[Early Markers of Cardiovascular Risk in Women With Hereditary Burdening by Cardiovascular Diseases].

PURPOSE: to identify early markers of development of cardiovascular diseases (CVD) in women. MATERIALS AND METHODS: Female firstdegree relatives from 39 families formed 2 groups: families (n=19) containing mothers with arterial hypertension (AH) (group 1) and healthy daughters (group 1a); families (n=20) containing practically heathy mothers (group 2) and healthy daughters (group 2a). We assessed data of anamnesis, including registration of cardiovascular risk factors, and family history of CVD. Examination included registration of anthropometric parameters, automatic and manual measurement of intima-media thickness (IMT) and resistance indexes of brachiocephalic arteries (BCA). We also determined cardio-ankle vascular index (CAVI), ankle-brachial index (ABI), and measured magnitude of ß-adrenoreception of membranes (ß-ARM) of erythrocytes in micro-quantities of venous blood. RESULTS: Mothers in both groups of families had excessive body mass or obesity. Mothers of group 1 had more pronounced signs of abdominal obesity (AO). They also had abnormalities of IMT and sings of subclinical atherosclerosis of BCA. CAVI in this group was significantly higher than in group 2. In group 1a median BMI (25.5 kg/m2) and waist/hip ratio were significantly higher than in group 2a. Daughters of group 1a contrary to group 2a had abnormalities of vascular wall: increased automatically measured IMT of carotid arteries and elevated CAVI. Arterial pressure and heart rate (HR) in group 1a were within limits of physiological norm but significantly higher than in group 2a. All included women had elevated ß-ARM values but in group 1a this parameter was significantly higher than in group 2a and moderately correlated with HR. CONCLUSIONS: Risk factors of CVD development in women are AH, AO, high activity of the sympathoadrenal system. These factors provoke changes of vascular wall (elevation of its stiffness and early subclinical atherosclerosis). In daughters of mothers with AH important prognostic components of CVD risk in addition to family history of CVD are AO, systolic blood pressure (BP) >120 mm Hg, diastolic BP >78 mm Hg, HR approaching upper limit of physiological norm, and high CAVI (indicator of vascular wall stiffness).

Cardiovascular disease and associated comorbid conditions as determinants of adverse perinatal outcomes in pregnancy - an analysis of the results of the register of pregnant BEREG.

AIM: the Aim of the BEREG Registry was to analyze the prevalence and structure of cardiovascular diseases, associated comorbid conditions and assess their effects on pregnancy and perinatal outcomes in real clinical practice. MATERIALS AND METHODS: In Tula city regional perinatal center the observation study named "Assessment of the clinical condition of the pregnant women with cardiovascular disease during gestation, at child delivery, at the early postpartum period and at twelve months after childbirth and assesment of perinatal outcomes, condition of the fetus and the newborn and the quality of treatment of these patients groups.  All eligibly pregnant women hospitalized in 2014 to "Tula regional perinatal center" have been recruited in the Registry. Clinical and demographic data at admission, obstetric history, laboratory and instrumental examination data, previous medical history have been investigated. The following endpoints were evaluated: maternal mortality, death of the fetus and newborn baby; preeclampsia or/and eclampsia, heart failure, arrhythmia, thromboembolism events.  Statistical processing of obtained data was carried out using the software package STATISTICA 10.0 (StatSoft, USA). RESULTS: The study included 3214 women delivered babies in the perinatal center in 2014, of which 691 (21,4%) were diagnosed with cardiovascular disease (CVD) in most cases (451 women, 65,9%) - these were different clinical variants of arterial hypertension (AH). Five women (0.7%) had acquired and 23 women ( 3.3%,) congenital heart defect, non-significant heart development abnormities were found in 80 subjects, (11.6%). and Cardiac arrhythmias and conductivity disturbance have been revealed in 116 and 16 cases (16.8% and 2.3%) correspondingly. Patients with CVD were significantly older than women without CVD and more often had a variety of disorders of carbohydrate metabolism, overweight, obesity and chronic varicose disease of the lower extremities. Pregnancy in women with CVD significantly more often was complicated by the threat of interruption, placental insufficiency, preterm and operative babies delivery. Arterial hypertension as well as obesity, placental insufficiency and threatened miscarriage became prognostically unfavorable conditions that contributed of premature birth and fetal death. Fetal death or newborn babies death took place in 1,3% of all the subjects enrolled. In this cohort antenatal death have been registered in 43,2%, intrapartum one in 2.3% and neonatal death in 54.5%. CONCLUSION: Negative prognostic factors for low birth-weight babies were: placental insufficiency, various clinical variants of AH, obesity and infectious diseases; less input had endocrine diseases and risk of abortion. Adverse factors for the fetus death or newborn death were different clinical variants of arterial hypertension and the risk of abortion in any trimestre of pregnancy.

[A PERSPECTIVE CULTURAL MODEL FOR CONTROL OF BIOLOGICAL ACTIVITY OF HUMAN INTERFERONS].

AIM: Study species specificity of human lymphocyte interferon alpha in vitro in cell cultures of swine origin for expansion of cell line spectrum for interferon titration and control of newly created interferons and interferon-like preparations in vivo in mini-pig model. MATERIALS AND METHODS: Cell cultures of various species origin were used: Vero (monkey kidney), MDBK (bull kidney), HEK 293T (human embryo kidney), PK-15 (swine kidney), SPEV(swine embryo kidney), PTP (swine testicles), MDCK (canine kidney), RK-13 (rabbit kidney). Human lymphocyte interferon alpha (hINF-alpha) from Biomed company (1000 IU/ml), established in MDBK cells, was tested. Vesicular stomatitis virus (Indiana strain) was used. Human plasma was obtained from heparin-treated venous blood in the process of human peripheral blood lymphocyte isolation in medium for lymphocyte separation (Ficoll with a density of 1.077 g/cm3). RESULTS: Vesicular stomatitis virus, adapted to Vero cells, was established to have the least active reproduction in Vero and MDBK and reproduces more actively in cell of swine origin by 0.25 - 0.75 lg TCD50. At the same time, virus, adapted to cells of swine origin, reproduces more actively by 2 - 3 lg TCD50 in both cells of swine origin and Vero and MDBK. CONCLUSION: A possibility of titration of hINF-alpha in cells of swine origin was shown for both 100 doses of the indicator virus and low virus doses (5 and 10). This allows to determine low titers of hINF-alpha in blood plasma as one of the important indicators of interferon status--sera hINF-alpha.

Fetal skeletal dysplasias in a tertiary care center: radiology, pathology, and molecular analysis of 112 cases.

Fetal skeletal dysplasias are a heterogeneous group of rare genetic disorders, affecting approximately 2.4-4.5 of 10,000 births. We performed a retrospective review of the perinatal autopsies conducted between the years 2002-2011 at our center. The study population consisted of fetuses diagnosed with skeletal dysplasia with subsequent termination, stillbirth and live-born who died shortly after birth. Of the 2002 autopsies performed, 112 (5.6%) were diagnosed with skeletal dysplasia. These 112 cases encompassed 17 of 40 groups of Nosology 2010. The two most common Nosology groups were osteogenesis imperfecta [OI, 27/112 (24%)] and the fibroblast growth factor receptor type 3 (FGFR3) chondrodysplasias [27/112 (24%)]. The most common specific diagnoses were thanatophoric dysplasia (TD) type 1 [20 (17.9%)], and OI type 2 [20 (17.9%)]. The combined radiology, pathology, and genetic investigations and grouping the cases using Nosology 2010 resulted in a specific diagnosis in 96 of 112 cases.

Temporal lobe dysplasia: a characteristic sonographic finding in thanatophoric dysplasia.

OBJECTIVE: To determine the incidence of temporal lobe dysplasia (TLD) detected on prenatal ultrasound in thanatophoric dysplasia (TD) over an 11-year period in a tertiary referral center. METHODS: An 11-year retrospective review of perinatal autopsies from 2002 to 2013 was performed to identify cases of TD. The ultrasound images and corresponding reports of all TD cases were examined for the presence of TLD. The same set of images subsequently underwent a retrospective review by a perinatal radiologist with knowledge of the features of TLD to determine whether they could be identified. RESULTS: Thirty-one cases of TD underwent perinatal autopsy, and prenatal ultrasound imaging was available for review in 24 (77%). Mean gestational age at diagnosis of TD was 21.3 (range, 18-36) weeks. TLD was identified and reported in 6/24 (25%) cases; all six cases occurred after 2007. Retrospective interpretation of the ultrasound images identified features of TLD in 10 additional cases. In total, 16/24 (67%) cases displayed sonographic evidence of TLD. Temporal trends showed that TLD features were present in 50% (5/10) of all TD cases between 2002 and 2006 and in 79% (11/14) of those detected between 2007 and 2013. CONCLUSIONS: At present, the detection rate of TLD by ultrasound is low but may be increased by modified brain images that enhance visualization of the temporal lobes. Prenatal identification of TLD may help in the prenatal diagnosis of TD and thus provide more accurate prenatal counseling and guide molecular investigations to confirm the specific diagnosis of TD.

[Monoclonal antibodies to rubella virus glycoprotein E1].

AIM: To obtain monoclonal antibodies (MCAs) to glycoprotein E1 of rubella virus, to assess their immunochemical characteristics and ability to use fluorescent MCA for rapid identification of rubella virus. MATERIALS AND METHODS: Rubella virus strain C-74 (Moscow), vaccine strains "Orlov" (Saint-Petersburg), Wistar RA 27/3 (USA) as well as strain Judith (Germany) were used. Viral antigens were obtained using diploid cells L-68 and cell lines VNK-21-F and Vero E6. MCAs were produced by conventional method and their isotype was determined: Immunoblotting, immunoenzume assay (IEA), hemagglutination inhibition assay (HIA) and immunofluorescence assay (IFA) were performed. RESULTS: Five monoclonal antibodies--Kh-252.1, Kh-347.2, Kh-183.3, Kh-214.4, Kh-187.5--to antigens of rubella virus strain C-74 were obtained. Isotypes of these antibodies were determined and their reactivity with native and denaturated antigens of other strains ("Orlov", Wistar RA 27/3, Judith) was characterized. IEA showed that all MCAs interacted with rubella virus glycoprotein E1 at high titers ranging from 1/1600 to 1/200,000. Immunoblotting demonstrated that 4 MCAs (Kh-252.1, Kh-347.2, Kh-183.3, Kh-214.4) had aforementioned feature. MCAs inhibited hemagglutinating activity of Judith strain in titer from 1/16 to 1/1024 in HIA. FITC conjugate of MCA Kh-347.2 (most sensitive variant) allowed to detect rubella virus in infected Vero E6 cells after 24 hours since infection, whereas FITC conjugates of 3 MCAs (Kh-183.3, Kh-214.4, Kh-187.5)--after 72 hours since infection. CONCLUSION: Use of FITC conjugates of MCAs is a perspective tool for identification of rubella virus glycoprotein E1 in infected cell cultures and nasopharyngeal swabs.

Erythropoiesis and iron metabolism biorhythms in children with chronic pyelonephritis.

Circadian dynamics of ferritin, serum iron, and MDA concentrations, ineffective, normal, and terminal kinetic populations of the erythron were studied in healthy girls aged 7-9 years and girls suffering from chronic pyelonephritis. The production of highly active macrocyte population, descending from terminal erythropoiesis, was increased during pyelonephritis remission, which determined reduction of serum iron concentration during the morning hours and leveling of its circadian rhythm because of high utilization of the trace element. Progressive reduction of erythrocyte count and hemoglobin content during the active phase of pyelonephritis correlated with the increase in the population of microcytes with low activity of glucose-6-phosphate dehydrogenase and short life span, paralleled by an appreciable increase in ferritin and MDA concentrations during the evening hours. Stimulation of alternative erythron kinetic types (terminal and ineffective) underlies these changes.

Circadian dynamics of monocyte phagocytic activity in women during lactation complicated by iron deficiency.

Biorhythms of phagocytic activity of peripheral blood monocytes were studied during lactation in healthy women and in women with iron deficiency. Circadian organization of monocyte function was characteristic of healthy nursing women. Strain in the system was associated with elevation of the mean circadian values for reserve potential of the absorption and digestive capacity of phagocytes. Circadian rhythms of the phagocytic and digestive capacity of peripheral blood monocytes were leveled during lactation complicated by iron deficiency. Decreased coefficient of the parameters activation is an early manifestation of latent iron deficiency. Decrease in the basic function parameters and reserve potential are directly related to the decrease in serum ferritin concentration.

Diurnal variations in qualitative composition of breast milk in women with iron deficiency.

Biorhythms of iron metabolism in healthy women and patients with iron deficiency were studied during lactation. Healthy nursing women were characterized by circadian variations in the concentrations of iron, alpha-tocopherol, and malonic dialdehyde in breast milk. Diurnal variations in iron concentration, antioxidant potential, and lipid peroxidation in breast milk depended on iron metabolism in nursing women. Iron deficiency was accompanied by a decrease in the concentrations of alpha-tocopherol and iron, increase in malonic dialdehyde content, and suppression of circadian variations in these parameters in breast milk.

[Behavioral and electrophysiological analysis of the choline-positive effect of nootropic dipeptide acylproline (GVS-111)]. / Povedencheskii i élektrofiziologicheskii analiz kholino-pozitivnogo deistviia nootropnogo atsil-prolin dipeptida (GVS-111).

The behavioral experiments using a passive avoidance learning model showed that the new cognition-enhancing acyl-prolyn containing dipeptide GVS-111 promotes recovery of the test performance in animals with a long-term memory deficit caused by the M-cholinolytic scopolamine (1 mg/kg/day scopolamine for 20 days, followed by 0.5 mg/kg/day GVS-111 for 10 days). At the same time, GVS-111 increased the duration of tremor induced by the M-cholinomimetic arecoline. The results of electrophysicological experiments showed that GVS-111 in a concentration range from 10(-11) to 10(-9) M increased amplitude of the neural response to acetylcholine (Ach) microappications in 75% of the isolated neurons of Helix Pomatum and produced a predominantly facilitating effect upon the endoneuronal pacemaker activity. The effect of GVS-111 upon the Ach response in a part of neurons was attenuated or even blocked by scopolamine, and in the other neurons--by the N-cholinolytic d-tubocurarine. This fact indicates that both muscarinic and nicotinic receptors are involved in the mechanism of the cholino-sensitizing action of GVS-111 upon the neuronal activity.

[Expression of receptors for human alpha- and gamma-interferons on the surface of peripheral blood mononuclear cells in viral infections]. / Ekspressiia retseptorov dlia chelovecheskikh alpha- i gamma-interferonov na poverkhnosti mononuklearnykh kletok perifericheskoi krovi pri virusnykh infektsiiakh.

Expression of receptors on peripheral blood mononuclears of donors and patients with viral infections during therapy was studied using FITC-labeled monoclonal antiidiotypical antibodies with the "internal image" of human alpha- and gamma-interferons and monoclonal antibodies to these interferons. Activation of the immune system caused by infection modifies the expression of interferon receptors and leads to appearance of membrane-bound interferons, mainly gamma-interferon.

[The protective effect of monoclonal anti-idiotypic antibodies in experimental herpes infection]. / Protektivnyi éffekt monoklonal'nykh antiidiotipicheskikh antitel pri éksperimental'noi gerpeticheskoi infektsii.

The protective effect of monoclonal anti-idiotypic antibodies m(anti-ID)Abs, simulating the biologic effects of human alpha interferons, were studied in male guinea pigs with genital herpes simplex. Therapeutic effect of m(anti-ID)Abs daily applied as liquid dosage form and as suppositories+ was assessed. Experiments demonstrated that m(anti-ID)Abs in liquid dosage form to a different measure decreased the severity of urogenital infection in guinea pigs and that m(anti-ID)Abs-25 completely prevented the development of grave infection.

[The role of the liver in regulating the blood iron biorhythms of rabbits with acute alcoholic intoxication]. / Rol' pecheni v reguliatsii bioritmov sideremii u krolikov pri ostroi alkogol'noi intoksikatsii.

Experiments with male California rabbits were carried out different intervals of acute alcohol intoxication induced by intragastric administration of 40% ethanol solution in a dose of 10 ml/kg to examine daily changes of concentration of iron, alpha-tocopherol and lipid peroxidation products in the blood plasma from vena portal and vena hepatis. Acute alcohol intoxication was demonstrated to be accompanied by inversion in temporal organization of lipid peroxidation products, sideremia and alpha-tocopherol levels in the blood of vena hepatis. The invariability of the circadian rhythms of iron, alpha-tocopherol and lipid peroxidation products levels in vena portal blood a considered to prove participation of the liver in regulation of iron metabolism temporal organization in California rabbits with acute alcohol intoxication.

[Seasonal characteristics of the circadian rhythm of peripheral blood leukocyte content in Wistar rats]. / Sezonnye osobennosti tsirkadiannykh ritmov soderzhaniia leikotsitov v perifericheskoi krovi u krys linii Vistar.

In Wistar rats, the seasonal variability of acrophase position, mesor value and circadian rhythm amplitudes of total leukocyte count, as well as of percentage and absolute lymphocyte count was revealed. The leukocyte count and absolute lymphocyte content were found highest in spring, while eosinophils--in autumn, neutrophils and monocytes--in winter.

[Daily dynamics of iron excretion with murine in experimental hepatosis]. / Sutochnaia dinamika ékskretsii zheleza s mochoi pri éksperimental'nom gepatoze.

Experimental hepatosis induced by intragastric administration of CCl4 was revealed to be accompanied by changes in temporal organization of lipid peroxidation, sideremia and iron excretion with urine. Even at early stages of organ lesions, the activation of free-radical lipid oxidation and rearrangement of sideruria circadian rhythm were found to result in a substantial and stable increase in mesor of the trace element excretion with urine in spite of a statistically significant decrease in water release.

[The antiproliferative activity of monoclonal anti-idiotypic antibodies imitating the biological effects of human alpha-interferons]. / Antiproliferativnaia aktivnost' monoklonal'nykh antiidiotipicheskikh antitel, imitiruiushchikh biologicheskie éffekty chelovecheskikh interferonov al'fa.

The experimental data from the study of antiproliferative activity (AP-activity) of monoclonal antiidiotypic antibody (mono-Ai-At) imitating biological effects of human alpha interferons (h-IF-alpha) are presented. The mono-Ai-At present in the ascitic and culture fluids (the culture fluid was obtained from cultivation of hybrid cells immobilized in alginate-gelatine gel) were shown to inhibit propagation of IF-sensitive continuous cells from normal and tumor tissues. The AP-activity of mono-Ai-At was found to be within the range of their antiviral activity. It is concluded that mono-Ai-At may be used as a new experimental model for investigation of h-IF-alpha biological effects.

[Balloon dilatation of aortic coarctation]. / Ballonnaia dilatatsiia koarktatsii aorty.

Endovascular balloon dilatation of coarctation of the aorta is a manipulation for radical correction of the anomaly with an evident hemodynamic effect in patients with the isolated form, in combination of coarctation of the aorta with aortic stenosis, and in atypical forms of the anomaly. Up to 90% of good immediate results were produced among these patients. Balloon dilatation may also be conducted in recoarctation after the traditional surgical management. Being devoid of some of the negative factors of the accepted methods of treatment, endovascular angioplasty is a sparing and a relatively safe method. Paradoxical hypertension does not develop as a rule. Rare complications in the zone of the approach were encountered. Balloon dilatation may be combined with endovascular correction of other anomalies, and may be repeated many times. In recoarctation and atypical forms of the anomaly balloon dilatation helps in avoiding complex and dangerous operations using the traditional methods. Coarctation in the form of a diaphragm is the most "favourable" type of the anomaly for balloon dilatation. The operation is also indicated in coarctation in patients with hypoplasia of the arch and isthmus, despite its palliative character.

[Monoclonal anti-idiotypic antibodies simulating the biological effects of human alpha-interferons]. / Monoklonal'nye antiidiotipicheskie antitela, imitiruiushchie biologicheskie éffekty chelovecheskikh al'fa-interferonov.

The method of somatic hybridization was used to generate a panel of hybridomas producing monoclonal anti-idiotypic antibodies (mono-Ai-Ab) imitating biological effects of human alpha-interferons (hIF-alpha). Induction of syngeneic anti-idiotypic antibodies in BALB/c mice was achieved with monoclonal antibodies (MCA) IF-39 capable of neutralizing three kinds of hIF-alpha (lymphoblastoid, leukocyte, genetic-engineering). The screening of mono-Ai-Ab was done by determinations of antiviral activity (AV-activity) of supernatants from growing hybrid cell cultures caused by the cytopathic effect of 10-100 doses of mouse encephalomyocarditis virus (MEMC) by a micromethod in Vero cells grown in 96-well plates. Mono-Ai-Ab were found to neutralize MCA IF-39 and not to bind with immunosorbent of staphylococcal reagent containing protein A and BALB/c mouse immunoglobulins. It was shown that mono-Ai-Ab possessed AV-activity against MEMC and vesicular stomatitis viruses and were not inferior in this activity to commercial preparations of leukocyte IF-alpha. Mono-Ai-Ab had tissue species-specificity triggering the mechanism of AV-activity in human and simian cells as well as bovine kidney cells (MDVK line) imitating hIF-alpha in this effect.

[Monoclonal antibodies to natural human gamma-type interferon]. / Monoklonal'nye antitela k prirodnomu chelovecheskomu interferonu tipa gamma.

Nine hybridomas producing monoclonal antibodies (MCA) to natural human gamma interferon (IF-gamma) were generated. BALB/c mice were immunized with nonpurified IF-gamma preparation synthesized by lymphoid cells of the peripheral blood of donors in response to induction with staphylococcal enterotoxin A. For the first time somatic hybridization was done with the use of a medium with a high content of HEPES which maintained hybridomas viable for a long period of time. Out of 9 hybridomas, two (-gamma 6.1 and gamma-8.1) were shown to produce MCA with a high binding activity in the enzyme immunoassay. The same MCA effectively neutralized the biological activity of natural IF-gamma.