ABSTRACT
BACKGROUND: Schistosomiasis is a neglected tropical disease caused by Schistosoma and affects over 240 million people worldwide. One of the most prominent causative agents is Schistosoma mansoni, which develops inside the intermediate host. Biomphalaria tenagophila is the second most important vector of schistosomiasis in Brazil and the Taim population is completely resistant to infection by S. mansoni. OBJECTIVE: This study aims to identify and characterize B. tenagophila microRNAs (miRNAs) and evaluate their differential expression in S. mansoni-susceptible and -resistant populations of B. tenagophila. METHODS: Two populations of B. tenagophila snails, susceptible and resistant to S. mansoni infection, were used to investigate the small RNA response of these snails after being infected with the parasite. Small RNA sequencing and quantitative real-time PCR were employed to identify and validate differentially expressed miRNAs. Bioinformatics analysis were performed to identify miRNA precursors and mature and evaluate their differential expression. FINDINGS: The study predicted 173 mature miRNAs and 123 precursors. Among them were six Lophotrochozoa-specific miRNAs, three mollusk-specific miRNAs, and six pre-miRNAs in a cluster. The small RNA sequencing and RT-PCR of B. tenagophila samples allowed assessing the expression patterns of miRNAs. MAIN CONCLUSIONS: The results obtained may support future studies in Biomphalaria spp., generating a global impact on disease control.
Subject(s)
Biomphalaria , MicroRNAs , Humans , Animals , Biomphalaria/genetics , MicroRNAs/genetics , Schistosoma mansoni/genetics , Brazil , Computational BiologyABSTRACT
The alkylaminoalkanethiosulfuric acids (AAATs) are amphipathic compounds effective against experimental schistosomiasis, of low toxicity, elevated bioavailability after a single oral dose and prompt tissue absorption. OBJECTIVES: To explore the in-vitro antileishmanial potential of AAATs using five compounds of this series against Leishmania (Viannia) braziliensis. METHODS: Their effects on promastigotes and axenic amastigotes, and cytotoxicity to macrophages were tested by the MTT method, and on Leishmania-infected macrophages by Giemsa stain. Effects on the mitochondrial membrane potential of promastigotes and axenic amastigotes and DNA of intracellular amastigotes were tested using JC-1 and TUNEL assays, respectively. KEY FINDINGS: The 2-(isopropylamino)-1-octanethiosulfuric acid (I) and 2-(sec-butylamino)-1-octanethiosulfuric acid (II) exhibit activity against both promastigotes and intracellular amastigotes (IC50 25-35 µm), being more toxic to intracellular parasites than to the host cell. Compound I induced a loss of viability of axenic amastigotes, significantly reduced (30%) the mitochondrial membrane potential of both promastigotes and axenic amastigotes and promoted selective DNA fragmentation of the nucleus and kinetoplast of intracellular amastigotes. CONCLUSIONS: In this previously unpublished study of trypanosomatids, it is shown that AAATs could also exhibit selective antileishmanial activity, a new possibility to be investigated in oral treatment of leishmaniasis.
Subject(s)
Antiprotozoal Agents/pharmacology , Leishmania braziliensis/isolation & purification , Leishmaniasis/drug therapy , Sulfuric Acids/pharmacology , Administration, Oral , Animals , Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/chemistry , Inhibitory Concentration 50 , Leishmania braziliensis/drug effects , Membrane Potential, Mitochondrial/drug effects , Mice , Mice, Inbred BALB C , Structure-Activity Relationship , Sulfuric Acids/administration & dosage , Sulfuric Acids/chemistryABSTRACT
This paper discusses the development of a series of sulfur-containing compounds that show an interesting in vivo activity against infection by Schistosoma mansoni. These substances include the aminoalkanethiols, aminoalkanethiosulfuric acids and aminoalkyl disulfides, among others. Although the aminoethanethiols and their disulfide derivatives have presented a relatively high toxicity for the host animal, the aminoalkanethiosulfuric acids have a low toxicity and a high specificity for the adult female S. mansoni worms. In vitro studies with schistosomula, lung-phase schistosomula and adult worms have demonstrated effects on the tegument and the metabolism on these different stages of S. mansoni worms. The encapsulation of these drugs in a nanoemulsion has resulted in an increase in the in vitro activity.
Subject(s)
Antiprotozoal Agents/toxicity , Antiprotozoal Agents/therapeutic use , Schistosoma mansoni/drug effects , Schistosomiasis mansoni/drug therapy , Sulfur Compounds/toxicity , Sulfur Compounds/therapeutic use , Animals , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/pharmacology , Female , Humans , Mice , Sulfur Compounds/chemistry , Sulfur Compounds/pharmacologyABSTRACT
BACKGROUND: A 40-year-old female laboratory technician accidentally came into contact with water that contained snails shedding Schistosoma mansoni cercariae while she was maintaining an aquarium. Several minutes after exposure to the contaminated water, she experienced severe itching in the area of exposure, and several papules were observed. INVESTIGATIONS: Taking of medical history to provide evidence of accidental contact with water contaminated with S. mansoni cercariae; physical examination; and stool examinations by the Kato-Katz, formol-ether concentration and sedimentation methods carried out four times weekly, starting 45 days after infection and continuing until 10 weeks after infection. DIAGNOSIS: S. mansoni infection. MANAGEMENT: A single oral dose of 50 mg/kg oxamniquine on the day of the incident.
