Abstract: THE pattern of the metabolic response of man to injury (for example, fracture of a long bone), in particular its effect on protein catabolism, has been under investigation for some time by one of us1 as this phenomenon is of basic importance to our understanding of protein metabolism in general. The reaction is characterized in man by a marked increase in the urinary excretion of nitrogen and sulphur, which reaches a peak from the fourth to the eighth day after the injury and then slowly declines. There is also a loss of phosphorus and potassium. This phenomenon has been confirmed by many workers and in other forms of injury2. Cuthbertson, McGirr and Robertson3 have also found the same thing to occur in the rat, though rather earlier. The losses appear to be more general than local in origin.

Abstract: IT has been shown that 8-hydroxyquinoline is not toxic for Staphylococcus aureus unless traces of iron (or copper) are present in the medium (Rubbo, Albert and Gibson, 1950). It was next shown that a large excess of either iron or oxine prevented a rapid bactericidal action. This led to the hypothesis that oxine gained access to the cells as a complex having one atom of the metal bound between two molecules of oxine (to be referred to briefly as the 1: 2 complex (XIII)); and that it exerted its toxic effect inside the cells in the form of the unsaturated complex which consists of one molecule of oxine bound to one atom of the metal (i.e., the 1: 1 complex (XII)) (Albert, Gibson and Rubbo, 1953). It will be noted that this hypothesis postulates that oxine acts within the cell, and not on the outside as the aminoacridines do (Albert, 1951). The present work was carried out to test that assumption by varying the lipophilic nature of oxine by means of suitable substituents in the molecule. It is generally agreed that in a series of related substances the ease of penetration through a cell membrane is proportional to the lipophilic nature of the substance (Davson and Danielli, 1943; Hober, 1945). This lipophilic nature can be conveniently measured in terms of oil/water partition coefficients. In the present work the coefficient of oxine has been lowered by the insertion of one or more ring-nitrogen atoms, and the coefficients of some of the resulting substances have been raised again by the insertion of alkyl groups. It will be shown that the antibacterial properties disappear as the coefficient is lowered, and re-appear when it is raised again. These facts provide support for the hypothesis that oxine acts inside the cell.