Biomedical subjects

P D Broulik

Publications and source records attributed to P D Broulik.

At least 19 recordsLinked to original sources

PubMed2007

The effect of chronic nicotine administration on bone mineral content and bone strength in normal and castrated male rats.

Tobacco, containing nicotine as the principal pharmacologically active chemical, has been identified as being a risk factor for the development of osteoporosis. Thirty-two male Wistar rats of two months of age were castrated or sham operated to evaluate the effects of long-term administration (four months) of nicotine in drinking water (9.0 mg/kg/day). The presence of cotinine in urine confirmed successful delivery of nicotine. The bones were tested mechanically by a three point bending test in a Mini Bionix (MTA) testing system. The bones from castrated rats were characterized by a reduction in bone density as well as ash, calcium and phosphate content. Castration significantly altered mechanical properties of bone (9%) and femoral cortical thickness. When intact rats were treated with a high dose of nicotine, nicotine had negative effect on tibial bone density as well as ash, calcium, phosphate content and significantly altered the mechanical properties of bone (12%) and femoral cortical thickness compared to intact animals. Nicotine itself does not exert any anti-androgenic effect and does not produce changes in the weight of seminal vesicles. Nicotine-induced bone loss is associated with high bone turnover in the male rats as expressed by increased TrACP and B-ALP. When castrated rats were treated with the high dose of nicotine the changes in bone density resulting from castration were not further potentiated. These results document the efficacy of nicotine at high doses to cause bone loss and loss of bone mechanical strength in intact rats. The results of the present study may be interpreted as supporting the hypothesis of nicotine as a risk factor for osteoporosis.

Alkaline Phosphatase↗

PubMed2005

Effect of alendronate administration on bone mineral density and bone strength in castrated rats.

Castration of male rats leads to increased bone turnover and osteopenia. This study was conducted to examine the effects of the aminobisphosphonate alendronate on castration-induced bone changes. Bisphosphonates are drugs that inhibit bone turnover by decreasing the resorption. Since they suppress bone remodeling, they may also prevent the repair of microdamage and decrease bone strength. Although the mechanical properties of bones are directly related to the determination of fracture risk, bisphosphonate effects on the related variables have scarcely been investigated. Twenty-four male Wistar rats at two months of age were castrated or sham-operated to evaluate the effects of long-term administration (six months) of sodium alendronate at a dose of 1 mg/kg/day. The bones were tested mechanically by a three-point bending test in a Mini Bionix (MTS) testing system. High bone remodeling seen in castrated rats expressed by increased TrACP and B-ALP was suppressed by alendronate administration. Bone from castrated rats was characterized by a reduction in bone density as well as ash, calcium and phosphate content. Castration significantly altered mechanical properties of bone and femoral cortical thickness. When castrated rats were treated with high dose of alendronate, the changes in bone density resulting from castration were entirely prevented, and mechanical analysis revealed preserved mechanical strength of femur and cortical thickness. We conclude that castration induces cortical bone loss associated with high bone turnover in the male rat, and this bone loss can be prevented by alendronate through the inhibition of osteoclastic activity, while preserving the mechanical properties of bone. These results document the efficacy of alendronate, even at high doses, in preventing bone loss, loss of bone mechanical strength, and the rise in biochemical bone turnover indicators due to castration in rats, and raises the possibility that a alendronate could be equally effective in humans.

Acid Phosphatase↗

PubMed2003

Effects of triiodothyronine and estrogen administration on bone mass, mineral content and bone strength in male rats.

Experimental hyperthyroidism had a negative effect on bone mineral density, but did not significantly alter mechanical properties of femur and femoral bone thickness. Estradiol at a dose used in humans for the treatment of osteoporosis decreased seminal vesicle weight and concentration of testosterone but increased bone density in male rats compared to intact animals. In these rats, the mechanical analysis revealed an increased mechanical femur strength higher than the increase in bone density and femoral cortical thickness. When hyperthyroid male rats with low bone density were treated with estradiol in spite of a low plasma testosterone, the changes in bone density resulting from hyperthyroidism were entirely prevented. Estrogens protect the male skeleton against resorbing action of T (3). Treatment with estradiol in male rats with hyperthyroidism did not increase mechanical bone strength or femoral cortical thickness as it did with estradiol administration alone. Our results suggest that exogenously administered estrogens may have therapeutic value in preventing bone loss accompanying triiodothyronine administration, even in male rats with a low testosterone levels. At the concentration studied, estradiol increased in spite of low plasma testosterone, bone mineral density, mechanical strength of femur, and femoral cortical thickness.

Animals↗

PubMed2000

Tamoxifen prevents bone loss in castrated male mice.

The selective estrogen receptor modulator tamoxifen was administered to intact and castrated male mice, and its effects on tibial bones and circulatory calcium, phosphate and testosterone were compared with controls and castrated animals. Tamoxifen in a dose used in humans for treatment of breast cancer decreased the weight of seminal vesicles, an organ which is highly sensitive to the androgenic effect, decreased the concentration of testosterone, but did not have any negative effect on bone density or mineral content in intact mice. When castrated mice with extraordinarily low concentrations of testosterone and weights of seminal vesicles were treated with tamoxifen, the changes in bone density and bone mineral resulting from castration were not only entirely prevented, but increased above the values of intact mice. At the same time, cortical bone was lost in orchidectomized mice, and this decrease in cortical thickness of femur was completely prevented by tamoxifen treatment. Pharmacological therapy with estrogen agonist on bone, tamoxifen in androgen deficient adult male mice prevents bone loss.

Animals↗

PubMed1998

Beta 2-microglobulin does not behave as a biological marker of bone remodeling in patients with primary hyperparathyroidism.

Parathormone has been shown to increase the secretion and production of lysosomal enzymes including tartrate-resistant acid phosphatase. All our 68 patients with proven primary hyperparathyroidism had signs of hyperparathyroid bone disease. Tartrate-resistant acid phosphatase and bone alkaline phosphatase activities are raised as a result of enhanced bone remodelling. Serum beta 2-microglobulin concentration in patients with primary hyperparathyroidism was normal 1.6 (1.4-1.8) mg/l versus 1.8 (1.7-2.2) mg/l in 51 control subjects. In hyperparathyroid patients, serum beta 2-microglobulin concentration does not correlate with plasma tartrate-resistant acid phosphatase activity which is known to be a sensitive biological marker of bone remodelling (r = 0.088). Our findings indicate that serum beta 2-microglobulin does not behave as a biological marker of remodelling in patients with enhanced remodelling in primary hyperparathyroidism.

Adult↗

PubMed1997

Effect of antiandrogens casodex and epitestosterone on bone composition in mice.

Nonsteroidal antiandrogen casodex and steroidal antiandrogen epitestosterone were administered to intact male mice, and their effect on femoral bones and circulating calcium, phosphate, testosterone, and LH were compared with controls and castrated animals. Pure antiandrogen casodex in a dose used in humans for treatment of prostate cancer decreased the weight of seminal vesicles, organ which is highly sensitive to the androgenic effect, increased insignificantly the concentration of LH and of testosterone, but did not have any effect on bone density or mineral content of bone. Epitestosterone, which not only inhibits the binding of androgens to their receptors but also inhibits the formation of dihydrotestosterone from testosterone, and is reported to interfere with aromatization of testosterone to estrogens, decreased the bone density, ash weight, and calcium and phosphate content of femoral bone tissue significantly, although not to values as low as those seen in castrated animals.

Androgen Antagonists↗

PubMed1994

Methylene blue inhibits the stimulation of bone mass by high doses of estradiol in male rats.

To elucidate the effect of methylene blue on bone metabolism we examined the rats treated with estradiol, with methylene blue alone and with estradiol and methylene blue. The mineral bone mass in the femurs of the animals was measured quantitatively. A significant increase of bone density and bone mineral content was found in the estradiol treated animals compared to animals without estradiol. The rise in bone mineral content after estradiol was inhibited by methylene blue. Methylene blue alone did not affect bone mineral mass. From our work the possibility arose that beside well known effect of estradiol on osteoblast receptors also other mechanism of estrogen action exists which possibly may include the effect of estrogen on cytosolic guanylate cyclase producing cGMP.

Animals↗

PubMed1993

The effect of chronic nicotine administration on bone mineral content in mice.

Tobacco use has been identified as being a risk factor for the development of osteoporosis. To elucidate the effect of nicotine on bone metabolism we examined 8 intact and 8 castrated mice treated for 56 days with nicotine in drinking water and compared with the same number of mice acting as controls. The mineral bone mass in the femora of the animals was measured quantitatively. A significant reduction of bone density and bone mineral content was found in the nicotine treated animals compared to animals without nicotine. Nicotine itself does not exert any antiandrogenic effect, and it does not produce changes in the weight of seminal vesicles.

Animals↗

PubMed1993

Interrelations between body weight, cigarette smoking and spine mineral density in osteoporotic Czech women.

This study was designed to assess the influence of body weight and cigarette smoking on vertebral bone mineral density in 241 osteoporotic and age matched 98 normal Czech women. The present study demonstrated that bone density and the frequency of atraumatic vertebral fractures was not related to the body weight. High body weight was not found to show any protective action on bone. However, among a group with vertebral fractures, bone mineral density in cigarette smokers was significantly lower than in nonsmokers, but this effect was not associated with low body weight. The osteoporotic women with and without vertebral fractures had high serum cholesterol concentration which is unequivocally associated with peripheral vascular disease. Thus, our results are suggesting the relationship between atherosclerosis and osteoporosis.

Aged↗

PubMed1991

Hydrochlorothiazide inhibits parathormone-stimulated increase in plasma tartrate-resistant acid phosphatase in mice.

The inhibitory effect of hydrochlorothiazide (HTZ) on parathormone-induced bone changes in mice was studied with the aid of the analysis of plasma calcium and tartrate-resistant acid phosphatase. We have found that HTZ alone had no effect on plasma tartrate-resistant acid phosphatase (Tr-ACP), phosphate, and creatinine concentration. Parathormone (PTH) administration increased plasma Tr-ACP from 15.00 +/- 1.50 to 20.62 +/- 2.35 U/liter in intact mice. The increase of plasma Tr-ACP in HTZ-treated mice after PTH administration was not significant. The plasma calcium was affected in a way similar to Tr-ACP. HTZ reduced the sensitivity of bone to resorbing effects of PTH, using Tr-ACP as a useful biomarker of bone resorption.

Acid Phosphatase↗

PubMed1991

Calf and forearm blood flow in patients with primary hyperparathyroidism and in control subjects.

Using a venous occlusion air-filled plethysmograph we measured the blood flow in the limbs in 10 patients with established primary hyperparathyroidism and control subjects. The patients had highly raised ionized calcium and immunoreactive parathormone levels, and the diagnosis was verified at operation. In all patients resting blood flow values in the limbs were increased compared with control subjects. Peak blood flow after 5 min of ischemia was also increased, however, not significantly. This clinical study supports previous studies on a vasoactive effect of parathormone.

Adult↗

PubMed1991

Tamoxifen prevents bone loss in ovariectomized mice.

Bone density and mineral content of the femora were significantly decreased in ovariectomized mice compared with intact control animals. Tamoxifen treated ovariectomized mice did not develop any decrease either in the bone density or in calcium and phosphate content of the femora which were observed in ovariectomized mice. In addition, the weight of uterus in tamoxifen treated ovariectomized mice was the same as in intact controls. It was concluded that tamoxifen administered in vivo prevented the loss of bone mineral and uterus weight in ovariectomized mice and thus it showed a true estrogen like action in this respect.

Animals↗

PubMed1990

The tubular maximum for calcium reabsorption in patients with chronic active thoracic sarcoidosis.

The tubular maximum for calcium reabsorption (TmCa) was evaluated in 52 patients with chronic active thoracic sarcoidosis. Hypercalcaemia was found in five patients (9.6%). The mean serum calcium value of 2.54 +/- 0.18 mmol.l-1 in patients with sarcoidosis was significantly higher than that obtained in the control group (2.42 +/- 0.11 mmol.l-1). The mean TmCa in patients with sarcoidosis (2.11 +/- 0.26 mmol.l-1 glomerular filtrate (GF] was not statistically different from the mean TmCa for the group of healthy subjects (2.18 +/- 0.23 mmol.l-1 GF). Urinary sodium corrected TmCa in both groups of patients was affected in a similar way. Our study demonstrates for the first time that there is no increase in TmCa in patients with chronic active thoracic sarcoidosis. Hypercalcaemia is not a result of an increased TmCa.

Adult↗

PubMed1989

Oophorectomy did not show any additional effect on bone density and mineral content in thyroxine treated mice.

Experimental hyperthyroidism (thyroxine administration for 21 days) caused a significant decrease in ash mass, bone density and mineral content in the femora of mice, the same degree of reduction in individual measures of bone mass being found in oophorectomized and intact mice treated with thyroxine. It may be suggested that estrogens did not protect the skeleton against the resorbing action of thyroxine or triiodothyronine.

Animals↗

PubMed1988

Serum parathyroid hormone in patients with pheochromocytoma.

Studies were performed in seven unselected patients with proven pheochromocytoma pre-operatively. Serum immunoreactive parathormone and calcium levels were found to be normal in all our patients with sustained symptoms and signs of pheochromocytoma. In spite of a high circulating concentration of epinephrine or norepinephrine we did not find out any changes in serum calcium and parathormone levels.

Adrenal Gland Neoplasms↗

PubMed1988

Minoxidil does not possess androgenic activity.

Minoxidil is a potent antihypertensive vasodilator. One of the side effects of minoxidil is hirsutism. Therefore the hypothesis was tested whether minoxidil has androgenic effects. The weights of seminal mice vesicles, organs with a high sensitivity to androgens, are widely used as a sensitive bioassay for testing androgenic activity. Our results demonstrated that minoxidil in relatively high doses did not produce any significant changes in the weight of seminal vesicles of castrated mice. We conclude that minoxidil in this experimental model does not have any androgenic properties.

Androgens↗

PubMed1987

Primary hyperparathyroidism and hyperuricaemia are associated but not correlated with indicators of bone turnover.

Urate metabolism was studied in 53 patients with primary hyperparathyroidism. They had compared to controls significantly higher serum urate and reduction of the clearance of urate. In 14 of the tested patients with primary hyperparathyroidism serum urate was increased above normal limits. Six months after parathyroidectomy serum urate fell significantly from 365.3 +/- 75.7 mumol/l to 265.7 +/- 48.3 mumol/l, in 26 patients where urate measurements were available before as well as after surgery. Serum urate levels in our patients with primary hyperparathyroidism did not correlate with clearance of urate. Levels of serum urate cannot be entirely explained by the decrease in renal clearance of urate. Serum urate levels did not correlate with severity of skeletal changes expressed by serum B-ALP and urinary excretion of hydroxyproline. These results suggest that parathormone does not increase the part of the urate pool coming from the nucleic acids of the increased bone metabolism.

Adult↗

PubMed1986

Renal tubular maximum reabsorptive capacity for phosphate in patients with primary hyperparathyroidism before and after operation.

A determination was made of the renal tubular maximum reabsorptive capacity for phosphate (expressed as a function of the glomerular filtrate) in 33 patients with primary hypercalcaemic hyperparathyroidism and 30 control normal subjects. The difference between patients and controls for the maximum renal tubular reabsorptive capacity for phosphate (patients 0.526 +/- 0.16 mmol/l, controls 1.010 +/- 0.14 mmol/l) was highly significant (p less than 0.001). Successful removal of a single parathyroid adenoma in 19 patients was associated with a highly significant rise in the renal tubular maximum reabsorptive capacity for phosphate (1.005 +/- 0.21 mmol/l, p less than 0.001). We did not find any correlation between the renal tubular maximum reabsorptive capacity for phosphate and serum immunoreactive PTH level. Low renal tubular maximum reabsorptive capacity for phosphate in the presence of hypercalcaemia is highly suggestive of primary hyperparathyroidism.

Absorption↗