Effects of chronic corticotrophin treatment on aldosterone metabolism in the rat.

Chronic treatment with high doses of ACTH leads to marked reduction in aldosterone biosynthesis and secretion both in vivo and in vitro. In contrast, it has been reported that peripheral plasma aldosterone levels may be elevated following prolonged ACTH treatment. The present study attempts to determine the reason(s) for this apparently paradoxical finding. ACTH treatment (40 micrograms/100 g body weight) of male Sprague-Dawley rats for 7 days caused a decrease of more than 90% in aldosterone secretion into the adrenal vein in vivo and aldosterone production by intact adrenal capsules incubated in vitro. In contrast, peripheral plasma aldosterone levels appeared to be increased when measured by radioimmunoassay using two different polyclonal antibodies (antibody 1 (AB1) raised against aldosterone-3-carboxymethyloxime-bovine serum albumin (BSA) and antibody 2 (AB2) raised against aldosterone-21-hemisuccinate-BSA). However, when a highly specific monoclonal antibody (raised against aldosterone-3-carboxymethyloxime-BSA and showing low cross-reactivity to aldosterone metabolites) was used, peripheral plasma aldosterone levels appeared to be reduced in ACTH-treated rats. Following chromatographic fractionation of peripheral plasma, significantly more material with aldosterone-like immuno-reactivity, but which was less polar than authentic aldosterone in chromatographic mobility, was detected in the fractions using antibodies AB1 and AB2. The absence of this material from fractions of adrenal vein plasma leads us to infer that this material is generated in the peripheral circulation, probably as a result of hepatic metabolism. In addition, the overall metabolic clearance rate (MCR) of [3H] aldosterone was found to be significantly decreased following prolonged ACTH treatment. We conclude that the seemingly discrepant findings with regard to the effects of chronic ACTH treatment on peripheral plasma aldosterone levels and the secretion of aldosterone in vivo can be reconciled by (1) the changes in the overall MCR of aldosterone and (2) the generation of increased quantities of aldosterone metabolites such as 5 alpha-dihydroaldosterone and 3 alpha, 5 beta-tetrahydroaldosterone which show significant cross-reactivity with some aldosterone antibodies.

Ijanikin: a study of environmental health in a rural Nigerian community.

Ijanikin is a typical Yoruba village in the rain forest belt area of Southern Nigeria. The childhood years in this community are fraught with the danger of numerous communicable diseases, compounded by inadequate supply of good quality foods to meet normal requirements and allow a margin of safety for the stress of infections. Overcrowding and poor ventilation in the houses are important factors in the spread of communicable diseases, while poor sanitation and deficient personal hygiene account for the heavy burden of intestinal parasitoses. Improvement in the health of this and other similar rural communities would require the provision of clean water supply, installation of essential sanitary facilities, provision of adequate food supply, and a well-planned and carefully executed health education programme.

ADP-ribosyltransferase in Plasmodium (malaria parasites).

The nuclei of Plasmodium yoelii nigeriensis contain an enzyme, ADP-ribosyltransferase, that will incorporate the ADP-ribose moiety of NAD+ into acid-insoluble product. The time, pH and temperature optima of this incorporation are 30 min, 8.5 and 25 degrees C respectively. Maximum stimulation of the enzyme activity is obtained with 1.0 mM-dithiothreitol or 2.0 mM-2-mercaptoethanol. Ca2+ and Mg2+ ions at optimum concentrations of 5 mM and 10 mM respectively stimulated the activity of the enzyme by 21% and 91%. The enzyme activity is, however, inhibited by 24% in the presence of 10 mM-MnSO4. The substrate, NAD+, exhibits an apparent Km of 500 microM, and the activity of the enzyme is inhibited by four chemical classes of inhibitors: nicotinamides, methylxanthines, thymidine and aromatic amides. The inhibitors are effective in the following increasing order: nicotinamide less than 3-aminobenzamide less than thymidine less than 5-methylnicotinamide less than theophylline less than m-methoxybenzamide less than theobromine. The enzyme activity is also inhibited by some DNA-binding anti-malarial drugs.

Characterization of a structural glycoprotein from bovine ligamentum nuchae exhibiting dual amine oxidase activity.

A structural glycoprotein has been extracted from bovine ligamentum nuchae by using 5 M guanidine hydrochloride containing a disulfide bond reducing agent and purified by preparative gel electrophoresis. The isolated material appeared to be monodisperse, with a molecular weight of approximately 34000, as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by analytical ultracentrifugation. It contains 10% carbohydrate comprising mannose, N-acetylglucosamine, galactose, and sialic acid in a 6:5:3:3 molar ratio. The glycoprotein has been assayed for peptidyl-lysine oxidase activity by using [3H]lysine-aortic elastin, prepared from 15- to 17-day-old chick embryos, as a substrate. In the absence of free lysine, the specific activity of the preparation over a 2-h incubation was approximately 60 X 10(4) dpm/mg of purified protein. Addition of 10 mM lysine resulted in an approximately 50% decrease in the specific activity. Free lysine was shown to act as a substrate for the glycoprotein preparation as indicated by control experiments using [3H]lysine in place of the aortic substrate. These results demonstrate that the glycoprotein exhibits a dual amine oxidase activity. In the presence of 0.27 mM beta-aminopropionitrile fumarate, a concentration which completely inhibits peptidyl-lysine oxidase activity in other lysyl oxidases, the glycoprotein preparation was inhibited by approximately 14%. In the absence of 5 M guanidine hydrochloride and reducing agent, the glycoprotein undergoes aggregation which in the presences of copper ions results in the formation of cylindrical tactoids, the diameter of which (11 nm) corresponds closely to that of the fibrils which in the majority of connective tissue matrices constitute the microfibrillar component mainly associated with elastic fibers.