Search results for: multiple drug resistance

Authors: Sang-Wook Han, Zhenlan Jin, In-Hui Hwang, Chang-In Park

Abstract:

We examined structural and electrical properties of uniformly-oriented VO₂/ZnO nanostructures. VO₂ was deposited on ZnO templates by using a direct current-sputtering deposition. Scanning electron microscope and transmission electron microscope measurements indicated that b-oriented VO₂ were uniformly crystallized on ZnO templates with different lengths. VO₂/ZnO formed nanorods on ZnO nanorods with length longer than 250 nm. X-ray absorption fine structure at V K edge of VO₂/ZnO showed M1 and R phases of VO₂ at 30 and 100 ℃, respectively, suggesting structural phase transition between temperatures. Temperature-dependent resistance measurements of VO₂/ZnO nanostructures revealed metal-to-insulator transition at 65 ℃ and 55 ℃ during heating and cooling, respectively, regardless of ZnO length. The bond lengths of V-O and V-V pairs in VO₂/ZnO nanorods were somewhat distorted, and a substantial amount of structural disorder existed in the atomic pairs, compared to those of VO₂ films without ZnO. Resistance from VO₂/ZnO nanorods revealed a sharp MIT near 65 ℃ during heating and a hysteresis behavior. The resistance results suggest that microchannel for charge carriers exist nearly room temperature during cooling. VO₂/ZnO nanorods are quite stable and reproducible so that they can be widely used for practical applications to electronic devices, gas sensors, and ultra-fast switches, as examples.

Keywords: metal-to-insulator transition, VO₂, ZnO, XAFS, structural-phase transition

Procedia PDF Downloads 469

Authors: Sireen Irsheid

Abstract:

Despite concerted efforts to improve education attainment with progress in recent years, student achievement and attainment remain among the most significant challenges for school districts across the United States. Many scholars have argued that students who do not complete high school do not drop out of school voluntarily but are ‘pushed out’ of schools through multiple mechanisms related to structural and socioeconomic barriers, behavioral health challenges, pedagogical practices, and administrative procedures. Extant literature has shown that living in historically disadvantaged neighborhoods or attending under-resourced schools exacerbates student-level risk factors for grade retention and school pushout. Most efforts to respond to the school pushout phenomenon have focused on individual characteristics of students, with relatively little attention to addressing these multiple system-level characteristics related to perpetuating inequities. This study is built on a growing body of social justice-oriented research concerned with the systemic influences that shape the experiences and mental health challenges of young people. Specifically, this study examined how young people who have been experiencing education inequities make meaning and navigate the structural factors related to neighborhood and school disinvestment and access to resources and supports, and their risk for school pushout. Furthermore, schools as political, cultural, and ideologically reproductive spaces often serve as sites of resistance and can support students who are impacted by educational inequity. Study findings provide education, neighborhood, school psychology, social work practice, and policy considerations.

Keywords: education policy, mental health, school prison nexus, school pushout, structural trauma

Procedia PDF Downloads 48

Authors: Jeff Clarine, Chang-Shyh Peng, Daisy Sang

Abstract:

Bioassay is the measurement of the potency of a chemical substance by its effect on a living animal or plant tissue. Bioassay data and chemical structures from pharmacokinetic and drug metabolism screening are mined from and housed in multiple databases. Bioassay prediction is calculated accordingly to determine further advancement. This paper proposes a four-step preprocessing of datasets for improving the bioassay predictions. The first step is instance selection in which dataset is categorized into training, testing, and validation sets. The second step is discretization that partitions the data in consideration of accuracy vs. precision. The third step is normalization where data are normalized between 0 and 1 for subsequent machine learning processing. The fourth step is feature selection where key chemical properties and attributes are generated. The streamlined results are then analyzed for the prediction of effectiveness by various machine learning algorithms including Pipeline Pilot, R, Weka, and Excel. Experiments and evaluations reveal the effectiveness of various combination of preprocessing steps and machine learning algorithms in more consistent and accurate prediction.

Keywords: bioassay, machine learning, preprocessing, virtual screen

Procedia PDF Downloads 260

Authors: C. C. Egwuonwu, N. A. A. Okereke, K. O. Chilakpu, S. O. Ohanyere

Abstract:

In this study, initial soil strength indices (qu) and stress-strain characteristics, namely failure strain (ϵf), area under the stress-strain curve up to failure (Is) and stress-strain modulus between no load and failure (Es) were investigated as potential indicators for characterizing the erosion resistance of two compacted soils, namely sandy clay loam (SCL) and clay loam (CL) in some selected sites in Enugu State, Nigeria. The unconfined compressive strength (used in obtaining strength indices) and stress-strain measurements were obtained as a function of moisture content in percentage (mc %) and dry density (γd). Test were conducted over a range of 8% to 30% moisture content and 1.0 g/cm3 to 2.0 g/cm3 dry density at applied loads of 20, 40, 80, 160 and 320 kPa. Based on the results, it was found out that initial soil strength alone was not a good indicator of erosion resistance. For instance, in the comparison of exponents of mc% and γd for jet index or erosion resistance index (Ji) and the strength measurements, qu and Es agree in signs for mc%, but are opposite in signs for γd. Therefore, there is an inconsistency in exponents making it difficult to develop a relationship between the strength parameters and Ji for this data set. In contrast, the exponents of mc% and γd for Ji and ϵf and Is are opposite in signs, there is potential for an inverse relationship. The measured stress-strain characteristics, however, appeared to have potential in providing useful information on erosion resistance. The models developed for the prediction of the extent or the susceptibility of soils to erosion and subjected to sensitivity test on some selected sites achieved over 90% efficiency in their functions.

Keywords: characterization of erodibility, selected sites in Enugu state, soil strength, stress-strain indices

Procedia PDF Downloads 402

Authors: Trung Le Thanh

Abstract:

Bored piles are always the optimal solution for high-rise building foundations. They have many advantages, such as large diameter, large pile length and construction in all different geological conditions. However, due to construction characteristics, the load-bearing capacity of bored piles is not optimal because wall friction is reduced due to poor contact between the pile and the surrounding soil. Therefore, grouting technology along the pile body helps improve the load-bearing capacity of bored piles significantly through increasing the skin resistance of the pile and surrounding soil. The improvement of pile skin resistance depends on the parameters of grouting technology, especially grouting volume, mortar viscosity, mortar strength,... and different geological conditions. Studies show that the technology of grouting piles on sandy soil is more effective than on clay. This article presents an experimental model to determine the load-bearing capacity of bored piles with a diameter of 400 mm and a length of 3 m on sand with different slurry volume in Tan Uyen city, Binh Duong province. On that basis, analyze the correlation between the increase in load-bearing capacity of bored piles without and with shaft grouting pile. Research results show that the wall resistance of shaft grouted piles increases 2-3 times compared to piles without grouting, and the pile's load-bearing capacity increases significantly. The article's research provides scientific value for consulting work on the design of bored piles when grouted along the pile body.

Keywords: bored pile, shaft grouting, bearing capacity, pile shaft resistance

Procedia PDF Downloads 50

Authors: Sunil K. Jena, Sanjaya K. Samal, Mahesh Chand, Abhay T. Sangamwar

Abstract:

Tamoxifen (TMX) and its analogues are approved as a first line therapy for the treatment of estrogen receptor-positive tumors. However, clinical development of TMX has been hampered by its low bioavailability and severe hepatotoxicity. Herein, we attempt to design a new drug delivery vehicle that could enhance the pharmacokinetic performance of TMX. Initially, high-molecular weight carboxymethyl chitosan was hydrolyzed to low-molecular weight carboxymethyl chitosan (LMW CMC) with hydrogen peroxide under the catalysis of phosphotungstic acid. Amphiphilic block copolymers of LMW CMC were synthesized via amidation reaction between the carboxyl group of α-tocopherol succinate (TS) and an amine group of LMW CMC. These amphiphilic block copolymers were self-assembled to nanosize core-shell-structural micelles in the aqueous medium. The critical micelle concentration (CMC) decreased with the increasing substitution of TS on LMW CMC, which ranged from 1.58 × 10-6 to 7.94 × 10-8 g/mL. Maximum TMX loading up to 8.08 ± 0.98% was achieved with Cmc-TS4.5 (TMX/Cmc-TS4.5 with 1:8 weight ratio). Both blank and TMX-loaded polymeric micelles (TMX-PM) of Cmc-TS4.5 exhibits spherical shape with the particle size below 200 nm. TMX-PM has been found to be stable in the gastrointestinal conditions and released only 44.5% of the total drug content by the first 72 h in simulated gastric fluid (SGF), pH 1.2. However, the presence of pepsin does not significantly increased the TMX release in SGF, pH 1.2, released only about 46.2% by the first 72 h suggesting its inability to cleave the peptide bond. In contrast, the release of TMX from TMX-PM4.5 in SIF, pH 6.8 (without pancreatin) was slow and sustained, released only about 10.43% of the total drug content within the first 30 min and nearly about 12.41% by the first 72 h. The presence of pancreatin in SIF, pH 6.8 led to an improvement in drug release. About 28.09% of incorporated TMX was released in the presence of pancreatin in 72 h. A cytotoxicity study demonstrated that TMX-PM exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells. Pharmacokinetic studies on Sprague-Dawley rats revealed a remarkable increase in oral bioavailability (1.87-fold) with significant (p < 0.0001) enhancement in AUC0-72 h, t1/2 and MRT of TMX-PM4.5 than that of TMX-suspension. Thus, the results suggested that CMC-TS micelles are a promising carrier for TMX delivery.

Keywords: carboxymethyl chitosan, d-α-tocopherol succinate, pharmacokinetic, polymeric micelles, tamoxifen

Procedia PDF Downloads 316

Authors: Mehrnaz Mostafavi

Abstract:

Lung cancer is one of the most harmful forms of cancer. The long-term survival rate of lung cancer patients treated by conventional modalities such as surgical resection, radiation, and chemotherapy remains far from satisfactory. Systemic drug delivery is rarely successful because only a limited amount of the chemotherapeutic drug targets lung tumor sites, even when administered at a high dose. Targeted delivery of drug molecules to organs or special sites is one of the most challenging research areas in pharmaceutical sciences. By developing colloidal delivery systems such as liposomes, micelles and nanoparticles a new frontier was opened for improving drug delivery. Nanoparticles with their special characteristics such as small particle size, large surface area and the capability of changing their surface properties have numerous advantages compared with other delivery systems. Targeted nanoparticle delivery to the lungs is an emerging area of interest.Multimodal or combination therapy represents a promising new method to fight disease. Therefore, a combination of different therapeutic strategies may be the best alternative to improve treatment outcomes for lung cancer. Photothermal therapy was proposed as a novel approach to treatment. In this work, photothermal therapy with gold nanoparticles and near infrared laser (NIR) irradiation was investigated.Four types of small (<100nm), NIR absorbing gold nanoparticles (nanospheres, nanorods) were synthesized using wet chemical methods and characterized by transmission electron microscopy, dynamic light scattering and UV-vis spectroscopy. Their synthesis and properties were evaluated, to determine their feasibility as a photothermal agent for clinical applications. In vitro cellular uptake studies of the nanoparticles into lung cancer cell lines was measured using light scattering microscopy.Small gold nanorods had good photothermal properties and the greatest cellular uptake, and were used in photothermal studies. Under 4W laser irradiation, an increase in temperature of 10°C and decrease in cell viability of up to 80% were obtained.

Keywords: photothermal, therapy, cancer, gold nanorods

Procedia PDF Downloads 233

Authors: Jinrui Zhang, Tianlong Yang, Ying Pan

Abstract:

Methane and carbon dioxide are major greenhouse gases contributor. CO₂ dry reforming of methane (DRM) for syngas production is a promising approach to reducing global CO₂ emission and extensive utilization of natural gas. However, the reported catalysts endured rapid deactivation due to severe carbon deposition at high temperature. Here, CO₂ reduction by CH4 on hexagonal nano-nickel flakes packed by porous SiO₂ (Ni@SiO₂) catalysts driven by thermal and solar light are tested. High resistance to carbon deposition and higher reactive activity are demonstrated under focused solar light at moderate temperature (400-500 ℃). Furthermore, the photocatalytic DRM under different wavelength is investigated, and even IR irradiation can enhance the catalytic activity. The mechanism of light-enhanced reaction reactivity and equilibrium is investigated by Infrared and Raman spectroscopy, and the unique reaction pathway with light is depicted. The photo-enhanced DRM provides a promising method of renewable solar energy conversion and CO₂ emission reduction due to the excellent activity and durability.

Keywords: CO₂ emission reduction, methane, photocatalytic DRM, resistance to carbon deposition, syngas

Procedia PDF Downloads 93

Authors: Vandana T. Gawande, Kailash G. Bothara, Chandani O. Satija

Abstract:

The present research work was aimed to determine stability of cefprozil monohydrate (CEFZ) as per various stress degradation conditions recommended by International Conference on Harmonization (ICH) guideline Q1A (R2). Forced degradation studies were carried out for hydrolytic, oxidative, photolytic and thermal stress conditions. The drug was found susceptible for degradation under all stress conditions. Separation was carried out by using High Performance Thin Layer Chromatographic System (HPTLC). Aluminum plates pre-coated with silica gel 60F254 were used as the stationary phase. The mobile phase consisted of ethyl acetate: acetone: methanol: water: glacial acetic acid (7.5:2.5:2.5:1.5:0.5v/v). Densitometric analysis was carried out at 280 nm. The system was found to give compact spot for cefprozil monohydrate (0.45 Rf). The linear regression analysis data showed good linear relationship in the concentration range 200-5.000 ng/band for cefprozil monohydrate. Percent recovery for the drug was found to be in the range of 98.78-101.24. Method was found to be reproducible with % relative standard deviation (%RSD) for intra- and inter-day precision to be < 1.5% over the said concentration range. The method was validated for precision, accuracy, specificity and robustness. The method has been successfully applied in the analysis of drug in tablet dosage form. Three unknown degradation products formed under various stress conditions were isolated by preparative HPTLC and characterized by mass spectroscopic studies.

Keywords: cefprozil monohydrate, degradation products, HPTLC, stress study, stability indicating method

Procedia PDF Downloads 288

Authors: Khaled Alshammari

Abstract:

Ciprofloxacin (CIP) is a common antibiotic drug used as a strudy electron donor that interacts with dynamic π -acceptors such as 2,3-dinitrosalsylic acid (HDNS) and Tetracyanoethylene (TCNE) for synthesizing a new model of charge transfer (CT) complexes. The synthesized complexes were identified using diverse analytical methods such as UV–vis spectra, photometric titration measurements, FT-IR, HNMR Spectroscopy, and thermogravimetric analysis techniques (TGA/DTA). The stoichiometries for all the formed complexes were found to be a 1:1 M ratio between the reactants. The characteristic spectroscopic properties such as transition dipole moment (µ), oscillator strength (f), formation constant (KCT), ionization potential (ID), standard free energy (∆G), and energy of interaction (ECT) for the CT-complexes were collected. The developed CT complexes were tested for their toxicity on main organs, antimicrobial activity, antioxidant activity, and biofilm formation.

Keywords: biological, biofilm, toxicity, thermal analysis, charge transfer, spectroscopy

Procedia PDF Downloads 38

Authors: Carol Yue-En Ong, Angelina Hui-Min Tan, Quan Liu, Paul Chi-Lui Ho

Abstract:

A public general hospital in Singapore has recently implemented an automated unit-dose machine in their inpatient dispensary, Swisslog, with the objective of reducing human error and improving patient safety. However, a concern in stability arises as tablets are removed from their original packaging (bottled loose tablets/capsules) and are repackaged into individual, clear plastic wrappers as unit doses in the system. Drugs that are light-sensitive and hygroscopic would be more susceptible to degradation as the wrapper does not offer full protection. Hence, this study was carried out to study the stability of haloperidol tablets and phenytoin capsules that are light-sensitive and hygroscopic respectively. Validated HPLC-UV assays were first established for quantification of these two compounds. The medications involved were put in the Swisslog and sampled every week for one month. The collected data was analysed and showed no degradation over time. This study also explored an alternative approach for drug stability determination-Raman spectroscopy. The advantage of Raman spectroscopy is its high time efficiency and non-destructive nature. The results suggest that drug degradation can indeed be detected using Raman microscopy, but further research is needed to establish this approach for quantification or qualification of compounds. NanoRam®, a portable Raman spectrocope was also used alongside Raman microscopy but was unsuccessful in detecting degradation in this study.

Keywords: drug stability, haloperidol, HPLC, phenytoin, raman spectroscopy, Swisslog

Procedia PDF Downloads 323

Authors: Fetta Ait Ahsene-Aissat, Messaoud Hachemi, Yacine Moussaoui, Yacine Kerchiche

Abstract:

Our study focuses on two important aspects, environmental by using a sub industrial product (FAD), by economic incorporation as an addition to Portland cement, thus improving resistance to compression and bending with different proportions ADF % up to 40 additions. We studied the effect of different substitutions 0%, 10%, 20%, and 40% of additions to the mechanical effect of the mortar. We obtained a compressive strength of 61 MPa at 90 days for the cement mixture porthland FAD-40% against a resistance of 58MPa for porthland cement without addition. The flexural strength also showed a marked increase in the cement substitution. We also monitored the behavior of the mixed ash-cement by XRD analysis and scanning electron microscopy (SEM).

Keywords: FAD, porthland, flexural strength, compressive strength, DRX

Procedia PDF Downloads 336

Authors: Nabil A. Albaser

Abstract:

Background: There is a serious problem with adverse drug reactions (ADRs) everywhere, including Yemen. Since it helps with the detection, assessment, reporting and prevention of ADRs, pharmacovigilance (PV) is an essential part of the healthcare system. The unbiased reporting of ADRs remains the foundation of PV. Students majoring in healthcare should acquire the knowledge and skills necessary to conduct PV in a range of clinical settings. The primary objective of this study was to evaluate the understanding and attitudes of final-year Pharmacy, Nursing, and Midwifery students at Al-Razi University in Sana'a, Yemen, regarding PV and ADRs reporting. Methods: The study followed descriptive cross-sectional approach. A validated, self-administered questionnaire with three parts—demographic information, knowledge, and perceptions of Pharmacovigilance was online distributed to final-year Pharmacy, Nursing, and Midwifery students. The questionnaire was given to 175 students; 122 of them responded with a percentage (69.7%). Results: The majority of respondents were male (79.5%). More than the tow-third of the students, 68.9%, were beyond the age of 23. Although the majority of students, 80%, heard about the terms of ADRs and PV, but only 50% and 57.4% of the respondents, respectively, could define the both terms correctly. However, only 11.48 % of them, nevertheless, took a PV course. More than a half of them (56.6%) had a positive perceptions towards pharmacovigilance and ADR reporting and had a moderate degree of knowledge (68.9%). Conclusion: The study demonstrated that the participants lacked sufficient knowledge of pharmacovigilance and ADR reporting. They showed a moderate level of understanding of reporting ADRs as well as a favorable opinion of dealing with and reporting ADRs. Yemen's health care curriculum should include lessons on pharmacovigilance.

Keywords: adverse drug reaction reporting, pharmacovigilance, yemen, knowlegde

Procedia PDF Downloads 94

Authors: Amin Alvani

Abstract:

Multiple sclerosis (MS) is a chronic, often disabling disease in which the immune system attacks the myelin sheath of neurons in the central nervous system. The present study aimed to investigate the Relationship between behavioral inhibition/approach system (BIS-BAS) and perceived stress (PS) whit control white blood cell (WBC). 60 MS patients (male=36.7, female=63.3%; age range=15-65 participated in the study and completed the demographic questionnaire, the count blood cell (CBC) test, the behavioral Activation and behavioral inhibition scale (BIS-BAS), and the perceived stress Questionnaire (PSS-14). The results revealed that Between of BAS-reward responsiveness (BAS-DR) subscale and PS, in more than MS patient (BIS), there are increase WBC.

Keywords: behavioral inhibition/approach system, perceived stress, white blood cell, multiple sclerosis

Procedia PDF Downloads 71

Authors: M. R. Vijayakumar, K. Priyanka, Ramoji Kosuru, Lakshmi, Sanjay Singh

Abstract:

Trans resveratrol (RES) is a non-flavonoid poly-phenolic compound proved for its therapeutic and preventive effect against various types of cancer. However, the practical application of RES in cancer treatment is limited because of its higher dose (up to 7.5 g/day in humans), low biological half life, rapid metabolism and faster elimination in mammals. PEGylated core-shell type lipid polymer hybrid nanoparticles are the novel drug delivery systems for long circulation and improved anti cancer effect of its therapeutic payloads. Therefore, the main objective of this study is to extend the biological half life (long circulation) and improve the therapeutic efficacy of RES through core shell type of nanoparticles. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS), a novel surfactant is applied for the preparation of PEGylated lipid polymer hybrid nanoparticles. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Entrapment efficiency and invitro drug release were determined by ultracentrifugation method and dialysis bag method, respectively. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies after i.v administration were performed in sprague dawley rats. The prepared NPs were found to be spherical in shape with smooth surfaces. Particle size and zeta potential of prepared NPs were found to be in the range of 179.2±7.45 to 266.8±9.61 nm and -0.63 to -48.35 mV, respectively. DSC revealed absence of potential interaction. XRD study revealed presence of amorphous form in nanoparticles. Entrapment efficiency was found to be 83.7 % and drug release was found to be in controlled manner. MTT assay showed low MEC and pharmacokinetic studies showed higher AUC of nanoformulaition than its pristine drug. All these studies revealed that the RES loaded PEG modified core-shell type lipid polymer hybrid nanoparticles can be an alternative tool for chemopreventive and therapeutic application of RES in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating nanoparticles, bioavailability enhancement, core shell nanoparticles, lipid polymer hybrid nanoparticles

Procedia PDF Downloads 455

Authors: Marta Skwarecka, Patrycja Bloch, Rafal Walkusz, Oliwia Urbanowicz, Grzegorz Zielinski, Sabina Zoledowska, Dawid Nidzworski

Abstract:

Upper respiratory tract infections are one of the most common reasons for visiting a general doctor. Streptococci are the most common bacterial etiological factors in these infections. There are many different types of Streptococci and infections vary in severity from mild throat infections to pneumonia. For example, S. pyogenes mainly contributes to acute pharyngitis, palatine tonsils and scarlet fever, whereas S. Streptococcus pneumoniae is responsible for several invasive diseases like sepsis, meningitis or pneumonia with high mortality and dangerous complications. There are only a few diagnostic tests designed for detection Streptococci from the infected throat of patients. However, they are mostly based on lateral flow techniques, and they are not used as a standard due to their low sensitivity. The diagnostic standard is to culture patients throat swab on semi selective media in order to multiply pure etiological agent of infection and subsequently to perform antibiogram, which takes several days from the patients visit in the clinic. Therefore, the aim of our studies is to develop and implement to the market a Point of Care device for the rapid identification of Streptococcus pyogenes and Streptococcus pneumoniae with simultaneous identification of antibiotic resistance genes. In the course of our research, we successfully selected genes for to-species identification of Streptococci and genes encoding antibiotic resistance proteins. We have developed a reaction to amplify these genes, which allows detecting the presence of S. pyogenes or S. pneumoniae followed by testing their resistance to erythromycin, chloramphenicol and tetracycline. What is more, the detection of β-lactamase-encoding genes that could protect Streptococci against antibiotics from the ampicillin group, which are widely used in the treatment of this type of infection is also developed. The test is carried out directly from the patients' swab, and the results are available after 20 to 30 minutes after sample subjection, which could be performed during the medical visit.

Keywords: antibiotic resistance, Streptococci, respiratory infections, diagnostic test

Procedia PDF Downloads 114

Authors: Shaimaa Eltanani, Thangal Yumnamcha, Ahmed S. Ibrahim

Abstract:

Purpose: Mitochondria dysfunction is central to breaking the barrier integrity of retinal endothelial cells (RECs) in various blinding eye diseases such as diabetic retinopathy and retinopathy of prematurity. Therefore, we aimed to dissect the role of different mitochondrial components, specifically, those of oxidative phosphorylation (OxPhos), in maintaining the barrier function of RECs. Methods: Electric cell-substrate impedance sensing (ECIS) technology was used to assess in real-time the role of different mitochondrial components in the total impedance (Z) of human RECs (HRECs) and its components; the capacitance (C) and the total resistance (R). HRECs were treated with specific mitochondrial inhibitors that target different steps in OxPhos: Rotenone for complex I; Oligomycin for ATP synthase; and FCCP for uncoupling OxPhos. Furthermore, data were modeled to investigate the effects of these inhibitors on the three parameters that govern the total resistance of cells: cell-cell interactions (Rb), cell-matrix interactions (α), and cell membrane permeability (Cm). Results: Rotenone (1 µM) produced the greatest reduction in the Z, followed by FCCP (1 µM), whereas no reduction in the Z was observed after the treatment with Oligomycin (1 µM). Following this further, we deconvoluted the effect of these inhibitors on Rb, α, and Cm. Firstly, rotenone (1 µM) completely abolished the resistance contribution of Rb, as the Rb became zero immediately after the treatment. Secondly, FCCP (1 µM) eliminated the resistance contribution of Rb only after 2.5 hours and increased Cm without considerable effect on α. Lastly, Oligomycin had the lowest impact among these inhibitors on Rb, which became similar to the control group at the end of the experiment without noticeable effects on Cm or α. Conclusion: These results demonstrate differential roles for complex I, complex V, and coupling of OxPhos in maintaining the barrier functionality of HRECs, in which complex I being the most important component in regulating the barrier functionality and the spreading behavior of HRECs. Such differences can be used in investigating gene expression as well as for screening selective agents that improve the functionality of complex I to be used in the therapeutic approach for treating REC-related retinal diseases.

Keywords: human retinal endothelial cells (hrecs), rotenone, oligomycin, fccp, oxidative phosphorylation, oxphos, capacitance, impedance, ecis modeling, rb resistance, α resistance, and barrier integrity

Procedia PDF Downloads 82

Authors: Marcio S. da Silva, Jose Mauricio de B. Bezerra, Antonio E. de A. Nogueira

Abstract:

This paper aims to make a performance analysis of shield wire transmission lines against atmospheric discharges when it is made the option of sectioning the shield wire and verify if the tolerability of the change. As a goal of this work, it was established to make complete modeling of a transmission line in the ATPDraw program with shield wire grounded in all the towers and in some towers. The methodology used to make the proposed evaluation was to choose an actual transmission line that served as a case study. From the choice of transmission line and verification of all its topology and materials, complete modeling of the line using the ATPDraw software was performed. Then several atmospheric discharges were simulated by striking the grounded shield wires in each tower. These simulations served to identify the behavior of the existing line against atmospheric discharges. After this first analysis, the same line was reconsidered with shield wire segmentation. The shielding wire segmentation technique aims to reduce induced losses in shield wires and is adopted in some transmission lines in Brazil. With the same conditions of atmospheric discharge the transmission line, this time with shield wire segmentation was again evaluated. The results obtained showed that it is possible to obtain similar performances against atmospheric discharges between a shield wired line in multiple towers and the same line with shield wire segmentation if some precautions are adopted as verification of the ground resistance of the wire segmented shield, adequacy of the maximum length of the segmented gap, evaluation of the separation length of the electrodes of the insulator spark, among others. As a conclusion, it is verified that since the correct assessment and adopted the correct criteria of adjustment a transmission line with shielded wire segmentation can perform very similar to the traditional use with multiple earths. This solution contributes in a very important way to the reduction of energy losses in transmission lines.

Keywords: atmospheric discharges, ATPDraw, shield wire, transmission lines

Procedia PDF Downloads 154

Authors: Chang-Hwan Oh, Young-Jong Lee

Abstract:

In April, 2015, the Ministry of Food and Drug Safety’s announcement that only 10 of the 207 products that list Cynanchum Wilfordii Radix among their ingredients were confirmed to actually contain “iyeobupiso” the counterfeit version of the “baeksuo” raised a fog to consumers who purchased health/functional foods supposedly containing the herbal medicinal material, “baeksuo” in Korean. Baeksuo is the main ingredient of the product “EstroG-100” that contain Phlomis umbrosa and Angelica gigas too (NaturalEndoTech, S.Korea). The hot water extract of the herbal medicinal materials (HMM) was approved as a product specific Health/Functional Food (HFF) having a helpful function to women reaching menopause by Korea Food & Drug Administration (Ministry of Food & Drug Safety at present). The origin of “baeksuo” is the root of Cynanchum wilfordii Hemsley in Korea (But “iyeobupiso, the root of Cynanchum auriculatum Royle ex Wight is considered as the origin of “baeksuo” in China). In Korea, about 116 HMMs are listed as the food materials in Korea Food Code among the total 187 HMMs could be used for food and medicine purpose simultaneously. But there are some chances of the HMMs (shared use for food and medicine purpose) could be misused by the part and HMMs not permitted for HFF such as the “baeksuo” case. In this study, some of HMMs (shared use for food and medicine purpose) are examined to alleviate the misuse chance of HMMs for HFFs in Korea. For the purpose of this study, the origin, shape, edible parts, efficacy and the side effects of the similar HMMs to be misused for HFF are investigated.

Keywords: herbal medicinal materials, healthy/functional foods, misuse, shared use

Procedia PDF Downloads 277

Authors: Ayyoub Jamali

Abstract:

At the first glance, it seems that the African Court on Human and People’s Rights has achieved a tremendous development in the protection of human rights in Africa. Since its first judgement in 2009, the court has taken a robust approach/ assertive stance, showing its strength by finding states to be in violation of the Africana Charter and other human rights treaties. This paper seeks to discuss various challenges and resistance that the Court has faced since the adoption of the Founding Protocol to the Establishment of the African Court on Human and People’s Rights. The outcome of the paper casts shadow on the legitimacy and effectiveness of the African Court as the guarantor of human rights within the African continent.

Keywords: African Court on Human and People’s Rights, African Union, African regional human rights system, compliance

Procedia PDF Downloads 138

Authors: Seolah Lee, Yoohyk Jang, Soyoung Lee, Kon Chu, Sang Kun Lee

Abstract:

Objective: The International League Against Epilepsy (ILAE) currently suggests a topiramate serum level range of 5-20 mg/L. However, numerous institutions have observed substantial drug response at lower levels. This study aims to investigate the correlation between topiramate serum levels, drug responsiveness, and adverse events to establish a more accurate and tailored therapeutic range. Methods: We retrospectively analyzed topiramate serum samples collected between January 2017 and January 2022 at Seoul National University Hospital. Clinical data, including serum levels, antiseizure regimens, seizure frequency, and adverse events, were collected. Patient responses were categorized as "insufficient" (reduction in seizure frequency <50%) or "sufficient" (reduction ≥ 50%). Within the "sufficient" group, further subdivisions included seizure-free and tolerable seizure subgroups. A population pharmacokinetic model estimated serum levels from spot measurements. ROC curve analysis determined the optimal serum level cut-off. Results: A total of 389 epilepsy patients, with 555 samples, were reviewed, having a mean dose of 178.4±117.9 mg/day and a serum level of 3.9±2.8 mg/L. Out of the samples, only 5.6% (n=31) exhibited insufficient response, with a mean serum level of 3.6±2.5 mg/L. In contrast, 94.4% (n=524) of samples demonstrated sufficient response, with a mean serum level of 4.0±2.8 mg/L. This difference was not statistically significant (p = 0.45). Among the 78 reported adverse events, logistic regression analysis identified a significant association between ataxia and serum concentration (p = 0.04), with an optimal cut-off value of 6.5 mg/L. In the subgroup of patients receiving monotherapy, those in the tolerable seizure group exhibited a significantly higher serum level compared to the seizure-free group (4.8±2.0 mg/L vs 3.4±2.3 mg/L, p < 0.01). Notably, patients in the tolerable seizure group displayed a higher likelihood of progressing into drug-resistant epilepsy during follow-up visits compared to the seizure-free group. Significance: This study proposed an optimal therapeutic concentration for topiramate based on the patient's responsiveness to the drug and the incidence of adverse effects. We employed a population pharmacokinetic model and analyzed topiramate serum levels to recommend a serum level below 6.5 mg/L to mitigate the risk of ataxia-related side effects. Our findings also indicated that topiramate dose elevation is unnecessary for suboptimal responders, as the drug's effectiveness plateaus at minimal doses.

Keywords: topiramate, therapeutic range, low dos, antiseizure effect

Procedia PDF Downloads 42

Authors: Prasamsha Panta, Da Yeon Kim, Ja Yong Jang, Min Jae Kim, Jae Ho Kim, Moon Suk Kim

Abstract:

Introduction: Among the many anticancer drugs used clinically, doxorubicin (Dox), was one of widely used drugs to treat many types of solid tumors such as liver, colon, breast, or lung. Intratumoral injection of chemotherapeutic agents is a potentially more effective alternative to systemic administration because direct delivery of the anticancer drug to the target may improve both the stability and efficacy of anticancer drugs. Injectable in situ-forming gels have attracted considerable attention because they can achieve site specific drug delivery, long term action periods, and improved patient compliance. Objective: Objective of present study is to confirm clinical benefit of intratumoral chemotherapy using injectable in situ-forming poly(ethylene glycol)-b-polycaprolactone diblock copolymer (MP) and Dox with increase in efficacy and reducing the toxicity in patients with cancer diseases. Methods and methodology: We prepared biodegradable MP hydrogel and measured viscosity for the evaluation of thermo-sensitive property. In vivo antitumor activity was performed with normal saline, MP only, single free Dox, repeat free Dox, and Dox-loaded MP gel. The remaining amount of Dox drug was measured using HPLC after the mouse was sacrified. For cytotoxicity studies WST-1 assay was performed. Histological analysis was done with H&E and TUNEL processes respectively. Results: The works in this experiment showed that Dox-loaded MP have biodegradable drug depot property. Dox-loaded MP gels showed remarkable in vitro cytotoxicity activities against cancer cells. Finally, this work indicates that injection of Dox-loaded MP allowed Dox to act effectively in the tumor and induced long-lasting supression of tumor growth. Conclusion: This work has examined the potential clinical utility of intratumorally injected Dox-loaded MP gel, which shows significant effect of higher local Dox retention compared with systemically administered Dox.

Keywords: injectable in-situ forming hydrogel, anticancer, doxorubicin, intratumoral injection

Procedia PDF Downloads 390

Authors: Chao-xun Liu, Shi-hong Lu

Abstract:

In spite of its importance to the aerospace and automobile industries, little or no attention has been devoted to the accurate modeling of the ultrasonic shot peening (USP) process. It is therefore the purpose of this study to conduct finite element analysis of the process using a realistic multiple pin impacts model with the explicit solver of ABAQUS. In this paper, we research the effect of several key parameters on the residual stress distribution within the target, including impact velocity, incident angle, friction coefficient between pins and target and impact number of times were investigated. The results reveal that the impact velocity and impact number of times have obvious effect and impacting vertically could produce the most perfect residual stress distribution. Then we compare the results with the date in USP experiment and verify the exactness of the model. The analysis of the multiple pin impacts date reveal the relationships between peening process parameters and peening quality, which are useful for identifying the parameters which need to be controlled and regulated in order to produce a more beneficial compressive residual stress distribution within the target.

Keywords: ultrasonic shot peening, finite element, multiple pins, residual stress, numerical simulation

Procedia PDF Downloads 435

Authors: Paresh M. Patel, Amit A. Patel, R. H. Parikh

Abstract:

The present investigation was undertaken to fabricate modified transport fluconazole that belongs to BCS class II and have a poor applicability on topical infection. So to improve topical application, transdermal spray could play a vital role by using ethyl cellulose and Eudragit® S100 as film-forming polymers. Concentration of Eudragit® S100, ethyl cellulose and permeation enhancer (camphor and menthol) were selected as independent variables, whereas drying time, viscosity and in-vitro drug release were selected as dependent variables in factorial design. The viscosity, drying time and in-vitro drug release of the optimize batch B15 was 40.1 cps, 47 sec. and 90.79% respectively. The film of optimized batch was flexible and dermal-adhesive.

Keywords: Eudragit, ethyl cellulose, fluconazole, transdermal spray

Procedia PDF Downloads 440

Authors: Swapnila V. Shinde, Hemant P. Joshi, Sumit R. Dhas, Dhananjaysingh B. Rajput

Abstract:

The objective of the present study is to develop hydro-dynamically balanced system for atenolol, β-blocker as a single unit floating tablet. Atenolol shows pH dependent solubility resulting into a bioavailability of 36%. Thus, site specific oral controlled release floating drug delivery system was developed. Formulation includes novice use of rate controlling polymer such as locust bean gum (LBG) in combination of HPMC K4M and gas generating agent sodium bicarbonate. Tablet was prepared by direct compression method and evaluated for physico-mechanical properties. The statistical method was utilized to optimize the effect of independent variables, namely amount of HPMC K4M, LBG and three dependent responses such as cumulative drug release, floating lag time, floating time. Graphical and mathematical analysis of the results allowed the identification and quantification of the formulation variables influencing the selected responses. To study the gastrointestinal transit of the optimized gastro-retentive formulation, in vivo gamma scintigraphy was carried out in six healthy rabbits, after radio labeling the formulation with 99mTc. The transit profiles demonstrated that the dosage form was retained in the stomach for more than 5 hrs. The study signifies the potential of the developed system for stomach targeted delivery of atenolol with improved bioavailability.

Keywords: floating tablet, factorial design, gamma scintigraphy, antihypertensive model drug, HPMC, locust bean gum

Procedia PDF Downloads 267

Authors: Ye Jiang

Abstract:

To examine how the relationships among multiple institutional logics vary over time and the factors that may impact this process, we conducted a 15-year in-depth longitudinal case study of a Higher Education Institution to examine its exploration in college student management. By employing constructive grounded theory, we developed a four-stage process model comprising separation, formalization, selective bridging, and embeddedness that showed how two contradictory logics become complementary, and finally become a new hybridized logic. We argue that selective bridging is an important step in changing inter-logic relations. We also found that ambidextrous leadership and situational sensemaking are two key factors that drive this process. Our contribution to the literature is threefold. First, we enhance the literature on the changing relationships among multiple institutional logics and our findings advance the understanding of relationships between multiple logics through a dynamic view. While most studies have tended to assume that the relationship among logics is static and persistently in a contentious state, we contend that the relationships among multiple institutional logics can change over time. Competitive logics can become complementary, and a new hybridized logic can emerge therefrom. The four-stage logic hybridization process model offers insights on the logic hybridization process, which is underexplored in the literature. Second, our research reveals that selective bridging is important in making conflicting logics compatible, and thus constitutes a key step in creating new hybridized logic dynamics. Our findings suggest that the relations between multiple logics are manageable and can thus be manipulated for organizational innovation. Finally, the factors influencing the variations in inter-logic relations enrich the understanding of the antecedents of these dynamics.

Keywords: institutional theory, institutional logics, ambidextrous leadership, situational sensemaking

Procedia PDF Downloads 131

Authors: Buta Singh Sidhu, Sukhpal Singh Chatha, Hazoor Singh Sidhu

Abstract:

In the present investigation, 75Cr3C2-25NiCr coating was deposited on T91 boiler tube steel substrate by high velocity oxy-fuel (HVOF) process to enhance high-temperature corrosion resistance. High-temperature performance of bare, as well as HVOF-coated steel specimens was evaluated for 1500 h under cyclic conditions in the platen superheater zone coal-fired boiler, where the temperature was around 900 °C. Experiments were carried out for 15 cycles each of 100 h duration followed by 1 h cooling at ambient temperature. The performance of the bare and coated specimens was assessed via metal thickness loss corresponding to the corrosion scale formation and the depth of internal corrosion attack. 75Cr3C2-25NiCr coating deposited on T91 steel imparted better hot corrosion resistance than the uncoated steel. Inferior resistance of bare T91 steel is attributed to the formation of pores and loosely bounded oxide scale rich in Fe2O3.

Keywords: 75Cr3C2-25NiCr, HVOF process, boiler steel, coal fired boilers

Procedia PDF Downloads 590

Authors: Yu Chen, Seong-Jin Kim, Jaehoon Chung

Abstract:

High throughput cells counting and sizing are often required for biomedical applications. Here we report design, fabrication and validating of a micro-machined Coulter counter device with multiple-channel to realize such application for low cost. Multiple vertical through-holes were fabricated on a silicon chip, combined with the PDMS micro-fluidics channel that serves as the sensing channel. In order to avoid the crosstalk introduced by the electrical connection, instead of measuring the current passing through, the potential of each channel is monitored, thus the high throughput is possible. A peak of the output potential can be captured when the cell/particle is passing through the microhole. The device was validated by counting and sizing the polystyrene beads with diameter of 6 μm, 10 μm and 15 μm. With the sampling frequency to be set at 100 kHz, up to 5000 counts/sec for each channel can be realized. The counting and enumeration of MCF7 cancer cells are also demonstrated.

Keywords: Coulter counter, cell enumeration, high through-put, cell sizing

Procedia PDF Downloads 598

Authors: Seyran Naghdi

Abstract:

Background: Orphan drug development is limited by very high costs attributed to the research and development and small size market. How health policymakers address this challenge to consider both supply and demand sides need to be explored for directing the policies and plans in the right way. The price is an important signal for pharmaceutical companies’ profitability and the patients’ accessibility as well. Objective: This study aims to find out the orphan drugs' price-setting patterns and approaches in health systems through a systematic review of the available evidence. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach was used. MedLine, Embase, and Web of Sciences were searched via appropriate search strategies. Through Medical Subject Headings (MeSH), the appropriate terms for pricing were 'cost and cost analysis', and it was 'orphan drug production', and 'orphan drug', for orphan drugs. The critical appraisal was performed by the Joanna-Briggs tool. A Cochrane data extraction form was used to obtain the data about the studies' characteristics, results, and conclusions. Results: Totally, 1,197 records were found. It included 640 hits from Embase, 327 from Web of Sciences, and 230 MedLine. After removing the duplicates, 1,056 studies remained. Of them, 924 studies were removed in the primary screening phase. Of them, 26 studies were included for data extraction. The majority of the studies (>75%) are from developed countries, among them, approximately 80% of the studies are from European countries. Approximately 85% of evidence has been produced in the recent decade. Conclusions: There is a huge variation of price-setting among countries, and this is related to the specific pharmacological market structure and the thresholds that governments want to intervene in the process of pricing. On the other hand, there is some evidence on the availability of spaces to reduce the very high costs of orphan drugs development through an early agreement between pharmacological firms and governments. Further studies need to focus on how the governments could incentivize the companies to agree on providing the drugs at lower prices.

Keywords: orphan drugs, orphan drug production, pricing, costs, cost analysis

Procedia PDF Downloads 152

Authors: Kohkan Shamsi

Abstract:

Background: MRI and PET are now extensively utilized in Alzheimer's disease (AD) trials for patient eligibility, efficacy assessment, and safety evaluations but including imaging in AD trials impacts site selection process, patient recruitment, and patient retention. Methods: PET/MRI are performed at baseline and at multiple follow-up timepoints. This requires prospective site imaging qualification, evaluation of phantom data, training and continuous monitoring of machines for acquisition of standardized and consistent data. This also requires prospective patient/caregiver training as patients must go to multiple facilities for imaging examinations. We will share our experience form one of the largest AD programs. Lesson learned: Many neurological diseases have a similar presentation as AD or could confound the assessment of drug therapy. The inclusion of wrong patients has ethical and legal issues, and data could be excluded from the analysis. Centralized eligibility evaluation read process will be discussed. Amyloid related imaging abnormalities (ARIA) were observed in amyloid-β trials. FDA recommended regular monitoring of ARIA. Our experience in ARIA evaluations in large phase III study at > 350 sites will be presented. Efficacy evaluation: MRI is utilized to evaluate various volumes of the brain. FDG PET or amyloid PET agents has been used in AD trials. We will share our experience about site and central independent reads. Imaging logistic issues that need to be handled in the planning phase will also be discussed as it can impact patient compliance thereby increasing missing data and affecting study results. Conclusion: imaging must be prospectively planned to include standardizing imaging methodologies, site selection process and selecting assessment criteria. Training should be transparently conducted and documented. Prospective patient/caregiver awareness of imaging requirement is essential for patient compliance and reduction in missing imaging data.

Keywords: Alzheimer's disease, ARIA, MRI, PET, patient recruitment, retention

Procedia PDF Downloads 102