Extravascular Albumin Mass and Exchange in Rat Tissues

1970 ◽  
Vol 39 (6) ◽  
pp. 705-724 ◽  
Author(s):  
J. Katz ◽  
G. Bonorris ◽  
Sybil Golden ◽  
A. L. Sellers
Keyword(s):  
Body Weight ◽  
Ascitic Fluid ◽  
Specific Activity ◽  
The Body ◽  
Rat Tissues ◽  
Extracellular Water ◽  
Tissue Extracts ◽  
Albumin Content ◽  
Multicompartmental Analysis ◽  
Specific Activities

1. Extravascular albumin in carcass, skin and gut of rats was extracted and the albumin content estimated by several methods. Assay by electrophoresis on acrylamide gel, by immunodiffusion and by radioimmunoassay were in essential agreement. The method used previously, precipitation with antibody followed by alcohol-TCA extraction, underestimates the amount of albumin in tissue extracts, because extraction from the antibody precipitate is not complete. This method is valid, however, for specific activity determination. 2. Normal rats contain from 500 to 650 mg of albumin per 100 g body weight. Of this, 20–25% is in the circulation, 35–40% in the carcass (mainly but not exclusively muscle), 20–25% in skin and 10% in gut. 3. The extracellular water of muscle, carcass, skin and gut was estimated from the distribution of mannitol and sulphate. With the exception of gut, both methods agreed closely. Extracellular, extravascular water constitutes about 23% of the body weight of 150–200 g rats. The extracellular water in muscle is about 20% and in skin, 40%. In gut the extracellular water cannot be estimated reliably by these compounds. 4. Muscle contains about 3·5 mg/g of extravascular albumin; skin and gut, 7–8 mg/g. The concentration of extravascular albumin in extracellular water of muscle and skin is 1620 mg/ml, or 5060% of the concentration in plasma. In the small intestine the concentration of albumin is higher, possibly similar to that in plasma. 5. In rats with severe aminonucleoside nephrosis, body albumin was depleted to 100–200 mg/100 g. Of this, 15–25% was in plasma, 50% in carcass, and about 15% in skin. Ascitic fluid contained only a few mg of albumin. 6. The specific activity of extravascular albumin of tissues was followed after intravascular injection of 125I- or 131I-labelled albumin. The specific activity of carcass albumin increases rapidly, becoming equal to that in plasma after less than 2 days. The specific activity of albumin in skin increases much more slowly and becomes equal to that of plasma after 4 days. Labelling of albumin of gut is even slower. The specific activities in tissue never exceed that in plasma. 7. In severely nephrotic rats, specific activities in carcass and skin become equal to that in plasma within 2–3 days and remain equal thereafter. Specific activity of albumin in ascitic fluid increases to reach values as much as sixteen-fold those in plasma. 8. The extravascular pool, as calculated by multicompartmental analysis from the slopes and intercepts of the plasma curve, is about equal to that in plasma and in severely nephrotic rats is less than that in plasma. Discrepancies between calculated and observed extravascular albumin masses is by a factor of 3 in normal rats and 10 or more in severely nephrotic rats. 9. Specific activity of extravascular albumin as calculated from multicompartmental analysis is 1·5 times that in plasma in normal rats and at least six times that in plasma in severely nephrotic rats. Actually, the specific activities in extravascular and vascular albumin ultimately become and remain equal. 10. It is concluded that the multicompartmental model of vascular pool exchange with one or two extravascular pools is not valid for rats and probably not for other animal species.

Unequal Absorption of Radiolabeled and Nonradiolabeled Drug from the Oral Dose Leads to Incorrect Estimates of Drug Absorption and Circulating Metabolites in a Mass Balance Study

2019 ◽  
Vol 13 (1) ◽  
pp. 37-44
Author(s):  
Ryan H. Takahashi ◽  
Jae H. Chang ◽  
Jodie Pang ◽  
Xiaorong Liang ◽  
Shuguang Ma
Keyword(s):  
Oral Dose ◽  
Mass Balance ◽  
Specific Activity ◽  
The Body ◽  
Total Drug ◽  
Beagle Dogs ◽  
Balance Study ◽  
Drug Concentrations ◽  
Specific Activities ◽  
Mass Balance Study

Background: Mass balance studies conducted using radiolabeled material (14C or 3H) definitively characterize the Absorption, Metabolism, and Excretion (AME) of a drug. A critical aspect of these studies is that the radiotracer maintains its proportion to total drug from its administration to its complete elimination from the body. In the study of GDC-0276 in beagle dogs, we observed that the 14C radiotracer proportion (specific activity) varied through the study. Method: High resolution-accurate mass spectrometric measurements of 12C and 14C isotopes of GDC- 0276 and its metabolites in plasma and excreta samples were used to determine the apparent specific activities, which were higher than the specific activity of the dosing formulation. Drug concentrations were adjusted to the observed specific activities to correct the readouts for GDC-0276 AME and PK. Results: The enrichment of 14C, which resulted in higher specific activities, was consistent with faster and more extensive absorption of the radiotracer from the dosing formulation. This resulted in overestimating the dose absorbed, the extent of elimination in urine and bile, and the exposures to circulating metabolites. These biases were corrected by the specific activities determined for study samples by mass spectrometry. Conclusion: Assuming that the radiotracer was proportional to total drug throughout a radiolabeled study was not valid in a 14C study in beagle dogs. This presumably resulted from unequal absorption of the radiotracer and nonradiolabeled test articles from the oral dose due to inequivalent solid forms. We were able to provide a more accurate description of the AME of GDC-0276 in dogs by characterizing the differential absorption of the radiotracer.

scholarly journals FURTHER STUDIES ON EFFECTS OF TISSUE EXTRACTS ON STAPHYLOCOCCUS AUREUS

1946 ◽  
Vol 84 (3) ◽  
pp. 247-261 ◽  
Author(s):  
Leo G. Nutini ◽  
Sister Eva Maria Lynch
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
The Body ◽  
Brain Extract ◽  
Toxicity Tests ◽  
Control Series ◽  
Experimental Animals ◽  
Tissue Extracts

1. The ability of alcoholic-precipitated extracts of beef tissue—brain, spleen, heart, and kidney—to stimulate the growth of Staphylococcus aureus, in vitro, and to convert the yellow S form to a white R variant with altered biochemical characteristics conforming to those of an avirulent organism, has been confirmed. 2. The avirulence of the white R variant has been established by tests in vivo on mice. 3. Staphylococcus aureus infections induced subcutaneously, intraperitoneally, and intravenously in mice responded favorably to brain extract following subcutaneous or oral administration. The mortality was 2 per cent in 444 experimental animals and 81 per cent in 448 control animals. 4. The extracts appeared equally efficient when used therapeutically (mortality 2 per cent of 162 experimental animals and 90 per cent in the control series) or prophylactically (mortality 2 per cent of 282 experimental animals and 76 per cent in 286 control mice). Extracts of brain and spleen were more effective than those of either heart or kidney. 5. Studies concerning the mechanism of action of the tissue extracts indicate that they prevented the formation of toxin by Staphylococcus aureus, and had but little effect on toxin actions. 6. Toxicity tests revealed that the brain and spleen extracts were relatively non-toxic, dosages equivalent to 2 per cent of the body weight being well tolerated. Kidney and heart extracts were much more toxic, producing mortality in dosages as low as 0.3 per cent of the body weight.

scholarly journals Forms of lipoprotein lipase in rat tissues: in adipose tissue the proportion of inactive lipase increases on fasting

1996 ◽  
Vol 313 (3) ◽  
pp. 893-898 ◽  
Author(s):  
Martin BERGÖ ◽  
Gunilla OLIVECRONA ◽  
Thomas OLIVECRONA
Keyword(s):  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Translational Regulation ◽  
Specific Activity ◽  
Catalytic Efficiency ◽  
Rat Tissues ◽  
Tissue Extracts ◽  
Significant Difference ◽  
Lpl Mass ◽  
Fasted Rats

Previous studies have shown that the ratio of lipoprotein lipase (LPL) catalytic activity to LPL mass in tissues differs in different conditions, but it is not clear whether this occurs by a change in the catalytic efficiency of the LPL molecules, or because of a shift in the relation between active and inactive forms of the enzyme. To explore this, we have measured LPL activity and mass in detergent extracts of rat tissues. LPL specific activity was high and similar in heart, skeletal muscle, lung and brain. The liver had significantly lower specific activity, which is in accord with previous findings that the liver takes up and catabolizes LPL. The specific activity was also low in adipose tissue from fasted rats. When tissue extracts were applied to columns of heparin–agarose and eluted by a gradient of NaCl, a peak of active LPL was eluted at 1.0 M NaCl, but there was also a peak of inactive LPL protein, which was eluted at 0.6 M NaCl. In adipose tissue, LPL activity decreased by 70–80% during an overnight fast, whereas LPL mass decreased by only 20–40%. The mass ratio between inactive and active LPL, as separated by heparin–agarose chromatography, increased from 0.5 to over 2 during the fast. In hearts there was no significant difference between fed and fasted rats in total LPL activity, LPL mass or in the distribution between inactive and active forms. The results indicate that the relation between inactive (probably monomeric) and active (dimeric) forms of LPL is a target for post-translational regulation in adipose tissue.

scholarly journals Polyamine and intestinal properties in adult rats

1996 ◽  
Vol 76 (4) ◽  
pp. 627-637 ◽  
Author(s):  
Patricia Deloyer ◽  
Guy Dandrifosse ◽  
Catherine Bartholomeus ◽  
Nadine Romain ◽  
Monique Klimek ◽  
...  
Keyword(s):  
Body Weight ◽  
Specific Activity ◽  
Experimental Conditions ◽  
Adult Rats ◽  
Distal Intestine ◽  
Germ Free ◽  
Polyamine Content ◽  
Intestinal Functions ◽  
Wet Weight ◽  
Specific Activities

We questioned whether polyamines coming from the diet or produced by intestinal microflora or by intracellular metabolism influence intestinal functions. Therefore, we compared pathogen-free rats and germ-free rats receiving a diet with low polyamine content and either treated or not treated with difluoromethylornithine (DFMO) and/or methylglyoxal bis (guanylhydrazone) (MGBG). Wet weight, protein content, DNA content, sucrase (EC3.2.1.48), maltase (EC 3.2.1.20) and lactase (EC 3.2.1.23) specific activities, amounts of putrescine, spennidine and spemine were measured in the mucosa of the proximal and distal intestine. Body weight was also determined. Rats without microflora had a higher specific activity of maltase and higher amounts of spermidine and spermine but lower lactase specific activity than pathogen-free animals; the low-polyamine diet given to gem-free rats had little effect on the functional variables measured (decrease of maltase and lactase specific activities) and did not modify the amounts of polyamines. DFMO and/or MGBG administered to germ-free rats receiving a low-polyamine diet induced modifications of most of the variables studied. Body weight and wet weight of proximal and distal intestine decreased, disaccharidase specific activities decreased, and amounts of polyamines changed according to the inhibitor used. Thus, our results showed that the deprivation of polyamine supply from microflora or from the diet failed, under our experimental conditions, to affect the intestinal properties analysed but exogenous and endogenous polyamine restriction altered general properties of the organism as well as intestinal functions.

Effect of propylthiouracil-induced hypothyroidism on phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin synthesis in chick liver microsomes

1976 ◽  
Vol 54 (1) ◽  
pp. 15-21 ◽  
Author(s):  
E. M. Lyman ◽  
J. L. Dove ◽  
M. Sribney
Keyword(s):  
Endoplasmic Reticulum ◽  
Body Weight ◽  
Specific Activity ◽  
Liver Microsomes ◽  
Specific Activities ◽  
Low Levels

Biosynthesis of phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin was studied in liver endoplasmic reticulum obtained from newly hatched chicks which were made hypothyroid by feeding 0.2% propylthiouracil.In vitro measurements were made of the specific activities of phosphorylcholine-glyceride (cholinephosphotransferase (EC 2.7.8.2)), phosphorylethanolamine-glyceride (ethanolamine-phosphotransferase (EC 2.7.8.1)), and phosphorylcholine-ceramide (ceramide cholinephosphotransferase (EC 2.7.8.3)) transferases in control and hypothyroid chick liver for a period of 40 days. The specific activity of all three transferases began to decline after the chicks were on the propylthiouracil-containing diet for 5 days and steadily declined, reaching levels 10–15% of the controls after 15 days. These low levels were maintained for as long as the chicks were on this diet.Administration of L-thyroxine (15 μg/100 g of body weight) to the hypothyroid chicks caused a marked increase in the specific activities of all three transferases, reaching levels similar to those seen in the control chicks in 36–48 h. The specific activities then declined as the chicks were maintained on the diet of propylthiouracil, reaching the former low levels after 120 h.Administration of cycloheximide alone to the hypothyroid chicks caused a rise in the specific activities of the transferases after 24 h approximately equal to that caused by thyroxine alone, while thyroxine and cycloheximide together were no different than either alone.These studies indicate that in some manner circulating thyroxine controls the activities of enzymes involved in the biosynthesis of phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin in chick liver endoplasmic reticulum. There was no evidence that induction of hypothyroidism by propylthiouracil had any effect on the activities of these enzymes in the CNS.

Maternal dietary deficiency and its effect on the metabolism of nucleic acids and proteins. "Effect of exchanging the young, during the lactation period, between the control and undernourished female rats"

1978 ◽  
Vol 56 (2) ◽  
pp. 274-286 ◽  
Author(s):  
Tapas Goswami ◽  
Uma Srivastava
Keyword(s):  
Nucleic Acids ◽  
Protein Content ◽  
Specific Activity ◽  
The Body ◽  
Female Rats ◽  
Control Group ◽  
Lactation Period ◽  
Specific Activities ◽  
The Brain ◽  
Dietary Deficiency

The effect of maternal dietary deficiency on the metabolism of nucleic acids and proteins was studied by exchanging the pups of control and undernourished dams during the lactation period. In the pups of control dams fostered by undernourished dams during the lactation period (E3), it was observed that the body and organ weight, and RNA, DNA, and protein content failed to increase normally. Contrary to this, the free leucine and nucleotide contents were higher and their specific activities lower in the plasma and various organs of the E3 group as compared with the control group.Specific activity of protein was higher in the liver, brain, kidney, and lung, and was lower in the spleen and heart of the E3 group as compared with the control group. Specific activity of RNA was higher in the liver, spleen, and lung, and was lower in the brain, kidney, and heart of the E3 group as compared with the control group.In the pups of undernourished dams fostered by the control dams during the lactation period (E1), the body and organ weights, the RNA, DNA, and protein content, the content of free leucine and nucleotides as well as their specific activities, and the specific activity of protein and RNA were partially or completely restored. However, the DNA content of the brain remained unchanged in comparison with those pups of undernourished dams nursed by their own mother (E2). In the brain, kidney, spleen, and lung of the E1 group, the specific activity of RNA increased considerably and even exceeded the control values.The radioactivity results discussed above clearly demonstrate an accelerated metabolism of protein and RNA in the various organs of the E3 group and a partial or complete normalization in the E1 group.

THE VALIDITY OF THE CALCULATION OF SECRETION RATES FROM THE SPECIFIC ACTIVITY OF A URINARY METABOLITE

1961 ◽  
Vol 36 (2) ◽  
pp. 265-280 ◽  
Author(s):  
K. R. Laumas ◽  
J. F.. Tait ◽  
S. A. S. Tait
Keyword(s):  
Continuous Infusion ◽  
Experimental Test ◽  
Specific Activity ◽  
Single Injection ◽  
Hormone Secretion ◽  
The Body ◽  
The Other ◽  
Urinary Metabolite ◽  
Specific Activities ◽  
Secretion Rates

ABSTRACT The validity of the calculation of secretion rates from the specific activity of a urinary metabolite after the injection of the radioactive hormone (secretion rate equals radioactivity injected divided by the specific activity of a urinary metabolite ) has been critically examined. Although in previous applications of the method the expression has been assumed to be valid on an intuitive basis, it is concluded that this is not justified unless after continuous infusion the specific activity of the hormone is constant throughout the body. In the case of a single injection, where W has been termed the single injection factor, and must be equal to one for the method to be valid. If the transport and metabolism of the hormone can be described in terms of an outer and inner pool, it has been shown that the single injection factor is nearly equal to one unless the metabolite which is analyzed is formed mostly in one pool but the overall metabolism largely occurs in the other space. Other assumptions and sources of error in the method are discussed. It is concluded that a comparison of the specific activities of various metabolites is the most generally applicable experimental test of the validity of the method. On this basis, applications of the method to obtain the secretion rates of aldosterone and cortisol seem to be justified.

BODY WATER OF NEWBORN INFANTS OF DIABETIC MOTHERS

1960 ◽  
Vol XXXIV (II) ◽  
pp. 261-276 ◽  
Author(s):  
Mogens Osler
Keyword(s):  
Body Weight ◽  
Water Content ◽  
Total Body Water ◽  
Newborn Infants ◽  
Body Water ◽  
The Body ◽  
Intracellular Water ◽  
Extracellular Water ◽  
Total Body ◽  
Diabetic Mothers

ABSTRACT The total body water as well as the distribution of water in the extracellular and intracellular compartments was determined in 23 infants born to diabetic mothers (diab. infants) and 15 infants born to normal mothers (normal infants). The total body water was determined by the dilution method using heavy water, and the extracellular water by the dilution method using thiosulphate. Intracellular water was calculated as total water less extracellular water. The analytical methods are described. Diab. infants proved to have a mean total body water of 2.48 litres or 70.2 per cent of the body weight, a mean extracellular water content of 1.41 litre or 38.5 per cent of the body weight, and a mean intracellular water content of 1.16 litre or 31.8 per cent of the body weight. Normal infants had a mean total body water of 2.58 litres or 78.2 per cent of the body weight, a mean extracellular water content of 1.53 litre or 44.9 per cent of the body weight, and a mean intracellular water content of 1.12 litre or 33.5 per cent of the body weight. The reduction in total and extracellular water in the diab. infants is statistically significant, whereas that of intracellular water is more doubtful. The reduction in total body water means that diab. infants are obese. A marked decrease in total as well as extracellular water without a substantial decrease in intracellular water cannot be due to obesity alone, since fat is assumed to contain more extracellular than intracellular water. Increased deposition of glycogen, which binds water in the cells and constitutes an intermediate product in the transformation of glucose to fat, can explain, when also considering the obesity, the reduction in total and extracellular water without a simultaneous decrease of intracellular water. Considering the influence of insulin, corticosteroids and growth hormone on the body composition, the author concludes that the changes found in the body composition of newborn infants of diabetic mothers (obesity + presumably increased glycogen) may be assumed to be due to maternal hyperglycaemia with consequent foetal hyperglycaemia + hyperinsulinism, but not to an action of maternal growth hormone. In other words, the result supports the so-called hyperglycaemia hypothesis as the cause of the increased weight and changed body composition of the newborn infants of diabetic women.

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

BODY WATER COMPOSITION IN KWASHIORKOR BEFORE AND AFTER LOSS OF EDEMA

PEDIATRICS ◽  
1965 ◽  
Vol 36 (1) ◽  
pp. 94-103
Author(s):  
Gail Lynn Brinkman ◽  
Malcolm David Bowie ◽  
Bent Friis-Hansen ◽  
John Derek Lindsell Hansen
Keyword(s):  
Body Weight ◽  
Sodium Thiosulfate ◽  
Body Water ◽  
The Body ◽  
Extracellular Water ◽  
Water Composition ◽  
Before And After ◽  
Per Se ◽  
Body Compartments ◽  
Total Body

1. Total body water (TBW) estimated by tritium and extracellular water (ECW) estimated by sodium thiosulfate has been measured in 19 cases of kwashiorkor before and immediately after loss of edema. 2. The TBW as a percentage of body weight was increased but changed relatively little as edema was lost (70%-69%). 3. The ECW (thiosulfate space) showed a significant decrease with loss of edema (33%-26%). 4. The intracellular water (TBW-ECW) increased markedly (37%-43%). 5. These results suggest that the edema of kwashiorkor is a phenomenon of mal-distribution of the excess body water between the body compartments and not only an excess accumulation of body water per se.

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