Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-02-05T23:00:04Z No. of bitstreams: 1 LiviaDeLourdesDeSousaPinto_DISSERT.pdf: 1563914 bytes, checksum: afff2cde0e6703ffa7b4fae03c2036ac (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-02-16T22:03:58Z (GMT) No. of bitstreams: 1 LiviaDeLourdesDeSousaPinto_DISSERT.pdf: 1563914 bytes, checksum: afff2cde0e6703ffa7b4fae03c2036ac (MD5) / Made available in DSpace on 2016-02-16T22:03:58Z (GMT). No. of bitstreams: 1 LiviaDeLourdesDeSousaPinto_DISSERT.pdf: 1563914 bytes, checksum: afff2cde0e6703ffa7b4fae03c2036ac (MD5) Previous issue date: 2015-03-13 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Condroitim sulfato (CS) ? um glicosaminoglicano natural presente na matriz extracelular de tecidos conectivos, podendo ser extra?do e purificado desses tecidos. O CS est? envolvido em diversas fun??es biol?gicas, o que pode estar relacionado ? variabilidade estrutural que possui, apesar da simplicidade da cadeia linear dessa mol?cula. Pesquisas na ?rea biotecnol?gica e farmacol?gica com rejeitos provenientes da aquicultura vem sendo desenvolvidas no Brasil. Nas ?ltimas d?cadas, a til?pia (Oreochromis niloticus), peixe nativo da ?frica, tem sido uma das esp?cies mais cultivadas em v?rias regi?es do mundo, inclusive no Brasil. A tilapicultura ? uma atividade economica cujo principal inconveniente ? a grande quantidade de res?duos que s?o descartados pelos produtores. Entende-se que o material descartado pode ser aproveitado em pesquisas como fonte de mol?culas com importante aplica??o biotecnol?gica, o que tamb?m contribui na redu??o de impactos ambientais e favorece o desenvolvimento dessa atividade de maneira ecologicamente correta. Dessa forma, v?sceras de til?pias nil?tica foram submetidas ? prote?lise, em seguida os glicosaminoglicanos foram complexados com resina de troca i?nica (Lewatit), fracionados com volumes crescentes de acetona e purificados atrav?s da cromatografia de troca i?nica DEAE-Sephacel. Na sequ?ncia, a fra??o foi analisada atrav?s de eletroforese em gel de agarose e resson?ncia magn?tica nuclear (RMN). O perfil eletrofor?tico do composto, a an?lise dos espectros 1H de RMN e a correla??o do HSQC permitem afirmar que o composto corresponde a uma mol?cula de condroitim sulfato. O ensaio de MTT foi utilizado para avalia??o da viabilidade celular na presen?a do CS isolado de til?pia e mostrou que o composto n?o ? citot?xico a c?lulas normais provenientes do fibroblasto de embri?o de camundongos (3T3). Ent?o, o composto foi testado quanto a capacidade de reduzir o influxo de leuc?citos em modelo de peritonite aguda (in vivo) induzida por tioglicolato de s?dio. Nesse contexto, foi realizada a contagem total e diferencial de leuc?citos do sangue e l?quido peritoneal coletadas, respectivamente, da veia cava e do lavado peritoneal de cada animal submetido ao experimento. O condroitim sulfato, pela primeira vez isolado de til?pia (CST ), foi capaz de reduzir a migra??o de leuc?citos ? cavidade peritoneal de camundongos inflamados em at? 80,4% na dose de 10?g/kg. Os resultados mostram ainda que houve redu??o significativa (p<0,001) da popula??o de polimorfonucleares do lavado peritoneal nas tr?s doses testadas (0,1?g/kg; 1?g/kg e 10?g/kg) quando comparado ao controle positivo (apenas tioglicolato). Portanto, uma vez que a estrutura e o mecanismo de a??o do CST tenham sido totalmente elucidados, esse composto pode apresentar potencial para uso terap?utico em doen?as inflamat?rias. / Chondroitin sulfate (CS) is a naturally glycosaminoglycan found in the extracellular matrix of connective tissues and it may be extracted and purified those tissues. CS is involved in various biological functions, which may be related to the having structural variability, despite the simplicity of the linear chain structure from this molecule. Researches in biotechnology and pharmaceutical field with wastes from aquaculture has been developed in Brazil. In recent decades, tilapia (Oreochromis niloticus), native fish from Africa, has been one of the most cultivated species in various regions of the world, including Brazil. The tilapia farming is a cost-effective activity, however, it generates large amount of wastes that are discarded by producers. It is understood that waste from tilapia can be used in research as a source of molecules with important biotechnological applications, which also helps in reducing environmental impacts and promote the development of an ecofriendly activity. Thus, nile tilapia viscera were subjected to proteolysis, then the glycosaminoglycans were complexed with ion exchange resin (Lewatit), it was fractionated with increasing volumes of acetone and purified by ion exchange chromatography DEAE-Sephacel. Further, the fraction was analyzed by agarose gel electrophoresis and nuclear magnetic resonance (NMR). The electrophoretic profile of the compound together the analysis of 1H NMR spectra and the HSQC correlation allow to affirm that the compound corresponds to a molecule like chondroitin sulfate. MTT assay was used to assess cell viability in the presence of CS tilapia isolated and showed that the compound is not cytotoxic to normal cells such as cells from the mouse embryo fibroblast (3T3). Then, this compound was tested for the ability to reduce the influx of leukocytes in model of acute peritonitis (in vivo) induced by sodium thioglycolate. In this context, it was done total and differential leukocytes counting in the blood and peritoneal fluid collected respectively from vena cava and the peritoneal cavity of the animals subjected to the experiment. The chondroitin sulfate for the first time isolated from tilapia (CST ) was able to reduce the migration of leukocytes to the peritoneal cavity of inflamed mice until 80.4 per cent at a dose 10?g/kg. The results also show that there was a significant reduction (p<0.001) of the population of polymorphonuclear leukocytes from peritoneal cavity in the three tested doses (0.1?g/kg; 1?g/kg and 10?g/kg) when it was compared to the positive control (just thioglycolate). Therefore, since the CST structure and mechanism of action has been completely elucidated, this compound may have potential for therapeutic use in inflammatory diseases

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-03-22T19:40:44Z No. of bitstreams: 1 MarianaAngelicaOliveiraBitencourt_TESE.pdf: 3370621 bytes, checksum: 9ed06db62a38c6ae8f8b6f074ccf7b06 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-03-28T20:16:41Z (GMT) No. of bitstreams: 1 MarianaAngelicaOliveiraBitencourt_TESE.pdf: 3370621 bytes, checksum: 9ed06db62a38c6ae8f8b6f074ccf7b06 (MD5) / Made available in DSpace on 2016-03-28T20:16:41Z (GMT). No. of bitstreams: 1 MarianaAngelicaOliveiraBitencourt_TESE.pdf: 3370621 bytes, checksum: 9ed06db62a38c6ae8f8b6f074ccf7b06 (MD5) Previous issue date: 2015-03-20 / Os acidentes ocasionados por animais pe?onhentos, pela frequ?ncia com que ocorrem e pela mortalidade que ocasionam, representam um s?rio problema de sa?de p?blica em diversas regi?es do Brasil, bem como em outros pa?ses do mundo. O uso de extratos de plantas medicinais como ant?doto para casos de envenenamento ? uma antiga pr?tica utilizada, ainda hoje, em muitas comunidades que n?o t?m acesso ? soroterapia. As plantas medicinais representam uma importante fonte de obten??o de compostos bioativos capazes de auxiliar diretamente no tratamento do envenenamento ou indiretamente, suplementando a soroterapia utilizada atualmente. O objetivo deste trabalho ? avaliar o efeito dos extratos aquosos, fra??es e compostos isolados das esp?cies Mimosa. Tenuiflora (jurema preta) e Harconia speciosa (mangaba) no processo inflamat?rio induzido por carragenina e as pe?onhas de Bothrops jararaca e Tityus. serrulatus. Os resultados demonstraram que tanto os extratos de M. tenuiflora quanto de H. speciosa foram capazes de inibir a migra??o celular e a produ??o de citocinas no modelo de peritonite induzido por carragenina e pe?onha de T. serrulatus. No modelo de envenenamento por B. jararaca, os camundongos tratados com os extratos das plantas em estudo reduziram o influxo leucocit?rio para a cavidade peritoneal. Por ?ltimo, os extratos das plantas M. tenuiflora e H. speciosa apresentaram atividade antiflog?stica, reduzindo a forma??o do edema exercendo tamb?m uma a??o inibit?ria da migra??o de leuc?citos e dano tecidual na inflama??o local induzida pela pe?onha de B. jararaca. Al?m disso, foi desenvolvida a an?lise fitoqu?mica de ambos os extratos aquosos obtidos. Nessa abordagem,foi poss?vel identificar, por meio de Cromatografia em Camada Delgada (CCD), a presen?a de flavon?ides e saponinas ou terpenos no extrato aquoso da esp?cie vegetal M. tenuiflora. Paralelamente, por meio da an?lise por Cromatografia L?quida de Alta Efici?ncia (CLAE), foi poss?vel identificar a presen?a de rutina e ?cido clorog?nico no extrato aquoso da planta H. speciosa. A partir dos resultados apresentados, pode-se concluir ent?o, que a administra??o dos extratos, fra??es e compostos isolados de M. tenuiflora e H. speciosa resultou na inibi??o do processo inflamat?rio em diversos modelos experimentais. Este estudo demonstra, pela primeira vez, o efeito das plantas M. tenuiflora e H. speciosa na inibi??o da inflama??o causada pelas pe?onhas de B. jararaca e T. serrulatus. / Accidents caused by venomous animals represents a significant and serious public health problem in certain regions of Brazil, as well as in other parts of the world by the frequency with which they occur and the mortality they cause. The use of plant extracts as an antidote for poisoning cases is an ancient practice used in many communities that have no access to antivenom. Medicinal plants represent an important source of obtaining bioactive compounds able to assist directly in the treatment of poisoning or indirectly supplementing serum therapy currently used. The aim of this study was to evaluate the effect of extracts, fractions and isolated compounds from M. tenuiflora and H. speciosa in the inflammatory process induced by carrageenan and the venom of B. jararaca and T. serrulatus. The results showed that both M. tenuiflora and H. speciosa were capable of inhibiting cell migration and cytokines levels in peritonitis induced by carrageenin and venom of T. serrulatus. In poisoning by B. jararaca model, mice treated with the plants in studies decreased the leukocyte influx into the peritoneal cavity. Finally the M. tenuiflora and H. speciosa had antiphlogistic activity, reducing edema formation and exerted inhibitory action of leukocyte migration in local inflammation induced by the venom of B. jararaca. Through of Thin Layer Chromatography (TLC) analysis was possible identified the presence of flavonoids ,saponins and/or terpenes in aqueous extract of M. tenuiflora. By High Performance Liquid Chromatography analysis, it was possible to identify the presence of rutin and chlorogenic acid in aqueous extract of H. speciosa. We conclude that the administration of extracts, fractions and isolated compounds of H. speciosa and M. tenuiflora resulted in inhibition of the inflammatory process in different experimental models. This study demonstrates for the first time the effect of M. tenuiflora and H. speciosa in inhibition of the inflammation caused by B. jararaca and T. serrulatus venom.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-04-25T22:57:37Z No. of bitstreams: 1 AnaCellySouzaDosSantos_DISSERT.pdf: 1317537 bytes, checksum: b64edb8897e90d29039563de6db801af (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-04-27T21:45:33Z (GMT) No. of bitstreams: 1 AnaCellySouzaDosSantos_DISSERT.pdf: 1317537 bytes, checksum: b64edb8897e90d29039563de6db801af (MD5) / Made available in DSpace on 2016-04-27T21:45:33Z (GMT). No. of bitstreams: 1 AnaCellySouzaDosSantos_DISSERT.pdf: 1317537 bytes, checksum: b64edb8897e90d29039563de6db801af (MD5) Previous issue date: 2015-03-27 / A s?ndrome dos ov?rios polic?sticos (SOP) ? considerada a endocrinopatia mais comum na fase reprodutiva da mulher, com preval?ncia que varia entre 15 a 20%. Al?m das altera??es hormonais e reprodutivas, ? comum na SOP a presen?a de fatores de risco para desenvolvimento de doen?as cardiovasculares (DCV) como diabetes mellitus, resist?ncia ? insulina (RI), obesidade visceral, inflama??o cr?nica de baixo grau e dislipidemia. Devido ? elevada frequ?ncia da obesidade associada ? SOP, a perda de peso ? considerada como o tratamento de primeira linha para a s?ndrome por melhorar as altera??es metab?licas e normalizar os andr?genos s?ricos, restaurando a fun??o reprodutiva destas pacientes. Objetivos: avaliar os marcadores inflamat?rios e a RI em mulheres com SOP e ovulat?rias saud?veis com diferentes estados nutricionais e como os par?metros inflamat?rios e hormonais se apresentam ap?s a perda de peso, atrav?s da restri??o cal?rica nas portadoras da s?ndrome. M?todos: O fator de necrose tumoralalfa (TNF-?), a interleucina-6 (IL-6) e a prote?na c-reativa (PCR) foram avaliados em amostras de soro de 40 mulheres em idade reprodutiva. Na primeira fase do estudo, as volunt?rias foram divididas em quatro grupos: Grupo I (n?o eutr?ficas com SOP, n=12); Grupo II (n?o eutr?ficas sem SOP, n=10), Grupo III (eutr?ficas com SOP, n=08) e Grupo IV (eutr?ficas sem SOP, n=10). A categoriza??o dos grupos foi realizada pelo ?ndice de massa corporal (IMC), de acordo com a organiza??o mundial de sa?de (OMS) em n?o eutr?fica, mulheres com IMC ? 25 (kg/m?) e eutr?ficas, IMC entre 18,9-24,9 (kg/m?). A RI foi determinada atrav?s do ?ndice HOMA-IR. Na segunda fase do estudo foi realizada uma interven??o nutricional controlada e os par?metros inflamat?rios foram avaliados em 21 mulheres sobrepeso e obesas com SOP, antes e depois da perda de peso. Todas as pacientes receberam uma dieta hipocal?rica com redu??o de 500 kcal/dia do consumo habitual com concentra??es padr?o de macronutrientes. Resultados: Fase 1: pacientes com SOP apresentaram n?veis aumentados da PCR (p<0,01) e HOMA-IR (p<0,01). Quando divididas por IMC, tanto o grupo n?o eutr?fico com SOP (I) quanto eutr?fico com SOP(III) apresentou n?veis aumentados de PCR (I=2,35?0,55mg/L e III= 2,63?0,65mg/L; p<0,01) e HOMA-IR (I= 2,16?2,54 e III= 1,07?0,55; p<0,01). N?o foram encontradas diferen?as de TNF-? e IL-6 entre os grupos. Fase 2: Ap?s a perda de peso de 5% do peso inicial ocorreu uma redu??o em todos os n?veis s?ricos dos componentes do perfil inflamat?rio avaliados, PCR (154.75 ? 19.33) vs (78.06 ? 9.08), TNF- ? (10.89 ? 5.09) vs (6.39 ? 1.41) e IL6 (154.75 ? 19.33) vs (78.06 ? 9.08) (p < 0.00) em associa??o com a melhora de alguns par?metros hormonais avaliados. Conclus?o: A SOP contribuiu para o surgimento da inflama??o cr?nica e das altera??es no metabolismo da glicose atrav?s do aumento da PCR, da insulina e do HOMA-IR, independente do estado nutricional e a perda de peso melhoraram o estado inflamat?rio e o perfil hormonal das pacientes avaliadas. / The polycystic ovary syndrome (PCOS) is considered the most common endocrine disorder in reproductive age women, with a prevalence ranging from 15 to 20%. In addition to hormonal and reproductive changes, it is common in PCOS the presence of risk factors for developing cardiovascular disease (CVD) and diabetes mellitus, insulin resistance (IR), visceral obesity, chronic low-grade inflammation and dyslipidemia. Due to the high frequency of obesity associated with PCOS, weight loss is considered as the first-line treatment for the syndrome by improving metabolic and normalizes serum androgens, restoring reproductive function of these patients. Objectives: To evaluate the inflammatory markers and IR in women with PCOS and healthy ovulatory with different nutritional status and how these parameters are displayed after weight loss through caloric restriction in with Down syndrome. Methods: Tumor necrosis factor-alpha (TNF-?), interleukin-6 (IL-6) and C-reactive protein (CRP) were assessed in serum samples from 40 women of childbearing age. The volunteers were divided into four groups: Group I (not eutrophic with PCOS, n = 12); Group II (not eutrophic without PCOS, n = 10), Group III (eutrophic with PCOS, n = 08) and Group IV (eutrophic without PCOS, n = 10). The categorization of groups was performed by body mass index (BMI), according to the World Health Organization (WHO) does not eutrophic, overweight and obesity (BMI> 25 kg / m?) and normal weight (BMI <24.9 kg / m?). IR was determined by HOMA-IR index. In the second phase of the study a controlled dietary intervention was performed and inflammatory parameters were evaluated in 21 overweight and obese women with PCOS, before and after weight loss. All patients received a low-calorie diet with reduction of 500 kcal / day of regular consumption with standard concentrations of macronutrients. Results: Phase 1: PCOS patients showed increased levels of CRP (p <0.01) and HOMAIR (p <0.01). When divided by BMI, both not eutrophic group with PCOS (I) as eutrophic with PCOS (III) showed increased levels of CRP (I = 2.35 ? 0,55mg / L and 2.63 ? III = 0,65mg / L; p <0.01) and HOMA-IR (I = 2.16 ? 2.54 and III = 1.07 ? 0.55; p <0.01). There were no differences in TNF-? and IL-6 between groups. Step 2: After the weight loss of 5% of the initial weight was reduced in all of the components of serum assessed inflammatory profile, PCR (154.75 ? 19:33) vs (78.06 ? 8.9) TNF ? (10.89 ? 5.09) vs (6:39 ? 1:41) and IL6 (154.75 ? 19:33) vs (78.06 ? 08.09) (p <0:00) in association with improvement some hormonal parameters evaluated. Conclusion: PCOS contributed to the development of chronic inflammation and changes in glucose metabolism by increasing CRP, insulin and HOMA-IR, independent of nutritional status. The weight loss, caloric restriction has improved the inflammatory condition and hormonal status of the evaluated patients.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-07-25T23:07:30Z No. of bitstreams: 1 PatriciaIngridMacedoDeCastro_DISSERT.pdf: 960843 bytes, checksum: 3369f0056a2e2ab1f071631a2015066a (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-08-04T20:48:06Z (GMT) No. of bitstreams: 1 PatriciaIngridMacedoDeCastro_DISSERT.pdf: 960843 bytes, checksum: 3369f0056a2e2ab1f071631a2015066a (MD5) / Made available in DSpace on 2016-08-04T20:48:06Z (GMT). No. of bitstreams: 1 PatriciaIngridMacedoDeCastro_DISSERT.pdf: 960843 bytes, checksum: 3369f0056a2e2ab1f071631a2015066a (MD5) Previous issue date: 2015-11-30 / A pr?-ecl?mpsia ? uma doen?a que afeta 3-8% das mulheres gr?vidas. Os fatores de risco para essa doen?a n?o s?o completamente compreendidos, mas incluem desregula??o da resposta imune oriundos de defeitos na placenta??o, fatores ambientais e gen?ticos. O presente estudo teve como objetivo investigar associa??o varia??o na quantidade de receptores de citocinas pr?-inflamat?rias (IL-1R, IL-6R e TNF-?R) estariam envolvidos com a pr?-ecl?mpsia. Receptores de citocinas (IL-1R2, TNF-?R1 e IL-6R) foram avaliados em c?lulas mononucleares das gr?vidas normotensas (controle n=11) e gr?vidas com pr?-ecl?mpsia (PE, n=24). Mulheres com pr?-eclampsia tinham peso mais elevado no in?cio da gravidez (p=0.0171). Foi observado uma diminui??o de mon?citos cl?ssicos, mas n?o de mon?citos intermedi?rios e n?o-cl?ssicos na pr?-ecl?mpsia. A frequ?ncia dos receptores de citocinas proinflamat?rias IL-1R2, TNF-?R IL-6R aderidos a membrana das subpopula??es de mon?citos (cl?ssicos, intermedi?rios e n?o cl?ssicos) e linf?citos (CD3+CD4+ e CD3+CD8+) estavam diminu?das em pacientes com pr?-ecl?mpsia, quando comparados com gr?vidas normais. A redu??o na quantidade de receptores de citocinas IL-1R2, TNF-?R1 e IL-6R em mon?ciots e linf?citos pode ser um fator mantenedor do estado inflamat?rio na pr?-eclampsia. / Preeclampsia is a disease specific of human pregnancy that affects 3-8% of pregnant women, and it is one of the three leading causes of maternal mortality and morbidity. The disease is characterized by hypertension and proteinuria after the 20th week of gestation. The risk factors for this disease are not completely understood but appear to include dysregulation of the immune response arising from defects in placentation, environmental and genetic factors. This study aimed to determine whether the variation in the amount of proinflammatory cytokine receptors IL-1R2, IL-6R and TNF-?R1 would be involved in preeclampsia. They were recruited women with preeclampsia (n=24) and women who evolved during pregnancy without changes in blood pressure (n=12) were recruited. Clinical and laboratory data were collected. The cytokine receptors (IL-1R2, TNF-?R1 and IL-6R) were assessed in mononuclear cells isolated from peripheral blood using flow cytometry (Control = 8; PE = 24). C-reactive protein (CRP) was determined by CRP ultrasensitive method (Control = 7; PE = 18) was performed using sera pregnant women. Women with preeclampsia had higher weight at the beginning of the pregnancy (p=0.0171) and lower gestational age at delivery (0.0008). Classical monocytes were decreased in preeclampsia but not intermediate or non-classical monocytes. The frequency of IL-1R2 pro inflammatory cytokine receptors is decreased in women with PE only in the subpopulation of non-classical monocytes (p = 0.0011). TNF-?R1 receptor and IL-6R, had a decreased frequency in the three subpopulations of monocyte (classic, intermediate and non-classical) when compared to women with normal pregnancy. An increase in IL-1R2 receptor in TCD4+ lymphocytes, but a decrease in TNF-receptor and IL-6R in women with preeclampsia were found. No differences in the frequency of those receptors in CD3+/CD8+ in preeclampsia. There was no difference in C-reactive protein in preeclampsia. The reduction in the amount of IL-1R2, TNF- ?R1 and IL-6R monocytes and lymphocytes can be involved in the regulation of inflammation observed in preeclampsia, contributing to disease.

Made available in DSpace on 2014-12-17T15:16:20Z (GMT). No. of bitstreams: 1 LianeBM_DISSERT.pdf: 2657175 bytes, checksum: 697315a6a5057be81e8e63dbfed5fef4 (MD5) Previous issue date: 2013-12-18 / Exercise-induced muscle damage mainly affects individuals who returned to physical activity after a time without practicing it or had some kind of exhaustive exercise, particularly eccentric exercise. To evaluate the effect of cryotherapy and laser therapy in response to muscle damage induced by eccentric exercise on the biceps muscle. This was a randomized clinical trial consisting of 60 female subjects. All subjects initially underwent an evaluation consisting of perimetry, measurement of pain sensation (via algometry and visual analogue scale), electromyography and dynamometry. Then the subjects performed an exercise protocol on the isokinetic dynamometer consisting of 2 sets of 10 eccentric elbow flexors contraction at 60 ?/s. Completed this protocol, an intervention was held according to a previously random group distribution: control group (no intervention), cryotherapy group and laser therapy group. Finally, subjects were re-evaluated immediately and 48 hours after the intervention protocol, except for Visual Analogue Scale (VAS), which was also evaluated 24 hours after exercise. The circumference of the limb, the pain sensation (VAS and algometry), the muscle activation amplitude (via Root Mean Square - RMS), median frequency, peak torque normalized per body weight, average peak torque, power and work were analyzed. The median frequency immediately after the intervention protocol on the cryotherapy group was the only variable that showed inter and intra-group differences; the remaining variables showed only intragroup differences. The perimetry values did not change immediately after the protocol on the groups which underwent cryotherapy and laser therapy, however, there was an increase after 48 hours; algometry values decreased in all groups for 48 hours and the VAS values increased 24 and 48 hours also for all groups. Regarding RMS no significant change was observed. For dynamometry, peak torque normalized per body weight and average peak torque had a similar behavior, with a reduction in the post protocol that has remained after 48 hours. For the power and work, a decrease was observed immediately after the protocol with a further reduction after 48 hours. Cryotherapy and laser therapy does not alter the muscle damage response, except for the perimetry values immediately after exercise. / Contextualiza??o: O dano muscular induzido pelo exerc?cio afeta principalmente indiv?duos que retornaram ? atividade f?sica ap?s um tempo sem pratic?-la ou realizaram algum tipo de exerc?cio exaustivo, principalmente exerc?cios exc?ntricos. Objetivo: Avaliar o efeito da crioterapia e da laserterapia na resposta ao dano muscular induzido pelo exerc?cio exc?ntrico no m?sculo b?ceps braquial. Metodologia: Trata-se de um ensaio cl?nico e randomizado composto por 60 sujeitos do sexo feminino. Todos foram submetidos inicialmente a uma avalia??o composta por perimetria, mensura??o da sensa??o dolorosa (por meio de algometria e escala visual anal?gica), eletromiografia e dinamometria. Em seguida as volunt?rias realizaram um protocolo de exerc?cio no dinam?metro isocin?tico composto de 2 s?ries de 10 contra??es exc?ntricas a 60?/s para os flexores de cotovelo. Finalizado o protocolo, foi realizada uma interven??o de acordo com o grupo previamente e aleatoriamente distribu?do: grupo controle (sem realizar interven??o), grupo crioterapia e grupo laserterapia. Por fim, os indiv?duos foram submetidos a reavalia??es imediatamente e 48 horas ap?s o protocolo de interven??o, exceto para Escala Visual Anal?gica (EVA), que tamb?m foi avaliada 24 horas ap?s o exerc?cio. Foram analisadas a circunfer?ncia do membro, a sensa??o dolorosa (EVA e algometria), a amplitude de ativa??o muscular (atrav?s do Root Mean Square-RMS), a frequ?ncia mediana, o pico de torque normalizado pelo peso corporal, o pico de torque m?dio, a pot?ncia e o trabalho. Resultados: A frequ?ncia mediana no p?s imediato do grupo crioterapia foi a ?nica vari?vel que apresentou diferen?a inter e intragrupo; as demais vari?veis analisadas s? apresentaram diferen?as intragrupo. Os valores da perimetria n?o se alteraram no p?s imediato para os grupos que realizaram crioterapia e laserterapia, no entanto, houve um aumento ap?s 48 horas; os valores da algometria reduziram nas 48h para todos os grupos e os da EVA aumentaram em 24 e 48 horas tamb?m para todos os grupos. Em rela??o ao RMS n?o foi observada altera??o significativa. Para dinamometria, o pico de torque normalizado pelo peso corporal e o pico de torque m?dio tiveram um comportamento similar, com uma redu??o no p?s imediato que se manteve ap?s 48 horas. J? para a pot?ncia e o trabalho, foi observada uma diminui??o nos valores do p?s imediato com uma nova redu??o ap?s 48 horas. Conclus?o: A crioterapia e a laserterapia n?o alteram a resposta ao dano muscular, exceto para os valores de perimetria imediatamente ap?s o exerc?cio

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2018-02-15T12:44:59Z No. of bitstreams: 1 DanielCostaDeSouza_DISSERT.pdf: 1625998 bytes, checksum: 824c5486dd368ffb01c3d3a1163f37f1 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2018-02-19T21:26:44Z (GMT) No. of bitstreams: 1 DanielCostaDeSouza_DISSERT.pdf: 1625998 bytes, checksum: 824c5486dd368ffb01c3d3a1163f37f1 (MD5) / Made available in DSpace on 2018-02-19T21:26:44Z (GMT). No. of bitstreams: 1 DanielCostaDeSouza_DISSERT.pdf: 1625998 bytes, checksum: 824c5486dd368ffb01c3d3a1163f37f1 (MD5) Previous issue date: 2017-07-10 / Introdu??o: O excesso de gordura corporal ? associado ? inflama??o cr?nica de baixo grau e uma maior incid?ncia de doen?as infecciosas. Estudos recentes, indicam que o exerc?cio intervalado de alta intensidade (EIAI) ? uma estrat?gia eficiente em fun??o do tempo para melhorar par?metros de sa?de de indiv?duos com obesidade. No entanto, pouco ? conhecido sobre o efeito de uma sess?o de EIAI no equil?brio de citocinas pro e anti-inflamat?rias em obesos. Objetivo: O objetivo do presente estudo foi comparar uma ?nica sess?o de EIAI e exerc?cio cont?nuo de moderada intensidade (ECMI) sobre os n?veis s?ricos de interferon-y (INF-y), interleucina 4 e 6 (IL-4) (IL-6) e INF-y/IL-4 em homens com obesidade. M?todos: Dez homens com obesidade (IMC>30 kg/m?) foram submetidos a tr?s sess?es experimentais com uma semana de intervalo em ordem aleat?ria: 1) EIAI: 10 x 60 s a 90% da FCm?x alternados por 60 s de recupera??o ativa; 2) ECMI: 20 min a 70% da FCmax; 3) Controle. As coletas de sangue para analisar os n?veis s?ricos de citocinas foram realizadas nos momentos pr?, p?s e 60 min ap?s as sess?es de exerc?cio ou controle. Os dados foram apresentados em m?dia ? DP. ANOVA fatorial com medidas repetidas e post hoc de Bonferoni foi utilizado para avaliar as diferen?as entre os momentos e condi??es de exerc?cio. O n?vel de signific?ncia aceito foi de P< 0.05. Resultados: O EIAI reduziu os n?veis de INF-y imediatamente ap?s o exerc?cio (41,09 ? 14,99; P=0,032) e 60 min ap?s o exerc?cio (43,45 ? 11,76; P=0,003) em rela??o ao pr?-exerc?cio (46,64 ? 13,14), ao mesmo tempo que promoveu aumento nos n?veis de IL-4 imediatamente ap?s o exerc?cio (36,47 ? 11,09; P=0,007) em rela??o ao pr?-exerc?cio (32,04 ? 8,5). O ECMI promoveu aumento nos n?veis de INF-y imediatamente ap?s o exerc?cio (47,48 ? 8,42; P=0,025) e 60 min ap?s o exerc?cio (50,13 ? 7,99; P=0,004) em rela??o ao valor pr?-exerc?cio (44,21 ? 8,11). Ambas as condi??es de exerc?cio aumentaram os n?veis de IL-6 at? 60 min ap?s o exerc?cio (P<0.05). A raz?o INF-Y/IL-4 reduziu imediatamente ap?s (1,24 ? 0,60; P=0,002) e 60 min ap?s o exerc?cio (1,32 ? 0,53; P=0,005) em rela??o ao pr?-exerc?cio (1,58 ? 0,64) apenas para o EIAI. Conclus?o: Uma sess?o de EIAI induziu um padr?o de resposta anti-inflamat?ria e est? associado a preju?zos na resposta imune intracelular contra pat?genos. Por outro lado, uma breve sess?o de ECMI induziu altera??es no padr?o de citocinas seguindo um padr?o pr?-inflamat?rio o que pode favorecer ? melhora da resposta imune intracelular em homens com obesidade. / Introduction: The excess of body fat is associated with chronic low-grade inflammation and high rates of infectious disease. Emerging evidences indicate that high intensity interval exercise (HIIE) is a time-efficient approach to promote health in obese population. However, little is known about the influence of HIIE on pro and anti-inflammatory cytokine balance in obesity. Purpose: Our purpose was to compare the acute effects of HIIE and moderate-intensity continuous exercise (MICE) on cytokine levels, include interferon-y (INF-y), interleukin 4 and 6 (IL-4) (IL-6) levels and INF-y/IL-4 ratio in obese males. Methods: Ten obese males (BMI>30 kg/m?) were submitted into two experimental sessions with a week interval in a randomized order: 1) HIIE: 10 x 60 s at 90% of HRm?x interspersed by active recovery; 2) MICE: 20 min at 70% of HRmax;. Cytokines was analyzed before, immediately after and 60 min after-exercise. Data was presented in mean ? SD. ANOVA 2-way with repeated measures and post hoc Bonferoni was used to assess differences between moments and exercise conditions. Statistical significance was accepted at a p value of ? 0.05. Results: The HIIE results in decreased INF-Y levels immediately after-exercise (41,09 ? 4,74; P=0,032) and 60 min after-exercise (43,45 ? 3,72) (P=0,003) compared with before-exercise (46,64 ? 4,15), while an significant elevation in IL-4 levels was observed immediately after-exercise (36,47 ? 3,5) (P=0,007). The MICE results in increase of INF-Y levels after exercise (P=0,025) and 60 min post-exercise (P=0,004). Both exercise conditions results in increase of IL-6 levels after exercise (P<0.05). The INF-Y/IL-4 ratio decreases immediately after (P=0,002) and 60 min after-exercise (P=0,005) only for HIIE. Conclusion: HIIE induces imbalance in INF-Y/IL-4 ratio 60 min after exercise following an anti-inflammatory pattern. For other hand, MICE did not promote imbalance in INF-Y/IL-4 to 60 min after exercise in obese males.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-04-17T23:20:36Z No. of bitstreams: 1 BrunaSilvaOliveira_TESE.pdf: 2168230 bytes, checksum: e104821a58eb464892a9329229db3c08 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-04-20T23:37:21Z (GMT) No. of bitstreams: 1 BrunaSilvaOliveira_TESE.pdf: 2168230 bytes, checksum: e104821a58eb464892a9329229db3c08 (MD5) / Made available in DSpace on 2017-04-20T23:37:21Z (GMT). No. of bitstreams: 1 BrunaSilvaOliveira_TESE.pdf: 2168230 bytes, checksum: e104821a58eb464892a9329229db3c08 (MD5) Previous issue date: 2016-11-25 / Introdu??o: o comprimento do tel?mero (TL) tem sido apontado como um poss?vel biomarcardor do envelhecimento celular, pois ocorre encurtamento fisiol?gico e progressivo do seu tamanho com o decorrer das replica??es celulares. Adicionalmente a esse encurtamento fisiol?gico, a disfun??o do TL tamb?m ? favorecida pela exposi??o ao estresse oxidativo, a inflama??o e ap?s o estresse psicossocial cr?nico. Existe ainda uma lacuna de conhecimento sobre as altera??es do TL durante o curso de vida em popula??es de mulheres idosas brasileiras, havendo a necessidade de estudos que possibilitem melhor entendimento da influ?ncia de contrastes sociais, condi??es socioecon?micas desfavor?veis, bem como exposi??o ao estresse social cr?nico no TL. Objetivos: 1) desenvolver uma revis?o sistem?tica para explorar as evid?ncias sobre associa??es entre estresse cr?nico durante o curso de vida e TL; 2) investigar poss?veis associa??es entre TL e adversidades na inf?ncia (social e econ?mica) em mulheres idosas com diferentes n?veis de escolaridade; 3) avaliar se o TL est? relacionado com doen?as cr?nicas e biomarcadores inflamat?rios em mulheres idosas; e 4) verificar se tel?meros mais curtos est?o associados com pior desempenho f?sico e maior autorrelato de limita??es funcionais em idosas. Materiais e m?todos: foi desenvolvida uma revis?o sistem?tica seguindo protocolo publicado em 2014. Concomitantemente, realizou-se um estudo observacional anal?tico de car?ter transversal com uma amostra de mulheres (n=106) com diferentes n?veis de escolaridade (ensino m?dio incompleto e ensino m?dio completo) na faixa et?ria de 64-74 anos e residentes no munic?pio de Natal (Rio Grande do Norte). Os dados foram coletados no per?odo de maio de 2014 a mar?o de 2015. A quantifica??o relativa do tamanho dos tel?meros (T/S) de leuc?citos foi realizada por meio da qPCR em tempo real em 83 mulheres. O question?rio padronizado incluiu informa??es sociodemogr?ficas, adversidades na inf?ncia, medidas antropom?tricas, autorrelato de sa?de, fun??o cognitiva, h?bitos de vida, condi??es cr?nicas de sa?de, capacidade funcional e desempenho f?sico (short physical performance battery, velocidade da marcha e for?a de preens?o manual). Foram analisados tamb?m biomarcadores inflamat?rios (interleucina-6 e prote?na c reativa). Para an?lise estat?stica, foram considerados p<0,05 e intervalos de confian?a de 95%. A normalidade dos dados foi verificada por meio do teste de Kolmogorov-Smirnov. Uma vez que o TL apresentou distribui??o n?o normal, foi realizada a transforma??o da medida em logaritmo natural para as an?lises subsequentes. Foram aplicados os testes T de Student para amostras independentes, Qui-quadrado e realizados modelos de regress?o linear m?ltipla ajustados pelos potenciais fatores de confus?o. Resultados: na revis?o sistem?tica, os resultados foram relatados de acordo com o Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Considerando os dezoito estudos inclu?dos na revis?o, no geral, observou-se que indiv?duos expostos ao estresse cr?nico, caracterizado por pobreza, exposi??o ? viol?ncia e cuidar de familiar doente apresentaram tel?meros mais curtos em rela??o aos indiv?duos n?o expostos ?s adversidades. An?lises do estudo transversal sobre TL e curso de vida mostraram que as idosas com ensino m?dio incompleto apresentaram maior TL em compara??o com o grupo de ensino m?dio completo (2.8 ? 0.9 e 2.0 ? 0.9, respectivamente; p = 0,0001). As mulheres que n?o conclu?ram o ensino m?dio foram expostas a mais adversidades na inf?ncia, e entre estas, as que sofreram duas ou mais adversidades apresentavam TL mais longo do que as mulheres expostas a ?1 adversidades (p = 0,03); entre as mulheres com, no m?nimo, ensino m?dio completo, essa diferen?a n?o foi significativa (p = 0,49). Em an?lises ajustadas por idade, escolaridade e abuso parental de ?lcool, observou-se tend?ncia linear de maior TL com maior n?mero de adversidades (p = 0,02) e a diferen?a no TL entre os n?veis de escolaridade permaneceu significativa (p = 0,002). N?o se observou diferen?a entre os grupos educacionais em rela??o ?s seguintes vari?veis: colesterol, triglic?rides, glicemia em jejum, hemoglobina glicada, prote?na c reativa e interleucina-6 (p>0,05). Condi??es cr?nicas de sa?de, medidas antropom?tricas, fatores de risco cardiovasculares e marcadores inflamat?rios n?o foram associados com o TL, mesmo ap?s o ajuste para idade, escolaridade e adversidades na inf?ncia (p>0,05). Igualmente, o TL n?o foi relacionado com nenhuma das vari?veis utilizadas para avaliar o desempenho f?sico e a capacidade funcional (p>0,05). Conclus?es: a rela??o positiva inesperada entre menor escolaridade e adversidades na inf?ncia com TL sugere que os participantes sobreviveram a duras condi??es de vida e que, provavelmente, essas mulheres t?m o TL mais longo em rela??o ao daquelas de sua coorte de nascimento. A aus?ncia de rela??o entre TL e doen?as cr?nicas, risco cardiovascular, inflama??o e desempenho f?sico, n?o deu suporte ? hip?tese de que o TL ? um biomarcador do envelhecimento na popula??o em estudo, por?m corrobora outros estudos que revelaram que o TL pode ser considerado um marcador de longevidade, independentemente de condi??es de sa?de e desempenho f?sico. / Introduction: Telomere length (TL) has been pointed out as a possible biomarker of cellular aging, as its physiological size progressively shortens with the course of cellular replications. In addition to this physiological shortening, TL dysfunction is also stimulated by exposure to oxidative stress, inflammation and after chronic psychosocial stress. There is also a lack of knowledge about TL changes during the course of life in populations of older Brazilian women, and there is a need for studies which foster a better understanding of the influence of social contrasts, unfavorable socioeconomic conditions, as well as exposure to chronic social stress in TL. Objectives: 1) To develop a systematic review to explore the evidence on associations between chronic stress over the life course and TL; 2) To investigate possible associations between TL and childhood adversities (social and economic) in older women with different levels of education; 3) To evaluate whether TL is related to chronic diseases and inflammatory biomarkers in older women; and 4) To verify whether shorter telomeres are associated with poorer physical performance and higher self-reported functional limitations in older adults. Materials and methods: A systematic review was developed following a protocol published in 2014. An observational cross-sectional analytical study was concomitantly carried out with a sample of women (n = 106) with different levels of education (incomplete secondary education and complete secondary education) in the age group of 64-74 years residing in the municipality of Natal (Rio Grande do Norte). Data were collected from May 2014 to March 2015. The relative quantification of leukocyte telomere size (T/S) was performed by real-time qPCR in 83 women. The standardized questionnaire included sociodemographic information, childhood adversities, anthropometric measures, self-reported health, cognitive function, life habits, chronic health conditions, functional capacity and physical performance (short physical performance battery, gait speed and manual grip strength). Inflammatory biomarkers (interleukin-6 and c-reactive protein) were also analyzed. For statistical analysis, p<0.05 and 95% confidence intervals were used. The normality of the data was verified by the Kolmogorov-Smirnov test. Since TL presented non-normal distribution, the transformation of the measure into natural logarithm was performed for subsequent analyzes. Student's t-tests were applied for independent samples, and Chi-square and multiple linear regression models were adjusted for potential confounding factors. Results: The results of the systematic review were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Considering the eighteen studies included in the review, we generally observed that individuals exposed to chronic stress, characterized by poverty, exposed to violence and/or caring for a sick relative had shorter telomeres compared to individuals who were not exposed to adversity. Analyzes of the cross-sectional study on TL and life course showed that the older adults with incomplete secondary education presented higher TL compared to the group of complete secondary education (2.8 ? 0.9 and 2.0 ? 0.9, respectively; p = 0.0001). Women who did not complete high school were exposed to more adversity in childhood, and among them, those who suffered two or more adversities had longer TL than women exposed to ?1 adversity (p = 0.03); among women with at least complete secondary education, this difference was not significant (p = 0.49). In analyzes adjusted for age, educational level and parental alcohol abuse, a linear trend of higher TL for greater number of adversities (p = 0.02) was observed, and the difference in TL between education levels remained significant (p = 0.002). No difference between the education groups was observed for the following variables: cholesterol, triglycerides, fasting glycemia, glycated hemoglobin, c-reactive protein and interleukin-6 (p>0.05). Chronic health conditions, anthropometric measures, cardiovascular risk factors and inflammatory markers were not associated with TL, even after adjusting for age, schooling and childhood adversities (p>0.05). Similarly, TL was not related to any of the variables used to assess physical performance or functional capacity (p>0.05). Conclusions: The unexpected positive relationship between TL and lower education level and childhood adversities suggests that participants survived harsh living conditions and that these women probably have longer TL in relation to others among their birth cohort. The lack of relationship between TL and chronic diseases, cardiovascular risk, inflammation and physical performance did not support the hypothesis that TL is an aging biomarker in the population under study, but corroborates other studies that have shown TL to be considered as a marker of longevity, regardless of health conditions and physical performance.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-06-13T20:29:52Z No. of bitstreams: 1 AndreLuizSilvaDavim_TESE.pdf: 2927049 bytes, checksum: c70bf3fe6cd0580d21ea07690845a8e8 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-06-19T14:43:48Z (GMT) No. of bitstreams: 1 AndreLuizSilvaDavim_TESE.pdf: 2927049 bytes, checksum: c70bf3fe6cd0580d21ea07690845a8e8 (MD5) / Made available in DSpace on 2017-06-19T14:43:48Z (GMT). No. of bitstreams: 1 AndreLuizSilvaDavim_TESE.pdf: 2927049 bytes, checksum: c70bf3fe6cd0580d21ea07690845a8e8 (MD5) Previous issue date: 2017-02-23 / Atualmente os custos no tratamento de pacientes com doen?as inflamat?rias que progridem de forma sist?mica, com destaque para a sepse, s?o muito elevados e representa a maior causa de morte em unidades de terapia intensiva, n?o cardiol?gica, em todo o mundo. No Brasil, a incid?ncia de pacientes com sepse ? cada vez mais frequente. Apesar dos avan?os farmacol?gicos, tecnol?gicos e cir?rgicos, a mortalidade por sepse e/ou doen?as associadas continua alta em todo o mundo, e por isso se busca alternativas terap?uticas de f?cil acesso e baixo custo para conter o avan?o dessa doen?a. Os produtos naturais v?m desempenhando importante papel na ind?stria farmac?utica, pois algumas dessas subst?ncias agem de forma ben?fica sobre o sistema imunol?gico humano. Nos ?ltimos tempos, h? uma crescente investiga??o das poss?veis propriedades biol?gicas e terap?uticas atribu?das ao ?leo de r?-touro, pois esse ?leo vem sendo utilizado de forma indiscriminada pela popula??o no tratamento de diversas doen?as como bronquite, asma, l?quem escleroso, furunculose, cisto seb?ceo e para cicatriza??o de pele e mucosas. Por?m as poss?veis consequ?ncias no consumo excessivo desse ?leo s?o, o aumento da produ??o de eicosanoides derivados do ?cido araquid?nico proinflamat?rio e a defici?ncia na regula??o hep?tica, predispondo ? esteatose podendo progredir para inflama??o hep?tica e fibrose. Muitas hip?teses se baseiam na atua??o dos compostos presentes no ?leo de r?-touro na modula??o da resposta inflamat?ria, impedindo assim a instala??o de inj?rias teciduais. Dessa forma, a microemuls?o apresenta-se como uma poss?vel alternativa para um novo sistema de libera??o de f?rmacos, com o intuito de diminuir a incid?ncia de hepatoxicidade e protegendo o organismo contra instala??o de les?es teciduais em fun??o do quadro s?ptico. Assim, o presente estudo teve como objetivo avaliar o potencial anti-inflamat?rio do ?leo de r?-touro puro e em um sistema microemulsionado em modelo experimental. Neste estudo, foi preparado e caracterizado um sistema microemulsionado (WIV) e, aplicado em ensaios biol?gicos a fim de avaliar o potencial antiinflamat?rio do ?leo puro e em microemuls?o. Foram utilizados o modelo de sepse, induzida pela t?cnica da CLP (cecal ligant puncture), e a les?o muscular induzida pela formalina. Os ensaios foram realizados em modelos murinos, onde os animais foram separados aleatoriamente em grupos e tratados com o ?leo de r?-touro puro e em microemuls?o, atrav?s da t?cnica de gavage para posterior avalia??o do potencial hepatot?xico e anti-inflamat?rio. Para a an?lise do potencial antiinflamat?rio em modelo de sepse, foram realizadas lavagens bronco alveolares com posterior contagem de c?lulas inflamat?rias e an?lises histopatol?gicas do tecido pulmonar. Para a an?lise no modelo de les?o muscular, foi avaliado extens?o horizontal da pata dos animais, bem como feita a an?lise histopatol?gica do tecido muscular. Para a an?lise do potencial hepatot?xico das subst?ncias, foram avaliados a taxa de sobrevida dos animais p?s-sepse e as an?lises histopatol?gicas dos tecidos hep?ticos dos animais. Quando avaliado a toxicidade do ?leo de r?-touro puro e em sistema microemulsionado, foi observado que no grupo em que foi administrado a microemuls?o (ME), o f?gado teve a arquitetura preservada, mas com sinais cl?nicos de esteatose hep?tica, diferentemente do grupo ?leo de r?-touro puro (OR), que apresentou m?ltiplos focos de necrose hepatoc?tica acompanhado de infiltrado de polimorfonucleares. Esses achados evidenciam um quadro de esteatohepatite, ou seja, um est?gio mais avan?ado e um precursor do carcinoma hep?tico. Quando avaliada a sobrevida dos animais, foi observado que no grupo ME a taxa foi significativamente maior quando comparado ao grupo OR. Quando avaliado o potencial antiinflamat?rio da ME e OR em modelo de sepse, foi observado em ambos os grupos potencial de modula??o da resposta inflamat?ria, visto a capacidade de reduzir de forma significativa (P?0.01) a migra??o de leuc?citos para os pulm?es ap?s a indu??o da sepse. Quando analisado a histologia dos tecidos pulmonares dos animais dos dois grupos, foi verificado intenso desgaste nos animais do grupo OR quando comparados com o grupo ME, onde evidenciou-se pouco comprometimento tecidual. No ensaio de les?o muscular, foi observado que o grupo ME e OR apresentaram bom potencial antiedematog?nico at? a segunda hora da indu??o da les?o, quando comparados ao grupo controle (P?0.01), mas n?o sendo observado diferen?as significativas entre os dois grupos at? a vig?sima quarta hora p?s-les?o. Nas an?lises histol?gicas foram observadas maior desgaste no tecido muscular do grupo OR, com intensa presen?a de infiltrado celular (edema) e comprometimento de fibras musculares, n?o sendo observado a mesma intensidade de inj?ria no grupo ME. Assim, conclui-se que o ?leo de r?-touro puro e em sistema microemulsionado apresentam bom potencial anti-inflamat?rio nos modelos avaliados, embora o ?leo puro tenha apresentado alto potencial hepatot?xico, caracterizando que este em um sistema microemulsionado, se mostra com um poss?vel novo sistema de libera??o de f?rmacos (NSLF). / Current costs of treating patients with systemically progressing inflammatory diseases, especially sepsis, are the leading cause of death in non-cardiological intensive care units worldwide. In Brazil, the incidence of sepsis in patients is becoming more frequent. Despite pharmacological, technological and surgical advances, mortality due to sepsis and/or associated diseases remains high worldwide, hence the search for easily accessible and inexpensive therapeutic alternatives to contain the progression of this disease. Natural products have played an important role in the pharmaceutical industry because some of these substances act in a beneficial way on the human immune system. In recent times, there is a growing investigation of the possible biological and therapeutic properties attributed to bullfrog oil, since this oil has been used indiscriminately by the population in the treatment of various diseases, such as bronchitis, asthma, lichen sclerosus, furunculosis, sebaceous cyst, and for healing of skin and mucous membranes. However, the possible consequences of excessive consumption of this oil are increased production of eicosanoids derived from proinflammatory arachidonic acid and deficiency in hepatic regulation, predisposing to steatosis, which may progress to hepatic inflammation and fibrosis. Many hypotheses are based on the performance of the compounds present in bullfrog oil in the modulation of the inflammatory response, thus preventing the onset of tissue injuries. The microemulsion is presented as a possible alternative to a new drug delivery system, in order to reduce the incidence of hepatotoxicity and protect the organism against the installation of tissue lesions as a function of the septic condition. The present study is aimed to evaluate the anti-inflammatory potential of pure bullfrog oil and a microemulsion system in an experimental model. In this study, a microemulsified system (WIV) was determined and characterized, and applied in biological tests to evaluate the anti-inflammatory potential of pure oil and microemulsion. We used the sepsis model, induced by cecal ligant puncture (CLP) technique, and the formalin-induced muscle injury. The tests were performed in murine models, where the animals were randomly separated into groups and treated with pure bullfrog oil and microemulsion, using the gavage technique for further evaluation of the hepatotoxic and anti-inflammatory potential. For the analysis of the anti-inflammatory potential in a sepsis model, bronchoalveolar lavage was performed with subsequent inflammatory cell counts and histopathological analyzes of lung tissue. For the analysis in the muscle injury model, the horizontal extension of the limbs of the animals was evaluated, as well as the histopathological analysis of the muscle tissue. For the analysis of the hepatotoxic potential of the substances, the post-sepsis survival rate and the histopathological analyzes of the hepatic tissues of the animals were evaluated. When evaluating the toxicity of pure bullfrog oil and in a microemulsion system, it was observed that in the group that received the microemulsion (ME), the liver had the architecture preserved, but with clinical signs of hepatic steatosis, unlike the pure bullfrog oil group, which presented multiple outbreaks of hepatocytic necrosis accompanied by polymorphonuclear infiltrates. These findings indicate a picture of steatohepatitis, that is, a more advanced stage and a precursor of hepatic carcinoma. When evaluating the survival of the animals, it was observed that the ME group survival rate was significantly higher when compared to the oil group. When evaluating the anti-inflammatory potential of the ME and the oil group in a sepsis model, the potential for modulation of the inflammatory response was observed in both groups, since the leukocyte migration to the lungs was significantly reduced (P<0.01) after the induction of sepsis. When analyzing the histology of the lung tissues of the animals of both groups, intense wear was observed in the animals of the oil group, when compared with the ME group, where there was little tissue compromise. In the muscle injury test, it was observed that the ME and oil group had good anti-nematode potential until the second hour of injury induction, when compared to the control group (P<0.01), but no significant differences were observed between the two groups until twenty-fourth hour post-injury. In the histological analyzes, greater wear was observed in the oil group muscle tissue, with an intense presence of cellular infiltrate (edema) and muscle fibers involvement, and the same intensity of injury was not observed in the ME group. Thus, it is concluded that pure bullfrog oil and microemulsion system present good anti-inflammatory potential in the evaluated models, although the pure oil showed high hepatotoxic potential, characterizing that in a microemulsified system, it is shown with a possible new drug delivery system (NSLF).

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-11-01T23:16:15Z No. of bitstreams: 1 NataliaCabralSouza_DISSERT.pdf: 6162949 bytes, checksum: a617efb8abda58ca56a363d6c5f97c62 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-11-16T21:48:54Z (GMT) No. of bitstreams: 1 NataliaCabralSouza_DISSERT.pdf: 6162949 bytes, checksum: a617efb8abda58ca56a363d6c5f97c62 (MD5) / Made available in DSpace on 2017-11-16T21:48:54Z (GMT). No. of bitstreams: 1 NataliaCabralSouza_DISSERT.pdf: 6162949 bytes, checksum: a617efb8abda58ca56a363d6c5f97c62 (MD5) Previous issue date: 2017-08-25 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Extratos vegetais s?o aplicados amplamente na medicina popular, principalmente na regi?o Nordeste do Brasil. O extrato das folhas de Turnera subulata e Anacardium occidentale, por exemplo, ? aplicado como alternativa no tratamento de diversas doen?as como diabetes, hipertens?o, dor cr?nica, c?ncer e inflama??es. Entretanto, apesar do seu amplo uso, os efeitos desses compostos ainda n?o est?o bem descritos. Deste modo, buscamos avaliar as propriedades antioxidantes e anti-inflamat?rias dos extratos das folhas de T. subulata e A. occidentale em um modelo de inflama??o in vitro, usando o lipopolissac?rideo como estimulo em macr?fagos da linhagem RAW 264.7. Para tanto, fizemos a quantifica??o de marcadores de resposta inflamat?ria na linhagem, assim como a sua capacidade de modula??o das prote?nas cinases ativadas por mit?geno (p38, ERK? e JNK). Adicionalmente, foram realizados ensaios de viabilidade pela rea??o com o brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetraz?lio e da sulforhodamina B, avalia??o da modula??o em fator de necrose tumoral alfa e interleucina-1?, al?m de ensaios espec?ficos para a avalia??o antioxidante como o de oxida??o de diclorofluoresce?na em tempo real, quantifica??o das esp?cies reativas do ?cido tiobarbit?rico, prote?nas tiol e carbonila??o de prote?nas. Os extratos apresentaram atividades antioxidantes e anti-inflamat?rias, por ser poss?vel observar que o co-tratamento com o extrato das folhas de T. subulata foi capaz de reduzir o estresse oxidativo nas c?lulas, produzido pela resposta inflamat?ria, tal como, possuiu a capacidade de modular diretamente a resposta inflamat?ria, modulando a atividade dos membros das vias prote?nas cinases ativadas por mit?geno. No extrato das folhas de A. occidentale, os resultados tamb?m demostraram atividade antioxidante, que foi observado a partir da diminui??o do dano oxidativo em macr?fagos tratados com as dosagens de 0,5 e 5 ?g/mL do extrato. Al?m disso, esse extrato reverteu os danos oxidativos e os par?metros inflamat?rios induzidos por lipopolissac?rideo nas c?lulas testadas, sendo capaz de inibir a libera??o do fator de necrose tumoral alfa e interleucina-1?. Marcadores inflamat?rios como receptor toll-like 4, receptor para produtos de glica??o avan?ada e CD40, que s?o induzidos por lipopolissac?rideo tamb?m foram modulados. Posteriormente avaliamos as vias de sinaliza??o envolvidas na resposta inflamat?ria mediada por lipopolissac?rideo. O extrato de A. occidentale bloqueou os efeitos do lipopolissac?rideo na fosforila??o de ERK?, SAPK/JNK e P38. Dessa forma, nossos resultados indicam os poss?veis efeitos antioxidantes e anti-inflamat?rios dos extratos aquosos de T. subulata e A. occidentale e demonstram os poss?veis mecanismos biol?gicos respons?veis por esses efeitos. / Plant extracts are widely applied in popular medicine, mainly in the Northeastern Brazil. The leaf extracts of Turnera subulata and Anacardium occidentale, for example, are applied as an alternative in the treatment of lots diseases such diabetes, hypertension, chronic pain, cancer and inflammation. Despite their wide use, the effects of these are still not well described. Thus, we to evaluate the antioxidant and anti-inflammatory properties of leaf extracts of T. subulata and A. occidentale in an in vitro inflammation model of using lipopolysaccharide macrophage RAW 264.7 cells. Therefore, we quantified the inflammatory response markers in the lineage, as well as its ability to modulate the MAPKs (p38, ERK? and JNK). In addition, MTT and SRB viability tests, TNF-? and IL-1? modulation evaluation were performed, as well as specific tests for antioxidant evaluation such as DCFH, TBARS, thiol proteins and carbonylation of proteins. The extracts presented antioxidant and anti-inflammatory activities, and it was possible to observe that co-treatment with the extract of leaf the T. subulata was able to reduce the oxidative stress in the cells, produced by the inflammatory response, the capacity for modulate directly the inflammatory response, altering the activity of MAPK pathway members. In the extract of leaf the A. occidentale the results also showed antioxidant activity, which was observed when the extract decreased the oxidative damage in cells of macrophages treated with the dosages of 0.5 and 5 ?g/mL. In addition, this extract reversed the oxidative damage and inflammatory parameters induced by lipopolysaccharide in the cells tested, being able to inhibit the release of TNF-? and IL-1?. Inflammatory markers such as TLR4, RAGE and CD40 that are induced by LPS were also modulated. Later, we evaluated the signaling pathways involved in the lipopolysaccharide-mediated inflammatory response. The extract of A. occidentale blocked the effects of lipopolysaccharide on the phosphorylation of ERK?, SAPK/ JNK and p38. In this way, our results indicate the possible antioxidant and anti-inflammatory effects of the aqueous extracts of T. subulata and A. occidentale and demonstrate the possible biological mechanisms responsible for these effects.

Submitted by Carla Santos (biblioteca.cp2.carla@bahiana.edu.br) on 2018-11-20T16:41:19Z No. of bitstreams: 1 Rozana Teixeira-Taise (1).pdf: 5571475 bytes, checksum: bbc699a3d1a66dcda27d7c9a36da4b2b (MD5) / Approved for entry into archive by JOELMA MAIA (ebmsp-bibliotecacp2@bahiana.edu.br) on 2018-11-20T18:41:28Z (GMT) No. of bitstreams: 1 Rozana Teixeira-Taise (1).pdf: 5571475 bytes, checksum: bbc699a3d1a66dcda27d7c9a36da4b2b (MD5) / Made available in DSpace on 2018-11-20T18:41:28Z (GMT). No. of bitstreams: 1 Rozana Teixeira-Taise (1).pdf: 5571475 bytes, checksum: bbc699a3d1a66dcda27d7c9a36da4b2b (MD5) Previous issue date: 2018-08-31 / Disfun????o endotelial, inflama????o cr??nica e altera????es no perfil lip??dico (PL) integram a fisiopatologia da Anemia Falciforme (AF). Associa????es entre estes mecanismos e manifesta????es cl??nicas podem definir perfis de gravidade e colaborar para melhor compreens??o da doen??a. Objetivos: Avaliar o n??vel de citocinas e o PL em crian??as e adolescentes com AF e sua associa????o com vari??veis cl??nicas e laboratoriais; comparar o n??vel de citocinas e o PL entre falc??micos tratados e n??o tratados com hidroxiur??ia (HDX). M??todos: Estudo transversal, envolvendo 55 crian??as e adolescentes est??veis com hemoglobina SS, das quais 24 em uso de HDX e 41 crian??as e adolescentes saud??veis, de 6 a 18 anos de idade. Realizadas dosagem das Interleucinas (IL) 1??, 6, 8, 10, 12pq, 17A e TNF-??; dosagem do colesterol total, triglic??rides (TG), LDL-C e HDL-C; dosagem de prote??na C reativa de alta sensibilidade (PCRas). A fun????o endotelial foi avaliada atrav??s da vasodilata????o mediada por fluxo (VMF) da art??ria braquial. Dados do doppler transcraniano foram obtidos em consulta ao prontu??rio. An??lise de cluster hier??rquico (CH) foi realizado para avaliar a diferen??a entre os grupos Resultados: A idade e o sexo foram semelhantes entre os grupos AF HDX n??o; AF HDX sim e grupo controle (p=0,054 e p=0,115 respectivamente). A an??lise de CH demonstrou predom??nio de marcadores inflamat??rios (IL, PCR as, leuc??citos) no grupo AF. As citocinas IL-17A e IL-8 apresentaram correla????o positiva com n??mero de crises vasoclusivas(CVO) e TNF- ?? com n??mero de transfus??es sangu??neas. O grupo AF apresentou n??veis de colesterol total (CT), LDL-c e HDL-c baixos, TG/HDL-c e TG elevados comparados ao grupo saud??vel. TG/ HDL-c se correlacionou positivamente com LDH (rs 0,30 p= 0,047), com contagem de leuc??citos (rs 0,40 p= 0,006), com velocidade do fluxo sangu??neo na art??ria cerebral direita (rs 0,35 p = 0,037) e esquerda (rs 0,361 p=0,026). CT se correlacionou negativamente com PCR as (rs -0,3 p=0,04) e LDL-c com total de transfus??o sangu??nea (rs -0,3 p= 0,032). Falc??micos com TG/HDL-c acima de 2,73 mg/dl apresentaram mais Sindrome Tor??cica Aguda 70,6% vs 29,4% p=0,027, com chance de 3,77 vezes, IC95%(1,135- 12,53) para este evento. Identificado tr??s subfen??tipos: hemol??tico, grupo AF HDX n??o; inflamat??rio, grupo AF HDX sim; grupo saud??vel com fun????o endotelial preservada, aus??ncia de anemia, n??veis mais elevados de IL-10. Conclus??es: Crian??as e adolescentes com AF tratados com HDX, potencialmente mais graves, apresentaram perfil inflamat??rio que se associou a CVO, demonstrando o envolvimento das citocinas na patog??nese da AF. Pacientes n??o tratados com HDX apresentaram perfil hemol??tico associado a eleva????o dos n??veis de TG/HDL-c, demonstrando a associa????o entre metabolismo lip??dico e hem??lise. TG/HDL-C desponta como marcador de les??o vascular atrav??s das associa????es com marcadores de hem??lise, inflama????o, manifesta????es agudas e complica????es da doen??a.