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1.
An. bras. dermatol ; 96(5): 602-604, Sept.-Oct. 2021. graf
Article in English | LILACS | ID: biblio-1345132

ABSTRACT

Abstract Diffuse cutaneous leishmaniasis is a rare universal disease associated with an inadequate host cell immune response, caused by different species: infantum, aethiopica, major, mexicana, and others, which presents the challenge of a poor therapeutic response. In Brazil, it is caused by L. amazonensis. A case confirmed by histopathology with an abundance of vacuolated macrophages full of amastigotes and lymphocyte scarcity, identified by RFLP-ITS1PCR and in vitro decrease and exhaustion of the host cell immune response to L. amazonensis antigen, was treated early (3 months after the onset) with Glucantime (2 months) and allopurinol (29 months) with clinical cure, after a follow-up for 30 months after treatment.


Subject(s)
Humans , Leishmania mexicana , Leishmaniasis, Diffuse Cutaneous/drug therapy , Leishmaniasis, Cutaneous/drug therapy , Antiprotozoal Agents/therapeutic use , Brazil , Meglumine Antimoniate
2.
Rev. Soc. Bras. Med. Trop ; 54: e0305-2020, 2021. graf
Article in English | LILACS | ID: biblio-1155563

ABSTRACT

Abstract Cutaneous leishmaniasis (CL) involves several differential diagnoses as it lacks a gold standard diagnostic test. Its diagnosis is easier in endemic regions; however, many cases come from travelers to endemic areas. A 22-year-old patient, who had recently visited Oaxaca, Mexico, developed two asymptomatic ulcers weeks later on the left auricle and the nose. Leishmania mexicana was identified using polymerase chain reaction. The patient was treated with imiquimod 5% cream three times/week, providing favorable results after 12 weeks, without relapse 2 months after therapy. To our knowledge, this is the first case of CL due to L. mexicana effectively treated with imiquimod.


Subject(s)
Humans , Young Adult , Leishmania mexicana , Leishmaniasis, Mucocutaneous , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Cutaneous/drug therapy , Imiquimod , Mexico
3.
Rio de Janeiro; s.n; ilus; 2020. 173 p. ilus.
Thesis in Portuguese | LILACS | ID: biblio-1252813

ABSTRACT

As leishmanioses são causadas por cerca de 20 espécies de Leishmania e se apresentam em diversas formas clínicas, que podem variar de branda a muito grave. Elas afetam milhões de pessoas e até então não existem medidas de controle eficazes. Assim, a imunização da população seria uma alternativa eficiente de controle. Evidências sugerem que a resposta imune que se estabelece após a cura clínica de leishmanioses deva constituir um padrão de resposta imunológica associado à proteção, e que uma preparação vacinal deveria estimulá-la preferencialmente. Nosso grupo demonstrou que antígenos de L. (Viannia) naiffi (espécie considerada benigna) conseguem induzir respostas bem moduladas, e que soros de voluntários curados de leishmaniose tegumentar cutânea reconheceram frações desse antígeno consideradas imunodominantes. Experimentos anteriores demonstraram em hamster que a imunização intranasal com antígenos totais dessa espécie são capazes de induzir uma imunidade protetora contra L. (V.) braziliensis. O mesmo grupo já havia obtido a mesma resposta protetora utilizando o antígeno total de L. (L.) amazonensis. No entanto, sabe-se que nem todos os componentes presentes nesses antígenos estão associados à proteção e que a identificação de proteínas que sejam imunogênicas é uma etapa indispensável na formulação de uma vacina.


O objetivo deste trabalho foi identificar as proteínas imunodominantes presentes nas frações solúveis de L. (L.) amazonensis (LaAg(s)) e L.(V.) naiffi (LnAg(s)), que sejam conservadas dentro do gênero Leishmania, para formular uma vacina pan específica para o controle das leishmanioses. Primeiramente, os antígenos LnAg(s) e LaAg(s) foram subfracionados em gel de poliacrilamida e as bandas com peso molecular entre 35 e 100KDa foram extraídas e submetidas à análise por espectrometria de massa para análise proteômica. Desta análise, foram obtidas as sequências de aminoácidos, o tamanho das sequências, e a abundância das proteínas. As proteínas mais abundantes foram submetidas à análise de similaridade com proteínas de hospedeiros. As proteínas de LnAg(s) e LaAg(s) com baixa similaridade (<30%) às proteínas humanas foram analisadas por preditores de epítopos reconhecidos por linfócitos B.


Em paralelo, a predição de epítopos presentes em LnAg(s) e LaAg(s), capazes de se ligar com alta afinidade a moléculas HLA classes I e II, assim como a promiscuidade de ligação a alelos de HLA para cada proteína, foram avaliados dentre aquelas que apresentaram maior abundância e baixa similaridade. Por fim, após a análise de homologia das proteínas entre as espécies de Leishmania, foram identificadas 11 proteínas com mais homólogos. Elas apresentaram potencial de reconhecimento por linfócitos B, assim como também por componentes da resposta imune celular (como predito para a apresentação por HLA classes I e II). O potencial de ativação de linfócitos T pelos epítopos presentes nas 11 proteínas foi incrementado pela ampla capacidade de apresentação antigênica na população humana, devido à alta promiscuidade quanto à capacidade de ligação destes epítopos a alelos de HLA. Esses resultados contribuem para a identificação de antígenos com potencial de compor um protótipo vacinal capaz de induzir uma resposta imune protetora pan específica em humanos, com características imunodominantes e indutoras de resposta humoral e celular, para serem empregados no controle das leishmanioses. (AU)


Subject(s)
Humans , Leishmania mexicana , Lymphocyte Activation , Leishmaniasis , Immunization , Epitopes, T-Lymphocyte
4.
Rev. Soc. Bras. Med. Trop ; 53: e20200091, 2020. graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS, SES-SP | ID: biblio-1136875

ABSTRACT

Abstract INTRODUCTION: The drugs currently available for leishmaniasis treatment have major limitations. METHODS: In vitro and in vivo studies were performed to evaluate the effect of a quinoline derivative, Hydraqui (7-chloro-4-(3-hydroxy-benzilidenehydrazo)quinoline, against Leishmania amazonensis. In silico analyses of absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters were performed. RESULTS: Hydraqui showed significant in vitro anti-amastigote activity. Also, Hydraqui-treated mice exhibited high efficacy in lesion size (48.3%) and parasitic load (93.8%) reduction, did not cause hepatic and renal toxicity, and showed appropriate ADMET properties. CONCLUSIONS: Hydraqui presents a set of satisfactory criteria for its application as an antileishmanial agent.


Subject(s)
Animals , Female , Quinolines/therapeutic use , Leishmania mexicana/drug effects , Leishmaniasis, Cutaneous/drug therapy , Antiprotozoal Agents/therapeutic use , Quinolines/chemistry , Leishmaniasis, Cutaneous/parasitology , Disease Models, Animal , Parasite Load , Mice , Mice, Inbred BALB C
5.
Mem. Inst. Oswaldo Cruz ; 114: e180482, 2019. graf
Article in English | LILACS | ID: biblio-1040621

ABSTRACT

The leishmaniases are caused by Leishmania parasites and transmitted through the bites of phlebotomine sand flies. During parasite development inside the vector's midgut, promastigotes move towards the stomodeal valve, a mechanism that is crucial for transmission. It has been reported that the sugar meal acquired by sand flies during feeding between bloodmeals is essential for the development and migration of parasites. We demonstrated that the distribution of Leishmania mexicana parasites was affected by the sugar meals obtained by the sand flies. Promastigote migration towards the cardia region seems to be only partially based on the stimuli provided by sugar molecules. In the absence of sugars, significant amounts of parasites developed in the hindgut. In addition, sugar meals were important for the survival of sand flies, especially during blood digestion, presumably supporting their energy requirements.


Subject(s)
Animals , Female , Psychodidae/parasitology , Leishmania mexicana/physiology , Gastrointestinal Tract/parasitology , Sugars/metabolism , Feeding Behavior/physiology , Insect Vectors/parasitology , Psychodidae/physiology , Leishmania mexicana/growth & development , Insect Vectors/physiology , Longevity
6.
Rev. patol. trop ; 48(2): 99-108, 2019.
Article in English | LILACS | ID: biblio-1025792

ABSTRACT

The cell culture insert system is a culturing system for the study of contact-independent cellular communication. Leishmaniasis is a neglect tropical disease with no vaccines and the available drugs present toxic side effects. Studies on Leishmania interaction with host macrophages aim to develop strategies for parasite control and drug development. The purpose of this study was to evaluate the effects of interaction between non-infected and L. amazonensis-infected human macrophages, by using the cell culture system. The results showed that the infection index was reduced by 56.2% as compared to controls only when infected macrophages were inserted on both sides of the Transwell membranes. An improvement in macrophage viability was also observed in this cell culture. The levels of interleukin-1ß, an inflammatory cytokine, and nitric oxide, a microbicidal molecule, did not increase in L. amazonensis-infected macrophage cultures in the Transwell system; thus other soluble factors were responsible for parasite control


Subject(s)
Leishmania mexicana , Leishmaniasis , Primary Cell Culture , Macrophages
7.
Mem. Inst. Oswaldo Cruz ; 113(4): e170345, 2018. graf
Article in English | LILACS | ID: biblio-894915

ABSTRACT

BACKGROUND Leishmaniasis, one of the most neglected diseases, is a serious public health problem in many countries, including Brazil. Currently available treatments require long-term use and have serious side effects, necessitating the development of new therapeutic interventions. Because translocator protein (TSPO) levels are reduced in Leishmania amazonensis-infected cells and because this protein participates in apoptosis and immunomodulation, TSPO represents a potential target for Leishmania chemotherapy. The present study evaluated PK11195, a ligand of this protein, as an anti-leishmanial agent. OBJECTIVE To evaluate the leishmanicidal activity of PK11195 against L. amazonensis in infected CBA mouse macrophages in vitro. METHODS The viability of axenic L. amazonensis, Leishmania major, and Leishmania braziliensis promastigotes was assessed after 48 h treatment with PK11195 (0.2-400 µM). Additionally, intracellular parasite viability was evaluated to determine IC50 values and the number of viable parasites in infected macrophages treated with PK11195 (50-100 µM). Infected macrophages were then treated with PK11195 (25-100 µM) to determine the percentage of L. amazonensis-infected cells and the number of parasites per infected cell. Electron microscopy was used to investigate morphological changes caused by PK11195. The production of free oxygen radicals, nitric oxide, and pro-inflammatory cytokines was also evaluated in infected macrophages treated with PK11195 and primed or not primed with IFN-γ. FINDINGS Median IC50 values for PK11195 were 14.2 µM for L. amazonensis, 8.2 µM for L. major, and 3.5 µM for L. braziliensis. The selective index value for L. amazonensis was 13.7, indicating the safety of PK11195 for future testing in mammals. Time- and dose-dependent reductions in the percentage of infected macrophages, the number of parasites per infected macrophage, and the number of viable intracellular parasites were observed. Electron microscopy revealed some morphological alterations suggestive of autophagy. Interestingly, MCP-1 and superoxide levels were reduced in L. amazonensis-infected macrophages treated with PK11195. MAIN CONCLUSIONS PK11195 causes the killing of amastigotes in vitro by mechanisms independent of inflammatory mediators and causes morphological alterations within Leishmania parasites, suggestive of autophagy, at doses that are non-toxic to macrophages. Thus, this molecule has demonstrated potential as an anti-leishmanial agent.


Subject(s)
Humans , Leishmania mexicana , Drug Utilization , Macrophages
8.
Rio de Janeiro; s.n; 2018. xiii, 218 p. ilus.
Thesis in Portuguese | LILACS | ID: biblio-1025747

ABSTRACT

Lutzomyia longipalpis é o vetor de Leishmania infantum, um dos agentes causadores da leishmaniose visceral. Os flebotomíneos adultos possuem uma dieta rica em açúcares, essencial para atender às demandas energéticas necessárias ao desenvolvimento; as fêmeas, além de açúcares, também se alimentam de sangue. As α-glicosidases e α-amilases estão envolvidas na digestão de carboidratos adquiridos na dieta, e são classificadas nas famílias 13 e 31 das glicosídeo hidrolases. Para determinação da atividade de α-glicosidase utilizando o substrato MUαGlu padronizamos uma técnica de ensaio contínuo para realização de ensaios em amostras teciduais individuais. Quantificamos a atividade de α-glicosidase em diferentes tecidos, ressaltando a atividade presente no divertículo e no intestino médio de L. longipalpis, sendo essa enzima mais ativa sobre sacarose que sobre o substrato MUαGlu. Atividades basais foram observadas em insetos não alimentados; a alimentação sanguínea induz a atividade no conteúdo do intestino médio e a alimentação açucarada modula a atividade nos tecidos do intestino médio. A exposição a diferentes concentrações ou moléculas de açúcares também alterou a atividade. As α-glicosidases de diferentes tecidos apresentaram diferentes propriedades bioquímicas, como pH ótimo entre 7,0 - 8,0, KM entre 0,37 - 4,7 mM (MUαGlu como substrato), pH ótimo de 6,0 e KM entre 11 - 800 mM (sacarose como substrato)


Enzimas do divertículo e do tecido do intestino médio apresentaram inibição em altas concentrações de substrato (sacarose), o que explica os altos valores de KM encontrados. No genoma de L. longipalpis foram encontradas nas famílias GH13 e GH31 proteinas envolvidas no metabolismo de açúcar, transporte de aminoácidos, armazenamento e mobilização das reservas de glicogênio e regulação da miogênese. Descrevemos também uma α-glicosidase neutra (controle de N-glicosilação) e uma α-glicosidase lisossomal inativa (sem resíduos catalícos). A estrutura e as funções dessas proteínas identificadas são conservadas. Uma análise comparativa demonstrou retração no número de genes de maltases e expansão das α-amilases, com organização em dois grandes clusters. Maltases são mais expressas no intestino médio de fêmeas alimentadas com sangue, e a infecção por L. mexicana modulou negativamente a sua expressão gênica. Em fêmeas alimentadas com sangue (sem sacarose), as taxas de infecção por L. mexicana e migração para a região da cárdia não foram afetadas, sugerindo que a migração não é inteiramente baseada nos estímulos de quimiotaxia pelas moléculas de açúcar. Contudo, a ausência de açúcar na dieta do inseto resultou no desenvolvimento de L. mexicana no intestino posterior. Todos esses resultados sugerem que as α-amilases evoluíram para assumir diferentes funções além da hidrólise de açúcares primários e que as α-glicosidases também estão envolvidas em diferentes processos metabólicos, como digestão de açúcares vegetais, digestão de glicoproteínas ou glicolipídios sanguíneos e mobilização de estoques energéticos. (AU)


Subject(s)
Animals , Psychodidae , Leishmania mexicana , Digestion , alpha-Glucosidases
9.
Mem. Inst. Oswaldo Cruz ; 112(2): 146-154, Feb. 2017. graf
Article in English | LILACS | ID: biblio-841766

ABSTRACT

BACKGROUND Leishmaniasis is a parasitosis caused by several species of the genus Leishmania. These parasites present high resistance against oxidative stress generated by inflammatory cells. OBJECTIVES To investigate oxidative stress and molecular inflammatory markers in BALB/c mice infected with L. amazonensis and the effect of antioxidant treatment on these parameters. METHODS Four months after infection, oxidative and inflammatory parameters of liver, kidneys, spleen, heart and lungs from BALB/c mice were assessed. FINDINGS In liver, L. amazonensis caused thiol oxidation and nitrotyrosine formation; SOD activity and SOD2 protein content were increased while SOD1 protein content decreased. The content of the cytokines IL-1β, IL-6, TNF-α, and the receptor of advanced glycation endproducts (RAGE) increased in liver. Treatment with the antioxidant N-acetyl-cysteine (20 mg/kg b.w) for five days inhibited oxidative stress parameters. MAIN CONCLUSIONS L. amazonensis induces significant alterations in the redox status of liver but not in other organs. Acute antioxidant treatment alleviates oxidative stress in liver, but it had no effect on pro-inflammatory markers. These results indicate that the pathobiology of leishmaniasis is not restricted to the cutaneous manifestations and open perspectives for the development of new therapeutic approaches to the disease, especially for liver function.


Subject(s)
Animals , Mice , Acetylcysteine/pharmacology , Leishmania mexicana , Leishmaniasis, Cutaneous/metabolism , Leishmaniasis, Cutaneous/pathology , Oxidative Stress/drug effects , Oxidative Stress/physiology , Free Radical Scavengers/pharmacology , Liver/drug effects , Liver/enzymology , Mice, Inbred BALB C
10.
Mem. Inst. Oswaldo Cruz ; 112(1): 44-52, Jan. 2017. tab, graf
Article in English | LILACS | ID: biblio-841754

ABSTRACT

Leishmania are protozoan parasites that show remarkable diversity, as revealed by the various clinical forms of leishmaniasis, which can range from mild skin lesions to severe metastatic cutaneous/mucosal lesions. The exact nature and extent of Leishmania phenotypic diversity in establishing infection is not fully understood. In order to try to understand some aspects of this diversity, we subcutaneously infected BALB/c mice with first and second generation subclones of a L. amazonensis strain isolated from a patient (BA125) and examined in vivo lesion growth rate and antimony susceptibility. In vivo fast-, medium- and slow-growing subclones were obtained; moreover, fast-growing subclones could generate slow-growing subclones and inversely, revealing the continuous generation of diversity after passage into mice. No antimony-resistant subclone appeared, probably a rare occurrence. By tagging subclone cells with a L. amazonensis genomic cosmid library, we found that only a very small number of founding cells could produce lesions. Leishmania clones transfected with in vivo selected individual cosmids were also diverse in terms of lesion growth rate, revealing the cosmid-independent intrinsic characteristics of each clone. Our results suggest that only a few of the infecting parasites are able to grow and produce lesions; later, within the cell mixture of each lesion, there coexist several parasite populations with different potentialities to grow lesions during the next infection round. This may reflect a sort of programmed heterogeneity of individual parasites, favoring the survival of some individuals in various environmental conditions.


Subject(s)
Animals , Female , Leishmania mexicana/genetics , Leishmania mexicana/pathogenicity , Leishmaniasis, Cutaneous/parasitology , Disease Models, Animal , Phenotype , Time Factors , Mice, Inbred BALB C
11.
Journal of Lasers in Medical Sciences. 2017; 8 (1): 46-50
in English | IMEMR | ID: emr-187547

ABSTRACT

Introduction: The treatment of cutaneous leishmaniasis [CL] is based primarily on the use of pentavalent antimonials, which may lead to many side effects limiting their use. Photodynamic therapy [PDT] is an alternative for the treatment of CL, and some xanthene dyes have the potential for use in PDT


Methods: The xanthenes rose bengal B [RB] and its derivatives rose bengal methyl ester [RBMET], and butyl ester [RBBUT] were analyzed for leishmanicidal activity against promastigotes and intracellular amastigotes of Leishmania amazonensis. Cytotoxicity was assessed in J774.A1 macrophages


Results: RB derivates RBMET [IC50 9.83 microM], and RBBUT [IC50 45.08 microM] showed leishmanicidal activity, however, were toxic to J774.A1 macrophages, resulting in low selectivity index


Conclusion: The RBMET and RBBUT showed to be effective against the L. amazonensis and the low selectivity index presented may not be a limitation for their use in PDT to CL treatment


Subject(s)
Photochemotherapy , Leishmania mexicana/drug effects , Leishmania mexicana/radiation effects , Rose Bengal/analogs & derivatives , Xanthenes/pharmacology
12.
Braz. J. Pharm. Sci. (Online) ; 53(1): e16067, 2017. tab, graf
Article in English | LILACS | ID: biblio-839450

ABSTRACT

ABSTRACT We describe herein the synthesis and evaluation of the antileishmanial activity against promastigote forms of Leishmania amazonensis and cytotoxicity to murine macrophages of a series of 2-chloro-N-arylacetamide derivatives. All compounds were active, except one (compound 3). Compound 5 presented the most promising results, showing good antileishmanial activity (CI50=5.39±0.67 µM) and moderate selectivity (SI=6.36), indicating that further development of this class is worthwhile. Preliminary QSAR studies, although not predictive, furnished some insights on the importance of electronic character of aryl substituent to biological activity, as well as an indirect influence of hydrophobicity on activity.


Subject(s)
Animals , Female , Rats , Leishmaniasis/drug therapy , Quantitative Structure-Activity Relationship , Leishmania mexicana/isolation & purification , Hydrophobic and Hydrophilic Interactions , Macrophages/cytology
13.
Salvador; s.n; 2017. 77 p. ilus, map.
Thesis in Portuguese | LILACS | ID: biblio-1001004

ABSTRACT

A Leishmaniose Cutânea Difusa (LCD) é uma manifestação clínica. rara causada pela Leishmania amazonensis que é caracterizada por uma resposta celular. parasitária ineficiente e macrófagos intensamente parasitados nas lesões cutâneas.. Mediadores lipídicos e seus precursores desempenham um papel crucial durante a. infecção por Leishmania. Estudos prévios demonstram que pacientes com leishmaniose. tegumentar, exibem um distinto balanço de eicosanoides in situ e sistêmico.. Recentemente, demonstrou-se que mediadores lipídicos especializados na pró-resolução. desempenham um papel crítico na redução de processos inflamatórios patológicos. induzindo a restauração da homeostasia em diferentes modelos experimentais. Entre. esses mediadores, as resolvinas da série D exibem potente atividade anti-inflamatória e. imuno-regulatória que inclui a inibição da quimiotaxia leucocitária e bloqueio na. produção de citocinas pró-inflamatórias. No entanto, ainda é desconhecido se as. resolvinas desempenham um papel significativo no estabelecimento e persistência da. infecção por Leishmania. OBJETIVO: Nesse estudo, avaliamos os níveis circulantes. de Resolvina D1 (RvD1) em pacientes com leishmaniose tegumentar apresentando a. forma clínica cutânea localizada (LCL) ou difusa. RESULTADOS: Nossos resultados. demonstram que pacientes com LCD apresentam maiores níveis plasmáticos de RvD1. quando comparados a LCL ou controles endêmicos. Além disso, os níveis séricos de. RvD1 em pacientes com LCD se correlacionam positivamente com a Arginase I e TGF-. β, enquanto que inversamente com os níveis sistêmicos de TNF-α. Experimentos. adicionais in vitro utilizando macrófagos humanos revelaram que a RvD1 promove a. replicação intracelular da L. amazonensis por um mecanismo associado a indução da. enzima heme oxigenase-1. CONCLUSÃO: Os resultados sugerem que a via de. produção da RvD1 pode servir como uma potencial estratégia terapêutica para os. pacientes com LCD.


INTRODUCTION: Diffuse Cutaneous Leishmaniasis (DCL) is a rare clinical manifestation caused by Leishmania amazonensis that is characterized by an inefficient parasite-specific cellular responses and heavily parasitized macrophages in skin lesions. Lipid mediators and their precursors play a crucial role during Leishmania infection. Previous works have shown that patients with cutaneous leishmaniasis exhibit a distinct in situ and systemic balance of this eicosanoids. Recently, pro-resolution lipid mediators have been shown to play critical role in dampening pathological inflammatory processes to reestablish homeostasis in a diverse range of experimental settings. Among these mediators, resolvins from D series have been described to exhibit potent antiinflammatory and immune-regulatory activities that include inhibition of leukocyte chemotaxis and blockage on the production of proinflammatory cytokines. However, whether resolvins play significant roles in establishment and persistence of Leishmania infection is currently unknown. AIM: We addressed this question by assessing circulating levels of resolvin D1 (RvD1) in tegumentary leishmaniasis patients presenting localized cutaneous leishmaniasis (LCL) or diffuse disease. RESULTS: We found that DCL patients have higher plasma levels of RvD1 when compared with LCL patients or endemic controls. In addition, the levels of this mediator were positively correlated with arginase-I and TGF-β and were negatively correlated with TNF-α levels. Additional in vitro experiments using primary human macrophages revealed that resolvin D1 promotes the intracellular L. amazonensis replication for a mechanism dependent on induction of heme oxygenase-1 enzyme. CONCLUSION: These results indicate that targeting RvD1 could serve as potential strategy for DCL patients.


Subject(s)
Humans , Leishmania mexicana/pathogenicity , Leishmaniasis, Diffuse Cutaneous/diagnosis , Leishmaniasis, Diffuse Cutaneous/immunology , Leishmaniasis, Diffuse Cutaneous/parasitology , Leishmaniasis, Diffuse Cutaneous/pathology , Leishmaniasis, Diffuse Cutaneous/prevention & control , Leishmaniasis, Diffuse Cutaneous/blood , Leishmaniasis, Diffuse Cutaneous/transmission
14.
Arq. bras. med. vet. zootec ; 68(4): 927-930, jul.-ago. 2016. ilus
Article in English | LILACS, VETINDEX | ID: lil-792467

ABSTRACT

Cutaneous leishmaniasis has several species of Leishmania as agents, and a wide variety of wild and domestic animals as hosts and different species of phlebotomines as vectors. A case of cutaneous leishmaniasis in a dog coming from an agricultural settlement is described. This is the first report of parasitism in a dog by Le. (Viannia) braziliensis in Mato Grosso do Sul State. Attention is called to the importance of including this protozoonosis in the differential diagnosis of dermopathies in dogs as also the need to assess the importance of the domestic dog as a possible reservoir of Le. braziliensis.(AU)


As leishmanioses tegumentares são antropozoonoses metaxênicas de importância em saúde pública. Possuem como agentes etiológicos várias espécies de Leishmania, com ampla variedade de hospedeiros, como animais selvagens e domésticos, e diferentes espécies de flebotomíneos como vetores. Um caso de leishmaniose tegumentar em um cão procedente de um assentamento agrícola em Mato Grosso do Sul é descrito, sendo este o primeiro relato de parasitismo em cão doméstico nesse estado por Le. (Viannia) braziliensis. Alerta-se para a importância de se incluir essa protozoonose no diagnóstico diferencial de dermopatias em cães e para a necessidade de se avaliar o papel do cão doméstico como reservatório de Le. (Vi.) braziliensis.(AU)


Subject(s)
Humans , Animals , Male , Female , Adolescent , Dogs , Disease Reservoirs/veterinary , Disease Vectors , Leishmania braziliensis , Leishmaniasis, Cutaneous/veterinary , Leishmania mexicana , Skin Ulcer/veterinary
15.
Mem. Inst. Oswaldo Cruz ; 111(7): 460-468, tab, graf
Article in English | LILACS | ID: lil-787557

ABSTRACT

The 70 kDa heat shock protein (HSP70) is a molecular chaperone that assists the parasite Leishmania in returning to homeostasis after being subjected to different types of stress during its life cycle. In the present study, we evaluated the effects of HSP70 transfection of L. amazonensis promastigotes (pTEX-HSP70) in terms of morphology, resistance, infectivity and mitochondrial bioenergetics. The pTEX-HSP70 promastigotes showed no ultrastructural morphological changes compared to control parasites. Interestingly, the pTEX-HSP70 promastigotes are resistant to heat shock, H2O2-induced oxidative stress and hyperbaric environments. Regarding the bioenergetics parameters, the pTEX-HSP70 parasites had higher respiratory rates and released less H2O2 than the control parasites. Nevertheless, the infectivity capacity of the parasites did not change, as verified by the infection of murine peritoneal macrophages and human macrophages, as well as the infection of BALB/c mice. Together, these results indicate that the overexpression of HSP70 protects L. amazonensis from stress, but does not interfere with its infective capacity.


Subject(s)
Animals , Female , HSP70 Heat-Shock Proteins/physiology , Leishmania mexicana/physiology , Leishmaniasis, Cutaneous/parasitology , Protozoan Proteins/physiology , Stress, Physiological , HSP70 Heat-Shock Proteins/genetics , Leishmania mexicana/genetics , Leishmania mexicana/ultrastructure , Macrophages/parasitology , Mice , Mice, Inbred BALB C , Mitochondria/physiology , Oxidative Stress , Protozoan Proteins/genetics , Transfection/methods
16.
Braz. j. infect. dis ; 19(3): 302-307, May-Jun/2015. tab, graf
Article in English | LILACS | ID: lil-751876

ABSTRACT

Background: Several tests are performed to obtain better accuracy when diagnosing American tegumentary leishmaniasis (ATL). It is believed that antigens released via secretion, excretion and metabolism are more specific than are antigens released by the lysis of Leishmania parasites. Such antigens are known as exo-antigens (exo-Ag) and are formed from products released by cultured parasites in a way that is similar to that in which they cause infections in hosts. Objective: We attempted to validate a Leishmania mexicana ELISA exo-Ag for ATL diagnosis in Midwestern Brazil. Methods: A total of 281 patients were included in the study. We analysed pre-treatment blood from 98 ATL patients; out of those, 85.7% and 14.3% had cutaneous and mucosal forms, respectively. Results: The exo-Ag accuracy was 83.99% (95% CI = 79.24-87.81) with a sensitivity value of 90.82% (95% CI = 83.46-95.09) and an overall specificity value of 80.33% (95% CI = 73.97-85.44). The positive predictive value and negative predictive value were 71.20% (95% CI = 62.72-78.41) and 94.23% (95% CI = 89.40-96.94), respectively. Among healthy controls, exo-Ag had a specificity of 91.25% (95% CI = 83.02-95.70); additionally, the test had specificity rates of 66.67% (95% CI = 46.71-82.03) in Chagas disease patients, 60.61% (95% CI = 43.68-75.32) in patients with rheumatic diseases, 76.92% (95% CI = 49.74-91.82) in pemphigus foliaceus patients, 87.50% (95% CI = 52.91-97.76) in leprosy patients, 87.50% (95% CI = 63.98-96.50) in VRDL-positive patients, and 77.78 (95% CI = 45.26-93.68) in deep mycosis patients. Conclusion: Based on the indicators of validity, we conclude that the results obtained in this study enable the recommendation of the exo-Ag ELISA for ATL diagnosis once it presented a reasonable accuracy compared to classical methods. Cost evaluations are necessary to completely define the role of this technique in large scale. .


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Antigens, Protozoan/blood , Enzyme-Linked Immunosorbent Assay/methods , Leishmania braziliensis/immunology , Leishmania mexicana/immunology , Leishmaniasis, Cutaneous/diagnosis , Case-Control Studies , Leishmaniasis, Cutaneous/parasitology , Predictive Value of Tests , Sensitivity and Specificity
17.
Cad. saúde pública ; 31(4): 682-690, 04/2015. tab, graf
Article in Portuguese | LILACS | ID: lil-744858

ABSTRACT

O objetivo do presente estudo foi avaliar, mediante revisão sistemática da literatura, as evidências acerca da associação entre consumo materno de cafeína durante a gestação e transtorno de déficit de atenção e hiperatividade (TDAH) na infância. A busca na literatura ocorreu de forma sistemática, em múltiplas etapas, nas bases PubMed, LILACS, BIREME e PsycINFO, com limites para artigos publicados em português, inglês e espanhol, realizados em humanos. Foram encontradas 373 referências. Dessas, somente cinco foram mantidas, por atenderem ao objetivo deste estudo. Os cinco trabalhos foram realizados em países desenvolvidos; a maioria utilizou delineamento longitudinal e foi publicada nos últimos cinco anos. Apenas um estudo encontrou associação positiva. Estudos sobre o consumo de cafeína na gestação e TDAH são escassos, com resultados controversos e se deparam com várias dificuldades metodológicas, como falta de padronização na definição do desfecho.


This aim of this study was to conduct a systematic literature review on the association between maternal caffeine intake during pregnancy and attention deficit hyperactivity disorder (ADHD) in childhood. The systematic multiple-stage literature search in PubMed, LILACS, BIREME, and PsycINFO was limited to research in human subjects and published in Portuguese, English, and Spanish. A total of 373 references were retrieved. Of these, only five met the study's objectives and were kept in the review. Most of the studies employed a longitudinal design, were conducted in developed countries, and were published in the last five years. Only one study found a positive association. Studies on caffeine consumption during pregnancy and ADHD are scarce, with conflicting results and several methodological difficulties such as lack of standardized outcome measures.


El objetivo de este estudio fue evaluar, a través de una revisión sistemática de la literatura, evidencias sobre la asociación entre el consumo de cafeína durante el embarazo y el trastorno por déficit de atención e hiperactividad (TDAH) en la infancia. Se realizó una búsqueda sistemática en la literatura, por etapas múltiples, en PubMed, LILACS BIREME y PsycINFO, limitándose a artículos publicados en portugués, inglés y español, realizados en estudios sobre humanos. Fueron localizadas 373 referencias. De ellas, apenas se mantuvieron cinco, por cumplir el objetivo de este estudio. Los estudios se realizaron en países desarrollados; el diseño longitudinal fue el más utilizado y se trata de publicaciones de los últimos cinco años. Sólo un estudio encontró asociación positiva. Los estudios sobre el consumo de cafeína durante el embarazo y el TDAH son escasos, con resultados controvertidos, y enfrentan varias dificultades metodológicas, como la no estandarización de la evaluación del resultado.


Subject(s)
Animals , Female , Mice , Leishmania mexicana/growth & development , Leishmania mexicana/immunology , Leishmaniasis, Cutaneous/immunology , Leishmaniasis, Cutaneous/parasitology , Neutrophils/immunology , Antibodies, Protozoan/blood , Arginase/metabolism , Immunoglobulin G/blood , /metabolism , /metabolism , Kinetics , Macrophage Activation , Mice, Inbred BALB C , Macrophages/immunology , Macrophages/metabolism , Macrophages/parasitology , Neutrophil Infiltration , Parasite Load , T-Lymphocytes, Regulatory/immunology
18.
Salud pública Méx ; 57(1): 58-65, ene.-feb. 2015. ilus, tab
Article in English | LILACS | ID: lil-736462

ABSTRACT

Objective. To study cutaneous leishmaniasis (CL), in the Calakmul municipality of the Campeche State, during two years. Materials and methods. Individuals with skin lesions were evaluated. Aspirates taken from the lesions were cultured, PCR was performed to diagnose the Leishmania species. Results. The culture detected 42% of the samples. PCR diagnosed CL in 76% of the samples; of those 38% were from children and 62% from adults. 89% of the patients were infected with L. mexicana; 14.4% with Mexican strains of L. mexicana; 7% with L. braziliensis; 3.6% with L. mexicana and L. braziliensis. The most affected villages with CL were Dos Lagunas Sur with 12.3%, La Mancolona with 6.5% and La Guadalupe with 2.2% of prevalence, respectively. After the treatment with Glucantime, 96% of the patients were healed. Conclusion. CL is an important public health concern in Calakmul, and the parasite causing it belongs to Leishmania mexicana and Leishmania braziliensis complexes.


Objetivo. Estudiar la leishmaniasis cutánea en Calakmul, Campeche, México, durante dos años. Material y métodos. Se estudiaron individuos con lesiones cutáneas, se tomaron aspirados y se inocularon medios de cultivo; se realizó la técnica de PCR para identificar la especie de Leishmania. Resultados. Los cultivos detectaron 42% de las muestras. Con la PCR se amplificaron 76% de las muestras, 38% fueron tomadas de niños y 62% de adultos. En 89% de las muestras positivas se identificó Leishmania mexicana, en 14.4% cepas mexicanas de L. mexicana, en 7% L. braziliensis y en 3.6% L. mexicana y L. braziliensis. En Dos Lagunas Sur se encontró una prevalencia de 12.3%, en La Mancolona 6.5% y en La Virgen 2.2%. Del total de los pacientes, 96% se curó con Glucantime. Conclusion. La leishmaniasis cutánea es un problema de salud pública en Calakmul y las especies causantes pertenecen a los complejos Leishmania mexicana y Leishmania braziliensis.


Subject(s)
Humans , Animals , Male , Female , Child , Adult , Leishmaniasis, Cutaneous/epidemiology , Organometallic Compounds/therapeutic use , Rodentia/parasitology , Leishmania braziliensis/isolation & purification , Remission Induction , Leishmania mexicana/isolation & purification , Disease Reservoirs , Prevalence , DNA, Protozoan/analysis , Leishmaniasis, Cutaneous/parasitology , Geography, Medical , Meglumine Antimoniate , Meglumine/therapeutic use , Mexico/epidemiology , Antiprotozoal Agents/therapeutic use
19.
Caracas; s.n; 2015. 57 p. tab, graf, ilus.
Thesis in Spanish | MTYCI, LILACS, MTYCI | ID: biblio-877971

ABSTRACT

La leishmaniasis comprende un grupo de enfermedades infecciosas causadas por parásitos protozoarios pertenecientes al género Leishmania, siendo un problema de salud pública alrededor del mundo. Esta enfermedad prevalece en 98 países tropicales con un estimado de 2 millones de casos nuevos por año. El control de la enfermedad es deficiente, ya que los tratamientos disponibles no son satisfactorios debido a la alta toxicidad, la generación de resistencia por los parásitos y los altos costos del tratamiento. Por lo tanto, se busca desarrollar nuevas alternativas terapéuticas para tratar la enfermedad. Los productos naturales constituyen una fuente ilimitada para la obtención de productos químicos que sirven de base para el desarrollo de nuevas drogas. Diversos extractos de plantas han mostrado actividad antiparasitaria, entre los cuales se encuentran los extractos de Carica papaya. Esta planta perteneciente a la familia Caricaceae, tiene una amplia gama de propiedades medicinales. El objetivo de este trabajo fue estudiar el efecto de extractos metanólicos de semillas de Carica papaya sobre promastigotes de Leishmania mexicana. Las semillas se secaron, se molieron y el polvo obtenido se maceró en metanol. El extracto se filtró, se concentró en un rotoevaporador y se resuspendió en dimetilsulfóxido (DMSO). Diversos compuestos fitoquímicos se lograron identificar en el extracto metanólico, tales como alcaloides, compuestos fenólicos, flavonoides, glicósidos cianogénicos, taninos y triterpenos. Los ensayos de citotoxicidad mediante el método de reducción de la sal de tetrazolio (MTT) revelaron un efecto citotóxico de los extractos contra los promastigotes (IC50= 0,18± 0,02 mg/ml) y un efecto inhibitorio del crecimiento de cultivos de promastigotes (IC50= 0,20± 0,05 mg/ml). Los extractos mostraron una menor actividad citotóxica sobre macrófagos murinos J774 con IC50 de 6,75 mg/ml, calculándose un Índice de Selectividad de 37. Los estudios por microscopía de contraste de fase, revelaron alteraciones en la morfología celular, la movilidad flagelar y la citocinesis de los promastigotes tratados con los extractos. Los resultados demuestran que los extractos metanólicos de semilla inhiben el crecimiento y causan alteraciones estructurales en promastigotes de L. mexicana, proporcionando nuevas perspectivas en el desarrollo de drogas con actividad antileishmanial obtenidas de productos naturales. Palabras clave: Leishmania mexicana, Carica Papaya, extracto metanólico, citotoxicidad.


Subject(s)
Humans , Alkaloids , Carica , Leishmania mexicana/drug effects , Cytotoxins , Plant Extracts
20.
Recife; s.n; 2015. 74 p. ilus, graf, tab.
Thesis in Portuguese | LILACS | ID: lil-773006

ABSTRACT

Os tripanossomatídeos são organismos caracterizados pelo controle póstranscricional da expressão gênica, principalmente em nível de tradução. Na tradução em eucariotos, tem grande destaque o complexo eIF4F, sendo um de seus principais componentes o fator de iniciação da tradução eIF4E. Já foram descritos em tripanossomatídeos seis homólogos para o eIF4E, nomeados EIF4E1 a 6. Em um estudo com Leishmania amazonensis, focado no EIF4E3, percebeu-se que seu perfil de expressão se alterava rapidamente numa curva de crescimento, com este apresentando ao menos duas bandas. As mudanças observadas sugeriam modificações pós-traducionais do tipo fosforilação, algo posteriormente confirmado. Analisando-se a sequência do EIF4E3 de Leishmania, foi possível identificar a presença de possíveis sítios de fosforilação e de ligação a parceiros funcionais como homólogos do eIF4G, outro componente do complexo eIF4F, e da proteína de ligação á cauda poli-A (PABP). No presente estudo foi analisado o perfil de expressão e a capacidade de ligação a parceiros funcionais do EIF4E3 de Leishmania superexpresso em células transfectadas e no qual foram introduzidas mutações em motivos específicos. Os resultados mostraram um perfil de expressão de ao menos três bandas para o EIF4E3 de L. amazonensis e duas para L. infantum, com o sítio S75, presente apenas na primeira, sendo o responsável por esta diferença...


Subject(s)
Humans , Animals , Gene Expression , Leishmania infantum/genetics , Leishmania infantum/metabolism , Leishmania mexicana/genetics , Leishmania mexicana/metabolism , Poly(A)-Binding Proteins , Protein Binding , Protein Biosynthesis , Protozoan Proteins , Sequence Homology, Nucleic Acid
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