Search results for: drug carrier

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

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

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

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

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

Keywords: itraconazole, gender, hydroxyitraconazole, pharmacokinetics

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

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

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

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Authors: C. N. Okafor, M. Maaza, T. A. E. Mokrani

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A proton exchange membrane has been developed for Direct Methanol Fuel Cell (DMFC). The nanofiber network composite membranes were prepared by interconnected network of Nafion (perfuorosulfonic acid) nanofibers that have been embedded in an uncharged and inert polymer matrix, by electro-spinning. The spinning solution of Nafion with a low concentration (1 wt. % compared to Nafion) of high molecular weight poly(ethylene oxide), as a carrier polymer. The interconnected network of Nafion nanofibers with average fiber diameter in the range of 160-700nm, were used to make the membranes, with the nanofiber occupying up to 85% of the membrane volume. The matrix polymer was cross-linked with Norland Optical Adhesive 63 under UV. The resulting membranes showed proton conductivity of 0.10 S/cm at 25°C and 80% RH; and methanol permeability of 3.6 x 10-6 cm2/s.

Keywords: composite membrane, electrospinning, fuel cell, nanofibers

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Authors: Abbas Jafarizad, Duygu Ekinci

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In this work targeted drug delivery is proposed to decrease adverse effect of drugs with concomitant reduces in consumption and treatment outgoings. Nanoparticles (NPs) can be prepared from a variety of materials such as lipid, biodegradable polymer that prevent the drugs cytotoxicity in healthy cells, etc. One of the most important drugs used in chemotherapy is mitoxantrone (MTX) which prevents cell proliferation by inhibition of topoisomerase II and DNA repair; however, it is not selective and has some serious side effects. In this study, mentioned aim is achieved by using several nanocarriers like magnetite (Fe3O4) and their composites with magnetic graphene oxide (Fe3O4@GO). Also, cytotoxic potential of Fe3O4, Fe3O4-MTX, and Fe3O4@GO-MTX nanocomposite were evaluated on mesenchymal stem cells (MSCs). In this study, we reported the synthesis of monodisperse Fe3O4 NPs and Fe3O4@GO nanocomposite and their structures were investigated by using field emission scanning electron microscope (FESEM), Fourier transform infrared (FTIR) spectra, atomic force microscopy (AFM), Brauneur Emmet Teller (BET) isotherm and contact angle studies. Moreover, we used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to evaluate cytotoxic effects of MTX, Fe3O4 NPs, Fe3O4-MTX and Fe3O4@GO-MTX nanocomposite on MSCs. The in-vitro MTT results indicated that all concentrations of MTX and Fe3O4@GO-MTX nanocomposites showed cytotoxic effects while all concentrations of Fe3O4 NPs and Fe3O4-MTX NPs did not show any cytotoxic effect on stem cells. The results from this study indicated that using Fe3O4 NPs as anticancer drug delivery systems could be a trustworthy method for cancer treatment. But for reaching excellent and accurate results, further investigation is necessary.

Keywords: mitoxantrone, magnetite, magnetic graphene oxide, MTT assay, mesenchymal stem cells

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Authors: Nashed Atef Nashed Farag

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Introduction: Reporting adverse events following vaccination remains a challenge. WHO has mandated pharmacovigilance centers around the world to submit Adverse Events Following Immunization (AEFI) reports from different countries to a large electronic database of adverse drug event data called Vigibase. Despite sufficient information about AEFIs on Vigibase, they are not available to the general public. However, the WHO has an alternative website called VigiAccess, an open-access website that serves as an archive for reported adverse reactions and AEFIs. The aim of the study was to establish a reporting model for a number of commonly used vaccines in the VigiAccess system. Methods: On February 5, 2018, VigiAccess comprehensively searched for ESSI reports on the measles vaccine, oral polio vaccine (OPV), yellow fever vaccine, pneumococcal vaccine, rotavirus vaccine, meningococcal vaccine, tetanus vaccine, and tuberculosis vaccine (BCG). These are reports from all pharmacovigilance centers around the world since they joined the WHO Drug Monitoring Program. Results: After an extensive search, VigiAccess found 9,062 AEFIs from the measles vaccine, 185,829 AEFIs from the OPV vaccine, 24,577 AEFIs from the yellow fever vaccine, 317,208 AEFIs from the pneumococcal vaccine, 73,513 AEFIs from the rotavirus vaccine, and 145,447 AEFIs from meningococcal cal vaccine, 22,781 EI FI vaccines against tetanus and 35,556 BCG vaccines against AEFI. Conclusion: The study found that among the eight vaccines examined, pneumococcal vaccines were associated with the highest number of AEFIs, while measles vaccines were associated with the fewest AEFIs.

Keywords: surgical approach, anatomical approach, decompression, axillary nerve, quadrangular space adverse events following immunization, cameroon, COVID-19 vaccines, nOPV, ODK vaccines, adverse reactions, VigiAccess, adverse event reporting

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Authors: Semih Demir, Anil Celebi

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Circuit switched networks widely used until the end of the 20^th century have been transformed into packages switched networks. Time Division Multiplexing over Internet Protocol (TDMoIP) is a system that enables Time Division Multiplexing (TDM) traffic to be carried over packet switched networks (PSN). In TDMoIP systems, devices that send TDM data to the PSN and receive it from the network must operate with the same clock frequency. In this study, it was aimed to implement clock synchronization process in Field Programmable Gate Array (FPGA) chips using time information attached to the packages received from PSN. The designed hardware is verified using the datasets obtained for the different carrier types and comparing the results with the software model. Field tests are also performed by using the real time TDMoIP system.

Keywords: clock recovery on TDMoIP, FPGA, MATLAB reference model, clock synchronization

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Authors: Adela Diepoltova, Klara Konecna, Ondrej Jandourek, Petr Nachtigal

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A loss of control over antibiotic-resistant pathogens has become a global issue due to severe and often untreatable infections. This state is reflected in complicated treatment, health costs, and higher mortality. All these factors emphasize the urgent need for the discovery and development of new anti-infectives. One of the most common pathogens mentioned in the phenomenon of antibiotic resistance are bacteria of the genus Staphylococcus. These bacterial agents have developed several mechanisms against the effect of antibiotics. One of them is biofilm formation. In staphylococci, biofilms are associated with infections such as endocarditis, osteomyelitis, catheter-related bloodstream infections, etc. To author's best knowledge, no validated and standardized methodology evaluating candidate compound activity against staphylococcal biofilms exists. However, a variety of protocols for in vitro drug activity testing has been suggested, yet there are often fundamental differences. Based on our experience, a key methodological step that leads to credible results is to form a robust biofilm with appropriate attributes such as firm adherence to the substrate, a complex arrangement in layers, and the presence of extracellular polysaccharide matrix. At first, for the purpose of drug antibiofilm activity evaluation, the focus was put on various conditions (supplementation of cultivation media by human plasma/fetal bovine serum, shaking mode, the density of initial inoculum) that should lead to reproducible and robust in vitro staphylococcal biofilm formation in microtiter plate model. Three model staphylococcal reference strains were included in the study: Staphylococcus aureus (ATCC 29213), methicillin-resistant Staphylococcus aureus (ATCC 43300), and Staphylococcus epidermidis (ATCC 35983). The total biofilm biomass was quantified using the Christensen method with crystal violet, and results obtained from at least three independent experiments were statistically processed. Attention was also paid to the viability of the biofilm-forming staphylococcal cells and the presence of extracellular polysaccharide matrix. The conditions that led to robust biofilm biomass formation with attributes for biofilms mentioned above were then applied by introducing an alternative method analogous to the commercially available test system, the Calgary Biofilm Device. In this test system, biofilms are formed on pegs that are incorporated into the lid of the microtiter plate. This system provides several advantages (in situ detection and quantification of biofilm microbial cells that have retained their viability after drug exposure). Based on our preliminary studies, it was found that the attention to the peg surface and substrate on which the bacterial biofilms are formed should also be paid to. Therefore, further steps leading to the optimization were introduced. The surface of pegs was coated by human plasma, fetal bovine serum, and L-polylysine. Subsequently, the willingness of bacteria to adhere and form biofilm was monitored. In conclusion, suitable conditions were revealed, leading to the formation of reproducible, robust staphylococcal biofilms in vitro for the microtiter model and the system analogous to the Calgary biofilm device, as well. The robustness and typical slime texture could be detected visually. Likewise, an analysis by confocal laser scanning microscopy revealed a complex three-dimensional arrangement of biofilm forming organisms surrounded by an extracellular polysaccharide matrix.

Keywords: anti-biofilm drug activity screening, in vitro biofilm formation, microtiter plate model, the Calgary biofilm device, staphylococcal infections, substrate modification, surface coating

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Authors: Bongsu Choi, Tae-Ho Song

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Vacuum insulation panel (VIP) is a promising thermal insulator for buildings, refrigerator, LNG carrier and so on. In general, it has the thermal conductivity of 2~4 mW/m•K. However, this thermal conductivity is that measured at the center of VIP. The total effective thermal conductivity of VIP is larger than this value due to the edge conduction through the envelope. In this paper, the edge conduction of VIP is examined theoretically, numerically and experimentally. To confirm the existence of the edge conduction, numerical analysis is performed for simple two-dimensional VIP model and a theoretical model is proposed to calculate the edge conductivity. Also, the edge conductivity is measured using the vacuum guarded hot plate and the experiment is validated against numerical analysis. The results show that the edge conductivity is dependent on the width of panel and thickness of Al-foil. To reduce the edge conduction, it is recommended that the VIP should be made as big as possible or made of thin Al film envelope.

Keywords: envelope, edge conduction, thermal conductivity, vacuum insulation panel

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Authors: Kobauri Sophio, Kantaria Tengiz, Tugushi David, Puiggali Jordi, Katsarava Ramaz

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Biodegradable biomaterials (BB) are of high interest for numerous applications in modern medicine as resorbable surgical materials and drug delivery systems. This kind of materials can be cleared from the body after the fulfillment of their function that excludes a surgical intervention for their removal. One of the most promising BBare amino acids based biodegradable poly(ester amide)s (PEAs) which are composed of naturally occurring (α-amino acids) and non-toxic building blocks such as fatty diols and dicarboxylic acids. Key bis-nucleophilic monomers for synthesizing the PEAs are diamine-diesters-di-p-toluenesulfonic acid salts of bis-(α-amino acid)-alkylenediesters (TAADs) which form the PEAs after step-growth polymerization (polycondensation) with bis-electrophilic counter-partners - activated diesters of dicarboxylic acids. The PEAs combine all advantages of the 'parent polymers' – polyesters (PEs) and polyamides (PAs): Ability of biodegradation (PEs), a high affinity with tissues and a wide range of desired mechanical properties (PAs). The scopes of applications of thePEAs can substantially be expanded by their functionalization, e.g. through the incorporation of hydrophobic fragments into the polymeric backbones. Hydrophobically modified PEAs can form non-covalent adducts with various compounds that make them attractive as drug carriers. For hydrophobic modification of the PEAs, we selected so-called 'Azlactone Method' based on the application of p-phenylene-bis-oxazolinons (bis-azlactones, BALs) as active bis-electrophilic monomers in step-growth polymerization with TAADs. Interaction of BALs with TAADs resulted in the PEAs with low MWs (Mw2,800-19,600 Da) and poor material properties. The high-molecular-weight PEAs (Mw up to 100,000) with desirable material properties were synthesized after replacement of a part of BALs with activated diester - di-p-nitrophenylsebacate, or a part of TAAD with alkylenediamine – 1,6-hexamethylenediamine. The new hydrophobically modified PEAs were characterized by FTIR, NMR, GPC, and DSC. It was shown that after the hydrophobic modification the PEAs retain the biodegradability (in vitro study catalyzed by α-chymptrypsin and lipase), and are of interest for constructing resorbable surgical and pharmaceutical devices including drug delivering containers such as microspheres. The new PEAs are insoluble in hydrophobic organic solvents such as chloroform or dichloromethane (swell only) that allowed elaborating a new technology of fabricating microspheres.

Keywords: amino acids, biodegradable polymers, bis-azlactones, microspheres

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Authors: Veronika Lesáková, Silvia Slezáková, František Štěpánek

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Additive manufacturing technologies producing drug dosage forms aimed at personalized medicine applications are promising strategies with several advantages over the conventional production methods. One of the emerging technologies is 3D printing which reduces manufacturing steps and thus allows a significant drop in expenses. A decrease in material consumption is also a highly impactful benefit as the tested drugs are frequently expensive substances. In addition, 3D printed dosage forms enable increased patient compliance and prevent misdosing as the dosage forms are carefully designed according to the patient’s needs. The incorporation of multiple drugs into a single dosage form further increases the degree of personalization. Our research focuses on the development of 3D printed tablets incorporating multiple drugs (candesartan, losartan) and thermoplastic polymers (e.g., KlucelTM HPC EF). The filaments, an essential feed material for 3D printing,wereproduced via hot-melt extrusion. Subsequently, the extruded filaments of various formulations were 3D printed into tablets using an FDM 3D printer. Then, we have assessed the influence of the internal structure of 3D printed tablets and formulation on dissolution behaviour by obtaining the dissolution profiles of drugs present in the 3D printed tablets. In conclusion, we have developed tablets containing multiple drugs providing modified release profiles. The 3D printing experiments demonstrate the high tunability of 3D printing as each tablet compartment is constructed with a different formulation. Overall, the results suggest that the 3D printing technology is a promising manufacturing approach to dual tablet preparation for personalized medicine.

Keywords: 3D printing, drug delivery, hot-melt extrusion, dissolution kinetics

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Authors: Bao-Fang Wen, Meng-Na Dai, Gao-Pei Zhu, Chen-Xi Zhang, Jing Sun, Xun-Bao Yin, Yu-Han Zhao, Hong-Wei Sun, Wei-Fen Zhang

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A drug-loaded nanoparticles containing berberine hydrochloride (BH/FA-CTS-NPs) was prepared. The physicochemical characterizations of BH/FA-CTS-NPs and the inhibitory effect on the HeLa cells were investigated. Folic acid-conjugated chitosan (FA-CTS) was prepared by amino reaction of folic acid active ester and chitosan molecules; BH/FA-CTS-NPs were prepared using ionic cross-linking technique with BH as a model drug. The morphology and particle size were determined by Transmission Electron Microscope (TEM). The average diameters and polydispersity index (PDI) were evaluated by Dynamic Light Scattering (DLS). The interaction between various components and the nanocomplex were characterized by Fourier Transform Infrared Spectroscopy (FT-IR). The entrapment efficiency (EE), drug-loading (DL) and in vitro release were studied by UV spectrophotometer. The effect of cell anti-migratory and anti-invasive actions of BH/FA-CTS-NPs were investigated using MTT assays, wound healing assays, Annexin-V-FITC single staining assays, and flow cytometry, respectively. HeLa nude mice subcutaneously transplanted tumor model was established and treated with different drugs to observe the effect of BH/FA-CTS-NPs in vivo on HeLa bearing tumor. The BH/FA-CTS-NPs prepared in this experiment have a regular shape, uniform particle size, and no aggregation phenomenon. The results of DLS showed that mean particle size, PDI and Zeta potential of BH/FA-CTS NPs were (249.2 ± 3.6) nm, 0.129 ± 0.09, 33.6 ± 2.09, respectively, and the average diameter and PDI were stable in 90 days. The results of FT-IR demonstrated that the characteristic peaks of FA-CTS and BH/FA-CTS-NPs confirmed that FA-CTS cross-linked successfully and BH was encapsulated in NPs. The EE and DL amount were (79.3 ± 3.12) % and (7.24 ± 1.41) %, respectively. The results of in vitro release study indicated that the cumulative release of BH/FA-CTS NPs was (89.48±2.81) % in phosphate-buffered saline (PBS, pH 7.4) within 48h; these results by MTT assays and wund healing assays indicated that BH/FA-CTS NPs not only inhibited the proliferation of HeLa cells in a concentration and time-dependent manner but can induce apoptosis as well. The subcutaneous xenograft tumor formation rate of human cervical cancer cell line HeLa in nude mice was 98% after inoculation for 2 weeks. Compared with BH group and BH/CTS-NPs group, the xenograft tumor growth of BH/FA-CTS-NPs group was obviously slower; the result indicated that BH/FA-CTS-NPs could significantly inhibit the growth of HeLa xenograft tumor. BH/FA-CTS NPs with the sustained release effect could be prepared successfully by the ionic crosslinking method. Considering these properties, block proliferation and impairing the migration of the HeLa cell line, BH/FA-CTS NPs could be an important compound for consideration in the treatment of cervical cancer.

Keywords: folic-acid, chitosan, berberine hydrochloride, nanoparticles, cervical cancer

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Authors: Irtaza M. Syed, Kaamran Raahemifar

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This paper presents a model predictive control (MPC) of a utility interactive (UI) single phase inverter (SPI) for a photovoltaic (PV) system at residential/distribution level. The proposed model uses single-phase phase locked loop (PLL) to synchronize SPI with the grid and performs MPC control in a dq reference frame. SPI model consists of boost converter (BC), maximum power point tracking (MPPT) control, and a full bridge (FB) voltage source inverter (VSI). No PI regulators to tune and carrier and modulating waves are required to produce switching sequence. Instead, the operational model of VSI is used to synthesize sinusoidal current and track the reference. Model is validated using a three kW PV system at the input of UI-SPI in Matlab/Simulink. Implementation and results demonstrate simplicity and accuracy, as well as reliability of the model.

Keywords: phase locked loop, voltage source inverter, single phase inverter, model predictive control, Matlab/Simulink

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Authors: Shweta Verma

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Background: Epilepsy is a chronic non-communicable central nervous system (CNS) disorder which affects a large population of all ages. Different classes of drugs are used for the treatment of this neurological disorder, but due to augmented drug resistance and side effects, these drugs become incompetent. Therefore, we design the synthesis of ten new derivatives of Phenytoin. The moiety of Phenytoin was hybridized with different phenols by using three step approach. The synthesized molecules were then investigated for different physicochemical parameters, such as Log P values using diverse software programs and to predict the potential to cross the blood-brain barrier. Objective: The Phenytoin derivatives were designed, synthesized, and characterized to meet the structural necessities indispensable for antiepileptic activity. Method: Firstly, the chloroacetylation of the 5,5-diphenyl hydantoin was carried out, and then various substituted phenols were added to it. The synthesized compounds were characterized and evaluated for antianxiety activity by elevated plus maze method and antiepileptic activity by using subcutaneous pentylenetetrazole (scPTZ) and maximal electroshock (MES) models and neurotoxicity. Result: The number of derivatives of 5,5-diphenyl hydantoin was developed and optimized. The number of parameters was optimized which reveal that the compound containing chloro group such as C3 and C6 showed imperative potential when compared with the standard drug Diazepam. Other compounds containing nitro and methyl group were also found to possess activity. Conclusion: It was summarized that the new compounds of 5,5-diphenyl hydantoin derivatives were synthesized. The results of the data show that the compound containing chloro group is more potent for CNS activity. The new compounds have the probability of being optimized further to engender new scaffolds to treat various CNS disorders.

Keywords: phenytoin, parameters, CNS activity, blood-brain barrier, Log P, CNS active

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Authors: Kamyar Moradi

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Background: There is mixed evidence regarding the association between recreational cannabinoid use and memory performance. One of the major reasons for the present controversy is different cannabinoid use-related covariates that influence the cognitive status of an individual. Adjustment of these confounding variables provides accurate insight into the real effects of cannabinoid use on memory status. In this study, we sought to investigate the association between recent recreational cannabinoid use and memory performance while correcting the model for other possible covariates such as demographic characteristics and duration, and amount of cannabinoid use. Methods: Cannabinoid users were assigned to two groups based on the results of THC urine drug screen test (THC+ group: n = 110, THC- group: n = 410). THC urine drug screen test has a high sensitivity and specificity in detecting cannabinoid use in the last 3-4 weeks. The memory domain of NIH Toolbox battery and brain MRI volumetric measures were compared between the groups while adjusting for confounding variables. Results: After Benjamini-Hochberg p-value correction, the performance in all of the measured memory outcomes, including vocabulary comprehension, episodic memory, executive function/cognitive flexibility, processing speed, reading skill, working memory, and fluid cognition, were significantly weaker in THC+ group (p values less than 0.05). Also, volume of gray matter, left supramarginal, right precuneus, right inferior/middle temporal, right hippocampus, left entorhinal, and right pars orbitalis regions were significantly smaller in THC+ group. Conclusions: this study provides evidence regarding the acute effect of recreational cannabis use on memory performance. Further studies are warranted to confirm the results.

Keywords: brain MRI, cannabis, memory, recreational use, THC urine test

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Authors: Muhammad Muzamil Khan, Asadullah Madni, Nina Filipczek, Jiayi Pan, Nayab Tahir, Hassan Shah, Vladimir Torchilin

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Lipid-polymer hybrid nanoparticles (LPHNP) are delivery systems for controlled drug delivery at tumor sites. The superior biocompatible properties of lipid and structural advantages of polymer can be obtained via this system for controlled drug delivery. In the present study, cisplatin-loaded lipid-chitosan hybrid nanoparticles were formulated by the single step ionic gelation method based on ionic interaction of positively charged chitosan and negatively charged lipid. Formulations with various chitosan to lipid ratio were investigated to obtain the optimal particle size, encapsulation efficiency, and controlled release pattern. Transmission electron microscope and dynamic light scattering analysis demonstrated a size range of 181-245 nm and a zeta potential range of 20-30 mV. Compatibility among the components and the stability of formulation were demonstrated with FTIR analysis and thermal studies, respectively. The therapeutic efficacy and cellular interaction of cisplatin-loaded LPHNP were investigated using in vitro cell-based assays in A2780/ADR ovarian carcinoma cell line. Additionally, the cisplatin loaded LPHNP exhibited a low toxicity profile in rats. The in-vivo pharmacokinetics study also proved a controlled delivery of cisplatin with enhanced mean residual time and half-life. Our studies suggested that the cisplatin-loaded LPHNP being a promising platform for controlled delivery of cisplatin in cancer therapy.

Keywords: cisplatin, lipid-polymer hybrid nanoparticle, chitosan, in vitro cell line study

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Authors: Pimpak Phumat, Sakornrat Khongkhunthian, Thomas Rades, Anette Müllertz, Siriporn Okonogi

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Self-nanoemulsifying drug delivery systems (SNEDDS) containing 4-allylpyrocatechol (AP) extracted from Piper betle were developed to enhance water solubility of AP by using modeling and design (MODDE) program. The amount of AP in each SNEDDS formulation was determined by using high-performance liquid chromatography. The formulation consisted of 20% Miglyol®812N, 40 % Kolliphor®RH40, 30 % Maisine®35-1 and 10 % ethanol was found to be the best SNEDDS that provided the highest loading capacity of AP. (141.48±15.64 mg/g SNEDDS). The system also showed miscibility with water. The particle shape and size of the AP-SNEDDS after dispersing in water was investigated by using a transmission electron microscope and photon correlation spectrophotometer, respectively. The results showed that they were a spherical shape, having a particle size of 34.27 ± 1.14 nm with a narrow size distribution of 0.17 ± 0.04. The particles showed negative zeta potential with a value of -21.66 ± 2.09 mV. Antibacterial activity of AP-SNEDDS containing 1.5 mg/mL of AP was investigated against Streptococcus intermedius. The effect of this system on S. intermedius cells was observed by a scanning electron microscope (SEM). The results from SEM revealed that the bacterial cells were obviously destroyed. Killing kinetic study of AP-SNEDDS was carried out. It was found that the killing rate of AP-SNEDDS against S. intermedius was dose-dependent and the bacterial reduction was 79.86 ± 0.45 % within 30 min. In comparison with chlorhexidine (CHX), AP-SNEDDS showed similar antibacterial effects against S. intermedius. It is concluded that SNEDDS is a potential system for enhancing water solubility of AP. The antibacterial study reveals that AP-SNEDDS can be a promising system to treat bacterial infection caused by S. intermedius.

Keywords: SNEDDS, 4-allylpyrocathecol, solubility, antibacterial activity, Streptococcus intermedius

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Authors: Ved Vrat Verma, Rani Gupta, Manisha Goel

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γ-glutamyltranspeptidase (GGT: EC 2.3.2.2) is an N-terminal nucleophile hydrolase conserved in all three domains of life. GGT plays a key role in glutathione metabolism where it catalyzes the breakage of the γ-glutamyl bonds and transfer of γ-glutamyl group to water (hydrolytic activity) or amino acids or short peptides (transpeptidase activity). GGTs from bacteria, archaea, and eukaryotes (human, rat and mouse) are homologous proteins sharing >50% sequence similarity and conserved four layered αββα sandwich like three dimensional structural fold. These proteins though similar in their structure to each other, are quite diverse in their enzyme activity: some GGTs are better at hydrolysis reactions but poor in transpeptidase activity, whereas many others may show opposite behaviour. GGT is known to be involved in various diseases like asthma, parkinson, arthritis, and gastric cancer. Its inhibition prior to chemotherapy treatments has been shown to sensitize tumours to the treatment. Microbial GGT is known to be a virulence factor too, important for the colonization of bacteria in host. However, all known inhibitors (mimics of its native substrate, glutamate) are highly toxic because they interfere with other enzyme pathways. However, a few successful efforts have been reported previously in designing species specific inhibitors. We aim to leverage the diversity seen in GGT family (pathogen vs. eukaryotes) for designing specific inhibitors. Thus, in the present study, we have used DIVERGE software to identify sites in GGT proteins, which are crucial for the functional and structural divergence of these proteins. Since, type II divergence sites vary in clade specific manner, so type II divergent sites were our focus of interest throughout the study. Type II divergent sites were identified for pathogen vs. eukaryotes clusters and sites were marked on clade specific representative structures HpGGT (2QM6) and HmGGT (4ZCG) of pathogen and eukaryotes clade respectively. The crucial divergent sites within 15 A radii of the binding cavity were highlighted, and in-silico mutations were performed on these sites to delineate the role of these sites on the mechanism of catalysis and protein folding. Further, the amino acid network (AAN) analysis was also performed by Cytoscape to delineate assortative mixing for cavity divergent sites which could strengthen our hypothesis. Additionally, molecular dynamics simulations were performed for wild complexes and mutant complexes close to physiological conditions (pH 7.0, 0.1 M ionic strength and 1 atm pressure) and the role of putative divergence sites and structural integrities of the homologous proteins have been analysed. The dynamics data were scrutinized in terms of RMSD, RMSF, non-native H-bonds and salt bridges. The RMSD, RMSF fluctuations of proteins complexes are compared, and the changes at protein ligand binding sites were highlighted. The outcomes of our study highlighted some crucial divergent sites which could be used for novel inhibitors designing in a species-specific manner. Since, for drug development, it is challenging to design novel drug by targeting similar protein which exists in eukaryotes, so this study could set up an initial platform to overcome this challenge and help to deduce the more effective targets for novel drug discovery.

Keywords: γ-glutamyltranspeptidase, divergence, species-specific, drug design

Procedia PDF Downloads 254

Authors: Kitti Supchukun, Kris Angkanaporn, Teerapong Yata

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The product innovation using a nutraceutical delivery system on improving the growth performance of broilers is the product planning and development to solve the antibiotics banning policy incurred in the local and global livestock production system. Restricting the use of antibiotics can reduce the quality of chicken meat and increase pathogenic bacterial contamination. Although other alternatives were used to replace antibiotics, the efficacy was inconsistent, reflecting on low chicken growth performance and contaminated products. The product innovation aims to effectively deliver the selected active ingredients into the body. This product is tested on the pharmaceutical lab scale and on the farm-scale for market feasibility in order to create product innovation using the nutraceutical delivery system model. The model establishes the product standardization and traceable quality control process for farmers. The study is performed using mixed methods. Starting with a qualitative method to find the farmers' (consumers) demands and the product standard, then the researcher used the quantitative research method to develop and conclude the findings regarding the acceptance of the technology and product performance. The survey has been sent to different organizations by random sampling among the entrepreneur’s population including integrated broiler farm, broiler farm, and other related organizations. The mixed-method results, both qualitative and quantitative, verify the user and lead users' demands since they provide information about the industry standard, technology preference, developing the right product according to the market, and solutions for the industry problems. The product innovation selected nutraceutical ingredients that can solve the following problems in livestock; bactericidal, anti-inflammation, gut health, antioxidant. The combinations of the selected nutraceutical and nanostructured lipid carriers (NLC) technology aim to improve chemical and pharmaceutical components by changing the structure of active ingredients into nanoparticle, which will be released in the targeted location with accurate concentration. The active ingredients in nanoparticle form are more stable, elicit antibacterial activity against pathogenic Salmonella spp and E.coli, balance gut health, have antioxidant and anti-inflammation activity. The experiment results have proven that the nutraceuticals have an antioxidant and antibacterial activity which also increases the average daily gain (ADG), reduces feed conversion ratio (FCR). The results also show a significant impact on the higher European Performance Index that can increase the farmers' profit when exporting. The product innovation will be tested in technology acceptance management methods from farmers and industry. The production of broiler and commercialization analyses are useful to reduce the importation of animal supplements. Most importantly, product innovation is protected by intellectual property.

Keywords: nutraceutical, nano structure lipid carrier, anti-microbial drug resistance, broiler, Salmonella

Procedia PDF Downloads 152

Authors: Gajanan M. Sonwane

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The computational studies on 2-phenazinamines with their protein targets have been carried out to design compounds with potential anticancer activity. This strategy of designing compounds possessing selectivity over specific tyrosine kinase has been achieved through G-QSAR and molecular docking studies. The objective of this research has been to design newer 2-phenazinamine derivatives as Bcr-Abl tyrosine kinase inhibitors by G-QSAR, molecular docking studies followed by wet-lab studies along with evaluation of their anticancer potential. Computational chemistry was done by using VLife MDS 4.3 and Autodock 4.2 followed by wet-lab experiments for synthesizing 2-phenazinamine derivatives. The chemical structures of ligands in 2D were drawn by employing Chemdraw 2D Ultra 8.0 and were converted into 3D. These were optimized by using a semi-empirical method called MOPAC. The protein structure was retrieved from RCSC protein data bank as a PDB file. The binding interactions of protein and ligands were done by using PYMOL. The molecular properties of the designed compounds were predicted in silico by using Osiris property explorer. The parent compound 2-phenazinamine was synthesized by reduction of 2, 4-dinitro-N-phenyl-benzenamine in the presence of tin chloride followed by cyclization in the presence of nitrobenzene and magnesium sulfate. The derivatization at the amino function of 2-phenazinamine was performed by treating parent compound with various aldehydes in the presence of dicyclohexylcarbodiimide (DCC) and urea to afford 2-(2-chlorophenyl)-3-(phenazine-2-yl) thiazolidine-4-one. Synthesized 39 novel derivatives of 2-phenazinamine and performed antioxidant activity, anti antiproliferative on the bulb of onion and anticancer activity on cell line showing significant competition with marked blockbuster drug imatinib.

Keywords: computer-aided drug design, tyrosin kinases, anticancer, docking

Procedia PDF Downloads 122

Authors: Saman Ahani, Aboozar Dehghan, Roham Vali, Hamid Salehian, Amin Ebrahimi

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Pulsed-wave (PW) doppler ultrasonography is a non-invasive, relatively accurate imaging technique that can measure blood speed. The imaging could be obtained via the common carotid artery, as one of the main vessels supplying the blood of vital organs. In horses, factors such as susceptibility to depression of the cardiovascular system and their large muscular mass have rendered them vulnerable to changes in blood speed. One of the most important factors causing blood velocity changes is the administration of anesthetic drugs, including Ketamine and Acepromazine. Thus, in this study, the Pulsed-wave doppler technique was performed to assess the highest blood velocity in the common carotid artery following administration of Ketamine and Acepromazine. Six male and six female healthy Kurdish horses weighing 351 ± 46 kg (mean ± SD) and aged 9.2 ± 1.7 years (mean ± SD) were housed under animal welfare guidelines. After fasting for six hours, the normal blood flow velocity in the common carotid artery was measured using a Pulsed-wave doppler ultrasonography machine (BK Medical, Denmark), and a high-frequency linear transducer (12 MHz) without applying any sedative drugs as a control group. The same procedure was repeated after each individual received the following medications: 1.1, 2.2 mg/kg Ketamine (Pfizer, USA), and 0.5, 1 mg/kg Acepromizine (RACEHORSE MEDS, Ukraine), with an interval of 21 days between the administration of each dose and/or drug. The ultrasonographic study was done five (T5) and fifteen (T15) minutes after injecting each dose intravenously. Lastly, the statistical analysis was performed using SPSS software version 22 for Windows and a P value less than 0.05 was considered to be statistically significant. Five minutes after administration of Ketamine (1.1, 2.2 mg/kg) in both male and female horses, the blood velocity decreased to 38.44, 34.53 cm/s in males, and 39.06, 34.10 cm/s in females in comparison to the control group (39.59 and 40.39 cm/s in males and females respectively) while administration of 0.5 mg/kg Acepromazine led to a significant rise (73.15 and 55.80 cm/s in males and females respectively) (p<0.05). It means that the most drastic change in blood velocity, regardless of gender, refers to the latter dose/drug. In both medications and both genders, the increase in doses led to a decrease in blood velocity compared to the lower dose of the same drug. In all experiments in this study, the blood velocity approached its normal value at T15. In another study comparing the blood velocity changes affected by Ketamine and Acepromazine through femoral arteries, the most drastic changes were attributed to Ketamine; however, in this experiment, the maximum blood velocity was observed following administration of Acepromazine via the common carotid artery. Therefore, further experiments using the same medications are suggested using Pulsed-wave doppler measuring the blood velocity changes in both femoral and common carotid arteries simultaneously.

Keywords: Acepromazine, common carotid artery, horse, ketamine, pulsed-wave doppler ultrasonography

Procedia PDF Downloads 110

Authors: V. Bezverbny

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The actuality of the project deals with stable growing of deviant behavior’ statistics among Moscow citizens. During the recent years the socioeconomic health, wealth and life expectation of Moscow residents is regularly growing up, but the limits of crime and drug addiction have grown up seriously. Another serious Moscow problem has been economical stratification of population. The cost of identical residential areas differs at 2.5 times. The project is aimed at complex research and the development of methodology for main factors and reasons evaluation of deviant behavior growing in Moscow. The main project objective is finding out the links between the urban environment quality and dynamics of citizens’ deviant behavior in regional and municipal aspect using the statistical research methods and GIS modeling. The conducted research allowed: 1) to evaluate the dynamics of deviant behavior in Moscow different administrative districts; 2) to describe the reasons of crime increasing, drugs addiction, alcoholism, suicides tendencies among the city population; 3) to develop the city districts classification based on the level of the crime rate; 4) to create the statistical database containing the main indicators of Moscow population deviant behavior in 2010-2015 including information regarding crime level, alcoholism, drug addiction, suicides; 5) to present statistical indicators that characterize the dynamics of Moscow population deviant behavior in condition of expanding the city territory; 6) to analyze the main sociological theories and factors of deviant behavior for concretization the deviation types; 7) to consider the main theoretical statements of the city sociology devoted to the reasons for deviant behavior in megalopolis conditions. To explore the level of deviant behavior’ factors differentiation, the questionnaire was worked out, and sociological survey involved more than 1000 people from different districts of the city was conducted. Sociological survey allowed to study the socio-economical and psychological factors of deviant behavior. It also included the Moscow residents’ open-ended answers regarding the most actual problems in their districts and reasons of wish to leave their place. The results of sociological survey lead to the conclusion that the main factors of deviant behavior in Moscow are high level of social inequality, large number of illegal migrants and bums, nearness of large transport hubs and stations on the territory, ineffective work of police, alcohol availability and drug accessibility, low level of psychological comfort for Moscow citizens, large number of building projects.

Keywords: deviant behavior, megapolis, Moscow, urban environment, social stratification

Procedia PDF Downloads 178

Authors: N. Tadayon, H. Yousefnia, S. Zolghadri, A. Ramazani, A. R. Jalilian

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Bone metastases occur in many patients with solid malignant tumors. Recently, 1,2 propylene di-amino tetra methylenephosphonic acid (PDTMP) has been introduced as a suitable carrier in the development of therapeutic bone-avid radiopharmaceuticals. In this study, due to the desirable characteristics of 68Ga, 68Ga-PDTMP was prepared. 68Ga was obtained from SnO2 based generator. A stock solution of PDTMP was prepared by dissolving in 2 N NaOH. A certain volume of the stock solution was added to the vial containing 68GaCl3 and the pH of the mixture was adjusted to 4 using HEPES. Radiochemical purity of the radiolabelled complex was checked by thin layer chromatography. 68Ga-PDTMP was prepared in only 15 min with radiochemical purity of more than 98%. This new bone-seeking complex can be considered as a good candidate of PET-based radiopharmaceutical for imaging of bone metastases.

Keywords: bone metastases, Ga-68, imaging, PDTMP

Procedia PDF Downloads 279

Authors: Mohsen Shati, Seyede Salehe Mortazavi, Seyed Kazem Malakouti, Hamidreza Khanke Fazlollah Ahmadi

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Taking unnecessary or excessive medication or using drugs with no indication (polypharmacy) by people of all ages, especially the elderly, is associated with increased adverse drug reactions (ADR), medical errors, hospitalization and escalating the costs. It may be facilitated or impeded by the healthcare system. In this study, we are going to describe the role of the health system in the practice of polypharmacy in Iranian elderly. In this Inductive qualitative content analysis using Graneheim and Lundman methods, purposeful sample selection until saturation has been made. Participants have been selected from doctors, pharmacists, policy-makers and the elderly. A total of 25 persons (9 men and 16 women) have participated in this study. Data analysis after incorporating codes with similar characteristics revealed 14 subcategories and six main categories of the referral system, physicians’ accessibility, health data management, drug market, laws enforcement, and social protection. Some of the conditions of the healthcare system have given rise to polypharmacy in the elderly. In the absence of a comprehensive specialty and subspecialty referral system, patients may go to any physician office so may well be confused about numerous doctors' prescriptions. Electronic records not being prepared for the patients, failure to comply with laws, lack of robust enforcement for the existing laws and close surveillance are among the contributing factors. Inadequate insurance and supportive services are also evident. Age-specific care providing has not yet been institutionalized, while, inadequate specialist workforce playing a major role. So, one may not ignore the health system as contributing factor in designing effective interventions to fix the problem.

Keywords: elderly, polypharmacy, health system, qualitative study

Procedia PDF Downloads 137

Authors: Omoruyi Gold Idemudia, Alexander P. Sadimenko

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The synthesis of N-heterocycles with novel properties, having broad spectrum biological activities that may become alternative medicinal drugs, have been attracting a lot of research attention due to the emergence of medicinal drug’s limitations such as disease resistance and their toxicity effects among others. Acylpyrazolones have been employed as pharmaceuticals as well as analytical reagent and their application as coordination complexes with transition metal ions have been well established. By way of a condensation reaction with amines acylpyrazolone ketones form a more chelating and superior group of compounds known as azomethines. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one was reacted with phenylhydrazine to get a new phenylhydrazone which was further reacted with aqueous solutions of palladium and platinum salts, in an effort towards the discovery of transition metal based synthetic drugs. The compounds were characterized by means of analytical, spectroscopic, thermogravimetric analysis TGA, as well as x-ray crystallography. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one phenylhydrazone crystallizes in a triclinic crystal system with a P-1 (No. 2) space group based on x-ray crystallography. The bidentate ON ligand formed a square planar geometry on coordinating with metal ions based on FTIR, electronic and NMR spectra as well as magnetic moments. Reported compounds showed antibacterial activities against the nominated bacterial isolates using the disc diffusion technique at 20 mg/ml in triplicates. The metal complexes exhibited a better antibacterial activity with platinum complex having an MIC value of 0.63 mg/ml. Similarly, ligand and complexes also showed antioxidant scavenging properties against 2, 2-diphenyl-1-picrylhydrazyl DPPH radical at 0.5mg/ml relative to ascorbic acid (standard drug).

Keywords: acylpyrazolone, antibacterial studies, metal complexes, phenylhydrazone, spectroscopy

Procedia PDF Downloads 237

Authors: Nisa Mohan

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Adverse drug event (ADE) related hospital admissions are common among older people. The first step in prevention is accurately estimating the prevalence of ADE admissions. Clinical coding is an efficient method to estimate the prevalence of ADE admissions. The objective of the study is to estimate the rate of under-coding of ADE admissions in older people in New Zealand and to explore how clinical coders decide whether or not to code an admission as an ADE. There has not been any research in New Zealand to explore these areas. This study is done using a mixed-methods approach. Two common and serious ADEs in older people, namely bleeding and hypoglycaemia were selected for the study. In study 1, eight hundred medical records of people aged 65 years and above who are admitted to hospital due to bleeding and hypoglycemia during the years 2015 – 2016 were selected for quantitative retrospective medical records review. This selection was made to estimate the proportion of ADE-related bleeding and hypoglycemia admissions that are not coded as ADEs. These files were reviewed and recorded as to whether the admission was caused by an ADE. The hospital discharge data were reviewed to check whether all the ADE admissions identified in the records review were coded as ADEs, and the proportion of under-coding of ADE admissions was estimated. In study 2, thirteen clinical coders were selected to conduct qualitative semi-structured interviews using a general inductive approach. Participants were selected purposively based on their experience in clinical coding. Interview questions were designed in a way to investigate the reasons for the under-coding of ADE admissions. The records review study showed that 35% (Cl 28% - 44%) of the ADE-related bleeding admissions and 22% of the ADE-related hypoglycemia admissions were not coded as ADEs. Although the quality of clinical coding is high across New Zealand, a substantial proportion of ADE admissions were under-coded. This shows that clinical coding might under-estimate the actual prevalence of ADE related hospital admissions in New Zealand. The interviews with the clinical coders added that lack of time for searching for information to confirm an ADE admission, inadequate communication with clinicians, along with coders’ belief that an ADE is a small thing might be the potential reasons for the under-coding of the ADE admissions. This study urges the coding policymakers, auditors, and trainers to engage with the unconscious cognitive biases and short-cuts of the clinical coders. These results highlight that further work is needed on interventions to improve the clinical coding of ADE admissions, such as providing education to coders about the importance of ADEs, education to clinicians about the importance of clear and confirmed medical records entries, availing pharmacist service to improve the detection and clear documentation of ADE admissions and including a mandatory field in the discharge summary about external causes of diseases.

Keywords: adverse drug events, bleeding, clinical coders, clinical coding, hypoglycemia

Procedia PDF Downloads 112

Authors: Antonina Semakova, Karim Mynbaev, Nikolai Bazhenov, Anton Chernyaev, Sergei Kizhaev, Nikolai Stoyanov

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At present, heterostructures are used for fabrication of almost all types of optoelectronic devices. Our research focuses on the optoelectronic properties of InAs(Sb) solid solutions that are widely used in fabrication of light emitting diodes (LEDs) operating in middle wavelength infrared range (MWIR). This spectral range (2-6 μm) is relevant for laser diode spectroscopy of gases and molecules, for systems for the detection of explosive substances, medical applications, and for environmental monitoring. The fabrication of MWIR LEDs that operate efficiently at room temperature is mainly hindered by the predominance of non-radiative Auger recombination of charge carriers over the process of radiative recombination, which makes practical application of LEDs difficult. However, non-radiative recombination can be partly suppressed in quantum-well structures. In this regard, studies of such structures are quite topical. In this work, electroluminescence (EL) of LED heterostructures based on InAs(Sb) epitaxial films with the molar fraction of InSb ranging from 0 to 0.09 and multi quantum-well (MQW) structures was studied in the temperature range 4.2-300 K. The growth of the heterostructures was performed by metal-organic chemical vapour deposition on InAs substrates. On top of the active layer, a wide-bandgap InAsSb(Ga,P) barrier was formed. At low temperatures (4.2-100 K) stimulated emission was observed. As the temperature increased, the emission became spontaneous. The transition from stimulated emission to spontaneous one occurred at different temperatures for structures with different InSb contents in the active region. The temperature-dependent carrier lifetime, limited by radiative recombination and the most probable Auger processes (for the materials under consideration, CHHS and CHCC), were calculated within the framework of the Kane model. The effect of various recombination processes on the carrier lifetime was studied, and the dominant role of Auger processes was established. For MQW structures quantization energies for electrons, light and heavy holes were calculated. A characteristic feature of the experimental EL spectra of these structures was the presence of peaks with energy different from that of calculated optical transitions between the first quantization levels for electrons and heavy holes. The obtained results showed strong effect of the specific electronic structure of InAsSb on the energy and intensity of optical transitions in nanostructures based on this material. For the structure with MQWs in the active layer, a very weak temperature dependence of EL peak was observed at high temperatures (>150 K), which makes it attractive for fabricating temperature-resistant gas sensors operating in the middle-infrared range.

Keywords: Electroluminescence, InAsSb, light emitting diode, quantum wells

Procedia PDF Downloads 192

Authors: Haykal. Kay-Anne

Abstract:

The health and well-being of students is a priority for the Faculty of Medicine at the University of Ottawa. The demands of medical studies are extreme, and many studies confirm that the prevalence of psychological distress is very high among medical students and that it is higher than that of the general population of the same age. The main goal is to identify risk factors for mental health among medical students at the University of Ottawa. The secondary objectives are to determine the variation of these risk factors according to demographic variables, as well as to determine if there is a change in the mental health of students during the 1st and 3rd years of their study. Medical students have a mandatory first and third-year wellness check meeting. This assessment includes a questionnaire on demographic information, mental health, and risk factors such as physical health, sleep, social support, financial stress, education and career, stress and drug use and/or alcohol. Student responses were converted to numerical values and analyzed statistically. The results show that 61% of the variation in the mean of the mental health score is explained by the following risk factors (R2 = 0.61, F (9.396) = 67.197, p < 0.01): lack of sleep and fatigue (β = 0.281, p < 0.001), lack of social support (β = 0.217, p <0.001), poor study or career development (β = 0.195, p < 0.001) and an increase stress and drug and alcohol use (β = -0.239, p < 0.001). No demographic variable has a significant effect on the presence of risk factors. In addition, fixed-effects regression demonstrated significantly lower mental health (p < 0.1) among first-year students (M = 0.587, SD = 0.072) than among third-year students (M = 0.719, SD = 0.071). This preliminary study indicates the need to continue data collection and analysis to increase the significance of the study results. As risk factors are present at the beginning of medical studies, it is important to offer resources to students very early in their medical studies and to have close monitoring and supervision.

Keywords: assessment of mental health, medical students, risk factors for mental health, wellness assessment

Procedia PDF Downloads 106

Authors: Soma Banerjee, Aamen Talukdar, Argha Mandal, Dipankar Chaudhuri

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Japanese Encephalitis is a major infectious disease with nearly half the world’s population living in areas where it is prevalent. Currently, treatment for it involves only supportive care and symptom management through vaccination. Due to the lack of antiviral drugs against Japanese Encephalitis Virus (JEV), the quest for such agents remains a priority. For these reasons, simulation studies of drug targets against JEV are important. Towards this purpose, docking experiments of the kinase inhibitors were done against the chosen target NS3 helicase as it is a nucleoside binding protein. Previous efforts regarding computational drug design against JEV revealed some lead molecules by virtual screening using public domain software. To be more specific and accurate regarding finding leads, in this study a proprietary software Schrödinger-GLIDE has been used. Druggability of the pockets in the NS3 helicase crystal structure was first calculated by SITEMAP. Then the sites were screened according to compatibility with ATP. The site which is most compatible with ATP was selected as target. Virtual screening was performed by acquiring ligands from databases: KinaseSARfari, KinaseKnowledgebase and Published inhibitor Set using GLIDE. The 25 ligands with best docking scores from each database were re-docked in XP mode. Protein structure alignment of NS3 was performed using VAST against MMDB, and similar human proteins were docked to all the best scoring ligands. The low scoring ligands were chosen for further studies and the high scoring ligands were screened. Seventy-three ligands were listed as the best scoring ones after performing HTVS. Protein structure alignment of NS3 revealed 3 human proteins with RMSD values lesser than 2Å. Docking results with these three proteins revealed the inhibitors that can interfere and inhibit human proteins. Those inhibitors were screened. Among the ones left, those with docking scores worse than a threshold value were also removed to get the final hits. Analysis of the docked complexes through 2D interaction diagrams revealed the amino acid residues that are essential for ligand binding within the active site. Interaction analysis will help to find a strongly interacting scaffold among the hits. This experiment yielded 21 hits with the best docking scores which could be investigated further for their drug like properties. Aside from getting suitable leads, specific NS3 helicase-inhibitor interactions were identified. Selection of Target modification strategies complementing docking methodologies which can result in choosing better lead compounds are in progress. Those enhanced leads can lead to better in vitro testing.

Keywords: antivirals, docking, glide, high-throughput virtual screening, Japanese encephalitis, ns3 helicase

Procedia PDF Downloads 211

Authors: Saravanan Govindaraju, Kyusik Yun

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The purpose of this study is to develop the chitosan doped curcumin gold cluster nanofiber for wound healing and skin cancer drug delivery applications. Chitosan is a typical marine polysaccharide composed of glucosamine and n-acetyl glucosamine biodegradable and biocompatible polymer. Curcumin is a natural bioactive molecule obtained from Curcuma longo, it mostly occurs in some Asian countries like India and China. It has naturally antioxidant, antimicrobial, wound healing and anticancer property. Due to this advantage, we prepared a combination of natural polymer chitosan with Curcumin and gold nanocluster nanofiber (CH-CUR-AuNCs nanofibers). The prepared nanofiber was characterized by using Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). Antibacterial studies were performed with E.coli and S.aureus. Antioxidant assay, drug release test, and cytotoxicity will be evaluated. Prepared nanofiber emits low intensity of red fluorescent. The FTIR confirm the presence of chitosan and Curcumin in the nanofiber. In vitro study clearly shows the antibacterial activity against the gram negative and gram positive bacteria. Particularly, synthesised nanofibers provide better antibacterial activity against gram negative than gram positive. Cytotoxicity study also provides better killing rate in cancer cell, biocompatible with normal cell. Prepared CH-CUR-AuNCs nanofibers provide the better killing rate to bacterial strains and cancer cells. Finally, prepared nanofiber can be possible to use for wound healing dressing, patch for skin cancer and other biomedical applications.

Keywords: curcumin, chitosan, gold clusters, nanofibers

Procedia PDF Downloads 251