DSpace Coleção: Antigo Programa de Pós-Graduação em Ciências Fisiológicas

Desenvolvimento de um imunossensor eletroquímico pioneiro para detecção precisa da leishmaniose visceral humana com antigeno recombinante purificado de leishmania

Tue, 29 Oct 2024 00:00:00 GMT

Título: Desenvolvimento de um imunossensor eletroquímico pioneiro para detecção precisa da leishmaniose visceral humana com antigeno recombinante purificado de leishmania Abstract: Leishmaniasis is a disease that affects a large part of the population of Latin America, especially in Brazil. It has a high mortality rate if left untreated. The main diagnostic methods currently used are based on signs and symptoms suggestive associated with parasitological and/or immunological tests, however, such tests have disadvantages such as low sensitivity and specificity, high cost, need for equipped laboratories and qualified professionals. Thus, it is necessary to have a fast, accurate, low-cost, portable diagnosis that has good sensitivity and specificity. In this study, a recombinant antigen called DTL-4 was used because of its potential to improve the sensitivity and specificity of the tests because it only allows specific binding with the antibody in the serum of patients with the disease. The results of the proposed immunosensor showed an estimated detection limit of 0.0442 ng mL−1. The absence of modifications with gold nanoparticles is another interesting point when we compare the cost related to the biosensor in question with other diagnostic methods. Thus, the proposed immunosensor has low cost, high specificity and sensitivity. In this way, the biosensor in question shows promise for validating the diagnostic platform and its future portable use in public health. Tipo: Dissertação

Desenvolvimento de imunossensor para detecção específica de Leishmanioses em eletrodo de grafite com ouro eletrodepositado

Sat, 25 May 2019 00:00:00 GMT

Título: Desenvolvimento de imunossensor para detecção específica de Leishmanioses em eletrodo de grafite com ouro eletrodepositado Abstract: This work describes the methodology for electrochemical diagnosis of Leishmaniasis (LSH), it suppresses cross-reaction of Chagas disease (DC). Cross-reactions happen in commercially available (ELISA) tests and thus do not allow correct beginning and / or early treatment. Knowing the sensitivity of the sensor, total antigens tested in the ELISA were methodologically appropriate to the sensor. There were used 3 kinds of screen-printed electrodes: gold, graphite and graphite with electrodeposited gold film to observe biomolecular interaction in the work’s electrode and recognizing the samples. Antibodies present in serum from patients with diverse types of Chagas' Disease and Leishmaniases were chosen. The electrochemical analyses took place from the redox analysis of Ferri solution/Potassium ferrocyanide. The results showed that the graphite electrode with gold electrodeposited film guaranteed effective adsorption of the total antigens so that the epitope of specific recognition for Leishmaniasis occurred efficiently and without cross-reaction with the evaluated Chagas disease. The oxidation current peaks reduced linearly after the recognition, and still being able to notice the discrimination between kinds of diseases. Pool of sera or specific kinds (digestive, cardiac, undetermined Chagas / Acute and chronic Leishmaniasis) presented remarkable discrimination in the immunosensor. Comparative analyses with indirect ELISA were performed with the same groups, presenting cross reactions. Furthermore, the sensor presented relative stability within 5 days. Thus, we presented an innovative proposal of an immunosensor that suppressed the cross reaction to Chagas disease for specific detection of Leishmaniasis. Tipo: Dissertação

Modos de ligação e interação entre mediadores lipídicos das séries Ômega-3 e Ômega-6 e o receptor ativado por proliferadores de peroxissomo gama (PPARy)

Thu, 07 Nov 2024 00:00:00 GMT

Título: Modos de ligação e interação entre mediadores lipídicos das séries Ômega-3 e Ômega-6 e o receptor ativado por proliferadores de peroxissomo gama (PPARy) Abstract: Peroxisome Proliferator-Activated Receptors (PPARs) are transcription factors that belong to the Nuclear Receptor (NR) superfamily and play fundamental roles in the regulation of genes involved in lipid and carbohydrate metabolism, regulation of the inflammatory response, and control of cell differentiation. Three isotypes are expressed in the human body: PPARα, PPARβ/δ and PPARγ, each with distinct tissue distribution and functions. Structurally, PPARs have domains in common with most NRs, and their transcriptional activity depends on heterodimerization with another NR, the Retinoid X Receptor RXR, and on activation by agonist molecules, which trigger conformational changes essential for the recruitment of coactivator proteins and the initiation of transcription of target genes. The great interest in the effects of PPARγ in improving insulin sensitivity has led to the discovery of its role as immunomodulator agent and of its genuine natural ligands, fatty acids and their oxidized metabolites, such as oxylipins, generated by stimuli from the inflammatory microenvironment. These ligands include the n-3 and n-6 series essential fatty acids (EFAs) and their derivatives, which act as lipid mediators (LMs), significantly influencing the resolution of inflammatory processes. Although full PPARγ agonists, such as thiazolidinediones (TZDs), are effective in improving insulin sensitivity, their considerable adverse effects boosted the search for partial agonists, usually natural ligands, such as LMs, as alternatives for PPARγ activation with reduced adverse effects. Through a systematic search on PDB, 20 PPARγ complexes were identified with 17 different n-3 and n-6 LMs bound to the receptor’s ligand binding site. Based on these crystals and on experimental and computational studies, this review details the binding modes and interactions between PPARγ ligand binding site’s amino acid residues and its potential agonist MLs, also highlighting the conformational changes of crucial regions for receptor activation, such as the Ω-loop, beta sheets and -helices H3 and H12, resulting from the interactions with different ligands. The findings made evident the complexity and diversity of the interactions of MLs n-3 and n-6 with PPARγ, highlighting key residues for the rational design of new drugs that mimic endogenous ligands and selectively modulate receptor activity. In addition to reaffirming the importance of a diet, that provides optimal amounts of EFAs for immune and metabolic homeostasis, a deeper understanding of the mechanisms of binding and activation of PPARγ by its natural endogenous ligands has proven crucial for the development of new agonists that achieve effective and safer therapeutic results. Tipo: Tese

Alterações histopatológicas na mucosa gástrica e nível sérico de gastrina em pacientes chagásicos com e sem infecção pelo Helicobacter pylori

Thu, 18 Jun 2015 00:00:00 GMT

Título: Alterações histopatológicas na mucosa gástrica e nível sérico de gastrina em pacientes chagásicos com e sem infecção pelo Helicobacter pylori Abstract: .Chagasic patients with digestive form have abnormally high gastrin release and low gastric acid secretion. Likewise, H. pylori infection can also induce hypergastrinemia. Thus, we aimed to evaluate whether hypergastrinemia occurs in patients with the other clinical forms of Chagas disease, co-infected or not by H. pylori. Moreover, serum gastrin levels were associated with CagA-positive H. pylori strains and with gastric histological and endoscopic features. The patients evaluated were divided into two groups, one group comprising chagasic (with digestive form) and non-chagasic patients undergoing upper endoscopy and the other group comprising chagasic (with different clinical forms) and non-chagasic patients who did not underwent this procedure. H. pylori (HP) infection was assessed by histology, detection of 16S rRNA gene in gastric tissue by PCR, serology and the 13C-urea breath test. Gastrin concentration was measured by chemiluminescence assay. CagA expression was examined by PCR. Histological scores were evaluated according to Update Sydney System. The mean serum basal gastrin was significantly higher among chagasic than non-chagasic patients who underwent upper endoscopy than those who did not (p<0.05). No significant differences in the basal serum gastrin concentrations were observed among the different clinical forms of Chagas disease neither among HP-positive and HP-negative patients, chagasic or controls. Patients with digestive form or with the other clinical forms of Chagas disease have increased basal serum gastrin level. Moreover, our findings do not support a direct role of H. pylori infection in the increasing gastrin secretion among chagasic patients. Tipo: Dissertação