Effect of Nephrectomy and Enterectomy on Plasma Clearance of Intravenously Administered Dipeptides in Rats

1977 ◽  
Vol 52 (2) ◽  
pp. 205-213 ◽  
Author(s):  
S. A. Adibi ◽  
B. A. Krzysik
Keyword(s):  
Small Intestine ◽  
Renal Clearance ◽  
Intestinal Mucosa ◽  
Half Life ◽  
Plasma Clearance ◽  
Renal Cortex ◽  
Plasma Concentrations ◽  
Remarkable Effect ◽  
Body Tissues ◽  
Plasma Half Life

1. Sham-operated and bilaterally nephrectomized rats were injected intravenously with glycyl-l-leucine, glycylglycine and glycylsarcosine, and the concentrations of these dipeptides in plasma and muscle, liver, renal cortex (in the sham-operated rats) and intestinal mucosa at various intervals were determined. 2. Initially the plasma concentrations of glycyl-leucine and glycylglycine were higher in nephrectomized than in control rats but later the concentrations were similar in both groups of rats. The disappearance of these two dipeptides from plasma was almost complete within 20 min, and their plasma half-lives were not changed remarkably by nephrectomy. In contrast, nephrectomy markedly impaired disappearance of glycylsarcosine from plasma and prolonged its half-life from 7·6 min to 52·0 min. 3. Glycyl-leucine and glycylglycine were not detected in tissues of control rats injected with these dipeptides, but glycylsarcosine was recovered from all four tissues examined. Nephrectomy resulted in greater accumulations of glycylsarcosine in tissues and the appearance of glycylglycine in the remaining three tissues and glycyl-leucine in muscle. 4. Enterectomy did not have a remarkable effect on plasma half-life of glycylglycine but it allowed recovery of this dipeptide from renal cortex, liver and muscle. 5. It is concluded that kidneys and small intestine are involved in the disposition of circulating dipeptides, but in their absence other tissues may assume a greater role in this regard. However, renal clearance appears to be an important route for the disposition of dipeptides which are poorly hydrolysed by body tissues.

Metabolism of Intravenously Administered Dipeptides in Rats: Effects on Amino Acid Pools, Glucose Concentration and Insulin and Glucagon Secretion

1977 ◽  
Vol 52 (2) ◽  
pp. 193-204 ◽  
Author(s):  
S. A. Adibi ◽  
B. A. Krzysik ◽  
A. L. Drash
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Intestinal Mucosa ◽  
Intravenous Administration ◽  
Free Amino Acids ◽  
Free Amino ◽  
Renal Cortex ◽  
Plasma Concentrations ◽  
Acid Mixture ◽  
Body Tissues

1. Studies were performed to investigate the metabolic fate of dipeptides when administered intravenously in rats. Glycyl-leucine, glycylglycine or glycylsarcosine was injected into the jugular vein. The plasma disappearance rate after the peak plasma concentrations was most rapid for glycyl-leucine and least rapid for glycylsarcosine. 2. During urine collection for 40 min, trace amounts of glycyl-leucine and glycylglycine and 13% of the injected glycylsarcosine were excreted. 3. Neither glycylglycine nor glycyl-leucine was detected in the liver, muscle, intestinal mucosa or renal cortex, but concentrations of glycine or leucine, or both, in these tissues were increased after each injection. In contrast, glycylsarcosine was recovered in all these tissues with concentrations in the renal cortex being far greater than in any other tissue, but sarcosine was found only in the renal cortex and intestinal mucosa. 4. The changes in plasma concentrations of free amino acids, glucose and glucagon, and tissue concentrations of free amino acids, were similar after the intravenous administration of glycyl-leucine and an equimolar mixture of free glycine and leucine. However, the amount of insulin secreted during the 40 min after glycyl-leucine injection was 1·6 times that produced after the injection of the corresponding amino acid mixture. 5. Results show that, within the present experimental conditions, the intravenous administration of dipeptides is as effective as that of the corresponding free amino acids in enriching the tissue pools of amino acids. It is suggested that efficient hydrolysis by cellular enzymes prohibits accumulation of intact dipeptides in body tissues.

Increased Clearance Explains the Ultra-Large Multimers in Von Willebrand Disease Type 2M Vicenza; Lessons from Recombinant VWF Vicenza and Modeling of Multimer Catabolism.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3669-3669 ◽  
Author(s):  
András Gézsi ◽  
Gábor Balázsi ◽  
Krisztina Sallai ◽  
Adrienn Mohl ◽  
Eszter Nagy ◽  
...  
Keyword(s):  
Half Life ◽  
Time Course ◽  
Plasma Concentrations ◽  
Von Willebrand Disease ◽  
Published Data ◽  
Primary Defect ◽  
Fixed Rate ◽  
Normal Platelet ◽  
Von Willebrand ◽  
Plasma Half Life

Abstract The pathogenesis of VWD Vicenza has remained elusive. VWD Vicenza is characterized by low plasma but normal platelet VWF concentration, the presence of ultra-large plasma multimers, and a heterozygous R1205H mutation. VWF Vicenza is reported to have a decreased half-life in the circulation. When we expressed rVWF Vicenza R1205H in 293T cells, it was secreted with wild type efficiency and multimer distribution, suggesting that the primary defect is accelerated clearance. To evaluate this hypothesis, we developed a pharmacokinetic model of VWF multimer catabolism. The initial assumptions are: 1. Secretion occurs at a fixed rate with the initial “ultra-large” multimer distribution seen in platelet alpha granules. 2. Cleavage of multimers occurs with a probability p that increases with increasing multimer size. 3. Clearance occurs with a time constant determined by the plasma half life and is independent of multimer size. Modeled multimer distributions were compared to those determined experimentally for patient plasma samples. The effects of DDAVP infusion also were modeled and compared to published data (Casonato et al, Blood2002; 99:180). For p = 7.5 x 10−4 min−1 and a half life of 12 h, the modeled multimer patterns were comparable to the observed steady-state distribution of normal VWF. Decreasing the half life to 2 hours produces a low plasma concentration of “ultra-large” multimers typical of VWD Vicenza without a change in any other parameter. Conversely, increasing the probability of cleavage by only thirty percent produces typical VWD 2A multimer distributions. The model also reproduces the triplet patterns of normal and type 2A VWF. Finally, the DDAVP simulations reproduced the time course of VWF plasma concentrations and multimer distributions of DDAVP-treated patients. We conclude that increased clearance alone can explain the ultra-large multimer distribution of VWD Vicenza. Similar modeling should allow the estimation of VWF cleavage and clearance rates in other variants of VWD and in other clinical situations including thrombotic thrombocytopenic purpura. Figure Figure Figure Figure

Escherichia coli enterotoxin receptors: localization in opossum kidney, intestine, and testis

1989 ◽  
Vol 257 (5) ◽  
pp. F874-F881 ◽  
Author(s):  
L. R. Forte ◽  
W. J. Krause ◽  
R. H. Freeman
Keyword(s):  
Escherichia Coli ◽  
Small Intestine ◽  
Intestinal Mucosa ◽  
Renal Cortex ◽  
Proximal Tubules ◽  
Kidney Cortex ◽  
Seminiferous Tubules ◽  
Small Intestinal Mucosa ◽  
Opossum Kidney ◽  
E Coli

The distribution of receptors for Escherichia coli enterotoxin were examined in opossum kidney, intestine, and testis. E. coli enterotoxin stimulated guanosine 3',5'-cyclic monophosphate (cGMP) production in renal cortex, testis, and small intestinal mucosa but had only a small effect in the colon. Atrial natriuretic factor enhanced the cGMP content of renal cortex and small intestine but had no effect on testis or colon. The enterotoxin receptors were observed to be localized in proximal tubules, to epithelial cells of crypts and villi of small intestine, to crypts of colon, and in seminiferous tubules. Both convoluted and straight portions of proximal tubules exhibited specific binding sites for 125I-labeled enterotoxin. Glomeruli and distal tubules did not have receptors. Binding of 125I-enterotoxin to brush-border membranes of kidney cortex or intestinal mucosa and to testis membranes was markedly temperature dependent. The binding affinities of these receptors for E. coli enterotoxin were similar (i.e., IC50 approximately equal to 0.4-0.5 nM). Daily administration of 20 micrograms of enterotoxin intramuscularly to opossums increased urine cGMP excretion with no apparent changes in urine volume, Na+, or K+ excretion. Thus receptors for heat-stable enterotoxins are localized to proximal tubules of kidney and to enterocytes and seminiferous tubules of intestine and testis, respectively. Apical membranes may be the site of enterotoxin receptors in these epithelia.

Absorption and Excretion of 17, 21-Dihydroxy-20-Ketosteroids in Dogs

1956 ◽  
Vol 2 (3) ◽  
pp. 170-174 ◽  
Author(s):  
Robert H Silber ◽  
Evan R Morgan
Keyword(s):  
Double Bond ◽  
Urinary Excretion ◽  
Intravenous Administration ◽  
Half Life ◽  
Parent Compound ◽  
Plasma Concentrations ◽  
Plasma Half Life

Abstract The plasma concentrations of free 17,21-dihydroxy-20-ketosteroids and urinary excretion of both free and glucuronide forms have been determined after oral, intramuscular, and intravenous administration of cortisone, hydrocortisone, their δ1 forms, and 9α-fluorohydrocortisone to dogs. Excretion of the glucuronide forms of those steroids with a double bond at the 1-2 position or with a fluorine at position 9 was depressed, and the plasma half-life of each of these steroids was longer than that of the parent compound.

Plasma Concentrations of Isoniazid in Children with Tuberculous Infections

PEDIATRICS ◽  
1981 ◽  
Vol 67 (6) ◽  
pp. 876-878
Author(s):  
William A. Olson ◽  
Albert W. Pruitt ◽  
Peter G. Dayton
Keyword(s):  
Half Life ◽  
Plasma Concentrations ◽  
Tuberculous Infection ◽  
Intramuscular Route ◽  
Routes Of Administration ◽  
Plasma Half Life

Six children with tuberculous infection were given their daily prescribed doses of isoniazid by the oral and the intramuscular route on different days. The plasma concentrations reached after both routes of administration were nearly equivalent. The plasma half-life of isoniazid ranged from 1.6 to 4.8 hours. The observed plasma concentrations in these children were higher than those reported in many adults. This difference is due to the larger doses of isoniazid prescribed for children.

scholarly journals Stereospecific Analysis and Enantiomeric Disposition of 3,4-Methylenedioxymethamphetamine (Ecstasy) in Humans

1999 ◽  
Vol 45 (7) ◽  
pp. 1058-1069 ◽  
Author(s):  
John K Fallon ◽  
Andrew T Kicman ◽  
John A Henry ◽  
Peter J Milligan ◽  
David A Cowan ◽  
...  
Keyword(s):  
Gas Chromatography ◽  
Half Life ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Stereospecific Analysis ◽  
Enantiomeric Composition ◽  
Gas Chromatography Mass Spectrometry ◽  
Recovered Material ◽  
Plasma Half Life

Abstract Background: Little is known concerning the enantioselective disposition of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) in humans. In addition, the potential of utilizing the stereochemical composition of an analyte in biological media for forensic purposes requires investigation. Methods: The enantiomers of MDMA and its demethylated metabolite, 3,4-methylenedioxyamphetamine (MDA), present in plasma and urine extracts were derivatized with (−)-(R)-α-methoxy-α-trifluoromethylphenylacetyl chloride and analyzed by gas chromatography–mass spectrometry and gas chromatography, respectively. The enantioselective disposition of MDMA and MDA was determined following oral administration of racemic MDMA (40 mg) to eight male volunteers. Results: The plasma concentrations of (R)-MDMA exceeded those of the S-enantiomer [ratio R:S of the area under the curve (AUC), 2.4 ± 0.3], and the plasma half-life of (R)-MDMA (5.8 ± 2.2 h) was significantly longer than that of the S-enantiomer (3.6 ± 0.9 h). The majority of the recovered material in urine was excreted within 24 h after dosing, with the recovery of (R)-MDMA (21.4% ± 11.6%) being significantly greater than that of (S)-MDMA (9.3% ± 4.9%), and with (S)- and (R)-MDA accounting for 1.4% ± 0.5% and 1.0% ± 0.3% of the dose, respectively. Mathematical modeling of plasma enantiomeric composition vs sampling time demonstrated the applicability of using stereochemical data for the prediction of time elapsed after drug administration. Conclusions: Analytical methods for determining the enantiomeric composition of MDMA and MDA in plasma and urine were developed. The disposition of MDMA in humans is stereoselective, with the more active S-enantiomer having a reduced AUC and shorter half-life than (R)-MDMA. The determination of stereochemical composition may be applicable for forensic purposes.

scholarly journals Apolipoprotein C-II Mimetic Peptide Promotes the Plasma Clearance of Triglyceride-Rich Lipid Emulsion and the Incorporation of Fatty Acids into Peripheral Tissues of Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Tomohiro Komatsu ◽  
Toshihiro Sakurai ◽  
Anna Wolska ◽  
Marcelo J. Amar ◽  
Akiko Sakurai ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Half Life ◽  
Lipid Emulsion ◽  
Plasma Clearance ◽  
Mutant Mice ◽  
Lipid Emulsions ◽  
Peripheral Tissues ◽  
Apolipoprotein C ◽  
Tissue Incorporation ◽  
Plasma Half Life

Aim. Plasma apolipoprotein C-II (apoC-II) activates lipoprotein lipase (LPL) and thus lowers plasma triglycerides (TG). We previously reported that a human apoC-II mimetic peptide (C-II-a) decreased plasma TG in apoC-II mutant mice, as well as in apoE-knockout mice. Because it is unknown what tissues take up free fatty acids (FFAs) released from TG after C-II-a peptide administration, we investigated in mice TG plasma clearance and tissue incorporation, using 3H-triolein as a tracer, with and without C-II-a treatment. Methods and Results. Intralipid® fat emulsion was labeled with 3H-triolein and then mixed with or without C-II-a. Addition of the peptide did not alter mean particle size of the lipid emulsion particles (298 nm) but accelerated their plasma clearance. After intravenous injection into C57BL/6N mice, the plasma half-life of the 3H-triolein for control and C-II-a treated emulsions was 18.3 ± 2.2 min and 14.8 ± 0.1 min, respectively. In apoC-II mutant mice, the plasma half-life of 3H-triolein for injected control and C-II-a treated emulsions was 30.1 ± 0.1 min and 14.8 ± 0.1 min, respectively. C57BL/6N and apoC-II mutant mice at 120 minutes after the injection showed increased tissue incorporation of radioactivity in white adipose tissue when C-II-a treated emulsion was used. Higher radiolabeled uptake of lipids from C-II-a treated emulsion was also observed in the skeletal muscle of C57BL/6N mice only. In case of apoC-II mutant mice, decreased uptake of radioactive lipids was observed in the liver and kidney after addition of C-II-a to the lipid emulsion. Conclusions. C-II-a peptide promotes the plasma clearance of TG-rich lipid emulsions in wild type and apoC-II mutant mice and promotes the incorporation of fatty acids from TG in the lipid emulsions into specific peripheral tissues.

Plasma Thrombospondin as an Indicator of Intravascular Platelet Activation in Patients with Vasculitis

1987 ◽  
Vol 58 (03) ◽  
pp. 850-852 ◽  
Author(s):  
M B McCrohan ◽  
S W Huang ◽  
J W Sleasman ◽  
P A Klein ◽  
K J Kao
Keyword(s):  
Platelet Activation ◽  
Plasma Levels ◽  
Half Life ◽  
Degradation Products ◽  
Plasma Concentrations ◽  
Primary Source ◽  
Positive Correlation ◽  
Activation Marker ◽  
Fibrin Degradation Products ◽  
The Mean

SummaryThe use of plasma thrombospondin (TSP) concentration was investigated as an indicator of intravascular platelet activation. Patients (n = 20) with diseases that have known vasculitis were included in the study. The range and the mean of plasma TSP concentrations of patients with vasculitis were 117 ng/ml to 6500 ng/ml and 791±1412 ng/ml (mean ± SD); the range and the mean of plasma TSP concentrations of control individuals (n = 33) were 13 ng/ml to 137 ng/ml and 59±29 ng/ml. When plasma TSP concentrations were correlated with plasma concentrations of another platelet activation marker, β-thromboglobulin (P-TG), it was found that the TSP concentration inei eased exponentially as the plasma β-TG level rose. A positive correlation between plasma levels of plasma TSP and serum fibrin degradation products was also observed. The results suggest that platelets are the primary source of plasma TSP in patients with various vasculitis and that plasma TSP can be a better indicator than β-TG to assess intravascular platelet activation due to its longer circulation half life.

Covalent Complexes Between Low Molecular Weight Heparin Fragments and Antithrombin III – Inhibition Kinetics and Turnover Parameters

1983 ◽  
Vol 49 (02) ◽  
pp. 109-115 ◽  
Author(s):  
M Hoylaerts ◽  
E Holmer ◽  
M de Mol ◽  
D Collen
Keyword(s):  
Molecular Weight ◽  
Half Life ◽  
Low Molecular Weight Heparin ◽  
Antithrombin Iii ◽  
Factor Xa ◽  
Life Time ◽  
Low Molecular Weight ◽  
High Affinity ◽  
Plasma Half Life ◽  
Covalent Complex

SummaryTwo high affinity heparin fragments (A/r 4,300 and M, 3,200) were covalently coupled to antithrombin III (J. Biol. Chem. 1982; 257: 3401-3408) with an apparent 1:1 stoichiometry and a 30-35% yield.The purified covalent complexes inhibited factor Xa with second order rate constants very similar to those obtained for antithrombin III saturated with these heparin fragments and to that obtained for the covalent complex between antithrombin III and native high affinity heparin.The disappearance rates from plasma in rabbits of both low molecular weight heparin fragments and their complexes could adequately be represented by two-compartment mammillary models. The plasma half-life (t'/j) of both low Afr-heparin fragments was approximately 2.4 hr. Covalent coupling of the fragments to antithrombin III increased this half-life about 3.5 fold (t1/2 ≃ 7.7 hr), approaching that of free antithrombin III (t1/2 ≃ 11 ± 0.4 hr) and resulting in a 30fold longer life time of factor Xa inhibitory activity in plasma as compared to that of free intact heparin (t1/2 ≃ 0.25 ± 0.04 hr).

scholarly journals Biodistribution of the radiophamarceutical sodium pertechnetate (Na99mTcO4) after massive small bowel resection in rats

2007 ◽  
Vol 22 (6) ◽  
pp. 430-435 ◽  
Author(s):  
Dâmaso de Araújo Chacon ◽  
Irami Araújo-Filho ◽  
Arthur Villarim-Neto ◽  
Amália Cínthia Meneses Rêgo ◽  
Ítalo Medeiros Azevedo ◽  
...  
Keyword(s):  
Small Intestine ◽  
Short Bowel Syndrome ◽  
Intestinal Mucosa ◽  
Intestinal Resection ◽  
Small Bowel Resection ◽  
Control Group ◽  
Short Bowel ◽  
Massive Resection ◽  
Mucosal Thickness ◽  
Misleading Interpretation

PURPOSE: To evaluate the biodistribution of sodium pertecnetate (Na99mTcO4) in organs and tissues, the morphometry of remnant intestinal mucosa and ponderal evolution in rats subjected to massive resection of the small intestine. METHODS: Twenty-one Wistar rats were randomly divided into three groups of 7 animals each. The short bowel (SB) group was subjected to massive resection of the small intestine; the control group (C) rats were not operated on, and soft intestinal handling was performed in sham rats. The animals were weighed weekly. On the 30th postoperative day, 0.l mL of Na99mTcO4, with mean activity of 0.66 MBq was injected intravenously into the orbital plexus. After 30 minutes, the rats were killed with an overdose of anesthetic, and fragments of the liver, spleen, pancreas, stomach, duodenum, small intestine, thyroid, lung, heart, kidney, bladder, muscle, femur and brain were harvested. The biopsies were washed with 0.9% NaCl.,The radioactivity was counted using Gama Counter WizardTM 1470, PerkinElmer. The percentage of radioactivity per gram of tissue (%ATI/g) was calculated. Biopsies of the remaining jejunum were analysed by HE staining to obtain mucosal thickness. Analysis of variance (ANOVA) and the Tukey test for multiple comparisons were used, considering p<0.05 as significant. RESULTS: There were no significant differences in %ATI/g of the Na99mTcO4 in the organs of the groups studied (p>0.05). An increase in the weight of the SB rats was observed after the second postoperative week. The jejunal mucosal thickness of the SB rats was significantly greater than that of C and sham rats (p<0.05). CONCLUSION: In rats with experimentally-produced short bowel syndrome, an adaptive response by the intestinal mucosa reduced weight loss. The biodistribution of Na99mTcO4 was not affected by massive intestinal resection, suggesting that short bowel syndrome is not the cause of misleading interpretation, if an examination using this radiopharmaceutical is indicated.

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