Search results for: drug transport

Authors: Joe Collins, Matthias Rother

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Background: Oral non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the relief of joint pain during and post-exercise. However, oral NSAIDs increase the risk of systemic side effects, even in healthy individuals, and retard recovery from muscle soreness. TDT 064 (Flexiseq®), a topical formulation containing ultra-deformable drug-free Sequessome™ vesicles, has demonstrated equivalent efficacy to oral celecoxib in reducing osteoarthritis-associated joint pain and stiffness. TDT 064 does not cause NSAID-related adverse effects. We describe clinical study data and a case report on the effectiveness of TDT 064 in reducing joint pain after exercise. Methods: Participants with a pain score ≥3 (10-point scale) 12–16 hours post-exercise were randomized to receive TDT 064 plus oral placebo, TDT 064 plus oral ketoprofen, or ketoprofen in ultra-deformable phospholipid vesicles plus oral placebo. Results: In the 168 study participants, pain scores were significantly higher with oral ketoprofen plus TDT 064 than with TDT 064 plus placebo in the 7 days post-exercise (P = 0.0240) and recovery from muscle soreness was significantly longer (P = 0.0262). There was a low incidence of adverse events. These data are supported by clinical experience. A 24-year-old male professional rugby player suffered a traumatic lisfranc fracture in March 2014 and underwent operative reconstruction. He had no relevant medical history and was not receiving concomitant medications. He had undergone anterior cruciate ligament reconstruction in 2008. The patient reported restricted training due to pain (score 7/10), stiffness (score 9/10) and poor function, as well as pain when changing direction and running on consecutive days. In July 2014 he started using TDT 064 twice daily at the recommended dose. In November 2014 he noted reduced pain on running (score 2-3/10), decreased morning stiffness (score 4/10) and improved joint mobility and was able to return to competitive rugby without restrictions. No side effects of TDT 064 were reported. Conclusions: TDT 064 shows efficacy against exercise- and injury-induced joint pain, as well as that associated with osteoarthritis. It does not retard muscle soreness recovery after exercise compared with an oral NSAID, making it an alternative approach for the treatment of joint pain during and post-exercise.

Keywords: exercise, joint pain, TDT 064, phospholipid vesicles

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Authors: Achraf Al Faraj, Asma Sultana Shaik, Baraa Al Sayed

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Specific and effective targeting of drug delivery systems (DDS) to cancerous sites remains a major challenge for a better diagnostic and therapy. Recently, SWCNTs with their unique physicochemical properties and the ability to cross the cell membrane show promising in the biomedical field. The purpose of this study was first to develop a biocompatible iron oxide tagged SWCNTs as diagnostic nanoprobes to allow their noninvasive detection using MRI and their preferential targeting in a breast cancer murine model by placing an optimized flexible magnet over the tumor site. Magnetic targeting was associated to specific antibody-conjugated SWCNTs active targeting. The therapeutic efficacy of doxorubicin-conjugated SWCNTs was assessed, and the superiority of diffusion-weighted (DW-) MRI as sensitive imaging biomarker was investigated. Short Polyvinylpyrrolidone (PVP) stabilized water soluble SWCNTs were first developed, tagged with iron oxide nanoparticles and conjugated with Endoglin/CD105 monoclonal antibodies. They were then conjugated with doxorubicin drugs. SWCNTs conjugates were extensively characterized using TEM, UV-Vis spectrophotometer, dynamic light scattering (DLS) zeta potential analysis and electron spin resonance (ESR) spectroscopy. Their MR relaxivities (i.e. r1 and r2*) were measured at 4.7T and their iron content and metal impurities quantified using ICP-MS. SWCNTs biocompatibility and drug efficacy were then evaluated both in vitro and in vivo using a set of immunological assays. Luciferase enhanced bioluminescence 4T1 mouse mammary tumor cells (4T1-Luc2) were injected into the right inguinal mammary fat pad of Balb/c mice. Tumor bearing mice received either free doxorubicin (DOX) drug or SWCNTs with or without either DOX or iron oxide nanoparticles. A multi-pole 10x10mm high-energy flexible magnet was maintained over the tumor site during 2 hours post-injections and their properties and polarity were optimized to allow enhanced magnetic targeting of SWCNTs toward the primary tumor site. Tumor volume was quantified during the follow-up investigation study using a fast spin echo MRI sequence. In order to detect the homing of SWCNTs to the main tumor site, susceptibility-weighted multi-gradient echo (MGE) sequence was used to generate T2* maps. Apparent diffusion coefficient (ADC) measurements were also performed as a sensitive imaging biomarker providing early and better assessment of disease treatment. At several times post-SWCNT injection, histological analysis were performed on tumor extracts and iron-loaded SWCNT were quantified using ICP-MS in tumor sites, liver, spleen, kidneys, and lung. The optimized multi-poles magnet revealed an enhanced targeting of magnetic SWCNTs to the primary tumor site, which was found to be much higher than the active targeting achieved using antibody-conjugated SWCNTs. Iron-loading allowed their sensitive noninvasive tracking after intravenous administration using MRI. The active targeting of doxorubicin through magnetic antibody-conjugated SWCNTs nanoprobes was found to considerably decrease the primary tumor site and may have inhibited the development of metastasis in the tumor-bearing mice lung. ADC measurements in DW-MRI were found to significantly increase in a time-dependent manner after the injection of DOX-conjugated SWCNTs complexes.

Keywords: single-walled carbon nanotubes, nanomedicine, magnetic resonance imaging, cancer diagnosis and therapy

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Authors: N. Amraoui, D. Hammoutene

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We have performed a theoretical study using dispersion-corrected Density Functional Methods to evaluate a variety of artificial nucleobases as candidates for metal-mediated Hoogsteen-type base pairs. We focus on A-M-T Hoogsteen-type base pair with M=Co(II), Ru(I), Ni(I). All calculations are performed using (ADF 09) program. Metal-mediated Hoogsteen-type base pairs are studied as drug candidates, their geometry optimizations are performed at ZORA/TZ2P/BLYP-D level. The molecular geometries and different energies as total energies, coordination energies, Pauli interactions, orbital interactions and electrostatic energies are determined.

Keywords: chemistry, biology, density functional method, orbital interactions

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Authors: Chettou Souhaila, Soufi Omar, Roumia Mohammed Ammar

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Protecting the environment is to preserve the survival and future of humanity. Indeed, the environment is our source of food and drinking water, the air is our source of oxygen, the climate allows our survival and biodiversity are a potential drug reservoir. Preserving the environment is, therefore, a matter of survival. The objective of this project is to familiarize the general public with environmental problems not only with the theme of environmental protection, but also with the concept of biodiversity in different ecosystems. For it, the aim of our project was to create the Ecorium which is a place that preserves many species of plants of different ecosystems, schools, malls, buildings, offices, ecological transports, gardens, and many familial activities that participated in the ecosystems development, strategic biodiversity and sustainable development.

Keywords: ecological system, ecorium, environment, sustainable development

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Authors: S. Buloyan, V. Mamikonyan, H. Hakobyan, H. Harutyunyan, H. Gasparyan

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The liver is the strongest regenerating organ of the organism, and even with 2/3 surgically removed, it can regenerate completely. Hence, liver cirrhosis may only develop when the regenerating system is off. We present the results of a comparative study of structural and functional characteristics of rat liver tissue under the conditions of toxic liver cirrhosis development, induced by carbon tetrachloride, and its prevention/treatment by natural compounds with antioxidant and immune stimulating action. Studies were made on Wister rats, weighing 120~140 g. Grape seeds extracts, separately and in combination with well known anticirrhotic drug ursodeoxycholic acid (ursodiol) have demonstrated effectiveness in prevention of liver cirrhosis development and its treatment.

Keywords: carbon tetrachloride, GSE, liver cirrhosis, prevention, treatment

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Authors: Syrus Zimaze, George Nsimbe, Valley Mugwanya, Matiya Lule, Edgar Watson, Patrick Gwayambadde

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Physical inactivity is a growing global epidemic, also recognised as a major public health challenge. Globally, there are alarming rates of children reported with cardiovascular disease and obesity with limited interventions. In Sub Saharan Africa, there is limited information about involvement in physical activity especially among children aged 6 to 18 years. The aim of this study was to explore factors associated with involvement in physical activity among children in Uganda. Methods: We included all parents with children aged 6 to 18 years training with Excel Soccer Academy between January 2017 and June 2018. Physical activity definition was time spent participating in routine soccer training at the academy for more than 30 days. Each child's attendance was recorded, and parents provided demographic and social economic data. Data on predictors of physical activity involvement were collected using a standardized questionnaire. Descriptive statistics and frequency were used. Binary logistic regression was used at the multi variable level adjusting for education, residence, transport means and access to information technology. Results: Overall 356 parents were interviewed; Boys 318 (89.3%) engaged more in physical activity than girls. The median age for children was 13 years (IQR:6-18) and 42 years (IQR:37-49) among parents. The median time spent at the Excel soccer academy was 13.4 months (IQR: 4.6-35.7) Majority of the children attended formal education, p < 0.001). Factors associated with involvement in physical activity included: owning a permanent house compared to a rented house (odds ratio [OR] :2.84: 95% CI: 2.09-3.86, p < 0.0001), owning a car compared to using public transport (OR: 5.64 CI: 4.80-6.63, p < 0.0001), a parent having received formal education compared to non-formal education (OR: 2.93 CI: 2.47-3.46, p < 0.0001) and daily access to information technology (OR:0.40 CI:0.25-0.66, p < 0.001). Parent’s age and gender were not associated to involvement in physical activity. Conclusions: Socioeconomic factors were positively associated with involvement in physical activity with boys participating more than girls in soccer activities. More interventions are required geared towards increasing girl’s participation in physical activity and those targeting children from less privilege homes.

Keywords: physical activity, Sub-Saharan Africa, social economic factors, children

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Authors: Emre Kara, Ali Kurşun, Halil Aykul

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The lightweight sandwiches obtained with the use of various core materials such as foams, honeycomb, lattice structures etc., which have high energy absorbing capacity and high strength to weight ratio, are suitable for several applications in transport industry (automotive, aerospace, shipbuilding industry) where saving of fuel consumption, load carrying capacity increase, safety of vehicles and decrease of emission of harmful gases are very important aspects. While the sandwich structures with foams and honeycombs have been applied for many years, there is a growing interest on a new generation sandwiches with micro lattice cores. In order to produce these core structures, various production methods were created with the development of the technology. One of these production technologies is an additive manufacturing technique called selective laser sintering/melting (SLS/SLM) which is very popular nowadays because of saving of production time and achieving the production of complex topologies. The static bending and the dynamic low velocity impact tests of the sandwiches with carbon fiber/epoxy skins and the micro lattice cores produced via SLS/SLM were already reported in just a few studies. The goal of this investigation was the analysis of the flexural response of the sandwiches consisting of glass fiber reinforced plastic (GFRP) skins and the micro lattice cores manufactured via SLS under thermo-mechanical loads in order to compare the results in terms of peak load and absorbed energy values respect to the effect of core cell size, temperature and support span length. The micro lattice cores were manufactured using SLS technology that creates the product drawn by a 3D computer aided design (CAD) software. The lattice cores which were designed as body centered cubic (BCC) model having two different cell sizes (d= 2 and 2.5 mm) with the strut diameter of 0.3 mm were produced using titanium alloy (Ti6Al4V) powder. During the production of all the core materials, the same production parameters such as laser power, laser beam diameter, building direction etc. were kept constant. Vacuum Infusion (VI) method was used to produce skin materials, made of [0°/90°] woven S-Glass prepreg laminates. The combination of the core and skins were implemented under VI. Three point bending tests were carried out by a servo-hydraulic test machine with different values of support span distances (L = 30, 45, and 60 mm) under various temperature values (T = 23, 40 and 60 °C) in order to analyze the influences of support span and temperature values. The failure mode of the collapsed sandwiches has been investigated using 3D computed tomography (CT) that allows a three-dimensional reconstruction of the analyzed object. The main results of the bending tests are: load-deflection curves, peak force and absorbed energy values. The results were compared according to the effect of cell size, support span and temperature values. The obtained results have particular importance for applications that require lightweight structures with a high capacity of energy dissipation, such as the transport industry, where problems of collision and crash have increased in the last years.

Keywords: light-weight sandwich structures, micro lattice cores, selective laser sintering, transport application

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Authors: Agnieszka E. Laudy, Karolina Stępien, Sergiusz Lulinski, Krzysztof Durka, Stefan Tyski

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1,3-dihydro-1-hydroxy-2,1-benzoxaborole and its derivatives are a particularly interesting group of synthetic agents and were successfully employed in supramolecular chemistry medicine. The first important compounds, 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole and 5-chloro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole were identified as potent antifungal agents. In contrast, (S)-3-(aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole hydrochloride is in the second phase of clinical trials as a drug for the treatment of Gram-negative bacterial infections of the Enterobacteriaceae family and Pseudomonas aeruginosa. Equally important and difficult task is to search for compounds active against Gram-negative bacilli, which have multi-drug-resistance efflux pumps actively removing many of the antibiotics from bacterial cells. We have examined whether halogen-substituted benzoxaborole-based derivatives and their analogues possess antibacterial activity and are substrates for multi-drug-resistance efflux pumps. The antibacterial activity of 1,3-dihydro-3-hydroxy-1,1-dimethyl-1,2,3-benzosiloxaborole and 10 halogen-substituted its derivatives, as well as 1,2-phenylenediboronic acid and 3 synthesised fluoro-substituted its analogs, were evaluated. The activity against the reference strains of Gram-positive (n=5) and Gram-negative bacteria (n=10) was screened by the disc-diffusion test (0.4 mg of tested compounds was applied onto paper disc). The minimal inhibitory concentration values and the minimal bactericidal concentration values were estimated according to The Clinical and Laboratory Standards Institute and The European Committee on Antimicrobial Susceptibility Testing recommendations. During the minimal inhibitory concentration values determination with or without phenylalanine-arginine beta-naphthylamide (50 mg/L) efflux pump inhibitor, the concentrations of tested compounds ranged 0.39-400 mg/L in the broth medium supplemented with 1 mM magnesium sulfate. Generally, the studied benzosiloxaboroles and benzoxadiboroles showed a higher activity against Gram-positive cocci than against Gram-negative rods. Moreover, benzosiloxaboroles have the higher activity than benzoxadiboroles compounds. In this study, we demonstrated that substitution (mono-, di- or tetra-) of 1,3-dihydro-3-hydroxy-1,1-dimethyl-1,2,3-benzosiloxaborole with halogen groups resulted in an increase in antimicrobial activity as compared to the parent substance. Interestingly, the 6,7-dichloro-substituted parent substance was found to be the most potent against Gram-positive cocci: Staphylococcus sp. (minimal inhibitory concentration 6.25 mg/L) and Enterococcus sp. (minimal inhibitory concentration 25 mg/L). On the other hand, mono- and dichloro-substituted compounds were the most actively removed by efflux pumps present in Gram-negative bacteria mainly from Enterobacteriaceae family. In the presence of efflux pump inhibitor the minimal inhibitory concentration values of chloro-substituted benzosiloxaboroles decreased from 400 mg/L to 3.12 mg/L. Of note, the highest increase in bacterial susceptibility to tested compounds in the presence of phenylalanine-arginine beta-naphthylamide was observed for 6-chloro-, 6,7-dichloro- and 6,7-difluoro-substituted benzosiloxaboroles. In the case of Escherichia coli, Enterobacter cloacae and P. aeruginosa strains at least a 32-fold decrease in the minimal inhibitory concentration values of these agents were observed. These data demonstrate structure-activity relationships of the tested derivatives and highlight the need for further search for benzoxaboroles and related compounds with significant antimicrobial properties. Moreover, the influence of phenylalanine-arginine beta-naphthylamide on the susceptibility of Gram-negative rods to studied benzosiloxaboroles indicate that some tested agents are substrates for efflux pumps in Gram-negative rods.

Keywords: antibacterial activity, benzosiloxaboroles, efflux pumps, phenylalanine-arginine beta-naphthylamide

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Authors: R. C. Ferreira, H. H. C. De Lima, A. A. Cândido, O. M. Couto Junior, P. A. Arroyo, K. Q De Carvalho, G. F. Gauze, M. A. S. D. Barros

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Removal of the widespread used drug paracetamol from water was investigated using activated carbon originated from dende coconut mesocarp and babassu coconut mesocarp. Kinetic and equilibrium data were obtained at different values of pH. Babassu activated carbon showed higher efficiency due to its acidity and higher microporosity. Pseudo-second order model was better adjusted to the kinetic results. Equilibrium data may be represented by Langmuir equation. Lower solution pH provided better removal efficiency as the carbonil groups may be attracted by the positively charged carbon surface.

Keywords: adsorption, activated carbon, babassu, dende

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Authors: Lisdey Espinoza Pedraza

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Organised crime in Mexico evolves faster that our capacity to understand and explain it. Organised gangs have become successful entrepreneurs in many ways ad they have somehow mimicked the working ways of the authorities and in many cases, they have successfully infiltrated the governmental spheres. This business model is only possible under a clear scheme of rampant impunity. Impunity, however, is not exclusive to the PRI. Nor the PRI, PAN, or PRD can claim the monopoly of corruption, but what is worse is that none can claim full honesty in their acts either. The current security crisis in Mexico shows a crisis in the Mexican political party system. Corruption today is not only a problem of dishonesty and the correct use of public resources. It is the principal threat to Mexican democracy, governance, and national security.

Keywords: security, war on drugs, drug trafficking, Mexico, Latin America, United States

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Authors: Mathew Tran, Deepa Patel, Breann Prophete, Irandokht Khaki Najafabadi

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Status epilepticus is a neurological disorder requiring emergent control with medical therapy. Based on guideline recommendations for adults with status epilepticus, the first-line treatment is to start a benzodiazepine, as they are quick at seizure control. The second step is to initiate a non-benzodiazepine anti-epileptic drug to prevent refractory seizures. Studies show that the anti-epileptic drugs are approximately equivalent in status epilepticus control once a benzodiazepine has been given. This review provides a brief overview of the management of status epilepticus based on evidence from the literature and evidence-based guidelines.

Keywords: neurological disorder, seizure, status epilepticus, benzo diazepines, antiepileptic agents

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Authors: Tawqeer Ali Syed, Prakash Chandra

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This study aims to evaluate the antileishmanial activity of Nigella sativa black seed extract. This well-known plant extract was taken from the botanical garden of Kashmir. Materials and Methods: The methanolic extracts of these plants were screened for their antileishmanial activity against Leishmania major using 3‑(4.5‑dimethylthiazol‑2yl)‑2.5‑diphenyltetrazolium bromide assay or MTT assay. Results: The methanolic extract of Nigella sativa showed potential antileishmanial activity at an inhibition% value of 80.29% ± 0.65%. IC 50 was calculated after 48 hours to be 964.3 µg/ml. Conclusion: Considering these results, these medicinal plants from Kashmir could serve as potential drug sources for antileishmanial compounds.

Keywords: MTT assay, antileishmanial, cell viability, Nigella sativa

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Authors: Anik Barua, Rabiul Hossain, Labonno Barua, Rashadul Hossain, Nurul Absar

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Background: Globally, the burden of cancer is increasing consistently. Modern cancer therapies include lots of toxicity in the non-targeted organs reducing the life expectancy of the patients. Hence, scientists are trying to seek noble compounds from natural sources to treat cancer. Objectives: The objectives of the present study are to evaluate the phytochemicals, in vitro antioxidants, and in vivo and in silico anticancer study of various solvent fractions of Tinospora cordifolia (Willd.). Methodology: In this experiment, standard quantitative and qualitative assay methods were used to analyze the phytochemicals. The antioxidant activity was measured using the DPPH and ABTS scavenging methods. The in vivo antitumor activity is evaluated against Ehrlich ascites carcinoma (EAC) cell bearing in Swiss albino mice. In-silico ADME/T and molecular docking study were performed to assess the potential of stated phytochemicals against Transcription Factor STAT3b/DNA Complex of adenocarcinoma. Findings: Phytochemical screening confirmed the presence of flavonoids, alkaloids, glycosides, tannins, and carbohydrates. A significant amount of phenolic (20.19±0.3 mg/g GAE) and flavonoids (9.46±0.18 mg/g GAE) were found in methanolic extract in quantitative screening. Tinospora cordifolia methanolic extract showed promising DPPH and ABTS scavenging activity with the IC50 value of 1222.99 µg/mL and 1534.34 µg/mL, respectively, which was concentration dependent. In vivo anticancer activity in EAC cell-bearing mice showed significant (P < 0.05) percent inhibition of cell growth (60.12±1.22) was found at the highest dose compared with standard drug 5-Fluorouracil (81.18±1.28). Forty-two phytochemicals exhibit notable pharmacokinetics properties and passed drug-likeness screening tests in silico. In molecular docking study, (25S)-3Beta-acetoxy-5-alpha-22-beta-spirost-9(11)-en-12-beta-ol showed docking score (-8.5 kJ/mol) with significant non-bonding interactions with target enzyme. Conclusions: The results were found to be significant and confirmed that the methanolic extract of Tinospora cordifolia has remarkable antitumor activity with antioxidant potential. The Tinospora cordifolia methanolic extract may be considered a potent anticancer agent for advanced research.

Keywords: anticancer, antioxidant, Tinospora cordifolia, EAC cell

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Authors: Sandra Smart-Akande, Chaminda Hewage, Imtiaz Khan, Thanuja Mallikarachchi

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According to UK police-recorded data, there has been a substantial increase in knife-related crime and youth violence in the UK since 2014 particularly in the London boroughs. These crime rates are disproportionally distributed across London with the majority of these crimes occurring in the highly deprived areas of London and among young people aged 11 to 24 with large discrepancies across ethnicity, age, gender and borough of residence. Comprehensive studies and literature have identified risk factors associated with a knife carrying among youth to be Adverse Childhood Experience (ACEs), poor mental health, school or social exclusion, drug dealing, drug using, victim of violent crime, bullying, peer pressure or gang involvement, just to mention a few. ACEs are potentially traumatic events that occur in childhood, this can be experiences or stressful events in the early life of a child and can lead to an increased risk of damaging health or social outcomes in the latter life of the individual. Research has shown that children or youths involved in youth violence have had childhood experience characterised by disproportionate adverse childhood experiences and substantial literature link ACEs to be associated with criminal or delinquent behavior. ACEs are commonly grouped by researchers into: Abuse (Physical, Verbal, Sexual), Neglect (Physical, Emotional) and Household adversities (Mental Illness, Incarcerated relative, Domestic violence, Parental Separation or Bereavement). To the author's best knowledge, no study to date has investigated how household mental health (mental health of a parent or mental health of a child) and domestic violence (domestic violence on a parent or domestic violence on a child) is related to knife homicides across the local authorities areas of London. This study seeks to address the gap by examining a large sample of data from the London Metropolitan Police Force and Characteristics of Children in Need data from the UK Department for Education. The aim of this review is to identify and synthesise evidence from data and a range of literature to identify the relationship between adverse childhood experiences and youth violence in the UK. Understanding the link between ACEs and future outcomes can support preventative action.

Keywords: adverse childhood experiences, domestic violence, mental health, youth violence, prediction analysis, London knife crime

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Authors: D. ChobfroushKhoei, S. K. Heidari , Sh. Dariadel

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Carbon nanotubes were used in medical sciences especially in drug delivery system and cancer therapy. In this study, we functionalized carboxylated single-wall carbon nanotubes (SWNT-COOH) with 2-en 4-hydroxy cyclo 1-octanon. Synthesized sample was characterized by FT-IR, Raman spectroscopy, SEM, TGA and cellular investigations. The results showed well formation of SWNT-Ester. Cell viability assay results and microscopic observations demonstrated that cancerous cells were killed in the sample. The synthesized sample can be used as a toxic material for cancer therapy.

Keywords: MWNT-COOH, functionalization, phenylisocyanate, phenylisothiocyanate, 1, 4-phenylendiamine, toxicity investigation

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Authors: Serkan Caliskan

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The aim of this study is to understand the spin-resolved properties of ZnO armchair and zigzag nanoribbons. The spin polarization can be induced by either geometry of the nanoribbons or ferromagnetic electrodes. Hence, spin-dependent behavior is revealed in these nanostructures in the absence of external magnetic field. Both electronic structure and magnetic properties of the nanoribbons are analyzed, employing first-principles calculations through Density Functional Theory. The relevant properties using the spin-dependent band structure, conductance, transmission, density of states and magnetic moment are elucidated. These results can be utilized to describe the nanoscale structures and stimulate the experimental works.

Keywords: first principles, spin polarized transport, ZnO device, ZnO nanoribbons

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Authors: Carlos Fontanillas

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Brazil is going through a real revolution in the logistics area. It is increasingly common to find articles and news in this context, as companies begin to become aware that a good management of the areas that make up the logistics can bring excellent results in reducing costs and increasing productivity. With this, companies are investing more emphasis on reduced spending on storage and transport of their products to ensure competitiveness. The scope of this work is the analysis of the logistics of a restaurant and materials will be presented the best way to serve the customer, avoiding the interruption of production due to lack of materials; for it will be analyzed the supply chain in terms of acquisition costs, maintenance and service demand.

Keywords: ABC curve, logistic, productivity, supply chain

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Authors: Sourabh Jain, S. S. Jain

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Intelligent transportation system (ITS) is the application of technologies for developing a user–friendly transportation system to extend the safety and efficiency of urban transportation systems in developing countries. These systems involve vehicles, drivers, passengers, road operators, managers of transport services; all interacting with each other and the surroundings to boost the security and capacity of road systems. The goal of urban corridor management using ITS in road transport is to achieve improvements in mobility, safety, and the productivity of the transportation system within the available facilities through the integrated application of advanced monitoring, communications, computer, display, and control process technologies, both in the vehicle and on the road. Intelligent transportation system is a product of the revolution in information and communications technologies that is the hallmark of the digital age. The basic ITS technology is oriented on three main directions: communications, information, integration. Information acquisition (collection), processing, integration, and sorting are the basic activities of ITS. In the paper, attempts have been made to present the endeavor that was made to interpret and evaluate the performance of the 27.4 Km long study corridor having eight intersections and four flyovers. The corridor consisting of six lanes as well as eight lanes divided road network. Two categories of data have been collected such as traffic data (traffic volume, spot speed, delay) and road characteristics data (no. of lanes, lane width, bus stops, mid-block sections, intersections, flyovers). The instruments used for collecting the data were video camera, stop watch, radar gun, and mobile GPS (GPS tracker lite). From the analysis, the performance interpretations incorporated were the identification of peak and off-peak hours, congestion and level of service (LOS) at midblock sections and delay followed by plotting the speed contours. The paper proposed the urban corridor management strategies based on sensors integrated into both vehicles and on the roads that those have to be efficiently executable, cost-effective, and familiar to road users. It will be useful to reduce congestion, fuel consumption, and pollution so as to provide comfort, safety, and efficiency to the users.

Keywords: ITS strategies, congestion, planning, mobility, safety

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Authors: Fatima Doganc, Hakan Goker

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Benzimidazole moiety is an important pharmacophore and privileged structure for the medicinal chemists, since it exhibits various important biological activities. Some clinically used drugs have benzimidazole moiety, such as omeprazole, astemizole, albendazole and domperidone. 2-(4-tert-Butylphenyl)benzimidazole, is a PGC-1α transcriptional regulator shown to have beneficial effects in diabetic mice. We planned to modify the structure of this compound for developing new antidiabetic drug candidates. Hence, a series of guanidino or amidino, benzo/pyrido/pyrimidino-imidazole derivatives were freshly prepared. Mass, 1H-NMR, 13C-NMR, 2D-NMR spectroscopy techniques were used for the new derivatives to clarify their structures and their purity was controlled through the elemental analysis. Antidiabetic activity studies of the synthesized compounds are under the investigation.

Keywords: antidiabetic agents, benzimidazole, imidazopyridine, imidazopyrimidine

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Authors: I. Wiemann, N. Weiß, E. Schlücker, M. Wensing, A. Kölpin

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Chemical storage of hydrogen by liquid organic hydrogen carriers (LOHC) is a very promising alternative to compression or cryogenics. These carriers have high energy density and allow at the same time efficient and safe storage of hydrogen under ambient conditions and without leakage losses. Another benefit of LOHC is the possibility to transport it using already available infrastructure for transport of fossil fuels. Efficient use of LOHC is related to a precise process control, which requires a number of sensors in order to measure all relevant process parameters, for example, to measure the level of hydrogen loading of the carrier. The degree of loading is relevant for the energy content of the storage carrier and represents simultaneously the modification in chemical structure of the carrier molecules. This variation can be detected in different physical properties like viscosity, permittivity or density. Thereby, each degree of loading corresponds to different viscosity values. Conventional measurements currently use invasive viscosity measurements or near-line measurements to obtain quantitative information. Avoiding invasive measurements has several severe advantages. Efforts are currently taken to provide a precise, non-invasive measurement method with equal or higher precision of the obtained results. This study investigates a method for determination of the viscosity of LOHC. Since the viscosity can retroactively derived from the degree of loading, permittivity is a target parameter as it is a suitable for determining the hydrogenation degree. This research analyses the influence of common physical properties on permittivity. The permittivity measurement system is based on a cavity resonator, an electromagnetic resonant structure, whose resonation frequency depends on its dimensions as well as the permittivity of the medium inside. For known resonator dimensions, the resonation frequency directly characterizes the permittivity. In order to determine the dependency of the permittivity on temperature and flow velocity, an experimental setup with heating device and flow test bench was designed. By varying temperature in the range of 293,15 K -393,15 K and flow velocity up to 140 mm/s, corresponding changes in the resonation frequency were measured in the hundredths of the GHz range.

Keywords: liquid organic hydrogen carriers, measurement, permittivity, viscosity., temperature, flow process

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Authors: Tayba Akram

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our main objective of this study is to work on the etiology of liver cirrhosis, to find basic reasons and causes of liver damage, and to find the pattern of liver cirrhosis in hepatic patients either suffering from hepatitis B/C or simple jaundice. We can evaluate medical treatment and the latest trends in patients suffering from liver cirrhosis. We can evaluate the side effects and adverse effects induced by drug therapy used to treat liver cirrhosis. The conclusion is based on the etiology of liver cirrhosis. The most common cause of liver cirrhosis is the viral Hepatitis C virus. Other common causes of liver cirrhosis that are estimated from our research are Hepatitis B virus, Diabetes Mellitus, Ascites, and very rarely found Hepatitis D virus.

Keywords: etiology, liver, cirrhosis, co-morbid diseases

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Authors: Kinnsley Travis, Camerron M. Crowder

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Mapk8ip3 (Mitogen-Activated Protein Kinase 8 Interacting Protein 3) is a gene that codes for the JIP3 protein, which is a part of the JIP scaffolding protein family. This protein is involved in axonal vesicle transport, elongation and regeneration. Variants in the Mapk8ip3 gene are associated with a rare-genetic condition that results in a neurodevelopmental disorder that can cause a range of phenotypes including global developmental delay and intellectual disability. Currently, there are 18 known individuals diagnosed to have sequenced confirmed Mapk8ip3 genetic disorders. This project focuses on examining the impact of a subset of missense patient variants on the Jip3 protein function by overexpressing the mRNA of these variants in a zebrafish knockout model for Jip3. Plasmids containing cDNA with individual missense variants were reverse transcribed, purified, and injected into single-cell zebrafish embryos (Wild Type, Jip3 -/+, and Jip3 -/-). At 6-days post mRNA microinjection, morphological, behavioral, and microscopic phenotypes were examined in zebrafish larvae. Morphologically, we compared the size and shape of the zebrafish during their development over a 5-day period. Total locomotive activity was assessed using the Microtracker assay and patterns of movement over time were examined using the DanioVision assay. Lastly, we used confocal microscopy to examine sensory axons for swelling and shortened length, which are phenotypes observed in the loss-of-function knockout Jip3 zebrafish model. Using these assays during embryonic development, we determined the impact of various missense variants on Jip3 protein function, compared to knockout and wild-type zebrafish embryo models. Variants in the gene Mapk8ip3 cause rare-neurodevelopmental disorders due to an essential role in axonal vesicle transport, elongation and regeneration. A subset of missense variants was examined by overexpressing the mRNA of these variants in a Jip3 knock-out zebrafish. Morphological, behavioral, and microscopic phenotypes were examined in zebrafish larvae. Using these assays, the spectrum of disorders can be phenotypically determined and the impact of variant location can be compared to knockout and wild-type zebrafish embryo models.

Keywords: rare disease, neurodevelopmental disorders, mrna overexpression, zebrafish research

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Authors: Virendra Nath, Vipin Kumar

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Background: TypeII Diabetes mellitus is a foremost health problem worldwide, predisposing to increased mortality and morbidity. Undesirable effects of the current medications have prompted the researcher to develop more potential drug(s) against the disease. The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptors family and take part in a vital role in the regulation of metabolic equilibrium. They can induce or repress genes associated with adipogenesis, lipid, and glucose metabolism. Aims: Investigation of PPARα/γ agonistic hits were screened by hierarchical virtual screening followed by molecular dynamics simulation and knowledge-based structure-activity relation (SAR) analysis using approved PPAR α/γ dual agonist. Methods: The PPARα/γ agonistic activity of compounds was searched by using Maestro through structure-based virtual screening and molecular dynamics (MD) simulation application. Virtual screening of nuclear-receptor ligands was done, and the binding modes with protein-ligand interactions of newer entity(s) were investigated. Further, binding energy prediction, Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit along with the structural comparative analysis of approved PPARα/γ agonists with screened hit was done for knowledge-based SAR. Results and Discussion: The silicone chip-based approach recognized the most capable nine hits and had better predictive binding energy as compared to the reference drug compound (Tesaglitazar). In this study, the key amino acid residues of binding pockets of both targets PPARα/γ were acknowledged as essential and were found to be associated in the key interactions with the most potential dual hit (ChemDiv-3269-0443). Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit and found root mean square deviation (RMSD) stabile around 2Å and 2.1Å, respectively. Frequency distribution data also revealed that the key residues of both proteins showed maximum contacts with a potent hit during the MD simulation of 20 nanoseconds (ns). The knowledge-based SAR studies of PPARα/γ agonists were studied using 2D structures of approved drugs like aleglitazar, tesaglitazar, etc. for successful designing and synthesis of compounds PPARγ agonistic candidates with anti-hyperlipidimic potential.

Keywords: computational, diabetes, PPAR, simulation

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Authors: Yusuke Katayama, Tetsuhisa Kitamura, Kosuke Kiyohara, Sumito Hayashida, Taku Iwami, Takashi Kawamura, Takeshi Shimazu

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Background: Recently, the number of ambulance dispatches has been increasing in Japan and it is, therefore, difficult to accept emergency patients to hospitals smoothly and appropriately because of the limited hospital capacity. To facilitate the request for patient transport by ambulances and hospital acceptance, the emergency information system using information technology has been built up and introduced in various communities. However, its effectiveness has not been insufficiently revealed in Japan. In 2013, we developed a smartphone application system that enables the emergency-medical-service (EMS) personnel to share information about on-scene ambulance and hospital situation. The aim of this study was to assess the introduction effect of this application for EMS system in Osaka City, Japan. Methods: This study was a retrospective study with population-based ambulance records of Osaka Municipal Fire Department. This study period was six years from January 1, 2010 to December 31, 2015. In this study, we enrolled emergency patients that on-scene EMS personnel conducted the hospital selection for them. The main endpoint was difficulty in hospital acceptance at the scene. The definition of difficulty in hospital acceptance at the scene was to make >=5 phone calls by EMS personnel at the scene to each hospital until a decision to transport was determined. The definition of the smartphone application group was emergency patients transported in the period of 2013-2015 after the introduction of this application, and we assessed the introduction effect of smartphone application with multivariable logistic regression model. Results: A total of 600,526 emergency patients for whom EMS personnel selected hospitals were eligible for our analysis. There were 300,131 smartphone application group (50.0%) in 2010-2012 and 300,395 non-smartphone application group (50.0%) in 2013-2015. The proportion of the difficulty in hospital acceptance was 14.2% (42,585/300,131) in the smartphone application group and 10.9% (32,819/300,395) in the non-smartphone application group, and the difficulty in hospital acceptance significantly decreased by the introduction of the smartphone application (adjusted odds ration; 0.730, 95% confidence interval; 0.718-0.741, P<0.001). Conclusions: Sharing information between ambulance and hospital by introducing smartphone application at the scene was associated with decreasing the difficulty in hospital acceptance. Our findings may be considerable useful for developing emergency medical information system with using IT in other areas of the world.

Keywords: difficulty in hospital acceptance, emergency medical service, infomation technology, smartphone application

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Authors: Ahmed Bahieldin, Ahmed Atef, Jamal S. M. Sabir, Nour O. Gadalla, Sherif Edris, Ahmed M. Alzohairy, Nezar A. Radhwan, Mohammed N. Baeshen, Ahmed M. Ramadan, Hala F. Eissa, Sabah M. Hassan, Nabih A. Baeshen, Osama Abuzinadah, Magdy A. Al-Kordy, Fotouh M. El-Domyati, Robert K. Jansen

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Wild salt-tolerant barley (Hordeum spontaneum) is the ancestor of cultivated barley (Hordeum vulgare or H. vulgare). Although the cultivated barley genome is well studied, little is known about genome structure and function of its wild ancestor. In the present study, RNA-Seq analysis was performed on young leaves of wild barley treated with salt (500 mM NaCl) at four different time intervals. Transcriptome sequencing yielded 103 to 115 million reads for all replicates of each treatment, corresponding to over 10 billion nucleotides per sample. Of the total reads, between 74.8 and 80.3% could be mapped and 77.4 to 81.7% of the transcripts were found in the H. vulgare unigene database (unigene-mapped). The unmapped wild barley reads for all treatments and replicates were assembled de novo and the resulting contigs were used as a new reference genome. This resultedin94.3 to 95.3%oftheunmapped reads mapping to the new reference. The number of differentially expressed transcripts was 9277, 3861 of which were uni gene-mapped. The annotated unigene- and de novo-mapped transcripts (5100) were utilized to generate expression clusters across time of salt stress treatment. Two-dimensional hierarchical clustering classified differential expression profiles into nine expression clusters, four of which were selected for further analysis. Differentially expressed transcripts were assigned to the main functional categories. The most important groups were ‘response to external stimulus’ and ‘electron-carrier activity’. Highly expressed transcripts are involved in several biological processes, including electron transport and exchanger mechanisms, flavonoid biosynthesis, reactive oxygen species (ROS) scavenging, ethylene production, signaling network and protein refolding. The comparisons demonstrated that mRNA-Seq is an efficient method for the analysis of differentially expressed genes and biological processes under salt stress.

Keywords: electron transport, flavonoid biosynthesis, reactive oxygen species, rnaseq

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Authors: Alina Beraudi, Simona Catalani, Dalila De Pasquale, Eva Bianconi, Umberto Santoro, Susanna Stea, Pietro Apostoli

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Recently the European Community, in line with the international scientific community such as with the Consensus Statement, has determined to stop the use of metal-on-metal big head stemmed hip prosthesis. Among the factors accounted as responsible for the high failure rates of these hip implants are the release and accumulation of metal ions. Many studies have correlated the presence of these ions, besides other factors, with the induction of oxidative stress response. In our study on 12 subjects, we observed the patient specific capability to eliminate metal ions after revision surgery. While for cobalt all the patients were able to completely excrete cobalt ions within 5-7 months after metal-on-metal bearing removal, for chromium ions it didn’t happen. If on the one hand the toxicokinetic differences between the two types of ions are confirmed by toxicological and occupational studies, on the other hand, this peculiar way of exposition represents a novel and important point of view. Thus, two different approaches were performed to better understand the subject specific capability to transport metal ions (albumin study) and to manage the response to them (heme-oxygenase-1 study): - a mutational screening of ALBUMIN gene was conducted in 30 MoM prosthetic patients resulting in the absence of nucleotidic changes compared with the ALB reference sequence. To this study was also added the analysis of expression of modified albumin protein; - a gene and protein expression study on 44 patients of heme-oxygenase-1, that is one of the most important antioxidant enzyme induced by metallic ions, was performed. This study resulted in no statistically significant differences in the expression of the gene and protein heme-oxygenase-1 between prosthetic and non-prosthetic patients, as well as between patients with high and low ions levels. Our results show that the protein studied (albumin and heme-oxygenase-1) seem to be not involved in determining chromium and cobalt ions level. On the other hand, achromium and cobalt elimination rates are different, but similar in all patients analyzed, suggesting that this process could be not patient-related. We support the importance of researching more about ions transport within the organism once released by hip prosthesis, about the chemical species involved, the districts where they are contained and the mechanisms of elimination, not excluding the existence of a subjective susceptibility to these metals ions.

Keywords: chromium, cobalt, hip prosthesis, individual susceptibility

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Authors: Mouna Hemdi, Jamel bel Hadj Tahar

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The increasing development of multimedia applications requiring the simultaneous transport of several different services contributes to the evolution of the need for very high-speed network. In this paper, we propose an effective solution to achieve the very high speed while retaining elements of the optical transmission channel. So our study focuses on error correcting codes that aim for quality improvement on duty. We present a comparison of the quality of service for single channels and integrating the code BCH, RS and LDPC in order to find the best code in the different conditions of the transmission.

Keywords: code error correction, high speed broadband, optical transmission, information systems security

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Authors: Feng-Sheng Wang, Chao-Ting Cheng

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Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

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Authors: Ahmad Sabry Mohamad, Kai F. Hoettges, Michael Pycraft Hughes

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This study investigates nanowires using Dielectrophoresis (DEP) in non-aqueous suspension of Tin (IV) Oxide (SnO2) nanoparticles dispersed in N,N-dimenthylformamide (DMF). The self assembly of nanowires in DEP impedance spectroscopy can be determined. In this work, dielectrophoretic method was used to measure non-organic molecules for estimating the permittivity and conductivity characteristic of the nanowires. As in aqueous such as salt solution has been dominating the transport of SnO2, which are the wire growth threshold, depend on applied voltage. While DEP assembly of nanowires depend on applied frequency, the applications of dielectrophoretic collection are measured using impedance spectroscopy.

Keywords: dielectrophoresis, impedance spectroscopy, nanowires, N, N-dimenthylformamide, SnO2

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Authors: Gaweł Magdalena, Lipkowska Anna, Olbert Magdalena, Frąckiewicz Ewelina, Librowski Tadeusz, Nowak Gabriel, Pilc Andrzej

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Heme oxygenase-1 (HO-1), also known as heat shock protein 32 (HSP32), has been shown to be implicated in cytoprotection in various organs. Its activation plays a significant role in acute and chronic inflammation, protecting cells from oxidative injury and apoptosis. This inducible isoform of HO catalyzes the first and rate-limiting step in heme degradation to produce equimolar quantities of biologically active products: carbon monoxide (CO), free iron and biliverdin. CO has been reported to possess anti-apoptotic properties. Moreover, it inhibits the production of proinflammatory cytokines and stimulates the synthesis of the anti-inflammatory interleukin-10 (IL-10), as well as promotes vasodilatation at sites of inflammation. The second product of catalytic HO-1 activity, free cytotoxic iron, is promptly sequestered into the iron storage protein ferritin, which lowers the pro-oxidant state of the cell. The third product, biliverdin, is subsequently converted by biliverdin reductase into the bile pigment bilirubin, the most potent endogenous antioxidant among the constituents of human serum, which modulates immune effector functions and suppresses inflammatory response. Furthermore, being one of the so-called stress proteins, HO-1 adaptively responds to different stressors, such as reactive oxygen species (ROS), inflammatory cytokines and heavy metals and thus protects cells against such conditions as ischemia, hemorrhagic shock, heat shock or hypoxia. It is suggested that pharmacologic modulation of HO-1 may represent an effective strategy for prevention of stress and drug-induced gastrointestinal toxicity. HO-1 is constitutively expressed in normal gastric, intestinal and colonic mucosa and up-regulated during inflammation. It has been proven that HO-1 up-regulated by hemin, heme and cobalt-protoporphyrin ameliorates experimental colitis. In addition, the up-regulation of HO-1 partially explains the mechanism of action of 5-aminosalicylic acid (5-ASA), which is used clinically as an anti-colitis agent. In 2009 Ueda et al. has reported for the first time that mucosal protection by Polaprezinc, a chelate compound of zinc and L-carnosine used as an anti-ulcer drug in Japan, is also attributed to induction of HO-1 in the stomach. Since then, inducers of HO-1 are desired subject of research, as they may constitute therapeutically effective anti-ulcer drugs.

Keywords: heme oxygenase-1, gastric lesions, gastroprotection, Polaprezinc

Procedia PDF Downloads 502