scholarly journals Control analysis applied to the whole body: control by body organs over plasma concentrations and organ fluxes of substances in the blood

1994 ◽  
Vol 297 (1) ◽  
pp. 115-122 ◽  
Author(s):  
G C Brown
Keyword(s):  
Steady State ◽  
Plasma Concentrations ◽  
Metabolic Control Analysis ◽  
The Body ◽  
Whole Body ◽  
Control Analysis ◽  
Physiological Control ◽  
Using Data ◽  
Control Coefficients

Metabolic control analysis is adapted as a method for describing and analysing the control by organs in the body over the fluxes and concentrations of substances carried in the blood. This physiological control analysis can most usefully be applied to substances with fluxes into and out of organs that are uniquely dependent only on their plasma concentrations. The organ flux of a substance is defined as the steady-state net flux of a substance into a particular organ. The organ flux control coefficients quantify the extent to which a particular organ controls the flux of a substance into the same or another particular organ. Organ concentration control coefficients quantify the extent to which an organ controls the steady-state concentration of a substance in the blood. The control coefficients are additive and obey summation, connectivity and branching theorems. Thus the control coefficients can be determined experimentally by measuring the sensitivities (elasticities) of organ fluxes to the plasma concentration of the substance. As an example of the application of these concepts, the control of ketone-body metabolism in vivo is analysed using data from the literature.

scholarly journals Integration of temporal analysis and control analysis of metabolic systems

1990 ◽  
Vol 269 (1) ◽  
pp. 255-259 ◽  
Author(s):  
J S Easterby
Keyword(s):  
Steady State ◽  
Transient Response ◽  
Temporal Analysis ◽  
Metabolic Control Analysis ◽  
Control Analysis ◽  
Control Coefficient ◽  
Temporal Control ◽  
Transient Time ◽  
Metabolic Systems ◽  
Control Coefficients

A theory is developed that integrates approaches to the analysis of pathway transient response and metabolic control analysis. A Temporal Control Coefficient is defined that is a measure of the system's transient response to modulation of enzyme activity or concentration. The approach allows for the analysis of the establishment of a steady state from rest, of the system's ‘agility’ of response to minor perturbations of a pre-existing steady state and of the macroscopic transition between steady states. In the last-mentioned case it is shown that, like the transient time itself, the control of transient response retains the property of independence from the mechanism of the transition. In consequence, the Temporal Control Coefficient can be defined in terms of the control properties of the initial and final states alone without reference to the mechanism of transition. A summation property is shown to apply to the Temporal Control Coefficients in each case. Connectivity relationships between elasticities and Temporal Control Coefficients are also established.

Regulation analysis of energy metabolism.

1997 ◽  
Vol 200 (2) ◽  
pp. 193-202 ◽  
Author(s):  
M D Brand
Keyword(s):  
Steady State ◽  
Energy Metabolism ◽  
Metabolic Control Analysis ◽  
Steady States ◽  
Control Analysis ◽  
Top Down ◽  
Down Regulation ◽  
Metabolic Systems ◽  
And Control ◽  
Control Coefficients

This paper reviews top-down regulation analysis, a part of metabolic control analysis, and shows how it can be used to analyse steady states, regulation and homeostasis in complex systems such as energy metabolism in mitochondria, cells and tissues. A steady state is maintained by the variables in a system; regulation is the way the steady state is changed by external effectors. We can exploit the properties of the steady state to measure the kinetic responses (elasticities) of reactions to the concentrations of intermediates and effectors. We can reduce the complexity of the system under investigation by grouping reactions into large blocks connected by a small number of explicit intermediates-this is the top-down approach to control analysis. Simple titrations then yield all the values of elasticities and control coefficients within the system. We can use these values to quantify the relative strengths of different internal pathways that act to keep an intermediate or a rate constant in the steady state. We can also use them to quantify the relative strengths of different primary actions of an external effector and the different internal pathways that transmit its effects through the system, to describe regulation and homeostasis. This top-down regulation analysis has been used to analyse steady states of energy metabolism in mitochondria, cells and tissues, and to analyse regulation of energy metabolism by cadmium, an external effector, in mitochondria. The combination of relatively simple experiments and new theoretical structures for presenting and interpreting the results means that top-down regulation analysis provides a novel and effective way to analyse steady states, regulation and homeostasis in intricate metabolic systems.

Computerized Tomography: A Perspective in the Pediatric Patient

PEDIATRICS ◽  
1977 ◽  
Vol 59 (2) ◽  
pp. 305-308
Author(s):  
Derek Harwood-Nash ◽  
Herman Grossman ◽  
Alvin Felman ◽  
John Kirkpatrick ◽  
Leonard Swischuk
Keyword(s):  
Computerized Tomography ◽  
Soft Tissues ◽  
Conventional Radiography ◽  
The United States ◽  
The Body ◽  
Whole Body ◽  
Central Research ◽  
X Ray ◽  
Whole Body Ct

Computerized tomography (CT), a technique conceptualized by Oldendorf in 19611 and developed by Hounsfield2 of EMI-Tronics Inc. (EMI) Central Research Laboratories, has proven to be a successful innovation in neuroradiology. Reviews by Ambrose3 in England and by Baker et al.4 and by New et al.5 in the United States have clearly demonstrated the value of this new modality in neuroradiological diagnosis. In 1975 Houser et al.6 and Harwood-Nash et al.7 provided the initial clinical and radiological data about CT in infants and children. More recently this technique has been extended to the study of tissues and organs in the body other than those in the head. This has been accomplished by modification of the original machine into a whole-body CT system. Early reviews by Ledley et al.8 and by Alfidi et al.9 suggest a significant potential for diagnosis of lesions in the abdomen, pelvis, and thorax. The advantages of CT are that it is less invasive than standard special diagnostic radiological procedures and that for the first time it provides in vivo information regarding the content and the characteristics of tissue composing organs and masses. DESCRIPTION OF EQUIPMENT In conventional radiography an image is made on radiographic film by an attenuated X-ray beam. In passing through a core of tissue, each ray of the beam is attenuated as it is absorbed and scattered by the tissue in its path. The intensity of the transmitted ray depends on the sum total of X-ray attenuation by all the different soft tissues in its path.

scholarly journals Buprenorphine Metabolites, Buprenorphine-3-glucuronide and Norbuprenorphine-3-glucuronide, Are Biologically Active

2011 ◽  
Vol 115 (6) ◽  
pp. 1251-1260 ◽  
Author(s):  
Sarah M. Brown ◽  
Michael Holtzman ◽  
Thomas Kim ◽  
Evan D. Kharasch
Keyword(s):  
Radioligand Binding ◽  
Competitive Inhibition ◽  
Antinociceptive Effect ◽  
Plasma Concentrations ◽  
Parent Drug ◽  
Biologically Active ◽  
Whole Body ◽  
Tail Flick ◽  
High Affinity

Background The long-lasting high-affinity opioid buprenorphine has complex pharmacology, including ceiling effects with respect to analgesia and respiratory depression. Plasma concentrations of the major buprenorphine metabolites norbuprenorphine, buprenorphine-3-glucuronide, and norbuprenorphine-3-glucuronide approximate or exceed those of the parent drug. Buprenorphine glucuronide metabolites pharmacology is undefined. This investigation determined binding and pharmacologic activity of the two glucuronide metabolites, and in comparison with buprenorphine and norbuprenorphine. Methods Competitive inhibition of radioligand binding to human μ, κ, and δ opioid and nociceptin receptors was used to determine glucuronide binding affinities for these receptors. Common opiate effects were assessed in vivo in SwissWebster mice. Antinociception was assessed using a tail-flick assay, respiratory effects were measured using unrestrained whole-body plethysmography, and sedation was assessed by inhibition of locomotion measured by open-field testing. Results Buprenorphine-3-glucuronide had high affinity for human μ (Ki [inhibition constant] = 4.9 ± 2.7 pM), δ (Ki = 270 ± 0.4 nM), and nociceptin (Ki = 36 ± 0.3 μM) but not κ receptors. Norbuprenorphine-3-glucuronide had affinity for human κ (Ki = 300 ± 0.5 nM) and nociceptin (Ki = 18 ± 0.2 μM) but not μ or δ receptors. At the dose tested, buprenorphine-3-glucuronide had a small antinociceptive effect. Neither glucuronide had significant effects on respiratory rate, but norbuprenorphine-3-glucuronide decreased tidal volume. Norbuprenorphine-3-glucuronide also caused sedation. Conclusions Both glucuronide metabolites of buprenorphine are biologically active at doses relevant to metabolite exposures, which occur after buprenorphine. Activity of the glucuronides may contribute to the overall pharmacology of buprenorphine.

Control analysis of photosynthetic sucrose synthesis: assignment of elasticity coefficients and flux-control coefficients to the cytosolic fructose 1,6-bisphosphatase and sucrose phosphate synthase

1989 ◽  
Vol 323 (1216) ◽  
pp. 327-338 ◽  
Keyword(s):  
Sucrose Phosphate Synthase ◽  
Control Analysis ◽  
Sucrose Synthesis ◽  
Flux Control ◽  
Fructose 1,6 Bisphosphatase ◽  
Flux Control Coefficients ◽  
Sucrose Phosphate ◽  
Control Coefficients ◽  
Phosphate Synthase

The use of elasticity coefficients and flux-control coefficients in a quantitative treatment of control is discussed, with photosynthetic sucrose synthesis as an example. Experimental values for elasticities for the cytosolic fructose 1,6-bisphosphatase and sucrose phosphate synthase are derived from their in vitro properties, and from an analysis of the in vivo relation between fluxes and metabolite levels. An empirical factor α , describing the response of the fructose 2,6-bisphosphate regulator cycle to fructose 6-phosphate is described, and an expression is derived relating α to the elasticities of the enzymes involved in this regulator cycle. The in vivo values for elasticities and α are then used in a modified form of the connectivity theorem to estimate the flux control coefficients of the cytosolic fructose 1,6-bisphosphatase and sucrose phosphate synthase during rapid photosynthetic sucrose synthesis.

scholarly journals Follow-up of GK rats during prediabetes highlights increased insulin action and fat deposition despite low insulin secretion

2008 ◽  
Vol 294 (1) ◽  
pp. E168-E175 ◽  
Author(s):  
Jamileh Movassat ◽  
Danièle Bailbé ◽  
Cécile Lubrano-Berthelier ◽  
Françoise Picarel-Blanchot ◽  
Eric Bertin ◽  
...  
Keyword(s):  
Body Composition ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Cell Mass ◽  
The Body ◽  
Whole Body ◽  
Β Cell ◽  
Gk Rats

The adult Goto-Kakizaki (GK) rat is characterized by impaired glucose-induced insulin secretion in vivo and in vitro, decreased β-cell mass, decreased insulin sensitivity in the liver, and moderate insulin resistance in muscles and adipose tissue. GK rats do not exhibit basal hyperglycemia during the first 3 wk after birth and therefore could be considered prediabetic during this period. Our aim was to identify the initial pathophysiological changes occurring during the prediabetes period in this model of type 2 diabetes (T2DM). To address this, we investigated β-cell function, insulin sensitivity, and body composition in normoglycemic prediabetic GK rats. Our results revealed that the in vivo secretory response of GK β-cells to glucose is markedly reduced and the whole body insulin sensitivity is increased in the prediabetic GK rats in vivo. Moreover, the body composition of suckling GK rats is altered compared with age-matched Wistar rats, with an increase of the number of adipocytes before weaning despite a decreased body weight and lean mass in the GK rats. None of these changes appeared to be due to the postnatal nutritional environment of GK pups as demonstrated by cross-fostering GK pups with nondiabetic Wistar dams. In conclusion, in the GK model of T2DM, β-cell dysfunction associated with increased insulin sensitivity and the alteration of body composition are proximal events that might contribute to the establishment of overt diabetes in adult GK rats.

scholarly journals Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations1: computer simulation and Metabolic Control Analysis

1999 ◽  
Vol 342 (3) ◽  
pp. 597-604 ◽  
Author(s):  
Peter J. MULQUINEY ◽  
Philip W. KUCHEL
Keyword(s):  
Computer Simulation ◽  
Metabolic Control ◽  
Energy Demand ◽  
Feedback Inhibition ◽  
Oxygen Affinity ◽  
Metabolic Control Analysis ◽  
Product Inhibition ◽  
Control Analysis ◽  
And Control

This is the third of three papers [see also Mulquiney, Bubb and Kuchel (1999) Biochem. J. 342, 565-578; Mulquiney and Kuchel (1999) Biochem. J. 342, 579-594] for which the general goal was to explain the regulation and control of 2,3-bisphosphoglycerate (2,3-BPG) metabolism in human erythrocytes. 2,3-BPG is a major modulator of haemoglobin oxygen affinity and hence is vital in blood oxygen transport. A detailed mathematical model of erythrocyte metabolism was presented in the first two papers. The model was refined through an iterative loop of experiment and simulation and it was used to predict outcomes that are consistent with the metabolic behaviour of the erythrocyte under a wide variety of experimental and physiological conditions. For the present paper, the model was examined using computer simulation and Metabolic Control Analysis. The analysis yielded several new insights into the regulation and control of 2,3-BPG metabolism. Specifically it was found that: (1) the feedback inhibition of hexokinase and phosphofructokinase by 2,3-BPG are equally as important as the product inhibition of 2,3-BPG synthase in controlling the normal in vivo steady-state concentration of 2,3-BPG; (2) H+ and oxygen are effective regulators of 2,3-BPG concentration and that increases in 2,3-BPG concentrations are achieved with only small changes in glycolytic rate; (3) these two effectors exert most of their influence through hexokinase and phosphofructokinase; (4) flux through the 2,3-BPG shunt changes in absolute terms in response to different energy demands placed on the cell. This response of the 2,3-BPG shunt contributes an [ATP]-stabilizing effect. A ‘cost’ of this is that 2,3-BPG concentrations are very sensitive to the energy demand of the cell and; (5) the flux through the 2,3-BPG shunt does not change in response to different non-glycolytic demands for NADH.

Direct Determination of the Body Content of Radionuclides: Abstract

2003 ◽  
Vol 3 (1) ◽  
pp. 9-9
Author(s):  
R. Griffith ◽  
H. Bergmann ◽  
F. A. Fry ◽  
D. Hickman ◽  
J.-L. Genicot ◽  
...  
Keyword(s):  
Direct Measurement ◽  
Direct Determination ◽  
The Body ◽  
Whole Body ◽  
Control Measurement ◽  
In Vivo Measurement ◽  
Calibration Methods ◽  
Partial Body ◽  
And Control

Previous ICRU reports have dealt with the formulation and properties of tissue substitutes and phantoms that are used to calibrate in vivo measurement systems. This report provides guidance on the overall process of the direct measurement of radionuclides in the human body for radiation protection and medical applications. It addresses the detectors and electronics used for the measurement; methods of background reduction and control; measurement geometries for whole body, partial body or organ counting; physical and mathematical calibration methods; data analysis; and quality assurance. It is directed to readers who need practical advice on the establishment and operation of direct measurement facilities.

Sign in / Sign up

Export Citation Format

Share Document