Search results for: drug diffusion

Authors: Mounir Kehal

Abstract:

The post-globalization epoch has placed businesses everywhere in new and different competitive situations where knowledgeable, effective and efficient behavior has come to provide the competitive and comparative edge. Enterprises have turned to explicit - and even conceptualizing on tacit - knowledge management to elaborate a systematic approach to develop and sustain the intellectual capital needed to succeed. To be able to do that, you have to be able to visualize your organization as consisting of nothing but knowledge and knowledge flows, whilst being presented in a graphical and visual framework, referred to as automated organizational cartography. Hence, creating the ability of further actively classifying existing organizational content evolving from and within data feeds, in an algorithmic manner, potentially giving insightful schemes and dynamics by which organizational know-how is visualized. It is discussed and elaborated on most recent and applicable definitions and classifications of knowledge management, representing a wide range of views from mechanistic (systematic, data driven) to a more socially (psychologically, cognitive/metadata driven) orientated. More elaborate continuum models, for knowledge acquisition and reasoning purposes, are being used for effectively representing the domain of information that an end user may contain in their decision making process for utilization of available organizational intellectual resources (i.e. Autocart). In this paper, we present an empirical research study conducted previously to try and explore knowledge diffusion in a specialist knowledge domain.

Keywords: knowledge management, knowledge maps, knowledge diffusion, organizational cartography

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Authors: Lichung Jen, Yi Chun Liu, Kuan-Wei Lee

Abstract:

Fruitful data has been accumulated in database nowadays and is commonly used as support for decision-making. In the healthcare industry, hospital, for instance, ordering pharmacy inventory is one of the key decision. With large drug inventory, the current cost increases and its expiration dates might lead to future issue, such as drug disposal and recycle. In contrast, underestimating demand of the pharmacy inventory, particularly standing drugs, affects the medical treatment and possibly hospital reputation. Prescription behaviour of hospital physicians is one of the critical factor influencing this decision, particularly irregular prescription behaviour. If a drug’s usage amount in the month is irregular and less than the regular usage, it may cause the trend of subsequent stockpiling. On the contrary, if a drug has been prescribed often than expected, it may result in insufficient inventory. We proposed a hierarchical Bayesian mixture model with two components to identify physicians’ regular/irregular prescription patterns with probabilities. Heterogeneity of hospital is considered in our proposed hierarchical Bayes model. The result suggested that modeling the prescription patterns of physician is beneficial for estimating the order quantity of medication and pharmacy inventory management of the hospital. Managerial implication and future research are discussed.

Keywords: hierarchical Bayesian model, poission mixture model, medicines prescription behavior, irregular behavior

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Authors: Amanda C. Q. M. Vieira, Cybelly M. Melo, Camila B. M. Figueirêdo, Giovanna C. R. M. Schver, Salvana P. M. Costa, Magaly A. M. de Lyra, Ping I. Lee, José L. Soares-Sobrinho, Pedro J. Rolim-Neto, Mônica F. R. Soares

Abstract:

Epiisopiloturine (EPI) is a drug candidate that is extracted from Pilocarpus microphyllus and isolated from the waste of Pilocarpine. EPI has demonstrated promising schistosomicidal, leishmanicide, anti-inflammatory and antinociceptive activities, according to in vitro studies that have been carried out since 2009. However, this molecule shows poor aqueous solubility, which represents a problem for the release of the drug candidate and its absorption by the organism. The purpose of the present study is to investigate the extent of enhancement of kinetic solubility of a solid solution (SS) of EPI in hipromellose phthalate HP-55 (HPMCP), an enteric polymer carrier. SS was obtained by the solvent evaporation methodology, using acetone/methanol (60:40) as solvent system. Both EPI and polymer (drug loading 10%) were dissolved in this solvent until a clear solution was obtained, and then dried in oven at 60ºC during 12 hours, followed by drying in a vacuum oven for 4 h. The results show a considerable modification in the crystalline structure of the drug candidate. For instance, X-ray diffraction (XRD) shows a crystalline behavior for the EPI, which becomes amorphous for the SS. Polarized light microscopy, a more sensitive technique than XRD, also shows completely absence of crystals in SS sample. Differential Scanning Calorimetric (DSC) curves show no signal of EPI melting point in SS curve, indicating, once more, no presence of crystal in this system. Interaction between the drug candidate and the polymer were found in Infrared microscopy, which shows a carbonyl 43.3 cm-1 band shift, indicating a moderate-strong interaction between them, probably one of the reasons to the SS formation. Under sink conditions (pH 6.8), EPI SS had its dissolution performance increased in 2.8 times when compared with the isolated drug candidate. EPI SS sample provided a release of more than 95% of the drug candidate in 15 min, whereas only 45% of EPI (alone) could be dissolved in 15 min and 70% in 90 min. Thus, HPMCP demonstrates to have a good potential to enhance the kinetic solubility profile of EPI. Future studies to evaluate the stability of SS are required to conclude the benefits of this system.

Keywords: epiisopiloturine, hipromellose phthalate HP-55, pharmaceuticaltechnology, solubility

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Authors: Noshaba Dilbar, Hina Ashraf

Abstract:

Medicinal plants are considered as rich source of ingredients which can be used in drug development and synthesis. Moreover, these plants play a vital role in the development of human culture of using ayurvedic medicines around the whole world. Among all plants, dessert plants are being proved as effective source of ayurvedic medicines and remedy against many diseases. Considering the fact, two plant species Limium indicum and Euphorbia granulata were taken from Cholistan dessert of Bahawalpur, Pakistan. Firstly, phytochemical screening was done by making dry and fresh plant extracts in five different solvents i.e Petroleum ether, benzene, chloroform, ethanol and methanol. Standard confirmation tests for all compounds were applied for analysis. Results revealed the presence of high range of bioactive compounds such as alakaloids, terpenoids, glycosides, steroids, flavonoids, saponins, phytosterols, oxalic acid, anthocyanin and quinone in both plants. Best results were obtained by methanolic, chloroform and petroleum ether extracts and methanolic, ethanolic and benzene extracts of Limium indicum and Euphorbia granulate respectively. Considering the results, methanolic extracts of both plants were further analysed for antibacterial activity. Plants were analysed against four pathogens including Escherchia coli, Proteus vulgaris, Klebsiella pneumonia and Pseudomonas aruginosa using disc diffusion method. Limium indicum showed highly significant activity against all pathogens while Euphorbia granulata showed significant activity against Klebsiella pneumonia and Proteus vulgaris but lesser against Escherchia coli and Pseudomonas aruginosa. MIC of extracts against each positive bacterium was calculated and recorded. Present plants can be considered for making useful drugs but further studies are needed to isolate active agents from plant extracts for drug development.

Keywords: antibacterial activity, Euphorbia granulata, Limium indicum, medicinal plants, phytochemical screening

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Authors: Tadesse Melaku Abegaz

Abstract:

Background: there was paucity of data on the self-reported adverse drug reactions (ADRs), level of adherence and clinical outcomes with antidepressants among major depressive disorder (MDD) patients in Ethiopia. Hence, the present study sought to determine the level of adherence for and clinical outcome with antidepressants and the magnitude of ADRs. Methods: A prospective cross-sectional study was employed on MDD patients from September 2016 to January 2017 at Gondar university hospital psychiatry clinic. All patients who were available during the study period were included under the study population. The Naranjo adverse drug reaction probability scale was employed to assess the adverse drug reaction. The rate of medication adherence was determined using morisky medication adherence measurement scale eight. Clinical Outcome of patients was measured by using patient health questionnaire. Multivariable logistic carried out to determine factors for adherence and patient outcome. Results: two hundred seventy patients were participated in the study. More than half of the respondents were males 122(56.2%). The mean age of the participants was 30.94 ± 8.853. More than one-half of the subjects had low adherence to their medications 124(57.1%). About 186(85.7%) of patients encountered ADR. The most common ADR was weight gain 29(13.2). Around 198(92.2%) ADRs were probable and 19(8.8%) were possible. Patients with long standing MDD had high risk of non-adherence COR: 2.458[4.413-4.227], AOR: 2.424[1.185-4.961]. More than one-half 125(57.6) of respondents showed improved outcome. Optimal level of medication adherence was found to be associated with reduced risk of progression of the diseases COR: 0.37[0.110-5.379] and AOR: 0.432[0.201-0.909]. Conclusion: Patient reported adverse drug reactions were more prevalent in major depressive disorder patients. Adherence to medications was very poor in the setup. However, the clinical outcome was relatively higher. Long standing depression was associated with non-adherence. In addition, clinical outcome of patients were affected by non-adherence. Therefore, adherence enhancing interventions should be provided to improve medication adherence and patient outcome.

Keywords: adverse drug reactions, clinical outcomes, Ethiopia, prospective study, medication adherence

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Authors: Jinfeng Zhang, Chun-Sing Lee

Abstract:

Pure nanodrugs (PNDs) – nanoparticles consisting entirely of drug molecules, have been considered as promising candidates for the next-generation nanodrugs. However, the traditional preparation method via reprecipitation faces critical challenges including low production rates, relatively large particle sizes and batch-to-batch variations. Here, for the first time, we successfully developed a novel, versatile and controllable strategy for preparing PNDs via an anodized aluminium oxide (AAO) template-assisted method. With this approach, we prepared PNDs of an anti-cancer drug (VM-26) with precisely controlled sizes reaching the sub-20 nm range. This template-assisted approach has much higher feasibility for mass production comparing to the conventional reprecipitation method and is beneficial for future clinical translation. The present method is further demonstrated to be easily applicable for a wide range of hydrophobic biomolecules without the need of custom molecular modifications and can be extended for preparing all-in-one nanostructures with different functional agents.

Keywords: drug delivery, pure nanodrugs, size control, template

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Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, C. V. Rao

Abstract:

Elvitegravir is the mainstay of anti-HIV combination therapy in most endemic countries presently. However, it cannot be used alone owing to its long onset time of action. 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one (Quercetin: QU) is a polyphenolic compound obtained from Argeria speciosa Linn (Family: Convolvulaceae), an anti-HIV candidate. In the present study, a sensitive, simple and rapid high-performance liquid chromatography coupled with positive ion electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the simultaneous determination elvitegravir and Quercetin, in rat plasma. The method was linear over a range of 0.2–500 ng/ml. All validation parameters met the acceptance criteria according to regulatory guidelines. LC–MS/MS method for determination of Elvitegravir and Quercetin was developed and validated. Results show the potential of drug–drug interaction upon co-administration this marketed drugs and plant derived secondary metabolite.

Keywords: anti-HIV resistance, extraction, HPLC-ESI-MS-MS, validation

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Authors: Kianoosh Samimi, Siham Kamali-Bernard, Ali Akbar Maghsoudi

Abstract:

This paper aims to contribute to the characterization and the understanding of fresh state, compressive strength and chloride penetration tendency of high strength self-compacting concretes (HSSCCs) where Portland cement type II is partially substituted by 10% and 15% of natural pumice and zeolite. First, five concrete mixtures with a control mixture without any pozzolan are prepared and tested in both fresh and hardened states. Then, resistance to chloride penetration for all formulation is investigated in non-steady state and steady state by measurement of chloride penetration and diffusion coefficient. In non-steady state, the correlation between initial current and chloride penetration with diffusion coefficient is studied. Moreover, the relationship between diffusion coefficient in non-steady state and electrical resistivity is determined. The concentration of free chloride ions is also measured in steady state. Finally, chloride penetration for all formulation is studied in immersion and tidal condition. The result shows that, the resistance to chloride penetration for HSSCC in immersion and tidal condition increases by incorporating pumice and zeolite. However, concrete with zeolite displays a better resistance. This paper shows that the HSSCC with 15% pumice and 10% zeolite is suitable in fresh, hardened, and durability characteristics.

Keywords: Chloride penetration, immersion, pumice, HSSCC, tidal, zeolite

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Authors: Said Abdirasak Abidrahman, Ibrahim Mohamed

Abstract:

Background: Urinary Tract Infections (UTIs) are the commonest infections described among diabetes mellitus patients. More often, empirical antimicrobial therapy is initiated before the laboratory results are made available with minimal treatment success. The knowledge of the etiology and antibiotic susceptibility patterns of the organisms causing urinary tract infections among diabetes mellitus patients remains scarce, despite its vitality. This study sought to determine the prevalence, bacteria species, and drug susceptibility patterns of common causes of urinary tract infections among diabetes mellitus patients attending Bosaso health centers. Materials and methods: We conducted a cross-sectional study involving adult diabetic patients at Bosaso health centers between the months of May and July 2020. Laboratory assay of mid-stream urine samples was done to isolate bacteria causes of UTIs. These were biochemically identified using Gram stain, Kligler iron agar (KIA), Indole test, citrate, urea, coagulase, catalase, motility agar, and lysine iron agar. Their antibiotic susceptibility pattern for the isolated organisms was made for Ampicillin 10μg, Ciprofloxacin 5μg, Cotrimoxazole 25μg, Gentamycin 10μg, Ceftriaxone 10μg, and determined using the Kirby Bauer Disc Diffusion method. Results: Of 177 participants, 69 (39.0%) were males and 108 (61.0%) were females. Their mean age was 33.1 years (range; 18-67 years). Of these, 14.7% (26/177) of the samples revealed significant growth (>= 105 CFU/mL) giving a prevalence of 14.9 % (95% CI: 10.6 to 16.3). The organisms isolated were Escherichia coli -50% (N=13), Klebsiella pneumonia 30.8% (N=8), Staphylococcus aureus 15.4% (N=4), and unidentified organism 3.8% (N=1), and these were associated with such socio-demographic factors like history of catheterization and sexual activity. Antibiotic susceptibility to the commonly used agents for treating UTIs indicated higher sensitivity to Gentamicin and Ceftriaxone.

Keywords: antimicrobials, bacteria, urinary tract infections, diabetes

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Authors: Yohanes Chekol Malede

Abstract:

σ-phase has negative effects on the corrosion responses and the mechanical properties of steels. The growth of σ-phase in the austenite matrix of AISI 347H FG steel was simulated using DICTRA software using CALPHAD method. The simulation work included the influence of both volume diffusion and grain boundary diffusion. The simulation results showed a good agreement with the experimental findings. The simulation results revealed a Cr-depleted and a Ni-enriched σ-phase/austenite interface. Effects of temperature, grain size, and composition of alloying elements on the growth kinetics of σ-phase were assessed. The simulated results were fitted to the JMAK equation and a good correlation was obtained.

Keywords: AISI 347H FG austenitic steel, CALPHAD, sigma phase, microstructure evolution

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers

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Authors: Mounir Kehal, Adel Al Araifi

Abstract:

The post-globalisation epoch has placed businesses everywhere in new and different competitive situations where knowledgeable, effective and efficient behaviour has come to provide the competitive and comparative edge. Enterprises have turned to explicit- and even conceptualising on tacit- Knowledge Management to elaborate a systematic approach to develop and sustain the Intellectual Capital needed to succeed. To be able to do that, you have to be able to visualize your organization as consisting of nothing but knowledge and knowledge flows, whilst being presented in a graphical and visual framework, referred to as automated organizational cartography. Hence, creating the ability of further actively classifying existing organizational content evolving from and within data feeds, in an algorithmic manner, potentially giving insightful schemes and dynamics by which organizational know-how is visualised. It is discussed and elaborated on most recent and applicable definitions and classifications of knowledge management, representing a wide range of views from mechanistic (systematic, data driven) to a more socially (psychologically, cognitive/metadata driven) orientated. More elaborate continuum models, for knowledge acquisition and reasoning purposes, are being used for effectively representing the domain of information that an end user may contain in their decision making process for utilization of available organizational intellectual resources (i.e. Autocart). In this paper we present likewise an empirical research study conducted previously to try and explore knowledge diffusion in a specialist knowledge domain.

Keywords: knowledge management, knowledge maps, knowledge diffusion, organizational cartography

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Authors: Huafeng Wei

Abstract:

Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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Authors: Anyimc, C. J. Aneke, J. O. Orji, O. Nworie, U. C. C. Egbule

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The microbial examination and antimicrobial susceptibility profile of microorganism isolated from the salt mining site in Ebonyi state were evaluated in the present study using a standard microbiological technique. A total of 300 samples were randomly collected in three sample groups (A, B, and C) of 100 each. Isolation, Identification and characterization of organization present on the soil samples were determined by culturing, gram-staining and biochemical technique. The result showed the following organisms were isolated with their frequency as follow: Bacillus species (37.3%) and Staphylococcus species(23.5%) had the highest frequency in the whole Sample group A and B while Klebsiella specie (15.7%), Pseudomonas species(13.7%), and Erwinia species (9.8%) had the least. Rhizopus species (42.0%) and Aspergillus species (26.0%) were the highest fungi isolated, followed by Penicillum species (20.0%) while Mucor species (4.0%), and Fusarium species (8.0%) recorded the least. Sample group C showed high microbial population of all the microbial isolates when compared to sample group A and B. Disc diffusion method was used to determine the susceptibility of isolated bacteria to various antibiotics (oxfloxacin, pefloxacin, ciprorex, augumentin, gentamycin, ciproflox, septrin, ampicillin), while agar well diffusion method was used to determine the susceptibility of isolated fungi to some antifungal drugs (metronidazole, ketoconazole, itraconazole fluconazole). The antibacterial activity of the antibiotics used showed that ciproflux has the best inhibitory effect on all the test bacteria. Ketoconazole showed the highest inhibitory effect on the fungal isolates, followed by itraconazole, while metronidazole and fluconazole showed the least inhibitory effect on the entire test fungal isolates. Hence, the multiple drug resistance of most isolates to appropriate drugs of choice are of great public health concern and cells for periodic monitoring of antibiograms to detect possible changing patterns. Microbes isolated in the salt mining site can also be used as a source of gene(s) that can increase salt tolerance in different crop species through genetic engineering.

Keywords: microorganisms, antibacterial, antifungal, resistance, salt mining site, Ebonyi State

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Authors: Afshin Zohdi, Selçuk Özdemir, Mustafa Aksoy

Abstract:

Tungsten carbide-cobalt (WC-Co) is a widely utilized material for cold forming dies, including those employed in fastener production. In this study, we investigated the effectiveness of the pack boriding method in improving the surface properties of WC-Co cold forging dies. The boriding process involved embedding WC-Co samples, along with a steel control sample, within a chamber made of H13 tool steel. A boriding powder mixture was introduced into the chamber, which was then sealed using a paste. Subsequently, the samples were subjected to a temperature of 700°C for 5 hours in a furnace. Microstructural analysis, including cross-sectional examination and scanning electron microscopy (SEM), confirmed successful boron diffusion and its presence on the surface of the borided samples. The microhardness of the borided layer was significantly increased (3980 HV1) compared to the unborided sample (1320 HV3), indicating enhanced hardness. The borided layer exhibited an acceptable thickness of 45 microns, with a diffusion coefficient of 1.125 × 10-7 mm²/s, signifying a moderate diffusion rate. Energy-dispersive X-ray spectroscopy (EDS) mapping revealed an increase in boron content, desirable for the intended purpose, while an undesired increase in oxygen content was observed. Furthermore, the pin-on-disk wear test demonstrated a reduction in friction coefficient, indicating improved mechanical and tribological properties of the surface. The successful implementation of the pack boriding process highlights its potential for enhancing the performance of WC-Co cold forging dies.

Keywords: WC-Co, cold forging dies, pack boriding, surface hardness, wear resistance, microhardness, diffusion coefficient, scanning electron microscopy, energy-dispersive X-ray spectroscopy

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Authors: Zhi Hao Chow, Cian Mulligan, Jack Walsh, Antonio Garzon Vico, Dimitar Krastev

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Drug development is resource-intensive, time-consuming, and increasingly expensive with each developmental stage. The success rates of drug development are also relatively low, and the resources committed are wasted with each failed candidate. As such, a reliable method of predicting the success of drug development is in demand. The hypothesis was that some examples of failed drug candidates are pushed through developmental pipelines based on false confidence and may possess common linguistic features identifiable through sentiment analysis. Here, the concept of using text analysis to discover such features in research publications and investor reports as predictors of success was explored. R studios were used to perform text mining and lexicon-based sentiment analysis to identify affective phrases and determine their frequency in each document, then using SPSS to determine the relationship between our defined variables and the accuracy of predicting outcomes. A total of 161 publications were collected and categorised into 4 groups: (i) Cancer treatment, (ii) Neurodegenerative disease treatment, (iii) Vaccines, and (iv) Others (containing all other drugs that do not fit into the 3 categories). Text analysis was then performed on each document using 2 separate datasets (BING and AFINN) in R within the category of drugs to determine the frequency of positive or negative phrases in each document. A relative positivity and negativity value were then calculated by dividing the frequency of phrases with the word count of each document. Regression analysis was then performed with SPSS statistical software on each dataset (values from using BING or AFINN dataset during text analysis) using a random selection of 61 documents to construct a model. The remaining documents were then used to determine the predictive power of the models. Model constructed from BING predicts the outcome of drug performance in clinical trials with an overall percentage of 65.3%. AFINN model had a lower accuracy at predicting outcomes compared to the BING model at 62.5% but was not effective at predicting the failure of drugs in clinical trials. Overall, the study did not show significant efficacy of the model at predicting outcomes of drugs in development. Many improvements may need to be made to later iterations of the model to sufficiently increase the accuracy.

Keywords: data analysis, drug development, sentiment analysis, text-mining

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Authors: X. King, E. Nazarzadeh, J. Reboud, J. Cooper

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Pulmonary diseases, such as asthma, are generally treated by the inhalation of aerosols that has the advantage of reducing the off-target (e.g., toxicity) effects associated with systemic delivery in blood. Effective respiratory drug delivery requires a droplet size distribution between 1 and 5 µm. Inhalation of aerosols with wide droplet size distribution, out of this range, results in deposition of drug in not-targeted area of the respiratory tract, introducing undesired side effects on the patient. In order to solely deliver the drug in the lower branches of the lungs and release it in a targeted manner, a control mechanism to produce the aerosolized droplets is required. To regulate the drug release and to facilitate the uptake from cells, drugs are often encapsulated into protective liposomes. However, a multistep process is required for their formation, often performed at the formulation step, therefore limiting the range of available drugs or their shelf life. Using surface acoustic waves (SAWs), a pulmonary drug delivery platform was produced, which enabled the formation of defined size aerosols and the formation of liposomes in situ. SAWs are mechanical waves, propagating along the surface of a piezoelectric substrate. They were generated using an interdigital transducer on lithium niobate with an excitation frequency of 9.6 MHz at a power of 1W. Disposable silicon superstrates were etched using photolithography and dry etch processes to create an array of cylindrical through-holes with different diameters and pitches. Superstrates were coupled with the SAW substrate through water-based gel. As the SAW propagates on the superstrate, it enables nebulisation of a lipid solution deposited onto it. The cylindrical cavities restricted the formation of large drops in the aerosol, while at the same time unilamellar liposomes were created. SAW formed liposomes showed a higher monodispersity compared to the control sample, as well as displayed, a faster production rate. To test the aerosol’s size, dynamic light scattering and laser diffraction methods were used, both showing the size control of the aerosolised particles. The use of silicon superstate with cavity size of 100-200 µm, produced an aerosol with a mean droplet size within the optimum range for pulmonary drug delivery, containing the liposomes in which the medicine could be loaded. Additionally, analysis of liposomes with Cryo-TEM showed formation of vesicles with narrow size distribution between 80-100 nm and optimal morphology in order to be used for drug delivery. Encapsulation of nucleic acids in liposomes through the developed SAW platform was also investigated. In vitro delivery of siRNA and DNA Luciferase were achieved using A549 cell line, lung carcinoma from human. In conclusion, SAW pulmonary drug delivery platform was engineered, in order to combine multiple time consuming steps (formation of liposomes, drug loading, nebulisation) into a unique platform with the aim of specifically delivering the medicament in a targeted area, reducing the drug’s side effects.

Keywords: acoustics, drug delivery, liposomes, surface acoustic waves

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Authors: Wangxu Xia

Abstract:

BACKGROUND BI-RADS 4 lesions raise the possibility of malignancy that warrant further clinical and radiologic work-up. This study aimed to evaluate the predictive performance of diffusion-weighted imaging(DWI) and microcalcifications on mammography for predicting malignancy of BI-RADS 4 lesions. In addition, the predictive performance of DWI combined with microcalcifications was alsocompared with the Kaiser score. METHODS During January 2021 and June 2023, 144 patients with 178 BI-RADS 4 lesions underwent conventional MRI, DWI, and mammography were included. The lesions were dichotomized intobenign or malignant according to the pathological results from core needle biopsy or surgical mastectomy. DWI was performed with a b value of 0 and 800s/mm2 and analyzed using theapparent diffusion coefficient, and a Kaiser score > 4 was considered to suggest malignancy. Thediagnostic performances for various diagnostic tests were evaluated with the receiver-operatingcharacteristic (ROC) curve. RESULTS The area under the curve (AUC) for DWI was significantly higher than that of the of mammography (0.86 vs 0.71, P<0.001), but was comparable with that of the Kaiser score (0.86 vs 0.84, P=0.58). However, the AUC for DWI combined with mammography was significantly highthan that of the Kaiser score (0.93 vs 0.84, P=0.007). The sensitivity for discriminating malignant from benign BI-RADS 4 lesions was highest at 89% for Kaiser score, but the highest specificity of 83% can be achieved with DWI combined with mammography. CONCLUSION DWI combined with microcalcifications on mammography could discriminate malignant BI-RADS4 lesions from benign ones with a high AUC and specificity. However, Kaiser score had a better sensitivity for discrimination.

Keywords: MRI, DWI, mammography, breast disease

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Authors: Reinhold Kosfeld, Andreas Gohs

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In the reduction of CO₂ emissions, the transition to environmentally friendly transport modes has a high significance. In Germany, the climate protection programme 2030 includes various measures for promoting electromobility. Although electric cars at present hold a market share of just over one percent, its stock more than doubled in the past two years. Special measures like tax incentives and a buyer’s premium have been put in place to promote the shift towards electric cars and boost their diffusion. Knowledge of the future expansion of electric cars is required for planning purposes and adaptation measures. With a view of these objectives, we particularly investigate the effect of spatial spillovers on forecasting performance. For this purpose, time series econometrics and panel econometric models are designed for pure electric cars and hybrid cars for Germany. Regional forecasting models with spatial interactions are consistently estimated by using spatial econometric techniques. Regional data on the stocks of electric cars and their determinants at the district level (NUTS 3 regions) are available from the Federal Motor Transport Authority (Kraftfahrt-Bundesamt) for the period 2017 - 2019. A comparative examination of aggregated regional and national predictions provides quantitative information on accuracy gains by allowing for spatial spillovers in forecasting electric mobility.

Keywords: electric mobility, forecasting market diffusion, regional panel data model, spatial interaction

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Authors: Minh-Phuong Ngoc Bui, Abdennour Abbas

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Microbial spoilage of food/drug has been a constant nuisance and an unavoidable problem throughout history that affects food/drug quality and safety in a variety of ways. A simple and rapid test of fungi and bacteria in food/drugs and environmental clinical samples is essential for proper management of contamination. A number of different techniques have been developed for detection and enumeration of foodborne microorganism including plate counting, enzyme-linked immunosorbent assay (ELISA), polymer chain reaction (PCR), nucleic acid sensor, electrical and microscopy methods. However, the significant drawbacks of these techniques are highly demand of operation skills and the time and cost involved. In this report, we introduce a rapid method for detection of bacteria and fungi in food/drug products using a specific interaction between a reducing agent (tris(2-carboxylethyl)phosphine (TCEP)) and the microbial surface proteins. The chemical reaction was transferred to a transduction system using gold nanoplates-enhanced chemiluminescence. We have optimized our nanoplates synthetic conditions, characterized the chemiluminescence parameters and optimized conditions for the microbial assay. The new detection method was applied for rapid detection of bacteria (E.coli sp. and Lactobacillus sp.) and fungi (Mucor sp.), with limit of detection as low as single digit cells per mL within 10 min using a portable luminometer. We expect our simple and rapid detection method to be a powerful alternative to the conventional plate counting and immunoassay methods for rapid screening of microorganisms in food/drug products.

Keywords: microorganism testing, gold nanoplates, chemiluminescence, reducing agents, luminol

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Authors: Hamida Hamed Said Al Harthi

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Background: Illegal drug use is a rising problem that affects Omani youth. This research aimed to study a group of young Omani men who were imprisoned more than once for illegal drug use, focusing on exploring their lifestyle experiences inside and outside the prison and whether these contributed to their early relapse and re-imprisonment. This is the first study of its kind from Oman conducted in a prison setting. Methods: 19 Omani males aged 18–35 years imprisoned in Oman Central Prison were recruited using purposive sampling. Focused ethnography was conducted over 8 months to explore the drug-related experiences outside the prison and during imprisonment. Face-to-face semi-structured interviews with the participants yielded detailed transcripts and field notes. These were thematically analyzed, and the results were compared with the existing literature. Results: The participants’ voices yielded new insights into the lives of young Omani men imprisoned for illegal drug use, including their sufferings and challenges in prison. These included: entry shock, timing and boredom, drug trafficking in prison, as well as physical and psychological health issues. Overall, imprisonment was reported to have negatively impacted the participants’ health, personality, self-concept, emotions, attitudes, behavior and life expectations. The participants reported how their efforts to reintegrate into the Omani community after release from prison were rebuffed due to stigmatization and rejection from society and family. They also experienced frequent unemployment, police surveillance, accommodation problems and a lack of rehabilitation facilities. The immensity of the accumulated psychophysiological trauma contributed to their early relapse and re-imprisonment. Conclusion: This thesis concludes that imprisonment is largely ineffective in controlling drug use in Oman. Urgent action is required across multiple sectors to improve the lives and prospects of users of illegal drugs within and outside the prison to minimize factors contributing to early relapse. Key Words: illegal drugs, drug users, Oman, addiction, Omani culture, prisoners, relapse, re-imprisonment, qualitative research, ethnography.

Keywords: illigal drugs, Prison, Omani culture lifestyle, post prison life

Procedia PDF Downloads 64

Authors: Lacramioara Ochiuz, Aurelia Vasile, Iulian Stoleriu, Cristina Ghiciuc, Maria Ignat

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Topical administration of chemotherapeutic agents (eg. carmustine, bexarotene, mechlorethamine etc.) in local treatment of cutaneous T-cell lymphoma (CTCL) is accompanied by multiple side effects, such as contact hypersensitivity, pruritus, skin atrophy or even secondary malignancies. A known method of reducing the side effects of anticancer agent is the development of modified drug release systems using drug incapsulation in biocompatible nanoporous inorganic matrices, such as mesoporous MCM-41 silica. Mesoporous MCM-41 silica is characterized by large specific surface, high pore volume, uniform porosity, and stable dispersion in aqueous medium, excellent biocompatibility, in vivo biodegradability and capacity to be functionalized with different organic groups. Therefore, MCM-41 is an attractive candidate for a wide range of biomedical applications, such as controlled drug release, bone regeneration, protein immobilization, enzymes, etc. The main advantage of this material lies in its ability to host a large amount of the active substance in uniform pore system with adjustable size in a mesoscopic range. Silanol groups allow surface controlled functionalization leading to control of drug loading and release. This study shows (I) the amino-grafting optimization of mesoporous MCM-41 silica matrix by means of co-condensation during synthesis and post-synthesis using APTES (3-aminopropyltriethoxysilane); (ii) loading the therapeutic agent (carmustine) obtaining a modified drug release systems; (iii) determining the profile of in vitro carmustine release from these systems; (iv) assessment of carmustine release kinetics by fitting on four mathematical models. Obtained powders have been described in terms of structure, texture, morphology thermogravimetric analysis. The concentration of the therapeutic agent in the dissolution medium has been determined by HPLC method. In vitro dissolution tests have been done using cell Enhancer in a 12 hours interval. Analysis of carmustine release kinetics from mesoporous systems was made by fitting to zero-order model, first-order model Higuchi model and Korsmeyer-Peppas model, respectively. Results showed that both types of highly ordered mesoporous silica (amino grafted by co-condensation process or post-synthesis) are thermally stable in aqueous medium. In what regards the degree of loading and efficiency of loading with the therapeutic agent, there has been noticed an increase of around 10% in case of co-condensation method application. This result shows that direct co-condensation leads to even distribution of amino groups on the pore walls while in case of post-synthesis grafting many amino groups are concentrated near the pore opening and/or on external surface. In vitro dissolution tests showed an extended carmustine release (more than 86% m/m) both from systems based on silica functionalized directly by co-condensation and after synthesis. Assessment of carmustine release kinetics revealed a release through diffusion from all studied systems as a result of fitting to Higuchi model. The results of this study proved that amino-functionalized mesoporous silica may be used as a matrix for optimizing the anti-cancer topical therapy by loading carmustine and developing prolonged-release systems.

Keywords: carmustine, silica, controlled, release

Procedia PDF Downloads 243

Authors: Abhay Asthana, Gyati Shilakari Asthana

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It’s the patient compliance and stability in combination with controlled drug delivery and biocompatibility that forms the core feature in present research and development of sustained biodegradable patch formulation intended for wound healing. The aim was to impart sustained degradation, sterile formulation, significant folding endurance, elasticity, biodegradability, bio-acceptability and strength. The optimized formulation was developed using component including polymers including Hydroxypropyl methyl cellulose, Ethylcellulose, and Gelatin, and Citric Acid PEG Citric acid (CPEGC) triblock dendrimers and active Curcumin. Polymeric mixture dissolved in geometric order in suitable medium through continuous stirring under ambient conditions. With continued stirring Curcumin was added with aid of DCM and Methanol in optimized ratio to get homogenous dispersion. The dispersion was sonicated with optimum frequency and for given time and later casted to form a patch form. All steps were carried out under under strict aseptic conditions. The formulations obtained in the acceptable working range were decided based on thickness, uniformity of drug content, smooth texture and flexibility and brittleness. The patch kept on stability using butter paper in sterile pack displayed folding endurance in range of 20 to 23 times without any evidence of crack in an optimized formulation at room temperature (RT) (24 ± 2°C). The patch displayed acceptable parameters after stability study conducted in refrigerated conditions (8±0.2°C) and at RT (24 ± 2°C) upto 90 days. Further, no significant changes were observed in critical parameters such as elasticity, biodegradability, drug release and drug content during stability study conducted at RT 24±2°C for 45 and 90 days. The drug content was in range 95 to 102%, moisture content didn’t exceeded 19.2% and patch passed the content uniformity test. Percentage cumulative drug release was found to be 80% in 12h and matched the biodegradation rate as drug release with correlation factor R2>0.9. The biodegradable patch based formulation developed shows promising results in terms of stability and release profiles.

Keywords: sustained biodegradation, wound healing, polymers, stability

Procedia PDF Downloads 323

Authors: Alok Shiomurti Tripathi, Ajay Kumar Timiri, Papiya Mitra Mazumder, Anil Chandewar

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The present study evaluates the possible drug interaction between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ) induced in diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction by molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg/kg, ip) and confirms it by assessing the blood and urine biochemical parameters on 28th day of its induction. Selected DN animals were used for the drug interaction between GLIM (0.5mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.) after 29th and 70th day of protocol. Drug interaction were assessed by evaluating the plasma drug concentration using HPLC-UV and also determine the change in the biochemical parameter in blood and urine. Mechanism of the interaction was postulated by molecular modeling study using Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in the blood and urine biochemical parameter in STZ treated groups. The concentration of SIL increased significantly (p<0.001) in rat plasma when co administered with GLIM after 70th day of protocol. Molecular modelling study revealed few important interactions with rat serum albumin and CYP2C9.GLIM has strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL. Whereas, for CYP2C9, GLIM has strong hydrogen bond with polar contacts and hydrophobic interactions than SIL. Present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals and mechanism has been supported by molecular modeling studies.

Keywords: diabetic nephropathy, glimepiride, sildenafil citrate, pharmacokinetics, homology modeling, schrodinger

Procedia PDF Downloads 361

Authors: Erfan Rahimi, Hadi Bahari Far, Mojgan Shikhpour

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Background: Urinary tract infection is one of the most common nosocomial infections, especially among women. E. coli is one of the main causes of urinary tract infections and one of the most common antibiotics to fight this bacterium is ampicillin. As conventional antibiotics led to bacterial antibiotic resistance, modification of the pure drugs can address this issue. The aim of this study was to prepare nanofluids containing carbon nanotubes conjugated with ampicillin to improve drug performance and reduce antibiotic resistance. Methods: Multi-walled carbon nanotubes (MWCNTs) were activated with thionyl chloride by reflux system and nanofluids containing antibiotics were prepared by ultrasonic method. The properties of the prepared nano-drug were investigated by general element analysis, infrared spectroscopy, Raman spectroscopy, scanning electron microscopy and transmission electron microscopy. After the treatment of the desired strain with nanofluid, microbial studies were performed to evaluate the antibacterial effects and molecular studies were carried out to measure the expression of the resistance gene AcrAB. Result: We have shown that the antimicrobial effect of ampicillin-functionalized MWCNTs at low concentrations performed better than that of the conventional drug in both resistant and ATCC strains. Also, a decrease in antibiotic resistance of bacteria treated with ampicillin-functionalized MWCNTs compared to the pure drug was observed. Also, ampicillin-functionalized MWCNTs downregulated the expression of AcrAB in treated bacteria. Conclusion: Because carbon nanotubes are capable of destroying the bacterial wall, which provides antibiotic resistance features in bacteria, their usage in the form of nanofluids can make lower dosages (about three times less) than that of the pure drug more effective. Additionally, the expression of the bacterial resistance gene AcrAB decreased, thereby reducing antibiotic resistance and improving drug performance against bacteria.

Keywords: urinary tract infection, antibiotic resistance, carbon nanotube, nanofluid

Procedia PDF Downloads 129

Authors: Anthony George Armiger II

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This paper focuses on the counternarcotic strategies of US government agencies in Afghanistan from 2001-2014. Despite a heavy US presence in the country, Afghanistan currently accounts for 80% of opium production worldwide and remains a key contributor to the global drug market. This paper argues that the divergent counternarcotic strategies of various US government agencies on the ground in Afghanistan are a product of the organizational differences amongst those agencies and that those differences can challenge the implementation of counternarcotics policies in Afghanistan. To gain a more in-depth perspective, this paper analyzes the counternarcotic strategies of two US government agencies in Afghanistan; the United States Department of Defense (DoD) and the Drug Enforcement Administration (DEA). Utilizing the framework of the organizational behavior model of organizational theory, this paper will highlight the varying organizational interests, opinions, standard operating procedures, and routines of both of the government agencies. The paper concludes with implications on counternarcotics, as well as the counterinsurgency in Afghanistan and provides recommendations for future research on foreign policy and counternarcotics.

Keywords: Afghanistan, drug policy, organizational theory, United States foreign policy

Procedia PDF Downloads 359

Authors: Mnasri Faiza, El Ganaoui Mohammed, Khelifa Mourad, Gabsi Slimane

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The main objective of this paper is to describe the hydrothermal behavior through porous material of construction due to temperature gradient. The construction proposed a bi-layer structure which composed of two different materials. The first is a bio-sourced panel named IBS-AKU (inertia system building), the second is the Neopor material. This system (IBS-AKU Neopor) is developed by a Belgium company (Isohabitat). The study suggests a multi-layer structure of the IBS-AKU panel in one dimension. A numerical method was proposed afterwards, by using the finite element method and a refined mesh area to strong gradients. The evolution of temperature fields and the moisture content has been processed.

Keywords: heat transfer, moisture diffusion, porous media, composite IBS-AKU, simulation

Procedia PDF Downloads 490

Authors: Nadjet Mekaouche, Hanane Zitouni, Fatma Boudia, Habiba Fetati, A. Saleh, A. Lardjam, H. Geniaux, A. Coubret, H. Toumi

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Medicines have undeniably played a major role in prolonging shelf life and improving quality. The absolute efficacy of the drug remains a lever for innovation, its benefit/risk balance is not always assured and it does not always have the expected effects. Prior to marketing, knowledge about adverse drug reactions is incomplete. Once on the market, phase IV drug studies begin. For years, the drug was prescribed with less care to a large number of very heterogeneous patients and often in combination with other drugs. It is at this point that previously unknown adverse effects may appear, hence the need for the implementation of a pharmacovigilance system. Pharmacovigilance represents all methods for detecting, evaluating, informing and preventing the risks of adverse drug reactions. The most severe adverse events occur frequently in hospital and that a significant proportion of adverse events result in hospitalizations. In addition, the consequences of hospital adverse events in terms of length of stay, mortality and costs are considerable. It, therefore, appears necessary to develop ‘hospital pharmacovigilance’ aimed at reducing the incidence of adverse reactions in hospitals. The most widely used monitoring method in pharmacovigilance is spontaneous notification. However, underreporting of adverse drug reactions is common in many countries and is a major obstacle to pharmacovigilance assessment. It is in this context that this study aims to describe the experience of the pharmacovigilance service at the University Hospital of Oran (EHUO). This is a retrospective study extending from 2011 to 2017, carried out on archived records of declarations collected at the level of the EHUO Pharmacovigilance Department. Reporting was collected by two methods: ‘spontaneous notification’ and ‘active pharmacovigilance’ targeting certain clinical services. We counted 217 statements. It involved 56% female patients and 46% male patients. Age ranged from 5 to 78 years with an average of 46 years. The most common adverse reaction was drug toxidermy. For the drugs in question, they were essentially according to the ATC classification of anti-infectives followed by anticancer drugs. As regards the evolution of declarations by year, a low rate of notification was noted in 2011. That is why we decided to set up an active approach at the level of some services where a resident of reference attended the staffs every week. This has resulted in an increase in the number of reports. The declarations came essentially from the services where the active approach was installed. This highlights the need for ongoing communication between all relevant health actors to stimulate reporting and secure drug treatments.

Keywords: adverse drug reactions, hospital, pharmacovigilance, spontaneous notification

Procedia PDF Downloads 152

Authors: Yuan-Chung Tsai, Masao Kamimura, Kohei Soga, Hsin-Cheng Chiu

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In order to enhance the photodynamic/photothermal therapeutic efficacy on glioblastoma, the functionized upconversion nanoparticles with the capability of converting the deep tissue penetrating near-infrared light into visible wavelength for activating photochemical reaction were developed. The drug-loaded nanoparticles (NPs) were obtained from the self-assembly of oleic acid-coated upconversion nanoparticles along with maleimide-conjugated poly(ethylene glycol)-cholesterol (Mal-PEG-Chol), as the NP stabilizer, and hydrophobic photosensitizers, IR-780 (for photothermal therapy, PTT) and mTHPC (for photodynamic therapy, PDT), in aqueous phase. Both the IR-780 and mTHPC were loaded into the hydrophobic domains within NPs via hydrophobic association. The peptide targeting ligand, angiopep-2, was further conjugated with the maleimide groups at the end of PEG adducts on the NP surfaces, enabling the affinity coupling with the low-density lipoprotein receptor-related protein-1 of tumor endothelial cells and malignant astrocytes. The drug-loaded NPs with the size of ca 80 nm in diameter exhibit a good colloidal stability in physiological conditions. The in vitro data demonstrate the successful targeting delivery of drug-loaded NPs toward the ALTS1C1 cells (murine astrocytoma cells) and the pronounced cytotoxicity elicited by combinational effect of PDT and PTT. The in vivo results show the promising brain orthotopic tumor targeting of drug-loaded NPs and sound efficacy for brain tumor dual-modality treatment. This work shows great potential for improving photodynamic/photothermal therapeutic efficacy of brain cancer.

Keywords: drug delivery, orthotopic brain tumor, photodynamic/photothermal therapies, upconversion nanoparticles

Procedia PDF Downloads 175

Authors: Shashank Tiwari

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The most common method of drug delivery is the oral solid dosage form, of which tablets and capsules are predominant. The tablet is more widely accepted and used compared to capsules for a number of reasons, such as cost/price, tamper resistance, ease of handling and packaging, ease of identification, and manufacturing efficiency. Over the past several years, the issue of tamper resistance has resulted in the conversion of most over-the-counter (OTC) drugs from capsules to predominantly all tablets.

Keywords: capsule, drug delivery, dosages, solid, tablet

Procedia PDF Downloads 418