Effect of Adenoviral-Mediated Transfer of Transforming Growth Factor-β1 on Colonic Anastomotic Healing

Abstract

Gene transfer into the healing colonic anastomosis can be effectively achieved via intraluminal administration of adenoviral vectors. Transfer of transforming growth factor-beta1 increased the strength of colonic anastomoses when given at Day 3 but not at Day 0, demonstrating its diverse effects in the wound healing sequence. Thus, gene transfer of transforming growth factor-beta1 may avoid the need for a diverting stoma in cases of rectal surgery and impaired healing resulting from chemotherapy or radiation.

Stable Gastric Pentadecapeptide BPC 157 in Trials for Inflammatory Bowel Disease (PL-10, PLD-116, PL14736, Pliva, Croatia) Heals Ileoileal Anastomosis in the Rat

“…In contrast to the effects of pentadecapeptide BPC 157, 6,7,[10][11][12][13][14][15][16][17]25,26 other agents' effects appear to have many pitfalls: skin wound healing not accompanied with intestinal anastomosis healing, 40,41 intestinal anastomosis impaired with adhesion-preventing effect, 1 the collagen deposition of anastomoses without the anastomotic strength (IGF-I treatment), 42 or peptides (i.e., EGF, FGF, CSF, TGF-beta, CGRP, GH) needing local, subserosal application into the perianastomotic area, 43,44 and special application system [45][46] as well as carrier. 47 Clearly, huge stability, i.e., stable in human gastric juice more than 24 h, 18 and use without carrier 6,7,[10][11][12][13][14][15][16][17]25,26 (otherwise, peptide+carrier(s)−complex bears considerable methodological/activity dilemmas), 19,20 prominent Fig.…”

Adenoviral Gene Transfer of Active Human Transforming Growth Factor-β2 Elevates Intraocular Pressure and Reduces Outflow Facility in Rodent Eyes

“…36 Our first attempt at adenoviral overexpression of wild-type, latent TGF␤2 in rat eyes resulted in no IOP change, suggesting little in situ activation. Based on bioactivating mutations introduced into the LAP-binding portion of the orthologous monkey TGF␤1, 37 pig TGF␤1, 38 human TGF␤1, 39 cow TGF␤1, 40 rat TGF␤1, 41 mouse TGF␤1, 42 and mouse TGF␤2, 42 we introduced similar mutations into human TGF␤2 to generate spontaneously active human TGF␤2 (Fig. 1).…”

The Effect of an Angiotensin Converting Enzyme Inhibitor on Intestinal Wound Healing

“…This effect was AT1 receptor mediated, because AT1 receptor antagonists valsartan, candesartan, and losartan inhibited AII-induced endoglin expression, whereas the AT2 receptor antagonist PD123319 had no effect [24]. It was also showed that gene transfer of TGF-␤1 increased strength of colonic anastomosis by Migaly et al [25]. Chegini et al reported that TGF-␤ is differentially expressed in serosal tissue of peritoneal organs and adhesions, with higher expression in adhesions and serum of subjects who had developed peritoneal scars [26].…”