Search results for: common drug combinations

Authors: Michio Kurosu

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Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

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Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

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

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

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Authors: Somayeh Akrami, Vali-Allah Mozaffarian, Habib Onsori

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The studied region in this research, watershed Kuhkamar river, is about 112.66 square kilometers, it is located between 45º 48' 9" to 45º 2' 20" N and 38º 34' 15" to 38º 40' 28" E. The gained results of the studies on flora combinations, proved 287 plant species in 190 genera and 51 families. Asteracea with 49 and Lamiaceae with 27 plant species are the major plant families. Among collected species one interesting plant was found and determined as a new record Anemone narcissiflora L. for flora of Iran. This plant is known as a complex species that shows intraspecific speciation and is classified into about 12 subspecies and 10 varieties in world. To identify the infraspecies taxons of this species, in addition to morphological characteristics, the use of appropriate molecular markers for the better isolation of the individuals were needed.

Keywords: Anemone narcissiflora, floristic Study, kuhkamar, molecular marker

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Authors: Tivani Phosa Mashamba-Thompson, Mahmoud E. S. Soliman

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To date, the cause of neurodegeneration is not well understood and diseases that stem from neurodegeneration currently have no known cures. Cathepsin B (CB) enzyme is known to be involved in the production of peptide neurotransmitters and toxic peptides in neurodegenerative diseases (NDs). CA-074Me is a membrane-permeable irreversible selective cathepsin B (CB) inhibitor as confirmed by in vivo studies. Due to the lack of the crystal structure, the binding mode of CA-074Me with the human CB at molecular level has not been previously reported. The main aim of this study is to gain an insight into the binding mode of CB CA-074Me to human CB using various computational tools. Herein, molecular dynamics simulations, binding free energy calculations and per-residue energy decomposition analysis were employed to accomplish the aim of the study. Another objective was to identify novel CB inhibitors based on the structure of CA-074Me using fragment based drug design using scaffold hoping drug design approach. Results showed that two of the designed ligands (hit 1 and hit 2) were found to have better binding affinities than the prototype inhibitor, CA-074Me, by ~2-3 kcal/mol. Per-residue energy decomposition showed that amino acid residues Cys29, Gly196, His197 and Val174 contributed the most towards the binding. The Van der Waals binding forces were found to be the major component of the binding interactions. The findings of this study should assist medicinal chemist towards the design of potential irreversible CB inhibitors.

Keywords: cathepsin B, scaffold hopping, docking, molecular dynamics, binding-free energy, neurodegerative diseases

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Authors: Jignasha Derasari, Patel Krishna M, Modi Jignasa G.

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Chemical stability of pharmaceutical molecules is a matter of great concern as it affects the safety and efficacy of the drug product.Stability testing data provides the basis to understand how the quality of a drug substance and drug product changes with time under the influence of various environmental factors. Besides this, it also helps in selecting proper formulation and package as well as providing proper storage conditions and shelf life, which is essential for regulatory documentation. The ICH guideline states that stress testing is intended to identify the likely degradation products which further help in determination of the intrinsic stability of the molecule and establishing degradation pathways, and to validate the stability indicating procedures. A simple, accurate and precise stability indicating RP- HPLC method was developed and validated for simultaneous estimation of Amiloride Hydrochloride and Furosemide in tablet dosage form. Separation was achieved on an Phenomenexluna ODS C18 (250 mm × 4.6 mm i.d., 5 µm particle size) by using a mobile phase consisting of Ortho phosphoric acid: Acetonitrile (50:50 %v/v) at a flow rate of 1.0 ml/min (pH 3.5 adjusted with 0.1 % TEA in Water) isocratic pump mode, Injection volume 20 µl and wavelength of detection was kept at 283 nm. Retention time for Amiloride Hydrochloride and Furosemide was 1.810 min and 4.269 min respectively. Linearity of the proposed method was obtained in the range of 40-60 µg/ml and 320-480 µg/ml and Correlation coefficient was 0.999 and 0.998 for Amiloride hydrochloride and Furosemide, respectively. Forced degradation study was carried out on combined dosage form with various stress conditions like hydrolysis (acid and base hydrolysis), oxidative and thermal conditions as per ICH guideline Q2 (R1). The RP- HPLC method has shown an adequate separation for Amiloride hydrochloride and Furosemide from its degradation products. Proposed method was validated as per ICH guidelines for specificity, linearity, accuracy; precision and robustness for estimation of Amiloride hydrochloride and Furosemide in commercially available tablet dosage form and results were found to be satisfactory and significant. The developed and validated stability indicating RP-HPLC method can be used successfully for marketed formulations. Forced degradation studies help in generating degradants in much shorter span of time, mostly a few weeks can be used to develop the stability indicating method which can be applied later for the analysis of samples generated from accelerated and long term stability studies. Further, kinetic study was also performed for different forced degradation parameters of the same combination, which help in determining order of reaction.

Keywords: amiloride hydrochloride, furosemide, kinetic study, stability indicating RP-HPLC method validation

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Authors: Pablo J. Valverde, Jaime E. Fernandez

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This paper shows under which conditions public corruption can emerge. The theoretical model includes variables such as the public employee wage (w), a control corruption parameter (c), and the group size of interactions (GS) between clusters of public officers and contractors. The system behavior is analyzed using phase diagrams based on combinations of such parameters (c, w, GS). Numerical simulations are implemented in order to contrast analytic results based on Nash equilibria of the theoretical model. Major findings include the functional relationship between wages and network topology, which attempts to reduce the emergence of corrupt behavior.

Keywords: public corruption, game theory, complex systems, Nash equilibrium.

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Authors: Cruz Queen Allysa Rose, Bautista Joymeeh Anne, Lantoria Kaye, Barretto Katya Louise

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The study presents the preferences of passengers on the quality of service provided by the two airline check-in methods currently present in airports-traditional counter check-in and common-use self-service kiosks. Since a study has shown that airlines perceive self-service kiosks alone are sufficient enough to ensure adequate services and customer satisfaction, and in contrast, agents and passengers stated that it alone is not enough and that human interaction is essential. In reference with former studies that established opposing ideas about the choice of the more favorable airline check-in method to employ, it is the purpose of this study to present a recommendation that shall somehow fill-in the gap between the conflicting ideas by means of comparing the perceived quality of service through the RATER model. Furthermore, this study discusses the major competencies present in each method which are supported by the theories–FIRO Theory of Needs upholding the importance of inclusion, control and affection, and the Queueing Theory which points out the discipline of passengers and the length of the queue line as important factors affecting quality service. The findings of the study were based on the data gathered by the researchers from selected Thomasian third year and fourth year college students currently enrolled in the first semester of the academic year 2014-2015, who have already experienced both airline check-in methods through the implication of a stratified probability sampling. The statistical treatments applied in order to interpret the data were mean, frequency, standard deviation, t-test, logistic regression and chi-square test. The final point of the study revealed that there is a greater effect in passenger preference concerning the satisfaction experienced in common-use self-service kiosks in comparison with the application of the traditional counter check-in.

Keywords: traditional counter check-in, common-use self-service Kiosks, airline check-in methods

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Authors: Wenfu Zheng, Guanghe Zheng

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The discussion on the social sustainability in existing literature is limited to two-dimension epistemology space with only two elements: the human and nature. Using the revelation of the Bible God, the paper adds a moral component to the two-dimension space. With the new variable being introduced, the authors formulate a to three-dimension epistemology space and discuss its implications. Based on the space, the authors explore the hierarchical structure of order principles for a sustainable society. The social order principle system hierarchically consists of three principles: moral, relational, and rational. The justification of every principle is analyzed briefly. The paper concluded that all these order principles are necessary assurance of building a sustainable society.

Keywords: common grace, saving grace, sustainable society, the image of God

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Authors: M. Aboalazayem, Essam A. Gouda, Ahmed M. Moussa, Amr E. Flifl

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Field data collecting is considered one of the most difficult work due to the difficulty of accessing large zones such as large lakes. Also, it is well known that the cost of obtaining field data is very expensive. Remotely monitoring of lake water quality (WQ) provides an economically feasible approach comparing to field data collection. Researchers have shown that lake WQ can be properly monitored via Remote sensing (RS) analyses. Using satellite images as a method of WQ detection provides a realistic technique to measure quality parameters across huge areas. Landsat (LS) data provides full free access to often occurring and repeating satellite photos. This enables researchers to undertake large-scale temporal comparisons of parameters related to lake WQ. Satellite measurements have been extensively utilized to develop algorithms for predicting critical water quality parameters (WQPs). The goal of this paper is to use RS to derive WQ indicators in Aswan High Dam Reservoir (AHDR), which is considered Egypt's primary and strategic reservoir of freshwater. This study focuses on using Landsat8 (L-8) band surface reflectance (SR) observations to predict water-quality characteristics which are limited to Turbidity (TUR), total suspended solids (TSS), and chlorophyll-a (Chl-a). ArcGIS pro is used to retrieve L-8 SR data for the study region. Multiple linear regression analysis was used to derive new correlations between observed optical water-quality indicators in April and L-8 SR which were atmospherically corrected by values of various bands, band ratios, and or combinations. Field measurements taken in the month of May were used to validate WQP obtained from SR data of L-8 Operational Land Imager (OLI) satellite. The findings demonstrate a strong correlation between indicators of WQ and L-8 .For TUR, the best validation correlation with OLI SR bands blue, green, and red, were derived with high values of Coefficient of correlation (R2) and Root Mean Square Error (RMSE) equal 0.96 and 3.1 NTU, respectively. For TSS, Two equations were strongly correlated and verified with band ratios and combinations. A logarithm of the ratio of blue and green SR was determined to be the best performing model with values of R2 and RMSE equal to 0.9861 and 1.84 mg/l, respectively. For Chl-a, eight methods were presented for calculating its value within the study area. A mix of blue, red, shortwave infrared 1(SWR1) and panchromatic SR yielded the greatest validation results with values of R2 and RMSE equal 0.98 and 1.4 mg/l, respectively.

Keywords: remote sensing, landsat 8, nasser lake, water quality

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Authors: Amir Reza Heydari, Yaser Jenab

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Coronary artery disease, a common cardiovascular disease, is attributed to the accumulation of cholesterol-based plaques in the coronary arteries, leading to atherosclerosis. This disease is associated with risk factors such as smoking, hypertension, diabetes, and elevated cholesterol levels, contributing to severe clinical consequences, including acute coronary syndromes and myocardial infarction. Treatment approaches such as from lifestyle interventions to surgical procedures like percutaneous coronary intervention and coronary artery bypass surgery. These interventions often employ stents, including bare-metal stents (BMS), drug-eluting stents (DES), and bioresorbable vascular scaffolds (BVS), each with its advantages and limitations. Computational tools have emerged as critical in optimizing stent designs and assessing their performance. The aim of this study is to provide an overview of the computational methods of studies based on the finite element (FE) method in the field of coronary stenting and discuss the potential for development and clinical application of stent devices. Additionally, the importance of assessing the ability of computational models is emphasized to represent real-world phenomena, supported by recent guidelines from the American Society of Mechanical Engineers (ASME). Validation processes proposed include comparing model performance with in vivo, ex-vivo, or in vitro data, alongside uncertainty quantification and sensitivity analysis. These methods can enhance the credibility and reliability of in silico simulations, ultimately aiding in the assessment of coronary stent designs in various clinical contexts.

Keywords: atherosclerosis, materials, restenosis, review, validation

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Authors: Anteneh Getachew Gebrie, Rabian Wangkeeree

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The purpose of this paper is to introduce iterative algorithm solving split system of minimization problem given as a task of finding a common minimizer point of finite family of proper, lower semicontinuous convex functions and whose image under a bounded linear operator is also common minimizer point of another finite family of proper, lower semicontinuous convex functions. We obtain strong convergence of the sequence generated by our algorithm under some suitable conditions on the parameters. The iterative schemes are developed with a way of selecting the step sizes such that the information of operator norm is not necessary. Some applications and numerical experiment is given to analyse the efficiency of our algorithm.

Keywords: Hilbert Space, minimization problems, Moreau-Yosida approximate, split feasibility problem

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Authors: Ming Luo

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In this real world, a manufacturer may produce more than one product. The products produced by the same manufacturer may share the same type of parts, similar design, and be produced in the same factory, i.e. some common causes. From the perspective of warranty management, the frequencies of those products’ warranty claims may have statistical dependence caused by the common causes. Warranty policy optimisation in the existing research, majorly, has not considered such dependence, which may increase bias in decision making. In the market, renewing warranty policies are provided to some unrepairable products and consumer electronic products. This paper optimises the renewing warranty policy collectively in a multi-product scenario with a consideration of the dependence among the warranty claims of the products produced by the same manufacturer. The existence of the optimal solution is proved. Numerical examples are used to validate the applicability of the proposed methods.

Keywords: mean-risk framework, modern portfolio theory, renewing warranty policy, warranty policy optimisation

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Authors: Vanessa Kummer, Maik Meusel

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Real estate demand estimates are typically derived from transaction data. However, in regions with excess demand, transactions are driven by supply and therefore do not indicate what people are actually looking for. To estimate the demand for housing in Switzerland, search subscriptions from all important Swiss real estate platforms are used. These data do, however, suffer from missing information—for example, many users do not specify how many rooms they would like or what price they would be willing to pay. In economic analyses, it is often the case that only complete data is used. Usually, however, the proportion of complete data is rather small which leads to most information being neglected. Also, the data might have a strong distortion if it is complete. In addition, the reason that data is missing might itself also contain information, which is however ignored with that approach. An interesting issue is, therefore, if for economic analyses such as the one at hand, there is an added value by using the whole data set with the imputed missing values compared to using the usually small percentage of complete data (baseline). Also, it is interesting to see how different algorithms affect that result. The imputation of the missing data is done using unsupervised learning. Out of the numerous unsupervised learning approaches, the most common ones, such as clustering, principal component analysis, or neural networks techniques are applied. By training the model iteratively on the imputed data and, thereby, including the information of all data into the model, the distortion of the first training set—the complete data—vanishes. In a next step, the performances of the algorithms are measured. This is done by randomly creating missing values in subsets of the data, estimating those values with the relevant algorithms and several parameter combinations, and comparing the estimates to the actual data. After having found the optimal parameter set for each algorithm, the missing values are being imputed. Using the resulting data sets, the next step is to estimate the willingness to pay for real estate. This is done by fitting price distributions for real estate properties with certain characteristics, such as the region or the number of rooms. Based on these distributions, survival functions are computed to obtain the functional relationship between characteristics and selling probabilities. Comparing the survival functions shows that estimates which are based on imputed data sets do not differ significantly from each other; however, the demand estimate that is derived from the baseline data does. This indicates that the baseline data set does not include all available information and is therefore not representative for the entire sample. Also, demand estimates derived from the whole data set are much more accurate than the baseline estimation. Thus, in order to obtain optimal results, it is important to make use of all available data, even though it involves additional procedures such as data imputation.

Keywords: demand estimate, missing-data imputation, real estate, unsupervised learning

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Authors: Ioana Pisica, Dimitrios Gkritzapis

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The significance of UAS in scientific applications has been amply demonstrated in recent years. The combinations of portability and quasi-static positioning by means of flying in close loop path make them versatile and efficient in the inspection of power systems infrastructure. In this paper, we critically assess several platforms and sensor capabilities to identify their pros and cons in relation to the power systems assets to be monitored. In this respect, it is paramount the flights to be conducted by using UAS which bear certain suitable features, such as responsive and easy control, video capturing in real time, autonomous routing of pre-planned flight programming with differentiating payloads. The outcome of this research is a set of optimal requirements for power system assets monitoring with UAS.

Keywords: platforms, power system, sensors, UAVs

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Authors: Karolis Leonavičius, Dalius Kučiauskas, Dangiras Lukošius, Arnoldas Jasiūnas, Kostas Zdanys, Rokas Stanislovas, Emilis Gegevičius, Žana Kapustina, Juozas Nainys

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Screening throughput is a common bottleneck in many research areas, including functional genomics, drug discovery, and directed evolution. High-throughput screening techniques can be classified into two main categories: (i) affinity-based screening and (ii) functional screening. The first one relies on binding assays that provide information about the affinity of a test molecule for a target binding site. Binding assays are relatively easy to establish; however, they reveal no functional activity. In contrast, functional assays show an effect triggered by the interaction of a ligand at a target binding site. Functional assays might be based on a broad range of readouts, such as cell proliferation, reporter gene expression, downstream signaling, and other effects that are a consequence of ligand binding. Screening of large cell or gene libraries based on direct activity rather than binding affinity is now a preferred strategy in many areas of research as functional assays more closely resemble the context where entities of interest are anticipated to act. Droplet sorting is the basis of high-throughput functional biological screening, yet its applicability is limited due to the technical complexity of integrating high-performance droplet analysis and manipulation systems. As a solution, the Droplet Genomics Styx platform enables custom droplet sorting workflows, which are necessary for the development of early-stage or complex biological therapeutics or industrially important biocatalysts. The poster will focus on the technical design considerations of Styx in the context of its application spectra.

Keywords: functional screening, droplet microfluidics, droplet sorting, dielectrophoresis

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Authors: M. Khalid, G. N. Singh

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In this paper, we have considered the problem of estimation for population mean, on current (second) occasion in the presence of random non response in two-occasion successive sampling under two phase set-up. Modified exponential type estimators have been proposed, and their properties are studied under the assumptions that numbers of sampling units follow a distribution due to random non response situations. The performances of the proposed estimators are compared with linear combinations of two estimators, (a) sample mean estimator for fresh sample and (b) ratio estimator for matched sample under the complete response situations. Results are demonstrated through empirical studies which present the effectiveness of the proposed estimators. Suitable recommendations have been made to the survey practitioners.

Keywords: successive sampling, random non-response, auxiliary variable, bias, mean square error

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

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

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

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Authors: Shehroz Mukhtar, Maqsood Ahmed, Abdullah Mukhtar, Choudhry Shahid, Waqar Javaid

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Code switching is a common phenomenon, generally observed in multilingual communities across the globe. A critical look at code switching literature reveals that mostly code switching has been studied in classroom in learning and teaching context while code switching outside classroom in settings such as café, hostel and so on have been the least explored areas. Current research investigated the reasons for code switching in the interactive practices of students and their perceptions regarding the same outside the classroom settings. This paper is the study of the common practice that prevails in the Universities of Sialkot that bilinguals mix two languages when they speak in different class room situations. In Pakistani classrooms where Multilingual are in abundance i.e. they can speak two or more than two languages at the same time, the code switching or language combination is very common. The teachers of Sialkot switch from one language to another consciously or unconsciously while teaching English in the class rooms. This phenomenon has not been explored in the Sialkot’s teaching context. In Sialkot private educational institutes does not encourage code-switching whereas the public or government institutes use it frequently. The crux of this research is to investigate and identify the importance of code switching by taking its users in consideration. Survey research method and survey questionnaire will be used to get exact data from teachers and students. We will try to highlight the functions and importance of code switching in foreign language classrooms of Sialkot and will explore why this trend is emerging in Sialkot.

Keywords: code switching, bilingual context, L1, L2

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Authors: Anupalli Roja Rani, Pavithra Dasari

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Background: Among several, breast cancer has emerged as the most common female cancer in developing countries. It is the most common cause of cancer-related deaths worldwide among women. It is a molecularly and clinically heterogeneous disease. Moreover, it is a hormone–dependent tumor in which estrogens can regulate the growth of breast cells by binding with estrogen receptors (ERs). Moreover, the use of natural products in cancer therapeutics is due to their properties of biocompatibility and less toxicity. Plants are the vast reservoirs for various bioactive compounds. Coleus barbatus (Lamiaceae) contains anticancer properties against several cancer cell lines. Method: In the present study, an attempt is being made to enrich the knowledge of the anticancer activity of pure compounds extracted from Coleus barbatus (Andrew). On human breast cancer cell lines MCF-7. Here in, we are assessing the antiproliferative activity of Coleus barbatus (Andrew) plant extracts against MCF 7 and also evaluating their toxicity in normal human mammary cell lines such as Human Mammary Epithelial Cells (HMEC). The active fraction of plant extract was further purified with the help of Flash chromatography, Medium Pressure Liquid Chromatography (MPLC) and preparative High-Performance Liquid Chromatography (HPLC). The structure of pure compounds will be elucidated by using modern spectroscopic methods like Nuclear magnetic resonance (NMR), Electrospray Ionisation Mass Spectrometry (ESI-MS) methods. Later, the growth inhibition morphological assessment of cancer cells and cell cycle analysis of purified compounds were assessed using FACS. The growth and progression of signaling molecules HER2, GRP78 was studied by secretion assay using ELISA and expression analysis by flow cytometry. Result: Cytotoxic effect against MCF-7 with IC50 values were derived from dose response curves, using six concentrations of twofold serially diluted samples, by SOFTMax Pro software (Molecular device) and respectively Ellipticine and 0.5% DMSO were used as a positive and negative control. Conclusion: The present study shows the significance of various bioactive compounds extracted from Coleus barbatus (Andrew) root material. It acts as an anti-proliferative and shows cytotoxic effects on human breast cancer cell lines MCF7. The plant extracts play an important role pharmacologically. The whole plant has been used in traditional medicine for decades and the studies done have authenticated the practice. Earlier, as described, the plant has been used in the ayurveda and homeopathy medicine. However, more clinical and pathological studies must be conducted to investigate the unexploited potential of the plant. These studies will be very useful for drug designing in the future.

Keywords: coleus barbatus, HPLC, MPLC, NMR, MCF7, flash chromatograph, ESI-MS, FACS, ELISA.

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Authors: Parthiban Srinivasan

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With recent advances in computational power and access to enough data in biosciences, artificial intelligence methods are increasingly being used in drug discovery research. These methods are essentially a series of advanced statistics based exercises that review the past to indicate the likely future. Our goal is to develop a model that accurately predicts biological activity and toxicity parameters for novel compounds. We have compiled a robust library of over 150,000 chemical compounds with different pharmacological properties from literature and public domain databases. The compounds are stored in simplified molecular-input line-entry system (SMILES), a commonly used text encoding for organic molecules. We utilize an automated process to generate an array of numerical descriptors (features) for each molecule. Redundant and irrelevant descriptors are eliminated iteratively. Our prediction engine is based on a portfolio of machine learning algorithms. We found Random Forest algorithm to be a better choice for this analysis. We captured non-linear relationship in the data and formed a prediction model with reasonable accuracy by averaging across a large number of randomized decision trees. Our next step is to apply deep neural network (DNN) algorithm to predict the biological activity and toxicity properties. We expect the DNN algorithm to give better results and improve the accuracy of the prediction. This presentation will review all these prominent machine learning and deep learning methods, our implementation protocols and discuss these techniques for their usefulness in biomedical and health informatics.

Keywords: deep learning, drug discovery, health informatics, machine learning, toxicity prediction

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Authors: Ramandeep Kaur, Makula Ajitha

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Fluvastatin has been reported for increasing bone mineral density in osteoporosis since last decade. Systemically administered drug undergoes extensive hepatic first-pass metabolism, thus very small amount of drug reaches the bone tissue which is highly insignificant. The present study aims to deliver fluvastatin in the form of nanoemulsion (NE) gel directly to the bone tissue through transdermal route thereby bypassing hepatic first pass metabolism. The NE formulation consisted of isopropyl myristate as oil, tween 80 as surfactant, transcutol as co-surfactant and water as the aqueous phase. Pseudoternary phase diagrams were constructed using aqueous titration method and NE’s obtained were subjected to thermodynamic-kinetic stability studies. The stable NE formulations were evaluated for their droplet size, zeta potential, and transmission electron microscopy (TEM). The nano-sized formulations were incorporated into 0.5% carbopol 934 gel matrix. Ex-vivo permeation behaviour of selected formulations through rat skin was investigated and compared with the conventional formulations (suspension and emulsion). Further, in-vivo pharmacokinetic study was carried using male Wistar rats. The optimized NE formulations mean droplet size was 11.66±3.2 nm with polydispersity index of 0.117. Permeation flux of NE gel formulations was found significantly higher than the conventional formulations i.e. suspension and emulsion. In vivo pharmacokinetic study showed significant increase in bioavailability (1.25 fold) of fluvastatin than oral formulation. Thus, it can be concluded that NE gel was successfully developed for transdermal delivery of fluvastatin for the treatment of osteoporosis.

Keywords: fluvastatin, nanoemulsion gel, osteoporosis, transdermal

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Authors: Anthony S. Machi, Joseph Minardi

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We present a case report of left atrial myxoma diagnosed by bedside transesophageal (TEE) ultrasound. Left atrial myxoma is the most common benign cardiac tumor and can obstruct blood flow and cause valvular insufficiency. Common symptoms consist of dyspnea, pulmonary edema and other features of left heart failure in addition to thrombus release in the form of tumor fragments. The availability of bedside ultrasound equipment is essential for the quick diagnosis and treatment of various emergency conditions including cardiac neoplasms. A 48-year-old Caucasian female with a four-year history of an untreated renal mass and anemia presented to the ED with two months of sharp, intermittent, bilateral flank pain radiating into the abdomen. She also reported intermittent vomiting and constipation along with generalized body aches, night sweats, and 100-pound weight loss over last year. She had a CT in 2013 showing a 3 cm left renal mass and a second CT in April 2016 showing a 3.8 cm left renal mass along with a past medical history of diverticulosis, chronic bronchitis, dyspnea on exertion, uncontrolled hypertension, and hyperlipidemia. Her maternal family history is positive for breast cancer, hypertension, and Type II Diabetes. Her paternal family history is positive for stroke. She was a current everyday smoker with an 11 pack/year history. Alcohol and drug use were denied. Physical exam was notable for a Grade II/IV systolic murmur at the right upper sternal border, dyspnea on exertion without angina, and a tender left lower quadrant. Her vitals and labs were notable for a blood pressure of 144/96, heart rate of 96 beats per minute, pulse oximetry of 96%, hemoglobin of 7.6 g/dL, hypokalemia, hypochloremia, and multiple other abnormalities. Physicians ordered a CT to evaluate her flank pain which revealed a 7.2 x 8.9 x 10.5 cm mixed cystic/solid mass in the lower pole of the left kidney and a filling defect in the left atrium. Bedside TEE was ordered to follow up on the filling defect. TEE reported an ejection fraction of 60-65% and visualized a mobile 6 x 3 cm mass in the left atrium attached to the interatrial septum extending into the mitral valve. Cardiothoracic Surgery and Urology were consulted and confirmed a diagnosis of left atrial myxoma and clear cell renal cell carcinoma. The patient returned a week later due to worsening nausea and vomiting and underwent emergent nephrectomy, lymph node dissection, and colostomy due to a necrotic colon. Her condition declined over the next four months due to lung and brain metastases, infections, and other complications until she passed away.

Keywords: bedside ultrasound, echocardiography, emergency medicine, left atrial myxoma

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Authors: M.R Asghari Bejestani, Gh. R. Mohammad Khani, V.R. Nafisi

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Imagined speech recognition is one of the most interesting approaches to BCI development and a lot of works have been done in this area. Many different experiments have been designed and hundreds of combinations of feature extraction methods and classifiers have been examined. Reported classification accuracies range from the chance level to more than 90%. Based on non-stationary nature of brain signals, we have introduced 3 classification modes according to time difference in inter and intra-class samples. The modes can explain the diversity of reported results and predict the range of expected classification accuracies from the brain signal accusation procedure. In this paper, a few samples are illustrated by inspecting results of some previous works.

Keywords: brain computer interface, silent talk, imagined speech, classification, signal processing

Procedia PDF Downloads 140

Authors: Shehroz Mukhtar, Maqsood Ahmed, Abdullah Mukhtar, Choudhry Shahid, Waqar Javaid

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Code switching is a common phenomenon, generally observed in multilingual communities across the globe. A critical look at code-switching literature reveals that mostly code-switching has been studied in the classrooms in learning and teaching contexts, while code-switching outside the classroom in settings such as café, hostels and so on has been the least explored areas. The current research investigated the reasons for code-switching in the interactive practices of students and their perceptions regarding the same outside the classroom settings. This paper is the study of the common practice that prevails in the Universities of Sialkot that bilinguals mix two languages when they speak in different classroom situations. In Pakistani classrooms where Multilingual is in abundance, i.e. they can speak two or more two languages at the same time, code-switching or language combination is very common. The teachers of Sialkot switch from one language to another consciously or unconsciously while teaching English in the classrooms. This phenomenon has not been explored in Sialkot’s teaching context. In Sialkot, private educational institutes do not encourage code-switching, whereas public or government institutes use it frequently. The crux of this research is to investigate and identify the importance of code-switching by taking its users into consideration. The survey research method and survey questionnaire will be used to get exact data from teachers and students. We will try to highlight the functions and importance of code switching in foreign language classrooms of Sialkot and will explore why this trend is emerging in Sialkot.

Keywords: code switching, foreign language classrooms, bilingual context, use of L1, importance of L2.

Procedia PDF Downloads 46

Authors: Hasan Aydogan

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The changes in the performance, emission and combustion characteristics of bioethanol-safflower biodiesel and diesel fuel blends used in a common rail diesel engine were investigated in this experimental study. E20B20D60 (20% bioethanol, 20% biodiesel, 60% diesel fuel by volume), E30B20D50, E50B20D30 and diesel fuel (D) were used as fuel. The tests were performed at full throttle valve opening and variable engine speeds. The results of the tests showed decreases in engine power, engine torque, carbon monoxide (CO), hydrocarbon (HC) and smoke density values with the use of bioethanol-biodiesel and diesel fuel blends, whereas, increases were observed in nitrogen oxide (NOx) and brake specific fuel consumption (BSFC) values. When combustion characteristics were examined, it was seen that the values were close to one another.

Keywords: bioethanol, biodiesel, safflower, combustion characteristics

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Authors: Famurewa Olumide Joseph, Akinsulore Adesanmi

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The current study investigated aggressive behaviour and its association with substance use disorder among senior secondary school students in Ilesha, Nigeria. Participants were three hundred and seventy-five (375) comprising (212) females and (163) males of senior secondary school students in Ilesa East and Ilesa West; who were randomly selected among the population of students from the schools. The mean age of the respondents was 14.61 years (S.D = 1.16), with 311 (82.9%) between 14 – 16 years. Female respondents were 212 (56.5%), while male respondents were 163 (43.5%). A cross sectional design was adopted. Three instruments were used for data collection. Buss Perry Aggression Questionnaire, Alcohol Use Disorder Identification Test (AUDIT) and Drug Abuse Screening Test (DAST). It was hypothesized that aggressive behaviour will be associated with substance use disorder among senior secondary school students in Ilesa East and Ilesa West. The result indicated that the overall prevalence of substance use disorder was 16.0%. Chi-Square test exploring the association between aggressive behaviour and substance use disorder shows that there is a significant association between aggressive behaviour and substance use disorder (χ2 =8.55, p =0.014). Results also showed that emotional problem (χ2 (2) =13.0; p = 0.001) was statistically significant while current medications intake (χ2 (2) =2.03; p =0.362) and overall wellbeing (χ2 (4) =2.49; p =0.646) were not statistically significant. There is an inverse association between prosocial behaviour and aggressive behaviour (r= -0.037, p>0.05). This indicates that as the level of prosocial behaviour increases, the level of aggressive behaviour among respondents decreases. However, alcohol use had no correlation with aggressive behaviour (r=0.070, p>0.05). Among the implications stated is that factors such as emotional symptoms, conduct problems, hyperactivity, peer problem and drug use contributed to the prevalence of aggressive behaviour among students. Suggestions for further studies were equally made.

Keywords: aggressive behaviour, alcohol, prevalence, students, substance use disorder (SUD)

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Authors: Habib Noorbhai

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This study primarily aimed to investigate the batting backlift technique (BBT) among semi-professional, professional and current international cricket players. A key question was to investigate if the lateral batting backlift technique (LBBT) is more common at the highest levels of the game. The participants in this study sample (n = 130) were South African semi-professional players (SP) (n = 69) and professional players (P) (n = 49) and South African international professional players (SAI) (n = 12). Biomechanical and video analysis were performed on all participant groups. Classifiers were utilised to identify the batting backlift technique type (BBTT) employed by all batsmen. All statistics and wagon wheels (scoring areas of the batsmen on a cricket field) were sourced online. This study found that a LBBT is more common at the highest levels of cricket batsmanship with batsmen at the various levels of cricket having percentages of the LBBT as follows: SP = 37.7%; P = 38.8%; SAI = 75%; p = 0.001. This study also found that SAI batsmen who used the LBBT were more proficient at scoring runs in various areas around the cricket field (according to the wagon wheel analysis). This study found that a LBBT is more common at the highest levels of cricket batsmanship. Cricket coaches should also pay attention to the direction of the backlift with players, especially when correlating the backlift to various scoring areas on the cricket field. Further in-depth research is required to fully investigate the change in batting backlift techniques among cricket players over a long-term period.

Keywords: cricket batting, biomechanical analysis, backlift, performance

Procedia PDF Downloads 255

Authors: Nancy M. El-Baz, Laila Ziko, Rania Siam, Wael Mamdouh

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Cancer is one of the most devastating diseases, and has over than 10 million new cases annually worldwide. Despite the effectiveness of chemotherapeutic agents, their systemic toxicity and non-selective anticancer actions represent the main obstacles facing cancer curability. Due to the effective enhanced permeability and retention (EPR) effect of nanomaterials, nanoparticles (NPs) have been used as drug nanocarriers providing targeted cancer drug delivery systems. In addition, several inorganic nanoparticles such as silver (AgNPs) nanoparticles demonstrated a potent anticancer activity against different cancers. The present study aimed at formulating core-shell inorganic NPs-based combinatorial therapy based on combining the anticancer activity of AgNPs along with doxorubicin (DOX) and evaluating their cytotoxicity on MCF-7 breast cancer cells. These inorganic NPs-based combinatorial therapies were designed to (i) Target and kill cancer cells with high selectivity, (ii) Have an improved efficacy/toxicity balance, and (iii) Have an enhanced therapeutic index when compared to the original non-modified DOX with much lower dosage The in-vitro cytotoxicity studies demonstrated that the NPs-based combinatorial therapy achieved the same efficacy of non-modified DOX on breast cancer cell line, but with 96% reduced dose. Such reduction in DOX dose revealed that the combination between DOX and NPs possess a synergic anticancer activity against breast cancer. We believe that this is the first report on a synergic anticancer effect at very low dose of DOX against MCF-7 cells. Future studies on NPs-based combinatorial therapy may aid in formulating novel and significantly more effective cancer therapeutics.

Keywords: nanoparticles-based combinatorial therapy, silver nanoparticles, doxorubicin, breast cancer

Procedia PDF Downloads 424

Authors: Milijana N. Miljkovic, Viktorija M. Dragojevic-Simic, Nemanja K. Rancic, Vesna M. Jacevic, Snezana B. Djordjevic, Momir M. Mikov, Aleksandra M. Kovacevic

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Itraconazole (ITZ) is a weak base and extremely lipophilic compound, with water solubility as a rate-limiting step in its absorption from the gastrointestinal tract. Its absolute bioavailability, about 55%, is maximal when its oral formulation, capsules, are taken immediately after a full meal. Peak plasma concentrations (Cmax) are reached within 2 to 5 hrs after their administration. ITZ undergoes extensive hepatic metabolism by human CYP3A4 isoenzyme and more than 30 different metabolites have been identified. One of the main ones is hydroxyitraconazole (HITZ), in which plasma concentrations are almost twice higher than those of ITZ. Gender differences in drug PK (Pharmacokinetics) have already been recognized, but variations in metabolism are believed to be their major cause. The aim of the study was to investigate the influence of gender on ITZ PK parameters after administration of oral capsule formulation, following 100 mg single dosing in healthy adult volunteers under fed conditions. The single-center, open-label PK study was performed. PK analyses included PK parameters obtained after a single 100 mg dose administration of itraconazole capsules to 48 females and 66 males. Blood samples were collected at pre-dose and up to 72.0 h after administration (1.0, 2.0, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0, 9.0, 12.0, 24.0, 36.0 and 72.0 hrs). The calculated pharmacokinetic parameters, based on the plasma concentrations of itraconazole and hydroxyitraconazole, were Cmax, AUClast, and AUCtot. Plasma concentrations of ITZ and HITZ were determined using a validated liquid chromatographic method with mass spectrometric detection, while pharmacokinetic parameters were estimated using non-compartmental methods. The pharmacokinetic analyses were performed using Kinetica software version 5.0. The mean value of ITZ Cmaxmen was 74.79 ng/ml, and Cmaxwomen was 51.291 ng/ml (independent samples test; p = 0.005). Hydroxyitraconazole had a mean value of Cmaxmen 106.37 ng/ml, and the mean value Cmaxwomen was 70.05 ng/ml. Women had, on average, lower AUClast and Cmax than men. AUClastmen for ITZ was 736.02 ng/mL*h and AUClastwomen was 566.62 ng/mL*h, while AUClastmen for HITZ was 1154.80 was ng/mL*h and AUClastwomen for HITZ was 708.12 ng/mL*h (independent samples test; p = 0.033). The mean values of ITZ AUCtotmen were 884.73 ng/mL*h and AUCtotwomen was 685.10 ng/mL*h. AUCtotmen for HITZ was 1290.41 ng/mL*h, while AUCtotwomen for HIZT was 788.60 ng/mL*h (p < 0.001). The results could point out to lower oral bioavailability of ITZ in women, since values of Cmax, AUClast, and AUCtot of both ITZ and HITZ were significantly lower in women than in men, respectively. The reason may be higher expression and activity of CYP3A4 in women than in men, but there also may be differences in other PK parameters. High variability of both ITZ and HITZ concentrations in both genders confirmed that ITZ is a highly variable drug. Further examinations of its PK are needed to justify strategies for therapeutic drug monitoring in patients treated by this antifungal agent.

Keywords: itraconazole, gender, hydroxyitraconazole, pharmacokinetics

Procedia PDF Downloads 129

Authors: Mostafa Mabrouk, Basma E. Abdel-Ghany, Mona Moaness, Bothaina M. Abdel-Hady, Hanan H. Beherei

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Tissue engineering became a promising field for bone repair and regenerative medicine in which cultured cells, scaffolds and osteogenic inductive signals are used to regenerate tissues. The annual cost of treating bone defects in Egypt has been estimated to be many billions, while enormous costs are spent on imported bone grafts for bone injuries, tumors, and other pathologies associated with defective fracture healing. The current study is aimed at developing a more strategic approach in order to speed-up recovery after bone damage. This will reduce the risk of fatal surgical complications and improve the quality of life of people affected with such fractures. 3D scaffolds loaded with cheap nano-particles that possess an osteogenic effect were prepared by nano-electrospinning. The Microstructure and morphology characterizations of the 3D scaffolds were monitored using scanning electron microscopy (SEM). The physicochemical characterization was investigated using X-ray diffractometry (XRD) and infrared spectroscopy (IR). The Physicomechanical properties of the 3D scaffold were determined by a universal testing machine. The in vitro bioactivity of the 3D scaffold was assessed in simulated body fluid (SBF). The bone-bonding ability of novel 3D scaffolds was also evaluated. The obtained nanofibrous scaffolds demonstrated promising microstructure, physicochemical and physicomechanical features appropriate for enhanced bone regeneration. Therefore, the utilized nanomaterials loaded with the drug are greatly recommended as cheap alternatives to growth factors.

Keywords: bone regeneration, cheap scaffolds, nanomaterials, active molecules

Procedia PDF Downloads 177