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Dietary boron intakes of selected populations in the United States.

Knowledge of daily boron (B) intakes will assist researchers in establishing B requirements and elucidating the metabolic role of B in humans. B concentrations in commonly consumed foods were utilized to approximate the B intake of selected US populations. Triplicate food samples were digested at low temperatures with 16 M HNO3 and 30% H2O2, and analyzed by inductively coupled plasma spectroscopy (ICP). Milk and dairy products, juices, and beverages were the largest contributors to dietary B. Total B content of average daily diets ranged from 548 microg for toddlers (2 yr old) to 883 microg for mature males (60-65 yr old), excluding tap water contributions. Toddlers consumed 3.7 times more B than mature males when adjusted for body weight (body wt) and consumed the diet with the highest boron density (1.8 microg/kJ or 0.43 microg/kcal). Adolescent females consumed a diet with the lowest B density (1.12 microg/kJ or 0.26 microg/kcal). Food B concentrations applied to diet records (1020 microg/d) and ICP analysis of the corresponding food composites (1170 microg/d) were comparable (p < 0.05). Current estimations of B in US diets are consistent with reports in the literature stating that normal adult daily B intakes are approx 1 mg.

Adolescent↗

The effect of boron supplementation on its urinary excretion and selected cardiovascular risk factors in healthy male subjects.

Boron (B) is an essential trace element for plants and its interrelationship with mineral and bone metabolism and endocrine function in humans has been proposed. Relatively little is known about the occurrence of B in the food chain and hence a biomarker which reflects its intake is required. Two studies were carried out to quantify the urinary B concentration of subjects consuming their habitual diet and the effect of supplementation. In addition, the effect of supplementation on plasma lipoprotein cholesterol concentrations and susceptibility to oxidation and plasma steroid hormones were determined. Boron excretion, obtained on two different occasions from 18 healthy male subjects, was found to be in the range 0.35-3.53 mg/day, with no significant difference between the two occasions. Supplementation with 10 mg B/d for 4 wk resulted in 84% of the supplemented dose being recovered in the urine. Plasma estradiol concentrations increased significantly as a result of supplementation (51.9 +/- 21.4 to 73.9 +/- 22.2 pmol/L; p < 0.004) and there was a trend for plasma testosterone levels to be increased. However, there was no difference in plasma lipids or the oxidizability of low-density lipoprotein. Our studies suggest that the absorption efficiency of B is very high and estimation of the urinary B concentration may provide a useful reflection of B intake. In addition, the elevation of endogenous estrogen as a result of supplementation suggests a protective role for B in atherosclerosis.

Adolescent↗

Concentration of LAS and boron in the Itter. Comparison of measured data with results obtained by simulation with the GREAT-ER software.

The GREAT-ER software was used to calculate linear alkylbenzene sulphonate [LAS] and boron concentrations in the Itter stream in North Rhine-Westfalia, Germany. The aim was to investigate the predictive strength of this newly developed tool and to compare its results to measured data. Substance-specific input data which were used in this scenario were partly generic (e.g. LAS and sodium perborate tetrahydrate consumption figures for Germany) and partly (site-)specific data (e.g. half-life time for LAS elimination). The comparison with the measured data reveals that the model predictions for LAS and boron are correct at least within a factor of two, only if generic German consumption data is applied. By using refined input data, the accuracy can be increased further.

Alkanesulfonic Acids↗

Comparison of radiation effects of gadolinium and boron neutron capture reactions.

PURPOSE: Cell survival assays were performed to evaluate the effects of radiations released during neutron capture reactions by gadolinium-157, boron-10 and by the combination of both. MATERIALS AND METHODS: Single cell suspensions with or without Gd-157 and/or B-10 were exposed to thermal neutrons produced by the Kyoto University reactor, and standard cell survival curves were obtained. RESULTS: Under the same molarity, cytocidal effects were 1.5 times greater for Gd-157 than for boron when compared at 10% survival levels. The presence of B-10 enhanced the radiation effect of Gd-157 neutron capture by 1.2-fold, suggesting that cells were not sufficiently irradiated as a result of neutron fluency attenuation by the presence of excess neutron capture agents in the medium. CONCLUSIONS: When an equal number of atoms were present, Gd-157 was effective as B-10 when exposed to an equal number of thermal neutrons. However, there was no benefit observed in the combination of Gd-157 and B-10 for neutron capture therapy. Further studies are needed to determine optimal Gd-157 and B-10 concentrations as a function of tumor dimension.

Animals↗

Mercury-free sono-electroanalytical detection of lead in human blood by use of bismuth-film-modified boron-doped diamond electrodes.

We report the electroanalytical determination of lead by anodic stripping voltammetry at in-situ-formed, bismuth-film-modified, boron-doped diamond electrodes. Detection limits in 0.1 mol L(-1) nitric acid solution of 9.6 x 10(-8) mol L(-1) (0.2 ppb) and 1.1 x 10(-8) mol L(-1) (2.3 ppb) were obtained after 60 and 300 s deposition times, respectively. An acoustically assisted deposition procedure was also investigated and found to result in improved limits of detection of 2.6 x 10(-8) mol L(-1) (5.4 ppb) and 8.5 x 10(-10) mol L(-1) (0.18 ppb) for 60 and 300 s accumulation times, respectively. Furthermore, the sensitivity obtained under quiescent and insonated conditions increased from 5.5 (quiescent) to 76.7 A mol(-1) L (insonated) for 60 s accumulation and from 25.8 (quiescent) to 317.6 A mol(-1) L (insonated) for 300 s accumulation. Investigation of the use of ultrasound with diluted blood revealed detection limits of the order of 10(-8) mol L(-1) were achievable with excellent inter- and intra-reproducibility and sensitivity of 411.9 A mol(-1) L. For the first time, electroanalytical detection of lead in diluted blood is shown to be possible by use of insonated in-situ-formed bismuth-film-modified boron-doped diamond electrodes. This method is a rapid, sensitive, and non-toxic means of clinical sensing of lead in whole human blood.

Bismuth↗

Boron uptake by ectomycorrhizas of silver birch.

Boron (B) is an essential micronutrient for plants but it is thought not to be essential for fungi. We studied whether the extraradical mycelia of Paxillus involutus in symbiosis with silver birch (Betula pendula) take up B and transport it to the host plant. We grew mycorrhizal plants in flat microcosms with a partitioning wall, below which there was only extraradical mycelium. A boric acid solution enriched in 10B was applied to these mycelia. Increased 10B/11B isotope ratios were subsequently measured in birch leaves, stems, and roots plus mycorrhizas in the upper compartment. Boron was therefore taken up by the mycorrhizal mycelia and transported to the host plant in this species combination.

Basidiomycota↗

Betaine:homocysteine methyltransferase from rat liver: purification and inhibition by a boronic acid substrate analog.

Betaine:homocysteine methyltransferase (BHMT) from rat liver has been highly purified by an efficient procedure requiring only two chromatographic steps: Sephadex G-100 chromatography and fast protein liquid chromatography chromatofocusing. A 170-fold purification and 7.5% overall yield were achieved. Chromatofocusing yielded three active forms of BHMT with pI values near 8.0, 7.6, and 7.0. The subunit molecular weight of each active form is 45,000 Da as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the native enzyme has a molecular weight of 270,000 as determined by exclusion chromatography. The stability of the purified enzyme was found to be potentiated by the presence of 1 mM dimethylglycine and 1 mM homocysteine. Boronate analogs of betaine (pinanyl N,N,N-trimethylaminomethaneboronate) (4) and dimethylglycine (pinanyl N,N-dimethylaminomethaneboronate) were synthesized from pinanyl iodomethaneboronate (3) and trimethylamine or dimethylamine, respectively. The free acid of the betaine analog (5) was reversibly generated from (4). The inhibition of BHMT by (5) appears competitive with a Ki = 45 microM. Since the Km for betaine measured with the purified enzyme is near 0.1 mM, the boronic acid analog of betaine appears to function effectively as a substrate analog inhibitor of BHMT. The analog does not appear to act as a methyl donor to homocysteine when (5) is substituted for betaine in the enzyme reaction. In addition, an enzyme assay based upon C3-cyano reverse phase HPLC detection of the o-phthalaldehyde derivative of methionine was developed as an alternative to the standard radiochemical assay. Betaine:homocysteine methyltransferase in the picomole range can be quantitated using this assay as indicated by a linear response of enzyme activity to protein concentration.

Animals↗

Increase in blood plasma levels of boron and strontium in hemodialyzed patients.

Boron and strontium concentrations in blood plasma of controls and hemodialyzed patients from two Centers were determined by inductively coupled plasma emission spectrometry. Boron concentrations in blood plasma were respectively, in controls 2.6 +/- 0.9 mumol/l and in hemodialyzed patients 16.1 +/- 5.6 mumol/l before the dialysis session and 9.5 +/- 3.2 mumol/l at the end. The decrease in blood plasma during the dialysis was concomitant with an increase in the dialysis fluid (1.2 +/- 0.7 mumol/l at the beginning and 4.6 +/- 1.8 mumol/l at the end). Strontium concentrations in blood plasma were respectively, in controls 0.22 +/- 0.06 mumol/l and in hemodialyzed patients 0.62 +/- 0.24 mumol/l before the dialysis session and 0.64 +/- 0.14 mumol/l at the end. The mean concentration of strontium in the dialysis fluid was the same before (0.49 +/- 0.11 mumol/l) and after the dialysis session (0.49 +/- 0.10 mumol/l), but a transfer between plasma and dialysis fluid was shown by individual changes. Some considerations about these results are put forward but their possible clinical consequences are not yet known.

Adult↗

Better histology and biochemistry for osteoblasts cultured on titanium-doped bioactive glass: bioglass 45S5 compared with iron-, titanium-, fluorine- and boron-containing bioactive glasses.

In the present study we used an established cell culture model to compare Bioglass 45S5 with four other bioactive glasses. Small substitutions or additions of certain ions like iron, titanium, fluorine or boron modified the basic 45S5 glass network. We used several histological and biochemical parameters to interpret the results found in terms of the used model. Regarding 45S5 as a reference, we found that osteoblasts cultured on iron-doped bioactive glass showed a more flattened morphology, and both lower proliferation rate and osteoblast expression. Osteoblasts cultured on titanium-doped glasses also showed a flattened morphology, but higher proliferation and remarkably higher osteoblast expression. On fluorine- and boron-containing glasses the osteoblasts showed a rather compact morphology, a normal proliferation but only moderate osteoblast expression. With microprobe analysis it was shown that the formation of calcium and phosphorus on titanium-doped glass was relatively lower and the release of sodium slower when compared with 45S5. Osteoblasts cultured on titanium-doped bioactive glasses demonstrated superior histological and biochemical parameters when compared with the other glass types. Further research into the physico-chemical properties and the in vivo behaviour of doped bioactive glasses is recommended.

Alkaline Phosphatase↗

N-(5-dimethylaminonaphthalene-1-sulfonyl)-3-aminobenzene boronic acid as an active-site-directed fluorescent probe of lipoprotein lipase.

Resonance energy transfer was used to monitor the interaction of an active-site-directed fluorescent inhibitor, N-(5-dimethylaminonaphthalene-1-sulfonyl)-3-aminobenzene boronic acid, and lipoprotein lipase (EC 3.1.1.34). The binding of this probe to the active site of lipoprotein lipase had an association constant, Ka, of 1.1 X 10(6) M-1, indicating a strong interaction. The binding was displaced competitively by benzene boronic acid. The method described provides a sensitive procedure to probe the active site of lipoprotein lipase.

Animals↗

Serum cholinesterase inhibition by boronic acids.

Horse serum cholinesterase (acylcholine acylhydrolase, EC 3.1.1.8) was reversibly inhibited by a variety of alkyl- and areneboronic acids with Ki values ranging from 6.2 mM (methaneboronic acid) to 3.1 microM (diphenylboric acid). Binding to the enzyme was apparently at the active center, because inhibition obeyed competitive kinetics and because boronic acids protected the enzyme from inactivation by phenylmethanesulfonyl fluoride. Boronic acids should prove useful in probing the active center of serum cholinesterase.

Animals↗

NMR studies of the alpha-chymotrypsin-(R)-1-acetamido-2-(4-fluorophenyl)ethane-1-boronic acid complex at pH 7.

The interaction of (R)-1-acetamido-2-(4-fluorophenyl)ethane-1-boronic acid with alpha-chymotrypsin at pH 7 was studied by a variety of fluorine and proton NMR experiments and the results compared to observations made at pH 4. It was demonstrated that this compound forms a complex with a 1:1 stoichiometry at pH 7; proton NMR indicates that the boronic acid likely is coordinated to the serine-195 residue at the active site. Analysis of fluorine T1 relaxation behavior and 19F(1H) NOE data shows that the rate constant for dissociation of the complex is 4.7 s-1, somewhat faster than is observed at pH 4. The data analysis and the results of two-dimensional 19F(1H) NOE experiments show that interactions between the fluoroaromatic ring of the inhibitor and the enzyme are weaker at the higher pH value, although the motion of the fluoroaromatic ring within the complex appears to be just as restricted as is the case at pH 4.

Boronic Acids↗

Boron neutron capture irradiation of the rat spinal cord: effects of variable doses of borocaptate sodium.

The Fischer 344 rat spinal cord model has been used to evaluate the response of the central nervous system to boron neutron capture irradiation with variable doses of the neutron capture agent, borocaptate sodium (BSH). Three doses of BSH, 190, 140 and 80 mg/kg body weight, administered by i.p. injection, were used to establish the time course of 10B accumulation in and removal from the blood. After administration of the two lower doses of BSH, blood 10B levels peaked at 0.5 h after injection, with no significant (P > 0.1) change at 1 h after injection. Beyond this time point, levels of 10B in the blood began to decrease after a dose of 80 mg/kg BSH, but remained constant until 3 h after administration after the two higher doses of BSH. Myelopathy developed after latent intervals of 20.4 +/- 0.1, 20.8 +/- 1.4, 15.0 +/- 0.8, 15.4 +/- 0.4 and 15.6 +/- 0.4 weeks, following irradiation with thermal neutrons in combination with BSH at doses of 20, 40, 80, 140 and 190 mg/kg body weight, respectively. The radiation-induced lesion in the spinal cord was white matter necrosis. ED50 values for myelopathy were calculated from probit-fitted dose-effect curves. Expressed as total physical absorbed doses, these values were 20.7 +/- 1.9, 24.9 +/- 1.2, 27.2 +/- 0.9, 28.4 +/- 0.6 and 32.4 +/- 1.9 Gy after irradiation with thermal neutrons in the presence of 20, 40, 80, 140 and 190 mg/kg body weight of BSH, respectively. The compound biological effectiveness (CBE) factor values, estimated from this data, were in the range 0.49-0.55. There was no significant (P > 0.1) variation in the CBE factor for BSH as a function of increasing 10B concentration in the blood. It was concluded that there was no significant synergistic interaction between the low and high linear energy transfer (LET) components of the boron neutron capture (BNC) radiation field.

Animals↗

Clinical results of long-surviving brain tumor patients who underwent boron neutron capture therapy.

PURPOSE: The present report is a review of long-term survivors in the patients with malignant brain tumors treated by boron neutron capture therapy. METHODS AND MATERIAL: One-hundred twenty patients with 119 intracranial tumors and one extracranial nerve-related tumor were treated by the current standard technique of boron-neutron capture therapy (BNCT) as of December 1992, using 10B-sodium-mercaptoundecahydrododecaborate. RESULTS: Out of 87 patients operated on before May 1987, 18 lived or have lived longer than 5 years. Nine of these 18 lived or have lived longer than 10 years out of 53 patients operated on before May 1982. Among more-than-10-year survivors, only two died at 17 and 12 years. All of the other are still alive. The two died of delayed radiation damage because BNCT was applied to glioblastomas which recurred after their conventional radiotherapy. They lacked evidence of tumors when they died. Out of these nine more-than-10-year survivors, three had been previously treated by conventional external radiotherapy and they developed radiation damage which brought all patients ultimately to an incapacitated condition. Two of the three died. All the other 6 who were free from previous radiation history are active in their jobs and have no evidence of tumors. CONCLUSION: It can be suggested that BNCT is a radiotherapy that can produce "cure" of both malignant and benign brain tumors while preserving a good quality of life if conducted without conventional radiotherapy.

Adult↗

Boron neutron capture therapy: a mechanism for achieving a concomitant tumor boost in fast neutron radiotherapy.

PURPOSE: For many years neutron radiation has been used to treat malignant disease both as fast neutron radiotherapy and as thermal neutron induced boron neutron capture therapy (BNCT). To date, these two approaches have been used independently of one another due to the large difference in neutron energies each employs. In this paper we discuss the potential application of BNCT to enhance the therapeutic effectiveness of a fast neutron radiotherapy beam. METHODS AND MATERIALS: Measurements are presented for the thermal neutron component that is spontaneously developed as the University of Washington fast neutron radiotherapy beam penetrates a water phantom. The biological effect of this thermalized component on cells "tagged" with boron-10 (10B) is modeled mathematically and the expected change in cell survival calculated. The model is then extended to estimate the effect this enhanced cell killing would have for increased tumor control. RESULTS: The basic predictions of the model on changes in cell survival are verified with in vitro measurements using the V-79 cell line. An additional factor of 10-100 in tumor cell killing appears achievable with currently available 10B carriers using our present neutron beam. A Poisson model is then used to estimate the change in tumor control this enhanced cell killing would produce in various clinical situations and the effect is sufficiently large so as to be clinically relevant. It is also demonstrated that the magnitude of the thermalized component can be increased by a factor of 2-3 with relatively simple changes in the beam generating conditions. CONCLUSION: BNCT may provide a means of enhancing the therapeutic effectiveness of fast neutron radiotherapy in a wide variety of clinical situations and is an area of research that should be aggressively pursued.

Boron Neutron Capture Therapy↗

Determination of vanilmandelic acid in urine by coupled-column liquid chromatography combining affinity to boronate and separation by anion exchange.

An automated liquid chromatographic method for assaying vanilmandelic acid in urine is described. Vanilmandelic acid and potential interfering substances, such as catechol compounds and their metabolites, have been tested for affinity to boronic acid-substituted silica at various pH values. Vanilmandelic acid and the internal standard, isovanilmandelic acid, were bound to the boronate matrix at an acidic pH, whereas for instance catecholamines were unretained and passed through the column. The alpha-hydroxycarboxylic acids were then desorbed by another mobile phase (pH 6.0) and transferred to an anion exchanger for chromatography and electrochemical detection. A relative standard deviation of 2.8% was obtained for the analysis of human urine samples containing 6.6 microM vanilmandelic acid.

Boron Compounds↗

Selective extraction of quercetrin in vegetable drugs and urine by off-line coupling of boronic acid affinity chromatography and high-performance liquid chromatography.

Quercetrin, quercetin and chlorogenic acid were measured in urine or in drugs by combination of boronic acid affinity chromatography and HPLC. Simple reversed-phase HPLC with UV detection was used to determine quercetrin in five different Solidago virgaurea drugs. For determination of quercetrin in human urine immobilized boronic acid was applied for sample pretreatment. this procedure leads to a determination limit of 0.01 micrograms/ml with a recovery rate of 95.3%. The first results using this method for quercetrin pharmacokinetics are presented.

Boronic Acids↗