The Clinical Evolution of Diffuse Myocardial Fibrosis in Patients With Arterial Hypertension and Heart Failure With Mildly Reduced Ejection Fraction Treated by Olmesartan or Sacubitril / Valsartan.

Aim      A 12-month evaluation of the potentialities of the angiotensin II receptor inhibitor olmesartan (Olme) and the angiotensin receptor and neprilysin inhibitor (ARNI) sacubitril/valsartan in patients with arterial hypertension (AH) and dyslipidemia in the dynamics of the following indicators of chronic heart failure (CHF): N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), LV global longitudinal strain (LV GLS) in diffuse myocardial fibrosis (MF) previously diagnosed by magnetic resonance imaging (MRI).Material and methods  Olmesartan medoxomil (n=56) and sacubitril/valsartan (n=63) were used for 12 months in patients with hypertension, dyslipidemia and NYHA functional class II-III CHF with mid-range LVEF (CHFmrEF). MF was diagnosed by the following MRI criteria: late gadolinium enhancement and an increased proportion of extracellular matrix (33% or more). The frequency of persisting late gadolinium enhancement and the increased proportion of extracellular matrix (33% or more) was evaluated at 12 months; changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), NT-proBNP, and LV GLS were evaluated after 3, 6, and 12 months of follow-up.Results Baseline parameters did not differ between groups. The late gadolinium enhancement and increased proportion of extracellular matrix were present at baseline in all patients of both groups (100%; p=1.0). Already at 3 months, statistically significant decreases in SBP and DBP were observed in both groups. In addition, the LV GLS monitoring showed LV GLS significantly increased in both groups after 3 months and continued changing after 6 and 12 months. The NT-proBNP concentration significantly decreased in both groups already after 3 months and continued to decrease after 6 and 12 months. At 6 and 12 months, sacubitril/valsartan was superior to olmesartan in reducing SBP and NT-proBNP and in restoring LV GLS. At 12 months, the incidence of persisting, abnormal late gadolinium enhancement and increased proportion of extracellular matrix was significantly less in the ARNI group.Conclusion      Olmesartan was demonstrated effective in the multi-modality therapy of CHFmrEF and MF in patients with AH and dyslipidemia. ARNI was superior to olmesartan in this regard, but further research of this issue is required.

[Ability to Overcome the Thrombocyte Resistance to Acetylsalicylic Acid in Patients With Coronary Artery Disease After Myocardial Revascularization With Coronary Stenting].

Resistance to acetylsalicylic acid (ASA) in patients with coronary artery disease is a poor predictor for the development of atherothrombotic complications. In 277 patients with coronary artery disease suffered uncomplicated coronary angioplasty with stent implantation, we was estimated arachidon-induced platelet aggregation during treatment with acetylsalicylic acid by bedside VerifyNow Assay test at 28-90 days after the intervention. It was found that 18.9% of the 144 patients receiving a combination of ASA 75 mg with 15.2 mg of magnesium hydroxide had true (laboratory) resistance to ASA. At the same time on the original enteric coated ASA 100 mg, we can found only 0.8% resistance to ASA among 129 patients. We made switch from combination of ASA 75 mg with 15.2 mg of magnesium hydroxide to original enteric coated ASA 100 mg and repeat VerifyNow Assay test at 2-4 days and found lost of resistance in 92% of 28 patients. Thus, resistance to the ASA is not constant, it depends on the form and the applied dose of ASA, and eliminating more than 92% when ASA changes from ineffective to effective form.

[The analysis of structure of insulin-dependent regulatory contours of mature adipocyte].

Insulin is the important regulator of adipose cell metabolism and activates the branched out network of the signaling pathways supervising glucose transport, glycogen synthesis, lipogenesis stimulation, lipolysis inhibition and adipokine secretion. The purpose of our work is the analysis of structure of regulatory contours providing the response of mammalian adipocytes to insulin. With use of computer technology GeneNet adipocyte regulatory-effector network has been reconstructed. The network generalizes experimental data concerning the main insulin-dependent signaling pathways and their targets in a context insulin-sensitive metabolic processes and transcription events. Analysis of the network revealed positive and negative regulatory contours including MAP kinase-, Cbl/TC10- and P13K-dependent signaling pathways. Regulatory contours functioning with participation of transcription factors SREBP-1c, PPARgamma/RXRalpha, C/EBPalpha, FOXO1 are defined also. The major effectors of regulatory contours are glucose carrier GLUT4, and kinase mTOR.

[Real-time polymerase chain reaction and its potential clinical application].

The review introduces real-time polymerase technique, a modern high-tech method, to the medical community. Physico-chemical principles of the method, its main stages, and variants of techniques applying fluorescent reporter platforms are considered. Equations used for quantitative estimation, methods of data processing are given; absolute and relative quantification of specific targets is considered. The special part of the review is dedicated to clinical application of the method by the example of infectious and oncological diseases.

[Use of antagonistic Bacillus subtilis bacteria for treatment of nosocomial urinary tract infections].

Effect of Bactisporin--a probiotic, containing spores of aerobic Bacillus subtilis 3H bacterium--for complex treatment of patients with nosocomial urinary tract infections was studied. 68 Cultures of different species of conditionally pathogenic bacteria were isolated from urine of the patients. Susceptibility of the isolated cultures to antibiotics before and after application of B. subtilis 3H metabolites was determined. The metabolites were accumulated on potato-glucose agar (PGA) while bacterium was cultivated on kapron membranes placed on surface of the medium. Influence of obtained metabolites on isolated strains was assessed by cultivation of each strain in metabolites-rich PGA during 24 h. Metabolites of B. subtilis led to decrease in resistance of isolated uropathogenic microflora to antibiotics. Use of Bactisporin in complex treatment of nosocomial urinary tract infections resulted in accelerated elimination of causative microorganism.

[Deletional polymorphism of the 11th intron of the human c-fms gene: allele frequency in certain Russian populations and possible functional significance]. / Deletsionnyi polimorfizm 11-go introna gena c-fms cheloveka: chastoty allelei v nekotorykh populiatsiiakh Rossii i vozmozhnaia funktsional'naia znachimost'.

Analysis of deletion polymorphism of human c-fms gene intron 11 (approximately 425-bp deletion) is of particular interest because of the increased proportion of the deletion heterozygotes among the infants born from the parents, one of which lacks the deletion allele, and the other is heterozygous for the deletion. In this study, allele and haplotype frequencies of the polymorphism examined were assessed in a number of Caucasoid and Mongoloid populations of Russia. In all populations tested, relatively high prevalence of the deletion-bearing allele, ranging from 9.45% in ethnic Germans to 20.75% in Altaians, was detected. Russians and Kazakhs were characterized by intermediate frequencies of the rare allele, constituting in these populations 12.89 and 14.93%, respectively. Hardy-Weinberg expectations were met in all populations examined, pointing to a stable level of polymorphism at the c-fms intron 11. It was established by the context analysis of DNA of the deleted fragment along with the flanking sequences that this region contained a number of transcription factor motifs (Ets, SRF, and Myc), potentially capable of the regulation of the M-CFF-dependant c-fms transcription. The deletion breakpoint was localized within the CArG motif, which, together with the neighboring ets motif, form the potential CArG/ets composite element. It was suggested that allele lacking the fragment of intron 11 could be restricted in its ability to modulate the level of the c-fms transcription in response to the action of M-CSF. The data of molecular epidemiological survey serve as the indirect evidence favoring the suggestion on the possible functional value of this gene fragment. It was demonstrated that in the samples of acute bronchitis and trichomoniasis patients allelic and genotype frequencies were statistically significantly different from those in the population sample. In case of trichmoniasis, the frequency of rare allele was 2.4 times lower, and in case of acute bronchitis it was 2.1 times higher than in the control sample.

[Detection of two polymorphic sites in the human c-fms gene: allele frequency and genotype in some populations of Russia]. / Obnaruzhenie dvukh polimorfnykh saitov v gene c-fms cheoveka: chastoty allelei i genotipov v nekotorykh populiatsiiakh Rossii.

Two polymorphic sites were found in the human c-fms gene: one (G-->A) was in position 34,047 in the last intron, and the other (dinucleotide TC-->CA) was in positions 34,293 and 34,294 in the 3'-untranslated gene region, 34 bp downstream of the translation stop codon. The polymorphic dinucleotide appeared to be immediately upstream of an octamer showing 100% homology to cis element -CAAACTTC-, which is responsible for controlled instability of mRNAs of several genes. Based on these data, functional significance was assumed for this polymorphism of the c-fms gene. Allele frequencies were established for several populations. The mutant allele of the polymorphism located in the intron were detected only in one family of ethnic Germans from the Altaiskii krai. Polymorphism of the second site, which is in the 3'-untranslated region of the c-fms gene, was observed in all Caucasoid and Mongoloid populations examined. Frequency of the rare allele varied from 19.7-25% in Arctic Mongoloids to 31-42.6% in Central Asian Mongoloids and was similar in two Caucasoid populations (22.6% in ethnic Russians and 26.5% in ethnic Germans). The wide distribution of the mutant allele in human populations of the two races was considered indicative of an adaptive role of the polymorphism in providing a certain level of the gene product, a receptor, in certain cell processes.

[Physicians and the population on the reforming of public health (based on sociological research data)]. / Vrachi i naselenie o reformirovanii zhdravookhraneniia (po dannym sotsiologicheskogo issledovaniia).

A sociological analysis of the opinions of physicians and population on public health reforms was carried out during the period of active introduction of obligatory medical insurance in Russia, that is, in July-August 1994 and 1995. A total of 4000 questionnaires distributed among the population and 2500 among physicians were analyzed using the random cluster and typological proportional sampling. The paper presents statistical data disclosing the opinion of the population and physicians on the process of introducing obligatory medical insurance as the priority improvement in the activity of outpatient health centers and on other reforms in public health. Analysis of public opinion demonstrated the difficulties of the present period and the reserves in improving the reformation of public health which may be used to ensure guaranteed volume of medical care rendered to the population.

[The safety, reactogenicity and antigenic activity of a Pseudomonas aeruginosa anatoxin studied in volunteers]. / Izuchenie bezopasnosti, reaktogennosti i antigennoi aktivnosti anatoksina Pseudomonas aeruginosa na dobrovol'tsakh.

The safety, reactogenicity and immunogenic activity of P. aeruginosa toxoid were studied in 46 volunteer donors. Systemic reactions to the injection of the preparation were absent in all vaccinees, in 2 subjects (4.3%) insignificant reactions at the site of injection in the form of hyperemia, sized 13-14 mm and disappearing within 48 hours, were registered. The preparation was found stimulate humoral immunity, which was manifested by an increase in the number of B-rosette-forming lymphocytes and the level of antitoxic IgG in the blood of the vaccinees. Besides, immune sera obtained from the blood of the volunteers were found to possess protective properties.

[The optimization of the batch cultivation process for Pseudomonas aeruginosa to produce exotoxin A]. / Optimizatsiia periodicheskogo protsessa kul'tivirovaniia Pseudomonas aeruginosa s tsel'iu polucheniia ékzotoksina A.

The experimental study of conditions for the optimization of the batch cultivation of P. aeruginosa has been made. As revealed in this study the aim of this cultivation can be achieved by using exponentially growing culture in a dose of 1.10(9) cells/ml as seed material and by ensuring the conditions of rational air supply during the main cultivation process.