A review of the behaviour of U-238 series radionuclides in soils and plants.

The U-238 series of radionuclides is of relevance in a variety of environmental contexts ranging from the remediation of former uranium mining and milling facilities to the deep geological disposal of solid radioactive wastes. Herein, we review what is known concerning the behaviour of radionuclides from the U-238 decay chain in soils and plants. This review is intended to provide a single comprehensive source of information to anyone involved in undertaking environmental impact assessment studies relating to this decay chain. Conclusions are drawn relating to values and ranges of distribution coefficients appropriate to uranium, thorium, radium, lead and polonium in different soil types and under various environmental conditions. Similarly, conclusions are drawn relating to plant:soil concentration ratios for these elements for different plant and soil types, and consideration is given to the distribution of these elements within plants following both root uptake and foliar application.

Short TE (7) Li-MRS confirms Bi-exponential lithium T2 relaxation in humans and clearly delineates two patient subtypes.

PURPOSE: (i) To develop an MRS technique to measure (7) Li levels in human brain in a reasonable scan time, (ii) to develop a technique to quantify (7) Li T2 relaxation times as measured from human brain in patients taking lithium for the treatment of their bipolar disorder, and (iii) to confirm or refute the presence of bi-exponential (7) Li T2 relaxation in human brain. MATERIALS AND METHODS: We modified a spin-echo MRS pulse sequence to decrease its minimum echo time. With IRB approval, we performed lithium MRS with the modified pulse sequence on 13 euthymic bipolar patients stable on long-term lithium to treat their disease. RESULTS: We were able to achieve a total scan time per sample of 8:20; total scan time including imaging, calibration and MRS was approximately 1 h 15 min. We observed bi-exponential T2 relaxation in the majority of patients, with an average short decay time of 5.3 ± 1.4 ms and an average long decay time of 68.2 ± 10.2 ms. However, in two patients we observed strongly mono-exponential T2 relaxation with an average decay time of 47.4 ± 1.3 ms. CONCLUSION: (7) Li relaxation patterns may prove useful to distinguish between lithium-responsive and lithium nonresponsive bipolar patients.

Yokukansan inhibits morphine tolerance and physical dependence in mice: the role of α2A-adrenoceptor.

Yokukansan (YKS) is a traditional Japanese medicine consisting of seven medicinal herbs that is used for the treatment of neurosis, insomnia, and the behavioral/psychological symptoms of dementia. This study examined the effects of YKS on morphine tolerance and physical dependence in mice. Daily oral administration of YKS (0.5 or 1.0 g/kg) for 3 weeks significantly attenuated morphine tolerance and naloxone-precipitated morphine withdrawal signs (jumps and body weight loss) without affecting the analgesic effect of morphine. The inhibitory effect of YKS on withdrawal jumps in morphine-dependent mice was blocked by a single pretreatment with an α(2)-adrenoceptor antagonist, yohimbine, but not by an α(1)-adrenoceptor antagonist, prazosin. A similar inhibitory effect on withdrawal jumps was observed by repeated administration of yohimbine. The membrane expression of α(2A)-adrenoceptors in the pons/medulla was decreased in morphine withdrawn animals; this reduction was prevented by repeated administration of YKS or yohimbine. Competitive radioligand and [(35)S]guanosine-5'-O-(3-thiotriphosphate) binding assays revealed that YKS and its constituent herbs, Glycyrrhiza (GR) and Uncaria hook (UH), had specific binding affinity for and antagonist activity against the α(2A)-adrenoceptor. Certain chemical constituents, including GR -derived glycyrrhizin and its metabolite, 18ß-glycyrrhetinic acid, and UH-derived geissoschizine methyl ether (GME), shared such activities. Repeated administration of GR, UH, glycyrrhizin or GME significantly inhibited morphine withdrawal signs. These results suggest that YKS and its active constituents inhibit morphine tolerance and physical dependence, and that the latter is due at least in part to the prevention of the decreased membrane expression of the α(2A)-adrenoceptor in the brainstem by its prolonged blockade.

Human urinary excretion and metabolism of (82)Se-enriched selenite and selenate determined by LC-ICP-MS.

Urinary excretion of selenium after ingestion of isotope labeled selenite and selenate was studied in seven healthy volunteers, 4 men and 3 women (age 28-50 years). An aqueous solution containing 330 µL (82)Se-selenate (corresponding to 74.3 µg (82)Se) was given orally and urine samples were subsequently collected during the following 24 hours. The scheme was repeated four weeks later with a 280 µL (82)Se-selenite solution (corresponding to 74.4 µg (82)Se). The amount of total Se in the urine samples was determined by inductively coupled mass spectrometry. The mean total urinary excretion of (82)Se following (82)Se-selenate administration was 33.7% (range 15.6-42.5%) while the mean total excretion of (82)Se after (82)Se-selenite administration was 3.2% (range 2.8-3.9%) of the ingested amount. LC-ICPMS analysis of the urine samples showed that the majority of the selenium excreted after selenate ingestion was unchanged selenate for 6 of the individuals while one individual had metabolized a fraction (approx. 20%) of the selenate to selenosugar. Ingestion of 10 times larger doses of selenite in two individuals resulted in 13-23% excretion primarily excreted as selenosugar. These results show that the human metabolic pathways of selenite and selenate are different and indicate that not all selenate, although well absorbed, may be available for the beneficial health effects.

Essential role for orbitofrontal serotonin 1B receptors in obsessive-compulsive disorder-like behavior and serotonin reuptake inhibitor response in mice.

BACKGROUND: Perseveration and sensorimotor gating deficits are core features of obsessive-compulsive disorder (OCD). Serotonin 1B receptor (5-HT1BR) agonists exacerbate OCD symptoms in patients and induce perseveration and sensorimotor gating deficits in mice. Serotonin reuptake inhibitors (SRIs), but not noradrenaline reuptake inhibitors (NRIs), reduce OCD symptoms following 4 to 8 weeks of treatment. Using mice, we compared the effects of chronic SRI versus NRI treatment on 5-HT1BR-induced OCD-like behavior and 5-HT1BR sensitivity in orbitofrontal-subcortical OCD circuits. Furthermore, we localized the 5-HT1BR population that mediates OCD-like behavior. METHODS: Mice chronically received the SRI clomipramine or the NRI desipramine and were examined for 5-HT1BR-induced OCD-like behavior or 5-HT1BR binding and G-protein coupling in caudate putamen, nucleus accumbens, and orbitofrontal cortex. Separate mice were tested for OCD- or depression-like behavior following 4, 14, 21, 28, or 56 days of SRI treatment. Finally, OCD-like behavior was assessed following intra-orbitofrontal 5-HT1BR agonist infusion or intra-orbitofrontal 5-HT1BR antagonist infusion coupled with systemic 5-HT1BR agonist treatment. RESULTS: Effective, but not ineffective, OCD treatments reduced OCD-like behavior in mice with a time course that parallels the delayed therapeutic onset in OCD patients and downregulated 5-HT1BR expression in the orbitofrontal cortex. Intra-orbitofrontal 5-HT1BR agonist infusion induced OCD-like behavior, and intra-orbitofrontal 5-HT1BR antagonist infusion blocked OCD-like effects of systemic 5-HT1BR agonist treatment. CONCLUSIONS: These results indicate that orbitofrontal 5-HT1BRs are necessary and sufficient to induce OCD-like behavior in mice and that SRI pharmacotherapy reduces OCD-like behavior by desensitizing orbitofrontal 5-HT1BRs. Our findings suggest an essential role for orbitofrontal 5-HT1BRs in OCD pathophysiology and treatment.

Boron biodistribution study in colorectal liver metastases patients in Argentina.

Ex-situ BNCT for multifocal unresectable liver metastases employing whole or partial autograft techniques requires knowledge of boron concentrations in healthy liver and metastases following perfusion and immersion in Wisconsin solution (W), the procedure employed for organ preservation during ex-situ irradiation. Measurements of boron concentration in blood, liver and metastases following an intravenous infusion of BPA-F in five colorectal liver metastases patients scheduled for surgery were performed. Tissue samples were evaluated for boron content pre and post perfusion and immersion in W. Complementary histological studies were performed. The data showed a dose-dependent BPA uptake in liver, a boron concentration ratio liver/blood close to 1 and a wide spread in the metastases/liver concentration ratios in the range 0.8-3.6, partially attributable to histological variations between samples. Based on the boron concentrations and dose considerations (liver < or =15 Gy-Eq and tumor> or =40 Gy-Eq) at the RA-3 thermal neutron facility (mean flux of about (6+/-1) x 10(9) n cm(-2)s(-1)), ex-situ treatment of liver metastases at RA-3 would be feasible.

Boron neutron capture therapy (BNCT) for the treatment of spontaneous nasal planum squamous cell carcinoma in felines.

Recently, Boron neutron capture therapy (BNCT) was successfully applied to treat experimental squamous cell carcinomas (SCC) of the hamster cheek pouch mucosa, with no damage to normal tissue. It was also shown that treating spontaneous nasal planum SCC in terminal feline patients with low dose BNCT is safe and feasible. In an extension of this work, the present study aimed at evaluation of the response of tumor and dose-limiting normal tissues to potentially therapeutic BNCT doses. Biodistribution studies with (10)B-boronophenylalanine (BPA enriched in (10)B) as a (10)B carrier were performed on three felines that showed advanced nasal planum SCC without any standard therapeutic option. Following the biodistribution studies, BNCT mediated by (10)BPA was done using the thermalized epithermal neutron beam at the RA-6 Nuclear Reactor. Follow-up included clinical evaluation, assessment of macroscopic tumor and normal tissue response and biopsies for histopathological analysis. The treated animals did not show any apparent radiation-induced toxicity. All three animals exhibited partial tumor control and an improvement in clinical condition. Enhanced therapeutic efficacy was associated with a high (10)B content of the tumor and a small tumor size. BNCT is therefore believed to be potentially effective in the treatment of spontaneous SCC. However, improvement in targeting (10)B into all tumor cells and delivering a sufficient dose at a greater depth are still required for the treatment of deep-seated, large tumors. Future studies are needed to evaluate the potential efficacy of the dual mode cellular (e.g. BPA-BNCT) and vascular (e.g. GB-10-BNCT) targeting protocol in a preclinical scenario, employing combinations of (10)B compounds with different properties and complementary uptake mechanisms.

Characterizing dissolved Cu and Cd uptake in terms of the biotic ligand and biodynamics using enriched stable isotopes.

The biotic ligand model considers the biological and geochemical complexities that affect metal exposure. It relates toxicity to the fraction of physiological active sites impacted by reactive metal species. The biodynamic model is a complementary construct that predicts bioaccumulation and assumes that toxicity occurs when influx rates exceed rates of loss and detoxification. In this paper we presume that metal influx rates are mechanistically the resulting processes that characterize transmembrane transport. We use enriched stable isotopes to characterize, both in terms of the biotic ligand and biodynamics, dissolved metal uptake by a freshwater snail at water hardness varying up to 180-fold. Upon 24 h exposure, metal uptake was linear over a range encompassing most environmental concentrations; although saturation kinetics were observed at higher concentrations. Cadmium influx rates correlate with changes in the affinity of the biotic ligand, whereas those of Cu correlate with changes in both site affinity and capacity. A relationship between metal influx rate and ligand character asks whether toxicity is the result of accumulation at the biotic ligand or the rate at which metal is transported by that ligand.

Effects of Vitamin E on airway responses and biochemical parameters in guinea pigs sensitized to ovalbumin.

The effect of dietary supplementation with Vitamin E was studied in sensitized guinea pigs. After measurement of baseline airway reactivity and sensitization with ovalbumin, the animals were randomized into two groups: Group A, on a commercial feed and Group B, on dietary supplementation with oral Vitamin E (0.7 IU/kg). These were challenged with inhaled ovalbumin after 4 weeks. The following outcomes were studied: airway responses to ovalbumin inhalation, airway reactivity, sodium and calcium ion influx in isolated tracheal cells, Na+ K+ ATPase and Ca2+ ATPase activity in tracheal homogenate and plasma malonaldehyde. Sensitization increased airway reactivity in Group A but not in Group B. The tracheal cells of animals in Group B showed significantly lower rates of 45Ca and 22Na influx and lower activities of tracheal Na+ K+ ATPase and Ca2+ ATPase as compared to Group A. Plasma malonaldehyde was similar between two groups. We concluded that Vitamin E suppresses the increase in airway reactivity following sensitization and has membrane stabilizing actions.

Biodistribution of 10B in a rat liver tumor model following intra-arterial administration of sodium borocaptate (BSH)/degradable starch microspheres (DSM) emulsion.

We reported that intra-arterial administration of borocaptate sodium (BSH)/lipiodol emulsion provided selectively high (10)B concentrations (approximately 200 ppm 6 h after administration) in experimental liver tumors. In the present study, we investigated the pharmacokinetics of BSH following intra-arterial administration of BSH with other embolizing agent, degradable starch microspheres (DSM). The (10)B concentration in the tumor at 1 h after administration of BSH with DSM was 231 ppm. At 6 h, the (10)B concentration in the tumor in BSH with DSM group was 81.5 ppm. The (10)B concentration in the liver at 1 h after administration of BSH with DSM was 184 ppm. At 6 h, the(10)B concentration in the liver in BSH with DSM group was 78 ppm. The tumor/liver (10)B concentration ratios (T/L ratio) in the "BSH+DSM" group were significantly smaller than those in the "BSH+lipiodol" group at 1 h (1.4 vs. 3.6) and 6h (1.1 vs. 14.9). BSH/DSM-boron neutron capture therapy (BNCT) was not suitable for treatment of multiple liver tumors due to the low T/L (10)B concentration ratio. However, the high (10)B accumulation in the liver tumors following intra-arterial administration of BSH/DSM emulsion suggests that BSH/DSM-BNCT has the potential for application to malignant tumors in other sites.

Differential involvement of 5-HT(1B/1D) and 5-HT6 receptors in cognitive and non-cognitive symptoms in Alzheimer's disease.

Growing evidence suggests that a compromised serotonergic system plays an important role in the pathophysiology of Alzheimer's disease (AD). We assessed the expression of 5-HT(1B/1D) and 5-HT(6) receptors and cholinacetyltransferase (ChAT) activity in post-mortem frontal and temporal cortex from AD patients who had been prospectively assessed for cognitive function using the Mini-Mental State Examination (MMSE) and behavioral changes using the Present Behavioral Examination (PBE). 5-HT(1B/1D) and 5-HT(6) receptor densities were significantly reduced in both cortical areas. 5-HT(1B/1D) receptor density was correlated to MMSE decline in the frontal cortex, supporting its implication in memory impairment. The best predictor for lowered 5-HT(6) receptor density in the temporal cortex was the PBE measure of overactivity. The 5-HT(6)/ChAT ratio was related to aggression both in the frontal and temporal cortex. Therefore, antagonists acting at 5-HT(6) receptors could be useful in the treatment of non-cognitive symptoms associated to AD.

Effects of sulphate- and bicarbonate-rich mineral waters on net and fractional intestinal absorption and urinary excretion of magnesium in rats.

Magnesium (Mg) intake is below the recommended daily allowances in many developed countries. Mg-rich mineral waters can provide significant amounts of energy-free Mg and thus help to meet Mg requirements. We assessed the effects of different Mg-rich mineral waters on overall intestinal Mg absorption and urinary Mg excretion in 40 rats split into four groups: one received distilled water, another a solution of MgCl(2) and the others two different mineral waters, sulphated water (Hépar) and carbonated water (Badoit) mixed with the diet and as drinking water, for four weeks. The rats were given 3 mg of (26)Mg orally and 0.5 mg of (25)Mg intravenously. They were placed in metabolic cages, and diet consumption, and faeces and urine excretion were monitored during the last four days of the experiment. The rats were then sacrificed and blood was sampled. Mg levels in the diet, faeces, urine and biological samples were measured by atomic absorption spectrometry. Mg stable isotope measurements were performed by ICP/MS. Mg-rich mineral waters significantly increased net intestinal absorption of Mg by more than 30%, but the proportions of both apparent and true intestinal absorption of Mg were similar in all four groups. Thus, net and fractional retention of Mg were similar in the three Mg-supplemented groups. In conclusion, both types of Mg-rich mineral waters studied similarly increased both absorption and urinary excretion of Mg with no positive effect on the overall retention of Mg, probably because the Mg status of the rats was already satisfactory.

Using stable isotopes to assess the bioavailability of minerals in food-fortification programs.

Food fortification with minerals is often undertaken without consideration of the bioavailability or nutrient-nutrient interactions related to its use. Stable isotopes provide a safe and accessible approach to providing direct evidence regarding these issues. Studies can be applied in all areas of the world and in all population groups. Mineral stable isotopes are safe and meet stringent ethical standards for use in children. Clinical studies in children allowing scientists, policy makers and the food industry to obtain data needed to understand how best to fortify foods to enhance the nutritional health of children of all ages. It is not necessary to have analytical mass spectrometry equipment available in each country where studies are performed. Rather, international collaborations can be developed to allow clinical studies to be performed in the field setting with analysis elsewhere if needed. The combination of isotope studies with field intervention trials may be beneficial.