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PubMed1987

Center-surround organization of Xenopus horizontal cells and its modification by gamma-aminobutyric acid and strontium.

The properties of axon-bearing horizontal cells were studied by intracellular recording in the light-adapted Xenopus retina. In this adaptational state, the only receptor input was provided by red-sensitive cones. Measurements of response amplitude as a function of stimulus diameter indicated that different units were divisible into two compartments on the basis of their receptive field dimensions: one with a mean length constant, lambda, of 170 microns, the other with lambda = 450 microns. Lucifer Yellow dye injection revealed that units having small receptive fields invariably were cell bodies, whereas units having large receptive fields always were axons. For both horizontal cell bodies and axons, the waveform in response to large spots or annuli consisted of a hyperpolarizing on-transient, followed by a depolarizing rollback to a sustained plateau during light on, and a rapidly depolarizing off-transient that overshot the dark potential level. In contrast, in responses to small spots, the depolarizing rollback was much reduced or absent. However, for small field compartments only, when concentric annular stimuli were flashed around steadily illuminated, small, centered spots, the horizontal cell waveform consisted primarily of a depolarizing potential during light on. This depolarizing component was reduced selectively when the preparation was superfused with Ringer containing 5 mM gamma-aminobutyric acid (GABA). Following a brief exposure to 5-10 mM Sr2+, enhanced oscillatory potentials appeared in the horizontal cell light response during the depolarizing rollback and at light off. The modifications of the depolarizing rollback evoked by Sr2+ were antagonized by GABA. The strontium-induced alterations of the light response were not altered by 6 microM tetrodotoxin (TTX). The results are interpreted in terms of a feedback synaptic action exerted by horizontal cells upon cones, which is expressed as the depolarizing rollback component of the horizontal cell light-evoked waveform. The spatial properties of this component suggest that horizontal cell axons but not horizontal cell perikarya are capable of evoking a feedback signal in the cone. The actions of strontium indicate that calcium currents may play a role in shaping the feedback response. The ability of GABA to antagonize the Sr2+ effect upon the depolarizing rollback indicates that GABA may play a role in feedback.

Animals↗
PubMedDate not supplied

Bioresorption of ceramic strontium-85-labeled calcium phosphate implants in dog femora. A pilot study to quantitate bioresorption of ceramic implants of hydroxyapatite and tricalcium orthophosphate in vivo.

Ceramic hydroxyapatite and tricalcium orthophosphate were radioactively labeled with their strontium-85 analogs. Porous blocks of these materials (dimensions 2.5 X 1.25 X 0.5 cm) were implanted into surgically created defects in dog femora. The fate of the implants was studied by roentgenography, radioactivity measurements, histology, and microradiography. The radioactivity over the implant site was followed for 22 weeks. Implants were retrieved after 20-25 and 50-55 weeks. Hydroxyapatite implants were not affected by biodegradation processes, while tricalcium orthophosphate implants were subject to extensive bioresorption (25%-30% in 22 weeks). Resorption debris from tricalcium orthophosphate implants was found in mononuclear phagocytes and multinuclear osteoclastlike cells. The supposition is that tricalcium orthophosphate is transformed into hydroxyapatite in a physiologic environment. Labeling of ceramic calcium phosphate implants with strontium-85 analogs offers an adequate technique to quantitate bioresorption in vivo.

Animals↗
PubMed1982

Use of strontium as the capture ion in adenyl cyclase histochemical staining of skeletal muscle.

Histochemical staining of adenyl cyclase was performed in muscle specimens. Adenylyl imidodiphosphate (AMP-PNP) was used as the reaction substrate and strontium was used as the capture ion for the liberated phosphate. Staining appeared in the vascular structures between muscle fibers and between muscle fascicles. Substituting lead for strontium as the capture ion resulted in loss of the staining of small vessels between muscle fibers, while indistinct staining of larger vascular structures between muscle fascicles was preserved.

Adenylyl Cyclases↗
PubMed1984

Stereological studies on the epiphyseal growth plate in strontium-induced rickets. With special reference to the distribution of matrix vesicles.

Applying stereological principles, we recently demonstrated a matrix-vesicle distribution between the zones of the epiphyseal growth plate that is at variance with the generally accepted distribution. In the present study of strontium-induced rickets we demonstrated a similar bimodal distribution, the highest matrix-vesicle volume fraction being found in the resting and hypertrophic zones and the lowest, in the proliferative zone. These volume-fraction differences are due to differences in the number of vesicles between zones, the variation in mean diameter being rather small. The disturbed mineralization in strontium-induced rickets is associated with a diminished reduction of the matrix-vesicle volume fraction in the lower part of the growth plate compared with normal animals. The findings may indicate that matrix-vesicle removal is a part of the mineralization process, but a causal connection cannot be proved on the basis of our results. Our findings are, however, compatible with the earlier-posed cell-debris theory for matrix-vesicle origin and distribution.

Animals↗
PubMed1993

Strontium-89 therapy for painful osseous metastatic prostate and breast cancer.

Strontium-89 chloride is a radiopharmaceutical that localizes to actively forming new bone, such as metastatic bone lesions from prostate and breast cancer. It provides effective systemic endo-osseous local radiation therapy to these painful lesions. Strontium-89 will soon be available to physicians in the United States for use in the palliative management of metastatic bone pain.

Bone Neoplasms↗
PubMed1976

[Blastomogenic effect following single and chronic exposure to a mixture of cesium-137 and strontium-90].

The rate of tumor incidence in different rhythms of rat stomach exposure to cesium-137 and strontium-90 was analysed. The correlative values of the administered nucleids activity were selected by analogy with their content in global natural fall-out. In single exposure to the concentrations of 400 and 100 mc/per rat of cesium-137 and strontium-90 mixture accordingly, osteogenic osteosarcomas developed approximatley 4 times as frequently as in chronic administration of the same radionucleids in concentrations of 2 and 8 mc/per rat, correspondingly.

Adenoma↗
PubMed1994

Systemic radionuclide therapy of bone metastases with strontium-89.

Bone metastases can have a devastating effect on a patient's quality of life due to pain and pathologic fractures. Local external beam radiotherapy is very effective for patients with only a few involved areas. Systemic therapy consisting of chemotherapy and hormonal therapy is extremely useful until the patient becomes refractory to treatment. Systemic radionuclide therapy using Strontium-89 has been shown to be very valuable, specifically in patients with bone metastases from hormonally-resistant prostate cancer. Studies have shown a significant improvement in analgesic requirement, time to further radiotherapy, and a reduction in tumor markers with this treatment. The use of Strontium-89 in the treatment of other bone neoplasms and the use of other radionuclides, such as Rhenium-186 HEDP and Samarium-153 EDT-MP, are still investigational.

Bone Neoplasms↗
PubMed1994

One-hour test for estimating intestinal absorption of calcium by using stable strontium as a marker.

Intestinal absorption of calcium is a relevant marker in a broad spectrum of diseases; however, its determination in clinical practice is difficult. Our aim was to design a simple test for this based on stable strontium (88Sr). The correlation between the intestinal absorption of simultaneously administered 45Ca and 88Sr was investigated in patients with various disorders of the bone and calcium metabolism. The area under the curve for the period 0-60 min after dosing (AUC0-60 in mmol.L-1.min), being a representative measure of intestinal absorption, showed a close correlation between both elements (r = 0.90, P < 0.001). Moreover, the measure of agreement in classifying the patients as low, intermediate, or high absorbers was high (kappa = 0.80). We conclude that a test based on measuring AUC0-60 of strontium is a fast and inexpensive way to obtain reliable information about the level of intestinal calcium absorption.

Adolescent↗
PubMed1993

Clinical experience with strontium-89 in prostatic and breast cancer patients.

Bone metastases are a major problem in the clinical management of patients with breast or prostate cancer. Severe bone pain can be a particularly debilitating effect of metastatic disease, resulting in a growing dependency on opioid analgesics and a reduced quality of life in patients who have a short time to survive. The radiopharmaceutical strontium-89 has been demonstrated to be generally well tolerated as well as effective in reducing metastatic bone pain in breast or prostate cancer patients. Unlike other radioisotopes or external radiation treatments, it represents systemic, targeted therapy that is simple and fast to administer in an outpatient setting. Data accumulated over the last 15 years demonstrates that 89Sr provides pain relief in up to 80% of patients with bony metastases arising from breast or prostatic malignancies. Pain palliation is maintained for several months, along with improvements in functional status and quality of life. As many as one fifth of 89Sr-treated patients become pain free and require no further pain medication. The adverse effects of intravenous 89Sr are minimal. Bone marrow toxicity is observed in many patients, resulting in some reduction of platelet and white blood cell counts. Despite reductions of 20% to 30%, these hematologic effects are generally reversible and the majority of patients maintain platelet counts that are within normal limits. Strontium-89 is effective systemic radioisotopic therapy for the palliation of painful bony metastases from breast and prostate carcinoma.

Bone Neoplasms↗
PubMed1996

The treatment of osseous metastases of hormone-refractory prostate cancer with external beam radiotherapy and Strontium-89.

Metastatic bone disease from hormone-refractory prostate cancer can lead to significant morbidity such as pain, nerve compression and fractures which diminishes the quality of life of these patients substantially. Pain from osteoblastic metastases can significantly be improved by both external radiotherapy and Strontium-89 (89Sr), whereas lytic metastases are only responsive to external irradiation. Pain relief is obtained in approximately 80% of patients. Toxicity is mild and retreatment is usually possible. External beam radiotherapy is indicated when spinal cord or nerve root compression is demonstrated, or when osteolytic metastases with danger of fracture are visualized. External radiotherapy and Strontium-89 are important treatments to palliate patients suffering from metastatic prostate cancer. Because of their mild toxicity and highly effective analgesic effect, implementation of irradiation and 89Sr should be start of early in the disease process of these patients in order to keep them ambulatory and pain-free as long as possible.

Bone Neoplasms↗
PubMed1977

[Evaluation of the protective effect of Prussian blue, sodium alginate and calcium phosphate according to tumor development after single and chronic exposure to strontium 90 and cesium 137 mixture].

The mixture of radionuclides was employed in the concentrations of 100.0, 400.0 and 0.8, 2.0 mc/rat for strontium-90 and cesium-137 in single and chronic administration correspondingly. Prussian blue, sodium alginate and calcium were employed in amounts of 50 mg, 800 mg and 258 mg per rat a day. The data obtained are correlated with the results of the same experiments without using the protection. In compared doses of the irradiation the protective action of the substances under study was noted only in chronic experiments. In this case, the appearance of malignant neoplasms was nearly twice less, and the survival was 120 days longer. The absorbed doses were decreased by 17 times for cesium-137 in the whole body and nearly by 4 times for strontium-90 in the skeleton.

Alginates↗
PubMed1997

The role of strontium-89 systemic radiotherapy in the management of osseous metastases from prostate cancer.

Strontium-89 systemic radiotherapy can play a significant role in the palliation of symptomatic osseous metastases from prostate cancer. Given as a single injection, strontium's affinity for osteoblastic activity draws it to all sites of osseous involvement simultaneously. The metastases are bathed with beta-particles whose short range in tissues spares the surrounding normal structures. This article will review the rationale, physiology, and patient selection criteria for its use. Approximately 80% of patients will respond to treatment as documented by the authors experience and by a review of the literature.

Adult↗
PubMed1998

Diagnosis of drowning by combined computer-assisted histomorphometry of lungs with blood strontium determination.

The aim of our study was to examine the combined contribution of computer-assisted histomorphometry of lungs with blood strontium (BS) measurement to the diagnosis of drowning in cadavers recovered from fresh water. The study population comprised 116 drowned subjects. The results for this group were compared with those obtained for three non-drowned groups: 22 subjects who died from causes other than asphyxia, 13 subjects who died of asphyxia (strangulation or hanging); and 23 healthy living subjects in whom normal BS level was measured. Samples of water where the bodies had been found were analyzed in order to establish a relation with the BS concentration of the drowned subjects. Histologically, each type of pulmonary lesion (congestion, edema, alveolar macrophages, alveolar hemorrhage, and emphysema aquosum) was evaluated semiquantitatively using a score according to the severity of the pathology. Then, a quantitative histomorphometric study was performed using a computer-assisted image analyzer to measure the length and thickness of the alveolar walls, and the area and density of the alveolar cavities. The mean values of the BS levels in the 116 drowned subjects and of the water strontium concentrations were found to be much higher than in the living individuals. Although the ranges were wide, we found no overlap between values found in drowned subjects and those in non-drowned subjects. Emphysema aquosum and to a lesser extent alveolar hemorrhage were found to be the most significant histologic changes in the drowned and asphyxia groups compared with the nonasphyxia control groups.

Drowning↗
PubMed2001

Synthesis of Strontium Ferrite Ultrafine Particles Using Microemulsion Processing.

The strontium ferrite ultrafine particles have been prepared using the microemulsion processing. The mixed hydroxide precursor was obtained via the coprecipitation of Sr(2+) and Fe(3+) in a water-in-oil microemulsion of water/CTAB/n-butanol/isooctane. According to the investigation on the thermochemical properties by TGA/DTA and the phase analysis by XRD, it was shown that the precursor could yield pure strontium ferrite after calcination at 700 degrees C for 5 h while using an appropriate molar ratio of Sr/Fe in microemulsions. From TEM measurement, the diameters of the precursor and calcined particles were 3.8+/-0.7 and 50-100 nm, respectively. The magnetic properties characterized by a SQUID magnetometer showed that the saturation magnetization, remanent magnetization, coercivity, and squareness ratio were 55 emu/g, 28 emu/g, 492 Oe, and 0.51, respectively. The magnetization was also observed to increase with the decrease of temperature at 5-400 K. Compared with those reported earlier, the quite low coercivity implies the potential application of final product in the high-density perpendicular recording media. Copyright 2001 Academic Press.

Journal Article↗
PubMed2002

Strontium adsorption properties of an aluminum-pillared montmorillonite carrying carboxylate functional groups.

Strontium adsorption was studied in an aluminum-pillared montmorillonite (PILC) carrying organic acid groups. The in situ dissociation of these groups increases the number of negative sites in the modified PILC, promoting thus the uptake of cations from an exchange solution. To investigate the role of solution pH and acid strength in cation uptake phenomena, base titrations were performed for PILCs carrying either oxalate or acetate groups. Comparison with the pristine PILC showed that extra Sr(2+) uptake initiated at pH 6 and 8 in the presence of oxalate and acetate, respectively. The overall increase in Sr(2+) uptake was higher in the presence of oxalate and amounted to about 136% as compared with the pristine PILC, at pH slightly above 8. The effect of the acid's strength was further probed through strontium adsorption isotherms, taken at a constant pH for PILC samples carrying acetate, oxalate, malonate, or citrate groups. The results demonstrate that cation uptake can be optimized by tuning the pH conditions to the acid's strength or vice versa.

Journal Article↗
PubMed2003

Is the calcium receptor a molecular target for the actions of strontium on bone?

The extracellular calcium-sensing receptor (CaR) plays key roles in maintaining extracellular calcium homeostasis by enabling several of the cells and tissues involved in this process to sense small changes in Ca(2+)(o) and to respond with changes in cellular function that will restore Ca(2+)(o) to its normal level. The chief cells of the parathyroid gland and the thyroidal C-cells, for example, respond to decreases in Ca(2+)(o) with increased secretion of the Ca(2+)(o)-elevating hormone, parathyroid hormone (PTH), and decreased secretion of the Ca(2+)(o)-lowering hormone, calcitonin, respectively. The cells of the renal distal tubule are likewise capable of sensing Ca(2+)(o) and respond to decreases in Ca(2+)(o) with increased tubular reabsorption of Ca(2+) and vice versa, alterations in tubular function that will contribute to normalization of Ca(2+)(o). The skeleton also plays key roles in maintaining Ca(2+)(o) homeostasis and both osteoblasts and osteoclasts can sense Ca(2+)(o), with elevations in Ca(2+)(o) promoting bone formation and inhibiting bone resorption. It has been suggested that Sr(2+) could act on bone via the CaR; however, the molecular mechanisms through which Ca(2+)(o) and Sr(2+)(o) exert these actions on bone cells remain controversial. Therefore, identifying their molecular target(s) would have significant implications for the treatment of bone loss. Ideally, therapies should simultaneously inhibit bone resorption while stimulating bone formation. Administration of strontium produces exactly those effects. Previous studies with dispersed bovine parathyroid cells as well as a preliminary study using CaR-transfected Chinese hamster ovary (CHO) cells indicate that Sr(2+)(o) is an agonist of the CaR, albeit with slightly lower efficacies and potencies than Ca(2+)(o). Given that Sr(2+)(o) is distributed preferentially in bone, therefore, an action of this divalent cation on the CaR in bone cells represents one possible mechanism by which strontium ranelate, a new antiosteoporotic drug, exerts it skeletal actions in vivo.

Animals↗
PubMed2002

Prevention of early postmenopausal bone loss by strontium ranelate: the randomized, two-year, double-masked, dose-ranging, placebo-controlled PREVOS trial.

Early postmenopausal women ( n = 160) were randomised to receive placebo or strontium ranelate (SR) 125 mg/day, 500 mg/day or 1 g/day for 2 years (40 participants per group). All participants received calcium 500 mg/day. The primary efficacy parameter was the percent variation in lumbar bone mineral density (BMD), measured using dual-energy X-ray absorptiometry. Secondary efficacy criteria included hip BMD and biochemical markers of bone turnover. At month 24, SR 1 g/day significantly increased lumbar BMD compared with placebo [mean (SD) +5.53% (5.12); p<0.001] for measured values and [mean (SD) +1.41% (5.33%); p<0.05] for values adjusted for bone strontium content. The annual increase for adjusted values was +0.66% compared with -0.5% with placebo, with an overall beneficial effect after 2 years of about 2.4% with SR 1 g/day relative to placebo. There were no other significant between-group differences in adjusted lumbar BMD. Femoral neck and total hip BMD were also significantly increased at month 24 with SR 1 g/day compared with placebo [mean (SD): +2.46% (4.78) and +3.21% (4.68), respectively; both p<0.001)]. SR 1 g/day significantly increased bone alkaline phosphatase at all time points ( p<0.05) compared with baseline and between-group analysis showed a significant increase, compared with placebo, at month 18 ( p = 0.048). No effect on markers of bone resorption was observed. SR was as well tolerated as placebo. The minimum does at which SR is effective in preventing bone loss in early postmenopausal non-osteoporotic women is therefore 1 g/day.

Analysis of Variance↗
PubMed1996

The divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro.

In this study, we have determined the effect of the divalent strontium salt S12911 on bone cell replication and bone formation in two culture systems. In the first series of experiments, half-calvariae of newborn rats were cultured with S12911 from 24 to 96 h and labeled with 3H-thymidine for the last 6 h of culture or treated with S12911 for 24 h and labeled for 24 h with 3H-proline 24-48 h after the removal of the agent. Calvariae were then processed for histomorphometry. S12911 at 10(-3) M increased the replication of preosteoblastic cells by 30-50% after 24 h and by 60% after 96 h of treatment. This effect was specific, since the number of labeled osteoblasts and of periosteal cells was not changed. A transient 24 h treatment with S12911 at 10(-3) M increased bone formation 24 and 48 h after the removal of the agent. 3H-proline labeled surfaces and bone formation rates were increased by 20%-35%. In the second series of experiments, sequential collagenase digestions were used to isolate cell populations enriched in fibroblasts or osteoblasts (Ob) from 22 day fetal rat calvariae. Treatment with S12911 at 10(-3) M for 24 h enhanced DNA synthesis by three- to fourfold in cell populations enriched in fibroblasts and preosteoblastic cells. The effect was less pronounced and inconsistent in Ob cells. S12911 at 10(-3) M for 24 h also increased collagen and non-collagen protein synthesis by 35% in Ob cells. These data indicate that the divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro, an effect that may contribute to the previously reported effects of S12911 on trabecular bone mass in vivo.

Animals↗