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PubMed1994

Oral toxicity of boric acid and other boron compounds to immature cat fleas (Siphonaptera: Pulicidae).

Oral toxicity was characterized in first-instar cat fleas, Ctenocephalides felis felis (Bouché), feeding on dried blood treated with boric acid. LC50 values ranged from 2.11% after 24 h to 0.21% after 7 d. In carpet tests with five different boron compounds and a number of different formulations, significant mortality for first instars was observed in all cases. In similar tests with prepupae and cocoons, there was no significant effect on mortality. The importance of these results is discussed in light of current application procedures for boron compounds, and suggestions are made for future research.

Administration, Oral↗
PubMed1996

Deliberations and evaluations of the approaches, endpoints and paradigms for boron, chromium and fluoride dietary recommendations.

The 10th edition (1989) of the Recommended Dietary Allowances provided estimated safe and adequate daily dietary intakes (ESADDI) for chromium and fluoride and summarized the substantial evidence for boron essentiality in animals. New endpoints, approaches and paradigms to use to formulate dietary guidance for these elements were reviewed by a discussion group that met as part of a national workshop. Deliberations of the group are summarized to facilitate future discussions on dietary guidance for these elements. The category, "provisional RDA" was recommended to replace the current ESADDI category because of the ambiguities associated with the ESADDI. A provisional RDA would be defined for a dietary substance that meets one of two sets of criteria: class 1, clear evidence of essentiality but uncertain or limited quantitative data or endpoints to define dietary requirements; and class 2, strong evidence of essentiality, and clear nutritional benefit based on reasonably certain quantitative data, but lack of clear information on function or endpoints to use for deficiency dietary requirements. A summary of background information and possible approaches for assigning provisional RDAs for boron, chromium and fluoride is presented.

Boron↗
PubMed2000

Boron supplementation of a semipurified diet for weanling pigs improves feed efficiency and bone strength characteristics and alters plasma lipid metabolites.

Two experiments were conducted to determine effects of dietary boron (B) on performance, plasma minerals and metabolites, and bone characteristics in young pigs. In Experiment 1, 48 pigs (24 males, 24 females; 21 d old) were allotted to pens, which were randomly assigned to one of the following dietary treatments: 1) control (natural ingredient diet; 6.7 mg B/kg diet), 2) control + 5 mg B/kg diet and 3) control + 15 mg B/kg diet. Boron was supplemented as sodium borate. In Experiment 2, 48 pigs (24 males, 24 females; 21 d old) were assigned to the same treatments described in Experiment 1; however, the basal diet was a semipurified diet (0.98 mg B/kg diet). Diets were fed for 40 d; on d 40, blood samples were obtained for determination of plasma mineral and metabolite concentrations. Femurs were harvested from 8 pigs per treatment on d 40 for determination of mechanical properties, ash and lipid percentage. In Experiment 1, B did not affect performance, plasma minerals or metabolites or bone properties. In Experiment 2, B supplementation improved (P: < 0.05) the gain:feed ratio and increased plasma cholesterol and triglyceride concentrations. There was a treatment x sex interaction (P: < 0.05) in Experiment 2 for bone lipid to be lower and bending moment to be higher, with the response occurring in male pigs. Other dependent variables in Experiment 2 were not affected by treatment. In conclusion, B supplementation of a low B diet elicited responses of physiologic importance to pigs. However, B supplementation of a natural ingredient diet did not elicit a response.

Alkaline Phosphatase↗
PubMed1997

Direct PCR sequencing with boronated nucleotides.

A method is described to simultaneously amplify and sequence DNA using a new class of nucleotides containing boron. During the polymerase chain reaction, boron-modified nucleotides, i.e. 2'-deoxynucleoside 5'-alpha-[P-borano]-triphosphates, are incorporated into the product DNA. The boranophosphate linkages are resistant to nucleases and thus the positions of the boranophosphates can be revealed by exonuclease digestion, thereby generating a set of fragments that defines the DNA sequence. The boranophosphate method offers an alternative to current PCR sequencing methods. Single-sided primer extension with dideoxynucleotide chain terminators is avoided, with the consequence that the sequencing fragments are derived directly from the original PCR products. Boranophosphate sequencing is demonstrated with the Pharmacia and the Applied Biosystems 373A automatic sequencers, producing data that is comparable with cycle sequencing.

Bacteriophage T7↗
PubMed2005

Filter, collimator and moderating material to achieve boron neutron capture enhanced fast neutron therapy.

The combination of fast neutron therapy and boron neutron capture therapy is currently being studied as a possible treatment for some radio-resistant brain tumours. In an attempt to design a boron-enhanced fast neutron therapy beam for the Fermilab Fast Neutron Therapy Facility, the use of moderating material surrounding the patient's head has been investigated. Graphite, polyethylene, water and heavy water were studied as moderating materials, using MCNP. The use of tungsten, iron, lead and bismuth as materials for a small filter and collimator near the patient's head was investigated. Calculations showed that a filter and collimator made of tungsten with a graphite moderator was capable of producing a dose enhancement of 17.3 +/- 0.6% for a 100 microg g(-1) loading of 10B for a 5.6 cm diameter beam while delivering 1.5 Gy in 7 min.

Boron Neutron Capture Therapy↗
PubMed2004

Boron retranslocation in Scots pine and Norway spruce.

We previously traced 10B-enriched boric acid from shoots to roots to demonstrate the translocation of boron (B) in Scots pine (Pinus sylvestris L.) and Norway spruce (Picea abies (L.) Karst.) seedlings. To gain a more detailed understanding of B translocation, we sought: (1) to demonstrate B retranslocation directly, by showing that foliar-applied 10B is located in the new growth after dormancy; and (2) to assess whether shoot-applied B affects growth in the long term. We applied 10B-enriched boric acid to needles of Scots pine and Norway spruce seedlings. After a dormancy period and 9 weeks of growth, small but significant increases in the 10B isotope were found in the new stem and needles of both species. In Scots pine, the total B concentration of the new stem was also increased. Both species contained polyols, particularly pinitol and inositol. Boron-polyol complexes may provide a mechanism for mobilizing B in these species. To determine the long-term effects of applied B, seedlings were grown for two growing seasons after the application of 10B to shoots. In Norway spruce, the proportion of 10B in the root systems and current needles of the harvest year was slightly higher than in the controls, and in Scots pine root systems, marginally so. The B treatment had no effect on growth of Norway spruce seedlings. In Scots pine seedlings, the B treatment caused a 33% increase in total dry mass and significantly increased the number of side branches.

Boron↗
PubMed1982

Neutron dosimetry by the spark counting of tracks in boron-doped film.

Thin cellulose nitrate films are doped with a boron compound. After thermal neutron irradiation, the films are etched in an aqueous solution of 10% NaOH, at 50 degrees C, for 1.5 hr, during which the 27 microns thick films are reduced to about 7 microns. The etch-pits caused by 10B(n, alpha)7Li reactions are punched twice at 600 V and then counted at 500 V. The ratio of the spark density to the thermal neutron fluence was found to be 1.0 X 10(-4) for a boron concentration of 1%. After due consideration of background counts, a thermal neutron dose of 0.3 mrem (3 X 10(-6) Sv) can be measured with this system.

Boron↗
PubMed2005

A comparison of the COG and MCNP codes in computational neutron capture therapy modeling, Part I: boron neutron capture therapy models.

The goal of this study was to evaluate the COG Monte Carlo radiation transport code, developed and tested by Lawrence Livermore National Laboratory, for neutron capture therapy related modeling. A boron neutron capture therapy model was analyzed comparing COG calculational results to results from the widely used MCNP4B (Monte Carlo N-Particle) transport code. The approach for computing neutron fluence rate and each dose component relevant in boron neutron capture therapy is described, and calculated values are shown in detail. The differences between the COG and MCNP predictions are qualified and quantified. The differences are generally small and suggest that the COG code can be applied for BNCT research related problems.

Body Burden↗
PubMed2006

Structure of the Mycobacterium tuberculosis proteasome and mechanism of inhibition by a peptidyl boronate.

Mycobacterium tuberculosis (Mtb) has the remarkable ability to resist killing by human macrophages. The 750 kDa proteasome, not available in most eubacteria except Actinomycetes, appears to contribute to Mtb's resistance. The crystal structure of the Mtb proteasome at 3.0 A resolution reveals a substrate-binding pocket with composite features of the distinct beta1, beta2 and beta5 substrate binding sites of eukaryotic proteasomes, accounting for the broad specificity of the Mtb proteasome towards oligopeptides described in the companion article [Lin et al. (2006), Mol Microbiol doi:10.1111/j.1365-2958.2005.05035.x]. The substrate entrance at the end of the cylindrical proteasome appears open in the crystal structure due to partial disorder of the alpha-subunit N-terminal residues. However, cryo-electron microscopy of the core particle reveals a closed end, compatible with the density observed in negative-staining electron microscopy that depended on the presence of the N-terminal octapetides of the alpha-subunits in the companion article, suggesting that the Mtb proteasome has a gated structure. We determine for the first time the proteasomal inhibition mechanism of the dipeptidyl boronate N-(4-morpholine)carbonyl-beta-(1-naphthyl)-L-alanine-L-leucine boronic acid (MLN-273), an analogue of the antimyeloma drug bortezomib. The structure improves prospects for designing Mtb-specific proteasomal inhibitors as a novel approach to chemotherapy of tuberculosis.

Binding Sites↗
PubMedDate not supplied

Neutron-induced gamma dose from a reactor beam filter for boron neutron capture therapy.

For the boron neutron capture therapy (NCT) of deep-seated metastatic melanoma, an epithermal (up to a few keV energy) neutron beam from a reactor horizontal facility could be useful if the inherent contamination from fast neutrons and gamma rays could be minimised. Calculations for ANSTO's 10 MW research reactor HIFAR have shown that, even though a filter material such as AlF3 attenuates the fast neutron dose, the beam quality improvement is counteracted by a relative increase in the gamma dose because of the gammas arising from neutron captures in the filter material, particularly the aluminium. The aluminium gammas, most of which arise from thermal neutron capture, are hard and cannot be attenuated by lead or bismuth without comparable attenuation of the epithermal neutron flux. Addition of an absorber such as 6Li to the AlF3 filter was investigated as a means of reducing the hard gamma dose, but the improvement in beam quality was small and at considerable cost to dose intensity. Dose characteristics calculations confirmed the superiority of a tangential beam over a radial beam with better results from an unfiltered tangential beam than from an AlF3 filter in a radial beam. This study showed conclusively that assessments of filter assemblies based on the effect of individual components on either the neutron or gamma dose in isolation are inadequate. In assessing any epithermal neutron filter, thermal neutron shield, and gamma shield combination, the total effect of each on the neutron, gamma, and boron-10 dose must be considered.

Boron↗
PubMedDate not supplied

Preclinical and phase I studies of monoclonal antibodies in melanoma: application to boron neutron capture therapy of melanoma.

Monoclonal antibodies (MAbs) provide an attractive method of selectively localizing sufficient boron atoms around tumour cells to capture neutrons. Assuming that 10(8)-10(10) 10B atoms are needed for one capture event and that 10(3)-10(4) atoms can be coupled to each antibody molecule, then 10(5)-10(6) antibody molecules gathered on an individual cell will destroy that cell. Binding to normal tissues, on the other hand, would need to be at least 20-fold less than that to tumour tissues to avoid toxic effects of neutrons on surrounding tissues. Preclinical studies in animals show that several MAbs may bind to melanoma cells in sufficient quantities in vitro to localize the required amount of Boron per cell. Whether this will occur in vivo, however, may depend not only on antigen density but a variety of other properties of the tumour cells and MAbs. These include the Ig class and affinity of the antibody and whether the antibody is internalized into the tumour cell. The ratio of uptake between tumour and normal tissue is governed by such factors as the percentage of tumour cells within a tumour expressing the antigen and whether the MAb react with normal tissues. Use of Fab or F(ab)2 preparations of the MAb may increase the uptake ratio by preventing uptake of MAb by cells with Fc receptors. In contrast to preclinical animal studies, tumour/normal tissue uptake ratios in phase I studies in humans have been disappointingly low.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

A trial to improve the analysis of boron in biological materials.

For the spectrophotometric determination of boron in biological materials, two decomposition methods were used. One is the alkali fusion method, and the other is the acid decomposition method using a uniseal decomposition vessel. A long-range calibration curve for the former method was obtained by using an ultrapure sulfuric acid. The alkali fusion method was applied to samples into which paraboronophenylalanine (BPA) or its hydrochloric salt (BPA.HCl) had been injected. By the acid decomposition method using a uniseal vessel, 50 mg dried liver was digested by a mixed solution of 1 ml conc. sulfuric acid and 6 ml 30% hydrogen peroxide. A problem exists, however, in that the hydrogen peroxide remaining in the decomposition solution must be eliminated without loss of boron.

Alkalies↗
PubMed2004

Advantage and limitations of weighting factors and weighted dose quantities and their units in boron neutron capture therapy.

Defining the parameters influencing the biological reaction due to absorbed dose is a continuous topic of research. The main goal of radiobiological research is to translate the measurable dose of ionizing radiation to a quantitative expression of biological effect. Mathematical models based on different biological approaches (e.g., skin reaction, cell culture) provide some estimations that are often misleading and, to some extent, dangerous. Conventional radiotherapy is the simplest case because the primary radiation and secondary radiation are both low linear energy transfer (LET) radiation and have about the same relative biological effectiveness (RBE). Nevertheless, for this one-dose-component case, the dose-effect curves are not linear. In fact, the total absorbed dose and the absorbed dose per fraction as well as the time schedule of the fractionation scheme influence the biological effects. Mathematical models such as the linear-quadratic model can only approximate biological effects. With regard to biological effects, fast neutron therapy is more complex than conventional radiotherapy. Fast neutron beams are always contaminated by gamma rays. As a consequence, biological effects are due to two components, a high-LET component (neutrons) and a low-LET component (photons). A straight transfer of knowledge from conventional radiotherapy to fast neutron therapy is, therefore, not possible: RBE depends on the delivered dose and several other parameters. For dose reporting, the European protocol for fast neutron dosimetry recommends that the total absorbed dose with gamma-ray absorbed dose in brackets is stated. However, boron neutron capture therapy (BNCT) is an even more complex case, because the total absorbed dose is due to four dose components with different LET and RBE. In addition, the terminology and units used by the different BNCT groups is confusing: absorbed dose and weighted dose are both to be stated in grays and are never "photon equivalent." The ICRU/IAEA made proposals, which should be followed by all BNCT groups, to report always the four absorbed dose components, boron dose DB, proton dose Dp, gamma-ray dose Dgamma, and neutron dose Dn, as well as the sum DT of all components, as total absorbed dose, together with the total weighted dose Dw (to be used only for internal purposes, indicating the used weighting factors) at all points of interest and the treatment conditions.

Body Burden↗
PubMed2005

An international dosimetry exchange for boron neutron capture therapy. Part I: Absorbed dose measurements.

An international collaboration was organized to undertake a dosimetry exchange to enable the future combination of clinical data from different centers conducting neutron capture therapy trials. As a first step (Part I) the dosimetry group from the Americas, represented by MIT, visited the clinical centers at Studsvik (Sweden), VTT Espoo (Finland), and the Nuclear Research Institute (NRI) at Rez (Czech Republic). A combined VTT/NRI group reciprocated with a visit to MIT. Each participant performed a series of dosimetry measurements under equivalent irradiation conditions using methods appropriate to their clinical protocols. This entailed in-air measurements and dose versus depth measurements in a large water phantom. Thermal neutron flux as well as fast neutron and photon absorbed dose rates were measured. Satisfactory agreement in determining absorbed dose within the experimental uncertainties was obtained between the different groups although the measurement uncertainties are large, ranging between 3% and 30% depending upon the dose component and the depth of measurement. To improve the precision in the specification of absorbed dose amongst the participants, the individually measured dose components were normalized to the results from a single method. Assuming a boron concentration of 15 microg g(-1) that is typical of concentrations realized clinically with the boron delivery compound boronophenylalanine-fructose, systematic discrepancies in the specification of the total biologically weighted dose of up to 10% were apparent between the different groups. The results from these measurements will be used in future to normalize treatment plan calculations between the different clinical dosimetry protocols as Part II of this study.

Biophysical Phenomena↗
PubMedDate not supplied

Boron neutron capture therapy for the treatment of cerebral gliomas. I. Theoretical evaluation of the efficacy of various neutron beams.

The technique of boron neutron capture therapy in the treatment of cerebral gliomas depends upon the selective loading of the tumor with a 10B-enriched compound and subsequent irradiation of the brain with low-energy neutrons. The charged particles produced in the 10B (n,alpha) 7Li reaction have ranges in tissue of less than 10 mum so that the dose distribution closely follows the 10B distribution even to the cellular level. The effectiveness of this therapy procedure is dependent not only on the 10B compound but on the spectral characteristics of the neutron source as well. Hence, an optimization of these characteristics will increase the chances of therapeutic success. Transport calculations using a neutral particle transport code have been made to determine the dose-depth distributions within a simple head phantom for five different incident neutron beams. Comparison of these beams to determine their relative therapeutic efficacy was made by the use of a maximum useable depth criterion. In particular, with presently available compounds, the MIT reactor (MITR) therapy beam (a) is not inferior to a pure thermal neutron beam, (b) would be marginally improved if its gamma-ray contamination were eliminated, (c) is superior to a partially 10B-filtered MITR beam, and (d) produces a maximum useable depth which is strongly dependent upon the tumor-to-blood ratio of 10B concentrations and weakly dependent upon the absolute 10B concentration in tumor. A pure epithermal neutron beam with a mean energy of 37 eV is shown to have close to the optimal characteristics for boron neutron capture therapy. Futhermore, these optimal characteristics can be approximated by a judiciously D2O moderated and 10B-filtered 252Cf neutron source. This tailored 252Cf source would have at least a 1.5 cm greater maximum useable depth than the MITR therapy beam for realistic 10B concentrations. However, at least one gram of 252Cf would be needed to make this a practical therapy source. If the moderated 252Cf source is not 10B filtered, the resultant neutron beam has characteristics similar to those of the MITR beam with no gamma-ray contamination. For usch a beam, 100 mg of 252Cf would produce a flux of 2.4 X 10(8) neutrons/(cm2 sec), which is an intensity suitable for therapy applications.

Boron↗
PubMed2000

A Monte Carlo dosimetry-based evaluation of the 7Li(p,n)7Be reaction near threshold for accelerator boron neutron capture therapy.

Advanced methods of boron neutron capture therapy (BNCT) use an epithermal neutron beam in conjunction with tumor-targeting boron compounds for irradiation of glioblastomas and metastatic melanomas. A common neutron-producing reaction considered for accelerator-based BNCT is 7Li(p,n)7Be, whose cross section increases very rapidly within several tens of keV of the reaction threshold at 1.88 MeV. Operation in the proton energy region near threshold will have an appreciable thick target neutron yield, but the neutrons produced will have relatively low energies that require little moderation to reach the epithermal range desirable for BNCT. Because of its relatively low projected accelerator cost and the portability of the neutron source/target assembly, BNCT based on the near-threshold technique is considered an attractive candidate for widespread hospital use. A systematic Monte Carlo N-Particle (MCNP) investigation of the dosimetric properties of near-threshold neutron beams has been performed. Results of these studies indicate that accelerator proton energies between 1.93 and 1.99 MeV, using 5 cm of H2O moderator followed by thin 6Li and Pb shields, can provide therapeutically useful beams with treatment times less than one hour and accelerator currents less than 5 mA.

Beryllium↗
PubMed2000

Computational validation of the stereology principle applied to the microdosimetry of boron neutron capture therapy.

High resolution quantitative autoradiography (HRQAR) is a novel technique that has been developed in our laboratory and applied to the microdosimetry of boron neutron capture therapy (BNCT). High resolution quantitative autoradiography is employed to define the microdistribution of boron-10 atoms within a 1-2 microm frozen tissue section. This microdistribution is used as input to a novel two-dimensional Monte Carlo charged particle transport calculation that computes various microdosimetric parameters, such as the number of nuclear "hits," energy absorbed in the nuclei, etc., within the environment of actual tissue morphology (i.e., cell nuclei, cytoplasm, and intracellular space). Stereological transformation is then implemented to transform the two-dimensional calculations into effectively three-dimensional results. In the present study no seek to demonstrate the validity of the surrogate two-dimensional 2-D computation as being quantitatively equivalent to a hypothetical full 3-D calculation. The results show that within the limitations of the test parameters used the surrogate 2-D and 3-D results are completely equivalent within the statistical constraints of the Monte Carlo calculations. Limitations of this approach also are evaluated, including a Monte Carlo calculation of the influence of the thickness of the histological tissue section and the track detector and the influence of 4He and 7Li particle lateral and range straggling.

Algorithms↗
PubMed2006

Physicochemical and antimicrobial properties of boron-complexed polyglycerol-chitosan dendrimers.

A polyglycerol with dendritic structure (PGLD) was synthesized by ring-opening polymerization of deprotonated glycidol using a polyglycerol as core functionality in a step-growth process. Then, PGLD reacted with O-carboxymethylated chitosan to obtain PGLD-chitosan dendrimer (PGLD-Ch). After the reaction of PGLD-Ch with boric acid, there was a marked increase in the bulk viscosity evidencing physically that boron can initiate a charge transfer complex formation, (PGLD-Ch)B. Gel permeation chromatography analysis was used to characterize the molecular weight and the polydispersivity of the synthesized PGLD-Ch. A dendritic structure with a molecular mass of 16.7 kDa and a narrow polydispersity (Mw/Mn = 1.05) was obtained. 1H-NMR and 13C-NMR measurements were employed to assess the degree of branching in PGLD. The obtained value of 0.85 indicates the tendency toward a dentritic structure for PGLD. The glass transition temperature values of (PGLD-Ch)B membranes containing 10% and 30% PGLD were -19 degrees C and -26 degrees C, respectively, which favor its potential use as surface coating of several polymers. The in vitro cytotoxicity was evaluated using the minimum essential medium elution test assay. Extracts of boron-complexed PGLD exhibited lower cytotoxicity than the controls, suggesting that the material has an improved biocompatibility. Antibacterial studies of (PGLD-Ch)B against Staphylococcus aureus and Pseudomonas aeruginosa showed a significant activity. Our study confirms and supports the effectiveness of (PGLD-Ch)B as an antimicrobial coating due to its capacity in suppressing the bacterial proliferation. The best in vivo response was found for (PGLD-Ch)B-30 membranes, which exhibited higher synthesis of collagen fibers than PGLD-ChB-10.

Animals↗