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S Balzan

Publications and source records attributed to S Balzan.

At least 37 records · Page 2Linked to original sources
PubMed1991

Purification of endogenous digitalis-like factor(s) from cord blood of neonate by immunoaffinity chromatography.

We have previously shown that antidigoxin antibodies may neutralize partially purified endogenous digitalis like factor(s) present in newborn (umbilical cord) plasma. We here report on the preparation of an immunoaffinity chromatographic system (high affinity digoxin-binding antibodies (Fab fragments) bound covalently to Sepharose) for the purification of endogenous digitalis like factor(s). Neonate plasma extract loses all its biological digitalis-like activity (erythrocyte 86Rb uptake inhibition) after absorption on Sepharose coupled to Fab fragments but not after absorption on uncoupled Sepharose. Endogenous digitalis like factor(s) absorbed to Sepharose coupled to Fab fragments can be eluted by methanol. Subsequent HPLC separation indicate that at least two molecular species with digitalis-like properties are retained by antibodies bound to Sepharose and can be recovered with methanol.

Antibodies↗
PubMed1991

Partial purification of endogenous digitalis-like compound(s) in cord blood.

Increasing evidence indicates the presence of endogenous digitalis-like compound(s) in human body fluids. In this preliminary report, we describe a study of the partial purification by HPLC of these compounds in the plasma of neonates (who have particularly high concentrations of this substance) and adults. Plasma samples from neonates (cord blood) and adults, lyophilized and extracted with methanol, were applied on a 300 x 3.9 mm C18 Nova Pak column and eluted with a mobile phase of acetonitrile/methanol/water (17/17/66 or 14/14/72 by vol) and, after 30 min, with 100% methanol. We assayed eluted fractions for inhibitory activity of 86Rb uptake and for digoxin-like immunoreactivity. The elution profile revealed a first peak of inhibitory activity of 86Rb uptake at the beginning of the chromatography; another peak was eluted with the 100% methanol. The two peaks also cross-reacted with antidigoxin antibodies. Because the second peak could possibly reflect the nonspecific interference of various lipophilic compounds, we focused our attention on the first peak. For these fractions dose-response curves for 86Rb uptake and for displacement of digoxin were parallel, respectively, to those of ouabain and digoxin, suggesting similarities of digoxin-like immunoreactive substance to cardiac glycosides. Similar chromatographic profiles were also obtained for plasma from adults, suggesting that the endogenous glycoside-like compound(s) in the neonate may be the same as those in the adult.

Adult↗
PubMed1990

Endogenous digitalis-like factors: their possible pathophysiological implications with particular regard to the perinatal period.

Endogenous factors with biological and immunological activity similar to cardiac glycoside drugs (endogenous digitalis-like factors; EDLF) have been found in several tissues and body fluids of animals and humans. Detectable EDLF concentrations were found in blood and urine extracts of adults (normal healthy controls, hypertensive patients and salt-loaded healthy subjects), while higher levels were generally observed in plasma samples of pregnant women, newborns, and patients with renal insufficiency. The chemical characteristics of this endogenous factor are, at present, unknown, although it has been suggested that EDLF could be a substance with low molecular weight. Experimental studies and theoretical considerations suggest that EDLF, in addition to the ability to react with antibodies, might also bind to the specific cellular receptor of the cardiac glycosides and thus inhibit the membrane Na+/K(+)-ATPase (sodium pump). Therefore, it has been suggested that EDLF is an endogenous modulator of the membrane sodium-potassium pump, and that it could play a role in the regulation of fluids and electrolytes, in the myocardial muscular tone and also in the pathogenesis of hypertension.

Adult↗
PubMed1989

Comparison between endogenous digoxin-like immunoreactivity and 86Rb uptake by erythrocytes in extracts of human plasma.

1. To investigate endogenous cardiac glycoside-like compounds in plasma and their ability to inhibit the sodium pump, digoxin-like immunoreactivity [digoxin-like immunoreactive substance(s), DLIS] and 86Rb uptake by erythrocytes were measured in plasma extracts from normal adults, hypertensive adults and neonates. 2. DLIS levels in neonate plasma extracts were significantly higher than those found for normotensive or hypertensive adults. No difference was observed between normotensive and hypertensive subjects. DLIS was significantly increased when boiled plasma was extracted. 3. Extracts of boiled neonate and adult plasma inhibited 86Rb uptake. Instead, when boiling was omitted, no detectable inhibition was found in extracts of plasma from normotensive or hypertensive adult subjects. When present, the inhibition resulted from a depression of the ouabain-sensitive (sodium-pump-mediated) component, and, for the boiled neonate plasma only, also of the ouabain-resistant component. When the data from the different groups were pooled, a statistically significant inverse relationship between DLIS and erythrocyte 86Rb uptake was observed. Furthermore, in a subgroup of samples in which determinations were made before and after boiling in the same samples, an inverse correlation was found between changes in DLIS and changes in ouabain-sensitive (but not ouabain-resistant) 86Rb uptake. 4. Plasma extracts incubated with albumin at a physiological concentration significantly decreased (by approximately 20%) the inhibition of 86Rb uptake observed. 5. These findings support the existence of one or more endogenous compounds which both bind to antidigoxin antibodies and inhibit transmembrane cation transport. Part of this inhibition may, however, not involve the sodium pump. Furthermore, this chemically unidentified substance(s) may be bound to plasma proteins which partly reduce its action in vivo.

Adult↗
PubMed1988

Endogenous cardiac glycoside-like substances in newborns, adults, pregnant women and patients with hypertension or renal insufficiency.

In an attempt to confirm the presence of endogenous substances with cardiac glycoside-like activity, the biological and immunological cardiac glycoside-like activity was measured by a sensitive solid-phase radioimmunological assay (RIA), two radioreceptor assays (RRA), and a 86Rb uptake method in normal subjects and in some pathophysiological conditions characterized by sodium retention and volume expansion. Significant concentrations of digoxin-like immunoreactive substances (DLIS) were measured in plasma (or serum) of normal subjects while significantly higher levels were found in pregnant women, newborns and in patients with renal impairment, and in some with essential hypertension. Concentrations in urine of normal adults or newborns were several times higher than in plasma. The results obtained by RIA correlated with those obtained by RRA and 86Rb uptake methods. In 88 normal subjects, DLIS excretion rates (overnight urine collection) in men were significantly higher than in women (68.6 +/- 23.6 pg/min vs 50.9 +/- 21.0 pg/min, p less than 0.01). The DLIS excretion rates correlated with creatinine, Na and K urinary excretion rates, and also with the subjects' body weight, height, body mass index, and systolic blood pressure. These findings confirm the presence of endogenous substances with immunological and biological activity similar to cardiac glycosides in human body fluids and also confirm the hypothesis that these endogenous factors may be involved in fluid and electrolyte regulation in man. In addition, the present data indicate that urinary excretion of DLIS is dependent on body mass and renal glomerular filtration.

Adult↗
PubMed1987

Characterization of the carrier protein of digoxin-like immunoreactive substance in plasma.

The presence of an endogenous digoxin-like immunoreactive substance(s) (DLIS) has been reported in the plasma and urine of experimental animals and humans. This substance might have a role in arterial hypertension. Although the chemical structure of DLIS is at present unknown, several studies indicate that DLIS has a low molecular weight and is reversibly bound in serum to carrier proteins. We have investigated the carrier protein of DLIS in chromatographic studies, using neonate plasma eluted on a Sephadex G200 column. The chromatographic profile of digoxin-like immunoreactivity showed a major peak with a molecular weight of approximately 60,000 daltons and a smaller peak eluted after the salt region. When the major peak was chromatographed on a Sephadex G100 column only one single peak was obtained, which closely coincided with the elution peak of albumin. Chromatographic separation of neonate plasma on a Sephadex G25 revealed a major post-salt immunoreactive peak. When these fractions were incubated with purified human albumin and separated again on the Sephadex G25, a large immunoreactive peak corresponding to albumin was again found while the immunoreactivity after salt completely disappeared. Our data therefore strongly suggest that the endogenous digitalis-like factor is carried in plasma by albumin.

Blood Proteins↗
PubMed1986

Correlation between endogenous digoxin-like immunoreactivity and 3H-ouabain displacement on erythrocyte membranes in extracts of human plasma.

The existence of endogenous cardiac glycoside-like compounds and their property of being recognized by anti-digoxin antibodies is still a matter of controversy. In order to investigate this problem, endogenous digoxin-like immunoreactivity (measured by RIA) and digitalis-like radioreceptor activity (measured by displacement of 3H-ouabain from erythrocyte membranes) were assessed in plasma extracts of normal adults, pregnant women and newborns. These three groups were chosen because of their known widely different levels of digoxin-like immunoreactivity. Compared to adults, newborns and pregnant women had significantly higher levels not only of immunoreactivity but also of displacement of 3H-ouabain binding, the latter being due, according to Scatchard analysis, to a decrease of the affinity of ouabain to its cellular receptor rather than to its maximal binding capacity. Furthermore, immunoreactivity and binding displacement correlated significantly. Our data indicate that one (or more) compounds with cardiac glycoside-like properties (both immunological and at the receptor level) are present in the plasma of newborns and pregnant women, and confirm the idea that radioimmunological methods may be useful in studying endogenous inhibitors of the sodium pump.

Adult↗
PubMed1986

Acute hypotensive effect of calcium antagonists and endogenous digitalis-like immunoreactivity in human essential hypertension.

Evidence has been provided on the increased presence, in essential hypertension, of endogenous digitalis-like factor(s) [DLIS, digoxin-like immunoreactive substance(s)] able to cross-react with antidigoxin antibodies and to inhibit the membrane-bound sodium-potassium pump. An inhibition of the sodium pump could lead, in smooth muscle cells, to an increase of intracellular calcium ions and to an increase of total peripheral resistances. In this study the relation between plasma levels of DLIS and the acute hypotensive effect of a calcium antagonist (nifedipine) has been evaluated in a group of borderline to severe hypertensive patients and in a control group of normotensive subjects. The results obtained confirm that the hypotensive effect of nifedipine is related to pretreatment blood pressure and show, only in hypertensive patients, a significant relation of DLIS with both pretreatment blood pressure and blood pressure decrement induced by nifedipine. These findings are compatible with a possible role of DLIS in modulating cellular calcium handling.

Adult↗
PubMed1985

Chromatographic characterization of endogenous digoxin-like immunoreactive substances present in serum and urine of infants using gel filtration with Sephadex G 25.

We assayed digoxin-like immunoreactivity in the serum of 19 healthy neonates (blood sample from umbilical cord), not receiving digoxin therapy, using a solid-phase radioimmunological method. In addition, urinary concentrations of a digoxin-like immunoreactive substance (DLIS) were assayed throughout the first 10 weeks of extrauterine life in 50 healthy infants. The mean (+/- SD) serum DLIS concentration obtained was 211 +/- 60 ng/l digoxin equivalents (d.e.) while, in the urinary samples of the first day of life, the mean concentration was 818 +/- 560 ng/l d.e. (n = 20). These DLIS values in infants were higher (about 5- to 10-fold) than those previously observed in adults. In addition, urinary DLIS values were very high in the first week of life and fell quite rapidly in the next weeks of life. We used serum and urine pools from neonates for gel filtration experiments using a Sephadex G 25 column. In the urine sample we found some immunoreactive peaks eluted at the end and after the region of salts, while the chromatographic profiles of the serum pool showed only a major peak eluted with the peak of proteins. After boiling, the same serum pool showed an elution pattern characterized by a smaller immunoreactive peak eluted with that of proteins and by other peaks similar to those observed for the urine sample. Our study demonstrated that a substance or more substances which cross-react with digoxin-specific antibodies are present in blood and urine of healthy infants. In addition, our chromatographic studies indicate that DLIS is probably a low molecular weight substance(s) which circulate(s) in blood bound to a higher molecular weight molecule.

Chromatography, Gel↗
PubMed1984

Digoxin-like immunoreactivity in normal human plasma and urine, as detected by a solid-phase radioimmunoassay.

Reports on the presence of digoxin-like immunoreactive substance(s) (DLIS) in the plasma and urine of several animal species and a few human test subjects prompted us to undertake to confirm the presence of DLIS in plasma and urine of normal persons and to investigate some characteristics of this antibody-DLIS binding. For this purpose we used a modified radioimmunoassay kit involving antidigoxin antibody-coated test tubes and 125I-labeled digoxin to measure DLIS in urine and concentrated plasma of ostensibly healthy subjects. In 12 separate experiments with plasma the mean sensitivity was 5.12 (SD 1.11) pg per tube, expressed as digoxin. There was no significant cross reactivity with human serum albumin in concentrations up to 200 g/L. The mean DLIS value (in digoxin equivalents) for plasma from 24 normal subjects was 33.58 (SD 14.24) ng/L. Its mean concentration in urine from five subjects was 315.00 (SD 91.38) ng/L.

Adult↗
PubMed1981

[Chromosomal variability of 2 species of Nicotiana in fluid culture].

The chromosomal number in relation with the age of suspension culture of nicotiana glauca (NG) and the non tumorous N. glauca x N. langsdorffii hybrid has been studied. In both species, an higher variability of chromosome number is present in younger culture. Aged cultures show a stabilization, for NG, around the hexaploid number (3n = 72) and for NNT, which is an amphidiploid specie, on the tetraploid level (4n = 84). Both species show, with the age of culture, a decrease in plant regeneration capacity, which is not due to chromosomal variability, since young cultures are much more variable than older one.

Chromosomes↗
PubMed1981

Comparison of outward and inward Na+/K+ cotransport-mediated fluxes in erythrocytes of essential hypertensive patients. Preliminary results.

A hereditary defect in the outward ouabain-resistant, furosemide-sensitive (ORFS) Na+/K+ cotransport has recently been reported by Garay and Meyer in erythrocytes of essential hypertensive patients and some of their normotensive offsprings. Since Na+/K+ cotransport in erythrocytes operates bidirectionally, the same defect might be detectable in the ORFS component of K+ influx rate. To test this hypothesis outward and inward Na+/K+ cotransport measurements were performed in erythrocytes of hypertensives and normotensive controls. Our preliminary results confirm the observation of a reduced outward cotransport in essential hypertension and also suggest that inward cotransport may be reduced in essential hypertension.

Adult↗
PubMedDate not supplied

[Left hepatectomy].

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Controlled Clinical Trials as Topic↗
PubMedDate not supplied

Inhibition of rat Na+/K+-ATPase isoforms by endogenous digitalis extracts from neonatal human plasma.

An unique endogenous digitalis-like factor (EDLF) has been previously purified from human newborn cord plasma and its differential effects tested on the three well defined functional isoforms (alpha1, alpha2 and alpha3) of the alpha subunits of Na+/K+-ATPase in rat. EDLF specifically inhibits the enzymatic activity. It differs from ouabain by three criteria: a preincubation with the membranes is required for full activity, no effect on the rat cerebral alpha3 isoform and a steep dose-response curve with the same apparent potency for rat alpha2 and alpha1 isoforms of high (10(-7) M) and low affinity (3 x 10(-5) M) for ouabain. These results indicate that the Na+/K+-ATPase inhibitor involved in the regulation of sodium and body fluid volume and present in neonate and adult human plasmas is distinct from ouabain.

Animals↗