Endothelium-restricted endothelin-1 overexpression in type 1 diabetes worsens atherosclerosis and immune cell infiltration via NOX1.

AIMS: NADPH oxidase (NOX) 1 but not NOX4-dependent oxidative stress plays a role in diabetic vascular disease, including atherosclerosis. Endothelin (ET)-1 has been implicated in diabetes-induced vascular complications. We showed that crossing mice overexpressing human ET-1 selectively in endothelium (eET-1) with apolipoprotein E knockout (Apoe-/-) mice enhanced high-fat diet-induced atherosclerosis in part by increasing oxidative stress. We tested the hypothesis that ET-1 overexpression in the endothelium would worsen atherosclerosis in type 1 diabetes through a mechanism involving NOX1 but not NOX4. METHODS AND RESULTS: Six-week-old male Apoe-/- and eET-1/Apoe-/- mice with or without Nox1 (Nox1-/y) or Nox4 knockout (Nox4-/-) were injected intraperitoneally with either vehicle or streptozotocin (55 mg/kg/day) for 5 days to induce type 1 diabetes and were studied 14 weeks later. ET-1 overexpression increased 2.5-fold and five-fold the atherosclerotic lesion area in the aortic sinus and arch of diabetic Apoe-/- mice, respectively. Deletion of Nox1 reduced aortic arch plaque size by 60%; in contrast, Nox4 knockout increased lesion size by 1.5-fold. ET-1 overexpression decreased aortic sinus and arch plaque alpha smooth muscle cell content by ∼35% and ∼50%, respectively, which was blunted by Nox1 but not Nox4 knockout. Reactive oxygen species production was increased two-fold in aortic arch perivascular fat of diabetic eET-1/Apoe-/- and eET-1/Apoe-/-/Nox4-/- mice but not eET-1/Apoe-/-/Nox1y/- mice. ET-1 overexpression enhanced monocyte/macrophage and CD3+ T-cell infiltration ∼2.7-fold in the aortic arch perivascular fat of diabetic Apoe-/- mice. Both Nox1 and Nox4 knockout blunted CD3+ T-cell infiltration whereas only Nox1 knockout prevented the monocyte/macrophage infiltration in diabetic eET-1/Apoe-/- mice. CONCLUSION: Endothelium ET-1 overexpression enhances the progression of atherosclerosis in type 1 diabetes, perivascular oxidative stress, and inflammation through NOX1.

Potential Role of Endothelin in Early Vascular Aging.

Early vascular aging is a process associated with gradual alterations in the vessels, regarding their structure and function, taking a more rapid course than normal biological aging in the arteries. In the presence of cardiovascular disease, these age-associated alterations are accelerated, contributing in the appearance or the progression of cardiovascular disease, such as high blood pressure, dyslipidemia, smoking and diabetes. Endothelin-1 (ET-1) is the most abundant and important endothelin produced by vascular cells. ET-1 exerts its biological actions through the activation of two receptors: ETA and ETB. Many important functions are mediated by the activation of these receptors, such as cardiovascular remodeling, vasoconstriction, cell proliferation and differentiation, production of extracellular matrix, and water and sodium secretion control. ETA receptor seems to participate in the pathogenesis and development of diseases, such as diabetes, atherosclerosis, systemic and pulmonary hypertension, and cardiac remodeling after myocardial ischemia, whereas ETB receptor seems to prevent the overstimulation of ETA receptor, acting as a clearance receptor. Increased ET-1 system activity may contribute to vascular dysfunction in aging via multiple pathways, such as direct hemodynamic effects, vascular oxidative stress, inflammatory activity, mitogenic stimulation of the vascular smooth muscle cells and fibrotic processes. Endothelin receptor antagonists were considered to be used for the treatment of some diseases like hypertension, diabetes and chronic kidney disease. However, besides pulmonary hypertension, this class is not in clinical use because of the side effects and the availability of safer drugs for the treatment of these diseases.

Alterações cardiometabólicas em mulheres hipertensas com obesidade abdominal / Cardiometabolic disorders in Hypertensive women with abdominal obesity

Fundamentos: Estudos mostram o aumento da circunferência abdominal como indicador relevante de riscocardiovascular (RCV) aumentado.Objetivo: Identificar alterações cardíacas estruturais e funcionais em mulheres hipertensas não diabéticas comobesidade abdominal (OA). Métodos: Estudo transversal com 120 mulheres hipertensas, de 40-65 anos, estratificadas em: grupo sem obesidadeabdominal (SOA, n=42) e com obesidade abdominal (COA, n=78), sendo circunferência abdominal < ou ≥88 cm, respectivamente. Realizou-se avaliação clínica, exames bioquímicos, ecoDopplercardiograma e ultrassonografia de carótida.Resultados: A média de idade foi 53±1 anos nos grupos. A pressão arterial (PA) sistólica, embora maior no grupo COA, não atingiu significância estatística (145±2mmHg vs. 140±2mmHg, p=0,098). Grupo COA apresentou maiorPA diastólica (90±1mmHg vs. 85±1mmHg, p <0,05), maior número de critérios (3,1±0,1 vs. 1,4±0,1, p<0,001) e prevalência de síndrome metabólica (62,8% vs. 11,9%, p<0,001). Apesar de glicemias normais, pacientes COA apresentaram índices mais altos de HOMA-IR (2,62±0,22 vs. 1,61±0,17 p<0,01) e HOMA-beta (358±57 vs. 200±22, p<0,05). Na avaliação ecocardiográfica, a função sistólica foi semelhante nos grupos, mas o grupo COA apresentou evidências de disfunção diastólica pelo Doppler tissular e prevalência maior de hipertrofia ventricular esquerda (29,2% vs. 2,4%), sem diferença entre a espessura médio-intimal da carótida.Conclusões: Nesta amostra de hipertensas não diabéticas, a obesidade abdominal foi associada com maiores níveis de pressão arterial diastólica, redução da sensibilidade à insulina e alterações cardíacas, especialmente hipertrofia ventricular esquerda e disfunção diastólica. Contudo, não houve evidência de aterosclerose carotídea subclínica nas hipertensas com e sem obesidade abdominal.

Background: Studies show increased waist circumference as a relevant indicator of increased cardiovascular risk (CVR). Objective: To identify structural and functional cardiac abnormalities in nondiabetic hypertensive women with abdominal obesity (AO). Methods: Cross-sectional study with 120 hypertensive women, aged 40-65, stratified into: group with no abdominal obesity (NAO,n=42) and with abdominal obesity (QAO, n=78), and waist circumference < or ≥88cm, respectively. Clinical evaluation, biochemical tests, Doppler echocardiography and carotid ultrasound were conducted. Results: Average age was 53±1 in the groups. Although the systolic blood pressure (BP) was higher in the WAO group, it did not reach statistical significance (145±2mmHg vs. 140±2mmHg, p=0.098). The WAO group had higher diastolic BP (90±1mmHg vs. 85±1mmHg, p<0.05), greater number of criteria (3.1±0.1 vs. 1.4±0.1, p<0.001) and prevalence of metabolic syndrome (62.8% vs.11.9%; p<0.001). Despite normal blood glucose levels, WAO patients had higher HOMA-IR levels (2.62±0.22 vs. 1.61±0.17 p<0.01) and HOMA-beta levels (358±57 vs. 200±22, p<0.05). In the echocardiographic evaluation, systolic function was similar in bothgroups, but the WAO group presented evidence of diastolic dysfunction by tissue Doppler and higher prevalence of left ventricular hypertrophy (29.2% vs. 2.4%), with no difference between the carotid artery intima-media thickness.Conclusions: In this sample of nondiabetic hypertensive women, abdominal obesity was associated with higher levels of diastolic blood pressure, reduced insulin sensitivity and cardiac issues, especially left ventricular hypertrophy and diastolic dysfunction.However, there was no evidence of subclinical carotid atherosclerosis in hypertensive patients with and without abdominal obesity.

Cost-effectiveness analysis of medical treatment of benign prostatic hyperplasia in the Brazilian public health system.

OBJECTIVE: To perform a cost-effectiveness analysis of medical treatment of benign prostatic hyperplasia (BPH) under Brazilian public health system perspective (Unified Health System--"Sistema Unico de Saude (SUS)"). MATERIAL AND METHODS: A revision of the literature of the medical treatment of BPH using alpha-blockers, 5-alpha-reductase inhibitors and combinations was carried out. A panel of specialists defined the use of public health resources during episodes of acute urinary retention (AUR), the treatment and the evolution of these patients in public hospitals. A model of economic analysis (Markov) predicted the number of episodes of AUR and surgeries (open prostatectomy and transurethral resection of the prostate) related to BPH according to stages of evolution of the disease. Brazilian currency was converted to American dollars according to the theory of Purchasing Power Parity (PPP 2010: US$ 1 = R$ 1.70). RESULTS: The use of finasteride reduced 59.6% of AUR episodes and 57.9% the need of surgery compared to placebo, in a period of six years and taking into account a treatment discontinuity rate of 34%. The mean cost of treatment was R$ 764.11 (US$ 449.78) and R$ 579.57 (US$ 340.92) per patient in the finasteride and placebo groups, respectively. The incremental cost-effectiveness ratio (ICERs) was R$ 4.130 (US$ 2.429) per episode of AUR avoided and R$ 2.735 (US$ 1.609) per episode of surgery avoided. The comparison of finasteride + doxazosine to placebo showed a reduction of 75.7% of AUR episodes and 66.8% of surgeries in a 4 year time horizon, with a ICERs of R$ 21.191 (US$ 12.918) per AUR episodes avoided and R$ 11.980 (US$ 7.047) per surgery avoided. In the sensitivity analysis the adhesion rate to treatment and the cost of finasteride were the main variables that influenced the results. CONCLUSIONS: These findings suggest that the treatment of BPH with finasteride is cost-effective compared to placebo in the Brazilian public health system perspective.

Cost-effectiveness analysis of medical treatment of benign prostatic hyperplasia in the Brazilian public health system

OBJECTIVE: To perform a cost-effectiveness analysis of medical treatment of benign prostatic hyperplasia (BPH) under Brazilian public health system perspective (Unified Health System - "Sistema Único de Saúde (SUS)"). MATERIAL AND METHODS: A revision of the literature of the medical treatment of BPH using alpha-blockers, 5-alpha-reductase inhibitors and combinations was carried out. A panel of specialists defined the use of public health resources during episodes of acute urinary retention (AUR), the treatment and the evolution of these patients in public hospitals. A model of economic analysis(Markov) predicted the number of episodes of AUR and surgeries (open prostatectomy and transurethral resection of the prostate) related to BPH according to stages of evolution of the disease. Brazilian currency was converted to American dollars according to the theory of Purchasing Power Parity (PPP 2010: US$ 1 = R$ 1.70). RESULTS: The use of finasteride reduced 59.6% of AUR episodes and 57.9% the need of surgery compared to placebo, in a period of six years and taking into account a treatment discontinuity rate of 34%. The mean cost of treatment was R$ 764.11 (US$449.78) and R$ 579.57 (US$ 340.92) per patient in the finasteride and placebo groups, respectively. The incremental cost-effectiveness ratio (ICERs) was R$ 4.130 (US$ 2.429) per episode of AUR avoided and R$ 2.735 (US$ 1.609) per episode of surgery avoided. The comparison of finasteride + doxazosine to placebo showed a reduction of 75.7% of AUR episodes and 66.8% of surgeries in a 4 year time horizon, with a ICERs of R$ 21.191 (US$ 12.918) per AUR episodes avoided and R$ 11.980 (US$ 7.047) per surgery avoided. In the sensitivity analysis the adhesion rate to treatment and the cost of finasteride were the main variables that influenced the results. CONCLUSIONS: These findings suggest that the treatment of BPH with finasteride is cost-effective compared to placebo in the Brazilian public health system perspective.

Avaliação de sistema eletrônico para documentação clínica de enfermagem / Assessment of an electronic system for clinical nursing documentation

OBJETIVO: Apresentar a avaliação de um sistema eletrônico para documentação do processo de enfermagem (PE) na perspectiva de enfermeiras usuárias. MÉTODOS: Estudo exploratório, descritivo realizado com 16 enfermeiras do Hospital Universitário da Universidade de São Paulo. As enfermeiras avaliaram módulos e telas do sistema Sistema de Documentação Eletrônica do Processo de Enfermagem da Universidade de São Paulo- PROCEnf-USP, julgando o conforto visual, manuseio, clareza e abrangência da documentação, objetividade das informações e adequação do conteúdo ao registro de enfermagem em unidades clínico-cirúrgicas. RESULTADOS: A maioria das enfermeiras avaliou as características funcionais do PROCEnf-USP, como excelentes e muito boas, destacando o suporte ao raciocínio clínico ao apoiar decisões sobre diagnósticos, resultados e intervenções de enfermagem. Todas se posicionaram favoravelmente à implementação do PROCEnf-USP. CONCLUSÃO: Os resultados das avaliações mostraram que as enfermeiras estão estimuladas a adquirir novas habilidades técnicas e tecnológicas, com a adoção do PROCEnf-USP para a documentação do PE na realidade Institucional.

OBJECTIVE: To present the evaluation of an electronic system for documenting the nursing process (NP) from the perspective of nurse users. METHODS: This exploratory, descriptive study was conducted with 16 nurses at the University Hospital at the University of São Paulo. The nurses assessed modules and system screens of the Electronic Documentation System of the Nursing Process of the University of São Paulo (PROCEnf -USP) judging visual comfort, handling, clarity and completeness of documentation, objectivity and adequacy of the information content of the nursing record in clinical and surgical units. RESULTS: The majority of the nurses evaluated the functional characteristics of the PROCEnf-USP as excellent or very good, highlighting the clinical reasoning support for decisions about diagnoses, outcomes and nursing interventions. All positioned themselves favorably to the implementation of PROCEnf-USP. CONCLUSION: The results of the evaluations showed that the nurses are encouraged to acquire new technical skills and technology, with the adoption of PROCEnf-USP, for the documentation of the NP in the institutional reality.

OBJETIVO: Presentar la evaluación de un sistema electrónico para la documentación del proceso de enfermería (PE) en la perspectiva de enfermeras usuarias. MÉTODOS: Estudio exploratorio, descriptivo realizado con 16 enfermeras del Hospital Universitario de la Universidad de Sao Paulo. Las enfermeras evaluaron módulos y pantallas del Sistema de Documentación Electrónica del Proceso de Enfermería de la Universidad de Sao Paulo - PROCEnf-USP, juzgando el confort visual, manipulación, claridad y extensión de la documentación, objetividad de las informaciones y adecuación del contenido al registro de enfermería en unidades clínico-quirúrgicas. RESULTADOS: La mayoría de las enfermeras evaluó las características funcionales del PROCEnf-USP, como excelentes y muy buenas, destacando el soporte al raciocinio clínico al apoyar decisiones sobre diagnósticos, resultados e intervenciones de enfermería. Todas tomaron posición favorable respecto a la implementación del PROCEnf-USP. CONCLUSIÓN: Los resultados de la evaluaciones mostraron que las enfermeras están estimuladas para adquirir nuevas habilidades técnicas y tecnológicas, como la adopción del PROCEnf-USP para la documentación del PE en la realidad Institucional.

Desenvolvimento de Sistema Eletrônico de Documentação Clínica de Enfermagem estruturado em diagnósticos, resultados e intervenções / Desarrollo del Sistema Eletrónico de la Documentación Clínica de Enfermeria estructurado en diagnósticos, resultados e intervenciones / Development Eletronic Systems of Nursing Clinical Documentation structured by diagnosis, outcomes and interventions

A documentação eletrônica de enfermagem constitui documentos técnicos, científicos, legais e éticos de saúde. Este artigo é o relato de estudo de desenvolvimento de um sistema de documentação eletrônica de enfermagem. O sistema foi desenvolvido em 4 fases (conceituação, detalhamento, elaboração de protótipo e implantação) e a base de conhecimento foi organizada em hierarquia de domínios e classes, segundo a estrutura unificada das classificações NANDA-I, NIC e NOC. O resultado foi o desenvolvimento do sistema eletrônico PROCEnf-USP (Sistema de Documentação Eletrônica do Processo de Enfermagem da Universidade de São Paulo) que permite a documentação clínica e a geração de relatórios do processo de enfermagem, além de fornecer apoio às decisões sobre diagnósticos, resultados esperados e intervenções de enfermagem. Os fatores de êxito desse projeto de produção tecnológica compreenderam a articulação de diferentes áreas de conhecimento, bem como a valorização do contínuo aprimoramento teórico-prático do processo de enfermagem da instituição.

Electronic nursing documentation constitutes technical, scientific, legal and ethical documents. This paper reports a study to develop an electronic nursing documentation system. The system was developed in four phases (conceptualizing, detailing, prototype building and implementation), and the knowledge base was based on domains and classes according to the NANDA-I, NIC, and NOC unified framework. The result was an electronic system (PROCEnf-USP - Nursing Process Electronic Documentation System of the University of São Paulo) for electronic nursing process documentation and reports, including a functionality to support decisions on nursing diagnosis, expected outcomes, and interventions. The factors of success of this technological project included integrating varied fields of knowledge, as also as the institutional feature of valuing the continuous theoretical and practical improvement of the nursing process.

La documentación electrónica de enfermería produce documentos técnicos, científicos, jurídicos y éticos de salud. El objetivo diste articulo es relatar lo desarrollo de un sistema de documentación electrónica para la enfermería. El sistema fue desarrollado en 4 etapas (conceptualización, detalles, creación de prototipo y implantación) y la base de conocimientos fue organizada en jerarquía de dominios y clases, según la estructura unificada de las clasificaciones de la NANDA-I, NIC y la NOC. El sistema PROCEnf-USP (Sistema de Documentación Electrónica del Processo de Enfermería de la Universidad de São Paulo) desarrollado permite la documentación clínica y la producción de reportos del proceso de enfermería, bien como apoya las decisiones sobre los diagnósticos, resultados esperados y intervenciones de enfermería. Los factores de éxito del proyecto de producción tecnológica comprenderán la integración de diferentes campos del conocimiento y la valoración del continuo desarrollo teórico-práctico del proceso de enfermería de la institución.