Search results for: plasma sprayed coating

Authors: Renata Rank Miranda, Arandi Ginane Bezerra, Ciro Alberto Oliveira Ribeiro, Marco AntôNio Ferreira Randi, Carmen Lúcia Voigt, Lilian Skytte, Kaare Lund Rasmussen, Francisco Filipak Neto, Frank Kjeldsen

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Synergetic and antagonistic effects of drugs are well-known concerns in pharmacological assessments of dose and toxicity. Similar approach should be used in assessing cellular uptake and cytotoxicity of nanoparticles. Since nanoparticles are released into the aquatic environment they may interact with existing xenobiotics. Here we used biochemical assays and quantitative proteomics to assess the cytotoxicity of silver nanoparticles (AgNP) when human hepatoma HepG2 cells were co-exposed to 2 nm AgNP together with either Cd2+ or Hg2+ ions. Time-course experiments (2h, 4h, and 24h) were conducted to assess the first response to the exposure studies. The general trend was that a synergetic toxicological response was observed in cells exposed to both AgNP and Cd2+ or Hg2+, with AgNP and Cd2+ being more toxic. This was observed by a significant increase in the ROS and superoxide level of >35% in the case of AgNP+Cd2+ compared to the sum of responses of AgNP and Cd2+, individually. Metabolic activity and viability also dropped more for AgNP+Cd2+ (>10%) than for AgNP and Cd2+ combined. We used inductively coupled plasma mass spectrometry to investigate if AgNP facilitates larger influx of toxic metal ions into HepG2 cells. Only Hg2+ ions was found to be more efficiently engulfed as the concentration of Hg2+ was found 2.8 times larger compared to exposure experiments with only Hg2+. This effect was not observed for Cd2+. We now continue with deep proteomics studies to obtain wider details on the mechanism of the toxicity related to AgNP, Cd2+, and AgNP+Cd2+, respectively.

Keywords: nanotoxicology, silver nanoparticles, proteomics, human cell line

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Authors: Javier Paul Montalvo Andia, Adriana Larrea Valdivia, Adolfo Pillihuaman Zambrano

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The most common lixiviant in the leaching process of copper minerals is H₂SO₄, however, the current situation requires more environmentally friendly reagents and in certain situations that have a lower consumption due to the presence of undesirable gangue as muscovite or kaolinite that can make the process unfeasible. The present work studied the leaching of an oxidized copper mineral in an aqueous solution of ammonium nitrate, in order to obtain the optimum leaching conditions of the copper contained in the malachite mineral from Peru. The copper ore studied comes from a deposit in southern Peru and was characterized by X-ray diffractometer, inductively coupled-plasma emission spectrometer (ICP-OES) and atomic absorption spectrophotometry (AAS). The experiments were developed in batch reactor of 600 mL where the parameters as; temperature, pH, ammonium nitrate concentration, particle size and stirring speed were controlled according to experimental planning. The sample solution was analyzed for copper by atomic absorption spectrophotometry (AAS). A simulation in the HSC Chemistry 6.0 program showed that the predominance of the copper compounds of a Cu-H₂O aqueous system is altered by the presence in the system of ammonium complexes, the compound being thermodynamically more stable Cu(NH3)₄²⁺, which predominates in pH ranges from 8.5 to 10 at a temperature of 25 °C. The optimum conditions for copper leaching of the malachite mineral were a stirring speed of 600 rpm, an ammonium nitrate concentration of 4M, a particle diameter of 53 um and temperature of 62 °C. These results showed that the leaching of copper increases with increasing concentration of the ammonium solution, increasing the stirring rate, increasing the temperature and decreasing the particle diameter. Finally, the recovery of copper in optimum conditions was above 80%.

Keywords: ammonium nitrate, malachite, copper oxide, leaching

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Authors: Morteza Elsa, Amirhossein Moghanian

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The major aim of this study was to evaluate the effect of CaO content on in vitro hydroxyapatite formation, MC3T3 cells cytotoxicity and proliferation as well as antibacterial efficiency of sol-gel derived SiO₂–CaO–P₂O₅ ternary system. For this purpose, first two grades of bioactive glass (BG); BG-58s (mol%: 60%SiO₂–36%CaO–4%P₂O₅) and BG-68s (mol%: 70%SiO₂–26%CaO–4%P₂O₅)) were synthesized by sol-gel method. Second, the effect of CaO content in their composition on in vitro bioactivity was investigated by soaking the BG-58s and BG-68s powders in simulated body fluid (SBF) for time periods up to 14 days and followed by characterization inductively coupled plasma atomic emission spectrometry (ICP-AES), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM) techniques. Additionally, live/dead staining, 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and alkaline phosphatase (ALP) activity assays were conducted respectively, as qualitatively and quantitatively assess for cell viability, proliferation and differentiations of MC3T3 cells in presence of 58s and 68s BGs. Results showed that BG-58s with higher CaO content showed higher in vitro bioactivity with respect to BG-68s. Moreover, the dissolution rate was inversely proportional to oxygen density of the BG. Live/dead assay revealed that both 58s and 68s increased the mean number live cells which were in good accordance with MTT assay. Furthermore, BG-58s showed more potential antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) bacteria. Taken together, BG-58s with enhanced MC3T3 cells proliferation and ALP activity, acceptable bioactivity and significant high antibacterial effect against MRSA bacteria is suggested as a suitable candidate in order to further functionalizing for delivery of therapeutic ions and growth factors in bone tissue engineering.

Keywords: antibacterial, bioactive glass, hydroxyapatite, proliferation, sol-gel processes

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Authors: Abbas Ahmadi, Nasser Aliasgharzad, Ali Asghar Jafarzadeh

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Nowadays, drying of the Urmia Lake as a largest saline lake in the world and emerging its saline bed from water has caused the risk of salty dune storms, which threats the health of human society and also plants and animal communities living in the region. Biological soil crusts (BSCs) as a dust stabilizer attracted the attention of Soil conservation experts in recent years. Although the presence of water by the impenetrable lake bed and endorheic basin can be an advantage to create BSCs, but the extraordinary of the lake bed salinity is a factor for prevention of its establishment in the region. Therefore, the present research work has been carried out to investigate the effects of inoculating the Cyanobacteria, algae and their combination to create BSCs for dust control. In this study, an algae attributed to Chlamydomonas sp and a cyanobacteria attributed to Anabaena sp isolated from the soils of Urmia Lake margin were used to create BSC in four soil samples which collected from 0-10 cm of the current margin (A), the previous bed (B), affected lands by lake (C) and Quomtappe sand dune (D). The main characteristics of the A, B and C soil samples are their highly salinity (their ECe are 108, 140 and 118 dS/m, respectively) and sodicity. Also, texture class of the soil A was loamy sand, and other two soils had clay textures. Soil D was Non-saline, but it was sodic with a sandy texture class. This study was conducted separately in each soil in a completely randomized design under four inoculation treatments of non-inoculated (T0), Algae (T1), cyanobacteria (T2) and equal mixture of algae and cyanobacteria (T3) with three replications. In the experiment, the soil was placed into wind tunnel trays, and a suspension containing microorganisms mixed with the trays surface soil. During the experiment, water was sprayed to the trays at the morning and evening of every day. After passing the incubation period (30 days), some characteristics of samples such as pH, EC, cold water extractable carbohydrate (CWEC), hot water extractable carbohydrate (HWEC), sulfuric acid extractable carbohydrate (SAEC), organic matter, crust thickness, penetration resistance, wind erosion threshold velocity and soil loss in the wind tunnel were measured, and Correlation between the measured characteristics was obtained through the SPSS software. Analysis of variance and so comparison between the means of treatments were analyzed with MSTATC software. In this research, Chlorophyll, an amount, was used as an indicator of the microorganism's population in the samples. Based on obtained results, the amount of Chlorophyll a in the T2 treatment of soil A and all treatments of soil D was significantly increased in comparison to the control and crust thickness showed increase in all treatments by microorganism’s inoculation. But effect of the treatments was significant in soils A and D. At all treatment’s inoculation of microorganisms in soil A caused to increase %46, %34 and %55 of the wind erosion threshold velocity in T1, T2 and T3 treatments in comparison to the control, respectively, and in soil D all treatments caused wind erosion threshold velocity became two times more than control. However, soil loss in the wind tunnel experiments was significant in T2 and T3 treatments of these soils and T1 treatment had no effect in reducing soil loss. Correlation between Chlorophyll a and salinity shows the important role of salinity in microbial growth prevention and formation of BSCs in the studied samples. In general, according to the obtained results, it can be concluded that salinity reduces the growth of microorganisms in saline soils of the region, and in soils with fine textures, salinity role in prevention of the microbial growth is clear. Also, using the mix of algae and cyanobacteria together caused the synergistic growth of them and consequently, better protection of the soil against wind erosion was provided.

Keywords: wind erosion, algae, cyanobacteria, carbohydrate

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Authors: Mohamed I. D. Helal, Mohamed M. El-Mogy, Hassan A. Khater, Muhammad A. Fathy, Fatma E. Ibrahim, Yuncong C. Li, Zhaohui Tong, Karima F. Abdelgawad

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Minimizing the consumption of agrochemicals, particularly nitrogen, is the ultimate goal for achieving sustainable agricultural production with low cost and high economic and environmental returns. The use of biopolymers instead of petroleum-based synthetic polymers for CRFs can significantly improve the sustainability of crop production since biopolymers are biodegradable and not harmful to soil quality. Lignin is one of the most abundant biopolymers that naturally exist. In this study, controlled-release fertilizers were developed using a biobased nanocomposite of lignin and bentonite clay mineral as a coating material for urea to increase nitrogen use efficiency. Five types of controlled-release urea (CRU) were prepared using two ratios of modified bentonite as well as techniques. The efficiency of the five controlled-release nano-urea (CRU) fertilizers in improving the growth of tomato plants was studied under field conditions. The CRU was applied to the tomato plants at three N levels representing 100, 50, and 25% of the recommended dose of conventional urea. The results showed that all CRU treatments at the three N levels significantly enhanced plant growth parameters, including plant height, number of leaves, fresh weight, and dry weight, compared to the control. Additionally, most CRU fertilizers increased total yield and fruit characteristics (weight, length, and diameter) compared to the control. Additionally, marketable yield was improved by CRU fertilizers. Fruit firmness and acidity of CRU treatments at 25 and 50% N levels were much higher than both the 100% CRU treatment and the control. The vitamin C values of all CRU treatments were lower than the control. Nitrogen uptake efficiencies (NUpE) of CRU treatments were 47–88%, which is significantly higher than that of the control (33%). In conclusion, all CRU treatments at an N level of 25% of the recommended dose showed better plant growth, yield, and fruit quality of tomatoes than the conventional fertilizer.

Keywords: nitrogen use efficiency, quality, urea, nano particles, ecofriendly

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Authors: Leelavinothan Pari , Ayyasamy Rathinam

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Diabetes mellitus (DM) is a major and growing public health problem throughout the world. Pterocarpus marsupium (Roxb.) (Family: Fabaceae) is widely used as a traditional medicine to treat various diseases including diabetes. However, the molecular mechanism of Pterocarpus marsupium has not been investigated so far. Two fractions (2.5% and 5%) of extract from the medicinal plant, Pterocarpus marsupium (PME) were conducted in a dose dependent manner in streptozotocin (45 mg/kg b.w.) induced type 2 diabetic rats. Each fraction of PME was administered to diabetic rats intragastrically at a dose of 50, 100 and 200 mg/kg b.w for 45 days. The effective dose 200 mg/kg b.w of 5% fraction was more pronounced in reducing the levels of blood glucose (95.65 mg/dL) and glycosylated hemoglobin (HbA1c) (0.41 mg/g Hb), and increasing the plasma insulin (16.20 µU/mL) level. Moreover, PME (200 mg/kg b.w) significantly ameliorated lipid peroxidation products (thiobarbituric reactive substances, lipid hydroperoxides) enzymatic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymatic antioxidants (Vitamin C, Vitamin E and reduced glutathione) levels. The altered activities of the key enzymes of lipid metabolism along with the lipid profile in diabetic rats were significantly reverted to near normal levels by the administration of PME 5% 200 mg/kg b.w fraction. PME (200 mg/kg b.w) has the ability to reduce the inflammatory cytokines, such as TNF-α, IL-6 mRNA, as well as protein expression and apoptotic marker, such as caspase-3 enzyme in diabetic hepatic tissue. The above biochemical findings were also supported by histological studies such as improvement in pancreas and liver. Pterocarpus marsupium could effectively reduce the hyperglycemia, oxidative-stress, inflammation and hyperlipedimea in diabetic rats; hence it could be a useful drug in the management of diabetes without any side effects.

Keywords: diabetes mellitus, streptozotocin, Pterocarpus marsupium, lipid peroxidation, Antioxidants, inflammatory cytokines

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Authors: Muhammad Naeem, Juho Lee, Jin-Wook Yoo

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In this study, we hypothesized that prolonged gastrointestinal transit at the inflamed colon conferred by a pH-triggered mucoadhesive smart nanoparticulate drug delivery system aids in achieving selective and sustained levels of the drug within the inflamed colon for the treatment of ulcerative colitis. We developed budesonide-loaded pH-sensitive charge-reversal solid lipid nanoparticles (SLNs) using a hot homogenization method. Polyetylenimine (PEI) was used to render SLNs cationic (PEI-SLNs). Eudragit S100 (ES) was coated on PEI-SLNs for pH-trigger charge-reversal SLNs (ES-PEI-SLNs). Therapeutic potential of the prepared SNLs formulation was evaluated in ulcerative colitis in mice. The transmission electron microscopy, zeta size and zeta potential data showed the successful formation of SLNs formulations. SLNs and PEI-SLNs showed burst drug release in acidic pH condition mimicking stomach and early small intestine environment which limiting their application as oral delivery systems. However, ES-PEI-SLNs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. Most importantly, the surface charge of ES-PEI-SLNs switched from negative to positive in colonic conditions by pH-triggered removal of ES coating and accumulated selectively in inflamed colon. Furthermore, a charge reversal ES-PEI-SLNs showed a superior mitigation of dextran sulfate sodium (DSS)-induced acute colitis in mice as compared to SLNs and PEI-SLNs treated groups. Moreover, histopathological analysis of distal colon sections stained with hematoxylin/eosin and E-cadherin immunostaining revealed attenuated inflammation in an ES-PEI-SLNs-treated group. We also found that ES-PEI-SLNs markedly reduced the myeloperoxidase level and expression of TNF-alpha in colon tissue. Our results suggest that the pH-triggered charge reversal SLNs presented in this study would be a promising approach for ulcerative colitis therapy.

Keywords: solid lipid nanoparticles, stimuli-triggered charge-reversal, ulcerative colitis, methacrylate copolymer, budesonide

Procedia PDF Downloads 226

Authors: Alireza Arab, Morteza Elsa, Amirhossein Moghanian

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In this study, experiments were carried out to achieve a promising multifunctional and modified silicate based bioactive glass (BG). The main aim of the study was investigating the effect of lithium (Li) and magnesium (Mg) substitution, on in vitro bioactivity of substituted-58S BG. Moreover, it is noteworthy to state that modified BGs were synthesized in 60SiO₂–(36-x)CaO–4P₂O₅–(x)Li₂O and 60SiO₂–(36-x)CaO–4P₂O₅–(x)MgO (where x = 0, 5, 10 mol.%) quaternary systems, by sol-gel method. Their performance was investigated through different aspects such as biocompatibility, antibacterial activity as well as their effect on alkaline phosphatase (ALP) activity, and proliferation of MC3T3 cells. The antibacterial efficiency was evaluated against methicillin-resistant Staphylococcus aureus bacteria. To do so, CaO was substituted with Li₂O and MgO up to 10 mol % in 58S-BGs and then samples were immersed in simulated body fluid up to 14 days and then, characterized by X-ray diffraction, Fourier transform infrared spectroscopy, inductively coupled plasma atomic emission spectrometry, and scanning electron microscopy. Results indicated that this modification led to a retarding effect on in vitro hydroxyapatite (HA) formation due to the lower supersaturation degree for nucleation of HA compared with 58s-BG. Meanwhile, magnesium revealed further pronounced effect. The 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and ALP analysis illustrated that substitutions of both Li₂O and MgO, up to 5 mol %, had increasing effect on biocompatibility and stimulating proliferation of the pre-osteoblast MC3T3 cells in comparison to the control specimen. Regarding to bactericidal efficiency, the substitution of either Li or Mg for Ca in the 58s BG composition led to statistically significant difference in antibacterial behaviors of substituted-BGs. Meanwhile, the sample containing 5 mol % CaO/Li₂O substitution (BG-5L) was selected as a multifunctional biomaterial in bone repair/regeneration due to the improved biocompatibility, enhanced ALP activity and antibacterial efficiency among all of the synthesized L-BGs and M-BGs.

Keywords: alkaline, alkaline earth, bioactivity, biomedical applications, sol-gel processes

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Authors: Awan A. Zaima, Tanvieer Ayesha, Mirshahi Shahsoltan, Pocard Marc, Mirshahi Massoud

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Brain-derived neurotrophic factor (BDNF) is described as a factor helping to support the survival of existing neurons by involving the growth and differentiation of new neurons and synapses. Cancer diagnosis impacts the mental health, and in consequences, depression arise eventually hinders recovery and disrupts the quality of life and surviving chances of patients. The focus of this study is to hint upon a prospective biomarker as a promising diagnostic tool for an early indicator/predictor of depression prevalence in cancer patients for better care and treatment options. The study aims to analyze peripheral biomarkers from neuro immune axis (BDNF, IL21 as a NK cell activator) using co-relation approach. Samples were obtained from random non cancer candidates and advanced peritoneum carcinomatosis patients with 25% pseudomyxoma, 21% Colon cancer,19% stomach cancer, 10% ovarian cancer, 8% appendices cancer, and 10% other area of peritoneum cancer patients. Both groups of the study were categorized by gender and age, with a range of 18 to 86 years old. Biomarkers were analyzed in collected plasma by performing multiplex sandwich ELISA system. Data were subjected to statistical analysis for the assessment of the correlation. Our results demonstrate that BNDF and IL 21 down regulated significantly in patient groupas compared to non-cancer candidates (ratio of patients/normalis 2.57 for BNDF and 1.32 for IL21). This preliminary investigation suggested that the neuro immune biomarkers are down regulated in carcinomatosis patients and can be associated with cancer expansion and cancer genesis. Further studies on larger cohort are necessary to validate this hypothesis.

Keywords: biomarkers, depression, peritoneum carcinoma, BNDF, IL21

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Authors: Adela Penesova, Zofia Radikova, Boris Bajer, Andrea Havranova, Miroslav Vlcek

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Background: The aim of our study was to compare the effect of intensified lifestyle intervention on insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Fibroblast growth factor (FGF) 21 after 8 weeks of lifestyle intervention. Methods: A group of 43 obese patients (13M/30F; 43.0±12.4 years; BMI (body mass index) 31.2±6.3 kg/m2 participated in a weight loss interventional program (NCT02325804) following an 8-week hypocaloric diet (-30% energy expenditure) and physical activity 150 minutes/week. Insulin sensitivity was evaluated according to the homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity indices according to Matsuda and Cederholm were calculated (ISImat and ISIced). Plasma ALT, AST, Fetuin-A, FGF 21, and physical fitness were measured. Results: The average reduction of body weight was 6.8±4.9 kg (0-15 kg; p=0.0006), accompanied with a significant reduction of body fat amount of fat mass (p=0.03), and waist circumference (p=0.02). Insulin sensitivity has been improved (IR HOMA 2.71±3.90 vs 1.24±0.83; p=0.01; ISIMat 6.64±4.38 vs 8.93±5.36 p ≤ 0.001). Total, LDL cholesterol, and triglycerides decreased (p=0.05, p=0.04, p=0.04, respectively). Physical fitness significantly improved after intervention (as measure VO2 max (maximal oxygen uptake) (p ≤ 0.001). ALT decreased significantly (0.44±0.26 vs post 0.33±0.18 ukat/l, p=0.004); however, AST not (pre 0.40±0.15 vs 0.35±0.09 ukat/l, p=0.07). Hepatokine Fetuin-A significantly decreased after intervention (43.1±10.8 vs 32.6±8.6 ng/ml, p < 0.001); however, FGF 21 levels tended to decrease (146±152 vs 132±164 pg/ml, p=0.07). Conclusion: 8-weeks of diet and physical activity intervention program in obese otherwise healthy subjects led to an improvement of insulin resistance parameters and liver marker profiles, as well as increased physical fitness. This study was supported by grants APVV 15-0228; VEGA 2/0161/16.

Keywords: obesity, diet, exercice, insulin sensitivity

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Authors: Mark Bezner, Shani Deri, Tom Trigano, Kfir Ben-Harush

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Intermediate filament (IF) proteins-based fibers are among the toughest fibers in nature, as was shown by native hagfish slime threads and by synthetic fibers that are based on type V IF-proteins, the nuclear lamins. It is assumed that their mechanical performance stems from two major factors: (1) the transition from elastic -helices to stiff-sheets during tensile load; and (2) the specific organization of the coiled-coil proteins into a hierarchical network of nano-filaments. Here, we investigated the interrelationship between these two factors by using wet-spun fibers based on C. elegans (Ce) lamin. We found that Ce-lamin fibers, whether assembled in aqueous or alcoholic solutions, had the same nonlinear mechanical behavior, with the elastic region ending at ~5%. The pattern of the transition was, however, different: the ratio between -helices and -sheets/random coils was relatively constant until a 20% strain for fibers assembled in an aqueous solution, whereas for fibers assembled in 70% ethanol, the transition ended at a 6% strain. This structural phenomenon in alcoholic solution probably occurred through the transition between compacted and extended conformation of the random coil, and not between -helix and -sheets, as cycle analyses had suggested. The different transition pattern can also be explained by the different higher order organization of Ce-lamins in aqueous or alcoholic solutions, as demonstrated by introducing a point mutation in conserved residue in Ce-lamin gene that alter the structure of the Ce-lamins’ nano-fibrils. In addition, biomimicking the layered structure of silk and hair fibers by coating the Ce-lamin fiber with a hydrophobic layer enhanced fiber toughness and lead to a reversible transition between -helix and the extended conformation. This work suggests that different hierarchical structures, which are formed by specific assembly conditions, lead to diverse secondary structure transitions patterns, which in turn affect the fibers’ mechanical properties.

Keywords: protein-based fibers, intermediate filaments (IF) assembly, toughness, structure-property relationships

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Authors: Mahsa Ahmadi, Mehdi Mehdikhani-Nahrkhalaji, Jaleh Varshosaz, Shadi Farsaei

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Gelatin and hyaluronic acid are commonly used in skin tissue engineering scaffolds, but because of their low mechanical properties and high biodegradation rate, adding a synthetic polymer such as polycaprolactone could improve the scaffold properties. Therefore, we developed a gelatin-hyaluronic acid-polycaprolactone scaffold, containing 0.5 % atorvastatin loaded nanostructured lipid carriers (NLCs) for skin tissue engineering. The atorvastatin loaded NLCs solution was prepared by solvent evaporation method and freeze drying process. Synthesized atorvastatin loaded NLCs was added to the gelatin and hyaluronic acid solution, and a membrane was fabricated with solvent evaporation method. Thereafter it was coated by a thin layer of polycaprolactone via spine coating set. The resulting scaffolds were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses. Moreover, mechanical properties, in vitro degradation in 7 days period, and in vitro drug release of scaffolds were also evaluated. SEM images showed the uniform distributed NLCs with an average size of 100 nm in the scaffold structure. Mechanical test indicated that the scaffold had a 70.08 Mpa tensile modulus which was twofold of tensile modulus of normal human skin. A Franz-cell diffusion test was performed to investigate the scaffold drug release in phosphate buffered saline (pH=7.4) medium. Results showed that 72% of atorvastatin was released during 5 days. In vitro degradation test demonstrated that the membrane was degradated approximately 97%. In conclusion, suitable physicochemical and biological properties of membrane indicated that the developed gelatin-hyaluronic acid-polycaprolactone nanocomposite scaffold containing 0.5 % atorvastatin loaded NLCs could be used as a good candidate for skin tissue engineering applications.

Keywords: atorvastatin, gelatin, hyaluronic acid, nano lipid carriers (NLCs), polycaprolactone, skin tissue engineering, solvent casting, solvent evaporation

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Authors: Claire B. Salvedia, Enrico P. Supangco, Francisco B. Eligado, Renato Sa Vega, Antonio A. Rayos

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The study was conducted to evaluate the effect of probiotic feeding on weight gain, blood biochemical and hematological indices of crossbred dairy goat kids. Sixteen (16) crossbred Anglo-Nubian x Saanen dairy goat kids, 3 to 4 months old, ranging from 19 to 23kg were randomly assigned into four treatments fed with 5x109 cfu/ml probiotic supplements; Treatment 1 – control; Treatment 2 – lactic acid bacteria (L. plantarum BS and P. acidilactici 3G3); treatment 3 – S. cerevisiae 2030; Treatment 4 – multi-strain probiotics (L. plantarum BS, P. acidilactici 3G3, and S.cerevisiae 2030). Feed ration provided daily for each of the experimental animals were composed of 1kg mixed concentrate feed ((Leucaena leucocephala dried leaves and pollard), and 4 kg fresh Pennisetum purpureum and Gliciridia sepium leaves (50:50). The experimental feeding trial lasted for 9 weeks. Result revealed that treatments fed with probiotics had significantly (P≤0.05) higher weight gain compared to the control. Significant effect on plasma urea nitrogen (PUN) and triglyceride were noted during 30th and 60th day of probiotic feeding. White blood cell counts were significantly affected by probiotic feeding during the 60th day. Concentrations of glucose and cholesterol remained unchanged throughout the experimental period. The findings suggests, under the condition of the experiment, that live probiotic feeding could have a significant role in improving weight gain and metabolism of crossbred dairy goat kids.

Keywords: probiotics, weight gain, blood biochemical indices, crossbred dairy goat kids

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Authors: Somaiya Mateen, Shagufta Moin, Mohammad Owais, Abdul Khan, Atif Zafar

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In rheumatoid arthritis (RA), impaired oxidative metabolism and imbalance between pro-and anti-inflammatory cytokines are responsible for causing inflammation and the degradation of cartilage and bone. The present study was done to evaluate the level and hence the role of reactive oxygen species (ROS) and inflammatory cytokines in the pathogenesis of RA. The present study was performed in the blood of 80 RA patients and 55 age and sex-matched healthy controls. The level of ROS (in 5% hematocrit) and the plasma level of pro-inflammatory cytokines [TNF-α, interleukin-6 (IL-6), IL-22] and anti-inflammatory cytokines (IL-4 and IL-5) were monitored in healthy subjects and RA patients. For evaluating the role of rheumatoid factor (RF) in the pathogenesis of RA, patients were sub-divided on the basis of presence or absence of RF. Reactive species and inflammatory cytokines were correlated with disease activity measure-Disease Activity Score for 28 joints (DAS28). The level of ROS, TNF-α, IL-6 and IL-22 were found to be significantly higher in RA patients as compared to the healthy controls, with the increase being more significant in patients positive for rheumatoid factor and those having high disease severity. On the other hand, a significant decrease in the level of IL-4 and IL-10 were observed in RA patients compared with healthy controls, with the decrease being more prominent in severe cases of RA. Higher ROS (indicative of impaired anti-oxidant defence system) and pro-inflammatory cytokines level in RA patients may lead to the damage of biomolecules which in turn contributes to tissue damage and hence to the development of more severe RA. The imbalance between pro-and anti-inflammatory cytokines may lead to the development of multi-system immune complications. ROS and inflammatory cytokines may also serve as a potential biomarker for assessing the disease severity.

Keywords: rheumatoid arthritis, reactive oxygen species, pro-inflammatory cytokines, anti-inflammatory cytokines

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Authors: Austin Jiang, Richard M. Salmon, Nicholas W. Morrell, Wei Li

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BMP10 is highly expressed in the developing heart and plays essential roles in cardiogenesis. BMP10 deletion in mice results in embryonic lethality due to impaired cardiac development. In adults, BMP10 expression is restricted to the right atrium, though ventricular hypertrophy is accompanied by increased BMP10 expression in a rat hypertension model. However, reports of BMP10 activity in the circulation are inconclusive. In particular it is not known whether in vivo secreted BMP10 is active or whether additional factors are required to achieve its bioactivity. It has been shown that high-affinity binding of the BMP10 prodomain to the mature ligand inhibits BMP10 signaling activity in C2C12 cells, and it was proposed that prodomain-bound BMP10 (pBMP10) complex is latent. In this study, we demonstrated that the BMP10 prodomain did not inhibit BMP10 signaling activity in multiple endothelial cells, and that recombinant human pBMP10 complex, expressed in mammalian cells and purified under native conditions, was fully active. In addition, both BMP10 in human plasma and BMP10 secreted from the mouse right atrium were fully active. Finally, we confirmed that active BMP10 secreted from mouse right atrium was in the prodomain-bound form. Our data suggest that circulating BMP10 in adults is fully active and that the reported vascular quiescence function of BMP10 in vivo is due to the direct activity of pBMP10 and does not require an additional activation step. Moreover, being an active ligand, recombinant pBMP10 may have therapeutic potential as an endothelial-selective BMP ligand, in conditions characterized by loss of BMP9/10 signaling.

Keywords: bone morphogenetic protein 10 (BMP10), endothelial cell, signal transduction, transforming growth factor beta (TGF-B)

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Authors: Devadrita Dey Sarkar

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Oxidosqualene cyclase is a membrane bound enzyme in which helps in the formation of steroid scaffold in higher organisms. In a highly selective cyclization reaction oxidosqualene cyclase forms LANOSTEROL with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. In humans OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. The enzyme oxidosqualene: lanosterol cyclase (OSC) represents a novel target for the treatment of hypercholesterolemia. OSC catalyzes the cyclization of the linear 2,3-monoepoxysqualene to lanosterol, the initial four-ringed sterol intermediate in the cholesterol biosynthetic pathway. OSC also catalyzes the formation of 24(S), 25-epoxycholesterol, a ligand activator of the liver X receptor. Inhibition of OSC reduces cholesterol biosynthesis and selectively enhances 24(S),25-epoxycholesterol synthesis. Through this dual mechanism, OSC inhibition decreases plasma levels of low-density lipoprotein (LDL)-cholesterol and prevents cholesterol deposition within macrophages. The recent crystallization of OSC identifies the mechanism of action for this complex enzyme, setting the stage for the design of OSC inhibitors with improved pharmacological properties for cholesterol lowering and treatment of atherosclerosis. While studying and designing the inhibitor of oxidosqulene cyclase, I worked on the pdb id of 1w6k which was the most worked on pdb id and I used several methods, techniques and softwares to identify and validate the top most molecules which could be acting as an inhibitor for oxidosqualene cyclase. Thus, by partial blockage of this enzyme, both an inhibition of lanosterol and subsequently cholesterol formation as well as a concomitant effect on HMG-CoA reductase can be achieved. Both effects complement each other and lead to an effective control of cholesterol biosynthesis. It is therefore concluded that 2,3-oxidosqualene cyclase plays a crucial role in the regulation of intracellular cholesterol homeostasis. 2,3-Oxidosqualene cyclase inhibitors offer an attractive approach for novel lipid-lowering agents.

Keywords: anticholesteraemic, crystallization, statins, homeostasis

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Authors: Anupam Chanda

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Presently Packaging plays a significant role for drug discoveries. The process of selecting materials and the type of packaging also offers an opportunity for the Packaging scientist to look for biological delivery choices. Most injectable protein products were supplied in some sort of glass vial, prefilled syringe, cartridge. Those product having high Ph content there is a chance of “delamination “from inner surface of glass vial. With protein-based drugs, the biggest issue is the effect of packaging derivatives on the protein’s threedimensional and surface structure. These are any effects that relate to denaturation or aggregation of the protein due to oxidation or interactions from contaminants or impurities in the preparation. The potential for these effects needs to be carefully considered in choosing the container and the container closure system to avoid putting patients in jeopardy. Cause of Delamination : -Formulations with a high pH include phosphate and citrate buffers increase the risk of glass delamination. -High alkali content in glass could accelerate erosion. -High temperature during the vial-forming process increase the risk of glass delamination. -Terminal sterilization (irradiated at 20-40 kGy for 150 min) also is a risk factor for specific products(veterinary parenteral administration),could cause delamination. -High product-storage temperatures and long exposure times can increase the rate and severity of glass delamination. How to prevent Delamination -Treating the surface of the glass vials with materials, such as ammonium sulfate or siliconization can reduce the rate of glass erosion. -Consider alternative sterilization methods only in rare cases. -The correct specification for the glass to ensure its suitability for the pH of the product. -Use Cyclic olefin copolymer(COC)/Cyclic olefin Polymer(COP) Adsorption of protein and Solutions: Option#1 Coat with linear methoxylated polyglycerol and hyperbranchedmethoxylated polyglycerol. Option#2 Thehyperbranched non-methoxylated coating performed best. Option#3 Coat with hyperbranched polyglycerol Option#4 Right selection of Sterilization of glass vial/syringe.

Keywords: delamination of glass, ptrotien adoptions inside the glass surface, extractable & leachable solutions, injectable designs for new drugs

Procedia PDF Downloads 75

Authors: Nthabiseng Portia Mahumapelo, Andre van Niekerk, Ndabenhle Sosibo, Nirdesh Singh

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The foundry industry generates large quantities of solid waste in the form of waste foundry sand. The ever-increasing quantities of this type of industrial waste put pressure on land-filling space and its proper management has become a global concern. The South African foundry industry is not different when it comes to this solid waste generation. Utilizing the foundry waste sand in other applications has become an attractive avenue to deal with this waste stream. In the present paper, an evaluation was done on the suitability of foundry waste sand as an additive in clay masonry products. Purchased clay was added to the foundry waste sand sample in a 50/50 ratio. The mixture was named FC sample. The FC sample was mixed with water in a pan mixer until the mixture was consistent and suitable for extrusion. The FC sample was extruded and cut into briquettes. Water absorption, shrinkage and modulus of rupture tests were conducted on the resultant briquettes. Foundry waste sand and FC samples were respectively characterized mineralogically using X-Ray Diffraction, and the major and trace elements were determined using Inductively Coupled Plasma Optical Emission Spectroscopy. Adding purchased clay to the foundry waste sand positively influenced the workability of the test sample. Another positive characteristic was the low linear shrinkage, which indicated that products manufactured from the FC sample would not be susceptible to cracking. The water absorption values were acceptable and the unfired and fired strength values of the briquette’s samples were acceptable. In conclusion, tests showed that foundry waste sand can be used as an additive in masonry clay bricks, provided it is blended with good quality clay.

Keywords: foundry waste sand, masonry clay bricks, modulus of rupture, shrinkage

Procedia PDF Downloads 192

Authors: Tarek Elnimr, Rabab El-kelany

Abstract:

Heavy metals are environmental contaminants that may pose long-term health risks. Unfortunately, the consequent implementation of preventive measures was generally delayed, causing important negative effects to the exposed populations. The objective of this study was to determine whether co-consumption of nutritional supplements as selenium and vitamin E would treat the hazardous effects of exposure to mercury, lead and cadmium. 108 workers (60 males and 48 females) were the subject of this study, their ages ranged from 19-63 years, (M = 29.5±10.12). They were working in lamp factory for an average of 0.5-40 years (M= 5.3±8.8). Twenty control subjects matched for age and gender were used for comparison. All workers were subjected to neuropsychiatric evaluation. General Health Questionnaire (GHQ-28) revealed that 44.4% were complaining of anxiety, 52.7% of depression, 41.6% of social dysfunction and 22.2% of somatic symptoms. Cognitive tests revealed that long-term memory was not affected significantly when compared with controls, while short term memory and perceptual ability were affected significantly. Blood metal levels were measured by Inductively Coupled Plasma – optical emission spectrometry(ICP-OES), and revealed that the mean blood mercury, lead and cadmium concentrations before treatment were 1.6 mg/l, 0.39 mg/l and 1.7 µg/l, while they decreased significantly after treatment to 1.2 mg/l, 0.29 mg/l and 1.3 µg/l respectively. Anti-oxidative enzymes (paraoxonase and catalase) and lipid peroxidation product (malondialdehyde) were measured before and after treatment with selenium and vitamin E, and showed significant improvement. It could be concluded that co-consumption of selenium and vitamin E produces significant decrease in mercury, lead and cadmium levels in blood.

Keywords: mercury, lead, cadmium, neuropsychiatric impairment, selenium, vitamin E

Procedia PDF Downloads 317

Authors: Chinedu F. Anochie

Abstract:

The deterioration of materials as a result of their interaction with the environment has been a huge challenge to engineering. Many steps have been taking to tackle corrosion and its effects on harmful effects on engineering materials and structures. Corrosion inhibition, coating, passivation, materials selection, and cathodic protection are some of the methods utilized to curtail the rate at which materials corrode. The use of sacrificial anodes (magnesium, aluminum, or zinc) to protect the metal of interest is a widespread technique used to prevent corrosion in underground structures, ship hauls, and other structures susceptible to corrosion attack. However, certain factors, like resistivity, affect the performance of sacrificial anodes. To establish the effect of soil resistivity on the effectiveness of a cathodic protection system, a mild steel specimen was cathodically protected around Workshop 2 area, Federal University of Technology, Owerri, Nigeria. Design calculations showed that one zinc anode was sufficient to protect the pipe. The specimen (mild steel pipe) was coated with white and black polykene tapes and was subsequently buried in a high resistivity soil. The pipe-to-soil potential measurements were obtained using a digital fluke multimeter. The protection potential obtained on installation was higher than the minimum protection criteria. However, the potential results obtained over a fourteen-day intervals continually decreased to a value significantly lower than the minimum protection criteria. This showed that the sacrificial anode (zinc) was rendered ineffective by the high resistivity of the area of installation. It has been shown that the resistivity of the soil has a marked effect on the feasibility of cathodic protection systems. This work justified that zinc anode cannot be used for cathodic protection around Workshop 2 area, Federal University of Technology, Owerri, Nigeria, because of the high resistivity of the area. An experimental data which explains the effectiveness of galvanic anode cathodic protection system on corrosion control of a small steel structure, exposed to a soil of high resistivity has been established.

Keywords: cathodic protection, corrosion, pipe, sacrificial anode

Procedia PDF Downloads 150

Authors: Stanisław Fic, Danuta Barnat-Hunek, Przemysław Brzyski

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The aim of the study was to evaluate the possibility of applying modified lime binder together with natural flax fibers and straw to the production of wall blocks to the usage in energy-efficient construction industry and the development of proposals for technological solutions. The following laboratory tests were performed: the analysis of the physical characteristics of the tested materials (bulk density, total porosity, and thermal conductivity), compressive strength, a water droplet absorption test, water absorption of samples, diffusion of water vapor, and analysis of the structure by using SEM. In addition, the process of surface hydrophobisation was analyzed. In the paper, there was examined the effectiveness of two formulations differing in the degree of hydrolytic polycondensation, viscosity and concentration, as these are the factors that determine the final impregnation effect. Four composites, differing in composition, were executed. Composites, as a result of the presence of flax straw and fibers showed low bulk density in the range from 0.44 to 1.29 kg/m3 and thermal conductivity between 0.13 W/mK and 0.22 W/mK. Compressive strength changed in the range from 0,45 MPa to 0,65 MPa. The analysis of results allowed observing the relationship between the formulas and the physical properties of the composites. The results of the effectiveness of hydrophobisation of composites after 2 days showed a decrease in water absorption. Depending on the formulation, after 2 days, the water absorption ratio WH of composites was from 15 to 92% (effectiveness of hydrophobization was suitably from 8 to 85%). In practice, preparations based on organic solvents often cause sealing of surface, hindering the diffusion of water vapor from materials but studies have shown good water vapor permeability by the hydrophobic silicone coating. The conducted pilot study demonstrated the possibility of applying flax composites. The article shows that the reduction of CO2 which is produced in the building process can be affected by using natural materials for the building components whose quality is not inferior as compared to the materials which are commonly used.

Keywords: ecological construction, flax fibers, hydrophobisation, lime

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Authors: Violina R. Angelova

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Comparative research has been conducted to allow us to determine the content of macro and microelements in the vegetative and reproductive organs of grass pea and the quality of grass pea seeds, as well as to identify the possibility of grass pea growth on soils contaminated by heavy metals. The experiment was conducted on an agricultural field subjected to contamination from the Non-Ferrous-Metal Works (MFMW) near Plovdiv, Bulgaria. The experimental plots were situated at different distances of 0.5 km and 8 km, respectively, from the source of pollution. On reaching commercial ripeness the grass pea plants were gathered. The composition of the macro and microelements in plant materials (roots, stems, leaves, seeds), and the dry matter content, sugars, proteins, fats and ash contained in the grass pea seeds were determined. Translocation factors (TF) and bioaccumulation factor (BCF) were also determined. The quantitative measurements were carried out through inductively-coupled plasma (ICP). The grass pea plant can successfully be grown on soils contaminated by heavy metals. Soil pollution with heavy metals does not affect the quality of the grass pea seeds. The seeds of the grass pea contain significant amounts of nutrients (K, P, Cu, Fe Mn, Zn) and protein (23.18-29.54%). The distribution of heavy metals in the organs of the grass pea has a selective character, which reduces in the following order: leaves > roots > stems > seeds. BCF and TF values were greater than one suggesting efficient accumulation in the above ground parts of grass pea plant. Grass pea is a plant that is tolerant to heavy metals and can be referred to the accumulator plants. The results provide valuable information about the chemical and nutritional composition of the seeds of the grass pea grown on contaminated soils in Bulgaria. The high content of macro and microelements and the low concentrations of toxic elements in the grass pea grown in contaminated soil make it possible to use the seeds of the grass pea as animal feed.

Keywords: Lathyrus sativus L, macroelements, microelements, quality

Procedia PDF Downloads 106

Authors: Solange Adechian, Michèle Balage, Didier Remond, Carole Migné, Annie Quignard-Boulangé, Agnès Marset-Baglieri, Sylvie Rousset, Yves Boirie, Claire Gaudichon, Dominique Dardevet, Laurent Mosoni

Abstract:

Studies have shown that timing of protein intake, leucine content, and speed of digestion significantly affect postprandial protein utilization. Our aim was to determine if one can spare lean body mass during energy restriction by varying the quality and the timing of protein intake. Obese volunteers followed a 6-wk restricted energy diet. Four groups were compared: casein pulse, casein spread, milk-soluble protein (MSP, = whey) pulse, and MSP spread (n = 10-11 per group). In casein groups, caseins were the only protein source; it was MSP in MSP groups. Proteins were distributed in four meals per day in the proportion 8:80:4:8% in the pulse groups; it was 25:25:25:25% in the spread groups. We measured weight, body composition, nitrogen balance, 3-methylhistidine excretion, perception of hunger, plasma parameters, adipose tissue metabolism, and whole body protein metabolism. Volunteers lost 7.5 ± 0.4 kg of weight, 5.1 ± 0.2 kg of fat, and 2.2 ± 0.2 kg of lean mass, with no difference between groups. In adipose tissue, cell size and mRNA expression of various genes were reduced with no difference between groups. Hunger perception was also never different between groups. In the last week, due to a higher inhibition of protein degradation and despite a lower stimulation of protein synthesis, postprandial balance between whole body protein synthesis and degradation was better with caseins than with MSP. It seems likely that the positive effect of caseins on protein balance occurred only at the end of the experiment.

Keywords: lean body mass, fat mass, casein, whey, protein metabolism

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Authors: Abraham Addo-Bediako, Sophy Nukeri, Tebatso Mmako

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Many freshwater ecosystems have been subjected to prolonged and cumulative pollution as a result of human activities such as mining, agricultural, industrial and human settlements in their catchments. The objective of this study was to investigate spatial variability of heavy metal pollution of sediments and possible sources of pollutants in two streams of the Olifants River System, South Africa. Stream sediments were collected and analysed for Arsenic (As), Cadmium (Cd), Chromium (Cr), Copper (Cu), Lead (Pb), Nickel (Ni) and Zinc (Zn) concentrations using inductively coupled plasma-mass mass spectrometry (ICP-MS). In both rivers, As, Cd, Cu, Pb and Zn fell within the concentration ranges recommended by CCME and ANZECC, while the concentrations of Cr and Ni exceeded the standards; the results indicated that Cr and Ni in the sediments originated from human activities and not from natural geological background. The index of geo-accumulation (Igeo) was used to assess the degree of pollution. The results of the geo-accumulation index evaluation showed that Cr and Ni were present in the sediments of the rivers at moderately to extremely polluted levels, while As, Cd, Cu, Pb and Zn existed at unpolluted to moderately polluted levels. Generally, heavy metal concentrations increased along the gradient in the rivers. The high concentrations of Cr and Ni in both rivers are of great concern, as previously these two rivers were classified to be supplying the Olifants River with water of good quality. There is a critical need, therefore to monitor heavy metal concentrations and distributions, as well as a comprehensive plan to prevent health risks, especially those communities still reliant on untreated water from the rivers, as sediment pollution may pose a risk of secondary water pollution under sediment disturbance and/or changes in the geo-chemistry of sediments.

Keywords: geo-accumulation index, heavy metals, sediment pollution, water quality

Procedia PDF Downloads 122

Authors: Niki Hayatgheib, SéGolèNe Calvez, Catherine Fournel, Lionel Pineau, Herve Pouliquen, Emmanuelle Moreau

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Furunculosis caused by infection with Aeromonas salmonicida subsp. salmonicida has been a known disease found principally in salmonid aquaculture. Vaccination has been partly successful in preventing this disease, but outbreaks still occur. The application of functional feed additive found to be a promising yield to improve fish health against diseases. In this study, we tested the efficacy of prebiotics and plant essential oils-enriched diet on immune response and disease resistance in vaccinated and non-vaccinated rainbow trout (Oncorhynchus mykiss) against furunculosis. A total of 600 fish were fed with the basal diet or supplement. On 4th week of feeding, fish were vaccinated with an autovaccine. Following 8 weeks, fish were challenged with Aeromonas salmonicida subsp. salmonicida and mortalities were recorded for 3 weeks. Lysozyme activity and antibody titer in serum were measured in different groups. The results of this study showed that lysozyme and circulatory antibody titer in plasma elevated significantly in vaccinated fish fed with additive. The best growth rate and relative percentage survival (62%) were in fish fed with a supplement, while 15% in control fish. Overall, prebiotics and essential oils association can be considered as a potential component for enhancing vaccine efficacy against furunculosis by increasing the growth performance, immune responses and disease resistance in rainbow trout.

Keywords: aeromonas salmonicida subsp. salmonicida, aquaculture, disease resistance, fish, immune response, prebiotics-essential oils feed additive, rainbow trout, vaccination

Procedia PDF Downloads 87

Authors: Mir Md Abdus Salam, Muhammad Mohsin, Pertti Pulkkinen, Paavo Pelkonen, Ari Pappinen

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Soils contaminated with metals, e.g., copper (Cu), zinc (Zn) and nickel (Ni) are one of the main global environmental problems. Zn is an important element for plant growth, but excess levels may become a threat to plant survival. Soils polluted with metals may also pose risks and hazards to human health. Afforestation based on short rotation Salix crops may be a good solution for the reduction of metals toxicity levels in the soil and in ecosystem restoration of severely polluted sites. In a greenhouse experiment, plant growth and zinc (Zn) uptake by four Salix cultivars grown in Zn contaminated soils collected from a mining area in Finland were tested to assess their suitability for phytoextraction. The sequential extraction technique and inductively coupled plasma‒mass spectrometry (ICP–MS) were used to determine the extractable metals and evaluate the fraction of metals in the soil that could be potentially available for plant uptake. The cultivars displayed resistance to heavily polluted soils throughout the whole experiment. After uptake, the total mean Zn concentrations ranged from 776 to 1823 mg kg⁻¹. The average uptake percentage of Zn across all cultivars and treatments ranged from 97 to 223%. Lime and wood ash addition showed a significant effect on plant dry biomass growth and metal uptake percentage of Zn in most of the cultivars. The results revealed that Salix cultivars have the potential to accumulate and take up significant amounts of Zn. Ecological restoration of polluted soils could be environmentally favorable in conjunction with economically profitable practices, such as forestry and bioenergy production. As such, the utilization of Salix for phytoextraction and bioenergy purposes is of considerable interest.

Keywords: lime, phytoextraction, Salix, wood ash, zinc

Procedia PDF Downloads 129

Authors: Sara Arafeh, Kovriguine Evguine

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Cytochromes P450 are enzymes that require a supply of electrons to catalyze the synthesis of steroid hormones, fatty acids, and prostaglandin hormone. Cytochrome P450 Oxidoreductase (CYPOR), a membrane bound enzyme, provides these electrons in its open conformation. CYPOR has two cytosolic domains (FAD domain and FMN domain) and an N-terminal in the membrane. In its open conformation, electrons flow from NADPH, FAD, and finally to FMN where cytochrome P450 picks up these electrons. In the closed conformation, cytochrome P450 does not bind to the FMN domain to take the electrons. It was found that when the cytosolic domains are isolated, CYPOR could not bind to cytochrome P450. This suggested that the membrane environment is important for CYPOR function. This project takes the initiative to better understand the dynamics of CYPOR in its full length. Here, we determine the distance between specific sites in the FAD and FMN binding domains in CYPOR by Forster Resonance Energy Transfer (FRET) and Ultrafast TA spectroscopy with and without NADPH. The approach to determine these distances will rely on labeling these sites with red and infrared fluorophores. Mimic membrane attachment is done by inserting CYPOR in lipid nanodiscs. By determining the distances between the donor-acceptor sites in these domains, we can observe the open/closed conformations upon reducing CYPOR in the presence and absence of cytochrome P450. Such study is important to better understand CYPOR mechanism of action in various endosomal membranes including hepatic CYPOR which is vital in plasma cholesterol homeostasis. By investigating the conformational cycles of CYPOR, we can synthesize drugs that would be more efficient in affecting the steroid hormonal levels and metabolism of toxins catalyzed by Cytochrome P450.

Keywords: conformational cycle of CYPOR, cytochrome P450, cytochrome P450 oxidoreductase, FAD domain, FMN domain, FRET, Ultrafast TA Spectroscopy

Procedia PDF Downloads 245

Authors: Nehal Adel Khalil, Amel Foad Ketat, Fairouz Elsayed Mohamed Ali, Nahla Abdelmoneim Hamid, Hazem Farag Manaa

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Background: Chronic myeloid leukemia (CML) represents 15% of adult leukemias. Imatinib Mesylate (IM) is the gold standard treatment for new cases of CML. Treatment with IM results in improvement of the majority of cases. However, about 25% of cases may develop resistance. Sensitive and specific early predictors of IM resistance in CML patients have not been established to date. Aim: To investigate the value of miR-451 in CML as an early predictor for IM resistance in Egyptian CML patients. Methods: The study employed Real time Polymerase Reaction (qPCR) technique to investigate the leucocytic expression of miR-451 in fifteen newly diagnosed CML patients (group I), fifteen IM responder CML patients (group II), fifteen IM resistant CML patients (group III) and fifteen healthy subjects of matched age and sex as a control group (group IV). The response to IM was defined as < 10% BCR-ABL transcript level after 3 months of therapy. The following parameters were assessed in subjects of all the studied groups: 1- Complete blood count (CBC). 2- Measurement of plasma level of miRNA 451 using real-time Polymerase Chain Reaction (qPCR). 3- Detection of BCR-ABL gene mutation in CML using qPCR. Results: The present study revealed that miR-451 was significantly down-regulated in leucocytes of newly diagnosed CML patients as compared to healthy subjects. IM responder CML patients showed an up-regulation of miR- 451 compared with IM resistant CML patients. Conclusion: According to the data from the present study, it can be concluded that leucocytic miR- 451 expression is a useful additional follow-up marker for the response to IM and a promising prognostic biomarker for CML.

Keywords: chronic myeloid leukemia, imatinib resistance, microRNA 451, Polymerase Chain Reaction

Procedia PDF Downloads 273

Authors: Fang Liu, Jia Jia Yao, Guan Lin Wu, Ren Jie Liu, Zhuang Guo

Abstract:

Leveraging plasma-assisted molecular beam epitaxy (PA-MBE) on c-plane free-standing GaN substrates, this work demonstrates high-performance AlN/GaN double-barrier resonant tunneling diodes (RTDs) featuring stable and repeatable negative differential resistance (NDR) characteristics at room temperature. By scaling down the barrier thickness of AlN and the lateral mesa size of collector, a record peak current density of 1551 kA/cm2 is achieved, accompanied by a peak-to-valley current ratio (PVCR) of 1.24. This can be attributed to the reduced resonant tunneling time under thinner AlN barrier and the suppressed external incoherent valley current by reducing the dislocation number contained in the RTD device with the smaller size of collector. Statistical analysis of the NDR performance of RTD devices with different AlN barrier thicknesses reveals that, as the AlN barrier thickness decreases from 1.5 nm to 1.25 nm, the average peak current density increases from 145.7 kA/cm2 to 1215.1 kA/cm2, while the average PVCR decreases from 1.45 to 1.1, and the peak voltage drops from 6.89 V to 5.49 V. The peak current density obtained in this work represents the highest value reported for nitride-based RTDs to date, while maintaining a high PVCR value simultaneously. This illustrates that an ultra-scaled RTD based on a vertical quantum-well structure and lateral collector size is a valuable approach for the development of nitride-based RTDs with excellent NDR characteristics, revealing their great potential applications in high-frequency oscillation sources and high-speed switch circuits.

Keywords: GaN resonant tunneling diode, peak current density, peak-to-valley current ratio, negative differential resistance

Procedia PDF Downloads 18

Authors: Abdulwahhab Khedr, Tamer Shehata, Hanaa El-Ghamry

Abstract:

Venlafaxine HCl is a novel antidepressant drug used in the treatment of major depressive disorder, generalized anxiety disorder, social anxiety disorder and panic disorder. Conventional therapeutic regimens with venlafaxine HCl immediate-release dosage forms require frequent dosing due to short elimination half-life of the drug and reduced bioavailability. Hence, this study was carried out to develop sustained-release dosage forms of venlafaxine HCl to reduce its dosing frequency, to improve patient compliance and to reduce side effects of the drug. The polymers used were hydroxypropylmethyl cellulose, xanthan gum, sodium alginate, sodium carboxymethyl cellulose, Carbopol 940 and ethyl cellulose. The physical properties of the prepared tablets including tablet thickness, diameter, weight uniformity, content uniformity, hardness and friability were evaluated. Also, the in-vitro release of venlafaxine HCl from different matrix tablets was studied. Based on physical characters and in-vitro release profiles, certain formulae showing promising sustained-release profiles were subjected to film coating with 15% w/v EC in dichloromethane/ethanol mixture (1:1 ratio) using 1% w/v HPMC as pore former and 30% w/w dibutyl phthalate as plasticizer. The optimized formulations were investigated for drug-excipient compatibility using FTIR and DSC studies. Physical evaluation of the prepared tablets fulfilled the pharmacopoeial requirements for tablet friability test, where the weight loss of the prepared formulae did not exceed 1% of the weight of the tested tablets. Moderate release was obtained from tablets containing HPMC. FTIR and DSC studies for such formulae revealed the absence of any type of chemical interaction between venlafaxine HCl and the used polymers or excipients. Forced swimming test in rats was used to evaluate the antidepressant activity of the selected matrix tablets of venlafaxine HCl. Results showed that formulations significantly decreased the duration of animals’ immobility during the 24 hr-period of the test compared to non-treated group.

Keywords: antidepressant, sustained-release, matrix tablet, venlafaxine hydrochloride

Procedia PDF Downloads 202