RESUMEN

Lower-extremity arterial disease is a major health problem with increasing prevalence, often leading to non-traumatic amputation, disability and mortality. The molecular mechanisms underpinning abnormal vascular wall remodeling are not fully understood. We hypothesized on the existence of a vascular tissue memory that may be transmitted through soluble signaling messengers, transferred from humans to healthy recipient animals, and consequently drive the recapitulation of arterial wall thickening and other vascular pathologies. We examined the effects of the intralesional infiltration for 6 days of arteriosclerotic popliteal artery-derived homogenates (100 µg of protein) into rats' full-thickness wounds granulation tissue. Animals infiltrated with normal saline solution or healthy brachial arterial tissue homogenate obtained from traumatic amputation served as controls. The significant thickening of arteriolar walls was the constant outcome in two independent experiments for animals receiving arteriosclerotic tissue homogenates. This material induced other vascular morphological changes including an endothelial cell phenotypic reprogramming that mirrored the donor's vascular histopathology. The immunohistochemical expression pattern of relevant vascular markers appeared to match between the human tissue and the corresponding recipient rats. These changes occurred within days of administration, and with no cross-species limitation. The identification of these "vascular disease drivers" may pave novel research avenues for atherosclerosis pathobiology.

Asunto(s)

Arteriosclerosis/metabolismo , Tejido de Granulación/metabolismo , Arteria Poplítea/lesiones , Proteínas/administración & dosificación , Lesiones del Sistema Vascular/inducido químicamente , Anciano , Animales , Arteriosclerosis/patología , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ratas , Lesiones del Sistema Vascular/patología

RESUMEN

Renal biopsy is useful to better understand the histological pattern of a lesion (glomerular, tubulointerstitial, and vascular) and the pathogenesis that leads to kidney failure. The potential impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the kidneys is still undetermined, and a variety of lesions are seen in the kidney tissue of coronavirus disease patients. This review is based on the morphological findings of patients described in case reports and a series of published cases. A search was conducted on MEDLINE and PubMed of case reports and case series of lesions in the presence of non-critical infection by SARS-CoV-2 published until 15/09/2020. We highlight the potential of the virus directly influencing the damage or the innate and adaptive immune response activating cytokine and procoagulant cascades, in addition to the genetic component triggering glomerular diseases, mainly collapsing focal segmental glomerulosclerosis, tubulointerstitial, and even vascular diseases. Kidney lesions caused by SARS-CoV-2 are frequent and have an impact on morbidity and mortality; thus, studies are needed to assess the morphological kidney changes and their mechanisms and may help define their spectrum and immediate or long-term impact.

Asunto(s)

Lesión Renal Aguda/patología , COVID-19/patología , Glomerulonefritis/patología , Riñón/patología , Microangiopatías Trombóticas/patología , Lesión Renal Aguda/sangre , Lesión Renal Aguda/inmunología , Inmunidad Adaptativa/inmunología , Arteriosclerosis/inmunología , Arteriosclerosis/patología , COVID-19/sangre , COVID-19/inmunología , Citocinas/inmunología , Glomerulonefritis/inmunología , Glomerulonefritis por IGA/inmunología , Glomerulonefritis por IGA/patología , Glomeruloesclerosis Focal y Segmentaria/inmunología , Glomeruloesclerosis Focal y Segmentaria/patología , Humanos , Inmunidad Innata/inmunología , Infarto/inmunología , Infarto/patología , Riñón/irrigación sanguínea , Riñón/inmunología , Necrosis de la Corteza Renal/inmunología , Necrosis de la Corteza Renal/patología , Nefritis Intersticial/inmunología , Nefritis Intersticial/patología , Nefrosis Lipoidea/inmunología , Nefrosis Lipoidea/patología , Rabdomiólisis , SARS-CoV-2 , Trombofilia/sangre , Microangiopatías Trombóticas/inmunología

RESUMEN

Objective: Intimal hyperplasia is associated with graft failure and vascular sutures in the first year after surgery and in postangioplasty restenosis. Allium sativum (common garlic) lowers cholesterol and has antioxidant effects; it also has antiplatelet and antitumor properties and, therefore, has great potential to reduce or inhibit intimal hyperplasia of the arteries. Our objective is to determine if the garlic has an efficacy to inhibit myointimal hyperplasia compared to cilostazol. Methods: Female New Zealand rabbits were divided into the following groups (n=10 each) according to treatment: group A, garlic, 800 µg×kg-1×day-1, orally; group C, cilostazol, 50 mg.day-1, orally; group PS, 10 ml of 0.9% physiological saline solution, orally. Our primary is the difference of the mean of myointimal hyperplasia. Statistical analysis was performed by using ANOVA and Tukey tests, as well as the Chi-square test. We calculated the 95% confidence interval for each point estimate, and the P value was set as < 0.05. Results: Group PS had a mean hyperplasia rate of 35.74% (95% CI, 31.76-39.71%); group C, 16.21% (95% CI, 13.36-19.05%); and group A, 21.12% (95% CI, 17.26-25.01%); P < 0.0001. Conclusion: We conclude that Allium sativum had the same efficacy in inhibiting myointimal hyperplasia when compared to the positive control, cilostazol.

Asunto(s)

Arteriosclerosis/prevención & control , Ajo/química , Tetrazoles/farmacología , Túnica Íntima/patología , Animales , Arteriosclerosis/patología , Cilostazol , Femenino , Hiperplasia/prevención & control , Inmunohistoquímica , Inhibidores de Agregación Plaquetaria , Conejos

RESUMEN

Abstract Objective: Intimal hyperplasia is associated with graft failure and vascular sutures in the first year after surgery and in postangioplasty restenosis. Allium sativum (common garlic) lowers cholesterol and has antioxidant effects; it also has antiplatelet and antitumor properties and, therefore, has great potential to reduce or inhibit intimal hyperplasia of the arteries. Our objective is to determine if the garlic has an efficacy to inhibit myointimal hyperplasia compared to cilostazol. Methods: Female New Zealand rabbits were divided into the following groups (n=10 each) according to treatment: group A, garlic, 800 µg×kg-1×day-1, orally; group C, cilostazol, 50 mg.day-1, orally; group PS, 10 ml of 0.9% physiological saline solution, orally. Our primary is the difference of the mean of myointimal hyperplasia. Statistical analysis was performed by using ANOVA and Tukey tests, as well as the Chi-square test. We calculated the 95% confidence interval for each point estimate, and the P value was set as < 0.05. Results: Group PS had a mean hyperplasia rate of 35.74% (95% CI, 31.76–39.71%); group C, 16.21% (95% CI, 13.36–19.05%); and group A, 21.12% (95% CI, 17.26–25.01%); P<0.0001. Conclusion: We conclude that Allium sativum had the same efficacy in inhibiting myointimal hyperplasia when compared to the positive control, cilostazol.

Asunto(s)

Animales , Femenino , Conejos , Arteriosclerosis/prevención & control , Tetrazoles/farmacología , Túnica Íntima/patología , Ajo/química , Arteriosclerosis/patología , Inmunohistoquímica , Inhibidores de Agregación Plaquetaria , Cilostazol , Hiperplasia/prevención & control

RESUMEN

As doenças cardiovasculares são a principal causa de mortalidade no mundo. A aterosclerose é a base fisiopatológica dessas doenças, sendo definida como um processo crônico-inflamatório multifatorial, resultando da interação de diferentes células como linfócitos, macrófagos, células endoteliais e células musculares lisas na parede arterial. A lipoproteína de baixa densidade eletronegativa [LDL(-)], uma subfração modificada da LDL nativa, desempenha um papel-chave na aterosclerose, uma vez que as modificações sofridas por esta partícula são capazes de induzir o acúmulo de ésteres de colesterol em macrófagos e a subsequente formação de células espumosas. O sistema imunológico é crucial no processo aterogênico e estratégias terapêuticas direcionadas à imunoregulação deste processo têm sido utilizadas como novas alternativas tanto na prevenção do desenvolvimento quanto da progressão desta doença. Dentre essas estratégias, destaca-se o uso de fragmentos de anticorpos como o scFv (do inglês, single chain fragment variable), que podem ainda estar conjugados a nanopartículas com o intuito de aumentar sua eficiência de ação no organismo. Diante do papel da LDL(-) na aterosclerose, este projeto objetivou avaliar os efeitos in vitro e in vivo de um sistema nanoestruturado contendo fragmentos scFv anti-LDL(-) derivatizados na superfície de nanocápsulas sobre macrófagos murinos e humanos primários e em camundongos knockout para o gene do receptor da LDL (Ldlr-/-) no desenvolvimento e na progressão dessa doença. Demonstrou-se que o tratamento de macrófagos com a formulação scFv anti-LDL(-)-MCMN-Zn diminuiu de forma significativa a captação de LDL(-), assim como a expressão de IL-1ß (mRNA e proteína) e MCP-1 (mRNA). Foi demonstrada a internalização da nanoformulação pelos macrófagos via diferentes mecanismos de endocitose, demonstrando seu potencial uso como carreador de fármacos. In vivo, a nanoformulação diminuiu de forma significativa a área da lesão aterosclerótica em camundongos Ldlr-/- submetidos à avaliação pela técnica de tomografia por emissão de pósitrons (do inglês, PET), utilizando o radiotraçador 18F-FDG (18F-desoxiglicose), associada à tomografia computadorizada (CT) com agente de contraste iodado, além da análise morfométrica das lesões no arco aórtico. O conjunto dos resultados obtidos evidenciou a ação ateroprotetora da formulação scFv anti-LDL(-)-MCMN-Zn, reforçando seu potencial como estratégia terapêutica na aterosclerose

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Cardiovascular diseases are the leading cause of mortality worldwide. Atherosclerosis is the pathophysiological basis of these diseases, defined as a chronic inflammatory multifactorial process, resulting from the interaction of several cells such as lymphocytes macrophages, endothelial cells and smooth muscle cells within the arterial wall. The electronegative low-density lipoprotein [LDL(-)], a modified subfraction of native LDL, plays a key role in atherosclerosis, since its modifications are capable of inducing the accumulation of cholesteryl esters in macrophages and the subsequent foam cells formation. The immune system is crucial in atherogenic process and therapeutic strategies directed to the immunoregulation of this process have been used as a new alternative in the prevention of the development as well as the progression of this disease. Among these strategies, it is the use of antibody fragments such as scFv (single chain fragment variable), which may be also conjugated to nanoparticles in order to increase their efficiency in the body. Given the role of LDL(-) in atherosclerosis, the aim of this project was to evaluate the in vitro and in vivo effects of a nanostructured system containing scFv anti-LDL(-) fragments derivatized on the surface of nanocapsules on murine and human primary macrophages and in the development and progression of the disease in LDL receptor knockout mice (Ldlr-/-). It was demonstrated that the treatment of macrophages with scFv anti-LDL(-)-MCMN-Zn formulation significantly decreases the uptake of LDL(-) and the expression IL-1ß (mRNA and protein) and MCP-1 (mRNA). Moreover, the internalization of the nanoformulation by macrophages through different endocytosis mechanisms was shown, demonstrating its potential use as a nanocarrier. In vivo, the nanoformulation decreased the area of atherosclerotic lesions in Ldlr-/- mice evaluated by positron emission tomography with 18F-FDG associated with computed tomography with iodinated contrast agent (PET/CT), besides the lesion morphometric analysis at the aortic arch Thus, these data provide evidence of the atheroprotection action of the ateroprotection action of the scFv anti-LDL(-)-MCMN-Zn formulation, suggesting its promising use as a therapeutic strategy for atherosclerosis

Asunto(s)

Animales , Masculino , Arteriosclerosis/patología , Nanocápsulas , Anticuerpos de Cadena Única/análisis , Microscopía Confocal/instrumentación , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/análisis , Citometría de Flujo/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos

RESUMEN

Increased lifespan in the last few decades has substantially changed the scenario for renal artery stenosis. Indeed, because older populations show a higher prevalence of atherosclerotic disease, the incidence of atheromatous renal artery stenosis has also increased. Intuitively, one could surmise that stenosis removal should void both the hypertension and the kidney damage resulting from the obstructive stenosis. Surprisingly, a number of important clinical trials have failed to show the reversion seen in experimental models. The reasons for these differences may be linked to chronicity and inflammation associated with the atherosclerotic lesion. However, the failure to obtain a favorable response may also be related to abnormalities in the contralateral kidney. Indeed, this apparently normal kidney should work to compensate the hemodynamic effects of the ipsilateral stenosed kidney. Instead, structure and function in the contralateral kidney can be altered in renal artery stenosis to the point that this nonstenotic kidney may sustain both, hypertension and progressive kidney disease. Certainly, comparing the effects of clip removal in the Goldblatt model to angioplasty in clinical settings with atherosclerotic lesions may be totally inappropriate. Nevertheless, there remain certain clinical situations such as bilateral renal arterial disease, congestive heart failure, and progressive renal failure, where angioplasty may be an alternative. These approaches however are yet to be tested.

Asunto(s)

Arteriosclerosis/terapia , Hipertensión/etiología , Obstrucción de la Arteria Renal/terapia , Angioplastia/métodos , Animales , Arteriosclerosis/complicaciones , Arteriosclerosis/patología , Progresión de la Enfermedad , Humanos , Hipertensión/terapia , Incidencia , Enfermedades Renales/etiología , Enfermedades Renales/terapia , Prevalencia , Obstrucción de la Arteria Renal/complicaciones , Obstrucción de la Arteria Renal/fisiopatología

RESUMEN

Estudo qualitativo e descritivo, cujo objetivo foi identificar e analisar as representações sociais de educação em saúde à pessoa vivendo com HIV entre profissionais de saúde. Os cenários foram três serviços de atenção à DST/HIV/AIDS, em Belém-PA, Brasil, e 37 profissionais de saúde participaram da pesquisa. A coleta de dados deu-se em 2012-2013 por meio de entrevista em profundidade; a análise utilizou o software Alceste 4.10. Com base no conjunto dos resultados foi possível vislumbrar que a educação em saúde pode ser compreendida a partir de categorias: a configuração do agir educativo; as condições sine qua non: educação no trabalho e estrutura da unidade; o processo pedagógico. Conclui-se que as representações sociais configuram-se como orientação-informação para precaução-prevenção e revelam-se no movimento do agir persistente ao emergente, o que suscita uma educação em saúde permanente para se chegar à integralidade nos serviços.

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This is a qualitative and descriptive study, which aimed at identifying and analyzing social representations of health education to HIV patients among health professionals. The setting included three healthcare DST/HIV/AIDS services in Belém-PA, Brazil, and 37 health professionals participated in the study. Data collection was conducted in 2012-2013 on the basis of in-depth interviews and analysis was made on Alceste 4.0 software. Final results indicated that health education can be comprehended in light of categories: educational action; sine qua non: education and training at work, and unit structure; teaching-learning process. Conclusions show that social representations are set as guidance-information for precaution-prevention and that they come forth along continuous and emerging action flow, bringing about permanent health education to ensure healthcare services in full.

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Estudio cualitativo y descriptivo, que objetivó identificar y analizar las representaciones sociales de educación en salud a la persona viviendo con HIV entre profesionales de salud. Los escenarios fueron tres servicios de atendimiento al DST/HIV/ SIDA, en Belém-PA, Brasil, y 37 profesionales de salud participaran del estudio. La colecta de datos se dio en 2012-2013, por medio de entrevista en profundidad y el análisis utilizo el software Alceste 4.10. Con base en el conjunto de los resultados fue posible vislumbrar que la educación en salud puede ser comprendida a partir de categorías: la configuración del acto educativo; las condiciones sine qua non: educación en el trabajo y estructura de la unidad; el proceso pedagógico. Se concluye que las representaciones sociales se configuran como orientación-información para precaución-prevención y se revelan en el movimiento del acto persistente al emergente, lo que suscita una educación en salud permanente para llegarse a la integralidad en los servicios.

Asunto(s)

Humanos , Animales , Masculino , Femenino , Conejos , Antioxidantes/administración & dosificación , Arteriosclerosis/tratamiento farmacológico , Probucol/administración & dosificación , Ubiquinona/administración & dosificación , Ubiquinona/análogos & derivados , alfa-Tocoferol/administración & dosificación , Antioxidantes/farmacocinética , Aorta/metabolismo , Aorta/patología , Arteriosclerosis/metabolismo , Arteriosclerosis/patología , Coenzimas , Modelos Animales de Enfermedad , Lípidos/sangre , Lipoproteínas LDL/metabolismo , Probucol/farmacocinética , Ubiquinona/metabolismo , Ubiquinona/farmacocinética , Vitamina E/metabolismo , alfa-Tocoferol/farmacocinética

RESUMEN

It is generally accepted that Alois Alzheimer, the German neuropathologist and clinician, discovered the disease that carries his name, after the clinicopathological study of a 51-year-old woman named Auguste D. who presented a dementia syndrome. The pathological study of the brain revealed the presence of neurofibrillary tangles and senile plaques. Emil Kraepelin coined the eponym Alzheimer's disease in the 8th edition of his textbook Clinical Psychiatry. However, several critical aspects of this history have been pointed out by historians of psychiatry. This article provides a narrative of the best-known facts leading to the formation of the original concept but also presents an informed discussion of the main critical points: 1. The descriptions of senile plaques and neurofibrillary tangles in the context of dementia before Alzheimer's report. 2. The presence or absence of arteriosclerotic changes in the brain of Auguste D. 3. The presence of noncognitive symptoms in August D. 4. The influence of social, political and economic issues in the formation and selection of medical concepts.

Asunto(s)

Enfermedad de Alzheimer/historia , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/fisiopatología , Arteriosclerosis/complicaciones , Arteriosclerosis/patología , Encéfalo/patología , Demencia/historia , Demencia/patología , Demencia/fisiopatología , Epónimos , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Ovillos Neurofibrilares/patología , Placa Amiloide/patología

Asunto(s)

Trasplante de Riñón/patología , Riñón/patología , Lupus Eritematoso Sistémico/complicaciones , Enfermedades Renales Poliquísticas/patología , Adulto , Arteriosclerosis/patología , Bacteriemia/microbiología , Catéteres de Permanencia , Enterococcus faecium , Resultado Fatal , Humanos , Masculino , Enfermedades Renales Poliquísticas/terapia , Diálisis Renal/efectos adversos , Bazo/patología

RESUMEN

BACKGROUND: Carotid intima media thickness (CIMT) is a marker of cardiovascular damage that can be modified by traditional risk factors. AIM: To determine attributable risk factors for a high CIMT among healthy adults. MATERIAL AND METHODS: A sample of 1270 individuals (636 males and 634 females) aged 44 ± 11 years, was studied. Blood pressure, weight, height, lipid profile and blood glucose were measured in all. CIMT and the presence of atherosclerotic plaques were determined by carotid ultrasound. Standard criteria were used to define hypertension, dyslipidemia and diabetes. RESULTS: Mean CIMT in the sample studied was 0.62 ± 0.01 mm and percentile 75 was 0.67. The most important risk factor for a CIMT over percentile 75 and the presence of atherosclerotic plaques was hypertension with attributable risks of 54 and 57%, respectively. CONCLUSIONS: In this sample, the main risk factor for a high CIMT was hypertension.

Asunto(s)

Arteriosclerosis/patología , Enfermedades de las Arterias Carótidas/patología , Grosor Intima-Media Carotídeo , Adulto , Anciano , Arteriosclerosis/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores Socioeconómicos

RESUMEN

Background: Carotid intima media thickness (CIMT) is a marker of cardiovascular damage that can be modified by traditional risk factors. Aim: To determine attributable risk factors for a high CIMT among healthy adults. Material ana Methods: A sample of 1270 individuáis (636 males and 634 femóles) aged 44 ±11 years, was studied. Blood pressure, weight, height, lipidprofile and blood glucose were measured in all. CIMT and thepresence of atheroscleroticplaques were determined by carotid ultrasound. Standard criteria were used to define hypertension, dyslipidemia and diabetes. Results: Mean CIMT in the sample studied was 0.62 ± 0.01 mm and percentile 75 was 0.67. The most important risk factor for a CIMT over percentile 75 and thepresence of atherosclerotic plaques was hypertension with attributable risks of 54 and 57 percent, respectively. Conclusions: In this sample, the main risk factor for a high CIMT was hypertension.

Asunto(s)

Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arteriosclerosis/patología , Enfermedades de las Arterias Carótidas/patología , Grosor Intima-Media Carotídeo , Arteriosclerosis , Enfermedades de las Arterias Carótidas , Estudios Transversales , Factores de Riesgo , Factores Socioeconómicos

RESUMEN

This review provides examples of the fact that different procedures for the measurement of atherosclerosis in mice may lead to interpretation of the extent of atherosclerosis having markedly different biological and clinical significance for humans: 1) aortic cholesterol measurement is highly sensitive for the detection of early and advanced atherosclerosis lesions, but misses the identification of the location and complexity of these lesions that are so critical for humans; 2) the histological analysis of the aortic root lesions in simvastatin-treated and control mice reveals similar lesion morphology in spite of the remarkable simvastatin-induced reduction of the aortic cholesteryl ester content; 3) in histological analyses, chemical fixation and inclusion may extract the tissue fat and also shrink and distort tissue structures. Thus, the method may be less sensitive for the detection of slight differences among the experimental groups, unless a more suitable procedure employing physical fixation with histological sample freezing using optimal cutting temperature and liquid nitrogen is employed. Thus, when measuring experimental atherosclerosis in mice, investigators should be aware of several previously unreported pitfalls regarding the extent, location and complexity of the arterial lesion that may not be suitable for extrapolation to human pathology.

Asunto(s)

Animales , Humanos , Ratones , Aorta/patología , Arteriosclerosis/patología , Colesterol/análisis , Modelos Animales de Enfermedad , Anticolesterolemiantes/uso terapéutico , Aorta/química , Arteriosclerosis/tratamiento farmacológico , Simvastatina/uso terapéutico , Túnica Íntima/química , Túnica Íntima/patología

RESUMEN

This review provides examples of the fact that different procedures for the measurement of atherosclerosis in mice may lead to interpretation of the extent of atherosclerosis having markedly different biological and clinical significance for humans: 1) aortic cholesterol measurement is highly sensitive for the detection of early and advanced atherosclerosis lesions, but misses the identification of the location and complexity of these lesions that are so critical for humans; 2) the histological analysis of the aortic root lesions in simvastatin-treated and control mice reveals similar lesion morphology in spite of the remarkable simvastatin-induced reduction of the aortic cholesteryl ester content; 3) in histological analyses, chemical fixation and inclusion may extract the tissue fat and also shrink and distort tissue structures. Thus, the method may be less sensitive for the detection of slight differences among the experimental groups, unless a more suitable procedure employing physical fixation with histological sample freezing using optimal cutting temperature and liquid nitrogen is employed. Thus, when measuring experimental atherosclerosis in mice, investigators should be aware of several previously unreported pitfalls regarding the extent, location and complexity of the arterial lesion that may not be suitable for extrapolation to human pathology.

Asunto(s)

Aorta/patología , Arteriosclerosis/patología , Colesterol/análisis , Modelos Animales de Enfermedad , Animales , Anticolesterolemiantes/uso terapéutico , Aorta/química , Arteriosclerosis/tratamiento farmacológico , Humanos , Ratones , Simvastatina/uso terapéutico , Túnica Íntima/química , Túnica Íntima/patología

RESUMEN

Lípides nitrados (NO₂-FA) são apontados como uma nova classe de mediadores lipídicos, podendo atuar como reservatórios endógenos de Oxido nítrico (^.NO) bem como moduladores pluripotentes de sinalização celular. Recentemente, tem sido sugerido que os doadores de ^.NO estariam envolvidos na regulação da angiogênese. Evidências contundentes indicam ainda que o processo de neovascularização poderia contribuir para a patogênese de uma serie de condições clínicas, entre elas a aterosclerose. Contudo, apesar de diversos estudos terem explorado os efeitos biológicos dos NO₂-FA, os efeitos destes compostos sobre o processo de angiogênese não haviam sido descritos. Dessa maneira, o presente trabalho investigou os efeitos dos NO₂-FA (derivados da nitração do acido linoléico e oléico) no processo de angiogênese. Demonstrou-se que os NO₂-FA podem atuar como mediadores pro-angiogênicos. Este efeito foi caracterizado em células endoteliais humanas, assim como, em modelos ex vivo e in vivo. Nas células endoteliais, observou-se que os NO₂-FA não influenciaram a proliferação ou a viabilidade celular, ao passo que estimularam a migração. Demonstrou-se também que os NO₂-FA podem modular o brotamento ex vivo de novos vasos, em cultura de anéis de aorta de rato, bem como o processo angiogênico in vivo observado na membrana corioalantóica de embrião de galinha. Adicionalmente, os NO₂-FA induziram a expressão do fator de crescimento endotelial vascular (VEGF), que é o principal mediador do processo de angiogênese. Em relação ao mecanismo de ação, os achados sugerem que os efeitos demonstrados seriam via mecanismos dependentes de ^.NO, uma vez que foram abolidos na presença de um seqüestrador de ^.NO, enquanto concentrações equivalentes dos Lípides precursores não demonstraram qualquer influência nas condições experimentais utilizadas neste estudo...

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Nitrated lipids ( NO₂-FA) are described as a new class of lipid mediators that are able to act as endogenously nitric oxide ( ^.NO) reservoirs as well as pluripotent cell signaling modulators. Furthermore, recent findings suggest that ^.NO donors could be involved in the regulation of angiogenesis. Compelling evidence also indicate that the neovascularization process might contribute to the pathogenesis of many clinical conditions, such as atherosclerosis. However, although several studies have explored the NO₂-FA biological properties, the effects of these compounds on the angiogenic process remain unknown. Hence, the present study investigated the effects of the NO₂-FA (derivates from the nitration of linoleic and oleic acids at physiological concentrations) on angiogenesis process. It is demonstrated that the NO2-FA could act as pro-angiogenic mediators. This effect was observed not only in human endothelial cells but also in ex vivo and in vivo models. Using endothelial cells, it is showed that NO₂-FA failed to affect cell proliferation or influence cellular viability, but significantly stimulated cell migration. It was also found that the NO₂-FA might modulate the ex vivo sprouting of new vessels as well as the in vivo angiogenic process, while inducing the expression of the vascular endothelial growth factor, the main mediator of angiogenesis. The data are consistent with the hypothesis that the observed effects mediated by NO-dependent mechanisms, since the presence of a ^.NO scavenger abrogated the induced effects, whereas equimolar concentrations of its precursors, showed no effect on angiogenesis under our experimental conditions. Finally, the pro-angiogenic effects of NO2-FA were mediated by the stabilization of the hypoxia inducible factor-l1á (HIF-1á) protein, because these compounds increased the protein amount and failed to show inductive effects...

Asunto(s)

Humanos , Animales , Bovinos , Embrión de Pollo , Moduladores de la Angiogénesis/análisis , Arteriosclerosis/patología , Lípidos/química , Nitratos/síntesis química , Movimiento Celular , Cromatografía Liquida , Células Endoteliales , Expresión Génica , Espectrometría de Masas , Reacciones Bioquímicas/análisis

RESUMEN

OBJECTIVE: 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%) 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% stenosis in 57% (vs. 56% in nondiabetic) of the anterior tibial; 78% (vs. 68%) of the posterior tibial; 58% (vs. 50%) 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% vs. 23%). CONCLUSIONS: There were no differences in histological characteristics of atherosclerosis between the two groups. Capillary thickening has been more observed in diabetics.

Asunto(s)

Amputación Quirúrgica/efectos adversos , Arteriosclerosis/patología , Angiopatías Diabéticas/cirugía , Extremidad Inferior/irrigación sanguínea , Anciano , Análisis de Varianza , Arteriolas , Capilares , Distribución de Chi-Cuadrado , Femenino , Humanos , Pierna/irrigación sanguínea , Extremidad Inferior/patología , Masculino , Persona de Mediana Edad , Factores Sexuales

RESUMEN

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.

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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.

Asunto(s)

Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Amputación Quirúrgica/efectos adversos , Arteriosclerosis/patología , Angiopatías Diabéticas/cirugía , Extremidad Inferior/irrigación sanguínea , Análisis de Varianza , Arteriolas , Capilares , Distribución de Chi-Cuadrado , Pierna/irrigación sanguínea , Extremidad Inferior/patología , Factores Sexuales

RESUMEN

OBJECTIVE: To describe and test a practical protocol to measure common carotid intima-media thickness that uses the combined values of two longitudinal examination angles to increase sensitivity. METHOD: Between February and September 2005, 206 patients underwent duplex scan examination of carotid vessels, and the intima-media thickness of 407 common carotids were measured in three angles: transversal, longitudinal posterolateral, and anterolateral, with three intima-media thickness measurements for each near and far wall. In addition to numbers obtained from the three angles of measurement, a fourth visual perspective was obtained by combining the intima-media thickness results of posterolateral and anterolateral longitudinal views and considering the thickest wall measurement. RESULTS: Two hundred seventy (66.3%) carotid arteries had an intima-media thickness thicker than 1mm. The mean intima-media thickness values achieved by the different incidences were 1.26+/-0.6 mm (transversal), 1.17+/-0.54 mm (longitudinal anterolateral), and 1.18+/-0.58 mm (longitudinal posterolateral). A significant difference in intima-media thickness measurement values was observed when the three angles of examination plus the combined positive results of both longitudinal angles were compared by ANOVA (P=0.005). The LSD Post-Hoc test determined that the combined longitudinal view results were similar to the transversal views (P=0.28) and had greater intima-media thickness means than isolated anterolateral or posterolateral longitudinal views (P=0.02 and 0.05, respectively). CONCLUSIONS: The protocol presented is a practical method for obtaining common carotid artery intima-media thickness measurements. The combined longitudinal posterolateral and anterolateral longitudinal views provide a more sensitive evaluation of the inner layers of the carotid walls than isolated longitudinal views.

Asunto(s)

Arteriosclerosis/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Arteria Carótida Común/diagnóstico por imagen , Túnica Íntima/diagnóstico por imagen , Túnica Media/diagnóstico por imagen , Adulto , Arteriosclerosis/patología , Enfermedades de las Arterias Carótidas/patología , Arteria Carótida Común/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Factores de Tiempo , Túnica Íntima/patología , Túnica Media/patología , Ultrasonografía Doppler Dúplex

RESUMEN

OBJECTIVE: To describe and test a practical protocol to measure common carotid intima-media thickness that uses the combined values of two longitudinal examination angles to increase sensitivity. METHOD: Between February and September 2005, 206 patients underwent duplex scan examination of carotid vessels, and the intima-media thickness of 407 common carotids were measured in three angles: transversal, longitudinal posterolateral, and anterolateral, with three intima-media thickness measurements for each near and far wall. In addition to numbers obtained from the three angles of measurement, a fourth visual perspective was obtained by combining the intima-media thickness results of posterolateral and anterolateral longitudinal views and considering the thickest wall measurement. RESULTS: Two hundred seventy (66.3 percent) carotid arteries had an intima-media thickness thicker than 1mm. The mean intima-media thickness values achieved by the different incidences were 1.26±0.6mm (transversal), 1.17±0.54mm (longitudinal anterolateral), and 1.18±0.58mm (longitudinal posterolateral). A significant difference in intima-media thickness measurement values was observed when the three angles of examination plus the combined positive results of both longitudinal angles were compared by ANOVA (P=0.005). The LSD Post-Hoc test determined that the combined longitudinal view results were similar to the transversal views (P=0.28) and had greater intima-media thickness means than isolated anterolateral or posterolateral longitudinal views (P=0.02 and 0.05, respectively). CONCLUSIONS: The protocol presented is a practical method for obtaining common carotid artery intima-media thickness measurements. The combined longitudinal posterolateral and anterolateral longitudinal views provide a more sensitive evaluation of the inner layers of the carotid walls than isolated longitudinal views.

Asunto(s)

Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arteriosclerosis , Enfermedades de las Arterias Carótidas , Arteria Carótida Común , Túnica Íntima , Túnica Media , Arteriosclerosis/patología , Enfermedades de las Arterias Carótidas/patología , Arteria Carótida Común/patología , Sensibilidad y Especificidad , Factores de Tiempo , Túnica Íntima/patología , Túnica Media/patología , Ultrasonografía Doppler Dúplex

RESUMEN

OBJECTIVE: Atherosclerotic inflammation with a possible role of infectious agents can contribute to the pathogenesis of abdominal aortic aneurysms (AAA). The finding of Chlamydia pneumoniae (CP) in these lesions in previous non-quantifying studies ranged from 0-100%. The objective is to quantify the presence of CP and Mycoplasma pneumoniae (MP) in AAA. METHODS: The thickness, and the number of cells positive for CP detected by the immunohistochemistry (immunoperoxidase, which is a type of immunohistochemical stain used in molecular biology, medical research, and clinical diagnostics), and the percentage of the area occupied by the Mycoplasma pneumoniae detected by in situ hybridization in three layers of the aorta were measured using an image-analysis system in 10 necropsies of abdominal aneurysmatic aortas. Three groups were used as controls: 1) samples of the same aortas, outside the aneurysms, except if the dilatation took the whole sub-renal portion of the artery (n=7); 2) aortas with severe atherosclerosis but without aneurysms (n=10); 3) aortas without or with mild atherosclerosis (n=10). All specimens were obtained at necropsies. Wald's test was used to compare groups; significance level was established at 5%. RESULTS: The tunica intima was thinner and the tunica media was thicker in the normal cases than in the other groups (p<0.01). Positive cells for CP were found in all groups, more frequently at the adventitia; no significant difference was detected between the groups (p>0.05). MP was also detected in all groups. This agent predominated in the group of patients with atherosclerosis, but without aneurysms at both tunica intima and adventitia; nevertheless, there were no significant differences between the groups (p>0.05). CONCLUSIONS: Our data suggested that the bacteria we focused to, does not play an important role in the pathogenesis of AAA.

Asunto(s)

Aneurisma de la Aorta Abdominal/microbiología , Arteriosclerosis/microbiología , Chlamydophila pneumoniae/aislamiento & purificación , Mycoplasma pneumoniae/aislamiento & purificación , Anciano , Anciano de 80 o más Años , Aorta Abdominal/microbiología , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/patología , Arteriosclerosis/patología , Estudios de Casos y Controles , Tejido Conectivo/microbiología , Tejido Conectivo/patología , Estudios Transversales , Femenino , Humanos , Inmunohistoquímica/métodos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Túnica Íntima/microbiología , Túnica Íntima/patología , Túnica Media/microbiología , Túnica Media/patología

RESUMEN

Evidencia reciente confirma que la enfermedad cardiovascular se inicia en la infancia, y la dislipidemia es uno de los principales factores de riesgo asociados. La detección precoz de la hipercolesterolemia en niños con factores de riesgo, previene la morbimortalidad cardiovascular en el adulto. Se propone un esquema de detección y manejo de la dislipidemia, basado en la experiencia de grupos de expertos, así como medidas dietéticas y terapéuticas a seguir. Se debe hacer hincapié en cambios de estilo de vida a largo plazo, recomendando hábitos alimentarios saludables y ejercicio ya que la obesidad es la causa mas frecuente de dislipidemia en el niño. Existen varias alternativas farmacológicas, y en su uso y selección se debe evaluar el riesgo en forma individual, tomando en cuenta la edad, los niveles séricos de lípidos, la magnitud y el número de eventos cardiovasculares en familiares y los posibles efectos secundarios. Actualmente las estatinas están tomando un papel importante en el tratamiento de la hipercolesterolemia familiar en niños sin embargo se requieren más estudios a fin de establecer su seguridad en este grupo de edad. En vista que la hipercolesterolemia es un factor de riesgo modificable y determinante en la enfermedad cardiovascular, todas las intervenciones que se puedan hacer en la niñez, ofrecen una oportunidad de prevención.

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Recent evidence corroborate that cardiovascular disease begins in childhood and that hyperlipidemia is one of the main associated risk factors. Early screening of hypercholesterolemia in high risk children should be performed in order to prevent cardiovascular morbidity and mortality in adulthood. An approach for detection and management of hypercholesterolemia is proposed with dietary and therapeutic strategies based on the experience of expert groups. Since obesity is the most common cause of hyperlipidemia in children, special emphasis should be made in long lasting lifestyle changes. Treatment always must include dietary modifications and exercise. Several pharmacologic alternatives are available, and when deciding its use, the child's risk must be individually analyzed, considering age, type and degree of dyslipidemia, and possible adverse effects. Since hypercholesterolemia is a modifiable and determinant risk in cardiovascular disease, all interventions done in childhood offer the opportunity of cardiovascular disease prevention in adulthood.

Asunto(s)

Humanos , Masculino , Femenino , Niño , Adolescente , Arteriosclerosis/patología , Dislipidemias/metabolismo , Dislipidemias/patología , Dislipidemias/terapia , Enfermedades Cardiovasculares/etiología , Hipercolesterolemia/terapia , Enfermedades Vasculares/fisiopatología , Obesidad/prevención & control , Pediatría