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A 10-day course of ultraviolet radiation (intensity: 1/8-2 biodoses daily) did not favour accumulation of cesium-137 in the body but produced some effect on the accumulation of strontium-90. In the real radiation condition in the city of Kiev the daily prophylactic 1/8 biodose may be considered as absolutely safe.
In order to elucidate the role of Kupffer cells in granuloma formation in the liver of mice under a condition of severe monocytopenia induced by administration of strontium-89, granulomas were produced by particulate glucan injection and examined histopathologically, immunohistochemically, by [3H]thymidine autoradiography, and in culture experiments. Hepatic granulomas were smaller, less numerous, and more irregularly shaped in the monocytopenic mice than in the control mice. The granulomas were composed of multinuclear giant cells, epithelioid cells, Kupffer cells, and T lymphocytes, but not monocytes or granulocytes. Kupffer cells were heavily labeled with [3H]thymidine in the monocytopenic mice, particularly just before the stage of granuloma formation, and then clustered in the liver sinusoids. At 8 days, they formed granulomas, transformed into epithelioid cells, and transformed further into multinuclear giant cells. Although the culture of liver cell suspensions prepared from the livers of monocytopenic mice sustained diffuse proliferation of macrophages on a monolayer of mouse stromal cell line (ST2), no monocyte/macrophage colonies were formed. From these results, it is reasonable to conclude that Kupffer cells alone are activated in a condition without a supply of monocytes from peripheral blood; proliferate and cluster in the hepatic sinusoids; transform into peroxidase-negative macrophages, epithelioid cells, and multinuclear giant cells; and participate in granuloma formation in loco together with T lymphocytes.
At the University of Kansas Medical Center, systemic use of strontium 89 ((89)Sr), a betaemitting radioisotope, was evaluated in the treatment of metastatic carcinoma to bone for relief of bone pain. Eighty-five patients were treated with systemic (89)Sr in the dosage of 30 to 40 μCi/kg. All patients had multiple bone metastases, the majority with primary breast or prostatic cancer. The response to treatment was evaluated by daily diary entries, changes in the amount of pain medication, periodic bone scans, and other laboratory values.In the patients who survived (47) and who were observed for three or more months, overall results showed 15 percent becoming pain free; 23 percent showed marked improvement with decreased consumption of pain medication; 53 percent showed mild but significant improvement in pain relief and decrease in pain medication requirement; and 9 percent showed no improvement. No patients noted a worsening of bone pain after the treatment. There was a combined favorable response in 91 percent (43/47) of patients with some meaningful palliation after (89)Sr therapy. This study, using (89)Sr systemic therapy, suggests that this isotope may be a valuable adjuvant therapy for palliation of pain from metastatic bone lesions.
Normal human bronchial epithelial cells were infected with SV40 virus or an adenovirus 12-SV40 hybrid virus, or transfected via strontium phosphate coprecipitation with plasmids containing the SV40 early region genes. Colonies of morphologically altered cells were isolated and cultured; these cells had extended culture lifespans compared to normal human bronchial epithelial cells. All cultures eventually underwent senescence, with the exception of one which appears to have unlimited proliferative potential. Colonies arising after viral infection were screened for virus production by cocultivation with Vero cells; only viral nonproducer cultures were analyzed further. The cells retained electron microscopic features of epithelial cells, and keratin and SV40 T-antigen were detected by indirect immunofluorescence. All of the cultures were aneuploid with karyotypic abnormalities characteristic of SV40-transformed cells. No tumors formed after s.c. injection of the cells in nude mice. These cells should be useful for studies of multistage bronchial epithelial carcinogenesis.
Neonatal human prostatic epithelial cells (NP-2s) were transfected by strontium phosphate coprecipitation with a plasmid (pRSV-T) containing the SV40 early region genes. The cells transfected with pRSV-T, but not the sham-transfected controls, formed rapidly growing, multilayered colonies within 2 weeks at a frequency of 1 x 10(-4) in a serum-free medium (P4-8F). In all, 28 colonies of transformed cells were isolated. Three of these have been cultured for a sufficient length of time to show that their growth potentials are well beyond that of the normal progenitor cells (NP-2s). There is also little or no indication of the culture "crisis" commonly seen in SV40-transformed cells in these transfected lines. All contain cytokeratins and SV40 T-antigen as revealed by immunofluorescence, have ultrastructural features of epithelial cells, and are pseudodiploid. None have produced tumors within 1 year after s.c. injection into nude mice. The transformed as well as the parental NP-2s cells require bovine pituitary extract for growth in serum-free medium and are stimulated by transforming growth factor beta 1 (TGF-beta 1) and epidermal growth factor in clonal growth assays. In contrast, a prostatic carcinoma cell line (PC-3) is inhibited by TGF-beta 1. This serum-free system and immortalized transfected clones will be useful for studying the action of putative prostatic carcinogens and tumor-promoting agents.
High-performance liquid chromatography using spherical aggregates of strontium-phosphate hydroxyapatite(SrHA) micro-crystals as adsorbent has been developed; preliminary performance tests were carried out by using several types of protein. It can be deduced that, in parallel with the case of usual calcium-phosphate hydroxyapatite(CaHA), with SrHA also, two types of effective surface, vector a (or vector b) and vector c surfaces, appear on the crystal: the same protein molecular generally shows slightly different chromatographic behaviors between the CaHA and the SrHA packed column. Combining the SrHA and the CaHA packed column would lead to an efficient fractionation of a particular molecule from an assembly of molecules with subtle structural differences from one another.
In experiments on Wistar rats it was shown that homologous immunoglobulin (a single dose of 25 mg/kg), with normal antitissue antibodies, subcutaneously injected in the following manner: a single injection 90 days or 6 months, or double injection 3 and 6 months after intraperitoneal administration of strontium 90 (11.1 kBq/kg) reduces osteosarcoma occurrence and increases the average lifetime of animals.
The 234 foods from a 1984 collection of the Food and Drug Administration's Total Diet Study were analyzed for the trace elements molybdenum, nickel, cobalt, vanadium, and strontium by plasma emission spectrometry. Daily intakes of these elements were then estimated for eight age-sex groups on the basis of results from national food consumption surveys. The contribution of food commodity groups to the daily intake of the five elements and the distribution of the elements in the 234 foods were also determined. Results from this study were compared with those reported earlier from other laboratories.
The purpose of this study was to evaluate the potential of pulmonary alveolar macrophage (PAM) and interstitial cell division as local sources of PAM in the absence of migratory monocytes. Male B6C3F1 mice were treated with Strontium-89 to deplete the levels of circulating monocytes. Normal and irradiated mice were then instilled intratracheally with carbon particles to increase the demand for PAM. Dividing cells were labeled with tritiated thymidine. The proportion of tritiated thymidine-labeled cells was then determined in lavaged PAM and in IC of lung tissue as an indicator of the proliferative response associated with the demand for increased number of PAM. It was hypothesized that, in the absence of circulating monocytes as a source of PAM, cell division of the local source of PAM would be greater in the monocyte-depleted mice than in the normal mice. It was found that proliferation of lavaged PAM was 112% greater in the monocyte-depleted mice, whereas proliferation of IC in the monocyte-depleted mice was 45% less than that in the normal mice. It was concluded that: cell proliferation of PAM is a significant local source of PAM, and division of cells in the interstitium could not be evaluated as a source of PAM due to the heterogenous nature of the cell types which comprise this population of cells. This study established that cell division of "free" PAM can be a significant local source of PAM and raises questions concerning the nature of the interstitial source of PAM.
The association constant and the maximal binding capacity for calcium, magnesium and strontium to human serum proteins were determined using a wide concentration range by a dialysis technique. The association curves are similar for these elements. Each curve may be subdivided in three parts: the first would correspond to the subfraction tightly bound to protein, the second one shows a linear design implying the association of the element to different binding points which have the same association constant, and the third part shows the saturation of proteins, which is achieved by alkaline-earth concentration about 9 times higher than the physiological ones.
The use of strontium 90 has proved to be efficient and practical, because handy, and permitting short treatment, not only, to cure benign superficial tumors and, as reported in this study, of pre-cancerous lesions such as actinic keratosis, Bowen's disease of the skin but also some carefully chosen cases of superficial carcinomas. Hundred lesions have been so treated and followed for 3 years; two only have relapsed. The cosmetic result has been excellent in 80 p. 100.
Because of the polymorphism of osteogenic sarcomas, examination of a biopsy specimen, which is necessarily small, cannot give an accurate evaluation of the differentiation of the whole tumor. Therefore, a test which provides an overall assessment of the functional capacity of the tumor is needed. For the last ten years, we have been using 85 strontium, which has a metabolism similar to that of calcium and radioactive characteristics that allow external measurements. With this isotope, classification of osteogenic sarcomas is more accurate, ensuring better therapeutic trials.
Electrical and mechanical activities of frog skeletal muscle fibres were simultaneously investigated under conditions which allow the development of a strontium permeability. It was shown that the contraction elicited by a long lasting Sr response depends upon two mechanisms: a potential dependent one, and a mechanism which is related to the entry of Sr ions into the cell through the tubular membrane.
The authors explored the statics of Ca2+ and Sr2+ sorption from a saline, imitating the salt (mineral) composition of the blood plasma, and from blood plasma. As the plasma concentration was raised, there was a consistent decrease in ion sorption of KU = 2 X 8 cationite characteristic for M2+ complex formation in solution. Conventional constants for formation of complex compounds and mole proportions (%) of free (M2+) and complex forms (MLx-) metals were calculated. The time course of calcium and strontium sorption on KU = 2 X 8 ion-exchange resin from saline and blood plasma was studied. It was discovered that sorption from saline proceeded according to the externally diffusion kinetics type, whereas sorption from plasma according to the mixed type of the ion-exchange kinetics. The kinetic ratios were calculated for the indicated versions of sorption experiments. The mechanisms of sorption found in model experiments were extrapolated to dog experiments with blood decalcination, which supported the adequacy of experimental hemosorption under consideration.
The phase II clinical trial of a strontium (89Sr) chloride agent (SMS. 2P) was performed in 9 patients with painful bone metastases secondary to prostate cancer. After an intravenous administration, 89Sr circulated in the plasma and was rapidly cleared. Urinary excretion varied widely among the patients. No serious acute side effects were observed. A mild transient increase in pain was reported by 4 patients 2-4 days after administration, two of whom complained of mild nausea or vomiting. All symptoms improved and never became a clinical problem. There were some abnormal hematological parameters. In particular, a decrease in the platelet level seemed to be a marrow suppression due to 89Sr irradiation. It is difficult to discriminate between the effects of 89Sr and the progress of the disease using tumor markers. The pain level improved within 2 weeks after administration and the effect continued for at least 8 weeks, which improved the quality of life for these patients.
Strontium-89 is a beta emitting radioisotope, avidly taken up by osteoblastic metastatic prostatic cancer. In both open and controlled studies, it has been shown to palliate metastatic pain effectively. It is as effective as conventional radiotherapy in palliation of the primary site(s) of pain, but in addition, it seems to delay pain progression. Its role is confined to palliation of pain in the absence of actual or impending complications (cord compression or pathological fractures). Bone marrow suppression makes it unsuitable for myelosuppressed patients. Cost is the main limitation to its use. It is a useful alternative to hemibody radiotherapy and to local treatment in selected patients. Its use in other tumour types (especially breast cancer) is currently under investigation. Trials investigating its use to delay onset of pain in symptom free relapsing patients should be considered.
For long-term pharmacokinetic studies in humans as well as in experimental animals, an analysis of strontium (Sr) with a low detection limit and high sensitivity is necessary. The data presented here describe the optimization of the furnace program and sample handling for measuring Sr in plasma by using graphite furnace atomic absorption spectrophotometry. The method was validated and applied to studies on the pharmacokinetics of SrCl2 in humans and rats. Calibration curves were linear up to 57.1 nmol/L. The limit of detection and lower limit of quantification were 0.21 and 0.57 nmol/L, respectively. Reciprocal sensitivity was 0.53 nmol/L Sr at A = 0.0044. The intraassay precision was 2.2%, 1.5%, and 1.1% (n = 6) at 4.57, 22.7, and 49.2 nmol/L Sr, respectively. At these concentrations, the interassay precision and recovery were 0.7%, 1.5%, and 1.8% and 100.4%, 99.1%, and 100.6% (n = 12), respectively. The endogenous Sr concentration in human plasma samples was 0.27 +/- 0.07 mumol/L (n = 18). Pharmacokinetic studies in a human volunteer and in rats demonstrated that this procedure was suited for measuring low Sr concentrations and was applicable to small sample volumes.
An initial assessment of treatment of chronic osteomyelitis in 16 adults with Strontium 85 is presented. A dose 3.5-5 times greater than standard scintigraphic one was administered. In 3 cases the dose has been repeated because of the persistence of infection. The radionuclide was well tolerated. In 14 cases ceasing of osteomyelitis have been achieved. Laboratory tests showed no abnormalities.