The role of the vascular endothelium in arenavirus haemorrhagic fevers.

Viral haemorrhagic fevers (VHF) caused by arenaviruses are among the most devastating emerging human diseases. The most important pathogen among the arenaviruses is Lassa virus (LASV), the causative agent of Lassa fever that is endemic to West Africa. On the South American continent, the New World arenavirus Junin virus (JUNV), Machupo (MACV), Guanarito (GTOV), and Sabia virus (SABV) have emerged as causative agents of severe VHFs. Clinical and experimental studies on arenavirus VHF have revealed a crucial role of the endothelium in their pathogenesis. However, in contrast to other VHFs, haemorrhages are not a salient feature of Lassa fever and fatal cases do not show overt destruction of vascular tissue. The functional alteration of the vascular endothelium that precede shock and death in fatal Lassa fever may be due to more subtle direct or indirect effects of the virus on endothelial cells. Haemorrhagic disease manifestations and vascular involvement are more pronounced in the VHF caused by the South American haemorrhagic fever viruses. Recent studies on JUNV revealed perturbation of specific endothelial cell function, including expression of cell adhesion molecules, coagulation factors, and vasoactive mediators as a consequence of productive viral infection. These studies provided first possible links to some of the vascular abnormalities observed in patients, however, their relevance in vivo remains to be investigated.

Structural alterations of the coronary arterial wall are associated with myocardial flow heterogeneity in type 2 diabetes mellitus.

PURPOSE: To determine the relationship between carotid intima-media thickness (IMT), coronary artery calcification (CAC), and myocardial blood flow (MBF) at rest and during vasomotor stress in type 2 diabetes mellitus (DM). METHODS: In 68 individuals, carotid IMT was measured using high-resolution vascular ultrasound, while the presence of CAC was determined with electron beam tomography (EBT). Global and regional MBF was determined in milliliters per gram per minute with (13)N-ammonia and positron emission tomography (PET) at rest, during cold pressor testing (CPT), and during adenosine (ADO) stimulation. RESULTS: There was neither a relationship between carotid IMT and CAC (r = 0.10, p = 0.32) nor between carotid IMT and coronary circulatory function in response to CPT and during ADO (r = -0.18, p = 0.25 and r = 0.10, p = 0.54, respectively). In 33 individuals, EBT detected CAC with a mean Agatston-derived calcium score of 44 +/- 18. There was a significant difference in regional MBFs between territories with and without CAC at rest and during ADO-stimulated hyperemia (0.69 +/- 0.24 vs. 0.74 +/- 0.23 and 1.82 +/- 0.50 vs. 1.95 +/- 0.51 ml/g/min; p < or = 0.05, respectively) and also during CPT in DM but less pronounced (0.81 +/- 0.24 vs. 0.83 +/- 0.23 ml/g/min; p = ns). The increase in CAC was paralleled with a progressive regional decrease in resting as well as in CPT- and ADO-related MBFs (r = -0.36, p < or = 0.014; r = -0.46, p < or = 0.007; and r = -0.33, p < or = 0.041, respectively). CONCLUSIONS: The absence of any correlation between carotid IMT and coronary circulatory function in type 2 DM suggests different features and stages of early atherosclerosis in the peripheral and coronary circulation. PET-measured MBF heterogeneity at rest and during vasomotor stress may reflect downstream fluid dynamic effects of coronary artery disease (CAD)-related early structural alterations of the arterial wall.

Cuidar de pessoa incapacitada por acidente vascular cerebral no domicílio: o fazer do cuidador familiar

Estudo exploratório, descritivo e quantitativo que busca identificar e descrever as atividades do familiar que cuida de pessoas incapacitadas por AVC no domicílio. A amostra constituiu-se de 35 cuidadores familiares, predominantemente mulheres, esposas ou filhas. Os cuidados realizados relacionam-se ao grau de incapacidade do familiar. As orientações recebidas denotam falta de compromisso dos profissionais com a continuidade do cuidado. O cuidador aprende a cuidar no cotidiano, com base na observação e auxílio à enfermagem na internação. As dificuldades pautam-se no esforço físico, na desinformação e no medo, no constrangimento e na vergonha em lidar com o corpo do outro. O estudo enfoca a necessidade do preparo para a alta hospitalar, salienta a família como espaço concreto para o cuidado; o aumento da expectativa de vida é uma constatação.

Intraoperative assessment of vascular access.

PURPOSE: The intraoperative quality assessment of the arteriovenous fistula for hemodialysis is an essential process to limit early failure due to technical problems or inadequate vascular quality. This step is not clearly defined in the literature with no recommendations. METHODS: We selected published articles related to the topic of intraoperative quality control of the vascular access for hemodialysis. RESULTS: The intraoperative blood flow measurement greater than 120 ml/min in autologous fistula and less than 320 ml/min in arteriovenous graft was described as predictive factors for early failure. CONCLUSIONS: The blood flow measurement should be performed after the confection of the anastomosis. When blood flow is limited, fistulography is an essential step to assess patency.

Vascular dysfunction in children conceived by assisted reproductive technologies: underlying mechanisms and future implications.

Epidemiological studies in humans have demonstrated a relationship between pathological events during fetal development and increased cardiovascular risk later in life and have led to the so called "Fetal programming of cardiovascular disease hypothesis". The recent observation of generalised vascular dysfunction in young apparently healthy children conceived by assisted reproductive technologies (ART) provides a novel and potentially very important example of this hypothesis. This review summarises recent data in ART children demonstrating premature subclinical atherosclerosis in the systemic circulation and pulmonary vascular dysfunction predisposing to exaggerated hypoxia-induced pulmonary hypertension. These problems appear to be related to the ART procedure per se. Studies in ART mice demonstrating premature vascular aging and arterial hypertension further demonstrate the potential of ART to increase cardiovascular risk and have allowed to unravel epigenetic alterations of the eNOS gene as an underpinning mechanism. The roughly 25% shortening of the life span in ART mice challenged with a western style high-fat-diet demonstrates the potential importance of these alterations for the long-term outcome. Given the young age of the ART population, data on cardiovascular endpoints will not be available before 20 to 30 years from now. However, already now cohort studies of the ART population are needed to early detect cardiovascular alterations with the aim to prevent or at least optimally treat cardiovascular complications. Finally, a debate needs to be engaged on the future of ART and the consequences of its exponential growth for public health.

Adenovirus-mediated gene transfer into selected liver segments using a vascular exclusion technique.

Adenovirus-mediated gene therapy is hampered by severe virus-related toxicity, especially to the liver. The aim of the present study was to test the ability of a vascular exclusion technique to achieve transgene expression within selected liver segments, thus minimizing both viral and transgene product toxicity to the liver. An E1-E3-deleted replication-deficient adenovirus expressing a green fluorescent protein (GFP) reporter gene was injected into the portal vein of BDIX rats, with simultaneous clamping of the portal vein tributaries to liver segments II, III, IV, V, and VIII. GFP expression and inflammatory infiltrate were measured in the different segments of the liver and compared with those of the livers of animals receiving the viral vector in the portal vein without clamping. The GFP expression was significantly higher in the selectively perfused segments of the liver as compared with the non-perfused segments (p < 0.0001) and with the livers of animals that received the vector in the portal vein without clamping (p < 0.0001). Accordingly, the inflammatory infiltrate was more intense in the selectively perfused liver segments as compared with all other groups (p < 0.0001). Fluorescence was absent in lungs and kidneys and minimal in spleen. The clinical usefulness of adenovirus-mediated gene transfer to the liver largely depends on the reduction of its liver toxicity. Clamping of selected portal vein branches during injection allows for delivery of genes of interest to targeted liver segments. Transgene expression confined to selected liver segments may be useful in the treatment of focal liver diseases, including metastases.

A problemática do cuidador familiar do portador de acidente vascular cerebral

Objetivou-se identificar a problemática da família de pessoas acometidas de acidente vascular cerebral hospitalizadas e discutir as dificuldades do cuidador familiar para o cuidado no âmbito domiciliar. A amostra constou de 154 famílias de pacientes internados em um hospital da rede pública de saúde, Fortaleza-CE. Conforme os resultados denotam, a maioria dos cuidadores são mulheres, 104 (67,5%); 122 casos (79,2%) apresentam comprometimento familiar e alterações na vida diária em 115 dos acompanhantes (74,7%); 150 (97,4%) não receberam orientações acerca dos cuidados, mas 143 (92,9%) sentem-se seguros para acompanhá-los. O sentimento predominante foi a tristeza, 125 (81,2%), e as dúvidas principais foram: alimentação, 64 (41,6%), administração de medicamentos, 49 (29,9%), e possíveis complicações clínicas após a alta, 49 (29,9%). Estes resultados alertam para o papel do enfermeiro como educador, não somente na prevenção das doenças crônico-degenerativas, mas, também, na orientação aos cuidadores familiares sobre os cuidados dispensados após a alta hospitalar.

Embryonic vascular endothelial cells are malleable to reprogramming via Prox1 to a lymphatic gene signature.

BACKGROUND: In vivo studies demonstrate that the Prox1 transcription factor plays a critical role in the development of the early lymphatic system. Upon Prox1 expression, early lymphatic endothelial cells differentiate from the cardinal vein and begin to express lymphatic markers such as VEGFR-3, LYVE-1 and Podoplanin. Subsequent in vitro studies have found that differentiated vascular endothelial cells can be reprogrammed by Prox1 to express a lymphatic gene profile, suggesting that Prox1 can initiate the expression of a unique gene signature during lymphangiogenesis. While the in vitro data suggest that gene reprogramming occurs upon Prox1 expression, it is not clear if this is a direct result of Prox1 in vascular endothelial cells in vivo. RESULTS: Overexpression of Prox1 in vascular endothelial cells during embryonic development results in the reprogramming of genes to that of a more lymphatic signature. Consequent to this overexpression, embryos suffer from gross edema that results in embryonic lethality at E13.5. Furthermore, hemorrhaging and anemia is apparent along with clear defects in lymph sac development. Alterations in junctional proteins resulting in an increase in vascular permeability upon Prox1 overexpression may contribute to the complications found during embryonic development. CONCLUSION: We present a novel mouse model that addresses the importance of Prox1 in early embryonic lymphangiogenesis. It is clear that there needs to be a measured pattern of expression of Prox1 during embryonic development. Furthermore, Prox1 reprograms vascular endothelial cells in vivo by creating a molecular signature to that of a lymphatic endothelial cell.

Vitamin E but not 17B-estradiol protect against vascular toxicity induced by B-amyloid wild type and the Dutch amyploid variant

Amyloid β-peptide (Aβ) fibril deposition on cerebral vessels produces cerebral amyloid angiopathy that appears in the majority of Alzheimer's disease patients. An early onset of a cerebral amyloid angiopathy variant called hereditary cerebral hemorrhage with amyloidosis of the Dutch type is caused by a point mutation in Aβ yielding AβGlu22→Gln. The present study addresses the effect of amyloid fibrils from both wild-type and mutated Aβ on vascular cells, as well as the putative protective role of antioxidants on amyloid angiopathy. For this purpose, we studied the cytotoxicity induced by Aβ1–40 Glu22→Gln and Aβ1–40 wild-type fibrils on human venule endothelial cells and rat aorta smooth muscle cells. We observed that AβGlu22→Gln fibrils are more toxic for vascular cells than the wild-type fibrils. We also evaluated the cytotoxicity of Aβ fibrils bound with acetylcholinesterase (AChE), a common component of amyloid deposits. Aβ1–40 wild-type–AChE fibrillar complexes, similar to neuronal cells, resulted in an increased toxicity on vascular cells. Previous reports showing that antioxidants are able to reduce the toxicity of Aβ fibrils on neuronal cells prompted us to test the effect of vitamin E, vitamin C, and 17β-estradiol on vascular damage induced by Aβwild-type and AβGlu22→Gln. Our data indicate that vitamin E attenuated significantly the Aβ-mediated cytotoxicity on vascular cells, although 17β-estradiol and vitamin C failed to inhibit the cytotoxicity induced by Aβ fibrils.

Demographic and geographic vascular risk factor differences in European young adults with ischemic stroke: the 15 cities young stroke study.

BACKGROUND AND PURPOSE: We compared among young patients with ischemic stroke the distribution of vascular risk factors among sex, age groups, and 3 distinct geographic regions in Europe. METHODS: We included patients with first-ever ischemic stroke aged 15 to 49 years from existing hospital- or population-based prospective or consecutive young stroke registries involving 15 cities in 12 countries. Geographic regions were defined as northern (Finland, Norway), central (Austria, Belgium, France, Germany, Hungary, The Netherlands, Switzerland), and southern (Greece, Italy, Turkey) Europe. Hierarchical regression models were used for comparisons. RESULTS: In the study cohort (n=3944), the 3 most frequent risk factors were current smoking (48.7%), dyslipidemia (45.8%), and hypertension (35.9%). Compared with central (n=1868; median age, 43 years) and northern (n=1330; median age, 44 years) European patients, southern Europeans (n=746; median age, 41 years) were younger. No sex difference emerged between the regions, male:female ratio being 0.7 in those aged <34 years and reaching 1.7 in those aged 45 to 49 years. After accounting for confounders, no risk-factor differences emerged at the region level. Compared with females, males were older and they more frequently had dyslipidemia or coronary heart disease, or were smokers, irrespective of region. In both sexes, prevalence of family history of stroke, dyslipidemia, smoking, hypertension, diabetes mellitus, coronary heart disease, peripheral arterial disease, and atrial fibrillation positively correlated with age across all regions. CONCLUSIONS: Primary preventive strategies for ischemic stroke in young adults-having high rate of modifiable risk factors-should be targeted according to sex and age at continental level.

Diagnóstico de enfermagem: mobilidade física prejudicada em pacientes acometidos por acidente vascular encefálico

O estudo teve como objetivo investigar a ocorrência do diagnóstico de enfermagem Mobilidade Física Prejudicada em pacientes com AVE. Estudo exploratório, desenvolvido em unidades de reabilitação, de novembro de 2007 a março de 2008, por meio de entrevista e exame físico. A Taxonomia II da NANDA foi utilizada para a identificação do diagnóstico. Foram avaliados 121 indivíduos, com idade média de 62,1 anos, 52,3% homens, com média de 1,5 episódio de AVE em 3,4 anos. O diagnóstico esteve presente em 90%, com média de 5,8 características definidoras. Dificuldade para virar-se foi a característica mais presente, e 3,4 fatores foram relacionados por paciente, com destaque para a Força muscular diminuída, além de Prejuízos neuromusculares (100%). Destaca-se a necessidade de enfocar-se esse diagnóstico no planejamento das intervenções após o AVE, com vistas à promoção da saúde desses pacientes.

Indicadores para avaliação do acesso vascular de usuários em hemodiálise

Os objetivos deste estudo foram construir indicadores para avaliar a qualidade das práticas assistenciais relacionadas ao acesso vascular de usuários em hemodiálise (HD) e proceder à validação dos indicadores. As etapas para elaborar os indicadores constituíram-se de seleção das práticas assistenciais relacionadas ao acesso vascular, fundamentação teórica dessas práticas e construção de quatro indicadores, segundo o modelo Donabediano: desempenho de cateter temporário duplo lúmen para HD, manutenção de cateter temporário de duplo lúmen, monitoramento de fístula arteriovenosa e complicações de fístula arteriovenosa. A coleta de dados ocorreu entre outubro e novembro de 2008, por meio de um questionário composto pelo julgamento do manual operacional, dos atributos dos indicadores e de seus componentes. A validação foi realizada por nove juízes, e todos os indicadores foram validados sob o consenso mínimo de 75%. Acredita-se que o emprego dessa ferramenta contribua para a avaliação e gestão da qualidade nos serviços de hemodiálise.