Development and optimization of a new synthetic process for lorcaserin

A two-step process to synthesize racemic lorcaserin was developed from 2-(4-chlorophenyl)ethanol via formation of bromide or tosylate derivatives. These derivatives were reacted with allylamine in neat conditions to provide pure N-(4-chlorophenethyl)allylammonium chloride. This compound was cyclized in neat conditions using aluminum or zinc chloride to give racemic lorcaserin. After resolution of enantiomers, the wrong enantiomer was racemized and recycled to give new R-lorcaserin.     

Ciudadanía activa y personas mayores: viejos conceptos,nuevos abordajes. Una revisión sistemática y metasíntesis cualitativa

The politics of active ageing present active citizenship of the elderly as a key challenge for the coming years. Active citizenship has been defined in different ways (as complimentary in most cases), outlining an eclecticism of participatory activities that includes political engagement in a participatory and deliberative manner, as well as community and voluntary action. This term is found in different contexts such as formal politics, work, civil society, and the home. This paper, based on a systematic review, identifies the context in which this concept emerges in relation to older people and people with dementia. It also analyses the different expressions of active citizenship used, and provides key elements to be taken into account in the formulation of policies in a context of accelerated demographic ageing and where dementia is a public health priority. The notion of active citizenship in old age is a step forward from active ageing to a broader concept that integrates the principle of equality between people irrespective of gender, age and the need for support.     

Nitrosothiol Formation and Protection against Fenton Chemistry by Nitric Oxide-induced Dinitrosyliron Complex Formation from Anoxia-initiated Cellular Chelatable Iron Increase

Dinitrosyliron complexes (DNIC) have been found in a variety of pathological settings associated with ^•NO. However, the iron source of cellular DNIC is unknown. Previous studies on this question using prolonged ^•NO exposure could be misleading due to the movement of intracellular iron among different sources. We here report that brief ^•NO exposure results in only barely detectable DNIC, but levels increase dramatically after 1–2 h of anoxia. This increase is similar quantitatively and temporally with increases in the chelatable iron, and brief ^•NO treatment prevents detection of this anoxia-induced increased chelatable iron by deferoxamine. DNIC formation is so rapid that it is limited by the availability of ^•NO and chelatable iron. We utilize this ability to selectively manipulate cellular chelatable iron levels and provide evidence for two cellular functions of endogenous DNIC formation, protection against anoxia-induced reactive oxygen chemistry from the Fenton reaction and formation by transnitrosation of protein nitrosothiols (RSNO). The levels of RSNO under these high chelatable iron levels are comparable with DNIC levels and suggest that under these conditions, both DNIC and RSNO are the most abundant cellular adducts of ^•NO.     

Expression of manganese superoxide dismutase is not altered in transgenic mice with elevated level of copper-zinc superoxide dismutase

In evaluating the relative expression of copper-zinc and manganese superoxide dismutase (CuZnSOD and MnSOD) in vivo in states like Down syndrome in which one dismutase is present at increased levels, we measured activities of both enzymes, in tissues of control and transgenic mice constitutively expressing increased levels of CuZnSOD, during exposure to normal and elevated oxygen tensions. Using SOD gel electrophoresis assay, CuZnSOD and MnSOD activities of brain, lung, heart, kidney, and liver from mice exposed to either normal (21%) or elevated (>99% oxygen, 630 torr) oxygen tensions for 120 h were compared. Whereas CuZnSOD activity was elevated in tissues of transgenic relative to control mice under both normoxic or hyperoxic conditions, MnSOD activities in organs of transgenic mice were remarkably similar to those of controls under both conditions. To confirm the accuracy of this method in quantitating MnSOD relative to CuZnSOD expression, two other methods were utilized. In lung, which is the organ exposed to the highest oxygen tension during ambient hyperoxia, a sensitive, specific ELISA for MnSOD was used. Again, MnSOD protein was not different in transgenic relative to control mice during exposure to air or hyperoxia. In addition, lung MnSOD protein was not changed significantly by exposure to hyperoxia in either group. In kidney, a mitochondrion-rich organ, SOD assay, before and after inactivation of CuZnSOD with diethyldithiocarbamate, was used. MnSOD activity was not different in organs from air-exposed transgenic relative to control mice. The data indicated that expression of MnSOD in vivo was not affected by overexpression of the CuZnSOD and, therefore, the two enzymes are probably regulated independently.     

The influence of reduced photorespiration on long-term growth and development of wheat

The long-term role of photorespiration was investigated by comparing growth, development, gas exchange characteristics and mineral nutrition of a wheat crop ( Triticum aestivum L. cv. Courtot) cultivated in a culture chamber during a life cycle, either in 4% O₂ or in normal O₂ Low O₂ pressure reduced photorespiration, but CO₂ was controlled so that net photosynthesis remained the same as in the control crop. The growth and development of the low O₂ crop was slowed down. Ear appearance was 16 days late, but the rate of tillering was the same as in the control and was maintained longer so that the final number of tillers was doubled. Pigment, ribulose bisphosphate carboxylase (EC 4.1.1.39) and soluble sugar contents were similar. The response of photosynthesis to CO₂ and O₂ was not appreciably changed by the low O₂ treatment. There was almost no seed formation, and the senescence of the leaves was delayed. It appears that in non-stress conditions most of the photorespiration can be suppressed without damage to the photosynthetic apparatus. Retardation of development and inhibition of reproduction are likely due to other effects of O₂.     

Control of Redox Balance by the Stringent Response Regulatory Protein Promotes Antioxidant Defenses of Salmonella

We report herein a critical role for the stringent response regulatory DnaK suppressor protein (DksA) in the coordination of antioxidant defenses. DksA helps fine-tune the expression of glutathione biosynthetic genes and discrete steps in the pentose phosphate pathway and tricarboxylic acid cycle that are associated with the generation of reducing power. Control of NAD(P)H/NAD(P)⁺ redox balance by DksA fuels downstream antioxidant enzymatic systems in nutritionally starving Salmonella. Conditional expression of the glucose-6-phosphate dehydrogenase-encoding gene zwf, shown here to be under DksA control, increases both the NADPH pool and antioxidant defenses of dksA mutant Salmonella. The DksA-mediated coordination of redox balance boosts the antioxidant defenses of stationary phase bacteria. Not only does DksA increase resistance of Salmonella against hydrogen peroxide (H₂O₂), but it also promotes fitness of this intracellular pathogen when exposed to oxyradicals produced by the NADPH phagocyte oxidase in an acute model of infection. Given the role of DksA in the adjustment of gene expression in most bacteria undergoing nutritional deprivation, our findings raise the possibility that the control of central metabolic pathways by this regulatory protein maintains redox homeostasis essential for antioxidant defenses in phylogenetically diverse bacterial species.     

Rapid mobilization of ferritin iron by ascorbate in the presence of oxygen

L-(—)-ascorbate mobilizes iron from horse-spleen ferritin in the presence of oxygen at pH 8.0. The reaction is strongly stimulated by Cu²⁺. Dehydroascorbate and other stable oxidation products of ascorbate are ineffective. We present evidence that monodehydroascorbate mobilizes ferritin iron by reduction.