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Células dendríticas foliculares: avaliação imunofenotípica no linfoma de Hodgkin clássico subtipo esclerose nodular

2026-03-20T13:24:33Z

Título: Células dendríticas foliculares: avaliação imunofenotípica no linfoma de Hodgkin clássico subtipo esclerose nodular Autor(es): Almeida, Juliêta Maria Mendes Frota de Abstract: The follicular dendritic cells are the most important antigen presenting cells and have an important role in B cell immune response. Classic Nodular Sclerosis Hodgkin's Lymphoma (CNSHL) is a lymphoid neoplasm, more specifically from germinal center (GC) B cells, presenting with aggregates of follicular dendritic cells (FDC), Hodgkin/Reed Sternberg cells and variants and B cells forming complexes related to the GC, suggesting an association between nodular sclerosis and germinal center formation. CNSHL represents 70% of classic Hodgkin's lymphomas and has a favorable prognosis. Histologically it is characterized by a nodular pattern, collagen bands and lacunar cells. The goal of this study was the evaluation of the follicular dendritic cell by immunophenotyping with pS100 and fascin, in lymph node or mediastinal mass biopsies from patients with previously diagnosed classic nodular sclerosis Hodgkin's Lymphoma, trying to identify criteria as prognostic factors. 159 charts were reviewed and 38 patients were selected for the study. From the selected group 55.2% were males with a male to female ratio of 1.23:1 and a median age of 29.3 years. 52.6% were in clinical stage 1-11 and 68.4% had systemic symptoms (B). Multiple or isolated peripheral adenomegaly was present in all cases. The first lymph node site was cervical in 58% of the cases. 38 biopsy specimens were analysed and 57.9% were of nodular sclerosis subtype II. Immunohistochemistry showed 100% positivity for CD30 and 68.4% for CD15. The follicular dendritic cells were identified by pS100 and fascin antibodies through the Peroxidase-antiperoxidase Streptavidin avidin-biotin indirect immunoenzimatic technique, which was performed in pre-treated slides with the biopsy specimens included in paraffin blocks. The marking with pS100 didn't show good visualization of the network of follicular dendritic cells, and was useful as a generic marker. Fascin was the gold-standard for follicular dendritic cells, showing its positivity by the brown color. The CDF1 pattern was present in 7.9%, CDF2 in 47.4% and CDF3 in 44.7%. There was no relation between the presence of the follicular dendritic cell and sex, age, clinical stage, laboratorial parameters, or response to treatment, but a tendency for the association (p=0.056) between the subtypes of classical nodular sclerosis Hodgkin's lymphoma was demonstrated. The patients with follicular dendritic cells present in their biopsies have been watched for a longer period of time of about 32.9 months. This enabled a significant statistical association (p=0.001) between the presence of follicular dendritic cells and length of follow-up Tipo: Dissertação

Avaliação da contratilidade e do estresse oxidativo em íleo e cólon e análise proteômica do plasma de camundongos C57BL6J expostos ao metilmercúrio

2026-01-21T16:07:23Z

Título: Avaliação da contratilidade e do estresse oxidativo em íleo e cólon e análise proteômica do plasma de camundongos C57BL6J expostos ao metilmercúrio Autor(es): Buzaglo, Alexander Vasconcelos Abstract: Methylmercury (MeHg) is an organic mercury (Hg) compound with high toxicity due to its easy absorption after exposure. MeHg rapidly distributes throughout all tissues, crossing the blood-brain barrier and the epithelial barrier in the central nervous system and gastrointestinal tract, respectively, and can lead to a wide range of debilitating symptoms and death. The aim of this study was to elucidate the effects of oral methylmercury chloride exposure on body weight gain, intestinal motility, oxidative stress, and the proteomic profile in the plasma of intoxicated animals compared with the control group. For this purpose, 46 adult male C57BL6 mice from the animal facility of the Drug Development Center (NPDM) under pathogen-free conditions were used. Mice aged 60 to 90 days with body weights between 15 and 20 g, were divided into two groups: the control group receiving a saline solution by gavage and the intoxicated group receiving a methylmercury chloride solution (2 mg/kg diluted in saline) by gavage for 14 consecutive days. All animals were weighed every 3 days. Seven days after the end of intoxication, the animals were euthanized, and samples of hair, blood, duodenum, ileum, and colon were collected. Quantification of Hg in the hair, evaluation of ileum and colon contractility ex vivo, in a bath chamber for isolated tissues after exposure to potassium chloride (20-160 mM) and carbachol (0.1-100μM), evaluation of oxidative stress in the ileum and colon (tissue concentrations of glutathione-GSH, malondialdehyde-MDA and catalase-CAT) and proteomic analysis of plasma were performed. A significant reduction in the curve of percentage weight gain (% of initial weight) (p<0.05) when compared to the control group. Furthermore, elevated Hg levels in the hair were observed in the intoxicated group compared to the control group (Difference between means ± SEM: 6067 ± 2180). There was no significant difference in intestinal contractility in the ileum or colon between the groups. A significant increase in GSH was detected in the colon and a significant increase of CAT in the ileum of intoxicated animals (p=0.05). Significant alterations were observed in the proteomics analyses between groups, notably an increase in the expression of apolipoproteins E and H and a reduction in phosphatidylcholinesterol acetyltransferase, suggesting metabolic alterations; an increase in the expression of complement factor I, the Mu constant of the heavy chain and the C region of the Ig alpha chain, and a reduction in the C9 and C4b components of the complement system, suggesting a systemic response. We also observed an increase in the expression of the fibrinogen alpha chain and coagulation factor X and a reduction in the expression of the fibrinogen beta chain, suggesting altered liver function and prothrombotic conditions; a reduction in selenoprotein P, expected in models of mercury intoxication without selenium supplementation, indicating deficiencies in this element caused by mercury intoxication; and a reduction in peroxiredoxin 2 levels, that may affect the net antioxidant capacity. In summary, these results corroborate the known deleterious effects of mercury toxicity on the intestinal tract and contribute to the identification of potential proteomic biomarkers. Further studies are needed to confirm these findings, especially in clinical trials. Tipo: Dissertação

Síndromes mielodisplásticas [manuscrito] : caracterizacão morfológica e imunohistoquímica quanto a expressão da proteína p 53

2025-12-12T16:21:30Z

Título: Síndromes mielodisplásticas [manuscrito] : caracterizacão morfológica e imunohistoquímica quanto a expressão da proteína p 53 Autor(es): Magalhães, Silvia Maria Meira Abstract: Summary The p53 gene is currenuy thought to be a tumor suppressor gene, and its alterauons have been suggested to be involved m the pathogenesis of several human malignajicies. The piirpose of fhe present study was fhe evaluation of histológica! findings and the uiununohistochemical study ofp53 egression on bone marrow biopsy from uiirty- three patients in which a myelodysplasuc syndrome (MDS) was diagnosed. Forty- three bone marrow biopsies were reü-ospecüvely reviewed, and relationship among the different histological parajmeters as weU as clinicopafhological correlations were looked for. Histological analysis showed in 78,8% of cases a hypercellular, in 12,1% a hypocellular and in 9,1% a norniocellular bone marrow. Dysraegakaryopoiesis was the inost prominent abnormality of the hematopoietic series, detected in 72,7% of cases. Abnormal localization of immature precursors occurred in 39,4% of patients and increase in reticulin fibers occurred in 34,4%. The frequency oflymphoid nodules in our cases (27.3%) was higher fhan that reported by others with no relauonship with age, but significanuy related to Üückenmg of Uie reticulin network . Nuclear accumulaüon ofp53 protein was foimd m 15,2% offhe cases whereas control subjects were imiformly negaüve for p53 protein. All the five MDS cases that exhibited positive p53 reaction had some kind of disease progression, namely a more advanced FAB subtype and/or acute leukenua. A p53 immunoreactivity was therefore significanuy related to biological aggressiveness and progression of the disease. The results suggest that p53 mutauons may contribute, albeit rarely, to the development of MDS and, once present, may confer a growth advantage to myeloid cells and therefore is useful for predicting the evoluüon. MDS is heterogeneous not only in its phenotype but also in the Kciolecular niechanism of its genesis and progression. More extended and detailed study is necessary to understand the molecular basis of MDS development. The major aim is a more specific and effective treatment of these pauents. Tipo: Dissertação

Aplicações clínicas de sequenciamento de nova geração: da genômica em neuropsiquiatria ao desenvolvimento de um protocolo de metagenômica clínica no Ceará

2025-10-20T22:50:43Z

Título: Aplicações clínicas de sequenciamento de nova geração: da genômica em neuropsiquiatria ao desenvolvimento de um protocolo de metagenômica clínica no Ceará Autor(es): Silva, Carlos Antônio de Arroxelas Abstract: The etiological elucidation of complex neuropsychiatric and infectious disorders represents a critical challenge within Brazil’s Unified Health System, often resulting in prolonged diagnostic journeys. This study aimed to evaluate the clinical applications of next-generation sequencing through genomic and metagenomic approaches conducted at Fiocruz Ceará in complex clinical cases referred from tertiary care in Fortaleza. The genomic approach (whole-exome sequencing) was applied to a cohort of 17 patients, subdivided into a psychiatric cohort (n=9) and a neurological cohort (n=8), while metagenomics was employed to investigate a case of neuroinfection without confirmatory diagnosis using conventional methods. Concurrently, an operational research component, including a participatory assessment with the technical team, mapped systemic barriers in the diagnostic pathway. Genomic investigation revealed clinically relevant findings across the cohort and enabled the establishment of a highly probable molecular diagnosis in 37.5% of the neurological subcohort with specialized clinical curation, notably highlighting the identification of a rare NIT1 variant in a 50-year-old patient with a history of leukodystrophy. Metagenomic analysis was decisive for the confirmatory diagnosis of progressive multifocal leukoencephalopathy caused by John Cunningham virus in an HIV-positive patient. Operational research quantified barriers, identifying the lack of clinical information as the main communication gap (reported by 100% of the team). These results, integrating clinical and operational evidence, supported the development of a collaborative technical-operational protocol, structured under the Clinical–Wet–Dry model, to integrate next-generation sequencing into Ceará’s health network in articulation with Fiocruz Ceará. In conclusion, the application of next-generation sequencing, when guided by a translational approach, not only substantially increases diagnostic yield but also generates a feasible, evidence-based implementation model for incorporating precision technologies into the healthcare system, with the potential to optimize clinical management and strengthen health surveillance. Tipo: Dissertação