Doses Of Cobalt Research Articles

Ternary iron-cobalt silicide fabricated by ion beam synthesis

Ternary silicide layers were fabricated by the implantation of iron and cobalt into (100) silicon wafers. Two sets of samples with different iron to cobalt ratios were prepared, with cobalt being implanted first followed by iron in the first set, and the implantation order being reversed for the second set. In all cases a total Fe + Co dose of 5 × 10 17 cm −2 was used. The structural properties of the synthesised layers were assessed by Rutherford backscattering spectrometry (RBS) and cross-sectional transmission electron microscopy (XTEM). Our results indicate that for the samples where cobalt was implanted first epitaxial layers are formed after implantation. However, when iron was implanted first the layers are non-crystalline. For the samples with iron implanted frrst no significant improvement in crystal quality was observed with increasing anneal temperature. However, for those samples where cobalt was implanted first we observed a strong dependence of the crystal quality on the annealing temperature. For the samples with cobalt doses ≥ 2.5 × 10 17 cm −2, where cobalt was implanted first, segregation of iron and cobalt within the synthesised layer is observed.

Taxol Sensitizes Human Ovarian Cancer Cells to Radiation

Taxol is an exciting antineoplastic agent with a novel mechanism of action. This study was designed to explore the potential use of taxol as a radiation sensitizer. Three human ovarian cancer cell lines were used: BG-1, SKOV-3, and OVCAR-3. These cell lines were treated in the proliferative and confluent state with taxol doses of 0.0001X, 0.0005X, 0.001X, 0.005X, and 0.01X peak plasma concentration of taxol for 90 min and then irradiated either 24 or 48 hr later. Doses of cobalt were 0, 2, 5, 8, and 10 Gy. ATP bioluminescence assays were performed on Day 7 after irradiation. Survival data was fit to the linear-quadratic model and mean inactivation dose D was calculated. Data analysis with t test and analysis of variance was performed. Taxol was found to have a significant radiosensitizing effect on all cell lines. Proliferating cells were more sensitive to taxol, radiation, and the combination than confluent cells. Treatment of proliferating cells with taxol 48 hr prior to irradiation had a greater radiosensitizing effect than treatment 24 hr prior to irradiation. In summary, taxol is a potent radiosensitizer in ovarian cancer cell lines and should be considered for further study.

The effects of single and fractionated doses of Cobalt 60 gamma radiation on the OM431 human ocular melanoma cell line

The effects of single and fractionated doses of Cobalt 60 gamma radiation on the OM431 human ocular melanoma cell line

The use of ATP bioluminescence assay and flow cytometry in predicting radiosensitivity of uterine cancer cell lines: Correlation of radiotoxicity and cell cycle kinetics

Radiotherapy remains an important part of uterine cancer treatment. This study was designed to evaluate the potential of the ATP bioluminescence assay and flow cytometry for predicting radiosensitivity. Correlation of these two modalities revealed important insights into the relationship of radiotoxicity and cell kinetic effects. Six human uterine cancer cell lines were used: AE7, ECC1, HEC1A, HEC1B, AN3, and SKUT1B. Doses of cobalt 60 were 0, 1, 2, 5, 8, and 10 Gy. The ATP bioluminescence assays were performed on Day 7. Cell samples were taken at 0, 24, 48, 72, 96, and 168 hr for flow cytometry. The linear-quadratic model was used to fit survival data and mean inactivation dose D ̄ was calculated. Among parameters such as D ̄ , α and β coefficients, and surviving fraction at 2 Gy (SF2), both D ̄ and SF2 correlated best with survival data. Radiation effects on the cell cycle did not correlate with D ̄ and revealed two distinct patterns: either a G1 accumulation with mild G2 block or a G1 depletion and severe G2 block. The S cells consistently demonstrated a biphasic pattern with an initial reduction followed by an accumulation. In summary, the ATP assay was shown to have potential in the study of radiosensitivity. Radiation-induced cell kinetics appeared to vary with intrinsic cellular differences and, thus, could not be used to predict radiosensitivity.

Alteration in myelin-associated proteins following spinal cord irradiation in guinea pigs

The aim of this study was to investigate the pathological and cellular basis for radiation-induced myelopathy in guinea pigs by monitoring biochemical alterations in levels of myelin basic protein and 2′,3′-cyclic nucleotide phosphohydrolase. Guinea pigs were irradiated to the lumbar region with various doses of neutrons or cobalt y irradiation. The ED 50s for paralysis were 17.2 Gy and 67.5 Gy for neutron and cobalt irradiation, respectively, and was histologically associated with demyelination. In spinal cords taken from animals at the onset of paralysis myelin basic protein levels were decreased in direct relationship to the radiation dose. The lowest doses to cause paralysis led to a 25% decrease in MBP levels. In a separate experiment, alterations in MBP were measured in the spinal cords over the time period leading up to paralysis. Surprisingly, decreases in MBP were found immediately after the end of the 4 week irradiation period. These early changes in MBP were not markedly dose dependent and occurred with nonparalyzing doses. Dose-dependent decreases were found only just before the onset of paralysis. CNPase activity measured in the same specimens showed changes that were essentially similar to those for MBP. In the CSF, MBP levels were essentially constant until onset of paralysis. This study showed that demyelination, as assessed by the levels of the myelin-associated proteins MBP and CNPase, can occur soon after spinal cord irradiation but that profound dose-dependant changes are seen only immediately preceding the onset of paralysis. Although increases in MBP in the CSF were associated with the onset of radiation-induced myelopathy, its assay is unlikely to predict this complication of irradiation.

Formation of CoSi 2 in SIMOX wafers by high dose cobalt implantation

SIMOX (separation by implanted oxygen) wafers were implanted with high doses of cobalt and annealed at high temperature in order to study the formation of buried single-crystal CoSi 2 layers in this material. For this study SIMOX wafers of (100) oriented silicon were implanted at 100–200 KeV with doses of 1.2–2.0×10 17 Co + cmsu−2, and annealed in a rapid thermal processor or tube furnace. As-implanted and annealed samples were analyzed by Rutherford backscattering with channeling spectroscopy (RBS), cross-sectional transmission electron microscopy (XTEM), secondary ion mass spectroscopy, and the van der Pauw technique. The best buried CoSi 2 layers were obtained at an implantation energy of 100 KeV and by subsequent rapid thermal annealing. RBS minimum yields of approximately 6% were obtained for the buried layer, which is the same as that reported for bulk (100) silicon. The measured resistivity of 15 μω cm and XTEM confirmed the continuity of the layer. Buried CoSi 2 layers were successfully produced up to an implantation energy of 180 keV. However, as the energy was increased the quality of the CoSi 2 layer degraded, with minimum yields increasing to 24% at 180 keV, and with a corresponding degradation in the minimum yields in the top silicon layer. At 200 keV a buried epitaxial layer was not produced. The degradation of crystal quality with ion implantation energy and the failure to produce a buried layer at 200 keV are discussed.

Analysis of the structure and defects in heteroepitaxial Si/CoSi 2/Si layers produced by ion beam synthesis and rapid thermal annealing

The effects of rapid thermal annealing (RTA) on the microstructure and electrical properties of ion-beam-synthesized silicide layers fabricated using cobalt doses of 7×10 17, 5×10 17 and 1.5×10 17 cm −2 at an energy of 200 KeV have been studied. For all three doses, increasing RTA temperature leads to the chemical segregation of the implanted cobalt—via the thermodynamically controlled dissolution of the small CoSi 2 precipitates in the wings of the distribution. Likewise, increasing the anneal temperature affects the removal of defects lying on Si{311} lattice planes, which are created by an excess of silicon self-interstitials. For the two highest doses, the phase transformation CoSi→ CoSi 2 is also facilitated by increasing anneal temperature. In all cases, it is found that the resistivity and crystallinity of the layers are critically dependent on the Co:Si ratio, with high quality low resistivity layers only being attained when this is close to 1:2, i.e. CoSi 2. After RTA at 1000 °C for 5 s, stoichiometric CoSi 2 layers were achieved for all doses, with layer thicknesses ranging from 600 to 18000 Å. The value of resistivity and crystallinity obtained for the medium dose specimen (5 × 10 17 cm −) were close to those achieved by conventional furnace annealing, with those for the higher and lower doses being slightly higher.

Cobalt stimulates carotid body chemoreceptors

Because cobalt administration is known to elicit erythropoietin response, it is a reasonable hypothesis that cobalt would also stimulate the O2-sensing process in the peripheral chemoreceptors. We tested this hypothesis by measuring the effects of cobalt chloride on carotid chemosensory fibers in pentobarbital-anesthetized cats that were paralyzed and artificially ventilated. Responses of carotid chemoreceptor afferents to graded doses of cobalt given by intra-arterial injections (0.08-2.10 mumols) were measured at constant blood gases. Responses of the same chemoreceptor afferents to hypoxia, before and after a saturation dose of cobalt, were measured. In two experiments carotid body tissue PO2 was also simultaneously measured. The chemosensory fibers showed prolonged excitation after a brief period of inhibition subsequent to cobalt administration. The stimulatory effect showed a dose-dependent saturation response. Cobalt augmented rather than blocked carotid chemoreceptor response to hypoxia. The effect of cobalt was not mediated by tissue PO2. These results are consistent with the hypothesis that cobalt stimulates the O2-sensing mechanism, although a direct effect of cobalt on the excitability of the chemosensory terminal remains a possibility.

The effect of cobalt on mitochondrial ATP-production in the rat myocardium and skeletal muscle

Cobalt has been shown to accumulate in the myocardium of uraemic patients and has been suggested as a myocardial toxin inhibiting mitochondrial respiration. In order to study the cellular effects of cobalt exposure three groups of rats (n = 12 per group) were fed a diet containing 12% protein without supplementation or with 20 mg and 40 mg CoSO4 7 H2O/kg body weight/day respectively. After 8 weeks the hearts and soleus muscles were removed. Cobalt in tissues and in four cell fractions were analysed with neutron-activation analysis (ng/g wet weight and ng/mg protein respectively). Mitochondrial respiration was analysed as ATP-production rate using pyruvate + malate and palmitoyl-carnitine + malate as substrate. The ATP-production from pyruvate + malate was unchanged in both heart and skeletal muscle in the exposed animals. With palmitate as substrate, the heart muscle showed a slightly lower ATP-production rate (p less than 0.05) after the 20 mg cobalt dose, but the rate was unchanged in the group with higher cobalt intake. No changes in ATP-production rate from palmitate was observed in soleus muscle. The microsomal (100,000 g) fraction in the myocardial cells contained significantly higher cobalt concentrations compared to the mitochondrial fraction in both the unexposed (1.4 ng/mg protein vs 0.19, p less than 0.05) and exposed rats (53.4 ng/mg protein vs 13.2, p less than 0.005). In conclusion, cobalt showed a large accumulation in myocardial cells, without significant effects on mitochondrial ATP-formation rate from oxidation of pyruvate or palmitate and with the highest cobalt content contained in the microsomal (100,000 g) fraction.

Therapeutic effectiveness of 2,3,2 tet, cyclam and EDTA in toads exposed to lethal doses of nickel and cobalt

1. 1. In the course of the present investigation, three chelating agents (2,3,2 tet, cyclam or EDTA) were tested for their therapeutic effect on nickel and cobalt poisoned toad. 2. 2. Our results showed that EDTA appears to be superior to the two other ligands, which have been proved to be chemical ligands for Ni and Co in vitro. 3. 3. EDTA was able to prevent disturbances in the activities of serum aspartate and alanine amino-transferases, alkaline phosphatase, total protein, urea, uric acid and blood glucose level. 4. 4. Our results suggest caution in the use of 2,3,2 tet or cyclam in human Ni and Co intoxication.

Grazing management studies with Australian cashmere goats. 4. Cobalt supplementation and intestinal parasite burdens in sheep and goats in south-eastern Queensland

A flock of 32 weaner wether sheep (Border Leicester x Merino) and 32 weaner male goats (Australian cashmere) were grazed (37 animals/ha) on a common pasture of N-fertilised pangola grass from early March until June. One half of each group (16 animals) was supplemented with cobalt, and one half of each of these groups (8 animals) was dosed with approximately 500 infective helminth larvae at 2-week intervals throughout the trial. The final treatment was a drenching regime for one half (4 animals) of each of the above groups, levamisole (Nilverm) at 0, 2, 4 and 7 weeks and rafoxanide (Ranide) at 2-week intervals thereafter. There was no significant effect (P>0.05) of either cobalt supplementation or dosing with larvae on liveweight change, parasite egg concentrations in faeces or daily parasite egg excretion. Sheep gained significantly (P<0.05) more weight (50 g/day) than goats (31 g/day) in the first 7 weeks, and sheep also responded significantly (P<0.05) to drenching in this period whilst goats did not. In the second 8 week period, goats and sheep lost weight at a similar rate (-11 g/day), and both sheep and goats responded significantly (P<0.05) to drenching. The drenching program significantly (P<0.05) decreased faecal egg counts in sheep but not in goats. Undrenched sheep generally had higher concentrations of eggs in faeces than did undrenched goats, and with the exception of 1 sampling period, sheep also excreted significantly (P<0.05) more faecal eggs daily than goats. Undrenched sheep had significantly (P<0.05) lower haemoglobin concentrations in blood (82 gL) than drenched sheep (97 g/L). Undrenched goats also had lower blood haemoglobin concentrations (88 g/L) than did drenched goats (92 g/L). Cobalt supplementation did not exacerbate intestinal parasite burdens in either sheep or goats, and whilst goats did not appear to be more susceptible to intestinal parasites than sheep, the drenching strategies used for sheep were not effective in these goats.

Duration of effective benefit from administration of graded oral doses of cobalt to sheep.

The rapidity and duration of the response of sheep to graded oral doses of cobalt, given as the sulphate or as a cobalt-supplemented anthelmintic Panacur SC, was assessed by the determination of serum vitamin B12 and methylmalonic acid concentrations. The rapidity of the response to the treatments, which ranged from 1 to 250 mg cobalt, was unaffected by dose rate but the effective duration was dose related. There was some evidence of a cumulative effect from repeat treatments of the anthelmintic at three weekly intervals. It is suggested that the optimum inclusion rate for cobalt in anthelmintics lies within the range 21 to 100 mg/treatment.

Trace Metal Interactions in Vivo: Inorganic Cobalt Enhances Urinary Copper Excretion without Producing an Associated Zincuresis in Rats

The effects of cobalt chloride on copper and zinc metabolism in male Sprague-Dawley rats were examined. These effects were compared with those of penicillamine, a chelating agent utilized in the therapy of the genetic abnormality of copper metabolism in humans, Wilson's disease. Cobalt elicited an increased (approximately 4-fold) urinary excretion of copper lasting through 72 h following a single cobalt dose. In contrast to the marked increase in urinary zinc excretion produced by penicillamine, cobalt greatly reduced (approximately 75%) zinc output in urine. Tissue copper and zinc concentrations were measured after treatment with cobalt at doses ranging from 12 to 60 mg/kg body weight. Substantially reduced (approximately 25%) renal copper concentration was observed at 1 and 3 d after cobalt administration. In addition, cobalt produced a concurrent dose-dependent elevation (up to 1.6-fold) in hepatic zinc concentration. Cytosolic zinc was eluted from a Sephadex G-75 column in the molecular weight region associated with metallothionein. Time-dependent induction of metallothionein concentration (10-fold) in liver by cobalt was confirmed by the cadmium/hemoglobin affinity assay. The ability of inorganic cobalt to elevate zinc concentration in liver and produce increased urinary copper excretion without the zincuresis that normally accompanies penicillamine administration represents a newly defined biological property of this essential trace metal.

Conformation therapy to improve the irradiation of the spinal axis.

Techniques for the irradiation of the spine have remained largely unchanged since the introduction of megavoltage therapy. The main disadvantages of these techniques are the inhomogeneous dose distribution and the problems associated with field joins. The tracking method of conformation therapy employs a short field length and translates the patient through the beam on the couch of a computer controlled treatment unit. Dose uniformity along the spinal axis is achieved by controlling the speed at which the target travels through the radiation field. Treatment is given at standard source-axis distance (SAD) and the need for external shielding is eliminated by shaping the width of the field. The join with the cranial fields is independent of any skin marks, removing the risk of over- or under-dosage. Treatments are planned automatically from computed tomography (CT) information by an in-house planning system. The calculated doses have consistently shown good agreement with phantom measurements. Three cobalt dose distributions are presented and compared: a tracking treatment; a single posterior field, and two matched fields. The superiority of conformation therapy over the other commonly used treatment methods is clearly demonstrated.

Evaluation of the efficacy of trace element supplementation of an anthelmintic.

The efficacy of the selenium and cobalt contents of a trace element supplemented anthelmintic was evaluated in a series of trials with lambs in Scotland and Northern Ireland. The product was compared with other methods of supplementation and was found to be an adequate source of selenium when administered at monthly intervals. Its cobalt content was shown to be of some nutritional benefit on four of five sites but not as effective as the monthly 250 mg oral cobalt dose, vitamin B12 injection or intraruminal soluble glass bolus treatments also used. No growth responses were obtained and unsupplemented animals generally had an adequate cobalt and selenium status. No toxicity problems were encountered from either element.

Metabolism of 51Cr, 54Mn, 59Fe and 60Co in lactating dairy cows.

Different radionuclides which can be released by nuclear installations (Na2(51) CrO4 , 54MnCl2 , 59FeCl3 and 60CoCl2 ) were given to lactating dairy cows either orally or by intravenous (i.v.) injection. Excretion into feces and urine as well as secretion into milk were followed for several weeks. Distribution of activity in organs was determined at sacrifice 102 days after oral and 70 days after i.v. administration. After ingestion, excretion of chromate followed a three-term exponential function with half-lives of 0.88, 3.7 and 26 days. Intestinal absorption was on the order of 0.1-0.2%. About 63% of injected chromate was excreted into urine, about 18% into feces and about 3.6% into milk. Orally administered chromate was concentrated in liver, intestine and spleen. The transfer coefficient into milk was about 1 X 10(-5) days/1. Less than 1% of an ingested dose of manganese was absorbed. Excretion occurred mainly into feces and followed a three-term exponential function. Very little manganese was excreted into urine or secreted into milk. Manganese is concentrated in brain, pancreas, kidney and heart but the differences in concentration are small. The body burden is, therefore, mainly determined by manganese in muscle, skin and bone. The transfer coefficient of manganese into milk is about 3 X 10(-5). Excretion of iron into feces after oral administration follows a three-term exponential function with a small component having a half-life of 72 days. Intestinal absorption is on the order of 0.5-2% of the dose. After i.v. administration, 7% of the dose is excreted in the feces displaying two components of turnover. Very little iron is excreted into urine. Secretion into milk also follows a two-term exponential function. The transfer coefficient of iron into milk is about 3 X 10(-5). About 0.6% of an oral and about 94% of an i.v. dose were recovered from the cows at sacrifice. Most activity was present in blood, liver and spleen. Excretion of radiocobalt into feces after oral administration is described by a three-term exponential function, while excretion into milk and urine is described by two-term exponential functions. Long-lived components in urine and milk represent about 5-10% of the activity absorbed. Only 1-2% of an oral cobalt dose is absorbed and 0.05% of an oral and 5.85% of an i.v. dose is recovered from the cow at sacrifice where concentrations are highest in kidney and thyroid. The body burden depends mainly on cobalt in muscle, skin and bone. The transfer coefficient of cobalt into milk is about 7.5 X 10(-5).

Observations on pulmonary metastases in patients after single doses and multiple fractions of fast neutrons and cobalt-60 gamma rays

Pulmonary metastases have been irradiated with single and fractionated doses of fast neutrons and cobalt- 60 gamma rays. The response to radiation was measured on volume changes of the lesions and thus RBE values could be derived. A correlation was found between grading of the tumour and volume doubling time and also between RBE and volume doubling time. This suggests an advantage for high LET radiation of slowly growing, well differentiated tumours. Furthermore the RBE for multiple fractions tends to be higher than for single doses. Calculation of the N exponent of the Ellis formula indicated that hardly any shoulder exists when neutrons are applied.

Effect of vitamin B12b injections on the growth of young Merino sheep

In two experiments near Robe in the south-east of South Australia, on soil highly prone to the occurrence of cobalt deficiency in sheep, the effect of injections of vitamin B12b (hydroxocobalamin) on grossly cobalt-deficient weaner sheep and suckling lambs was compared with the effect of oral doses of cobalt as liquid drenches or ruminal pellets. All the supplements used were effective in treating cobalt-deficient weaned sheep or preventing the onset of cobalt deficiency in lambs. A single injection of vitamin B12b (1 mg), under the conditions of these experiments, satisfied the requirements of lambs for 14 weeks and cobalt-deficient weaner sheep for up to 40 weeks. The use of vitamin B12b in preventing or correcting cobalt deficiency in sheep in the field is discussed. Serum vitamin B12b concentration was not a reliable indicator of the vitamin B12b status of young sheep which had been given single injections of vitamin B12b. Vitamin B12b, deficiency in sheep was associated withdecreased concentrations of blood haemoglobin and of glucose, total proteins, urea and cholesterol in blood serum. The activities of serum aspartate transminase and alkaline phosphatase did not appear to be affected by the vitamin B12b status of the sheep.

Combination of radiotherapy and immunotherapy in the treatment of Lewis's tumour

Three groups of 6–8 week old male C 57 B1 6 × DBA2 F1 mice with transplanted Lewis tumour were irradiated by a single dose of Cobalt 60 localized on the tumour in association with intraperitoneal injections of BCG. When the animals were sacrificed, tumour parameters were determined: weight, surface area, volume and lung metastasis. When BCG was applied up to and including the 4th day following the end of the irradiation, tumour growth and the number of lung metastases were significantly decreased in comparison with the control group (P < 0·01). In all the groups where BCG treatment was started after the 4th day post-irradiation, there was no effect of BCG when compared with radiotherapy alone. This emphasizes the importance of timing in radiotherapy and immunotherapy association.

The Treatment of Refractory Anaemia of Chronic Renal Failure with Cobalt Chloride

Twelve anephric patients on maintenance haemodialysis received treatment with oral enteric coated cobalt chloride 25 to 50 mg daily. The change in haemoglobin concentration, and packed cell volume, are recorded and discussed with special reference to possible toxicity and mechanism of action of cobalt. Six of eight patients who completed the first course with cobalt chloride 50 mg daily for 12 weeks showed a significant rise in haemoglobin concentration of 26 to 70 per cent and a fall to near pre-therapeutic levels when cobalt was withdrawn. Evidence of a response was present within two months of starting treatment. Four patients showed a diminution in their blood transfusion requirements and three patients experienced a definite sense of increased well-being during treatment. One patient suffered from side effects of the drug and failed to complete the study because of gastrointestinal disturbance. The improvment in haemoglobin concentration was reproducible in four patients who were given second, and in one case third courses courses with varying doses of cobalt over differing periods of time. Serum cobalt levels tended to stabilize after two months continuous treatment to the therapeutic range of 40-100 mumg per 100 ml. A rapid fall in serum cobalt was seen on cessation of treatment. It is suggested that therapy with enteric coated cobalt chloride at a dose of between 25 and 50 mg per day has a definite place in the treatment of the refractory anaemia of chronic renal failure.