Nitric oxide (NO) is a free radical synthesized from L-arginine by different isoforms NO-synthases. NO possesses multiple and complex biological functions. NO is an important mediator of homeostasis, and changes in its generation or actions can contribute or not to pathological states. The knowledge of effects of NO has been not only important to our understanding of immune response, but also to new tools for research and treatment of various diseases. Knowing the importance of NO as inflammatory mediator in diverse infectious diseases, we decided to develop a revision that shows the participation/effect of this mediator in immune response induced against Giardia spp. Several studies already demonstrated the participation of NO with microbicidal and microbiostatic activity in giardiasis. On the other hand, some works report that Giardia spp. inhibit NO production by consuming the intermediate metabolite arginine. In fact, studies in vitro showed that G. lamblia infection of human intestinal epithelial cells had reduced NO production. This occurs due to limited offer of the crucial substrate arginine (essential aminoacid for NO production), consequently reducing NO production. Therefore, the balance between giardial arginine consumption and epithelial NO production could contribute to the variability of the duration and severity of infections by this ubiquitous parasite.

Caryocar coriaceum fruits, found in Brazilian Cerrado and Caatinga, are commonly used as food and in folk medicine, as anti-inflammatory, bactericide, fungicide, leishmanicide, and nematicide. Due to the biological potential of this plant, this study focuses on the evaluation of antifungal and antileishmanial activities, including anticholinesterase and antioxidant tests, correlating with total phenols and flavonoids content. Peel extracts contain higher yield of phenols and flavonoids as analyzed by spectrophotometric methods. HPLC analysis of flavonoids revealed that isoquercitrin is the main flavonoid in both parts of the fruit, and peel extract showed the best antioxidant activity. In the inhibition of the acetylcholinesterase assay, both extracts demonstrate action comparable to physostigmine. The antimicrobial activity of extracts was evaluated against strains of Malassezia sp. and Microsporum canis, using the broth microdilution technique, in which the extracts showed similar MIC and MFC. The extracts present antileishmanial activity and low toxicity on murine macrophages and erythrocytes. Therefore, these results suggest a potential for the application of C. coriaceum fruit's ethanol extracts in the treatment against dermatophyte fungi and leishmaniasis, probably due to the presence of active flavonoids. Further in vivo studies are recommended aiming at the development of possible new pharmaceutical compounds.

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Leishmania amazonensis (L. amazonensis) infection can cause severe local and diffuse injuries in humans, a condition clinically known as American cutaneous leishmaniasis (ACL). Currently, the therapeutic approach for ACL is based on Glucantime, which shows high toxicity and poor effectiveness. Therefore, ACL remains a neglected disease with limited options for treatment. Herein, the in vitro antiprotozoal effect and mechanisms of the diterpene kaurenoic acid [ent-kaur-16-en-19-oic acid] (KA) against L. amazonensis were investigated. KA exhibited a direct antileishmanial effect on L. amazonensis promastigotes. Importantly, KA also reduced the intracellular number of amastigote forms and percentage of infected peritoneal macrophages of BALB/c mice. Mechanistically, KA treatment reestablished the production of nitric oxide (NO) in a constitutive NO synthase- (cNOS-) dependent manner, subverting the NO-depleting escape mechanism of L. amazonensis. Furthermore, KA induced increased production of IL-1β and expression of the inflammasome-activating component NLRP12. These findings demonstrate the leishmanicidal capability of KA against L. amazonensis in macrophage culture by triggering a NLRP12/IL-1β/cNOS/NO mechanism.

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O objetivo deste estudo foi investigar a prevalência de enteroparasitoses e os fatores envolvidos na transmissão de enteroparasitoses em crianças de 0 a 15 anos de idade do município de São Jerônimo da Serra, Paraná. O trabalho foi desenvolvido no período de julho de 2014 a junho 2017. Analisou-se 362 amostras pelos métodos de Hoffman, Pons e Janer e Faust e cols. As associações entre variáveis socioeconômicas, referentes aos hábitos das crianças e ao ambiente em que vivem e enteroparasitoses foram verificadas por meio de regressão logística, considerado nível de significância de 5%. Encontrou-se alta prevalência de parasitismo (36,5%), uma alta frequência de poliparasitismo (43,9%) e uma freqüência maior de protozoários (34,5%) em relação aos helmintos (3,9%). Os enteroparasitas patogênicos encontrados foram Giardia lamblia (8,0%), Entamoeba histolytica/dispar (3,6%), Hymenolepis nana (2,5%), Enterobius vermicularis (2,2%), Ascaris lumbricoides (1,1%), ancilostomídeos (0,8%) e Trichuris trichiura (0,3%). Endolimax nana foi o mais frequentemente encontrado (19,3%). Mesmo sendo comensal, sua detecção é preocupante uma vez que o mecanismo de transmissão (fecal-oral) é igual dos microrganismos patogênicos. Observou-se associação entre a presença de enteroparasitoses e faixa etária, renda familiar, escolaridade dos responsáveis, morar em zona rural, consumo de água não tratada, destino inadequado do lixo, contato com areia ou terra e presença de um animal de estimação. Hábitos de higiene, condições sanitárias, socioeconômicas e sociodemográficas estão diretamente relacionados às infecções por parasitos intestinais e devem ser melhoradas para evitar disseminação na população

ResumoA leishmaniose causa mortalidade e morbidade em mais de 80 países e caracteriza-se como uma doença parasitária com diversas manifestações, por isso constitui um sério problema de saúde pública. No Novo Mundo ocorre a Leishmaniose Visceral (LV) e Leishmaniose Tegumentar Americana (LTA). A LTA é considerada uma enfermidade polimórfica, espectral da pele e das mucosas, agrupada em diferentes formas clínicas: a leishmaniose cutânea, a cutaneomucosa e a cutânea difusa. A Organização Mundial da Saúde recomenda os antimoniais pentavalentes como drogas de primeira escolha no tratamento da leishmaniose. Entretanto, devido aos efeitos indesejados dessas drogas, tem sido proposto o estudo para o desenvolvimento de novos fármacos para seu tratamento. Assim, tem-se investigado o uso da própolis, visto que está relacionada a muitas atividades biológicas, como antibacteriana, antifúngica, antiulcerativa, antiviral, antiprotozoária, antiinflamatória, hepatoprotetora, antioxidante, antitumoral, entre outras. Estudos recentes mostraram que a própolis verde ativa macrófagos e estimula os linfócitos B a produzirem anticorpos. A própolis tem demonstrado potencial atividade leishmanicida, por diminuir o diâmetro das lesões, causar alterações morfológicas nas formas promastigotas ou ainda por melhorar a resposta imunológica frente às Leishmanias, ativando macrófagos.Portanto, o objetivo deste trabalho foi relatar as principais atividades leishmanicidas da própolis, por meio de pesquisa bibliográfica eletrônica no PubMed e Scielo durante o ano de 2009 Palavras-chave: Leishmaniose. Própolis. Ação antiprotozoária.Leishmaniasis is a public health problem causing morbidity and mortality in over 80 countries and features a parasitic disease with several manifestations. In the New World occur Visceral Leishmaniasis (VL) and American Cutaneous Leishmaniasis (ACL). The ACL is considered a disease polymorphic of skin and mucous membranes, grouped in different clinical forms: cutaneous leishmaniasis in the skin and mucosa and diffuse cutaneous, and the evolution of this disease is closely related to the mechanisms of escape of the protozoan Leishmania from the immune response, allowing the development of the disease and consequently the onset of clinical manifestations known. The World Health Organization recommends the pentavalent antimony as the first choice drugs. However, they usually give unsatisfactory results, requiring the development of new and affordable drugs for its treatment. It has been investigated that use of propolis it is related to exhibit several biological activities such as antibacterial, antifungal,

Leishmaniasis is a neglected tropical disease caused by Leishmania species. Available therapeutic options have several limitations. The drive to develop new, more potent, and selective antileishmanial agents is thus a major goal. Herein we report the synthesis and the biological activity evaluation against promastigote and amastigote forms of Leishmania amazonensis of nine 4,8-dimethoxynaphthalenyl chalcones. Compound ((E)-1-(4,8-dimethoxynaphthalen-1-yl)-3-(4-nitrophenyl)prop-2-en-1-one), 4f, was the most promising with an IC50 = 3.3 ± 0.34 μM (promastigotes), a low cytotoxicity profile (CC50 = 372.9 ± 0.04 μM), and a high selectivity index (SI = 112.6). Furthermore, 4f induced several morphological and ultrastructural changes in the free promastigote forms, loss of plasma membrane integrity, and increased reactive oxygen species (ROS). An in silico analysis of drug-likeness and ADME parameters suggested high oral bioavailability and intestinal absorption. Compound 4f reduced the number of infected macrophages and the number of amastigotes per macrophage, with an IC50 value of 18.5 ± 1.19 μM. Molecular docking studies with targets, ARG and TR, showed that compound 4f had more hydrogen bond interactions with the ARG enzyme, indicating a more stable protein-ligand binding. These results suggest that 4,8-dimethoxynaphthalenyl chalcones are worthy of further study as potential antileishmanial drugs.