Reactions of VX, GB, GD, and HD with nanosize Al(2)O(3). Formation of aluminophosphonates.

Room-temperature reactions of VX, GB, GD, and HD with nanosize Al(2)O(3) (AP-Al(2)O(3)) have been characterized by (31)P, (13)C, and (27)Al MAS NMR. Nerve agents VX, GB, and GD hydrolyze to yield surface-bound complexes of their corresponding nontoxic phosphonates. At sufficiently high loadings, discreet aluminophosphonate complexes, Al[OP(O)(CH(3))OR](3), are generated which are identical to synthesized model compounds. Thus the reaction with phosphonic acids is not just surface-limited, but can continue to the core of alumina particles. HD mainly hydrolyzes at lower loadings to yield thiodiglycol (TG, 71%) and a minor amount of the CH-TG sulfonium ion (12%), although some elimination of HCl is also observed (17%). The reactive capacity for HD is evidently exceeded at high loadings, where complete conversion to TG is hindered. However, addition of excess water results in the quantitative hydrolysis of sorbed HD to CH-TG. On AP-Al(2)O(3) dried to remove physisorbed water, (13)C CP-MAS NMR detects a surface alkoxide consistent with that of TG.

The inactivation of rhodanese by nitrite and inhibition by other anions in vitro.

Cyanide detoxification in mammals occurs, in part, by sulfur transfer by rhodanese to form the less toxic thiocyanate. Thiosulfate and nitrite are often used in combination for the treatment of cyanide intoxication. This report shows that nitrite can inhibit the rate of sulfur transfer by rhodanese in vitro. Nitrate, chloride, sulfate, and acetate were also examined as inhibitors. Inhibition by nitrite appeared to be more complex than for the other anions tested. Closer examination showed that nitrite can inactivate the sulfur-free rhodanese. Our observation leads to the suggestion that, in vivo, either rhodanese is maintained in its more stable sulfur-substituted form or cellular compartmentalization prevents inactivation by nitrite.

Organophosphate-induced histamine release from mast cells.

To examine the hypothesis that soman intoxication leads to degranulation of mast cells with the release of histamine, we studied the effects of soman on rat peritoneal mast cells (RPMC) in vitro and in vivo. In vitro studies were performed with RPMC harvested from Edgewood rats, and challenged with soman (10(-8)-3 X 10(-3) M) in Tyrode's buffer. The RPMC exhibited a dose-dependent release of histamine, with maximal release of 50% at 3 to 6 X 10(-4) M. The release process is an active, secretory, noncytotoxic event, which is calcium and temperature dependent, requires metabolic energy and is influenced by intracellular levels of cyclic AMP. We next studied the in vivo effects of disodium cromoglycate (DSCG, 10(-4) M) on soman and Compound 48/80-induced histamine release. In vivo studies were performed by the i.p. injection of 5 ml of Tyrode's buffer containing soman (O-1 LD50), or Compound 48/80 as a positive control, with or without DSCG. The fluid recovered after approximately 10 min in the peritoneal cavity was examined for percentage of histamine release. In vivo, Compound 48/80 induced 49 +/- 1% histamine release, with no inhibition by DSCG (Compound 48/80 plus DSCG induced 49 +/- 0.4% histamine release). On the other hand, soman (1 LD50) induced 17 +/- 5% extracellular histamine release, with complete inhibition by DSCG (soman plus DSCG induced 3 +/- 1% histamine release). The data indicate that soman induced a dose-dependent release of histamine from RPMC, and provide evidence that histamine is a potentially important mediator of the pathophysiological response to organophosphate intoxication.(ABSTRACT TRUNCATED AT 250 WORDS)