Resumo Nanotecnologia é a utilização de materiais na escala nanométrica, em que estes adquirem características próprias. A área de pesquisa e desenvolvimento de novos nanomedicamentos é uma das mais promissoras atualmente, todavia essas partículas necessitam de avaliação particular e ainda não há consenso referente às testagens específicas a serem seguidas, o que dificulta a formação de uma legislação que garanta a segurança e eficácia destes medicamentos, além de um processo de registro mais eficaz. Assim, é necessária uma abordagem bioética da nanotecnologia e sua utilização em medicamentos, visando garantir que o progresso científico não acarrete impactos irreversíveis. Diante dessa problemática, busca-se promover uma discussão nanoética referente ao processo de pesquisa e desenvolvimento de nanomedicamentos, por meio de estudo qualitativo, exploratório-descritivo e de caráter analítico, utilizando revisão bibliográfica, análise documental e dados quantitativos disponíveis como técnicas de pesquisa. nanométrica próprias atualmente seguidas medicamentos eficaz Assim irreversíveis problemática buscase busca se qualitativo exploratóriodescritivo exploratório descritivo analítico bibliográfica

Resumen La nanotecnología utiliza materiales nanométricos, en que estos adquieren características propias. El área de investigación y desarrollo de nuevas nanomedicinas es una de las más prometedoras en la actualidad, sin embargo, estas partículas requieren de una evaluación particular y aún no existe consenso en cuanto a las pruebas específicas que seguir, lo que dificulta establecer una legislación que garantice la seguridad y eficacia de estos medicamentos, además de un proceso de registro más efectivo. Por lo tanto, se necesita un enfoque bioético de la nanotecnología y su uso en medicamentos para garantizar que el avance científico no tenga impactos irreversibles. Ante esta problemática, se pretende promover el debate sobre la nanoética en el proceso de investigación y desarrollo de nanomedicinas a partir de un estudio cualitativo, exploratorio-descriptivo y analítico, que utiliza como técnicas de investigación la revisión bibliográfica, el análisis de documentos y los datos cuantitativos disponibles. nanométricos propias actualidad embargo seguir efectivo tanto irreversibles problemática cualitativo exploratoriodescriptivo exploratorio descriptivo analítico bibliográfica disponibles

Abstract Nanotechnology consist of using materials at the nanoscale, in which they acquire specific characteristics. Nanodrug research and development is one of the most promising fields today; however, these particles require particular evaluation. Moreover, studies lack consensus on which specific tests to follow, thus hindering the elaboration of legislation that ensure their safety and efficacy, as well as a more effective registration process. Thus, a bioethical approach to nanotechnology and its use in drug development is necessary to ensure scientific progress without irreversible impacts. Given this scenario, this article proposes a nanoethics discussion regarding nanodrug research and development by means of a qualitative, exploratory and descriptive analysis, based on literature review, documental analysis and quantitative data available. nanoscale characteristics today however evaluation Moreover follow efficacy process Thus impacts scenario qualitative review available

SUMMARY OBJECTIVE: Bronchiectasis is a chronic respiratory disease characterized by inflammation, irreversible dilation of the bronchi, and recurrent pulmonary infections, with a high morbidity and mortality rate, but is less studied from the point of view of its prevalence and associated factors not directly related to respiratory prognosis. As it is a disease related to the exacerbation of the inflammatory process and oxidative stress, this study searched to investigate the micronucleus frequency in patients with and without bronchiectasis treated at a specialized pulmonology service in a hospital in the extreme south of Brazil. METHODS: Patients with a confirmed tomographic diagnosis of bronchiectasis were defined as cases. Mutagenicity was evaluated by the micronucleus test in patients’ oral mucosa cells. Data collection was performed through a questionnaire containing socioeconomic, demographic, lifestyle, and health condition information. RESULTS: Of the 95 patients involved in this study, 21 (22.1%) were diagnosed with bronchiectasis aged between 12 and 89 years. There was no significant difference in the frequency of micronucleus between patients with and without bronchiectasis. There was a significant positive association between age and frequency of micronucleus among patients with bronchiectasis, but this association does not occur among patients without the disease. CONCLUSION: This is the first study to investigate data on the prevalence and clinical and epidemiological aspects of this chronic disease in Brazil, especially those related to the genotoxicity outcome.

Resumen: Objetivo: Evaluar la morbimortalidad de las bronquiectasias, su interface con el mantenimiento de las tasas de ingreso hospitalario y los resultados pronósticos insatisfactorios, y el impacto negativo en la salud pública brasileña. Métodos: Las informaciones clínicas y epidemiológicas provinieron del departamento de informática del Sistema Único de Salud de Brasil - DataSus, del cual se filtraron los datos requeridos a través de la lista de morbilidades del SUS - CID10. Se buscó información sobre la hospitalización de pacientes con bronquiectasias, como sexo, edad, tiempo y costo de la hospitalización, régimen de tratamiento y número de muertes a consecuencia de la enfermedad. Resultados: Se observó que de enero de 2008 a febrero de 2020 se hospitalizaron alrededor de 24.087 pacientes con bronquiectasias. El 65% eran adultos, con una gran porción en la fase productiva. El 84% de los pacientes buscó unidades de salud en modalidad de emergencia y el 47% acudió a los servicios públicos. El promedio brasileño de estancia hospitalaria fue estimado en 8,1 días, el costo del servicio rondaba los R$ 28 millones y se registraron 698 muertes por bronquiectasias. Conclusiones: Enfermedades como las bronquiectasias están lejos del manejo adecuado que requieren las enfermedades pulmonares crónicas. A pesar de la importante evolución diagnóstica, la etiología y el tratamiento de la enfermedad siguen siendo cuestionables.

Abstract: Objective: To evaluate the morbidity and mortality of bronchiectasis, its interface with the maintenance of hospitalization rates and unsatisfactory prognostic outcomes, as well as the negative impact on Brazilian public health. Methods: The clinical and epidemiological information came from the IT department of the Brazilian Unified Health System - DataSus, from which the required data was filtered through the SUS - CID10 list of morbidities. Information was sought, in absolute numbers, regarding the hospitalization of bronchiectasis patients, such as gender, age, time and cost of hospitalization, care regime, and the number of deaths due to the disease. Results: From the variables found, it was noted that in the period from January 2008 to February 2020, around 24,087 bronchiectasis patients were hospitalized. 65% of the total number of hospitalizations due to the disease consisted of adults, with a large portion in the productive phase (between 20 and 79 years). 84% of the patients sought health units in an emergency mode and 47% used public services at the time of hospitalization. The Brazilian average length of stay in hospital was estimated at 8.1 days and the cost of the service was around R$ 28 million in the twelve years analyzed. Besides, 698 deaths due to bronchiectasis were recorded in Brazil. Conclusions: Diseases such as bronchiectasis are far from the adequate management that chronic lung diseases require. Despite the significant diagnostic evolution, the etiology and treatment of disease is still questionable, providing unsatisfactory quality of life for bronchiectasis patients.

ABSTRACT Background: Tuberculosis (TB) remains a serious public health problem, with approximately 10 million new cases reported annually. Knowledge about the quantitative evolution of theses and dissertations (T&Ds) examining human TB in Brazil can contribute to generating strategic planning for training professionals in this field and disease control. Therefore, this study highlights the role of T&Ds on TB in national scientific disclosures. Methods: An integrative review related to TB was performed, including T&Ds produced in Brazil and completed between 2013 and 2019. Results: A total of 559,457 T&Ds were produced, of which 1,342 were associated with TB, accounting for 0.24% of the total number of T&Ds in Brazil. This was evidenced by a predominance of themes such as attention/health care, epidemiology, and TB treatment, and 80.2% of the T&Ds on TB were related to the large areas of health and biological sciences. Only 19.7% of T&Ds were associated with groups of patients considered at risk for TB, and 50.9% were produced in southeastern Brazil. The 1,342 T&Ds on TB were developed in 416 postgraduate programs linked to 121 higher education institutions (HEIs). We highlight that 72.7% of T&Ds on TB were produced in federal HEIs, 27.4% in state HEIs, and 8.5% in private HEIs. Conclusions: Strategic themes, such as TB control, require public policies that aim to increase the number of doctors and masters with expertise in TB, with geographic uniformity, and in line with the priorities for disease control.

Abstract Sporothrix spp. are the major dimorphic fungus associated with a type of subcutaneous mycosis, sporotrichosis. The limitation of antifungal availability and the past reports of in vitro resistance of Sporothrix spp. clinical isolates makes it important to search for new compounds with antifungal activities. In this study, we therefore evaluate the in vitro activities of complexes coordinated with Co(II) and cobalt chloride hexahydrate against clinical isolates of Sporothrix spp. Broth microdilution test was performed as per M38-A2 from CLSI (2008) in duplicate for 31 clinical isolates of Sporothrix spp. (27 S. brasiliensis e 04 S. schenckii stricto sensu). The antifungal activities of the complexes coordinated with Co(II) and cobalt chloride hexahydrate were detected at a concentration range of 32-128 µg/mL for all isolates. None of the compounds demonstrated any cytotoxicity (to macrophage cells) at the concentration of 200 µg/mL. The activity against Sporothrix spp. recorded in this study instigate the continuity of experimental studies with Co(II) to search for the mechanisms of antifungal action as well as to evaluate its interaction with the commercial antifungal drugs.

Resumo Os produtos naturais têm sido apontados como ferramentas importantes devido ao seu vasto potencial para o desenvolvimento de compostos com atividade antimicrobiana e a possível atividade inibitória e/ou adjuvante de mecanismos de resistência. O própolis é utilizado empiricamente há muitos anos no tratamento de doenças, principalmente devido às suas atividades antioxidantes, anti-inflamatórias e antimicrobianas. Este estudo teve como objetivo avaliar a atividade antimicobacteriana in vitro do extrato etanólico de própolis isoladamente e em associação com rifampicina (RIF), amicacina (AMI) e ciprofloxacina (CIP). O extrato etanólico de própolis mostrou atividade antibacteriana frente Mycobacterium chelonae e M. kansasii e foi capaz de aumentar a atividade de AMI, RIF e CIP em associação. Por outro lado, frente a M. absecessus, M. fortuitum e M. avium, o extrato não foi ativo a 200 µg/mL e não apresentou capacidade adjuvante pronunciada quando avaliado em associação com os fármacos. Com base nesses resultados, pode-se concluir que o extrato etanólico de própolis pode ser uma alternativa no desenvolvimento de novos fármacos e pode ser utilizado complementarmente com o atual tratamento das micobacterioses.

Abstract Natural products have been touted as important tools because of their vast potential for the development of compounds with antimicrobial activity and the possible inhibitory activity and/or adjuvant resistance mechanisms. Propolis has been empirically used for many years for the treatment of diseases, mainly due to its antioxidant, anti inflammatory and antimicrobial activities. This study aimed to evaluate the in vitro antimycobacterial activity of the ethanol extract of propolis alone and in combination with rifampicin (RIF), amikacin (AMI) and ciprofloxacin (CIP). The ethanol extract of propolis showed antibacterial activity against Mycobacterium chelonae and M. kansasii and was capable of increasing AMI, RIF and CIP activity in combination. On the other hand, compared to M. absecessus, M. fortuitum and M. avium, the extract was not active at 200 µg/mL and did not show pronounced adjuvant capacity when evaluated in association with the drugs. Based on these results, it can be concluded that the ethanol extract of propolis could be an alternative in the development of new drugs and can be used complementary with the current mycobacteriosis treatment.

Resumo Duroia saccifera (Rubiaceae) ocorre na floresta Amazônica. Seus extratos apresentaram atividade antibacteriana. Para obter maiores quantidades de substâncias ativas, foram utilizados segmentos de folhas de plântulas in vitro de D. saccifera como explantes para indução de calos; os calos foram multiplicados através de múltiplos subcultivos, depois secos e extraídos com hexano, seguido por acetato de etila (AcOEt) e metanol (MeOH). Como D. macrophylla foi relatada como produtora de substâncias antimicobacterianas, os extratos de calos foram testados contra Mycobacterium tuberculosis (cepa H37Rv). O extrato AcOEt dos calos foi ativo, com uma concentração inibitória mínima (CIM) de ≤ 25 mg mL-1, IC90de 19,5 mg mL-1 e concentração bactericida mínima (MBC) de 200 mg mL-1. O extrato AcOEt foi analisado por cromatografia em camada delgada comparativa (CCDC) e Ressonância Magnética Nuclear (RMN) para determinar o seu perfil químico e mostrou ser rico em terpenos. O fracionamento cromatográfico do extrato AcOEt conduziu ao isolamento de uma mistura de dois esteroides, β-sitosterol e estigmasterol (na proporção de 2:1), os quais foram identificados por análises de RMN de 1H e bidimensionais. Pelo levantamento bibliográfico realizado, este é o primeiro relato da cultura de células in vitro de Duroia saccifera, da atividade antituberculose do extrato de calos e do isolamento de β-sitosterol e estigmasterol da cultura de células vegetais in vitro da espécie.

Abstract Duroia saccifera (Rubiaceae) occurs in the Amazon rainforest and their extracts showed antibacterial properties. To obtain greater quantities of active substances, leaf segments from in vitro D. saccifera seedlings were used as explants for calli induction; calli were multiplied via multiple subcultures, dried and extracted with hexane followed by ethyl acetate (EtOAc) and methanol (MeOH). As D. macrophylla had been reported to produce antimycobacterial substances, we assayed calli extracts against Mycobacterium tuberculosis (H37Rv strain). Calli EtOAc extract was active, with a minimal inhibitory concentration (MIC) of ≤ 25 mg mL-1, IC90of 19.5 mg mL-1 and minimal bactericidal concentration (MBC) of 200 mg mL-1. EtOAc extract was analyzed by Thin Layer Chromatography (TLC) and Nuclear Magnetic Resonance (NMR) to determine its chemical profile, and was found to be rich in terpenes. Chromatographic fractionation of the EtOAc extract yielded a mixture of two sterols, β-sitosterol and stigmasterol (in proportion of 2:1), which were identified by 1H and 13C NMR analysis. As far as we know, this is the first report of Duroia saccifera in vitro cell culture, antituberculosis activity of calli extract and β-sitosterol and stigmasterol isolation from in vitro plant cell culture.

ABSTRACT In this study, we evaluated the mutations of Helicobacter pylori associated with resistance to clarithromycin and levofloxacin. Furthermore, based on the proposed interaction between antimicrobial resistance and pathogenicity, we correlated the mutation profiles of the strains with the presence of the pathogenicity gene cagA. We analyzed 80 gastric biopsy specimens from H. pylori-infected patients for point mutations in the 23S rRNA gene region and in the gyrA gene, which are related to clarithromycin and levofloxacin resistance, respectively, and investigated the presence of the cagA gene in these strains. We observed that in the assayed biopsies, 8.7% (7/80) had mutations in the 23S rRNA gene region at positions 2143 and 2142, while 22.5% (18/80) had mutations in gyrA at codons 87 and 91. Moreover, absence of the CagA-EPIYA pathogenicity factor was observed in 68% (17/25) of resistant samples. The knowledge of the local profile of antimicrobial resistance and the complex interplay involving resistance and pathogenicity can contribute to an appropriate clinical approach.

RESUMO Contexto Helicobacter pylori tem uma distribuição a nível mundial, e está associado a patogênese de várias doenças do sistema digestivo. O tratamento para a erradicação deste microrganismo envolve a utilização de uma combinação de agentes antimicrobianos, tais como amoxicilina, metronidazol, claritromicina e levofloxacino, combinados com inibidores da bomba de prótons. Embora a terapia atual seja eficaz, uma elevada taxa de fracasso de tratamento tem sido observada, principalmente devido à aquisição de mutações pontuais, um dos principais mecanismos de resistência desenvolvida por H. pylori, relacionado com o uso frequente e/ou inadequado dos antibióticos. Conclusão Esta revisão abordou uma visão geral da resistência às principais drogas utilizadas no tratamento de H. pylori, confirmando a hipótese de que a resistência bacteriana é um fenômeno altamente local e as características genéticas de uma dada população podem influenciar qual terapia é a mais apropriada.

ABSTRACT Background Helicobacter pylori has a worldwide distribution and is associated with the pathogenesis of various diseases of the digestive system. Treatment to eradicate this microorganism involves the use of a combination of antimicrobials, such as amoxicillin, metronidazole, clarithromycin, and levofloxacin, combined with proton pump inhibitors. Although the current therapy is effective, a high rate of treatment failure has been observed, mainly because of the acquisition of point mutations, one of the major resistance mechanisms developed by H. pylori. This phenomenon is related to frequent and/or inappropriate use of antibiotics. Conclusion This review reported an overview of the resistance to the main drugs used in the treatment of H. pylori, confirming the hypothesis that antibacterial resistance is a highly local phenomenon and genetic characteristics of a given population can influence which therapy is the most appropriate.

Abstract: INTRODUCTION: The World Health Organization endorses the BACTEC Mycobacterial Growth Indicator Tube (MGIT)(tm) system as a rapid, sensitive, and specific method to diagnostic of tuberculosis. Here, we compared the performance of this system against Ogawa-Kudoh cultures and microscopy. METHODS: A total of 927 samples were obtained between December 2011 and December 2013 from 652 cases of suspected tuberculosis at the School Hospital of the Federal University of Rio Grande in Brazil. RESULTS: The MGIT system confirmed tuberculosis in more cases in less time. CONCLUSIONS: The MGIT system is an effective tool for early diagnosis of tuberculosis, especially in patients with HIV/AIDS.

Background The present work aimed to evaluate the antimycobacterial activity and cytotoxicity of Microcystis aeruginosa toxins, the MC-LR variant and purified extract of [D-Leu1] microcystin-LR. Methods The antimicrobial activity of M. aeruginosa extract and microcystin was evaluated by resazurin microtiter assay against Mycobacterium tuberculosis, M. terrae, M. chelonae and M. kansasii. The cytotoxicity assay was performed by trypan blue exclusion against the HTC cell line. Results Antimicrobial activity was observed in the hexanic extract of M. aeruginosa (RST 9501 strain) against M. tuberculosis, including sensitive and resistant strains with minimal inhibitory concentrations (MIC) between 1.93 μM and 0.06 μM. The high activity of M. aeruginosa hexanic extract could be attributed to the major presence of the toxins MC-LR and [D-Leu1] MC-LR that showed activity at MIC between 53 and 0.42 μM against tested mycobacterial strains. Even at the highest concentration tested, no toxicity of M. aeruginosa extracts was identified against HTC cells. Conclusions These preliminary results suggest that [D-Leu1] MC-LR is a promising candidate for the development of a new antimycobacterial agent.

Mycobacterium bovis is the main causative agent of animal tuberculosis (TB) and it may cause TB in humans. Molecular typing of M. bovis isolates provides precise epidemiological data on issues of inter- or intra-herd transmission and wildlife reservoirs. Techniques used for typing M. bovis have evolved over the last 2 decades, and PCR-based methods such as spoligotyping and mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) have been extensively used. These techniques can provide epidemiological information about isolates of M. Bovis that may help control bovine TB by indicating possible links between diseased animals, detecting and sampling outbreaks, and even demonstrating cases of laboratory cross-contamination between samples. This review will focus on techniques used for the molecular typing of M. bovis and discuss their general aspects and applications.

Bovine tuberculosis is a major infectious disease of the cattle. In this study, 85 M. bovis isolates from 162 lymph nodes, obtained from a herd of cattle on a farm in southern Brazil, were evaluated using spoligotyping and VNTR. The strains were grouped into five clusters and five orphans, showing a heterogenic genetic profile, what could represent diverse geographic origins of the introduced cows and/or the frequent movement of cattle between different properties.

The development of diagnostic tests which can readily differentiate between vaccinated and tuberculosis-infected individuals is crucial for the wider utilization of bacillus Calmette-Guérin (BCG) as vaccine in humans and animals. BCG_0092 is an antigen that elicits specific delayed type hypersensitivity reactions similar in size and morphological aspects to that elicited by purified protein derivative, in both animals and humans infected with the tubercle bacilli. We carried out bioinformatics analyses of the BCG_0092 and designed a diagnostic test by using the predicted MHC class I epitopes. In addition, we performed a knockout of this gene by homologous recombination in the BCG vaccine strain to allow differentiation of vaccinated from infected individuals. For that, the flanking sequences of the target gene (BCG_0092)were cloned into a suicide vector. Spontaneous double crossovers, which result in wild type revertants or knockouts were selected using SacB. BCG_0092 is present only in members of the Mycobacterium tuberculosis complex. Eight predicted MHC class I epitopes with potential for immunological diagnosis were defined, allowing the design of a specific diagnostic test. The strategy used to delete the (BCG_0092) gene from BCG was successful. The knockout genotype was confirmed by PCR and by Southern blot. The mutant BCG strain has the potential of inducing protection against tuberculosis without interfering with the diagnostic test based on the use of selected epitopes from BCG_0092.