CONCENTRATIONS OF OESTRADIOL AND OESTRONE IN PLASMA, UTERUS AND OTHER TISSUES OF FETAL GUINEA-PIGS: THEIR RELATIONSHIP TO UPTAKE AND SPECIFIC BINDING OF [3H]OESTRADIOL

1981 ◽  
Vol 89 (1) ◽  
pp. 71-77 ◽  
Author(s):  
C. GELLY ◽  
C. SUMIDA ◽  
A. GULINO ◽  
J. R. PASQUALINI
Keyword(s):  
Guinea Pigs ◽  
Specific Binding ◽  
Biological Response ◽  
Maternal Plasma ◽  
The Other ◽  
Fetal Plasma ◽  
Fetal Tissues ◽  
Low Concentrations ◽  
Selective Retention

The concentrations of unconjugated oestradiol-17β and oestrone have been measured by radioimmunoassay in the plasma of fetal, newborn and immature guinea-pigs. In fetal plasma, the values of oestradiol ranged from 15 to 50 pg/ml with no significant variations with gestational age except for an abrupt increase at the very end of gestation (148 pg/ml). Low concentrations of oestradiol were also found postnatally (from not detectable to 31 pg/ml) as well as in maternal plasma (22 pg/ml). The values of oestrone were consistently higher in all plasma regardless of age (43–164 pg/ml). Oestrogen concentrations were also determined in the fetal uterus, lung, kidney and brain and were found to be as much as 60 times higher (per g tissue) than in plasma, especially in the fetal uterus which contained four to five times more than the other tissues. These data correlated well with a 20–90 times greater uptake of [3H]oestradiol by the fetal uterus compared with the other tissues after in-vivo administration of [3H]oestradiol to the fetuses. The selective retention of oestradiol was probably due to the presence of specific oestradiol binding in these fetal tissues, particularly in the uterus whose binding was 60–120 times higher than in the other fetal tissues. Thus, the levels of oestrogen in the circulation of fetal guinea-pigs are low, but the fetal uterus is capable of maintaining a higher concentration which may be important physiologically since oestradiol has been shown to evoke a biological response in the fetal guinea-pig uterus.

Glucose and lactate metabolism in vivo in ovine fetus

1980 ◽  
Vol 239 (3) ◽  
pp. E208-E214 ◽  
Author(s):  
R. L. Prior
Keyword(s):  
Specific Activity ◽  
Maternal Plasma ◽  
Fetal Weight ◽  
Plasma Lactate ◽  
Fetal Plasma ◽  
Lactate Turnover ◽  
Ovine Placenta ◽  
Brachial Vein ◽  
Ovine Fetus

The metabolism of glucose and lactate by the ovine fetus (123-128 days of gestation) was studied; a primed, continuous infusion of [2-3H]glucose and [U-14C]lactate into the brachial vein of six fetuses was used. Fetal plasma lactate concentrations averaged 2.12 +/- 0.25 mM and glucose concentrations averaged 9.3 +/- 1.3 mg/100 ml. Total plasma turnover of lactate was 5.22 +/- 0.7 nmol/h and that of glucose was 3.48 +/- 0.63 nmol x h-1 x kg fetal weight-1. Lactate was converted to glucose at a rate of 1.35 +/- 0.64 mmol x h-1 x kg fetal weight-1, which represented 21.6 +/- 6.0% of the lactate turnover. The percentage of glucose coming from lactate was 48.9 +/- 15.2. The specific activity of maternal plasma glucose was less than 4% of the specific activity of glucose observed in fetal plasma. No radioactivity could be detected in maternal plasma lactate. The data show that the ovine fetus or the fetal-placental unit can convert lactate to glucose by days 123-128 of gestation. A general model presented describes carbohydrate metabolism in the ovine placenta and fetus.

Enhancement by GTP of cAMP binding to hepatic nuclei and cytosol

1984 ◽  
Vol 246 (1) ◽  
pp. C131-C140 ◽  
Author(s):  
E. M. Rosenberg ◽  
A. D. Goodman ◽  
T. L. Lipinski
Keyword(s):  
Binding Proteins ◽  
Specific Binding ◽  
Photoaffinity Labeling ◽  
Deae Cellulose ◽  
Nuclear Extract ◽  
Liver Cytosol ◽  
Nuclear Binding ◽  
Low Concentrations ◽  
Relative Molecular Weight

In the present study we have demonstrated specific binding of 3H-labeled adenosine 3',5'-cyclic monophosphate (cAMP) to a nuclear extract from rat liver. GTP, GDP, and low concentrations of ATP and ADP increased nuclear binding of [3H]cAMP, and AMP inhibited [3H]cAMP binding. Photoaffinity labeling studies employing [32P]cAMP revealed four nuclear binding proteins [relative molecular weight (Mr) 36,000, 49,000, 54,000 and 57,000]. Unlabeled cAMP decreased [32P]cAMP binding to all four proteins, whereas GTP increased binding to the 57,000 protein. We also observed specific binding of [3H]cAMP in the liver cytosol, which was stimulated by GTP but not by ADP or ATP. Photoaffinity labeling studies of the cytosol in the absence of unlabeled nucleotides revealed three cAMP-binding proteins (Mr 36,000, 49,000, and 54,000). Unlabeled cAMP inhibited binding of [32P]cAMP to all three proteins, whereas in the presence of GTP there was binding of [32P]cAMP to a Mr 57,000 protein. Using DEAE-cellulose, we isolated from the nuclear extract and cytosol a cAMP-binding protein that responded to GTP with an increase in cAMP binding but was unaffected by GDP, ATP, ADP, and AMP. Guanosine imidodiphosphate did not affect cAMP binding, suggesting that the stimulatory effect of GTP may be mediated by phosphorylation. We speculate that alterations in intracellular GTP in vivo may modulate the binding of cAMP to a protein in the nucleus and cytosol.

scholarly journals Altered expression of IGFs and IGF-binding proteins during intrauterine growth restriction in guinea pigs

2005 ◽  
Vol 184 (1) ◽  
pp. 179-189 ◽  
Author(s):  
A M Carter ◽  
M J Kingston ◽  
K K Han ◽  
D M Mazzuca ◽  
K Nygard ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Guinea Pigs ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Altered Expression ◽  
Intrauterine Growth ◽  
Fetal Plasma ◽  
Fetal Tissues ◽  
Igf Binding ◽  
Igfbp 3

The IGF system is one of the most important endocrine and paracrine growth factor systems that regulate fetal and placental growth. We hypothesized that intrauterine growth restriction (IUGR) in guinea pigs is mediated by the altered expression of IGFs and/or IGF binding protein (BP) mRNAs in tissues and is related to growth of specific tissues. IUGR was induced by unilateral uterine artery ligation on day 30 of gestation, and fetal plasma, amniotic fluid and tissue samples were collected at 55–57 days (term about 68 days) from paired IUGR and control fetuses (n=6). Western ligand blotting and immunoblotting were used to compare IGFBP levels in plasma and amniotic fluid. Total RNA was extracted from placenta and fetal tissues, and the relative abundance of IGF-II and IGFBP-1–6 mRNA was determined by Northern blotting, using species-specific probes where available. IUGR fetuses had decreased (P<0.01, by Student’s t-test) placental weight and body weight with an increase in the brain:liver weight ratio. The principal IGFBPs in fetal plasma migrated at 40–35, 30 and 25 kDa and were identified as IGFBP-3, -2 and -4 respectively. IUGR was associated with elevated plasma IGFBP-2 and IGFBP-4 and reduced IGFBP-3 levels. IGFBPs were detected at low levels in amniotic fluid of control fetuses but at higher levels in IUGR fetuses. In IUGR placentae, there was a small increase in IGFBP-4 mRNA (P<0.05). IGFBP-2 mRNA increased (P<0.001) in liver of IUGR fetuses. IGF-II and IGFBP mRNA expression did not change in fetal muscle. The results are consistent with reduced IGF action, directly or through inhibition by IGFBPs, particularly by circulating and tissue IGFBP-2, as a potential causal factor in decreased growth of the placenta and certain fetal tissues.

An in vivo study of ovine placental transport of essential amino acids

2001 ◽  
Vol 280 (1) ◽  
pp. E31-E39 ◽  
Author(s):  
Cinzia L. Paolini ◽  
Giacomo Meschia ◽  
Paul V. Fennessey ◽  
Adrian W. Pike ◽  
Cecilia Teng ◽  
...  
Keyword(s):  
Amino Acids ◽  
Plasma Concentration ◽  
Essential Amino Acids ◽  
Maternal Plasma ◽  
Transport Systems ◽  
Fetal Plasma ◽  
Placental Transport ◽  
Rate Limiting ◽  
Pulse Flux

Under normal physiological conditions, essential amino acids (EA) are transported from mother to fetus at different rates. The mechanisms underlying these differences include the expression of several amino acid transport systems in the placenta and the regulation of EA concentrations in maternal and fetal plasma. To study the relation of EA transplacental flux to maternal plasma concentration, isotopes of EA were injected into the circulation of pregnant ewes. Measurements of concentration and molar enrichment in maternal and fetal plasma and of umbilical plasma flow were used to calculate the ratio of transplacental pulse flux to maternal concentration (clearance) for each EA. Five EA (Met, Phe, Leu, Ile, and Val) had relatively high and similar clearances and were followed, in order of decreasing clearance, by Trp, Thr, His, and Lys. The five high-clearance EA showed strong correlation ( r 2 = 0.98) between the pulse flux and maternal concentration. The study suggests that five of the nine EA have similar affinity for a rate-limiting placental transport system that mediates rapid flux from mother to fetus, and that differences in transport rates within this group of EA are determined primarily by differences in maternal plasma concentration.

scholarly journals Correlation between In Vitro Susceptibility of Scedosporium apiospermum to Voriconazole and In Vivo Outcome of Scedosporiosis in Guinea Pigs

2004 ◽  
Vol 48 (10) ◽  
pp. 4009-4011 ◽  
Author(s):  
Javier Capilla ◽  
Josep Guarro
Keyword(s):  
Brain Tissue ◽  
Guinea Pigs ◽  
Systemic Infection ◽  
The Other ◽  
Prolonged Survival ◽  
Scedosporium Apiospermum ◽  
In Vitro Susceptibility ◽  
Fungal Load

ABSTRACT We have evaluated the efficacy of voriconazole (VRC) in a systemic infection by Scedosporium apiospermum in immunodepressed guinea pigs. Animals were infected with two strains; one required a VRC MIC of 0.5 to 1 μg/ml, common for this fungus, and the other required a high MIC (8 μg/ml), unusual in this species. VRC prolonged survival and reduced fungal load in kidney and brain tissues of the animals infected with the first strain but was unable to prolong survival or to reduce fungal load in brain tissue for the latter strain.

High-density lipoproteins (HDL) stimulate placental lactogen secretion in pregnant ewes: further evidence for a role of HDL in placental lactogen secretion during pregnancy

1989 ◽  
Vol 120 (3) ◽  
pp. 423-427 ◽  
Author(s):  
A. Grandis ◽  
V. Jorgensen ◽  
L. Kodack ◽  
S. Quarfordt ◽  
S. Handwerger
Keyword(s):  
Physiological Role ◽  
Maternal Plasma ◽  
High Density ◽  
Placental Lactogen ◽  
High Density Lipoproteins ◽  
Indwelling Catheter ◽  
Fetal Plasma ◽  
Sds Page

ABSTRACT Previous studies from our laboratory showed that high-density lipoproteins (HDL) stimulate the release of human placental lactogen (PL) from cultured trophoblast cells from normal pregnant women. To determine whether HDL stimulates PL secretion in vivo, ovine HDL was infused over 2–5 min into 11 pregnant ewes (22 separate experiments) at 86–130 days of gestation via an indwelling catheter into the maternal jugular vein. The HDL, freshly prepared from the plasma of pregnant ewes by differential flotation ultracentrifugation, was greater than 99% purified as judged by SDS-PAGE. Plasma samples were obtained from the ewes before and at 0·5-h intervals for 6 h following the infusions and were assayed for PL by a specific homologous radioimmunoassay. The maternal infusion of HDL at doses of 302–784 mg (5·3–13·8 mg/kg body weight) stimulated significant increases in maternal plasma PL concentrations in six out of eight experiments (six ewes), and the infusion of 108–264 mg (1·9–4·6 mg/kg) stimulated plasma PL concentrations in two out of six experiments. In contrast, HDL at doses < 100 mg were without effect in eight experiments. The response to the HDL infusions was characterized by a sustained increase in plasma PL concentrations beginning 1·5–2·5 h after the infusions, reaching a maximum 274·2 ± 21·9% of the baseline value (P<0·001). In contrast, the maternal infusion of lipoprotein-free plasma proteins or saline had no effect on maternal plasma PL concentrations. Although the infusion of HDL into pregnant ewes stimulated an increase in maternal plasma PL concentrations, the infusion of HDL (0·8–22·0 mg/kg) into three fetuses in seven separate experiments had no effect on fetal plasma PL concentrations. The demonstration that HDL stimulates an increase in plasma PL concentrations in pregnant ewes strongly supports a novel physiological role for HDL in the regulation of PL secretion. Journal of Endocrinology (1989) 120, 423–427

scholarly journals Oral Hexadecyloxypropyl-Cidofovir Therapy in Pregnant Guinea Pigs Improves Outcome in the Congenital Model of Cytomegalovirus Infection

2010 ◽  
Vol 55 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Fernando J. Bravo ◽  
David I. Bernstein ◽  
James R. Beadle ◽  
Karl Y. Hostetler ◽  
Rhonda D. Cardin
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Day Treatment ◽  
Congenital Infection ◽  
Cmv Infection ◽  
Fetal Tissues ◽  
Pup Survival ◽  
Guinea Pig Model ◽  
Human Cmv

ABSTRACTCytomegalovirus (CMV) infection is the leading cause of congenital infection, producing both sensorineural hearing loss and mental retardation. We evaluated thein vivoefficacy of an orally bioavailable analog of cidofovir, hexadecyloxypropyl-cidofovir (HDP-CDV), against guinea pig CMV (GPCMV) in a guinea pig model of congenital CMV infection. HDP-CDV exhibited antiviral activity against GPCMV with a 50% effective concentration (EC50) of 0.004 μM ± 0.001 μM. To evaluatein vivoefficacy, pregnant Hartley guinea pigs were inoculated with GPCMV during the late second/early third trimester of gestation. Animals were administered 20 mg HDP-CDV/kg body weight orally at 24 h postinfection (hpi) and again at 7 days postinfection (dpi) or administered 4 mg/kg HDP-CDV orally each day for 5 days or 9 days. Virus levels in dam and pup tissues were evaluated following delivery, or levels from dam, placenta, and fetal tissues were evaluated following sacrifice of dams at 10 dpi. All HDP-CDV regimens significantly improved pup survival, from 50 to 60% in control animals to 93 to 100% in treated animals (P≤ 0.019). Treatment with 20 mg/kg HDP-CDV significantly reduced the viral load in pup spleen (P= 0.017) and liver (P= 0.029). Virus levels in the placenta were significantly reduced at 10 dpi following daily treatment with 4 mg/kg HDP-CDV for 5 or 9 days. The 9-day treatment also significantly reduced the viral levels in the dam spleen and liver. Although the 4-mg/kg treatment improved pup survival, virus levels in the fetal tissues were similar to those in control tissues. Taken together, HDP-CDV shows potential as a well-tolerated antiviral candidate for treatment of congenital human CMV (HCMV) infection.

scholarly journals Conversion of Cyanocobalamin to a Physiologically Occurring Form

Blood ◽  
1967 ◽  
Vol 29 (4) ◽  
pp. 494-500 ◽  
Author(s):  
PETER REIZENSTEIN ◽  
Nicolas Kulsdom
Keyword(s):  
Human Urine ◽  
Guinea Pigs ◽  
The Other ◽  
No Conversion ◽  
Approximate Rate

Abstract Results are presented which indicate that in guinea pigs cyanocobalamin undergoes conversion to hydroxocobalamin, in vivo and in vitro, at the approximate rate of 0.1-0.4 mµg./day/Gm. of liver. In boiled liver, no conversion was found. The radioactivity excreted in human urine the first 12 hours after a therapeutic cyanocobalamin dose, on the other, is still cyanocobalamin. It is suggested that demonstrated metabolic differences between therapeutically used cyanocobalamin and hydroxocobalamin are explained, in part, by the time needed to convert cyanocobalamin to hydroxocobalamin.

Comparison of maternal to fetal transfer of 3,5,3 ′-triiodothyronine versus thyroxine in rats, as assessed from 3,5,3′-triiodothyronine levels in fetal tissues

1989 ◽  
Vol 120 (1) ◽  
pp. 20-30 ◽  
Author(s):  
Gabriella Morreale de Escobar ◽  
María Jesís Obregón ◽  
Carmen Ruiz de Oña ◽  
Francisco Escobar del Rey
Keyword(s):  
Fetal Brain ◽  
Maternal Plasma ◽  
Constant Infusion ◽  
Rat Fetus ◽  
Fetal Plasma ◽  
Fetal Tissues ◽  
Thyroid Hormone Action ◽  
Fetal Thyroid ◽  
The Brain ◽  
Tsh Levels

Abstract. Thyroxine (T4) is transferred from the mother to the hypothyroid rat fetus late in gestation, mitigating T4 and T3 deficiency in fetal tissues, the brain included. We have now compared the effects of maternal infusion with T3. Normal and thyroidectomized rats were started on methimazole (MMI) on the 14th day of gestation, given alone, or together with a constant infusion of 0.45 μg (0.69 nmol) T3 or of 1.8 μg (2.3 nmol) T4/100 g per day. Maternal and fetal samples were obtained at the 21st day of gestation. The doses of T3 and T4 were biologically equivalent for the dams, as assessed from maternal plasma and tissue T3, and plasma TSH levels. MMI blocked the fetal thyroid; T4 and T3 levels were low in all fetal tissues, and fetal plasma TSH was high. Maternal infusion with T4 mitigated both T4 and T3 deficiency in all fetal tissues, the brain included, and decreased fetal plasma TSH. In contrast, infusion of T3 normalized fetal plasma T3 and increased the T3 levels in several tissues, but not in the brain. Neither did it decrease the high fetal plasma TSH levels. The results show that when the fetus is hypothyroid, T3 crosses the rat placenta at the end of gestation, but does not affect all tissues to the same degree. In contrast to the effects of maternal T4, maternal T3 does not alleviate the T3 deficiency of the brain or, presumably, of the thyrotrope. Thus, end-points of thyroid hormone action related to TSH release should not be used to measure transfer of maternal T3 to the fetal compartment. Moreover, T4 should be given, and not T3, to protect the hypothyroid fetal brain.

Free and bound androgens in the female guinea pig during gestation and after parturition and in the offsprings during the perinatal period

1980 ◽  
Vol 95 (1) ◽  
pp. 101-109 ◽  
Author(s):  
N. Rigaudière ◽  
P. Pradier ◽  
P. Delost
Keyword(s):  
Binding Capacity ◽  
Specific Binding ◽  
Equilibrium Dialysis ◽  
Plasma Concentrations ◽  
Perinatal Period ◽  
Maternal Plasma ◽  
Binding Activity ◽  
Low Concentrations ◽  
High Binding Affinity ◽  
Newborn Animals

Abstract. Total amounts of testosterone (T) and dihydrotestosterone (DHT) and their distribution between non-protein-bound (free), albumin-bound and PBG-(progesterone binding globulin)-bound fractions were determined by radioimmunoassay and equilibrium dialysis from plasma samples. The samples were taken from male guinea pigs during the perinatal period and from pregnant females during gestation and after parturition. Plasma proteins of the foetus and newborn animals appeared to have no high binding affinity for androgens. On the other hand albumin having a binding capacity of 56% for testosterone and 75% for DTH irrespective of the total androgen concentration may be considered to be an important low affinity binding protein. Maternal plasma developed a specific binding activity with the appearance of PBG in early pregnancy. Alterations in the binding capacity of PBG for T or DHT paralleled changes in plasma concentrations of both androgens, the highest values being observed on day 48 of pregnancy, with a prompt return to normal after parturition. Irrespective of the total androgen concentration, it was evident that PBG was capable of maintaining the free T and DHT at low concentrations (about 0.20 and 0.17 ng/10 ml, respectively). Besides the specific binding due to PBG a non-specific binding due to albumin was observed. The competition which exists between these two binding systems for T and DHT was evident when the quantity of bound androgens was expressed as a percentage. Neither the sex, nor the number of the foetuses, nor the interaction between the two, was found to have any significant effect in the maternal androgens, whether total or free hormone was considered.

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