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Biomedical subjects

A S Ivanov

Publications and source records attributed to A S Ivanov.

At least 19 recordsLinked to original sources

[Valve-preserving reconstructive surgical procedures on pulmonary artery root in Fallot's tetralogy].

Original surgical method of dilated valvuloplasty is described. In moderate isolated hypoplasia of the fibrous ring of the pulmonary artery this method permits one to perform organ-preserving reconstruction of this zone without transannular plastic operation. Schemes of the surgery, experimental data and clinical experience based on surgical treatment of 31 patients with Fallot's tetrad in combination with hypoplasia of the fibrous ring of the pulmonary artery are presented. Short- and long-term results of the defect correction are reported.

Adolescent↗

[Endovascular balloon valvuloplasty of pulmonary artery valvular stenosis].

Summarized experience of balloon valvuloplasty in isolated stenosis of pulmonary artery valve is analyzed. This procedure was performed in Russian Research Center of Surgery in 53 patients from 1980 to 2006. The technique of balloon valvuloplasty is described; short- and long-term results are analyzed. Complications and unsatisfactory results of this surgery are outlined.

Adolescent↗

[Short- and long-term results of balloon dilatation of aorta coarctation].

Balloon dilatation is an alternative method of aorta coarctation (AC) treatment, and it may be effective in 80 - 90% cases with appropriate indications. Arterial hypertension is one of the symptoms of AC and frequent complication of short- and long-term postoperative period. Surgical correction does not guarantee regress of pathological symptoms in all the cases, and method of surgery does not influence the rate of postoperative arterial hypertension. The study reviews CA balloon dilatation experience and analyses cases of late arterial hypertension rate in long-term period after balloon dilatation procedure.

Adolescent↗

[Methods of experimental validation of potential target proteins for creation of new drugs].

Review is devoted to the description of the main existing and developing technologies for experimental validation of potential targets predicted in silico by comparative genomics and bioinformatics methods. Since this problem has not been solved yet, the description of a wide set of methods, suitable for the validation of potential targets, is given. The following questions have been considered: (1) applications of proteomic technologies (control of potential targets expression and their variability, analysis of protein-protein interactions); (2) use of genomics technologies in experimental validation of targets (inactivation of the target genes, suppression of transcription, inactivation of the target mRNA, suppression of translation); (3) methods of direct inactivation of target proteins (monoclonal antibodies, light-inactivation, one-chain antibodies, intrabodies, aptamers); (4) high-throughput technologies; (5) targets validations in vivo.

Animals↗

[Anomalous origin of left coronary artery from pulmonary trunk: symptoms, diagnosis and surgical treatment].

Anomalous origin of left coronary artery from pulmonary artery is a rare congenital pathology causing death of most patients because of various arrhythmia and heart failure. The authors present 4 cases of this anomaly with description of clinical course, diagnosis and surgical procedures. The first patient was operated upon in 12 years after mitral valve replacement. Ligation of anterior interventricular and circumflex arteries at their origin in this patient was combined with anastomosis between mammary and anterior interventricular coronary arteries. Reimplantation of the left coronary artery into the aortic root was used in other 3 patients with good immediate postoperative effect. Restoration of left ventricular pump function occurred in all 3 patients.

Child↗

[Double disposition of the major vessels from the right ventricle of the Fallot tetralogy type].

Forty-six patients with double disposition of the major vessels from the right ventricle in combination with stenosis of the pulmonary artery, in sub-aortal and bi-committed defects of the interventricular septum have undergone biventricular intraventricular correction. The most specific and accurate anatomic characteristics were: 1) position of the major vessels (particularly side-to-side); 2) location of two and a part of the third aortal sinuses above the right ventricle; 3) bilateral cone; 4) absence of aorto-mitral contact; 5) location of valves of aorta and pulmonary artery on the same level. One (2,2%) patient died during surgery due to progressed cardiac insufficiency. One (2,5%) patient died 2 years after radical correction of the defect due to progressive dysfunction of the right ventricle.

Adolescent↗

Nonselective inhibition of monoamine oxidases A and B by activators of soluble guanylate cyclase.

Several activators of soluble guanylate cyclase were investigated as potential inhibitors of rat liver mitochondrial monoamine oxidases (MAO) A and B. They all fitted into the previously designed "molds" of substrate-inhibitor binding sites of these enzymes. However, only two of them, NO donors (7-nitro-benzotetrazine-1,3-dioxide (7-NBTDO) and benzodifuroxan), caused nonselective inhibition of MAO A and MAO B with IC(50) values of 1.3-1.6 and 6.8-6.3 microM, respectively. The inhibitory effect on both MAO A and MAO B was reduced by mitochondria wash suggesting reversible mode of the enzyme inhibition. There was no correlation between potency of MAO inhibition and activation of human platelet soluble guanylate cyclase. The NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) had no effect on the manifestation of MAO inhibition by benzodifuroxan and 7-NBTDO; however, at 50 microM concentration carboxy-PTIO caused potent inhibition of MAO A with minor effect on MAO B activity. The data suggest that nonselective inhibition of MAO A and MAO B by benzodifuroxan and 7-NBTDO can be attributed to the properties of the chemical structures of these compounds. The results of the present study demonstrate a real possibility for the development of a new generation of effective reversible nonselective MAO inhibitors exhibiting equal inhibitory activity with respect to both MAO A and MAO B.

Animals↗

Strategy of computer-aided drug design.

Modern strategies of computer-aided drug design (CADD) are reviewed. The task of CADD in the pipeline of drug discovery is accelerating of finding the new lead compounds and their structure optimization for the following pharmacological tests. The main directions in CADD are based on the availability of the experimentally determined three-dimensional structure of the target macromolecule. If spatial structure is known the methods of structure-based drug design are used. In the opposite case the indirect methods of CADD based on the structures of known ligands (ligand-based drug design) are used. The interrelationship between the main directions of CADD is reviewed. The main CADD approaches of molecule de novo design and database mining are described. They include methods of molecular docking, de novo design, design of pharmacophore and quantity structure-activity relationship models. New ways and perspectives of CADD are discussed.

Computational Biology↗

Modelling of three-dimensional structures of cytochromes P450 11B1 and 11B2.

The final steps of the biosynthesis of glucocorticoids and mineralocorticoids in the adrenal cortex require the action of two different cytochromes P450--CYP11B1 and CYP11B2. Homology modelling of the three-dimensional structures of these cytochromes was performed based on crystallographic coordinates of two bacterial P450s, CYP102 (P450BM-3) and CYP108 (P450terp). Principal attention was given to the modelling of the active sites and a comparison of the active site structures of CYP11B1 and CYP11B2 was performed. It can be demonstrated that key residue contacts within the active site appear to depend on the orientation of the heme. The obtained 3D structures of CYP11B1 and CYP11B2 were used for investigation of structure-function relationships of these enzymes. Previously obtained results on naturally occurring mutants and on mutants obtained by site-directed mutagenesis are discussed.

Amino Acid Sequence↗

An approach for visualization of the active site of enzymes with unknown three-dimensional structures.

A new approach for virtual characterization of the active site structure of enzymes with unknown three-dimensional (3D) structure has been proposed. It includes analysis of data on enzyme interaction with reversible competitive inhibitors, their 3D structures and moulding of the substrate-binding region. The superposition of ligands in biologically active conformations allows to determine the shape and dimension of the active site cavity accommodating these compounds. Monoamine oxidase A (MAO-A), a "typical" enzyme with unknown spatial organisation, was used to test this method. The correctness of such approach was validated by the analysis of HIV protease interaction with its inhibitors using 3D structures of their complexes. Mould of the substrate/inhibitor binding site can be used for the visualization of this binding site and for searching new ligands in molecular databases.

Databases, Factual↗

[Clinical, diagnostic and therapeutic features of tricuspid infectious endocarditis].

From 1987 to 1998, examination and treatment were conducted of 12 patients with infectious endocarditis of the tricuspid valve (TIE). 11 of them were operated. TIE was clinically characterized by lesser circulation thromboembolism and marked right ventricular failure. TIE was successfully diagnosed by echo-CG (diagnostic sensitivity 83.3%). Serious disturbances of cellular immunity demanded immunocorrection. Indications for surgical treatment are listed.

Adolescent↗

Influence of transketolase substrates on its conformation.

Dynamics stimulation of the holotransketolase molecule revealed that the enzyme's conformation in crystal was different from that in solution. It was shown also that dissolved holotransketolase can bind aldose (the acceptor substrate) even in the absence of ketose (the donor substrate). The holotransketolase conformation did not change upon aldose binding unlike in the case of ketose binding/cleavage. Therefore the conformation of a catalytic complex of holotransketolase with an intermediate-i.e., a glycolaldehyde residue formed upon binding and subsequent cleavage of ketose-differed, at least in solution, from the conformation of both the free and aldose-complexed holotransketolase. Some structural peculiarities of the holotransketolase with the intermediate were established by means of molecular dynamics stimulation.

Acetaldehyde↗

[Enalapril treatment of residual pulmonary hypertension in patients operated rheumatic mitral valve defects].

A pilot trial of efficiency of enalapril maleate in the treatment of residual pulmonary hypertension was made in 22 patients operated for rheumatic mitral valve defects. Degree I, II and III of pulmonary hypertension was registered in 5, 13 and 4 patients, respectively. Thus, the patients had NYHA functional classes III and IV (22.7 and 77.3%, respectively. Enalapril given for 6 months in a mean daily dose 12.3 +/- 1.57 mg/m2 (5-30 mg a day) normalized pressure in the pulmonary artery in 18.2% of patients. 50% of patients showed hypertension degree I, only one female retained hypertension degree III. To the end of the treatment the functional classes were the following: II--in 68.2%, III--in 27.3% and IV--in 4.5%.

Adult↗

[Program of examination for patients with isolated mitral valve defects to evaluate the degree of pulmonary hypertension].

98 patients with isolated rheumatic mitral valve defects of the heart entered the study. Their central hemodynamics was studied intraoperatively before surgical correction of the defect. The results were compared to those provided by conventional noninvasive methods: chest x-ray, ECG, echo-CG, external respiration function test. Correlation analysis using computer intellect PolyAnalyst v.1.01R helped to design a program and practical nomogram which can quantitatively determine the degree of pulmonary hypertension on the basis of digital values of Rv1 wave amplitude (ECG) and right ventricular cavity size (echoCG).

Adult↗

[Course of pulmonary hypertension in patients operated for rheumatic mitral heart disease].

AIM: To study changes in pulmonary hypertension in patients with isolated mitral valvular defects of rheumatic etiology after surgical correction and in the early postoperative period. MATERIALS AND METHODS: Central hemodynamics in heart chamber probing before operation and intraoperatively were measured in 98 patients with rheumatic mitral defects (41 males, 57 females, mean age 39.5 +/- 8.74). Manometry before and after the defect correction, intraoperative catheterization (cath. Swan-Ganz) for hemodynamics 24-h follow-up were made. RESULTS: After valvular defect correction 90(91%) patients had residual pulmonary hypertension, stage II-III in 41%. CONCLUSION: Patients operated for rheumatic heart disease complicated by pulmonary hypertension often suffer from residual pulmonary hypertension. This requires pharmacological correction.

Adult↗

[The possibilities for preventing adhesive disease after appendectomy].

The authors have developed a method for influencing the altered peritoneum in the area of the inflammation focus by insufflation of medical aerosol at the postoperative period for quicker reestablishment of integrity and physiological function of its mesothelium and fibrinolytic activity which allows the probability of forming commissures in patients after appendectomy to be reduced. Long-term follow-up (up to 3 years) of 61 patients operated upon by the proposed method showed that in 59 of then the results were excellent and good.

Acute Disease↗

Modeling of substrate-binding region of the active site of monoamine oxidase A.

The mold of the substrate-binding region of the active site of monoamine oxidase A (MAO A) was designed using data of the enzyme interaction with reversible competitive inhibitors and the analysis of their three-dimensional structures. The superposition of ligands in biologically active conformations allowed determination of the shape and dimension of the active site cavity accommodating these compounds. The correctness of this approach was validated by the analysis of HIV protease interaction with its inhibitors using three-dimensional structures of HIV protease-inhibitor complexes. The mold of the substrate/inhibitor-binding site can be used for searching for new ligands in molecular databases and the development of a new generation of MAO inhibitors using lead structures that have not been employed for this purpose yet.

Binding Sites↗