PubMed Health⌕ Search

Biomedical subjects

P Lakatos

Publications and source records attributed to P Lakatos.

At least 19 recordsLinked to original sources
PubMed1995

Endothelin receptors, second messengers, and actions in bone.

Endothelins are a class of peptides that are produced by and elicit responses in many tissues. A growing literature documents the presence and effects of endothelins in bone. Both endothelinA and endothelinB receptors have been demonstrated in osteoblastic cells by ligand binding. Major signal transduction pathways for endothelin in bone cells appear to be stimulation of phospholipid turnover, by activation of A, C and D phospholipases, stimulation of calcium flux from intracellular and extracellular stores and activation of tyrosine kinases. Endothelins also modulate calcium signaling elicited by other agents in osteoblastic cells. The parathyroid hormone-stimulated calcium transient in UMR-106 cells is enhanced by endothelins, acting through an endothelinB receptor, whereas the parathyroid hormone-stimulated increase in cyclic AMP is inhibited by endothelins. Phenotypic responses to endothelin-1 include changes in alkaline phosphatase activity, stimulation of osteocalcin and osteopontin message, stimulation of collagen and noncollagenous protein synthesis, inhibition of osteoclast motility and stimulation of prostaglandin-dependent resorption. Endothelin-1 also enhances the interleukin-1-induced increase in interleukin-6. Endothelins can also potentially affect calcium metabolism through their actions to inhibit the secretion of parathyroid hormone.

Animals↗
PubMed1995

Circadian rhythm of in vitro bone-resorbing activity in human serum.

Calciotropic hormones as well as biochemical parameters of bone formation and resorption show circadian rhythms. In a previous study in the rat, we observed a circadian rhythm in serum bone-resorbing activity (SBRA). In the present study, we investigated whether there was a circadian rhythm of SBRA in human serum. For this purpose, we studied 10 healthy premenopausal women and 5 healthy men. Blood was collected every 2 h, and urine samples were collected during 4-h periods for 24 h. For the determination of SBRA, media were prepared by reconstituting serum samples with Dulbecco's Modified Eagle's Medium at a ratio of 20% serum and 80% Dulbecco's Modified Eagle's Medium. Limb bones were dissected from 19-day old fetal rats prelabelled with 45Ca and were cultured for 72 h in the presence of the sera. Bone resorption was assessed from the 45Ca released into the culture medium and from that retained in the bone and was expressed as percentage 45Ca release. Serum calcium, phosphorus, PTH, cortisol, and urinary pyridinium cross-links were also determined. SBRA in human serum followed a circadian rhythm with a peak at about 0300 h and a nadir at 0700 h. There was no significant difference between the rhythm of SBRA of women and men. At concurrent time points, SBRA and serum PTH were positively correlated (r = 0.629; P < 0.01), and SBRA and serum cortisol were negatively correlated (r = 0.797; P < 0.01). To further investigate the possible contribution of these hormones to SBRA, either neutralizing anti-PTH antibody or RU-486 (mifepristone), a glucocorticoid receptor antagonist, was added to the serum samples of 6 subjects. Neutralizing the effect of PTH did not change the pattern of SBRA rhythm. The addition of RU-486 had a significant effect on the rhythm of SBRA, reducing the peak and nadir amplitudes. Thus we conclude that cortisol plays a major role in the rhythm of SBRA present in human serum; however, the influence of other factors cannot be excluded. Cortisol may be an important determinant of the circadian rhythm of bone resorption in vivo.

Adult↗
PubMed1992

[Spinal and appendicular osteoporosis in streak gonad syndrome. Photon absorptiometric and roentgen-morphometric studies].

Patterns of bone loss in the axial and the appendicular skeleton were studied in 48 women with streak gonad syndrome (age: between 14-38 years, mean: 25.5 years). Bone mineral content was measured in vivo at the lumbar spine and right femoral neck by dual photon absorptiometry and at the midradius and distal radius by single photon absorptiometry. The bone mineral status of 20 patients was evaluated by radiomorphometrical indices of the metacarpals, femorals and lumbar spine, too. Mean bone mineral content and radiomorphometrical indices were significantly lower in patients with streak gonad syndrome than in age-matched normal subjects at all three scanning sites. The patients lost cortical and trabecular bone mineral content at the same rate, suggesting that bone loss in streak gonad syndrome is a generalized phenomenon. In spite of serious bone loss osteoporotic fractures were not observed in the patients, in contrast to patients with pathological post-menopausal osteoporosis having equal degree of bone deficiency. The authors did not find any relationship between the occurrence of osteoporosis and the karyotype of the patients. It is suggested that the osteoporosis in streak gonad syndrome--at least after puberty--is a consequence of gonadal hormone deficiency.

Absorptiometry, Photon↗
PubMed1992

Effects of endothelin-1 on signal transduction in UMR-106 osteoblastic cells.

Endothelin-1 is now recognized to affect the functions of a number of tissues and to activate calcium/phospholipid second messenger pathways in target cells. In the present study, we characterized its effects on signal transduction in UMR-106 cells. To study calcium transients elicited by endothelin-1, cells were loaded either with fluo-3 (for the measurement of cytosolic free calcium) or chlortetracycline (for the measurement of intracellularly stored calcium) as fluorescent probes. Intracellular production of inositol phosphates and cyclic AMP was also measured. Endothelin-1 elicited dose-dependent cytosolic calcium transients with an ED50 of 20 nM. This effect was also seen in EGTA-containing or calcium-free medium; however, the signals were reduced in magnitude. The dihydropyridine calcium channel antagonist nifedipine did not affect the response. Repeated administration of endothelin-1 resulted in homologous desensitization of the response. A 4 minute pretreatment with phorbol ester reduced the initial response to endothelin-1 in both calcium-containing and calcium-free media. A 24 h pretreatment with indomethacin had no effect on response. Using chlortetracycline as an indicator, a significant reduction in intracellularly stored calcium by endothelin-1 was observed. This was prevented by 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate, a blocker of calcium release from internal stores. Endothelin-1 also stimulated the dose-dependent production of inositol phosphates by UMR-106 cells. Indomethacin was also without effect on this process. The increase in inositol trisphosphates was seen within the same time frame as the increase in cytosolic calcium. Endothelin-1 did not influence cyclic AMP production over 5 minutes in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗
PubMed1992

Effects of cyclosporins and transforming growth factor beta 1 on thyroid hormone action in cultured fetal rat limb bones.

To study the mechanism of action of thyroid hormones on bone, we examined the effects of immunosuppressive and nonimmunosuppressive cyclosporins, as well as of transforming growth factor beta 1 (TGF beta 1), 17 beta-estradiol (E2), and dihydroxytestosterone (DHT) on thyroxine (T4)- and triiodothyronine (T3)-stimulated bone resorption in fetal rat limb bones. The immunosuppressive cyclosporins A (CsA) and G (CsG) inhibited thyroid hormone (T4 + T3)-stimulated resorption and beta-glucuronidase release into the culture medium, whereas the weak or nonimmunosuppressive cyclosporins D (CsD) and H (CsH) did not show this effect. Increasing the medium calcium concentration reduced the ability of T4 to stimulate 45Ca release, while not significantly affecting the response to CsA. TGF beta 1 elicited a biphasic effect when administered together with T4. During the first 3 days of culture, TGF beta 1 elicited a small, nonsignificant decrease in released 45Ca; during a subsequent 3 days of culture, it enhanced T4-stimulated bone resorption significantly. These effects differed from those of TGF beta 1 on parathormone-stimulated resorption. E2 and DHT did not influence the action of T4 on bone tissue. These results suggest that the mechanism of action of thyroid hormones on bone may involve immune factors, as well.

Animals↗
PubMed1992

Effects of gallium nitrate on calcium transients in UMR-106 rat osteoblastic osteosarcoma cells.

Gallium nitrate is an effective antihypercalcemic and antiresorptive agent. Although its effects on osteoclasts are well documented, the mechanism of action of gallium nitrate on osteoblasts is still not established. To determine the effects of gallium nitrate on calcium signalling, we studied its effects on intracellular calcium concentration in UMR-106 rat osteoblastic osteosarcoma cell line. Cells were loaded with a calcium binding fluorescent dye, fluo-3. Changes in fluorescence reflected changes in cytosolic calcium. Gallium nitrate elicited a dose-dependent biphasic calcium transient with an initial decrease followed by an increase, and these changes were seen at high extracellular calcium concentration. Markedly altered signal was seen in nominal calcium-free medium, suggesting that gallium nitrate mobilized calcium only partly from intracellular stores. Gallium nitrate, at concentrations as low as 3 micrograms/ml, inhibited parathyroid hormone-stimulated calcium transients. High doses of parathyroid hormone could overcome this inhibition. This inhibitory effect appears to be selective, since gallium nitrate did not prevent calcium transients elicited by alpha-thrombin or prostaglandin F1 alpha. Failure of gallium nitrate to prevent calcium transients elicited by these agents, even after the inhibition of parathyroid hormone-induced signal, indicates that the inhibition is not a toxic effect. In conclusion, gallium nitrate has a marked effect on calcium signalling in UMR-106 cells that might be of major importance in modifying the effects of calcemic hormones or local factors on osteoblasts.

Animals↗
PubMed1992

Endothelin-1 actions on resorption, collagen and noncollagen protein synthesis, and phosphatidylinositol turnover in bone organ cultures.

The effects of endothelin-1 (ET) on several tissues are mediated by prostaglandins. In this study, we investigated the actions of ET on bone and determined whether they are mediated through prostaglandin-dependent pathways. Bone resorption, collagen, and non-collagen protein synthesis and inositol phosphate (IP) production were studied in neonatal mouse calvaria and fetal rat limb bone cultures. The effects of ET in the calvaria model were examined in the presence or absence of the cyclooxygenase inhibitor indomethacin (INDO). Bone resorption was stimulated by ET in the neonatal mouse calvaria, and this effect was inhibited by INDO. 45Ca release in the fetal rat limb bones was not affected by ET. ET stimulated collagen and noncollagen protein synthesis significantly in the calvaria model in the presence but not in the absence of INDO, suggesting that the anabolic effects of ET were masked by endogenous prostaglandin production. ET increased phosphatidylinositol turnover in both bone organ cultures. Although the addition of INDO reduced IP production slightly in the mouse calvaria, it was still significantly stimulated by ET. Our results demonstrate that ET has marked effects on bone tissue in vitro. Effects on resorption appear to be prostaglandin dependent, whereas the anabolic effects were not prostaglandin mediated. The stimulatory effects of ET on protein synthesis could be mediated through the IP signaling pathway. Since ET stimulates both bone resorption and anabolism, this peptide may have a role in the coupling of bone remodeling.

Animals↗
PubMed1991

[Decreased serum osteocalcin level in non-alcoholic and alcoholic chronic liver diseases].

Serum level of osteocalcin (OC) is believed to be a specific biochemical parameter of bone formation. Decreased serum OC has been reported in alcohol-intoxicated subjects, in patients with primary biliary cirrhosis and in patients with chronic alcoholic liver disease. The question was, whether lower OC level could be detected in patients with nonalcoholic and non-cholestatic chronic liver disease. The serum OC was measured by RIA developed in our laboratory. Results were compared to age and sex matched controls. Decreased OC level was found in 35 out of 47 (74%) patients with non-alcoholic and non-cholestatic liver disease as chronic persistent hepatitis, chronic active hepatitis, fatty liver and cirrhosis, in 21 out of 26 (80%) patients with alcoholic liver disease and in 8 out of 15 (53%) primary biliary cirrhosis. None of the patients had elevated value. There was no correlation between the decreased OC level and the duration or severity of the liver disease and the laboratory parameters as bilirubin, AST, ALT, alkaline phosphatase, albumin, prothrombin, and serum 25-OH-D3 vitamin level. Decreased OC was found also in the patients without cirrhosis. The possible causes are discussed. Relying upon these findings it is supposed that chronic liver disease by itself can influence the osteoblast activity also by some unknown mechanism.

Bone Diseases, Metabolic↗
PubMed1991

Gallium nitrate inhibits bone resorption and collagen synthesis in neonatal mouse calvariae.

Gallium nitrate (GN) is an agent used in the treatment of hypercalcemia. To more fully characterize the direct actions of GN on bone, we examined its effects on medium calcium, medium beta-glucuronidase (beta-GLU), and collagen synthesis in control and hormone-stimulated neonatal (4-6 days) mouse calvariae in vitro. GN (10 micrograms/ml) inhibited parathyroid hormone-stimulated (PTH; 1 nM) calcium release. A 24 h preincubation with 10 micrograms/ml of GN was required for complete inhibition; partial inhibition was seen with 12 h preincubation; 1, 3, or 6 h was inadequate. A dose-response study showed that with 24 h preincubation, 5, 3, and 1 microgram/ml of GN inhibited 81, 62, and 0% of PTH-induced calcium release. The effects of GN on the release of beta-GLU generally paralleled those on the release of calcium except that 10 micrograms/ml of GN stimulated beta-GLU release. Collagen synthesis was inhibited 50% by 3 micrograms/ml of GN, whereas noncollagen protein synthesis was unaffected. With PTH + GN no further decrease was observed. When GN was withdrawn from the medium after 24 h of preincubation, the inhibitory effect on calcium release and beta-GLU activity, but not on collagen synthesis, persisted through the 72 h of culture. GN also inhibited the resorption elicited by thyroxine (1 microM) and interleukin-1 beta (10 nM) but not by 1,25-dihydroxyvitamin D3 (30 pM). Our results indicate that GN is a powerful inhibitor of bone resorption in neonatal mouse calvariae even at low doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Serum bone Gla protein in streak gonad syndrome.

Osteoporosis is one of the most common complications of streak gonad syndrome (SGS), however its pathogenesis is still unclear. Bone Gla protein (BGP) has been found to be a serum marker of bone turnover in various metabolic disease states. In the present study serum BGP and alkaline phosphatase (AP) were measured in 13 osteoporotic patients with SGS and in 56 healthy women. Mean (+/- SD) serum BGP levels were normal (7.5 +/- 2.0 ng/ml) in seven patients who had been on estrogen-progestin replacement therapy and became significantly elevated (P less than 0.001) 2 and 3 months after discontinuation of the treatment (15.3 +/- 2.3 and 13.2 +/- 1.0 ng/ml, respectively). Mean (+/- SD) serum AP (207 +/- 65 U/l) showed significant increases (P less than 0.05) 2 months after withdrawal of hormonal substitution (287 +/- 74 U/l). Mean (+/- SD) serum BGP (15.4 +/- 3.5) and AP (287 +/- 49) levels were significantly higher (P less than 0.001 and less than 0.05, respectively) in six patients with SGS who had not been on hormonal substitution. These findings are consistent with those obtained in postmenopausal women suffering from "high remodelling osteoporosis" and suggest that bone turnover in osteoporotic patients with SGS is increased and the skeletal loss is a consequence of accelerated bone loss rather than decreased bone formation.

Adult↗
PubMed1991

Evidence for direct non-genomic effects of triiodothyronine on bone rudiments in rats: stimulation of the inositol phosphate second messenger system.

Thyroid hormones increase cytosolic free calcium by binding to plasma membrane receptors in several tissues. This calcium increase appears to initiate extranuclear effects in these tissues. Increases in cytosolic calcium are often a consequence of stimulation of inositol phosphate second messenger pathway. Several calcemic hormones act via this signal transduction route. Therefore we investigated the effects of the metabolically active T3 and the inactive analogues 3,5-diiodotyrosine and rT3 on the inositol phosphate pathway in fetal rat limb bone cultures prelabeled with [3H]myoinositol. Labelled inositol and inositol phosphates were separated by HPLC. There was a significant increase in the radioactivity in inositol bis- and trisphosphates after 1 min of exposure to 10(-7) mol/l T3. Stimulation was also observed at 10(-6) mol/l T3, but not at 10(-5) mol/l. Time course studies demonstrated a rapid effect of T3 on inositol phosphates within 30 seconds that lasted through 5 min. After 20 min incubation with T3, no increase was observed in inositol mono- and bisphosphates, and a decrease was seen in inositol trisphosphate. Pretreatment with indomethacin prevented these effects of T3. 3,5-diiodotyrosine and rT3 did not affect inositol phosphate metabolism. These results suggest the existence of plasma membrane-associated receptors for T3 in bone, in addition to the nuclear receptors demonstrated previously. The role of these receptors in the effects of thyroid hormones on bone remains to be established.

Animals↗
PubMed1990

[Serum sex hormone-binding globulin levels in thyroid diseases].

Synthesis of "sex-hormone binding globulin" is influenced by the thyroid hormones and its concentration in the serum may be a marker of the thyroid hormone effect at the peripheral tissue (liver) level. Compared to euthyroid controls serum "sex-hormone binding globulin" concentration is elevated in overt hyperthyroidism (141.6 +/- 37.6 vs 48.3 +/- 16.2 nmol/l; p less than 0.001), conversely, its mean level is decreased in the hypothyroid group of patients (24.9 +/- 14.8 vs 48.3 +/- 16.2; p less than 0.001). In the group of subclinical hyperthyroidism the mean value of "sex-hormone binding globulin" corresponds to that in control subjects (47.4 +/- 16.8), while its serum level is near the lower border of the normal range in subclinical hypothyroidism (33.6 +/- 6.1 vs 48.3 +/- 16.2; p less than 0.01). During thyroid hormone replacement for hypothyroidism measurement of serum "sex-hormone binding globulin" may help to assess the response of the target organs to the hormone therapy. In patients with peripheral thyroid hormone resistance serum "sex-hormone binding globulin" level is within the normal range (51.3 +/- 9.8), its determination supports the diagnosis of this disease.

Adult↗
PubMed1990

[Serum osteocalcin levels in healthy males and females in relation to age].

The measurement of serum osteocalcin is a new sensitive and specific method in the evaluation of calcium metabolism disorders. We established the normal values of healthy adult Hungarian women (n = 111, age: 20-86 yrs, mean: 47 yrs) and men (n = 70, age: 20-88 yrs, mean: 42 yrs) by radioimmunoassay method developed at our institute. Serum osteocalcin levels are constant between 20-50 yrs (7,8 +/- 2,4 ng/ml) while the values are significantly higher after 50 yrs of age (11,0 +/- 4,6 ng/ml) and remain constant afterwards. A correlation might be supposed between this elevation around 50 and bone loss around menopause. Serum osteocalcin values of men are constant with aging (11,0 +/- 3,9 ng/ml).

Age Factors↗
PubMed1990

The measurement of the serum sex-hormone binding globulin in various thyroid diseases.

Synthesis of "sex-hormone binding globulin" (SHBG) is influenced by thyroid hormones and its concentration in the serum of female subjects may be a marker of thyroid hormone effect at the peripheral tissue (liver) level. Compared to the levels found in euthyroid females (n = 46), the mean (+/- S.D.) serum SHBG concentration was found elevated in overt hyperthyroidism (Graves' disease: n = 56; 141.6 +/- 37.6 vs. 48.3 +/- 16.2; toxic nodular goiter: n = 16; 119.9 +/- 50.7 vs. 48.3 +/- 16.2 nmol/l; P less than 0.001). In contrast, it was decreased in manifest hypothyroidism (n = 25; 24.9 +/- 14.8 vs. 48.3 +/- 16.2; P less than 0.001). In the group of preclinical hyperthyroidism (n = 43), despite suppressed TSH secretion, the serum value of SHBG was normal (47.4 +/- 16.8), while its serum level approached the lower border of the normal range in subclinical hypothyroidism (n = 10; 33.6 +/- 6.1 vs 48.3 +/- 16.2 nmol/l; P less than 0.01). Data indicate that the pituitary responds more sensitively than the liver to a slight change of the serum thyroid hormone level. During thyroid hormone replacement for hypothyroidism, measurement of serum SHBG may provide help to assess the response of the target organ to the given therapy. In patients with generalized resistance to thyroid hormone, the serum SHBG level is within the normal range (51.3 +/- 9.8 nmol/l), thus, its determination supports the diagnosis of this disease.

Biomarkers↗
PubMed1989

[Thyroid function in severe non-thyroidal diseases].

The aim of the present study was to find out whether a change in the function of the pituitary-thyroid axis can be revealed in a relatively homogenous group of hematological patients. To clarify this problem serum levels of total-thyroxine and triidothyronine, free-thyroxine and free-triiodothyronine, reverse-triidothyronine and thyrotropin were detected in these patients. The majority of subjects with chronic myelogenous leukemia (in the remission phase) have normal pituitary-thyroid function, however a change in the peripheral metabolism of thyroxine can be revealed. Longitudinal studies in patients with acute myelogenous leukemia indicate that in some cases with the progression of the disease serum TSH and thyroid hormone levels decrease referring to secondary hypothyroidism and in these cases the measurement of serum free-thyroxine content by an analogue tracer method is not recommended. On the basis of the investigational results it is stated that in hematological patients the pituitary-thyroid function is influenced by the phase of illness and by the results of the given treatment.

Humans↗
PubMed1989

Androgens and bone mineral content in patients with subtotal thyroidectomy for benign nodular disease.

To investigate the influence of thyroid surgery on the skeleton and different hormones a well characterized patient group of 24 women was selected who had undergone subtotal thyroidectomy for euthyroid benign nodular disease and remained euthyroid after the operation. Bone mineral content was determined in lumbar vertebrae, femoral neck and radius by dual and single photon absorptiometry. The serum levels of calcitonin, dehydroepiandrosterone, dehydroepiandrosterone-sulphate, androstenedione, total testosterone, cortisol and 25-hydroxyvitamin D were measured. A control group was created of 48 healthy female subjects. No reduction in bone mass was observed at the measured sites compared to appropriate controls. Beside normal bone mineral content significantly elevated serum levels of dehydroepiandrosterone (27.4 +/- 10.4 vs. 20.8 +/- 6.9 nmol/l) and androstenedione 9.3 +/- 3.3 vs. 6.6 +/- 2.2 nmol/l) were found without any clinical sign of androgen excess. There was no correlation between bone mineral content and these androgen levels. The serum calcitonin levels of all patients were low. With regard to the previously reported interactions among androgen, calcitonin and bone metabolism, our results raise the possibility of a relationship between higher androgen levels and preserved bone mass in these patients, while normal bone mineral content and calcitonin deficiency in these patients does not inevitably indicate that calcitonin does not affect bone tissue in adults.

Adenoma↗