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 CABSTRACT
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/cytologyABSTRACT
Abstract: Visceral leishmaniasis (VL) is one of the most important tropical diseases worldwide. Although chemotherapy has been widely used to treat this disease, problems related to the development of parasite resistance and side effects associated with the compounds used have been noted. Hence, alternative approaches for VL control are desirable. Some methods, such as vector control and culling of infected dogs, are insufficiently effective, with the latter not ethically recommended. The development of vaccines to prevent VL is a feasible and desirable measure for disease control; for example, some vaccines designed to protect dogs against VL have recently been brought to market. These vaccines are based on the combination of parasite fractions or recombinant proteins with adjuvants that are able to induce cellular immune responses; however, their partial efficacy and the absence of a vaccine to protect against human leishmaniasis underline the need for characterization of new vaccine candidates. This review presents recent advances in control measures for VL based on vaccine development, describing extensively studied antigens, as well as new antigenic proteins recently identified using immuno-proteomic techniques.
Subject(s)
Humans , Animals , Dogs , Antibodies, Protozoan/immunology , Protozoan Vaccines/immunology , Leishmania/immunology , Leishmaniasis, Visceral/prevention & control , Antigens, Protozoan/immunology , Protozoan Proteins/immunology , Leishmania/classificationABSTRACT
Phage display is a high-throughput subtractive proteomic technology used for the generation and screening of large peptide and antibody libraries. It is based on the selection of phage-fused surface-exposed peptides that recognize specific ligands and demonstrate desired functionality for diagnostic and therapeutic purposes. Phage display has provided unmatched tools for controlling viral, bacterial, fungal, and parasitic infections, and allowed identification of new therapeutic targets to treat cancer, metabolic diseases, and other chronic conditions. This review presents recent advancements in serodiagnostics and prevention of leishmaniasis -an important tropical parasitic disease- achieved using phage display for the identification of novel antigens with improved sensitivity and specificity. Our focus is on theranostics of visceral leishmaniasis with the aim to develop biomarker candidates exhibiting both diagnostic and therapeutic potential to fight this important, yet neglected, tropical disease.
.Subject(s)
Animals , Humans , Mice , Biomarkers , Cell Surface Display Techniques/methods , Leishmaniasis/diagnosis , Leishmaniasis/therapy , Vaccination , Biotechnology , Drug Discovery/methods , Genetic Techniques , Immunotherapy/methods , Leishmaniasis/immunology , Mice, Inbred BALB CABSTRACT
Leishmaniasis is one of the six major tropical diseases targeted by the World Health Organization. It is a life-threatening disease of medical, social and economic importance in endemic areas. No vaccine is yet available for human use, and chemotherapy presents several problems. Pentavalent antimonials have been the drugs of choice to treat the disease for more than six decades; however, they exhibit high toxicity and are not indicated for children, for pregnant or breastfeeding women or for chronically ill patients. Amphotericin B (AmpB) is a second-line drug, and although it has been increasingly used to treat visceral leishmaniasis (VL), its clinical use has been hampered due to its high toxicity. This review focuses on the development and in vivo usage of new delivery systems for AmpB that aim to decrease its toxicity without altering its therapeutic efficacy. These new formulations, when adjusted with regard to their production costs, may be considered new drug delivery systems that promise to improve the treatment of leishmaniasis, by reducing the side effects and the number of doses while permitting a satisfactory cost-benefit ratio.
Subject(s)
Animals , Dogs , Humans , Amphotericin B/administration & dosage , Antiprotozoal Agents/administration & dosage , Drug Delivery Systems , Leishmaniasis, Visceral/drug therapy , Chemistry, Pharmaceutical , Nanoparticles , NanotechnologyABSTRACT
A frequência de grupos sanguíneos dos sistemas ABO e Rh são variáveis entre as diversas populações do mundo. No período de 1999 a 2007, no Setor de Patologia Clínica do Colégio Técnico da UFMG foi realizada a tipagem sanguínea nos sistemas ABO e Rh em uma amostra populacional representada por 4800 pessoas por meio de coleta de amostras de sangue por punção digital e/ou coleta venosa, de indivíduos residentes em Belo Horizonte e sua região metropolitana. Os resultados revelaram uma frequência média de 38% para o grupo sanguíneo do tipo A; 12% para o grupo B, 4% para o grupo AB e 46% para o grupo O. Na determinação de fator Rh a frequência encontrada foi de 93% para o grupo Rh+ e 7% para Rh-. Dessa forma, por meio de uma amostragem significativa populacional, observou-se que o tipo sanguíneo O/Rh+ é o mais encontrado em Belo Horizonte e região metropolitana.
Subject(s)
Humans , ABO Blood-Group System , Epidemiologic Studies , Rh-Hr Blood-Group SystemABSTRACT
O infarto agudo do miocárdio e a angina de peito constituem patologias associadas a uma ativaçäo exacerbada do mecanismo da coagulaçäo. As plaquetas e o fibrinogênio consistem em importantes elementos na composiçäo do coágulo de fibrina. Uma atividade plaquetária aumentada e níveis plasmáticos elevados de fibrinogênio podem se constituir em importantes fatores para a ocorrência das doenças coronarianas. Objetivo: Investigar se o aumento gradual da atividade plaquetária, medida pelo teste da agregaçäo plaquetária, e dos níveis plasmáticos de fibrinogênio é compatível com os diferentes estágios de desenvolvimento das doenças coronarianas. Material e método: Foram avaliados pacientes com infarto agudo do miocárdio (n=11), angina de peito (n=8), indivíduos com fatores de risco para desenvolver estas doenças, porém ainda assintomáticos (n=16), além de voluntários aparentemente saudáveis (n=10), como controle. Resultados: Os níveis de fibrinogênio se apresentaram significativamente elevados nos grupos de pacientes com doenças coronarianas, comparados aos grupos de controle e dos indivíduos com fatores de risco (p < 0,005). A agregaçäo plaquetária se mostrou significativamente elevada e com resultados similares nos grupos de pacientes com doenças coronarianas e de risco em comparaçäo com o grupo-controle (p < 0,001). Discussäo: A agregaçäo plaquetária já se mostrou significativamente aumentada no grupo de risco em relaçäo ao grupo-controle, indicando ser um parâmetro que se altera precocemente. Conclusöes: Os achados laboratoriais indicam que os níveis de fibrinogênio se mostraram um parâmetro significativamente elevado nos pacientes com doenças coronarianas, enquanto o teste da agregaçäo plaquetária parece ser útil como um parâmetro preditivo de risco para doença coronariana