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Biomedical subjects

P F Hirsch

Publications and source records attributed to P F Hirsch.

At least 19 recordsLinked to original sources
PubMed1991

Lower serum osteocalcin in ethanol-fed rats.

Serum osteocalcin was remarkably and significantly (-34 and -41% in two separate experiments; p less than 0.001) lower in rats fed an 8% (w/v) ethanol liquid diet (ELD) for 1 week than in rats fed an isocaloric control liquid diet (CLD). In a longer experiment that spanned 4 weeks, the ELD rats were given 6% ethanol on day 4, increased stepwise to 8% by day 9, and then maintained at 8% until day 28, when the experiment was terminated. Again, serum osteocalcin was much lower (-32%, p less than 0.001) in the ELD-fed rats than in CLD-fed rats. Even in rats fed only a 6% ELD for 12 days, serum osteocalcin was lower (-33%, p less than 0.001) than in controls. Also, the femora were weaker, more compliant, and more ductile in ELD-than in CLD-fed rats, findings that confirmed our earlier, related work. The fall in serum osteocalcin in ELD-fed rats is associated with a fall in femur ash weight and bone strength. There were significant correlations between serum osteocalcin and bone strength (r = 0.80; p less than 0.001) and between serum osteocalcin and bone stiffness (r = 0.83; p less than 0.001). Serum ionized calcium, like osteocalcin, was consistently lower in rats given ethanol for 1 or 4 weeks than in controls. From these experiments we conclude that excessive ethanol consumption inhibits osteoblastic activity as indicated by the reduced serum osteocalcin. The inhibition is also associated with other deleterious effects of ethanol on bone, including ash weight, bone strength, and bone stiffness.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Hypocalcemic effect of physiological concentrations of corticosterone in adrenalectomized-parathyroidectomized rats.

We have confirmed the serum calcium-raising effect of adrenalectomy in young male rats 5-6 h after parathyroidectomy that was first observed by others many years ago. (The phenomenon has also been reported in cats, dogs, and mice.) In addition, we have shown that adrenalectomy raises the serum ionized calcium as well as total calcium and that the effect occurs in young female as well as in young male rats. Furthermore, we have found that the serum calcium-raising effect of adrenalectomy occurs if the adrenalectomy is performed several days before parathyroidectomy or 6 h after parathyroidectomy, as well as at the same time as the parathyroidectomy. When the rats were adrenalectomized 7-9 days before parathyroidectomy and given small daily life-maintaining doses of corticosterone or cortisone acetate, this glucocorticoid treatment did not reverse the adrenalectomy effect. This led us to think at first that the effect of adrenalectomy must be due to the loss of an unknown adrenal factor rather than to loss of glucocorticoid. Additional experiments, however, in which corticosterone or hydrocortisone was administered by continuous release pellets, demonstrated conclusively that a small continuous supply of corticosterone (within the physiological range as determined by immunoassay of plasma) was sufficient to reverse the adrenalectomy effect. The results with hydrocortisone were similar at even lower doses than of corticosterone. Somewhat higher doses of corticosterone or hydrocortisone reduced the serum calcium even below the parathyroidectomy level. In a preliminary investigation of the specificity of the glucocorticoid effect we found that aldosterone, dehydroepiandrosterone, or estradiol had no effect on serum calcium under similar conditions. We conclude that the fall in serum calcium after parathyroidectomy in rats is due in part to the hypocalcemic effect of endogenous corticosterone. Thus, the loss of corticosterone after adrenalectomy explains the serum calcium-raising effect of adrenalectomy in parathyroidectomized rats. These results also suggest that glucocorticoids at physiological levels have a significant effect on calcium metabolism in general.

Adrenalectomy↗
PubMed1990

A scanning electron microscopic and photon absorptiometric study of the development, prolongation, and pattern of recovery from lactation-induced osteopenia in rats.

Measurements by scanning electron microscopy (SEM) of femoral hemisections confirmed and amplified results by single-photon absorptiometry that had shown a marked increase in lactation osteopenia in rats fed a low-calcium diet (LCD, 0.04% Ca) as compared with a medium-(adequate) calcium diet (ACD, 0.4% Ca). SEM of bones from rats at the end of lactation on either diet showed a large loss of trabecular bone, increased porosity of endosteal surfaces, and cortical thinning. These changes were much more striking in LCD rats than in ACD rats. Backscattered electron imaging of cross sections of the femora revealed marked cortical thinning at midshaft after lactation, especially in rats on the LCD; this method also showed a marked increase in newly formed, less dense diaphyseal bone on the endosteal surface when dietary calcium had been made available to the LCD rats after lactation ceased. Unlike the rats fed the ACD after lactation, the rats continued on the LCD for the first 3 weeks postlactation failed to recover bone mineral, even though there was a marked decrease in resorbing surfaces of the femora as revealed by morphologic examination. When the diet was changed from the LCD to the ACD for the second 3 weeks postlactation (week 4-6), the bone mineral increased substantially. Overall, these results demonstrate the marked loss of bone during lactation, especially severe in rats fed a low-calcium diet, and the rapid postlactational recovery of bone when adequate dietary calcium was made available, even if the recovery had been delayed for the first 3 weeks by feeding a diet very low in calcium.

Absorptiometry, Photon↗
PubMed1989

Influence of ethanol on stiffness, toughness, and ductility of femurs of rats.

Recently, we reported that the ingestion of alcohol in rats reduced the mechanical strength of femurs. Our results showed that, as the dose exceeded 0.012 g of ethanol per gram of body weight, a significant (p less than 0.001) loss of "strength" occurred that was independent of sex according to the relationship, Strength (N) = 140.4 - 6003 dose (g/g). In the present effort, the same flexure tests were reevaluated to include the parameters of stiffness, toughness, and ductility. These latest results confirm that the femurs of rats fed an ethanol liquid diet for 4 weeks are not only weaker but also more compliant and less energy absorbing. Although the femurs of rats fed ethanol are more ductile, the bones are more prone to fracture in fatigue and impact circumstances as well as under simple loading situations. The rat may be an appropriate model to study the mechanisms that lead to the higher incidence of fractures in the alcoholic human.

Animals↗
PubMed1988

Ethanol-induced changes in morphology and strength of femurs of rats.

Chronic ingestion of ethanol resulted in ultrastructural and mechanical changes in rat femurs. Scanning electron microscopy of the distal end of the femur revealed that the trabeculae of bones from ethanol-fed rats were thinner, more columnar, and more extensive than those from control rats. Three-point bending tests of the rat femurs showed that the maximum force or so-called "strength" required to break the bone was less in ethanol- than in control-fed animals. A significant inverse correlation was observed between the strength required to break the femur and the dose of ethanol calculated on a body weight basis. For the first time our study presents quantitative proof that a relationship exists between bone strength and the consumption of ethanol in rats. The study revealed that ethanol consumption resulted in a weaker femur compared to controls. We suggest that a common mechanism may be responsible for the decreased bone strength of ethanol-fed rats and the increased incidence of fractures in human alcoholics.

Alcoholism↗
PubMed1988

Effect of number of suckling pups and dietary calcium on bone mineral content and mechanical properties of femurs of lactating rats.

The bone loss that occurs during lactation in rats was aggravated by increasing the number of suckling pups and was further accentuated by feeding the rats a calcium (Ca)-deficient diet. The bone loss was evenly distributed along the whole length of the femur in severe cases. In less severe cases, the metaphyses were affected more than the midshaft. Mechanical properties of femurs, i.e., bone 'strength', 'stiffness', 'toughness' and 'ductility', were all affected in lactating rats suckling seven to eleven pups and fed the 0.1% Ca diet. The positive correlation between bone 'strength' and ash weight is consistent with the concept that when there is loss of bone, bone becomes more susceptible to fracture. The fall in serum ionized Ca and the rise in serum iPTH were closely related to the intensity of lactation and were profoundly affected by litter size and Ca concentration of the diet. We conclude that the change in Ca homeostasis in lactating rats is due to the large loss of Ca required for milk production and that the loss of Ca is associated with hyperfunction of the parathyroid gland. Furthermore, a Ca-deficient diet severely reduced bone mineral content and affected the mechanical properties of femurs of lactating rats adversely, especially those suckling large litters of pups.

Animals↗
PubMed1987

Influence of lactation and pregnancy + lactation on mechanical properties and mineral content of the rat femur.

The quality of bone was assessed from femurs of rats both during lactation and after pregnancy + lactation. Mechanical properties of stiffness, strength, toughness, and ductility were measured, along with standard measurements of dry weight, ash weight, and total bone mineral. No changes occurred during the first week of lactation. During the second and third weeks of lactation all bone parameters except ductility decreased significantly. These data are consistent with bone losing mineral in order to supplement the dietary calcium intake necessary for milk production. In other experiments, femurs were collected from nulliparous rats and from rats that had previously undergone 1-3 pregnancy + lactations. The largest changes in bone mineral and mechanical properties occurred after a single pregnancy + lactation period, although significant further decreases in stiffness and strength occurred after the second pregnancy + lactation. No additional losses occurred following the third pregnancy + lactation. Even 5 months after only one pregnancy + lactation period, the bone quality was still impaired as all bone properties were lower than in nulliparous controls. Because the changes, especially stiffness and strength, were relatively larger than the changes in dry and ash weights of bone, measurements of these mechanical properties provide a more sensitive method to evaluate the quality of bone.

Animals↗
PubMed1987

Increase in serum parathyroid hormone concentration in the lactating rat: effects of dietary calcium and lactational intensity.

The change in circulating levels of immunoreactive parathyroid hormone (iPTH), measured with an N-terminal specific radioimmunoassay, was examined during lactation in rats. In lactating rats consuming a diet containing 0.4% Ca (basic diet), serum iPTH was a) increased by an average of 53% between days 10 and 18 compared to the level of age-matched nonlactating rats (24.7 +/- 2.1 pg/ml vs 16.1 +/- 0.8 pg/ml, mean +/- SE, p less than 0.01) and b) significantly higher in dams suckling large litters (10-15 pups) than in dams suckling small litters (3 pups) over the period 3-13 days of lactation. Lactating rats consuming a low calcium diet (0.04% Ca), had serum iPTH levels on days 16-18 of lactation approximately twice those of nonlactating rats fed the same diet and 73% higher than those of lactating rats fed the basic diet. Serum Ca concentrations were 22% and 10% lower in dams consuming the 0.04 and 0.4% Ca diets, respectively, than in the nonlactating controls fed the same diets. Regression analysis showed a significant (p less than 0.001) negative correlation between iPTH and total serum calcium. Compared with nonmated controls, net mineral loss from femurs of dams consuming the 0.4% Ca diet was a) insignificant at day 6, b) 27% at day 15, and c) 34% at day 21 of lactation. Our data demonstrate that lactation in the rat is characterized by hyperparathyroidism that appears to be related to lactational intensity and that is accentuated when dietary calcium intake is restricted.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Interrelationships of bone ash and whole bone properties in the lactating and parous rat.

Several investigators have studied the mechanical properties of long bones of rats and have found that bone strength may be associated with bone mineral content. In this study we examined further the interrelationships of whole bone properties and bone ash weight of the rat femur. Using a 3-point bending test, the bones were evaluated during lactation and after one to three pregnancy + lactation periods--experiments in which bone ash was significantly reduced. A relationship was established between the time of lactation and the ash weight, stiffness, strength, and toughness but not the ductility. Using all of the experimental data, a highly significant relationship was observed between ash weight and stiffness. A similar significant correlation was revealed between bone ash and strength or toughness, although drawing individual lines for each experiment rather than a common line for all the experiments appeared more appropriate. Given the inherent inaccuracies in the material property measurements of bone, the results suggest that routine measurements of whole bone properties provide an important and sensitive way to evaluate bone quality and that these properties correlate significantly with the bone ash weight.

Animals↗
PubMed1986

Reduced bone mass in calcitonin-deficient rats whether lactating or not.

Calcitonin deficiency was produced in lactating and age-matched nonmated rats by thyroidectomy (TX) after transplantation of the parathyroid glands to a thigh muscle. At the end of lactation and a comparable period in the nonlactating rats, this condition resulted in femurs, vertebrae, and tibiae that weighed less than those in the thyroid-intact controls. Furthermore, the femurs of the CT-deficient rats were narrower at midshaft and shorter, indicating reduced bone growth. The reduction in bone mass in CT-deficient rats, although highly significant, was much smaller than that caused by lactation. Adequate thyroid hormone replacement therapy was provided by giving all the TX rats L-thyroxine (T4) sc or in the drinking water. The body weights of the lactating rats were heavier than those of their nonmated controls but TX had no significant effect on the mean body weight of either group. The previously observed lower concentration of serum calcium in lactating rats than in nonlactating thyroid-intact rats was also seen in TX rats, indicating that CT is not responsible for the relatively low serum calcium during lactation. Our results showing that the bones of TX rats (with T4 replacement) were smaller and lighter than those from thyroid-intact controls whether lactating or not do not support the concept that CT has a special physiological function to protect the skeleton during lactation.

Animals↗
PubMed1986

Cytochemical bioassay of circulating concentrations of rat parathyroid hormone: application to a study of age and sex.

We have found that the cytochemical bioassay (CBA) method, originally developed to measure circulating levels of biologically active parathyroid hormone (bioPTH) in humans, also can measure endogenous concentrations of PTH in rats. Therefore, we have applied this assay method to examine the relationships between age and sex and the circulating levels of bioPTH, calcium, and phosphorus in Fischer rats. The concentration of bioPTH increased in both males and females from 5 to 15 months of age (p less than .001) with no significant sex-related difference. Mean bioPTH values ranged from 2.3 to 3.6 pg (human PTH equivalents)/ml; these values were much lower (1 to 2 orders-of-magnitude) than those reported by others who used radioimmunoassays for PTH that do not discriminate between biologically active and inert PTH fragments. The CBA values for bioPTH were also 1/4-1/5 those obtained in rat serum by newer, more sensitive methods, the N-terminal specific PTH radioimmunoassay and the bioassay based on stimulation of chick renal adenylate cyclase. Regression analysis did not reveal any significant correlation between serum calcium and age. However, serum inorganic phosphorus decreased significantly (p less than .001) from 5 to 15 months of age in both male and female rats and was much lower in females than in males (p less than .001). The fall in serum phosphorus was negatively correlated with the rise in bioPTH (p less than .001). This study, the first to our knowledge to use a CBA to detect physiological changes in the circulating levels of bioPTH in rats, demonstrates the usefulness of the assay in experiments in this species.

Aging↗
PubMed1975

Purification, characterization and radioimmunoassay of thyrocalcitonin from rat thyroid glands.

A highly purified preparation of rat thyrocalcitonin (TCT) has been obtained from lyophilized thyroid glands by gel chromatography following acid-acetone extraction. Biological activity of Sephadex G-50 eluates appeared in two peaks. The TCT in the major peak was concentrated, and applied to a Bio-Gel P-6 column, and a major protein peak was eluted which coincided with TCT activity. Potency, estimated by bioassay in rats, increase approximately 3500-fold from 0.075 MRC U/mg lyophilized glands to 250-400 MRC U/mg in the final product. The overall yield of TCT activity was about 36%. The purified product was characterized by chemical procedures and evaluated for its antigenic properties and use for radioimmunoassay. The purified rat TCT was used both labeled with 125I and as unlabeled standard. The following results were obtained: 1) Guinea pig antisera to either human or rat TCT were capable of binding 125I-rat TCT or 125I-human TCT; 2) Using either 125I-human or 125I-rat TCT and antisera to either TCT, pg amounts of rat and human TCT reacted in the assay while ng to mug amounts of salmon calcitonin or porcine TCT failed to react; 3) Using 125I-rat TCT and antisera to human or rat TCT, synthetic C-terminal (10-32 or 22-32) fragments of human TCT reacted well, while N-terminal (1-18) or desamide (1-32) derivatives reacted poorly or not at all; 4) Rat TCT was easily detected in normal thyroid venous plasma (5-10 ng/ml) and thyroid gland extracts (similar to 1 mug/gland) but not in peripheral blood; 5) Bioassay and radioimmunoassay of rat thyroid extracts (N equals 18) showed good agreement (r equals 0.86, p less than 0.001). The results support the idea that rat TCT is closely related to human TCT, indicate that major antigenic determinants reside in the C-terminal portion of the molecule, and show that antisera to either human or rat TCT can be used to measure rat TCT.

Amino Acids↗