Role of gut microbiota in infectious and inflammatory diseases

Thousands of microorganisms compose the human gut microbiota, fighting pathogens in infectious diseases and inhibiting or inducing inflammation in different immunological contexts. The gut microbiome is a dynamic and complex ecosystem that helps in the proliferation, growth, and differentiation of epithelial and immune cells to maintain intestinal homeostasis. Disorders that cause alteration of this microbiota lead to an imbalance in the host’s immune regulation. Growing evidence supports that the gut microbial community is associated with the development and progression of different infectious and inflammatory diseases. Therefore, understanding the interaction between intestinal microbiota and the modulation of the host’s immune system is fundamental to understanding the mechanisms involved in different pathologies, as well as for the search of new treatments. Here we review the main gut bacteria capable of impacting the immune response in different pathologies and we discuss the mechanisms by which this interaction between the immune system and the microbiota can alter disease outcomes

Role of gut microbiota in infectious and inflammatory diseases

Thousands of microorganisms compose the human gut microbiota, fighting pathogens in infectious diseases and inhibiting or inducing inflammation in different immunological contexts. The gut microbiome is a dynamic and complex ecosystem that helps in the proliferation, growth, and differentiation of epithelial and immune cells to maintain intestinal homeostasis. Disorders that cause alteration of this microbiota lead to an imbalance in the host’s immune regulation. Growing evidence supports that the gut microbial community is associated with the development and progression of different infectious and inflammatory diseases. Therefore, understanding the interaction between intestinal microbiota and the modulation of the host’s immune system is fundamental to understanding the mechanisms involved in different pathologies, as well as for the search of new treatments. Here we review the main gut bacteria capable of impacting the immune response in different pathologies and we discuss the mechanisms by which this interaction between the immune system and the microbiota can alter disease outcomes

Evaluation of polymorphisms in toll-like receptor genes as biomarkers of the response to treatment of Erythema nodosum leprosum

Erythema nodosum leprosum (ENL) is an inflammatory complication caused by a dysregulated immune response to Mycobacterium leprae. Some Toll-like receptors (TLRs) have been identified as capable of recognizing antigens from M. leprae, triggering a wide antimicrobial and inflammatory response. Genetic polymorphisms in these receptors could influence in the appearance of ENL as well as in its treatment. Thus, the objective of this work was to evaluate the association of genetic variants of TLRs genes with the response to treatment of ENL with thalidomide and prednisone. A total of 162 ENL patients were recruited from different regions of Brazil and clinical information was collected from their medical records. Genomic DNA was isolated from blood and saliva samples and genetic variants in TLR1 (rs4833095), TLR2 (rs3804099), TLR4 (rs1927914), and TLR6 (rs5743810) genes were genotyped by TaqMan real-time PCR system. In order to evaluate the variants’ association with the dose of the medications used during the treatment, we applied the Generalized Estimating Equations (GEE) analysis. In the present sample, 123 (75.9%) patients were men and 86 (53.1%) were in treatment for leprosy during the ENL episode. We found an association between polymorphisms in TLR1/rs4833095, TLR2/rs3804099, TLR4/rs1927914, and TLR6/rs5783810 with the dose variation of thalidomide in a time-dependent manner, i.e.,the association with the genetic variant and the dose of the drug was different depending on the moment of the treatment evaluated. In addition, we identified that the association of polymorphisms in TLR1/rs4833095, TLR2/rs3804099, and TLR6/rs5783810 with the dose variation of prednisone also were time-dependent. Despite these associations, in all the interactions found, the influence of genetic variants on dose variation was not clinically relevant for therapeutic changes. The results obtained in this study show that TLRs polymorphism might play a role in the response to ENL treatment, however, in this context, they could not be considered as useful biomarkers in the clinical setting due small differences in medication doses. A larger sample size with patients with a more genetic profile is fundamental in order to estimate the association of genetic variants with the treatment of ENL and their clinical significance

Monitoria acadêmica de citologia e histologia e patologia humana no curso de enfermagem durante a pandemia de COVID-19: relato de experiência / Academic monitoring of cytology and histology and human pathology in the nursing course during the COVID-19 pandemic: an experience report

Objetivo: Relatar a experiência de monitores da disciplina Citologia e Histologia e Patologia Humana, descrevendo as implicações das primeiras práticas de ensino no ambiente online. Método: Trata-se de um estudo descritivo do tipo relato de experiência que descreve aspectos vivenciados pelos autores, na oportunidade dos encontros realizados para a monitoria da disciplina de Citologia e Histologia e Patologia Humana. As experiências descritas foram vivenciadas por acadêmicos, de diferentes períodos, do Curso de Enfermagem da Universidade Federal do Maranhão, Campus Imperatriz, durante os semestres letivos de 2020.2 e 2021.1, na universidade em questão. A monitoria foi desenvolvida por 6 monitores: 4 do sexo feminino e 2 do sexo masculino. Resultados: Cada monitor ficou encarregado de um grupo de alunos, onde poderiam desenvolver as atividades utilizando as ferramentas e metodologias de sua preferência. Assim, os monitores buscaram estratégias de ensino adequadas às necessidades dos alunos. Isso também propiciou um ambiente de construção coletiva do processo ensino-aprendizagem, onde os alunos foram encarregados de assumir o papel ativo no processo. A plataforma Google Meet e as extensões do Google foram as ferramentas mais utilizadas pela facilidade de manejo. A participação ativa dos alunos no desenvolvimento da monitoria foi de fundamental importância para que se sentissem parte integrante do processo. Desse modo. os alunos tornaram-se participativos e responsáveis por assumir o papel central em seu processo de aprendizagem. Considerações finais: Pode-se concluir a importância do programa de monitoria para o entendimento do conteúdo. Além disso, especialmente nesse momento de ensino remoto, a monitoria foi fundamental para o melhor desenvolvimento das disciplinas

Boletín oficial de la provincia de Santander: Año XXVII Número 119 - 1963 Octubre 04

O Eritema Nodoso Hansênico (ENH) é uma reação inflamatória que afeta pacientes de hanseníase virchowiana e borderline-virchowiana. Trata-se de uma complicação grave da hanseníase decorrente de seu potencial de causar deformidades e incapacidades. Os tratamentos mais utilizados para o ENH no Brasil são talidomida e prednisona, no entanto, a reação é de difícil controle se apresentando de forma recorrente ou crônica. Os pacientes necessitam de regimes prolongados desses medicamentos sendo sujeitos a complicações e manifestação de efeitos adversos. O objetivo desse trabalho foi realizar um estudo farmacogenético buscando avaliar variantes genéticas que possam influenciar na resposta ao tratamento do ENH com talidomida e prednisona. Através de uma revisão de literatura caracterizamos os medicamentos mais utilizados no tratamento para o ENH, descrevendo seus mecanismos de ação, dose e principais efeitos adversos associados. Todos os medicamentos utilizados no tratamento do ENH apresentam restrições de uso. No caso de prednisona e talidomida, ocorre o risco de efeitos adversos como a dependência para a prednisona, e neuropatia periférica e teratogenicidade para a talidomida. Além disso, nenhum medicamento é completamente eficaz na resolução do ENH. Somado a isso se verificou a falta de uma padronização do tratamento com essas drogas e, especialmente no Brasil, a necessidade de um controle mais efetivo desse tratamento principalmente com a talidomida devido à sua teratogenicidade. Foi realizado um estudo farmacogenético buscando identificar perfis genéticos mais susceptíveis a diferenças nas doses de talidomida e prednisona e à manifestação de efeitos adversos. Foram avaliadas amostras de DNA de pacientes de ENH de diferentes regiões do Brasil que usavam talidomida e/ou prednisona em algum momento do tratamento. Os polimorfismos de base única (SNPs) analisados foram de (1) genes envolvidos com metabolismo ou a ação dos medicamentos: genes NR3C1 e ABCB1, no tratamento com prednisona; e os genes TNF e CYP2C19, no tratamento com talidomida; (2) gene CRBN que codifica a proteína Cereblon, um alvo da teratogenicidade da talidomida e associada ao efeito terapêutico da droga no Mieloma Múltiplo (MM); (3) gene TLR-9 que codifica o receptor toll like receptor 9 (TLR-9), associado ao processo 14 inflamatório do ENH. Na análise de genes associados ao metabolismo e ao mecanismo de ação dos medicamentos, foi encontrada uma associação entre o polimorfismo do gene ABCB1 (rs1045642) com a dose de prednisona e entre haplótipos do gene TNF (rs361525/ rs1800629/rs1799724/rs1800630/rs1799964) e o polimorfismo CYP2C19*2 (rs4244285) com a variação da dose de talidomida durante o tratamento. Sugerimos assim que esses genes podem influenciar a resposta ao tratamento do ENH embora esses genes devam ser mais bem avaliados. Na avaliação do gene CRBN, se analisou polimorfismos rs1620675, rs1672770 e rs4183 das regiões flanqueadoras da porção do gene que codifica a região de ligação da proteína com a talidomida. Houve associação entre os polimorfismos rs1620675 e rs4183 e uma menor dose de talidomida no tratamento do ENH. Também houve associação de alelos e haplótipos desse gene com a manifestação de efeitos adversos. A partir desses resultados, sugerimos que Cereblon pode estar associado à eficácia terapêutica da talidomida no ENH, assim como tem sido descrito no MM. As análises do gene TLR-9 sobre as doses de talidomida e prednisona no tratamento do ENH, revelaram uma associação dos haplótipos (rs5743836/rs352140) TG e CG com a dose de prednisona utilizada e com sua variação ao longo do tratamento do ENH. Esses haplótipos possuem o alelo G do polimorfismo rs352140, indicando a influência desse polimorfismo na ação da prednisona no tratamento do ENH. Os resultados obtidos nesse estudo sugerem uma influência farmacogenética no tratamento do ENH uma vez que nós identificamos variantes genéticas de genes relacionados com o metabolismo de prednisona e talidomida ou com o processo inflamatório do ENH. Esse tipo de estudo pode auxiliar na identificação de perfis de melhor resposta ao tratamento do ENH.Erythema Nodosum Leprosum (ENL) is an inflammatory reaction that affects patients of Lepromatous (LL) and Borderline-lepromatous leprosy (BL). It is a serious complication of leprosy due to its potential to cause deformities and disability. The most used treatments for ENL in Brazil are thalidomide and prednisone, however, the reaction is difficult to control and presents as recurrent or chronic. Patients need prolonged regimens of these drugs being subjected to complications and manifestation of adverse effects. The aim of this study was to conduct a pharmacogenetic study to evaluate genetic variants that may influence the response to treatment of ENH with thalidomide and prednisone. Through a review of the literature we characterize the drugs most used in the treatment for ENL, describing its mechanisms of action, dose and main associated adverse effects. All medicines used to treat ENL have restrictions on use. In the case for prednisone and thalidomide, there is a risk of adverse effects such as dependence on prednisone and peripheral neuropathy and teratogenicity for thalidomide. In addition, no medication is completely effective in the resolution of ENL. Moreover, there is a lack of standardization of treatment with these drugs and, especially in Brazil, the need for a more effective control of thalidomide treatment mainly due to its teratogenicity. A pharmacogenetic study was conducted to identify genetic profiles more susceptible to differences in thalidomide and prednisone doses and to the manifestation of adverse effects. DNA samples from ENL patients from different regions of Brazil that used thalidomide and/or prednisone were evaluated at some point in the treatment. The single-base polymorphisms (SNPs) analyzed were from genes involved in different ENL processes: (1) genes associated with the metabolism or action of drugs: NR3C1 and ABCB1 genes, on treatment with prednisone; and the TNF and CYP2C19 genes, on treatment with thalidomide; (2) CRBN gene encoding Cereblon, the target protein of thalidomide teratogenicity and associated with its therapeutic effect in Multiple Myeloma (MM); (3) TLR-9 gene encoding toll receptor-like receptor 9 (TLR-9), associated with the inflammatory process of ENL. In the analysis of genes associated with metabolism and mechanism of action of the drugs, an association between the polymorphism of the ABCB1 gene (rs1045642) with the dose of prednisone and between 16 haplotypes of the TNF gene was found (rs361525, rs1800629, rs1799724, rs1800630, rs1799964) and the CYP2C19*2 polymorphism (rs4244285) with the dose variation of thalidomide during treatment. We thus suggest that these genes may influence the response to ENL treatment although these genes should be better evaluated. In the evaluation of the CRBN gene, polymorphisms rs1620675, rs1672770 and rs4183 from the flanking regions of the gene portion coding for the protein binding region with thalidomide were analyzed. There was an association between polymorphisms rs1620675 and rs4183 and a lower dose of thalidomide in the treatment of ENL. There was also an association of alleles and haplotypes with the manifestation of adverse effects. From these results, we suggest that Cereblon may be associated with the therapeutic efficacy of thalidomide in ENL, as has been described in the MM. Analyzes of the TLR-9 gene on the doses of thalidomide and prednisone in the treatment of ENL revealed an association of the haplotypes (rs5743836 / rs352140) TG and CG with the dose of prednisone used and its variation throughout the ENL treatment. These haplotypes have the G allele of rs352140 polymorphism, indicating the influence of this polymorphism on the action of prednisone in the treatment of ENL. The results obtained in this study show that genetic variants of genes related to the metabolism of prednisone and thalidomide or with the inflammatory process of ENL may influence the treatment of this condition. This type of study can help in the identification of profiles of better response to ENL treatment