Substitutos ósseos são estudados com a finalidade de encontrar biomateriais que apresentem características semelhantes ao enxerto ósseo autógeno e que tenham facilidade para o seu uso. Em busca desses biomateriais, os vidros bioativos têm sido pesquisados demonstrando propriedades de osteoindução e osteocondução. Este estudo avalia o reparo ósseo associado ao emprego de vidros bioativos diferentes taxas de pentóxido de nióbio 3mol% e 10mol%, comparados ao enxerto ósseo autógeno. A amostra foi composta por 52 ratos aleatoriamente agrupados em quatro tempos experimentais (15, 30, 60, 90 dias pós-operatórios). Três cavidades cirúrgicas foram confeccionadas na diáfise femural direita, preenchidas randomicamente com o enxerto ósseo autógeno e as duas composições de vidros bioativos contendo pentóxido de nióbio. Avaliou-se através de análise histológica, microscopia eletrônica de varredura, microtomografia computadorizada e espectroscopia de micro-Raman. Os resultados mostraram reparo ósseo em estágio avançado pela análise histológica e diferenças significativas (P=0.0017) entre o volume ósseo para o grupo de vidro bioativo composto por 3mol% de nióbio, evidência de incorporação dos biomateriais ao tecido ósseo neoformado pela análise de superfície e alta concentração de fosfato verificada em período precoce nos grupos de vidros bioativos. Tais achados mostraram que os vidros bioativos avaliados apresentaram propriedades de osteocondução e osteoindução. / Bone substitutes are studied in order to find biomaterials that exhibit characteristics similar to autogenous bone graft and have easy to use. In pursuit of these biomaterials, bioactive glasses have been researched demonstrating osteoinductive and osteoconductive properties. This study evaluates bone healing associated with the use of bioactive glasses containing different rates of niobium pentoxide 3mol% and 10mol%, compared to autogenous bone graft. The sample consisted of 52 rats randomly grouped into four times (15, 30, 60, 90 postoperative days). Three surgical cavities were prepared in the right femoral shaft, randomly filled with autogenous bone graft and two compositions of bioactive glasses containing niobium pentoxide. It was evaluated by histological analysis, scanning electron microscopy, computed microtomography and micro-Raman spectroscopy. The results showed bone healing at an advanced stage by histological analysis and significant differences (P = 0.0017) between bone volume to the bioactive glass group of 3mol% niobium, evidence of incorporation of biomaterials to the newly formed bone tissue for surface analysis and High concentration checked phosphate at an earlier period in the groups of bioactive glasses. These findings showed that the evaluated bioactive glasses showed osteoconductive and osteoinductive property.

The motor symptoms of Parkinson's disease (PD) have been linked to the emergence of exaggerated oscillatory activity in the 13 - 35 Hz beta range in recordings of the basal ganglia (BG) thalamocortical circuit of PD patients and animal models. PD patients and animal models also express dopamine-dependent cognitive impairments, implying effects of dopamine loss on the function of the anterior cingulate cortex (ACC). This thesis examines the electrophysiological behavior of the BG thalamocortical circuit in PD and dopamine-normal states during cognitive and motor activity. In vivo recordings in the BG of PD and dystonic patients were used to study the influence of dopamine during a test of executive function. Normal executive function was also investigated in the dopamine-healthy ACC of chronic pain patients. Both the BG and ACC exhibited lateralized electrophysiological responses to feedback valence. The BG also exhibited dopamine-sensitive event-related behavior. In additional experiments, chronically implanted recording electrodes in awake, behaving hemiparkinsonian rats were used to examine the transmission of synchronized oscillatory activity from the BG, through the ventral medial (VM) thalamus, to the ACC. Modulation of subthalamic nucleus, VM thalamus, and ACC activity during a simple cognitive/movement task was also investigated in hemiparkinsonian rats. Findings in the rat model suggest that ACC-mediated executive function is dopamine-sensitive and is reflected in the region's electrophysiology. These results may provide further insight into the significance of excessive oscillatory activity in PD and its influence on cognitive systems.

abstract: Extremely thick cranial vaults have been noted as a diagnostic characteristic of Homo erectus since the first fossil of the species was identified, but potential mechanisms underlying this seemingly unique trait have not been rigorously investigated. Cranial vault thickness (CVT) is not a monolithic trait, and the responsiveness of its layers to environmental stimuli is unknown. Identifying factors that affect CVT would be exceedingly valuable in teasing apart potential contributors to thick vaults in the Pleistocene. Four hypotheses were tested using CT scans of skulls of more than 1100 human and non-human primates. Data on total frontal, parietal, and occipital bone thickness and bone composition were collected to test the hypotheses: H1. CVT is an allometric consequence of brain or body size. H2. Thick cranial vaults are a response to long, low cranial vault shape. H3. High masticatory stress causes localized thickening of cranial vaults. H4. Activity-mediated systemic hormone levels affect CVT. Traditional comparative methods were used to identify features that covary with CVT across primates to establish behavior patterns that might correlate with thick cranial vaults. Secondly, novel experimental manipulation of a model organism, Mus musculus, was used to evaluate the relative plasticity of CVT. Finally, measures of CVT in fossil hominins were described and discussed in light of the extant comparative and experimental results. This dissertation reveals previously unknown variation among extant primates and humans and illustrates that Homo erectus is not entirely unique among primates in its CVT. The research suggests that it is very difficult to make a mouse grow a thick head, although it can be genetically programmed to have one. The project also identifies a possible hominin synapomorphy: high diploë ratios compared to non-human primates. It also found that extant humans differ from non-human primates in overall pattern of which cranial vault bones are thickest. What this project was unable to do was definitively provide an explanation for why and how Homo erectus grew thick skulls. Caution is required when using CVT as a diagnostic trait for Homo erectus, as the results presented here underscore the complexity inherent in its evolution and development. / Dissertation/Thesis / Ph.D. Anthropology 2012

Estudos prévios sugerem que a modificação da superfície de uma hidroxiapatita sinterizada, através do condicionamento ácido, favorece a interação deste biomaterial com o organismo. Este estudo avaliou o reparo de defeitos ósseos preenchidos por hidroxiapatita sinterizada modificada (HAM), taxa Ca/P = 1.5 e hidroxiapatita sinterizada pura (HA), taxa Ca/P = 1.67, em um modelo experimental in vivo. Foram utilizados 52 ratos, submetidos à confecção de defeitos ósseos que promoveram as exposições das raízes mesiais dos primeiros molares superiores, sendo utilizado implante de HAM no lado direito e, como controle, HA no lado esquerdo. Os animais foram distribuídos randomicamente em quatro tempos pós-operatórios (15, 30, 60 e 90 dias). Após a morte dos animais, as peças foram preparadas e avaliadas através de análise histológica, microscopia eletrônica de varredura (MEV) e microtomografia computadorizada (MicroCT). Os resultados mostraram maior neoformação óssea associada à HAM (p=0.009). Na análise longitudinal a HAM apresentou neoformação óssea superior no tempo experimental de 90 dias pós-operatório comparado aos tempos de 15 e 30 dias pós-operatórios (p=0.014 e p=0.018 respectivamente). Para os parâmetros atividade osteoclástica e processo inflamatório não foram observadas diferenças estatisticamente significativas entre HAM e HA (p=0.446 e p=0.411, respectivamente). As avaliações através da MicroCT demonstraram aumento da densidade óssea ao longo dos tempos experimentais para a HAM (p=0.0042), mas não para HA (p=0.356). A microscopia eletrônica de varredura permitiu a observação das microporosidades associadas à HAM e a incorporação dos biomateriais ao tecido ósseo. Nas condições experimentais desse estudo, a aplicação de HAM resulta em melhor reparo ósseo, quando comparada a HA. / Previous studies suggest that modifying the surface of a sintered hydroxyapatite (HA) through acid-etching favors the interaction between the biomaterial and organism. This study evaluated bone repair of defects filled with a modified sintered hydroxyapatite (HAM; Ca/P ratio = 1.5), and sintered hydroxyapatite (HA; Ca/P ratio = 1.67), in an experimental model in vivo. Bone defects were created to promote mesial roots exposure of superior first molars in 52 rats. HAM implant was put into the right side bone defect and HA was used on the left side, as control. Animals were randomized into four postoperative groups (15, 30, 60 and 90 days) and killed, respectively, in each time. Surgical pieces were prepared and essessed by histological analysis, scanning electron microscopy (SEM) and computed microtomography (MicroCT). The results showed increased bone formation associated with HAM (p = 0.009). Higher bone formation was related to HAM at 90 days postoperative compared to 15 and 30 days after surgery (p = 0.014 and p = 0.018, respectively). No statistically significant differences were found between HAM and HA for osteoclastic activity and inflammation (p = 0.446 and p = 0.411, respectively). MicroCT showed increased bone density throughout the experimental periods for the HAM (p = 0.0042), but not for HA (p = 0 356). Scanning electron microscopy allowed the observation of microporosities associated with HAM and the incorporation of biomaterials in bone tissue. Under the experimental conditions of this study, the application of HAM results in better bone healing compared to HA.

Substitutos ósseos são estudados com a finalidade de encontrar biomateriais que apresentem características semelhantes ao enxerto ósseo autógeno e que tenham facilidade para o seu uso. Em busca desses biomateriais, os vidros bioativos têm sido pesquisados demonstrando propriedades de osteoindução e osteocondução. Este estudo avalia o reparo ósseo associado ao emprego de vidros bioativos diferentes taxas de pentóxido de nióbio 3mol% e 10mol%, comparados ao enxerto ósseo autógeno. A amostra foi composta por 52 ratos aleatoriamente agrupados em quatro tempos experimentais (15, 30, 60, 90 dias pós-operatórios). Três cavidades cirúrgicas foram confeccionadas na diáfise femural direita, preenchidas randomicamente com o enxerto ósseo autógeno e as duas composições de vidros bioativos contendo pentóxido de nióbio. Avaliou-se através de análise histológica, microscopia eletrônica de varredura, microtomografia computadorizada e espectroscopia de micro-Raman. Os resultados mostraram reparo ósseo em estágio avançado pela análise histológica e diferenças significativas (P=0.0017) entre o volume ósseo para o grupo de vidro bioativo composto por 3mol% de nióbio, evidência de incorporação dos biomateriais ao tecido ósseo neoformado pela análise de superfície e alta concentração de fosfato verificada em período precoce nos grupos de vidros bioativos. Tais achados mostraram que os vidros bioativos avaliados apresentaram propriedades de osteocondução e osteoindução. / Bone substitutes are studied in order to find biomaterials that exhibit characteristics similar to autogenous bone graft and have easy to use. In pursuit of these biomaterials, bioactive glasses have been researched demonstrating osteoinductive and osteoconductive properties. This study evaluates bone healing associated with the use of bioactive glasses containing different rates of niobium pentoxide 3mol% and 10mol%, compared to autogenous bone graft. The sample consisted of 52 rats randomly grouped into four times (15, 30, 60, 90 postoperative days). Three surgical cavities were prepared in the right femoral shaft, randomly filled with autogenous bone graft and two compositions of bioactive glasses containing niobium pentoxide. It was evaluated by histological analysis, scanning electron microscopy, computed microtomography and micro-Raman spectroscopy. The results showed bone healing at an advanced stage by histological analysis and significant differences (P = 0.0017) between bone volume to the bioactive glass group of 3mol% niobium, evidence of incorporation of biomaterials to the newly formed bone tissue for surface analysis and High concentration checked phosphate at an earlier period in the groups of bioactive glasses. These findings showed that the evaluated bioactive glasses showed osteoconductive and osteoinductive property.

Submitted by Maria Anália Conceição (marianaliaconceicao@gmail.com) on 2016-06-28T13:08:11Z No. of bitstreams: 1 Publico-NOVO-24.pdf: 1515165 bytes, checksum: 3b9206d6518639a99202f8ee9c5f29ad (MD5) / Approved for entry into archive by Maria Anália Conceição (marianaliaconceicao@gmail.com) on 2016-06-28T13:15:12Z (GMT) No. of bitstreams: 1 Publico-NOVO-24.pdf: 1515165 bytes, checksum: 3b9206d6518639a99202f8ee9c5f29ad (MD5) / Made available in DSpace on 2016-06-28T13:15:12Z (GMT). No. of bitstreams: 1 Publico-NOVO-24.pdf: 1515165 bytes, checksum: 3b9206d6518639a99202f8ee9c5f29ad (MD5) Previous issue date: 2015 / Introdução: A tolerância cutânea à radiação é o principal fator limitante da radioterapia. A escassez de estudos experimentais é imensa, principalmente em animais de médio porte, como os coelhos. Objetivo: Descrever um modelo experimental de radiodermatite em coelhos Métodos: Neste estudo foram utilizados 24 coelhos da raça Nova Zelândia, machos, com 6 meses de idade, peso médio de 2,5 Kg. Os mesmos foram distribuídos em 4 grupos (n=6 para cada grupo), sendo um grupo controle (sem nenhuma intervenção) e os demais submetidos à radioterapia com sessão única de 10, 20 e 30 Gy, respectivamente. Foram realizadas análises fotográficas e histopatológicas das áreas irradiadas. Resultados: Os animais do grupo controle após 30 dias da epilação apresentaram crescimento dos fâneros regularmente. Os animais do grupo 20 Gy e 30 Gy apresentaram alopecia com duração de 60 dias e 90 dias, respectivamente. A partir do dia 30, a área irradiada dos animais do grupo 30 Gy apresentou grau 3 e 4 de radiodermatite, persistindo por 90 dias. A redução progressiva da contagem de anexos, vasos sanguíneos e um aumento da deposição de colágeno foi significante, quando comparado o o grupo controle com o grupo de 30 Gy. Conclusão: A dosagem de 30 Gy é a mais eficaz para este modelo experimental de radiodermatite. / Introduction: The cutaneous tolerance is a limiting factor for this oncologic treatment. The lack of experimental models is enormous, primarily for mid size animals, such as rabbits. Purpose: Describe an experimental model of cutaneous radiation injury in rabbits Methods: On this study 24 six-month-old New Zealand male rabbits, with an average weight of 2.5kg, were used. They were distributed in 4 groups (n=6 per group). The control group did not receive radiotherapy and the others received one radiotherapy session of 10, 20 and 30Gy, respectively. Photographic analysis and histopathological evaluation of the irradiated areas were carried out. Results: After 30 days, the animals from the control group had all their hair grown. In spite of that, the animals from group 20Gy had a 60-day alopecia and from group 30Gy, a 90-day alopecia. After the 30th day, the 30Gy group demonstrated 90-day cutaneous radiation injuries, graded 3 and 4. A progressive reduction of glands and blood vessels count and an increase on collagen deposition was significant, when the control group is compared to the group 30Gy. Conclusion: This study demonstrates the dosage 30Gy is the most effective for this experimental model of cutaneous radiation injury in rabbits.

Stroke is a leading cause of neurological disability, often resulting in long-term motor impairments due to damage to the striatum and/or motor cortex. While both humans and animals show spontaneous recovery following stroke, little is known about how the injury location affects recovery and what causes recovery to plateau. This information is essential in order to improve current rehabilitation practice and develop new therapies to enhance recovery. In this thesis, we used endothelin-1 (ET-1), a potent vasoconstrictor, to produce focal infarcts in the forelimb motor cortex (FMC), the dorsolateral striatum (DLS) or both the FMC and DLS in male Sprague-Dawley rats. In the first experiment, the spontaneous recovery profile of animals was followed over an 8-week period using multiple behavioural tasks assessing motor function and limb preference to identify how recovery varies depending on injury location. Infarct volumes were measured to determine the association between injury and behavioural outcome. All three groups had significant functional impairments on the Montoya staircase, beam traversal, and cylinder tests following stroke, with the combined group having the largest and most persistent impairments. Importantly, spontaneous recovery was not simply dependent on lesion volume but on the lesion location and the behavioural test employed. In the second experiment, we focused on a potential cellular mechanism thought to underlie post-stroke plasticity and functional recovery. In a separate cohort of animals, we assessed how plasticity-limiting perineuronal nets (PNNs) and associated parvalbumin-positive (PV) GABAergic interneurons change following similar ET-1 strokes as in the prior experiment. A significant reduction in the density of PNNs was observed in the perilesional cortex of animals that received a cortical-only or combined stroke but not a striatal-only injury. Although there were no significant differences in the density of PV interneurons between sham and stroked groups, a significant negative correlation existed between cortical infarct volume and the density of PV interneurons in the perilesional cortex. Taken together these results demonstrate that lesion location influences motor recovery and neuroplastic changes following stroke. This supports the idea that a “one size fits all” approach for stroke rehabilitation may not be effective and treatment needs to be individualized to the patient.

abstract: Social influences are important determinants of drug initiation in humans, particularly during adolescence and early adulthood. My dissertation tested three hypotheses: 1) conditioned and unconditioned nicotine and social rewards elicit unique patterns of neural signaling in the corticolimbic neurocircuitry when presented in combination versus individually; 2) play behavior is not necessary for expression of social reward; and 3) social context enhances nicotine self-administration. To test the first hypothesis, Fos protein was measured in response to social and nicotine reward stimuli given alone or in combination and in response to environmental cues associated with the rewards in a conditioned place preference (CPP) test. Social-conditioned environmental stimuli attenuated Fos expression in the nucleus accumbens core. A social partner elevated Fos expression in the caudate-putamen, medial and central amygdala, and both nucleus accumbens subregions. Nicotine decreased Fos expression in the cingulate cortex, caudate-putamen, and the nucleus accumbens core. Both stimuli combined elevated Fos expression in the basolateral amygdala and ventral tegmental area, suggesting possible overlap in processing both rewards in these regions. I tested the second hypothesis with an apparatus containing compartments separated by a wire mesh barrier that allowed limited physical contact with a rat or object. While 2 pairings with a partner rat (full physical contact) produced robust CPP, additional pairings were needed for CPP with a partner behind a barrier or physical contact with an object (i.e., tennis ball). The results demonstrate that physical contact with a partner rat is not necessary to establish social-reward CPP. I tested the third hypothesis with duplex operant conditioning chambers separated either by a solid or a wire mesh barrier to allow for social interaction during self-administration sessions. Nicotine (0.015 and 0.03 mg/kg, IV) and saline self-administration were assessed in male and female young-adult rats either in the social context or isolation. Initially, a social context facilitated nicotine intake at the low dose in male rats, but suppressed intake in later sessions more strongly in female rats, suggesting that social factors exert strong sex-dependent influences on self-administration. These novel findings highlight the importance of social influences on several nicotine-related behavioral paradigms and associated neurocircuitry. / Dissertation/Thesis / Doctoral Dissertation Psychology 2015

As lesões das veias justa-hepáticas apresentam mortalidade elevada apesar das diferentes técnicas cirúrgicas de tratamento. Os objetivos desse estudo são: a) construir um modelo experimental de lesão letal transfixante de veia cava inferior (VCI) justa-hepática por técnica endovascular, e avaliar as alterações hemodinâmicas decorrentes dessa lesão. b) tratar a lesão por meio de reposição volêmica inicial e controle do sangramento com a colocação de endoprótese revestida (ER), c) acompanhar clinicamente o pós-operatório com ultra-som Doppler (USD) e cavografia. d) avaliar as alterações anatomopatológicas da VCI com a ER. Vinte cães anestesiados e monitorados [freqüência cardíaca (FC), pressão arterial média (PAM), pressão na VCI, pressão vesical, pressão peritoneal] foram submetidos a lesão transfixante da VCI justa-hepática, por técnica endovascular. Após a reposição volêmica inicial foram divididos em dois grupos: controle (GI)) e experimento (GII). O GI ficou em observação e quando a PAM atingiu níveis entre 40 e 30 mm Hg foi submetido a laparotomia para avaliação do sangramento e da lesão. O GII foi tratado com ER e acompanhado clinicamente com USD e cavografia após 4 (GIIA) e 8 semanas (GIIB) quando foram sacrificados e a VCI com ER foi analisada. O GI apresentou aumento significativo das pressões peritoneal, vesical e da VCI, hipotensão arterial, bradicardia e óbito após 80 minutos. No GII a sobrevida foi de 100%, sem repercussões clínicas. O USD e a cavografia mostraram que todas as ERs encontravam-se pérvias. O Doppler revelou padrão de fluxo monofásico pulsátil nos segmentos estudados. Ao US, as medidas dos diâmetros da ER nas 2ª (7,89 ± 1,20 mm), 4ª (7,24 ± 1,72 mm) e 8ª (8,04 ±1,15 mm) semanas, não mostraram diferenças estatísticas significantes. Na cavografia as medidas dos diâmetros da VCI antes da colocação da ER, logo após a sua colocação e após 4 e 8 semanas, não mostraram diferenças estatisticamente significantes entre os GIIA e GIIB. Esses dados analisados para o GII como um todo, mostram diferenças estatisticamente significantes; VCI (11,74 ± 0,86 mm) T=1,00 p= 0,007, após a colocação da ER (12,86 ± 0,41 mm) T= 0,00 p= 0,008 e no período tardio (8,44 ± 2,00 mm) T= 0,00 p= 0,005. A média da taxa de redução do diâmetro da luz da ER foi de 27,43 ± 20,00%. As medidas, em cm de H2O, da pressão na VCI, cranial (0,55 ± 0,50), caudal (1,15 ± 1,76) e no interior da ER (0,75 ± 0,63), não mostraram diferenças estatisticamente significantes. No estudo da VCI com ER, observamos a formação de neoíntima mais espessa do que às camadas média e íntima. Na área da lesão, a camada média estava seccionada e cicatrizada por tecido fibroconjuntivo. Concluindo, a) criamos um modelo experimental de lesão letal transfixante de VCI justa-hepática por técnica endovascular com mortalidade de 100% dos casos após 80 minutos da lesão, provocando hemoperitônio volumoso com aumento significante da pressão peritoneal, b) tratamos essa lesão com ER com sobrevida de 100%, c) verificamos através do USD e cavografia a perviedade da ER após 2, 4 e 8 semanas do tratamento, d) observamos espessamento significante da neoíntima com redução de 27% do diâmetro da luz, sem repercussão clínica ou aumento de gradiente pressórico / Juxtahepatic vein injuries present a high mortality rate despite the different surgical techniques for their treatment. The objectives of this study are: a) to develop an experimental model of transfixing lethal injury of the juxtahepatic inferior vena cava (IVC) through endovascular technique and to evaluate the hemodynamic alterations caused by this injury, b) to treat the lesion with initial volume replacement and hemorrhage control with the insertion of a stent graft (SG), c) to clinically follow the posttreatment period with Doppler ultrasound (DUS) and cavography, d) to evaluate the anatomopathological alterations of the IVC with the SG. Twenty anesthetized and monitored dogs [heart rate (HR), mean arterial pressure (MAP), vesical and, peritoneal pressure] were submitted to transfixing injury of the juxtahepatic IVC, by endovascular technique. After the initial volume replacement they were divided into two groups: control (GI) and experimental (GII). GI was maintained under observation and when MAP reached levels between 40 and 30 mm Hg the animals were submitted to laparotomy to evaluate bleeding and the lesion. GII was treated with SG and clinically followed by DUS and cavography after 4 (GIIA) and 8 weeks (GIIB), when they were sacrificed and IVC and SG were analyzed. GI presented a significant increase in peritoneal, vesical and IVC pressures, arterial hypotension, bradycardia, and death after 80 minutes. GII had a 100% survival rate, without clinical repercussions. DUS and cavography showed that all SG were patent. Doppler ultrasound showed a pattern of a monophasic pulsatile flux in all studied segments. On US, the measures of SG diameters in the 2nd (7.89 ± 1.20mm), 4th (7.24 ± 1.72mm) and 8th (8.04 ± 1.15mm) weeks did not show statistically significant differences. On cavography the measures of IVC diameters before the insertion of SG, immediately after its insertion and after 4 and 8 weeks did not show statistically significant differences between GIIA and GIIB. These data analyzed for the GII as a whole, showed statistically significant differences; IVC (11.74 ± 0.86mm) T=1.00 p=0.007, after the insertion of SG (12.86 ± 0.41mm) T=0.00 p=0.008 and in the late period (8.44 ± 2.00mm) T=0.00 p=0.005. The average rate of reduction in lumen diameter of SG was 27.43 ± 20,00%. The measures, in H2O cm of the IVC pressure, cranial (0.55 ± 0.50), caudal (1.15 ± 1.76) and in the interior of the SG (0.75 ± 0.63) did not show statistically significant differences. In the IVC study with SG, we observed the formation of a thicker neointima as compared to the media and intima layers. In the area of the lesion, the media layer was injured and cicatrized with fibroconjuctive tissue. In conclusion, a) we created an experimental model of transfixing lethal injury of the juxtahepatic IVC by endovascular technique with a mortality rate of 100% after 80 minutes of the injury, causing an important hemoperitonium with significant increase in peritoneal pressure, b) we treated this lesion with SG, with a survival rate of 100%, c) we verified through DUS and cavography the patency of the SG after 2, 4 and 8 weeks of treatment, and d) we observed significant thickening of the neointima with a reduction of 27% in the diameter of the lumen, without clinical repercussion or pressure gradient increase

INTRODUÇÃO: O modelo eslastase-induzido de aneurismas tem se destacado, nos últimos anos, porque simula as características geométricas dos aneurismas intracranianos humanos. A elastase destrói as fibras elásticas e dilata as artérias. A papaína é uma enzima que ainda não foi usada com esta finalidade. Os objetivos deste estudo foram determinar se a papaína produz aneurismas saculares em coelhos, e comparar suas características macroscópicas e histológicas com as dos aneurismas elastase-induzidos. MÉTODO: Dezoito coelhos brancos Nova Zelândia (1,9-3,2 kg) foram divididos em 3 grupos: I- elastase (n=7), II- papaína (n=8) e III- cirurgia controle (n=3). Os animais foram submetidos à exposição cirúrgica do pescoço, sendo que a artéria carótida comum direita foi usada como teste e a artéria carótida comum esquerda como controle. No 21° dia após a cirurgia, os animais foram sacrificados para retirada das artérias, tomada de suas medidas e análise histológica. Considerou-se formação de aneurisma quando a artéria teste dilatou em relação ao seu controle. RESULTADOS: Não houve aneurismas no grupo cirúrgico controle. Houve formação de aneurismas nos grupos elastase (71,4%) e papaína (100%). A diferença do diâmetro das artérias testes e seus respectivos controles não foi significativa (p= 0,15) entre os grupos elastase (média= 1,2 ± 0,4mm) e papaína (média= 2,1 ± 0,4mm), embora houvesse tendência deste último à maior dilatação . A histologia demonstrou que a papaína produziu maior tendência à lesão endotelial, à trombose (p = 0,01) e à inflamação parietal do que a elastase. A análise da fibrose intimal foi prejudicada em 50% dos casos do grupo papaína devido à trombose acentuada. Não houve diferença significativa entre os grupos quanto ao espessamento parietal (p=0,81) e ao grau de destruição das fibras elásticas (p= 0,009). CONCLUSÕES: A papaína produz aneurismas com tamanhos semelhantes aos da elastase, contudo a papaína provoca maior lesão endotelial, maior trombose e maior inflamação do que a elastase / INTRODUCTION: The elastase-induced model of experimental saccular aneurysms has been relevant in the last years because it mimics the size and geometric features of human intracranial aneurysms. Elastase destroys the arterys elastic fibers and produces arterial enlargement. Papain enzyme is also elastolytic but it had not been tested on saccular aneurysms creation yet. The purpose of this study was determine if papain produces saccular aneurysms in rabbits and to compare its gross and microscopic features are with the elastaseinduced aneurysms. METHODS: Eighteen New Zealand white rabbits (1.9 kg 3,2 kg) were separated in 3 groups: 1) sham (n=3) 0,9% saline solution; papain (n=8) 17-40 U; elastase (n=7) 6-8 U. The animals underwent surgical exposure of the neck; the right common carotid artery (RCCA) was used as the test and the left common carotid artery (LCCA) as the control. On the 21st day after surgery, animals were sacrificed for removal of the arteries, measurements and histological analysis. We determine formation of aneurysm to occur when the test artery dilated compared to the control. RESULTS: The sham group didnt develop aneurysms. There was aneurysm formation in the elastase (71,4%) and papain (100%) groups. The difference of the diameter of the tests and their respective controls is not significant (p=0,15) between elastase (average = 1,2 ± 0,4 mm) and papain (average = 2,1 ± 0,4mm) groups although there was tendency of this last one to produce larger aneurysms. the and to thrombosis (p = 0,01) and to parietal inflammation than the elastase. The analysis of the intimal fibrosis was not possible in 50% of papain cases due to pronounced thrombosis. There was no significant difference between the groups regarding the parietal thickening (p = 0,81) and the degree of destruction of the elastic fibers (0,009). CONCLUSION: Papain creates saccular aneurysms with similar dimensions to elastase-induced aneurysms. The microscopic results indicated papain destroys more endothelial cells, produces more thrombosis and more inflammatory process than elastase