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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Uso de IL-2 humana recombinante em pacientes com imunodeficiência comum variável / Use of recombinant human IL-2 in patients with common variable immunodeficiency

Narciso, João Henrique Fagundes Bastos 06 May 2008 (has links)
Na imunodeficiência comum variável (ICV) têm sido descritas alterações de linfócitos T, incluindo a produção diminuída da interleucina-2 (IL-2). Desde que a IL-2 pode promover a produção de imunoglobulinas in vitro, nosso principal objetivo foi investigar os efeitos in vivo do tratamento com IL-2 recombinante (IL-2r) em pacientes com ICV. Foram selecionados 4 pacientes que apesar de tratamento adequado com imunoglobulina EV apresentavam infecções recorrentes. Após um período de observação de 12 meses, os pacientes receberam doses crescentes de IL-2r durante 16 semanas com reposição de imunoglobulina apenas se a IgG sérica atingisse níveis menores do que 400mg/dL. A seguir, permaneceram em observação por mais 12 meses recebendo imunoglobulina . A gravidade das infecções foi avaliada segundo um \"score\" numa escala de 3 a 10. A avaliação in vitro incluiu: quantificação dos níveis de IgG, IgA e IgM séricas; resposta linfoproliferativa à PHA; populações linfocitárias CD4+, CD8+, CD19+ e CD25+ no sangue periférico. As reações adversas à IL-2r foram leves e localizadas. Houve redução aparente do número e gravidade das infecções durante os 12 meses subseqüentes ao término da IL-2r. Os níveis da IgG sérica e das células CD4+, CD8+ e CD19+ mantiveram-se estáveis durante todo o estudo. Em 3 pacientes houve relação entre melhora clínica e aumento da proporção de linfócitos T CD25+. Isto permite supor que a remissão de infecções em alguns pacientes com ICV , sob terapêutica com IL-2r associada ou não à imunoglobulina EV, esteja parcialmente relacionada à melhora da imunidade celular. Adicionalmente, nossos dados indicam que a IL-2r pode ser utilizada de modo seguro nas dosagens e período utilizados como terapêutica adjuvante em alguns pacientes com ICV que apresentam infecções recorrentes e má resposta terapêutica à imunoglobulina endovenosa / In Common Variable Immunodeficiency (CVID) T cell function may be impaired and interleukin-2 (IL-2) production diminished. Since IL-2 stimulates immunoglobulin production in vitro, the aim of this study was to determine the in vivo effects of recombinant interleukin-2 (rIL-2) in patients with CVID. We selected four CVID patients, who despite intravenous immunoglobulin infusion (IVIG) had recurrent infections. After a twelve-month run-in period, escalating dosages of rIL-2 were administered during 16 weeks, during which rescue IVIG treatment was performed whenever serum IgG levels dropped below 400 mg/dL. During follow-up (12 months), patients were observed and treated with IVIG. Infection severity was assessed using a 3 to 10 infection score. In vitro analysis included: measurement of serum levels of IgG, IgA and IgM; lymphocyte proliferative responses to phytohaemaglutinin (PHA); CD4+, CD8+,CD19+ and CD25+ lymphocyte populations in peripheral blood. Few local side-effects were observed in 2 patients. In the follow-up period after rIL-2 treatment, patients experienced reduction of the number and severity of infections. Levels of serum IgG, CD4+, CD8+ and CD19+ were stable throughout the study. In 3 patients we observed a relation between improvement of clinical parameters and number of T CD25+ cells. These findings suggest that remission of infections in some CVID patients treated with rIL-2, in combination or not with IVIG is, in part, associated with the improvement of cell immunity. Additionally, our results indicate that rIL-2 administration is safe and may serve as adjuvant therapy in some CVID patients with recurrent infections and poor response to IVIG treatment
2

Uso de IL-2 humana recombinante em pacientes com imunodeficiência comum variável / Use of recombinant human IL-2 in patients with common variable immunodeficiency

João Henrique Fagundes Bastos Narciso 06 May 2008 (has links)
Na imunodeficiência comum variável (ICV) têm sido descritas alterações de linfócitos T, incluindo a produção diminuída da interleucina-2 (IL-2). Desde que a IL-2 pode promover a produção de imunoglobulinas in vitro, nosso principal objetivo foi investigar os efeitos in vivo do tratamento com IL-2 recombinante (IL-2r) em pacientes com ICV. Foram selecionados 4 pacientes que apesar de tratamento adequado com imunoglobulina EV apresentavam infecções recorrentes. Após um período de observação de 12 meses, os pacientes receberam doses crescentes de IL-2r durante 16 semanas com reposição de imunoglobulina apenas se a IgG sérica atingisse níveis menores do que 400mg/dL. A seguir, permaneceram em observação por mais 12 meses recebendo imunoglobulina . A gravidade das infecções foi avaliada segundo um \"score\" numa escala de 3 a 10. A avaliação in vitro incluiu: quantificação dos níveis de IgG, IgA e IgM séricas; resposta linfoproliferativa à PHA; populações linfocitárias CD4+, CD8+, CD19+ e CD25+ no sangue periférico. As reações adversas à IL-2r foram leves e localizadas. Houve redução aparente do número e gravidade das infecções durante os 12 meses subseqüentes ao término da IL-2r. Os níveis da IgG sérica e das células CD4+, CD8+ e CD19+ mantiveram-se estáveis durante todo o estudo. Em 3 pacientes houve relação entre melhora clínica e aumento da proporção de linfócitos T CD25+. Isto permite supor que a remissão de infecções em alguns pacientes com ICV , sob terapêutica com IL-2r associada ou não à imunoglobulina EV, esteja parcialmente relacionada à melhora da imunidade celular. Adicionalmente, nossos dados indicam que a IL-2r pode ser utilizada de modo seguro nas dosagens e período utilizados como terapêutica adjuvante em alguns pacientes com ICV que apresentam infecções recorrentes e má resposta terapêutica à imunoglobulina endovenosa / In Common Variable Immunodeficiency (CVID) T cell function may be impaired and interleukin-2 (IL-2) production diminished. Since IL-2 stimulates immunoglobulin production in vitro, the aim of this study was to determine the in vivo effects of recombinant interleukin-2 (rIL-2) in patients with CVID. We selected four CVID patients, who despite intravenous immunoglobulin infusion (IVIG) had recurrent infections. After a twelve-month run-in period, escalating dosages of rIL-2 were administered during 16 weeks, during which rescue IVIG treatment was performed whenever serum IgG levels dropped below 400 mg/dL. During follow-up (12 months), patients were observed and treated with IVIG. Infection severity was assessed using a 3 to 10 infection score. In vitro analysis included: measurement of serum levels of IgG, IgA and IgM; lymphocyte proliferative responses to phytohaemaglutinin (PHA); CD4+, CD8+,CD19+ and CD25+ lymphocyte populations in peripheral blood. Few local side-effects were observed in 2 patients. In the follow-up period after rIL-2 treatment, patients experienced reduction of the number and severity of infections. Levels of serum IgG, CD4+, CD8+ and CD19+ were stable throughout the study. In 3 patients we observed a relation between improvement of clinical parameters and number of T CD25+ cells. These findings suggest that remission of infections in some CVID patients treated with rIL-2, in combination or not with IVIG is, in part, associated with the improvement of cell immunity. Additionally, our results indicate that rIL-2 administration is safe and may serve as adjuvant therapy in some CVID patients with recurrent infections and poor response to IVIG treatment
3

Tau protein, biomarker Alzheimerovy choroby: in vitro fosforylace a charakterizace tau reaktivních protilátek / Tau protein, a biomarker of Alzheimer's disease: in vitro phosphorylation and tau-reactive antibodies characterization

Hromádková, Lenka January 2018 (has links)
Tau protein, a microtubule-associated protein localized in axonal projections of neurons, is a key molecule in the pathology of Alzheimer's disease (AD), the most common cause of dementia in the elderly population. Tau belongs to the group of natively unfolded proteins without globular structure and is prone to numerous posttranslational modifications (PTMs). Under pathological conditions, abnormal PTMs and misfolding of tau protein occurs and leads to oligomerization and aggregation into paired helical filaments forming neurofibrillary tangles, the histopathological hallmark of AD. Currently available drugs applied in AD treatment can only slow the disease progression and those, which halt the AD-specific neurodegenerative processes, are still missing. Very promising and evolving therapeutic approach is immunotherapy, and even immunomodulation by administration of intravenous immunoglobulin (IVIG) products, a reservoir of natural antibodies from the plasma of healthy donors, has been already tested. The discovery of naturally occurring antibodies directed to tau (nTau-Abs) in body fluids of both AD and healthy subjects and their presence in IVIG begin the investigation of their therapeutic potential. Considering a wide range of possible modifications of tau and of various tau species (oligomers,...

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