Antibody to Marinobufagenin Reverses Placenta-Induced Fibrosis of Umbilical Arteries in Preeclampsia.

Background: Previous studies implicated cardiotonic steroids, including Na/K-ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE). Immunoneutralization of heightened MBG by Digibind, a digoxin antibody, reduces blood pressure (BP) in patients with PE, and anti-MBG monoclonal antibody lessens BP in a rat model of PE. Recently, we demonstrated that MBG induces fibrosis in cardiovascular tissues via a mechanism involving inhibition of Fli-1, a nuclear transcription factor and a negative regulator of collagen-1 synthesis.

[On the discontinuity of the annuity curves in Drosophila melanogaster Canton-S strain. IV. Effect of low temperature on the early imaginal stage].

We tested the effect of low temperature (18-20 °C) applied at the 13-22 days of imago life. We detected prolongation of individual life span. The effect is due to prolongation of the first phase of the annuity curve and thus to further delay of the next ones.

Effects of placental tissue secretory products on the formation of vascular tubules by EA.Hy926 endothelial cells.

The formation of vascular tubules by EA.Hy926 endothelial cells was studied in the presence of placental secretory products from women with normal gestation at early and late periods and with gestosis. The factors secreted by placental tissues at the early stages of placental development stimulated the branching angiogenesis, while the products of the end of pregnancy stimulated nonbranching angiogenesis.

Phenotypical characteristics of peripheral blood monocytes in normal pregnancy and gestosis.

Monocyte migration from the peripheral blood to the uterine decidual tissue is essential for the regulation of placental development. We evaluated the phenotypical changes in the peripheral blood monocytes in pregnant women. The peripheral blood counts of monocytes expressing CD11b, CD47, and integrin β7 were elevated in women with normal gestation in comparison with nonpregnant women; the intensity of CD62P, CD11b, CD11c, CD29, CD31, and CD54 expression was higher in pregnancy.

Effects of placental secretory factors on cytokine production by endothelial cells.

We studied the effects of soluble products of the placental tissue from women with normal pregnancy and gestosis on the cytokine secretion by endothelial EA.Hy926 cells. The secretory products of the placental tissue induced the production of angiogenin, bFGF, IL-8, MCP-1, and RANTES by endothelial cells.

Melatonin and pineal gland peptides are able to correct the impairment of reproductive cycles in rats.

Catecholamines play an important role in the hypothalamic regulation of the synthesis and secretion of gonadotropin- releasing hormone, or gonadoliberin. We have shown that melatonin and the pineal gland peptides (epithalamine and epitalon) exert a correcting influence on the diurnal dynamics of norepinephrine (NE) in the medial preoptic area (MPA) and of dopamine (DA) in the median eminence with arcuate nuclei (ME-Arc) disturbed by single administration of the neurotoxic xenobiotic 1,2-dimethylhydrazine (DMH) in female rats. It has been found that experiments with DMH administration can be used as an animal model of female reproductive system premature aging.

In vitro expression of vascular endothelial growth factor and its receptors by placental macrophages.

The expression of VEGF and membrane-bound and soluble forms of the VEGF-R1 receptor in cultured placental macrophages (trimesters I and III of pregnancy) was studied by flow cytometry, cytometric bead array, and ELISA. Nearly all population of placental macrophages (98%) was capable of producing VEGF during the early and late gestational periods. However, the expression of cellular VEGF-R1 varied from 3.

Expression of thrombospondin-1 gene mRNA and protein in the placenta in gestosis.

The expression of TSP-1 gene mRNA and TSP-1 protein in the placental tissue was studied during normal pregnancy and in gestosis. The formation of placental tissue in normal gestation was associated with expression of TSP-1 gene mRNA and of TSP-1 protein. Gestosis was associated with inflammatory reaction in the placenta characterized by increased counts of lymphocytes and macrophages in the villous stroma and involution degenerative changes in tissue.

Regulatory mechanisms for apoptosis in placental tissue during normal pregnancy and gestosis-complicated pregnancy.

The localization of apoptosis and expression of proapoptotic and antiapoptotic factors by the placental tissue were compared during normal pregnancy and gestosis-complicated pregnancy. The degree of apoptosis did not differ in the third trimester of normal pregnancy and gestosis-complicated pregnancy. Increased expression of Fas, caspase-8, and caspase-3 in placental tissue during normal pregnancy was shown to contribute to the suppression of angiogenesis and growth of placental tissue.

Expression of VEGF and VEGF-R3 receptor by placental endothelial cells in health and gestosis.

We carried out a comparative analysis of changes in VEGF secretion and expression of VEGF-R3 receptor by placental endothelial cells in health and gestosis and of changes in VEGF-R3 expression by EA.hy926 human endothelial cells during culturing with supernatants conditioned by placental explants from women with normal pregnancy and patients with gestosis. Reduced secretion of VEGF and expression of VEGF-R3 by placental endothelial cells in gestosis can be caused by functional deficiency of the endothelial cells and low viability of endothelial cells.

Contractile activity of rabbit uterus at the end of pregnancy and a method for its registration.

We developed a method for synchronous registration of electrical activity of the myometrium in pregnant rabbit females and electrocardiograms of the female and fetus on a paper tape and on PC in the online mode using an original pickup for registration of intrauterine pressure in awaken animals in a natural (sitting) posture. The method causes no pregnancy complications and is adequate for evaluation of uterine contractility, female and fetal status in different variants of the experiment.

Comparative efficiency of intraperitoneal interleukine-2 and interferon-A in rats with experimental endometriosis.

Intraperitoneal injection of rat IFN-alpha and human IL-2 to rats with experimental endometriosis led to complete regression of endometrioid heterotopies in 50 and 60% cases, respectively. Retention of the endometrioid epithelium resulted in a significant reduction of proliferative activity of its cells, degree of vascularization, and number of macrophages in the leukocytic infiltration of endometrioid heterotopies.

Spontaneous and LPS-induced secretion of cytokines by villous chorion tissue.

Secretion of IL-1alpha, IL-1beta, IL-6, IL-10, and TNF-alpha cytokines by villous chorion cultures (7-14 weeks) during normal pregnancy and in spontaneous abortions was studied. Secretion of IL-1alpha and IL-6 increased 4.5 and 7.

Study of cytokine profile and angiogenic potential of peritoneal fluid in patients with external genital endometriosis.

The concentrations of proinflammatory cytokines (IL-1beta, IL-6), vascular endothelium growth factor, tumor growth factor-beta, and insulin-like growth factor-1 were measured in the peritoneal fluid of patients with external genital endometriosis and healthy women by enzyme immunoassay. The effect of peritoneal fluid from patients with external genital endometriosis on proliferative activity of EA.Hy926 human endothelial cells was evaluated by the method based on the analysis of cell cycle by flow cytometry.

Local production of interleukins and growth factors in external genital endometriosis.

Secretion of some IL and growth factors (VEGF, IGF-I, TGFbeta) by endometrial tissues and endometrioid heterotopies was studied in vitro in patients with external genital endometriosis of different severity. The production of IL-1beta, IL-2, IL-6, and VEGF in the endometrium increased in severe external genital endometriosis, while the secretion of TGFbeta decreased; hyperproduction of IL-2, IL-6, VEGF and decreased production of TGFbeta were detected in endometrioid foci. Presumably, local cytokine imbalance and increased proliferative activity of endometrial cells are involved in the mechanisms of formation and functioning of endometrioid foci.

[Cytogenetic analysis of human spermatozoa using intracytoplasmic sperm injection into mouse oocytes].

The chromosome complement of human spermatozoa has been analyzed after their intracytoplasmic injection into unfertilized mouse oocytes. A total of 427 metaphase plates have been obtained, including 176 metaphase plates from spermatozoa with normal head morphology (108 and 68 spermatozoa from patients with normal (the control group) and abnormal spermogram parameters, respectively), and 251 metaphase plates from spermatozoa with abnormal heads (76, 91, 67, and 17 spermatozoa with large, amorphous, elongated, and round heads, respectively). The frequency of chromosome abnormalities in the control group is 26.

[Genomic and molecular medicine].

Molecular medicine is a new research field underlain by achievements of the Human Genome Project. The review considers the contribution of the Laboratory of Prenatal Diagnostics of the Ott Institute of Obstetrics and Gynecology to the development of molecular medicine in Russia. Special emphasis is placed on molecular diagnostics, predictive medicine, and gene therapy.

[Analysis of the association of HLA-DQ1 alleles with mutation of the 21-hydroxylase gene in patients with congenital adrenal hyperplasia].

In 96 patients with congenital adrenal hyperplasia (CAH) and 50 healthy donors from northwestern Russia the distribution of the HLA-DQA1 alleles and the mutation spectrum and frequency at the CYP21B gene were examined. In the patients with nonclassical (NC) CAH, the distribution of the HLA-DQA1 polymorphic alleles was similar to that in the population sample. In the patients with the salt-wasting form of the disease a statistically significant decrease of the *0401 or *501 major allele frequency was observed.

[Dependence of the efficacy of transfecting muscle fibers in vivo on electroporation conditions].

This study is a survey of in vivo experiments on transfection of laboratory mouse muscle fibers by electroporation using an original device generating electric impulses. Transfection efficiency proved to depend on DNA dose and the number of electric impulses. It can be increased significantly by electroporation at varying pulse burst polarity.

[Experimental progestogenic activity of novel derivatives of 17alpha-hydroxyprogesterone].

Experiments on infantile female rabbits showed that new 17a-hydroxyprogesterone derivatives (AMOL phenyl propionate, AMOL isopropyl ester) possess a pronounced gestagenic activity. In particular, AMOL isopropyl ester is capable of maintaining pregnancy in ovariectomized animals (Corner-Allen assay).

Hormonal function and proliferative activity of thymic cells in humans: immunocytochemical correlations.

Objectives: The immunocytochemical study of the localization of hormones in thymic cells has been performed to clarify possible correlations of their expression with proliferative activity of thymocytes.

Methods: We used commercial antibodies to serotonin, melatonin, somatostatin, glucagon, gastrin, beta-endorphin and histamine, and ABP or BSP kits for visualization of reaction. Computer image analysis was used to find correlations between hormone production and proliferative activity of thymocytes.

Secretion of proinflammatory cytokines by villous chorion tissue in spontaneous abortion.

Secretion of proinflammatory cytokines IL-1 beta, TNF-alpha, IL-6, IFN-alpha, and IFN-gamma by the chorion tissue (8-12 weeks) was studied in normal gestation and spontaneous abortion. The production of IL-1 beta, TNF-alpha, and IFN-alpha virtually did not change in spontaneous abortion, while IFN-gamma was not secreted in all experimental groups. The production of IL-6 increased more than 2-fold in patients with spontaneous abortion during the first trimester.

[Analysis of the polymorphic alleles of genes encoding phase 1 and phase 2 detoxication enzymes in patients with endometriosis].

Polymorphysms of the three genes encoding phase 1 (CYP1A1, mEPH1, and CYP2E2) and the three genes encoding phase 2 (NAT2, GSTM1, and GSTT1) xenobiotic detoxication enzymes were typed by use of PCR in 74 patients with extragenital endometriosis. Distribution of the CYP1A1, mEPHX1, CYP2E1, NAT2, and GSTM1 polymorphic alleles in the patient group corresponded to that in the control group. At the same time, functionally defective genotypes GSTM1 0/0, NAT2 S/S; GSTM1 0/0, GSTT1 0/0; and GSTT1 0/0, NAT2 S/S were three, four and eight times more frequent among the patients than in healthy individuals.

[The frequency of heteroploidy in spermatozoa of patients with infertility].

The incidence of heteroploid spermatozoa was studied by mono- and dual-colored fluorescence in situ hybridization in semen samples from donors and patients with normal and impaired spermatogenesis. The frequency of heteroploid sperm in the ejaculate was linearly and inversely correlated with sperm parameters (sperm concentration in the ejaculate and proportion of motile and morphologically normal spermatozoa). The level of heterploidy was the most significant in the semen samples from patients with oligoasthenoteratospermia and oligoasthenospermia.

[Molecular genetic analysis of Y-chromosome micro deletions in men with severe spermatogenic defects].

Microdeletions of the Y-chromosomal AZF loci were revealed in 10 (12%) of 82 patients with severe idiopathic spermatogenetic defects. Deletions involved AZFc in six patients, AZFa in one patient, AZFb + c in two patients, and AZFa + b + c in one patient. Microdeletion analysis employed multiplex PCR with 22 pairs of primers directed to Y-specific STS of deletion intervals 5, 6, and 7 (Yq11).