Neural and astroglial effects of a chronic parachlorophenylalanine-induced serotonin synthesis inhibition

Serotonin (5HT) is one of the classical neurotransmitters expressed earlier in the embryonic rat brain, and it was proposed as a developmental signal in the central nervous system. In the adult brain, 5HT seems to be involved in neuronal plasticity. It was postulated that S-100 protein, a glial neurotrophic factor, could be modulated by 5HT probably through the glial 5HT1A receptors. In a model of chronic inhibition of endogenous 5HT synthesis produced by the daily administration of parachlorophenylalanine (PCPA) for 2 wk, we have studied by immunohistochemical methods and digital morphometric analysis the expression of two proteins present in rat brain astrocytes: glial fibrillary acidic protein (GFAP) and S-100 protein. The effectiveness of the PCPA treatment was tested by the use of specific anti-5HT antibodies that showed absence of 5HT fibers in 5HT innervation areas like frontal cortex and hippocampus. Different effects of PCPA treatment on serotoninergic raphe nuclei were observed: dorsal raphe nucleus (DRN) seemed to be more sensitive to the PCPA's action than ventral raphe nucleus (VRN). In DRN and in the two 5HT innervation areas studied, glial cells responded to the 5HT depletion induced by PCPA showing astrocytes with large and tortuous processes. Astrocytes from 5HT-depleted regions showed higher immunostaining for S-100 protein than controls. There was not any modification in optical density of S-100 protein immunostaining in VRN, the area less sensitive to PCPA treatment. These observations indicated that astrocytes are sensitive to the 5HT level, and in presence of low 5HT concentration in the intercellular space, astrocytes could react by synthesizing glial proteins like GFAP and S-100 protein.     

Natural Control of Corn Postharvest Fungi Aspergillus flavus and Penicillium sp. Using Essential Oils from Plants Grown in Argentina

The objective in this study was to evaluate the antifungal activity of essential oils from native and commercial aromatic plants grown in Argentina against corn postharvest fungi and to link the essential oil bioactivity with lipid oxidation and morphological changes in fungus cell membrane. Essential oil (EO) of oregano variety Mendocino (OMen), Cordobes (OCor), and Compacto (OCom), mint variety Inglesa (Mi), and Pehaujo (Mp), Suico (Sui); rosemary (Ro), and Aguaribay (Ag) were tested in vitro against 4 corn fungi: A. flavus (CCC116–83 and BXC01), P. oxalicum (083296), and P. minioluteum (BXC03). The minimum fungicidal concentration (MFC) and the minimum inhibitory concentration (MIC) were determined. The chemical profiles of the EOs were analyzed by GC‐MS. Lipid oxidation in cell membrane of fungi was determined by hydroperoxides and related with essential oil antifungal activity. The major compounds were Thymol in OCor (18.66%), Omen (12.18%), and OCom (9.44%); menthol in Mi and Mp; verbenone in Sui; dehydroxy‐isocalamendiol in Ag; and eucaliptol in Ro. OCor, Omen, and OCom showed the best antifungal activity. No antifungal activity was observed in Ag and Ro EO. The hydroperoxide value depended on the fungi (P < 0.001) and the antimicrobial agent (P < 0.001).Membrane lipids were oxidized by Sui EO in A. flavus BXC01 and A. flavus CCC116–83 (0.021 and 0.027 meqO₂/kg, respectively). The results suggest that the EOs of OCor, OMen, OCom, Mi, Mp, and Sui grown in Argentina can be used as natural alternatives to control fungi that produce mycotoxin in maize.     

Reaction of rhodanese with dithiothreitol

The reaction between bovine rhodanese (thiosulfate:cyanide sulfurtransferase, EC 2.8.1.1) and reduced dithiothreitol has been studied. This reagent, in the absence of thiosulfate, reduces the amount of sulfur carried by rhodanese with formation of sulfide and oxidized dithiothreitol: E-S-SH + reduced dithiothreitol replaced by E-SH + HS- + oxidized dithiothreitol, (E = enzyme). An inactivation was observed at high dithiothreitol/enzyme ratios or at very low enzyme concentrations. The inactivation was not observed in the presence of thiosulfate and can be reversed by cyanide or thiosulfate. A thiosulfate reduction activity of rhodanese was also found using dithiothreitol as reductant.     

Antioxidant properties of aminoethylcysteine ketimine decarboxylated dimer: a review

Aminoethylcysteine ketimine decarboxylated dimer is a natural sulfur-containing compound detected in human plasma and urine, in mammalian brain and in many common edible vegetables. Over the past decade many studies have been undertaken to identify its metabolic role. Attention has been focused on its antioxidant properties and on its reactivity against oxygen and nitrogen reactive species. These properties have been studied in different model systems starting from plasma lipoproteins to specific cellular lines. All these studies report that aminoethylcysteine ketimine decarboxylated dimer is able to interact both with reactive oxygen and nitrogen species (hydrogen peroxide, superoxide anion, hydroxyl radical, peroxynitrite and its derivatives). Its antioxidant activity is similar to that of Vitamin E while higher than other hydrophilic antioxidants, such as trolox and N-acetylcysteine.     

Hemisuccinate of 21-hydroxy-6,19-epoxyprogesterone: a tissue-specific modulator of the glucocorticoid receptor

The introduction of a hemisuccinate group at the 21-position of the passive antiglucocorticoid 21OH-6,19OP leads to a compound (21HS-6,19OP) with a notable activity profile toward the glucocorticoid receptor (GR). In contrast to the parent steroid, 21HS-6,19OP behaves as a pure agonist of GR activity in direct transactivation assays. However, the apoptotic effects of 21HS-6,19OP show that the effect depends on cell type: while 21HS-6,19OP is a pure agonist in L929 mouse fibroblasts, in thymocytes 21HS-6,19OP had significant antiglucocorticoid activity. This tissue-specific activity makes 21HS-6,19OP a novel selective GR modulator. To investigate the molecular basis of action of 21HS-6,19OP, we carried out molecular dynamics simulations (6 ns) of the GR ligand binding domain (LBD) complexed with 21HS-6,19OP. Our results indicate that the hemisuccinate moiety may play a key role in stabilizing the active conformation of the receptor dimerization interface, reverting the changes observed with the antagonist 21OH-6,19OP. Other changes in regions of the GR related to cofactor recruitment (possibly tissue-specific), could explain this particular activity profile.     

Scalable Pareto set generation for multiobjective co-design problems in water distribution networks: a continuous relaxation approach

In this paper, we study the multiobjective co-design problem of optimal valve placement and operation in water distribution networks, addressing the minimization of average pressure and pressure variability indices. The presented formulation considers nodal pressures, pipe flows and valve locations as decision variables, where binary variables are used to model the placement of control valves. The resulting optimization problem is a multiobjective mixed integer nonlinear optimization problem. As conflicting objectives, average zone pressure and pressure variability can not be simultaneously optimized. Therefore, we present the concept of Pareto optima sets to investigate the trade-offs between the two conflicting objectives and evaluate the best compromise. We focus on the approximation of the Pareto front, the image of the Pareto optima set through the objective functions, using the weighted sum, normal boundary intersection and normalized normal constraint scalarization techniques. Each of the three methods relies on the solution of a series of single-objective optimization problems, which are mixed integer nonlinear programs (MINLPs) in our case. For the solution of each single-objective optimization problem, we implement a relaxation method that solves a sequence of nonlinear programs (NLPs) whose stationary points converge to a stationary point of the original MINLP. The relaxed NLPs have a sparse structure that come from the sparse water network graph constraints. In solving the large number of relaxed NLPs, sparsity is exploited by tailored techniques to improve the performance of the algorithms further and render the approaches scalable for large scale networks. The features of the proposed scalarization approaches are evaluated using a published benchmarking network model.     

Antioxidant properties of the decarboxylated dimer of aminoethylcysteine ketimine: assessment of its ability to scavenge peroxynitrite

In the present study we used an in-vitro technique to examine initiation and propagation of blood coagulation at the surface of tantalum coronary stents exposed to flowing platelet-rich and platelet-free plasma. The time course of factor IXa production at the surface of the stent was not influenced by platelets. In spite of a significant factor IXa production, no thrombin activity was detected when the tantalum stent was exposed to platelet-free plasma; only when the stent was exposed to platelet-rich plasma was extensive thrombin production observed. These findings indicate that tantalum triggers blood coagulation, but that (adherent) platelets are essential for thrombin generation. Heparin-coated tantalum stents exposed to flowing platelet-rich plasma showed that factor IXa generation was slightly reduced compared with the bare stent. However, the heparin coating drastically delayed the onset of thrombin generation and largely reduced the steady-state production of thrombin. We found a clear relationship between the antithrombin binding capacity and the antithrombogenic potential of the heparin-coated stents. The mode of action of immobilized heparin is thought to abrogate thrombin generation by inhibiting thrombin-dependent positive feedback reactions at the surface of the coronary stent.     

Prior Assumptions for Leak Localisation in Water Distribution Networks with Uncertainties

Water Resources Management - Hydraulic model-based leak (burst) localisation in water distribution networks is a challenging problem due to a limited number of hydraulic measurements, a wide range...