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PubMed1998

CuTira brachytherapy: a new combination of radioactive copper isotopes and the hypoxic cytotoxin, tirapazamine, for targeted tumor therapy.

We previously showed a significant enhancement of tirapazamine-induced cytotoxicity and DNA damage after binding with copper. This result suggests that conjugates of tirapazamine with radioactive copper, i.e., 64Cu and 67Cu, may offer potential for targeted therapy of a wide range of advanced stage tumors including a possible treatment for patients with solitary hepatocellular carcinoma by intrahepatic arterial infusion. Major supporting considerations include: (a) tirapazamine having a high selective toxicity against hypoxic cells; (b) the nature of radioactive decay of these copper isotopes and obtainable high specific activity; and (c) simple procedure for the production of copper-tirapazamine complex.

Brachytherapy↗
PubMedDate not supplied

Depleted and natural uranium: chemistry and toxicological effects.

Depleted uranium (DU) is a by-product from the chemical enrichment of naturally occurring uranium. Natural uranium is comprised of three radioactive isotopes: (238)U, (235)U, and (234)U. This enrichment process reduces the radioactivity of DU to roughly 30% of that of natural uranium. Nonmilitary uses of DU include counterweights in airplanes, shields against radiation in medical radiotherapy units and transport of radioactive isotopes. DU has also been used during wartime in heavy tank armor, armor-piercing bullets, and missiles, due to its desirable chemical properties coupled with its decreased radioactivity. DU weapons are used unreservedly by the armed forces. Chemically and toxicologically, DU behaves similarly to natural uranium metal. Although the effects of DU on human health are not easily discerned, they may be produced by both its chemical and radiological properties. DU can be toxic to many bodily systems, as presented in this review. Most importantly, normal functioning of the kidney, brain, liver, and heart can be affected by DU exposure. Numerous other systems can also be affected by DU exposure, and these are also reviewed. Despite the prevalence of DU usage in many applications, limited data exist regarding the toxicological consequences on human health. This review focuses on the chemistry, pharmacokinetics, and toxicological effects of depleted and natural uranium on several systems in the mammalian body. A section on risk assessment concludes the review.

Animals↗
PubMed1979

The use of ionising radiation for the treatment of injuries to flexor tendons and supporting ligaments in horses.

A technique was developed using radioactive isotopes as a source of radiation for the treatment of injuries to the superficial and deep flexor tendons and the associated ligaments in the horse. The treatment area was sub-divided so that different dosages could be applied over the limb as necessary. A plaster of Paris impression was taken of the whole area to be treated. In the isotope laboratory a plaster negative was made and loaded with the dose of radioactive isotope. The loaded cast was then strapped to the horse's limb for the calculated time, usually about three days. A total of 42 horses were treated and follow up information was obtained from 28. Twenty-five animals raced again; two relapsed before racing and one was destroyed with navicular disease. Ten of the 42 horses had been treated by firing before irradiation. Five of these returned to racing but the history of four of them was not known.

Animals↗
PubMed1999

Use of stable isotopes to study carbohydrate and fat metabolism at the whole-body level.

The present review discusses the advantages and limitations of using stable-isotope tracers to assess carbohydrate and fat metabolism at the whole-body level. One advantage of stable- (v. radioactive-) isotope tracers is the relative ease with which the location of a label within a molecule can be determined using selected-ion-monitoring GC-mass spectrometry (SIM-GC-MS). This technique minimizes potential problems due to label recycling, allows the use of multiple-labelled compounds simultaneously (e.g. to quantify glucose cycling), and perhaps most importantly, has led to the development of unique stable-isotope methods for, for example, quantifying gluconeogenesis. However, the limited sensitivity of SIM-GC-MS sometimes requires that relatively large amounts of a stable-isotope tracer be used, thus increasing cost and potentially altering metabolism. At least theoretically, stable- (or radioactive-) isotope tracers can also be used in conjunction with indirect calorimetry to estimate utilization of muscle glycogen or triacylglycerol stores, thus potentially circumventing the need to obtain muscle biopsies. These calculations, however, require certain critical assumptions, which if incorrect could lead to major errors in the values obtained. Despite such limitations, stable-isotope tracers provide a powerful and sometimes unique tool for investigating carbohydrate and fat metabolism at the whole-body level. With continuing advances in availability, instrumentation and methods, it is likely that stable-isotope tracers will become increasingly important in the immediate future.

Carbohydrate Metabolism↗
PubMed2004

The VITAL assay: a versatile fluorometric technique for assessing CTL- and NKT-mediated cytotoxicity against multiple targets in vitro and in vivo.

Assessment of cell-mediated toxicity has traditionally been achieved by measuring the specific activity of enriched effector cell populations against antigen-loaded target cells labeled with radioactive isotopes in vitro. Fluorometric techniques are viewed as a promising alternative to the use of radioactive isotopes for these analyses. Direct assessment of cytotoxicity in vivo can be achieved by monitoring survival of injected fluorescent targets relative to a differentially labeled internal control population without specific antigen. We have developed this approach, incorporating the use of multiple target cell populations labeled with different dyes so that cytotoxicity can be assessed against titrated doses of a given antigen, or against a range of different antigens, simultaneously. We show that this assay, referred to as the VITAL assay, can be used to assess cytotoxic activity of CTL and iNKT cells in vivo and in vitro. CTL responses measured in vivo could be correlated with antigen doses used in immunization strategies, and also with the size of specific CTL populations enumerated in the blood with fluorescent MHC/peptide tetramers. The VITAL assay is, therefore, a sensitive technique allowing analysis of complex multi-epitope responses.

Animals↗
PubMed1976

The association between systemically administered radioisotopes and subsequent malignant disease.

There is a long history recording the association of x radiation and the subsequent development of malignant tumors. For systematically administered isotopes this came into prominence when Martland discovered the association between cancer, particularly of the bone, and ingestion of radioactive isotopes by radium dial painters. This association was amplified by the development of cancer in patients given thorotrast as a contrast medium for diagnostic radiologic examination. Acute leukemia was reported 30 years ago in patients with polycythemia vera treated with 32P. Acute leukemia also occurs in patients with polycythemia vera treated only with phlebotomy or drugs. A controlled study is now underway to provide a more definite answer to question what is the incidence of acute leukemia in patients with polycythemia vera treated by phlebotomy alone, chlorambucil, or 32P. 131I for the treatment of hyperthyroidism probably does not induce cancer, but in the doses used for thyroid cancer there was an increased incidence of neoplasms (12/200 in one study). This was higher than the expected incidence of neoplasms. The doses of radioactive isotopes used currently for diagnostic purposes have not induced cancer, but it is difficult and probably impossible to verify this with absolute certainty.

Humans↗
PubMed1956

Radioisotopes for research on and control of mosquitos.

Practical applications of radioactive isotopes in medicine, science, and industry have multiplied enormously during the past five years. In this paper, the author attempts to gather what is known about the use of radioactive isotopes in the research on malaria control.The development of the uranium pile for large-scale production of radioisotopes and technical progress in the making of reliable electronic equipment have greatly contributed to the application of radioactive tracers in biological research. The present knowledge of radioisotopes in mosquito and in insecticide research is discussed.

Animals↗
PubMed1990

[Effect of clebopride on gastric emptying studied using a physiologic meal marked with Tc 99m colloid in subjects with non-ulcer dyspepsia].

The authors studied the action of clebopride on gastric emptying in subjects with non-ulcer dyspepsia by using radioactive isotopes. Eighteen subjects complaining of dyspeptic symptoms were studied in whom the tests undertaken had not shown organic lesions of the digestive tract. Tests with radioactive isotopes were performed before and after administration of clebopride (0.5 mg, three times daily for 15 days). In all patients gastric emptying time was normalized and gastric peristalsis became regular. In addition, in 85% of the patients, symptoms disappeared or were markedly reduced. Side effects requiring withdrawal of the drug were not observed. The above study, therefore, showed clebopride to be a useful drug for the treatment of non-ulcer dyspepsia, thus confirming data found in the literature.

Adult↗
PubMed1999

[Synthesis of tumor affinity label Yb-169- and Y-90- porphyrin complexes and animal experimental investigations with various Yb-169-porphyrins].

AIM: It should be shown, that it is possible to insert radioactive isotopes of Yb and Y into some selected porphyrins. Besides, first informations about the biodistribution of Yb-169-por-phyrin-complexes should be obtained. METHODS: Carrier added radioactive isotopes were used for the synthesis of the metal porphyrin complexes. The animal experiments were done with mamma carcinoma bearing mice. The activity of the organs was determined 5 and 24 h after i.v. injection in a well counter. RESULTS: Four Yb-169-porphyrin complexes and Y-90-porphyrin complexes could be synthesized in non-carrier-free form. This was verified by absorption spectra, TLC and HPLC. Depending on the complex, the average tumour/background ratios were between 2 and 20. CONCLUSION: The synthesized radioactive metal-porphyrin complexes showed a clear tumour-affinity which could be used for tumour scintigraphy or perhaps therapy if the synthesis is improved (goal: reduction of carrier, other radionuclides).

Animals↗
PubMed1997

Chromosome aberrations induced in human lymphocytes by U-235 fission neutrons. Part III: Evaluation of the effect of the induced alpha and beta activity on the chromosomal aberration yield.

AIM: Further experiments were performed to explain a difference in chromosomal aberration yield found between samples cultivated immediately after fission neutron irradiation and samples which were cultivated with 96 h delay after irradiation. MATERIAL AND METHOD: Human peripheral blood samples were irradiated in mixed fission neutron/gamma field (1800 s) and biological effect assessed in the mean of analysis of unstable chromosome aberrations with a time delay in culturing cells of 12, 24, 48, and 96 h. Additional measurements were performed on irradiated and blank blood samples with the aim to detect any increase in alpha and beta activity after fission neutron irradiation. No difference was found. Results were compared to theoretically calculated values of the alpha and beta activity released from natural radioactive isotopes. RESULT AND CONCLUSION: As a conclusion it is shown that in our experimental conditions the secondary effects resulting from nuclear transformations of natural or induced radioactive isotopes, recoil reactions and accompanying alpha, beta, and gamma radiation are not the reason for the increase observed in chromosomal aberration yield in blood samples cultured with a time delay of at least 24 hours.

Alpha Particles↗
PubMed1971

Microbial life at 90 C: the sulfur bacteria of Boulder Spring.

The physiology of the bacteria living in Boulder Spring (Yellowstone National Park) at 90 to 93 C was studied with radioactive isotope techniques under conditions approximating natural ones. Cover slips were immersed in the spring; after a fairly even, dense coating of bacteria had developed, these cover slips were incubated with radioactive isotopes under various conditions and then counted in a gas flow or liquid scintillation counter. Uptake of labeled compounds was virtually completely inhibited by formaldehyde, hydrochloric acid, and mercuric bichloride, and inhibition was also found with streptomycin and sodium azide. The water of Boulder Spring contains about 3 mug of sulfide per ml. Uptake of labeled compounds occurs only if sulfide or another reduced sulfur compound is present during incubation. The pH optimum for uptake of radioactive compounds by Boulder Spring bacteria is 9.2, a value near that of the natural spring water (8.9). Many experiments with a variety of compounds were performed to determine the temperature optimum for uptake of labeled compounds. The results with all the compounds were generally similar, with broad temperature optima between 80 and 90 C, and with significant uptake in boiling (93 C) but not in superheated water (97 C). The results show that the bacteria of Boulder Spring are able to function at the temperature of their environment, although they function better at temperatures somewhat lower. The fine structure of these bacteria has been studied by allowing bacteria in the spring to colonize glass slides or Mylar strips which were immediately fixed, and the bacteria were then embedded and sectioned. The cell envelope structure of these bacteria is quite different from that of other mesophilic or thermophilic bacteria. There is a very distinct plasma membrane, but no morphologically distinct peptidoglycan layer was seen outside of the plasma membrane. Instead, a rather thick diffuse layer was seen, within which a subunit structure was often distinctly visible, and connections frequently occurred between this outer layer and the plasma membrane. The thick outer layer usually consisted of two parts, the outer part of which was sometimes missing. Within the cells, structures resembling ribosomes were seen, and regions lacking electron density which probably contained deoxyribonucleic acid were also visible.

Acetates↗
PubMed2006

Adverse pregnancy outcomes in offspring of fathers working in biomedical research laboratories.

BACKGROUND: Laboratory work may constitute a possible health hazard for workers as well as for their offspring, and involves a wide range of exposures, such as organic solvents, carcinogenic agents, ionizing radiation, and/or microbiological agents. Adverse pregnancy outcomes in the offspring of male employees in biomedical research laboratories are examined. METHODS: Offspring to males employed 1970-1989 at four Swedish universities were identified via the Medical Birth Register (MBR), along with other pregnancy parameters. Offspring of fathers with laboratory work (n = 2,281) is considered exposed, and of non-laboratory employees unexposed (n = 1,909). Exposure data were obtained by questionnaires to research group leaders. Logistic regression analysis estimated odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Paternal laboratory work in general showed no statistically significant increased ORs concerning birth weight and/or gestational age, but work specifically with radioactive isotopes gave OR 1.8 (CI 1.0-3.2) for high birth weight and a relative risk of 1.2 (CI 1.0-1.4) for sex ratio (male/female). CONCLUSIONS: There was no clear association between periconceptional paternal laboratory work and adverse reproductive outcomes, but use of radioactive isotopes showed increased OR for high birth weight in offspring.

Adult↗
PubMed1993

Cryopreservation of periosteum for transplantation.

The concept of biological joint resurfacing has been widely studied, with encouraging results to date in both animal and human experiments. Most investigators have studied autograft tissue, however, in the clinical setting, situations might arise where autografting would not be suitable. We were therefore interested in developing a method of storing allograft periosteal tissue for biological joint resurfacing. A total of 192 periosteal grafts were harvested from 48 New Zealand White rabbits using sharp dissection (to include the cambium layer of progenitor cells). The free grafts were placed in a culture medium containing the cryopreservative dimethyl sulfoxide, then cooled at a controlled rate in a programmable freezer at rates of -0.5, -1.0, -2.0, or -10.0 degrees C/min. Viability of the grafts was assessed upon thawing after frozen storage for 8 days or 4 months using autoradiography and radioactive isotope uptake into newly synthesized proteins. Fresh, noncryopreserved and killed grafts were used as controls. A rate of cooling of -1.0 degrees C/min yielded viability results that were not significantly different from those of fresh controls. Furthermore, there was no change in viability as measured by radioactive isotope uptake over 4 months of storage. These results indicate that cryopreservation is a simple and efficient means of storing periosteal tissue for up to 4 months.

Animals↗
PubMed1975

Relationships between the exchange of calcium and phosphate in isolated fat-cells.

The uptake and the washout of 45Ca2+ and 32Pi is described in free fat-cells and whole epididymal fat-pads from fed rats. 2. In isolated fat-cells, the uptake of 45Ca2+ proceeds with an initial rapid phase of about 1 min duration, followed by a slower subsequent accumulation. In contrast with the rapid phase, the slow phase is inhibited by 2,4-dinitrophenol, warfarin, oligomycin and verapamil, shows saturation, and presumably represents transport across the plasma membrane. 3. The washout of 45Ca2+ from preloaded cells consists of a rapid (1 min) initial phase and a slow phase which is non-monoexponential, suggesting that the radioactive isotope is released from several cellular pools. 4. When Pi is omitted from the incubation medium, the slow phase of 45Ca uptake is almost abolished, and the washout of 45Ca from preloaded fat-cells is markedly accelerated. At elevated extracellular concentrations of Pi (2,4-6.2mM), the uptake of 45Ca is stimulated by 2-10-fold, and the release of the radioactive isotope from preloaded cells is inhibited. In whole epididymal fat-pads, variations in the extracellular concentration of Pi have no detectable effect on the uptake or the washout of 45Ca. 5. In isolated fat-cells, the accumulation of 32Pi is inhibited by 2,4-dinitrophenol or the omission of glucose from the incubation medium. In a Ca2+-depleted buffer, the uptake of 32Pi is diminished, and hyperosmolarity, which stimulates 45Ca uptake, also accelerates the accumulation of 32Pi. 6. It is concluded that in free fat-cells, the uptake and release of Ca2+ and Pi take place by closely interrelated processes, which are dependent on mitochondrial energy production.

Adipose Tissue↗