A minimal model for human whole body cholesterol metabolism

1993 ◽  
Vol 265 (3) ◽  
pp. E513-E520
Author(s):  
R. E. Ostlund
Keyword(s):  
Minimal Model ◽  
Cholesterol Metabolism ◽  
Specific Activity ◽  
Clinical Investigation ◽  
Plasma Cholesterol ◽  
Fractional Excretion ◽  
Compartment Model ◽  
The Body ◽  
Whole Body ◽  
Mean Values

Important work by others has shown that human whole body cholesterol metabolism can be described by a three-compartment model computed from plasma cholesterol specific activity after an intravenous infusion of labeled cholesterol. However, some parameters of that model cannot be estimated precisely [coefficient of variation (CV) 15-19% after 40 wk of follow-up], making its use in routine clinical investigation difficult. On the other hand, a simpler two-compartment model can be calculated with excellent precision from only 10 wk of data (CV 2-8%), but its parameters are inaccurate (for example, the size of the central pool is overestimated by 20%, and the rate constant for fractional excretion of cholesterol from the body is underestimated by 15%). Thus both three-compartment and two-compartment models of cholesterol turnover have important limitations. An alternative is provided by a minimal model that takes advantage of the increased precision expected in the solution of models with fewer parameters. A three-compartment structure is used, but only four (rather than 6 or more) parameters are calculated: the mass of the rapidly mixing central cholesterol compartment, the fractional rate of cholesterol elimination from the body, and the average forward and reverse rate constants for cholesterol transfer between the rapid compartment and both slower compartments. Each of these parameters can be determined unambiguously (without the need to use a minimum or maximum estimate), accurately (mean values within 2% of theory), and with precision (CV 3-13%).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Biomechanical Aspects of the Foot Arch, Body Balance and Body Weight Composition of Boys Training Football

2021 ◽  
Vol 18 (9) ◽  
pp. 5017
Author(s):  
Joanna M. Bukowska ◽  
Małgorzata Jekiełek ◽  
Dariusz Kruczkowski ◽  
Tadeusz Ambroży ◽  
Jarosław Jaszczur-Nowicki
Keyword(s):  
Body Composition ◽  
Body Height ◽  
Study Groups ◽  
The Body ◽  
Whole Body ◽  
Training Methods ◽  
Training Experience ◽  
Mean Values ◽  
Significance Level ◽  
Body Balance

Background: The aim of the study is to assess the body balance and podological parameters and body composition of young footballers in the context of the control of football training. Methods: The study examined the distribution of the pressure of the part of the foot on the ground, the arch of the foot, and the analysis of the body composition of the boys. The pressure center for both feet and the whole body was also examined. The study involved 90 youth footballers from Olsztyn and Barczewo in three age groups: 8–10 years, 11–13 years old, and 14–16 years. The study used the Inbody 270 body composition analyzer and the EPSR1, a mat that measures the pressure distribution of the feet on the ground. Results: The results showed statistically significant differences in almost every case for each area of the foot between the groups of the examined boys. The most significant differences were observed for the metatarsal area and the left heel. In the case of stabilization of the whole body, statistically significant differences were noted between all study groups. In the case of the body composition parameters, in the examined boys, a coherent direction of changes was noticed for most of them. The relationships and correlations between the examined parameters were also investigated. The significance level in the study was set at p < 0.05. Conclusions: Under the training rigor, a statistically significant increase in stability was observed with age. The total length of the longitudinal arch of both feet of the examined boys showed a tendency to flatten in direct proportion to the age of the examined boys. Mean values of the body composition parameters reflect changes with the ontogenetic development, basic somatic parameters (body height and weight) and training experience, and thus with the intensity and volume of training. This indicates a correct training process that does not interfere with the proper development of the body in terms of tissue and biochemical composition.

Extracellular and intracellular carbon dioxide concentration as a function of temperature in the toad Bufo marinus.

1994 ◽  
Vol 195 (1) ◽  
pp. 345-360 ◽  
Author(s):  
J N Stinner ◽  
D L Newlon ◽  
N Heisler
Keyword(s):  
Body Temperature ◽  
Extracellular Fluid ◽  
Carbon Dioxide Concentration ◽  
The Body ◽  
Whole Body ◽  
Mean Values ◽  
Temperature Changes ◽  
Fluid Compartment ◽  
Average Change ◽  
Higher Temperature

Previous studies of reptiles and amphibians have shown that changing the body temperature consistently produces transient changes in the respiratory exchange ratio (RE) and, hence, changes in whole-body CO2 stores, and that the extracellular fluid compartment contributes to the temperature-related changes in CO2 stores. The purpose of this study was to determine whether the intracellular fluid compartment contributes to the changes in CO2 stores in undisturbed resting cane toads. Increasing body temperature from 10 to 30 degrees C temporarily elevated RE, and returning body temperature to 10 degrees C temporarily lowered RE. The estimated average change in whole-body CO2 stores associated with the transient changes in RE was 1.0 +/- 0.8 mmol kg-1 (+/- S.D., N = 6). Plasma [CO2] and, thus, extracellular fluid [CO2], were unaffected by the temperature change. Plasma calcium levels were also unaffected, so that bone CO2 stores did not contribute to changes in whole-body CO2 stores. Intracellular [CO2] was determined for the lung, oesophagus, stomach, small intestine, liver, ventricle, red blood cells, skin and 14 skeletal muscles. [CO2] was significantly lower (P &lt; 0.05) at higher temperature in 10 of these, and seven others, although not statistically significant (P &gt; 0.05), had mean values at least 0.5 mmol kg-1 lower at the higher temperature. The average change in intracellular [CO2] for all tissues examined was -0.165 mmol kg-1 degrees C-1. We conclude that, in cane toads, the temperature-related transients in RE result from intracellular CO2 adjustments, that different tissues have unique intracellular CO2/temperature relationships, and that a combination of respiratory and ion-exchange mechanisms is used to adjust pH as temperature changes.

scholarly journals Compromised Intestinal Lipid Absorption in Mice with a Liver-Specific Deficiency of Liver Receptor Homolog 1

2007 ◽  
Vol 27 (23) ◽  
pp. 8330-8339 ◽  
Author(s):  
Chikage Mataki ◽  
Benjamin C. Magnier ◽  
Sander M. Houten ◽  
Jean-Sébastien Annicotte ◽  
Carmen Argmann ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Dietary Lipids ◽  
The Body ◽  
Water Soluble ◽  
Lipid Absorption ◽  
Whole Body ◽  
Amino Acid Conjugate ◽  
Acid Conjugate ◽  
Mouse Hepatocytes ◽  
Somatic Mutagenesis

ABSTRACT Bile acids (BAs) are water-soluble end products from cholesterol metabolism and are essential for efficient absorption of dietary lipids. By using targeted somatic mutagenesis of the nuclear receptor liver receptor homolog 1 (LRH-1) in mouse hepatocytes, we demonstrate here that LRH-1 critically regulates the physicochemical properties of BAs. The absence of LRH-1 and subsequent deficiency of Cyp8b1 eliminate the production of cholic acid and its amino acid conjugate taurocholic acid and increase the relative amounts of less amphipathic BA species. Intriguingly, while the expression of Cyp8b1 is almost extinguished in the livers of mice that lack LRH-1, the expression of the rate-limiting enzyme of BA synthesis, i.e., Cyp7a1, remains unchanged. The profound remodeling of the BA composition significantly reduces the efficacy of intestinal absorption of lipids and reuptake of BAs and facilitates the removal of lipids from the body. Our studies unequivocally demonstrate a pivotal role for LRH-1 in determining the composition of BAs, which, in turn has major consequences on whole-body lipid homeostasis.

Bicarbonate kinetics in humans: identification and validation of a three-compartment model

1995 ◽  
Vol 269 (1) ◽  
pp. E183-E192 ◽  
Author(s):  
M. P. Saccomani ◽  
R. C. Bonadonna ◽  
E. Caveggion ◽  
R. A. DeFronzo ◽  
C. Cobelli
Keyword(s):  
Specific Activity ◽  
Model Identification ◽  
Compartment Model ◽  
Central Compartment ◽  
Good Evidence ◽  
The Body ◽  
Endogenous Production ◽  
Three Compartment Model ◽  
Expired Air

A model of bicarbonate kinetics is crucial to a correct interpretation of experiments for measuring oxidation in vivo of carbon-labeled compounds. The aim of this study is to develop a compartmental model of bicarbonate kinetics in humans from tracer data by devoting particular attention to model identification and validation. The data base consisted of impulse-dose studies of 14C-labeled bicarbonate in nine normal subjects. The decay curve of specific activity of CO2 in expired air (saRCO2) was frequently sampled for 4-7 h. In addition, endogenous production of CO2, VCO2, was measured by indirect calorimetry. A model of data, i.e., an exponential model, analysis of decay curves of saRCO2 showed first that three compartments are necessary and sufficient to describe bicarbonate tracer kinetics. Compartmental models were then used as models of system. To correctly describe the input-output configuration, labeled CO2 flux in the expired air, phi RCO2 (= saRCO2.VCO2), has been used as measurement variable in tracer model identification. A mammillary three-compartment model with a respiratory and a nonrespiratory loss has been studied. Whereas there is good evidence that respiratory loss takes place in the central compartment, whether nonrespiratory loss is taking place in the central compartment or in one of the two peripheral compartments is uncertain. Thus three competing tracer models were considered. Using a model-independent analysis of data, based on the body activity variable, to calculate mean residence time in the system, we have been able to validate a specific model structure, i.e., with the two irreversible losses taking place in the central compartment. This validated tracer model was then used to quantitate bicarbonate masses in the system. Because there is uncertainty about where endogenous production enters the system, lower and upper bounds of masses of bicarbonate in the body are derived.

scholarly journals A study of whole-body isotope dilution of [14C]ascorbic acid in guinea-pigs with graded ascorbate intakes

1992 ◽  
Vol 68 (3) ◽  
pp. 717-728 ◽  
Author(s):  
C. J. Bates ◽  
Harumi Tsuchiya ◽  
P. H. Evans
Keyword(s):  
Dietary Intake ◽  
Guinea Pigs ◽  
Specific Activity ◽  
The Body ◽  
Whole Body ◽  
Dietary Intakes ◽  
Radioactive Label ◽  
Wide Range ◽  
Specific Activities ◽  
The Individual

The purpose of the present study was first to assess the extent to which unlabelled ascorbate in the diet of guinea-pigs can exchange with labelled ascorbate within their organs when the dietary intake is varied over a wide range, and second to determine whether the retention of label might be used to assess either the amount of ascorbate intake or its biological availability where these are not known. The retention of [14C]ascorbate in the body and in various organs of guinea-pigs were, therefore, measured following a 13 d period of graded dietary intakes of ascorbate. It was found first, that the amount of label retained in each of the organs, 13 d after the initial dose of labelled ascorbate, was much more closely related to the amount of ascorbate intake after labelling than to the intake (and tissue ascorbate levels) before and at the time of labelling. Second, most of the individual internal organs exhibited a constant relationship between the specific activity at 13 d and the dietary intake, except for brain which was flushed to a smaller extent. Third, in agreement with several previous studies a high proportion of the radioactive label in the tissues was found to be still present in ascorbate. The specific activity of column-purified ascorbate was very similar to the estimated specific activity in the crude extract, which implies that it may be possible to estimate specific activities (or stable isotope enrichments) at certain sites without rigorous isolation procedures. Fourth, the amount of radioactivity appearing in the urine 2 d before killing the animals was correlated with the amount of ascorbate intake and with tissue specific activities, suggesting that intakes (or bioavailability) might be predicted from the patterns of label-appearance in the urine

scholarly journals Mathematical Models for Cholesterol Metabolism and Transport

Processes ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 155
Author(s):  
Fangyuan Zhang ◽  
Brittany Macshane ◽  
Ryan Searcy ◽  
Zuyi Huang
Keyword(s):  
Mathematical Models ◽  
Drug Targets ◽  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
The Body ◽  
Cholesterol Homeostasis ◽  
Whole Body ◽  
Entire Body ◽  
High Cholesterol ◽  
Cholesterol Levels

Cholesterol is an essential component of eukaryotic cellular membranes. It is also an important precursor for making other molecules needed by the body. Cholesterol homeostasis plays an essential role in human health. Having high cholesterol can increase the chances of getting heart disease. As a result of the risks associated with high cholesterol, it is imperative that studies are conducted to determine the best course of action to reduce whole body cholesterol levels. Mathematical models can provide direction on this. By examining existing models, the suitable reactions or processes for drug targeting to lower whole-body cholesterol can be determined. This paper examines existing models in the literature that, in total, cover most of the processes involving cholesterol metabolism and transport, including: the absorption of cholesterol in the intestine; the cholesterol biosynthesis in the liver; the storage and transport of cholesterol between the intestine, the liver, blood vessels, and peripheral cells. The findings presented in these models will be discussed for potential combination to form a comprehensive model of cholesterol within the entire body, which is then taken as an in-silico patient for identifying drug targets, screening drugs, and designing intervention strategies to regulate cholesterol levels in the human body.

scholarly journals Coexistence of Hashimoto's thyroiditis and papillary thyroidal carcinoma with papillary carcinoma of thyreoglossal duct

2007 ◽  
Vol 64 (10) ◽  
pp. 714-718
Author(s):  
Milica Cizmic ◽  
Mile Ignjatovic ◽  
Snezana Cerovic ◽  
Boris Ajdinovic
Keyword(s):  
Thyroid Gland ◽  
Papillary Carcinoma ◽  
Hashimoto’S Thyroiditis ◽  
Clinical Investigation ◽  
The Body ◽  
Whole Body ◽  
Hashimoto's Thyroiditis ◽  
Thyroglossal Duct ◽  
Right Lobe ◽  
The Right

Background. Simultaneous presence of Hashimoto's thyroiditis and papillary thyroidal carcinoma in thyroidal gland with papillary carcinoma association in thyroglossal duct is quite rare. The questions like where the original site of primary process, is where metastasis is, what the cause of coexisting of these diseasesis present a diagnostic dilemma. Case report. We presented a case of a 53-year old female patient, with the diagnosis of Hashimoto's thyroiditis and symptoms of subclinical hypothyreosis and nodal changes in the right lobe of thyroidal gland, according to clinical investigation. Morphological examination of thyroidal gland, ultrasound examination and scintigraphy with technetium (Tc) confirmed the existence of nonhomogenic tissue with parenchyma nodular changes in the right lobe of thyroidal gland that weakly bonded Tc. Fine needle biopsy in nodal changes, with cytological analyses showed no evidence of atypical thyreocites. Hashimoto's thyroiditis was confirmed on the basis of the increased values of anti-microsomal antibodies, the high levels of thyreogobulin 117 ng/ml and TSH 6.29 ?IU/ml. The operation near by the nodular change in the right lobe of thyroidal gland revealed pyramidal lobe spread in the thyroglossal duct. Total thyroidectomia was done with the elimination of thyroglossal duct. Final patohystological findings showed papillary carcinoma in the nodal changes pT2, N0 and in the thyroglossal duct with the presence of Hashimoto's thyroiditis in the residual parenchyme of the thyroid gland. After the surgery the whole body scintigraphy with iodine 131 (131I) did not reveal accumulation of 131I in the body, while the fixation in the neck was 1%. After that, the patient was treated with thyroxin with suppressionsubstitution doses. Conclusion. Abnormality in embrional development of thyroidal tissue might be the source of thyroidal carcinoma or the way of spreading of metastasis of primary thyroidal carcinoma from thyroid gland. The cause of this process is most probably a hereditary mutation in RET oncogenes.

Effect of Cortisone on Lipid Metabolism of Plasma, Liver and Aorta and on Retrogression of Atherosclerosis in the Rabbit

1956 ◽  
Vol 187 (1) ◽  
pp. 66-74 ◽  
Author(s):  
Abraham Dury
Keyword(s):  
Cholesterol Metabolism ◽  
Specific Activity ◽  
Plasma Cholesterol ◽  
Plasma Lipid ◽  
Plasma Phospholipid ◽  
Phospholipid Metabolism ◽  
Metabolic Effects ◽  
High Cholesterol Diet ◽  
High Cholesterol ◽  
Lipid Distribution

This study was made to assess the relative metabolic effects of cortisone in rabbits on a normal or high cholesterol diet. Cortisone was administered daily for 14 days to normal and atherosclerotic rabbits. Determinations were made of lipid distribution and phospholipid metabolism of plasma, liver and aorta of these groups compared with that of untreated, normal and cholesterol-fed animals. Aortas were examined and judged for severity of atherosclerosis. The most notable effects of administered cortisone on lipid distribution were the extent of mobilized neutral fat to the liver and the elevated level in the plasma. Cholesterol metabolism appeared to be differently affected by cortisone administration to animals on the two types of diet; in cholesterol-fed rabbits the plasma ester cholesterol was significantly depressed while in normal animals cortisone appeared to have promoted a hypercholesterolemia. Plasma lipid interrelationships of cholesterol-fed, cortisone injected rabbits were more like normal and different from that of untreated, atherosclerotic rabbits. The radioactivity data showed that plasma phospholipid turnover rate was increased while specific activity of aortic phospholipid was decreased in rabbits administered cortisone compared with that of the untreated groups. The Sf 12–400 classes of serum lipoproteins were increased in amount in normal and cholesterol-fed rabbits subsequent to administered cortisone. The metabolic findings are discussed with regard to their association with a marked degree of retrogression of the severity of atherosclerosis observed in the cortisone-treated rabbits.

Glucose metabolism and bicarbonate turnover in dystrophic mice

1964 ◽  
Vol 207 (5) ◽  
pp. 1161-1165 ◽  
Author(s):  
Nome Baker ◽  
Robert Huebotter
Keyword(s):  
Specific Activity ◽  
Mean Value ◽  
Relative Increase ◽  
The Body ◽  
Whole Body ◽  
Littermate Control ◽  
Unit Body Weight ◽  
Total Glucose ◽  
Enzymatic Pathways ◽  
Dystrophic Mice

Hereditarily dystrophic and littermate control mice of the Bar Harbor strain 129 were injected with bicarbonate-C14 to compare rates of turnover of the body bicarbonate compartments. A separate group of dystrophic mice was also injected with glucose-U-C14 to study the turnover and oxidation to CO2 of body glucose. The total glucose pool size was also measured in four dystrophic mice and was found to be 50% greater per unit body weight than that of the previously published mean value for control mice. Since the plasma glucose concentration was the same in both groups, the increased glucose compartment size appears to reflect a relative increase in extracellular space. Specific activity-time curves of respiratory C14O2 were identical in both groups of mice after intravenous injection of bicarbonate-C14. Average values of plasma and whole body glucose specific activity 5–15 min after injection of glucose were lower than, but not significantly different from, those reported previously for control mice. The rate of formation of C14O2 from glucose-C14 was at least as fast in dystrophic mice as in controls. The data indicate that the enzymatic pathways involved in glycolysis, the citric acid cycle, glucogenesis, and gluconeogenesis are functionally active in this disease.

Salinity-induced Changes in Branchial Na+/K+- ATPase Activity and Transepithelial Potential Difference in the Brine Shrimp Artemia Sauna

1990 ◽  
Vol 151 (1) ◽  
pp. 279-296 ◽  
Author(s):  
CHARLES W. HOLLIDAY ◽  
DAVID B. ROYE ◽  
ROBERT D. ROER
Keyword(s):  
Brine Shrimp ◽  
Sea Water ◽  
Specific Activity ◽  
Silver Ions ◽  
Artemia Salina ◽  
The Body ◽  
Salt Transport ◽  
Whole Body ◽  
Chloride Cells ◽  
Transepithelial Potential

Silver staining of the adult brine shrimp, Artemia salina, revealed that only the metepipodites of the phyllopodia were significantly permeable to chloride and/or silver ions. The metepipodites stained in a reticulated pattern, possibly indicating areas in the cuticle over cells specialized for chloride secretion. Crude homogenates of metepipodites had very high Na+/K+-ATPase enzyme specific activity (ESA) which increased in proportion to the salinity of the external medium and, thus, in proportion to the need for outward salt transport in these strongly hypoosmoregulating animals. Metepipodite ESA as a percentage of whole-body ESA increased from 7.6% in 50% sea water (SW) to 25.0% in 400%SW. Gut and maxillary gland also had high Na+/K+-ATPase ESAs, implicating these organs in osmoregulatory processes as well. The time courses of increases in phyllopodial and gut ESAs in brine shrimps transferred from 100% SW to 400 % SW are consistent with the induction of new Na+/K+-ATPase; 4–7 days was required for significant increases to occur. Haemolymph ion analyses and transepithelial potential differences, measured in brine shrimp acclimated in all the SW media, indicate that chloride is actively transported out of the brine shrimp while sodium is very close to electrochemical equilibrium across the body wall. Thus, the metepipodites of the brine shrimp appear to possess cells with many functional similarities to the teleost branchial chloride cells.

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