Introdução: Neurocistcercose (NC) é a doença parasitária do SNC mais frequente no mundo. Afeta mais de 50 milhões de pessoas. No entanto, algumas de suas manifestações clínicas, como comprometmento cognitivo e demência, ainda permanecem caracterizadas de modo incompleto, sem que haja estudos controlados disponíveis na literatura até o momento. Objetvos: Investigar a frequência e o perfil clínico do comprometimento cognitivo associado à NC ativa, comparando o desempenho em testes de avaliação cognitiva de pacientes com a doença ao de controles saudáveis (CS) e de pacientes com epilepsia criptogênica (EC). Métodos: Quarenta pacientes (idade média = 39,25 ± 10,50 anos), com diagnóstco de NC ativa segundo critérios absolutos à ressonância magnética (RM) de crânio e sem tratamento antiparasitário prévio foram submetdos à avaliação cognitiva e funcional extensas, sendo comparados a 49 CS e 28 pacientes com EC emparelhados por idade, nível educacional e frequência de crises epilépticas (grupo EC). Resultados: Pacientes com NC apresentaram comprometimento significativo em relação ao grupo CS nos testes que avaliam funções executivas, memória verbal e não verbal, praxia construtiva e fluência verbal (p<0,05). Demência foi diagnosticada em 12,5% dos pacientes com NC de acordo com os critérios do DSM-IV. Os doentes do grupo NC apresentaram desempenho significativamente inferior em testes de memória operacional, memória episódica verbal, funções executivas, nomeação, praxia construtiva e orientação visual-espacial, quando comparados àqueles do grupo EC. Não se encontrou correlação entre as alterações nos testes cognitivos nos pacientes com NC e os achados à RM (carga de doença, tipo e localização das lesões). Conclusões: Comprometimento cognitivo foi muito frequente na amostra de pacientes com NC avaliada, sendo que demência foi identificada em uma proporção significativa dos doentes. Estes dados aumentam o nosso conhecimento sobre a apresentação clínica da NC e sobre seu potencial impacto na saúde pública. / Introducton: Neurocysticercosis (NCYST) is the most frequent CNS parasitic disease worldwide, afecting more than 50 million people. However, some of its clinical findings, such as cognitive impairment and dementia, remain poorly characterized, with no controlled studies conducted so far. We investigated the frequency and the clinical profile of cognitive impairment and dementia in a sample of NCYST patents in comparison to cognitvely healthy controls (HC) and to cryptogenic epilepsy (CE) patents. Methods: Forty treatment-naïve NCYST patients aged 39.25 ± 10.50 years and fulfilling absolute criteria for definitive active NCYST on magnetic resonance imaging (MRI), underwent a comprehensive cognitive and functional evaluation and were compared to 49 HC and 28 CE patients of similar age, educational level, and seizure frequency. Results: NCYST patients displayed significant impairment in executive functions, verbal and non-verbal memory, constructive praxis, and verbal fluency when compared to HC (p<0.05). Dementia was diagnosed in 12.5% of NCYST patients according to the DSM-IV criteria. When compared to CE patients, NCYST patients presented altered working and episodic verbal memory, executive functions, naming, verbal fluency, constructive praxis, and visual-spatal orientation. No correlation emerged between cognitive scores and number, localization or type of NCYST lesions on MRI. Conclusions: Cognitive impairment was ubiquitous in this sample of active NCYST patients. Antepileptic drug use and seizure frequency could not account for these features. Dementia was present in a signifcant proportion of patients. These data broaden our knowledge on the clinical presentations of NCYST and its impact in public health

A Doença de Wilson (DW) é uma moléstia hereditária, caracterizada pela deficiência de excreção do cobre pelo fígado devido à mutação do gene A TP7B. O distúrbio do olfato ocorre com frequência em doenças neurodegenerativas como na doença de Parkinson (DP) e na doença de Alzheimer (DA). A análise do olfato tem sido utilizada como um instrumento útil no diagnóstico diferencial das diversas formas de parkinsonismo degenerativo, e, especialmente, na diferenciação entre DP e tremor essencial. O diagnóstico precoce na DW é a chave para o sucesso do tratamento. Na hipótese de haver comprometimento do olfato em fases iniciais da doença, esse poderia ser um dado a mais para auxiliar no diagnóstico. Até o presente, há apenas um estudo relacionando a DW com a disfunção do olfato. O objetivo deste estudo foi avaliar o olfato em um grupo de pacientes com DW e confrontar com grupo- controle. No presente estudo, foram analisados 37 portadores de DW com manifestação neurológica, 24 portadores de DW sem manifestação neurológica e 59 controles. Todos os indivíduos foram analisados com relação à idade, ao gênero, ao grau de escolaridade, ao uso de tabaco e ao miniexame do estado mental (MEEM), e os portadores de DW foram avaliados quanto ao tempo de doença, tratamento medicamentoso e escore neurológico. O olfato foi avaliado por meio do teste de identificação de odor 8niffin\' 8ticks (88-16 canetas numeradas e quatro opções de resposta para cada uma). Vinte e quatro indivíduos eram pacientes da DW sem manifestação neurológica (45,83% do gênero feminino) e 37 pacientes apresentavam manifestações neurológicas (56,76% do gênero masculino). O qrupo-controle foi composto por 59 indivíduos, 35 (59,33%) do gênero masculino. As médias de- idade foram de 33,38 ± 9,79 anos no grupo de portadores de DW com manifestação neurológica; 29 ± 9,61 anos no grupo de portadores de DW sem manifestação neurológica e 33,81 ± 10,67 anos no grupo-controle. Todos os pacientes com DW estavam em tratamento: 47(77%) com penicilamina, 7 (11,5%) com trientine e 7 (11,5%) com sais de zinco. As médias de respostas corretas no teste de identificação do odor 88-16 foram: 12,03 ± 2, 21 no grupo de portadores de DW com manifestação neurológica, 12, 15 ± 2,07 no grupo de portadores de DW com manifestação hepática e 12,70 ± 2,03 para o grupo- controle. Na avaliação objetiva do olfato com o teste de identificação do odor SS-16, não foi evidenciada diferença significativa entre os três grupos analisados, mas observou-se que o MEEM e o grau de escolaridade influenciaram significativamente no escore do 88-16 na comparação do grupo de pacientes com DW com manifestação neurológica com os outros dois grupos (grupo-controle e o grupo de portadores de DW com manifestação hepática). No presente estudo, não foi evidenciada disfunção olfatória nos pacientes com DW, mas foi observada diminuição da percepção do olfato em alguns pacientes com DW (com e sem manifestação neurológica). Em relação à disfunção olfatória evidenciada em alguns pacientes com DW na presente análise, algumas considerações são pertinentes e poderiam ter influenciado na identificação do olfato neste grupo de pacientes com DW. O acúmulo de cobre e a produção de radicais livres no sistema nervoso central (SNC) podem desencadear processos de neurodegeneração em estruturas envolvidas no olfato, alterações metabólicas, acúmulo de substâncias neurotóxicas (amônia e manganês) e alterações de neurotransmissores, e contribuir para o surgimento da disfunção olfatória / Wilson\'s disease (WO) is a hereditary disease due to a mutation in ATP7B gene, characterized by deficiency of copper excretion by the liver. Smell disorders are frequently encountered in neurodegenerative diseases, such as Parkinson\'s disease (PO) and Alzheimer\'s disease (AO). Smell analysis has been a useful tool for the differential diagnosis of several forms of degenerative parkinsonism, and especially for the differentiation between PO and essential tremor. Early diagnosis in WO is the key for a successful treatment. If there were smell impairment in the early stages of the illness, it could be used as another clue to help on its diagnosis. To the present date, there is only one study connecting WO with smell problems, the aim of this study was to evaluate smell function in a group of WO patients and compare them with a control group. We analyzed 37 WO patients with and 24 WO patients without neurologic symptoms, and 59 controls. Ali subjects were evaluated regarding age, gender, schooling, tobacco use, Mini Mental State Examination (MMSE), and the WO patients were also evaluated regarding duration of the illness, medication and neurologic scoring. Smell was analyzed by means of Sniffin\' Sticks smell identification test (SS-16 numbered pens and four options of answer for each pen). Twenty-four subjects with WO had no neurologic symptoms (45.83% female), and 37 patients had neurologic impairment (56,76% male). The control group was composed by 59 individuais, 35 (59,33%) male. Their age average were 33,38 ± 9,79 years for WO neurologic symptoms; 29 ± 9,61 years for WO without neurologic symptoms; and 33,81 ± 10,67 years for the control group. Ali WO patients were on treatment: 47(77%) with penicillamine, 7(11,5%) with trientine, and 7(11,5%) with zinc salt formulations. The average of correct answers in the SS-16 were: 12,03 ± 2,21 for the WO with neurologic symptoms group; 12,15 ± 2,07 for the WO without neurologic symptoms; and 12,70 ± 2,03 for the control group. In the smell testing with SS-16, there was no significant difference among the three groups, but the MMSE scoring and schooling had a significant influence over SS-16 score when comparing WO with neurologic symptoms patients with the other groups (WO patients without neurologic symptoms and control group). There was no smell dysfunction in WO patients in this study, but diminished smell perception was observed in some WO patients (either with or without neurologic impairment). Regarding smell impairment observed in some WO patients in the current analysis, some considerations must be made that could have influenced smell identification in these individuais. Copper accumulation and free radicais production in the central neNOUS system can trigger neurodegeneration processes in structures involved in srnell perception, metabolic impairment, building up of neurotoxic substances (such as ammonia and manganese), and neurotransmitter disorders, contributing to the emergence of srnell dysfunction

O diabetes melitus tipo 1 é caracterizado por hiperglicemia em decorrência da ausência de secreção de insulina, causada pela destruição de células beta do pâncreas, geralmente por alteração auto-imune. O objetivo deste estudo foi o de conhecer o perfil do paciente diabético tipo 1 em atendimento no CAPE FOUSP, relacionando as complicações as alterações sistêmicas e bucais do diabetes nestes pacientes. Foram coletados dados demográficos, dados da história médica [idade ao diagnóstico, histórico de crise de cetoacidose, hipoglicêmica e hiperglicêmica, maior e menor glicemia já registradas, presença de microangiopatias (retinopatia, doença renal, neuropatia) e macroangiopatias (doença cardiovascular, hipertensão arterial sistêmica), outras doenças sistêmicas, medicação em uso], realizado exame físico extra oral, com aferição da pressão arterial, exame físico intra-oral [para pesquisa de xerostomia, candidíase (pseudomembranosa, eritematosa, leucoplásica, queilite angular), GUNA úlcera aftosa recorrente, herpes simples, síndrome da boca ardente], índice CPOD, índice periodontal comunitário (ICP), índice gengival (IG), presença de cálculo, índice de placa, índice de maloclusão], exames complementares (avaliação do fluxo salivar, aferição da glicemia capilar e teste rápido de hemoglobina glicada) e o preenchimento do questionário Oral health impact profile (OHIP-14). Foram avaliados 26 pacientes, 11 do sexo masculino e 15 do sexo feminino, sendo que a média de idade do diagnóstico variou de 06 meses a 26 anos de idade, o tempo decorrente desde o diagnóstico variou de 1 a 37 anos, 61,53% dos pacientes apresentavam alguma microangiopatia e 27% dos pacientes alguma macroangiopatia. A manifestação bucal mais encontrada foi a xerostomia (61,53%), seguida da queilite angular (23,07%), a média do CPOD foi de 13,26, 50% dos pacientes apresentavam ICP escore 2 e os outros 50% apresentavam escore 3 e 4, 84,61% apresentavam gengivite moderada e a média do IP foi de 2,19. A maloclusão leve foi encontrada em 69% dos pacientes e 92,30% dos pacientes apresentavam fluxo salivar normal, 16 pacientes estavam com hiperglicemia, 23 pacientes apresentavam hemoglobina glicada descompensada e 58% dos pacientes apresentaram um impacto fraco de saúde bucal na qualidade de vida Concluímos que nossos pacientes com DM1 são jovens, com da glicemia e DM descompensados, apresentam a doença há mais de 10 anos, e desenvolveram microangiopatias e macroangiopatias como a doença renal e a hipertensão arterial. Apresentam poucas manifestações bucais, sendo a mais comum a xerostomia; e uma condição bucal satisfatória, em decorrência do acesso ao tratamento odontológico, independentemente da compensação da glicemia. / Diabetes mellitus type 1 is characterized by hyperglycemia due to the absence of insulin secretion caused by destruction of pancreatic beta cells, usually by autoimmune disease. The aim of this study was to establish the profile of the type 1 diabetic patients treated at CAPE FOUSP recognizing the systemic and oral complications of diabetes in these patients. We collected demographic data, medical history [age at diagnosis, history of ketoacidosis, hypoglycemic and hyperglycemic crisis, highest and lowest glycemia recorded, presence of microangiopathy (retinopathy, kidney disease, neuropathy) and macroangiopathy (cardiovascular disease, arterial hypertension), other systemic diseases, drugs in use], and performed blood pressure measurement, and extra and intra oral physical examination [searching for xerostomia, candidiasis (pseudomembranous, erythematous, leucoplakia, angular cheilitis), GUNA, aphthous ulcer, herpes simplex, burning mouth syndrome], DMFT index, community periodontal index (ICP), gingival index (GI), presence of calculus, plaque index, index of malocclusion], complementary tests (measurement of salivary flow and glycemia and a rapid test for glycated hemoglobin) and completing the questionnaire \" Oral health impact profile\" (OHIP - 14). We evaluated 26 patients, 11 males and 15 females, with age of diagnosis from 06 months to 26 years, time elapsed since diagnosis ranged from 1 to 37 years, 61.53 % presented with some microangiopathy and 27 % with macroangiopathy. The most frequent oral manifestation was xerostomia (61.53 %), followed by angular cheilitis (23.07%), the mean DMFT was 13.26, 50 % of patients had ICP score 2 and 50 % had score 3 and 4, 84.61% had moderate gingivitis and mean PI was 2.19. The slight malocclusion was found in 69 % of patients and 92.30 % of patients had normal salivary flow, 16 patients had hyperglycemia, 23 patients had glycated hemoglobin decompensated and 58 % of patients had a weak impact of oral health on quality of life. We conclude that our DM1 patients are young, with blood glucose and DM decompensated with diabetes for over 10 years, and developed microangiopathy and macroangiopathy like kidney disease and hypertension. Few patients have oral manifestations, and the most common is xerostomia, and a satisfactory oral health as a result of access to dental treatment, regardless of the rates of blood glucose.

A doença de Wilson, moléstia hereditária, caracteriza-se pela deficiência de excreção de cobre pelo fígado, originária da mutação do gene ATP7B. As manifestações neurológicas na doença de Wilson são pleomórficas, observando-se distúrbios do movimento com início insidioso e em idade variável - geralmente na segunda ou terceira décadas de vida. Este estudo, dividido em duas partes, descreve as manifestações neurológicas iniciais em 119 pacientes com doença de Wilson (93 casos-índice e 26 familiares acometidos), avaliados entre 1963 e 2004 dos quais 109 foram através de análise retrospectiva dos prontuários médicos, enquanto aos 10 pacientes restantes se dispensou avaliação clínica prospectiva, a partir de 2002. O início dos sintomas ocorreu na média etária dos 19,4 anos (7-37), e o tempo médio do surgimento dos sintomas ao diagnóstico de 1,1 +/- 1,2 anos (0-5 anos). Entre as manifestações neurológicas mais freqüentes, observaram-se: disartria (91%), distúrbios da marcha (75%), risus sardonicus (72%), distonia (69%), rigidez (66%), tremor (60%) e disfagia (50%). A incidência das manifestações coréia e atetose, 16% e 14%, respectivamente, foi baixa. Manifestações atípicas incluíram convulsões (4,2%) e sinais piramidais (3%). A segunda parte do estudo trata da investigação do genótipo ATP7B em 41 pacientes e suas possíveis correlações com o fenótipo neurológico. Encontraram-se 23 mutações distintas, a mais comum das quais (p.A1135fs) com freqüência alélica de 31,7%. Expressiva associação (p<0,05) se deu entre essa mutação e a manifestação disfagia, ainda que limitada por amostra restrita de pacientes. Também sugestiva foi a associação entre a mutação p.A1135fs e quadros neurológicos precoces e graves. Este é o primeiro estudo a comparar o genótipo ATP7B com as manifestações neurológicas na doença de Wilson / Wilson disease, a rare inborn metabolic error, is characterized by deficient hepatic copper excretion, due to mutations in ATP7B gene. Neurological manifestations may vary, although there is commonly a movement disorder starting in the second or third decade of life. This study is divided in two parts, and it describes the neurological manifestations in 119 patients with Wilson disease (93 index cases and 26 affected family members), which were seen between 1963 and 2004 a retrospective analysis in 109 medical records and prospective clinical evaluation in 10 patients since 2002. The average age of symptoms onset was 19.4 years (ranging from 7 - 37 years), and the mean time between the first symptom and diagnosis was 1, 1 +/- 1, 2 years. The most frequent neurological manifestations observed were: dysarthria (91%), gait disturbance (75%), risus sardonicus (72%), dystonia (69%), rigidity (66%), tremor (60%), and dysphagia (50%). Less frequent manifestations were chorea (16%), and athetosis (14%). Rare neurological presentations were seizures (4,2%), and pyramidal signs (3%). In the second part of this study, we ascertain ATP7B genotype correlations with distinct neurological phenotypes in 41 Wilson disease patients. A total of 23 distinct mutations were detected, and the p.A1135fs frameshift had the highest allelic frequency (31.7%). An association between a p.A1135fs mutation and dysphagia was detected (p<0, 05), but the limited number of patients restricts valuable conclusions. This analysis also suggests an association between this mutation and early and severe neurological presentation. This present study is the first one to evaluate an ATP7B genotype correlation with specific neurological profile in Wilson disease

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2016-09-13T14:20:21Z No. of bitstreams: 1 Maria Izabel de Azevedo Marques Birolli.pdf: 1498403 bytes, checksum: 5547b14f6483d57aec5344eb6cf3f16b (MD5) / Made available in DSpace on 2016-09-13T14:20:21Z (GMT). No. of bitstreams: 1 Maria Izabel de Azevedo Marques Birolli.pdf: 1498403 bytes, checksum: 5547b14f6483d57aec5344eb6cf3f16b (MD5) Previous issue date: 2016-04-15 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The thesis is a study on the current youth, more specifically about the generational gap experienced by young people, with the object of study the Jornadas de Junho de 2013 (June 2013 Journey) in Brazil. My hypothesis is that the generations of young people who which command the many street manifestations and in digital networks are experiencing another moment of "revolt", but also reveals some signs of political experiences of the '60s generation, which return to the youth movements, where many of them were born update and reinterpreted, as is the case of environmentalism, feminism, the struggles against racism and the problem of representation in politics. The June 2013 Journey and its consequences were also understood as a social explosion of a social resentment, accumulated frustrations of past generations that gave rise recently to a polarization in the common sense of politics in Brazil. This polarization also affects youth with its striking presence, if no defining in today's conflicts in the networks, on the streets and in recent ideological debates, presented as two ideal types: a generation "neoconservative" and other "naturalistic" / Essa tese é um estudo sobre a juventude atual, mais especificamente sobre a brecha geracional vivida pelos jovens, tendo como objeto de estudo as Jornadas de Junho de 2013, no Brasil. Minha hipótese é que as gerações de jovens que comandam as muitas manifestações nas ruas e nas redes digitais estão experimentando outro momento de “revolta”, mas que revela também alguns sinais de permanências das experiências políticas da geração dos anos 60, as quais retornam para os movimentos juvenis, onde muitas delas nasceram reatualizadas e reinterpretadas, como é o caso do ambientalismo, do feminismo, das lutas antirraciais e do problema da representação na política. As Jornadas de Junho de 2013 e seus desdobramentos foram também compreendidos como explosão de um ressentimento social, acumulados das frustrações das gerações passadas que deram origem recentemente a uma bipolarização no senso comum da política no Brasil. Essa bipolarização afeta também a juventude com sua presença marcante, senão definidora nos atuais conflitos nas redes, nas ruas e nos debates ideológicos recentes, apresentados na forma de dois tipos ideais: uma geração “neoconservadora” e outra “naturalista”

A Síndrome de Sézary (SS) é um dos tipos mais comuns de linfoma cutâneo de células T (CTCL). Esta síndrome é caracterizada por eritrodermia, linfadenopatia generalizada e presença de células tumorais na pele, linfonodos e sangue periférico. A imunidade do hospedeiro está comprometida nesta síndrome, contudo, estudos relacionados à imunidade inata, particularmente sobre as células Natural Killer (NK) são mais escassos. As células NK exercem um papel essencial na resposta imune antitumoral. A proposta deste estudo é caracterizar o perfil fenotípico associado à ativação e inibição das células NK e a capacidade de secreção de citocinas em resposta aos agonistas de receptores Toll-like (TLR), TLR4, TLR7/TLR8 e TLR9 em pacientes com SS. Foram selecionados 14 pacientes com SS (7 homens, 7 mulheres), com 48-85 anos de idade provenientes do Ambulatório de Linfomas Cutâneos do Hospital das Clínicas da Faculdade de Medicina da USP, e um grupo controle com 22 indivíduos sadios (11 homens, 11 mulheres, idade de 48-75). Os resultados evidenciaram diminuição percentual de células NK CD56dim do sangue periférico dos pacientes SS, bem como baixa expressão de marcadores de ativação, NKG2D e NKG2C. A forma solúvel dos ligantes de NKG2D, MICB e MICA solúvel (sMICA/MICB), foi detectada em níveis séricos elevados para sMICB, e sMICA foi detectado em apenas 2 pacientes. Houve uma correlação negativa entre os níveis de sMICB e o percentual de células NK CD56brightCD16 NKG2D+. O perfil de secreção de citocinas das células NK, mostra, já na condição sem estímulo, um aumento percentual de TNF e CD107a em células NKCD56dim de pacientes com SS. Após o estímulo com os agonistas de TLR7/TLR8 houve um aumento na produção de CD107a e TNF nas células NKCD56bright e de TNF para as células NKCD56dim. Na produção de citocinas induzidas por agonistas de TLRs nos sobrenadantes de células mononucleares, foi observado que os agonistas TLR2 e TLR4 foram capazes de estimular a produção de IL-6, TNF e IL-10 enquanto o agonista de TLR7/8 mostrou um efeito adjuvante para a secreção de IFN-alfa, IFN-y e IL-10. Além disso, foi observado aumento de expressão de RNAm para TLR2 em células mononucleares avaliada por PCR em tempo real, como também para os fatores relacionados à resposta antiviral, como interferon tipo I (IFN- alfa), receptor de IFN-beta e interferon tipo III (IFN- ) em pacientes com SS. Quanto aos níveis séricos de citocinas, foi detectado aumento de IL-5 (citocina Th2), IL-6 (pró-inflamatória) e IL-10 (reguladora) nos SS, não diferindo quanto aos níveis de IL-1beta, IL-2, IL-17a, TNF e TGF-beta em relação ao grupo controle. Os resultados mostram que há uma diminuição percentual de células NK CD56dim, alteração da expressão dos receptores de ativação e elevação de ligantes solúveis que podem bloquear a ativação das células NK nos pacientes com SS. Além disto, as células NK exibem diminuição da produção de IFN-alfa, que contribuem na diminuição da resposta Th1. Há uma baixa responsividade das células NK aos ligantes de TLRs. Contudo, há um efeito adjuvante dos ligantes de TLRs em células mononucleares dos pacientes com SS, sendo que os agonistas de TLR2/4 e TLR7/8 foram capazes de restaurar parcialmente a produção de citocinas. Os resultados evidenciam que nos pacientes com SS, apesar da redução percentual das células NK, essas células são funcionais, mas que podem ser bloqueadas pelos ligantes solúveis de receptores de ativação. O uso de ligantes de TLRs pode ser uma estratégia para potencializar a produção de citocinas na Síndrome de Sézary / Sézary syndrome (SS) is one of the most common types of cutaneous T-cell lymphoma (CTCL). This syndrome is characterized by erythroderma, generalized lymphadenopathy and presence of tumor cells in the skin, lymph nodes and peripheral blood. Immunity of the host is compromised in syndrome, a study has related an innate immunity, particularly in Natural Killer (NK) cells are more scarce. NK cells play an essential role in the antitumor immune response. The aim of this study is to characterize the phenotypic profile associated with the activation and inhibition of NK cells and cytokine secretion capacity in response to the TLR4, TLR7 / TLR8 and TLR9 receptor agonists in SS patients. METHODS: We selected 14 patients with SS (7 men, 7 women, 48-85 years old) from the Cutaneous Lymphoma Outpatient Clinic of the Medical School of USP, and a control group with 22healthy individuals (11 men , 11 women, 48-75 years old). The results showed a decrease in CD56dim NK cells in the peripheral blood of SS patients, as well as low expression of activation markers, NKG2D and NKG2C. The soluble form of NKG2D, MICB and soluble MICA (sMICA/MICB) ligands was detected at high levels in serum for sMICB, and sMICA was detected in only 2 patients. There was a negative correlation between sMICB levels and the percentage of NK cells CD56brightCD16 NKG2D+. The cytokine secretion profile of NK cells, in the unstimulated condition, showed an increase of TNF and CD107a in NKCD56dim cells of SS patients. Upon stimulation of TLR7 / TLR8 agonists, CD107a and TNF production was higher in NKCD56bright cellsandforTNF in CD56dim cells.The agonists TLR2 and TLR4 in NK cells were able to stimulate the production of IL-6, TNF and IL-10,, while TLR7/8 agonist showed an adjuvant effect for secretion of IFN-alfa, IFN-y e IL-10. In addition, increased expression of TLR2 mRNA was observed in mononuclear cells evaluated by real-time PCR, simirlaly for factors related to antiviral response, such as interferon type I (IFN-alfa), IFN-Type III receptor (IFN - ) in patients with SS. Forserum levels of cytokines, IL- 5 (cytokine Th2), IL-6 (proinflammatory) and IL-10 (regulatory) were detectedhigher in SS, not differing in levels of IL-1beta, IL-2 , IL-17a, TNF and TGF-beta in relation to the control group. The results show that, there is a percentage decreased of CD56dim NK cells, alteration in activation receptor expression and elevation of soluble ligands that block theactivation of NK cells in SS patients. In addition, NK cells exhibit decreased IFN-? production, thatcontribute to the decrease in Th1 response. There is low responsiveness of NK cells to TLR ligands. However, there is an adjuvant effect of TLR ligands on mononuclear cells of SS patients, with TLR2/4 and TLR7 / 8 agonists is able to partially restore cytokine production. The results show that patients with SS, despite the percentage reduction of NK cells, these cells are functional, but can be blocked by soluble ligands of activation receptors. The use of TLR ligands may be a strategy to potentiate a production of cytokines in Sézary Syndrome

葡萄膜炎是一組複雜的眼內炎性疾病，可導致嚴重的視力損害，約占世界範圍內工作年齡人群組致盲眼病的10%。孫然治療上已取得一定的進步，但找尋安全有效的治療方式仍是一個臨床難題。基於解剖學分類，葡萄膜炎分為前葡萄膜炎、中葡萄膜炎、后葡萄膜炎和全葡萄膜炎。其中，前葡萄膜炎 (AU) 為最常見的臨床形式。此外，基於病因學葡萄膜炎也可被歸類為感染性和非感染性兩大亞型。作為一種炎症性疾病，已有研究表明許多內源性的免疫機制及遺傳因素參與葡萄膜炎的形成。 / 基於對葡萄膜炎疾病進程的深入瞭解，兩條主要潛在的致病通路：T細胞反應途徑和補體系統顯示在分子水平與疾病密切相關。本研究涉及參與上述兩通路的諸多因子，旨在調查葡萄膜炎的遺傳易感性，揭示潛在致病機理，以及發現新的臨床診斷標記物。 / 本研究共納入501名參與者，包括98名AU患者，95名非感染性中後葡萄膜炎 (NIPU) 患者，病例收集自香港眼科醫院及威爾斯親王醫院。此外，308名年齡50歲以上，排除了主要眼科疾患及系統性免疫疾病的健康人被招募為對照組。全面詳細記錄病人資料及臨床信息。進一步剖析葡萄膜炎疾病特點及補體通路參與程度，深入研究補體基因的累加效應及相互作用，以期發現臨床標記物。最後，採用基因型表型相關性分析，探索其與疾病嚴重程度和進展的關係。 / 研究1：系統性綜述在葡萄膜炎基因學研究上的最新發現，研究表明多種基因與葡萄膜炎疾病相關，所涉基因包括白介素、趨化因子、腫瘤壞死因子，以及參與補體和氧化途徑的相關基因。我們廣泛調查了葡萄膜炎的遺傳易感性。基因多態性選擇基於疾病的免疫及炎性特徵。（1）Interleukin與CFH基因，分別參與T細胞反應及補體通路。（2）CFB，CFH的拮抗因子，共同參與了補體旁路的調控。（3）調查C1INH(SERPING1) 因子，闡明補體經典通路在葡萄膜炎形成中的作用。（4）C3和C5基因，分別作為補體系統的“中心“因子及下游調控因子，其與葡萄膜炎的相關性被深入調查。 / 研究 2：首先探索性地調查免疫相關基因的單核苷酸多態性，包括CFH，KIAA1109 與 IL27 基因，我們的結果顯示 CFH 基因多態性 (rs800292，rs1065489) 與前葡萄膜炎顯著相關。更重要的是，CFH-rs1065489 TT基因型被確認為臨床標記物，此基因型攜帶者表現更高的葡萄膜炎復發頻率。此外，易感基因與HLA-B27的交互作用以及性別敏感性差異亦被發現。本研究的第二部份，此三個候選基因在另一個葡萄膜炎亞組NIPU中被進一步調查，CFH基因多態性 (rs800292，rs1065489) 與NIPU相關。KIAA1109-rs4505848也被發現與白塞氏病密切相關。此外，該基因多態性亦表現性別差異，較之對照組，顯性基因型頻率在男性NIPU組表現較高(GG/AG vs. AA)。 / 研究 3：CFB，作為CFH的拮抗因子，共同參與補體旁路的調控，其編碼基因被進一步調查。在AU研究中，位於C2/CFB區域的rs1048709被發現與其密切相關，該遺傳敏感性受HLA-B27影響。此外，我們還發現一個單體型 (AATA) 以及CFH與CFB的疊加效應均可導致AU風險度增高。同時，攜帶rs1048709(AG) 基因型患者傾向于更高程度的前房細胞數及KP比例。在NIPU研究中，類似的與CFB基因上的不同易感位點rs4151657相關性亦被檢測到。 / 研究 4, 5, 6: 在隨後的研究中，參與補體通路的其他三個候選基因 (SERPING1，C3和C5) 被進一步評估，儘管多種深入的分析方法被應用，但均未顯示出與疾病明確的相關性。 / 綜上，我們的結果首次揭示補體系統及其分子因素在葡萄膜炎進程中起著至關重要的作用。參與補體旁路調控的細胞因子 CFH 與 CFB，被確認為疾病風險因素。此外，分別參與補體經典通路或下游調控體系的其他三個候選基因 SERPING1(C1INH)，C3 和 C5， 以及參與T細胞反應通路的IL2_21區域和IL27基因在葡萄膜炎的發生發展中所起作用有限。因此，將來對於葡萄膜炎基因學及免疫學的研究應著眼于補體系統及其旁路途徑。 / Uveitis is a group of heterogeneous ocular inflammatory diseases with complex phenotypes, which causes substantial visual impairment and accounts for about 10% of blindness worldwide among the working age group. Despite considerable progress in treatment, safe and effective management is still a clinical challenge. Uveitis can be anatomically classified as anterior, intermediate, posterior, and panuveitis, anterior uveitis (AU) is the most common form. Based on etiology, uveitis can be also categorized as infectious and noninfectious subtypes. Uveitis is generally accepted as an inflammatory condition and regulated by various endogenous immunological mechanisms. Moreover, uveitis can occur in individuals with genetic predisposition coupled with environmental factors. / Based on our understanding of the critical checkpoints in the uveitis process, two major pathways, T-cell response and complement system, appear to be most related to uveitis in the molecular level. We therefore target on several molecular factors involved in the two major pathways to evaluate the genetic impact on susceptibility to uveitis, reveal potential disease mechanisms, and discover diagnostic markers. / We recruited a total of 501 unrelated Chinese individuals at the Hong Kong Eye Hospital and the Prince of Wales Hospital in Hong Kong, including 98 AU patients, 95 patients with noninfectious intermediate and posterior uveitis (NIPU), and 308 control subjects aged ≥ 50 years without major eye diseases or any systemic immune-related disorders. Clinical information and demographic conditions of the patients were documented. We moved on to depict the disease profile and estimate the contribution of each complement activation pathway in uveitis process. We also conducted interaction analysis among the complement factor genes to reveal the putative clinical markers for uveitis. Genotype-phenotype correlations were performed to explore their relationships with the disease severity and progression. / Study 1: In a systemic review to explore recent genetic findings in uveitis susceptibility, we found several genes persistently associated with uveitis and involved in various pathways. They are genes expressing interleukin, chemokine, tumor necrosis factor, and genes involved in complement and oxidation pathways. Genetic polymorphisms were selected based on the immunological and inflammatory properties of uveitis. (1) Interleukin and CFH genes, involving in the T-cell response and complement system respectively. (2) CFB, as a competitor of CFH, involved in the alternative pathway of complement cascade together. (3) Investigation of C1INH (SERPING1) in uveitis, with a view to elucidating the involvement of the classic pathway of complement cascade in uveitis development. (4) Evaluation of C3 and C5 genes in uveitis, due to their respective role of center component and downstream factor in the complement cascade. / Study 2: Genetic variations in the CFH, KIAA1109 and IL27 genes were examined. Our results showed an association between AU and CFH polymorphisms (rs800292 and rs1065489). The frequency of the CFH-rs800292 184G allele and GG homozygosity was higher in female patients than in controls. CFH-rs1065489 TT genotype was identified as a clinical marker associated with higher uveitis recurrence frequency. Interactions with HLA-B27 status in AU patients and different gender susceptibility were observed. In the second part of this study, these three candidate genes were examined in the other uveitic entity, NIPU, in our study cohort. CFH gene polymorphisms (rs1065489 and rs800292) were associated with NIPU patients. Specific association between KIAA1109-rs4505848 polymorphism and Behçet’s disease was identified. There was also gender specific genetic difference. The dominant genotype of KIAA1109-rs4505848 in male NIPU patients was significantly more frequent than in male controls (GG/AG vs. AA). / Study 3: CFB, a competitor of CFH and participated in the same complement alternative pathway, was investigated. SNP rs1048709 in the C2/CFB region was associated with AU, and this genetic influence was affected by HLA-B27 status. Furthermore, one haplotype block across CFB (AATA) significantly predisposed AU with an increased risk of 1.97 (95% CI: 1.41-2.76; Pcorr=0.0005). Joint effects of CFB-rs1048709 with (CFH-rs800292 and CFH-rs1065489) were identified to be at a risk of 7.48 and 7.0 respectively. In addition, patients carrying rs1048709 (AG) were predicted to develop a higher degree of anterior chamber cells and higher proportion of keratic precipitate (KP) during AU course. For NIPU, association with CFB was detected for a different SNP, rs4151657, in female patients only. / Studies 4, 5, and 6: Three candidate genes (SERPING1, C3 and C5) across the complement cascade were orderly evaluated in the whole study cohort of AU, NIPU and controls. They did not show any significant associations with both two uveitis entities, although multiple in-depth analyses have been performed. / Collectively, our results provide evidence for the involvement of the complement system in the disease pathogenesis of uveitis. CFH and CFB, involved in the complement alternative pathway, are identified as genetic risk factors for uveitis. Other complement pathway genes, SERPING1 (C1INH), C3 and C5, as well as IL2_21 region and IL27 involving in the T-cell response, confer either no or limited risk for the development of uveitis. Future genetic and immunologic investigations in uveitis should therefore be focused on the complement system and the alternative pathway. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Yang, Mingming. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 148-163). / Abstracts also in Chinese. / Title page --- p.i / Abstract --- p.iii / 摘要 --- p.vii / Acknowledgement --- p.x / Table of Contents --- p.xi / List of Tables --- p.xvi / List of Figures --- p.xx / Abbreviations --- p.xxi / Publications and Conference Presentation --- p.xxiv / Awards Received --- p.xxvii / Chapter Chapter 1 --- General Introduction --- p.1 / Chapter 1.1 --- Uveitis-one of the most challenging dilemmas in ophthalmology --- p.1 / Chapter 1.1.1 --- Classification of uveitis --- p.4 / Chapter 1.1.2 --- Clinical characteristics of uveitis --- p.5 / Chapter 1.1.3 --- Epidemiology of uveitis --- p.6 / Chapter 1.1.4 --- Etiology of uveitis --- p.9 / Chapter 1.1.5 --- Current management of uveitis and future perspectives --- p.11 / Chapter 1.2 --- The Descriptive Complexity of Uveitis --- p.13 / Chapter 1.3 --- Uveitis Genetics Research Strategies --- p.14 / Chapter 1.3.1 --- Candidate gene association study --- p.14 / Chapter 1.3.2 --- The identification of new genes --- p.15 / Chapter 1.4 --- Statistical Genetics for Uveitis --- p.16 / Chapter 1.4.1 --- Hardy-Weinberg equilibrium test --- p.16 / Chapter 1.4.2 --- Univariate analysis --- p.16 / Chapter 1.4.3 --- Linkage disequilibrium --- p.17 / Chapter 1.4.4 --- Haplotype analysis --- p.18 / Chapter 1.4.5 --- Multivariable analysis --- p.19 / Chapter Chapter 2 --- Objectives --- p.21 / Chapter Chapter 3 --- General Materials and Methods --- p.23 / Chapter 3.1 --- Overall Study Design --- p.23 / Chapter 3.2 --- Research Ethics --- p.23 / Chapter 3.3 --- Study Subjects Recruitment --- p.23 / Chapter 3.4 --- Demographic and Clinical Characteristics of Patients --- p.24 / Chapter 3.4.1 --- Anterior uveitis (AU) --- p.24 / Chapter 3.4.2 --- Non-infectious intermediate and posterior uveitis (NIPU) --- p.25 / Chapter 3.5 --- General Methods --- p.26 / Chapter 3.5.1 --- Total genomic DNA extraction in study subjects --- p.26 / Chapter 3.5.2 --- Taqman SNP genotyping --- p.27 / Chapter 3.5.3 --- Nested polymerase chain reaction (nPCR) --- p.27 / Chapter 3.6 --- Statistical Analysis --- p.28 / Chapter 3.6.1 --- Hardy-Weinberg equilibrium test --- p.28 / Chapter 3.6.2 --- Individual SNP association analysis --- p.28 / Chapter 3.6.3 --- Pairwise linkage disequilibrium and haplotype analysis --- p.30 / Chapter 3.6.4 --- Genotype-phenotype correlation analysis --- p.31 / Chapter 3.6.5 --- Gene-gene interaction analysis --- p.31 / Chapter Chapter 4 --- Investigation into Genetic Determinants of Uveitis --- p.32 / Chapter 4.1 --- A Critical Review on The Roles of Genetic Factors in Uveitis --- p.32 / Chapter 4.1.1 --- Human leukocyte antigens (HLA) --- p.33 / Chapter 4.1.2 --- Interleukin (IL) genes --- p.36 / Chapter 4.1.3 --- Chemokine and chemokine receptor genes --- p.37 / Chapter 4.1.4 --- Tumor necrosis factor (TNF) genes --- p.39 / Chapter 4.1.5 --- Other genes implicated in susceptibility to uveitis --- p.40 / Chapter 4.1.6 --- Complement system --- p.42 / Chapter 4.1.7 --- Conclusions and directions --- p.43 / Chapter 4.2 --- Interleukin and CFH Polymorphisms in Uveitis --- p.49 / Chapter 4.2.1 --- Introduction --- p.49 / Chapter 4.2.2 --- Study subjects --- p.50 / Chapter 4.2.3 --- SNP selection and genotyping --- p.50 / Chapter 4.2.4 --- Statistical analysis --- p.51 / Chapter 4.2.5 --- Association of interleukin and CFH polymorphisms with AU --- p.51 / Chapter 4.2.5.1 --- Association between SNPs and AU --- p.51 / Chapter 4.2.5.2 --- Association between SNPs and AU stratified by gender --- p.52 / Chapter 4.2.5.3 --- Association between SNPs and AU stratified by HLA-B27 status --- p.52 / Chapter 4.2.5.4 --- Genotype-phenotype correlation analysis --- p.53 / Chapter 4.2.6 --- Association of interleukin and CFH polymorphisms with NIPU --- p.53 / Chapter 4.2.6.1 --- Association between SNPs and NIPU --- p.53 / Chapter 4.2.6.2 --- Association between SNPs and NIPU stratified by subtypes --- p.54 / Chapter 4.2.6.3 --- Association between SNPs and NIPU stratified by gender --- p.54 / Chapter 4.2.7 --- Discussion --- p.55 / Chapter 4.2.7.1 --- Association of interleukin and CFH polymorphisms with AU --- p.55 / Chapter 4.2.7.2 --- Association of interleukin and CFH polymorphisms with NIPU --- p.58 / Chapter 4.3 --- C2/CFB Polymorphisms in Uveitis --- p.70 / Chapter 4.3.1 --- Introduction --- p.70 / Chapter 4.3.2 --- Study subjects --- p.70 / Chapter 4.3.3 --- SNP selection and genotyping --- p.70 / Chapter 4.3.4 --- Statistical analysis --- p.71 / Chapter 4.3.5 --- Association of C2/CFB polymorphisms with AU --- p.71 / Chapter 4.3.5.1 --- Association between SNPs and AU --- p.71 / Chapter 4.3.5.2 --- Association between SNPs and AU stratified by HLA-B27 status --- p.72 / Chapter 4.3.5.3 --- Linkage disequilibrium and haplotype association analysis --- p.73 / Chapter 4.3.5.4 --- Genotype-phenotype correlation analysis --- p.73 / Chapter 4.3.5.5 --- Joint-effect analysis between CFH and CFB in AU --- p.73 / Chapter 4.3.6 --- Association of C2/CFB polymorphisms with NIPU --- p.74 / Chapter 4.3.6.1 --- Association between SNPs and NIPU --- p.74 / Chapter 4.3.6.2 --- Association between SNPs and NIPU stratified by subtypes --- p.74 / Chapter 4.3.6.3 --- Association between SNPs and NIPU stratified by gender --- p.75 / Chapter 4.3.6.4 --- Linkage disequilibrium and haplotype association analysis --- p.75 / Chapter 4.3.7 --- Discussion --- p.75 / Chapter 4.3.7.1 --- Association of C2/CFB polymorphisms with AU --- p.75 / Chapter 4.3.7.2 --- Association of C2/CFB polymorphisms with NIPU --- p.77 / Chapter 4.4 --- SERPING1 Gene Polymorphisms in Uveitis --- p.94 / Chapter 4.4.1 --- Introduction --- p.94 / Chapter 4.4.2 --- Study subjects --- p.94 / Chapter 4.4.3 --- SNP selection and genotyping --- p.95 / Chapter 4.4.4 --- Statistical analysis --- p.95 / Chapter 4.4.5 --- Association of SERPING1 polymorphisms with AU --- p.95 / Chapter 4.4.5.1 --- Association between SNPs and AU --- p.95 / Chapter 4.4.5.2 --- Association between SNPs and AU stratified by gender --- p.96 / Chapter 4.4.5.3 --- Association between SNPs and AU stratified by HLA-B27 status --- p.96 / Chapter 4.4.5.4 --- Association between SNPs and AU stratified by clinical features --- p.96 / Chapter 4.4.6 --- Association of SERPING1 polymorphisms with NIPU --- p.96 / Chapter 4.4.6.1 --- Association between SNPs and NIPU --- p.97 / Chapter 4.4.6.2 --- Association between SNPs and NIPU stratified by subtypes --- p.97 / Chapter 4.4.6.3 --- Association between SNPs and NIPU stratified by gender --- p.97 / Chapter 4.4.7 --- Discussion --- p.98 / Chapter 4.5 --- C3 Gene Polymorphisms in Uveitis --- p.109 / Chapter 4.5.1 --- Introduction --- p.109 / Chapter 4.5.2 --- Study subjects --- p.109 / Chapter 4.5.3 --- SNP selection and genotyping --- p.110 / Chapter 4.5.4 --- Statistical analysis --- p.110 / Chapter 4.5.5 --- Association of C3 polymorphisms with AU --- p.110 / Chapter 4.5.5.1 --- Association between SNPs and AU --- p.110 / Chapter 4.5.5.2 --- Association between SNPs and AU stratified by gender --- p.111 / Chapter 4.5.5.3 --- Association between SNPs and AU stratified by HLA-B27 status --- p.111 / Chapter 4.5.5.4 --- Association between SNPs and AU stratified by clinical features --- p.111 / Chapter 4.5.6 --- Association of C3 polymorphisms with NIPU --- p.111 / Chapter 4.5.6.1 --- Association between SNPs and NIPU --- p.111 / Chapter 4.5.6.2 --- Association between SNPs and NIPU stratified by subtypes and gender --- p.112 / Chapter 4.5.7 --- Discussion --- p.112 / Chapter 4.6 --- C5 Gene Polymorphisms in Uveitis --- p.126 / Chapter 4.6.1 --- Introduction --- p.126 / Chapter 4.6.2 --- Study subjects --- p.126 / Chapter 4.6.3 --- SNP selection and genotyping --- p.127 / Chapter 4.6.4 --- Statistical analysis --- p.127 / Chapter 4.6.5 --- Association of C5 polymorphisms with AU --- p.127 / Chapter 4.6.5.1 --- Association between SNPs and AU --- p.127 / Chapter 4.6.5.2 --- Association between SNPs and AU stratified by gender --- p.128 / Chapter 4.6.5.3 --- Association between SNPs and AU stratified by HLA-B27 status and clinical features --- p.128 / Chapter 4.6.6 --- Association of C5 polymorphisms with NIPU --- p.128 / Chapter 4.6.6.1 --- Association between SNPs and NIPU --- p.128 / Chapter 4.6.6.2 --- Association between SNPs and NIPU stratified by subtypes --- p.129 / Chapter 4.6.6.3 --- Association between SNPs and NIPU stratified by gender --- p.129 / Chapter 4.6.7 --- Discussion --- p.129 / Chapter Chapter 5 --- Conclusions and Future Perspectives --- p.143 / Chapter 5.1 --- General Conclusion --- p.143 / Chapter 5.2 --- Future Research in Uveitis Molecular Genetics --- p.144 / REFERENCES --- p.148

Using bioinformatics we have identified stm3071 as a possible regulator of anaerobically induced genes involved in metal homeostasis (Price-Carter et al., 2001) and the aim of this study is to determine the function of stm3071 and define the conditions that induce its expression. Cobalt is required for incorporation into cobalamin (vitamin B12) which is important during S. Typhimurium infection. Vitamin B12 is synthesised de novo under anaerobic conditions and is required for metabolism of 1,2-propanediol and ethanolamine which act as sources of carbon and nitrogen when Salmonella is in the gut (Raux et al., 1996; Thiennimitr et al., 2011). Therefore, sensing Co2+ from the environment, and maintaining Co2+ homeostasis, to avoid metal-mediated toxicity, is required for vitamin B12 biosynthesis. Using λ-red based mutagenesis we have constructed a deletion mutant in order to investigate the function of stm3071. We examined the effect of mutation on the utilisation of 1,2-propanediol under anaerobic conditions and ability to produce vitamin B12. We have also tested the effect of mutation on tolerance to cobalt both aerobically and anaerobically. In order to monitor conditions in which Pstm3071 is switched on, a Pstm3071::lacZ transcriptional fusion was constructed in plasmid pRS415. Levels of β-galactosidase activity were measured in the presence of cobalt in both Δstm3071 and SL1344 (wild type strain) under anaerobic conditions. Anaerobic growth experiments and B12 assays showed that stm3071 is not essential for growth or synthesis of vitamin B12. In addition, cobalt tolerance in both aerobic and anaerobic conditions was unaffected. However, as measured by β-galactosidase assay, our data suggests that Pstm3071 expression is induced in the presence of cobalt in the deletion mutant. In contrast, we observed no difference in expression of Pstm3071 in the presence or absence of cobalt in SL1344.

Submitted by Fabíola Silva (fabiola.silva@famerp.br) on 2017-03-01T19:46:36Z No. of bitstreams: 1 rogeriodelarco_dissert.pdf: 1300532 bytes, checksum: 8f79b58857fc2ea4ac77633ad6fd6445 (MD5) / Made available in DSpace on 2017-03-01T19:46:36Z (GMT). No. of bitstreams: 1 rogeriodelarco_dissert.pdf: 1300532 bytes, checksum: 8f79b58857fc2ea4ac77633ad6fd6445 (MD5) Previous issue date: 2014-08-21 / Introduction. Chronic pain in leprosy plays an important role for being responsible for the physical and psychological suffering that produces. Objectives: To identify the difficulties in diagnosing and treating neuropathic pain caused by Leprosy, as well as to investigate the main determinants of neuropathic pain. Methods: Eighty-five patients who completed treatment for leprosy with MDT/WHO were evaluated for neuropathic pain using the Douleur Neuropathic 4 test (DN4). A detailed questionnaire and neurological examination were employed to complement the results. Results: Forty-eight patients were excluded because they did not have pain at the time of this study. Of the 37 patients with pain, 22 (59.5%) reported neuropathic or mixed pain and 70.8% characterized their pain as moderate or severe; 81.8% had suffered with pain for more than 6 months. Only 12 (54.5%) patients had been diagnosed with the symptom and so the problem had not been identified in almost half of the cases (10; 45.5%). Of the 12 patients on medications for neuropathic pain, only 5 (41.6%) stated that it had improved with the pain of the other 7 patients (58.4%) remaining the same or getting worse. The difference in the improvement of pain between treated (n = 12) and untreated patients (n = 10) was significant (p-value = 0.020). Conclusion: Neuropathic pain is an important cause of suffering for patients with leprosy and is still neglected by the medical team because of difficulties to diagnose it. The appropriate recognition and treatment of this condition may relieve symptoms and improve the quality of life of patients. / Introdução: A dor crônica em hanseníase tem um papel importante por ser responsável pelo sofrimento físico e psicológico que produz. Objetivos: Avaliar a presença e as características de dor neuropática nas pessoas que tiveram hanseníase. Casuística e métodos: Oitenta e cinco (n=85) pacientes que completaram tratamento para hanseníase com PQT/OMS foram avaliados para dor neuropática por meio do teste Douleur Neuropathic 4 (DN4). Criterioso questionário e exame neurológico foram aplicados para complementar os dados. Resultados: Quarenta e oito pacientes foram excluídos por não apresentarem dor ou por se referirem a ela apenas no passado. Dos 37 pacientes com dor confirmou-se que 22 (59,5%) tinham dor neuropática ou mista e destes, 70,8% caracterizavam esta dor como de intensidade moderada ou grave, sendo que 81,8% sofriam por um período maior que 6 meses. Apenas 12 (54,5%) pacientes haviam sido diagnosticados com o problema e quase metade dos casos – 10 (45,5%) ainda estavam sem reconhecimento. Quanto ao tratamento medicamentoso (n=12) para a dor neuropática, apenas 5 (41,6%) responderam que tiveram melhora, os outros 7 (58,4%) ficaram igual ou pioraram comparado ao quadro inicial. A análise estatística comparando a melhora da dor entre os tratados – 12 pacientes, e os não tratados – 10 pacientes é significante (valor de p = 0,020). Conclusão: A dor neuropática é causa importante de sofrimento no paciente com hanseníase e mesmo assim é negligenciada pela equipe médica que tem dificuldade em diagnosticá-la. O adequado reconhecimento e tratamento desta condição podem aliviar sintomas e melhorar a qualidade de vida destes pacientes.

A epidemia de HIV/AIDS, que sofreu grandes mudanças em seus padrões clínicos e epidemiológicos, atingiu neste século sua estabilidade. Durante estes 30 anos os profissionais de saúde aprenderam muito sobre a doença e hoje esse aprendizado reflete-se em maior eficiência no diagnóstico e no tratamento da infecção pelo vírus e de suas manifestações oportunistas. As lesões orais associadas ao HIV são motivo de estudo desde os primeiros relatos da doença no início dos anos 80, e foram relacionadas ao sexo, idade, naturalidade, forma de exposição ao vírus e a padrões virológicos e imunológicos. Mas a pressão exercida pelas mudanças das características demográficas da epidemia sobre as manifestações bucais oportunistas do HIV não foi levada em consideração. A estabilidade da epidemia e o amadurecimento do conhecimento proporcionam um terreno propício para a avaliação da real prevalência dessas manifestações. Esta pesquisa tem como objetivo verificar como está este panorama no Brasil. Cento e quatro pacientes HIV+ em início de TARV foram avaliados clinicamente, e foram colhidos dados demográficos e exames laboratoriais, além da execução de sialometria e índice CPO-D. A população avaliada foi predominantemente masculina (78,8%) com média de 37,8 anos de idade. A via de transmissão do HIV foi sexual, sendo 57,7% através do sexo homo/bissexual e 38,4% com sexo heterossexual. 52,9 % souberam de sua soropositividade a menos de um ano. O CD4 médio foi de 223 céls/mm³ e a CV de 121.400 cópias/ml. As lesões extraorais foram diagnosticadas em 10,6% dos pacientes, sendo as hiperpigmentações de pele e mucosa (9,6%) e o aumento de glândulas salivares (0,96%) as lesões mais encontradas. A candidíase oral (49%) e a leucoplasia pilosa (41,3%) foram as lesões intraorais mais prevalentes. A xerostomia foi queixa de 46,6% e a hipossalivação foi diagnosticada em 18% e 48% dos pacientes, dependendo da metodologia utilizada para avaliação. O índice CPOD foi de 14,4, considerado alto pela OMS. A presença de lesões orais, candidíase e leucoplasia pilosa foram associadas à baixa imunidade e a presença de lesões orais e candidíase a cargas virais altas. A hipossalivação, avaliada através do fluxo salivar estimulado e representando principalmente a saliva da parótida, foi relacionado com níveis de CD8 alterados. Comparado com a literatura revisada, a prevalência de lesões orais associadas ao HIV apresenta-se alterada neste estudo, principalmente pela ausência de diagnóstico de neoplasias malignas e baixa prevalência de outras lesões orais associadas à aids. / HIV/AIDS epidemic, which has undergone major changes in their clinical and epidemiological patterns, in this century reached its stability. During these 30 years, much has been learned about the disease by health care professionals and nowadays, all this knowledge is reflected in greater efficiency in the diagnosis and treatment of virus infection and its opportunistic manifestations. HIV oral related lesions have been studied since the first reports of the disease in the earlies 80\'s, and were related to gender, age, place of birth, route of virus exposure, and virological and imunological patterns. Demographic changes of the disease over oral HIV opportunistic diseases have not been taken into consideration. The stability of epidemics and maturing of knowledge provide a fertile ground for the evaluation of the real prevalence of these manifestations. This research aims to verify this scenario in Brazil. A hundred and four HIV+ patients starting HAART were evaluated clinically, and demographic data and laboratory tests were collected, in addition to performing sialometry and DMFT index. The population was predominantly male (78,8%), average of 37,8 years old. The route of HIV transmission was sexual, 57,7% through homo/bisexual sex, and heterosexual sex, with 38,4%. 52,9% knew their HIV sero status to less than one year. The average CD4 was 223 cell/mm3 and CV of 121,400 copies/ml. Extra oral lesions were observed in 10,6% of patients, the skin and mucosal hyperpigmentation (9,6%) and enlargement of salivary glands (0,96%) were the lesions diagnosed. Oral candidiasis (49%) and oral hairy leukoplakia (41,3%) were the most prevalent intraoral lesions. Xerostomia was a complaining of 46,6% and hyposalivation was diagnosed in 18% and 48% of patients, depending on the methodology applied. The DMFT index was 14,4, considered high by WHO. Oral lesions, oral candidiasis and oral hairy leukoplakia were associated to low immunity and high viral load levels. Hyposalivation, evaluated by stimulated salivary flow (mainly, representing the saliva produced by parotid gland) was associated with altered levels of CD8. Compared to reviewed literature, oral lesions prevalence was considered altered in this research, notably the lack of diagnosis of malignant neoplasias and low prevalence of other lesions associated with aids. .