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Objective: The protein equivalent of total nitrogen appearance (PNA) formula, based on the urea nitrogen appearance (UNA), is popularly used by stable continuous ambulatory peritoneal dialysis (CAPD) patients to estimate dietary daily protein intake (DPI). However, we found that the estimated DPI was higher than that directly evaluated from the dietary records of most of our CAPD patients. Therefore, in the present study, we tried to determine possible bias in PNA estimation by UNA with a nitrogen balance study of our CAPD patients., Methods: Thirty-one CAPD patients with stable clinical conditions were included. Their 3-day dietary records were reviewed by a dedicated dietitian to calculate their energy, protein, and nitrogen intake (NI). The nitrogen removal (NR) from urine and dialysate was measured by the Kjeldahl technique. Then, we calculated the proportion of urea nitrogen appearance (UNA) in total nitrogen appearance (TNA) and analyzed the possible factors that could affect this proportion., Results: Among these patients, 17 males and 14 females, the mean age was 64.19 ± 12.42, and the dialysate drainage volume was 6700 (2540) ml/day. The percentage of UNA in TNA was 63.22 ± 6.66%. Compared with the other classic nitrogen balance studies in the CAPD population, the protein nitrogen and other nonurea nitrogen losses in this study were all lower. Based on these 31 nitrogen balance studies, we proposed a pair of new equations to estimate PNA by UNA. (1) PNA = 9.3 + 7.73 UNA; (2) PNA = PNPNA + TPL = 6.7 + 7.28 UNA + TPL., Conclusion: Our study suggested that the PNA formula generated from previous European studies overestimated DPI in our CAPD patients.

Osteoarthritis is a common multifactorial chronic disease that occurs in articular cartilage, subchondral bone, and periarticular tissue. The pathogenesis of OA is still unclear. To investigate the differences in serum metabolites between OA and the control group, liquid chromatography/mass spectrometry (LC/MS)-based metabolomics was used. To reveal the pathogenesis of OA, 12 SD male rats were randomly divided into control and OA groups using collagenase to induce OA for modeling, and serum was collected 7 days after modeling for testing. The OA group was distinguished from the control group by principal component analysis and orthogonal partial least squares-discriminant analysis, and six biomarkers were finally identified. These biomarkers were metabolized through tryptophan metabolism, glutamate metabolism, nitrogen metabolism, spermidine metabolism, and fatty acid metabolism pathways. The study identified metabolites that may be altered in OA, suggesting a role in OA through relevant metabolic pathways. Metabolomics, as an important tool for studying disease mechanisms, provides useful information for studying the metabolic mechanisms of OA.

Nitrogen balance is the difference between nitrogen excreted as urea and nitrogen ingested, mainly in proteins. Increased circulating concentrations of amino acids (AA) in the bloodstream are usually associated with proportional increases in the production and excretion of urea. Previously, we reported results from a randomized, controlled, single-dose, crossover trial in healthy adult volunteers (n = 30) (Trial Registration: ISRCTN11016729), in which a Test product (prolonged-release AA mixture formulated with Physiomimic Technology™ (PT™)) significantly slowed down the release and reduced the peak plasma concentrations of essential AAs compared with a free AA mixture (Reference product) while maintaining essential AA bioavailability. Here, we report an assessment of the nitrogen balance from the same study. The amount of nitrogen contained in plasma AAs, levels of blood urea nitrogen (BUN) ( p < 0.0001) and changes in BUN ( p < 0.0001) were smaller after the Test product compared with the Reference product. These findings suggest that the production of urea in proportion to systemic AA availability was significantly smaller after the administration of the Test product compared with the Reference product and that the test product conferred the increased utilization of AAs for protein synthesis and reduced their oxidation and conversion to urea. In the clinical setting, it is possible that the effects of PT™ observed on the disposition of free AAs in this study may translate to health benefits in terms of physiological body composition and growth if used for the treatment of subjects with phenylketonuria (PKU). Further investigation in patients with PKU is warranted.

Due to global aging, frailty and sarcopenia are increasing. Sarcopenia is defined as loss of volume and strength of skeletal muscle in elderlies, while frailty involves multiple domains of aging-related dysfunction, impaired cognition, hypomobility, and decreased social activity. However, little is known about the metabolic basis of sarcopenia, either shared with or discrete from frailty. Here we analyzed comprehensive metabolomic data of human blood in relation to sarcopenia, previously collected from 19 elderly participants in our frailty study. Among 131 metabolites, we identified 22 sarcopenia markers, distinct from 15 frailty markers, mainly including antioxidants, although sarcopenia overlaps clinically with physical frailty. Notably, 21 metabolites that decline in sarcopenia or low SMI are uremic compounds that increase in kidney dysfunction. These comprise TCA cycle, urea cycle, nitrogen, and methylated metabolites. Sarcopenia markers imply a close link between muscle and kidney function, while frailty markers define a state vulnerable to oxidative stress.

Background and Aims: Combining energy and protein targets during the acute phase of critical illness is challenging. Energy should be provided progressively to reach targets while avoiding overfeeding and ensuring sufficient protein provision. This prospective observational study evaluated the feasibility of achieving protein targets guided by 24-h urinary nitrogen excretion while avoiding overfeeding when administering a high protein-to-energy ratio enteral nutrition (EN) formula., Methods: Critically ill adult mechanically ventilated patients with an APACHE II score > 15, SOFA > 4 and without gastrointestinal dysfunction received EN with hypocaloric content for 7 days. Protein need was determined by 24-h urinary nitrogen excretion, up to 1.2 g/kg (Group A, N = 10) or up to 1.5 g/kg (Group B, N = 22). Variables assessed included nitrogen intake, excretion, balance; resting energy expenditure (REE); phase angle (PhA); gastrointestinal tolerance of EN., Results: Demographic characteristics of groups were similar. Protein target was achieved using urinary nitrogen excretion measurements. Nitrogen balance worsened in Group A but improved in Group B. Daily protein and calorie intake and balance were significantly increased in Group B compared to Group A. REE was correlated to PhA measurements. Gastric tolerance of EN was good., Conclusions: Achieving the protein target using urinary nitrogen loss up to 1.5 g/kg/day was feasible in this hypercatabolic population. Reaching a higher protein and calorie target did not induce higher nitrogen excretion and was associated with improved nitrogen balance and a better energy intake without overfeeding. PhA appears to be related to REE and may reflect metabolism level, suggestive of a new phenotype for nutritional status. Trial registration 0795-18-RMC.

Dinitrogen (N 2 ) has been increasingly connected to suicidal deaths. The analysis of N 2 in post-mortem cases still represents a major challenge in forensic toxicology and circumstantial data has so far played a major role for the determination of the cause of death. In this paper, after presenting a review of cases of N 2 intoxication described in forensic literature, we report the application of two approaches in order to quantify an excess of N 2 in post-mortem whole blood collected from a case of suicide by nitrogen inhalation. N 2 analyses were performed by GC-MS on the suicidal case and on controls taken from 10 autopsy cases with similar PMI (5 traumatic deaths and 5 deaths by asphyxia). The percentage of N 2 was estimated by building a five-point N 2 peak area calibration curve (0, 15.6 %, 62.4 % 78.1 %, 100 %) and through an external QC, assessing linearity, accuracy and precision, LLOQ, specificity and stability of N 2 in the sample vial. Percentage of N 2 of the case was significantly higher than the post-mortem controls (p<0.05). The N 2 /O 2 ratio of the case and controls was also calculated as an additional indicator, and was significantly higher in the case (p<0.05). The strengths and the limitation of both methods are reported in the paper. Toxicological confirmation for N 2 are rarely performed when the cause of death is evident, probably due to the lack of validated methods and the complexity of the interpretation of N 2 concentration in biological fluids. The presented methods can be rapidly and profitably applied with instrumentation normally available in forensic laboratories., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The goal of nutrition support is to provide the substrates required to match the bioenergetic needs of the patient and promote the net synthesis of macromolecules required for the preservation of lean mass, organ function, and immunity. Contemporary observational studies have exposed the pervasive undernutrition of critically ill patients and its association with adverse clinical outcomes. The intuitive hypothesis is that optimization of nutrition delivery should improve ICU clinical outcomes. It is therefore surprising that multiple large randomized controlled trials have failed to demonstrate the clinical benefit of restoring or maximizing nutrient intake. This may be in part due to the absence of biological markers that identify patients who are most likely to benefit from nutrition interventions and that monitor the effects of nutrition support. Here, we discuss the need for practical risk stratification tools in critical care nutrition, a proposed rationale for targeted biomarker development, and potential approaches that can be adopted for biomarker identification and validation in the field.

We worked out the growth and dissolution rates of an arterial gas embolism (AGE), to illustrate the evolution over time of its size and composition, and the time required for its total dissolution. We did this for a variety of breathing gases including air, pure oxygen, Nitrox and Heliox (each over a range of oxygen mole fractions), in order to assess how the breathing gas influenced the evolution of the AGE. The calculations were done by numerically integrating the underlying rate equations for explicitly multi-component AGEs, that contained a minimum of three (water, carbon dioxide and oxygen) and a maximum of five components (water, carbon dioxide, oxygen, nitrogen and helium). The rate equations were straight-forward extensions of those for a one-component gas bubble. They were derived by using the Young-Laplace equation and Dalton's law for the pressure in the AGE, the Laplace equation for the dissolved solute concentration gradients in solution, Henry's law for gas solubilities, and Fick's law for diffusion rates across the AGE/arterial blood interface. We found that the 1-component approximation, under which the contents of the AGE are approximated by its dominant component, greatly overestimates the dissolution rate and underestimates the total dissolution time of an AGE. This is because the 1-component approximation manifestly precludes equilibration between the AGE and arterial blood of the inspired volatile solutes (O 2 , N 2 , He) in arterial blood. Our calculations uncovered an important practical result, namely that the administration of Heliox, as an adjunct to recompression therapy for treating a suspected N 2 -rich AGE must be done with care. While Helium is useful for preventing nitrogen narcosis which can arise in aggressive recompression therapy wherein the N 2 partial pressure can be quite high (e.g.∼5 atm), it also temporarily expands the AGE, beyond the expansion arising from the use of Oxygen-rich Nitrox. For less aggressive recompression therapy wherein nitrogen narcosis is not a significant concern, Oxygen-rich Nitrox is to be preferred, both because it does not temporarily expand the AGE as much as Heliox, and because it is much cheaper and more conservation-minded., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The aim of this experimental study was to investigate the protective effect of Ganoderma lucidum capsules against colistin nephrotoxicity. The study animals were separated into four groups: control, colistin (9 mg/kg), colistin-G. lucidum 50 mg/kg, and colistin-G. lucidum 100 mg/kg. In the colistin group, serum blood urea nitrogen and creatinine values were found to be higher than those of the other groups (p < 0.001). The malondialdehyde, catalase, total oxidative stress, oxidative stress index, and oxidized glutathione values in serum and kidney tissue samples were determined to be higher in the colistin group than in the other groups (p < 0.001). The total antioxidative stress, superoxide dismutase, glutathione peroxidase, and glutathione values measured in the serum and kidney tissue samples were determined to be lower in the colistin group (p < 0.001). Oxidative stress is responsible for tubule damage in colistin nephrotoxicity, and when G. lucidum is used together with colistin, renal damage is reduced.

Background: The nitrogen isotope ratio (NIR) is a promising index of traditional food intake for an Alaska Native (Yup'ik) population, which can be measured in blood and hair. However, the NIR has not been calibrated to high-quality measures of Yup'ik traditional food intake., Objectives: Our primary objective was to examine associations between intakes of Yup'ik traditional food groups, including fish, marine mammals, birds, land mammals, berries, greens, and total traditional foods, and the NIR. In an exploratory analysis, we also examined whether NIR analyzed sequentially along hair could reflect dietary seasonality., Methods: We recruited 68 participants from 2 Yup'ik communities in the Yukon Kuskokwim region of Southwest Alaska (49% female, aged 14-79 y). Participants completed 4 unscheduled 24-h food recalls over the period peak of RBC and hair synthesis preceding a specimen collection visit. The NIR was measured in RBCs ( n = 68), a proximal hair section (n = 58), and sequential segments of hair from individuals in the upper 2 quartiles of traditional food intake having hair >6 cm in length, plus 2 low subsistence participants for reference (n = 18). Diet-biomarker associations were assessed using Pearson's correlation and linear regression., Results: Intakes of fish, marine mammals, berries, and greens were significantly associated with the NIR. The strongest dietary association was with total traditional food intake (R2 = 0.62), which indicated that each 1‰ increase in the RBC NIR corresponded to 8% of energy from traditional foods. Hair NIR appeared to fluctuate seasonally in some individuals, peaking in the summertime., Conclusions: Findings support the use of the RBC and hair NIR to assess total traditional food intake in a Yup'ik population. Analyses of sequential hair NIR provided evidence of seasonality in traditional food intake, although seasonal variations were modest relative to interindividual variation., (Copyright © American Society for Nutrition 2019.)

To avoid boar taint before slaughtering, late castration by immunisation against gonadotrophin releasing hormone or immunocastration has been developed. The current study aimed at determining whether differences in feed efficiency between castrated male (CM), immune castrated (IM) and entire male pigs (EM) can be explained by differences in nutrient plasma profiles after a meal. In this study, 24 male pigs ( n = 8/type) were enrolled between 14 to 19 weeks of age. Entire and IM pigs ate less and were more feed efficient than CM pigs ( p < 0.05). The postprandial plasma profiles of glucose, insulin, urea and amino acids (AA) were determined before (d -6), just after (d 8) and well after (d 16) the decrease in testicular hormones in IM pigs. For each test day, pigs were fasted overnight and subsequently fed a small meal (400 g). On d -6, postprandial profiles of plasma glucose of IM pigs did not differ from the two other types of pigs. On d 8, EM pigs had a greater average plasma glucose concentration than IM and CM pigs ( p < 0.05) but the profiles did not differ. On d 16, the differences between profiles of glucose suggest a lower clearance of glucose in EM compared with IM and CM pigs. Plasma insulin did not significantly differ between the three types. Plasma urea profiles did not differ between CM, EM and IC pigs on d -6 whereas CM pigs showed higher plasma urea concentrations than EM and IM thereafter ( p < 0.01). Among AA, Lys plasma concentrations were greater in CM than in EM and IM pigs on d -6, d 8 and d 16 ( p < 0.05), whereas on d 16 plasma Hypro concentrations were lower in CM than in EM and IM pigs ( p < 0.05). The finding that plasma glucose profiles were modified by immunocastration much faster and earlier than urea and AA profiles, suggest that the decrease in testicular hormones impacted energy metabolism more rapidly than protein metabolism.

The aim of this study was to evaluate the associated effects of ambient temperature and inflammation caused by repeated administration of Escherichia coli lipopolysaccharide (LPS) on insulin, energy, and AA metabolism. Twenty-eight pigs were assigned to one of the two thermal conditions: thermoneutral (24 °C) or high ambient temperature (30 °C). The experimental period lasted 17 d, which was divided into a 7-d period without LPS (days -7 to -1), and a subsequent 10-d LPS period (days 1 to 10) in which pigs were administered 5 repeated injections of LPS at 2-d intervals. Postprandial profiles of plasma insulin and nutrients were evaluated through serial blood samples taken on days -4 (P0), 4 (P1), and 8 (P2). Before the LPS-challenge (P0), postprandial concentrations of glucose, lactate, Gln, Ile, Leu, Phe, Tyr, and Val were greater in pigs kept at 24 °C than at 30 °C (P < 0.05). In contrast, Arg, Asp, Gly, His, and Met postprandial concentrations at P0 were lower at 24 °C than at 30 °C (P < 0.05). At both 24 and 30 °C conditions, pigs had greater postprandial concentrations of insulin (P < 0.01) and lower concentrations of NEFA (P < 0.01) and α-amino nitrogen (P < 0.05) at P1 and P2 than at P0. Compared with P0, postprandial concentrations of glucose were greater (P < 0.05) at P1 in pigs kept at 24 °C, and at P1 and P2 in pigs kept at 30 °C. At both ambient temperatures, pigs had lower (P < 0.05) postprandial concentrations of Ala, Gly, His, Ile, Leu, Pro, Ser, Thr, Trp, and Val at P1 and P2 than at P0. Arginine postprandial concentration at P1 was lower than at P0 in pigs kept at 24 °C (P < 0.05), whereas no difference was observed in pigs at 30 °C. Relative to P0, Gln and Tyr concentrations were lower at P1 and P2 in pigs kept at 24 °C (P < 0.01), whereas lower Gln concentration was observed only at P2 (P < 0.01) and lower Tyr only at P1 (P < 0.01) in pigs kept at 30 °C. Our study shows a hyperglycemic and hyperinsulinemic state in LPS-challenged pigs and a greater magnitude of this response in pigs kept at 30 °C. Furthermore, LPS caused important changes in BCAA, His, Thr, and Trp profiles, suggesting the role these AA in supporting the inflammatory response. Finally, our results suggest that LPS-induced effects on postprandial profiles of specific AA (Arg, Gln, Phe, and Tyr) may be modulated by ambient temperature., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To study the differences in the levels of nitrogen metabolites, such as ammonia and nitric oxide and the correlations existing among them in both red blood cells (RBCs) and serum, as well as the possible differences by gender in healthy subjects and patients with type 2 Diabetes Mellitus (DM)., Design and Methods: This cross-sectional study included 80 patients diagnosed with type 2 DM (40 female and 40 male patients) and their corresponding controls paired by gender (40 female and 40 male). We separated serum and RBC and determined metabolites mainly through colorimetric and spectrophotometric assays. We evaluated changes in the levels of the main catabolic by-products of blood nitrogen metabolism, nitric oxide (NO), and malondialdehyde (MDA)., Results: Healthy female and male controls showed a differential distribution of blood metabolites involved in NO metabolism and arginine metabolism for the ornithine and urea formation. Patients with DM had increased ammonia, citrulline, urea, uric acid, and ornithine, mainly in the RBCs, whereas the level of arginine was significantly lower in men with type 2 DM. These findings were associated with hyperglycemia, glycosylated hemoglobin (Hb A1C), and levels of RBC's MDA. Furthermore, most of the DM-induced alterations in nitrogen-related metabolites appear to be associated with a difference in the RBC capacity for the release of these metabolites, thereby causing an abrogation of the gender-related differential management of nitrogen metabolites in healthy subjects., Conclusions: We found evidence of a putative role of RBC as an extra-hepatic mechanism for controlling serum levels of nitrogen-related metabolites, which differs according to gender in healthy subjects. Type 2 DM promotes higher ammonia, citrulline, and MDA blood levels, which culminate in a loss of the differential management of nitrogen-related metabolites seen in healthy women and men., Competing Interests: The authors have declared that no competing interests exist.

Objective: The aim of the study was to determine the lacrimal fluid (LF) contents of glucose, urea nitrogen, and creatinine in cats., Animal Studied: A total of 96 cats were included in the study., Procedure: Venous blood and LF samples were collected. For LF sampling, three small polyurethane sponges were placed in the ventral fornix of both eyes. Both LF and plasma concentrations of glucose, urea nitrogen, and creatinine were quantitatively analyzed and compared., Result: Glucose (n = 40) and urea nitrogen concentrations (n = 42) measured in LF from both eyes highly correlated. While there was a very strong correlation (ρ = 0.97) between urea nitrogen concentrations in blood plasma and the corresponding tear levels (with the median LF urea nitrogen being 109% of that measured in plasma), the LF glucose concentrations were significantly lower than the corresponding plasma concentrations (with only 13% of the blood glucose concentration detected in the LF). The creatinine concentrations in tears were much lower than those in plasma, and LF creatinine was detectable in only 12/48 cats (25%). Hence, a comparison of the LF creatinine concentrations between both eyes or with the corresponding plasma creatinine concentration was not possible., Conclusion: Measurement of LF urea nitrogen concentrations in cats appears to be reliable and might have potential clinical utility. Measurement of LF glucose concentrations is less reliable but may still be useful in some cats. Creatinine is not reliably detected in the LF in cats. Further studies determining clinical utility of LF metabolites in cats and other companion animals are warranted., (© 2018 American College of Veterinary Ophthalmologists.)

INTRODUCTION: The frequency of long-duration, high-altitude missions with fighter aircraft is increasing, which may increase the incidence of decompression sickness (DCS). The aim of the present study was to compare decompression stress during simulated sustained high-altitude flying vs. high-altitude flying interrupted by periods of moderate or marked cabin pressure increase. METHODS: The level of venous gas emboli (VGE) was assessed from cardiac ultrasound images using the 5-degree Eftedal-Brubakk scale. Nitrogen washout/uptake was measured using a closed-circuit rebreather. Eight men were investigated in three conditions: one 80-min continuous exposure to a simulated cabin altitude of A) 24,000 ft, or four 20-min exposures to 24,000 ft interspersed by three 20-min intervals at B) 20,000 ft or C) 900 ft. RESULTS: A and B induced marked and persistent VGE, with peak bubble scores of [median (range)]: A: 2.5 (1-3); B: 3.5 (2-4). Peak VGE score was less in C [1.0 (1-2), P < 0.01]. Condition A exhibited an initially high and exponentially decaying rate of nitrogen washout. In C the washout rate was similar in each period at 24,000 ft, and the nitrogen uptake rate was similar during each 900-ft exposure. B exhibited nitrogen washout during each period at 24,000 ft and the initial period at 20,000 ft, but on average no washout or uptake during the last period at 20,000 ft. DISCUSSION: Intermittent reductions of cabin altitude from 24,000 to 20,000 ft do not appear to alleviate the DCS risk, presumably because the pressure increase is not sufficient to eliminate VGE. The nitrogen washout/uptake rate did not reflect DCS risk in the present exposures. Ånell R, Grönkvist M, Eiken O, Gennser M. Nitrogen washout and venous gas emboli during sustained vs. discontinuous high-altitude exposures . Aerosp Med Hum Perform. 2019; 90(6):524-530.

Introduction: Glycerol phenylbutyrate (GPB) is approved in the US and EU for the chronic management of patients ≥2 months of age with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. GPB is a pre-prodrug, hydrolyzed by lipases to phenylbutyric acid (PBA) that upon absorption is beta-oxidized to the active nitrogen scavenger phenylacetic acid (PAA), which is conjugated to glutamine (PAGN) and excreted as urinary PAGN (UPAGN). Pharmacokinetics (PK) of GPB were examined to see if hydrolysis is impaired in very young patients who may lack lipase activity., Methods: Patients 2 months to <2 years of age with UCDs from two open label studies (n = 17, median age 10 months) predominantly on stable doses of nitrogen scavengers (n = 14) were switched to GPB. Primary assessments included traditional plasma PK analyses of PBA, PAA, and PAGN, using noncompartmental methods with WinNonlin™. UPAGN was collected periodically throughout the study up to 12 months., Results: PBA, PAA and PAGN rapidly appeared in plasma after GPB dosing, demonstrating evidence of GPB cleavage with subsequent PBA absorption. Median concentrations of PBA, PAA and PAGN did not increase over time and were similar to or lower than the values observed in older UCD patients. The median PAA/PAGN ratio was well below one over time, demonstrating that conjugation of PAA with glutamine to form PAGN did not reach saturation. Covariate analyses indicated that age did not influence the PK parameters, with body surface area (BSA) being the most significant covariate, reinforcing current BSA based dosing recommendations as seen in older patients., Conclusion: These observations demonstrate that UCD patients aged 2 months to <2 years have sufficient lipase activity to adequately convert the pre-prodrug GPB to PBA. PBA is then converted to its active moiety (PAA) providing successful nitrogen scavenging even in very young children., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Exercise ventilation/perfusion matching in continuous-flow left ventricular assist device recipients (LVAD) has not been studied systematically. Twenty-five LVAD and two groups of 15 reduced ejection fraction chronic heart failure (HFrEF) patients with peak VO2 matched to that of LVAD (HFrEF-matched) and ≥14 ml/kg/min (HFrEF≥14), respectively, underwent cardiopulmonary exercise testing with arterial blood gas analysis, echocardiogram and venous blood sampling for renal function evaluation. Arterial-end-tidal PCO2 difference (P(a-ET)CO2) and physiological dead space-tidal volume ratio (VD/VT) were used as descriptors of alveolar and total wasted ventilation, respectively. Tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio (TAPSE/PASP) and blood urea nitrogen/creatinine ratio were calculated in all patients and used as surrogates of right ventriculo-arterial coupling and circulating effective volume, respectively. LVAD and HFrEF-matched showed no rest-to-peak change of P(a-ET)CO2 (4.5±2.4 vs. 4.3±2.2 mm Hg and 4.1±1.4 vs. 3.8±2.5 mm Hg, respectively, both p >0.40), whereas a decrease was observed in HFrEF≥14 (6.5±3.6 vs. 2.8±2.0 mm Hg, p <0.0001). Rest-to-peak changes of P(a-ET)CO2 correlated to those of VD/VT (r = 0.70, p <0.0001). Multiple regression indicated TAPSE/PASP and blood urea nitrogen/creatinine ratio as independent predictors of peak P(a-ET)CO2. LVAD exercise gas exchange is characterized by alveolar wasted ventilation, i.e. hypoperfusion of ventilated alveoli, similar to that of advanced HFrEF patients and related to surrogates of right ventriculo-arterial coupling and circulating effective volume., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Recent reports have shown that intraoperative infusions of glucose and amino acids exert anticatabolic effects. The appropriate dosages of these amino acids and glucose during general anesthesia remain unknown., Methods: Patients who underwent esophagectomy for thoracic esophageal cancer were infused with acetated Ringer's solution that contained glucose and amino acids (B1 group [10 patients]: glucose, 3 g/h; amino acids, 1.2 g/h; B2 group [12 patients]: glucose, 4.5 g/h; amino acids, 1.8 g/h) or did not contain glucose and amino acids (C group, 10 patients). The measured energy expenditure was measured by indirect calorimetry. Nitrogen balance was measured during the anesthesia, and the lengths of the hospital stay were recorded., Results: Resting energy expenditure (B1: 1230 ± 228; B2: 1317 ± 282; C: 1012 ± 153 kcal/h; B2 vs C, P < 0.05) and nitrogen balance (B1: -1.78 ± 0.78 g; B2: -0.85 ± 0.98 g; C: -2.94 ± 2.4 g; B2 vs C, P < 0.05) differed significantly between the B2 and C groups. The lengths of the hospital stay differed between the B2 and C groups (B1: 29 ± 15 d; B2: 18 ± 6 d; C: 37 ± 27 d; B2 vs C, P = 0.06)., Conclusions: The administration of amino acids and glucose increased measured energy expenditure, alleviated nitrogen balance, and may decrease the length of the hospital stay., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Urea cycle enzyme deficiency (UCED) patients with hyperammonemia are treated with sodium benzoate (SB) and sodium phenylacetate (SPA) to induce alternative pathways of nitrogen excretion. The suggested guidelines supporting their use in the management of hyperammonemia are primarily based on non-analytic studies such as case reports and case series. Canine congenital portosystemic shunting (CPSS) is a naturally occurring model for hyperammonemia. Here, we performed cross-over, randomized, placebo-controlled studies in healthy dogs to assess safety and pharmacokinetics of SB and SPA (phase I). As follow-up safety and efficacy of SB was evaluated in CPSS-dogs with hyperammonemia (phase II). Pharmacokinetics of SB and SPA were comparable to those reported in humans. Treatment with SB and SPA was safe and both nitrogen scavengers were converted into their respective metabolites hippuric acid and phenylacetylglutamine or phenylacetylglycine, with a preference for phenylacetylglycine. In CPSS-dogs, treatment with SB resulted in the same effect on plasma ammonia as the control treatment (i.e. saline infusion) suggesting that the decrease is a result of volume expansion and/or forced diuresis rather than increased production of nitrogenous waste. Consequentially, treatment of hyperammonemia justifies additional/placebo-controlled trials in human medicine.

Background: Chronic kidney disease (CKD) patients experience skeletal muscle wasting and decreased exercise endurance. Our previous study demonstrated that indoxyl sulfate (IS), a uremic toxin, accelerates skeletal muscle atrophy. The purpose of this study was to examine the issue of whether IS causes mitochondria dysfunction and IS-targeted intervention using AST-120, which inhibits IS accumulation, or mitochondria-targeted intervention using L-carnitine or teneligliptin, a dipeptidyl peptidase-4 inhibitor which retains mitochondria function and alleviates skeletal muscle atrophy and muscle endurance in chronic kidney disease mice., Methods: The in vitro effect of IS on mitochondrial status was evaluated using mouse myofibroblast cells (C2C12 cell). The mice were divided into sham or 5/6-nephrectomized (CKD) mice group. Chronic kidney disease mice were also randomly assigned to non-treatment group and AST-120, L-carnitine, or teneligliptin treatment groups., Results: In C2C12 cells, IS induced mitochondrial dysfunction by decreasing the expression of PGC-1α and inducing autophagy in addition to decreasing mitochondrial membrane potential. Co-incubation with an anti-oxidant, ascorbic acid, L-carnitine, or teneligliptine restored the values to their original state. In CKD mice, the body and skeletal muscle weights were decreased compared with sham mice. Compared with sham mice, the expression of interleukin-6 and atrophy-related factors such as myostatin and atrogin-1 was increased in the skeletal muscle of CKD mice, whereas muscular Akt phosphorylation was decreased. In addition, a reduced exercise capacity was observed for the CKD mice, which was accompanied by a decreased expression of muscular PCG-1α and increased muscular autophagy, as reflected by decreased mitochondria-rich type I fibres. An AST-120 treatment significantly restored these changes including skeletal muscle weight observed in CKD mice to the sham levels accompanied by a reduction in IS levels. An L-carnitine or teneligliptin treatment also restored them to the sham levels without changing IS level., Conclusions: Our results indicate that IS induces mitochondrial dysfunction in skeletal muscle cells and provides a potential therapeutic strategy such as IS-targeted and mitochondria-targeted interventions for treating CKD-induced muscle atrophy and decreased exercise endurance., (© 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

A seminal study recently demonstrated that bromide (Br-) has a critical function in the assembly of type IV collagen in basement membrane (BM), and suggested that Br- supplementation has therapeutic potential for BM diseases. Because salts of bromide (KBr and NaBr) have been used as antiepileptic drugs for several decades, repositioning of Br- for BM diseases is probable. However, the effects of Br- on glomerular basement membrane (GBM) disease such as Alport syndrome (AS) and its impact on the kidney are still unknown. In this study, we administered daily for 16 weeks 75 mg/kg or 250 mg/kg (within clinical dosage) NaBr or NaCl (control) via drinking water to 6-week-old AS mice (mouse model of X-linked AS). Treatment with 75 mg/kg NaBr had no effect on AS progression. Surprisingly, compared with 250 mg/kg NaCl, 250 mg/kg NaBr exacerbated the progressive proteinuria and increased the serum creatinine and blood urea nitrogen in AS mice. Histological analysis revealed that glomerular injury, renal inflammation and fibrosis were exacerbated in mice treated with 250 mg/kg NaBr compared with NaCl. The expressions of renal injury markers (Lcn2, Lysozyme), matrix metalloproteinase (Mmp-12), pro-inflammatory cytokines (Il-6, Il-8, Tnf-α, Il-1β) and pro-fibrotic genes (Tgf-β, Col1a1, α-Sma) were also exacerbated by 250 mg/kg NaBr treatment. Notably, the exacerbating effects of Br- were not observed in wild-type mice. These findings suggest that Br- supplementation needs to be carefully evaluated for real positive health benefits and for the absence of adverse side effects especially in GBM diseases such as AS.

Introduction: One of the most important issues in patients with chronic kidney disease is fluid retention and volume overload accompanied by retention of nitrogenous waste products and some electrolytes. Bowel fluid contains high levels of urea, creatinine, uric acid, and electrolytes, which make it a potential candidate for intestinal excretion of nitrogen wastes and electrolytes. Cross-linked polyelectrolyte (CLP) is a polymer that, given orally, absorbs excess fluid, electrolyte, and nitrogenous waste products., Materials and Methods: In an experimental study on 30 hemodialysis patients, the effect of CLP on adsorption of fluid, urea, creatinine, uric acid, sodium, and potassium were evaluated. For this purpose, 500 mL of effluent fluid of each patient were collected at the 1st hour of dialysis. The concentrations of the abovementioned products were measured by standard methods. Then the dialysate effluent samples were treated with 6 g of CLP and incubated for 4 hours at 37°C., Results: Up to 80% of effluent fluid water was adsorbed by CLP. There were significant reductions in urea, creatinine, uric acid, and sodium levels in the remaining effluent fluid (P < .001). In contrast, the amount of potassium increased in the effluent fluid., Conclusions: Using CLP in addition to functional medical super adsorbents can be a possible adequate substitute for conventional dialysis methods, especially hemodialysis.

In the management of patients with chronic kidney diseases (CKD), a low-protein diet usually refers to a diet with protein intake of 0.6 to 0.8 grams per kilogram of body weight per day (g/kg/day) and should include at least 50% high-biologic-value protein. It may be supplemented with essential acids or nitrogen-free ketoanalogues if <0.6 g/kg/d. Low-protein diet can reduce proteinuria especially in non-diabetic CKD patients. In hypoalbuminemic patients it may lead to an increase in serum albumin level. By lowering proteinuria, decreasing nitrogen waste products, ameliorating metabolic burden, mitigating oxidative stress and acidosis, and lowering phosphorus burden, a low-protein diet can help delay dialysis start in advanced CKD. Low-protein diet is safe, since most CKD patients can maintain nitrogen balance by mechanisms of decreasing amino acid oxidation and protein degradation in addition to increased utilization of amino acids for protein synthesis. We suggest a dietary protein intake below 1.0 g/kg/day when estimated glomerular filtration rate (eGFR) falls below 60 mL/min/1.73 m2 or when there is solitary kidney or proteinuria at any level of GFR. Protein intake should be reduced progressively based on severity and progression of CKD and patient's nutritional status with a target of 0.6-0.8 g/kg/d in most patients with eGFR <45 mL/min/1.73 m2. The risk of protein-energy wasting can be overcome by careful attention to quantity and quality of the ingested proteins, sufficient energy intake of 30-35 Kcal/kg/d, and use of dietary supplements. Long-term observations and individualized approaches are needed to further demonstrate the benefits and safety of low-protein diet.

Background: Artificial nutrition support is central to the care of critically ill patients and is primarily provided enterally (EN). There are circumstances when parenteral nutrition (PN) is considered necessary. We are uncertain how each of these approaches confer clinical benefits beyond simply providing calories. We sought to better understand how each of these techniques influence metabolism in critically ill patients using a broad-based metabolomics approach. Metabolic responses to EN and PN may differ in ways that could help us understand how to optimize use of these therapies., Methods: We prospectively enrolled subjects over 7 months in 2015 at an urban, Level I trauma center. Subjects were included before starting either EN or PN during their inpatient admission. Plasma samples were obtained between 1 and 12 hours before initiation of artificial nutrition, and 3 and 7 days later. All samples were analyzed with liquid chromatography/mass spectrometry-based metabolomics. Differences in metabolite concentrations were assessed via principal component analyses and multiple linear regression., Results: We enrolled 30 subjects. Among the critically ill subjects, 10 received EN and 10 received PN. In subjects receiving EN, amino acid and urea cycle metabolites (citrulline, p = 0.04; ornithine, p = 0.05) increased, as did ribonucleic acid metabolites (uridine, p = 0.04; cysteine, 0 = 0.05; oxypurinol, p = 0.04). Oxidative stress decreased over time (increased betaine, p = 0.05; decreased 4-pyridoxic acid, p = 0.04). In subjects receiving PN, amino acid concentrations increased over time (taurine, p = 0.04; phenylalanine, p = 0.05); omega 6 and omega 3 fatty acid concentrations decreased over time (p = 0.05 and 0.03, respectively)., Conclusion: EN was associated with amino acid repletion, urea cycle upregulation, restoration of antioxidants, and increasing ribonucleic acid synthesis. Parenteral nutrition was associated with increased amino acid concentrations, but did not influence protein metabolism or antioxidant repletion. This suggests that parenteral amino acids are used less effectively than those given enterally. The biomarkers reported in this study may be useful in guiding nutrition therapy for critically ill patients., Level of Evidence: Therapeutic study, level III; prognostic study, level II.

We examine both maximum likelihood and Bayesian approaches for estimating probabilistic decompression sickness model parameters. Maximum likelihood estimation treats parameters as fixed values and determines the best estimate through repeated trials, whereas the Bayesian approach treats parameters as random variables and determines the parameter probability distributions. We would ultimately like to know the probability that a parameter lies in a certain range rather than simply make statements about the repeatability of our estimator. Although both represent powerful methods of inference, for models with complex or multi-peaked likelihoods, maximum likelihood parameter estimates can prove more difficult to interpret than the estimates of the parameter distributions provided by the Bayesian approach. For models of decompression sickness, we show that while these two estimation methods are complementary, the credible intervals generated by the Bayesian approach are more naturally suited to quantifying uncertainty in the model parameters., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Residual kidney urea clearance in dialysis patients typically is calculated as the per minute excretion of urea nitrogen, obtained during the 24-48 hour collection period that usually ends just prior to a dialysis session, divided by the time-averaged serum water urea nitrogen concentration during the collection period. This concentration is difficult to estimate unless a formal kinetic modeling program is being used. We used a urea kinetic modeling program to derive an equation to estimate the time-averaged serum water concentration during urine collection periods of various lengths collected during various interdialytic intervals, for 3/week or 2/week dialysis schedules. The equation to predict time-averaged serum water urea nitrogen concentration during the collection period was a function of the ratio of the duration of the predialysis collection period to the duration of the interdialytic interval during which the collection was accomplished, as well as the urea reduction ratio and predialysis serum urea nitrogen concentration of the dialysis session immediately following the end of the collection period., (© 2016 Wiley Periodicals, Inc.)

Dehydroepiandrosterone (DHEA), the most abundant sex steroid, is primarily secreted by the adrenal gland and a precursor hormone used by athletes for performance enhancement. Whole-body vibration (WBV) is a well-known light-resistance exercise by automatic adaptations to rapid and repeated oscillations from a vibrating platform, which is also a simple and convenient exercise for older adults. However, the potential effects of DHEA supplementation combined with WBV training on to body composition, exercise performance, and hormone regulation are currently unclear. The objective of the study is to investigate the effects of DHEA supplementation combined with WBV training on body composition, exercise performance, and physical fatigue-related biochemical responses and testosterone content in young-adult C57BL/6 mice. In this study, male C57BL/6 mice were divided into four groups (n = 8 per group) for 6-weeks treatment: sedentary controls with vehicle (SC), DHEA supplementation (DHEA, 10.2 mg/kg), WBV training (WBV; 5.6 Hz, 2 mm, 0.13 g), and WBV training with DHEA supplementation (WBV+DHEA; WBV: 5.6 Hz, 2 mm, 0.13 g and DHEA: 10.2 mg/kg). Exercise performance was evaluated by forelimb grip strength and exhaustive swimming time, as well as changes in body composition and anti-fatigue levels of serum lactate, ammonia, glucose, creatine kinase (CK), and blood urea nitrogen (BUN) after a 15-min swimming exercise. In addition, the biochemical parameters and the testosterone content were measured at the end of the experiment. Six-week DHEA supplementation alone significantly increased mice body weight (BW), muscle weight, testosterone level, and glycogen contents (liver and muscle) when compared with SC group. DHEA supplementation alone had no negative impact on all tissue and biochemical profiles, but could not improve exercise performance. However, WBV+DHEA supplementation also significantly decreased BW, testosterone level and glycogen content of liver, as well as serum lactate and ammonia levels after the 15-min swimming exercise when compared with DHEA supplementation alone. Although DHEA supplementation alone had no beneficial effect in the exercise performance of mice, the BW, testosterone level and glycogen content significantly increased. On the other hand, WBV training combined with DHEA decreased the BW gain, testosterone level and glycogen content caused by DHEA supplementation. Therefore, WBV training could inhibit DHEA supplementation to synthesis the testosterone level or may decrease the DHEA supplement absorptive capacity in young-adult mice., Competing Interests: The authors declare no conflict of interest.

Sjögren's syndrome is an autoimmune disease that primarily affects exocrine glands. Renal involvement of Sjögren's syndrome may lead to tubulointerstitial disease, whereas secondary glomerulopathies such as anti-neutrophil cytoplasmic antibody (ANCA)-related pauci-immune crescentic glomerulonephritis are rarely observed. In addition, crescent glomerulonephritis that is simultaneously positive for both myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA has never been reported in Sjögren's syndrome. Here, we report a case of pauci-immune crescentic glomerulonephritis exhibiting positivity for both MPO- and PR3-ANCAs in a patient with primary Sjögren's syndrome. A 71-year-old female was hospitalized for cough, blood-tinged sputum, and dyspnea two weeks after diagnosis with Sjögren's syndrome. On admission, serum anti-nuclear antibody, anti-Ro/SS-A antibody, MPO-ANCA, and PR3-ANCA were all positive, and serum blood urea nitrogen and creatinine (Cr) levels were 42.7 and 2.9 mg/dL, respectively. On the seventh day of hospitalization, the patient's serum Cr level was 5.7 mg/dL, indicating rapidly progressive glomerulonephritis. Renal biopsy resulted in the diagnosis of ANCA-related pauci-immune crescentic glomerulonephritis, for which intravenous methylprednisolone (7 mg/kg/day) was administered for three consecutive days, followed by combination therapy with oral prednisolone (1 mg/kg/day) and intravenous cyclophosphamide (500 mg/m(2)). The patient was positive in the Schirmer's I test, and a salivary gland biopsy showed sialadenitis with lympho-plasmacytic infiltrations. On day 28 of hospitalization, the patient was discharged after amelioration of respiratory symptoms and azotemia. At 6 months after discharge, the patient continued to receive appropriate daily medications and was negative for both MPO- and PR3-ANCAs, with a slight elevation in serum Cr levels.

Purpose: To explore the effects of methane-rich saline (CH4 saline) on the capability of one-time exhaustive exercise in male SD rats., Methods: Thirty rats were equally divided into to three groups at random: control group (C), placebo group (P) and methane saline group (M). Rats in M group underwent intraperitoneal injection of CH4 saline, and the other two groups simultaneously underwent intraperitoneal injection of normal saline. Then, the exercise capability of rats was tested through one-time exhaustive treadmill exercise except C group. Exercise time and body weight were recorded before and after one-time exhaustive exercise. After exhaustive exercise, the blood and gastrocnemius samples were collected from all rats to detect biochemical parameters in different methods., Results: It was found that the treadmill running time was significantly longer in rats treated with CH4 saline. At the same time, CH4 saline reduced the elevation of LD and UN in blood caused by one-time exhaustive exercise. The low level of blood glucose induced by exhaustive exercise was also normalized by CH4 saline. Also CH4 saline lowered the level of CK in plasma. Furthermore, this research indicated that CH4 saline markedly increased the volume of T-AOC in plasma and alleviated the peak of TNF-α in both plasma and gastrocnemius. From H&E staining, CH4 saline effectively improved exercise-induced structural damage in gastrocnemius., Conclusions: CH4 saline could enhance exercise capacity in male SD rats through increase of glucose aerobic oxidation, improvement of metabolic clearance and decrease of exhaustive exercise-induced gastrocnemius injury.

This study investigated the effects of sheep genetics and feed intake on nitrogen isotopic fractionation (ΔN) and feed conversion efficiency (FCE; live weight gain/DMI), using a 2 × 2 factorial design, with 2 levels of genetic merit for growth (high vs. low) and 2 levels of feed intake (110 vs. 170% of ME for maintenance [MEm]). No effect of genetic merit was detected for live weight gain ( = 0.64), FCE ( = 0.46), plasma urea nitrogen ( = 0.52), plasma glucose ( = 0.78), and ΔN of wool ( = 0.45), blood ( = 0.09), and plasma ( = 0.51). Sheep receiving 170% of MEm had 175% higher live weight gain ( < 0.001) and 77% higher FCE ( < 0.001) than sheep receiving 110% of MEm. There was no difference among treatments at the beginning of the study for either blood or plasma ∆N, but the treatment groups started to diverge in blood and plasma ∆N at 21 and 7 d, respectively. Blood, plasma, and wool samples were enriched in N compared with feed. There was a higher blood, plasma, and wool ∆N for the low feed intake group than the high feed intake group ( < 0.001 in all cases). Across the 4 treatment groups, higher FCE in sheep was associated with lower ∆N for plasma, blood, and wool. Overall, the results are consistent with the potential of ∆N as a rapid, low-cost biomarker of FCE in sheep, despite there being no effects of genetic treatment on FCE and ∆N.

Background: Meat protein digestibility can be impaired because of indigestible protein aggregates that form during cooking. When the aggregates are subsequently fermented by the microbiota, they can generate potentially harmful compounds for the colonic mucosa., Objective: This study evaluated the quantity of bovine meat protein escaping digestion in the human small intestine and the metabolic fate of exogenous nitrogen, depending on cooking processes., Methods: Sixteen volunteers (5 women and 11 men; aged 28 ± 8 y) were equipped with a double lumen intestinal tube positioned at the ileal level. They received a test meal exclusively composed of 120 g of intrinsically (15)N-labeled bovine meat, cooked either at 55°C for 5 min (n = 8) or at 90°C for 30 min (n = 8). Ileal effluents and blood and urine samples were collected over an 8-h period after the meal ingestion, and (15)N enrichments were measured to assess the digestibility of meat proteins and the transfer of dietary nitrogen into the metabolic pools., Results: Proteins tended to be less digestible for the meat cooked at 90°C for 30 min than at 55°C for 5 min (90.1% ± 2.1% vs. 94.1% ± 0.7% of ingested N; P = 0.08). However, the particle number and size in ileal digesta did not differ between groups. The appearance of variable amounts of intact fibers was observed by microscopy. The kinetics of (15)N appearance in plasma proteins, amino acids, and urea were similar between groups. The amount of exogenous nitrogen lost through deamination did not differ between groups (21.2% ± 0.8% of ingested N)., Conclusions: Cooking bovine meat at a high temperature for a long time can moderately decrease protein digestibility compared with cooking at a lower temperature for a short time and does not affect postprandial exogenous protein metabolism in young adults. The study was registered at www.clinicaltrials.gov as NCT01685307., (© 2015 American Society for Nutrition.)

Aim: Diabetic nephropathy (DN) is the most frequent cause of end-stage renal disease. The activation of the renin-angiotensin system (RAS) and lipid disorders are major risk factors in progressive chronic kidney disease. Inhibition of the RAS is one of the most widely used therapies to treat chronic kidney disease. But its effect is not sufficient, and lowered hyperlipidemia is required. Most of medications for hypertension have effects only on the blood pressure in DN. This study is to evaluate the influence of irbesartan on blood lipid, kidney function, and the pathological change of kidney, liver, and adipose tissue., Methods: Six-week old db/db mice were randomly assigned to control group and irbesartan group. Mice in irbesartan group were fed 40 mg/kg irbesartan each day. Eight weeks later, blood lipid, kidney function, and the pathological change of kidney, liver, and adipose tissue were measured., Results: The results indicated that the blood lipid, uric acid, urea nitrogen, and creatinine of db/db mice increased significantly. There are obvious vacuolar degeneration and ballooned hepatocytes around the central vein of db/db mouse liver. Kidney biopsy found glomerular hypertrophy of glomerular, mesangial thickening, and vacuolar degeneration. Irbesartan can decrease the blood pressure, blood lipid, and kidney lipid. But it has no effects on blood glucose and liver lipid. It can improve the function and pathological change of kidney of db/db mice. But it has no effects on pathological change of adipose tissue and liver., Conclusions: Irbesartan can decrease blood lipid and protect the kidney of db/db mice, and is a good choice of treatment for diabetic nephropathy.

This study was set to investigate the effects of different nutrition supports in patients with cancer chemotherapy. 68 patients with cancer chemotherapy were selected from Enshi central hospital between January 2011 and June 2013, and divided into enteral nutrition support therapy group (44 cases) and parenteral group (24 cases) according to their nutritional support. Body mass index (BMI), nitrogen balance, serum albumin level, adverse reactions, chemotherapy compliance, and leukocyte count before and after chemotherapy were observed in the two groups of patients. There was no statistical difference among all the clinical factors in the two groups before treatment (P > 0.05). After two courses of chemotherapy, BMI, albumin (ALB), and nitrogen balance changed significantly (P < 0.05). In parenteral group, ALB and nitrogen balance reduced significantly (P < 0.05). Adverse reactions, chemotherapy compliance, and leukocyte drop after chemotherapy all showed significant changes (P < 0.05). Enteral nutrition support therapy can effectively improve malnutrition in patients with cancer chemotherapy, and can improve the immunity and chemotherapy compliance, reduce adverse reactions, which is the ideal nutrition support therapy.

Diabetic nephropathy (DN) is a severe microvascular complication that occurs in diabetes patients. In this study, we investigated the effect of cyclophosphamide (CTX) on expression of matrix metalloproteinases (MMP-9) and transforming growth factor-β1 (TGF-β1) in renal tissue of rats with DN. We found CTX significantly reduces KI and blood glucose levels, microalbuminuria, and blood urea nitrogen. It also decreases the expression of TGF-β1 and increases the expression of MMP-9. Our data suggest CTX may reduce the excretion of urine proteins, alleviate kidney hypertrophy, and reduce blood glucose level through regulation of TGF-β1 and MMP-9 gene expression.

Aims: We aimed to investigate cholecystokinin (CCK) release in pregnant women with and without hyperemesis gravidarum (HG)., Material and Methods: In this case-control study including 40 pregnant women with HG and 40 women with healthy uncomplicated pregnancies, serum CCK levels in addition to hematological, biochemical and hormonal parameters were investigated., Results: Serum CCK values were found to be significantly lower in pregnant women with HG (P < 0.001). Additionally, while serum blood urea nitrogen and free thyroxine levels were significantly higher, sodium, potassium, and thyroid stimulating hormone levels were significantly lower in women with HG than in control women. No correlation was detected between CCK and other parameters like ketonuria and thyroid function tests., Conclusions: CCK release has been found to be halved in pregnant women with HG, which supports the hypothesis that gastrointestinal motility is increased in pregnant women with HG. A causal effect remains to be confirmed., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

Currently, the mechanism(s) responsible for the regulation of urea transporter B (UT-B) expression levels in the epithelium of the rumen remain unclear. We hypothesized that rumen fermentation products affect ruminal UT-B expression. Therefore, the effects of short-chain fatty acids (SCFA), pH, ammonia, and urea on mRNA and protein levels of UT-B were assayed in primary rumen epithelial cell cultures and in rumen epithelium obtained from intact goats. In vitro, SCFA and acidic pH were found to synergetically stimulate both mRNA and protein expression of UT-B, whereas NH4Cl decreased mRNA and protein levels of UT-B at pH 6.8. Treatment with urea increased both levels at pH 7.4. When goats received a diet rich in nitrogen (N) and nonfiber carbohydrates (NFC), their rumen epithelium had higher levels of UT-B, and the rumen contained higher concentrations of SCFA and NH3-N with a lower pH. An increase in plasma urea-N concentration was also observed compared with the plasma of the goats that received a diet low in N and NFC. In a second feeding trial, goats that received a NFC-rich, but isonitrogenous, diet had higher mRNA and protein levels of UT-B, and higher levels of G protein-coupled receptor (GPR) 41 and GPR4, in their rumen epithelium. The ruminal concentrations of SCFA and NH3-N also increased, while a lower pH was detected. In contrast, the serum urea-N concentrations remained unchanged. These data indicate that ruminal SCFA and pH are key factors, via GPR4 and GPR41, in the dietary regulation of UT-B expression, and they have priority over changes in plasma urea., (Copyright © 2015 the American Physiological Society.)

Background: Risk stratification of acute kidney injury (AKI) is important for acute decompensated heart failure (ADHF). The aim of this study was to determine whether clinical markers, such as the blood urea nitrogen/creatinine ratio (BUN/Cr) or BUN or creatinine values alone, stratify the risk of AKI for mortality., Methods and Results: In all, 371 consecutive ADHF patients were enrolled in the study. AKI was defined as serum creatinine ≥0.3 mg/dl or a 1.5-fold increase in serum creatinine levels within 48 h. During ADHF therapy, AKI occurred in 99 patients; 55 patients died during the 12-month follow-up period. Grouping patients according to AKI and a median BUN/Cr at admission of 22.1 (non-AKI+low BUN/Cr, non-AKI+high BUN/Cr, AKI+low BUN/Cr, and AKI+high BUN/Cr groups) revealed higher mortality in the AKI+high BUN/Cr group (log-rank test, P<0.001). Cox's proportional hazard analysis revealed an association between AKI+high BUN/Cr and mortality, whereas the association with AKI+low BUN/Cr did not reach statistical significance. When patients were grouped according to AKI and median BUN or creatinine values at admission, AKI was associated with mortality, regardless of BUN or creatinine., Conclusions: The combination of AKI and elevated BUN/Cr, but not BUN or creatinine individually, is linked with an increased risk of mortality in ADHF patients, suggesting that the BUN/Cr is useful for risk stratification of AKI.

Three resistant starches (RSs), namely fibre of potatoes (FP), wrinkle pea starch (WPS), and high amylose maize starch (HAMS) with different dietary fibre contents, were supplemented in adults to evaluate their effects on urinary nitrogen and ammonia excretion as well as on faecal nitrogen excretion by means of lactose-[(15)N2]ureide ((15)N-LU) degradation. Twenty subjects received a regular diet either without or with the supplementation of FP, WPS, and HAMS in a randomized order. After administration of (15)N-LU, urine and faeces were collected over 48 and 72 h, respectively, whereas blood was collected after 6 h. The (15)N-abundances were measured by isotope ratio mass spectrometry. In comparison to the dry run, supplementation with RS significantly lowered renal (15)N-excretion (dry run: 43.2%, FP: 34.6%, WPS: 37.9%, HAMS: 36.4%) as well as the corresponding (15)NH3-excretion (dry run: 0.08%, FP: 0.06%, HAMS: 0.05%), clearly indicating a reduced colonic nitrogen generation at high dietary fibre intake.

Objective: Perioperative nutritional assessment is critically important to reflect nutritional management because liver transplantation (LTx) often is undertaken in patients with poor nutritional status. The aim of this study was to evaluate nutritional status, including the non-protein respiratory quotient (npRQ), resting energy expenditure (REE), nitrogen balance, and blood biochemical parameters in patients before and after LTx., Methods: Fourteen patients undergoing LTx and 10 healthy controls were enrolled in this study. The npRQ and REE were measured using indirect calorimetry before LTx and at 2, 3, and 4 wk after the procedure. Blood biochemistry and nitrogen balance calculated by 24-h urine collection were performed concurrently with indirect calorimetric measurement; the results were compared between the two groups., Results: Before LTx, npRQ was significantly lower and serum non-esterified fatty acid levels were significantly higher in the patients than in the controls. Furthermore, a negative nitrogen balance was observed in the patients. These, however, improved significantly at 4 wk after LTx. REE did not significantly increase compared with the preoperative values in recipients. Blood biochemistry showed gradually increasing levels of serum cholinesterase and albumin. These failed to reach to normal levels by 4 wk post-transplant., Conclusions: The findings revealed that improvement of nutritional metabolism after LTx may require 4 wk. Additional nutritional strategies, therefore, may be needed to minimize catabolic state during the early post-transplant period. Adequate, individualized nutritional guidance before and after LTx should be performed in these patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Winter severity can influence large herbivore populations through a reduction in maternal proteins available for reproduction. Nitrogen (N) isotopes in blood fractions can be used to track the use of body proteins in northern and montane ungulates. We studied 113 adult female caribou for 13 years throughout a series of severe winters that reduced population size and offspring mass. After these severe winters, offspring mass increased but the size of the population remained low. We devised a conceptual model for routing of isotopic N in blood in the context of the severe environmental conditions experienced by this population. We measured δ15N in three blood fractions and predicted the relative mobilization of dietary and body proteins. The δ 15N of the body protein pool varied by 4‰ and 46% of the variance was associated with year. Annual variation in δ15N of body protein likely reflected the fall/early winter diet and winter locations, yet 15% of the isotopic variation in amino acid N was due to body proteins. Consistent isotopic differences among blood N pools indicated that animals tolerated fluxes in diet and body stores. Conservation of body protein in caribou is the result of active exchange among diet and body N pools. Adult females were robust to historically severe winter conditions and prioritized body condition and survival over early investment in offspring. For a vagile ungulate residing at low densities in a predator-rich environment, protein restrictions in winter may not be the primary limiting factor for reproduction.

The concentration distribution around a growing nitrogen gas bubble in the blood and other bio tissues of divers who ascend to surface too quickly is obtained by Mohammadein and Mohamed model (2010) for variant and constant ambient pressure through the decompression process. In this paper, the growing of gas bubbles and concentration distribution under the effect of suction process are studied as a modification of Mohammadein and Mohamed model (zero suction). The growth of gas bubble is affected by ascent rate, tissue diffusivity, initial concentration difference, surface tension and void fraction. Mohammadein and Mohamed model (2010) is obtained as a special case from the present model. Results showed that, the suction process activates the systemic blood circulation and delay the growth of gas bubbles in the bio tissues to avoid the incidence of decompression sickness (DCS)., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Fractionation of N isotopes occurs in many metabolic reactions which causes tissue proteins to become enriched in ¹⁵N while urea (urine) is depleted in ¹⁵N relative to the diet. We investigated ¹⁵N enrichment of whole plasma and its relationship with feed conversion efficiency (FCE) in growing beef heifers (n 84) offered 2 kg/d of concentrates with grass silage ad libitum. Heifers were on average 299 (SD 48·3) d old and weighed 311 (SD 48·8) kg. Plasma was obtained on day 79 (n 84) of the experiment and from a subset of animals (n 20) on four occasions between days 16 and 79. Silage DM intake (DMI) averaged 4·1 (SD 0·74) kg/d and concentrate DMI was 1·72 kg/d. Mean mid-test live weight was 333 (SD 47·6) kg, daily gain was 0·53 (SD 0·183) kg, FCE (g live-weight gain/g DMI) was 0·09 (SD 0·028) and residual feed intake (RFI) was 0 (SD 0·428). N isotopic fractionation (Δ¹⁵N; plasma δ¹⁵N - diet δ¹⁵N) averaged 3·58 ‰ on day 79 (n 84) and 3·90 ‰ for the subset of heifers. There was no relationship between Δ¹⁵N and RFI. Plasma δ¹⁵N and Δ¹⁵N were related to both FCE (negative) and animal weight (positive) for the whole population, and repeatable for the subset of animals over four time points. These relationships of Δ¹⁵N with FCE and animal weight are consistent with the anticipated negative relationship with N-use efficiency. There is potential to use Δ¹⁵N to provide rapid, low-cost estimates of FCE in cattle.

Ingested dietary nutrients and feed energy are partitioned among tissues to sustain body growth. Based on the respective costs of the various metabolic pathways allowing use and storage of feed energy into cells, it may be theorized that daily meal frequency could affect growth, body composition or feed efficiency. This study aimed to determine the effects of daily meal frequency on nutrient partitioning, tissue metabolism and composition, and performance. Young growing pigs (30 kg BW) were offered a same amount of feed either in 2 (M2, n = 15) or 12 (M12, n = 16) meals per day during a 3-wk interventional period. Animals fed twice a day had an accelerated weight gain (+6.4%, P < 0.05) and exhibited a greater G:F (+4%, P = 0.03) than animals fed 12 meals per day during this period. Basal plasma concentrations of glucose, lactate, triglyceride, urea, and leptin were lower (P < 0.001) in M2 pigs than in M12 pigs. Meal frequency also changed (P < 0.001) the time-course profiles of plasma concentrations of glucose, insulin, and lactate in response to meal ingestion. A greater rise and a sharper fall in plasma glucose and insulin levels were observed in M2 pigs compared with M12 pigs. In both groups, similarities were observed in the postprandial time courses of plasma concentrations of insulin and of α-amino nitrogen (used as a measure of total AA). Despite these metabolic responses, tissue lipids, glycogen content, and enzyme activities participating in energy metabolism in muscle and liver were similar (P > 0.10) in both groups at the end of the trial. Percentage of perirenal fat in the body and depth of dorsal subcutaneous fat tissue were not affected by meal frequency, but kidney weight was lower (-18%, P < 0.001) in M2 pigs than in M12 pigs. Altogether, the less frequent daily meal intake improves the conversion of feed into weight gain, without marked modifications of tissue composition in young pigs.

Introduction: Perfluorocarbon emulsions (PFC) and nitric oxide (NO) releasing agents have on experimental basis demonstrated therapeutic properties in treating and preventing the formation of venous gas embolism as well as increased survival rate during decompression sickness from diving. The effect is ascribed to an increased solubility and transport capacity of respiratory gases in the PFC emulsion and possibly enhanced nitrogen washout through NO-increased blood flow rate and/or the removal of endothelial micro bubble nuclei precursors. Previous reports have shown that metabolic gases (i.e., oxygen in particular) and water vapor contribute to bubble growth and stabilization during altitude exposures. Accordingly, we hypothesize that the administration of PFC and NO donors upon hypobaric pressure exposures either (1) enhance the bubble disappearance rate through faster desaturation of nitrogen, or in contrast (2) promote bubble growth and stabilization through an increased oxygen supply., Methods: In anesthetized rats, micro air bubbles (containing 79% nitrogen) of 4-500 nl were injected into exposed abdominal adipose tissue. Rats were decompressed in 36 min to 25 kPa (~10,376 m above sea level) and bubbles studied for 210 min during continued oxygen breathing (FIO2 = 1). Rats were administered PFC, NO, or combined PFC and NO., Results: In all groups, most bubbles grew transiently, followed by a stabilization phase. There were no differences in the overall bubble growth or decay between groups or when compared with previous data during oxygen breathing alone at 25 kPa., Conclusion: During extreme altitude exposures, the contribution of metabolic gases to bubble growth compromises the therapeutic effects of PFC and NO, but PFC and NO do not induce additional bubble growth.

This study was aimed to evaluate the effect of alcoholic orange peel extract (OPE) on streptozotocin-induced diabetic nephropathy. Four weeks after the induction of diabetes, treatment with OPE (100 and 200 mg/kg) was further given for 4 weeks. Treatment with OPE 200 improved renal functions and significantly prevented the increase in creatinine, urea and blood urea nitrogen levels. Histological analysis of the kidneys revealed that tubulointerstitial fibrosis index was significantly decreased in OPE 200-treated group. The results indicated the prevention of diabetic nephropathy in rats by OPE treatment and suggest OPE as a potential treatment option.

Death is likely to result in very extensive biochemical changes in all body tissues due to lack of circulating oxygen, altered enzymatic reactions, cellular degradation, and cessation of anabolic production of metabolites. These biochemical changes may provide chemical markers for helping to more accurately determine the time since death (post-mortem interval), which is challenging to establish with current observation-based methodologies. In this study blood pH and changes in concentration of six metabolites (lactic acid, hypoxanthine, uric acid, ammonia, NADH and formic acid) were examined post-mortem over a 96 hour period in blood taken from animal corpses (rat and pig) and blood from rats and humans stored in vitro. The pH and the concentration of all six metabolites changed post-mortem but the extent and rate of change varied. Blood pH in corpses fell from 7.4 to 5.1. Concentrations of hypoxanthine, ammonia, NADH and formic acid all increased with time and these metabolites may be potential markers for post-mortem interval. The concentration of lactate increased and then remained at an elevated level and changes in the concentration were different in the rat compared to the human and pig. This is the first systematic study of multiple metabolic changes post-mortem and demonstrates the nature and extent of the changes that occur, in addition to identifying potential markers for estimating post-mortem interval.

Two studies were conducted to assess the effects of dietary protein and Lys reduction on growth performance, carcass quality, N excretion, and plasma N profile in growing-finishing pigs from 35 to 180 kg. The growing trial was conducted with 72 gilts and 72 barrows with 6 pens per treatment and 6 gilts or 6 barrows per pen. Four diets with the same DE and NE were compared: 1) control diet, 2) diet with protein content reduced by 3% units compared with the control diet and supplemented with Lys HCl to match the requirements according to the 2012 NRC (FLys), 3) diet similar to FLys for protein level but supplemented with only 50% of the Lys HCl provided with FLys (-50% FLys), and 4) diet similar to FLys and -50% Flys for protein level with microencapsulated Lys added to supply 20% of the Lys provided by FLys (-80% MLys). Pigs fed the FLys diet performed in a similar manner and showed similar carcass characteristics to the control pigs. Pigs fed the -50% FLys diet had the lightest BW (P < 0.01) as well as the lightest carcass (P = 0.02) and trimmed thigh (P = 0.04) weights. Pigs fed the -80% MLys diet showed growth performance and carcass characteristics similar to the control pigs. The N balance study was conducted with 8 barrows arranged in a double replicated 4 × 4 Latin square design. The control pigs had greater (P < 0.01) N intake and urinary and total N excretion compared with pigs fed the low-protein diets. The reduction of the dietary protein concentration by 3% units decreased total N excretion by an average of 24.5% and the greatest reduction of total N excretion was obtained by the -80% MLys diet (26.12%) compared with the control diet throughout the trial. No effect of dietary treatment was observed on the plasma concentrations of ammonia, urea, and total AA in the 80-kg pigs. Decreased plasma ammonia (P < 0.01) and urea (P = 0.03) concentrations were detected in the 120-kg pigs fed the low-protein diets. The 160-kg pigs fed the -80% MLys pigs had less total AA, indispensable AA in particular (P < 0.01), than pigs fed the other diets and decreased ammonia (P < 0.01) and urea (P = 0.05) concentrations than the control pigs. The results showed that the use of microencapsulated Lys, compared with both Lys HCl and dietary protein-bound Lys, can save CP and synthetic AA in diet formulation and can reduce N excretion in manure without adversely affecting the growth performance and carcass quality of heavy growing-finishing pigs.

Eimeria coecicola causes intestinal coccidiosis in rabbits and, thereby, enormous economic losses in rabbit farms. This study aimed to investigate the effect of intestinal coccidial infection, E. coecicola on metabolic status and growth of rabbits. Animals were allocated into two groups with eight rabbits each; one group was orally inoculated with saline and served as control while the other group was orally inoculated with 5 × 10(4) sporulated oocysts. On day 7 postinfection, fecal expulsion of E. coecicola oocysts is maximal (1.2 × 10(6) oocyst/g feces) and rabbits have lost approximately 23% of their weight. Infection induced a severe depletion in plasma growth hormone level. In addition, the energy metabolic status was significantly (P ≤ 0.05) altered by the infection as, both blood glucose and total lipid levels were significantly elevated with mutual depletion in carbohydrate stores in liver sections. Also, the thyroid-stimulating hormone and cortisol concentrations were raised as a consequence of the infection. Moreover, protein status was affected by the infection as both liver and plasma total proteins were significantly decreased with concurrent disturbance in the blood protein electrophoretic pattern and duplication of blood urea nitrogen concentration. Finally, the infection induced plasma electrolyte imbalance as indicated by a significant decrease in sodium, potassium, calcium, phosphorus, ferrous, and selenium ions. Our data suggested that the intestinal coccidial infection of rabbits with E. coecicola has serious effects on rabbit growth and metabolism and could disrupt endocrine and electrolyte homeostasis.