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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 Bastos
Chagas 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.
Ação da curcumina e morina em leveduras do Complexo Cryptococcus neoformans
(Universidade Federal de Goiás, 2017-05-12) Freitas, Vivianny Aparecida Queiroz; Fernandes, Orionalda de Fátima Lisboa; http://lattes.cnpq.br/9826992750728262; Fernandes, Orionalda de Fátima Lisboa; Souza, Lucia Kioko Hasimoto e; Melhem, Márcia de Souza Carvalho
Cryptococcosis is a fungal disease caused by yeasts belonging to the complex Cryptococus neoformans. The antifungal arsenal available for the treatment of this disease is still restricted and is related to the high toxicity and side effects of some drugs, causing great harm to the patients. In this context, it is necessary to discover new bioactives to quell the infections and reduce the adverse effects. The plants have rich source of secondary bioactive metabolites such as tannins, terpenoids, saponins, alkaloids, flavonoids and other compounds, registered with expressive antimicrobial properties. Therefore, the research of natural compounds and derivatives of natural products has been relevant in recent years, due to their relevance in the discovery of new drugs, in addition to which the association of drugs or compounds with different mechanisms of action has been used as an alternative in conventional therapy. We evaluated the mechanisms of action and antifungal effect of natural compounds, curcumin and morin, on Cryptococcus neoformans and Cryptococcus gattii isolates. The antifungal activity was determined across the minimum inhibitory concentration (MIC) and minimum fungicide (MFC). Polyphenols showed MICs ranging from 2 to 256 μg/mL. The compounds showed a synergistic interaction in 30% (6/20) and 15% (3/20) of the isolates when dealing with morin and curcumin, respectively, associated with fluconazole. In the interaction with amphotericin B morin presented synergism in 70% (14/20) of the isolates. Both compounds did not exhibit antagonism in any of the combinations. Changes in fungal cell morphology were observed, and in contact with red blood cells, presented low toxicity. The mechanisms of action revealed that both polyphenols act on the membrane of the fungal cell, inhibiting the synthesis of ergosterol and causing damage to it. These results demonstrate the potential of the compounds as natural bioactives, with great impact on the discovery of new drugs and their efficacy to be used in the treatment of fungal infections.
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/9491755585617846
Two 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 pathways
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, Alexander
Introduction: 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.
Acompanhamento de egressos do Mestrado Profissional em Saúde Coletiva: avaliação de uma plataforma on-line
(Universidade Federal de Goiás, 2020-12-18) Silva, Kelly de Oliveira Galvão da; Oliveira, Ellen Synthia Fernandes de; http://lattes.cnpq.br/3128365764211694; Oliveira, Ellen Synthia Fernandes de; Cardoso, Alessandra Marques; Teixeira, Ricardo Antônio Gonçalves
Although collective health, in offering the professional master's degree, seeks to train critical scientists capable of evidencing specific facts by understanding localized situations, seeking solutions and proposing improvements to their work environment, it is evident that the combination of research effectiveness and applicability in public health services, still faces invisibilities on the part of Brazilian evaluation bodies. One of the ways to identify this double objective of the Professional Master in Public Health (MPSC) is to bring the Higher Education Institutions (HEIs) closer to their graduates. In this sense obtaining information on the training received will serve as a subsidy for the improvement of graduate programs in the HEIs. Therefore, the objective of our study was to evaluate the use of an online platform called PortalEgressos by graduates of an MPSC. The research was carried out in Goiânia-GO, from October 2019 to December 2020, and 92 students from the classes of 2013, 2014, 2016 and 2017 were invited to participate. It was a retrospective, descriptive cross-sectional study, exploratory, of the type mixed research with qualitative approach and description of quantitative data. For data collection, the program's registration forms and the information entered by the graduates in the PortalEgressos platform were used from February to June 2020, obeying ethical aspects. The data analysis was carried out through statistical tests and content analysis, according to Bardin, 2011. Through the registration form, the profile of the 92 graduates was drawn, a heterogeneous population, with a varied age range, (22–59 years old), with a majority female representation, most of them are linked to the public health service and the research line with the greatest quantitative of interest was “Management processes in Health services”. In PortalEgressos, in the “about me” tab, it was observed, from the analysis of the perception of the 26 respondents, that the MPSC contributed to their work activities in the health service, improved their critical perceptions and based on theoretical concepts that help in decision making. In the “Interview” tab, 18 participants evaluated performance and expectations regarding the course that said, Wilcoxon test showed the existence of a significant difference between the pairs in questions 3, 4, 7 and 21, in order to elucidate, thus, that there are still gaps to be investigated and improved in the course. Thus, through a virtual tool, aspects could be extracted, with proof of its usefulness in following the graduate, being the instrument of data collection and its analysis as a technical product, that contains the proposal for improvements to the process of evaluation and monitoring of the course.
Adenovírus em amostras fecais e do trato respiratório de crianças atendidas em um hospital de Goiânia, Goiás
(Universidade Federal de Goiás, 2016-12-05) Paz , Thainara Calixto da; Souza , Menira Borges de Lima Dias e; http://lattes.cnpq.br/0054562567103606; Souza , Menira Borges de Lima Dias e; Fiaccadori , Fabíola Souza; Freitas , Érika Regina Leal de
Human adenoviruses (HAdVs) may cause several clinical syndromes, and are a major cause of respiratory and acute gastroenteritis (AGE), especially among children. However, data on viral load, in more than one type clinical sample obtained from the same child, are still scarce. The aims of the present study were to evaluate the frequency of the HAdV, to determine the load viral in clinical samples, and to proceed molecular characterization of positive samples from children up to five years of age in association with symptomatology. For this, 200 children attended at Hospital Materno Infantil in Goiânia, Goiás; between March 2014 ad July 2015. One fecal and one nasopharyngeal swab sample was obtained from each child. The clinical samples (fecal and nasopharyngeal swabs) were submitted the DNA extraction by a commercial kit (Qiagen-Hilden, Alemanha), and screened by RT-qPCR (TaqMan) assay, with specific primers and probe targeting the hexon region of HAdV genome. The global frequency of HAdVs was 21% (42/200). Positivity in swabs was 9.5% (19/200), and in fecal samples 16% (32/200). Among the symptomatic children (n=129), 21% were positive in fecal samples (22/105) and 9.2% (10/108) in swab samples. Futhermore, 4.5% (9/200) were positive in both clinical samples. High viral loads were observed in both fecal and nasopharyngeal swab samples from symptomatic and asymptomatic children, and major positivity was found in symptomatic children with high load viral. High viral loads were observed in samples from symptomatic and asymptomatic children. Major positivity and load viral was found betwenn symptomatic children. HAdV types 3 of species B and 41 of HadV F species were detected. We hope that the data obtained can help in a better understanding of the pathogenesis of HAdV in children.
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 de
Introduction: 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.
Análise bioquímica da niclosamida no metabolismo de cisticercos de Taenia crassiceps
(Universidade Federal de Goiás, 2015-03-09) Costa, Marco Vítor Silva de Melo; Costa, Tatiane Luiza da; http://lattes.cnpq.br/8219041935358486; Vinaud, Marina Clare; http://lattes.cnpq.br/1921551651088660; Vinaud, Marina Clare; Silva, Luciana Damacena; Bezerra, José Clecildo Barreto
Experimental studies with Taenia crassiceps have been used to demonstrate its metabolic alterations in biochemical pathways (energetic and respiratory) in response to the presence of drugs. The use of T. crassiceps as an experimental model offers conditions to reproduce the neurocysticercosis infection one of the most severe form of human cysticercosis. This study aimed the analysis of the in vitro influence of niclosamide, an antihelminthic drug, on the metabolism of carbohydrates and fatty acids of T. crassiceps cysticerci (ORF strain). 20 larval stage cysticerci were cultured into 5mL of RPMI (Gibco) supplemented culture media, in 6 well culture plates, exposed or not to niclosamide (1, 2, and 3 uM). The control groups were performed with cysticerci not exposed to the drug, exposed to ethanol in the concentration used to dissolve the drug. The cysticerci were cultured at 37ºC for 24 hours. After this period the cysticerci were removed from the culture medium and both were frozen with liquid nitrogen. Afterward, the samples were processed for the HPLC analysis. Accordingly to the mode of action of this drug, which is to interfere in the electrons chain transport, the succinate concentrations were altered in the secretion/excretion of this parasite. Therefore, it is possible to conclude that in the concentrations used, this drug caused little alteration in the metabolic pathways of the parasite.
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/9491755585617846
The 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 sector
Análise da diversidade genética e mutações no gene da integrase de isolados do HIV-1 de pacientes atendidos no município de Jataí/Goiás
(Universidade Federal de Goiás, 2018-04-11) Paula, Marcella Silva de; Cardoso, Ludimila Paula Vaz; http://lattes.cnpq.br/5434857923089593; Feres, Valéria Christina de Rezende; Fiaccadori, Fabíola Souza; Cardoso, Ludimila Paula Vaz
INI have been available in Brazil since 2009, when the first INI, Raltegravir, became available for therapy of rescue of HIV + patients in therapeutic failure. In the year 2017, a second INI was introduced into ART of patients newly diagnosed with HIV-1, Dolutegravir, which had a higher genetic barrier and a single daily dose, replaced Efavirenz in the first line of treatment. However, despite the efficiency of INI, the emergence of viral variants resistant to these drugs is inevitable. For this reason, it is necessary to monitor resistance mutations to INI, which may lead to therapeutic failure, aiming at optimizing the therapeutic regimen and controlling HIV infection. The objective of this study was to evaluate the occurrence of INI mutations and the resistance profile in HIV + / AIDS patients in the city of Jataí/Goiás. The complete IN gene was sequenced from samples from INI-naive patients. Resistance mutations were identified by the Stanford-HIV and IAS-USA database. Viral subtypes were identified by phylogenetic analysis. Among the 52 samples analyzed, no primary mutation was identified. Two accessory mutations (T97A / G163K) were identified and these induce a low level of INI resistance. In total, 152 polymorphisms were identified. The most prevalent subtype was subtype B. Therefore, these data demonstrate that the IN region is still highly conserved, encouraging the use of INI in HIV-1 therapy, and assist in the mapping of HIV-1 genetic diversity in the Southwest region of Goiás.
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 Crocco
Introduction: 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.
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 Sichero
Cervical 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.
Análise da proliferação de amastigotas de Leishmania (Viannia) braziliensis em macrófagos murinos
(Universidade Federal de Goiás, 2021-09-30) Teixeira, Mirian Vieira; Oliveira, Milton Adriano Pelli de; http://lattes.cnpq.br/2152513705182408; Oliveira, Milton Adriano Pelli de; Vinaud, Marina Clare; Afonso, Luís Carlos Crocco; Gomes, Clayson Moura; Baeza, Lilian Cristiane
Leishmania (Viannia) braziliensis is the main species responsible for American tegumentary leishmaniasis in Brazil. However, the use of this parasite species to study Leishmania infection in a murine model has been less conducted when compared to other Leishmania species. Control of murine Leishmania infection has been associated with nitric oxide (NO) produced by inducible NO synthase (iNOS) from M1 macrophage, while arginase expressed by M2 macrophages is related to Leishmania proliferation. The aim of this study was to analyze the ability of L. (V.) braziliensis to proliferate within murine macrophages in vitro for a period of 9 days. Macropha-ges were derived from bone marrow precursors (BMDM) of wild-type mice and were cultured with IFN-γ and LPS, or IL-4, or BMDM iNOS knockout (iNOS KO), and nitric oxide production, arginase activity, and infection with L. (V.) braziliensis. The number of infected macrophages and parasite load were determined by light microscopy. Promastigotes of L. (V.) braziliensis parasites were inoculated (106) into the paw of wild-type and iNOS-deficient mice and lesion progression was measured weekly. Wild-type BMDM were observed to not support proliferation of amastigotes of L. (V.) braziliensis strains after day 3 infection, even within IL-4-treated ma-crophages or iNOS KO macrophages. Arginase activity was higher in iNOS KO macrophages than in IL-4 treated macrophages, showing that the absence of proliferation is arginase inde-pendent. L. (V.) braziliensis was able to cause uncontrolled disease in iNOS KO mice in vivo. The data obtained suggest that murine macrophages do not support proliferation of L. (V.) braziliensis amastigotes, even in the absence of nitric oxide and presence of high arginase ac-tivity. Therefore, further studies related to the requirements of amastigotes internalized in host cells are needed, for the search of better methods to interfere in the diversity of leishmaniasis forms caused by different Leishmania spp.
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/1252262903952987
This 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.
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 Souza
Leishmaniasis 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.
Análise das atividades antimicrobiana e citotóxica de actinobactérias isoladas de diversos habitats
(Universidade Federal de Goiás, 2015-03-18) Oliveira, Bruno Francesco Rodrigues de; Vieira, José Daniel Gonçalves; http://lattes.cnpq.br/1742731776579730; Vieira, José Daniel Gonçalves; Ulhoa, Cirano José; Souza, Keili Maria Cardoso de
The actinobacteria constitute a wide and diverse phylum of gram-positive bacteria with a high content of guanine and cytosine in their DNA, standing out by the production of secondary metabolites with antibiotic activity. The treatment of multi-drug resistant pathogens infections and cancer represents a major challenge for modern medicine and bioactive microbial metabolites constitute a rich source of antimicrobial and antitumor drugs. The main aim of this study was to analyse the potential antimicrobial and cytotoxic activities of actinobactéria isolated from various habitats. The evaluation of these bioactivities was accomplished by the application of a set of qualitative screening in vitro assays. From a total of 19 morphospecies, isolated from the goiano Cerrado soil, 16 were evaluated in the primary antimicrobial activity tests, of which 5 (31,25%) antagonized the growth of indicator microorganisms. The ECL of the morphospecie BC-A22 and the crude extracts of the strain ADU 1.3 stood out for their strong antibiotic action against MRSA. The most of the crude extracts exhibited lytic action on the staphylococcal cell wall. Only ECLs of morphospecies GUARA 1 and PEG 23 and extracts of the strain PEG 30 were cytotoxic against A. salina in low concentration. None of the extracts showed an intercalation effect on the DNA molecule. With exception of BC-A22, the other six isolates were morphologically characterized as members of the Streptomyces genus. The morphospecie ADU 1.3 was molecularly identified as Streptomyces sp., highly likely to consist of a new species. The results of this initial phase of microbial bioprospecting highlight that all the isolates are potential producers of antibiotics biomolecules, excelling the morphospecie BC-A22, which exhibited a strong antimicrobial activity against the clinical isolates of MRSA and most of gram-negative bacteria.
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/4434965360286741
Multidrug-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.
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 Melo
Paracoccidioidomycosis 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.
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/4434965360286741
Tuberculosis (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.
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 de
Objectives: 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.

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