Kinetic analysis of zinc metabolism and its regulation in normal humans

1986 ◽  
Vol 251 (2) ◽  
pp. R398-R408 ◽  
Author(s):  
M. E. Wastney ◽  
R. L. Aamodt ◽  
W. F. Rumble ◽  
R. I. Henkin
Keyword(s):  
Compartmental Model ◽  
Additional Data ◽  
Normal Subjects ◽  
The Body ◽  
Whole Body ◽  
Zinc Metabolism ◽  
Zinc Intake ◽  
Normal Humans ◽  
Taste And Smell ◽  
Oral Supplement

Zinc metabolism was studied in 32 normal volunteers after oral (n = 25) or intravenous (n = 7) administration of 65Zn. Data were collected from the blood, urine, feces, whole body, and over the liver and thigh regions for 9 mo while the subjects consumed their regular diets (containing 10 mg Zn ion/day) and for an additional 9 mo while the subjects received an exogenous oral supplement of 100 mg Zn ion/day. Data from each subject were fitted by a compartmental model for zinc metabolism that was developed previously for patients with taste and smell dysfunction. These data from normal subjects were used to determine the absorption, distribution, and excretion of zinc and the mass of zinc in erythrocytes, liver, thigh, and whole body. By use of additional data obtained from the present study, the model was refined further such that a large compartment, which was previously determined to contain 90% of the body zinc, was subdivided into two compartments to represent zinc in muscle and bone. When oral zinc intake was increased 11-fold three new sites of regulation of zinc metabolism were identified in addition to the two sites previously defined in patients with taste and smell dysfunction (absorption of zinc from gut and excretion of zinc in urine). The three new sites are exchange of zinc with erythrocytes, release of zinc by muscle, and secretion of zinc into gut. Regulation at these five sites appears to maintain some tissue concentrations of zinc when dietary zinc increases.

Compartmental model of leucine kinetics in humans

1991 ◽  
Vol 261 (4) ◽  
pp. E539-E550 ◽  
Author(s):  
C. Cobelli ◽  
M. P. Saccomani ◽  
P. Tessari ◽  
G. Biolo ◽  
L. Luzi ◽  
...  
Keyword(s):  
Stable Isotope ◽  
Compartmental Model ◽  
Linear Time ◽  
A Priori ◽  
Normal Subjects ◽  
Whole Body ◽  
Constant Infusion ◽  
Individual Subject ◽  
Domain Of Validity

The complexity of amino acid and protein metabolism has limited the development of comprehensive, accurate whole body kinetic models. For leucine, simplified approaches are in use to measure in vivo leucine fluxes, but their domain of validity is uncertain. We propose here a comprehensive compartmental model of the kinetics of leucine and alpha-ketoisocaproate (KIC) in humans. Data from a multiple-tracer administration were generated with a two-stage (I and II) experiment. Six normal subjects were studied. In experiment I, labeled leucine and KIC were simultaneously injected into plasma. Four plasma leucine and KIC tracer concentration curves and label in the expired CO2 were measured. In experiment II, labeled bicarbonate was injected into plasma, and labeled CO2 in the expired air was measured. Radioactive (L-[1-14C]leucine, [4,5-3H]KIC, [14C]bicarbonate) and stable isotope (L-[1-13C]leucine, [5,5,5-2H3]KIC, [13C]bicarbonate) tracers were employed. The input format was a bolus (impulse) dose in the radioactive case and a constant infusion in the stable isotope case. A number of physiologically based, linear time-invariant compartmental models were proposed and tested against the data. The model finally chosen for leucine-KIC kinetics has 10 compartments: 4 for leucine, 3 for KIC, and 3 for bicarbonate. The model is a priori uniquely identifiable, and its parameters were estimated with precision from the five curves of experiment I. The separate assessment of bicarbonate kinetics (experiment II) was shown to be unnecessary. The model defines masses and fluxes of leucine in the organism, in particular its intracellular appearance from protein breakdown, its oxidation, and its incorporation into proteins. An important feature of the model is its ability to estimate leucine oxidation by resolving the bicarbonate model in each individual subject. Finally, the model allows the assessment of the domain of validity of the simpler commonly used models.

Perception of passive whole-body rotations in the absence of neck and body proprioception

1995 ◽  
Vol 74 (5) ◽  
pp. 2216-2219 ◽  
Author(s):  
J. Blouin ◽  
J. L. Vercher ◽  
G. M. Gauthier ◽  
J. Paillard ◽  
C. Bard ◽  
...  
Keyword(s):  
Normal Subjects ◽  
The Body ◽  
Whole Body ◽  
Neck Muscle ◽  
Body Rotation ◽  
Gaze Shift ◽  
The Third ◽  
Muscle Proprioception ◽  
Patient Reported ◽  
Accurate Perception

1. This study investigated whether accurate perception of body rotation after passive horizontal whole-body rotations in the dark requires the integration of both vestibular and neck-body proprioceptive signals. 2. In the first experiment, the gain of the vestibuloocular reflex (VOR) of normal subjects ("controls") and of a patient without proprioception of the neck and body muscles was assessed by the use of pulse and sinusoidal stimulation. In the second experiment, the subjects reported verbally the magnitude of the body rotations. Finally, in the third experiment, they shifted gaze to the position fixated before the rotation ("vestibular memory-contingent saccades" paradigm). 3. The VOR gain of the patient was similar to that of controls, although the body rotations of the patient were largely overestimated, regardless of whether the patient reported the perceived magnitude verbally or through a gaze shift toward the position gazed at before the rotation. 4. These results suggest that neck muscle proprioception contributes to the vestibular signal calibration at the perceptual level necessary for determining body orientation accurately after rotations in the dark.

Coordination of a step with a reach

2000 ◽  
Vol 10 (2) ◽  
pp. 59-73 ◽  
Author(s):  
Linda Daghestani ◽  
John H. Anderson ◽  
Martha Flanders
Keyword(s):  
Visual Cues ◽  
Body Movement ◽  
Reference Signal ◽  
Normal Subjects ◽  
The Body ◽  
Whole Body ◽  
Control Subjects ◽  
Hand Coordination ◽  
Spatial Positioning ◽  
Target Locations

Although natural reaching behavior can easily include forward body movement, most laboratory studies of reaching have constrained the body to be stationary. Recently, however, it has been shown that normal subjects exhibit a different pattern of errors when attempting to pinpoint remembered target locations, depending on whether or not the reach includes a step. In the study of Flanders et al. [1], these errors appeared to be due to the strategy of eye/head/hand coordination which normally comes into play when the body is moving toward the target. Since the spatial positioning of the head was found to partially explain the errors in hand placement, the present study examined the movements of patients with bilateral vestibular deficits in order to further analyze the whole-body coordination. Somewhat surprisingly, the patients exhibited the same pattern of head movement and the same errors in hand placement as did the control subjects. Nevertheless, the patients' movements clearly exhibited evidence for an abnormal decomposition of elbow extension and trunk rotation. Furthermore the patients' (spatial) hand paths were significantly more curved than those of control subjects and, only in the patients, paths to remembered targets were significantly more curved than paths to visible targets. Thus for movements to remembered targets, the patients tended to move the hand to the same incorrect spatial positions as control subjects but spatiotemporal aspects of the arm and body movement differed. The results are consistent with the idea that vestibular patients are overly dependent upon visual cues, and support the hypothesis that this stepping and reaching behavior is largely dependent upon a visual reference signal.

Increased leucine flux in short-term fasted human subjects: evidence for increased proteolysis

1984 ◽  
Vol 247 (3) ◽  
pp. E323-E327 ◽  
Author(s):  
E. Tsalikian ◽  
C. Howard ◽  
J. E. Gerich ◽  
M. W. Haymond
Keyword(s):  
Human Subjects ◽  
Normal Subjects ◽  
Whole Body ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Short Term ◽  
Body Protein ◽  
Apparent Decrease ◽  
Normal Humans ◽  
Plasma Leucine

Plasma leucine concentration increases with short-term fasting in normal humans. In previous studies using an 18-h constant infusion of [2H3]leucine, a 15% decrease in the rate of appearance (Ra) of leucine was observed between 15 and 30 h of fasting. However, incorporation of labeled leucine into and subsequent release from body protein could result in an apparent decrease in leucine Ra. The present studies were undertaken to determine the rate of leucine N and carbon flux in short-term fasted human subjects in using an experimental design that would minimize potential recycling of label. Six normal subjects were infused with [15N]- and [2H3]leucine for two 4-h periods (0600 to 1000 h and 2000 to 2400 h) during a 30-h fast. Between the 15th and 30th h of fasting, plasma leucine concentration (102 +/- 10 to 169 +/- 18 microM, P less than 0.01) and leucine C (1.46 +/- 0.05 to 1.64 +/- 0.10 mumol X kg-1 X min-1, P less than 0.05) and leucine N (1.93 +/- 0.14 to 2.49 +/- 0.26 mumol X kg-1 X min-1, P less than 0.05) flux increased, whereas the metabolic clearance rates of leucine C and N decreased (P less than 0.01 and less than 0.05, respectively). Therefore, when isotope recycling is minimized with short periods of isotope infusion, leucine flux increases between 15 and 30 h of fasting. Because the only source of leucine in the postabsorptive periods is body protein, we conclude that the rate of whole-body proteolysis is increased in short-term fasting in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Iron Metabolism after Renal Transplantation

1973 ◽  
Vol 44 (1) ◽  
pp. 27-32 ◽  
Author(s):  
K. Boddy ◽  
G. Will ◽  
D. H. Lawson ◽  
Priscilla C. King ◽  
A. L. Linton
Keyword(s):  
Renal Failure ◽  
Renal Transplantation ◽  
Chronic Renal Failure ◽  
Iron Metabolism ◽  
Oral Absorption ◽  
Normal Subjects ◽  
The Body ◽  
Whole Body ◽  
The Mean

1. The oral absorption and the rate of loss from the body of radioactive iron were measured by whole-body monitoring in patients with functioning renal homografts. The incorporation of radioactive iron into erythrocytes was also measured. 2. The results were compared with corresponding values in normal subjects and in non-dialysed and dialysed patients with chronic renal failure. 3. The mean oral absorption and incorporation into erythrocytes of radioactive iron was intermediate between that of normal subjects and of both non-dialysed and dialysed patients with chronic renal failure. 4. The mean rate of loss from the body was not significantly different from that in normal subjects and non-dialysed patients with chronic renal failure but it was significantly less than that in dialysed patients.

Origin and disposal of 1,5-anhydroglucitol, a major polyol in the human body

1992 ◽  
Vol 263 (2) ◽  
pp. E268-E273 ◽  
Author(s):  
T. Yamanouchi ◽  
Y. Tachibana ◽  
H. Akanuma ◽  
S. Minoda ◽  
T. Shinohara ◽  
...  
Keyword(s):  
Human Body ◽  
De Novo ◽  
Normal Subjects ◽  
The Body ◽  
Diabetic Patients ◽  
Food Ingestion ◽  
De Novo Synthesis ◽  
The Mean ◽  
Kinetics Of ◽  
Oral Supplement

The origin and disposal of 1,5-anhydro-D-glucitol (AG), one of the main polyols found in the human body, was studied in normal subjects and diabetic patients. AG was detected in various kinds of foods. The mean AG supplement through foods was estimated to be approximately 4.38 mg/day, which was compatible with that calculated in a food analysis (average 0.22 mg AG/100 kcal in Japanese foods) on eight healthy subjects. The mean AG excretion in urine was approximately 4.76 mg/day in these subjects. Excretion into stools was negligible. From observations on the patients without oral supplement of AG, 0.4 mg of daily de novo synthesis of AG was strongly suggested. It was also implied that urinary AG excretion occurred soon after food ingestion and that its amount was closely correlated with daily supplement through foods. Thus the fundamental kinetics of AG were recognized as follows: 1) AG in the body originates mainly from foods and is well absorbed in the intestine, 2) AG is little degraded and metabolized in the body, and 3) an equilibrium exists between oral supplement plus a small but steady amount of de novo synthesis and excretion in urine.

Iron Metabolism in Patients with Chronic Renal Failure

1970 ◽  
Vol 39 (1) ◽  
pp. 115-121 ◽  
Author(s):  
K. Boddy ◽  
D. H. Lawson ◽  
A. L. Linton ◽  
G. Will
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Iron Deficiency ◽  
Iron Metabolism ◽  
Normal Subjects ◽  
The Body ◽  
Whole Body ◽  
Red Cell ◽  
Monitoring Technique

1. Iron metabolism has been investigated in patients suffering from chronic renal failure, using a whole body monitoring technique. 2. Absorption of labelled inorganic iron was decreased. 3. Radio-iron was lost from the body at a rate comparable to that found in normal subjects. 4. The red cell incorporation of radioactive iron was diminished. 5. The results suggest that anaemia in these patients was due to decreased erythropoiesis and not due to iron deficiency despite the evidence of markedly abnormal iron handling presented.

Analysis of 47Ca Kinetics in Normal Subjects by Means of a Compartmental Model with a Non-Exchangeable Plasma Calcium Fraction

1979 ◽  
Vol 56 (6) ◽  
pp. 523-532 ◽  
Author(s):  
B. L. Wajchenberg ◽  
P. R. Leme ◽  
M. N. L. Ferreira ◽  
J. Modesto Filho ◽  
R. R. Pieroni ◽  
...  
Keyword(s):  
Compartmental Model ◽  
Kinetic Studies ◽  
Compartment Model ◽  
Normal Subjects ◽  
Plasma Calcium ◽  
Whole Body ◽  
Adult Males ◽  
Counting Data ◽  
Exchangeable Fraction ◽  
Plasma Compartment

1. 47Ca kinetic studies were performed in eight normal young adult males. Plasma, urinary and faecal stable and radioactive calcium and whole-body radioactivity were measured for up to 40 days after intravenous administration of the tracer. 2. The plasma radioactivity data could be fitted to the sum of four exponentials corresponding to a four-compartment model, but this model did not account for the consistently greater 47Ca specific radioactivities in plasma relative to those in urine at the same time in five of the subjects. 3. A non-exchangeable fraction of plasma calcium estimated as 5% of the mass in the plasma compartment was postulated to account for this finding. 4. An estimate of the insensible losses of calcium was obtained from the whole-body radioactivity counting data.

Kinetic analysis of zinc metabolism in humans after simultaneous administration of 65Zn and 70Zn

1991 ◽  
Vol 260 (1) ◽  
pp. R134-R141 ◽  
Author(s):  
M. E. Wastney ◽  
I. G. Gokmen ◽  
R. L. Aamodt ◽  
W. F. Rumble ◽  
G. E. Gordon ◽  
...  
Keyword(s):  
Blood Cells ◽  
Compartmental Model ◽  
Zinc Concentration ◽  
Whole Body ◽  
Zinc Metabolism ◽  
Zinc Absorption ◽  
Simultaneous Administration ◽  
Human Volunteers ◽  
Radioactive Zinc ◽  
Normal Human

Zinc kinetics were studied and compared after oral simultaneous administration of two tracers, radioactive (65Zn) and stable (70Zn) isotope, to four normal human volunteers. Both tracers and zinc concentration were measured in plasma, red blood cells (RBC), urine, and feces for up to 78 days. Radioactive zinc was also measured by external counting over whole body, liver, and thigh. Data from each individual were analyzed using a compartmental model for zinc metabolism. Values calculated for absorption, fractional zinc excretion in urine, exchange with RBC, and secretion into gut using 70Zn data did not differ from values calculated using 65Zn data. Results show that human zinc metabolism can be investigated using stable isotopes as tracers to determine parameters of whole body zinc metabolism, including zinc absorption, excretion, and secretion.

Sign in / Sign up

Export Citation Format

Share Document