The influence of dietary Ca on peak bone mass and on subsequent bone loss is controversial. Despite this an assessment of nutritional status is often included in the clinical evaluation of osteoporosis risk. To assess the value of this we investigated the relationship between current diet and bone mineral density (BMD) in 426 postmenopausal women, aged 45–59 years, who were enrolled into an international multi-centre trial of alendronate for the prevention of postmenopausal osteoporosis. BMD of the lumbar spine and proximal femur was measured on two occasions approximately 2 weeks apart by dual-energy X-ray absorptiometry. Serum osteocalcin was measured by immunoradiometric assay and serum 25-hydroxycholecalciferol by radioimmunoassay. Dietary assessment was performed by analysis of a 3d unweighed dietary record, using Salford University's Microdiet software. BMD at both the lumbar spine and femoral neck correlated significantly with BMI, age, and average serum osteocalcin concentration. We therefore corrected for these variables in subsequent analyses. Dietary Ca intake ranged from 223 to 2197mg/d (median 852mg/d). Neither dietary Ca intake nor any other nutritional variable correlated significantly with BMD. There was a weak, but significant correlation between Ca intake and serum osteocalcin. We conclude that current diet does not correlate with BMD in early postmenopausal women. However, present diet may affect the rate of change of BMD, and this is supported by the finding of a significant relationship between dietary Ca and serum osteocalcin, a marker of bone formation rate.

The influence of Na load on bone metabolism was investigated in postmenopausal women using urinary deoxypyridinoline (DPD) as a marker of bone resorption. In a cross-over study, fourteen postmenopausal women were divided into two groups of seven. A fixed diet providing 816 mg Ca/d with either 60 or 170 mmol Na/d was consumed. At the end of an 8 d period the groups switched diets for a further 8d period. Urine was collected daily for the last 4d of each period. There was no significant difference in DPD excretion between high-Na and low-Na diets (129 nmol/d v. 132 nmol/d; P = 0·18). There was, however, a significant relationship (P = 0·02) between the changes in DPD excretion and urinary Ca. Plasma Mg fell from 0·83 to 0·81mmol/l on the high Na intake (P<0·001), but there was no significant effect on plasma Ca or intact parathyroid hormone levels. It is concluded that varying dietary Na intake may affect Ca and Mg metabolism, but we were unable to demonstrate an effect on bone resorption at the levels of intake used

Ten adult female mink (Mustela vison) were studied in a 7 d balance experiment consisting of a 2 d pre-surgery feeding period, followed by surgery, 1 d of recovery, 4 d of ad libitum feeding, and a 2d fasting period. In this experiment (Expt A) the animals had osmoticpumps implanted for continuous release of radioactively-labelled p–aminohippuric acid (p–aminobenzoyl-2-[3H]glycine; [3H]PAH;n10) and 14C-labelled inulin ([14C]IN; n 5). Repeated 24 h collections of urine, corrected to 100%[3H]PAH or [14C]IN recovery, were used for accurate determination of N balances, 24 h urinary excretion of urea, creatinine, and total N, and calculation of mean 24 h renal clearance rates for endogenous creatinine and inulin. N balances were slightly below zero, but not significantly different between feeding and fasting periods, indicating that correction to 100% [3H]PAH recovery resulted in slight overestimation of thefinal balances. During fasting, withdrawal of the dietary water and protein loads resulted in a dramatic decline in 24 h urinary volume, and urea and creatinine excretion. Large individualvariations in 24h urinary creatinine excretion (with relative variation coefficients up to 30%) confirmed that this is an unreliable index of the completeness of urine collection. In this respect, recovery rates of [3H]PAH proved far more consistent. Renal clearance values obtained in fed mink were in fair agreement with published data from cats, dogs and ferrets (Mustela putorius furo). Inulin clearance was about 30% higher than endogenous creatinine clearance, although its decline in response to fasting was not significant. In a separate study (Expt B)another ten female mink were equipped with osmotic pumps containing [3H]PAH for determination of 24 h excretion rates of purine derivatives. During feeding, allantoin accounted for more than 97 % of the excretion of purine derivatives in urine, uric acid making up less than 2·5%, xanthine and hypoxanthine less than 1 %. In fasted animals, urinary excretion of each of these purine derivatives declined to less than 50% of the feeding value. In conclusion, an experimental technique is presented for efficient and accurate measurements of daily urinary excretion of nitrogenous constituents, which allows for correct determination of N balances in adult mink and, presumably, in other mammalian species.

The aim of the study was to evaluate the functional role of reticular contractions for digesta passage in sheep. Feed intake, mean retention time of fluid and plastic particles in the reticulo-rumen, rumen fluid volume, forestomach motility and particle size distribution in the faeces were determined in five rumen-fistulated sheep fed on hay ad libitum (Expt 1). The same variables were determined when reticular movements were impaired for 10 d by introducing a silicone-covered lead weight (500 g) into the reticulum (Expt 2). As feed intake dropped in Expt 2 by 27% compared with Expt 1, the sheep received in an additional experiment exactly the amount of feed which had been consumed during Expt 2 and measurements were repeated without impairing reticular movements (Expt 3). The introduction of the weight did not affect the frequency of A- or B-cycles, but elevation of the reticular floor in a cranio-dorsal direction during the biphasic contraction was markedly reduced. The pattern of marker excretion indicated a drastically changed composition of reticular outflow in Expt 2 compared with Expts 1 and 3. During Expt 2, rumen fluid volume was similar to that in Expt 1 but about 25% higher than that in Expt 3; the amount of large feed particles in the faeces was increased compared with Expt 1 ( + 49%) and Expt 3 ( + 76%). In at least two sheep, abomasal emptying was inhibited during Expt 2, as indicated by an enlarged impacted abomasum. In conclusion, the results emphasize the central role of reticular motility for the separation of particles in the forestomach, the outflow of digesta from the reticulo-rumen and transpyloric digesta flow.

Broiler chicks were fed on chemically-defined crystalline amino acid diets containing graded levels of L-threonine (Thr) during the period 10–20 d post-hatching. Doses of Thr represented 5,10,15,40,55,70 and 95% of its ideal level for maximal weight gain and feed efficiency. Other amino acids were maintained at minimized excess levels that were 15% (of ideal) above the various doses of Thr. Following 10d of feeding and a 24h fast, chicks were killed for whole-body protein and amino acid analysis. Using pen accretion means, weight gain (r20·98), protein accretion (r2 0·99), and Thr accretion (r2 0·99) were linear (P<0·01) functions of Thr intake. Slope of the Thr accretion regression line indicated that 82% of the Thr intake was recovered in whole-body protein. At zero Thr intake, chicks lost 11·9 mg Thr/d. The Thr maintenance requirement was 45·7 mg/d per kg body weight 0·75. Increasing doses of Thr resulted in increased (P<0·05) concentrations of methionine, isoleucine, histidine and lysine in whole-body protein. Other indispensable amino acids, including Thr, also tended to increase. Whole-body glycine, proline, serine and cystine concentrations decreased (P<0·05) as Thr was increased in the diet. The maintenance need for Thr represented 5·5% of the total need for Thr. The data suggest that efficiency of Thr utilization is constant at all levels of Thr intake between 5 and 95% of the level required for maximal weight gain and feed efficiency.

It is becoming well established that poor fetal and early postnatal growth can have long-term effects on adult health, including susceptibility to non-insulin-dependent diabetes mellitus, cardiovascular disease and hypertension. It is suggested that this results from poor nutrition during early life having permanent effects on the structure and metabolism of certain organs and tissues. In the present study we investigated the effect of a low-protein diet during pregnancy and lactation on adipocyte properties and glucose tolerance. Rat dams were fed on a diet containing either 200 (control) or 80 (low protein) g protein/kg during pregnancy and lactation. In addition cross-fostering techniques were employed to enable a separate evaluation of the prenatal and postnatal periods. All offspring were weaned onto a 200 g protein/kg diet at 21 d of age and then studied at 6 weeks of age. The mothers' protein supply during lactation appeared to be the most critical time window for longterm growth. In contrast, the offspring of mothers fed on a low-protein diet during pregnancy or lactation were significantly more glucose tolerant than controls, suggesting that both time windows can have long-term effects on glucose tolerance. In addition off spring of mothers fed on a lowprotein diet during pregnancy or lactation had significantly smaller adipocytes than controls. However the largest reduction in adipocyte size was observed when there was a low-protein diet during both pregnancy and lactation. The amount of insulin receptor present in adipocyte membranes was increased in the three animal groups that had been exposed to the low-protein diets while levels of the insulin responsive glucose transporter (GLUT 4) were similar in adipocyte membranes from all groups.

The amount of energy mobilized or stored as protein, expressed as a proportion of the total energy stored or mobilized (defined as the P ratio, Payne & Dugdale, 1977), was investigated in the young male (rapid growth) and adult female (slow growth) rat. Energy mobilization was induced by a 3 d fast and the changes in body content of fat and lean tissues were used to estimate the fasting P ratio (Pfast). Tissue storage was subsequently effected by 17 d of refeeding and the corresponding ratio (Prefed) was calculated from the amounts of lean and fat tissue regained. The same experimental protocol was used for measuring Pfast and Prefed in weanling (30d) and adult (130d) rats. Weight-matched individuals were assigned to three groups. All animals in group 1 were killed at the beginning of the experiment. Animals in group 2 were fasted for 3d and then killed. Group 3 animals were first fasted for 3d, then had free access to a stock diet for a further 17 d before being killed. During fasting, a close linear relationship was found between weight change and body energy changes (r 0·985, and r 0·92, P < 0·001 for weanlings and adult rats respectively) and between carcass N loss and urinary N loss (r 0·933, P < 0·001). These relationships were used to estimate the body energy and N content of each animal at the end of the initial fasting period. Hence, both Pfast and Prefed values could be calculated for all individuals at both ages. When Pfast and Prefed were calculated for adult rats, the mean values were similar (0·138 (SE 0·002) and 0·130 (SE 0·006) respectively). Individually, the Pfast, and Prefed values were correlated (r 0·54, P = 0·058). In weanling rats, the mean Prefed value was about 2·5 times the Pfast (0·421 (SE 0·0113) v. 0·156 (SE 0·004)). Despite the differences in Pfast and Prefed, the individual values were again correlated (r 0·668, P < 0·05). These results support the suggestion made by Payne & Dugdale (1977), that particular P- ratio values are characteristic of individuals and describe the extent to which protein is mobilized or stored during fasting or refeeding. These observations are discussed in relation to the predictions made by the Payne-Dugdale model.

Dodecanedioic acid (C12), a saturated aliphatic dicarboxylic acid with twelve C atoms, was given as an intraperitoneal bolus to male Wistar rats, with the aim of evaluating C12 suitability as an energy substrate for parenteral nutrition. The 24 h urinary excretion of C12 was 3·9% of the administered dose. C12 kinetics were investigated by a one-compartment model with saturable tissue uptake and reversible binding to plasma albumin. The analysis of plasma concentration and urinary excretion data from different animals yielded the population means of the kinetic parameters: renal clearance was 0·72ml/min per kg body weight (BW) (much smaller than inulin clearance in the rat), and maximal tissue uptake was 17·8 μmol/min per kg BW corresponding to 123·7 J/min per kg BW. These results encourage the consideration of C12 as a possible substrate for parenteral nutrition. To investigate the effect of C12 administration on glucose kinetics, two other groups of rats, one treated with an intraperitoneal bolus of C12 and the other with saline, were subsequently given an intravenous injection of D-[U-14C]glucose in a tracer amount. Radioactivity data of both control and C12-treated rats were analysed by means of a two-compartment kinetic model which takes into account glucose recycling. The estimates of glucose pool size (2·3 mmol/kg BW) and total-body rate of disappearance (82·1 μmol/min per kg BW) in control rats agreed with published values. In C12-treated rats, the rate of disappearance appeared to be reduced to 36·7 μmol/min per kg BW and the extent of recycling appeared to be negligible.

The efficacy of parenteral nutrition could be improved by finding a more effective energy source. Esters of short-chain fatty acids have exhibited some promise as alternatives to glucose. The present study reports on two new esters and one amide, each containing acetoacetate as the organic acid. The three compounds: glyceryl bisacetoacetate, N-2',3'-dihydroxypropyl-3-oxo-butanamide (1-acetoacetamido-2,3-propane diol), and partially reduced glucosyl pentaacetoacetate, were synthesized and then continuously infused into rats for 7d. The infusion rate provided 50% of the rats' estimated metabolic energy requirement, and rats were fed with a reduced-energy oral diet that provided the remaining 50% of energy plus adequate protein. Rat groups for each compound were: (1) experimental-compound-infused and ad libitum-fed, (2) isoenergetic glucose-infused and pairfed, and (3) saline infused and pair-fed. Body-weight changes, N losses and N retention were measured daily. All rats died from partially reduced glucosyl pentaacetoacetate infusion at 100% and 50% of the intended rate. Rats infused with l-acetoacetamido-2,3-propane diol failed to gain weight and to increase the plasma ketone-body concentration. Glyceryl bisacetoacetate produced hyperketonaemia, and weight gain and N variables that were similar to those for glucose-infused rats. It was concluded that only glyceryl bisacetoacetate would make a satisfactory parenteral nutrient.

We compared the effects of idiorrhythmic dose-rate feeding and conventional dose-response on the induction of intestinal metallothionein (IMT), expression of aortal heat-shock protein mRNA (HSP70mRNA) induced by restraint stress, and accumulation of Zn in the femur and incisor of young growing male rats. An idiorrhythmic approach requires that the average dietary Zn concentration (modulo, M) over the whole experiment (epoch, E) is kept constant across different groups. This is done by adjusting the Zn concentration of the supplemented diet supplied to compensate for the reduction in the number of days on which Zn-supplemented diet is fed, the latter being spread evenly over the experiment. Idiorrhythms involve offering the diet with n times theoverall Zn concentration (M) only every nth day with Zn-deficient diet offered on other days. Idiorrythmic Zn dose-rate feeding changed Zn accumulation in the femur and incisor in a complexbi-modal fashion, indicating that metabolic efficiency of dietary Zn is not constant but depends on Zn dose-rate. In contrast to feeding Zn in the conventional dose-response scheme, iMT and HSP7OmRNA were not affected by idiorrhythmic dose-rate feeding. Idiorrhythmic cycling in dietary Zn load posed no risk of a biochemical overload nor caused the animals to be stressed. Idiorrhythmic dose-rate feeding brings the dimension of time to the conventional dose-response