Digoxin-like Immunoreactive Substance Levels Research Articles

Role of Digoxin-Like Immunoreactive Substance in the Pathogenesis of Transient Tachypnea of Newborn

Background. Transient tachypnea of newborn (TTN) is usually observed in term or near-term infants. It constitutes an important part of the respiratory distress cases observed in the neonatal intensive care unit (NICU). Aim. This paper examines the effects of digoxin-like immunoreactive substance (DLIS) on fluid and ion balance, hemodynamic and echocardiographic parameters of neonates with TTN. Methods. Plasma DLIS, Na+, K+, urea, creatinine, serum and urine osmolarity, urine FeNa+, 24-hour urine output, echocardiographic investigation and mean blood pressure, and clinical parameters of disease severity were recorded in TTN group and compared with control on the 1st and 7th days of their lives. Results. Plasma DLIS levels were statistically higher in TTN group (0.66 ± 0.37 ng/mL) compared to control group (0.24 ± 0.20 ng/mL) both on the 1st day (P < 0.01) and the 7th day (P < 0.05). For TTN group, significant correlation was found between plasma DLIS levels and maximum respiratory rate, duration of tachypnea, and length of hospitalization on the 1st day. Plasma DLIS levels were correlated negatively with serum osmolarity levels. Plasma DLIS levels were positively correlated with urine output, urinary FeNa+ levels, cardiac output, left ventricles end diastolic diameters, and right ventricles end diastolic diameters. Conclusions. Increased DLIS levels were correlated with disease severity in cases with TTN. This increase may be a primary or secondary event in the disease progress. It may help reduce the fluid overload due to already disturbed cardiac functions in patients by increasing urine output and natriuresis; however it may also contribute to disease pathogenesis, by inhibiting alveolar Na+-K+-ATPase which further decreases fetal alveolar fluid resorption.

Plasma and cerebrospinal fluid endogenous digoxin-like immunoreactivity in patients with aneurysmal subarachnoid haemorrhage.

Recent evidence indicates the presence of naturally occurring digitalis-like compounds in mammals, collectively known as either digitalis-like (DLF) or ouabain-like (OLF) factors, presumed to be endogenous hormones regulating the biological activity of the NA+/ K(+)-ATPase and its isoforms. This substance has been postulated to enhance renal tubular sodium excretion and to increase peripheral vascular resistance. Digoxin-like immunoreactive substance (DLIS) was observed in plasma of some patients with spontaneous subarachnoid haemorrhage (SSAH). Accumulating evidence suggests the central nervous system as a site of synthesis, but also as a site of hypertensinogenic action of endogenous cardioglycosides. The present study intends to establish the ratio of the DLIS in plasma to that in cerebrospinal fluid (CSF) in patients with SSAH and to investigate possible connection of this substance with development of arterial vasospasm. A prospective analysis of DLIS levels was performed on plasma and CSF samples obtained in 40 patients who had suffered a recent SSAH. DLIS levels were determined by the fluorescence polarisation immuno-assay method immediately after the admission to the Ward, and again seven days later. The comparison of CSF and plasma DLIS levels did not show statistically significant differences between the results--neither for the first (Z = 0.530; P = 0.591) nor for the seventh day after the disease onset (Z = 0.448; P = 0.654). Three possible hypothetical explanations of these results are offered: a) substance determined by digoxin immuno-assay has no essential likeness to digoxin; b) loss of the haemato-encephalic barrier integrity enabling free substance exchange between plasma and central nervous system; c) digoxin-like substance production within the central nervous system. Further, comparison of DLIS plasma levels (7th day from onset of SSAH) with angiography results showed that patients with multiple vasospasm had essentially higher plasma DLIS levels compared to patients with no vasospasms (Z = 2.59; P = 0.0097). The amount of extravasated blood, assessed on the basis of cranial CT scanning, was also connected with higher plasma DLIS levels (X2 = 3.29; P = 0.0305). The enhanced arterial narrowing which occurs in SSAH may be in part mediated by increased digitalis-like factor activity.

Digoxin-like immunoreactive substance and sodium-potassium-adenosine triphosphatase inhibition in normal pregnancy: A longitudinal study

To measure the levels of digoxin-like immunoreactive substance and digitalis-like factor bioactivity as manifested by sodium-potassium-adenosine triphosphatase (ATPase) inhibition throughout pregnancy. Serum samples were collected from primigravidas in early (15 +/- 1.8 weeks), mid (26 +/- 1.2 weeks), and late (36 +/- 1.1 weeks) gestation, as well as at 6 +/- 1.1 weeks postpartum (mean +/- standard error). Digoxin-like immunoreactive substance levels were determined by radioimmunoassay and digitalis-like factor bioactivity was determined by inhibition of ATPase. Data were analyzed by means of repeated measures analysis of variance. In 41 women with normal pregnancy outcomes, levels of digoxin-like immunoreactive substance rose progressively and significantly (P < .001) throughout pregnancy and returned to normal levels postpartum. Inhibition of ATPase activity also rose significantly (P < .004), but not as dramatically, during pregnancy and remained elevated 6 weeks postpartum. Although digoxin-like immunoreactive substance levels rise in pregnancy, functional digitalis-like factor activity, as manifested by inhibition of ATPase, does not parallel this rise strictly, implying that digoxin-like immunoreactive substance receptors may be reset during normal pregnancy. The enhanced cardiac performance that occurs in normal pregnancy may be mediated in part by increased digitalis-like factor activity.

The influence of feeding regimens on endogenous digoxin‐like immunoreactive substance concentrations in infants

The aim of this study was to investigate serum digoxin-like immunoreactive substance (DLIS) levels in 60 healthy term infants when they reached 1-6 months of age with regard to feeding regimen. Group I consisted of 30 infants fed exclusively on breast milk. Groups II and III each consisted of 15 infants fed on formula and cow's milk, and on formula and cow's milk supplemented by breast milk, respectively. Mean serum DLIS concentrations were 0.03 +/- 0.05, 0.18 +/- 0.09 and 0.15 +/- 0.09 ng/ml in groups I-III, respectively. The difference between the DLIS levels in groups II and III was not significant. Serum DLIS levels of infants in groups II and III, on the other hand, were significantly higher than in group I (p < 0.05). These findings were interpreted to suggest that artificial nutrients may cause volume expansion and an increase in endogenous DLIS levels. The latter response is possibly a protective mechanism to decrease volume expansion in groups II and III.

The influence of tocolytic therapy on serum digoxin-like immunoreactive substance concentration.

Digoxin-like immunoreactive substance (DLIS) has been proposed to have a role in what seems to be the timely onset of labor. The relationship between the DLIS in patients with preterm labor and the success of tocolytic therapy with ritodrine and nifedipine has been studied. Using a commercially available radioimmunoassay kit, DLIS levels were determined in a total of 47 women with preterm labor and in 30 control. Tocolysis was successful in 37 of 47 women, in 20 of whom nifedipine and in 17 ritodrine was the tocolytic agent. Mean DLIS concentration was higher in patients with preterm labor. Moreover, DLIS levels were found to be decreased by successful tocolysis as could be observed from the values before initiation of tocolytic therapy and on the 3rd day of tocolysis for both nifedipine (0.268 +/- 0.198 vs. 0.220 +/- 0.210 ng/ml) and ritodrine (0.250 +/- 0.176 vs. 0.196 +/- 0.147 ng/ml; Wilcoxon test, p < 0.05).

DIGOXIN-LIKE IMMUNOREACTIVE SUBSTANCE IN URINE FROM CHILDREN WITH IDIOPATHIC NEPHROTIC SYNDROME

Levels of digoxin-like immunoreactive substance (DLIS) were measured in the urine from patients with idiopathic nephrotic syndrome (INS), secondary nephrotic syndrome (SNS) or poststreptococcal acute glomerulonephritis (PSAGN) by radioimmunoassay. DLIS was detected only in the urine from INS patients, not in that from patients with SNS or PSAGN. There was no correlation between the level of DLIS in urine and the increase in body fluid. An oral dose of prednisolone did not influence the level of DLIS. In each INS patient, the DLIS/creatinine ratio in urine was raised to the maximum level at the diuretic stage. In order to clarify the characteristics of DLIS in INS patients, DLIS was extracted from patients' urine using both gel-chromatography and affinity-chromatography. Then DLIS was purified with reversed-phase high-performance liquid chromatography. Its molecular weight and polarity were very similar to those of digoxin. The intravenous injection of an extract containing DLIS induced significant increases in both urine volume and urinary sodium excretion in rats. Moreover, the purified DLIS inhibited Nat, Kt-ATPase in vitro. These results suggest that DLIS in urine from INS patients is associated with the clinical state and has natriuretic activity.

Digoxin-like immunoreactive substance in urine of patients with mucocutaneous lymph node syndrome (MCLS).

Levels of digoxin-like immunoreactive substance (DLIS) and dehydroepiandrosterone sulfate (DHEA) in urine from patients with mucocutaneous lymph node syndrome (MCLS) were measured by radioimmunoassay. Because DLIS of stored samples was often below the level of detection by conventional immunoassay, the authors used 80% ammonium sulfate and extraction with phosphate buffer and then 80% hot ethanol. To study the origin of raised levels of DLIS in urine, the synthesis of DLIS by cultured human umbilical vein endothelial cells (HUVEC) was tested in vitro. The correlation between DLIS and DHEA levels was not significant. Mean levels of urinary DLIS corrected for creatinine in the patients with MCLS were significantly higher than in both normal and diseased controls. The culture medium of HUVEC was found to contain DLIS activity. These results show that MCLS should be added to the clinical states associated with an increased urinary concentration of DLIS and that the endothelial cells are one source of DLIS in man.

Digoxin-like immunoreactive substance levels in cord blood obtained from twins

Digoxin-like immunoreactive substance levels in cord blood obtained from twins

A longitudinal study of maternal digoxin-like immunoreactive substances in normotensive pregnancy and pregnancy-induced hypertension

The serum of women in the third trimester of pregnancy demonstrates cross-reactivity with some commercially available antibodies to digoxin. A number of studies have suggested that levels of this digoxin-like immunoreactive substance(s) are further increased in patients with pregnancy-induced hypertension, and some have proposed that the digoxin-like immunoreactive substance could be useful as a predicitor of pregnancy-induced hypertension. We measured digoxin-like immunoreactive substance levels every 2 weeks throughout the third trimester in 170 women; of these, 20 developed hypertension. Digoxin-like immunoreactive substance levels rose with gestational age. A graph of the slope of digoxin-like immunoreactive substance plotted against gestational age was fitted for the results obtained from each woman. There was no significant difference in the mean rate of increase of digoxin-like immunoreactive substance level per week between pregnancy-induced hypertension and normotensive pregnancy, nor was there any difference between these two groups at any gestational age studied. These results suggest that measuring digoxin-like immunoreactive substance levels is not useful as a predictor of pregnancy-induced hypertension.

Atrial natriuretic factor, digoxin-like immunoreactive substance, norepinephrine, epinephrine, and plasma renin activity in human fetuses and their alteration by fetal disease

We measured five hormones presumably involved in fetal homeostasis in specimens obtained by cordocentesis for clinical indications from 106 fetuses. Norms for atrial natriuretic factor, digoxin-like immunoreactive substance, plasma renin activity, norepinephrine, and epinephrine were derived from fetuses ultimately shown to be free of detectable abnormality. Atrial natriuretic factor, digoxin-like immunoreactive substance, and plasma renin activity were unrelated to umbilical vessel source or gestational age. Digoxin-like immunoreactive substance was directly related to Pco2 (r = 0.63, p = 0.02). Digoxin-like immunoreactive substance level was elevated in all fetal disease states studied except isoimmunization. The level of atrial natriuretic factor was elevated in fetuses with immune hydrops (NS). Norepinephrine and epinephrine levels were higher in the umbilical artery than in the vein (p = 0.05 and 0.006, respectively). There was a significant correlation between norepinephrine and gestational age in normal fetuses (r = 0.7637, p < 0.025) and between both catecholamines and many of the respiratory blood gas measurements, with pH and Pco2 being the major determinants. Most disease states were associated with an elevated norepinephrine concentration. There was a negative correlation between plasma renin activity and base deficit (p < 0.0001). Plasma renin activity was elevated in fetuses with idiopathic growth retardation and nonimmune hydrops (p < 0.05 for each). In summary, fetal homeostasis as reflected by these five hormones was altered by a variety of disorders. With these baseline values the effects of direct or indirect fetal therapy can begin to be studied.

Digoxin-like immunoreactive substance in pregnancy

Our aims were to determine the potential usefulness of digoxin-like immunoreactive substances in the prediction of preeclampsia, to study the relationship between fetal production of these substances and maternal serum levels, and to evaluate the association between digoxin-like immunoreactive substances and plasma volume findings in preeclamptic pregnancies. Serum digoxin-like immunoreactive substance concentrations were measured in normotensive and preeclamptic pregnant women and in umbilical artery and vein blood samples. None of the patients in the first trimester (n = 53) and 11% of those in the second (n = 56) had detectable levels of this substance. However, 91% of the patients in the third trimester (n = 161) had positive results. The concentrations of digoxin-like immunoreactive substances in the preeclamptic group (n = 78) were significantly (p less than 0.005) lower than those of third-trimester (n = 83) normotensive patients (0.22 +/- 0.12 versus 0.32 +/- 0.15 ng/ml). However, there were no significant differences between the two groups regarding digoxin-like immunoreactive substance concentrations when matched for gestational age (41 patients in each group). Digoxin-like immunoreactive substance concentrations in umbilical vessels were significantly higher (p less than 0.001) than the corresponding maternal levels. Umbilical vessel digoxin-like immunoreactive substance levels demonstrated good correlation with fetal gestational age and birth weight in both normotensive and preeclamptic pregnancies. On the other hand, there was a poor (r = 0.02; p = 0.91) correlation between plasma volume findings and digoxin-like immunoreactive substance concentration. We conclude that the digoxin-like immunoreactive substance level may be of very little value in the prediction of preeclampsia. The presence of digoxin-like immunoreactive substance at greater concentrations in the umbilical cord blood samples suggests the possibility of the fetus as the source of this substance. Digoxin-like immunoreactive substances may not play a major role in plasma volume expansion during pregnancy.

Urinary digoxin-like immunoreactive substance in pregnancy: Relation to urinary electrolytes

High concentrations of digoxin-like immunoreactive substance (DLIS) have been identified in amniotic fluid and in blood during pregnancy. In this study, urine from healthy women was analyzed for DLIS during pregnancy and following delivery, and levels were related to various clinical and urinary findings. Urinary DLIS increased progressively during pregnancy, having a linear relation to gestational week (DLIS = 0.032 week + 0.46, Syx = 0.52, r = 0.46, p <0.01), and fell to nonpregnant values during the first postpartum day. The urinary DLIS level correlated with urinary creatinine (r = 0.50, p <0.01) and urinary calcium (r = 0.56, p <0.01) levels. When adjusted for the gestational week, the urinary DLIS level also correlated with urinary potassium (r = 0.48, p <0.01), creatinine (r = 0.55, p <0.01), and magnesium (r = 0.55, p <0.01) levels. After adjustment for the urinary creatinine level, only the relation of urinary DLIS and urinary calcium levels remained significant (r = 0.44, p <0.05). The urinary DLIS level was not found to be related to systemic blood pressure. The ratios of sodium to potassium (r = −0.43, p <0.05) and calcium to magnesium (r = 0.37, p <0.05) were also related to gestational week but were independent of the urinary DLIS level. Thus, (1) urinary DLIS increases progressively during pregnancy and falls to nonpregnant values on the first postpartum day, (2) the urinary DLIS level can be related to urinary creatinine, urinary potassium, and urinary magnesium levels, and (3) when adjusted for the urinary creatinine level, the urinary calcium level relates independently to the urinary DLIS level.

DIGOXIN-LIKE IMMUNOREACTIVE SUBSTANCE AND ITS ACTIVITY IN THE NEONATE AND

The neonatal changes of digoxin-like immunoreactive substance (DLIS) in the sera from 15 preterm and 7 term infants, the immunological specificity of DLIS, and the relationship between DLIS levels and sodium excretion from the kidney were observed. The natriuretic activity of DLIS extract prepared from cord blood of healthy full-term infants by acetone-HCl extraction and a gel column was also examined by the rat renal artery perfusion method and the following results were obtained.(1) The immunological specificity and accuracy of the detection of DLIS was confirmed by a sample dilution test, a recovery test for standard digoxin, and an absorption test with antidigoxin antiserum.(2) The gestational age was smaller, the serum DLIS level was higher and there was a negative correlation between peak DLIS and gestational age (r=-0.73, P<0.001).(3) Serum DLIS levels and fractional sodium excretion (FENa). There was a statistically significant positive correlation between (r=0.35, P<0.05).(4) The injection of DLIS extracts into renal arteries of rats increased urinary sodium excretion to levels two or three times higher than that of the pre-infusion period (P<0.05).These findings led to the conclusion that DLIS might be one of the natriuretic substances in the neonatal period.

Digoxin- and digitoxin-like immunoreactive substances in amniotic fluid, cord blood, and serum of neonates.

Using four different digoxin kits, it was disclosed that the majority of various samples including amniotic fluid, cord blood, and serum from neonates contained substantial levels of digoxin-like immunoreactive substance. The differences in data seemed to be due to the range of epitopes which are recognized by antidigoxin antiserum. The day-to-day studies on sera serially obtained from infants at birth to 48 days old revealed that the level of the substance (0.31 +/- 0.12 ng/ml) in sera of the 1-day-old neonates rapidly declined to the level of 0.1 ng/ml by the 2nd postnatal wk and thereafter gradually declined. The immunological specificity and accuracy of the detection of digoxin-like immunoreactive substance was confirmed by a sample dilution test, a recovery test for standard digoxin, and an absorption test with antidigoxin antiserum. The amniotic fluid and cord blood also contained four to eight times more of a digitoxin-like immunoreactive substance than they did digoxin-like immunoreactive substance. A significant correlation was observed between the levels of digoxin-like immunoreactive substance and of digitoxin-like immunoreactive substance (p less than 0.01).