The effect of DMSA-functionalized magnetic nanoparticles on transendothelial migration of monocytes in the murine lung via a beta(2) integrin-dependent pathway

Magnetic nanoparticles surface-functionalized with meso-2,3-dimercaptosuccinic acid (MNPs-DMSA) constitute an innovative and promising approach for tissue- and cell-targeted delivery of therapeutic drugs in the lung. Transendothelial migration of leukocytes in the lung is a side effect of endovenous administration of MNPs-DMSA. Using cytologic and phenotypic analysis of murine bronchoalveolar lavage cells, we identified monocytes/macrophages as the main subpopulation of leukocytes involved in this process. Moreover, ultrastructural analysis revealed the presence of nanoparticles inside of numerous macrophages from bronchoalveolar lavage. MNPs-DMSA at concentrations as high as 1 X 10(15) nanoparticles/mL had no toxic effects on macrophages, as evidenced by 3-(4, 5-dimethylthiazolyi-2)-2,5-diphenyltetrazolium bromide (MTT) assay. Notably, MNPs-DMSA up-regulated the mRNA expression of E, L- and P-selectin and macrophage-1 antigen in the murine lung. Upregulation of these cell adhesion molecules was associated with an increased concentration of tumor necrosis factor-alpha in lung. Finally, the critical relevance of the beta(2) integrin-dependent pathway in leukocyte transmigration elicited by MNPs-DMSA was demonstrated by use of knockout mice. Our results characterize mechanisms of the pro-inflammatory effects of MNPs-DMSA in the lung, and identify beta(2) integrin-targeted interventions as promising strategies to reduce pulmonary side effects of MNPs-DMSA during biomedical applications. (C) 2009 Elsevier Ltd. All rights reserved.

The novel ruthenium-gamma-linolenic complex [Ru(2)(aGLA)(4)Cl] inhibits C6 rat glioma cell proliferation and induces changes in mitochondrial membrane potential, increased reactive oxygen species generation and apoptosis in vitro

The present study reports the synthesis of a novel compound with the formula [Ru(2)(aGLA)(4)Cl] according to elemental analyses data, referred to as Ru(2)GLA. The electronic spectra of Ru(2)GLA is typical of a mixed valent diruthenium(II,III) carboxylate. Ru(2)GLA was synthesized with the aim of combining and possibly improving the anti-tumour properties of the two active components ruthenium and gamma-linolenic acid (GLA). The properties of Ru(2)GLA were tested in C6 rat glioma cells by analysing cell number, viability, lipid droplet formation, apoptosis, cell cycle distribution, mitochondrial membrane potential and reactive oxygen species. Ru(2)GLA inhibited cell proliferation in a time and concentration dependent manner. Nile Red staining suggested that Ru(2)GLA enters the cells and ICP-AES elemental analysis found all increase in ruthenium from <0.02 to 425 mg/Kg in treated cells. The sub-G1 apoptotic cell population was increased by Ru(2)GLA (22 +/- 5.2%) when analysed by FACS and this was confirmed by Hoechst staining of nuclei. Mitochondrial membrane potential was decreased in the presence of Ru(2)GLA (44 +/- 2.3%). In contrast, the cells which maintained a high mitochondrial membrane potential had an increase (18 +/- 1.5%) in reactive oxygen species generation. Both decreased mitochondrial membrane potential and increased reactive oxygen species generation may be involved in triggering apoptosis in Ru(2)GLA exposed cells. The EC(50) for Ru(2)GLA decreased with increasing time of exposure from 285 mu M at 24h, 211 mu M at 48 h to 81 mu M at 72 h. In conclusion, Ru(2)GLA is a novel drug with anti proliferative properties in C6 glioma cells and is a potential candidate for novel therapies in gliomas. Copyright (C) 2009 John Wiley & Sons, Ltd.

Gamma Knife(A (R)) 3-D Dose Distribution Mapping by Magnetic Resonance Imaging

In medical processes where ionizing radiation is used, dose planning and dose delivery are the key elements to patient safety and treatment success, particularly, when the delivered dose in a single session of treatment can be an order of magnitude higher than the regular doses of radiotherapy. Therefore, the radiation dose should be well defined and precisely delivered to the target while minimizing radiation exposure to surrounding normal tissues [1]. Several methods have been proposed to obtain three-dimensional (3-D) dose distribution [2, 3]. In this paper, we propose an alternative method, which can be easily implemented in any stereotactic radiosurgery center with a magnetic resonance imaging (MRI) facility. A phantom with or without scattering centers filled with Fricke gel solution is irradiated with Gamma Knife(A (R)) system at a chosen spot. The phantom can be a replica of a human organ such as head, breast or any other organ. It can even be constructed from a real 3-D MR image of an organ of a patient using a computer-aided construction and irradiated at a specific region corresponding to the tumor position determined by MRI. The spin-lattice relaxation time T (1) of different parts of the irradiated phantom is determined by localized spectroscopy. The T (1)-weighted phantom images are used to correlate the image pixels intensity to the absorbed dose and consequently a 3-D dose distribution with a high resolution is obtained.

Temperature Dependence of Rb(2) Molecule Formation Rate Constant in a Magneto-Optical Trap

In this paper, we report the measurement of Rb(2) molecule formation rate constant due to a two body process in a magneto-optical trap as a function of the sample temperature. The ground state molecules are detected by two-photon ionization, through the intermediate a(3)Sigma(+)(u) -> 2(3)Pi(g) molecular band. Our results show that the Rb(2) molecules formed in the MOT could be due to a wave shape resonance, which enhances the molecule formation rate. This effect may be used to enhance the molecule production; and therefore it maybe important to future experiments involving production and trapping of cold ground state molecules.

Copper(II) and zinc(II) complexes with 2-formylpyridine-derived hydrazones

In the present work 2-formylpyridine-para-chloro-phenyl hydrazone (H2FopCIPh) and 2-formylpyridine-para-nitro-phenyl hydrazone (H2FopNO(2)Ph) were obtained, as well as their copper(II) and zinc(II) complexes [Cu(H2FopClPh)Cl(2)] (1), [Cu(2FopNO(2)Ph)Cl] (2), [Zn(H2FopClPh)Cl(2)] (3) and [Zn(H2FopNO(2)Ph)Cl(2)] (4). Upon re-crystallization in DMSO:acetone conversion of 2 into [Cu(2FopNO(2)Ph)Cl(DMSO)] (2a) and of 4 into [Zn(2FopNO(2)Ph)Cl(DMSO)] (4a) occurred. The crystal structures of 1, 2a, 3 and 4a were determined. (C) 2009 Elsevier Ltd. All rights reserved.

Binuclear zinc(II) complexes with the anti-inflammatory compounds salicylaldehyde semicarbazone and salicylaldehyde-4-chlorobenzoyl hydrazone (H(2)LASSBio-1064)

Complexes [Zn(2)(HL(1))(2)(CH(3)COO)(2)] (1) and [Zn(2)(L(2))(2)] (2) were synthesized with salicylaldehyde semicarbazone (H(2)L(1)) and salicylaldehyde-4-chlorobenzoyl hydrazone (H(2)LASSBio-1064, H(2)L(2)), respectively. The crystal structure of (1) was determined. Upon recrystallization of previously prepared [Zn(2)(HL(2))(2)(Cl)(2)] (3) in 1:9 DMSO:acetone crystals of [Zn(2)(L(2))(2)(H(2)O)(2)]center dot[Zn(2)(L(2))(2)(DMSO)(4)] (3a) were obtained. The crystal structure of 3a was also determined. All crystal structures revealed the presence of phenoxo-bridged binuclear zinc(II) complexes. (C) 2011 Elsevier Ltd. All rights reserved.

Structural studies on zinc(II) complexes with 2-benzoylpyridine-derived hydrazones

2-Benzoylpyridine-phenylhydrazone (H2BzPh), 2-benzoylpyridine-para-chloro-phenylhydrazone (H2BzpClPh), and 2-benzoylpyridine-para-nitro-phenyl (H2BzpNO(2)Ph) hydrazone were obtained and fully characterized, as well as their zinc(II) complexes [Zn(H2BzPh)Cl(2)] (1), [Zn(H2BzClPh)Cl(2)] (2) and [Zn(H2BzpNO(2)Ph)Cl(2)] (3). During the syntheses of complex 1 a second product crystallized, which was characterized as [Zn(2BzPh)(2)] (1a). Upon re-crystallization in 1: 9 DMSO: acetone conversion of 2 into [Zn(H2BzpClPh)Cl2] center dot H(2)O (2a) and of 3 into [Zn(2BzpNO(2)Ph)Cl(DMSO)] (3a) occurred. The crystal structures of 1a, 2a and 3a were determined. In 1a the two nearly perpendicular H2BzPh ligands give rise to a distorted octahedral environment around the metal. The 5-fold coordination around the metal is completed with two chloride ions in 2a and with one chloride and one oxygen atom from DMSO in 3a. (c) 2008 Elsevier B.V. All rights reserved.

Reactions of 1,2.,5-thiadiazole 1,1-dioxide derivatives with nitrogen nucleophiles. Part IV. Addition of alpha-diamines

alpha-diamines, such as ethylendiamine and o-phenylendiamine, add to 3,4-aryl-disubstituted 1,2,5-thiadiazole 1,1-dioxides to give dihydropyrazines or quinoxalines, respectively and sulfamide. The new compound acenaphtho [5,6-b]-2,3-dihydropyrazine was synthesized and characterized. The addition of ethylendiamine to 3,4-diphenyl-1,2,5-thiadiazoline 1,1-dioxide gives 3,4-disubstituted thiadiazoildine 1,1-dioxide, dihydropyrazines, or pyrazines, depending on the reaction condition used. The reactions were followed by cyclic voltammetry and NMR spectroscopy which, in some cases, allowed the detection of the thiadiazolidine intermediate. Copyright (c) 2008 John Wiley & Sons, Ltd.

Energy transfer processes in Yb(3+)-Tm(3+) co-doped sodium alumino-phosphate glasses with improved 1.8 mu m emission

Sodium alumino-phosphate glasses co-doped with Yb(3+) and Tm(3+) ions have been prepared with notably low OH(-) content, and characterized from the viewpoint of their spectroscopic properties. In these glasses, Yb(3+) acts as an efficient sensitizer of excitation energy at 0.98 mu m - which can be provided by high power and low cost diode lasers, and subsequently undergoes non-resonant energy transfer to Tm(3+) ions ((2)F(5/2), (3)H(6) --> (2)F(7/2), (3)H(5)). Through this process, the emitting level (3)F(4) is rapidly populated, generating improved emission at 1.8 mu m ((3)F(4) --> (3)H(6)). In order to guarantee the efficiency of such favorable energy transfer, energy losses via multiphonon decay, Yb-Yb radiative trapping, and non- radiative transfer to OH(-) groups were evaluated, and minimized when possible. The dipole - dipole energy transfer microscopic parameters corresponding to Yb(3+) --> Tm(3+), Yb(3+) --> Yb(3+) and Tm(3+) --> Tm(3+) transfers, calculated by the Forster-Dexter model, are C(Yb-Tm) = 2.9 x 10(-40) cm(6) s(-1), C(Yb-Yb) = 42 x 10(-40) cm(6) s(-1) and C(Tm-Tm) = 43 x 10(-40) cm(6) s(-1), respectively.

Examples of Self-Iterating Lie Algebras, 2

We study properties of self-iterating Lie algebras in positive characteristic. Let R = K[t(i)vertical bar i is an element of N]/(t(i)(p)vertical bar i is an element of N) be the truncated polynomial ring. Let partial derivative(i) = partial derivative/partial derivative t(i), i is an element of N, denote the respective derivations. Consider the operators v(1) = partial derivative(1) + t(0)(partial derivative(2) + t(1)(partial derivative(3) + t(2)(partial derivative(4) + t(3)(partial derivative(5) + t(4)(partial derivative(6) + ...))))); v(2) = partial derivative(2) + t(1)(partial derivative(3) + t(2)(partial derivative(4) + t(3)(partial derivative(5) + t(4)(partial derivative(6) + ...)))). Let L = Lie(p)(v(1), v(2)) subset of Der R be the restricted Lie algebra generated by these derivations. We establish the following properties of this algebra in case p = 2, 3. a) L has a polynomial growth with Gelfand-Kirillov dimension lnp/ln((1+root 5)/2). b) the associative envelope A = Alg(v(1), v(2)) of L has Gelfand-Kirillov dimension 2 lnp/ln((1+root 5)/2). c) L has a nil-p-mapping. d) L, A and the augmentation ideal of the restricted enveloping algebra u = u(0)(L) are direct sums of two locally nilpotent subalgebras. The question whether u is a nil-algebra remains open. e) the restricted enveloping algebra u(L) is of intermediate growth. These properties resemble those of Grigorchuk and Gupta-Sidki groups.

Ca(2+)-mediated thiolysis of peptide-resin linkage as an option for preparing protected peptide thioesters

A mild new procedure for preparing protected peptide thioesters, based oil Ca(2+)-assisted thiolysis of peptide-Kaiser oxime resin (KOR) linkage, is described. Ac-Ile-Ser(Bzl)-Asp(OcHx)-SR (Ac: acetyl; Bzl: benzyl; cHx: cyclohexyl), model peptide, was readily released from the resin by incubating the peptide-KOR at 60 degrees C in mixtures of DMF with n-butanethiol [R = (CH(2))(3)CH(3)] or ethyl 3-mercaptopropionate [R = (CH(2))(2)COOCHCH(3)] containing Ca(CH(3)COO)(2). After serine and aspartic acid side-chain deprotection under acid conditions, Ac-Ile-Ser-Asp-S(CH(2))(2)COOCH(2)CH(3) was successfully obtained with good quality and high yield. This type of C-terminal modified peptide may act as an excellent acyl donor in peptide segment condensation by the thioester method, native chemical ligation and enzymatic methods. (c) 2008 Elsevier Ltd. All rights reserved.

Radical acetylation of 2`-deoxyguanosine and L-histidine coupled to the reaction of diacetyl with peroxynitrite in aerated medium

Diacetyl, like other alpha-dicarbonyl compounds, is reportedly cytotoxic and genotoxic. A food and cigarette contaminant, it is related with alcohol hepatotoxicity and lung disease. Peroxynitrite is a potent oxidant formed in vivo by the diffusion-controlled reaction of the superoxide radical anion with nitric oxide, which is able to form adducts with carbon dioxide and carbonyl compounds. Here, we investigate the nucleophilic addition of peroxynitrite to diacetyl forming acetyl radicals, whose reaction with molecular oxygen leads to acetate. Peroxynitrite is shown to react with diacetyl in phosphate buffer (bell-shaped pH profile with maximum at 7.2) at a very high rate constant (k(2) = 1.0 X 10(4) M-1 s(-1)) when compared with monocarbonyl substrates (k(2) < 10(3) M-1 s(-1)). Phosphate ions (100-500 MM) do not affect the rate of spontaneous peroxynitrite decay, but the H2PO4- anion catalyzes the nucleophilic addition of the peroxynitrite anion to diacetyl. The intermediacy of acetyl radicals is suggested by a three-line spectrum (a(N) = a(H) = 0.83 mT) obtained by EPR spin trapping of the reaction mixture with 2-methyl-2-nitrosopropane. The peroxynitrite reaction is accompanied by concentration-dependent oxygen uptake. Stoichiometric amounts of acetate from millimolar amounts of peroxynitrite and diacetyl were obtained under nonlimiting conditions of dissolved oxygen. In the presence of either L-histidine or 2`-deoxyguanosine, the peroxynitrite/diacetyl system afforded the corresponding acetylated molecules identified by HPLC-MS"". These studies provide evidence that the peroxynitrite/diacetyl reaction yields acetyl radicals and raise the hypothesis that protein and DNA nonenzymatic acetylation may occur in cells and be implicated in aging and metabolic disorders in which oxygen and nitrogen reactive species are putatively involved.

Effect of SO(2) on the Transport Properties of an Imidazolium Ionic Liquid and Its Lithium Solution

Transport coefficients have been measured as a function of the concentration of sulfur dioxide, SO(2), dissolved in 1-butyl-2,3-dimethylimidazolium bis(trifluoromethylsulfonyl)-imide, [BMMI][Tf(2)N], as well as in its lithium salt solution, Li[Tf(2)N]. The SO(2) reduces viscosity and density and increases conductivity and diffusion coefficients in both the neat [BMMI] [Tf(2)N] and the [BMMI][Tf(2)N]-Li[Tf(2)N] solution. The conductivity enhancement is not assigned to a simple viscosity effect; the weakening of ionic interactions upon SO(2) addition also plays a role. Microscopic details of the SO(2) effect were unraveled using Raman spectroscopy and molecular dynamics (MD) simulations. The Raman spectra suggest that the Li(+)-[Tf(2)N] interaction is barely affected by SO(2), and the SO(2)-[Tf(2)N] interaction is weaker than previously observed in an investigation of an ionic liquid containing the bromide anion. Transport coefficients calculated by MD simulations show the same trend as the experimental data with respect to SO(2) content. The MD simulations provide structural information on SO(2) molecules around [Tf(2)N], in particular the interaction of the sulfur atom of SO(2) with oxygen and fluorine atoms of the anion. The SO(2)-[BMMI] interaction is also important because the [BMMI] cations with above-average mobility have a larger number of nearest-neighbor SO(2) molecules.

Flow injection analysis of ethyl xanthate by gas diffusion and UV detection as CS(2) for process monitoring of sulfide ore flotation

A sensitive and robust analytical method for spectrophotometric determination of ethyl xanthate, CH(3)CH(2)OCS(2)(-) at trace concentrations in pulp solutions from froth flotation process is proposed. The analytical method is based on the decomposition of ethyl xanthate. EtX(-), with 2.0 mol L(-1) HCl generating ethanol and carbon disulfide. CS(2). A gas diffusion cell assures that only the volatile compounds diffuse through a PTFE membrane towards an acceptor stream of deionized water, thus avoiding the interferences of non-volatile compounds and suspended particles. The CS(2) is selectively detected by UV absorbance at 206 nm (epsilon = 65,000 L mol(-1) cm(-1)). The measured absorbance is directly proportional to EtX(-) concentration present in the sample solutions. The Beer`s law is obeyed in a 1 x 10(-6) to 2 x 10(-4) mol L(-1) concentration range of ethyl xanthate in the pulp with an excellent correlation coefficient (r = 0.999) and a detection limit of 3.1 x 10(-7) mol L(-1), corresponding to 38 mu g L. At flow rates of 200 mu L min(-1) of the donor stream and 100 mu L min(-1) of the acceptor channel a sampling rate of 15 injections per hour could be achieved with RSD < 2.3% (n = 10, 300 mu L injections of 1 x 10(-5) mol L(-1) EtX(-)). Two practical applications demonstrate the versatility of the FIA method: (i) evaluation the free EtX(-) concentration during a laboratory study of the EtX(-) adsorption capacity on pulverized sulfide ore (pyrite) and (ii) monitoring of EtX(-) at different stages (from starting load to washing effluents) of a flotation pilot plant processing a Cu-Zn sulfide ore. (C) 2010 Elsevier By. All rights reserved.

Electronic structure and chemical bonding in W(2) molecule

The electronic structure of the lowest-lying electronic states of W(2) were investigated at the CASPT2 level. The ground state is a X(1)Sigma(+)(g) state, followed by the a(3)Delta(u), b(3)Sigma(+)(u) and A(1)Delta(u) electronic states. Seven low-lying Omega-states were computed: (1)0(g)(+), (2)3(u), (3)2(u), (4)1(u), (5)0(u)(-), (6)1(u), and (7)2(u), with the ground state corresponding to the (1)0(g)(+)(X(1)Sigma(+)(g)) state. Comparison with the other VIB transition metal group dimers indicates a common pattern of electronic structure and spectroscopic properties. (C) 2010 Elsevier B.V. All rights reserved.