Redox-sensitive, PEG-shielded carboxymethyl PEI nanogels silencing MicroRNA-21, sensitizes resistant ovarian cancer cells to cisplatin.

A series of branched polyethylenimine (PEI) modifications including PEGylation (PEG2k-PEI) for steric shielding, redox-sensitive crosslinking for synthesis PEG2k-PEI-ss nanogels and subsequent carboxymethylation (PEG2k-CMPEI-ss) for modulation of the polymer pka have been introduced for cellular delivery of Anti-miR-21. The synthesis was characterized using 1H NMR, FTIR, TNBS, potentiometric titration, particle size and ζ potential. Loading of Anti-miR-21 at various N/P ratios was investigated by gel retardation, ethidium bromide dye exclusion, heparin sulfate competition and DNase I digestion experiments. The miR-21 silencing was measured by stem-loop RT PCR in A2780 ovarian cancer cell lines whether it is sensitive to resistant to cisplatin. It has been shown that PEG2k-CMPEI-ss was well suited for delivery of Anti-miR-21 in terms of nucleic acid loading, preservation against extracellular matrix and nucleases and sequence-specific silencing of miRNA-21 in vitro. Moreover, it has been demonstrated that pre-treating cells with Anti-miR-21 loaded nanogels can sensitize them to cis-Pt even at non-toxic concentraions. The results indicate that PEG2k-CMPEI-ss mediated microRNA delivery can be considered as a novel strategy for ovarian cancer therapy.

Late results of endorectal flap in management of high type perianal fistula.

BACKGROUND: Fistula-in-ano is a problematic perianal disease for physicians and patients because of its occasional difficulty in management. Due to the different types of fistulas seen in patients, careful approach is necessary to correctly choose from among the various surgical techniques. One surgical method for complex fistula is the endorectal advancement flap which has been frequently performed because of its low complication rate. METHODS: This study enrolled 40 (33 males, 7 females) patients who suffered from high type fistula (greater than 30%-50% involvement of the external sphincter) as noted on digital rectal examination and endoanalsonography. Patients were seen at Shahid Faghihi Hospital, affiliated with Shiraz University of Medical Sciences, between 2007 and 2011. All enrolled patients received similar preoperational preparation. We used the jackknife operative position and determined the internal orifice of the fistula by inserting a probe, with injection of methylene blue or oxygen peroxide. Endorectal advancement flap included the mucosa, submucosa and thin portion of the muscle that completely covered the sutured internal orifice area. The external orifice was opened to adjust the external border of the external sphincter to allow for effective drainage. RESULTS: All enrolled patients were followed for 36 months, which was noticeable statistically when compared with other study findings of high type fistula. The location of the external orifice, age, sex and bowel habits were not related to recurrence rate. CONCLUSION: Endorectal advancement flap in selected patients who suffer from high type fistula seems to have beneficial effects with a low recurrence rate. Therefore, management of complex high type fistulas remains a challenging topic.