Interactions between lipid source and vitamin A on broiler performance, blood parameters, fat and protein deposition rate, and bone development.

A total of 2622 male broilers were distributed in a 2 × 5 factorial design, using 2 lipid sources (soybean oil and palm fat), 5 levels of vitamin A supplementation (0, 3,000, 6,000, 12,000, and 24,000 IU kg-1), with 10 replicates, and also 1 control diet (CD) for each lipid source used (7 replicates), each experimental unit being composed of 23 birds. During the first 21 d (how were the birds fed) and from 22 to 42 d of age, a redistribution of the treatments was carried out in a 2 × 2 × 5 factorial design: half of the repetitions of each treatment received the diet of the initial treatment, and the others received the CD with its type of lipid source. In the phase from 1 to 21 d of age, the effect of lipid source on feed intake (FI) and feed conversion ratio (FCR), and the effect of vitamin supplementation on FI and weight gain (WG) were observed, with a quadratic response for both variables. At 42 d of age, the lipid source and vitamin A level influenced the FI, whereas the WG and FCR showed interactions between period and the level of vitamin A supplementation. Neither lipid source resulted in blood parameters out of the typical pattern for birds, and the same was observed in relation to dietary vitamin A supplementation. From 1 to 21 d of age, a vitamin A supplementation of 15,585 IU kg-1 was estimated, and at 42 d, 15,527 IU kg-1 and 15,148 IU kg -1 were estimated for the periods 1 to 21 d and 1 to 42 d, respectively.

Metabolic inhibitors accentuate the anti-tumoral effect of HDAC5 inhibition.

The US FDA approval of broad-spectrum histone deacetylase (HDAC) inhibitors has firmly laid the cancer community to explore HDAC inhibition as a therapeutic approach for cancer treatment. Hitting one HDAC member could yield clinical benefit but this required a complete understanding of the functions of the different HDAC members. Here we explored the consequences of specific HDAC5 inhibition in cancer cells. We demonstrated that HDAC5 inhibition induces an iron-dependent reactive oxygen species (ROS) production, ultimately leading to apoptotic cell death as well as mechanisms of mitochondria quality control (mitophagy and mitobiogenesis). Interestingly, adaptation of HDAC5-depleted cells to oxidative stress passes through reprogramming of metabolic pathways towards glucose and glutamine. Therefore, interference with both glucose and glutamine supply in HDAC5-inhibited cancer cells significantly increases apoptotic cell death and reduces tumour growth in vivo; providing insight into a valuable clinical strategy combining the selective inhibition of HDAC5 with various inhibitors of metabolism as a new therapy to kill cancer cells.

Exigência de lisina digestível para poedeiras semipesadas de 50 a 66 semanas de idade / Digestible lysine requirement for laying hens from 50 to 66 weeks of age

Com o objetivo de determinar a exigência de lisina digestível para poedeiras semipesadas no período de 50 a 66 semanas de idade, foi realizado experimento utilizando-se 150 poedeiras Shaver Brown, distribuídas em delineamento inteiramente ao acaso, com cinco tratamentos (níveis de lisina digestível: 0,79; 0,82; 0,85; 0,88 e 0,91%), seis repetições e cinco aves por unidade experimental. Foram avaliados a produção de ovos, peso médio e a massa de ovos, consumo de ração e de lisina, conversão alimentar por massa e por dúzia de ovos, gravidade específica, unidade Haugh, o índice de gema e albúmen, porcentagem de albúmen, gema e casca. O consumo de ração, a conversão alimentar por massa e dúzia de ovos, a produção, o peso e a massa de ovos não foram influenciados (P>0,05) pelos níveis de lisina digestível. Houve aumento linear no consumo de lisina (P<0,01) com o incremento dos níveis desse aminoácido nas rações. As porcentagens de albúmen, gema e casca não foram influenciadas (P>0,05) pelos níveis de lisina digestível estudados. Os níveis de lisina influenciaram de forma quadrática (P>0,05) a unidade Haugh e o índice de albúmen, sendo estimados os níveis de 0,884 e 0,868% de lisina digestível, respectivamente. Para o índice de gema, a associação do modelo quadrático ao Linear Response Plateau (LRP) estimou o nível de 0,903% de lisina digestível. Quando o objetivo é maximizar a qualidade interna dos ovos, recomenda-se o nível dietético de 0,884%, 0,868% e 0,903% de lisina digestível para unidade Haugh, índice de albúmen e índice de gema, respectivamente.

With the objective of determining the requirement of digestible lysine for brown-egg laying hens in the period from 50 to 66 weeks of age, an experiment was carried out using 150 Shaver Brown laying hens, distributed in a completely randomized design, with five treatments (digestible lysine levels: 0.79, 0.82, 0.85, 0.88 and 0.91%), six replications and five birds per experimental unit. The production of eggs, weight and the egg mass, feed intake and lysine, feed mass and dozen eggs, specific gravity, Haugh unit, yolk and albumen index, percentage of albumen, yolk and bark were analyzed. Feed intake, feed conversion per dozen of eggs s and per egg mass, egg production, egg weight and egg mass were not influenced (P>0.05) by digestible lysine levels. There was a linear increase in lysine intake (P<0.01) with increasing levels of this amino acid in the diets. The albumen, yolk and shell percentages were not influenced (P>0.05) by studied digestible lysine levels. Lysine levels had a quadratic effect (P>0.05) Haugh unit and albumen index being estimated as 0.884 and 0.868% digestible lysine levels, respectively. For yolk index, the association of the quadratic model to Linear Response Plateau (LRP) estimated the level of 0.903% digestible lysine. When the aim is to maximize the internal egg quality, a dietary level of 0.884%, 0.868% and 0.903% digestible lysine for Haugh unit, albumen index and yolk index, respectively is recommended.

Pharmacological blockage and P2X7 deletion hinder aversive memories: reversion in an enriched environment.

Adenosine triphosphate (ATP) plays a role in cell signaling. It was soon proposed that ATP activates ionotropic P2X receptors, exerting an influence on neurons as well as on glial cells. In addition to the fact that the activation of P2X and P2Y receptors can stimulate or inhibit the release of glutamate from rat hippocampal neurons, the release of ATP has been implicated in hippocampal long-term potentiation (LTP). Through different behavioral paradigms, this study aimed to investigate the participation of P2X7R in genetically modified (knockout (KO)) mice with the suppressed expression of this receptor and in the pharmacological blockage of this receptor in rats, as well as to evaluate the effect of environmental enrichment on potential mnemonic deficits. The results suggest that P2X7R participates in aversive memory processes: pharmacological blockage with the selective P2X7R antagonist, A-740003, in different time frames elicited dose-dependent impairments in memory acquisition, consolidation and retrieval in rats that were submitted to the contextual fear-conditioning (FC) task, and the deletion of P2X7R hampered the aversive memory processes of mice that were subjected to the FC paradigm. Experiments using mice that were subjected to environmental enrichment suggest that this form of stimulation reverses mnemonic impairments that are ascribed to the absence of the P2X7R, suggesting that these receptors do not participate on such a reversal. Finally, no alterations were observed in the habituation memory of P2X7KO mice.

Quantidade de metionina+cistina digestível para poedeiras semipesadas de 75 a 91 semanas de idade / Nutritional requirement of digestible methionine + cystine for brown-egg laying hens from 75 to 91weeks of age

Determinaram-se as exigências nutricionais de metionina+cistina digestível para poedeiras de linhagem comercial no segundo ciclo de produção de 75 a 91 semanas de idade, utilizando-se 150 aves semipesadas em delineamento inteiramente ao acaso. Estas foram distribuídas em cinco tratamentos, seis repetições e cinco aves por unidade experimental, alimentadas com uma dieta basal contendo 2.859kcal/kg de energia metabolizável e 16,30% de proteína bruta, suplementada com 0,132; 0,173; 0,215; 0,256 e 0,298% de DL-metionina (98%), de forma a proporcionar 0,588; 0,628; 0,669; 0,709 e 0,750% de metionina+cistina digestível na dieta. A inclusão de metionina+cistina obedeceu, respectivamente, às proporções de 67, 72, 77, 81 e 86% com a lisina fixada em 0,872%. Avaliaram-se os consumos de ração e de metionina+cistina, a conversão alimentar por dúzia e por massa de ovos, a taxa de postura, o peso e a massa de ovos, a porcentagem dos componentes dos ovos e a qualidade interna dos ovos e o ganho de peso. A inclusão de metionina+cistina digestível nas quantidades indicadas não exerceu efeito (P>0,05) sobre as características de produção e qualidade interna e externa dos ovos. A exigência estimada foi de 0,588% de metionina+cistina digestível, correspondendo ao consumo de 654,73mg/ave/dia.

This work determined the nutritional requirements for methionine + cystine for commercial hens in the second production cycle from 75 to 91 weeks of age, using 150 brown-egg layer hens in a completely randomized design, distributed in five treatments, six replicates of five hens each and fed a basal diet containing 2859kcal/kg of metobolizable energy, 16.30% crude protein supplemented with 0.132, 0.173, 0.215, 0.256 and 0.298% DL-methionine (98%), in order to provide 0.588, 0.628, 0.669, 0.709 and 0.750% methionine + cystine in the diet. The inclusion of methionine + cystine followed, respectively, the proportions of 67, 72, 77, 81 and 86% with lysine fixed at 0.872%. The feed intake, methionine + cystine intake, feed conversion per dozen eggs and egg mass, percentage of the eggs, egg weight, egg mass, percentage of egg components and internal quality of eggs and weight gain were evaluated. The inclusion methionine + cystine in the amounts indicated had no effect (P> 0.05) on the production characteristics and internal and external quality of eggs. The requirement was estimated at 0.588% methionine + cystine intake corresponding to 654.73mg/hen/day.

HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells.

Histone deacetylases (HDACs) form a family of enzymes, which have fundamental roles in the epigenetic regulation of gene expression and contribute to the growth, differentiation, and apoptosis of cancer cells. In this study, we further investigated the biological function of HDAC5 in cancer cells. We found HDAC5 is associated with actively replicating pericentric heterochromatin during late S phase. We demonstrated that specific depletion of HDAC5 by RNA interference resulted in profound changes in the heterochromatin structure and slowed down ongoing replication forks. This defect in heterochromatin maintenance and assembly are sensed by DNA damage checkpoint pathways, which triggered cancer cells to autophagy and apoptosis, and arrested their growth both in vitro and in vivo. Finally, we also demonstrated that HDAC5 depletion led to enhanced sensitivity of DNA to DNA-damaging agents, suggesting that heterochromatin de-condensation induced by histone HDAC5 silencing may enhance the efficacy of cytotoxic agents that act by targeting DNA in vitro. Together, these results highlighted for the first time an unrecognized link between HDAC5 and the maintenance/assembly of heterochromatin structure, and demonstrated that its specific inhibition might contribute to increase the efficacy of DNA alteration-based cancer therapies in clinic.

Urinary neopterin and kynurenine in patients submitted to surgical stress with different inhalational anesthetics (halothane or isoflurane).

Measurements were taken of urinary levels of neopterin (NPT) and kynurenine (KYN), using an HPLC method for their simultaneous analysis in patients submitted to anesthetical surgical stress with two different inhalational anesthetics (halothane and isoflurane). We studied twenty-one women affected by uterine fibromyomatosis and submitted to total hysterectomy (mean age of 42.7+/-5.4 years). They showed the same pre-operative evaluation (ASA-1), and underwent the same i.v. anesthetic treatment. Our patients were randomized in two groups: Group A: 11 patients had halothane as an inhalational anesthetic drug for the maintenance of the anesthetic induction (mean time= 1 h). Group B: 10 patients had isoflurane. A significant decrease in urinary NPT and KYN, parallel to serum-NPT, was found 4 h after anesthetic induction. Raised NPT levels appeared 24 h after A.I. with significant increased levels after 7 days. A strong correlation between urinary and serum NPT levels was seen (Rs= 0.74; p < 0.001). Significantly low KYN levels were observed both 4 h and 24 h after A.I.. In addition to the delayed increase of the excretory KYN levels, significantly raised KYN levels in Group B (isoflurane) 48 h after A.I. (10.59+/-14.31 vs 5.99+/-7.17 micromol/mol creat.; p < 0.01) were shown, whereas in Group A (halothane) we observed a progressive increase as compared to the pre-surgery values starting from 72 h after surgery. Our data seem to show that: (a) it is possible to have a biochemical and non invasive monitoring of the anesthetical-surgical stress on MM "priming" activity; (b) the activation of the phagocyte compartment is one of the earlier immunological events after surgery (NPT), but the efficiency of this "priming" appears to be delayed (KYN); (c) isoflurane appears to induce an earlier recovery in MM activation.