Made available in DSpace on 2015-04-14T13:35:29Z (GMT). No. of bitstreams: 1 438172.pdf: 1191521 bytes, checksum: 237c9b927e3f38af88fb5e0c217da2cf (MD5) Previous issue date: 2012-03-28 / Wound healing represents a dynamic physiological process initiated and influenced by many factors. Nanocrystalline silver have been demonstrated to have antimicrobial and anti-inflammatory properties, whereas papain is a proteolytic enzyme, which has been used in different formulations for wound treatment in clinics. Objectives This study was conducted to further evaluate the wound healing activity of nanocrystalline silver dressings as compared to that obtained with 2% papain gel, for the treatment of acute wounds in rats and the impact on VEGF expression. Forty-eight male Wistar rats were randomly divided into four groups. Group 1: treated with saline solution (NaCl 0.9%); group 2: treated with nanocrystalline silver; group 3: treated with the excipient gel; group 4: treated with 2% papain gel. A full-thickness wound of 1.5 x 1.5 cm? was excised from the back of the rats, under aseptic conditions and were anesthetized by a mixture of ketamine and xylazine. All the animals were evaluated on the 3rd, 6th, 9th, 12th and 15th days for wound-healing rating and histological evaluation and imunohistochemistry for VEGF. The statistical analysis was performed ANOVA, followed by Bonferroni s test. The group treated with the nanocrystalline silver dressing, showed a healing ratio superior, in all periods, when compared to control group and was the unique showing complete wound healing at 15 days of evaluation. The 2% papain gel group, a significantly higher wound healing rate was observed only at the 3th and the 6th days, but the wound showed a bleeding and decrease of wound healing ratio from the 9th day on. Histological evaluation showed a fully matured and compact granulation tissue on the nanocristaline silver group. The others groups displayed thickned epidermis, with extensive areas of inflammation. Evident immunopositivity for VEGF was also seen in the granulation tissue layer at the 9th day, the nanocrystalline silver group showed a higher VEGF expression in blood vessels, epidermal cells and granulation tissue. In this work, based on both the qualitative and the quantitative analysis, the nanocrystalline silver group showed a better wound healing effect in view of a rapid contraction of wound, compared with the others groups. Furthermore, we show for the first time that pro-healing activities of nanocrystalline silver dressings are likely associated to the modulation of VEGF expression. / O processo de cicatriza??o representa uma cascata de eventos din?micos iniciados e influenciados por diversos fatores. A prata nanocristalina tem demonstrado uma a??o antimicrobiana e anti-inflamat?ria em diversos estudos, enquanto a papa?na, al?m da a??o anti-inflamat?ria, ? usada no desbridamento de feridas, por ser uma enzima proteol?tica. A a??o da papa?na depende da sua concentra??o que varia de 1% a 10%. Esse estudo foi conduzido com o objetivo de avaliar a a??o da prata nanocristalina e da papa?na gel 2% sobre o processo de cicatriza??o em ratos e o impacto dessas subst?ncias sobre a express?o de VEGF. Foram randomizados 48 ratos Wistar em 4 grupos. Grupo 1: tratado com solu??o salina; grupo 2: tratado com prata nanocristalina; grupo 3: tratado com gel excipiente; grupo 4: tratado com papa?na gel a 2%. Foi realizado uma excis?o de espessura total no dorso do animal, medindo de 1,5 x 1,5 mm. Foi respeitada t?cnica ass?ptica rigorosa e o animal foi anestesiado com xilazina e quetamina por via intraperitoneal. Todos os animais foram avaliados no 3?, 6?, 9?, 12? e 15? dia. As les?es foram fotografadas e analisadas pelo Programa Image J para estimar a ?rea. Foram recolhidas amostras das les?es nos diferentes per?odos de avalia??o para an?lise histol?gica e imuno-histoquimica para VEGF. A an?lise estat?stica foi feita pelo teste de an?lise de vari?ncia (ANOVA), seguido pelo Teste de Bonferroni, utilizando programa Graphped 4. O grupo tratado com a prata nanocristalina, apresentou cicatriza??o completa ao final de 15 dias, diferente dos outros grupos. O grupo tratado com papa?na gel 2% apresentou uma maior taxa de cicatriza??o no 3? e 6? dia, que se manteve est?vel a partir do 9? dia. A avalia??o histol?gica mostrou um tecido de granula??o maduro no grupo da prata nanocristalina. Os outros grupos apresentaram uma epiderme espessa com extenso infliltrado inflamat?rio. Foi evidente a imunopositividade para VEGF no grupo da prata nanocristalina, principalmente no 9? dia de tratamento. Nesse trabalho, baseado tanto na an?lise quantitativa como qualitativa, o grupo tratado com prata nanocristalina mostrou uma melhor taxa de cicatriza??o, evidenciado por uma mais r?pida contra??o da ferida, comparada com os outros grupos. Al?m disso, evidenciamos que a a??o pr? cicatriza??o da prata nanocristalina est? associada com a modula??o da express?o de VEGF.

Made available in DSpace on 2015-04-14T13:35:30Z (GMT). No. of bitstreams: 1 438171.pdf: 6920524 bytes, checksum: f5e5c6d7e177dfd60f3b3303552cc797 (MD5) Previous issue date: 2012-03-28 / OBJECTIVE : To evaluate and compare the effect of using Platelet-Rich Plasma (PRP) and Platelet-Rich Fibrin (PRF) in the repair of the Achilles tendon (TA) of rats. MATERIAL and METHODS : Forty-eight adult male rats randomized into three experimental groups: PRP, PRF and Control (saline 0.9%). A 3 cm longitudinal incision was made in the right leg of each rat in order to expose the TA. Later, it was a break in the same horizontal, and the repair performed with suture Kessler-type, when the sequence was applied 50 &#956;L of the treatment in question. After 14 and 28 days postoperatively, the targeted part of the TA was removed, thus initializing the histological processing (Hematoxylin/Eosin; Sirius Red) to obtain results. The data obtained were expressed at 5% significance level (p <0.05) with mean ? SE. RESULTS : When comparing the three groups together, as to time and area of collagen type I and III, only statistical difference between the control group (16.22%) and the PRP group (37.16%) at 14 days after the treatment, no statistically significant difference was observed in the other groups. In the same way, when compared within groups of 14 and 28 days, the PRF group showed a significant difference for collagen I (27.76% and 47.74%) and III (66.94% and 46%) respectively. Control group showed significant difference in collagen type I (14.20% and 40.90%), not observed any significant difference in the PRP group. When evaluated on Hematoxylin/Eosin staining, PRP and control were similar in the times studied, differing only in the presence of hemorrhage, that was more expressed in the PRP group. Already the group PRF has shown to be more organized, especially in time of 28 days compared to the other two treatments. CONCLUSION : The data from this study suggest that the Platelet-Rich Fibrin tends to promote the accelerated regeneration of the Achilles tendon of rats, bringing promising prospects for future use in the clinic. / OBJETIVO : Avaliar e comparar o efeito do uso de plasma rico em plaquetas (PRP) e fibrina rica em plaquetas (PRF) no reparo do tend?o de Aquiles (TA) de ratos. MATERIAL e M?TODOS : Foram utilizados 48 ratos machos adultos distribu?dos randomicamente em tr?s grupos experimentais: PRP, PRF e Controle (solu??o salina 0,9%). Uma incis?o longitudinal de 3 cm foi realizada na perna direita de cada rato, a fim de expor o TA. Posteriormente, fez-se uma ruptura horizontal no mesmo, sendo a repara??o realizada com sutura do tipo Kessler, onde na seq??ncia foi aplicado 50 &#956;L do tratamento em quest?o. Passados 14 e 28 dias p?s- operat?rio, a parte segmentada do TA foi removida, inicializando assim o processo histol?gico (Hematoxilina/Eosina; Picros?rius Red) para obten??o de resultados. Os dados obtidos foram expressos ao n?vel de 5% de signific?ncia (p < 0.05) com m?dia ? EP. RESULTADOS : Ao comparar os tr?s grupos entre si, quanto ao tempo e ?rea de col?geno tipo I e III, houve diferen?a estat?stica somente entre o grupo Controle (16.22%) e o grupo PRP (37.16%) aos 14 dias ap?s o tratamento, n?o sendo observada diferen?a estatisticamente significativa nos outros grupos. Da mesma forma, quando comparados intra-grupos em 14 e 28 dias, o grupo PRF apresentou diferen?a significativa para col?geno I (27.76% e 47.74%) e III (66.94% e 46%) respectivamente. Grupo Controle demonstrou diferen?a significativa para col?geno tipo I (14.20% e 40.90%), n?o sendo observada qualquer diferen?a significativa no grupo PRP. Quando avaliados na colora??o Hematoxilina e Eosina, PRP e Controle apresentaram-se semelhantes nos tempos avaliados, diferindo apenas quanto a presen?a de hemorragia, que foi mais expressa no grupo PRP. J? o grupo PRF demonstrou-se mais organizado, principalmente no tempo de 28 dias quando comparado aos outros dois tratamentos. CONCLUS?O : Os dados obtidos neste trabalho sugerem que a Fibrina Rica em Plaquetas tem tend?ncia a promover a regenera??o acelerada do tend?o de Aquiles de ratos, trazendo perspectivas promissoras para futuras utiliza??es na cl?nica.

Made available in DSpace on 2015-04-14T13:35:31Z (GMT). No. of bitstreams: 1 438275.pdf: 12783566 bytes, checksum: d6ff8fd347a19bd2c64de39963e3e8f0 (MD5) Previous issue date: 2012-03-27 / Background: Anticipation of epileptic seizures may allow acute interventions to reduce physical and psychosocial harm associated with unexpected attacks. Recent data suggest that electrical abnormalities evolve during many hours before a seizure and these may potentially be clinically identified as seizure prodromes. Objectives: We aimed to determine, in an objective and verifiable fashion, the types, prevalence, sensitivity, specificity and predictive value of seizure prodromes in patients with refractory partial epilepsies, as well to study the clinical and psychiatric correlates of these premonitory symptoms. Methods: We studied 55 adult patients who had at least one focal seizure recorded during of video-EEG monitoring. Patients noted any symptoms they associated with impending seizures and that information was complemented daily by entering actual seizure occurrence according to video- EEG. Detailed clinical and psychiatric data were then correlated with the occurrence of prodromes. Results: Thirty-six patients (65%) reported prodromal symptoms, a median of 12 hours before seizures. Half were related to mood changes. Female sex, higher baseline seizure frequency and a history of more severe depressive disorders independently correlated with the occurrence of prodromes. Mean specificity and PPV slightly above 80% contrasted with sensitivity and NPV slightly below 60%. Conclusion: Seizure prodromes in the context of presurgical evaluation are common in adult patients with medically refractory seizures and should be discussed with patients as a means to anticipate seizures and thus minimize harm. Development of acute interventions to prevent seizures at the time of prodromes is an attractive possibility. / Introdu??o: A antecipa??o de crises epil?ticas pode permitir interven??es agudas para reduzir danos f?sicos e psicol?gicos associados ? ocorr?ncia de crises inesperadas. Dados recentes sugerem que anormalidades el?tricas desenvolvem-se durante muitas horas antes de uma crise, podendo ser clinicamente identificadas como pr?dromos de crises epil?pticas. Objetivos: Nosso estudo se prop?s a determinar, de forma objetiva e verific?vel, os tipos, a preval?ncia, a sensibilidade, a especificidade e o valor preditivo dos pr?dromos em pacientes com epilepsia parciais refrat?rias, assim como estudar os correlatos cl?nicos e psiqui?tricos destes sintomas premonit?rios. M?todos: Foram estudados 55 pacientes adultos, com pelo menos uma crise parcial gravada por monitora??o por v?deo-EEG. Os pacientes observaram diversos sintomas que foram associados ?s crises iminentes, e estas informa??es foram registradas diariamente e complementadas pelos dados do registro da ocorr?ncia real de crise epil?ptica, de acordo com o v?deo-EEG. Dados cl?nicos e psiqui?tricos detalhados foram correlacionados com as ocorr?ncias de pr?dromos. Resultados: Trinta e seis pacientes (65%) relataram sintomas de pr?dromos, ocorrendo em uma mediana de 12 horas antes das crises epil?pticas. Metade destes sintomas foram relacionados ? altera??o de humor. Sexo feminino, frequ?ncia de crises alta e hist?ria de transtorno depressivo grave, foram correlacionados, de modo independente, com a ocorr?ncia dos pr?dromos. A especificidade m?dia e o VPP ficaram um pouco acima de 80%, contrastando com a sensibilidade, e o VPN, um pouco abaixo de 60%. Conclus?o: Pr?dromos, em um contexto de avalia??o pr?-cir?rgica, s?o comuns em pacientes com crises refrat?rias ? medica??o, devendo os mesmos ser discutidos com os pacientes, como um meio de antecipar as crises epil?pticas e, assim, minimizar os danos ocasionados por estas. O desenvolvimento de interven??es agudas, para prevenir as crises no momento em que os pr?dromos ocorrem, torna-se uma possibilidade interessante.

Made available in DSpace on 2015-04-14T13:35:31Z (GMT). No. of bitstreams: 1 438287.pdf: 659033 bytes, checksum: 74536bb270173b92a486ff2c17575495 (MD5) Previous issue date: 2012-03-28 / IgG anti-dsDNA antibodies are associated to lupus nephritis. Recent data suggest that IgM isotype is nephroprotector. We evaluated the frequency of IgG anti-dsDNA in patients with Systemic lupus erythemathosus (SLE) and its relation between IgG/IgM proportion and clinical manifestations of the disease. This transversal study included 137 SLE patients according to traditional criteria (92.5% female, 79.5% Caucasian) and 58 SLE individual (93.1% female, 81% Caucasian) selected by positivity for IgG anti-dsDNA. IgG and IgM anti-dsDNA antibodies were detected by Chrithidiae luciliae indirect immunofluorescence with cut point 1/10 dilution. The presence of IgG anti-dsDNA was associated to the presence of hemolytic anemia, leukopenia/lymphopenia and Complement depletion (p<0.001). Of the 58 patients positive for IgG anti-dsDNA 15 were also positive for IgM anti-dsDNA. The group presenting both isotypes showed significant less frequency of active urinary sediment when compared to isolated IgG anti-dsDNA (6.7% versus 34.9%, p=0.046). IgG/IgM proportion distribution evidenced a trend of higher medians in the presence of arthritis and leukopenia/lymphopenia [4 (2-8) versus 1 (1-2), p=0.070 and 4 (3-8) versus 1 (1-4), p=0.066, respectively]. Summarizing, the frequency of IG anti-dsDNA was relevant in our casuistic. Positive subpopulation for both IgG/IgM isotypes anti-dsDNA was less willing to urinary sediment alterations than IgG anti-dsDNA isolated population. These data suggest a distinct biologic behavior for IgM anti-dsDNA. / Anticorpos IgG anti-dsDNA se associam ? ocorr?ncia de nefrite l?pica. Relatos recentes sugerem que o isotipo IgM anti-dsDNA seja nefroprotetor. Avaliamos frequ?ncia de IgG anti-dsDNA em pacientes com l?pus eritematoso sist?mico (LES), e averiguamos a rela??o entre propor??o IgG/IgM anti-dsDNA e manifesta??es cl?nicas da doen?a. O estudo, transversal, incluiu 137 pacientes com LES de acordo com os crit?rios tradicionais (92,5% mulheres, 79,5% ra?a branca) e uma popula??o de 58 casos de LES (93,1% mulheres, 81% ra?a branca) selecionados por positividade para IgG anti-dsDNA. Anticorpos IgG e IgM anti-dsDNA foram detectados por imunofluoresc?ncia indireta com Crithidia luciliae, com ponto de corte na dilui??o 1/10. A presen?a de IgG anti-dsDNA se associou ? presen?a de anemia hemol?tica, leucolinfopenia e deple??o de Complemento (p<0, 001). Dos 58 pacientes com teste positivo para IgG anti-dsDNA, 15 foram tamb?m positivos para o isotipo IgM. O grupo com ambos os isotipos teve frequ?ncia significativamente menor de sedimento urin?rio ativo quando comparado ao grupo com IgG anti-dsDNA isolado (6,7% versus 34,9%, p=0, 046). A distribui??o da propor??o IgG/IgM anti-dsDNA evidenciou tend?ncia de medianas mais elevadas na presen?a de artrite e leucolinfopenia [4 (2-8) versus 1 (1-2), p=0, 070 e 4 (3-8) versus 1 (1-4), p=0, 066, respectivamente]. Em suma, a frequ?ncia de IgG anti-dsDNA foi relevante em nossa casu?stica. A subpopula??o positiva para ambos IgG e IgM anti-dsDNA foi menos propensa a altera??es de sedimento urin?rio do que aquela com IgG anti-dsDNA isolado. Estes dados sugerem um comportamento biol?gico distinto para o isotipo IgM anti-dsDNA.

Made available in DSpace on 2015-04-14T13:35:32Z (GMT). No. of bitstreams: 1 438285.pdf: 5375731 bytes, checksum: 4cabd22bcc7565970e16fa7e9057a2bb (MD5) Previous issue date: 2012-03-28 / Introduction: Patients with Frontal Lobe Epilepsy (FLE), although they generally show a good performance in traditional memory tests, they are very forgetful in daily life, which affects their academic, professional and social life. Such forgetfulness is related to Prospective Memory (PM), which consists in recalling, at the appropriate time, an intention to be performed in the future. Objective: This study investigated PM in patients with frontal epilepsy, analyzing the interference of the lesion, laterality and location of the epileptogenic focus in PM performance, as well as its correlation with other memory and executive function tests. Methodology: We conducted a case-control study to evaluate the PM, being comprised of 27 adult patients with frontal lobe epilepsy, confirmed by EEG (electroencephalography), VEEG (video electroencephalography), or MRI (cerebral magnetic resonance imaging). Out of this group, 16 showed lesion on the frontal region and 11 did not show any lesion. A group of 16 adults with no epilepsy formed the control group. All subjects underwent a neuropsychological evaluation, consisting of manual dominance tests, IQ (intelligence quotient) estimated test, verbal memory tests, (immediate and delayed) visual test, PM test, attention, verbal fluency and other executive function tests. They also answered a questionnaire for memory selfevaluation and a scale to identify psychiatric comorbidities. PM was assessed by a test that simulates daily life tasks. Results: The case group (10.3?4.2) showed a significantly lower mean than the control group (15.7?2.1) in the PM test. When comparing the group with lesion to the group with no lesion, they were not significantly different in PM performance. Regarding the lateralization of the epileptogenic focus, the group with bilateral focus had a worse performance in the PM than the group with the focus on the right, though it did not differ significantly from the group with the focus on the left. Conclusion: Patients with frontal lobe epilepsy had a worse prospective memory performance than the control group. The presence or absence of injury did not affect PM performance. Patients with bilateral focus had the worst PM performance. Regarding focus laterality (right or left), there was no difference in PM. PM performance was connected to attention and delayed visual memory. / Introdu??o: Pacientes com Epilepsia do Lobo Frontal (ELF), embora geralmente demonstrem um bom desempenho nos testes tradicionais de mem?ria, apresentam muitos esquecimentos na vida di?ria, comprometendo sua vida acad?mica, profissional e social. Tais esquecimentos referem-se ? Mem?ria Prospectiva (MP), que consiste em recordar, no momento adequado uma inten??o a desempenhar no futuro. Objetivo: Este estudo buscou investigar a MP nos pacientes com epilepsia frontal, analisando a interfer?ncia da presen?a de les?o, da lateralidade e da localiza??o do foco epileptog?nico no desempenho da MP, assim como sua correla??o com outros testes de mem?ria e de fun??es executivas. Metodologia: Foi realizado um estudo de caso-controle para avalia??o da MP, sendo constitu?do de 27 pacientes adultos com epilepsia de lobo frontal, confirmada por EEG (eletroencefalografia), VEEG (v?deo-eletroencefalografia) ou RM (resson?ncia magn?tica cerebral). Desse grupo, 16 apresentavam les?o em regi?o frontal e 11 n?o apresentavam nenhuma les?o. Um grupo de 16 adultos sem epilepsia constituiu o grupo controle. Todos os sujeitos realizaram avalia??o neuropsicol?gica, constitu?da de testes de domin?ncia manual, teste estimado de QI (Coeficiente de Intelig?ncia), testes de mem?ria verbal, visual (imediata e tardia), teste de MP, aten??o, flu?ncia verbal e demais testes de fun??o executiva. Tamb?m responderam a um Question?rio de auto-avalia??o da mem?ria e uma escala para identificar comorbidades psiqui?tricas. A MP foi avaliada atrav?s de um teste que simula tarefas da vida di?ria. Resultados: O grupo de casos (10,3?4,2) apresentou m?dia significativamente menor que o grupo controle (15,7?2,1) no teste de MP. Ao comparar o grupo com les?o e sem les?o, estes n?o se mostraram significativamente diferentes quanto ao desempenho na MP. Em rela??o ? lateraliza??o do foco epileptog?nico, o grupo com foco bilateral obteve pior desempenho na MP que o grupo ? direita, embora n?o tenha diferido de forma significativa do grupo ? esquerda. Conclus?o: Os pacientes com epilepsia frontal tiveram pior desempenho da mem?ria prospectiva do que o grupo controle; a presen?a ou n?o de les?o n?o interferiu no desempenho da MP; os pacientes com foco bilateral tiveram pior desempenho da MP. Em rela??o ? lateralidade do foco (direita ou esquerda) n?o houve diferen?a na MP. O desempenho da MP correlacionou-se com a aten??o e com a mem?ria visual tardia.

Made available in DSpace on 2015-04-14T13:35:32Z (GMT). No. of bitstreams: 1 438286.pdf: 4118090 bytes, checksum: 3f84072ed045d46706a18668827636e2 (MD5) Previous issue date: 2008-11-24 / Introduction: Previous studies showed a possible association between the T102C polymorphism of the serotonin 2A receptor (5-HT2A) and urinary incontinence in the elderly. Since serotonin is involved in the modulation of bladder sphincter control, such association is biologically plausible. Since the pharmacological treatment of urinary incontinence (UI) includes the use of serotonin reuptake inhibitors, complementary studies of this polymorphism are of scientific and clinical importance. Objectives: The aims of this study in older women living in a senior living community were: (1) to describe and compare the allelic and genotypic frequencies of the 102C polymorphism of the serotonin 2A receptor (5-HT2A) in incontinent and continent individuals; (2) to describe and compare the urodynamic parameters in incontinents carrying different genotypes/alleles; (3) to describe and compare the frequency of the urodynamic types of urinary incontinence (stress, urge and mixed) in incontinent individuals carrying different genotypes/alleles; and (4) to describe and compare the impact of UI on the quality of life in incontinent individuals carrying different genotypes/alleles. Methodology: A case-control study was conducted including 68 incontinent older women (submitted to urodynamic evaluation) and 162 continent older women (self-reporting). The criteria for exclusion were: use of diuretics, diabetes, non-Caucasian individuals, and severe mobility and neurological disturbances. The polymorphism was analyzed by the PCR-RFLP technique. The Ethics Committee approved the study, and all participants signed an informed consent form. Results: Incontinent older women showed a significantly greater frequency of the TT genotype (TT= 34.8%, CC= 19.3%, TC= 45.9%) compared to continent older women (TT=17%, CC=23.3%, TC=59.7%) and the general sample of the population (TT=21.5%, CC=16.6%, TC=61.9%) (p=0.001). The genetic frequencies of the three samples were in Hardy-Weinberg equilibrium. Urodynamic analysis showed a significant association between the TT genotype and greater detrusor pressure at maximal cystometric capacity, lower maximal cystometric capacity and reduced bladder compliance. The TT genotype also showed a higher prevalence of urge UI (44%) than did the other genotypes (p=0.01). Analyses of indicators of quality of life and UI demonstrated a greater negative impact in carriers of the C allele (CC+TC). Conclusion: Together, the results suggest that the T102C polymorphism of the 5-HT2A receptor gene has a physiological effect on the lower urinary tract of humans. This hypothesis needs to be confirmed by complementary studies. The effect of an imbalance in the quantity of this receptor, which occurs in the TT genotype, could be associated with a greater chance or urge UI in older women. / Introdu??o: estudos pr?vios mostraram poss?vel associa??o entre o polimorfismo T102C do receptor 2A da serotonina (5-HT2A) e incontin?ncia urin?ria em idosos. Como a serotonina est? envolvida na modula??o do controle vesical-esfincteriano, tal associa??o ? biologicamente plaus?vel. Uma vez que a terap?utica farmacol?gica da incontin?ncia urin?ria (IU) inclui o uso de inibidores da recapta??o da serotonina, estudos complementares deste polimorfismo s?o de relev?ncia cl?nico-cient?fica. Objetivos: em mulheres idosas que vivem na comunidade: (1) descrever e comparar as freq??ncias al?licas e genot?picas do polimorfismo 102C do receptor 2A da serotonina (5-HT2A) em idosas incontinentes e continentes; (2) descrever e comparar os par?metros urodin?micos nas idosas incontinentes portadoras de diferentes gen?tipos/alelos; (3) descrever e comparar a freq??ncia dos tipos de incontin?ncia urin?ria urodin?mica (de esfor?o, de incontin?ncia de urg?ncia e mista) nas idosas incontinentes portadoras de diferentes gen?tipos/alelos; (4) descrever e comparar o impacto da IU na qualidade de vida nas idosas incontinentes portadoras de diferentes gen?tipos/alelos. Metodologia: um estudo caso-controle foi conduzido, sendo 68 mulheres idosas incontinentes (submetidas ? avalia??o urodin?mica) e 162 mulheres continentes (auto-relato). Os crit?rios de exclus?o foram: uso de diur?ticos, diabetes, indiv?duos de outras etnias que n?o a caucasiana, dist?rbios de mobilidade e neurol?gicos graves. O polimorfismo foi analisado por t?cnica de biologia molecular PCR-RFLP. O Comit? de ?tica aprovou a pesquisa e todos os participantes assinaram Termo de Consentimento Livre e Esclarecido. Resultados: idosas incontinentes apresentaram freq??ncia do gen?tipo TT significativamente maior (TT= 34,8%, CC= 19,3%, TC= 45,9%) do que nas mulheres continentes (TT=17%, CC=23,3%, TC=59,7%) e na amostra geral da popula??o (TT=21,5%, CC=16,6%, TC=61,9%) (p=0,001). As freq??ncias gen?ticas das tr?s amostras estavam em equil?brio de Hardy-Weinberg. An?lise urodin?mica mostrou associa??o significativa entre o gen?tipo TT e maior press?o detrusora na capacidade cistom?trica m?xima, menor capacidade cistom?trica m?xima e complac?ncia vesical reduzida. O gen?tipo TT tamb?m apresentou maior preval?ncia de IU de urg?ncia (44%) do que os demais gen?tipos (p=0,01). O conjunto destes resultados sugeriu que o gen?tipo TT est? associado a altera??es de fatores fisiol?gicos, predisponentes a incontin?ncia urin?ria. Entretanto, an?lises de indicadores da qualidade de vida e a IU mostraram maior impacto negativo em portadoras do alelo C (CC+TC). Esta condi??o pode estar associada ? sugest?o de predisposi??o de portadoras do alelo C a dist?rbios emocionais. Conclus?o: o conjunto dos resultados sugere que o polimorfismo T102C do gene do receptor 5-HT2A tenha um poss?vel efeito fisiol?gico no trato urin?rio inferior (TUI) de seres humanos. Esta hip?tese precisa ser confirmada por estudos complementares. O efeito do desbalan?o na quantidade deste receptor, que ocorre no gen?tipo TT estaria associado ? maior chance de IU de urg?ncia na mulher idosa.

Made available in DSpace on 2015-04-14T13:35:32Z (GMT). No. of bitstreams: 1 438475.pdf: 1199552 bytes, checksum: 11115a2a9f4a42a185a775b4a566fe5b (MD5) Previous issue date: 2012-03-02 / ADULT (acro-dermato-ungueal-tooth) is a human genetic syndrome that manifests clinically by skin and embryonic appendages anomalies. This syndrome pathogenesis was first identified in 2001, but nowadays it is related to more than one mutation in p63 gene. Although described almost 20 years ago (1993) in Germany, this syndrome still have few reports and this is the first brazilian family. We report here the clinical aspects of five members of a family which clinical features corresponded to phenotypic ADULT manifestations. The clinical aspects included athelia/hypotelia, photosensitivity, dystophic nails, tooth anomalies and lacrimal duct obstruction. The adermatoglyphia, manifestation found in all affected members of this family, was not described before. The histologic examination demonstrated flattening of dermal papillae and electron microsopy showed disrupted collagen fibers. The genetic sequencing of blood ssample found a mutation in p63 gene, already known as R298Q. / A ADULT (acro-dermato-ungueal-lacrimal-tooth) ? uma s?ndrome gen?tica humana que se manifesta clinicamente por altera??es cut?neas e do desenvolvimento dos ap?ndices embrion?rios. Sua etiologia foi identificada inicialmente em 2001, mas atualmente sabe-se que est? relacionada a mais de uma muta??o no gene p63. Apesar de descrita pela primeira vez h? quase duas d?cadas (1993) na Alemanha, a s?ndrome ainda ? pouco reportada e esta ? a primeira fam?lia brasileira descrita. Neste trabalho descrevemos os aspectos cl?nicos de cinco indiv?duos de uma mesma fam?lia, os quais apresentavam manifesta??es fenot?picas compat?veis com a s?ndrome ADULT. Os achados cl?nicos incluem atelia/hipotelia, fotossensibilidade, distrofia ungueal, anormalidades dent?rias e obstru??o do ducto lacrimal. A adermatoglifia, manifesta??o cl?nica demonstrada em todos os acometidos desta fam?lia, n?o fora descrita anteriormente nos portadores da s?ndrome. A avalia??o histol?gica por microscopia ?ptica evidenciou retifica??o das papilas d?rmicas e a an?lise por microscopia eletr?nica mostrou altera??o nas fibras col?genas da derme. O sequenciamento gen?tico atrav?s de amostras de sangue perif?rico identificou uma muta??o no gene p63, previamente conhecida como R298Q.

Made available in DSpace on 2015-04-14T13:35:32Z (GMT). No. of bitstreams: 1 438586.pdf: 851444 bytes, checksum: 4403bec36e79f61219a752dde80a37db (MD5) Previous issue date: 2012-03-28 / Introduction: Spasticity is an incapacitating condition resultant from central nervous system injury such as the cerebral vascular accident, commonly known as stroke (STK). It is usually associated with hypertony and with a reduction in skeletal muscle force production. This condition may generate imbalance between antagonistic muscles at the ankle joint, which can be evaluated by torque ratios (TR). Purpose: to compare the dorsiflexor/plantarflexor (DF/PF) torque ratios between a post-stroke hemiparetic spastic group (STK) and a healthy control group (CON) and to evaluate STK group functionality. Methods: an isokinetic dynamometer was used to obtain maximal PF and DF torques at an angular velocity of 60?/s of hemiparetic spastic subjetcs (59.7 ? 13.74 years of age) and twelve healthy subjects (59.0 ? 13.64 years of age). TR were obtained through the division between the maximal DF and maximal PF torques. The STK group had their functionality evaluated through the Berg Balance Scale (BBS), the Barthel Index (BI), and the Timed Up and Go test (TUG). A Mann Whitney U test was used for the within group (spastic x non-spastic limbs) and for the between group (spastic x control) comparisons of the scale results and TR, whereas an independent T-test was used for the between groups comparison of the anthropometric variables (p &#8804;0.05). Results: The within STK group comparison revealed higher TR in the spastic side compared to the non-spastic contralateral side (0,81?0,25 and 0,43?0,41 respectively; p=0.01). The inter-group comparison revealed that the TR of the spastic side of the STK group was higher compared to the dominant side of the CON group (0,81?0,25 and 0,30? 0,10 respectively; p&#8804;0.01). No differences were observed for the TR between the non-spastic side of the STK group and the dominant side of the CON group (0,43?0,41 and 0,30? 0,10 respectively; p=0.56). In addition, no changes in functionality were observed in the STK patients. Discussion: These results indicate that both limbs of the STK group show muscle imbalance, which might be explained by the smaller PF torque in both limbs, resulting on an elevated TR. The elevated TR found in the CON group is probably related to the fact that all subjects were sedentary. The STK group showed normal values for functionality, suggesting that the time post injury and the spasticity degree probably influence the results of these scales. Conclusion: Muscle imbalance is present in both lower limbs of post-STK patients, although the TR are more affected in the spastic side. / Introdu??o: a espasticidade ? uma condi??o incapacitante decorrente de les?es do sistema nervoso central como o acidente vascular cerebral (AVC), podendo estar associada com a hipertonia e diminui??o da for?a nos m?sculos. Tal condi??o pode gerar desequil?brios entre as musculaturas da articula??o do tornozelo, podendo estes serem avaliados pelas raz?es de torque. Objetivos: avaliar a funcionalidade e comparar as raz?es de torque (RT) dos flexores dorsais e plantares (FD/FP) entre indiv?duos com hemiparesia esp?stica decorrente de AVC isqu?mico e indiv?duos controle. M?todos: participaram do estudo 9 indiv?duos com hemiparesia esp?stica (59,7 ? 13,74 anos) e 12 indiv?duos controles (59,0 ? 13,64 anos). As escalas funcionais utilizadas foram: escala modificada de Ashworth, ?ndice de Barthel, escala de Berg e o teste Timed Up Go. Um dinam?metro isocin?tico foi utilizado para a obten??o do torque m?ximo em uma velocidade angular de 60?/s. Para a obten??o das raz?es, o torque m?ximo dos FD foi dividido pelo torque m?ximo dos FP. Foi utilizado o Teste U de Mann Withney para compara??o intra e entre grupos e Teste T independente para compara??o das medidas antropom?tricas entre os grupos (p &#8804;0,05). Resultados: na compara??o intra-indiv?duos, houve uma diferen?a significativa entre as m?dias das RT no grupo AVC (lado afetado 0,81?0,25 e n?o afetado 0,43?0,41) (p=0,01). Para a compara??o inter-grupos, o lado afetado 0,81?0,25 do grupo AVC foi significativamente diferente do lado dominante 0,30?0,10 dos indiv?duos controle (p&#8804;0,01). N?o houve diferen?a significativa entre o lado n?o afetado do grupo AVC 0,43?0,41 e o lado dominante do grupo controle 0,30? 0,10 (P=0,56). N?o houve altera??es da funcionalidade dos indiv?duos do grupo AVC. Discuss?o: estes resultados indicam que tanto a perna acometida como a contralateral do grupo AVC apresentam desequil?brios musculares podendo ser explicado pelo menor torque produzido pelos FP, ocasionando uma RT aumentada. O grupo controle tamb?m apresentou RT alterada, possivelmente por serem sedent?rios. Quanto ? funcionalidade, o grupo AVC apresentou resultados de normalidade, sugerindo que o tempo de les?o e o grau de espasticidade podem influenciar nestas vari?veis. Conclus?o: os desequil?brios musculares est?o presentes em ambos os membros inferiores no grupo AVC, por?m as RT s?o mais alteradas no hemicorpo esp?stico.

Made available in DSpace on 2015-04-14T13:35:33Z (GMT). No. of bitstreams: 1 438529.pdf: 18860537 bytes, checksum: 9c31f74e1e908515a22fbc3a7838b2b1 (MD5) Previous issue date: 2012-05-29 / Gastrointestinal sarcomatoid tumors (GIST) are rare malignancies, corresponding to 1 - 3% of alli GI cancers. Nevertheless, GISts are the most common GI mesenchimal malignancies. GISTs are heterogeneous in presentation, clinical course and response to therapy. Their prognosis can be roughly estimated at diagnosis by assessing tumor size, mitotic index and the topography of the primary lesion. Despite the proved utility of these prognostic factors, their limitations are well documented, and a more refined set of biological markers are much needed. The abnormal activation of the cell survival signaling pathway provided by PI3K/Akt/PTEN proteins is a well known feature in advanced epithelial and hematological malignancies, impacting the aggressiveness of the disease as well as the resistance to different traditional therapies or biological agents. Besides their multi-effect in cell survival mechanisms, the PI3K/Akt/PTEN pathway is a powerful activator of angiogenesis via VEGF protein family transcription. The different isoforms of VEGF will in turn activate the VEGF receptor (VEGFR) at the surface of endothelial cells. Therefore, VEGFR is a reliable marker of angiogenesis in human tumors. We sought to evaluate the expression of VEGFR and Akt proteins in a series of GIST patients at diagnosis, treated in a single institution, in order to correlated the levei of expression of these proteins to clinical outcomes, such as overall survival (OS) and disease free survival (DFS). The levei of expression of these proteins was also correlated to the same outcomes in a subgroup of patients with advanced disease who received more than three months of therapy with Imatinib Mesylate (GleeveC?). Methods - 48 GIST patients were evaluated. Immunohystochemistry for VEGFR and Akt was performed by tissue microarray. Results - Akt hyperexpression was statistically correlated with a shorter DFS in the group of patients with metastatic disease (ali of them receiving GleeveC?). This correlation was not observed in early cases (defined as curable disease - stages I to III). We have not observed correlation between Akt expression and OS in any clinical stage. Lower VEGFR expression was associated to a significant better OS in ali stages (including patients receiving GleeveC?). Conversely, DFS was not affected by the levei of expression of VEGFR. CONCLUSIONS - Low VEGFR expression was related to a better prognosis in any clinicalstage of GIST, reflected in larger OS. The fact that this effect was observed in GleeveC? treated patients suggests that the betler response to the drug is much more related to the biology of the tumor than to the treatment itself. Akt showed also a promising role as a prognostic marker for disease free survival in advanced disease, indicating that GISTs with hyperexpressed Akt pathway behave more aggressively or may be less sensitive to GleeveC?. / Introdu??o: GISTs s?o raros, correspondendo de 1 a 3% de todas as neoplasias do trato gastrointestinal, entretanto, s?o as neoplasias mesenquimais mais comuns desta localiza??o. Possuem uma apresenta??o, comportamento cl?nico e resposta ? terapia heterog?neos. O progn?stico pode ser grosseiramente estimado pelo tamanho tumoral ao diagn?stico, topografia e ?ndice mit?tico. Apesar da utilidade destes fatores de progn?stico de simples obten??o, a heterogeneidade da doen?a exige que marcadores mais espec?ficos sejam aplicados para uma avalia??o individual n?o apenas progn?stica ao diagn?stico, mas tamb?m preditiva ao tratamento com novas drogas dispon?veis. A ativa??o aberrante das prote?nas da via de sinaliza??o PI3K/Akt/PTEN ? um fen?meno relativamente comum em neoplasias epiteliais e hematol?gicas, com repercuss?o tanto na agressividade da neoplasia como na sua resist?ncia adquirida a tratamentos anti-neopl?sicos. Al?m da sinaliza??o para mecanismos de sobreviv?ncia, a via PI3K/Akt/PTEN est? envolvida na ativa??o de angiog?nese por meio da transcri??o de VEGF e secundariamente do seu receptor endotelial, VEGFR. O objetivo deste trabalho foi avaliar a express?o das prote?nas VEGFR, Akt e PTEN em pacientes com GIST ao diagn?stico, na tentativa de correlacionar a mesma com desfechos cl?nicos. Paralelamente acompanhamos o efeito do n?vel de express?o destas prote?nas em um subgrupo de pacientes com doen?a avan?ada que recebeu a medica??o Mesilato de Imatinib (GliveC?). M?todo: Avalia??o imunoistoqu?mica com m?todo TMA de 48 esp?cimes de GISTs utilizando os anticorpos monoclonais para Akt e VEGFR. A hiperexpress?o de Akt foi verificada em 33,3% e VEGFR em 75% das amostras. Na an?lise do grupo geral de pacientes, a hiper-express?o de Akt correlacionou-se com uma SLP (sobrevida livre de progress?o) estatisticamente encurtada (p>O.05) exclusivamente para casos com doen?a metast?tica. Esta correla??o n?o foi observada em casos com doen?a n?o inicial (est?gios I a III). No entanto, mesmo em doen?a avan?ada, a hiper-express?o de Akt n?o teve impacto na sobrevida global. Como o grupo de pacientes com doen?a avan?ada foi o grupo que recebeu GliveC?, a correla??o com SLP e hiper-express?o de Akt se manteve. A aus?ncia de express?o de VEGFR se associou com melhor sobrevida global (SG) em todos os est?gios (incluindo os pacientes que receberam GliveC?), mas n?o com sobrevida livre de doen?a (SLD). Este dado sugere que os pacientes com baixa express?o de VEGFR poderiam ter uma doen?a de biologia mais indolente, mesmo que a taxa de recorr?ncia seja id?ntica ao grupo com VEGFR hiper-expresso. Conclus?es: os resultados deste estudo sugerem que a baixa express?o de VEGFR ? um fator de progn?stico favor?vel em pacientes com doen?a em qualquer est?gio. A hiperexpress?o de Akt associa-se a uma menor SLP apenas em casos avan?ados, sugerindo que a ativa??o desta via poderia ser um mecanismo adquirido em etapas finais da doen?a que conferem resist?ncia ao GliveC?.

Made available in DSpace on 2015-04-14T13:35:33Z (GMT). No. of bitstreams: 1 439097.pdf: 7980733 bytes, checksum: af8f6a7fa6a599651957ad5f12054783 (MD5) Previous issue date: 2012-05-16 / Tuberculosis continues to be one of the deadliest diseases in the world. The emergence of drug-resistant strains of Mycobacterium tuberculosis, the unbearable side effects of the available drugs and the frequent patient non-compliance in completing the therapy have increased the need for development of new effective agents. We have previously demonstrated a potent in vitro inhibitory activity for two pentacyano(isoniazid)ferrate(II) compounds, namely IQG-607 and IQG-639 against the M. tuberculosis enoyl-ACP reductase enzyme. Importantly, IQG-607 and IQG-639 were active against cultures of M. tuberculosis H37Rv and two isoniazid-resistant clinical isolates in vitro. In the present study, the activity of these compounds was evaluated by using an in vivo murine model of tuberculosis. Swiss mice were infected with M. tuberculosis H37Rv strain, and IQG-607 and IQG-639 (250 mg/kg) were administered during 28 or 56 days. As well, a dose-response study was performed with IQG-607 (at 5, 10, 25, 50, 100, 200 and 250 mg/kg). The activity of test compounds was compared with that of the positive control drug isoniazid at 25 mg/kg. After 28 or 56 days of treatment, either IQG-607 or isoniazid significantly reduced M. tuberculosis-induced splenomegaly, and also significantly diminished the colony-forming units in both spleens and lungs. IQG-607 or isoniazid ameliorated the lung macroscopic aspect, reducing the lung lesions to a similar extent. However, IQG-639 was not capable of significantly modifying any evaluated parameter. IQG-607 did not display a classical dose-dependent profile in our murine model of tuberculosis, and 10 mg/kg was the lowest dose able to show significant activity, which was similar to the inhibition observed for higher doses. In addition, experiments using early and late controls of infection revealed a bactericidal activity for IQG-607 in our model. The promising activity of IQG-607 in M. tuberculosis-infected mice suggests that this compound might represent a good candidate for clinical development as a new antimycobacterial agent. / A tuberculose ? uma das principais causas de morte no mundo. O surgimento e dissemina??o de cepas de Mycobacterium tuberculosis resistentes a f?rmacos, os efeitos indesej?veis dos f?rmacos atualmente dispon?veis e a falta de ades?o dos pacientes ao tratamento t?m aumentado a necessidade do desenvolvimento de novos agentes anti-tuberculose. Estudos pr?vios revelaram uma potente atividade inibit?ria in vitro de dois compostos pentaciano(isoniazida)ferrato(II), denominados IQG-607 e IQG- 639, frente a enzima enoil-ACP redutase de M. tuberculosis. Ainda, o IQG- 607 e o IQG-639 foram ativos quando testados em culturas de M. tuberculosis H37Rv e sobre dois isolados cl?nicos resistentes ? isoniazida in vitro. Neste trabalho, a atividade destes dois compostos foi avaliada in vivo, utilizando um modelo murino de infec??o por M. tuberculosis. Camundongos su??os foram infectados com a cepa de M. tuberculosis H37Rv e o IQG-607 ou o IQG-639 (250 mg/kg) foram administrados aos animais durante 28 ou 56 dias. Adicionalmente, um estudo de dose-resposta foi realizado com o composto IQG-607, empregando as doses de 5, 10, 25, 50, 100, 200 e 250 mg/kg. As atividades dos compostos-teste foram comparadas ? atividade da isoniazida (25 mg/kg), o controle positivo do tratamento. Ap?s 28 ou 56 dias de tratamento, tanto o IQG-607 quanto a isoniazida reduziram significativamente a esplenomegalia induzida pela infec??o e, tamb?m, diminu?ram as unidades formadoras de col?nia, tanto nos pulm?es quanto nos ba?os dos animais tratados. O IQG-607 e a isoniazida melhoraram o aspecto macrosc?pico dos pulm?es, reduzindo as les?es pulmonares de maneira semelhante. Por sua vez, o IQG-639 n?o foi capaz de modificar significativamente nenhum par?metro avaliado neste estudo. O IQG-607 n?o apresentou um perfil cl?ssico de dose depend?ncia, sendo observada atividade inibit?ria significativa similar, entre as doses de 10 mg/kg e 250 mg/kg. Al?m disto, um experimento utilizando um controle pr?-tratamento demonstrou que o IQG-607 possui atividade bactericida no nosso modelo. A atividade satisfat?ria do IQG-607 em camundongos infectados com M. tuberculosis sugere que este composto pode ser um candidato promissor no desenvolvimento cl?nico de um novo agente antimicobacteriano.