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PubMed2002

Influence of boron supplementation on vertebral and femoral bone mass in rats on strenuous treadmill exercise. A morphometric, densitometric, and histomorphometric study.

We studied the effect of boron supplement on experimental osteopenia caused by strenuous exercise in 93- d-old female Wistar rats. A control group of 15 rats was not manipulated. The exercise group of 30 rats was divided into 2 groups of 15 rats each, one that was fed a diet supplemented with 50 mg/kg of boron in the form of Na(2)B(4)O(7), and other that, did not receive a boron supplement. The length and weight were determined in the femur and fifth lumbar vertebra and the bone mineral content and density were assessed through densitometry, and trabecular bone volume, trabecular number, trabecular thickness, and trabecular separation with histomorphometry. The femur length and weight, and vertebra weight, and femur and vertebra bone mineral content and density were significantly lower and the trabecular separation was higher in the exercise group than in the others (p < 0.005 in all). The femur weight, bone mineral content and density, trabecular bone volume and trabecular thickness, were significantly higher in the exercise plus boron group (p < 0.005 to 0.0001). It was concluded that boron preserves bone mass in rats that have been exposed to intense exercise.

Absorptiometry, Photon↗
PubMed2001

Effect of dietary boron on growth performance, calcium and phosphorus metabolism, and bone mechanical properties in growing barrows.

An experiment was conducted to evaluate the effects of dietary boron (B) on growth performance, bone mechanical properties, and calcium (Ca) and phosphorus (P) metabolism in pigs. Thirty-six barrows were weaned at approximately 21 d of age and randomly assigned to receive one of three dietary treatments. Treatments consisted of 1) low-B basal diet (control), 2) basal + 5 mg B/kg diet, and 3) basal + 15 mg B/kg diet. Boron was supplemented as sodium borate. Barrows remained on their respective experimental diets throughout the nursery (35 d) and growing (30 d) phases of production. Blood samples were obtained from each barrow at the end of each phase. Following the 30-d growing period, eight barrows per treatment were transferred to stainless steel metabolism crates. Barrows had an adjustment period of 7 d, followed by a 7-d total collection of urine and feces. All barrows were fed at 90% of the previous ad libitum grower intake of the control animals during the adjustment and collection periods. At the end of the 7-d collection period, barrows were killed and femurs and fibulas were harvested for the assessment of bone mechanical properties. During the nursery phase, ADG and ADFI were increased (P < 0.05) by B supplementation. Boron did not affect (P = 0.34) feed efficiency during the nursery phase. During the growing phase, ADG and ADFI were increased (P < 0.05) by B supplementation. Boron did not affect (P = 0.97) feed efficiency during the growing phase. Boron did not affect (P = 0.44) bone ash percentage, but B supplementation increased (P < 0.05) bone ash P. Ultimate shear force of the fibula was increased (P < 0.05) in barrows supplemented with 15 mg B/kg diet compared to barrows fed diets supplemented with 5 mg B/kg diet. Apparent absorption and retention of Ca and P were not affected (P > 0.05) by dietary B. These data indicate that B supplementation to pigs can increase growth and bone strength without greatly affecting Ca and P metabolism.

Animal Nutritional Physiological Phenomena↗
PubMed1991

Possible alteration of the blood-brain barrier by boron-neutron capture therapy.

In the course of re-assessment of boron-neutron capture therapy (BNCT) for malignant brain tumors, fractionation of neutron irradiation has been proposed. The authors have used BNCT with a single fraction technique during the past 21 years and now decided to study some effects of fractionation. Twenty-two healthy mouse brains were irradiated with thermal neutrons after boron-10 injection (mercaptoundecahydrododecaborate). A second dose of boron-10 was administered and its uptake in the boron-neutron-capture-irradiated brains was determined. A tendency towards increased boron uptake in the moderately BNCT-treated brains was noticed, which may result in increased brain damage if fractionated neutron irradiation is used.

Animals↗
PubMedDate not supplied

Comparative in vitro evaluation of dequalinium B, a new boron carrier for neutron capture therapy (NCT).

A boronated derivative of dequalinium, a delocalized lipophilic cation (DLC), was synthesized as a potential boron carrier for the selective targeting of mitochondria in malignant versus benign cells for boron neutron capture therapy (BNCT), a binary modality for the treatment of cancer. This agent, designated DEQ-B, was taken up and retained in vitro in the KB, F98, and C6 tumor cell lines but not in the normal epithelial cell line CV1. DEQ-B was also less toxic in the latter cell line at lower exposure concentrations The uptake, retention, and toxicity profiles of DEQ-B are comparable to those of the non-boronated DLCs, dequalinium, MKT 077, RH 123, and tetraphenylphosphonium chloride. Our results suggest that the synthesis and further evaluation of boronated DLCs as potential delivery agents for BNCT is warranted.

Animals↗
PubMed2002

Convection-enhanced delivery of boronated epidermal growth factor for molecular targeting of EGF receptor-positive gliomas.

Convection enhanced delivery (CED) is potentially a powerful method to improvethe targeting of macromolecules to the central nervous system by applying a pressure gradient to establish bulk flow through the brain interstitium during infusion. The purpose of the present study was to evaluate CED as a means to improve the intracerebral and intratumoral (i.t.) uptake of a heavily boronated macromolecule (dendrimer; BD) linked to epidermal growth factor (EGF) for neutron capture therapy in rats bearing a syngeneic epidermal growth factor receptor (EGFR) + glioma. Boronated EGF was radiolabeled with 125I and administered by CED at a rate of 0.33 micro l/min for 15, 30, and 60 min [infusion volumes (V(I)) of 5, 10, and 20 micro l, respectively], using a syringe pump connected to an indwelling cannula implanted into the right caudate nucleus of normal rats or i.t. in rats bearing either F98(EGFR) or F98 wild-type (F98(WT)) gliomas. After infusion, rats were euthanized, and their brains were removed and serially sectioned. The uptake and biodistribution of (125)I-boronated EGF in tumor or brain was studied by quantitative autoradiography and gamma-scintillation counting. The volume of distribution (V(d)) in brain was assessed using a computer interfaced image analysis system. After CED, the V(d) increased from 34.4 to 123.5 micro l with corresponding V(i) ranging from 5 to 20 micro l. The V(d) of BD-EGF in the brain was 64.8 +/- 13.4 micro l with CED (V(i) 10 micro ), and the V(d):V(i) ratio was 6.5 compared with a V(d) of 9.4 +/- 1.6 micro l and a V(d):V(i) ratio of 0.9 after direct intracerebral injection. As determined by quantitative autoradiography and gamma-scintillation counting at 24 h after CED, 47.4% of the injected dose per gram tissue (%ID/g) was localized in F98(EGFR) gliomas compared with 33.2%ID/g after direct i.t. injection and 12.3%ID/g in F98(WT) gliomas. On the basis of these observations, we have concluded that CED is more effective than i.t. injection as a way to deliver boronated EGF to EGFR (+) gliomas for boron neutron capture therapy.

Animals↗
PubMedDate not supplied

Determination of boron in silicon-doped gallium arsenide by electrothermal atomic absorption spectrometry and ultraviolet-visible spectrophotometry.

Two methods have been developed for the determination of boron impurities in silicon-doped gallium arsenide (GaAs) for electronics. The first method employs the electrothermal atomic absorption spectrometry (ETAAS), the second, the UV-Vis molecular absorption spectrophotomety. In both cases the GaAs sample is decomposed with aqua regia (1+1). To prevent Ga(III) interference on the ETAAS determination of boron, a double extraction of the chlorogallic acid (HGaCl4) in diethyl ether is performed. To improve the overall ETAAS performance, the graphite tubes were pre-treated with iridium(III) and tungsten(IV). A mixed chemical modifier containing Ni(II), Sr(II) and citric acid was also used. The characteristic mass (m0) is 301 +/- 47 pg and the detection limit (3sB) is 2.4 microg g(-1). The classic UV-Vis spectrophotometric procedure using curcumin was also extended to the determination of boron in GaAs. By masking Ga(III) with EDTA and a preliminary extraction of boron with 2-ethyl-hexane 1,3-diol, performed on a semi-micro scale, a detection limit of 0.6 microg g(-1) was achieved. Both methods were applied to the analysis of two Si-doped GaAs samples which were suspected of being boron-contaminated. Results are compared with those obtained by direct analysis of the decomposed sample solution using the inductively coupled plasma atomic emission spectrometry (ICP-AES).

Arsenicals↗
PubMed2004

Boron and selenium contamination in south Texas groundwater.

Boron and selenium concentrations from 112 water wells in an irrigated agricultural region of south Texas were compiled, mapped, and statistically analyzed. Wells in the study area produce water from the Gulf Coast Aquifer System, comprising coastward sloping beds of clay, silt, sand, and gravel. Nearly 84 percent of boron observations exceeded the 600 ug/L advisory level for drinking water, 70% exceeded the 1250 ug/L level for sensitive crops, and 24% exceeded the 3750 ug/L level for tolerant crops. Additionally, 21% of selenium observations exceeded the 20 ug/L advisory level for irrigation water, and five percent surpassed the 50 ug/L standard for drinking water. Many wells with high boron concentrations also had high selenium concentrations, and several clusters of high concentrations were in irrigated parts of the study area. However, there was no association between selenium and well depth, and a direct rather than inverse association between boron and well depth. Progressively brackish water in downdip reaches of the aquifer largely controls observed boron patterns. Both irrigation practices and prevailing groundwater chemistry significantly influence selenium concentrations in the study area.

Aluminum Silicates↗
PubMed2005

Combination of boron and gadolinium compounds for neutron capture therapy. An in vitro study.

In neutron capture therapy, the therapeutic effect of the boron compound is based on alpha particles produced by the B(n, alpha) reaction while with the gadolinium compound the main radiation effect is from gamma rays derived from the Gd(n, gamma) reaction. The uptake and distribution within the tumor may be different among these compounds. Thus, the combination of the boron and gadolinium compounds may be beneficial for enhancing the radiation dose to the tumor. Chinese hamster fibroblast V79 cells were used. For the neutron targeting compounds, 10B (BSH) at 0, 5, 10, and 15 ppm, and 157Gd (Gd-BOPTA) at 0, 800, 1600, 2400, 3200, and 4800 ppm, were combined. The neutron irradiation was performed with thermal neutrons for 30 min. (neutron flux: 0.84 x 10(8) n/cm2/s in free air). The combination of the boron and gadolinium compounds showed an additive effect when the gadolinium concentration was lower than 1600 ppm. This additive effect decreased as a function of gadolinium concentration at 2400 ppm and resulted in no additive effect at more than 3200 ppm of gadolinium. In conclusion, the combination of the boron and gadolinium compounds can enhance the therapeutic effect with an optimum concentration ratio. When the gadolinium concentration is too high, it may weaken the boron neutron capture reaction due to the high cross-section of gadolinium compound against neutrons.

Animals↗
PubMed1992

Microdosimetry for boron neutron capture therapy.

Preclinical studies for boron neutron capture therapy (BNCT) using epithermal neutrons are ongoing at several laboratories. The absorbed dose in tumor cells is a function of the thermal neutron flux at depth, the microscopic boron concentration, and the size of the cell. Dosimetry is therefore complicated by the admixture of thermal, epithermal, and fast neutrons, plus gamma rays, and the array of secondary high-linear-energy-transfer particles produced within the patient from neutron interactions. Microdosimetry can be a viable technique for determining absorbed dose and radiation quality. A 2.5-cm-diameter tissue-equivalent gas proportional counter has been built with 50 parts per million (ppm) 10B incorporated into the walls and counting gas to simulate the boron uptake anticipated in tumors. Measurements of lineal energy (y) spectra for BNCT in simulated volumes of 1-10 microns diameter show a dose enhancement factor of 4.3 for 30 ppm boron, and a "y" of 250 keV/microns for the boron capture process. Chamber design plus details of experimental and calculated linear energy spectra will be presented.

Boron↗
PubMed2006

[Effects of irradiance on boron requirement of phaseolus aureus cutting for its adventitious root development].

This paper studied the boron requirement of Phaseolus aureus cutting for its adventitious root development under different photosynthetic active radiation (PAR). The results showed that exogenous boron supply was necessary for the adventitious root development of the cutting under 10 days of PAR at 50 or 100 micromol x m(-2) x s(-1), but unnecessary under 6 days of this irradiance and followed by 4 days of darkness. Exogenous boron supply was also necessary for the rooting under 6 days of PAR at 180 micromol x m(-2) x s(-1) and followed by 4 days of darkness. When the PAR at 100 micromol x m(-2) x s(-1) was employed for 10 days, the amount of soluble boron in each hypocotyl of the cutting was only half of that under 6 days of this irradiance and followed by 4 days of darkness, which might be the reason of the necessity of exogenous boron supply for the rooting under 10 days of PAR at 100 micromol x m(-2) x s(-1).

Boron↗
PubMed1991

Boron neutron capture therapy of a murine melanoma with p-boronophenylalanine: dose-response analysis using a morbidity index.

Boron-10 concentrations of 20 or 40 micrograms/g were attained in mouse B16 melanomas following one or two intragastric doses of p-boronophenylalanine (750 mg/kg body weight per dose), respectively. Tumor-to-normal-tissue (blood, muscle) boron concentration ratios were 4:1-6:1. The efficacy of boron neutron capture irradiation was monitored using the Wilcoxon two-sample test in conjunction with a system of ranking outcomes of different therapies that compared living mice and mice sacrificed because of excessive tumor growth concomitantly. Median survivals were extended progressively as radiation doses were increased up to 38.7 gray-equivalent (gray X relative biological effectiveness), with one of five and one of six tumors cured in each of the two highest dose groups, respectively. When comparable tumor inhibitory doses of 250-kVp X rays were used to treat these tumors, instead of the transient erythema and edema that resulted from boron neutron capture therapy, there resulted irreversible muscle necrosis in the irradiated zone and atrophy of the foot distal to the irradiated zone. The improvement in treatment outcome with boron neutron capture therapy is attributable to unprecedented tumor-to-normal-tissue radiation dose ratios of approximately 2.8 to 3.6.

Animals↗
PubMed1987

Preliminary study for application of anti-alpha-fetoprotein monoclonal antibody to boron-neutron capture therapy.

Boron-neutron capture therapy (BNCT) has been applied clinically, especially in brain-neuro surgery. We intended to expand the application of BNCT for the treatment of abdominal cancers and tried to determine whether MoAb (monoclonal antibody) against AFP (alpha-fetoprotein) could be useful tool to deliver boron-10 (10B) to AH-66 hepatoma cells for BNCT. Firstly, MoAb was boronated by mixing with 10B-compound (Cs2 10B12H11SH) by using N-succinimidyl 3(2-pyridyldithio)propionate (SPDP). Numbers of 10B atoms bound to an antibody molecule were in proportion to the dose of 10B-compound added, and maximum number of 10B atoms conjugated to an antibody molecule was approximately 1240. Secondly, using this boronated MoAb, 10B was delivered to AH-66 cells, and 11 X 10(9) 10B atoms were estimated to be on and/or in an AH-66 cell. After the irradiation with thermal neutron, boronated AH-66 cells showed decreasing uptake of [3H]TdR in proportion to the number of 10B atoms bound to and/or incorporated into the tumor cells. These results indicate that 10B atoms delivered by MoAb exert cytotoxic effect on AH-66 cells in a dose dependent manner by thermal neutron irradiation.

Animals↗
PubMed1989

[Boron in dental hard tissues studied by 11B(p,alpha)8Be nuclear reaction].

Boron's low atomic number and low concentration make its measurement in hard dental tissues difficult. Using nuclear reaction, the 11B(p,alpha)8Be*, enamel, dentine and radicular cement of 18 dental elements, ten healthy and eight decayed teeth, both permanent and deciduous were studied. The highest Boron concentrations were found in the two most superficial microns of the vestibular enamel in non-decayed incisors, particularly deciduous ones. Premolar and molar teeth showed lower Boron concentrations than frontal ones, decayed teeth revealed hardly any Boron. In confirmation of the prevailing exogenous contribution of this karyostatic trace element, on average, Boron concentrations were 2.5 times as high as dentine and 10 times as high as cement.

Boron↗
PubMed1987

The Monte Carlo simulation of the biological effect of the 10B(n, alpha)7Li reaction in cells and tissue and its implication for boron neutron capture therapy.

The energy deposition in the nucleus of cells exposed to the 10B(n, alpha)7Li neutron capture reaction has been calculated and compared to the measured biological effect of this reaction. It was found that a considerable distribution of hit sizes to the nucleus occurs. The comparison of hit size frequency with the observed survival indicates that not every hit, independent of its size, can lead to cell death. This implies the existence of a hit size effectiveness function. The analysis shows that the location of boron relative to the radiation-sensitive volume of the cell is of great importance and that average dose values alone are of limited use for predicting the biological effect of this reaction. Boron accumulating in the cell nucleus is much more efficient in cell killing than the same amount of boron uniformly distributed; its presence in one cell, however, has little effect on its neighboring cells in a tissue. When boron is present on the cell surface of a tissue (as presumably delivered by antibodies), its cell-killing effect is greatly reduced compared to that in uniform distribution. However, in this case much of the dose to one cell comes from neutron capture reactions occurring on the surface of its neighbor cells. These data have implications for the choice of boron carries in neutron capture therapy. The mathematical analysis carried out here is similar to that proposed recently for low-level exposure effects of radiation, taking mutation and/or carcinogenesis as biological effects. The results here show that high-level exposure to high-LET particles (resulting in cell killing) should be treated in an analogous manner.

Animals↗
PubMed1983

A calorimetric investigation of the binding of indole and phenylethane boronic acid to chymotrypsin.

The heat of formation of the chymotrypsin-phenylethane boronic acid complex has been observed calorimetrically from pH 4 to 8 at 25 degrees C and is found to be pH-dependent, changing from near -6 kcal/mol at pH 4 to -13 kcal/mol at pH 8. The heat of formation of the chymotrypsin-indole complex is a nearly constant -6 kcal/mol over most of the same pH range. alpha-Chymotrypsin has been purified by pH gradient elution from an immobilized lima bean inhibitor column. Solutions of the enzyme up to 400 microM, prepared in this manner, have a zero heat of dilution from pH 5 to 8 in 0.1 M KCl, with or without added 0.05 M Tris, N-(tris[hydroxy-methyl]methyl-2-amino) ethanesulfonic acid, 4-morpholineethanesulfonic acid, or acetate buffers. Binding of phenylethane boronic acid causes a pH-dependent decrease in proton binding to chymotrypsin; the decrease in proton binding evoked by formation of the indole complex is much less, with a much smaller pH dependence. The calorimetric and proton-binding results are applied to a model for boronic acid binding (Hanai, K. (1976) J. Biochem. (Tokyo) 79, 107-116). We conclude that the thermodynamics of formation of the trigonal boronic acid complex are quite similar to those for the formation of the noncovalent complex formed by indole and related ligands. The trigonal-tetrahedral tautomerism in the boronic acid-chymotrypsin complex is characterized by thermodynamic changes similar to those accompanying the binding of virtual substrates to chymotrypsin.

Boronic Acids↗
PubMed1993

The effect of boron on plasma membrane electron transport and associated proton secretion by cultured carrot cells.

Plasma membrane electron transport reactions and associated proton secretion were studied in boron-deficient carrot cells. It was found that the hormone-sensitive plasma membrane NADH oxidase was inhibited by boron deficiency and that under such conditions activity could be restored by exogenous boric acid with or without 2,4-dichlorophenoxy acetic acid. Gramicidin, a channel-forming protonophore, further stimulated NADH oxidase by carrot cells. Proton secretion, associated with plasma membrane H(+)-ATPase, was also affected by boron deficiency, but not as severely as ferricyanide-generated proton secretion, reflecting plasma membrane electron transport. The addition of 1 mM boric acid and 1 microM 2,4-dichlorophenoxy acetic acid to carrot cells fully restored the H+ secretion in presence of ferricyanide. The effect of boron deficiency in cultured carrot cells can, therefore, be directly associated with cell growth through its effect on the plasma membrane NADH oxidase and H+ secretion. Ferricyanide provides a probe which activates transmembrane electron transport that is only coupled to proton release when boron is present.

2,4-Dichlorophenoxyacetic Acid↗
PubMedDate not supplied

Critical evaluation of bispecific antibodies as targeting agents for boron neutron capture therapy of brain tumors.

Boron neutron capture therapy (BNCT) is based on the nuclear capture reaction that occurs when 10B, a stable isotope, is irradiated with low energy neutrons to produce high linear energy transfer (LET) alpha particles and recoiling 7Li nuclei. In order for BNCT to be successful in treating cancer, approximately 10(9) boron atoms must be delivered per tumor cell to sustain a lethal 10B, (n,a) 7Li capture reaction. In the present study, we have produced and characterized a bispecific antibody (BsAbB8), which was reactive with both human glioma and melanoma cell lines, as well as with a variety of polyhedral borane anions (PBA). The affinity constants (KA) of BsAb-B8 with D-54 MG and M21 cells were 3.49 and 2.57 x 10(8) M-1, respectively, which were almost identical to those of the parental mAb 9.2.27 with these cell lines. In vivo tumor localizing properties were studied in nude mice bearing subcutaneous xenografts of the D-54 MG glioma. Following intravenous injection of 131I-labeled BsAb-B8, 3.4 +/- 0.2% of the injected dose/g was detected in the tumor at 24 hours, and then slowly declined to 2.0 +/- 0.4% at 96 hours compared to 1.34 +/- 0.07% and 0.03 +/- 0.01%, respectively, for normal mouse IgG. Based on the assumption that all the tumor cell antigenic receptor sites could be saturated, the following calculations have been carried out. The maximum concentration of BsAb-B8 that could be delivered to 1 g of D-54 MG glioma cells would be 99.6 micrograms, which could bind 71.7 ng of a PBA. However, since at least 500 x more boron would be required per gram of tumor to sustain a lethal 10B (n,a) 7Li capture reaction, a macromolecule containing -10(3)-10(4) boron atoms rather than a low molecular weight PBA would be required to deliver this amount. Such boron containing macromolecules have been synthesized by us, and future studies should provide information on the feasibility of using them in combination with BsAb-B8 to deliver the requisite amount of 10B.

Animals↗
PubMed2004

Enhanced blood boron concentration estimation for BPA-F mediated BNCT.

The blood boron concentration regulates directly the BNCT irradiation time in which the prescribed dose to the patient is delivered. Therefore a proper estimation of the blood boron concentration for the treatment field based on the measured blood samples before irradiation is required. The bi-exponential model fit using Levenberg-Marquardt method was implemented for this purpose to provide the blood boron concentration estimates directly to the treatment data flow during the BNCT procedure. The harmonic mean bi-exponential decay half-lives of the studied patient data (n=28) were 15+/-8 and 320+/-70 min for the faster and slower half-life. The model uncertainty (n=28) was reasonably low, 0.7+/-0.1 microg/g (about 5%). The implemented algorithm provides a robust method for temporal blood boron concentration estimation for BPA-F mediated BNCT. Utilization of the infusion data improves the reliability of the estimate. The overall data flow during the treatment fulfills the practical requirements concerning the BNCT procedure.

Algorithms↗