Absence of glutamine isotopic steady state: implications for the assessment of whole-body glutamine production rate

1998 ◽  
Vol 95 (3) ◽  
pp. 339 ◽  
Author(s):  
Bernadette A.C. VAN ACKER ◽  
Karel W.E. HULSEWÉ ◽  
Anton J.M. WAGENMAKERS ◽  
Nicolaas E.P. DEUTZ ◽  
Bernard K. VAN KREEL ◽  
...  
Keyword(s):  
Steady State ◽  
Production Rate ◽  
Whole Body ◽  
Glutamine Production

Absence of glutamine isotopic steady state: implications for the assessment of whole-body glutamine production rate

1998 ◽  
Vol 95 (3) ◽  
pp. 339-346 ◽  
Author(s):  
Bernadette A. C. VAN ACKER ◽  
Karel W. E. HULSEWÉ ◽  
Anton J. M. WAGENMAKERS ◽  
Nicolaas E. P. DEUTZ ◽  
Bernard K. VAN KREEL ◽  
...  
Keyword(s):  
Steady State ◽  
Abdominal Surgery ◽  
Whole Body ◽  
Infusion Time ◽  
Isotopic Enrichment ◽  
Gradual Reduction ◽  
Appearance Rate ◽  
Comparison Of The Results ◽  
Glutamine Production ◽  
Large Muscle

1.During infusion of [5-15N]glutamine in patients with gastrointestinal cancer we unexpectedly observed a gradual decrease in time of the appearance rate (Ra) of glutamine in plasma. Here we investigate whether the failure to achieve a plateau isotopic enrichment in plasma is, among other factors, due to incomplete equilibration of the glutamine tracer with the large intramuscular free glutamine pool. 2.Plasma and intramuscular glutamine enrichment were measured during 6–11 ;h infusions of L-[5-15N]glutamine and L-[1-13C]glutamine in post-absorptive patients admitted to hospital for elective abdominal surgery. L-[1-13C]Leucine and L-[ring-2H5]phenylalanine were infused to measure the proportion of glutamine appearing in plasma directly due to its release from protein. 3.The glutamine tracer entered muscle, but the rise in intramuscular glutamine enrichment was small, presumably as a result of the enormous size of the intramuscular glutamine pool and the limited speed of entry of glutamine into muscle. In each patient the intramuscular glutamine enrichment was lower than that in plasma (P < 0.001), and both increased with tracer infusion time (P < 0.001), indicating incomplete equilibration of the glutamine tracer. 4.A comparison of the results obtained by the two glutamine tracers indicated that recycling of the nitrogen label contributed to about 15% of the decrease in Ra. 5.There was a gradual reduction in the glutamine release from proteolysis, which contributed to 16–21% of the decline in Ra. 6.We conclude that slow equilibration of the glutamine tracer with the large muscle glutamine pool significantly contributes to the absence of isotopic steady state. Consequently, the appearance rate of glutamine in plasma measured during short tracer infusion periods (hours) considerably overestimates the whole-body glutamine flux.

Glutamine Production Rate and its Contribution to Urinary Ammonia in Normal Man

1982 ◽  
Vol 62 (3) ◽  
pp. 299-305 ◽  
Author(s):  
M. H. N. Golden ◽  
P. Jahoor ◽  
A. A. Jackson
Keyword(s):  
Production Rate ◽  
Ammonia Excretion ◽  
Whole Body ◽  
Acid Base ◽  
Male Adult ◽  
Body Protein ◽  
Acid Base Status ◽  
N Enrichment ◽  
Glutamine Production ◽  
Normal Acid

1. Glutamine [15N]amide was infused at a steady rate of 33.34 μmol/h into seven male adult volunteers who were in the fed state and normal acid-base status. 2. Plasma glutamine amide N enrichment and urinary ammonia N enrichment rose to a constant value within 3 h. 3. The glutamine production rate was 51.8 ± 7.9 mmol/h. 4. The total ammonia excretion rate was 0.87 mmol/h. Of this excreted ammonia 62.6 ± 9% was derived from the amide N atom of glutamine. 5. The excreted glutamine amide N (0.53 mmol/h) was only 1% of the glutamine production. If half the ammonia formed by the kidney is excreted in urine and half liberated into the renal vein in subjects with normal acid-base status [E. E. Owen & R. R. Robinson (1963) Journal of Clinical Investigation, 42, 263–276], then the kidney accounts for only 2% of glutamine disposal. 6. Whole body protein turnover, measured from the urinary [15N]ammonia enrichment, was 30.3 ± 7.7 g of N/day (2.8 g of protein day−1 kg−1).

Continuous Estimation of CO2 Production during Exercise

1997 ◽  
Vol 36 (04/05) ◽  
pp. 368-371
Author(s):  
R. Soma ◽  
Y. Yamamoto
Keyword(s):  
Fuzzy Logic ◽  
Steady State ◽  
Infusion Rate ◽  
Feedback System ◽  
Whole Body ◽  
Co2 Production ◽  
Cycle Exercise ◽  
Continuous Estimation ◽  
Breath Measurement ◽  
13Co2 Enrichment

Abstract.A new method was developed for continuous isotopic estimation of human whole body CO2 rate of appearance (Ra) during non-steady state exercise. The technique consisted of a breath-by-breath measurement of 13CO2 enrichment (E) and a real-time fuzzy logic feedback system which controlled NaH13CO3 infusion rate to achieve an isotopic steady state. Ra was estimated from the isotope infusion rate and body 13CO2 enrichment which was equal to E at the isotopic steady state. During a non-steady state incremental cycle exercise (5 w/min or 10 w/min), NaH13CO3 infusion rate was successfully increased by the action of feedback controller so as to keep E constant.

Cyclic Breathing Simulations in Large Scale Models of the Lung Airway From the Oronasal Opening to the Terminal Bronchioles

2012 ◽  
Author(s):  
D. Keith Walters ◽  
Greg W. Burgreen ◽  
Robert L. Hester ◽  
David S. Thompson ◽  
David M. Lavallee ◽  
...  
Keyword(s):  
Steady State ◽  
Boundary Conditions ◽  
Large Scale ◽  
Whole Body ◽  
Patient Specific ◽  
Cfd Simulations ◽  
Reduced Order ◽  
Scale Models ◽  
Steady State Simulation ◽  
Conducting Zone

Computational fluid dynamics (CFD) simulations were performed for unsteady periodic breathing conditions, using large-scale models of the human lung airway. The computational domain included fully coupled representations of the orotracheal region and large conducting zone up to generation four (G4) obtained from patient-specific CT data, and the small conducting zone (to G16) obtained from a stochastically generated airway tree with statistically realistic geometrical characteristics. A reduced-order geometry was used, in which several airway branches in each generation were truncated, and only select flow paths were retained to G16. The inlet and outlet flow boundaries corresponded to the oronasal opening (superior), the inlet/outlet planes in terminal bronchioles (distal), and the unresolved airway boundaries arising from the truncation procedure (intermediate). The cyclic flow was specified according to the predicted ventilation patterns for a healthy adult male at three different activity levels, supplied by the whole-body modeling software HumMod. The CFD simulations were performed using Ansys FLUENT. The mass flow distribution at the distal boundaries was prescribed using a previously documented methodology, in which the percentage of the total flow for each boundary was first determined from a steady-state simulation with an applied flow rate equal to the average during the inhalation phase of the breathing cycle. The distal pressure boundary conditions for the steady-state simulation were set using a stochastic coupling procedure to ensure physiologically realistic flow conditions. The results show that: 1) physiologically realistic flow is obtained in the model, in terms of cyclic mass conservation and approximately uniform pressure distribution in the distal airways; 2) the predicted alveolar pressure is in good agreement with previously documented values; and 3) the use of reduced-order geometry modeling allows accurate and efficient simulation of large-scale breathing lung flow, provided care is taken to use a physiologically realistic geometry and to properly address the unsteady boundary conditions.

Rock Stresses Induced by Flow of Fluids into Boreholes

1963 ◽  
Vol 3 (01) ◽  
pp. 85-94 ◽  
Author(s):  
P.R. Paslay ◽  
J.B. Cheatham
Keyword(s):  
Steady State ◽  
Pressure Gradient ◽  
Production Rate ◽  
Flow Rate ◽  
Rate Increase ◽  
Rock Material ◽  
Inside Surface ◽  
Axial Position ◽  
Air Drilling ◽  
Intermediate Surface

Abstract Rock stresses and steady-state flow rates induced by the pressure gradient associated with the flow of formation fluid into a borehole have been analytically determined for a permeable, elastic material saturated with an incompressible fluid. In this analysis, the material properties and loading are considered to he symmetric about the axis of the borehole and independent of axial position. For Case I the material is assumed to have uniform permeability in the radial direction, whereas for Case II the permeability is assumed to have been reduced in a localized region adjacent to the hole by either normal well completion and production operations or deliberate plugging during air drilling.Results of a numerical example indicate that, in the absence of plugging, the rock shear strength must be approximately two-thirds the formation fluid pressure in order to prevent rock failure. The required rock strength is high for small radial zones of plugging and decreases as the region of reduced permeability becomes larger; however, a depth of plugging can be reached beyond which there is no real gain in strength, although the flow rate can be further reduced. Introduction During normal production of oil from a well, it is often desirable to increase the production rate of the formation fluid by increasing the pressure gradient through the formation adjacent to the borehole. Depending upon the magnitude of this pressure gradient and strength of the rock material, this production-rate increase can cause sloughing of the hole wall. In many cases, the production-rate increase can result in excessive sand production, increased wear of production equipment, lost production time and expensive workover jobs.In addition, the phenomenon of increased rock bit penetration rate with the use of a gaseous instead of a liquid drilling fluid has been observed in oilfield drilling operations and experimentally demonstrated by various investigators for several years. The improvement obtained by employing this technique can be quite significant and offers a promising method for reducing drilling costs. However, air drilling is currently limited to geographical locations where high-capacity water-bearing formations are not encountered. This limitation has prevented widespread adoption of air-drilling techniques, because the water influx into the borehole interferes with efficient removal of the drilling cuttings and usually results in a condition such that the bit becomes "balled-up" or stuck in the hole.In an attempt to remove the water-intrusion limitation from air drilling, various chemical and mechanical water shut-off methods have been proposed. Goodwin and Teplitz suggested one such proposal whereby the permeability of the water - bearing rock structure was reduced in the vicinity of the borehole. Although the development of a shut-off method based upon this approach would certainly be welcomed by the oil industry, it is conceivable that, under certain conditions of the pressure gradient, strength of the rock material and depth of the modified permeability zone, a stress field can be created that will result in an unstable hole.As part of their study, an analytical solution is given for stresses in an idealized model of a hole and the surrounding rock material. The purpose of the present study is to extend the analysis of Goodwin and Teplitz to gain more insight into the details and consequences of excessive production rates and formation water shut-off. In particular, simplified models of these problems have been analytically examined, which makes possible the evaluation of the type of stress fields that can be anticipated as a result of these production and drilling practices.Both problems solved concern the determination of the steady-state volume flow rate of the formation fluid and the resulting steady-state stress and displacement distribution in a hollow, cylindrical configuration. The cylinder of Case I, corresponding to the production-rate problem, consists of a material with a constant permeability from the inside surface to the outside surface; the cylinder of Case II, corresponding to the water shut-off problem, consists of a material with a constant permeability from the inside surface to an intermediate concentric cylindrical surface and a second constant permeability from the intermediate surface to the outside surface. SPEJ P. 85^

scholarly journals Comparison of Infant Test-Weighing and Hourly Breast Expression in Measuring Maternal Milk Production (P11-041-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Dayna Roznowski ◽  
Erin Wagner ◽  
Sarah Riddle ◽  
Laurie Nommsen-Rivers
Keyword(s):  
Steady State ◽  
Production Rate ◽  
Milk Production ◽  
Production Capacity ◽  
Limits Of Agreement ◽  
Term Infants ◽  
Maternal Milk ◽  
Milk Output ◽  
Before And After ◽  
The Difference

Abstract Objectives Measuring maternal milk production is cumbersome. Our objectives were to: 1) confirm that milk production rate reaches steady state at hour 2 of hourly breast emptying; and 2) compare agreement in milk production when measured using the well-established test-weighing method versus the more efficient hourly breast emptying method (Lai, et al., Breastfeeding Medicine, 2010). Methods Eligible mothers were 4–10 weeks postpartum and exclusively breastfeeding their healthy, singleton, term infants. A subset of mothers test-weighed (TW) their infant (± 2 g) before and after breastfeeding for 48h. Within 1 week of TW, mothers had a morning visit at the research clinic for hourly breast expression measurements. Mothers emptied both breasts at baseline (h0), and 1, 2, and 3 hours after baseline (h1, h2, h3) using a hospital-grade pump. We recorded hourly milk output ± 1 g and adjusted production rate (g/h) to exact interval (minutes from end of previous to end of current expression). We used paired t-test to compare g/h at h3 versus h0, h1, and h2. We estimated mother's steady-state milk production rate (MPR, g/h) as mean (h2, h3). We used the Bland-Altman method for determining the 95% limits of agreement in measuring milk production (g/24h) using TW versus MPRx24. Results 23 mothers (65% primiparous) were 54 ± 14 days postpartum. Milk output was 185 ± 55 g at h0 and 60 ± 26, 47 ± 13, 44 ± 13 g/h at h1, h2, and h3, respectively. Mean paired difference (vs. h3) was significant at h0 and h1 (P < 0.05), but not at h2 (P > 0.05, h3 - h2 = 3 ± 10 g/h). In the subset with TW data (n = 16), mean TW milk output was 717 ± 119 g/24h, and mean MPRx24 was 1085 ± 300 g/24h. Mean difference, MPRx24 - TW [± 95% limits of agreement], was 368 [± 468] g/24h; and mean ratio, MPRx24/TW, was 1.5 [± 0.4]. Both difference and ratio significantly increased as MPR increased (P < 0.05). Conclusions Hourly milk production reaches steady state at h2; thus, mean (h2, h3) is a valid measure of current maternal milk production capacity. However, there was not homogeneous agreement between MPR and TW, and the 95% limits of agreement were very wide: -91 to 459 g/24h when expressed as the difference, and 0.9 to 1.9-fold as a ratio. Thus, MPR is feasible for researching variation in maternal milk production but not for researching variation in infant intake. Funding Sources None. Supporting Tables, Images and/or Graphs

scholarly journals Testing the Steady-State Fluctuation Relation in the Solar Photospheric Convection

Entropy ◽  
2020 ◽  
Vol 22 (7) ◽  
pp. 716
Author(s):  
Giorgio Viavattene ◽  
Giuseppe Consolini ◽  
Luca Giovannelli ◽  
Francesco Berrilli ◽  
Dario Del Moro ◽  
...  
Keyword(s):  
Steady State ◽  
Entropy Production ◽  
Production Rate ◽  
Local Level ◽  
Entropy Production Rate ◽  
Quasi Steady State ◽  
The Sun ◽  
Statistical Features ◽  
Local Entropy ◽  
Fluctuation Relation

The turbulent thermal convection on the Sun is an example of an irreversible non-equilibrium phenomenon in a quasi-steady state characterized by a continuous entropy production rate. Here, the statistical features of a proxy of the local entropy production rate, in solar quiet regions at different timescales, are investigated and compared with the symmetry conjecture of the steady-state fluctuation theorem by Gallavotti and Cohen. Our results show that solar turbulent convection satisfies the symmetries predicted by the fluctuation relation of the Gallavotti and Cohen theorem at a local level.

Tissue carbon dioxide stores: magnitude of acute change in the dog

1964 ◽  
Vol 206 (4) ◽  
pp. 887-890 ◽  
Author(s):  
S. F. Sullivan ◽  
R. W. Patterson ◽  
E. M. Papper
Keyword(s):  
Carbon Dioxide ◽  
Steady State ◽  
Dissociation Constant ◽  
Average Rate ◽  
Carbon Dioxide Tension ◽  
Whole Body ◽  
Limiting Factor ◽  
Acute Change ◽  
Washout Curves ◽  
Mixed Venous

Carbon dioxide washout curves were determined in hyperventilated dogs. Direct measurement of mixed venous carbon dioxide tension allowed calculation of changes in whole-body CO2 stores. The average whole-body CO2 dissociation constant in ten studies was 3.73 ml/kg mm. The limiting factor in reaching a new steady-state value was represented by a slow compartment in the washout curve. The average rate constant for this compartment was 0.062 min–1. The slowest compartment in this analysis has a 98% change in 1 hr, therefore the experimentally determined whole-body dissociation constant should closely approximate actual changes in tissue CO2 stores, excluding bone and fat.

scholarly journals 1396. Predictions of Isavuconazonium Sulfate Dosage in Patients Aged 6 Months: <18 Years by Physiologically Based Pharmacokinetic Modeling

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S429-S430 ◽  
Author(s):  
Amit Desai ◽  
Laura Kovanda ◽  
Christopher Lademacher ◽  
William Hope ◽  
Michael Neely ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Steady State ◽  
Allometric Scaling ◽  
Pbpk Model ◽  
Whole Body ◽  
Target Range ◽  
Independent Contractor ◽  
Physiologically Based Pharmacokinetic ◽  
Physiologically Based ◽  
Research Grant

Abstract Background Best practice to establish dosage regimens for “first-in-pediatric” clinical trials requires knowledge of efficacious and safe exposures in adults. Methods Pediatric equivalent doses were predicted for patients aged 6 months and &lt;18 years using physiologically based pharmacokinetic (PBPK) modeling, and compared with predictions by allometric scaling. All simulations were completed using PK-Sim®, which implements a whole-body PBPK model with 15 organs and appropriate maturation of anatomical and physiological parameters for children. The adult PBPK model was built using knowledge of drug physico-chemistry and clearance partitioning (CYP3A4, CYP3A5, glomerular filtration). PK data following IV (40, 80, 160 mg 60-minute infusion) and oral (100, 200, 400 mg capsule) doses in adults were used for initial model development. This model was validated by matching observed adult concentrations after multiple oral 200 mg doses. From this adult model, a virtual pediatric population (n = 4,600) from 6 months to &lt;18 years was created. Simulations with the pediatric model assessed optimal doses of isavuconazonium sulfate based on age and weight to achieve at least a median steady-state daily area under the curve (AUCss) of 100 mg hour/L, and the majority below 230 mg hour/L. These targets were derived from efficacy and safety data in clinical trials with adults. Results As shown in the figure, an isavuconazonium sulfate dose of 10 mg/kg is expected to result in AUCss within the target range for the majority of patients &gt;1 year old, in agreement with that predicted by allometry for patients aged 2–17 years. For patients aged 6 months to 1 year, a dose of 6 mg/kg predicts comparable exposures. Conclusion A proposed isavuconazonium sulfate dose of 10 mg/kg administered every 8 hours for the first 2 days and once daily thereafter is predicted to result in safe and efficacious steady state exposures in patients aged 1–17 years, similar to predictions from allometric scaling for patients aged 2–17 years. For subjects aged 6 months to 1 year, a dose of 6 mg/kg is predicted to achieve similar exposures. These doses should be tested in clinical trials to confirm. Disclosures A. Desai, Astellas Pharma, Inc.: Employee, Salary. L. Kovanda, Astellas Pharma, Inc.: Employee, Salary. C. Lademacher, Astellas Pharma, Inc.: Employee, Salary. W. Hope, F2G: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Astellas: Grant Investigator and Investigator, Grant recipient and Research grant. Pfizer: Grant Investigator, Research support. Gilead: Consultant and Scientific Advisor, Consulting fee. P. Bonate, Astellas Pharma, Inc.: Employee, Salary. A. Edginton, Astellas Pharma Global Development, Inc.: Independent Contractor, Consulting fee.

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