Methane emission, milk yield and behavior of ewes kept on pastures or supplemented with concentrate based on corn grain or whole cottonseed

ABSTRACT This study aimed to evaluate methane emission, milk yield and behavior of ewes kept exclusively on irrigated pasture of Tifton 85 grass (Cynodon spp.) or supplemented with ground corn or whole cottonseed (WCS) based concentrates. Twelve Lacaune x Santa Ines ewes (43.07±0.83 kg of body weight, 77±24 days after parturition, on average) were distributed in replicated 3x3 Latin square. Treatments consisted of three diets: pasture (no concentrate supplementation); corn (pasture + corn-based supplement); whole cottonseed (pasture + whole cottonseed-based supplement), offering 0.5 kg/ewe/day. The WCS group showed the highest concentrate dry matter intake (DMI) (p=0.049) and crude protein (CP) intake (p=0.001) compared to the others. There was no difference on total DMI (p=0.115) for the tested diets. Animals exclusively kept on pasture had the greatest forage DMI (p=0.004), lowest CP digestibility (p=0.015), showed longer grazing time (p=0.01) and shorter idle time (p=0.01) compared to the supplemented groups. Milk yield (0.36 kg/ewe/day) (p=0.15) and methane emission (33.12 g/ewe/day) (p=0.95) were similar for all three evaluated groups. Supplementation with concentrate based on corn or whole cottonseed does not improve productive performance nor decrease methane emission. However, lactating ewes kept exclusively in pasture show longer grazing time, without changes in milk yield and methane emission

Enantiomers of nifurtimox do not exhibit stereoselective anti-Trypanosoma cruzi activity, toxicity, or pharmacokinetic properties

With the aim of improving the available drugs for the treatment of Chagas disease, individual enantiomers of nifurtimox were characterized. The results indicate that the enantiomers are equivalent in their in vitro activity against a panel of Trypanosoma cruzi strains; in vivo efficacy in a murine model of Chagas disease; in vitro toxicity and absorption, distribution, metabolism, and excretion characteristics; and in vivo pharmacokinetic properties. There is unlikely to be any therapeutic benefit of an individual nifurtimox enantiomer over the racemic mixture

Pharmacological inhibition of lysine-specific demethylase 1 (LSD1) induces global transcriptional deregulation and ultrastructural alterations that impair viability in Schistosoma mansoni

Treatment and control of schistosomiasis still rely on only one effective drug, praziquantel (PZQ) and, due to mass treatment, the increasing risk of selecting for schistosome strains that are resistant to PZQ has alerted investigators to the urgent need to develop novel therapeutic strategies. The histone-modifying enzymes (HMEs) represent promising targets for the development of epigenetic drugs against Schistosoma mansoni. In the present study, we targeted the S. mansoni lysine-specific demethylase 1 (SmLSD1), a transcriptional corepressor, using a novel and selective synthetic inhibitor, MC3935, which was used to treat schistosomula and adult worms in vitro. By using cell viability assays and optical and electron microscopy, we showed that treatment with MC3935 affected parasite motility, egg-laying, tegument, and cellular organelle structures, culminating in the death of schistosomula and adult worms. In silico molecular modeling and docking analysis suggested that MC3935 binds to the catalytic pocket of SmLSD1. Western blot analysis revealed that MC3935 inhibited SmLSD1 demethylation activity of H3K4me1/2. Knockdown of SmLSD1 by RNAi recapitulated MC3935 phenotypes in adult worms. RNA-Seq analysis of MC3935-treated parasites revealed significant differences in gene expression related to critical biological processes. Collectively, our findings show that SmLSD1 is a promising drug target for the treatment of schistosomiasis and strongly support the further development and in vivo testing of selective schistosome LSD1 inhibitors