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PubMed1988

Capillary permeability and boron distribution in ethylnitrosourea-induced rat glioma.

The vasculature and capillary permeability of gliomas induced by ethylnitrosourea in Sprague-Dawley rats were studied with horseradish peroxidase and Evans blue dye. The distribution of the boron-10 compound, Na2(10)B12H11SH, which is now in clinical use for boron neutron capture therapy (BNCT) for brain tumors, was investigated quantitatively using neutron-induced alpha-autoradiography. The vasculature and the degree of capillary permeability varied widely, depending mainly on the size of the glioma, and were often heterogeneous even in the same tumor. The distribution of boron-10 also varied, correlating to capillary permeability. The boron-10 concentration and the tumor:blood concentration ratio in large and medium-sized gliomas were adequate for successful BNCT. This study suggests that the vasculature and capillary permeability of the target brain tumor exert an important influence on the therapeutic efficacy of BNCT.

Animals↗
PubMed1994

Biodistribution of boron in dogs with spontaneous intracranial tumors following borocaptate sodium administration.

Borocaptate sodium (Na2B12H11SH) is a potentially useful compound for boron neutron capture therapy of intracranial tumors. Tumor and normal tissue boron concentrations were evaluated in 30 dogs with naturally occurring intracranial tumors after i.v. borocaptate sodium infusion (55 mg boron/kg). Postmortem tissue boron concentrations were measured for three postinfusion time periods (2, 6, and 12 h) by inductively coupled plasma atomic emission spectroscopy. Mean boron concentrations for extracerebral tumors were 40.6 +/- 16.9 (2 h; n = 8), 25.9 +/- 11.7 (6 h; n = 5), and 8.6 +/- 4.5 micrograms boron/g (12 h; n = 6). Mean boron concentrations for intracerebral tumors were 30.6 +/- 17.5 (2 h; n = 7) and 2.9 +/- 1.8 micrograms boron/g (6 h; n = 4). Mean tumor boron concentrations were lower at longer postinfusion times. The tumor:normal brain boron concentration ranged from 0.8 to 19.8. Tumor:blood boron concentrations were less than one for all but three dogs and ranged from 0.04 to 1.4. Mean peritumor boron concentrations were highly variable but exceeded that of normal brain in 10 of 20 dogs. In some dogs, the mean peritumor boron concentration was similar to or exceeded the tumor boron concentration. Distant or contralateral normal brain had consistently low boron concentrations. Some cranial and systemic tissues had high boron concentrations, indicating substantial extravascular boron. The spontaneous animal tumors provided a realistic spectrum of data and enabled extensive sampling of diseased and normal tissues. The biodistribution of boron from borocaptate sodium administration was partially favorable because of high tumor boron concentrations. Empirical radiation dose tolerance studies should be used to determine the impact of the unfavorably high boron concentration of blood and some cranial tissues.

Adenoma↗
PubMed2002

Towards more chemically robust polymer-supported chiral catalysts for the reactions of aldehydes with dialkylzincs.

N-Methyl-alpha,alpha-diphenyl-L-prolinol derivatives with para-bromo substituents in one or both of the phenyl rings are easily bound to crosslinked polystyrene beads containing phenylboronic acid residues using Suzuki reactions. When the products were used as catalysts for the reactions of aldehydes with diethylzinc in toluene at 20 degrees C, the alcohols were produced in chemical yields >90% and with ees of upto 94%. The better of the two supported catalysts gave ees only 0-9% lower than those obtained with the corresponding soluble catalyst. One of the supported catalysts was recycled successfully nine times.

Alcohols↗
PubMed2000

Diazaborine resistance in yeast involves the efflux pumps Ycf1p and Flr1p and is enhanced by a gain-of-function allele of gene YAP1.

We have found that YAP1-mediated diazaborine resistance in the yeast Saccharomyces cerevisiae requires two efflux pumps, i.e. the major-facilitator-superfamily transporter Flr1p, which is located in the cytoplasmic membrane and the ATP-binding-cassette transporter Ycf1p which is present in the vacuolar membrane. Both these transporters are known to be under the control of the transcriptional transactivator Yap1p which explains our earlier finding that overexpression of YAP1 mediates diazaborine resistance. Overexpression of YAP1 in a Deltaflr1Deltaycf1 double disruptant strain does not mediate any diazaborine resistance, showing that these pumps are the only ones involved in detoxification of this drug. We also found a new mechanism of diazaborine resistance which is caused by an allelic form of YAP1, designated YAP1-11. This allele of YAP1 carries a mutation that leads to a C620F exchange in the C-terminal cysteine-rich-domain region and is the first mutant of YAP1 that was isolated by a conventional genetic screen for drug resistance. The protein encoded by the gain-of-function allele may transactivate by a different mechanism from the wild-type protein when overexpressed because it does not enhance YCF1 mRNA and still mediates diazaborine resistance in a Deltaflr1Deltaycf1 background.

ATP-Binding Cassette Transporters↗
PubMed2002

Coronal microleakage of five materials used to create an intracoronal seal in endodontically treated teeth.

The purpose of this study was to quantitatively compare the sealing effectiveness of five restorative materials that were used to create an intracoronal double seal. Fifty-two extracted mandibular molars were randomly divided into five groups of 10 teeth, and one positive and one negative control tooth. The crowns were removed and the pulpal floor and canal orifices were sealed with 3 mm of one of the following materials: Amalgabond, C&B Metabond, One-Step Dentin Adhesive with AEliteflo composite, One-Step with Palfique composite, or intermediate restorative material (IRM). Each tooth was affixed to a fluid filtration device and the seal was evaluated at 0, 1, 7, 30, and 90 days. The results showed a significant (p = 0.0001) difference in leakage between the materials. At 7 days, IRM, AEliteflo, and Palfique leaked significantly more than Amalgabond or C&B Metabond. Amalgabond consistently produced the best seal of all the materials throughout the duration of the study.

Barium Compounds↗
PubMed2006

Cadmium is acutely toxic for murine hepatocytes: effects on intracellular free Ca(2+) homeostasis.

We studied cadmium toxicity in murine hepatocytes in vitro. Cadmium effects on intracellular free Ca(2+) concentration ([Ca(2+)](i)) were assayed, using a laser scanning confocal microscope with a fluorescent probe, Fluo-3/AM. The results showed that administration of cadmium chloride (CdCl(2), 5, 10, 25 microM) resulted in a dose-dependent decrease of hepatocyte viability and an elevated aspartate aminotransferase (AST) activity in the culture medium (p<0.05 for 25 microM CdCl(2) vs. control). Significant increases of lactate dehydrogenase (LDH) activities in 10 and 25 microM CdC1(2)-exposed groups were observed (p<0.05 and p<0.01, respectively). A greatly decreased albumin content and a more malondialdehyde (MDA) formation also occurred after CdC1(2) treatment. The Ca(2+) concentrations in the culture medium of CdCl(2)-exposed hepatocytes were significantly decreased, while [Ca(2+)](i) appeared to be significantly elevated (p<0.05 or p<0.01 vs. control). We found that in Ca(2+)-containing hydroxyethyl piperazine ethanesulfonic acid-buffered salt solution (HBSS) only, CdCl(2) elicited [Ca(2+)](i) increases, which comprised an initially slow ascent and a strong elevated phase. However, in Ca(2+)-containing HBSS with addition of 2-aminoethoxydiphenyl borane (2-APB), CdCl(2) caused a mild [Ca(2+)](i) elevation in the absence of an initial rise phase. Removal of extracellular Ca(2+) showed that CdCl(2) induced an initially slow [Ca(2+)](i) rise alone without being followed by a markedly elevated phase, but in a Ca(2+)-free HBSS with addition of 2-APB, CdCl(2) failed to elicit the [Ca(2+)](i) elevation. These results suggest that abnormal Ca(2+) homeostasis due to cadmium may be an important mechanism of the development of the toxic effect in murine hepatocytes. [Ca(2+)](i) elevation in acutely cadmium-exposed hepatocytes is closely related to the extracellular Ca(2+) entry and an excessive release of Ca(2+) from intracellular stores.

Albumins↗
PubMed2003

Effect of reinforcement methods on the retention of resin-bonded fixed partial dentures using a composite denture tooth as a pontic: in vitro evaluation.

PURPOSE: The incorporation of composite denture teeth as pontics in resin-bonded fixed partial dentures has been deemed to be short-lived. This study investigated whether pre- or posttreatments could improve the bonding of denture tooth pontics. MATERIALS AND METHODS: A model fixed partial denture was fabricated that included composite denture teeth (Endura) bonded with 1 of 2 resin systems (C&B-Metabond or Aeliteflo). The bonding surface of the pontic was pretreated with one of three methods (air-particle abrasion [AA], AA plus silanization, or cavity preparation plus AA). The bonding areas between pontic and abutments were posttreated with 1 of 2 methods (reinforcement with fiber or metal post). Five bonded specimens for each treatment group were subjected to 20,000 thermocycles (40 degrees C to 60 degrees C; dwell time 60 s) before retentive forces (N) were determined. All data were analyzed with two-way ANOVA and Bonferroni's test (p = 0.05). RESULTS: All specimens that underwent the pre- and posttreatment outperformed untreated specimens. For the specimens bonded with C&B-Metabond and posttreated with a polyethylene fiber (Ribbond) or a metal post (DC Post), the mean retentive forces were 316 N and 301 N for mandibular specimens, and 354 N and 380 N for maxillary specimens, respectively. These values were significantly higher than those obtained with other pretreatment methods (p < or = 0.0003). For mandibular specimens bonded with Aeliteflo, specimens posttreated with Ribbond exhibited significantly higher retentive forces (332 N) compared to other specimens (p < or = 0.0001). CONCLUSION: Within the limitations of this study, the bond strength of a resin-bonded fixed partial denture incorporating a composite denture tooth as the pontic was improved by reinforcement with either a polyethylene fiber or a metal post.

Analysis of Variance↗
PubMed1998

Distribution and excretion of boron after intravenous administration of disodium mercaptoundecahydro-closo-dodecaborate to rats.

Disodium mercaptoundecahydro-closo-dodecaborate (BSH) is an important compound for boron neutron capture therapy. The pharmacokinetics of boron by BSH were studied in normal rats after rapid intravenous injection at three doses (30, 100, 300 mg/kg) or continuous infusion (100 mg/kg/30 min). The boron concentration in biological samples was measured by inductively coupled plasma atomic emission spectroscopy. The blood half-lives of boron in the elimination phase (t1/2 beta) after rapid injection of BSH at doses of 30, 100 and 300 mg/kg were 1.7, 17 and 19 hr, respectively. AUC (32, 219 and 4030 micrograms.hr/ml) increased with the dose, but there was no proportionality among the values. Total clearance decreased drastically from 233 ml/hr/kg (100 mg/kg) to 38 ml/hr/kg (300 mg/kg). As boron was excreted mainly into urine, these results suggest that renal function failure might occur with dosing of 300 mg/kg. In the case of continuous infusion of 100 mg/kg of BSH for 30 min, the pharmacokinetic parameters were similar to those of rapid injection of 100 mg/kg. The highest boron concentration was observed in the kidney and the lowest in the brain. After multiple dosing of BSH at 100 mg/kg/day x 14 days, the boron concentrations in blood, liver, lung and kidney at 24 hr after the last dosing were higher than those after single dosing and were similar to those of simulated values calculated from the single dosing parameters. These results clearly indicated that boron does not accumulate unexpectedly in any tissue with multiple dosing of 100 mg/kg of BSH for two weeks.

Animals↗
PubMedDate not supplied

Boron neutron capture therapy of primary and metastatic brain tumors.

Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when a stable isotope, boron-10, is irradiated with low energy (0.025 eV) thermal neutrons (nth) to yield alpha (4He) particles and 7Li nuclei (10B+nth-->[11B]-->4He + 7Li + 2.79 MeV). The success of BNCT as a tumoricidal modality is dependent on the delivery of a sufficient quantity of 10B and nth to individual cancer cells to sustain a lethal 10B(n, alpha) 7Li reaction. Boron delivery agents include a variety of compounds, such as the sulfhydryl containing polyhedral borane sodium borocaptate (Na2B12H11SH, [BSH]), boronoporphyrins, boronophenylalanine, carboranyl uridines (CBU), and boronated monoclonal antibodies (MAb). The present review will focus on three delivery systems that currently are under investigation in our laboratories, boronated monoclonal antibodies, carboranyl uridines, and boronophenylalanine. Methodology has been developed to heavily boronate MAb using a precision macromolecule, a "starburst" dendrimer, which can be linked to MAb by means of heterobifunctional reagents. Although the resulting immunoconjugates retain their in vitro immunoreactivity, they lose their in vivo tumor localizing properties and accumulate in the liver. In order to obviate this problem, work is now in progress to produce bispecific MAb, which can simultaneously recognize a tumor-associated antigen and a boronated macromolecule. Boron containing nucleosides are potential vehicles for incorporating boron compounds into nucleic acids of neoplastic cells. For this purpose, carboranyl uridines have been synthesized with the boron moiety on either the pyrimidine base or on the carbohydrate component. Although such structures appear to be avidly taken up and retained by tumor cells in vitro, only the 5-carboranyl-nucleosides are converted biologically to the nucleotide. There is no evidence, however, that the latter are incorporated into nucleic acids. Other carboranyl nucleosides currently are being synthesized that may have better tumor localizing properties. The potential use of boronophenylalanine as a capture agent for the treatment of melanoma metastatic to the brain also is under investigation. A nude rat model has been developed using human melanoma cells that are stereotactically implanted into the brain. BNCT-treated animals have either had prolonged survival times or continue to live compared to control rats that invariably died of their tumors, thereby suggesting therapeutic efficacy.

Animals↗