Doutorado em Medicina Tropical e Saúde Pública (IPTSP)
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Item 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 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 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 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 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 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.Item Análise proteômica do fungo Paracoccidioides durante o processo infeccioso em macrófagos(Universidade Federal de Goiás, 2014-06-06) Bonfim, Sheyla Maria Rondon Caixeta; Soares, Célia Maria de Almeida; http://lattes.cnpq.br/8539946335852637; Soares, Célia Maria de Almeida; Bailão, Alexandre Melo; Borges, Clayton Luiz; Casaletti, Luciana; Oliveira, Milton Adriano PelliParacoccidioides is a fungal human pathogen that causes systemic mycosis paracoccidioidomycosis (PCM). Infection occurs via inhalation of fungal propagules by the host and macrophages are important in the initial contention of the fungus through innate mechanisms. In this study, analysis of proteomic profile of yeast cells of Paracoccidioides, isolate Pb18, recovered from infection in macrophages J774 A1 so as to identify molecules that are expressed in this condition and could represent targets for new antifungal therapies. The analysis of differential protein expression could be detected 181 proteins with induction of expression and decreased expression was observed in 245 proteins in Pb18. The data show up regulation of proteins involved in the processes on the alternative carbon metabolism such as gluconeogenesis, beta-oxidation of fatty acids and amino acids catabolism. Proteins with decreased levels of expression include those related to protein synthesis and glycolysis. Aditionally proteins involved in oxidative stress response and cell defense exhibit increased levels of expression such as superoxide dismutase, heat shock proteins, cytochrome c peroxidase and thioredoxins. A mutant was generated to assess the importance of the enzyme cytochrome c peroxidase during infection suggesting involvement in a complex system of protection against oxidative stress, reinforcing role in the survival of the fungus. The proteomic profile of Paracoccididioides sp in response to internalization in macrophages, first described, reflects significant remodeling of fungal metabolism against oxidative stress and highlighting the versatility of the fungus to adapt to the hostile environment of the macrophage seeking new strategies survival.Item Análises transcricionais no processo de adesão por Paracoccidioides brasiliensis e caracterização funcional de adesinas(Universidade Federal de Goiás, 2010-03-11) NOGUEIRA, Sarah Veloso; SOARES, Célia Maria de Almeida; http://lattes.cnpq.br/8539946335852637Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis (PCM), a human systemic mycosis, prevalent in Latin America. Extracellular matrix (ECM) is a complex net where collagens, laminin and fibronectin can be found and, when exposed, is the first site for the fungus adhesion. Our aim was to study genes involved in the adhesion process using Representational Difference Analysis (RDA). RDA is a PCR-coupled subtractive method that allows the isolation of genes differentially expressed in two different cDNA populations. Hence, cDNAs were synthesized from RNAs extracted from P. brasiliensis yeast cells adhered to collagen and fibronectin to identify overexpressed genes. Genes involved in a wide range of cellular process were found and PbCtr3 (cooper transporter) and enolase (PbEno) were chosen to further studies. A synthetic peptide (PbCTR3) and the recombinant enolase (rPbEno) were utilized together with the anti-rPbEno polyclonal antibody in functional analysis with ECM components and plasminogen. The studies suggest that P. brasiliensis enolase, in the surface, is able to generate plasmin from plasminogen by plasminogen activator. Therefore, it was also demonstrated that this protein is secreted and able to promote fungus adhesion and invasion to cells. These findings clearly establish the role of enolase in the patogenicity of P. brasiliensis.Item Aspectos clínicos e moleculares da dengue na epidemia de 2012/ 2013 em Goiânia – GO, Brasil.(Universidade Federal de Goiás, 2015-12-03) Rocha, Benigno Alberto Moraes da; Guilarde, Adriana Oliveira; http://lattes.cnpq.br/9699585709705483; Martelli, Celina Maria Turchi; http://lattes.cnpq.br/5867052489026059; Guilarde, Adriana Oliveira; http://lattes.cnpq.br/9699585709705483; Cunha, Rivaldo Venâncio da; Fiaccadori, Fabíola Souza; Siqueira Júnior, João Bosco; Féres, Valéria Christina de RezendeBackground: Dengue is the fastest growing arbovirosis in the world, infecting almost 390 million people. The dengue virus is the etiological agent of the disease, which has four serotypes (DENV1-4). All serotypes can cause dengue, varying from asymptomatic to severe forms and may lead to death. In Brazil, in 2010, there was the re-emergence of serotype DENV-4 after 28 years. In 2013, it was registered the largest epidemic in history with more than 1.4 million cases and circulation of the four serotypes. In the state of Goiás, Central Region of Brazil, after serotype DENV-4 entry in 2011, for the first time in the region, in 2013, there was a major epidemic which registered more than 10% of the cases in Brazil, more often DENV -4 followed by DENV-1. In this scenario, a study was conducted with the objective to characterize the clinical and molecular profile of patients with dengue; establish if there were associations between clinical and laboratory markers of severity with the infectious virus serotypes; and genetic characterization of the more frequent virus serotype during the 2012/2013 dengue epidemic in Goiânia, Goiás. Methods: A prospective clinical study with suspected dengue patients from eight reference health units (five public, two hospitals and three of secondary level; and three private hospitals) from January 2012 to July 2013 was conducted. The patients were evaluated in three different moments by clinicians who collected clinical and sociodemographic information. Blood sampling for laboratory testing (Hg, AST, and ALT) and confirmatory tests for dengue infection (IgM, IgG, NS1, and RT-PCR) were performed. The gene sequencing of dengue virus type 4 envelope was also carried out. Patients with confirmation of dengue infection were classified according to clinical signs according to the World Health Organization. Principal findings: Six hundred and fifty patients were recruited; 18 were excluded, and 632 were followed. Four hundred fifty-two patients (71.5%) had confirmed infection and 112 (24.8%) were hospitalized. More than 90% were over 15 years of age, and 235 were female (52.0%). In 328 patients, it was possible to classify the type of infection, and 248 (75.6%) of these had a secondary infection. 188 (41.6%) were classified as FD, 238 (52.6%) as DwC and 26 (5.8%) with DG. Compared to those aged xvi over 15 years, spontaneous bleeding, severe abdominal pain and plasma extravasation were more frequent in children under 15 years of age (p <0.05). There was one death of a 16-year-old. During two years of follow-up, viral RNA was identified in 243 (40.5%) of 600 patients evaluated in these tests, where the four serotypes were identified: 91 (37.4%) with DENV-1, 4 (1.6%) with DENV-2, 13 (5.3%) with DENV-3 and 135 (55.5%) with DENV-4. A higher frequency of some symptoms of severity was observed (thrombocytopenia, spontaneous bleeding and severe abdominal pain) in DENV-1 serotype compared to DENV-4. Eighty percent of patients with DENV-4 had a secondary infection. In the phylogenetic study of DENV-4 envelope gene, genotype II was identified. Conclusion: The present study described clinically and molecularly a large dengue epidemic that occurred in a state of Brazil's Central Region, which revealed the concurrent circulation of the four serotypes, the frequency of clinical signs of disease severity in children aged under 15 years and in people with DENV-1 infection. It also identified the current genotype of the most common serotype in the epidemic. These findings should serve as a warning sign for the health authorities because we are experiencing a significant dispersion of serotypes situation worldwide.Item Aspectos comportamentais, bioquímicos e moleculares envolvidos no processo de infecção de Triatoma infestans por Beauveria bassiana(Universidade Federal de Goiás, 2015-07-22) Lobo, Luciana Silva; Pedrini, Nicolás; Luz, Wolf Christian; http://lattes.cnpq.br/1104009511235835; Luz, Wolf Christian; Quintela, Eliane; Arruda, Walquíria; Faria, Marcos; Cravo, PedroTriatoma infestans is the main vector of Chagas disease in Argentina, Bolívia and Paraguai. Beauveria bassiana is effective against all developmental stages of T. infestans. The dynamics of the host infection with B. bassiana has not been well studied yet and more basic research is necessary to elucidate aspects of this interaction. The present study characterized volatile organic compounds (VOC) secreted by T. infestans physically disturbed and infected with B. bassiana employing gas cromatography coupled to mass spectrometry. The expression of genes potentially involved in the biosynthesis of this volatiles (Ti-brnq and Ti-bckdc) was analysed according to the progress of infection with quantitative reverse transcription real-time (qPCR) methodology. The time-related expression of B. bassiana genes envolved in the biosynthesis of fungal toxins (BbtenS, BbbeaS, BbbslS) in nymphs treated with conidia or blastospores was measured, as well as the gene expression levels of insect proteins belonging to the humoral immune response (TiPPO, TiHL, TiDEF) in the same nymphs. Moreover, the influence of conidia on nymphal behavior was analysed. No clear repellent effect of conidia was found. Isobutyric acid was the most abundant VOC found, however, significant effect of the fungal on propionic acid secretion was found 1–3 days after treatment (a.t.). Ti-brnq and Ti-bckdc expression was higher 4 d a.t. than at 10 d a.t. in both conidial concentrations tested, but a significant effect of the time was found only with the first gene. In individuals immersed in the higher conidial concentration the expression of BbtenS and BbbeaS peaked 3 and 12 days a.t. respectively, and 9 days a.t with individuals treated with the lower concentration. In blastospore-injected nymphs, these genes peaked 24 h a.t. and in dead insect exposed in humid chamber. A significant effect of time on the expression of TiPPO in nymphs immersed in both conidial concentrations was found. TiDEF and TiHL peaked 6 days a.t. to both conidial concentration tested. In insects injected with blastospores significant increase in the expression pattern of all genes was found at the lower dose tested. Results emphasized the importance to elucidate better the dynamics of infection of T. infestans with B. bassiana in order to develop biological control estrategies of these vectors with entomopathogenic fungi.Item Atividade da punicalagina em leveduras do complexo Cryptococcus neoformans e de espécies de Candida(Universidade Federal de Goiás, 2017-09-12) Silva, Thaísa Cristina; Silva, Maria do Rosário Rodrigues; http://lattes.cnpq.br/7119226630434725; Silva, Maria do Rosário Rodrigues; Oliveira, Valéria de; Espíndola, Laila Salmen; Costa, Carolina Rodrigues; Bara, Maria Teresa FreitasIntroduction: the high incidence and mortality rate due to fungal infections arouse interest in the search for more effective and less toxic drugs for the treatment of these infections. Medicinal plants represent a promising source of discovery of antifungal agents. Among the medicinal plants, Lafoensia pacari A. St.-Hil (Lythraceae), plant of the cerrado, stands out for having medicinal properties popularly known in Brazil. Punicalagina, a secondary metabolite extracted from L. pacari leaf, has proven biological activities. Objective: in this work the biological activity of punicalagin on yeasts belonging to the Cryptococcus neoformans species complex and Candida species was evaluated. Methods: the in vitro susceptibility of the yeast to the compound punicalagin was verified using the broth microdilution method. The possible mechanism of action was verified by different methods such as: ergosterol assay of the fungal cell membrane, by morphological and ultrastructural analyzes of the yeasts, by flow cytometry (cell cycle, cytoplasmic membrane injury, reactive oxygen species production and loss of the mitochondrial membrane potential). The in vitro cytotoxicity of punicalagin was verified using Balb/c 3T3 cells, A549 lung carcinoma cells and sheep erythrocytes. Results: the punicalagin was able to inhibit yeast growth at concentrations ≤4 μg/mL with minimum fungicidal concentration (CFM) of >256 μg/mL. The punicalagin reduced the ergosterol synthesis of the fungal cell membrane and promoted alterations in the morphology and the cellular arrangement of the yeasts. The action mechanism analyzed by flow cytometry showed alteration of the cell cycle with increase of the G0/G1 phases and reduction of the G2/M phases, interfering in the cellular division of the DNA of the fungal cells. The compound showed low toxicity on the Balb/c cells 3T3, A549 and sheep erythrocytes. Conclusion: the results presented by punicalagin showed that this compound presents low cytotoxicity to the animal cells, with important antifungal activity against the yeasts of the Cryptococcus neoformans species complex and Candida species.Item Atividade larvicida e caracterização molecular dos princípios ativos de Magonia pubescens St.Hil. (Sapindaceae) e de Copaifera reticulata Ducke (Leguminosae), visando ao controle de Aedes aegypti(Universidade Federal de Goiás, 2004-12-02) Silva, Heloisa Helena Garcia da; Silva, lonizete Garcia da; Silva, lonizete Garcia da; Rodrigues Filho, Edson; Santos, Regina Maria Geris dos; Rodrigues, Maria do Rosário; Bezerra, Jose Clecildo BarretoDengue is an acute viral disease of great importance to the public health, and its high incidence in the tropical countries is intimately related to the presence of the main vector, the mosquito Aedes aegypti. Throughout the years, attempts to control the vector have been based on the application of synthetic chemical insecticides, which have already began to produce undesirable effects. The modification of the susceptibility and the emergence of generations resistant mosquitoes besides fast proliferation stimulated studies about the activity of natural products on the larvae of A. aegypti, as an alternative measure for control. In this work, phytochemicals studies were accomplished by larvicidal activity of the plants Magonia pubescens St. Hil. (Sapindaceae) and Copaifera reticulata Ducke (Leguminosae), with the purpose of isolating fractions and/or pure substances with insecticide potential. After collection of peels of the M. pubescens stem and C. reticulata oil-resin in natura, extracts obtained were submitted to bioassays, guided-purification and structural identification. For the larvicidal activity assays, 3rd instar larvae of A. aegypti were used. They were obtained from cyclic colony maintained by ten years, at 28±1°C, 80±5% of relative humidity and 12 h photoperiod. Twenty larvae were used for each concentration and the bioassays were carried out in 5 replicate, in an acclimatized ambient similar to colony growth. Control assays were conducted using the same number of larvae in a dimethylsulphoxide and distilled water solution. The mortality of larvae was measured after 24 and 48 h. Fractions, subfractions and pure substances with larvicidal activity, obtained from those procedures, were monitored chemically through thin layer chromatography and analyzed by 1H nuclear magnetic resonance and 13C, and gas chromatography coupled to mass spectrometry. The identified active substance in the M. pubescens was a tannin (C45H36O18 and molecular mass of 864.77 Da) which presented LC50 of 3.1 ppm; from the C. reticulata the acid 3-acetoxi-labda-8(17),13-dien-15-oic was isolated (C22H34O4, and molecular mass of 362 Da) with LC50 of 0.8 ppm. These two active substances presented lethal concentrations with potential use in the actions to control of the A. aegypti.Item Avaliação bioquímica in vitro do metabolismo energético de cisticercos de Taenia crassiceps expostos a um derivado benzimidazólico, RCB20(Universidade Federal de Goiás, 2015-02-23) Fraga, Carolina Miguel; Castro, Ana Maria de; http://lattes.cnpq.br/9232309971000621; Vinaud, Marina Clare; http://lattes.cnpq.br/1921551651088660; Cruz, Aparecido Divino da; Costa, Tatiane Luiza da; Bezerra, José Clecildo Barreto; Fernandes, Éverton Kort KampHuman infections caused by Taenia spp may be more frequent than they are reported especially if occurred in immunodepressed patients and if the location of the parasites does not involve vital organs. Albendazole is one of the drugs used in the treatment of such infections and its use in mass treatment campaigns may accelerate the resistance development from the parasites both in humans and animal hosts. The aim of this study was to in vitro evaluate the biochemical alterations in T. crassiceps cysticerci after the treatment with a benzimidazolic derivatice (RCB20). The cysticerci were removed from the peritoneal cavity of BALB/c mice with 30 days of infection, macroscopically classified and harvested into 6 well culture plates. 30 cysticerci from each development stage in each well received 5mL of supplemented RPMI culture medium which contained sulfoxide albendazole (ABZSO) (6,5 μM or 13 μM), or RCB20 (6,5 μM or 13 μM). After 24h of culture the cysticerci were removed from the culture medium and both were frozen in liquid nitrogen. Liquid chromatography of high performance and spectrophotometric analysis were performed. It was possible to observe a difficulty in the secretion of substances by the treated cysticerci due to differences in the concentrations of the products dosed from the vesicular fluid and from the culture medium. This was an effect from the mode of action of the drugs which affects the tubulin formation. Regarding the glycolysis it was possible to observe a gradation increase in the secretion/excretion (S/E) of lactate in the treated groups while there was a decrease of this organic acid in the vesicular fluid. As to the energetic metabolism and the citric acid cycle it was possible to observe its traditional sense functioning due to the detection of alf- ketoglutarate. It was possible an increase in the concentrations of citrate, malate, fumarate and succinate in the treated groups. The alternative pathway of energy production such as beta-oxidation of fatty acids and protein catabolism were detected with an increase in the metabolites from those pathways in the treated groups. Therefore we conclude that in spite of not blocking the glucose uptake the drugs influenced its uptake which lead to the use of alternative pathways of energy production. In spite of more soluble and stable the RCB20 formulation did not present a different biochemical effect than ABZSO.Item Avaliação da acurácia de testes imunocromatográficos rK39 no diagnóstico da leishmaniose visceral em pacientes coinfectados com HIV(Universidade Federal de Goiás, 2014-11-21) Silva , Mauro Roberto Biá da; Costa, Carlos Henrique Nery; Oliveira, Milton Adriano Pelli de; http://lattes.cnpq.br/2152513705182408; Oliveira, Milton Adriano Pelli de; Pereira, Ledice Inácia de Araújo; Lino Junior, Ruy de Souza; Dorta, Miriam Leandro; Costa, Carlos Henrique NeryBackground: Visceral Leishmaniasis (VL) is an anthropozoonosis caused by protozoa of the genus Leishmania, especially Leishmania (Leishmania) infantum or Leishmania (Leishmania) donovani. It is present in tropical and subtropical regions and it is considered a neglected disease. The LV diagnosis is dificult, mainly for patients co infected with HIV, because LV paients present atipical clinic forms and the sorology is not trustfull Objectives: The aim of this thesis is to evaluate the accuracy of Immunochromatographic rK39 tests in the diagnosis of Visceral Leishmaniasis in serum and saliva of HIV-co-infected patients Methods: VL suspected patients were treated at the Institute of Tropical Diseases Natan Portela - IDTNP, Teresina, Piauí, Brazil, from March 2011 to October 2012. In addition to the clinical examination, it was performed the IC rK39 test in saliva and blood and also the bone marrow aspiration for parasitological and the PCR-RFLP tests. As routine in the institution, VL suggestive patients were also investigated for HIV. Bone marrow samples were collected for Leishmania research in smear, culture and PCR. For the research of Leishmania spp. in bone marrow aspirate, the Panoptic stain was used (RANYLAB Pharmaceutical Chemistry). The analyses of the stained slides were done in an optical microscope with immersion objective, magnification of 1000x. To perform the bone marrow aspirate culture, the aspirate was cultivated in 3 mL of NNN medium (McNeal, Novy & Nicolle) and 500 μL Schneider medium at 26°C. The search for promastigotes. was performed every seven days in blade - cover slip in an optical microscope. 5 mL were collected from peripheral blood in Vaccutainer® tubes without any anticoagulant in order to obtain the serum. Sera were then aliquoted in cryoassay tubes and kept in a freezer at -70°C. Saliva was collected in 50 mL polypropylene tubes and, in order to increase the amount of saliva, the patients received a piece of Parafilm® for chewing. Saliva was aliquoted in cryoessay tubes and kept in a freezer at -70°C. Results: VL patients who possessed the IC rK39 test with positive serum showed 58.6% of positivity (n = 17) in saliva (SalPos), while all of the healthy donors (CT) (n = 20) were negative in serum and saliva. The amount of total and specific IgG in the serum of patients with VL was significantly higher than that in the CT group. The specific IgG of the SalPos group was greater than in VL patients with negative saliva (SalNeg), but it was not statistically xv significant. The amount of total or specific IgA was similar in all groups. The amount of specific IgG for Leishmania found in saliva of both the SalPos and SalNeg groups was higher than in the control group, but the group with SalPos saliva presented more specific IgG to Leishmania than the SalNeg group. Among the 86 VL patients, 33 had positive serology for HIV and five tested negative serology, however, they were carriers of the virus and were being treated, totalizing 37 infected individuals. The sensitivity of VL in PCR was of 100%, since this test was considered gold standard in this study. The other tests had sensitivity of 57.14% (n = 49) (bone marrow aspiration culture), 48.71% (n = 78) (marrow aspirate smear analysis), 55.81% (n = 86) and 56 25% (n = 85) for the IC rK39 tests in Orangelife or Kalazar Detect serum, respectively. In the case of using the parasitological test as the gold standard, the sensitivity of serological tests was greater than 82%. It is not clear if HIV infection is able to interfere in the serological tests yet. Conclusions: The rK39 IC tests, with the utilization of serum, have a low sensitivity when applied to patients co-infected with HIV and VL, and the use of saliva for VL diagnosis is limited.Item Avaliação da capacidade da nova linhagem de células dendríticas AP284 responder a diferentes agonistas de TLRs e de induzir uma resposta Th17(Universidade Federal de Goiás, 2018-11-14) Oliveira, Pollyana Guimarães de; Oliveira, Milton Adriano Pelli de; http://lattes.cnpq.br/2152513705182408; Oliveira, Milton Adriano Pelli de; Fonseca, Simone; Pfrimer, Irmtraut Araci Hoffmann; Campos, Helioswilton Sales de; Lacerda, Elisângela SilveiraDendritic cells (DCs) are antigen presenting cells (APCs) that belongs a diversify group of cells, being still the main cells that can presents the antigen and activate T lymphocytes by inducing different kinds of cytokine production, which can influence the development of different profiles of lymphocytes. The production of IL-12p70 leads to the Th1 profile differentiation, furthermore the IL-23 production can be important for the establishment and maintenance of Th17 profile. Thus, IL-12 and IL-23 play an important role in the induction or establishment of the adaptive immune response. The aim of the study was characterize the DC AP284 cell line by checking its surface markers, TLRs expression and capacity of response to different TLRs agonists. Besides of that, the production of IL-12p40, IL-12p70, IL-23 and the ability to induce Th1 or Th17 profile were evaluated. AP284 cells have expressed surface molecules compatible with DCs including class II MHC, CD11c and 33D1. After stimulation using different TLRs agonists these cells produced higher amounts of de IL-12p40 and IL-23, but no IL-12p70 production was observed. The IFN-γ addition was not able to induce IL-12p70 production, instead of that an inhibition of the IL-12p40 and IL-23 production were observed. The results have also shown that AP284 cell line is related with the Th17 profile because higher amounts of IL-12p40 and IL-23, but not IL-12p70 were observed, besides of that the results showed an increase in IL-17 levels produced by mice lymph node cells after immunization with Freund’s adjuvant and BCG. Thus, AP284 cells can be important to study the mechanisms of induction and regulation related with the production of IL-12p40 and IL-23 working as a possible tool to study the establishment and maintenance of Th17 cells profile. Moreover, AP284 cells have some similar characteristics among the other immortalized murine DCs, but the AP284 line produces a much higher amount of IL-12p40 than all described cells and is also differentiated among them by the production of IL-23.Item Avaliação da densidade mineral óssea e estimativa de risco de fraturas em homens vivendo com HIV(Universidade Federal de Goiás, 2018-12-17) Sousa, Clarissa Alencar de; Turchi, Marília Dalva; http://lattes.cnpq.br/3769826743537934; Turchi, Marília Dalva; Siqueira Júnior, João Bosco; Teles, Sheila Araújo; Silva, Nilzio Antonio da; Albuquerque, Maria de Fátima Pessoa Militao deEvaluation of bone mineral density and fracture risk estimation in men living with HIV. Introduction: HIV carriers are at increased risk of developing chronic noncommunicable diseases at an early age. The reduction of bone mineral density, before the age of 50 years, is described in this population. Few studies evaluate the magnitude of osteoporosis in men with HIV, as well as screening strategies in this segment. Objectives: To estimate the prevalence and to investigate risk factors for changes in bone mineral density (BMD); compare osteoporosis prediction model, with bone-densitometry as the gold standard; to evaluate the risk of fractures using an algorithm in HIV-positive men. Method: Cross-sectional study, population of men with HIV, over 40 years old, using ART, attended in Goiânia-Goiás. Participants answered a standardized questionnaire, performed clinical evaluation and laboratory tests. All investigated bone mineral density through dual energy X-ray absorptiometry (DXA). Osteoporosis was defined as bone mineral density less than / equal to 2.5 standard deviations (SD), considering as a reference a young, healthy population categorized by sex. Osteopenia was defined as a reduction between 1 and 2.4 SD of bone mineral density according to WHO criteria. The Osteoporosis Self-Assessment Tool (which uses weight and age data) was evaluated in the prediction of osteoporosis and Low BMD. A ROC curve was constructed to assess OST performance. Results: The participants' age ranged from 40 to 72 years, with a mean of 49.6 (SD = 7.5). The prevalence of low bone mineral density was 56.8% (95% CI: 49.25-64, 13%) and osteoporosis 16% (95% CI 11.0 - 22.1). The risk of fractures in 10-years ranged from 1.1% to 20%, with a median of 1.9%. The factors associated with bone density reduction were the use of tenofovir disproxil fumarate and low BMI. The osteoporosis prediction instrument (OST) presented values of area under the curve of 0.71 and 0.67 in the prediction of osteoporosis and low bone mineral density. The cutoff point 7 obtained the best performance in predicting osteoporosis. The instrument revealed low to moderate predictive power over low bone mineral density and osteoporosis compared to DXA. Conclusion: There was a high prevalence of BMD reduction and overweight in a population of relatively young men with HIV.Item Avaliação da modulação da resposta imune induzida por vacina contra tuberculose: rBCG-CMX(Universidade Federal de Goiás, 2016-03-01) Costa, Adeliane Castro da; Kipnis, André; http://lattes.cnpq.br/4434965360286741; Junqueira-Kipnis, Ana Paula; http://lattes.cnpq.br/1252262903952987; Kipnis, Ana Paula Junqueira; Santana, Jaime Martins de; Leite, Luciana Cezar Cerqueira; Stefani, Mariane Martins de Araújo; Celes, Mara Rúbia NunesIn the first chapter of this thesis we demonstrate, in a review article, some of the successful strategies employed in the construction of Bacillus Calmette-Guérin (BCG) vaccines, among others being: overexpression of promising Mycobacterium tuberculosis (Mtb) immunodominant antigens already expressed by BCG introduction of Mtb immunodominant antigens not expressed by BCG, such as antigens in the regions of difference (RD) 1 thru 16; combination of overexpression and introduction of novel antigens to BCG; BCG modification to skew immune response toward TCD8+, as for example recombinant BCG (rBCG) expressing cytokines. In the second chapter, we demonstrate that the recombinant fusion protein CMX is capable of aggregating important immunogenic properties to vaccine vectors, by inducing an effective response for the control of Mtb infection in the mouse tuberculosis infection model. It is hypothesized that the introduction of the rCMX protein in the BCG vaccine could add immunological properties that are absent in BCG, thus leading to the induction of important cell populations for the control of Mtb infection. Our results demonstrate that the introduction of the rCMX in the BCG vaccine, resulting the recombinant BCG vaccine (rBCG-CMX) was an important factor for the observed Th1 and Th17 responses, as well as polyfunctional cells, that could be responsible for the reduced inflammatory lesions seen in the lungs of Mtb infected BALB/c mice, significantly reducing the bacillary load in comparison to in comparison to mice immunized with BCG Moreau vaccine. Lastly, in the third chapter of this thesis we propose that rCMX protein could be responsible for modulating the BCG vaccine to activate a more adequate and protective innate immunity. Our results show that the rBCG-CMX vaccine induces the activation of alveolar macrophages by means of expression of activation-associated molecules CD86 and CD206. The increase in the expression of those molecules are accompanied by the production of TGF-β e IL-1α which in turn could be responsible for the decreased necrosis and higher apoptosis induction promoted by rBCG-CMX vaccination. This phenomenon could be providing a higher cellular survival rate of the recombinant vaccine, leading to a better processing and presentation by MHC-II. As rCMX was shown to induce the production of IL-1α, IL-6 e TGF-β by a pathway that seems to involve the participation of TLR-4, we hypothesize that this recombinant protein could be modulating the BCG vaccine to induce a more appropriate and protectiveresponse for Mtb infection.Item Avaliação da participação de citocinas (interleucina 32, interleucina 10, fator de necrose tumoral) e receptores similares a Toll (TLR 4) na infecção por Leishmania (Viannia) sp.(Universidade Federal de Goiás, 2013-07-26) Galdino Júnior, Hélio; Dias, Fátima Ribeiro; http://lattes.cnpq.br/5741031258926403; Dias, Fátima Ribeiro; Junqueira, Maria Imaculada Muniz Barboza; Shio, Marina Tiemi; Marques, Mara Rubia; Lino Júnior, Ruy de SouzaAmerican Tegumentary Leishmaniasis (ATL) is a disease caused by protozoa Leishmania. In Brazil, the most prevalent species is L. (Viannia) braziliensis. Several cytokines and receptors are involved in immunopathogenesis of ATL, however, the role of interleukin 32 (IL-32) was not investigated in this disease. Besides, toll-like receptors (TLR) were poorly evaluated in Leishmania infection, especially when it is caused by L. (V.) braziliensis. The aim of the present study was to evaluate IL-32, TNF and IL-10 expression in ATL lesions; the induction of IL-32 by L. (V.) braziliensis amastigotes in human peripheral blood mononuclear cells (PBMC) cultures as well as the involvement of TLR4 in monocyte/macrophage response to L. (V.) brazilienis amastigotes. Biopsies fragments from cutaneous and mucosal lesion and healthy tissues were used to investigate the subgenus of the parasites by PCR-RFLP assay; expression of IL-32, TNF and IL-10 was assayed by immunohistochemistry and expression of IL-32 isoforms , TNF and IL-10 was analysed by qRT-PCR. The PBMC were cultured with L. (V.) braziliensis amastigotes in the absence or presence of IFN and IL-32 induction was assayed by qRT-PCR; and TNF and IL-10, by ELISA. TLR4 was neutralized by monoclonal antibodies and lipopolysaccharide (LPS) was used as TLR4 agonist. The expression of TLR4 in monocyte/macrophages was evaluated by flow cytometry. Thirty five patients were evaluated, 23 with cutaneous leishmaniasis (CL) and 12 with mucosal leihsmaniasis (ML). All parasite positive samples contained L. (Viannia) sp. The expression of IL-32 (protein and mRNA) was similar in CL and ML lesions but was higher than in health tissues. Only IL-32 was detected. The proteins TNF and IL-10 were detected in similar levels in CL and ML lesions, but TNF mRNA was present in higher levels in ML (4.069x) than in CL lesions (141 x, p < 0.05). L. (V.) braziliensis amastigotes induced IL-32, TNF and IL-10 in IFN pre-treated PBMC. The production of TNF and IL-10 was TLR4 dependent and treatment of PBMC with LPS further increased the production of TNF induced by amastigotes (p < 0.05). However, LPS did not altere the IL-10 production. Treatment with IFN enhanced the percentage of TLR4+ monocyte/macrophage (p < 0.05), which was decreased following incubation with amastigotes (p = 0.06). The results showed that IL-32 is produced during L. (Viannia) infection and TLR4 mediates L. (V.) braziliensis amastigote-induced TNF and IL-10 production in human PBMC. Moreover, the data suggest that amastigotes can lead to TLR4 internalization what can allow parasite to evade of innate immune response. This study indicates that IL-32 and TLR4 are important players in human infection caused by L. (Viannia), especially L. (V.) braziliensis. Whether TLR4 is also important to IL-32 production by human monocytes/macrophages deserves further investigation.Item Avaliação da resposta imune específica de células TCD8+ e citocinas na tuberculose humana(Universidade Federal de Goiás, 2015-02-13) Silva, Bruna Daniella de Souza; Kipnis, Andre; http://lattes.cnpq.br/4434965360286741; Junqueira-Kipnis, Ana Paula; http://lattes.cnpq.br/1252262903952987; Junqueira-Kipnis, Ana Paula; Bocca, Anamélia Lorenzetti; Souza, Menira Borges de Lima Dias e; Fonseca, Simone Gonçalves da; Stefani, Mariane Martins de AraújoMillions of people die every year due to tuberculosis (TB), an infectious disease that have effective treatment, can be prevented and is curable. One of the greatest problems faced by this disease is the latent infection (LTBI), where individuals do not manifest clinical symptoms, is a reservoir of the causing agent, Mycobacterium tuberculosis (Mtb), and can reactive the disease at any time during their life span. Moreover, TB can affect any organ in the body, such as the skin, causing extrapulmonary TB, a rare form of TB, the TB skin. Some of these forms may be more severe than pulmonary TB, causing serious consequences to the patient, contributing to the high mortality rate of this disease. In this context, understanding the immunological events related to the interaction between pathogen and host the development of active disease or latent infection is a crucial point that can contribute to the control of TB. Thus, the objectives of this study were to evaluate the specific immune response of CD8+ T cells and cytokines in cutaneous tuberculosis, latent and active pulmonary TB. Thirty six patients with pulmonary TB, one patient with cutaneous TB and 36 healthy controls, classified as LTBI (N = 13) or negative (TST-, N = 23) by the tuberculin skin test were recruited and the peripheral blood mononuclear cells, plasma and sera from those individuals were collected to perform flow cytometry, ELISA and multiplex bead array analysis. It was observed that patients with active pulmonary TB presented TCD8+ cells with a regulatory profile, expressing IL-10 and TGF-β in a direct relation to the bacillary load. The same profile was observed in the individual with cutaneous TB, an extra-pulmonary form of TB. The findings observed in this studyco nclude that Mtb can modulate CD8+ T cell response in lung and skin tuberculosis, demonstrating the importance of studies assessing the immune interaction between the pathogen and the host.