Search results for: drug loading
Commenced in January 2007
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Edition: International
Paper Count: 3484

Search results for: drug loading

2194 Studies on Organic and Inorganic Micro/Nano Particle Reinforced Epoxy Composites

Authors: Daniel Karthik, Vijay Baheti, Jiri Militky, Sundaramurthy Palanisamy

Abstract:

Fibre based nano particles are presently considered as one of the potential filler materials for the improvement of mechanical and physical properties of polymer composites. Due to high matrix-filler interfacial area there will be uniform and homogeneous dispersion of nanoparticles. In micro/nano filler reinforced composites, resin material is usually tailored by organic or inorganic nanoparticles to have improved matrix properties. The objective of this study was to compare the potential of reinforcement of different organic and inorganic micro/nano fillers in epoxy composites. Industrial and agricultural waste of fibres like Agave Americana, cornhusk, jute, basalt, carbon, glass and fly ash was utilized to prepare micro/nano particles. Micro/nano particles were obtained using high energy planetary ball milling process in dry condition. Milling time and ball size were kept constant throughout the ball milling process. Composites were fabricated by hand lay method. Particle loading was kept constant to 3% wt. for all composites. In present study, loading of fillers was selected as 3 wt. % for all composites. Dynamic mechanical properties of the nanocomposite films were performed in three-point bending mode with gauge length and sample width of 50 mm and 10 mm respectively. The samples were subjected to an oscillating frequency of 1 Hz, 5 Hz and 10 Hz and 100 % oscillating amplitude in the temperature ranges of 30°C to 150°C at the heating rate of 3°C/min. Damping was found to be higher with the jute composites. Amongst organic fillers lowest damping factor was observed with Agave Americana particles, this means that Agave americana fibre particles have betters interface adhesion with epoxy resin. Basalt, fly ash and glass particles have almost similar damping factors confirming better interface adhesion with epoxy.

Keywords: ball milling, damping factor, matrix-filler interface, particle reinforcements

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2193 A Computational Investigation of Potential Drugs for Cholesterol Regulation to Treat Alzheimer’s Disease

Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

Abstract:

Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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2192 Parameters Influencing Human Machine Interaction in Hospitals

Authors: Hind Bouami

Abstract:

Handling life-critical systems complexity requires to be equipped with appropriate technology and the right human agents’ functions such as knowledge, experience, and competence in problem’s prevention and solving. Human agents are involved in the management and control of human-machine system’s performance. Documenting human agent’s situation awareness is crucial to support human-machine designers’ decision-making. Knowledge about risks, critical parameters and factors that can impact and threaten automation system’s performance should be collected using preventive and retrospective approaches. This paper aims to document operators’ situation awareness through the analysis of automated organizations’ feedback. The analysis of automated hospital pharmacies feedbacks helps to identify and control critical parameters influencing human machine interaction in order to enhance system’s performance and security. Our human machine system evaluation approach has been deployed in Macon hospital center’s pharmacy which is equipped with automated drug dispensing systems since 2015. Automation’s specifications are related to technical aspects, human-machine interaction, and human aspects. The evaluation of drug delivery automation performance in Macon hospital center has shown that the performance of the automated activity depends on the performance of the automated solution chosen, and also on the control of systemic factors. In fact, 80.95% of automation specification related to the chosen Sinteco’s automated solution is met. The performance of the chosen automated solution is involved in 28.38% of automation specifications performance in Macon hospital center. The remaining systemic parameters involved in automation specifications performance need to be controlled.

Keywords: life-critical systems, situation awareness, human-machine interaction, decision-making

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2191 Investigation of Interlayer Shear Effects in Asphalt Overlay on Existing Rigid Airfield Pavement Using Digital Image Correlation

Authors: Yuechao Lei, Lei Zhang

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The interface shear between asphalt overlay and existing rigid airport pavements occurs due to differences in the mechanical properties of materials subjected to aircraft loading. Interlayer contact influences the mechanical characteristics of the asphalt overlay directly. However, the effective interlayer relative displacement obtained accurately using existing displacement sensors of the loading apparatus remains challenging. This study aims to utilize digital image correlation technology to enhance the accuracy of interfacial contact parameters by obtaining effective interlayer relative displacements. Composite structure specimens were prepared, and fixtures for interlayer shear tests were designed and fabricated. Subsequently, a digital image recognition scheme for required markers was designed and optimized. Effective interlayer relative displacement values were obtained through image recognition and calculation of surface markers on specimens. Finite element simulations validated the mechanical response of composite specimens with interlayer shearing. Results indicated that an optimized marking approach using the wall mending agent for surface application and color coding enhanced the image recognition quality of marking points on the specimen surface. Further image extraction provided effective interlayer relative displacement values during interlayer shear, thereby improving the accuracy of interface contact parameters. For composite structure specimens utilizing Styrene-Butadiene-Styrene (SBS) modified asphalt as the tack coat, the corresponding maximum interlayer shear stress strength was 0.6 MPa, and fracture energy was 2917 J/m2. This research provides valuable insights for investigating the impact of interlayer contact in composite pavement structures on the mechanical characteristics of asphalt overlay.

Keywords: interlayer contact, effective relative displacement, digital image correlation technology, composite pavement structure, asphalt overlay

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2190 Effect of Graphene on the Structural and Optical Properties of Ceria:Graphene Nanocomposites

Authors: R. Udayabhaskar, R. V. Mangalaraja, V. T. Perarasu, Saeed Farhang Sahlevani, B. Karthikeyan, David Contreras

Abstract:

Bandgap engineering of CeO₂ nanocrystals is of high interest for many research groups to meet the requirement of desired applications. The band gap of CeO₂ nanostructures can be modified by varying the particle size, morphology and dopants. Anchoring the metal oxide nanostructures on graphene sheets will result in composites with improved properties than the parent materials. The presence of graphene sheets will acts a support for the growth, influences the morphology and provides external paths for electronic transitions. Thus, the controllable synthesis of ceria:graphene composites with various morphologies and the understanding of the optical properties is highly important for the usage of these materials in various applications. The development of ceria and ceria:graphene composites with low cost, rapid synthesis with tunable optical properties is still desirable. By this work, we discuss the synthesis of pure ceria (nanospheres) and ceria:graphene composites (nano-rice like morphology) by using commercial microwave oven as a cost effective and environmentally friendly approach. The influence of the graphene on the crystallinity, morphology, band gap and luminescence of the synthesized samples were analyzed. The average crystallite size obtained by using Scherrer formula of the CeO₂ nanostructures showed a decreasing trend with increasing the graphene loading. The higher graphene loaded ceria composite clearly depicted morphology of nano-rice like in shape with the diameter below 10 nm and the length over 50 nm. The presence of graphene and ceria related vibrational modes (100-4000 cm⁻¹) confirmed the successful formation of composites. We observed an increase in band gap (blue shift) with increasing loading amount of graphene. Further, the luminescence related to various F-centers was quenched in the composites. The authors gratefully acknowledge the FONDECYT Project No.: 3160142 and BECA Conicyt National Doctorado2017 No. 21170851 Government of Chile, Santiago, for the financial assistance.

Keywords: ceria, graphene, luminescence, blue shift, band gap widening

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2189 Free Energy Computation of A G-Quadruplex-Ligand Structure: A Classical Molecular Dynamics and Metadynamics Simulation Study

Authors: Juan Antonio Mondragon Sanchez, Ruben Santamaria

Abstract:

The DNA G-quadruplex is a four-stranded DNA structure formed by stacked planes of four base paired guanines (G-quartet). Guanine rich DNA sequences appear in many sites of genomic DNA and can potential form G-quadruplexes, such as those occurring at 3'-terminus of the human telomeric DNA. The formation and stabilization of a G-quadruplex by small ligands at the telomeric region can inhibit the telomerase activity. In turn, the ligands can be used to down regulate oncogene expression making G-quadruplex an attractive target for anticancer therapy. Many G-quadruplex ligands have been proposed with a planar core to facilitate the pi–pi stacking and electrostatic interactions with the G-quartets. However, many drug candidates are impossibilitated to discriminate a G-quadruplex from a double helix DNA structure. In this context, it is important to investigate the site topology for the interaction of a G-quadruplex with a ligand. In this work, we determine the free energy surface of a G-quadruplex-ligand to study the binding modes of the G-quadruplex (TG4T) with the daunomycin (DM) drug. The complex TG4T-DM is studied using classical molecular dynamics in combination with metadynamics simulations. The metadynamics simulations permit an enhanced sampling of the conformational space with a modest computational cost and obtain free energy surfaces in terms of the collective variables (CV). The free energy surfaces of TG4T-DM exhibit other local minima, indicating the presence of additional binding modes of daunomycin that are not observed in short MD simulations without the metadynamics approach. The results are compared with similar calculations on a different structure (the mutated mu-G4T-DM where the 5' thymines on TG4T-DM have been deleted). The results should be of help to design new G-quadruplex drugs, and understand the differences in the recognition topology sites of the duplex and quadruplex DNA structures in their interaction with ligands.

Keywords: g-quadruplex, cancer, molecular dynamics, metadynamics

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2188 Conceptual and Preliminary Design of Landmine Searching UAS at Extreme Environmental Condition

Authors: Gopalasingam Daisan

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Landmines and ammunitions have been creating a significant threat to the people and animals, after the war, the landmines remain in the land and it plays a vital role in civilian’s security. Especially the Children are at the highest risk because they are curious. After all, an unexploded bomb can look like a tempting toy to an inquisitive child. The initial step of designing the UAS (Unmanned Aircraft Systems) for landmine detection is to choose an appropriate and effective sensor to locate the landmines and other unexploded ammunitions. The sensor weight and other components related to the sensor supporting device’s weight are taken as a payload weight. The mission requirement is to find the landmines in a particular area by making a proper path that will cover all the vicinity in the desired area. The weight estimation of the UAV (Unmanned Aerial Vehicle) can be estimated by various techniques discovered previously with good accuracy at the first phase of the design. The next crucial part of the design is to calculate the power requirement and the wing loading calculations. The matching plot techniques are used to determine the thrust-to-weight ratio, and this technique makes this process not only easiest but also precisely. The wing loading can be calculated easily from the stall equation. After these calculations, the wing area is determined from the wing loading equation and the required power is calculated from the thrust to weight ratio calculations. According to the power requirement, an appropriate engine can be selected from the available engine from the market. And the wing geometric parameter is chosen based on the conceptual sketch. The important steps in the wing design to choose proper aerofoil and which will ensure to create sufficient lift coefficient to satisfy the requirements. The next component is the tail; the tail area and other related parameters can be estimated or calculated to counteract the effect of the wing pitching moment. As the vertical tail design depends on many parameters, the initial sizing only can be done in this phase. The fuselage is another major component, which is selected based on the slenderness ratio, and also the shape is determined on the sensor size to fit it under the fuselage. The landing gear is one of the important components which is selected based on the controllability and stability requirements. The minimum and maximum wheel track and wheelbase can be determined based on the crosswind and overturn angle requirements. The minor components of the landing gear design and estimation are not the focus of this project. Another important task is to calculate the weight of the major components and it is going to be estimated using empirical relations and also the mass is added to each such component. The CG and moment of inertia are also determined to each component separately. The sensitivity of the weight calculation is taken into consideration to avoid extra material requirements and also reduce the cost of the design. Finally, the aircraft performance is calculated, especially the V-n (velocity and load factor) diagram for different flight conditions such as not disturbed and with gust velocity.

Keywords: landmine, UAS, matching plot, optimization

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2187 FEM Simulation of Tool Wear and Edge Radius Effects on Residual Stress in High Speed Machining of Inconel718

Authors: Yang Liu, Mathias Agmell, Aylin Ahadi, Jan-Eric Stahl, Jinming Zhou

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Tool wear and tool geometry have significant effects on the residual stresses in the component produced by high-speed machining. In this paper, Coupled Eulerian and Lagrangian (CEL) model is adopted to investigate the residual stress in high-speed machining of Inconel718 with a CBN170 cutting tool. The result shows that the mesh with the smallest size of 5 um yields cutting forces and chip morphology in close agreement with the experimental data. The analysis of thermal loading and mechanical loading are performed to study the effect of segmented chip morphology on the machined surface topography and residual stress distribution. The effects of cutting edge radius and flank wear on residual stresses formation and distribution on the workpiece were also investigated. It is found that the temperature within 100um depth of the machined surface increases drastically due to the more friction heat generation with the contact area of tool and workpiece increasing when a larger edge radius and flank wear are used. With the depth further increasing, the temperature drops rapidly for all cases due to the low conductivity of Inconel718. Consequently, higher and deeper tensile residual stress is generated on the superficial. Furthermore, an increased depth of plastic deformation and compressive residual stress is noticed in the subsurface, which is attributed to the reduction of the yield strength under the thermal effect. Besides, the ploughing effect produced by a larger tool edge radius contributes more than flank wear. The magnitude variation of the compressive residual stress caused by various edge radius and flank wear have a totally opposite trend, which depends on the magnitude of the ploughing and friction pressure acting on the machined surface.

Keywords: Coupled Eulerian Lagrangian, segmented chip, residual stress, tool wear, edge radius, Inconel718

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2186 An Automated Magnetic Dispersive Solid-Phase Extraction Method for Detection of Cocaine in Human Urine

Authors: Feiyu Yang, Chunfang Ni, Rong Wang, Yun Zou, Wenbin Liu, Chenggong Zhang, Fenjin Sun, Chun Wang

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Cocaine is the most frequently used illegal drug globally, with the global annual prevalence of cocaine used ranging from 0.3% to 0.4 % of the adult population aged 15–64 years. Growing consumption trend of abused cocaine and drug crimes are a great concern, therefore urine sample testing has become an important noninvasive sampling whereas cocaine and its metabolites (COCs) are usually present in high concentrations and relatively long detection windows. However, direct analysis of urine samples is not feasible because urine complex medium often causes low sensitivity and selectivity of the determination. On the other hand, presence of low doses of analytes in urine makes an extraction and pretreatment step important before determination. Especially, in gathered taking drug cases, the pretreatment step becomes more tedious and time-consuming. So developing a sensitive, rapid and high-throughput method for detection of COCs in human body is indispensable for law enforcement officers, treatment specialists and health officials. In this work, a new automated magnetic dispersive solid-phase extraction (MDSPE) sampling method followed by high performance liquid chromatography-mass spectrometry (HPLC-MS) was developed for quantitative enrichment of COCs from human urine, using prepared magnetic nanoparticles as absorbants. The nanoparticles were prepared by silanizing magnetic Fe3O4 nanoparticles and modifying them with divinyl benzene and vinyl pyrrolidone, which possesses the ability for specific adsorption of COCs. And this kind of magnetic particle facilitated the pretreatment steps by electromagnetically controlled extraction to achieve full automation. The proposed device significantly improved the sampling preparation efficiency with 32 samples in one batch within 40mins. Optimization of the preparation procedure for the magnetic nanoparticles was explored and the performances of magnetic nanoparticles were characterized by scanning electron microscopy, vibrating sample magnetometer and infrared spectra measurements. Several analytical experimental parameters were studied, including amount of particles, adsorption time, elution solvent, extraction and desorption kinetics, and the verification of the proposed method was accomplished. The limits of detection for the cocaine and cocaine metabolites were 0.09-1.1 ng·mL-1 with recoveries ranging from 75.1 to 105.7%. Compared to traditional sampling method, this method is time-saving and environmentally friendly. It was confirmed that the proposed automated method was a kind of highly effective way for the trace cocaine and cocaine metabolites analyses in human urine.

Keywords: automatic magnetic dispersive solid-phase extraction, cocaine detection, magnetic nanoparticles, urine sample testing

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2185 Effect of Z-VAD-FMK on in Vitro Viability of Dog Follicles

Authors: Leda Maria Costa Pereira, Maria Denise Lopes, Nucharin Songsasen

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Mammalian ovaries contain thousands of follicles that eventually degenerate or die after culture in vitro. Caspase-3 is a key enzyme that regulating cell death. Our objective was to examine the influence of anti-apoptotic drug Z-VAD-FMK (pan-caspase inhibitor) on in vitro viability of dog follicles within the ovarian cortex. Ovaries were obtained from prepubertal (age, 2.5–6 months) and adult (age, 8 months to 2 years) bitches and ovarian cortical fragments were recovered. The cortices were then incubated on 1.5% (w/v) agarose gel blocks within a 24-wells culture plate (three cortical pieces/well) containing Minimum Essential Medium Eagle - Alpha Modification (Alpha MEM) supplemented with 4.2 µg/ml insulin, 3.8 µg/ml transferrin, 5 ng/ml selenium, 2 mM L-glutamine, 100 µg/mL of penicillin G sodium, 100 µg/mL of streptomycin sulfate, 0.05 mM ascorbic acid, 10 ng/mL of FSH and 0.1% (w/v) polyvinyl alcohol in humidified atmosphere of 5% CO2 and 5% O2. The cortices were divided in six treatment groups: 1) 10 ng/mL EGF (EGF V0); 2) 10 ng/mL of EGF plus 1 mM Z-VAD-FMK (EGF V1); 3) 10 ng/mL of EGF and 10 mM Z-VAD-FMK (EGF V10); 4) 1 mM Z-VAD-FMK; 5) 10 mM Z-VAD-FMK and (6) no EGF and Z-VAD-FMK supplementation. Ovarian follicles within the tissues were processed for histology and assessed for follicle density, viability (based on morphology) and diameter immediately after collection (Control) or after 3 or 7 days of in vitro incubation. Comparison among fresh and culture treatment group was performed using ANOVA test. There were no differences (P > 0.05) in follicle density and viability among different culture treatments. However, there were differences in this parameter between culture days. Specifically, culturing tissue for 7 days resulted in significant reduction in follicle viability and density, regardless of treatments. We found a difference in size between culture days when these follicles were cultured using 10 mM Z-VAD-FMK or 10 ng/mL EGF (EGF V0). In sum, the finding demonstrated that Z-VAD-FMK at the dosage used in the present study does not provide the protective effect to ovarian tissue during in vitro culture. Future studies should explore different Z-VAD-FMK dosages or other anti-apoptotic agent, such as surviving in protecting ovarian follicles against cell death.

Keywords: anti apoptotic drug, bitches, follicles, Z-VAD-FMK

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2184 Comparison of Analgesic Efficacy of Paracetamol and Tramadol for Pain Relief in Active Labor

Authors: Krishna Dahiya

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Introduction: Labour pain has been described as the most severe pain experienced by women in their lives. Pain management in labour is one of the most important challenges faced by the obstetrician. The opioids are the primary treatment for patients with moderate and severe pain but these drugs are not always tolerated and are associated with dose-dependent side effects. Nonsteroidal anti-inflammatory drugs, too, are associated with variable adverse effects. Considering these factors, our study compared the efficacy and side effect of intravenous tramadol and paracetamol. Objective: To evaluate the efficacy and adverse effects of an intravenous infusion of 1000 mg of paracetamol as compared with an intravenous injection of 50mg of tramadol for intrapartum analgesia. Methods: In a randomized prospective study at Pt. BDS PGIMS, 200 women in active labor were allocated to received either paracetamol (n=100) or tramadol (n=100). The primary outcome was the efficacy of the drug to supply adequate analgesia as measured by a change in the visual analog scale (VAS) pain intensity score at various times after drug administration. The secondary outcomes included the need for additional rescue analgesia and the presence of adverse maternal or fetal events. Results: The mean age of cases were 25.55 ± 3.849 years and 25.60 ± 3.655 years respectively As recorded by the VAS score, there was significant pain reduction at 30 minutes, and at 1 and 2 hours in both groups (P<0.01). In comparison, between group I and II, a significantly higher rate of nausea and vomiting in tramadol group (14% vs 8%; P < 0.03) patients. Similarly, drowsiness (0% vs 11%; P<0.01), dry mouth (0% vs 8%; P<0.04) and dizziness (0% vs 9%; P<0.02) was also significant in group II. Conclusion: Due to difficulty in administering epidural analgesia to all parturients, administration of paracetamol and tramadol infusion for analgesia is simple and less invasive alternative. In the present study, both paracetamol and tramadol were equally effective for labour analgesia but paracetamol has emerged as safe alternative as compared to tramadol due to a low incidence of side effects.

Keywords: paracetamol, tramadol, labor, analgesia

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2183 Emergence of Ciprofloxacin Intermediate Susceptible Salmonella Typhi in India

Authors: Meenakshi Chaudhary, V .S. Randhawa, M. Jais, R. Dutta

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Introduction: An outbreak of Multi drug resistant S. Typhi (i.e. resistance to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) occurred in 1990's in India which peaked in 1992-93 and resulted in the change of drug of choice from chloramphenicol to ciprofloxacin for enteric fever. Currently an emergence of Ciprofloxacin susceptible S. Typhi isolates in the region is being reported which appears to be chromosomally mediated. Methodology: Six hundred sixty four strains were randomly selected from the time period between January 2008-December 2011 at the National Salmonella Phage Typing Centre, LHMC, New Delhi. The strains were representative of the north, central and south zones of India. All isolates were subjected to serotyping, biotyping, phage typing and then to antimicrobial susceptibility testing by CLSI disk diffusion (CLSI) technique to Ciprofloxacin, Cefotaxime, Ampicillin, Chloramphenicol, Trimethoprim-Sulfomethoxazole and Tetracycline. Subsequently MIC of the isolates was determined by E-test (AB-Biodisc). Results: More than 80% of the tested strains had intermediate susceptibility to ciprofloxacin. The E test revealed the MIC (Ciprofloxacin) of these strains to be in the range of 0.12 to 0.5 µg/ml. Sixty nine percent of ciprofloxacin intermediate susceptible strains belonged to Phage type E1 and fourteen percent of these were Vi- Negative i.e these could not be typed by the phage typing scheme of Craigie and Yen. All the strains remained susceptible to cefotaxime. Conclusion: Predominant isolation of intermediate susceptible S. Typhi strains from India would alter the recommendations of empiric treatment of enteric fever in the region. Alternative to the low cost ciprofloxacin will have to be sought or increased dosage and/or duration of ciprofloxacin will have to be recommended. The reasons for the trend of increase in percentage of intermediate susceptible S. Typhi strains are not clear but may be attributed partly to the revision of CLSI guidelines in 2013.

Keywords: salmonella typhi, decreased ciprofloxacin susceptibility, ciprofloxacin, minimum inhibitory concentration

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2182 Screening of Selected Medicinal Plants from Jordan for Their Protective Properties against Oxidative DNA Damage and Mutagenecity

Authors: Karem H. Alzoubi, Ahmad S. Alkofahi, Omar F. Khabour, Nizar M. Mhaidat

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Herbal medicinal products represent a major focus for drug development and industry and it holds a significant share in drug-market all over the globe. In here, selected medicinal plant extracts from Jordan with high antioxidative capacity were tested for their protective effect against oxidative DNA damage using in vitro 8-hydroxydeoxyguanisine and sister chromatid exchanges (SCEs) assays in cultured human lymphocytes. The following plant extracts were tested Cupressus sempervirens L., Psidium guajava (L.) Gaerth., Silybum marianum L., Malva sylvestris L., Varthemia iphionoides Boiss., Eminium spiculatum L. Blume, Pistachia palaestina Boiss., Artemisia herba-alba Asso, Ficus carica L., Morus alba Linn , Cucumis sativus L., Eucalyptus camaldulensis Dehnh., Salvia triloba L., Zizyphus spina-christi L. Desf., and Laurus nobilis L. A fractionation scheme for the active plant extracts of the above was followed. Plants extract fractions with best protective properties against DNA damage included hexane fraction of S. marianum L. (aerial parts), chloroform fractions of P. palaestina Boiss. (Fruits), ethanolic fractions of E. camaldulensis Dehnh (leaves), S. triloba L. (leaves), and ethanolic fractions of Z. spina-christi L. Desf. (Fruits/leaves). On the other hand, the ethanolic extracts of V. iphionoides Boiss was found to increase oxidative DNA damage. Results of the SCEs are undergoing. In conclusion, plant extracts with antioxidative DNA damage properties might have clinical applications in cancer prevention.

Keywords: medicinal plants extract, fractionation, oxidative DNA damage, 8-hydroxydeoxyguanisine, SCEs, Jordan

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2181 In Silico Exploration of Quinazoline Derivatives as EGFR Inhibitors for Lung Cancer: A Multi-Modal Approach Integrating QSAR-3D, ADMET, Molecular Docking, and Molecular Dynamics Analyses

Authors: Mohamed Moussaoui

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A series of thirty-one potential inhibitors targeting the epidermal growth factor receptor kinase (EGFR), derived from quinazoline, underwent 3D-QSAR analysis using CoMFA and CoMSIA methodologies. The training and test sets of quinazoline derivatives were utilized to construct and validate the QSAR models, respectively, with dataset alignment performed using the lowest energy conformer of the most active compound. The best-performing CoMFA and CoMSIA models demonstrated impressive determination coefficients, with R² values of 0.981 and 0.978, respectively, and Leave One Out cross-validation determination coefficients, Q², of 0.645 and 0.729, respectively. Furthermore, external validation using a test set of five compounds yielded predicted determination coefficients, R² test, of 0.929 and 0.909 for CoMFA and CoMSIA, respectively. Building upon these promising results, eighteen new compounds were designed and assessed for drug likeness and ADMET properties through in silico methods. Additionally, molecular docking studies were conducted to elucidate the binding interactions between the selected compounds and the enzyme. Detailed molecular dynamics simulations were performed to analyze the stability, conformational changes, and binding interactions of the quinazoline derivatives with the EGFR kinase. These simulations provided deeper insights into the dynamic behavior of the compounds within the active site. This comprehensive analysis enhances the understanding of quinazoline derivatives as potential anti-cancer agents and provides valuable insights for lead optimization in the early stages of drug discovery, particularly for developing highly potent anticancer therapeutics

Keywords: 3D-QSAR, CoMFA, CoMSIA, ADMET, molecular docking, quinazoline, molecular dynamic, egfr inhibitors, lung cancer, anticancer

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2180 Silymarin Reverses Scopolamine-Induced Memory Deficit in Object Recognition Test in Rats: A Behavioral, Biochemical, Histopathological and Immunohistochemical Study

Authors: Salma A. El-Marasy, Reham M. Abd-Elsalam, Omar A. Ahmed-Farid

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Dementia is characterized by impairments in memory and other cognitive abilities. This study aims to elucidate the possible ameliorative effect of silymarin on scopolamine-induced dementia using the object recognition test (ORT). The study was extended to demonstrate the role of cholinergic activity, oxidative stress, neuroinflammation, brain neurotransmitters and histopathological changes in the anti-amnestic effect of silymarin in demented rats. Wistar rats were pretreated with silymarin (200, 400, 800 mg/kg) or donepezil (10 mg/kg) orally for 14 consecutive days. Dementia was induced after the last drug administration by a single intraperitoneal dose of scopolamine (16 mg/kg). Then behavioral, biochemical, histopathological, and immunohistochemical analyses were then performed. Rats pretreated with silymarin counteracted scopolamine-induced non-spatial working memory impairment in the ORT and decreased acetylcholinesterase (AChE) activity, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), restored gamma-aminobutyric acid (GABA) and dopamine (DA) contents in the cortical and hippocampal brain homogenates. Silymarin dose-dependently reversed scopolamine-induced histopathological changes. Immunohistochemical analysis showed that silymarin dose-dependently mitigated protein expression of a glial fibrillary acidic protein (GFAP) and nuclear factor kappa-B (NF-κB) in the brain cortex and hippocampus. All these effects of silymarin were similar to that of the standard anti-amnestic drug, donepezil. This study reveals that the ameliorative effect of silymarin on scopolamine-induced dementia in rats using the ORT maybe in part mediated by, enhancement of cholinergic activity, anti-oxidant and anti-inflammatory activities as well as mitigation in brain neurotransmitters and histopathological changes.

Keywords: dementia, donepezil, object recognition test, rats, silymarin, scopolamine

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2179 Evaluation of Naringenin Role in Inhibiton of Lung Tumor Progression in Mice

Authors: Vishnu Varthan Vaithiyalingamjagannathan, M. N. Sathishkumar, K. S. Lakhsmi, D. Satheeshkumar, Srividyaammayappanrajam

Abstract:

Background:Naringenin, aglycone flavonoid possess certain activities like anti-oxidant, anti-estrogenic, anti-diabetic, cardioprotective, anti-obesity,anti-inflammatory, hepatoprotective and also have anti-cancer characteristics like carcinogenic inactivation, cell cycle arrest, anti-proliferation, apoptosis, anti-angiogenesis and enhances anti-oxidant activity. Methodology:The inhibitory effect of Naringenin in lung tumor progression estimated with adenocarcinoma (A549) cell lines (in vitro) and C57BL/6 mice injected with 5 X 106A549 cell lines (in vivo) in a tri-dose manner (Naringenin 100mg/kg,150mg/kg, and 200mg/kg) compared with standard chemotherapy drug cisplatin (7mg/kg). Results:The results of the present study revealed a dose-dependent activity in Naringenin and combination with cisplatin at a higher dose which showed decreased tumor progression in mice. In vitro studies carried out for estimation of cell survival and Nitric Oxide (NO) level, shows dose dependent action of Naringenin with IC50 value of 42µg/ml. In vivo studies were carried out in C57BL/6 mice. Naringenin satisfied the condition of an anti-cancer molecule with its characteristics in fragmentation assay, Zymography assay, anti-oxidant, and myeloperoxidase studies, than cisplatin which failed in anti-oxidant and myeloperoxidase effect. Both in vitro and in vivo establishes dose dependent decrease in NO levels. But whereas, Naringenin showed adverse results in Matrix Metalloproteinase (MMP) enzymatic levels with increase in dose levels. Conclusion:From the present study, Naringenin could suppress the lung tumor progression when given individually and also in combinatorial with standard chemotherapy drug.

Keywords: naringenin, in vitro, cell line, anticancer

Procedia PDF Downloads 435
2178 Natural Bio-Active Product from Marine Resources

Authors: S. Ahmed John

Abstract:

Marine forms-bacteria, actinobacteria, cynobacteria, fungi, microalgae, seaweeds mangroves and other halophytes an extremely important oceanic resources and constituting over 90% of the oceanic biomass. The marine natural products have lead to the discovery of many compounds considered worthy for clinical applications. The marine sources have the highest probability of yielding natural products. Natural derivatives play an important role to prevent the cancer incidences as synthetic drug transformation in mangrove. 28.12% of anticancer compound extracted from the mangroves. Exchocaria agollocha has the anti cancer compounds. The present investigation reveals the potential of the Exchocaria agollocha with biotechnological applications for anti cancer, antimicrobial drug discovery, environmental remediation, and developing new resources for the industrial process. The anti-cancer activity of Exchocaria agollocha was screened from 3.906 to 1000 µg/ml of concentration with the dilution leads to 1:1 to 1:128 following methanol and chloroform extracts. The cell viability in the Exchocaria agollocha was maximum at the lower concentration where as low at the higher concentration of methanol and chloroform extracts when compare to control. At 3.906 concentration, 85.32 and 81.96 of cell viability was found at 1:128 dilution of methanol and chloroform extracts respectively. At the concentration of 31.25 following 1:16 dilution, the cell viability was 65.55 in methanol and 45.55 in chloroform extracts. However, at the higher concentration, the cell viability 22.35 and 8.12 was recorded in the extracts of methanol and chloroform. The cell viability was more in methanol when compare to chloroform extracts at lower concentration. The present findings gives current trends in screening and the activity analysis of metabolites from mangrove resources and to expose the models to bring a new sustain for tackling cancer. Bioactive compounds of Exchocaria agollocha have extensive use in treatment of many diseases and serve as a compound and templates for synthetic modification.

Keywords: bio-active product, compounds, natural products and microalgae

Procedia PDF Downloads 246
2177 Anti-Bacterial Activity Studies of Derivatives of 6β-Hydroxy Betunolic Acid against Selected Stains of Gram (+) and Gram (-) Bacteria

Authors: S. Jayasinghe, W. G. D. Wickramasingha, V. Karunaratne, D. N. Karunaratne, A. Ekanayake

Abstract:

Multi-drug resistant microbial pathogens are a serious global health problem, and hence, there is an urgent necessity for discovering new drug therapeutics. However, finding alternatives is a one of the biggest challenges faced by the global drug industry due to the spiraling high cost and serious side effects associated with modern medicine. On the other hand, plants and their secondary metabolites can be considered as good sources of scaffolds to provide structurally diverse bioactive compounds as potential therapeutic agents. 6β-hydroxy betunolic acid is a triterpenoid isolated from bark of Schumacheria castaneifolia which is an endemic plant to Sri Lanka which has shown antibacterial activity against both Staphylococcus aureus (ATCC 29213) and methicillin-resistant S. aureus with Minimum Inhibition Concentration (MIC) of 16 µg/ml. The objective of this study was to determine the anti-bacterial activity for the derivatives of 6β- hydroxy betunolic acid against standard strains of Staphylococcus aureus (ATCC 29213 and ATCC 25923), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 35218 and ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), carbepenemas produce Kebsiella pneumonia (ATCC BAA 1705) and carbepenemas non produce Kebsiella pneumonia (ATCC BAA 1706) and four stains of clinically isolated methicillin resistance S. aureus and Acinetobacter. Structural analogues of 6β-hydroxy betunolic acid were synthesized by modifying the carbonyl group at C-3 to obtain olefin and oxime, the hydroxyl group at C-6 position to a ketone, the carboxylic acid at C-17 to obtain amide and halo ester and the olefin group at C-20 position to obtain epoxide. Chemical structures of the synthesized analogues were confirmed with spectroscopic data and antibacterial activity was determined through broth micro dilution assay. Results revealed that 6β- hydroxy betunolic acid shows significant antibacterial activity only against the Gram positive strains and it was inactive against all the tested Gram negative strains for the tested concentration range. However, structural modifications into oxime and olefin at C-3, ketone at C-6 and epoxide at C-20 decreased its antibacterial activity against the gram positive organisms and it was totally lost with the both modifications at C-17 into amide and ester. These results concluded that the antibacterial activity of 6β- hydroxy betunolic acid and derivatives is predominantly depending on the cell wall difference of the bacteria and the presence of carboxylic acid at C-17 is highly important for the antibacterial activity against Gram positive organisms.

Keywords: antibacterial activity, 6β- hydroxy betunolic acid, broth micro dilution assay, structure activity relationship

Procedia PDF Downloads 126
2176 A Prospective Study on the Evaluation of Statins Usage on HbA1c Control among Type 2 Diabetes Mellitus in an Outpatients Setting

Authors: Mohamed A. Hammad, Dzul Azri Mohamed Noor, Syed Azhar Syed Sulaiman, Abeer Kharshid, Nor Azizah Aziz, Tarek M. Elsayed

Abstract:

Medication safety is always an issue. In 2015, the National Pharmaceutical Control Bureau released a statement requesting all statins manufacturers in Malaysia to include the risk of diabetes information in the drug information leaflet in response to United States Food and Drug Administration (U.S. FDA) report. However, the data regarding this warning label in Malaysia is limited, so there is still some uncertainty whether such risk can also be observed in the Malaysian population or not. The study aims to determine the effect of statins on HbA1c% in type 2 diabetic outpatients in endocrine clinics at Hospital Pulau Pinang between June 2015 and May 2016 in Malaysia. In a prospective cohort study, records of 400 type 2 diabetic patients (control group 104 patients not using statin and treatment group 296 patients using statin) were reviewed to identify demographic criteria and lab tests. The prevalence of glycemic control (Glycated hemoglobin, HbA1C ≤ 7% for patient < 65 years, and < 8% for patient ≥ 65 years) was estimated, according to American Diabetes Association guidelines 2015. The results were presented as descriptive statistics. From 296 patients with Type 2 diabetes using statins cohort with a mean age of 57.52 ± 12.2 years, only 81 (27.4%) cases had controlled glycemia, and 215 (72.6%) had uncontrolled glycemia, CI: 95% (6.3–11.1). While the control group 104 diabetic patients had a mean age 46.1 ± 18 years and distributed among 59 (56.7%) patients with controlled diabetes and 45 (43.3%) cases, had uncontrolled glycemia, CI: 95% (5.2–10.3). The relative risk (RR) of uncontrolled glycemia in diabetic patients used statins was 1.68, and the excessive relative risk (ERR) was 68%. The absolute risk (AR) was 29.3%, and the number needed to harm (NNH) was 4. Diabetic patients using statins have more risk of uncontrolled glycemia than the patients with Type 2 diabetes non-using statins.

Keywords: diabetes mellitus, HbA1c, Malaysia, outpatients, statin, type 2, uncontrolled glycemia

Procedia PDF Downloads 284
2175 Aspirin Loaded Poly-L-Lactic Acid Nanofibers and Their Potentials as Small Diameter Vascular Grafts

Authors: Mahboubeh Kabiri, Saba Aslani

Abstract:

Among various approaches used for the treatment of cardiovascular diseases, the occlusion of the small-diameter vascular graft (SDVG) is still an unresolved problem which seeks further research to address them. Though autografts are now the gold standards to be replaced for blocked coronary arteries, they suffer from inadequate quality and quantity. On the other hand, the major problems of the tissue engineered grafts are thrombosis and intimal hyperplasia. Provision of a suitable spatiotemporal release pattern of anticoagulant agents such as heparin and aspirin can be a step forward to overcome such issues . Herein, we fabricated electrospun scaffolds from FDA (Food and Drug Administration) approved poly-L-lactic acid (PLLA) with aspirin loaded into the nanofibers. Also, we surface coated the scaffolds with Amniotic Membrane lysate as a source for natural elastic polymers and a mimic of endothelial basement membrane. The scaffolds were characterized thoroughly structurally and mechanically for their morphology, fiber orientation, tensile strength, hydrophilicity, cytotoxicity, aspirin release and cell attachment support. According to the scanning electron microscopy (SEM) images, the size of fibers ranged from 250 to 500 nm. The scaffolds showed appropriate tensile strength expected for vascular grafts. Cellular attachment, growth, and infiltration were proved using SEM and MTT (3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide) assay. Drug-loaded scaffolds showed a sustained release profile of aspirin in 7 days. An enhanced cytocompatibility was observed in AM-coated electrospun PLLA fibers compared to uncoated scaffolds. Our results together indicated that AM lysate coated ASA releasing scaffolds have promising potentials for development of a biocompatible SDVG.

Keywords: vascular tissue engineering, vascular grafts, anticoagulant agent, aspirin, amniotic membrane

Procedia PDF Downloads 163
2174 Preparation and Properties of Chloroacetated Natural Rubber Rubber Foam Using Corn Starch as Curing Agent

Authors: Ploenpit Boochathum, Pitchayanad Kaolim, Phimjutha Srisangkaew

Abstract:

In general, rubber foam is produced based on the sulfur curing system. However, the remaining sulfur in the rubber product waste is burned to sulfur dioxide gas causing the environment pollution. To avoid using sulfur as curing agent in the rubber foam products, this research work proposes non-sulfur curing system by using corn starch as a curing agent. The ether crosslinks were proposed to be produced via the functional bonding between hydroxyl groups of the starch molecules and chloroacetate groups added on the natural rubber molecules. The chloroacetated natural rubber (CNR) latex was prepared via the epoxidation reaction of the concentrated natural rubber latex, subsequently, epoxy rings were attacked by chloroacetic acid to produce hydroxyl groups and chloroacetate groups on the rubber molecules. Foaming agent namely NaHCO3 was selected to add in the CNR latex due to the low decomposition temperature at about 50°C. The appropriate curing temperature was assigned to be 90°C that is above gelatinization temperature; 60-70°C, of starch. The effect of weight ratio of starch, i.e., 0 phr, 3 phr and 5 phr, on the physical properties of CNR rubber foam was investigated. It was found that density reduced from 0.81 g/cm3 for 0 phr to 0.75 g/cm3 for 3 phr and 0.79 g/cm3 for 5 phr. The ability to return to its original thickness after prolonged compressive stresses of CNR rubber foam cured with starch loading of 5 phr was found to be considerably better than that of CNR rubber foam cured with starch 3 phr and CNR rubber foam without addition of starch according to the compression set that was determined to decrease from 66.67% to 40% and 26.67% with the increase loading of starch. The mechanical properties including tensile strength and modulus of CNR rubber foams cured using starch were determined to increase except that the elongation at break was found to decrease. In addition, all mechanical properties of CNR rubber foams cured with the starch 3 phr and 5 phr were found to be slightly different and drastically higher than those of CNR rubber foam without the addition of starch. This research work indicates that starch can be applicable as a curing agent for CNR rubber. This is confirmed by the increase of the elastic modulus (G') of CNR rubber foams that was cured with the starch over the CNR rubber foam without curing agent. This type of rubber foam is believed to be one of the biodegradable and environment-friendly product that can be cured at low temperature of 90°C.

Keywords: chloroacetated natural rubber, corn starch, non-sulfur curing system, rubber foam

Procedia PDF Downloads 319
2173 An Experimental Investigation on Explosive Phase Change of Liquefied Propane During a Bleve Event

Authors: Frederic Heymes, Michael Albrecht Birk, Roland Eyssette

Abstract:

Boiling Liquid Expanding Vapor Explosion (BLEVE) has been a well know industrial accident for over 6 decades now, and yet it is still poorly predicted and avoided. BLEVE is created when a vessel containing a pressure liquefied gas (PLG) is engulfed in a fire until the tank rupture. At this time, the pressure drops suddenly, leading the liquid to be in a superheated state. The vapor expansion and the violent boiling of the liquid produce several shock waves. This works aimed at understanding the contribution of vapor ad liquid phases in the overpressure generation in the near field. An experimental work was undertaken at a small scale to reproduce realistic BLEVE explosions. Key parameters were controlled through the experiments, such as failure pressure, fluid mass in the vessel, and weakened length of the vessel. Thirty-four propane BLEVEs were then performed to collect data on scenarios similar to common industrial cases. The aerial overpressure was recorded all around the vessel, and also the internal pressure changed during the explosion and ground loading under the vessel. Several high-speed cameras were used to see the vessel explosion and the blast creation by shadowgraph. Results highlight how the pressure field is anisotropic around the cylindrical vessel and highlights a strong dependency between vapor content and maximum overpressure from the lead shock. The time chronology of events reveals that the vapor phase is the main contributor to the aerial overpressure peak. A prediction model is built upon this assumption. Secondary flow patterns are observed after the lead. A theory on how the second shock observed in experiments forms is exposed thanks to an analogy with numerical simulation. The phase change dynamics are also discussed thanks to a window in the vessel. Ground loading measurements are finally presented and discussed to give insight into the order of magnitude of the force.

Keywords: phase change, superheated state, explosion, vapor expansion, blast, shock wave, pressure liquefied gas

Procedia PDF Downloads 77
2172 Relevance of Dosing Time for Everolimus Toxicity in Respect to the Circadian P-Glycoprotein Expression in Mdr1a::Luc Mice

Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

Abstract:

P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

Procedia PDF Downloads 342
2171 Optimizing the Location of Parking Areas Adapted for Dangerous Goods in the European Road Transport Network

Authors: María Dolores Caro, Eugenio M. Fedriani, Ángel F. Tenorio

Abstract:

The transportation of dangerous goods by lorries throughout Europe must be done by using the roads conforming the European Road Transport Network. In this network, there are several parking areas where lorry drivers can park to rest according to the regulations. According to the "European Agreement concerning the International Carriage of Dangerous Goods by Road", parking areas where lorries transporting dangerous goods can park to rest, must follow several security stipulations to keep safe the rest of road users. At this respect, these lorries must be parked in adapted areas with strict and permanent surveillance measures. Moreover, drivers must satisfy several restrictions about resting and driving time. Under these facts, one may expect that there exist enough parking areas for the transport of this type of goods in order to obey the regulations prescribed by the European Union and its member countries. However, the already-existing parking areas are not sufficient to cover all the stops required by drivers transporting dangerous goods. Our main goal is, starting from the already-existing parking areas and the loading-and-unloading location, to provide an optimal answer to the following question: how many additional parking areas must be built and where must they be located to assure that lorry drivers can transport dangerous goods following all the stipulations about security and safety for their stops? The sense of the word “optimal” is due to the fact that we give a global solution for the location of parking areas throughout the whole European Road Transport Network, adjusting the number of additional areas to be as lower as possible. To do so, we have modeled the problem using graph theory since we are working with a road network. As nodes, we have considered the locations of each already-existing parking area, each loading-and-unloading area each road bifurcation. Each road connecting two nodes is considered as an edge in the graph whose weight corresponds to the distance between both nodes in the edge. By applying a new efficient algorithm, we have found the additional nodes for the network representing the new parking areas adapted for dangerous goods, under the fact that the distance between two parking areas must be less than or equal to 400 km.

Keywords: trans-european transport network, dangerous goods, parking areas, graph-based modeling

Procedia PDF Downloads 280
2170 Ultracapacitor State-of-Energy Monitoring System with On-Line Parameter Identification

Authors: N. Reichbach, A. Kuperman

Abstract:

The paper describes a design of a monitoring system for super capacitor packs in propulsion systems, allowing determining the instantaneous energy capacity under power loading. The system contains real-time recursive-least-squares identification mechanism, estimating the values of pack capacitance and equivalent series resistance. These values are required for accurate calculation of the state-of-energy.

Keywords: real-time monitoring, RLS identification algorithm, state-of-energy, super capacitor

Procedia PDF Downloads 535
2169 Numerical Simulation of Precast Concrete Panels for Airfield Pavement

Authors: Josef Novák, Alena Kohoutková, Vladimír Křístek, Jan Vodička

Abstract:

Numerical analysis software belong to the main tools for simulating the real behavior of various concrete structures and elements. In comparison with experimental tests, they offer an affordable way to study the mechanical behavior of structures under various conditions. The contribution deals with a precast element of an innovative airfield pavement system which is being developed within an ongoing scientific project. The proposed system consists a two-layer surface course of precast concrete panels positioned on a two-layer base of fiber-reinforced concrete with recycled aggregate. As the panels are supposed to be installed directly on the hardened base course, imperfections at the interface between the base course and surface course are expected. Considering such circumstances, three various behavior patterns could be established and considered when designing the precast element. Enormous costs of full-scale experiments force to simulate the behavior of the element in a numerical analysis software using finite element method. The simulation was conducted on a nonlinear model in order to obtain such results which could fully compensate results from the experiments. First, several loading schemes were considered with the aim to observe the critical one which was used for the simulation later on. The main objective of the simulation was to optimize reinforcement of the element subject to quasi-static loading from airplanes. When running the simulation several parameters were considered. Namely, it concerns geometrical imperfections, manufacturing imperfections, stress state in reinforcement, stress state in concrete and crack width. The numerical simulation revealed that the precast element should be heavily reinforced to fulfill all the demands assumed. The main cause of using high amount of reinforcement is the size of the imperfections which could occur at real structure. Improving manufacturing quality, the installation of the precast panels on a fresh base course or using a bedding layer underneath the surface course belong to the main steps how to reduce the size of imperfections and consequently lower the consumption of reinforcement.

Keywords: nonlinear analysis, numerical simulation, precast concrete, pavement

Procedia PDF Downloads 256
2168 Simulation of Scaled Model of Tall Multistory Structure: Raft Foundation for Experimental and Numerical Dynamic Studies

Authors: Omar Qaftan

Abstract:

Earthquakes can cause tremendous loss of human life and can result in severe damage to a several of civil engineering structures especially the tall buildings. The response of a multistory structure subjected to earthquake loading is a complex task, and it requires to be studied by physical and numerical modelling. For many circumstances, the scale models on shaking table may be a more economical option than the similar full-scale tests. A shaking table apparatus is a powerful tool that offers a possibility of understanding the actual behaviour of structural systems under earthquake loading. It is required to use a set of scaling relations to predict the behaviour of the full-scale structure. Selecting the scale factors is the most important steps in the simulation of the prototype into the scaled model. In this paper, the principles of scaling modelling procedure are explained in details, and the simulation of scaled multi-storey concrete structure for dynamic studies is investigated. A procedure for a complete dynamic simulation analysis is investigated experimentally and numerically with a scale factor of 1/50. The frequency domain accounting and lateral displacement for both numerical and experimental scaled models are determined. The procedure allows accounting for the actual dynamic behave of actual size porotype structure and scaled model. The procedure is adapted to determine the effects of the tall multi-storey structure on a raft foundation. Four generated accelerograms were used as inputs for the time history motions which are in complying with EC8. The output results of experimental works expressed regarding displacements and accelerations are compared with those obtained from a conventional fixed-base numerical model. Four-time history was applied in both experimental and numerical models, and they concluded that the experimental has an acceptable output accuracy in compare with the numerical model output. Therefore this modelling methodology is valid and qualified for different shaking table experiments tests.

Keywords: structure, raft, soil, interaction

Procedia PDF Downloads 136
2167 The Effectiveness of Copegus (Ribavirin) Placed in a Field of Unexplored Properties of Low-Level Laser Radiation in the Treatment of Long-Covid Syndrome

Authors: Naylya Djumaeva

Abstract:

Since the end of 2019, the world has been shaken by an infection that has claimed the lives of more than six and a half million patients. Currently, SARS-CoV-2 not only causes acute damage but has long-term consequences affecting every organ and has brought a wave of a new chronic disabling condition called Long-Covid..This preliminary study describes an application of un-explored properties of low-level laser radiation with laser- light emitter in the field of which is placed Copegus (Ribavirin) with the aim of treatment of patients with Long-Covid syndrome. The difference from the traditional use of the drug is that Copegus was not prescribed to the patient by the traditional method - orally or intravenously, and the medicinal properties of the drug were introduced into the patient’s body using the un-explored properties of low-power laser radiation. Ninety eight patients with Long- Covid syndrome were observed. The obtained findings suggest that under the influence of the field formed into the laser- light emitter with a Copegus placed inside the field, the remote transfer of pharmacological properties of Сopegus occurs. Conclusions about the produced effect of exposure were made based on improvement in the condition of patients, the disappearance of complaints, and positive changes in various diagnostic tests performed by the patients. Biography: Djumaeva N completed her PhD from the Institute of Epidemiology, Microbiology and Infectious Diseases in 2000. In her dissertation work devoted to the treatment of patients with chronic hepatitis B virus infection, she presented data on the possible influence of Complex Homeopathic Preparations on the organization of bound intracellular water in the cells of the body. She is the Consultant (Neurologist) at the Scientific-Research Institute for Virology, Uzbekistan, and an expert in “medicament testing” method (30 years). She has published 43 papers, including 2 patents.

Keywords: long covid, low level laser, copegus, laser- light emmiter

Procedia PDF Downloads 95
2166 Static Relaxation of Glass Fiber Reinforced Pipes

Authors: Mohammed Y. Abdellah, Mohamed K. Hassan, A. F. Mohamed, Shadi M. Munshi, A. M. Hashem

Abstract:

Pips made from glass fiber reinforced polymer has competitive role in petroleum industry. The need of evaluating the mechanical behavior of (GRP) pipes is essential objects. Stress relaxation illustrates how polymers relieve stress under constant strain. Static relaxation test is carried out at room temperature. The material gives poor static relaxation strength, two loading cycles have been observed for the tested specimen.

Keywords: GRP, sandwich composite material, static relaxation, stress relief

Procedia PDF Downloads 625
2165 Review and Analysis of Parkinson's Tremor Genesis Using Mathematical Model

Authors: Pawan Kumar Gupta, Sumana Ghosh

Abstract:

Parkinson's Disease (PD) is a long-term neurodegenerative movement disorder of the central nervous system with vast symptoms related to the motor system. The common symptoms of PD are tremor, rigidity, bradykinesia/akinesia, and postural instability, but the clinical symptom includes other motor and non‐motor issues. The motor symptoms of the disease are consequence of death of the neurons in a region of the midbrain known as substantia nigra pars compacta, leading to decreased level of a neurotransmitter known as dopamine. The cause of this neuron death is not clearly known but involves formation of Lewy bodies, an abnormal aggregation or clumping of the protein alpha-synuclein in the neurons. Unfortunately, there is no cure for PD, and the management of this disease is challenging. Therefore, it is critical for a patient to be diagnosed at early stages. A limited choice of drugs is available to improve the symptoms, but those become less and less effective over time. Apart from that, with rapid growth in the field of science and technology, other methods such as multi-area brain stimulation are used to treat patients. In order to develop advanced techniques and to support drug development for treating PD patients, an accurate mathematical model is needed to explain the underlying relationship of dopamine secretion in the brain with the hand tremors. There has been a lot of effort in the past few decades on modeling PD tremors and treatment effects from a computational point of view. These models can effectively save time as well as the cost of drug development for the pharmaceutical industry and be helpful for selecting appropriate treatment mechanisms among all possible options. In this review paper, an effort is made to investigate studies on PD modeling and analysis and to highlight some of the key advances in the field over the past centuries with discussion on the current challenges.

Keywords: Parkinson's disease, deep brain stimulation, tremor, modeling

Procedia PDF Downloads 140