Impact of Experimental Tuberculosis on Fertility of Female BALB/c Mice.

The study revealed no effects of pregnancy and childbirth on the course of tuberculosis in female BALB/c mice after aerosol infection with Mycobacterium tuberculosis. However, we demonstrated a negative effect of tuberculosis infection on the fertility of infected females, which manifested in a longer period from mating to pregnancy and in a smaller litter size. Impaired reproductive function in response to the effect of the systemic infectious process was accompanied by the development of immunosuppression confirmed by an immunological test (delayed-type hypersensitivity to tuberculin) and the formation of genital tract dysbiosis during pregnancy and postpartum period.

Attenuated Strain of Mycobacterium tuberculosis BN: Characteristics.

We evaluated the vaccine properties of a novel attenuated strain of M. tuberculosis BN (Mtb BN) and its impact on the gut microbiota in inbred female mice in comparison with a virulent strain Mtb H37Rv and a vaccine strain BCG. The Mtb BN strain demonstrated the highest anti-tuberculosis vaccine effect in I/St mice highly susceptible to tuberculosis infection and the same effect as BCG in mice of the recombinant strain B6.I-100 and in ß2 microglobulin gene knockout mice. No adverse effects of the new Mtb BN strain on the gut microbiota of BALB/c mice were revealed. The virulent strain Mtb H37Rv and the vaccine strain BCG decreased the main indicators of normocenosis (Bifidobacterium spp., Bifidobacterium animalis subsp. lactis, Akkermansia, and Erysipelotrichaceae) and led to disappearance of Clostridium perfingens, E. coli, Pseudomonas spp., which contributed to reduction of species diversity and the development of dysbiosis.

Changes in Microbiota and Development of Nonspecific Inflammation of Genitals in Female C57Bl/6 Mice after Aerosol Infection with Mycobacterium tuberculosis.

Infectious process even at the initial stage after aerosol infection with Mycobacterium tuberculosis induced rapid changes in vaginal microbiota in mice. Rapid decrease in both the quantity and diversity of microbiota was noted, and then, partial recovery of normal flora was observed. Changes in vaginal microbiota was detected as soon as in 3-7 days after lung infection, while inflammatory changes appeared by day 35. At the early stage of infection, no signs of inflammation were observed, neither M. tuberculosis nor its DNA were detected in mouse genital organs.

[Characteristics of the Renin-Angiotensin-Aldosterone System in Carriers of Polymorphic Variants of the VDR Gene With Arterial Hypertension and Obesity].

AIM: to study the renin-angiotensin-aldosterone-system (RAAS) in patients with polymorphic variants of the vitamin D receptor gene (VDR), arterial hypertension (AH) and obesity. MATERIALS AND METHODS: We included in this study 98 patients with stage II-III AH and obesity (33 men, 65 women, mean age 61.1±9.9 years and BMI 43.3±5.0 kg/m2). The VDR gene study included genotypes TaqI, BsmI, FokI. After identification of TaqI, BsmI, FokI VDR gene sites we carried out measurements of levels of RAAS markers. RESULTS: We revealed an associative relationship between the presence of allele G of the BsmI site, C/C homozygosity of FokI site of VDR gene and presence of AH in patients with obesity. An increase of renin level was noted only in the homozygous T/T genotype of FokI, no differences in the concentration of aldosterone and angiotensin were detected between any of the studied genotypes. CONCLUSION: Polymorphic alleles and genotypes of the VDR gene can be used as predictors of AH development in obese patients with subsequent characterization of the state of the RAAS system.

Transcription profile analysis of the endometrium revealed molecular markers of the personalized 'window of implantation' during in vitro fertilization.

To determine the most informative markers for assessing the functional state of endometrium during the 'window of implantation' and creating a model for assessment of the readiness of endometrium for embryo implantation. Forty-seven women with tubal infertility and a successful IVF pregnancy participated in the study. Pipelle endometrial sample was performed during the supposed 'window of implantation' in natural cycle with subsequent histological study, and transcriptional profile of genes GPX3, PAEP, DPP4, TAGLN, HABP2, IMPA2, AQP3, HLA-DOB, MSX1, POSTN determined by real-time quantitative polymerase chain reaction (qRT-PCR). Differences in the level of mRNA expression of all the studied genes in the receptive endometrium were found in comparison to the prereceptive one, which allowed us to classify two functional states of the endometrium. The results of histological examination responded to the stage of maturation of the endometrium in 78.7% of cases. Receptive endometrial status can be determined based on the integral evaluation of mRNA expression level of 4 PAEP, DPP4, MSX1, and HLA-DOB genes. The model for determining a personalized `window implantation' is offered for practical application in ART.

[Multislice spiral computed tomography of the heart in dilated cardiomyopathy: possibilities in the verification of myocarditis (in comparison with myocardial biopsy) and in the evaluation of prognosis]. / Mul'tispiral'naia komp'iuternaia tomografiia serdtsa pri sindrome dilatatsionnoi kardiomiopatii: vozmozhnosti v verifikatsii miokardita (po sravneniiu s biopsiei miokarda) i otsenke prognoza.

AIM: To investigate whether intravenous contrast-enhanced multislice spiral computed tomography (computed tomography) (MSCT) versus myocardial morphological examination can diagnose myocarditis and the non-inflammatory causes of dilated cardiomyopathy (DCM) and evaluate prognosis in patients with the latter. SUBJECTS AND METHODS: A study group consisted of 130 patients, including 95 men (46.8±11.9 years), with DCM (mean left ventricular (LV) end-diastolic dimension (EDD), 6.6±0.8 cm; mean LV ejection fraction (EF), 29.8±9.3%; NYHA functional class (FC) III (II; III)). All the patients underwent intravenous contrast-enhanced 320-slice CT of the heart; myocardial morphological examination was made in 48 patients (endomyocardial biopsy in 29 patients, intraoperative biopsy in 7, and autopsy in 9, and study of the explanted heart in 3). In addition, cardiotropic viral DNA in the blood and myocardium and the level of anticardiolipin antibodies were determined; echocardiography (in all the patients), scintigraphy (n = 45), magnetic resonance imaging (MRI) (n = 21), and coronary angiography (CG) (n = 46), and a genetic consultation were performed. A comparison group comprised 20 patients, including 14 men (69.3±9.2 years), with coronary atherosclerosis (40% or more stenoses) according to MSCT findings in the absence of criteria for DCM (mean LV EDD, 4.8±0.5 cm; mean LV EF, 59.4±4.6%). RESULTS: Morphological/comprehensive examination showed that myocarditis as a cause of DCM was diagnosed in 76 (65%) patients; its concurrence with genetic cardiomyopathies was in 17 more patients (17%). MSCT of the heart revealed lower accumulation areas in 2 (1.5%) patients (type 1 based on the proposed rating scale), delayed myocardial contrast agent accumulation (DMCAA) in 81 (62.3%): subendocardial accumulation (type 2) in 8, intramyocardial accumulation in 4 (type 3), subepicardial accumulation in 52 (type 4), and transmural accumulation in 15 (type 5); DMCAA was not noted in 49 patients. DMCAA was not found in the comparison group. As compared with biopsy, the sensitivity, specificity, predictive value of positive and negative results of the tests in detecting active myocarditis for all the types of DMCAA were 77.4, 47.1, 72.7, and 53.3%, respectively; those for types 3-5 of DMCAA were 77.4, 52.9, 75.0, and 56.3%; those in detecting all the morphological types of myocarditis were 68.3, 28.6, 84.8, and 13.3%, and those for types 3-5 were 65.9, 28.6, 84.4, and 12.5%, respectively. Comparison of the data of MSCT and those of comprehensive examination in all the patients with DCM, the diagnostic significance in detecting myocarditis for all the types of DMCAA was 70.6, 67.9, 88.9 and 38.8%, respectively; that for DMCAA types 3-5 was 60.8, 67.9, 87.3, and 32.3%. In the study group, MSCT also identified the non-compacted myocardium (n = 31 (23.8%)), coronary atherosclerosis (n = 31 (23%)), which is confirmed by CG findings in 15 patients. The patients with DMCAA significantly more frequently showed a relationship with previous infection, acute onset, significantly higher NYHA FCs, end-diastolic and end-systolic LV volumes, and insignificantly lower LV EF. During a mean follow-up periods of 12 (6; 37.25) months, the overall mortality rate was 17.7% (23 deaths); the death + transplantation index was 20% (n = 26). All the types of DMCAA were found to be significantly related to prognosis: in the DMCAA group, the mortality rate was 21.5% versus 7.8% in the non-DMCAA group (odds ratio 3.22; 95% confidence interval, 1.02 to 10.21; p < 0.05). CONCLUSION: MSCT with the assessment of delayed contrast enhancement (and simultaneous CT coronary angiography) can be used for the non-invasive diagnosis of myocarditis in patients with DCM, including that in the presence of contraindications to MRI. DMCAA correlates with the presence of myocarditis, its activity, the degree of functional disorders, and prognosis.

Role of Collagen Gene Polymorphisms in the Structure of Early Gestation Loss.

Studies of collagen gene polymorphisms associated with predisposition to early recurrent miscarriages revealed significant differences in the distribution of COL1A1 C-1997A C>A (rs1107946) genotypes and alleles in the group of pregnant patients with early miscarriages in comparison with controls (normal pregnancy). Identification of COL1A1 C-1997A C>A (rs1107946) collagen gene polymorphisms at the stage of pregnancy planning will make it possible to form early miscarriage risk groups for more thorough preparation to gestation and optimization of follow up of this patient population.

Comparison of the Expression Profiles of Immune Response Gene mRNA in Umbilical and Venous Blood of Newborns of the First Day of Life.

The expression of immune response gene mRNA in the umbilical and venous blood were compared in newborns of the first day of life with and without signs of infection. The expression of il1b, il6, il8, il10, il12a, il15, il18, tnfa, tgfb1, tbx21, gata3, foxp3, rorc2, cd45, cd68, cd69, tlr2, tlr4, tlr9, and mmp8 mRNA was evaluated in umbilical and venous blood cells of newborns by reverse transcription real time PCR. In full-term newborns without signs of infection, the expression of il8, tlr2, tlr4, and mmp8 in venous blood was higher than in umbilical blood, while in preterm newborns, the levels of mmp8 transcript were elevated while the levels of tlr9, cd45, and gata3 were reduced. The expression of some markers differed in the umbilical and venous blood and in newborns with congenital infectious disease and without signs of infection.

Peculiarities of the Inflammatory Process in the Reproductive Organs of C57Bl/6 Female Mice with Experimental Tuberculosis.

Intravenous infection of C57Bl/6 female mice with M. tuberculosis H37Rv led to involvement of the lungs and dissemination of the tuberculous infection to the abdominal and pelvic organs. M. tuberculosis were detected in the lungs and spleen in 14, 35, and 90 days and in the uterine horns in 90 days after infection. Morphological analysis of organs showed successive development of exudative necrotic tuberculosis of the lungs, acute and chronic nonspecific inflammation in the reproductive organs (vagina, uterus, and uterine horns). The inflammatory process in the reproductive organs was associated with the development of anaerobic dysbiosis, that was most pronounced in 35 days after infection. Antituberculous therapy was followed by reduction of M. tuberculosis count in the lungs and spleen in 60 and 90 days after infection, eliminatation of M. tuberculosis in the uterine horns, arrest of nonspecific inflammation in female reproductive organs, recovery of the balance between aerobic and anaerobic microflora, and development of candidiasis of the urogenital mucosa.

Profiles of mRNA expression for genes involved in implantation, early and middle phases of secretion stage in human endometrium.

The expression of mRNA of 36 genes involved in implantation was studied by reverse transcription and real-time PCR. Significant differences in mRNA expression during the early and middle stages of the secretion phase were detected for genes mmp7, vegf, il2m, il1ß, il8, il18, tnfα, il10, tgfß, igfbp2, etc.

[HAS-BLED and HEMORR2HAGES Scales in Assessment of Bleeding Risk in Patients on Long-Term Warfarin Therapy].

UNLABELLED: Aim of the study was to elucidate value of HAS-BLED and HEMORR2HAGES scales for prediction bleedings in patients receiving long-term warfarin (W) therapy. MATERIAL AND METHODS: The study involved 119 patients (72 men) aged 60.9 ± 9.6 years with atrial fibrillation or venous thromboembolic complications. Follow up period was 5.6 ± 3.4 years. All bleedings were categorized as 1) single bleeding with INR > 4.0 during the 1st month of W therapy; 2) any single bleeding after 1st month of W therapy; 3) recurrent bleedings. CYP2C9 and VKORC1 (G3673A) genotypic variants were determined by PCR. Patients were divided into low (< 3 points of HAS-BLED scale, n = 58; < 4 points of HEMORR2HAGES scale, n = 109) and high (3 points of HAS-BLED scale, n = 61, ≥ 4 points of HEMORR2HAGES scale, n = 10) bleeding risk groups. RESULTS: There was no relationship between total HAS-BLED, HEMORR2HAGES scores and numbers of all as well as category 1 and 2 bleedings. The difference in bleeding frequency between high and low risk groups was significant only for recurrent bleedings. There were 22 (36.1%) and 5 (8.6%) recurrent bleedings among 61 and 58 patients with high and low-risk HAS-BLED score, respectively (p = 0.0048). Recurrent bleedings also occurred more frequently among patients with high risk (7/10, 70%) compared with low risk (20/109, 18.35%) HEMORR2HAGES score (p = 0.018). Subgroups of high and low bleeding risk according to HAS-BLED and HEMORR2HAGES scores differed only by proportion of patients with recurrent bleedings. High W sensitivity represented by 2*/2*, 2*/3*, 3*/3* CYP2C9 and/or AA VKORC1 homozygosis was detected in 25 of 119 patients. Six of 8 patients (75%) with category 1 bleedings were carriers of any polymorpism. CONCLUSION: HAS-BLED and HEMORR2HAGES scales performed best in predicting recurrent bleedings in patients on long term W therapy. Single bleedings with INR > 4.0 during 1st month of W therapy were associated with reduced W metabolism (AA VKORC1 or/and CYP2C9 allelic variants 2*/2*, 2*/3*, 3*/3*).

[HAS-BLED and HEMORR2HAGES Scales in Assessment of Bleeding Risk in Patients on Long-Term Warfarin Therapy].

Aim of the study was to elucidate value of HAS-BLED and HEMORR2HAGES scales for prediction bleedings in patients receiving long-term warfarin (W) therapy. MATERIAL AND METHODS: The study involved 119 patients (72 men) aged 60.9+/-9.6 years with atrial fibrillation or venous thromboembolic complications. Follow up period was 5.6 +/-3.4 years. All bleedings were categorized as 1) single bleeding with INR>4.0 during the 1st month of W therapy; 2) any single bleeding after 1st month of W therapy; 3) recurrent bleedings. CYP29 and VKORC1 (G3673A) genotypic variants were determined by PCR. Patients were divided into low (<3 points of HAS-BLED scale, n=58; <4 points.

Association of ESR1 gene polymorphism with preterm rupture of fetal membranes.

We examined 179 patients with and without preterm rupture of fetal membranes. The mothers and their newborns have been genotyped by two polymorphic loci of estrogen receptor α (ESR1) gene: -397T > C[PvuII] (rs2234693) and -351A > G[XbaI] (rs9340799). The CG haplotype of the fetus should be regarded as a risk factor of preterm rupture of fetal membranes, while haplotype TA as a protective factor. Genotype -351A/A is a marker of the protective haplotype in the fetus, while genotype -397C/C is a marker of the risk haplotype, which can be used in combined analysis of both markers. These data attest to an important role of fetal genotype in the formation of genetic predisposition to preterm rupture of fetal membranes.

Actn3 genotype is associated with testosterone levels of athletes.

UNLABELLED: α-Actinin-3 (ACTN3) has been proposed to regulate skeletal muscle differentiation and hypertrophy through its interaction with the signalling protein calcineurin. Since the inhibition of calcineurin potentiates the production of testosterone, we hypothesized that α-actinin-3 deficiency (predicted from the ACTN3 XX genotype) may influence serum levels of testosterone of athletes. OBJECTIVE: To investigate the association of ACTN3 gene R577X polymorphism with resting testosterone levels in athletes. METHODS: A total of 209 elite Russian athletes from different sports (119 males, 90 females) were genotyped for ACTN3 gene R577X polymorphism by real-time PCR. Resting testosterone was examined in serum of athletes using enzyme immunoassay. RESULTS: The mean testosterone levels were significantly higher in both males and females with the ACTN3 R allele than in XX homozygotes (males: RR: 24.9 (5.7), RX: 21.8 (5.5), XX: 18.6 (4.9) ng · mL(-1), P = 0.0071; females: RR: 1.43 (0.6), RX: 1.21 (0.71), XX: 0.79 (0.66) ng · mL(-1), P = 0.0167). CONCLUSIONS: We found that the ACTN3 R allele was associated with high levels of testosterone in athletes, and this may explain, in part, the association between the ACTN3 RR genotype, skeletal muscle hypertrophy and power athlete status.

[Idiopathic arrhythmias: possibilities of complex nosological diagnosis, and differentiated treatment].

AIM: of the study was to elucidate nosological nature of "idiopathic" arrhythmias by means of complex clinical-morphological examination and to assess efficacy of differentiated (including etiotropic and pathogenetic) treatment. MATERIAL AND METHODS: We examined 190 patients (117 women, mean age 45.33 ± 14.84 years) with "idiopathic" arrhythmias: atrial fibrillation (38.9%) (AF,) and flutter (11.1%), supraventricular (44.7%) and ventricular (55.3%) extrasystoles (SVE and VE), bouts of ventricular tachycardia (15.8%), atrioventricular block (22,6%) et al. Mean number of antiarrhythmic drugs per patient was 3 (from 1 to 8). Examination included Holter ECG monitoring, echocardiography, determination of anticardiac antibodies (97.4%) and markers of cardiotropic viruses (87.4%), treadmill test (26.3%), transesophageal cardiac pacing (12.1%), electrophysiological investigation (10%), multispiral computed tomography (22.1%), magnetic resonance tomography (21.6%), scintigraphy (27.4%), coronary angiography (10.0%), endomyocardial biopsy (EMB) (10.0%), DNA diagnostics (8.9%). RESULTS: EMB revealed immune-inflammatory (myo/endocarditis, systemic/myocardial vasculitis) or genetic pathology in 78.9 and 21.1% of cases, respectively. Level of anticardiac antibodies (including specific antinuclear factor) most closely correlated with EMB findings. On the basis of comparison of EMB data with data of complex examination we created algorithm of nosological diagnostics in "idiopathic" arrhythmias. According to nosology all patients were distributed in the following way: 1) chronic infectious-immune myocarditis (n=144, 75.7%), morphologically verified in 14, viral in 27 patients; 2) genetic cardiomyopathy (n=15, 7.9%), morphologically verified in 4, virus positive in 1 (arrhythmogenic right ventricular dysplasia, non-compaction myocardium, Fabri disease, Brugada syndrome, undetermined); in 4 patients mutations in plakophilin 2, desmoglein, desmin, -galactosidase A genes were found; 3) combination of genetic diseases with myocarditis (n=18; 9.5%) including viral (n=3); 4) isolated myocardiodystrophy (tonsillogenic< dyshormonal, n=3, 1.6%); 5) proper idiopathic arrhythmias (n=10, 5.3%). Therapy of myocarditis included antiviral (43.2%) and immunosuppressive (76.3%) drugs. Cardiotropic and antiarrhythmic therapy was also administered. Only in patients with myocarditis it was possible to withdraw effective antiarrhythmic (16.7%) and to improve effect of previously ineffective drugs. Surgical treatment (implantation of pacemaker or cardioverter-defibrillator, radiofrequency ablation) was more frequently used in patients with genetic (39.4%) and idiopathic arrhythmias (53.8%) than in patients with myocarditis (16.0%). CONCLUSION: Etiology of idiopathic arrhythmias can be established in most cases. Their main causes are immune-inflammatory diseases, genetic cardiomyopathies and their combination. Therapy of myocarditis improves antiarrhythmic activity of treatment, in some patients allows to withdraw antiarrhythmic drugs, decrease requirements in surgical treatment and to optimally prepare patients to radiofrequency ablation.

[Possibilities myocardial biopsy in the diagnosis of myocarditis verification in patients with idiopathic arrhythmias].

UNLABELLED: Aim of the study was to elucidate nosological nature of "idiopathic" arrhythmias by means of right ventricular endomyocardial biopsy (EMB) and to assess effect of etiotropic and pathogenetic treatment. MATERIAL AND METHODS: We included into this study 19 patients (mean age 42.6 +/-11.3 years, 9 women) with atrial fibrillation (AF, n = 16), supraventricular (n = 10) and ventricular (n = 4) extrasystoles (SVE and VE), supraventricular (n = 2) and ventricular (n = 1) tachycardia (SVT and VT), left bundle branch block (LBBB, n = 2), atrioventricular block (n = 2) without structural changes of the heart. In addition to standard examination we performed the following tests: determination of IgG to herpes and Coxsackie B virus, polymerase chain reaction (PCR) for DNA detection of human herpesviruses 1, 2, and 6, Epstein-Barr virus, Varicellae-zoster virus (human herpesvirus 3) and cytomegalovirus in blood; determination of anticardiac antibodies; EMB with subsequent PCR-diagnostics including that of parvovirus B19 and pathomorphological study. DNA diagnostics (n = 4), coronary angiography (n = 6), skin biopsy (n = 1) and some other studies were also performed when indicated. RESULTS AND CONCLUSIONS: Histological picture was abnormal in all cases. Nosological diagnosis was established in all patients: infectious-immune myocarditis (n = 11), parvovirus positive endomyocarditis (n = 1); systemic vasculitis (n = 2); myocardial vasculitis (n = 1), Fabri disease (n = 1), arrhythmogenic right ventricular dysplasia (ARVD, n = 1), undetermined genetic cardiomyopathy (n = 2). Level of various anticardiac antibodies including antinuclear factor with bovine heart antigen was most valuable for diagnosis of myocarditis (sensitivity 78.6%, prognostic value of positive result 91.7%). The following therapy was used in patients with myocarditis/vasculitis: intravenous or oral acyclovir (n = 10), gabreglobine (n = 2), meloxicam (n = 12), hydroxychloroquine (n = 15 for 15 [7.0; 24.] months), glucocorticosteroids (n = 14 for 18 [4.0; 25.5] months), azathioprine (n = 2). Mean duration of follow up was 4 years (48 [31; 62] months). At baseline 62.5% of patients with AF were resistant to all antiarrhythmic drugs. Treatment of myocarditis resulted in significant reduction of mean frequency of attacks of AF from 8 to 3 points, more than in 40% of patients AF emerged less than once a month and 1 patient had no attacks at all. Disappearance of tachycardia dependent LBBB was also noted. Cardioverter defibrillator and cardiac pacemaker were implanted to patients with ARVD and Fabri disease, respectively. EMB helped to establish immunoinflammatory and genetic diseases as causes of idiopathic arrhythmias (in 78.9 and 21.1% of patients, respectively). Antiviral immunosuppressive therapy of myocarditis allowed to increase efficacy of antiarrhythmic therapy in resistant patients and when necessary to optimize their preparedness to interventional treatment.

[Noncoronary dilated cardiomyopathy after reverse remodeling heart surgery].

We present here analysis of surgical treatment of 24 patients (5 women, 19 men, age 20-75, mean age 50.7 +/- 2.5 years) with dilated cardiomyopathy (DCM) operated during the period from 2008 to 2013. Duration of the disease ranged from 4 months to 12 years (mean 49.4 +/- 7.5 months). According to symptoms and results of 6-minute walk test 3 patients (13%) had heart failure NYHA class III and 21 patients (87%)--NYHA class IV. Average end-diastolic left ventricular size was 7.4 +/- 0.18 cm (6.0-9.2 cm), ejection fraction--26.7 +/- 2.1% (13-47%), mean pulmonary artery pressure 54.9 +/- 2.9 mm Hg (35-80 mmHg). All patients underwent organ-conserving surgery aimed at reverse remodeling of the heart. Surgery was accompanied with implantation of implantable cardioverter defibrillator in 3 patients and/or cardiac resynchronization therapy device in 6 patients. Two patients (8.3%) died during hospitalization of hemodynamically significant ventricular arrhythmias; seven patients (29.2%) died in the late postoperative period. The results of the analysis indicate that reverse-remodeling surgery may be effective in patients with DCM of any age group with preserved reserves of the liver, kidney, and lung function in the absence of active myocarditis. Further observations are needed to determine the place of this operation in the protocol of treatment of patients with DCM.

Protamine and fertilin mRNA: potential biomarkers of assisted reproductive technology outcomes.

We studied the relationship between the levels of protamines 1 and 2 (PRM1 and PRM2) and fertilin-ß (ADAM-2) mRNA expression and outcomes of infertility treatment using assisted reproductive technologies was studied. Analysis of the relationships between the outcomes of in vitro fertilization and embryo transfer and profiles of the expression of seminal genes PRM1, PRM2, ADAM-2 mRNA, evaluated by reverse transcription quantitative PCR was carried out in 79 couples. Significant differences in the expression of seminal PRM1, PRM2, ADAM-2 mRNA were detected in couples with different outcomes of in vitro fertilization and embryo transfer. The levels of seminal gene expression are potential predictors of the efficiency of in vitro fertilization and embryo transfer.

[Clinico-morphological and molecular-genetic characteristic of the miometrium with failure of the uterine scar after the Cesarean section at women with undifferentiated forms of connective tissue dysplasia].

Connective tissue state, its strength, is actual problem especially in the moment of labor because the weakness of labor activity or accelerated labor can be in depending on its consistency and elasticity. In addition, connective tissue is very important in the involution of the uterus after labor or wounds healing. Clinico-morphological and molecular-genetic investigation of 90 patients with undifferentiated forms of connective tissue dysplasia (uCTD) has been done. Reparation of tissue at patients with uCTD had a number of peculiarities, such as fibromuscular scar formation by substitution mechanisms with the laminin deficiency in the basic capillar membrane and extracellular matrix, accumulation of III and IV types of collagen, low expression of VEGF in the stromal cell and polymorphism of the alpha estrogen receptor gene. This immunohistochemical changes correlated with focuses of connective tissue disorganization as mucoid swelling, fibrinoid changes and hyalinosis, as well pathology of the microvasculature, resulted in chronic ischemia of the tissue. The disorganization is connected with disturbed reparation as a result of the genetically determined polymorphism of alpha and beta estrogen receptors. uCTD in pregnant women is prognostically significant for selection of way of delivery.

[Noncompaction myocardium as a primary phenomenon or consequence of myocardial dysfunction: clinical masks of the syndrome].

Noncompaction myocardium (NCM) is a genetic heterogeneous primary cardiomyopathy which affects both children and adults and can be either isolated or combined with other congenital heart disorders. It has common pathogenesis of symptoms but is distinguished by pronounced clinical polymorphism. We have observed 25 adult patients (15 men, 10 women aged from 20 to 62 years, mean age 42.9+/-13.3 years) with NCM syndrome. Heart failure have been found in 96% of patients (functional class [FC] I in 7, II - in 6, III in 7, and IV - in 4 patients). Ninety two percent of patients have ventricular extrasystoles, 32% - atrial fibrillation, 28% - FC I-III angina. Mean end diastolic left ventricular dimension is 6.5+/-0.8cm, ejection fraction 29.7+/-13.0%, mean pulmonary artery pressure - 42.6+/-13.5 mm Hg. Intracardiac thrombosis have been found in 24% of patients. In 7 patients morphological study of myocardium has been performed. NCM syndrome was diagnosed at initial investigation just in 1 case. We distinguished the following clinical masks (variants of diagnosis) of NCM: 1) clinically not manifest, is revealed at accidental examination (4%); 2) exists under mask of "idiopathic" rhythm disturbances (8%); 3) has a mask of ischemic heart disease; 4) is revealed in patients with acute or subacute myocarditis (12%); 5) has a mask of dilated cardiomyopathy (52%); 6) NCM in patients with other primary cardiomyopathies (hypertrophic, restrictive, genetic myopathy, arrhythmogenic right ventricular dysplasia). Combination of NCM with congenital heart defects has been found in 20% of patients. In 56% of cases myocarditis was diagnosed (it was viral in no less than 44%). Only in 32% of patients it is possible to consider presence of isolated NCM syndrome. This paper contains discussion of problems of diagnostics (including morphological) and treatment in the presented group of patients, significance of myocarditis for development of decompensation, role of NCM in patients with other primary cardiomyopathies, possibility of compensatory (secondary) character of NCM in severe systolic dysfunction.