Dogs naturally infected with Leishmania Infantum (=L. chagasi) were treated with miltefosine using different therapeutic regimens. The animals were evaluated for clinical evolution, biochemical parameters, parasite load (by real-time PCR), cytokine levels and humoral response. After treatment and during the following 24 months, there was progressive clinical improvement and complete recovery in 50% (7/14) of the treated animals. There was a decrease in the smear positivity of the bone marrow after treatment, and there was also a gradual and constant decrease in positive cultures at the end of the follow-up period. However, the PCR detection of parasite DNA remained positive. In general, all animals presented a significant increase in parasite load 6 months after treatment. The IFN-γ levels in all the groups tended to increase during follow-up period, regardless of the miltefosine dose administered. The IL-4 and IL-10 levels of the animals tended to decrease during follow-up, except after 300 days when only IL-10 increased. The serum antibodies identified antigens that ranged from 116 kDa to less than 29 kDa in the Western blot assay. Furthermore, 300 days after treatment, qualitative and quantitative differences in the antigen profiles were observed. Antigens of 97 and 46 kDa were the most intensely recognized. Higher levels of antigen-specific Leishmania IgG were detected before and 300 days after treatment in all groups. Taking together, the improvement in the clinical symptoms was not followed by parasitological clearance, suggesting that treatment with miltefosine is not recommended, especially in endemic areas like Brazil, where children are the major victims and dogs are involved in the maintenance of the parasite cycle.

The potential genotoxic effects of engineered nanomaterials (ENMs) may occur through the induction of DNA damage or the disruption of DNA repair processes. Inefficient DNA repair may lead to the accumulation of DNA lesions and has been linked to various diseases, including cancer. Most studies so far have focused on understanding the nanogenotoxicity of ENM-induced damages to DNA, whereas the effects on DNA repair have been widely overlooked. The recently developed fluorescence multiplex–host-cell reactivation (FM-HCR) assay allows for the direct quantification of multiple DNA repair pathways in living cells and offers a great opportunity to address this methodological gap. Herein an FM-HCR-based method is developed to screen the impact of ENMs on six major DNA repair pathways using suspended or adherent cells. The sensitivity and efficiency of this DNA repair screening method were demonstrated in case studies using primary human small airway epithelial cells and TK6 cells exposed to various model ENMs (CuO, ZnO, and Ga2O3) at subcytotoxic doses. It was shown that ENMs may inhibit nucleotide-excision repair, base-excision repair, and the repair of oxidative damage by DNA glycosylases in TK6 cells, even in the absence of significant genomic DNA damage. It is of note that the DNA repair capacity was increased by some ENMs, whereas it was suppressed by others. Overall, this method can be part of a multitier, in vitro hazard assessment of ENMs as a functional, high-throughput platform that provides insights into the interplay of the properties of ENMs, the DNA repair efficiency, and the genomic stability.

No abstract

Improvements in sow productivity have raised questions regarding dietary vitamin D recommendations. The present study aimed to evaluate the effects of the housing system with access to sunlight exposure and supplementation of 25‐hydroxicholecalciferol on performance and serum levels of 25(OH)D3 in sows during gestation and lactation. Sows were distributed in an experimental design with two housing systems: gestation crates or gestation free‐range system with external area for sunlight exposure; and two diets: 0 or 50 μg of 25‐hydroxicholecalciferol kg−1. The use of 25‐hydroxicholecalciferol tended (P = 0.052) to improve total born and influenced (P = 0.046) on number of born alive. Litter weight at birth was also increased (P = 0.01) by 25‐hydroxicholecalciferol supplementation; 25‐hydroxicholecalciferol supplementation and housing system (free‐range with sunlight exposure) tended to increase weaning weight (P = 0.07) and litter daily gain (P = 0.051) during lactation. Exposure to sunlight and 25‐hydroxicholecalciferol supplementation increased 25(OH)D3 serum levels when compared with control treatment during gestation (136.95 vs. 113.92 ng mL−1; P = 0.035) and lactation (120.29 vs. 88.93 ng mL−1; P = 0.026). In conclusion, the association of 25‐hydroxicholecalciferol supplementation with exposure to sunlight during gestation improved significantly 25(OH)D3 serum levels and consequently performance traits in gestation and lactation.

No abstract

Vitamin D is an essential key modulator of metabolism in pigs. Improvements in sow productivity have raised questions regarding dietary vitamin recommendations. In this sense, vitamin D serum levels could be limiting to attend high demanding phases. The present study aimed to study the impact of housing system with access to sunlight exposure and supplementation of 25(OH)D3 (Hy-D®) on performance and serum levels of 25(OH)D3 in sows during gestation and lactation. A total of 48 mixed parity sows were distributed in a factorial 2 x 2 experimental design (2 housing systems: gestation crates or free-range system with external area for sunlight exposure; and 2 diets: 0 or 50µg of Hy-D® per kg of diet). Sows remained in treatments from insemination until weaning. The housing systems did not influence (P >0.10) performance traits during gestation nor lactation. The use of Hy-D® tended (P=0.052) to improve total born (17.5 vs. 15.4, respectively 50 and 0 µg Hy-D®) and influenced (P=0.046) on number of born alive (13.4 vs. 12.2, respectively 50 and 0 µg Hy-D®). Litter weight at birth was influenced (P=0.01) by Hy-D® supplementation (20.8 vs. 17.5 kg, respectively 50 and 0 µg Hy-D®). Hy-D® supplementation and housing system (free-range with sunlight exposure) tended to increase weaning weight (P=0.07) and litter daily gain (P=0.051) during lactation. Exposure to sunlight and Hy-D® influenced (P=0.008) 25(OH)D3 serum levels when compared to control (without sunlight and 0 µg of Hy-D®) during gestation (132.3 vs. 116.6 ng mL-1, respectively) and lactation (120.3 vs. 92.2 ng mL-1, respectively). In conclusion, our findings showed that the supplementation of Hy-D® during gestation and lactation has a significant impact on performance of sows and their litters. Also, the association of Hy-D® supplementation with exposure to sunlight during gestation improved significantly 25(OH)D3 serum levels and consequently performance traits in gestation and lactation.

Background: Obesity is one of the main health problems in the world today and dysbiosis seem to be one of the factors involved. The aim of this study was to examine the impact of synbiotic supplementation in obesity and microbiota in ob/ob mice. 20 animals were divided into four groups: Obese Treated (OT) and Control (OC), Lean Treated (LT) and Control (LC). All animals received standard diet for 8 weeks. Treated groups received a synbiotic in water while nontreated groups received water. After 8 weeks, all animals were sacrificed and gut tissue mRNA isolation and stool samples by microbiota analysis were collected. Beta-catenin, occludin, cadherin and zonulin were analyzed in gut tissue by RT-qPCR. Microbiome DNA was extracted from stool samples and sequenced using the Ion PGM Torrent platform. Results: The synbiotic supplementation reduced body weight gain in OT group comparing with OC (p=0.0398), increase of Enterobacteriaceae (p=0.005) and decrease of Cyanobacteria (p=0.047), Clostridiaceae (p=0.026), Turicibacterales (p=0.005) and Coprococcus (p=0.047). In the other hand, a significant reduction of Sutterella bacteria (p=0.009) and Turicibacter (p=0.005) was observed in LT group compared to LC. Alpha and beta diversities were differ between all treated groups. Beta-catenin gene expression was significantly decreased in the gut tissue of OT group (p≤0.0001) when compared to other groups. No changes were observed in occludin, cadherin and zonulin gene expression in the gut tissue. Conclusion: The synbiotics supplementation prevents excessive weight gain, modulates the gut microbiota, and reduces beta-catenin expression in ob/ob mice.

Exossomos derivados de rASCs contêm miRNAs envolvidos na regeneração cardíaca ..