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Isotopic diversity as an unexplored mind-matter dimension.

The existence of several stable isotopes for most chemical elements is a well known and widely used fact of chemistry. Nevertheless, despite all the attention given to the stable and radioactive isotopes of individual elements, there have been very few, if any, attempts to look at isotopicity as a single phenomenon in its own right. Some possible links between isotopicity and various structural and functional levels of organization of the material and informational realm are put forward in this article, which presents isotopicity as an independent and informationally active level of spontaneous pattern formation and self-organization, giving a flexible link between morphogenetic potentialia and the microscopic operational level of physico-chemical processing. A dynamical parallel is drawn between Anderson localization induced by an isotopic disorder and holographic mental processing interpretable as self-focusing of mental patterns and spontaneous creativity.

Biology↗

Ferrokinetic studies with stable isotopes as tracers.

A methodology for ferrokinetic studies based on the administration of iron stable isotopes was developed. Fractional plasma clearance and intestinal iron absorption in rabbits were determined using the double tracer technique. Three rabbits were given 58Fe solution intravenously and about 40 min later 57Fe solution orally. Blood samples were drawn at different times following administration. The analysis of the single iron isotopes content in plasma samples was made by proton nuclear activation. The results were compared with those obtained from the administration, to the same rabbits, of the radioactive isotopes 55Fe and 59Fe. The agreement was found to be satisfactory.

Animals↗

Long-term clinical outcome of phase IIb clinical trial of percutaneous injection with holmium-166/chitosan complex (Milican) for the treatment of small hepatocellular carcinoma.

PURPOSE: The purpose of this study was to evaluate the long-term tumor response after phase IIb clinical study and the safety of percutaneous holmium-166 ((166)Ho)/chitosan complex injection (PHI) therapy for small hepatocellular carcinoma as a local ablative treatment. (166)Ho is a radioactive isotope derived from natural holmium-165. We developed a (166)Ho/chitosan complex (Milican, Dong Wha Pharmaceutical Co., Seoul, Korea) using chitosan as a vehicle to retain the radioactive material within the tumor. EXPERIMENTAL DESIGN: Forty patients with single hepatocellular carcinoma < 3 cm in maximal diameter were enrolled in this study. The patients either had refused surgery or were poor surgical candidates and were treated with only single session of PHI. RESULTS: Two months after PHI, complete tumor necrosis was achieved in 31 of 40 patients (77.5%) with hepatocellular carcinoma lesions < 3 cm and in 11 of 12 patients (91.7%) with hepatocellular carcinoma < 2 cm. Tumors recurred in 28 patients during the long-term follow-up period, of which 24 recurred at another intrahepatic site. The 1-year and 2-year cumulative local recurrence rates were 18.5% and 34.9%, respectively. The survival rates at 1, 2, and 3 years were 87.2%, 71.8%, and 65.3%, respectively. Transient bone marrow depression was serious adverse event requiring hospitalization in two patients. CONCLUSIONS: PHI was found to be a safe and novel local ablative procedure for the treatment of small hepatocellular carcinoma and could be used as a bridge to transplantation. A phase III randomized active control trial is clearly warranted among a larger study population.

Administration, Cutaneous↗

Isotope scanning of brain tumors in children.

A total of 31 brain tumors (21 verified histologically, 10 by clinical and neuroradiologic methods) in children aged from 7 months to 13 years were investigated by scintigraphy with 99mTc as a radioactive isotope tracer. There were 16 supratentorial and 15 infratentorial tumors. The supratentorial tumors were detected in 88%, and the infratentorial in 13%, of case by brain isotope scanning. The advantages and disadvantages of the method are discussed.

Astrocytoma↗

Metabolic studies on connective tissue collagens in bone and tendon of adjuvant arthritic rat.

The metabolic alterations in the matrix of connective tissue collagen were investigated in bone and tendon of rats with adjuvant-induced arthritis. Adjuvant arthritis was induced in rats with the immunization of Freund's adjuvant containing heat-killed Mycobacterium tuberculosis. The changes in the metabolism of collagen were studied using radioactive isotopic measurements with (3H)-proline. Tissue specimens were fractionated individually into soluble and insoluble collagens. The synthesis of collagen was examined by measuring the total collagen content and the radioactivity of (3H)-hydroxyproline in soluble collagen fraction within 24 hours after the administration of tritiated proline. The conversion of soluble to insoluble collagen was analyzed by measuring the radioactivity of (3H)-hydroxyproline in both soluble and insoluble collagens. The catabolism of soluble and insoluble collagens was studied by estimating the radioactivity of urinary (3H)-hydroxyproline 24 hours after the injection of tritiated proline. It was observed that the total collagen content and the total radioactivity of (3H)-hydroxyproline in bone and tendon were decreased significantly in adjuvant arthritic rats. The specific and total radioactivities of (3H)-hydroxyproline in soluble collagen were found to be reduced, indicating the decreased de novo synthesis of collagen during the diseased state. The conversion of soluble to insoluble collagen was impaired in tissues as evidenced by the increased content of soluble collagen in arthritic disease. In addition, an enhanced excretion of hydroxyproline was found in urine of arthritic rats, indicating the increased degradation of collagen in arthritic disease. These observations could, therefore, explain in part the changes in synthesis and degradation of collagen in bone and tendon during the development of experimentally induced adjuvant arthritis in rats.

Animals↗

Comparison of pathways of copper metabolism in aorta and liver. A functional test of metallothionein.

Soluble fractions from chick liver and aorta were examined for copper-binding proteins. In liver a zinc-binding thionein appeared to be the major binding protein for copper. Aortic tissue contained only traces of this thionein protein. Unlike liver, moderate amounts of soluble copper in aorta showed no association with macromolecules. Chicks fed on copper-deficient diets for 8 days had one-third the liver copper concentrations of controls. Aortic copper concentration was decreased only slightly, but the activity of lysyl oxidase, a copper-dependent enzyme in aorta, was decreased significantly. Treating the deficient chicks with CuSO4 (1 mg/kg) restored liver copper rapidly. The increase correlated with the binding of copper to a 10 000-mol.wt. component in the soluble fraction. Aortic copper concentrations responded much less to the CuSO4 treatment, but lysyl oxidase activity was again measurable in the tissue. Radioactive isotopes of copper bound almost exclusively to the 10 000-mol.wt. component in liver and to components of mol.wt. 30 000 or above in aorta. Hardly any of the administered radioactivity appeared with the 10 000-mol.wt. components in aorta, and none was found with unbound copper. The 30 000-mol.wt. components in aorta showed superoxide dismutase activity that was sensitive to NaCN. They also showed the highest specific activity of copper of any other aorta component. A clear distinction was seen between the metabolism of copper in liver and aortic tissues. Whereas a copper thionein, metallothionein, was a major component in the liver pathway, it is doubtful that this protein plays a major role in the intracellular metabolism of copper in aortic tissue.

Animals↗

Quantitative radioactive analysis of microleakage of four different retrograde fillings.

Sealing properties of four different retrograde filling materials were investigated in vitro. Radioactive isotopes were applied in the root canal, and leakage into an extraradicular fluid was measured at regular intervals. The method permitted repeated observation of the specimens over prolonged periods of time. Forty single-rooted human teeth were biomechanically instrumented and obturated using calcium-hydroxide paste. Following obturation, an apicectomy was performed and retrograde cavities were filled with four different materials: group 1, non gamma 2 amalgam (Amalcap); group 2, glass ionomer cement (Ketac Silver); group 3, calcium-hydroxide-based root canal sealer (Sealapex); group 4, composite resin (Palfique Light-S). After removal of the calcium hydroxide, the teeth were immersed in a fluid. An isotope solution was then placed in the root canals. Samples were taken from the fluid at 0, 3, 7, 28, 56, 105, 210, 285 and 376 days to determine the radioactivity. It was found that Sealapex and Palfique Light-S showed significantly less leakage than amalgam and glass ionomer cement, which had the highest apical leakage.

Analysis of Variance↗

Validation of use of 11,12-2H-labeled chenodeoxycholic acid in isotope dilution measurements of bile acid kinetics in man.

Chenodeoxycholic acid labeled with 2H in the 11 and positions was prepared by catalytic reduction of delta 11-12 unsaturated derivatives of cholic acid. To validate the use of this stable isotope for the determination of bile acid kinetics by isotope dilution, it was administered to seven normal male volunteers simultaneously with [24-14C]chenodeoxycholic acid. Bile was collected at regular intervals over the following 5 days, and the chenodeoxycholic acid pool size and fractional turnover rate were determined from the specific activity decay curve for 14C and from the isotopic abundance curve for 2H. Estimates of the pool size by both isotopes showed a correlation of r = 0.95 and similar precision. Synthesis rate, the product of pool size and fractional turnover rate, also showed good agreement (r = 0.97), Because previous investigations have shown that bile acids tagged with hydrogen isotopes at the 11 and 12 positions are stable in man, the present data suggest that 11, 12-2H-labeled bile acids may be used in place of radioactive isotopes for valid isotopic measurement of bile acid kinetics in healthy infants and children.

Adult↗

STUDIES ON INHIBITION OF INTESTINAL ABSORPTION OF RADIOACTIVE STRONTIUM. II. EFFECTS OF ADMINISTRATION OF SODIUM ALGINATE BY OROGASTRIC INTUBATION AND FEEDING.

A method is reported that enables selective suppression of absorption of radioactive strontium from ingested food material, permitting calcium to remain available to the body. Studies were carried out by measuring blood levels and bone uptake of Sr(89) and Ca(45) at different time intervals after orogastric intubation of rats. The addition of sodium alginate, derived from brown marine algae, to the radioactive isotopes increased the overall physiological discrimination against strontium by amounts up to 60% after 24 hours. This discrimination was further increased by feeding sodium alginate mixed with standard diet in the proportions of 20:80 and 30:70. The observed ratio was reduced by administration of sodium alginate from 0.25 to 0.09.Determination of the limiting dosage in rats is restricted to the amounts which rats will consume. In the event of an inadvertent release of radioactive strontium, human subjects probably could increase their intake of alginate at will, permitting a greater effectiveness of sodium alginate than could be obtained in experimental animals.

Absorption↗

[Cerebral circulation (measured by isotopes) and acid-base equilibrium of the cerebrospinal fluid during migraine].

In migraine patients a considerable metabolic disturbance characterised by a decrease in bicarbonate and an increase in lactate was demonstrated during the migrainous state. Measurements of the cerebral circulation were taken by means of radioactive isotope and showed a distinct decrease in blood supply to the entire brain during the migraine attack. Following forced hyperventilation during the attack-free interval a pathological reactivity with decreased blood flow was found in the hemisphere which had been indicated as the usual site of the migrainous pain.

Acid-Base Equilibrium↗

A new genetic test for familial hyperaldosteronism type I aids in the detection of curable hypertension.

In Familial Hyperaldosteronism Type I (FH-I, glucocorticoid-suppressible hyperaldosteronism), a curable form of hypertension inherited in an autosomal dominant fashion, the underlying genetic defect is a "hybrid gene" in which 11 beta-hydroxylase gene regulatory elements are fused to the coding region of the aldosterone synthase gene. The detection of this hybrid gene by Southern blotting is time consuming and involves the use of radioactive isotopes. We describe a new, long polymerase chain reaction-based method for detecting the hybrid gene which greatly reduces the time required to obtain a result, avoids exposure of laboratory workers to radioactive materials, and will thereby facilitate the screening of patients for the presence of FH-I.

Bartter Syndrome↗

129I in the oceans: origins and applications.

The quantity of the long lived (half-life 15.7 million years) radioactive isotope 129I in the pre-nuclear age ocean was approximately 100 kg. Various nuclear related activities, including weapons testing, nuclear fuel reprocessing, Chernobyl and other authorized or non-authorized dumping of radioactive waste have increased the ocean inventory of 129I by more than one order of magnitude. The most important of these sources are the direct marine discharges from the commercial reprocessing facilities at La Hague (France) and Sellafield (UK) which have discharged approximately 1640 kg in the English Channel, and approximately 720 kg in the Irish Sea, respectively. We discuss how this 129I can be used as both a 'pathway' and 'transit time' tracer in the North Atlantic and Arctic oceans, as well as a parameter for distinguishing between reprocessed and non-reprocessed nuclear waste in the ocean, and as a proxy for the transport and dilution of other soluble pollutants input to the North Sea.

Environmental Monitoring↗

[Nuclear medicine in vivo and functional imaging. Historical perspective].

Nuclear Medicine is the application of radioactive materials to the diagnosis and treatment of patients and the study of human disease. The field had its beginning with the discovery of radioactivity by H. Becquerel in 1896 and the tracer principle proposed in 1913 by G. de Hevesy who used a naturally occurring radioactive isotope of lead to obtain information regarding certain aspects of calcium metabolism in plants. The actual development is more recent. F. and I. Joliot-Curie just after the discovery of the artificial radioactivity predicted in their visionary Nobel conference in 1935 the future applications of radioisotopes in biology and medicine. The development of Nuclear Medicine was made possible by the possibility of producing routinely the radioisotopes after World War II and by the development of suitable detectors: moving detector devices (scanners) then gamma cameras after 1957. Nuclear Imaging is today a unique tool for the in vivo investigation of the biochemical functioning of an organ. Two techniques are in rapid development, SPECT (single photon emission computed tomography) and PET (positron emission tomography).

History, 19th Century↗

[Cerebral blood flow (measured by means of isotopes) and base-acid-equilibrium of the CSF in migraine (author's transl)].

In migraine patients a considerable metabolic disturbance characterised by a decrease in bicarbonate and in increase in lactate was demonstrated during the migrainous status. Measurements of the cerebral circulation were taken by means of radioactive isotopes and showed a distinct decrease in blood supply to the entire brain during the migraine attack. Following forced hyperventilation during the attack-free interval a pathological reactivity with decreased blood flow was found in the hemisphere which had been indicated as the usual site of the migrainous pain.

Acid-Base Equilibrium↗

Radioisotopic evaluation of the thyroid and the parathyroids.

Since the inception of the discipline of nuclear medicine, thyroid evaluation and therapy with radioactive isotopes have remained an important and constant component of thyroidology. Parathyroid scintigraphy with 201Tl/99mTc subtraction has been a more recent and also very useful addition in the assessment of hyperparathyroidism, particularly at reoperation. The radioactive iodine uptake test gives important metabolic information on thyroid function in such diverse disease states as hyperthyroidism, hypothyroidism, the thyroiditides, and thyroid carcinoma. Thyroid scintigraphy is also a key contributor to the assessment of patients with hyperthyroidism or with single versus multiple thyroid nodules, those with a history of head and neck irradiation during childhood, and those requiring diagnostic follow-up studies with 131I after total thyroidectomy for differentiated thyroid carcinoma. Each of these topics is reviewed and expanded on in this article, with a diversity of illustrative scans provided to complement the discussion.

Adult↗

Prediction of kidney mercury content by isotope techniques.

A 61-year-old female patient accidentally aspirated liquid mercury during a medically ordered diagnostic procedure. To develop animal-based guidelines, liquid mercury was introduced into the lungs of four dogs. Based on the study of these animals, a method of predicting the kidney inorganic mercury burden was developed using radioactive isotope dilution techniques. It was further demonstrated in dogs that oral administration of dimercaptopropane sulfonate (DMPS) increased mercury excretion and reduced the kidney burden. A rat experiment was performed permitting a statistical evaluation of the assumptions basic to the use of the method. The method was applied to the patient with the result that the kidney inorganic mercury burden was predicted to be 28.1 mg, 8 months after the accident. Treatment with DMPS increased urinary excretion and the post-treatment kidney burden was estimated at 19.6 mg Hg. Inasmuch as the radioactive dose to the subject may be kept at a negligible level and because sensitive methods exist for measurement of radioactive and stable mercury concentrations, the technique may be applicable in special cases to the estimation of kidney inorganic mercury burdens incurred by industrial exposure.

Animals↗

Determination of biokinetic parameters for ingestion of radionuclides of zirconium in animals using stable tracers.

Exposure to the radioactive isotope 95Zr, as in nuclear accidents, and to stable zirconium, due to its use in industry, has increased the interest in the biokinetics of this element. Information has been derived mainly from tests performed on animals by means of radioactive tracers. Due to the fact that extrapolation from animals to humans is always open to question, there is an increasing need of a methodology which allows data to be obtained directly from humans. The use of stable tracers, being ethically justifiable, is a powerful tool for providing this information. As two tracers of the same element must be utilized in order to evaluate gut absorption, an analytical technique which is capable of distinguishing and measuring simultaneously different isotopes of zirconium in biological samples is required. Preliminary tests on laboratory animals were performed in order to assess the feasibility of the double tracer technique combined with proton activation analysis.

Animals↗

An investigation of the effect of radioactive labeling of DNA on excision repair in UV-irradiated human fibroblasts.

Previous studies on the kinetics of thymine dimer excision and unscheduled DNA synthesis in UV-irradiated human fibroblasts showed a significant discrepancy in these two parameters (Ehmann et al., 1978. Biophys. J. 22: 249). In the present study we have investigated the effect of the level of the radioactive isotope used for labeling cells on the kinetics of a parameter that directly measures thymine dimer excision. We find no significant differences in the kinetics of this parameter in cells lightly or heavily labeled with radioactive thymidine.

Carbon Radioisotopes↗