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).

Navegar

Agora exibindo 1 - 13 de 13

Acesso aberto (Open Access)
Análise de patógenos orais entre indivíduos portadores de câncer gástrico e indivíduos sem câncer
(Universidade Federal do Pará, 2021-06) OLIVEIRA, Gyselle Ribeiro de Carvalho; BURBANO, Rommel Mario Rodriguéz; http://lattes.cnpq.br/4362051219348099; https://orcid.org/0000-0002-4872-234X
The loss of teeth and lack of oral hygiene have been associated with the risk of developing gastric cancer in several populations evidenced in epidemiological studies. In this study, we quantitatively compared the proportion of oral pathogens in individuals with gastric cancer and individuals without cancer in a referral hospital in the city of Belém, Brazil. This study evaluated 192 patients with gastric cancer and 192 patients without cancer. Periodontal clinical examination was performed, and all individuals were submitted to the collection of salivary and dental biofilms. When comparing the median periodontal indexesin the gastric and cancer-free groups, it was statistically significant in the gastric cancer group compared to the probing depth of the periodontal pocket. Levels of bacterial DNA were observed in saliva and dental plaque, with a statistically significant difference between individuals with cancer and without neoplasia in all the bacteria surveyed. Significant relationships between biological agents and gastric cancer have been found in bacterial species that cause high rates of periodontal pathology and caries. The results suggest a different quantitative association in the presence of oral pathogens between individuals without cancer and patients with gastric cancer. As noted, it cannot be said that the bacteria present in the oral cavity increase the risk of gastric cancer or are aggravating factors of the disease. However, it is worth mentioning that, as it is part of the digestive system, the lack of care for the oral cavity can negatively affect the treatment of patients with gastric cancer.
Acesso aberto (Open Access)
Análise transcriptômica das linhagens celulares B103 e C6 expostas à ação do metilmercúrio
(Universidade Federal do Pará, 2023-04) BONFIM, Laís Teixeira; FERREIRA, Wallax Augusto Silva Ferreira; OLIVEIRA, Edivaldo Herculano Correa de; http://lattes.cnpq.br/009400771470765; https://orcid.org/0000-0001-6315-3352
The intensification of anthropogenic activities produces a high rate of environmental pollution, mainly in water bodies, where the contamination by metals has become an object of great interest, due to their inability to support such load. Mercury (Hg) is a naturally occurring metal that can be used in the manufacture of home products such as fluorescent lamps, fungicides, and germicides. The entry of Hg into the food chain occurs through the methylation of Hg2+ ions into MeHg. After methylation, Hg is considered highly toxic to humans, and among the main target organs of this intoxication we can mention the brain, since MeHg easily crosses the blood-brain barrier and can accumulate in different brain areas. It is known that, once in the CNS, MeHg can cause extensive cellular damage, such as DNA damage, oxidative stress, neuroinflammation and cell death in both neurons and glial cells. Thus, the objective of this study was to analyze the transcriptomic alterations of cell lines B103 and C6, derived from neuroblastoma and glioma of Rattus norvegicus, exposed to the action of methylmercury. For this, the expression microarray technique was used to evaluate the global profile of gene expression after 24h of MeHg exposure. Our results demonstrate that MeHg induces significant alterations in gene expression of the two cell lines evaluated. The alterations were more prominent in the C6 cell line, in which a greater amount of differentially expressed genes was observed. Among the genes differentially expressed of the B103 cells we can highlight the genes Cdc42se2 (log2 FC -4.055713), Dcx (log2 FC 3.618981) and 4930449C09Rik (log2 FC 3.5129156) at a concentration of 0.1 μM. As for the exposure of 2.8 μM, the genes with the highest FC were Crem (log2 FC -4.027875), Otoa (log2 FC 3.501512) and Dcx (log2 FC 3.423433). In addition to the abovementioned genes, the genes Trim14, Gm14169, Gm30871, Otoa and Dcx were shared between the two exposed groups. As for the C6 lineage, ten transcripts with FC above 3 (Aldh1l2, Dac1, Rps4l, Zbtb46, 6430573p05Rik, Tcf12, Awat2, Muc3, Dclre1b, Slc38a6) are highlighted. In the 6.3 μM treatment, only three genes were altered more than 3 times (Rps4l, Ankdr44 and 2610318N02Rik). It is also noteworthy that three genes were shared between treatments (Rps4l, Lamb 3 and Gm 41386).
Acesso aberto (Open Access)
Atividade neuroprotetora do treinamento físico moderado contra os danos morfofuncionais cerebelares causados pelo consumo de etanol de forma intensa e episódica (Binge drinking) em ratos
(Universidade Federal do Pará, 2019-09) VIEIRA, Kátia Lamarão; LIMA, Rafael Rodrigues; http://lattes.cnpq.br/3512648574555468; https://orcid.org/0000-0003-1486-4013
Ethanol (EtOH) is a psychotropic drug, central nervous system (CNS) depressant, but widely encouraged and consumed by Brazilian society, as well as in much of the world, reflecting on a public health problem. In recent decades, teenagers have been practicing a very common practice, which is binge drinking. The harmful consumption of EtOH promotes, besides biopsychosocial alteration, the homeostatic imbalance that causes neurodegeneration and loss of function with motor disorders. In contrast, the practice of moderate physical training (MPT) has been recommended for the maintenance of physical and mental health, as well as prevention or minimization of the development of some diseases due to motor activity inducing plastic and dynamic changes in the CNS, in order to favor the neurogenesis, synaptogenesis and angiogenesis, besides contributing to the synaptic modulation. In view of the benefits of MPT, it was investigated the neuroprotective effects on motor, tissue and biochemical parameters in the cerebellum of rats exposed to binge-pattern EtOH from adolescence to adulthood. Forty male Wistar rats with 30 days old were used and divided into four groups, the control being sedentary animals and treated with distilled H2O; the trained, composed of animals exercised and treated with distilled H2O; EtOH, formed by sedentary animals and treated with doses of 3 g/kg/day EtOH, 20% (w/v); and Trained + EtOH, with exercised animals and treated with doses of 3 g/kg/day EtOH, 20% (w/v). The MPT protocol was performed on a rodent treadmill for 5 days for 4 weeks and binge-pattern EtOH doses were administered by intragastric gavage in the same weeks as the MPT. After this period, the animals were submitted to open field and beam walking behavioral tests. Then, they were euthanized for cerebellum collection, evaluating immunohistochemistry from the levels of trolox equivalent antioxidant capacity (TEAC), reduced glutathione (GSH), nitrite and lipid peroxidation (LPO); as well as Purkinje cell morphology (PC), the fraction of anti-synaptophysine (SYP) and anti-myelin basic protein (MBP) immunolabeled area. According to the result, EtOH caused severe oxidative stress and motor damage, but the execution of the MPT performed promoted neuroprotective effects in the rat cerebellum, among them, the modulation of oxidative biochemistry by the restoration of GSH levels. decreased LPO levels and increased TEAC, as well as preventing neuronal loss, synaptic vesicle damage (SYP) and myelin components (MBP). Therefore, MPT can be considered as a significant therapeutic strategy for the acquisition of redox homeostasis, avoiding oxidative biochemistry imbalance, as well as tissue and functional damage in the cerebellum of rats treated by binge pattern EtOH.
Acesso aberto (Open Access)
Avaliação do efeito da fração lipídica extraída de Agaricus brasiliensis antioxidante e imunomoduladora in vitro e em modelo de sepse letal em murino
(Universidade Federal do Pará, 2021-01) LIMA, Kely Campos Navegantes; MONTEIRO, Marta Chagas; http://lattes.cnpq.br/6710783324317390; https://orcid.org/0000-0002-3328-5650
Sepsis is defined as a potentially fatal organ dysfunction caused by a dysregulated host immune response to an infection. During sepsis, dysregulation of the host response occurs with the excessive release of pro-inflammatory mediators, generation of reactive species with depletion of antioxidant defenses and cellular damage. As a result, the patient develops organ dysfunction. In this context, our group proposes the A.brasiliensis Lipid Fraction (FLAb) as a possible therapy for sepsis considering its immunomodulatory and systemic antioxidant activity in a murine sepsis model. Thus, the present study aimed to evaluate the activity of FLAb isolated in vitro and to evaluate the effect of treatment with FLAb alone or associated with the antibiotic ertapenem (F-Erta) on coagulation, antioxidant and immunomodulatory parameters in the lethal sepsis model in murine. For this, FLAb was kindly provided by Dr. Herta Dalla- Santa from UNICENTRO. In the present study, the antioxidant capacity of different concentrations of FLAb (1.25 and 5 μg/mL) was evaluated and in a RAW 264.7-Luc macrophage cell line, cytotoxicity, phagocytic capacity, nitric oxide, NF-κB activity and cytokines TNF-α and IL-6 were evaluated.The survival rates were analyzed 7 days in a model of CLP sepsis in swiss albino mice (Mus musculus), and treated with CLP+Salt (0.9%), CLP+FLAb (0.2mg/Kg), CLP+F-erta (0.2mg) /Kg; 30mg/Kg). For evaluation of on coagulation, antioxidant and immunomodulatory parameters, the mice were treated by 6 and/or 24h after CLP. In vitro, FLAb show antioxidant and anti-inflammatory activity in both concentrations. In vivo, all CLP+Salt animals died within a maximum of 48 hours while the FLAb and F-Erta treated groups survived the 7 days. During this period, clinical parameters of these animals were evaluated, the septic animals treated with saline showed piloerection, with little active level of consciousness and most of the time they were stopped in the cage, some of them had ocular secretion. In addition, animals treated with saline showed significant weight loss, reduced water and feed consumption resulting in death. The FLAb and F-Erta groups were active, with normal appearance, with normal breathing and heart rate, in addition to consuming water and food within normal limits. In the inflammatory site, peritoneal cavity, the treatment with FLAb showed an anti-inflammatory effect, decreased reactive oxygen species (ROS) and increased GSH antioxidant activity and protected from cell damage, maintaining neutrophil recruitment and nitric oxide levels (NO), reducing the bacterial load. Regarding coagulation parameters (platelet count, tp and ttpa), treatment with FLAb and F-Erta eliminated the bacterial load and protected the animals from tissue damage. In the liver, 6 hours after CLP the treatment with FLAb and F-ERTA was observed in the biochemical parameters protective effect, in addition, it presented immunomodulatory, antimicrobial and antioxidant activity preventing liver damage. In the parameters evaluated in the heart, the treatment with FLAb and F-ERTA after CLP protected the animals from cardiac damage through immunomodulatory, antimicrobial and antioxidant activity. In this sense, FLAb alone showed promise as a treatment and/or adjunct in sepsis, in addition to preventing organic dysfunction in septic animals.
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)
A base molecular das adaptações visuais nos genes das opsinas de Anableps anableps e Phreatobius cisternarum através da análise de transcriptoma
(Universidade Federal do Pará, 2019-03-14) MARILUZ, Bertha Ruth Zelada; SCHNEIDER, Patrícia Neiva Coelho; http://lattes.cnpq.br/9584217233879031
Although vertebrate eyes share the same general organization, many species have developed specializations that improve their visual perception of the environment. These specializations are often reflected in a variety of visual adaptations that involve changes in visual sensitivity, which in turn can be modulated by the variation on the photoreceptors number, by altering the visual pigments or by combining both mechanisms. In the case of adaptive changes in the pigments, these may occur due to structural differences in the pattern of expression and the repertoire amount of the opsin genes family. However, there is no much information regarding adaptive changes on visual pigments over different luminosity on aquatic environments. This research aims to evaluate the molecular basis of the visual adaptations in the opsin genes from Anableps anableps and Phreatobius cisternarum, species present in environments with different light conditions, the first one from a surface environment and the second one from an underground habitat, through transcriptome analysis. This investigation comprises two chapters. The first chapter comprises the studies of the Anableps anableps specie. We combined the analysis of RNA-Seq and in situ hybridization of the eye tissue of this specie aiming to understand them visual adaptations to the aerial-aquatic environment. RNA-Seq data from the eye exhibited a repertoire of 20 non-visual opsin genes, which reflects the environmental heterogeneity these species lives. Likewise, comparative analyzes in protein coding sequences of the opsins allowed the identification of six opsins presenting the typical amino acid motifs of C-type and nine of Group 4, conserved among themselves. In situ hybridization studies on the retina showed asymmetric expression of these non-visual opsins at different stages, as well as during the ocular development. The second chapter presents the studies of the Phreatobius cisternarum specie. We combine histological, molecular and RNA-Seq analyzes to understand the visual and sensorial adaptations of P. cisternarum to the phreatic environment. RNA-Seq data from P. cisternarum head revealed a repertoire of eleven opsin genes, three visual opsins and eight non-visual opsins. Two visual opsins, rh1 and lws, presented amino acid substitutions that potentially contributed to the red and blue shift, respectively. Our histological analysis showed the presence of a rudimentary retina, while the RNA-Seq analysis identified the expression of 38 genes related to the lens fiber cells and 51 genes related to the retinal pigmented epithelium (RPE), indicating that the reduced eyes of P. cisternarum retained some lens structures. The extra-retinal expression of opn4m3 is possibly associated with the peripheral clock regulation. Furthermore, the presence of potential opsin pseudogenes would be regulated by a small retina exposed to a low-light environment. The chapters introduce and provide an overview of the investigation on opsins amino acid substitutions, changes on expression patterns and opsin repertoire size (duplication and pseudogenization), and how these could contribute to the shift in spectral sensitivity and finally visual adaptation of A. anableps and P. cisternarum to their peculiar environment. The present study provides fundamental evidence for the understanding of the adaptive molecular basis in the opsin genes to subterranean and aerial-aquatic environments, in the species P. cisternarum and A. anableps.
Acesso aberto (Open Access)
Dinâmica de sucção disfuncional em lactentes com anquiloglossia
(Universidade Federal do Pará, 2023-11) CUNHA, Bruna Mendes Lourenço; SILVA FILHO, Manoel da; http://lattes.cnpq.br/2032152778116209
Introduction: Breastfeeding is widely recommended as an exclusive diet until 6 months of age and continued until two years or more. Its benefits are numerous and proven, including improving the immune system, a nutrient-rich diet and craniofacial development from the sucking movement. However, not all babies are able to breastfeed due to some difficulties, with ankyloglossia. Known as tongue tie, it can restrict tongue movements, making breastfeeding difficult and, in some cases, being responsible for early weaning. Objective: Compare infant suction in babies with and without ankyloglossia using a microprocessor-controlled pressure sensor coupled to a pacifier. Method: Fifty-five infants from 0 to 2 months of age underwent clinical examination for ankyloglossia, after which they were offered a silicone pacifier connected to the pressure acquisition device and suction activity was recorded. Thus, we extracted the frequency of sucks within a burst, the average suck duration, the burst duration, the number of sucks per burst, the maximum amplitude of sucks per burst and the inter-burst interval. Results: The key difference in newborns with ankyloglossia in relation to control was that they perform longer bursts of suction activity. Conclusion: The longer burst durations are likely a compensatory strategy and may underlie the pain reported by mothers during breastfeeding. We therefore propose a method for objectively quantifying some parameters of infant suction capacity and demonstrate its use in assisting the evaluation of ankyloglossia.
Acesso aberto (Open Access)
Estudo sobre o crescimento do tambaqui (Colossoma macropomom) submetido à dieta suplementada com camu camu (Myrciaria dubia) em água corrente e aquecida
(Universidade Federal do Pará, 2018-09) CANTO, Miguel Angelo de Oliveira; SALGADO, Claudio Guedes; http://lattes.cnpq.br/9601463988942971; DINIZ, Domingos Luiz Wanderley Picanço; http://lattes.cnpq.br/9601463988942971
This study investigated the growth of the tambaqui (Colossoma macropomum) (Cm), an caracid teleost in the Amazon region, in the laboratory. Juvenile fish were submitted to the simulation of the natural conditions of feeding, climate and running water, corresponding to the flood and dry periods of the Amazonian hydrological cycle. In the flood, its diet is predominant of fruits and seeds, the environment is mild (28 ± 2°C) and the current is higher (0.2 to 0.3 m/s). In drought, the feed is based on animal protein, there is no current and the average temperature rises (34 ± 2°C). Therefore, the aim of this study was to investigate the effects of Myrciaria dubia (Md) on the growth of Cm in the drought or flood simulations with respect to the mild (28 ° C) or heated (34 ° C), standing or running water (0,2 or 0.3m/s), and diet with higher (45%) or lower (32%) crude protein (CP) content. For this, juveniles of Cm were acclimatized (70 or 126 days) in tanks of (310 or 500 liters) according to the experimental protocol. Protocol I: diet with fractioned daily supply (3x/day) and supplemented with Md; crude protein (45 or 32%); running water (0.2 m/s) or stopped at 28 or 34°C; analysis of muscle contents of IGF1 and total lipids. protocol II: single or fractioned offer (3x / day); standing or running water (0.3 m/s), intercalated, (12 hours) or continuous; quantification of the cavity fat mass. The results are presented on average plus or minus the standard error of the mean and compared by ANOVA plus Bonferrone post-test. Correlation test for weight, length or cavity fat versus running water; in the conditions of single or fractional supply was performed to verify interrelations between the phenomena studied. A potentiation of body mass expansion rather than length occurred by the diet supplemented with Md in standing and heated water. In contrast similar potentiation occurred for running and heated water in the 45% CP diet. In turn, lower growth performance (weight and length) was observed in the group submitted to a 32% CP diet. The running water also potentiated the accumulation of cavitary and muscular fat of total lipids, suggesting that the swimming effort demands accumulation of potential energy possibly related to the preservation of protein anabolism, since the protein content in the muscle tissue was not altered. On the other hand, the single daily supply of food was not enough to maintain the resulting growth performance to sustained swimming (running water). In the fractioned supply, the group submitted to continuous running water showed the best performance, suggesting that sustained swimming in running water may be a determinant factor for the growth of Cm if it is offered a diet with high protein content, considering the warm environment as the most favorable. Finally, the increased IGF-1 content in the muscle confirms the participation of this growth factor as the final pathway of humoral regulation of muscle hypertrophy. Hypertrophy results in increased swimming effort, and, surprisingly, in response to diet supplemented by Md.
Acesso aberto (Open Access)
Expressão gênica durante o desenvolvimento ocular e regulação de assimetria de opsinas na espécie Anableps anableps, peixe de quatro olhos
(Universidade Federal do Pará, 2022-11) SOUSA, Daniele Salgado de; SCHNEIDER, Patrícia Neiva Coelho; http://lattes.cnpq.br/9584217233879031
The ocular development is a complex process orchestrated by several events that include: cell specification, morphogenesis and differentiation. All these developmental and functional processes are extremely conserved among living vertebrate species, however, unique adaptations are sometimes observed, such as in fish of the genus Anableps. Unlike most fishes, which use their eyes to explore a submerged world, in Anableps anableps (Anablepidae: Cyprinodontiformes), the eye is adapted for the simultaneous perception of a world above and below the water line. These exceptional adaptations include: duplicated corneas and pupils, as well as a specialized retina region associated with simultaneous aerial and aquatic vision, and which have asymmetrical gene expression. Recently, by transcriptomic analysis of the developing eyes of A. anableps, 20 non-visual opsin genes were identified to be asymmetrically expressed between pre- and post-duplication stages of corneas and pupils. Thus, here, we analyzed by in situ hybridization the gene expression of a bistable opsin (parapinopsin) and a neuropsin (Opn5) in A. anableps larvae. Our data showed that the pattern of gene expression of these opsins is symmetrical between the dorsal and ventral retina, respectively, with expression in the ONL, INL and GCL layers. We also investigated the expression of three non-visual melanopsin genes (opn4x1, opn4x2, opn4m3), one eleost multiple tissue opsin (tmt1b), and two visual opsins (lws and rh2-1) in the dorsal and ventral retinas of juvenile A. anableps, after changing the photic conditions in which the juvenile fish were. Then, we showed that in the transition from an environment of high turbidity to one of clear water, opsins have their expression patterns changed. Additionally, by immunofluorescence, we revealed the expression of Lamin A/C, proteins expressed as part of eye development in A. anableps as well as in other developing organisms, as well as in adult individuals. Therefore, we believe that the information described here elucidates many aspects of the molecular mechanisms behind the development and adaptive plasticity of A. anableps’ eyes.
Acesso aberto (Open Access)
O extrato aquoso de Coriandrum sativum L. promove neuroproteção contra alterações motoras e danos oxidativos na progênie de ratas expostas ao metilmercúrio
(Universidade Federal do Pará, 2020-01) RODRIGUES, Keuri Eleutério; PRADO, Alejandro Ferraz do; http://lattes.cnpq.br/7016475842644161; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978; https://orcid.org/0000-0003-3647-9124
This study aimed to investigate the efects of Coriandrum sativum aqueous extract (EACS) on the rat progeny of mothers exposed to methylmercury (MeHg). The presence of bioactive compounds and EACS's antioxidant capacity been evaluated, and the spring were assessed for their total mercury levels, motor behavioral parameters and oxidative stress in the cerebellum. The analysis of the bioactive compounds revealed significant amounts of polyphenols, flavonoids, and anthocyanins, as well as a variety of minerals. A DPPH test showed the EACS had important antioxidant activity. The MeHg + EACS group performed significantly better spontaneous locomotor activity, palmar grip strength, balance, and motor coordination in behavioral tests compared the MeHg group, as well as in the parameters of oxidative stress, with similar results to those of the control group. The MeHg + EACS group alsohad significantly reduced mercury levels in comparison to the MeHg group. Based on the behavioral tests, which detected large locomotor, balance, and coordination improvements, as well as a reduction in oxidative stress, we conclude that EACS had positive functional results in the spring of rats exposed to MeHg.
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)
Significado da expressão de p16INK4A e da perda de heterozigosidade do gene PTEN no carcinoma epidermóide bucal relacionado ao papilomavírus humano
(Universidade Federal do Pará, 2023-06) KATO, Valdenira de Jesus Oliveira; ALCÂNTARA, Diego Di Felipe Ávila; http://lattes.cnpq.br/1794240697748468; https://orcid.org/0000-0001-5045-2265; BURBANO, Rommel Mario Rodríguez; http://lattes.cnpq.br/4362051219348099; https://orcid.org/0000-0002-4872-234X
The p16 and PTEN genes are part of the family of tumor suppressor genes commonly associated with the inactivation of a variety of human cancers. The loss of its expression has been studied worldwide in oral squamous cell carcinoma (OSCC). In this study, we evaluated the hypothesis that p16 cooperates with inactive PTEN during OSCC pathogenesis, especially in tumor aggressiveness and proliferation. For that, 119 OSCC samples were used in which the relationship between HPV infection, p16 expression and PTEN mutations were evaluated throug himmunohistochemistry (IHC), western blot, immunofluorescence and sequencing techniques. The results of this study demonstrated that PTEN has high positivity in patients with more advanced tumor size (p < 0.01) and lymph node metastasis (p = 0.02). Statistical analysis showed that p16 expression was strongly associated with the presence of HPV (p<0.0001), but that its aberrant expression is not related to altered PTEN (p=0.52). It was also observed that 60% of the samples in stage IV (advanced stage of the tumor) were statistically associated with the presence of mutation. It is concluded that PTEN and p16 are suppressor genes that control tumor progression. In the current study, PTEN showed great erreactivity in advanced stages of the disease (greater than seven times). p16 was strongly associated with HPV, but did not show a significant association with any clinical-pathological factor analyzed. Both proteins are of great importance in the prognosis of patients. Viral presence has been shown to decrease tumor aggressiveness. Lesions in advanced stages have a shorter survival, in addition, the presence of mutation was more commonly observed in advanced stages of the disease. It was observed that smoking patients witht he absenceof p16 are significantly associated with a survival rate twice as low.

Navegar

Navegando Teses em Neurociências e Biologia Celular (Doutorado) - PPGNBC/ICB por Área de Concentração "BIOLOGIA CELULAR"