Synthesis and in vivo murine evaluation of Na4[1-(1'-B10H9)-6-SHB10H8] as a potential agent for boron neutron capture therapy. (1/283)

Reaction of the normal isomer of [B20H18]2- and the protected thiol anion, [SC(O)OC(CH3)3]-, produces an unexpected isomer of [B20H17SC(O)OC(CH3)3]4- directly and in good yield. The isomer produced under mild conditions is characterized by an apical-apical boron atom intercage connection as well as the location of the thiol substituent on an equatorial belt adjacent to the terminal boron apex. Although the formation of this isomer from nucleophilic attack of the normal isomer of [B20H18]2- has not been reported previously, the isomeric assignment has been unambiguously confirmed by one-dimensional and two-dimensional 11B NMR spectroscopy. Deprotection of the thiol substituent under acidic conditions produces a protonated intermediate, [B20H18SH]3-, which can be deprotonated with a suitable base to yield the desired product, [B20H17SH]4-. The sodium salt of the resulting [B20H17SH]4- ion has been encapsulated in small, unilamellar liposomes, which are capable of delivering their contents selectively to tumors in vivo, and investigated as a potential agent for boron neutron capture therapy. The biodistribution of boron was determined after intravenous injection of the liposomal suspension into BALB/c mice bearing EMT6 mammary adenocarcinoma. At low injected doses, the tumor boron concentration increased throughout the time-course experiment, resulting in a maximum observed boron concentration of 46.7 micrograms of B per g of tumor at 48 h and a tumor to blood boron ratio of 7.7. The boron concentration obtained in the tumor corresponds to 22.2% injected dose (i.d.) per g of tissue, a value analogous to the most promising polyhedral borane anions investigated for liposomal delivery and subsequent application in boron neutron capture therapy.  (+info)

Chronic feeding of a low boron diet adversely affects reproduction and development in Xenopus laevis. (2/283)

The aims of this work were as follows: 1) to determine whether a purified diet currently used for studies with rats was acceptable for reproductive studies in frogs; and 2) to determine whether frogs are sensitive to a deficit of boron (B) in the diet. Adult Xenopus laevis were fed a nonpurified beef liver and lung (BLL) diet (310 microg B/kg), a purified diet supplemented with boron (+B; 1850 microg B/kg), or a purified diet low in boron (-B; 45 microg B/kg) for 120 d. Frogs fed the BLL and +B diets produced 11.3 and 12.2% necrotic eggs, respectively. Abnormal gastrulation occurred in <4% of the fertilized eggs in both groups, and 96-h larval survival exceeded 75% in both groups. In contrast, frogs fed the -B diet for 120 d produced a high proportion of necrotic eggs (54%). Fertilized embryos from the -B diet-fed frogs showed a high frequency of abnormal gastrulation (26.8%), and >80% of the embryos died before 96 h of development. Mean embryo cell counts at X. laevis developmental stage 7.5 (mid-blastula) were significantly lower in the -B embryos than in the BLL or +B embryos. BLL and -B embryos grown in low boron culture media had a high frequency of malformations compared with embryos grown in boron-supplemented media. These studies show that a purified diet that has been used in rodent studies was acceptable for reproduction studies in X. laevis. This work also demonstrates that a diet low in boron markedly impairs normal reproductive function in adult X. laevis, and that administration of the low boron diet results in an increase in both incidence and severity of adverse effects. In addition, these studies demonstrate the usefulness of the X. laevis model in nutrition studies.  (+info)

Natural treatments for osteoarthritis. (3/283)

Osteoarthritis (OA) is the most common form of joint disease. Although OA was previously thought to be a progressive, degenerative disorder, it is now known that spontaneous arrest or reversal of the disease can occur. Conventional medications are often effective for symptom relief, but they can also cause significant side effects and do not slow the progression of the disease. Several natural substances have been shown to be at least as effective as nonsteroidal anti-inflammatory drugs at relieving the symptoms of OA, and preliminary evidence suggests some of these compounds may exert a favorable influence on the course of the disease.  (+info)

The physical characteristics of neodymium iron boron magnets for tooth extrusion. (4/283)

Impaction and non-eruption of teeth is a common problem encountered in orthodontics and many techniques have been proposed for the management of this condition. It has been advocated that a system utilizing magnets would supply a continuous, directionally sensitive, extrusive force, through closed mucosa and thus provide not only a physiological sound basis for successful treatment, but also reduce the need for patient compliance and appliance adjustment. This ex vivo investigation examined in detail the physical characteristics of neodymium iron boron magnets employed in attraction in order to assess their usefulness in the clinical situation. Attractive force and magnetic flux density measurements were recorded for nine sets of magnet pairs with differing morphologies. The effect of spatial relationship on force was assessed by varying vertical, transverse and horizontal positions of the magnets relative to each other, and by altering the pole face angles. The data obtained suggest that magnets with larger pole face areas and longer magnetic axes provide the best performance with respect to clinical usefulness. It was possible to formulate a specific relationship between force and flux density for each magnet pair. This relationship can be used in the clinical management of unerupted teeth to predict the force between the magnets by measuring the magnetic flux density present at mucosal level. The results indicate that magnetic systems may, indeed, have a place in the treatment of unerupted teeth.  (+info)

Boron stimulates yeast (Saccharomyces cerevisiae) growth. (5/283)

Boron is required for the growth of vascular plants and embryonic development in fish. The molecular basis of boron's essentiality, however, remains unknown for both. The objective of this study was to determine whether yeast (Saccharomyces cerevisiae) could be used as a model for the evaluation of intracellular boron trafficking. Three experiments were conducted to assess the effect of boron supplementation on yeast growth. Cultures were grown in low boron media containing 0.04 micromol B/L. After 24 h, a new flask was inoculated with this culture; it was allowed to reach early log phase growth (9 h) and was then divided between two flasks. One flask was supplemented with ultrapure boric acid to achieve a concentration of 185 micromol B/L (+B); the other was supplemented with an equivalent volume of ultrapure water (NB). Boron significantly stimulated cell growth rate into the stationary phase of growth. Yeast cell boron concentrations decreased in both treatments over the course of the experiment, but analysis by inductively coupled plasma-mass spectrometry (ICPMS) did not detect differences in cellular concentration between the boron supplemented (B) and nonsupplemented (NB) groups. Ethanol concentrations did not differ between the two treatments, demonstrating that boron-stimulated growth was not a secondary effect of alcohol dehydrogenase inhibition. The demonstration of boron-dependent growth stimulation in yeast suggests that Saccharomyces cerevisiae can be used as a model system for the study of intracellular boron trafficking.  (+info)

The durability of parylene coatings on neodymium-iron-boron magnets. (6/283)

A parylene coating is frequently used to prevent corrosion of neodymium-iron-boron magnets when they are used intra-orally. This in vitro study was designed to test the durability of parylene coating in a simulated oral environment. Single and double parylene-coated magnets were subjected to grinding and crushing forces in an industrial ball mill. The results demonstrate that abrasion and wear was visible around the edges after 1 hour of testing, with a breach of the coating noted under high magnification scanning electron microscopy (SEM). The conclusion of the study is that parylene coating is unlikely to withstand intra-oral forces. The shape of the magnets, the manufacturing process involved in their production, and the thickness of the parylene coating are important factors to consider with respect to the durability of magnets used in the mouth.  (+info)

Boron microlocalization in oral mucosal tissue: implications for boron neutron capture therapy. (7/283)

Clinical studies of the treatment of glioma and cutaneous melanoma using boron neutron capture therapy (BNCT) are currently taking place in the USA, Europe and Japan. New BNCT clinical facilities are under construction in Finland, Sweden, England and California. The observation of transient acute effects in the oral mucosa of a number of glioma patients involved in the American clinical trials, suggests that radiation damage of the oral mucosa could be a potential complication in future BNCT clinical protocols, involving higher doses and larger irradiation field sizes. The present investigation is the first to use a high resolution surface analytical technique to relate the microdistribution of boron-10 (10B) in the oral mucosa to the biological effectiveness of the 10B(n,alpha)7Li neutron capture reaction in this tissue. The two boron delivery agents used clinically in Europe/Japan and the USA, borocaptate sodium (BSH) and p-boronophenylalanine (BPA), respectively, were evaluated using a rat ventral tongue model. 10B concentrations in various regions of the tongue mucosa were estimated using ion microscopy. In the epithelium, levels of 10B were appreciably lower after the administration of BSH than was the case after BPA. The epithelium:blood 10B partition ratios were 0.2:1 and 1:1 for BSH and BPA respectively. The 10B content of the lamina propria was higher than that measured in the epithelium for both BSH and BPA. The difference was most marked for BSH, where 10B levels were a factor of six higher in the lamina propria than in the epithelium. The concentration of 10B was also measured in blood vessel walls where relatively low levels of accumulation of BSH, as compared with BPA, was demonstrated in blood vessel endothelial cells and muscle. Vessel wall:blood 10B partition ratios were 0.3:1 and 0.9:1 for BSH and BPA respectively. Evaluation of tongue mucosal response (ulceration) to BNC irradiation indicated a considerably reduced radiation sensitivity using BSH as the boron delivery agent relative to BPA. The compound biological effectiveness (CBE) factor for BSH was estimated at 0.29 +/- 0.02. This compares with a previously published CBE factor for BPA of 4.87 +/- 0.16. It was concluded that variations in the microdistribution profile of 10B, using the two boron delivery agents, had a significant effect on the response of oral mucosa to BNC irradiation. From a clinical perspective, based on the findings of the present study, it is probable that potential radiation-induced oral mucositis will be restricted to BNCT protocols involving BPA. However, a thorough high resolution analysis of 10B microdistribution in human oral mucosal tissue, using a technique such as ion microscopy, is a prerequisite for the use of experimentally derived CBE factors in clinical BNCT.  (+info)

Boron supplementation of a semipurified diet for weanling pigs improves feed efficiency and bone strength characteristics and alters plasma lipid metabolites. (8/283)

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.  (+info)

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