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Orientadores: William Dias Belangero, Vanessa Petrilli Bavaresco Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas Resumo: Hidrogel de álcool de polivinil (PVA) foi utilizado como potencial reparador de defeitos osteocondrais da cartilagem articular. A citotoxicidade in vitro foi avaliada com células Vero e células-tronco mesenquimais da medula óssea de ratos Wistar-Kyoto. Para análise in vivo, os implantes foram colocados em defeitos produzidos nos joelhos de ratos Wistar. Após tempos de seguimento de 0, 3, 6, 12 e 24 semanas, as amostras foram analisadas por microscopia óptica convencional, ensaio mecânico de fluência à indentação, espectrometria de fluorescência raio X e microscopia eletrônica de varredura. Os resultados in vitro motraram que o hidrogel de PVA não afetou a atividade metabólica de ambas as células estudadas, nem tampouco a diferenciação osteogênica das células mesenquimais. Atividade da enzima fosfatase alcalina e formação de matriz mineralizada foram identificadas. O PVA implantado não apresentou sinais de desgastes ou qualquer mudança de aspecto quando comparado com o dia do implante. A interface do implante/tecido mostrou a formação e manutenção de tecido conjuntivo denso e osso recém-formado em todos os grupos estudados. Foi observado um aumento no módulo de fluência e concentração de cálcio e fósforo no PVA longo do tempo. O desempenho do higrogel de PVA irradiados e acetalizadas foi considerado satisfatório para a aplicação proposta Abstract: Irradiated and acetalized polyvinyl alcohol (PVA) hydrogel was investigated as a potential material for osteochondral defect repair in articular cartilage. The in vitro cytotoxicity of the material was evaluated with Vero cells and mesenchymal stem cells from bone marrow of Wistar-Kyoto rats. For in vivo analyses, plugs of the material were implanted into defects produced in the knees of male Wistar rats-WH. After follow-up times of 0, 3, 6, 12 and 24 weeks, the samples were analyzed by conventional optical and scanning electron microscopy, X-ray fluorescence spectrometry and submitted to mechanical testing of creep indentation. The in vitro results suggest that the PVA hydrogel did not affect the viability and morphology of any of the cell types studied. The hydrogel affected neither the metabolic activity of both studied cells nor the osteogenic differentiation of the mesenchymal cells. Activity of alkaline phosphatase and mineralized organic matrix formation could be identified. The implanted plugs showed no sign of wear or aspect change. The interface plug/tissue exhibited dense connective tissue and newly formed bone in all groups. It was observed an increase in the creep modulus and in the concentration of calcium and phosphorus in the PVA over time. The performance of the irradiated and acetalized PVA was considered satisfactory for the proposed application Mestrado Fisiopatologia Cirúrgica Mestre em Ciências

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Programa de Pós-Graduação em Biotecnologia e Biociências, Florianópolis, 2014.

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Agrárias, Programa de Pós-Graduação em Ciência dos Alimentos, Florianópolis, 2013. O objetivo deste trabalho foi desenvolver filmes poliméricos a base de álcool polivinílico incorporados com nanopartículas lipídicas sólidas contendo a-tocoferol e avaliar a possibilidade de seu uso como embalagens ativas antioxidantes para preservação de alimentos. As nanopartículas lipídicas contendo a-tocoferol foram preparadas pela técnica da homogeneização à alta pressão. A metodologia de superfície de resposta foi empregada para avaliar a influência das concentrações de a-tocoferol e dos surfactantes Lipoid S75 e Pluronic F68 sobre a recuperação total do a-tocoferol, diâmetro médio de partícula e potencial zeta, a fim de se obter condições ótimas para o preparo das nanopartículas. Foram também avaliadas a estabilidade das dispersões através do diâmetro médio de partícula, potencial zeta, índice de polidispersão e recuperação total do a-tocoferol pelo período de 21 dias em temperaturas de 6, 20 e 40 °C. A formulação ótima foi caracterizada quanto à morfologia das partículas e através de análises de raios-X e calorimetria exploratória diferencial. As condições ótimas para a encapsulação do a-tocoferol foram obtidas com 1,1% (m/v) de a-tocoferol, 0,75% (m/v) de Lipoid S75 e 1,3% (m/v) de Pluronic F68, com valores experimentais de 75,4%, 214,5 nm e -41,9 mV para recuperação total do a-tocoferol, diâmetro médio de partícula e potencial zeta, respectivamente. Esta preparação foi estável durante 21 dias de estocagem a 6 C°. O lipídeo sólido (behenato de glicerila) modificou sua natureza cristalina da forma ß' polimórfica em sua forma pura para a e ß' polimórfica na forma de nanopartícula. Os filmes de álcool polivinílico foram desenvolvidos pela técnica de casting com a adição de três diferentes proporções de nanopartículas e foram caracterizados através de análise de fluorescência, transmissão de luz e opacidade, atividade antioxidante, liberação do a-tocoferol em etanol 95%, bem como morfologia, espectroscopia no infravermelho, raios-X, propriedades térmicas, propriedades mecânicas e ângulo de contato. A adição de nanopartículas nos filmes de álcool polivinílico diminuiu significativamente a tensão na ruptura, o módulo de elasticidade e a elongação e aumentou a espessura dos mesmos, tornando os filmes menos rígidos e elásticos. Os filmes com nanopartículas se apresentaram mais hidrofílicos quando comparados com o filme controle. Foram observadas alta atividade antioxidante e propriedades de barreira contra a luz UV e visível. Além disso, houve uma liberação rápida e sustendada do a-tocoferol para o simulador de alimentos. O espectro no infravermelho e as análises térmicas dos filmes mostraram que a incorporação das nanopartículas com antioxidante afetou a estrutura química dos filmes com o estabelecimento de novas ligações químicas e diminuição da cristalinidade. Abstract : The aim of this study was to develop polymeric films based on poly(vinyl alcohol) incorporated with solid lipid nanoparticles containing -tocopherol and evaluate the possibility of their use as antioxidativepackaging in food preservation. Lipid nanoparticles containing -tocopherol were prepared by homogenization at high pressure. Theresponse surface methodology was used to evaluate the influence of theconcentrations of -tocopherol and of the surfactants Lipoid S75 andPluronic F68 on -tocopherol recovery rate, mean particle size and zetapotential, in order to obtain optimal conditions for preparation ofnanoparticles. We also assessed the stability of dispersions from throughmean particle size, zeta potential, polydispersity index, and -tocopherolrecovery rate for 21 days at temperatures of 6, 20 and 40 °C. Theoptimal formulation was characterized as the morphology of theparticles and through x-ray analysis and differential scanningcalorimetry. The optimum conditions for the encapsulation of -tocopherol were obtained at 1.1% (w/v) of -tocopherol, 0.75% (w/v) ofLipoid S75 and 1.3% (w/v) of Pluronic F68, and the experimental valuesof 75.4%, 214.5 nm, and -41.9 mV for -tocopherol recovery rate, meanparticle size, and zeta potential, respectively. This preparation wasstable during 21 days of storage at 6 ° C. The solid lipid (glycerylbehenate) changed its crystalline nature of the 'polymorphic form in itspure form for and ' polymorphic form when nanoparticle. The poly(vinyl alcohol) films were developed by "casting" with the addition ofthree different ratios and the nanoparticles were characterized byfluorescence analysis, light transmission and opacity, antioxidantactivity, -tocopherol release in fat food simulant, as well asmorphology, infrared spectroscopy, X-ray, thermal properties,mechanical properties and contact angle. The addition of nanoparticlesinto films of poly (vinyl alcohol) significantly reduced stress, elasticmodulus, and elongation and increased the thickness, making the filmsless rigid and elastic. Films with nanoparticles showed more hydrophiliccompared to the control film. We observed a high antioxidant activityand barrier properties against UV and visible light. In addition, therewas a burst and sustained release of -tocopherol in the food simulant.The infrared spectrum and thermal analysis of the films showed thatincorporation of nanoparticles with antioxidant affected the chemicalstructure of the films with the establishment of new chemical bonds anddecreased crystallinity.

PURPOSE: This study was designed to compare baseline data and clinical outcome between patients with prostate enlargement/benign prostatic hyperplasia (PE/BPH) who underwent unilateral and bilateral prostatic arterial embolization (PAE) for the relief of lower urinary tract symptoms (LUTS). METHODS: This single-center, ambispective cohort study compared 122 consecutive patients (mean age 66.7 years) with unilateral versus bilateral PAE from March 2009 to December 2011. Selective PAE was performed with 100- and 200-μm nonspherical polyvinyl alcohol (PVA) particles by a unilateral femoral approach. RESULTS: Bilateral PAE was performed in 103 (84.4 %) patients (group A). The remaining 19 (15.6 %) patients underwent unilateral PAE (group B). Mean follow-up time was 6.7 months in group A and 7.3 months in group B. Mean prostate volume, PSA, International prostate symptom score/quality of life (IPSS/QoL) and post-void residual volume (PVR) reduction, and peak flow rate (Qmax) improvement were 19.4 mL, 1.68 ng/mL, 11.8/2.0 points, 32.9 mL, and 3.9 mL/s in group A and 11.5 mL, 1.98 ng/mL, 8.9/1.4 points, 53.8 mL, and 4.58 mL/s in group B. Poor clinical outcome was observed in 24.3 % of patients from group A and 47.4 % from group B (p = 0.04). CONCLUSIONS: PAE is a safe and effective technique that can induce 48 % improvement in the IPSS score and a prostate volume reduction of 19 %, with good clinical outcome in up to 75 % of treated patients. Bilateral PAE seems to lead to better clinical results; however, up to 50 % of patients after unilateral PAE may have a good clinical outcome.

Purpose To evaluate whether prostatic arterial embolization (PAE) might be a feasible procedure to treat lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH). Materials and Methods Fifteen patients (age range, 62–82 years; mean age, 74.1 y) with symptomatic BPH after failure of medical treatment were selected for PAE with nonspherical 200-μm polyvinyl alcohol particles. The procedure was performed by a single femoral approach. Technical success was considered when selective prostatic arterial catheterization and embolization was achieved on at least one pelvic side. Results PAE was technically successful in 14 of the 15 patients (93.3%). There was a mean follow-up of 7.9 months (range, 3–12 months). International Prostate Symptom Score decreased a mean of 6.5 points ( P = .005), quality of life improved 1.14 points ( P = .065), International Index of Erectile Function increased 1.7 points ( P = .063), and peak urinary flow increased 3.85 mL/sec ( P = .015). There was a mean prostate-specific antigen reduction of 2.27 ng/mL ( P = .072) and a mean prostate volume decrease of 26.5 mL ( P = .0001) by ultrasound and 28.9 mL ( P = .008) by magnetic resonance imaging. There was one major complication (a 1.5-cm 2 ischemic area of the bladder wall) and four clinical failures (28.6%). Conclusions In this small group of patients, PAE was a feasible procedure, with preliminary results and short-term follow-up suggesting good symptom control without sexual dysfunction in suitable candidates, associated with a reduction in prostate volume.

Os autores relatam pela primeira vez utilização de uma nova partícula para embolização, constituída de um núcleo de acetato de polivinil revestido por polivinil-álcool, de forma esférica (Spherus®-First Line Brasil), como preparo pré-operatório em três pacientes portadores de neoplasia renal, na intenção de diminuir o tamanho do tumor e prevenir complicações hemorrágicas durante o ato operatório. Estas novas partículas foram projetadas e elaboradas nos laboratórios da COPPE/UFRJ. A embolização intra-arterial pré-operatória com estas novas partículas ocasionou acentuada isquemia em todo o tecido tumoral facilitando o procedimento cirúrgico. The authors report a brand new component for embolization composed by a polivinil acetate core and a polivinil-alcohol coat in a microspherical form ( Spherus®-First Line Brasil) used as preoperative management in three patients with renal tumors in an attempt to reduce the size of the tumors and to avoid hemorrhagic complications during the operations. This new component was developed in COPPE/UFRJ laboratories. The preoperative arterial embolization with this new component caused strong ischemia in the tumor tissue , facilitating the operative procedure.

Os autores relatam um caso de tumor de corpo carotídeo (paraganglioma) em um paciente de 74 anos de idade, submetido a embolização intra-arterial com micropartículas esféricas, de polivinil acetato, com casca de polivinil álcool (PVAc + PVA), previamente à ressecção do tumor. O estudo angiográfico demonstrou massa altamente vascularizada na bifurcação carotídea esquerda, sendo a embolização pré-operatória utilizada no intuito de diminuir a vascularização e reduzir a perda sangüínea, aumentando a segurança do tratamento cirúrgico. O estudo histopatológico confirmou a presença de trombose e isquemia tecidual. The authors report a case of carotid body tumor (paraganglioma) in a 74-year-old male patient, submitted to intraarterial embolization with spherical core/shield polyvinyl acetate and polyvinyl alcohol (PVAc + PVA) microparticles prior to surgical excision. Angiography has demonstrated a highly vascularized mass in the left carotid bifurcation, and preoperative embolization was used in order to decrease vascularity, reduce blood loss and improve safety of surgical treatment. Microscopic study confirmed presence of thrombosis and tissue ischemia.

OBJETIVO: Avaliar as características e os efeitos de um agente embólico, disponível comercialmente, consistindo de Polivinil Álcool (PVA) de morfologia flocular, e comparar com um agente esférico, de tecnologia nacional, consistindo de Polivinil Álcool e Polivinil Acetato (PVA + PVAc). MÉTODO: Foram utilizadas fêmeas de coelho albino "New Zealand", submetidas à embolização arterial renal. PVA-flocular foi usado em 24 animais, assim como PVA+PVAc-esférico. Seis animais foram utilizados como controle. Todos foram mantidos em cativeiro até a morte, por períodos pós-operatórios de 48 horas, cinco dias, 10 dias e 30 dias. RESULTADOS: Ambos os agentes promoveram oclusão do vaso e infarto do órgão. O estudo microscópico inicial das artérias embolizadas com PVA-flocular, mostra oclusão com trombo e PVA. Os vasos embolizados com PVA+PVAc-esférico, mostram os agentes ocupando praticamente todo o lúmen. No estudo de 30 dias, observa-se absorção do trombo e retração dos agentes de PVAflocular, criando espaços. E com PVA+PVAc-esférico, pode-se observar os agentes circundados por intensa fibrose. CONCLUSÕES: Ambas as partículas foram efetivas para causar isquemia tecidual. A reação inflamatória foi mais intensa com PVA+PVAc-esférico que também apresentou grau de penetração maior no sistema vascular. BACKGROUND: To evaluate the characteristics and the effects of an embolic agent, available commercially, consisting of irregular - Polyvinyl Alcohol (PVA), and to compare with a spherical agent, of brazilian technology, consisting of Polyvinyl Alcohol and Polyvinyl Acetate (PVA + PVAc). METHODS: Renal arterial embolization was performed in females of New Zealand White rabbits. Irregular - PVA was used in 24 animals. Spherical - PVA+PVAc was used in 24 animals. Six animals were used as control. All animals were maintained in captivity until the euthanasia, after 48 hours, 5 days, 10 days and 30 days. RESULTS: Both agents resulted in vessel occlusion and organ infarction. The initial macroscopic study of the arteries embolized with irregular-PVA, the occluding plug consisted of thrombus and PVA. In vessels embolized with spherical-PVA+PVAc, the occluding plug consisted mostly of the embolic agent. After 30 days, there is absorption of the thrombus and retraction of the agents of PVA-irregular, creating spaces. With spherical-PVA+PVAc, it can be observed the agents surrounded by intense fibrosis. CONCLUSION: Both particles were effective to cause tissue ischemia. The inflammatory reaction was more intense with spherical-PVA+PVAc, besides presenting larger degree of penetration in the vascular system.