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

The Epstein-Barr virus (EBV), which infects over 90% of adults, appears to have evolved to exploit the normal biology of B-cell development in order to persist as a life-long asymptomatic infection. However, EBV can contribute to oncogenesis. It has become evident that alterations in the expression of microRNAs (miRNAs) from the host cell and EBV can also contribute to cancer pathogenesis. MicroRNAs function by inhibiting translation of select groups of mRNA transcripts containing imperfect annealing sequences in their 3' untranslated regions (3' UTRs) and less frequently through other regions of the transcript. A number of studies have demonstrated that profiles of miRNA expression could establish phenotypic signatures of different cancer types where viruses have been evolved with highly sophisticated gene silencing machinery to disturb the host-immune response. Based on current review, it is possible that a specific virus miRNA may be involved in cancer pathogenesis.

Paracoccidioidomycosis (PCM) is a granulomatous disease caused by a dimorphic fungus, Paracoccidioides brasiliensis (Pb). To determine the influence of nitric oxide (NO) on this disease, we tested cis-[Ru(bpy)2(NO)SO3](PF6), ruthenium nitrosyl, which releases NO when activated by biological reducing agents, in BALB/c mice infected intravenously with Pb 18 isolate. In a previous study by our group, the fungicidal activity of ruthenium nitrosyl was evaluated in a mouse model of acute PCM, by measuring the immune cellular response (DTH), histopathological characteristics of the granulomatous lesions (and numbers), cytokines, and NO production. We found that cis-[Ru(bpy)2(NO)SO3](PF6)-treated mice were more resistant to infection, since they exhibited higher survival when compared with the control group. Furthermore, we observed a decreased influx of inflammatory cells in the lung and liver tissue of treated mice, possibly because of a minor reduction in fungal cell numbers. Moreover, an increased production of IL-10 and a decrease in TNF-α levels were detected in lung tissues of infected mice treated with cis-[Ru(bpy)2(NO)SO3](PF6). Immunohistochemistry showed that there was no difference in the number of VEGF- expressing cells. The animals treated with cis-[Ru(bpy)2(NO)SO3](PF6) showed high NO levels at 40 days after infection. These results show that NO is effectively involved in the mechanism that regulates the immune response in lung of Pb-infected mice. These data suggest that NO is a resistance factor during paracoccidioidomycosis by controlling fungal proliferation, influencing cytokine production, and consequently moderating the development of a strong inflammatory response.