The evaluation of novel mixed metal hydroxy-carbonates as phosphate binders: an in-vivo study in the rat.

A number of novel phosphate binders based on mixed metal hydroxide structures incorporating Fe and Ca, or Fe and Mg (classified as CT, Crosfield test compounds), were compared with the established phosphate binders Mg(OH)2, Al(OH)3, CaCO3 and a commercial hydrotalcite (Al- and Mg-based) using a rat model. The changes in urine and soluble faecal phosphate were used to evaluate efficacy of phosphate binding. The binders were mixed into a standard rat maintenance food at a concentration of 1% (w/w). Four rats were used for each binder study group and fed over 7 days. Urine and faeces were collected (in a metabolic cage) over the last 24-h study period and the phosphate content measured. The urinary phosphate was significantly reduced (P < 0.001) with CTFeCa (72+/-44 microm), CTFeMg (13+/-4 microm), CT100 (26+/-11 microm), and Mg(OH)2 (65+/-53 microm), compared with control (766+/-188 microm), Al(OH)3 (1,256+/-279 microm), and CaCO3 (857+/-25 microm). The soluble phosphate content of the faeces was significantly reduced (P < 0.05) by up to 60 % with CTFeCa, CTFeMg and Mg(OH)2, and up to 40% with CT100 and Al(OH)3, compared with 30% in controls and 10% with CaCO3. The new mixed metal hydroxy-carbonate compounds based on FeCa or FeMg are effective phosphate binders in-vivo and warrant further testing in patients.

The development and in-vitro evaluation of novel mixed metal hydroxy-carbonate compounds as phosphate binders.

The currently available phosphate binders are relatively inefficient and suffer from clinical side-effects of increased absorption of calcium and aluminium and the diarrhoea-inducing effects of magnesium. A new class of compounds based on mixed metal hydroxides has been developed and evaluated for their potential as phosphate binders. The mixed metal hydroxides were prepared using a standard procedure for hydrotalcite (Al2Mg6(OH)16.CO3.4H2O) by substituting Fe3+ for Al3+, with Mg2+ or Ca2+ as the divalent metal ion. Phosphate precipitation (binding) was examined at different pH values in aqueous solution and in various food mixtures in comparison with hydrotalcite, Al(OH)3, CaCO3 and Mg(OH)2 on the same weight-to-weight basis. A series of compounds with differing ratios of metal ions (Fe:Mg/Ca 1:2 or 1:3) gave analytically similar ratios to those predicted from the initial amounts added. CTFeCa bound > 90% phosphate in aqueous solution compared with 65% binding with CTFeMg, 85% binding with Mg(OH)2, and less than 30% binding for CaCO3 and Al(OH)3. The mixed metal compounds also bound up to 80% phosphate in various food matrices, which was relatively independent of changes in pH, compared with Mg(OH)2, where binding decreased from 85% at pH 3.0 to 25% at pH 8.0. Al(OH)3 and CaCO3 were relatively ineffective phosphate binders under all the conditions tested. The mixed metal hydroxides compounds show considerable promise as phosphate binders over those currently available and warrant further patient-based in-vivo testing.

Effect of nicotine on large bowel mucus thickness, eicosanoids and faecal proteinase in ferrets.

BACKGROUND: Following observations on the effect of subcutaneous nicotine on rectal mucosal eicosanoids and mucus in the rabbit we have repeated the work in ferrets which may be a more suitable animal model. AIMS AND METHODS: The effect of nicotine on mucosal eicosanoids, the adherent mucus layer, and faecal proteinases in the large bowel of ferrets was examined in forty animals randomly allocated to five groups, a control and four treatment groups. They were given subcutaneous saline or nicotine via an Alzet pump in doses of 0.3, 0.6, 1.2 and 2.0 mg/kg/day for 10 days and then sacrificed; measurements were made of serum nicotine and cotinine levels, rectal mucosal eicosanoids, adherent rectal and colonic mucus thickness, and faecal proteinases. RESULTS: No significant differences were observed for any measurements, except for serum nicotine and cotinine levels, which were raised consistent with the dose given. CONCLUSION: Nicotine had no effect on measurements, which may possibly be important in the relationship between smoking and ulcerative colitis.

Maternal performance of Hereford, Brangus, and reciprocal crossbred cows under semidesert conditions.

Maternal performance of 134 Hereford (H), Brangus (B), and reciprocal crossbred (H x B and B x H) cows from 2 to 7 yr of age was evaluated under semidesert conditions in this study. Calves produced by 2- and 3-yr-old cows were sired by Brangus and Hereford bulls. Calves produced by 4- to 7-yr-old cows were sired by Charolais bulls. Breed of sire and breed of dam of cow affected kilograms of weaning weight, 205-d weight, weaning weight as a percentage of cow weight, and 205-d weight as a percentage of cow weight produced annually. Brangus (either as sire or dam of cow) was superior to Hereford in all cases. Observed maternal heterosis on 2- to 3-yr-old cows was 23.0, 20.1, 30.0, 29.1, 23.9, and 23.0% for calf birth date, weaning percentage, weaning weight per year, 205-d weight per year, weaning weight as a percentage of cow weight per year, and 205-d weight as a percentage of cow weight per year, respectively (P less than .01). Observed maternal heterosis from mature cows was 19.8, 12.8, 21.0, 18.7, 17.4, and 15.4% for calf birth date, weaning percentage, weaning weight per year, 205-d weight per year, weaning weight as a percentage of cow weight per year, and 205-d weight as a percentage of cow weight per year, respectively (P less than .01). Results indicate large heterotic effects on annual cow productivity and an adaptive advantage for cows with Brangus sires and(or) dams under semidesert conditions.