Search results for: anti-viral drug

Authors: Saha Saradindu, Das Payel, Somdeb BoseDasgupta

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Tuberculosis caused by Mycobacteria tuberculosis is a dreadful disease and more so with the advent of extreme and total drug-resistant species. Mycobacterial pathogenesis is an ever-changing paradigm from phagosome maturation block to phagosomal escape into macrophage cytosol and finally acid tolerance and survival inside the lysosome. Mycobacteria are adept at subverting the host immune response by highjacking host cell signaling and secreting virulence factors. One such virulence factor is a ser/thr kinase; Protein kinase G (PknG), which is known to prevent phagosome maturation. The host substrates of PknG, allowing successful pathogenesis still remain an enigma. Hence we carried out a comparative phosphoproteomic screen and identified a number of substrates phosphorylated by PknG. We characterized some of these substrates in vivo and in vitro and observed that PknG mediated phosphorylation of these substrates leads to reduced TNFa production as well as decreased response to TNFa induced macrophage necroptosis, thus enabling mycobacterial survival and proliferation.

Keywords: mycobacteria, Protein kinase G, phosphoproteomics, necroptosis

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Authors: Faisal A. Salih, V. V. Egorov

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Verapamil is a drug used in medicine for arrhythmia, angina, and hypertension as a calcium channel blocker. In this study, a Verapamil-selective electrode was prepared, and the concentrations of the components in the membrane were as follows: PVC (32.8 wt %), O-NPhOE (66.6 wt %), and KTPClPB (0.6 wt % or approximately 0.01 M). The inner solution containing verapamil hydrochloride 1 x 10⁻³ M was introduced, and the electrodes were conditioned overnight in 1 x 10⁻³ M verapamil hydrochloride solution in 1 x 10⁻³ M orthophosphoric acid. These studies have demonstrated that O-NPhOE and KTPClPB are the best plasticizers and ion exchangers, while both direct potentiometry and potentiometric titration methods can be used for the determination of verapamil hydrochloride in tablets and injection solutions. Normalized weights of verapamil per tablet (80.4±0.2, 80.7±0.2, 81.0±0.4 mg) were determined by direct potentiometry and potentiometric titration, respectively. Weights of verapamil per average tablet weight determined by the methods of direct potentiometry and potentiometric titration were" 80.4±0.2, 80.7±0.2 mg determined for the same set of tablets, respectively. The masses of verapamil in solutions for injection, determined by direct potentiometry for two ampoules from one set, were (5.00±0.015, 5.004±0.006) mg. In all cases, good reproducibility and excellent correspondence with the declared quantities were observed.

Keywords: verapamil, potentiometry, ion-selective electrode, lipophilic physiologically active amines

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Authors: Alisha Gupta

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Osteoarthritis (OA) is the most common form of arthritis which is a degenerative joint disease causing joints to begin to break down and underlying bones to change. This “wear and tear” most frequently affects hands, hips, and knees. This is important because OA pain is considered to be a leading cause of mobility impairment in older adults, with hip and knee OA ranked 11th highest contributors to global disability. Bone tissue engineering utilizing polymer scaffolds and hydrogels is an emerging field for treating osteoarthritis. Polymer scaffolds provide a three-dimensional structure for tissue growth, and hydrogels can be used to deliver drugs and growth factors. The combination of the two materials creates a hybrid structure that can better withstand physiological and mechanical demands while also providing a more controlled environment for drug and nutrient delivery. I think using bone tissue engineering for making scaffold-hydrogel composites that are self-regenerating and vascularizing might be useful in solving this problem. Successful implementation can reconstruct healthy, simulated bone tissue on deficient applicants.

Keywords: tissue engineering, regenerative medicine, scaffold-hydrogel composites, osteoarthritis

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Authors: Christina Drosou, Konstantina E. Kyriakopoulou, Andreas Bimpilas, Dimitrios Tsimogiannis, Magdalini C. Krokida

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Rationale: Agiorgitiko is one of the most widely-grown and commercially well-established red wine varieties in Greece. Each year viticulture industry produces a large amount of waste consisting of grape skins and seeds (pomace) during a short period. Grapes contain polyphenolic compounds which are partially transferred to wine during winemaking. Therefore, winery wastes could be an alternative cheap source for obtaining such compounds with important antioxidant activity. Specifically, red grape waste contains anthocyanins and flavonols which are characterized by multiple biological activities, including cardioprotective, anti-inflammatory, anti-carcinogenic, antiviral and antibacterial properties attributed mainly to their antioxidant activity. Ultrasound assisted extraction (UAE) is considered an effective way to recover phenolic compounds, since it combines the advantage of mechanical effect with low temperature. Moreover, green solvents can be used in order to recover extracts intended for used in the food and nutraceutical industry. Apart from the extraction, pre-treatment process like drying can play an important role on the preservation of the grape pomace and the enhancement of its antioxidant capacity. Objective: The aim of this study is to recover natural extracts from winery waste with high antioxidant capacity using green solvents so they can be exploited and utilized as enhancers in food or nutraceuticals. Methods: Agiorgitiko grape pomace was dehydrated by air drying (AD) and accelerated solar drying (ASD) in order to explore the effect of the pre-treatment on the recovery of bioactive compounds. UAE was applied in untreated and dried samples using water and water: ethanol (1:1) as solvents. The total antioxidant potential and phenolic content of the extracts was determined using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay and Folin-Ciocalteu method, respectively. Finally, the profile of anthocyanins and flavonols was specified using HPLC-DAD analysis. The efficiency of processes was determined in terms of extraction yield, antioxidant activity, phenolic content and the anthocyanins and flavovols profile. Results & Discussion: The experiments indicated that the pre-treatment was essential for the recovery of highly nutritious compounds from the pomace as long as the extracts samples showed higher phenolic content and antioxidant capacity. Water: ethanol (1:1) was considered a more effective solvent on the recovery of phenolic compounds. Moreover, ASD grape pomace extracted with the solvent system exhibited the highest antioxidant activity (IC50=0.36±0.01mg/mL) and phenolic content (TPC=172.68±0.01mgGAE/g dry extract), followed by AD and untreated pomace. The major compounds recovered were malvidin3-O-glucoside and quercetin3-O-glucoside according to the HPLC analysis. Conclusions: Winery waste can be exploited for the recovery of nutritious compounds using green solvents such as water or ethanol. The pretreatment of the pomace can significantly affect the concentration of phenolic compounds, while UAE is considered a highly effective extraction process.

Keywords: agiorgitico grape pomace, antioxidants, phenolic compounds, ultrasound assisted extraction

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Authors: Mary Ghobrial, Sahar Wefky

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Marine macroalgae have proven to be rich source of bioactive compounds with biomedical potential, not only for human but also for veterinary medicine. Emergence of microbial disease in aquaculture industries implies serious loses. Usage of commercial antibiotics for fish disease treatment produces undesirable side effects. Marine organisms are a rich source of structurally novel biologically active metabolites. Competition for space and nutrients led to the evolution of antimicrobial defense strategies in the aquatic environment. The interest in marine organisms as a potential and promising source of pharmaceutical agents has increased in the last years. Many bioactive and pharmacologically active substances have been isolated from microalgae. Compounds with antibacterial, antifungal and antiviral activities have been also detected in green, brown and red algae. Selected species of marine benthic algae belonging to the Phaeophyta and Rhodophyta, collected from different coastal areas of Alexandria (Egypt), were investigated for their antibacterial and antifungal, activities. Macroalgae samples were collected during low tide from the Alexandria Mediterranean coast. Samples were air dried under shade at room temperature. The dry algae were ground, using electric mixer grinder. They were soaked in 10 ml of each of the solvents acetone, ethanol, methanol and hexane. Antimicrobial activity was evaluated using well-cut diffusion technique In vitro screening of organic solvent extracts from the marine macroalgae Laurencia pinnatifida, Pterocladia capillaceae, Stepopodium zonale, Halopteris scoparia and Sargassum hystrix, showed specific activity in inhibiting the growth of five virulent strains of bacteria pathogenic to fish Pseudomonas fluorescens, Aeromonas hydrophila, Vibrio anguillarum, V. tandara, Escherichia coli and two fungi Aspergillus flavus and A. niger. Results showed that, acetone and ethanol extracts of all test macroalgae exhibited antibacterial activity, while acetone extract of the brown Sargassum hystrix displayed the highest antifungal activity. The extracts of seaweeds inhibited bacteria more strongly than fungi and species of the Rhodophyta showed the greatest activity against the bacteria rather than fungi tested. The gas liquid chromatography coupled with mass spectrometry detection technique allows good qualitative and quantitative analysis of the fractionated extracts with high sensitivity to the smaller amounts of components. Results indicated that, the main common component in the acetone extracts of L. pinnatifida and P. capillacea is 4-hydroxy-4-methyl2-pentanone representing 64.38 and 58.60%. Thus, the extracts derived from the red macroalgae were more efficient than those obtained from the brown macroalgae in combating bacterial pathogens rather than pathogenic fungi. The most preferred species over all was the red Laurencia pinnatifida. In conclusion, the present study provides the potential of red and brown macroalgae extracts for development of anti-pathogenic agents for use in fish aquaculture.

Keywords: bacteria, fungi, extracts, solvents

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Authors: Wei-Ting Kuo, Feng-Huei Lin

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Epidermal growth factor receptor (EGFR) is often constitutively stimulated in cancer owing to the binding of ligands such as epidermal growth factor (EGF), so it is necessary to investigate the interaction between EGFR and its targeting biomolecules which were over ligands binding. This study would focus on the binding affinity and adhesion force of two targeting products anti-EGFR monoclonal antibody (mAb) and peptide A to EGFR comparing with EGF. Surface plasmon resonance (SPR) was used to obtain the equilibrium dissociation constant to evaluate the binding affinity. Atomic force microscopy (AFM) was performed to detect adhesion force. The result showed that binding affinity of mAb to EGFR was higher than that of EGF to EGFR, and peptide A to EGFR was lowest. The adhesion force between EGFR and mAb that was higher than EGF and peptide A to EGFR was lowest. From the studies, we could conclude that mAb had better adhesion force and binding affinity to EGFR than that of EGF and peptide A. SPR and AFM could confirm the interaction between receptor and targeting ligand easily and carefully. It provide a platform to screen ligands for receptor targeting and drug delivery.

Keywords: adhesion force, binding affinity, epidermal growth factor receptor, target molecule

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Authors: Essia Sebai, Amel Abidi, Hayet benyeddem, Akkari Hafidh

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Herbal extracts are of particular interest to the drug industry; essential oil with significant anthelmintic activity has the potential to be used as an alternative to conventional chemical drugs. In the present study, we describe the chemical profile of Laurus nobilis essential oil (EO), the in vitro anthelmintic activity of laurel oil against Haemonchus contortus and its in vivo anthelmintic effect against the murine helminth parasite model Heligmosomoides polygyrus. The chromatographic profile of L. nobilis (EO) extracted from the leaves of L. nobilis has shown the presence of monoterpenes 1,8-cineol (Eucalyptol) (29.47%), D-Limonène (18.51%) and Linalool (10.84%) in high fractions. The in vitro anthelmintic potential was expressed by an ovicidal effect against H. contortus egg hatching with an inhibition value of 3.23 mg/mL and 87.5% of immobility of adult worms after 8 hours of exposure to 8 mg/mL of L. nobilis EO. Regarding the in vivo anthelmintic potential, L. nobilis (EO) at 2400 mg/kg completely eliminated the egg output of H. polygyrus after seven days of oral treatment, together with a 79.2% of reduction in total worm counts. Based on the obtained funding, L. nobilis EO showed promising in vitro and in vivo anthelmintic capacities against gastrointestinal parasites.

Keywords: lauris nobilis, anthelmintic, haemonchus, pylogyrus

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Authors: Suzanne Overstreet-Juenke

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Disproportionate minority contact (DMC) is a salient issue that has been found at every stage of the decision-making process in the juvenile justice system. Existing research indicates that DMC influences adjudication for drug, property, and personal crimes. Because intimate partner violence (IPV) is a major public health problem and global concern, the current study examines DMC at adjudication among youth charged for crimes of interpersonal violence. This research uses administrative, Court Designated Worker (CDW) data collected from 2014 to 2016. The results are contextualized using Steffensmeier’s version of focal concerns theory of judicial decision-making. This study assesses race and two seriousness of offense measures to establish whether a link exists between race and adjudication. The results of the study is similar to prior research on the topic. These results are discussed in terms of policy implications, limitations, and future research.

Keywords: race, disproportionate minority contact, focal concerns theory, juvenile

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Authors: S. K. Hemalata, M. N. Shiva Kameshwari

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The present work focusses on anti-inflammatory action of Urginea wightii in-vitro. Urginea wightii is a member of Hyacinthaceae and considered to be wonder plant because of its varied important medicinal properties. The plant is endemic to India, Africa, and Mediterranian regions. Presence of alkaloids, flavonoid-glycosides especially flavonone derivatives are responsible for the strong anti-inflammatory activity of Urginea wightii. In present research work, anti-inflammatory activity of methanol extract of the bulb powder was tested on Male Wistar Rats. In these test animals, inflammation was induced by injecting carrageenan as the irritant to induce paw edema in Wistar rats. Inflammation of Paw edema was treated with both plant extract and Pyrox gel a known synthetic anti-inflammatory drug through external application. The result indicated that anti-inflammatory activity of Urginea wightii extract was almost similar to the synthetic Pyrox gel. This disproves the modern world's scepticism towards the herbal medicines and encourages to rely on natural plant extracts.

Keywords: anti-inflammatory activity, flavonoid-glycosides, Pyrox gel, Urginia wightii

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Authors: D. Benmoussa, H. Hannache, O. Cherkaoui

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In textiles, the major interest in microencapsulation is currently in the application of durable fragrances, skin softeners, phase-change materials, antimicrobial agents and drug delivery systems onto textile materials. In our research “Polyethylene Glycol” was applied as phase change material and it was encapsulated in polymethacrylic acid (PMA) by radical polymerization in suspension of methacrylic acid in presence of N,N'-methylenebisacrylamide (MBAM) as crosslinking agent. Thereafter the obtained microcapsule was modified by amidation with ethylenediamine as a spacer molecule. At the end of this spacer trichlorotriazine reactive group was fixed. Microcapsules were grafted onto cotton textile substrate. The surface morphologies of the microencapsulated phase change materials (micro PCMs) were studied by scanning electron microscopy (SEM). Thermal properties, thermal reliabilities and thermal stabilities of the as-prepared micro PCMs were investigated by differential scanning calorimetry (DSC) and thermogravmetric analysis (TGA). The results obtained show the obtaining microcapsules with a mean diameter of 10 µm and the resistance of the microcapsules is demonstrated by thermal analysis.

Keywords: energy storage, microencapsulation, phase-change materials, thermogravmetric analysis (TGA)

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Authors: Michaela Chovancova, Pavel Niedoba

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For the treatment of acute and chronic lung diseases it is preferred to deliver medicaments by inhalation. The drug is delivered directly to tracheobronchial tree. This way allows the given medicament to get directly into the place of action and it makes rapid onset of action and maximum efficiency. The transport of aerosol particles in the particular part of the lung is influenced by their size, anatomy of the lungs, breathing pattern and airway resistance. This article deals with calculation of airway resistance in the lung model of Horsfield. It solves the problem of determination of the pressure losses in bifurcation and thus defines the pressure drop at a given location in the bronchial tree. The obtained data will be used as boundary conditions for transport of aerosol particles in a central part of bronchial tree realized by Computational Fluid Dynamics (CFD) approach. The results obtained from CFD simulation will allow us to provide information on the required particle size and optimal inhalation technique for particle transport into particular part of the lung.

Keywords: human lungs, bronchial tree, pressure losses, airways resistance, flow, breathing

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Authors: Rahul Agarwal, Ashutosh Singh

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Colorectal cancer (CRC) also refers as bowel cancer or colon cancer. It involves the development of abnormal growth of cells in colon or rectum part of the body. This work leads to the development of a miRNA database in colorectal cancer. We named this database- miCoRe. This database comprises of all validated colon-rectal cancer miRNAs information from various published literature with an effectual knowledge based information retrieval system. miRNAs have been collected from various published literature reports. MySQL is used for main-framework of miCoRe while the front-end was developed in PHP script. The aim of developing miCoRe is to create a comprehensive central repository of colorectal carcinoma miRNAs with all germane information of miRNAs and their target genes. The current version of miCoRe consists of 238 miRNAs which are known to be implicated in malignancy of CRC. Alongside with miRNA information, miCoRe also contains the information related to the target genes of these miRNA. miCoRe furnishes the information about the mechanism of incidence and progression of the disease, which would further help the researchers to look for colorectal specific miRNAs therapies and CRC specific targeted drug designing. Moreover, it will also help in development of biomarkers for the better and early detection of CRC and will help in better clinical management of the disease.

Keywords: colorectal cancer, database, miCoRe, miRNAs

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Authors: J. Ticona Chambi, E. A. De Almeida, C. A. Andrade Raymundo Gaiotto, A. M. Do Espírito Santo, L. Infantes, S. L. Cuffini

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The solubility of active pharmaceutical ingredients (APIs) is challenging for the pharmaceutical industry. The new multicomponent crystalline forms as cocrystal and solvates present an opportunity to improve the solubility of APIs. Commonly, the procedure to obtain multicomponent crystalline forms of a drug starts by screening the drug molecule with the different coformers/solvents. However, it is necessary to develop methods to obtain multicomponent forms in an efficient way and with the least possible environmental impact. The Hansen Solubility Parameters (HSPs) is considered a tool to obtain theoretical knowledge of the solubility of the target compound in the chosen solvent. H-Bond Propensity (HBP), Molecular Complementarity (MC), Coordination Values (CV) are tools used for statistical prediction of cocrystals developed by the Cambridge Crystallographic Data Center (CCDC). The HSPs and the CCDC tools are based on inter- and intra-molecular interactions. The curcumin (Cur), target molecule, is commonly used as an anti‐inflammatory. The demethoxycurcumin (Demcur) and bisdemethoxycurcumin (Bisdcur) are natural analogues of Cur from turmeric. Those target molecules have differences in their solubilities. In this way, the work aimed to analyze and compare different tools for multicomponent forms prediction (solvates) of Cur, Demcur and Biscur. The HSP values were calculated for Cur, Demcur, and Biscur using the chemical group contribution methods and the statistical optimization from experimental data. The HSPmol software was used. From the HSPs of the target molecules and fifty solvents (listed in the HSP books), the relative energy difference (RED) was determined. The probability of the target molecules would be interacting with the solvent molecule was determined using the CCDC tools. A dataset of fifty molecules of different organic solvents was ranked for each prediction method and by a consensus ranking of different combinations: HSP, CV, HBP and MC values. Based on the prediction, 15 solvents were selected as Dimethyl Sulfoxide (DMSO), Tetrahydrofuran (THF), Acetonitrile (ACN), 1,4-Dioxane (DOX) and others. In a starting analysis, the slow evaporation technique from 50°C at room temperature and 4°C was used to obtain solvates. The single crystals were collected by using a Bruker D8 Venture diffractometer, detector Photon100. The data processing and crystal structure determination were performed using APEX3 and Olex2-1.5 software. According to the results, the HSPs (theoretical and optimized) and the Hansen solubility sphere for Cur, Demcur and Biscur were obtained. With respect to prediction analyses, a way to evaluate the predicting method was through the ranking and the consensus ranking position of solvates already reported in the literature. It was observed that the combination of HSP-CV obtained the best results when compared to the other methods. Furthermore, as a result of solvent selected, six new solvates, Cur-DOX, Cur-DMSO, Bicur-DOX, Bircur-THF, Demcur-DOX, Demcur-ACN and a new Biscur hydrate, were obtained. Crystal structures were determined for Cur-DOX, Biscur-DOX, Demcur-DOX and Bicur-Water. Moreover, the unit-cell parameter information for Cur-DMSO, Biscur-THF and Demcur-ACN were obtained. The preliminary results showed that the prediction method is showing a promising strategy to evaluate the possibility of forming multicomponent. It is currently working on obtaining multicomponent single crystals.

Keywords: curcumin, HSPs, prediction, solvates, solubility

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Authors: Nantawan Soonklang, Linda Chularojanamontri, Urarat Nanna

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Ethnopharmacological relevance: Thunbergia laurifolia Lindl. belongs to the family Acanthaceae commonly known as Rang jeud in Thailand. This plant is traditionally used in Thailand for centuries as an antidote for several poisons and drug overdose. Aim of the study: This research aimed to study the analgesic and antipyretic activities of T. laurifolia water extract by using animal models. Materials and Methods: The analgesic activity was studied using 2 methods of pain induction including acetic acid and heat induced pain. And the antipyretic activity study was performed by yeast-induced hyperthermia. Results: The results showed that the administration of T. laurifolia extract possessed analgesic activity by reducing acetic acid-induced writhing response and heat-induced pain as well as showed antipyretic activity by decreasing body temperature of hyperthermic rats induced by brewer’s yeast. Conclusion: The study indicates that the T. laurifolia extract possesses analgesic and antipyretic activities in animals.

Keywords: Thunbergia laurifolia extract, analgesic activity, antipyretic activity, hyperthermia

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Authors: Sangbok Lee

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There has been much effort on process improvement for outpatient clinics to provide quality and acute care to patients. One of the efforts is no-show analysis or prediction. This work analyzes patient no-shows along with patient health conditions. The health conditions refer to clinical symptoms that each patient has, out of the followings; hyperlipidemia, diabetes, metastatic solid tumor, dementia, chronic obstructive pulmonary disease, hypertension, coronary artery disease, myocardial infraction, congestive heart failure, atrial fibrillation, stroke, drug dependence abuse, schizophrenia, major depression, and pain. A dataset from a regional hospital is used to find the relationship between the number of the symptoms and no-show probabilities. Additional analysis reveals how each symptom or combination of symptoms affects no-shows. In the above analyses, cross-classification of patients by age and gender is carried out. The findings from the analysis will be used to take extra care to patients with particular health conditions. They will be forced to visit clinics by being informed about their health conditions and possible consequences more clearly. Moreover, this work will be used in the preparation of making institutional guidelines for patient reminder systems.

Keywords: healthcare system, no show analysis, process improvment, statistical data analysis

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Authors: Raquel Dafouz Neus Cáceres, Javier Fernandez-Rubio, Belinda Huerta José Luis Rodríguez-Gil, Nicola Mastroianni, Miren López de Alda, Damià Barceló, Yolanda Valcárcel

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The region of Galicia, found in north-western (NW) Spain, is a national and world leader in shellfish, especially mussel production, and recognized for its fishing industry. Few studies have evaluated the presence of emerging contaminants in NW Spain, with those published mainly concerning the continental aquatic environment. The objective of this study was to identify the environmental risk posed by the presence of pharmaceuticals and drugs of abuse in this important coastal region. The presence of sixteen pharmaceuticals (benzodiazepines, anxiolytics, and caffeine), and 19 drugs of abuse (cocainics, amphetamine-like compounds, opiates and opioids, lysergic compounds, and cannabinoids) was assessed in 23 sites located in the Rías (Coastal inlets) of Muros, Arousa, and Pontevedra (NW Spain). Twenty-two of these locations were affected by waste-water treatment plant (WWTP) effluents, and one represented the effluent of one of these WWTPs. Venlafaxine was the pharmaceutical compound detected at higher concentration in the three Rías, with a maximum value of 291 ng/L at the site Porto do Son (Ría de Muros). Total concentration in the three Rías was 819,26 ng/L. Next, citalopram and lorazepam were the most prevalent compounds detected. Metabolite of cocaine benzoylecgonine was the drug of abuse with the highest concentration, measured at 972 ng/L in the Ría of Noia WWTP (no dilution). This compound was also detected at 142 ng/L in the site La Isla de Aros, Ría of Pontevedra. Total concentration for the three Rías was 1210 ng/L. Ephedrine was also detected at high level in the three Rías, with a total concentration of 579,28 ng/L. The results obtained for caffeine show maximum and average concentrations of 857 ng/L Isla de Arosa, Ría de Pontevedra the highest measured in seawater in Spain. A preliminary hazard assessment was carried out by comparing these measured environmental concentrations (MEC) to predicted no-effect concentrations (PNECs) for aquatic organisms. Six out of the 22 seawater samples resulted in a Hazard Quotient (HQ) from chronic exposure higher than 1 with the highest being 17.14, indicating a high probability of adverse effects in the aquatic environment. In addition, the risk was assessed on the basis of persistence, bioaccumulation, and toxicity (PBT). This work was financially supported by the Spanish Ministry of Economy and Competitiveness through the Carlos III Health Institute and the program 'Proyectos de Investigacion en Salud 2015-2017' FIS (PI14/00516), the European Regional Development Fund (ERDF), the Catalan Government (Consolidated Research Groups '2014 SGR 418 - Water and Soil Quality Unit' and 2014 SGR 291 - ICRA), and the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 603437. The poster entitled 'Environmental Risk of Pharmaceuticals, Drugs of Abuse and Stimulant Caffeine in Marine Water: A Case Study in the North-Western of Spain'.

Keywords: drug of abuse, pharmaceuticals, caffeine, environmental risk, seawater

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Authors: Siao-Wei Jiang, Boy-Young Hsieh, Ching-Liang Hsieh, Cheng-Yung Lin

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The problems of multiple drug resistance in the pig farming industry have been emphasized in recent years. Diarrhea syndrome is common in weaning piglets and often treated with antibiotics as a feed additive, leading to the rapid spread of antibiotic resistance and posing high health risks to humans. The study aimed to alleviate diarrhea syndrome with traditional herbal medicine, Xiang Sha Liu Jun Zi Tang, whose effects enhanced digestive function. Piglets at 4 weeks old with stool classified to Bristol stool classification type 6 or type 7 were randomly divided into the control group, group A (1% of Xiang Sha Liu Jun Zi Tang) and group B (0.1% Colistin). The piglets were administrated for 7 days, and their weight, feed intake, and stool score were recorded daily before and after the trial. The results showed that the diarrhea index score in group A and group B improved significantly compared to the control group, indicating that Xiang Sha Liu Jun Zi Tang may have the same effect on alleviating diarrhea syndrome as Colistin, and it may be another replacement for antibiotics.

Keywords: pig, diarrhea, herbal medicine, Xiang Sha Liu Jun Zi Tang

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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Authors: Fernando G. Torres, Omar P. Troncoso

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Starch is a highly biocompatible, non-toxic, and biodegradable polymer. It is widely used in biomedical applications, including drug delivery systems and tissue engineering scaffolds. Curcumin, a phenolic compound found in the dried root of Curcuma longa, has been used as a nutritional supplement due to its antimicrobial, anti-inflammatory, and antioxidant effects. However, the major problem with ingesting curcumin by itself is its poor bioavailability due to its poor absorption and rapid metabolism. In this study, we report a novel methodology to prepare starch nanoparticles loaded with curcumin. The nanoparticles were synthesized via nanoprecipitation of starch granules extracted from native Andean potatoes (Solanum tuberosum ssp. and Andigena var Huamantanga varieties). The nanoparticles were crosslinked and stabilized by using sodium tripolyphosphate and Tween®80, respectively. The characterization of the nanoparticles loaded with curcumin was assessed by Fourier Transform Infrared Spectroscopy, Dynamic Light Scattering, Zeta potential, and Differential scanning calorimetry. UV-vis spectrophotometry was used to evaluate the loading efficiency and capacity of the samples. The results showed that native starch nanoparticles could be used to prepare promising nanocarriers for the controlled release of curcumin.

Keywords: starch nanoparticle, nanoprecipitation, curcumin, biomedical applications

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Authors: Bhargavi Santebennur Dwarakanath, Praveen Vadakke Kamath, Savitha Janakiraman

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Cervical cancer is one of the leading causes of mortality in women and is the second most common malignancy worldwide. Lovastatin, a non polar, anticholesterol drug which also exerts antitumour activity in vitro. In the present study, lovastatin from Aspergillus terreus (KM017963) was purified by adsoprtion chromatography and evaluated for its anticancer and anti-oxidant properties in human cervical cancer cell lines (HeLa). The growth inhibitory and proapoptotic effects of purified lovastatin on HeLa cell lines were investigated by determining its influence on cytotoxicity, Mitochondrial Membrane Potential (MMP), DNA fragmentation and antioxidant property (Hydroxy radical scavenging effect and the levels of total reduced glutathione). Flow cytometry analysis by propidium iodide staining confirmed the induction of apoptotic cell death and revealed cell cycle arrest at G0/G1 phase. Results of the study give leads for anticancer effects of lovastatin and its potential efficacy in the chemotherapy of cervical cancer.

Keywords: apoptosis, Aspergillus terreus, cervical cancer, lovastatin

Procedia PDF Downloads 307

Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri

Abstract:

Dosimetry is an indispensable and precious factor in patient treatment planning to minimize the absorbed dose in vital tissues. In this study, compartmental model was used in order to estimate the human absorbed dose of ¹⁷⁷Lu-DOTATOC from the biodistribution data in wild type rats. For this purpose, ¹⁷⁷Lu-DOTATOC was prepared under optimized conditions and its biodistribution was studied in male Syrian rats up to 168 h. Compartmental model was applied to mathematical description of the drug behaviour in tissue at different times. Dosimetric estimation of the complex was performed using radiation absorbed dose assessment resource (RADAR). The biodistribution data showed high accumulation in the adrenal and pancreas as the major expression sites for somatostatin receptor (SSTR). While kidneys as the major route of excretion receive 0.037 mSv/MBq, pancreas and adrenal also obtain 0.039 and 0.028 mSv/MBq. Due to the usage of this method, the points of accumulated activity data were enhanced, and further information of tissues uptake was collected that it will be followed by high (or improved) precision in dosimetric calculations.

Keywords: compartmental modeling, human absorbed dose, ¹⁷⁷Lu-DOTATOC, Syrian rats

Procedia PDF Downloads 193

Authors: Ziyad S. Haidar

Abstract:

Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL), alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Opportunity: Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise and risk of immune reactions. For cases of dry sockets, specifically, the commercially-available and often-prescribed home remedies are highly lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Solution: Herein, SockGEL/PLUG (patent pending), an all-natural, drug-free and injectable stimuli-responsive hydrogel, was designed, formulated, characterized and evaluated as an osteogenic, angiogenic, anti-microbial and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in several oro-dental and cranio-maxillo-facial interventional applications; for example: in fresh dental extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (a) prevent the onset of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (b) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. Findings: The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physico-chemico-mechanically for safety (cell viability), viscosity, rheology, bio-distribution and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The performed animal model of cranial critical-sized and non-vascularized bone defects shall provide vitally critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease and speed in producing stable, biodegradable and sterilizable stimuli (thermo-sensitive and photo-responsive) matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for an intra-socket application, and beyond. Conclusions and Perspective: Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the bionanomaterial before engaging the market for feasibility, acceptance and cost-effectiveness studies. The SockGEL/PLUG platform is patent pending: SockGEL is a bio-inspired drug-free hydrogel; SockPLUG is a drug-loaded hydrogel designed for complex indications.

Keywords: hydrogel, injectable, dentistry, craniomaxillofacial complex, bioinspired, nanobiotechnology, biopolymer, sol-gel, stimuli-responsive, matrix, tissue engineering, regenerative medicine

Procedia PDF Downloads 72

Authors: Rui Chen, Jinfeng Zhang, Chun-Sing Lee

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In the past couple of decades, nanoscale metal-organic frameworks (NMOFs) have been highlighted as promising delivery platforms for biomedical applications, which combine many potent features such as high loading capacity, progressive biodegradability and low cytotoxicity. While NMOF has been extensively used as carriers for drugs of different modalities, so far there is no report on exploiting the advantages of NMOF for combination therapy. Herein, we prepared core-shell nanoparticles, where each nanoparticle contains a single graphitic-phase carbon nitride (g-C3N4) nanosheet encapsulated by a zeolitic-imidazolate frameworks-8 (ZIF-8) shell. The g-C3N4 nanosheets are effective visible-light photosensitizer for photodynamic therapy (PDT). When hosting DOX (doxorubicin), the as-synthesized core-shell nanoparticles could realize combinational photo-chemo therapy and provide dual-color fluorescence imaging. Therefore, we expect NMOFs-based core-shell nanoparticles could provide a new way to achieve much-enhanced cancer therapy.

Keywords: carbon nitride, combination therapy, drug delivery, nanoscale metal-organic frameworks

Procedia PDF Downloads 425

Authors: Palwinder Singh, Baljit Kaur, Sukhmeet Kaur

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Amongst a library of rationally designed small peptides, (H)Gly-Gly-Phe-Leu(OMe) was identified, reducing prostaglandin production of COX-2 with IC50 60 nM vs. 6000 nM for COX-1. The 5 mg Kg-1 dose of this compound rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of the compound for targeting COX-2, iNOS, and VGSC was investigated by using substances P, L-arginine, and veratrine, respectively, as the biomarkers. The interactions of the potent compound with COX-2 were supported by the isothermal calorimetry experiments showing Ka 6.10±1.10x104 mol-1 and ΔG -100.3 k J mol-1 in comparison to Ka 0.41x103 ±0.09 mol-1 and ΔG -19.2±0.06 k J mol-1 for COX-1. This compound did not show toxicity up to 2000 mg Kg-1 dose. Furthermore, beyond the conventional mode of working with anti-inflammatory agents through enzyme inhibition, COX-2 was provided with a peptide-based alternate substrate. Proline-centered pentapeptide iso-conformational to arachidonic acid exhibited appreciable selectivity for COX-2 overcoming acetic acid and formalin-induced pain in rats to almost 80% and was treated as a substrate by the enzyme. Hence, we suggest small peptides as highly potent and promising candidates for their further development into an anti-inflammatory drug.

Keywords: small peptides, cyclooxygenase, inflammation, substrate

Procedia PDF Downloads 88

Authors: Payal Mazumdar, Sunita Rattan, Monalisa Mukherjee

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Polymer nanocomposites are a special class of materials having unique properties and wide application in diverse areas such as EMI shielding, sensors, photovoltaic cells, membrane separation properties, drug delivery etc. Recently the nanocomposites are being investigated for their use in biomedical fields as biosensors. Though nanocomposites with carbon nanoparticles have received worldwide attention in the past few years, comparatively less work has been done on nanographite although it has in-plane electrical, thermal and mechanical properties comparable to that of carbon nanotubes. The main challenge in the fabrication of these nanocomposites lies in the establishment of homogeneous dispersion of nanographite in polymer matrix. In the present work, attempts have been made to synthesize the nanocomposites of polystyrene and nanographite using click chemistry. The polymer and the nanographite are functionalized prior to the formation of nanocomposites. The polymer, polystyrene, was functionalized with alkyne moeity and nanographite with azide moiety. The fabricating of the nanocomposites was accomplished through click chemistry using Cu (I)-catalyzed Huisgen dipolar cycloaddition. The functionalization of filler and polymer was confirmed by NMR and FTIR. The nanocomposites formed by the click chemistry exhibit better electrical properties and the sensors are evaluated for their application as biosensors.

Keywords: nanocomposites, click chemistry, nanographite, biosensor

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Authors: Aneta Nitsch-Osuch, Damian Okrucinski, Magdalena Dawgialło, Izabela Gołębiak, Ernest Kuchar

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The Hospital Antibiotic Policy (HAP) should be implemented to rationalize the antibiotic use and to decrease the risk of spreading of spreading of resistant bacteria. The aim of our study was to describe the antibiotic consumption patterns at the single oncosurgery ward before and after implementation of the HAP. We conducted a retrospective analysis of the antibiotic use at the Oncosurgery Ward in Warsaw (Poland) in years 2011-2016. Calculations were based on daily defined doses (DDDs), DDDs/100 hospitalizations and DDDs/100 person-days, drug utilization rates (DU 90% and DU 100%) were also analysed. After implementation of the HAP, the total antibiotic consumption increased (365.35 DDD in 2011 vs. 1359,22 DDD in 2016). The significant change was observed in antibiotic consumption patterns: the use of amoxicillin clavulanate and carbapenems or glycopeptides decreased significantly (p < 0,05), while the use of ciprofloxacin and aminoglycosides increased (p < 0,05). The DU100% rate varied from 6 in 2011 to 12 in 2016; while DU 90% rate varied from 2 in 2011 to 3-5 in 2013-2016. Although the implementation of the HAP did not result in the decreased total antibiotic consumption, it provided favorable changes in the antibiotic consumption patterns.

Keywords: antibiotics, hospital, policy, stewardship

Procedia PDF Downloads 247

Authors: Farah Ali, Tehreem Fiayyaz, Laeeq Akbar Lodhi, Imran Mirza

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The present work was undertaken to investigate effects of various extracts of W. somnifera (WS) for anti-diabetic activity in alloxan induced diabetic rabbits. Animals were divided into nine groups of six rabbits each. The animals of group 1 and 2 were given lactose (250 mg/kg, p.o) and WS root powder (100 mg/kg, p.o) respectively daily from day 1-20. Animals of group 3 were given alloxan (100 mg/kg, i.v) as a single dose on day 1. Powdered root of WS in the doses of 100, 150, 200 mg/kg and its aqueous (AWS) and ethanol extracts (EWS) (equivalent to 200 mg/kg of crude drug) were given to the treated animals (groups 4-8), respectively orally for three weeks (day 1-20 o.d), along with alloxan (100 mg/kg, i.v) as a single dose on day 1. Group 9 was given metformin (200 mg/kg) daily from day 1-20, along with a single dose of alloxan (100 mg/ kg, i.v) on day 1. Fasting serum glucose concentration in groups 3-9 was increased significantly (p<0.05) on day 3 as compared to normal control (NC) group (1). WS (100, 150, 200 mg/kg, p.o) decreased the fasting serum glucose concentration, with a maximum decrease (88.3 mg/dl) in group 2 (treated control) on day 21 of the experiment. These results indicate that metformin (reference control), (AWS) and (EWS) significantly antagonized the diabetic effects of alloxan.

Keywords: diabetes, serum, glucose, blood, sugar, rabbits

Procedia PDF Downloads 653

Authors: Pranporn Kuropakornpong, Srisopa Ruangnoo, Arunporn Itharat

Abstract:

Liver cancer has the highest prevalence rate in the North and Northeast of Thailand. Four Thai medicinal plants such as resin of Ferula asafoetida Regel, latex of Aloe barbadensis Miller leaves, roots of Baliospermum manotanum, and latex of Garcinia hanburyi Hook are used in Thai traditional medicine as cathartic drug and detoxification in liver cancer patients. Thus, this research aimed to evaluate the cytotoxic activity of these plants against hepatocarcinoma (HepG2) and cholangiocarcinoma (KKU-M156) cells by SRB assay. These plants were macerated in 95% ethanol. The results showed that roots of Baliospermum manotanum and latex of Garcinia hanburyi Hook showed the strongest cytotoxicity against HepG2 (IC50 = 3.03+0.91 and 0.62+0.01µg/ml, respectively) and KKU-M156 (IC50 = 0.978+0.663 and 0.006+0.005 µg/ml, respectively). Latex of Garcinia hanburyi Hook also showed high cytotoxicity against normal cell line (IC50=8.86+0.31 µg/ml), and even though its selective values are high, dose of this herb should be limited.

Keywords: cholangiocarcinoma, cytotoxic activity, Garcinia hanburyi Hook, hepatocarcinoma

Procedia PDF Downloads 451

Authors: S. Boulenouar, M. Sefir, M. Benahmed

Abstract:

All facilities need medication and other pharmaceuticals for their operation. Management and supply is therefore to provide the different services of the facility goods and services in required quantity and quality. The permanent availability of drugs in the facilities is very difficult because most face many difficulties at the inventory management and drug supplies. Therefore, it is necessary for each health facility to know the causes for the malfunction of its management system to cope with them. It is in this context that we have undertaken to conduct this study to know the causes which should be taken into consideration by the concerned authorities to carry out their mission, which is to provide quality health care for the population. In terms of financial resources, the budget for medicines represents a significant part of the budget of the pharmacy. Our study shows that the share of the hospital budget reserved for the drugs procurement represent on average 70% of the budget of the pharmacy. The results show a state of lack of anticancer drugs at Oran teaching hospital. The analysis of the management process allowed us to know the level that the problem of stock-outs of anti-cancer drugs is at. Suggestions were made to that effect to improve the availability for these products and to respond better to the needs of patients.

Keywords: anticancer drugs, health care facility, budget, hospital pharmacist, hospital service

Procedia PDF Downloads 446

Authors: M. R. Phadatare, J. V. Meshram, S. H. Pawar

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Conversion of electromagnetic energy into heat by nanoparticles (NPs) has the potential to be a powerful, non-invasive technique for biomedical applications such as magnetic fluid hyperthermia, drug release, disease treatment and remote control of single cell functions, but poor conversion efficiencies have hindered practical applications so far. In this paper, an attempt has been made to increase the efficiency of magnetic, thermal induction by NPs. To increase the efficiency of magnetic, thermal induction by NPs, one can take advantage of the exchange coupling between a magnetically hard core and magnetically soft shell to tune the magnetic properties of the NP and maximize the specific absorption rate, which is the gauge of conversion efficiency. In order to examine the tunability of magnetocrystalline anisotropy and its magnetic heating power, a representative magnetically hard material (CoFe₂O₄) has been coupled to a soft material (Ni₀.₅Zn₀.₅Fe₂O₄). The synthesized NPs show specific absorption rates that are of an order of magnitude larger than the conventional one.

Keywords: magnetic nanoparticles, surface functionalization of magnetic nanoparticles, magnetic fluid hyperthermia, specific absorption rate

Procedia PDF Downloads 320