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The biomimetic [Cr(3)O(O(2)CCH(2)CH(3))(6)(H(2)O)(3)](+ )decreases plasma insulin, cholesterol, and triglycerides in healthy and type II diabetic rats but not type I diabetic rats.

The in vivo effects of administration of the synthetic, functional biomimetic cation [Cr(3)O(O(2)CCH(2)CH(3))(6)(H(2)O)(3)](+) to healthy and type I and type II diabetic model rats are described. In contrast to current chromium-containing nutrition supplements, which only serve as sources of absorbable chromium, the trinuclear cation has been shown in in vitro assays to interact with the insulin receptor, activating its kinase activity, presumably by trapping the receptor in its active conformation. Thus, treatment of rats with the trinuclear cation would be expected to result in changes in lipid and carbohydrate metabolism related to insulin action. After 24 weeks of intravenous administration (0-20 micro g Cr/kg body mass), the cation results in a concentration-dependent lowering of levels of fasting blood plasma LDL cholesterol, total cholesterol, triglycerides, and insulin and of 2-h plasma insulin and glucose levels after a glucose challenge; these results confirm a previous 12-week study examining the effect of the synthetic cation on healthy rats and are in stark contrast to those of administration of other forms of Cr(III) to rats, which have no effect on these parameters. The cation has little, if any, effect on rats with STZ-induced diabetes (a type I diabetes model). However, Zucker obese rats (a model of the early stages of type II diabetes) after 24 weeks of supplementation (20 micro g/kg) have lower fasting plasma total, HDL, and LDL cholesterol, triglycerides, and insulin levels and lower 2-h plasma insulin levels. The lowering of plasma insulin concentrations with little effect on glucose concentrations suggests that the supplement increases insulin sensitivity.

Animals↗

Oral administration of the biomimetic [Cr3O(O2CCH2CH3)6(H2O)3]+ increases insulin sensitivity and improves blood plasma variables in healthy and type 2 diabetic rats.

The in vivo effects of gavage administration of the synthetic, functional biomimetic cation [Cr(3)O(O(2)CCH(2)CH(3))(6)(H(2)O)(3)](+) to healthy and type 2 diabetic model rats are described. After 24 weeks of treatment (0-1,000 microg Cr/kg body mass) of healthy Sprague Dawley rats, the cation results in a lowering (P < 0.05) of fasting blood plasma low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, and insulin levels and of 2-h plasma insulin and glucose concentrations after a glucose challenge. Zucker obese rats (a model of the early stages of type 2 diabetes) and Zucker diabetic fatty rats (a model for type 2 diabetes) after supplementation (1,000 microg Cr/kg) have lower fasting plasma total, high-density lipoprotein, and LDL cholesterol, triglycerides, glycated hemoglobin, and insulin levels and lower 2-h plasma insulin levels in glucose tolerance tests. The lowering of plasma insulin concentrations with little effect on glucose concentrations suggests that the supplement increases insulin sensitivity. The cation after 12 and 22 or 24 weeks of administration lowers (P < 0.05) fasting plasma glycated hemoglobin levels in the Zucker diabetic and Zucker obese rats, respectively, and thus can improve the glucose status of the diabetic models. The effects cannot be attributed to the propionate ligand.

Animals↗

The biomimetic [Cr3O(O2CCH2CH3)6(H2O)3]+ decreases plasma cholesterol and triglycerides in rats: towards chromium-containing therapeutics.

The in vivo effects of administration of the synthetic, functional biomimetic [Cr3O(O2CCH2CH3)6(H2O)3]+ 1 and a naturally occurring, biologically active form of chromium, low-molecular-weight chromium-binding substance (LMWCr), to rats are described. Given that the complexes are proposed to function by interacting with insulin receptor, trapping it in its active conformation, in contrast to current chromium-containing nutrition supplements, which only serve as sources of absorbable chromium, changes in lipid and carbohydrate metabolism would be expected. After 12 weeks administration (20 micrograms/kg body mass), compound 1 results in 40% lower levels of blood plasma LDL cholesterol, 33% lower levels of total cholesterol, and significantly lower HDL cholesterol and triglyceride; these results are in stark contrast to those of administration of other forms of Cr(III) to rats, which have no effect on these parameters. LMWCr, in contrast to 1, has no effect as it probably is degraded in vivo or excreted. These results are interpreted in terms of the mechanism of chromium action in response to insulin and the activation of insulin receptor, and the potential for the rational design of chromium-containing therapeutics is discussed.

Animals↗

The role of iron chelates on the selectivity of Fenton reagent in hydroxylation, N-demethylation, and sulfoxidation of cimetidine: a novel biomimetic model for the regioselectivity of cytochrome P-450.

The effect of iron chelates on the reaction of cimetidine with Fenton reagent [Fe(II)/H2O2] has been investigated. Iron chelates with high affinity to ferrous ions inhibited this reaction. However, iron chelates with high affinity to ferric ions selectively promote either hydroxylation, N-demethylation, or sulfoxidation of cimetidine. These results indicate that the oxidation of cimetidine with hydrogen peroxide activated by various chelated ferrous ions serves as a biomimetic model for the regioselectivity of multiple forms of cytochrome P-450 in the metabolism of cimetidine.

Cimetidine↗

Biomimetic oxidation of nonphenolic lignin models by Mn(III): new observations on the oxidizability of guaiacyl and syringyl substructures.

Mn(III) is a one-electron oxidant, produced in vivo by the Mn peroxidases of white-rot fungi, and thought to be involved in lignin degradation by these organisms. However, Mn(III) has not been shown to oxidize the major nonphenolic substructures of lignin under mild conditions. We have used Mn(III) acetate as a biomimetic model for enzymatically generated Mn(III), and report that low concentrations of this oxidant suffice to oxidize nonphenolic lignin models at physiological temperatures and pH values. Under these conditions, the monomeric lignin model veratryl alcohol was oxidized to veratraldehyde, and the diarylpropane model 1-(3,4-dimethoxyphenyl)-2-phenylpropanol was oxidatively cleaved to veratraldehyde, 1-phenylethanol, and acetophenone. In an attempt to identify other lignin models that might be oxidized by Mn(III) more rapidly, we compared the rates at which Mn(III) was reduced by two guaiacyl models, veratryl alcohol and 1-(3-methoxy-4-isopropoxyphenyl)ethanol, vs two syringyl models, 3,4,5-trimethoxybenzyl alcohol and 1-(3,5-dimethoxy-4-isopropoxyphenyl)ethanol. The results were the opposite of those predicted: the syringyl models were oxidized slower than the guaiacyl models by Mn(III). To investigate the basis for this unexpected result, we recorded the visible absorption spectra of charge-transfer complexes prepared between each of the lignin models and an electron acceptor, tetracyanoethylene or p-chloranil. The results, in general agreement with the kinetic findings, showed that the nonphenolic syringyl lignin models had higher ionization potentials than the guaiacyl models.

Biodegradation, Environmental↗

Biomimetic pulmonary surfactants.

Considerable progress has been made in the development of defined mixtures of proteins or peptides with phospholipids which mimic the activity of natural pulmonary surfactants. Several of these biomimetic surfactants are active in animal models and clinical syndromes of surfactant deficiency. This review summarizes the structure and composition of natural surfactants and the development of defined mixtures of peptides and lipids that may be useful in the treatment of respiratory distress.

Amino Acid Sequence↗

Activation of promutagens by porphyrinic biomimetic systems.

Biomimetic oxidative systems using tetraarylporphyrins, which can bind various metals, and exogenous oxygen donors have been extensively studied as models of the natural heme prosthetic group. Those systems were shown to catalyze oxidations in a manner consistent with cytochromes P-450 and usefully contributed to an understanding of the mechanisms of the cytochromes P-450-dependent reactions when using oxygen donors. The usage of those systems in mutagenicity studies showed that some promutagens could be activated to proximate mutagens. In the present work we report on the activation of benzo[a]pyrene, 3-methylcholanthrene, 7,12-dimethylbenz[a]anthracene; 2-aminofluorene, 2-acetylaminofluorene and the heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) to Ames assay mutagens using tetraphenylporphinatoiron(III) chloride and various oxygen donors, namely iodosylbenzene, cumene hydroperoxide, tert-butylhydroperoxide and H2O2. Our results demonstrate that IQ could be activated using any of the oxygen donors. However, a pattern of specificity for the oxygen donor could be identified. Polycyclic aromatic hydrocarbons displayed higher levels of mutagenicity with iodosylbenzene, whereas aromatic amines were preferentially activated when tert-butylhydroperoxide was used. For the heterocyclic amine IQ the higher responses were obtained using cumene hydroperoxide. The putative non-carcinogen pyrene and the controversial carcinogen quercetin were not activated irrespective of the oxygen donor used.

Dose-Response Relationship, Drug↗

Novel synthesis of 2-fluoroestradiol from 19-nortestosterone: biomimetic oxidative defluorination to 2-hydroxyestradiol.

A new, short synthetic route to 2-fluoroestradiol from 19-nortestosterone is described which gives the target compound in an approximately 25% overall yield. Oxidative defluorination of 2-fluoroestradiol to 2-hydroxyestradiol via treatment with Frémy's salt/iodide ion is reported. This process is regarded as biomimetic with respect to cytochrome P-450-dependent oxidative defluorination.

Chemical Phenomena↗

Designer dyes: 'biomimetic' ligands for the purification of pharmaceutical proteins by affinity chromatography.

Affinity chromatography has been extensively refined over the past few years to meet the more stringent criteria being placed on recombinant proteins as therapeutic products. New developments in the design of selective and stable ligands for affinity chromatography are establishing the technique as a routine tool in process-scale protein purification. Exploitation of sophisticated molecular modelling techniques in conjunction with binding and crystallographic studies has permitted the design of new, highly selective 'biomimetic' ligands for the target proteins.

Binding Sites↗

Biotechnology and biomimetic with crystalline bacterial cell surface layers (S-layers).

Crystalline bacterial cell surface layers (S-layers) are the outermost cell envelope component of many eubacteria and archaeobacteria. S-layers are composed of a single protein or glycoprotein species and exhibit oblique, square or hexagonal lattice symmetry. Pores passing through these monomolecular arrays show identical size and morphology, and functional groups are aligned in well-defined positions and orientations. Due to these unique features, S-layers have broad application potential in biotechnology including functioning as biomimetic membranes. Presently, S-layers are used (i) for the production of isoporous ultrafiltration membranes with very well defined molecular sieving and adsorption properties, (ii) as matrices for the controlled immobilization of biologically active macromolecules (e.g., enzymes, antibodies, ligands) as required for biosensors, affinity membranes and affinity microparticles as well as for solid phase assays, (iii) as stabilizing structures for Langmuir-Blodgett films and liposomes and (iv) as carriers and adjuvants for weakly immunogenic antigens and haptens.

Adjuvants, Immunologic↗

Metal partitioning in river sediments measured by sequential extraction and biomimetic approaches.

We quantified the concentrations and distributions of metals (Cd, Cr, Cu, Ni, Pb, and Zn) in the sediments of Tuen Mun River, Hong Kong. The potential bioavailability of metals was assessed with a biomimetic extraction method using the sipunculan gut juices. The sediments were characterized by relatively high concentrations of trace metals. Field collected sediments were highly anoxic and the ratio of simultaneously extractable metal (sigmaSEM) to acid volatile sulfide (AVS) was much less than one in these sediments. The majority (>67%) of Cd, Pb, and Zn were bound to AVS, thus their concentrations in the sediment porewater were low. In contrast, Ni was little bound to AVS due to its lower ratios of SEM-Ni to total Ni concentrations. For Cu, relatively high concentrations in the sediment porewater was found, and total organic carbon, AVS and other resistant sulfide phase were the controlling factors for sedimentary Cu partitioning. Net metal adsorption from gut juices to anoxic sediments was observed in metal extraction experiments, suggesting that AVS determined the bioaccumulation and potential bioavailability of most metals in these sediments. Extraction of metals from the oxidized sediments by the gut juices was mainly attributed to metal redistribution from AVS to other geochemical phases. The gut juices were the most effective solvent or extractant than the simple electrolyte solution [I (NaNO(3)) = 0.01 M] and the natural overlying water. Cd was more easily extracted from the oxidized sediments than Zn that tended to have a stronger binding affinity with Fe-Mn oxide, clay and organic matter. The application of partial removal techniques in metal extraction experiments further demonstrated the differential controls of various sediment geochemical phases in affecting metal bioavailability, with the order of TOC > Fe-Mn oxides > carbonate.

Animals↗

Biomimetic oxidation of lignin model compounds by simple inorganic complexes.

Copper peroxydisulfate has been shown to mimic "ligninases" in the oxidative degradation of Dihydroanisoin, Veratrylglycerol-beta-guaiacyl ether and veratryl alcohol. A unified mechanism leads to predictable degradative pathways. These are initiated by single-electron oxidation of aromatic substrates to aryl cation radicals as common intermediates to both the enzymic and biomimetic reactions. Our preliminary results show that simple complexes can facilitate the oxidative degradation of lignin model compounds.

Anisoles↗

Characterization of biomimetic surfaces formed from cell membranes.

A method for fabricating biomimetic surfaces from intact cell membranes is described. A monolayer of alkanethiol on gold is covered by a second layer derived from the components of erythrocyte membranes either by self-assembly or by Langmuir-Blodgett methods. The resulting asymmetric hybrid layer was characterized by ellipsometry, surface plasmon resonance (SPR), contact angle, capacitance, voltammetry, and electron and atomic force microscopy. The erythrocyte membrane layer was measured to be approximately 30-40 A in thickness. Using SPR, the presence of erythrocyte components on the surface was demonstrated by their selective removal by enzymatic action. The uniform deposition of membranous material on the substrate was shown by electron and atomic force microscopy. Demonstration of acetylcholinesterase (AChase) activity, a membrane-anchored enzyme, on the surface for at least 8 days, suggests that the outer leaflet of the erythrocyte membrane is present in its native form. Cyclic voltammetry demonstrates that enhanced electron transport from a solution redox species accompanies formation of the erythrocyte layer at the surface. This enhanced electron transport is blocked by 4,4'-diisothiocyanate stilbene-2,2'-disulfonic acid, a well known blocker of anion transport, suggesting that an erythrocyte anion transporter protein is incorporated into the surface layer in an active conformation.

Acetylcholinesterase↗

Biomimetic model of skeletal muscle isometric contraction: I. an energetic-viscoelastic model for the skeletal muscle isometric force twitch.

This paper describes a revision of the Hill-type muscle model so that it will describe the chemo-mechanical energy conversion process (energetic) and the internal-element stiffness variation (viscoelastic) during a skeletal muscle isometric force twitch contraction. The derivation of this energetic-viscoelastic model is described by a first-order linear ordinary differential equation with constant energetic and viscoelastic coefficients. The model has been implemented as part of a biomimetic model, which describes the excitation-contraction coupling necessary to drive the energetic-viscoelastic model. Finally, the energetic-viscoelastic model is validated by comparing its isometric force-time profile with that of various muscles reported in the literature.

Calcium↗

Biomimetic model of skeletal muscle isometric contraction: II. A phenomenological model of the skeletal muscle excitation-contraction coupling process.

This paper describes a new macroscopic, phenomenological model of the skeletal muscle excitation-contraction coupling process, as represented by four principal and consecutive compartments (biophysical, biochemical, and biomechanical phases) characteristic of isometric excitation-contraction coupling in mammalian skeletal muscle, and coupled by a system of simultaneous, first-order linear ordinary differential equations. The model is based upon biological compartmental transport kinetics and irreversible thermodynamic energy transformation, and represents a distinct improvement over other biomimetic models. The model was derived using physiological parameter data published in the literature, and validated using MATLAB R12.

Calcium↗

Advances in S-layer nanotechnology and biomimetics.

Two-dimensional crystalline bacterial S-layers composed of identical protein or glycoprotein subunits turned out to be ideal materials for the development of biomimetic membranes and new approaches in molecular nanotechnology. These isoporous protein lattices have already been used as (i) structure for producing isoporous ultrafiltration membranes with very precisely defined molecular sieving properties, (ii) matrices for immobilizing monolayers of functional molecules, (iii) stabilizing structure for LB-films and liposomes, and (iv) patterning elements in molecular nanotechnology.

Archaea↗

Synthesis of biomimetic Ca-hydroxyapatite powders at 37 degrees C in synthetic body fluids.

An important inorganic phase for synthetic bone applications, calcium hydroxyapatite (HA, Ca10(PO4)6(OH)2), was prepared as a nano-sized (approximately 50 nm), homogeneous and high-purity ceramic powder from calcium nitrate tetrahydrate and diammonium hydrogen phosphate salts dissolved in modified synthetic body fluid (SBF) solutions at 37 degrees C and pH of 7.4 using a novel chemical precipitation technique. The synthesized precursors were found to easily reach a phase purity >99% after 6 h of calcination in air atmosphere at 90 degrees C, following oven drying at 80 degrees C. There was observed, surprisingly, no decomposition of HA into the undesired beta-TCP phase even after heating at 1,600 degrees C in air for 6 h. This observation showed the superior high-temperature stability of such 'biomimetic' HA powders as compared to those reported in previous studies. The former powders were also found to contain trace amounts of Na and Mg ions, originating from the use of SBF solutions instead of pure water during their synthesis. Characterization and chemical analysis of the synthesized powders were performed by X-ray powder diffraction, energy-dispersive X-ray spectroscopy, Fourier-transform infra-red spectroscopy, scanning electron microscopy, and inductively coupled plasma atomic emission spectroscopy.

Body Fluids↗

Biomimetic configurational arrays of hydroxyapatite nanocrystals on bio-organics.

Biomimetic configurational arrays of hydroxyapatite (HAp) nanocrystals on several bio-organics, collagen (Col), chondroitin sulfate (ChS), and their mixture, were comparatively studied. The nanocomposites of HAp/Col, HAp/ChS, and HAp/Col/ChS were synthesized through a precipitation method with calcium hydroxide suspension and phosphoric acid solution containing Col, ChS, and their mixture, respectively. The (0 0 2) diffraction of the synthesized HAp crystals on a Col fiber showed an around 60 arching angle, while that on a ChS fiber showed just around 10 degrees. The same configurational arrays of HAp crystals could also be obtained on the mixture of Col and ChS fibers. The different electron diffraction patterns of the HAp crystals on the Col and ChS fibers were explained by the different macromolecular configurations of the Col and ChS fibrils which compose their fibers. The results may be applicable to develop a bone substitute which mimics the peculiar configurational arrays of HAp crystals found in bone and their detailed organic composition.

Biocompatible Materials↗