[Potentialities of tissue dopplerechocardiography in diagnosis of diastolic left ventricular dysfunction in coronary heart disease (review)].
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Biomedical subjects
Publications and source records attributed to A V Lebedev.
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Eukaryotic and viral messenger RNAs contain a CAP structure that plays an important role in the initiation of translation and several other cellular processes that involve mRNAs. In this paper, we report a convenient chemical approach to the preparation of milligram quantities of short, capped RNA oligonucleotides, which overcomes some of the limitations of previous approaches. The method is based on the use of a reactive precursor, m7GppQ [P1-7-methylguanosine-5'-O-yl, P2-O-8-(5-chloroquinolyl) pyrophosphate]. The precursor reacts smoothly with 5'-phosphorylated unprotected short RNA in the presence of CuCl2 in organic media. The feasibility of this approach was demonstrated by the synthesis of the capped pentaribonucleotide m7GpppGpApCpU. The synthesized capped oligonucleotide was isolated and purified by reverse phase and ion exchange HPLC with a final yield of 37%. The structure of the m7GpppGpApCpU was confirmed by 31P NMR, mass-spectrometry and enzymatic hydrolysis.
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Antioxidant properties of 2,3,5,7,8-pentahydroxy-6-ethyl-1,4-naphthoquinone (echinochrome A) were linked with the scavenging of peroxy radicals in liposomes, trapping of superoxide anion radicals, and binding of ferrous ions to inactive complexes in the aqueous phase. The antioxidant property of 6-ethyl-2,3,7-trimethoxy-5,8-dihydroxy-1,4-naphthoquinone (trimethoxyechinochrome A) was negligible. Autooxidation of echinochrome A was increased in basic media according to the degree of its dissociation. Autooxidation of polyvalent anions in basic media was accompanied by generation of naphthosemiquinone and superoxide anion radicals as free radical intermediates. An increased rate of echinochrome A autooxidation was noted in the presence of calcium ions. This was explained by a shift of pK of Ca2+-echinochrome A complexes toward acidic pH comparably with echinochrome A. Echinochrome A possessed pronounced mutagenic activity, while trimethoxyechinochrome A was inactive in the Salmonella/mammalian microsome reverse mutation assay (Ames test) for all examined cells (TA98, TA100, TA1537). Comparison of the chemical and biological activity of echinochrome A and trimethoxyechinochrome A demonstrated the key role of the beta-hydroxyl groups in the 2nd, 3rd, and 7th naphthol cycle positions. The O2-* and naphthosemiquinone radicals generated in the redox transition of 2,3-oxygroups may be the reason for the strongly pronounced mutagenicity of echinochrome A.
AIM: To study hemodynamic effects of replacement hormone therapy (RHT) with trisecvens, beta-blocker betaksolol and their combination in perimenopausal and menopausal women with hypertension. MATERIAL AND METHODS: The study was made of 60 menopausal women aged 45-60 with mild and moderate arterial hypertension (AH). The women had no contraindications to either RHT or beta-blockers. They were randomized into three groups: group 1 received trisekvens, group 2--trisekvens plus betaksolol in a dose 10-20 mg/day, group 3--betaksolol. Arterial pressure (AP) and heart rate (HR) were measured before the treatment, in one month and each three months for a year. ECG and echo-CG were registered before treatment and each 3 months of the therapy. AP monitoring covered 50% of the patients of each group before the treatment and after 1 and 3 months of it. The data were analysed according to SAS system. RESULTS: Group 1 patients showed no significant changes in AP and HR. Group 2 and 3 patients' AP lowered, in group 2 the fall of systolic AP being more pronounced. 12-month therapy brought about a 10.3% decrease in left ventricular myocardial mass index in group 2. CONCLUSION: RHT with trisekvens in combination with beta-blocker in long-term use potentiates the effect on systolic AP and reduced hypertrophy of the left ventricle. RHT does not produce a significant effect on AP in women with AH recorded before the menopause.
Six corticosteroids were measured by high performance microcolumn reverse-phase liquid chromatography in patients with the depressive syndrome and depersonalization. Changes in the blood concentrations of hydrocortisone, cortisone, and corticosterone were revealed. The method is recommended as an additional tool for the differential diagnosis of depressions and depersonalization.
AIM: To compare in the non-blind randomised parallel study the efficiency of quadropril and amlodipine in the treatment of mild to moderate arterial hypertension. MATERIAL AND METHODS: A total of 80 patients (57.6 +/- 1.0 years) were included in this study. The patients were randomised in two groups, 40 patients each. Patients of group 1 received monotherapy with quadropril, while those of group 2 were treated with amlodipine. The treatment duration was 8 weeks in both groups. Quadropril was given in a fixed dose of 6 mg once daily. The initial dose of amlodipine was 5 mg/day. In case of insufficient effect the dose was elevated to 10 mg/day. The efficacy was evaluated by changes in blood pressure (BP) measured at rest. Moreover, in 50 randomly chosen patients 24-h monitoring of BP was performed at the start and end of the treatment. RESULTS: In the quadropril group baseline systolic BP reached 158.6 +/- 2.1 mm Hg, diastolic BP--101.8 +/- 0.8 mm Hg, heart rate was 74.3 +/- 1.6 beats/min. In the amlodipine group baseline systolic BP was 159.9 +/- 2.4 mm Hg, diastolic BP--101.8 +/- 1.0 mm Hg, heart rate was 71.3 +/- 1.0 beats/min. Systolic BP decreased at the end of quadropril therapy to 138.5 +/- 2.2 mm Hg, diastolic BP to 88.1 +/- 1.4 mm Hg. No significant change of the heart rate was observed. Under 5 mg of amlodipine systolic BP decreased to 137.9 +/- 2.5 mm Hg and diastolic BP to 87.1 +/- 1.6 mm Hg. Heart rate increased to 73.3 +/- 2.2 beats/min. Under therapy with 10 mg amlodipine systolic BP decreased to 145.9 +/- 3.8 mm Hg, diastolic BP to 89.7 +/- 3.4 mm Hg. Heart rate increased to 77.3 +/- 4.0 beats/min (p < 0.01). The hypotensive effect of quadropril remained stable while the effect of amlodipine decreased by the 8th week of therapy (p < 0.01). Side effects were observed significantly more often in the amlodipine group, then in the quadropril group. The main quadropril side effect was cough. Side effects observed in the amlodipine group were edemas, tachycardia, weakness. CONCLUSION: Both quadropril and amlodipine demonstrated a comparable antihypertensive effect although in 11 of 40 patients in the amlodipine group a dose increase was necessary and tolerability of quadropril was better.
AIM: The study of hypotensive efficacy of high-cardioselective beta-blocker betaxolol, its effects on lipid and carbohydrate metabolism, menopausal syndrome in females with mild and moderate arterial hypertension. MATERIALS AND METHODS: 20 postmenopausal 45-59-year-old women entered the trial of betaxolol. They had diastolic blood pressure 90-114 mm Hg. Beta-blockers were not contraindicated. Arterial pressure, heart rate, body mass, blood lipid spectrum, glucose and insulin levels were evaluated before the treatment, 1, 3 and 6 months after it. RESULTS: Betaxolol safely and effectively lowered blood pressure. Blood lipid spectrum remained unchanged. A transitory rise in fasting insulin levels did not worsen glucose tolerance despite a small gain in body mass. Menopausal syndrome relieved due to good effect of betaxolol on vasomotor disorders. CONCLUSION: Betaxolol has a good hypotensive effect in the absence of adverse effects on lipid and carbohydrate metabolism. A reduction of menopausal syndrome was also achieved.
The interaction of natural polyhydroxy-1,4-naphthoquinones (PHNQ) with superoxide anion-radical (O2) was studied by UV--visible spectrophotometry. 3-Acetyl-2,6,7-trihydroxynaphthazarin (spinochrome C), 2,3,7-trihydroxynaphthazarin (spinochrome D), 2,3,6, 7-tetrahydroxynaphthazarin (spinochrome E), 6-ethyl-2,3, 7-trihydroxynaphthazarin (echinochrome A), 6-ethyl-2,3, 7-trimethoxynaphthazarin (trimethoxyechinochrome A), and 2, 3-dihydroxy-6,7-dimethylnaphthazarin (A618) were tested. Xanthine and xanthine oxidase were used to generate **O2. The interaction with O2 led to significant time-dependent changes in the spectra of echinochrome A and spinochromes D and E. There was a weak influence of O2 on the spinochrome C spectrum and no change in the trimethoxyechinochrome A spectrum. The spectra that were transforming during the time of the reaction contained a pronounced isobestic point. This indicates that a single reaction product is being formed. We suggest that 1,2,3,4-tetraketones are formed from 2, 3,5,8-tetrahydroxy-1,4-naphthoquinones (echinochrome A and spinochromes D and E) via O2-induced oxidation of their OH-groups in the 2nd and 3rd positions. Reaction constants were determined by a competitive method using nitro blue tetrazolium (NBT). The reaction constants were about 104-105 M-1.sec-1. They decreased in the sequence: echinochrome A > spinochrome D > spinochrome C > NBT > trimethoxyechinochrome A. Thus, we conclude that some of the natural PHNQ containing hydroxyl groups in the 2nd and 3rd positions may act as powerful superoxide anion-radical scavengers.
A series of hydroxynaphthazarins has been synthesized. Some of them were found in in vivo experiments to be protectors of myocardium under ischemia-reperfusion and to reduce the infarction zone by 50% without any adverse effect. All compounds exhibit a moderate or small toxicity and are active in low doses.
AIM: The study of the effects of the inhibitor of angiotensin converting enzyme ramipril (tritace) on the 24-h profile of blood pressure (BP) in patients with mild and moderate arterial hypertension. MATERIALS AND METHODS: Ramipril was given to 21 males aged 45-68 years with essential hypertension stage II (WHO criteria) with stable elevated diastolic blood pressure (95-114 mm Hg) in a single dose 2.5-10 mg/day. Captopril controls received 100 mg twice a day. BP was monitored using "SpaceLabs Medical" unit (model 90207, USA). RESULTS: Compared to placebo, ramipril lowered systolic and diastolic blood pressure both for the 24-h period and in the day time; captopril lowered only diastolic BP in the day time. Side effects of long-term application of ramipril occurred 2 times less frequently than in application of captopril. CONCLUSION: Long-term treatment with ramipril in the above regimen provides more effective control of BP than captopril in the above doses in patients with mild and moderate hypertension.
New pyranone derivatives having tri- or pentamethylenamine linker functions were synthesized. These derivatives were covalently attached through the 5'-phosphoramide linkage to heptanucleotide pd(CCAAACA). Complementary complexes of the octanucleotide pd(TGTTTGGC) and above oligonucleotide conjugates were tested for their thermodynamic response. The Tm data and thermodynamic parameters for complex formation have demonstrated the ability of chromone (gamma-pyrone) and coumarin (alpha-pyrone) derivatives to stabilize strongly 7-mer/8-mer complementary complex, most likely through the stacking interaction of the pyran aromatic system with the neighboring nucleotide bases. The effect of chromone (or coumarin) derivatives on the stability of the oligonucleotide complexes (delta delta G at 37 degrees C ranged from -1.0 to -1.7 kcal/mol) was shown to be comparable to the effect of one nucleotide base pair and similar to the effect (delta delta G at 37 degrees C ranged from -1.5 to -2.0 kcal/mol) found for acridineoligonucleotide conjugates served in this study as a reference.
Laser therapy was assessed for effects on lipoperoxides and free radical catchers in blood lipids of patients with bronchial asthma (BA). When a group of 52 BA patients was compared to healthy donors by dienic conjugates, vitamin E and overall lipid-soluble antioxidants levels in the whole blood and plasma, these appeared higher in the asthmatics. Combination of laser therapy with conventional treatment returned these parameters close to normal.
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Lipid peroxidation and blood rheology were assessed in the course of treatment with antioxidant histochrome and placebo of 66 unstable angina pectoris (UAP) patients. Histochrome has a high antioxidant activity and effectively inhibits accumulation of lipoperoxides in plasma and red cells of UAP patients, promotes stabilization of blood cell function and structures, reduces red cell and platelet aggregation.
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Using one- and two-dimensional 1H NMR spectroscopy (400 MHz), a detailed study of the spatial structure of the covalent adduct, a product of the intracomplex alkylation of octanucleotide pd[TGTTTGGC] by the 4-[N-methyl-N-(2-chloroethyl)amino]benzyl-5'-phosphamide derivative of heptanucleotide pd[CCAAACA] in aqueous solution, was continued. The distances between closely spaced protons of oligonucleotides as well as between protons of the benzylamide fragment and protons of the nearest nucleotide units were determined by measurements of the nuclear Overhauser effect. Analysis of effective correlation times for some pairs of protons of the covalent adduct showed that the values of tau c for the benzylamide fragment and nucleotide units C-1 and C-8, which directly interact with it, coincide and are smaller than those for the internal nucleotide units, suggesting the increased rigidity of the structure in the vicinity of the modification region. Using the method of constrained molecular mechanics, a probable state of the covalent adduct in solution is proposed that is in the best agreement with the experimentally obtained set of interproton distances. Problems connected with calculating the distance between a pair of protons with coincident chemical shifts and any third proton are considered.
Thermal stability was studied and thermodynamic parameters of complex formation were calculated for pentanucleotide complexes [formula: see text] and corresponding complexes of pentanucleotide derivatives carrying at their 5'- or 3'-ends covalently bound residues of intercalating dyes: N-(2-hydroxyethyl)-phenazine (Phn) or 2-N-(3-aminopropionyl)-ethidium. Pentanucleotide derivatives were shown to form more stable complementary complexes. The best stabilizing effect was observed when the dye was oriented towards the long single-stranded fragment of tetradecanucleotide, melting temperature of the complexes being by 22.5 (Phn) and 31.2 degrees C (Etd) greater than that of unmodified complexes in the case of 5'-derivatives and by 21.6 (Phn) and 27.2 degrees C (Etd) for 3'-derivatives. Cooperativity constant of pentanucleotide derivatives in "tandem" complexes IV-VII was higher than that of unmodified pentanucleotide. For complex IV at 37 degrees C the constant values were 33 (unmodified), 35 (5'Phn), 57 (3'Phn), 190 (5'Etd), 100 (3'Etd). With n = 3 in complex VII cooperativity constants approached 1 in any case.