[Treatment of patients with hearing functional system impaired as a result of explosion barotraumas].
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Adolescent↗
Biomedical subjects
O V Fedorova
Publications and source records attributed to O V Fedorova.
[A variant of monotherapy in vertigo and subjective noise in the ears].
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Adult↗
Interaction of NaCl and behavioral stress on endogenous sodium pump ligands in rats.
Our study investigated the hypothesis that the combination of a high NaCl diet and social isolation stress would increase systolic blood pressure (SBP) and endogenous sodium pump ligands (SPL), ouabainlike compound (OLC), and marinobufagenin (MBG). Excretion of MBG and OLC, SBP, and organ weights were studied in four groups (n = 8) of male Fisher 344 x Norwegian brown rats: controls, socially isolated (Iso), 4% NaCl diet (Salt), and the combination of Salt and Iso (Iso+Salt). In Salt, MBG excretion increased by 78% (P < 0.01), whereas SBP and OLC remained unchanged. In Iso, SBP and MBG did not change, but OLC peaked on day 1. In the Iso+Salt, SBP increased by 9 mmHg, MBG excretion increased (42.0 +/- 7.6 vs. 10.0 +/- 1.5 pmol/24 h, P < 0.01), whereas OLC peaked at day 1 (25.0 +/- 2.5 vs. 10.0 +/- 2.0 pmol/24 h, P < 0.01) and remained elevated. Heart and kidney weights were increased in Salt and Iso+Salt. Aortic weights were increased in Iso and Iso+Salt. Thus a high NaCl intake stimulates MBG excretion, whereas isolation stress stimulates OLC. The combination of Salt and Iso is accompanied by marked stimulation of both SPL.
Animals↗
Marinobufagenin, an endogenous alpha-1 sodium pump ligand, in hypertensive Dahl salt-sensitive rats.
Dahl salt-sensitive rats (DS), which have a mutation in the alpha-1 subunit of Na(+)/K(+)-ATPase, exhibit impaired pressure natriuresis and on a high-salt diet, retain Na(+) and exhibit increased blood pressure. Recently, we have shown that mammalian tissues contain a bufadienolide Na(+)/K(+)-ATPase inhibitory factor, marinobufagenin (MBG), that exhibits greater affinity for the alpha-1 than alpha-3 sodium pump isoform. The present study investigated the possible role of MBG in hypertension in DS on a high NaCl intake. Eight DS and 8 Dahl salt-resistant rats (DR) were placed on an 8% NaCl diet. Within 2 weeks, systolic blood pressure increased in DS (162+/-9 mm Hg at week 2 versus 110+/-2 mm Hg in baseline, P<0.01), and increased less in DR (124+/-3 mm Hg at week 2 versus 112+/-2 mm Hg in baseline). Renal excretion of MBG increased 4-fold (38.9+/-7.6 pmol versus 9.1+/-1.3 pmol in baseline, P<0.01) in DS, but by only 25% in DR (13.2+/-0.9 pmol versus 10.3+/-0.7 pmol in baseline). Excretion of endogenous ouabain did not change in either strain. MBG-immunoreactive material was purified from the urine of hypertensive DS by means of 2 steps of reverse-phase high performance liquid chromatography (HPLC) and compared with plant ouabain and amphibian MBG for its ability to inhibit the Na(+)/K(+)-ATPase from rat kidney (which expresses only alpha-1 Na(+)/K(+)-ATPase isoform). Unlike ouabain (IC(50)=248 micromol/L), serially diluted, HPLC-purified MBG immunoreactivity from DS and authentic MBG potently inhibited rat kidney Na(+)/K(+)-ATPase (IC(50)=70 and 78 nmol/L, respectively). Our results suggest that an alpha-1 Na(+)/K(+)-ATPase ligand, MBG, is elaborated to promote natriuresis in hypertensive DS. MBG acts as a selective inhibitor of the ouabain-resistant alpha-1 Na(+)/K(+)-ATPase subunit, ie, the major sodium pump isoform of the kidneys, as would be expected of a putative natriuretic hormone.
Animals↗
Endogenous Na,K pump ligands are differentially regulated during acute NaCl loading of Dahl rats.
BACKGROUND: Two mammalian digitalis-like factors, an ouabain-like compound (OLC) and marinobufagenin (MBG), exhibit specificity to alpha-3 and alpha-1 Na(+),K(+)-ATPase isoforms, respectively. We compared regulation of MBG and OLC by acute NaCl loading in Dahl salt-sensitive (DS) and salt-resistant (DR) rats. METHODS AND RESULTS: An intraperitoneal NaCl load (0.8 g/kg) was given to adult male rats (24 DS and 24 DR). Diuresis, natriuresis, renal excretion, and tissue levels of MBG and OLC were measured. Inhibition of renal Na(+),K(+)-ATPase by MBG and ouabain was compared in DS, DR, and Wistar rats. DS (versus DR) exhibited a smaller peak (2 hours) natriuretic response (1.34+/-0.10 versus 2.08+/-0.14 mmol. kg(-)(1). h(-)(1); P:<0.01), despite a greater plasma Na(+) (153+/-2 versus 145+/-1 mmol/L; P:<0.01). In DS and DR, pituitary, adrenal, and plasma OLC exhibited transient 2-fold to 3-fold increases, followed by a decrease to baseline levels. Plasma and adrenal MBG doubled in both strains within 1 hour of NaCl loading and remained elevated. Eight-hour MBG excretion in DS was 4-fold greater than in DR (15. 8+/-0.8 versus 3.6+/-0.4 pmol; P:<0.01), whereas OLC excretion in DS was only 30% greater than in DR (16.1+/-1.1 and 11.9+/-0.8 pmol; P:<0.05). Kidney Na(+),K(+)-ATPase (alpha-1 isoform) from Wistar rats and DS exhibited greater sensitivity to MBG than to ouabain. CONCLUSIONS: NaCl loading of DS causes transient increase in OLC but sustained increases in MBG tissue levels and excretion. We hypothesize that increased MBG production occurs in an attempt to compensate for genetically impaired pressure-natriuresis mechanisms.
Animals↗
Cicletanine reverses vasoconstriction induced by the endogenous sodium pump ligand, marinobufagenin, via a protein kinase C dependent mechanism.
RATIONALE: Cicletanine (CIC), an anti-hypertensive compound with direct vascular and natriuretic actions, is especially effective in salt-sensitive hypertension, in which dysregulation of the sodium pump plays an important pathogenic role, and digitalis-like cardiotonic steroids contribute to increased vascular tone. The purpose of the present study was to investigate whether, and by what mechanisms, cicletanine antagonizes the vasoconstrictor effects of cardiotonic steroids in isolated human arteries. METHODS: The effects of cicletanine on vascular tone were studied in isolated, endothelium-denuded rings of 2nd-3rd-order branches of human mesenteric arteries pre-contracted with bufodienolide marinobufagenin (MBG), an Na/K-ATPase inhibitor, or endothelin-1 (ET-1). Na/K-ATPase activity was measured in sarcolemmal membranes from the mesenteric artery. Activity of rat brain protein kinase C (PKC) was measured using the PepTag phosphorylation assay. RESULTS: MBG and ET-1 both induced sustained vasoconstriction in human mesenteric artery rings, and cicletanine relaxed rings pre-contracted with either MBG (EC50 = 11 +/- 2 micromol/l) or ET-1 (EC50 = 6.4 +/- 1.1 micromol/l). Although 8-Br-cGMP (100 micromol/l) caused complete vasorelaxation of arterial rings pre-contracted with ET-1, it did not affect the MBG-induced vasoconstriction. An activator of PKC, phorbol diacetate (PDA) (50 nmol/l), attenuated CIC-induced vasorelaxation of mesenteric artery rings pre-contracted with MBG (EC50 > 100 micromol/l), but not rings pre-contracted with ET-1 (EC50 = 6.5 +/- 1.2 micromol/l). In mesenteric artery sarcolemma, 100 nmol/l MBG inhibited the Na/K-ATPase by 68 +/- 5% and cicletanine (100 micromol/l) attenuated this Na/K-ATPase inhibition by 85 +/- 6%. In the PepTag PKC assay, cicletanine produced a concentration-dependent inhibition of rat brain PKC activity (IC50 45 +/- 11 micromol/l). In the presence of 50 nmol/l PDA, 100 micromol/l cicletanine did not antagonize the Na/K-ATPase inhibition by MBG, and did not inhibit the PKC from rat brain. CONCLUSIONS: Cicletanine antagonizes vasoconstriction induced by Na/K-ATPase inhibition via a PKC-dependent mechanism that does not involve inhibition of cyclic GMP phosphodiesterase (cGMP-PDE). This mechanism of action may be relevant to the greater potency of cicletanine in salt-sensitive hypertension in which plasma levels of endogenous digitalis-like cardiotonic steroids are elevated. Our findings also suggest that PKC is an important factor for cardiotonic steroid-Na/K-ATPase interactions on the vascular tone, and is therefore a potential target for therapeutic intervention in hypertension.
Animals↗
[Diagnostic criteria and treatment strategies in traumatic injuries of the ear].
The paper presents the results of examination and treatment of patients with different traumatic injuries of ear structures. The most characteristic injuries were detected in different mechanisms of traumas: mechanical (direct, indirect), altitude-induced, and thermal injuries. Major diagnostic signs of traumatic perilymphatic fistulas were revealed. The efficiency of surgical treatment for different injuries was evaluated. The surgical management of traumatic perilymphatic fistulas was comparatively assessed in different periods following injury. Evidence is provided for that it is expedient to close perilymphatic fistulas in ear injuries as early as possible.
Adolescent↗
Circulating bufodienolide and cardenolide sodium pump inhibitors in preeclampsia.
OBJECTIVE: To determine plasma levels of the endogenous bufodienolide Na+/K+ ATPase inhibitor, marinobufagenin-like factor (MBG), in normotensive pregnancy and in preeclampsia, to compare changes of MBG with that of ouabain-like compound (OLC), and to characterize the purified MBG immunoreactive factor from preeclamptic plasma. DESIGN AND METHODS: Consecutive sample study. The levels of MBG and OLC compounds were measured in extracted plasma by solid phase fluoroimmunoassays. MBG and ouabain immunoreactive materials were partially purified from preeclamptic plasma via reverse-phase high-performance liquid chromatography (HPLC) and studied for their ability to cross react with MBG and ouabain antibodies, and to inhibit the Na+/K+ ATPase from human mesenteric arteries. Vasoconstrictor effect of authentic MBG was studied in isolated rings of human umbilical arteries. RESULTS: In 11 nonpregnant control individuals, plasma concentrations of MBG and OLC were 0.190+/-0.04 nmol/l and 0.297+/-0.037 nmol/l, respectively. In the third trimester of noncomplicated pregnancy (n = 6), plasma MBG increased (0.625+/-0.067 nmol/l, P<0.05), and OLC did not (0.32+/-0.07 nmol/l). In 15 patients with preeclampsia, plasma levels of both MBG and OLC increased dramatically (2.63+/-0.10 nmol/l and 0.697+/-0.16 nmol/l, respectively, P<0.01 versus both control groups). When fractionated by reverse phase HPLC, OLC was eluted by 18% acetonitrile, and MBG by 48% acetonitrile. Serially diluted samples of MBG and OLC immunoreactive materials from HPLC fractions reacted with MBG and ouabain antibody in solid phase immunoassay in a concentration dependent fashion. Authentic MBG caused contractile responses of isolated rings of human mesenteric arteries in a concentration-dependent manner. Similarly to the authentic MBG, HPLC purified MBG immunoreactive material from preeclamptic plasma inhibited Na+/K+ ATPase purified from human mesenteric artery. CONCLUSIONS: Our observations demonstrate the coexistence of two endogenous cardiotonic steroids in preeclamptic plasma, a more polar OLC and a less polar MBG-like compound. Substantial increases in plasma OLC and MBG immunoreactivity in preeclampsia, along with the vasoconstrictor properties of authentic MBG and Na+,K+ ATPase inhibitory activity of human MBG immunoreactive factor, suggest, that in preeclampsia, plasma concentrations of MBG are enough to substantially inhibit the sodium pump in cardiovascular tissues, and are in accordance with the views attributing endogenous digitalis-like factors a pathogenic role in the preeclamptic hypertension.
Adult↗
[The rehabilitation of patients with perilymphatic fistulae of the labyrinth].
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Adult↗
Plasma marinobufagenin-like and ouabain-like immunoreactivity in adrenocorticotropin-treated rats.
Recently, an endogenous digitalis-like factor (EDLF) was shown to be stimulated in corticotropin (ACTH) hypertension in the rat. We have shown that mammalian plasma contains a vasoconstrictor Na,K-ATPase inhibitor, which cross-reacts with an antibody to amphibian EDLF, marinobufagenin. In the present experiment, the effect of 8 days of intramuscular ACTH treatment (0.5 mg/kg/day) of male Fisher 344 x NB rats on blood pressure, plasma ouabain-like and marinobufagenin-like immunoreactivity, and on the activity of Na,K-ATPase in aortic sarcolemma were studied. The ACTH treatment for 8 days resulted in increased systolic blood pressure (151 +/- 12.4 v 121 +/- 4.0 mm Hg, P < .01), inhibition of Na,K-ATPase in aortic sarcolemma (2.99 +/- 0.35 v 5.43 +/- 0.17 micromol ADP/mg(prot)/h), and increases in plasma concentration of marinobufagenin-like (0.44 +/- 0.06 v 0.21 +/- 0.05 nmol/L), but not ouabain-like (0.09 +/- 0.01 v 0.10 +/- 0.04 nmol/L) immunoreactivity. In dissociation enhanced lanthanide fluoroimmunoassay (DELFIA), serial dilutions of plasma from ACTH-treated rats extracted with 25% and 80% acetonitrile, respectively, demonstrated parallelism to the calibration curves of ouabain and marinobufagenin. These findings suggest that an endogenous bufodienolide Na,K-ATPase inhibitor, rather than an endogenous ouabain-like compound, is increased after 8 days of treatment of rats with ACTH.
Adrenocorticotropic Hormone↗
Effects of two putative endogenous digitalis-like factors, marinobufagenin and ouabain, on the Na+, K+-pump in human mesenteric arteries.
OBJECTIVES: Recently, in rat aortae, two putative digitalis-like factors, marinobufagenin and ouabain, were shown to interact with alpha-1 (sarcolemma) and alpha-3 (nerve endings) subunits of the sodium pump, respectively, and elicit vasoconstriction via inhibition of the Na+,K+-pump in vascular smooth muscle or norepinephrine release. The purpose of the present study was to investigate the effects of ouabain and marinobufagenin on vascular tone, activity of Na+,K+-pump, and the expression of isoforms of the Na+,K+-ATPase alpha-subunit in human mesenteric arteries. DESIGN AND METHODS: Arteries were obtained from male patients undergoing surgery due to intestinal adenocarcinoma. Vasoconstrictor effects of both inhibitors were studied in isolated vascular rings. Na+,K+-pump activity was measured using the 86Rb technique. Membrane fractions of sarcolemma and nerve endings plasmalemma were prepared via differential centrifugation of membranes in a sucrose density gradient Specific antibodies to the alpha-1 and alpha-3 subunits of Na+,K+-ATPase were used to detect alpha-1 and alpha-3 isoforms in the membrane fractions by Western blotting. RESULTS: Marinobufagenin (EC50 = 88+/-15 nmoles/l) and ouabain (EC50 = 320+/-50 nmoles/l) elicited vasoconstriction in mesenteric artery rings. At a concentration of 1 nmol/l, both compounds stimulated the Na+,K+-pump, but inhibited its activity at 10-1000 nmoles/l. No stimulation of the Na+,K+-pump was observed in the presence of 5 micromol/l phentolamine; rather 1 nmol/l of marinobufagenin and ouabain inhibited the Na+,K+-pump by 30% and 13%, respectively. The alpha-1 polyclonal antibody detected alpha-1 isoform in membrane fractions from both sarcolemma and nerve endings. A monoclonal alpha-1 antibody detected the material in sarcolemmal membranes only. The alpha-3 isoform was detected in both membrane fractions by both antibodies, but staining for alpha-3 was more pronounced in the nerve endings. CONCLUSIONS: These results demonstrate that, in physiologically 'realistic' concentrations, marinobufagenin and ouabain can significantly affect the Na+,K+-pump in human mesenteric artery, and illustrate the importance of interaction of digitalis-like Na+,K+-pump inhibitors with the Na+,K+-ATPase localized to the intravascular adrenergic terminals. Present observations are in accord with the previous data suggesting that marinobufagenin and ouabain display greater affinity to alpha-1 and alpha-3 isoforms of the Na+,K+-pump, respectively, and support the view that the differential responsiveness to endogenous digitalis-like inhibitors is one of the features of alpha-isoforms of Na+,K+-ATPase.
Animals↗
Characterization of a urinary bufodienolide Na+,K+-ATPase inhibitor in patients after acute myocardial infarction.
Recent evidence suggests the existence of several endogenous Na+,K+-ATPase inhibitors in mammals. Previously, we have shown that the amphibian Na+,K+-ATPase inhibitor marinobufagenin (3,5-dihydroxy-14,15-epoxy bufodienolide) acts as a vasoconstrictor in isolated rat and human arteries. Mammalian plasma was shown to contain marinobufagenin-like immunoreactive material, which is responsive to saline volume expansion. The present study describes purification of a bufodienolide, which is similar to marinobufagenin, from the urine of patients after acute myocardial infarction with the use of thin-layer chromatography and reverse-phase high-performance liquid chromatography (HPLC). The purified substance cross-reacted with marinobufagenin antibody, demonstrated maximal UV absorbance at 300 nm characteristic of bufodienolides, and eluted from HPLC columns with the same retention time as marinobufagenin. Mass spectrometry of purified material revealed the presence of a substance indistinguishable from amphibian marinobufagenin and having molecular mass of 400 D. The present studies show that one of the human digitalis-like factors may have a bufodienolide structure and is likely to represent marinobufagenin or its isomer, and they suggest a role for this substance in the pathogenesis of myocardial ischemia.
Acute Disease↗
[Injury-dependent types of damage to ear structures].
The paper presents analysis of clinical and operative findings in patients with different ear lesions. Most typical signs of structural damage in relation to trauma mechanism, optimal time and indications to explorative tympanotomy, efficacy of relevant treatment in the surdological departments are described.
Adolescent↗
Inhibition of Na/K ATPase from rat aorta by two Na/K pump inhibitors, ouabain and marinobufagenin: evidence of interaction with different alpha-subunit isoforms.
Recently, we have shown that mammalian plasma cross-reacts with an antibody to a bufodienolide Na/K ATPase inhibitor, marinobufagenin. In rat aorta, marinobufagenin induced vasoconstriction via inhibition of the vascular smooth muscle Na/K pump, whereas ouabain had its predominant effect on pumps localized to nerve endings. Na/K ATPase inhibitory effects of ouabain and marinobufagenin were studied in two membrane fractions isolated from Fisher 344xBN rat thoracic aorta by sucrose density gradient centrifugation. One fraction contained predominantly the alpha-3 isoform of Na/K ATPase and represented membranes from the perivascular nerve endings (neuronal plasmalemma). The other membrane fraction, containing predominantly the alpha-1 isoform, was derived from the vascular smooth muscle sarcolemma. The IC50 for inhibition of the Na/K ATPase by ouabain and marinobufagenin were 2.6 nmol/L and 0.14 micromol/L in the neuronal plasmalemma, and 50 nmol/L and 2.1 nmol/L in sarcolemma, respectively. These results confirm the view that differential responsiveness to endogenous digitalis-like factors is a functional feature of alpha isoforms of Na/K ATPase.
Animals↗
Endogenous marinobufagenin-like immunoreactive substance. A possible endogenous Na, K-ATPase inhibitor with vasoconstrictor activity.
Vasoconstrictor and Na/K pump inhibitory properties of a bufodienolide Na/K-ATPase inhibitor, marinobufagenin, were studied in isolated rings of 2 to 3 order branches of human pulmonary arteries respectively. Marinobufagenin displayed concentration-dependent vasoconstrictor activity (0.01 to 10 mmol/L). In sarcolemma membranes prepared from pulmonary artery marinobufagenin inhibited Na/K-ATPase (IC50 = 50 nmol/L). In eight healthy male Caucasians, concentrations of marinobufagenin-like immunoreactive material in C-18 extracted plasma were 1.38 +/- 0.60 nmol/L. Twenty-four-hour urinary release of marinobufagenin-like immunoreactive material in eight healthy males was 1.20 +/- 0.95 nmol/day. Chloroform extract of human urine was fractionated using reverse-phase high-performance liquid chromatography (32% acetonitrile, Deltapak). The HPLC fraction coeluting with marinobufagenin in 7 min, cross reacted with antimarinobufagenin and antidigoxin, but not antiouabain antibody. These results demonstrate that human plasma and urine contains a bufodienolide vasoconstrictor EDLF, marinobufagenin-like immunoreactive Na,K pump inhibitor.
Bufanolides↗
Inhibition of erythrocyte Na,K-ATPase activity during anticipatory hypoventilation in micropigs.
Previous studies with micropigs showed that conditioned suppression of respiration preceding the onset of an avoidance task was associated with increased pCO2, decreased plasma pH, decreased hematocrit, and increased blood pressure with no change in heart rate. Voluntary hypoventilation by humans, which evoked similar effects, was found to elicit increases in plasma endogenous digitalis-like factors (EDLF) and decreases in erythrocyte Na,K-ATPase. The present study investigated plasma EDLF and Na,K-ATPase activity in micropigs preceding and during avoidance sessions. Compared with levels in a controlled environment, 1 h of quiet waiting for the onset of a 30-min avoidance task was associated with hypoventilation, acidification of the plasma, and a decrease in hematocrit with progressive increases in plasma EDLF, and decreased in erythrocyte Na,K-ATPase activity (1.67 +/- 0.35 v 2.73 +/- 0.24 mumol Pi/mL er/h). Systolic blood pressure increased (126.5 +/- 5.7 v 121.7 +/- 4.2 mm Hg) during preavoidance periods, with no changes in heart rate (89.5 +/- 3.9 v 89.4 +/- 4.0 beats/min). During the avoidance sessions, plasma EDLF, systolic blood pressure (126.7 +/- 4.5 mm Hg), and heart rate (107.3 +/- 4.8 beats/min) were elevated above the first 10 min of preavoidance, whereas Na,K-ATPase activity returned toward control values (2.46 +/- 0.83 mumol Pi/mL er/h). These findings are consistent with the view that elevation of blood pressure during behaviorally induced hypoventilation in micropigs is mediated in part by inhibition of Na,K-ATPase by increases in plasma EDLF due to expanded plasma volume.
Animals↗
Plasma marinobufagenin-like and ouabain-like immunoreactivity during saline volume expansion in anesthetized dogs.
OBJECTIVES: This study investigated effects of acute plasma volume expansion on plasma levels and urinary output of two endogenous Na,K-ATPase inhibitors, marinobufagenin-like and ouabain-like immunoreactive substances. METHODS: Plasma volume was expanded for 3 h via intravenous saline infusion in three groups of anesthetized dogs--nontreated (n = 5); pretreated with rabbit antidigoxin (n = 5); and pretreated with rabbit antimouse (control) antibody (n = 4). RESULTS: Plasma marinobufagenin-like immunoreactivity increased to 11.87 +/- 3.16 nmol.l-1 (vs. 0.30 +/- 0.16 nmol.l-1) within 10 min of volume expansion, in parallel with a 15% increase in LVdP/dt, then decreased to 2.21 +/- 0.59 nmol.l-1, and in 90 min increased to 11.8 +/- 2.8 nmol.l-1, in parallel with the maximal natriuretic response. Plasma concentrations of ouabain-like immunoreactive material were increased after 90 min of saline infusion (0.019 +/- 0.004 nmol.l-1 vs. 0.139 +/- 0.056 nmol.l-1). Pretreatment of the animals with antidigoxin antibody blocked the positive inotropic and reduced natriuretic response to volume expansion, and decreased the urinary release of marinobufagenin-like, but not ouabain-like, material. CONCLUSIONS: These results show the presence of marinobufagenin-like immunoreactive substance in dog plasma and suggest that mammalian EDLF may have a bufodienolide nature. Endogenous marinobufagenin-like immunoreactive substance, which is likely to cross-react with antidigoxin antibody, is involved in the natriuretic and positive inotropic responses to plasma volume expansion.
Animals↗