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Biomedical subjects

E V Efimova

Publications and source records attributed to E V Efimova.

At least 19 recordsLinked to original sources

[Clinical Efficacy of Combination Therapy With Trimetazidine and Angiotensin Converting Enzyme Inhibitors in Patients With Hypertension and Ischemic Heart Disease Associated With Type II Diabetes].

AIM: To assess in a randomized open study effect of 12-15 week use of angiotensin converting enzyme inhibitors (ACEI) with and without trimetazidine on myocardial perfusion reserve in patients with ischemic heart disease (IHD) and/or hypertension associated with type II diabetes. MATERIAL: Patients (n=69) receiving long term ACEI therapy with transient myocardial perfusion defects during dipyridamole stress test. METHODS: Control patients (n=29, including 15 with IHD) continued to receive an ACEI, while in trimetazidine group (n=40, including 21 IHD patients) trimetazidine (60 mg/day) was added to ACEI. Single photon emission computer tomography with (199)Thallium Chloride was used for measurement of myocardial perfusion reserve. Changes of physical working capacity, intracardiac hemodynamics and glycemia were studied only in trimetazidine group. RESULTS AND CONCLUSION: Significant 52% (mean) decrease (32.5% in IHD patients) of perfusion defects and acceleration on total clearance of Tl-199 were registered in trimetazidine group while no considerable changes of myocardial perfusion were revealed in control group. Most substantial changes of myocardial blood flow reserve occurred in patients with moderate alterations of left ventricular diastolic filling, and among IHD patients - in those without cardiac dilatation and pronounced diastolic left ventricular dysfunction. Significant increase (45.9 and 23.9% in patients with and without IHD, respectively) of total work performed during bicycle exercise was registered in trimetazidine treated patients. In IHD patients decline of initially elevated intramyocardial tension was also observed.

Angiotensin-Converting Enzyme Inhibitors↗

[Polymorphic markers of GNB3 (C825T), AGTR1 (A1166C) and ACE (A2350G and I/D) genes in patients with arterial hypertension combined with diabetes mellitus type 2].

AIM: To elicit correlations of polymorphic markers of GNB3 (C825T), AGTR1 (A1166C), ACE (A2350G and I/D) genes with arterial pressure, left ventricular hypertrophy (LVH) and blood concentrations of proinflammatory cytokines in hypertensive patients with diabetes mellitus type 2 (DM2). MATERIAL AND METHODS: Clinical parameters (24-h arterial pressure profile, echocardiographic findings, immunoenzymes level) were studied in 89 hypertensive patients with DM2. These patients had different genotypes by the studied allele variants of the genes determined by polymerase chain reaction. RESULTS: Polymorphism of A1166C gene of type 1 vascular receptor of angiotensin II (AGTR1) contributes to formation of arterial hypertension (AH) signs diversity in DM2 patients. GNB3, a gene C825T polymorphic marker, showed a correlation with diastolic arterial pressure but this variant of the gene locus is not associated with LVH. However, G-allele of ACE gene contributes much to appearance of this pathological sign. Mean values of IL-1beta and TNF-alpha as well as the presence of LVH depended on genotypes by ACE gene (polymorphism I/D). CONCLUSION: Polymorphic markers of ACE and GNB3 candidate genes influence clinical diversity of pathological signs in DM2 patients through modification of AH and LVH severity and the level of proinflammatory cytokines.

Blood Pressure↗

[Coronary flow vasodilator reserve in patients with type 2 diabetes mellitus-associated arterial hypertension].

The coronary flow vasodilator reserve (CFVR) in the proximal segment of the anterior descending coronary artery was studied in 50 patients with diabetes mellitus (DM), by Doppler study via transesophageal approach. Group 1 included 39 patients with DM concurrent with Stages 1-2 arterial hypertension (AH), of them 14 patients were documented as having coronary heart disease (CHD) in the presence of coronary atherosclerosis (Subgroup 1A) and CHD was excluded in the remaining 25 patients (Subgroup 1B). Group comprised 11 patients with normal blood pressure (BP). For comparison, 6 healthy individuals were examined. CFVR was calculated as a ratio of the peak diastolic coronary flow (CF) velocity during infusion of dipyridamole (0.56 mg/kg) to the baseline CF. CDVR was significantly decreased as compared with the controls (2.07 +/- 0.73 in Subgroup 1A, 2.15 +/- 0.67 in subgroup 1B, 1.78 +/- 0.33 in Group 2, and 3.68 +/- 0.26 in the controls), this decrease being due to low CF velocities in hyperemia in the majority of patients in Subgroup 1A and Group 2 and to higher baseline CF velocity in most patients from Subgroup 1B. In Group 1 patients, CFVR was not linear with age, the duration of the disease, BP and HbA1 levels, but it was related to the carotid distensibility coefficient (rho = 0.60, p = 0.004) and to the blood level of total cholesterol (rho = -0.43, p = 0.0107). In Group 2 patients, the least CF velocities in the presence of vasodilatation were detectable in older patients and in patients with hypercholesterolemia. An all the patients with left ventricular hypertrophy (LVH) had decreased CFVR whose values with the myocardial mass index above 130 g/m2 were significantly less than those in the absence of LVH. Thus, the limited reserve of coronary vasodilatation was detectable in patients with DM irrespective of BP levels and the status of epicardial arteries and it was most pronounced in LVH and hypercholesterolemia. The impaired elastic properties of peripheral arteries in the presence of cholesterolemia may be regarded as a marker of the low reserve of coronary vasodilatation in patients with DM concurrent with AH.

Coronary Artery Disease↗

[Effect of long term therapy with captopril on dopplerographic parameters of intrarenal blood flow and renal function in patients with hypertension and diabetes].

Effect of 9-12 month treatment with captopril on dopplerographic parameters of intrarenal blood flow and renal function was studied in 30 hypertensive diabetics without clinical signs of nephroangiopathy. There was an interrelationship between strict blood pressure (BP) control (average 24-hour BP below 135/83) and improvement of parameters of intrarenal hemodynamics. BP normalization and most pronounced positive changes of renal perfusion during therapy with captopril were achieved in patients with mild hypertension and initially high intrarenal resistance yet at the stage of normo- or microalbuminuria. In moderate hypertension with microalbuminuria treatment with captopril was associated with stabilization of parameters of renal blood flow and rate of 24-hour albumin excretion at their initial level despite less strict control of BP and unsatisfactory compensation of diabetes. BP response to captopril in patients with hypertension and diabetes was related to initial state of intrarenal hemodynamics. In patients with mild hypertension indexes of resistance of renal and intrarenal arteries could be used for prediction of sensitivity to antihypertensive action of captopril.

Adult↗

Contrasting effects of IG20 and its splice isoforms, MADD and DENN-SV, on tumor necrosis factor alpha-induced apoptosis and activation of caspase-8 and -3.

We identified a novel cDNA (IG20) that is homologous to cDNAs encoding a protein differentially expressed in normal and neoplastic cells (DENN-SV) and human MADD (MAPK-activating death domain-containing protein). Furthermore, we show that the above variants most likely result from alternative splicing of a single gene. Functional analyses of these variants in permanently transfected HeLa cells revealed that IG20 and DENN-SV render them more susceptible or resistant to tumor necrosis factor alpha (TNF-alpha)-induced apoptosis, respectively. All variants tested could interact with TNF receptor 1 and activate ERK and nuclear factor kappaB. However, relative to control cells, only cells expressing IG20 showed enhanced TNF-alpha-induced activation of caspase-8 and -3, whereas cells expressing DENN-SV showed either reduced or no caspase activation. Transfection of these cells with a cDNA encoding CrmA maximally inhibited apoptosis in HeLa-IG20 cells. Our results show that IG20 can promote TNF-alpha-induced apoptosis and activation of caspase-8 and -3 and suggest that it may play a novel role in the regulation of the pleiotropic effects of TNF-alpha through alternative splicing.

Alternative Splicing↗

[The amplification and overexpression of mdr-family genes in ethidium bromide-resistant Chinese hamster CHO-K1 cells and in the hybrids of sensitive and resistant cells].

Stable mutant cells Cebr-1 and Cebr-2, resistant to ethidium bromide (EB) in concentration of 2 micrograms/ml, have been isolated by a multistep selection in Chinese hamster ovary cells. It was shown that Cebr-1 and Cebr-2 cells acquired a cross-resistance to unrelated drugs. Stable changes in the structure of chromosomes 1, 2, 5 and 8 were revealed by karyological analysis. Overexpression and amplification of mdr genes were detected in Cebr-2 cells using Northern RNA and Southern DNA blot hybridization. Two independent hybrids Hybr-1 and Hybr-2 were obtained by fusion of Cebr-2 cells with Chinese hamster lung V-79 RJK cells, sensitive to EB. Hybr-2 cells were characterized by the same level of EB-resistance as Cebr-2 cells. Hybr-1 cells have a lower level of EB-resistance than Cebr-2 cells. Hybr-2 cells have demonstrated amplification and overexpression of mdr gene, the same as in Cebr-2 cells, whereas in Hybr-1 cells no mdr gene amplification was observed, but the level of mdr gene expression was higher than in sensitive cells. The data suggest that resistance of Chinese hamster cells to EB is mediated by amplification and overexpression of mdr genes.

Animals↗

[An increase in brain temperature in rats to the intranasal administration of thyroliberin].

The integral rat brain temperature was measured by radiothermoscope after intranasal instillation of thyroliberin in a dose 400 mkg. The recording increase of temperature lasted during two hours after instillation. This phenomenon is based both on the direct action of thyroliberin and on its capacity to stimulate the induction of other regulatory peptides.

Administration, Intranasal↗

[Thyroliberin-induced motor asymmetry as an indicator of the individual behavioral strategy of rats in a radial labyrinth].

The individual peculiarities of functional changes in motor asymmetry determined by behavioral test in T-maze have been shown in experiments with rats (nonpedigree and line LATI). The application of thyroliberin (10 mkg/kg) causes and increases the left-side lateralization which introduces alteration in the individual strategy of the successive round of 12 rays of radial maze with food during solution of spatial orientation task.

Animals↗

[Comparison of the effects of thyroliberin and ACTH4-7 PGP on the learning of rats during the solving of spatial orientation tasks].

The influence of TRH (100 micrograms/kg) and ACTH4-7 Pro-Gly-Pro (15 micrograms/kg and 25 micrograms/kg) involved an acceleration of the spatial learning on the 12-arm radial maze and on T-maze in rats; an increase in the number of correct choice after short (5-10 min) retention interval; and affected the working and reference spatial memory in the test of reinforced place performance. The effects of the TRH and ACTH4-7 Pro-Gly-Pro did not interfere with one another.

Adrenocorticotropic Hormone↗

[Early and late changes in potassium transport during the start of proliferation in CHO cell cultures. The action of serum, isoproterenol, propranolol and theophylline].

The stimulation of DNA synthesis by serum is accompanied by early (30 minutes) and late (2-8 hours) increase in ouabain-sensitive rubidium (potassium) influx and the elevation of intracellular potassium content from 0.5-0.6 to 0.7-0.8 mmole per gram protein in CHO-K1 cells. Isoproterenol alone induces the transient increase both in potassium influx via Na,K-ATPase and in potassium efflux without any effect on intracellular potassium content and cell proliferation. Isoproterenol acts synergistically with serum in eliciting the early and late changes in potassium transport and in stimulating G1----S transition. The combination of serum and theophylline produces a rapid increase in potassium influx, however, it does not stimulate DNA synthesis and does not induce any later increase in intracellular potassium content. It is concluded that early and late activation of Na,K-ATPase by mitogens can be dissociated; the Na,K-ATPase activation is involved in mitogenic response when producing the sustained potassium influx and the elevation of intracellular potassium content during G1----S transition.

Animals↗

[Cation transport and content in serum-stimulated CHO-773 cells. I. Rapid changes in rubidium and lithium influxes and intracellular sodium content].

The cultures of Chinese hamster ovary cells (CHO-K1 clone 773) can be brought to the stationary state with most of cellular populations in G1 phase by growing continuously for 4 days up to the cultural density (10-12) X 10(4) cells/cm2. Upon introduction of fresh Eagle medium with 10% calf serum the cells progress from G1 to S phase for 7-9 hours. It is shown that within the first minutes of serum addition ouabain-sensitive rubidium influx increases, however, lithium influx, which serves a test for passive sodium pathways in the membrane, increases or does not change. No correlation was found between the rubidium influx and intracellular sodium changes, induced by serum. From comparative studies of ouabain-sensitive rubidium influx, lithium influx and intracellular sodium content it is concluded that the increase in intracellular sodium is not responsible for serum-induced Na,K-ATPase activation.

Animals↗

[Cation transport and content in serum-stimulated CHO-773 cells. III. The intracellular content of sodium, calcium and magnesium].

Intracellular sodium, calcium, and magnesium content as well as lithium influx have been examined in serum-stimulated CHO cultures using flame-emission technique. Intracellular sodium and lithium influx does not change during the G1----S transition, they increase by 1.3-2 times in the late S and in mitosis. In stationary cultures of CHO cells cellular magnesium is about 50-60 mumole/gr protein; its content increases in 2-3 hours after serum addition and remains constant during the G1----S transition. In stationary cultures of CHO cells cellular calcium is about 20 mumole/gr protein and it increases by 1.5-2 times in the late G1 and S phases. It is concluded that alterations of ion transport accompany not only the early cell response to mitogen but also the G1----S transition.

Animals↗

[Karyotypic characteristics of the Chinese hamster cell line CHO-K1 resistant to colchicine].

Karyological analysis was made of G-banded chromosomes in the cells of three independent CHO-K1 clones stably resistant to colchicine (Clch) selected for resistance to Clch at the concentration 0.1 mkg/ml (the first step of selection), and of one clone with higher but unstable level of resistance (2 mkg/ml--the second level of resistance). The results obtained revealed a morphological instability of the P-shoulder of chromosome Z6: more often an additional genetical material (AGM) at the distal end (Z6+), or rarely deletions (Z6-). In cells of the stable resistant clones of the first step of selection the length of AGM and their morphological structures were shown to be constant, but differed among the clones. In cells of the higher resistant unstable clone the length of AGM and their morphological structure were different in different cells within the clone. The AGMs in the Clch-resistant cells are discussed in terms of possible amplification of gene(s) responsible for the Clch resistance. In the cell population of clone selected for the resistance to 2 mkg/ml of Clch the frequency of rearranged chromosomes was shown to increase. In cells of all the analysed resistant clones the chromosome Z16 was found to lose its p-shoulder.

Animals↗

[Isoproterenol stimulation of the repair of single-stranded DNA breaks in Chinese hamster cells induced by gamma irradiation].

The action of the increased intracellular content of adenosine monophosphate (cAMP) in CHO-K1 cells (clones 773 and ADr112eb), treated with isoproterenol, on gamma-induced DNA single-strand breaks repair has been investigated. The hormonal treatment stimulates gamma-induced (180 Gr) DNA single-strand repair during the post-irradiation incubation (45 min) by 75 +/- 16%. The results show the involvement of the cAMP system in radiosensitivity of cultured mammalian cells and in regulation of cellular mechanisms of DNA repair.

Animals↗

[Cyclic adenosine monophosphate content and its regulatory characteristics in Chinese hamster cells with genetically determined changes in the cell surface].

The intra- and extracellular concentrations of cyclic adenosine monophosphate (cAMP) in cell line CHO-K1, sensitive (clone 773) and resistant to cytotoxic action of ethidium bromide (EBr), colchicine (Cr) and actinomycin D (ADr), as well as the amount of cAMP in response to isoproterenol, 10% serum and ethidium bromide (EB) in these cells were studied. The increased level of cAMP in EBr- and, Cr-cells, and the decreased one--in ADr cells was found as compared with sensitive cells. The amount of cAMP extruded in the surrounding medium was lower for EBr- and Cr-cells and higher for ADr-cells, in comparison with sensitive cells. All the variants of resistant cells were characterized by a less intensive but a longer reaction for isoproterenol, as compared with sensitive cells. In all the investigated variants 10% serum induced a remarkable increase in the intracellular cAMP by the 2nd hour after their insignificant decrease. 1 mcg/ml concentration of EBr increased intracellular cAMP only in 773-cells. The rules changing the cAMP level to isoproterenol and EB2; are determined by differences in reaction of adenylate cyclase, as it has been demonstrated for the 773- and EBr-cells.

Animals↗

[Genetic characteristics of Chinese hamster cell resistance to colchicine, actinomycin D and ethidium bromide].

We have tried to study genetics of Chinese hamster cellular drug resistance to colchicine, actinomycin D and ethidium bromide. Resistant variants arising at a frequency 10(-5) to 10(-7) were selected from a sensitive population. Pretreatment with MNNG increased this frequency 106, 9-15, 12-26 times for colchicine, actinomycin D and ethidium bromide, respectively. Fluctuation test analysis allows to suppose that phenotypic expression of drug resistance is genetically determined and resulted from random genetical events. Significant values of particular correlation coefficients for selecting resistant variants in a set of independently originated subpopulations suggest the genetical identity of the majority of variants selected by colchicine and actinomycin D. At the same time, the significant portion of colchicine-resistant cells may be selected using ethidium bromide. It is not unlikely that under above experimental conditions, each selective agent reveals genetically different resistant variants. The possible genetic mechanisms of resistance to the drugs used are discussed.

Animals↗