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During a ten-year period, 211 patients with a diagnosis of pterygium were treated in the University of Texas Medical Branch by a combined effort using a strontium 90 beta ray applicator immediately after surgical excision. Only one patient developed recurrence. No complications were observed during the first year of follow-up.
Systemic radionuclide therapy with strontium chloride Sr 89 is a rediscovered alternative to relieve pain from bony metastases. Although numerous advances have been made in the diagnosis and treatment of cancer, pain remains a serious and debilitating disease complication. An increasing number of clinical trials are reporting satisfactory results with 89Sr-chloride therapy, now available for widespread clinical use. We have treated 11 patients with this radionuclide; of these patients, 8 had excellent to dramatic pain relief and 3 had mild to moderate improvement. Clinical response was based on subjective pain relief, increased mobility, decreased analgesic uptake, and/or improvement in daily activities, including work habits.
PURPOSE: Strontium-89 (Sr-89) chloride is an effective palliative treatment of the bone metastases of prostate cancer. Chemotherapy has also been shown to have a palliative benefit in this disease. We aimed to determine the benefits and complications of Sr-89 therapy in patients with prostate cancer who had become refractory to chemotherapy. We conducted a retrospective review of 14 treatments administered to 13 patients with chemotherapy-resistant and hormone-resistant prostate cancer. RESULTS: Of the 14 administered treatments, 8 (57%) resulted in improved pain control, with 2 patients able to stop analgesia. The median duration of response was 56 days. No prostate-specific antigen response was seen in the 8 patients tested. There was significant and prolonged bone marrow toxicity, with 6 patients requiring red blood cell transfusion. Prolonged thrombocytopenia was seen, with platelet counts remaining below baseline levels after treatment in all but one patient. Leukopenia was generally mild and not associated with infection. CONCLUSIONS: Sr-89 is an effective treatment of patients with chemotherapy-refractory prostate cancer, but careful and prolonged monitoring of hematologic parameters after therapy is required.
Calcium plays a pivotal role in the pathogenesis of amoebiasis, a major disease caused by Entamoeba histolytica. Two domains with four canonical EF-hand-containing calcium-binding proteins (CaBPs) have been identified from E. histolytica. Even though they have very high sequence similarity, these bind to different target proteins in a Ca2+-dependent manner, leading to different functional pathways. Calcium-binding protein-2 (EhCaBP2) crystals were grown using MPD as a precipitant. The crystals belong to space group P2(1), with unit-cell parameters a = 111.74, b = 68.83, c = 113.25 A, beta = 116.7 degrees. EhCaBP2 also crystallized in complex with strontium (replacing calcium) at similar conditions. The crystals belong to space group P2(1), with unit-cell parameters a = 69.18, b = 112.03, c = 93.42 A, beta = 92.8 degrees. Preliminary data for EhCaBP2 crystals in complex with an IQ motif are also reported. This complex was crystallized with MPD and ethanol as precipitating agents. These crystals belong to space group P2(1), with unit-cell parameters a = 60.5, b = 69.86, c = 86.5 A, beta = 97.9 degrees.
Strontium (Sr2+) can substitute for Ca2+ and stimulate a variety of functions of numerous types of cells. The purpose of this study was to investigate the details of the biologic effects of Sr2+ on human keratinocyte growth, cell cycle, viability, and differentiation and to compare these effects with Sr2+ effects on cultured skin melanocytes. Cultured keratinocytes stimulated with 1.0-3.0 mM Sr2+ showed higher viability and almost a twofold increase in cell number compared with those grown in a standard calcium concentration. Time course studies revealed that 2.0 mM Sr2+ had no effects on growth of cultured melanocytes or fibroblasts. Sr2+ increased the percentage of cultured keratinocytes in G2/M phase, with a decrease in cells in G0/G1 phase. This effect of Sr2+ on the cell cycle was not seen in cultured melanocytes or fibroblasts. A 2 mM concentration of Sr2+ produced an increase in low-density keratinocytes separated by a Percoll gradient. In addition, increased expression of human fibronectin was observed in the cytoplasm and on cell membranes of keratinocytes cultured in Sr2+. Sr2+ can be of practical benefit in the culture of human keratinocytes in serum-free medium, increasing the viability and proliferative rate and producing a more uniform population of basaloid cells with increased expression of cell surface fibronectin.
1. The effects of strontium ions, Sr2+, on Ca(2+)-dependent feedback mechanisms during excitation-contraction coupling were examined in voltage-clamped rat ventricular myocytes in which intracellular [Ca2+] and [Sr2+] were monitored with the fluorescent indicator, indo-1. 2. Voltage clamp depolarizations and caffeine applications during superfusion in Ca(2+)-free, Sr(2+)-containing solutions were employed to exchange intracellular Ca2+ with Sr2+. Myocytes were loaded with Sr2+ by applying voltage clamp depolarizations during superfusion in Na(+)-free, Sr(2+)-containing solutions. 3. Caffeine applications produced large fluorescence transients in Sr(2+)-loaded cells. Thus, Sr2+ could be sequestered and released from the sarcoplasmic reticulum. 4. Ca2+ influx, but not Sr2+ influx, via sarcolemmal Ca2+ channels evoked ryanodine-sensitive fluorescence transients in Sr(2+)-loaded cells. These results demonstrated that Ca2+ influx-induced Sr2+ release (CISR) from the sarcoplasmic reticulum occurred in these experiments, even though Sr2+ influx-induced Sr2+ release was not observed. 5. The amplitude of the Ca2+ influx-induced fluorescence transient was 17 +/- 1% of the caffeine-induced transient (n = 5 cells), an indication that fractional utilization of Sr2+ sequestered in the sarcoplasmic reticulum during CISR was low. 6. With increased Sr2+ loading, the amplitude of Ca2+ influx- and caffeine-induced fluorescence transients increased, but fractional utilization of sarcoplasmic reticulum divalent cation stores was independent of the degree of Sr2+ loading. These data suggest that Ca2+ influx directly activated the release of divalent cations from the sarcoplasmic reticulum, but mechanisms promoting positive feedback of Sr2+ release were minimal during CISR. 7. By comparison, in Ca(2+)-loaded myocytes, Ca2+ influx-induced Ca2+ release (CICR) utilized a greater fraction of caffeine-releasable stores than CISR. Fractional utilization of Ca2+ stores during CICR increased with the degree of Ca2+ loading. 8. Taken together, these results suggest that Ca(2+)-dependent feedback mechanisms play a major role in determining the extent of sarcoplasmic reticulum Ca2+ release during cardiac excitation-contraction coupling under a wide range of conditions.
Calcium ion alone or in the presence of added calmodulin stimulated in vitro transfer of 32P from [gamma 32P]ATP into several proteins of mitochondrial and synaptosomal particulate fractions from rat brain. Strontium ion was capable of substituting for calcium ion in this stimulation, but barium ion lacked this capacity. These results bring into question the hypothesis that calcium-dependent protein phosphorylation of synaptic proteins is intrinsic to neurotransmitter release during neurotransmission, but they do not rule out that possibility.
2 strontium chloride hexahydrate-containing dentifrices (SCH), similar except for their respective abrasive systems, diatomaceous earth or silica-based, were compared for their effects on plaque accumulation and gingival inflammation as part of a 2-month randomised double-blind parallel clinical study. No attempt was made to change the patients' oral hygiene prior to participation in the study. Plaque was assessed using the Silness & Löe index and the gingival condition by the Löe & Silness index GI. There was a slight and non-significant increase in plaque accumulation at 2 weeks from baseline, but relatively negligible change thereafter, the effect being identical in both groups. Similarly, the gingival condition showed a slight index change from baseline, although it tended to be slightly higher in the diatomaceous earth group. The results do not support the conclusions of previous studies which indicated that SCH dentifrices increased plaque accumulation. Neither plaque accumulation nor gingival condition significantly changed from baseline levels during the course of the study.
As part of an epidemiologic study conducted in seven towns in Wisconsin, U.S.A., enamel mottling, opacities, and pigmentations were assessed in 1, 313 12- to 14-year-old schoolchildren. Enamel mottling was found to increase in prevalence and severity as strontium concentrations in communal drinking water increased. This trend held for lifelong residents only, and could not be demonstrated among children who immigrated to the towns after 1 year of life. No relationship of enamel mottling and water fluoride concentrations was found.
Thirty schoolchildren, 9-12 yr old with high DMF score, rinsed their mouths twice a day for 3 days with a chlorhexidine-fluoride (CXF) solution or a chlorhexidine-fluoride-strontium (CXFSr) solution. Streptococcus mutans counts (CFU) were made from saliva incubated on MSB agar and the gingival bleeding was recorded both before and after the rinsing period. S. mutans count decreased significantly immediately after the rinsing with each of the solutions (from 650 X 10(3) to 170 X 10(3) CFU/ml by CXF and from 500 to 170 X 10(3) CFU/ml by CXFSr). Within about 18 days after the rinsing with each solution the salivary S. mutans counts returned to the original level. Gingival Bleeding Index (GBI) was significantly reduced by half through the CXF rinsing while the slight reduction by CXFSr was nonsignificant. Both of these changes were temporary. The results suggest that short rinsing periods with the CXF solution may be more advisable than daily rinses as a contribution to the maintenance of oral health in subjects or groups in need of such a prophylaxis. The weaker effect found with the CXFSr solution suggests that the cariostatic effect recently found in rats with the same solution may be due to other mechanisms than reduction of the oral S. mutans count.
In order to find out if it is possible to prevent caries and gingivitis by periodical use of chlorhexidine-fluoride mouthrinses with or without strontium, and to find out what effects they have on salivary mutans streptococci and lactobacilli counts, a total of 243 schoolchildren aged 11 yr with high DMFS scores were randomly divided into four groups. One group (C) served as a basic control. Subjects in the second group (CXF) rinsed their mouths twice a day every third week with a rinsing solution containing 0.05% chlorhexidine gluconate and 0.04% NaF. In the third group (CXFS) the rinsing solution contained 500 ppm Sr during the first and second year and 15 ppm during the last 6 months, in addition to chlorhexidine and fluoride. In the fourth group (CX) the solution contained only 0.05% chlorhexidine gluconate. All the rinsing solutions had pH 5.8 buffered with succinic acid-NaOH buffer. After 2 yr and 9 months, the mean DMFS (SD) increments in the C, CXF, CXFS, and CX groups were 3.8 (5.7), 2.5 (3.2), 3.5 (4.8), and 3.4 (5.5), respectively. The percentage of subjects with bleeding gingival units had decreased from initial to final values as follows: C, 81-38; CXF, 88-42; CXFS, 89-56; CX, 89-37. The number of lactobacilli and mutans streptococci in saliva remained virtually unchanged throughout the study. For caries increment and gingival bleeding, the differences between groups were not statistically significant. The chlorhexidine-fluoride combination tended to prevent caries, but the effect on gingival bleeding and salivary counts of mutans streptococci and lactobacilli was negligible.
The effect of Strontium (Sr) and Manganese (Mn) was studied on freshly isolated chondrocytes obtained from costal cartilage of young male rats. Cells isolated from rats rendered rachitic by oral exposure to Sr or Mn exhibited a decreased synthesis of glycosaminoglycans and collagen as judged by incorporation of 35SO4 and 3H proline. In vitro exposure of chondrocytes from untreated (control) animals to Sr or Mn at concentrations comparable to those found in cartilage from Sr and Mn rachitic rats, lowered the O2 consumption in both groups, but only Sr had any influence on the other parameters studied.
Potassium-induced contractions were studied in muscle fibres from Megabalanus psittacus (Darwin) in an attempt to establish the requirement of extracellular calcium for the development of force. A sudden elevation of external potassium induced the production of contractures and/or twitches only if calcium was present. In calcium-free solutions no contraction or action potential occurred. When external calcium was replaced by barium, potassium-induced depolarizations accompanied by several action potentials did not generate either contractures or twitches. With strontium in place of calcium, action potentials of different duration were observed. Only the long-lasting ones (a few seconds) induced twitches.
1. The interaction between Ca and Sr ions on quantal transmitter release at the frog neuromuscular junction was studied, using conventional electrophysiological techniques.2. While Ca ions always activate transmitter release, the activating action of Sr ions depends on the Ca ion concentration in the medium; at low [Ca], strontium ions enhance the release, but at higher [Ca] they inhibit it. It is postulated that there is a [Ca] at which Sr ions do not affect transmitter liberation.3. When Sr activates release, its effect and the effect of Ca add in a more than linear fashion.4. Magnesium ions inhibit the release induced by Sr.5. The results can be explained by assuming that Ca and Sr act on the same site, at some stage of the process of quantal transmitter release. The affinity of both ions towards the sites is approximately the same, but the effectiveness of Sr is much smaller.
1. Histamine release from peritoneal mast cells of the rat was stimulated when the cells were exposed for 10 min to sodium-deficient media where all NaCl had been replaced by KC1, RbC1, glucose, sucrose, mannitol, or Tris, provided calcium was less than about 0-5 mM. 2. Light and electron microscopy showed the response to be exocytosis. 3. The chelating agents, EDTA and EGTA, abolished the response to sodium lack and their inhibitory effects were reversed by re-incubating cells with calcium but not magnesium. 4. The response was inhibited by dinitrophenol combined with glucose-deprivation. 5. The response was inversely related to the concentrations of sodium and calcium below 137-5 and 0-5 mM respectively. 6. The related alkaline earth metals, barium, strontium, and magnesium, resembled calcium in inhibiting the response to sodium lack. 7. No secretory response was seen when the cells were exposed for 10 min to calcium-free medium in which lithium replaced sodium. Exposure to this medium for 60 min, however, elicited secretion. 8. It is concluded that when extracellular calcium is low, a reduction in extracellular sodium induces a conventional exocytotic secretory response dependent on energy and cellular calcium. It is suggested that sodium lack may mobilize calcium from a cellular site possibly the inner aspect of the plasma membrane.
1. The strontium content of squid axons averages 2.9 mumol kg-1 axoplasm and squid blood contains 75 mumol Sr l-1. The bulk of the Sr inside axons is bound, possibly within mitochondria. Sr seems to be handled by squid axons in an essentially similar manner to Ca. 2. Sr uptake is increased by electrical activity, by lowering external Na, by depolarization with K and by poisoning with cyanide or FCCP. Uptake is unaffected by ouabain. 3. Sr efflux has a Q10 of 2.2. Efflux can be divided operationally into three components: one dependent on external Ca (or Sr), one dependent on external Na and a residual component that can be inhibited by external lanthanum or internal vanadate. 4. Poisoning an axon with cyanide or FCCP results in a large increase in Sr efflux which can be divided operationally into two components: one dependent on external Ca (or Sr) and one dependent on external Na.
1. Strontium can replace calcium in a number of physiological and biochemical processes. The effects of Sr2+ were investigated in enzymatically isolated ventricular myocytes of the guinea-pig. Action potentials and membrane currents were measured with the patch-clamp technique used in the whole-cell recording configuration. Mechanical activity was assessed utilizing a laser-light diffraction system for sarcomere length measurements in single heart cells. 2. When experiments where carried out using 2 mM-Sr2+ to replace 2 mM-Ca2+ action potentials were found to be prolonged up to severalfold. Voltage-clamp experiments revealed that the slow inward current (Isi) inactivated more slowly. With Ca2+ replaced by Sr2+, the onset of the twitch was delayed, the maximum shortening was increased and a marked voltage-dependent tonic shortening developed. 3. Voltage-clamp pulses of 3.3 s duration were applied to investigate changes of the steady-state current-voltage relationship produced by replacing Ca2+ with Sr2+. Large slow changes of membrane currents produced by Sr2+ were observed. The identity and time course of these currents were investigated after blocking Isi and potassium currents pharmacologically. The remaining current had many of the characteristics of 'creep currents' (Eisner & Lederer, 1979; Hume & Uehara, 1986 a, b). The creep currents were found to be paralleled by changes of the intracellular Sr2+ concentration, as determined by tracking the sarcomere length during the accompanying tonic contractions. 4. The creep currents were suppressed by Ni2+ (2 mM), a finding that suggests that the Na+-Ca2+ exchanger may be responsible for producing these currents (Kimura, Miyamae & Noma, 1987). The question remains, however, whether the Na+-Ca2+ exchanger is responsible for generating the currents itself or whether it may influence another current source by changing the intracellular Sr2+ concentration. 5. To test the role of the Na+-Ca2+ exchanger in producing the creep currents, the reversal potential of the creep current was investigated. Simple voltage protocols were inadequate to distinguish between the two current sources. However, loading the cytosol with Sr2+ by means of a second pipette sealed to the same cell in the presence of Ni2+ as an inhibitor of the Na+-Ca2+ exchanger revealed difference currents compatible with a non-specific cationic channel activated by intracellular Sr2+ (Ehara, Noma & Ono, 1988). 6. In conclusion, the creep currents produced when Ca2+ is replaced by Sr2+ appear to arise from an increase of intracellular Sr2+ which activates a non-specific cation channel. A contribution from the Na+-Ca2+ exchanger can not be excluded.
The influence of modified plasma membrane fatty acid composition on cellular strontium accumulation in Saccharomyces cerevisiae was investigated. Growth of S. cerevisiae in the presence of 1 mM linoleate (18:2) (which results in 18:2 incorporation to approximately 70% of total cellular and plasma membrane fatty acids, with no effect on growth rate) yielded cells that accumulated Sr2+ intracellularly at approximately twice the rate of S. cerevisiae grown without a fatty acid supplement. This effect was evident over a wide range of external Sr2+ concentrations (25 microM to 5 mM) and increased with the extent of cellular 18:2 incorporation. Stimulation of Sr2+ accumulation was not evident following enrichment of S. cerevisiae with either palmitoleate (16:1), linolenate (18:3) (n-3 and n-6 isomers), or eicosadienoate (20:2) (n-6 and n-9 isomers). Competition experiments revealed that Ca2+- and Mg2+-induced inhibition of Sr2+ accumulation did not differ between unsupplemented and 18:2-supplemented cells. Treatment with trifluoperazine (TFP) (which can act as a calmodulin antagonist and Ca2+-ATPase inhibitor), at a low concentration that precluded nonspecific K+ efflux, increased intracellular Sr2+ accumulation by approximately 3.6- and 1.4-fold in unsupplemented and 18:2-supplemented cells, respectively. Thus, TFP abolished the enhanced Sr2+ accumulation ability of 18:2-supplemented cells. Moreover, the rate of Sr2+ release from Sr2+-loaded fatty acid-unsupplemented cells was found to be at least twice as great as that from Sr2+-loaded 18:2-enriched cells. The influence of enrichment with other fatty acids on Sr2+ efflux was variable. The results reveal an enhanced Sr2+ accumulation ability of S. cerevisiae following 18:2-enrichment, which is attributed to diminished Sr2+ efflux activity in these cells.