•Eighteen cases of Chagas disease were confirmed serologically in the semiarid region of Rio Grande do Norte state, Brazil, with two deaths reported.•Only 7.5% of residents in the outbreak area ...admitted knowledge that Chagas disease can also be acquired orally;.•Twelve percent of dwellings were found to be suitable for triatomine colonization;.•Thirteen percent of people reported they may have been bitten by triatomines in the last three years;.•The physical proximity between humans and triatomine populations with high trypanosoma cruzi prevalence represents a risk factor to further oral/vector contaminations.
Chagas disease is a neglected tropical disease strongly associated with low socioeconomic status, affecting nearly 8 million people – mainly Latin Americans. The current infection risk is based on acute case reports, most of which are typically associated with oral transmissions. In the semi-arid region of Northeastern Brazil, serious outbreaks of this transmission type have surged in the last years. One of those occurred in 2016 in the state of Rio Grande do Norte. Rural residents of four municipalities surrounding Marcelino Vieira ingested sugar cane juice – which was probably ground with Trypanosoma cruzi-infected insects. Eighteen cases of Chagas disease were confirmed serologically, with two deaths reported. Socioeconomic information, schooling of residents and the structure of peridomestic and domestic environments in the rural area of Marcelino Vieira, along with entomological indicators, were investigated to understand better the factors related to the outbreaks in this region. We found triatomines (mainly Triatoma brasiliensis) in 35% (24/67) of domiciliary units and all rocky outcrops inspected (n = 7). Overall, 25% (91/357) of examined T. brasiliensis were infected by T. cruzi in artificial ecotopes, with almost the same prevalence in the sylvatic environment (22%; 35/154). Among all ecotopes investigated, wood/tile/brick piles were the ones linked to high insect infestations and triatomine T. cruzi infection prevalence. Ninety-five percent of people interviewed recognized the triatomines and knew the classic route of transmission of disease – triatomine bite-dependent. However, only 7.5% admitted knowledge that Chagas disease can also be acquired orally – which poses a risk this transmission route currently recognized. Here, we highlight the physical proximity between humans and triatomine populations with high T. cruzi infection prevalence as an additional risk factor to oral/vector contaminations. In sum, residents have low income, low level of education, and/or a willful disregard for the routes of Chagas disease transmission (specifically oral transmission), a combination of factors that may have favored the Chagas disease outbreak. We here provide recommendations to avoid further outbreaks.
Glycol methacrylate (GMA), a water and ethanol miscible plastic resin, is a medium handy to use for light microscopy embedding that has a number of advantages than paraffin embedding. The GMA ...improves the histological, morphometrical, and immunohistochemical evaluations, mainly due to the accurate assessment of cytological details. This chapter focuses on our experience in the GMA processing and describes in detail the fixation, embedding, and staining methods that we have been using for testes evaluations.
Both oxidative/nitrosative stress and alterations in DNA methylation are observed during carcinogenesis of different tumor types, but no clear correlation between these events has been demonstrated ...until now. Melanoma cell lines were previously established after submitting the nontumorigenic melanocyte lineage, melan-a, to cycles of anchorage blockade. In this work, increased intracellular oxidative species and nitric oxide levels, as well as alterations in the DNA methylation, were observed after melan-a detachment, which were also associated with a decrease in intracellular homocysteine (Hey), an element in the methionine (universal methyl donor) cycle. This alteration was accompanied by increase in glutathione (GSH) levels and methylated DNA content. Furthermore, a significant increase in dnmti and 3b expression was identified along melan-a anchorage blockade. LG-Nitro-L-arginine methyl esther (L-NAME), known as a nitric oxide synthase (NOS) inhibitor, and N-acetyl-L-cysteine (NAC) prevented the increase in global DNA methylation, as well as the increase in dnmti and 3b expression, observed during melan-a detachment. Interestingly, both L-NAME and NAC did not inhibit nitric oxide (NO) production in these cells, but abrogated superoxide anion production during anchorage blockade. In conclusion, oxidative stress observed during melanocyte anchorage blockade seems to modulate DNA methylation levels and may directly contribute to the acquisition of an anoikis-resistant phenotype through an epigenetic mechanism.
Phospholipase A2 toxins present in snake venoms interact with biological membranes and serve as structural models for the design of small peptides with anticancer, antibacterial and antiparasitic ...properties. Oligoarginine peptides are capable of increasing cell membrane permeability (cell penetrating peptides), and for this reason are interesting delivery systems for compounds of pharmacological interest. Inspired by these two families of bioactive molecules, we have synthesized two 13-mer peptides as potential antileishmanial leads gaining insights into structural features useful for the future design of more potent peptides. The peptides included p-Acl, reproducing a natural segment of a Lys49 PLA2 from Agkistrodon contortrix laticinctus snake venom, and its p-AclR7 analogue where all seven lysine residues were replaced by arginines. Both peptides were active against promastigote and amastigote forms of Leishmania (L.) amazonensis and L. (L.) infantum, while displaying low cytotoxicity for primary murine macrophages. Spectrofluorimetric studies suggest that permeabilization of the parasite's cell membrane is the probable mechanism of action of these biomolecules. Relevantly, the engineered peptide p-AclR7 was more active in both life stages of Leishmania and induced higher rates of ethidium bromide incorporation than its native template p-Acl. Taken together, the results suggest that short peptides based on phospholipase toxins are potential scaffolds for development of antileishmanial candidates. Moreover, specific amino acid substitutions, such those herein employed, may enhance the antiparasitic action of these cationic peptides, encouraging their future biomedical applications.
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•13-mer peptides based on phospholipase and oligoarginine sequences are promising leishmanicidal compounds.•Arginine may confer better antileishmanial activity to cationic peptides than lysine residues.•13-mer leishmanicidal peptides interfere with cell membrane permeabilization.•13-mer peptides showed low toxicity to mammalian cells.
Cryptococcosis is an important fungal infection in immunocompromised individuals, especially those infected with HIV. In Brazil, despite the free availability of antiretroviral therapy (ART) in the ...public health system, the mortality rate due to Cryptococcus neoformans meningitis is still high. To obtain a more detailed picture of the population genetic structure of this species in southeast Brazil, we studied 108 clinical isolates from 101 patients and 35 environmental isolates. Among the patients, 59% had a fatal outcome mainly in HIV-positive male patients. All the isolates were found to be C. neoformans var. grubii major molecular type VNI and mating type locus alpha. Twelve were identified as diploid by flow cytometry, being homozygous (AαAα) for the mating type and by PCR screening of the STE20, GPA1, and PAK1 genes. Using the ISHAM consensus multilocus sequence typing (MLST) scheme, 13 sequence types (ST) were identified, with one being newly described. ST93 was identified from 81 (75%) of the clinical isolates, while ST77 and ST93 were identified from 19 (54%) and 10 (29%) environmental isolates, respectively. The southeastern Brazilian isolates had an overwhelming clonal population structure. When compared with populations from different continents based on data extracted from the ISHAM-MLST database (mlst.mycologylab.org) they showed less genetic variability. Two main clusters within C. neoformans var. grubii VNI were identified that diverged from VNB around 0.58 to 4.8 million years ago.
The wild boar is a natural inhabitant of Europe, Asia, and North Africa and is phylogenetically the ancestor of the domestic
pig. Because of its phylogenetic and economic importance, this species is ...an interesting model for studying testis function
in boars. Therefore, the present study was performed to investigate the testis structure, spermatogenic cycle length, and
Sertoli cell (SC) and spermatogenic efficiencies in eight adult wild boars. Each spermatogenic cycle lasted 9.05 days, and
the total duration of spermatogenesis was estimated as lasting approximately 41 days. The percentages of testis volume occupied
by seminiferous tubules and by Leydig cells were 87% and 6%, respectively. The mean number of SCs per gram of testis was 42
million. The SC (round spermatids per SC) and spermatogenic (daily sperm production per gram of testis) efficiencies were
6.6 cells and 28.6 million, respectively. In general, the testis structure, overall germ cell associations at the different
stages of the seminiferous epithelium cycle, and duration of spermatogenesis in the wild boar were similar to those in domestic
pigs. Probably because of the small size of Leydig cells (400 μm 3 ), their number per gram of testis (157 million) was the highest among investigated mammalian species. Although the SC efficiency
in wild boars was low, their spermatogenic efficiency was comparable to that observed in domestic pigs, mainly because of
the higher number of SCs per gram of testis in wild boars. These data suggest that SCs became more efficient during evolution,
genetic selection, and domestication in pigs.
Abstract
The wild boar, the domestic pig ancestor, might represent a suitable model to perform comparative studies related to the testis
function in two Suidae species
Oxazine derivatives, a class of heterocyclic compounds, exhibit a variety of biological properties, such as anticonvulsant and antitumor activities. In this study, we evaluated the effect of two ...cyclohexene-fused 1,3-oxazines (cis‑1-benzyl-N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (1) and trans‑N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (2)) in cultures of Bacillus cereus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Serratia marcescens, Shigella flexneri and Staphylococcus aureus by the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC). Additionally, the ex vivo antiparasitic activity of oxazines was assessed against Schistosoma mansoni, a helminth that is one of the major agents of the disease schistosomiasis Also, oxazines were evaluated on three tumor cell lines, NCI-H292 (human lung carcinoma), MCF-7 (human breast adenocarcinoma) and HEp-2 (human cervix carcinoma), and two normal cell lines (Vero and red blood cells). Bioassays revealed that oxazine 2 is more effective against bacteria than oxazine 1, with the lowest MIC and MBC values of 3.91 and 32.5μg/mL, respectively. Similarly, compound 2 demonstrated higher antiparasitic activity than 1, and scanning electron microscopy analysis showed several morphological alterations in the tegument of worms in a concentration-dependent manner. In contrast, both oxazines exhibited low cytotoxic effects on cancer and normal cell lines. These results indicated that oxazines exerted direct effects on bacteria and parasite schistosomes. More importantly, since schistosomiasis control programs rely on one drug, praziquantel, oxazines may have the potential to become new antischistosomal agents.
•Oxazine 2 exhibited antischistosomal activity against Schistosoma mansoni•Oxazine 2 displayed activity against Staphylococcus aureus and Escherichia coli•Oxazine 2 caused death and tegumental damage of adult S. mansoni worms•Oxazines exhibited low cytotoxic effects on human cancer cell lines.
In this study, the authors report morphological deformities in driftwood catfish Trachelyopterus galeatus (Auchenipteridae), an invasive catfish occurring in the Upper Paraná River basin, Brazil. The ...frequency of anomalous individuals reached 18.3% of all catches. X‐ray images showed anomalies, or total absence of structures, in the pelvic girdle. The authors also observed the absence of the adipose fin and mental barbels. These findings are of extreme importance for evidencing the anthropogenic impact on aquatic communities as the region suffers within fragmentation by dams and pollution from several human activities. This sort of information can be used in management systems and environmental monitoring, especially to protect other species and the native fish assemblage.
Several studies have investigated the antinociceptive, immunomodulatory and anti-inflammatory properties of compounds found in the lavender essential oil (LEO), however to date, there is still lack ...of substantial data. The objective of this study was to assess the antioxidant, anti-inflammatory and antinociceptive effects of lavender essential oil. The 1,1-diphenyl-2-picrylhydrazyl radical decolorization assay was used for antioxidant activity evaluation. The anti-inflammatory activity was tested using two models of acute inflammation: carrageenan-induced pleurisy and croton oil-induced ear edema. The antinociceptive activity was tested using the pain model induced by formalin. LEO has antioxidant activity, which is dose-dependent response. The inflammatory response evoked by carrageenan and by croton oil was reduced through the pre-treatment of animals with LEO. In the pleurisy model, the drug used as positive control, dexamethasone, was more efficacious. However, in the ear swelling, the antiedematogenic effect of the oil was similar to that observed for dexamethasone. In the formalin test, LEO consistently inhibited spontaneous nociception and presented a similar effect to that of tramadol. The results of this study reveal (in vivo) the analgesic and anti-inflammatory activities of LEO and demonstrates its important therapeutic potential.
MicroRNAs perform important roles in the post-transcriptional regulation of gene expression. Sequencing as well as functional studies using antisense oligonucleotides indicate important roles for ...microRNAs during the development of epilepsy through targeting transcripts involved in neuronal structure, gliosis and inflammation. MicroRNA-22 (miR-22) has been reported to protect against the development of epileptogenic brain networks through suppression of neuroinflammatory signalling. Here, we used mice with a genetic deletion of miR-22 to extend these insights. Mice lacking miR-22 displayed normal behaviour and brain structure and developed similar status epilepticus after intraamygdala kainic acid compared to wildtype animals. Continuous EEG monitoring after status epilepticus revealed, however, an accelerated and exacerbated epilepsy phenotype whereby spontaneous seizures began sooner, occurred more frequently and were of longer duration in miR-22-deficient mice. RNA sequencing analysis of the hippocampus during the period of epileptogenesis revealed a specific suppression of inflammatory signalling in the hippocampus of miR-22-deficient mice. Taken together, these findings indicate a role for miR-22 in establishing early inflammatory responses to status epilepticus. Inflammatory signalling may serve anti-epileptogenic functions and cautions the timing of anti-inflammatory interventions for the treatment of status epilepticus.
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