Дисертації з теми "Leishmaniasis-Disease"
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Yakovich, Adam J. "Old targets and new beginnings a multifaceted approach to combating Leishmaniasis, a neglected tropical disease /." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1193247442.
Повний текст джерелаMARITATI, MARTINA. "LEISHMANIASIS: A RE-EMERGING NEGLECTED DISEASE. BIOMOLECULAR AND METABOLOMIC STUDIES AIMED AT IMPLANTING ITS CONTROL IN EMILIA-ROMAGNA." Doctoral thesis, Università degli studi di Ferrara, 2021. http://hdl.handle.net/11392/2487987.
Повний текст джерелаBackground. Leishmaniases (VL) represents a major health problem. The first part of the thesis evaluates by molecular techniques and cytokine analysis the prevalence of asymptomatic Leishmania infections in autoimmune rheumatic patients treated with biological drugs and living in Leishmania endemic foci in Italy. In the second part, the effect of the niacin analogue, 6-AN on Leishmania parasite growth and metabolism using the metabolomics technology was investigated. The pentose phosphate pathway (PPP), has been reported as a target of 6-AN, thus PPP might represent a good target. Methods. VL qualitative and real-time PCR were performed on DNA extracted from PBMCs from 50 autoimmune rheumatic patients treated with immunosuppressive biologic drugs for at least 5 years. Plasma cytokine concentrations were also measured in plasma from Leishmania DNA-positive and -negative rheumatic patients as well as from the healthy control group. In the 6-AN study, L. mexicana M379 and L. infantum PCM5 promastigotes were treated with 7.8 mM 6-AN and 2.17% DMSO for 24 hours. After vitality, infectivity of 6-AN-treated promastigotes to mouse macrophages, and 6-AN interactions with oxidizing compounds were also studied. Small metabolites were extracted and analysed by pHILIC-LC-MS in polarity switching mode and data were analysed with IDEOMv19 and MetaboAnalyst 3.0. Results.Eighteen out the 50 (36%) autoimmune rheumatic patients were positive for Leishmania DNA by conventional and/or quantitative PCR with a detection of high parasite burdens (1 to 136 parasite/ml in 4 patients, 1.000 to 40.000 in 11 patients and over 1.000.000 in 3 patients). Patients that were taking a steroid in association with the biological drug showed a higher positivity for circulating L. infantum kDNA than those given the biological drug only (p<0.05). Pro-inflammatory IL-1, IL-6, IL-12(p70), IL-7, IL-15, IFN-γ and TNF-α; anti-inflammatory IL-4, IL-13; and regulatory IL-10 cytokines were markedly elevated in all autoimmune rheumatic patients with additional increases in inflammatory mediators in autoimmune rheumatic patients positive for Leishmania DNA. In both L. mexicana and L. infantum, 6-AN caused significant depletion of phosphoribosylpyrophosphate (PRPP) and nicotinate (Na) and as a result purine and pyrimidine nucleotides were reduced and their nucleobases accumulated. Glutathione, ribose-5-phosphate, 6-phosphogluconate levels and downstream PPP intermediates were similar to controls. For L. infantum, it was possible to analyse NAD+ and NADPH, which were found decreased together with the PPP intermediate D-sedoheptulose 7-phosphate. Moreover, 6-AN treatment caused a marked elongation in parasite body. 6-AN in combination with the oxidizing compounds has additive effects against Leishmania and did not affect the infectivity of the treated promastigotes to mouse macrophages. Conclusions.VL molecular screening and cytokine analysis should be taken into account before treating autoimmune rheumatic patients with biologic drugs, especially in rural areas. In mammals 6-AN is converted to abnormal 6-ANAD/P by NAD+ glycohydrolase, however, in Leishmania its toxicity is only seen in millimolar range, in which 6-AN is responsible for the depletion of cellular phosphoribosyl pyrophosphate (PRPP) content probably in the Preiss-Handler NAD+ salvage pathway, resulting in depletion of nucleotides required for nucleic acid biosynthesis. The marked elongation in the 6-AN-treated parasite bodies confirms nucleotide starvation. Leishmania NAD+ glycohydrolase might decompose NAD+ but might not catalyze exchange reactions, as found in other microrganisms, however, combined 13C-glucose labeling and flux analysis might be useful to ascertain the fate and action mechanism of 6-AN in Leishmania. In addition, PRPP synthetase should also be a good target for new potential drugs against leishmaniasis pointing to the growth-inhibitory effect of PRPP depletion.
Boraschi, Cláudia Souza e. Silva [UNESP]. "Inquérito sobre o conhecimento da população da cidade de Três Lagoas – MS sobre leishmaniose visceral." Universidade Estadual Paulista (UNESP), 2007. http://hdl.handle.net/11449/94685.
Повний текст джерелаCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
A leishmaniose visceral (LV) é um importante problema de saúde pública e as medidas de prevenção preconizadas nem sempre são conhecidas pela população. Esta pesquisa avaliou, por meio da aplicação de um questionário, o conhecimento que a população de Três Lagoas, MS tem sobre esta zoonose. Dos 384 entrevistados, 100% afirmaram que já tinham conhecimento prévio da LV, 64,5% sabiam que é transmitida através do inseto vetor e 65,4% sabiam que a prevenção se dá evitando o criadouro deste. Observaram-se 93,5% de respostas para manutenção do quintal limpo como medida preventiva conhecida. Pelo menos um método de prevenção era utilizado no animal por 50,5% dos entrevistados e observou-se associação estatisticamente significante entre o grupo de proprietários cujos cães nunca apresentaram leishmaniose visceral canina e o grupo que fazia uso de alguma prevenção no animal (p=0,0006).
Visceral Leishmaniasis (VL) is an important public health problem and the measures to prevent it are not always known by the population. This research evaluated the knowledge that the population of Três Lagoas, MS, Brazil has about this zoonosis. One hundred percent of the interviewed (384) had previous knowledge of the disease, 64.5% knew that a vector transmits it and 65.4% knew that the prevention is achieved by preventing vector’s breeding sites. Maintenance of the backyard clean was informed by 93,5% as a known preventive measure. At least one preventive method was used in the animal by 51% of the interviewed ones and statically significant association between the group of owners whose dogs had never presented canine visceral leishmaniasis and owners that used some preventive method in the animal (p=0.0006) was observed.
Sánchez, Fabio. "Genetic factors influencing susceptibility to intracellular infections /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-225-6.
Повний текст джерелаCollar, Catharine Jane. "Rational Drug Design for Neglected Diseases: Implementation of Computational Methods to Construct Predictive Devices and Examine Mechanisms." Digital Archive @ GSU, 2010. http://digitalarchive.gsu.edu/chemistry_diss/48.
Повний текст джерелаBhattacharyya, T. "Parasite diversity and innovative serology : development of Trypanosoma cruzi lineage-specific diagnosis of Chagas disease and of prognostic assays for visceral leishmaniasis." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2015. http://researchonline.lshtm.ac.uk/2173663/.
Повний текст джерелаFurini, Júnior. "Estratégias terapêuticas usando o ácido ursólico sobre infecções determinadas por tripanosomatideos." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/60/60135/tde-12122016-154937/.
Повний текст джерелаChagas disease and Leishmaniasis are diseases caused by protozoa of the family Trypanosomatidae (Trypanosoma cruzi and Leishmania sp., Respectively) and both are in the group of diseases considered neglected tropical (NTDs). All together, they affect about 30 million people in 98 countries worldwide. Although so very epidemiologically important, these diseases still lack a safe and robust chemotherapeutic treatment seeing that the available drugs present besides low therapeutic efficacy, low compliance rates, since they are extremely toxic and cause serious side effects ending up, therefore, being resistance generators. In recent decades, there have been intense efforts of research groups to develop alternatives for treating these diseases, especially exploring natural products and by applying pharmaceutical technology, generating more clinically viable formulations due to providing favorable physicochemical properties to the cell absorption and permeability, thus resulting in increased bioavailability and enhancement of biological effect. In our present study, we aimed to propose new treatment strategies for these diseases by using as a candidate, the ursolic acid (UA), a naturally occurring triterpenoid. Isolated UA and associated with established drugs have been tested, as well as a solid dispersion containing 10% of the active ingredient (SDUA). In the in vitro tests against several extracellular and intracellular evolving forms of Trypanosoma cruzi and Leishmania braziliensis, we have obtained very good results, such as 99.8 of lysis at 128 ?M on trypomastigotes, with IC50 of 14.1 ?M for the UA. In the in vivo experiments about experimental Chagas disease, a decrease of parasitaemi of 60.2% and 61.6% has been observed in animals treated with doses of 20 mg / kg of UA and SDUA respectively. Although not having caused a decrease in the parasite load in the tissues analyzed (heart and liver) compared to the negative control, the PFS of animals treated with UA and SDUA was similar to that of the animals treated with the same dose of benznidazole. About the experimental skin mucus leishmaniasis, we have observed a decrease of the average diameter of lesions in animals treated with 20 mg / kg of our evaluated compounds. These results demonstrate that the ursolic acid is a potent candidate for chemotherapy for the treatment of trypanosomiasis. Furthermore, the association of existing drugs, and the use of pharmaceutical technology can be good strategies to treat these diseases
Boraschi, Cláudia Souza e. Silva. "Inquérito sobre o conhecimento da população da cidade de Três Lagoas - MS sobre leishmaniose visceral /." Araçatuba : [s.n.], 2007. http://hdl.handle.net/11449/94685.
Повний текст джерелаBanca: Mary Marcondes
Banca: Sonia Regina Pinheiro
Resumo: A leishmaniose visceral (LV) é um importante problema de saúde pública e as medidas de prevenção preconizadas nem sempre são conhecidas pela população. Esta pesquisa avaliou, por meio da aplicação de um questionário, o conhecimento que a população de Três Lagoas, MS tem sobre esta zoonose. Dos 384 entrevistados, 100% afirmaram que já tinham conhecimento prévio da LV, 64,5% sabiam que é transmitida através do inseto vetor e 65,4% sabiam que a prevenção se dá evitando o criadouro deste. Observaram-se 93,5% de respostas para manutenção do quintal limpo como medida preventiva conhecida. Pelo menos um método de prevenção era utilizado no animal por 50,5% dos entrevistados e observou-se associação estatisticamente significante entre o grupo de proprietários cujos cães nunca apresentaram leishmaniose visceral canina e o grupo que fazia uso de alguma prevenção no animal (p=0,0006).
Abstract: Visceral Leishmaniasis (VL) is an important public health problem and the measures to prevent it are not always known by the population. This research evaluated the knowledge that the population of Três Lagoas, MS, Brazil has about this zoonosis. One hundred percent of the interviewed (384) had previous knowledge of the disease, 64.5% knew that a vector transmits it and 65.4% knew that the prevention is achieved by preventing vector's breeding sites. Maintenance of the backyard clean was informed by 93,5% as a known preventive measure. At least one preventive method was used in the animal by 51% of the interviewed ones and statically significant association between the group of owners whose dogs had never presented canine visceral leishmaniasis and owners that used some preventive method in the animal (p=0.0006) was observed.
Mestre
Zuque, Maria Angelina da Silva. "Participação de gambás e cães domiciliados como reservatórios de Leishmania infantum e Trypanosoma cruzi georreferenciados nos municípios da Regional de Saúde de Três Lagoas - MS." Botucatu, 2016. http://hdl.handle.net/11449/136267.
Повний текст джерелаResumo: A Leishmaniose Visceral e a Doença de Chagas são importantes zoonoses negligenciadas do ponto de vista de saúde pública. Animais domésticos, como o cão, e animais silvestres, como os gambás, fazem parte do ciclo destas zoonoses como fontes de infecção para os vetores. O estudo foi realizado em cinco municípios da Regional de Saúde de Três Lagoas, Mato Grosso do Sul, em 2013 e 2014, com objetivo de identificar a ocorrência da infecção natural por Leishmania spp e Trypanosoma cruzi em gambás (Didelphis albiventris) e cães domiciliados, descrever aspectos epidemiológicos dessas doenças na população canina e humana, seus vetores, e a distribuição espacial da Leishmaniose Visceral Canina usando técnicas do georrefenciamento. Amostras de sangue dos cães foram submetidas a análises sorológicas e moleculares, e a dos gambás somente as análises moleculares. Em relação à pesquisa de anticorpos contra a Leishmania spp., as provas sorológicas de 683 amostras dos cães, revelaram reagentes 320 amostras ao Dual Path Platform, 300 amostras ao Enzyme Linked Immunosorbent Assay e 116 a Reação de Imunofluorescência Indireta. Para Trypanosoma cruzi, pela Reação de Imunofluorescência Indireta, quatro amostras do município de Três Lagoas foram reagentes. Das 683 amostras de sangue total, dos cães submetidas à Reação em Cadeia pela Polimerase, todas foram negativas para Trypanosoma cruzi e obteve-se êxito na amplificação de Leishmania spp em 17 amostras. As 39 amostras de sangue total dos gambás fo... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Visceral Leishmaniasis (VL ) and Chagas disease (CD ) are important neglected zoonoses in accordance with public health. Domestic animals such as dogs and wildlife such as possums , are part of these zoonoses cycles as reservoirs and sources of infection for vectors. The study was conducted in five Regional Health of the municipalities of Três Lagoas , Mato Grosso do Sul in 2013 and 2014 , in order to verify the occurrence of natural infection with Leishmania infantum and Trypanosoma cruzi in opossums (Didelphis albiventris) and the pet dogs, and describe the characteristics of diseases in human and canine population , vectors , and the spatial distribution of canine Visceral Leishmaniasis using techniques georrefenciamento. In dog´s blood there were performed serological analysis and molecular tests ande the samples of the opossums were performed molecular tests. Regarding the research for Leishmania antibodies the techniques serological to 683 dog samples, showed reagent 320 samples to Dual Path Platform, 300 samples to Enzyme Linked Immunosorbent Assay and 116 to Immunofluorescence Antibody Test. For Trypanosoma cruzi, the test Immunofluorescence Antibody Test (IFAT) four samples of Três Lagoas municipality were reactive. Of the samples from dogs 683 submitted to the Polymerase Chain Reaction were all negative by Trypanosoma cruzi gave successful amplification Leishmania spp in 17 of them. The 39 samples of the opossums were all negative by PCR to Leishmania spp. and Trypa... (Complete abstract click electronic access below)
Doutor
Barbosa, Sofia Diniz de Nazaré. "A leishmaniose canina e os condicionalismos determinados pelas respectivas alterações renais." Bachelor's thesis, Universidade Técnica de Lisboa. Faculdade de Medicina Veterinária, 2011. http://hdl.handle.net/10400.5/3548.
Повний текст джерелаA Leishmaniose é uma doença zoonótica causada pelo protozoário da espécie Leishmania infantum, que existe predominantemente na Bacia do Mediterrâneo. O ciclo de vida deste parasita requer a existência de um vector, um insecto do género Phlebotomus, que é responsável pela transmissão das formas infectantes, os promastigotas metacíclicos, aos hospedeiros vertebrados, nomeadamente os canídeos. Em Portugal, apenas as espécies P. ariasi e P. perniciosus são vectores comprovados de L. infantum. As características clínicas da Leishmaniose canina variam amplamente como consequência dos numerosos mecanismos patogénicos do protozoário, da diversidade de respostas imunológicas desenvolvidas nos hospedeiros e dos diferentes órgãos afectados. A doença renal pode ser a única manifestação clínica nos animais infectados, podendo progredir de proteinúria assintomática até síndrome nefrótico ou Insuficiência Renal Crónica, que é responsável pela degradação do estado geral e a principal causa de morte nos cães com Leishmaniose. A aplicação do tratamento adequado requer, previamente, um diagnóstico precoce da doença e a avaliação do estado sanitário e imunitário do animal, através do exame clínico e de exames complementares, que devem ser repetidos a cada 6 meses. A presença de Insuficiência Renal Crónica impõe algumas limitações no tratamento da Leishmaniose canina, sendo fundamental seleccionar cautelosamente os fármacos e respectivas doses a administrar a cada paciente. Neste estudo retrospectivo foram observados 19 canídeos com Leishmaniose, sendo a sua sintomatologia muito variável, da qual se destaca a linfadenopatia, o emagrecimento e as lesões dermatológicas. As alterações laboratoriais mais frequentes foram a anemia não-regenerativa, a trombocitopénia, a hiperproteinémia com hiperglobulinémia e a proteinúria. O diagnóstico etiológico foi realizado com base nas técnicas de imunocromatografia rápida e de imunofluorescência indirecta. Foi também diagnosticada Insuficiência Renal Crónica em 4 canídeos da amostra. Diferentes fármacos foram utilizados no tratamento etiológico e sintomático, porém foi mais frequente a administração de alopurinol em monoterapia ou em associação com o antimoniato de glucamina.
ABSTRACT - CANINE LEISHMANIASIS AND CONSTRAINTS DETERMINED BY THEIR RENAL CHANGES - Leishmaniasis is a zoonotic disease caused by the protozoan Leishmania infantum, which is the most common species of Leishmania in the Mediterranean basin. The life cycle of this parasite requires the existence of a vector, the insect of the genus Phlebotomus, which is responsible for the transmission of infectious form, the metacyclic promastigotes, to the vertebrate host, namely the dog. In Portugal, only the species P. ariasi and P. perniciosus are proven vectors of L. infantum. The clinical features of canine Leishmaniasis are highly variable as a consequence of the numerous pathogenic mechanisms, the diversity of immune responses of individual hosts and the different organs affected. Renal disease may be the only clinical manifestation in infected dogs and may progress from asymptomatic proteinuria to nephrotic syndrome or to Chronic Kidney Disease, which is responsible for the deterioration of general condition and leading cause of death in dogs with Leishmaniasis. The application of suitable treatment requires, previously, an early diagnosis and assessment of dog’s health and immunity status, by clinical examination and several routine diagnostic tests, which must be repeated every six months. The presence of Chronic Kidney Disease imposes some limitations in the treatment of canine Leishmaniasis and is necessary to select carefully the drugs and doses to be administered in each patient. In this retrospective study, 19 dogs with Leishmaniasis were observed and many clinical signs were found, mainly lymphadenopathy, weight loss and dermatologic lesions. The most frequent laboratory abnormalities were non-regenerative anemia, thrombocytopenia, hyperproteinemia with hyperglobulinemia and proteinuria. The definitive diagnosis was made by a rapid immunomigration test and indirect fluorescent antibody technique. Chronic Kidney Disease was also diagnosed in 4 dogs of sample. Different drugs were used in the etiological and symptomatic treatment, but the administration of alopurinol alone or in combination with glucamine antimoniate were the most frequent.
Santos, Anderson Pacheco dos. "Sorologia de leishmaniose tegumentar americana em areas de avaliação de infecção chagasica no estado de São Paulo, Brasil." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/315103.
Повний текст джерелаDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: As zonas endêmicas de leishmanioses e doença de Chagas, duas grandes endemias causadas por cinetoplastídeos, sobrepõe-se na América do Sul, especialmente na região Sudeste do Brasil, o que pode gerar casos de co-infecção entre Leishmania spp. e Trypanosoma cruzi. Ocorrem reações cruzadas, mesmo com baixos títulos, em inquéritos sorológicos de pacientes infectados com os parasitas, o que leva a falsas estimativas de prevalência de ambas as infecções. Este trabalho tem o objetivo de observar o efeito de um diluente de amostra proposto para reduzir a ocorrência de reações cruzadas em testes sorológicos para doenças causadas por cinetoplastídeos e outros parasitas. Foram selecionadas 585 amostras de sangue provenientes de quatro regiões do Estado de São Paulo, entre litoral e planalto, colhidas no período compreendido entre 1996 a 2003, durante atividades do Programa de Controle da Doença de Chagas. As análises das amostras foram feitas através das Reações de Imunofluorescência (RIFI) e do ensaio imunoenzimático (ELISA). Com as amostras reagentes (onze no total), para doença de Chagas e leishmaniose em ambas as técnicas, foi realizado o teste ELISA alta avidez, que utiliza um diluente com caotrópico, que demonstrou redução nos títulos da reação positiva falsa, restando apenas uma amostra sem redução significativa do seu título, que sugeriu ser um caso de co-infecção de doença de Chagas e leishmaniose, epidemiologicamente factível dada a existência de ambas as infecções na área estudada. O uso deste diluente em estudos clínicos e epidemiológicos pode aprimorar o diagnóstico para a identificação de soropositivos em regiões de sobreposição de endemias causadas por cinetoplastídeos
Abstract: Leishmaniases and Chagas disease are endemic in extensive areas of the American Continent. These parasitic diseases can occur together in South America, particularly in southwestern regions of Brazil, which poses a serious epidemiological problem due to the observed serological cross-reactivity between Leishmania spp. and Trypanosoma cruzi, even at low titers. As false prevalence estimates of these agents are critically misleading, we designed an experiment aiming at analyzing the effect of a diluent intended to reduce the chances of false positive tests resulting from serological cross-reactivity between these kinetoplastids and other parasites. As a part of the activities of the Program for the Control of Chagas disease, we selected 585 blood samples collected, during the period from 1996 to 2003, from residents in four regions situated between the seacoast and the plateau of the State of São Paulo. The serological tests used (IFAT and ELISA) produced a total of eleven positive reactions. Lower false positive titers resulted from the use of high avidity ELISA plus a chaotropic diluent. The only serological result in which titers corresponding to both infections were not significantly reduced was suggestive of mixed infection, on the basis of the fact that it was connected to a patient evidently exposed to both agents. This experiment suggests that the use of a chaotropic diluent can be a useful tool to reduce the proportion of such false parasitic mixed infection results as those investigated by us
Mestrado
Mestre em Parasitologia
Frade, Amanda Farage. "Identificação de polimorfismos genéticos com impacto no desenvolvimento e progressão da leishmaniose visceral em indivíduos de áreas endêmicas do Maranhão e Piauí." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-27082010-165613/.
Повний текст джерелаVisceral leishmaniasis is a serious protozoan infectious disease caused by an obligate intracellular parasite. Some factors can affect the severity of the clinical manifestations; one of which is genetic susceptibility. This study investigated polymorphisms in the TGFB1, IL8 and IL6 genes, which are cytokines related with the onset and severity of the disease, to look for genetic susceptibility factors. Polymorphisms at TGFB1 -509C/T and +869T/C, and IL8 - 251A/T and IL6 -174G/C were analyzed by a PCR-RFLP technique, in 198 patients with Visceral Leishmaniasis (VL), 98 individuals with asymptomatic infection (positive delayed-type hypersensitivity, DTH+) and 100 individuals with no evidence of infection (DTH-). The T allele of the TGFB1 polymorphism in position -509C/T conferred a two risk fold to develop LV or to be DTH+ (p=0.007; OR=1.9 [1.19 - 3.02]) when compared with DTH- individuals. We suggest the TGFB1 -509C/T polymorphism is associated with susceptibility to LV and may contribute to development of the clinical disease.
Kinkead, James Robert H. "Study of the molecular regulation of trypanosomatid phosphofructokinases as drug targets." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31144.
Повний текст джерелаDavis, Richard Elliot. "Neutrophil responses to infection with leishmania parasites: MHC class II-expression and parasite life-stage interactions." Diss., University of Iowa, 2016. https://ir.uiowa.edu/etd/2200.
Повний текст джерелаBispo, Ana Jovina Barreto. "Avaliação de alterações pulmonares na leishmaniose visceral humana." Universidade Federal de Sergipe, 2015. https://ri.ufs.br/handle/riufs/3882.
Повний текст джерелаA leishmaniose visceral (LV) é uma zoonose grave de ampla incidência mundial. Caracteriza-se pelo envolvimento sistêmico e alto potencial de letalidade. O pulmão, assim como qualquer outro órgão, pode estar envolvido na sua patogênese. A tosse é um sintoma descrito com frequência nas formas sintomáticas da LV, porém, pouco estudada. As principais alterações pulmonares descritas são histológicas e imunológicas, caracterizadas por uma resposta inflamatória predominantemente intersticial e padrão imunológico do tipo Th2. Existe, no entanto, uma lacuna envolvendo as características funcionais pulmonares. Este estudo, de delineamento transversal, objetivou descrever a sintomatologia e a radiologia pulmonar, e, também, determinar a frequência de alterações funcionais em pacientes portadores de LV, através da realização de avaliação clínica, exame físico, radiografia de tórax e espirometria em pacientes com diagnóstico de LV durante sua internação. Participaram do estudo 33 pacientes internados no Hospital Universitário da Universidade Federal de Sergipe, no período de julho de 2013 a julho de 2014. A amostra ficou assim caracterizada: metade dos pacientes possuía idade até 14 anos; houve predominância do sexo masculino (72,7%); a maior parte dos pacientes foi procedente da capital do Estado (42,2%); 87,9% dos indivíduos tiveram diagnóstico nutricional de eutrofia; a mediana de tempo decorrido entre o início dos sintomas e o internamento foi de 30 dias. Sintomas respiratórios estiveram presentes em 14 pacientes (42,4%). A radiografia de tórax foi considerada anormal em quatro (12%). A espirometria mostrou 56,3% de frequência de alterações funcionais e média dos valores VEF1, CVF, VEF1/CVF, FEF25-75% abaixo dos valores previstos. O distúrbio ventilatório predominante foi o restritivo (37,5%), seguido do distúrbio misto (12,5%) e do distúrbio obstrutivo (6,3%). A frequência de sintomas respiratórios evidencia envolvimento pulmonar na LV. A média dos valores medidos de CVF e do VEF1 significativamente menor em comparação à média dos valores previstos e o elevado percentual de alterações espirométricas demonstram a presença de distúrbios funcionais no sistema respiratório. A predominância do distúrbio ventilatório restritivo pode estar relacionada com a principal alteração pulmonar descrita na LV, a doença pulmonar intersticial.
Santos, Priscilla Vargas Walsh Gonçalves dos. "Relação imunogenética dos pênfigos com a leishmaniose tegumentar." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/17/17138/tde-20072016-144443/.
Повний текст джерелаPemphigus is an autoimmune bullous dermatosis, endemic in some areas, such as in the northeastern of São Paulo state, characterized by the production of autoantibodies against desmoglein (Dsg) - keratinocytes adhesion proteins. Pemphigus vulgaris (PV) affects mucous membranes and skin, by the production of anti-Dsg 3 and 1, respectively. Pemphigus foliaceus (PF) affects only the skin, by the production of anti-Dsg 1. This region is also endemic for American Cutaneous Leishmaniasis (ACL), whose main etiological factor is Leishmania (V.) braziliensis. Objectives: To relate immunogenetic factors of pemphigus with those of ACL, investigating, in patients with pemphigus, ACL and controls: the humoral response to Dsg 1 and 3; the humoral and cellular responses to Leishmania antigens; and the association of class II -DR and -DQ HLA alleles in ACL group with those of susceptibility and resistance described in pemphigus. Methods: The humoral response was investigated by (i) ELISA for determination of anti-Dsg1 and anti-Dsg3 antibodies and anti-antibodies from T. cruzi and L. braziliensis; (ii) immunoblotting (IB) with protein extract of the epidermis and protein extract of L. braziliensis; (iii) indirect immunofluorescence (IIF) with human skin substrate and serum of ACL patients. The cellular response was carried out by intradermal test Montenegro (ITM). The typing of HLA-DQ and -DR alleles was performed by PCR-SSOP. Results: The humoral response to Dsg confirmed expected in groups of PV and PF (anti-Dsg1: 84.6% in the PF group and 54.8% in the PV group, and anti-Dsg3: 83.9% in PV), with no significant difference between the ACL and control groups [anti-Dsg1: 16% in relatives of PF (RPF), 5.2% in the ACL, 4.2% in relatives of PV (RPV) and 2.7% of controls neighbors; anti-Dsg3: 12% in RPF, 6.4% in the PF group and 5.2% in ACL)]. There has been recognition of peptides 130kDa, 145 kDa, 150kDa, 160kDa, 230 kDa, 250 kDa, 290 kDa, 350 kDa, 410 kDa, 425 kDa and 460 kDa of human epidermis by serum of ACL patients. The IFI was positive in 1/6 ACL patients evaluated. The humoral response to L. braziliensis resulted higher in ACL group (73% to ACLc and 62% to ACLm) compared to the other groups, with no significant difference between pemphigus groups (1.3% in the PF group and 1.6% the group PV) and controls (10.8% in neighboring controls and 4% in FPF, in FPV and BS controls). Patients with pemphigus have serological titers to T. cruzi similar to controls. There was L. braziliensis recognition of peptides by the patients with pemphigus (45 kDa, 95 kDa, 100 kDa, 120 kDa, 125 kDa, 145 kDa, 150 kDa, 305 kDa, 330 kDa, 410 kDa and> 500 kDa). The ITM was negative in 06 patients with PF or PV evaluated. The DRB1*01:02 and DQA1*01 showed resistance association for LTA and susceptibility to PF; allele DRB1*04:02 resistance to ACL and susceptibility to PV; the DRB1*07: 01 and *11:01 susceptibility to ACL and resistance to PF; and DQA1*01:02 showed susceptibility association with both ACL and PF. Conclusions: Patients with ACL have humoral response to Dsg 1 and 3, and pemphigus patients to L. braziliensis and T. cruzi antigens similar to controls. The peptides recognized by patients with pemphigus to L. braziliensis extract require sequencing. The susceptibility or resistance associations of class II -DR and -DQ HLA alleles are opposed to ACL and pemphigus. The results confirm the non-participation of the parasite L. (V.) braziliensis in the pathogenesis of pemphigus, as well as support the clinical observation of the absence of both diseases association
Pinto, Erika Gracielle. "Isolamento, caracterização e atividade anti-leishmania chagasi e anti-trypanosoma cruzi de compostos bioativos de venenos de anfíbios brasileiros." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/99/99131/tde-31012014-154317/.
Повний текст джерелаAmong the tropical parasitic diseases, those caused by protozoa present a major challenge to public health, being represented by leishmaniasis and Chagas disease. Affect large populations marginal to the global economic process, and thus are not seen as potential markets. This project aimed the isolation of new natural compounds in animal venoms with anti-Leishmania activity and anti-T. cruzi. The present study fractionated by different chromatographic techniques, the poisons of the amphibians Siphonops annulatus, Corythomantis greeningi, Aparasphenodon brunoi and Phyllomedusa hypochondrialis, aiming the isolation of peptides and secondary metabolites through bioguided assays. By using mass spectrometry and sequencing by Edman degradation, it was possible to do the biochemical characterization of five active peptides from the poison of Phyllomedusa hypochondrialis, as bradykinin, dermaseptins 1 and 4 and phylloseptins 7 and 8. The peptides showed a 50% Effective Concentration (EC50) ranging from 0.7 to 20 ?g/mL in L. (L.) infantum chagasi and T. cruzi, with little or no cytotoxicity to mammalian cells at the tested concentrations. In addition, the chemical separation of the poison of the amphibian Siphonops annulatus provided a highly active fraction against promastigotes of L. (L.) infantum chagasi, with an EC50 of 0.065 ?g/mL, but highly toxicity to peritoneal macrophages and without selectivity against the intracellular forms of Leishmania. Ultrastructural studies of Leishmania showed severe mitochondrial damages and the formation of large cytoplasmic vacuoles, leading to parasite death within few hours. The present study demonstrated the potential of peptides and secondary metabolites of amphibian poisons, and if adequately studied, may contribute as prototypes of new drugs for neglected diseases.
Turra, Kely Medeiros. "Síntese de nitroderivados potencialmente antichagásicos e leishmanicidas para uso em sistemas ADEPT." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/9/9138/tde-08062017-101918/.
Повний текст джерелаNeglected diseases affect millions of people around the world for the most part in underdeveloped countries. Leishmaniasis and Chagas disease are example of important public health problems spread through Africa, Asia and Latin America. Unfortunately, currently available chemotherapy to treat these diseases remains ineffective, being the most frequently applied drugs toxic, expensive and of moderate potency. By considering this actual picture and envisioning new therapeutic alternatives, the aim of this work was to design and synthesize potential antichagasic and antileishmanial prodrugs of nitroderivatives to be used in Antybody-Directed Enzyme Prodrug Therapy (ADEPT), a drug design approach which results in targeted delivery of the active compounds, increasing their potencies in addition to lowering their toxicity. Theoretical studies to determine the catalytic mechanism of the carboxypeptidase G2 (CPG2) and to obtain information about the cleavage mechanism of proposed prodrugs were performed whereas different synthetic approaches were made to obtain the compounds. Docking and molecular studies of the CPG2 considering theoretical interactions with its known substrate, methotrexate, indicated that the proposed general mechanism for metalloproteases could be indeed applied to this enzyme. Information about the cleavage mechanism of prodrugs was also obtained. Initially prodrugs proposed were composed by nitroderivatives structures attached to glutamic acid, the chosen transporter agent, by a spacer group, the succinic acid. Theoretical studies, however, had showed that prodrugs constructed without a spacer agent could be better recognized by the enzyme. These results re-directed the synthetic approach to new prodrug structure without spacer. Despite all efforts spent, it was impossible to obtain the proposed prodrug structures. Experimental reactivity studies were then accomplished, since it was possible that the nitro group, from nitroderivatives structure, was able to reduce the nucleophilic power of particular functional groups chosen to accomplish the coupling between the active compound and the transporter. The results corroborate this hypothesis and the absence of nitro group facilitates the prodrug synthesis. This, however, constitute an important problem to be solved since the nitroderivative seams to exert their function mainly by nitro group reduction and production of free radical species in the surrounding of the parasites.
Tezuka, Daiane Yukie. "Triagem de compostos anti-chagásicos com o Trypanosoma cruzi e leishmanicidas com as espécies Leishmania amazonensis e Leishmania chagasi." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/75/75133/tde-25112015-101003/.
Повний текст джерелаInfections caused by trypanosomatides lead to thousands of deaths annually, besides the reduction of the quality of life and working capability, with high morbidity to the patients. The therapy efficacy is limited in most cases, being benznidazole the only approved drug in Brazil, which works only in the acute phase of the Chagas Disease with severe collateral effects. For leishmaniasis, the drugs cause renal and cardiac toxicity and trigger resistance. In this context, novel efficacious and secure substantes are necessary to improve the current therapeutic strategies, which was the goal of this project by means of cell-based assays. The first step was the standardization of the MTT colorimetric assay for the epimastigote form of the Y strain of Trypanosoma cruzi and promastigote form of Leishmania chagasi and Leishmania amazonensis. This was achieved by comparing the results with the standard counting using the Neubauer chamber. The use flow cytometry for the determination of cell viability and the perturbation of the cell cycle were also standardized using the reference drugs benznidazole (T. cruzi) and amphotericin B (Leishmania spp.). New compounds tested in this project were designed or selected based on different macromolecular targets (cysteine proteases, DHODH, GAPDH, kinases) by the Medicinal Chemistry Group (NEQUIMED). Among them, many kinase inhibitors promoted the most dramatic results for T. cruzi, reducing the cell viability of this parasite. One of them (Neq0474) was subjected for a follow-up dose-response assay, with EC50 = 53 µmol/L. L. chagasi was the most resistant parasite in this work, whereas L. amazonensis was sensitive to Neq0438. Some of these new compounds are of interest for more in-depth studies to these parasitic diseases.
Alessi, Claudia Alvares Calvo. "Leishmaniose cutânea americana no Pontal do Paranapanema - SP: avaliação clínica, histopatológica e uso da reação em cadeia da polimerase (PCR) para identificação e caracterização das espécies de Leishmania." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/5/5144/tde-17022009-115336/.
Повний текст джерелаLeishmaniasis are parasitic diseases caused by protozoans of the Leishmania genus and are important public health problems. American cutaneous leishmaniasis (ACL) is considered an autochthonous disease of the American continent and presents several clinical forms which depend on the causative species of the infection and other factors such as virulence and ability to evade the immune system. Six Leishmania species are recognized to cause human ACL cases in Brazil of which five belong to the Viannia and one to the Leishmania subspecies. They are: Leishmania (Viannia) braziliensis, Leishmania (Viannia) guyanensis, Leishmania (Viannia) lainsoni, Leishmania (Viannia) shawi, Leishmania (Viannia) naiffi and Leishmania (Leishmania) amazonensis. Cutaneous leishmaniasis transmission is maintained in the Pontal do Paranapanema region, with 20 notified cases in 2006. Leishmania (V.) braziliensis is the only species considered to be the disease agent in the region with identification of the involved vectors and possible wild reservoirs. The aim of this research is the studies of the epidemiological, clinical and histopathological aspects of cutaneous leishmaniasis in the Pontal do Paranapanema and the identification by molecular methods, PCR, of the etiologic agent and characterization of the Leishmania genus, subgenus and species present in the region. The disease was found in both genders, with predominance of males (67.9%), in all age ranges, but 70.5% were in the range of 20 to 49 years. The cutaneous was the mostly found clinical form with 92.3% of the cases. Search for the parasite in the lesion of 78 patients who underwent biopsies was positive in 40 samples (51.5%), in HE stained slides; when IH was used, 66.7% were positive. Agreement index between the HE and IH techniques were 58.97%. However, 10 negative cases using IH were positive with HE, and of 38 HE negative cases 22 were positive using IH. This shows that association of the two methods is needed. Using PCR, there was a positivity of 53.8%. Evaluating the results obtained in this study, we may observe that of the 40 HE positive cases 24 were also positive on PCR; but 16 of these were PCR negative. Contrariwise, of the 38 HE negative samples 18 were positive PCR. Using immunohistochemistry, of the total of 38 HE negative samples, 18 were positive with PCR; while of the 52 IH positive samples, 28 were positive and 24 negative on PCR. Agreement levels of PCR with HE were 56.41%, and of PCR with IH 51.28%. These results reinforce the idea of the need for association of the three methods for CL diagnosis. Histopathological lesion characteristics were: granulomatous reaction (GR) found in 71.85%, granulomatous reaction with giant cells (GRGC) in 12.8T, granulomatous reaction with necrosis (GRN) in 10.3% and granuloma with necrosis and giant cells (GRNGC) in 5.1% of the cases. Using SSU rDNAS 17/S18 primers it was possible to characterize through sequencing 27 (34.6%) samples as being of the Viannia subgenus and 06 samples of the L. (L.).amazonensis This study identified the first L. (L.) amazonensis case in the region
Abbehusen, Melissa Moura Costa. "Imunização de cães com produtos oriundos de Lutzomyia Longipalpis em duas diferentes abordagens: Canarypoxvirus sp. expressando o gene que codifica para a proteína salivar LJM17 e/ou LJL143, e a proteína do intestino médio luloper1 como vacina a proteína salivar LJM17 e/ou LJL143, e a proteína do intestino médio luloper1 como vacina bloqueadora de transmissão." reponame:Repositório Institucional da FIOCRUZ, 2015. https://www.arca.fiocruz.br/handle/icict/12697.
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Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
As interações entre flebótomo, parasita e hospedeiro desempenham um papel importante na transmissão da leishmaniose. As moléculas provenientes do vetor são relevantes para estas interações e incluem as proteínas da saliva e do intestino médio. Nos flebótomos, as Leishmanias passam por um ciclo de desenvolvimento complexo dentro do intestino médio sob a proteção da matriz peritrófica, necessário para a geração de formas metacíclicas infectantes. As Leishmanias são transmitidas pelos flebótomos que co-injetam parasitas juntamente com a saliva, na derme do hospedeiro. Estudos anteriores demonstraram que a imunização de cães com duas proteínas salivares (LJM17 ou LJL143) de L. longipalpis, resultaram em uma imunidade mediada por células Th1 sistêmica e local afetando a sobrevivência do parasita in vitro. Assim, o objetivo deste trabalho foi avaliar a imunidade conferida pela imunização de cães com DNA e rCanarypoxvirus expressando o gene que codifica para as proteínas salivares de L. longipalpis (LJM17 e/ou LJL143). A imunização com ambas LJL143 e/ou LJM17 induziu uma forte resposta imune humoral. A produção específica do IFN-γ foi observada apenas nas CMSP dos grupos imunizados estimuladas com a proteína. Trinta dias após a última imunização, os cães foram desafiados por via intradérmica com 107 de L. infantum na presença de saliva de L. longipalpis, e a infecção foi detectada no segundo mês após o desafio em todos os grupos. Os cães imunizados com a LJM17 apresentaram maior produção de IFN-γ, IL-2, IL-6, IL-7, IL-15, IL-18, TNF-α, IP-10 e GM-CSF durante a infecção quando comparados com os controles, indicando que o efeito da imunização induzida por LJM17 persistiu mesmo após o desafio. Adicionalmente, diversos estudos realizados no controle da malária, têm demonstrado o uso de antígenos provenientes do vetor para o desenvolvimento de vacinas bloqueadoras de transmissão. Esta estratégia altruísta de imunização visa criar anticorpos que interfiram no desenvolvimento do parasita no interior do vetor. Assim, na segunda etapa do nosso trabalho, foi testada em cães uma estratégia de imunização utilizando uma proteína extraída do intestino médio do L. longipalpis (Luloper1) para induzir a produção de anticorpos em cães saudáveis e infectados e a interrupção da transmissão no flebótomo. Dessa forma, a imunização de cães saudáveis não infectados ou infectados assintomáticos induziu uma potente produção de anticorpos, porém nenhum efeito de bloqueio de transmissão foi detectado em flebótomos alimentados com o sangue desses animais contendo promastigotas de L. infantum.
Sand fly, parasite, host interactions play an important role in the transmission of leishmaniasis. Vector molecules are relevant for such interactions and include midgut and salivary proteins. In vector sand fly species, Leishmania parasites undergo a complex developmental cycle within the midgut, protected by the peritrophic matrix that is necessary for generation of infectious metacyclics. Leishmania parasites are transmitted by sand flies that co-inject parasites and saliva, in the host’s skin. Previous studies showed immunization of dogs with two proteins (LJM17 or LJL143) from Lutzomyia longipalpis, resulted in a systemic and local Th1 cell-mediated immunity affecting parasite survival in vitro. In this work we evaluated the immunity conferredbyimmunization of dogs with DNA and recombinant Canarypoxvírusexpressing the gene encoding the salivary ofL.longipalpis (LJM17and/orLJL143). Immunization with both LJL143 and LJM17 induced a strong specific humoral response. Specific production of IFN-γ was observed only in protein stimulated PBMC immunized groups. Thirty days after last immunization, dogs were challenged intradermally with 107L. infantum in the presence of L. longipalpis saliva and infection was detected in the second month after challenge in all the groups. It was observed that dogs immunized with LJM17 presented higher IFN-γ, IL-2, IL-6, IL-7, IL-15, IL-18, TNF-α, IP-10 and GM-CSF production during infection when compared with controls, indicating that the effect of immunization induced by LJM17 persisted even after challenge. Adittionally, previous studies, mostly with malaria control, have shown the use of several vector antigens for the development of transmission blocking vaccines. This altruist strategy of immunization aims to raise antibodies that could affect the development of the parasite inside the vector. Thus, in the second stage of our work we tested in dogs an immunization using a protein extracted from L. longipalpis midgut (Luloper1) to evaluate antibodies production in healthy and infected dogs and the interruption of transmission in the sand fly. Immunization of either healthy non infected or asymptomatic infected dogs induced a potent antibodies production, but no blocking transmission effect was detect in sand flies fed with blood of these animals containing L. infantum promastigotes
Perez, J. Enrique. "Studies on Lutzomyia spp. vectors of leishmaniasis in Peru." Thesis, University of Liverpool, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.261907.
Повний текст джерелаCotterell, Sarah Elizabeth Jane. "The production and recruitment of leukocytes during murine visceral leishmaniasis." Thesis, London School of Hygiene and Tropical Medicine (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.321966.
Повний текст джерелаRibeiro, Jean Francisco Rosa. "Inibidores de Cisteíno Proteases como Candidatos Terapêuticos para o Tratamento de Doenças Parasitárias." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/75/75133/tde-10102018-160410/.
Повний текст джерелаA necessidade urgente de descoberta de terapias mais seguras e eficazes para o tratamento da doença de Chagas e leishmanioses tem motivado a pesquisa por novos inibidores das enzimas cruzaína e CPB, as principais cisteíno proteases do T. cruzie e Leishmania spp., respectivamente. Uma série de 52 compostos nitrílicos que atuam como inibidores covalente-reversíveis de cisteíno proteases foi sintetizada no grupo NEQUIMED/IQSC/USP e avaliada quanto a sua atividade inibitória contra as enzimas cruzaína, CPB de Leishmania mexicana e catepsina L de humanos. Utilizando planejamento molecular baseado em hipótese, mapeamos as relações estrutura-atividade (SARs) desses inibidores através de variações nas posições P1, P2, P3 e P1\' do esqueleto dipeptidil nitrílico. A substituição do grupo eletrofílico (warhead) aminonitrila em P1 pelo grupo azanitrila melhorou a afinidade em duas ordens de magnitude para todos os alvos avaliados. Um dos mais potentes inibidores, o análogo azanitrila Neq0690 mostrou uma cinética de ligação lenta com valores de pKi de 8,8, 9,3 e 9,7 para cruzaína, catepsina L e LmCPB, respectivamente. A substituição bioisostérica da ligação amida entre as posições P2-P3 pelo grupo trifluoroetilamina resultou na síntese do Neq0659, um potente inibidor com um perfil de ação seletivo para as proteases de parasitos. A substituição do grupo metileno em P1 pelo ciclopropano aumentou a afinidade para todas as enzimas. Contudo, uma inibição seletiva da cruzaína e LmCPB foi associada à presença do grupo (R)-benzila como substituinte da posição P1 dos derivados CF3 substituídos. Embora os compostos substituídos com leucina, tirosina, triptofano e 3-cloro fenilalanina como substituintes da posição P2 foram relativamente bem tolerados pela cruzaína e catepsina L, uma restrita especificidade foi verificada para LmCPB com pequenos ganhos de afinidade para os inibidores que possuíam os grupos leucina e metil benzoato como substituintes dessa posição. Com relação à posição P3, a inserção do grupo 3-terc-butilpirazol e 3-bromo piridina aumentou a afinidade para todos os alvos avaliados enquanto que um ganho seletivo para a LmCPB foi observado para os compostos que possuíam o grupo bifenila nessa posição. Além disso, duas novas estruturas cristalográficas da LmCPB complexada com o Neq0690 e metil metanotiossulfonato (MMTS) foram determinadas com resoluções de 1,3 Å e 1,5 Å, respectivamente. As estruturas dos co-complexos revelaram os modos de interação (MoB) desses ligantes, bem como as principais características do processo de reconhecimento bimolecular. Isso permitirá o uso de estratégias de planejamento baseado na estrutura do alvo com translação natural para a pesquisa por novos inibidores de cisteíno proteases, com amplo espectro de ação na quimioterapia de doenças a elas relacionadas.
The urgent need for the discovery of safer and more effective therapies for the treatment of Chagas disease and leishmaniasis has motivated the search for new inhibitors of the enzymes cruzain and CPB, the major T. cruzi and Leishmania spp. cysteine proteases, respectively. A series of 52 nitrile-containing compounds acting as covalent-reversible inhibitors of cysteine proteases was synthesized at the NEQUIMED/IQSC/USP Medicinal Chemistry Group and evaluated for their inhibitory activity against the enzymes cruzain, Leishmania mexicana CPB and cathepsin L from humans. Using hypothesis-driven molecular design, we mapped the structure-activity relationships (SARs) of these inhibitors through variations in the P1, P2, P3 and P1\' positions of the dipeptidyl nitrile scaffold. The substitution of the aminonitrile by the azanitrile group improved the affinity by two orders of magnitude for all the evaluated targets. One of the most potent inhibitors, the azanitrile analogue dubbed Neq0690 showed a slow-binding kinetics with pKi values of 8.8, 9.3 and 9.7 for cruzain, cathepsin L and LmCPB, respectively. Bioisosteric substitution of the amide moiety between the P2-P3 positions by the trifluoroethylamine group resulted in the synthesis of Neq0659, a potent inhibitor with a selective action profile for parasite proteases. Substitution of the methylene group at P1 by cyclopropane increased the affinity for all enzymes. However, selective inhibition of cruzain and LmCPB was associated with the presence of the (R)-benzyl group as substituent of the P1 position of the substituted CF3 derivatives. Although leucine, tyrosine, tryptophan and 3-chloro phenylalanine substituted compounds as substituents of the P2 position were relatively well tolerated by cruzain and cathepsin L, a restricted specificity was verified for LmCPB with small affinity gains for the inhibitors possessing the leucine and methyl benzoate as substituents of that position. Regarding the P3 position, the insertion of the 3-tert-butylpyrazole and 3-bromo pyridine groups increased the affinity for all evaluated targets whereas a selective gain for LmCPB was observed for the compounds having the biphenyl moiety at that position. In addition, it is noteworthy that two new crystallographic structures of LmCPB complexed with Neq0690 and methyl methanethiosulfonate (MMTS) were determined with resolutions of 1.3 Å and 1.5 Å, respectively. The structures of the co-complexes revealed the modes of binding (MoB) of these ligands, as well as the main characteristics of the bimolecular recognition process. This will allow the natural translational target structure strategies for the search for new inhibitors of cysteine proteases with broad spectrum of action in the chemotherapy of related diseases.
Shimozako, Hélio Junji. "Modelo de otimização para o controle da leishmaniose: análise epidemiológica e econômica." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/5/5144/tde-22012016-085645/.
Повний текст джерелаZoonotic visceral leishmaniasis (ZVL) is one of the most important emerging parasitic diseases. Brazil, in particular, is considered one of the countries in which this disease is most endernic. Despite the publication of visceral leishmaniasis control guidelines and the investment in health services and controljpreventive activities, the vectors and reser- voirs in urban areas are the major challenge for those control programs. This is due to (1) the need for better comprehension regarding the vector behavior in the urban envi- ronment; (2) the operating difficulties in perforrning the activities in time to reach good results; and (3) the high cost of those activities. The main objective of this study was to elaborate an optirnization model for leishmaniasis control. This model is based on 5 con- trol parameters that correspond to the following strategies: (I) vector population control, (11) elirnination of positive dogs, (111) use of insecticide-impregnated dog collars, (IV) dog vaccination and (V) dog treatment. This model was elaborated using an equation system, composed of 17 differential equations, 4 of which represent the disease dynarnic on hu- man population (susceptible (Xh), latent (Ih), clinically ill (Yh) and recovered humans (Zft)), 10 for dog population (susceptible (Xd and xcd), latent (ld and Icd), clinically ill (Yd and Ycd), recovered (Zd and zcd) and vaccinated dogs (Vd and vcd), where C represents the categories using the insecticide-impregnated dog collars) and 3 for vector population (non-infected (SI), infected but not infective (S2), infected and infective sandflies (S3)). For econornic analysis of those control strategies, we estimated the cost of them per dog (in the case of vector control population, it was estimated per treated house). Regarding the nume- rical simulations without the control strategies, the endernic equilibrium densities were: Xh = 0.394, Ih = 0.0305, Yh = 0.00167, Zh = 0.574, Xd = 0.314, Id = 0.165, Yd = 0.0163, Zd = 0.505, SI = 0.709, S2 = 0.0858 and S3 = 0.205. In endernic equilibrium state, the basic reproduction number and the rate of reported human cases per day were estimated as 1%0 = 4.50 and R = 3.58 x 1O-6/day, respectively. Considering the impact evaluation of controI strategies, the vector population control was the strategy that resulted in a fas- ter decrease in the rate of human reported cases per day and, consequently, in the larger reduction of medical and hospital costs too. However, the investment (that is, the cost) of the vector population control was the highest one. On the other hand, the investment in elirninating positive dogs was considered the lowest one. Since those control strategies operate at different points within the epiderniological chain, the planning a control, while taking into account the simultaneous action of these strategies, could not only result in a more interesting control strategy, but could also improve the optirnization of investments on visceralleishmaniasis control
Scaduto, Ryan. "A Natural Product and High-Throughput Screening Synthetic Approach Towards the Discovery of Antileishmanial Agents." Ohio Dominican University Honors Theses / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=oduhonors1620081955401195.
Повний текст джерелаValenta, David Thomas. "The ecology of sandflies (Diptera: Psychodidae), vectors of cutaneous leishmaniasis, in the Andes of Western Venezuela." Thesis, University of London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325477.
Повний текст джерелаYadon, Zaida Estela. "Risk factors for American Cutaneous Leishmaniasis in Santiago del Estero, Argentina : a retrospective case-control study." Thesis, London School of Hygiene and Tropical Medicine (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244042.
Повний текст джерелаSantos, Katia Solange Cardoso Rodrigues dos. "Latenciação de hidroximetilnitrofural com derivados de quitosana, potencialmente ativos em leishmaniose e doença de Chagas." Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/9/9138/tde-05092006-232733/.
Повний текст джерелаLeishmaniasis and Chagas\' disease are endemic parasitosis provoked by the protozoa Leishmania spp and Trypanosoma cruzi, respectively. Due to the scarce chemotherapy, to the high toxicity of the available drugs and to their low effectiveness, mainly in the treatment of intracellular replicant forms of those parasites, the search for new chemotherapeutic alternatives is extremely important. Hydroxymethylnitrofurazone, a nitrofurazone Mannich basis, has proven to be active against trypanomicide before and its activity in cultures of L. amazonensis, L. chagasi and L. braziliensis promastigotes was determined in this work. With the purpose of obtaining prodrugs potentially active in Chagas\' disease and visceral and mucocutaneous leishmaniases, hydrosoluble hydroxymethylnitrofurazone prodrugs have been designed and synthesized using chitosan, a polysaccharide showing immunomudulatory activity, as the carrier. Membranes from chitosan linked with hydroxymethylnitrofurazone have been synthesized for topical administration in cutaneous leishmaniasis. Membranes were obtained by graft copolymerization of hydroxyethy/methacrylate and acrylic acid onto chitosan and their biocompatibility - trombogenicity, citotoxicity and hemolysis potential - was evaluated. Those membranes with higher content of hydroxyethylmethacrylate showed to be neither cytotoxic nor hemolytic; those with higher content of acrylic acid showed good swelling properties, although a certain level of cytotoxicity and haemolysis has been detected, due to the presence of non-reacted monomers. The linkage of hydroxymethylnitrofurazone to chitosan by a succinyl spacer group led to a prodrug with filmogenic properties for topic administration. The derivatives obtained - prodrugs and carriers (modified chitosans) - were analyzed by infrared, nuclear magnetic resonance (1H NMR and 13C NMR) and by thermal analysis - DMTA, TG and DSC. Tests of trypanomicide and leishmanicide activity with polymer prodrugs and membranes will be further developed.
G, Tassone. "Structural studies on human and parasite enzymes related to disease." Doctoral thesis, Università di Siena, 2019. http://hdl.handle.net/11365/1070917.
Повний текст джерелаSteinkamp, Heidi Marie. "The Role of Macrophages and the Th1 Transcription Factors STAT1 and STAT4 During Visceral Leishmaniasis." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1338335780.
Повний текст джерелаJagadesh, Soushieta. "Biogeography of Emerging Infectious Diseases In search for the hotspots of Disease X: A biogeographic approach to mapping the predictive risk of WHO’s Blueprint Priority Diseases Emerging human infectious diseases of aquatic origin: a comparative biogeographic approach using Bayesian spatial modelling Global emergence of Buruli Ulcer Spatial variations between Leishmania species: A biogeographic approach to mapping the distribution of Leishmania species in French Guiana Mapping priority neighborhoods: A novel approach to cluster identification in HIV/AIDS population." Thesis, Guyane, 2020. http://www.theses.fr/2020YANE0007.
Повний текст джерелаThe COVID-19 pandemic highlights that the spread of infectious diseases goes beyond geographical boundaries. Simultaneous changes in local biodiversity and land use, the increasing international connectivity through human transport and trade and the imminent threat of climate change have increased the risk of the emergence and reemergence of infectious diseases. The current public health response to emerging infectious diseases (EID) by passive surveillance has proven largely ineffective in preventing and controlling disease outbreaks. The way toward is to “get ahead of the curve” by identifying potential hotspots of disease emergence and detecting the environmental triggers such as land transformation, biodiversity loss and climate change. I used a biogeographic approach to study and analyze disease emergence across different taxonomic pathogen groups such as bacterial, viral, protozoal and fungal, globally and in French Guiana, a French Overseas territory located in South America. I found that regions at risk of floods, recent conversion of forest to agricultural lands and increasing minimum temperature (i.e. temperature at night) caused by cli mate change were drivers for disease emergence locally and globally across the different pathogen groups. The main findings of the PhD thesis are the following:1. Biogeographic approach to mapping the distribution of EIDs with using existing human cases data, remote sensing imagery and unconventional statistical models is effective to “get ahead of the curve” in the detection of regions at risk and the management of EIDs.2. EIDs are not unprecedented but predictable by identifying and managing the triggers of disease emergence, which have a direct link with the anthropization of the environment
Singh, Jasdeep. "molecular target based lead identification against leishmaniasis and protein aggregation disorders." Thesis, 2018. http://localhost:8080/xmlui/handle/12345678/7638.
Повний текст джерелаIverson, Chad. "Identification of glutathione S-transferase inhibiting natural products from Matricaria chamomilla and biotransformation studies on oxymatrine and harmine." 2010. http://hdl.handle.net/1993/4150.
Повний текст джерелаMendes, Mafalda Maria Teixeira. "Relatórios de Estágio e Monografia intitulada "Nanotecnologia no Tratamento e Diagnóstico de Doenças Causadas por Tripanossomatídeos"." Master's thesis, 2021. http://hdl.handle.net/10316/99086.
Повний текст джерелаO estágio curricular e a realização da dissertação de mestrado representam o culminar dos últimos cinco anos de experiências e aquisição de conhecimentos. Os relatórios elaborados, sob a forma de uma análise SWOT, visam uma avaliação das experiências vividas, competências e conhecimentos adquiridos durante os respetivos estágios em Farmácia Comunitária e Indústria Farmacêutica. Adicionalmente, a dissertação apresentada realizou-se no âmbito do tema “Nanotecnologia no Tratamento e Diagnóstico de Doenças Causadas por Tripanossomatídeos”. Nas últimas décadas, a nanotecnologia tem vindo a mostrar-se vital para o desenvolvimento da indústria farmacêutica, no âmbito das técnicas de tratamento e diagnóstico. A escala nanométrica traz consigo soluções inovadoras, para a incorporação, transporte e entrega dos fármacos e substâncias ativas convencionalmente usados na prática clínica. A melhoria significativa de aspetos como a solubilidade, biodisponibilidade e tempo de retenção dos fármacos, bem como a diminuição da toxicidade de medicação convencional, tornam o uso da nanotecnologia bastante apetecível. Atualmente, encontram-se em estudos in vitro e in vivo uma série de nanomedicamentos, sob diferentes formas, tais como nanopartículas, nanolipossomas e nanoconjugados, existindo já formulações com sucesso comercial. A nanotecnologia no tratamento e diagnóstico de doenças parasitárias tem sido alvo de grande atenção e estudo, uma vez que os regimes terapêuticos disponíveis nesta área são bastante complexos e morosos, tendo associado um elevado risco de toxicidade. Doenças como a leishmaniose, doença de chagas e doença do sono, abordadas nesta monografia, são exemplos claros de infeções que beneficiam das soluções proporcionadas pela nanotecnologia. Estudos de formulação de nanossistemas aplicados ao tratamento destas doenças têm-se mostrado eficazes, demonstrando resultados animadores.
The time of the curricular internship and the writing of the master thesis represent the end of the last five years of learning experiences. The following internship reports aim to evaluate by means of a SWOT analysis the experience, acquired skills and know-how obtained during the internships conducted in community pharmacy and pharmaceutical industry. Additionally, the presented monograph elaborates on the theme “Nanotechnology applied to the Treatment and Diagnostics of Diseases Caused by Trypanosomatids”. In the last decades, nanotechnology has shown to be crucial for the development of the pharmaceutical industry, regarding new treatment and diagnosis techniques. Working at the nanoscale has brought new groundbreaking solutions for drug transport and delivery in regard to the drugs already used in clinic. It significantly improves aspects such as solubility, bioavailability and retention time, whilst decreasing toxicity, which makes the use of nanotechnology very appealing. Currently, there are various nanomedicines going through in vitro and in vivo studies. This medicines are presented in forms such as nanoparticles, nanolipossomes or nanoconjugates, some of which already available in the market. Nanotechnology applied to the treatment of parasitic diseases has been given much attention in the last decades, as the available therapeutic regimens in this area are complex and cumbersome, with high toxicity levels. Parasitic diseases such as leishmaniasis, chagas disease and sleeping sickness are clear examples of infections that will benefit from the incorporation of nanotechnology. Studies on nanosystem formulation have proven nanomedicine to be an effective treatment method and the results have been uplifting.