Search results for: lithium toxicity
379 Efficiency of Wood Vinegar Mixed with Some Plants Extract against the Housefly (Musca domestica L.)
Authors: U. Pangnakorn, S. Kanlaya
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The efficiency of wood vinegar mixed with each individual of three plants extract such as: citronella grass (Cymbopogon nardus), neem seed (Azadirachta indica A. Juss), and yam bean seed (Pachyrhizus erosus Urb.) were tested against the second instar larvae of housefly (Musca domestica L.). Steam distillation was used for extraction of the citronella grass while neem and yam bean were simple extracted by fermentation with ethyl alcohol. Toxicity test was evaluated in laboratory based on two methods of larvicidal bioassay: topical application method (contact poison) and feeding method (stomach poison). Larval mortality was observed daily and larval survivability was recorded until the survived larvae developed to pupae and adults. The study resulted that treatment of wood vinegar mixed with citronella grass showed the highest larval mortality by topical application method (50.0%) and by feeding method (80.0%). However, treatment of mixed wood vinegar and neem seed showed the longest pupal duration to 25 day and 32 days for topical application method and feeding method respectively. Additional, larval duration on treated M. domestica larvae was extended to 13 days for topical application method and 11 days for feeding method. Thus, the feeding method gave higher efficiency compared with the topical application method.Keywords: housefly (Musca domestica L.), neem seed (Azadirachta indica), citronella grass (Cymbopogon nardus), yam bean seed (Pachyrhizus erosus), mortality
Procedia PDF Downloads 337378 Development of Drug Delivery Systems for Endoplasmic Reticulum Amino Peptidases Modulators Using Electrospinning
Authors: Filipa Vasconcelos
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The administration of endoplasmic reticulum amino peptidases (ERAP1 or ERAP2) inhibitors can be used for therapeutic approaches against cancer and auto-immune diseases. However, one of the main shortcomings of drug delivery systems (DDS) is associated with the drug off-target distribution, which can lead to an increase in its side effects on the patient’s body. To overcome such limitations, the encapsulation of four representative compounds of ERAP inhibitors into Polycaprolactone (PCL), Polyvinyl-alcohol (PVA), crosslinked PVA, and PVA with nanoparticles (liposomes) electrospun fibrous meshes is proposed as a safe and controlled drug release system. The use of electrospun fibrous meshes as a DDS allows efficient solvent evaporation giving limited time to the encapsulated drug to recrystallize, continuous delivery of the drug while the fibers degrade, prevention of initial burst release (sustained release), tunable dosages, and the encapsulation of other agents. This is possible due to the fibers' small diameters and resemblance to the extracellular matrix (confirmed by scanning electron microscopy results), high specific surface area, and good mechanical strength/stability. Furthermore, release studies conducted on PCL, PVA, crosslinked PVA, and PVA with nanoparticles (liposomes) electrospun fibrous meshes with each of the ERAP compounds encapsulated demonstrated that they were capable of releasing >60%, 50%, 40%, and 45% of the total ERAP concentration, respectively. Fibrous meshes with ERAP_E compound encapsulated achieved higher released concentrations (75.65%, 62.41%, 56.05%, and 65.39%, respectively). Toxicity studies of fibrous meshes with encapsulated compounds are currently being accessed in vitro, as well as pharmacokinetics and dynamics studies. The last step includes the implantation of the drug-loaded fibrous meshes in vivo.Keywords: drug delivery, electrospinning, ERAP inhibitors, liposomes
Procedia PDF Downloads 95377 Feasibility Study of Mine Tailing’s Treatment by Acidithiobacillus thiooxidans DSM 26636
Authors: M. Gómez-Ramírez, A. Rivas-Castillo, I. Rodríguez-Pozos, R. A. Avalos-Zuñiga, N. G. Rojas-Avelizapa
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Among the diverse types of pollutants produced by anthropogenic activities, metals represent a serious threat, due to their accumulation in ecosystems and their elevated toxicity. The mine tailings of abandoned mines contain high levels of metals such as arsenic (As), zinc (Zn), copper (Cu), and lead (Pb), which do not suffer any degradation process, they are accumulated in environment. Abandoned mine tailings potentially could contaminate rivers and aquifers representing a risk for human health due to their high metal content. In an attempt to remove the metals and thereby mitigate the environmental pollution, an environmentally friendly and economical method of bioremediation has been introduced. Bioleaching has been actively studied over the last several years, and it is one of the bioremediation solutions used to treat heavy metals contained in sewage sludge, sediment and contaminated soil. Acidithiobacillus thiooxidans, an extremely acidophilic, chemolithoautotrophic, gram-negative, rod shaped microorganism, which is typically related to Cu mining operations (bioleaching), has been well studied for industrial applications. The sulfuric acid produced plays a major role in bioleaching. Specifically, Acidithiobacillus thiooxidans strain DSM 26636 has been able to leach Al, Ni, V, Fe, Mg, Si, and Ni contained in slags from coal combustion wastes. The present study reports the ability of A. thiooxidans DSM 26636 for the bioleaching of metals contained in two different mine tailing samples (MT1 and MT2). It was observed that Al, Fe, and Mn were removed in 36.3±1.7, 191.2±1.6, and 4.5±0.2 mg/kg for MT1, and in 74.5±0.3, 208.3±0.5, and 20.9±0.1 for MT2. Besides, < 1.5 mg/kg of Au and Ru were also bioleached from MT1; in MT2, bioleaching of Zn was observed at 55.7±1.3 mg/kg, besides removal of < 1.5 mg/kg was observed for As, Ir, Li, and 0.6 for Os in this residue. These results show the potential of strain DSM 26636 for the bioleaching of metals that came from different mine tailings.Keywords: A. thiooxidans, bioleaching, metals, mine tailings
Procedia PDF Downloads 280376 Transesterification of Waste Cooking Oil for Biodiesel Production Using Modified Clinoptilolite Zeolite as a Heterogeneous Catalyst
Authors: D. Mowla, N. Rasti, P. Keshavarz
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Reduction of fossil fuels sources, increasing of pollution gases emission, and global warming effects increase the demand of renewable fuels. One of the main candidates of alternative fuels is biodiesel. Biodiesel limits greenhouse gas effects due to the closed CO2 cycle. Biodiesel has more biodegradability, lower combustion emissions such as CO, SOx, HC, PM and lower toxicity than petro diesel. However, biodiesel has high production cost due to high price of plant oils as raw material. So, the utilization of waste cooking oils (WCOs) as feedstock, due to their low price and disposal problems reduce biodiesel production cost. In this study, production of biodiesel by transesterification of methanol and WCO using modified sodic potassic (SP) clinoptilolite zeolite and sodic potassic calcic (SPC) clinoptilolite zeolite as heterogeneous catalysts have been investigated. These natural clinoptilolite zeolites were modified by KOH solution to increase the site activity. The optimum biodiesel yields for SP clinoptilolite and SPC clinoptilolite were 95.8% and 94.8%, respectively. Produced biodiesel were analyzed and compared with petro diesel and ASTM limits. The properties of produced biodiesel confirm well with ASTM limits. The density, kinematic viscosity, cetane index, flash point, cloud point, and pour point of produced biodiesel were all higher than petro diesel but its acid value was lower than petro diesel. Finally, the reusability and regeneration of catalysts were investigated. The results indicated that the spent zeolites cannot be reused directly for the transesterification, but they can be regenerated easily and can obtain high activity.Keywords: biodiesel, renewable fuel, transesterification, waste cooking oil
Procedia PDF Downloads 231375 Strategic Metals and Rare Earth Elements Exploration of Lithium Cesium Tantalum Type Pegmatites: A Case Study from Northwest Himalayas
Authors: Auzair Mehmood, Mohammad Arif
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The LCT (Li, Cs and Ta rich)-type pegmatites, genetically related to peraluminous S-type granites, are being mined for strategic metals (SMs) and rare earth elements (REEs) around the world. This study investigates the SMs and REEs potentials of pegmatites that are spatially associated with an S-type granitic suite of the Himalayan sequence, specifically Mansehra Granitic Complex (MGC), northwest Pakistan. Geochemical signatures of the pegmatites and some of their mineral extracts were analyzed using Inductive Coupled Plasma Mass Spectroscopy (ICP-MS) technique to explore and generate potential prospects (if any) for SMs and REEs. In general, the REE patterns of the studied whole-rock pegmatite samples show tetrad effect and possess low total REE abundances, strong positive Europium (Eu) anomalies, weak negative Cesium (Cs) anomalies and relative enrichment in heavy REE. Similar features have been observed on the REE patterns of the feldspar extracts. However, the REE patterns of the muscovite extracts reflect preferential enrichment and possess negative Eu anomalies. The trace element evaluation further suggests that the MGC pegmatites have undergone low levels of fractionation. Various trace elements concentrations (and their ratios) including Ta versus Cs, K/Rb (Potassium/Rubidium) versus Rb and Th/U (Thorium/Uranium) versus K/Cs, were used to analyze the economically viable mineral potential of the studied rocks. On most of the plots, concentrations fall below the dividing line and confer either barren or low-level mineralization potential of the studied rocks for both SMs and REEs. The results demonstrate paucity of the MGC pegmatites with respect to Ta-Nb (Tantalum-Niobium) mineralization, which is in sharp contrast to many Pan-African S-type granites around the world. The MGC pegmatites are classified as muscovite pegmatites based on their K/Rb versus Cs relationship. This classification is consistent with the occurrence of rare accessory minerals like garnet, biotite, tourmaline, and beryl. Furthermore, the classification corroborates with an earlier sorting of the MCG pegmatites into muscovite-bearing, biotite-bearing, and subordinate muscovite-biotite types. These types of pegmatites lack any significant SMs and REEs mineralization potentials. Field relations, such as close spatial association with parent granitic rocks and absence of internal zonation structure, also reflect the barren character and hence lack of any potential prospects of the MGC pegmatites.Keywords: exploration, fractionation, Himalayas, pegmatites, rare earth elements
Procedia PDF Downloads 196374 Preparation of β-Polyvinylidene Fluoride Film for Self-Charging Lithium-Ion Battery
Authors: Nursultan Turdakyn, Alisher Medeubayev, Didar Meiramov, Zhibek Bekezhankyzy, Desmond Adair, Gulnur Kalimuldina
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In recent years the development of sustainable energy sources is getting extensive research interest due to the ever-growing demand for energy. As an alternative energy source to power small electronic devices, ambient energy harvesting from vibration or human body motion is considered a potential candidate. Despite the enormous progress in the field of battery research in terms of safety, lifecycle and energy density in about three decades, it has not reached the level to conveniently power wearable electronic devices such as smartwatches, bands, hearing aids, etc. For this reason, the development of self-charging power units with excellent flexibility and integrated energy harvesting and storage is crucial. Self-powering is a key idea that makes it possible for the system to operate sustainably, which is now getting more acceptance in many fields in the area of sensor networks, the internet of things (IoT) and implantable in-vivo medical devices. For solving this energy harvesting issue, the self-powering nanogenerators (NGS) were proposed and proved their high effectiveness. Usually, sustainable power is delivered through energy harvesting and storage devices by connecting them to the power management circuit; as for energy storage, the Li-ion battery (LIB) is one of the most effective technologies. Through the movement of Li ions under the driving of an externally applied voltage source, the electrochemical reactions generate the anode and cathode, storing the electrical energy as the chemical energy. In this paper, we present a simultaneous process of converting the mechanical energy into chemical energy in a way that NG and LIB are combined as an all-in-one power system. The electrospinning method was used as an initial step for the development of such a system with a β-PVDF separator. The obtained film showed promising voltage output at different stress frequencies. X-ray diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FT-IR) analysis showed a high percentage of β phase of PVDF polymer material. Moreover, it was found that the addition of 1 wt.% of BTO (Barium Titanate) results in higher quality fibers. When comparing pure PVDF solution with 20 wt.% content and the one with BTO added the latter was more viscous. Hence, the sample was electrospun uniformly without any beads. Lastly, to test the sensor application of such film, a particular testing device has been developed. With this device, the force of a finger tap can be applied at different frequencies so that electrical signal generation is validated.Keywords: electrospinning, nanogenerators, piezoelectric PVDF, self-charging li-ion batteries
Procedia PDF Downloads 158373 Effect of Different Arsenic Treatments on Root Growth of Sunflower Seedlings in Rhizobox Experiment
Authors: Szilvia Várallyay, Béla Kovács, Éva Bódi, Farzeneh Garousi, Szilvia Veres
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Arsenic (As) is a naturally occurring substance that can be present in soil, water and air. Vegetables, fruits, and other plants that grow in contaminated soils which are able to accumulate arsenic. Arsenic when presents in plant cells, has various negative physiological effects and when presents in soil will be inorgaic form, namely arsenite (As(III)) and arsenate (As(V)). These two forms of arsenic disrupt plant metabolism by inhibiting its growth and these arsenic species has negative effect on nutrient uptake. A rhizobox experiment was conducted to investigate the effect of arsenite and arsenate on root growth of sunflower seedlings. Sunflower plants were grown in climatic room under irradiance of 300 µmol m-2 s-1, 16-h day and 8-h night photoperiod, day/night temperature of 25/20°C and relative humidity of 65-75%. We applied arsenic in form of arsenite (NaAsO2) and arsenate (KH2AsO4), respectively. The applied arsenic treatments was 0, 10, 30, 90 mg.kg-1. After disinfection, seeds were germinated between moist filter papers. Seedlings with 2-3 cm coleoptils were placed into rhizoboxes. In the rhizoboxes the growing and daily growing rhythm of roots of sunflower can be followed up, moreover possible phytotoxic symptoms of roots resulting from increasing arsenic can be seen. Weights of rhizoboxes were measured daily and also evaporated water added each day. The lengths of roots were measured daily until seedlings roots get at the end of the rhizoboxes. Negative correlation was observed between the higher concentration of arsenic in the soil and the growth of sunflower seedlings roots. The effect of arsenic toxicity was more considerable in 90 mg.kg-1 arsenic treatment than lower concentration. The same arsenite concentration causes slower growth in case of sunflower plant than the same arsenate concentration produced.Keywords: arsenic, rhizobox experiment, sunflower, root growth
Procedia PDF Downloads 411372 Application and Limitation of Heavy Metal Pollution Indicators in Coastal Environment of Pakistan
Authors: Noor Us Saher
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Oceans and Marine areas have a great importance, mainly regarding food resources, fishery products and reliance of livelihood. Aquatic pollution is common due to the incorporation of various chemicals mainly entering from urbanization, industrial and commercial facilities, such as oil and chemical spills. Many hazardous wastes and industrial effluents contaminate the nearby areas and initiate to affect the marine environment. These contaminated conditions may become worse in those aquatic environments situated besides the world’s largest cities, which are hubs of various commercial activities. Heavy metal contamination is one of the most important predicaments for marine environments and during past decades this problem has intensified due to an increase in urbanization and industrialization. Coastal regions of Pakistan are facing severe threats from various organic and inorganic pollutants, especially the estuarine and coastal areas of Karachi city, the most populated and industrialized city situated along the coastline. Metal contamination causes severe toxicity in biota resulting the degradation of Marine environments and depletion of fishery resources and sustainability. There are several abiotic (air, water and sediment) and biotic (fauna and flora) indicators that indicate metal contamination. However, all these indicators have certain limitations and complexities, which delay their implementation for rehabilitation and conservation in the marine environment. The inadequate evidences have presented on this significant topic till the time and this study discussed metal pollution and its consequences along the marine environment of Pakistan. This study further helps in identification of possible hazards for the ecological system and allied resources for management strategies and decision making for sustainable approaches.Keywords: coastal and estuarine environment, heavy metals pollution, pollution indicators, Pakistan
Procedia PDF Downloads 244371 Achieving Net Zero Energy Building in a Hot Climate Using Integrated Photovoltaic and Parabolic Trough Collectors
Authors: Adel A. Ghoneim
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In most existing buildings in hot climate, cooling loads lead to high primary energy consumption and consequently high CO2 emissions. These can be substantially decreased with integrated renewable energy systems. Kuwait is characterized by its dry hot long summer and short warm winter. Kuwait receives annual total radiation more than 5280 MJ/m2 with approximately 3347 h of sunshine. Solar energy systems consist of PV modules and parabolic trough collectors are considered to satisfy electricity consumption, domestic water heating, and cooling loads of an existing building. This paper presents the results of an extensive program of energy conservation and energy generation using integrated photovoltaic (PV) modules and parabolic trough collectors (PTC). The program conducted on an existing institutional building intending to convert it into a Net-Zero Energy Building (NZEB) or near net Zero Energy Building (nNZEB). The program consists of two phases; the first phase is concerned with energy auditing and energy conservation measures at minimum cost and the second phase considers the installation of photovoltaic modules and parabolic trough collectors. The 2-storey building under consideration is the Applied Sciences Department at the College of Technological Studies, Kuwait. Single effect lithium bromide water absorption chillers are implemented to provide air conditioning load to the building. A numerical model is developed to evaluate the performance of parabolic trough collectors in Kuwait climate. Transient simulation program (TRNSYS) is adapted to simulate the performance of different solar system components. In addition, a numerical model is developed to assess the environmental impacts of building integrated renewable energy systems. Results indicate that efficient energy conservation can play an important role in converting the existing buildings into NZEBs as it saves a significant portion of annual energy consumption of the building. The first phase results in an energy conservation of about 28% of the building consumption. In the second phase, the integrated PV completely covers the lighting and equipment loads of the building. On the other hand, parabolic trough collectors of optimum area of 765 m2 can satisfy a significant portion of the cooling load, i.e about73% of the total building cooling load. The annual avoided CO2 emission is evaluated at the optimum conditions to assess the environmental impacts of renewable energy systems. The total annual avoided CO2 emission is about 680 metric ton/year which confirms the environmental impacts of these systems in Kuwait.Keywords: building integrated renewable systems, Net-Zero energy building, solar fraction, avoided CO2 emission
Procedia PDF Downloads 600370 Photoelectrochemical Water Splitting from Earth-Abundant CuO Thin Film Photocathode: Enhancing Performance and Photo-Stability through Deposition of Overlayers
Authors: Wilman Septina, Rajiv R. Prabhakar, Thomas Moehl, David Tilley
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Cupric oxide (CuO) is a promising absorber material for the fabrication of scalable, low cost solar energy conversion devices, due to the high abundance and low toxicity of copper. It is a p-type semiconductor with a band gap of around 1.5 eV, absorbing a significant portion of the solar spectrum. One of the main challenges in using CuO as solar absorber in an aqueous system is its tendency towards photocorrosion, generating Cu2O and metallic Cu. Although there have been several reports of CuO as a photocathode for hydrogen production, it is unclear how much of the observed current actually corresponds to H2 evolution, as the inevitability of photocorrosion is usually not addressed. In this research, we investigated the effect of the deposition of overlayers onto CuO thin films for the purpose of enhancing its photostability as well as performance for water splitting applications. CuO thin film was fabricated by galvanic electrodeposition of metallic copper onto gold-coated FTO substrates, followed by annealing in air at 600 °C. Photoelectrochemical measurement of the bare CuO film using 1 M phosphate buffer (pH 6.9) under simulated AM 1.5 sunlight showed a current density of ca. 1.5 mA cm-2 (at 0.4 VRHE), which photocorroded to Cu metal upon prolonged illumination. This photocorrosion could be suppressed by deposition of 50 nm-thick TiO2, deposited by atomic layer deposition. In addition, we found that insertion of an n-type CdS layer, deposited by chemical bath deposition, between the CuO and TiO2 layers was able to enhance significantly the photocurrent compared to without the CdS layer. A photocurrent of over 2 mA cm-2 (at 0 VRHE) was observed using the photocathode stack FTO/Au/CuO/CdS/TiO2/Pt. Structural, electrochemical, and photostability characterizations of the photocathode as well as results on various overlayers will be presented.Keywords: CuO, hydrogen, photoelectrochemical, photostability, water splitting
Procedia PDF Downloads 212369 Policy Initiatives That Increase Mass-Market Participation of Fuel Cell Electric Vehicles
Authors: Usman Asif, Klaus Schmidt
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In recent years, the development of alternate fuel vehicles has helped to reduce carbon emissions worldwide. As the number of vehicles will continue to increase in the future, the energy demand will also increase. Therefore, we must consider automotive technologies that are efficient and less harmful to the environment in the long run. Battery Electric Vehicles (BEVs) have gained popularity in recent years because of their lower maintenance, lower fuel costs, and lower carbon emissions. Nevertheless, BEVs show several disadvantages, such as slow charging times and lower range than traditional combustion-powered vehicles. These factors keep many people from switching to BEVs. The authors of this research believe that these limitations can be overcome by using fuel cell technology. Fuel cell technology converts chemical energy into electrical energy from hydrogen power and therefore serves as fuel to power the motor and thus replacing heavy lithium batteries that are expensive and hard to recycle. Also, in contrast to battery-powered electric vehicle technology, Fuel Cell Electric Vehicles (FCEVs) offer higher ranges and lower fuel-up times and therefore are more competitive with electric vehicles. However, FCEVs have not gained the same popularity as electric vehicles due to stringent legal frameworks, underdeveloped infrastructure, high fuel transport, and storage costs plus the expense of fuel cell technology itself. This research will focus on the legal frameworks for hydrogen-powered vehicles, and how a change in these policies may affect and improve hydrogen fueling infrastructure and lower hydrogen transport and storage costs. These policies may also facilitate reductions in fuel cell technology costs. In order to attain a better framework, a number of countries have developed conceptual roadmaps. These roadmaps have set out a series of objectives to increase the access of FCEVs to their respective markets. This research will specifically focus on policies in Japan, Europe, and the USA in their attempt to shape the automotive industry of the future. The researchers also suggest additional policies that may help to accelerate the advancement of FCEVs to mass-markets. The approach was to provide a solid literature review using resources from around the globe. After a subsequent analysis and synthesis of this review, the authors concluded that in spite of existing legal challenges that have hindered the advancement of fuel-cell technology in the automobile industry in the past, new initiatives that enhance and advance the very same technology in the future are underway.Keywords: fuel cell electric vehicles, fuel cell technology, legal frameworks, policies and regulations
Procedia PDF Downloads 107368 Ecological and Biological Effects of Pollution and Dredging Activities on Fisheries and Fisheries Products in Niger Delta Ecological Zone
Authors: Ikpesu, Thomas Ohwofasa, Babtunde Ilesanmi
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The effects of anthropogenic activities on fish and fisheries products in Niger Delta water bodies were investigated. The rivers were selected based on their close proximity to contaminants and dredging activities. Three stations were chosen per river. The stations chosen to depicting downstream and upstream stations were visited and samples collected on monthly basis. The down streams stations are the polluted and heavily dredged sites, where the upstream station is far, without any evidence of pollution or human activities. During these periods, the fishes of the same species were collected and analyzed for morphological and physiological changes, after which they were returned back to the rivers. The physico-chemicals parameters of these stations were also taken. Morphological changes such as skin ulcerations and other lesions, as well as fungi infections were observed in the down streams fishes. The fish in up streams look healthier and bigger (though the age could not be affirmed) than the downstream fishes. The physico-chemical parameters between the up streams and down streams stations vary significantly (p < 0.01). These anthropogenic effects must have interfere with the normal migration pattern of these fishes, because there were changes in the composition of population and species diversity in the samples sites, with the upstream having true species diversity. The release of pollutants into the water in the Niger Delta areas may triggers off naturally occurring bio toxicity cycles and other fish poisoning. There is risk of biomagnifications of these poisons along the tropic level. This makes the normally valuable food resource dangerous for human consumption and thereby instances of human death caused by such poisoning.Keywords: anthropogenic, dredging, fisheries, niger delta, pollution, rivers
Procedia PDF Downloads 302367 Lipid-Chitosan Hybrid Nanoparticles for Controlled Delivery of Cisplatin
Authors: Muhammad Muzamil Khan, Asadullah Madni, Nina Filipczek, Jiayi Pan, Nayab Tahir, Hassan Shah, Vladimir Torchilin
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Lipid-polymer hybrid nanoparticles (LPHNP) are delivery systems for controlled drug delivery at tumor sites. The superior biocompatible properties of lipid and structural advantages of polymer can be obtained via this system for controlled drug delivery. In the present study, cisplatin-loaded lipid-chitosan hybrid nanoparticles were formulated by the single step ionic gelation method based on ionic interaction of positively charged chitosan and negatively charged lipid. Formulations with various chitosan to lipid ratio were investigated to obtain the optimal particle size, encapsulation efficiency, and controlled release pattern. Transmission electron microscope and dynamic light scattering analysis demonstrated a size range of 181-245 nm and a zeta potential range of 20-30 mV. Compatibility among the components and the stability of formulation were demonstrated with FTIR analysis and thermal studies, respectively. The therapeutic efficacy and cellular interaction of cisplatin-loaded LPHNP were investigated using in vitro cell-based assays in A2780/ADR ovarian carcinoma cell line. Additionally, the cisplatin loaded LPHNP exhibited a low toxicity profile in rats. The in-vivo pharmacokinetics study also proved a controlled delivery of cisplatin with enhanced mean residual time and half-life. Our studies suggested that the cisplatin-loaded LPHNP being a promising platform for controlled delivery of cisplatin in cancer therapy.Keywords: cisplatin, lipid-polymer hybrid nanoparticle, chitosan, in vitro cell line study
Procedia PDF Downloads 124366 Polymerization of Epsilon-Caprolactone Using Lipase Enzyme for Medical Applications
Authors: Sukanya Devi Ramachandran, Vaishnavi Muralidharan, Kavya Chandrasekaran
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Polycaprolactone is polymer belonging to the polyester family that has noticeable characteristics of biodegradability and biocompatibility which is essential for medical applications. Polycaprolactone is produced by the ring opening polymerization of the monomer epsilon-Caprolactone (ε-CL) which is a closed ester, comprising of seven-membered ring. This process is normally catalysed by metallic components such as stannous octoate. It is difficult to remove the catalysts after the reaction, and they are also toxic to the human body. An alternate route of using enzymes as catalysts is being employed to reduce the toxicity. Lipase enzyme is a subclass of esterase that can easily attack the ester bonds of ε-CL. This research paper throws light on the extraction of lipase from germinating sunflower seeds and the activity of the biocatalyst in the polymerization of ε-CL. Germinating Sunflower seeds were crushed with fine sand in phosphate buffer of pH 6.5 into a fine paste which was centrifuged at 5000rpm for 10 minutes. The clear solution of the enzyme was tested for activity at various pH ranging from 5 to 7 and temperature ranging from 40oC to 70oC. The enzyme was active at pH6.0 and at 600C temperature. Polymerization of ε-CL was done using toluene as solvent with the catalysis of lipase enzyme, after which chloroform was added to terminate the reaction and was washed in cold methanol to obtain the polymer. The polymerization was done by varying the time from 72 hours to 6 days and tested for the molecular weight and the conversion of the monomer. The molecular weight obtained at 6 days is comparably higher. This method will be very effective, economical and eco-friendly to produce as the enzyme used can be regenerated as such at the end of the reaction and can be reused. The obtained polymers can be used for drug delivery and other medical applications.Keywords: lipase, monomer, polycaprolactone, polymerization
Procedia PDF Downloads 291365 Human Metabolism of the Drug Candidate PBTZ169
Authors: Vadim Makarov, Stewart T.Cole
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PBTZ169 is novel drug candidate with high efficacy in animals models, and its combination treatment of PBTZ169 with BDQ and pyrazinamide was shown to be more efficacious than the standard treatment for tuberculosis in a mouse model. The target of PBTZ169 is famous DprE1, an essential enzyme in cell wall biosynthesis. The crystal structure of the DprE1-PBTZ169 complex reveals formation of a semimercaptal adduct with Cys387 in the active site and explains the irreversible inactivation of the enzyme. Furthermore, this drug candidate demonstrated during preclinical research ‘drug like’ properties what made it an attractive drug candidate to treat tuberculosis in humans. During first clinical trials several cohorts of the healthy volunteers were treated by the single doses of PBTZ169 as well as two weeks repeated treatment was chosen for two maximal doses. As expected PBTZ169 was well tolerated, and no significant toxicity effects were observed during the trials. The study of the metabolism shown that human metabolism of PBTZ169 is very different from microbial or animals compound transformation. So main pathway of microbial, mice and less rats metabolism connected with reduction processes, but human metabolism mainly connected with oxidation processes. Due to this difference we observed several metabolites of PBTZ169 in humans with antitubercular activity, and now we can conclude that animal antituberculosis activity of PBTZ169 is a result not only activity of the drug itself, but it is a result of the sum activity of the drug and its metabolites. Direct antimicrobial plasma activity was studied, and such activity was observed for 24 hours after human treatment for some doses. This data gets high chance for good efficacy of PBTZ169 in human for treatment TB infection. Second phase of clinical trials was started summer of 2017 and continues to the present day. Available data will be presented.Keywords: clinical trials, DprE1, PBTZ169, metabolism
Procedia PDF Downloads 158364 Hepatic Regenerative Capacity after Acetaminophen-Induced Liver Injury in Mouse Model
Authors: N. F. Hamid, A. Kipar, J. Stewart, D. J. Antoine, B. K. Park, D. P. Williams
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Acetaminophen (APAP) is a widely used analgesic that is safe at therapeutic doses. The mouse model of APAP has been extensively used for studies on pathogenesis and intervention of drug induced liver injury based on the CytP450 mediated formation of N-acetyl-p-benzo-quinoneimine and, more recently, as model for mechanism based biomarkers. Delay of the fasted CD1 mice to rebound to the basal level of hepatic GSH compare to fed mice is reported in this study. Histologically, 15 hours fasted mice prior to APAP treatment leading to overall more intense cell loss with no evidence of apoptosis as compared to non-fasted mice, where the apoptotic cells were clearly seen on cleaved caspase-3 immunostaining. After 15 hours post APAP administration, hepatocytes underwent stage of recovery with evidence of mitotic figures in fed mice and return to completely no histological difference to control at 24 hours. On the contrary, the evidence of ongoing cells damage and inflammatory cells infiltration are still present on fasted mice until the end of the study. To further measure the regenerative capacity of the hepatocytes, the inflammatory mediators of cytokines that involved in the progression or regression of the toxicity like TNF-α and IL-6 in liver and spleen using RT-qPCR were also included. Yet, quantification of proliferating cell nuclear antigen (PCNA) has demonstrated the time for hepatic regenerative in fasted is longer than that to fed mice. Together, these data would probably confirm that fasting prior to APAP treatment does not only modulate liver injury, but could have further effects to delay subsequent regeneration of the hepatocytes.Keywords: acetaminophen, liver, proliferating cell nuclear antigen, regeneration, apoptosis
Procedia PDF Downloads 422363 Preparation and Characterization of Chitosan Nanoparticles for Delivery of Oligonucleotides
Authors: Gyati Shilakari Asthana, Abhay Asthana, Dharm Veer Kohli, Suresh Prasad Vyas
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Purpose: The therapeutic potential of oligonucleotide (ODN) is primarily dependent upon its safe and efficient delivery to specific cells overcoming degradation and maximizing cellular uptake in vivo. The present study is focused to design low molecular weight chitosan nanoconstructs to meet the requirements of safe and effectual delivery of ODNs. LMW-chitosan is a biodegradable, water soluble, biocompatible polymer and is useful as a non-viral vector for gene delivery due to its better stability in water. Methods: LMW chitosan ODN nanoparticles (CHODN NPs) were formulated by self-assembled method using various N/P ratios (moles ratio of amine groups of CH to phosphate moieties of ODNs; 0.5:1, 1:1, 3:1, 5:1, and 7:1) of CH to ODN. The developed CHODN NPs were evaluated with respect to gel retardation assay, particle size, zeta potential and cytotoxicity and transfection efficiency. Results: Complete complexation of CH/ODN was achieved at the charge ratio of 0.5:1 or above and CHODN NPs displayed resistance against DNase I. On increasing the N/P ratio of CH/ODN, the particle size of the NPs decreased whereas zeta potential (ZV) value increased. No significant toxicity was observed at all CH concentrations. The transfection efficiency was increased on increasing N/P ratio from 1:1 to 3:1, whereas it was decreased with further increment in N/P ratio upto 7:1. Maximum transfection of CHODN NPs with both the cell lines (Raw 267.4 cells and Hela cells) was achieved at N/P ratio of 3:1. The results suggest that transfection efficiency of CHODN NPs is dependent on N/P ratio. Conclusion: Thus the present study states that LMW chitosan nanoparticulate carriers would be acceptable choice to improve transfection efficiency in vitro as well as in vivo delivery of oligonucleotide.Keywords: LMW-chitosan, chitosan nanoparticles, biocompatibility, cytotoxicity study, transfection efficiency, oligonucleotide
Procedia PDF Downloads 846362 Late Presentation of Pseudophakic Macula Edema from Oral Kinase Inhibitors: A Case and Literature Review
Authors: Christolyn Raj, Lewis Levitz
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Introduction: Two cases of late presentation ( > five years ) of bilateral pseudophakic macula edema related to oral tyrosine kinase inhibitors are described. These cases are the first of their type in the published literature. A review of ocular inflammatory complications of tyrosine kinase inhibitors in the current literature is explored. Case Presentations(s): Case 1 is an 83-year-old female who has been stable on Ibrutinib (Imbruvica ®) for chronic lymphocytic leukemia (CLL). She presented with bilateral blurred vision from severe cystoid macula edema seven years following routine cataract surgery. She was treated with intravitreal steroids with complete resolution without relapse. Case 2 is a 76-year-old female who was on therapy for polycythemia vera with Ruxolitinib (Jakafi®). She presented with bilateral blurred vision from mild cystoid macula edema six years following routine cataract surgery. She responded well to topical steroids without relapse. In both cases, oral tyrosine kinase inhibitor agents were presumed to be the underlying cause and were ceased. Over the last five years, there have been increasing reports in the literature of the inflammatory effects of tyrosine kinase inhibitors on the retina, uvea and optic nerve. Conclusion: Late presentation of pseudophakic macula edema following routine cataract surgery is rare. Such presentations should prompt investigation of the chronic use of systemic medications, especially oral kinase inhibitors. Patients who must remain on these agents require ongoing ophthalmologic assessment in view of their long-term inflammatory side effects.Keywords: macula edema, oral kinase inhibitors, retinal toxicity, pseudo-phakia
Procedia PDF Downloads 88361 Assessment of Microorganisms in Irrigation Water Collected from Various Vegetable Growing Areas of SWAT Valley, Khyber Pakhtunkhwa
Authors: Islam Zeb
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Water of poor quality has a potential of probable contamination and a way to spread pollutant in the field and surrounding environment. A number of comprehensive reviews articles have been published which highlight irrigation water as a source of pathogenic microorganisms and heavy metals toxicity that leads to chronic diseases in human. Here a study was plan to determine the microbial status of irrigation water collected from various location of district Swat in various months. The analyses were carried out at Environmental Horticulture Laboratory, Department of Horticulture, The University of Agriculture Peshawar, during the year 2018 – 19. The experiment was laid out in Randomized Complete Block Design (RCBD) with two factors and three replicates. Factor A consist of different locations, and factor B represent various months. The results of microbial status for various locations in irrigation water showed the highest value for Total Bacterial Count, Enterobacteriacea, E. coli, Salmonella, and Listeria (9.05, 8.54, 6.01, 5.84, and 5.03 log cfu L-1 respectively) for samples collected from mingora location, whereas the lowest values for Total Bacterial Count, Enterobacteriacea, E. coli, Salmonella and Listeria (6.70, 6.38, 4.47, 4.42 and 3.77 log cfu L-1 respectively) were observed for matta location. Data for various months showed maximum Total Bacterial Count, Enterobacteriacea, E. coli, Salmonella, and Listeria (12.01, 11.70, 8.46, 8.41, and 6.88 log cfu L-1, respectively) were noted for the irrigation water samples collected in May/June whereas the lowest range for Total Bacterial Count, Enterobacteriacea, E. coli, Salmonella and Listeria (4.41, 4.08, 2.61, 2.55 and 3.39 log cfu L-1 respectively) were observed in Jan/Feb. A significant interaction was found for all the studied parameters it was concluded that maximum bacterial groups were recorded in the months of May/June from Mingora location, it might be due to favorable weather condition.Keywords: contamination, irrigation water, microbes, SWAT, various months
Procedia PDF Downloads 61360 Material Use and Life Cycle GHG Emissions of Different Electrification Options for Long-Haul Trucks
Authors: Nafisa Mahbub, Hajo Ribberink
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Electrification of long-haul trucks has been in discussion as a potential strategy to decarbonization. These trucks will require large batteries because of their weight and long daily driving distances. Around 245 million battery electric vehicles are predicted to be on the road by the year 2035. This huge increase in the number of electric vehicles (EVs) will require intensive mining operations for metals and other materials to manufacture millions of batteries for the EVs. These operations will add significant environmental burdens and there is a significant risk that the mining sector will not be able to meet the demand for battery materials, leading to higher prices. Since the battery is the most expensive component in the EVs, technologies that can enable electrification with smaller batteries sizes have substantial potential to reduce the material usage and associated environmental and cost burdens. One of these technologies is an ‘electrified road’ (eroad), where vehicles receive power while they are driving, for instance through an overhead catenary (OC) wire (like trolleybuses and electric trains), through wireless (inductive) chargers embedded in the road, or by connecting to an electrified rail in or on the road surface. This study assessed the total material use and associated life cycle GHG emissions of two types of eroads (overhead catenary and in-road wireless charging) for long-haul trucks in Canada and compared them to electrification using stationary plug-in fast charging. As different electrification technologies require different amounts of materials for charging infrastructure and for the truck batteries, the study included the contributions of both for the total material use. The study developed a bottom-up approach model comparing the three different charging scenarios – plug in fast chargers, overhead catenary and in-road wireless charging. The investigated materials for charging technology and batteries were copper (Cu), steel (Fe), aluminium (Al), and lithium (Li). For the plug-in fast charging technology, different charging scenarios ranging from overnight charging (350 kW) to megawatt (MW) charging (2 MW) were investigated. A 500 km of highway (1 lane of in-road charging per direction) was considered to estimate the material use for the overhead catenary and inductive charging technologies. The study considered trucks needing an 800 kWh battery under the plug-in charger scenario but only a 200 kWh battery for the OC and inductive charging scenarios. Results showed that overall the inductive charging scenario has the lowest material use followed by OC and plug-in charger scenarios respectively. The materials use for the OC and plug-in charger scenarios were 50-70% higher than for the inductive charging scenarios for the overall system including the charging infrastructure and battery. The life cycle GHG emissions from the construction and installation of the charging technology material were also investigated.Keywords: charging technology, eroad, GHG emissions, material use, overhead catenary, plug in charger
Procedia PDF Downloads 49359 EDTA Enhanced Plant Growth, Antioxidant Defense System, and Phytoextraction of Copper by Brassica napus L.
Authors: Ume Habiba, Shafaqat Ali, Mujahid Farid, Muhammad Bilal Shakoor
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Copper (Cu) is an essential micronutrient for normal plant growth and development, but in excess, it is also toxic to plants. The present study investigated the influence of ethylenediaminetetraacetic acid (EDTA) in enhancing Cu uptake and tolerance as well as the morphological and physiological responses of Brassica napus L. seedlings under Cu stress. Four-week-old seedlings were transferred to hydroponics containing Hoagland’s nutrient solution. After 2 weeks of transplanting, three levels (0, 50, and 100 μM) of Cu were applied with or without application of 2.5 mM EDTA and plants were further grown for 8 weeks in culture media. Results showed that Cu alone significantly decreased plant growth, biomass, photosynthetic pigments, and gas exchange characteristics. Cu stress also reduced the activities of antioxidants, such as superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX), and catalase (CAT) along with protein contents. Cu toxicity increased the concentration of reactive oxygen species (ROS) as indicated by the increased production of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in both leaves and roots. The application of EDTA significantly alleviated Cu-induced toxic effects in B. napus, showing remarkable improvement in all these parameters. EDTA amendment increased the activity of antioxidant enzymes by decreasing the concentrations of MDA and H2O2 both in leaves and roots of B. napus. Although, EDTA amendment with Cu significantly increased Cu uptake in roots, stems, and leaves in decreasing order of concentration but increased the growth, photosynthetic parameters, and antioxidant enzymes. These results showed that the application of EDTA can be a useful strategy for phytoextraction of Cu by B. napus from contaminated soils.Keywords: antioxidants, biomass, copper, EDTA, phytoextraction, tolerance
Procedia PDF Downloads 409358 Non-Linear Transformation of Bulk Acoustic Waves at Oblique Incidence on Plane Solid Boundary
Authors: Aleksandr I. Korobov, Natalia V. Shirgina, Aleksey I. Kokshaiskiy
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The transformation of two types of acoustic waves can occur on a flat interface between two solids at oblique incidence of longitudinal and shear bulk acoustic waves (BAW). This paper presents the results of experimental studies of the properties of reflection and propagation of longitudinal wave and generation of second and third longitudinal and shear harmonics of BAW at oblique incidence of longitudinal BAW on a flat rough boundary between two solids. The experimental sample was a rectangular isosceles pyramid made of D16 aluminum alloy with the plane parallel bases cylinder made of D16 aluminum alloy pressed to the base. The piezoelectric lithium niobate transducer with a resonance frequency of 5 MHz was secured to one face of the pyramid to generate a longitudinal wave. Longitudinal waves emitted by this transducer felt at an angle of 45° to the interface between two solids and reflected at the same angle. On the opposite face of the pyramid, and on the flat side of the cylinder was attached longitudinal transducer with resonance frequency of 10 MHz or the shear transducer with resonance frequency of 15 MHz. These transducers also effectively received signal at a frequency of 5 MHz. In the spectrum of the transmitted and reflected BAW was observed shear and longitudinal waves at a frequency of 5 MHz, as well as longitudinal harmonic at a frequency harmonic of 10 MHz and a shear harmonic at frequency of 15 MHz. The effect of reversing changing of external pressure applied to the rough interface between two solids on the value of the first and higher harmonics of the BAW at oblique incidence on the interface of the longitudinal BAW was experimentally investigated. In the spectrum of the reflected signal from the interface, there was a decrease of amplitudes of the first harmonics of the signal, and non-monotonic dependence of the second and third harmonics of shear wave with an increase of the static pressure applied to the interface. In the spectrum of the transmitted signal growth of the first longitudinal and shear harmonic amplitude and non-monotonic dependence - first increase and then decrease in the amplitude of the second and third longitudinal shear harmonic with increasing external static pressure was observed. These dependencies were hysteresis at reversing changing of external pressure. When pressure applied to the border increased, acoustic contact between the surfaces improves. This increases the energy of the transmitted elastic wave and decreases the energy of the reflected wave. The second longitudinal acoustic harmonics generation was associated with the Hertz nonlinearity on the interface of two pressed rough surfaces, the generation of the third harmonic was caused by shear hysteresis nonlinearity due to dry friction on a rough interface. This study was supported by the Russian Science Foundation (project №14-22-00042).Keywords: generation of acoustic harmonics, hysteresis nonlinearity, Hertz nonlinearity, transformation of acoustic waves
Procedia PDF Downloads 375357 Biological Studies of N-O Donor 4-Acypyrazolone Heterocycle and Its Pd/Pt Complexes of Therapeutic Importance
Authors: Omoruyi Gold Idemudia, Alexander P. Sadimenko
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The synthesis of N-heterocycles with novel properties, having broad spectrum biological activities that may become alternative medicinal drugs, have been attracting a lot of research attention due to the emergence of medicinal drug’s limitations such as disease resistance and their toxicity effects among others. Acylpyrazolones have been employed as pharmaceuticals as well as analytical reagent and their application as coordination complexes with transition metal ions have been well established. By way of a condensation reaction with amines acylpyrazolone ketones form a more chelating and superior group of compounds known as azomethines. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one was reacted with phenylhydrazine to get a new phenylhydrazone which was further reacted with aqueous solutions of palladium and platinum salts, in an effort towards the discovery of transition metal based synthetic drugs. The compounds were characterized by means of analytical, spectroscopic, thermogravimetric analysis TGA, as well as x-ray crystallography. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one phenylhydrazone crystallizes in a triclinic crystal system with a P-1 (No. 2) space group based on x-ray crystallography. The bidentate ON ligand formed a square planar geometry on coordinating with metal ions based on FTIR, electronic and NMR spectra as well as magnetic moments. Reported compounds showed antibacterial activities against the nominated bacterial isolates using the disc diffusion technique at 20 mg/ml in triplicates. The metal complexes exhibited a better antibacterial activity with platinum complex having an MIC value of 0.63 mg/ml. Similarly, ligand and complexes also showed antioxidant scavenging properties against 2, 2-diphenyl-1-picrylhydrazyl DPPH radical at 0.5mg/ml relative to ascorbic acid (standard drug).Keywords: acylpyrazolone, antibacterial studies, metal complexes, phenylhydrazone, spectroscopy
Procedia PDF Downloads 247356 Adsorption of Dyes and Iodine: Reaching Outstanding Kinetics with CuII-Based Metal–Organic Nanoballs
Authors: Eder Amayuelas, Begoña Bazán, M. Karmele Urtiaga, Gotzone Barandika, María I. Arriortua
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Metal Organic Frameworks (MOFs) have attracted great interest in recent years, taking a lead role in the field of catalysis, drug delivery, sensors and absorption. In the past decade, promising results have been reported specifically in the field of adsorption, based on the topology and chemical features of this type of porous material. Thus, its application in industry and environment for the adsorption of pollutants is presented as a response to an increasingly important need. In this area, organic dyes are nowadays widely used in many industries including medicine, textile, leather, printing and plastics. The consequence of this fact is that dyes are present as emerging pollutants in soils and water where they remain for long periods of time due to their high stability, with a potential risk of toxicity in wildlife and in humans. On the other hand, the presence of iodine in soils, water and gas as a nuclear activity pollutant product or its extended use as a germicide is still a problem in many countries, which indicates the imperative need for its removal. In this context, this work presents the characterization as an adsorbent of the activated compound αMOP@Ei2-1 obtained from the already reported [Cu₂₄(m-BDC)₂₄(DMF)₂₀(H₂O)₄]•24DMF•40H₂O (MOP@Ei2-1), where m-BDC is the 1,3-benzenedicarboxylic ligand and DMF is N,N′-dimethylformamide. The structure of MOP@Ei2-1 consists of Cu24 clusters arranged in such a way that 12 paddle-wheels are connected through m-BDC ligands. The clusters exhibit an internal cavity where crystallization molecules of DMF and water are located. Adsorption of dyes and iodine as pollutant examples has been carried out, focusing attention on the kinetics of the rapid process.Keywords: adsorption, organic dyes, iodine, metal organic frameworks
Procedia PDF Downloads 266355 Promotive Role of 5-Aminolevulinic Acid on Chromium-Induced Morphological, Photosynthetic and Oxidative Changes in Cauliflower (Brassica oleracea Botrytis L.)
Authors: Shafaqat Ali, Rehan Ahmad, Muhammad Rizwan
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Chromium (Cr) is one of the most toxic pollutants among heavy metals that adversely affect living organisms and physiological processes in plants. The present study investigated the effect of without and with 15 mg L-1 5-Aminolevulinic acid (ALA) on morpho-physiological attributes of cauliflower (Brassica oleracea botrytis L.) under different Cr concentrations (0, 10, 100 and 200 μM) in the growth medium. Results showed that Cr stress decreased the plant growth, biomass, photosynthetic pigments, and gas exchange characteristics. Chromium stress enhanced the activities of enzymatic antioxidants, catalase (CAT), superoxide dismutase (SOD), and guaiacol peroxidase (POD), and caused oxidative stress, as observed by increased level of malondialdehyde (MDA), hydrogen peroxide (H2O2), electrolyte leakage (EL), in both leaves and roots of cauliflower. Chromium concentrations and total Cr uptake increased in roots, stem and leaves of plants with increasing Cr levels in the growth medium. Foliar application of ALA increased plant growth, biomass, photosynthetic pigments and gas exchange characteristics under Cr stress as compared to without ALA application. As compared to Cr stress alone, ALA application decreased the levels of MDA, H2O2 and EL while further enhanced the activities of antioxidant enzymes in both leaves and roots. Chromium concentrations and total Cr uptake decreased by the ALA application as compared to without ALA. These results showed that foliar application of ALA might be effective in reducing Cr uptake and toxicity in cauliflower.Keywords: antioxidant enzymes, cauliflower, photosynthesis, chromium, ALA, hydrogen peroxide, electrolyte leakage
Procedia PDF Downloads 293354 Library Screening and Evaluation of Mycobacterium tuberculosis Ketol-Acid Reductoisomerase Inhibitors
Authors: Vagolu S. Krishna, Shan Zheng, Estharla M. Rekha, Luke W. Guddat, Dharmarajan Sriram
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Tuberculosis (TB) remains a major threat to human health. This due to the fact that current drug treatments are less than optimal as well as the rising occurrence of multi drug-resistant and extensively drug-resistant strains of the etiological agent, Mycobacterium tuberculosis (Mt). Given the wide-spread significance of this disease, we have undertaken a design and evaluation program to discover new anti-TB drug leads. Here, our attention is focused on ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway. Importantly, this enzyme is present in bacteria but not in humans, making it an attractive proposition for drug discovery. In the present work, we used high-throughput virtual screening to identify seventeen potential inhibitors of KARI using the Birla Institute of Technology and Science in-house database. Compounds were selected based on high docking scores, which were assigned as the result of favourable interactions between the compound and the active site of KARI. The Ki values for two leads, compounds 14 and 16 are 3.71 and 3.06 µM, respectively for Mt KARI. To assess the mode of binding, 100 ns molecular dynamics simulations for these two compounds in association with Mt KARI were performed and showed that the complex was stable with an average RMSD of less than 2.5 Å for all atoms. Compound 16 showed an MIC of 2.06 ± 0.91 µM and a 1.9 fold logarithmic reduction in the growth of Mt in an infected macrophage model. The two compounds exhibited low toxicity against murine macrophage RAW 264.7 cell lines. Thus, both compounds are promising candidates for development as an anti-TB drug leads.Keywords: ketol-acid reductoisomerase, macrophage, molecular docking and dynamics, tuberculosis
Procedia PDF Downloads 116353 A High Content Screening Platform for the Accurate Prediction of Nephrotoxicity
Authors: Sijing Xiong, Ran Su, Lit-Hsin Loo, Daniele Zink
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The kidney is a major target for toxic effects of drugs, industrial and environmental chemicals and other compounds. Typically, nephrotoxicity is detected late during drug development, and regulatory animal models could not solve this problem. Validated or accepted in silico or in vitro methods for the prediction of nephrotoxicity are not available. We have established the first and currently only pre-validated in vitro models for the accurate prediction of nephrotoxicity in humans and the first predictive platforms based on renal cells derived from human pluripotent stem cells. In order to further improve the efficiency of our predictive models, we recently developed a high content screening (HCS) platform. This platform employed automated imaging in combination with automated quantitative phenotypic profiling and machine learning methods. 129 image-based phenotypic features were analyzed with respect to their predictive performance in combination with 44 compounds with different chemical structures that included drugs, environmental and industrial chemicals and herbal and fungal compounds. The nephrotoxicity of these compounds in humans is well characterized. A combination of chromatin and cytoskeletal features resulted in high predictivity with respect to nephrotoxicity in humans. Test balanced accuracies of 82% or 89% were obtained with human primary or immortalized renal proximal tubular cells, respectively. Furthermore, our results revealed that a DNA damage response is commonly induced by different PTC-toxicants with diverse chemical structures and injury mechanisms. Together, the results show that the automated HCS platform allows efficient and accurate nephrotoxicity prediction for compounds with diverse chemical structures.Keywords: high content screening, in vitro models, nephrotoxicity, toxicity prediction
Procedia PDF Downloads 311352 A Systematic Review of the Antimicrobial Effects of Different Plant Extracts (Quercus infectoria) as Possible Candidates in the Treatment of Infectious Diseases
Authors: Sajjad Jafari
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Background and Aim: The use of herbal medicines has a long history. Today, due to the resistance of microorganisms to antibiotics and antimicrobial substances, herbal medicines have attracted attention due to their significant antimicrobial effects and low toxicity. This study aims to systematically review the antimicrobial effects of different plant extracts (Quercus infectoria) as possible candidates for treating infectious diseases. Material and Methods: The present study is a review study by searching reputable scientific databases such as PubMed, Google Scholar, Scopus, and Web of Science from 2000 to 2023 using the keywords Antimicrobial, Quercus infectoria, Medicinal herbal, Infectious diseases the latest information obtained. Results: In this study, 45 articles were found and reviewed. Quercus infectoria is a small tree native to Greece, Asia Minor, and Iran. Quercus is a plant genus in the family of Fagaceae. This species is generally known under the name ‘‘baloot” in Iran and is commonly used as a medicinal plant. The extracts used included water, hydro-alcoholic, ethanol, methanol. This plant had high inhibition activity and a lethal effect on gram-positive and gram-negative bacteria of ATCC strains, hospital, and resistant strains. Therefore, in addition to antibacterial effects, antiparasitic and antifungal effects. The seed of the plant was the most used and the most effective antimicrobial extract among the ethanol and methanol extracts. Conclusion: The findings of this study suggest that Quercus infectoria has significant antimicrobial effects against a wide range of microorganisms. This makes it a potential candidate for the development of new antimicrobial drugs. Further research is needed to confirm the efficacy and safety of Quercus infectoria in clinical trials.Keywords: antimicrobial, Quercus infectoria, medicinal herbal, infectious diseases
Procedia PDF Downloads 90351 A Retrospective Analysis of the Use of Vancomycin by Continous Infusion in the Critical Care Setting, Edinburgh
Authors: Sonia Nemakallu, Pota Kalima
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Introduction: Vancomycin is a glycopeptide antibiotic, commonly used to treat gram-positive bacteraemia. It has been increasingly used in the critical care setting due to an increased awareness of resistant gram positive organisms. In Edinburgh both tertiary hospitals, The Western General Hospital and The Royal Infirmary Of Edinburgh, commonly use Vancomycin for a variety of infections. Administration of Vancomyicn in these hospitals is by continuous infusion as it is thought to maintain serum concentrations easier and is a simpler monitoring system. Purpose: The aim of the study was to evaluate the efficacy and reliability in which Vancomycin is used. Material and Methods: A retrospective study, over a 6-month period from January 2014 to June 2014. 91 admissions were included, all received Vancomycin by continuous infusion during their critical care stay. Results: The number one use for Vancomycin in critical care settings was in the treatment of ventilator or hospital-acquired pneumonia. Only 3% of population had MRSA. 49% of admissions were not therapeutic on day 1 post loading dose. Of those that were therapeutic on day 1 post loading dose, 39% of admissions showed no organisms in any cultures taken, 42% had organisms sensitive to Vancomycin and 19% had only organisms resistant to Vancomycin. Those that were not therapeutic on day 1 showed similar organism sensitivities. 15% of admissions had Vancomycin levels above 25 (levels should be maintained between 15-25). An increase in creatinine was proportionally seen with an increase in Vancomycin levels. Conclusion: Within Edinburgh Vancomycin is being overused in the critical care setting with only 3% of the population having highly resistant organisms. Continuous infusion have not ruled out the complexity of maintaining therapeutic levels, with a large proportion of patients not being therapeutic on day 1. Further research is also required into the nephrotoxic effects of using higher doses of Vancomycin.Keywords: Vancomycin, continuous infusion, multi resistant organisms, sepsis, renal toxicity
Procedia PDF Downloads 450350 Binding Mechanism of Synthesized 5β-Dihydrocortisol and 5β-Dihydrocortisol Acetate with Human Serum Albumin to Understand Their Role in Breast Cancer
Authors: Monika Kallubai, Shreya Dubey, Rajagopal Subramanyam
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Our study is all about the biological interactions of synthesized 5β-dihydrocortisol (Dhc) and 5β-dihydrocortisol acetate (DhcA) molecules with carrier protein Human Serum Albumin (HSA). The cytotoxic study was performed on breast cancer cell line (MCF-7) normal human embryonic kidney cell line (HEK293), the IC50 values for MCF-7 cells were 28 and 25 µM, respectively, whereas no toxicity in terms of cell viability was observed with HEK293 cell line. The further experiment proved that Dhc and DhcA induced 35.6% and 37.7% early apoptotic cells and 2.5%, 2.9% late apoptotic cells respectively. Morphological observation of cell death through TUNEL assay revealed that Dhc and DhcA induced apoptosis in MCF-7 cells. The complexes of HSA–Dhc and HSA–DhcA were observed as static quenching, and the binding constants (K) was 4.7±0.03×104 M-1 and 3.9±0.05×104 M-1, and their binding free energies were found to be -6.4 and -6.16 kcal/mol, respectively. The displacement studies confirmed that lidocaine 1.4±0.05×104 M-1 replaced Dhc, and phenylbutazone 1.5±0.05×104 M-1 replaced by DhcA, which explains domain I and domain II are the binding sites for Dhc and DhcA. Further, CD results revealed that the secondary structure of HSA was altered in the presence of Dhc and DhcA. Furthermore, the atomic force microscopy and transmission electron microscopy showed that the dimensions like height and molecular sizes of the HSA–Dhc and HSA–DhcA complex were larger compared to HSA alone. Detailed analysis through molecular dynamics simulations also supported the greater stability of HSA–Dhc and HSA–DhcA complexes, and root-mean-square-fluctuation interpreted the binding site of Dhc as domain IB and domain IIA for DhcA. This information is valuable for the further development of steroid derivatives with improved pharmacological significance as novel anti-cancer drugs.Keywords: apoptosis, dihydrocortisol, fluorescence quenching, protein conformations
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