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[PMID]:29326050
[Au] Autor:Nayak A; Akpunarlieva S; Barrett M; Burchmore R
[Ad] Endereço:Institute of Infection, Immunity and Inflammation and Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
[Ti] Título:A defined medium for Leishmania culture allows definition of essential amino acids.
[So] Source:Exp Parasitol;185:39-52, 2018 Feb.
[Is] ISSN:1090-2449
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Axenic culture of Leishmania is generally performed in rich, serum-supplemented media which sustain robust growth over multiple passages. The use of such undefined media, however, obscures proteomic analyses and confounds the study of metabolism. We have established a simple, defined culture medium that supports the sustained growth of promastigotes over multiple passages and which yields parasites that have similar infectivity to macrophages to parasites grown in a conventional semi-defined medium. We have exploited this medium to investigate the amino acid requirements of promastigotes in culture and have found that phenylalanine, tryptophan, arginine, leucine, lysine and valine are essential for viability in culture. Most of the 20 proteogenic amino acids promote growth of Leishmania promastigotes, with the exception of alanine, asparagine, and glycine. This defined medium will be useful for further studies of promastigote substrate requirements, and will facilitate future proteomic and metabolomic analyses.
[Mh] Termos MeSH primário: Aminoácidos Essenciais/metabolismo
Meios de Cultura/química
Leishmania/crescimento & desenvolvimento
[Mh] Termos MeSH secundário: Anfotericina B/farmacologia
Animais
Antiprotozoários/farmacologia
Concentração Inibidora 50
Leishmania/efeitos dos fármacos
Leishmania donovani/crescimento & desenvolvimento
Leishmania major/crescimento & desenvolvimento
Leishmania mexicana/crescimento & desenvolvimento
Metotrexato/farmacologia
Pentamidina/farmacologia
Inoculações Seriadas
Especificidade da Espécie
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids, Essential); 0 (Antiprotozoal Agents); 0 (Culture Media); 673LC5J4LQ (Pentamidine); 7XU7A7DROE (Amphotericin B); YL5FZ2Y5U1 (Methotrexate)
[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:180113
[St] Status:MEDLINE


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[PMID]:29191699
[Au] Autor:Nieto-Meneses R; Castillo R; Hernández-Campos A; Maldonado-Rangel A; Matius-Ruiz JB; Trejo-Soto PJ; Nogueda-Torres B; Dea-Ayuela MA; Bolás-Fernández F; Méndez-Cuesta C; Yépez-Mulia L
[Ad] Endereço:Departamento de Parasitología, ENCB-IPN, 11340 Mexico City, Mexico; Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias-Pediatría, Instituto Mexicano del Seguro Social, 06720 Mexico City, Mexico.
[Ti] Título:In vitro activity of new N-benzyl-1H-benzimidazol-2-amine derivatives against cutaneous, mucocutaneous and visceral Leishmania species.
[So] Source:Exp Parasitol;184:82-89, 2018 Jan.
[Is] ISSN:1090-2449
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The identification of specific therapeutic targets and the development of new drugs against leishmaniasis are urgently needed, since chemotherapy currently available for its treatment has several problems including many adverse side effects. In an effort to develop new antileishmanial drugs, in the present study a series of 28 N-benzyl-1H-benzimidazol-2-amine derivatives was synthesized and evaluated in vitro against Leishmania mexicana promastigotes. Compounds 7 and 8 with the highest antileishmanial activity (micromolar) and lower cytotoxicity than miltefosine and amphotericin B were selected to evaluate their activity against L. braziliensis 9and L. donovani, species causative of mucocutaneous and visceral leishmaniasis, respectively. Compound 7 showed significantly higher activity against L. braziliensis promastigotes than compound 8 and slightly lower than miltefosine. Compounds 7 and 8 had IC values in the micromolar range against the amastigote of L. mexicana and L. braziliensis. However, both compounds did not show better activity against L. donovani than miltefosine. Compound 8 showed the highest SI against both parasite stages of L. mexicana. In addition, compound 8 inhibited 68.27% the activity of recombinant L. mexicana arginase (LmARG), a therapeutic target for the treatment of leishmaniasis. Docking studies were also performed in order to establish the possible mechanism of action by which this compound exerts its inhibitory effect. Compound 8 shows promising potential for the development of more potent antileishmanial benzimidazole derivatives.
[Mh] Termos MeSH primário: Antiprotozoários/farmacologia
Benzimidazóis/farmacologia
Leishmania braziliensis/efeitos dos fármacos
Leishmania donovani/efeitos dos fármacos
Leishmania mexicana/efeitos dos fármacos
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Anfotericina B/farmacologia
Animais
Antiprotozoários/toxicidade
Arginase/antagonistas & inibidores
Arginase/química
Benzimidazóis/síntese química
Benzimidazóis/química
Benzimidazóis/toxicidade
Linhagem Celular
Concentração Inibidora 50
Leishmania mexicana/enzimologia
Leishmaniose Cutânea/tratamento farmacológico
Leishmaniose Cutânea/parasitologia
Leishmaniose Mucocutânea/tratamento farmacológico
Leishmaniose Mucocutânea/parasitologia
Leishmaniose Visceral/tratamento farmacológico
Leishmaniose Visceral/parasitologia
Macrófagos/efeitos dos fármacos
Camundongos
Simulação de Acoplamento Molecular
Fosforilcolina/análogos & derivados
Fosforilcolina/farmacologia
Alinhamento de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiprotozoal Agents); 0 (Benzimidazoles); 107-73-3 (Phosphorylcholine); 53EY29W7EC (miltefosine); 7XU7A7DROE (Amphotericin B); EC 3.5.3.1 (Arginase)
[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:171202
[St] Status:MEDLINE


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[PMID]:29324760
[Au] Autor:Poché DM; Garlapati RB; Mukherjee S; Torres-Poché Z; Hasker E; Rahman T; Bharti A; Tripathi VP; Prakash S; Chaubey R; Poché RM
[Ad] Endereço:Department of Vector Ecology, Genesis Laboratories, Inc., Wellington, United States of America.
[Ti] Título:Bionomics of Phlebotomus argentipes in villages in Bihar, India with insights into efficacy of IRS-based control measures.
[So] Source:PLoS Negl Trop Dis;12(1):e0006168, 2018 01.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Visceral leishmaniasis (VL) is a deadly vector-borne disease. Approximately 90% of Indian VL cases occur in Bihar, where the sand fly, Phlebotomus argentipes, is the principal vector. Sand fly control in Bihar consists of indoor residual spraying (IRS), the practice of spraying the inner walls of village dwellings with insecticides. Prior researchers have evaluated success of IRS-control by estimating vector abundance in village houses, but the number of sampling periods (n = 2-3) were minimal, and outdoor-resting P. argentipes were neglected. We describe a large-scale field study, performed in 24 villages within two Bihari districts, during which P. argentipes were collected biweekly over 47-weeks, in cattle enclosures, houses, and outdoors in peri-domestic vegetation. The objectives of this study were to provide updated P. argentipes ecological field data, and determine if program-initiated IRS-treatment had led to noticeable differences in vector abundance. PRINCIPAL FINDINGS: P. argentipes (n = 126,901) relative abundance was greatest during the summer months (June-August) when minimum temperatures were highest. P. argentipes were most frequently collected from cattle enclosures (~46% total; ~56% blood fed). Many sand flies were found to have taken blood from multiple sources, with ~81% having blood fed on humans and ~60% blood feeding on bovines. Nonparametric statistical tests were determined most appropriate for evaluating IRS-treatment. Differences in P. argentipes abundance in houses, cattle enclosures and vegetation were detected between IRS-treated and untreated villages in only ~9% of evaluation periods occurring during the peak period of human-vector exposure (June-August) and in ~8% of the total observations. No significant differences were detected between the numbers of P. argentipes collected in vegetation close to the experimental villages. CONCLUSION: The results of this study provide updated data regarding P. argentipes seasonal abundance, spatial distribution, and host preferances, and suggest vector abundance has not significantly declined in IRS-treated villages. We suggest that IRS be supplemented with vector control strategies targeting exophagic, exophilic P. argentipes, and that disease surveillance be accompanied by rigorous vector population monitoring.
[Mh] Termos MeSH primário: Controle de Insetos/métodos
Insetos Vetores/efeitos dos fármacos
Inseticidas/farmacologia
Leishmaniose Visceral/prevenção & controle
Leishmaniose Visceral/transmissão
Phlebotomus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Meio Ambiente
Seres Humanos
Índia/epidemiologia
Insetos Vetores/parasitologia
Leishmania donovani
Leishmaniose Visceral/epidemiologia
Leishmaniose Visceral/parasitologia
Phlebotomus/parasitologia
Estações do Ano
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Insecticides)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006168


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[PMID]:29187586
[Au] Autor:Banerjee A; Bhattacharya P; Dagur PK; Karmakar S; Ismail N; Joshi AB; Akue AD; KuKuruga M; McCoy JP; Dey R; Nakhasi HL
[Ad] Endereço:Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993.
[Ti] Título:Live Attenuated Centrin Gene-Deleted Parasites Induce IL-23-Dependent IL-17-Protective Immune Response against Visceral Leishmaniasis in a Murine Model.
[So] Source:J Immunol;200(1):163-176, 2018 01 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:No vaccine exists against visceral leishmaniasis. To develop effective vaccines, we have previously reported protective role of live attenuated centrin gene-deleted ( ) parasites through induction of Th1 type immune response in mice, hamsters, and dogs. In this study, we specifically explored the role of Th17 cells in -induced host protection in mice. Our results showed that compared with wild-type infection, parasites induce significantly higher expression of Th17 differentiation cytokines in splenic dendritic cells. There was also induction of IL-17 and its promoting cytokines in total splenocytes and in both CD4 and CD8 T cells following immunization with Upon challenge with wild-type parasites, IL-17 and its differentiating cytokines were significantly higher in -immunized mice compared with nonimmunized mice that resulted in parasite control. Alongside IL-17 induction, we observed induction of IFN-γ-producing Th1 cells as reported earlier. However, Th17 cells are generated before Th1 cells. Neutralization of either IL-17 or IFN-γ abrogated -induced host protection further confirming the essential role of Th17 along with Th1 cytokines in host protection. Treatment with recombinant IL-23, which is required for stabilization and maintenance of IL-17, heightened Th17, and Tc17 responses in immunized mice splenocytes. In contrast, Th17 response was absent in immunized IL-23R mice that failed to induce protection upon virulent challenge suggesting that IL-23 plays an essential role in IL-17-mediated protection by parasites. This study unveiled the role of IL-23-dependent IL-17 induction in parasite-induced immunity and subsequent protection against visceral leishmaniasis.
[Mh] Termos MeSH primário: Interleucina-17/metabolismo
Interleucina-23/metabolismo
Leishmania donovani/imunologia
Vacinas contra Leishmaniose/imunologia
Leishmaniose Visceral/imunologia
Células Th1/imunologia
Células Th17/imunologia
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Feminino
Seres Humanos
Leishmania donovani/genética
Vacinas contra Leishmaniose/genética
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Proteínas de Protozoários/genética
Receptores de Interleucina/genética
Células Th1/parasitologia
Células Th17/parasitologia
Vacinas Atenuadas/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nome de substância:
0 (Interleukin-17); 0 (Interleukin-23); 0 (Leishmaniasis Vaccines); 0 (Protozoan Proteins); 0 (Receptors, Interleukin); 0 (Vaccines, Attenuated); 0 (interleukin-23 receptor, mouse)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180131
[Lr] Data última revisão:
180131
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1700674


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[PMID]:29278948
[Au] Autor:Nocentini A; Cadoni R; Dumy P; Supuran CT; Winum JY
[Ad] Endereço:a Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS, ENSCM, Université de Montpellier , Montpellier Cedex , France.
[Ti] Título:Carbonic anhydrases from Trypanosoma cruzi and Leishmania donovani chagasi are inhibited by benzoxaboroles.
[So] Source:J Enzyme Inhib Med Chem;33(1):286-289, 2018 Dec.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A series of 6-substituted ureido- and thioureido-benzoxaboroles were investigated as inhibitors of carbonic anhydrases from Trypanosoma cruzi (TcCA), and Leishmania donovani chagasi (LdcCA). Both enzymes were inhibited by benzoxaboroles in the micromolar range. Preferential inhibitory potency against the ß-CA LdcCA versus the α-CA TcCA was observed with submicromolar inhibitory activities. Some derivatives displayed excellent inhibitory and selectivity profile over the ubiquitous and physiological relevant human off-target hCA II. This study provides a convincing opportunity to study benzoxaborole scaffold for the design of antiprotozoan potential drugs targeting the pathogen's carbonic anhydrases.
[Mh] Termos MeSH primário: Antiprotozoários/farmacologia
Compostos de Boro/farmacologia
Inibidores da Anidrase Carbônica/farmacologia
Anidrases Carbônicas/metabolismo
Compostos Heterocíclicos com 2 Anéis/farmacologia
Leishmania donovani/efeitos dos fármacos
Trypanosoma cruzi/efeitos dos fármacos
[Mh] Termos MeSH secundário: Antiprotozoários/síntese química
Antiprotozoários/química
Compostos de Boro/síntese química
Compostos de Boro/química
Inibidores da Anidrase Carbônica/síntese química
Inibidores da Anidrase Carbônica/química
Relação Dose-Resposta a Droga
Compostos Heterocíclicos com 2 Anéis/síntese química
Compostos Heterocíclicos com 2 Anéis/química
Leishmania donovani/enzimologia
Testes de Sensibilidade Microbiana
Estrutura Molecular
Relação Estrutura-Atividade
Trypanosoma cruzi/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiprotozoal Agents); 0 (Boron Compounds); 0 (Carbonic Anhydrase Inhibitors); 0 (Heterocyclic Compounds, 2-Ring); EC 4.2.1.1 (Carbonic Anhydrases)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.1080/14756366.2017.1414808


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[PMID]:29240765
[Au] Autor:Ponte-Sucre A; Gamarro F; Dujardin JC; Barrett MP; López-Vélez R; García-Hernández R; Pountain AW; Mwenechanya R; Papadopoulou B
[Ad] Endereço:Department of Physiological Sciences, Laboratory of Molecular Physiology, Institute of Experimental Medicine, Luis Razetti School of Medicine, Universidad Central de Venezuela, Caracas, Venezuela.
[Ti] Título:Drug resistance and treatment failure in leishmaniasis: A 21st century challenge.
[So] Source:PLoS Negl Trop Dis;11(12):e0006052, 2017 Dec.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Reevaluation of treatment guidelines for Old and New World leishmaniasis is urgently needed on a global basis because treatment failure is an increasing problem. Drug resistance is a fundamental determinant of treatment failure, although other factors also contribute to this phenomenon, including the global HIV/AIDS epidemic with its accompanying impact on the immune system. Pentavalent antimonials have been used successfully worldwide for the treatment of leishmaniasis since the first half of the 20th century, but the last 10 to 20 years have witnessed an increase in clinical resistance, e.g., in North Bihar in India. In this review, we discuss the meaning of "resistance" related to leishmaniasis and discuss its molecular epidemiology, particularly for Leishmania donovani that causes visceral leishmaniasis. We also discuss how resistance can affect drug combination therapies. Molecular mechanisms known to contribute to resistance to antimonials, amphotericin B, and miltefosine are also outlined.
[Mh] Termos MeSH primário: Resistência a Medicamentos
Leishmania/efeitos dos fármacos
Leishmania/patogenicidade
Leishmaniose/tratamento farmacológico
[Mh] Termos MeSH secundário: Anfotericina B/farmacologia
Anfotericina B/uso terapêutico
Antiprotozoários/farmacologia
Antiprotozoários/uso terapêutico
Quimioterapia Combinada
Seres Humanos
Leishmania/genética
Leishmania donovani/efeitos dos fármacos
Leishmania donovani/patogenicidade
Leishmaniose/imunologia
Leishmaniose/parasitologia
Leishmaniose Cutânea/tratamento farmacológico
Leishmaniose Visceral/tratamento farmacológico
Leishmaniose Visceral/parasitologia
Epidemiologia Molecular
Fosforilcolina/análogos & derivados
Fosforilcolina/farmacologia
Fosforilcolina/uso terapêutico
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antiprotozoal Agents); 107-73-3 (Phosphorylcholine); 53EY29W7EC (miltefosine); 7XU7A7DROE (Amphotericin B)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171224
[Lr] Data última revisão:
171224
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006052


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[PMID]:29176865
[Au] Autor:Cecílio P; Pérez-Cabezas B; Fernández L; Moreno J; Carrillo E; Requena JM; Fichera E; Reed SG; Coler RN; Kamhawi S; Oliveira F; Valenzuela JG; Gradoni L; Glueck R; Gupta G; Cordeiro-da-Silva A
[Ad] Endereço:Parasite Disease group, Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.
[Ti] Título:Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis.
[So] Source:PLoS Negl Trop Dis;11(11):e0005951, 2017 Nov.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The notion that previous infection by Leishmania spp. in endemic areas leads to robust anti-Leishmania immunity, supports vaccination as a potentially effective approach to prevent disease development. Nevertheless, to date there is no vaccine available for human leishmaniasis. We optimized and assessed in vivo the safety and immunogenicity of an innovative vaccine candidate against human visceral leishmaniasis (VL), consisting of Virus-Like Particles (VLP) loaded with three different recombinant proteins (LJL143 from Lutzomyia longipalpis saliva as the vector-derived (VD) component, and KMP11 and LeishF3+, as parasite-derived (PD) antigens) and adjuvanted with GLA-SE, a TLR4 agonist. No apparent adverse reactions were observed during the experimental time-frame, which together with the normal hematological parameters detected seems to point to the safety of the formulation. Furthermore, measurements of antigen-specific cellular and humoral responses, generally higher in immunized versus control groups, confirmed the immunogenicity of the vaccine formulation. Interestingly, the immune responses against the VD protein were reproducibly more robust than those elicited against leishmanial antigens, and were apparently not caused by immunodominance of the VD antigen. Remarkably, priming with the VD protein alone and boosting with the complete vaccine candidate contributed towards an increase of the immune responses to the PD antigens, assessed in the form of increased ex vivo CD4+ and CD8+ T cell proliferation against both the PD antigens and total Leishmania antigen (TLA). Overall, our immunogenicity data indicate that this innovative vaccine formulation represents a promising anti-Leishmania vaccine whose efficacy deserves to be tested in the context of the "natural infection".
[Mh] Termos MeSH primário: Anticorpos Antiprotozoários/sangue
Antígenos de Protozoários/imunologia
Imunogenicidade da Vacina
Vacinas contra Leishmaniose/imunologia
Leishmaniose Visceral/prevenção & controle
Saliva/imunologia
[Mh] Termos MeSH secundário: Adjuvantes Imunológicos/administração & dosagem
Animais
Seres Humanos
Imunidade Celular
Imunidade Humoral
Leishmania donovani
Leishmaniose Visceral/imunologia
Ativação Linfocitária
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Psychodidae/imunologia
Psychodidae/parasitologia
Proteínas Recombinantes/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Antibodies, Protozoan); 0 (Antigens, Protozoan); 0 (Leishmaniasis Vaccines); 0 (Recombinant Proteins)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005951


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[PMID]:28958943
[Au] Autor:Reddy GS; Mukhopadhyay AG; Dey CS
[Ad] Endereço:Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India.
[Ti] Título:The p38 MAP kinase inhibitor, PD 169316, inhibits flagellar motility in Leishmania donovani.
[So] Source:Biochem Biophys Res Commun;493(4):1425-1429, 2017 Dec 02.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mitogen-activated protein kinases (MAPKs) have been demonstrated to regulate flagellar/ciliary motility of spermatozoa and miracidia of Schistosoma mansoni. However, the role of MAPKs in mediating flagella-driven motility of Leishmania donovani is unexplored. We investigated the function of MAPKs in motility regulation of L. donovani using pharmacological inhibitors and activators of various MAPKs and fast-capture videomicroscopy. Our studies have revealed that the inhibitor of p38 MAPK, PD 169316, significantly affected various motility parameters such as flagellar beat frequency, parasite swimming speed, waveform of the flagellum and resulted in reduced parasite motility. Together, our results suggest that a MAPK, similar to human p38 MAPK, is implicated in flagellar motility regulation of L. donovani.
[Mh] Termos MeSH primário: Flagelos/efeitos dos fármacos
Imidazóis/farmacologia
Leishmania donovani/efeitos dos fármacos
Leishmania donovani/fisiologia
Inibidores de Proteínas Quinases/farmacologia
Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Anisomicina/farmacologia
Antracenos/farmacologia
Flagelos/fisiologia
Flavonoides/farmacologia
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Sistema de Sinalização das MAP Quinases/fisiologia
Microscopia de Vídeo
Movimento/efeitos dos fármacos
Movimento/fisiologia
Proteínas de Protozoários/antagonistas & inibidores
Proteínas de Protozoários/fisiologia
Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one); 0 (Anthracenes); 0 (Flavonoids); 0 (Imidazoles); 0 (Protein Kinase Inhibitors); 0 (Protozoan Proteins); 1TW30Y2766 (pyrazolanthrone); 6C74YM2NGI (Anisomycin); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); GX3Y2V80CV (2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170930
[St] Status:MEDLINE


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[PMID]:28957391
[Au] Autor:Hossain F; Ghosh P; Khan MAA; Duthie MS; Vallur AC; Picone A; Howard RF; Reed SG; Mondal D
[Ad] Endereço:Laboratory of Emerging Infections and Parasitology, Nutrition and Clinical science division, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
[Ti] Título:Real-time PCR in detection and quantitation of Leishmania donovani for the diagnosis of Visceral Leishmaniasis patients and the monitoring of their response to treatment.
[So] Source:PLoS One;12(9):e0185606, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sustained elimination of Visceral Leishmaniasis (VL) requires the reduction and control of parasite reservoirs to minimize the transmission of Leishmania donovani infection. A simple, reproducible and definitive diagnostic procedure is therefore indispensable for the early and accurate detection of parasites in VL, Relapsed VL (RVL) and Post Kala-azar Dermal Leishmaniasis (PKDL) patients, all of whom are potential reservoirs of Leishmania parasites. To overcome the limitations of current diagnostic approaches, a novel quantitative real-time polymerase chain reaction (qPCR) method based on Taqman chemistry was devised for the detection and quantification of L. donovani in blood and skin. The diagnostic efficacy was evaluated using archived peripheral blood buffy coat DNA from 40 VL, 40 PKDL, 10 RVL, 20 cured VL, and 40 cured PKDL along with 10 tuberculosis (TB) cases and 80 healthy endemic controls. Results were compared to those obtained using a Leishmania-specific nested PCR (Ln-PCR). The real time PCR assay was 100% (95% CI, 91.19-100%) sensitive in detecting parasite genomes in VL and RVL samples and 85.0% (95% CI, 70.16-94.29%) sensitive for PKDL samples. In contrast, the sensitivity of Ln-PCR was 77.5% (95% CI, 61.55-89.16%) for VL samples, 100% (95%CI, 69.15-100%) for RVL samples, and 52.5% (95% CI, 36.13-68.49%) for PKDL samples. There was significant discordance between the two methods with the overall sensitivity of the qPCR assay being considerably higher than Ln-PCR. None of the assay detected L. donovani DNA in buffy coats from cured VL cases, and reduced infectious burdens were demonstrated in cured PKDL cases who remained positive in 7.5% (3/40) and 2.5% (1/40) cases by real-time PCR and Ln-PCR, respectively. Both assays were 100% (95% CI, 95.98-100) specific with no positive signals in either endemic healthy control or TB samples. The real time PCR assay we developed offers a molecular tool for accurate detection of circulating L. donovani parasites in VL, PKDL and RVL patients, as well as being capable of assessing response to treatment. As such, this real time PCR assay represents an important contribution in efforts to eliminate VL.
[Mh] Termos MeSH primário: DNA de Protozoário/metabolismo
Leishmania donovani/genética
Leishmaniose Visceral/diagnóstico
Monitorização Fisiológica/métodos
Reação em Cadeia da Polimerase em Tempo Real/métodos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Estudos de Casos e Controles
Criança
Feminino
Seres Humanos
Leishmaniose Visceral/tratamento farmacológico
Masculino
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Protozoan)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170929
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185606


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[PMID]:28945751
[Au] Autor:Melo GD; Goyard S; Lecoeur H; Rouault E; Pescher P; Fiette L; Boissonnas A; Minoprio P; Lang T
[Ad] Endereço:Institut Pasteur, Laboratoire des Processus Infectieux à Trypanosomatidés, Département Infection et Epidémiologie, 25-28 rue du Dr Roux, Paris, France.
[Ti] Título:New insights into experimental visceral leishmaniasis: Real-time in vivo imaging of Leishmania donovani virulence.
[So] Source:PLoS Negl Trop Dis;11(9):e0005924, 2017 Sep.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:TRIAL REGISTRATION: ClinicalTrials.gov 2013-0047.
[Mh] Termos MeSH primário: Leishmania donovani/patogenicidade
Leishmaniose Visceral/diagnóstico por imagem
Leishmaniose Visceral/parasitologia
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Seres Humanos
Leishmania donovani/genética
Luciferases
Medições Luminescentes
Mesocricetus
Camundongos
Camundongos Endogâmicos BALB C
Inoculações Seriadas
Transfecção
Virulência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 1.13.12.- (Luciferases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170926
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005924



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