Anemia hemolítica : desafio diagnóstico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Anemia das Células Falciformes: hemólise crónica e vasculopatia cerebral

São apresentados os resultados obtidos no âmbito de dois projetos de investigação no âmbito dos fatores genéticos moduladores da hemólise crónica e da vasculopatia cerebral (AVC e enfartes silenciosos) na Anemia das Células Falciformes. São discutidos os mecanismos subjacentes e hipóteses de uso como alvos terapêuticos.

Hemorheological alterations in sickle cell anemia and their clinical consequences: the role of genetic modulators

Sickle cell anemia (SCA) is an autosomal recessive chronic hemolytic anemia, caused by homozygosity for the HBB:c.20A>T mutation. The disease presents with high clinical heterogeneity, stroke being the most devastating manifestation. This study aimed to identify genetic modulators of severe hemolysis and stroke risk in children with SCA, as well as understand their consequences at the hemorheological level. Sixty-six children with SCA were categorised according to their degree of cerebral vasculopathy (Stroke/Risk/Control). Relevant data were collected from patients’ medical records. Several polymorphic regions in genes related to vascular cell adhesion and tonus were characterized by molecular methodologies. Data analyses were performed using R software. Several in silico tools (e.g. TFBind, MatInspector) were applied to investigate the main variant consequences. Some genetic variants in vascular adhesion molecule-1 gene promoter and endothelial nitric oxide synthase gene were associated with higher levels of hemolysis and stroke events. They modify important transcription factor binding sites or disturb the corresponding protein structure/function. Our findings emphasize the relevance of the genetic variants in modulating the degree of hemolysis and development of cerebral vasculopathy due to their effect on gene expression, modification of protein biological activities related with erythrocyte/endothelial interactions and consequent hemorheological abnormalities in SCA.

Sickle cell anemia : a medical review /

Bibliography: p. 20-26.

Sobre si la clorosis y la anemia son una misma entidad morbosa [Manuscrito] : discurso pronunciado por D. Calisto Landera.

Mode of access: Internet.

Report on recent researches upon the nature and therapy of pernicious anemia,

Bibliography: p. 20-22.

Illinois Equine Infectious Anemia Control Act /

Description based on: 1990.

Anemia de célula falciforme en los recién nacidos y los bebés : guía para los padres.

Mode of access: Internet.

Equine infectious anemia : 2001 update /

Shipping list no.: 2004-0264-P.

Meta-Analysis of the Prognostic Impact of Anemia in Patients Undergoing Percutaneous Coronary Intervention

Peer reviewed

Impact of Hemoglobin Levels and Anemia on Mortality in Acute Stroke : Analysis of UK Regional Registry Data, Systematic Review, and Meta‐Analysis

Funding Sources The NNUH Stroke and TIA Register is maintained by the NNUH NHS Foundation Trust Stroke Services and data management for this study is supported by the NNUH Research and Development Department through Research Capability Funds.

Regulation of lipocalin 2 (Lcn2) gene expression by iron stores, anemia and inflammation

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Study of Rgmc regulation by iron levels, anemia, inflammation and hypoxia

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Rad18 confers hematopoietic progenitor cell DNA damage tolerance independently of the Fanconi Anemia pathway in vivo.

In cultured cancer cells the E3 ubiquitin ligase Rad18 activates Trans-Lesion Synthesis (TLS) and the Fanconi Anemia (FA) pathway. However, physiological roles of Rad18 in DNA damage tolerance and carcinogenesis are unknown and were investigated here. Primary hematopoietic stem and progenitor cells (HSPC) co-expressed RAD18 and FANCD2 proteins, potentially consistent with a role for Rad18 in FA pathway function during hematopoiesis. However, hematopoietic defects typically associated with fanc-deficiency (decreased HSPC numbers, reduced engraftment potential of HSPC, and Mitomycin C (MMC) -sensitive hematopoiesis), were absent in Rad18(-/-) mice. Moreover, primary Rad18(-/-) mouse embryonic fibroblasts (MEF) retained robust Fancd2 mono-ubiquitination following MMC treatment. Therefore, Rad18 is dispensable for FA pathway activation in untransformed cells and the Rad18 and FA pathways are separable in hematopoietic cells. In contrast with responses to crosslinking agents, Rad18(-/-) HSPC were sensitive to in vivo treatment with the myelosuppressive agent 7,12 Dimethylbenz[a]anthracene (DMBA). Rad18-deficient fibroblasts aberrantly accumulated DNA damage markers after DMBA treatment. Moreover, in vivo DMBA treatment led to increased incidence of B cell malignancy in Rad18(-/-) mice. These results identify novel hematopoietic functions for Rad18 and provide the first demonstration that Rad18 confers DNA damage tolerance and tumor-suppression in a physiological setting.