Search results for: dose volume histogram
3243 X-Ray Fluorescence Molecular Imaging with Improved Sensitivity for Biomedical Applications
Authors: Guohua Cao, Xu Dong
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X-ray Fluorescence Molecular Imaging (XFMI) holds great promise as a low-cost molecular imaging modality for biomedical applications with high chemical sensitivity. However, for in vivo biomedical applications, a key technical bottleneck is the relatively low chemical sensitivity of XFMI, especially at a reasonably low radiation dose. In laboratory x-ray source based XFMI, one of the main factors that limits the chemical sensitivity of XFMI is the scattered x-rays. We will present our latest findings on improving the chemical sensitivity of XFMI using excitation beam spectrum optimization. XFMI imaging experiments on two mouse-sized phantoms were conducted at three different excitation beam spectra. Our results show that the minimum detectable concentration (MDC) of iodine can be readily increased by five times via excitation spectrum optimization. Findings from this investigation could find use for in vivo pre-clinical small-animal XFMI in the future.Keywords: molecular imaging, X-ray fluorescence, chemical sensitivity, X-ray scattering
Procedia PDF Downloads 1863242 Compressive Strength of Synthetic Fiber Reinforced Concretes
Authors: Soner Guler, Demet Yavuz, Fuat Korkut
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Synthetic fibers are commonly used in many civil engineering applications because of its some superior characteristics such as non-corrosive and cheapness. This study presents the results of experimental study on compressive strength of synthetic fiber reinforced concretes. Two types of polyamide (PA) synthetic fiber with the length of 12 and 54 mm are used for this study. The fiber volume ratio is kept as 0.25%, 0.75%, and 0.75% in all mixes. The plain concrete compressive strength is 36.2 MPa. The test results clearly show that the increase in compressive strength for synthetic fiber reinforced concretes is significant. The greatest increase in compressive strength is 23% for PA synthetic fiber reinforced concretes with 0.75% fiber volume.Keywords: synthetic fibers, polyamide fibers, fiber volume, compressive strength
Procedia PDF Downloads 5273241 Optimum Design for Cathode Microstructure of Solid Oxide Fuel Cell
Authors: M. Riazat, H. Abdolvand, M. Baniassadi
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In this present work, 3D reconstruction of cathode of SOFC is developed with various volume fractions and porosity. Three Phase Boundary (TPB) of construction of such derived micro structures is calculated. The neural network is used to optimize the porosity and volume fraction of each phase to reach a structure with maximum TPB.Keywords: fuel cell, solid oxide, TPB, 3D reconstruction
Procedia PDF Downloads 3243240 Puereria mirifica Replacement Improves Skeletal Muscle Performance Associated with Increasing Parvalbumin Levels in Ovariectomized Rat
Authors: Uraporn Vongvatcharanon, Kochakorn Sukjan, Wandee Udomuksorn, Ekkasit Kumarnsit, Surapong Vongvatcharanon
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Sarcopenia is a loss of muscle mass, and strength frequently found in menopause. Estrogen replacement has been shown to improve such a loss of muscle functions. However, there is an increased risk of cancer that has to be considered because of the estrogen replacement therapy. Thus, phytoestrogen supplementation has been suggested as an alternative therapy. Pueraria mirifica (PM) is a plant in the family Leguminosae, that is known to be phytoestrogen-rich and has been traditionally used for the treatment of menopausal symptoms. It contains isoflavones and other compounds such as miroestrol and its derivatives. Parvalbumin (PV) is a calcium binding protein and functions as a relaxing factor in fast twitch muscle fibers. A decrease of the PV level results in a reduction of the speed of the twitch relaxation. Therefore, this study aimed to investigate the effect of an ethanolic extract from Pueraria mirifica on the estrogen levels, skeletal muscle functions and PV levels in the extensor digitorum longus (EDL) and gastrocnemius of ovariectomized rats. Twelve-week old female Wistar rats (200-250 g) were divided into 6 groups: SHAM (un-ovariectomized rats, that received double distilled water), PM-0 (ovariectomized rats, OVX, receiving double distilled water), E (OVX, receiving an estradiol benzoate dose of 0.04 mg/kg), PM-50 (OVX receiving PM 50 mg/kg), PM-500 (OVX receiving PM 500 mg/kg), PM-1000 (OVX receiving PM 1000 mg/kg) all for 90 days. The PM-0 group had estrogen levels, uterus weights, muscle mass, myofiber cross-section areas, peak tension, fatigue resistance, speed of relaxation and parvalbumin levels of both EDL and gastrocnemius that were significantly reduced compared to those of the SHAM group (p<0.05). Also the α and β estrogen receptor immunoreactivities and the parvalbumin immunoreactivities of both EDL and gastrocnemius were decreased in the PM-0 group. In contrast the E, PM-50, PM-500 and PM-1000 group had estrogen levels, uterus weights, muscle mass, myofiber cross-section areas, peak tension, fatigue resistance, speed of relaxation of both EDL and gastrocnemius that were significantly increased compared with PM-0 group (p<0.05). In addition, the α and β estrogen receptor immunoreactivities and parvalbumin immunoreactivity of both the EDL and gastrocnemius were increased in the E, PM-50, PM-500 and PM-1000 group. In addition the extract of Pueraria mirifica replacement group at 50 and 500 mg/kg had significantly increased parvalbumin levels in the EDL muscle but in the gastrocnemius, only the dose of 500 mg/kg increased the parvalbumin levels (p<0.05). These results have demonstrated that the use of the Pueraria mirifica extract as a replacement therapy for estrogen produced estrogenic activity that was similar to that produced by the estradiol benzoate replacement. It seems that the phytoestrogens could bind with the estrogen receptors and stimulate the transcriptional activity to synthesise muscle protein that caused an increase in muscle mass and parvalbumin levels. Thus, muscle synthesis may restore parvalbumin levels resulting in an enhanced relaxation efficiency that would lead to a shortened latent period before the next contraction.Keywords: Puereria mirifica, Parvalbumin, estrogen, ovariectomized rats
Procedia PDF Downloads 3823239 Attenuation of Homocysteine-Induced Cyclooxygenase-2 Expression in Human Monocytes by Fulvic Acid
Authors: Shao-Ju Chien, Yi-Chien Wu, Ting-Ying Huang, Li-Tsen Li, You-Jin Chen, Cheng-Nan Chen
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Homocysteine and pro-inflammatory mediators such as cyclooxygenase-2 (COX-2) have been linked to vascular dysfunction and risks of cardiovascular diseases. Fulvic acid (FA) is class of compounds of humic substances and possesses various pharmacological properties. However, the effect of FA on inflammatory responses of the monocytes remains unclear. We investigated the regulatory effect of FA on homocysteine-induced COX-2 expression in human monocytes. Peripheral blood monocytes and U937 cells were kept as controls or pre-treated with FA, and then stimulated with homocysteine. The results show that pretreating monocytes with FA inhibited the homocysteine-induced COX-2 expression in a dose-dependent manner. The inhibitor for nuclear factor-kB (NF-kB) attenuated homocysteine-induced COX-2 expression. Our findings provide a molecular mechanism by which FA inhibit homocysteine-induced COX-2 expression in monocytes, and a basis for using FA in pharmaceutical therapy against inflammation.Keywords: homocysteine, monocytes, cyclooxygenase-2, fulvic acid, anti-inflammation
Procedia PDF Downloads 5973238 β-Lactamase Inhibitory Effects of Anchusa azurea Extracts
Authors: Naoual Boussoualim, Hayat Trabsa, Iman Krache, Lekhmici Arrar, Abderrahmane Baghiani
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Resistance to antibiotics has emerged following their widespread use; the important mechanism of beta-lactam resistance in bacteria is the production of beta-lactamase. In order to find new bioactive beta-lactamase inhibitors, this study investigated the inhibition effect of the extracts of Anchusa azurea (AA) on a beta-lactamase from Bacillus cereus. The extracts exerted inhibitory effects on beta-lactamase in a dose-dependent manner, the results showed that the crude extract (BrE) and the ethyl acetate extract (AcE) of Anchusa azurea showed a very high inhibitory activity at a concentration of 10 mg, the percentage of inhibition was between 58% and 68%. Not all extracts were as potent as the original inhibitors such as clavulanic acid, the isolation and the structural elucidation of the active constituents in these extracts will provide useful means in the development of beta -lactamase inhibitors.Keywords: Anchusa azurea, natural product, resistance, antibiotics, beta-lactamase, inhibitors
Procedia PDF Downloads 5113237 The Influence of Carbamazepine on the Activity of CYP3A4 in Patients with Alcoholism
Authors: Mikhail S. Zastrozhin, Valery V. Smirnov, Dmitry A. Sychev, Ludmila M. Savchenko, Evgeny A. Bryun, Mark O. Nechaev
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Cytochrome P-450 isoenzyme 3A4 takes part in the biotransformation of medical drugs. The activity of CYP isoenzymes depends on genetic (polymorphisms of genes which encoded it) and phenotypic factors (a kind of food, a concomitant drug therapy). The aim of the study was to evaluate a carbamazepine effect on the CYP3A4 activity in patients with alcohol addiction. The study included 25 men with alcohol dependence, who received haloperidol during the exacerbation of the addiction. CYP3A4 activity was assessed by urinary 6-beta-hydroxycortisol/cortisol ratios measured by high performance liquid chromatography with mass spectrometry. The study modeled a graph and an equation of the logarithmic regression, that reflects the dependence of CYP3A4 activity on a dose of carbamazepine: y = 5,5 * 9,1 * 10-5 * x2. The study statistically significant demonstrates the effect of carbamazepine on CYP2D6 isozyme activity in patients with alcohol addiction.Keywords: CYP3A4, biotransformation, carbamazepine, alcohol abuse
Procedia PDF Downloads 2773236 Cooling Profile Analysis of Hot Strip Coil Using Finite Volume Method
Authors: Subhamita Chakraborty, Shubhabrata Datta, Sujay Kumar Mukherjea, Partha Protim Chattopadhyay
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Manufacturing of multiphase high strength steel in hot strip mill have drawn significant attention due to the possibility of forming low temperature transformation product of austenite under continuous cooling condition. In such endeavor, reliable prediction of temperature profile of hot strip coil is essential in order to accesses the evolution of microstructure at different location of hot strip coil, on the basis of corresponding Continuous Cooling Transformation (CCT) diagram. Temperature distribution profile of the hot strip coil has been determined by using finite volume method (FVM) vis-à-vis finite difference method (FDM). It has been demonstrated that FVM offer greater computational reliability in estimation of contact pressure distribution and hence the temperature distribution for curved and irregular profiles, owing to the flexibility in selection of grid geometry and discrete point position, Moreover, use of finite volume concept allows enforcing the conservation of mass, momentum and energy, leading to enhanced accuracy of prediction.Keywords: simulation, modeling, thermal analysis, coil cooling, contact pressure, finite volume method
Procedia PDF Downloads 4733235 The Hidden Mechanism beyond Ginger (Zingiber officinale Rosc.) Potent in vivo and in vitro Anti-Inflammatory Activity
Authors: Shahira M. Ezzat, Marwa I. Ezzat, Mona M. Okba, Esther T. Menze, Ashraf B. Abdel-Naim, Shahnas O. Mohamed
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Background: In order to decrease the burden of the high cost of synthetic drugs, it is important to focus on phytopharmaceuticals. The aim of our study was to search for the mechanism of ginger (Zingiber officinale Roscoe) anti-inflammatory potential and to correlate it to its biophytochemicals. Methods: Various extracts viz. water, 50%, 70%, 80%, and 90% ethanol were prepared from ginger rhizomes. Fractionation of the aqueous extract (AE) was accomplished using Diaion HP-20. In vitro anti-inflammatory activity of the different extracts and isolated compounds was evaluated by protein denaturation inhibition, membrane stabilization, protease inhibition, and anti-lipoxygenase assays. In vivo anti-inflammatory activity of AE was estimated by assessment of rat paw oedema after carrageenan injection. Prostaglandin E2 (PGE2), certain inflammation markers (TNF-α, IL-6, IL-1α, IL-1β, INFr, MCP-1MIP, RANTES, and Nox) levels and MPO activity in the paw edema exudates were measured. Total antioxidant capacity (TAC) was also determined. Histopathological alterations of paw tissues were scored. Results: All the tested extracts showed significant (p < 0.1) anti-inflammatory activities. The highest percentage of heat induced albumin denaturation (66%) was exhibited by the 50% ethanol (250 μg/ml). The 70 and 90% ethanol extracts (500 μg/ml) were more potent as membrane stabilizers (34.5 and 37%, respectively) than diclofenac (33%). The 80 and 90% ethanol extracts (500 μg/ml) showed maximum protease inhibition (56%). The strongest anti-lipoxygenase activity was observed for the AE. It showed more significant lipoxygenase inhibition activity than that of diclofenac (58% and 52%, respectively) at the same concentration (125 μg/ml). Fractionation of AE yielded four main fractions (Fr I-IV) which showed significant in vitro anti-inflammatory. Purification of Fr-III and IV led to the isolation of 6-poradol (G1), 6-shogaol (G2); methyl 6- gingerol (G3), 5-gingerol (G4), 6-gingerol (G5), 8-gingerol (G6), 10-gingerol (G7), and 1-dehydro-6-gingerol (G8). G2 (62.5 ug/ml), G1 (250 ug/ml), and G8 (250 ug/ml) exhibited potent anti-inflammatory activity in all studied assays, while G4 and G5 exhibited moderate activity. In vivo administration of AE ameliorated rat paw oedema in a dose-dependent manner. AE (at 200 mg/kg) showed significant reduction (60%) of PGE2 production. The AE at different doses (at 25-200 mg/kg) showed significant reduction in inflammatory markers except for IL-1α. AE (at 25 mg/kg) is superior to indomethacin in reduction of IL-1β. Treatment of animals with the AE (100, 200 mg/kg) or indomethacin (10 mg/kg) showed significant reduction in TNF-α, IL-6, MCP-1, and RANTES levels, and MPO activity by about (31, 57 and 32% ) (65, 60 and 57%) (27, 41 and 28%) (23, 32 and 23%) (66, 67 and 67%) respectively. AE at 100 and 200 mg/kg was equipotent to indomethacin in reduction of NOₓ level and in increasing the TAC. Histopathological examination revealed very few inflammatory cells infiltration and oedema after administration of AE (200 mg/kg) prior to carrageenan. Conclusion: Ginger anti-inflammatory activity is mediated by inhibiting macrophage and neutrophils activation as well as negatively affecting monocyte and leukocyte migration. Moreover, it produced dose-dependent decrease in pro-inflammatory cytokines and chemokines and replenished the total antioxidant capacity. We strongly recommend future investigations of ginger in the potential signal transduction pathways.Keywords: anti-lipoxygenase activity, inflammatory markers, 1-dehydro-6-gingerol, 6-shogaol
Procedia PDF Downloads 2523234 MTT Assay-Guided Isolation of a Cytotoxic Lead from Hedyotis umbellata and Its Mechanism of Action against Non-Small Cell Lung Cancer A549 Cells
Authors: Kirti Hira, A. Sajeli Begum, S. Mahibalan, Poorna Chandra Rao
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Introduction: Cancer is one of the leading causes of death worldwide. Although existing therapy effectively kills cancer cells, they do affect normal growing cells leading to many undesirable side effects. Hence there is need to develop effective as well as safe drug molecules to combat cancer, which is possible through phyto-research. The currently available plant-derived blockbuster drugs are the example for this. In view of this, an investigation was done to identify cytotoxic lead molecules from Hedyotis umbellata (Family Rubiaceae), a widely distributed weed in India. Materials and Methods: The methanolic extract of the whole plant of H. umbellata (MHU), prepared through Soxhlet extraction method was further fractionated with diethyl ether and n-butanol, successively. MHU, ether fraction (EMHU) and butanol fraction (BMHU) were lyophilized and were tested for the cytotoxic effect using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay against non-small cell lung cancer (NSCLC) A549 cell lines. The potentially active EMHU was subjected to chromatographic purification using normal-phase silica columns, in order to isolate the responsible bioactive compounds. The isolated pure compounds were tested for their cytotoxic effect by MTT assay against A549 cells. Compound-3, which was found to be most active, was characterized using IR, 1H- and 13C-NMR and MS analysis. The study was further extended to decipher the mechanism of action of cytotoxicity of compound-3 against A549 cells through various in vitro cellular models. Cell cycle analysis was done using flow cytometry following PI (Propidium Iodide) staining. Protein analysis was done using Western blot technique. Results: Among MHU, EMHU, and BMHU, the non-polar fraction EMHU demonstrated a significant dose-dependent cytotoxic effect with IC50 of 67.7μg/ml. Chromatography of EMHU yielded seven compounds. MTT assay of isolated compounds explored compound-3 as potentially active one, which inhibited the growth of A549 cells with IC50value of 14.2μM. Further, compound-3 was identified as cedrelopsin, a coumarin derivative having molecular weight of 260. Results of in vitro mechanistic studies explained that cedrelopsin induced cell cycle arrest at G2/M phase and down-regulated the expression of G2/M regulatory proteins such as cyclin B1, cdc2, and cdc25C, dose dependently. This is the first report that explores the cytotoxic mechanism of cedrelopsin. Conclusion: Thus a potential small lead molecule, cedrelopsin isolated from H. umbellata, showing antiproliferative effect mediated by G2/M arrest in A549 cells was discovered. The effect of cedrelopsin against other cancer cell lines followed by in vivo studies can be performed in future to develop a new drug candidate.Keywords: A549, cedrelopsin, G2/M phase, Hedyotis umbellata
Procedia PDF Downloads 1753233 The Effect of Clover Honey Supplementation on the Anthropometric Measurements and Lipid Profile of Malnourished Infants and Children
Authors: Bassma A. Abdelhaleem, Mamdouh A. Abdulrhman, Nagwa I. Mohamed
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Malnutrition in children is an increasing problem worldwide which may result in both short and long-term irreversible negative health outcomes. Severe Acute Malnutrition (SAM) affects more than 18 million children each year, mostly living in low-income settings. SAM contributes to 45% of all deaths in children less than five years of age. Honey is a natural sweetener, containing mainly monosaccharides (up to 80%), disaccharides (3–5%), water (17–20%), and a wide range of minor constituents such as vitamins, minerals, proteins, amino acids, enzymes, and phytochemicals, mainly phenolic acids, and flavonoids. Honey has been used in many cultures around the world due to its known nutritional and medicinal benefits including the treatment of hypercholesterolemia. Despite its use since ancient times yet little is known about its potential benefits for malnourished children. Honey has the potential to be an affordable solution for malnourished low-income children as it is nutrient-dense and calorie dense food, easily absorbed, highly palatable, enhances appetite, and boosts immunity. This study assessed the effect of clover honey supplementation on the anthropometric measurements and lipid profile of malnourished infants and children. A prospective interventional clinical trial was conducted between November 2019 to November 2020, on 40 malnourished infants and children divided into two groups: Group A (20 children; 11 males and 9 females) received honey in a dose of 1.75ml/kg/dose, twice weekly for 12 weeks and Group B (20 children; 6 males and 14 females) received placebo. Written informed consent was obtained for parents/guardians. Patients were recruited from the Pediatric Nutrition Clinic at Ain Shams University. Anthropometric measurements (weight, height, body mass index, head circumference, and mid-arm circumference) and fasting serum cholesterol levels were measured at baseline and after 3 months. The 3-month honey consumption had a statistically highly significant effect on increasing weight, height, and body mass index and lowering fasting serum cholesterol levels in primary malnourished infants and children. Weight, height, body mass index, and fasting serum cholesterol level before honey consumption were (9.49 ± 2.03, 81.45 ± 8.31, 14.24 ± 2.15, 178.00 ± 20.91) and after 3 months of honey consumption were (10.91 ± 2.11, 84.80 ± 8.23, 15.07 ± 2.05, 162.45 ± 19.73) respectively with P-value < 0.01. Our results showed a significant desirable effect of honey consumption on changes in nutritional status based on weight, height, and body mass index, and has a favourable effect on lowering fasting serum cholesterol levels. These results propose the use of honey as an affordable solution to improve malnutrition, particularly in low-income countries. However, further research needs to weigh benefits against potential harms including the risk of botulinum toxin that is historically associated with honey consumption in early childhood.Keywords: clinical trial, dyslipidemia, honey, malnutrition
Procedia PDF Downloads 1083232 Formulation and Evaluation of Dispersible Tablet of Furosemide for Pediatric Use
Authors: O. Benaziz, A. Dorbane, S. Djeraba
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The objective of this work is to formulate a dry dispersible form of furosemide in the context of pediatric dose adjustment. To achieve this, we have produced a set of formulas that will be tested in process and after compression. The formula with the best results will be improved to optimize the final shape of the product. Furosemide is the most widely used pediatric diuretic because of its low toxicity. The manufacturing process was chosen taking into account all the data relating to the active ingredient and the excipients used and complying with the specifications and requirements of dispersible tablets. The process used to prepare these tablets was wet granulation. Different excipients were used: lactose, maize starch, magnesium stearate and two superdisintegrants. The mode of incorporation of super-disintegrant changes with each formula. The use of super-disintegrant in the formula allowed optimization of the disintegration time. Prepared tablets were evaluated for weight, content uniformity, hardness, disintegration time, friability and in vitro dissolution test.Keywords: formulation, dispersible tablets, wet granulation, superdisintegrants, disintegration
Procedia PDF Downloads 3453231 Movement of Metallic Inclusions in the Volume of Synthetic Diamonds at High Pressure and High Temperature in the Temperature Gradient Field
Authors: P. I. Yachevskaya, S. A. Terentiev, M. S. Kuznetsov
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Several synthetic HPHT diamonds with metal inclusions have been studied. To have possibility of investigate the movement and transformation of the inclusions in the volume of the diamond the samples parallele-piped like shape has been made out of diamond crystals. The calculated value of temperature gradient in the samples of diamond which was placed in high-pressure cell was about 5-10 grad/mm. Duration of the experiments was in range 2-16 hours. All samples were treated several times. It has been found that the volume (dimensions) of inclusions, temperature, temperature gradient and the crystallographic orientation of the samples in the temperature field affects the movement speed of inclusions. Maximum speed of inclusions’ movement reached a value 150 µm/h.Keywords: diamond, inclusions, temperature gradient, HPHT
Procedia PDF Downloads 5103230 Effectiveness of Radon Remedial Action Implemented in a School on the Island of Ischia
Authors: F. Loffredo, M. Quarto, M. Pugliese, A. Mazzella, F. De Cicco, V. Roca
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The aim of this study is to evaluate the efficacy of radon remedial action in a school on the Ischia island, South Italy, affected by indoor radon concentration higher than the value of 500 Bq/m3. This value is the limit imposed by the Italian legislation, to above which corrective actions in schools are necessary. Before the application of remedial action, indoor radon concentrations were measured in 9 rooms of the school. The measurements were performed with LR-115 passive alpha detectors (SSNTDs) and E-Perm. The remedial action was conducted in one of the office affected by high radon concentration using a Radonstop paint applied after the construction of a concrete slab under the floor. The effect of remedial action was the reduction of the concentration of radon of 41% and moreover it has demonstrated to be durable over time. The chosen method is cheap and easy to apply and it could be designed for various types of building. This method can be applied to new and existing buildings that show high dose values.Keywords: E-Perm, LR 115 detectors, radon remediation, school
Procedia PDF Downloads 2293229 Numerical Study of Natural Convection of a Localized Heat Source at the up of a Nanofluid-Filled Enclosure
Authors: Marziyeh Heydari, Hossein Shokouhmand
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This article presents a numerical study of natural convection of a heat source embedded on the up wall of an enclosure filled with nanofluid. The bottom and vertical walls of the enclosure are maintained at a relatively low temperature. The type of nanofluid and solid volume fraction of nanoparticle on the heat transfer performance is studied. The results indicated that adding nanoparticle into pure paraffin improves heat transfer. The results are presented over a wide range of Rayleigh numbers(Ra=〖10〗^3 〖-10〗^5), the volume fraction of nanoparticles (0≤ɸ≤0.4%). For an enclosure, the Nusselt number of a cu-paraffin nanofluid was reduced by increasing the volume fraction of nanoparticles above 0.2%.Keywords: nanofluid, heat transfer, heat source, enclosure
Procedia PDF Downloads 3103228 Gambusia an Excellent Indicator of Metals Stress
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The activity of acetylcholinesterase (AChE) was studied in freshwater fish exposed to two heavy metals lead and cadmium. Measurements were made after short exposures (4 and 7 days) at concentrations of 1, 5, and 7μg/L cadmium and 1.25, 2.25, and 5 mg/L of lead. Cadmium induced no significant increases in activity of AChE in the gills for the lowest dose. Except significant inhibition on 7 days. In muscle of Gambusia, under stress of metallic lead, the activity increases compared to the control are noted at 4 days of treatment and inhibitions to 7 days of exposure. The analysis of variance (time, treatment) indicates only a very significant time effect (p<0.05), and as for cadmium, a significant body effect (p<0.01) is recorded. This small fish sedentary, colonizing particularly quiet environments, polluted, can only be the ideal bioindicator of contamination and bioaccumulation of metals. The presence of lead and cadmium in the bodies of fish is a risk factor not only for the lives of these aquatic species, but also for the man who is the top predator at the end of the food chain.Keywords: biomarkers, bioindicator, environmenlal health, metals
Procedia PDF Downloads 4983227 A Numerical Method to Evaluate the Elastoplastic Material Properties of Fiber Reinforced Composite
Authors: M. Palizvan, M. H. Sadr, M. T. Abadi
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The representative volume element (RVE) plays a central role in the mechanics of random heterogeneous materials with a view to predicting their effective properties. In this paper, a computational homogenization methodology, developed to determine effective linear elastic properties of composite materials, is extended to predict the effective nonlinear elastoplastic response of long fiber reinforced composite. Finite element simulations of volumes of different sizes and fiber volume fractures are performed for calculation of the overall response RVE. The dependencies of the overall stress-strain curves on the number of fibers inside the RVE are studied in the 2D cases. Volume averaged stress-strain responses are generated from RVEs and compared with the finite element calculations available in the literature at moderate and high fiber volume fractions. For these materials, the existence of an RVE is demonstrated for the sizes of RVE corresponding to 10–100 times the diameter of the fibers. In addition, the response of small size RVE is found anisotropic, whereas the average of all large ones leads to recover the isotropic material properties.Keywords: homogenization, periodic boundary condition, elastoplastic properties, RVE
Procedia PDF Downloads 1533226 Protective Effect of Cinnamomum zeylanicum Bark Extract against Doxorubicin Induced Cardiotoxicity: A Preliminary Study
Authors: J. A. N. Sandamali, R. P. Hewawasam, K. A. P. W. Jayatilaka, L. K. B. Mudduwa
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Introduction: Doxorubicin is widely used in the treatment of solid organ tumors and hematological malignancies, but the dose-dependent cardiotoxicity due to free radical formation compromises its clinical utility. Therapeutic strategies which enhance cellular endogenous defense systems have been identified as promising approaches to combat oxidative stress-associated conditions. Cinnamomum zeylanicum (Ceylon cinnamon) has a number antioxidant compounds, which can effectively scavenge reactive oxygen including superoxide anions, hydroxyl radicals and as well as other free radicals. Therefore, the objective of the study was to elucidate the most effective dose of Cinnamomum bark extract which ameliorates doxorubicin-induced cardiotoxicity. Materials and methods: Wistar rats were divided into seven groups of 10 animals in each. Group 1: normal control (distilled water, orally, for 14 days, 10 mL/kg saline, ip, after 16 hours fast on the 11th day); Group 2: doxorubicin control (distilled water, orally, for 14 days, 18 mg/kg doxorubicin, ip, after 16 hour fast on the 11th day); Groups 3-7: five doses of freeze dried aqueous bark extracts (0.125, 0.25, 0.5, 1.0, 2.0g/kg, orally, daily for 14 days, 18 mg/kg doxorubicin, ip, after 16 hours fast on the 11th day). Animals were sacrificed on the 15th day and blood was collected for the estimation of cardiac troponin I (cTnI), AST and LDH concentrations and myocardial tissues were collected for histopathological assessment of myocardial damage and irreversible changes were graded by developing a score. Results: cTnI concentration of groups 1-7 were 0, 161.9, 128.6, 95.9, 38, 19.41 & 12.36 pg/mL showing significant differences (p<0.05) between group 2 and groups 4-7. In groups 1-7, serum AST concentration were 26.82, 68.1, 37.18, 36.23, 26.8, 26.62 & 22.43U/L and LDH concentrations were 1166.13, 2428.84, 1658.35, 1474.34, 1277.58, 1110.21 & 974.40U/L and a significant difference (p<0.05) was observed between group 2 and groups 3-7. The maximum score for myocardial necrosis was observed in group 2. Parallel to the increase of the dosage of plant extract, a gradual reduction of the score for myocardial necrosis was observed in groups 3-7. Reversible histological changes such as vacuolation, congestion were observed in group 2 and all plant treated groups. Haemorrhages, inflammatory cell infiltrations, and interstitial oedema were observed in group 2, but absent in groups treated with higher doses of the plant extract. Discussion & Conclusion: According to the in vitro antioxidant assays performed, Cinnamomum zeylanicum (Ceylon cinnamon) bark possesses high amounts of polyphenolic substances and high antioxidant activity. The present study showed that Cinnamomum zeylanicum extract at 2.0 g/kg possesses the most significant cardioprotective effect against doxorubicin-induced cardiotoxicity. It can be postulated that pretreatment with Cinnamomum bark extract may replenish the cardiomyocytes with antioxidants that are needed for the defense against oxidative stress induced by doxorubicin.Keywords: cardioprotection, Cinnamomum zeylanicum, doxorubicin, free radicals
Procedia PDF Downloads 1623225 Application Use of Slaughterhouse Waste to Improve Nutrient Level in Apium glaviolens
Authors: Hasan Basri Jumin
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Using the slaughterhouse waste combined to suitable dose of nitrogen fertilizer to Apium glaviolen gives the significant effect to mean relative growth rate. The same pattern also showed significantly in net assimilation rate. The net assimilation rate increased significantly during 42 days old plants. Combination of treatment of 100 ml/l animal slaughterhouse waste and 0.1 g/kg nitrogen fertilizer/kg soil increased the vegetative growth of Apium glaviolens. The biomass of plant and mean relative growth rate of Apium glaviolens were rapidly increased in 4 weeks after planting and gradually decreased after 35 days at the harvest time. Combination of 100 ml/l slaughterhouse waste and applied 0.1 g/kg nitrogen fertilizer has increased all parameters. The highest vegetative growth, biomass, mean relative growth rate and net assimilation rate were received from 0.56 mg-l.m-2.days-1.Keywords: Apium glaviolent, nitrogen, pollutant, slaughterhouse, waste
Procedia PDF Downloads 3663224 Fucoidan: A Potent Seaweed-Derived Polysaccharide with Immunomodulatory and Anti-inflammatory Properties
Authors: Tauseef Ahmad, Muhammad Ishaq, Mathew Eapen, Ahyoung Park, Sam Karpiniec, Vanni Caruso, Rajaraman Eri
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Fucoidans are complex, fucose-rich sulfated polymers discovered in brown seaweeds. Fucoidans are popular around the world, particularly in the nutraceutical and pharmaceutical industries, due to their promising medicinal properties. Fucoidans have been shown to have a variety of biological activities, including anti-inflammatory effects. They are known to inhibit inflammatory processes through a variety of mechanisms, including enzyme inhibition and selectin blockade. Inflammation is a part of the complicated biological response of living systems to damaging stimuli, and it plays a role in the pathogenesis of a variety of disorders, including arthritis, inflammatory bowel disease, cancer, and allergies. In the current investigation, various fucoidan extracts from Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica were assessed for inhibition of pro-inflammatory cytokine production (TNF-α, IL-1β, and IL-6) in LPS induced human macrophage cell line (THP-1) and human peripheral blood mononuclear cells (PBMCs). Furthermore, we also sought to catalogue these extracts based on their anti-inflammatory effects in the current in-vitro cell model. Materials and Methods: To assess the cytotoxicity of fucoidan extracts, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5, -diphenyltetrazolium bromide) cell viability assay was performed. Furthermore, a dose-response for fucoidan extracts was performed in LPS induced THP-1 cells and PBMCs after pre-treatment for 24 hours, and levels of TNF-α, IL-1β, and IL-6 cytokines were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Results: The MTT cell viability assay demonstrated that fucoidan extracts exhibited no evidence of cytotoxicity in THP-1 cells or PBMCs after 48 hours of incubation. The results of the sandwich ELISA revealed that all fucoidan extracts suppressed cytokine production in LPS-stimulated PBMCs and human THP-1 cells in a dose-dependent manner. Notably, at lower concentrations, the lower molecular fucoidan (5-30 kDa) extract from Macrocystis pyrifera was a highly efficient inhibitor of pro-inflammatory cytokines. Fucoidan extracts from all species including Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica exhibited significant anti-inflammatory effects. These findings on several fucoidan extracts provide insight into strategies for improving their efficacy against inflammation-related diseases. Conclusion: In the current research, we have successfully catalogued several fucoidan extracts based on their efficiency in LPS-induced macrophages and PBMCs in downregulating the key pro-inflammatory cytokines (TNF-, IL-1 and IL-6), which are prospective targets in human inflammatory illnesses. Further research would provide more information on the mechanism of action, allowing it to be tested for therapeutic purposes as an anti-inflammatory medication.Keywords: fucoidan, PBMCs, THP-1, TNF-α, IL-1β, IL-6, inflammation
Procedia PDF Downloads 593223 Intelligent Swarm-Finding in Formation Control of Multi-Robots to Track a Moving Target
Authors: Anh Duc Dang, Joachim Horn
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This paper presents a new approach to control robots, which can quickly find their swarm while tracking a moving target through the obstacles of the environment. In this approach, an artificial potential field is generated between each free-robot and the virtual attractive point of the swarm. This artificial potential field will lead free-robots to their swarm. The swarm-finding of these free-robots dose not influence the general motion of their swarm and nor other robots. When one singular robot approaches the swarm then its swarm-search will finish, and it will further participate with its swarm to reach the position of the target. The connections between member-robots with their neighbours are controlled by the artificial attractive/repulsive force field between them to avoid collisions and keep the constant distances between them in ordered formation. The effectiveness of the proposed approach has been verified in simulations.Keywords: formation control, potential field method, obstacle avoidance, swarm intelligence, multi-agent systems
Procedia PDF Downloads 4403222 Comparison of the Chest X-Ray and Computerized Tomography Scans Requested from the Emergency Department
Authors: Sahabettin Mete, Abdullah C. Hocagil, Hilal Hocagil, Volkan Ulker, Hasan C. Taskin
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Objectives and Goals: An emergency department is a place where people can come for a multitude of reasons 24 hours a day. As it is an easy, accessible place, thanks to self-sacrificing people who work in emergency departments. But the workload and overcrowding of emergency departments are increasing day by day. Under these circumstances, it is important to choose a quick, easily accessible and effective test for diagnosis. This results in laboratory and imaging tests being more than 40% of all emergency department costs. Despite all of the technological advances in imaging methods and available computerized tomography (CT), chest X-ray, the older imaging method, has not lost its appeal and effectiveness for nearly all emergency physicians. Progress in imaging methods are very convenient, but physicians should consider the radiation dose, cost, and effectiveness, as well as imaging methods to be carefully selected and used. The aim of the study was to investigate the effectiveness of chest X-ray in immediate diagnosis against the advancing technology by comparing chest X-ray and chest CT scan results of the patients in the emergency department. Methods: Patients who applied to Bulent Ecevit University Faculty of Medicine’s emergency department were investigated retrospectively in between 1 September 2014 and 28 February 2015. Data were obtained via MIAMED (Clear Canvas Image Server v6.2, Toronto, Canada), information management system which patients’ files are saved electronically in the clinic, and were retrospectively scanned. The study included 199 patients who were 18 or older, had both chest X-ray and chest CT imaging. Chest X-ray images were evaluated by the emergency medicine senior assistant in the emergency department, and the findings were saved to the study form. CT findings were obtained from already reported data by radiology department in the clinic. Chest X-ray was evaluated with seven questions in terms of technique and dose adequacy. Patients’ age, gender, application complaints, comorbid diseases, vital signs, physical examination findings, diagnosis, chest X-ray findings and chest CT findings were evaluated. Data saved and statistical analyses have made via using SPSS 19.0 for Windows. And the value of p < 0.05 were accepted statistically significant. Results: 199 patients were included in the study. In 38,2% (n=76) of all patients were diagnosed with pneumonia and it was the most common diagnosis. The chest X-ray imaging technique was appropriate in patients with the rate of 31% (n=62) of all patients. There was not any statistically significant difference (p > 0.05) between both imaging methods (chest X-ray and chest CT) in terms of determining the rates of displacement of the trachea, pneumothorax, parenchymal consolidation, increased cardiothoracic ratio, lymphadenopathy, diaphragmatic hernia, free air levels in the abdomen (in sections including the image), pleural thickening, parenchymal cyst, parenchymal mass, parenchymal cavity, parenchymal atelectasis and bone fractures. Conclusions: When imaging findings, showing cases that needed to be quickly diagnosed, were investigated, chest X-ray and chest CT findings were matched at a high rate in patients with an appropriate imaging technique. However, chest X-rays, evaluated in the emergency department, were frequently taken with an inappropriate technique.Keywords: chest x-ray, chest computerized tomography, chest imaging, emergency department
Procedia PDF Downloads 1923221 Characterization of N+C, Ti+N and Ti+C Ion Implantation into Ti6Al4V Alloy
Authors: Xingguo Feng, Hui Zhou, Kaifeng Zhang, Zhao Jiang, Hanjun Hu, Jun Zheng, Hong Hao
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TiN and TiC films have been prepared on Ti6Al4V alloy substrates by plasma-based ion implantation. The effect of N+C and Ti+N hybrid ion implantation at 50 kV, and Ti+C hybrid ion implantation at 20 kV, 35 kV and 50 kV extraction voltages on mechanical properties at a dose of 2×10¹⁷ ions / cm² was studied. The chemical states and microstructures of the implanted samples were investigated using X-ray photoelectron (XPS), and X-ray diffraction (XRD), together with the mechanical and tribological properties of the samples were characterized using nano-indentation and ball-on-disk tribometer. It was found that the modified layer by Ti+C implanted at 50 kV was composed of mainly TiC and Ti-O bond and the layer of Ti+N implanted at 50 kV was observed to be TiN and Ti-O bond. Hardness tests have shown that the hardness values for N+C, Ti+N, and Ti+C hybrid ion implantation samples were much higher than the un-implanted ones. The results of wear tests showed that both Ti+C and Ti+N ion implanted samples had much better wear resistance compared un-implanted sample. The wear rate of Ti+C implanted at 50 kV sample was 6.7×10⁻⁵mm³ / N.m, which was decreased over one order than unimplanted samples.Keywords: plasma ion implantation, x-ray photoelectron (XPS), hardness, wear
Procedia PDF Downloads 4103220 The Effect of Manure Loaded Biochar on Soil Microbial Communities
Authors: T. Weber, D. MacKenzie
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The script in this paper describes the use of advanced simulation environment using electronic systems (microcontroller, operational amplifiers, and FPGA). The simulation was used for non-linear dynamic systems behaviour with required observer structure working with parallel real-time simulation based on state-space representation. The proposed deposited model was used for electrodynamic effects including ionising effects and eddy current distribution also. With the script and proposed method, it is possible to calculate the spatial distribution of the electromagnetic fields in real-time and such systems. For further purpose, the spatial temperature distribution may also be used. With upon system, the uncertainties and disturbances may be determined. This provides the estimation of the more precise system states for the required system and additionally the estimation of the ionising disturbances that arise due to radiation effects in space systems. The results have also shown that a system can be developed specifically with the real-time calculation (estimation) of the radiation effects only. Electronic systems can take damage caused by impacts with charged particle flux in space or radiation environment. TID (Total Ionising Dose) of 1 Gy and Single Effect Transient (SET) free operation up to 50 MeVcm²/mg may assure certain functions. Single-Event Latch-up (SEL) results on the placement of several transistors in the shared substrate of an integrated circuit; ionising radiation can activate an additional parasitic thyristor. This short circuit between semiconductor-elements can destroy the device without protection and measurements. Single-Event Burnout (SEB) on the other hand, increases current between drain and source of a MOSFET and destroys the component in a short time. A Single-Event Gate Rupture (SEGR) can destroy a dielectric of semiconductor also. In order to be able to react to these processes, it must be calculated within a shorter time that ionizing radiation and dose is present. For this purpose, sensors may be used for the realistic evaluation of the diffusion and ionizing effects of the test system. For this purpose, the Peltier element is used for the evaluation of the dynamic temperature increases (dT/dt), from which a measure of the ionization processes and thus radiation will be detected. In addition, the piezo element may be used to record highly dynamic vibrations and oscillations to absorb impacts of charged particle flux. All available sensors shall be used to calibrate the spatial distributions also. By measured value of size and known location of the sensors, the entire distribution in space can be calculated retroactively or more accurately. With the formation, the type of ionisation and the direct effect to the systems and thus possible prevent processes can be activated up to the shutdown. The results show possibilities to perform more qualitative and faster simulations independent of space-systems and radiation environment also. The paper gives additionally an overview of the diffusion effects and their mechanisms.Keywords: cattle, biochar, manure, microbial activity
Procedia PDF Downloads 1033219 An Open Loop Distribution Module for Precise and Uniform Drip Fertigation in Soilless Culture
Authors: Juan Ignacio Arango, Andres Diaz, Giacomo Barbieri
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In soilless culture, the definition of efficient fertigation strategies is fundamental for the growth of crops. Flexible test-benches able to independently manage groups of crops are key for investigating efficient fertigation practices through experimentation. These test-benches must be able to provide nutrient solution (NS) in a precise, uniform and repeatable way in order to effectively implement and compare different fertigation strategies. This article describes a distribution module for investigating fertigation practices able to control the fertigation dose and frequency. The proposed solution is characterized in terms of precision, uniformity and repeatability since these parameters are fundamental in the implementation of effective experiments for the investigation of fertigation practices. After a calibration process, the implemented system reaches a precision of 1mL, a uniformity of 98.5% at a total cost of 735USD.Keywords: recision horticulture, test-bench, fertigation strategy, automation, flexibility
Procedia PDF Downloads 1393218 Insight into Enhancement of CO2 Capture by Clay Minerals
Authors: Mardin Abdalqadir, Paul Adzakro, Tannaz Pak, Sina Rezaei Gomari
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Climate change and global warming recently became significant concerns due to the massive emissions of greenhouse gases into the atmosphere, predominantly CO2 gases. Therefore, it is necessary to find sustainable and inexpensive methods to capture the greenhouse gasses and protect the environment for live species. The application of naturally available and cheap adsorbents of carbon such as clay minerals became a great interest. However, the minerals prone to low storage capacity despite their high affinity to adsorb carbon. This paper aims to explore ways to improve the pore volume and surface area of two selected clay minerals, ‘montmorillonite and kaolinite’ by acid treatment to overcome their low storage capacity. Montmorillonite and kaolinite samples were treated with different sulfuric acid concentrations (0.5, 1.2 and 2.5 M) at 40 °C for 8 hours to achieve the above aim. The grain size distribution and morphology of clay minerals before and after acid treatment were explored with Scanning Electron Microscope to evaluate surface area improvement. The ImageJ software was used to find the porosity and pore volume of treated and untreated clay samples. The structure of the clay minerals was also analyzed using an X-ray Diffraction machine. The results showed that the pore volume and surface area were increased substantially through acid treatment, which speeded up the rate of carbon dioxide adsorption. XRD pattern of kaolinite did not change after sulfuric acid treatment, which indicates that acid treatment would not affect the structure of kaolinite. It was also discovered that kaolinite had a higher pore volume and porosity than montmorillonite before and after acid treatment. For example, the pore volume of untreated kaolinite was equal to 30.498 um3 with a porosity of 23.49%. Raising the concentration of acid from 0.5 M to 2.5 M in 8 hours’ time reaction led to increased pore volume from 30.498 um3 to 34.73 um3. The pore volume of raw montmorillonite was equal to 15.610 um3 with a porosity of 12.7%. When the acid concentration was raised from 0.5 M to 2.5 M for the same reaction time, pore volume also increased from 15.610 um3 to 20.538 um3. However, montmorillonite had a higher specific surface area than kaolinite. This study concludes that clay minerals are inexpensive and available material sources to model the realistic conditions and apply the results of carbon capture to prevent global warming, which is one of the most critical and urgent problems in the world.Keywords: acid treatment, kaolinite, montmorillonite, pore volume, porosity, surface area
Procedia PDF Downloads 1693217 Adaptation of Projection Profile Algorithm for Skewed Handwritten Text Line Detection
Authors: Kayode A. Olaniyi, Tola. M. Osifeko, Adeola A. Ogunleye
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Text line segmentation is an important step in document image processing. It represents a labeling process that assigns the same label using distance metric probability to spatially aligned units. Text line detection techniques have successfully been implemented mainly in printed documents. However, processing of the handwritten texts especially unconstrained documents has remained a key problem. This is because the unconstrained hand-written text lines are often not uniformly skewed. The spaces between text lines may not be obvious, complicated by the nature of handwriting and, overlapping ascenders and/or descenders of some characters. Hence, text lines detection and segmentation represents a leading challenge in handwritten document image processing. Text line detection methods that rely on the traditional global projection profile of the text document cannot efficiently confront with the problem of variable skew angles between different text lines. Hence, the formulation of a horizontal line as a separator is often not efficient. This paper presents a technique to segment a handwritten document into distinct lines of text. The proposed algorithm starts, by partitioning the initial text image into columns, across its width into chunks of about 5% each. At each vertical strip of 5%, the histogram of horizontal runs is projected. We have worked with the assumption that text appearing in a single strip is almost parallel to each other. The algorithm developed provides a sliding window through the first vertical strip on the left side of the page. It runs through to identify the new minimum corresponding to a valley in the projection profile. Each valley would represent the starting point of the orientation line and the ending point is the minimum point on the projection profile of the next vertical strip. The derived text-lines traverse around any obstructing handwritten vertical strips of connected component by associating it to either the line above or below. A decision of associating such connected component is made by the probability obtained from a distance metric decision. The technique outperforms the global projection profile for text line segmentation and it is robust to handle skewed documents and those with lines running into each other.Keywords: connected-component, projection-profile, segmentation, text-line
Procedia PDF Downloads 1243216 Anti-lipidemic and Hematinic Potentials of Moringa Oleifera Leaves: A Clinical Trial on Type 2 Diabetic Subjects in a Rural Nigerian Community
Authors: Ifeoma C. Afiaenyi, Elizabeth K. Ngwu, Rufina N. B. Ayogu
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Diabetes has crept into the rural areas of Nigeria, causing devastating effects on its sufferers; most of them could not afford diabetic medications. Moringa oleifera has been used extensively in animal models to demonstrate its antilipidaemic and haematinic qualities; however, there is a scarcity of data on the effect of graded levels of Moringa oleifera leaves on the lipid profile and hematological parameters in human diabetic subjects. The study determined the effect of Moringa oleifera leaves on the lipid profile and hematological parameters of type 2 diabetic subjects in Ukehe, a rural Nigerian community. Twenty-four adult male and female diabetic subjects were purposively selected for the study. These subjects were shared into four groups of six subjects each. The diets used in the study were isocaloric. A control group (diabetics, group 1) was fed diets without Moringa oleifera leaves. Experimental groups 2, 3 and 4 received 20g, 40g and 60g of Moringa oleifera leaves daily, respectively, in addition to the diets. The subjects' lipid profile and hematological parameters were measured prior to the feeding trial and at the end of the feeding trial. The feeding trial lasted for fourteen days. The data obtained were analyzed using the computer program Statistical Product for Service Solution (SPSS) for windows version 21. A Paired-samples t-test was used to compare the means of values collected before and after the feeding trial within the groups and significance was accepted at p < 0.05. There was a non-significant (p > 0.05) decrease in the mean total cholesterol of the subjects in groups 1, 2 and 3 after the feeding trial. There was a non-significant (p > 0.05) decrease in the mean triglyceride levels of the subjects in group 1 after the feeding trial. Groups 1 and 3 subjects had a non-significant (p > 0.05) decrease in their mean low-density lipoprotein (LDL) cholesterol after the feeding trial. Groups 1, 2 and 4 had a significant (p < 0.05) increase in their mean high-density lipoprotein (HDL) cholesterol after the feeding trial. A significant (p < 0.05) decrease in the mean hemoglobin level was observed only in group 4 subjects. Similarly, there was a significant (p < 0.05) decrease in the mean packed cell volume of group 4 subjects. It was only in group 4 that a significant (p < 0.05) decrease in the mean white blood cells of the subjects was also observed. The changes observed in the parameters assessed were not dose-dependent. Therefore, a similar study of longer duration and more samples is imperative to authenticate these results.Keywords: anemia, diabetic subjects, lipid profile, moringa oleifera
Procedia PDF Downloads 2003215 Identification and Characterization of in Vivo, in Vitro and Reactive Metabolites of Zorifertinib Using Liquid Chromatography Lon Trap Mass Spectrometry
Authors: Adnan A. Kadi, Nasser S. Al-Shakliah, Haitham Al-Rabiah
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Zorifertinib is a novel, potent, oral, a small molecule used to treat non-small cell lung cancer (NSCLC). zorifertinib is an Epidermal Growth Factor Receptor (EGFR) inhibitor and has good blood–brain barrier permeability for (NSCLC) patients with EGFR mutations. zorifertinibis currently at phase II/III clinical trials. The current research reports the characterization and identification of in vitro, in vivo and reactive intermediates of zorifertinib. Prediction of susceptible sites of metabolism and reactivity pathways (cyanide and GSH) of zorifertinib were performed by the Xenosite web predictor tool. In-vitro metabolites of zorifertinib were performed by incubation with rat liver microsomes (RLMs) and isolated perfused rat liver hepatocytes. Extraction of zorifertinib and it's in vitro metabolites from the incubation mixtures were done by protein precipitation. In vivo metabolism was done by giving a single oral dose of zorifertinib(10 mg/Kg) to Sprague Dawely rats in metabolic cages by using oral gavage. Urine was gathered and filtered at specific time intervals (0, 6, 12, 18, 24, 48, 72,96and 120 hr) from zorifertinib dosing. A similar volume of ACN was added to each collected urine sample. Both layers (organic and aqueous) were injected into liquid chromatography ion trap mass spectrometry(LC-IT-MS) to detect vivozorifertinib metabolites. N-methyl piperizine ring and quinazoline group of zorifertinib undergoe metabolism forming iminium and electro deficient conjugated system respectively, which are very reactive toward nucleophilic macromolecules. Incubation of zorifertinib with RLMs in the presence of 1.0 mM KCN and 1.0 Mm glutathione were made to check reactive metabolites as it is often responsible for toxicities associated with this drug. For in vitro metabolites there were nine in vitro phase I metabolites, four in vitro phase II metabolites, eleven reactive metabolites(three cyano adducts, five GSH conjugates metabolites, and three methoxy metabolites of zorifertinib were detected by LC-IT-MS. For in vivo metabolites, there were eight in vivo phase I, tenin vivo phase II metabolitesofzorifertinib were detected by LC-IT-MS. In vitro and in vivo phase I metabolic pathways wereN- demthylation, O-demethylation, hydroxylation, reduction, defluorination, and dechlorination. In vivo phase II metabolic reaction was direct conjugation of zorifertinib with glucuronic acid and sulphate.Keywords: in vivo metabolites, in vitro metabolites, cyano adducts, GSH conjugate
Procedia PDF Downloads 1983214 Atypical Intoxication Due to Fluoxetine Abuse with Symptoms of Amnesia
Authors: Ayse Gul Bilen
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Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants that are used clinically for the treatment of anxiety disorders, obsessive-compulsive disorder (OCD), panic disorders and eating disorders. The first SSRI, fluoxetine (sold under the brand names Prozac and Sarafem among others), had an adverse effect profile better than any other available antidepressant when it was introduced because of its selectivity for serotonin receptors. They have been considered almost free of side effects and have become widely prescribed, however questions about the safety and tolerability of SSRIs have emerged with their continued use. Most SSRI side effects are dose-related and can be attributed to serotonergic effects such as nausea. Continuous use might trigger adverse effects such as hyponatremia, tremor, nausea, weight gain, sleep disturbance and sexual dysfunction. Moderate toxicity can be safely observed in the hospital for 24 hours, and mild cases can be safely discharged (if asymptomatic) from the emergency department once cleared by Psychiatry in cases of intentional overdose and after 6 to 8 hours of observation. Although fluoxetine is relatively safe in terms of overdose, it might still be cardiotoxic and inhibit platelet secretion, aggregation, and plug formation. There have been reported clinical cases of seizures, cardiac conduction abnormalities, and even fatalities associated with fluoxetine ingestions. While the medical literature strongly suggests that most fluoxetine overdoses are benign, emergency physicians need to remain cognizant that intentional, high-dose fluoxetine ingestions may induce seizures and can even be fatal due to cardiac arrhythmia. Our case is a 35-year old female patient who was sent to ER with symptoms of confusion, amnesia and loss of orientation for time and location after being found wandering in the streets unconsciously by police forces that informed 112. Upon laboratory examination, no pathological symptom was found except sinus tachycardia in the EKG and high levels of aspartate transaminase (AST) and alanine transaminase (ALT). Diffusion MRI and computed tomography (CT) of the brain all looked normal. Upon physical and sexual examination, no signs of abuse or trauma were found. Test results for narcotics, stimulants and alcohol were negative as well. There was a presence of dysrhythmia which required admission to the intensive care unit (ICU). The patient gained back her conscience after 24 hours. It was discovered from her story afterward that she had been using fluoxetine due to post-traumatic stress disorder (PTSD) for 6 months and that she had attempted suicide after taking 3 boxes of fluoxetine due to the loss of a parent. She was then transferred to the psychiatric clinic. Our study aims to highlight the need to consider toxicologic drug use, in particular, the abuse of selective serotonin reuptake inhibitors (SSRIs), which have been widely prescribed due to presumed safety and tolerability, for diagnosis of patients applying to the emergency room (ER).Keywords: abuse, amnesia, fluoxetine, intoxication, SSRI
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