Methanol half-life during ethanol administration: implications for management of methanol poisoning.

STUDY OBJECTIVE: To determine the half-life of methanol in methanol-poisoned patients who are treated with ethanol but not with hemodialysis. DESIGN: Case series. SETTING: University Hospital, University of Manitoba. PARTICIPANTS: Three methanol-poisoned patients treated with ethanol but not with hemodialysis and three similar patients identified by a literature review. RESULTS: Plots of terminal concentration versus time data were inconsistent with zero-order kinetics and were adequately explained by an apparent first-order process. The median half-life of methanol in these patients was 43.1 hours, with a range of 30.3 to 52.0 hours. CONCLUSION: Because of the significantly increased risk of toxicity and complications during ethanol monotherapy, we suggest that hemodialysis be considered for methanol-poisoned patients who are treated with ethanol infusion.

Iodination of [Tyr8]-bradykinin-comparison of chloramine-T and lactoperoxidase techniques.

Antigen-antibody kinetics were studied using a hapten which was iodinated by two unique procedures. Using bradykinin, a vasopressor hormone as a model peptide, radioactive iodination (125I) of its 8-tyrosyl analogue was carried out both enzymatically and chemically using modified procedures. Two distinct chemical species were obtained which were characterized on a chromatographic, chemical as well as charge basis as a mono-iodinated form of [Tyr8]-bradykinin using the lactoperoxidase procedure and a di-iodinated entity using chloramine-T technique. The addition of a second iodine atom to the antigen lowers its immunoreactivity for its antibody and thus alters the kinetics of this reaction. Further experiments on the stability (temperature, time of storage, and chemical environment) of these iodinated peptides are described.

Improved serum-initiated aspartate aminotransferase assay by inhibition of lactate dehydrogenase with oxamate.

We describe a serum-inititated aspartate aminotransferase (EC 2.6.1.1) assay that obviates the need for added lactate dehydrogenase (EC 1.1.1.27) in the reagent system. Interference from the oxidation of NADH by endogeneous lactate dehydrogenase is eliminated by adding sodium oxamate, a competitive inhibitor of the enzyme. The advantages of oxamate inhibition over lactate dehydrogenase addition are a shorter preincubation period, an increase in the linear range from less than 600 to more than 1400 U/L, no interference from above-normal concentrations of ketoacids, and elimination of bias between serum-initiated and the standard oxoglutarate-initiated assays for aspartate aminotransferase.

Immunological and biological activities of fragments and analogs of bradykinin.

Using a number of analogs and fragments of a short-chain peptide bradykinin, a series of experiments have been carried out to assess the effect of modifications to the basic structure of the parent molecule on its myotropic and immunoreactive properties. Binding kinetics of both an antibody raised against the authentic nonapeptide and its specific biological receptor found in the guinea pig ileum were used to study these alteration effects. Peptide derivatives of bradykinin with an extension at the N-terminal (Lys- and Met-Lys-bradykinin) cross-react with the antibody raised to bradykinin 59 and 70% respectively. On the other hand, internal fragments with intact C-termini (2-9 and 3-9 bradykinin) react with this same antibody to an extent of 250 and 875% respectively, indicating that they are more potent antigens than the vasopressor molecule itself. Other internal fragments, as well as 9-substituted analogs effectively and not interact. These results indicated that the C terminal arginine of bradykinin is indeed essential in the binding mechanism with its antibody. This in turn illustrates the role of the carrier ovalbumin in the development of antiserum to the ovalbumin-toluene-diisocyanate-bradykinin complex. The physiological experiments with the guinea pig bioassay preparations lead to similar conclusions. Most internal fragments of bradykinin are devoid of activity, whereas N-terminal fragments (2-9, 3-9, and 5-9 bradykinin) have retained some activity again indicating a need for an intact arginine residue at the C-terminus of the molecule. Any modification in position 9 results in severe impairment of biological activity. Thus, the C-terminal residue of bradykinin must be conserved in order that the molecule may retain its immunological and physiological activities. Any extensions, deletions, or modifications of this site will severely retard these functions.