RESUMO Contexto: A tuberculose latente (TBL) é uma condição em que o paciente está infectado com Mycobacterium tuberculosis, mas não desenvolve tuberculose (TB) ativa. Existe a possibilidade de ativação da TB após a introdução de anti-TNFs. Objetivo: Avaliar o risco da terapia biológica induzindo TBL durante o tratamento de doenças inflamatórias intestinais (DII) ao longo de 15 anos em uma área de alto risco no Brasil. Métodos: Foi realizado um estudo retrospectivo de um banco de dados de pacientes com DII em uma clínica privada de referência no Brasil. Todos os pacientes foram submetidos a teste de TST e radiografia de tórax antes do tratamento e uma vez por ano após seu início. Os pacientes foram classificados de acordo com a estratificação de Montreal e foram considerados fatores de risco para o desenvolvimento de TB. Resultados: Entre os fatores analisados, a idade e o sexo foram fatores de risco para TBL. Os pacientes com doença de Crohn’ (B2 e P) e colite ulcerativa (E2) apresentaram maior número de casos de TBL com significância estatística, o que também foi observado para usuários de adalimumab e infliximab, em comparação com outros medicamentos, e o tempo de exposição a eles favoreceu significativamente. Outros fatores, como ambiente de trabalho fechado, foram relatados como riscos. Conclusão: O risco da terapia biológica causar TBL é real, por isso os pacientes com DII devem ser monitorados continuamente. Este estudo revela que quanto maior a exposição aos anti-TNFs, maior o risco. Contexto (TBL tuberculosis (TB ativa antiTNFs. antiTNFs anti TNFs. TNFs anti-TNFs Objetivo (DII 1 Brasil Métodos início Resultados analisados Crohn B2 B (B P E2 E (E2 estatística infliximab medicamentos significativamente fechado riscos Conclusão real continuamente antiTNFs, TNFs, (E

ABSTRACT Background: Latent tuberculosis (LTB) is a condition where the patient is infected with Mycobacterium tuberculosis but does not develop active TB. There’s a possibility of tuberculosis (TB) activation following the introduction of anti-TNFs. Objective: To assess the risk of biological therapy inducing LTB during inflammatory bowel diseases (IBD) treatment over 15 years in a high-risk area in Brazil. Methods: A retrospective study of an IBD patients’ database was carried out in a private reference clinic in Brazil. All patients underwent TST testing and chest X-ray prior to treatment, and once a year after starting it. Patients were classified according to the Montreal stratification and risk factors were considered for developing TB. Results: Among the analyzed factors, age and gender were risk factors for LTB. DC (B2 and P) and UC (E2) patients showed a higher number of LTB cases with statistical significance, what was also observed for adalimumab and infliximab users, compared to other medications, and time of exposure to them favored it significantly. Other factors such as enclosed working environment have been reported as risk. Conclusion: The risk of biological therapy causing LTB is real, so patients with IBD should be continually monitored. This study reveals that the longer the exposure to anti-TNFs, the greater the risk. Background (LTB TB Theres There s (TB antiTNFs. antiTNFs anti TNFs. TNFs anti-TNFs Objective (IBD 1 highrisk high Brazil Methods Xray X ray Results B2 B (B P E2 E (E2 significance users medications significantly Conclusion real monitored antiTNFs, TNFs, (E

Abstract Resistant bacterial infections are a major public health problem worldwide, which entails the need to search for new therapeutic agents. In this context, lichens stand out, provided that they are producers of structurally diverse compounds that have attractive biological properties, including antimicrobial activity. Thus, extracts of 12 lichen species were prepared and their potential to inhibit the growth of 5 bacterial strains was evaluated in this work. The chemical compositions of these extracts were examined using TLC and microcrystallization, being the identity of the active compounds in each extract attributed based on the bioautography technique. The most active extracts (and their identified active compounds) were from Cladonia borealis (usnic, barbatic and 4-O-demethylbarbatic acids), Cladina confusa (usnic and perlatolic acids), Stereocaulom ramulosum (atranorin, perlatolic and anziaic acids) and Canoparmelia cryptochlorophaea (cryptochlorophaeic and caperatic acids), with MICs ranging from 7.8 to 31.25 μg/mL, including for resistant clinical strains. MIC values were also obtained for substances isolated from lichens for comparison purposes. A group of four extracts containing usnic acid was analyzed by 1H NMR in order to correlate relative proportion of major metabolites and extracts activity. The less active extracts in this group, in fact, presented low proportion of usnic acid.

Natural and synthetic sulfur-bearing organic compounds have many applications in medicinal chemistry. This article reports the preparation of amphiphilic β-hydroxy sulfides, sulfoxides, and sulfones derived from cardanol and glycerol. Thiolysis of cardanol epoxide 3 with various thiols (4a-4j) in ethanol or water yielded the corresponding β-hydroxy sulfides 5a-5j (61-95%). Treatment with 30% H2O2 in acetic acid at ambient temperature completely converted these products into β-hydroxy sulfoxides 6a-6j and sulfones 7a, 7c-7f, 7h-7j. The synthesized compounds were characterized by 1H nuclear magnetic resonance (NMR), 13C NMR, high-resolution mass spectroscopy (HRMS) and performed the in vitro evaluation antimicrobial activities against standard strains of Staphylococcus aureus and Escherichia coli. Compounds 5a, 5d-5f, and 5h-5j proved moderately active against S. aureus. None of the compounds were active against E. coli. β-Hydroxy-sulfides 5a-5j were also evaluated for antioxidant properties but failed to exhibit significant activity.

Abstract Resistant bacterial infections represent one of the major threats in worldwide health services. In this scenario, plant essential oils are considered promising antimicrobial agents. Therefore, this study aimed to evaluate the antimicrobial potential of Pectis substriata essential oil alone and in combination with antibiotics, against clinical drug-resistant bacterial strains. The essential oil from the plant aerial parts was obtained by hydrodistillation. Antimicrobial activity was assessed against standard and clinical bacterial strains by broth microdilution method, and the synergistic effect was evaluated by checkerboard microtiter assay. The oil alone showed significant activity against clinical Staphylococcus warneri (62.5 µg.mL-1), and was moderately active on Staphylococcus aureus (standard strain) and clinical Staphylococcus intermedius (125 and 250 µg.mL-1, respectively). Synergism was achieved for the combinations of essential oil and ampicillin on S. warneri and of oil and kanamycin on S. intermedius. Additive effects were also observed. This is the first report of the chemical composition of P. substriata essential oil, and the results revealed the presence of compounds with proven antimicrobial activity. The oil proved active against resistant Gram-positive cocci, and showed synergism with antibiotics, revealing its potential use as adjuvant or in the development of new alternative treatments of drug-resistant antimicrobial infections.

The synthesis of novel amino alcohol derivatives based on cardanol and glycerol were achieved in good yields and characterized by 1H and 13C NMR (nuclear magnetic resonance) and MS (mass spectrometry). In addition, we evaluated the in vitro antimicrobial activity against Gram-positive (Staphylococcus aureus, standard and clinical strains), Gram-negative (Escherichia coli) and M. tuberculosis bacterial strains. The bioassay results indicated that four compounds showed activity against S. aureus, including the clinical resistant strain, with MIC (minimum inhibitory concentration) ranging from 3.90 to 15.60 µg mL-1 and M. tuberculosis, with MIC90 (minimum inhibitory concentration required to inhibit the growth of 90% of organisms) ranging from 3.18 to 7.36 µg mL-1.

Os efeitos dos compostos isolados de líquens brasileiros e seus derivados na produção de NO e H2O2 foram estudados utilizando macrófagos murinos na tentativa de desvendar suas possíveis propriedades imunomodulatórias. A citotoxicidade dos compostos foi estudada utilizando o ensaio de MTT. A estimulação dos macrófagos foi avaliada através da determinação de NO (metodologia de Griess) e H2O2 (peroxidase de raíz forte/vermelho de fenol) no sobrenadante de culturas de macrófagos peritoneais de camundongos Swiss. Este estudo demonstrou atividade estimulante de alguns compostos fenólicos e seus derivados na produção de NO e H2O2. A relação estrutura atividade sugere inúmeras direções sintéticas para futuros melhoramentos da atividade imunológica.

The effects of isolated compounds from Brazilian lichens and their derivatives on H2O2 and NO production were studied using murine macrophages as a part of an attempt to understand their possible immunomodulatory properties. The compound cytotoxicity was studied using MTT assay. Macrophage stimulation was evaluated by the determination of NO (Griess assay) and H2O2 (horseradish peroxidase/phenol red) in supernatants of peritoneal macrophage cultures of Swiss mice. This research demonstrated stimulatory activities of some phenolic compounds isolated from lichens and their derivatives on H2O2 and NO production. Structure-activity relationships suggest several synthetic directions for further improvement of immunological activity.

From the lichen Parmotrema lichexantonicum were isolated the depsidone salazinic acid, the xanthone lichexanthone, and the depside atranorin. The two major compounds, salazinic acid and lichexanthone, were selected for structure modifications. Salazinic acid afforded O-alkyl salazinic acids, some of them potentially cytotoxic against tumor cell lines (HCT-8, SF-295 and MDA/ MB - 435). From lichexanthone were obtained norlichexanthone, 3-O-methylnorlichexanthone, 3-O-methyl-6-O-prenylnorlichexanthone, 3,6-di-O-prenyl-norlichexanthone, 3,6-bis[(3,3-dimethyloxyran-2-il)methoxy]-1-hydroxy-8-methyl-9H-xanten-9-one and 3,6-bis[3-(dimethylamine)propoxy]-1-hydroxy-8-methyl-9H-xanten-9-one. The last compound was the most active against S. aureus.