Effects of Venlafaxine,Risperidone and Febuxostat on Cuprizone-Induced Demyelination,Behavioral Deficits and Oxidative Stress

Multiple sclerosis (MS) is a demyelinating, autoimmune disease that affects a large number of young adults. Novel therapies for MS are needed considering the efficiency and safety limitations of current treatments. In our study, we investigated the effects of venlafaxine (antidepressant, serotonin-norepinephrine reuptake inhibitor), risperidone (atypical antipsychotic) and febuxostat (gout medication, xanthine oxidase inhibitor) in the cuprizone mouse model of acute demyelination, hypothesizing an antagonistic effect on TRPA1 calcium channels. Cuprizone and drugs were administered to C57BL6/J mice for five weeks and locomotor activity, motor performance and cold sensitivity were assessed. Mice brains were harvested for histological staining and assessment of oxidative stress markers. Febuxostat and metabolites of venlafaxine (desvenlafaxine) and risperidone (paliperidone) were tested for TRPA1 antagonistic activity. Following treatment, venlafaxine and risperidone significantly improved motor performance and sensitivity to a cold stimulus. All administered drugs ameliorated the cuprizone-induced deficit of superoxide dismutase activity. Desvenlafaxine and paliperidone showed no activity on TRPA1, while febuxostat exhibited agonistic activity at high concentrations. Our findings indicated that all three drugs offered some protection against the effects of cuprizone-induced demyelination. The agonistic activity of febuxostat can be of potential use for discovering novel TRPA1 ligands.     

Sustainable treatment of wastewaters resulted in the textile dyeing industry

Adsorption on fly-ash-based substrates is discussed as a possible alternative to the industrial processes used for the treatment of wastewaters resulted in the dyeing industry. Three samples, containing four dyes and one conditioner, were collected from the dyeing and rinsing baths in a textile company. Adsorption on fly ash was comparatively discussed with adsorption and photocatalysis, both on fly ash and a mixed suspension with TiO₂. The fly-ash crystalline substrates are characterized by X-ray diffraction (XRD) and morphology studies were done using atomic force microscopy. The wastewater, before and after treatment is characterized by quality indicators (pH, TDS, BOD₅, COD, TOC, color, and total chromium content). The studies allow to calculate the efficiency of the dyes removal process and the kinetic parameters, for the pseudo-second order mechanism. The results show that, in designing an industrial wastewater treatment process, the results obtained in the investigations on single-dye solutions must be completed with data specifically obtained on industrial wastewaters. The data also support the assumption of competitive adsorption, between the initial components and between these and the possible by-products resulted after photocatalysis.     

On the Tactile Sensing Based on the Smart Materials

A flexible finger with muscles made of Nitinol wires and the skin made of auxetic material is analyzed from the tactile sensing point of view. The recognizing of the shape and texture of 3D objects is performed by simulation the action of an array of nanopiezotronic transistors integrated into the skin. The array of nanopiezotronic transistors makes possible the detection of the pressure-induced changes in the auxetic skin. The shape and texture of the objects is best estimated by determining the surface and texture as an n-ellipsoid defined by 12 parameters. An inverse problem is solved in order to find these parameters from the condition that the n-ellipsoid best fits the set of data points probed by touch with the finger.     

Graphene–Oxide Porous Biopolymer Hybrids Enhance In Vitro Osteogenic Differentiation and Promote Ectopic Osteogenesis In Vivo

Over the years, natural-based scaffolds have presented impressive results for bone tissue engineering (BTE) application. Further, outstanding interactions have been observed during the interaction of graphene oxide (GO)-reinforced biomaterials with both specific cell cultures and injured bone during in vivo experimental conditions. This research hereby addresses the potential of fish gelatin/chitosan (GCs) hybrids reinforced with GO to support in vitro osteogenic differentiation and, further, to investigate its behavior when implanted ectopically. Standard GCs formulation was referenced against genipin (Gp) crosslinked blend and 0.5 wt.% additivated GO composite (GCsGp/GO 0.5 wt.%). Pre-osteoblasts were put in contact with these composites and induced to differentiate in vitro towards mature osteoblasts for 28 days. Specific bone makers were investigated by qPCR and immunolabeling. Next, CD1 mice models were used to assess de novo osteogenic potential by ectopic implantation in the subcutaneous dorsum pocket of the animals. After 4 weeks, alkaline phosphate (ALP) and calcium deposits together with collagen synthesis were investigated by biochemical analysis and histology, respectively. Further, ex vivo materials were studied after surgery regarding biomineralization and morphological changes by means of qualitative and quantitative methods. Furthermore, X-ray diffraction and Fourier-transform infrared spectroscopy underlined the newly fashioned material structuration by virtue of mineralized extracellular matrix. Specific bone markers determination stressed the osteogenic phenotype of the cells populating the material in vitro and successfully differentiated towards mature bone cells. In vivo results of specific histological staining assays highlighted collagen formation and calcium deposits, which were further validated by micro-CT. It was observed that the addition of 0.5 wt.% GO had an overall significant positive effect on both in vitro differentiation and in vivo bone cell recruitment in the subcutaneous region. These data support the GO bioactivity in osteogenesis mechanisms as being self-sufficient to elevate osteoblast differentiation and bone formation in ectopic sites while lacking the most common osteoinductive agents.     

Angiotensin II Stimulation of DPP4 Activity Regulates Megalin in the Proximal Tubules

Proteinuria is a marker of incipient kidney injury in many disorders, including obesity. Previously, we demonstrated that megalin, a receptor endocytotic protein in the proximal tubule, is downregulated in obese mice, which was prevented by inhibition of dipeptidyl protease 4 (DPP4). Obesity is thought to be associated with upregulation of intra-renal angiotensin II (Ang II) signaling via the Ang II Type 1 receptor (AT₁R) and Ang II suppresses megalin expression in proximal tubule cells in vitro. Therefore, we tested the hypothesis that Ang II will suppress megalin protein via activation of DPP4. We used Ang II (200 ng/kg/min) infusion in mice and Ang II (10⁻⁸ M) treatment of T35OK-AT₁R proximal tubule cells to test our hypothesis. Ang II-infused mouse kidneys displayed increases in DPP4 activity and decreases in megalin. In proximal tubule cells, Ang II stimulated DPP4 activity concurrent with suppression of megalin. MK0626, a DPP4 inhibitor, partially restored megalin expression similar to U0126, a mitogen activated protein kinase (MAPK)/extracellular regulated kinase (ERK) kinase kinase (MEK) 1/2 inhibitor and AG1478, an epidermal growth factor receptor (EGFR) inhibitor. Similarly, Ang II-induced ERK phosphorylation was suppressed with MK0626 and Ang II-induced DPP4 activity was suppressed by U0126. Therefore, our study reveals a cross talk between AT₁R signaling and DPP4 activation in the regulation of megalin and underscores the significance of targeting DPP4 in the prevention of obesity related kidney injury progression.     

Ammonia two-phase flow in a horizontal smooth tube: Flow pattern observations,diabatic and adiabatic frictional pressure drops and assessment of prediction methods

The present study illustrates new experimental two-phase flow pattern observations together with diabatic boiling and adiabatic two-phase frictional pressure drop results for ammonia (R717) flowing inside a 14-mm internal diameter, smooth horizontal stainless steel tube. The flow pattern observations were made for mass velocities of 50, 100 and 160 kg s^?1 m^?2 and saturation temperatures of ?14, ?2 and 12 °C for vapor qualities ranging from 0.05 to 0.6. The flow patterns observed during the study included: stratified-wavy, slug-stratified-wavy, slug, intermittent and annular. For all the experimental conditions, the flow structure observations were compared against the predictions of the flow pattern map model of Wojtan et al. [L. Wojtan, T. Ursenbacher, J.R. Thome, Investigation of flow boiling in horizontal tubes: part I – a new diabatic two-phase flow pattern map, Int. J. Heat Mass Transfer 48 (2005) 2955–2969] and showed very good correspondence. The frictional pressure drop measurements were obtained for vapor qualities from 0.05 to 0.6, saturation temperatures from ?14 to 14 °C, mass velocities from 50 to 160 kg s^?1 m^?2 and heat fluxes from 12 to 25 kW m^?2. The experimental results show the traditional pressure drop trends: the frictional pressure drop increases with vapor quality and mass velocity. Moreover, the results also show that both diabatic and adiabatic frictional pressure drop values are similar, that is, the boiling process in itself does not affect the frictional pressure drop. The correlations of Friedel [L. Friedel, Improved friction drop correlations for horizontal and vertical two-phase pipe flow, in: European Two-Phase Flow Group Meeting, paper E2, Ispra, Italy, 1979], Lockhart and Martinelli [R.W. Lockhart, R.C. Martinelli, Proposed correlation of data for isothermal two-phase two-component in pipes, Chem. Eng. Process 45 (1949) 39–48] and Müller-Steinhagen and Heck [H. Müller-Steinhagen, K. Heck, A simple friction pressure correlation for two-phase flow in pipes, Chem. Eng. Process 20 (1986) 297–308] predicted only 54%, 52% and 60% of the experimental data within ±30%, respectively. The correlation of Grönnerud [R. Grönnerud, Investigation of liquid hold-up, flow-resistance and heat transfer in circulation type of evaporators, part iv: two-phase flow resistance in boiling refrigerans, in: Annexe 1972-1, Bull. de l’Inst. Froid, 1979] predicted 93% of the data and the flow pattern based method of Moreno Quibén and Thome [J. Moreno Quibén, J.R. Thome, Flow pattern based two-phase frictional pressure drop model for horizontal tubes. Part II: new phenomenological model, Int. J. Heat Fluid Flow 28 (2007) 1060–1072] predicted more than 97% of the experimental data within the same error band, while the latter method captures almost 89% of the data within ±20%.     

Membrane bioreactors in industrial wastewater treatment--European experiences, examples and trends.

In wastewater treatment, micro- and ultra-filtration membranes are used for the separation of the activated sludge (biomass) from the treated water. This offers the advantages of a complete removal of solids and bacteria, as well as most of the viruses, namely those attached to the suspended solids. Compared to the conventional activated sludge process (CAS) this technology allows a much higher biomass concentration (MLSS) whereby the reactor volume and the footprint decreases. With increasing MLSS, the viscosity of the sludge increases, which leads to reduced oxygen transfer rates. Depending on the type of membrane and membrane module, the pre-treatment has to be more sophisticated to prevent clogging and sludging of the modules. Due to fouling and scaling, the flux through the membranes will decrease with time. The decrease depends on the water quality as well as on the measurements taken to minimize fouling. Mainly, three strategies are available: lowering the flux, increasing the "crossflow" and cleaning of the membranes. Different strategies including backwash and chemical cleaning "in situ", "on air" and "ex situ" can be applied. It has been proven more effective to apply preventive regular cleaning. Besides the energy demand for oxygen supply--which is typically in the range of 0.3 kWh/m3 for municipal wastewater--the energy for fouling prevention is substantial. Immersed membranes need approximately 0.4 to 1 kWh/m3 for the coarse bubble aeration, whereas tubular modules require 1 to 4 kWh/m3 pump energy. For proper design of industrial wastewater treatment, the verification of applicability and the development of adequate cleaning strategies, it is a precondition to run pilot tests for a sufficient period of time with the wastewater to be treated. More than 100 industrial wastewater treatment membrane bioreactors (MBR) are in operation in Europe. Data of three case studies for a sewage sludge dewatering plant in UK (12,000 m3/d), a plant for the treatment of pharmaceutical wastewater in Germany (3600 m3/d), as well for revamping of an chemical WWTP >2000 m3/d in Italy, are given. MBRs will be used in future wherever high quality effluent is required, because of a sensitive receiving water body or due to the fact of water reuse as process water. MBRs are a perfect pre-treatment in industrial applications when further treatment with nanofiltration or reverse osmosis is considered. The technique is advanced and can be applied both in municipal and industrial wastewater treatment. Higher operational costs must be balanced by superior effluent quality.     

Effect of dry fractionated hybrid protein ingredients on the structural,textural, thermal and sensory properties of gluten-free oat and faba pasta

Protein-enriched gluten-free pasta was prepared from oat starch-rich endosperm (SRE), which was substituted with different proportions of oat protein concentrate (OPC) and/or faba protein concentrate (FPC) fractions in order to obtain a similar protein content (18% and 35%). Accordingly, the health claims ‘source of protein’ and ‘high protein’ were achieved. Pasta with OPC and FPC had lower optimal cooking time (8 and 6.3 min), cooking loss (6% and 10.2% dm) and water absorption (152% and 147%) than control SRE pasta (9.3 min; 12.3% dm and 185%). Addition of protein concentrates produced an increase in hardness and chewiness of spaghetti. The glycaemic index of pasta was lowered by the addition of protein ingredients, the lowest value being achieved with FPC. In vitro protein digestibility of pasta increased up to 3.5% for OPC and up to 7.1% in case of FPC addition. The most protein-digestible pasta was that with FPC addition to reach 35% protein content.