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Item Abordagem computacional para a descoberta de novos inibidores de prolil oligopeptidase 80 de Trypanosoma cruzi(Universidade Federal de Goiás, 2022-05-31) Costa, Vinícius Alexandre Fiaia; Andrade, Carolina Horta; http://lattes.cnpq.br/2018317447324228; Neves, Bruno Junior; http://lattes.cnpq.br/7256565904920282; Neves, Bruno Junior; Campos, Helioswilton Sales de; Charneau, Izabela Marques Dourado BastosChagas disease is a serious infectious disease caused by the trypanosomatid parasite Trypanosoma cruzi. Currently, the benznidazole is the only drug available for treating the disease. However, due to the emergence of benznidazole-resistant parasites, low efficacy in the chronic phase and considerable number of adverse effects, the discovery of new drugs more effective, safer and with innovative mechanism of action is imperative. In this context, the general objective of this work was to identify inhibitors of the enzyme prolyl oligopeptidase 80 (POPTc80), a validated target for Trypanosoma cruzi, using computational methods based on the structure of the target (SBDD) and ligand (LBDD). Initially, the three-dimensional structure of POPTc80 was predicted using three different approaches. After structural refinement and validation, the best 3D structure, obtained from the AlphaFold server, was submitted to structural analysis. In this step, three representative conformations of POPTc80 generated on the DynOmics server were selected using Principal Component Analysis (PCA). These structures were then used as structural bases for the construction and validation of molecular docking protocols in the Glide program. Molecular anchoring demonstrated that the conformation 3 results showed the highest rate of enrichment during screening of a set of active compounds and decoys. Then, the docking poses for POPTc80 inhibitors described in the literature were considered queries for generating and validating shape-based models in the vROCS program. As a result, a 3D structure of the POPTc80 was possible, a validated docking protocol was developed and a specific shape-based model for POPTc80 was also developed. At the end of this process, the best molecular docking protocols and the best shape-based model were used as computational filters for the virtual screening of the ChemBridge library, which made it possible to obtain a set of putative hits that will be experimentally validated in the POPTc80 enzyme in collaboration.Item Ação leishmanicida de extratos de plantas no desenvolvimento de promastigotas de Leishmania amazonensis e estudo do perfil metabólico utilizando a técnica de cromatografia líquida de alta eficiência (CLAE).(Universidade Federal de Goiás, 2006-03-31) MENDES, Josireny Mariano; BEZERRA, José Clecildo Barreto; http://lattes.cnpq.br/9491755585617846Two million new cases of Leishmaniose occur annually in the tropical and subtropical areas of the globe, with a estimate of twelve million people currently infected in world and three hundred and fifty million under infection risk. The Leishmania sort, responsible for the disease, understands many diverse and complex species that present resistance to the drugs used in its treatment, beyond the characteristics undesirable. The effectiveness of the control and treatment of a parasitic disease depends on the detailed knowledge of the cycle of life, metabolism and biology in general of the parasite. The World Health Organization, associated with other agencies of research has stimulated the extract inquiry new of native plants as alternative for the treatment and combat of the parasitic disease In this work one standardized techniques of studies biochemists through liquid chromatography high performace (HPLC) evaluating organic acid excretion and consumption of in promastigotes of Leishmania amazonensis and became fullfilled biotests with Magonia pubescens (tingui) and Glycyrrhisa glabra (alcaçuz) in the concentrations of 25 50 and 100 mg.L-1 The acid had been detected following: lactate oxalate citrate -Ketoglutarate succinate fumarate malate and propionate demonstrated activities in the glycolytic pathway cycle of Krebs and respiratory chain Both the tested extracts had presented leishmanicid action with better effect for Glycyrrisa glabra 100 mg.L-1 and Magonia pubescens 25 mg.L-1 The Glycyrrisa glabra had better action in the stationary phase of growth to opposes it of Magonia pubescens that better acted in the logaritmic phase Chemical components of plants can act directly or indirectly in the metabolism of the parasite affecting essential metabolic pathwaysItem Acidentes de trânsito em capitais selecionadas do Brasil: estimativa da magnitude corrigida e fatores associados à gravidade da lesão(Universidade Federal de Goiás, 2017-08-24) Mandacarú, Polyana Maria Pimenta; Morais Neto, Otaliba Libânio de; http://lattes.cnpq.br/4030124246791320; Morais Neto, Otaliba Libânio de; Duarte, Elisabeth Carmen; Mota, Eduardo Luiz Andrade; Ternes, Yves Mauro Fernandes; Itria, AlexanderIntroduction: Middle-and low-income countries currently account for 92% of all road transport fatalities worldwide, with an increasing trend in mortality rates, the opposite of what occurs in high-income countries. Brazil has a high morbidity and mortality burden caused by traffic. However, one of the limitations of the knowledge of the real magnitude of traffic accidents in Brazil is the lack of qualified information about traffic accidents by mode of transportation and the underestimation of the actual number of fatalities and serious injuries. In this way, the qualification of the databases through the relationship of health and traffic records allows improving coverage, coverage and quality of information, as well as enhances the epidemiological analysis of this disease in the population. Objectives: To estimate the magnitude of deaths and severe injuries using a linkage procedure as well as the percentage of correction for health and traffic data sources in the municipalities of Belo Horizonte, Campo Grande, Curitiba, Palmas, Teresina and Goiania, and to characterize the factors Associated with deaths and serious injuries in Goiania. Method: Two cross-sectional studies were conducted, using a database of traffic victims (VIT), the Hospital Inpatient System (SIH), and the Mortality Information System (SIM). The first in Belo Horizonte, Campo Grande, Curitiba, Palmas and Teresina and the second in Goiania. A linkage procedure was performed in both studies through the RECLINK III program, identifying true pairs with calculation of the percentage of correction of the underlying cause of death, secondary diagnosis or classification of the victim in the traffic database. In the second study, for the definition of the associated factors for deaths and severe injuries, the incidence ratios with a 95% confidence interval were estimated. The comparison of the incidences between the categories of each variable using bivariate and multivariable regression model using the Poisson regression, with robust variance. Results: The results showed that there was a considerable correction of the basic cause of death, diagnosis of hospitalization or classification of the severity of the victim's injury in traffic records in the six capitals. For SIM, the percentage of correction of the underlying cause of death was 29.9%, 11.9%, 4.2%, 33.5%, and 43.9% for Belo Horizonte, Campo Grande, Curitiba, Teresina and Goiania, respectively. For SIH, the percentage of correction of the secondary diagnosis of hospitalization was 51.3% for Goiania, 24.4% for Belo Horizonte, 96.9% for Campo Grande, 100.0% for Palmas and 33.2% for Teresina. For VIT, there was a change in the classification of the severity of the victim (not severe to severe), with correction percentage of 100.0% for Belo Horizonte and Teresina, 48.0% for Campo Grande, 52.8% for Goiania and 51.4% For Palmas. In the case of nonfatal to fatal, the correction was 29.5%, 52.3%, 74.3%, 4.4% and 72.9%, respectively, for Belo Horizonte, Campo Grande, Curitiba, Palmas and Teresina. For Goiania, the contribution of the linkage procedure to the database of victims was the identification of 15 deaths (9.6%), not classified as such in the transit data base. In Goiania, 70% of all victims were males and 43.7% of all victims were aged between 18 and 29 years and 63% of all accidents were motorcycle occupants. The main factors associated with death were: age over 40 years (40-49 years: RI 2.75, IC 1.11-6.79, 50-59 years: RI 4.46, IC 1.8- 11.04 and 60 and more: RI 7.69, IC 3.15-18-78) bicycle occupants (RI 2.26 IC 1.19-4.3) and pedestrians (RI 2.12 IC 1.26 -3.58) and the occurrence of the accident between 0-6 hours (RI 2.47 IC 1.36-4.47); For the severely injured were: the age group over 40 years (40-49 years: RI 1.62, IC 1.26-2.08, 50-59 years: RI 1.48, IC 1.23-2, 16 and 60 and more: RI 2.00, IC 1.50-2.66), occupants of Motorcycle (RI 2.38 IC 2.01-2.83), Bicycle (RI 2.35 IC 1.76- And the occurrence of the accident between the periods of 00: 00-17: 59 hours (00:00 to 05:59 RI 1, 38 IC 1.1-1.73.06.06 at 11.59 RI 0.72 IC 0.63-0.83; 12:00 at 17.59 RI 0.84 IC 0.73-0.95). Conclusion: The study contributed to the qualification of the coverage and quality of the information of the health and traffic data banks, as well as identified gaps and limitations in the information system that registers ATT.Item Adesão a terapia antirretroviral, mensurada por diferentes métodos, em pacientes HIV/AIDS atendidos em hospital universitário de Goiânia(Universidade Federal de Goiás, 2011-02-11) Sousa, Clarissa Alencar de; Turchi, Marília Dalva; http://lattes.cnpq.br/3769826743537934; Turchi, Marília Dalva; Albuquerque, Maria de Fátima Pessoa Militão de; Souza, Marta Rovery deIntroduction: Highly active antiretroviral therapy (HAART) changed aids morbidity and mortality profile, decreasing opportunist diseases and deaths. However, adherence is determinant to ensure long-term benefits. This study aims to compare three measures of adherence to HAART and to estimate frequency and related factors of this event. Methods Cross-sectional study conducted among 249 adults, receiving HAART in a public referral center (Hospital das Clínicas/UFG), in Goiás, from 2009 through 2010. Three measures of adherence were investigated 1) Patients who scored > 75 points at the Questionnaire CEAT-VIH (Remor E et al, 2007) were considered adherent. 2) Patients who reported taking more than 95% of the prescribed antiretroviral pills in the past 7 days were considered adherent. 3) Pharmacy refill records measure. Considered adherent those withdrew antiretroviral drugs at the correct time. The prevalence of non adherence and its 95.0% confidence interval (CI) were calculated. Agreement between measures of adherence was assessed using Kappa test. To evaluate the reliability of the measures, undetectable HIV viral load was considered the gold standard. Statistical analyses were performed by using SPSS (13.0) P <.05 was considered significant Results: The majority of participants were men (77.1%), 57.0% had > 8 years of schooling and 61.4% were taking AZT, 3TC and EFV. The prevalence of no adherence, considering missing doses in previous 7 days, was 27.2% (CI95% 17.3 -31.2). According to questionnaire CEAT-VIH, 51.0% (CI95% 49.5 – 52.5) had low/insufficient adherence. According to pharmacy refill records 37.4% (CI95% 35.0 – 39.8) were no adherent. There was a low grade of agreement between the three measures used to evaluate adherence (kappa < 0.40). Adherence was significantly associated with undetectable viral load. Adherence was not associated with gender, schooling or number of pills/day. Being a heavy alcoholic user was associated to poor adherence. Conclusions: Different measures applied to the same patients yielded different levels of adherence, although all three measures were associated with adequate virological response. The estimative of non adherence can be considered high since the majority of patients were taking a low complexity and high tolerability antiretroviral drugs combination.Item Análise bioquímica e equilíbrio ácido-base em Biomphalaria glabrata (Say, 1818), hospedeiro intermediário do Schistosoma mansoni (Sambon, 1907), sob a exposição ao Stryphnodendron polyphyllum (Martius, 1837), planta moluscicida do Cerrado brasileiro.(Universidade Federal de Goiás, 2006-03-31) FERREIRA, Cirlane Silva; BEZERRA, José Clecildo Barreto; http://lattes.cnpq.br/9491755585617846The state of Goiás represents a high risk to schistosomiasis stablishment area The presence of the intermediate host Biomphalaria sp added to high migration levels of people from endemic regions of the country are evidences that favour the installation of this disease life cycle In this state of Goiás there are reports of high parasitary intensity and even cases of paraplegia associated with schistosomiasis. The Stryphnodendron polyphyllum (Martius 1837) known locally as Barbatimão de folha pequena is reported as a molluscicide plant This paper assesses the activity of gross bark extracts from S polyphyllum on the metabolism and on the acid-alkaline balance of B glabrata The mollusks were exposed to the extract at 25 and 50 mg/L concentrations for 24 hours and compared to a control group The concentrations of glucose calcium urea proteins and the activity of the following enzymes dehydrogenases lactate and aminotransferases were estimated using the spectrophotometry method The organic acids citrate propionate α- cetoglutarate succinate acetate malate fumarate pyruvate and lactate were detected and quantified using the liquid chromatography method Of all the organic acids found in the hemolymph, only citrate and propionate presented a significant alteration The acid-alkaline balance was verified by measuring the concentrations found in the pH oxygen carbonic gas carbonate ions and oxygen saturation using Radiomiter equipment The S polyphyllum extract tested proved effective due to celular toxicity on B glabrata(Say 1818) Alterations verified in the biochemical dosages reflect the metabolic disturbances in the hemolymph of the mollusk The Cirlane Silva Ferreira x extract interference caused an increase in the levels of glucose urea calcium aspartate alanine aminotransferases and carbonic gas pressure simultaneously causing a decrease in the levels of lactate dehydrogenase pH oxygen pressure carbonate ions and oxygen saturation This study confirms the bioactivity of the S polyphyllum aqueous extract on B glabrata One of the main contributions of the methodology used is that it enabled observation after direct contact with the extract that proved bioactivity on the metabolism of the mollusk The analysis of the aqueous extract taken from the bark of the barbatimão may be the basis for new and less toxic as well as less costly alternative for the control of schistosomiasis in Brazil, where the savannah is vast and financial resources are often scarce in the health sectorItem Análise da expressão das proteínas META2, LRR17, STI1 e TSA em isolados de Leishmania (Viannia) braziliensis obtidos de pacientes com lesão cutânea ou mucosa(Universidade Federal de Goiás, 2012-02-17) Ávila, Lucilla Ribeiro; Dorta, Miriam Leandro; Oliveira, Milton Adriano Pelli de; http://lattes.cnpq.br/2152513705182408; Castro, Ana Maria de; Afonso, Luis Carlo CroccoIntroduction: Leishmania (Viannia) braziliensis is the most common etiologic agent of cutaneous leishmaniasis in Brazil. About 1 to 10% of patients infected with this species of parasite develop the mucosal leishmaniasis, whose lesions are progressive, destructive and are characterized by a strong specific immune response. The mechanisms for the development of mucosal leishmaniasis are poorly known, but it is possible that proteins associated with virulence of the parasite, such as META2 LRR17 and/or related with the induction of a strong immune response, such as STI and TSA, participate in the pathogenesis disease, causing the appearance of metastases in the mucosa. Objective: To evaluate the expression of proteins META2, LRR17, STI1 and TSA in promastigotes and amastigotes of Leishmania (Viannia) braziliensis derived from cutaneous or mucosal lesions. Methods: It was used three isolates from cutaneous lesions of patients (JCJ8c, and RPL5c SMB7c) and three isolates from mucosal lesions (ASL9m, and JBC8m PPS6m). Amastigotes of the isolates were obtained after inoculation of biopsies in mice knockout in interferon gamma and promastigotes in logarithmic or stationary phase obtained in culture in Grace's medium. The kinetics of growth in culture of isolates was performed by counting daily over ten days in the flow cytometer. The expression of proteins of each isolate was assessed by immunoblotting technique and by flow cytometry, the latter being used only to evaluate the expression of proteins whose expression was significant difference between isolates from cutaneous or mucosal lesions. Results: Promastigotes in stationary phase of the isolates SMB7c and JBC8m were the most expressed the protein META2. The greatest expression of this protein in parasites coincided with more severe lesions, since despite of isolated SMB7c being of cutaneous origin, the patient also presented mucosal lesion, and in the isolated JBC8m the patient presented return of lesions. Proteins LRR17 and STI1 were not expressed in significant amount in both promastigotes and amastigotes of different isolates. TSA protein was expressed at higher levels in promastigotes stationary phase and amastigotes of the xi isolates from patients with mucosal lesions, and this difference was also observed in flow cytometric analysis. Conclusion: The results suggest an association of META2 protein, which is related to the virulence of the parasite, with the generation of more severe lesions in the mucosal, since the highest expression of the protein was isolate from patients with mucocutaneous lesions and patients whose treatment was not effective. TSA, which is associated with antigenicity and virulence of the parasite was also expressed in greater amount in isolates from patients with mucosal lesions. The hypothesis is that, despite TSA protein to induce a protective immune response could be conferring protection in the Leishmania after entering the phagolysosomes by being an antioxidant protein. This protection favored the persistence of parasites and later generation of mucosal lesions.Item Análise da metilação dos genes SOX17, DKK3 e SFRP2, tipos de HPV e associação com a origem e o estadiamento do câncer de colo uterino(Universidade Federal de Goiás, 2017-08-08) Segati, Kelly Deyse; Saddi, Vera Aparecida; http://lattes.cnpq.br/7496804650895441; Santos, Silvia Helena Rabelo dos; http://lattes.cnpq.br/4994826511439492; Santos, Silvia Helena Rabelo dos; Celes, Mara Rúbia Nunes; Paula, Henrique Moura de; Derchain, Sophie Françoise Mauricette; Vettorazzo, Laura Cristina SicheroCervical cancer is caused by persistent high-risk HPV infection. In addition, genetic and epigenetic changes such as the silencing of Wnt signaling pathway inhibitor genes appear to be essential for the development and progression of the disease. This study aimed to analyze the prevalence of HPV infections in cervical cancer and to verify the associations between age, histological type, degree of tumor differentiation and the presence of methylation DKK3, SOX17 and SFRP2. This is a cross-sectional study including cases of cervical cancer, distributed in diagnoses of squamous cell carcinomas and adenocarcinomas. The samples were assayed for 25 HPV genotypes using the INNOLipa® kit, then performed M-PCR to identify the presence of methylation in the promoter region of the genes DKK3, SOX17 and SFRP2. The results of the research showed that the age is significantly lower for women with cervical adenocarcinomas compared to those with a diagnosis of squamous cell carcinoma. Infections with genotypes 18 and 45 were associated with the diagnosis of adenocarcinomas in women younger than 50 years. Methylation of inhibitors of the Wnt signaling pathway and HPV infections 16, 18 and 45 are frequent events during multistage carcinogenesis, however, only a significant association with SFRP2 methylation was observed. The methylation of gene promoter SOX17 was related to lower cervical cancer severity but not to HPV types. Adenocarcinomas were significantlyassociated with HPV infections 16, 18 and 45, and demonstrated a borderline association with DKK3 and SOX17 methylation. In summary, the results of the present study contribute to a better understanding of carcinogenesis of the cervix in the Center-West of Brazil.Item Análise da resposta imune celular de pacientes com tuberculose pulmonar ativa contra os antígenos recombinantes MPT-51, GLcB, ESAT-6, Ag 85A e a proteína do filtrado de cultura (CFP) de mycobacterium tuberculosis(Universidade Federal de Goiás, 2008-02-21) VASCONCELOS JUNIOR, Arioldo Carvalho; KIPNIS, Ana Paula Junqueira; http://lattes.cnpq.br/1252262903952987This work characterized the specific cellular immune response of TCD4 and TCD8 lymphocytes against recombinant Mycobacterium tuberculosis at the Hospital Anuar Auad, Goiania Brazil, and constituted of two experimental groups: 1) 22 active TB patients with positive acid fast aputum, X-ray indicative of tuberculosis, smear culture positive for M. tuberculosis and HIV negative. 2) 15 sex and age matched healthy controls, tuberculin skin test and HIV negative. Venous blood was drawn and processed to obtain PBMC that were cultivated for 96 hours with the specific antigens (1mg/106 cells). TCD8 and TCD4 cells were analyzed by flow citometry for IL-10 and IFN-g production. In general, the percentage of positive TCD4 and TCD8 cells for IFN-g and IL-10 were superior among the TB patients. Additionally, TCD4+IFNg+ (5,63±2,43) and IL-10+ (5,83± 2,19) cells were significantly higher in TB patients than in healthy controls (TCD4+IFNg+ =1,75±0,71 and IL-10+ =1,47±0,90), (p<0,01). Regarding the percentage of TCD8 cells, a higher percentage of IFNg+ (4,33±1,45) and IL-10+ (4,01±1,14) among TB patients than controls (TCD8+IFNg+ = 1,49±0,42 and IL- 10+ 1,62±0,59) was observed (p<0,01). TB treatment did not alter the response to the tested antigens immediately after the treatment initiation. In conclusion, the recombinant antigens MPT-51, ESAT-6, GLcB, Ag85A were recognized by the specific immune response of active TB patients. Key words: Tuberculosis, Mycobacterium tuberculosis, Recombinant antigens, Cellular immune response. to the tested antigens immediately after the treatment initiation. In conclusion, the recombinant antigens MPT-51, ESAT-6, GLcB, Ag85A were recognized by the specific immune response of active TB patients.Item Análise da variação de IgG3 e IgG total específicas para antígenos de Leishmania (Viannia) braziliensis em soro de pacientes com leishmaniose cutânea antes e após o tratamento(Universidade Federal de Goiás, 2015-09-18) Andrade, Douglas Oliveira; Oliveira, Milton Adriano Pelli de; http://lattes.cnpq.br/2152513705182408; Oliveira, Milton Adriano Pelli de; Pereira, Ledice Inácia de Araújo; Lino Júnior, Ruy de SouzaLeishmaniasis are a group of endemic diseases in 98 countries, with an estimated incidence up to 1.6 million cases per year (0.7-1.2 million of cutaneous leishmaniasis and 0.2 to 0.4 million visceral leishmaniasis). The criteria for the cure of american tegumentary leishmaniasis adopted nowadays is the complete healing of the lesion. IgG3 subclass anti-leishmania antibodies decrease faster than the total IgG antibodies in cured patients. This study was aimed to identify differences in the recognition pattern of L. (V.) braziliensis protein by total IgG or IgG3 antibodies obtained from cutaneous leishmaniasis infected patients’ serum before and after treatment. Sera of 15 patients infected with L. braziliensis attended at the Tropical Diseases Hospital Anuar Auadi were tested by ELISA against crude extracts of L. braziliensis. When all patients were analyzed, it was observed that anti-leishmania IgG3 absorbance levels measured by ELISA were similar to the controls levels at 6 month. The absorbance levels of total antibodies in control and infected patients reached similarity only at 12/18 months. After split patients into group A: healing of the lesion before one month and B: healing of the lesion after one month, it was observed that absorbance levels in ELISA for IgG3 in group A was similar to the controls levels at the time of diagnosis. It was also observed, by Western Blotting, that the IgG3 reactivity of IgG3 to 49 kDa protein waspresent mainly for group B patients. The 28 kDa protein showed IgG3 reactivity mainly in group B the healing os lesions and the 14 kDa protein showed IgG3 reactivity in some controls our data suggest that the use of 49 kDa protein in ELISA may be useful for diagnosis and following up of patients and the 14kDa protein may be important in false-positive results.Item Análise das Bases Moleculares da Resistência à Isoniazida e Rifampicina em Cepas Obtidas de Pacientes com Tuberculose no Estado de Goiás(Universidade Federal de Goiás, 2010-03-11) ALVES, Sueli Lemes de ávila; KIPNIS, André; http://lattes.cnpq.br/4434965360286741Multidrug-resistant tuberculosis is a challenge worldwide. Rapid diagnosis by molecular techniques can provide a more aggressive and appropriate initial therapy. This study aimed to analyze the molecular basis of resistance to isoniazid (INH) and rifampin (R) of Mycobacterium tuberculosis strains isolated from cases of human tuberculosis in Goiás and to genetically determine the causes of the observed resistances. Of the 4.607 cultures for mycobacteria processed in the period of September of 2005 and December of 2007, 24 isolates from 16 patients resistant to at least H and/or R were analyzed. We compared the results obtained by phenotypic tests with mutations in key genes responsible for the development of resistance to these drugs, the rpoB gene for isolates resistant to R and katG gene for strains resistant to H. Seventy one percent of the isolates were resistant to H, and the mutations involved with resistance observed in the katG gene were in codon 315 (41%). The most frequent mutations observed in the rpoB gene of the R resistant isolates (71%) were in codons 456 (76.5%) and 451 (17.6%). Our findings are similar to those reported in the literature. We conclude that the percentage of agreement between genotypic and phenotypic tests was 41% for H and 94% for R considering the number of isolates and 40% and 91%, respectively considering the number of patients.Item Análise das interações proteína-proteína da chaperona de cobre ATX1 em Paracoccidioides brasiliensis(Universidade Federal de Goiás, 2022-08-12) Lugo, Danize Eukales Menezes; Silva, Kleber Santiago Freitas e; http://lattes.cnpq.br/3813868830071259; Soares, Celia Maria de Almeida; http://lattes.cnpq.br/8539946335852637; Soares, Celia Maria de Almeida; Pereira, Maristela; Bailão, Alexandre MeloParacoccidioidomycosis is the most prevalent systemic mycosis in the Americas, mainly in Brazil, Colombia, Venezuela and Argentina. The disease is caused by fungi of the genus Paracoccidiodes that exhibit thermodimorphism. The fungus is present in the soil in the mycelial form at 28°C and in the yeast form in the host at 37°C. The ability to differentiate is considered a virulence factor of this pathogen. Copper (Cu) is an essential component of enzymes that carry out electron transfer reactions. Homeostasis of this metal was first described in Saccharomyces cerevisiae and homologous genes were identified in several organisms. Among these, the ATX1 gene, related to a copper metallochaperone, stands out, which transports Cu1+ from Ctr1 (transmembrane transporter) to Ccc2 (P-type ATPase) in a trans-Golgi vesicle for eventual insertion into Fet3. The latter is a highaffinity Cu-dependent iron absorption protein. Atx1 was identified in S. cerevisiae as a small 8 kDa Cu chaperone, being classified as an antioxidant molecule. Little is known about Cu homeostasis metabolism and the specific function of the ATX1 gene in Paracoccidioides brasiliensis. Thus, the identification of Atx1 interaction networks in P. brasiliensis can elucidate details of Cu metabolism in this organism. The main objective of this research was to characterize, through molecular anchoring, how ATX1 interacts with P. brasiliensis proteins, providing an understanding of the biology of the fungus and aiming to identify possible therapeutic targets as a future perspective. A group of proteins that interact with Atx1 was identified and validated through pull-down assays. These proteins are part of the maintenance of homeostasis, interacting with other proteins of copper metabolism, electron transport and detoxification proteins. These interactions indicate the importance of Atx1 for maintaining copper homeostasis in the fungus, being a potential target for alternative drugs, which may collaborate to expand therapeutic options.Item Análise de resistência a antimicrobianos de cepas de Mycobacterium tuberculosis isoladas no Estado de Goiás(Universidade Federal de Goiás, 2010-12-07) SANTOS, Lorena Cristina; KIPNIS, Ana Paula Junqueira; http://lattes.cnpq.br/1252262903952987; KIPNIS, André; http://lattes.cnpq.br/4434965360286741Tuberculosis (TB) is a serious global public health. In Brazil for the confirmed TB cases is recommended a multi-drug therapy regimen which combines different drugs during at least 6 month. However, because of treatment inconsistency, the emergency and spread of drug resistant M. tuberculosis become a serious threat. Actually, strains resistant to at least one drug used in the TB treatment have been one of the main factor that avoid the effective TB control. According to WHO M. tuberculosis strains that are resistant to at least INH and RMP, the key drugs used in the TB treatment, are considered multidrug resistant (MDRTB). The main mutations responsible for INH and RMP resistance occur at some specific regions in the katG, inhA and rpoB genes. We analyzed by phenotypic and genotypic methods the susceptibility profile of M. tuberculosis isolated from 132 patients treated at a reference hospital in Goiânia-Goiás, between January of 2006 and July of 2007 and then performed the resistant strains genotypic identifications by RFLP-IS6110. Additionally, clinical and epidemiological informations from the patients was collected. A high frequency of drug resistance was observed in previously untreated patients (13.6% to at least one antibiotic and 6.1% MDR-TB), and a high DNA polymorphism was observed among these strains. Our results suggest that the prevalence of resistant TB in Goiás is underestimated and that resistance in new TB cases was not associated with an outbreak in this region.Item Análise do perfil de resistência do vírus da imunodeficiência humana tipo 1 (HIV-1) aos inibidores da transcriptase reversa não análogos de nucleosídeos (ITRNN) em Goiás(Universidade Federal de Goiás, 2010-07-20) Pacheco, Priscila Ribeiro Guimarães; Turchi, Marilia Dalva; http://lattes.cnpq.br/3769826743537934; Turchi, Marilia Dalva; Pereira, Gisner Alves de Souza; Araújo Filho, João Alves deObjectives: To describe and analyze HIV-1 resistance mutational profiles associated with non- nucleoside reverse transcriptase inhibitors (NNRTIs) from patients experiencing antiretroviral therapy failure; at the main reference public Center in Goiás State. Methods: Samples from 474 patients were collected and processed according to the National Genotyping Network (RENAGENO), between 2006 and e 2009. Patient’s files (genotype exams) and medical records were used as data source. Number of TCD4 cells, HIV-1 viral load quantification, viral subtype and mutation profile assessment (TRUGENE HIV-1 Genotyping Test e ViroSeq System) were done according to the routine adopted by Central State Laboratory (LACEN). Resistance mutation profiles were identified using the Brazilian Algorithm and the Stanford Database Program. Cross resistance between NNRTIs: nevirapine, efavirenz and etravirine were analyzed. Descriptive and exploratory analyses were performed for socio-demographics variables and laboratory results (SPSS 15.0). Results: Samples from 126 adult patients were resistant to nevirapine (NVP) and efavirenz (EVF) Subtyping analysis showed a predominance of subtype B (86.1%), followed by BF1 recombinant (7.8%). Half of the patients received three or more antiretroviral therapy regimes. The most frequent mutations were 103N (72.2%) and 225H (22.2%). Mutations related to decreased etravirine (ETV) activity were detected in 8 codons: 98, 100, 101, 181, 188, 190 e 230 Intermediate ETV resistance were present in 27.0% and 15.1% of the samples, according to the Brazilian protocol and to Stanford Db Program, respectively. High-degree of ETV resistance were present in 10 samples (7.9%; IC95% 3.9-14.1), according to the Brazilian protocol Using the Stanford dB Program, 3 out of 126 patients (2.4%; IC95% 3.9-14.1) had high-degree of resistance. Clinical characteristics, number of T CD4 cells and viral load were not predictors to ETV resistance. Conclusions: The presence of at least one mutation potentially associated with decreased virological response to ETV was frequent, in a population highly exposed to NNRTIs. Otherwise high-degree of cross resistance to ETV was not common, suggesting that this drug could be helpful for patients failing to first generation NNRTIs.Item Análise dos resultados sorológico, anatomopatológico e parasitológico de material abortivo para infecções com risco de transmissão vertical com ênfase na toxoplasmose(Universidade Federal de Goiás, 2009-11-05) BARBARESCO, Aline Almeida; CASTRO, Ana Maria de; http://lattes.cnpq.br/9232309971000621The infection caused by Toxoplasma gondii, Trypanosoma cruzi, Rubella virus, Cytomegalovirus (CMV) and Treponema pallidum, can reach the fetus via the placenta or transamniótica may cause different damage. The severity of the infection or even abortion, depend on the virulence of the strain of microorganism, the immune response of the mother and the period. The aim of this study was to analyze the results of serological, pathological and parasitological material for abortive infections with risk of vertical transmission, with emphasis on toxoplasmosis. They were invited to participate in the study, women who miscarried and complete or incomplete, attended at two public hospitals in Goiânia, Goiás, between the period June 2008 to June 2009. Were interviewed through a questionnaire and collected blood samples and abortive material. There were immunologic tests for toxoplasmosis, Chagas disease, rubella, cytomegalovirus and syphilis and pathology in cytogenetic. 55% of women were aged 20 to 30 years of age. The majority (68%) had gestational ages ranging from 7-14th weeks. 54.3% of women had completed high school or incomplete. Regarding the number of abortions, most women (69%) had only one abortion and minority (2.9%) were already in the fourth or fifth abortion. For the analysis of serology, infection with the risk of vertical transmission was more frequent with the CMV 97.1% positivity and then the rubella 95.2%. Toxoplasmosis has a percentage of 54.3%, Chagas disease by 1.9% and syphilis by 0.95%. The analysis of the biopsy showed that 63.1% showed inflammation and 34% absence of inflammation. Analysis of serological, pathological and parasitological of 105 women, 57 were seropositive for T. gondii. It was observed that 77.1% showed inflammation, detected in pathological examination. None has tested positive for Polymerase Chain Reaction (PCR) and inoculation in mice. This study demonstrated the high frequency of seropositive for CMV and rubella then toxoplasmosis, Chagas disease and syphilis in our country. The elucidation of the cause of miscarriage is still not routine in our country. These data showed that the prevalence of disease with risk of congenital transmission in patients with spontaneous abortion is important, more research is needed to elucidate the etiology of abortion. Women's health should receive more attention from our managers because primary care is the best and most efficient path to be followed in order to quality of life for mothers and their future children.Item ANÁLISE ESPACIAL DA INFECÇÃO PELO VÍRUS DO DENGUE NO MUNICÍPIO DE GOIÂNIA.(Universidade Federal de Goiás, 2008-06-02) MACIEL, Ivan José; MARTELLI, Celina Maria Turchi; http://lattes.cnpq.br/5867052489026059Dengue is nowadays considered a growing public health problem worldwide. Several outbreaks of dengue have occurred in Brazil in the last two decades, and the country is now considered an endemic area where risk areas for sylvatic yellow fever also coexist. The current manuscript reviews the main epidemiological features of dengue in the world focusing in the peculiarities of the infection/disease progression in Brazil and, specifically, in Central-West Brazil. Some issues related to the challenge of control in the Central-West region and the opportunities for research are also discussed. In Brazil, the re-introduction of the vector (Aedes aegypti) dates 1976-77. The city of Rio de Janeiro (Southeast Brazil) was considered the starting point of viral dispersion to coastal and inland areas, since the first epidemic (DENV-1) in 1986. Brazil reports approximately 70% of the dengue cases in the Americas with the co-circulation of 3 dengue subtypes (DENV-1; DENV-2 and DENV-3). The disease affects mainly the adult population and the surveillance system has detected an increasing trend to hospitalization, disease severity and incidence in children and adolescents. Approximately 500,000 of dengue cases and 158 deaths were reported in 2007 compared to approximately 300,000 and 77 deaths in the previous year in Brazil. The first epidemic in Goiás State (Central-West Brazil) was reported in 1994. Nowadays the three serotypes co-circulate with high incidence rates and a large outbreak was reported in the city of Campo Grande (Mato Grosso do Sul State) (45,843 registered cases). The recent increase in cases related to sylvatic yellow fever, mainly in Goiás State, represents a public health warning related to vector surveillance and control.Item Análise molecular e de qualidade de vida dos pacientes e familiares com xeroderma pigmentosum, residentes em Goiás, Brasil(Universidade Federal de Goiás, 2016-03-07) Souto, Rafael; Siqueira Júnior, João Bosco; http://lattes.cnpq.br/3644529827602550; Menck, Carlos Frederico Martins; https://orcid.org/0000-0003-1941-0694; Menck, Carlos Frederico Martins; Lacerda, Elisângela de Paula Silveira; Vêncio, Eneida Franco; Teles, Sheila Araújo; Brasil, Virginia ViscondeXeroderma pigmentosum (XP) variant is an autosomal recessive disease that involves changes in POLH. The study aimed to characterize the distribution of alleles mutated by Real Time PCR (RT-qPCR) in patients and families with clinical suspicion of XP, residents in Araras/Faina, State of Goiás. Additionally, we also, planned to evaluate the quality of life (QoL) by WHOQOL-Bref. In this community, the skin cancer incidence, due to this syndrome, is caused by mutation in the POLH gene, which encodes for DNA, polymerase eta, and two distinct mutations were detected, at the intron 6 e exon 8. Morover, at Trindade a different mutation was found in the same gene (intron 10). Molecular analysis by Real Time PCR (RT-qPCR) o 125 individuals at-tempted to identify the mutated alleles in POLH, which can result in disease and impact on quality of life. Of these, 29 clinically diagnosed as affected by XP syndrome, and 18 in the community of Araras/Faina and 11 are from other Goiás State locations. In Araras/Faina, of the 114 individuals analyzed, 12 were homozygous for the mutanted allele at the beginning of intron 6 (XPV 6/6), one homozygous for the mutanted allele at exon 8 (XPV8/8) and 5 are compound heterozygous for compounds two alleles (XPV 6/8). In addition, 36 patients were identified as carrying (as heterozygous) the mutation at intron 6 (XPV 6/wild-tipe) 12 carriers for muta-tion at exon 8 (8 XPV/wild-type) and 48 participants were wild type for the two alleles (XPV wild type/wild). In the study of 11 clinically affected patients and residents in other regions of the state of Goiás, 2 were positive for XPV with mutations in intron 10 (XPV 10/10) and 9 were negative for the three alleles identified in XPV. The Quality of Life evaluation gave relatively high scores when compared to the work of other groups that studied the Tourette syndrome, Wilson's disease and Thalassemia Major. In comparison using the Student t test between QoL scores of patients by XPV and not sick, it was obtained a p ≤ 0.05 for all domains of the WHOQOL-Bref, demonstrating that the XPV impacts the quality of life of those affected. However, even in a more stratified analysis , the comparison between QoL scores and genotypes for XPV, obtained a p ≤ 0.05 for the Physical and Environmental domains. Thus, we believe that molecular tests come uncovering cases of XP that were underreported showing the actual frequency of the syndrome in the state of Goiás, in addition, the measure of the perceived quality of life is showing the impact that these mutations promote affected in the XPV.Item Análise Morfométrica de Staphylococcus aureus Meticilina Resistentes Cultivados em Diferentes Concentrações de Cloreto de Sódio e Oxacilina(Universidade Federal de Goiás, 2010-04-15) OLIVEIRA, Ana Cláudia Alves de; LINO JÚNIOR, Ruy de Souza; http://lattes.cnpq.br/0372118837748010Methicillin-resistant Staphylococcus aureus (MRSA) has been one of the most prevalent microorganisms that cause hospitals infections worldwide. Several studies show that this microorganism is often found colonizing health professionals. MRSA can cause skin infections from the severe pneumonia, with high resistance to different antimicrobial agents. This study aimed to evaluate morphometric changes in MRSA isolated from the saliva of health professionals, through the use of different concentrations of oxacillin and sodium chloride. The identification of morphological changes was assessed by growing the isolates in the following concentrations of Sodium Chloride and oxacillin: 2μg, 4μg and 6μg and 2%, 4%, 6% and 7.5% and using the means of computerized morphometry. This technique was tested by microscopic computed by employing the software Image J 1.38 (HIH USA). Statistical analysis was performed using the Sigma Stat, version 2.03, and the differences between the groups were compared using the nonparametric Kruskal-Wallis (p <0.05). The 20 MRSA analyzed showed no alterations. The present study showed that Sodium Chloride and oxacilin at concentrations did not alter the development and morphology of MRSA.Item Análise proteômica de células a-549 infectadas por adenovírus espécie f sorotipo 40 (HAdV-40)(Universidade Federal de Goiás, 2015-08-06) Guissoni, Ana Carla Peixoto; Cardoso, Divina das Dores de Paula; http://lattes.cnpq.br/9770835116155857; Cardoso, Divina das Dores de Paula; Leite , José Paulo Gagliardi; Barardi , Célia Regina Monte; Fiaccadori , Fabíola Souza; Souza , Menira Borges de Lima Dias eHuman adenovirus (HAdVs) are causative agents of different clinical syndromes such as gastroenteritis, respiratory diseases, eye diseases and cystitis. Adenovirus infection can modify the cellular homeostasis through the interaction with the host cell by inducing proteins of several metabolic pathways. The resulting knowledge of this virus-cell interaction may aid the elucidation of the pathogenic mechanisms caused by adenovirus and the host response against viral infection. To study this interaction, a methodology that has been widely used is proteomics, a tool used in this study, which aimed to identify induced proteins due to viral infection. In this context, we used cells A-549 infected with human adenovirus of type F, serotype 40 (HAdV-40). Infected cells and non-infected cells were used for the osmotic lysis, which were quantified by the Bradford method and then digested with trypsin. Peptides were separated on the LC system in two dimensions. The ionization of the peptides was performed by nano-eletronspray source and through analysis of ToF-MSE system aiming the protein identification. A sum of 336 proteins were identified, 206 of them induced and 130 suppressed by the infection with HAdV-40. The main pathways affected by viral infection were: energy, cellular organization, stress response and apoptosis. It was observed alteration of cell metabolism with increase of the glycolytic pathway, β-oxidation and respiratory chain. Also, the results suggest cytoskeleton reorganization and apoptosis induction. The data can to contribute knowledge about adenovirus pathogenesis considering the proteins related to distinct metabolic pathways induced by viral infection.Item Análise proteômica de membrans de Paracoccidioides sp. durante privação de zinco(Universidade Federal de Goiás, 2014-08-04) Silva, Marielle Garcia; Soares, Célia Maria de Almeida; http://lattes.cnpq.br/8539946335852637; Soares, Célia Maria de Almeida; Casaletti, Luciana; Lima, Patrícia de SousaParacoccidioides spp. are pathogenic fungi that causes paracoccidioidomycosis, an important systemic mycosis in Latin American countries. The success of infection depends on the pathogen ability to obtain essential micronutrients (metals) from the host. This process of nutrient uptake occurs through membrane associated transporters. The membranes are constituted of a lipid bilayer with associated proteins and are involved in different processes during the establishment of infection, such as transport of nutrients and homeostatic regulation. As zinc is a metal that plays an important role in the regulation of host-pathogen interaction and changes in this micronutrient homeostasis are implicated in the pathogenesis of infectious diseases, the aim of this study was to identify the membrane proteins expressed under conditions of zinc deprivation. NanoUPLC-MSE technique was employed in order to identify membrane proteins of yeast cells (Pb01) grown in chemically defined media in the presence and absence of zinc. Transmission electron microscopy was performed to confirm the sample enrichment with membranes. Subsequently, the samples were digested and analyzed by NanoUPLC-MSE. In silico analysis was performed to determine the location of 460 proteins identified in extracts of Pb01 grown in + Zn (control) and TPEN (treated) medium. Among the identified proteins, 141 were classified as belonging to membranes and of those, 120 proteins were repressed and 21 were induced during zinc deprivation. Among the 141 membrane proteins, 81 showed transmembrane domains and 9 were classified as membranes proteins with post-transcriptional modification. A total of 15 membrane proteins showed signal peptide. Analysis of the function of membrane proteins, allowed the description that phospholipid metabolism and cell integrity maintenance pathways were affected by zinc deprivation.Item Análise proteômica de paracoccidioides sp. em condições de estresse osmótico(Universidade Federal de Goiás, 2014-11-28) Rodrigues, Leandro Nascimento da Silva; Soares, Célia Maria de Almeida; http://lattes.cnpq.br/8539946335852637; Soares, Célia Maria de Almeida; Zancopé-Oliveira, Rosely Maria; Casaletti, Luciana; Bailão, Alexandre Melo; Amaral, André CorrêaThe dimorphic fungus Paracoccidioides is the etiological agent of paracoccidioidomycosis, a systemic mycosis with high relevance for the public health in Brazil and other Latin American countries such as Colombia and Venezuela. Generally, microorganisms require responses to stress conditions to survive in response to environmental changes and pathogenic organisms, particularly, require an effective response even higher to react against host defences. Osmotic stress has been used as a model to study signal transduction and seems to cause many cellular adaptations, which include signal transduction pathways modification, protein expression alteration and cellular volume and size regulation. In this work we have evaluated the proteomic profile of yeast cells of Paracoccidioides sp. (Pb01) obtained in osmotic stress condition. Data describe an osmoadaptative response of this fungus when subjected to this treatment. Proteins involved in the synthesis of the cell wall components were modulated, evidencing a remodelling of the cell wall. In addition, it was also observed alterations on the energy metabolism, given that proteins of the pentose phosphate pathway were abundant while proteins of the glycolysis were less abundant under osmotic stress condition. In addition changes in amino acid metabolism were also observed; more clearly the degradation of amino acids such as leucine, isoleucine and valine was induced during osmotic stress. Hereupon, our study suggests that Paracoccidioides sp. (Pb01) present a vast osmoadaptative repertoire; comprising different proteins which act complementarily and that this response could be able to minimize the effects caused by osmotic stress.