Ex-vivo mechanical sealing properties and toxicity of a bioadhesive patch as sealing system for fetal membrane iatrogenic defects

Preterm prelabor rupture of membranes (PPROM) is the most frequent complication of fetal surgery. Strategies to seal the membrane defect created by fetoscopy aiming to reduce the occurrence of PPROM have been attempted with little success. The objective of this study was to evaluate the ex-vivo mechanical sealing properties and toxicity of four different bioadhesives integrated in semi-rigid patches for fetal membranes. We performed and ex-vivo study using term human fetal membranes to compare the four integrated patches composed of silicone or silicone-polyurethane combined with dopaminated-hyaluronic acid or hydroxypropyl methylcellulose (HPMC). For mechanical sealing properties, membranes were mounted in a multiaxial inflation device with saline, perforated and sealed with the 4 combinations. We measured bursting pressure and maximum pressure free of leakage (n = 8). For toxicity, an organ culture of membranes sealed with the patches was used to measure pyknotic index (PI) and lactate dehydrogenase (LDH) concentration (n = 5). All bioadhesives achieved appropriate bursting pressures, but only HPMC forms achieved high maximum pressures free of leakage. Concerning toxicity, bioadhesives showed low PI and LDH levels, suggesting no cell toxicity. We conclude that a semi-rigid patch coated with HPMC achieved ex-vivo sealing of iatrogenic defects in fetal membranes with no signs of cell toxicity. These results warrant further research addressing long-term adhesiveness and feasibility as a sealing system for fetoscopy

Intraamniotic sealing of fetoscopic membrane defects in ex vivo and in vivo sheep models using an integrated semirigid bioadhesive patch

BACKGROUND: Preterm prelabor rupture of membranes is the most frequent complication of fetoscopic surgery. Strategies to seal the membrane defect created by fetoscopy have been attempted with little success. We previously developed an integrated semirigid bioadhesive patch composed of silicone and hydroxypropyl methylcellulose that achieved ex vivo sealing of membrane defects. OBJECTIVE: To evaluate the feasibility of the insertion of our integrated semirigid bioadhesive patches using a fetoscopic technique and to test the adhesion in ex vivo human membranes and in an in vivo ovine model. STUDY DESIGN: An experimental study involving 2 experiments: (1) ex vivo—human fetal membranes were mounted in a custom-designed model with saline solution simulating intraamniotic pressure. The insertion of 2 different bioadhesive patches made of silicone-hydroxypropyl methylcellulose and silicone-polyurethane-hydroxypropyl methylcellulose was performed through a 12-Fr cannula mimicking fetoscopic surgery technique. The experiment was repeated 10 times with membranes from different donors. Measures included insertion time, successful insertion, and adhesion at 5 minutes; (2) in vivo—16 patches of silicone-hydroxypropyl methylcellulose were inserted by fetoscopy in the amniotic cavity of pregnant sheep (4 bioadhesives per animal, in 4 ewes). Measures included successful insertion, adhesion at 5 minutes, and adhesion at the end of surgery. RESULTS: In the ex vivo insertion study, there was no difference in the insertion time between silicone-hydroxypropyl methylcellulose and silicone-polyurethane-hydroxypropyl methylcellulose patches (P=.49). Insertion was successful in all cases, but complete adhesion at 5 minutes was superior for silicone-hydroxypropyl methylcellulose (P=.02). In the in vivo study, insertion of silicone-hydroxypropyl methylcellulose by fetoscopy was feasible and successful in all cases, and no complications were reported. Adhesion persisted at 5 minutes and at the end of the surgery in 68.8% and 56.3% of the patches, respectively. CONCLUSION: We describe the feasibility of deploying through a fetoscopic trocar a semirigid silicone-hydroxypropyl methylcellulose patch that seals fetal membranes after an invasive fetal procedure. The results warrant further research for improving long-term adhesion and developing a clinically applicable system.This project has been funded by the Cellex Foundation and the Erasmus+ Programme of the European Union (Framework Agreement number: 2013-0040). This publication reflects only the authors’ views, and the Commission cannot be held responsible for any use that may be made of the information contained therein. T.M. was supported by a predoctoral grant from Erasmus Mundus FetalMed-PhD. E.E. has received funding from the Departament de Salut under grant number SLT008/18/00156.Peer ReviewedPostprint (published version

The Importance of IgG Avidity and the Polymerase Chain Reaction in Treating Toxoplasmosis during Pregnancy: Current Knowledge

A brief report on the nature and epidemiology of T. gondii infection is firstly presented. The importance of the specific IgG avidity test and polymerase chain reaction (PCR) for toxoplasmosis is discussed, along with their significance and importance as auxiliary methods for determining the most likely time for the initial infection by this coccidian and for defining the therapeutic strategy. Lastly, practical comments are made in relation to the classical therapeutic regimens, with special attention to the indications for fetal treatment, when this is necessary

Craniosynostosis: prenatal diagnosis by 2D/3D ultrasound, magnetic resonance imaging and computed tomography

Craniosynostosis is defined as the process of premature fusion of one or more of the cranial sutures. It is a common condition that occurs in about 1 to 2,000 live births. Craniosynostosis may be classified in primary or secondary. It is also classified as nonsyndromic or syndromic. According to suture commitment, craniosynostosis may affect a single suture or multiple sutures. There is a wide range of syndromes involving craniosynostosis and the most common are Apert, Pffeifer, Crouzon, Shaethre-Chotzen and Muenke syndromes. The underlying etiology of nonsyndromic craniosynostosis is unknown. Mutations in the fibroblast growth factor (FGF) signalling pathway play a crucial role in the etiology of craniosynostosis syndromes. Prenatal ultrasound's detection rate of craniosynostosis is low. Nowadays, different methods can be applied for prenatal diagnosis of craniosynostosis, such as two-dimensional (2D) and three-dimensional (3D) ultrasound, magnetic resonance imaging (MRI), computed tomography (CT) scan and, finally, molecular diagnosis. The presence of craniosynostosis may affect the birthing process. Fetuses with craniosynostosis also have higher rates of perinatal complications. In order to avoid the risks of untreated craniosynostosis, children are usually treated surgically soon after postnatal diagnosis.Univ Fed Sao Paulo, Paulista Sch Med, Dept Obstet, Sao Paulo, SP, BrazilAUSL Reggio Emilia, Guastalla Civil Hosp, Dept Obstet & Gynecol, Reggio Emilia, RE, ItalyUniv Fed Sao Paulo, Paulista Sch Med, Dept Obstet, Sao Paulo, SP, BrazilWeb of Scienc

Metabolomic profiling and assessment of antimicrobial, antioxidant and genotoxic potential of Unonopsis guatterioides R.E.Fr. (Annonaceae) fruits

Unonopsis guatterioides (A.DC.) R.E.Fr., is found mainly in the Pantanal, Cerrado and Amazon biomes and, some species of this genus are used in folk medicine. The analysis by HPLC-ESI-MS revealed the presence of alkaloids previously reported for Unonopsis genus, such as asimilobine, anonaine, nornuciferine, glaucine and norglaucine. In contrast, the heliamine, norjuziphine and anomuricine alkaloids are being reported for the first time in the Unonopsis genus, while this is the first report of azafluoranthene alkaloid triclisine in the Annonaceae family. These results showed the promising application of mass spectrometric monitoring of complex extracts in the search for novel natural products for the food, pharmaceutical, and cosmetic industries, thus simplifying phytochemical analysis. Bioactive analysis based on antioxidant activity indicated that ethanolic extracts of the peels and pulps of the fruits from U. guatterioides showed low scavenging activity against the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), with IC50 values > 100 μg*mL−1, using as reference the ascorbic acid (IC50 < 50 μg*mL−1). These results are in concordance with the chemical profiles, whose major compounds proved to be O-substituted phenolic derivatives. Furthermore, ethanolic extracts of the peels (UGP-1) and pulps (UGP-2) of the fruits from U. guatterioides showed weak activity against Staphylococcus pseudintermedius, S. aureus and S. epidermidis, with MIC values above 1000 μg*mL−1. The combination of the ethanolic extract of the pulps of fruits from U. guatterioides and ampicillin resulted in an additive effect (FICI = 1.0), when tested against S. aureus and a strain of S. epidermidis. These results suggest that the pulps' ethanolic extract, when combined with the antibiotic ampicillin, can strengthen the therapy for S. aureus and S. epidermidis infection. Additionally, no genotoxic activity of the ethanolic extracts of fruits from U. guatterioides (UGP-1 and UGP-2) was detected at the tested concentrations (0.25, 1.25, 2.5 and 5.0 mg*mL−1). The genotoxic property was performed using the Somatic Mutation and Recombination assay (SMART Test), in vivo, in somatic cells of Drosophila melanogaster