Teses em Neurociências e Biologia Celular (Doutorado) - PPGNBC/ICB
URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/2390
O Doutorado Acadêmico pertence ao Programa de Pós-Graduação em Neurociências e Biologia Celular (PPGNBC) do Instituto de Ciências Biológicas (ICB) da Universidade Federal do Pará (UFPA).
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Item Acesso aberto (Open Access) Avaliação in vivo do potencial efeito protetor da prolactina contra danos causados pelo metilmercúrio(Universidade Federal do Pará, 2022-04) CUNHA, Lorena Araújo da; ROCHA, Carlos Alberto Machado da; http://lattes.cnpq.br/5789536737681588; BURBANO, Rommel Mario Rodriguéz; http://lattes.cnpq.br/4362051219348099; https://orcid.org/0000-0002-4872-234XBiodegradable metals, such as mercury, accumulate in living organisms throughout their lives (bioaccumulation) and also in food webs (biomagnification), and can reach high concentrations in humans. Human contamination by mercury found in drinking water and food can be common, especially in riverine communities that depend on fish as their main source of protein. In vitro studies with human cell lines exposed to methylmercury showed that prolactin has cytoprotective properties against cytotoxic and mutagenic effects of this metal, and can act as a co-mitogenic factor and apoptosis inhibitor. The present study investigated, in vivo, the protective potential of prolactin against the toxic effects of methylmercury in mammals, using the mouse (Mus musculus) as a model. Biomarkers of genotoxicity (comet assay and micronucleus test) and oxidative stress (lipid peroxidation and activity of CAT and SOD enzymes), together with histological (in liver, kidney and brain tissue samples) and biochemical (renal and hepatic and measurement of Hg and PRL in the blood), were used to verify the protective potential of prolactin in mice exposed to methylmercury. It was observed, in a more expressive way, a reduction in the alterations of the renal and hepatic biochemical parameters and of the mutagenic effects in the presence of prolactin, in comparison with the isolated effects of the metal. When prolactin was used together with the metal, a decrease in histological damage and an increase in SOD enzyme activity were also observed. The study results indicate that prolactin has protective effects against toxic impacts of methylmercury.Item Acesso aberto (Open Access) A infecção por Plasmodium berghei (ANKA) induz um quadro de encefalopatia hepática em modelo murino de malária não complicada(Universidade Federal do Pará, 2024-02) KAUFFMANN, Nayara; SILVA, Anderson Manoel Herculano Oliveira da; http://lattes.cnpq.br/8407177208423247; https://orcid.org/0000-0003-4022-8096; OLIVEIRA, Karen Renata Herculano Matos; http://lattes.cnpq.br/3032008039259369Introduction. The main changes in hepatocellular dysfunction associated with malaria are liver failure, hepatosplenomegaly and increased liver enzymes. Several studies have already elucidated that such liver changes can be caused by increased ammonia levels, which can consequently lead to dysfunction in the central nervous system (CNS), causing hepatic encephalopathy, culminating in an increase in the inflammatory response, cerebral edema, deregulation of neurotransmitters and cognitive and locomotor changes. Objective: To characterize possible changes in the central nervous system resulting from liver injury induced by Plasmodium berghei ANKA infection in a murine model of uncomplicated malaria. Methodology. For this, mice of the Balb-c lineage (20- 25g) were used between 45-54 postnatal days (CEUA nº 2229290317), inoculated with ~106 parasitized erythrocytes intraperitoneally. The experimental design was divided into two parts: Firstly, the survival curve, parasitemia, body mass, clinical signs, hepatic and histological changes, neurochemistry, presence of cerebral edema, vascular extravasation, inflammatory response, behavioral changes and quantification of blood levels were characterized. ammonia in the control and PbA groups. Subsequently, a treatment with lactulose was carried out to verify whether the changes found in the previous experiments were due to the increase in ammonia levels in the animals' brains. For this purpose, the groups were divided into: control group, lactulose 3mg/kg, PbA and PbA+lactulose 3mg/kg, in which the survival curve, parasitemia and locomotor activity were evaluated using the SHIRPA protocol. The results were expressed as mean+standard deviation. ANOVA (one way) was performed, post Tukey test, considering p<0.05 as significant. Results. Our data demonstrated that the PbA group presented changes in liver functions such as increased levels of AST and ALP, BT and BD, morphological changes such as hepatosplenomegaly, in addition to histological changes showing inflammatory infiltrate, deposition of malarial pigment and Kupffer cell hyperplasia, thus demonstrating a picture of liver failure. After characterizing the liver injury, we sought to understand whether these changes could generate impairment in the CNS, which we observed cognitive and motor impairment, in addition to changes in the levels of the neurotransmitters GABA and glutamate, accompanied by an increase in the inflammatory response, cerebral edema and dysfunction in the liver. blood-brain barrier. Once liver failure was demonstrated and, consequently, the presence of cognitive and behavioral changes, we sought to evaluate ammonia levels in the brains of control and PbA animals in the initial phase of infection. In this sense, the quantification of ammonia levels showed an increase on the 10th d.p.i., in brain tissue when compared to the control group, in which the levels were within expectations in relation to locomotor activity, when applying the protocol in the infected and treated group with lactulose, it was possible to observe that the PbA group showed changes in motor behavior, when compared to the control group. In contrast, the PbA+Lactulose 3mg/kg group showed an attenuation of cognitive and behavioral changes, showing that therapy with lactulose can attenuate the cognitive condition regarding motor behavior, muscle strength and tone, reflexes, and sensory function. Conclusion. We conclude that liver failure causes hepatic encephalopathy in a murine model of uncomplicated malaria, which culminates in changes in the central nervous system, by increasing ammonia levels in the brain, and by sequestering ammonia with the help of treatment. with lactulose at a dose of 3mg/kg, it can attenuate the neurological damage of animals with uncomplicated malaria, demonstrating that the behavioral changes come from a condition of hepatic encephalopathy, caused by increased levels of ammonia in the cortex of infected animals.Item Acesso aberto (Open Access) O papel da biologia molecular no diagnóstico, epidemiologia molecular e perfil de sensibilidade de cepas de M. leprae em região endêmica da Amazônia Brasileira(Universidade Federal do Pará, 2023-10) BOUTH, Raquel Carvalho; SILVA, Moises Batista da; http://lattes.cnpq.br/5525661855611118; SALGADO, Claudio Guedes; http://lattes.cnpq.br/2310734509396125Leprosy is a chronic disease, disabling and difficult to diagnose in all its clinical manifestations. The aims of this study were to identify the laboratory marker that presents greater sensitivity and specificity for diagnosis, to genetically understand the strains of M. leprae circulating in the Pará State and to evaluate the region drug resistance reality. A multidisciplinary team evaluated 833 individuals using different strategies at URE Dr. Marcello Candia, and in 14 municipalities in Pará. All individuals were clinically evaluated, and biological samples were collected for comparative analysis of the results of slit skin smear microscopy, molecular detection of the bacillus by qPCR RLEP in ear lobes, IgM Anti-PGL-I antibodies titration, and histopathological lesion skin biopsy, lesion qPCR RLEP, and M. leprae whole genome sequence. 351 cases were clinically diagnosed, divided into groups: individuals with classic and non-classic clinical manifestations, asymptomatic cases and 482 healthy contacts. The comparative analysis of the results demonstrated that ear lobe RLEP detection presented greater sensitivity, specificity and agreement with the clinical diagnosis (72.5, 70.4 and Kappa = 0.42 respectively), followed by skin biopsy (sensitivity= 65.8%), Anti-PGL-I serology with 61.2% (52.2 specificity), slit smears skin (41.7%) and histopathology (25.0%). The RLEP association to serology, showed an increased in laboratorial correlation with the clinic diagnosis (Kappa= 0.55). The circulant streains evaluation, we detected that the most frequent profile was profile 4N (52/66- 78.8%), followed by 4P subtype (4/66- 6.1%), 3I (9/66 -13, 6%), and 1D (1/66- 1.5%). In the drug resistance analysis, we obtained 3/101 (3%) mutation in folP1 gene, conferring dapsone resistance. 1/40 (2.5%) gyrB mutations, conferring quinolones resistance. The gyrB resistant strain also had mutation in folP1, and in the fadD9, ribD, pks4 and nth genes, considered a hypermutant strain. Our findings showed that qPCR RLEP molecular test associated with Anti-PGL-I serology were a good tool for leprosy laboratorial diagnosis, and that type 4 strains, originating in Africa, are the most frequent type in the Amazon. And we find drug-resistant strains, and a hypermuted strain circling in the region. The strains were resistant to the current polychemotherapy regimen and the alternative drug regimen.