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[PMID]:29316479
[Au] Autor:Melicherová J; Hofmannová L; Valigurová A
[Ad] Endereço:Department of Botany and Zoology, Faculty of Science, Masaryk University, Kotlárská 2, 611 37 Brno, Czech Republic.
[Ti] Título:Response of cell lines to actual and simulated inoculation with Cryptosporidium proliferans.
[So] Source:Eur J Protistol;62:101-121, 2018 Feb.
[Is] ISSN:1618-0429
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The need for an effective treatment against cryptosporidiosis has triggered studies in the search for a working in vitro model. The peculiar niche of cryptosporidia at the brush border of host epithelial cells has been the subject of extensive debates. Despite extensive research on the invasion process, it remains enigmatic whether cryptosporidian host-parasite interactions result from an active invasion process or through encapsulation. We used HCT-8 and HT-29 cell lines for in vitro cultivation of the gastric parasite Cryptosporidium proliferans strain TS03. Using electron and confocal laser scanning microscopy, observations were carried out 24, 48 and 72 h after inoculation with a mixture of C. proliferans oocysts and sporozoites. Free sporozoites and putative merozoites were observed apparently searching for an appropriate infection site. Advanced stages, corresponding to trophozoites and meronts/gamonts enveloped by parasitophorous sac, and emptied sacs were detected. As our observations showed that even unexcysted oocysts became enveloped by cultured cell projections, using polystyrene microspheres, we evaluated the response of cell lines to simulated inoculation with cryptosporidian oocysts to verify innate and parasite-induced behaviour. We found that cultured cell encapsulation of oocysts is induced by parasite antigens, independent of any active invasion/motility.
[Mh] Termos MeSH primário: Cryptosporidium/fisiologia
Interações Hospedeiro-Parasita/fisiologia
[Mh] Termos MeSH secundário: Antígenos de Protozoários/metabolismo
Linhagem Celular
Criptosporidiose/metabolismo
Criptosporidiose/parasitologia
Células HT29
Seres Humanos
Microscopia Confocal
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Protozoan)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE


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[PMID]:29342212
[Au] Autor:Chaorattanakawee S; Nuchnoi P; Hananantachai H; Tumkosit U; Saunders D; Naka I; Ohashi J; Patarapotikul J
[Ad] Endereço:Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Rangsit, Patumthani, Thailand.
[Ti] Título:Sequence variation in Plasmodium falciparum merozoite surface protein-2 is associated with virulence causing severe and cerebral malaria.
[So] Source:PLoS One;13(1):e0190418, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Parasite virulence, an important factor contributing to the severity of Plasmodium falciparum infection, varies among P. falciparum strains. Relatively little is known regarding markers of virulence capable of identifying strains responsible for severe malaria. We investigated the effects of genetic variations in the P.f. merozoite surface protein 2 gene (msp2) on virulence, as it was previously postulated as a factor. We analyzed 300 msp2 sequences of single P. falciparum clone infection from patients with uncomplicated disease as well as those admitted for severe malaria with and without cerebral disease. The association of msp2 variations with disease severity was examined. We found that the N allele at codon 8 of Block 2 in the FC27-like msp2 gene was significantly associated with severe disease without cerebral complications (odds ratio = 2.73, P = 0.039), while the K allele at codon 17 of Block 4 in the 3D7-like msp2 gene was associated with cerebral malaria (odds ratio = 3.52, P = 0.024). The data suggests possible roles for the associated alleles on parasite invasion processes and immune-mediated pathogenicity. Multiplicity of infection was found to associate with severe disease without cerebral complications, but not cerebral malaria. Variations in the msp2-FC27-block 2-8N and 3D7-block 4-17K allele appear to be parasite virulence markers, and may be useful in determining the likelihood for severe and cerebral malaria. Their interactions with potential host factors for severe diseases should also be explored.
[Mh] Termos MeSH primário: Antígenos de Protozoários/genética
Malária Cerebral/parasitologia
Plasmodium falciparum/genética
Proteínas de Protozoários/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Antígenos de Protozoários/química
Sequência de Bases
Seres Humanos
Plasmodium falciparum/patogenicidade
Proteínas de Protozoários/química
Alinhamento de Sequência
Virulência
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, Protozoan); 0 (Protozoan Proteins); 0 (merozoite surface protein 2, Plasmodium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190418


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[PMID]:29329308
[Au] Autor:Fernandez-Arias C; Arias CF; Zhang M; Herrero MA; Acosta FJ; Tsuji M
[Ad] Endereço:HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY, United States of America.
[Ti] Título:Modeling the effect of boost timing in murine irradiated sporozoite prime-boost vaccines.
[So] Source:PLoS One;13(1):e0190940, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Vaccination with radiation-attenuated sporozoites has been shown to induce CD8+ T cell-mediated protection against pre-erythrocytic stages of malaria. Empirical evidence suggests that successive inoculations often improve the efficacy of this type of vaccines. An initial dose (prime) triggers a specific cellular response, and subsequent inoculations (boost) amplify this response to create a robust CD8+ T cell memory. In this work we propose a model to analyze the effect of T cell dynamics on the performance of prime-boost vaccines. This model suggests that boost doses and timings should be selected according to the T cell response elicited by priming. Specifically, boosting during late stages of clonal contraction would maximize T cell memory production for vaccines using lower doses of irradiated sporozoites. In contrast, single-dose inoculations would be indicated for higher vaccine doses. Experimental data have been obtained that support theoretical predictions of the model.
[Mh] Termos MeSH primário: Vacinas Antimaláricas/imunologia
Esporozoítos/imunologia
[Mh] Termos MeSH secundário: Animais
Anopheles/parasitologia
Antígenos de Protozoários/imunologia
Linfócitos T CD8-Positivos/imunologia
Feminino
Memória Imunológica
Camundongos
Mosquitos Vetores
Plasmodium yoelii/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antigens, Protozoan); 0 (Malaria Vaccines)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190940


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[PMID]:29309786
[Au] Autor:Hijjawi N; Yang R; Hatmal M; Yassin Y; Mharib T; Mukbel R; Mahmoud SA; Al-Shudifat AE; Ryan U
[Ad] Endereço:Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, The Hashemite University, PO Box 150459, Zarqa, 13115, Jordan.
[Ti] Título:Comparison of ELISA, nested PCR and sequencing and a novel qPCR for detection of Giardia isolates from Jordan.
[So] Source:Exp Parasitol;185:23-28, 2018 Feb.
[Is] ISSN:1090-2449
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Little is known about the prevalence of Giardia duodenalis in human patients in Jordan and all previous studies have used direct microscopy, which lacks sensitivity. The present study developed a novel quantitative PCR (qPCR) assay at the ß-giardin (bg) locus and evaluated its use as a frontline test for the diagnosis of giardiasis in comparison with a commercially available ELISA using nested PCR and sequencing of the glutamate dehydrogenase (gdh) locus (gdh nPCR) as the gold standard. A total of 96 human faecal samples were collected from 96 patients suffering from diarrhoea from 5 regions of Jordan and were screened using the ELISA and qPCR. The analytical specificity of the bg qPCR assay revealed no cross-reactions with other genera and detected all the Giardia isolates tested. Analytical sensitivity was 1 Giardia cyst per µl of DNA extract. The overall prevalence of Giardia was 64.6%. The clinical sensitivity and specificity of the bg qPCR was 89.9% and 82.9% respectively compared to 76.5 and 68.0% for the ELISA. This study is the first to compare three different methods (ELISA, bg qPCR, nested PCR and sequencing at the gdh locus) to diagnose Jordanian patients suffering from giardiasis and to analyze their demographic data.
[Mh] Termos MeSH primário: Diarreia/parasitologia
Giardia lamblia/isolamento & purificação
Giardíase/parasitologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Antígenos de Protozoários/análise
Criança
Pré-Escolar
Cólica/parasitologia
Proteínas do Citoesqueleto/genética
DNA de Protozoário/química
DNA de Protozoário/isolamento & purificação
Ensaio de Imunoadsorção Enzimática
Fezes/parasitologia
Feminino
Giardia lamblia/genética
Giardia lamblia/imunologia
Giardíase/epidemiologia
Glutamato Desidrogenase
Seres Humanos
Lactente
Jordânia/epidemiologia
Masculino
Meia-Idade
Reação em Cadeia da Polimerase
Prevalência
Proteínas de Protozoários/genética
Reação em Cadeia da Polimerase em Tempo Real
Sensibilidade e Especificidade
Vômito/parasitologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Protozoan); 0 (Cytoskeletal Proteins); 0 (DNA, Protozoan); 0 (Protozoan Proteins); 0 (giardin protein, Giardia lamblia); EC 1.4.1.2 (Glutamate Dehydrogenase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE


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[PMID]:29309783
[Au] Autor:Picchio MS; Sánchez VR; Arcon N; Soto AS; Perrone Sibilia M; Aldirico MLA; Urrutia M; Moretta R; Fenoy IM; Goldman A; Martin V
[Ad] Endereço:Laboratorio de Inmunología, Vacunas y Alergia, CESyMA, Escuela de Ciencia y Tecnología, Universidad Nacional de San Martín, Campus Migueletes, Martín de Irigoyen 3100 C.P., 1650 San Martín, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2290
[Ti] Título:Vaccine potential of antigen cocktails composed of recombinant Toxoplasma gondii TgPI-1, ROP2 and GRA4 proteins against chronic toxoplasmosis in C3H mice.
[So] Source:Exp Parasitol;185:62-70, 2018 Feb.
[Is] ISSN:1090-2449
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The development of an effective and safe vaccine to prevent Toxoplasma gondii infection is an important aim due to the great clinical and economic impact of this parasitosis. We have previously demonstrated that immunization with the serine protease inhibitor-1 (TgPI-1) confers partial protection to C3H/HeN and C57BL/6 mice. In order to improve the level of protection, in this work, we combined this novel antigen with ROP2 and/or GRA4 recombinant proteins (rTgPI-1+rROP2, rTgPI-1+rGRA4, rTgPI-1+rROP2+rGRA4) to explore the best combination against chronic toxoplasmosis in C3H/HeN mice. All tested vaccine formulations, administered following a homologous prime-boost protocol that combines intradermal and intranasal routes, conferred partial protection as measured by the reduction of brain cyst burden following oral challenge with tissue cysts of Me49 T. gondii strain. The highest level of protection was achieved by the mixture of rTgPI-1 and rROP2 proteins with an average parasite burden reduction of 50% compared to the unvaccinated control group. The vaccine-induced protective effect was related to the elicitation of systemic cellular and humoral immune responses that included antigen-specific spleen cell proliferation, the release of Th1/Th2 cytokines, and the generation of antigen-specific antibodies in serum. Additionally, mucosal immune responses were also induced, characterized by secretion of antigen-specific IgA antibodies in intestinal lavages and specific mesenteric lymph node cell proliferation. Our results demonstrate that rTgPI-1+rROP2 antigens seem a promising mixture to be combined with other immunogenic proteins in a multiantigenic vaccine formulation against toxoplasmosis.
[Mh] Termos MeSH primário: Antígenos de Protozoários/imunologia
Vacinas Protozoárias/normas
Toxoplasma/imunologia
Toxoplasmose Animal/prevenção & controle
[Mh] Termos MeSH secundário: Animais
Anticorpos Antiprotozoários/sangue
Linhagem Celular
Doença Crônica
Citocinas/metabolismo
Feminino
Fibroblastos/parasitologia
Prepúcio do Pênis/citologia
Seres Humanos
Imunoglobulina A Secretora/análise
Imunoglobulina G/sangue
Mucosa Intestinal/imunologia
Masculino
Proteínas de Membrana/imunologia
Camundongos
Camundongos Endogâmicos C3H
Proteínas de Protozoários/imunologia
Baço/citologia
Baço/imunologia
Vacinas Sintéticas/normas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Protozoan); 0 (Antigens, Protozoan); 0 (Cytokines); 0 (GRA4 protein, Toxoplasma gondii); 0 (Immunoglobulin A, Secretory); 0 (Immunoglobulin G); 0 (Membrane Proteins); 0 (Protozoan Proteins); 0 (Protozoan Vaccines); 0 (ROP 2 protein, Toxoplasma gondii); 0 (TgPI protein, Toxoplasma gondii); 0 (Vaccines, Synthetic)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE


  6 / 12751 MEDLINE  
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[PMID]:29281708
[Au] Autor:Scaria PV; Chen B; Rowe CG; Jones DS; Barnafo E; Fischer ER; Anderson C; MacDonald NJ; Lambert L; Rausch KM; Narum DL; Duffy PE
[Ad] Endereço:Laboratory of Malaria Immunology and Vaccinology, NIAID, National Institutes of Health, Rockville, Maryland, United States of America.
[Ti] Título:Protein-protein conjugate nanoparticles for malaria antigen delivery and enhanced immunogenicity.
[So] Source:PLoS One;12(12):e0190312, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chemical conjugation of polysaccharide to carrier proteins has been a successful strategy to generate potent vaccines against bacterial pathogens. We developed a similar approach for poorly immunogenic malaria protein antigens. Our lead candidates in clinical trials are the malaria transmission blocking vaccine antigens, Pfs25 and Pfs230D1, individually conjugated to the carrier protein Exoprotein A (EPA) through thioether chemistry. These conjugates form nanoparticles that show enhanced immunogenicity compared to unconjugated antigens. In this study, we examined the broad applicability of this technology as a vaccine development platform, by comparing the immunogenicity of conjugates prepared by four different chemistries using different malaria antigens (PfCSP, Pfs25 and Pfs230D1), and carriers such as EPA, TT and CRM197. Several conjugates were synthesized using thioether, amide, ADH and glutaraldehyde chemistries, characterized for average molecular weight and molecular weight distribution, and evaluated in mice for humoral immunogenicity. Conjugates made with the different chemistries, or with different carriers, showed no significant difference in immunogenicity towards the conjugated antigens. Since particle size can influence immunogenicity, we tested conjugates with different average size in the range of 16-73 nm diameter, and observed greater immunogenicity of smaller particles, with significant differences between 16 and 73 nm particles. These results demonstrate the multiple options with respect to carriers and chemistries that are available for protein-protein conjugate vaccine development.
[Mh] Termos MeSH primário: Antígenos de Protozoários/administração & dosagem
Nanopartículas
Proteínas/química
[Mh] Termos MeSH secundário: Animais
Anticorpos Antiprotozoários/biossíntese
Antígenos de Protozoários/imunologia
Camundongos
Tamanho da Partícula
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., INTRAMURAL
[Nm] Nome de substância:
0 (Antibodies, Protozoan); 0 (Antigens, Protozoan); 0 (Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190312


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[PMID]:29246832
[Au] Autor:Marques T; Silva GC; Henrique Paiva PM; Nascentes GAN; Ramirez LE; Norris K; Meira WSF
[Ad] Endereço:Programa de Pós-graduação em Medicina Tropical e Infectologia, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil.
[Ti] Título:Use of Tc-rCRP as a target for lytic antibody titration after experimental Trypanosoma cruzi infection.
[So] Source:Exp Parasitol;184:103-108, 2018 Jan.
[Is] ISSN:1090-2449
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Experimental Chagas disease has been used as a model to identify several host/parasite interaction factors involved in immune responses to Trypanosoma cruzi infection. One of the factors inherent to this parasite is the complement regulatory protein (Tc-CRP), a major epitope that induces production of lytic antibodies during T. cruzi infections. Previous studies have evaluated the function of Tc-CRP as an antigenic marker via ELISAs, which demonstrated high sensitivity and specificity when compared to other methods. Therefore, this study aimed to assess and compare the levels of lytic antibodies induced by this protein following experimental infection using different T. cruzi strains. Our results demonstrated that infections induced by strains isolated from vectors resulted in subpatent parasitaemia and low reactivity, as assessed by Tc-rCRP ELISAs. On the other hand, mice inoculated with T. cruzi strains isolated from patients developed patent parasitaemia, and presented elevated lytic antibodies titres, as measured by Tc-rCRP ELISA. In addition, comparison between different mouse lineages demonstrated that Balb/c mice were more reactive than C57BL/6 mice in almost all types of infections, except those infected by the AQ-4 strain. Parasites from the Hel strain generated the greatest lytic antibody response in all evaluated models. Therefore, application of sensitive techniques for monitoring immune responses would enable us to establish growth curves for lytic antibodies during the course of the infection, and allow us to discriminate between T. cruzi strains that originate from different hosts.
[Mh] Termos MeSH primário: Anticorpos Antiprotozoários/análise
Antígenos de Protozoários/imunologia
Doença de Chagas/imunologia
Proteínas de Protozoários/imunologia
Trypanosoma cruzi/imunologia
[Mh] Termos MeSH secundário: Animais
Biomarcadores/análise
Ensaio de Imunoadsorção Enzimática
Epitopos/imunologia
Interações Hospedeiro-Parasita/imunologia
Seres Humanos
Insetos Vetores/parasitologia
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Parasitemia/imunologia
Parasitemia/parasitologia
Sensibilidade e Especificidade
Triatominae/parasitologia
Trypanosoma cruzi/classificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Protozoan); 0 (Antigens, Protozoan); 0 (Biomarkers); 0 (Epitopes); 0 (Protozoan Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180205
[Lr] Data última revisão:
180205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171217
[St] Status:MEDLINE


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[PMID]:28468680
[Au] Autor:Ferraz R; Cunha CF; Pimentel MIF; Lyra MR; Pereira-Da-Silva T; Schubach AO; Da-Cruz AM; Bertho AL
[Ad] Endereço:Laboratory of Immunoparasitology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil.
[Ti] Título:CD3 CD4 CD8 (double negative) T lymphocytes and NKT cells as the main cytotoxic-related-CD107a cells in lesions of cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis.
[So] Source:Parasit Vectors;10(1):219, 2017 May 03.
[Is] ISSN:1756-3305
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cutaneous leishmaniasis (CL) is caused by Leishmania (Viannia) braziliensis, which infects dermal macrophages and dendritic cells, causing an intense immune-mediated-tissue inflammation and a skin ulcer with elevated borders that can heal spontaneously or after antimonial therapy. The resolution of lesions depends on an adaptive immune response, and cytotoxic cells seem to have a fundamental role in this process. The aim of this study is to better understand the role of cytotoxicity mediated mechanisms that occur during the immune response in the CL lesion milieu, considering distinct cytotoxic-related CD107a cells, such as CD8 , CD4 , CD4 CD8 (double-negative, DN) and CD4 CD8 (double-positive, DP) T lymphocytes, as well as NK and NKT cells. METHODS: Lesion derived cells were assessed for T cell subpopulations and NK cells, as well as CD107a expression by flow cytometry. In addition, cytometric bead array (CBA) was used to quantify cytokines and granzyme B concentrations in supernatants from macerated lesions. RESULTS: Flow cytometry analyses revealed that NKT cells are the major CD107a-expressing cell population committed to cytotoxicity in CL lesion, although we also observed high frequencies of CD4 and DN T cells expressing CD107a. Analysing the pool of CD107a -cell populations, we found a higher distribution of DN T cells (44%), followed by approximately 25% of NKT cells. Interestingly, NK and CD8 T cells represented only 3 and 4% of the total-CD107a -cell pool, respectively. CONCLUSIONS: The cytotoxicity activity that occurs in the lesion milieu of CL patients seems to be dominated by DN T and NKT cells. These findings suggest the need for a reevaluation of the role of classical-cytotoxic NK and CD8 T cells in the pathogenesis of CL, implicating an important role for other T cell subpopulations.
[Mh] Termos MeSH primário: Citotoxicidade Imunológica
Leishmaniose Cutânea/imunologia
Proteína 1 de Membrana Associada ao Lisossomo/imunologia
Células T Matadoras Naturais/imunologia
Subpopulações de Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Adulto
Antígenos de Protozoários/imunologia
Biópsia
Brasil/epidemiologia
Citocinas/biossíntese
Citocinas/genética
Feminino
Citometria de Fluxo
Granzimas/análise
Seres Humanos
Leishmania braziliensis/imunologia
Leishmaniose Cutânea/epidemiologia
Proteína 1 de Membrana Associada ao Lisossomo/genética
Masculino
Meia-Idade
Pele/imunologia
Pele/parasitologia
Pele/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Protozoan); 0 (Cytokines); 0 (Lysosomal-Associated Membrane Protein 1); EC 3.4.21.- (GZMB protein, human); EC 3.4.21.- (Granzymes)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180205
[Lr] Data última revisão:
180205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1186/s13071-017-2152-2


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[PMID]:28449641
[Au] Autor:Plewes K; Kingston HWF; Ghose A; Maude RJ; Herdman MT; Leopold SJ; Ishioka H; Hasan MMU; Haider MS; Alam S; Piera KA; Charunwatthana P; Silamut K; Yeo TW; Faiz MA; Lee SJ; Mukaka M; Turner GDH; Anstey NM; Jackson Roberts L; White NJ; Day NPJ; Hossain MA; Dondorp AM
[Ad] Endereço:Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
[Ti] Título:Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study.
[So] Source:BMC Infect Dis;17(1):313, 2017 04 27.
[Is] ISSN:1471-2334
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Intravascular hemolysis is an intrinsic feature of severe malaria pathophysiology but the pathogenic role of cell-free hemoglobin-mediated oxidative stress in severe malaria associated acute kidney injury (AKI) is unknown. METHODS: As part of a prospective observational study, enrolment plasma cell-free hemoglobin (CFH), lipid peroxidation markers (F -isoprostanes (F -IsoPs) and isofurans (IsoFs)), red cell deformability, and serum creatinine were quantified in Bangladeshi patients with severe falciparum malaria (n = 107), uncomplicated malaria (n = 80) and sepsis (n = 28). The relationships between these indices and kidney function and clinical outcomes were examined. RESULTS: AKI was diagnosed at enrolment in 58% (62/107) of consecutive patients with severe malaria, defined by an increase in creatinine ≥1.5 times expected baseline. Severe malaria patients with AKI had significantly higher plasma cell-free hemoglobin (geometric mean CFH: 8.8 µM; 95% CI, 6.2-12.3 µM), F -isoprostane (56.7 pg/ml; 95% CI, 45.3-71.0 pg/ml) and isofuran (109.2 pg/ml; 95% CI, 85.1-140.1 pg/ml) concentrations on enrolment compared to those without AKI (CFH: 5.1 µM; 95% CI, 4.0-6.6 µM; P = 0.018; F -IsoPs: 27.8 pg/ml; 95% CI, 23.7-32.7 pg/ml; P < 0.001; IsoFs: 41.7 pg/ml; 95% CI, 30.2-57.6 pg/ml; P < 0.001). Cell-free hemoglobin correlated with markers of hemolysis, parasite burden (P. falciparum histidine rich protein 2 (PfHRP2)), and F -IsoPs. Plasma F -IsoPs and IsoFs inversely correlated with pH, positively correlated with creatinine, PfHRP2 and fractional excretion of sodium, and were higher in patients later requiring hemodialysis. Plasma F -IsoP concentrations also inversely correlated with red cell deformability and were higher in fatal cases. Mixed effects modeling including an interaction term for CFH and time showed that F -IsoPs, IsoFs, PfHRP2, CFH, and red cell rigidity were independently associated with increasing creatinine over 72 h. Multivariable logistic regression showed that admission F -IsoPs, IsoFs and red cell deformability were associated with the need for subsequent hemodialysis. CONCLUSIONS: Cell-free hemoglobin and lipid peroxidation are associated with acute kidney injury and disease severity in falciparum malaria, suggesting a pathophysiological role in renal tubular injury. Evaluation of adjunctive therapies targeting cell-free hemoglobin-mediated oxidative stress is warranted.
[Mh] Termos MeSH primário: Lesão Renal Aguda/etiologia
Hemoglobinas/metabolismo
Malária Falciparum/metabolismo
Estresse Oxidativo
[Mh] Termos MeSH secundário: Lesão Renal Aguda/mortalidade
Lesão Renal Aguda/terapia
Adulto
Antígenos de Protozoários/sangue
Biomarcadores/sangue
Creatinina/sangue
Eritrócitos/patologia
F2-Isoprostanos/sangue
F2-Isoprostanos/urina
Feminino
Seres Humanos
Peroxidação de Lipídeos
Malária Falciparum/complicações
Malária Falciparum/mortalidade
Masculino
Meia-Idade
Estudos Prospectivos
Proteínas de Protozoários/sangue
Diálise Renal
Sepse/sangue
Sepse/etiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, Protozoan); 0 (Biomarkers); 0 (F2-Isoprostanes); 0 (HRP-2 antigen, Plasmodium falciparum); 0 (Hemoglobins); 0 (Protozoan Proteins); AYI8EX34EU (Creatinine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180120
[Lr] Data última revisão:
180120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1186/s12879-017-2373-1


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[PMID]:29211247
[Au] Autor:Cabral FJ; Vianna LG; Medeiros MM; Carlos BC; Martha RD; Silva NM; Silva LHPD; Stabeli RG; Wunderlich G
[Ad] Endereço:Universidade Estadual de Campinas, Instituto de Biologia, Departamento de Biologia Animal, Campinas, SP, Brasil.
[Ti] Título:Immunoproteomics of Plasmodium falciparum-infected red blood cell membrane fractions.
[So] Source:Mem Inst Oswaldo Cruz;112(12):850-856, 2017 Dec.
[Is] ISSN:1678-8060
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The surface of infected red blood cells (iRBCs) has been widely investigated because of the molecular complexity and pathogenesis mechanisms involved. Asymptomatic individuals are important in the field because they can perpetuate transmission as natural reservoirs and present a challenge for diagnosing malaria because of their low levels of circulating parasites. Recent studies of iRBC antibody recognition have shown that responses are quantitatively similar in symptomatic and asymptomatic infections, but no studies have characterised the plasmodial proteins targeted by this response. OBJECTIVES: Our main objective was to identify Plasmodium falciparum proteins associated with iRBC ghosts recognised by antibodies in the sera of symptomatic and asymptomatic individuals in the Brazilian Amazon. METHODS: We collected symptomatic and asymptomatic sera from patients residing in the Brazilian Amazon and P. falciparum iRBC ghosts to identify the proteins involved in natural antibody recognition by 2D-electrophoresis, western blotting, and high- resolution mass spectrometry. FINDINGS: 2D gel-based immunoproteome analysis using symptomatic and asymptomatic sera identified 11 proteins with at least one unique peptide, such as chaperones HSP70-1 and HSP70-x, which likely are components of the secretion machinery/PTEX translocon. PfEMP1 is involved in antigenic variation in symptomatic infections and we found putative membrane proteins whose functions are unknown. MAIN FINDINGS: Our results suggest a potential role of old and new proteins, such as antigenic variation proteins, iRBC remodelling, and membrane proteins, with no assigned functions related to the immune response against P. falciparum, providing insights into the pathogenesis, erythrocyte remodelling, and secretion machinery important for alternative diagnosis and/or malaria therapy.
[Mh] Termos MeSH primário: Anticorpos Antiprotozoários/genética
Antígenos de Protozoários/genética
Membrana Eritrocítica/parasitologia
Plasmodium falciparum/imunologia
[Mh] Termos MeSH secundário: Anticorpos Antiprotozoários/imunologia
Antígenos de Protozoários/imunologia
Infecções Assintomáticas
Western Blotting
Eletroforese em Gel Bidimensional
Membrana Eritrocítica/imunologia
Seres Humanos
Espectrometria de Massas
Plasmodium falciparum/genética
Proteômica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Protozoan); 0 (Antigens, Protozoan)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171227
[Lr] Data última revisão:
171227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE



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