Arterial variants are an important consideration in the care of individuals undergoing surgery or invasive diagnostic procedures. Although there are numerous reports that describe arterial variants in localized body regions, it is unknown if some individuals have a proclivity for the development of arterial variants. The current study set out to determine if some individuals do, in fact, have a proclivity for vascular variants and further, if one arterial variant can predict the presence of another variant. To accomplish this, whole-body dissection was performed on 18 anatomical body donors. In each donor, the entire arterial tree was followed and documented. The findings from this study suggest that arterial variants are extremely common and the presence of numerous variants is frequent.

A obesidade pode mudar as características das células endoteliais e musculares lisas (CMLVs). Reatividade e genes inflamatórios e de marcadores de fenótipo de CMLVs foram avaliados em artérias mesentéricas de resistência (AMRs) e de aorta de camundongos alimentados com dieta hiperlipídica (OB). RNAm para citocinas pró-inflamatórias e IL-10 foi aumentado em AMRs e aorta de OB. O relaxamento não foi alterado, mas a contração foi reduzida em AMRs e aorta de OB. AMRs apresentaram redução global da contração e a aorta apresentou redução específica para agonista adrenérgico. Maior modulação negativa por NO e prostanoides vasodilatadores foi observada em aorta, mas não em AMRs. RNAm para marcador do fenótipo sintético foi aumentado em AMRs de OB. Esses resultados mostram que as células endoteliais e as CMLVs de AMRs e aorta respondem diferentemente à obesidade. Inflamação e mecanismo de contrarregulação são induzidos em AMRs e aorta, que impediria a disfunção endotelial, mas não a mudança fenotípica das CMLVs em AMRs, que então, comprometeria sua capacidade contrátil. / Obesity may change the vascular endothelial cells and smooth muscle cells (VSMC) characteristics. Vascular reactivity and inflammatory and phenotypic markers for VSMC gene expression in resistance mesenteric arteries (RMA) and aorta from mice fed with high fat diet (OB). Pro-inflammatory cytokines mRNA and IL-10 were elevated in OB\'s RMA and aorta. The relaxation wasnt altered, however a reduction in contractility was observed in OB\'s RMA and aorta. A global reduction in contractility was observed in RMA and aorta demonstrated a specific reduction to adrenergic agonist. Higher negative modulation by NO and vasodilator prostanoids were seen only in aorta. Phenotypic markers mRNA were elevated in OB\'s RMA. The results shows that endothelial cells and VSMC from RMA and aorta respond differently to obesity. Inflammation and counter regulatory mechanisms are induced in RMA and aorta of which would prevent endothelial dysfunction but not VSMC phenotypic changing from RMA, compromising the contractile ability.

Physiologically relevant scaffold-based tissue engineered structures have been limited in scope and viability by the diffusion limits of oxygen and other nutrients and functions provided by native vasculature in vivo. This has prevented the maintenance of healthy cell populations in scaffolds that are more than 200痠 thick. Combining concepts from microfluidics with biomaterials engineering, this project set out to engineer a perfusable fibrin-based vascular network capable of physiologically relevant flow properties as well as diffusion that supports viable cell populations. To create this system, a small artery sized (1.5 mm wide) gelatin sacrificial structure was embedded inside of a block of robust fibrin gel (4.26% w/v fibrin) then melted and rinsed out to create a perfusable vascular network. Characterization consisted of morphometric and histological analyses for channel sizes compared to the sacrificial structures, particle tracking to observe flow properties, and fluorescent dextran diffusion to measure diffusivity into the fibrin scaffold. We found that channels derived from sacrificial structures maintain their size and shape inside of the gel. Flow properties of the fluid through the channels were found to be both laminar and within expected physiological rates compared to native vessels of similar sizes. Cells on the surface of the fibrin vascular device expressed fluorescent markers that were delivered through the vascular network and perfused through the fibrin scaffold. These findings suggest that a fibrin based vascular system may provide a platform creating a functional vascular layer and for developing tissue engineered systems of increased size and complexity.

A hipertensão arterial sistêmica (HAS) apresenta alterações vasculares significativas como o remodelamento vascular e o aumento da atividade das metaloproteinases de matriz (MMPs), principalmente a MMP-2, responsáveis pela proteólise da matriz extracelular. No remodelamento vascular, ocorre uma mudança no fenótipo das células musculares lisas vasculares (CMLV) de contrátil para sintético, com redução de proteínas da maquinaria contrátil como a calponina-1. Essa alteração fenotípica confere às CMLV a capacidade de migração e proliferação, contribuindo ao remodelamento arterial durante a HAS. A calponina-1 foi degradada pela MMP-2 em aorta de ratos endotoxêmicos e este efeito contribuiu para a menor contração vascular da sepse. Sua redução foi associada ao aumento de atividade de MMP-2 e proliferação de CMLV em aortas de ratos hipertensos. A hipótese do presente trabalho é de que a MMP-2 contribui para as alterações morfofuncionais induzidas pela hipertensão em artérias de condutância e de resistência pela regulação de calponina-1. Para testar tal hipótese, ratos Wistar foram submetidos ao modelo de hipertensão dois rins-um clipe (2R-1C) ou apenas laparatomia e tratados por via oral com doxiciclina (inibidor da atividade de MMPs na dose de 30 mg/kg/dia) ou água durante sete dias. A pressão arterial sistólica (PAS) foi aferida diariamente por pletismografia de cauda. Aorta e artérias mesentéricas foram removidas para a execução de zimografia in situ e em gel, imunofluorescência para calponina-1, imunohistoquímica para Ki-67 e análise morfológica. Artérias mesentéricas e aortas também foram utilizadas para curva concentração-efeito com fenilefrina. Observou-se que a PAS aumentou em ratos 2R-1C e o tratamento com doxiciclina não a reduziu. A análise morfológica da aorta mostrou que a razão média por lúmen e a área de secção transversal aumentaram nos animais hipertensos em relação aos grupos Sham. Não houve alteração nestes parâmetros nas artérias mesentéricas. Houve aumento de proliferação das CMLV em aortas de ratos 2R-1C e a doxiciclina reverteu essa alteração. Nas artérias mesentéricas não foi observada alteração na proliferação celular. A atividade gelatinolítica de MMP-2 e sua expressão estão aumentadas nos dois leitos arteriais de ratos 2R-1C e o tratamento com doxiciclina as reduziu. A expressão de calponina-1 está reduzida nas aortas e aumentada nas artérias de resistência de animais 2R-1C e o tratamento reverteu estes efeitos. A contração à fenilefrina das aortas e artérias mesentéricas está aumentada nos animais 2R-1C e o tratamento a reduziu. Os resultados indicam que a MMP-2 tem ações diferentes na regulação de calponina-1 nos dois leitos arteriais. Nas artérias de condutância, a redução de calponina-1 pela MMP-2 pode ser o gatilho para a mudança de fenótipo das células musculares lisas vasculares, o que conduz ao remodelamento hipertrófico. Nas artérias de resistência, a MMP-2 pode contribuir para a função contrátil do leito arterial aumentando os níveis de calponina-1. / Hypertension is a global public health problem that lead to significant vascular changes. Among them, the chronic remodeling and increased activity of matrix metalloproteinase (MMP)-2, which is responsible for extracellular matrix proteolysis, are the main mediators of the vascular maladaptation. During vascular remodeling, there is a change in the phenotype of vascular smooth muscle cells (VSMC) of contractile to synthetic form, with a reduction of contractile proteins such as calponin-1. This phenotype switch provides to the VSMC the ability of migration and proliferation, thus contributing to hypertension-induced arterial remodeling. Calponin-1 was degraded by MMP-2 in rat endotoxemic aortas and this effect contributed to the vascular hypocontractility. In addition, its reduction was associated with increased activity of MMP-2 and proliferation of VSMC in aortas of rats submitted to renovascular hypertension. Therefore, the hypothesis of this study is that MMP-2 contributes to hypertension-induced morphological and functional changes in conductance and resistance arteries by regulating calponin-1. To test such hypothesis, male Wistar rats were submitted to the two kidney- one clipe (2K-1C) hypertension model and were treated with doxycycline (inhibitor of MMPs activity at 30 mg/kg/day) or water for one week. Systolic blood pressure (SBP) was daily checked by tail-cuff plethysmography. Aortas and mesenteric arteries were removed to perform in situ and gel zymography, immunofluorescence for calponin-1, immunohistochemistry for Ki-67 and morphological analysis. Mesenteric arteries and aortas were also used for concentration-effect curve for phenylephrine. It was observed that SBP has increased in 2K-1C rats and doxycycline did not reduce it. Morphological analysis of the aorta showed that both media per lumen ratio and arterial cross sectional area increased in hypertensive animals compared to Sham. There was no changes in this two parameters in mesenteric arteries. Furthermore, there was an increase of VSMC proliferation in rat aortas and doxycycline was able to revert this alteration. In the mesenteric arteries, no changes were observed in VSMC proliferation. Gelatinolytic activity of MMP-2 and its expression were increased in both arterial beds of 2K-1C rats and treatment with doxycycline reduced it. Calponin-1 expression was reduced in aortas and increased in resistance arteries from 2K-1C animals and the treatment was able to improve both scenarios. The contractile function of aortas and mesenteric arteries was increased in 2K-1C rats and treatment has reduced it. So, what follows is that MMP-2 has different actions in the regulation of calponin-1 in both arterial beds. In conductance arteries, reduction of calponin-1 by MMP-2 may trigger the VSMC phenotype switch, which leads to the hypertrophic remodeling. In resistance arteries, MMP-2 contributes to the hypercontractility of the arterial bed by increasing calponin-1. This effect may be particularly related to extracellular actions of MMP-2.

Made available in DSpace on 2019-03-30T00:18:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-12-19 / INTRODUCTION: Stroke is a third cause of death and disability in developed countries, being one of the major health problems worldwide. Intravenous thrombolysis with alteplase, alone or later endovascular thrombectomy, is an effective treatment for acute ischemic stroke, and should be administered within up to 4.5 hours and takes into account a number of factors, including the ¿weekend effect¿. OBJECTIVE: To evaluate the parameters of initial care for patients undergoing intravenous thrombolytic therapy treated at a tertiary center. METHODS: Retrospective cohort study, conducted at the General Hospital of Fortaleza (HGF), Ceará, Brazil. We analyzed all records of Emergency Nursing and the medical records of patients who underwent thrombolytic therapy from May 2015 to April 2016. Initially, all available data were cataloged on the form and, based on this initial strategy A review of all medical records of those who possibly underwent thrombolysis was performed. RESULTS: A total of 1361 files of patients with suspected stroke were analyzed, and it was designed to analyze 201 patients who underwent thrombolysis. The mean age was 66 years, the majority of males (58%), as major comorbidities such as hypertension (73%) and diabetes (29%), regarding the classification of BAMFORD, more common for a syndrome of total circulation above (48%). The time of onset of the clinical picture in turn with an average of 143 minutes, the time of installation to the computed tomography in the media of 15 minutes and the time of the needle had an average of 51 minutes. (P <0.04) and the time of the needle-holder was shorter without daytime (49 ± 18 minutes, p <0.04). The time of onset of the clinical condition was new at night time (133 ± 52 minutes, p <0.04). CONCLUSION: The times related to thrombolysis are within the international prayers, with influence of the period of the day on them. The "weekend effect" was not found. Key words: stroke; thrombolytic therapy; weekend effect. / INTRODUÇÃO: O acidente vascular cerebral é a terceira causa de morte e incapacidade nos países desenvolvidos, sendo um dos principais problemas de saúde em todo o mundo. A trombólise intravenosa com alteplase, sozinha ou seguida de trombectomia endovascular, é um tratamento eficaz para o acidente vascular encefálico isquêmico agudo, devendo ser administrada dentro de até 4,5 horas e leva em conta uma série de fatores, dentre eles o ¿efeito de final de semana¿. OBJETIVO: Avaliar os parâmetros do atendimento inicial a pacientes submetidos à terapia trombolítica endovenosa atendidos em um centro terciário. METODOLOGIA: Estudo do tipo coorte retrospectiva, realizado no Hospital Geral de Fortaleza (HGF), Ceará, Brasil. Foram analisadas todas as fichas de acolhimento da Enfermagem da Emergência e os prontuários dos pacientes que realizaram a terapia trombolítica no período de maio de 2015 a abril de 2016. Inicialmente, foram catalogados todos os dados presentes na ficha e, a partir dessa triagem inicial, foi realizado uma revisão de todos os prontuários daqueles que possivelmente realizaram a trombólise. RESULTADOS: Foram analisadas 1361 fichas de pacientes com suspeita de acidente vascular cerebral, sendo considerados para análise os 201 pacientes que realizaram trombólise. A média de idade foi de 66 anos, a maioria do sexo masculino (58%), as principais comorbidades foram hipertensão arterial (73%) e diabetes (29%), quanto à classificação do BAMFORD, a mais comum foi a Síndrome da circulação anterior total (48%). O tempo do início do quadro clinico à chegada teve média de 143 minutos, o tempo de chegada à tomografia computadorizada foi, em média, de 15 minutos e o tempo porta-agulha apresentou média de 51 minutos. O tempo do início do quadro clinico à chegada foi menor no período noturno (133±52 minutos, p<0,04) e o tempo porta-agulha foi menor no período diurno (49±18 minutos, p<0,04). CONCLUSÃO: Os tempos relacionados à trombólise estão dentro das recomendações internacionais, havendo influência do período do dia sobre os mesmos. Não foi encontrado o ¿efeito de final de semana¿. Palavras-chaves: acidente vascular cerebral; terapia trombolítica; efeito de final de semana.

A hipertensão arterial sistêmica (HAS) apresenta alterações vasculares significativas como o remodelamento vascular e o aumento da atividade das metaloproteinases de matriz (MMPs), principalmente a MMP-2, responsáveis pela proteólise da matriz extracelular. No remodelamento vascular, ocorre uma mudança no fenótipo das células musculares lisas vasculares (CMLV) de contrátil para sintético, com redução de proteínas da maquinaria contrátil como a calponina-1. Essa alteração fenotípica confere às CMLV a capacidade de migração e proliferação, contribuindo ao remodelamento arterial durante a HAS. A calponina-1 foi degradada pela MMP-2 em aorta de ratos endotoxêmicos e este efeito contribuiu para a menor contração vascular da sepse. Sua redução foi associada ao aumento de atividade de MMP-2 e proliferação de CMLV em aortas de ratos hipertensos. A hipótese do presente trabalho é de que a MMP-2 contribui para as alterações morfofuncionais induzidas pela hipertensão em artérias de condutância e de resistência pela regulação de calponina-1. Para testar tal hipótese, ratos Wistar foram submetidos ao modelo de hipertensão dois rins-um clipe (2R-1C) ou apenas laparatomia e tratados por via oral com doxiciclina (inibidor da atividade de MMPs na dose de 30 mg/kg/dia) ou água durante sete dias. A pressão arterial sistólica (PAS) foi aferida diariamente por pletismografia de cauda. Aorta e artérias mesentéricas foram removidas para a execução de zimografia in situ e em gel, imunofluorescência para calponina-1, imunohistoquímica para Ki-67 e análise morfológica. Artérias mesentéricas e aortas também foram utilizadas para curva concentração-efeito com fenilefrina. Observou-se que a PAS aumentou em ratos 2R-1C e o tratamento com doxiciclina não a reduziu. A análise morfológica da aorta mostrou que a razão média por lúmen e a área de secção transversal aumentaram nos animais hipertensos em relação aos grupos Sham. Não houve alteração nestes parâmetros nas artérias mesentéricas. Houve aumento de proliferação das CMLV em aortas de ratos 2R-1C e a doxiciclina reverteu essa alteração. Nas artérias mesentéricas não foi observada alteração na proliferação celular. A atividade gelatinolítica de MMP-2 e sua expressão estão aumentadas nos dois leitos arteriais de ratos 2R-1C e o tratamento com doxiciclina as reduziu. A expressão de calponina-1 está reduzida nas aortas e aumentada nas artérias de resistência de animais 2R-1C e o tratamento reverteu estes efeitos. A contração à fenilefrina das aortas e artérias mesentéricas está aumentada nos animais 2R-1C e o tratamento a reduziu. Os resultados indicam que a MMP-2 tem ações diferentes na regulação de calponina-1 nos dois leitos arteriais. Nas artérias de condutância, a redução de calponina-1 pela MMP-2 pode ser o gatilho para a mudança de fenótipo das células musculares lisas vasculares, o que conduz ao remodelamento hipertrófico. Nas artérias de resistência, a MMP-2 pode contribuir para a função contrátil do leito arterial aumentando os níveis de calponina-1. / Hypertension is a global public health problem that lead to significant vascular changes. Among them, the chronic remodeling and increased activity of matrix metalloproteinase (MMP)-2, which is responsible for extracellular matrix proteolysis, are the main mediators of the vascular maladaptation. During vascular remodeling, there is a change in the phenotype of vascular smooth muscle cells (VSMC) of contractile to synthetic form, with a reduction of contractile proteins such as calponin-1. This phenotype switch provides to the VSMC the ability of migration and proliferation, thus contributing to hypertension-induced arterial remodeling. Calponin-1 was degraded by MMP-2 in rat endotoxemic aortas and this effect contributed to the vascular hypocontractility. In addition, its reduction was associated with increased activity of MMP-2 and proliferation of VSMC in aortas of rats submitted to renovascular hypertension. Therefore, the hypothesis of this study is that MMP-2 contributes to hypertension-induced morphological and functional changes in conductance and resistance arteries by regulating calponin-1. To test such hypothesis, male Wistar rats were submitted to the two kidney- one clipe (2K-1C) hypertension model and were treated with doxycycline (inhibitor of MMPs activity at 30 mg/kg/day) or water for one week. Systolic blood pressure (SBP) was daily checked by tail-cuff plethysmography. Aortas and mesenteric arteries were removed to perform in situ and gel zymography, immunofluorescence for calponin-1, immunohistochemistry for Ki-67 and morphological analysis. Mesenteric arteries and aortas were also used for concentration-effect curve for phenylephrine. It was observed that SBP has increased in 2K-1C rats and doxycycline did not reduce it. Morphological analysis of the aorta showed that both media per lumen ratio and arterial cross sectional area increased in hypertensive animals compared to Sham. There was no changes in this two parameters in mesenteric arteries. Furthermore, there was an increase of VSMC proliferation in rat aortas and doxycycline was able to revert this alteration. In the mesenteric arteries, no changes were observed in VSMC proliferation. Gelatinolytic activity of MMP-2 and its expression were increased in both arterial beds of 2K-1C rats and treatment with doxycycline reduced it. Calponin-1 expression was reduced in aortas and increased in resistance arteries from 2K-1C animals and the treatment was able to improve both scenarios. The contractile function of aortas and mesenteric arteries was increased in 2K-1C rats and treatment has reduced it. So, what follows is that MMP-2 has different actions in the regulation of calponin-1 in both arterial beds. In conductance arteries, reduction of calponin-1 by MMP-2 may trigger the VSMC phenotype switch, which leads to the hypertrophic remodeling. In resistance arteries, MMP-2 contributes to the hypercontractility of the arterial bed by increasing calponin-1. This effect may be particularly related to extracellular actions of MMP-2.

Le sepsis, caractérisé par une réponse systémique inadaptée, demeure une des principales causes de mortalité. Les principaux mécanismes des défaillances d’organes induites par le sepsis sont d’étiologie vasculaire et/ou inflammatoire. Notre hypothèse est que la dysfonction vasculaire entraîne une baisse exagérée de la perfusion et de l’oxygénation des organes et ainsi une détérioration de leur fonction, l’ensemble pouvant mener au décès.Dans ce contexte physiopathologique complexe, l’objectif était d’étudier 2 pistes thérapeutiques nouvelles qui modulent, l’une la réponse inflammatoire des organes par l’érythropoïétine (EPO) et l’autre l’un des principaux effecteurs de la dysfonction vasculaire, l’adrénomédulline (ADM). Nos résultats montrent que, lors du sepsis :- l'EPO prévient la réponse inflammatoire et le stress oxydant dans les organes etdans le plasma et a un effet positif sur la mortalité précoce. Cependant, les doses pour obtenir ces effets cytoprotecteurs sont élevées.- l’Adrezicumab (ADZ), anticorps inhibant partiellement l’ADM, restaure une pression artérielle et un débit cardiaque corrects précocement. Si l’ADZ prévient les dysfonctionsvasculaire, métabolique et cardiaque au cours du sepsis et/ou diminue la nécessité de recours aux vasopresseurs, cela ouvrirait des perspectives thérapeutiques majeures.En conclusion, les pistes thérapeutiques testées sont d’intérêt. Pour établir le potentiel chez l’Homme, l’utilisation de dérivés non-hémapoïétiques de l’EPO serait engageante et demande d’autres investigations. L’approche immunologique, telle celle ciblant l’ADM est prometteuse, les effets à long terme sont encore à établir. , / Sepsis, characterized by inadequate systemic response with organ failure, remains amajor cause of death worldwide. The main mechanisms of sepsis-induced organ dysfunctionare from vascular and inflammatory etiologies. Our hypothesis was that vascular dysfunctioninduced a major drop in perfusion and oxygenation of organs and in turn a deterioration offunction, all of which lead to death.In this multifactorial pathophysiological background, our objective was to investigate2 novel therapeutic approaches able to modulate, one the inflammatory response of failingorgans through the use of erythropoietin (EPO) and the other one the key effector ofvascular dysfunction in sepsis, adrenomedullin (ADM).Our results show that during sepsis:- EPO prevents, inflammatory response and oxidative stress in organs and in theplasma and in turn death. The doses for these cytoprotective effects are high.- the Adrezicumab (ADZ) through the partial inhibition of the ADM and themodulation of vasodilation, rapidly improved, during sepsis, blood pressure and cardiacoutput and could thus prevent the onset of organ dysfunction related to sepsis. IfAdrecizumab prevents vascular, metabolic and cardiac dysfunction during sepsis and/orreduces the need for use of vasopressors, it would open major therapeutic perspectives.In conclusion, all together we provide new evidence that on one hand the use of nonhematopoieticderivatives of EPO could be promising but request further investigations andon the other, the immunologic approach such as targetting ADM could be of high interest inthe treatment of sepsis.

acase@tulane.edu / Multiple sclerosis (MS) is a common neurodegenerative disease and remains an unmet clinical challenge. In MS, an autoimmune response leads to immune cell infiltration, inflammation, demyelination, and lesions in central nervous system (CNS) tissues resulting in tremors, fatigue, and progressive loss of motor function. These pathologic hallmarks are effectively reproduced in the murine experimental autoimmune encephalomyelitis (EAE) model. Using the EAE mouse, we have defined critical time points during the disease progression that have correlative immunopathology with those that occur in MS. As promising therapeutic alternatives to treat MS, we investigated the fresh, heterogeneous population of cells from adipose called the stromal vascular fraction (SVF), which contains adipose-derived stromal/stem cells (ASCs). With these studies, we evaluated the therapeutic efficacies of fresh SVF cells and culture-expanded ASCs at early and late stage EAE disease after intraperitoneal (i.p.) administration. At early stage EAE disease, autoimmune reactions and inflammation are prevalent in the periphery lead to CNS damage by the infiltration of cells that generate inflammatory and demyelinating lesions. We demonstrated that at this time, treatment with SVF cells and ASCs were incapable of attenuating CNS pathology. However, the potency of SVF cells to suppress the autoimmune reactions in the periphery was strong enough to partially ameliorate motor impairments. Furthermore, we revealed the altered gene expressions of the SVF cells and ASCs when exposed to this pathogenic milieu in vitro. Not only did we show that the majority of the helper T (TH) cells contained within the SVF are of the TH2 phenotype, but the most enhanced cytokines in response to the inflammatory milieu were interleukin-10 (IL-10) and transforming growth factor-β (TGFβ) which promote regulatory T cells (Tregs). The most dominant increase detected in ASCs was interleukin-6 (IL-6) which correlates with the inability of ASCs to suppress the activities of the pathogenic T cells at early stage disease. At late stage disease, we showed the greatest improvements in SVF-treated EAE mice that led to amelioration to pathology in CNS tissues and partial restoration of motor function. The most pronounced changes following SVF treatment were the high levels of IL-10 in the peripheral blood, lymphoid and CNS tissues along with the induction of regulatory T cells in the lymph nodes which indicated potent immunomodulatory effects. These effects were not as robust following ASC treatment. A deeper investigation into the potential mechanisms showed phenotypes of T cells and macrophages skewed towards favorable phenotypes. SVF treatment shifted the TH cell subsets away from the effector TH1 and TH2 and toward the Tregs which promote immune tolerance and anti-inflammatory effects. Furthermore, the Treg-associated effects involve the induction of the alternative activation phenotype of macrophages, or M2, which were evidenced in the spleens and CNS tissues of SVF-treated EAE mice. Moreover, we determined that i.p. injected ASCs, and more so, SVF cells were still present in the spleens of EAE mice after 5 days. Together, we investigated a novel modality for treating an inflammatory, autoimmune disease. By comparison with ASC treatment, we demonstrated potential mechanisms of SVF treatment at early and late stage EAE disease that are translational to the inflammatory and demyelinating phases MS disease, respectively. We determined that the timing of administration is most critical, and once active immune activities subside, SVF treatment provides robust and comprehensive effects for improving CNS damage. Additionally, these mechanisms may translate and help explain the favorable effects with current clinical applications such as cell-assisted liposuction that uses SVF cells for improving fat grafting yet mechanisms are still unclear. / 1 / Annie C. Bowles

Currently, about one in every eight Americans is age 65 or older; by the year 2050, it will be one in five people. Given this “graying” of the population, research into successful aging is of increasing relevance. The question of how to precisely define successful aging, however, has not been completely answered. Likewise, the role of vascular risk factors, subclinical vascular brain damage, and other biopsychosocial characteristics in normal cognitive aging are not well understood. This Dissertation focused on the identification of some of the physiological, behavioral, and social risk factors that distinguish people able to maintain extraordinary health at an advanced age. Specifically, we aimed to create an ecologically valid definition of successful aging that incorporates both physical well-being and cognitive abilities, and to report the prevalence of successful cognitive aging in a population-based multi-ethnic cohort of older adults. We sought to describe how the prevalence varies by several sociodemographic and psychosocial determinants, and to investigate global vascular risk, depressive symptomatology, and MRI markers of subclinical vascular brain damage as correlates of successful cognitive aging. We observed the prevalence of successful cognitive aging to be 37% in the study sample (N=1,162) of a diverse racial/ethnic population in Northern Manhattan (NYC, NY). The prevalence decreased with increasing age; we did not observe any differences by racial/ethnic group, but did note a lower prevalence with lower socioeconomic status. Several social resources and self-reported quality of life were related to successful cognitive aging, and appeared more important than demographic variables alone. We found that the likelihood of successful cognitive aging decreases with increasing global vascular risk score, more severe depressive symptomatology, and greater white matter damage. The field of successful aging requires further study. Consideration of such biopsychosocial factors as socioeconomic status, social support, quality of life, and depressive symptoms alongside novel indicators of disease and disability including global vascular risk and white matter hyperintensity burden is essential. It may lead to a more robust definition of successful cognitive aging replete with opportunities to modify the aging process, as many of the factors investigated in this study are modifiable.

Vascular stents are medical devices used to treat stenoses blockages in arteries that restrict blood flow. Most commonly, stents are made out of stainless steel or nitinol, and are delivered to the afflicted sites via catheter-based delivery systems. Usually, stents are balloon-expandable or self-expanding. In order for the treated vessel to remain patent, it is necessary that the stents be oversized to prevent flow-induced or pressureinduced stent migration. Furthermore, stents must be rigid enough to prevent the collapse of the vessel, allowing the free passage of blood. However, it has been observed that the presence of the stent in the artery triggers adverse biological responses such as neointinal hyperplasia, often times culminating in restenosis. Extensive research external to this investigation has elucidated evidence to suggest that the abnormally high stresses imparted to the arterial wall as a result of stenting are an important factor in the treatment and development of cardiovascular diseases. Furthermore, normal physiologic diameter flcutuations between systole and diastole produce beneficial biological responses in the artery wall. The primary purpose of this study was to investigate specific stent design criteria that minimize the stress field in the arterial wall to mitigate the impact of restenosis. Commerically available finite element software was used to design the stents parametrically, and perform the stress analysis on a hyperelastic arterial model, including the effects of contact between the artery and stent. Seven stent geometries were uniquely defined by varying strut-spacing, ring amplitude, and crown radii of curvature. Stent designs with large strut spacing, large ring amplitude and a greater than zero radius of curvature imparted the less severe stress field in the arterial wall as well as maximizing vessel deflection between systole and diastole. In contrast, stents with small strut spacing, small amplitudes and zero radius of curvature at the crowns imparted significantly higher stresses. The small strut spacing and small amplitude created stiffer stents, prventing the artery from experiencing physiologic diameter fluctuations between systole and diastole. Evidence presented herein suggests that strut spacing should be as wide as possible without causing pillowing of the arterial wall into the stent.