Search PubMed⌕ Search

Biomedical subjects

L Savu

Publications and source records attributed to L Savu.

At least 37 records · Page 2Linked to original sources
PubMed1987

alpha-Fetoprotein and transcortin behave as acute phase reactants in the maternal and fetal compartments of the inflammatory pregnant mouse.

Immunological and binding methods have been used to demonstrate that acute inflammation induced in the pregnant mouse by a single sc turpentine injection elicits plasma protein responses in the fetal as well as in the maternal compartment. The maternal response involves, along with the classical pattern of positive and negative acute phase reactants seen in the inflammatory nonpregnant animal, a highly specific approximately 2-fold increase of alpha-fetoprotein (AFP) concentrations. In addition, the high pregnancy-associated corticosteroid binding globulin (CBG) levels drop dramatically (2-3 times) in response to inflammation. The fetal response is characterized by small (10-25%) but statistically significant declines of AFP, CBG, and albumin concentrations, without any increase in levels of the positive classical acute phase reactants. The divergent responses of the estrophilic mouse AFP on the two sides of the placental barrier result in a 3- to 4-fold enrichment of the maternal serum vs. an approximately 20% impoverishment of the fetal serum in high affinity estrogen binding sites. The similar decrease in levels of CBG in mother and fetus leads to marked losses of high affinity corticosteroid sites for both. Neither the affinity constants for the estrogen-AFP interactions nor those for the corticosterone-CBG interactions are affected by inflammation. This is the first report of AFP as a positive marker of acute inflammation, of AFP as a pregnancy-specific inflammatory reactant in the mouse, and of a plasma protein response of the fetus in utero to an inflammatory stress undergone by the mother.

Animals↗
PubMed1987

[Demonstration and ontogenesis in the rat of a serum protein analogous to human thyroxine binding globulin].

It has been reported evidence based on equilibrium binding, electrophoretic, immunoelectrophoretic studies, that the rat possesses a major high affinity thyroid hormone binding protein, with an electrophoretic mobility and binding properties similar to those of the human thyroxine binding globulin (TBG). It is shown that in the sera of postnatal developing animals, between 3 and 21 days, the thyroxine (T4) and the triiodothyronine (T3) binding activities increase up to 10 times over adult or foetal levels, due to a high transient post-natal surge of the rat TBG. In the adult serum, the TBG persists in decreased amounts: it then yields the predominant role as T4 carrier to the thyroid binding prealbumin (TBPA), but retains the major role as binder of T3, i.e. of the biologically active thyroid hormone.

Aging↗
PubMed1986

High-affinity binding of testosterone in serum from normal developing chick embryos and during the graft-versus-host reaction.

The sera of developing chicken embryos contain high-affinity, low-capacity protein binding sites for testosterone. The affinities remain constant throughout development, with mean values for the association constants of approx. 3.6 X 10(8) M-1 at 25 degrees C, whereas the concentration of sites varies markedly as a function of age: from approx. 2 nmol/g serum proteins in 11-day embryos, it rises to a peak of approx. 5-8 nmol at 14-16 days, then drops to approx. 2.6 nmol at 18 days and only 0.8-1 nmol in adults. Testosterone binding is inhibited by corticosterone, progesterone and dihydrotestosterone, and is little affected by estradiol. The testosterone and corticosterone binding properties of chicken sera show close similarities: parallel ontogenic patterns; constant ratios, throughout development, of the equilibrium binding parameters of the two steroids; mutual binding inhibition. The evidence strongly suggests that the two activities are associated, at least in part, with a common protein carrier(s). In growing embryos which undergo a graft-versus-host reaction, elicited by the graft of adult spleen tissue at 9 days of age, the testosterone and corticosterone binding activities are significantly decreased. This decrease is due to a fall in the number of sites, whereas association constants are not affected. This is the first high-affinity, saturable, testosterone-binding property to be described in an embryonic serum.

Age Factors↗
PubMed1985

Total and unbound cortisol-, progesterone-, oestrone- and transcortin-binding activities in sera from patients with myocardial infarction: evidence for differential responses of good and bad prognostic cases.

Day-of-admission sera from myocardial infarction patients (MI) and patients with cardiopathies other than MI (non-MI) were analysed for total and unbound cortisol (F), progesterone (P4), oestrone (E1), and corticosteroid binding activities (CBG). The MI who survived (n = 28) showed high increases of F, P4 and E1 compared to healthy controls. By contrast, the MI who died within 10 days of admission (n = 6) had unchanged F and less increased P4 and E1 than survivors. The non-MI (n = 6) had higher F and E1 than controls but normal P4. The unbound steroids were increased in all patients: however, the MI who died showed much smaller rises than survivors (P less than 0.001 for unbound F and E1 increases in survivors vs. deceased). The CBG activity was in all MI lower than in normals (P less than 0.001) but unchanged in non-MI. These results are discussed in terms of the potential significance of unbound plasma steroids as predictors of MI severity.

Adult↗
PubMed1985

Serum inflammatory responses of transcortin binding activities and of total and free corticosterone and progesterone levels in developing rats: a kinetic approach.

The kinetics of the inflammatory responses of 5 serum parameters involved in specific protein-hormone interactions were studied, namely: transcortin (CBG) binding activities; total corticosterone (B), main ligand of CBG; unbound corticosterone (free B); total progesterone (P4), main competitor of B for binding on CBG; and the free P4. The studies were performed in developing animals, i.e. on rats given a single turpentine injection at 1, 10, 21 or 90 days of post-natal age. The responses showed similar trends at all ages, but age-dependent differences in kinetics and reactivities. Common characteristics were 3-5-fold increases of the hormone parameters as soon as 4-8 h after the injection, and 2-3-fold decreases in CBG activities. A remarkable age-dependent difference was the contrast of early CBG decrease in adults (4 h after turpentine) to the delayed occurrence of this reaction in immatures (8-24 h after turpentine). On the other hand, the increase of free B lasted for 72 h in neonates, but only 40 h in rats treated at 21 or 90 days. Age-dependent characteristics were seen also in reactivities: the peak increases in the hormone levels were highest in the young, while the peak decreases of CBG were most marked in the mature animals. The results suggest that the regulatory mechanisms governing the mutual effects of hormonal activities and CBG synthesis might depend on the stage of development.

Aging↗
PubMed1984

Age-dependent responses of the serum non-esterified fatty acids to adrenalectomy and ovariectomy in developing rats.

We report detailed gas chromatography analyses of the non-esterified fatty acids in the sera of female rats during post-natal maturation. A marked age-dependent decrease of concentration is demonstrated for all classes of compounds. Total levels fall from about 0.8 mM at birth to about 0.25 mM, 60 days later. The decrease is most pronounced for the polyunsaturated acids, which represent 27 +/- 9% of total fatty acids at birth and 13 +/- 3% 60 days later. The effects of ovariectomy and adrenalectomy on the free fatty acid levels as a function of age are strikingly different before and after maturation. When ovariectomy is performed at 5, 9 and 15 days, the fatty acid levels respond by a significant (30-40%) decrease; when adrenalectomy is carried out at the same ages, a dramatic 3-5-fold increase of all classes of fatty acids is observed. By contrast, in older animals, both responses have virtually disappeared. Possible mechanisms underlying the age-dependent patterns and behaviour of the serum free fatty acids are briefly discussed.

Adrenalectomy↗
PubMed1983

Turpentine-induced decrease of alpha 1-foetoprotein in the serum of the developing rat: a novel parameter of the inflammatory response.

The acute phase of an inflammation induced in young rats, at various ages between 1 and 21 days after birth, by a single subcutaneous turpentine injection, is accompanied by a 35%-45% decrease of the alpha 1-foetoprotein serum concentrations. This fall is demonstrated with equilibrium dialysis binding methods, evidencing the loss of about 1/3 of the high affinity estrogen binding sites characteristic for the rat foetoprotein, as well as by specific immunoassay of the foetoprotein concentrations. This negative response is coincidental with classical inflammatory changes of the plasma proteins, similar to those defined in adults: in particular we evidence 5 to 10 fold rises of haptoglobin, as early as the first post-natal day. We discuss the implications of these findings for ontogenic and mechanistic aspects of the inflammatory response.

Animals↗
PubMed1983

The role of nonesterified fatty acids and of alpha 1-fetoprotein in estrogen-dependent endocrine systems.

We discuss the various experimental findings to date that indicate that AFP may be considered as a positive or negative modulator of estrogenic action. Moreover, we show that this protein, even when nonestrogenophilic, is able to bind other hydrophobic ligands, in particular nonesterified fatty acids. These fatty acids inhibit the binding of estrogens to murine AFP as well as to the cytosolic estrogen receptors. Thus, the AFPs of all species--whether or not estrogenophilic--might play an endocrinologic role through the intermediary of the unsaturated fatty acids to which they associate with high affinity.

Animals↗
PubMed1982

Developmental patterns of levels of corticosterone and of corticosterone binding in the serum of female rats: effects of ovariectomy and adrenalectomy.

Corticosterone concentrations and corticosterone binding in the serum were studied in immature female rats, using radioimmunoassay and batchwise gel equilibrium techniques. A parallel developmental pattern was found for corticosterone levels and its serum binding with a neonatal drop, followed by low levels until 12 days of age and a rise between 12 and 28 days of age. Effects of adrenalectomy, of ovariectomy, of the combined operation and of sham-operations, performed at various ages, were also studied. Adrenalectomy performed at 5 days of age did not decrease serum corticosterone concentrations within a 6-day period whereas it did in older rats. Complete disappearance of corticosterone from the blood occurred only in adult rats after combined adrenalectomy/ovariectomy. Ovariectomy and sham-operations in the younger age groups (5-15 days) caused a gradual increase in corticosterone concentration with maximal values 6 days after operation or later. The response of corticosterone secretion to these operations became more moderate and quicker, i.e. more adult-like, at 28 days of age, the age where corticosterone concentrations in intact rats also seemed to reach a plateau at an adult-like level. Corticosterone binding changed only marginally after ovariectomy or sham-operations until 28 days of age, when an increase was induced by these operations. After adrenalectomy or combined adrenalectomy/ovariectomy, however, marked increases in serum binding of corticosterone were always seen. In summary: though a parallel developmental pattern of serum corticosterone levels and corticosterone binding was seen in the maturing rat, interference with the normal condition causes divergent responses in these two parameters. Moreover, the responses vary with maturational age.

Adrenalectomy↗
PubMed1981

Mouse alpha 1-fetoprotein and albumin. A comparison of their binding properties with estrogen and fatty acid ligands.

The binding of estradiol-17 beta (E2), diethylstilbestrol (DES), and polyene fatty acids, in particular arachidonate (C20:4), to alpha 1-fetoprotein (alpha-FP) and albumin purified from mouse embryo sera was studied using equilibrium dialysis and electrophoretic techniques. E2, arachidonate, and DES all bind to alpha-FP, but with decreasing strength. E2 is a high affinity, low capacity ligand (Ka approximately 0.8 X 10(8) M-1 and approximately 0.3 sites/mol of alpha-FP at 25 degrees C); arachidonate is a weaker ligand disposing of more sites (Ka approximately 0.3 X 10(7) M-1 and 4-5 sites/mol of alpha-FP); the binding of DES is of comparatively low affinity and capacity (Ka approximately 0.2 X 10(7) M-1 and n approximately 0.7/mol of alpha-FP). In spite of different structures and equilibrium parameters, E2, DES, and arachidonate are able to compete with each other for binding to the fetoprotein. The C22:4 and C22:6 fatty acids are also efficient concentration-dependent inhibitors of E2 or DES binding. Albumin binds the fatty acids and DES, but equilibrium parameters are different from those of alpha-FP. In particular, arachidonate is a better ligand for albumin, where it interacts with at least two classes of apparent sites (Ka1 approximately 0.3 X 10(8) M-1 and n1 approximately 1; Ka2 approximately 0.2 X 10(7) M-1 and n2 approximately 30). In contrast to alpha-FP, albumin virtually does not bind E2. Also, no competition could be demonstrated between DES and fatty acid ligands for binding to albumin. None of the studied interactions, with either albumin or alpha-FP, was modified even by high doses of bilirubin. The possible functions of the various binding activities present in fetal sera in the process of growth are discussed.

Animals↗
PubMed1980

The serum competitor of oestrogen--rat alpha 1-foetoprotein interactions. Identification as a mixture of non-esterified fatty acids.

The novel endogenous serum ligands of rat alpha 1-foetoprotein previously demonstrated in different mammalian sera were identified by g.l.c.--mass-spectrometric methods as a mixture of non-esterified long-chain and predominantly unsaturated fatty acids. Detailed comparative analyses of these ligands extracted from foetal- and pregnant-rat sera, rat amniotic fluid and foetal human sera are presented. We also show that an important fraction of these ligands remains associated with the rat alpha 1-foetoprotein after purification; analyses are given for the composition of this lipid moiety of the foetoprotein. The physiological relevance of these results is discussed.

Aging↗