Tesis sobre el tema "Atropie"
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Koetz, Mariana. "Desenvolvimento e validação de métodos analíticos para determinação do teor de atropina em folhas de Atropa belladonna (L.) solanaceae". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/164716.
Texto completoAtropine is an alkaloid known for acetylcholine inhibition and as antimuscarinic substance and is present in leaves of some species of the family Solanácea, and especially of Atropa belladonna L. The importance of the production of herbal medicines in the pharmaceutical industry has driven scientific studies to develop analytical methods for quantification of chemical markers, present in herbal drugs, and that meet the quality control parameters of the current legislation. Thus, in this work, different methodologies for quantification of atropine (chemical marker predominant in the leaves of A. belladonna) were developed and validated. The methods proposed by High Performance Thin-layer Chromatography (HPTLC), High Performance Liquid Chromatography (HPLC) and Ultra Performance Liquid Chromatography (UPLC) were validated proving to have specificity/selectivity, linearity, precision, accuracy and robustness, and conforming to legislation. In addition, different extraction methodologies were proposed. For the first method of analysis (CCDAE), extraction with dilute acid (H2SO4 0.5 mol/L) followed by liquid-liquid extraction was used, resulting in an average content of 0.2913% atropine. For the second (HPLC), extraction with apolar solvent (methanol p.a.) was proposed, followed also by liquid-liquid extraction and with an average content of 0.2660% of the active. In the third (CLUE), optimization of extraction was done through Fractional Factorial Design, followed by Box-Behnken Design resulting in extraction by the apolar solvent mixture and Water (47% methanol), followed by solid phase extraction (silica) and an average atropine content of 0.3343%. An optimized extract was analyzed in three methods, resulting in atropine levels equal to 0.2905, 0.3598 and 0.3334 % for HPTLC, HPLC and UPLC, respectively. The review of the monograph of the plant material, with identification and physicochemical tests, together with the methodology of determination by HPLC was proposed with the objective of updating the methodologies that today compose the roadmap of quality control of specie in Brazilian Pharmacopoeia, which is in its 5th edition.
Dessalle, Kévin. "Régulation du métabolisme musculaire par les facteurs de transcription SREBP-1 : rôle des MRFs, de SIRT1 et des céramides". Phd thesis, Université Claude Bernard - Lyon I, 2012. http://tel.archives-ouvertes.fr/tel-00794521.
Texto completoBrasil, Antonio Augusto Azevedo Vital. "Atrofia prostática em espécimes de prostatectomia radical = há relação topográfica com neoplasia intraepitelial prostática alto grau e adenocarcinoma?" [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308454.
Texto completoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A relação entre a atrofia inflamatória com a neoplasia intraepitelial alto grau e o carcinoma, é controversa. Tem sido sugerida uma relação topográfica e que o epitélio proliferativo da atrofia inflamatória possa progredir para neoplasia intraepitelial prostática alto grau (NIPAG) e/ou carcinoma (CA). O propósito do nosso estudo foi analisar em espécimes de prostatectomia radical uma possível relação topográfica entre estas lesões. Um total de 3186 quadrantes pertencentes a 100 prostatectomias radicais completamente representadas, foi analisado. Determinou-se a frequência de quadrantes mostrando: somente atrofia inflamatória (AI), AI+CA, AI+NIPAG, ou AI+NIPAG+CA. A extensão e a distância entre as lesões foram avaliadas através de um método semiquantitativo de contagem de pontos previamente descrito. Também foram analisados focos de atrofia completa ou parcial sem inflamação. Os métodos estatísticos empregados foram os testes de Kruskal-Wallis e Mann-Whitney, e o coeficiente de correlação de Spearman. A média dos quadrantes exibindo somente AI, AI+CA, AI+NIPAG, e AI+NIPAG+CA foi 3.29, 2.51, 0.77, e 0.44; e a amplitude (0-21), (0-11), (0-6), (0-4), respectivamente (p<0.01). A maioria dos focos de AI estavam a uma distância >5mm dos focos de NIPAG e CA. Não houve correlação significativa entre a extensão da AI (p= 0.64, r= 0.05) com a extensão da NIPAG. Houve uma significativa correlação negativa entre a extensão da AI (p=0.01, r=-0.27) com a extensão do CA. Resultados similares foram encontrados considerando focos de atrofia com ou sem inflamação. Focos de atrofia parcial não evidenciaram inflamação crônica inespecífica. Nosso estudo não evidenciou associação topográfica significativa entre AI, NIPAG e/ou CA
Abstract: It is controversial whether there is any relationship of proliferative inflammatory atrophy (PIA) to high-grade prostatic intraepithelial neoplasia (HGPIN) and cancer (CA). It has been suggested a topographic relation and a potential of the proliferative epithelium in PIA to progress to HGPIN and/or CA. The aim of this study was to analyze in radical prostatectomies a possible topographic relation of the lesions. A total of 3186 quadrants from 100 whole-mount consecutive surgical specimens was examined. The frequency of quadrants showing: only PIA, PIA+CA, PIA+HGPIN, or PIA+HGPIN+CA was determined. Extent and distance between the lesions were evaluated by a semiquantitative point-count method previously described. We also studied foci with partial or complete atrophy without inflammation. The statistical methods included the Kruskal-Wallis and the Mann-Whitney tests and the Spearman correlation coefficient. The mean (range) of quadrants showing only PIA, PIA+CA, PIA+HGPIN, and PIA+HGPIN+CA was 3.29 (0-21), 2.51 (0-11), 0.77 (0-6), and 0.44 (0-4), respectively (p<0.01). Most of the foci of PIA were significantly located in a distance >5mm than <5mm from HGPIN or CA. There was no significant correlation between extent of PIA (p=0.64, r=0.05) with extent of HGPIN. There was a significant negative correlation of extent of PIA (p=0.01, r=-0.27) with extent of CA. Similar results were found considering foci either with or without inflammation. Chronic inespecific inflammation was not seen in foci of partial atrophy. A topographic relation of PIA to HGPIN and/or CA was not supported by our study
Mestrado
Anatomia Patologica
Mestre em Ciências Médicas
Fernandes, Daniela Alves 1985. "Relação entre volume hipocampal e volume de ressecção cirúrgica com controle de crises e desempenho de memória em pacientes com epilepsia de lobo temporal mesial submetidos a tratamento cirúrgico". [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309284.
Texto completoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A epilepsia é a segunda patologia neurológica que mais afeta a população mundial e a epilepsia do lobo temporal é a mais comum das epilepsias focais com maior frequência, associada à refratariedade e a distúrbios de memória. A lesão epileptogênica pode ser estudada através de imagens de ressonância magnética (RM), EEG entre outros exames, facilitando a indicação da cirurgia que tem como objetivo reduzir as crises, entretanto a função cognitiva pode ser afetada. Nosso propósito foi avaliar a eficácia da cirurgia quanto ao controle das crises, desempenho de memória nos pacientes e comparar os resultados de avaliações neuropsicológicas pré e pós-operatórias quanto à frequência de crises, abordagem cirúrgica e volumetria da estrutura e lacuna. Foram analisados 55 pacientes submetidos à cirurgia de epilepsia e 29 indivíduos controles saudáveis. Todos foram submetidos à aquisição de imagens em um aparelho de RM 2T em dois tempos com intervalos médios de 4,4±2,8 anos. A volumetria do hipocampo e lacuna cirúrgica foi realizada com o software Display, utilizando o protocolo de Bonilha et at., 2004. Os pacientes foram avaliados de acordo com a classificação pós-operatória de Engel Jr., 1997 e testes de avaliações neuropsicológicas que incluiu subtestes: da Wechsler Memory Scale-Revised; Wechsler Adult Intelligence Scale-Revised e Rey Auditory Verbal Learning Test, realizados com um intervalo médio de 8,5 anos após a cirurgia. Para análise dos dados pré/pós-operatórios foi utilizado o teste T de Student, de Wilcoxon ou Man-Whitney, correlação de Pearson e Spearman de acordo com as características das variáveis. Observamos diferença significativa nas avaliações neuropsicológicas, quando comparadas entre os próprios indivíduos nos grupos pré e pós-operatório e nos grupos de acordo com a Escala de Engel e lado da cirurgia, com piora no desempenho cognitivo no período pós-operatório. Mostraram melhora no desempenho de memória os que foram classificados em Engel IA quando comparados aos indivíduos que continuaram com crises. Os grupos submetidos à amigdalohipocampectomia seletiva e ressecção cortical associada à amigdalohipocampectomia não apresentaram diferenças significativas quanto ao desempenho de memória. O grau de escolaridade influenciou negativamente no resultado das avaliações. Nossos resultados mostraram que 80% foram classificados em Engel I, 18,2% em Engel II e 1,8% em Engel III. A volumetria dos hipocampos direito e esquerdo ipsilaterais à cirurgia apresentaram valores menores que dos controles. Os hipocampos esquerdos e direitos pré/pósoperatórios contralaterais à atrofia não apresentaram resultado significativo quando comparado as volumetrias dos controles e nem quando comparados entre si. Os dados de volumetria associados à memória apresentaram grau razoável e moderado de correlação. Nossos resultados mostraram que após a ressecção cirúrgica existe um declínio no desempenho de memória, porém a frequência de crises desses pacientes diminui significativamente e que o tipo de abordagem cirúrgica não interfere no desempenho de memória, mesmo com o maior volume da ressecção de pacientes submetidos à lobectomia temporal anterior
Abstract: Epilepsy is the second most frequent neurological disease and temporal lobe epilepsy is the most common form of focal epilepsy and is more frequently associated to refractoriness and memory decline. The epileptogenic lesion can be studied through magnetic resonance imaging, EEG and other tests, facilitating the indication of surgery that aims to reduce seizure frequencies, however cognitive function may be affected. We proposed to evaluate the effectiveness of surgery on the management of seizures, memory performance and compare the results of neuropsychological assessments pre/post-operative and the frequency of seizures, surgical approach and volume of hippocampi and amount of resection. We analyzed 55 patients who underwent epilepsy surgery and 29 healthy control subjects. All patients underwent imaging in a 2T MR scanner in two steps with intervals of 4.4 ± 2.8 years. The volumetry of the hippocampus and surgery gap was done with the software display, using the protocol described by Bonilha et al, 2004. Patients were evaluated according to the postoperative classification of Engel Jr., 1997 and neuropsychological evaluation that included the subtests, Wechsler Memory Scale-Revised, Wechsler Adult Intelligence Scale-Revised and Rey Auditory Verbal Learning Test, performed with an average interval 8.2 years after surgery. For data analysis, pre/post-operative we used the Student t test, Wilcoxon or Man-Whitney, Pearson and Spearman correlation test according to the characteristics of variables. We observed significant differences in neuropsychological evaluations, when we compared the groups pre/post-operative and the groups according to the Engel Scale and side of surgery, with worsening of cognitive performance in the postoperative period. There was a relative improvement in memory performance in those who were classified as Engel IA compared to individuals who continued to have seizures. The comparisons between the groups of selective amygdalohippocampectomy and anterior temporal lobe resection showed no significant differences in memory performance. The level of education had a negative influence on the outcome of neuropsychological evaluations. Our results showed that 80% were classified as Engel I, 18.2% in Engel II and 1.8% in Engel III. The volumetry of the left and right hippocampi ipsilateral to the surgery showed lower values than controls. The left and right hippocampus pre/post-operative contralateral to the side of surgery did not show significant differences when compared to controls. There was a correlation between hipocampal volumes and memory performance. Our results showed that after surgical resection there is a decline in memory performance, but the frequency of seizures in these patients decreased significantly and that the types of surgical approaches do not differ in terms of post-operative nor the total volume of the surgical lacunae
Mestrado
Neurociencias
Mestre em Ciências
Freire, Simei André da Silva Rodrigues 1981. "Tratamento de fraturas de mandíbulas atróficas : estudo epidemiológico, mecânico e análises de elementos finitos". [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/289615.
Texto completoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: O objetivo desse trabalho foi avaliar a epidemiologia e características do tratamento de fraturas de mandíbula atrófica; comparar a resistência mecânica e a distribuição de tensões de três técnicas de fixação interna aplicadas em fraturas de mandíbulas atróficas. CAPÍTULO I: Dados foram coletados de pacientes vítimas de fraturas em mandíbulas atróficas em um período de dez anos (1999-2009). Os dados analisados continham informações demográficas e socioeconômicas, etiologia dos traumas, diagnóstico, tipos de traumas, deslocamento das fraturas, o método de fixação utilizado, região das fraturas, traumas associados, tempo decorrido entre o trauma e tratamento. A principal causa das fraturas em mandíbulas atróficas foi a queda da própria altura, acometendo principalmente pacientes do gênero masculino desempregados. A faixa etária mais acometida foi a de trinta a sessenta anos ocorrendo predominantemente fraturas bilaterais na região de corpo mandibular. CAPÍTULO II: Avaliou-se a resistência, in vitro, por meio de testes de carregamento linear a fixação de fraturas de mandíbulas atróficas com defeito de continuidade por meio de três sistemas de fixação. Foram utilizadas réplicas de mandíbulas humanas atróficas de poliuretano submetidas a simulação de fratura com defeito de continuidade de 15mm em corpo direito, fixadas pelos seguintes sistemas: Grupo 1 - sistema 2,4mm conventional, Grupo 2 - sistema 2,4 mm com travamento e Grupo 3 - sistema 2,0mm com travamento. Pelos resultados obtidos o sistema com travamento aumentou a resistência da fixação pela melhor e mais favorável distribuição de cargas, os sistemas 2,4mm de fixação interna estável testados apresentaram adequada resistência mecânica para tratamento de fraturas de mandíbulas atróficas com defeito de continuidade. CAPÍTULO III: Avaliou-se, in sílico, pelo método de elementos finitos a fixação de fraturas de mandíbulas atróficas por meio de três sistemas de fixação submetidas a testes de carregamento linear. Os modelos criados em elementos finitos de fratura de mandíbula atrófica foram fixados pelos seguintes sistemas, sistema 2,4mm convencional, sistema 2,4mm com travamento e sistema 2,0mm com travamento. Pelos resultados obtidos o sistema 2,4mm convencional demonstrou suportar toda carga aplicada nesta simulação, os sistemas com travamento apresentaram dissipação das tensões para região anterior e posterior da mandíbula e no sistema de fixação convencional as tensões se localizaram na porção entre os furos do sistema de fixação assim como no sistema com travamento, porém este ainda apresentou dissipação para os parafusos, com concentração crescente para região apical dos parafusos próximos a simulação do traço de fratura
Abstract: The aim of this study was to evaluate the epidemiology and treatment characteristics of atrophic mandibular fractures; to compare the mechanical strength and stress distribution of three internal fixation techniques applied in atrophic mandibles fractures treatment. CHAPTER I: Data were collected from patients suffering from atrophic mandibles fractures in a period of ten years (1999-2009). The data analyzed contained demographic and socioeconomic characteristics, etiology of trauma, diagnosis, types of trauma, displacement of the fractures, the region of fracture, associated trauma, time elapsed between trauma and treatment. The main cause of fractures in atrophic mandibles was fall accidents, affecting mainly male unemployed patients. The age group most affected was between thirty to sixty years occurring bilateral fractures predominantly in the mandibular body region. CHAPTER II: Resistance was evaluated in vitro by linear loading test in the atrophic mandible fracture simulation with continuity defect by three stable internal fixation systems. It was used replicas of human atrophic polyurethane mandible subjected to simulated fracture defect continuity of 15mm in right body region, fixed by the following systems: Group 1 - 2.4mm conventional system, Group 2 - 2.4 mm locking system and Group 3 - 2.0mm locking system. The results obtained with the locking system increased the resistance setting for the better and more favorable load distribution, the 2.4mm stable internal fixation systems tested had adequate mechanical strength for the treatment of fractures of atrophic mandibles with continuity defects. CHAPTER III: It was evaluated ,in silico, by the method of finite elements with linear force three stable internal fixation systems for the treatment of atrophic mandible fractures. The finite element models created in the atrophic mandible fracture were fixed by the following systems, the conventional system 2.4mm, 2.4mm locking system and 2.0mm locking system. The results obtained demonstrated that the locking system increased the resistance by a favorable and better distribution of the stresses during the loading test when applied in atrophic mandible fractures with continuity defects. The three internal fixation systems tested in this study showed adequate mechanical efficiency to be applied in atrophic mandible fractures with continuity defects treatment
Doutorado
Cirurgia e Traumatologia Buco-Maxilo-Faciais
Doutor em Clínica Odontológica
Fernandes, Daniela Alves 1985. "Avaliação da tractografia, relaxometria T2 e volumetria hipocampal e sua relação com o controle de crises e alterações de memória em pacientes com epilepsia de lobo temporal mesial submetidos ao tratamento cirúrgico = Tractography assessment, T2 relaxometry and hippocampal volume and its relation to the control of seizures and memory impairment in patients with mesial temporal lobe epilepsy underwent surgical treatment". [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312638.
Texto completoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A quantificação da atrofia das estruturas temporais mesiais pelas imagens de RM em pacientes com ELTM permite a identificação "in vivo" das alterações anatômicas associadas à esta patologia e sua correlação com dados neuropsicológicos, permitem a definição de um bom diagnóstico. Apesar da comprovação da eficácia do tratamento cirúrgico para o controle das crises, ainda não são claros os efeitos da ressecção de estruturas mesiais do lobo temporal na performance cognitiva, a longo prazo. O objetivo deste trabalho foi realizar um estudo prospectivo de uma série de pacientes com ELTM submetidos ao tratamento cirúrgico, comparando os resultados pré/pós-cirúrgicos obtidos a partir da análise de dados de avaliação neuropsicológica (ANP) e imagens de RM. No estudo avaliamos 119 indivíduos, 88 pacientes e 31 controles saudáveis. Os pacientes foram classificados de acordo com a escala proposta por Engel para controle de crises após a cirurgia. Avaliamos o coeficiente de inteligência estimado (QIe), as memórias verbal e não verbal com testes utilizados na rotina de investigação pré-operatória do nosso serviço. Utilizamos análises longitudinais específicas realizadas com o software SPSS®22. Consideramos p?0,05. Quanto à classificação de Engel observamos que 73,7% dos pacientes foram classificados em Engel I; 17,1% foram classificados em Engel II; 8,0% foram classificados em Engel III e 1,1% classificado em Engel IV com tempo médio de seguimento de 8,8 anos após a cirurgia. Para as ANP pré/pós-operatória observamos um declínio de memória para esses pacientes relacionado ao controle de crises e lado da cirurgia (p<0,0001). Para as ANP pós-operatórias realizadas em dois tempos diferentes e separadas em grupos quanto ao controle de crises e lado da cirurgia, não observamos diferença significativa, entretanto todos os testes indicaram uma tendência de melhora no desempenho de memória e QIe. Observamos maior volume hipocampal para os controles (média=3706±842), volume reduzido do hipocampo contralateral para pacientes livre de crises (média=3602±711) e menor ainda para os pacientes com presença de crises (média=3284±521). Para a análise de intensidade de sinal no lobo temporal contralateral dos pacientes, observamos uma diferença significativa (p=0,005) entre controles e pacientes com média menor para os controles. Também observamos alterações com diferença significativa para os tratos analisados em imagens de DTI, no lado ipsilateral à cirurgia comparados aos controles. Nossos resultados mostram bom controle de crises após a cirurgia, mesmo após um longo período. Entretanto observamos que após a cirurgia existe um declínio na performance dos testes neuropsicológicos para muitos pacientes, independente do lado operado. Porém, a análise a longo prazo mostra que existe uma recuperação parcial desse declínio, que pode estar associada a interação entre fatores de aprendizado e plasticidade cerebral; ou seja, podemos inferir que de alguma forma a melhora no controle das crises permite uma "recuperação" da eficiência cognitiva a longo prazo
Abstract: The quantification of the atrophy of the mesial temporal structures by MR images in patients with TLE allows identification "in vivo" of the anatomical changes associated with this disease and its correlation with neuropsychological data, allowing for the establishment of a proper diagnosis. Despite the evidence of the effectiveness of surgical treatment for seizure control, it is not yet clear the effects of resection of the mesial temporal lobe structures in cognitive performance in the long-term follow up. The aim of this study was to evaluate prospectively of a series of patients with TLE undergoing epilepsy surgery, comparing pre/post-surgical results obtained from neuropsychological assessment (NPA). We included 119 subjects, 88 patients and 31 healthy controls. Of the 113 patients, 88 had two NPA and 60 underwent two MRIs after surgery. Patients were classified according to Engel¿s scale. We evaluated the estimated intelligence coefficient (eIQ), the verbal and non-verbal memories with tests used in preoperative routine. We use specific longitudinal analyzes with SPSS®22 software. We observed that 73.7% of patients were classified as Engel I; 17.1% were classified as Engel II; 8.0% were classified as Engel III and 1.1% classified as Engel IV after surgery with a mean follow up of 8.8 years. The NPA pre/postoperative showed a memory decline for these patients related to seizures control and side of surgery (p<0.0001). We found no significant difference between the postoperative NPAs carried out in two different times and separated in groups regarding seizure control and side of surgery; however, all tests indicated a trend towards improvement trend in memory performance and eIQ. We observed a larger hippocampal volume for the controls (mean=3706±842), in comparison with seizure free patients (mean=3602±711) and smaller hippocampal contralateral volumes for patients with persistent seizures after surgery (mean=3284±521). We observed a significant difference (p=0.005) in T2 signal between patients and controls (increase in patients). We also observed changes with a significant difference to the white matter tracts analyzed with diffusion tensor images, in the ipsilateral side of surgery compared to controls. Our results show good seizure control after surgery, even after a long period of follow up. However, our results showed that after surgery there is a decline in the performance on neuropsychological tests for most patients, regardless of the side of surgery. However, the long-term repeated analysis showed that there is partial recovery that may be associated with the interaction between learning effect and brain plasticity. We can hypothesize that the improvement in seizure control after surgery allows "recovery" of the long-term cognitive efficiency
Doutorado
Fisiopatologia Médica
Doutora em Ciências
Dibenedetto, Silvia. "Direct activation of endogenous Calcineurin A : biological impact of selective peptide aptamers". Phd thesis, Ecole normale supérieure de lyon - ENS LYON, 2011. http://tel.archives-ouvertes.fr/tel-00757018.
Texto completoPinheiro, Clara Maria [UNESP]. "Efeito da inflamação do tornozelo sobre as características histológicas, a expressão gênica e níveis da creatina cinase nos músculos sóleo e tibial anterior de ratos diabéticos". Universidade Estadual Paulista (UNESP), 2011. http://hdl.handle.net/11449/87973.
Texto completoConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Universidade Estadual Paulista (UNESP)
O Diabetes mellitus é um dos mais importantes problemas de saúde pública, ocasionando complicações crônicas como a atrofia muscular e perda da qualidade de vida do paciente. Quando ocorre uma lesão articular, o músculo responde com um processo de atrofia onde é gerada uma modificação no tecido muscular funcionalmente relacionado com essa articulação. Contudo, estudos experimentais que contribuam ao esclarecimento da relação entre inflamação articular e as modificações histológicas e da expressão gênica do músculo de animais diabéticos não têm sido desenvolvidos. Outro parâmetro importante que deve ser estudado é a atividade da enzima creatina cinase (CK) uma vez que sua atividade pode ser alterada em função de várias causas como na injúria, distrofia, inflamação ou necrose da musculatura esquelética ou cardíaca. O presente projeto teve por objetivo estudar o efeito da inflamação aguda do tornozelo sobre os músculos Sóleo (SO) e Tibial Anterior (TA), investigando a presença de alterações histológicas, alterações na expressão gênica dos atrogenes atrogina-1e MuRF-1 e na atividade da creatina cinase em músculos de ratos não-diabéticos e diabéticos com e sem tratamento insulínico. Foram estudados 54 ratos Wistar (150g). A indução do diabetes foi por via intrapenitoneal com 50mg de estreptozotocina (STZ) por Kg de peso corporal, dissolvida em tampão citrato pH 4,5. Para a inflamação a articulação do tornozelo foi mantida em 90° localizando a fossa distal e posterior ao maléolo lateral, introduzindo nesta zona uma agulha de diâmetro 26 com 0.03ml carragenina a 3%. Os grupos de animais diabéticos com terapia insulínica foram tratados duas vezes ao dia (as 8h e 17h) com 2,5 U de insulina NPH durante 13 dias, totalizando 5U/dia A insulina foi administrada por via subcutânea...
Diabetes mellitus is one of the most serious public health problems, which diminishes the quality of life of the patient and leads to many chronic complications, one of which is muscle atrophy. When a joint is injured, the muscle responds with a process of atrophy in which a change occurs in the muscle tissue functionally related to the joint. However, no experimental studies have been carried out to clarify the relationship between joint inflammation and changes in the histology and gene expression of muscles in diabetic animals. Another important variable that should be studied is the activity of the enzyme creatine kinase (CK), since it can be altered under various conditions, such as injury, muscular dystrophy, inflammation or necrosis of skeletal or heart muscle. The aim of this project was to study the effect of acute inflammation of the ankle on the soleus (SO) and tibialis anterior (TA) muscles, by noting the histological changes, changes in the expression of the atrophy-related genes (atrogenes) atrogin-1 and MuRF-1 and activity of CK in muscles of non-diabetic and diabetic rats, treated and untreated with insulin. We studied 54 Wistar rats (150g). Diabetes was induced by intraperitoneal injection of 50mg streptozotocin (STZ) per kg body weight, dissolved in citrate buffer (pH 4.5). To induce inflammation, the ankle joint was held at 90°, with the fossa located distal and posterior to the lateral malleolus, and inserting a 26-gauge needle into this region, with 0.03mL of 3% carrageenan. The groups of insulin-treated diabetic animals were treated twice a day (at 8 am and 5 pm) by subcutaneous injection with... (Complete abstract click electronic access below)
Moucheront, Nicolas. "Le Palais des doges de Venise à l'époque moderne (1595-1625) : la conclusion d’un grand chantier". Electronic Thesis or Diss., Paris, EHESS, 2024. http://www.theses.fr/2024EHES0014.
Texto completoThe gothic Venice Ducal Palace was realized for 1340 but all the last centuries of Middle Ages long and for whole Renaissance, works have gone ahead seamless. Around 1625, the building reach its actual design and till this moment, only restoration works have been realized. This PhD tesis in architecture history studies the conclusive moment of this building process in order to understand why and how for 1595 so big a building site achieves. Financing dynamics of public works in Venice are first of all inserted within a long term analysis from the amortization of public debt between Middle Ages and Modern times. Such a study consent to pass in review thanks to available publications the main steps of the Ducal Palace building and to advocate a financial study of some of the major public buildings in Venice late XVIth century such as Rialto bridge or Redentore church.This study on the institutional functions of the Salt Office is in a second moment addressed to a specific political moment for the Venice Republic, the Interdetto crisis. A series of biographic researches about public and private commissions of several doges on power from 1595 to 1625 is developed, focusing on the respective leaders from the pro papalist vecchi and their opponents, the giovani patricians, Marino Grimani and Leonardo Donà. Specific research on public records and family archives are also dedicated to the exceptional journey from Padua to Paris of Antonio Priuli. Indeed, as Surveyor from all the Ducal palace places, he is responsible for the transformation of this building between 1601 and 1614. Then, he relaunches the works when arriving on power from 1618 till his death in 1624. During all this time long, the carpenter Bartolomeo Manopola conducts the works as Salt office proto. A detailed study is realized on his family building firm associating stone carvers, carpenters and masons. The relationships between public building and important figures from the time such as the stone carver Giovanni Grapiglia, the architect Vincenzo Scamozzi and the art seller Daniel Nijs are also developed associating a study on the commissioners network, architecture details and building site accounts. Such a micro-historic approach from the productive structure of the building site is the base for an analysis from the superstructure, ie for a survey on the Ducal palace architecture transformations from 1595 to 1625.Internal conflicts enable an interpretation of the functional program for the room gradually arranged on the ground floor on the building and inside the lodges. The powers representations shaped on on the clock facade and inside the new banqueting room are then analyzed through a political length, considering the difficult situation resulting from the Gradisca war and the hot moment of the Bedmar plot in 1618, just when Antonio Priuli finally became doge. An opening chapter concludes the tesis putting the Ducal palace transformations within the current transformation cycles of the other headquarters of the Venitian power in Main Land and Sea Land main towns. The aim is to catch the political function from architecture design process in a Republic. Public palaces are sophisticated representations from power. Theirs material transformations are as a consequence the tools from complex negotiations in grade of overall political crisis moments
Maessen-Visch, Marjolein Birgitte. "Atrophie blanche". [Maastricht : Maastricht : Universiteit Maastricht] ; University Library, Maastricht University [Host], 1999. http://arno.unimaas.nl/show.cgi?fid=6721.
Texto completoAppenzeller, Simone 1974. "O sistema nervoso central no lupus eritematoso sistemico : analises clinica e de ressonancia magnetica". [s.n.], 2006. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310433.
Texto completoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: As manifestações do sistema nervoso central (SNC) no Lúpus Eritematoso Sistêmico (LES) são complexas, podendo ser causadas diretamente pela atividade do LES ou serem secundárias a comorbidades. O nosso objetivo foi avaliar as manifestações do SNC no LES e orrelacioná-las às alterações cerebrais estruturais e funcionais à ressonância magnética. Todos os pacientes preenchiam quatro ou mais critérios classificatórios de LES e foram selecionados no ambulatório de Reumatologia da UNICAMP. Observamos que crises epilépticas ocorreram em 11,6% dos pacientes, estando associadas a acidente vascular cerebral e a presença de anticorpos antifosfolípides. A recorrência de crises foi rara, associada somente a presença de anticorpos antifosfolípides. A migrânea ocorreu mais frequentemente no LES que no grupo controle e estava associada a atividade de doença, ao Fenômeno de Raynaud e a presença de anticorpos antifosfolípides. Pacientes com história pregressa de migrânea apresentavam mais dano permanente. Analisando as ressonâncias magnéticas em pacientes com LES, observamos tanto atrofia de substância branca como de substância cinzenta. Embora ambos estivessem associados à presença de manifestações pregressas do SNC e ao maior tempo de doença, somente a atrofia de substância cinzenta esteve associada à dose cumulativa de corticosteróides. Pacientes com distúrbios cognitivos apresentaram mais frequentemente atrofia de corpo caloso e de hipocampo. Observamos também uma disfunção axonal no LES, associada a atividade de doença. De acordo com os nossos resultados, os métodos de neuroimagem estruturais e funcionais são úteis na confirmação do envolvimento do SNC e também na identificação do envolvimento subclínico no LES
Abstract: Central nervous system (CNS) manifestations in systemic lupus erythematosus (SLE) arecomplex. They may be directly caused by SLE disease activity or may be secondary to comorbities. Our objective was to determine CNS manifestations in SLE patients and to determine structural and functional neuroimaging abnormalities associated with its occurrence. Patients with four or more classification criteria for SLE, followed at the Rheumatology Unit of the State University of Campnas were included. We observed 11.6% of epileptic seizures in SLE patients. The occurrence of epileptic seizures was associated with the presence of stroke and antiphospholipid antibodies. Recurrence of seizures was rare and associated only with the presence of antiphospholipid antibodies. Migraine was more frequently observed in SLE patients than controls and was associated with disease activity, Raynaud¿s phenomenon and antiphospholipid antibodies. Pacients with past history of migraine had more frequently organ damage. We observed white and gray matter atrophy in SLE patients. Although both were associated with disease duration and past history of CNS involvement, only gray matter atrophy was associated with the total corticosteroid dose. Patients with cognitive impairment had more frequently corpus callosum and hippocampal atrophy. A transient axonal dysfunction, secondary to disease activity and not to CNS involvement, was observed in SLE. Our results suggest that structural and functional neuroimaging methods are useful in confirming CNS involvement, but also identify subclinical involvement in SLE patients
Doutorado
Clinica Medica
Doutor em Clínica Médica
Fernandes, Tatiane Rosa 1981. "Influencia do uso tópico do estrogênio ou testosterona ou acido poliacrilico sobre a funçao sexual em mulheres na pós menopausa = ensaio clinico controlado e aleatorizado = Eficcacy of vaginally applied estrogen, testosterone, polyacrylic acid on sexual function in postmenopausal women: a randomized controlled trail". [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/313671.
Texto completoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: A atrofia vaginal é uma condição crônica frequente em mulheres na pós-menopausa que acarreta alterações em sua sexualidade e consequentemente em sua qualidade de vida. Recentes estudos avaliam novas alternativas de tratamento para essa ascendente queixa da população feminina. Entretanto, atualmente dispomos de poucas opções terapêuticas adequadamente avaliadas. Objetivo: Comparar a função sexual feminina após o uso tópico de estrogênio, testosterona e ácido poliacrílico com o uso de lubrificante vaginal. Métodos: Ensaio clinico randomizado com 80 mulheres na pós-menopausa, entre 40 e 70 anos, em seguimento no Ambulatório de Menopausa do CAISM Unicamp. As mulheres foram randomizadas para o tratamento tópico via vaginal com estrogênio, testosterona, ácido poliacrílico e lubrificante, três vezes na semana, por um período de 12 semanas, entre novembro de 2011 a janeiro 2013. Utilizou-se o Índice de Função Sexual Feminina para avaliar as mudanças da resposta sexual no início e após 6 e 12 semanas. Resultados: O ácido poliacrílico e a testosterona tópica, em comparação com o lubrificante após 12 semanas de tratamento, apresentaram aumento nos domínios: desejo sexual, lubrificação, satisfação, dor na relação sexual e escore total. O tratamento com o estrogênio tópico em comparação com o lubrificante apresentou melhora no domínio desejo. A análise intragrupo ao longo do tempo de tratamento evidenciou melhora nos domínios desejo, lubrificação, dor para as mulheres que utilizaram ácido poliacrílico, testosterona e estrogênio. Além disso, as mulheres que utilizaram testosterona apresentaram melhora ao longo do tempo nos domínios excitação, orgasmo e satisfação. Conclusão: O tratamento por 12 semanas- em mulheres na pós-menopausa com sintomas de atrofia vaginal - realizado com ácido poliacrílico, testosterona e estrogênio demonstrou melhora na função sexual feminina. quando comparado ao uso de lubrificante vaginal
Abstract: Introduction. Female libido is multifactorial and complex. Declining estrogen levels in postmenopausal women affects vaginal function. Aim. To evaluate female sexual function after using topical estrogen, testosterone or polyacrylic acid as vaginal lubricants with K-Y jelly as a placebo lubricant. Methods. This was a randomized controlled clinical trial on 80 postmenopausal women between 40 and 70 years of age with follow-up at the Menopause Clinic of the CAISM / Unicamp. The women were randomized to treatment with topical vaginal estrogen, testosterone, polyacrylic acid or oil lubricant alone, three times a week for a period of 12 weeks from November 2011 to January 2013. Main Outcome Measures. We used the Female Sexual Function Index (FSFI) to assess changes in sexual response at baseline, and after 6 and 12 weeks. Results. After 12 weeks of treatment, polyacrylic acid and topical testosterone produced improvements in the FSFI domains of sexual desire, lubrication, satisfaction, reduced pain during intercourse and total score compared with lubricant alone. Treatment with topical estrogen in comparison with lubricant alone showed an improvement in the FSFI field of desire. The intragroup analysis over the time of the treatment showed improvements in the fields of desire, lubrication, and reduced pain for polyacrylic acid, testosterone and estrogen. Furthermore, women who used testosterone showed improvements over time in the fields of arousal, orgasm and satisfaction. Conclusions. Treatment of postmenopausal women with symptoms of vaginal atrophy with polyacrylic acid, testosterone and estrogen for 12 weeks produced improvements in self-reported female sexual function when compared with a lubricant
Mestrado
Fisiopatologia Ginecológica
Mestra em Ciências da Saúde
Ratti, Francesca. "Role of HDAC6 in Skeletal Muscle Atrophy". Thesis, Lyon, École normale supérieure, 2014. http://www.theses.fr/2014ENSL0887.
Texto completoHDAC6 is a highly conserved histone deacetylase, mostly cytoplasmic. Unlike other deacetylases, HDAC6 has unique substrate specificity for non-histone proteins. Besides the deacetylation domains, HDAC6 also contains an ubiquitin-binding domain, which links HDAC6 to the ubiquitin/proteasome pathway. Skeletal muscle atrophy is a severe condition of muscle mass loss occurring during aging or in many clinical disorders as cancer, diabetes and AIDS. The maintenance of muscle mass is subtly controlled by an equilibrium between catabolic and anabolic processes. Muscle atrophy results as a partial suppression of protein synthesis and a substantial increase of protein breakdown by the ubiquitin-proteasome system, caused by the expression of a series of specific genes, the atrogenes. One of the atrogenes induced more dramatically is the muscle specific E3 ubiquitin ligase MAFbx/Atrogin-1, which takes care of the degradation of MyoD and of eIF3-f. Degradation of those two proteins inhibits expression of myotrophic genes and translation preventing the replacement of degraded proteins.We identified HDAC6 as a new atrogene. HDAC6 expression is up regulated during muscle atrophy in mouse and human through a mechanism FoxO3-dependent. In vivo depletion of this enzyme by shRNA electroporation or homologous recombination gives protection against atrophy and its inhibition during atrophy can partially reverse the muscle wasting phenotype. HDAC6 can interact with MAFbx and is required for MAFbx-mediated degradation of MyoD. According to our results, forced expression of a MyoD mutant resistant to HDAC6 and MAFbx dependent degradation prevents muscle wasting induced by denervation. Furthermore, some preliminary data show an involvement of HDAC6 in the degradation of eIF3-f and in the autophagy process in muscle tissue, revealing a double role of HDAC6 in skeletal muscle.These evidences suggest that HDAC6 potentially represents a valuable target for curative treatments
Catteau, Matthias. "Le microenvironnement cellulaire : un frein aux effets du réentraînement à l'effort chez le patient BPCO ?" Thesis, Montpellier, 2019. http://www.theses.fr/2019MONT4002.
Texto completoMuscle dysfunction is one of the major comorbidity touching patients suffering from chronic obstructive pulmonary diseases (COPD). More than a physical handicap, muscle dysfunction is an indicator of survival in COPD patients. To restore functional capacities and effort tolerance, exercise training (ET) during a pulmonary rehabilitation program represents the best therapeutic approach. However, the beneficial effects induced by ET are limited both in intensity and time. This limitation is a major issue in the therapeutic strategy of COPD patients. One of the hypothesis that could explain these limitations is that the « Spill-over » of inflammatory molecules coming from the lung, into the systemic circulation, could instigates the deterioration of muscle microenvironment and limits the beneficial effects of ET.The objective of the thesis project is to study the role of the muscle cell microenvironment of COPD patients in the defective regeneration processes and to assess the implication of COPD microenvironment in the limited beneficial effects of ET.We have shown that autophagy, modulated by oxidative stress, was implicated in the alteration of COPD muscle cells in culture. We studied if the COPD microenvironment (COPD serum) could participate to the alterations of differentiation/regeneration processes of healthy human myoblasts. We then established an in vitro methodology allowing to study the effects of the COPD microenvironment on the healthy human myoblast differentiation. Using this approach, we have shown that severity of the disease affects the microenvironment composition, with an impact on the myoblast differentiation. It is probably due to an exhaustion of myogenic capacities by the COPD microenvironment. The ET seems to not be able to restore a suitable microenvironment composition for differentiation, promoting the expression of catabolism markers. We also observed that myoblasts from COPD patients exhibited defects of adaptation in response to an electrical stimulation (inducing similar adaptative responses to ET) suggesting that COPD myoblasts had an altered myogenic potential.This work suggests that COPD microenvironment drives some molecules that could leads to an exhaustion of myogenic potential of healthy human myoblasts. This effect of the microenvironment could finally lead to an altered muscle regeneration processes and limit the beneficial effects of ET in the COPD patient
Aniort, Julien. "Mécanismes de l'atrophie musculaire au cours de l'insuffisance rénale". Thesis, Université Clermont Auvergne (2017-2020), 2018. http://www.theses.fr/2018CLFAS024.
Texto completoRésumé indisponible
Bovi, Ana Carolina Nunes. "Progressão da atrofia hipocampal e do corpo caloso em pacientes com epilepsia de lobo temporal submetidos a tratamento medicamentoso ou cirúrgico". [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309287.
Texto completoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Epilepsia do Lobo Temporal (ELT) é uma doença que apresenta atrofia das estruturas mesiais temporais, como resultado da esclerose mesial temporal (EMT), presente em 60-70% dos casos em que a cirurgia é a mais recomendada. A ELTM associada EMT possui um alto grau de refratariedade, em que pequena percentagem de indivíduos alcança o controle das crises, uma vez que a causa do EMT é desconhecida. Muitos estudos mostram que a atrofia do hipocampo contralateral ao foco epileptogênico também sofre alterações. A ressonância magnética tem sido uma ferramenta fundamental para o diagnóstico e quantificação dessas mudanças. Assim, o estudo avaliou 60 pacientes, sendo 30 indivíduos em tratamento medicamentoso e 30 em tratamento cirúrgico, com o objetivo de avaliar e quantificar essas alterações morfológicas encontradas nas estruturas envolvidas na ELTM por meio de um software manual que permite o traçado das estruturas e a sua associação com os achados clínicos da doença, a fim de elucidar o impacto dos tratamentos clínico e cirúrgicos. Os resultados mostraram que o grupo controle não apresentou progressão da atrofia tanto o hipocampo considerado menor (p = 0,533), o hipocampo considerado maior (p = 0,494) e nem do corpo caloso (p = 0,260). A análise do grupo clínico identificou uma redução no volume do hipocampo, tanto ipsilateral quanto contralateral nos dois subgrupos, refratários e benignos, e em relação ao hipocampo ipsilateral (atrófico) ocorreu redução volumétrica significativa no subgrupo benigno (p = 0,001) e também no subgrupo refratário (p = 0,003). O hipocampo contralateral ao foco epileptogênico no grupo CLR apresentou um grau significativo de atrofia (p = 0,001) sendo que o mesmo ocorreu com o subgrupo CLB (p = 0,011). No grupo cirúrgico (CX), o hipocampo contralateral (remanescente/saudável) mostrou uma progressão de atrofia que foi pronunciada em ambos os casos, sendo para o subgrupo CX sem controle de crises (CXR) (p = 0,001) e para o subgrupo CX com controle de crises após a cirurgia (CXB) (p = 0,002). A comparação do volume do hipocampo na RM1 entre os dois subgrupos não revelou diferenças significativas tanto para o hipocampo ipsilateral (p = 0,852) e para o hipocampo contralateral (p = 0,290), afirmando que os pacientes foram igualmente selecionados para a cirurgia. A análise pareada entre os grupos revelou uma diminuição significativa no volume do corpo caloso para o 4 subgrupos
Abstract: Temporal Lobe Epilepsy (TLE) is a condition that is associated to atrophy of the mesial temporal structures as a result of mesial temporal sclerosis (MTS), present in 60 to 70% of patients who undergo surgery. The MTLE associated with MTS has a high degree of resistance to antiepileptic drugs, as a small proportion of individuals can achieve seizure control. Many studies show that the atrophy of the hippocampus contralateral to the epileptogenic focus also undergoes changes. The MR imaging has been a fundamental tool for the diagnosis and quantification of these changes. Thus the study investigate 60 patients, being 30 individuals in drug treatment and 30 in surgical treatment, with the objective of assessing and quantifying these morphological changes found in structures involved in MTLE by means of a software which enables the tracing of the structure; and the association of these volumes with the clinical findings, in order to elucidate on the different responses to medical and surgical treatments. The results shown that the control group had no progression of atrophy of either hippocampus (p > 0.05) or corpus callosum (p = 0.260). The analysis of clinical group identified a reduction in the volume of the hippocampi, both the ipsilateral (affected) and the contralateral in both subgroups, resistant and benign. In relation to the hippocampus ipsilateral there was significant volumetric reduction in the benign group (p = 0.001) and also in the refractory group (p = 0.003). The hippocampus contralateral to the epileptogenic focus in the CLR group presented a significant atrophy (p = 0.001) and the same occurred to CLB (p = 0.011). In the surgery group (SG), the contralateral hippocampus (healthy remnant) showed a progression of atrophy that was pronounced in both the subgroup who continued with seizures after surgery (p = 0.001) and the subgroup who became seizure-free after surgery (p = 0.002). The paired analysis between the subgroups revealed a significant decrease in volume of the corpus callosum for the 4 subgroups
Mestrado
Neurociencias
Mestre em Fisiopatologia Médica
Rissi, Renato 1988. "Alterações musculoesqueléticas em camundongos obesos e desnutridos após protocolo de imobilização articular do membro pélvico unilateral". [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317509.
Texto completoDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: No âmbito da ortopedia, a imobilização articular é um recurso terapêutico eficiente e amplamente utilizado na prática clínica. Apesar de seu uso ser indispensável no tratamento de doenças álgicas ou fraturas, a imobilização ocasiona no paciente uma limitação física temporária de suas habilidades, podendo influenciar em sua locomoção e em suas atividades do cotidiano. A obesidade interfere muitas vezes na relação do hormônio insulina com os mecanismos de síntese e degradação proteica nos músculos. Considerando que a insulina exerce papel fundamental facilitando a síntese e inibindo a proteólise, os pacientes obesos, podem apresentar um balanço negativo no que se diz respeito à formação e degradação da massa muscular em virtude das desordens que estes pacientes geralmente apresentam no perfil insulinêmico. O tecido muscular é a reserva mais importante de proteína disponível no organismo, porém, este tecido se encontra consideravelmente reduzido nos casos de desnutrição proteica. Durante o jejum parcial ou total, a proteína corporal é destruída para proporcionar aminoácidos ao organismo, traduzindo-se desta forma em uma perda de massa corporal total. Quando consideramos a obesidade e a desnutrição proteica, associadas a um paciente imobilizado, a interação dessas condições podem vir a potencializar os prejuízos musculoesqueléticos do paciente. O objetivo deste estudo foi verificar experimentalmente se a condição de imobilização articular potencializa as alterações musculoesqueléticas em animais obesos e desnutridos. Para tal, 60 camundongos da linhagem C57BL6 foram utilizados e divididos em quatro grupos: Controle (GC), Controle Imobilizado (GCI), Obeso Imobilizado (GOI), Desnutrido Imobilizado (GDI). A imobilização articular foi realizada utilizando-se um modelo com esparadrapo/gesso adaptado para uso em camundongos. Os animais permaneceram imobilizados durante 14 dias. A obesidade e a desnutrição proteica foram desenvolvidas por meio de ingestão alimentar de dieta específica para cada grupo. Realizou-se análise da atividade locomotora; quantificação sérica da enzima creatina quinase; análise histomorfométrica da tíbia e dos músculos gastrocnêmio e tibial anterior; determinação do conteúdo de glicogênio intramuscular e zimografia das metaloproteinases (2 e 9). Como resultado, verificou-se a redução da atividade locomotora noturna nos animais imobilizados em relação ao GC; aumento dos níveis séricos da enzima CK nos animais imobilizados em relação ao GC; redução na área e no diâmetro das fibras musculares do gastrocnêmio e tibial anterior nos grupos imobilizados em relação ao GC; diminuição do conteúdo de glicogênio intramuscular no GDI em relação ao GCI; aumento da expressão das metaloproteinases 2 e 9 nos grupos imobilizados em relação ao GC. Portanto, podemos concluir que o protocolo de imobilização articular utilizado é capaz de gerar atrofia musculoesquelética nos animais. Já no caso da interação entre as condições de obesidade/imobilização e desnutrição/imobilização, o tecido musculoesquelético apresenta acréscimo na atrofia, revelando elevado prejuízo muscular nessas condições
Abstract: Within orthopedics, joint immobilization is an effective therapeutic tool and widely used in clinical practice. Although their use is essential in the treatment of painful diseases or fractures, the patient immobilization causes a temporary physical limitation of their abilities and may influence its locomotion and in their daily activities. Obesity often interferes to the hormone insulin in relation with the mechanisms of protein synthesis and degradation in muscle. Considering that insulin plays a key role in facilitating the synthesis and inhibiting proteolysis, obese patients may have a negative balance as regards the formation and degradation of muscle mass because of disorders in these patients insulinemic profile. Muscle tissue is the most important reserve available protein in the body, however, this tissue is considerably reduced in cases of malnutrition. During the partial or total fasting, the body protein is destroyed to provide amino acids to the body, thus translating into a loss of total body mass. When we consider obesity and protein malnutrition associated with an immobilized patient, the interaction of clinical conditions can come to enhance the patient's musculoskeletal damage. The aim of this study was to verify experimentally if the condition of joint immobilization enhances musculoskeletal changes in obese and malnourished animals. To this end, 60 mice C57BL6 were used and divided into four groups: Control (CG), Immobilized Control (ICG), Immobilized obese (IOG), Immobilized Malnourished (IMG). The joint immobilization was performed using a model with tape / plaster adapted for use in mice. The animals remained immobilized for 14 days. Obesity and protein malnutrition were developed by means of specific diets food intake for each group. We performed analysis of locomotor activity; quantification of serum CK; histomorphometric analysis of the tibia and the gastrocnemius and tibialis anterior muscles; determining the content of intramuscular glycogen; zymography of the metalloproteinases (2 and 9). As a result, we found reduction in nocturnal locomotor activity in immobilized animals relative to CG; increased serum levels of creatine kinase in the immobilized animals relative to CG; reduction in the area and diameter of the muscle fibers of the gastrocnemius and tibialis anterior in groups immobilized relative to CG; decreased content of intramuscular glycogen in the group IMG relative to ICG; increased expression of metalloproteinases 2 and 9 in groups immobilized relative to CG. Therefore, we conclude that the joint immobilization protocol used is able to generate skeletal muscle atrophy in animals. In the case of the interaction between the conditions of obesity / immobilization and malnutrition / immobilization, tissue musculoskeletal presents increase in atrophy, revealing high muscle injury in these conditions
Mestrado
Anatomia
Mestre em Biologia Celular e Estrutural
Flôres, Fabíola Niederauer. "Efeitos do sulfato de atropina nos parâmetros hemodinâmicos e hemogasométricos de cães tratados com clorpromazina e dexmedetomidina e anestesiados com isofluorano". Universidade do Estado de Santa Catarina, 2006. http://tede.udesc.br/handle/handle/867.
Texto completoCoordenação de Aperfeiçoamento de Pessoal de Nível Superior
This study was designed to determine the hemodynamic and hemogasometric effects of the premedication with atropine in dogs submitted to chlorpromazine and dexmedetomidine administration under general anesthesia with isoflurane and kept in mechanic ventilation. Six dogs, weighing 17.9 ±3.9kg constituted the two groups of the study, with an interval of seven days between treatments. The animals were instrumentalized using isoflurane, proceeding the catheterization of the dorsal tibial artery and introduction of the SwanGanz catheter through the jugular vein. At the end of the instrumentalization the isoflurane concentration was adjusted to 1 CAM, initiating a 30 minute period of hemodynamic stabilization, when it was measured the parameters for the beginning of the protocol (M -15). It was administered atropine (0,04mg/kg/IM) (group atropine) or NaCl 0.9%/IM (saline group), and then M0 was measured 15 minutes after it. Immediately after this, chlorpromazine (0,5mg/kg) and dexmedetomidine (3μg/kg) were administered intravenously. Five minutes (M5) later all parameters were measured. From this moment, all evaluations were carried through 15 minutes intervals (M20, M35, M50, M65). Data were analyzed one-way ANOVA. Mean comparisons were made by SNK test and t pareado (p≤0,05). Intense bradycardia was observed in saline group and the systolic, diastolic and mean arterial pressure presented higher values in atropine group in relation to the values found in saline group five minutes after chlorpromazine and dexmedetomidine administration, however a lower cardiac index, mainly in M5, was observed in both groups. The total peripheral resistance index was higher in both groups from M5, being much higher and lasting in the atropine group. The left ventricular work index presented a superior value from M0 in atropine group in relation to the saline group. There were statistically significant differences in M20. The mechanical ventilation allowed the ventilatory stability and the hemogasometric parameters had no clinically significant differences. The results allowed concluding that chlorpromazine administration did not brighten up the severe and lasting arterial hypertension produced by the dexmedetomidine. The premedication with atropine kept the stability of the heart rate; however it aggravated the arterial hypertension produced by the alpha-2, increasing the cardiac work and the consumption of oxygen from myocardium
Objetivou-se avaliar os efeitos hemodinâmicos, hemogasométricos e cardiovasculares da prémedicação com atropina em cães tratados com clorpromazina e dexmedetomidina sob anestesia geral com isofluorano e mantidos em ventilação mecânica. Foram utilizados seis cães mestiços, pesando 17,9kg (±3,9), que respeitando-se intervalo de sete dias entre tratamentos, constituíram os dois grupos do estudo. Para instrumentação os animais foram anestesiados com isofluorano, procedendo-se a canulação da artéria tibial dorsal e introdução do cateter de Swan Ganz através da veia jugular direita. Ao término da instrumentação a concentração do isoflurano foi ajustada para 1 CAM, iniciando-se o período de estabilização hemodinâmica de 30 minutos, quando mensurou-se os parâmetros para início do protocolo experimental (M-15). Administrou-se, então, pela via intramuscular, atropina (0,04mg/kg) (grupo atropina) ou cloreto de sódio a 0,9% (grupo salina), após 15 minutos mensurou-se M0, quando subseqüentemente, aplicou-se por via intravenosa, em ambos os grupos, clorpromazina (0,5mg/kg) e dexmedetomidina (3μg/kg). Decorridos cinco minutos (M5) repetiram-se as mensurações. A partir deste momento as avaliações foram realizadas em intervalos de 15 minutos (M20, M35, M50, M65). A análise estatística das médias entre grupos foi realizada através do teste t pareado e a avaliação entre tempo dentro de cada grupo através de ANOVA de 1 via do teste Student Newman Keuls (p≤0,05). Observou-se intensa bradicardia no grupo salina e as pressões arteriais sistólica, diastólica e média apresentaram valores maiores no grupo atropina em relação aos encontrados no grupo salina a partir de M5, porém o índice cardíaco foi reduzido, principalmente em M5, nos dois grupos. No índice de resistência periférica total houve acréscimo a partir de M5 em ambos os grupos, sendo mais acentuado e duradouro no GAtropina. O índice do trabalho ventricular esquerdo apresentou valor superior a partir de M0 no grupo atropina em relação ao grupo salina, sendo a diferença estatisticamente significativa em M20. O controle da ventilação mecânica permitiu a estabilidade ventilatória e os parâmetros hemogasométricos não apresentaram diferença significativa clinicamente. Os resultados permitem concluir que a administração de clorpromazina não amenizou a hipertensão arterial severa e duradoura produzida pela dexmetomidina. A pré medicação com atropina manteve a freqüência cardíaca estável, porém agravou a hipertensão arterial produzida pelo alfa-2, aumentando o trabalho cardíaco e o consumo de oxigênio pelo miocárdio
Sanchez, Anthony. "Implication de la protéine kinase AMP-dépendante dans le contrôle de la masse musculaire : régulation de l’autophagie". Thesis, Montpellier 1, 2012. http://www.theses.fr/2012MON14001/document.
Texto completoSkeletal muscle mass is depending upon a dynamic balance between anabolic and catabolic processes. At a cellular level, two major signaling pathways are involved: the transcription factors FoxO related pathway, implicated in the control of protein breakdown systems(ubiquitin-proteasome system and autophagy), and the IGF-1/Akt/mTORC1 pathway associated with the canonic pathway of protein synthesis. We show in muscle cells that theAMP-activated protein kinase (AMPK) decreases the mTORC1 pathway activity and simulate subiquitin-proteasome and autophagy systems in a FoxO3-dependant manner. Furthermore,we identify Ulk1 as a new interacting partner of AMPK, which plays a major role in the autophagy induction. Moreover, we demonstrate the key role of the eukaryotic translation initiation factor eIF3f in hypertrophy induction and in the associated increase of the mTORC1activity. In addition, we show that the overexpression of an eIF3f mutant resistant to the degradation is associated with a protection against muscle atrophy
Cyphers, Benjamin. "Side Effects of 0.01% Atropine". The Ohio State University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu161701167574429.
Texto completoCollard, Laura. "Rôle du facteur de transcription Srf au cours de l’atrophie du muscle squelettique et dans les cellules satellites". Thesis, Paris 5, 2013. http://www.theses.fr/2013PA05T068/document.
Texto completoAdult skeletal muscle is able to adapt its size to functional demand. It can undergo atrophy or hypertrophy according to mechanical load. To date, the molecules that mediate muscle plasticity remain unclear.Using different models inducing muscle atrophy, we show that the transcription factor Srf is a mediator of mechanotransduction through the actin/Mrtfs/Srf pathway. Mechanical load abolition leads to G-actin nuclear accumulation, delocalization of Mrtf-A, an Srf coactivator, and Srf activity downregulation. This results in a decrease in Srf-dependent transcription. Many Srf target genes encode sarcomeric proteins such as α-skeletal actin, thus a downregulation of Srf-dependent transcription could participate to muscle atrophy. In addition, our results suggest that Srf activity decrease could affect mitochondrial network organization and autophagic flux in a way that remains to be determined. Besides, using a satellite cell-specific conditional and inducible Srf knockout, we show that overload hypertrophy requires Srf expression by satellite cells. Myoblasts proliferation and early differentiation are not altered by Srf loss. However, mutant myoblasts are unable to fuse with myofibers during overload hypertrophy. Altogether, our results demonstrate that Srf is an important player in skeletal muscle plasticity: it is a mediator of mechanotransduction via the actin/Mrtfs/Srf pathway and its expression by satellite cells is required for myoblasts to fuse with myofibers during overload hypertrophy
Guilherme, João Paulo Limongi França. "Efeitos de derivados do composto arylpyrazole (modulador seletivo do receptor de glicocorticóide) sobre a atrofia muscular esquelética". Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/42/42134/tde-30012013-081433/.
Texto completoIn this study, we have tested two new selective modulators named L5 and L7 along with dexamethasone in skeletal muscle structural, functional and molecular aspects. Male Wistar rats were treated with progressive doses of dexamethasone, L5 and L7 for 1 and 7 days. While body weight and food intake were decreased by the dexamethasone treatment in all doses, L5/L7 treatments induced gain in body weight similarly to controls. Muscle weight was decreased by dexamethasone, while L5/L7 were ineffective. Only the dexamethasone treatment caused a decrease in the analyzed cross sectional area of the skeletal muscle fiber types. Soleus tetanic force was decreased by the dexamethasone treatment, while L5/L7 treatments did not alter this parameter. MAFbx/Atrogin-1 and MuRF-1 gene expressions were elevated by dexamethasone; on the other hand, L5/L7 did not modulate any expression of those genes. We conclude that L5/L7, in contrast to dexamethasone, spare skeletal muscle from structural and functional loss, and molecular changes, reinforcing their role as a therapeutic device.
Pereira, Mizael. "Efeitos da suplementação com HMB sobre a musculatura esquelética de ratos submetidos ao tratamento com dexametasona". Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/25/25149/tde-13092016-093443/.
Texto completoThe skeletal muscle is an extremely versatile entity, able to change their patterns and phenotypic characteristics under various conditions such as neuromuscular activity, electrical stimulation, age, hormonal activity and exercise. It is also known that the balance between atrophic and hypertrophic stimuli directly control the muscle mass of the individual and these changes directly affect not only on muscle volume, but also protein content and production strength. In this sense, muscle atrophy (loss of muscle mass) characterized by both, the decrease in cross-sectional area of muscle fibers, but also by decreasing the content of myofibrillar proteins and consequent reduction in muscle volume. This muscle atrophy may occur in various pathological conditions, resulting in decrease or loss of lean body mass leading to a consequent reduction in physical function, quality of life and even worse response to treatment, thus leading to increased mortality. It is clear in that way that the methods aimed at preventing or treating muscle atrophy has important clinical relevance in many groups of patients, as well as being a major contributing factor in the quality of life and autonomy of individuals. Thus, the study of certain treatments that combat muscle atrophy become of vital importance, among which highlight is winning the β-hydroxy-β-methylbutyrate (HMB). Thus, it is aimed in this study to assess the effectiveness of HMB to prevent muscle atrophy induced by dexamethasone (DEXA). For this, we used 32 Wistar animals aged 60 days, distributed in the following groups: experimental group Placebo (GEP), n = 8, treated for 10 consecutive days with gavage and intraperitoneal injection, both containing only saline. Experimental group Dexamethasone (GED), n = 8, treated for 10 consecutive days with gavage containing saline and intraperitoneal injection containing dexamethasone. Experimental group HMB (GEH), n = 8, treated for 10 consecutive days with gavage containing HMB and intraperitoneal injection containing saline solution and Experimental Group Dexamethasone + HMB (GEDH), n = 8, treated for 10 consecutive days with gavage containing HMB and intraperitoneal injection containing DEXA. The animals were placed in collective boxes with 4 animals per cage with food and water at will in a room with 22o temperature and respecting the light / dark 12-hour cycle. Completed the ten days of treatment, the animals were euthanized to collect the material. After the analysis, the mean body weight to groups of animals, muscle weight and values of morphometry were all subjected to one-way ANOVA followed by Tukey test, with the amount considered statistically significant at p <0.05. At the end, it could be concluded that the experimental design applied here, the HMB was not able to mitigate or prevent the loss of body weight induced by DEXA, and the anti-catabolic effect expected by HMB not reflected in the EDL muscle, but was able to prevent atrophy in the soleus muscle.
Vieira, Bruno Hebling. "Brain functional connectivity in regions that exhibit age-related cortical thinning". Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/59/59135/tde-17042018-130342/.
Texto completoO cérebro envelhece, e com isso vêm à tona alterações em sua micro e macroestrutura que se refletem em sua morfologia e funcionamento. Mudanças na estrutura cerebral e acoplamento funcional entre suas regiões podem ser averiguadas através da neuroimagem, e, mais especificamente, imagem por ressonância magnética (IRM). Usando dados de IRM das duas etapas (Pilot and Enhanced) do Nathan Kline Institute Rockland Sample (NKI-RS), totalizando 613 participantes destros, livres de doenças neurodegenerativas, com idade entre 18 e 85 anos, medimos parâmetros de substância cinzenta como volume, espessura, e área de superfície corticais, e também volume de estruturas subcorticais. Também medimos conectividade funcional cortico-cortical, definida como o coeficiente de correlação de Pearson, coeficiente de correlação parcial de Pearson, causalidade instântanea de Granger e causalidade de Granger bivariadas, e coerência parcial direcionada generalizada (GPDC). A GPDC foi medida em cinco frequências entre quatro pares de regiões que demonstraram a mais forte evidência para diminuição da espessura cortical linearmente, medido pela estatística-t associada, e suas alterações ao longo do envelhecimento foram estudadas usando uma abordagem multivariada baseada na Regressão de Dirichlet. Também estudamos associações espaciais entre padrões de alterações morfométricas e na conectividade. Reproduzimos a atrofia generalizada devido à idade reportada na literatura no volume cortical (90% das estruturas estudadas), área de superfície (68%) e espessura (90%), e atrofia volumétrica de várias estruturas subcorticais. Observamos uma associação positiva na distribuição conjunta do valor esperado da espessura cortical aos 18 anos de idade e a redução percentual anual na espessura cortical. Mostramos, ao projetar ambos em seus eixos principais e analizar a distribuição espacial desses índices, que a primeira componente principal correlaciona-se com a granularidade neocortical enquanto que a segunda componente principal representa o tipo cortical. Sobre a conectividade funcional, colhemos evidências para um aumento geral no coeficiente de correlação de Pearson (6% das conexões no Pilot NKI-RS e 2% no Enhanced NKI-RS), com menor proporção de decréscimos (0.1% no Pilot NKI-RS e 0.3% no Enhanced NKI-RS). O coeficiente de correlação parcial de Pearson entre 12 de 65 pares de regiões homotópicas demonstra um padrão de declínio com a idade, sugerindo desconexão inter-hemisférica. No entanto, a causalidade preditiva, como medida através de ambas as métricas de causalidade de Granger, não aparenta o mesmo grau de mudanças observado nas medidas correlacionais. Observamos aumentos na GPDC de várias regiões para si próprias em muitas frequências (25% de um total de 40 auto-conexões), que indica um grau de disconexão às outras regiões. Dadas regiões semente, revelamos padrões significativos espacialmente distribuídos de associação entre efeitos padronizados da idade na conectividade para seus alvos e das espessuras dos alvos. Regiões com menor evidência para o desbastamento relacionado com a idade, como várias áreas occipitais, tendem a ter menos alterações em sua conectividade funcional que regiões com maior evidência suportando o desbastamento cortical relacionado à idade, como diversas regiões frontais. Hipotetizamos que regiões cuja associação é negativa (5% das regiões semente) são parte de sistemas compensatórios, estando correlacionadas com regiões que demonstram os maiores graus de atrofia de modo crescente. Regiões cuja associação é positiva (5%) não teriam mecanismos compensatórios à disposição, e portanto perdem conectividade para regiões atróficas. No geral, encontramos evidências para alterações na conectividade e na morfometria cortical e subcortical no cérebro todo ao longo da extensão da vida adulta humana. Também achamos um padrão específico de associações entre tendências atróficas e alterações na conectividade cerebral devido à idade
Thomaz, Myrian José. "Papel da nefrectomia do rim atrófico nos portadores de hipertensão renovascular". Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5153/tde-29052008-103050/.
Texto completoObjective: to evaluate the beneficial effects of the Nephrectomy of atrophic kidney in patients with renovascular hypertension, on blood pression control and renal function. Methods: retrospective and observational study using data-base of 51 patients with refractory hypertension, atrophic kidney with significant stenosis or complete occlusion of renal artery undergone nephrectomy, between 1989 to 2005.The mean age of 47 ± 15 years (range 13-77 years), the median of serum creatinine level pre-op was 1.3 mg/dl (0.8- 4.5 mg/dl), the median of clearence of creatinine was estimated with MDRD was 54ml/min, the mean systolic blood pressure (BP) pre-op was 149,6± 22,5 mmhg and the mean diastolic BP pre-op was 90,8± 16,7 mmhg with mean 2,8± 1 of antihypertensive medication per day. The blood pressure and serum creatinine were analyzed each year for five years after nephrectomy. Results: The operative mortality was 2%, we found significant decrease of the mean systolic BP from 12 month until 36 month (p<=0,028) and the mean diastolic BP from 12 month until 48 month after nephrectomy (p<=0,045), associated to significant decrease of antihypertensive medication from 12 month to 48 month per patient (p<=0, 05).One year after the procedure, there was decrease of blood pressure in 69% of patients and improve of renal function in 64% of patients. Eight per cent who had worse of renal function after 12 month, recovery the function during the observation period of 60 month. There were no significant differences between \"respondedores\" (good response) and \"não respondedores (bad response)\" after the nephrectomy of the atrophic kidney when we have analyzed age (p=0,89), sex (=0,24), color (p=0,50), co-mobility and risk factors (p>=0,43), level of initial BP, previous serum creatinine (p>=0,90) and the existence of bilateral stenosis (p>=0,74). Eight per cent of patients had end stage of renal disease (ESRD) and dialysis treatment during the study period, all of them with atherosclerotic lesion of renal artery and initial clearence of creatinine less them 25 ml/min. Those patients with fibromuscular dysplasia had better results on the control of BP and renal function them atherosclerotic patients. Conclusion: The take off atrophic kidney caused by obstruction of renal artery is a safe procedure and brings benefits to blood pressure and preserve the renal function, in patients with renovascular hypertension, with better results in those patients with fbromuscular dysplasia
Araujo, de Abreu Paula. "Role of p53 in muscle wasting". Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAJ065/document.
Texto completoMuscle atrophy in cachexia results from the imbalance between protein synthesis and degradation due to activation of the ubiquitin-proteasome pathway. Literature suggests that p53 family members play a role in controlling proliferation, differentiation and death of precursors and muscle fibers. Here we characterize the expression profile of the p53 family members in muscle atrophy in ALS (Amyotrophic Lateral Sclerosis) and in doxorubicin induced cachexia model. We revealed an increased expression of the p53 family members and atrogenes in a correlated manner on both models and a transcriptional activation of Trim63 by p53, p63 and p73. Importantly, we also show that ROS and ceramide accumulation are important for Trim63 induction by doxorubicin. In addition, we tested whether compounds of tocopherol harboring antioxidant activity might reduce muscle atrophy. We showed that this compound counteracts the induction of the Notch pathway, important to muscle development and regeneration
Corlier, Fabian. "Étude de l’imagerie amyloïde cérébrale et de l’élargissement des endosomes dans les cellules sanguines au cours de la maladie d’Alzheimer". Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066687/document.
Texto completoAlzheimer’s disease (AD) diagnostic is based on clinical and biological criteria, and is dependent on impairment of the episodic memory together with a marker of the underlying pathophysiologic process. One of the earliest events in AD pathology in the brain is formation of Amyloid deposits in the extracellular space. One of the main subcellular sites of amyloid-β (Aβ) production from amyloid precursor protein (APP) processing is the endosomal compartment. Appearance of endosomal abnormalities precede the formation of amyloid deposits, in the brain areas affected by disease progression in AD. In the present work we first studied brain amyloid load in patients with posterior cortical atrophy using [11C]PiB ligand retention in positron emitting tomography (PET). In a second part we studied the endosomal compartment in peripheral cells (fibroblasts and mononuclear leucocytes, PBMC) from AD patients, and in lymphoblastoid cell lines (LCL) from Down’s syndrome (DS) individuals where a third copy of amyloid-precursor-protein-coding gene located on chromosome 21 is known to initiate early Alzheimer’s pathology in most DS individuals. Our work shows similar profiles in topography and intensity of [PiB] binding in AD and posterior cortical atrophy (PCA), confirming underlying AD pathology in atypical focal presentations of AD. Analysis of endosomes yielded a significant increase in the frequency of cells with large endosomes in all analyzed cell types, and mean endosome volume correlated to [PiB] binding in PBMC. This result indicates that modifications of the endosomal compartment are seen in the periphery of central nervous system and may represent diagnostic tool from blood
Pham, Minh Tuan. "Analýza změny objemu hipokampu u pacientů s Alzheimerovou chorobou". Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2014. http://www.nusl.cz/ntk/nusl-220871.
Texto completoLoyola, Patricia Resende Alo Nagib. "Comprometimento timico em tres diferentes modelos experimentais de atrofia timica : alterações celulares e de citocinas". [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316963.
Texto completoTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-13T21:07:32Z (GMT). No. of bitstreams: 1 Loyola_PatriciaResendeAloNagib_D.pdf: 6019241 bytes, checksum: 171494f158eff0d6b54b029e9583a35c (MD5) Previous issue date: 2009
Resumo: O timo é o órgão linfóide primário onde os precursores de células T, chamados de timócitos, sofrem processos de diferenciação, seleção e proliferação. Todos estes processos são seqüencialmente dependentes de distintos microambientes no interior do órgão delimitados morfológica e fenotipicamente. Por isso a manutenção do microambiente é essencial para a funcionalidade do órgão. Recentemente, o timo tem sido visto como um órgão alvo de diversas infecções e patologias. No presente trabalho, foi avaliado o comprometimento do timo em três diferentes modelos experimentais capazes de induzir sua atrofia, a saber, infecção experimental pelo fungo P. brasiliensis, infecção experimental por Plasmodium berghei e diabetes induzida quimicamente. Foram avaliadas as subpopulações celulares tímicas, a expressão de citocinas essenciais à maturação dos timócitos e o possível papel do hormônio leptina no estabelecimento e manutenção da atrofia tímica. Sucintamente, os resultados demonstraram que nos três modelos, houve diminuição de celularidade com alterações significativas na freqüência dos subtipos de timócitos, principalmente queda de DP, e menor número de TNCs/animal . No modelo de diabetes além destas alterações, foi detectado a queda dos níveis de leptina, aparentemente, devido á queda da insulina. No modelo de PCM, não houve alteração nos níveis de leptina, entretanto, houve queda na expressão gênica de IL-7 e TGF-ß, fatores timo-estimulantes e inibição da capacidade migratória. Em animais infectados pelo P. berghei, houve queda de leptina e queda na expressão dos genes específicos para IL-7 e TGF-ß, além de aumento na atividade de migração Mediante os dados obtidos em cada modelo, sugere-se que no caso do modelo de PCM a atrofia de grau leve que foi observada deve-se à perda de células por diminuição da expressão das citocinas timo-estimulantes. Em malária acredita-se que a intensa atrofia ocorra por perda da região cortical devido, à queda na expressão das citocinas IL-7, TGF-ß e nos níveis séricos de leptina. Na diabetes induzida, o grau intermediário de atrofia pode ser correlacionado apenas à queda dos níveis séricos de leptina.
Abstract: The thymus is the primary lymphoid organ in which T cell precursors, called thymocytes, undergo processes of differentiation, selection, and proliferation. All these processes are sequentially dependent on distinct thymic microenvironments, which in turn, are delimited morphologically and phenotypically. For these reasons, the maintenance of this microenvironment is crucial for thymus functionality. Recently, the thymus has been seen an organ targeted by several infections and pathologies. In this study, we evaluated thymus compromise under three experimental models capable of inducing atrophy, as follows: (1) experimental infection by the fungus Paracoccidioides brasiliensis (PCM), (2) experimental infection by Plasmodium berghei, and (3) chemically-induced diabetes. We evaluated subpopulations of thymic cells, the expression of cytokines that are essential to thymocyte maturation, and the possible role of the leptin hormone in the establishment of thymic atrophy. Briefly, the results showed that in all three models there was a decrease of cellularity along with significant alterations in the frequency of each thymocyte subtype, especially a decrease in DP, and lower numbers of TNCs per animal. In the diabetes model, besides these alterations, we detected a decrease in leptin levels, apparently related to the insulin drop. In the PCM model, there were no alterations in leptin levels. However, we observed a drop in the expression of IL-7 and TGF- ß, both thymus-stimulant factors, as well as an inhibition of migratory ability. In P. berghei-infected animals there was a drop in leptin as well as in the expression of IL-7 and TGF- ß genes; besides an increase in migration activity. According to the data obtained within each model, we suggest that for the PCM model, the low degree of observed atrophy is a consequence of the loss of cells due to a drop in thymus-stimulant cytokine expression. In malaria, the intense atrophy happens due to the loss of the cortex region, generated by the drop in the expression of IL-7 cytokines, TGF- ß, and seric levels of leptin. As for the induced diabetes, the intermediate degree of atrophy can be correlated only to the drop in seric levels of leptin.
Doutorado
Imunologia
Doutor em Genetica e Biologia Molecular
Sunti, Daniele Martinez de. "Efeitos da abolição da bradicardia reflexa nas respostas cardiorrespiratórias de tambaqui, Colossoma macropomum (Cuvier, 1818), em hipóxia severa: vagotomia versus inibição farmacológica". Universidade Federal de São Carlos, 2013. https://repositorio.ufscar.br/handle/ufscar/1358.
Texto completoUniversidade Federal de Sao Carlos
Hypoxic bradycardia is a reflex response to hypoxia observed in most fish species studied so far. This reflex is initiated by the stimulation of O2 chemoreceptors and induced by an increase in the inhibitory vagal tonus. Despite of being well described and characterized, the hypothesis that hypoxic bradycardia improves the O2 transference from the ventilatory water to the gills still remain to be proved. The utilization of different methods to inhibit hypoxic bradycardia (vagotomy and atropinization) may have contributed to generate different cardiorespiratory responses, making this issue even more controversial. In this study the cardiorespiratory variables (heart frequency fH, metabolic rate - VO2 , O2 extraction from the ventilatory current EO2, gill ventilation - VG , breathing frequency fR, and ventilatory requirement - VG / VO2 ) were measured in the tambaqui, Colossoma macropomum, under normoxia and after 40 min of exposure to severe hypoxia (20 mmHg) and the 3 subsequent hours of recovery. Each fish was subjected to this protocol before (Control group), after atropine administration (A group) and after vagotomy (V group). Under hypoxia the fish of control group displayed the characteristic hypoxic bradycardia (reduction of 56% in fH) with hyperventilation (increases of 96% in fR and 650% in VG ). This hyperventilation was probably responsible by the decrease in EO2 (65%) and, consequently, in the VO2 (62%), resulting in an increase of 1800% in the VG / VO2 . The beginning of the recovery period was characterized by an elevated VO2 (~200% above the normoxic values) accompanied by tachycardia (50.6 bpm) and gradual recovery of EO2, fR, VT and VG . Atropine and vagotomy elevated the fH in normoxia (from 32.0 ± 1.7 to 77.8 ± 4.1 and 80.6 ± 5.8 bpm), indicating a high basal vagal tone. In these two groups the fH remained constant during the experimental time course. This evidenced that the post-hypoxia tachycardia probably occurred as a consequence of a reduction in the cholinergic tonus. The groups control, atropinized and vagotomized did not show significant differences in EO2, VO2 and the other respiratory variables analyzed in any protocol. This results point out that hypoxic bradycardia does not improve the O2 transference to the gills, independently of the method employed to abolish the bradycardic reflex. Therefore, other hypotheses on the hypoxic bradycardia must be investigated in this species.
A bradicardia hipóxica é uma resposta reflexa à hipóxia presente na maioria dos teleósteos. Este reflexo é induzido por um aumento no tônus vagal inibitório e iniciado pela estimulação de quimiorreceptores de oxigênio (O2). Apesar de muito descrita e bem caracterizada, a hipótese de que esta redução na frequência cardíaca (fH) melhore a transferência de O2 pelas brânquias ainda não foi comprovada. A utilização de diferentes métodos para inibir a bradicardia hipóxica (vagotomia e atropinização) pode ter contribuído para gerar respostas cardiorrespiratórias diversas e tornar esta questão ainda mais controversa. Neste trabalho foram avaliadas as variáveis cardiorrespiratórias (fH; taxa metabólica VO2 ; extração de O2 da corrente ventilatória EO2; ventilação branquial VG ; frequência respiratória fR; volume ventilatório VT e necessidade ventilatória VG / VO2 ) do tambaqui, Colossoma macropomum, em normóxia, após 40 min de hipóxia severa (20 mmHg) e durante 3 h de recuperação subsequente. Cada animal foi submetido a este protocolo antes (Ctr), após administração de atropina (A) e após vagotomia (V). Em hipóxia os animais Ctr apresentaram a característica bradicardia hipóxica (redução de 56% na fH) com aumentos na fR (~96 %) e VT (~275 %) elevando muito a VG (~650 %). Esta alta VG , provavelmente foi responsável pela queda significativa na EO2 (65%), consequentemente reduzindo a VO2 (62 %) e aumentando muito a VG / VO2 (1800 %) em hipóxia. O início do período de recuperação do grupo Ctr foi caracterizado por elevada VO2 (~200 % acima dos valores de normóxia), acompanhada de taquicardia (50,6 bpm) e recuperação gradual da EO2, fR, VT e VG . A atropina e a vagotomia elevaram a fH em normóxia (de 32,0 ± 1,7 para 77,8 ± 4,1 e 80,6 ± 5,8 bpm) indicando um alto tônus vagal de repouso, sendo que nestes dois grupos a fH permaneceu constante em todos os tempos experimentais evidenciando que a taquicardia póshipóxia foi, provavelmente, consequência de uma redução no tônus colinérgico. Na EO2, VO2 e demais parâmetros respiratórios analisados não houve diferenças entre os grupos Ctr, A e V, em nenhum momento do protocolo. Estes resultados demonstram que a bradicardia hipóxica, possivelmente, não melhora a transferência de O2 pelas brânquias de tambaqui independente do método de abolição do reflexo bradicárdico. Portanto, outras hipóteses sobre a função da bradicardia hipóxica, como na proteção do miocárdio, devem ser investigadas nesta espécie.
Gurram, Venu. "Preuve de principe pour la thérapie de l'atrophie optique dominante de type1". Thesis, Toulouse 3, 2020. http://www.theses.fr/2020TOU30215.
Texto completoThe impact of visual handicaps has dramatically risen with the contemporary means of visual communication. A major cause of visual impairment lies in optic nerve atrophies often due to defects in mitochondria. Mutations in the gene coding for the mitochondrial protein OPA1 lead to the main form of Dominant Optic Atrophy (DOA), due to degeneration of the Retinal Ganglionic Cells (RGCs), which axons form the optic nerve. OPA1 is involved in the fusion of mitochondria, which together with mitochondrial fission determines the morphology of mitochondria, allows their immediate adaptation to energetic needs and controls their quality by restoring or removing damaged organelles. In addition, OPA1 has other functions including mitochondrial DNA maintenance and protection from apoptosis. To date, there is no therapy available for DOA. My thesis aimed at developing both genetic and pharmacological therapeutic strategies for this disease. Genetic strategy involved the expression of a protein called X from the Borna Disease Virus, which was shown to have neuroprotective properties in in vitro and mouse model of Parkinson Disease by D. Dunia's team. Work in P. Belenguer 's team has shown that X rescued the defects in mitochondrial morphology, dendritic arborisation and synapses induced by downregulation of OPA1 in primarily cultured neurons. In continuation, I showed that X rescued the defects in mitochondrial morphology of fibroblasts of DOA patients harbouring OPA1 mutations by inducing mitochondrial elongation. On the other hand, as part of pharmacological therapy, P. Belenguer's team recently showed that two repurposed drugs, clomiphene and hexestrol, rescued mitochondrial defects in yeast mutated for the orthologue of OPA1. I extended the study to the mammalian system, by analysing the effect of the two drugs on mitochondrial morphology in DOA fibroblasts bearing OPA1 mutations. I showed that the two the drugs rescued defects in mitochondrial morphology by inhibiting the fission process. Although, this project aimed to extend the analysis of the effect of X protein as well as of hexestrol and clomiphene, in vivo, unfortunately, I was not able to evidence the previously described retina and optic nerve defects in a DOA mouse model, impairing its use to test the protective effect of X and the two drugs. In conclusion, although, these pre-clinical studies need to be extended in vivo, the results in vitro indicated that the two genetic and pharmacological strategies could be effective to treat DOA. To my knowledge, this work is first of its kind, where mitochondrial dynamics, i.e. the equilibrium between mitochondrial fusion and fission, was targeted to treat DOA disease. Furthermore, this work is also giving the hope to develop therapies for other RGCs associated mitochondrial diseases like Leber Hereditary Optic Neuropathy and glaucoma
Krug, André Luis de Oliveira. "Papel do exercício resistido na atrofia muscular induzida por dexametasona". Universidade Federal de São Carlos, 2014. https://repositorio.ufscar.br/handle/ufscar/1371.
Texto completoUniversidade Federal de Minas Gerais
The use of glucocorticoids as treatment for allergic and inflammatory conditions has become commom nowadays, although, chronically it can causes many side effects such as peripheral insulin resistance, hyperglycemia and hyperinsulinemia, hypertension, dyslipidemia, body weight loss and muscle atrophy. On the other hand, resistance training (RT) has been recommended as non-pharmacological treatment for some pathological conditions, however little is known about its effects on muscle atrophy induced by chronic treatment with dexamethasone (DEX). The aim of this study was to verify the preventive effect of RT (80% of maximal carrying capacity) on DEX-induced muscle atrophy as well as the responsible mechanisms for this response. Forty-three wistar rats (200-250g) were allocated into four groups: sedentary control (SC), sedentary treated with DEX (SD), trained control (TC) and trained treated with DEX (TD). After a familiarization period on the ladder, a maximal voluntary carrying capacity test (MVCC) was performed to determinate the training intensity and the rats underwent or RT (80% MCCT, 4 days/week, 70 days) or remained sedentary. The MVCC was performed in the beginning, after 4 weeks, before and after the DEX treatment. Through the last ten days, the animals received DEX (0.5 mg/kg/day, i.p.) or saline solution. After 24 hours of the last training session, the animals were euthanized and the flexor hallucis longus (FHL), tibialis anterior (TA) and soleus (SOL) muscles were collected and weighted for further analysis of mTOR, p70S6K, FOXO3a, Atrogin-1 and MuRF-1 protein levels. The results were presented as mean ± SEM, α<0.05. DEX treatment evoked adrenal gland atrophy (-47%), body weight loss (-21%) and food intake reduction (-28%). The RT increased MVCC of trained animals (+215%). Also, DEX treatment reduced FHL and TA muscles mass (-19.6% e -17.7%, respectively), which was associated with the MuRF-1 protein level increase (+37% e +45,5%, respectively). We did not observe any alterations in mTOR, p70S6K, FOXO3a and Atrogin-1 protein levels after DEX treatment. RT was be able to attenuate FHL muscle atrophy due to blockade of MuRF-1 increase (-3.5%). In addition, it did increase mTOR (+63% for TC e TD) e p70S6K (+46% and +49% for TC e TD, respectively) protein levels in FHL muscle. FOXO3a and Atrogin-1 protein levels were not altered by RT. SOL muscle was not affected by neither treatment nor training. Therefore, these results allow us to suggest that DEX-induced muscle atrophy observed in the FHL and TA muscles can be associated with increases in MuRF-1 protein level. RT-induced attenuation of FHL muscle atrophy involved increases in mTOR and p70S6K protein levels associated with maintenance of MuRF-1 protein levels.
O uso de glicocorticoides como tratamento de quadros inflamatórios e alérgicos tem sido uma constante na atualidade, embora, cronicamente provoque vários efeitos colaterais como resistência periférica à insulina, hiperglicemia e hiperinsulinemia, hipertensão, dislipidemia, perda de peso corporal e atrofia muscular. Por outro lado o treinamento resistido (TR) tem sido recomendado como tratamento não farmacológico em alguns estados patológicos, embora pouco se conheça sobre seus efeitos sobre a atrofia muscular induzida pelo tratamento crônico com dexametasona (DEX). O objetivo principal deste trabalho foi verificar o efeito preventivo do TR a 80% do carregamento máximo sobre a atrofia muscular induzida pela DEX, bem como os mecanismos responsáveis por esta resposta. Foram utilizados 43 ratos Wistar (200-250g) distribuídos em 4 grupos: sedentário controle (SC), sedentário tratado com DEX (SD), treinado controle (TC) e treinado tratado com DEX (TD). Após um período de adaptação na escada, foi realizado um teste de carregamento máximo (TCM) para determinação da intensidade do treino. Em seguida, os ratos foram submetidos ao treinamento resistido (80% da capacidade máxima, 4 dias/semana, 70 dias) ou mantidos sedentários. Os TCM foram realizados no início do protocolo experimental, após 4 semanas, antes e após o tratamento com DEX. Nos últimos 10 dias, os animais receberam DEX (0,5 mg/kg por dia, i.p.) ou solução salina. Após 24 horas da última sessão de exercício, os animais foram eutanasiados e os músculos flexor longo do hálux (FHL), tibial anterior (TA) e sóleo (SOL) foram coletados, pesados e seus valores normalizados pelo tamanho da tíbia. Analisamos a produção das proteínas mTOR, p70S6K, FOXO3a, Atrogina-1 e MuRF-1. Os resultados são apresentados como média ± EPM, α<0,05. A DEX provocou redução do peso da glândula adrenal (-47%), peso corporal (-21%) e ingestão alimentar (- 28%). O TR aumentou a capacidade física dos animais treinados (+215%). O tratamento com DEX reduziu a massa muscular do FHL e TA (-19,6% e -17,7%, respectivamente), que foi associada ao aumento da proteína MuRF-1 (+37% e +45,5%, respectivamente), não foram observadas alterações nas proteínas mTOR, p70S6K, FOXO3a e Atrogina-1 após o tratamento com DEX. O TR foi capaz de atenuar a atrofia no músculo FHL, pois conseguiu bloquear o aumento da proteína MuRF-1 (-3,5%), além de aumentar os níveis de mTOR (+63% para TC e TD) e p70S6K (+46% e +49% para TC e TD, respectivamente), embora não tenha alterado os valores de FOXO3a e Atrogina-1. O músculo SOL não foi alterado nem pelo tratamento nem pelo treinamento. Portanto, os resultados obtidos até o presente momento permite-nos sugerir que a atrofia observada nos músculos TA e FHL causadas por 10 dias de tratamento com DEX pode estar associada ao aumento da proteína MuRF-1. Por sua vez, o TR foi capaz de prevenir a atrofia no músculo FHL em decorrência do aumento de mTOR e p70S6K somados a manutenção dos valores de MuRF-1.
Souza, Soraia Figueiredo de [UNESP]. "Reabilitação em cães com atrofia muscular induzida". Universidade Estadual Paulista (UNESP), 2010. http://hdl.handle.net/11449/101099.
Texto completoConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Avaliou-se a resposta de diferentes protocolos fisioterapêuticos em cães após a indução de atrofia muscular por meio da imobilização do joelho por 30 dias. Os grupos foram denominados grupo C ou controle, grupo M (massagem e movimentação passiva), grupo E (massagem, movimentação passiva e eletroterapia), grupo H (massagem, movimentação passiva e hidroterapia em esteira aquática) e grupo EH (massagem, movimentação passiva, eletroterapia e hidroterapia em esteira aquática). Foram mensurados, os graus de claudicação, amplitude articular, circunferência da coxa, variação sérica das enzimas creatina-quinase e lactato-desidrogenase, bem como a morfometria muscular das fibras de contração rápida e contração lenta do músculo vasto lateral marcadas pela técnica de imunoistoquímica. Os cães do grupo H apresentaram retorno mais precoce à função do membro pélvico direito, mostrando que a hidroterapia pode ser beneficamente empregada para a recuperação em cães claudicantes. A fisioterapia reduziu a contratura articular. Verificou-se maior recuperação da área transversal das fibras musculares de contração lenta e rápida nos cães submetidos à eletroterapia aos 60 dias de pós-operatório. De acordo com os resultados encontrados, foi possível concluir que as modalidades terapêuticas de massagem, movimentação passiva da articulação, estimulação elétrica neuromuscular e hidroterapia por caminhada em esteira aquática aceleram a recuperação clínica em cães com atrofia muscular induzida
The response to different physiotherapeutic protocols was evaluated in dogs with muscle atrophy induced by a 30-day-long immobilization of the stifle joint. The animals were divided in groups namely: C (control), M (massage and passive range of motion), E (massage, passive range of motion and neuromuscular electrical stimulation), H (massage, passive range of motion and hydrotherapy in underwater treadmill), and EH group (massage, passive range of motion, neuromuscular electrical stimulation and hydrotherapy in underwater treadmill). The degree of lameness, range motion, thigh circumference, range of serum creatine kinase (CK) and lactate dehydrogenase (LDH) were then evaluated, as well as the morphometry of fast- and slow-twitch muscle fibers of the vastus lateralis by immunohistochemistry. Group H dogs regained function of the right hind limb faster than the other groups. This result shows that hydrotherapy helped in the recovery process of lame dogs. Physiotherapy reduced the joint contracture. There was a higher recovery rate of cross-sectional area of slow-twitch and fast-twitch muscle fibers and thigh circumference in dogs submitted to neuromuscular electrical stimulation at 60 days post-surgery. According to these results, it was possible to conclude that therapeutics modalities such as massage, passive range of motion of the joint, neuromuscular electrical stimulation and hydrotherapy by walking on underwater treadmill accelerate clinical recovery in dogs with induced muscle atrophy
Gameiro, Jacy. "Aterações no microambiente timico frente a diferentes agentes indutores de atrofia". [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316964.
Texto completoTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: O timo é o órgão linfóide primário responsável pelo amadurecimento dos linfócitos T. O processo de maturação é dependente da integridade do microambiente e da migração coordenada por elementos de matriz e quimiocinas dos precursores hematopoiéticos nos distintos nichos tímicos. Entretanto, a literatura mostra que profundas alterações no microambiente tímico, e conseqüentemente no desenvolvimento e amadurecimento dos linfócitos T, podem ocorrer como resultado de algumas patologias. No presente trabalho, analisamos a indução de atrofia e as alterações no microambiente tímico frente a três diferentes agentes indutores de atrofia, sendo dois agentes patogênicos, P.brasiliensis e P.berghei e uma doença metabólica, a diabetes induzida por aloxana. Nos três modelos estudados foi observada a atrofia do órgão com diferente intensidade nas alterações de componentes do microambiente tímico. Importantes moléculas associadas com a migração intratímica mostraram-se alteradas com modificações significativas nos elementos de matriz e nas quimiocinas bem como na expressão dos seus respectivos receptores. Ainda, a migração ex vivo também se mostrou alterada na atrofia induzida pelos agentes patogênicos, mas não no modelo de atrofia induzido por aloxana, sugerindo que as alterações desencadeadas são específicas de cada condição patológica analisada. As modificações nos elementos estudados sugerem alterações no padrão de migração intratímica e na exportação de timócitos, com comprometimento da função tímica, levando a maturação desequilibrada dos timócitos, com conseqüências para a resposta imune periférica.
Abstract: Thymus is the primary lymphoid organ responsible for differentiation of Tlymphocytes. This process is dependent of thymic microenvironment integrity and coordinated migration of hematopoietic precursors by chemokines and extracellular matrix elements. However, the literature shows that deep alterations in thymus microenvironment with modifications in thymocyte development may occur such as result of some pathological disorders. In this study we analyzed the atrophy induction and alterations in thymic microenvironment in three different models of thymus atrophy. We studied two models of infectious diseases, P.brasiliensis and P.berghei, and a metabolic disorder, alloxan induced diabetes. We have observed thymus atrophy in all models with different alterations levels in thymus microenvironment elements. Important molecules associated with intrathymic migration were been altered with significant modifications in extracellular matrix elements, chemokines and their specific receptors. Besides, ex vivo migration was altered in thymus atrophy induced by pathogenic agents, but no alterations were observed in diabetic mice suggesting that different pathological conditions studied, leads to singular alterations in thymus compartment. The modifications in thymic molecules observed in our models, suggest impaired thymus functionality and alterations in thymocyte migration patterns These alterations can lead T cell maturation imbalance with consequences in Tlymphocyte immune response.
Doutorado
Imunologia
Doutor em Genetica e Biologia Molecular
Francelin, Carolina 1985. "Estudo dos compartimentos linfóide e estromal do microambiente tímico em camundongos com diabetes experimentalmente induzido pelo Aloxana = Study of lymphoid and stromal compartiments of the thymic microenvironment in experimentally induced diabetes". [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316962.
Texto completoTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: O timo é o órgão linfoide primário responsável pela geração de linfócitos T maduros. Para que isso ocorra, células precursoras de linfócitos T, provenientes da medula óssea, entram no timo e migram constantemente através do microambiente tímico ¿ o qual é composto por componentes linfoides e não linfoides. Esta migração intratímica é fundamental para que os precursores das células T encontrem os sinais necessários para sobrevivência, proliferação, diferenciação e geração de diversidade de repertório. Assim como os outros órgãos linfoides, o timo está sujeito a um rígido controle neuroendócrino, o qual impõe consequências diretas sobre o funcionamento do sistema imunológico através de neurotransmissores, hormônios e citocinas. Entretanto, ainda é pouco o que se sabe sobre as interações entre os componentes do timo e hormônios do eixo HPA. Neste trabalho, foram avaliados os compartimentos linfoide e estromal na atrofia tímica observada no modelo experimental da diabetes tipo I. Nesse estudo foi observado que camundongos diabéticos apresentaram redução nos níveis séricos e intratímicos de leptina e elevados níveis séricos e intratímicos de corticosteroide, acompanhando a queda dos níveis séricos de insulina. Diante das alterações hormonais, nós observamos: modificações nos componentes linfoides e estromais do timo, caracterizadas por redução no número de timócitos, aumento na secreção de elementos de matriz extracelular, contração da porção cortical do timo acompanhada por acúmulo de linfócitos no estágio pré - seleção positiva, aumento da apoptose de células epiteliais tímicas e timócitos e aumento na exportação de células T imaturas para os órgãos linfoides secundários. Sucintamente, após o estabelecimento da hiperglicemia e ausência de insulina circulante, o timo de animais diabéticos apresentou alterações morfológicas e em todos os tipos celulares e fatores solúveis que compõe o estroma tímico, culminando em alterações nas células presentes na periferia do sistema imune. Acreditamos que os dados gerados nesse estudo contribuem, s.m.j., para um melhor entendimento da deficiência na resposta imune em indivíduos diabéticos e do desenvolvimento do linfócito T na ausência de insulina
Abstract: Thymus is the primary lymphoid organ responsible for the generation of T lymphocytes. For this to occur, precursor cells of T lymphocytes from bone marrow enter the thymus and migrate continuously through the thymic microenvironment - which consists of lymphoid and non-lymphoid components. This intrathymic migration is essential for T cell precursors get contact with signs that promote survival, proliferation, differentiation and generation of diversity of repertoire. Like other lymphoid organs, the thymus is subject to a rigid neuro-endocrine control, which requires direct consequences on the functioning of the immune system through neurotransmitters, hormones and cytokines. However, it is still little known about the interactions between the components of thymus hormones and the HPA axis. In this study, we evaluated the alterations in lymphoid and stromal thymic compartiments in thymic atrophy during experimental model of diabetes type I. Here in, we found that diabetic mice exhibit a reduction in serum aand intrathymic levels of leptin yet, intrathymic and serum corticosteroid levels were high, followed by a drop in serum insulin levels. Given the hormonal changes, we observed: changes in lymphoid and non-lymphoid component of the thymus, characterized by reduction in the number of thymocytes, increased secretion of extracellular matrix elements, contraction of the cortical portion of the thymus accompanied by accumulation of lymphocytes in the pre stage - positive selection, increased apoptosis of thymic epithelial cells and thymocytes and increase in export of immature T cells to secondary lymphoid organs. Briefly, after the onset of hyperglycemia and lack of circulating insulin, thymus in diabetic animals showed alterations in all cell types that comprise the thymic microenvironment, resulting in abnormal cells present in the periphery of the immune system. We believe that the data generated in this study will contribute to a better understanding of the immune deficiency in diabetic individuals and the development of T lymphocytes in the absence of insulin response
Doutorado
Imunologia
Doutora em Genética e Biologia Molecular
Ramos, Gracielle Vieira. "Efeito do hormônio tireoidiano (T3) sobre a expressão da E3 ligase Mdm2 e suas implicações na regulação do trofismo muscular". Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/42/42134/tde-19112014-154918/.
Texto completoPrevious studies in our lab through microarray assay observed Mdm2, an E3 ligase, up regulated in soleus muscle from hyperthyroid rats. In this sense, we inferred that Mdm2 could be related to muscle atrophy caused by T3. To test our hypothesis, rats were induced to experimental hyperthyroidism for subsequent analysis. Along the muscle mass loss, the increase on Mdm2 gene expression was confirmed (p<0.05) as well as protein expression by RT-PCR and Western Blot, respectively. Interestingly, Mdm2 was expressed predominantly in fiber I type during T3 treatment, demonstrating a higher sensibility when compared to type II fiber. Moreover, it was observed a severe decrease in Pax7/MyoD labeling, associated to an increase on Mdm2 labeling, suggesting that T3 could be associated with inactivation of satellite cells. Surprisingly, Mdm2 inhibition in myotubes have induced severe decrease on myotubes diameter (~35%, p<0.05), in other words, Mdm2 inhibition was not able to decrease muscle proteolysis during high levels of T3. Thus, the increase on Mdm2 levels could be a compensatory effect to reduce the muscle mass loss during T3 treatment. This conclusion is highlighted by the myotubes atrophy observed during the Mdm2 inhibition without T3 treatment.
Silva, Willian das Neves. "Efeitos do treinamento de força no músculo esquelético em ratos com caquexia induzida pelo câncer". Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/39/39132/tde-10062016-100708/.
Texto completoThe lack of therapies for cachexia is a key problem in cancer treatment. In contrast, resistance exercise training (RET) has been adopted as nonpharmacological anti-catabolic strategy, preventing muscle wasting and muscle dysfunction. However, the role of RET to counteract cancer cachexia is still speculative. Presently, we test whether RET would counteract skeletal muscle wasting in a severe cancer cachexia rat model. Methods: Male Wistar rats were randomly assigned into four experimental groups; 1) untrained control rats injected with saline solution in the bone marrow (control), 2) rats injected with saline solution in the bone marrow and submitted to RET (control + RET), 3) untrained rats injected with Walker 256 tumor cells in the bone marrow (tumor) and 4) rats injected with Walker 256 tumor cells in the bone marrow and submitted to RET (tumor + RET). Skeletal muscle mass and fiber cross sectional area, markers of metabolic and protein turnover impairment, in vivo and ex vivo skeletal muscle function, food intake, tumor growth and mortality rate were assessed. Results: Tumor group displayed skeletal muscle atrophy fifteen days post tumor cells injection as assessed by Plantaris (-20.5%) and EDL (-20.0%) muscle mass. EDL atrophy was confirmed by histological analysis, showing 43.8% decline in the fiber cross sectional area. Even though RET increased the lactate dehydrogenase protein content and fully restored phosphorylated form of 4EBP-1 (i.e. a repressor of mRNA translation) to the control levels in skeletal muscle, it failed to rescue muscle morphology in tumorbearing rats. Indeed, RET has not mitigated loss of muscle function, anorexia, tumor growth or mortality rate. However, loss of strength capacity (assessed by 1-RM test performance) demonstrated a negative correlation with rats´ survival (p = 0.02), suggesting that loss of strength capacity predicts cancer mortality. Conclusions: Bone marrow injection of Walker 256 tumor cells in rats induces cancer cachexia. RET is ineffective to mitigate cancer-induced skeletal muscle wasting in this rat model. However, strength capacity predicts cancer survival, suggesting that new studies are needed to elucidate the putative therapeutic role of different exercise training regimens in counteracting cancer cachexia and tumor progression
Welling, Leonardo Christiaan. "Estudo prospectivo sobre os resultados estéticos, funcionais e clínicos da craniotomia minipterional em comparação com a craniotomia pterional clássica". Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5138/tde-14102013-115952/.
Texto completoIntroduction: The pterional approach is one of the most commonly used craniotomy. However it has disadvantages, such as complete dissection of the temporalis muscle. This may lead to muscular atrophy and facial deformity. The minipterional craniotomy was described in 2007 and the anatomic exposure provided by the pterional and minipterional approaches were similar in the total area of exposure and angular view. Objectives: This prospective randomized study was designed to compare the clinical, functional and aesthetic results of two surgical techniques for microsurgical clipping of anterior circulation aneurysms. Methods: Overall, 58 eligible patients admitted with ruptured and unruptured anterior circulation aneurysms were enrolled in the study. In group A, 28 patients were operated with the minipterional technique. In Group B 30 patients were operated according to the classical pterional craniotomy. Patients with intracranial haematomas, ophthalmic aneurysms and giant aneurysms were excluded. The aesthetic results were analyzed with 2 methods. In the first, the patients were showed to a rule, with a scale from 0 to 100, in which 0 mean the best result and 100 the worst result. Photos were taken and showed to two independent observers, the results were classified as excellent, good, regular or poor, according to a pre-determined scale. The degree of atrophy was measured with three methods. In the first one, the authors observed the percentage of thick reduction in the temporal muscle, subcutaneous tissue and skin. In the second method the percentage of thick reduction of the isolated temporal muscle was observed and the third the volumetric analysis of the temporal muscle, subcutaneous tissue and skin was calculated from the superior edge of zygomatic arch to superior temporal line using the OsiriX software (OsiriX - Pixmeo Sarl Geneva/Suíça). The functional results were compared using the Modified Rankin Score. Others variables such frontal facial palsy, post-operative hemorrhage, cerebrospinal fistulas, hydrocephalus and mortality were also analyzed. Results: In both groups the demographic and pre-operative characteristics were similar. The satisfaction with aesthetic results were observed in 79% (19) in group A and 52% (13) in group B (p=0,07). The mean value observed in the rule was 27 in group A and 45,8 in group B (p=0,03). When patients classified as Rankin Modified Score of 0 or 1 only were included the mean value observed in the rule was 25,2 in group A and 39,4 in group B (p=0,11). Two independent observers analyzed the patients photos and the kappa coefficient correlation for the aesthetic results was 0,73. According to them excellent and good results were observed in 87% (21) in minipterional group and 48% (12) in the pterional group. The degree of atrophy of temporal muscle, subcutaneous tissue and skin (method 1) was14,9% in group A and 24,3% in group B (p=0,01). The measurement of temporal muscle (method 2) revealed that the degree of atrophy was 12,7% in group A and 22% in group B (p=0,005). The volumetric reduction of the structures (method 3) was 14,8% in group A and 24,5% in group B (p=0,012). Rankin Modified Score was similar in both groups in the 6-month evaluation (p=0,99). Mortality occurred in 4 patients in group A and 5 patients in group B (p=1,0). Conclusion: These clinical results indicate that the minipterional is a safe procedure. We can estimate the better cosmetic results with less facial contour deformity since the percentage of thick and volumetric reduction in temporal muscle, subcutaneous tissue and skin were demonstrated. It can be an excellent and better alternative to the classical pterional approach
Arnould, David. "Reconditionnement musculaire dans un modèle murin de myopathie centronucléaire autosomique dominante par inactivation du gène myostatine". Thesis, Lyon, 2018. http://www.theses.fr/2018LYSES008/document.
Texto completoAutosomal dominant centronuclear myopathy (AD-CNM) is a rare congenital muscle disease caused by mutations predominantly found in the dynamin 2 gene (DNM2). The clinical features generally reported are progressive muscle atrophy and weakness. To date, no treatment is available. The mouse model for AD-CNM harboring a mutation of the dynamin-2 gene (KI-Dnm2R465W/+) reproduces some of the human clinical features, notably muscle atrophy and weakness. Mstn, is a master negative regulator of skeletal muscle mass. We hypothesized that inactivation of mstn could limit muscle atrophy and weakness reported in the AD-CNM mouse model (KI-dnm2R465W/+). To test this hypothesis, we intercrossed KI-Dnm2R465W/+ mice with mice inactivated for mstn (KO-mstn) to generate a double mutated lineage (KIKO). The present study demonstrates that mstn gene inactivation allows for an improvement of muscle weight and volume, prevents muscle weakness and motor skill alterations. Our data also reveal that inactivation of mstn essentially downregulates some actors implicated in the catabolic ubiquitin-proteasome system. Furthermore, we show that inactivation of mstn decreases the frequency of of histological abnormalities characteristical in KI mice. We hypothesize that these abnormalities could be due to an alteration of mitochondrial function and network. The perspective to this work is to verify this hypothesis in the mouse model, which will contribute to a better understanding of the physiopathological mechanisms and can open new insight in the therapeutical approach to AD-CNM
Bocca, Cinzia isabelle. "OPA1 et atrophie optique dominante : étude physiopathologique par approche métabolomique et lipidomique". Thesis, Angers, 2018. http://www.theses.fr/2018ANGE0059.
Texto completoDominant Optic Atrophy (DOA, MIM #165500) is an inherited disease affecting one of 30,000 individuals. It mostly affects the retinal ganglion cells that make up the optic nerve, leading to the decrease invisual acuity. This genetically and clinically heterogeneous pathology is mainly related to the mutations on OPA1 gene. The mitochondrial protein OPA1 has been implicated in many functions including mitochondrial fusion, energy metabolism, apoptosis and maintenance of mitochondrial DNA. In order to investigate the overall effects of OPA1 dysfunctions, we developed non-targeted metabolomic and lipidomic approaches on patients' plasmas and fibroblasts as well as on OPA1 knock-out mouse fibroblast model. Despite the specificities of each model and matrix, we clearly revealed a common metabolic alteration including an aspartate deficiency due to the energy defect observed in all our models and responsible for the alteration of nucleotide metabolism. With a lipidomic approach, we revealed in the knock-out cell model a huge increase of triglycerides which is related to the energetic deficiency. Moreover, we highlighted a major alteration on phospholipids, testifying a deep remodeling of mitochondrial membrane structures. Taken together, our analysis revealed new pathophysiological roles of OPA1. Finally, our work opens new perspectives to improve the diagnosis and the patient care
Nowak, Deborah J. "Spinal muscular atrophy /". Online version of thesis, 1995. http://hdl.handle.net/1850/12227.
Texto completoMitchell, Christopher Paul. "Atrophy for Orchestra". OpenSIUC, 2012. https://opensiuc.lib.siu.edu/theses/913.
Texto completoLecomte, Virginie. "Rôle des facteurs de transcription SREBP-1 dans la fonction musculaire : implication des répresseurs transcriptionnels BHLHB2 et BHLHB3". Phd thesis, Université Claude Bernard - Lyon I, 2009. http://tel.archives-ouvertes.fr/tel-00583077.
Texto completoMartins, Carlos Eduardo Carvalho. "Efeitos da suplementação de leucina e do treinamento de força sobre a miopatia diabética em modelo experimental de diabetes mellitus induzido por estreptozotocina". Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/9/9132/tde-04072016-094630/.
Texto completoIn this study, we evaluated the effects of chronic supplementation with leucine and resistance training on diabetic myopathy. 40 Wistar Hannover rats were divided into 5 groups: control, non-diabetic (C), untreated diabetic (D), trained diabetic (DT), diabetic supplemented with leucine and trained (DLT). The beginning of the interventions occurred in the 4th week of life of the animals, and lasted for 8 weeks. Were evaluated: body weight, food and water intake, blood concentrations of glucose, insulin and lipid profile; voluntary muscle functional capacity through grip strength and ambulation test; intracellular content of proteins related to the anabolic mTOR and p70S6K pathway, total and phosphorylated in the extensor digitorum longus muscle. Diabetics untreated mice (group D) had hyperglycemia and moderate hypoinsulinemia, lower body mass, food and water intake, reduced absolute weights of the muscles of the long extensor digitorum, and gastrocnemius, the lower grip strength, lower ambulation capacity and lower activity of mTOR and p70S6K protein compared the C group, featuring diabetic myopathy. The relative weight of the gastrocnemius muscle (absolute weight / 100g of body weight) was greater in DT and DLT groups compared with group D, and higher in the DLT group compared to the DL group (P < 0.05). No statistical difference between the DL and D groups on the relative weights of the muscles, that is, chronic supplementation of leucine did not affect this parameter in diabetic rats. Interestingly, there was statistical difference between the DL and D groups on muscle strength (P < 0.05), with no difference between groups DL and C on the blood glucose; that is, the diet supplemented with leucine was able to control glycemia and avoid loss of muscle strength of diabetic animals. Resistance training also controlled glycemia, recovered muscle strength and improved the capacity of ambulation of diabetic animals and the regulation of the mTOR-p70S6K pathway. The phosphorylation of mTOR-p70S6K pathway was higher only in the DT and DLT groups compared with the D group (P < 0.05), and no difference between the DT and C groups, suggesting that the training recovered muscle mass in diabetic animals. Total cholesterol was greater in Group D compared to the group C; and trained diabetic groups (DLT and DT), this parameter was lower than that of the D group (P < 0.05). In addition, HDL-C increased in trained groups (DT and DLT) as compared to group D, but had no effect the group that received only leucine supplementation (DL group). Therefore, in this study, chronic supplementation of leucine alone normalized glucose and improved muscle strength of diabetic animals. In addition, resistance training was responsible for the largest increase in strength and muscle mass, as well as the normalization of glucose, elevated concentrations of HDL-C and reduction in total cholesterol of animals diabetics and both were able to recover mTOR- p70S6K pathway.
Worschech, Adriana. "Atrofia parcial em biopsias de agulha de prostata : Util no diagnostico diferencial entre carcinoma e atrofia da prostata?" [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308445.
Texto completoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: A atrofia parcial (AP) é uma lesão benigna que mais freqüentemente imita adenocarcinoma, particularmente a variante parcial. AP ocorre com maior freqüência no lobo posterior ou zona periférica e ganhou importância maior com o uso das biópsias por agulha na detecção do carcinoma prostático. A atrofia parcial e a hiperplasia pós-atrófica (atrofia hiperplásica) são as lesões benignas que mais freqüentemente são confundidas com adenocarcinoma. Uma das razões que contribuem para dificultar o diagnóstico da atrofia parcial está relacionada com a ausência de células basais em alguns ácinos. Mais recentemente a aplicação da molécula de AMACR (alfa-metilacil Co-enzima A racemase) como marcador de células neoplásicas através de imunoistoquímica tem auxiliado no diagnóstico diferencial com o adenocarcinoma. Entretanto, sua aplicação na rotina diagnóstica ainda não está estabelecida. A imunoexpressão da AMACR pode causar algumas dúvidas em sua interpretação. Na literatura existem poucos estudos que relatam a expressão da AMACR em atrofia parcial. Avaliamos através da imunoistoquímica a expressão da AMACR e do 34ßE12 (citoqueratina de alto peso molecular) através do coquetel P504S+34ßE12 em material proveniente de 74 biópsias por agulha de próstata correspondendo a 61 pacientes. Foram analisados um total de 1198 ácinos prostáticos (324 ácinos com adenocarcinoma, 213 ácinos normais, 190 ácinos com atrofia parcial, 298 ácinos com hiperplasia pós-atrófica, 139 ácinos com atrofia simples e 34 ácinos com atrofia esclerosante). Nos ácinos com adenocarcinoma a intensidade da marcação da AMACR foi forte em 251/324 (77.5%) e fraca 73/324 (22.5%). Não houveram casos negativos. Nos ácinos normais observou-se marcação para a AMACR forte em 13/213 (6.1%), fraca em 33/213 (15.5%) e negativa em 167/213 (78.4%). A atrofia parcial apresentou marcação para a AMACR fraca em 47/190 (24.7%) e negativa em 143/190 (75.3%). Não houve marcação forte em nenhum dos casos de atrofia parcial. Os ácinos normais mostraram expressão para AMACR negativo, fraco e forte onde os valores foram respectivamente 167/213 (78,4%), 33/213 (15,5%) e 13/213 (6,1%). A atrofia parcial mostrou-se negativa, e fraca para imunoexpressão da AMACR em 143/190 (75,3%) e 47/190 (24,7%) respectivamente. Não foi observada forte positividade em atrofia parcial, no entanto, a fraca positividade observada em cerca de 25% dos ácinos pode causar dificuldade para a interpretação correta no diagnóstico diferencial de câncer e atrofia parcial. A AMACR foi negativa em todos os ácinos da atrofia simples, hiperplásica (ou hiperplasia pós-atrófica) e esclerosante, por conseguinte, sem qualquer ajuda no diagnóstico diferencial de adenocar-cinoma. A distribuição das células basais, observadas na atrofia simples, hiperplásica e esclerosante foram descontínuas e as células do compartimento secretor mostraram imunoexpressão aberrante de 34ßE12 sugerindo um fenótipo intermédio. Analisando-se os estes resultados conclui-se que o diagnóstico diferencial do adenocarcinoma com atrofia parcial deve ser feito com cautela considerando-se que a expressão da AMACR, apesar de fraca em nosso estudo, pode ocorrer em cerca de 25% dos ácinos. Soma-se a este achado o fato de que em 23.2% dos ácinos de atrofia parcial as células basais estão ausentes. Estes dados impõem cautela no difícil diagnóstico diferencial de pequenos focos "suspeitos, mas não diagnósticos de adenocarcinoma da próstata", sendo que, em alguns casos, os critérios puramente morfológicos poderão ser os únicos na identificação da lesão.
Abstract: Prostatic atrophy (PA) is the benign lesion that most frequently mimicks adenocarcinoma particularly the partial variant. PA occurs more frequently in the peripheral zone and gained greater importance with the use of needle biopsies in detecting cancer of the prostate. Partial atrophy and post-atrophic hyperplasia (hyperplastic atrophy) are the benign lesions that most often are confused with adenocarcinoma. One of the reasons that contribute to make the diagnosis of partial atrophy difficult is related to the absence of basal cell in some acini. More recently the application of AMACR (alpha-metilacil Co-enzyme A racemase) as a marker of malignant cells through immunohistochemistry has helped in the differential diagnosis with prostate cancer. However, its application in routine diagnosis is not yet established. The immunoexpression of AMACR may cause some doubt in interpretation. In literature there are few studies that reported the expression of AMACR in partial atrophy. We evaluated by immunohistochemistry the expression of AMACR and 34ßE12 (cytokeratin high-molecular weight) using the cocktail P504S +34ßE12 in 74 needle prostatic biopsies corresponding to 61 patients. We analyzed a total of 1198 prostate acini (324 acini with adenocarcinoma, 213 normal acini, 190 acini with partial atrophy, 298 acini with post-atrophic hyperplasia, 139 acini with simple atrophy and 34 acini with sclerosing atrophy). In adenocarcinoma acini the staining of AMACR was strong in 251/324 (77.5%) and weak in 73/324 (22.5%). There were no negative acini. In normal acini AMACR was strong in 13/213 (6.1%), weak in 33/213 (15.5%) and negative in 167/213 (78.4%). In partial atrophy, acini showed weak AMACR in 47/190 (24.7%) and were negative in 143/190 (75.3%). There was no strong staining in partial atrophy. The immunoexpression of AMACR was negative in all variants of complete atrophy: simple atrophy, hyperplastic atrophy and sclerosing atrophy. Normal acini showed negative, weak, or strong expression in 167/213 (78.4%), 33/213 (15.5%), and 13/213 (6.1%) acini, respectively. Partial atrophy showed negative, and weak expression in 143/190 (75.3%), and 47/190(24.7%) acini, respectively. No strong positivity was seen in partial atrophy, however, the weak positivity seen in approximately 25% of the acini may be a pitfall for the correct interpretation in the differential diagnosis of cancer and partial atrophy. AMACR was negative in all acini of simple, postatrophic hyperplasia and sclerosing atrophy, therefore, with no help in the differential diagnosis of adenocarcinoma. The distribution of basal cells in simple, postatrophic hyperplasia and sclerotic atrophy was discontinuous and the cells of the secretory compartment showed aberrant expression of 34ßE12 suggesting an intermediate phenotype. Analyzing these results it is concluded that the differential diagnosis of prostate cancer with partial atrophy must be done carefully considering that the expression of AMACR, although weak in our study, can occur in about 25% of the acini. Furthermore, in 23.2% acini of partial atrophy the basal cells are absent. In some cases the microscopic identification of partial atrophy will rely only on morphologic criteria.
Mestrado
Ciencias Biomedicas
Mestre em Ciências Médicas
Moro, Ana Laura Didonet. "Avaliação de caquexia reumatoide em pacientes com artrite reumatoide e sua relação com desfechos clínicos, funcionais e terapêuticos". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/151463.
Texto completoBackground: Rheumatoid arthritis (RA) is a chronic and inflammatory disease that besides articular symptoms leads to loss of muscle mass in presence of stable or increased fat mass (FM), condition defined as rheumatoid cachexia (RC). RC is associated with a worse prognosis, but it is still overlooked in clinical practice. Objective: To evaluate the prevalence of rheumatoid cachexia (RC) in patients with rheumatoid arthritis (RA) and determine its correlation with the features of RA, the level of physical activity and with the current therapy. Methods: Ninety one RA patients in a cross-sectional study underwent total body dual-energy x-ray absorptiometry (DXA) for measurement of total and regional fat mass index (FMI; Kg/m2), lean mass index (LMI; Kg/m2), bone mineral content (BMC; Kg/m2) and fat free mass index (FFMI; Kg/m2) to assess the prevalence of RC. The associations of measures of body composition with RA features - age, diagnosis time, Health Assessment Questionnaire (HAQ), Disease Activity Score in 28 joints (DAS 28), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) -, level of physical activity (measured by International Physical Activity Questionnaire – IPAQ) and current therapy were explored. Results: Mean age was 56,8 ± 7,3 , disease duration 9 years (3 – 18), DAS28 3,65 ± 1,32, HAQ 1,12 (0,25 – 1,87) and use duration of biological agents was 25 months (17,8 – 52,5). Seventeen per cent of the patients had FFMI below the 10th percentile and FMI above the 25th percentile of a reference population and 33% of the patients had FFMI below the 25th percentile and FMI above the 50th percentile, condition known as RC, according to the more recently used definitions. FFMI correlated negatively only with age (r=-0,219; p=0,037) and disease duration (rs=-0,214; p=0,042). FMI correlated positively with CRP (rs=0,229; p=0,029), ESR (rs=0,235; p=0,025), DAS 28 (rs=0,273; p=0,009) and HAQ (rs=0,297; p=0,004). Of the 26 patients using biological therapy, 25 were non cachetic (p=0,033) according to the stricter definition of RC. In another words, 3,8% (n=1) and 23% (n=15) of the patients receiving and not receiving biological agents had RC, respectively (p=0,033). Conclusion: The prevalence of RC was considerable and deserves additional research. Body composition, in this study, particularly FFMI is inversely associated with age and disease duration. Besides that, patients under biological therapy had lower prevalence of RC, suggesting a protective effect of biological agents.
Duriez, Quentin. "Tabagisme et atrophie cérébrale chez le sujet âgé". Thesis, Bordeaux, 2014. http://www.theses.fr/2014BORD0280/document.
Texto completoThe increase in life expectancy seen during the XXth century, followed by an increase in theproportion of elderly, placed the study of brain aging and of its accompanying diseases in thespotlight. This thesis had for goal the study and quantification of the impact of tobaccoconsumption on brain morphological aging in a large cohort of elderly subjects from the Three CitiesStudy. We focused to evaluate and compare its impact, in comparison with other factors known toinfluence brain aging, in longitudinals and cross-sectionals studies. We show that tobacco smokinghas an effect, mainly global, more important than the others cardiovascular risk factors included inthis study and as important as the effect of age. Also, we have found that this effect stops with theconsumption, showing that prevention among the elderly population might be of major interest forsociety. Moreover, analysis have been conducted in men and women separately, allowing us to finddifferential effects of tobacco consumption on the brain morphological aging in the two sexes
BAUMLIN, MARIE-CHRISTINE. "L'atropine, de l'antiquite a nos jours : son interet actuel en anesthesiologie". Strasbourg 1, 1992. http://www.theses.fr/1992STR15045.
Texto completoMarmolejo, Martínez-Artesero Sara. "Novel therapeutic strategy for muscle disorders". Doctoral thesis, Universitat Autònoma de Barcelona, 2021. http://hdl.handle.net/10803/671185.
Texto completoLas alteraciones músculo esqueléticas son ocasionadas por diferentes causas, como son enfermedades crónicas, distrofias musculares, enfermedades neurodegenerativas, lesiones traumáticas causadas a diferentes niveles (nervioso, muscular o óseo) y envejecimiento. Estas alteraciones suelen producir atrofia muscular, que es una reducción en la masa y en la función muscular, y es determinada por un desequilibrio del metabolismo proteico por un exceso en la degradación de las proteínas. El músculo esquelético tiene una capacidad de regeneración limitada de auto-reparación tras un traumatismo o en enfermedades musculares. Esa capacidad de auto-reparación es dada por las células satélites (CSs), que son células madre específicas del músculo que se activan y siguen un proceso de diferenciación dando lugar a nuevas fibras musculares. Actualmente todos los agentes farmacológicos y biológicos disponibles sólo alivian los síntomas clínicos y tienen un efecto limitado o nulo en la progresión de la enfermedad muscular subyacente. En algunos casos, el proceso endógeno de reparación muscular resulta insuficiente, lo que provoca la pérdida de tejido contráctil, la degeneración de las grasas y el tejido cicatricial fibroso, que causan déficits a largo plazo en la estructura y la fuerza muscular. Recientemente hemos descubierto un fármaco neuroprotector, llamado NeuroHeal, para lesiones del nervio periférico (LNP). NeuroHeal está formado por la combinación de dos fármacos ya aprobados (Acamprosato y Ribavirina), facilitando su uso en la clínica, que fue descubierto usando inteligencia artificial y redes basadas en la biología de sistemas. Con el uso de un modelo de LNP severo, observamos que NeuroHeal mejoraba la regeneración de los nervios y reducía la atrofia muscular asociada. Así pues, nos propusimos descifrar el novedoso efecto terapéutico de NeuroHeal para los trastornos del tejido muscular, centrándonos en modelos in vivo de atrofia y lesión muscular. Intentamos dilucidar si NeuroHeal también inducía los mecanismos de protección contra la atrofia y los efectos regenerativos para promover la recuperación del tejido muscular después de un desuso o una lesión. Para saber si NeuroHeal tenía un efecto directo sobre la atrofia muscular, utilizamos dos modelos in vivo de atrofia, uno de denervación muscular y otro de inmovilización de las extremidades posteriores, y un modelo in vitro, la línea celular C2C12 con una inducción de atrofia por TNFα. Observamos que NeuroHeal frenó la reducción de fibras musculares, redujo la actividad catalítica del UPS e indujo una correcta resolución de la autofagia. Para dilucidar si NeuroHeal modulaba la regeneración muscular, utilizamos un modelo in vivo de una lesión muscular quirúrgica que simula las lesiones musculares esqueléticas más frecuentes observadas en la clínica deportiva. NeuroHeal promovió la respuesta regenerativa del músculo esquelético, mejorando la activación y diferenciación de las células satélites, mediante la activación de SIRT1. Esto fue acompañado por un aumento en la contracción muscular y un cambio a fibra de miosina tipo rápida. En ambos casos, observamos que la actividad de SIRT1 era necesaria para los efectos protectores de NeuroHeal. En general, concluimos que NeuroHeal podría utilizarse clínicamente para reducir la atrofia muscular y acelerar la regeneración muscular para diferentes afecciones clínicas como enfermedades neurodegenerativas, lesiones del nervio periférico o lesiones musculares directas, y probablemente también como tratamiento en varias enfermedades musculares debido a su capacidad para activar los mecanismos protectores y miogénicos a través de SIRT1.
Skeletal muscle alterations appear due to different reasons, such as chronic diseases, muscular dystrophies, neurodegenerative diseases, traumatic injuries at different levels (nerve, muscle, or bone), and aging. These alterations usually produce muscle atrophy, which is a reduction of muscle mass and muscle function, and is provoked by protein metabolism imbalance consisting in an excessive protein breakdown. Skeletal muscle has limited regenerative capabilities for self-repair after trauma or muscular diseases. That self-repairing ability is derived by satellite cells (SCs), which are a muscle-specific stem cells that are activated and follow a process of differentiation giving newly formed myofibers. All current available pharmacological and biological agents only relieve clinical symptoms and have limited or no effect on the progression of the underlining muscle disease. In some cases, the endogenous process of muscle repair proves insufficient, leading to loss of contractile tissue, fatty degeneration, and fibrotic scar tissue, which cause long-term deficits in muscle structure and strength. We have recently discovered a neuroprotective drug, termed as NeuroHeal, for peripheral nerve injury (PNI). NeuroHeal is based on the combination of two approved drugs (Acamprosate and Ribavirin), and was discovered using artificial intelligence and systems biology-based networks, which facilitate its readiness for clinical use. Using a model of severe PNI, we observed that NeuroHeal enhanced nerve regeneration and reduced the associated muscle atrophy. Thus, we aimed to decipher the novel therapeutic effect of NeuroHeal for muscle tissue disorders, focusing on in vivo models of muscle atrophy and muscle injury. We pursued to elucidate if NeuroHeal also endorsed protective mechanisms against atrophy and regenerative effects to promote muscle tissue recovery after disuse or injury. In order to know whether NeuroHeal had a direct effect on muscle atrophy, we used two in vivo models of atrophy, muscle denervation and a hindlimb immobilization, and in vitro model, the cell line C2C12 atrophy-induced by TNFα. We observed that NeuroHeal prevented the reduction of myofibers, reduced the catalytic activity of the UPS, and induced a correct resolution of autophagy. To elucidate whether NeuroHeal modulates muscle regeneration, we used an in vivo model of a surgically-induced lesion which mimics the most frequent skeletal muscle lesions observed in human sport clinics. NeuroHeal promoted the regenerative response of the skeletal muscle, enhancing activation and differentiation of the SCs, by the activation of SIRT1. This was accompanied by an increase in muscle contraction and a fast myosin fiber-switch. In both cases, we observed that SIRT1 activity is needed for the protective effects of NeuroHeal. Overall, we conclude that NeuroHeal could be clinically used to reduce muscle atrophy and accelerate muscle regeneration for different clinical affectations such as neurodegenerative diseases, peripheral nerve injuries, or muscle direct injuries, and probably also as a treatment in various muscle diseases due to its ability to activate protective and myogenic mechanisms via SIRT1.
Universitat Autònoma de Barcelona. Programa de Doctorat en Neurociències
Nascimento, Tábata Leal. "Papel da proteína de choque térmico 70 induzível (HSP70) na atrofia muscular e subsequente recuperação". Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/42/42131/tde-17042013-085753/.
Texto completoHeat shock proteins play a key regulatory role in cellular defense. In order to investigate the role of the inducible 70-kDa heat shock protein (HSP70) in skeletal muscle atrophy and subsequent recovery, extensor digitorum longus and soleus muscles from overexpressing HSP70 transgenic mice were immobilized during 7 days and subsequently released from immobilization and evaluated after 7 days. There was a decrease in myofiber cross-sectional area after immobilization in both wild type and HSP70 mice, but only myofibers from HSP70 mice recovered their size. The number of satellite cells and the muscle tetanic contraction were unchanged only in the muscles from HSP70 mice. In addition, the increase of atrogin-1 and MuRF-1 gene expression was attenuated in HSP70 mice. Therefore, our study suggests that the HSP70 is important for structural and functional recovery of muscles after immobilization and this effect might be associated with preservation of satellite cell amount and regulation of atrogenes.