Augmented plasma microparticles during acute Plasmodium vivax infection

Background: In the last few years, the study of microparticles (MPs) - submicron vesicles released from cells upon activation or apoptosis - has gained growing interest in the field of inflammation and in infectious diseases. Their role in the human malaria parasite Plasmodium vivax remains unexplored. Because acute vivax malaria has been related to pro-inflammatory responses, the main hypothesis investigated in this study was that Plasmodium vivax infection is associated with elevated levels of circulating MPs, which may play a role during acute disease in nonimmune patients. Methods: Plasma MPs were analysed among thirty-seven uncomplicated P. vivax infections from an area of unstable malaria transmission in the Brazilian Amazon. The MP phenotype was analysed by flow cytometry using the classical MP marker, annexin, and fluorochrome-labeled monoclonal antibodies against specific cell surface markers. The frequencies of plasma MPs in P. vivax patients (n = 37) were further compared to malaria-unexposed controls (n = 15) and ovarian carcinoma patients (n = 12), a known MPs-inducing disease non-related to malaria. Results: The frequencies of plasma circulating MPs were markedly increased in P. vivax patients, as compared to healthy age-matched malaria-unexposed controls. Although platelets, erythrocytes and leukocytes were the main cellular sources of MPs during vivax malaria, platelet derived-MPs (PMPs) increased in a linear fashion with the presence of fever at the time of blood collection (b = 0.06, p < 0.0001) and length of acute symptoms (b = 0.36, p < 0.0001). Finally, the results suggest that plasma levels of PMPs diminish as patient experience more episodes of clinical malaria (b = 0.07, p < 0.003). Conclusions: Abundant circulating MPs are present during acute P. vivax infection, and platelet derived-MPs may play a role on the acute inflammatory symptoms of malaria vivax

Increase of reactive oxygen species by desferrioxamine during experimental Chagas' disease.

Oxidative stress is common in inflammatory processes associated with many diseases including Chagas' disease. The aim of the present study was to evaluate, in a murine model, biomarkers of oxidative stress together with components of the antioxidant system in order to provide an overview of the mechanism of action of the iron chelator desferrioxamine (DFO). The study population comprised 48 male Swiss mice, half of which were treated daily by intraperitoneal injection of DFO over a 35-day period, while half were administered sterile water in a similar manner. On the 14th day of the experiment, 12 DFO-treated mice and an equal number of untreated mice were experimentally infected with Trypanosoma cruzi. Serum concentrations of nitric oxide and superoxide dismutase and hepatic levels of total glutathione, thiobarbituric acid reactive species and protein carbonyl, were determined on days 0, 7, 14 and 21 post-infection. The results obtained revealed that DFO enhances antioxidant activity in the host but also increases oxidative stress, indicating that the mode of action of the drug involves a positive contribution to the host together with an effect that is not beneficial to the parasite

Phytochemical screening and toxicity of Crambe abyssinica Hochst extracts on Solanum lycopersicum L., Euphorbia heterophylla L., Bidens pilosa L. and Glycine max (L.) Merril

This study aimed to identify the main groups of secondary compounds from Crambe abyssinica and evaluate the bioactivity of the hexane, ethyl acetate and methanol extracts on the seed germination and seedling development of tomato, wild poinsettia, hairy beggartick and soybean. The phytochemical screening considered the presence or absence of total saponins, triterpenoids, flavonoids, coumarins, tannins, phenols and alkaloids. In the seeds it was evaluated: germination percentage, germination velocity index, average germination time, index of allelopathic effects, shoot and root length and seedlings dry matter. In the phytochemical screening it was observed that each solvent extracted different compounds. Flavonoids were found only in the ethyl acetate extract and saponin only in the methanol extract. A high allelopathic effect of hexane, ethyl acetate and methanolic extracts of crambe on the bio-indicator species tomato was observed. The hexane and ethyl acetate extracts also showed inhibitory effect on the weed hairy beggartick and did not present negative effects on soybean. There is the possibility of isolating the bio-active compounds of crambe and use them as a bio-herbicide to the alternative control of the weed hairy beggartick

Trypanosoma cruzi: desferrioxamine decreases mortality and parasitemia in infected mice through a trypanostatic effect.

Desferrioxamine (DFO) is a potent iron chelator that is also known to modulate inflammation and act as an efficient antioxidant under normal conditions and under oxidative stress. Many in vitro and in vivo studies have shown the efficacy of DFO in the treatment of viral, bacterial and protozoan infections. DFO is known to reduce the intensity of Trypanosoma cruzi infections in mice even during a course of therapy that is not effective in maintaining anaemia or low iron levels. To further clarify these findings, we investigated the action of DFO on mouse T. cruzi infection outcomes and the direct impact of DFO on parasites. Infected animals treated with DFO (5 mg/animal/day) for 35 days, beginning 14 days prior to infection, presented lower parasitemia and lower cumulative mortality rate. No significant effect was observed on iron metabolism markers, erythrograms, leukograms or lymphocyte subsets. In the rapid method for testing in vivo T. cruzi susceptibility, DFO also induced lower parasitemia. In regard to its direct impact on parasites, DFO slightly inhibited the growth of amastigotes and trypomastigotes in fibroblast culture. Trypan blue staining showed no effects of DFO on parasite viability, and only minor apoptosis in trypomastigotes was observed. Nevertheless, a clear decrease in parasite mobility was detected. In conclusion, the beneficial actions of DFO on mice T. cruzi infection seem to be independent of host iron metabolism and free of significant haematological side effects. Through direct action on the parasite, DFO has more effective trypanostatic than trypanocidal properties

Inflammatory markers and occurrence of falls: Bambuí Cohort Study of Aging

OBJECTIVE: Analyze whether inflammatory markers are associated with falls among older adults living in Bambuí. METHODS: Study that analyzed baseline data from a Bambuí Cohort Study of Aging, involving 1,250 participants. Data about falls were collected from previous 12 months, classified as single or multiple occurrence and severity (participant seeking health services). Information about sociodemographic characteristics, health behaviors and health condition was also collected and used as confounding factors. The exposures of interest included interleukins (IL-1β, IL-6, IL-8, IL-10, IL-12), tumor necrosis factor (TNF), ultra-sensitive C-reactive protein (us-CRP) and chemokines (CXCL9, CCL5, CCL10, MCP1). Data were processed through logistic regression, obtaining odds ratio and 95% confidence interval (95%CI). RESULTS: The prevalence of falls was 27.1%; 40.1% of the older adults reported multiple falls and 33.3% sought health services. After adjustments, the following elevated levels were associated with falls: us-CRP (OR = 1.46, 95%CI 1.04–2.03), CCL5 (OR = 1.38, 95%CI 1.01–1.90) and CXCL9 (OR = 1.43, 95%CI 1.02–2.02). An association was observed between the number of elevated markers and the occurrence of falls: two (OR = 1.47, 95%CI 1.02–2.12) and three (OR = 2.08, 95%CI 1.12–3.87) elevated biomarkers indicated fall probability of 32.0% and 39.4%, respectively. CONCLUSIONS: Elevated levels of us-CRP, CCL5 and CXCL9, which were associated with falls, may contribute to a proper understanding of the mechanism associated with the occurrence of falls among older people.OBJETIVO: Analisar se marcadores inflamatórios estão associados a quedas em idosos vivendo na comunidade. MÉTODOS: Estudo da coorte de idosos de Bambuí, envolvendo 1.250 participantes da linha de base do projeto. Foram coletadas informações sobre quedas nos últimos 12 meses, classificadas quanto à ocorrência (única ou múltipla) e gravidade (procura por serviços de saúde). O inquérito também continha informações a respeito das características sociodemográficas, comportamentais e condições de saúde, as quais foram utilizadas como fatores de confusão. As exposições pesquisadas incluíram: interleucinas (IL-1β, IL-6, IL-8, IL-10 e IL-12), fator de necrose tumoral (TNF), proteína C reativa ultrassensível (PCRus) e quimiocinas (CXCL9, CCL5, CCL10 e MCP1). O tratamento dos dados foi realizado por meio de regressão logística, obtendose odds ratio e intervalo de 95% de confiança (IC95%). RESULTADOS: A prevalência de queda foi 27,1%; 40,1% dos idosos relataram quedas múltiplas e 33,3% procuraram serviços de saúde. Após ajustes, permaneceram associados às quedas os níveis elevados de PCRus (OR = 1,46; IC95% 1,04–2,03), CCL5 (OR = 1,38; IC95% 1,01–1,90) e CXCL9 (OR = 1,43; IC95% 1,02–2,02). Houve associação entre o número de marcadores elevados e a ocorrência de quedas: dois (OR = 1,47; IC95% 1,02–2,12) e três (OR = 2,08; IC95% 1,12–3,87) biomarcadores aumentados predisseram probabilidades de quedas iguais a 32,0% e 39,4%, respectivamente. CONCLUSÕES: Os níveis elevados de PCRus, CCL5 e CXCL9, que estiveram associados a quedas, podem contribuir para o adequado entendimento do mecanismo associado à ocorrência desse evento em idosos

Immunoregulatory mechanisms in Chagas disease: modulation of apoptosis in T-cell mediated immune responses

Submitted by Nuzia Santos ([email protected]) on 2017-07-17T17:53:45Z No. of bitstreams: 1 Chaves_AnaThereza_Immunoregulatory mechanisms_IRR_2016.pdf: 12736177 bytes, checksum: 7182dae7e3675c77254aa3dd4157a0a9 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2017-07-17T18:03:09Z (GMT) No. of bitstreams: 1 Chaves_AnaThereza_Immunoregulatory mechanisms_IRR_2016.pdf: 12736177 bytes, checksum: 7182dae7e3675c77254aa3dd4157a0a9 (MD5)Made available in DSpace on 2017-07-17T18:03:09Z (GMT). No. of bitstreams: 1 Chaves_AnaThereza_Immunoregulatory mechanisms_IRR_2016.pdf: 12736177 bytes, checksum: 7182dae7e3675c77254aa3dd4157a0a9 (MD5) Previous issue date: 2016Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Laboratório de Biologia das Interações Celulares. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina Programa de Pós graduação em Medicina Tropical e Infectologia. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Laboratório de Biologia das Interações Celulares. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Laboratório de Imunologia e Genômica de Parasitos. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Laboratório de Imunologia e Genômica de Parasitos. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Faculdade de Medicina Programa de Pós graduação em Medicina Tropical e Infectologia. Belo Horizonte, MG, Brazil.Laboratório de Imunologia Celular e Molecular, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brazil/Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Belo Horizonte, MG, Brazil/Universidade Federal de Ouro Preto. Ouro Preto, MG, Brazil.BACKGROUND: Chronic Chagas disease presents different clinical manifestations ranging from asymptomatic (namely indeterminate) to severe cardiac and/or digestive. Previous results have shown that the immune response plays an important role, although no all mechanisms are understood. Immunoregulatory mechanisms such as apoptosis are important for the control of Chagas disease, possibly affecting the morbidity in chronic clinical forms. Apoptosis has been suggested to be an important mechanism of cellular response during T. cruzi infection. We aimed to further understand the putative role of apoptosis in Chagas disease and its relation to the clinical forms of the disease. METHODS: Apoptosis of lymphocytes, under antigenic stimuli (soluble T. cruzi antigens - TcAg) where compared to that of non-stimulated cells. Apoptosis was evaluated using the expression of annexin and caspase 3(+) by T cells and the percentage of cells positive evaluated by flow cytometry. In addition activation and T cell markers were used for the identification of TCD4(+) and TCD8(+) subpopulations. The presence of intracellular and plasma cytokines were also evaluated. Analysis of the activation status of the peripheral blood cells showed that patients with Chagas disease presented higher levels of activation determined by the expression of activation markers, after TcAg stimulation. PCR array were used to evaluate the contribution of this mechanism in specific cell populations from patients with different clinical forms of human Chagas disease. RESULTS: Our results showed a reduced proliferative response associated a high expression of T CD4(+)CD62L(-) cells in CARD patients when compared with IND group and NI individuals. We also observed that both groups of patients presented a significant increase of CD4(+) and CD8(+) T cell subsets in undergoing apoptosis after in vitro stimulation with T. cruzi antigens. In CARD patients, both CD4(+) and CD8(+) T cells expressing TNF-α were highly susceptible to undergo apoptosis after in vitro stimulation. Interestingly, the in vitro TcAg stimulation increased considerably the expression of cell death TNF/TNFR superfamily and Caspase family receptors genes in CARD patients. CONCLUSIONS: Taken together, our results suggest that apoptosis may be an important mechanism for the control of morbidity in T. cruzi infection by modulating the expression of apoptosis genes, the cytokine environment and/or killing of effector cells

Validation of a yellow fever vaccine model using data from primary vaccination in children and adults, re-vaccination and dose-response in adults and studies with immunocompromised individuals

Background: An effective yellow fever (YF) vaccine has been available since 1937. Nevertheless, questions regarding its use remain poorly understood, such as the ideal dose to confer immunity against the disease, the need for a booster dose, the optimal immunisation schedule for immunocompetent, immunosuppressed, and pediatric populations, among other issues. This work aims to demonstrate that computational tools can be used to simulate different scenarios regarding YF vaccination and the immune response of individuals to this vaccine, thus assisting the response of some of these open questions. Results: This work presents the computational results obtained by a mathematical model of the human immune response to vaccination against YF. Five scenarios were simulated: primovaccination in adults and children, booster dose in adult individuals, vaccination of individuals with autoimmune diseases under immunomodulatory therapy, and the immune response to different vaccine doses. Where data were available, the model was able to quantitatively replicate the levels of antibodies obtained experimentally. In addition, for those scenarios where data were not available, it was possible to qualitatively reproduce the immune response behaviours described in the literature. Conclusions: Our simulations show that the minimum dose to confer immunity against YF is half of the reference dose. The results also suggest that immunological immaturity in children limits the induction and persistence of long-lived plasma cells are related to the antibody decay observed experimentally. Finally, the decay observed in the antibody level after ten years suggests that a booster dose is necessary to keep immunity against YF

New insights into Trypanosoma cruzi genetic diversity, and its influence on parasite biology and clinical outcomes

Chagas disease, caused by Trypanosoma cruzi, remains a serious public health problem worldwide. The parasite was subdivided into six distinct genetic groups, called “discrete typing units” (DTUs), from TcI to TcVI. Several studies have indicated that the heterogeneity of T. cruzi species directly affects the diversity of clinical manifestations of Chagas disease, control, diagnosis performance, and susceptibility to treatment. Thus, this review aims to describe how T. cruzi genetic diversity influences the biology of the parasite and/or clinical parameters in humans. Regarding the geographic dispersion of T. cruzi, evident differences were observed in the distribution of DTUs in distinct areas. For example, TcII is the main DTU detected in Brazilian patients from the central and southeastern regions, where there are also registers of TcVI as a secondary T. cruzi DTU. An important aspect observed in previous studies is that the genetic variability of T. cruzi can impact parasite infectivity, reproduction, and differentiation in the vectors. It has been proposed that T. cruzi DTU influences the host immune response and affects disease progression. Genetic aspects of the parasite play an important role in determining which host tissues will be infected, thus heavily influencing Chagas disease’s pathogenesis. Several teams have investigated the correlation between T. cruzi DTU and the reactivation of Chagas disease. In agreement with these data, it is reasonable to suppose that the immunological condition of the patient, whether or not associated with the reactivation of the T. cruzi infection and the parasite strain, may have an important role in the pathogenesis of Chagas disease. In this context, understanding the genetics of T. cruzi and its biological and clinical implications will provide new knowledge that may contribute to additional strategies in the diagnosis and clinical outcome follow-up of patients with Chagas disease, in addition to the reactivation of immunocompromised patients infected with T. cruzi