Search results for: drug diffusion

Authors: Fatemeh Haghiralsadat, Mohadese Hashemi, Elham Akhoundi Kharanaghi, Mojgan Yazdani, Mahboobe Sharafodini, Omid Javani

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Niosomes are colloidal particles formed from the self-assembly of non-ionic surfactants in aqueous medium resulting in closed bilayer structures. As a consequence of this hydrophilic and hydrophobic structure, niosomes have the capacity to entrap compounds of different solubilities. Niosomes are promising vehicle for drug delivery which protect sensitive drugs and improve the therapeutic index of drugs by restricting their action to target cells. Essential oils are complex mixtures of volatile compounds such as terpenoids, phenol-derived aromatic components that have been used for many biological properties including bactericidal, fungicidal, insecticidal, antioxidant, anti-tyrosinase and other medicinal properties. Encapsulation of essential oils in niosomes can be an attractive method to overcome their limitation such as volatility, easily decomposition by heat, humidity, light, or oxygen. Cuminum cyminum L. (Cumin) is an aromatic plant included in the Apiaceae family and is used to flavor foods, added to fragrances, and for medical preparations which is indigenous to Egypt, the Mediterranean region, Iran and India. The major components of the Cumin oil were reported as cuminaldehyde, γ -terpinene, β-pinene, p-cymene, p-mentha-1, 3-dien-7-al, and p-mentha-1, 4-dien-7-al which provide the antimicrobial and antioxidant activity. The aim of this work was to formulate Cumin essential oil-loaded niosomes to improve water solubility of natural product and evaluate its physico-chemical features and stability. Cumin oil was obtained through steam distillation using a clevenger-type apparatus and GC/MS was applied to identify the main components of the essential oil. Niosomes were prepared by using thin film hydration method and nanoparticles were characterized for particle size, dispersity index, zeta potential, encapsulation efficiency, in vitro release, and morphology.

Keywords: Cuminum cyminum L., Cumin, niosome, essential oil, encapsulation

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Authors: Abdul Mutalib Md Jani, Abdul Hadi Mahmud, Mohd Tajuddin Mohd Ali

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The rapid growth of interest in surface modification of nanostructures materials that exhibit improved structural and functional properties is attracting more researchers. The unique properties of highly ordered nanoporous anodic aluminium oxide (NAAO) membrane have been proposed as a platform for biosensing applications. They exhibit excellent physical and chemical properties with high porosity, high surface area, tunable pore sizes and excellent chemical resistance. In this study, NAAO was functionalized with 3-aminopropyltriethoxysilane (APTES) to prepared silane-modified NAAO. Amine functional groups are formed on the surface of NAAO during silanization and were characterized using Fourier Transform Infrared spectroscopy (FTIR). The synthesis of multi segment of peptide on NAAO surfaces can be realized by changing the surface chemistry of the NAAO membrane via click chemistry. By click reactions, utilizing alkyne terminated with amino group, various peptides tagged on NAAO can be envisioned from chiral natural or unnatural amino acids using standard coupling methods (HOBt, EDCI and HBTU). This strategy seemly versatile since coupling strategy of dipeptide with another amino acids, leading to tripeptide, tetrapeptide or pentapeptide, can be synthesized without purification. When an appropriate terminus is selected, multiple segments of amino acids can be successfully synthesized on the surfaces. The immobilized NAAO should be easily separated from the reaction medium by conventional filtration, thus avoiding complicated purification methods. Herein, we proposed to synthesize multi fragment peptide as a model for capturing and attaching various small biomolecules on NAAO surfaces and can be also applied as biosensing device, drug delivery systems and biocatalyst.

Keywords: nanoporous anodic aluminium oxide, silanization, peptide synthesise, click chemistry

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Authors: Moulay Driss Mellaoui, Khadija Zaki, Khalid Abbiche, Abdallah Imjjad, Rachid Boutiddar, Abdelouahid Sbai, Aaziz Jmiai, Souad El Issami, Al Mokhtar Lamsabhi, Hanane Zejli

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This study presents a comprehensive analysis of six isoxazolidine and isoxazoline derivatives, leveraging a multifaceted approach that combines Density Functional Theory (DFT), AdmetSAR analysis, and molecular docking simulations to explore their electronic, pharmacokinetic, and anticancer properties. Through DFT analysis, using the B3LYP-D3BJ functional and the 6-311++G(d,p) basis set, we optimized molecular geometries, analyzed vibrational frequencies, and mapped Molecular Electrostatic Potentials (MEP), identifying key sites for electrophilic attacks and hydrogen bonding. Frontier Molecular Orbital (FMO) analysis and Density of States (DOS) plots revealed varying stability levels among the compounds, with 1b, 2b, and 3b showing slightly higher stability. Chemical potential assessments indicated differences in binding affinities, suggesting stronger potential interactions for compounds 1b and 2b. AdmetSAR analysis predicted favorable human intestinal absorption (HIA) rates for all compounds, highlighting compound 3b superior oral effectiveness. Molecular docking and molecular dynamics simulations were conducted on isoxazolidine and 4-isoxazoline derivatives targeting the EGFR receptor (PDB: 1JU6). Molecular docking simulations confirmed the high affinity of these compounds towards the target protein 1JU6, particularly compound 3b, among the isoxazolidine derivatives, compound 3b exhibited the most favorable binding energy, with a g score of -8.50 kcal/mol. Molecular dynamics simulations over 100 nanoseconds demonstrated the stability and potential of compound 3b as a superior candidate for anticancer applications, further supported by structural analyses including RMSD, RMSF, Rg, and SASA values. This study underscores the promising role of compound 3b in anticancer treatments, providing a solid foundation for future drug development and optimization efforts.

Keywords: isoxazolines, DFT, molecular docking, molecular dynamic, ADMET, drugs.

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Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

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Authors: Anna Wolowicz, Katarzyna Staszak, Zbigniew Hubicki

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Nowadays heavy metal ions as well as surfactants are widely used throughout the world due to their useful properties. The consequence of such widespread use is their significant production. On the other hand, the increasing demand for surfactants and heavy metal ions results in production of large amounts of wastewaters which are discharged to the environment from mining, metal plating, pharmaceutical, cosmetic, fertilizer, paper, pesticide and electronic industries, pigments producing, petroleum refining and from autocatalyst, fibers, food, polymer industries etc. Heavy metal ions are non-biodegradable in the environment, cable of accumulation in living organisms and organs, toxic and carcinogenic. On the other hand, not only heavy metal ions but also surfactants affect the purity of water and soils. Some of surfactants are also toxic, harmful and dangerous because they are able to penetrate into surface waters causing foaming, blocked diffusion of oxygen from the atmosphere and act as emulsifiers of hydrophobic substances and increase solubility of many the dangerous pollutants. Among surfactants the anionic ones dominate and their share in the global production of surfactants is around 50 ÷ 60%. Due to the negative impact of heavy metals and surfactants on aquatic ecosystems and living organisms, removal and monitoring of their concentration in the environment is extremely important. Surfactants and heavy metal ions removal can be achieved by different biological and physicochemical methods. The adsorption as well as the ion-exchange methods play here a significant role. The aim of this study was heavy metal ions removal from aqueous solutions using different types of ion exchangers in the presence of anionic surfactants. Preliminary studies of copper(II), nickel(II), zinc(II) and cobalt(II) removal from acidic solutions using ion exchangers (Lewatit MonoPlus TP 220, Lewatit MonoPlus SR 7, Purolite A 400 TL, Purolite A 830, Purolite S 984, Dowex PSR 2, Dowex PSR3, Lewatit AF-5) allowed to select the most effective ones for the above mentioned sorbates and then to checking their removal efficiency in the presence of anionic surfactants. As it was found out Lewatit MonoPlus TP 220 of the chelating type, show the highest sorption capacities for copper(II) ions in comparison with the other ion exchangers under discussion, e.g. 9.98 mg/g (0.1 M HCl); 9.12 mg/g (6 M HCl). Moreover, cobalt(II) removal efficiency was the highest in 0.1 M HCl using also Lewatit MonoPlus TP 220 (6.9 mg/g) similar to zinc(II) (9.1 mg/g) and nickiel(II) (6.2 mg/g). As the anionic surfactant sodium dodecyl sulphate (SDS) was used and surfactant parameters such as viscosity (η), density (ρ) and critical micelle concentration (CMC) were obtained: η = 1.13 ± 0,01 mPa·s; ρ = 999.76 mg/cm3; CMC = 2.26 g/cm3. The studies of copper(II) removal from acidic solutions in the presence of SDS of different concentration show negligible effects on copper(II) removal efficiency. The sorption capacity of Cu(II) from 0.1 M acidic solution of 500 mg/L initial concentration was equal to 46.8 mg/g whereas in the presence of SDS 45.3 mg/g (0.1 mg SDS/L), 47.1 mg/g (0.5 mg SDS/L), 46.6 mg/g (1 mg SDS/L).

Keywords: anionic surfactant, heavy metal ions, ion exchanger, removal

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Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal

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Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.

Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling

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Authors: Nyimas Annissa Mutiara Andini

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There are 325,000 children younger than age 15 in the U.S. have epilepsy. In Indonesia, 40% of 3,5 millions cases of epilepsy happens in children. The most common type of epilepsy, which affects 6 out of 10 people with the disorder, is called idiopathic epilepsy and which has no identifiable cause. One of the most commonly used medications in the treatment of this childhood epilepsy is sodium valproate. Administration of sodium valproat in children has a problem to fail. Nearly 60% of pediatric patients known were mildly, moderately, or severely non-adherent with therapy during the first six months of treatment. Many parents or caregiver took far less medication than prescribed, and the treatment-adherence pattern for the majority of patients was established during the first month of treatment. 42% of the patients were almost always given their medications as prescribed but 13% had very poor adherence even in the early weeks and months of treatment. About 7% of patients initially gave the medication correctly 90% of the time, but adherence dropped to around 20% within six months of starting treatment. Over the six months of observation, the total missing of administration is about four out of 14 doses in any given week. This fail can cause the epilepsy to relapse. Whereas, current reported epilepsy disorder were significantly more likely than those never diagnosed to experience depression (8% vs 2%), anxiety (17% vs 3%), attention-deficit/hyperactivity disorder (23% vs 6%), developmental delay (51% vs 3%), autism/autism spectrum disorder (16% vs 1%), and headaches (14% vs 5%) (all P< 0.05). They had a greater risk of limitation in the ability to do things (relative risk: 9.22; 95% CI: 7.56–11.24), repeating a school grade (relative risk: 2.59; CI: 1.52–4.40), and potentially having unmet medical and mental health needs. In the other side, technology can help to make our life easier. One of the technology, that we can use is a mobile application. A mobile app is a software program we can download and access directly using our phone. Indonesians are highly mobile centric. They use, on average, 6.7 applications over a 30 day period. This paper is aimed to describe an application that could help to control a sodium valproat administration in children; we call it as D-Epi app. D-Epi app is a downloadable application that can help parents or caregiver alert by a timer-related application to warn whether it is the time to administer the sodium valproat. It works not only as a standard alarm, but also inform important information about the drug and emergency stuffs to do to children with epilepsy. This application could help parents and caregiver to take care a child with epilepsy in Indonesia.

Keywords: application, children, D-Epi, epilepsy

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Authors: Afroza Parvin, Md. Mahmudul Hasan, Md. Rokunozzaman, Papon Debnath

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The effluents of textile industries have considerable amounts of heavy metals, causing potential microbial metal loads if discharged into the environment without treatment. Aim: In this present study, both lactose and non-lactose fermenting bacterial isolates were isolated from textile industrial effluents of a specific region of Bangladesh, named Savar, to compare and understand the load of heavy metals in these microorganisms determining the effects of heavy metal resistance properties on antibiotic resistance. Methods: Five different textile industrial canals of Savar were selected, and effluent samples were collected in 2016 between June to August. Total bacterial colony (TBC) was counted for day 1 to day 5 for 10-6 dilution of samples to 10-10 dilution. All the isolates were isolated and selected using 4 differential media, and tested for the determination of minimum inhibitory concentration (MIC) of heavy metals and antibiotic susceptibility test with plate assay method and modified Kirby-Bauer disc diffusion method, respectively. To detect the combined effect of heavy metals and antibiotics, a binary exposure experiment was performed, and to understand the plasmid profiling plasmid DNA was extracted by alkaline lysis method of some selective isolates. Results: Most of the cases, the colony forming units (CFU) per plate for 50 ul diluted sample were uncountable at 10-6 dilution, however, countable for 10-10 dilution and it didn’t vary much from canal to canal. A total of 50 Shigella, 50 Salmonella, and 100 E.coli (Escherichia coli) like bacterial isolates were selected for this study where the MIC was less than or equal to 0.6 mM for 100% Shigella and Salmonella like isolates, however, only 3% E. coli like isolates had the same MIC for nickel (Ni). The MIC for chromium (Cr) was less than or equal to 2.0 mM for 16% Shigella, 20% Salmonella, and 17% E. coli like isolates. Around 60% of both Shigella and Salmonella, but only 20% of E.coli like isolates had a MIC of less than or equal to 1.2 mM for lead (Pb). The most prevalent resistant pattern for azithromycin (AZM) for Shigella and Salmonella like isolates was found 38% and 48%, respectively; however, for E.coli like isolates, the highest pattern (36%) was found for sulfamethoxazole-trimethoprim (SXT). In the binary exposure experiment, antibiotic zone of inhibition was mostly increased in the presence of heavy metals for all types of isolates. The highest sized plasmid was found 21 Kb and 14 Kb for lactose and non-lactose fermenting isolates, respectively. Conclusion: Microbial resistance to antibiotics and metal ions, has potential health hazards because these traits are generally associated with transmissible plasmids. Microorganisms resistant to antibiotics and tolerant to metals appear as a result of exposure to metal-contaminated environments.

Keywords: antibiotics, effluents, heavy metals, minimum inhibitory concentration, resistance

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Authors: M. Naimi, M. B. Khaled

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The aim of the present work was to test in vitro inhibition of food pathogens and spoilage bacteria by crude bacteriocins from autochthonous lactic acid bacteria. Thirty autochthonous lactic acid bacteria isolated previously, belonging to the genera: Lactobacillus, Carnobacterium, Lactococcus, Vagococcus, Streptococcus, and Pediococcus, have been screened by an agar spot test and a well diffusion assay against Gram-positive and Gram-negative harmful bacteria: Bacillus cereus, Bacillus subtilis ATCC 6633, Escherichia coli ATCC 8739, Salmonella typhimurium ATCC 14028, Staphylococcus aureus ATCC 6538, and Pseudomonas aeruginosa under conditions means to reduce lactic acid and hydrogen peroxide effect to select bacteria with high bacteriocinogenic potential. Furthermore, crude bacteriocins semiquantification and heat sensitivity to different temperatures (80, 95, 110°C, and 121°C) were performed. Another exploratory test concerning the response of St. aureus ATCC 6538 to the presence of crude bacteriocins was realized. It has been observed by the agar spot test that fifteen candidates were active toward Gram-positive targets strains. The secondary screening demonstrated an antagonistic activity oriented only against St. aureus ATCC 6538, leading to the selection of five isolates: Lm14, Lm21, Lm23, Lm24, and Lm25 with a larger inhibition zone compared to the others. The ANOVA statistical analysis reveals a small variation of repeatability: Lm21: 0.56%, Lm23: 0%, Lm25: 1.67%, Lm14: 1.88%, Lm24: 2.14%. Conversely, slight variation was reported in terms of inhibition diameters: 9.58± 0.40, 9.83± 0.46, and 10.16± 0.24 8.5 ± 0.40 10 mm for, Lm21, Lm23, Lm25, Lm14and Lm24, indicating that the observed potential showed a heterogeneous distribution (BMS = 0.383, WMS = 0.117). The repeatability coefficient calculated displayed 7.35%. As for the bacteriocins semiquantification, the five samples exhibited production amounts about 4.16 for Lm21, Lm23, Lm25 and 2.08 AU/ml for Lm14, Lm24. Concerning the sensitivity the crude bacteriocins were fully insensitive to heat inactivation, until 121°C, they preserved the same inhibition diameter. As to, kinetic of growth , the µmax showed reductions in pathogens load for Lm21, Lm23, Lm25, Lm14, Lm24 of about 42.92%, 84.12%, 88.55%, 54.95%, 29.97% in the second trails. Inversely, this pathogen growth after five hours displayed differences of 79.45%, 12.64%, 11.82%, 87.88%, 85.66% in the second trails, compared to the control. This study showed potential inhibition to the growth of this food pathogen, suggesting the possibility to improve the hygienic food quality.

Keywords: exploratory test, lactic acid bacteria, crude bacteriocins, spoilage, pathogens

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Authors: Kaushik Vaideeswaran, Jean Gobet, Patrick Margraf, Olha Sereda

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Nitrocarburisation is a surface hardening technique often applied to improve the wear resistance of steel surfaces. It is considered to be a promising solution in comparison with other processes such as flame spraying, owing to the formation of a diffusion layer which provides mechanical integrity, as well as its cost-effectiveness. To improve other tribological properties of the surface such as the coefficient of friction (COF), dry lubricants are utilized. Currently, the lifetime of steel components in many applications using either of these techniques individually are faced with the limitations of the two: high COF for nitrocarburized surfaces and low wear resistance of dry lubricant coatings. To this end, the current study involves the creation of a hybrid surface using the impregnation of a dry lubricant on to a nitrocarburized surface. The mechanical strength and hardness of Gerster SA’s nitrocarburized surfaces accompanied by the impregnation of the porous outermost layer with a solid lubricant will create a hybrid surface possessing both outstanding wear resistance and a low friction coefficient and with high adherence to the substrate. Gerster SA has the state-of-the-art technology for the surface hardening of various steels. Through their expertise in the field, the nitrocarburizing process parameters (atmosphere, temperature, dwelling time) were optimized to obtain samples that have a distinct porous structure (in terms of size, shape, and density) as observed by metallographic and microscopic analyses. The porosity thus obtained is suitable for the impregnation of a dry lubricant. A commercially available dry lubricant with a thermoplastic matrix was employed for the impregnation process, which was optimized to obtain a void-free interface with the surface of the nitrocarburized layer (henceforth called hybrid surface). In parallel, metallic samples without nitrocarburisation were also impregnated with the same dry lubricant as a reference (henceforth called reference surface). The reference and the nitrocarburized surfaces, with and without the dry lubricant were tested for their tribological behavior by sliding against a quenched steel ball using a nanotribometer. Without any lubricant, the nitrocarburized surface showed a wear rate 5x lower than the reference metal. In the presence of a thin film of dry lubricant ( < 2 micrometers) and under the application of high loads (500 mN or ~800 MPa), while the COF for the reference surface increased from ~0.1 to > 0.3 within 120 m, the hybrid surface retained a COF < 0.2 for over 400m of sliding. In addition, while the steel ball sliding against the reference surface showed heavy wear, the corresponding ball sliding against the hybrid surface showed very limited wear. Observations of the sliding tracks in the hybrid surface using Electron Microscopy show the presence of the nitrocarburized nodules as well as the lubricant, whereas no traces of the lubricant were found in the sliding track on the reference surface. In this manner, the clear advantage of combining nitrocarburisation with the impregnation of a dry lubricant towards forming a hybrid surface has been demonstrated.

Keywords: dry lubrication, hybrid surfaces, improved wear resistance, nitrocarburisation, steels

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Authors: Paula Quiterio, Arlete Apolinario, Celia T. Sousa, Joao Azevedo, Paula Dias, Adelio Mendes, Joao P. Araujo

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Nowadays one of the mankind's greatest challenges has been the supply of low-cost and environmentally friendly energy sources as an alternative to non-renewable fossil fuels. Hydrogen has been considered a promising solution, representing a clean and low-cost fuel. It can be produced directly from clean and abundant resources, such as sunlight and water, using photoelectrochemical cells (PECs), in a process that mimics the nature´s photosynthesis. Hematite (alpha-Fe2O3) has attracted considerable attention as a promising photoanode for solar water splitting, due to its high chemical stability, nontoxicity, availability and low band gap (2.2 eV), which allows reaching a high thermodynamic solar-to-hydrogen efficiency of 16.8 %. However, the main drawbacks of hematite such as the short hole diffusion length and the poor conductivity that lead to high electron-hole recombination result in significant PEC efficiency losses. One strategy to overcome these limitations and to increase the PEC efficiency is to use 1D nanostructures, such as nanotubes (NTs) and nanowires (NWs), which present high aspect ratios and large surface areas providing direct pathways for electron transport up to the charge collector and minimizing the recombination losses. In particular, due to the ultrathin walls of the NTs, the holes can reach the surface faster than in other nanostructures, representing a key factor for the NTs photoresponse. In this work, we prepared hematite NWs and NTs, respectively by hydrothermal process and electrochemical anodization. For hematite NWs growing, we studied the effect of variable hydrothermal conditions, different annealing temperatures and time, and the use of Ti and Sn dopants on the morphology and PEC performance. The crystalline phase characterization by X-ray diffraction was crucial to distinguish the formation of hematite and other iron oxide phases, alongside its effect on the photoanodes conductivity and consequent PEC efficiency. The conductivity of the as-prepared NWs is very low, in the order of 10-5 S cm-1, but after doping and annealing optimization it increased by a factor of 105. A high photocurrent density of 1.02 mA cm-2 at 1.45 VRHE was obtained under simulated sunlight, which is a very promising value for this kind of hematite nanostructures. The stability of the photoelectrodes was also tested, presenting good stability after several J-V measurements over time. The NTs, synthesized by fast anodizations with potentials ranging from 20-100 V, presented a linear growth of the NTs pore walls, with very low thicknesses from 10 - 18 nm. These preliminary results are also very promising for the use of hematite photoelectrodes on PEC hydrogen applications.

Keywords: hematite, nanotubes, nanowires, photoelectrochemical cells

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Authors: Simon Nyarko

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This study examined the microbial flora contamination of the Ghanaian paper currency notes and antibiotic resistance in Ejura Municipal, Ashanti Region, Ghana. This is a descriptive cross-sectional study designed to assess the profile of microflora contamination of the Ghanaian paper currency notes and antibiotic-resistant in the Ejura Municipality. The research was conducted in Ejura, a town in the Ejura Sekyeredumase Municipal of the Ashanti region of Ghana. 70 paper currency notes which were freshly collected from the bank, consisting of 15 pieces of GH ¢1, GH ¢2, and GH ¢5, 10 pieces of GH ¢10 and GH ¢20, and 5 pieces of GH ¢50, were randomly sampled from people by exchanging their money in usage with those freshly secured from the bank. The surfaces of each GH¢ note were gently swabbed and sent to the lab immediately in sterile Zip Bags and sealed, and tenfold serial dilution was inoculated on plate count agar (PCA), MacConkey agar (MCA), mannitol salt agar (MSA), and deoxycholate citrate agar (DCA). For bacterial identification, the study used appropriate laboratory and biochemical tests. The data was analyzed using SPSS-IBM version 20.0. It was found that 95.2 % of the 70 GH¢ notes tested positive for one or more bacterial isolates. On each GH¢ note, mean counts on PCA ranged from 3.0 cfu/ml ×105 to 4.8 cfu/ml ×105. Of 124 bacteria isolated. 36 (29.03 %), 32 (25.81%), 16 (12.90 %), 20 (16.13%), 13 (10.48 %), and 7 (5.66 %) were from GH¢1, GH¢2, GH¢10, GH¢5, GH¢20, and GH¢50, respectively. Bacterial isolates were Escherichia coli (25.81%), Staphylococcus aureus (18.55%), coagulase-negative Staphylococcus (15.32%), Klebsiella species (12.10%), Salmonella species (9.68%), Shigella species (8.06%), Pseudomonas aeruginosa (7.26%), and Proteus species (3.23%). Meat shops, commercial drivers, canteens, grocery stores, and vegetable shops contributed 25.81 %, 20.16 %, 19.35 %, 17.74 %, and 16.94 % of GH¢ notes, respectively. There was 100% resistance of the isolates to Erythromycin (ERY), and Cotrimoxazole (COT). Amikacin (AMK) was the most effective among the antibiotics as 75% of the isolates were susceptible to it. This study has demonstrated that the Ghanaian paper currency notes are heavily contaminated with potentially pathogenic bacteria that are highly resistant to the most widely used antibiotics and are a threat to public health.

Keywords: microflora, antibiotic resistance, staphylococcus aureus, culture media, multi-drug resistance

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Authors: Dong-Gi Lee, Suyeon Cha, Yong-Sun Bahn

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Sterol lipid is essential for cell membrane structure in eukaryotic cells. In mammalian cells, sterol regulatory element binding proteins (SREBPs) act as principal regulators of cellular cholesterol which is essential for proper cell membrane fluidity and structure. SREBP and sterol regulation are related to levels of cellular oxygen because it is a major substrate for sterol synthesis. Upon cellular sterol and oxygen levels are depleted, SREBP is translocated to the Golgi where it undergoes proteolytic cleavage of N terminus, then it travels to the nucleus to play a role as transcription factor. In yeast cells, synthesis of ergosterol is also highly oxygen consumptive, and Sre1 is a transcription factor known to play a central role in adaptation to growth under low oxygen condition and sterol homeostasis in Cryptococcus neoformans. In this study, we observed phenotypes in other strains of Cryptococcus species by constructing hob1Δ and sre1Δ mutants to confirm whether the functions of both genes are conserved in most serotypes. As a result, hob1Δ showed no noticeable phenotype under treatment of antifungal drugs and most environmental stresses in R265 (C. gattii) and XL280 (C. neoformans), suggesting that Hob1 is related to sterol regulation only in H99 (serotype A). On the other hand, the function of Sre1 was found to be conserved in most serotypes. Furthermore, mating experiment of hob1Δ or sre1Δ showed dramatic defects in serotype A (H99) and D (XL280). It revealed that Hob1 and Sre1 related to mating ability in Cryptococcus species, especially cell fusion efficiency. In conclusion, HOB1 and SRE1 play crucial role in regulating sterol-homeostasis and differentiation in C. neoformans, moreover, Hob1 is specific gene in Cryptococcus neoformans. It suggests that Hob1 is considered as potent factor-targeted new safety antifungal drug.

Keywords: cryptococcus neoformans, Hob1, Sre1, sterol regulatory element binding proteins

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Authors: Grace McCambridge, Alanna Keady, Madhur Agrawal, Dequina Nicholas Alvarado, Barbara Nikolajczyk, Leena Panneerseelan-Bharath

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Age is a non-modifiable risk factor for the inflammation that underlies pathologies such as type 2 diabetes mellitus (T2DM). Inflammation, as indicated by circulating cytokines, rises in aging, but mechanisms that promote this ‘inflammaging’ remain poorly defined. Furthermore, downstream consequences of inflammaging, including the development of an inflammatory profile that predicts comorbidities like T2DM, remain speculative. We tested the possibility that natural aging-associated changes in autophagy, a process that is compromised in both aging and T2DM, regulates inflammatory profiles in older subjects. Our data showed that circulating CD4⁺ T cells from older compared to younger subjects have (i) defects in autophagy; (ii) higher mitochondria accumulation; (iii) a failure to metabolically shift from oxidative phosphorylation to anaerobic glycolysis upon αCD3/CD28 activation; (iv) more reactive oxygen species (ROS) accumulation; and (v) a cytokine profile that recapitulates the Th17 profile that predicts T2DM. ROS scavenging in cells from older subjects restored mitochondrial mass and membrane potential (indicators of improved autophagy) and reduced Th17 cytokines to amounts made by T cells from younger subjects. Knock-down of the autophagy protein Atg3 in T cells from younger subjects increased mitochondrial accumulation and Th17 cytokines. To begin translating these findings to clinical practice, we showed that physiological concentrations of the diabetes drug metformin (100 µM) added in vitro enhanced autophagy, prevented mitochondria and ROS accumulation, increased anaerobic glycolysis, and decreased Th17 cytokines in activated CD4⁺ T cells from older subjects. Metformin therefore improves autophagy and multiple downstream pro-inflammatory mechanisms CD4⁺ T cells from older subjects. We conclude that autophagy improvement ameliorates the development of a T2DM-predictive Th17 profile in aging, and thus holds promise for delay or prevention of aging-associated metabolic decline.

Keywords: autophagy, mitochondrial turnover, ROS, glycolysis

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Authors: Abdullah Faqihi, John Hedley

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Biosensors play a significant role in the healthcare sectors, scientific and technological progress. Developing electrodes that are easy to manufacture and deliver better electrochemical performance is advantageous for diagnostics and biosensing. They can be implemented extensively in various analytical tasks such as drug discovery, food safety, medical diagnostics, process controls, security and defence, in addition to environmental monitoring. Development of biosensors aims to create high-performance electrochemical electrodes for diagnostics and biosensing. A biosensor is a device that inspects the biological and chemical reactions generated by the biological sample. A biosensor carries out biological detection via a linked transducer and transmits the biological response into an electrical signal; stability, selectivity, and sensitivity are the dynamic and static characteristics that affect and dictate the quality and performance of biosensors. In this research, a developed experimental study for laser scribing technique for graphene oxide inside a vacuum chamber for processing of graphene oxide is presented. The processing of graphene oxide (GO) was achieved using the laser scribing technique. The effect of the laser scribing on the reduction of GO was investigated under two conditions: atmosphere and vacuum. GO solvent was coated onto a LightScribe DVD. The laser scribing technique was applied to reduce GO layers to generate rGO. The micro-details for the morphological structures of rGO and GO were visualised using scanning electron microscopy (SEM) and Raman spectroscopy so that they could be examined. The first electrode was a traditional graphene-based electrode model, made under normal atmospheric conditions, whereas the second model was a developed graphene electrode fabricated under a vacuum state using a vacuum chamber. The purpose was to control the vacuum conditions, such as the air pressure and the temperature during the fabrication process. The parameters to be assessed include the layer thickness and the continuous environment. Results presented show high accuracy and repeatability achieving low cost productivity.

Keywords: laser scribing, lightscribe DVD, graphene oxide, scanning electron microscopy

Procedia PDF Downloads 98

Authors: Suruchi Saini, Hitender Kumar Tyagi

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With the rapid progress of the nanotechnology industry, it is becoming increasingly important to have compact semiconductor devices to function and offer the best results at various technology nodes. While performing the scaling of the device, several short-channel effects occur. To minimize these scaling limitations, some device architectures have been developed in the semiconductor industry. FinFET is one of the most promising structures. Also, the double-gate 2D Fin field effect transistor has the benefit of suppressing short channel effects (SCE) and functioning well for less than 14 nm technology nodes. In the present research, the MuGFET simulation tool is used to analyze and explain the electrical behaviour of a double-gate 2D Fin field effect transistor. The drift-diffusion and Poisson equations are solved self-consistently. Various models, such as Fermi-Dirac distribution, bandgap narrowing, carrier scattering, and concentration-dependent mobility models, are used for device simulation. The transfer and output characteristics of the double-gate 2D Fin field effect transistor are determined at 10 nm technology node. The performance parameters are extracted in terms of threshold voltage, trans-conductance, leakage current and current on-off ratio. In this paper, the device performance is analyzed at different structure parameters. The utilization of the Id-Vg curve is a robust technique that holds significant importance in the modeling of transistors, circuit design, optimization of performance, and quality control in electronic devices and integrated circuits for comprehending field-effect transistors. The FinFET structure is optimized to increase the current on-off ratio and transconductance. Through this analysis, the impact of different channel widths, source and drain lengths on the Id-Vg and transconductance is examined. Device performance was affected by the difficulty of maintaining effective gate control over the channel at decreasing feature sizes. For every set of simulations, the device's features are simulated at two different drain voltages, 50 mV and 0.7 V. In low-power and precision applications, the off-state current is a significant factor to consider. Therefore, it is crucial to minimize the off-state current to maximize circuit performance and efficiency. The findings demonstrate that the performance of the current on-off ratio is maximum with the channel width of 3 nm for a gate length of 10 nm, but there is no significant effect of source and drain length on the current on-off ratio. The transconductance value plays a pivotal role in various electronic applications and should be considered carefully. In this research, it is also concluded that the transconductance value of 340 S/m is achieved with the fin width of 3 nm at a gate length of 10 nm and 2380 S/m for the source and drain extension length of 5 nm, respectively.

Keywords: current on-off ratio, FinFET, short-channel effects, transconductance

Procedia PDF Downloads 49

Authors: Sohan Sengupta, Arnab Pramanik, Abhrajyoti Ghosh, Maitree Bhattacharyya

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Newly emerged phyto-pathogens and multi drug resistance have been threating the world for last few decades. Actinomycetes, the most endowed group of microorganisms isolated from unexplored regions of the world may be the ultimate solution to these problems. Thus the aim of this study was to isolate several bioactive actinomycetes strains capable of producing antimicrobial secondary metabolite from Sundarbans, the only mangrove tiger land of the world. Fifty four actinomycetes were isolated and analyzed for antimicrobial activity against fifteen test organisms including three phytopathogens. Nine morphologically distinct and biologically active isolates were subjected to polyphasic identification study. 16s rDNA sequencing indicated eight isolates to reveal maximum similarity to the genus streptomyces, whereas one isolate presented only 93.57% similarity with Streptomyces albogriseolus NRRL B-1305T. Seventy-one carbon sources and twenty-three chemical sources utilization assay revealed their metabolic relatedness. Among these nine isolates three specific strains were found to have notably higher degree of antimicrobial potential effective in a broader range including phyto-pathogenic fungus. PCR base whole genome screen for PKS and NRPS genes, confirmed the occurrence of bio-synthetic gene cluster in some of the isolates for novel antibiotic production. Finally the strain SMS_SU21, which showed antimicrobial activity with MIC value of 0.05 mg ml-1and antioxidant activity with IC50 value of 0.242±0.33 mg ml-1 was detected to be the most potential one. True prospective of this strain was evaluated utilizing GC-MS and the bioactive compound responsible for antimicrobial activity was purified and characterized. Rare bioactive actinomycetes were isolated from unexplored heritage site. Diversity of the biosynthetic gene cluster for antimicrobial compound production has also been evaluated. Antimicrobial compound SU21-C has been identified and purified which is active against a broad range of pathogens.

Keywords: actinomycetes, sundarbans, antimicrobial, pks nrps, phyto-pathogens, GC-MS

Procedia PDF Downloads 488

Authors: Marina Arino Martin, John McEvoy, Eakalak Khan

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Endoxifen is an active metabolite responsible for the effectiveness of tamoxifen, a chemotherapeutic drug widely used for endocrine responsive breast cancer and chemo-preventive long-term treatment. Tamoxifen and endoxifen are not completely metabolized in human body and are actively excreted. As a result, they are released to the water environment via wastewater treatment plants (WWTPs). The presence of tamoxifen in the environment produces negative effects on aquatic lives due to its antiestrogenic activity. Because endoxifen is 30-100 times more potent than tamoxifen itself and also presents antiestrogenic activity, its presence in the water environment could result in even more toxic effects on aquatic lives compared to tamoxifen. Data on actual concentrations of endoxifen in the environment is limited due to recent discovery of endoxifen pharmaceutical activity. However, endoxifen has been detected in hospital and municipal wastewater effluents. The detection of endoxifen in wastewater effluents questions the treatment efficiency of WWTPs. Studies reporting information about endoxifen removal in WWTPs are also scarce. There was a study that used chlorination to eliminate endoxifen in wastewater. However, an inefficient degradation of endoxifen by chlorination and the production of hazardous disinfection by-products were observed. Therefore, there is a need to remove endoxifen from wastewater prior to chlorination in order to reduce the potential release of endoxifen into the environment and its possible effects. The aim of this research is to isolate and identify bacteria strain(s) capable of degrading endoxifen into less hazardous compound(s). For this purpose, bacteria strains from WWTPs were exposed to endoxifen as a sole carbon and nitrogen source for 40 days. Bacteria presenting positive growth were isolated and tested for endoxifen biodegradation. Endoxifen concentration and by-product formation were monitored. The Monod kinetic model was used to determine endoxifen biodegradation rate. Preliminary results of the study suggest that isolated bacteria from WWTPs are able to growth in presence of endoxifen as a sole carbon and nitrogen source. Ongoing work includes identification of these bacteria strains and by-product(s) of endoxifen biodegradation.

Keywords: biodegradation, bacterial degraders, endoxifen, wastewater

Procedia PDF Downloads 197

Authors: Michael Huber, Maximilian J. Poller, Jens Tochtermann, Wolfgang Korth, Andreas Jess, Jakob Albert

Abstract:

Aside from the desulfurisation, the denitrogenation of fuels is of great importance to minimize the environmental impact of transport emissions. The oxidative reaction pathway of organic nitrogen in the catalytic oxidative denitrogenation could be successfully elucidated. This is the first time such a pathway could be traced in detail in non-microbial systems. It was found that the organic nitrogen is first oxidized to nitrate, which is subsequently reduced to molecular nitrogen via nitrous oxide. Hereby, the organic substrate serves as a reducing agent. The discovery of this pathway is an important milestone for the further development of fuel denitrogenation technologies. The United Nations aims to counteract global warming with Net Zero Emissions (NZE) commitments; however, it is not yet foreseeable when crude oil-based fuels will become obsolete. In 2021, more than 50 million barrels per day (mb/d) were consumed for the transport sector alone. Above all, heteroatoms such as sulfur or nitrogen produce SO₂ and NOx during combustion in the engines, which is not only harmful to the climate but also to health. Therefore, in refineries, these heteroatoms are removed by hy-drotreating to produce clean fuels. However, this catalytic reaction is inhibited by the basic, nitrogenous reactants (e.g., quinoline) as well as by NH3. The ion pair of the nitrogen atom forms strong pi-bonds to the active sites of the hydrotreating catalyst, which dimin-ishes its activity. To maximize the desulfurization and denitrogenation effectiveness in comparison to just extraction and adsorption, selective oxidation is typically combined with either extraction or selective adsorption. The selective oxidation produces more polar compounds that can be removed from the non-polar oil in a separate step. The extraction step can also be carried out in parallel to the oxidation reaction, as a result of in situ separation of the oxidation products (ECODS; extractive catalytic oxidative desulfurization). In this process, H8PV5Mo7O40 (HPA-5) is employed as a homogeneous polyoxometalate (POM) catalyst in an aqueous phase, whereas the sulfur containing fuel components are oxidized after diffusion from the organic fuel phase into the aqueous catalyst phase, to form highly polar products such as H₂SO₄ and carboxylic acids, which are thereby extracted from the organic fuel phase and accumulate in the aqueous phase. In contrast to the inhibiting properties of the basic nitrogen compounds in hydrotreating, the oxidative desulfurization improves with simultaneous denitrification in this system (ECODN; extractive catalytic oxidative denitrogenation). The reaction pathway of ECODS has already been well studied. In contrast, the oxidation of nitrogen compounds in ECODN is not yet well understood and requires more detailed investigations.

Keywords: oxidative reaction pathway, denitrogenation of fuels, molecular catalysis, polyoxometalate

Procedia PDF Downloads 159

Authors: Rolivhuwa Bishop Ramagoma1*, Lynn Cairncross1, , Saartjie Roux1

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According to the world health organisation, colon cancer is among the most common cancers diagnosed in both men and women. Specifically, it is the second leading cause of cancer related deaths accounting for over 860 000 deaths worldwide in 2018. Currently, chemotherapy has become an essential component of most cancer treatments. Despite progress in cancer drug development over the previous years, traditional chemotherapeutic drugs still have low selectivity for targeting tumour tissues and are frequently constrained by dose-limiting toxicity. The creation of nanoscale delivery vehicles capable of directly directing treatment into cancer cells has recently caught the interest of researchers. Herein, the development of peptide-functionalized polyethylene glycol gold nanoparticles (Peptide-PEG-AuNPs) as a cellular probe and delivery agent is described, with the higher aim to develop a specific diagnostic prototype and assess their specificity not only against cell lines but primary human cells as well. Gold nanoparticles (AuNPs) were synthesized and stabilized through chemical conjugation. The synthesized AuNPs were characterized, stability in physiological solutions was assessed, their cytotoxicity against colon carcinoma and non-carcinoma skin fibroblasts was also studied. Furthermore, genetic effect through real-time polymerase chain reaction (RT-PCR), localization and uptake, peptide specificity were also determined. In this study, different peptide-AuNPs were found to have preferential toxicity at higher concentrations, as revealed by cell viability assays, however, all AuNPs presented immaculate stability for over 3 months following the method of synthesis. The final obtained peptide-PEG-AuNP conjugates showed good biocompatibility in the presence of high ionic solutions and biological media and good cellular uptake. Formulation of colon cancer specific targeting peptide was successful, additionally, the genes/pathways affected by the treatments were determined through RT-PCR. Primary cells study is still on going with promising results thus far.

Keywords: nanotechnology, cancer, diagnosis, therapeutics, gold nanoparticles.

Procedia PDF Downloads 66

Authors: Ben Main Piotr Ozieranski

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State government spending on pharmaceuticals stands at 1 trillion USD globally, promoting criticism of the pharmaceutical industry's monetization of drug efficacy, product cost overvaluation, and health injustice. This paper elucidates the mechanisms behind a state-institutional response to this problem through the sociological lens of the strategic relational approach to state power. To do so, 30 expert interviews, legal and policy documents are drawn on to explain how state elites in New Zealand have successfully contested a 30-year “pharmaceutical spending containment policy”. Proceeding from Jessop's notion of strategic “selectivity”, encompassing analyses of the enabling features of state actors' ability to harness state structures, a theoretical explanation is advanced. First, a strategic context is described that consists of dynamics around pharmaceutical dealmaking between the state bureaucracy, pharmaceutical pricing strategies (and their effects), and the industry. Centrally, the pricing strategy of "bundling" -deals for packages of drugs that combine older and newer patented products- reflect how state managers have instigated an “incentivization game” that is played by state and industry actors, including HTA professionals, over pharmaceutical products (both current and in development). Second, a protective context is described that is comprised of successive legislative-judicial responses to the strategic context and characterized by the regulation and the societalisation of commercial law. Third, within the policy, the achievement of increased pharmaceutical coverage (pharmaceutical “mix”) alongside contained spending is conceptualized as a state defence of a "social profit". As such, in contrast to scholarly expectations that political and economic cultures of neo-liberalism drive pharmaceutical policy-making processes, New Zealand's state elites' approach is shown to be antipathetic to neo-liberals within an overall capitalist economy. The paper contributes an analysis of state pricing strategies and how they are embedded in state regulatory structures. Additionally, through an analysis of the interconnections of state power and pharmaceutical value Abrahams's neo-liberal corporate bias model for pharmaceutical policy analysis is problematised.

Keywords: pharmaceutical governance, pharmaceutical bureaucracy, pricing strategies, state power, value theory

Procedia PDF Downloads 54

Authors: J. N. Nackler, K. Saleh Pascha, W. Winter

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WHISCERS™ (Whole House In-Situ Carbon and Energy Reduction Solution) is an innovative process for Internal Wall Insulation (IWI) for energy-efficient retrofitting of heritage building, which uses laser measuring to determine the dimensions of a room, off-site insulation board cutting and rapid installation to complete the process. As part of a multinational investigation consortium the Austrian part adapted the WHISCERS system to local conditions of Vienna where most historical buildings have valuable stucco facades, precluding the application of an external insulation. The Austrian project contribution addresses the replacement of commonly used extruded polystyrene foam (XPS) with renewable materials such as wood and wood products to develop a more sustainable IWI system. As the timber industry is a major industry in Austria, a new innovative and more sustainable IWI solution could also open up new markets. The first approach of investigation was the Life Cycle Assessment (LCA) to define the performance of wood fibre board as insulation material in comparison to normally used XPS-boards. As one of the results the global-warming potential (GWP) of wood-fibre-board is 15 times less the equivalent to carbon dioxide while in the case of XPS it´s 72 times more. The hygrothermal simulation program WUFI was used to evaluate and simulate heat and moisture transport in multi-layer building components of the developed IWI solution. The results of the simulations prove in examined boundary conditions of selected representative brickwork constructions to be functional and usable without risk regarding vapour diffusion and liquid transport in proposed IWI. In a further stage three different solutions were developed and tested (1 - glued/mortared, 2 - with soft board, connected to wall with gypsum board as top layer, 3 - with soft board and clay board as top layer). All three solutions presents a flexible insulation layer out of wood fibre towards the existing wall, thus compensating irregularities of the wall surface. From first considerations at the beginning of the development phase, three different systems had been developed and optimized according to assembly technology and tested as small specimen in real object conditions. The built prototypes are monitored to detect performance and building physics problems and to validate the results of the computer simulation model. This paper illustrates the development and application of the Internal Wall Insulation system.

Keywords: internal insulation, wood fibre, hygrothermal simulations, monitoring, clay, condensate

Procedia PDF Downloads 203

Authors: M. S. Raza, A. Kapil, Sonu Tyagi, H. Gautam, S. Mohapatra, R. Chaudhry, S. Sood, V. Goyal, R. Lodha, V. Sreenivas, B. K. Das

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Background: Acute bacterial meningitis remains the major cause of mortality and morbidity. More than half of the survivors develop the significant lifelong neurological abnormalities. Diagnosis of the hospital acquired acute bacterial meningitis (HAABM) is challenging as it appears either in the post operative patients or patients acquire the organisms from the hospital environment. In both the situations, pathogens are exposed to high dose of antibiotics. Chances of getting multidrug resistance organism are very high. We have performed this experiment to find out the etiological agents of HAABM and its antibiotics susceptibility pattern. Methodology: A perspective study was conducted at the Department of Microbiology, All India Institute of Medical Sciences, New Delhi. From March 2015 to April 2018 total 400 Cerebro spinal fluid samples were collected aseptically. Samples were processed for cell count, Gram staining, and culture. Culture plates were incubated at 37°C for 18-24 hours. Organism grown on blood and MacConkey agar were identified by MALDI-TOF Vitek MS (BioMerieux, France) and antibiotic susceptibility tests were performed by Kirby Bauer disc diffusion method as per CLSI 2015 guideline. Results: Of the 400 CSF samples processed, 43 (10.75%) were culture positive for different bacteria. Out of 43 isolates, the most prevalent Gram-positive organisms were S. aureus 4 (9.30%) followed by E. faecium 3 (6.97%) & CONS 2 (4.65%). Similarly, E. coli 13 (30.23%) was the commonest Gram-negative isolates followed by A. baumannii 12 (27.90%), K. pneumonia 5 (11.62%) and P. aeruginosa 4(9.30%). Most of the antibiotics tested against the Gram-negative isolates were resistance to them. Colistin was most effective followed by Meropenem and Imepenim for all Gram-negative HAABM isolates. Similarly, most of antibiotics tested were susceptible to S. aureus and CONS. However, E. faecium (100%) were only susceptible to vancomycin and teicoplanin. Conclusion: Hospital acquired acute bacterial meningitis (HAABM) is becoming the emerging challenge as most of isolates are showing resistance to commonly used antibiotics. Gram-negative organisms are emerging as the major player of HAABM. Great care needs to be taken especially in tertiary care hospitals. Similarly, antibiotic stewardship should be followed and antibiotic susceptibility test (AST) should be performed regularly to update the antibiotic patter and to prevent from the emergence of resistance. Updated information of the AST will be helpful for the better management of the meningitis patient.

Keywords: CSF, MALDI-TOF, hospital acquired acute bacterial meningitis, AST

Procedia PDF Downloads 144

Authors: Ammar Asma, Bouafia Nabiha, Ghammam Rim, Ezzi Olfa, Ben Cheikh Asma, Mahjoub Mohamed, Helali Radhia, Sma Nesrine, Chouchène Imed, Boussarsar Hamadi, Njah Mansour

Abstract:

Background: Central venous catheter associated infections (CVC-AI) are among the serious hospital-acquired infections. The aims of this study are to determine the incidence of CVC-AI, and their risk factors among patients followed in a Tunisian medical intensive care unit (ICU). Materials / Methods: A prospective cohort study conducted between September 15th, 2015 and November 15th, 2016 in an 8-bed medical ICU including all patients admitted for more than 48h. CVC-AI were defined according to CDC of ATLANTA criteria. The enrollment was based on clinical and laboratory diagnosis of CVC-AI. For all subjects, age, sex, underlying diseases, SAPS II score, ICU length of stay, exposure to CVC (number of CVC placed, site of insertion and duration catheterization) were recorded. Risk factors were analyzed by conditional stepwise logistic regression. The p-value of < 0.05 was considered significant. Results: Among 192 eligible patients, 144 patients (75%) had a central venous catheter. Twenty-eight patients (19.4%) had developed CVC-AI with density rate incidence 20.02/1000 CVC-days. Among these infections, 60.7% (n=17) were systemic CVC-AI (with negative blood culture), and 35.7% (n=10) were bloodstream CVC-AI. The mean SAPS II of patients with CVC-AI was 32.76 14.48; their mean Charlson index was 1.77 1.55, their mean duration of catheterization was 15.46 10.81 days and the mean duration of one central line was 5.8+/-3.72 days. Gram-negative bacteria was determined in 53.5 % of CVC-AI (n= 15) dominated by multi-drug resistant Acinetobacter baumani (n=7). Staphylococci were isolated in 3 CVC-AI. Fourteen (50%) patients with CVC-AI died. Univariate analysis identified men (p=0.034), the referral from another hospital department (p=0.03), tobacco (p=0.006), duration of sedation (p=0.003) and the duration of catheterization (p=0), as possible risk factors of CVC-AI. Multivariate analysis showed that independent factors of CVC-AI were, male sex; OR= 5.73, IC 95% [2; 16.46], p=0.001, Ramsay score; OR= 1.57, IC 95% [1.036; 2.38], p=0.033, and duration of catheterization; OR=1.093, IC 95% [1.035; 1.15], p=0.001. Conclusion: In a monocenter cohort, CVC-AI had a high density and is associated with poor outcome. Identifying the risk factors is necessary to find solutions for this major health problem.

Keywords: central venous catheter associated infection, intensive care unit, prospective cohort studies, risk factors

Procedia PDF Downloads 347

Authors: Simone F. Medeiros, Jessica M. Fonseca, Gizelda M. Alves, Danilo M. Santos, Sérgio P. Campana-Filho, Amilton M. Santos

Abstract:

Stimuli responsive and biocompatible hydrogel nanoparticles have gained special attention as systems for potential applications in controlled release of drugs to improve their therapeutic efficacy while minimizing side effects. In this work, novel solid dispersions based on thermo- and pH-responsive poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate) hydrogel nanoparticles embedded in chitosan matrices were prepared via spray drying for controlled release of ketoprofen. Firstly, the hydrogel nanoparticles containing ketoprofen were prepared via precipitation polymerization and their stimuli-responsive behavior, thermal properties, chemical composition, encapsulation efficiency and morphology were characterized. Then, hydrogel nanoparticles with different particles size were embedded into chitosan matrices via spray-drying. Scanning electron microscopy (SEM) analyses were performed to investigate the particles size, dispersity and morphology. Finally, ketoprofen release profiles were studied as a function of pH and temperature. Chitosan/poly(NVCL-co-IA-co-EGDMA)-ketoprofen microparticles presented spherical shape, rough surface and pronounced agglomeration, indicating that hydrogels nanoparticles loaded with ketoprofen modified the surface of chitosan matrix. The maximum encapsulation efficiency of ketoprofen into hydrogel nanoparticles was 57.8% and the electrostatic interactions between amino groups from chitosan and carboxylic groups from hydrogel nanoparticles were able to control ketoprofen release. The hydrogel nanoparticles themselves were capable to retard the release of ketoprofen-loaded until 48h of in vitro release tests, while their incorporation into chitosan matrix achieved a maximum percentage of drug release of 45%, using a mass ratio of chitosan: poly(NVCL-co-IA-co-EGDMA equal to 10:7, and 69%, using a mass ratio of chitosan: poly(NVCL-co-IA-co-EGDMA equal to 5:2.

Keywords: hydrogel nanoparticles, poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate), chitosan, ketoprofen, spray-drying

Procedia PDF Downloads 243

Authors: R. A. Abdel Rahman, A. E. Abdel Wahab, E. A. Goghneimy, H. F. Mohamed, E. M. Salama

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Infectious diseases are a major cause of death worldwide. The treatment of infections continues to be problematic in modern time because of the severe side effects of some drugs and the growing resistance to antimicrobial agents. Hence, the search for newer, safer and more potent antimicrobials is a pressing need. Herbal medicines have received much attention as a source of new antibacterial drugs since they are considered time-tested and comparatively safe both for human use and the environment. In the present study, the antimicrobial activity of marjoram (Origanum majorana L.) essential oil on some gram positive and gram negative reference bacteria, as well as some hospital resistant microbes, was tested. Marjoram oil was extracted and the oil chemical constituents were identified using GC/MS analysis. Staphylococcus aureas ATCC 6923, Pseudomonus auregonosa ATCC 9027, Bacillus subtilis ATCC 6633, E. coli ATCC 8736 and two hospital resistant microbes isolates 16 and 21 were used. The two isolates were identified by biochemical tests and 16s rRNA as proteus spp. and Enterococcus facielus. The effect of different concentrations of essential oils on bacterial growth was tested using agar disk diffusion assay method to determine the minimum inhibitory concentrations and using micro dilution method to determine the minimum bactericidal concentrations. Marjoram oil was found to be effective against both reference and hospital resistance strains. Hospital strains were more resistant to marjoram oil than reference strains. P. auregonosa growth was completely inhibited at a low concentration of oil (4µl/ml). The other reference strains showed sensitivity to marjoram oil at concentrations ranged from 5 to 7µl/ml. The two hospital strains showed sensitivity at media containing 10 and 15µl/ml oil. The major components of oil were terpineol, cis-beta (23.5%), 1,6 – octadien –3-ol,3,7-dimethyl, 2 aminobenzoate (10.9%), alpha terpieol (8.6%) and linalool (6.3%). Scanning electron microscope (SEM) and transmission electron microscope (TEM) analysis were used to determine the difference between treated and untreated hospital strains. SEM results showed that treated cells were smaller in size than control cells. TEM data showed that cell lysis has occurred to treated cells. Treated cells have ruptured cell wall and appeared empty of cytoplasm compared to control cells which shown to be intact with normal volume of cytoplasm. The results indicated that marjoram oil has a positive antimicrobial effect on hospital resistance microbes. Natural crude extracts can be perfect resources for new antimicrobial drugs.

Keywords: antimicrobial activity, essential oil, hospital resistance microbes, marjoram

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Authors: Adepeju Simon-Oke, Olatunji Odeyemi, Mobolanle Oniya

Abstract:

Urinary tract infection has become the most common bacterial infections in humans, both at the community and hospital settings; it has been reported in all age groups and in both sexes. This study was carried out in order to determine and evaluate the prevalence, current drug susceptibility pattern of the isolated organisms and identify the associated risk factors of UTIs among the pregnant women in Akure, Ondo State, Nigeria. A cross-sectional study was conducted on the urine of pregnant women, and socio-demographic information of the women was collected. A total of 300 clean midstream urine samples were collected, and a general urine microscopic examination and culture were carried out, the Microbact identification system was used to identify gram-negative bacteria. Out of the 300 urine samples cultured, 183(61.0%) yielded significant growth of urinary pathogens while 117(39.0%) yielded either insignificant growth or no growth of any urinary pathogen. Prevalence of UTI was significantly associated with the type of toilet used, symptoms of UTI, and previous history of urinary tract infection (p<0.05). Escherichia coli 58(31.7%) was the dominant pathogen isolated, and the least isolated uropathogens were Citrobacter freudii and Providencia retgerri 2(1.1%) respectively. Gram-negative bacteria showed 77.6%, 67.9%, and 61.2% susceptibility to ciprofloxacin, augmentin, and chloramphenicol, respectively. Resistance against septrin, chloramphenicol, sparfloxacin, amoxicillin, augmentin, gentamycin, pefloxacin, trivid, and streptomycin was observed in the range of 23.1 to 70.1%. Gram-positive uropathogens isolated showed high resistance to amoxicillin (68.4%) and high susceptibility to the remaining nine antibiotics in the range 65.8% to 89.5%. This study justifies that pregnant women are at high risk of UTI. Therefore screening of pregnant women during antenatal clinics should be considered very important to avoid complications. Health education with regular antenatal and personal hygiene is recommended as precautionary measures to UTI.

Keywords: pregnant women, prevalence, risk factor, UTIs

Procedia PDF Downloads 122

Authors: Djebbar Atmani, Aghiles Karim Aissat, Nadjet Debbache-Benaida, Nassima Chaher-Bazizi, Dina Atmani-Kilani, Meriem Rahmani-Berboucha, Naima Saidene, Malika Benloukil, Lila Azib

Abstract:

Medicinal plants are believed to be an important source for the discovery of potential antioxidant, anti-inflammatory and anti-diabetic substances. The present study was designed to investigate the neuroprotective, anti-inflammatory, anti-diabetic and anti-hyperuricemic potential of Pistacia lentiscus, as well as the identification of active compounds. The antioxidant potential of plant extracts against known radicals was measured using various standard in vitro methods. Anti-inflammatory activity was determined using the paw edema model in mice and by measuring the secretion of the pro-inflammatory cytokine, whereas the anti-diabetic effect was assessed in vivo on streptozotocin-induced diabetic rats and in vitro by inhibition of alpha-amylase. The anti-hyperuricemic activity was evaluated using the xanthine oxidase assay, whereas neuroprotective activity was investigated using an Aluminum-induced toxicity test. Pistacia lentiscus extracts and fractions exhibited high scavenging capacity against DPPH, NO. and ABTS+ radicals in a dose-dependent manner and restored blood glucose levels, in vivo, to normal values, in agreement with the in vitro anti-diabetic effect. Oral administration of plant extracts significantly decreased carrageenan-induced mice paw oedema, similar to the standard drug, diclofenac, was effective in reducing IL-1β levels in cell culture and induced a significant increase in urinary volume in mice, associated to a promising anti-hyperuricemic activity. Plant extracts showed good neuroprotection and restoration of cognitive functions in mice. HPLC-MS and NMR analyses allowed the identification of known and new phenolic compounds that could be responsible for the observed activities. Therefore, Pistacia lentiscus could be beneficial in the treatment of inflammatory conditions and diabetes complications and the enhancement of cognitive functions.

Keywords: Pistacia lentiscus, anti-inflammatory, antidiabetic, flavanols, neuroprotective

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Authors: S. Sreeja, Radhakrishnan R. Nair, Noble Gracious, Sreeja S. Nair, M. Radhakrishna Pillai

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Background: Tacrolimus is a potent immunosuppressant clinically used for the long term treatment of antirejection of transplanted organs in liver and kidney transplant recipients though dose optimization is poorly managed. However, So far no study has been carried out on the South Indian kidney transplant patients. The objective of this study is to evaluate the potential influence of a functional polymorphism in CYP3A5*3 gene on tacrolimus physiological availability/dose ratio in South Indian renal transplant patients. Materials and Methods: Twenty five renal transplant recipients receiving tacrolimus were enrolled in this study. Their body weight, drug dosage, and therapeutic concentration of Tacrolimus were observed. All patients were on standard immunosuppressive regime of Tacrolimus-Mycophenolate mofetil along with steroids on a starting dose of Tac 0.1 mg/kg/day. CYP3A5 genotyping was performed by PCR followed with RFLP. Conformation of RFLP analysis and variation in the nucleotide sequence of CYP3A5*3 gene were determined by direct sequencing using a validated automated generic analyzer. Results: A significant association was found between tacrolimus per dose/kg/d and CYP3A5 gene (A6986G) polymorphism in the study population. The CYP3A5 *1/*1, *1/*3 and *3/*3 genotypes were detected in 5 (20 %), 5 (20 %) and 15 (60 %) of the 25 graft recipients, respectively. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus Concentration/Dose ratio in kidney transplant recipients. Significantly higher L/D was observed among non-expressors 9.483 ng/mL(4.5- 14.1) as compared with the expressors 5.154 ng/mL (4.42-6.5 ) of CYP3A5. Acute rejection episodes were significantly higher for CYP3A5*1 homozygotes compared to patients with CYP3A5*1/*3 and CYP3A5*3/*3 genotypes (40 % versus 20 % and 13 %, respectively ). The dose normalized TAC concentration (ng/ml/mg/kg) was significantly lower in patients having CYP3A5*1/*3 polymorphism. Conclusion: This is the first study to extensively determine the effect of CYP3A5*3 genetic polymorphism on tacrolimus pharmacokinetics in South Indian renal transplant recipients and also shows that majority of our patients carry mutant allele A6986G in CYP3A5*3 gene. Identification of CYP3A5 polymorphism prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus for each patient.

Keywords: kidney transplant patients, CYP3A5 genotype, tacrolimus, RFLP

Procedia PDF Downloads 282

Authors: Ahilya Singh, Brad Carte, Ramesh Subramani, William Aalbersberg

Abstract:

A total of 37 actinomycete strains were purified from 25 Solomon Islands marine sediments using four different types of isolation media. Among them, 54% of the strains had obligate requirement of seawater for growth. The ethyl acetate extract of 100 ml fermentation product of each strain was screened for antimicrobial activity against multidrug resistant human pathogens and cytotoxic activity against brine shrimps. A total of 67% of the ethyl acetate extracts showed antimicrobial and/or cytotoxic activities. A strain F-1915 was selected for isolation and evaluation of bioactive compound(s) based on its bioactive properties and chemical profile analysis using the LC-MS. The strain F-1915 was identified to have 96% sequence similarity to Streptomyces violaceusniger on the basis of 16S rDNA sequences using BLAST analysis. The 16S rDNA revealed that the strain F-1915 is a new member of MAR4 clade of actinomycetes. The MAR4 clade is an interesting clade of actinomycetes known for the production of pharmaceutically important hybrid isoprenoid compounds. The ethyl acetate extract of the fermentation product of this strain was purified by silica gel column chromatography and afforded the isolation of one bioactive pure compound. Based on the 1D and 2D NMR spectral data of compound 1 it was identified as a new mono-brominated phenazinone, Marinophenazimycin A, a structure which has already been studied by external collaborators at Scripps Institution of Oceanography but is yet to be published. Compound 1 displayed significant antimicrobial activity against drug resistant human pathogens. The minimum inhibitory concentration (MIC) of compound 1 was against Methicillin Resistant Staphylococcus aureus (MRSA) was about 1.9 μg/ml and MIC recorded against Amphotericin Resistant Candida albicans (ARCA) was about 0.24 μg/ml. The bioactivity of compound 1 against ARCA was found to be better than the standard antifungal agent amphotericin B. Compound 1 however did not show any cytotoxic activity against brine shrimps.

Keywords: actinomycetes, antimicrobial activity, brominated phenazine, MAR4 clade, marine natural products, multidrug resistent, 1D and 2D NMR

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