Creutzfeldt-Jakob disease (CJD) is the commonest form of human prion disease and occurs in sporadic, genetic and acquired forms. The causative agents (prions) appear to be composed entirely of a modified host protein, the prion protein, which undergoes misfolding to a disease-associated isoform closely associated with infectivity that is resistant to conventional methods of decontamination. Prions can be transmitted from one individual to another by medical and surgical procedures, resulting in iatrogenic CJD (iCJD). The commonest cause of iCJD is the inoculation of cadaveric pituitary-derived human growth hormone (hGH) to treat growth hormone deficiency in children; this form of treatment was abandoned in 1985 after the first UK case of iCJD in a hGH recipient was identified. Seventy-eight cases of iCJD have since occurred in the UK cohort of 1849 hGH recipients, including a case in 2016. This thesis describes a comprehensive tissue-based and molecular genetic analysis of the largest series (35 cases) of UK hGH-iCJD cases reported to date, including in vitro kinetic molecular modelling of genotypic factors influencing prion transmission. The results show that the polymorphism at codon 129 of the prion protein gene strongly influences the disease incubation period in hGH-iCJD (from 7.8-32.3 years in this series) and interacts with the infectious prion strain to govern the molecular and pathological characteristics of iCJD. The findings are consistent with the hypothesis that the UK hGH-iCJD epidemic resulted from transmission of the V2 human prion strain, which is found in the second most common form of sporadic CJD. The investigation also found accumulation of the amyloid beta (Aβ) protein associated with Alzheimer’s disease (AD) in the brains and cerebral blood vessels in 18/35 hGH-iCJD patients and 5/12 control patients who had been treated with hGH, but died from causes other than iCJD. In contrast, Aβ accumulation was markedly less prevalent in age-matched patients who died from sporadic CJD (1/15 cases) and variant CJD (2/33 cases). These results are consistent with the hypothesis that Aβ, which can accumulate in the pituitary gland, was present in the inoculated hGH preparations and seeded into the brains of around 50% of all hGH recipients, producing AD-like neuropathology and cerebral amyloid angiopathy (CAA). This provides further evidence of the prion-like properties of Aβ and gives insight into the potential for possible transmission of AD/CAA. It is uncertain whether any Aβ seeding within the brains of surviving patients in the UK hGH recipient cohort will ultimately result in clinical AD; however, the CAA in these patients may be complicated by intracerebral haemorrhage resulting from rupture of the blood vessels damaged by Aβ accumulation within their walls.

Este trabalho aborda o tema do potencial iatrogênico da psicanálise. Desde a Grécia Antiga, com Hipócrates, estabeleceu-se como princípio basilar das práticas de cura a necessidade de que, antes de tudo, não se deve causar mal ao paciente. Sabe-se que qualquer tratamento com potencial para curar um paciente tem também potencial de produzir efeitos iatrogênicos. Contudo, no campo da saúde mental, a pesquisa sobre o tema ainda pouco avançou, enfrentando resistência por parte dos profissionais e também obstáculos metodológicos, em particular, a falta de terminologia adequada para identificar, classificar e analisar os efeitos iatrogênicos. Pesquisas sobre o tema mostram que tratamentos em saúde mental provocam piora do quadro clínico do paciente em até 10% dos casos. Indicam também a importância da relação entre paciente e terapeuta, enquanto fonte de eficácia do tratamento, mas também fonte de produção de efeitos iatrogênicos. O presente trabalho é uma pesquisa teórica, que por meio de uma revisão sistemática da literatura sobre o tema do potencial iatrogênico da Psicanálise, visa investigar em que condições o psicanalista e/ou o tratamento psicanalítico podem produzir efeitos iatrogênicos e de que modo a formação psicanalítica pode contribuir para redução desses efeitos. Espera-se que a pesquisa sirva de base para o desenvolvimento de um esquema teórico conceitual que amplie a discussão sobre o tema do potencial iatrogênico da psicanálise. Até o momento foi possível elaborar a proposta de terminologia aplicável ao campo das iatrogenias, a partir da diferenciação entre iatrogenias dolosas e culposas, e com uso das categorias como: imperícia, negligencia e imprudência. Abordamos também a questão dos diversos usos feitos do poder no curso do tratamento, articulado ao tema da responsabilidade do psicanalista, a partir da proposta de formalização da práxis psicanalítica à semelhança de um jogo composto por três elementos - o sujeito, o saber e o sexo, tal como proposto por Jacques 11 Lacan no Seminário XII. Concluímos que nas tentativas de simplificação, redução, recortes ou amputações da prática e da teoria psicanalítica é que residem os maiores riscos de aumento no potencial iatrogênico do tratamento. Espera-se que a presente pesquisa contribua de modo relevante para a construção de um esquema teórico conceitual que amplie a discussão sobre o tema da iatrogenia dos tratamentos em saúde mental, visando, em última instancia, compreender as possibilidades de redução de danos decorrentes do tratamento psicanalítico / This paper discusses the iatrogenic potential of psychoanalysis. Since ancient Greece, with Hippocrates, it was established as a basic principle of healing practices that, first of all, the doctor shall not cause harm to the patient. Today, it is known that any potential treatment for curing a patient also has the potential of producing iatrogenic effects. However, in the field of mental health, research on the subject has made little progress, facing resistance from professionals and methodological obstacles, particularly the lack of a proper terminology to identify, classify and analyze the iatrogenic effects. Research on the subject shows that mental health treatments may cause worsening of the clinical condition of the patient in up to 10% of cases. Researches also indicate the importance of the relationship between patient and therapist, as a source of treatment efficacy, but also as the source of iatrogenic effects. This work is a theoretical research that through a systematic review of the literature on the iatrogenic potential of psychoanalysis, aims to investigate under what conditions the analyst and/or psychoanalytic treatment may produce iatrogenic effects and how psychoanalytic training can help reduce these effects. It is hoped that this research will serve as a basis for the development of a conceptual theoretical framework to broaden the discussion on the subject of the iatrogenic potential of psychoanalysis. So far it was possible to develop a proposal of terminology applicable to the field of iatrogenic effects in mental health, based on the distinction between intentional and culpable iatrogenic, and use of categories such as malpractice, negligence and recklessness. This research also addressed the issue of the different uses made of power in the course of treatment, linked to the psychoanalysts responsibility when conducting a treatment, based on the proposed formalization of psychoanalytic practice like a game, revolving around three elements - the subject, knowledge and sex - as proposed by Jacques Lacan, in Seminar XII. We conclude to argue that in the attempts of simplification, reduction, cuts or amputations of psychoanalytical practice and theory resides the greatest increases in iatrogenic potential of psychoanalysis. It is hoped that this research will 13 contribute in a relevant way for the construction of a conceptual theoretical framework to broaden the discussion on the subject of iatrogenic treatments in mental health, aimed at ultimately, understand the harm reduction opportunities arising from psychoanalytical treatment

Orientador: Elinton Adami Chaim / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T00:49:38Z (GMT). No. of bitstreams: 1 Machado_RicardoRossetto_M.pdf: 1957576 bytes, checksum: 8139974c79a4445e5f71c069dd543c8a (MD5) Previous issue date: 2014 / Resumo: Contexto: As lesões iatrogênicas da via biliar são de difícil manejo e requerem equipes com experiência para a reconstrução da via biliar. O objetivo desse estudo foi avaliar tardiamente os 21 anos de experiência em um centro de referência terciário das reconstruções bileodigestivas após a lesão iatrogênica da via biliar pós-colecistectomia e os fatores envolvidos na estenose da anastomose bileodigestiva. Métodos: Análise retrospectiva de 91 pacientes submetidos a hepaticojejunostomia em Y de Roux entre 1993 e 2013. Dados pré-operatórios, sintomas clínicos após a lesão, reoperações, classificação da lesão e evolução ambulatorial foram avaliados. O teste de qui-quadrado e a regressão logística foram usados para determinar os fatores envolvidos na estenose da anastomose bileodigestiva. Resultados: Mulheres eram 84,5% dos pacientes, média de idade de 43 anos. Foi observada associação entre fístula biliar e derivação bileodigestiva no serviço de origem (p=0,009). Colangite e sintomas clínicos no seguimento ambulatorial foram associadas com a classificação de Bismuth (p=0,008 e p<0,001). O aumento em uma unidade na aspartato aminotransferase em 12 meses de pós-operatório, aumentou a chance de apresentar sintomas clínicos no ambulatório em 4,8% (IC 95%=1,003-1,096). A derivação bileodigestiva no serviço de origem aumentou a chance de associação com fístula biliar em 5,9 vezes (IC 95%=1,132-31,142). Conclusão: A reconstrução da via biliar após a lesão iatrogênica no tratamento cirúrgico da colecistectomia deve ser realizado por cirurgiões experientes e, de preferência, em centros de referência terciário / Abstract: Background: Iatrogenic bile duct injuries are difficult to manage and require surgical teams with experience in bile duct repair. The aim of the study was to describe and correlate factors associated with biliary-enteric anastomosis stricture in a tertiary referral center. Methods: A retrospective analysis of 91 patients undergoing Roux-en-Y hepaticojejunostomy from 1993 to 2013 was carried out. Preoperative data, symptoms following injury, reoperations, classification of lesions and outpatient outcome were evaluated. The chi-square test and logistic regression were used to determine factors involved in biliary-enteric anastomosis stricture. Results: Women comprised 84.5% of patients (mean age: 43 years). An association between bile leakage and biliary-enteric anastomosis at the original health care facility (p=0.009) was observed. Cholangitis and symptoms in the outpatient facility were associated with Bismuth classification (p=0.008 and p<0.001). For each additional unit increase in aspartate aminotransferase values in the 12-month postoperative period, the likelihood of outpatient symptoms increased by 4.8% (95% CI=1.003-1.096). A biliary-enteric anastomosis performed at the original health care facility increased 5.9-fold the chance that a bile leakage was associated (95% CI=1.132-31.142). Conclusion: Bile duct reconstruction due to iatrogenic injury is challenging. To achieve success, repair must be performed by experienced surgeons in tertiary referral centers / Mestrado / Fisiopatologia Cirúrgica / Mestre em Ciências

La prise en charge d’un patient atteint d’un cancer impose, au soignant, la recherche du meilleur traitement antinéoplastique possible en association avec un engagement d’accompagnement depuis l’annonce du diagnostic jusqu’à la phase après cancer ou le décès. Au cours de son parcours de soin, le malade et ses proches vont être confrontés à différentes équipes, différentes visions du traitement et différentes approches du soin. Le travail présenté consiste en une analyse nationale française sur l’organisation des soins d’accompagement ainsi que la gestion de la iatrogénie liée à trois grandes familles de thérapeutiques symptomatiques : les érythropoïétines, les biphosphonates et les morphiniques. Basé sur cette photographie du soin d’accompagnement en cancérologie, le développement de ces soins sur un établissement sera alors présenté depuis la gestion ambulatoire en hospitalisation de jour, jusqu’à l’hospitalisation complète dans une unité pilote. Le lien, les différences et les complémentarités entre les équipes aux phases curatives et palliatives seront alors discutés, permettant de définir la place et l’importance du regard global et réunificateur par le biais des soins de support en cancérologie / The management of a cancer patient requires, to the caregivers, finding the best antineoplastic therapy in combination with support involvement from the diagnosis to the stage after cancer or death. During the course of care, patient and family will be confronted with different teams, different visions and different treatment approaches of their care. The work presented starts threw an analysis of French organizations of supportive care and management of iatrogenic effects due to three main types of symptomatic therapeutics: erythropoietins, bisphosphonates and opioids. Based on this photograph of accompanying cancer care, the development in an institution of an health care will be presented for ambulatory management of day hospital for chemotherapy administration, until full hospitalization in a pilot unit. The link, the differences and complementaries between the teams in curative and palliative phases will be discussed to define the role and importance of the overall look and unifying supportive care in oncology

Iatrogenic tracheal ruptures are rare but severe complications of medical interventions. The main goal of this study was to explore prognostic factors for all-cause mortality and rupture-related (adjusted) mortality. We retrospectively analyzed patients admitted to an academic referral center over a 15-year period (2004–2018). Fifty-four patients met the inclusion criteria, of whom 36 patients underwent surgical repair and 18 patients were treated conservatively. In a 90-day follow-up, the all-cause mortality was 50%, while the adjusted mortality was 13%. Rupture length was identified as a predictor for all-cause mortality (area under the curve, 0.84; 95% confidence interval (CI) 0.74–0.94) with a cutoff rupture length of 4.5 cm (sensitivity, 0.70; specificity, 0.81). Multivariate analysis confirmed rupture length as a prognostic factor for all-cause mortality (adjusted hazard ratio (HR) 1.5; 95% CI 1.2–1.9; p = 0.001), but not for adjusted mortality (HR 1.5; 95% CI 0.97–2.3; p = 0.068), while mediastinitis predicted adjusted mortality (HR 5.8; 95% CI 1.1–31.7; p = 0.042), but not all-cause mortality (HR 1.6; 95% CI 0.7–3.5; p = 0.243). The extent of iatrogenic tracheal rupture and mediastinitis might be relevant prognostic factors for all-cause mortality and adjusted mortality, respectively.

Introdução: idosos hospitalizados apresentam maior risco de sofrer eventos adversos na internação que adultos jovens, com consequências mórbidas significativas. O objetivo deste estudo é estimar prospectivamente a freqüência de eventos adversos médicos, os fatores de risco para sua ocorrência e sua relação com óbito intrahospitalar em idosos admitidos aos leitos destinados a cuidados de descompensações clínicas agudas de uma enfermaria de geriatria. Métodos: estudo de coorte prospectivo incluindo as admissões de pacientes com 60 anos ou mais aos leitos destinados a cuidados de descompensações clínicas agudas da Enfermaria de Geriatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, com duração maior de 24 horas, entre abril de 2007 e julho de 2008. Na admissão foram obtidos dados sobre sexo, idade, número de drogas utilizadas, presença de síndromes geriátricas (imobilidade, instabilidade postural, incontinência esfincteriana, demência, depressão e delirium), comorbidades, status funcional (índice de Katz) e gravidade de doença (SAPS II). Durante o período de internação avaliou-se a ocorrência de delirium, infecção, a prescrição de medicamentos inapropriados ao idoso (critérios de Beers) e óbito intrahospitalar. Um observador não envolvido nos cuidados dos pacientes relatou a ocorrência de eventos adversos médicos. Resultados: foram incluídas 171 admissões de pacientes, com idade média de 78,12 anos ± 9,27, sendo 101 do sexo feminino. Ocorreram 187 eventos adversos médicos em 94 admissões (55%), com 2,01 eventos por admissão. Não foi possível identificar fatores preditores da ocorrência de eventos adversos médicos. As admissões com ocorrência de eventos adversos apresentaram maior tempo de internação na enfermaria de geriatria (21,41 dias ± 15,08 X 10,91 dias ± 7,21, p<0,001) e maior mortalidade intra-hospitalar que as admissões onde não houve eventos. Como fatores preditores de mortalidade intra-hospitalar após análise multivariada identificou-se o SAPS II (Razão de chances (OR)=1,13, intervalo de confiança (IC) 95% 1,07-1,20, p<0,001), índice de Katz na admissão (OR=1,47, IC 95% 1,18-1,83, p=0,001) e ocorrência de eventos adverso médico (OR=3,59, IC 95% 1,55-8,30, p=0,003). Conclusões: Eventos adversos médicos devem ser considerados em todo idoso hospitalizado uma vez que são bastante frequentes nessa população. Não há um perfil de risco para indivíduos suscetíveis. Estes eventos apresentam impacto na mortalidade e no tempo de internação. / Introduction: hospitalized seniors are at higher risk of adverse events than young adults and it is a morbid condition. The aim of this study is to prospectively estimate the frequency of medical adverse events in elderly patients admitted to an acute care geriatric ward, the predictive factors to its occurrence, and their implication in death during hospitalization. Methods: prospective cohort study including the admissions of elderly patients that lasted more than 24 hours to the acute care session of the geriatric ward in Hospital das Clínicas of Faculdade de Medicina, Universidade de São Paulo, between 2007 and 2008. At admission the variables assessed were age, gender, number of drugs, geriatric syndromes (immobility, postural instability, dementia, depression, delirium and incontinency), comorbidities, functional status (Katz Score), and severity of illness (SAPS II). During hospitalization, the occurrence of delirium, infection, the prescription of potentially inappropriate medications according to Beers criteria and death were assessed. An observer not involved in the patients care reported the medical adverse events. Results: 171 admissions were enrolled in the study, mean age 78.12 ± 9.27 years, 101 females. 187 medical adverse events occurred in 94 admissions (55%), with 2.01 events per admission. Predictors to medical adverse events were not found. Time of hospitalization (21.41 days ± 15.08 X 10.91 days ± 7.21, p<0.001) and mortality (39 (41.5%) X 17 (22.1%), p=0.007) were respectively longer and higher in the admissions with medical adverse events. Death was independently predicted by SAPS II (Odds-ratio (OR)=1.13, Confidence interval (CI) 95% 1.07-1.20, p<0.001), Katz score (OR=1.47, CI 95% 1.18-1.83, p=0.001), and medical adverse events (OR=3.59, CI 95% 1.55-8.30, p=0.003). Conclusion: Medical adverse events shall be sought in every hospitalized older adult since there is not a risk profile of susceptible patients, and its burden is high, leading to death and longer hospital stays.

Introdução: idosos hospitalizados apresentam maior risco de sofrer eventos adversos na internação que adultos jovens, com consequências mórbidas significativas. O objetivo deste estudo é estimar prospectivamente a freqüência de eventos adversos médicos, os fatores de risco para sua ocorrência e sua relação com óbito intrahospitalar em idosos admitidos aos leitos destinados a cuidados de descompensações clínicas agudas de uma enfermaria de geriatria. Métodos: estudo de coorte prospectivo incluindo as admissões de pacientes com 60 anos ou mais aos leitos destinados a cuidados de descompensações clínicas agudas da Enfermaria de Geriatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, com duração maior de 24 horas, entre abril de 2007 e julho de 2008. Na admissão foram obtidos dados sobre sexo, idade, número de drogas utilizadas, presença de síndromes geriátricas (imobilidade, instabilidade postural, incontinência esfincteriana, demência, depressão e delirium), comorbidades, status funcional (índice de Katz) e gravidade de doença (SAPS II). Durante o período de internação avaliou-se a ocorrência de delirium, infecção, a prescrição de medicamentos inapropriados ao idoso (critérios de Beers) e óbito intrahospitalar. Um observador não envolvido nos cuidados dos pacientes relatou a ocorrência de eventos adversos médicos. Resultados: foram incluídas 171 admissões de pacientes, com idade média de 78,12 anos ± 9,27, sendo 101 do sexo feminino. Ocorreram 187 eventos adversos médicos em 94 admissões (55%), com 2,01 eventos por admissão. Não foi possível identificar fatores preditores da ocorrência de eventos adversos médicos. As admissões com ocorrência de eventos adversos apresentaram maior tempo de internação na enfermaria de geriatria (21,41 dias ± 15,08 X 10,91 dias ± 7,21, p<0,001) e maior mortalidade intra-hospitalar que as admissões onde não houve eventos. Como fatores preditores de mortalidade intra-hospitalar após análise multivariada identificou-se o SAPS II (Razão de chances (OR)=1,13, intervalo de confiança (IC) 95% 1,07-1,20, p<0,001), índice de Katz na admissão (OR=1,47, IC 95% 1,18-1,83, p=0,001) e ocorrência de eventos adverso médico (OR=3,59, IC 95% 1,55-8,30, p=0,003). Conclusões: Eventos adversos médicos devem ser considerados em todo idoso hospitalizado uma vez que são bastante frequentes nessa população. Não há um perfil de risco para indivíduos suscetíveis. Estes eventos apresentam impacto na mortalidade e no tempo de internação. / Introduction: hospitalized seniors are at higher risk of adverse events than young adults and it is a morbid condition. The aim of this study is to prospectively estimate the frequency of medical adverse events in elderly patients admitted to an acute care geriatric ward, the predictive factors to its occurrence, and their implication in death during hospitalization. Methods: prospective cohort study including the admissions of elderly patients that lasted more than 24 hours to the acute care session of the geriatric ward in Hospital das Clínicas of Faculdade de Medicina, Universidade de São Paulo, between 2007 and 2008. At admission the variables assessed were age, gender, number of drugs, geriatric syndromes (immobility, postural instability, dementia, depression, delirium and incontinency), comorbidities, functional status (Katz Score), and severity of illness (SAPS II). During hospitalization, the occurrence of delirium, infection, the prescription of potentially inappropriate medications according to Beers criteria and death were assessed. An observer not involved in the patients care reported the medical adverse events. Results: 171 admissions were enrolled in the study, mean age 78.12 ± 9.27 years, 101 females. 187 medical adverse events occurred in 94 admissions (55%), with 2.01 events per admission. Predictors to medical adverse events were not found. Time of hospitalization (21.41 days ± 15.08 X 10.91 days ± 7.21, p<0.001) and mortality (39 (41.5%) X 17 (22.1%), p=0.007) were respectively longer and higher in the admissions with medical adverse events. Death was independently predicted by SAPS II (Odds-ratio (OR)=1.13, Confidence interval (CI) 95% 1.07-1.20, p<0.001), Katz score (OR=1.47, CI 95% 1.18-1.83, p=0.001), and medical adverse events (OR=3.59, CI 95% 1.55-8.30, p=0.003). Conclusion: Medical adverse events shall be sought in every hospitalized older adult since there is not a risk profile of susceptible patients, and its burden is high, leading to death and longer hospital stays.

Made available in DSpace on 2016-04-28T20:18:27Z (GMT). No. of bitstreams: 1 2006-Rafael de Oliveira Reis.pdf: 414371 bytes, checksum: cba37c20457ed19393a6150f550081e4 (MD5) Previous issue date: 2006-02-23 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / The thyroid diseases have been showed even more frequently in veterinary medicine, mainly hypothyroidism. There aren t many studies in Brazil about clinical changes of iatrogenic hypothyroidism in dogs. Thus, new studies must be done about this endocrine disturb. The aim of this study was to identify the main clinical-pathological changes in iatrogenic methimazole-induced hypothyroidism in dogs. We used five adult mongrel dogs, submitted to methimazole (0.5 mg.kg-1) chronic oral treatment by 120 days. We collected blood samples to evaluate the serum levels of Total T4, Free T4 and canine TSH. In the same days of the collect of blood samples, we made skin biopsy to histopathology study. All samples were collected in the days 0, 60 and 120. (It was also evaluated the serum levels of cholesterol and triglycerides.) We even evaluated cholesterol and triglycerides serum levels. It was evidenced an increase in cholesterol and triglycerides levels. The Total T4 levels kept unchanged. Therefore, the Free T4 levels showed a decrease after the 120 days of treatment. Moreover, the TSH levels increased after the firsts 60 days. Our results show that pharmacological induction of hypothyroidism in dogs can be carried out by methimazole. New studies should be done using this experimental paradigm to determinate the appropriated dose of methimazole in dogs in order to induce more expressive clinical manifestations. / Os dist?rbios da tire?ide em c?es t?m se apresentado cada vez mais freq?entes na rotina cl?nica veterin?ria, principalmente no que se refere ao hipotireoidismo. Considerando a necessidade de estudar particularidades referentes ?s altera??es cl?nicas do hipotireoidismo induzido iatrogenicamente em c?es, novos e mais aprofundados estudos sobre este dist?rbio devem ser feitos. O principal objetivo deste trabalho foi identificar as principais altera??es cl?nicas em c?es com hipotireoidismo iatrog?nico induzido por metimazol. Foram utilizados cinco c?es, machos, adultos, sem ra?a definida que foram submetidos a um tratamento oral cr?nico com metimazol na dose de 0,5mg.kg-1 durante 120 dias. Foram coletadas amostras sangu?neas para dosagens dos n?veis s?ricos de T4 total, T4 livre e TSH canino. Nos mesmos dias das coletas realizaram-se bi?psias cut?neas com o objetivo de obterem-se amostras para an?lise histopatol?gica. As amostras foram coletadas nos dias 0, 60 e 120. Avaliaram-se tamb?m os n?veis de colesterol e de triglicer?deos que apresentaram aumento signinficativo. A concentra??o de T4 total observada n?o apresentou queda significativa, ao contr?rio dos n?veis de T4 livre medidos por di?lise que diminuiram ap?s os 120 dias de tratamento, enquanto que os n?veis de TSH elevaram-se j? a partir da segunda amostra (no dia 60). Nossos resultados demonstram que a indu??o farmacol?gica do hipotireoidismo em c?es pode ser feita atrav?s da utiliza??o do metimazol. Novos e mais aprofundados estudos dever?o ser realizados utilizando-se esse paradigma experimental visando estabelecer as doses mais apropriadadas de metimazol em c?es.

Submitted by TIAGO SILVA DA FONSECA (tiago.odonto@hotmail.com) on 2018-08-15T13:52:28Z No. of bitstreams: 1 Tese - Tiago Silva da Fonseca.pdf: 3116289 bytes, checksum: 5bc17261ff2e5cf870764bac9df08bbb (MD5) / Approved for entry into archive by Ana Cristina Jorge null (anacris@fclar.unesp.br) on 2018-08-15T17:23:42Z (GMT) No. of bitstreams: 1 Fonseca_ts_dr_arafo_int.pdf: 3077264 bytes, checksum: 45ffe1976b230616d3be8df487229be6 (MD5) / Made available in DSpace on 2018-08-15T17:23:42Z (GMT). No. of bitstreams: 1 Fonseca_ts_dr_arafo_int.pdf: 3077264 bytes, checksum: 45ffe1976b230616d3be8df487229be6 (MD5) Previous issue date: 2018-03-28 / Fundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM) / Biodentine é um cimento reparador à base de silicato tricálcico com indicações semelhantes ao MTA. O objetivo deste estudo foi avaliar a resposta do periodonto ao selamento de perfurações de furca em molares de ratos com Biodentine ou MTA e as possíveis alterações séricas em marcadores de atividade hepática e renal. As perfurações realizadas nos primeiros molares da maxila direita de 60 ratos foram preenchidas com Biodentine, MTA ou algodão (Sham). As maxilas contralaterais do grupo Sham foram utilizadas como grupo Controle. Após 7, 15, 30 e 60 dias, o sangue foi coletado e as maxilas foram fixadas e incluídas em parafina (n=5). A partir do soro foram mensurados ou níveis de transaminase glutâmico-oxalacética (TGO), transaminase glutâmico-pirúvica (TGP), ureia e creatinina. O sangue de 5 animais sem qualquer procedimento foi coletado para mensurar os padrões sorológicos de referência. O espaço periodontal (EP), densidade de volume de células inflamatórias (VvCI) e de fibroblastos (VvFb) e o número de osteoclastos TRAP-positivos foram obtidos. Interleucina-6 (IL-6) e osterix foram detectados por imuno-histoquímica. O conteúdo de colágeno birrefringente foi quantificado a partir de cortes corados com picrosirius. Os dados foram submetidos à ANOVA e ao teste Tukey (p≤0,05). Diferenças significantes nos níveis séricos de TGO (p≥0,1258) e TGP (p≥0,5827) não foram detectadas nos grupos Biodentine, MTA e Sham em comparação aos níveis de referência. Aos 7 dias, a concentração de ureia sérica foi significantemente maior nos grupos Biodentine e MTA em comparação aos níveis de referência (p=0,0166). Um nível mais alto de creatinina sérica no grupo Biodentine aos 60 dias foi detectado em comparação aos valores de referência (p=0,0222). Aos 7 dias, os altos valores de VvCI, células IL-6-positivas e número de osteoclastos foram acompanhados por reduzido conteúdo de colágeno no EP alargado dos grupos experimentais. Em todos os períodos, VvCI, número de osteoclastos e de células IL-6-positivas e EP foram significantemente maiores em Sham que nos grupos Biodentine e MTA (p<0,0001). Do 7º ao 60º dia, significante redução de VvCI, expressão de IL-6 e osteoclastos foi acompanhada por significante aumento de VvFb, osteoblastos e conteúdo de colágeno nos grupos Biodentine e MTA. Aos 60 dias, diferenças significantes em VvCI, espessura do LP, imunoexpressão de IL-6 e número de osteoclastos e osteoblastos não foram detectadas entre Biodentine e MTA (p≥0,3255). Aos 30 e 60 dias, o número de osteoblastos osterix-positivos foi significantemente mais alto nos grupos Biodentine e MTA que no grupo controle (p<0,0001) enquanto diferenças significantes no número de osteoclastos não foram observadas (p≥0,8933). A análise bioquímica sugere que Biodentine e MTA não induzem mudanças hepáticas no decorrer do tempo. No entanto, é possível que mudanças renais sejam promovidas por Biodentine. Apesar da reação inflamatória e reabsorção óssea iniciais, o selamento de perfurações de furca com Biodentine e MTA promovem condições para o reparo periodontal. / Biodentine is a calcium silicate-based cement with similar indications of MTA. The aim of this study was to evaluate the periodontium response in the sealing of furcation perforations in rat molars with Biodentine and MTA, and its potential systemic effects in serum levels of hepatic and renal functions. The pulp chamber floor of right upper first molars of 60 rats were perforated and filled with Biodentine, MTA or sterile cotton pellet (Sham); the left first molars were used as control. After 7, 15, 30 and 60 days, the blood was collected and serum glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), creatinine and urea levels were measured. The blood of 5 rats without any treatment was collected to measure serum reference levels. The maxillary fragments were fixed and processed for paraffin-embedding. The periodontal space (PS), volume density of inflammatory cells (VvIC) and of fibroblasts (VvFb), and number of TRAP-positive osteoclasts were obtained. Interleukin-6 (IL-6), a pro-inflammatory cytokine, and osterix, an osteoblast marker, were detected by immunohistochemistry. The birefringent collagen content was quantified from picrosirius-stained sections. Data were submitted to ANOVA and Tukey test (p≤0.05). Significant differences in GOT (p≥0.1258) and GPT (p≥0.5827) serum levels were not observed in the Biodentine, MTA and Sham groups in comparison with reference levels. At 7 days, the concentration of serum urea increased significantly in the Biodentine and MTA groups compared with reference levels (p=0.0166). A higher concentration of serum creatinine in Biodentine group than reference level (p=0.0222) was detected at 60 days. At 7 days, the high values in VvIC, IL-6-immunolabelled cells and number of osteoclasts were accompanied by reduced collagen content in the enlarged PS of experimental groups. In all periods, VvIC, number of osteoclasts and IL-6, and PS were significantly higher in Sham than Biodentine and MTA groups (p<0.0001). From 7 to 60 days, significant reduction in VvIC, IL-6 immunoexpression and osteoclasts was accompanied by significant increase in VvFb, osteoblasts and collagen content in Biodentine and MTA groups. At 60 days, significant differences in VvIC, width of PS, IL-6 immunoexpression, in the number of osteoclasts and osteoblasts were not found between Biodentine and MTA (p≥0.3255). At 30 and 60 days, the number of osterix-immunolabelled osteoblasts was significantly higher in Biodentine and MTA than control group (p<0.0001) while significant differences in the number of osteoclasts were not observed (p≥0.8933). The biochemical analyses suggest that Biodentine and MTA did not induce changes in the liver over time. However, it is possible that kidney changes may be promoted by Biodentine. Despite the initial inflammatory reaction and bone resorption, the sealing of furcation perforations with Biodentine or MTA provide conditions to the periodontium repair. / FAPEAM 117/2014

Les maladies à prions sont des maladies neurodégénératives et transmissibles. Elles sont à l'origine de formes infectieuses comme la maladie de Creutzfeldt-Jakob iatrogène secondaire à un traitement par hormone de croissance d'origine humaine (MCJ post-hGH). La compréhension des facteurs gouvernant la physiopathologie de ces formes demeure parcellaire. Notre objectif a été de les étudier en analysant la cohorte des patients français exposés à l'hGH. Les analyses épidémiologiques, ont montré, à partir de données quantifiées, pour la première fois chez l'homme, une relation entre la dose d'exposition et le risque de développer la maladie d'une part et la durée de la période d'incubation d'autre part. La modélisation de la période d'incubation, a permis d'estimer que 95% des cas sont déjà apparus et d'évaluer l'influence du polymorphisme au codon 129 du gène codant la protéine prion sur la période d'incubation. L'étude descriptive a montré des similarités clinico-pathologiques entre tous les cas de maladies à prion humaines par contamination périphérique laissant supposer un rôle important de la voie d'exposition. Les expériences de transmission à la souris transgénique devraient permettre de valider les hypothèses que nous avons émises sur l'identité des souches présentes dans les lots contaminés. Ce travail a donc permis de mieux caractériser les facteurs impliqués dans la transmission des maladies à prions chez l'homme et de fournir un cadre méthodologique et des informations qui pourraient être utiles pour évaluer le risque de transmission potentielle des autres protéinopathies du système nerveux central pour lesquelles un mécanisme " prion like " a été proposé. / Prion diseases are fatal and transmissible neurodegenerative disorders. Infectious forms include iatrogenic Creutzfeldt-Jakob disease after human cadaver-sourced growth hormone treatment (hGH-iCJD). Our understanding of the factors governing the pathophysiology of infection, upon exposure to an exogenous prion, remains very limited in humans. The aim of this study was to better understand these phenomena using data from the French cohort of patients who were exposed to this at risk treatment. Using Cox hazards model, we provided the first epidemiological evidence of a relationship between dose of exposure and disease occurrence on one hand and incubation time on the other hand. Incubation period modelling by Weibull distribution estimated that 95% of the cases have already occurred. In a descriptive study, we showed that clinical and neuropathological features resembled other forms of infectious prion diseases after a peripheral contamination supporting a major role of the route of exposure. We also performed experimental transmission to transgenic mice expressing human PrP to test our hypotheses about the infecting prion strain that were transmitted to French hGH-iCJD patients. To conclude, we identified factors implicated in human prion transmission and provided a methodological frame and useful information that could help to evaluate the transmission risk associated with other brain proteinopathies such as Alzheimer and Parkinson’s diseases for which a prion-like mechanism has been proposed.