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Evaluation of ecological and in vitro effects of boron on prostate cancer risk (United States).

OBJECTIVE: To determine: (1) the correlation of prostate cancer incidence and mortality with groundwater boron and selenium concentrations; and (2) the impact of boron on prostate cancer cell proliferation during co-treatment with alternative chemo-preventative agents, along with boron pre-treatment effects on cell sensitivity to ionizing radiation. METHODS: For regression analysis, data on prostate cancer incidence and mortality were obtained from the Texas Cancer Registry, while groundwater boron and selenium concentrations were derived from the Texas Water Development Board. Cultured DU-145 prostate cancer cells were used to assess the impact of boric acid on cell proliferation when applied in combination with selenomethionine and genistein, or preceding radiation exposure. RESULTS: Groundwater boron levels correlated with a decrease in prostate cancer incidence (R = 0.6) and mortality (R = 0.6) in state planning regions, whereas selenium did not (R = 0.1; R = 0.2). Growth inhibition was greater during combined treatments of boric acid and selenomethionine, or boric acid and genistein, versus singular treatments. 8-day boric acid pre-exposure enhanced the toxicity of ionizing radiation treatment, while dose-dependently decreasing the expression of anti-apoptotic protein Bcl-2. CONCLUSIONS: Increased groundwater boron concentrations, across the state of Texas, correlate with reduced risk of prostate cancer incidence and mortality. Also, boric acid improves the anti-proliferative effectiveness of chemo-preventative agents, selenomethionine and genistein, while enhancing ionizing radiation cell kill.

Anticarcinogenic Agents↗

Determination of the mode and efficacy of the cross-linking of guar by borate using MAS 11B NMR of borate cross-linked guar in combination with solution 11B NMR of model systems.

The reaction product of boric acid and the polysaccharide guaran (the major component of guar gum) has been investigated by 11B NMR spectroscopy. By comparison with the 11B NMR of boric acid and phenylboronic acid complexes of 1,2-diols (HOCMe2CMe2OH, cis-C6H10(OH)2, trans-C6H10(OH)2, o-C6H4(OH)2), 1,3-diols (neol-H2), monosaccharides (L-fucose, mannose and galactose) and disaccharides (cellobiose and sucrose) it is found that the guaran polymer is cross-linked via a borate complex of two 1,2-diols both forming chelate 5-membered ring cycles ([B5(2)]), this contrasts with previous proposals. Based upon steric constraints we propose that preferential cross-linking the guaran polymer occurs via the 3,4-diols of the galactose side chain. The DeltaH and DeltaS for complexation of boric acid to cis- and trans-1,2-cyclohexanediol have been determined, from the temperature dependence of the appropriate equilibrium constants, and used in conjunction with ab initio calculations on model compounds, to understand prior conflicting proposals for guaran-boric acid interactions. 11B NMR derived pH dependent equilibrium constants and ab initio calculations have been used to understand the reasons for the inefficiency of boric acid to cross-link guaran (almost 2 borate ions per 3 monosaccharide repeat units are required for a viscous gel suitable as a fracturing fluid): the most reactive sites on the component saccharides (mannose and galactose) are precluded from reaction by the nature of the guar structure; the comparable acidity (pKa) of the remaining guaran alcohol substituents and the water solvent, results in a competition between cross-linking and borate formation; a significant fraction of the boric acid is ineffective in cross-linking guar due to the modest equilibrium (Keq). In contrast to prior work, we present evidence for the reaction of alcohols with boric acid, rather than the borate anion. Based upon the results obtained for phenylboronic acid, alternative cross-linking agents are proposed.

Boric Acids↗

Effects of boron derivatives on extracellular matrix formation.

Boric acid solution (3%) dramatically improves wound healing through action on the extracellular matrix, a finding that has been obtained in vitro. Consequently, investigations are presently underway to produce boronated compounds having a therapeutical effectiveness similar to that of boric acid. On the basis of experimental results obtained with boric acid, we examined the effects of boron derivatives on extracellular matrix formation and degradation and analyzed their potential toxicity by using two biological models (chick embryo cartilage and human fibroblasts). The four boron derivatives tested in this study (triethanolamine borate; N-diethyl-phosphoramidate-propylboronique acid; 2,2 dimethylhexyl-1,3-propanediol-aminopropylboronate and 1,2 propanediol-aminopropylboronate) mimicked the effects of boric acid. They induced a decrease of intracellular concentrations in extracellular matrix macromolecules (proteoglycans, proteins)-associated with an increase of their release in culture medium and stimulated the activity of intra- and extracellular proteases. Similarly to boric acid, these actions occurred after exposure of the cells to concentrations of all boron derivatives without apparent toxic effects. The compounds were found to be more toxic than boric acid itself when concentrations were calculated according to their molecular weight. Nevertheless, these in vitro preliminary results demonstrate effects of boron derivatives that may be of therapeutic benefit in wound repair.

Animals↗

The Pore Size of Non-Graminaceous Plant Cell Walls Is Rapidly Decreased by Borate Ester Cross-Linking of the Pectic Polysaccharide Rhamnogalacturonan II.

The walls of suspension-cultured Chenopodium album L. cells grown continually for more than 1 year on B-deficient medium contained monomeric rhamnogalacturonan II (mRG-II) but not the borate ester cross-linked RG II dimer (dRG-II-B). The walls of these cells had an increased size limit for dextran permeation, which is a measure of wall pore size. Adding boric acid to growing B-deficient cells resulted in B binding to the wall, the formation of dRG-II-B from mRG-II, and a reduction in wall pore size within 10 min. The wall pore size of denatured B-grown cells was increased by treatment at pH </= 2.0 or by treatment with Ca(2+)-chelating agents. The acid-mediated increase in wall pore size was prevented by boric acid alone at pH 2.0 and by boric acid together with Ca(2+), but not by Na(+) or Mg(2+) ions at pH 1.5. The Ca(2+)-chelator-mediated increase in pore size was partially reduced by boric acid. Our results suggest that B-mediated cross-linking of RG-II in the walls of living plant cells generates a pectin network with a decreased size exclusion limit for polymers. The formation, stability, and possible functions of a borate ester cross-linked pectic network in the primary walls of nongraminaceous plant cells are discussed.

Journal Article↗

Ultrasonic microdissection of rat cerebellum for scanning electron microscopy.

The cerebelli of rats were initially fixed with aldehydes (modified Karnovsky's fixative; 503 mOsM/L) by cardiac perfusion. Blocks of tissue were razor-cut, usually longitudinal to folia, and immersed in the same fluid for 2-4 hours. Three separate methods of treatment followed: (1) immersion in 1% aqueous boric acid, or (2) in 2% phosphate buffered OsO4 followed by boric acid or (3) in an 8/2 mixture of boric acid and OsO4. After 18-48 hours immersion the blocks were dehydrated in ascending grades of acetone. They were then exposed to ultrasound in 100% acetone at frequencies of 80 kHz or 40 kHz for 10 to 20 minutes. Microdissection of cut surfaces (erosion) occurs after all three treatments. It is least extensive after boric acid, moderate after OsO4 and greatest after the combined mixture. All cerebellar cell types are recognizable as are numerous fibers according to morphology and position. Variable erosion accommodates analysis of different levels of neural organization. In general, structural situations not involving great depth of field are best revealed by H3BO3 or OsO4. Blood vascular relationships to other structures are best demonstrated in deeply eroded specimens.

Animals↗

Boron modulates extracellular matrix and TNF alpha synthesis in human fibroblasts.

Boric acid was not mitogenic for human fibroblasts and it did not change cell viability until 0.5% (w/v). Boric acid treatment affected the metabolism of human dermal fibroblasts in culture, decreasing the synthesis of extracellular matrix macromolecules such as proteoglycans, collagen, and total proteins. It also increased the release of these molecules into the culture medium. The principal proteins secreted into the medium after boric acid treatment had molecular masses of 90, 70, 58, 49, and 43 kDa and faint bands were detected by electrophoresis between 14 and 30 kDa. hsp 70 and TNF alpha were detected among the secreted proteins by immunoblotting, and the amount of TNF alpha released was quantified by radioimmunoassay. Total mRNA levels were higher after boric acid treatment and peaked after 6 h of treatment. TNF alpha mRNA was undetectable in unstimulated fibroblasts and two TNF alpha mRNA bands were detected after stimulation: immature mRNA (4.8 kb) and mature TNF alpha mRNA (1.9 kb). Thus, the effects of boric acid observed in wound repair in vivo may be due to TNF alpha synthesis and secretion.

Boric Acids↗

The boron requirement and cell wall properties of growing and stationary suspension-cultured chenopodium album L. cells

Suspension-cultured Chenopodium album L. cells are capable of continuous, long-term growth on a boron-deficient medium. Compared with cultures grown with boron, these cultures contained more enlarged and detached cells, had increased turbidity due to the rupture of a small number of cells, and contained cells with an increased cell wall pore size. These characteristics were reversed by the addition of boric acid (>/=7 &mgr;M) to the boron-deficient cells. C. album cells grown in the presence of 100 &mgr;M boric acid entered the stationary phase when they were not subcultured, and remained viable for at least 3 weeks. The transition from the growth phase to the stationary phase was accompanied by a decrease in the wall pore size. Cells grown without boric acid or with 7 &mgr;M boric acid were not able to reduce their wall pore size at the transition to the stationary phase. These cells could not be kept viable in the stationary phase, because they continued to expand and died as a result of wall rupture. The addition of 100 &mgr;M boric acid prevented wall rupture and the wall pore size was reduced to normal values. We conclude that boron is required to maintain the normal pore structure of the wall matrix and to mechanically stabilize the wall at growth termination.

Journal Article↗

Comparative toxicology of borates.

Inorganic borates, including boric acid, Na, ammonium, K, and Zn borates generally display low acute toxicity orally, dermally, and by inhalation. They are either not irritant or mild skin and eye irritants. Exceptions owing to physiochemical properties do occur. Longer-term toxicological studies have been reported mainly on boric acid or borax where the properties are generally similar on an equivalent boron (B) basis. The critical effects in several species are male reproductive toxicity and developmental toxicity. The doses that cause these effects are far higher than any levels to which the human population could be exposed. Humans would need to consume daily some 3.3 g of boric acid (or 5.0 g borax) to ingest the same dose level as the lowest animal NOAEL. No effects on fertility were seen in a population of workers exposed to borates or to a population exposed to high environmental borate levels. There is remarkable similarity in the toxicological effects of boric acid and borax across different species. Other inorganic borates that simply dissociate to boric acid are expected to display similar toxicity, whereas those that do not dissociate simply to boric acid may display a different toxicological profile.

Animals↗

Laboratory and field performance of consumer bait products for German cockroach (Dictyoptera: Blattellidae) control.

Bait formulations containing boric acid, chlorpyrifos, or hydramethylnon were evaluated in field and laboratory experiments against the German cockroach, Blattella germanica (L.). In continuous exposure tests, chlorpyrifos formulations produced 100% mortality in less than 24 h, boric acid formulations had LT50's of approximately 5.5 d, and hydramethylnon had an LT50 of 0.86 d. LT50's estimated in Ebeling choice boxes were 1.6 to 10.8 times greater than those from continuous exposure tests for chlorpyrifos formulations and 2.5 times greater for the hydramethylnon formulation. The same LT50's were produced by choice box and continuous exposure tests for boric acid formulations. Relative repellency, measured as the mean percentage of live cockroaches in the light side of the choice box, was greatest for chlorpyrifos formulations, followed by boric acid formulations, then hydramethylnon. A performance index (PI) that combined choice box repellency and mortality data indicated that hydramethylnon (Combat) had the greatest potential for field effectiveness. Only hydramethylnon significantly reduced German cockroach populations in the field. Apartments treated with the IT WORKS formulation of boric acid bait had significantly greater cockroach trap catches. The PI is an accurate predictor of the field performance of toxic baits for German cockroach control.

Animals↗

Topical quinolone vs. antiseptic for treating chronic suppurative otitis media: a randomized controlled trial.

OBJECTIVE: To compare a topical quinolone antibiotic (ciprofloxacin) with a cheaper topical antiseptic (boric acid) for treating chronic suppurative otitis media in children. DESIGN: Randomized controlled trial. SETTING AND PARTICIPANTS: A total of 427 children with chronic suppurative otitis media enrolled from 141 schools following screening of 39 841 schoolchildren in Kenya. Intervention Topical ciprofloxacin (n = 216) or boric acid in alcohol (n = 211); child-to-child treatment twice daily for 2 weeks. MAIN OUTCOME MEASURES: Resolution of discharge (at 2 weeks for primary outcome), healing of the tympanic membrane, and change in hearing threshold from baseline, all at 2 and 4 weeks. RESULTS: At 2 weeks, discharge was resolved in 123 of 207 (59%) children given ciprofloxacin, and in 65 of 204 (32%) given boric acid (relative risk 1.86; 95% CI 1.48-2.35; P < 0.0001). This effect was also significant at 4 weeks, and ciprofloxacin was associated with better hearing at both visits. No difference with respect to tympanic membrane healing was detected. There were significantly fewer adverse events of ear pain, irritation, and bleeding on mopping with ciprofloxacin than boric acid. CONCLUSIONS: Ciprofloxacin performed better than boric acid and alcohol for treating chronic suppurative otitis media in children in Kenya.

Adolescent↗

Oral toxicity and repellency of borates to German cockroaches (Dictyoptera: Blattellidae).

The oral toxicities of boric acid and disodium octaborate tetrahydrate (DSOBTH) in dry-mixed, wet-mixed, and water-based solution baits were determined for German cockroaches, Blattella germanica L., in choice and nonchoice experiments. In dry-mixed, nonchoice bait tests, all cockroaches died within 1 wk. Time to mortality decreased as the concentration of boric acid increased. The LT50s for DSOBTH were not significantly different for any concentrations tested. In choice tests, the order of LT50s of boric acid and DSOBTH were 6.25% = 12.5% > 25% = 50% and 25% > 12.5% > 50% > 25%, respectively. Consumption of treated and control baits and the differences between the LT50s of the nonchoice and choice tests indicate repellency of the toxicants. Most German cockroaches died in 3-6 d in wet-mixed nonchoice tests, but all cockroaches survived the wet-mixed choice tests except at the lowest concentration of boric acid. This result indicated repellency. In nonchoice tests with water-based solutions, all cockroaches died in 5 d. In choice tests with boric acid solutions, mortality did not increase at concentrations > 1%. Choice/nonchoice ratios indicate no repellency of water-based solutions. In addition, consumption of treated and blank solutions was not significantly different for any concentration except 4% DSOBTH.

Administration, Oral↗

Chemical disposition of boron in animals and humans.

Elemental boron was isolated in 1808. It typically occurs in nature as borates hydrated with varying amounts of water. Important compounds are boric acid and borax. Boron compounds are also used in the production of metals, enamels, and glasses. In trace amounts, boron is essential for the growth of many plants, and is found in animal and human tissues at low concentrations. Poisoning in humans has been reported as the result of accidental ingestion or use of large amounts in the treatment of burns. Boron as boric acid is fairly rapidly absorbed and excreted from the body via urine. The half-life of boric acid in humans is on the order of 1 day. Boron does not appear to accumulate in soft tissues of animals, but does accumulate in bone. Normal levels of boron in soft tissues, urine, and blood generally range from less than 0.05 ppm to no more than 10 ppm. In poisoning incidents, the amount of boric acid in brain and liver tissue has been reported to be as high as 2000 ppm. Recent studies at the National Institute of Environmental Health Sciences have indicated that boron may contribute to reduced fertility in male rodents fed 9000 ppm of boric acid in feed. Within a few days, boron levels in blood and most soft tissues quickly reached a plateau of about 15 ppm. Boron in bone did not appear to plateau, reaching 47 ppm after 7 days on the diet. Cessation of exposure to dietary boron resulted in a rapid drop in bone boron.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Tissue disposition of boron in male Fischer rats.

Boric acid (H3BO3), an inorganic acid with widespread commercial use and consumer exposure, impairs fertility in male rodents at dose levels lower than those required to cause other adverse effects. Previous studies found a testicular lesion in adult Fischer rats fed 9000 ppm boric acid (1575 ppm boron) and slightly reduced basal serum testosterone levels. A CNS-mediated hormonal component to this lesion was suggested. Detailed data on the tissue disposition of boron in the rat, including accessory sex organs and the brain, are lacking. This study examined the tissue disposition of boron in reproductive, accessory sex organs, and other selected tissues in adult male Fischer rats fed 9000 ppm boric acid to determine if selective accumulation of boron in reproductive tissues, accessory sex organs, and/or the brain might correlate with and explain the apparent selective testicular toxicity. Adult male Fischer rats were fed 9000 ppm boric acid for up to 7 days. Animals were killed at 1, 2, 3, 4, and 7 days after the start of exposure. Plasma and excised tissues were heat-digested in acid and analyzed for boron by inductively coupled argon plasma emission spectrometry (ICAP). With the exception of adrenal glands, control boron levels in all tissues examined were below 4 micrograms/g. There was a rapid increase in plasma and tissue boron 1 day after the start of exposure (range 2- to 20-fold), with the exception of adipose tissue. With the exception of bone and adipose tissue, all soft tissues examined, including the testis, epididymis, accessory sex organs, hypothalamus, and rest of brain, appeared to reach steady-state boron levels (range 12-30 micrograms/g) by 3-4 days. Bone boron levels continued to increase up to the termination at 7 days (40-50 micrograms/g by Day 7). Bone attained the greatest concentration of boron (2- to 3-fold over plasma levels) while levels in adipose tissue were 20% of plasma levels during the 7-day exposure period. All other tissues appeared to show no appreciable accumulation of boron over plasma levels. The data suggest that neither the apparent selective testicular toxicity nor the slight CNS hormonal effect associated with boric acid exposure can be explained on the basis of selective accumulation of boron in the testis or brain/hypothalamus, respectively. Thus, the testicular toxicity is likely the result of certain biological processes that are unique to the testis and which are targets of boron exposure.

Animals↗

[Special characteristics of topical treatment in childhood].

Although the barrier function and thickness of the stratum corneum is fully developed in newborns, the infant shows numerous differences in cutaneous and systemic metabolism of topically applied substances in comparison to adults. This discrepancy between children and adults has been explained by the greater systemic availability due to the greater surface area to weight ratio in children. Several topically applied drugs such as hexachlorophene, phenol, salicylic acid and boric acid in high concentration or on large areas have caused toxic reactions and fatalities in infants. Therapeutic approaches to childhood dermatoses differ from these used in adults. These age-dependent differences concerning the topical application of glucocorticosteroids, urea and dyes are described for the treatment of atopic eczema. The development of innovative topical drugs may extend therapeutic options especially in children as shown by a new topical anesthetic cream improving the treatment of mollusca contagiosa, a common childhood problem. Finally, certain physiological differences should be considered in newborn and infant skin care.

Administration, Topical↗

Preparation and structural characterization of three types of homo- and heterotrinuclear boron complexes: salen[[B-O-B][O2BOH]], salen[[B-O-B][O2BPh]], and salen[[B-O-B][O2P(O)Ph]].

Three types of homo- and heterotrinuclear boron complexes have been obtained in moderate to good yields from reactions of salen-type ligands with boric acid and combinations of boric acid with phenylboronic and phenylphosphonic acid. The products are air-stable and have relatively high melting points (>290 degrees C) but are poorly soluble or insoluble in common organic solvents. They have been characterized as far as possible by elemental analysis, mass spectrometry, IR, (1)H, (11)B, and (31)P NMR spectroscopy, and X-ray crystallography. Furthermore, theoretical calculations have been performed for representative examples to permit a complete comparison of the different structure types. A detailed analysis of the molecular structures showed that the complexes are constructed around a central B(3)O(3) or B(2)PO(3) ring. The salen ligands are attached to two boron atoms of these rings, which have therefore tetrahedral coordination geometries. The complexes contain seven- and eight-membered heterocycles of the B(2)C(n)ON(2) (n = 2, 3) type with chair or twisted-chair and boat-chair or chair-chair conformations, respectively. In the homotrinuclear complexes one of the three boron atoms is three-coordinate and can therefore still act as Lewis acid, thus making these products interesting for catalytic applications, e.g. in asymmetric synthesis. Depending on the substitutents attached to the boron atoms, these complexes show a relationship with either trimetaboric acid, boroxine, or the tetraborate dianion found in Borax.

Journal Article↗

[Effect of seed soaking in plant hormone and trace element fertilizer on the growth of Psoralea corylifolia L].

Our study shows that seed soaking in triacontanol, ammonium molybdate and gibberellin can promote the growth of P. corylifolia, reduce its premature flower and fruit drop, raise the fruit-bearing rate by 6.5-17.4%, and fruit-bearing number by 21.6-28.4%, so as to increase the yield per unit area by 31.5-34.8%. Seed soaking in naphthylacetic acid and boric acid does not give such a marked effect.

Fabaceae↗

[Clinical aspects, epidemiology and economic impact of foot epidermomycosis in an industrial milieu].

Fungal infections of the feet are very common in some professions. This has been particularly studied in coal mine workers up to 50 p. 100 of whom were found to have dermatophytosis of the feet. The purpose of this study was to determine the clinical, epidemiological and evolutive characteristics of interdigital and plantar intertrigo of the feet among people working in a coking plant, a potash mine and a motorcar factory. We have also evaluated the cost of treatments in relation to their immediate effectiveness and their preventive effects on relapses. Initially, 208 workers entered the study: 84 (40.7 p. 100) had a mycotic infection (M) and 124 (59.3 p. 100) presented with a non-mycotic (NM) inflammation between the toes and on the soles, characterized by maceration of the skin, hyperhidrosis and bromhidrosis. Change in the lesions under treatment were subjected to statistical analysis. In both M and NM groups the workers were allocated by randomization to a double-blind treatment consisting of: group M: either 2 p. 100 miconazole powder or talcum powder with 2 p. 100 salicylic acid and boric acid; group NM: either 2 p. 100 miconazole powder or ordinary talcum powder. Each subject was seen on at least two occasions after 3 and 12 months of daily foot care and topical treatment. Mycological examinations in group M subjects showed that fungal infections of the feet were primarily due to Trichophyton mentagrophytes or to Trichophyton rubrum. A logistic regression analysis (BMDPLR program) of anamnestic and clinical data (table IV) led to a "mathematical model of the mycotic foot", characterized by 6 main parameters of statistically significant occurrence: a history of interdigital-plantar intertrigo, recurrent in 90 p. 100 of subjects in group M (significant association at 0.1 p. 100); a functional symptom, pruritus, present in 71 p. 100 of subjects with mycosis; the stronger, more disturbing the pruritus, the greater the probability of it being of fungal origin (significant association at 0.1 p. 100); 4 physical signs: lack of maceration (0.1 p. 100), lesions limited to the interdigital spaces and respecting the soles (0.1 p. 100), presence of interdigital fissures (0.5 p. 100) and vesiculation (2.5 p. 100). When the respective diagnostic values of these elementary symptoms were considered, it appeared that their various combinations might have predictive values which could be calculated.(ABSTRACT TRUNCATED AT 400 WORDS)

Computer Simulation↗

Measurement of borate in occupational environments.

The hydration stability for inhalable borate particles has been characterized as a function of temperature and relative humidity when collected by a field personnel monitor. The rate of hydration was measured for boric acid (B[OH]3); Neobor borax 5 mol (Na2O x 2B2O3 x 5H2O); borax 10 mol (Na2O x 2B2O3 x 10H2O); anhydrous boric acid (B2O3); and anhydrous borax (Na2O x 2B2O3). The particle size is large in bulk commercial products, such that they can be handled and stored without problems. However, inhalable dust particles, in the range of 20 microm (MMD), undergo hydration/dehydration rapidly owing to their high surface-to-volume ratio. The hydration state of a collected air sample was found to be strongly dependent on the conditions of relative humidity and temperature during its collection. As a consequence, the actual chemical species of dust being inspired cannot be identified accurately. Inhalable particles of borax 10 mol placed in a field personal monitoring cartridge and exposed to dry air at 2.0 L/min at 70 degrees F for 7 h undergo rapid dehydration, producing a sodium borate residue having significantly less than four waters of hydration. Likewise, inhalable particles of anhydrous boric acid and anhydrous borax were found to hydrate under normal atmospheric conditions. Borax 5 mol and boric acid were found to be stable to dehydration. In most cases, the specific borate species or borate compounds collected in a field monitor cannot be accurately characterized other than by their boron (B) content.

Borates↗