ABSTRACT
Quinoxaline derivatives are reported as antineoplastic agents against a variety of human cancer cell lines, with some compounds being submitted to clinical trials. In this work, we report the synthesis, characterization and cytotoxicity potential of a new series of quinoxalinyl-hydrazones. The most cytotoxic compound was (E)-2-[2-(2-pyridin-2-ylmethylene)hydrazinyl]quinoxaline (PJOV56) that presented a time-dependent effect against HCT-116 cells. After 48 h of incubation, PJOV56 was able to induce autophagy and apoptosis of HCT-116 cells, mediated by upregulation of Beclin 1, upregulation of LC3A/B II and activation of caspase 7. Apoptosis was induced along with G0/G1 cell cycle arrest at the highest concentration of PJOV56 (6.0 µM). Thus, PJOV56 showed a dose-dependent mode of action related to induction of autophagy and apoptosis in HCT-116 cells.
Subject(s)
Apoptosis/drug effects , Autophagy/drug effects , Colorectal Neoplasms/drug therapy , Hydrazones/chemical synthesis , Quinoxalines/chemical synthesis , Humans , Hydrazones/chemistry , Quinoxalines/chemistry , Structure-Activity RelationshipABSTRACT
Introduction: Immunoglobulins, soluble antigens, cells, cytokines and other immune system products can be transferred from infected mother to her offspring, leading to suppression or stimulation of immune response. Objective: To evaluate the influence of gender and maternal infection with Leishmania braziliensis in the course of the disease in the offspring of hamsters. Methods: Offspring born from infected mother (IMO) or non-infected mother (NIMO) by Leishmania braziliensis, both sexes, was infected with the same strain of the mother after 30 days of life and followed for 18 weeks. We evaluated the thickness of the lesion, parasite load and histology of the lesions. Results: The number of parasite in both lesions and lymph node of IMO offspring showed a significant reduction in the 5th week post-infection compared to the NIMO offspring; however, this did not correspond to clinical symptoms. Histopathological analysis revealed that in the IMO offspring, the inflammatory process was more prominent. In relation to gender, it was observed that the male offspring showed lesion thickness and higher parasite burden than females. Conclusion: Maternal infection by L. braziliensis in hamsters does not appear to influence the course of the disease in the homologous offspring infection, as well as the male offspring presented augmented susceptibility to L. braziliensis infection regardless of whether they were born from IMO or NIMO. Also, the reduction of the granuloma index in the IMO offspring, together with the higher inflammatory response, suggests a less effective cellular response in the chronic phase of the disease in these animals. (AU)
Introdução: Imunoglobulinas, antígenos solúveis, células, citocinas e outros produtos do sistema imune podem ser transferidos de mãe infectada para a sua prole, levando à supressão ou estimulação da resposta imune. Objetivo: Avaliar a influência do gênero e a infecção materna por Leishmania braziliensis no curso da doença na prole de hamsters. Métodos: Filhotes nascidos de mãe infectada (MI) e mãe não infectada (MNI) por L. braziliensis, ambos os sexos, foram infectados com a mesma cepa da mãe após 30 dias de vida e acompanhados por 18 semanas. Avaliou-se a espessura da lesão, a carga parasitária e os aspectos histopatológicos das lesões. Resultados: A carga parasitária (lesões e linfonodo de drenagem das lesões) da prole nascida de MI mostrou diminuição significativa na 5a semana pós-infecção, comparada àquela nascida de MNI, no entanto, esta diminuição não correspondeu aos sintomas clínicos. A análise histopatológica revelou que na prole nascida de MI, o processo inflamatório mostrou-se mais proeminente. Em relação ao gênero observou-se que os filhotes machos apresentaram espessura das lesões e carga parasitária maiores do que as fêmeas. Conclusão: A infecção materna por L. braziliensis parece não influenciar o curso da doença na infecção homóloga da prole, bem como os filhotes machos apresentaram aumentada susceptibilidade à infecção por L. braziliensis, independente se eles nasceram de MI ou MNI. Além disso, a redução no index de granulomas na prole nascida de MI, em conjunto com a maior resposta inflamatória, sugere uma resposta celular menos efetiva na fase crônica da doença nestes animais. (AU)
Subject(s)
Leishmania braziliensis , Cricetinae , InfectionsABSTRACT
Leptospirosis is a febrile disease with a typically underestimated global incidence, especially in regions where dengue is endemic. Therefore, it is difficult to accurately determine the number of leptospirosis cases in these areas, which contributes to significant under-reporting this disease. In this study, we estimated the number of possible leptospirosis cases among dengue-like cases that were reported during 2008, 2010, and 2012 in the city of Fortaleza, northeast Brazil. Patients were evaluated for dengue and leptospirosis using immunoenzymatic tests for IgM antibodies that were specific to each pathogen. Among the suspected cases of dengue that resulted as negative in laboratory tests, 10.8% (2008), 19.2% (2010), and 30.8% (2012) were confirmed to be leptospirosis. Considering the cases reported by the surveillance authority as dengue that were subsequently discarded based on the laboratory test results, we estimate that the number of actual leptospirosis cases may be 26 to 49 times higher than those diagnosed and reported by the Health Services. Furthermore, we believe that approximately 20% of dengue-like cases may be leptospirosis cases in areas where the two diseases are endemic.
