Surfactant metabolism of newborn lamb lungs studied in vivo

1980 ◽  
Vol 49 (6) ◽  
pp. 1091-1098 ◽  
Author(s):  
A. Jobe ◽  
M. Ikegami ◽  
I. Sarton-Miller ◽  
L. Barajas
Keyword(s):  
Palmitic Acid ◽  
Intravenous Injection ◽  
Half Life ◽  
Lamellar Body ◽  
Lung Parenchyma ◽  
Newborn Lamb ◽  
Specific Activities ◽  
Life Values ◽  
Surfactant Metabolism

Surfactant, microsomal, and lamellar body fractions were isolated from the lungs of 5-day-old lambs 0.21-55 h after the intravenous injection of radiolabeled palmitic acid. The specific activities as cpm/mumol phospholipid phosphate of phosphatidylcholine, saturated phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine were measured. The palmitate-labeled phospholipids disappeared from the lung parenchyma with a half-life of approximately 50 h. The radiolabel disappeared from phosphatidylcholine, saturated phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine of microsomal fractions with initial half-life values of 4.5, 4.6, 1.9, and 23.9 h, respectively. The labeled phospholipids rapidly appeared in the lamellar body fraction and accumulated in the surfactant of the lambs in a linear fashion for 35 h. The curves for the labeling of surfactant with radiolabeled saturated phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine were similar to the curve for phosphatidylcholine.

Turnover of Human Extrinsic (Tissue-Type) Plasminogen Activator in Rabbits

1981 ◽  
Vol 46 (03) ◽  
pp. 658-661 ◽  
Author(s):  
C Korninger ◽  
J M Stassen ◽  
D Collen
Keyword(s):  
Plasminogen Activator ◽  
Intravenous Injection ◽  
Active Site ◽  
Half Life ◽  
Degradation Products ◽  
Gel Filtration ◽  
Tissue Type ◽  
Organ Distribution ◽  
Small Rise

SummaryThe turnover of highly purified human extrinsic plasminogen activator (EPA) (one- and two-chain form) was studied in rabbits. Following intravenous injection, EPA-activity declined rapidly. The disappearance rate of EPA from the plasma could adequately be described by a single exponential term with a t ½ of approximately 2 min for both the one-chain and two-chain forms of EPA.The clearance and organ distribution of EPA was studied by using 125I-labeled preparations. Following intravenous injection of 125I-1abeled EPA the radioactivity disappeared rapidly from the plasma also with a t ½ of approximately 2 min down to a level of 15 to 20 percent, followed by a small rise of blood radioactivity. Gel filtration of serial samples revealed that the secondary increase of the radioactivity was due to the reappearance of radioactive breakdown products in the blood. Measurement of the organ distribution of 125I at different time intervals revealed that EPA was rapidly accumulated in the liver, followed by a release of degradation products in the blood.Experimental hepatectomy markedly prolonged the half-life of EPA in the blood. Blocking the active site histidine of EPA had no effect on the half-life of EPA in blood nor on the gel filtration patterns of 125I in serial plasma samples.It is concluded that human EPA is rapidly removed from the blood of rabbits by clearance and degradation in the liver. Recognition by the liver does not require a functional active site in the enzyme. Neutralization in plasma by protease inhibitors does not represent a significant pathway of EPA inactivation in vivo.

EFFECTS OF DIETARY IODINE ON THE UTILIZATION OF RADIOACTIVE IODIDE BY THE RAT

1963 ◽  
Vol 41 (7) ◽  
pp. 1547-1555 ◽  
Author(s):  
G. A. Robinson
Keyword(s):  
Thyroid Gland ◽  
Half Life ◽  
Sprague Dawley ◽  
High Iodine ◽  
In Vivo Measurements ◽  
Biological Half Life ◽  
Sprague Dawley Rats ◽  
Lower Protein ◽  
Life Values

Sprague–Dawley rats were fed on diets ranging from 40 μg I/kg to 3885 μg I/kg. Single doses of iodide-131 were injected intraperitoneally into each of the rats. In vivo measurements of radioisotope levels were made at intervals for 11 to 15 days over the neck and thorax. Thyroidal I131 curves were obtained by using a fraction of the thoracic counts to correct for the extrathyroidal component of the neck counts. Animals on low-iodine diets concentrated I131 in their thyroids more rapidly and to greater peak values, had lower protein-bound iodine (I127) concentrations, and lower total thyroidal iodide (I127) content than did rats in the high-iodine groups. An attempt was made to compensate the thyroidal counts for the continuing decrease in the concentration of iodide-131 in the plasma. From this attempt was derived the "thyroidal index", a parameter which may be related to the rate of exchange of the total thyroidal iodine stores. Biological half-life values (I131 in thyroid gland) for the low-iodine groups were larger than those for the high-iodine animals. The hypothesis is advanced that, at least for the conditions reported here, the biological half-life does not adequately reflect thyroidal activity; exchange of iodine between the rat and its environment is considered to be the more important factor in controlling the numerical value of this parameter.

Surfactant protein A metabolism in preterm ventilated lambs

1992 ◽  
Vol 262 (6) ◽  
pp. L765-L772 ◽  
Author(s):  
M. Ikegami ◽  
J. F. Lewis ◽  
B. Tabor ◽  
E. D. Rider ◽  
A. H. Jobe
Keyword(s):  
Gestational Age ◽  
Protein A ◽  
Lamellar Body ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Lamellar Bodies ◽  
Specific Activities ◽  
Kinetics Of

Surfactant protein A (SP-A) metabolism was studied in vivo in 33 preterm ventilated lambs at 138 +/- 1 days gestational age by measuring recoveries of exogenously administered surfactant containing both radiolabeled SP-A and labeled saturated phosphatidylcholine (Sat PC) given via the trachea at birth. Endogenously secreted SP-A was also labeled with [35S]methionine and followed over 24 h. The exogenously labeled SP-A left the alveolar pool more rapidly than did Sat PC over the first 5 h of life (P less than 0.05), and both exogenously labeled SP-A and Sat PC were detected within lamellar bodies by 2 h, indicating uptake from the airspaces. The quantity of SP-A in alveolar washes increased about twofold from birth to 5 h of age, whereas alveolar Sat PC pools were constant over 24 h. The SP-A endogenously labeled with [35S]methionine was recovered at highest specific activities in the alveolar washes at 10 and 45 min after birth with no labeled SP-A detectable in lamellar body fractions until 2 h. The curve for endogenous SP-A labeling of lamellar bodies was similar to that for exogenous labeling, indicating that SP-A was initially secreted by a pathway independent of lamellar bodies with subsequent SP-A labeling of lamellar bodies. The kinetics of SP-A metabolism were very different than for Sat PC in preterm lambs.

EFFECTS OF DIETARY IODINE ON THE UTILIZATION OF RADIOACTIVE IODIDE BY THE RAT

1963 ◽  
Vol 41 (1) ◽  
pp. 1547-1555 ◽  
Author(s):  
G. A. Robinson
Keyword(s):  
Thyroid Gland ◽  
Half Life ◽  
Sprague Dawley ◽  
High Iodine ◽  
In Vivo Measurements ◽  
Biological Half Life ◽  
Sprague Dawley Rats ◽  
Lower Protein ◽  
Life Values

Sprague–Dawley rats were fed on diets ranging from 40 μg I/kg to 3885 μg I/kg. Single doses of iodide-131 were injected intraperitoneally into each of the rats. In vivo measurements of radioisotope levels were made at intervals for 11 to 15 days over the neck and thorax. Thyroidal I131 curves were obtained by using a fraction of the thoracic counts to correct for the extrathyroidal component of the neck counts. Animals on low-iodine diets concentrated I131 in their thyroids more rapidly and to greater peak values, had lower protein-bound iodine (I127) concentrations, and lower total thyroidal iodide (I127) content than did rats in the high-iodine groups. An attempt was made to compensate the thyroidal counts for the continuing decrease in the concentration of iodide-131 in the plasma. From this attempt was derived the "thyroidal index", a parameter which may be related to the rate of exchange of the total thyroidal iodine stores. Biological half-life values (I131 in thyroid gland) for the low-iodine groups were larger than those for the high-iodine animals. The hypothesis is advanced that, at least for the conditions reported here, the biological half-life does not adequately reflect thyroidal activity; exchange of iodine between the rat and its environment is considered to be the more important factor in controlling the numerical value of this parameter.

Studies of the biosynthesis and metabolism of rat testicular galactoglycerolipids

1983 ◽  
Vol 61 (12) ◽  
pp. 1272-1281 ◽  
Author(s):  
Liu-Hsin Hsu ◽  
Rajagopalan Narasimhan ◽  
Mark Levine ◽  
Kenneth H. Norwich ◽  
Robert K. Murray
Keyword(s):  
Palmitic Acid ◽  
Early Stage ◽  
Turnover Time ◽  
Metabolic Stability ◽  
Cetyl Alcohol ◽  
Adult Rats ◽  
Slow Increase ◽  
Rat Testis ◽  
Specific Activities

1-O-Alkyl-2-O-acyl-3-O-β-D-(3′-sulfatoxygalactopyranosyl)-sn-glycerol (SGG) and its nonsulfated analog (GG) are the major glycolipids of rat testis. Aspects of the biosynthesis and metabolism of these two lipids have been investigated by determining their specific activities at various times after injection of [16-14C]palmitic acid, [1-14C]cetyl alcohol, and D-[1-14C]galactose into the testes of the adult rats. Evidence was obtained from studies with each of these three radioactive compounds that is consistent with the interpretation that GG exhibits a precursor relationship to SGG in vivo. The turnover time of GG, as estimated from the use of each of the three precursors, ranged between 21 and 69 h. In contrast, a slow increase of radioactivity in SGG was observed following injection of each of the three precursors, a plateau value being reached between 72 and 168 h. The radioactivity in the acyl, alkyl, and galactosyl moieties of SGG thereafter remained quite constant for another 21 days. Small amounts of monoalkylmonoacylglycerol were detected in rat testis. Radioactive studies indicated that this compound could be a precursor of GG and (or) monoalkyldiacylglycerol, another lipid that was also detected in rat testis. The results are consistent with the concept that the synthesis of SGG occurs primarily at an early stage of spermatogenesis and that the various moieties of this lipid exhibit almost complete metabolic stability during the subsequent complex stages of this process.

scholarly journals A Peptide-Based HIV-1 Fusion Inhibitor with Two Tail-Anchors and Palmitic Acid Exhibits Substantially Improved In Vitro and Ex Vivo Anti-HIV-1 Activity and Prolonged In Vivo Half-Life

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1134 ◽  
Author(s):  
Shan Su ◽  
Giselle Rasquinha ◽  
Lanying Du ◽  
Qian Wang ◽  
Wei Xu ◽  
...  
Keyword(s):  
Palmitic Acid ◽  
Half Life ◽  
Ex Vivo ◽  
Fusion Inhibitor ◽  
C Terminus ◽  
Further Development ◽  
Anti Hiv ◽  
Hiv 1

Enfuvirtide (T20) is the first U.S. FDA-approved HIV fusion inhibitor-based anti-HIV drug. Its clinical application is limited because of its low potency and short half-life. We previously reported that peptide HP23-E6-IDL, containing both N- and C-terminal anchor-tails, exhibited stronger potency and a better resistance profile than T20. Here we designed an analogous peptide, YIK, by introducing a mutation, T639I, and then a lipopeptide, YIK-C16, by adding palmitic acid (C16) at the C-terminus of YIK. We found that YIK-C16 was 4.4- and 3.6-fold more potent than HP23-E6-IDL and YIK against HIV-1IIIB infection and 13.3- and 10.5-fold more effective than HP23-E6-IDL and YIK against HIV-1Bal infection, respectively. Consistently, the ex vivo anti-HIV-1IIIB activity, as determined by the highest dilution-fold of the serum causing 50% inhibition of HIV-1 infection, of YIK-C16 in the sera of pretreated mice was remarkably higher than that of YIK or HP23-E6-IDL. The serum half-life (t1/2 = 5.9 h) of YIK-C16 was also significantly longer than that of YIK (t1/2 = 1.3 h) and HP23-E6-IDL (t1/2 = 1.0 h). These results suggest that the lipopeptide YIK-C16 shows promise for further development as a new anti-HIV drug with improved anti-HIV-1 activity and a prolonged half-life.

Clearance of surfactant protein B from rabbit lungs

1995 ◽  
Vol 268 (4) ◽  
pp. L636-L641 ◽  
Author(s):  
T. Ueda ◽  
M. Ikegami ◽  
M. Henry ◽  
A. H. Jobe
Keyword(s):  
Half Life ◽  
Lamellar Body ◽  
Surfactant Protein ◽  
Adult Rabbit ◽  
Lamellar Bodies ◽  
Surfactant Protein B ◽  
Clearance Kinetics ◽  
Protein B

To characterize the metabolism of surfactant protein B (SP-B) in vivo, we measured the clearance of SP-B from adult rabbit lungs. Purified rabbit SP-B was radiolabeled with 125I by the Bolton-Hunter method. Trace amounts of 125I-labeled SP-B mixed with [14C]dipalmitoylphosphatidylcholine (DPPC) were given intratracheally via a bronchoscope to rabbits 0-16 h before collection of alveolar washes (AW). Macrophages were recovered from AW, and lamellar bodies (LB) were isolated from lung tissue by differential centrifugation. 125I-SP-B was cleared more rapidly from the airspaces and the total lung (half-life 7 h) than was DPPC (half-life 11 h in the total lung). There was an approximately threefold accumulation of SP-B relative to saturated phosphatidylcholine in macrophages at all times. The proportion of 125I and 14C radioactivities in lamellar bodies was similar at 2 and 4 h, but there was 14-fold less 125I-SP-B than [14C]DPPC in lamellar bodies by 16 h. This loss of SP-B from the lamellar body fraction is consistent with less recycling of SP-B. The results demonstrate different clearance kinetics of these two components of surfactant and indicate a significant role of macrophages in the clearance of SP-B.

Physicochemical Properties, Bioconversion and Disposition of Lipophilic Prodrugs of 2′,3′-Dideoxycytidine

1996 ◽  
Vol 7 (3) ◽  
pp. 167-172 ◽  
Author(s):  
S.S. Ibrahim ◽  
F.D. Boudinot ◽  
R.F. Schinazi ◽  
C.K. Chu
Keyword(s):  
Mouse Brain ◽  
Half Life ◽  
Liver Homogenate ◽  
Brain Homogenate ◽  
In Vivo Studies ◽  
Mouse Serum ◽  
Lipophilic Prodrugs ◽  
Life Values

Lipophilic prodrugs of 2′,3′-dideoxycytidine (ddC), 4,5′-diacetyI-ddC (DAC), 4,5′-ditrimethylacetyl-ddC (DTMAC), 4,5′-dicyclopentylpropionyl-ddC (DCYPP) and 5′-cholesteryl-ddC (CHOL), were evaluated for their utility in improving brain delivery of the parent nucleoside. The lipophilicity of the prodrugs was greater, compared to ddC., with partition coefficient values increasing from 0.03 for ddC to 0.37,28, 63 and 483 for DAC., DTMAC., DCYPP and CHOL., respectively. Aqueous solubility was decreased proportionally to the increase in lipophilicity. Bioconversion studies were performed in phosphate buffer (pH 7.4), human serum, mouse serum, and mouse brain and liver homogenates. Whereas CHOL was stable in vitro in all media, DAC., DTMAC and DCYPP exhibited stability only in buffer, indicating that the hydrolytic reaction for these compounds was, predominately, enzymatically triggered. DCYPP was rapidly hydrolysed in mouse serum and liver and brain homogenates with degradation half-life values of 0.04, 0.35 and 0.34 h respectively. DAC had a longer half-life in mouse serum than did DTMAC (0.82 h vs. 0.38 h), however, in mouse brain homogenate DTMAC (t1/2=3.9 h) was more stable than DAC (t1/2= 1.6 h). Both of these pro-drugs were rapidly metabolized in the mouse liver homogenate with half-life values of 0.36 h for DAC and 0.23 h for DTMAC. In-vivo studies performed for ddC., DAC and DTMAC in mice showed that the relative brain exposure (re) of ddC was not improved by administering the prodrugs. DTMAC yielded a re value of 0.023 which was similar to that for ddC (re = 0.028), while no ddC was detected in brain after DAC administration. Thus, although all of the prodrugs were more lipophilic than ddC., delivery of ddC to the brain was not enhanced in vivo.

scholarly journals Comparative pharmacokinetics, distributions in tissue, and interactions with blood proteins of conventional and sterically stabilized liposomes containing 2',3'-dideoxyinosine.

1996 ◽  
Vol 40 (1) ◽  
pp. 225-229 ◽  
Author(s):  
P Harvie ◽  
A Désormeaux ◽  
M C Bergeron ◽  
M Tremblay ◽  
D Beauchamp ◽  
...  
Keyword(s):  
Protein Binding ◽  
Intravenous Injection ◽  
Half Life ◽  
Peak Level ◽  
Free Drug ◽  
Systemic Clearance ◽  
Blood Proteins ◽  
Sterically Stabilized Liposomes

The pharmacokinetics and distribution in tissue of 2',3'-dideoxyinosine (ddI) encapsulated in sterically stabilized liposomes have been evaluated in rats. Most of the sterically stabilized liposomes concentrated in the spleen with a peak level at 24 h after their intravenous injection. An extended half-life in plasma was observed for sterically stabilized liposomes (14.5 h) compared with that of conventional liposomes (3.9 h). The systemic clearance of ddI incorporated in sterically stabilized liposomes was 180 times lower than that of the free drug. The levels of in vitro and in vivo protein binding on both conventional and sterically stabilized liposomes were also evaluated. Results suggest that the amount of proteins associated with liposomes might not be the only factor involved in the in vivo clearance of liposomes, as this process may also be influenced by the nature of the bound blood proteins.

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