in two-kidney, one-clip (2K-1C) hypertension may result from increased matrix metalloproteinase (MMP)-2 activity. MMP-2 activation is regulated by other MMPs, including transmembrane-MMPs, and by tissue inhibitors of MMPs (TIMPs). We have investigated the localization of MMP-2, -9, -14, and TIMPs 1-4 in hypertensive aortas and measured their levels by zymography/Western blotting and immunohistochemistry. Gelatinolytic activity was assayed in tissues by in situ zymography. Sham-operated and 2K-1C hypertensive rats were treated with doxycycline (or vehicle) for 8 weeks, and the systolic blood pressure was monitored weekly. Doxycycline attenuated 2K-1C hypertension (165 + or - 11.7 mmHg versus 213 + or - 7.9 mm Hg in hypertensive controls, P<0.01), and completely prevented increase in the thicknesses of the media and the intima in 2K-1C animals (P<0.01). Increased amounts of MMP-2, -9, and -14 were found in hypertensive aortas, as well as enhanced gelatinolytic activity. A gradient in the localization of MMP-2, -9, and -14 was found, with increased amounts detected in the intima, at sites with higher gelatinolytic activity. Doxycycline attenuated hypertension induced increases in all the 3 investigated MMPs in both the media and the intima (all P<0.05), but it did not change the amounts of TIMPs 1-4 (P>0.05). Therefore, an imbalance between increased amounts of MMPs at the tissue level without a corresponding increase in the quantities of TIMPs, particularly in the intima and inner media layers, appears to account for the increased proteolytic activity found in 2K-1C hypertension-induced maladaptive vascular remodeling.
Asunto(s)
Matriz Extracelular/metabolismo , Hipertensión/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Animales , Aorta/metabolismo , Aorta/patología , Presión Sanguínea/fisiología , Western Blotting , Doxiciclina/farmacología , Inhibidores Enzimáticos/farmacología , Hipertensión/embriología , Hipertensión/patología , Inmunohistoquímica , Masculino , Tamaño de los Órganos/fisiología , Ratas , Ratas Wistar , Túnica Íntima/metabolismo , Túnica Íntima/ultraestructuraRESUMEN
OBJECTIVE: To observe the effects of consuming repeatedly heated soy oil on the aortic tissues of estrogen-deficient rats. METHODS: Thirty female Sprague Dawley rats (200-250 g) were divided equally into five groups. One group served as the normal control (NC) group. The four treated groups were ovariectomized and were fed as follows: 2% cholesterol diet (OVXC); 2% cholesterol diet + fresh soy oil (FSO); 2% cholesterol diet + once-heated soy oil (1HSO); and 2% cholesterol diet + five-times-heated soy oil (5HSO). After four months, the rats were sacrificed, and the aortic tissues were obtained for histological studies. RESULTS: After four months of feeding, the NC, FSO and 1HSO groups had a lower body weight gain compared to the OVXC and 5HSO groups. The tunica intima/media ratio in the 5HSO group was significantly thicker (p < 0.05) compared to the NC, OVXC and FSO groups. Electron microscopy showed that endothelial cells were normally shaped in the FSO and NC groups but irregular in the 1HSO and 5HSO groups. A greater number of collagen fibers and vacuoles were observed in the 5HSO group compared to the other treatment groups. CONCLUSIONS: Fresh soy oil offered protection in the estrogen-deficient state, as these rats had similar features to those of the NC group. The damage to the tunica intima and the increase in the ratio of tunica intima/media thickness showed the deleterious effect of consuming repeatedly heated soy oil in castrated female rats.
Asunto(s)
Aorta Torácica/efectos de los fármacos , Aterosclerosis/prevención & control , Estrógenos/deficiencia , Aceite de Soja/farmacología , Animales , Aorta Torácica/ultraestructura , Aterosclerosis/patología , Grasas Insaturadas en la Dieta/farmacología , Modelos Animales de Enfermedad , Femenino , Calor , Ovariectomía , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Túnica Íntima/ultraestructuraRESUMEN
OBJECTIVE: To observe the effects of consuming repeatedly heated soy oil on the aortic tissues of estrogen-deficient rats. METHODS: Thirty female Sprague Dawley rats (200- 250 g) were divided equally into five groups. One group served as the normal control (NC) group. The four treated groups were ovariectomized and were fed as follows: 2 percent cholesterol diet (OVXC); 2 percent cholesterol diet + fresh soy oil (FSO); 2 percent cholesterol diet + once-heated soy oil (1HSO); and 2 percent cholesterol diet + five-times-heated soy oil (5HSO). After four months, the rats were sacrificed, and the aortic tissues were obtained for histological studies. RESULTS: After four months of feeding, the NC, FSO and 1HSO groups had a lower body weight gain compared to the OVXC and 5HSO groups. The tunica intima/media ratio in the 5HSO group was significantly thicker (p < 0.05) compared to the NC, OVXC and FSO groups. Electron microscopy showed that endothelial cells were normally shaped in the FSO and NC groups but irregular in the 1HSO and 5HSO groups. A greater number of collagen fibers and vacuoles were observed in the 5HSO group compared to the other treatment groups. CONCLUSIONS: Fresh soy oil offered protection in the estrogen-deficient state, as these rats had similar features to those of the NC group. The damage to the tunica intima and the increase in the ratio of tunica intima/media thickness showed the deleterious effect of consuming repeatedly heated soy oil in castrated female rats.
Asunto(s)
Animales , Femenino , Ratas , Aorta Torácica/efectos de los fármacos , Aterosclerosis/prevención & control , Estrógenos/deficiencia , Aceite de Soja/farmacología , Aorta Torácica/ultraestructura , Aterosclerosis/patología , Modelos Animales de Enfermedad , Grasas Insaturadas en la Dieta/farmacología , Calor , Ovariectomía , Distribución Aleatoria , Ratas Sprague-Dawley , Túnica Íntima/ultraestructuraRESUMEN
BACKGROUND AND AIM: The measurement of carotid intima-media thickness (cIMT) has been used as a marker of arterial wall disease. Manual measurements have been performed in most epidemiological studies, but, due to the introduction of new technologies, automated software has been increasingly used. This study aimed to compare manual versus automated cIMT measurements in common carotid (CC), bifurcation (BIF), and internal carotid (IC). METHODS: Automated and manual cIMT measurements were performed online in 43 middle-aged females. Carotid segment measurements were compared by Bland-Altman plot and the variation and repeatability coefficients between observers were also determined for comparison. RESULTS: The average timespan for manual measurements (57.30 s) were significantly higher than for automated measurements (2.52 s). There were no systematic errors between methods in any carotid segments. The variation coefficient was 5.54% to 6.34% for CC and BIF, 9.76% for IC, and absolute differences were 85% below 0.1 mm and 70% below 0.05 mm. Interobserver agreement showed no systematic error. The variation and the repeatability coefficients were better for the automated than manual measures. CONCLUSION: Although both methods are reliable for cIMT measurements, the automated technique allows faster evaluation with lesser variability for all carotid segments currently used in atherosclerosis research.
Asunto(s)
Arteria Carótida Común/diagnóstico por imagen , Arteria Carótida Interna/diagnóstico por imagen , Túnica Íntima/ultraestructura , Túnica Media/diagnóstico por imagen , Adulto , Automatización de Laboratorios , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Persona de Mediana Edad , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , UltrasonografíaRESUMEN
PURPOSE: This study sought to evaluate the efficiency of glycol methacrylate-embedding medium to detect morphological alterations of human saphenous vein submitted to brief and crescent pressurizations. METHODS: Saphenous veins of 20 CABG patients were randomly distributed into four experimental groups (control, 100, 200 and 300 mmHg pressures during 15 seconds). To quantify the percentage of endothelium spread over vein surface a microscope magnification of 100x was used for measurements. Morphometric analysis was performed using videomicroscopy with the Leica Qwin software in conjunction with a Leica microscope, videocamera, and an on-line computer. RESULTS: A slight tendency of quantitative increase was observed in all parameters including percentage of endothelium spread over vein surface and thickness of saphenous vein walls (intima and media layers). CONCLUSIONS: The glycol methacrylate-embedding allowed sections with adequate resolution of structural details and revealed to be an extremely useful method to study pressurized human saphenous veins.
Asunto(s)
Metacrilatos , Adhesión en Plástico/métodos , Presión , Vena Safena/anatomía & histología , Túnica Íntima/ultraestructura , Humanos , Microscopía por Video/métodos , Vena Safena/ultraestructuraRESUMEN
PURPOSE: This study sought to evaluate the efficiency of glycol methacrylate-embedding medium to detect morphological alterations of human saphenous vein submitted to brief and crescent pressurizations. METHODS: Saphenous veins of 20 CABG patients were randomly distributed into four experimental groups (control, 100, 200 and 300 mmHg pressures during 15 seconds). To quantify the percentage of endothelium spread over vein surface a microscope magnification of 100x was used for measurements. Morphometric analysis was performed using videomicroscopy with the Leica Qwin software in conjunction with a Leica microscope, videocamera, and an on-line computer. RESULTS: A slight tendency of quantitative increase was observed in all parameters including percentage of endothelium spread over vein surface and thickness of saphenous vein walls (intima and media layers). CONCLUSIONS: The glycol methacrylate-embedding allowed sections with adequate resolution of structural details and revealed to be an extremely useful method to study pressurized human saphenous veins.
OBJETIVO: Avaliar a inclusão em glicol metacrilato para estudar alterações morfológicas de veias safenas humanas submetidas a pressurizações breves e crescentes. MÉTODOS: Veias safena de 20 pacientes submetidos a cirurgia de revascularização do miocárdio foram distribuídas ao acaso em quatro grupos experimentais (controle, pressões de 100, 200 e 300 mmHg durante 15 segundos). Para quantificar a percentagem da superfície venosa recoberta por endotélio utilizou-se o aumento de 100x. A análise morfométrica foi realizada utilizando-se videomicroscopia com auxílio do software Leica Qwin em conjunto com um microscópio Leica e videocâmera, acoplados a um computador. RESULTADOS: Observou-se uma leve tendência de aumento quantitativo de todos os parâmetros avaliados, incluindo a percentagem de superfície recoberta por endotélio e a espessura das paredes das veias safenas. CONCLUSÕES: A inclusão em glicol metracrilato permitiu secções com adequada resolução dos detalhes estruturais, revelando-se um método extremamente útil para o estudo de veias safenas humanas pressurizadas.
Asunto(s)
Humanos , Metacrilatos , Presión , Adhesión en Plástico/métodos , Vena Safena/anatomía & histología , Túnica Íntima/ultraestructura , Microscopía por Video/métodos , Vena Safena/ultraestructuraRESUMEN
PURPOSE: This study sought to evaluate the efficiency of glycol methacrylate-embedding medium to detect morphological alterations of human saphenous vein submitted to brief and crescent pressurizations. METHODS: Saphenous veins of 20 CABG patients were randomly distributed into four experimental groups (control, 100, 200 and 300 mmHg pressures during 15 seconds). To quantify the percentage of endothelium spread over vein surface a microscope magnification of 100x was used for measurements. Morphometric analysis was performed using videomicroscopy with the Leica Qwin software in conjunction with a Leica microscope, videocamera, and an on-line computer. RESULTS: A slight tendency of quantitative increase was observed in all parameters including percentage of endothelium spread over vein surface and thickness of saphenous vein walls (intima and media layers). CONCLUSIONS: The glycol methacrylate-embedding allowed sections with adequate resolution of structural details and revealed to be an extremely useful method to study pressurized human saphenous veins.(AU)
OBJETIVO: Avaliar a inclusão em glicol metacrilato para estudar alterações morfológicas de veias safenas humanas submetidas a pressurizações breves e crescentes. MÉTODOS: Veias safena de 20 pacientes submetidos a cirurgia de revascularização do miocárdio foram distribuídas ao acaso em quatro grupos experimentais (controle, pressões de 100, 200 e 300 mmHg durante 15 segundos). Para quantificar a percentagem da superfície venosa recoberta por endotélio utilizou-se o aumento de 100x. A análise morfométrica foi realizada utilizando-se videomicroscopia com auxílio do software Leica Qwin em conjunto com um microscópio Leica e videocâmera, acoplados a um computador. RESULTADOS: Observou-se uma leve tendência de aumento quantitativo de todos os parâmetros avaliados, incluindo a percentagem de superfície recoberta por endotélio e a espessura das paredes das veias safenas. CONCLUSÕES: A inclusão em glicol metracrilato permitiu secções com adequada resolução dos detalhes estruturais, revelando-se um método extremamente útil para o estudo de veias safenas humanas pressurizadas.(AU)
Asunto(s)
Humanos , Metacrilatos , Adhesión en Plástico/métodos , Presión , Vena Safena/anatomía & histología , Túnica Íntima/ultraestructura , Microscopía por Video/métodos , Vena Safena/ultraestructuraRESUMEN
D-003 is a mixture of very-high-molecular-weight aliphatic primary acids purified from sugar-cane (Saccharum officinarum L.) wax, in which octacosanoic acid is the most abundant component. Previous experimental studies have shown that D-003 not only shows cholesterol-lowering and anti-platelet effects, but also reduces thromboxane B2 and increases prostacyclin levels. It acts by inhibiting cholesterol biosynthesis. The positioning of a non-occlusive silicone collar around the rabbit carotid artery results in the formation of a neointima. Collars were placed around the left carotid for 15 days. The contralateral artery was sham-operated. We included three experimental groups: A control group received vehicle, and two others received D-003 at 5 and 25 mg/kg until sacrificed. Samples of arteries were examined by light microscopy. To evaluate intimal thickening the cross-sectional areas of intima and media were measured. Neointima was significantly reduced in D-003-treated animals compared with controls. Furthermore, the circulating endothelial cell has been studied in this experimental model with endothelium damage. The results demonstrate the protective effect of D-003 on vascular endothelium of the studied rabbits. It is concluded that the protective effect of D-003 against neointima formation and circulating endothelial cells in this experimental model could represent potential beneficial pleiotropic effects in the anti-atherogenic profile of this substance, beyond its cholesterol-lowering and anti-platelet effects independently demonstrated.
Asunto(s)
Arterias Carótidas/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Ácidos Grasos/farmacología , Saccharum/química , Túnica Íntima/efectos de los fármacos , Animales , Arterias Carótidas/patología , Arterias Carótidas/ultraestructura , Recuento de Células , Relación Dosis-Respuesta a Droga , Células Endoteliales/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/patología , Endotelio Vascular/ultraestructura , Conejos , Distribución Aleatoria , Túnica Íntima/patología , Túnica Íntima/ultraestructura , Túnica Media/efectos de los fármacos , Túnica Media/patología , Túnica Media/ultraestructuraRESUMEN
La disfunción endotelial es precursora de aterosclerosis. La aterosclerosis subclínica puede detectarse por métodos no invasivos. Objetivos: estudiar la prevalencia de disfunción endotelial, de placas de ateroma y el espesor de íntima media en pacientes con factores de riesgo aterosclerótico en una clínica de metabolismo y prevención. Estudiar la asociación de la disfunción endotelial y el espesor de íntima media con los factores de riesgo y de la disfunción endotelial con el espesor de íntima media y las placas de ateroma. Método: se realizó un estudio prospectivo de 100 pacientes (grupo I) con múltiples factores de riesgo en prevención primaria o en prevención secundaria y de diez controles sanos (grupo II), con cero a dos factores de riesgo. Se les realizó estudio de función endotelial por vasodilatación mediada por flujo de la arteria humeral y determinación del espesor de íntima media y de placas de ateroma carotídeas. En el grupo I fueron mayores: número de factores de riesgo, prevalencia de hombres, edad y cintura. Resultados: en el grupo I la prevalencia de disfunción endotelial fue 66,0 por ciento y la vasodilatación mediada por flujo 7,4 por cientoñ4,5 por ciento, y en el grupo II 0 por ciento y 14,0 por cientooñ5,1 por ciento, respectivamente. En el grupo I el espesor de íntima media fue 0,77mmñ0,11 mm y en el grupo II fue 0,66 mmñ0,06 mm (p < 0,0001). Se asociaron a espesor de íntima media > 0,76 mm: dislipemia, presión arterial sistólica > 140 mm Hg, hipertensión y cinco o más factores de riesgo. La disfunción endotelial se asoció a espesor de íntima media > 0,82 mm (OR = 4,77, IC 95 por ciento 1,36- 16,77; p = 0,001). La prevalencia de placas de ateroma carotídeas fue 41 por ciento en el grupo I (32,5 por ciento en prevención primaria; 75 por ciento en prevención secundaria) y 0 por ciento en el grupo II (p= 0,01). La disfunción endotelial se asoció a placas de ateroma (OR 3,66, IC 95 por ciento 1,52-8,8; p = 0,0001). Conclusiones: la disfunción endotelial, el mayor espesor de íntima media y las placas de ateroma fueron frecuentes y se asociaron a la población de pacientes con múltiples factores de riesgo o en prevención secundaria o ambas situaciones. La disfunción endotelial se asoció a manifestaciones de aterosclerosis subclínica: mayor espesor de íntima media y placas de ateroma...(AU)