Conjugation to the Cell-Penetrating Peptide TAT Potentiates the Photodynamic Effect of Carboxytetramethylrhodamine

Cell-penetrating peptides (CPPs) can transport macromolecular cargos into live cells. However, the cellular delivery efficiency of these reagents is often suboptimal because CPP-cargo conjugates typically remain trapped inside endosomes. Interestingly, irradiation of fluorescently labeled CPPs with light increases the release of the peptide and its cargos into the cytosol. However, the mechanism of this phenomenon is not clear. Here we investigate the molecular basis of the photo-induced endosomolytic activity of the prototypical CPPs TAT labeled to the fluorophore 5(6)-carboxytetramethylrhodamine (TMR).We report that TMR-TAT acts as a photosensitizer that can destroy membranes. TMR-TAT escapes from endosomes after exposure to moderate light doses. However, this is also accompanied by loss of plasma membrane integrity, membrane blebbing, and cell-death. In addition, the peptide causes the destruction of cells when applied extracellularly and also triggers the photohemolysis of red blood cells. These photolytic and photocytotoxic effects were inhibited by hydrophobic singlet oxygen quenchers but not by hydrophilic quenchers.Together, these results suggest that TAT can convert an innocuous fluorophore such as TMR into a potent photolytic agent. This effect involves the targeting of the fluorophore to cellular membranes and the production of singlet oxygen within the hydrophobic environment of the membranes. Our findings may be relevant for the design of reagents with photo-induced endosomolytic activity. The photocytotoxicity exhibited by TMR-TAT also suggests that CPP-chromophore conjugates could aid the development of novel Photodynamic Therapy agents

Synechia after uterine compression sutures

We present a study of 37 women who underwent uterine compression suture for postpartum hemorrhage, with 13 postoperative assessments by hysteroscopy. Synechia occurred in seven patients, of whom three had Asherman syndrome (23% of women who desired pregnancy and had hysteroscopic evaluation) that could not be corrected. 2011 American Society for Reproductive Medicine, Published by Elsevier Inc

Lésions périnéales sév\u27res liées á une extraction foetale par spatules. Quels facteurs de risques ?

Objective To assess risk factors for anal sphincter injury during operative vaginal delivery using spatulas. Patients and methods A monocentric retrospective study of all assisted vaginal deliveries using Thierry and Teissier\u27s spatulas between January 1st, 2008 and December 31st, 2009 in a teaching level III maternity. We studied risk factors such as primiparity, gestational age, maternal age, previous perineal laceration, level and type of presentation, type of expulsion, unsuccessful extraction and successive use of tools, episiotomy, type of anaesthesia and birth weight. Results There were 346 perineal tears (60.5%); among them, 175 (31%) were type 1, 131 (23%) type 2, 35 (6.1%) type 3 and five (0.9%) type 4. There were 235 episiotomy (41.1%). There was no statistically significant difference between all the supposed risk factors and the severe perineal tears. Conclusion There are no relationship between third and fourth degree perineal lesions during spatula\u27s delivery and supposed risk factors of anal sphincter injury. Only statistical tendances between first vaginal delivery and anal sphincter injury and between occipitosacral delivery and anal sphincter injury were found. We need further randomized studies comparing assisted births using spatulas, forceps and vacuum extractors to better assess perineal tears risk factors