Identifying cattle with superior growth feed efficiency through their natural 15N abundance and plasma urea concentration: a meta-analysis.

The objective of this study was to test two candidate biomarkers of feed efficiency in growing cattle. A database was built using performance data from 13 trials conducted with growing heifers, steers and young bulls and testing 34 dietary treatments. The database included 769 individual records for animal performance and laboratory data for N isotopic discrimination measured in plasma or muscle (Δ15Nanimal-diet; n = 749) and plasma urea concentration (n = 659). Feed conversion efficiency (FCE) and residual feed intake (RFI) criteria were calculated for a duration ranging between 56 and 259 d, depending on the trial. For FCE prediction, mixed models included the random effects of study, diet within-study and pen within-study (i.e. contemporary group; CG) allowing these effects to be progressively excluded from the relationship. For RFI prediction, simple linear regressions were tested with the CG effect removed from biomarker values before analysis. Better models were obtained with Δ15Nanimal-diet compared to plasma urea concentration, irrespective of using mean or individual values and regardless of the feed efficiency criterion. Prediction error (0.027 kg/kg) from mixed-effect models using mean FCE and Δ15Nanimal-diet values would allow discrimination of 2 dietary treatments or production conditions in terms of FCE if they differ by more than 0.10 kg/kg. The Δ15Nanimal-diet values showed a negative and significant (P<0.001) relationship with FCE at the individual level and results highlighted that it is possible to significantly discriminate two animals randomly selected from the same CG if they differ by at least 0.06 kg/kg FCE. In addition, the top 20% highest and lowest animals within-CG in terms of RFI and FCE (extreme animals) showed significant (P<0.001) differences in Δ15Nanimal-diet values, while only extreme FCE animals could be discriminated when using plasma urea concentrations (P=0.002). No gain in feed efficiency prediction was observed when combining candidate biomarkers. However for FCE, when average daily gain data was combined with Δ15Nanimal-diet, the prediction at the individual level was strengthened compared to using only single predictors. Our findings confirm that Δ15Nanimal-diet may be useful to form groups of animals for precision feeding. Further studies are warranted, however, to evaluate the usefulness of this promising biomarker for genetic selection.

Evaluation of peptidylarginine deiminase 4 and PADI4 polymorphisms in sepsis-induced acute kidney injury

SUMMARY BACKGROUND: The aim of this study is to evaluate the peptidylarginine deiminase 4 (PAD 4) concentration and PADI4 polymorphisms as predictors of acute kidney injury (AKI) development, the need for renal replacement therapy (RRT), and mortality in patients with septic shock. METHODS: We included all individuals aged ≥ 18 years, with a diagnosis of septic shock at ICU admission. Blood samples were taken within the first 24 hours of the patient's admission to determine serum PAD4 concentration and its PADI4 polymorphism (rs11203367) and (rs874881). Patients were monitored during their ICU stay and the development of SAKI was evaluated. Among the patients in whom SAKI developed, mortality and the need for RRT were also evaluated. RESULTS: There were 99 patients, 51.5% of whom developed SAKI and of these, 21.5% needed RRT and 80% died in the ICU. There was no difference between PAD4 concentration (p = 0.116) and its polymorphisms rs11203367 (p = 0.910) and rs874881 (p = 0.769) in patients in whom SAKI did or did not develop. However, PAD4 had a positive correlation with plasma urea concentration (r = 0.269 and p = 0.007) and creatinine (r = 0.284 and p = 0.004). The PAD4 concentration and PADI4 polymorphisms were also not associated with RRT and with mortality in patients with SAKI. CONCLUSION: PAD4 concentration and its polymorphisms were not associated with SAKI development, the need for RRT, or mortality in patients with septic shock. However, PAD4 concentrations were associated with creatinine and urea levels in these patients.

Time-Dependent miRNA Profile during Septic Acute Kidney Injury in Mice

(1) Background: Lipopolysaccharide (LPS)-induced systemic inflammation is associated with septic acute kidney injury (AKI). We investigated the time-dependent miRNA expression changes in the kidney caused by LPS. (2) Methods: Male outbred NMRI mice were injected with LPS and sacrificed at 1.5 and 6 h (40 mg/kg i.p., early phase, EP) or at 24 and 48 h (10 mg/kg i.p., late phase, LP). The miRNA profile was established using miRCURY LNA™ microarray and confirmed with qPCR. Total renal proteome was analyzed by LC-MS/MS (ProteomeXchange: PXD014664). (3) Results: Septic AKI was confirmed by increases in plasma urea concentration and in renal TNF-α and IL-6 mRNA expression. Most miRNAs were altered at 6 and 24 h and declined by 48 h. In EP miR-762 was newly identified and validated and was the most elevated miRNA. The predicted target of miR-762, Ras related GTPase 1B (Sar1b) was downregulated. In LP miR-21a-5p was the most influenced miRNA followed by miR-451a, miR-144-3p, and miR-146a-5p. Among the potential protein targets of the most influenced miRNAs, only aquaporin-1, a target of miR-144-3p was downregulated at 24 h. (4) Conclusion: Besides already known miRNAs, septic AKI upregulated miR-762, which may regulate GTP signaling, and miR-144-3p and downregulated its target, aquaporin-1.

Effectiveness and optimum level of protected methionine in fattening pig diets

Background: Methionine (Met) requirements have not been clearly established for fattening pigs due to their metabolic interrelationships and its bioavailability for protein synthesis. Objective: To determine the optimum level of regular crystalline or protected Met in pig diets from nursery to finishing. Methods: A total of 48 crossbred pigs (11.74±1.72 kg of initial body weight) were used. The treatments consisted of adding four levels (0.00, 0.05, 0.10, 0.15% in addition to dietary content) and two types of Met (regular and protected) to pig diets. Results: Nursery, Finishing I, and II pigs fed protected Met increased daily feed intake (DFI; p≤0.10). Protected Met raised daily weight gain (DWG) in nursery pigs and increased backfat thickness (BT) in nursery and grower pigs (p≤0.10). In Finishing I pigs, protected Met increased DWG and improved carcass characteristics (p≤0.10). In nursery and grower pigs, an extra 0.15% Met decreased feed:gain ratio (FGR; p≤0.10). In grower and Finishing II pigs fed extra 0.05% Met improved DWG and extra 0.10% Met reduced plasma urea concentration (p≤0.10). Conclusions: Feeding protected Met in pig diets increases DWG, DFI and BT. Increasing 0.05-0.15% Met level improves FGR, DWG, potentially reducing nitrogen excretion to the environment.

Time-Dependent miRNA Profile in the Mouse Kidney during LPS Preconditioning

Background: Pre-treatment with lipopolysaccharide (LPS) protected the kidney against a later lethal ischemia. To reveal the mechanisms of renal cross-tolerance and septic acute kidney injury we investigated the effects of LPS on miRNA expression in the kidney. Methods: Male NMRI mice were injected with 40 and 10 mg/kg LPS ip. and sacrificed at 1.5 and 6 hours (early preconditioning, EP) and at 24 and 48 hours (late preconditioning, LP). The miRNA profile was established using miRCURY LNA&trade; microarray and confirmed with qPCR. Results: Plasma urea concentration peaked at 24 hours after LPS and decreased thereafter. Renal TNF-&alpha; and IL-6 mRNA were extremely elevated at all time-points. miRNome changes were mild at 1.5 hours, most miRNAs were altered at 6 and 24 hours and declined by 48 hours. Not all miRNAs could be assayed or validated by qPCR. In EP miR-762 was newly identified and validated and was the most elevated miRNA with both methods. In LP miR-21a-5p was the most influenced miRNA followed by miR-451a, miR-144-3p and miR-146a-5p. MiR-21a-3p increased significantly in both EP and LP. Conclusion: miR-762 might attenuate the LPS-induced immune response during EP and the miR-144/451 cluster is involved in LPS-induced renal preconditioning.

Evaluation of peptidylarginine deiminase 4 concentration and PADI4 polymorphisms in sepsis-induced acute kidney injury

Background: The influence of PAD4 concentration and its polymorphisms in SAKI development are poorly evaluated. Thus, the aim of this study is to evaluate the PAD 4 concentration and PADI4 polymorphisms, as predictors of AKI development, need for renal replacement therapy (RRT), and mortality in patients with septic shock. Methods: We included all individuals aged ≥ 18 years, with the diagnosis of septic shock at ICU admission. Blood samples were taken within the first 24 hours of the patient’s admission to determine serum PAD4 concentration and its polymorphism PADI4 (rs11203367) and (rs874881). Patients were followed during their ICU stay and the development of SAKI was evaluated. Among the patients in whom SAKI developed, mortality and need for RRT were also evaluated. Results: 99 patients were included in the analysis. SAKI developed in approximately 51.5% of patients during the ICU stay; of these, 21.5% required RRT and 80% died. There was no difference between PAD4 concentration (p = 0.116) and its polymorphisms rs11203367 (p = 0.910) and rs874881 (p = 0.769) in patients in whom SAKI did or did not develop. However, PAD4 had a positive correlation with plasma urea concentration (r = 0.269 and p = 0.007) and creatinine (r = 0.284 and p = 0.004). The PAD4 concentration and PADI4 polymorphisms were also not associated with RRT and with mortality in patients with SAKI. Conclusion: PAD4 concentration and its polymorphisms were not associated with SAKI development, the need for RRT, or mortality in patients with septic shock. However, PAD4 concentrations were associated with creatinine and urea levels in these patients.

Relationships of both urine nitrogen output and plasma urea concentration with rumen protein balance in lactating goats

The updated INRA system incorporates the notion of rumen protein balance (RPB, g CP/kg DM) in an attempt to better fit feed evaluation, animal requirements and responses to diets. RPB is the difference between crude protein intake and entrance at the duodenum (excluding NH3) which is not very easy to measure in vivo. The aim of this study was to test the strength of the relationships between dietary RPB values obtained from the diet composition and criteria easier to measure, such as N urinary outputs or plasma urea concentration, both at a treatment level and at an individual level in a large dataset obtained from lactating goats fed different types of diets. RPB was a better predictor of urinary N output and plasma urea concentration than was the former French system for protein digestible in the intestine. Within experiments, RPB was highly and positively correlated with urinary nitrogen outputs and plasma urea concentration. RPB can be used to estimate the urinary N output in lactating dairy goats, but this study also showed that some of the residual variance was due to variability among animals.

Effects ofdl-2-hydroxy-4-methylthiobutyrate on the first-pass intestinal metabolism of dietary methionine and its extra-intestinal availability

The present study was conducted in a one-factorial arrangement to determine the effects ofdl-2-hydroxy-4-methylthiobutyrate (dl-HMTB) on the first-pass intestinal metabolism of dietary methionine and its extra-intestinal availability. Barrows (n6; aged 35 d; weight 8·6 kg), implanted with arterial, portal, mesenteric and gastric catheters, were fed a diet containingdl-methionine (dl-MET) ordl-HMTB once hourly and infused intramesenterically with 1 %p-aminohippurate and intragastrically with [1-13C]methionine at 7·0 μmol/kg body weight per h. Arterial and portal blood samples were taken at hourly intervals until 6 h of tracer infusion and pigs was then killed for collection of muscle, intestine, liver and kidney samples. The net portal appearance of methionine, expressed as the fraction of ingested directly availablel-methionine, was higher (P < 0·05) in thedl-HMTB than in thedl-MET diet, and there was no difference (P = 0·26) in the fractional portal balance of [1-13C]methionine between the diets. [1-13C]methionine enrichment (tracer:tracee ratio; mol/100 mol amino acid) in the jejunum, arterial and portal plasma, liver, kidney and muscle was also not different (P>0·05) between the groups. Over the 6 h period after the start of feeding, the average concentration of citrulline both in the arterial and portal plasma was higher (P < 0·05) in thedl-HMTB than in thedl-MET group, and arterial plasma ornithine and taurine concentration was also higher (P < 0·05) in thedl-HMTB than in thedl-MET group. However, plasma urea concentration both in the arterial and portal vein was lower (P < 0·05) in thedl-HMTB than in thedl-MET group. These results suggested that the potential difference in the first-pass use of methionine by the intestine between thedl-HMTB anddl-MET diets might affect intestinal and systemic metabolism of other amino acids, which may provide new important insights into nutritional efficiency of different methionine sources.

Ractopamine for finishing barrows fed restricted or ad libitum diets: performance and nitrogen balance

Supplementation of 5 ppm of ractopamine, associated or not to feed restriction in diets with a high total lysine content (1.04%) was evaluated on performance and nitrogen balance. In experiment 1, 60 hybrid castrated male swine (76.2 ± 2.3 kg) were housed in pairs according to a randomized complete block design in a factorial treatment arrangement (2 ×2 + 1) with or without ractopamine supplementation, two forms of feeding, ad libitum and feed restriction with 1.04% lysine, and an additional treatment (control), with ad libitum feed without ractopamine with 0.8% lysine, amounting to five treatments and six replications. The final live weight, daily weight gain, daily feed intake and feed conversion for 28 days were evaluated. There were improvements in supplementation with ractopamine for final live weight, daily weight gain and feed conversion. The ad libitum feeding improved both final live weight and daily weight gain compared with ractopamine. Compared with the control, there was a decrease in feed conversion with ractopamine supplementation and improvement for final weight (FW) in the treatment with the ractopamine and ad libitum feed. In experiment 2, 30 hybrid castrated male swine (74.1 ± 2.5 kg) were housed in metabolism cages and fed the same experimental treatments to evaluate the percentages of absorbed nitrogen (Nabs), retained nitrogen (Nret), nitrogen retained from the absorbed nitrogen (Nret/Nabs) and the plasma urea concentration at 14 and 28 days. At 14 days, there was an increase in the Nret/Nabs and plasma urea concentration with ractopamine supplementation. Compared with the control, there was a decrease in the plasma urea concentration for feed restriction with ractopamine. At 28 days, there was an increase in the Nret/Nabs with ractopamine supplementation. Thus supplementation with 5 ppm ractopamine improved the performance and efficiency of swine nitrogen use. Feed restriction interfered negatively in weight gain, but it improved the efficiency of the nitrogen use of barrows.