Rosuvastatin Reduces Neuroinflammation in the Hemorrhagic Transformation After rt-PA Treatment in a Mouse Model of Experimental Stroke

Hemorrhagic transformation (HT) is a serious complication that stimulates inflammation during reperfusion therapy after acute ischemic stroke. Rosuvastatin, a 3-hydroxymethyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, might improve the outcome of HT by inhibiting neuroinflammation. This study aimed to explore the protective effects of rosuvastatin against HT after recombinant tissue plasminogen activator (rt-PA) treatment in mice with experimental stroke via the attenuation of inflammation. A total of one hundred sixty-nine male BALB/c mice were used in the experiment. HT was successfully established in 70 mice that were subjected to 3 h of middle cerebral artery occlusion (MCAO) followed by a 10 mg/kg rt-PA injection over 10 min and reperfusion for 24 h. The mice were then administered rosuvastatin (1 mg/kg, 5 mg/kg) or saline (vehicle). The brain water content and neurological deficits (wire hang and adhesive removal somatosensory tests) were assessed at 24 h after rt-PA reperfusion following MCAO surgery. The morphology, blood-brain barrier (BBB) permeability and number of astrocytes and microglia were assessed by immunohistochemistry, electron microscopy and western blotting at 24 h after rt-PA reperfusion following MCAO surgery. Rosuvastatin protected against impaired neurological function and reversed the BBB leakage observed in the HT group. The increased activation of astrocytes and microglia and secretion of inflammatory factors caused by HT damage were significantly attenuated by high-dose rosuvastatin treatment vs. normal-dose rosuvastatin treatment. Related inflammatory pathways, such as the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, were downregulated in the rosuvastatin-treated groups compared with the HT group. In conclusion, our results indicate that rosuvastatin is a promising therapeutic agent for HT after rt-PA reperfusion following MCAO surgery in mice, as it attenuates neuroinflammation. Additionally, high-dose rosuvastatin treatment could have a greater anti-inflammatory effect on HT than normal-dose rosuvastatin treatment

DNA prime Listeria boost induces a cellular immune response to SIV antigens in the rhesus macaque model that is capable of limited suppression of SIV239 viral replication

AbstractDNA vaccines and recombinant Listeria monocytogenes that express and secrete SIV Gag and Env antigens were combined in a nonhuman primate prime-boost immunogenicity study followed by a challenge with SIV239. We report that recombinant DNA vaccine delivered intramuscularly, and recombinant L. monocytogenes delivered orally each individually have the ability to induce CD8+ and CD4+ T cell immune responses in a nonhuman primate. Four rhesus monkeys were immunized at weeks 0, 4, 8, and 12 with the pCSIVgag and pCSIVenv DNA plasmids and boosted with SIV expressing L. monocytogenes vaccines at weeks 16, 20, and 28. Four rhesus monkeys received only the L. monocytogenes vaccines at weeks 16, 20, and 28. A final group of monkeys served as a control group. Blood samples were taken before vaccination and 2 weeks post each injection and analyzed by ELISPOT for CD4+ and CD8+ T cell responses. Moderate vaccine induced SIV-specific cellular immune responses were observed following immunization with either DNA or L. monocytogenes vectors. However, the SIV antigen-specific immune responses were significantly increased when Rhesus macaques were primed with SIV DNA vaccines and boosted with the SIV expressing L. monocytogenes vectors. In addition, the combined vaccine was able to impact SIV239 viral replication following an intrarectal challenge. This study demonstrates for the first time that oral L. monocytogenes can induce a cellular immune response in a nonhuman primate and is able to enhance the efficacy of a DNA vaccine as well as provide modest protection against SIV239 challenge

Addition of Amines to a Carbonyl Ligand: Syntheses, Characterization, and Reactivities of Iridium(III) Porphyrin Carbamoyl Complexes

Treatment of (carbonyl)chloro(meso-tetra-p-tolylporphyrinato)iridium(III), (TTP)Ir(CO)Cl (1), with excess primary amines at 23 °C in the presence of Na2CO3 produces the trans-amine-coordinated iridium carbamoyl complexes (TTP)Ir(NH2R)[C(O)NHR] (R = Bn (2a), n-Bu (2b), i-Pr (2c), t-Bu (2d)) with isolated yields up to 94%. The trans-amine ligand is labile and can be replaced with quinuclidine (1-azabicyclo[2.2.2]octane, ABCO), 1-methylimidazole (1-MeIm), triethyl phosphite (P(OEt)3), and dimethylphenylphosphine (PMe2Ph) at 23 °C to afford the hexacoordinated carbamoyl complexes (TTP)Ir(L)[C(O)NHR] (for R = Bn: L = ABCO (3a), 1-MeIm (4a), P(OEt)3 (5a), PMe2Ph (6a)). On the basis of ligand displacement reactions and equilibrium studies, ligand binding strengths to the iridium metal center were found to decrease in the order PMe2Ph \u3e P(OEt)3 \u3e 1-MeIm \u3e ABCO \u3e BnNH2 ≫ Et3N, PCy3. The carbamoyl complexes (TTP)Ir(L)[C(O)NHR] (L = RNH2 (2a,b), 1-MeIm (4a)) undergo protonolysis with HBF4 to give the cationic carbonyl complexes [(TTP)Ir(NH2R)(CO)]BF4 (7a,b) and [(TTP)Ir(1-MeIm)(CO)]BF4 (8), respectively. In contrast, the carbamoyl complexes (TTP)Ir(L)[C(O)NHR] (L = P(OEt)3 (5a), PMe2Ph (6a,c)) reacted with HBF4 to afford the complexes [(TTP)Ir(PMe2Ph)]BF4 (9) and [(TTP)IrP(OEt)3]BF4 (10), respectively. The carbamoyl complexes (TTP)Ir(L)[C(O)NHR] (L = RNH2 (2a–d), 1-MeIm (4a), P(OEt)3 (5b), PMe2Ph (6c)) reacted with methyl iodide to give the iodo complexes (TTP)Ir(L)I (L = RNH2 (11a–d), 1-MeIm (12), P(OEt)3(13), PMe2Ph (14)). Reactions of the complexes [(TTP)Ir(PMe2Ph)]BF4 (9) and [(TTP)IrP(OEt)3]BF4 (10) with [Bu4N]I, benzylamine (BnNH2), and PMe2Ph afforded (TTP)Ir(PMe2Ph)I (14), (TTP)Ir[P(OEt)3]I (13), [(TTP)Ir(PMe2Ph)(NH2Bn)]BF4 (16), and trans-[(TTP)Ir(PMe2Ph)2]BF4 (17), respectively. Metrical details for the molecular structures of 4a and17 are reported

Methyl Complexes of the Transition Metals

Organometallic chemistry can be considered as a wide area of knowledge that combines concepts of classic organic chemistry, that is, based essentially on carbon, with molecular inorganic chemistry, especially with coordination compounds. Transition-metal methyl complexes probably represent the simplest and most fundamental way to view how these two major areas of chemistry combine and merge into novel species with intriguing features in terms of reactivity, structure, and bonding. Citing more than 500 bibliographic references, this review aims to offer a concise view of recent advances in the field of transition-metal complexes containing M-CH fragments. Taking into account the impressive amount of data that are continuously provided by organometallic chemists in this area, this review is mainly focused on results of the last five years. After a panoramic overview on M-CH compounds of Groups 3 to 11, which includes the most recent landmark findings in this area, two further sections are dedicated to methyl-bridged complexes and reactivity.Ministerio de Ciencia e Innovación Projects CTQ2010–15833, CTQ2013-45011 - P and Consolider - Ingenio 2010 CSD2007 - 00006Junta de Andalucía FQM - 119, Projects P09 - FQM - 5117 and FQM - 2126EU 7th Framework Program, Marie Skłodowska - Curie actions C OFUND – Agreement nº 26722

Development of quaternary Fe-based bulk metallic glasses with high saturation magnetization above 1.6 T

were successfully fabricated in Fe–Si–B–P alloy system by copper mold casting. These BMGs exhibit low coercive force of 1.6–1.9 A/m, high effective permeability of 16,500–17,200 and low core loss. In additional, these BMGs exhibit good mechanical properties as well, i.e., high strength of 3200 MPa and plasticity of 1.1%. They are promising to be used as magnetic functional and structural materials in the future

(Co1-xFex)68B21.9Si5.1Nb5 bulk glassy alloys with high glass-forming ability,excellent soft-magnetic properties and superhigh fracture strength

The glass-forming ability (GFA), soft-magnetic properties and mechanical properties of (Co1 x Fex)68B21.9Si5.1Nb5 (x ？ 0.1e0.5) glassy alloys were investigated. The (Co1 xFex)68B21.9Si5.1Nb5 glassy alloys exhibit a wide supercooled liquid region of over 40 K, and high reduced glass transition temperatures between 0.603 and 0.648. As a result, the (Co1 xFex)68B21.9Si5.1Nb5 bulk glassy alloys (BGAs) with diameters up to 5.5 mm were produced by copper mold casting. In addition to high GFA, this Co-based glassy alloys exhibit excellent soft-magnetic properties, i.e., saturation magnetization of 0.49e0.91 T, low coercive force of 0.71e1.58 A/m, and high effective permeability of (2.21e3.25) 104 at 1 kHz under a field of 1 A/m. Besides, this Co-based BGAs also exhibit superhigh fracture strength of 4250e4450 MPa and plastic strain of 0.6e1.3%

Effect of Fe to P concentration ratio on structures, crystallization behavior, and magnetic properties in (Fe0.79+xP0.1-xC0.04B0.04Si0.03)(99)Cu-1 alloys

The effect of Fe to P concentration ratio on structures, crystallization behavior, and magnetic properties in (Fe0.79+xP0.1-xC0.04B0.04Si0.03)(99)Cu-1 alloys was investigated. The increase of Fe to P concentration ratio changes the structure and crystallization process of as-quenched ribbon. Nanocrystalline alloys with excellent soft magnetic properties were synthesized upon annealing the as-quenched ribbon with primary crystals. The (Fe0.84P0.05C0.04B0.04Si0.03)(99)Cu-1 nanocrystalline alloy exhibits excellent magnetic properties, such as high saturation magnetic flux density of 1.74 T, low coercivity of 4.9 A/m, high effective permeability of 22 900 (at 1 kHz), low core loss of 3.1 W/kg at 1.0 T and 400 Hz, and 8.9 W/kg at 1.0 T and 1 kHz, respectively. (C) 2013 AIP Publishing LLC

Enhancement of glass-forming ability of Fe-based bulk metallic glasses with high saturation magnetic flux density

The effects of substituting Fe with Ni on thermal properties, glass-forming ability (GFA) and magnetic properties of Fe76-xNixMo3.5P10C4B4Si2.5 (x=0？30 at.%) alloys were investigated in detail. The breadth of the supercooled liquid region was found to gradually increase from 42 to 55 K with increasing Ni content to 30 at.%. When x=5 at.%, the alloy composition approached a eutectic point, resulting in an increase in GFA. As a result, FeNiMoPCBSi bulkmetallic glasses with critical diameters up to 5.5 mm were successfully synthesized by copper mold casting. These glassy alloys exhibit a high saturation magnetic flux density of 0.75？1.21 T and excellent soft magnetic properties, i.e., low coercive force of 1.1？2.0 A/m, and high effective permeability of 14400？19700 at 1 kHz under a field of 1 A/m. The reasons for the high stability of the supercooled liquid, and the high GFA as well as excellent soft magnetic properties are discussed in this article. Copyright 2012 Author(s). This article is distributed under a Creative Commons Attribution 3.0 Unported Licens