Coordinated expression of TNFα- and VEGF-mediated signaling components by placental macrophages in early and late pregnancy.

INTRODUCTION: Mononuclear phagocytes are thought to significantly contribute to cytokine regulation at the maternal-foetal interface, but the role of placental macrophages has been poorly investigated. TNFα and VEGF were demonstrated to have regulatory effects on basic structures of the placenta, particularly the trophoblast and blood vessels. The aims of this study were to determine the expression of TNFα, VEGF and related receptors in placental macrophages, and how does the participation of placental macrophages alter with gestational age in TNFα- and VEGF-mediated signaling. METHODS: Macrophages were isolated from placental villous tissue from normal pregnancies at either 9-12 or 38-40 weeks gestation. Cell surface receptors (TNFR1, TNFR2, VEGFR1, and VEGFR2) and intracellular TNFα and VEGF were quantified by flow cytometry after antibody staining. Basal and stimulated secretion of both cytokines and soluble TNF receptors was quantified by cytometric bead arrays. Secreted VEGFR1 was measured by ELISA. RESULTS: The expression of TNFR1 and VEGFR1 was remarkably variable and did not change from first to third trimester. There was minimal basal TNFα production in the placental macrophages, but nearly all cells in the population produced VEGF. TNFα and VEGF secretion increased with gestational age accompanied by decreased secretion of the antagonists sTNFR1 and sVEGFR. Macrophages isolated from early term placentas were less effective in responding to bacterial endotoxin. Lipopolysaccharide induced increases in the secretion of TNFα, TNFR1, TNFR2, and VEGFR1 but did not affect the production of VEGF. In late pregnancy, a significant correlation was observed between TNFR1 and VEGFR1. DISCUSSION: The progression of pregnancy is accompanied by the concerted increase in TNFα and VEGF secretion and decrease in the production of their soluble receptors, but the expression of cell surface receptors does not depend on gestational age. The observed patterns of basal and stimulated expression of TNFα and VEGF may reflect the dual immune and morphogenetic roles of placental macrophages in gestation. Compatible patterns of TNFR1 and VEGFR1 expression suggest common regulatory pathways for these receptors.

[Evaluation of the placental morphofunctional state in perinatal HIV transmission].

The paper presents the results of investigating the mechanisms of placental insufficiency and transplacental infection of infants born to HIV-infected mothers who have received specific antiretroviral therapy mothers and who have not.

[Algorithm of examination and treatment of women with mixed urine incontinence].

The examination including filling cystometry, urethral profilometry, uroflowmetry, perineal ultrasonography was made in 62 females aged from 29 to 66 years with a clinical diagnosis of mixed urine incontinence (MUI). Irrespective of the verified diagnosis, the treatment started with conservative methods. Surgical intervention was performed if moderate and severe MUI persisted after conservative therapy. The diagnosis of MUI was confirmed in 66.1% examinees. Stress urine incontinence and hyperactive urinary bladder were diagnosed in 9.7 and 24.2% cases, respectively. The conservative treatment resulted in disappearance of the symptoms of MUI in 43.9%, in partial response in 34.1% patients. 22% patients were treated surgically. Urodynamic and ultrasonic indices helping choice of surgical policy in MUI were not determined. Thus, the principle of staged and comparative assessment of clinical, urodynamic and ultrasound findings improves diagnosis of MUI. Pathogenetic conservative treatment, as the first stage of MUI therapy, provides indications for surgery.

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.

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. The concentrations of IL-1beta, IL-6, and insulin-like growth factor-1 were increased in patients with endometriosis in comparison with healthy women. The peritoneal fluid from patients with endometriosis (but not from healthy women) significantly increased mitotic activity of endothelial cells and exhibited high angiogenic potential, which can promote implantation and growth of endometrial transplants. Presumably, insulin-like growth factor-1 stimulates this process.