[EVALUATION OF THE MEDICAL AND ECONOMIC EFFICIENCY OF NON-INVASIVE PRENATAL TESTING IN MOSCOW].

AIM: to evaluate the medical and economic efficiency of prenatal diagnostics of fetal chromosomal abnormalities (CA) in pregnant women in Moscow using a non-invasive prenatal test (NIPT) as a second-line model. A comparative analysis of the medical and economic efficiency of standard prenatal screening and prenatal screening with NIPT in groups of pregnant women, registered in Moscow, with high and medium fetal CA risk was carried out. Analysis was based on the number of children born with CA and the costs of medical care (direct costs) and social payments (indirect costs), calculated for both scenarios. Following standard prenatal screening 111 children with CA would be born, following prenatal screening with NIPT - only 26. Including NIPT in prenatal diagnostics increases direct costs by 299.97 million rubles and reduces annual indirect costs from 61.19 to 28.95 million rubles. Starting from the 13th year of using NIPT the estimated effect of reducing indirect costs would exceed direct costs. NIPT in prenatal diagnostics can increase the detection of fetal CA and reduce indirect costs. Assessing the indirect costs in economic efficiency enhances the accuracy of the estimate.

[Clinical portrait of a patient with COVID-19. The experience of a multidisciplinary clinic].

AIM: Evaluation of the clinical characteristics in patients with COVID-19. MATERIALS AND METHODS: The article presents clinical and instrumental data of 1169 patients included in a single-center mixed study. Patients were tested for COVID-19 using polymerase chain reaction, computed tomography (CT), and antibody screening. Clinical history data were collected. RESULTS: In patients with confirmed COVID-19, lung damage and a positive test for antibodies were observed in 75.5 and 45.2% of cases, respectively. The most common symptoms of COVID-19 were: fever (73.2%), weakness, (72.7%) dry cough (62.8%) and shortness of breath (55.4%). Patients with CT-visualized lung lesions were more likely to have clinical symptoms and elevated levels of antibodies. Patients with chronic diseases of the endocrine system, circulatory system, and respiratory system had a more severe course of the disease (CT-14: 91.296.3%) than patients without chronic diseases (CT-14: 85,1%). CONCLUSION: We have compiled a clinical profile of patients with COVID-19 and highlighted the most significant clinical characteristics corresponding to a more severe course of the disease. Our data showed that patients with chronic diseases require a personalized approach and the development of specific criteria for the diagnosis and treatment of COVID-19.

Clostridium difficile in inflammatory bowel disease.

AIM: To study epidemiology and risk factors for Clostridium infection (CDI) associated with Clostridium difficile in patients with inflammatory bowel disease (IBD). MATERIALS AND METHODS: 1179 medical records were analyzed in a retrospective study of patients with IBD, of which 764 patients met the inclusion criteria. Patients were divided into 2 groups based on the presence of a preliminary diagnosis of CDI. Statistical analysis was carried out using Pearson Chi-square and two-sample t-test. RESULTS: The incidence of CDI in patients with IBD was 17.3%, with the same prevalence in patients with Crohn's disease (CD) (n=53/40.1%) and ulcerative colitis (UC) (n=79/59.9%). The mean age of occurrence of CDI in patients with IBD was 37.8±12.9, 84.8% of infections were community-acquired and only 4.5% occurred in medical institutions. Only 21.2% of all patients with CDI had a history of antibiotic use, and 24.2% had previously used steroids. Long-term immunosuppressive therapy in patients with IBD has an impact on the development of CDI: among patients with CDI 45.5% long-term received azathioprine/6-mercaptopurine, in patients without IBD - 17.7% (p<0.001). 18% of patients with CDI had control of the disease with salicylate therapy, while 62% of patients without CDI achieved remission by taking salicylates (p<0.05). CONCLUSION: The prevalence of CDI in UC and CD is comparable (p=0.16). The study shows that patients with IBD are more sensitive to the development of CDI at a young age, while not having such traditional risk factors as recent hospitalization or antibiotic use. Patients with IBD with CDI in history often noted the ineffectiveness of therapy with salicylates, often require the assignment of biological therapy. IBD patients with CDI have a lower average albumin, and a higher activity of the inflammatory process.

[Comparative Analisys of Efficacy of Countermeasure Provided by Different Modes of Locomotor Training in Space Flight.]

According to the results of the experiment performed on the ISS with participation of 15 Russian cosmonauts was fulfilled the comparative analysis of two models of preventive measures used by the Russian members of the long term space flight: the intense interval training in the aerobic-anaerobic zone power (recommended model) and the continuous low-intensity exercise in the aerobic zone energy power of the muscle activity. The interval trainings in the conditions of the space flight have provided the maintenance of the level of physical performance close to the preflight level; characterized by the maximum running speed, physiological value of work and lactate level after a standard load. The putative mechanisms of counteraction to adaptive remodeling of the propulsion system in zero gravity and enhanced understanding of the laws governing the interaction of the human body with the gravitational field of the Earth are described in the paper. The research results presented in the article show the high preventive efficacy of interval training compared with regular aerobic trainings, what is very important now in the time of searching of the means and methods of prevention of hypogravitation alterations during the interplanetary missions.

[Factorial structure of physical performance in children aged of 7-8 years].

The given research is devoted to the comprehensive investigation of physical working capability within the whole range of accessible loads in healthy schoolchildren aged of 7-8 years (n=159). During the working process there were identifiedfive important facts determining the structure ofpupils 'physical working capability in the researched aged group. They include common working capability, aerobic alactant working capability, anaerobic glycolytic working capability, aerobic power and aerobic volume. The pointed out facts except the fact of common working capability, are associated with the maximum, sub maximum, large and medium zones of relative capacity respectively. During the study there were found out the expressed differences between boys and girls according to the development level of aerobic and anaerobic components ofphysical working capability. Therewith the most substantial differences were observed concerning the variables characterizing the working capability in zones of large and medium power dealing predominantly with aerobic muscle activity power supply, and the least valuable ones - in accordance with working indices in the sub maximum power dealing with anaerobic glycolytic system. The received data can be applied in solving practical problems of hygienic rating and control ofphysical loads value of different relative power during the process of physical education as well as in prenosological diagnostics of children's health on the base of the evaluation of their organism's adaptative capabilities.

Topical axitinib suppresses angiogenesis pathways induced by pulsed dye laser.

BACKGROUND: The recurrence of port-wine stain (PWS) blood vessels by pulsed dye laser (PDL)-induced angiogenesis is a critical barrier that must be overcome to achieve a better therapeutic outcome. OBJECTIVES: To determine whether PDL-induced angiogenesis can be suppressed by topical axitinib. METHODS: The mRNA expression profiles of 86 angiogenic genes and phosphorylation levels of extracellular signal regulated kinases (ERKs), phosphorylated protein kinase B (AKT) and ribosomal protein S6 kinase (p70S6K) in rodent skin were examined with or without topical axitinib administration after PDL exposure. RESULTS: The PDL-induced increased transcriptional levels of angiogenic genes peaked at days 3-7 post-PDL exposure. Topical application of 0·5% axitinib effectively suppressed the PDL-induced increase in mRNA levels of the examined angiogenic genes and activation of AKT, P70S6K and ERK from days 1 to 7 post-PDL exposure. After topical administration, axitinib penetrated into rodent skin to an approximate depth of 929·5 µm. CONCLUSIONS: Topical application of 0·5% axitinib can systematically suppress the PDL-induced early stages of angiogenesis via inhibition of the AKT/mammalian target of rapamycin/p70S6K and Src homology 2 domain containing transforming protein-1/mitogen-activated protein kinase kinase/ERK pathway cascades.

[Proliferative and secretory activity of human umbilical vein endothelial cells cultured under varying degrees of hypoxia].

In this study we examined the impact of 3-day hypoxia of varying degrees on the viability, proliferative and secretory activity of endothelial cells in human umbilical vein (HUVEC). The gas mixture of the three components (%) was used: 1) 10 O2, 5 CO2, 85 Ar; 2) 5 O2, 5 CO2, 90 Ar and 3) 1 O2, 5 CO2, 94 Ar. The HUVEC, cultivated in CO2-incubator under conditions of atmospheric oxygen (21% O2) were the controls. Comprehensive assessment of the results after has shown that 3-day HUVEC cultivating in the presence of 1% O2 led to pathological activation of endotheliocytes: increased NO synthesis combined with the marked secretion of endothelin-1, IL-6, IL-8 and TNF-alpha, sVCAM-1, sE-cadherin and of sE-selectin, VEGF-A and bFGF, and slow proliferation. When HUVEC were cultivated at 10% O2 and 5% O2, the level of basal secretion of the substances listed above was the least against the background of increased proliferative activity. The results showing the changes in the secretory activity of endothelial cells when cultivated under the conditions of atmospheric oxygen levels have demonstrate HUVEC activation, because the secretion of NO, IL-6, IL-8 and von Willebrand factor after 3 days of cultivation in 21% 02 exceeded that in the case of 10 and 5% O2. Thus, a gaseous medium with reduced oxygen content of up to 5% provides more physiological conditions for HUVEC cultivation. The maximum proliferative activity of HUVEC with minimal basal secretion proved such a composition to be comfortable. Increasing the oxygen content to the atmospheric level leads to the activation of endotheliocytes with signs of endothelial dysfunction, and the critical reduction in oxygen to 1% causes the development of endothelial dysfunction and reduces the proliferative potential.

16(th) IHIW: analysis of HLA population data, with updated results for 1996 to 2012 workshop data (AHPD project report).

We present here the results of the Analysis of HLA Population Data (AHPD) project of the 16th International HLA and Immunogenetics Workshop (16IHIW) held in Liverpool in May-June 2012. Thanks to the collaboration of 25 laboratories from 18 different countries, HLA genotypic data for 59 new population samples (either well-defined populations or donor registry samples) were gathered and 55 were analysed statistically following HLA-NET recommendations. The new data included, among others, large sets of well-defined populations from north-east Europe and West Asia, as well as many donor registry data from European countries. The Gene[rate] computer tools were combined to create a Gene[rate] computer pipeline to automatically (i) estimate allele frequencies by an expectation-maximization algorithm accommodating ambiguities, (ii) estimate heterozygosity, (iii) test for Hardy-Weinberg equilibrium (HWE), (iv) test for selective neutrality, (v) generate frequency graphs and summary statistics for each sample at each locus and (vi) plot multidimensional scaling (MDS) analyses comparing the new samples with previous IHIW data. Intrapopulation analyses show that HWE is rarely rejected, while neutrality tests often indicate a significant excess of heterozygotes compared with neutral expectations. The comparison of the 16IHIW AHPD data with data collected during previous workshops (12th-15th) shows that geography is an excellent predictor of HLA genetic differentiations for HLA-A, -B and -DRB1 loci but not for HLA-DQ, whose patterns are probably more influenced by natural selection. In Europe, HLA genetic variation clearly follows a north to south-east axis despite a low level of differentiation between European, North African and West Asian populations. Pacific populations are genetically close to Austronesian-speaking South-East Asian and Taiwanese populations, in agreement with current theories on the peopling of Oceania. Thanks to this project, HLA genetic variation is more clearly defined worldwide and better interpreted in relation to human peopling history and HLA molecular evolution.

[Comparative efficacy of different regimens of locomotor training in long-term space flights by the data of biomechanical and electromyographic parametrs of walking].

Biomechanical and electromyographic characteristics of locomotion were investigated before and after space flight on the 3rd, 7th and 10th day after landing in 18 cosmonauts--crewmembers of long-term ISS space flights. It was shown that microgravity causes the development of significant changes in biomechanical and electromyographic characteristics of walking. Decrease of the angular displacement amplitude in leg joints, reduction of the length of the double step, increase of the electromyographic cost of locomotion were recorded after flight. It was also shown that interval locomotor physical training in long-term space flights in the regimen of alternation running and walking prevents physiological cost of locomotor movements increase after space flight and provides more effective maintenance of the neuromuscular system functions after flight. After flight smaller changes of biomechanical and electromyographic characteristics of walking were observed in cosmonauts who used locomotor training in interval regimen.

HLA gene and haplotype frequencies in Russians, Bashkirs and Tatars, living in the Chelyabinsk Region (Russian South Urals).

We have characterized the HLA-A, -B, -DRB1, -DQA1 and -DQB1 profiles of three major ethnic groups living in Chelyabinsk Region of Russian South Urals, viz., Russians (n = 207), Bashkirs (n = 146) and Tatars (n = 135). First field level typing was performed by PCR using sequence-specific primers. Estimates included carriage and gene frequencies, linkage disequilibrium and its significance and related values. Population comparisons were made between the allele family frequencies of the three populations and between these populations and 20 others using a dendrogram. Chelyabinsk Region Russians demonstrate all the features typical of a Caucasoid population, but also have some peculiarities. Together with Tatars, Russians have high frequencies of allele families and haplotypes characteristic of Finno-Ugric populations. This presupposes a Finno-Ugric impact on Russian and Tatar ethnogenesis. However, this was not apparent in Bashkirs, the first of the three populations to live in this territory, and implies admixture with populations of a Finno-Ugric origin with precursors of Russians and Tatars before they came to the South Urals. The Bashkirs appear close to Mongoloids in allele and haplotype distribution. However, Bashkirs cannot be labelled either as typical Mongoloids or as Caucasoids. Thus, Bashkirs possess some alleles and haplotypes frequent in Mongoloids, which supports the Turkic impact on Bashkir ethnogenesis, but also possess the AH 8.1 haplotype, which could evidence an ancient Caucasoid population that took part in their ethnic formation or of recent admixture with adjacent populations (Russians and Tatars). Bashkirs showed no features of populations with a substantial Finno-Ugric component, for example Chuvashes or Russian Saami. This disputes the commonly held belief of a Finno-Ugric origin for Bashkirs. Tatars appeared close to many European populations. However, they possessed some characteristics of Asiatic populations possibly reflecting a Mongoloid influence on Tatar ethnogenesis. Some aspects of HLA in Tatars appeared close to Chuvashes and Bulgarians, thus supporting the view that Tatars may be descendents of ancient Bulgars.

[Psychophysiological factors of readiness children of 6 years to education at school].

Research was spent according to principles of biomedical ethics. Healthy children of 6 years have taken part in him (n = 120). In the course of research the psychophysiological factors defining readiness of children of 6 years to education at school are identified: "selectivity of voluntary attention" (the factor I); "the general working capacity" (the factor II); "a physiological maturity" (the factor III); "sensorimotor coordination of voluntary movement" (the factor IV). Factors I, II, IV correspond with activity of three blocks of the brain allocated with A.R. Lurija within the limits of structurally functional model of work of a brain as a substratum of mental activity. The carried out research has revealed interrelation of some indicators of readiness for education at school with parametres of physical working capacity.

[Features of steroidogenesis in men with hypogonadism and type 2 diabetes].

BACKGROUND: Type 2 diabetes mellitus (DM2) in men is associated with a high incidence of hypogonadism. Testosterone is a steroid hormone and one of the final metabolites of steroidogenesis, which causes interest in assessing the content of key steroid hormones, their precursors and metabolites in hypogonadal and eugonadal men with T2DM. AIMS: Assessment of the features of steroidogenesis in men with hypogonadism in T2DM using tandem mass spectrometry. MATERIALS AND METHODS: A full-design, cross-sectional, screening, single-center, non-interventional study included men with T2DM, who were he was treated in Endocrinology Research Centre, Moscow. The study was conducted from October 2021 to January 2022. Medical history assessment, physical examination with determination of body mass index (BMI), measurement of key steroid hormones, their precursors and metabolites by isotope dilution liquid chromatography/tandem mass spectrometry, glycated hemoglobin (HbA1c) were performed. The groups were compared using the Mann-Whitney U-test for quantitative indicators and χ² with Yates' correction for qualitative ones. Correlation analysis was performed by the Spearman correlation method. When determining the criterion of statistical significance, the Bonferroni correction was applied. RESULTS: Patients with hypogonadism had statistically significantly more pronounced obesity compared with eugonadal men. In a comparative analysis of patients, depending on the presence of hypogonadism, there were statistically significantly lower levels of androgen precursors 17-hydroxypregnenolone and 17-hydroxyprogesterone in hypogonadal men. At the same time, a positive statistically significant correlation was found between total testosterone and 17-hydroxyprogesterone. In addition, 17-hydroxyprogesterone, although to a lesser extent, but positively correlated with other androgens - androstenedione (r=0,328; p<0,001) and dehydroepiandrosterone (r=0,183; p=0,004). >< 0,001) and dehydroepiandrosterone (r=0,183; p=0,004). CONCLUSIONS: In this investigation the prevalence of male hypogonadism in type 2 diabetes, determined by high-precision tandem mass spectrometry, was 69,5%. There was no effect of the disease on the mineralocorticoid and glucocorticoid links of adrenal steroidogenesis. Hypogonadism was associated with decreased levels of a number of testosterone precursors. The most significant of them was 17-hydroxyprogesterone, which can be considered as a marker of testicular steroidogenesis.

[Comparative impact analysis of risk factors on the course and outcomes of pregnancy with gestational diabetes mellitus].

BACKGROUND: The increasing prevalence of gestational diabetes mellitus (GDM), the high probability of unfavorable pregnancy outcomes for the mother and the fetus, as well as a number of long-term consequences in GDM are a serious medical and social problem and require the need for its prevention by correcting risk factors, timely diagnosis and effective treatment. AIM: Analysis of risk factors for the development of gestational diabetes mellitus (GDM), the relationship between GDM, the course and outcomes of pregnancy. MATERIALS AND METHODS: Retrospective analysis of 79 case histories of patients with confirmed GDM in the period from 2015 to 2017. RESULTS: In the structure of risk factors for mother and fetus, age over 30 years (73.1%), burdened heredity for type 2 diabetes mellitus (T2DM) (30.8%), mother's pre-pregnancy body mass index (BMI) (overweight / obesity (26.9%)) had the greatest impact. Among the complications of pregnancy, the most common was the caesarean section (47.4%). The incidence of other complications (macrosomia (9%), premature birth (7.7%), congenital malformations of the fetus (5.1%), preeclampsia (5.1%) was lower than the average frequency of these complications in GDM, described in the literature. Nevertheless, it is 1.5-2 times higher than the average population indicators. In the course of statistical analysis of the data it was revealed, that the higher the mother's pre-pregnancy BMI, the lower the Apgar score for the first minute in the newborn. CONCLUSION: Women with GDM require intensive monitoring of the course of pregnancy and timely hospitalization for planned delivery, and the provision of competent obstetric benefits.

HLA gene and haplotype frequencies in a Nagaybaks population from the Chelyabinsk Region (Russian South Urals).

A total of 112 Nagaybaks, a Turkic ethnoconfessional group living mainly in the Nagaybak district of the Chelyabinsk Region of Russian South Urals, were genotyped for HLA-A, -B, -DRB1, -DQA1 and -DQB1 loci using PCR-SSP (low-resolution) and HLA-A29 (high-resolution). All loci were in Hardy-Weinberg equilibrium (all p values >0.1 thus showing no locus-level deviations. The genotype data are available in the Allele Frequencies Net Database under the population name ''Russia, South Ural, Chelyabinsk Region, Nagaybaks" and the identifier AFND0003397.

Functional consequences of mutations in the transmembrane domain and the carboxy-terminus of the murine AE1 anion exchanger.

We have characterized mouse AE1-mediated 36Cl- influx and surface AE1 polypeptide expression in Xenopus oocytes injected with cRNA encoding two classes of loss-of-function mutants. The first arose spontaneously. Chimeric mutants constructed with a functional AE1 cDNA localized the site of spontaneous mutation to the transmembrane domain, and DNA sequencing revealed two missense mutations encoding the double-mutant polypeptide V728F/M7301. Each mutation individually produced only partial loss of AE1 transport activity, and coexpression of the individual mutants did not restore full activity. The functional changes produced by the mutations correlated with reduced fractional accumulation of polypeptides at the oocyte surface. The V728F/M7301 polypeptide expressed in mammalian cells displayed complete endoH resistance and rapid degradation. We also examined the effect on AE1 function of engineered removal of its hydrophilic carboxy-terminus. Both delta(c)890 and the internal deletion delta(c)890-917 were functionally inactive in Xenopus oocytes. Lack of transport activity correlated with lack of detectable polypeptide accumulation at the oocyte surface. Coexpression with wt AE1 of some, but not all, of these AE1 mutants partially suppressed wt AE1-mediated 36Cl- uptake. In contrast, coexpression with wt AE1 of soluble N-terminal AE1 fragments was not inhibitory.

Regulation of AE2-mediated Cl- transport by intracellular or by extracellular pH requires highly conserved amino acid residues of the AE2 NH2-terminal cytoplasmic domain.

We reported recently that regulation by intracellular pH (pH(i)) of the murine Cl-/HCO(3)(-) exchanger AE2 requires amino acid residues 310-347 of the polypeptide's NH(2)-terminal cytoplasmic domain. We have now identified individual amino acid residues within this region whose integrity is required for regulation of AE2 by pH. 36Cl- efflux from AE2-expressing Xenopus oocytes was monitored during variation of extracellular pH (pH(o)) with unclamped or clamped pH(i), or during variation of pH(i) at constant pH(o). Wild-type AE2-mediated 36Cl- efflux was profoundly inhibited by acid pH(o), with a value of pH(o50) = 6.87 +/- 0.05, and was stimulated up to 10-fold by the intracellular alkalinization produced by bath removal of the preequilibrated weak acid, butyrate. Systematic hexa-alanine [(A)6]bloc substitutions between aa 312-347 identified the greatest acid shift in pH(o(50)) value, approximately 0.8 pH units in the mutant (A)6 342-347, but only a modest acid-shift in the mutant (A)6 336-341. Two of the six (A)6 mutants retained normal pH(i) sensitivity of 36Cl- efflux, whereas the (A)6 mutants 318-323, 336-341, and 342-347 were not stimulated by intracellular alkalinization. We further evaluated the highly conserved region between aa 336-347 by alanine scan and other mutagenesis of single residues. Significant changes in AE2 sensitivity to pH(o) and to pH(i) were found independently and in concert. The E346A mutation acid-shifted the pH(o(0) value to the same extent whether pH(i) was unclamped or held constant during variation of pH(o). Alanine substitution of the corresponding glutamate residues in the cytoplasmic domains of related AE anion exchanger polypeptides confirmed the general importance of these residues in regulation of anion exchange by pH. Conserved, individual amino acid residues of the AE2 cytoplasmic domain contribute to independent regulation of anion exchange activity by pH(o) as well as pH(i).

Electrogenic sulfate/chloride exchange in Xenopus oocytes mediated by murine AE1 E699Q.

Functional evaluation of chemically modified human erythrocytes has led to the proposal that amino acid residue E681 of the band 3 anion exchanger AE1 lies on the anion translocation pathway and is a proton carrier required for H+/SO4(2-) cotransport. We have tested in Xenopus oocytes the functional consequences of mutations in the corresponding residue E699 of mouse AE1. Most mutations tested abolished AE1-mediated Cl- influx and efflux. Only the E699Q mutation increased stilbene disulfonate-sensitive efflux and influx of SO4(2-). E699Q-mediated Cl- influx was activated by elevation of intracellular SO4(2-), but E699Q-mediated Cl- efflux was undetectable. The DNDS (4,4'-dinitrostilbene-2,2'-disulfonic acid) sensitivity of E699Q-mediated SO4(2-) efflux was indistinguishable from that of wt AE1-mediated Cl- efflux. The extracellular anion selectivity of E699Q-mediated SO4(2-) efflux was similar to that of wt AE1-mediated Cl- efflux. The stoichiometry of E699Q-mediated exchange of extracellular Cl- with intracellular SO4(2-) was 1:1. Whereas SO4(2-) injection into oocytes expressing wt AE1 produced little change in membrane potential or resistance, injection of SO4(2-), but not of Cl- or gluconate, into oocytes expression E699Q depolarized the membrane by 17 mV and decreased membrane resistance by 66%. Replacement of bath Cl- with isethionate caused a 28-mV hyperpolarization in SO4(2-)-loaded oocytes expressing E699Q, but had no effect on oocytes expressing wt AE1. Extracellular Cl(-)-dependent depolarization of SO4(2-)-preloaded oocytes was blocked by DNDS. AE1 E699Q-mediated inward current measured in the presence of extracellular Cl- was of magnitude sufficient to account for measured 35SO4(2-) efflux. Thus, AE1 E699Q-mediated SO4(2-)/Cl- exchange operated largely, if not exclusively, as an electrogenic, asymmetric, 1:1 anion exchange. The data confirm the proposal that E699 resides on or contributes to the integrity of the anion translocation pathway of AE1. A single amino acid change in the sequence of AE1 converted electroneutral to electrogenic anion exchange without alteration of SO4(2-)/Cl- exchange stoichiometry.

Calmodulin-independent bovine brain adenylate cyclase. Amino acid sequence and nucleotide sequence of the corresponding cDNA.

An individual catalytic component of calmodulin-independent adenylate cyclase has been isolated from bovine brain cortex. Affinity chromatography on an immunosorbent was used. The amino acid sequence of adenylate cyclase as well as the corresponding nucleotide sequence of the cDNA has been determined. cDNA of adenylate cyclase encodes a protein consisting of 834 amino acid residues and the signal peptide (19 amino acid residues). A series of adenylate cyclase isoforms has been found. A homology between adenylate cyclases from bovine brain, E. coli and Bordetella pertussis has been revealed.

Regulation of Na+-independent Cl-/HCO3- exchangers by pH.

Among human bicarbonate transporters, two major gene families encode Na-independent Cl(-)/HCO(3)(-) exchangers: the SLC4 anion exchanger (AE) family, and the SLC26 "sulfate permease" anion transporter family. The SLC4 AE family contains at least three genes, and comprises a subfamily within the larger and phylogenetically more ancient bicarbonate transporter superfamily that includes the Na bicarbonate cotransporters (NBC) and the Na-driven Cl/base exchangers. Mutations in the human AE1 gene cause autosomal dominant spherocytic anemia and distal renal tubular acidosis of both dominant and recessive forms. Anemia is also associated with AE1 mutations in mouse, cow, and zebrafish. Naturally occurring mutations in the human AE2 and AE3 genes have not been detected. The SLC26 family in humans consists of at least 10 members, and includes anion exchangers which exchange chloride for bicarbonate, hydroxyl, sulfate, formate, iodide, and/or oxalate. Mutations in three of these genes cause hereditary disease, including chondrodysplasia (SLC26A2, DTD), diarrhea (A3, down-regulated in adenoma/chloride-losing diarrhea protein: DRA/CLD), and goiter/deafness syndrome (A4, pendrin). Little is known about the acute regulation of these modulators of intracellular and compartmental pH and volume.

[Spontaneous closure of the interventricular septal defects in children]. / O spontannom zakrytii defekta mezhzheludochkovoi peregorodki u detei

A total of 214 patients with a defect of the interventricular septum have been examined starting from the first days of their life and to the age of 7 years. In 50 of them the defect closed spontaneously (23.4 per cent). Twenty of these patients had a complicated course of the defect (circulatory insufficiency, colds and pneumonia). The spontaneous closure of the interventricular septum defect occurred most frequently at the age of from 1 to 4 years (86 per cent).