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At least 703 records · Page 39Linked to original sources
PubMed1996

Comet assay study of DNA damage and repair of tumour cells following boron neutron capture irradiation with fast d(14) + Be neutrons.

We compared the amount of radiation-induced DNA damage and the extent of DNA repair in human melanoma cells (MeWo) using the 'comet assay' after neutron, boron neutron capture and X-irradiation. Using a colony-forming assay it was shown earlier that lethal effects in tumour cells treated with fast neutrons may be increased by the neutron capture reaction 10B(n, alpha)7Li. The effectiveness of boron neutron capture in killing tumour cells depends on the number of 10B atoms delivered to the tumour, the subcellular distribution of 10B and the thermal neutron fluence at the side of the tumour. Using the 'comet assay' the DNA damage of fast neutrons (mean energy 5.8 MeV) was shown to be significantly greater than for the same absorbed dose of X-rays. The presence of 600 ppm 10B (boric acid H5 10BO3) in the cell medium during irradiation with d(14) + Be neutrons in a phantom enhances the DNA damage by 20% compared with neutron irradiation alone. After DNA damage induction by neutrons and neutron capture of boron, the DNA repair capacity of the MeWo cells is significantly reduced in comparison with X-irradiation resulting in proportionally more residual DNA damage after 180 min of repair time.

Boron Neutron Capture Therapy↗
PubMed1998

Uptake, toxicity and radiation effects of the boron compounds DAAC-1 and DAC-1 in cultured human glioma cells.

PURPOSE: To study the uptake, toxicity and radiation effects in vitro of a diol-amino acid-carborane (DAAC-1) and make comparisons with the previously studied diol-amine-carborane (DAC-1). MATERIALS AND METHODS: Toxicity and radiation effects were studied with clonogenic survival, uptake by measuring the cellular boron content and the subcellular distribution was investigated after organelle separation with centrifugation. The studied cell line was human glioma U343. RESULTS: DAAC-1 showed an accumulation of 1-1.5 times, compared with the culture medium, and was non-toxic up to 47 microg boron/ml. The accumulation of DAC-1 was about 90 times, but toxic effects were detectable already at the concentration 5 microg boron/ml. None of the compounds was localized in the cell nucleus. Following irradiation with thermal neutrons, DAC-1 was about 2.5 times more effective than DAAC-1 and about 4.9 times more effective than neutrons alone, at the survival level 0.2. The dose modifying factors, when compared with the neutron beam alone, were for both DAAC-1 and DAC-1 about 1.5 and about 5 when compared with 60Co-gamma-radiation. CONCLUSIONS: DAAC-1 was less toxic than DAC-1 but gave less accumulation of boron. Both substances gave significant boron-dependent cell inactivation when the test cells were exposed to thermal neutrons.

Boranes↗
PubMed1989

Do inert beta-lactamase inhibitors act as synergizers of beta-lactam antibiotics? Utility of boric and boronic acids.

Boric and boronic acids were used as inhibitors of beta-lactamases produced by two Citrobacter diversus strains and by one strain of Pseudomonas aeruginosa; all strains were clinical isolates. The beta-lactamases produced by the two Citrobacter diversus strains were inhibited by both borates and boronates, using cephazolin as substrate. The enzyme from Pseudomonas aeruginosa was inhibited only by boronates, using benzylpenicillin as substrate. These inhibitors were also used in combination with selected beta-lactams so as to determine if a synergism of antimicrobial activity occurred. All data reported in the present paper indicate that the minimum inhibitory concentration (MIC) values were lowered in the presence of these inhibitors for the two Citrobacter diversus strains. In the Pseudomonas aeruginosa strains the MIC values were not significantly altered, thus indicating the presence of a permeability barrier for 3-aminophenylboronic acid.

Anti-Bacterial Agents↗
PubMed1991

A history of boron neutron capture therapy of brain tumours. Postulation of a brain radiation dose tolerance limit.

Boron neutron capture therapy (BNCT) is a form of radiation therapy mediated by the short-range (less than 10 microns) energetic alpha (4He) and lithium-7 (7Li) ionizing particles that result from the prompt disintegration by slow neutrons of the stable (nonradioactive) nucleus boron-10 (10B). Recent advances in radiobiological and toxicological evaluation of tumour-affinitive boron-containing drugs and in optimization of the energies of neutrons in the incident beam have spurred interest in BNCT. This article presents a history of BNCT that emphasizes studies in the USA. A new dosimetric analysis of the 1959-1961 clinical trials of BNCT at Brookhaven National Laboratory is also presented. This analysis yields an acute radiation dose tolerance limit estimate of approximately 10 Gy-Eq to the capillary endothelium of human basal ganglia from BNCT. (Gy-Eq: Gray-equivalent, or relative biological effectiveness of a radiation component multiplied by the physical dose of the component (Gy), summed over the component kinds of radiation.)

Boron↗
PubMedDate not supplied

Use of cyclic boronates for GC/MS screening and quantitation of beta-adrenergic blockers and some bronchodilators.

Gas chromatographic and mass spectrometric properties of cyclic methyl and n-butyl boronates of 13 beta blockers and bronchodilators were investigated for potential use in screening and quantitation in biological materials of interest. The tested compounds included acebutolol, atenolol, labetalol, levobunolol, metoprolol, nadolol, oxprenolol, pindolol, propranolol, sotalol, albuterol, and isoproterenol. The cyclic methyl boronates were superior in gas chromatographic properties to the corresponding n-butylboronates of these compounds. Higher weights of fragments obtained with n-butyl boronation may be advantageous for analyses of complex biological matrices. Mass spectra and retention times relative to SKF-525A are provided.

Adrenergic beta-Antagonists↗
PubMed2004

High energy-resolution electron energy-loss spectroscopy study of the electronic structures of Li- and Mg-doped alpha-rhombohedral boron.

Electron-doped alpha-rhombohedral boron (alpha-r-B) crystals were synthesized by Li- and Mg-dopings. The doped alpha-r-B particles showed a shiny metallic colour, though non-doped alpha-r-B crystals showed a dark red colour (red boron). The electronic structures of doped alpha-r-B single crystals were examined by a high energy-resolution electron energy-loss spectroscopy microscope. Boron 1s electron-excitation spectra, which show the density of states of the conduction bands, of Li-doped alpha-r-B showed a chemical shift toward a smaller binding-energy side, indicating a charge transfer from the doped atoms to alpha-r-B. These spectra also showed a sharp intensity increase at the onset with a width of an energy resolution of the experiment. The sharp intensity increase may be assigned to a Fermi edge produced by the electron doping. The spectra of Mg-doped alpha-r-B showed a chemical shift indicating an electron doping, but did not show the presence of a Fermi edge.

Boron↗
PubMed1990

Boron neutron capture therapy of a rat glioma.

The purpose of the present study was to utilize a well-established rat glioma to evaluate boron neutron capture therapy for the treatment of malignant brain tumors. Boron-10 (10B) is a stable isotope which, when irradiated with thermal neutrons, produces a capture reaction yielding high linear energy transfer particles (10B + 1nth----[11B]----4He(alpha) + 7Li + 2.79 MeV). The F98 tumor is an anaplastic glioma of CD Fischer rat origin with an aggressive biological behavior similar to that of human glioblastoma multiforme. F98 cells were implanted intracerebrally into the caudate nuclei of Fischer rats. Seven to 12 days later the boron-10-enriched polyhedral borane, Na2B12H11SH, was administered intravenously at a dose of 50 mg/kg body weight at varying time intervals ranging from 3 to 23.5 hours before neutron irradiation. Pharmacokinetic studies revealed blood 10B values ranging from 0.33 to 10.5 micrograms/ml depending upon the time after administration, a T1/2 of 6.2 hours, normal brain 10B concentrations of 0.5 microgram/g, and tumor values ranging from 1.1 to 12.8 micrograms/g. No therapeutic gain was seen if the capture agent was given at 3 or 6 hours before irradiation with 4 x 10(12) n/cm2 (10 MW-min; 429 cGy). A 13.5-hour preirradiation interval resulted in a mean survival of 37.8 days (P less than 0.01), compared to 30.5 days (P less than 0.03) for irradiated controls and 22.1 days for untreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1967

Experimental microbiology of saturated salt solutions and other harsh environments. 3. Growth of salt-tolerant penicillium notatum in boron-rich media.

A stress-tolerant strain of Penicillium notatum, isolated by passage through a nutrient solution saturated with calcium acetate, was found to have a tolerance to boron in several states of oxidation. Growth in the presence of elementary boron, saturating amounts of boric acid, and with various concentrations of sodium borohydride was observed and mycelial mats were spectrographically analyzed for boron accumulation.

Boron↗
PubMed1996

Peptide boronic acids. Versatile synthetic ligands for affinity chromatography of serine proteinases.

Peptide boronic acids are potent transition-state analogue inhibitors of serine proteinases. We prepared the peptide boronic acids Ala-Ala-boroPhe (AAbF), targeted at chymotrypsin-like proteinases, and Ala-Ala-boroVal (AAbV), targeted at elastolytic enzymes. Analogues protected on the N-terminus with the carbonylbenzyloxy (Cbz) group were powerful inhibitors of human neutrophil elastase (HNE) and human cathepsin G (CatG), as well as the non-human counterparts, porcine pancreatic elastase (PPE) and bovine alpha-chymotrypsin (ChT) Removal of N-Cbz protecting groups and immobilization with Sepharose 6B provided affinity matrices. Columns consisting of the AAbF or AAbV affinity matrix separated a mixture of PPE and ChT. PPE was specifically retained by the AAbV column and ChT was specifically retained by the AAbF column. HNE and CatG were not separated using the AAbF matrix, but were separated with the AAbV matrix. To demonstrate the practical utility of these affinity ligands, HNE was isolated from crude human neutrophil extracts, resulting in an 18-fold purification in one chromatographic step, with a 41% recovery of elastolytic activity. Because peptide boronic acids can be synthesized having specificity for a wide range of target enzymes, this method is readily adaptable as a general procedure for isolation and purification of serine proteinases.

Animals↗
PubMed2005

Boron neutron capture enhancement of fast neutron radiotherapy utilizing a moderated fast neutron beam.

An investigation of the therapeutic potential of boron neutron capture (BNC) enhancement of fast neutron therapy utilizing the Harper University Hospital superconducting cyclotron-produced d(48.5)+Be fast neutron therapy beam is presented. A technique for modification of the fast neutron beam to increase the BNC enhancement is presented along with an evaluation of the effects of beam moderation on the biological effectiveness of the absorbed dose. Characteristics of the photon, neutron, and boron neutron capture components of the absorbed dose are presented. Results demonstrate the possibility of therapeutic gains greater than 50% over conventional fast neutron therapy at depths required to treat brain lesions. This enhancement is estimated assuming currently achievable boron concentrations, and is more than adequate to provide a therapeutic window for the effective treatment of Glioblastoma Multiforme without prohibitive toxicity to the normal brain.

Body Burden↗
PubMed2004

Evaluation of human thymidine kinase 1 substrates as new candidates for boron neutron capture therapy.

Thymidine analogs containing o-carboranylalkyl groups at the 3-position were screened as potential substrates for human thymidine kinase 1 (TK1), an enzyme that is selectively expressed in a variety of rapidly proliferating cells, including tumor cells. On the basis of previous studies, 12 of these were identified as potential delivery agents for boron neutron capture therapy, a therapeutic method used for the treatment of high-grade brain tumors. Compound 4 with a pentylene spacer between the o-carborane cage and the thymidine scaffold and compound 10, which has an additional dihydroxypropyl substituent at the o-carborane cage, were the best substrates for TK1 with kcat/Km values of 27% and 36% relative to that of thymidine, respectively. These compounds showed partial competitive inhibition for thymidine phosphorylation by TK1. Neither compound was a substrate of recombinant human thymidine phosphorylase nor were their respective 5'-monophosphates substrates of 5'-deoxynucleotidase 1, thereby indicating potential in vivo stability. The octanol/water partition coefficient for compound 10 was 2.09, suggesting that it has excellent physiochemical properties for crossing the blood brain barrier and penetrating brain tissue. The in vitro cytotoxic effect of the 12 analogs was moderate to low in mammalian cell cultures with IC50 values between 10 and 160 micromol/L. Compounds 4 and 10 were taken up selectively and retained by the murine fibroblast L929 cell line, in contrast to its TK1-deficient variant. These findings suggest that compound 10 is a promising candidate for selective delivery of boron-10 to malignant cells, and additional in vivo studies are planned to evaluate it for boron neutron capture therapy of brain tumors.

5'-Nucleotidase↗
PubMedDate not supplied

On the inhibitory activities of a new boron compound and ultrasound against the mouse ascites tumour.

The inhibitory effects of a new boron compound, dihydroxy (oxybiguanido) boron (III) hydrochloride monohydrate (HB), and ultrasound (US) of a frequency 25 kHz on the growth of ascites tumour in female Swiss mice were studied by monitoring the survival, weight of tumour-associated material, tumour cell count, serum alkaline phosphatase activity and the haematological parameters of the treated animals. 5-Fluorouracil (5-FU), a well-known anticancer agent, was used as positive control. While HB exhibited a very significant antitumour action, US alone produced a small but significant inhibitory effect. The combination of US with HB or 5-FU produced an extra antitumour action as compared to the actions of these chemicals used singly. The mechanisms of action of the new boron compound (HB) and US are discussed.

Alkaline Phosphatase↗
PubMedDate not supplied

A new boron compound (guanidine biboric acid adduct) as an antitumour agent against Ehrlich ascites carcinoma in mice.

The inhibitory effects of a new boron compound of guanidine biboric acid adduct (GB) and guanidium chloride (L1) on the growth of ascites tumour in female Swiss mice were studied by monitoring the survival, tumour weight, tumour cell count, transplantability of Ehrlich ascites cells, precursor incorporation and the haematological parameters of the treated mice. 5-Fluorouracil, a known anticancer drug, was used as a positive control. The most important parameter was the survival time, which increased significantly when tumour-bearing mice were treated with the boron compound. Haematological parameters of the treated animals showed minimum toxic effects when boron was coupled with guanidine.

Animals↗
PubMed2001

Synthesis, characterization, and magnetic properties of carbon- and boron-oxide-encapsulated iron nanocapsules.

Carbon- and boron-oxide-encapsulated iron nanocapsules have been synthesized by arc discharge in methane (CH4) and diborane (B2H6) atmospheres respectively. The characterization and magnetic properties of carbon- and boron-oxide-encapsulated iron nanocapsules [abbreviated as Fe(C) and Fe(B) respectively] were investigated and compared. The structure of the Fe(B) nanocapsules is different from that of the Fe(C) nanocapsules. The Fe(C) nanocapsules consist of a crystalline graphite shell and a core of alpha-Fe and/or Fe3C. The Fe(B) nanocapsules consist of an amorphous boron-oxide layer and a core of Fe(B) solid solution, alpha-Fe, gamma-Fe, FeB, and/or Fe3B phases. The saturation magnetizations of both the Fe(C) and the Fe(B) nanocapsules below 300 K decrease monotonically with increasing temperature. The coercivities of the Fe(C) and Fe(B) nanocapsules are almost 2 orders of magnitude higher than that of bulk Fe. The temperature dependence of magnetization at high temperatures indicates the existence of some phase transformations.

Borohydrides↗
PubMed1989

Electron spectroscopic imaging for high-resolution immunocytochemistry: use of boronated protein A.

In the present study we adapted electron spectroscopic imaging (ESI) for high-resolution immunocytochemistry. To accomplish this, we applied boronated protein A (B-pA) for indirect detection of specific antigenic sites using pre-embedding and post-embedding protocols. Isolated acinar cells were exposed to wheat germ agglutinin (WGA) and anti-WGA, followed by B-pA, to reveal WGA binding sites at the level of the plasma membrane. The cells were then embedded in Epon and unstained ultra-thin sections were examined by electron microscopy using the ESI mode. For post-embedding, ultra-thin sections of glutaraldehyde-fixed, Lowicryl-embedded pancreatic tissue were exposed to specific antibodies (anti-insulin or anti-amylase), followed by B-pA. The unstained sections were examined using the ESI mode. In both cases, boron was detected with high resolution either at the level of the plasma membrane of acinar cells, demonstrating WGA binding sites, or over secretory granules in pancreatic insulin-secreting cells or acinar cells, demonstrating insulin and amylase, respectively. These findings were compared to those obtained with the protein A-gold technique, and have demonstrated the analogy of both types of labeling. In addition, several control experiments assessed this novel approach. They have demonstrated the specificity of labeling and the high reactivity of B-pA, as well as its antibody-binding properties. Finally, electron energy loss spectral analysis confirmed the presence of boron in the tissue sections at sites where immunolabeling was detected. These results demonstrate that ESI is an appropriate approach for cytochemistry. Since the technique is based on detection of elements, spatial resolution is considered to be in the magnitude of 0.5 nm, which represents a major improvement in resolution over actual electron microscopic cytochemical techniques.

Animals↗
PubMed1994

Cell survival measurements in an argon, aluminium and sulphur filtered neutron beam: a comparison with 24 keV neutrons and relevance to boron neutron capture therapy.

Boron neutron capture therapy (BNCT) has been advanced as a suitable alternative therapy for the treatment of glioma. BNCT involves the selective uptake of a tumour with a boron-bearing substance and subsequent irradiation with a beam of neutrons. Previous attempts with BNCT have utilized thermal neutrons, but this involves resection of the scalp prior to treatment and is only possible with superficial tumours. An alternative is to use a beam of intermediate-energy neutrons which will produce a peak in the thermal neutron fluence at depth in tissue and so enable deep-seated tumours to be treated. A neutron beam with a mean energy of approximately 9 keV, obtained by filtering neutrons from a reactor with aluminium, argon and sulphur, has been used to explore the radiobiological advantage over thermal and 24 keV neutrons for BNCT. Irradiation of V79 and HeLa cells at various positions in a polythene phantom suggest that the beam is less cytotoxic for a given neutron fluence than the 24 keV neutron beam previously considered as an alternative to thermal neutrons for BNCT. However, optimization of boron distribution via the development of new compounds still appears to be necessary for BNCT to become a safe alternative option for the treatment of glioma.

Aluminum↗
PubMed1976

Toxic and gonadotropic effects of cadmium and boron relative to standards for these substances in drinking water.

Experimental research was conducted on the study of the relationship of the general toxic and gonadotoxic effects of cadmium and boron under conditions of subacute and chronic oral intoxication on white random-bred rats, by use of biochemical, physiological, cytological, and pathomorphological methods. It is shown that the gonadotoxic effect of cadmium is manifested on the same level (3 mg/kg of body weight) as the general toxic effect. The gonadotoxic effect of boron is dominant and is manifested at a lower level (6 mg/kg of body weight) than the general toxic effect (20 mg/kg). On the basis of the results of chronic experiments, 0.001 mg/l. is recommended as the hygienic standard for cadmium in water and 0.5 mg/l. for boron.

Animals↗
PubMed2004

Endogenous lithium and boron red cell-plasma ratios: normal subjects versus bipolar patients not on lithium therapy.

This study was undertaken to compare endogenous lithium concentrations in human blood and its components from normal donors versus bipolar patients. The patients were not on lithium therapy at the time that the blood samples were donated and had not received any lithium therapy for at least 2 yr. Blood components were separated by centrifugation. The analytical method for lithium as developed in this laboratory consists of thermal-neutron activation of freeze-dried samples. 3H is produced via the reaction 6Li + n = 3H + 4He, and high-sensitivity rare gas mass spectrometry is used to measure 3He formed from beta-decay of 3H. Boron measurements are made concurrently using 4He from the reaction 10B + n = 4He + 7Li. Seven normal donors and seven patients with a diagnosis of bipolar disorder participated in this study. Measurements of lithium and boron were made in whole blood, plasma, and red cells. Red cell-plasma ratios R(Li) and R(B) were calculated after corrections were made for trapped plasma in the red cells. The results show that bipolar patients may have higher concentrations of lithium in blood, plasma, and red cells (p = 0.08, 0.02, and 0.02, respectively) and may have higher R(Li) values than normal donors (p = 0.01). No evidence was found for bipolar-normal differences in these four parameters for boron. Although our sample size is admittedly very small, the results clearly show that the endogenous red cell ratio R(Li) and plasma or red cell lithium concentrations may become useful diagnostic indicators for bipolar illness if the analytical methods are further developed.

Adult↗