The estimation of protein equivalents of total nitrogen in Chinese CAPD patients: an explanatory study.

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.

Analysis of Serum Metabolomics in Rats with Osteoarthritis by Mass Spectrometry.

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.

Reduced uremic metabolites are prominent feature of sarcopenia, distinct from antioxidative markers for frailty.

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.

Nitrogen Balance after the Administration of a Prolonged-Release Protein Substitute for Phenylketonuria as a Single Dose in Healthy Volunteers.

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.

Feasibility of achieving different protein targets using a hypocaloric high-protein enteral formula in critically ill patients.

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.

Deaths related to nitrogen inhalation: Analytical challenges.

Dinitrogen (N2) has been increasingly connected to suicidal deaths. The analysis of N2 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 N2 intoxication described in forensic literature, we report the application of two approaches in order to quantify an excess of N2 in post-mortem whole blood collected from a case of suicide by nitrogen inhalation. N2 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 N2 was estimated by building a five-point N2 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 N2 in the sample vial. Percentage of N2 of the case was significantly higher than the post-mortem controls (p<0.05). The N2/O2 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 N2 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 N2 concentration in biological fluids. The presented methods can be rapidly and profitably applied with instrumentation normally available in forensic laboratories.

Biomarkers in critical care nutrition.

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.

Effect of Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), Capsules on Colistin-Induced Nephrotoxicity.

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.

An explicitly multi-component arterial gas embolus dissolves much more slowly than its one-component approximation.

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 (O2, N2, 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 N2-rich AGE must be done with care. While Helium is useful for preventing nitrogen narcosis which can arise in aggressive recompression therapy wherein the N2 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.

The role of oxidant stress and gender in the erythrocyte arginine metabolism and ammonia management in patients with type 2 diabetes.

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.

The Nitrogen Isotope Ratio Is a Biomarker of Yup'ik Traditional Food Intake and Reflects Dietary Seasonality in Segmental Hair Analyses.

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.

Effect of surgical or immune castration on postprandial nutrient profiles in male pigs.

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.

Postprandial insulin and nutrient concentrations in lipopolysaccharide-challenged growing pigs reared in thermoneutral and high ambient temperatures1.

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.

Nitrogen Washout and Venous Gas Emboli During Sustained vs. Discontinuous High-Altitude Exposures.

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.

Tear glucose, creatinine, and urea nitrogen concentrations in cats with normal or increased plasma concentrations.

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.

Pharmacokinetics of glycerol phenylbutyrate in pediatric patients 2 months to 2 years of age with urea cycle disorders.

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.

Exercise gas exchange in continuous-flow left ventricular assist device recipients.

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.

Effects of intraoperative nutrients administration on energy expenditure during general anesthesia.

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.

Saline is as effective as nitrogen scavengers for treatment of hyperammonemia.

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.