Navegando por Assunto "Tuberculose"
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Artigo de Periódico Acesso aberto (Open Access) Abandono do tratamento de tuberculose em co-infectados TB/HIV(2010-06) RODRIGUES, Ivaneide Leal Ataíde; MONTEIRO, Larissa Lima; PACHECO, Régia Hevelline Barros; SILVA, Sílvio Éder Dias daThis study aimed at analyzing the reasons that patients co-infected with tuberculosis and HIV leave the treatment of tuberculosis and to know the conduct of the health team toward that abandonment. The study, using a qualitative approach, performed semi-structured interviews on 45 professionals working at a referral health center in Pará state. Two units emerged based on the thematic analysis: patient-associated factors that make TB treatment adherence difficult; and service-associated factors that contribute to treatment abandonment. It was found that, in terms of the patients, that their low socioeconomic condition was the most common factor that led to abandonment. Other factors that led to this outcome included the adverse drug effects, the use of illegal drugs, and poor personal motivation. Regarding the service, issues related to the physical structure, working process organization and accessibility were also relevant to their non-adherence. Results show there is a need to change the practices performed at the health care services.Dissertação Acesso aberto (Open Access) Acúmulo de colesterol por Mycobacterium smegmatis como possível modulador da biossíntese de lipomanana e lipoarabinomanana(Universidade Federal do Pará, 2015-02-26) SANTOS, Ana Cristina Doria dos; SENA, Chubert Bernardo Castro de; http://lattes.cnpq.br/8620752020290438Mycobacterial cell wall is a hallmark of Mycobacterium genus, constituted of bioactive lipids and glycoconjugates: phosphatidylinositol mannoside (PIMs), lipomannan (LM) and lipoarabinomannan (LAM). The chronic infection inside lung macrophages is related with cholesterol accumulation into host cells as an alternative source of carbon and energy to maintain the bacilli with its physiological functions. To understand the activity of these immunomodulatory glycoconjugates during adaptation under the unusual environment inside the host infected cells, the present work propose to investigate the possible modulation of LM/LAM biosynthesis in Mycobacterium smegmatis (saprophytic) after culture in minimal medium (MM), supplemented with glycerol and/or cholesterol. Our results showed that saprophytic bacilli are able to accumulate the cholesterol and change the bacterial physiology due to slow growth and restrict cell density. Furthermore, the cholesterol consumption decreased the accumulation of PIMs and promoted morphological changes and bacterial aggregates, even maintaining the cell wall with its specific physic-chemistry characteristic (alcohol-acid resistance). The most impressive change after cholesterol consumption was the LAM biosynthesis, which showed distinct electrophoresis migration, compatible to high molecular weight of LAM from non-saprophytic bacilli (from 25 – 30 KDa to 30 – 50 KDa). These results showed that cholesterol consumption, when utilized as principal alternative of carbon and energy source, is able to induce physiological changes in mycobacteria, mainly in LAM biosynthesis, one of the most immunoregulatory molecules of cell wall. Ours data suggest that similar changes in mycobacteria may occur inside the granuloma, and that changes may help the evolution of tuberculosis to chronic and multibacillary form, hallmarked by immunodeficient aspect against the bacilli.Dissertação Acesso aberto (Open Access) Aspectos epidemiológicos, clínicos e evolutivos da tuberculose em idosos de um hospital universitário de Belém - Pará(Universidade Federal do Pará, 2016-02-29) CHAVES, Emanuele Cordeiro; SANTOS, Maria Izabel Penha de Oliveira; http://lattes.cnpq.br/9592128667013030; CARNEIRO, Irna Carla do Rosário Souza; http://lattes.cnpq.br/4389330944043163Physiological changes, especially the immune, make the most vulnerable elderly to infections such as tuberculosis, a disease that this group is specific both in clinical presentation and in its therapeutic management. The objective was to evaluate the epidemiological, clinical and evolutionary aspects of tuberculosis in elderly patients at a university hospital in Belém - Para. It is a study of a retrospective cohort study, conducted at the University Hospital João de Barros Barreto, where 82 records were analyzed of cases of tuberculosis in elderly patients diagnosed from 2009 to 2013, and as a complementary way of obtaining information was obtained from the database of the National System for Notifiable Diseases of the State Department of Public Health. For statistical analysis we used the electronic program Statistical Package for Social Sciences (SPSS) version 22.0, and applied the test G, assuming level α = 0,05 (5%) and value P≤0,05. The study was approved by the Research Ethics Committee of the Tropical Medicine Center under Opinion No. 1.081.347. Most elderly were male (n = 53; 64,6%), aged 60-69 years, both among men (n = 34; 64,2%) and among women (n =13; 44,8%), with a statistically significant difference (p=0,009), new cases of tuberculosis (n = 78; 95,1%), with pulmonary clinical form (n = 62; 75,6%), associated diseases (n = 57; 69,5%) and length of stay greater than 21 days (n = 38; 46,3%). Fever (n = 55; 67,1%), dyspnea (n =53; 64,6%), weight loss (n =50; 61,0%), productive cough (n = 49; 59,8%) and chest pain (n=42; 51,2%) were the primary signs and symptoms evidenced. Regarding treatment, there was a high percentage of adverse events (n=41; 50%), especially gastrointestinal symptoms (n = 29; 70,7%). Most seniors evolved with cure (n = 49; 59,8%), but emphasizes that death from tuberculosis was considerable in the study group (n=13; 15,9%), mainly occurring during hospitalization up 7 days. As for the exposure variables and outcome for healing and death from tuberculosis, there was a statistically significant difference in the age range of variables (p = 0,017), length of stay (p = 0,000) and adverse reactions (p = 0,018). We conclude that the clinical presentation and therapeutic management of tuberculosis in the elderly is different, so it is necessary to strengthen strategies that facilitate early identification of TB suspects elderly in the community, which should take place mainly through Primary.Dissertação Acesso aberto (Open Access) Avaliação externa da qualidade das baciloscopias para tuberculose, realizadas nas unidades laboratoriais públicas no município de Belém (Pará)(Universidade Federal do Pará, 2010-10-04) BRITO, Michele Lima de; LIMA, Karla Valéria Batista; http://lattes.cnpq.br/9795461154139260The sputum examination is the most widely used for diagnosis and control of tuberculosis (TB), as a method of simple execution, low cost, but has low sensitivity and specificity. For the effectiveness and efficiency of this method are met, it is necessary for the establishment and application of standard rules of execution and reading of slides. Thus, it is essential to know the quality of smear microscopy available in a laboratory network. The aim of this study was to evaluate the quality of sputum for diagnosis and control of TB conducted in Units Laboratory (UL) belonging to the public laboratories in Belém, Pará, in 2007, 2008 and 2009. The evaluation was divided into three stages, corresponding to the year of manufacture of the sputum blades. Participants UL 18 that sent regularly to the Central Laboratory of Para, all smear slides prepared by them for External Quality Assessment of Smear (AEQB), which uses the method of blind rereading of smears. This method involves a technical evaluation of the smears, describing them as "Adequate" and "Inappropriate", besides the analysis of discrepant results False Positive (FP) and false negative (FN). During the study period, 4117 samples were processed by UL. In the first stage of evaluation, all 18 UL had blades that were classified as inadequate, and this number decreased to 12 UL in the 2nd stage of evaluation and UL for six at the 3rd step. Regarding disagreements, disagreements had 03 UL 03 UL FP and FN. The results obtained in this study reinforce the need to maintain and expand AEQB for all UL performing smear in the network of laboratories.Artigo de Periódico Acesso aberto (Open Access) Avaliação situacional de biossegurança em tuberculose em Unidades Básicas de Saúde na Amazônia(Universidade Federal do Pará, 2016-12) ARAUJO, Maria Rute de Souza; SILVA, Hilton Pereira da; SILVA, Ariana Kelly Leandra Silva daIntroduction: the research addresses the biosafety of health professionals who attend to tuberculosis (TB) patients in two health care facilities from the Brazilian Amazon - Belém, state of Pará - a school Health Center and a Primary Health Unit (UMS) where most regional TB cases are treated. Objective: to analyze the health professionals’ knowledge on TB biosafety, the infrastructure, the procedures and the TB biosafety resources adopted in these services. Method: a semi-structured interview was conducted with those who deal with the patients, and an observation guide was applied to evaluate the physical structure of the areas specially designated for TB treatment, both based on the TB guidelines of the Brazilian Society of Pneumology and Tisiology. Results: the absence of biosafety measures, as well as the lack of permanent training, compromise the workers’ health. The risk of TB transmission seems to be higher in the UMS due to deficiencies in care organization and to the absence of an adequate environment that could prevent the direct contact of contagious patients with other people. Conclusion: there is an urgent need for changes in the UMS’s workplace and work organization, and also for a permanent TB training program for the health care professionals from both servicesDissertação Acesso aberto (Open Access) Concentrações sanguíneas de pirazinamida e ácido úrico em pacientes em tratamento para tuberculose(Universidade Federal do Pará, 2020-12-7) SOUSA, Alberto Camarão de; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098; https://orcid.org/ 0000-0003-4842-8762Pulmonary tuberculosis is a relevant public health problem in Brazil, where despite the measures of prophylaxis used, there is a high number of cases.The treatment is carried out in two stages: the intensive one, when combined fixed-dose tablets composed of rifampicin, isoniazid, pyrazinamide and ethambutol are administered and the maintenance phase with the use of rifampicin and isoniazid. This is effective in most cases of the disease, however, adverse reactions contribute to non- adherence to treatment, which can lead to therapeutic failure. Pyrazinamide is considered the most hepatotoxic drug, and causes several adverse reactions, such as hyperuricemia, however, few studies have investigated this reaction, which is relevant, because when accompanied by pain symptoms it can lead to treatment abandonment. The aim of this study was to measure plasma concentrations of pyrazinamide, by liquid chromatography of high- performance, and measure the serum acid uric levels, by spectrophotometry, in 44 patients positive by clinical, laboratory, and imaging tests. The measurement assay was done at the end of the intensive treatment phase. Most of the patients were men, with low education and low monthly income. The median daily doses of pyrazinamide administered was 26.2 (22.9-29.7) mg/kg to male patients and 26.8 (23.2-30.8) mg/kg to female. Plasma concentrations of pyrazinamide was 42 (10- 168) µg/mL to men and 50.5 (10-110) µg/mL (P <0.05) in women. The median of plasma concentrations was higher than the minimum inhibitory concentration for sensitive strains of the bacillus. The proportions of patients with serum uric acid levels above the normal range were 75% to female and 44.4% to male, with median values of 7.6 mg/dL and 7.4 mg/dL, respectively. Patient’s weight was not considered as a predictor of plasma pyrazinamide concentrations. The plasma pyrazinamide concentrations and the administered dose, expressed in mg/kg, were not associated with serum uric acid levels. The results of the present study demonstrate that the doses of pyrazinamide provide plasma concentrations that ensure adequate exposure of the bacillus to the drug. Acid uric levels were increased in the patients of this study, probably caused by the metabolites of pyrazinamide.Dissertação Acesso aberto (Open Access) Concentrações séricas de rifampicina e glicemia em pacientes com tuberculose pulmonar ativa(Universidade Federal do Pará, 2019-08-30) FONSECA, Adriana Aparecida Durães; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098; https://orcid.org/ 0000-0003-4842-8762Tuberculosis is a chronic disease caused by Mycobacterium tuberculosis, is considered an important public health issue in Brazil with approximately 70 to 90 thousand cases reported each year. The rates of incidences of chronic comorbidities associated with obesity increased in the last years, and, consequently, the coexistence of tuberculosis and diabetes mellitus also increase. There is an interesting interaction between these chronic diseases, as diabetes mellitus alter the immune response to infection and the pharmacokinetics of anti-tuberculosis drugs, and tuberculosis difficult the glycemic control in patients with diabetes. The aim of the study was to investigate the influence of diabetes mellitus on the serum concentrations of rifampicin in a cohort of patients under treatment with anti-tuberculosis drugs. After fasting of 12 hours, the concentrations of rifampicin, blood glucose levels, and glycated hemoglobin levels were measured at 1h after the ingestion of 600 mg of rifampicin. A total of 49 patients were included in the study and allocated in the TB group (n=36) and TB-DM group (n=13). The dose administered of rifampicin was similar in both groups, with median values of 9,82mg/kg and 10,14mg/kg in TB and TB-DM groups. The median serum concentrations of rifampicin in the intensive phase of treatment were 6,83µg/ml e 2,2µg/ml and in the continuation, were 2,75µg/ml and 2,48µg/ml, in TB and TB-DM groups. Approximately 12,25% of study patients presented rifampicin serum levels above the recommended value (8µg/ml). The concentrations of rifampicin were similar in TB and TB-DM groups in both treatment phases, but TB group present significant high levels of the drug in the acute phase of treatment. Moreover, the concentrations of rifampicin did not correlate significantly with glucose levels and glycated hemoglobin levels in both groups. Diabetes Mellitus did not provoke significant changes in serum rifampicin concentrations, but the treatment phase had a significant impact on drug levels.Dissertação Acesso aberto (Open Access) Determinação das concentrações sanguíneas de pirazinamida em pacientes com tuberculose pulmonar(Universidade Federal do Pará, 2018-04-26) LUCENA, Stefania de Medeiros Araújo; VIEIRA, José Luiz Fernandes; http://lattes.cnpq.br/2739079559531098Tuberculosis is an important health problem in Brazil. The first-line treatment regimen adopted by the Ministry of Health for the treatment of the disease consists of rifampicin, isoniazid, pyrazinamide and ethambutol in the intensive phase (02 months), and rifampicin and isoniazid in the maintenance phase (04 months) of the treatment. The determination of the concentrations of these drugs in biological fluids is determinant to confirm the adequate exposure, besides helping to identify the causes of the multiresistance. In Brazil, the concentrations of these drugs have not yet been described in the course of treatment of the disease. Therefore, this study aims to determine the blood concentrations of pyrazinamide in patients with clinical and laboratory diagnosis of pulmonary tuberculosis, evaluating the influence of sex and hyperglycemia on the plasma levels of these drugs. For this, 54 adult patients of both sexes, diagnosed with active pulmonary tuberculosis, submitted to the first line treatment were included in the study, from which blood samples were collected before treatment (D0), at the end of the first month (D30) and at the end of the second month of treatment (D60). Patients' socio-demographic data were collected through a questionnaire. Pyrazinamide concentrations were determined by high performance liquid chromatography with ultraviolet detection and glycemia by conventional spectrophotometric method. Of the patients included in the study, 53% are male and 90% are between 19 and 59 years old. In addition, 37% completed only elementary education. Eight patients were excluded by noncompliance. The mean plasma concentration of pyrazinamide in pre-dose samples was 3.4 μg / mL and in the post-dose samples it was 72.5 μg / mL. These data point to adequate exposure of M. tuberculosis to the drug. Patients' sex did not influence plasma pyrazinamide concentrations. These results allow us to conclude that the doses of pyrazinamide used in tuberculosis patients caused by M. tuberculosis ensure effective therapeutic blood concentrations in post-dose samples, as well as the pre-dose concentrations were consistent with the pharmacokinetics of the drug. Finally, post-dose concentrations were significantly higher in patients with hyperglycemia.Dissertação Acesso aberto (Open Access) Diagnóstico nutricional de pacientes internados por tuberculose em Belém do Pará(Universidade Federal do Pará, 2004-01-23) CARDOSO, Ana Maria Calabria; SANTOS, Helena; CARDOSO, Ninarosa Calzavara; http://lattes.cnpq.br/8745616558748800; FRAIHA NETO, Habib; http://lattes.cnpq.br/9202245658963683Chronic infectious diseases like tuberculosis are causes of metabolic disturbances, that it interfere in the use and mobilization of corporeal nutrients, affecting the nutritional condition. The immunological function of undernourished sick is altered, which probably incurs in the increased incidence of infectious complications. The research was made to diagnose the nutritional state of patients that were recently - interned with tuberculosis at University Hospital João de Barros Barreto, applying the subjective global assessment technique, verifying the agreement with an objective method, Corporeal Mass Index. It was used the inductive method, that it was descriptive and analytical-descriptive, traverse, having as a reference population the patients that was enrolled on tuberculosis patients group and directed for hospitalization, excluding the patients with tuberculous meningitis. The controlled variables were weight, heigth, sex, forms of tuberculosis, weight alterations, subcutaneous fat, muscle mass, the ingesta of nutrients and the func1ional capacity; presence of gastrointestinal symptoms, signs of edema and ascites. The observed nutritional profile was 77,8% of undernourished, and of these 83,78% moderate and 16,22% serious, with a medium CMI of 18,66 ± 3,86 Kg/m². Most of patients informed weight loss in the last six months before the internment inside of 5% to 10% of his/her habitual weight; 73,82% informed modification on the ingesta of nutrients for smaller amounts and presence of gastrointestinal symptoms in 64,58% of them; being anorexia the most frequent symptom, following by nauseas, vomits and diarrhea; the loss of the functional capacity was a reality in 100% (nurtured and undernourished). In the physical exam it was possible to notice that in 79,16% presented loss of subcutaneous fat and muscular mass simultaneously jointly and no one of the cases presented edema and ascites. The lung tuberculosis was the more incident, being found three cases of ganglial tuberculosis and one with bone tuberculosis associated with Acquired Immunodeficiency Syndrome (AIDS). The CMI in relation to SGA presented a coefficient of Kappa same to 0,47, sensitive validity of 67% and specificity of 100%. SGA was shown as a good applicability technique, demonstrating in practice relatives data, not only of the nutritional state but also in the way of the individuals' life, giving relevant subsidies for the therapeutics into the hospital. The nutritional diagnosis showed a high prevalence so much of undernourished for the subjective method as for the objective and that the concern with the precocious nutritional condition facilitates to an appropriate nutritional intervention. The data suggest to be important the continuity of the study evaluating the nutritional situation to the internment and periodic subsidizing the attendance rendered by the team of health, for the improvement of the health condition in this group of sick.Dissertação Acesso aberto (Open Access) Diminuição da sensibilidade ao contraste espacial de luminância em sujeitos com história de uso de terapia medicamentosa anti-tuberculose(Universidade Federal do Pará, 2012) GOMES, Janildes Maria Silva; SOUZA, Givago da Silva; http://lattes.cnpq.br/5705421011644718The drugs isoniazid and ethambutol, usually administed for tubercolosis treatment, are well known to cause damage in the visual system of the patients that use them. As vision is an important sense for the quality of life and the luminance contrast is considered a good biomarker for visual evaluation, the present study aimed to compare the contrast sensitivity estimated from subjects that used anti-tuberculosis drug therapy and age-matched healthy subjects. The study was performed in Imperatriz city, Balsas city, Davinópolis city and Governador Edson Lobão city, in Maranhão state, Brazil from 2009 to 2012. The current study had a transversal, analytic, and case control profile. Three group of subjects participated from the present study: Control group (n=40), group of subjects treated with isoniazid (n = 19), and group of subjects that used isoniazid associated with ethambutol (n=18). It was used a CRT monitor, 21”, 6 x 5 degrees of visual angle to investigate the contrast sensitivity function. The comparison of the contrast sensitivities at different spatial frequencies among the three studied groups showed statistical differences (Two-way ANOVA, Tukey test, p < 0,05). Control group had higher contrast sensitivity at 10 and 15 cpd than the group that used only isoniazid as drug therapy for tuberculosis treatment and control group had higher contrast sensitivity at 4, 6, 10, 15 and 20 cpd than the group the received isoniazid and ethambutol together. There were no differences between the groups that received anti-tuberculosis therapy.Dissertação Acesso aberto (Open Access) Epidemiologia da tuberculose em crianças menores de 15 anos atendidas nas unidades municipais de saúde(Universidade Federal do Pará, 2003) MIRANDA, Rozinéia de Nazaré Alberto; CORVELO, Tereza Cristina de Oliveira; http://lattes.cnpq.br/7253864056606024; MARTENS, Irland Barroncas Gonzaga; http://lattes.cnpq.br/4404609403033945The tuberculosis in childreen is by definition an indicator of recent transmission and in this case is an alert signal. The object of this study was describe the tuberculosis epidemiologies aspects in childhood. In a register research was colected 80 childreen of 18 Belém's Health Minicipal Unit. It was checked that the age of 10 until <15 years was more attacked by the disease, with significant diferences between the sexes. In antropometric avaliation 17,15% of theses childreen showed low weight in several degrees to the rate W/A . The more frequently tuberculosis symptomatology was in association with the pulmonar clinical form in 77,50% of the childreen. The BAAR and the radiologic were the most important tests to detect the illness, 76,25% of the childreen presented vacinal scar and the bad socioeconomic conditions was a decisive factor to the infectious process. The hard apliccation of the intervention means in disponibility in association with the socio economic's improvement conditions are important. So, this is a protection to avoid that any interruption in the tuberculosis control affect immediately the young people generation.Dissertação Acesso aberto (Open Access) Estratégias educacionais em saúde para mitigar o estigma da tuberculose sofrido pelos pacientes e familiares: revisão integrativa de literatura(Universidade Federal do Pará, 2020-08-24) AZEVEDO, Leyvilane Libdy; GONÇALVES, Lucia Hisako Takase; http://lattes.cnpq.br/6191152585879205; https://orcid.org/0000-0001-5172-7814; POLARO, Sandra Helena Isse; http://lattes.cnpq.br/7875594038005793; https://orcid.org/0000-0001-5026-5080INTRODUCTION: Tuberculosis is an infectious disease, caused by the bacterium Mycobacterium tuberculosis. It is one of the oldest diseases that has received several different meanings according to the historical period. The precarious social conditions of most carriers require commitment, involvement and recognition of their impact on the various dimensions of human life from health services, requiring the perception of these issues and the understanding of their possible influence in the search for health services. OBJECTIVE: The present study aims to analyze educational health strategies aimed at destigmatizing tuberculosis among patients and their families. CONCEPTUAL FRAMEWORK: The concept of Evidence Based Practice and Stigma approached by Goffmann was used as a conceptual framework. METHOD: This is an Integrative Literature Review RIL about studies on educational health strategies aimed at destigmatizing tuberculosis among patients and their families. This was carried out in six stages, namely: elaboration of the research question; sampling; categorization of studies; evaluation of studies; interpretation of results; and presentation of the review. RESULTS AND DISCUSSION: A total of 429 studies were identified, duplicate ones were excluded, resulting in 266 articles. After reading the abstracts and applying the inclusion and exclusion criteria, 40 studies were pre-selected. Of these, 12 were excluded for not being in open access mode. Then, a careful reading of the other articles was carried out, of which 6 were selected to compose the sample of this integrative review. After thorough reading and data collection of the articles included in the IR, the following thematic categories related to the object of study emerged: Stigma, myths and concepts; and Educational health strategies. FINAL CONSIDERATIONS: Based on the results found, educational strategies aimed at patients and family members are pointed out as the best way to reduce stigma in this nucleus. The study pointed out weaknesses regarding the findings that deal with educational strategies aimed at this binomial, since only 6 articles were identified, the majority with a low level of evidence. The low production of Brazilian studies allows a reflection on the need to develop research and broader national discussions on the implementation of strategies with the aim of reducing the stigma associated with the disease.Tese Acesso aberto (Open Access) Estresse oxidativo na hepatotoxicidade aos medicamentos anti-tuberculose(Universidade Federal do Pará, 2016-06-30) COSTA, Maria Heliana Alencar da; MACCHI, Barbarella de Matos; http://lattes.cnpq.br/5330351659478942; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978Tuberculosis treatment involves a combination of drugs with possible interactions with each other and other drugs. The most common side effects are related to hepatotoxicity. The biotransformation of drugs may result in the formation of reactive metabolites that can produce cellular damage which has been considered as an important process in the pathogenesis of hepatotoxicity. Goals: Evaluate the role of oxidative stress in patients with hepatotoxicity that have used anti-TB drugs. Methodology: To reach the first goal a Review of hepatotoxicity as an adverse reaction to anti-TB drugs was performed. Such an review was done through a wide search in the Portal of the Virtual Library of Health that targeted Portuguese and English literature to find papers pub- lished until December 2014. On the other hand, a Case Control study was performed to reach the second goal. For the analysis of antioxidant enzymes, patients treated at HUJBB in Secondary Reference Clinic of Pulmonology Clinic and admitted in línica of Pulmonology, and the patients seen at the Basic Health Unit Guamá in Belém were included. Results: As for the literature review, it was found that hepatic impairment is among the highest incidence of adverse reactions associated with anti-tuberculosis drugs in the Brazilian scene and adverse reactions during treatment of tuberculosis are one of the main factors associated with therapy abandonment. Regarding the analysis of antioxidant enzymes, the analysis of glutathione in the control group with hepatotoxicity (PCH) and the group without hepatotoxicity with anti-TB drugs (PCT) achieved median glutathione levels of 221 nmol / ml, 227 nmol / ml, and 236 nmol / ml, respectively. The distribution of catalase in the control group with hepatotoxicity (PCH) and the group without hepatotoxicity with anti-TB drugs (PCT) showed medians of catalase activity with values of 213 nmol / ml, 319 nmol / ml and 2035 nmol / ml, respectively. The median levels of antioxidants glutathione to the PCT group was the largest. However, glutathione levels were not statistically significant when applying the ANOVA test. Distributions of catalase activity in the population of TB patients in the group who developed hepatotoxicity (PCH) and that evolved without hepatotoxicity (PCT) were larger when compared to healthy volunteers. In particular, there was a statistically significant difference in catalase activity in the group (PCT) compared to the remaining groups. Conclusion: The results suggest that hepatotoxicity is not only associated with antioxidants enzymes and further analysis with more explanatory variables should be made to better understand this phenomenon.Artigo de Periódico Acesso aberto (Open Access) Incidence of tuberculosis among patients with rheumatoid arthritis using TNF blockers in Brazil: data from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro Brasileiro de Monitoração de Terapias Biológicas – BiobadaBrasil)(Universidade Federal do Pará, 2017) YONEKURA, Claudia Leiko Yonekura; OLIVEIRA, Renê Donizeti Ribeiro de; RANZA, Roberto; RANZOLIN, Aline; HAYATA, André Luiz Shinji; SILVEIRA, Inês Guimarães da; CARVALHO, Hellen Mary da Silveira de; MORAES, Julio Cesar Bertacini de; ABREU, Mirhelen Mendes de; VALIM, Valéria; BIANCHI, Washington Alves; BRENOL, Claiton Viegas; PEREIRA, Ivânio Alves; COSTA, Izaias Pereira da; MACIEIRA, José Caetano; GUEDES-BARBOSA, Luiz Sérgio; BERTOLO, Manoel Barros; CUNHA, Maria de Fátima Lobato da; SILVA, Marília Barreto Gameiro; FREIRE, Marlene; SCHEINBERG, Morton Aaron; TOLEDO, Roberto Acayaba de; OLIVEIRA, Sheila Knupp Feitosa de; FERNANDES, Vander; PINHEIRO, Marcelo de Medeiros; CASTRO, Gláucio Ricardo Werner de; VIEIRA, Walber Pinto; BAAKLINI, Cesar Emile; RUFFINO-NETTO, Antonio; PINHEIRO, Geraldo da Rocha Castelar; LAURINDO, Ieda Maria Magalhães; LOUZADA-JUNIOR, Paulo; TITTON, David C.; DUARTE, Angela; MIRANDA, Jose R. S.Objectives: To assess the incidence of tuberculosis and to screen for latent tuberculosis infection among Brazilians with rheumatoid arthritis using biologics in clinical practice. Patients and methods: This cohort study used data from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro Brasileiro de Monitoração de Terapias Biológicas - BiobadaBrasil), from 01/2009 to 05/2013, encompassing 1552 treatments, including 415 with only synthetic disease-modifying anti-rheumatic drugs, 942 synthetic DMARDs combined with anti-tumor necrosis factor (etanercept, infliximab, adalimumab) and 195 synthetic DMARDs combined with other biologics (abatacept, rituximab and tocilizumab). The occurrence of tuberculosis and the drug exposure time were assessed, and screening for tuberculosis was performed. Statistical analysis: Unpaired t-test and Fisher's two-tailed test; p < 0.05. Results: The exposure times were 981 patient-years in the controls, 1744 patient-years in the anti-TNF group (adalimumab = 676, infliximab = 547 and etanercept = 521 patient-years) and 336 patient-years in the other biologics group. The incidence rates of tuberculosis were 1.01/1000 patient-years in the controls and 2.87 patient-years among anti-TNF users (adalimumab = 4.43/1000 patient-years; etanercept = 1.92/1000 patient-years and infliximab = 1.82/1000 patient-years). No cases of tuberculosis occurred in the other biologics group. The mean drug exposure time until the occurrence of tuberculosis was 27(11) months for the anti-TNF group. Conclusions: The incidence of tuberculosis was higher among users of synthetic DMARDs and anti-TNF than among users of synthetic DMARDs and synthetic DMARDs and non-anti-TNF biologics and also occurred later, suggesting infection during treatment and no screening failure.Dissertação Acesso aberto (Open Access) Investigação de polimorfismos no gene TNF em pacientes com hepatotoxicidade induzida por medicações antituberculosas no norte do Brasil(Universidade Federal do Pará, 2015-08-27) VALENTE, Sonia Lopes; SANTOS, Ney Pereira Carneiro dos; http://lattes.cnpq.br/1290427033107137; SORTICA, Vinicius de Albuquerque; http://lattes.cnpq.br/2046482071071824Tuberculosis still remains a serious public health problem worldwide. The hepatotoxicity induced by anti-tuberculosis drugs causes a large number of hospitalizations and may be fatal if treatment is not interrupted. The hepatitis induced by anti-tuberculosis drugs are not yet fully understood and clinical studies suggests that immunological mechanisms are involved in its pathogenesis. The cytokine TNF-α is a major mediator of inflammatory and immune changes in the levels of this cytokine may be related to pathogenesis of drug-induced hepatitis. These changes observed may be related to polymorphisms in the TNF gene. The knowledge of which polymorphisms in the TNF gene are involved in the risk of developing hepatotoxicity anti-tuberculosis drugs will permit the use of these molecular markers to improve the therapeutic management of these patients. This study investigated the influence of polymorphisms -308C>T (rs1800629), -1031C>T (rs1799964), -238A>G (rs361525) and -857C>T (rs1799724) in the TNF gene with drug-induced hepatotoxicity. The study included 68 patients with tuberculosis who had hepatotoxicity of the basic regimen consisting of rifampicin, isoniazid, pyrazinamide and ethambutol (2RHZE/4R) and 191 patients without adverse therapy effects. The polymorphisms were determined by real-time PCR with TaqMan probes. Comparing the frequency of genotypes between cases and controls, a significant difference in the distribution of genotypes of the SNP -1031C>T was identified (p = 0.003). The frequency of homozygous -1031CC was higher in the case group (8.8%) than in the control group (1.6%). The -1031CC homozygous patients had an increased risk for the development of hepatotoxicity when compared to homozygous -1031TT or the T allele carriers (OR = 8.632, p = 0.014, OR = 11.355, p = 0.004). We concluded that -1031C>T SNP was significantly associated with susceptibility to induced hepatitis anti-tuberculosis drugs in the north population of Brazil.Dissertação Acesso aberto (Open Access) Investigação de polimorfismos nos genes IFNɣ e INFGR1 associados à tuberculose no estado do Pará(Universidade Federal do Pará, 2015-11-06) CARNEIRO, Klezzer de Oliveira; SANTOS, Ney Pereira Carneiro dos; http://lattes.cnpq.br/1290427033107137; ASSUMPÇÃO, Paulo Pimentel de; http://lattes.cnpq.br/7323606327039876Pulmonary tuberculosis is an infectious disease transmission by air, which according to the World Health Organization (WHO), infects about two billion people around the world. It is the leading cause of death from infectious disease in adults in developing countries, representing a serious public health problem, mainly due to non-adherence to treatment, late diagnosis and underdiagnosis and no control contacts, which makes our population susceptible to infection. The present study aimed to investigate associations three genetic polymorphisms in IFNɣ and INFGR1 genes responsible for susceptibility to tuberculosis in patients affected by the disease; evaluate if there are differences in allelic and genotypic frequencies of polymorphisms in genes IFNɣ 871A> T, INFGR1 611 (C> T) and INFGR1 -56 (A> G) among individuals with TB and those without TB population of Bethlehem. The control substructures effect was carried out by the use ofa 48 markers Informational Genetic Ancestry panel in both patient sample and the control sample. For this study we used peripheral blood samples from 148 patients diagnosed with tuberculosis, and 125 individuals without tuberculosis (controls) resident in the State of Pará, Brazil, attended at University Hospital João de Barros Barreto (HUJBB) during the period from 2006 to 2012. each specimen was obtained 5 ml of venous blood collected from a peripheral vein. DNA extraction was performed according to the method described by Sambrook et al., (1989). Genotyping for polymorphisms IFNɣ gene (rs1130562) and INFGR1 (rs1327474, rs2234711) was performed by PCR in real time (RTQ-PCR) using the TaqMan system. Statistical analyzes were performed in SPSS 17.0 software, using the Mann- Whitney test, with significance set at p <0.05. The results did not show significance of the polymorphisms investigated in relation to susceptibility to tuberculosis.Dissertação Acesso aberto (Open Access) Investigação do polimorfismo do exon - 1 do gene MBL (Mannose-Binding Lectin) em pacientes portadores de tuberculose(Universidade Federal do Pará, 2009-03-31) ARAÚJO, Mauro Sérgio Moura de; VALLINOTO, Antonio Carlos Rosário; http://lattes.cnpq.br/3099765198910740Mannose-binding lectin (MBL) is considered an acute phase protein with important role in the first line of defense of the innate immune system, whose serum levels are genetically determined. The MBL activates the lectin pathway of complement, and mediate the phagocytosis of microorganisms and opsonization. Several studies have associated serum levels of MBL to susceptibility or resistance to infectious agents including the Mycobacterium tuberculosis, causative agent of human tuberculosis. Aiming to evaluate the occurrence of a possible association between MBL gene polymorphisms and tuberculosis, it was evaluated the frequencies of mutations in exon 1 of MBL gene in a group of 167 TB patients, divided into 3 groups: patients with pulmonary tuberculosis, with extrapulmonary tuberculosis, patients with multiresistant tuberculosis to drugs and the control group with 159 health professionals. The identification of alleles MBL*A, *B, *C and *D was performed by polymerase chain reaction, using specific sequences of primers and subsequent enzymatic digestion. The analysis of allelic and genotypic frequencies of exon 1 did not show any significant difference between patients with tuberculosis and control group (p> 0.05). There were no significant associations between groups of pulmonary tuberculosis, extrapulmonary tuberculosis and multidrug drug among themselves and when connected to the control group. Data from our study showed no evidence of any influence of variations in the exon 1 of MBL gene in active tuberculosis, suggesting that the gene polymorphism has no influence on susceptibility to tuberculosis.Tese Acesso aberto (Open Access) Monitorização terapêutica de fármacos utilizados no tratamento da tuberculose no Brasil(Universidade Federal do Pará, 2018-12-07) ALBERIO, Carlos Augusto Abreu; VIEIRA, José Luiz FernandesTuberculosis continues to be a public health problem throughout Brazil. Several efforts have been made to increase their cure rates, such as the use of the DOTS strategy (Directly Observed Treatment for Short Term) to reduce cases of abandonment and improve adherence to treatment. As a result of the increase in primary resistance to isoniazid, the Ministry of Health modified the therapeutic regimen in 2010, adjusting the doses of isoniazid and pyrazinamide, and adding ethambutol in the intensive treatment phase. Due to the lack of data on serum concentrations of first-line drugs in the brazilian population in this new scheme, this study aimed to determine the serum concentrations of rifampicin, isoniazid and pyrazinamide during treatment and its associations with hematological and biochemical alterations, adverse reactions and clinical outcomes. A prospective cohort study was carried out between september 2013 and november 2016 in two basic health units in the city of Belém (Pará). The most common adverse effects were gastric irritation and pruritus, especially in the intensive phase of treatment and the most frequent clinical outcome was discharge by cure (87.5%). There was a high rate of smear negative (98,90%) in the end of intensive treatment phase. Hematological parameters were determined by automatic cell counter (Cobas 2300®) and biochemical parameters by spectrophotometry (Varian®), which did not present any relevant changes during treatment. The drugs analyzed were rifampicin, isoniazid, and pyrazinamide, and their serum concentrations were determined by reverse phase high performance liquid chromatography (HPLC-RP). Rifampicin and isoniazid presented serum concentrations within the minimum inhibitory concentration (MIC), except for pyrazinamide, which presented values below MIC (3.3 μg/ml), but with a maximum concentration (Cmax) well above the recommended values (63.3 μg/ml). Female patients had higher serum rifampicin concentrations than males. The serum concentrations of rifampicin and isoniazid did not show significant variations between the intensive phase and the maintenance phase. The findings of this study allow us to conclude that the current treatment is safe and effective, since the minor adverse reactions were the most frequent, there were no relevant hematological and biochemical alterations, and the majority of the patients evolved to cure.Dissertação Acesso aberto (Open Access) O papel do colesterol na biossíntese da parede celular de Mycobacterium smegmatis(Universidade Federal do Pará, 2015-02-26) MARINHO, Victor Hugo de Souza; SENA, Chubert Bernardo Castro de; http://lattes.cnpq.br/8620752020290438Different Mycobacterium species are causative agents of disease in humans, for example, the tuberculosis. All mycobacteria have a complex cell wall, distinct of others bacteria, conferring specific physic-chemical characteristic to Mycobacterium genus, due to protect against immune system and waterproofing against the intake of much antibiotics. During infection, the bacillus is able to adapter to harsh environment, due to consumption of cholesterol from itself host cell (macrophages) as alternative carbon and energy source. That nutritional aspect has been considered as essential for division of bacilli and consecutive progress of tuberculosis disease. The present study has as objective to evaluate in vitro the modulation of saprophytic Mycobacterium smegmatis cell wall biosynthesis after cholesterol consumption as primordial energy and carbon source. As results, we are found by Thin Layer Chromatography (TLC) that bacillary adaptation to microenvironment with poor nutrient (minimal media – MM) maintained the biosynthesis and accumulation of essential cell wall components, when the growth occurs in presence of someone defined carbon and energy source (glycerol and/or cholesterol). Among them without changes, we analyzed Trehalose Dimicolate (TDM) and the phospholipids (phosphatidylinositol (PI), phosphatidylinositol manosides (PIMs), Cardiolipin (CL) and phosphatidylethanolamine (PE)). Differently of these results, the micolic acid showed representative accumulation, comparing with 7H9 culture, only when the MM was supplemented with glycerol. This result was confirmed by alcohol-acid staining using fluorescent auroamine dye, suggesting some changes in physic-chemistry cell wall properties. On the other hands, the MM culture induced the accumulation of glycopeptidolipids (GPLs), independently of glycerol/cholesterol supplementation. Such disturbance in cell wall biosynthesis also changed the bacillary hydrophobicity in all MM groups, but does not change the resistance and sensibility to antibiotics. Those results clearly show that cell wall biosynthesis might be modulate during nutritional shortage, and such presence or absence of cholesterol, as occurs during infection, does not significantly change the bacillary physiology to become vulnerable for antibiotics. It suggests that such modulations might also occur during infection, maintaining the bacilli available to develop the tuberculosis diseases.Dissertação Acesso aberto (Open Access) Representações sociais da tuberculose por pessoas com tuberculose e suas implicações para o seguimento do tratamento(Universidade Federal do Pará, 2021-06-28) MOURA, Adriana Alaide Alves; HUARCAYA, Sofia Sabina Lavado; http://lattes.cnpq.br/7107598022816897; SILVA, Sílvio Éder Dias da; http://lattes.cnpq.br/0084512862619143; https://orcid.org/0000-0003-3848-0348Introduction: Tuberculosis remains recognized worldwide as an important problem that involves public health policies, requiring the development of actions aimed at its control, considering humanitarian, economic and public health aspects. For every case of tuberculosis, the directly observed treatment must be carried out, as it is not possible to predict the cases that will adhere to the treatment, and it is necessary to build a bond between the patient and the health professional. This is because another important aspect that permeates the pathophysiological understanding of the disease is related to the psychological and social issues that tuberculosis presents, as it is associated with stigmas and representations anchored in interpersonal relationships. It is in this context that the Theory of Social Representations is applied, as it is understood that understanding the representations built about tuberculosis and its implications for the follow-up of treatment is fundamental for promoting health and combating this disease. Objective: To understand the social representations of people with tuberculosis about the disease and its implications for treatment follow-up. Method: This is a descriptive study, with a qualitative approach, using the Theory of Social Representations as a theoretical basis. The study setting was the municipal health unit of Guamá, District DAGUA, in the city of Belém. People with a positive diagnosis of tuberculosis and undergoing treatment directly observed in the study unit for a period of one month or more participated in the research. quantitative was defined by applying the data saturation technique. Data collection was performed using two techniques: free word association and semi-structured interview. For data analysis, thematic content analysis was used. Results: from the analysis of the data obtained, the registration units converged into three categories, namely: Representations of tuberculosis and its impacts on the diagnosis; the faces of treatment: challenges in terms of follow-up and hope; and Constructions of living with the disease in the family and society. The ways of living with the disease in the daily work, family and social relationships were marked by concerns and practices related to direct contacts or through objects. Suffering is strongly linked to the treatment routine, which implies a radical change in lifestyle, but also figures as a hope for a cure. The family emerges as a welcoming place; however, there is still strong social discrimination and prejudice marking the social representations of tuberculosis. Final Considerations: The impact of the diagnosis, representation and living with the disease can transform daily life, work, family relationships and society. Discrimination and prejudice have an impact on social life, and denote the need to disseminate qualitative information with a view to reconfiguring such representations so that the patient can be better welcomed and included. Nursing as an active team in this care process must remain present and sensitive to the understanding of these various aspects, contexts and representations that surround them, being also active in public health policies, educational actions and scientific research that contribute to quality of assistance and in the reduction of prejudice.
