Following a systematic search of desferrithiocin analogs, a polyether derivative, deferitazole (formerly FBS0701), has entered into phase 1 and 2 clinical trials with promising biological properties. However, until now, detailed physicochemical properties of this chelator have not been reported. The compound displays a high affinity and selectivity for iron(III) as demonstrated by the log β2 = 33.39 ± 0.03 and the pFe(3+) value of 22.3. Two equilibrating isomeric forms of the iron(III) complex exist under biological conditions. Deferitazole also binds the trivalent metals Al(III) and La(III) with high affinity; log β2 values, 26.68 and 21.55 respectively. The affinity of deferitazole for divalent cations is somewhat lower, with the exception of Cu(II) which possesses a log β2 value of 25.5; deferitazole scavenges iron from labile sources such as citrate and albumin with efficiencies comparable with those of other therapeutic iron chelators, including deferasirox, deferiprone and desferrioxamine. The Fe(III)(deferitazole)2 is stable under physiological conditions and does not redox cycle. The high affinity of deferitazole for iron(III) renders it unlikely that this chelator will lead to the redistribution of iron and consequently deferitazole shows considerable promise as a therapeutic iron(III) chelator.
and PDS sutures for closure. Reaction to suture material, however extreme, would be expected to occur in the immediate vicinity of the sutures, rather than cause the widespread changes seen in this case. The second laparotomy did not reveal any evidence of leakage or sepsis that could have caused such a diffuse reaction. The dense ®brotic reaction, containing foreign-body-type giant cell granulomata, was¯orid and universal affecting the whole serosal surface of the small bowel.Concerned that these remarkable ®ndings might represent an idiosyncratic response to Sepra®lm and Sepracoat, the operating surgeon ®led an adverse incident report with the Medical Devices Agency. Four similar cases of foreign-body-type granulomatous reaction following the use of a hyaluronate barrier had been reported to agencies in the USA and the UK. Three involved placement of the barrier following adhesiolysis, and the fourth occurred after repair of a paraduodenal hernia. All patients required subsequent surgery within 6±13 days for small-bowel obstruction, two undergoing extensive small-bowel resection. These ®ve cases in total since marketing approval would represent an occurrence of less than 0.1% for Sepra®lm and 0.01% for Sepracoat. REFERENCES 1 Becker JM, Dayton MT, Fazio VW, et al. Prevention of post operative abdominal adhesions by a sodium hyaluronate based bioresorbable membrane: a prospective randomised double blind multicentre study. J Am Coll Surg 1966;183:297±306 2 Burns JW, Colt MJ, Burgees LS, Skinner KC. Pre-clinical evaluation of Sepra®lm bioresorbable membrane. Eur J Surg 1997;577(Suppl.):40±8 3 Diamond MP. Reduction of post surgical adhesions by intraoperative pre coating with Sepracoat 2 (HAL-C) solution: a prospective randomised, blinded, placebo controlled multicentre study.
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