R-[N-acetyl]eglin c:poly(oxyethylene) conjugates: preparation, plasma persistence, and urinary excretion.

In this paper, we describe the preparation, purification, and characterization of conjugates of R-[N-acetyl]eglin c (Eglin c) with poly(oxyethylene) (POE; Eglin c:POE). The plasma profile and urinary excretion of the conjugates has been determined after iv administration in mice. The modification of Eglin c with POE does not significantly impair the ability of Eglin c to bind elastase as measured by an in vitro assay. In the best example, 79% of theoretical activity was retained by the conjugate. The in vivo results clearly show that the amount of Eglin c:POE in plasma after iv administration is much higher than comparative doses of unconjugated Eglin c. The time course of the plasma concentration of the conjugate matches closely that of the corresponding free polymer. Consequently, we can expect that higher plasma concentration could be achieved, if and when required, by selecting polymers of appropriate size.

Reovirus 1 and 3 bind and internalise at the apical surface of intestinal epithelial cells.

Displacement of [125I]reovirus from the surface of L cells by homologous and heterologous reovirus serotypes has indicated the presence of two different receptors. Corresponding experiments with Caco-2 cells and apical membrane vesicles suggest either two different receptors or different affinity of each reovirus serotype for the same receptor. Binding and internalisation of reovirus at the apical surface of Caco-2 cells and apical membrane vesicles has been demonstrated and the implications of this for models of reovirus infectivity in the intestine are discussed.

An immunospecific enzyme assay for horseradish peroxidase.

A sensitive assay highly specific for horseradish peroxidase has been developed. The basic principle of the procedure is similar to that of the enzyme-linked immunosorbent assay technique. Sensitivity is the range 0.156-2.5 ng/ml. Background activity in undiluted plasma and lymph under these conditions is negligible.

Pharmacokinetics and metabolism of muramyl dipeptide and nor-muramyl dipeptide [3H-labelled] in the mouse.

The fates of 3H-muramyl dipeptide (MDP) and 3H-nor-MDP have been investigated after intravenous (i.v.), intraperitoneal, and subcutaneous injection of a range of doses in the mouse. After i.v. injection both compounds were cleared rapidly from the circulation, distributed initially to the tissues, and finally excreted largely intact in the urine. Most of the tissues contained intact material at 2 min after injection, but the much lower levels of radioactivity persisting at 1 h had undergone considerable metabolism (except in intestine, where some intact material persisted for as long as 24 h). Some accumulation of radioactivity was observed in liver and kidney and there were quantitative and qualitative differences between the two compounds. Characterisation of some of the metabolites in these tissues was undertaken, and the deamidated muramyl dipeptide was tentatively identified which is known to have some biological activity. The mechanism of the biological effects, which may be expressed over a relatively long time period, remains to be explained in view of the rapid excretion of most of the dose.

Fate of human corticotrophin immediately after intravenous administration to the rat.

The distribution and degradation of tritium-labelled human 1-39 corticotrophin have been studied after intravenous administration to the rat. Within 5 min of injection of single major metabolite, 3-39 corticotrophin, appears in the circulation. This metabolite, however, has only 3.6% of the steroidogenic potency of 1-39 corticotrophin and the evidence suggests that it is formed in muscle and skin. By 5 min, extensive degradation had occurred in all the major tissues in the body (muscle, skin, liver, kidney, gut).