Dissertações em Neurociências e Biologia Celular (Mestrado) - PPGNBC/ICB

URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/2375

O Mestrado 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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Ação da ciclosporina A na via de ativação do fator de crescimento de nervo (NGF) em células neurais do SNP
(Universidade Federal do Pará, 2016-08-26) JESUS, Jessica Batista de; SENA, Chubert Bernardo Castro de; http://lattes.cnpq.br/8620752020290438; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978
A is an immunosuppressive drug with known action on T cells of the immune system used in organ transplantation and autoimmune diseases. In the nervous system, cyclosporin A acts by inhibiting the action of Calcineurin, an important second messenger from pathway of signal transduction Nerve Growth Factor (NGF), resulting in hyperphosphorylation of the nuclear factor of activated T cells (NFAT), and downregulation of NGF, TrkA and other factors that participating in this pathway. The NFAT1-4 family are dependent isoforms of calcineurin, while NFAT5 isoform is independent. It has been demonstrated the neuroprotective role of Cyclosporin A via calcineurin dependent or independent. In this study, we evaluate the action of Cyclosporine A in the PNS system, that could be associated with levels of NGF, TrkA and an independent of calcineurin transcription factor (NFAT5) that interplay the plasticity of neuronal cells derived from Dorsal root ganglia (DRG) maintained in cultures. We use E10 DRG cultures supplemented with medium conditioned E9 Retinal treated with Cyclosporin A for 48 and 72 hours. Cultures enriched neurons were confirmed by calcium imaging method. The action of Cyclosporine A in the neuritogenesis was assessed by bright field microscopy, expression of NGF, TrkA and NFAT5 was performed by RT-PCR, intracellular accumulation of NGF was evaluated by immunofluorescence and the presence of TrkA in neurons. The viability test of the cultures treated or not with the concentrations of 1-40μM Cyclosporine A was performed by MTT method. The results show an increase of NGF levels in mixed cultures, and TrkA receptor and NFAT5 in cultures enriched in neurons following treatment with cyclosporine A. Given the importance of NGF pathway in the development and maintenance of the SNP, the use of Cyclosporin A have activity in the peripheral nervous system cells, which might be used in the clinic with new target for new therapies.
Acesso aberto (Open Access)
Ação da hidroxicloroquina sobre neurônios da retina de embrião de galinha
(Universidade Federal do Pará, 2017-03-22) ROSÁRIO, Aldanete Santos; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978
Hydroxychloroquine (HCQ) is currently used in the treatment of malaria and autoimmune diseases and others therapeutic purposes. However, this drug is known to cause side effects, including producing visual disturbances, which may be irreversible. The mechanisms that produce these visual disorders are not completely known. HCQ - related retinal toxicity may be due to high metabolic rate, being very susceptible to the action of xenobiotics and oxidative damages. Thus, this work aims to evaluate the effects of the HCQ on retinal cells, as well as their possible mechanisms of cytotoxicity. The model used in this work was of cultures of retina cells from chicken embryo. To evaluate cell viability, mitochondrial activity was measured by MTT. The lysosomal function was evaluated by the incorporation rate of the neutral red dye. The levels of reactive species of general oxygen and superoxide anion were evaluated by the CellROX probe and by Nitro Blue Tetrazolium (NBT) and total glutathione levels were quantified using the Ellman reagent. Viability was tested in mixed cultures (glia and neurons) or enriched cultures of neurons and glia after treatment with HCQ and compared with chloroquine (CQ). Cells were exposed to concentrations of 25μM, 50μM and 75μM for 24 hours. The results show that mixed cultures treated with CQ presented a reduction in viability of 36 and 61% at concentrations of 50μM and 75μM, respectively, whereas HCQ did not alter viability at any of the concentrations tested. However, when cultures enriched with glial cells were exposed to HCQ for 24 hours, the concentration of 75μM had a small reduction in cell viability, while that the reduction in neuronal cells was of 20, 33 and 56% at the concentrations of 25μM, 50μM and 75μM, respectively. Even a shorter treatment time (6 hours) there was loss of viability in retinal neurons. The incorporation of neutral red supravital dye was also altered in neuronal cultures treated with HCQ for 24 hours, with reduction of 19 and 32%, compared to the control for the concentrations of 50μM and 75μM, respectively. HCQ significantly reduced the levels of reactive oxygen species produced by the neuronal cells, mainly superoxide anion, 43, 52 and 61% for the concentrations of 25μM, 50μM and 75μM of HCQ in 24 hours of treatment, respectively. In concentrations of 50μM and 75μM of HCQ for 24 for hours, the levels of total glutathione in neuronal cells presented a reduction of 37 and 53%, respectively. When the glial cell conditioned medium was used in neuronal cells for 6 hours after treatment with HCQ, it completely reversed the drug-induced cytotoxicity. When total glutathione levels were measured in culture of glia treated with HCQ for 24 hours no changes were observed. These results suggest cytotoxic action of CQ in mixed culture of chicken embryo retina cells which is not observed in HCQ treatment. However, HCQ showed cytotoxic action when cells are cultured separately, mainly on neurons, which is reversed by some factor released by glial cells in the extracellular environment, and glutathione is a possible candidate to exert this neuroprotective function.
Acesso aberto (Open Access)
Ação do alcaloide (+)-filantidina sobre o protozoário Leishmania (Leishmania) amazonensis e a célula hospedeira
(Universidade Federal do Pará, 2014-08-14) MORAES, Lienne Silveira de; SILVA, Edilene Oliveira da; http://lattes.cnpq.br/7410116802190343
Leishmaniasis is an antropozoonotic disease caused by parasites of the genus Leishmania. These parasites proliferate primarily within macrophages of mammals and are responsible for promoting a variety of clinical manifestations, such as cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL). The treatment available is chemotherapy, but is limited by toxicity and requires a long term treatment. The study of natural products from plants such as antileishmanial agent currently plays an important role in the search for new drugs for the treatment of leishmaniasis. (+)-phylantidine, is an alkaloid extracted from stem of Margaritaria nobilis of the family Phyllanthaceae. The aim of this study is evaluated the effects of (+)-phylantidine on promastigotes forms of Leishmania (Leishmania) amazonensis and host cell. Antiproliferative activity of promastigotes forms was observed when parasites were treated with 50, 100 e 200 μg/mL of alkaloid for 96 hours, with reduction of 73.75%, 82.50% and 88.75%, respectively when compared with non-treated parasites. In the period of 96 hours it was observed an IC50 of 56.34 μg/mL. Amphotericin B was used as reference drug and reduction of 100% in parasites treated with 0.1 μg/mL was observed after 96 hours. Treatment with the alkaloid promoted important changes in promastigotes that were observed by scanning and transmission electron microscopy. Alterations in cell body, flagellum, kinetoplast, mitochondria, rosette formation, presence of electrodense vesicles suggestive of lipid body and increase in structures like acidocalcisssomes were observed. In the host cell no cytotoxic effect was observed in the macrophages treated with the alkaloid and analysis by scanning electron microscopy showed that the alkaloid promoted an increase in the number of cytoplasmic projections, increased cell volume and spreading. Thus, these results demonstrate that (+)-phylantidine was effective in reducing the growth of the protozoa, without citotoxy effect which may represent a promising natural alternative source for the treatment of leishmaniasis.
Acesso aberto (Open Access)
Alterações de expressão gênica na linhagem de glioblastoma humano U87 após exposição ao MeHg e HgCl2
(Universidade Federal do Pará, 2016-12-02) GOMES, Bruna Puty Silva; OLIVEIRA, Edivaldo Herculano Correa de; http://lattes.cnpq.br/0094007714707651; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468
The organic and inorganic forms of mercury have been pointed as important contaminants in several world regions due to its toxicological characteristics. Various studies have reported that the intoxication by methylmercury (MeHg) and mercury chloride (HgCl2) can lead to central nervous system impairment. It is generally agreed that glial cells are important for the mechanisms responsible for cellular protection against the damages caused by the mercury. However, little is known about the influence of the mercury in the cells genome. Hence, in the present study we did a complete mapping of the humam glial cells genetic network after mercury exposition with the aim to indentify the possible genetic alterations that occurred via the organic and inorganic forms of mercury. Our results demonstrated that U87 lineage cells are more sensitive to MeHg exposition when compared with HgCl2 exposition. Using an analysis of the concentration curves the LC50 was obtained from 28.8μM and 10,68μM after 4h and 24h exposition to MeHg and a LC50 of 92.25μM and 62.75μM after the same time periods exposition to HgCl2. Regarding the genic pool, our results have shown that both metal forms led to alterations in the genic dosage where the MeHg exposition was highly influenced by the concentration and time, whereas the HgCl2 exposition seemed have been strongly influenced by the exposition time. In total there were 205 indentified genes with a lower genic dosage and 188 genes with elevated expression, (Fold change > 5) after 4h exposition and 5μM of MeHg, and 204 down-regulated genes; and 180 up-regulated genes after HgCl2 exposition in the same concentration. The analysis after 24h exposition showed 90 down-regulated genes and 3 up-regulated genes after 1μM of MeHg; 116 genes were down-regulated and 66 genes were up-regulated after a 10μM exposition of MeHg. As for the HgCl2, there were 98 down-regulated genes and 73 up-regulated genes for the groups exposed to 5μM of HgCl2; 326 down-regulated genes and 66 up-regulated genes for the groups exposed to 62,75μM of HgCl2. Our dataset suggests that both mercurial forms are able to alter the cell genetic expression profile thus interfering in important signaling paths prone to gives rise to biochemical impairments and glial cells phenotypes.
Acesso aberto (Open Access)
Alterações morfo-funcionais em córtex isquêmico de animais tratados com transplante autólogo de células mononucleares da medula óssea
(Universidade Federal do Pará, 2015-10-08) BARBOSA JUNIOR, Mário Santos; PEREIRA JÚNIOR, Antônio; http://lattes.cnpq.br/1402289786010170; BAHIA, Carlomagno Pacheco; http://lattes.cnpq.br/0910507988777644
Statistical data show stroke as the second leading cause of death and leading cause of disability among all other diseases in the world. The ischemic stroke (ischemic stroke) accounts for about 87% of incidence of strokes. In ischemic stroke, inflammation acts in restraint of infarction caused by ischemic stroke, and on the other hand the intensity of the inflammatory response in neurodegeneration and consequently influence the functional loss. The autologous cell therapy, mononuclear bone marrow cells, promotes modulation in neuroinflammation, being timely during an ischemic event for reduction of tissue loss and functional. In the present study, we used an experimental model of focal ischemic stroke to assess morphological and functional effects of autologous implant mononucleres bone marrow cells (CMMOs) on the morphological and functional changes related to ischemic stroke. We demonstrate in this study that the autologous BM-MNC in acute or acute and subacute periods of ischemic event, promoted neuroprotection and inflammatory modulation able to rebound in preservation and functional recovery in specific activities. We also show that the treatment enhanced in subacute period, the ischemic event, was able to promote increase in morphological and functional improvements promoted by autologous transplantation in acute period.
Acesso aberto (Open Access)
Análise citogenética como bioindicador para pacientes com diagnóstico sugestivo de Alzheimer
(Universidade Federal do Pará, 2013-08-02) NEGRÃO, Igor Patrick Ramos; BAHIA, Carlomagno Pacheco; http://lattes.cnpq.br/0910507988777644; PEREIRA JÚNIOR, Antônio; http://lattes.cnpq.br/1402289786010170
Alzheimer's disease (AD) is a neurodegenerative disease that causes neuronal death and consequent progressive loss of cognitive functions, reducing the capacity for work, interfering with social relationships and behavior of the patient. Among the diseases that cause dementia, AD is the most frequent nature of the vascular a ratio of 4:1, respectively. In addition to the pharmacological therapies, diagnostic methods assist in the early identification of the disease by helping the pretreatment, thus reduced disease progression. Currently cytogenetic studies have demonstrated chromosomal abnormalities in individuals with AD and may aid in the diagnosis of disease. The aim of this study was to investigate the potential of karyotype analysis of peripheral blood lymphocytes as a diagnostic biomarker of Alzheimer's disease. For this work, we used two groups of women aged 65 or more, one group (10) suffering from AD and other normal group (10). Each subject was submitted to the socioeconomic survey, a cognitive screening test (MMSE) and the Venous blood lymphocyte culture and chromosome analysis. Our results demonstrate that the group of women with AD showed high rate of monosomy and trisomy compared to normal women. Through the study of history via questionnaire, we found the lifestyle of both groups. Compared the relationship of chromosomal abnormalities with the cognitive level of the AD group, we evidenced an inverse trend between the number of monosomy / trisomy and cognitive performance. Another aspect of our analysis was the role of each chromosome linked to AD. Chromosomes 1, 14 and 21 showed no trisomy and verify the frequency of monosomy, each chromosome has frequency below 3 % of aneuploidy, i.e., the chromosomes studied did not have a great importance in chromosomal alterations found in the study.
Acesso aberto (Open Access)
Análise citogenética comparativa em espécies de morcegos da subfamília phyllostominae (chiroptera-phyllostomidae) por citogenética clássica e hibridização in situ Flourescente (fish)
(Universidade Federal do Pará, 2011-03-29) SILVA, Natalia Karina Nascimento da; PIECZARKA, Julio Cesar; http://lattes.cnpq.br/6644368250823351
Bats are a highly distributed and diversified group.The diversity of feeding habits makes the Order Chiroptera one of the highest successes among mammals, being very important, because of these habits, on the control of insects, on pollination, and on dispersion of seeds of many vegetables. The family Phyllostomidae is the third bigger family on number of species into the Order Chiroptera. Among the neotropical ones, this family is the most numerous, being found in the rainforests of South America, especially in the Amazon region, where there is the highest diversity of bats in the World. In the present work it was analyzed cytogenetically a sample of three species of the subfamily Phyllostominae: Chrotopterus auritus, Trachops cirrhosus and Vampyrum spectrum collected in the Pará and Amazon states. The chromosomal data obtained for Chrotopterus auritus (2n = 28 e NF = 52) and Trachops cirrhosus (2n = 30, FN = 56) are in agreement with the ones described in the literature. For Vampyrum spectrum (2n=30 NF=56) we described for the fist time the banding patterns and FISH (Fluorescent in situ Hybridization). The C-banding technique demonstrated a pericentric pattern of distribution of the centromeric heterochromatin in the three species here studied. The FISH with telomeric DNA probes shown only distal hybridizations in all chromosomes of the three species, while the 18S rDNA proble confirmed the location of the NOR observed by Ag-NOR staining, in the long arm of pair 2 Chrotopterus auritus, in the pair 11 of Trachops cirrhosus and in the long arm of the pair 1 of Vampyrum spectrum. The comparative analysis among the species suggests an extensive chromosomal differentiation, with few chromosome pairs being shared among the three genera. Five whole chromosome pairs were conserved without any rearrangement after the divergence of the three lineages. The comparison among the species shows that C. auritus and V. spectrum have more shared pairs between them than with T. cirrhosus. Our results support the phylogenetic association between C. auritus and V. spectrum and suggest the association of T. cirrhosus with the genus Phyllostomus.
Acesso aberto (Open Access)
Análise da proteção de citocinas após exposição celular in vitro com os antígenos ML2478 e ML0840 do Mycobacterium leprae
(Universidade Federal do Pará, 2019-09) MESSIAS, Ana Caroline Cunha; SALGADO, Claudio Guedes; http://lattes.cnpq.br/2310734509396125; http://orcid.org/0000-0003-3961-7764
Diagnosis of oligosymptomatic leprosy cases may enable interventions to be performed before the onset of physical disabilities. However, because the diagnosis is still essentially clinical and the disease progresses slowly, there is difficulty in recognizing these cases, since the lesions are discreets and with subtle changes in sensitivity. Most of the time patients are diagnosed when they already have obvious clinical characteristics and/or physical disabilities. Thus, is necessary to develop laboratory tools that help in the early diagnosis of the disease. The cell immunity assay Whole Blood Assay (WBA) is a low-cost, easy-to-perform technique that provides conditions for antigen screening and is favored in areas where leprosy is endemic and may facilitate incorporation of a test into sites with less access to sophisticated laboratories. The objective of this study was to evaluate the cellular immune response after in vitro exposure of peripheral blood to Mycobacterium leprae antigens ML2478 and ML0840. Eighty-seven individuals were selected for quantitation the cytokines of Interferon-γ (IFN-γ), Interleukin (IL)-10, IL-17 and Transforming Growth Factor-β1 after exposure with specific M. leprae antigens by WBA for 24 hours. A total of 47 leprosy cases were evaluated distributed in: 6 tuberculoid and 14 borderline tuberculoid, 13 borderline lepromatous leprosy, 6 lepromatous leprosy; and 8 schoolchildren diagnosed with leprosy during the group active search strategy (oligosymptomatic cases in the clinical forms: 1 primary neural, 1 undetermined, 6 borderline tuberculoid). The remaining 47 individuals corresponded to 20 contacts, 13 healthy schoolchildren and 7 individuals with other skin diseases. The analysis of cytokines suggests the balance between IFN-γ and IL-10 may indicate individuals who are progressing to the Th2 pole. IL-17 and TGF-β1 may be used to follow-up individuals with similar response to leprosy cases. The production of IFN-γ, IL-10, IL-17 and TGF-β1 cytokines by stimulation with proteins ML2478 and ML0840 did not differ between healthy students and case students. And the cytokine IL-17 demonstrated higher production in cases attended at URE than in case students and individuals in control groups.
Acesso aberto (Open Access)
Análise in vitro do potencial antitumoral do conjugado LDE/Paclitaxel comparado à formulação do comercial Taxol sobre linhagem celular C6 de glioblastoma de rato
(Universidade Federal do Pará, 2022-09) ANJOS, Ana Carolina Brito dos Anjos; FRANCO, Edna Cristina Santos; http://lattes.cnpq.br/5939607544965550; https://orcid.org/0000-0003-2909-949X; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Glioblastoma, also known as grade IV astrocytoma, is one of the most common and aggressive types of tumors in the central nervous system. Among the characteristics of this type of tumor, the following stand out: infiltration of isolated tumor cells in normal brain tissue, cell proliferation, angiogenesis and intense necrosis. Currently, the main therapeutic approach consists of surgical resection followed by radiotherapy and chemotherapy. However, in most cases, the tumor is not well defined, spreading through the brain region, which makes it difficult to fully resection. In addition, the removal of tissue from this region can leave several sequels. Consequently, patients have high rates of recurrence and low rates of survival. Another problem in the treatment of this type of tumor is due to the lining of the blood-brain barrier that restricts the entry of molecules and substances, including drugs. Thus, this project aims to analyze the antineoplastic effects of the association of a nanoparticle called LDE with a structure similar to low-density lipoprotein (LDL) that will act as a carrier of the drug paclitaxel (PTX), commercially known as Taxol®, it is a chemotherapeutic drug whose cell antiproliferative action has been proven in the treatment of other types of cancer, such as breast and refractory ovarian cancers. For this purpose, the mouse glioblastoma cell line C6 was used for performing in vitro analysis regarding the effects of these treatments on aspects of viability, cytotoxicity and cell death by apoptosis, using the ApoTox-GloTM Triplex Assay kit (Promega Corporation), which performs the three previously mentioned analyses, sequentially. To evaluate growth and drug effect on PTX and LDE/PTX treatment groups, approximately 1x106 cells were cultured in 96-well microplates at concentrations of 0.01; 0.1; 1 and 10 μM in the times of 24h, 48h and 72h. The control was not exposed to the compounds, containing only DMEM culture medium. Results obtained after treatments with PTX and LDE/PTX were expressed as mean ± standard deviation and analyzed by one-way (cytotoxicity) and two-way (viability and apoptosis) ANOVA, followed by Tukey's post hoc test. Differences were considered significant when p ˂ 0.05.
Acesso aberto (Open Access)
Análise morfométrica do sistema auditivo periférico da preguiça (Bradypus variegatus)
(Universidade Federal do Pará, 2010-08-27) SOUSA, Pêssi Socorro Lima de; FRANCO, Edna Cristina Santos; http://lattes.cnpq.br/5939607544965550; PEREIRA JÚNIOR, Antônio; http://lattes.cnpq.br/1402289786010170
The mammalian super order Xenarthra is composed of about 31 extant species of armadillos, anteaters and sloths. The tree sloths belong to two genera, Choloepus and Bradypus, which diverged close to 40 million years ago. The similarities between the two taxa, such as the presence of green algae in the fur and the suspensory locomotor ability, are remarkable examples of convergent evolution. The exact location of the xenarthran lineage within the mammalian phylogenetic tree isn’t completely understood yet, with some recent rearrangements of the placental mammal family tree considering xenarthrans to be either most closely related to Afrotheria (that includes shrews, aardvarks, seacows and elephants), or Boreoeutheria (that includes primates, rodents, carnivorans and ungulates). The aim of present work is to describe for the first time the morphological features of both the middle and the inner ear of Bradypus variegatus and compare them to other placental mammals whose data is available in the literature. We used 13 mature postmortem specimens (males and females) and 15 skulls from the collection of the Museu Paraense Emílio Goeldi. Than measurements, techniques were used optical microscopy, scanning electron microscopy and computed tomography. Within the sloths’ phylogenetic tree, the genus Bradypus is positioned as the sister-taxon to all other sloths. Our results show that the morphology of the middle and inner ears of Bradypus variegatus are similar to other mammals with data published in the literature and they present allometric scalation.
Acesso aberto (Open Access)
Análise quantitativa de neurônios imunomarcados para parvalbumina no hipocampo e núcleo magnocelular do istmo em Actitis macularius no período de invernada
(Universidade Federal do Pará, 2020-02) GUERREIRO, Luma Cristina Ferreira; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286; DINIZ, Daniel Guerreiro; http://lattes.cnpq.br/3269424921125406; https://orcid.org/0000-0001-7369-2165
It is already known that parvalbumin (PV) neurons have their number modified in face of social, multisensory and cognitive stimuli, both in mammals and birds. However, nothing is known about its plasticity in long-distance migratory shorebirds during wintering period. Here we investigated in four distinct temporal windows of the wintering period, the plasticity of PV neurons of two brain areas of the spotted sandpiper (Actitis macularius) which includes in its migratory journey multiple stopovers for feeding and resting. We used PV as a marker of a subpopulation of inhibitory neurons and count them in the hippocampal formation (HF) and magnocellular nucleus of tectal isthmus (IMC). Based on previous evidence that HF is involved in learning and memory and social interaction, and IMC is essential for control of head and neck and eyes movements, we tested the hypothesis that PV neurons would increase in HF and remain unchanged in IMC. For this, we used the optical fractionator to estimate cell number. Brains were processed for PV immunostaining, followed by estimates of the number of PV neurons of the areas of interest. As compared with migratory rest 1, PV neurons estimates showed significant increase in the hippocampal formation of premigration group. We suggest that parvalbuminergic neurons proliferation is part of the adaptive changes of the hippocampal circuits involved with the migratory process back to the reproductive niches in north hemisphere.
Acesso aberto (Open Access)
Análises dos genes TP53, PTEN, IDH1 e IDH2 em tumores não gliais do sistema nervoso humano
(Universidade Federal do Pará, 2016-06-17) LOPES, Cleiton Mendes; ANSELMO, Nilson Praia; http://lattes.cnpq.br/6518287721873199
Despite the considerable incidence, studies of genetic changes in gene TP53, PTEN, IDH2 and IDH1, in not glial tumors are rare and, in some cases, nonexistent. Glial tumors are usually not classified as benign and rarely evolve to malignancy, with different classifications, effects and locations. The tumor suppressor genes and response to DNA damage, TP53 and PTEN are among the most commonly mutated gene in human tumors. The genes IDH1 and IDH2 are involved in cell metabolism and also were frequently found mutated in gliomas, melanomas and leukemias, currently being considered as good markers for gliomas. Genetic analyzes were performed in those genes, in order to verify that are associated with the etiology and/or progression of non-glial tumors of Human Nervous System (HNS). SSCPPCR techniques for the amplification of the region of interest and mutational screening of samples for subsequent sequencing were used. We analyzed 37 samples of non-glial tumors (14 schwannomas, meningiomas 3, 4 Medulloblastomas, 2 neurocytomas and 14 metastases of Central Nervous System (CNS). Only the gene IDH1 polymorphisms presented on the SSCP 12 (32.4%) samples, and then subjected to sequencing. However, sequencing reactions were satisfactory in only 5 samples, of the polymorphic, (1 metastasis, meningioma 1 and 3 schwannomas). Analysis of these samples have identified 5 different mutations, one present in all, one transversion T → A in codon 106 of exon 4 of the IDH1 gene resulting in amino acid substitution of threonine by serine. Were also identified other mutations in noncoding regions (intron 4) of gene IDH1 in two of these samples. The mutations found in our study had not yet been reported in the literature. Our results indicate the participation the gene IDH1 in the pathogenesis of these tumors.
Acesso aberto (Open Access)
Atividade antiinflamatória e neuroprotetora da Edaravona no córtex sensóriomotor primário de ratos adultos submetidos à isquemia focal experimental
(Universidade Federal do Pará, 2014-02-12) ARAÚJO, Sanderson Corrêa; BORGES, Rosivaldo dos Santos; http://lattes.cnpq.br/4783661132100859; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Stroke is a neural disorder originated from blood flow decreasing or interruption, making inadequate energy supply in the region, thus promoting tissue damage. The stroke can be divided in hemorragic or ischemic. The ischemic stroke is more prevalent and can occur through thrombosis or embolism. The ischemic pathology has multiple interrelated events like excitotoxicity, peri-infarct depolarization, oxidative and nitrosative stress, inflammation and apoptosis. An element of fundamental importance in ischemic pathology is the microglial cell, whose activity is closely linked to the progression of environment harm. A therapeutic alternative in the treatment of stroke is a pyrazolone called Edaravone. This study evaluated the neuroprotective effect of Edaravone dose of 3mg/kg in primary sensorymotor cortex after focal ischemic lesion. Edaravone treated animals (N = 10) and animals treated with saline solution (N = 10) in the survival time of 1 and 7 days after the ischemic event was evaluated. Treatment whith edaravone showed by histopathological analysis with cresyl violet a reduction of 49% and 66% in infarct size in animals in survival time 1 and 7 days respectively. Immunohistochemistry studies for microglia/macrophages assets (ED1+) demonstrated a reduction in the presence of ED1+ cells in 35% and 41% survival times for 1 and 7 days, respectively. Neutrophils (MBS-1+) were reduced to 64% only in animals with survival times a day. Harmful patterns were assessed qualitatively and quantitatively. Data was tested by ANOVA with Tukey post hoc test. Differences were considered significant at p < 0,05.
Acesso aberto (Open Access)
Atividade leishmanicida do extrato da raiz de Physalis angulata e sua ação na célula hospedeira
(Universidade Federal do Pará, 2013-05-23) SILVA, Raquel Raick Pereira da; SILVA, Edilene Oliveira da; http://lattes.cnpq.br/7410116802190343
Leishmaniasis is an infectious disease caused by various species of the protozoan parasites of the Leishmania genus. The chemotherapy is the only effective treatment for the disease, but these drugs are, in general, toxics and requires a longer treatment period. Natural products have been used as traditional medicine and offer new perspectives and represent an important source of new antileishmanial agents. Thus, it is of great importance to assess the effects of the aqueous extract of the root of Physalis angulata, a plant widely used in popular medicine, in promastigotes and amastigotes of Leishmania (Leishmania) amazonensis and its effect on the host cell. Physalins D, E, F and G were found present, for the first time, in the P. angulata roots using liquid chromatography/mass spectrometry analysis. Antiproliferative activity and a dose-dependent inhibition of promastigote growth 74.1% and 99.8 % (IC50 35.5 μg/mL), and intracellular amastigotes 70.6% and 70.8% (IC50 32.2 μg/mL) was observed when parasites were treated with 50 and 100 μg/ mL of extract, respectively. The analysis of the microbicidal activity of host cell infected, with L. amazonensis demonstrated that extract is able to reverse the effect caused by the parasite to inhibit the production of reactive oxygen species. This growth inhibition was associated with several morphological alterations assessed by optical microscopy, transmission electron microscopy and scanning such as alteration on cell division, especially in the phase of cytokinesis, alteration in flagellar membrane, in flagellar pocket and duplication of kinetoplast DNA. Already by flow cytometry was possible to confirm that the treatment induced a phosphatidylserine exposure and decreased cell volume of promastigotes treated. In the host cell were observed cytoskeleton alterations, high number of cytoplasmatic projections, increase of cytoplasm, vacuoles and spreading ability. No cytotoxicity towards macrophages was observed. We have demonstrated that aqueous extract effectively promotes antileishmanial activity and clearly demonstrate the induction of apoptosis and ultrastructural alterations in Leishmania parasites. Thus, aqueous extract may represent a promising natural alternative source for a new antileishmanial agent.
Acesso aberto (Open Access)
Avaliação antitumoral de amidas graxas derivadas de triglicerídeos de óleo de andiroba (Carapa guianensis aublet) em linhagem celular de glioma in vitro
(Universidade Federal do Pará, 2022-06-26) SILVA, Nágila Monteiro da; OLIVEIRA, Fábio Rodrigues de; http://lattes.cnpq.br/4538804050936779; https://orcid.org/0000-0003-2761-3440; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978; https://orcid.org/0000-0003-3647-9124
Glioma is a rare type of tumour, which acts on Nervous System in a very aggressive way, presents problems in its diagnosis, low effective treatments and survival time less than one year after diagnosis. Due to factors such as intratumoral cell variability, inefficient chemotherapy drugs, adaptive resistance development to the drugs and tumour recurrence after resection, the development of new drugs becomes necessary. In this sense, molecules analogues to endocannabinoids such as fatty amides are a good alternative, since scientific literature shows that they can act as antitumor agents through the interaction with the endocannabinoid system, which modulates many metabolic pathways related to cancer. In this work, two fatty amides synthetized from andiroba (Carapa guianensis aublet) using lipase from Candida antarctica-B (CAL-B) oil were tested aiming to evaluated its potential in the glioma treatment in vitro (C6). AGs reduced C6 cell viability in a dose dependent manner while were not toxic to normal glia cells. Both FAA1 and FAA2 caused apoptosis cell death and also loss of mitochondrial integrity probably by inhibiting PI3k/AKT pathway. Furthermore, FAAs were capable of reduce the C6 migratory potential. In conclusion FAAs have a promising potential to treat glioma-type brain cancer.
Acesso aberto (Open Access)
Avaliação da influência do tratamento com indometacina no aprendizado e na memória espacial em modelo murino de diabetes tipo 1
(Universidade Federal do Pará, 2017-05-25) SANTOS, Gabriel Cardoso de Queiroz; BASTOS, Gilmara de Nazareth Tavares; http://lattes.cnpq.br/2487879058181806
Diabetes mellitus (DM) is the group of metabolic disorders that has as a common characteristic the disregulation of blood glucose levels, invariably leading to hyperglycemia. This disease has become the most frequent in the adult population, mainly in developing countries, causing several serious consequences such as cardiovascular and renal diseases, factors responsible for a high mortality rate of the individuals affected. In addition that consequences, which are better investigated and described in the literature, other types of complications are observed. Clinical and experimental studies demonstrate that both type 1 and type 2 diabetes mellitus may contribute to the development of cognitive deficits and dementias. However, the mechanisms that lead to such disorders are not yet fully understood. A study using the non-selective non-steroidal anti-inflammatory, indomethacin, has shown that aspects related to impaired neuronal plasticity in diabetes can be reversed, demonstrating that these disorders may be modulated by neuroinflammatory changes. The aim of the present study was to evaluate the influence of chronic treatment with indomethacin on memory and learning in a murine model of type 1 diabetes mellitus (T1DM). Using the open field test, Y-maze test and Morris water maze test we investigated the indomethacin effects on behaviors changes after aloxan inducing T1DM. Indomethacin significantly decrease related behaviors to the anxious state in Open field test. This treatment also reversed space work memory deficits in the Y-maze test, and learning and spatial memory deficits in the Morris Water Maze. Thus, it can be concluded that chronic treatment with indomethacin has beneficial effects on the cognition of mice submitted to type 1 diabetes mellitus.
Acesso aberto (Open Access)
Avaliação da marcha e do equilíbrio em pacientes portadores de síndrome lipodistrófica secundária à terapia antirretroviral
(Universidade Federal do Pará, 2013-09-25) LIMA, Ramon Costa de; CALLEGARI, Bianca; http://lattes.cnpq.br/0881363487176703; SILVA FILHO, Manoel da; http://lattes.cnpq.br/2032152778116209
The Acquired Immune Deficiency Syndrome (AIDS ) is a disease that devastates the world's population decades and hear this diagnosis was like a " death sentence " . With the advent of new drug therapies, characteristic of the acute disease has become a chronic condition . However , the drugs used in antiretroviral therapy (ART ) have adverse reactions , especially when the patient is subjected to long-term use of so-called "cocktail " . One of the side effects of ART is lipodystrophy , which causes the molecular scale adpócitos apoptosis and mitochondrial alterations in the muscle fibers . Thus, the objective of this study was to investigate the effects of muscle Lipodystrophy and changing patterns of gait and balance of patients in this clinical contexto. Were evaluated 38 subjects of both sexes, divided into two groups: HIV positive with lipodystrophy (HIVL) and HIV positive without lipodystrophy (HIV). The balance test was used a force platform (EMGSystem of Brazil), which evaluates the displacement of the pressure Center (Cop) in the anteroposterior directions (AP) and mediolateral (ML) of the individual generating the variables the total linear displacement, total area of displacement and displacement velocity amplitude of the displacement at a time of sixty seconds for each collection. For the gait test we used the 8-channel Electromyograph (EMGSystem of Brazil) to capture the electrical signals of the muscles Rectus Femoral (RF), biceps femoral (BF), gastrocnemius Lateral (GL), anterior tibialis (TA) and Gluteus Médius (GMD) during ambulation and processing of electromyographic signal was made through the mathematical model Root Mean Square (RMS), and normalized by maximum voluntary contraction (MVC). The results of each group were expressed as mean and standard deviation and compared using the Student t test for parametric samples and the Mann-Whitney test for nonparametric samples. Analysis of the results in the two phases of the gait cycle showed significant differences. In the phase of support and swing phase electromyographic signals of GMD and TA muscle were higher in HIVL group for HIV group. As for the balance variables with statistical significance when comparing the groups were the total displacement and displacement area, both higher in HIVL group for HIV group. Thus we conclude that patients with lipodystrophy syndrome showed changing patterns of gait and balance.
Acesso aberto (Open Access)
Avaliação de biomarcadores sorológicos em um estudo de busca ativa de casos novos de hanseníase em área hiperendêmica
(Universidade Federal do Pará, 2016-10-07) GOBBO, Angélica Rita; SALGADO, Claudio Guedes; http://lattes.cnpq.br/2310734509396125
Leprosy is a cronic infection diasease clinically characterized by changes in tactile, thermal and painful sensitivity in skin and peripheral nerves. Due to the absence of laboratory diagnosis of leprosy, new tools that contribute for identification of cases are necessary for enable patient treatment before progression to physical disabilities. In this sense, the present study aimed evaluate serological biomarkers contribution for early diagnosis of leprosy. Was perfomed an active case finding study in Mosqueiro district, Belém – Pará. All individuals were clinically examined by experient leprologists doctors and than 5mL of peripheral blood were colleted for future titration of anti-ND-O-BSA, anti-LID-1 e anti-NDO-LID by ELISA. The action of active finding in Mosqueiro district diagnosed 104 new cases of leprosy between 895 subjects examined (11.6%), indicating a high hidden endemy that agree with the high seroprevalence between schoolchildren. Were observed a significant difference among patients with late or early diagnoses, mainly in multibacillary forms. All biomarkers tested showed promising results in detection of late cases, such as related in literature, however, for early cases those molecules identified correctly only 50% of patients. None of biomarker tested presented sufficient sensitivity to detect all leprosy patients, early or lately diagnosed. Besides, LID-1 molecule had evidenced a lower sensitivity for early cases, their high especificity and accuracy suggest their use as a potential tool for serological screening to identify assintomatic subjects with high risk of illness. Thus, we concludes that besides no biomarker had reveled utility as a serological diagnostic tool, the detection of anti-LID-1 presented a possible aplicability as a screening marker of subjects with increased risk to develop leprosy, contributing indirectly for leprosy diagnosis.
Acesso aberto (Open Access)
Avaliação do efeito antigenotóxico e anticitotóxico do bioproduto método CANOVA®
(Universidade Federal do Pará, 2012-09-28) NASCIMENTO, Henrique Fonseca Sousa do; BAHIA, Marcelo de Oliveira; http://lattes.cnpq.br/3219037174956649
The CANOVA® (CA) method is a Brazilian homeopathic immunomodulator. CA is indicated in clinical conditions where the immune system is impaired. N-Methyl-Nnitrosourea (NMU) is an N-nitroso carcinogenic alkylating agent used as an experimental model in rodents and monkeys. NMU also shows genotoxic/mutagenic effects that can be assessed by classical tests such as detection of DNA damage and chromosomal aberrations. Although several studies have shown promising results in the use of CA, there are no studies reporting possible antigenotoxic effects of this medicine, despite its anticancer potential. Therefore, the present study evaluated the in vitro antigenotoxic and anticytotoxic effects of CA in human lymphocytes exposed to NMU. Samples of human lymphocytes that were subjected to different concentrations of a mixture containing CA and NMU were used in the present study. The viability of cells exposed to NMU was evaluated by MTT assay, CA genotoxicity/antigenotoxicity was evaluated by the comet assay and CA anticytotoxicity was assessed by quantification of apoptosis and necrosis using fluorescent dyes (acridine orange/ethidium bromide). The MTT assay showed that NMU was able to decrease lymphocyte viability significantly. By using the comet assay it was observed that CA significantly reduces DNA damage induced by NMU, which sets a clear antigenotoxic effect of the homeopathic compound. CA also reduced significantly the frequency of NMU-induced apoptosis after 24 hours of treatment. We conclude that CA had an antigenotoxic and anticytotoxic effect in the conditions evaluated in this study, thereby demonstrating a clear cytoprotective potential.
Acesso aberto (Open Access)
Avaliação do efeito citoprotetor do composto homeopático canova® em linhagem celular de rim de macaco verde africano (VERO) exposta ao fármaco dipirona sódica
(Universidade Federal do Pará, 2018-03-01) BONFIM, Laís Teixeira; BAHIA, Marcelo de Oliveira; http://lattes.cnpq.br/3219037174956649
Paracetamol, sodium dipyrone and ibuprofen are among the main medicines exempt from medical prescription available in pharmacies in Brazil. Sodium dipyrone is highlighted in the literature as one of the most commonly used drugs. Despite its wide use, our research group demonstrated that sodium dipyrone exerts genotoxic and cytotoxic effects. Therefore, studies with medicines that may provide protection or that ameliorate the possible damages caused by sodium dipyrone are very important. The homeopathic compound Canova® (CA) seems to be a good candidate for such purpose, since in combination with other drugs it seems to soften the side effects of such drugs. Therefore, the present work aims to evaluate the possible cytoprotective effect of CA on African green monkey kidney cell line (VERO) exposed to the drug sodium dipyrone using the comet, micronucleus, apoptosis and immunocytochemistry assays. Results obtained by the comet test showed that sodium dipyrone induces an increase in DNA damage index of the VERO line. However, when such cells were co-treated with CA at the three concentrations studied, a significant reduction in the ID was observed, indicating a possible antigenotoxic effect of CA. We observed in the apoptosis and necrosis assays that dipyrone induced an increase in the percentage of apoptosis in both 24 hours and 48 hours. However when the drug was associated with CA, a significant reduction in this effect was observed in the three concentrations of CA + dipyrone. Results on immunocytochemistry showed an increase in the expression of caspase 8 and cytochrome C when cells were exposed to dipyrone. On the other hand, co-treatment significantly reduced such effect. Expression of caspase 9 was also observed after dipyrone tratament, however, co-treatment did not reduce such effect. Therefore, in our experimental conditions CA acted as a cytoprotect agent against the damages induced by dipyrone.