EP80317 Restrains Inflammation and Mortality Caused by Scorpion Envenomation in Mice

Over 1 million cases of scorpion stings are estimated every year, whereas current treatment is limited to antivenom serum combined with supportive therapy. Tityus serrulatus scorpion venom (TsV) is composed of diverse molecules, including toxins that induce a catecholamine storm and mediate classical symptoms of scorpion envenomation. However, the same toxins promote an intense inflammatory response coordinated by innate immune cells, such as macrophages, contributing significantly to the lung edema and mortality caused by TsV injection. Macrophages sense TsV via innate immune receptors, including TLR2, TLR4, and CD14 that promote inflammation and mortality via PGE2/cAMP/PKA/NF-κB/IL-1β axis. The scavenger receptor CD36 also recognizes TsV, but in contrast to the other receptors, it drives the production of leukotriene B4 (LTB4). This lipid mediator operates via BLT1 receptor to reduce cAMP production and consequently IL-1β release, which results in resistance to fatal outcomes of experimental scorpion envenomation. EP80317 is an hexapeptide that serves as a ligand for CD36 and features protective effects under conditions such as atherosclerosis and vascular inflammation. In this study, we evaluated the effects of EP80317 treatment during experimental scorpion envenomation. EP80317 treatment suppressed mouse peritoneal macrophage production of IL-1β, IL-6, tumor necrosis factor (TNF-α), CCL3, and PGE2in vitro. EP80317 treatment also boosted the production of LTB4 and IL-10 in response to TsV. Importantly, EP80317 restrained lung inflammation and mortality caused by TsV in vivo. Taken together, these data indicate a strong therapeutic potential of EP80317 as a supportive treatment to control inflammation induced by scorpion envenomation

Vacinas: importância, verdades e mitos – uma revisão bibliográfica

Introduction: Since its implementation, the vaccination process has been questioning and criticizing its effectiveness, immunological functioning and results. From this, even though it is an efficient public policy in the fight against infectious diseases, we are aware of the non-achievement, which harms the prevention of disease morbidity and mortality. Methods: Bibliographical review using as databases the Google academic, Medline, Center for Biotechnology Information (PubMed) and the electronic library Scientific Electronic Library Online (SciELO). The search was carried out of articles published between 2008 and 2018, in Portuguese and / or English. Development: The efficacy of the vaccine is based on the immune response of the host against an antigen can induce a memory T cell response over time. There are several reports of cases of autoimmune diseases following vaccination, however, due to the limited number of cases, different classifications of the symptoms and the disease latency period, all attempts at anti-vaccination studies have so far failed to achieve a connection plausible. Conclusion: Therefore, the population should seek information from reliable sources and from government agencies. In addition, health professionals, education managers and the media should suggest an important strategy for maintaining vaccine coverage and addressing vaccine refusal ethically.Introdução: O processo de vacinação enfrenta, desde a sua implementação, questionamentos e críticas acerca de sua efetividade, funcionamento imunológico e resultados. À partir disso, mesmo sendo uma política pública eficiente no combate de doenças infectocontagiosas, tem-se a consciência da não realização da mesma, o que prejudica na prevenção da morbimortalidade das doenças infectocontagiosas. Métodos: Revisão bibliográfica utilizando como bases de dados o Google acadêmico, Medline, Center for Biotechnology Information (PubMed) e na biblioteca eletrônica Scientific Eletronic Library Online (SciELO). A busca foi realizada em artigos publicados no período de 2008 a 2018, em português e/ou inglês. Desenvolvimento: A eficácia da vacina baseia-se na resposta imune do hospedeiro contra um antígeno que possa induzir uma resposta da célula T de memória ao longo do tempo. Existem vários relatos de casos de doenças autoimunes após a vacinação; no entanto, devido ao número limitado de casos, as diferentes classificações dos sintomas e ao período de latência das doenças, todas as tentativas de estudos antivacinação, até o momento, não conseguiram uma correlação plausível. Conclusão: Portanto, a população deve buscar informações em fontes confiáveis e em órgãos governamentais. Além disso, profissionais da saúde, gestores da educação e a mídia devem sugerir estratégias importantes para manter as coberturas vacinais e abordar a recusa vacinal de forma ética

The anti-inflammatory and antitumor effects of medicinal plants: Arctium lappa, Solanum torvum and Lobelia inflata

Introduction: Medicinal plants have been used since antiquity to treat illnesses and injuries. Considering their global use, many natural products have been investigated with the aim to get new drugs. Methods: The search was based on relevant articles indexed in PubMed, Scielo and Scopus. The search terms used were: medicinal plants, Arctium lappa, Solanum torvum, Lobelia inflata, anti-inflammatory effects, antimicrobial activity and antitumor effects. Development: Arctium lappa leads to the inhibition of nitric oxide synthase (iNOS) expression and nitric oxide (NO) production and inhibits the growth of some tumor cell lines. Solanum torvum can promote inhibition of inflammatory mediators release, and reduces the melanoma formation. Lobelia inflata can reduce the number of white blood cells, the TNF-α and IL-6 levels and the melanoma growth. Conclusion: The active principles present in these medicinal plants, including flavonoids and other phenolic compounds with antioxidant activity, can scavenge free radicals and therefore be effective against tumors, such as melanoma and skin cancer

Partial purification and functional characterization of Ts19 Frag-I, a novel toxin from Tityus serrulatus scorpion venom

Abstract\ud \ud Background\ud The yellow scorpion Tityus serrulatus (Ts) is responsible for the highest number of accidents and the most severe scorpion envenoming in Brazil. Although its venom has been studied since the 1950s, it presents a number of orphan peptides that have not been studied so far. The objective of our research was to isolate and identify the components present in the fractions VIIIA and VIIIB of Ts venom, in order to search for a novel toxin. The major isolated toxins were further investigated for macrophage modulation.\ud \ud \ud Methods\ud The fractions VIIIA and VIIIB, obtained from Ts venom cation exchange chromatography, were rechromatographed on a C18 column (4.6 × 250 mm) followed by a reversed-phase chromatography using another C18 column (2.1 × 250 mm). The main eluted peaks were analyzed by MALDI-TOF and Edman’s degradation and tested on macrophages.\ud \ud \ud Results\ud The previously described toxins Ts2, Ts3-KS, Ts4, Ts8, Ts8 propeptide, Ts19 Frag-II and the novel peptide Ts19 Frag-I were isolated from the fractions VIIIA and VIIIB. Ts19 Frag-I, presenting 58 amino acid residues, a mass of 6,575 Da and a theoretical pI of 8.57, shares high sequence identity with potassium channel toxins (KTx). The toxins Ts4, Ts3-KS and the partially purified Ts19 Frag-I did not produce cytotoxic effects on macrophage murine cells line (J774.1). On the other hand, Ts19 Frag-I induced the release of nitric oxide (NO) by macrophages, while Ts4 and Ts3-KS did not affect the NO production at the tested concentration (50 μg/mL). At the same concentration, Ts19 Frag-I and Ts3-KS increased the production of interleukin-6 (IL-6). Ts19 Frag-I and Ts4 did not induce the release of IL-10, IL-1β or tumor necrosis factor-α by macrophage cells using the tested concentration (50 μg/mL).\ud \ud \ud Conclusions\ud We partially purified and determined the complete sequence and chemical/physical parameters of a new β-KTx, denominated Ts19 Frag-I. The toxins Ts4, Ts3-KS and Ts19 Frag-I showed no cytotoxicity toward macrophages and induced IL-6 release. Ts19 Frag-I also induced the release of NO, suggesting a pro-inflammatory activity.This study received financial support from the from the State of São Paulo\ud Research Foundation (FAPESP – scholarship to FAC n. 2012/13590-8 and\ud MBP n. 2012/12954-6), Coordination for the Improvement of Higher\ud Education Personnel (CAPES – scholarship to PCL), National Council for\ud Scientific and Technological Development (CNPq – grant n. 303689/2013-7)\ud and the Support Nucleus for Research on Animal Toxins (NAP-TOXAN-USP,\ud grant n. 12-125432.1.3). The authors would like to thank Prof. Dr. Norberto\ud Peporine Lopes for providing the MALDI-TOF mass spectrometer used in this\ud study. The authors also acknowledge the biologist Luiz Henrique Anzaloni Pedrosa\ud for extracting the scorpion venom and Iara Aimê Cardoso for technical assistance.\ud Thanks are also due to the Center for the Study of Venoms and Venomous\ud Animals (CEVAP) of UNESP for enabling the publication of this special collection\ud (CNPq process 469660/2014-7)

Monitoramento no âmbito hospitalar: avaliação da carga microbiana

Introduction: Hospital infections (HI) constitute a serious public health problem, which may occur during hospitalization or after discharge. It is undeniable that environmental contamination, involving important microorganisms (Staphylococcus aureus, Enterococcus, Acinetobacter spp., Clostridium difficile, among others) represents a risk of transmission between patients and professionals.. Objective: Given the importance of microbial control in HI prevention, the present study evaluated the microbial load of health professionals of a public hospital in the interior of the state of São Paulo, through the hand washing and dressing procedure, as well as the hospital environment. Methods: To perform the data collection, the Termo de Consentimento Livre e Esclarecido (TCLE) was applied. After the clarification of the TCLE, for the microbiological collections of the hands and clothes of the health professionals, laminous crops were used. And for the evaluation of the microbial load of the air, the sedimentation plate technique was used. Results: We observed the efficiency of the hand hygiene technique, since partial or total reduction of the microbial load occurred. As for clothing collections, the results are increasing numerically at the expense of the workday, in addition to presenting characteristics intrinsic to the activity developed by the professional. The results obtained through the sedimentation plates indicate that areas of lower flow of people and / or controlled access, such as beds, have a reduced total microbial load. Conclusion: The presence of microorganisms in the hospital environment is inevitable, however, prophylactic measures such as hand hygiene, and disinfection of surfaces and the correct use of clothes or periodic exchanges of the same contribute positively to the prevention of infections via the exogenous route.Introdução: As infecções hospitalares (IH) constituem um grave problema de saúde pública, podendo ocorrer durante o período de internação ou após a alta. É incontestável que a contaminação ambiental, envolvendo importantes microrganismos (Staphylococcus aureus, Enterococcus, Acinetobacter spp., Clostridium difficile entre outros) representa risco de transmissão entre pacientes e profissionais. Objetivo: Dado a importância do controle microbiano na prevenção de IH, o presente estudo avaliou a carga microbiana dos profissionais da saúde de um hospital público do interior do estado de São Paulo, através do procedimento de lavagem das mãos e das vestimentas, bem como do ambiente hospitalar. Métodos: Para realização das coletas foi aplicado o Termo de Consentimento Livre e Esclarecido (TCLE). Após o esclarecimento do TCLE, foram utilizados laminocultivos para as coletas microbiológicas das mãos e vestimentas dos profissionais da saúde. Para avaliação da carga microbiana do ar, foi utilizado a técnica da placa de sedimentação. Resultados: Nós observamos a eficiência da técnica de higienização das mãos, visto que ocorreu redução parcial ou total da carga microbiana. Já para as coletas das vestimentas, os resultados apresentam-se crescente numericamente em detrimento do decorrer da jornada de trabalho, além de apresentarem características intrínsecas à própria atividade desenvolvida pelo profissional. Os resultados obtidos através das placas de sedimentação indicam que áreas de menor fluxo de pessoas e/ou de acesso controlado, como os leitos, possuem a carga microbiana total reduzida. Conclusão: A presença de microrganismos no ambiente hospitalar é inevitável, entretanto, medidas profiláticas como a higienização das mãos, desinfecção de superfícies e a correta utilização das vestimentas ou troca periódica das mesmas contribuem positivamente na prevenção de infecções pela via exógena

Green Propolis Compounds (Baccharin and p-Coumaric Acid) Show Beneficial Effects in Mice for Melanoma Induced by B16f10

Background: Cutaneous melanoma is the most aggressive form of skin cancer, with the worst prognosis, and it affects a younger population than most cancers. The high metastatic index, in more advanced stages, and the high aggressiveness decrease the effectiveness of currently used therapies, such as surgical removal, radiotherapy, cryotherapy, and chemotherapy, used alone or in combination. Based on these disadvantages, research focused on alternative medicine offers great potential for therapeutic innovation. Medicinal plants represent a remarkable source of compounds for the treatment of various diseases. Methods: In this study, we investigated the tumoral behavior of melanoma under treatment with the compounds baccharin and p-coumaric acid, extracted from green propolis, in mice inoculated with B16F10 cells for 26 days. Results: A significant modulation in the number of inflammatory cells recruited to the tumor region and blood in the groups treated with the compounds was observed. In addition, a significant reduction in the amount of blood vessels and mitosis in the neoplastic area was noticed. Conclusions: Through our research, we confirmed that baccharin and coumaric acid, isolated substances from Brazilian green propolis, have a promising anticarcinogenic potential to be explored for the development of new antitumor agents, adhering to the trend of drugs with greater tolerance and biological effectiveness

CD36 Shunts Eicosanoid Metabolism to Repress CD14 Licensed Interleukin-1β Release and Inflammation

Interleukin (IL)-1β is a potential target for treatment of several inflammatory diseases, including envenomation by the scorpion Tityus serrulatus. In this context, bioactive lipids such as prostaglandin (PG)E2 and leukotriene (LT)B4 modulate the production of IL-1β by innate immune cells. Pattern recognition receptors (PRRs) that perceive T. serrulatus venom (TsV), and orchestrate LTB4, PGE2, and cyclic adenosine monophosphate (cAMP) production to regulate IL-1β release are unknown. Furthermore, molecular mechanisms driving human cell responses to TsV remain uncharacterized. Here, we identified that both CD14 and CD36 control the synthesis of bioactive lipids, inflammatory cytokines, and mortality mediated by TsV. CD14 induces PGE2/cAMP/IL-1β release and inflammation. By contrast, CD36 shunts eicosanoid metabolism toward production of LTB4, which represses the PGE2/cAMP/IL-1β axis and mortality. Of importance, the molecular mechanisms observed in mice strongly correlate with those of human cell responses to TsV. Overall, this study provides major insights into molecular mechanisms connecting CD14 and CD36 with differential eicosanoid metabolism and inflammation mediated by IL-1β