Performance and immune response of broilers born to breeders of different ages and fed different valine levels

Two experiments were carried out to evaluate the effects of digestible valine supplementation in pre-starter and starter diets on the productivity, nutrient metabolizability coefficient (NMC), and immune response of broilers from breeders of different ages. Experiments I and II were conducted with broilers in the pre-starter (1 to 7 days of age) and starter (8 to 21 days of age) phases, respectively. Broilers were fed diets that differed in their digestible valine content. In each trial, 400 male Cobb 500® chicks were randomly housed in a 2 × 4 factorial arrangement with eight treatments and five replicates of 10 birds each. The main effects were breeder age (37 vs. 52 weeks) and the digestible valine level in pre-starter (9.2, 10.2, 11.2, and 12.2 g/kg) and starter (8.3, 9.3, 10.3, and 11.3 g/kg) diets. Productive performance, intestinal histology, and immune response of broilers were evaluated. Supplementation with 11.2 g/kg valine in pre-starter diets improved NMC and increased villus height and villus:crypt ratio in the duodenum, jejunum development, and lymphocyte proliferation in the spleen of broilers at seven days of age, without improving performance (body weight gain, feed intake, and feed conversion ratio). In the starter phase, valine supplementation reduced feed intake but did not affect NMC, intestinal development, or immune response. The present results suggest that the same level of digestible valine should be used in the diet of broilers born to breeders of different ages, and the use of 9.2 and 8.3 g/kg digestible valine in pre-starter and starter diets, respectively, is sufficient to ensure satisfactory broiler performance. However, to improve the duodenum and jejunum development and immune response of broilers in the pre-starter phase, higher digestible valine levels are required.

High leucine levels affecting valine and isoleucine recommendations in low-protein diets for broiler chickens.

Four experiments were conducted to estimate the optimal standardized ileal digestible (SID) level of branched-chain amino acids in low-protein diets during the starter, grower, and finisher periods, using the response surface methodology, and to study their effects on performance and mRNA expression of genes involved in the mechanistic target of rapamycin (mTOR) pathway of broiler chickens from 8 to 21 D of age. In experiments 1, 2, and 3, a total of 1,500 Cobb male broiler chickens were assigned to 15 diets of a central composite rotatable design (CCD) of response surface methodology containing 5 levels of SID Leu, Val, and Ile with 5 replicate pens of 20 birds each. A 3-factor, 5-level CCD platform was used to fit the second-order polynomial equation of broiler performance. In experiment 4, a total of 540 8-day-old Cobb male broiler chickens were distributed in a completely randomized 2 x 3 x 3 factorial arrangement with 2 SID Leu levels (1.28 or 1.83%), 3 SID Val levels (0.65, 0.90, or 1.20%), and 3 SID Ile levels (0.54, 0.79, or 1.09%) for a total of 18 treatments with 5 replicate cages of 6 birds each. High Leu levels impaired (P < 0.05) gain:feed when birds were fed marginal Val or Ile diets. However, gain:feed was restored when both Val and Ile were supplemented to reach adequate or high levels. High Leu levels increased (P < 0.05) mRNA expression of S6K1 and eEF2 genes only in birds fed high Ile levels. Dietary SID Leu, Val, and Ile levels required for gain:feed optimization in low-protein diets were estimated at 1.37, 0.94, and 0.87% during the starter period; 1.23, 0.82, and 0.75% during the grower period; and 1.15, 0.77, and 0.70% during the finisher phase, respectively. Higher Val and Ile levels are required to optimize the effect of Leu supplementation on mRNA expression of mTOR pathway genes in the pectoralis major muscle of broilers from day 1 to 21 after hatch.

Association between Dietary Habits and Physical Function in Brazilian and Italian Older Women.

The present study investigated and compared the patterns of dietary protein intake and physical function in Brazilian and Italian older women. Seventy-five Brazilian older women were recruited in a community senior center. Fifty-three age-matched Italian older women were selected from participants of the Longevity check-up (Lookup) 7+ study. In both samples, physical performance was evaluated by isometric handgrip strength (IHG) and five-time sit-to-stand (5 × STS) tests, while diet was assessed through 24-h recall. Results indicated that Brazilian women had a higher intake of plant-based protein (52.7% vs. 30.5% kcal), while Italian women consumed greater amounts of animal-derived protein (29.7% vs. 41.5% kcal). In Brazilian women, the binary logistic regression analysis indicated that body weight-adjusted protein consumption was associated with IHG adjusted by body mass index and with 5 × STS performance. In the Italian sample, the intake of isoleucine, leucine, and valine was significantly associated with 5 × STS performance. Our findings indicate that Brazilian and Italian community-dwelling older women show different patterns of protein intake, with higher consumption of plant-based protein in the Brazilian sample and higher ingestion of animal-derived protein in the Italian subgroup. These dietary patterns may differentially impact the relationship between physical function and protein intake observed in Brazilian and Italian older women.

Anti-rod and ring antibodies in patients with chronic hepatitis C using direct-acting antivirals.

Anti-rods and rings (anti-RR) antibody induction is related to the combination of interferon and ribavirin in the treatment of hepatitis C virus (HCV) infection. If the main factor leading to this autoimmune reaction is the combination of these drugs, is not well known, but in vitro studies shows that ribavirin alone can induce rods and rings structures. New direct-acting antivirals (DAAs) permit HCV treatment without needing interferon but may be associated with ribavirin in the most difficult-to-treat patients. The aim of this study is to evaluate the occurrence of anti-RR in patients with chronic HCV infection, before and after 12 weeks of treatment with DAAs, with and without ribavirin. From Jun 2016 to Oct 2017, 52 HCV-infected patients were screened for anti-RR before and after DAA therapy, including sofosbuvir, daclatasvir, simeprevir, and ribavirin. Serum samples were analyzed using indirect immunofluorescence. The anti-RR was present in 11 (21%) of the 52 patients (51.9% male and mean age of 59.1 years) before using DAAs. All of them had been previously treated and previous exposed to interferon/ribavirin, with exposure time to ribavirin associated with the presence of anti-RR. After 12 weeks of DAA treatment, 3 patients (5.7%) developed the antibody in low titers, and two of them (66%) were interferon/ribavirin experienced. Only one of the 29 naïve patients (3.44%) developed anti-RR during the current treatment. Anti-RR was present in patients previously treated with interferon/ribavirin and can emerge after DAA treatment probably at a lower frequency than after interferon/ribavirin treatment.

Tibiotarsus bone characteristics and tibial dyschondroplasia incidence of broilers fed diets supplemented with leucine and valine.

Two experiments were conducted to study the effect of standardized ileal digestible (SID) leucine and valine levels on tibiotarsus bone characteristics and the incidence of tibial dyschondroplasia of broilers from day 1 to 21 (Experiment I) and day 21 to 42 post-hatch (Experiment II). Each experimental phase was evaluated independently. In both experiments, a total of 1,500 one-day-old Cobb 500 male broiler chickens were distributed in a completely randomized design 5 × 5 factorial arrangement for a total of 25 treatments. The SID leucine and valine levels were ranged from 10.0 to 19.6 g/kg, and 6.0 to 12.0 g/kg from day 1 to 21 post-hatch, respectively, while day 21 to 42 post-hatch ranged from 10.0 to 18.0 g leucine/kg, and 5.2 to 11.2 g valine/kg. Serum calcium and phosphorus, bone concentrations of calcium, phosphorus and ash, diameter and Seedor index of the tibiotarsus were not affected (p > .05) by the treatments at 21 or 42 days of age. There was an interaction (p ≤.06) between the SID levels of leucine and valine on tibiotarsus breaking strength at 21 days, but not at 42 days of age (p > .05). Tibiotarsus breaking strength was maximized in broilers from day 1 to 21 with the dietary levels of leucine and valine at 14.2 and 9.0 g/kg respectively. Dietary leucine levels reduced linearly (p < .05) the hypertrophic zone of tibiotarsus cartilage at 21 days of age. Therefore, leucine and valine supplementation interact positively on bone strength of broilers from day 1 to 21 post-hatch. Leucine can be a useful amino acid for reducing the hypertrophic cartilage zone in broilers from day 1 to 21, but not from day 21 to 42 post-hatch.

Leucine and valine supplementation of low-protein diets for broiler chickens from 21 to 42 days of age.

The objective of this study was to determine the requirements and interactions between the standardized ileal digestible (SID) Leu and Val levels in low-protein diets, and their effects on performance, serum characteristics, carcass yield and diameter of muscle fibers of broiler chickens from d 21 to 42 posthatch. A total of 1,500 21-day-old Cobb 500 male broiler chickens were distributed in a completely randomized design in a 5 × 5 factorial arrangement for a total of 25 treatments with 3 replicates of 20 birds each. Treatments consisted of 5 SID Leu levels (1.0, 1.2, 1.4, 1.6, or 1.8%) and 5 SID Val levels (0.52, 0.67, 0.82, 0.97, or 1.12%). At 42 d of age, there was interaction (P < 0.05) between the SID levels of Leu and Val on feed intake and weight gain. There was a quadratic effect (P < 0.05) of Leu and Val levels on feed conversion, with minimal point estimated at the levels of 1.19 and 0.86%, respectively. Dietary Leu supplementation reduced linearly (P < 0.05) serum concentrations of triglycerides and ß-hydroxybutyrate. Dietary Leu increased (P ≤ 0.05) the fiber diameters of the pectoralis major muscle and breast yield at the levels of 1.24 and 1.13%, respectively, while the thigh yield was improved with the level of 0.71% Val. Abdominal fat decreased linearly (P < 0.05) with increasing levels of dietary Leu and Val. The SID Leu and Val levels needed to optimize weight gain and feed conversion in low-CP diets for broiler chickens from d 21 to 42 posthatch were estimated at 1.15 and 0.86%, and 1.19 and 0.86%, respectively. The supplementation of Leu and Val can reduce the abdominal fat deposition in birds fed low-CP diets during the grower phase. Leu and Val interactions can influence the performance but not the serum characteristics, carcass yield and diameter of muscle fibers of broilers fed low-protein diets. Therefore, it is necessary to consider the dietary Leu content to estimate the ideal level of Val in low-CP diets for optimum broiler performance.

Exigência de valina e isoleucina para codornas de corte no período de um a 14 dias e de 15 a 35 dias de idade / Valine and isoleucine requirement for meat quails in the period of 1 to 14 days and of 15 to 35 days old

Two experiments were carried out in order to estimate the requirements of digestible valine and isoleucine for growing meat quails. In experiment 1, 2160 meat quails with 1 day of age, not sexed, were used, distributed in a completely randomized design with a 4x4 factorial arrangement, with four levels of digestible valine (0.90, 1.10, 1.30, and 1.50%) and four levels of digestible isoleucine (0.80, 1.00, 1.20, and 1.40 %), totaling 16 treatments with three replications and 45 quails per experimental unit. The body weight, the weight gain, and the accumulated body biomass linearly increased in function of digestible valine levels and were influenced in a quadratic way estimating 1.38% of digestible isoleucine. In experiment 2, 1440 meat quails, not sexed, were used, distributed in a completely randomized design with a 4x4 factorial arrangement, with four levels of digestible valine (0.82, 1.02, 1.22, and 1.42%) and four levels of digestible isoleucine (0.73, 0.93, 1.13, and 1.33%), totaling 16 treatments with three replications and 30 quails per experimental unit. The performance of meat quails from 15 to 35 days of age was not affected by increased levels of digestible valine and digestible isoleucine in the experimental diets. It was concluded that the requirements of digestible valine and digestible isoleucine for maximum performance of meat quail from one to 14 days of age were 1.50% and 1.38%, respectively, corresponding to relations: valine: lysine of 95% and isoleucine: lysine of 88%. The lower levels evaluated, in the period of 15 to 35 days old, 0.82% digestible valine and 0.73% of digestible isoleucine, corresponding to relations valine: lysine of 52% and isoleucine: lysine of 46% were sufficient to meet the nutritional requirements of meat quails without compromising performance.(AU)

Foram conduzidos dois experimentos, com o objetivo de estimar a exigência de valina e isoleucina digestível para codornas de corte em crescimento. No experimento 1, foram utilizadas 2.160 codornas de corte de um dia de idade, não sexadas, distribuídas em um delineamento inteiramente ao acaso, com arranjo fatorial 4x4, sendo quatro níveis de valina digestível (0,90, 1,10, 1,30 e 1,50%) e quatro níveis de isoleucina digestível (0,80, 1,00, 1,20 e 1,40%), totalizando 16 tratamentos, com três repetições e 45 codornas por unidade experimental. O peso corporal, o ganho de peso e a biomassa corporal acumulada aumentaram linearmente em função dos níveis de valina digestível e foram influenciados de forma quadrática, estimando 1,38% de isoleucina digestível. No experimento 2, foram utilizadas 1.440 codornas de corte não sexadas, distribuídas em um delineamento inteiramente ao acaso, com arranjo fatorial 4x4, sendo quatro níveis de valina digestível (0,82, 1,02, 1,22 e 1,42%) e quatro níveis de isoleucina digestível (0,73, 0,93, 1,13 e 1,33%), totalizando 16 tratamentos, com três repetições e 30 codornas por unidade experimental. O desempenho de codornas de corte, no período de 15 a 35 dias de idade, não foi influenciado pelo aumento dos níveis de valina e isoleucina digestível nas rações experimentais. Conclui-se que as exigências de valina e isoleucina digestível para o máximo desempenho de codornas de corte, no período de um a 14 dias de idade, foram de 1,50% e 1,38%, respectivamente, correspondendo às relações valina:lisina de 95% e isoleucina:lisina de 88%. Os menores níveis avaliados, no período de 15 a 35 dias de idade, de 0,82% de valina digestível e de 0,73% de isoleucina digestível, correspondendo às relações valina:lisina de 52% e isoleucina: lisina de 46%, foram suficientes para satisfazer as exigências nutricionais das codornas de corte sem comprometer o desempenho.(AU)

Exigência de valina e isoleucina para codornas de corte no período de um a 14 dias e de 15 a 35 dias de idade / Valine and isoleucine requirement for meat quails in the period of 1 to 14 days and of 15 to 35 days old

Foram conduzidos dois experimentos, com o objetivo de estimar a exigência de valina e isoleucina digestível para codornas de corte em crescimento. No experimento 1, foram utilizadas 2.160 codornas de corte de um dia de idade, não sexadas, distribuídas em um delineamento inteiramente ao acaso, com arranjo fatorial 4x4, sendo quatro níveis de valina digestível (0,90, 1,10, 1,30 e 1,50%) e quatro níveis de isoleucina digestível (0,80, 1,00, 1,20 e 1,40%), totalizando 16 tratamentos, com três repetições e 45 codornas por unidade experimental. O peso corporal, o ganho de peso e a biomassa corporal acumulada aumentaram linearmente em função dos níveis de valina digestível e foram influenciados de forma quadrática, estimando 1,38% de isoleucina digestível. No experimento 2, foram utilizadas 1.440 codornas de corte não sexadas, distribuídas em um delineamento inteiramente ao acaso, com arranjo fatorial 4x4, sendo quatro níveis de valina digestível (0,82, 1,02, 1,22 e 1,42%) e quatro níveis de isoleucina digestível (0,73, 0,93, 1,13 e 1,33%), totalizando 16 tratamentos, com três repetições e 30 codornas por unidade experimental. O desempenho de codornas de corte, no período de 15 a 35 dias de idade, não foi influenciado pelo aumento dos níveis de valina e isoleucina digestível nas rações experimentais. Conclui-se que as exigências de valina e isoleucina digestível para o máximo desempenho de codornas de corte, no período de um a 14 dias de idade, foram de 1,50% e 1,38%, respectivamente, correspondendo às relações valina:lisina de 95% e isoleucina:lisina de 88%. Os menores níveis avaliados, no período de 15 a 35 dias de idade, de 0,82% de valina digestível e de 0,73% de isoleucina digestível, correspondendo às relações valina:lisina de 52% e isoleucina: lisina de 46%, foram suficientes para satisfazer as exigências nutricionais das codornas de corte sem comprometer o desempenho.(AU)

Two experiments were carried out in order to estimate the requirements of digestible valine and isoleucine for growing meat quails. In experiment 1, 2160 meat quails with 1 day of age, not sexed, were used, distributed in a completely randomized design with a 4x4 factorial arrangement, with four levels of digestible valine (0.90, 1.10, 1.30, and 1.50%) and four levels of digestible isoleucine (0.80, 1.00, 1.20, and 1.40 %), totaling 16 treatments with three replications and 45 quails per experimental unit. The body weight, the weight gain, and the accumulated body biomass linearly increased in function of digestible valine levels and were influenced in a quadratic way estimating 1.38% of digestible isoleucine. In experiment 2, 1440 meat quails, not sexed, were used, distributed in a completely randomized design with a 4x4 factorial arrangement, with four levels of digestible valine (0.82, 1.02, 1.22, and 1.42%) and four levels of digestible isoleucine (0.73, 0.93, 1.13, and 1.33%), totaling 16 treatments with three replications and 30 quails per experimental unit. The performance of meat quails from 15 to 35 days of age was not affected by increased levels of digestible valine and digestible isoleucine in the experimental diets. It was concluded that the requirements of digestible valine and digestible isoleucine for maximum performance of meat quail from one to 14 days of age were 1.50% and 1.38%, respectively, corresponding to relations: valine: lysine of 95% and isoleucine: lysine of 88%. The lower levels evaluated, in the period of 15 to 35 days old, 0.82% digestible valine and 0.73% of digestible isoleucine, corresponding to relations valine: lysine of 52% and isoleucine: lysine of 46% were sufficient to meet the nutritional requirements of meat quails without compromising performance.(AU)

Desempenho e rendimento de carcaça em frangos de corte de um a 46 dias alimentados com dietas contendo diferentes níveis de valina e reduzido teor proteico / Performance and carcass yield of broilers from 1 to 46 days fed diets containing different levels of valine and reduced protein content

Este estudo teve como objetivo avaliar as relações de valina:lisina digestíveis em dietas com teor reduzido de proteína bruta (PB) e os efeitos dessa redução sobre desempenho e rendimento de carcaça em frangos de corte. Foram utilizados 1200 pintos machos seguindo modelo inteiramente ao acaso, com seis tratamentos de seis repetições (exceto controle, com 10 repetições), compostos por 30 aves cada. O tratamento controle (T1) foi formulado conforme os níveis de proteína bruta e aminoácidos (AAs) recomendados por Rostagno et al . (2011), e os demais tratamentos (T2 a T6) tiveram seus níveis de PB reduzidos (4% em relação ao controle) e variaram em função da relação valina:lisina digestíveis, com cinco níveis equidistantes em intervalos de 0,07:1, variando de 0,63:1 e 0,91:1 (dietas até 21 dias) e de 0,64:1 e 0,92:1 (dietas após 21 dias). As seguintes características de desempenho foram avaliadas: ganho de peso, consumo de ração, conversão alimentar, viabilidade criatória e índice de eficiência produtiva. Aos 46 dias de idade, seis animais por repetição foram abatidos para determinação de rendimento de carcaça e de cortes comerciais. As diferentes relações valina:lisina digestíveis não influenciaram o desempenho dos animais (P>0,05) para nenhuma característica avaliada. A redução proteica piorou a conversão alimentar dos animais (P≤0,05) até os 21 dias. Os resultados sugerem que os níveis de valina utilizados não afetam o desempenho dos animais, apenas o rendimento de peito e que, portanto, a redução proteica não é recomendada durante as três primeiras semanas de criação(AU)

This study aimed to evaluate valine:lysine ratios in diets with reduced content of crude protein and the effects of this reduction on the performance of broiler chickens. 1200 male chicks were used following a complete randomized design with six replicates of six treatments (except control, with 10 replicates), each one with 30 chicks. The control treatment (T1) was formulated following levels of crude protein (CP) and the amino acids (AAs) recommended by Rostagno et al. (2011), and the other treatments (T2 to T6) had reduced levels of CP (4 % compared to control) and varied in proportion valine:lysine, with 5 levels at equidistant intervals 0.07:1 ranging from 0.63:1 to 0.91:1 (up to 21 days) and from 0.64:1 to 0.92:1 (after 21 days). The performance characteristics measured were: weight gain, feed intake, feed conversion, viability and productive efficiency index. At 46 days six animals per replicate were slaughtered for evaluation of carcass and commercial cuts. The different valine:lysine ratios did not affect animal performance (P>0.05). Reducing protein impaired feed conversion (P≤.05) up to 21 days. The results suggest that levels of valine used did not affect the broilers' performance, however, breast meat yield and reduced protein are not recommended during the first three weeks(AU)

Desempenho e rendimento de carcaça em frangos de corte de um a 46 dias alimentados com dietas contendo diferentes níveis de valina e reduzido teor proteico / Performance and carcass yield of broilers from 1 to 46 days fed diets containing different levels of valine and reduced protein content

Este estudo teve como objetivo avaliar as relações de valina:lisina digestíveis em dietas com teor reduzido de proteína bruta (PB) e os efeitos dessa redução sobre desempenho e rendimento de carcaça em frangos de corte. Foram utilizados 1200 pintos machos seguindo modelo inteiramente ao acaso, com seis tratamentos de seis repetições (exceto controle, com 10 repetições), compostos por 30 aves cada. O tratamento controle (T1) foi formulado conforme os níveis de proteína bruta e aminoácidos (AAs) recomendados por Rostagno et al . (2011), e os demais tratamentos (T2 a T6) tiveram seus níveis de PB reduzidos (4% em relação ao controle) e variaram em função da relação valina:lisina digestíveis, com cinco níveis equidistantes em intervalos de 0,07:1, variando de 0,63:1 e 0,91:1 (dietas até 21 dias) e de 0,64:1 e 0,92:1 (dietas após 21 dias). As seguintes características de desempenho foram avaliadas: ganho de peso, consumo de ração, conversão alimentar, viabilidade criatória e índice de eficiência produtiva. Aos 46 dias de idade, seis animais por repetição foram abatidos para determinação de rendimento de carcaça e de cortes comerciais. As diferentes relações valina:lisina digestíveis não influenciaram o desempenho dos animais (P>0,05) para nenhuma característica avaliada. A redução proteica piorou a conversão alimentar dos animais (P≤0,05) até os 21 dias. Os resultados sugerem que os níveis de valina utilizados não afetam o desempenho dos animais, apenas o rendimento de peito e que, portanto, a redução proteica não é recomendada durante as três primeiras semanas de criação.

This study aimed to evaluate valine:lysine ratios in diets with reduced content of crude protein and the effects of this reduction on the performance of broiler chickens. 1200 male chicks were used following a complete randomized design with six replicates of six treatments (except control, with 10 replicates), each one with 30 chicks. The control treatment (T1) was formulated following levels of crude protein (CP) and the amino acids (AAs) recommended by Rostagno et al. (2011), and the other treatments (T2 to T6) had reduced levels of CP (4 % compared to control) and varied in proportion valine:lysine, with 5 levels at equidistant intervals 0.07:1 ranging from 0.63:1 to 0.91:1 (up to 21 days) and from 0.64:1 to 0.92:1 (after 21 days). The performance characteristics measured were: weight gain, feed intake, feed conversion, viability and productive efficiency index. At 46 days six animals per replicate were slaughtered for evaluation of carcass and commercial cuts. The different valine:lysine ratios did not affect animal performance (P>0.05). Reducing protein impaired feed conversion (P≤.05) up to 21 days. The results suggest that levels of valine used did not affect the broilers' performance, however, breast meat yield and reduced protein are not recommended during the first three weeks.

Dorsal medial prefrontal cortex contributes to conditioned taste aversion memory consolidation and retrieval.

The medial prefrontal cortex (mPFC) is known for its role in decision making and memory processing, including the participation in the formation of extinction memories. However, little is known regarding its contribution to aversive memory consolidation. Here we demonstrate that neural activity and protein synthesis are required in the dorsal mPFC for memory formation of a conditioned taste aversion (CTA) task and that this region is involved in the retrieval of recent and remote long-term CTA memory. In addition, both NMDA receptor and CaMKII activity in dorsal mPFC are needed for CTA memory consolidation, highlighting the complexity of mPFC functions.

Venous thromboembolism and cardiovascular risk: results from the NAVIGATOR trial.

BACKGROUND: Contemporary studies suggest an association between venous thromboembolism and a higher incidence of major cardiovascular events, mostly attributed to arterial atherothrombosis. Using data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, we assessed the association of venous thromboembolism with major cardiovascular events. METHODS: In NAVIGATOR, patients with impaired glucose tolerance were randomly allocated to receive valsartan or placebo and nateglinide or placebo in addition to lifestyle modification. Baseline characteristics and prior history of venous thromboembolism were assessed. After adjusting for important baseline covariates, Cox proportional hazards regression models were used to assess the association between venous thromboembolism and major cardiovascular outcomes. RESULTS: Of the 9306 patients enrolled, 129 (1.4%) had a history of venous thromboembolism. Patients with venous thromboembolism were older, more frequently white and female, and had a higher body mass index. Patients with venous thromboembolism had higher 5-year event rates for the composite of death, myocardial infarction, and stroke, as compared with patients without venous thromboembolism (10.7% vs 5.9%; P < .001; adjusted hazard ratio 2.12; 95% confidence interval, 1.36-3.31; P = .001). CONCLUSION: In patients with impaired glucose tolerance at high risk for cardiovascular events, the prevalence of venous thromboembolism was rare but associated with worse long-term cardiovascular outcomes, including arterial events. Venous thromboembolism is a marker of risk, and attention should be paid to this high-risk group of patients.

Digestible valine requirements for broilers from 22 and 42 days old / Exigências em valina digestível para frangos de corte de 22 a 42 dias de idade

Current experiment established different criteria to evaluate the requirements of digestible valine for broilers from 22 and 42 days of age, by different regression models (quadratic, exponential and Linear Response Plateau) and, in the case of statistical significance, the comparison of means by Duncantest at 5% probability. A total of 1,920 Cobb 500 male broilers were used and distributed in an entirely randomized experimental design, with 6 treatments (6 digestible valine levels: 0.7192, 0.7729, 0.8265, 0.8802, 0.9339 and 0.9876%) and 8 replications, with 40 broilers each. Data on performance and carcass characteristics were evaluated. The level of 0.8265% digestible valine was considered standard. The inclusion of 0.816, 0.848 and 0.903% of digestible valine levels, corresponding to digestible valine:lysine ratios of approximately 76.00%, 79.00% and 84.12%, provided best feed intake, weight gain and feed conversion ratio, respectively for broiler from 22 to 42 days of age.

Um experimento foi realizado com o objetivo de estabelecer critérios de avaliação das exigências de valina digestível para frangos de corte de 22 a 42 dias de idade utilizando-se diferentes modelos de regressão (quadrático, exponencial e de retas segmentadas ou Linear Response Plateau). Foram utilizados 1.920 frangos de corte machos com 22 dias de idade, distribuídos em delineamento inteiramente ao acaso, com seis tratamentos (6 níveis de valina digestível: 0,7192; 0,7729; 0,8265; 0,8802; 0,9339 e 0,9876) e oito repetições de 40 aves. Utilizou-se como padrão o nível de 0,8265% de valina digestível. A inclusão dos níveis 0,8160; 0,8484 e 0,9031% de valina digestível proporcionou os melhores resultados de consumo de ração, ganho de peso e conversão alimentar respectivamente.

Digestible valine requirements for broilers from 22 and 42 days old / Exigências em valina digestível para frangos de corte de 22 a 42 dias de idade

Current experiment established different criteria to evaluate the requirements of digestible valine for broilers from 22 and 42 days of age, by different regression models (quadratic, exponential and Linear Response Plateau) and, in the case of statistical significance, the comparison of means by Duncantest at 5% probability. A total of 1,920 Cobb 500 male broilers were used and distributed in an entirely randomized experimental design, with 6 treatments (6 digestible valine levels: 0.7192, 0.7729, 0.8265, 0.8802, 0.9339 and 0.9876%) and 8 replications, with 40 broilers each. Data on performance and carcass characteristics were evaluated. The level of 0.8265% digestible valine was considered standard. The inclusion of 0.816, 0.848 and 0.903% of digestible valine levels, corresponding to digestible valine:lysine ratios of approximately 76.00%, 79.00% and 84.12%, provided best feed intake, weight gain and feed conversion ratio, respectively for broiler from 22 to 42 days of age.(AU)

Um experimento foi realizado com o objetivo de estabelecer critérios de avaliação das exigências de valina digestível para frangos de corte de 22 a 42 dias de idade utilizando-se diferentes modelos de regressão (quadrático, exponencial e de retas segmentadas ou Linear Response Plateau). Foram utilizados 1.920 frangos de corte machos com 22 dias de idade, distribuídos em delineamento inteiramente ao acaso, com seis tratamentos (6 níveis de valina digestível: 0,7192; 0,7729; 0,8265; 0,8802; 0,9339 e 0,9876) e oito repetições de 40 aves. Utilizou-se como padrão o nível de 0,8265% de valina digestível. A inclusão dos níveis 0,8160; 0,8484 e 0,9031% de valina digestível proporcionou os melhores resultados de consumo de ração, ganho de peso e conversão alimentar respectivamente.(AU)

A double-blind, randomized, placebo-controlled study to assess the safety, antiviral activity and pharmacokinetics of GSK2336805 when given as monotherapy and in combination with peginterferon alfa-2a and ribavirin in hepatitis C virus genotype 1-infected treatment-naive subjects.

BACKGROUND & AIMS: GSK2336805 is a HCV NS5A inhibitor for chronic hepatitis C (CHC). In a prior Phase I study, GSK2336805 was well tolerated and had an antiviral and pharmacokinetic profile suitable for once-daily administration. This 28-day, double-blind, randomized, placebo-controlled study evaluated once daily GSK2336805 60 mg alone or in combination with peginterferon alfa-2a (180 µg per week) and ribavirin (1000-1200 mg daily) (PEG/RIBA) in treatment-naive genotype 1 CHC subjects. METHODS: Five centres enrolled 16 subjects in the USA and Puerto Rico who received GSK2336805 + PEG/RIBA or placebo + PEG/RIBA. RESULTS: Following a single monotherapy dose of GSK2336805 on day 1, median reduction from baseline in HCV RNA was -2.96 log10 (N = 11) vs. -0.13 log10 (N = 4) for placebo. With the addition of PEG/RIBA on day 2, subjects receiving GSK2336805 exhibited greater decreases in viral load over the 28-day treatment period as compared with placebo. At day 28, median reduction from baseline was -4.86 log10 (N = 9) in the GSK2336805 + PEG/RIBA group as compared with -1.98 log10 (N = 4) in the placebo + PEG/RIBA group. At day 28, rapid virological response (RVR) occurred in 8/11 (73%) of the GSK2336805 + PEG/RIBA subjects as compared with 1/4 (25%) of the placebo + PEG/RIBA subjects. Adverse events were consistent with those reported in clinical trials of peginterferon and ribavirin, and no unique adverse events appeared to be associated with GSK2336805. CONCLUSIONS: GSK2336805 is a potent NS5A inhibitor that showed a substantial antiviral effect as a monotherapy and in combination with peginterferon and ribavirin. ClinicalTrials.gov Identifier: NCT01439373.

Relações valina: lisina disgestíveis em dietas com nível de proteína bruta reduzido em frangos de corte / Relations valine: lysine digestible in diets with reduced crude protein level in broilers

Este estudo teve como objetivo avaliar relações de valina:lisina digestíveis em dietas com teor reduzido de proteína bruta e os efeitos desta redução sobre desempenho e rendimento de carcaça em frangos de corte. Foram utilizados 1200 pintos machos de um dia de idade, seguindo modelo inteiramente casualizado, com seis tratamentos de seis repetições (exceto controle, com 10 repetições), compostos por 30 aves cada. O tratamento controle (T1) foi formulado seguindo os níveis de proteína bruta (PB) e aminoácidos (AAs) recomendados e os demais tratamentos (T2 a T6) tiveram seus níveis de PB reduzidos (4% em relação ao controle) e variaram em função da relação valina:lisina digestíveis, com 5 níveis equidistantes com intervalos de 0,07:1, variando de 0,63:1 e 0,91:1 em dietas até 21 dias, e 0,64:1 e 0,92:1 em dietas após 21 dias, respectivamente. Foram mensurados as seguintes características de desempenho: ganho de peso, consumo de ração, conversão alimentar, viabilidade criatória e índice de eficiência produtiva. Aos 46 dias de idade seis animais por repetição foram abatidos para determinação de rendimento de carcaça e de cortes comerciais. A cama também foi colhida no começo e final do experimento e seus níveis de nitrogênio analisados para determinação do nitrogênio excretado. As diferentes relações valina:lisina digestíveis não influenciaram o desempenho dos animais (P>0,05), porém afetaram o rendimento de peito, com relação ótima de valina:lisina digestíveis de 0,75. A redução proteica piorou o desempenho dos animais (P≤0,05) durante as primeiras três semanas de criação. Porém após este período tal prejuízo no desempenho não é visualizado.

This study aimed to evaluate relationships valine: lysine in diets with reduced content of crude protein and the effects of this reduction on performance and carcass yield of broiler chickens. Male chicks were used in 1200 than a day old, following complete randomized design with six treatments with six replications (except control, with 10 repetitions), composed of 30 chicks each. The control treatment (T1) was formulated following levels of crude protein (CP) and amino acids (AAs) and other recommended treatments (T2 to T6) had reduced levels of CP (4% compared to control) and varied according the ratio valine: lysine with 5 levels of 0,07:1 equidistant intervals ranging from 0,63:1 and 0,91:1 in the diet up to 21 days, and 0.92 0,64:1: 1 after 21 days on diets, respectively. We measured the following performance characteristics: weight gain, feed intake, feed conversion, viability and productive efficiency. At 46 days of age six animals per replicate were slaughtered for determination of carcass and commercial cuts. The bed was also collected at the beginning and end of the experiment and their levels of nitrogen analyzed for nitrogen excreted. The different relationships valine: lysine did not affect animal performance (P> 0.05), but they affected breast yield, compared with optimal valine: lysine 0.75. Reducing protein worsened performance of animals (P ≤ 0.05) during the first three weeks of creation. But after this period such impairment in performance is not displayed.

Memory reconsolidation allows the consolidation of a concomitant weak learning through a synaptic tagging and capture mechanism.

Motivated by the synaptic tagging and capture (STC) hypothesis, it was recently shown that a weak learning, only able to produce short-term memory (STM), can succeed in establishing long-term memory (LTM) with a concomitant, stronger experience. This is consistent with the capture, by the first-tagged event, of the so-called plasticity-related proteins (PRPs) provided by the second one. Here, we describe how a concomitant session of reactivation/reconsolidation of a stronger, contextual fear conditioning (CFC) memory, allowed LTM to result from a weak spatial object recognition (wSOR) training. Consistent with an STC process, the effect was observed only during a critical time window and was dependent on the CFC reconsolidation-related protein synthesis. Retrieval by itself (without reconsolidation) did not have the same promoting effect. We also found that the inactivation of the NMDA receptor by AP5 prevented wSOR training to receive this support of CFC reconsolidation (supposedly through the production of PRPs), which may be the equivalent of blocking the setting of a learning tag in the dorsal CA1 region for that task. Furthermore, either a Water Maze reconsolidation, or a CFC extinction session, allowed the formation of wSOR-LTM. These results suggest for the first time that a reconsolidation session can promote the consolidation of a concomitant weak learning through a probable STC mechanism. These findings allow new insights concerning the influence of reconsolidation in the acquisition of memories of otherwise unrelated events during daily life situations.

Aliskiren improves left ventricular dysfunction and reduces cardiac dilation in Syrian cardiomyopathic hamsters.

OBJECTIVE: Chronic activation of the renin-angiotensin-aldosterone system is a major contributing factor to the pathogenesis and progression of cardiovascular and renal diseases. METHODS: To evaluate the role of renin-angiotensin-aldosterone system blockade with aliskiren, a direct renin inhibitor, in the development and progression of dilated cardiomyopathy in the Syrian cardiomyopathic hamster (SCH) model, we treated 1-month-old SCH with aliskiren (10 mg·kg·d) over a 4-month period. For comparative purposes, we also evaluated the effects of the angiotensin receptor blocker valsartan (10 mg·kg·d) and the combination of both drugs. Age-matched golden hamsters were used as controls. Left ventricular end-diastolic volume and end-systolic volume, ejection fraction, and diastolic function were determined by echocardiography. Systolic blood pressure (SBP) was also measured in the left femoral artery by sphygmomanometry. RESULTS: Results indicate that at 2 months of age, SBP is higher in SCH than in controls, and administration for 1 month of aliskiren, valsartan, or the combination of these drugs normalized SBP in SCH to a similar extent. In 5-month-old SCH, aliskiren improved ejection fraction (from 48.6% ± 5.8% to 69.4% ± 3.2%, n = 5, P < 0.05), left ventricular end-systolic volume (from 0.28 ± 0.06 to 0.10 ± 0.01 mL/100 g body weight), left ventricular end-diastolic volume (from 0.61 ± 0.05 to 0.34 ± 0.02 mL/100 g body weight), and normalized diastolic function (E:A ratio increases from 0.93 ± 0.13 to 1.70 ± 0.03, n = 5, P < 0.05). Similar results were observed with valsartan or the combination of aliskiren and valsartan. CONCLUSIONS: Our results indicate that in this animal model, aliskiren is as effective as valsartan, or the combination of both drugs, in improving diastolic function and in preventing the development of dilated cardiomyopathy. These findings suggest that aliskiren may be used as a monotherapy in heart failure management. Clinical studies, however, are needed to assess the effectiveness of this drug in patients with heart failure.

Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons.

Recent in vitro studies suggest that acyclovir may directly inhibit HIV-1 replication and can select for a specific HIV-1 reverse transcriptase mutation (V75I) with concomitant loss of an anti-HIV-1 effect. We tested for HIV-1 genotypic resistance at reverse transcriptase codon 75 in plasma from 168 HIV-1-infected persons from Botswana, Kenya, Peru, and the United States taking daily acyclovir or valacyclovir for between 8 weeks and 24 months. No V75I cases were detected (95% confidence interval, 0%-2.2%). These prospective in vivo studies suggest that standard-dose acyclovir or valacyclovir does not select for HIV-1 resistance.

An international, randomized, double-blind, placebo-controlled, study of valacyclovir for the suppression of herpes simplex virus type 2 genital herpes in newly diagnosed patients.

BACKGROUND: Antiviral suppressive therapy of genital herpes is often initiated based on the established pattern of recurrences in an individual. Because most persons with first episode herpes simplex virus type 2 (HSV-2) infection experience recurrences and because viral shedding occurs frequently in the first year after infection, we examined the strategy of initiating suppressive therapy shortly after diagnosis of genital HSV-2 infection. SUBJECTS AND METHODS: From June 16, 2004 to July 26, 2006, 384 subjects from 74 sites in the United States, Canada, Argentina, Brazil, and Chile who were newly diagnosed with a first recognized episode of genital herpes at the time of the screening visit or within 3 months before the screening visit were randomized (2:1) to receive valacyclovir 1 g once daily or placebo for 24 weeks. Subjects were instructed to return to clinic during suspected genital herpes outbreaks for clinician confirmation of recurrences. RESULTS: Valacyclovir significantly prolonged the time to first recurrence of HSV-2 genital herpes in newly diagnosed subjects compared with placebo, with approximately 43% of subjects on placebo and 71% of subjects on valacyclovir recurrence-free at 24 weeks (P <0.001). Valacyclovir significantly reduced the mean number of genital HSV-2 recurrences per month occurring during the 24-week study period (0.11 for valacyclovir, 0.48 for placebo, P <0.001). Adverse events were comparable in the valacyclovir and placebo arms. CONCLUSION: Valacyclovir 1 g once daily administered for 24 weeks was well-tolerated and effective in suppressing genital herpes recurrences in immunocompetent newly diagnosed persons without an established recurrence pattern.