Cervical ripening after cesarean section: a prospective dual center study comparing a mechanical osmotic dilator vs. prostaglandin E2.

OBJECTIVES: Worldwide, the overall cesarean section is rising. Trial of labor after cesarean (TOLAC) is an overall safe option with an immediate impact on neonatal and maternal short- and long-term health. Since the use of prostaglandins in cervical ripening is associated with an increased risk of uterine rupture, mechanical methods as balloon catheters or osmotic dilators have been suggested for cervical ripening prior to induction of labour. Here we are analyzing and comparing the VBAC rate, as well as maternal and fetal outcome in cervical ripening prior to TOLAC. METHODS: This prospective dual center study analyses maternal and neonatal outcomes of TOLAC in women with an unfavorable cervix requiring cervical ripening agent. The prospective application of an osmotic dilator (Dilapan-S, n=104) was analysed in comparison to the retrospective application of off-label dinoprostone (n=102). RESULTS: The overall fetal and neonatal outcome revealed no significant differences in both groups. Patients receiving cervical ripening with the osmotic dilator delivered vaginally/by ventouse in 52% of cases, compared to 53% when using dinoprostone (p=0.603). The interval between application to onset of labor was significantly higher in the osmotic dilator group (37.9 vs.20.7 h, p=<0.001). However, time from onset of labor to delivery was similar in both groups (7.93 vs. 7.44 h, p=0.758). There was one case of uterine rupture in the dinoprostone group. CONCLUSIONS: Our data shows that the application of the osmotic dilator leads to similar outcomes in VBAC rate and time from onset of labor to delivery as well as safety in both groups compared to off-label use dinoprostone. Cervical ripening using the mechanical dilator is a viable and effective option, without the risk of uterine hyperstimulation.

Effects of IGFBP-1 and IGFBP-2 and their fragments on migration and IGF-induced proliferation of human dermal fibroblasts.

OBJECTIVE: A family of six insulin-like growth factor (IGF) binding-proteins (IGFBP) bind to IGF-I and IGF-II with high affinity and modulate their activity. We have recently shown that a neutrophil-derived protease activity cleaved IGFBP-1, -2 and -4. IGFBP-1 and IGFBP-2 have a C-terminal Arg-Gly-Asp (RGD) sequence, and IGFBP-1 has been shown by others to stimulate migration through binding of its RGD sequence to α5ß1 integrin. The aim of this study was to determine the effect of this IGFBP protease on IGF-induced proliferation and the effect of IGFBP-1 and IGFBP-2 and their proteolytic fragments on migration in normal and high glucose of human dermal fibroblasts (HDF). DESIGN: We investigated the effect of intact or cleaved IGFBP-1 and -2 on proliferation in cultured HDFs and on HDF migration in normal and high glucose. RESULTS: Both IGFBP-1 and IGFBP-2 and their proteolytic fragments stimulated HDF migration and the stimulatory effect was abolished by pre-treating cells with a α5ß1 integrin antibody. High glucose impaired migration of HDFs; however, the addition of IGFBP-1, IGFBP-2 or fragments increased migration to levels observed in normoglycemia. IGFBP-2 inhibited IGF-II induced proliferation; however, the inhibitory effect was reduced after being cleaved. Intact native IGFBP-1 showed either potentiating or inhibitory effects on IGF-I induced proliferation depending on the confluence of cells, and proteolysis of IGFBP-1 did not change these effects. IGFBP-1 was found to increase phosphorylation of FAK and ERK1/2 and this effect was inhibited by the monoclonal integrin a5ß1 ab. CONCLUSIONS: IGFBP-1 and -2 and their proteolytic fragments may improve tissue repair under inflammatory conditions, through effects on proliferation and migration of HDFs in normal and high glucose.

Neutrophil-derived azurocidin cleaves insulin-like growth factor-binding protein-1, -2 and -4.

OBJECTIVE: Azurocidin is an important inflammatory mediator and considered to be an inactive serine protease homologue. It has previously been reported that azurocidin is a possible IGFBP-1 specific protease; however, the protease-activity of azurocidin was not isolated in its active form. The aim of this study was to determine the effect of neutrophil-derived azurocidin on the six different IGFBPs, focusing especially on IGFBP-1. METHODS: IGFBPs were incubated with azurocidin in phosphate-buffered saline for 2 h and proteolysis was studied by SDS-PAGE. Analysis of azurocidin was performed by MALDI-TOF peptide mass fingerprint and MALDI-TOF/TOF peptide sequencing. RESULTS: The neutrophil-derived preparation of azurocidin cleaved IGFBP-1, IGFBP-2 and IGFBP-4. IGFBP-1 bound to IGF-I was also degraded whereas IGF-II was shown to have an inhibitory effect on proteolysis of IGFBP-1. The proteolytically active preparation of neutrophil-derived azurocidin was found to be glycosylated and determined to be 31 kDa by SDS-PAGE. CONCLUSIONS: Our results indicate that the neutrophil-derived preparation of azurocidin contains a protease activity which cleaves IGFBP-1, IGFBP-2 and IGFBP-4. These findings are of interest since both IGFBP-1 and azurocidin increase during inflammation. The effect of azurocidin on IGFBP- and IGF-activity needs to be further investigated.

Chemoselective catalytic hydrogenation of acrolein on Ag(111): effect of molecular orientation on reaction selectivity.

The adsorption and hydrogenation of acrolein on the Ag(111) surface has been investigated by high resolution synchrotron XPS, NEXAFS, and temperature programmed reaction. The molecule adsorbs intact at all coverages and its adsorption geometry is critically important in determining chemoselectivity toward the formation of allyl alcohol, the desired but thermodynamically disfavored product. In the absence of hydrogen adatoms (H(a)), acrolein lies almost parallel to the metal surface; high coverages force the C=C bond to tilt markedly, likely rendering it less vulnerable toward reaction with hydrogen adatoms. Reaction with coadsorbed H(a) yields allyl alcohol, propionaldehyde, and propanol, consistent with the behavior of practical dispersed Ag catalysts operated at atmospheric pressure: formation of all three hydrogenation products is surface reaction rate limited. Overall chemoselectivity is strongly influenced by secondary reactions of allyl alcohol. At low H(a) coverages, the C=C bond in the newly formed allyl alcohol molecule is strongly tilted with respect to the surface, rendering it immune to attack by H(a) and leading to desorption of the unsaturated alcohol. In contrast with this, at high H(a) coverages, the C=C bond in allyl alcohol lies almost parallel to the surface, undergoes hydrogenation by H(a), and the saturated alcohol (propanol) desorbs.

IGFBP-1 protease activity and IGFBP-1 fragments in a patient with multiple myeloma.

OBJECTIVE: Cleavage of IGFBPs by proteases results in IGFBP fragments that have altered IGF-binding affinity, and IGF-independent roles. We have previously purified a specific IGFBP-1 protease activity from the urine of an individual with multiple myeloma and dermatitis. The aim of this study was to determine whether IGFBP-1 protease activity and/or IGFBP-1 fragments were present in the circulation of this patient. METHODS: The size of immunoreactive IGFBP-1 in serum samples was determined after Superose 12 chromatography. Intact IGFBP-1 and IGFBP-1 fragments were characterized in four RIAs and after SDS-PAGE. RESULTS: Specific proteolysis of IGFBP-1 generated an N-terminal fragment (IGFBP-1(1-130)) with a predicted molecular mass of 13kDa but an apparent mass of 21kDa on SDS-PAGE. A C-terminal fragment (IGFBP-1(131-234)) produced in vitro migrated at 11.4kDa, close to its predicted size. However a C-terminal fragment of cleaved IGFBP-1 (IGFBP-1(142-234)) migrated at 14kDa on SDS-PAGE. Serum from the patient inhibited IGFBP-1 protease activity. Immunoreactive IGFBP-1 in patient serum was present at molecular masses consistent with IGFBP-1 fragments, in addition to intact IGFBP-1. CONCLUSIONS: Specific cleavage of IGFBP-1 occurs at the tissue level and not in the circulation in a patient with multiple myeloma and dermatitis. The fragments that are generated may have endocrine roles.