Effect of amino acid blend as alternative to antibiotics for growing pigs.

This study aimed to evaluate the effect of supplementing arginine (Arg) + glutamine (Gln) replacing antibiotics on performance, immune response, and antioxidant capacity of pigs in the growing phase. One hundred fifty 63-d-old pigs with initial body weight (BW) of 25.0 ± 1.46 kg were distributed in a randomized block design, with three treatments and ten replicates. The three diets were control; antibiotic, control + 100 mg/kg tiamulin and 506 mg/kg oxytetracycline; amino acid, control + 10 g/kg Arg and 2 g/kg Gln. Dietary treatments were fed from 63 to 77 d. Following the treatment period, all pigs were fed the control diet from 77 to 90 d. Data were analyzed using GLIMMIX and UNIVARIATE in SAS 9.4. From 63 to 70 d, pigs fed diets with antibiotics had improved (P < 0.05) average daily feed intake, average daily weight gain (ADG), gain to feed ratio (G:F), and 70-d BW compared to those fed control or amino acid diets. From 70 to 77 d, including antibiotics in the diet increased (P < 0.05) ADG and 77-d BW. From 77 to 90 d, pigs fed control or amino acid diets had greater (P < 0.05) ADG than those fed an antibiotic diet. From 63 to 90 d, although pig performance was not affected (P > 0.05), growth curve of pigs fed the antibiotic diets was different (P < 0.05) from those fed the control and amino acids diets. At 70 d, serum tumor necrosis factor-α and diamine oxidase (DAO) were lower (P < 0.05) in pigs fed the antibiotic diet than the control diet, and pigs fed the amino acid diet had intermediate results. Ferric reducing antioxidant power (FRAP) was lower (P < 0.05) in pigs fed the amino acid diet than the antibiotic diet, and pigs fed the control diet had intermediate results. Serum immunoglobulin A was lower (P < 0.05) in pigs fed the antibiotic diet. At 77 d, DAO and serum immunoglobulin G were lower (P < 0.05) in pigs fed the antibiotic diet. FRAP was lower (P < 0.05) in pigs fed the amino acid and control diets. Serum malondialdehyde was higher (P < 0.05) in pigs fed the amino acid diet than those fed the control diet, and pigs fed the antibiotic diet had intermediate results. At 90 d, antibiotics or amino acids did not affect (P > 0.05) serum parameters. Amino acid blend supplementation at the selected doses in this study did not positively affect growing pigs. Although from 63 to 77 d, antibiotics improved performance, when considering the overall study period, growing pigs did not benefit from a diet containing antibiotics.

Dietary antibiotics have been used in pig farming practices to avoid health problems, improving animal growth performance. However, antimicrobial resistance due to the use of antibiotics in farms is considered to be a global health challenge. Arginine and glutamine are amino acids with potential to improve gut health, immune function, and growth performance. Thus, the study aimed to evaluate the supplementation of those amino acids as an alternative to the use of dietary antibiotic for pigs. Moreover, after a 14-d treatment phase, we still monitor the pigs to evaluate the carryover effects of the antibiotics and amino acids. Amino acid supplementation at the selected doses in this study did not positively affect pigs. Although during the treatment phase, antibiotics improved performance, when considering the overall study period, pigs did not benefit from a diet containing antibiotics. Thus, antibiotics caused transient alterations in pig performance and should be further investigated, potentially guiding future research on its use and alternative technologies.

The Effects of Angiotensin II or Angiotensin 1-7 on Rat Pial Microcirculation during Hypoperfusion and Reperfusion Injury: Role of Redox Stress.

Renin-angiotensin systems produce angiotensin II (Ang II) and angiotensin 1-7 (Ang 1-7), which are able to induce opposite effects on circulation. This study in vivo assessed the effects induced by Ang II or Ang 1-7 on rat pial microcirculation during hypoperfusion-reperfusion, clarifying the mechanisms causing the imbalance between Ang II and Ang 1-7. The fluorescence microscopy was used to quantify the microvascular parameters. Hypoperfusion and reperfusion caused vasoconstriction, disruption of blood-brain barrier, reduction of capillary perfusion and an increase in reactive oxygen species production. Rats treated with Ang II showed exacerbated microvascular damage with stronger vasoconstriction compared to hypoperfused rats, a further increase in leakage, higher decrease in capillary perfusion and marker oxidative stress. Candesartan cilexetil (specific Ang II type 1 receptor (AT1R) antagonist) administration prior to Ang II prevented the effects induced by Ang II, blunting the hypoperfusion-reperfusion injury. Ang 1-7 or ACE2 activator administration, preserved the pial microcirculation from hypoperfusion-reperfusion damage. These effects of Ang 1-7 were blunted by a Mas (Mas oncogene-encoded protein) receptor antagonist, while Ang II type 2 receptor antagonists did not affect Ang 1-7-induced changes. In conclusion, Ang II and Ang 1-7 triggered different mechanisms through AT1R or MAS receptors able to affect cerebral microvascular injury.

Effects of grain processing methods on the expression of genes involved in volatile fatty acid transport and pH regulation, and keratinization in rumen epithelium of beef cattle.

Two experiments were carried out to evaluate the effects of corn and sorghum with different processing methods on the expression of genes involved in volatile fatty acids transport and pH regulation, and ruminal keratinization in rumen epithelium of finishing bulls. For Exp. 1, five rumen cannulated Nellore bulls were used in a 5x5 Latin square arrangement, with 14 d for adaptation and 9 d for sample collection. Treatments were: dry ground corn, dry ground sorghum, reconstituted corn, reconstituted sorghum, and control (forage-based diet). Samples of rumen epithelium from ventral sac were excised, rinsed, snap-frozen and stored at -80°C until total RNA isolation and quantitative real-time PCR analysis. In the Exp. 2, 24 Nellore bulls were assigned to a completely randomized design lasting 168 d. Experimental treatments were similar to those at Exp. 1, but without the control treatment. After the experimental period, bulls were slaughtered and rumen epithelium samples were rapidly excised for further histological analysis. Rumen epithelial tissue from animals fed reconstituted corn had lower expression of downregulated-in-adenoma (P = 0.03) and Na+/H+ exchanger 2 (trend; P = 0.09). The expression of Na+/ H+ exchanger 1 (P = 0.10) and putative anion transporter (P = 0.06) tended to be lower in rumen epithelium of bulls fed reconstituted grains. Ruminal concentration of valerate was greater for animals fed reconstituted grain (P = 0.01). Likewise, animals fed reconstituted corn tended to have greater butyrate ruminal concentration (P = 0.08). Keratinized layer thickness did not differ among treatments (P > 0.10). Therefore, reconstituted grains (especially corn) decrease the mRNA expression of genes involved in volatile fatty acids transport and pH control in the rumen epithelium.

Lisina digestível para leitoas em fase de crescimento / Digestible lysine for growing gilts

Oitenta leitoas (24,2±1,52kg) com alto potencial genético para deposição de carne na carcaça foram distribuídas em experimento de blocos ao acaso para avaliar cinco níveis de lisina digestível (Ld) (9, 10, 11, 12 e 13g kg-1) durante a fase de crescimento (63 a 103 dias de idade). Os animais foram alojados em pares e alimentados à vontade. No início e ao final do período experimental, as leitoas foram pesadas e submetidas à análise de ultrassom para avaliação da área de olho de lombo (AOL) e espessura de toucinho (ET). Os níveis de Ld proporcionaram aumento linear (P<0,05) do ganho de peso diário (GPD) e, apesar dessa variação, não houve aumento no valor absoluto do GPD a partir do nível de 12g kg-1 de Ld. A conversão alimentar (CA) reduziu (P<0,01) de forma quadrática até o nível estimado de 11,9g kg-1 de Ld. A AOL das leitoas aumentou (P<0,05) de forma linear. No entanto, o modelo "Linear Response Plateau" foi o que melhor se ajustou aos dados, estimando em 12,5g kg-1 o nível a partir do qual ocorreu platô. Não foi verificada influência (P>0,05) dos níveis de Ld sobre o consumo de ração diário (CRD) e ET. Os níveis de 12,0 e 12,5g kg-1 de Ld na dieta, correspondentes, respectivamente, ao consumo de lisina digestível diário (CLdD), de 23,6 e 24,6g, proporcionam os melhores resultados de desempenho e área de olho de lombo de leitoas em fase de crescimento (63 aos 103 dias de idade).

Eighty gilts (24.2±1.52kg) with high genetic potential for lean gain were used in a randomized complete block design to evaluate five digestible lysine levels (9, 10, 11, 12 and 13g kg-1) during the growing phase (63 to 103 days of age). Gilts were housed in pair and fed their respective diets ad libitum. At the begging and the ending of the experimental period, gilts were weighed and scanned by ultrasound to measure loin area, as well as fat depth. The digestible lysine levels linearly increase (P<0.05) average daily gain and loin area of gilts in growing phase. However, there was no difference for average daily gain at levels above 12g kg-1 while the "Linear Response Plateau" model was that better fitted to the loin area data that stabilized in a plateau starting from the level of 12.5g kg-1. The feed:gain ratio was improved (P<0.01) quadratically until the estimated level of 11.9g kg-1 of digestible lysine. There was no effects (P>0.05) of the treatments on the fat depth and feed intake. The digestible lysine levels of 12 and 12.5g kg-1, corresponding to the intake of 23.6 e 24.6g dia-1, provide the best results of performance and loin area of growing gilts (63 to 103 days old).

Identification and characterization of alternative exon usage linked glioblastoma multiforme survival.

BACKGROUND: Alternative exon usage (AEU) is an important component of gene regulation. Exon expression platforms allow the detection of associations between AEU and phenotypes such as cancer. Numerous studies have identified associations between gene expression and the brain cancer glioblastoma multiforme (GBM). The few consistent gene expression biomarkers of GBM that have been reported may be due to the limited consideration of AEU and the analytical approaches used. The objectives of this study were to develop a model that accounts for the variations in expression present between the exons within a gene and to identify AEU biomarkers of GBM survival. METHODS: The expression of exons corresponding to 25,403 genes was related to the survival of 250 individuals diagnosed with GBM in a training data set. Genes exhibiting AEU in the training data set were confirmed in an independent validation data set of 78 patients. A hierarchical mixed model that allows the consideration of covariation between exons within a gene and of the effect of the epidemiological characteristics of the patients was developed to identify associations between exon expression and patient survival. This general model describes all three possible scenarios: multi-exon genes with and without AEU, and single-exon genes. RESULTS: AEU associated with GBM survival was identified on 2477 genes (P-value < 5.0E-04 or FDR-adjusted P-value < 0.05). G-protein coupled receptor 98 (Gpr98) and epidermal growth factor (Egf) were among the genes exhibiting AEU with 30 and 9 exons associated with GBM survival, respectively. Pathways enriched among the AEU genes included focal adhesion, ECM-receptor interaction, ABC transporters and pathways in cancer. In addition, 24 multi-exon genes without AEU and 8 single-exon genes were associated with GBM survival (FDR-adjusted P-value < 0.05). CONCLUSIONS: The inferred patterns of AEU were consistent with in silico AS models. The hierarchical model used offered a flexible and simple way to interpret and identify associations between survival that accommodates multi-exon genes with or without AEU and single exon genes. Our results indicate that differential expression of AEU could be used as biomarker for GBM and potentially other cancers.

Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival.

BACKGROUND: Glioblastoma is a complex multifactorial disorder that has swift and devastating consequences. Few genes have been consistently identified as prognostic biomarkers of glioblastoma survival. The goal of this study was to identify general and clinical-dependent biomarker genes and biological processes of three complementary events: lifetime, overall and progression-free glioblastoma survival. METHODS: A novel analytical strategy was developed to identify general associations between the biomarkers and glioblastoma, and associations that depend on cohort groups, such as race, gender, and therapy. Gene network inference, cross-validation and functional analyses further supported the identified biomarkers. RESULTS: A total of 61, 47 and 60 gene expression profiles were significantly associated with lifetime, overall, and progression-free survival, respectively. The vast majority of these genes have been previously reported to be associated with glioblastoma (35, 24, and 35 genes, respectively) or with other cancers (10, 19, and 15 genes, respectively) and the rest (16, 4, and 10 genes, respectively) are novel associations. Pik3r1, E2f3, Akr1c3, Csf1, Jag2, Plcg1, Rpl37a, Sod2, Topors, Hras, Mdm2, Camk2g, Fstl1, Il13ra1, Mtap and Tp53 were associated with multiple survival events.Most genes (from 90 to 96%) were associated with survival in a general or cohort-independent manner and thus the same trend is observed across all clinical levels studied. The most extreme associations between profiles and survival were observed for Syne1, Pdcd4, Ighg1, Tgfa, Pla2g7, and Paics. Several genes were found to have a cohort-dependent association with survival and these associations are the basis for individualized prognostic and gene-based therapies. C2, Egfr, Prkcb, Igf2bp3, and Gdf10 had gender-dependent associations; Sox10, Rps20, Rab31, and Vav3 had race-dependent associations; Chi3l1, Prkcb, Polr2d, and Apool had therapy-dependent associations. Biological processes associated glioblastoma survival included morphogenesis, cell cycle, aging, response to stimuli, and programmed cell death. CONCLUSIONS: Known biomarkers of glioblastoma survival were confirmed, and new general and clinical-dependent gene profiles were uncovered. The comparison of biomarkers across glioblastoma phases and functional analyses offered insights into the role of genes. These findings support the development of more accurate and personalized prognostic tools and gene-based therapies that improve the survival and quality of life of individuals afflicted by glioblastoma multiforme.