The influence of sulfuric environments on concretes elaborated with sulfate resistant cements and mineral admixtures. Part 2: Concrete exposed to Magnesium Sulfate (MgSO4) = Estudio de la influencia de los medios con presencia de sulfatos en hormigones con cementos sulforresistentes y adiciones minerales. Parte 2.Hormigones expuestos a sulfato magnésico (MgSO4)

The present work studies the resistant of the concrete against magnesium sulfate (MgSO4) and compare the results with values obtained previously of the same concretes exposed to sodium sulfate (Na2SO4). Thus, it is possible analyze the influence of the cation type. To that end, four different concrete mixes were made with sulfur resistant cement and mineral admixtures (silica fume, fly ash and blast furnace slag). The concretes were submerged for different period in magnesium sulfate (MgSO4). After that, different tests were carried out to define mechanical and microstructural properties. The results obtained were compared with reference values of concretes cured in calcium hydroxide [Ca(OH)2]. According to the results, the concrete with blast furnace slag presented the best behavior front MgSO4, meanwhile the concretes with silica fume and fly ash were the most susceptible. The resistance of the concrete with blast furnace slag could be attributed to the characteristics of the hydrated silicates formed during the hydration time, which include aluminum in the chemical chain that hinder its chemical decomposition during the attack of magnesium. The magnesium sulfate solution was most aggressive than sodium sulfate solution. El presente trabajo estudia la resistencia de hormigones al ataque de sulfatos provenientes de sulfato magnésico (MgSO4) y compara estos valores con resultados previos de los mismos hormigones atacados con sulfato sódico (Na2SO4). De esta manera se estudia la interacción del catión que acompaña al ion sulfato durante su afectación a la matriz cementicia. Para lo anterior, se diseñaron cuatro dosificaciones empleando cementos sulforresistentes y adiciones minerales (humo de sílice, ceniza volante y escoria de alto horno). Los hormigones se sumergieron, por distintos periodos de tiempo, en disolución de sulfato magnésico (MgSO4) de concentración 1M, para después realizarles ensayos mecánicos y a nivel microestructural. Los valores obtenidos se compararon con los obtenidos en el hormigón de referencia curado en hidróxido cálcico. El hormigón con escoria de alto horno presentó el mejor comportamiento frente a MgSO4, siendo las mezclas de humo de sílice y ceniza volante las más susceptibles. La resistencia del hormigón con escoria se atribuye a las características de los silicatos hidratados formados durante la hidratación, los cuales incorporan aluminio en las cadenas impidiendo su descomposición ante un ataque por magnesio. El medio con sulfato magnésico mostro una mayor agresividad que el medio con sulfato sódico

Phenylpyrrole derivatives as neural and inducible nitric oxide synthase (nNOS and iNOS) inhibitors

Producción CientíficaWe have previously described a series of 3-phenyl-4,5-dihydro-1H-pyrazole derivatives as moderately potent nNOS inhibitors. As a follow up of these studies, several new 5-phenyl-1H-pyrrole-2-carboxamide derivatives have been synthesized, and their biological evaluation as in vitro inhibitors of both neural and inducible Nitric Oxide Synthase (nNOS and iNOS) is described. Some of these compounds show good iNOS/nNOS selectivity and the more potent compounds 5-(2-aminophenyl)-1H-pyrrole-2-carboxilic acid methylamide (QFF205) and cyclopentylamide (QFF212) have been tested as regulators of the in vivo nNOS and iNOS activity. Both compounds prevented the increment of the inducible NOS activity in both cytosol (iNOS) and mitochondria (i-mtNOS) observed in the MPTP model of Parkinson's disease

Pyrazoles and pyrazolines as neural and inducible nitric oxide synthase (nNOS and iNOS) potential inhibitors (III)

Producción CientíficaWe have previously described a series of 4,5-dihydro-1H-pyrazole as moderately potent nNOS inhibitors. As a follow up of these studies, we report here the preparation and the preliminary evaluation of a series of 1-alkyl-3-benzoyl-4,5-dihydro-1H-pyrazole and 1-alkyl-3-benzoyl-1H-pyrazole as potential inhibitors of both neuronal and inducible nitric oxide synthases (nNOS and iNOS). None of the reported compounds exhibited significant iNOS or nNOS inhibition, although the 1-benzyl-3-(2-amino-5-chlorobenzoyl)-1H-pyrazole-5-carboxylic acid ethyl ester derivative (10l), which shows an inhibition of 50% versus iNOS at a 1mM final concentration and no activity against nNOS, is potentially amenable of further optimization. The reasons for the inactivity of the reported series are discussed on the basis of docking studies

The range of the golden-mantle tamarin, Saguinus tripartitus (Milne Edwards, 1878): distributions and sympatry of four tamarin species in Colombia, Ecuador, and northern Peru

A detailed understanding of the range of the golden-mantle tamarin, Saguinus tripartitus (Milne Edwards, 1878), in Amazonian Peru and Ecuador is of particular relevance, not only because it is poorly known but also because it was on the basis of its supposed sympatry with the saddleback tamarin (S. fuscicollis lagonotus) that Thorington (Am J Primatol 15:367–371, 1988) argued that it is a distinct species rather than a saddleback tamarin subspecies, as was believed by Hershkovitz (Living new world monkeys, vol I. The University of Chicago Press, Chicago, 1977). A number of surveys have been carried out since 1988 in the supposed range of S. tripartitus, in both Ecuador and Peru. Here we summarize and discuss these issues and provide a new suggestion for the geographic range of this species; that is, between the ríos Napo and Curaray in Peru and extending east into Ecuador. We also review current evidence for the distributions of Spix’s black-mantle tamarin (S. nigricollis nigricollis), Graells’ black-mantle tamarin (S. n. graellsi), and the saddleback tamarin (S. fuscicollis lagonotus), which are also poorly known, and examine the evidence regarding sympatry between them. We conclude that despite the existence of a number of specimens with collecting localities that indicate overlap in their geographic ranges, the fact that the four tamarin species are of similar size and undoubtedly very similar in their feeding habits militates strongly against the occurrence of sympatry among them

Bioactive imidamide-based compounds targeted against nitric oxide synthase.

The selective inhibition of inducible nitric oxide synthase (iNOS) has become an interesting goal for the treatment of diseases where the immune and inflammatory response of the organism is involved. Septic shock is one prominent example of this type of affections. In this paper, the design and synthesis of twelve substituted pyridinyl- imidamide derivatives is described, together with their biological evaluation as NOS inhibitors. The most potent and selective compound was N-(3-hydroxy-3-(pyridin-3-yl)propyl)acetimidamide 9a (IC50 = 4.6 µM, against iNOS). Pharmacological assays in aortic rat tissue, have confirmed its inhibitory activity on iNOS and the absence of undesired cardicovascular effects. In silico analysis of the most promising compounds (9a, 9b, 9e and 9g) have predicted good drug-likeness properties. Furthermore, they have shown an adequate cell viability. Docking studies carried out on 9a suggest a particular binding mode that involves the essential residue Glu377, and might explain its iNOS selectivity. From a chemical point of view, the article describes an unusual cyclization to obtain pyridinyl-pyrimidine derivatives with high yield

Anticancer activity of novel hybrid molecules containing 5-benzylidene thiazolidine-2,4-dione

Hybridization of two different bioactive molecules with different mechanism of action is one of the methods that are being adopted to treat cancer. Molecules bearing a thiazolidine-2,4-dione scaffold have been recognized as antineoplastic agents with a broad spectrum of activity against many cancer cell lines. In this manuscript we have described the synthesis and biological evaluation of two series of N-3-substituted-5-arylidene thiazolidine-2,4-diones, bearing the α-bromoacryloylamido moiety at the para- or meta-position on the phenyl of the arylidene portion. We have observed that selected compounds 5a, 5c and 5g suppress proliferation of human myeloid leukaemia HL-60 and U937 cells by triggering morphological changes and internucleosomal DNA fragmentation, which are well-known features of apoptosis. Finally, our results indicated that the investigated compounds induced apoptotic cell death through a mechanism that involved activation of multiple caspases and was also associated with the release of cytochrome c from the mitochondria.This work was partially supported by the Ministry of Science and Innovation of Spain and the European Regional Development Fund (SAF2010-21380) and Instituto Canario de Investigación del Cáncer to F.E. Jan Balzarini is funded by GOA (Krediet no. 10/14) of the KU Leuven.Peer Reviewe

Thiadiazoline- and Pyrazoline-Based Carboxamides and Carbothioamides: Synthesis and Inhibition against Nitric Oxide Synthase

Two new families of pyrazoline and thiadiazoline heterocycles have been developed. Their inhibitory activities against two different isoforms of nitric oxide synthase (inducible and neuronal NOS) are reported. The novel derivatives were synthesized combining the arylthiadiazoline or arylpyrazoline skeleton and a carboxamide or carbothioamide moiety, used as starting material ethyl 2-nitrobenzoates or substituted nitrobenzaldehydes, respectively. The structure-activity relationships of final molecules are discussed in terms of the R1 radical effects in the aromatic ring, the Y atom in the heterocyclic system, the X heteroatom in the main chain, and the R2 substituent in the carboxamide or carbothioamide rest. In general, thiadiazolines (5a–e) inhibit preferentially the neuronal isoform; among them, 5a is the best nNOS inhibitor (74.11% at 1 mM, IC50 = 420 μM). In contrast, pyrazolines (6a–r) behave better as iNOS than nNOS inhibitors, 6m being the best molecule of this series (76.86% at 1 mM of iNOS inhibition, IC50 = 130 μM) and the most potent of all tested compounds

Nitrate reductase isozymes in Bradyrhizobium sp. (Lupinus) bacteroids: localisation, biochemical and kinetic characteristics

9 pages, figures, and tables statistics.Bradyrhizobium sp. (Lupinus) strains 750 and IM-43B, possessing nitrate reductase activity (NRA) were used to inoculate Lupinus albus cv. Multolupa plants. Bacteroids from root nodules were sonicated and sedimented to separate membranes from cytosolic fractions. Our results confirmed the existence of constitutive NRA mostly in the membranes, but soluble and membrane-bound NR forms were also induced by nitrate, and both of them used NADH as electron donor. Immunolocalisation of NR using a monoclonal antibody showed the presence of a larger number of epitopes in the soluble region than in membrane of bacteroids, and gold particles increased in those nodules grown with nitrate. Chromatographic purification of NR allowed the detection of two active fractions with an average MW of 91 and 362 kD. A further attempt to separate NR fractions in bacteroids and free-living cells grown with nitrate, led us to detect two more native fractions (180 and 720 kD). SDS-PAGE gel electrophoresis from all of the four native fractions revealed the presence of two common bands of around 20 and 70 kD; these results seem to indicate that all of the native enzymes were associations of one single ≅ 90 kD monomer molecule. Specific NRA increased from the small to the large proteins, suggesting positive cooperation by monomer associations. There was evidence enough to support an interpretation that constitutive and substrate-induced NRs would be formed by a monomeric and its homotetrameric isozyme. On the other hand, three IEF spots were obtained by 2-D gel electrophoresis and by anionic chromatography with pI 7.0, 7.8 and 8.1, when any of the native fractions were analysed. Kinetic studies of the four MW native isoforms showed that the two smallest molecules behaved according to Michaelis-Menten with similar KM, but the 360 and 720 kD fractions fitted much better to straight lines in a Hill plot, indicating allosterism and positive cooperativity.Peer reviewe

Purine derivatives with heterocyclic moieties and related analogues as new antitiumour agents

Identification of new antiproliferative compounds. Four series of compounds were synthesized by the Mitsunobu reaction. Their antiproliferative activity was studied against several cancer cells and a noncancerous fibroblast cell line. Their apoptotic activity was analyzed using a caspase 3/7 fluorescence assay. 9-alkylated-6-halogenated and 2,6-dihalogenated purines show remarkable inhibition of tumor cell proliferation, with the dichloro derivatives being the most potent of all the series. The most promising compound, tetrahydroquinoline 4c, exhibits significant antiproliferative activity against the cancer cells tested, while displaying a 19-fold lower potency against noncancerous fibroblasts, a key feature that indicates potential selectivity against cancer cells. This compound produces a high percentage of apoptosis (58%) after 24 h treatment in human breast cancer MCF-7 cells