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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Acesso aberto (Open Access)
Avaliação pré-clínica da duloxetina em modelo de convulsão: análise comportamental, eletroencefalográfica e influência no estresse oxidativo
(Universidade Federal do Pará, 2014-06-17) COELHO, Danielle Santana; CRESPO LÓPEZ, Maria Elena; http://lattes.cnpq.br/9900144256348265
Epilepsy is a disorder with high prevalence and severity. Although there are several anticonvulsant drugs available in the market, 30 to 40% of the patients are refractory to the treatment. Besides the seriousness of epilepsy per se, this disorder may be accompanied by many comorbidities such as depression, which is the main psychiatric comorbidity of epilepsy. The mechanisms involved in the relationship between epilepsy and depression are not clarified. Given that some anticonvulsant drugs can trigger or enhance depressive symptoms, while some antidepressant drugs can potentiate the severity of seizure, the concomitant treatments of both disorders can be problematic. On the other hand, some studies have shown that antidepressant drugs can be safe and even possess an anticonvulsant activity such as venlafaxine, a serotonin and noradrenaline reuptake inhibitor (SNRI). Considering that duloxetine, another SNRI, has a more potent inhibition of monoaminergic transporters and that there is no study about its influence on seizures, the aim of our study is to verify the potential anticonvulsant action of duloxetine against seizures induced by pentylenetetrazole (PTZ) on mice. With this aim, mice will be pre-treated with duloxetine (10, 20, 40 mg/kg/i.p.), and thirty minutes after, the animals will receive an intraperitoneal injection of PTZ (60 mg/kg, i.p.). In the following twenty minutes the animals are going to be evaluated. The threshold for the first myoclonic jerk, tonic-clonic seizure, the duration of seizures and survival will be quantified. The electroencephalographic analysis (EEG) was used to assess the severity of the seizures (wave’s amplitude increase). After this period the animals will be sacrificed, the cerebral cortex dissected and biochemical analysis (activity of superoxide dismutase (SOD), catalase (CAT), nitrite levels and lipid peroxidation) will be made to investigate the mechanisms by which this drug can influence seizures. The results exhibit the anticonvulsant action of duloxetine. The drug was capable of enhancing the threshold for the first myoclonic and tonic-clonic seizures induced by PTZ. Additionally, the EEG demonstrated that duloxetine at the dose of 20 mg/kg decreased significantly the amplitude of the waves while at the dose of 40 mg/kg it increased the amplitude when compared to all the treatments. Regarding the evaluation of duloxetine’s influence on oxidative stress, all the animals treated solely with PTZ presented a significant increase on lipid peroxidation and a decrease on SOD and CAT activity. Concerning nitrites’ level, there was no difference between the treatments. The dose of 20 mg/kg of duloxetine showed a significant protection against the alterations in oxidative stress induced by PTZ. The anticonvulsant action of duloxetine (20 mg/kg) collaborates with the theory which has been presented in the last few years where it is proposed that the modulation of the serotonergic and noradrenergic neurotransmission may exert an anticonvulsant activity. Moreover, the efficiency of duloxetine in preventing the aggravation of oxidative stress involved in the seizures induced by PTZ corroborates with studies that demonstrate that anticonvulsant substances can influence seizures through its antioxidant activity. Given these points, we conclude that duloxetine is a promising adjuvant for the treatment of patients with the comorbidity epilepsy and depression.
Acesso aberto (Open Access)
Dislipidemias e síndrome metabólica em populações expostas ao mercúrio: estudo observacional de coorte nas regiões do rio Tapajós e Tucuruí
(Universidade Federal do Pará, 2016-09-30) CAMPOS, Núbia Fernanda Santos da Silva; CRESPO LÓPEZ, Maria Elena; http://lattes.cnpq.br/9900144256348265
Cardiovascular diseases have emerged as the leading cause of death in Brazil and in the world, representing a third of the deaths and the main spending on health care. Between 2000-2010, the number of deaths from cardiovascular disease in one hundred thousand inhabitants increased by 28% in the North, with dyslipidemia and metabolic syndrome among the main risk factors. These values become more worrying as it may be underestimated because of consequential underreported the geographical isolation of the region, which is characteristic of northern Brazil. Dyslipidemias correspond to changes in the plasma lipid profile, and represents a criterion for the diagnosis of metabolic syndrome. Metabolic syndrome can be defined as a set of metabolic changes such as hyperglycemia, dyslipidemia, hypertension and obesity. Recently, animal studies and clinical models have shown increased risk of atherosclerotic disease and hypertension with exposure to mercury. In the Tapajós River region, several studies have shown human exposure in riverine populations that consume fish contaminated with methylmercury. Also, recent data from our group show that the riverine communities of Tucuruí have high levels of mercury. The aim of this observational cohort study was to analyze the possible lipid abnormalities and the presence of metabolic syndrome in riverside communities in the Amazon region: Boa Vista do Tapajós, Barreiras, Pimental, Brasilia Legal, Fordlândia and Pedra Branca (Tapajós), Vila Cametá and community Ouro Verde (Tucuruí) with mercury exposure history. For this, the calculations were carried out in body mass index (by weight and height), blood pressure measurements, analysis of glycemic control (fasting blood glucose) and lipid, by plasma levels of triglycerides, total cholesterol, HDL and the calculations LDL, VLDL and HDL cholesterol did not the lipid. After application of the inclusion and exclusion criteria, a total of 337 adults of both sexes (220 of the Tapajos and 117 Tucuruí) were analyzed. High average levels of obesity and high frequency of individuals who had dyslipidemia were detected, especially in Tucuruí, where the frequencies were even higher than in the Tapajos. Also, high percentages of individuals were identified with metabolic syndrome (14% to 35% depending on the definition adopted). The criteria adopted by the NCEP have proved the most sensitive for the identification of metabolic syndrome (MS) in these populations. The main factor that contributes to the detection of the presence of MS was the low HDL level, present in 32% of individuals with MS. In Tapajós, the second and third most common factors were the high levels of triglycerides and glucose, however in Tucuruí was altered blood pressure and high triglycerides levels. In conclusion, our study provides, epidemiological data on the prevalence of dyslipidemia, overweight and obesity, high blood pressure and metabolic syndrome in adults bordering the Amazon. Adding to this, the epidemiological assessment of the lipid profile is an important tool for the promotion of health measures to prevent and reduce cardiovascular risk factors.
Desconhecido
Genotoxicidade humana e fármacos antidepressivos: avaliação da duloxetina em culturas de linfócitos
(Universidade Federal do Pará, 2014-05-29) ARAÚJO, Daniella Bastos de; CRESPO LÓPEZ, Maria Elena; http://lattes.cnpq.br/9900144256348265
Antidepressants are widely used for the symptomatic treatment of depressive disorder. Numerous current research on depression has contributed to the advancement of drug therapy and the emergence of new antidepressant drugs. Current guidelines for genotoxicity testing of new drugs suggests the important utility of assays that detect DNA damage, or tests to evaluate the induction of DNA breakage. However, the small number of data on the genotoxicity of drugs causes the number of drugs that can actually be used safely is reduced. Therefore, it is of utmost importance genotoxicology studies on the evaluation of drugs, especially drugs used for a long period of time such as antidepressants. Duloxetine is a new antidepressant belonging to the class of selective serotonin reuptake inhibitors of serotonin and norepinephrine (SNRIs), used in the symptomatic treatment of depression. Despite the existence of studies showing that some antidepressant drugs are genotoxic, there is to date no study on the possible genotoxicity of duloxetine in human cells. Thus, this study aims to explore the possible genotoxic potential of duloxetine in vitro in primary cultures of human lymphocytes through the techniques of detection of chromosomal aberrations and micronuclei. Primary cultures of blood lymphocytes of healthy volunteers were exposed to different concentrations of duloxetine (10-150 ng/ml) and cyclophosphamide (6 μg/ml) as a positive control. Structural chromosomal aberrations, mitotic index, nuclear division index, index binucleation, number of cells with one, two, three and four micronuclei and the number of cells with nucleoplasmáticas bridges were evaluated. All cultures incubated with indices of duloxetine were significantly lower than those of the control groups, indicating a degree of cytotoxicity of the drug. However, only concentrations of 100 and 150 ng/ml caused a significant increase in the presence of chromosomal aberrations and micronuclei. Whereas these concentrations are close to the upper limit of the therapeutic range of the drug used in humans, our results call already on the need to deepen their understanding of human genotoxicity of duloxetine.
Desconhecido
Malária e medicina popular: efeito da Bertholletia excelsa H.B.K. (Castanha-do-Pará) em camundongos infectados com Plasmodium berghei
(Universidade Federal do Pará, 2013-06-25) GAMA, Layse Martins; CRESPO LÓPEZ, Maria Elena; http://lattes.cnpq.br/9900144256348265
Malaria is a serious problem of public health, especially in Amazon region. However, factors such as drug resistence, difficult access and toxicity of traditional drugs reduce the effectiveness of treatment. Thus, Amazon population uselly uses natural resources, such as Brazil nuts, to improve the clinical symptoms of malaria. However, there is no scientific evidence of the effect of this fruit in malaria. So, this study evaluated the effect of pretreatment with Brazil nuts in BALB/c mice infected with Plasmodium berghei by analysing the following parameters: survival to death of all individuals, parasitemia and weight of the animals (in the 3rd, 7th, 10th, 16th and 18th day post-inoculation of the parasite), and, at the 10th of infection, complete hemogram, liver and spleen weight and analysis of hepatic aspartate aminotransferase (AST), alanine aminotransferase (ALT) and ɣ-glutamyltransferase (GGT). Kolmogorov-Smirnov test was used to evaluate normality, followed by analysis of variance (ANOVA) one-way test or Student t test, followed by Tukeypost hoc test. Monitoring of parasitized animals showed a mean survival of 13.9 days, loss of weight, enlarged organs, and changes of both the hemogram (decrease in hematocrit, hemoglobin, red blood cells and platelets and increased of total eukocytes) as hepatic enzymes (increased AST and ALT and decreased GGT). Interestingly, pretreatment with the fruit of 11 days show a significant protection of animals survival (light increase), levels of parasitemia and total leukocytes (decreased), weight of the animal and weight of the spleen (maintenance for a longer time) and ALT and GGT (increase). Thus, these data supports the use of B. excelsa as a nutritional adjuvant on the treatment against the infection caused by Plasmodium.
Desconhecido
Metilmercúrio e mercúrio inorgânico em peixes comercializados nos mercado municipal de Itaituba (Tapajós) e mercado do Ver-o-peso (Belém)
(Universidade Federal do Pará, 2011-12-12) ARRIFANO, Gabriela de Paula Fonseca; CRESPO LÓPEZ, Maria Elena; http://lattes.cnpq.br/9900144256348265
Mercury is a dangerous metal and an important source of environmental contamination in Brazil and particularly in the Amazon. The main target organ of this metal is the CNS where it causes damage that can lead to classic symptoms: ataxia, paresthesia, dysarthria, and changes in the developing nervous system of children. The mercury contamination in the Amazonian rivers increases the amount found in fish, especially those at the top of the food chain, exposing people to mercury poisoning the rivers, since the fish is a central element in the diet of these populations. Therefore, it is essential periodic monitoring of mercury levels in fish species consumed in the region. Our study proposes to identify the levels of methylmercury and inorganic mercury in fish species consumed by the riverside populations of the Tapajós region and compare them with the levels found in the same species obtained in the region of Belém also perform a comparison with results obtained by Dos Santos et al. (2000) and analyzing the current level and the old. Fish were collected in the municipal market Itaituba, Tapajós, and market the Ver-o-Peso in Belém. Muscle samples of each fish were dried and analyzed by the Universidad de Castilla-La Mancha (Spain) for quantification of methylmercury and inorganic mercury. The results obtained in this study showed that only piscivorous fish from the Tapajós region have levels of methylmercury above the limit recommended by WHO (0.5 μg / g). All in all study groups, levels of inorganic mercury are well below this limit. The species was the most contaminated Brachyplatystoma flavicans (Dourada) and even to exceed five times the WHO limit of tolerance. With our data, we can say that the fish of the Tapajós region are still currently exposed to high concentrations of mercury. The non-fish-eating species had low concentrations of organic mercury, is fit for human consumption. This study supports the importance of continued monitoring of the environments considered exposed and not exposed in the Amazon. Knowledge originated by this monitoring definitely foster the development of prevention strategies and government actions before the problem of mercury contamination in the Amazon. Keywords: inorganic mercury, methylmercury, fish, Tapajós, Belém

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