Application of an equilibrium-based model for diffusion barrier charcoal canisters in a small volume non-steady state radon chamber.

Radon in indoor air is often measured using activated charcoal in canisters. These are generally calibrated using large, humidity- and temperature-controlled radon chambers capable of maintaining a constant radon concentration over several days. Reliable and reproducible chambers are expensive and may be difficult to create and maintain. This study characterizes a small radon chamber in which Rn gas is allowed to build up over a period of several days for use in charcoal canister calibration and educational demonstrations, as well as various radon experiments using charcoal canisters. Predictive models have been developed that accurately describe radon gas kinetics in the charcoal canisters. Three models are available for kinetics in the small chamber with and without radon-adsorbing charcoal canisters. Presented here are both theoretical and semi-empirical applications of this equilibrium-based model of radon adsorption as applied to canisters in the small chamber. Several charcoal canister experiments in the small chamber with an equilibrium-based model of radon adsorption applied are reported. Results show that it is necessary to include a continuous radon monitor in the chamber during canister exposures, as the radon removal rate is highly variable. Furthermore, the presence of the canisters significantly decreases the amount of radon in the small chamber, especially when several canisters are present. It was found that canister response in the small chamber is largely consistent with the equilibrium-based model for both applications, with average errors of 1% for the theoretical application and -4% for the semi-empirical approach.

Evaluation of total effective dose due to certain environmentally placed naturally occurring radioactive materials using a procedural adaptation of RESRAD code.

Due to a recent upward trend in the price of uranium and subsequent increased interest in uranium mining, accurate modeling of baseline dose from environmental sources of radioactivity is of increasing interest. Residual radioactivity model and code (RESRAD) is a program used to model environmental movement and calculate the dose due to the inhalation, ingestion, and exposure to radioactive materials following a placement. This paper presents a novel use of RESRAD for the calculation of dose from non-enhanced, or ancient, naturally occurring radioactive material (NORM). In order to use RESRAD to calculate the total effective dose (TED) due to ancient NORM, a procedural adaptation was developed to negate the effects of time progressive distribution of radioactive materials. A dose due to United States' average concentrations of uranium, actinium, and thorium series radionuclides was then calculated. For adults exposed in a residential setting and assumed to eat significant amounts of food grown in NORM concentrated areas, the annual dose due to national average NORM concentrations was 0.935 mSv y(-1). A set of environmental dose factors were calculated for simple estimation of dose from uranium, thorium, and actinium series radionuclides for various age groups and exposure scenarios as a function of elemental uranium and thorium activity concentrations in groundwater and soil. The values of these factors for uranium were lowest for an adult exposed in an industrial setting: 0.00476 microSv kg Bq(-1) y(-1) for soil and 0.00596 microSv m(3) Bq(-1) y(-1) for water (assuming a 1:1 234U:238U activity ratio in water). The uranium factors were highest for infants exposed in a residential setting and assumed to ingest food grown onsite: 34.8 microSv kg Bq(-1) y(-1) in soil and 13.0 microSv m(3) Bq(-1) y(-1) in water.

Cerebral glucose transport implies individualized glial cell function.

Previous positron emission tomography (PET) measurements of cerebral glucose transport using [11C]-3-O-methylglucose (CMG) suggested an interindividual variation in the values of the rate constant of tracer outflow (k2) larger than that for the clearance rate of inflow (K1). These two parameters were examined in healthy cerebral cortex by dynamic PET in 4 men and 2 women (aged 24 to 73 years) without neurologic disease, and in 1 man (42 years) with a recent left hemispheric cerebral infarction under normoglycemia (average blood plasma d-glucose concentration, 5.44 +/- 1.94 micromol/mL) and again under hyperglycemia (average, 10.24 +/- 1.44 micromol/mL). Time-radioactivity curves were obtained from healthy cortex (grey matter) and plasma and analyzed for the values of K1 and k2 by two graphical approaches and two fitting procedures. Both K1 and k2 significantly declined with increasing plasma glucose levels. A highly significant interindividual but not intraindividual variability for k2 was found at normoglycemia and hyperglycemia. The interindividual variability of K1, although borderline significant, was less than that of k2. Accordingly variable were the distribution volumes K1/k2. These data suggest individualized glial cell function and may be relevant to pathogenesis of neuropsychiatric disease.

Insulin-enhancing vanadium(III) complexes.

Simple, high-yield, large-scale syntheses of the V(III) complexes tris(maltolato)vanadium(III), V(ma)3, tris(ethylmaltolato)vanadium(III), V(ema)3, tris(kojato)vanadium(III) monohydrate, V(koj)3-H2O, and tris(1,2-dimethyl-3-hydroxy-4-pyridinonato)vanadium(III) dodecahydrate, V(dpp)3-12H2O, are described; the characterization of these complexes by various methods and, in the case of V(dpp)3-12H2O, by an X-ray crystal structure determination, is reported. The ability of these complexes to normalize glucose levels in the STZ-diabetic rat model has been examined and compared with that of the benchmark compound BMOV (bis(maltolato)oxovanadium(IV)), an established insulin-enhancing agent.

Vanadyl-biguanide complexes as potential synergistic insulin mimics.

Vanadium has well-documented blood-glucose-lowering properties both in vitro and in vivo. The design of new oxovanadium(IV) coordination compounds, intended for use as insulin-enhancing agents in the treatment of diabetes mellitus, can potentially benefit from a synergistic approach, in which the whole complex has more than an additive effect from its component parts. Biguanides, most importantly metformin, are oral hypoglycemic agents used today to treat type 2 diabetes mellitus. In this study, biguanide, metformin, and phenformin, all biguanides, were coordinated to oxovanadium(IV) to form potential insulin-enhancing compounds. Highly colored, air-stable, bis(biguanidato)oxovanadium(IV), [VO(big)2], bis(N'N'-dimethylbiguanidato)oxovanadium(IV), [VO(metf)2], and bis(beta-phenethyl-biguanidato)oxovanadium(IV), [VO(phenf)2], were prepared. Solvation with dimethylsulfoxide occurred with VO(metf)2 to form a six-coordinate complex. Precursor ligands and oxovanadium(IV) coordination complexes were characterized by infrared spectroscopy, mass spectrometry, elemental analyses, magnetic susceptibility, and, where appropriate, 1H NMR spectroscopy. Biological testing with VO(metf)2, a representative compound, for insulin-enhancing potential included acute (72 h) administration, both by intraperitoneal (i.p.) injection and by oral gavage (p.o.) in streptozotocin (STZ)-diabetic rats. VO(metf)2 administration resulted in significant blood-glucose lowering at doses of 0.12 mmol kg-1 i.p. and 0.60 mmol kg-1 p.o. (previously established as ED50 doses for organically chelated oxovanadium(IV) complexes); however, no positive associative effects due to the presence of biguanide in the complex were apparent.

Vanadium and diabetes.

Vanadium is an ultratrace element, widely distributed in nature, yet with no presently known specific physiological function in mammals. The apparent role of vanadium in regulation of intracellular signaling, as a cofactor of enzymes essential in energy metabolism, and as a possible therapeutic agent in diabetes is of increasing interest as more and more research reports present evidence of vanadium's potentially unique biological function. In this mini-review, the author summarizes current knowledge of the bioinorganic chemistry of vanadium, the basic features of diabetes mellitus and its metabolic sequelae, and the in vitro and in vivo effects of both inorganic and organically-chelated vanadium compounds. Results of clinical trials to date, as well as kinetic studies of tissue uptake are covered. Examples of ways to enhance the positive effects of vanadium as an oral therapeutic adjunct in diabetic control, while minimizing potential toxicity, are compared with regard to desirable features and possible drawbacks.

Molybdenum absorption and utilization in humans from soy and kale intrinsically labeled with stable isotopes of molybdenum.

BACKGROUND: Stable-isotope studies of molybdenum metabolism have been conducted in which molybdenum was added to the diet and was assumed to be absorbed and utilized similarly to the molybdenum in foods. OBJECTIVE: Our objective was to establish whether the molybdenum in foods is metabolized similarly to molybdenum added to the diet. DESIGN: We first studied whether sufficient amounts of molybdenum stable isotopes could be incorporated into wheat, kale, and soy for use in a human study. Enough molybdenum could be incorporated into soy and kale to study molybdenum absorption and excretion. Two studies were then conducted, one in women and one in men. In the first study, each meal contained approximately 100 microg Mo from soy, kale, and extrinsic molybdenum. In the second study, soy and extrinsic molybdenum were compared; the meal contained approximately 300 microg Mo. RESULTS: In the first study, molybdenum was absorbed equally well from kale and an extrinsic source. However, the molybdenum in soy was less well absorbed than the molybdenum in kale or that added to the diet. In the second study, absorption of molybdenum from soy was less than from the extrinsic label. Urinary excretion of soy molybdenum was also lower than urinary excretion of the extrinsic label, but excretion as a percentage of the absorbed dose was not significantly different between treatments. CONCLUSIONS: The molybdenum in soy is less available than molybdenum added to the diet, but the molybdenum in kale is as available as molybdenum added to the diet. Once absorbed, excretion is not significantly different for soy, kale, and extrinsic molybdenum.

Unconjugated estriol as an indication for prenatal diagnosis of steroid sulfatase deficiency by in situ hybridization.

BACKGROUND: Undetectable or very low unconjugated estriol (E3) levels in routine maternal serum screening are associated with steroid sulfatase deficiency, miscarriages, and anencephaly. CASES: Fluorescence in situ hybridization techniques were used in the diagnosis of steroid sulfatase deficiency prenatally in three cases with low or undetectable unconjugated E3 levels. Results showed a male fetus with a deleted steroid sulfatase region, but intact Kallmann syndrome region in all three cases. One mother was studied by fluorescence in situ hybridization and showed a similar deletion for steroid sulfatase gene in one copy of X chromosome (carrier). CONCLUSION: Women with undetectable or very low levels of estriol on serum screening should be counseled regarding steroid sulfatase deficiency with evaluation by fluorescence in situ hybridization.

Kinetic analysis and comparison of uptake, distribution, and excretion of 48V-labeled compounds in rats.

Vanadium has been found to be orally active in lowering plasma glucose levels; thus it provides a potential treatment for diabetes mellitus. Bis(maltolato)oxovanadium(IV) (BMOV) is a well-characterized organovanadium compound that has been shown in preliminary studies to have a potentially useful absorption profile. Tissue distributions of BMOV compared with those of vanadyl sulfate (VS) were studied in Wistar rats by using 48V as a tracer. In this study, the compounds were administered in carrier-added forms by either oral gavage or intraperitoneal injection. Data analyzed by a compartmental model, by using simulation, analysis, and modeling (i.e., SAAM II) software, showed a pattern of increased tissue uptake with use of 48V-BMOV compared with 48VS. The highest 48V concentrations at 24 h after gavage were in bone, followed by kidney and liver. Most ingested 48V was eliminated unabsorbed by fecal excretion. On average, 48V concentrations in bone, kidney, and liver 24 h after oral administration of 48V-BMOV were two to three times higher than those of 48VS, which is consistent with the increased glucose-lowering potency of BMOV in acute glucose lowering compared with VS.

Molybdenum metabolism in men with increasing molybdenum intakes: changes in kinetic parameters.

Molybdenum metabolism was studied in four young men to determine the effect of the amount of dietary molybdenum on molybdenum kinetics. A compartmental model, developed by using data from a study with low dietary molybdenum, was adapted to accommodate five levels of molybdenum. Each level, ranging from 22 to 1,470 micrograms molybdenum/day, was fed for 24 days. Kinetics of absorption and excretion were traced by using 97Mo (intravenous) and 100 Mo (oral) stable-isotope tracers at selected intervals. Urinary and fecal isotope excretion data for 6-day pooled collections were fit to a kinetic model by using SAAM/CONSAM software. Residence times for molybdenum were estimated at 2.4 days in the gastrointestinal tract, 40 min in plasma, from 3.3 to 0.3 days in fast-turnover tissue, and from 63 to 237 days in slow-turnover tissue. As dietary molybdenum increased, residence time decreased in fast-turnover tissue and increased in slow-turnover tissue. The model closely approximated the highly efficient homeostatic mechanisms of molybdenum metabolism over a wide range of intakes.

Kinetic model of molybdenum metabolism developed from dual stable isotope excretion in men consuming a low molybdenum diet.

The aim of this study was to develop a compartmental model of molybdenum metabolism based on stable isotope excretion patterns. Molybdenum (Mo) is an essential trace element in humans, with an estimated safe and adequate daily dietary intake (ESADDI) of 75-250 micrograms Mo/d. Four adult men were fed low molybdenum diets, 22 micrograms Mo/d for a period of 102 d. 97Mo+ and 100Mo stable isotopes, in intravenous and oral doses, respectively, were administered at selected intervals. The resulting 6-d cumulative urinary and fecal isotope excretion data were used to model molybdenum metabolism using SAAM/CONSAM software. A kinetic model, including gastrointestinal (GI), plasma, slow-turnover tissue and fast-turn-over tissue compartments, accurately simulated the observed pattern of urinary and fecal excretion for both stable isotopes in all four subjects. Residence time for molybdenum in the GI tract was estimated at 1.7 +/- 0.4 d. Predicted residence time for plasma molybdenum was 22 +/- 4 min, whereas slow-turnover tissue (possible hepatic) retention averaged 58 +/- 16 d. The model thus permitted estimation of kinetic parameters for molybdenum metabolism in tissues not readily accessible or measurable in humans.

Vanadium compounds as insulin mimics.

That vanadium compounds act in an insulin-mimetic fashion both in vitro and in vivo has been well established. Both inorganic and organic vanadium compounds have been shown to lower plasma glucose levels, increase peripheral glucose uptake, improve insulin sensitivity, decrease plasma lipid levels, and normalize liver enzyme activities in a variety of animal models of both type I and type II diabetes. Vanadium treatment of diabetic animals does not restore plasma insulin levels but may spare pancreatic insulin. Elucidation of the mechanism(s) of action and potentiation of vanadium's insulin-mimetic effect by appropriate ligand binding would seem to be the highest priorities for future investigation.

Myocardial lipid turnover in dilated cardiomyopathy: a dual in vivo tracer approach.

BACKGROUND: Myocardial lipid metabolism appears abnormal in dilated cardiomyopathy (DCM). A dual-tracer approach with two different fatty acid analogs may allow us to observe such alteration in vivo. 15-(Ortho-123I-phenyl)-pentadecanoic acid (oPPA) and 15-(para-123I-phenyl)-pentadecanoic acid (pPPA) have similar kinetics in circulation, diffusion, and transport. However, pPPA in normal myocardium undergoes beta-oxidation and may also be lost from myocardial cells through back-diffusion; oPPA is hardly catabolized and normally retained mainly in the cytosolic lipid pool. Use of both pPPA and oPPA in the dual-tracer approach focuses observation on the turnover of myocardial lipids (with pPPA) that is scaled against loss of fatty acid through back-diffusion into circulation (with oPPA). METHODS AND RESULTS: Fifteen patients with idiopathic DCM and five control subjects were given oPPA and pPPA sequentially for dynamic planar scintigraphy. Uptake and elimination rates were determined for both substrates from three myocardial regions per individual; the corresponding six elimination rate constants and the three differences between them were analyzed for significant alterations in patients from control values. At least 66% of the patients had a significant alteration in myocardial lipid turnover in three types of patterns: (1) increased beta-oxidation, (2) decreased beta-oxidation, and (3) increased back-diffusion, in part associated with decreased beta-oxidation. Even with the limited number of patients and control subjects, the pattern of abnormality of lipid turnover in DMC appeared to be consistent individually but heterogeneous in the patient group. Moreover, a highly significant increase in beta-oxidation was observed for the posterolateral region of the myocardium compared with the anteroseptal and apical regions in control subjects and patients. CONCLUSION: The dual-tracer approach uncovered in vivo that in at least two thirds of the patients with DCM myocardial lipid turnover was significantly altered compared with control values.

Toxicity studies on one-year treatment of non-diabetic and streptozotocin-diabetic rats with vanadyl sulphate.

Streptozotocin-diabetic and non-diabetic rats were given vanadyl sulphate in drinking water at concentrations of 0.5-1.5 mg/ml for one year. It was found that vanadyl treatment did not produce persistent changes in plasma aspartate aminotransferase, alanine aminotransferase, and urea, specific morphological abnormalities in the brain, thymus, heart, lung, liver, spleen, pancreas, kidney, adrenal, or testis, or abnormal organ weight/body weight ratio for these organs in either non-diabetic or diabetic animals. Treatment significantly reduced the incidence of the occurrence of urinary stones in non-diabetic rats. In diabetic animals vanadyl treatment significantly reduced the mortality rate and prevented the elevation of plasma levels of alanine aminotransferase and urea, the increases in organ size, and the occurrence of megacolon but did not affect the development of renal and testicular tumours. Plasma and tissue concentrations of vanadium were determined and found to have the following order of distribution: bone > kidney > testis > liver > pancreas > plasma > brain. Vanadium was retained in these organs at 16 weeks following vanadyl withdrawal while the plasma levels were beneath detection limits. It is concluded that vanadyl sulphate at antidiabetic doses is not significantly toxic to rats following a one-year administration in drinking water, but vanadium may be retained in various organs for months after cessation of treatment.

One-year treatment of streptozotocin-induced diabetic rats with vanadyl sulphate.

Streptozotocin-diabetic and non-diabetic rats were given various concentrations of vanadyl sulphate in drinking water for one year. It was found that vanadyl sulphate caused significant decreases in body weight gain and plasma insulin level in non-diabetic rats, but did not significantly alter fluid and food intakes or plasma levels of glucose, triglycerides, or cholesterol. In diabetic animals, vanadyl treatment significantly alleviated or prevented the occurrence of hyperglycaemia, hypoinsulinaemia, hyperphagia, polydipsia, hyperlipidaemia, or cataract formation, but the slower body weight gain was not improved. There were gradual decreases in the intake of the compound required to correct hyperglycaemia in the values of ED50 with age of the rats. The beneficial effects of vanadyl treatment persisted 16 weeks following the withdrawal of the compound. It is concluded that vanadyl sulphate is an effective agent for chronic therapy of streptozotocin-induced diabetes in rats, and its prolonged use does not lead to the development of tolerance.

Studies of vanadyl sulfate as a glucose-lowering agent in STZ-diabetic rats.

To study the effect of vanadium (V) intake on blood glucose lowering, tissue V concentrations, glutathione reductase (GR) activity, and plasma trace metal concentrations, streptozotocin(STZ)-diabetic rats were treated with vanadyl sulfate (VS) (0.5-1.2 g/l in the drinking water) for up to 12 weeks. Kidney and plasma V concentrations were positively correlated with V intake. Kidney GR activities were not affected by VS treatment nor were plasma cobalt, molybdenum, manganese or lithium concentrations. Individual V intakes were dependent upon severity of diabetes, with more hyperglycemic rats consuming greater quantities of VS solution. A diminished effect on glucose lowering of VS above 1 g/l was noted.

Effect of vanadyl sulfate feeding on susceptibility to peroxidative change in diabetic rats.

The effects of vanadyl sulfate treatment on susceptibility to oxidative stress were investigated in streptozotocin-diabetic Wistar rats. A 2 x 2 factorial design was employed, with four groups of animals: 1) untreated, non-diabetic; 2) vanadyl-treated, non-diabetic; 3) untreated, diabetic; and 4) vanadyl-treated, diabetic. Vanadyl sulfate was administered as a 1.00 to 1.25 mg/ml solution in drinking water. Cataract development was entirely suppressed in vanadyl-treated compared to untreated, diabetic rats. STZ-induction of diabetes diminished glutathione (GSH) levels in liver homogenates; whereas vanadyl treatment resulted in restored levels of this nonenzymatic antioxidant. Thiobarbituric acid reactive substances (TBARS), both basal and iron-stimulated, were significantly elevated in all vanadyl-treated animals. Vanadyl treatment lowered liver glutamine synthetase activities in diabetic rats, but not in non-diabetic animals. Thus, vanadyl treatment was antioxidant in terms of cataract formation and reduced glutathione concentration in liver homogenates, pro-oxidant by reason of iron-stimulated TBARS formation and inconclusive with respect to glutamine synthetase activity. These results highlight the importance of using multiple indicators of peroxidative change in evaluating new pro-oxidant/antioxidant treatment regimens.