Interaction of Mycobacterium leprae with the HaCaT human keratinocyte cell line: new frontiers in the cellular immunology of leprosy.

Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae affecting the skin and peripheral nerves. Despite M. leprae invasion of the skin and keratinocytes importance in innate immunity, the interaction of these cells in vitro during M. leprae infection is poorly understood. Conventional and fluorescence optical microscopy, transmission electronic microscopy, flow cytometry and ELISA were used to study the in vitro interaction of M. leprae with the HaCaT human keratinocyte cell line. Keratinocytes uptake of M. leprae is described, and modulation of the surface expression of CD80 and CD209, cathelicidin expression and TNF-α and IL-1ß production of human keratinocytes are compared with dendritic cells and macrophages during M. leprae interaction. This study demonstrated that M. leprae interaction with human keratinocytes enhanced expression of cathelicidin and greatly increased TNF-α production. The highest spontaneous expression of cathelicidin was by dendritic cells which are less susceptible to M. leprae infection. In contrast, keratinocytes displayed low spontaneous cathelicidin expression and were more susceptible to M. leprae infection than dendritic cells. The results show, for the first time, an active role for keratinocytes during infection by irradiated whole cells of M. leprae and the effect of vitamin D on this process. They also suggest that therapies which target cathelicidin modulation may provide novel approaches for treatment of leprosy.

Interaction of an opportunistic fungus Purpureocillium lilacinum with human macrophages and dendritic cells.

INTRODUCTION: Purpureocillium lilacinum is emerging as a causal agent of hyalohyphomycosis that is refractory to antifungal drugs; however, the pathogenic mechanisms underlying P. lilacinum infection are not understood. In this study, we investigated the interaction of P. lilacinum conidia with human macrophages and dendritic cells in vitro. METHODS: Spores of a P. lilacinum clinical isolate were obtained by chill-heat shock. Mononuclear cells were isolated from eight healthy individuals. Monocytes were separated by cold aggregation and differentiated into macrophages by incubation for 7 to 10 days at 37°C or into dendritic cells by the addition of the cytokines human granulocyte-macrophage colony stimulating factor and interleukin-4. Conidial suspension was added to the human cells at 1:1, 2:1, and 5:1 (conidia:cells) ratios for 1h, 6h, and 24h, and the infection was evaluated by Giemsa staining and light microscopy. RESULTS: After 1h interaction, P. lilacinum conidia were internalized by human cells and after 6h contact, some conidia became inflated. After 24h interaction, the conidia produced germ tubes and hyphae, leading to the disruption of macrophage and dendritic cell membranes. The infection rate analyzed after 6h incubation of P. lilacinum conidia with cells at 2:1 and 1:1 ratios was 76.5% and 25.5%, respectively, for macrophages and 54.3% and 19.5%, respectively, for cultured dendritic cells. CONCLUSIONS: P. lilacinum conidia are capable of infecting and destroying both macrophages and dendritic cells, clearly demonstrating the ability of this pathogenic fungus to invade human phagocytic cells.

Interaction of an opportunistic fungus Purpureocillium lilacinum with human macrophages and dendritic cells

Introduction Purpureocillium lilacinum is emerging as a causal agent of hyalohyphomycosis that is refractory to antifungal drugs; however, the pathogenic mechanisms underlying P. lilacinum infection are not understood. In this study, we investigated the interaction of P. lilacinum conidia with human macrophages and dendritic cells in vitro. Methods Spores of a P. lilacinum clinical isolate were obtained by chill-heat shock. Mononuclear cells were isolated from eight healthy individuals. Monocytes were separated by cold aggregation and differentiated into macrophages by incubation for 7 to 10 days at 37°C or into dendritic cells by the addition of the cytokines human granulocyte-macrophage colony stimulating factor and interleukin-4. Conidial suspension was added to the human cells at 1:1, 2:1, and 5:1 (conidia:cells) ratios for 1h, 6h, and 24h, and the infection was evaluated by Giemsa staining and light microscopy. Results After 1h interaction, P. lilacinum conidia were internalized by human cells and after 6h contact, some conidia became inflated. After 24h interaction, the conidia produced germ tubes and hyphae, leading to the disruption of macrophage and dendritic cell membranes. The infection rate analyzed after 6h incubation of P. lilacinum conidia with cells at 2:1 and 1:1 ratios was 76.5% and 25.5%, respectively, for macrophages and 54.3% and 19.5%, respectively, for cultured dendritic cells. Conclusions P. lilacinum conidia are capable of infecting and destroying both macrophages and dendritic cells, clearly demonstrating the ability of this pathogenic fungus to invade human phagocytic cells. .

Exploring N-acylhydrazone derivatives against clinical resistant bacterial strains.

Bacterial multiresistance is a health problem worldwide that demands new antimicrobials for treating bacterial-related infections. In this study, we evaluated the antimicrobial activity and the theoretical toxicology profile of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazide derivatives against gram-positive and gram-negative bacteria clinical strains. On that purpose we determined the minimum inhibitory (MIC) and bactericidal (MBC) concentrations, the in vitro cytotoxicity, and in silico risk profiles, also comparing with antimicrobial agents of clinical use. Among the 16 derivatives analyzed, four nitrofurans (N-H-FUR-NO(2), N-Br-FUR-NO(2), N-F-FUR-NO(2), N-Cl-FUR-NO(2)) showed promising MIC and MBC values (MIC = MBC = 1-16 µg/mL). The experimental data revealed the potential of these derivatives, which were comparable to the current antimicrobials with similar bactericidal and bacteriostatic profiles. Therefore, these molecules may be feasible options to be explored for treating infections caused by multiresistant strains. Our in vitro and in silico toxicity reinforced these results as these derivatives presented low cytotoxicity against human macrophages and low theoretical risk profile for irritant and reproductive effects compared to the current antimicrobials (e.g., vancomycin and ciprofloxacin). The molecular modeling analysis also revealed positive values for their theoretical druglikeness and drugscore. The presence of a 5-nitro-2-furfur-2-yl group seems to be essential for the antimicrobial activity, which pointed these acylhydrazone derivatives as promising for designing more potent and safer compounds.

New oxirane derivatives of 1,4-naphthoquinones and their evaluation against T. cruzi epimastigote forms.

New oxirane derivatives were synthesized using six naphthoquinones as the starting materials. Our biological results showed that these oxiranes acted as trypanocidal agents against Trypanosoma cruzi with minimal cytotoxicity in the VERO cell line compared to naphthoquinones. In particular, oxirane derivative 14 showed low cytotoxicity in a mammalian cell line and exhibited better activity against epimastigote forms of T.cruzi than the current drug used to treat Chagas disease, benznidazole.

Avaliação da atividade antimicrobiana do MTA ecimento portland em cepas de enterococcus faecalise pseudomonas aeruginosa / Evaluation of antimicrobial activity of MTA and Portland cements in enterococcus faecalis and pseudômonas aeruginosa

A determinação do perfil antimicrobiano de materiais endodônticos é de grande importância para determinação dos procedimentosodontológicos. O objetivo do presente trabalho foi avaliar o perfil antimicrobiano dos cimentos endodônticos MTA, que vem constituindo-se um excelente selador e preenchedor especialmente nas perfurações radiculares e de furca e que até então possuíam um prognóstico bastante desfavorável, e o Cimento Portland, que vem sendo utilizado com eficácia no tratamento da polpa dentária, frente a cepas de Enterococcusfaecalis e Pseudomonasaeruginosa, bactérias comumente resistentes aos antimicrobianos atuais e encontradas na maioria dos casos de lesões endodônticas refratárias. No teste antimicrobiano, os cimentos foram diluídos em água destilada e aplicados em discos de papel de filtro estéreis que foram colocados em placas de Petri inoculadas com as bactérias. O teste estatístico utilizado (ANOVA) permitiu inferir que houve uma diferença significante (p<0,05) entre os controles positivos e os cimentos avaliados. Com base nos resultados obtidos, pode se concluir que nenhum dos cimentos testados, MTA ou Portland, apresentam atividade antimicrobiana sobre as cepas testadas exigindo, portanto um protocolo de desinfecção prévio ao se utilizar esses materiais na prática odontológica.

The determination of the antimicrobial profile of endodontic materials are of great importance for the dental procedures establishment.The aim of this study was to evaluate the profile of antimicrobial sealers MTA, which is an excellent sealer and filler especially in the root and furcation perforations, which had unfavorable prognosis and Portland cement, which has been used efectivelly in dental pulp treatment against Enterococcus faecalis and Pseudomonas aeruginosathat are the resistant bacteria present in most cases of refractory endodontic infections. In the antimicrobial test, the material was diluted in distilled water and applied on filter paper discs that were placed in Petri dishes inoculated with bacteria. The ANOVA statistical test allowed us to infer that there was a statistically significant difference with p <0.05 when comparing positive controls, and cements. After theexperiments, we can conclude that none of the sealers, MTA or Portland, showed antimicrobial activity against the strains tested, thus requiring a protocol for disinfection prior to using these materials.

Evaluation of Leishmania (Leishmania) chagasi strains isolated from dogs originating from two visceral leishmaniasis-endemic areas in Brazil using multilocus enzyme electrophoresis / Avaliação de amostras de Leishmania (Leishmania) chagasi isoladas de cães oriundos de duas áreas endêmicas de leishmaniose visceral no Brasil através da eletroforese de isoenzimas

INTRODUCTION: Domestic dogs are the most important reservoir in the peridomestic transmission cycle of Leishmania (Leishmania) chagasi. The genetic variability of subpopulations of this parasite circulating in dogs has not been thoroughly analyzed in Brazil, even though this knowledge has important implications in the clinical-epidemiological context. METHODS: The objective of this study was to evaluate and compare the phenotypic variability of 153 L. chagasi strains isolated from dogs originating from the municipalities of Rio de Janeiro (n = 57) and Belo Horizonte (n = 96), where the disease is endemic. Strains isolated only from intact skin were selected and analyzed by multilocus enzyme electrophoresis using nine enzyme systems (6PG, GPI, NH1 and NH2, G6P, PGM, MDH, ME, and IDHNADP). RESULTS: The electrophoretic profile was identical for all isolates analyzed and was the same as that of the L. chagasi reference strain (MHOM/BR/74/PP75). Phenetic analysis showed a similarity index of one for all strains, with the isolates sharing 100 percent of the characteristics analyzed. CONCLUSIONS: The results demonstrate that the L. chagasi populations circulating in dogs from Rio de Janeiro and Belo Horizonte belong to a single zymodeme.

INTRODUÇÃO: Cães domésticos são considerados os reservatórios mais importantes no ciclo peridoméstico de transmissão de Leishmania (Leishmania) chagasi. No entanto, a variabilidade genética de sub-populações que circulam neste hospedeiro é ainda pouco explorada no Brasil, sendo tal conhecimento de grande importância no contexto clínico-epidemiológico. MÉTODOS: O objetivo deste estudo foi avaliar e comparar a variabilidade fenotípica de 153 amostras de L. chagasi isoladas de cães oriundos dos municípios do Rio de Janeiro (n = 57) e Belo Horizonte (n = 96), onde a doença é endêmica. Foram selecionadas somente amostras isoladas de pele íntegra e analisadas por eletroforese de isoenzimas (MLEE) empregando nove sistemas enzimáticos (6PG, GPI, NH1 e NH2, G6P, PGM, MDH, ME, IDHNADP). RESULTADOS: Todas as amostras analisadas apresentaram perfil eletroforético idêntico entre si e com a amostra de L. chagasi utilizada como referência neste estudo (MHOM/BR/74/PP75). A análise fenética demonstrou índice de similaridade igual a um para todas as amostras, revelando um compartilhamento de 100 por cento dos caracteres avaliados. CONCLUSÕES: A partir desses resultados, podemos inferir que as populações de L. chagasi que estão circulando nos cães do Rio de Janeiro e Belo Horizonte podem ser agrupadas em um único zimodema.

Evaluation of Leishmania (Leishmania) chagasi strains isolated from dogs originating from two visceral leishmaniasis-endemic areas in Brazil using multilocus enzyme electrophoresis.

INTRODUCTION: Domestic dogs are the most important reservoir in the peridomestic transmission cycle of Leishmania (Leishmania) chagasi. The genetic variability of subpopulations of this parasite circulating in dogs has not been thoroughly analyzed in Brazil, even though this knowledge has important implications in the clinical-epidemiological context. METHODS: The objective of this study was to evaluate and compare the phenotypic variability of 153 L. chagasi strains isolated from dogs originating from the municipalities of Rio de Janeiro (n = 57) and Belo Horizonte (n = 96), where the disease is endemic. Strains isolated only from intact skin were selected and analyzed by multilocus enzyme electrophoresis using nine enzyme systems (6PG, GPI, NH1 and NH2, G6P, PGM, MDH, ME, and IDHNADP). RESULTS: The electrophoretic profile was identical for all isolates analyzed and was the same as that of the L. chagasi reference strain (MHOM/BR/74/PP75). Phenetic analysis showed a similarity index of one for all strains, with the isolates sharing 100% of the characteristics analyzed. CONCLUSIONS: The results demonstrate that the L. chagasi populations circulating in dogs from Rio de Janeiro and Belo Horizonte belong to a single zymodeme.

Comparative analysis of viperidae venoms antibacterial profile: a short communication for proteomics.

Bacterial infections involving multidrug-resistant strains are one of the ten leading causes of death and an important health problem in need for new antibacterial sources and agents. Herein, we tested and compared four snake venoms (Agkistrodon rhodostoma, Bothrops jararaca, B. atrox and Lachesis muta) against 10 Gram-positive and Gram-negative drug-resistant clinical bacteria strains to identify them as new sources of potential antibacterial molecules. Our data revealed that, as efficient as some antibiotics currently on the market (minimal inhibitory concentration (MIC) = 1-32 µg mL(-1)), A. rhodostoma and B. atrox venoms were active against Staphylococcus epidermidis and Enterococcus faecalis (MIC = 4.5 µg mL(-1)), while B. jararaca inhibited S. aureus growth (MIC = 13 µg ml(-1)). As genomic and proteomic technologies are improving and developing rapidly, our results suggested that A. rhodostoma, B. atrox and B. jararaca venoms and glands are feasible sources for searching antimicrobial prototypes for future design new antibiotics against drug-resistant clinical bacteria. They also point to an additional perspective to fully identify the pharmacological potential of these venoms by using different techniques.

Trypanosoma cruzi: insights into naphthoquinone effects on growth and proteinase activity.

In this study we compared the effects of naphthoquinones (α-lapachone, ß-lapachone, nor-ß-lapachone and Epoxy-α-lap) on growth of Trypanosoma cruzi epimastigotes forms, and on viability of VERO cells. In addition we also experimentally analyzed the most active compounds inhibitory profile against T. cruzi serine- and cysteine-proteinases activity and theoretically evaluated them against cruzain, the major T. cruzi cysteine proteinase by using a molecular docking approach. Our results confirmed ß-lapachone and Epoxy-α-lap with a high trypanocidal activity in contrast to α-lapachone and nor-ß-lapachone whereas Epoxy-α-lap presented the safest toxicity profile against VERO cells. Interestingly the evaluation of the active compounds effects against T. cruzi cysteine- and serine-proteinases activities revealed different targets for these molecules. ß-Lapachone is able to inhibit the cysteine-proteinase activity of T. cruzi proteic whole extract and of cruzain, similar to E-64, a classical cysteine-proteinase inhibitor. Differently, Epoxy-α-lap inhibited the T. cruzi serine-proteinase activity, similar to PMSF, a classical serine-proteinase inhibitor. In agreement to these biological profiles in the enzymatic assays, our theoretical analysis showed that E-64 and ß-lapachone interact with the cruzain specific S2 pocket and active site whereas Epoxy-α-lap showed no important interactions. Overall, our results infer that ß-lapachone and Epoxy-α-lap compounds may inhibit T. cruzi epimastigotes growth by affecting T. cruzi different proteinases. Thus the present data shows the potential of these compounds as prototype of protease inhibitors on drug design studies for developing new antichagasic compounds.

Antiophidian sera sterility control: topics in perspective / Controle de esterilidade de soros antiofídicos: temas em perspectiva

The aim of this work is to review the most important topics about the antiophidic sera sterility, including obtaining methods, sterilization procedures and clean room control using Vital Brazil Institute (VBI) as an example. Bibliographical research was performed through Medline, Lilacs, PubMed, ISI and the Fundação Oswaldo Cruz - RJ and VBI Libraries, from 1960 to 2009. The antiophidic sera for human use are immunobiologic products produced in Brazil by three national laboratories, including VBI. Due to the parenteral use, these products should be sterile and pyrogen-free, which demands the microbiological control during the whole fabrication process. The sterility and pyrogen tests are important steps to ensure the quality and safety of these immunobiological products. Thus, these tests are target for continue evaluation and improvement. The most interfering aspects in the consistency and analytical patterns include the proper method selection, sampling, culture conditions and validation criteria. As the national and international legal requirements are cautious with the assays validation and approval of sterile parenteral products; the intrinsic limitations for established assays still require more investigation aiming the continue improvement of the microorganism and contaminants detection methods and optimization of the analysis extent.

O objetivo deste trabalho é revisar os tópicos mais relevantes para o controle da esterilidade de soros antiofídicos, abordando-se métodos de obtenção, procedimentos de esterilização e o controle de áreas limpas utilizando como exemplo os procedimentos adotados pelo Instituto Vital Brazil (IVB). Um levantamento bibliográfico foi realizado no Medline, ISI, Biblioteca da Fundação Oswaldo Cruz-RJ e IVB, no período de 1960 a 2009. Os soros antiofídicos para uso humano são produtos imunobiológicos fabricados no Brasil por três laboratórios nacionais, dentre eles o IVB. Por serem de administração parenteral, devem ser obrigatoriamente estéreis e apirogênicos, exigindo controle microbiológico durante todo o processo de fabricação. O teste de esterilidade e apirogenia são importantes instrumentos para garantir a qualidade e segurança microbiológica desses produtos, sendo alvo de avaliações constantes para seus aprimoramentos. Os aspectos que mais interferem na sua consistência e valor analítico incluem a escolha adequada do método, amostragem, condições de cultivo e critérios de validação. À medida que os requisitos legais nacionais e internacionais se mostram rigorosos na validação de ensaios e aprovação de produtos estéreis parenterais, limitações intrínsecas ao ensaio padronizado requisitam mais investigações, objetivando o aprimoramento contínuo nos métodos de detecção de microorganisms, contaminantes e otimização do tempo total de análise.

Leishmania amazonensis growth inhibitors: biological and theoretical features of sulfonamide 4-methoxychalcone derivatives.

Current drugs for treating leishmaniasis are still associated with significant toxicity and failure rates. Thus, new effective and less toxic antileishmanial agents are still in need. Herein, we tested a series of sulfonamide 4-methoxychalcone derivatives against L. amazonensis promastigote and amastigote forms to identify its antileishmanial profile against this species compared to L. braziliensis. In addition, we used molecular modeling tools to determine stereoelectronic features that may lead to the antileishmanial profile. Interestingly, all tested compounds were able to affect L. amazonensis promastigote form in a concentration-dependent manner and with low cytotoxicity, except for derivative 3g. However, our results showed that compound 3f (para-Cl) presents the best profile against both L. amazonensis forms (promastigote and amastigote), differently from that observed for L. braziliensis, when compound 3i was the most active. Structure-activity relationship (SAR) analysis of these derivatives pointed molecular volume, HOMO density, and conformational aspects as important characteristics for parasitic profile. Overall, sulfonamide 4-methoxychalcone derivatives may be pointed out not only as lead compounds for treating leishmaniasis (i.e., 3f) but also as experimental tools presenting parasite-selectivity (i.e., 3i).

Antibacterial profile against drug-resistant Staphylococcus epidermidis clinical strain and structure-activity relationship studies of 1H-pyrazolo[3,4-b]pyridine and thieno[2,3-b]pyridine derivatives.

Antibacterial resistance is a complex problem that contributes to health and economic losses worldwide. The Staphylococcus epidermidis is an important nosocomial pathogen that affects immunocompromised patients or those with indwelling devices. Currently, there are several resistant strains including S. epidermidis that became an important medical issue mainly in hospital environment. In this work, we report the biological and theoretical evaluations of a 4-(arylamino)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acids series (1, 1a-m) and the comparison with a new isosteric ring nucleus series, 4-(arylamino)thieno[2,3-b]pyridine-5-carboxylic acids derivatives (2, 2a-m). Our results revealed the 1H-pyrazolo[3,4-b]pyridine derivatives significant antibacterial activity against a drug-resistant S. epidermidis clinical strain in contrast to the thieno[2,3-b]pyridine series. The minimal inhibitory concentration (MIC) of the most active derivatives (1a, 1c, 1e, and 1f) against S. epidermidis was similar to that of oxacillin and twofold better than chloramphenicol. Interestingly, the position of the functional groups has a great impact on the activity as observed in our structure-activity relationship (SAR) study. The SAR of 1H-pyrazolo[3,4-b]pyridine derivatives shows that the highest inhibitory activity is observed when the meta position is occupied by electronegative substituents. The molecular modeling analysis of frontier molecular orbitals revealed that the LUMO density is less intense in meta than in ortho and para positions for both series (1 and 2), whereas HOMO density is overconcentrated in 1H-pyrazolo[3,4-b]pyridine ring nucleus compared to the thieno[2,3-b]pyridine system. The most active derivatives of series 1 were submitted to in silico ADMET screening, which confirmed these compounds as potential antibacterial candidates.

DNA methylation: a promising target for the twenty-first century.

BACKGROUND: Over the last few years DNA methylation and its involvement in diseases such as cancer has become of great interest for applied research. Since reversal of aberrant DNA methylation may influence the behavior of tumors, the methylation of DNA CpG sites is a potential target for the development of inhibitors for use in cancer treatment. OBJECTIVE/METHODS: We briefly review the structural and mechanistic features of DNA methylation, including a structural analysis of the three main human DNA methyltransferases and some (pre)clinical results. RESULTS/CONCLUSION: Despite side effects, data obtained to date still support the vision that DNA-methylation, possibly associated with the use of histone deacetylases (HDACs) and/or artificial transcription factors (ATFs), is a promising target for improving anticancer therapy in the 21st century.

Ambiente virtual: ainda uma proposta para o ensino / Teaching and learning environments: still a proposition

O ambiente virtual de ensino e aprendizado envolve uma grande variedade de recursos educacionais que estão fundamentados na utilização de computadores e programas bem como no treinamento de profissionais. As principais críticas ao modelo virtual de ensino se referem à ausência da interação humana face-a-face e a falta de programas que invistam na preparação dos educadores para usar as ferramentas computacionais, acompanhando o avanço da tecnologia. Este trabalho mostra uma visão geral sobre a estruturação destes ambientes virtuais e sua utilização no ensino da química. Um estudo sobre o perfil computacional de 15 escolas e 16 professores que lecionam para um público infanto-juvenil de 3.253 estudantes no estado do Rio de Janeiro também foi realizado. A despeito dos problemas, o ensino virtual ainda pode ser utilizado como uma ferramenta para proporcionar o aprendizado a um número significativo de pessoas pertencentes ou não ao sistema educacional tradicional.

Leishmaniasis treatment--a challenge that remains: a review.

Leishmaniasis is a disease caused by flagellate protozoan Leishmania spp. and represents an emergent illness with high morbidity and mortality in the tropics and subtropics. Since the discovery of the first drugs for Leishmaniasis treatment (i.e., pentavalent antimonials), until the current days, the search for substances with antileishmanial activity, without toxic effects, and able to overcome the emergence of drug resistant strains still remains as the current goal. This article reports the development of new chemotherapies through the rational design of new drugs, the use of products derived from microorganisms and plants, and treatments related to immunity as new alternatives for the chemotherapy of leishmaniasis.

Just working with the cellular machine: A high school game for teaching molecular biology.

Molecular biology is a difficult comprehension subject due to its high complexity, thus requiring new teaching approaches. Herein, we developed an interdisciplinary board game involving the human immune system response against a bacterial infection for teaching molecular biology at high school. Initially, we created a database with several questions and a game story that invites the students for helping the human immunological system to produce antibodies (IgG) and fight back a pathogenic bacterium second-time invasion. The game involves answering questions completing the game board in which the antibodies "are synthesized" through the molecular biology process. At the end, a problem-based learning approach is used, and a last question is raised about proteins. Biology teachers and high school students evaluated the game and considered it an easy and interesting tool for teaching the theme. An increase of about 5-30% in answering molecular biology questions revealed that the game improves learning and induced a more engaged and proactive learning profile in the high school students.

Staphylococcus aureus: visitando uma cepa de importância hospitalar / Staphylococcus aureus: visiting a strain of clinical importance

O Staphylococcus aureus é uma bactéria do grupo dos cocos gram-positivos que faz parte da microbiota humana, mas que pode provocar doenças que vão desde uma infecção simples, como espinhas e furúnculos, até as mais graves, como pneumonia, meningite, endocardite, síndrome do choque tóxico e septicemia, entre outras. Essa bactéria foi uma das primeiras a serem controladas com a descoberta dos antibióticos, mas, devido a sua enorme capacidade de adaptação e resistência, tornou-se uma das espécies de maior importância no quadro das infecções hospitalares e comunitárias. Neste artigo faremos uma revisão sobre esse agente infeccioso e as bases dos mecanismos das patologias por ele provocadas, de forma a ressaltar a necessidade de mantê-lo como alvo para o desenho de novos antibióticos.

Staphylococcus aureus is a bacterium from Gram-positive coccus group, which is part of the human microbiota. It may cause diseases that may vary from simple infections (i.e., pimples and furuncles) to severe infections, such as pneumonia, meningitis, endocarditis, toxic shock syndrome and septicemia, among others. This bacterium was one of the first bacteria affected by antibacterial agents, however, its ability of adaptation and resistance turns it into an important hospital and communitarian pathogenic species of great concern. In this article we will discuss some important points related to the S. aureus and the pathologies related to it to reinforce it as a target for the design of new antibiotics.

Plaquetas: ainda um alvo terapêutico / Platelets: still a therapeutical target

As plaquetas são fragmentos citoplasmáticos anucleados presentes no sangue e produzidos na medula óssea a partir dos megacariócitos. O objetivo deste trabalho é rever as bases mecanísticas e moleculares das plaquetas, revelando sua participação em síndromes importantes e na trombose arterial, além de seu potencial como alvo terapêutico para o desenho de novos agentes antitrombóticos.

Platelets are cytoplasmatic fragments from bone marrow megakaryocytes present on blood. The aim of this work is to review the basis of platelet mechanisms, their participation in syndromes and in arterial thrombosis, and its potential as a target for design of antithrombotic agents.