PLACENTAL TRANSFER OF INSULIN-131I IN GUINEA PIGS IMMUNIZED AGAINST INSULIN

1966 ◽  
Vol 52 (2) ◽  
pp. 276-291 ◽  
Author(s):  
Jan I. Thorell

ABSTRACT The placenta is considered to be impermeable or only slightly permeable to insulin. Insulin antibodies are transferred from mother to foetus in man and in guinea pigs. The passage of insulin-131I from mother to foetus was studied in guinea pigs with and without antibodies against insulin. Antibody-bound insulin-131I was recovered in plasma from foetuses of immunized pregnant guinea pigs, at intervals of more than 5 hours after the injection of insulin-131I to the mother. The foetal levels of insulin-131I were rather low, the highest recorded value being 27% of the maternal plasma concentration. This peak was reached 32 hours after the injection. No insulin-131I was found in the foetuses of non-immunized guinea pigs.

PEDIATRICS ◽  
1971 ◽  
Vol 48 (4) ◽  
pp. 534-539
Author(s):  
Katherine C. King ◽  
Peter A. J. Adam ◽  
Robert Schwartz ◽  
Kari Teramo

At term, human growth hormone (HGH) does not cross the human placenta: therefore, the source of HGH in the fetal plasma is the fetal pituitary. In order to determine whether the fetal pituitary is also the only source of HGH secretion early in gestation, the maternofetal transfer of HGH-I125 was evaluated in four pregnant women receiving legal therapeutic abortions by abdominal hysterotomy. The plasma concentration of HGH-I125 was maintained until fetal delivery by a continuous infusion of the labeled hormone at 20 µc/hr for 170 to 225 minutes; and the plasma HGH-I125 concentration was determined by a specific immunoprecipitation. Even with maternal plasma levels of radioactive HGH between 875 and 1287 cpm/ml, no HGH-I125 was detected in either umbilical venous or arterial plasma, or in the amniotic fluid. As at term, no human placental transfer of HGH-I125 occurs early in gestation. Since the fetal hypophysis synthesizes, secretes, and stores HGH as early as 9 weeks in gestation, the fetal anterior pituitary apparently is the only source of HGH available to the human fetus.


1975 ◽  
Vol 64 (3) ◽  
pp. 511-520 ◽  
Author(s):  
B. T. DONOVAN ◽  
M. B. TER HAAR ◽  
A. N. LOCKHART ◽  
P. C. B. MACKINNON ◽  
J. M. MATTOCK ◽  
...  

SUMMARY The concentration of LH in the plasma of guinea-pigs from day 50 of gestation to day 45 of postnatal life was assayed by radioimmunoassay utilizing a cross-reaction with anti-ovine LH antiserum. The effect of gonadectomy in infancy and in the adult upon the plasma concentration of LH was also studied. The LH concentration in the plasma of male or female foetuses was high immediately prenatally and fell at birth. High levels of LH were again detected in male, with a lesser increase in female, guinea-pigs over the first 10 days postnatally. Maternal plasma concentrations of LH remained consistently low. Removal of the gonads on days 0, 5, 10, 15, 25 or 35 of postnatal life, followed by blood collection at autopsy 10 days later, caused a significant rise in plasma LH content at all ages. The rise in plasma LH after gonadectomy in adults was less marked in male than in female guinea-pigs.


1963 ◽  
Vol 205 (5) ◽  
pp. 845-847 ◽  
Author(s):  
Robert C. Meade

Insulin-binding antibodies were demonstrated in the serum of fetuses and newborn of insulin-treated guinea pigs. The antibody concentrations in fetal and maternal sera were comparable. Following delivery, the antibody decreased more rapidly in the newborn than in the mother. Antibodies injected into the maternal circulation were demonstrable in increasing concentration in the fetal circulation from 12 to 120 hr after maternal injection. These studies favor a mechanism of passive transplacental transfer of anti-insulin antibodies.


1981 ◽  
Vol 59 (4) ◽  
pp. 342-346 ◽  
Author(s):  
W. H. Harris ◽  
G. R. Van Petten

The placental transfer of indomethacin was studied in the rabbit at 30 days of gestation and in the sheep between 120 and 135 days of gestation. Plasma concentrations of indomethacin reached a maximum of 13.7 ± 1.6 and 10.9 ± 1.5 μg/mL in the doe and fetuses, respectively, at 1 h following a maternal subcutaneous injection of 10.0 mg/kg. The maternal plasma concentration of drug decreased rapidly but the fetal plasma concentration of drug remained elevated and exceeded that of the doe before decreasing. Indomethacin became detectable in the amniotic fluid after 2 h, reached a maximum of 3.2 ± 0.8 μg/mL at 4 h, and then gradually decreased. The intravenous infusion of 10.0 mg of indomethacin per kilogram over 30 min into a pregnant ewe resulted in a maximal plasma concentration of 13.5 ± 0.7 μg/mL in the ewe and 0.6 ± 0.1 μg/mL in the fetus at the termination of the infusion. The concentration of indomethacin in the amniotic fluid increased to a maximum of 3.5 ± 0.5 μg/mL 150 min after the infusion stopped. There was an increase in the percentage of drug bound by the fetal plasma proteins as gestation advanced. Thus there exists the possibility that the fetus would be exposed to increasing amounts of indomethacin as term approached.


1988 ◽  
Vol 116 (3) ◽  
pp. 381-385 ◽  
Author(s):  
T. M. Nguyen ◽  
A. Halhali ◽  
H. Guillozo ◽  
M. Garabedian ◽  
S. Balsan

ABSTRACT The effect of thyroparathyroidectomy (TPTX) on the plasma concentrations of the vitamin D metabolites (25-(OH)D, 24,25-(OH)2D and 1,25-(OH)2D) has been studied in pregnant rats and their fetuses during the last quarter of gestation. Maternal and fetal vitamin D metabolites were not significantly affected by TPTX. A significant increase in plasma 1,25-(OH)2D concentrations was observed in both TPTX and control mothers and fetuses from days 19 to 21. Fetal and maternal plasma 25-(OH)D were positively correlated in both control and TPTX groups. Such a correlation was also found for 24,25-(OH)2D in the two groups. In contrast, a positive correlation between maternal and fetal plasma concentrations of 1,25-(OH)2D was found in TPTX but not in control rats. These data suggest that major alterations in calcium metabolism, such as that produced by maternal TPTX, are insufficient to affect the changes in maternal and fetal plasma 1,25-(OH)2D during late pregnancy significantly. They also suggest that parathyroid hormone, thyroxine, and/or calcitonin may control a possible placental transfer of 1,25-(OH)2D in the rat. J. Endocr. (1988) 116, 381–385


1996 ◽  
Vol 30 (11) ◽  
pp. 1249-1251 ◽  
Author(s):  
Maria L Santeiro ◽  
Carine Stromquist ◽  
Lance Wyble

OBJECTIVE: To report phenoxybenzamine placental transfer in the treatment of maternal hypertension secondary to pheochromocytoma. CASE SUMMARY: A 22-year-old woman diagnosed with pheochromocytoma was medically managed at 33 weeks gestation with oral phenoxybenzamine and labetalol until delivery 26 days later. To determine phenoxybenzamine placental passage, at the time of cesarean section simultaneous samples were obtained from the cord blood, maternal blood, and amniotic fluid. Additional blood samples were obtained from the newborn at 32 and 80 hours of life. Mean concentrations of phenoxybenzamine from cord and maternal plasma and in amniotic fluid were 103.3,66, and 79.3 ng/mL, respectively; the newborn's plasma concentration at 32 hours of life was 22.3 ng/mL. At the time of delivery, the 2475-g male infant exhibited perinatal depression; mild transient hypotension was also noted for the first few days of life. DISCUSSION: The fetal—maternal plasma accumulation ratio of 1.6:1 indicates that at this gestational age after 26 days of therapy, the placental transfer of phenoxybenzamine occurs and is accompanied by accumulation in the fetal blood. CONCLUSIONS: Because of the placental transfer of phenoxybenzamine, mild perinatal depression and transient hypotension may occur in newborns of mothers receiving this medication. These newborns must be closely monitored during the first few days of life for respiratory depression and hypotension.


1969 ◽  
Vol 47 (11) ◽  
pp. 917-921 ◽  
Author(s):  
J. G. Manns ◽  
R. P. Brockman

Experiments were performed on 21-day-old rat fetuses to determine the effect of insulin or insulin antibodies on the incorporation of 14C-glucose into liver and muscle glycogen. Radioactive glucose was infused for 4 h into the maternal circulation; experiments were done on unanesthetized animals. Fetuses injected with insulin incorporated more 14C-glucose into liver glycogen than littermate controls; fetuses injected with insulin antibody incorporated less than their controls. The results suggest that insulin has a regulatory effect on the synthesis of fetal liver glycogen.


2007 ◽  
Vol 26 (3) ◽  
pp. 237-246 ◽  
Author(s):  
Lisbeth E. Gómez-Martínez

HEPP (D,L-3-hydroxy-3-ethyl-3-phenylpropionamide) is a novel anticonvulsant with promising anticonvulsant profile, which is being actively researched. The potential maternal and embryo/fetal toxicities of HEPP were evaluated in pregnant rats following subcutaneous (s.c.) administration during organogenesis (gestation days 6 through 14, GDs 6–14) and the fetal period (GDs 14–21). Single- and multiple-dose pharmacokinetics were also evaluated at the same periods in order to establish possible correlations with some maternal or embryo/fetal toxicity end points. Embryotoxicity was mainly indicated by a significant dose-concentration dependency in the increase in resorptions, high percentage of fully resorbed litters, and decrease in embryo body weights during the GD6–14 dosing period. No gross external alterations were observed in live fetuses. There was no indication of maternal toxicity; but a marked increase in maternal body weight was evident following dosing from GD14 to GD21. The maternal plasma profile following single subcutaneous dose of 50 mg/kg on both GD14 and GD21 showed a monoexponential elimination pattern. Statistically significant differences between treatments (GD14 versus GD21) were observed in elimination ( kel = 0.12 versus 0.15 h−1), absorption ( ka = 2.01 versus 3.14 h−1), maximum plasma concentration time points ( Tmax = 1.49 versus 1.01 h); maximum plasma concentration ( Cmax = 40.23 versus 36.31 μg/ml) and areas under the concentration-time curve (AUCs0– ∞ = 421.88 versus 274 μg h/ml. Based on comparisons of Cmax, Tmax, and AUCs0– ∞ between the actual data and single intraperitoneal (i.p.) data previously published, the s.c. administration exhibited slower disposition and higher absorbed amount. After multiple-dose administrations of 50 and 100 mg/kg every 12 h (07:00 and 19:00 h), steady-state plasma levels were lower than the computer prediction, and only slight accumulation was observed. In both dosing periods HEPP levels were similar in mothers and offspring at steady-state conditions. The high incidence of embryo death and reduced embryo weight at GD6–14 dosing compared to GD14–21 dosing suggest that embryos are more sensitive to the deleterious effects of HEPP than fetuses; however, the faster elimination observed at late gestation could also contribute to the lower toxicity observed during the fetal period. Because the maternal HEPP plasma levels and the AUC values were positively correlated with embryo/fetal toxicity end points, both pharmacokinetic parameters could be reliable indicators of offspring exposure and consequently of potential toxicity. These data suggest that the length of time that HEPP is present in the maternal plasma at a sufficiently high concentration could be determinant of adverse effects in the offspring.


1965 ◽  
Vol 122 (4) ◽  
pp. 771-784 ◽  
Author(s):  
Edward R. Arquilla ◽  
Jack Finn

1. Genetic factors control the configuration of combining sites of guinea pig insulin antibodies. 2. It is possible that the configuration of the combining sites of guinea pig insulin antibodies is controlled by more than one gene and not by multiple alleles at a given gene locus.


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