Search results for: polylactic acid particles
Commenced in January 2007
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Paper Count: 4823

Search results for: polylactic acid particles

263 Vitex agnus-castus Anti-Inflammatory, Antioxidants Characters and Anti-Tumor Effect in Ehrlich Ascites Carcinoma Model

Authors: Abeer Y. Ibrahim, Faten M. Ibrahim, Samah A. El-Newary, Saber F. Hendawy

Abstract:

Objective: Appreciation of in-vitro anti-inflammatory and antioxidant characters of Vitex agnus-castus berries alcoholic extract and fractions, as well as in-vivo antitumor ability of alcoholic extract and chloroform fraction against Ehrlich ascites carcinoma is the aim of this study. Material and methods: Antioxidant properties of crude alcoholic extract of vitex berries as well as petroleum ether, chloroform, ethyl acetate and butanol fractions were evaluated, in-vitro assessments, as compared with standard materials, l-ascorbic acid (vitamin C) and butylated hydroxyl toluene(BHT). The anti-inflammatory activity was investigated in cyclooxygenase (COX)-1 and COX-2 inhibition assays. Moreover, in-vivo antitumor effect of vitex berries alcoholic and chloroform extracts were evaluated using Ehrlich ascites carcinoma model. Data were presented as mean±SE, and data were analyzed by one-way analysis of variance test. Results and conclusion: Berries crude extract showed potent antioxidant activity followed with its fractions ethyl acetate and chloroform as compared with standard (V.C and BHT). Ethyl acetate fraction showed good reduction capability, metal ion chelation, hydrogen peroxide scavenging, nitric oxide scavenging and superoxide anion scavenging. Meanwhile, chloroform fraction produced the highest free radical scavenging activity and total antioxidant capacity. In respectable of lipid peroxidation inhibition, crude alcoholic extract and its fractions cleared weak inhibition in comparing with standard materials. Anti-inflammatory activity of V. agnus-castus berries chloroform fraction of vitex was best COX-2 inhibitor (IC₅₀, 135.41 µg/ ml) as compared to vitex alcoholic extract or ethyl acetate fraction with weak inhibitory effect on COX-1 (IC50, 778.432 µg/ ml), where the lowest effect on COX-1 was recorded with alcoholic extract. Alcoholic extract and its fractions showed weak COX-1 inhibition activity, whereas COX-2 was inhibited (100%), compared with celecoxib drug (72% at 1000ppm). The crude alcoholic and chloroform extracts of V. agnus-castus barries significantly reduced the viable Ehrlich cell count and increased nonviable count with amelioration of all hematological parameters. This amelioration was reflected on increasing median survival time and significant increase (P < 0.05) in lifespan.

Keywords: anti-inflammatory, antioxidants, ehrlich ascites carcinoma, Vitex agnus-castus

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262 Diselenide-Linked Redox Stimuli-Responsive Methoxy Poly(Ethylene Glycol)-b-Poly(Lactide-Co-Glycolide) Micelles for the Delivery of Doxorubicin in Cancer Cells

Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

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The recent advancements in synthetic chemistry and nanotechnology fostered the development of different nanocarriers for enhanced intracellular delivery of pharmaceutical agents to tumor cells. Polymeric micelles (PMs), characterized by small size, appreciable drug loading capacity (DLC), better accumulation in tumor tissue via enhanced permeability and retention (EPR) effect, and the ability to avoid detection and subsequent clearance by the mononuclear phagocyte (MNP) system, are convenient to improve the poor solubility, slow absorption and non-selective biodistribution of payloads embedded in their hydrophobic cores and hence, enhance the therapeutic efficacy of chemotherapeutic agents. Recently, redox-responsive polymeric micelles have gained significant attention for the delivery and controlled release of anticancer drugs in tumor cells. In this study, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA, and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. The successful synthesis of the copolymers was verified by different spectroscopic techniques. Above the critical micelle concentration, the amphiphilic copolymer, Bi(mPEG-PLGA)-Se₂, self-assembled into stable micelles. The DLS data indicated that the hydrodynamic diameter of the micelles (123.9 ± 0.85 nm) was suitable for extravasation into the tumor cells through the EPR effect. The drug loading content (DLC) and encapsulation efficiency (EE) of DOX-loaded micelles were found to be 6.61 wt% and 54.9%, respectively. The DOX-loaded micelles showed initial burst release accompanied by sustained release trend where 73.94% and 69.54% of encapsulated DOX was released upon treatment with 6mM GSH and 0.1% H₂O₂, respectively. The biocompatible nature of Bi(mPEG-PLGA)-Se₂ copolymer was confirmed by the cell viability study. In addition, the DOX-loaded micelles exhibited significant inhibition against HeLa cells (44.46%), at a maximum dose of 7.5 µg/mL. The fluorescent microscope images of HeLa cells treated with 3 µg/mL (equivalent DOX concentration) revealed efficient internalization and accumulation of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles in the cytosol of cancer cells. In conclusion, the intelligent, biocompatible, and the redox stimuli-responsive behavior of Bi(mPEG-PLGA)-Se₂ copolymer marked the potential applications of diselenide-linked mPEG-PLGA micelles for the delivery and on-demand release of chemotherapeutic agents in cancer cells.

Keywords: anticancer drug delivery, diselenide bond, polymeric micelles, redox-responsive

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261 Development of Extruded Prawn Snack Using Prawn Flavor Powder from Prawn Head Waste

Authors: S. K. Sharma, P. Kumar, Pratibha Singh

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Consumption of SNACK is growing its popularity every day in India and a broad range of these items are available in the market. The end user interest in ready-to-eat snack foods is constantly growing mainly due to their ease, ample accessibility, appearance, taste and texture. Food extrusion has been practiced for over fifty years. Its role was initially limited to mixing and forming cereal products. Although thermoplastic extrusion has been successful for starch products, extrusion of proteins has achieved only limited success. In this study, value-added extruded prawn product was prepared with prawn flavor powder and corn flour using a twin-screw extruder. Prawn flavor concentrates prepared from fresh prawn head (Solenocera indica). To prepare flavor concentrate prawn head washed with potable water and blended with 200ml 3% salt solution per 250gm head weight to make the slurry, which was further put in muslin cloth and boiled with salt and starch solution for 10 minutes, cooled to room temperature and filtered, starch added to the filtrate and made into powder in an electrically drier at 43-450c. The mixture was passed through the twin-screw extruder (co-rotating twin screw extruder - basic technology Pvt. Ltd., Kolkata) which was operated at a particular speed of rotation, die diameter, temperature, moisture, and fish powder concentration. Many trial runs were conducted to set up the process variables. The different extrudes produced after each trail were examined for the quality and characteristics. The effect of temperature, moisture, screw speed, protein, fat, ash and thiobarbituric acid (TBA) number and expansion ratio were studied. In all the four trials, moisture, temperature, speed and die diameter used was 20%, 100°C, 350 rpm and 4 mm, respectively. The ratio of prawn powder and cornstarch used in different trials ranged between 2:98 and 10:90. The storage characteristics of the final product were studied using three different types of packaging under nitrogen flushing, i.e. a- 12-pm polyester, 12-pm metalized polyester, 60-11m polyethylene (metalized polyester a), b- 12-11m metalized polyester, 37.5-11m polyethylene (metalized polyester b), c- 12-11m polyethylene, 9-11m aluminium foil, 37.5-11m polyethylene (aluminium foil). The organoleptic analysis was carried out on a 9-point hedonic scale. The study revealed that the fried product packed in aluminum foil under nitrogen flushing would remain acceptable for more than three months.

Keywords: extruded product, prawn flavor, twin-screw extruder, storage characteristics

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260 Boiler Ash as a Reducer of Formaldehyde Emission in Medium-Density Fiberboard

Authors: Alexsandro Bayestorff da Cunha, Dpebora Caline de Mello, Camila Alves Corrêa

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In the production of fiberboards, an adhesive based on urea-formaldehyde resin is used, which has the advantages of low cost, homogeneity of distribution, solubility in water, high reactivity in an acid medium, and high adhesion to wood. On the other hand, as a disadvantage, there is low resistance to humidity and the release of formaldehyde. The objective of the study was to determine the viability of adding industrial boiler ash to the urea formaldehyde-based adhesive for the production of medium-density fiberboard. The raw material used was composed of Pinus spp fibers, urea-formaldehyde resin, paraffin emulsion, ammonium sulfate, and boiler ash. The experimental plan, consisting of 8 treatments, was completely randomized with a factorial arrangement, with 0%, 1%, 3%, and 5% ash added to the adhesive, with and without the application of a catalyst. In each treatment, 4 panels were produced with density of 750 kg.m⁻³, dimensions of 40 x 40 x 1,5 cm, 12% urea formaldehyde resin, 1% paraffin emulsion and hot pressing at a temperature of 180ºC, the pressure of 40 kgf/cm⁻² for a time of 10 minutes. The different compositions of the adhesive were characterized in terms of viscosity, pH, gel time and solids, and the panels by physical and mechanical properties, in addition to evaluation using the IMAL DPX300 X-ray densitometer and formaldehyde emission by the perforator method. The results showed a significant reduction of all adhesive properties with the use of the catalyst, regardless of the treatment; while the percentage increase of ashes provided an increase in the average values of viscosity, gel time, and solids and a reduction in pH for the panels with a catalyst; for panels without catalyst, the behavior was the opposite, with the exception of solids. For the physical properties, the results of the variables of density, compaction ratio, and thickness were equivalent and in accordance with the standard, while the moisture content was significantly reduced with the use of the catalyst but without the influence of the percentage of ash. The density profile for all treatments was characteristic of medium-density fiberboard, with more compacted and dense surfaces when compared to the central layer. For thickness, the swelling was not influenced by the catalyst and the use of ash, presenting average values within the normalized parameters. For mechanical properties, the influence of ashes on the adhesive was negatively observed in the modulus of rupture from 1% and in the traction test from 3%; however, only this last property, in the percentages of 3% and 5%, were below the minimum limit of the norm. The use of catalyst and ashes with percentages of 3% and 5% reduced the formaldehyde emission of the panels; however, only the panels that used adhesive with catalyst presented emissions below 8mg of formaldehyde / 100g of the panel. In this way, it can be said that boiler ash can be added to the adhesive with a catalyst without impairing the technological properties by up to 1%.

Keywords: reconstituted wood panels, formaldehyde emission, technological properties of panels, perforator

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259 Identification of Peroxisome Proliferator-Activated Receptors α/γ Dual Agonists for Treatment of Metabolic Disorders, Insilico Screening, and Molecular Dynamics Simulation

Authors: Virendra Nath, Vipin Kumar

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Background: TypeII Diabetes mellitus is a foremost health problem worldwide, predisposing to increased mortality and morbidity. Undesirable effects of the current medications have prompted the researcher to develop more potential drug(s) against the disease. The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptors family and take part in a vital role in the regulation of metabolic equilibrium. They can induce or repress genes associated with adipogenesis, lipid, and glucose metabolism. Aims: Investigation of PPARα/γ agonistic hits were screened by hierarchical virtual screening followed by molecular dynamics simulation and knowledge-based structure-activity relation (SAR) analysis using approved PPAR α/γ dual agonist. Methods: The PPARα/γ agonistic activity of compounds was searched by using Maestro through structure-based virtual screening and molecular dynamics (MD) simulation application. Virtual screening of nuclear-receptor ligands was done, and the binding modes with protein-ligand interactions of newer entity(s) were investigated. Further, binding energy prediction, Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit along with the structural comparative analysis of approved PPARα/γ agonists with screened hit was done for knowledge-based SAR. Results and Discussion: The silicone chip-based approach recognized the most capable nine hits and had better predictive binding energy as compared to the reference drug compound (Tesaglitazar). In this study, the key amino acid residues of binding pockets of both targets PPARα/γ were acknowledged as essential and were found to be associated in the key interactions with the most potential dual hit (ChemDiv-3269-0443). Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit and found root mean square deviation (RMSD) stabile around 2Å and 2.1Å, respectively. Frequency distribution data also revealed that the key residues of both proteins showed maximum contacts with a potent hit during the MD simulation of 20 nanoseconds (ns). The knowledge-based SAR studies of PPARα/γ agonists were studied using 2D structures of approved drugs like aleglitazar, tesaglitazar, etc. for successful designing and synthesis of compounds PPARγ agonistic candidates with anti-hyperlipidimic potential.

Keywords: computational, diabetes, PPAR, simulation

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258 Feeding Effects of Increasing Levels of Yerba Mate on Lamb Meat Quality

Authors: Yuli Andrea P. Bermudez, Richard R. Lobo, Tamyres R. D. Amorim, Danny Alexander R. Moreno, Angelica Simone C. Pereira, Ives Claudio D. Bueno

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The use of natural antioxidants in animal feed can positively modify the profile of fatty acids (FAs) in meat, due to the presence of secondary metabolites, mainly phenolic and flavonoid compounds, which promote an increase in the associated polyunsaturated fatty acids (PUFA) with beneficial factors in human health. The goal of this study was to evaluate the effect of the dietary inclusion percentage of yerba mate extract (Ilex paraguariensis St. Hilaire) as a natural antioxidant on lamb meat quality. The animals were confined for 53 days and fed with corn silage and concentrated in the proportion of 60:40, respectively, were divided into four homogeneous groups (n = 9 lambs/group), to each of the treatments, one control group without yerba mate extract - YME (0%) and three treatments with 1, 2 and 4% the inclusion of YME on a DM basis. Samples of the Longissimus thoracis (LT) muscle were collected from the deboning of 36 lambs, analyzing pH values, color parameters (brightness: L*, red value: a*, and yellow: b*), fatty acid profile, total lipids, and sensory analysis. The inclusion of YME modified the value of b* (P = 0.0041), indicating a higher value of yellow color in the meat, for the group supplemented with 4% YME. All data were statistically evaluated using the MIXED procedure of the statistical package SAS 9.4. However, it did not show differences in the final live weight in the groups evaluated, as well as in the pH values (P = 0.1923) and the total lipid concentration (P = 0.0752). The FAs (P ≥ 0.1360) and health indexes were not altered by the inclusion of YME (P ≥ 0.1360); only branched-chain fatty acids (BCFA) exhibited a diet effect (P = 0.0092) in the group that had 4% of the extract. In the sensory analysis test with a hedonic scale it did not show differences between the treatments (P ≥ 0.1251). Nevertheless, in the just about-right test, using (note 1) to 'very strong, softness or moist' (note 5); the softness was different between the evaluated treatments (P = 0.0088) where groups with 2% YME had a better acceptance of tasters (4.15 ± 0.08) compared to the control (3.89 ± 0.08). In conclusion, although the addition of YME has shown positive results in sensory acceptance and in increasing the concentration of BCFA, fatty acids beneficial to human health, without changing the physical-chemical parameters in lamb meat, the absolute changes are considered to have been quite small, which was probably related to the high efficiency of PUFA biohydrogenation in the n the rumen.

Keywords: composition, health, antioxidant, meat analysis

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257 A New Second Tier Screening for Congenital Adrenal Hyperplasia Utilizing One Dried Blood Spot

Authors: Engy Shokry, Giancarlo La Marca, Maria Luisa Della Bona

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Newborn screening for Congenital Adrenal Hyperplasia (CAH) relies on quantification of 17α-hydroxyprogesterone using enzyme immunoassays. These assays, in spite of being rapid, readily available and easy to perform, its reliability was found questionable due to lack of selectivity and specificity resulting in large number of false-positives, consequently family anxiety and associated hospitalization costs. To improve specificity of conventional 17α-hydroxyprogesterone screening which may experience false transient elevation in preterm, low birth weight or acutely ill neonates, steroid profiling by LC-MS/MS as a second-tier test was implemented. Unlike the previously applied LC-MS/MS methods, with the disadvantage of requiring a relatively high number of blood drops. Since newborn screening tests are increasing, it is necessary to minimize the sample volume requirement to make the maximum use of blood samples collected on filter paper. The proposed new method requires just one 3.2 mm dried blood spot (DBS) punch. Extraction was done using methanol: water: formic acid (90:10:0.1, v/v/v) containing deuterium labelled internal standards. Extracts were evaporated and reconstituted in 10 % acetone in water. Column switching strategy for on-line sample clean-up was applied to improve the chromatographic run. The first separative step retained the investigated steroids and passed through the majority of high molecular weight impurities. After the valve switching, the investigated steroids are back flushed from the POROS® column onto the analytical column and separated using gradient elution. Found quantitation limits were 5, 10 and 50 nmol/L for 17α-hydroxyprogesterone, androstenedione and cortisol respectively with mean recoveries of between 98.31-103.24 % and intra-/ inter-assay CV% < 10 % except at LLOQ. The method was validated using standard addition calibration and isotope dilution strategies. Reference ranges were determined by analysing samples from 896 infants of various ages at the time of sample collection. The method was also applied on patients with confirmed CAH. Our method represents an attractive combination of low sample volume requirement, minimal sample preparation time without derivatization and quick chromatography (5 min). The three steroid profile and the concentration ratios (17OHP + androstenedione/cortisol) allowed better screening outcomes of CAH reducing false positives, associated costs and anxiety.

Keywords: congenital adrenal hyperplasia (CAH), 17α-hydroxyprogesterone, androstenedione, cortisol, LC-MS/MS

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256 Hydrogeophysical Investigations And Mapping of Ingress Channels Along The Blesbokspruit Stream In The East Rand Basin Of The Witwatersrand, South Africa

Authors: Melvin Sethobya, Sithule Xanga, Sechaba Lenong, Lunga Nolakana, Gbenga Adesola

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Mining has been the cornerstone of the South African economy for the last century. Most of the gold mining in South Africa was conducted within the Witwatersrand basin, which contributed to the rapid growth of the city of Johannesburg and capitulated the city to becoming the business and wealth capital of the country. But with gradual depletion of resources, a stoppage in the extraction of underground water from mines and other factors relating to survival of the mining operations over a lengthy period, most of the mines were abandoned and left to pollute the local waterways and groundwater with toxins, heavy metal residue and increased acid mine drainage ensued. The Department of Mineral Resources and Energy commissioned a project whose aim is to monitor, maintain, and mitigate the adverse environmental impacts of polluted water mine water flowing into local streams affecting local ecosystems and livelihoods downstream. As part of mitigation efforts, the diagnosis and monitoring of groundwater or surface water polluted sites has become important. Geophysical surveys, in particular, Resistivity and Magnetics surveys, were selected as some of most suitable techniques for investigation of local ingress points along of one the major streams cutting through the Witwatersrand basin, namely the Blesbokspruit, which is found in the eastern part of the basin. The aim of the surveys was to provide information that could be used to assist in determining possible water loss/ ingress from the Blesbokspriut stream. Modelling of geophysical surveys results offered an in-depth insight into the interaction and pathways of polluted water through mapping of possible ingress channels near the Blesbokspruit. The resistivity - depth profile of the surveyed site exhibit a three(3) layered model with low resistivity values (10 to 200 Ω.m) overburden, which is underlain by a moderate resistivity weathered layer (>300 Ω.m), which sits on a more resistive crystalline bedrock (>500 Ω.m). Two locations of potential ingress channels were mapped across the two traverses at the site. The magnetic survey conducted at the site mapped a major NE-SW trending regional linearment with a strong magnetic signature, which was modeled to depth beyond 100m, with the potential to act as a conduit for dispersion of stream water away from the stream, as it shared a similar orientation with the potential ingress channels as mapped using the resistivity method.

Keywords: eletrictrical resistivity, magnetics survey, blesbokspruit, ingress

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255 Peculiarities of Absorption near the Edge of the Fundamental Band of Irradiated InAs-InP Solid Solutions

Authors: Nodar Kekelidze, David Kekelidze, Elza Khutsishvili, Bela Kvirkvelia

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The semiconductor devices are irreplaceable elements for investigations in Space (artificial Earth satellite, interplanetary space craft, probes, rockets) and for investigation of elementary particles on accelerators, for atomic power stations, nuclear reactors, robots operating on heavily radiation contaminated territories (Chernobyl, Fukushima). Unfortunately, the most important parameters of semiconductors dramatically worsen under irradiation. So creation of radiation-resistant semiconductor materials for opto and microelectronic devices is actual problem, as well as investigation of complicated processes developed in irradiated solid states. Homogeneous single crystals of InP-InAs solid solutions were grown with zone melting method. There has been studied the dependence of the optical absorption coefficient vs photon energy near fundamental absorption edge. This dependence changes dramatically with irradiation. The experiments were performed on InP, InAs and InP-InAs solid solutions before and after irradiation with electrons and fast neutrons. The investigations of optical properties were carried out on infrared spectrophotometer in temperature range of 10K-300K and 1mkm-50mkm spectral area. Radiation fluencies of fast neutrons was equal to 2·1018neutron/cm2 and electrons with 3MeV, 50MeV up to fluxes of 6·1017electron/cm2. Under irradiation, there has been revealed the exponential type of the dependence of the optical absorption coefficient vs photon energy with energy deficiency. The indicated phenomenon takes place at high and low temperatures as well at impurity different concentration and practically in all cases of irradiation by various energy electrons and fast neutrons. We have developed the common mechanism of this phenomenon for unirradiated materials and implemented the quantitative calculations of distinctive parameter; this is in a satisfactory agreement with experimental data. For the irradiated crystals picture get complicated. In the work, the corresponding analysis is carried out. It has been shown, that in the case of InP, irradiated with electrons (Ф=1·1017el/cm2), the curve of optical absorption is shifted to lower energies. This is caused by appearance of the tails of density of states in forbidden band due to local fluctuations of ionized impurity (defect) concentration. Situation is more complicated in the case of InAs and for solid solutions with composition near to InAs when besides noticeable phenomenon there takes place Burstein effect caused by increase of electrons concentration as a result of irradiation. We have shown, that in certain conditions it is possible the prevalence of Burstein effect. This causes the opposite effect: the shift of the optical absorption edge to higher energies. So in given solid solutions there take place two different opposite directed processes. By selection of solid solutions composition and doping impurity we obtained such InP-InAs, solid solution in which under radiation mutual compensation of optical absorption curves displacement occurs. Obtained result let create on the base of InP-InAs, solid solution radiation-resistant optical materials. Conclusion: It was established the nature of optical absorption near fundamental edge in semiconductor materials and it was created radiation-resistant optical material.

Keywords: InAs-InP, electrons concentration, irradiation, solid solutions

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254 Metformin Protects Cardiac Muscle against the Pro-Apoptotic Effects of Hyperglycaemia, Elevated Fatty Acid and Nicotine

Authors: Christopher R. Triggle, Hong Ding, Khaled Machaca, Gnanapragasam Arunachalam

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The antidiabetic drug, metformin, has been in clinical use for over 50 years and remains the first choice drug for the treatment of type two diabetes. In addition to its effectiveness as an oral anti-hyperglycaemic drug metformin also possesses vasculoprotective effects that are assumed to be secondary to its ability to reduce insulin resistance and control glycated hemoglobin levels; however, recent data from our laboratory indicate that metformin also has direct vasoprotective effects that are mediated, at least in part, via the anti-ageing gene, SIRT1. Diabetes is a major risk factor for the development of cardiovascular disease (CVD) and it is also well established that tobacco use further enhances the risk of CVD; however, it is not known whether treatment with metformin can offset the negative effects of diabetes and tobacco use on cardiac function. The current study was therefore designed to investigate 1: the effects of hyperglycaemia (HG) either alone or in the presence of elevated fatty acids (palmitate) and nicotine on the protein expression levels of the deacetylase sirtuin 1 (the protein product of SIRT1), anti-apoptotic Bcl-2, pro-apoptotic BIM and the pro-apoptotic, tumour suppressor protein, acetylated p53 in cardiomyocytes. 2: the ability of metformin to prevent the detrimental effects of HG, palmitate and nicotine on cardiomyocyte survival. Cell culture protocols were designed using a rat cardiomyocyte cell line, H9c2, either under normal glycaemic (NG) conditions of 5.5mM glucose, or hyperglycaemic conditions (HG) of 25mM glucose with, or without, added palmitate (250μM) or nicotine (1.0mM) for 24h. Immuno-blotting was used to detect the expression of sirtuin 1, Bcl-2, BIM, acetylated (Ac)-p53, p53 with β-actin used as the reference protein. Exposure to HG, palmitate, or nicotine alone significantly reduced expression of sirtuin1, Bcl-2 and raised the expression levels of acetylated p53 and BIM; however, the combination of HG, palmitate and nicotine had a synergistic effect to significantly suppress the expression levels of sirtuin 1 and Bcl-2, but further enhanced the expression of Ac-p53, and BIM. The inclusion of 1000μM, but not 50μM, metformin in the H9c2 cell culture protocol prevented the effects of HG, palmitate and nicotine on the pro-apoptotic pathways. Collectively these data indicate that metformin, in addition to its anti-hyperglycaemic and vasculoprotective properties, also has direct cardioprotective actions that offset the negative effects of hyerglycaemia, elevated free fatty acids and nicotine on cardiac cell survival. These data are of particular significance for the treatment of patients with diabetes who are also smokers as the inclusion of metformin in their therapeutic treatment plan should help reduce cardiac-related morbidity and mortality.

Keywords: apoptosis, cardiac muscle, diabetes, metformin, nicotine

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253 Magneto-Luminescent Biocompatible Complexes Based on Alloyed Quantum Dots and Superparamagnetic Iron Oxide Nanoparticles

Authors: A. Matiushkina, A. Bazhenova, I. Litvinov, E. Kornilova, A. Dubavik, A. Orlova

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Magnetic-luminescent complexes based on superparamagnetic iron oxide nanoparticles (SPIONs) and semiconductor quantum dots (QDs) have been recognized as a new class of materials that have high potential in modern medicine. These materials can serve for theranostics of oncological diseases, and also as a target agent for drug delivery. They combine the qualities characteristic of magnetic nanoparticles, that is, magneto-controllability and the ability to local heating under the influence of an external magnetic field, as well as phosphors, due to luminescence of which, for example, early tumor imaging is possible. The complexity of creating complexes is the energy transfer between particles, which quenches the luminescence of QDs in complexes with SPIONs. In this regard, a relatively new type of alloyed (CdₓZn₁₋ₓSeᵧS₁₋ᵧ)-ZnS QDs is used in our work. The presence of a sufficiently thick gradient semiconductor shell in alloyed QDs makes it possible to reduce the probability of energy transfer from QDs to SPIONs in complexes. At the same time, Forster Resonance Energy Transfer (FRET) is a perfect instrument to confirm the formation of complexes based on QDs and different-type energy acceptors. The formation of complexes in the aprotic bipolar solvent dimethyl sulfoxide is ensured by the coordination of the carboxyl group of the stabilizing QD molecule (L-cysteine) on the surface iron atoms of the SPIONs. An analysis of the photoluminescence (PL) spectra has shown that a sequential increase in the SPIONs concentration in the samples is accompanied by effective quenching of the luminescence of QDs. However, it has not confirmed the formation of complexes yet, because of a decrease in the PL intensity of QDs due to reabsorption of light by SPIONs. Therefore, a study of the PL kinetics of QDs at different SPIONs concentrations was made, which demonstrates that an increase in the SPIONs concentration is accompanied by a symbatic reduction in all characteristic PL decay times. It confirms the FRET from QDs to SPIONs, which indicates the QDs/SPIONs complex formation, rather than a spontaneous aggregation of QDs, which is usually accompanied by a sharp increase in the percentage of the QD fraction with the shortest characteristic PL decay time. The complexes have been studied by the magnetic circular dichroism (MCD) spectroscopy that allows one to estimate the response of magnetic material to the applied magnetic field and also can be useful to check SPIONs aggregation. An analysis of the MCD spectra has shown that the complexes have zero residual magnetization, which is an important factor for using in biomedical applications, and don't contain SPIONs aggregates. Cell penetration, biocompatibility, and stability of QDs/SPIONs complexes in cancer cells have been studied using HeLa cell line. We have found that the complexes penetrate in HeLa cell and don't demonstrate cytotoxic effect up to 25 nM concentration. Our results clearly demonstrate that alloyed (CdₓZn₁₋ₓSeᵧS₁₋ᵧ)-ZnS QDs can be successfully used in complexes with SPIONs reached new hybrid nanostructures, which combine bright luminescence for tumor imaging and magnetic properties for targeted drug delivery and magnetic hyperthermia of tumors. Acknowledgements: This work was supported by the Ministry of Science and Higher Education of Russian Federation, goszadanie no. 2019-1080 and was financially supported by Government of Russian Federation, Grant 08-08.

Keywords: alloyed quantum dots, magnetic circular dichroism, magneto-luminescent complexes, superparamagnetic iron oxide nanoparticles

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252 Antiulcer Potential of Heme Oxygenase-1 Inducers

Authors: Gaweł Magdalena, Lipkowska Anna, Olbert Magdalena, Frąckiewicz Ewelina, Librowski Tadeusz, Nowak Gabriel, Pilc Andrzej

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Heme oxygenase-1 (HO-1), also known as heat shock protein 32 (HSP32), has been shown to be implicated in cytoprotection in various organs. Its activation plays a significant role in acute and chronic inflammation, protecting cells from oxidative injury and apoptosis. This inducible isoform of HO catalyzes the first and rate-limiting step in heme degradation to produce equimolar quantities of biologically active products: carbon monoxide (CO), free iron and biliverdin. CO has been reported to possess anti-apoptotic properties. Moreover, it inhibits the production of proinflammatory cytokines and stimulates the synthesis of the anti-inflammatory interleukin-10 (IL-10), as well as promotes vasodilatation at sites of inflammation. The second product of catalytic HO-1 activity, free cytotoxic iron, is promptly sequestered into the iron storage protein ferritin, which lowers the pro-oxidant state of the cell. The third product, biliverdin, is subsequently converted by biliverdin reductase into the bile pigment bilirubin, the most potent endogenous antioxidant among the constituents of human serum, which modulates immune effector functions and suppresses inflammatory response. Furthermore, being one of the so-called stress proteins, HO-1 adaptively responds to different stressors, such as reactive oxygen species (ROS), inflammatory cytokines and heavy metals and thus protects cells against such conditions as ischemia, hemorrhagic shock, heat shock or hypoxia. It is suggested that pharmacologic modulation of HO-1 may represent an effective strategy for prevention of stress and drug-induced gastrointestinal toxicity. HO-1 is constitutively expressed in normal gastric, intestinal and colonic mucosa and up-regulated during inflammation. It has been proven that HO-1 up-regulated by hemin, heme and cobalt-protoporphyrin ameliorates experimental colitis. In addition, the up-regulation of HO-1 partially explains the mechanism of action of 5-aminosalicylic acid (5-ASA), which is used clinically as an anti-colitis agent. In 2009 Ueda et al. has reported for the first time that mucosal protection by Polaprezinc, a chelate compound of zinc and L-carnosine used as an anti-ulcer drug in Japan, is also attributed to induction of HO-1 in the stomach. Since then, inducers of HO-1 are desired subject of research, as they may constitute therapeutically effective anti-ulcer drugs.

Keywords: heme oxygenase-1, gastric lesions, gastroprotection, Polaprezinc

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251 The Influence of the Variety and Harvesting Date on Haskap Composition and Anti-Diabetic Properties

Authors: Aruma Baduge Kithma Hansanee De Silva

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Haskap (Lonicera caerulea L.), also known as blue honeysuckle, is a recently commercialized berry crop in Canada. Haskap berries are rich in polyphenols, including anthocyanins, which are known for potential health-promoting effects. Cyanidin-3-O-glucoside (C3G) is the most prominent anthocyanin of haskap berries. Recent literature reveals the efficacy of C3G in reducing the risk of type 2 diabetes (T2D), which has become an increasingly common health issue around the world. The T2D is characterized as a metabolic disorder of hyperglycemia and insulin resistance. It has been demonstrated that C3G has anti-diabetic effects in various ways, including improvement in insulin sensitivity, and inhibition of activities of carbohydrate-hydrolyzing enzymes, including alpha-amylase and alpha-glucosidase. The goal of this study was to investigate the influence of variety and harvesting date on haskap composition, biological properties, and antidiabetic properties. The polyphenolic compounds present in four commercially grown haskap cultivars, Aurora, Rebecca, Larissa and Evie among five harvesting stages (H1-H5), were extracted separately in 80% ethanol and analyzed to characterize their phenolic profiles. The haskap berries contain different types of polyphenols including flavonoids and phenolic acids. Anthocyanin is the major type of flavonoid. C3G is the most prominent type of anthocyanin, which accounts for 79% of total anthocyanin in all extracts. The variety Larissa at H5 contained the highest average C3G content, and its ethanol extract had the highest (1212.3±63.9 mg/100g FW) while, Evie at H1 contained the lowest C3G content (96.9±40.4 mg/100g FW). The average C3G content of Larissa from H1 – H5 varies from 208 – 1212 mg/100g FW. Quarcetin-3-Rutinoside (Q3Rut) is the major type of flavonol and highest is observed in Rebecca at H4 (47.81 mg/100g FW). The haskap berries also contained phenolic acids, but approximately 95% of the phenolic acids consisted of chlorogenic acid. The cultivar Larissa has a higher level of anthocyanin than the other four cultivars. The highest total phenolic content is observed in Evie at H5 (2.97±1.03 mg/g DW) while the lowest in Rebecca at H1 (1.47±0.96 mg/g DW). The antioxidant capacity of Evie at H5 was higher (14.40±2.21 µmol TE/ g DW) among other cultivars and the lowest observed in Aurora at H3 (5.69±0.34 µmol TE/ g DW). Furthermore, Larissa H5 shows the greatest inhibition of carbohydrate-hydrolyzing enzymes including alpha-glucosidase and alpha-amylase. In conclusion Larissa, at H5 demonstrated highest polyphenol composition and antidiabetic properties.

Keywords: anthocyanin, cyanidin-3-O-glucoside, haskap, type 2 diabetes

Procedia PDF Downloads 438
250 Proximate Composition and Sensory Properties of Complementary Food from Fermented Acha (Digitaria exilis), Soybean and Orange-Flesh Sweet Potato Blends

Authors: N. C. Okoronkwo, I. E. Mbaeyi-Nwaoha, C. P. Agbata

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Childhood malnutrition is one of the most persistent public health problems throughout developing countries, including Nigeria. Demographic and Health survey data from twenty-one developing countries indicated that poor complementary feeding of children aged 6- 23 months contributes to negative growth trends. To reduce malnutrition among children in the society, formulation of complimentary food rich in essential nutrient for optimum growth and development of infants is essential. This study focused on the evaluation of complementary food produced by solid-state fermentation of Acha and Soybean using Rhizopus oligosporus (2710) and Orange-fleshed sweet potatoes (OFSP) using Lactobacillus planterum (B-41621). The raw materials were soaked separately, each in four volumes of 0.9M acetic acid for 16 hours, rinsed with clean water, steam cooked and cooled. Solid-state fermentation (SSF) was carried out by inoculating Acha and Soybean with spore suspension (1x 10⁶spores/ml) of Rhizopus oligosporus (2710) and OFSP with spore suspension (1x 106spores/ml) of Lactobacillus planterum (B-41621). Fermentation which lasted for 72hours was carried out with 24hours sampling. The samples were blended in the following ratios: Acha and soybean 100: 100 (AS), Acha/soybean and OFSP 50: 50(ASO), made into gruel and compared with a commercial infant formula (Cerelac) which served as the control (CTRL). The samples were analyzed for proximate composition using AOAC methods and sensory attributes using a hedonic scale. Results showed that moisture, crude protein, fibre and ash content increased significantly (p<0.05) as fermentation progressed, while carbohydrate and fat content decreased. The protein, moisture, fibre and ash content ranged from 17.10-19.02%, 54.97-56.27%, 7.08-7.60% and2.09-2.38%, respectively, while carbohydrate and fat content ranged from 12.95-10.21% and 5.81-4.52%, respectively. In sensory scores, there were no significant (p>0.05) difference between the average mean scores of colours, texture and consistency of the samples. The sensory score for the overall acceptability ranged from 6.20-7.80. Sample CTRL had the highest score, while sample ASO had the least score. There was no significant (p>0.05) difference between samples CTRL and AS. Solid-state fermentation improved the nutritional content and flavour of the developed complementary food, which is needed for infant growth and development.

Keywords: Complementary food, malnutrition, proximate composition, solid-state fermentation

Procedia PDF Downloads 137
249 Gluten Intolerance, Celiac Disease, and Neuropsychiatric Disorders: A Translational Perspective

Authors: Jessica A. Hellings, Piyushkumar Jani

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Background: Systemic autoimmune disorders are increasingly implicated in neuropsychiatric illness, especially in the setting of treatment resistance in individuals of all ages. Gluten allergy in fullest extent results in celiac disease, affecting multiple organs including central nervous system (CNS). Clinicians often lack awareness of the association between neuropsychiatric illness and gluten allergy, partly since many such research studies are published in immunology and gastroenterology journals. Methods: Following a Pubmed literature search and online searches on celiac disease websites, 40 articles are critically reviewed in detail. This work reviews celiac disease, gluten intolerance and current evidence of their relationship to neuropsychiatric and systemic illnesses. The review also covers current work-up and diagnosis, as well as dietary interventions, gluten restriction outcomes, and future research directions. Results: Gluten allergy in susceptible individuals damages the small intestine, producing a leaky gut and malabsorption state, as well as allowing antibodies into the bloodstream, which attack major organs. Lack of amino acid precursors for neurotransmitter synthesis together with antibody-associated brain changes and hypoperfusion may result in neuropsychiatric illness. This is well documented; however, studies in neuropsychiatry are often small. In the large CATIE trial, subjects with schizophrenia had significantly increased antibodies to tissue transglutaminase (TTG), and antigliadin antibodies, both significantly greater gluten antibodies than in control subjects. On later follow up, TTG-6 antibodies were identified in these subjects’ brains but not in their intestines. Significant evidence mostly from small studies also exists for gluten allergy and celiac-related depression, anxiety disorders, attention-deficit/hyperactivity disorder, autism spectrum disorders, ataxia, and epilepsy. Dietary restriction of gluten resulted in remission in several published cases, including for treatment-resistant schizophrenia. Conclusions: Ongoing and larger studies are needed of the diagnosis and treatment efficacy of the gluten-free diet in neuropsychiatric illness. Clinicians should ask about the patient history of anemia, hypothyroidism, irritable bowel syndrome and family history of benefit from the gluten-free diet, not limited to but especially in cases of treatment resistance. Obtaining gluten antibodies by a simple blood test, and referral for gastrointestinal work-up in positive cases should be considered.

Keywords: celiac, gluten, neuropsychiatric, translational

Procedia PDF Downloads 144
248 Sweet to Bitter Perception Parageusia: Case of Posterior Inferior Cerebellar Artery Territory Diaschisis

Authors: I. S. Gandhi, D. N. Patel, M. Johnson, A. R. Hirsch

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Although distortion of taste perception following a cerebrovascular event may seem to be a frivolous consequence of a classic stroke presentation, altered taste perception places patients at an increased risk for malnutrition, weight loss, and depression, all of which negatively impact the quality of life. Impaired taste perception can result from a wide variety of cerebrovascular lesions to various locations, including pons, insular cortices, and ventral posteromedial nucleus of the thalamus. Wallenberg syndrome, also known as a lateral medullary syndrome, has been described to impact taste; however, specific sweet to bitter taste dysgeusia from a territory infarction is an infrequent event; as such, a case is presented. One year prior to presentation, this 64-year-old right-handed woman, suffered a right posterior inferior cerebellar artery aneurysm rupture with resultant infarction, culminating in a ventriculoperitoneal shunt placement. One and half months after this event, she noticed the gradual onset of lack of ability to taste sweet, to eventually all sweet food tasting bitter. Since the onset of her chemosensory problems, the patient has lost 60-pounds. Upon gustatory testing, the patient's taste threshold showed ageusia to sucrose and hydrochloric acid, while normogeusia to sodium chloride, urea, and phenylthiocarbamide. The gustatory cortex is made in part by the right insular cortex as well as the right anterior operculum, which are primarily involved in the sensory taste modalities. In this model, sweet is localized in the posterior-most along with the rostral aspect of the right insular cortex, notably adjacent to the region responsible for bitter taste. The sweet to bitter dysgeusia in our patient suggests the presence of a lesion in this localization. Although the primary lesion in this patient was located in the right medulla of the brainstem, neurodegeneration in the rostal and posterior-most aspect, of the right insular cortex may have occurred due to diaschisis. Diaschisis has been described as neurophysiological changes that occur in remote regions to a focal brain lesion. Although hydrocephalus and vasospasm due to aneurysmal rupture may explain the distal foci of impairment, the gradual onset of dysgeusia is more indicative of diaschisis. The perception of sweet, now tasting bitter, suggests that in the absence of sweet taste reception, the intrinsic bitter taste of food is now being stimulated rather than sweet. In the evaluation and treatment of taste parageusia secondary to cerebrovascular injury, prophylactic neuroprotective measures may be worthwhile. Further investigation is warranted.

Keywords: diaschisis, dysgeusia, stroke, taste

Procedia PDF Downloads 158
247 Prevalence of Nutrient Deficiencies in Older Adults: Results from the Japan National Health and Nutrition Survey 2014

Authors: Ye Sun, Han-Youl Lee, Kathy Musa-Veloso, Nabil Bosco

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Japan has been experiencing global ageing of population with the World’s leading life expectancy (80.8 y for men and 86.9 y for women) and among the lowest birth rate. Preventive nutrition-based approaches have been identified by the health authorities as one of the strategies to increase the healthy life expectancy and reduce the healthcare costs. However, the nutritional needs and status of the senior population have not been well characterized to provide targeted solutions. This study aims to describe the age- and gender-specific prevalence of inadequacy of macro- and micronutrients intake based on the latest Japan National Health and Nutrition Survey (JNHNS) 2014. JNHNS collected data on the consumption of foods and beverages using 1-day semi-weight household dietary record. Nutrient intake levels were then calculated using the Japanese standard tables of food composition. Where applicable, Japanese population-specific estimated average requirements (EAR) were used as a benchmark to determine the prevalence of potential nutrient intake inadequacy, and adequate intake (AI) were used for nutrients with no available EARs. In all, 3403 senior adults aged 60 y and above and 3324 young adults aged 19 to 59 y were included in the 2014 JNHNS. Age- and gender-specific differences were observed in the mean nutrient intakes as well as the prevalence of inadequacy. Among the 22 nutrients examined, the prevalence of inadequacy for iron, vitamin C, magnesium, potassium, and folic acid in the senior adults was significantly lower than young adults, suggesting potentially healthier dietary choices by the seniors. However, there was still a considerable proportion of seniors who did not meet the requirement for key nutrients like vitamin B1 (67%), calcium (57%), vitamin A (48%), magnesium (47%), vitamin E (44%), and vitamin B6 (41%). Inadequate nutrient intake is generally more prevalent among elderly males than females for many nutrients, with the exception of iron (prevalence of inadequacy: 21% versus 42%) which could partly be explained by the higher intake recommendations for the females. In conclusion, high prevalence of nutrient inadequacy exists in older adults, with a potentially worsened picture for men. Such inadequacies could have multiple health implications including physical frailty and mental health. Further study is warranted to investigate the food consumption patterns that could explain the observed nutrient inadequacies, and to eventually develop nutrition-based solutions tailored to the needs of specific subgroups of the population.

Keywords: ageing, national health and nutrition survey, nutrients, nutrition

Procedia PDF Downloads 128
246 Immuno-Protective Role of Mucosal Delivery of Lactococcus lactis Expressing Functionally Active JlpA Protein on Campylobacter jejuni Colonization in Chickens

Authors: Ankita Singh, Chandan Gorain, Amirul I. Mallick

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Successful adherence of the mucosal epithelial cells is the key early step for Campylobacter jejuni pathogenesis (C. jejuni). A set of Surface Exposed Colonization Proteins (SECPs) are among the major factors involved in host cell adherence and invasion of C. jejuni. Among them, constitutively expressed surface-exposed lipoprotein adhesin of C. jejuni, JlpA, interacts with intestinal heat shock protein 90 (hsp90α) and contributes in disease progression by triggering pro-inflammatory response via activation of NF-κB and p38 MAP kinase pathway. Together with its ability to express in the bacterial surface, higher sequence conservation and predicted predominance of several B cells epitopes, JlpA protein reserves its potential to become an effective vaccine candidate against wide range of Campylobacter sps including C. jejuni. Given that chickens are the primary sources for C. jejuni and persistent gut colonization remain as major cause for foodborne pathogenesis to humans, present study explicitly used chickens as model to test the immune-protective efficacy of JlpA protein. Taking into account that gastrointestinal tract is the focal site for C. jejuni colonization, to extrapolate the benefit of mucosal (intragastric) delivery of JlpA protein, a food grade Nisin inducible Lactic acid producing bacteria, Lactococcus lactis (L. lactis) was engineered to express recombinant JlpA protein (rJlpA) in the surface of the bacteria. Following evaluation of optimal surface expression and functionality of recombinant JlpA protein expressed by recombinant L. lactis (rL. lactis), the immune-protective role of intragastric administration of live rL. lactis was assessed in commercial broiler chickens. In addition to the significant elevation of antigen specific mucosal immune responses in the intestine of chickens that received three doses of rL. lactis, marked upregulation of Toll-like receptor 2 (TLR2) gene expression in association with mixed pro-inflammatory responses (both Th1 and Th17 type) was observed. Furthermore, intragastric delivery of rJlpA expressed by rL. lactis, but not the injectable form, resulted in a significant reduction in C. jejuni colonization in chickens suggesting that mucosal delivery of live rL. lactis expressing JlpA serves as a promising vaccine platform to induce strong immune-protective responses against C. jejuni in chickens.

Keywords: chickens, lipoprotein adhesion of Campylobacter jejuni, immuno-protection, Lactococcus lactis, mucosal delivery

Procedia PDF Downloads 121
245 Prenatal Paraben Exposure Impacts Infant Overweight Development and in vitro Adipogenesis

Authors: Beate Englich, Linda Schlittenbauer, Christiane Pfeifer, Isabel Kratochvil, Michael Borte, Gabriele I. Stangl, Martin von Bergen, Thorsten Reemtsma, Irina Lehmann, Kristin M. Junge

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The worldwide production of endocrine disrupting compounds (EDC) has risen dramatically over the last decades, as so has the prevalence for obesity. Many EDCs are believed to contribute to this obesity epidemic, by enhancing adipogenesis or disrupting relevant metabolism. This effect is most tremendous in the early prenatal period when priming effects find a highly vulnerable time window. Therefore, we investigate the impact of parabens on childhood overweight development and adipogenesis in general. Parabens are ester of 4-hydroxy-benzoic acid and part of many cosmetic products or food packing. Therefore, ubiquitous exposure can be found in the westernized world, with exposure already starting during the sensitive prenatal period. We assessed maternal cosmetic product consumption, prenatal paraben exposure and infant BMI z-scores in the prospective German LINA cohort. In detail, maternal urinary concentrations (34 weeks of gestation) of methyl paraben (MeP), ethyl paraben (EtP), n-propyl paraben (PrP) and n-butyl paraben (BuP) were quantified using UPLC-MS/MS. Body weight and height of their children was assessed during annual clinical visits. Further, we investigated the direct influence of those parabens on adipogenesis in-vitro using a human mesenchymal stem cell (MSC) differentiation assay to mimic a prenatal exposure scenario. MSC were exposed to 0.1 – 50 µM paraben during the entire differentiation period. Differentiation outcome was monitored by impedance spectrometry, real-time PCR and triglyceride staining. We found that maternal cosmetic product consumption was highly correlated with urinary paraben concentrations at pregnancy. Further, prenatal paraben exposure was linked to higher BMI Z-scores in children. Our in-vitro analysis revealed that especially the long chained paraben BuP stimulates adipogenesis by increasing the expression of adipocyte specific genes (PPARγ, ADIPOQ, LPL, etc.) and triglyceride storage. Moreover, we found that adiponectin secretion is increased whereas leptin secretion is reduced under BuP exposure in-vitro. Further mechanistic analysis for receptor binding and activation of PPARγ and other key players in adipogenesis are currently in process. We conclude that maternal cosmetic product consumption is linked to prenatal paraben exposure of children and contributes to the development of infant overweight development by triggering key pathways of adipogenesis.

Keywords: adipogenesis, endocrine disruptors, paraben, prenatal exposure

Procedia PDF Downloads 251
244 The Efficacy of Thymbra spicata Ethanolic Extract and its Main Component Carvacrol on In vitro Model of Metabolically-Associated Dysfunctions

Authors: Farah Diab, Mohamad Khalil, Francesca Storace, Francesca Baldini, Piero Portincasaa, Giulio Lupidi, Laura Vergani

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Thymbra spicata is a thyme-like plant belonging to the Lamiaceae family that shows a global distribution, especially in the eastern Mediterranean region. Leaves of T. spicata contain large amounts of phenols such as phenolic acids (rosmarinic acid), phenolic monoterpenes (carvacrol), and flavonoids. In Lebanon, T. spicata is currently used as a culinary herb in salad and infusion, as well as for traditional medicinal purposes. Carvacrol (5-isopropyl-2-methyl phenol), the most abundant polyphenol in the organic extract and essential oils, has a great array of pharmacological properties. In fact, carvacrol is largely employed as a food additive and neutraceutical agent. Our aim is to investigate the beneficial effects of T. spicata ethanolic extract (TE) and its main component, carvacrol, using in vitro models of hepatic steatosis and endothelial dysfunction. As a further point, we focused on investigating if and how the binding of carvacrol to albumin, the physiological transporter for drugs in the blood, might be altered by the presence of high levels of fatty acids (FAs), thus impairing the carvacrol bio-distribution in vivo. For that reason, hepatic FaO cells treated with exogenous FAs such as oleate and palmitate mimic hepatosteatosis; endothelial HECV cells exposed to hydrogen peroxide are a model of endothelial dysfunction. In these models, we measured lipid accumulation, free radical production, lipoperoxidation, and nitric oxide release before and after treatment with carvacrol. The carvacrol binding to albumin with/without high levels of long-chain FAs was assessed by absorption and emission spectroscopies. Our findings show that both TE and carvacrol (i) counteracted lipid accumulation in hepatocytes by decreasing the intracellular and extracellular lipid contents in steatotic FaO cells; (ii) decreased oxidative stress in endothelial cells by significantly reducing lipoperoxidation and free radical production, as well as, attenuating the nitric oxide release; (ii) high levels of circulating FAs reduced the binding of carvacrol to albumin. The beneficial effects of TE and carvacrol on both hepatic and endothelial cells point to a nutraceutical potential. However, high levels of circulating FAs, such as those occurring in metabolic disorders, might hinder the carvacrol transport, bio-distribution, and pharmacodynamics.

Keywords: carvacrol, endothelial dysfunction, fatty acids, non-alcoholic fatty liver diseases, serum albumin

Procedia PDF Downloads 161
243 Identification of Failures Occurring on a System on Chip Exposed to a Neutron Beam for Safety Applications

Authors: S. Thomet, S. De-Paoli, F. Ghaffari, J. M. Daveau, P. Roche, O. Romain

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In this paper, we present a hardware module dedicated to understanding the fail reason of a System on Chip (SoC) exposed to a particle beam. Impact of Single-Event Effects (SEE) on processor-based SoCs is a concern that has increased in the past decade, particularly for terrestrial applications with automotive safety increasing requirements, as well as consumer and industrial domains. The SEE created by the impact of a particle on an SoC may have consequences that can end to instability or crashes. Specific hardening techniques for hardware and software have been developed to make such systems more reliable. SoC is then qualified using cosmic ray Accelerated Soft-Error Rate (ASER) to ensure the Soft-Error Rate (SER) remains in mission profiles. Understanding where errors are occurring is another challenge because of the complexity of operations performed in an SoC. Common techniques to monitor an SoC running under a beam are based on non-intrusive debug, consisting of recording the program counter and doing some consistency checking on the fly. To detect and understand SEE, we have developed a module embedded within the SoC that provide support for recording probes, hardware watchpoints, and a memory mapped register bank dedicated to software usage. To identify CPU failure modes and the most important resources to probe, we have carried out a fault injection campaign on the RTL model of the SoC. Probes are placed on generic CPU registers and bus accesses. They highlight the propagation of errors and allow identifying the failure modes. Typical resulting errors are bit-flips in resources creating bad addresses, illegal instructions, longer than expected loops, or incorrect bus accesses. Although our module is processor agnostic, it has been interfaced to a RISC-V by probing some of the processor registers. Probes are then recorded in a ring buffer. Associated hardware watchpoints are allowing to do some control, such as start or stop event recording or halt the processor. Finally, the module is also providing a bank of registers where the firmware running on the SoC can log information. Typical usage is for operating system context switch recording. The module is connected to a dedicated debug bus and is interfaced to a remote controller via a debugger link. Thus, a remote controller can interact with the monitoring module without any intrusiveness on the SoC. Moreover, in case of CPU unresponsiveness, or system-bus stall, the recorded information can still be recovered, providing the fail reason. A preliminary version of the module has been integrated into a test chip currently being manufactured at ST in 28-nm FDSOI technology. The module has been triplicated to provide reliable information on the SoC behavior. As the primary application domain is automotive and safety, the efficiency of the module will be evaluated by exposing the test chip under a fast-neutron beam by the end of the year. In the meantime, it will be tested with alpha particles and electromagnetic fault injection (EMFI). We will report in the paper on fault-injection results as well as irradiation results.

Keywords: fault injection, SoC fail reason, SoC soft error rate, terrestrial application

Procedia PDF Downloads 213
242 Active Filtration of Phosphorus in Ca-Rich Hydrated Oil Shale Ash Filters: The Effect of Organic Loading and Form of Precipitated Phosphatic Material

Authors: Päärn Paiste, Margit Kõiv, Riho Mõtlep, Kalle Kirsimäe

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For small-scale wastewater management, the treatment wetlands (TWs) as a low cost alternative to conventional treatment facilities, can be used. However, P removal capacity of TW systems is usually problematic. P removal in TWs is mainly dependent on the physico–chemical and hydrological properties of the filter material. Highest P removal efficiency has been shown trough Ca-phosphate precipitation (i.e. active filtration) in Ca-rich alkaline filter materials, e.g. industrial by-products like hydrated oil shale ash (HOSA), metallurgical slags. In this contribution we report preliminary results of a full-scale TW system using HOSA material for P removal for a municipal wastewater at Nõo site, Estonia. The main goals of this ongoing project are to evaluate: a) the long-term P removal efficiency of HOSA using real waste water; b) the effect of high organic loading rate; c) variable P-loading effects on the P removal mechanism (adsorption/direct precipitation); and d) the form and composition of phosphate precipitates. Onsite full-scale experiment with two concurrent filter systems for treatment of municipal wastewater was established in September 2013. System’s pretreatment steps include septic tank (2 m2) and vertical down-flow LECA filters (3 m2 each), followed by horizontal subsurface HOSA filters (effective volume 8 m3 each). Overall organic and hydraulic loading rates of both systems are the same. However, the first system is operated in a stable hydraulic loading regime and the second in variable loading regime that imitates the wastewater production in an average household. Piezometers for water and perforated sample containers for filter material sampling were incorporated inside the filter beds to allow for continuous in-situ monitoring. During the 18 months of operation the median removal efficiency (inflow to outflow) of both systems were over 99% for TP, 93% for COD and 57% for TN. However, we observed significant differences in the samples collected in different points inside the filter systems. In both systems, we observed development of preferred flow paths and zones with high and low loadings. The filters show formation and a gradual advance of a “dead” zone along the flow path (zone with saturated filter material characterized by ineffective removal rates), which develops more rapidly in the system working under variable loading regime. The formation of the “dead” zone is accompanied by the growth of organic substances on the filter material particles that evidently inhibit the P removal. Phase analysis of used filter materials using X-ray diffraction method reveals formation of minor amounts of amorphous Ca-phosphate precipitates. This finding is supported by ATR-FTIR and SEM-EDS measurements, which also reveal Ca-phosphate and authigenic carbonate precipitation. Our first experimental results demonstrate that organic pollution and loading regime significantly affect the performance of hydrated ash filters. The material analyses also show that P is incorporated into a carbonate substituted hydroxyapatite phase.

Keywords: active filtration, apatite, hydrated oil shale ash, organic pollution, phosphorus

Procedia PDF Downloads 258
241 Analysis of Reduced Mechanisms for Premixed Combustion of Methane/Hydrogen/Propane/Air Flames in Geometrically Modified Combustor and Its Effects on Flame Properties

Authors: E. Salem

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Combustion has been used for a long time as a means of energy extraction. However, in recent years, there has been a further increase in air pollution, through pollutants such as nitrogen oxides, acid etc. In order to solve this problem, there is a need to reduce carbon and nitrogen oxides through learn burning modifying combustors and fuel dilution. A numerical investigation has been done to investigate the effectiveness of several reduced mechanisms in terms of computational time and accuracy, for the combustion of the hydrocarbons/air or diluted with hydrogen in a micro combustor. The simulations were carried out using the ANSYS Fluent 19.1. To validate the results “PREMIX and CHEMKIN” codes were used to calculate 1D premixed flame based on the temperature, composition of burned and unburned gas mixtures. Numerical calculations were carried for several hydrocarbons by changing the equivalence ratios and adding small amounts of hydrogen into the fuel blends then analyzing the flammable limit, the reduction in NOx and CO emissions, then comparing it to experimental data. By solving the conservations equations, several global reduced mechanisms (2-9-12) were obtained. These reduced mechanisms were simulated on a 2D cylindrical tube with dimensions of 40 cm in length and 2.5 cm diameter. The mesh of the model included a proper fine quad mesh, within the first 7 cm of the tube and around the walls. By developing a proper boundary layer, several simulations were performed on hydrocarbon/air blends to visualize the flame characteristics than were compared with experimental data. Once the results were within acceptable range, the geometry of the combustor was modified through changing the length, diameter, adding hydrogen by volume, and changing the equivalence ratios from lean to rich in the fuel blends, the results on flame temperature, shape, velocity and concentrations of radicals and emissions were observed. It was determined that the reduced mechanisms provided results within an acceptable range. The variation of the inlet velocity and geometry of the tube lead to an increase of the temperature and CO2 emissions, highest temperatures were obtained in lean conditions (0.5-0.9) equivalence ratio. Addition of hydrogen blends into combustor fuel blends resulted in; reduction in CO and NOx emissions, expansion of the flammable limit, under the condition of having same laminar flow, and varying equivalence ratio with hydrogen additions. The production of NO is reduced because the combustion happens in a leaner state and helps in solving environmental problems.

Keywords: combustor, equivalence-ratio, hydrogenation, premixed flames

Procedia PDF Downloads 99
240 Phytoremediation; Pb, Cr and Cd Accumulation in Fruits and Leaves of Vitis Vinifera L. From Air Pollutions and Intraction between Their Uptake Based on the Distance from the Main Road

Authors: Fatemeh Mohsennezhad

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Air pollution is one of major problems for environment. Providing healthy food and protecting water sources from pollution has been one of the concerns of human societies and decision-making centers so that protecting food from pollution, detecting sources of pollution and measuring them become important. Nutritive and political significance of grape in this area, extensive use of leaf and fruit of this plant and development of urban areas around grape gardens and construction of Tabriz – Miandoab road, which is the most important link between East and West Azarbaijan, led us to examine the impact of this road construction and urban environment pollutants such as lead chromium and cadmium on the quality of this valuable crop. First, the samples were taken from different adjacent places and medium distances from the road, each place being located exactly by Google earth and GPS. Digestion was done through burning dry material and hydrochloric acid and their ashes were analyzed by atomic absorption to determine (Pb, Cr, Cd) accumulations. In this experiments effects of 2 following factors were examined as a variable: Garden distance from the main road with levels 1: For 50 meters, 2: For 120-200 meters, 3: For above 800 meters, and plant organ with levels 1: For fruit, 2: For leaves. At the end, the results were processed by SPSS software. 3.54 ppm, the most lead quantity, was at sample No. 54 in fruits with 800 meters distance from the road and 1.00 ppm was the least lead quantity at sample No. 50 in fruits with 1000 meters from the road. In leaves, the most lead quantity was 19.16 ppm at sample No. 15 with 50 meters distance from the road and the least quantity was 1.41 ppm at sample No. 31 with 50 meters from the road. Pb uptake is significantly different at 50 meters and 200 meters distance. It means that Pb uptake near the main road is the highest. But this result is not true for others elements. Distance has not a meaningful effect on Cr uptake. The result of analysis of variation in distance and plant organ for Cd showed that between fruit and leaf, Cd uptake is significantly different. But distance and interaction between distance and plant organ is not meaningful. There is neither meaningful interaction between these elements uptakes in fruits nor in leaves. If leaves and fruits, assumed all together, showed a very meaningful integration between heavy metal accumulations. It means that each of these elements causes uptake others without considering special organs. In the tested area, it became clear that, from the accumulation of heavy metals perspective, there is no meaningful difference in existing distance between road and garden. There is a meaningful difference among heavy metals accumulation. In other words, increase ratio of one metal to another was different from the resulted differences shown in corresponding graphs. Interaction among elements and distance between garden and road was not meaningful.

Keywords: Vitis vinifera L., phytoremediation, heavy metals accumulation, lead, chromium, cadmium

Procedia PDF Downloads 331
239 Non-Melanoma Skin Cancer of Cephalic Extremity – Clinical and Histological Aspects

Authors: Razvan Mercut, Mihaela Ionescu, Vlad Parvanescu, Razvan Ghita, Tudor-Gabriel Caragea, Cristina Simionescu, Marius-Eugen Ciurea

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Introduction: Over the past years, the incidence of non-melanoma skin cancer (NMSC) has continuously increased, being one of the most commonly diagnosed carcinomasofthe cephalic extremity. NMSC regroups basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Merkel cell carcinoma, cutaneous lymphoma, and sarcoma. The most common forms are BCC and SCC, both still implying a significant level of morbidity due to local invasion (especially BCC), even if the overall death rates are declining. The objective of our study was the evaluation of clinical and histological aspects of NMSC for a group of patients with BCC and SCC, from Craiova, a south-western major city in Romania. Materialand method: Our study lot comprised 65 patients, with an almost equal distribution of sexes, and ages between 23-91 years old (mean value±standard deviation62.61±16.67), all treated within the Clinic of Plastic Surgery and Reconstructive Microsurgery, Clinical Emergency County Hospital Craiova, Romania, between 2019-2020. In order to determine the main morphological characteristics of both studied cancers, we used paraffin embedding techniques, with various staining methods:hematoxylin-eosin, Masson's trichrome stain with aniline blue, and Periodic acid-schiffAlcian Blue. The statistical study was completed using Microsoft Excel (Microsoft Corp., Redmond, WA, USA), with XLSTAT (Addinsoft SARL, Paris, France). Results: The overall results of our study indicate that BCC accounts for 67.69% of all NMSC forms; SCC covers 27.69%, while 4.62% are representedby other forms. The most frequent site is the nose for BCC (27.69%, 18 patients), being followed by preauricular regions, forehead, and periorbital areas. For patients with SCC, tumors were mainly located at lips level (66.67%, 12 patients). The analysis of NMSC histological forms indicated that nodular BCC is predominant (45.45%, 20 patients), as well as ulcero-vegetant SCC (38.89%, 7 patients). We have not identified any topographic characteristics or NMSC forms significantly related to age or sex. Conclusions: The most frequent NMSC form identified for our study lot was BCC. The preferred location was the nose for BCC. For SCC, the oral cavity is the most frequent anatomical site, especially the lips level. Nodular BCC and ulcero-vegetant SCC were the most commonly identified histological types. Our findings emphasize the need for periodic screening, in order to improve prevention and early treatment for these malignancies.

Keywords: non-melanoma skin cancer, basal cell carcinoma, squamous cell carcinoma, histological

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238 The Diagnostic Utility and Sensitivity of the Xpert® MTB/RIF Assay in Diagnosing Mycobacterium tuberculosis in Bone Marrow Aspirate Specimens

Authors: Nadhiya N. Subramony, Jenifer Vaughan, Lesley E. Scott

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In South Africa, the World Health Organisation estimated 454000 new cases of Mycobacterium tuberculosis (M.tb) infection (MTB) in 2015. Disseminated tuberculosis arises from the haematogenous spread and seeding of the bacilli in extrapulmonary sites. The gold standard for the detection of MTB in bone marrow is TB culture which has an average turnaround time of 6 weeks. Histological examinations of trephine biopsies to diagnose MTB also have a time delay owing mainly to the 5-7 day processing period prior to microscopic examination. Adding to the diagnostic delay is the non-specific nature of granulomatous inflammation which is the hallmark of MTB involvement of the bone marrow. A Ziehl-Neelson stain (which highlights acid-fast bacilli) is therefore mandatory to confirm the diagnosis but can take up to 3 days for processing and evaluation. Owing to this delay in diagnosis, many patients are lost to follow up or remain untreated whilst results are awaited, thus encouraging the spread of undiagnosed TB. The Xpert® MTB/RIF (Cepheid, Sunnyvale, CA) is the molecular test used in the South African national TB program as the initial diagnostic test for pulmonary TB. This study investigates the optimisation and performance of the Xpert® MTB/RIF on bone marrow aspirate specimens (BMA), a first since the introduction of the assay in the diagnosis of extrapulmonary TB. BMA received for immunophenotypic analysis as part of the investigation into disseminated MTB or in the evaluation of cytopenias in immunocompromised patients were used. Processing BMA on the Xpert® MTB/RIF was optimised to ensure bone marrow in EDTA and heparin did not inhibit the PCR reaction. Inactivated M.tb was spiked into the clinical bone marrow specimen and distilled water (as a control). A volume of 500mcl and an incubation time of 15 minutes with sample reagent were investigated as the processing protocol. A total of 135 BMA specimens had sufficient residual volume for Xpert® MTB/RIF testing however 22 specimens (16.3%) were not included in the final statistical analysis as an adequate trephine biopsy and/or TB culture was not available. Xpert® MTB/RIF testing was not affected by BMA material in the presence of heparin or EDTA, but the overall detection of MTB in BMA was low compared to histology and culture. Sensitivity of the Xpert® MTB/RIF compared to both histology and culture was 8.7% (95% confidence interval (CI): 1.07-28.04%) and sensitivity compared to histology only was 11.1% (95% CI: 1.38-34.7%). Specificity of the Xpert® MTB/RIF was 98.9% (95% CI: 93.9-99.7%). Although the Xpert® MTB/RIF generates a faster result than histology and TB culture and is less expensive than culture and drug susceptibility testing, the low sensitivity of the Xpert® MTB/RIF precludes its use for the diagnosis of MTB in bone marrow aspirate specimens and warrants alternative/additional testing to optimise the assay.

Keywords: bone marrow aspirate , extrapulmonary TB, low sensitivity, Xpert® MTB/RIF

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237 Foregrounding Events in Modern Sundanese: The Pragmatics of Particle-to-Active Voice Marking Shift

Authors: Rama Munajat

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Discourse information levels may be viewed from either a background-foreground distinction or a multi-level perspective, and cross-linguistic studies on this area suggest that each information level is marked by a specific linguistic device. In this sense, Sundanese, spoken in Indonesia’s West Javanese Province, further differentiates the background and foreground information into ordinary and significant types. This paper will report an ongoing shift from particle-to-active voice marking in the way Sundanese signals foregrounding events. The shift relates to decades of contact with Bahasa Indonesia (Indonesia’s official language) and linguistic compatibility between the two surface marking strategies. Representative data analyzed include three groups of short stories in both Sundanese and Bahasa Indonesia (Indonesian) published in three periods: before 1945, 1965-2006, and 2016-2019. In the first group of Sundanese data, forward-moving events dominantly appear in particle KA (Kecap Anteuran, word-accompanying) constructions, where the KA represents different particles that co-occur with a special group of verbs. The second group, however, shows that the foregrounded events are more frequently described in active-voice forms with a subject-predicate (SP) order. Subsequently, the third offers stronger evidence for the use of the SP structure. As for the Indonesian data, the foregrounding events in the first group occur in verb-initial and passive-voice constructions, while in the second and third, the events more frequently appear in active-voice structures (subject-predicate sequence). The marking shift above suggests a structural influence from Indonesian, stemmed from generational differences among authors of the Sundanese short stories, particularly related to their education and language backgrounds. The first group of short stories – published before 1945 or before Indonesia's independence from Dutch – were written by native speakers of Sundanese who spoke Indonesian as a foreign language and went through the Dutch education system. The second group of authors, on the other hand, represents a generation of Sundanese native speakers who spoke Indonesian as a second language. Finally, the third group consists of authors who are bilingual speakers of both Sundanese and Indonesian. The data suggest that the last two groups of authors completed the Indonesian education system. With these, the use of subject-predicate sequences to denote foregrounding events began to appear more frequently in the second group and then became more dominant in those of the third. The coded data also signify that cohesion, coherence, and pragmatic purposes in Particle KA constructions are intact in their respective active-voice structure counterparts. For instance, the foregrounding events in Particle KA constructions occur in Sentence-initial KA and Pre-verbal KA forms, whereas those in the active-voice are described in Subject-Predicate (SP) and Zero-Subject active-voice patterns. Cross-language data further demonstrate that the Sentence-initial KA and the SP active-voice structures each contain an overt noun phrase (NP) co-referential with one of the entities introduced in a preceding context. Similarly, the pre-verbal KA and Zero-Subject active-voice patterns have a deleted noun phrase unambiguously referable to the only one entity previously mentioned. The presence and absence of an NP inform a pragmatic strategy to place prominence on topic/given and comment/new information, respectively.

Keywords: discourse analysis, foregrounding marking, pragmatics, language contact

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236 Biofiltration Odour Removal at Wastewater Treatment Plant Using Natural Materials: Pilot Scale Studies

Authors: D. Lopes, I. I. R. Baptista, R. F. Vieira, J. Vaz, H. Varela, O. M. Freitas, V. F. Domingues, R. Jorge, C. Delerue-Matos, S. A. Figueiredo

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Deodorization is nowadays a need in wastewater treatment plants. Nitrogen and sulphur compounds, volatile fatty acids, aldehydes and ketones are responsible for the unpleasant odours, being ammonia, hydrogen sulphide and mercaptans the most common pollutants. Although chemical treatments of the air extracted are efficient, these are more expensive than biological treatments, namely due the use of chemical reagents (commonly sulphuric acid, sodium hypochlorite and sodium hydroxide). Biofiltration offers the advantage of avoiding the use of reagents (only in some cases, nutrients are added in order to increase the treatment efficiency) and can be considered a sustainable process when the packing medium used is of natural origin. In this work the application of some natural materials locally available was studied both at laboratory and pilot scale, in a real wastewater treatment plant. The materials selected for this study were indigenous Portuguese forest materials derived from eucalyptus and pinewood, such as woodchips and bark, and coconut fiber was also used for comparison purposes. Their physico-chemical characterization was performed: density, moisture, pH, buffer and water retention capacity. Laboratory studies involved batch adsorption studies for ammonia and hydrogen sulphide removal and evaluation of microbiological activity. Four pilot-scale biofilters (1 cubic meter volume) were installed at a local wastewater treatment plant treating odours from the effluent receiving chamber. Each biofilter contained a different packing material consisting of mixtures of eucalyptus bark, pine woodchips and coconut fiber, with added buffering agents and nutrients. The odour treatment efficiency was monitored over time, as well as other operating parameters. The operation at pilot scale suggested that between the processes involved in biofiltration - adsorption, absorption and biodegradation - the first dominates at the beginning, while the biofilm is developing. When the biofilm is completely established, and the adsorption capacity of the material is reached, biodegradation becomes the most relevant odour removal mechanism. High odour and hydrogen sulphide removal efficiencies were achieved throughout the testing period (over 6 months), confirming the suitability of the materials selected, and mixtures thereof prepared, for biofiltration applications.

Keywords: ammonia hydrogen sulphide and removal, biofiltration, natural materials, odour control in wastewater treatment plants

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235 Ragging and Sludging Measurement in Membrane Bioreactors

Authors: Pompilia Buzatu, Hazim Qiblawey, Albert Odai, Jana Jamaleddin, Mustafa Nasser, Simon J. Judd

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Membrane bioreactor (MBR) technology is challenged by the tendency for the membrane permeability to decrease due to ‘clogging’. Clogging includes ‘sludging’, the filling of the membrane channels with sludge solids, and ‘ragging’, the aggregation of short filaments to form long rag-like particles. Both sludging and ragging demand manual intervention to clear out the solids, which is time-consuming, labour-intensive and potentially damaging to the membranes. These factors impact on costs more significantly than membrane surface fouling which, unlike clogging, is largely mitigated by the chemical clean. However, practical evaluation of MBR clogging has thus far been limited. This paper presents the results of recent work attempting to quantify sludging and clogging based on simple bench-scale tests. Results from a novel ragging simulation trial indicated that rags can be formed within 24-36 hours from dispersed < 5 mm-long filaments at concentrations of 5-10 mg/L under gently agitated conditions. Rag formation occurred for both a cotton wool standard and samples taken from an operating municipal MBR, with between 15% and 75% of the added fibrous material forming a single rag. The extent of rag formation depended both on the material type or origin – lint from laundering operations forming zero rags – and the filament length. Sludging rates were quantified using a bespoke parallel-channel test cell representing the membrane channels of an immersed flat sheet MBR. Sludge samples were provided from two local MBRs, one treating municipal and the other industrial effluent. Bulk sludge properties measured comprised mixed liquor suspended solids (MLSS) concentration, capillary suction time (CST), particle size, soluble COD (sCOD) and rheology (apparent viscosity μₐ vs shear rate γ). The fouling and sludging propensity of the sludge was determined using the test cell, ‘fouling’ being quantified as the pressure incline rate against flux via the flux step test (for which clogging was absent) and sludging by photographing the channel and processing the image to determine the ratio of the clogged to unclogged regions. A substantial difference in rheological and fouling behaviour was evident between the two sludge sources, the industrial sludge having a higher viscosity but less shear-thinning than the municipal. Fouling, as manifested by the pressure increase Δp/Δt, as a function of flux from classic flux-step experiments (where no clogging was evident), was more rapid for the industrial sludge. Across all samples of both sludge origins the expected trend of increased fouling propensity with increased CST and sCOD was demonstrated, whereas no correlation was observed between clogging rate and these parameters. The relative contribution of fouling and clogging was appraised by adjusting the clogging propensity via increasing the MLSS both with and without a commensurate increase in the COD. Results indicated that whereas for the municipal sludge the fouling propensity was affected by the increased sCOD, there was no associated increased in the sludging propensity (or cake formation). The clogging rate actually decreased on increasing the MLSS. Against this, for the industrial sludge the clogging rate dramatically increased with solids concentration despite a decrease in the soluble COD. From this was surmised that sludging did not relate to fouling.

Keywords: clogging, membrane bioreactors, ragging, sludge

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234 Mineralized Nanoparticles as a Contrast Agent for Ultrasound and Magnetic Resonance Imaging

Authors: Jae Won Lee, Kyung Hyun Min, Hong Jae Lee, Sang Cheon Lee

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To date, imaging techniques have attracted much attention in medicine because the detection of diseases at an early stage provides greater opportunities for successful treatment. Consequently, over the past few decades, diverse imaging modalities including magnetic resonance (MR), positron emission tomography, computed tomography, and ultrasound (US) have been developed and applied widely in the field of clinical diagnosis. However, each of the above-mentioned imaging modalities possesses unique strengths and intrinsic weaknesses, which limit their abilities to provide accurate information. Therefore, multimodal imaging systems may be a solution that can provide improved diagnostic performance. Among the current medical imaging modalities, US is a widely available real-time imaging modality. It has many advantages including safety, low cost and easy access for patients. However, its low spatial resolution precludes accurate discrimination of diseased region such as cancer sites. In contrast, MR has no tissue-penetrating limit and can provide images possessing exquisite soft tissue contrast and high spatial resolution. However, it cannot offer real-time images and needs a comparatively long imaging time. The characteristics of these imaging modalities may be considered complementary, and the modalities have been frequently combined for the clinical diagnostic process. Biominerals such as calcium carbonate (CaCO3) and calcium phosphate (CaP) exhibit pH-dependent dissolution behavior. They demonstrate pH-controlled drug release due to the dissolution of minerals in acidic pH conditions. In particular, the application of this mineralization technique to a US contrast agent has been reported recently. The CaCO3 mineral reacts with acids and decomposes to generate calcium dioxide (CO2) gas in an acidic environment. These gas-generating mineralized nanoparticles generated CO2 bubbles in the acidic environment of the tumor, thereby allowing for strong echogenic US imaging of tumor tissues. On the basis of this previous work, it was hypothesized that the loading of MR contrast agents into the CaCO3 mineralized nanoparticles may be a novel strategy in designing a contrast agent for dual imaging. Herein, CaCO3 mineralized nanoparticles that were capable of generating CO2 bubbles to trigger the release of entrapped MR contrast agents in response to tumoral acidic pH were developed for the purposes of US and MR dual-modality imaging of tumors. Gd2O3 nanoparticles were selected as an MR contrast agent. A key strategy employed in this study was to prepare Gd2O3 nanoparticle-loaded mineralized nanoparticles (Gd2O3-MNPs) using block copolymer-templated CaCO3 mineralization in the presence of calcium cations (Ca2+), carbonate anions (CO32-) and positively charged Gd2O3 nanoparticles. The CaCO3 core was considered suitable because it may effectively shield Gd2O3 nanoparticles from water molecules in the blood (pH 7.4) before decomposing to generate CO2 gas, triggering the release of Gd2O3 nanoparticles in tumor tissues (pH 6.4~7.4). The kinetics of CaCO3 dissolution and CO2 generation from the Gd2O3-MNPs were examined as a function of pH and pH-dependent in vitro magnetic relaxation; additionally, the echogenic properties were estimated to demonstrate the potential of the particles for the tumor-specific US and MR imaging.

Keywords: calcium carbonate, mineralization, ultrasound imaging, magnetic resonance imaging

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