Ferric Compounds: Inorganic or organic compounds containing trivalent iron.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Sulfur Compounds: Inorganic or organic compounds that contain sulfur as an integral part of the molecule.Volatile Organic Compounds: Organic compounds that have a relatively high VAPOR PRESSURE at room temperature.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Plant Extracts: Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.Drug Evaluation, Preclinical: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).Phenols: Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.Heterocyclic Compounds: Ring compounds having atoms other than carbon in their nuclei. (Grant & Hackh's Chemical Dictionary, 5th ed)Inhibitory Concentration 50: The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture.Biphenyl CompoundsSulfhydryl Compounds: Compounds containing the -SH radical.Small Molecule Libraries: Large collections of small molecules (molecular weight about 600 or less), of similar or diverse nature which are used for high-throughput screening analysis of the gene function, protein interaction, cellular processing, biochemical pathways, or other chemical interactions.Organotin Compounds: Organic compounds which contain tin in the molecule. Used widely in industry and agriculture.Aniline CompoundsSpiro Compounds: A group of compounds consisting in part of two rings sharing one atom (usually a carbon) in common.Nitrogen Compounds: Inorganic compounds that contain nitrogen as an integral part of the molecule.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Drug Design: The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Nitroso CompoundsOrganometallic Compounds: A class of compounds of the type R-M, where a C atom is joined directly to any other element except H, C, N, O, F, Cl, Br, I, or At. (Grant & Hackh's Chemical Dictionary, 5th ed)Organoselenium Compounds: Organic compounds which contain selenium as an integral part of the molecule.Drug Screening Assays, Antitumor: Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.Organophosphorus Compounds: Organic compounds that contain phosphorus as an integral part of the molecule. Included under this heading is broad array of synthetic compounds that are used as PESTICIDES and DRUGS.Azo CompoundsGas Chromatography-Mass Spectrometry: A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.Kinetics: The rate dynamics in chemical or physical systems.Epoxy Compounds: Organic compounds that include a cyclic ether with three ring atoms in their structure. They are commonly used as precursors for POLYMERS such as EPOXY RESINS.Volatilization: A phase transition from liquid state to gas state, which is affected by Raoult's law. It can be accomplished by fractional distillation.High-Throughput Screening Assays: Rapid methods of measuring the effects of an agent in a biological or chemical assay. The assay usually involves some form of automation or a way to conduct multiple assays at the same time using sample arrays.Quaternary Ammonium Compounds: Derivatives of ammonium compounds, NH4+ Y-, in which all four of the hydrogens bonded to nitrogen have been replaced with hydrocarbyl groups. These are distinguished from IMINES which are RN=CR2.Drug Discovery: The process of finding chemicals for potential therapeutic use.Polycyclic Compounds: Compounds consisting of two or more fused ring structures.p-Methoxy-N-methylphenethylamine: A potent mast cell degranulator. It is involved in histamine release.Hydrocarbons, Aromatic: Organic compounds containing carbon and hydrogen in the form of an unsaturated, usually hexagonal ring structure. The compounds can be single ring, or double, triple, or multiple fused rings.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.Benzyl CompoundsOrganic Chemicals: A broad class of substances containing carbon and its derivatives. Many of these chemicals will frequently contain hydrogen with or without oxygen, nitrogen, sulfur, phosphorus, and other elements. They exist in either carbon chain or carbon ring form.Terphenyl Compounds: Compounds consisting of benzene rings linked to each other in either ortho, meta or para positions. Permitted are any substitutions, but ring fusion to any of the benzene rings is not allowed.Cell Line, Tumor: A cell line derived from cultured tumor cells.TriterpenesFurans: Compounds with a 5-membered ring of four carbons and an oxygen. They are aromatic heterocycles. The reduced form is tetrahydrofuran.Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Molecular Conformation: The characteristic three-dimensional shape of a molecule.Allyl CompoundsModels, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Spectrophotometry, Ultraviolet: Determination of the spectra of ultraviolet absorption by specific molecules in gases or liquids, for example Cl2, SO2, NO2, CS2, ozone, mercury vapor, and various unsaturated compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Glycosides: Any compound that contains a constituent sugar, in which the hydroxyl group attached to the first carbon is substituted by an alcoholic, phenolic, or other group. They are named specifically for the sugar contained, such as glucoside (glucose), pentoside (pentose), fructoside (fructose), etc. Upon hydrolysis, a sugar and nonsugar component (aglycone) are formed. (From Dorland, 28th ed; From Miall's Dictionary of Chemistry, 5th ed)Heterocyclic Compounds, 2-Ring: A class of organic compounds containing two ring structures, one of which is made up of more than one kind of atom, usually carbon plus another atom. The heterocycle may be either aromatic or nonaromatic.PicratesSpectrophotometry, Infrared: Spectrophotometry in the infrared region, usually for the purpose of chemical analysis through measurement of absorption spectra associated with rotational and vibrational energy levels of molecules. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Selenium Compounds: Inorganic compounds that contain selenium as an integral part of the molecule.Plant Bark: The outer layer of the woody parts of plants.Plants, Medicinal: Plants whose roots, leaves, seeds, bark, or other constituent parts possess therapeutic, tonic, purgative, curative or other pharmacologic attributes, when administered to man or animals.Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Quantitative Structure-Activity Relationship: A quantitative prediction of the biological, ecotoxicological or pharmaceutical activity of a molecule. It is based upon structure and activity information gathered from a series of similar compounds.Indicators and Reagents: Substances used for the detection, identification, analysis, etc. of chemical, biological, or pathologic processes or conditions. Indicators are substances that change in physical appearance, e.g., color, at or approaching the endpoint of a chemical titration, e.g., on the passage between acidity and alkalinity. Reagents are substances used for the detection or determination of another substance by chemical or microscopical means, especially analysis. Types of reagents are precipitants, solvents, oxidizers, reducers, fluxes, and colorimetric reagents. (From Grant & Hackh's Chemical Dictionary, 5th ed, p301, p499)Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.Trialkyltin Compounds: Organometallic compounds which contain tin and three alkyl groups.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Plant Components, Aerial: The above-ground plant without the roots.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.Bicyclo CompoundsBiodegradation, Environmental: Elimination of ENVIRONMENTAL POLLUTANTS; PESTICIDES and other waste using living organisms, usually involving intervention of environmental or sanitation engineers.Chromatography, Thin Layer: Chromatography on thin layers of adsorbents rather than in columns. The adsorbent can be alumina, silica gel, silicates, charcoals, or cellulose. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Microbial Sensitivity Tests: Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).SesquiterpenesDiterpenes: Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate.Biological Products: Complex pharmaceutical substances, preparations, or matter derived from organisms usually obtained by biological methods or assay.
Sodium ferric gluconate complexCapravirineTo Kau Wan: To Kau Wan () is a bay on the north shore of northeast Lantau Island, Hong Kong. Contaminated soil from Penny's Bay was transferred here for thermal desorption to separate the Volatile Organic Compounds (VOC) and Semi-Volatile Organic Compounds (SVOC) along with cement immobilization of metal contamination from Penny's Bay.Ethyl groupPhytomedicineSpin–lattice relaxation in the rotating frame: Spin–lattice relaxation in the rotating frame is the mechanism by which Mxy, the transverse component of the magnetization vector, exponentially decays towards its equilibrium value of zero, under the influence of a radio frequency (RF) field in nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). It is characterized by the spin–lattice relaxation time constant in the rotating frame, T1ρ.AlkylphenolHeterocyclic amine: Heterocyclic amines, also sometime referred to as HCAs, are chemical compounds containing at least one heterocyclic ring, which by definition has atoms of at least two different elements, as well as at least one amine (nitrogen-containing) group. Typically it is a nitrogen atom of an amine group that also makes the ring heterocyclic (e.IrbesartanPerchloromethyl mercaptanDNA-encoded chemical library: DNA-encoded chemical libraries (DEL) is a technology for the synthesis and screening of collections of small molecule compounds of unprecedented size. DEL is used in medicinal chemistry to bridge the fields of combinatorial chemistry and molecular biology.Organotin chemistryStanley SpiroNitrogen trichlorideHigh-performance liquid chromatography: High-performance liquid chromatography (HPLC; formerly referred to as high-pressure liquid chromatography), is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pass a pressurized liquid solvent containing the sample mixture through a column filled with a solid adsorbent material.Sharpless asymmetric dihydroxylation: Sharpless asymmetric dihydroxylation (also called the Sharpless bishydroxylation) is the chemical reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to form a vicinal diol.Concentration effect: In the study of inhaled anesthetics, the concentration effect is the increase in the rate that the Fa(alveolar concentration)/Fi(inspired concentration) ratio rises as the alveolar concentration of that gas is increased. In simple terms, the higher the concentration of gas administered, the faster the alveolar concentration of that gas approaches the inspired concentration.Nitrosation: Nitrosation is a process of converting organic compounds into nitroso derivatives, i.e.Metallocene: A metallocene is a compound typically consisting of two cyclopentadienyl anions (Cp, which is C5H5−) bound to a metal center (M) in the oxidation state II, with the resulting general formula (C5H5)2M. Closely related to the metallocenes are the metallocene derivatives, e.Diphenyl diselenideChloro(cyclopentadienyl)bis(triphenylphosphine)rutheniumAzodicarbonamideGas chromatography–mass spectrometry: right|300 px|Example of a GC-MS instrument|thumbBurst kinetics: Burst kinetics is a form of enzyme kinetics that refers to an initial high velocity of enzymatic turnover when adding enzyme to substrate. This initial period of high velocity product formation is referred to as the "Burst Phase".Epoxidized soybean oilAmmonia volatilization from urea: Urea (46-0-0) accounts for more than fifty percent of the world’s nitrogenous fertilizers.Schwab, G.High throughput biologyTetramethylammonium chlorideFragment-based lead discovery: Fragment-based lead discovery (FBLD) also known as fragment-based drug discovery (FBDD) is a method used for finding lead compounds as part of the drug discovery process. It is based on identifying small chemical fragments, which may bind only weakly to the biological target, and then growing them or combining them to produce a lead with a higher affinity.AromaticityAntileukemic drug: Antileukemic drugs, anticancer drugs that are used to treat one or more types of leukemia, include:Atomic mass: right |thumb|200px|Stylized [[lithium-7 atom: 3 protons, 4 neutrons, & 3 electrons (total electrons are ~1/4300th of the mass of the nucleus). It has a mass of 7.Dibenzyl ketonePrinomastatTerphenylHopanoids: Hopanoids are natural pentacyclic compounds (containing five rings) based on the chemical structure of hopane. The first known triterpenoid of the class, hydroxyhopanone, was isolated by two chemists at The National Gallery, London working on the chemistry of dammar gum, a natural resin used as a varnish for paintings.MethanofuranTable of standard reduction potentials for half-reactions important in biochemistry: The values below are standard reduction potentials for half-reactions measured at 25°C, 1 atmosphere and a pH of 7 in aqueous solution.Organosulfur compounds: Organosulfur compounds are organic compounds that contain sulfur. They are often associated with foul odors, but many of the sweetest compounds known are organosulfur derivatives, e.Reaction coordinateGlycoside: In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms.Basic aromatic ring: Basic aromatic rings are aromatic rings in which the lone pair of electrons of a ring-nitrogen atom is not part of the aromatic system and extends in the plane of the ring. This lone pair is responsible for the basicity of these nitrogenous bases, similar to the nitrogen atom in amines.Potassium picrateTwo-dimensional infrared spectroscopySodium selenideCarl Barks: "United States Social Security Death Index," index, FamilySearch (https://familysearch.org/pal:/MM9.Medicinal plants of the American West: Many plants that grow in the American West have use in traditional and herbal medicine.BacitracinTherapeutic Targets Database: Therapeutic Target Database (TTD) is a database provided by Bioinformatics and Drug Design Group in National University of Singapore, which provides information about the known and explored therapeutic protein and nucleic acid targets, the targeted disease, pathway information and the corresponding drugs directed at each of these targets. Also included in this database are links to relevant databases containing information about target function, sequence, 3D structure, ligand binding properties, enzyme nomenclature and drug structure, therapeutic class, clinical development status.Biotransformation: Biotransformation is the chemical modification (or modifications) made by an organism on a chemical compound. If this modification ends in mineral compounds like CO2, NH4+, or H2O, the biotransformation is called mineralisation.Acetyl tributyl citrate: Acetyl tributyl citrate is valued as a biodegradable plasticizer of low toxicity, found in nail polish and other cosmetics.Coles PhillipsShatter (novel): Shatter is a psychological thriller written by the Australian author Michael Robotham that was published in 2008. Professor Joseph O'Loughlin (referred to as Joe throughout the novel) is tasked by the police with stopping a woman, Christine Wheeler, from committing suicide, only to fail.BiodegradationChromatographic response function: Chromatographic response function, often abbreviated to CRF, is a coefficient which measures the quality of the separation in the result of a chromatography.Sesquiterpene lactone: Sesquiterpene lactones are a class of chemical compounds; they are sesquiterpenoids (built from three isoprene units) and contain a lactone ring, hence the name. They are found in many plants and can cause allergic reactions and toxicity if overdosed, particularly in grazing livestock.Momilactone BChina Biologic Products, Inc.
(1/2363) Inhibition of vibrio anguillarum by Pseudomonas fluorescens AH2, a possible probiotic treatment of fish.
To study the possible use of probiotics in fish farming, we evaluated the in vitro and in vivo antagonism of antibacterial strain Pseudomonas fluorescens strain AH2 against the fish-pathogenic bacterium Vibrio anguillarum. As iron is important in virulence and bacterial interactions, the effect of P. fluorescens AH2 was studied under iron-rich and iron-limited conditions. Sterile-filtered culture supernatants from iron-limited P. fluorescens AH2 inhibited the growth of V. anguillarum, whereas sterile-filtered supernatants from iron-replete cultures of P. fluorescens AH2 did not. P. fluorescens AH2 inhibited the growth of V. anguillarum during coculture, independently of the iron concentration, when the initial count of the antagonist was 100 to 1, 000 times greater that of the fish pathogen. These in vitro results were successfully repeated in vivo. A probiotic effect in vivo was tested by exposing rainbow trout (Oncorynchus mykiss Walbaum) to P. fluorescens AH2 at a density of 10(5) CFU/ml for 5 days before a challenge with V. anguillarum at 10(4) to 10(5) CFU/ml for 1 h. Some fish were also exposed to P. fluorescens AH2 at 10(7) CFU/ml during the 1-h infection. The combined probiotic treatment resulted in a 46% reduction of calculated accumulated mortality; accumulated mortality was 25% after 7 days at 12 degrees C in the probiotic-treated fish, whereas mortality was 47% in fish not treated with the probiont. (+info)
(2/2363) Dissimilatory reduction of Fe(III) and other electron acceptors by a Thermus isolate.
A thermophilic bacterium that can use O2, NO3-, Fe(III), and S0 as terminal electron acceptors for growth was isolated from groundwater sampled at a 3.2-km depth in a South African gold mine. This organism, designated SA-01, clustered most closely with members of the genus Thermus, as determined by 16S rRNA gene (rDNA) sequence analysis. The 16S rDNA sequence of SA-01 was >98% similar to that of Thermus strain NMX2 A.1, which was previously isolated by other investigators from a thermal spring in New Mexico. Strain NMX2 A.1 was also able to reduce Fe(III) and other electron acceptors. Neither SA-01 nor NMX2 A.1 grew fermentatively, i.e., addition of an external electron acceptor was required for anaerobic growth. Thermus strain SA-01 reduced soluble Fe(III) complexed with citrate or nitrilotriacetic acid (NTA); however, it could reduce only relatively small quantities (0.5 mM) of hydrous ferric oxide except when the humic acid analog 2,6-anthraquinone disulfonate was added as an electron shuttle, in which case 10 mM Fe(III) was reduced. Fe(III)-NTA was reduced quantitatively to Fe(II); reduction of Fe(III)-NTA was coupled to the oxidation of lactate and supported growth through three consecutive transfers. Suspensions of Thermus strain SA-01 cells also reduced Mn(IV), Co(III)-EDTA, Cr(VI), and U(VI). Mn(IV)-oxide was reduced in the presence of either lactate or H2. Both strains were also able to mineralize NTA to CO2 and to couple its oxidation to Fe(III) reduction and growth. The optimum temperature for growth and Fe(III) reduction by Thermus strains SA-01 and NMX2 A.1 is approximately 65 degrees C; their optimum pH is 6.5 to 7.0. This is the first report of a Thermus sp. being able to couple the oxidation of organic compounds to the reduction of Fe, Mn, or S. (+info)
(3/2363) Vitronectin inhibits the thrombotic response to arterial injury in mice.
Vitronectin (VN) binds to plasminogen activator inhibitor-1 (PAI-1) and integrins and may play an important role in the vascular response to injury by regulating fibrinolysis and cell migration. However, the role of VN in the earliest response to vascular injury, thrombosis, is not well characterized. The purpose of this study was to test the hypothesis that variation in vitronectin expression alters the thrombotic response to arterial injury in mice. Ferric chloride (FeCl3) injury was used to induce platelet-rich thrombi in mouse carotid arteries. Wild-type (VN +/+, n = 14) and VN-deficient (VN -/-, n = 15) mice, matched for age and gender, were studied. Time to occlusion after FeCl3 injury was determined by application of a Doppler flowprobe to the carotid artery. Occlusion times of VN -/- mice were significantly shorter than those of VN +/+ mice (6.0 +/- 1.2 minutes v 17.8 +/- 2.3 minutes, respectively, P < .001). Histologic analysis of injured arterial segments showed that thrombi from VN +/+ and VN -/- mice consisted of dense platelet aggregates. In vitro studies of murine VN +/+ and VN -/- platelets showed no significant differences in ADP-induced aggregation, but a trend towards increased thrombin-induced aggregation in VN -/- platelets. Purified, denatured VN inhibited thrombin-induced platelet aggregation, whereas native VN did not. Thrombin times of plasma from VN -/- mice (20.5 +/- 2.1 seconds, n = 4) were significantly shorter than those of VN +/+ mice (34.2 +/- 6.7 seconds, n = 4, P < .01), and the addition of purified VN to VN -/- plasma prolonged the thrombin time into the normal range, suggesting that VN inhibits thrombin-fibrinogen interactions. PAI-1-deficient mice (n = 6) did not demonstrate significantly enhanced arterial thrombosis compared with wild-type mice (n = 6), excluding a potential indirect antithrombin function of VN mediated by interactions with PAI-1 as an explanation for the accelerated thrombosis observed in VN -/- mice. These results suggest that vitronectin plays a previously unappreciated antithrombotic role at sites of arterial injury and that this activity may be mediated, at least in part, by inhibiting platelet-platelet interactions and/or thrombin procoagulant activity. (+info)
(4/2363) Down regulation by iron of prostaglandin E2 production by human synovial fibroblasts.
OBJECTIVE: To examine the effect of iron on the prostaglandin (PG) E2 production by human synovial fibroblasts in vitro. METHODS: Human synovial fibroblasts were isolated from synovial tissue of rheumatoid arthritis (RA) and osteoarthritis (OA) patients and cultured in medium. Synovial fibroblasts were stimulated by human recombinant interleukin (IL) 1 beta (0.1-10 ng/ml) with or without ferric citrate (Fe-citrate, 0.01-1 mM). The amount of PGE2 in the culture medium was measured by an enzyme linked immunosorbent assay. RESULTS: The production of PGE2 by the synovial fibroblasts was increased by stimulation with IL1 beta at all concentrations tested. Fe-citrate but not sodium citrate (Na-citrate) down regulated the production of PGE2 by the synovial fibroblasts, both with and without stimulation by IL1 beta. Fe-citrate inhibited the spontaneous PGE2 production by the cells in a dose dependent manner, and a maximum inhibition by Fe-citrate was observed at the concentration of 0.1 mM with IL1 beta stimulation. The down regulation by iron was reversed by the co-addition of desferrioxamine (100 micrograms/ml), an iron chelator. CONCLUSION: Iron down regulates the PGE2 production by synovial fibroblasts in vitro. (+info)
(5/2363) IC202A, a new siderophore with immunosuppressive activity produced by Streptoalloteichus sp. 1454-19. I. Taxonomy, fermentation, isolation and biological activity.
IC202A, a new immunosuppressive compound, was isolated from the culture filtrate of Streptoalloteichus sp. 1454-19. It showed a suppressive effect on mixed lymphocyte culture reaction with an IC50 value of 3.6 microg/ml and mitogen induced lymphocyte blastogenesis in vitro. (+info)
(6/2363) Amyloid beta peptides do not form peptide-derived free radicals spontaneously, but can enhance metal-catalyzed oxidation of hydroxylamines to nitroxides.
Amyloid beta (Abeta) peptides play an important role in the pathogenesis of Alzheimer's disease. Free radical generation by Abeta peptides was suggested to be a key mechanism of their neurotoxicity. Reports that neurotoxic free radicals derived from Abeta-(1-40) and Abeta-(25-35) peptides react with the spin trap N-tert-butyl-alpha-phenylnitrone (PBN) to form a PBN/.Abeta peptide radical adduct with a specific triplet ESR signal assert that the peptide itself was the source of free radicals. We now report that three Abeta peptides, Abeta-(1-40), Abeta-(25-35), and Abeta-(40-1), do not yield radical adducts with PBN from the Oklahoma Medical Research Foundation (OMRF). In contrast to OMRF PBN, incubation of Sigma PBN in phosphate buffer without Abeta peptides produced a three-line ESR spectrum. It was shown that this nitroxide is di-tert-butylnitroxide and is formed in the Sigma PBN solution as a result of transition metal-catalyzed auto-oxidation of the respective hydroxylamine present as an impurity in the Sigma PBN. Under some conditions, incubation of PBN from Sigma with Abeta-(1-40) or Abeta-(25-35) can stimulate the formation of di-tert-butylnitroxide. It was shown that Abeta peptides enhanced oxidation of cyclic hydroxylamine 1-hydroxy-4-oxo-2,2,6, 6-tetramethylpiperidine (TEMPONE-H), which was strongly inhibited by the treatment of phosphate buffer with Chelex-100. It was shown that ferric and cupric ions are effective oxidants of TEMPONE-H. The data obtained allow us to conclude that under some conditions toxic Abeta peptides Abeta-(1-40) and Abeta-(25-35) enhance metal-catalyzed oxidation of hydroxylamine derivatives, but do not spontaneously form peptide-derived free radicals. (+info)
(7/2363) A physiological barrier distal to the anatomic blood-brain barrier in a model of transvascular delivery.
BACKGROUND AND PURPOSE: Osmotic disruption of the blood-brain barrier (BBB) provides a method for transvascular delivery of therapeutic agents to the brain. The apparent global delivery of viral-sized iron oxide particles to the rat brain after BBB opening as seen on MR images was compared with the cellular and subcellular location and distribution of the particles. METHODS: Two dextran-coated superparamagnetic monocrystalline iron oxide nanoparticle contrast agents, MION and Feridex, were administered intraarterially in rats at 10 mg Fe/kg immediately after osmotic opening of the BBB with hyperosmolar mannitol. After 2 to 24 hours, iron distribution in the brain was evaluated first with MR imaging then by histochemical analysis and electron microscopy to assess perivascular and intracellular distribution. RESULTS: After BBB opening, MR images showed enhancement throughout the disrupted hemisphere for both Feridex and MION. Feridex histochemical staining was found in capillaries of the disrupted hemisphere. Electron microscopy showed that the Feridex particles passed the capillary endothelial cells but did not cross beyond the basement membrane. In contrast, after MION delivery, iron histochemistry was detected within cell bodies in the disrupted hemisphere, and the electron-dense MION core was detected intracellularly and extracellularly in the neuropil. CONCLUSION: MR images showing homogeneous delivery to the brain at the macroscopic level did not indicate delivery at the microscopic level. These data support the presence of a physiological barrier at the basal lamina, analogous to the podocyte in the kidney, distal to the anatomic (tight junction) BBB, which may limit the distribution of some proteins and viral particles after transvascular delivery to the brain. (+info)
(8/2363) Iron reductase for magnetite synthesis in the magnetotactic bacterium Magnetospirillum magnetotacticum.
Ferric iron reductase was purified from magnetotactic bacterium Magnetospirillum (formerly Aquaspirillum) magnetotacticum (ATCC 31632) to an electrophoretically homogeneous state. The enzyme was loosely bound on the cytoplasmic face of the cytoplasmic membrane and was found more frequently in magnetic cells than in nonmagnetic cells. The molecular mass of the purified enzyme was calculated upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis to be about 36 kDa, almost the same as that calibrated by gel filtration analysis. The enzyme required NADH and flavin mononucleotide (FMN) as optimal electron donor and cofactor, respectively, and the activity was strongly inhibited by Zn2+ acting as a partial mixed-type inhibitor. The Km values for NADH and FMN were 4.3 and 0. 035 microM, respectively, and the Ki values for Zn2+ were 19.2 and 23.9 microM for NADH and FMN, respectively. When the bacterium was grown in the presence of ZnSO4, the magnetosome number in the cells and the ferric iron reductase activity declined in parallel with an increase in the ZnSO4 concentration of the medium, suggesting that the ferric iron reductase purified in the present study may participate in magnetite synthesis. (+info)