Programa de Pós-Graduação em Neurociências e Biologia Celular - PPGNBC/ICB

URI Permanente desta comunidadehttps://repositorio.ufpa.br/handle/2011/2374

O Programa de Pós-Graduação em Neurociências e Biologia Celular (PPGNBC) é parte integrante do Instituto de Ciências Biológicas (ICB) da Universidade Federal do Pará (UFPA), sendo constituído por: Mestrado e Doutorado em Neurociências e Biologia Celular, com área de concentração em Neurociências ou Biologia Celular.

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Análise da ação cicatrizante dos extratos da folha, pecíolo e caule da Montrichardia linifera (Arruda) Schott in vitro
(Universidade Federal do Pará, 2020-02-17) BASTOS, Aline Costa; YAMADA, Elizabeth Sumi; http://lattes.cnpq.br/7240314827308306; BASTOS, Gilmara de Nazareth Tavares; http://lattes.cnpq.br/2487879058181806
Chronic injuries affect a large portion of society, treatment for these patients has high financial costs and a result that is not satisfactory. Thus, the objective of this work was to investigate whether ethanolic extracts from the stem, petiole and leaf of Montrichardia linifera (Arruda) Schott have healing activity in vitro. For that, the identification of substance classes of the extracts was carried out by HPTLC, the analyzes of: cytotoxicity, in vitro healing, hematoxylin and eosin morphology and immunomarking for BrdU was also performed. This demonstrated the antioxidant activity and the presence of terpenes in the three extracts, and the presence of flavonoids and phenols in the leaf extract. A serial curve was performed with concentrations of 100 to 0.19 μg / ml of the extracts of the stem, petiole and leaf, in times of 24, 48 and 72h, and it did'n present cytotoxicity. From the cytotoxicity test, the concentrations of 0.78, 0.39; 0.19 μg/ml of the three extracts were chosen for the next tests. Thus, the control group in 6, 12 and 24 hours showed a lesion area of 82.08 ± 12.13, 56.14 ± 15.75, 34.34 ± 10.12%, respectively; while the extract of the stem showed lesion area, in the time of 6h, of 66.108 ± 23.85, 66.10 ± 13.13, 64.81 ± 20.42%, respectively; in 12h, 38.86 ± 20.66, 40.45 ± 14.64, 32.29 ± 16.62, respectively; in 24h, 13.48 ± 11.20, 10.67 ± 7.94, 10.15 ± 7.35%, respectively. The petiole extract showed a lesion area, in 6h, 74.02 ± 15.16%, 80.32 ± 22.50%, 75.56 ± 20.09%, respectively; at 12h, 38.86 ± 20.66, 46.79 ± 12.46, 40.98 ± 5.45%, respectively; in 24h, 13.48 ± 11.21, 27.33 ± 13.86, 12.40 ± 7.72%, respectively. The leaf extract, on the other hand, showed a lesion area, in the time of 6h, 73.08 ± 21.35, 72.91 ± 18.19, 67.84 ± 17.89%, respectively; in 12h, 48.76 ± 21.17, 48.02 ± 17.30, 44.54 ± 18.70%, respectively, in 24h, 24.59 ± 14.58, 26.07 ± 16 , 73, 23.75 ± 15.76%, respectively. There was no significant morphological change in hematoxylin and eosin staining. In the quantification of positive BrdU cells, the control group showed an average of 19.778 ± 3.80, while the groups treated with the extracts at concentrations of 0.78, 0.39, 0.19 μg/ml, for the extract of stem, demonstrated mean of 20.222 ± 1.855, 37.889 ± 7.407, 29.778 ± 4.521 positive BrdU cells, respectively, for petiole extract, mean of 20.222 ± 2.587, 20.444 ± 5.077, 24.889 ± 3.551 positive BrdU cells, respectively; for leaf extract, mean of 20,556 ± 3,504, 23,778 ± 5,974, 22,889 ± 3,1798 positive BrdU cells, respectively. Therefore, Montrichardia linifera stem and petiole extract, in small concentrations, demonstrated wound healing activity in vitro.
Acesso aberto (Open Access)
Avaliação in vitro do potencial genotóxico e citotóxico do extrato do açaí (Euterpe oleracea) clarificado sobre a linhagem celular AGP01 (câncer gástrico)
(Universidade Federal do Pará, 2024-01) SANTOS, Thiago Souza; BAHIA, Marcelo de Oliveira; http://lattes.cnpq.br/3219037174956649; BURBANO, Rommel Mario Rodríguez; http://lattes.cnpq.br/4362051219348099; https://orcid.org/0000-0002-4872-234X
Açaí (Euterpe oleracea MART) is a fruit of great importance for the Amazon region in nutritional, cultural and socioeconomic terms. In recent years, açaí has been the subject of several studies due to its beneficial properties for health, including effects against tumor cells. Therefore, the present work aimed to evaluate in vitro the genotoxic and cytotoxic effects of the clarified extract of açaí juice in a human metastatic gastric cancer cell line (AGP01 cells). For comparison purposes, a non-transformed cell line of African green monkey renal epithelial cells (VERO cells) was used. The viability assay by resazurin reduction, the comet assay, the determination of cell death by differential fluorescent dyes and the wound healing migration assay were performed. A reduction in viability was observed only in the AGP01 line within 72h. There was no genotoxic damage or cell death (through apoptosis or necrosis) in any of the cell lines. However, açaí extract induced motility reduction in both cell lines. The reduction in cell viability and the induction of the anti-migratory effect in the AGP01 cell line opens perspectives for exploring the potential of Euterpe oleracea as an adjuvant in the treatment of gastric cancer.
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/0000-0002-4872-234X
Biodegradable 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.
Acesso aberto (Open Access)
Impacto da busca ativa especializada no diagnóstico da hanseníase: avaliação longitudinal e comparativa de aspectos clínicos e laboratoriais em áreas endêmicas no Pará e no Maranhão
(Universidade Federal do Pará, 2024-08) COSTA, Izabelle Laissa Viana; COSTA, Patrícia Fagundes; http://lattes.cnpq.br/6487407290759330; SALGADO, Claudio Guedes; http://lattes.cnpq.br/2310734509396125
Leprosy is a disease that represents a significant public health problem in various parts of the world, including Brazil. To improve epidemiological data, active case finding activities and longitudinal research represent a transformative approach to disease control. In this context, the present study aimed to evaluate and compare the clinical and laboratory aspects of patients with leprosy, their contacts, and schoolchildren over a one-year period in endemic areas in Pará and Maranhão. To achieve this, a longitudinal study was conducted, characterized by active case finding activities in Imperatriz-MA, São Luís-MA, and Marituba-PA, where registered leprosy cases in the Notifiable Diseases Information System (SINAN), their contacts, and school-aged children were evaluated. Participants underwent neurodermatological evaluation and blood collection for the titration of IgM anti-PGL-I antibodies, as well as intradermal scraping of the earlobes and elbows for bacilloscopy and qPCR. After one year, in 2023, participants from the municipalities of Imperatriz and São Luís were re-evaluated, and new participants were included. Among 522 individuals included in this study, 135/522 (25.9%) were clinically and/or laboratorially re-evaluated in 2023, and 387/522 (74.1%) were evaluated exclusively in 2022 or 2023. In 2022, new cases were identified among 66/221 (29.9%) contacts and 23/195 (11.8%) schoolchildren. Additionally, 9/34 (26.5%) relapses and 2/34 (5.9%) patients with therapeutic insufficiency or failure were diagnosed among index cases. In 2023, new cases were observed among 70/126 (55.5%) contacts and 10/29 (34.4%) schoolchildren. Furthermore, 7/12 (58.3%) relapses and 1/12 (8.3%) patients with therapeutic insufficiency or failure were diagnosed among index cases. In the neurodermatological evaluation, among schoolchildren and contacts who were re-evaluated, individuals with an altered superficial fibular nerve were found to be 4.3 times more likely to be in the disease case group (p < 0.05; 95% CI = 1.58- 12.74; OR = 4.32). The bacilloscopy test identified the etiological agent in 7/222 evaluated individuals (3.1%), with 4/7 (57.1%) being among individuals with a prior diagnosis of leprosy. Regarding the serological analysis of re-evaluated individuals, seropositivity was observed in 26/106 (24.5%) individuals in 2022, and 7/106 (6.6%) in 2023, a statistically significant decrease (p < 0.05). A high positivity rate for the qPCR technique was observed, including 9/10 (90%) relapses, 55/88 (62.8%) new cases, and 43/151 (48.3%) contacts. These data highlight a concerning scenario characterized by a high number of hidden leprosy cases in the analyzed regions, and a significant increase in diagnosis rates after one year of follow-up in the communities, underscoring the importance of longitudinal research and the implementation of different diagnostic and monitoring techniques for a better understanding of leprosy and its outcomes in endemic areas.
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/3032008039259369
Introduction. 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.
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/2310734509396125
Leprosy 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.
Acesso aberto (Open Access)
Pesquisa de hanseníase em doadores de sangue
(Universidade Federal do Pará, 2024-11) JORGE, Erika Vanessa Oliveira; PALMEIRA, Mauricio Koury; http://lattes.cnpq.br/2785104508455046; SALGADO, Claudio Guedes; http://lattes.cnpq.br/2310734509396125
Hansen’s disease (HD) is an infectious disease with active transmission in endemic areas such as Brazil, which accounted for over 90% of the new HD in the Americas in 2021, and the second highest in the global scale. Clinically is characterized by the appearance of nerve or skin lesions with altered sensitivity, that in advanced cases, can cause deformities and physical disabilities. Its transmission occurs mainly through Mycobacterium leprae, through respiratory droplets of sick people, and has a prolonged incubation period. The diagnosis of leprosy is clinical, with multidrug treatment PQT (polychemotherapy) being crucial to avoid the chain of disease transmission. Suspected cases should be attended by a qualified professional in basic health units or active case finding campaigns. Although leprosy patient is considered definitively unfit for blood donation process, according to Consolidation regulation nº 5, of October 3, 2017, leprosy investigation occurs only through a clinical interview, without laboratory evaluation. At Hemocenter from Pará, 500 donors were selected for the study and blood was collected for serological investigation of anti-PGL-I antibodies. Of the selected donors, 4% (20/500) had positive serological results greater than or equal to 0,750 optical density among only eight agreed to be clinically examined and underwent other laboratory tests: bacilloscopy and qPCR. Among donors with clinical evaluation, more than half were diagnosed with leprosy, 62.5% (5/8), with the following cases: one individual with the primarily neural clinical form, three with borderline-tuberculoid, one lepromatous. of peripheral blood, the presence of the bacillus in two individuals was confirmed, suggesting a possible route of transmission of the disease. We emphasize that the prevalence of subclinical leprosy infection due to its etiological agent among the study population is very high, but compatible with the hidden prevalence already recorded in the state of Pará.

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