Inhibition of the iron-mediated generation of toxic oxygen species by polymorphonuclear leukocytes (PMN) might prevent oxidative damage and thus enhance phagocytic function of PMN. To investigate this point, we studied the effect of the specific iron chelator, deferoxamine, on the antibacterial function of PMN. PMN were incubated for 20 hr with various concentrations of deferoxamine at 37 degrees C in medium containing 0.54 microM endogenous iron. The cells were then washed, and the phagocytic cell function was assessed. The results were compared with those for control PMN preincubated for 20 hr without deferoxamine, and those of nonincubated PMN. Compared with that of control PMN, the uptake of radiolabeled Staphylococcus aureus by PMN treated with 1 microM-1 mM deferoxamine was, on average, 10%-20% higher. This effect was not observed when iron-saturated deferoxamine (DFO) was used. Bacterial uptake was similarly increased in nonpreincubated PMN or PMN preincubated for 20 hr at 4 degrees C instead of 37 degrees C. The intracellular killing capacity of both deferoxamine-treated and control PMN exceeded 90%. PMN incubated for 20 hr at 37 degrees C with DFO not only phagocytosed more bacteria than control cells, but were also capable of killing the greater number of bacteria ingested. This increased activity of deferoxamine-treated PMN was accompanied by enhanced generation of chemiluminescence and production of superoxide during phagocytosis of S. aureus. These findings indicate that deferoxamine may enhance the antibacterial activity of PMN by protecting the cells against damage by iron-mediated generation of toxic oxygen metabolites in resting PMN.

No abstract

Absorption of iron was studied with a double-isotope technique that allowed differentiation between “mucosal uptake,” “mucosal transfer,” and ultimate “retention” of iron. A physiologic dose of ferrous sulfate was administered to 25 healthy young adults, 40 active aged persons, and 20 patients with uncomplicated iron deficiency. Radioactivity was measured with a whole-body scanner. Iron absorption values were not decreased in aged subjects compared to young adults. Mucosal uptake, mucosal transfer, and retention of iron were equally increased in both young and old patients with iron deficiency. In 12 young adults and 33 aged persons red cell iron uptake was studied in addition to iron absorption. Young adults utilized 91% of the retained, orally administered iron and the aged only 66%. An increase in ineffective erythropoiesis in old age is suggested.

The effect of pretransfusion incubation of platelets at 37 degrees C was assessed because of the controversial reports about its relevance. A dual-label technique (111indium and 114mindium) was applied in 10 healthy subjects receiving warmed and unwarmed autologous platelets simultaneously. Fresh platelet concentrates were infused into five subjects, whereas the other five subjects received stored platelet concentrates. The mean platelet volume decreased in all platelet concentrates during incubation, reflecting the restoration of the discoid shape of the platelets. The mean decrease was 0.35 fL (P = .003). However, the initial recovery and the mean platelet life-span were not improved by this procedure. It was concluded that there is no evidence that brief warming of platelets has any beneficial effect on platelet viability in healthy volunteers.

No abstract

Inhibition of the iron-mediated generation of toxic oxygen species by polymorphonuclear leukocytes (PMN) might prevent oxidative damage and thus enhance phagocytic function of PMN. To investigate this point, we studied the effect of the specific iron chelator, deferoxamine, on the antibacterial function of PMN. PMN were incubated for 20 hr with various concentrations of deferoxamine at 37 degrees C in medium containing 0.54 microM endogenous iron. The cells were then washed, and the phagocytic cell function was assessed. The results were compared with those for control PMN preincubated for 20 hr without deferoxamine, and those of nonincubated PMN. Compared with that of control PMN, the uptake of radiolabeled Staphylococcus aureus by PMN treated with 1 microM-1 mM deferoxamine was, on average, 10%-20% higher. This effect was not observed when iron-saturated deferoxamine (DFO) was used. Bacterial uptake was similarly increased in nonpreincubated PMN or PMN preincubated for 20 hr at 4 degrees C instead of 37 degrees C. The intracellular killing capacity of both deferoxamine-treated and control PMN exceeded 90%. PMN incubated for 20 hr at 37 degrees C with DFO not only phagocytosed more bacteria than control cells, but were also capable of killing the greater number of bacteria ingested. This increased activity of deferoxamine-treated PMN was accompanied by enhanced generation of chemiluminescence and production of superoxide during phagocytosis of S. aureus. These findings indicate that deferoxamine may enhance the antibacterial activity of PMN by protecting the cells against damage by iron-mediated generation of toxic oxygen metabolites in resting PMN.

Our fax numbers: 617-739-9864 and 617-734-4457Our e-mail address: letters@nejm.orgWe cannot acknowledge receipt of your letter, but we will notify you when we have made a decision about publication. We are unable to provide prepublication proofs. Please enclose a stamped, self-addressed envelope if you want unpublished material returned to you. Financial associations or other possible conflicts of interest must be disclosed. Submission of a letter constitutes permission for the Massachusetts Medical Society, its licensees, and its assignees to use it in the Journal' s various editions (print, data base, and optical disk) and in anthologies, revisions, and any other form or medium. Correspondence Lorazepam for the Prevention of Recurrent Seizures Related to Alcohol 1. D'Onofrio G, Rathlev NK, Ulrich AS, Fish SS, Freedland ES. Lorazepam for the prevention of recurrent seizures related to alcohol. N Engl J Med 1999;340:915-9. 2. Miller WC Jr, McCurdy L. A double-blind comparison of the efficacy and safety of lorazepam and diazepam in the treatment of acute alcohol withdrawal syndrome. Clin Ther 1984;6:364-71. 3. O'Brien JE, Meyer RE, Thoms DC. Double-blind comparison of lorazepam and diazepam in the treatment of acute alcohol abstinence syndrome. Curr Ther Res 1983;34:825-31.

No abstract