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D N Kalu

Publications and source records attributed to D N Kalu.

At least 55 records · Page 3Linked to original sources
PubMed1991

Preexisting bone loss associated with ovariectomy in rats is reversed by parathyroid hormone.

Previous studies have demonstrated that when parathyroid hormone (PTH) administration to rats is started immediately following ovariectomy, it prevents bone loss due to ovarian hormone deficiency. In this study, we examined whether bone loss induced by ovariectomy could be reversed by parathyroid hormone if hormone therapy is started after the bone loss had already occurred. In the first experiment, two groups of animals were ovariectomized or sham operated, killed after 40 days, and their bones examined to ensure that bone loss occurred. In the second experiment, three groups of rats were studied. Group 1 rats were sham operated, and rats in groups 2 and 3 were ovariectomized. Each rat in group 3 received a single subcutaneous injection of 8 micrograms parathyroid hormone [hPTH-(1-34); Bachem, CA] per 100 g body weight per day, starting 40 days following ovariectomy. Rats in groups 1 and 2 received solvent vehicle, and all animals were sacrificed on day 60. Ovariectomized rats had lost an appreciable amount of bone 40 days after surgery, as indicated by a significant decrease in femoral and vertebral densities and calcium and an over 55% loss of cancellous bone in the tibial metaphysis. The loss of bone was reversed by intermittent PTH administration. Increased cancellous bone in the parathyroid hormone-treated ovariectomized rats was associated with increased trabecular osteoblasts, decreased trabecular osteoclasts, and increased serum osteocalcin and urinary hydroxyproline. Our findings indicate that parathyroid hormone can substantially augment bone mass after the loss due to ovarian hormone deficiency has already occurred. The hormone caused positive bone balance in vivo in ovarian hormone-deficient animals by increasing bone formation and decreasing bone resorption.

Animals↗
PubMed1991

A comparative study of the actions of tamoxifen, estrogen and progesterone in the ovariectomized rat.

This study was undertaken to examine the separate and combined effects of tamoxifen (T), estrogen (E2) and progesterone (P) treatment on ovariectomized (Ooph) rats. The animals were treated for 40 days. Ovariectomy reduced cancellous bone volume at the proximal tibia by 50%. Estradiol treatment completely prevented the bone loss and further increased bone volume 77% over the level for the control group. Tamoxifen also prevented the ovariectomy induced bone loss, but significantly reduced the increase in cancellous bone induced by estradiol. In the ovariectomized rats, cancellous bone apposition rate increased 23%. This increase was suppressed 63% by estradiol, and only 18% by tamoxifen. Tamoxifen significantly suppressed the inhibitory effect of estradiol on cancellous bone apposition rate. In contrast, the effect of progesterone treatment was only marginal. Our findings indicate that the action of tamoxifen on bone is influenced by the ambient level of circulating estradiol, such that in estrogen deficiency, tamoxifen has a weak estrogen agonist action on bone, and in the presence of estrogen it has anti-estrogen actions, with the dose level and mode of administration employed. These conclusions have implications for the use of tamoxifen in the treatment of pre- and postmenopausal women.

Animals↗
PubMed1991

Skeletal response of ovariectomized rats to low and high doses of 17 beta-estradiol.

Recent studies indicate that the mode of action of estrogen in preventing bone loss due to ovarian hormone deficiency may vary with the dose of the hormone. In this study four groups of ovariectomized animals were maintained on a wide range of doses of 17 beta-estradiol to further determine the relationship of dose to the mechanism by which estrogen prevents ovarian hormone deficiency bone loss. Ovariectomy caused a significant decrease in bone density and cancellous bone volume at the proximal metaphysis of the tibia. The decrease was prevented in a dose-dependent manner by estradiol. The rate of bone apposition in cancellous bone in the proximal tibia was increased by ovariectomy, and inhibited in a dose-dependent manner by estradiol. Similarly, ovariectomy increased the excretion of urinary hydroxyproline, an index of the rate of bone turnover, and serum alkaline and tartrate-resistant acid phosphatase. The increases were prevented in a dose-dependent manner by estradiol. In addition, the very high dose of estradiol, but not the lower doses, caused a marked (50%) decrease in serum osteocalcin. Our interpretation of these findings is that the low to very high doses of estradiol used in this study decreased the progression of the bone loss due to ovariectomy by suppression of the rate of bone turnover that involved the depression of both osteoclastic resorption and osteoblastic bone formation.

Animals↗
PubMed1991

The ovariectomized rat model of postmenopausal bone loss.

An animal model of postmenopausal bone loss can be defined as a living animal in which spontaneous or induced bone loss due to ovarian hormone deficiency can be studied, and in which the characteristics of the bone loss and its sequalae resemble those found in postmenopausal women in one or more respects. Although in comparison to humans, the skeletal mass of rats remains stable for a protracted period during their lifespan, rats can be ovariectomized to make them sex-hormone deficient, and to stimulate the accelerated loss of bone that occurs in women following menopause. Ovariectomy induced bone loss in the rat and postmenopausal bone loss share many similar characteristics. These include: increased rate of bone turnover with resorption exceeding formation; and initial rapid phase of bone loss followed by a much slower phase; greater loss of cancellous than cortical bone; decreased intestinal absorption of calcium; some protection against bone loss by obesity; and similar skeletal response to therapy with estrogen, tamoxifen, bisphosphonates, parathyroid hormone, calcitonin and exercise. These wide-ranging similarities are strong evidence that the ovariectomized rat bone loss model is suitable for studying problems that are relevant to postmenopausal bone loss.

Aging↗
PubMed1990

Human parathyroid hormone-(1-34) prevents bone loss and augments bone formation in sexually mature ovariectomized rats.

A group of 3-month-old Sprague-Dawley rats were sham operated or ovariectomized and given daily injections of human PTH-(1-34) (8 or 16 micrograms per 100 g body weight) for 5 weeks. At the termination of the study histomorphometric techniques were used to examine changes in cortical and cancellous bone in the diaphysis and proximal metaphysis of the tibia. Ovariectomy resulted in a 50% decrease in cancellous bone that was accompanied by a 41 and 120% increase in osteoclasts and osteoblasts, respectively. In contrast, in the ovariectomized animals treated with PTH, the metaphyseal cancellous bone increased by over 300% to a level in excess of that present in the sham-operated control animals. The increase in cancellous bone induced by PTH was associated with an over 70% increase in osteoblasts and tetracycline-labeled area and an unexpected decrease in trabecular osteoclasts. In the tibial diaphysis PTH also decreased endosteal osteoclasts and at the same time increased osteoblast size and number as well as endosteal and periosteal bone formation; ovariectomy increased only periosteal bone formation. Our findings demonstrate that intermittent administration of PTH prevents ovariectomy-induced bone loss and augments cancellous and cortical bone formation in sexually mature ovariectomized rats. Although the basis of the bone anabolic action of PTH remains elusive, our data indicate that it may involve the uncoupling of bone formation and resorption such that the latter is inhibited as bone formation is enhanced. Our findings are also compatible with the view that intermittent administration of PTH increases bone mass, in part by stimulating the proliferation and differentiation of osteoblast progenitors while inhibiting osteoclast proliferation.

Animals↗
PubMed1990

Modulation of ovariectomy-related bone loss by parathyroid hormone in rats.

Studies were carried out to examine whether parathyroid hormone (PTH) will prevent the age-related bone loss that results from ovarian hormone deficiency and to explore the mechanism of its action. Ovariectomy caused a significant decrease in bone density in the distal metaphysis and mid-diaphysis, but not in the vertebra and proximal metaphysis. The decrease was prevented by PTH injection and in all the bones examined PTH administration increased bone density and bone calcium content above the levels in sham-operated controls. Similar findings were made in bone hydroxyproline levels. PTH treated ovariectomized animals had lower serum 25(OH)vitamin D and higher 1,25(OH)2 vitamin D levels than ovariectomized and sham operated animals that received solvent vehicle. Compared to the sham operated controls, ovariectomy caused a 4.5-fold increase in the number of tartrate resistant acid phosphatase (TRAP) positive multinuclear cells. This increase did not occur in PTH-treated animals. We conclude that PTH is effective in preventing ovarian hormone deficiency bone loss in rats. PTH may mediate this effect partly by stimulating osteoblastic bone formation and partly by increasing 1,25(OH)2 vitamin D-mediated calcium absorption. The data from TRAP positive multinuclear cells indicate that an etiologic component of ovarian hormone deficiency bone loss is the expansion of a pool of osteoclast progenitors and that the bone anabolic action of PTH involves, in part, a decrease in bone resorption as a result of the suppression of the proliferation of osteoclast progenitors.

Acid Phosphatase↗
PubMed1990

Proliferation of tartrate-resistant acid phosphatase positive multinucleate cells in ovariectomized animals.

In order to explore why ovarian hormone deficiency causes excessive osteoclastic bone resorption that results in osteoporosis in a large number of postmenopausal women, bone marrow cells from ovariectomized and sham-operated female mice were cultured for 8 days. The cells gave rise in culture to tartrate-resistant acid phosphatase-positive multinucleate cells. The formation of these osteoclast-like cells was enhanced by parathyroid hormone and 1,25(OH)2vitamin D3, with the latter being more effective. Cultures of cells from ovariectomized animals formed significantly more tartrate-resistant acid phosphatase-positive multinucleate cells than those from sham-operated controls. These findings support the hypothesis that ovarian hormone deficiency promotes the expansion of a pool of marrow-derived progenitor cells that differentiate into bone-resorbing osteoclasts under the influence of osteotropic hormones.

Acid Phosphatase↗
PubMed1989

The aged rat model of ovarian hormone deficiency bone loss.

Three studies were carried out. First, the effects of aging on the maturation of the female skeleton were assessed. Second, the hypothesis that has linked ovarian hormone deficiency bone loss to hypercalcemic suppression of the parathyroids leading to a decrease in 1,25-dihydroxyvitamin D synthesis and gut absorption of calcium was examined. Third, the effects of ovariectomy and a combination of ovarian hormone deficiency and low dietary calcium on bone and the calcium-regulating hormones were evaluated. After 6 months, ovariectomy and a low calcium diet independently decreased the density of the ilium, the femur, and the fourth lumbar vertebra as well as the calcium content of the latter two. The effects of the two treatment regimens were additive and more marked in the vertebral bone. Ovariectomy lowered serum calcitonin only in animals fed a normal diet and had no effect on serum PTH and vitamin D metabolites, while a low calcium diet caused a significant increase in serum 1,25-dihydroxyvitamin D. In both dietary regimens ovariectomy resulted in about a 30% decrease in intestinal calcium absorption. A low calcium diet increased morphometric indices of bone formation and bone resorption as did ovariectomy, with resorption exceeding formation. The discussion of our findings led to the conclusion that the aged rat model of ovarian hormone deficiency bone loss qualifies for serious consideration as a practical convenient cost-effective animal model for exploring aspects of the pathogenesis and treatment of postmenopausal bone loss.

Aging↗
PubMed1988

Mechanism of dietary modulation of calcitonin levels in Fischer rats.

Aging caused an increase in serum calcitonin that was markedly suppressed by food restriction. Food restriction had no significant effect on gut calcium absorption, urinary calcium excretion, serum 1,25(OH)2 vitamin D, blood ionized calcium, the clearance of calcitonin from plasma, and its rate of inactivation in vitro by the kidney and liver. In contrast, food restriction modulated an increase with age in calcitonin secreting C-cells, thyroidal calcitonin and thyroidal calcitonin mRNA pools. We conclude that the lowering of age-related increase in serum calcitonin levels by food restriction is likely because of lowered thyroid calcitonin pools rather than changes in the metabolism of calcium, which is the primary stimulus for calcitonin secretion. Our findings also suggest that food restriction decreases age-related increase in calcitonin levels, at least in part, by modulating the expression of the calcitonin gene.

Aging↗
PubMed1988

Influence of thyroxine in the regulation of rat parotid salivary protein composition.

This study tested the role of thyroxine in the regulation of the protein composition of rat parotid saliva. Thyro-parathyroidectomy was performed on two groups of rats, one of which subsequently received thyroxine replacement; the third group was sham-operated. Parotid saliva was collected on the eighth day after surgery, with pilocarpine and isoproterenol used as a secretory stimulus. The volume of saliva collected in 30 min from the thyro-parathyroidectomized rats was 55% less than that collected from sham-operated rats. In the thyro-parathyroidectomized rats, the protein concentration as measured by absorption at 215 nm was unaltered, but that measured by the Lowry procedure was 43% higher. Spectrophotometric scans of Coomassie Blue-stained gels following sodium dodecylsulfate polyacrylamide gel electrophoresis of the secreted proteins showed an 18% reduction in the proportion of protein attributable to amylase and a 43% reduction in proportion of acidic and basic proline-rich proteins following thyro-parathyroidectomy; deoxyribonuclease and two other major secretory proteins (Fraction I and Fraction V) were increased (38%, 20%, and 46%, respectively). These changes in flow rate, protein concentration by the Lowry assay, and protein composition were prevented by treatment of thyro-parathyroidectomized rats with thyroxine replacement and are in opposition to those changes we reported earlier for hyperthyroid rats. The results indicate that the flow of saliva as well as the synthesis of the various salivary proteins are influenced by thyroxine.

Amylases↗
PubMed1988

Modulation of age-related hyperparathyroidism and senile bone loss in Fischer rats by soy protein and food restriction.

Studies were carried out to explore the influence of soy protein and food restriction on age-related changes in serum PTH and bone. Three groups of male Fischer 344 rats were studied from 6 weeks of age. Group A rats were fed ad libitum diet A, which has casein as the protein source. Group B rats were fed diet B (with casein as protein source) at 60% of the mean ad libitum food intake. Group C rats were fed ad libitum diet C, which has soy protein as the protein source. The animals were killed at periodic intervals beginning at 6 months of age after an overnight fast. Serum PTH, measured with an intact N-terminal-specific RIA, and immunoreactive calcitonin increased progressively with aging. The increase was markedly suppressed by food restriction, and in the case of PTH by the soy protein diet as well. Serum creatinine started to increase after 18 months of age, and both dietary regimens of groups 2 and 3 retarded the increase. Aging was associated with a fall in serum 25-hydroxyvitamin D, and loss of bone occurred during the terminal part of life in the ad libitum-fed animals. These were prevented by food restriction, while the soy protein diet delayed the onset of bone loss. We conclude from these findings and other data from this study that in the male F344 rats 1) an age-related increase in serum PTH precedes an age-related increase in serum creatinine concentration; 2) an age-related decline in renal function probably contributes to age-related hyperparathyroidism, which, in turn, contributes to senile bone loss; 3) food restriction inhibits age-related hyperparathyroidism and senile bone loss; 4) on the basis of the data from rats fed a soy protein-containing diet, a decline in renal function and progressive hyperparathyroidism are not inevitable consequences of aging in the ad libitum fed rats.

Aging↗
PubMed1988

The biology of aging, with particular reference to the musculoskeletal system.

A broad assessment of the current status of knowledge of biologic gerontology is presented. The extent to which the aging phenotype is due to primary aging processes, or to lifestyle, or to disease processes is discussed. Particular emphasis is placed on the aging of the musculoskeletal system. Both bone and skeletal muscle are discussed within the framework of our current knowledge of aging.

Adult↗
PubMed1987

Regulation of salivary proteins.

Previous studies have shown that several factors--such as alloxan-induced diabetes, adrenalectomy, or removal of the thyroid-parathyroid gland complex--can influence the flow rate, protein concentration, and protein composition of rat parotid saliva. The present study was undertaken to explore further the influence of glucocorticoids and thyroxine on rat parotid saliva in hormonally intact animals. As compared with untreated animals, adult male rats treated with 10 micrograms dexamethasone per 100 g body weight for eight days demonstrated a 75% reduction in volume of parotid saliva secreted in response to a uniform stimulus. The protein concentration of the saliva was increased three-fold. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed relative decreases in acidic and basic proline-rich proteins and in a protein identified as Fraction V, while amylase was increased. The electron microscopic appearance of the granules was markedly different from that of the control, in that the granules exhibited an electron-dense periphery and core, with the remainder of the granule having an electronlucent appearance. In contrast, rats treated for eight days with 20 micrograms thyroxine per 100 g body weight exhibited a 50% increase in volume of saliva collected in response to a secretory stimulus. Although the concentration of protein was not different from that of the control, gel electrophoresis showed relative increases in acidic and basic proline-rich proteins and a decrease in Fraction V. Amylase was unchanged. The secretory granules of thyroxine-treated rats were electronlucent and amorphous. The granules appeared to coalesce within the cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Evaluation of the role of calcitonin deficiency in ovariectomy-induced osteopenia.

Studies were carried out in rats to examine the role of calcitonin deficiency in the pathogenesis of ovariectomy-induced osteopenia. The parathyroid glands of 80 female Wistar rats were autotransplanted to their thigh muscle and the animals divided into 4 groups. Group 1 rats were sham ovariectomized, and thyroidectomized to make them calcitonin deficient; Group 2 rats were thyroidectomized, and ovariectomized to make them deficient in ovarian hormones as well; Group 3 rats were sham thyroidectomized and sham ovariectomized, and Group 4 rats were sham thyroidectomized and ovariectomized. A fifth group of rats were unoperated upon and served as controls. Thyroidectomized animals were maintained on thyroxine replacement and 11 months after ovariectomy all the animals were bled, killed and their femurs dissected out. In both the thyroid intact and thyroidectomized animals, ovariectomy decreased femur density significantly (P less than 0.01). Similarly, ovariectomy resulted in a decrease in femur calcium (P less than 0.01) in both groups of animals, and in a significant decrease in serum calcitonin (P less than 0.05) in the thyroid intact animals. We conclude from these findings that ovarian hormone deficiency can cause bone loss independently of lowering circulating calcitonin levels.

Animals↗
PubMed1984

Lifelong food restriction prevents senile osteopenia and hyperparathyroidism in F344 rats.

Studies were carried out on male F344 rats to examine the influence of aging and life-prolonging food restriction on bone and circulating parathyroid hormone levels. In ad libitum fed animals, the weight, density and calcium content of the femur increased with age and achieved their peak levels by 12 months of age. These levels remained stable until about 24 months and by 27 months of age the ad libitum fed animals had lost appreciable amounts of bone. The maturation of the femurs of the animals maintained on 60% of the ad libitum food intake was delayed and their bones were lighter, less dense and contained less calcium than bones from ad libitum fed rats of corresponding ages. But at 6, 12 and 24 months of age, the femur strength to body weight ratios were very highly significantly greater (P less than 0.0001) for the restricted animals compared to the ad libitum fed controls. Circulating immunoreactive parathyroid hormone increased progressively with aging in the animals fed ad libitum and the animals that experienced bone loss at advanced age also had the highest level of the hormone. In contrast, in the food restricted animals aging was not associated with a marked increase in serum parathyroid hormone or with senile bone loss. The data are discussed in relation to the mechanism of the observed changes.

Aging↗
PubMed1984

Age, strain and species differences in circulating parathyroid hormone.

A new, sensitive parathyroid hormone (PTH) radioimmunoassay that appears specific for the intact hormone, and its validation for measuring rat PTH are described. The assay is based on antibody C2-7 from chicken immunized with bovine PTH; it has a detection limit of 6 pg of bPTH per assay tube and measures basal PTH in most rats; it is responsive to provoked changes in endogenous PTH concentration, and the intra-assay and inter-assay coefficients of variation are 6.0% and 7.2%, respectively. Multiple dilutions of rat serum and parathyroid gland extract, result in competitive inhibition curves that are parallel to that of highly purified bPTH. Under our assay conditions the C2-7 antibody cross-reacts well with intact PTH but synthetic fragments of the hormone (1-34bPTH, 1-34hPTH, 28-48hPTH, 44-68hPTH, 53-84hPTH) do not depress tracer (125l-bPTH) binding to the antibody. Studies designed to validate the assay gave predictable results such as enhanced secretion of the hormone in response to EDTA infusion, and failure to detect the hormone in serum following thyroparathyroidectomy. In addition, we made the novel observation that in F344 rats circulating immunoreactive PTH increases progressively with aging.

Aging↗