RESUMO
Sphingomyelinase D (SMase D), the main toxic component of Loxosceles venom, has a well-documented role on dermonecrotic lesion triggered by envenomation with these species; however, the intracellular mechanisms involved in this event are still poorly known. Through differential transcriptomics of human keratinocytes treated with L. laeta or L. intermedia SMases D, we identified 323 DEGs, common to both treatments, as well as upregulation of molecules involved in the IL-1 and ErbB signaling. Since these pathways are related to inflammation and wound healing, respectively, we investigated the relative expression of some molecules related to these pathways by RT-qPCR and observed different expression profiles over time. Although, after 24 h of treatment, both SMases D induced similar modulation of these pathways in keratinocytes, L. intermedia SMase D induced earlier modulation compared to L. laeta SMase D treatment. Positive expression correlations of the molecules involved in the IL-1 signaling were also observed after SMases D treatment, confirming their inflammatory action. In addition, we detected higher relative expression of the inhibitor of the ErbB signaling pathway, ERRFI1, and positive correlations between this molecule and pro-inflammatory mediators after SMases D treatment. Thus, herein, we describe the cell pathways related to the exacerbation of inflammation and to the failure of the wound healing, highlighting the contribution of the IL-1 signaling pathway and the ERRFI1 for the development of cutaneous loxoscelism.
Assuntos
Esfingomielina Fosfodiesterase , Venenos de Aranha , Animais , Humanos , Inflamação , Interleucina-1/metabolismo , Diester Fosfórico Hidrolases/toxicidade , Transdução de Sinais , Esfingomielina Fosfodiesterase/metabolismo , Aranhas/química , Aranhas/metabolismo , Venenos de Aranha/toxicidade , Picada de Aranha/patologia , Receptores ErbB/metabolismoRESUMO
Sphingomyelinase D (SMase D), the main toxic component of Loxosceles venom, has a well-documented role on dermonecrotic lesion triggered by envenomation with these species; however, the intracellular mechanisms involved in this event are still poorly known. Through differential transcriptomics of human keratinocytes treated with L. laeta or L. intermedia SMases D, we identified 323 DEGs, common to both treatments, as well as upregulation of molecules involved in the IL-1 and ErbB signaling. Since these pathways are related to inflammation and wound healing, respectively, we investigated the relative expression of some molecules related to these pathways by RT-qPCR and observed different expression profiles over time. Although, after 24 h of treatment, both SMases D induced similar modulation of these pathways in keratinocytes, L. intermedia SMase D induced earlier modulation compared to L. laeta SMase D treatment. Positive expression correlations of the molecules involved in the IL-1 signaling were also observed after SMases D treatment, confirming their inflammatory action. In addition, we detected higher relative expression of the inhibitor of the ErbB signaling pathway, ERRFI1, and positive correlations between this molecule and pro-inflammatory mediators after SMases D treatment. Thus, herein, we describe the cell pathways related to the exacerbation of inflammation and to the failure of the wound healing, highlighting the contribution of the IL-1 signaling pathway and the ERRFI1 for the development of cutaneous loxoscelism.
RESUMO
Introdução: Nos últimos anos, com o avanço tecnológico e da medicina, a sobrevida dos pacientes internados nas unidades de terapia intensiva (UTI) tem aumentado consideravelmente. No entanto, muitos desses pacientes permanecem imóveis e restritos ao leito causando diversas consequências deletérias associadas à imobilidade prolongada. Objetivo: Elucidar os efeitos sistêmicos da mobilização precoce em pacientes adultos internados na UTI. Métodos: Trata-se de uma revisão realizada nas bases de dados eletrônica: Pubmed, Scielo e Web of Science. Foram selecionados artigos indexados publicados entre o período de 2012 a 2017. Foram encontrados 9 estudos relevantes a essa revisão. Resultados: De forma geral, essa prática proporcionou aumento da força muscular, aumento da pressão inspiratória máxima, redução na produção de citocinas pró-inflamatórias e do estresse oxidativo, menor permanência na ventilação mecânica (VM), menor tempo de internação hospitalar e maior qualidade de vida. Conclusão: A fisioterapia torna-se essencial no desenvolvimento da mobilização precoce, contribuindo para a melhora da funcionalidade e da qualidade de vida do paciente tanto no meio hospitalar quanto pós-alta.
Introduction: In recent years, with advances in technology and medicine, the survival of patients admitted to intensive care units (ICU) has increased considerably. However, many of these patients remain immobile and restricted in the beds causing several deleterious consequences associated with prolonged immobility. Objective: To elucidate the systemic effects of early mobilization in adult patients hospitalized in the ICU. Methods: This is a review carried out in the electronic databases: PubMed, Scielo and Web of Science. We selected indexed articles between 2012 and 2017. We found 9 studies relevant to this review. Results: In general, this practice increased muscle strength, increased maximal inspiratory pressure, reduced production of proinflammatory cytokines and oxidative stress, shorter mechanical ventilation (MV), shorter hospital stay and higher quality of life. Conclusion: Physical therapy becomes essential in the development of early mobilization, contributing to improve the functionality and quality of life of the patient both in hospital and post-discharge.
RESUMO
The aim of this study was to evaluate the accuracy of invasive and non-invasive tests for diagnosis of visceral leishmaniasis (VL) in a large series of human immunodeficiency virus (HIV)-infected patients. In this delayed-type cross-sectional study, 113 HIV-infected symptomatic patients were evaluated by an adjudication committee after clinical follow-up to establish the presence or absence of VL as the target condition (reference test). The index tests were recombinant K39 antigen-based immunochromatographic test (rK39), indirect fluorescent antibody test (IFAT), prototype kit of direct agglutination test (DAT-LPC), and real-time polymerase chain reaction (qPCR) in peripheral blood. Compared with parasitological test and adjudication committee diagnosis or latent class model analyses, IFAT and rk39 dipstick test presented the lowest sensitivity. DAT-LPC exhibited good overall performance, and there was no statistical difference between DAT-LPC and qPCR diagnosis accuracy. Real-time PCR emerges as a less invasive alternative to parasitological examination for confirmation of cases not identified by DAT.
Assuntos
Testes de Aglutinação/métodos , Técnica Indireta de Fluorescência para Anticorpo/métodos , Leishmaniose Visceral/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adulto , Anticorpos Antiprotozoários/sangue , Coinfecção/diagnóstico , Coinfecção/parasitologia , Coinfecção/virologia , Estudos Transversais , DNA de Protozoário/isolamento & purificação , Feminino , Infecções por HIV/parasitologia , Humanos , Leishmania/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
This case report describes an atypical clinical presentation of visceral leishmaniasis affecting the digestive tract and causing malabsorption syndrome in a patient without recognized immunosuppressive condition. After appropriate treatment for the classical visceral form of the disease, diarrhea persisted as the main symptom and massive infection by Leishmania was detected by histopathology analysis of the duodenal mucosa. Schistosoma mansoni coinfection was also confirmed and treated without impact on diarrhea. New course of amphotericin B finally led to complete improvement of diarrhea. Atypical visceral leishmaniasis involving the gastrointestinal tract is well recognized in HIV coinfection but very rare in immunocompetent patients. The factors determining the control or evolution of the Leishmania infection have not been completely identified. This case stresses the importance of atypical symptoms and the unusual location of visceral leishmaniasis, not only in immunodepressed patients, and raises the possible influence of chronic infection by S. mansoni reducing the immune response to Leishmania.