CP Levels Research Articles

Abstract P3-02-02: Targeting the tumor microenvironment: A phase II study of copper-depletion using tetrathiomolybdate (TM) in patients (pts) with breast cancer (BC) at high risk for recurrence

Abstract Background: Bone marrow derived VEGFR2+ endothelial progenitor cells (EPCs) and copper-dependent pathways, including lysyl oxidase (LOX), are critical components to remodeling the tumor microenvironment and establishing the pre-metastatic niche. In preclinical models, it has been well established that copper depletion (CD) inhibits tumor progression. We hypothesized that TM-associated CD would reduce EPCs and other copper dependent processes in the pre-metastatic niche in BC pts at high risk for relapse. We investigated the relationship between CD and its effect on EPCs and other components of the tumor microenvironment including LOX, an enzyme critical for cross-linkage of collagen and priming the pre-metastatic niche. Methods: In this single arm, phase II study, BC pts at high risk for recurrence, defined as node+ triple negative (TN), stage 3 and 4 with no evidence of disease (NED) were enrolled on a trial of CD with TM. Pts received oral TM to maintain ceruloplasmin (Cp) between 5-17 mg/dl for 2 years on the primary study. The primary endpoint was change in EPCs measured by flow cytometry before and during treatment with TM. Secondary endpoints included tolerability, safety and effect of copper depletion on other markers including LOX, quantified by ELISA. Results: We enrolled 75 pts. The study treatment duration was 24 cycles (each cycle is 28 days). Over 2200 cycles have been administered. The median age is 51 (range 29-66). 45 pts have Stage 2/3 BC and 30 are Stage 4 NED. TNBC pts represent 48%, and 40% of pts are Stage 4 NED. Median Cp level decreased from 28 at baseline to 15.5 (p<0.0001) after one cycle. Copper depletion was most efficient in TNBC, with 91% achieving a target CP within 4 weeks. TM was well tolerated and the only grade 3/4 toxicities were reversible neutropenia (3.2%) and anemia (0.0005%). CD was associated with a significant decrease in EPCs (p=0.0014) and LOX (p<0.001). At a median follow-up of 5.4 years, the PFS for all 75 pts from the start of TM treatment was 71%, including a PFS of 90% for all stage 2/3 pts with TNBC. The overall survival of all patients enrolled in the trial is 86%. Relapse after two years is a rare event. Conclusions: TM is safe, well tolerated and appears to affect multiple copper dependent biologic processes in the tumor microenvironment known to be important for tumor progression. This seems to be most striking in TNBC. We believe, further phase III trials in a high risk for relapse population are warranted. Citation Format: Nackos E, Willis A, Kornhauser N, Ward M, Andreopoulou E, Cigler T, Moore A, Fitzpatrick V, Cobham M, Schneider S, Wiener A, Guillaume-Abraham J, Warren JD, Rubinchik A, Lane M, Mittal V, Vahdat L. Targeting the tumor microenvironment: A phase II study of copper-depletion using tetrathiomolybdate (TM) in patients (pts) with breast cancer (BC) at high risk for recurrence. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-02-02.

Performance based evaluation of RC coupled shear wall system with steel coupling beam

Steel coupling beam in reinforced concrete (RC) coupled shear wall system is a proper substitute for deep concrete coupling beam. Previous studies have shown that RC coupled walls with steel or concrete coupling beam designed with strength-based design approach, may not guarantee a ductile behavior of a coupled shear wall system. Therefore, seismic performance evaluation of RC coupled shear wall with steel or concrete coupling beam designed based on a strength-based design approach is essential. In this paper first, buildings with 7, 14 and 21 stories containing RC coupled shear wall system with concrete and steel coupling beams were designed with strength-based design approach, then performance level of these buildings were evaluated under two spectrum; Design Basis Earthquake (DBE) and Maximum Considered Earthquake (MCE). The performance level of LS and CP of all buildings were satisfied under DBE and MCE respectively. In spite of the steel coupling beam, concrete coupling beam in RC coupled shear wall acts like a fuse under strong ground motion.

Reducing crude protein and rumen degradable protein with a constant concentration of rumen undegradable protein in the diet of dairy cows: Production performance, nutrient digestibility, nitrogen efficiency, and blood metabolites.

The goals of ruminant protein nutrition are to provide adequate amounts of RDP for optimal ruminal efficiency and to obtain the desired animal productivity with a minimum amount of dietary CP. The aim of the present study was to examine effects of decreasing dietary protein by decreasing RDP with the optimum concentration of RUP on production performance, nutrient digestibility, N retention, rumen fermentation parameters, and blood metabolites in high-producing Holstein cows in early lactation. Nine multiparous lactating cows (second parities, averaging 50 ± 12 d in milk and milk yield of 48 ± 5 kg/d) were used in a triplicate 3 × 3 Latin square design with 3 rations: 1) a total mixed ration (TMR) containing 16.4% CP (10.9% RDP based on DM), 2) a TMR containing 15.6% CP (10% RDP), and 3) a TMR containing 14.8% CP (9.3% RDP). The level of RUP was constant at 5.5% DM across the treatments. All diets were calculated to supply a postruminal lysine to methionine ratio of about 3:1. Dry matter intake, milk yield and composition, 4% fat-corrected milk, and energy-corrected milk were not significantly affected by decreasing dietary CP and RDP levels. Cows fed 16.4% CP diets had greater ( < 0.01) CP and RDP intakes, which resulted in a trend toward greater concentrations of plasma urea N compared with other treatments. Daily N intake linearly decreased ( < 0.01) with decreasing dietary CP and RDP levels, whereas the intake of RUP and fecal N excretion (g/d) did not change. Apparent digestibility of nutrients, ruminal pH, and NH-N concentration were not affected with decreasing dietary CP and RDP levels. Apparent N efficiency increased, and RDP N intake and predicted urine N output decreased with decreased concentration of dietary CP and RDP in the diets ( < 0.01). Blood metabolites were not affected by treatments. In conclusion, to improve the efficiency of N utilization by early-lactation dairy cows, 9.3% RDP in rations provides adequate protein to optimize milk production while minimizing N excretion in urine when the amounts of lysine and methionine and the lysine to methionine ratio are balanced with sufficient dietary RUP.

Phytogenic Administration and Reduction of Dietary Energy and Protein Levels Affects Growth Performance, Nutrient Digestibility and Antioxidant Status of Broilers

The aim of this study was to investigate the effect of reduced dietary energy (ME) and protein (CP) levels along with administration of a phytogenic feed additive (PFA) based on oregano, anise and citrus essential oils, on broiler growth performance, nutrient digestibility, meat and blood biochemical parameters and total antioxidant capacity (TAC).Depending on dietary ME and CP level down regulation compared to a corn-soybean meal basal diet A used as positive control, three diet types [A, B(=A-3%) and C(=A-6%)] were implemented. Depending on the inclusion or not of PFA at 125 mg/kg diet, 450 1-d old, male Cobb broilers were randomly allocated in six treatments according to a 3×2 factorial arrangement with 5 replicates of 15 broilers; A: diets formulated optimally to meet broiler nutrient requirements for maximizing protein content of meat for starter, grower and finisher growth periods; APh: A+PFA; B: suboptimal in ME and CP levels by 3%; BPh: B+PFA; C: suboptimal in ME and CP levels by 6%; CPh: C+PFA.Feed conversion ratio (FCR) was improved in birds fed diet A compared to diet C during the grower period (PD=0.021) and overall (PD=0.010). Phytogenic supplementation resulted in higher (PD×Ph=0.020) total tract apparent digestibility of fat in birds fed diet C compared to diet A. Birds fed diet A had higher (PD=0.001) plasma cholesterol, compared to birds fed diet C. In addition, birds fed diets A and B had higher (PD=0.002) breast protein content compared to C. Overall, PFA inclusion reduced cholesterol (PPh=0.002) and increased plasma TAC (PPh<0.001). Moreover, PFA increased breast (PPh=0.001) and thigh (PPh=0.01) TAC. In conclusion, a reduction in dietary ME and CP levels, adversely affected the FCR, whereas PFA supplementation tended (PPh=0.089) to compensate these effects. Moreover, the addition of PFA reduced plasma cholesterol and improved plasma and meat TAC.

Improvement in Nutritional Quality of Shrimp Meal with Autoclave and Chemical Treatments: an in vitro Study.

The present study was conducted to improve the nutritional quality of shrimp meal (SM) comprising of heads with hulls of black tiger shrimp (Penaeus monodon) waste by autoclaving and chemical treatments. The sun-dried SM was divided into 5 treatment groups, such as 1) control (untreated), 2) autoclaved (autoclaved at 121°C for 10 min), 3) NaOH (treated with 3% NaOH), 4) HCl (treated with 3% HCl) and 5) formic acid (treated with 3% formic acid) groups. After treatment, they were ground to pass through 1.0 mm mesh screen and then used for analyses of chemical composition and in vitro dry matter (DM) and CP digestibilities. Data were subjected to one-way ANOVA and differences among treatment means (P<0.05) were distinguished with Tukey's test. There were no significant difference in chemical composition and in vitro DM and CP digestibilities between control and autoclaved groups, except ether extract level (P<0.05), suggesting that autoclaving affected the nutritional quality of SM little. NaOH group exhibited significantly decreased CP level and in vitro DM digestibility, increased crude ash (CA) level and unchanged in vitro CP digestibility, comparing with control group. These results suggest that NaOH treatment affected the nutritional quality of SM adversely. HCl and formic acids groups showed significantly increased CP level and in vitro digestibilities of DM and CP, and decreased CA level, showing that acid treatment can improve nutritional quality of SM: formic acid treatment may be more effective because of the greater values in CP level and digestibilities and decreased crude fibre level which was not observed in HCl group (P<0.05). The results obtained here suggest acid, especially formic acid, treatment is promising to improve the nutritional quality of SM but autoclaving and NaOH treatments.

Performance of Quality Protein Maize Under Different Planting Windows

A field experiment was conducted at Forage Research Block, ICAR-NDRI, Karnal during post rainy season of 2014 and 2015 to study the performance of quality protein maize (QPM) cultivars under different planting windows. The treatments consisted of four sowing times viz., Aug. 15, Sept. 5, Sept. 25 and Oct. 15 in main plots and five maize cultivars HQPM-1, HQPM-4, HM-10, African tall and J-1006 in subplots in a split plot design. August 15 sowing recorded the maximum plant height, leaf length, leaf width, number of leaves per plant, green fodder yield (53.49 and 56.17 t/ha) and DM yield (11.39 and 12.03 t/ha) during 2014 and 2015, respectively. The performance of Aug. 15 sown maize in post monsoon season was at par with Sept. 5 sowing, however, further delay in sowing led to a significant (P<0.05) reduction in growth parameters and fodder yield. October 15 sown crop showed reduction (P<0.05) in these growth parameters. The maximum yield was obtained in African tall and the cultivars J-1006, HQPM-1 and HQPM-4 were at par with African tall while HM-10 gave the lowest yield. The levels of CP and NDF were influenced (P<0.05) by planting windows and CP contain increased and NDF decreased with delay in sowing, however, no significant variation in quality parameters was found among the QPM and normal fodder maize cultivars.

Transmembrane delivery of anticancer drugs through self-assembly of cyclic peptide nanotubes.

Breaking the natural barriers of cell membranes achieves fast entry of therapeutics, which leads to enhanced efficacy and helps overcome multiple drug resistance. Herein, transmembrane delivery of a series of small molecule anticancer drugs was achieved by the construction of artificial transmembrane nanochannels formed by self-assembly of cyclic peptide (cyclo[Gln-(d-Leu-Trp)4-d-Leu], CP) nanotubes (CPNTs) in the lipid bilayers. Our in vitro study in liposomes indicated that the transport of molecules with sizes smaller than 1.0 nm, which is the internal diameter of the CPNTs, could be significantly enhanced by CPNTs in a size-selective and dose-dependent manner. Facilitated uptake of 5-fluorouracil (5-FU) was also confirmed in the BEL7402 cell line. On the contrary, CPs could facilitate neither the transport across liposomal membranes nor the uptake by cell lines of cytarabine, a counterevidence drug with a size of 1.1 nm. CPs had a very weak anticancer efficacy, but could significantly reduce the IC50 of 5-FU in BEL7402, HeLa and S180 cell lines. Analysis by a q test revealed that a combination of 5-FU and CP had a synergistic effect in BEL7402 at all CP levels, in S180 at CP levels higher than 64 μg mL(-1), but not in HeLa, where an additive effect was observed. Temporarily, intratumoral injection is believed to be the best way for CP administration. In vivo imaging using (125)I radio-labelled CP confirmed that CPNPTs were completely localized in the tumor tissues, and translocation to other tissues was negligible. In vivo anticancer efficacy was studied in the grafted S180 solid tumor model in mice, and the results indicated that tumor growth was greatly inhibited by the combinatory use of 5-FU and CP, and a synergistic effect was observed at CP doses of 0.25 mg per kg bw. It is concluded that facilitated transmembrane delivery of anticancer drugs with sizes smaller than 1.0 nm was achieved, and the synergistic anticancer effect was confirmed both in cell lines and in vivo through the combinatory use of 5-FU and CP.

Probability-Based Seismic Performance Evaluation for Buildings

Recent developments in earthquake engineering indicate that probabilistic seismic risk analysis (PSRA) is becoming increasingly useful for the evaluation of structural per-formance in accordance with building codes. In recent years, the field of seismic resis-tance design has been undergoing a critical shift in focus from strength to performance. However, current earthquake resistant design procedures do not relate building performance to probability. A lack of sufficient empirical data has highlighted gaps in this research. This study integrated results from the analysis of structural fragility and seismic hazard in Taiwan to perform PSRA to examine the effectiveness of building code in mitigating the risks associated with earthquakes. Factors taken into account included the effect of construction materials, building height, and building age. The results of this study show that the probability of exceeding damage associated with the CP level in buildings of light steel, pre-cast concrete, and masonry, exceeds 2%. These buildings fail to meet the performance objectives outlined in FEMA-273.

Effects of low-protein diets supplemented with indispensable amino acids on growth performance, intestinal morphology and immunological parameters in 13 to 35 kg pigs

The objective of this study was to determine if a moderate or high reduction of dietary CP, supplemented with indispensable amino acids (IAA), would affect growth, intestinal morphology and immunological parameters of pigs. A total of 40 barrows (initial BW=13.50±0.50 kg, 45±2 day of age) were used in a completely randomized block design, and allocated to four dietary treatments containing CP levels at 20.00%, 17.16%, 15.30% and 13.90%, respectively. Industrial AA were added to meet the IAA requirements of pigs. After 4-week feeding, blood and tissue samples were obtained from pigs. The results showed that reducing dietary CP level decreased average daily gain, plasma urea nitrogen concentration and relative organ weights of liver and pancreas (P<0.01), and increased feed conversion ratio (P<0.01). Pigs fed the 13.90% CP diet had significantly lower growth performance than that of pigs fed higher CP at 20.00%, 17.16% or 15.30%. Moreover, reducing dietary CP level decreased villous height in duodenum (P<0.01) and crypt depth in duodenum, jejunum and ileum (P<0.01). The reduction in the dietary CP level increased plasma concentrations of methionine, alanine (P<0.01) and lysine (P<0.05), and decreased arginine (P<0.05). Intriguingly, reducing dietary CP level from 20.00% to 13.90% resulted in a significant decrease in plasma concentration of IgG (P<0.05), percentage of CD3+T cells of the peripheral blood (P<0.01), also down-regulated the mRNA abundance of innate immunity-related genes on toll-like receptor 4, myeloid differentiation factor 88 (P<0.01) and nuclear factor kappa B (P<0.05) in the ileum. These results indicate that reducing dietary CP level from 20.00% to 15.30%, supplemented with IAA, had no significant effect on growth performance and had a limited effect on immunological parameters. However, a further reduction of dietary CP level up to 13.90% would lead to poor growth performance and organ development, associated with the modifications of intestinal morphology and immune function.

Effects of ractopamine hydrochloride and dietary protein content on performance, carcass traits and meat quality of Nellore bulls

Ractopamine hydrochloride (RH) alters protein metabolism and improves growth performance in Bos taurus cattle with high carcass fat. Our objective was to evaluate the effects of RH, dietary CP and RH×CP interaction on performance, blood metabolites, carcass characteristics and meat quality of young Nellore bulls. A total of 48 bulls were randomly assigned to four treatments in a 2×2 factorial arrangement. The factors were two levels of dietary CP (100% and 120% of metabolizable protein requirement, defined as CP100 and CP120, respectively), and two levels of RH (0 and 300 mg/animal·per day). Treated animal received RH for the final 35 days before slaughter. Animals were weighed at the beginning of the feedlot period (day 63), at the beginning of ractopamine supplementation (day 0), after 18 days of supplementation (day 18) and before slaughter (day 34). Animals were slaughtered and hot carcass weights recorded. After chilling, carcass data was collected and longissimus samples were obtained for determination of meat quality. The 9–11th rib section was removed for carcass composition analysis. Supplementation with RH increased ADG independently of dietary CP. There was a RH×CP interaction on dry matter intake (DMI), where RH reduced DMI at CP120, with no effect at CP100. Ractopamine improved feed efficiency, without RH×CP interaction. Ractopamine had no effect on plasma creatinine and urea concentration. Greater dietary CP tended to increase blood urea, and there was a RH×CP interaction for plasma total protein. Ractopamine supplementation increased plasma total protein at CP120, and had no effect at CP100. Ractopamine also decreased plasma glucose concentration at CP100, but had no effect at CP120. Ractopamine increased alkaline phosphatase activity at CP120 and had no effect at CP100. There was a tendency for RH to increase longissimus muscle area, independently of dietary CP. Ractopamine did not alter fat thickness; however, fat thickness was reduced by greater CP in the diet. Supplementation with RH decreased meat shear force, but only at day 0 of aging, having no effect after 7, 14 or 21 days. Greater dietary protein increased meat shear force after 0 and 7 days of aging, with no effect after 14 or 21 days. These results demonstrate for the first time the efficacy of ractopamine supplementation to improve gain and feed efficiency of intact Bos indicus males, with relatively low carcass fat content. Ractopamine effects were not further improved by increasing dietary protein content above requirements.

Manipulation of dietary methionine+cysteine and threonine in broilers significantly decreases environmental nitrogen excretion

The intensification of livestock have increased the emission of pollutants to the environment, leading to a growing interest in seeking strategies that minimise these emissions. Studies have shown that it is possible to manipulate diets by reducing CP levels and thus reducing nitrogen (N) excretion, without compromising performance. However, there is no knowledge of any study that has focused on reducing N excretion and relating this reduction to individual amino acids. This study investigated the effect of dietary methionine+cysteine (MC) and threonine (THR), the two most limiting amino acids for broiler production, on nitrogen excretion (NE) and nitrogen deposition (ND) and determined the efficiency of utilisation of both amino acids for protein deposition. Six trials were conducted to measure the NE and ND in broiler chickens during three rearing phases in response to dietary amino acid. The efficiency of utilisation of the amino acids was calculated by linear regression of body protein deposition and the amino acid intake. Despite the differences between sexes and phases, the efficiency of utilisation was the same, being 0.60 and 0.59 for MC and THR, respectively. The rate of NE behaved exponentially, increasing with amino acid intake, and can exceed 50% of N intake, being higher than ND. On average, for a reduction in intake of each unit of MC or THR (mg) there is a reduction of 0.5% of NE. Although this reduction seems low, considering that it corresponds to changes in one amino acid only, the impact on a large scale would be significant. Knowledge of how animals respond to NE and ND/protein deposition according to amino acid dietary content may represent new efforts towards reducing the impact on environment.

Influence of Protein Supply on Threonine Efficiency and Threonine Catabolism in Hepatic Mitochondria of Chicks and Rats

Abstract This research investigated the relationship between efficiency of threonine (Thr) utilization and Thr oxidation in hepatic mitochondria in chicks and rats fed with graded levels (5.5-33.0% CP for chicks, 6-24% CP for rats) of protein. Calculation of efficiency of Thr utilization was based on N-balance data and an exponential N-utilization model, and Thr dehydrogenase (TDG) activity was determined. According to the results, no significant effect on TDG activity was observed in the liver of chicks who received diets containing from 5.5 up to 16.5% CP. However, significantly elevated TDG activities were observed, despite limited supply of Thr in protein, with diets containing from 22.0 up to 33.0% CP. At the levels of CP content from 5.5 up to 27.5%, no significant change in efficiencies of Thr utilization was observed. However, a significant decrease in efficiency was observed with diets containing from 27.5 to 33.0% CP. In chicks, the relationship between oxidation of Thr and Thr efficiency was observed with graded CP levels. In addition, elevated TDG activities in rat liver were observed with diets containing from 6.0 to 12.0% CP. At the levels of CP content from 6.0 up to 24.0%, no significant effect on efficiency of Thr utilization was observed in rats. In addition, no relationship was observed between Thr oxidation and efficiency of Thr utilization with graded CP levels in rats. Taken together, reactions for TDG appear to be animal species-dependent.

A simple estimation of ideal profile of essential amino acids and metabolizable energy for growing Japanese quail.

An experiment was conducted to determine apparent metabolizable energy (AME) and amino acid requirements of growing Japanese quail based on ideal protein concept using artificial neural network and desirability function (D-ANN). Seven-day-old quail chicks were assigned to nine experimental diets based on central composite design (CCD) containing five levels of AME (2809-3091kcal/kg) and CP (19-24.8% of diet). The ratio of lysine (Lys) to CP was set at 0.053 among all treatments, and remaining essential amino acids (EAA) were adjusted to Lys. The experimental data of CCD were fitted to D-ANN model to compute the optimal values for independent variables. The optimal values of inputs including AME, CP, digestible Lys (dLys), methionine (dMet), total sulphur amino acids (dTSAA), threonine (dThr), tryptophan (dTrp), isoleucine (dIle), valine (dVal) and arginine (dArg) for maximizing gain and minimizing feed conversion ratio were estimated at 2865kcal/kg, 25, 1.32, 0.55, 0.88, 0.84, 0.20, 0.75, 1.04 and 1.45% of diet, respectively, with D (desirability function)=0.94. The corresponding optimal amounts of amino acids based on total amino acids were 1.42, 0.59, 0.95, 0.90, 0.22, 0.81, 1.12 and 1.56% of diet respectively. The ideal pattern of essential amino acids to Lys was as follows: dMet: dLys=0.42, dTSAA: dLys=0.67, dThr: dLys=0.64, dTrp: dLys=0.15, dIle: dLys=0.57, dVal: dLys=0.79 and dArg: dLys=1.09. The results of this study showed that amino acid requirements of modern quails might be higher than those reported by NRC.

Technical Note: Collection and preparation techniques change nutrient composition of masticate collected from esophageally fistulated cattle.

Two experiments determined effects of collection and preparation techniques on nutrient composition of masticate samples from esophageally fistulated cattle. In Exp. 1, 12 esophageally fistulated cattle were maintained on 2 precollection diets, high CP (24% CP; = 6) or low CP (7.7% CP; = 6), for 8 d. On d 9, the esophageal plug was removed, screen bottom bags were attached, and each cow was offered fresh grass. Immediately after fresh grass sample collection was complete, dry grass (hay) was offered and a sample was collected. Blood samples were collected and analyzed for serum urea nitrogen concentration. Masticate samples of both fresh and dry grass were divided and each was either squeezed by hand until no more saliva could be removed or remained unsqueezed. In Exp. 2, 10 esophageally fistulated cattle were fitted with either screen ( = 5) or solid ( = 5) bottom collection bags after removal of the esophageal plug and presented grass hay, fresh grass, alfalfa hay, or fresh alfalfa. In Exp. 1, the precollection diet did not affect ( = 0.49) CP content of masticate even though serum urea nitrogen tended to be greater ( = 0.08) for high- vs. low-CP precollection diets. Forage harvest type offered (fresh vs. hay) interacted ( = 0.01) with preparation technique (squeezed vs. unsqueezed) for CP, where CP decreased in squeezed fresh samples ( < 0.001) but not in squeezed grass hay samples ( = 0.98). In Exp. 2, ingestion greatly increased levels of ash ( < 0.001). Crude protein was greater ( < 0.004) before ingestion for all samples except grass hay ( = 0.43). Levels of NDF were similar before and after ingestion ( > 0.15) for all samples except fresh alfalfa, which was greater after ingestion ( = 0.002). Ingestion status did not affect in vitro OM disappearance (IVOMD; > 0.34) except for grass hay, which was greater after ingestion ( < 0.001). Bag type (screen vs. solid) did not affect ash and NDF ( > 0.31), except for fresh alfalfa, which were greater ( < 0.03) for solid bottom bags. Bag type did not affect alfalfa CP ( = 0.71) but did affect grass CP, which was lower ( = 0.02) for solid bottom bags. Bag type did not affect IVOMD ( > 0.33). More ( = 0.01) fresh forage than hay was recovered through the esophageal opening. Previous diet did not impact masticate samples but squeezing impacted CP levels of high-quality forage and therefore should not be performed. Nutrient values should be reported on an OM basis.

Down-regulation of a signaling mediator in association with lowered plasma arachidonic acid levels in individuals with autism spectrum disorders

Previous studies have indicated that the altered composition of polyunsaturated fatty acids (PUFAs) might contribute to the pathophysiology of autism spectrum disorder (ASD). We examined the relationship between the plasma fatty acid levels, expressed as μg/ml, and the plasma levels of biomarkers of AA-related signaling mediators, such as ceruloplasmin, transferrin and superoxide dismutase, and assessed the behavioral symptoms of 30 individuals with ASD (mean age, 13.6 ± 4.3 years old) compared with 20 age- and gender-matched normal controls (mean age, 13.2 ± 5.4 years old) using Aberrant Behavior Checklists (ABC). The plasma levels of EPA and the plasma ratios of EPA/AA were significantly higher, while the plasma levels of AA and metabolites, such as 5,8,11,14-eicosatetraenoic acid, adrenic acid, and ceruloplasmin (Cp), were significantly lower in the 30 individuals with ASD compared with the 20 normal controls. The ABC scores were significantly increased in the ASD group compared with those of the control group. Thus, the results of the present study revealed that reduced plasma levels of AA and metabolites in association with high plasma EPA/AA ratios might down-regulate AA-related signaling mediators, such as Cp. Subsequently, reduced plasma Cp levels might reduce the protective capacity for brain damage, resulting in the pathophysiology underlying the behavioral symptoms in individuals with ASD. These findings suggest that reduced plasma AA levels may downregulate Cp.

The Features of Copper Metabolism in the Rat Liver during Development.

Strong interest in copper homeostasis is due to the fact that copper is simultaneously a catalytic co-factor of the vital enzymes, a participant in signaling, and a toxic agent provoking oxidative stress. In mammals, during development copper metabolism is conformed to two types. In embryonic type copper metabolism (ETCM), newborns accumulate copper to high level in the liver because its excretion via bile is blocked; and serum copper concentration is low because ceruloplasmin (the main copper-containing protein of plasma) gene expression is repressed. In the late weaning, the ETCM switches to the adult type copper metabolism (ATCM), which is manifested by the unlocking of copper excretion and the induction of ceruloplasmin gene activity. The considerable progress has been made in the understanding of the molecular basis of copper metabolic turnover in the ATCM, but many aspects of the copper homeostasis in the ETCM remain unclear. The aim of this study was to investigate the copper metabolism during transition from the ETCM (up to 12-days-old) to the ATCM in the rats. It was shown that in the liver, copper was accumulated in the nuclei during the first 5 days of life, and then it was re-located to the mitochondria. In parallel with the mitochondria, copper bulk bound with cytosolic metallothionein was increased. All compartments of the liver cells rapidly lost most of their copper on the 13th day of life. In newborns, serum copper concentration was low, and its major fraction was associated with holo-Cp, however, a small portion of copper was bound to extracellular metallothionein and a substance that was slowly eluted during gel-filtration. In adults, serum copper concentration increased by about a factor of 3, while metallothionein-bound copper level decreased by a factor of 2. During development, the expression level of Cp, Sod1, Cox4i1, Atp7b, Ctr1, Ctr2, Cox17, and Ccs genes was significantly increased, and metallothionein was decreased. Atp7a gene’s activity was fully repressed. The copper routes in newborns are discussed.

Effect of treating alfalfa silage with pistachio by-products extract on Saanen dairy goats performance and microbial nitrogen synthesis.

A lactation experiment was conducted to determine the influence of addition of pistachio by-products extract (PBE) to alfalfa silage (AS) on performance, rumen fermentation, milk yield and composition, and microbial nitrogen synthesis. Eight multiparous dairy goats (1.8±0.25kg of milk yield) were used in a replicated 4×4 Latin square design with a 2×2 factorial arrangement of treatments to compare two types of AS (supplemented with or without PBE) with two levels of dietary crude protein (14% vs. 16% CP). Dietary treatments were (i) AS with 14% CP of DM diet without PBE (14%CP-PBE), (ii) AS with 14% CP of DM diet with PBE (14%CP+PBE), (iii) AS with 16% CP of DM diet without PBE (16%CP-PBE) and (iv) AS with 16% CP of DM diet with PBE (16%CP+PBE). PBE was sprayed on fresh alfalfa at a ratio of 500ml/kg alfalfa DM to get the final concentration of 1% tannin as tannic acid equivalent on DM basis. Intake of CP was greater (p<0.01) in goats fed 16% CP diets than those fed 14% CP diets, regardless of PBE supplementation. Supplementation of PBE tended to decrease (p=0.09) rumen NH3 -N concentration regardless of the level of CP in the diet. Supplementation of PBE tended (p=0.09) to decrease total purine derivatives regardless of the level of CP in the diet with no significant change in microbial nitrogen supply. Efficiency of microbial nitrogen synthesis (EMNS) had a tendency (p=0.07) to decrease in PBE supplemented diets. There was also a tendency (p=0.10) for more EMNS in 14% CP fed goats than those fed 16% CP diets. Therefore, AS supplemented with PBE may lead to less concentration of ruminal NH3 -N because of decreased degradation of CP by rumen micro-organisms in response to pistachio by-products tannins.

Effect of energy and protein levels on performance, egg quality, and nutrient digestibility of laying pigeons

A total of 3,240 female Taisheng pigeons at 40 wk age were fed 9 diets containing 3 ME levels (2,630, 2,770, and 2,940 kcal/kg) and 3 CP levels (14.0, 15.0, and 16.0%) in a factorial arrangement. These diets were fed to investigate the effects of ME and CP on performance, egg quality, and nutrient digestibility. Female pigeons were housed under the same managerial conditions and randomly assigned into 9 treatments (6 replicates of 60 birds each). Two female–female paired pigeons housed in one cage were under a 16L:8D lighting cycle. Feed in pellet form and water were provided for ad libitum consumption. The study lasted 12 wk. As dietary ME level increased from 2,630 to 2,940 kcal/kg, BW, egg production, and apparent DM, crude fat (CF), and phosphorus (i.e., P) digestibilities increased (P < 0.05), feed intake decreased (P < 0.05), and feed conversion efficiency increased (P < 0.05). Increasing the level of dietary protein from 14 to 16% resulted in an increased (P < 0.05) BW, shell percentage, length of the major axis, and DM digestibility. Therefore, dietary ME had a greater influence on the performance of Taisheng laying pigeons than did dietary protein.

Effects of protein sources and levels in antibiotic-free diets on diarrhea, intestinal morphology, and expression of tight junctions in weaned piglets

This study examined effects of dietary protein sources and levels on intestinal health of 21 to 35 d-old weaned piglets fed antibiotics-free diets. A total of 150 weaned piglets (21 d of age) were allotted to 5 dietary treatment groups. Diets were formulated, based on corn-soybean meal, with different protein sources (fish meal and soy protein concentrate) to provide different dietary CP levels. Piglets within 5 dietary treatments were fed diets as follows, respectively: 1) control diet of 17% CP (control); 2) 19% CP diets formulated with more soy protein concentrate (SPC19); 3) fish meal (FM19); 4) 23.7% CP diets formulated with more soy protein concentrate (SPC23); 5) fish meal (FM23). The results showed that piglets from control group had higher ADG and lower incidence of diarrhea compared with those of other groups (P < 0.05). The incidence of diarrhea of piglets in FM19 group was lower than those from SPC23 group and FM23 group (P < 0.05). With the higher CP levels, villous height and villous height to crypt depth ratio of piglets in the duodenum and jejunum were decreased (P < 0.05), but crypt depth was increased (P < 0.05). Comparing control group and other groups, we found the expression of inflammatory cytokines interleukin-1β (IL-1β) and interferon-γ (IFN-γ) were increased (P < 0.05) in the jejunum and colon of piglets, as did cystic fibrosis transmembrane conductance regulators (CFTR) in the distal colon. The relative transcript abundance of Zonula occludens-1 (ZO-1) in the jejunum, and occludin in the jejunum and ileum of piglets fed 23.7% CP diets were reduced compared with those fed control diet (P < 0.05). In conclusion, the 17% CP diet without in-feed antibiotics helped improve growth performance and relief of diarrhea of 21 to 35 d-old weaned piglets. Dietary CP level, rather than its source (either fish meal or soy protein concentrate), has more significant impacts on the growth performance and intestinal health of 21 to 35 d-old weaned piglets when fed antibiotics-free diets.

Utilization of Different Corn Fractions by Broilers

This study was conducted to evaluate the nutritional values of fractions of damaged corn. One hundred and eighty 22-d-old Cobb 500 male broilers were distributed in batteries according to a completely randomized design with six treatments of six replicates each. The treatments consisted of diets containing five corn fractions, classified as sound, fermented, insect-damaged, mold-damaged, or reference corn. The test diets consisted of 60% of reference diet + 40% of each corn fraction. Only the reference corn fraction included all the fractions at different proportions (0.8% fermented, 0.05% insect-damaged, 3.3% mold-damaged, and 95.85% sound grains). The method of total excreta collection was used to determine AMEn values and metabolizability coefficients of dry matter (MDM), crude protein (MCP), ether extract (MEE), and gross energy (MGE) of the reference corn and its fractions. The density values of the corn fractions were used to calculate the correlations among the evaluated parameters. The evaluated corn fractions presented different compositions values. The insect-damaged and mold-damaged grains presented higher CP level, lower density, and MDM and MCP coefficients compared with the other fractions. However, calculated AMEn values were not significantly different (p>0.05) among corn fractions. A low correlation between density and AMEn content (r 0.8) were calculated. Although the evaluated corn fractions presented different nutritional values, there were no marked differences in their utilization by broilers.