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Biomedical subjects

A Paci

Publications and source records attributed to A Paci.

At least 19 recordsLinked to original sources
PubMed1996

Human placenta radioreceptor assay with digoxin and ouabain to detect endogenous digitalis-like factor(s) in human plasma and urine.

We describe the optimization and validation of a clinically feasible radioreceptor assay to detect endogenous digitalis-like factor(s) (EDLF) in human plasma and urine. The assay is based on the competitive replacement of 125I-labeled digoxin on human placenta membranes by ligands present in sample extracts. Digoxin and ouabain were used as calibrators. We also describe simple and effective methods for extraction and enrichment of EDLF from human plasma and urine. Assay sensitivity and precision were enhanced by using a sequential saturation technique with appropriate concentrations of tracer and receptors. Filtration was used to separate bound from free ligand. A two-step solid-state extraction with acetonitrile allowed the separation of two EDLFs with different polarity (EDLF-1 and EDLF-2) from the same plasma sample. A one-step solid-state extraction with methanol was suitable for urine. EDLF-1 and EDLF-2 in healthy adults were respectively 204 +/- 155 and 207 +/- 423 pmol/L ouabain equivalents, or 312 +/- 241 and 302 +/- 581 pmol/L digoxin equivalents. Plasma concentrations of EDLFs in newborns and pregnant women were higher than in healthy adults, and the concentrations in urine were higher than in plasma. Several cross-reactivity experiments showed that physiological concentrations of endogenous steroids and lipids did not inhibit binding, and supported the hypothesis that EDLFs are endogenous compounds other than the steroids and lipids also investigated.

Acetonitriles↗
PubMed1994

[Growth factors and oncogenes in development and carcinogenesis. Role of the epidermal growth factor system].

The processes of cellular proliferation and progressive acquisition of a specialized phenotype show a remarkable degree of coordination that involves both intracellular programming and intercellular communication. One of the major incentives for studying factors that regulate the processes of cellular proliferation and differentiation is the recognition of their potential contribution to tumorigenesis. In normal cells, stimulatory and inhibitory events are believed to be under the control of growth factors and growth inhibitory factors, which are known to be protooncogene products. Growth regulatory mechanisms usually involve the binding of a growth factor to a specific receptor on the cell surface, which then through an intracellular biochemical cascade leads to cell division. The cell regulation pathways initiated by growth factors may be subverted at several distinct levels in cancer cells. Studies of oncogenes have shown that they may function as abnormal growth factors or abnormal receptors, induce expression of potential signal regulators or encode proteins which modulate gene transcription. The purpose of the present paper is to examine the role of growth factors, growth factor receptors and intracellular proteins involved in signal transduction (with particular regard to the epidermal growth factor receptor system) in the control of normal growth and differentiation, and their contribution to transformation and tumorigenesis. We also review the classical theories of neoplasia and various other models. Chemical carcinogenesis and Vogelstein-Lane model are presented.

Amino Acid Sequence↗
PubMed1993

Endogenous digitalis-like activity in the newborn.

Elevated levels of endogenous digoxin-like immunoreactivity have been reported in the body fluids of premature and full-term infants as well as in term pregnancy, in the amniotic fluid, and in human milk. Several lines of evidence suggest that these factors could also have biological properties in common with digitalis: i.e., they could represent truly endogenous digitalis-like factor(s). In recent years we succeeded in partially purifying this factor from umbilical cord blood, which represents an easily available source of this factor. The inhibitory activity of this factor on 86Rb uptake could be neutralized by antidigoxin antibodies (Fab fragments) and provided, for the first time, direct evidence of an association between digoxin-like immunoreactivity and biological digitalis-like activity. In addition, these antibodies could be used for immunoaffine chromatography as a purification step before separation by high-performance liquid chromatography. Preliminary experiments suggest that this endogenous compound has both a tissue and an isoenzyme selectivity and is not a well-known steroid (testosterone, progesterone, 17-OH progesterone, cortisol, dehydroepiandrosterone sulfate, and estradiol).

Animals↗
PubMed1992

Endogenous digitalis-like factors in human milk.

We measured the concentration of endogenous digitalis-like factors (EDLFs) in milk or colostrum of women during nursing on different days after delivery. EDLF concentrations were assayed by a solid-phase RIA involving antidigoxin antibodies and by a radioreceptor assay (RRA) involving human placenta Na+/K(+)-ATPase. The mean (SD) EDLF concentrations as measured by RIA were 35.6 (19.4) ng of digoxin equivalents per liter in milk samples (n = 37) and 61.3 (12.5) ng/L in colostrum samples (n = 5); the mean EDLF concentration as measured by RRA in milk samples (n = 11) was 573 (717) ng/L (range 0-2098). EDLF concentration in milk is greater than circulating concentrations in healthy adults but is comparable with serum concentration in the third trimester of pregnancy. In milk and serum samples (n = 8) collected at the same time, heating and (or) extracting with Sep-Pak C18 cartridges before the RIA produced significantly different EDLF values from those in untreated serum (P less than 0.001) and milk (P = 0.035). EDLF in milk appeared to be not bound or weakly bound to milk protein, as indicated by the fact that boiling did not increase the digoxin-like immunoreactivity.

Blood Proteins↗
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↗
PubMed1990

[Ventricular arrhythmias in the acute phase of myocardial infarct and in the postinfarct. A 1-year follow-up].

A total of 90 AMI patients (80 male, 10 female; mean age: 62 years, range: 36-70 yrs) who were admitted to the coronary care unit within six hours of the onset of symptoms were evaluated for the following: the incidence and variability of complex ventricular ectopic beats (classes Lown III-V) in the acute, subacute and chronic phases of myocardial infarction. The diagnostic utility of Holter monitoring and treadmill exercise testing was compared so as to reveal complex ventricular ectopic beats. The relation between complex ventricular ectopic beats and left ventricular dysfunction was determined using the echocardiographic technique (ejection fraction, fractional shortening). The hospital mortality rate was 6.6% (6/9 patients) while the post-hospital mortality rate was 3.5% (3/84 patients). The prevalence rate of complex ventricular ectopic beats detected by Holter monitoring was respectively: 85.5% (77/90 patients) in the acute phase, 8.5% (7/80) at the 72nd hour, 18.5% (15/80) in the pre-discharge phase. At 1, 3, 6 and 12 months the prevalence rate was respectively 35% (27/77 patients), 28.8% (22/77), 24.6 (19/77), 24.6% (19/77). A high variability in arrhythmic groups was found. Each group was composed of new arrhythmic patients and stable arrhythmic patients, in addition to a small number of patients who were arrhythmic in the preceding control but no arrhythmic in the following control. This specific analysis of various groups revealed that the pre-discharge phase is the period with the highest number of "stable arrhythmic" patients (4 Holter positive out of 5) compared to the 1st month (3 Holter positive out of 4) and the 3rd month (2 Holter positive out of 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Binding of 14C-furosemide to isolated human erythrocytes.

The incubation of 14C-furosemide at high specific activity with intact red blood cells at 37 degrees C, pH 7.4, has enabled the furosemide binding sites to be characterized with respect to time course, affinity and specificity. The binding reaction was rapid, reversible and close to thermodynamic equilibrium. Binding was dependent on cell and furosemide concentration and was saturable. At equilibrium, pharmacological doses of furosemide competitively inhibited 14C-furosemide binding with 50% inhibition at 3 x 10(-5) M. The Na+/K+ pump inhibitor ouabain had no effect on the 14C-furosemide binding. Bumetanide, which is more potent than furosemide as inhibitor of Na+/K+ co-transport system and equally effective in inhibiting anion transport, was less effective than furosemide in displacing 14C-furosemide from its binding sites, suggesting a different mechanism of action for the two drugs in the red blood cell. The preincubation of erythrocytes with 4,4'-diisothiocyano-stilbene-2,2'-disulphonic acid (DIDS), the potent and specific inhibitor of anion permeability, reduced specific furosemide binding by more than 80% at a furosemide concentration of 0.1 microM, while it had little effect on the non-specific furosemide binding. Taken together, these data suggest that furosemide interacts with specific binding sites in the human red blood cell, whose nature has not been clarified, but whose location is probably on (or near) the protein in band 3, i.e. the membrane macromolecule-mediating anion transport.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1989

Lung tissue binding of iodobenzyl-propanediamine: involvement of beta-adrenergic receptors.

The basic compound N-N-N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3- propanediamine (HIPDM) accumulates in human and rabbit lungs, where it forms a slowly effluxable pool. In isolated perfused rat lung, HIPDM is taken up by a saturable, energy-independent mechanism, which is competitively inhibited by imipramine, chlorpromazine and propranolol. To ascertain whether beta-adrenergic receptors are involved in the binding process of HIPDM to lung tissue, the ability of unlabelled HIPDM to displace the beta-adrenergic receptor ligand [125I]iodocyanopindolol (ICYP) from rabbit lung beta-receptors was examined. Lung microsomal membrane fractions (75 micrograms ml-1) were incubated at 37 degrees C for 3 h with 68 pM ICYP (with or without 1 microM of (+/-)-propranolol) in the presence of HIPDM (10(-10)-10(-3) M). Bound and free radioactivity were separated through glass-fibre filters and the retained radioactivity was counted in a gamma-spectrometer. HIPDM competed with ICYP for beta-adrenoceptors (13% displacement at 10(-5) M. 50% at 5 x 10(-5) M, and 90% at 2 x 10(-4) M). The inhibition curve of ICYP binding by HIPDM was similar to that observed for (-)-noradrenaline. Although the results of the in vitro studies cannot be extrapolated to in vivo conditions, they suggest that beta-adrenergic receptors may be involved in the observed lung uptake of the basic amine HIPDM.

Animals↗
PubMed1989

Nimodipine in acute ischemic stroke: a double-blind controlled study.

Nimodipine (BAY e 9736), a new dihydropyridine derivative, has been shown to reduce neurological deficits and mortality induced by acute cerebral ischemia in experimental studies. We investigated the effects of this calcium antagonist in patients with acute ischemic stroke through a randomized, double-blind, parallel-designed trial in which nimodipine was compared with placebo. Forty-one of 54 screened cases were found to fulfil the inclusion criteria (sudden occurrence of a focal neurological deficit secondary to an acute ischemic event in the carotid area diagnosed after a complete neurological work-up) and entered the study. Nineteen of them were treated with nimodipine (40 mg t.i.d. administered for 28 days) and the remaining 22 with placebo, given in identical tablets. In all patients the treatment started within 12 h after the onset of the symptoms. Course and intensity of the neurological deficit were evaluated by the Mathew Scale (slightly modified). Forty patients concluded the trial. Nimodipine was withdrawn in one case following the occurrence of a skin rash whose causative relation with the test drug could not be clarified. Altogether, however, nimodipine was well tolerated and no severe cardiovascular adverse reactions were observed. In terms of efficacy, the scores obtained by the Mathew Scale showed a higher rate of improvement on nimodipine than on placebo, thus indicating that patients receiving the latter drug did not fare as well as those receiving the test medication. Our data suggest that nimodipine may be beneficial in the treatment of acute stroke.

Acute Disease↗
PubMed1989

[Katacalcin levels in healthy children and children with spasmophilia].

The calcitonin (CT) gene encodes at least 3 peptides: CT, the 21-aminoacid carboxyl-terminal flanking peptide (katalcin or PDN-21) and CT-gene related peptide. Normal thyroid C-cells as well as malignant ones co-secrete CT and PDN-21 in response to hypercalcemia, so assay of PDN-21 may be an usefull method to assess C-cells secretion. Because of our knowledge no data are available on PDN-21 values in children, we measured this peptide in healthy children and in spasmophilia (Sp), a disease that has been related to CT deficiency. We studied 16 healthy children (9 males, 7 females; aging from 3.0 to 11.6 years) and in 21 patients with diagnosed Sp (8 males, 13 females, aging from 4.6 to 13.0 years). PDN-21 were assayed in whole serum by RIA using synthetic human PDN-21 for standards, 125I-PDN-21 for tracer and specific antiserum. CT was measured the serum of the same subjects by RIA using an ultrasensitive methods. In healthy children PDN-21 serum values were 12.3 +/- 2.0 pg/ml and no significant differences were found between males and females. Children with Sp showed slow higher PDN-21 concentrations (14.0 +/- 1.4 pg/ml) than normals, but the difference was not statistically significant. Also CT values were not significantly different between normal children (21.4 +/- 3.7 pg/ml) and patients with spasmophilia (22.5 +/- 1.8 pg/ml). A high significant positive relation was found between katalcacin and CT levels in normals as well as in spasmophilics. The physiological effects of PDN-21 are actually unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Specific binding of cardiac glycoside drugs and endogenous digitalis-like substances to particulate membrane fractions from human placenta.

We studied the characteristics of binding of cardiac glycosides to particulate membrane fractions from human placenta, to demonstrate that placental tissue is a suitable source of receptors for digitalis drugs. Moreover, we performed preliminary experiments with 125I-labeled digoxin and placental particulates to develop a radioreceptor assay for measurement of endogenous substances with activity similar to cardiac glycoside drugs (EDLS). Placental membrane fractions were incubated with [3H]ouabain (10 nmol/L) or 125I-labeled digoxin (50 pmol/L). With both ligands, binding followed a pseudo-first-order reaction kinetics and was saturable. Scatchard analysis revealed a single class of sites [for ouabain, KD = 20.2 +/- 5.8 nmol/L (mean +/- SEM), Bmax = 3.1 +/- 0.9 nmol per gram of protein; for digoxin, KD = 29.7 +/- 1.9 nmol/L, Bmax = 24.3 +/- 1.1 nmol per gram of protein]. As expected, digoxin was less potent than ouabain in displacing both tracers from digitalis drugs receptors; progesterone, cortisone, digitoxose, furosemide, bumetanide, and propranolol had no or little effect. Specific 125I-labeled digoxin binding was competitively inhibited by plasma and (or) urine extracts from newborns, adults, pregnant women, and patients with renal insufficiency. Inhibition of binding and volume of plasma and urine assayed were linearly related. These findings support the hypothesis that cardiac glycosides and EDLS can interact with the human placenta and suggest placental tissue to be a suitable source of receptors for cardiac glycosides.

Binding Sites↗
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↗
PubMed1980

[Utility of angiography in the diagnosis and localization of hepatic carcinomas].

In the field of malignant primitive hepatic tumours, the use of ultrasonic methods and C.A.T. has made a considerable contribution to diagnosis and topographical localisation of such tumours. In addition, hepatic biopsy supplies the histological diagnosis. However it is only by angiography that it is possible to evaluate the involvement of the lobes and segments, supplying the character of invasiveness or otherwise of the lesion through demonstration of the arterial peduncle, and thus giving the surgeon the essential elements for a therapeutic approach. Furthermore, in the case of a monofocal lesion, it is only angiography that can establish the usefulness or otherwise of surgical therapy (William M. - Richard P. J. - Philip C. G. - Robert C. Lim, 1979). The purpose of the work is to examine the angiographic readings, which allow: 1) a diagnosis of hepatic expansive formation to be made, with definition of its nature (bening or malignant); 2) the growth character of the lesion to be characterised through evaluation of the involvement of the vascular structures.

Carcinoma↗