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Cellular response of Shewanella oneidensis to strontium stress.

The physiology and transcriptome dynamics of the metal ion-reducing bacterium Shewanella oneidensis strain MR-1 in response to nonradioactive strontium (Sr) exposure were investigated. Studies indicated that MR-1 was able to grow aerobically in complex medium in the presence of 180 mM SrCl2 but showed severe growth inhibition at levels above that concentration. Temporal gene expression profiles were generated from aerobically grown, mid-exponential-phase MR-1 cells shocked with 180 mM SrCl2 and analyzed for significant differences in mRNA abundance with reference to data for nonstressed MR-1 cells. Genes with annotated functions in siderophore biosynthesis and iron transport were among the most highly induced (>100-fold [P < 0.05]) open reading frames in response to acute Sr stress, and a mutant (SO3032::pKNOCK) defective in siderophore production was found to be hypersensitive to SrCl2 exposure, compared to parental and wild-type strains. Transcripts encoding multidrug and heavy metal efflux pumps, proteins involved in osmotic adaptation, sulfate ABC transporters, and assimilative sulfur metabolism enzymes also were differentially expressed following Sr exposure but at levels that were several orders of magnitude lower than those for iron transport genes. Precipitate formation was observed during aerobic growth of MR-1 in broth cultures amended with 50, 100, or 150 mM SrCl2 but not in cultures of the SO3032::pKNOCK mutant or in the abiotic control. Chemical analysis of this precipitate using laser-induced breakdown spectroscopy and static secondary ion mass spectrometry indicated extracellular solid-phase sequestration of Sr, with at least a portion of the heavy metal associated with carbonate phases.

Bacterial Proteins↗

18 years' experience with high dose rate strontium-90 brachytherapy of small to medium sized posterior uveal melanoma.

AIM: To analyse local tumour control, radiation related complications, visual acuity, enucleation rate, and survival after brachytherapy of small to medium sized choroidal melanoma (CM) with a high dose rate (HDR) strontium-90 (Sr-90) applicator. METHODS: From 1983 until 2000, 98 eyes with CM were treated with Sr-90 brachytherapy. The main outcome measures were actuarial rates of the patients' survival, ocular conservation rate, tumour regression, complication rates, and preservation of visual acuity. End point rates were estimated using Kaplan-Meier analysis. RESULTS: The median follow up time was 6.7 years (0.5-18.8 years). Actuarial melanoma free patient survival rate was 85% (SE 4.8%) after 18 years. Actuarial rate of ocular conservation and complete tumour regression was 90% (SE 3.8%) after 15 years. In 93% local tumour control was achieved, 88% showed a stable scar. Recurrence of the tumour on the border caused enucleation of six eyes (7%). In three cases (4%) retinal detachment was the end point. No cases of optic atrophy or of sight impairing retinopathy outside the treated area were found. Actuarial rate of preservation of visual acuity of 1/10 was 65% at 5 years and 45% at 15 years of follow up (SE 5.9% and 8.8%). CONCLUSIONS: Sr-90 brachytherapy is as effective as iodine or ruthenium brachytherapy for small to medium sized CM but causes fewer complications. The preservation of vision is better than with all other described radioisotopes. HDR Sr-90 brachytherapy can therefore safely be recommended for small to medium sized CM.

Adult↗

Strontium-85 scanning of suspected bone disease.

Strontium-85 scanning of suspected bone lesions in 81 patients has added to the criteria for the diagnosis of malignant and other lesions of bone. Of 46 patients with a previous history of malignant disease and skeletal symptoms negative radiological findings were recorded in 19, but nine of these had positive scans, eight of which when followed up over periods of up to four years proved to be metastatic. A similar prevalence of positive scans occurred in patients without a previous history of malignancy. Because of the anatomical localization of lesions made possible by this technique a tissue diagnosis was made in six patients, while fields of radiotherapy were altered in another seven. This technique can improve the management of patients with suspected bone disease.

Aged↗

Effect of strontium on the contractile properties of postnatally developing rat heart ventricles.

The effects of substitution of calcium (Ca) by an equimolar concentration of strontium (Sr) on isometric contractions of isolated ventricular muscle from postnatally developing rat heart were studied. The duration of contraction and the time-to-peak tension were increased in all age groups although much less in the adult rats than in the neonates. The contractile force was increased in the muscles of rats between 1 and 14 days of age but was depressed in the older animals. The prominent rest-twitch potentiation of neonatal rat heart in Ca-Tyrode was totally eliminated by Sr, whereas a clear rest-twitch potentiation was induced by this cation in the adult rat heart, in which tissue the potentiation is normally absent in Ca-Tyrode. The maximal twitch potentiation by rest in Ca-Tyrode and the positive inotropic effect of Sr substitution grew from birth up to day 9 and from then gradually declined towards the level of adult rat heart by the end of the 3rd postnatal week. The phase of increasing rest-twitch potentiation coincides fairly well with the known development of sarcoplasmic reticulum and the phase of decline with the appearance of the T system of the sarcolemma. It is suggested that the qualitative changes in the contractile properties of developing rat heart during the 3rd postnatal week are due to the more efficient utilization of intracellular calcium stores, owing to the development of the T system.

Animals↗

Strontium-89: treatment results and kinetics in patients with painful metastatic prostate and breast cancer in bone.

Two hundred and two patients with bone pain from metastatic cancer were treated with 40 microCi/kg of Sr-89. Patients were followed with pain diaries, records of medication taken, sleep patterns, serial bone scans and a Karnofsky Index. One hundred and thirty-seven patients with adequate followup survived at least 3 months, including 100 with prostate and 28 with breast carcinoma. Eighty of the 100 patients with prostate cancer responded, and 25 of the 28 breast cancer patients improved. Ten patients with prostate cancer and five with breast cancer became pain free. Little hematologic depression was noted. Sr-89 kinetic studies showed that strontium taken up in osteoblastic areas remained for 100 days. The tumor-to-marrow absorbed dose ratio was 10:1.

Bone Neoplasms↗

Exchange of potassium and strontium in adult bone.

The kinetics of exchange of strontium (85Sr) and potassium (42K) were studied in the mid-tibial cortical bone of 37 adult dogs. After injection of these two tracer cations and tracer-labeled albumin into the tibial nutrient artery, two types of observations were made: 1) collection of sequential venous samples to provide the outflow indicator-dilution curves and to calculate the extraction and retention at early times; and 2) detection of energy-selected gamma emissions via a detector over the tibia to give the time course of content of 42K and 85Sr in the tibia. Extractions of K+ and Sr2+ were 50 and 60% during a single transcapillary passage. More Sr2+ than K+ was retained in the first minutes. Their rates of washout over a 3-h period were similar. The interpretation is that the rate of uptake at extravascular sites is faster for Sr2+ than for K+, as is the rate of release, and that the extravascular volume of distribution for Sr2+ (adsorption sites in the interstitium or on bone) is much larger than that for K+ (intracellular).

Animals↗

Serum hemoglobin levels predict response to strontium-89 and rhenium-186-HEDP radionuclide treatment for painful osseous metastases in prostate cancer.

OBJECTIVE: Retrospective comparative analysis of strontium-89 chloride (Sr89) and rhenium-186-hydroxyethylidene diphosphonate (Re186-HEDP) radionuclide treatment to find predictors of response in patients with painful metastases from hormone refractory prostate cancer. PATIENTS AND METHODS: Clinical data from 60 hormone refractory PCA patients (i.e. rising PSA at castrate testosterone serum levels) was obtained. Twenty-nine were treated with Sr89, 31 were treated with Re186-HEDP for painful osseous metastasis. Response was defined as a patient-reported decrease in pain and/or reduction in pain medication with stable pain level. Hematological parameters and serum levels of PSA, alkaline phosphatase, and lactate dehydrogenase were assessed prior to and at 4-week intervals after treatment. RESULTS: Median survival of all patients was 7 months (95% CI: 6-9 months). Overall, 33/60 (55%) patients reported a decrease in pain after the first radionuclide treatment. This percentage was similar for patients treated with Re168-HEDP and Sr89. Mean duration of reported pain response was 75 days (+/- 68 days) for Sr89 and 61 days (+/- 56 days) for Re186-HEDP, which was not significantly different. A lower blood hemoglobin concentration was associated with a lower pain response rate. In a multivariate Cox regression analysis, pain response to radionuclide treatment predicted longer survival after treatment. CONCLUSIONS: Pain response was present in 55% of patients. Serum hemoglobin concentration prior to radionuclide treatment predicted pain response for both Re186-HEDP and Sr89. A reduction in pain upon radionuclide treatment was associated with a longer survival after treatment.

Aged↗

Myoelectrical and mechanical activity of isolated canine stomach perfused in vitro with fluorocarbon. Role of glucose, phosphate, calcium and strontium in the perfusate.

Myoelectrical and mechanical activities were recorded from whole isolated canine stomachs perfused, intravascularly, with fluorocarbon emulsion, oxygenated in vitro. The perfusate was composed of an oxygen carrier, fluorcarbon, emulsified with a surfactant added to a simulated physiological solution. Bipolar electrodes and a strain gauge were used for recordings. Stomachs perfused as above for 5 h displayed normal electrical and mechanical activities. 'Normal' meaning identical with those observed under in vivo conditions or during perfusion with homologous blood. Normal response to electrical stimulation of a vagus nerve branch or to intraarterial injection of methacholine or pentagastrin were also observed. These functions of smooth muscles were not altered when glucose-free or glucose-and phosphate-free perfusate were used. In calcium-free perfusate, electrical and mechanical activities were absent and no responses to stimulants used were recorded. When calcium was added to the perfusate, these functions were restored to normal. Strontium was found to be an adequate substitute for calcium in fluorocarbon perfusate. Gastric secretions were alkaline and contained fluorocarbon emulsion.

Animals↗

Effects of hyaluronate, strontium and prolonged incubation on different sperm parameters.

The aim of this study was to evaluate the effect of hyaluronate and strontium with short and prolonged incubation periods on different sperm parameters. For sperm intended for in vitro fertilization good progressive motility, a high percentage of normal form, a suitable linear velocity and a low acrosome-reacted proportion of sperm are required. The semen washing procedure in the self-migration method with medium containing hyaluronate Ca2+ after 3 h of incubation complies better with these criteria.

Acrosome↗

[Spontaneous corneal rupture after strontium irradiation of a conjunctival squamous cell carcinoma].

A 87-year-old female patient with a squamous cell carcinoma of the conjunctiva was treated with local strontium-90 irradiation (with a so-called 'Dermaplatte'). In spite of a relatively low dosage, radiotherapy was followed by a corneal ulcer with consecutive rupture of the cornea. The cause of this unexpected perforation was, besides the effect of low-dose irradiation, probably a metabolic disorder of the cornea and a disturbance of the tear film due to the carcinoma which had spread on Bowman's layer of the cornea in an exophytic manner and was accompanied by a dense lymphocytic infiltration. An exenteration was performed and, at the last examination (1 year later), no local recurrence could be detected.

Aged↗

Increased serum cadmium and strontium levels in young smokers: effects on arterial endothelial cell gene transcription.

OBJECTIVE: Metal constituents of tobacco have long been suspected to contribute to cardiovascular diseases. In this study, we determined the serum concentrations of aluminum, cadmium (Cd), cobalt, copper, iron, manganese, nickel, lead, strontium (Sr), and zinc of young nonsmokers, passive smokers, and smokers. METHODS AND RESULTS: Cd and Sr were found to be significantly increased in smokers compared with nonsmokers. The effects of these metals on primary arterial endothelial cells were then assessed using microarray technology and real-time polymerase chain reaction (RT-PCR). The data showed that Sr does not interfere with endothelial cell transcription. In contrast, the effects of Cd in amounts delivered to the human body by smoking were dramatic. CONCLUSIONS: Arterial endothelial cells responded to Cd exposure by massively upregulating metal and oxidant defense genes (metallothioneins) and by downregulating a number of transcription factors. In addition, the mRNA of the intermediate filament protein vimentin, crucial for the maintenance of cellular shape, was reduced. Surprisingly, a number of pro-inflammatory genes were downregulated in response to Cd. The present data suggest that by delivering Cd to the human body, smoking deregulates transcription, exerts stress, and damages the structure of the vascular endothelium; furthermore, in contrast to the effects of cigarette smoke as a whole, Cd seems to possess anti-inflammatory properties.

Adult↗

Mechanism of biphasic contractions in strontium-treated ventricular muscle.

Biphasic contractions were produced in dog trabeculae by replacing 90-95% of the calcium in the bathing solution with strontium. These conditions produced prolonged action potentials accompanied by contractions with two distinct phasic components. The early component disappeared slowly when the remaining Ca++ was removed, whereas the late component was eliminated quickly when Sr++ was removed. Manganese ion (0.25 mM) preferentially decreased the late component without changing the action potential, whereas caffeine and ryanodine decreased or eliminated the early component. Ryanodine did not alter the action potential. Isoproterenol rapidly increased the early component and, more slowly and to a lesser degree, increased the late component. The results suggest that the early component is caused by intracellular release of activator cation, probably from the sarcoplasmic reticulum, whereas the late component is the result of Sr++ entry across the sarcolemma, possibly by way of the slow inward current.

Animals↗

Mechanism of uptake of strontium isotopes in aspergillus lesions.

Observations on experimental aspergillosis of chorioallantoic membranes confirmed that strontium-85 uptake in aspergillus lesions was directly due to infection by the fungus. Such uptake was not found in normal or in Toxoplasma gondii-infected control membranes. Further, the avidity of radionuclide uptake was proportional to the mycelial mass, as previously observed clinically. Investigations on 85Sr containing malt extract broth Aspergillus fumigatus cultures revealed that fungal hyphas did not contain the major proportion of radioactivity, but culture filtrates did, and suggested that a fungal metabolite may be responsible for radiostrontium binding. Subsequent radiochromatography of filtrates obtained from A. fumigatus cultures confirmed the existence of such a metabolite. Several clinical and laboratory observations support the concept that an aspergillus metabolite at foci of infection binds 85Sr and 87mSr.

Aspergillosis↗

Supercritical fluid route for synthesizing crystalline Barium Strontium Titanate nanoparticles.

Pure and well-crystallized Barium Strontium Titanate (BST) nanoparticles with controlled Ba/Sr ratio have been successfully synthesized under supercritical conditions using a continuous-flow reactor in the temperature range of 150-380 degrees C at 26 MPa. To synthesize the Ba0.6Sr0.4TiO3 composition, alkoxides, ethanol and water were used. The resulting nanopowder consists of fine particles with an average particle size of 23 nm. The results show that the Ba/Sr ratio of this powder can be accurately controlled from the composition of precursor. The characterization of the as-synthesized Ba0.6Sr0.4TiO3 solid-solution and the dielectric properties of the sintered ceramics are here reported.

Barium Compounds↗

Palliation of painful bone metastases: Strontium-89.

Most patients with bony metastases experience painful symptoms. Strontium-89 isotope therapy is an alternative to traditional hemibody radiation in cases of multiple, diffuse metastases. Generally given as a single i.v. slow-push infusion, relief begins in one to three weeks, peaks at six weeks, and has a mean duration of 12 months. Up to 22 percent of patients are pain-free at three months.

Bone Neoplasms↗

Grading choroidal neovascular membrane regression after strontium plaque radiotherapy; masked subjective evaluation vs planimetry.

PURPOSE: To analyze angiographic changes in choroidal neovascular membranes (CNVM) after strontium-plaque (90Sr) irradiation for exudative age-related macular degeneration (AMD) using masked measurement of the CNVM areas and a masked subjective comparison of CNVM size and leakage. METHODS: We studied the baseline, 3, 6, and 12-month angiograms of 19 eyes treated with 90Sr-plaque irradiation for exudative AMD. The area of CNVM-related hyperfluorescence was measured quantitatively, and the angiograms were subjectively evaluated by a masked grader. RESULTS: In 7 of the 19 eyes the CNVM-related hyperfluorescence was too scattered to be analyzed by planimetry but masked subjective grading correlated with the clinical response to irradiation. In the remaining 12 eyes, the CNVM decreased in size in 67% of the eyes and showed leakage in 67%. Planimetry and subjective assessment of the size and leakage of the CNVMs similarly reflected the regression after irradiation. CONCLUSIONS: CNVM size and leakage frequently diminish after 90Sr-plaque irradiation. Quantitative measurement of the CNVM areas, or a grading system based on masked subjective assessment, give similar results for evaluating these changes. Masked subjective grading can be used even in cases where the CNVM is too scattered to be outlined for planimetry.

Aged↗

No difference in intestinal strontium absorption after an oral or an intravenous 1,25(OH)2D3 bolus in normal subjects. For the European Study Group on Vitamin D in children with renal failure.

It has been suggested that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) stimulates intestinal calcium absorption less via the intravenous (iv) than the oral route, because the first avoids direct contact of the drug with the enterocytes. However, no study has addressed the issue directly. This investigation was designed to measure the effect of a single oral or iv dose of 1,25(OH)2D3 on calcium absorption, using stable strontium (Sr) as a surrogate for calcium, and measuring the Sr fractional absorbed dose (FAD%) over 240 minutes after Sr administration. In 10 healthy volunteers, five tests were performed in a cross-over design, with a wash-out period between two consecutive tests: Sr absorption without 1,25(OH)2D3 (test A); Sr absorption immediately after either oral (test B) or iv (test C) 1,25(OH)2D3 (1.5 microg/m2 of body surface area [BSA]); Sr absorption (24 hr after either oral (test D) or iv (test E) 1, 25(OH)2D3 (1.5 microg/m2 BSA). The concurrent administration of 1, 25(OH)2D3 and Sr (tests B and C) did not significantly change the area under the Sr FAD%-time curve with respect to test A (test A: 4090 +/- 345; test B: 4510 +/- 345; test C: 4210 +/- 345), whereas Sr absorption was significantly increased (p < 0.001) when Sr was given 24 hr after either oral or iv 1,25(OH)2D3 (test D: 5710 +/- 345; test E: 5510 +/- 345). It was concluded that 1,25(OH)2D3 is likely to influence calcium absorption significantly only via its genomic effect, independent of its administration route.

Administration, Oral↗

Strontium-induced rat egg activation.

Parthenogenetic agents that evoke cytosolic calcium concentration ([Ca2+]i) oscillations similar to those evoked by sperm, mimic fertilization more faithfully than agents that trigger a single [Ca2+]i transient. Strontium chloride (SrCl2) binds to and activates the Ca2+-binding site on the inositol 1,4,5-trisphosphate receptor and evokes [Ca2+]i oscillations. Although SrCl2 has been reported to activate mouse eggs, little is known regarding the pattern of the [Ca2+]i oscillations it evokes in rat eggs and their effect on the early events of egg activation: cortical granule exocytosis (CGE) and completion of meiosis (CM). In the current study we investigated the effect of various concentrations of SrCl2 (2, 4 or 6 mM) on [Ca2+]i, by monitoring [Ca2+]i oscillations in fura-2-loaded rat eggs. Treatment with 2 mM SrCl2 was optimal for inducing the first [Ca2+]i transient, which was similar in duration to that triggered by sperm. However, the frequency and duration of the subsequent [Ca2+]i oscillations were lower and longer in SrCl2-activated than in sperm-activated eggs. The degree of CGE was identical in eggs activated by either sperm or SrCl2, as assessed by semi-quantitative immunohistochemistry combined with confocal microscopy. Evoking 1, 2 or 10 [Ca2+]i oscillations (8, 15 or 60 min in SrCl2 respectively) had no effect on the intensity of fluorescent CGE reporter dyes, while 60-min exposure to SrCl2 caused a delay in CM. Our results demonstrate that SrCl2 is an effective parthenogenetic agent that mimics rat egg activation by sperm, as judged by the generation of [Ca2+]i oscillations, CGE and CM.

Animals↗