Differential effects of antigens from L. braziliensis isolates from disseminated and cutaneous leishmaniasis on in vitro cytokine production

BACKGROUND: Disseminated leishmaniasis is an emerging infectious disease, mostly due to L. braziliensis, which has clinical and histopathological features distinct from cutaneous leishmaniasis. METHODS: In the current study we evaluated the in vitro production of the cytokines IFN-γ, TNF-α, IL-5 and IL-10 by peripheral blood mononuclear cells (PBMC) from 15 disseminated leishmaniasis and 24 cutaneous leishmaniasis patients upon stimulation with L. braziliensis antigens genotyped as disseminated leishmaniasis or cutaneous leishmaniasis isolates. RESULTS: Regardless of the source of L. braziliensis antigens, PBMC from cutaneous leishmaniasis patients produced significantly higher IFN-γ than PBMC from disseminated leishmaniasis patients. Levels of TNF-α by PBMC from cutaneous leishmaniasis patients were significantly higher than disseminated leishmaniasis patients only when stimulated by genotyped cutaneous leishmaniasis antigens. The levels of IL-5 and IL-10 production by PBMC were very low and similar in PBMCs from both disseminated leishmaniasis and cutaneous leishmaniasis patients. The immune response of each patient evaluated by the two L. braziliensis antigens was assessed in a paired analysis in which we showed that L. braziliensis genotyped as disseminated leishmaniasis isolate was more potent than L. braziliensis genotyped as cutaneous leishmaniasis isolate in triggering IFN-γ and TNF-α production in both diseases and IL-5 only in cutaneous leishmaniasis patients. CONCLUSION: This study provides evidence that antigens prepared from genotypically distinct strains of L. braziliensis induce different degrees of immune response. It also indicates that both parasite and host play a role in the outcome of L. braziliensis infection

Differential Regional Immune Response in Chagas Disease

Following infection, lymphocytes expand exponentially and differentiate into effector cells to control infection and coordinate the multiple effector arms of the immune response. Soon after this expansion, the majority of antigen-specific lymphocytes die, thus keeping homeostasis, and a small pool of memory cells develops, providing long-term immunity to subsequent reinfection. The extent of infection and rate of pathogen clearance are thought to determine both the magnitude of cell expansion and the homeostatic contraction to a stable number of memory cells. This straight correlation between the kinetics of T cell response and the dynamics of lymphoid tissue cell numbers is a constant feature in acute infections yielded by pathogens that are cleared during the course of response. However, the regional dynamics of the immune response mounted against pathogens that are able to establish a persistent infection remain poorly understood. Herein we discuss the differential lymphocyte dynamics in distinct central and peripheral lymphoid organs following acute infection by Trypanosoma cruzi, the causative agent of Chagas disease. While the thymus and mesenteric lymph nodes undergo a severe atrophy with massive lymphocyte depletion, the spleen and subcutaneous lymph nodes expand due to T and B cell activation/proliferation. These events are regulated by cytokines, as well as parasite-derived moieties. In this regard, identifying the molecular mechanisms underlying regional lymphocyte dynamics secondary to T. cruzi infection may hopefully contribute to the design of novel immune intervention strategies to control pathology in this infection

2019 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations : summary from the basic life support; advanced life support; pediatric life support; neonatal life support; education, implementation, and teams; and first aid task forces

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

Implementing a prevalence study of dementia and geriatric depression in Portugal: the 10-66 Dementia Research Group methodology

RESUMO - Introdução: A demência e a depressão têm um impacto social muito significativo. Em Portugal, escasseiam dados epidemiológicos em pessoas idosas na comunidade. Em países em desenvolvimento, o 10/66 Dementia Research Group (DRG) conduziu múltiplos estudos sobre a prevalência e a incidência destes quadros. Os protocolos de avaliação 10/66-DRG foram validados extensivamente nesses países, havendo vantagens potenciais na aplicação em regiões europeias com populações idosas de baixa escolaridade. Neste estudo, fundamentamos e descrevemos a implementação em Portugal da metodologia 10/66-DRG para estudo da prevalência da demência e da depressão geriátrica. Materiais e métodos: O trabalho de campo desenrola-se numa fase única, em áreas geográficas definidas, sendo avaliados detalhadamente e de forma sistemática todos os residentes de 65 anos ou mais. A informação é recolhida dos participantes e de informadores próximos (www.alz.co.uk/1066/). Resultados: Selecionámos e mapeámos uma área urbana (em Fernão Ferro) e outra rural (em Mora), definindo amostras finais de 702 e 779 pessoas, respetivamente. Os instrumentos de avaliação foram cuidadosamente traduzidos e adaptados ao contexto português. Teve lugar um treino rigoroso dos entrevistadores, assegurando a fiabilidade de cotação interobservadores. Discussão e conclusão: A aplicação dos protocolos 10/66-DRG permitirá obter dados robustos de prevalência de demência e de depressão, com amostras comunitárias de pessoas idosas em Portugal. Dada a validade internacional da metodologia utilizada, estes resultados serão comparáveis com os de outros centros 10/66, à escala mundial.ABSTRACT - Introduction: Dementia and depression have a huge social impact. In Portugal, epidemiological data is scarce regarding community dwelling elderly people with these conditions. In developing countries, the 10/66 Dementia Research Group-DRG has conducted multiple studies on the corresponding prevalence and incidence. The 10/66-DRG protocols for population- -based studies were extensively validated in those countries, and there is a rationale to apply them in low literacy elderly populations in Europe. We describe the implementation of the protocols related to the prevalence study (on dementia and geriatric depression) in Portuguese settings. Materials and methods: This is a one-phase survey, in which all people 65+ years living in defined catchment areas are comprehensively evaluated. Information is collected directly from participants and from a related informant (www.alz.co.uk/1066/). Results: We selected and mapped an urban area (in Fernão Ferro) and a rural one (in Mora). The final samples were n = 702 and n = 779 respectively. Questionnaires were carefully translated and culturally adapted. Rigorous training procedures took place to ensure inter-rater reliability. Discussion and conclusions: The implementation of the 10/66-DRG protocols will lead to robust data on the prevalence of dementia and depression in community samples of elderly people in Portugal. Given the international validity of our methodology, these results will be comparable with those from other 10/66 centres around the world.info:eu-repo/semantics/publishedVersio

Direct targeting of hippocampal neurons for apoptosis by glucocorticoids is reversible by mineralocorticoid receptor activation

Prova tipográfica (In Press)An important question arising from previous observations in vivo is whether glucocorticoids can directly influence neuronal survival in the hippocampus. To this end, a primary postnatal hippocampal culture system containing mature neurons and expressing both glucocorticoid (GR) and mineralocorticoid (MR) receptors was developed. Results show that the GR agonist dexamethasone (DEX) targets neurons (microtubule-associated protein 2-positive cells) for death through apoptosis. GR-mediated cell death was counteracted by the MR agonist aldosterone (ALDO). Antagonism of MR with spironolactone ([7a-(acetylthio)-3-oxo-17a-pregn- 4-ene,21 carbolactone] (SPIRO)) causes a dose-dependent increase in neuronal apoptosis in the absence of DEX, indicating that nanomolar levels of corticosterone present in the culture medium, which are sufficient to activate MR, can mask the apoptotic response to DEX. Indeed, both SPIRO and another MR antagonist, oxprenoate potassium ((7a,17a)-17-Hydroxy-3-oxo-7- propylpregn-4-ene-21-carboxylic acid, potassium salt (RU28318)), accentuated DEX-induced apoptosis. These results demonstrate that GRs can act directly to induce hippocampal neuronal death and that demonstration of their full apoptotic potency depends on abolition of survival-promoting actions mediated by MR