Biomedical subjects

P Strong

Publications and source records attributed to P Strong.

At least 19 recordsLinked to original sources

PubMed2006

Treatment with chitin microparticles is protective against lung histopathology in a murine asthma model.

BACKGROUND: Chitin, a natural polysaccharide extracted from shrimp, is a potent T and B cell adjuvant when delivered in the form of chitin microparticles and can shift a polarized T-helper type 2 (Th2) immune response towards a Th1 response. OBJECTIVE: We investigated the beneficial effects of the intranasal application of chitin microparticles in newborn mice before and after the establishment of a model of allergic asthma. METHODS: Mice were grouped as asthma (A), primary prevention (PP), treatment (T), primary prevention+treatment (PPT) and control (C) groups. All mice except controls were sensitized with ovalbumin intraperitoneally and challenged intratracheally to establish the asthma model. Mice in the PP and PPT groups received chitin microparticles intranasally during the newborn period before sensitization. Mice in the PPT and T groups received intranasal chitin microparticles after challenge. Airway histopathology was evaluated in all groups. RESULTS: All of the airway histopathologic parameters of small and medium-sized airways of the T and PPT groups were significantly ameliorated when compared with the asthma model group. In the large airways, thicknesses of basement membrane, epithelium and subepithelial smooth muscle layers of the PPT group and basement membrane thicknesses of the T group were also significantly lower compared with the asthma model group. Comparison of the PP group with the asthma model group revealed significantly reduced goblet cell numbers and significantly reduced epithelial and basement membrane thicknesses in small and medium airways, in addition to significantly reduced basement membrane thicknesses in the medium-sized airways. CONCLUSION: Intranasal application of microgram quantities of chitin microparticles had a beneficial effect in preventing and treating histopathologic changes in the airways of asthmatic mice.

Administration, Intranasal↗

PubMed2004

Airway inflammation in children with tracheostomy.

We hypothesised that long-term tracheostomy in infants and children may perpetuate chronic airway inflammation and airway remodeling due to easier access to the lungs for microorganisms. Pulmonary surfactant represents an important part of the initial host defense, and in particular, the surfactant proteins (SP) A and D may directly interact with invading microorganisms and also modulate the activity of local immune cells. The goals of this study were to determine the presence and intensity of a peripheral airway inflammation and of potential deficiency states of surfactant proteins in nonsymptomatic children with tracheostomy. Bronchoalveolar lavage (BAL) cell pattern, bacteria and viruses recovered, and concentrations of SP-A, SP-B, SP-C, and SP-D were assessed in 46 children (4.3 years (1.6-6)) median (range) carrying a tracheostomy for 2.4 years (1.3-4.9), and were compared to 16 children with no lung disease. Children with tracheostomy had an increased total number of cells, increased neutrophils, and more frequently bacteria, but no viruses were recovered. SP-D concentration was reduced by 50% on average (P = 0.0002). SP-A, SP-B, and SP-C were not different between the two groups. SP-D was inversely correlated to neutrophils, and high numbers of bacteria were associated with lower SP-D concentrations. We suggest that bacteria and low SP-D support neutrophilic inflammation in the lower respiratory tract of nonsymptomatic with children with tracheostomy.

Bronchoalveolar Lavage↗

PubMed2003

A recombinant fragment of human SP-D reduces allergic responses in mice sensitized to house dust mite allergens.

C57Bl6 mice sensitized to Dermatophagoides pteronyssinus and challenged with D. pteronyssinus allergen extract given intranasally followed by treatment with intranasal applications of a 60-kDa truncated, trimeric recombinant form of human SP-D (rfhSP-D) showed a significant reduction in serum IgE, IgG1, peripheral blood eosinophilia and airway hyperresponsiveness compared to saline or bovine serum albumin-treated controls. Intracellular cytokine staining of lung and spleen homogenates showed increases in interleukin (IL)-12 production in lung tissue and normalization of IL-12 and interferon (IFN)-gamma in spleen tissue. In previous studies we demonstrated the effectiveness of native SP-D and rfhSP-D in down-regulating allergic responses to allergens of Aspergillus fumigatus. The results reported here indicate that rfhSP-D can suppress the development of allergic symptoms in sensitized mice challenged with allergens of the common house dust mite.

Animals↗

PubMed2002

Intranasal application of chitin microparticles down-regulates symptoms of allergic hypersensitivity to Dermatophagoides pteronyssinus and Aspergillus fumigatus in murine models of allergy.

BACKGROUND: Previous studies have demonstrated that chitin in the form of microparticles that can be phagocytosed is a potent macrophage stimulator and promotes a Th1 cytokine response and it has been shown that oral administration of chitin microparticles is effective in down-regulating serum IgE and lung eosinophilia in a mouse model of ragweed allergy. To date there have been no studies on the effectivness of directly applying chitin microparticles to the respiratory tract as a treatment for allergic symptoms. OBJECTIVE: To test the effectivness of chitin microparticles when given intranasally as a treatment for the symptoms of respiratory allergy and allergic asthma and to compare its effectivness in two different mouse models of allergy, namely to Dermatophagoides pteronyssinus and Aspergilhus fumigatus. RESULTS: The intranasal application of microgram doses of chitin microparticles is an effective treatment for reducing serum IgE and peripheral blood eosinophilia, airway hyper-responsiveness and lung inflammation in both allergy models results in elevation in Th1 cytokines IL-12, IFN-gamma and TNF-alpha and reduction in IL-4 production during allergen challenge. CONCLUSION: Chitin microparticle suspensions have Th1 immunostimulatory properties and are effective when administered intranasally in mice. The stimulation of the nasal associated lymphoid tissue with chitin microparticles could offer a novel and natural approach to treating allergic disease in humans.

Administration, Intranasal↗

PubMed2002

Intranasal delivery of a truncated recombinant human SP-D is effective at down-regulating allergic hypersensitivity in mice sensitized to allergens of Aspergillus fumigatus.

C57BL/6 mice were sensitized to Aspergillus fumigatus 1-week culture filtrate, which is rich in the non-glycosylated allergen Asp f1, a major allergen in allergic bronchopulmonary aspergillosis (ABPA). A comparison of the effect of treatment of allergen challenged mice by intranasal administration of a 60-kDa truncated recombinant form of human SP-D (rfhSP-D) or recombinant full length SP-A (rhSP-A) was undertaken. Treatment with rfhSP-D produced significant reduction in IgE, IgG1 and peripheral blood eosinophilia and treatment with rfhSP-D, but not rhSP-A resulted in a significant reduction in airway hyperresponsiveness as measured by whole body plethysmography. Lung histology revealed less peribronchial lymphocytic infiltration in mice treated with rfhSP-D. Intracellular cytokine staining of spleen homogenates showed increases in IL-12 and IFN-gamma and decrease in IL-4. The level of endogenous mouse SP-D was elevated sixfold in the lungs of sensitized mice and was not affected by treatment with rfhSP-D. Taken with our previous studies, with a BALB/c mouse model of ABPA using a 3-week A. fumigatus culture filtrate, the present results show that rfhSP-D can suppress the development of allergic symptoms in sensitized mice independent of genetic background and using a different preparation of A. fumigatus allergens.

Administration, Intranasal↗

PubMed2001

A recombinant homotrimer, composed of the alpha helical neck region of human surfactant protein D and C1q B chain globular domain, is an inhibitor of the classical complement pathway.

The first step in the activation of the classical complement pathway by immune complexes involves the binding of the six globular heads of C1q to the Fc regions of IgG or IgM. The globular heads of C1q (gC1q domain) are located C-terminal to the six triple-helical stalks present in the molecule, each head being composed of the C-terminal halves of one A, one B, and one C chain. The gC1q modules are also found in a variety of noncomplement proteins, such as type VIII and X collagens, precerebellin, hibernation protein, multimerin, Acrp-30, and saccular collagen. In several of these proteins, the chains containing these gC1q modules appear to form a homotrimeric structure. Here, we report expression of an in-frame fusion of a trimerizing neck region of surfactant protein D with the globular head region of C1q B chain as a fusion to Escherichia coli maltose binding protein. Following cleavage by factor Xa and removal of the maltose binding protein, the neck and globular region, designated ghB(3), formed a soluble, homotrimeric structure and could inhibit C1q-dependent hemolysis of IgG- and IgM-sensitized sheep erythrocytes. The functional properties of ghB(3) indicate that the globular regions of C1q may adopt a modular organization in which each globular head of C1q may be composed of three structurally and functionally independent domains, thus retaining multivalency in the form of a heterotrimer. The finding that ghB(3) is an inhibitor of C1q-mediated complement activation opens up the possibility of blocking activation at the first step of the classical complement pathway.

Animals↗

PubMed2001

Protective role of lung surfactant protein D in a murine model of invasive pulmonary aspergillosis.

The protective effects of intranasal administration of amphotericin B (AmB), human SP-A, SP-D and a 60-kDa fragment of SP-D (rSP-D) were examined in a murine model of invasive pulmonary aspergillosis (IPA). The untreated group of IPA mice showed no survival at 7 days postinfection. Treatment with AmB, SP-D, and rSP-D increased the survival rate to 80, 60, and 80%, respectively, suggesting that SP-D (and rSP-D) can protect immunosuppressed mice from an otherwise fatal challenge with Aspergillus fumigatus conidia.

Amphotericin B↗

PubMed2001

Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens.

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic disorder caused by an opportunistic fungal pathogen, Aspergillus fumigatus (AFU:). Lung surfactant proteins SP-A and SP-D can interact with the glycosylated antigens and allergens of AFU:, inhibit specific IgE binding to these allergens, and block histamine release from sensitized basophils. We have now examined the therapeutic effect of exogenous administration of human SP-A, SP-D, and a recombinant fragment of SP-D (rSP-D), in a murine model of pulmonary hypersensitivity induced by AFU: antigens and allergens, which resembles human ABPA immunologically. The ABPA mice exhibited high levels of AFU:-specific IgG and IgE, blood eosinophilia, extensive infiltration of lymphocytes and eosinophils in the lung sections, and a Th2 cytokine response. Treatment with SP-A, SP-D, and rSP-D lowered blood eosinophilia, pulmonary infiltration, and specific Ab levels considerably, which persisted up to 4 days in the SP-A-treated ABPA mice, and up to 16 days in the SP-D- or rSP-D-treated ABPA mice. The levels of IL-2, IL-4, and IL-5 were decreased, while the level of IFN-gamma was raised in the splenic supernatants of the treated mice, indicating a marked shift from Th2 to Th1 response. These results clearly implicate pulmonary SP-A and SP-D in the modulation of allergic reactions.

Allergens↗

PubMed2000

Massive idiosyncratic exon skipping corrects the nonsense mutation in dystrophic mouse muscle and produces functional revertant fibers by clonal expansion.

Conventionally, nonsense mutations within a gene preclude synthesis of a full-length functional protein. Obviation of such a blockage is seen in the mdx mouse, where despite a nonsense mutation in exon 23 of the dystrophin gene, occasional so-called revertant muscle fibers are seen to contain near-normal levels of its protein product. Here, we show that reversion of dystrophin expression in mdx mice muscle involves unprecedented massive loss of up to 30 exons. We detected several alternatively processed transcripts that could account for some of the revertant dystrophins and could not detect genomic deletion from the region commonly skipped in revertant dystrophin. This, together with exon skipping in two noncontiguous regions, favors aberrant splicing as the mechanism for the restoration of dystrophin, but is hard to reconcile with the clonal idiosyncrasy of revertant dystrophins. Revertant dystrophins retain functional domains and mediate plasmalemmal assembly of the dystrophin-associated glycoprotein complex. Physiological function of revertant fibers is demonstrated by the clonal growth of revertant clusters with age, suggesting that revertant dystrophin could be used as a guide to the construction of dystrophin expression vectors for individual gene therapy. The dystrophin gene in the mdx mouse provides a favored system for study of exon skipping associated with nonsense mutations.

Aging↗

PubMed2000

Altered airway surfactant phospholipid composition and reduced lung function in asthma.

Pulmonary surfactant in bronchoalveolar lavage fluid (BALF) and induced sputum from adults with stable asthma (n = 36) and healthy controls (n = 12) was analyzed for phospholipid and protein compositions and function. Asthmatic subjects were graded as mild, moderate, or severe. Phospholipid compositions of BALF and sputum from control subjects were similar and characteristic of surfactant. For asthmatic subjects, the proportion of dipalmitoyl phosphatidylcholine (16:0/16:0PC), the major phospholipid in surfactant, decreased in sputum (P < 0.05) but not in BALF. In BALF, mole percent 16:0/16:0PC correlated with surfactant function measured in a capillary surfactometer, and sputum mole percent 16:0/16:0PC correlated with lung function (forced expiratory volume in 1 s). Neither surfactant protein A nor total protein concentration in either BALF or sputum was altered in asthma. These results suggest altered phospholipid composition and function of airway (sputum) but not alveolar (BALF) surfactant in stable asthma. Such underlying surfactant dysfunction may predispose asthmatic subjects to further surfactant inhibition by proteins or aeroallergens in acute asthma episodes and contribute to airway closure in asthma. Consequently, administration of an appropriate therapeutic surfactant could provide clinical benefit in asthma.

Adolescent↗

PubMed1999

Enhanced expression of recombinant dystrophin following intramuscular injection of Epstein-Barr virus (EBV)-based mini-chromosome vectors in mdx mice.

Gene transfer by direct intramuscular injection of naked plasmid DNA has been shown to be a safe, simple but relatively inefficient method for gene delivery in vivo. Eukaryotic plasmid expression vectors incorporating the Epstein-Barr virus (EBV) origin of replication (oriP) and EBNA1 gene have been shown to act as autonomous episomally replicating gene transfer vectors which additionally provide nuclear matrix retention functions. Prolonged expression of a LacZ reporter gene and recombinant human dystrophin was shown using EBV-based plasmid vectors transfected into C2C12 mouse myoblast and myotube cultures. Intramuscular injection of EBV-based dystrophin expression plasmids into nude/mdx mice resulted in significant enhancement in the number of muscle fibres expressing recombinant dystrophin compared with a conventional vector. This effect was observed for over 10 weeks after a single administration. These results indicate the potential advantage of EBV-based expression vectors for focal plasmid-mediated gene augmentation therapy in Duchenne muscular dystrophy (DMD) and a range of other gene therapeutic applications.

Animals↗

PubMed1998

Evidence that C1q binds specifically to CH2-like immunoglobulin gamma motifs present in the autoantigen calreticulin and interferes with complement activation.

Calreticulin (CRT) is located predominantly in the endoplasmic reticulum (ER) of cells, where it functions as a quality control controller of protein folding. However, CRT is also a prevalent autoantigen in patients with systemic lupus erythematosus (SLE), where its release from the cell may arise as a results of dysfunctional apoptosis and inefficient removal of ER vesicles, which are an abundant source of CRT and other autoantigens. Indicative of this is the presence of autoantibodies against CRT in the sera of 40-60% of all SLE patients. Once released into the circulation, CRT might bind directly to C1q and we have suggested that this association may result in a defect in C1q-mediated clearance of antigen-antibody complexes. It has been previously shown that CRT under physiological salt conditions binds to the globular head of C1q. It is known that the globular head region of C1q binds to the CH2 domain in the Fc portion of immunoglobulin gamma (IgG). The N-terminal half of CRT contains a number of short regions of 7-10 amino acids that show sequence similarity to the putative C1q binding region in the CH2 domain of IgG. By use of a series of 92 overlapping CRT synthetic peptides, a number of C1q binding sites on the CRT molecule have been identified, including several containing a CH2-like motif similar to the ExKxKx C1q binding motif found in the CH2 domain of IgG. A number of these peptides were shown to inhibit binding of C1q to IgG and reduce binding of native CRT to C1q. Moreover, several of the peptides were capable of inhibiting the classical pathway of complement activation. These studies have identified specific binding sites on the CRT molecule for C1q and lend support to the hypothesis that interaction of CRT with C1q may interfere with the ability of C1q to associate with immune complexes in autoimmune-related disorders.

Amino Acid Sequence↗

PubMed1998

A novel method of purifying lung surfactant proteins A and D from the lung lavage of alveolar proteinosis patients and from pooled amniotic fluid.

A simple procedure has been developed for the purification of the surfactant proteins SP-A and SP-D from lung lavage of patients with alveolar proteinosis. The SP-D is purified by fractionation of the supernatant obtained after spinning the lavage at 10000 X g for 40 min, while the bulk of the SP-A is purified by fractionation of the pellet. The supernatant is applied to a maltosyl-agarose column and the bound SP-D is specifically eluted using MnCl2. The pellet is solubilised in 6 M urea and, following renaturation, the solubilised proteins are applied to maltosyl-agarose and SP-A eluted using a gradient of EDTA. Both SP-A and SP-D are further purified by gel-filtration on Superose-6. This procedure has also been used to prepare successfully human SP-A and SP-D from amniotic fluid and may be generally applicable to the isolation of these surfactant proteins from lung washings obtained from other species.

Amniotic Fluid↗

PubMed1998

Functional characterization of a recombinant form of the C-terminal, globular head region of the B-chain of human serum complement protein, C1q.

The first step in the activation of the classical pathway of the complement system by immune complexes involves the binding of the six globular heads of C1q to the Fc regions of IgG or IgM. The globular heads of C1q are located C-terminal to the six triple-helical stalks present in the molecule; each head is considered to be composed of the C-terminal halves (3x136 residues) of one A-, one B- and one C-chain. It is not known if the C-terminal globular regions, present in each of the three types of chain, are independently folded modules (with each chain having distinct binding properties towards immunoglobulins) or whether the different binding functions of C1q are dependent upon a globular structure which relies on contributions from all three chains. As a first step towards addressing this question, we have expressed the globular head region (residues 87-226) of the C1q B-chain (ghB) as a soluble fusion protein with maltose-binding protein (MBP) in Escherichia coli. The affinity purified fusion protein, designated MBP-ghB, behaved as a dimer on gel filtration and bound preferentially to aggregated IgG rather than to IgM. It could also inhibit C1q-dependent haemolysis of both IgG- and IgM-sensitized erythrocytes. After its release from MBP, by use of Factor Xa, the free ghB exhibited a tendency to aggregate and come out of solution. Since MBP is known to be a monomeric molecule, the dimerization of the MBP-ghB fusion polypeptide is probably brought about by the ghB region, perhaps through hydrophobic interactions within the ghB region. The functional behaviour of MBP-ghB indicates that the globular regions of C1q may adopt a modular organization, i.e. each globular head of C1q may be composed of three structurally and functionally independent domains, thus retaining multivalency in the form of a heterotrimer.

ATP-Binding Cassette Transporters↗

PubMed1998

C1q-mediated chemotaxis by human neutrophils: involvement of gClqR and G-protein signalling mechanisms.

C1q, the first component of the classical pathway of the complement system, interacts with various cell types and triggers a variety of cell-specific cellular responses, such as oxidative burst, chemotaxis, phagocytosis, etc. Different biological responses are attributed to the interaction of C1q with more than one putative cell-surface C1q receptor/C1q-binding protein. Previously, it has been shown that C1q-mediated oxidative burst by neutrophils is not linked to G-protein-coupled fMet-Leu-Phe-mediated response. In the present study, we have investigated neutrophil migration brought about by C1q and tried to identify the signal-transduction pathways involved in the chemotactic response. We found that C1q stimulated neutrophil migration in a dose-dependent manner, primarily by enhancing chemotaxis (directed movement) rather than chemokinesis (random movement). This C1q-induced chemotaxis could be abolished by an inhibitor of G-proteins (pertussis toxin) and PtdIns(3,4,5)P3 kinase (wortmannin and LY294002). The collagen tail of C1q appeared to mediate chemotaxis. gC1qR, a C1q-binding protein, has recently been reported to participate in C1q-mediated chemotaxis of murine mast cells and human eosinophils. We observed that gC1qR enhanced binding of free C1q to adherent neutrophils and promoted C1q-mediated chemotaxis of neutrophils by nearly seven-fold. Our results suggests C1q-mediated chemotaxis involves gC1qR as well as G-protein-coupled signal-transduction mechanisms operating downstream to neutrophil chemotaxis.

Androstadienes↗

PubMed1998

In vivo percutaneous absorption of boric acid, borax, and disodium octaborate tetrahydrate in humans compared to in vitro absorption in human skin from infinite and finite doses.

Literature from the first half of this century report concern for toxicity from topical use of boric acid, but assessment of percutaneous absorption has been impaired by lack of analytical sensitivity. Analytical methods in this study included inductively coupled plasma-mass spectrometry which now allows quantitation of percutaneous absorption of 10B in 10B-enriched boric acid, borax, and disodium octaborate tetrahydrate (DOT) in biological matrices. This made it possible, in the presence of comparatively large natural dietary boron intakes for the in vivo segment of this study, to quantify the boron passing through skin. Human volunteers were dosed with 10B-enriched boric acid, 5.0%, borax, 5.0%, or disodium octaborate tetrahydrate, 10%, in aqueous solutions. Urinalysis, for boron and changes in boron isotope ratios, was used to measure absorption. Boric acid in vivo percutaneous absorption was 0.226 (SD = 0.125) mean percentage dose, with flux and permeability constant (Kp) calculated at 0.009 microgram/cm2/h and 1.9 x 10(-7) cm/h, respectively. Borax absorption was 0.210 (SD = 0.194) mean percentage of dose, with flux and Kp calculated at 0.009 microgram/cm2/h and 1.8 x 10(-7) cm/h, respectively. DOT absorption was 0.122 (SD = 0.108) mean percentage, with flux and Kp calculated at 0.01 microgram/cm2/h and 1.0 x 10(-7) cm/h, respectively. Pretreatment with the potential skin irritant 2% sodium lauryl sulfate had no effect on boron skin absorption. In vitro human skin percentage of doses of boric acid absorbed were 1.2 for a 0.05% solution, 0.28 for a 0.5% solution, and 0.70 for a 5.0% solution. These absorption amounts translated into flux values of, respectively, 0.25, 0.58, and 14.58 micrograms/cm2/h and permeability constants (Kp) of 5.0 x 10(-4), 1.2 x 10(-4), and 2.9 x 10(-4) cm/h for the 0.05, 0.5, and 5.0% solutions. The above in vitro doses were at infinite, 1000 microliters/cm2 volume. At 2 microliters/cm2 (the in vivo dosing volume), flux decreased some 200-fold to 0.07 microgram/cm2/h and Kp of 1.4 x 10(-6) cm/h, while percentage of dose absorbed was 1.75%. Borax dosed at 5.0%/1000 microliters/cm2 had 0.41% dose absorbed, flux at 8.5 micrograms/cm2/h, and Kp was 1.7 x 10(-4) cm/h. Disodium octaborate tetrahydrate (DOT) dosed at 10%/1000 microliters/cm2 was 0.19% dose absorbed, flux at 7.9 micrograms/cm2/h, and Kp was 0.8 x 10(-4) cm/h. These in vitro results from infinite doses (1000 microliters/cm2) were 1000-fold greater than those obtained in the companion in vivo study. The results from the finite (2 microliters/cm2) dosing were closer (10-fold difference) to the in vivo results. General application of infinite dose percutaneous absorption values for risk assessment is questioned by these results. These in vivo results show that percutaneous absorption of boron, as boric acid, borax, and disodium octaborate tetrahydrate, through intact human skin, is low and is significantly less than the average daily dietary intake. This very low boron skin absorption makes it apparent that, for the borates tested, the use of gloves to prevent systemic uptake is unnecessary. These findings do not apply to abraded or otherwise damaged skin.

Adult↗

PubMed1998

In vivo percutaneous absorption of boron as boric acid, borax, and disodium octaborate tetrahydrate in humans: a summary.

Literature from the first half of this century reports concern for toxicity from topical use of boric acid, but assessment of percutaneous absorption has been impaired by lack of analytical sensitivity. Analytical methods in this study included inductively coupled plasma-mass spectrometry, which now allows quantitation of percutaneous absorption of 10B in 10B-enriched boric acid, borax, and disodium octaborate tetrahydrate (DOT) in biological matrices. This made it possible, in the presence of comparatively large natural dietary boron intakes for the in vivo segment of this study, to quantify the boron passing through skin. Human volunteers were dosed with 10B-enriched boric acid, 5.0%, borax, 5.0%, or disodium octaborate tetrahydrate, 10% in aqueous solutions. Urinalysis, for boron and changes in boron isotope ratios, was used to measure absorption. Boric acid in vivo percutaneous absorption was 0.226 (SD = 0.125) mean percent dose, with flux and permeability constant (Kp) calculated at 0.009 microg/cm2/h and 1.9 x 10(-7) cm/h, respectively. Borax absorption was 0.210 (SD = 0.194) mean percent dose, with flux and Kp calculated at 0.009 microg/cm2/h and 1.8 x 10(-7) cm/h, respectively. DOT absorption was 0.122 (SD = 0.108) mean percent, with flux and Kp calculated at 0.01 microg/cm2/h and 1.0 x 10(-7) cm/h, respectively. Pretreatment with the potential skin irritant 2% sodium lauryl sulfate had no effect on boron skin absorption. These in vivo results show that percutaneous absorption of boron, as boric acid, borax, and disodium octaborate tetrahydrate, through intact human skin is low and is significantly less than the average daily dietary intake. This very low boron skin absorption makes it apparent that, for the borates tested, the use of gloves to prevent systemic uptake is unnecessary. These findings do not apply to abraded or otherwise damaged skin.

Administration, Topical↗

PubMed1998

Determining human dietary requirements for boron.

A dietary requirement is defined as the lowest continuing intake of a nutrient that for a specified indicator of adequacy, will maintain a defined level of nutriture in an individual. An essential dietary component is one that the body cannot synthesize in sufficient quantities to maintain health. Recommended dietary allowances (RDAs) are based on estimates of the dietary requirements, and are designed to prevent deficiency diseases and promote health through an adequate diet. In 1996, the Food and Nutrition Board (FNB) began a revision process of the RDAs using as criteria specific indicators of adequacy and functional end points for reducing the risk of chronic disease. Boron (B) is a dietary component, and evidence from animal studies indicates that it is a dietary essential; it cannot be synthesized in tissues, and organisms exposed to very low levels of B show developmental defects. In humans, there is evidence of homeostatic regulation of B and an interrelationship with bone metabolism. To understand better the relationship between dietary B and B homeostasis, we measured the dietary B intake and urinary B losses in seven male participants of a controlled metabolic study of Zn homeostasis. Average dietary B intake for the repeated menu days, days 1, 2, and 3, was 4.56, 1.87, and 4.75 mg/d, respectively. Urinary B excretion during the 42-d collection period averaged 3.20 +/- 0.41 mg/d. When dietary B was low, urinary B loss (2.92 mg/d) was significantly lower than when B intake was higher (3.15 and 3.54 mg/d). Our study showed that urinary B excretion changes rapidly with changes in B intake, indicating that the kidney is the site of homeostatic regulation. To enable establishment of a dietary requirement for B in the future, further research of homeostatic regulation and functional markers of B metabolism need to be performed, followed by epidemiological studies to identify health conditions associated with inadequate dietary B.

Adult↗