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D N Kalu

Publications and source records attributed to D N Kalu.

At least 73 records · Page 4Linked to original sources
PubMed1984

Comparison of the effects of DHEA and food restriction on serum calcitonin.

In the first of two studies, female Wistar rats were fed ad libitum or 60% of the ad libitum intake. In the second study, female Sprague Dawley rats were given subcutaneous injections of DHEA (2-4 mg/day) five times per week or received similar volumes of the solvent vehicle. Animals in both studies were maintained on their respective regimens for six months. At the termination of the study, the food restricted animals weighed significantly less than the animals fed ad libitum; in addition, their serum calcitonin concentration was markedly lower and was over 60% less than that of the ad libitum fed animals. In contrast, DHEA treatment had no significant effect on the body weight or on the plasma calcitonin of the Sprague Dawley rats. Since food restriction maintains calcitonin concentrations toward youthful levels, it is clear that at least one of the anti-aging effects of food restriction is not mediated by DHEA.

Aging↗
PubMed1984

Evaluation of the pathogenesis of skeletal changes in ovariectomized rats.

Young adult ovariectomized rats were used to investigate the pathogenesis of ovarian hormone deficiency osteopenia, uncomplicated by other forms of age-related bone loss. It was observed that the femurs of ovariectomized rats were less dense with less hydroxyproline and less calcium (Ca) and phosphorus per unit volume of bone than those of age-matched controls. Compared to animals killed at the beginning of the study to serve as baseline controls, ovariectomized rats and their age-matched controls had increased periosteal and cortical areas, but in contrast to the age-matched controls, ovariectomized rats had markedly increased medullary area and the ratio of their cortical area to periosteal area was decreased (P less than 0.02). When the changes in cross-sectional areas were expressed as percent of the baseline levels, the medullary area was increased 32% in ovariectomized rats, and only 14% in the age-matched controls; the net increase in cortical area was 17% for the controls and 11% for the ovariectomized rats and there was only 3% difference between the increases in their periosteal areas. Furthermore, ovariectomy caused a marked decrease in serum calcitonin and Ca levels but not in PTH levels. As expected, PTH administration increased serum Ca in all rats, but the rise was greater in ovariectomized calcitonin-deficient rats than in rats that were only ovariectomized or only thyroidectomized. Whereas these findings support the concept of increased sensitivity of bone to PTH in ovarian hormone deficiency osteopenia, the decrease in serum Ca in ovariectomized rats indicates that other factors may be involved as well.

Animals↗
PubMed1984

Aging and dietary modulation of rat skeleton and parathyroid hormone.

Studies were carried out on SPF F344 male rats to evaluate the effects of aging and life-prolonging food restriction, without malnutrition, on rat skeleton and circulating PTH. Six-week-old F344 rats were divided into five groups. Group 1 rats were fed ad libitum a diet that contained 21% protein. Group 2 rats were fed 60% of the mean food intake of group 1 rats from 6 weeks of age for the rest of their lives. Group 3 rats were fed 60% of the ad libitum food intake until 6 months of age and then switched to ad libitum feeding. Group 4 rats were fed ad libitum until 6 months of age, and then switched to 60% of the ad libitum food intake. Group 5 rats were fed ad libitum a diet that contained only 12.6% protein so that these animals ingested the same amount of protein per day as the group 2 rats. In group 1 animals, bone length, weight, density, and calcium content increased rapidly with age and plateaued at about 12 months of age. There was no evidence of bone loss in these animals until about 24 months of age, but by 27 months, the animals had lost appreciable amounts of bone. The circulating immunoreactive PTH levels of the animals increased with advancing age, with a marked rise at 27 months. The age-related changes in bone and serum PTH levels of rats in groups 3 and 5 were similar to those of group 1 animals, except that a terminal increase in serum PTH did not occur in group 5 rats. In the groups 2 and 4 animals which were food restricted for the longest period, bone growth and maturation were slowed down, but the animals did not experience senile bone loss or marked terminal increase in circulating PTH. The salutary effects of food restriction were, therefore, not due specifically to the restriction of protein intake or to restricting food intake only during the period of rapid growth.

Aging↗
PubMed1983

Lifelong dietary modulation of calcitonin levels in rats.

Studies were carried out on specific pathogen-free rats to evaluate the effects of aging and dietary manipulation on serum and thyroid calcitonin (CT) levels. Male Fischer 344 rats were randomized at 6 weeks of age to six dietary groups and subsequently maintained on the following dietary regimens. Group 1 rats were fed ad libitum throughout life; group 2 rats were fed 60% of the ad libitum food uptake, but received the same amounts of calcium, phosphorus, and vitamin D; group 3 rats were fed as the group 2 animals until 6 months of age and from then on were fed ad libitum; group 4 rats were fed ad libitum until 6 months of age and then switched to 60% food restriction; group 5 rats were fed ad libitum on food isocaloric with that of group 1 rats, but containing only 60% of the protein. Group 6 rats were killed at 6 weeks of age to serve as baseline controls. Ten rats were killed in each of the remaining five groups 15 h postprandial at 6-month intervals. The following observations were made. Serum CT increased with age similarly in the ad libitum fed group 1 and 5 rats. Food restriction markedly inhibited the increase in serum CT, and the effect was more profound in animals whose food intake was restricted after 6 months of age (group 4) than in animals on lifelong food restriction (group 2). In rats switched from food restriction to ad libitum feeding (group 3) at 6 months of age, serum CT increased with age to levels identical with those of lifelong ad libitum fed group 1 animals. Thyroid CT showed a similar pattern of age-dependent and dietary modulated changes. In contrast, aging and dietary modulation had no appreciable effect on serum calcium levels, except at 27 months of age when the serum calcium level of group 1 animals increased dramatically from the level for 24-month-old animals. There was a weak positive correlation between serum calcium and serum CT (r = 0.627; P = 0.02) and a highly significant positive correlation between serum CT and thyroid CT (r = 0.917; P = 0.001). These findings indicate that elective and therapeutic restriction of food intake might also attenulate CT levels in humans, with potentially adverse implications for skeletal homeostasis.

Aging↗
PubMed1980

Calcium regulatory action of endogenous rat calcitonin demonstrated by passive immunization with calcitonin antibodies.

The calcium regulatory role of calcitonin (CT) in murine physiology was evaluated with a combination of immunological techniques, bioassays, and gland ablation. Passive immunization of rats with neutralizing CT antibodies caused an immediate but transient increase in plasma calcium with a time course similar to that observed in thyroparathyroidectomized animals. In animals fasted during the day and fed at night (1700-0700 h), acutely decreasing endogenous CT (< 100 pg/ml) by thyroparathyroidectomy or by passive immunization with CT antibodies resulted in a greater increase in plasma calcium in the preprandial (1600 h) than in the postprandial inverse correlation between immunoreactive CT and plasma calcium, a known secretagogue for CT. In these animals on a restricted feeding schedule, a sharp preprandial (1600 h) rise in immunoreactive and bioactive CT and a circadian rhythm in plasma calcium were also observed. The onset of the increase in circulating CT preceded the onset of feeding and coincided with or shortly preceded the daily nadir of plasma calcium. These findngs establish that CT has a primary calcium regulatory role in murine physiology. More specifically, they demonstrate that 1) the postthyroparathyroidectomy increase in plasma calcium is due specifically to the loss of CT, 2) passive immunization is a feasible technique for evaluating the actions of endogenous CT, 3) the role of CT in calcium regulation cannot be restricted to that of preventing prandial and postprandial increase in blood calcium, and 4) factors other than calcium must be involved in the control of CT secretion in the nonfed state.

Animals↗
PubMed1976

Regulation of plasma calcium in rats: age-related roles of PTH and calcitonin.

To determine the influence of aging on the relative roles of parathyroid hormone (PTH) and calcitonin in the control of calcium homeostasis during fasting, we assessed changes in plasma calcium in fasted rats following simultaneous removal of the glands that secrete both hormones. Animals ranging in age from 3 to 34.7 wk were thyroparathyroidectomized or sham operated and bled by orbital puncture prior to and 1.5, 3, and 6 h after surgery. After thyroparathyroidectomy (TPTX), plasma calcium fell immediately and progressively in very young rats (3-6 wk old); in young animals (6.5-9.4 wk old), there was a delay of about 1.5 h pceded by a rise, which persisted for at least 3 h. Since the rise and fall in plasma calcium after TPTX are most likely due to calcitonin and PTH deficiencies, respectively, our observations are consistent with the following hypothesis; in the fasting state, the relative importance of calcitonin and PTH in the regulation of plasma calcium varies with age; PTH appears to play the dominant role in young rats; however, during maturation the importance of calcitonin appears to increase progressively.

Age Factors↗
PubMed1976

Further studies on the hypercalcemic effect of acute calcitonin deficiency in rats.

Studies were carried out to determine the origin of the immediate increase in plasma calcium following acute calcitonin deficiency in mature rats. Animals were pre-labelled with 45calcium 24 hours and 4 weeks before thyroparathyroidectomy (TPTX) and 1 hour, 24 hours, 2 and 4 weeks before nephrectomy and TPTX and bled serially over the following 3 hours. In each study the final average weight of the rats was over 300 g. Plasma calcium increased after TPTX. In rats labelled with 45calcium 1 and 24 hours previously, the rise was to small to alter the specific activity of calcium although radiocalcium was unchanged. In contrast, in animals pre-labelled with 45calcium 2 and 4 weeks before TPTX, the increase in stable calcium was associated with a parallel increase in radiocalcium. Consequently, the specific activity of plasma calcium did not differ appreciably from that of controls. These findings confirm the theory that in mature unfed rats acute calcitonin deficiency results in an immediate rise in plasma calcium. Since this increase is due mainly to enhanced transport of calcium from deep bone, our observations are in accord with the view that calcitonin decreases plasma calcium primarily by inhibiting calcium transport from "stable" bone.

Animals↗
PubMed1975

Evidence for physiological importance of calcitonin in the regulation of plasma calcium in rats.

To determine the physiological importance of calcitonin in the regulation of plasma calcium, studies were carried out in fasting animals to (a) assess the acute effects of thyroparathyroidectomy (TPTX) and thyroidectomy (TX) on plasma and urinary calcium; (b) investigate whether the changes in plasma calcium produced by removal of the glands were dependent on the presence of the kidney; and (c) determine if the effect of TPTX on plasma calcium is affected by age. Except where otherwise indicated, all studies were carried out on fasting male Wistar rats weighing over 300 g. The following observations were made. (a) TPTX and TX caused an increase in plasma calcium in nephrectomized animals. (b) This increase was not dependent on nephrectomy since in intact animals bearing autoparathyroid transplants TX also caused a significant rise in the mean plasma calcium level (0.37 mg/100 ml at 1 1/2 h). (c) Urinary calcium increased twofold in the 3-h period immediately after TX. (d) In unnephrectomized immature (50-g) rats, TPTX caused a progressive decrease in plasma calcium in contrast to old (360-g) rats, where a significant fall observed at 6 h was preceded by an increase in plasma calcium (0.5 mg/100 ml at 1 1/2 h). From these observations we conclude that: (a) calcitonin must play an important physiological role in the regulation of plasma calcium since the termination of its basal secretion caused an immediate but transient increase in plasma calcium in old unfed rats; (b) the relative importance of calcitonin and parathyroid hormone in the acute regulation of plasma calcium is age-related; and (c) the action of parathyroid hormone on bone may be modified by changes in ambient calcitonin concentration.

Aging↗
PubMed1975

Effect of calcium deprivation on parathyroid hormone-mediated bone and kidney contributions to the maintenance of plasma calcium in rats.

This study was designed to investigate the roles of bone and kidney in the acute regulation of plasma calcium by parathyroid hormone (PTH) during prolonged calcium deprivation. The effect of PTH was assessed by gland ablation. Animals were thyroparathyroidectomized or sham-operated and their urine was collected for 3 h. Subsequently they were anaesthetized and bled from the abdominal aorta. In rats fed on a low calcium diet, urinary hydroxyproline excretion was enhanced and, unlike animals fed on a normal diet, decreased 3 h after thyroparathyroidectomy (TPTX). In addition TPTX decreased plasma calcium by 0-45 mg/100 ml in normal rats compared with 1-94 mg/100 ml in animals fed on a calcium-deficient diet. Urinary calcium increased by 161 and 12 mug and accounted for 82 and 1-4 % of the fall in plasma calcium in normal and calcium-deprived animals respectively. The corresponding contributions of bone were 18 and 98-6%. These findings support the view that with prolonged calcium deprivation in adult rats, the relative contributions of bone and kidney to the acute regulation of the plasma calcium level by PTH are reversed. As a result, bone rather than kidney becomes the more important organ. At the same time non-PTH-mediated kidney reabsorption of calcium is increased.

Animals↗