Astrometry and geodesy with radio interferometry: experiments, models, results

Summarizes current status of radio interferometry at radio frequencies between Earth-based receivers, for astrometric and geodetic applications. Emphasizes theoretical models of VLBI observables that are required to extract results at the present accuracy levels of 1 cm and 1 nanoradian. Highlights the achievements of VLBI during the past two decades in reference frames, Earth orientation, atmospheric effects on microwave propagation, and relativity.Comment: 83 pages, 19 Postscript figures. To be published in Rev. Mod. Phys., Vol. 70, Oct. 199

Novel Insights into the Regulatory Role of Nuclear Factor (Erythroid-Derived 2)-Like 2 in Oxidative Stress and Inflammation of Human Fetal Membranes

Fetal membrane dysfunction in response to oxidative stress (OS) is associated with adverse pregnancy outcomes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is one of the regulators of innate OS response. This study evaluated changes in Nrf2 expression and its downstream targets heme oxygenase (HO-1) and peroxisome proliferator-activated receptor gamma (PPARγ) in fetal membranes during OS and infection in vitro. Furthermore, we tested the roles of sulforaphane (SFN; an extract from cruciferous vegetables) and trigonelline (TRN; an aromatic compound in coffee) in regulating Nrf2 and its targets. Fetal membranes (n = 6) collected at term were placed in an organ explant system were treated with water-soluble cigarette smoke extract (CSE), an OS inducer (1:10), and lipopolysaccharide (LPS; 100 ng/mL). Nrf2 expression, expression, its enhancement by sulforaphane (SFN, 10 µM/mL) and down regulation by TRN (10uM/mL) was determined by western blots. Expression of Nrf2 response elements PPARγ (western) heme oxygenase (HO-1), and IL-6 were quantified by ELISA. CSE and LPS treatment of fetal membranes increased nrf2, but reduced HO-1 and PPARγ and increased IL-6. Co-treatment of SFN, but not with TRN, with CSE and LPS increased Nrf2 substantially, as well as increased HO-1 and PPARγ and reduced IL-6 expression. Risk factor-induced Nrf2 increase is insufficient to generate an antioxidant response in fetal membranes. Sulforaphane may enhance innate antioxidant and anti-inflammatory capacity by increasing NRF-2 expression

Does Progesterone Alter Toll-Like Receptor-Stimulated Monocyte Production of Cytokines?

OBJECTIVE: Current models for infection-mediated preterm birth suggest that bacteria stimulate the production of proinflammatory cytokines and cause the fetus to lose its immunological privileges. Pharmacological levels of progesterone (P4) have been proposed to inhibit preterm birth by suppressing such immune reactions that lead to rejection of the fetal allograft. Bacteria stimulate the production of proinflammatory cytokines through interactions with the Toll-Like Receptors (TLRs). We studied whether P4 alters TLR-2 and TLR-4 agonist-stimulated IL-1b and TNF-a production by human monocytes in vitro. STUDY DESIGN: Human monocytes (THP-1 cells) were plated and preincubated overnight. Progesterone was added at increasing doses of 0 to 10 mg/ ml and incubated for 24 h. Cells were then stimulated with 0 to 8 mg/ml Pam3Cys (a TLR-2 agonist), 0 to 10 mg/ml Lipopolysaccharide (LPS, a TLR-4 agonist) or 0 to10 mg/ml Lipid A (a TLR-4 agonist) for an additional 24 h. Concentrations of IL-1b and TNF-a in the conditioned medium were then quantified by ELISA. Each experiment was replicated three times. RESULTS: For monocytes stimulated with 1 mg/ml Pam3Cys, 1 mg/ml LPS, or 1 mg/ml Lipid A, pre-treatment with 10 mg/ml P4 inhibited the production of TNF-a but enhanced the production of IL-1b. Progesterone at this superphysiological concentration also inhibited the dose-dependent rise in TNF-a production but enhanced the dose-dependent rise in IL-1b production caused by each TLR agonist. CONCLUSION: High levels of P4 inhibit the production of TNF-a but increase the production of IL-1b by monocytes stimulated with TLR-2 or TLR-4 agonists. These results suggest that any potential immunomodulatory effects of P4 are similar for TLR-2 and TLR-4 mediated inflammation

Does progesterone inhibit bacteria-stimulated interleukin-8 production by lower genital tract epithelial cells?

Objective: Progesterone (P4) has been clinically shown to prevent the recurrence of preterm birth. The mechanism(s) of action is unclear, but may involve modulation of the immunologic inflammatory response of the lower genital tract. We evaluated the effects of P4 on interleukin-8 (IL-8) production by vaginal and cervical epithelial cells stimulated with bacterial species that are commonly associated with preterm birth. Methods: Vaginal and endocervical epithelial cells were incubated with up to 10,000 ng/mL P4 overnight and stimulated with heat-killed Escherichia coli, Gardnerella vaginalis, or Ureaplasma urealyticum. Concentrations of IL-8 in conditioned medium were quantified by ELISA and viability of the cell cultures was measured by the reduction of a tetrazolium salt. Results: E. coli, G. vaginalis and U. urealyticum-stimulated IL-8 production for both cell lines. P4 inhibited basal and bacteria-stimulated IL-8 production for vaginal epithelial cells but enhanced IL-8 production by endocervical cells. P4 reduced the number of viable cells for both cell lines. Conclusions: P4 inhibits IL-8 production by vaginal epithelial cells stimulated with pathogens associated with preterm birth, possibly by reducing the number of viable cells or by inhibiting their proliferation. Although P4 also reduces proliferation of endocervical cells it also increases their production of IL-8.Peer Reviewe