Search results for: drug release kinetics
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3447

Search results for: drug release kinetics

2937 Prediction of Fire Growth of the Office by Real-Scale Fire Experiment

Authors: Kweon Oh-Sang, Kim Heung-Youl

Abstract:

Estimating the engineering properties of fires is important to be prepared for the complex and various fire risks of large-scale structures such as super-tall buildings, large stadiums, and multi-purpose structures. In this study, a mock-up of a compartment which was 2.4(L) x 3.6 (W) x 2.4 (H) meter in dimensions was fabricated at the 10MW LSC (Large Scale Calorimeter) and combustible office supplies were placed in the compartment for a real-scale fire test. Maximum heat release rate was 4.1 MW and total energy release obtained through the application of t2 fire growth rate was 6705.9 MJ.

Keywords: fire growth, fire experiment, t2 curve, large scale calorimeter

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2936 New Kinetic Approach to the Enzymatic Hydrolysis of Proteins: A Case of Thermolysin-Catalyzed Albumin

Authors: Anna Trusek-Holownia, Andrzej Noworyta

Abstract:

Using an enzyme of known specificity the hydrolysis of protein was carried out in a controlled manner. The aim was to obtain oligopeptides being the so-called active peptides or their direct precursors. An original way of expression of the protein hydrolysis kinetics was introduced. Peptide bonds contained in the protein were recognized as a diverse-quality substrate for hydrolysis by the applied protease. This assumption was positively verified taking as an example the hydrolysis of albumin by thermolysin. Peptide linkages for this system should be divided into at least four groups. One of them is a group of bonds non-hydrolyzable by this enzyme. These that are broken are hydrolyzed at a rate that differs even by tens of thousands of times. Designated kinetic constants were k'F = 10991.4 L/g.h, k'M = 14.83L/g.h, k'S about 10-1 L/g.h for fast, medium and slow bonds, respectively. Moreover, a procedure for unfolding of the protein, conducive to the improved susceptibility to enzymatic hydrolysis (approximately three-fold increase in the rate) was proposed.

Keywords: peptide bond hydrolysis, kinetics, enzyme specificity, biologically active peptides

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2935 Investigating Kinetics and Mathematical Modeling of Batch Clarification Process for Non-Centrifugal Sugar Production

Authors: Divya Vats, Sanjay Mahajani

Abstract:

The clarification of sugarcane juice plays a pivotal role in the production of non-centrifugal sugar (NCS), profoundly influencing the quality of the final NCS product. In this study, we have investigated the kinetics and mathematical modeling of the batch clarification process. The turbidity of the clarified cane juice (NTU) emerges as the determinant of the end product’s color. Moreover, this parameter underscores the significance of considering other variables as performance indicators for accessing the efficacy of the clarification process. Temperature-controlled experiments were meticulously conducted in a laboratory-scale batch mode. The primary objective was to discern the essential and optimized parameters crucial for augmenting the clarity of cane juice. Additionally, we explored the impact of pH and flocculant loading on the kinetics. Particle Image Velocimetry (PIV) is employed to comprehend the particle-particle and fluid-particle interaction. This technique facilitated a comprehensive understanding, paving the way for the subsequent multiphase computational fluid dynamics (CFD) simulations using the Eulerian-Lagrangian approach in the Ansys fluent. Impressively, these simulations accurately replicated comparable velocity profiles. The final mechanism of this study helps to make a mathematical model and presents a valuable framework for transitioning from the traditional batch process to a continuous process. The ultimate aim is to attain heightened productivity and unwavering consistency in product quality.

Keywords: non-centrifugal sugar, particle image velocimetry, computational fluid dynamics, mathematical modeling, turbidity

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2934 Graphene-Based Nanocomposites as Ecofriendly Antifouling Surfaces

Authors: Mohamed S. Selim, Nesreen A. Fatthallah, Shimaa A. Higazy, Zhifeng Hao, Xiang Chen

Abstract:

After the prohibition of tin-based fouling-prevention coatings in 2003, the researchers were directed toward eco-friendly coatings. Because of their nonstick, environmental, and economic benefits, foul-release nanocoatings have received a lot of attention. They use physical anti-adhesion terminology to deter any fouling attachment.Natural bioinspired surfaces have micro/nano-roughness and low surface free energy features, which may inspire the design of dynamic antifouling coatings. Graphene-based nanocomposite surfaces were designed to combat marine-fouling adhesion with ecological as well as eco-friendly effects rather than biocidal solutions. Polymer–graphenenanofiller hybrids are a novel class of composite materials in fouling-prevention applications. The controlled preparation of nanoscale orientation, arrangement, and direction along the composite building blocks would result in superior fouling prohibition. This work representsfoul-release nanocomposite top coats for marine coating applications with superhydrophobicity, surface inertness against fouling adherence, cost-effectiveness, and increased lifetime.

Keywords: foul-release nanocoatings, graphene-based nanocomposite, polymer, nanofillers

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2933 In situ Growth of ZIF-8 on TEMPO-Oxidized Cellulose Nanofibril Film and Coated with Pectin for pH and Enzyme Dual-Responsive Controlled Release Active Packaging

Authors: Tiantian Min, Chuanxiang Cheng, Jin Yue

Abstract:

The growth and reproduction of microorganisms in food packaging can cause food decay and foodborne diseases, which pose a serious threat to the health of consumers and even cause serious economic losses. Active food packaging containing antibacterial bioactive compounds is a promising strategy for extending the shelf life of products and maintaining the food quality, as well as reducing the food waste. However, most active packaging can only act as slow-release effect for antimicrobials, which causes the release rate of antimicrobials not match the growth rate of microorganisms. Stimuli-responsive active packaging materials based on biopolymeric substrates and bioactive substances that respond to some biological and non-biological trigger factors provide more opportunities for fresh food preservation. The biological stimuli factors such as relative humidity, pH and enzyme existed in the exudate secreted by microorganisms have been expected to design food packaging materials. These stimuli-responsive materials achieved accurate release or delivery of bioactive substances at specific time and appropriate dose. Recently, metal-organic-frameworks (MOFs) nanoparticles become attractive carriers to enhance the efficiency of bioactive compounds or drugs. Cellulose nanofibrils have been widely applied for film substrates due to their biodegradability and biocompatibility. The abundant hydroxyl groups in cellulose can be oxidized to carboxyl groups by TEMPO, making it easier to anchoring MOFs and to be further modification. In this study, a pH and enzyme dual-responsive CAR@ZIF-8/TOCNF/PE film was fabricated by in-situ growth of ZIF-8 nanoparticles onto TEMPO-oxidized cellulose (TOCNF) film and further coated with pectin (PE) for stabilization and controlled release of carvacrol (CAR). The enzyme triggered release of CAR was achieved owing to the degradation of pectin by pectinase secreted by microorganisms. Similarly, the pH-responsive release of CAR was attributed to the unique skeleton degradation of ZIF-8, further accelerating the release of CAR from the topological structure of ZIF-8. The composite film performed excellent crystallinity and adsorb ability confirmed by X-ray diffraction and BET analysis, and the inhibition efficiency against Escherichia coli, Staphylococcus aureus and Aspergillus niger reached more than 99%. The composite film was capable of releasing CAR when exposure to dose-dependent enzyme (0.1, 0.2, and 0.3 mg/mL) and acidic condition (pH = 5). When inoculated 10 μL of Aspergillus niger spore suspension on the equatorial position of mango and raspberries, this composite film acted as packaging pads effectively inhibited the mycelial growth and prolonged the shelf life of mango and raspberries to 7 days. Such MOF-TOCNF based film provided a targeted, controlled and sustained release of bioactive compounds for long-term antibacterial activity and preservation effect, which can also avoid the cross-contamination of fruits.

Keywords: active food packaging, controlled release, fruit preservation, in-situ growth, stimuli-responsive

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2932 There Is No Meaningful Opportunity in Meaningless Data: Why It Is Unconstitutional to Use Life Expectancy Tables in Post-Graham Sentences

Authors: Stacie Nelson Colling, Adele Cummings

Abstract:

The United States Supreme Court recently announced that it is unconstitutional to sentence a child to life without parole for non-homicide offenses, and that each child so situated must be afforded a meaningful opportunity for release from prison in his lifetime. The Court also declared that it is unconstitutional to impose a mandatory sentence of life without parole on a child for homicide offenses. Across the United States, attorneys and advocates continue to litigate issues surrounding the implementation of these legal principles. Some states have held that any sentence to a finite term of years, no matter how long, is not the same as ‘life’ and therefore does not violate the constitution. Other states have held that a sentence to a term of years that is less than the expected life of that particular child is not unconstitutional. In Colorado, the courts have routinely looked to life expectancy estimates from governmental organizations to determine how long a particular child is expected to live. They then compare that the date that the child is expected to be eligible for parole, and if the child is expected to still be living when he is eligible for parole, the sentence is deemed constitutional. This paper argues that it is inappropriate, reckless, unconstitutional and not scientifically sound to use such estimates in determining whether a child will have a meaningful opportunity for release from prison and life outside of prison before he dies. This paper argues that the opportunity for release must mean more than a probability that a child will be released before his death, and that it must include an opportunity for a meaningful life outside of prison (not just the opportunity to be released and then die on the outside). The paper further argues that life expectancy estimates cannot guide a court or a legislature in determining whether a sentence is or is not constitutional.

Keywords: life without parole, life expectancy, juvenile sentencing, meaningful opportunity for release from prison

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2931 Simulation of Cure Kinetics and Process-Induced Stresses in Carbon Fibre Composite Laminate Manufactured by a Liquid Composite Molding Technique

Authors: Jayaraman Muniyappan, Bachchan Kr Mishra, Gautam Salkar, Swetha Manian Sridhar

Abstract:

Vacuum Assisted Resin Transfer Molding (VARTM), a cost effective method of Liquid Composite Molding (LCM), is a single step process where the resin, at atmospheric pressure, is infused through a preform that is maintained under vacuum. This hydrodynamic pressure gradient is responsible for the flow of resin through the dry fabric preform. The current study has a slight variation to traditional VARTM, wherein, the resin infuses through the fabric placed on a heated mold to reduce its viscosity. The saturated preform is subjected to a cure cycle where the resin hardens as it undergoes curing. During this cycle, an uneven temperature distribution through the thickness of the composite and excess exothermic heat released due to different cure rates result in non-uniform curing. Additionally, there is a difference in thermal expansion coefficient between fiber and resin in a given plane and between adjacent plies. All these effects coupled with orthotropic coefficient of thermal expansion of the composite give rise to process-induced stresses in the laminate. Such stresses lead to part deformation when the laminate tries to relieve them as the part is released off the mold. The current study looks at simulating resin infusion, cure kinetics and the structural response of composite laminate subject to process-induced stresses.

Keywords: cure kinetics, process-induced stresses, thermal expansion coefficient, vacuum assisted resin transfer molding

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2930 Stability-Indicating High-Performance Thin-Layer Chromatography Method for Estimation of Naftopidil

Authors: P. S. Jain, K. D. Bobade, S. J. Surana

Abstract:

A simple, selective, precise and Stability-indicating High-performance thin-layer chromatographic method for analysis of Naftopidil both in a bulk and in pharmaceutical formulation has been developed and validated. The method employed, HPTLC aluminium plates precoated with silica gel as the stationary phase. The solvent system consisted of hexane: ethyl acetate: glacial acetic acid (4:4:2 v/v). The system was found to give compact spot for Naftopidil (Rf value of 0.43±0.02). Densitometric analysis of Naftopidil was carried out in the absorbance mode at 253 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r2=0.999±0.0001 with respect to peak area in the concentration range 200-1200 ng per spot. The method was validated for precision, recovery and robustness. The limits of detection and quantification were 20.35 and 61.68 ng per spot, respectively. Naftopidil was subjected to acid and alkali hydrolysis, oxidation and thermal degradation. The drug undergoes degradation under acidic, basic, oxidation and thermal conditions. This indicates that the drug is susceptible to acid, base, oxidation and thermal conditions. The degraded product was well resolved from the pure drug with significantly different Rf value. Statistical analysis proves that the method is repeatable, selective and accurate for the estimation of investigated drug. The proposed developed HPTLC method can be applied for identification and quantitative determination of Naftopidil in bulk drug and pharmaceutical formulation.

Keywords: naftopidil, HPTLC, validation, stability, degradation

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2929 Synthesis of Graphene Oxide/Chitosan Nanocomposite for Methylene Blue Adsorption

Authors: S. Melvin Samuel, Jayanta Bhattacharya

Abstract:

In the present study, a graphene oxide/chitosan (GO-CS) composite material was prepared and used as an adsorbent for the removal of methylene blue (MB) from aqueous solution. The synthesized GO-CS adsorbent was characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopes (SEM), transmission electron microscopy (TEM), Raman spectroscopy and thermogravimetric analysis (TGA). The removal of MB was conducted in batch mode. The effect of parameters influencing the adsorption of MB such as pH of the solution, initial MB concentration, shaking speed, contact time and adsorbent dosage were studied. The results showed that the GO-CS composite material has high adsorption capacity of 196 mg/g of MB solution at pH 9.0. Further, the adsorption of MB on GO-CS followed pseudo second order kinetics and equilibrium adsorption data well fitted by the Langmuir isotherm model. The study suggests that the GO-CS is a favorable adsorbent for the removal of MB from aqueous solution.

Keywords: Methylene blue, Graphene oxide-chitosan, Isotherms, Kinetics.

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2928 The Effect of the Combination of Methotrexate Nanoparticles and TiO2 on Breast Cancer

Authors: Nusaiba Al-Nemrawi, Belal Al-Husein

Abstract:

Methotrexate (MTX) is a stoichiometric inhibitor of dihydrofolate reductase, which is essential for DNA synthesis. MTX is a chemotherapeutic agent used for treating many types of cancer cells. However, cells’ resistant to MTX is very common and its pharmacokinetic behavior is highly problematic. of MTX within tumor cells, we propose encapsulation of antitumor drugs in nanoparticulated systems. Chitosan (CS) is a naturally occurring polymer that is biocompatibe, biodegradable, non-toxic, cationic and bioadhesive. CS nanoparticles (CS-NPs) have been used as drug carrier for targeted delivery. Titanium dioxide (TiO2), a natural mineral oxide, which is used in biomaterials due to its high stability and antimicrobial and anticorrosive properties. TiO2 showed a potential as a tumor suppressor. In this study a new formulation of MTX loaded in CS NPs (CS-MTX NPs) and coated with Titanium oxide (TiO2) was prepared. The mean particle size, zeta potential, polydispersity index were measured. The interaction between CS NPs and TiO2 NPs was confirmed using FTIR and XRD. CS-MTX NPs was studied in vitro using the tumor cell line MCF-7 (human breast cancer). The results showed that CS-MTX has a size around 169 nm and as they were coated with TiO2, the size ranged between and depending on the ratio of CS-MTX to TiO2 ratio used in the preparation. All NPs (uncoated and coated carried positive charges and were monodispersed. The entrapment efficacy was around 65%. Both FTIR and XRD proved that TiO2 interacted with CS-MTX NPs. The drug invitro release was controlled and sustained over days. Finally, the studied in vitro using the tumor cell line MCF-7 suggested that combining nanomaterials with anticancer drugs CS-MTX NPs may be more effective than free MTX for cancer treatment. In conclusion, the combination of CS-MTX NPs and TiO2 NPs showed excellent time-dependent in vitro antitumor behavior, therefore, can be employed as a promising anticancer agent to attain efficient results towards MCF-7 cells.

Keywords: Methotrexate, Titanium dioxide, Chitosan nanoparticles, cancer

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2927 Prevalence and Pattern of Drug Usage among Youth in Ogbomoso, Nigeria

Authors: Samson F. Agberotimi, Rachel B. Asagba, Choja Oduaran

Abstract:

Disturbing rate of use of different substances such as cannabis, alcohol, as well as pharmaceutical drugs among Nigerian youth in recent times has been affirmed in the literature. There is, however, a paucity of literature addressing the pattern of usage of such drugs, especially for clinical relevance and intervention planning. The present study investigated the prevalence and pattern of drug usage among youth in Ogbomoso, Nigeria. A cross-sectional survey involving 92 purposively selected participants comprising of 82 males and 10 females aged between 15 and 24 years was conducted. A measure of drug involvement and demographic characteristics was administered to the participants. Descriptive analysis was done using the SPSS v.21. Cannabis (79.4%), alcohol (77.2%), codeine (70.7%), tobacco (65.2%) and tramadol (47.8%) are the five most frequently used substances. However, the majority of the users of tobacco (68.3%) and alcohol (62.0%) are casual users indicating a mild level of use of the substances among the participants. On the other hand, 49.2% of the codeine users, 27.3% of the tramadol users, and 21.9% of the cannabis users reported harmful/intensive levels of use. Furthermore, the results revealed individuals at the pathological level of use as 28.8% for cannabis, 25.0% for tramadol, and 21.6% for codeine, and thus require clinical/therapeutic intervention. In conclusion, cannabis remains the most frequently used substance among youths. However, there appears to be a shift from the use of conventional psychoactive substances to pharmaceutical/prescription drugs such as codeine and tramadol. The findings of this study raised the need for both preventive and therapeutic interventions addressing the problem of substance use disorder among youth in contemporary society.

Keywords: Ogbomoso, pattern of drug use, prevalence of drug use, youth

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2926 Acid-Responsive Polymer Conjugates as a New Generation of Corrosion Protecting Materials

Authors: Naruphorn Dararatana, Farzad Seidi, Daniel Crespy

Abstract:

Protection of metals is a critical issue in industry. The annual cost of corrosion in the world is estimated to be about 2.5 trillion dollars and continuously increases. Therefore, there is a need for developing novel protection approaches to improve corrosion protection. We designed and synthesized smart polymer/corrosion inhibitor conjugates as new generations of corrosion protecting materials. Firstly, a polymerizable acrylate derivative of 8-hydroxyquinoline (8HQ), an effective corrosion inhibitor, containing acid-labile β-thiopropionate linkage was prepared in three steps. Then, it was copolymerized with ethyl acrylate in the presence of 1,1′-azobis(cyclohexanecarbonitrile) (ABCN) by radical polymerization. Nanoparticles with an average diameter of 140 nm were prepared from the polymer conjugate by the miniemulsion-solvent evaporation process. The release behavior of 8HQ from the the nanoparticles was studied in acidic (pH 3.5) and neutral media (pH 7.0). The release profile showed a faster release of 8HQ in acidic medium in comparison with neutral medium. Indeed 100% of 8HQ was released after 14 days in acidic medium whereas only around 15% of 8HQ was released during the same period at neutral pH. Therefore, the polymer conjugate nanoparticles are suitable materials as additives or to form coatings on metal substrates for corrosion protection.

Keywords: Corrosion inhibitor, 8-Hydroxyquinoline, Polymer conjugated, β-Thiopropionate

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2925 Drying Kinetics of Okara (Soy Pulp) Using the Multi-Commodity Heat Pump Dryer (MCHPD)

Authors: Lorcelie B. Taclan, Jolly S. Balila, Maribel Balagtas, Eunice M. Aclan, Myrtle C. Orbon, Emson Y. Taclan, Irenea A. Centeno

Abstract:

Okara (soy pulp), a by-product and waste from the production of soymilk, tufo and tokwa and soybean-based vegan food products is readily available in the university thrice a week. The Food Factory owned and managed by AUP produces these food products weekly. Generally the study was conducted to determine the drying kinetics of soya pulp using the MCHPD. Specifically, it aimed to establish the time of drying; moisture loss per hour and percent moisture content of soya pulp and to establish the dried okara as an ingredient to other foods. The MCHPD is drying equipment that has an ideal drying condition of 50.00C and 10.0% relative humidity. Fresh and wet soya pulp were weighed at 1.0 kg per tray (21 drying trays), laid on the trays lined with cheese cloth. The MCHPD was set to desired drying conditions. Weight loss was monitored every hour and calculated using standard formulas. Research results indicated that the drying time for soya pulp was 19.0 hours; the % moisture content was reduced from 87.6.0% to 9.7.0% at an average moisture loss of 3.0 g/hr. The nutritional values of okara were favorably maintained with enhanced color. The dried okara was added as an ingredient to other healthy bakery products produced by the AUP Food Factory. Making use of okara would add nutritional values to other food products and would also help waste management concerns inside the university.

Keywords: okara, MCHPD, drying kinetics, nutritional values, waste management

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2924 Kinetics Analysis of Lignocellulose Hydrolysis and Glucose Consumption Using Aspergillus niger in Solid State

Authors: Akida Mulyaningtyas, Wahyudi Budi Sediawan

Abstract:

One decisive stage in bioethanol production from plant biomass is the hydrolysis of lignocellulosic materials into simple sugars such as glucose. The produced glucose is then fermented into ethanol. This stage is popularly done in biological method by using cellulase that is produced by certain fungi. As it is known, glucose is the main source of nutrition for most microorganisms. Therefore, cutting cellulose into glucose is actually an attempt of microorganism to provide nutrition for itself. So far, this phenomenon has received less attention while it is necessary to identify the quantity of sugar consumed by the microorganism. In this study, we examined the phenomenon of sugar consumption by microorganism on lignocellulosic hydrolysis. We used oil palm empty fruit bunch (OPEFB) as the source of lignocellulose and Aspergillus niger as cellulase-producing fungus. In Indonesia, OPEFB is plantation waste that is difficult to decompose in nature and causes environmental problems. First, OPEFB was pretreated with 1% of NaOH at 170 oC to destroy lignin that hindered A.niger from accessing cellulose. The hydrolysis was performed by growing A.niger on pretreated OPEFB in solid state to minimize the possibility of contamination. The produced glucose was measured every 24 hours for 9 days. We analyzed the kinetics of both reactions, i.e., hydrolysis and glucose consumption, simultaneously. The constants for both reactions were assumed to follow the Monod equation. The results showed that the reaction constant of glucose consumption (μC) was higher than of cellulose hydrolysis (μH), i.e., 11.8 g/L and 0.62 g/L for glucose consumption and hydrolysis respectively. However, in general, the reaction rate of hydrolysis is greater than of glucose consumption since the cellulose concentration as substrate in hydrolysis is much higher than glucose as substrate in the consumption reaction.

Keywords: Aspergillus niger, bioethanol, hydrolysis, kinetics

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2923 Control of IL-23 Release in Dendritic Cells Protects Mice from Imiquimod-Induced Psoriasis

Authors: Xingxin Wu, Fenli Shao, Tao Tan, Yang Tan, Yang Sun, Qiang Xu

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Psoriasis is a chronic inflammatory skin disease that affects about 2% of the world's population. IL-23 signaling plays a key role in the pathogenesis of psoriasis. Control of IL-23 release by small molecule compounds during developing psoriasis has not been well established. Here, we show that compound 1, a small molecule nature product, protected mice from imiquimod-induced psoriasis with improved skin lesions, reduced skin thickness, and reduced IL-23 mRNA expression in the skin tissue. FACS results showed compound 1 reduced the number of dendritic cells in the skin. Interestingly, compound 1 was not able to ameliorate IL-23-induced psoriasis-like skin inflammation in mice. Further, compound 1 inhibited MyD88-dependent IL-23 mRNA expression induced by LPS, CpG and imiquimod in BMDC cells, but not MyD88-independent CD80 and CD86 expression induced by LPS. The methods included real-time PCR, western blot, H & E staining, FACS and ELISA et al. In conclusion, compound 1 regulates MyD88-dependent signaling to control IL-23 release in dendritic cells, which improves imiquimod-induced psoriasis.

Keywords: dendritic cells, IL-23, toll-like receptor signaling, psoriasis

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2922 The Improvement of Disease-Modifying Osteoarthritis Drugs Model Uptake and Retention within Two Cartilage Models

Authors: Polina Prokopovich

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Disease-modifying osteoarthritis drugs (DMOADs) are a new therapeutic class for OA, preventing or inhibiting OA development. Unfortunately, none of the DMOADs have been clinically approved due to their poor therapeutic effects in clinical trials. The joint environment has played a role in the poor clinical performance of these drugs by limiting the amount of drug effectively delivered as well as the time that the drug spends within the joint space. The current study aims to enhance the cartilage uptake and retention time of the DMOADs-model (licofelone), which showed a significant therapeutic effect against OA progression and is currently in phase III. Licofelone will be covalently conjugated to the hydrolysable, cytocompatible, and cationic poly beta-amino ester polymers (PBAE). The cationic polymers (A16 and A87) can be electrostatically attached to the negatively charged cartilage component (glycosaminoglycan), which will increase the drug penetration through the cartilage and extend the drug time within the cartilage. In the cartilage uptake and retention time studies, an increase of 18 to 37 times of the total conjugated licofelone to A87 and A16 was observed when compared to the free licofelone. Furthermore, the conjugated licofelone to A87 was detectable within the cartilage at 120 minutes, while the free licofelone was not detectable after 60 minutes. Additionally, the A87-licofelone conjugate showed no effect on the chondrocyte viability. In conclusion, the cationic A87 and A16 polymers increased the percentage of licofelone within the cartilage, which could potentially enhance the therapeutic effect and pharmacokinetic performance of licofelone or other DMOADs clinically.

Keywords: PBAE, cartilage., osteoarthritis, injectable biomaterials, drug delivery

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2921 Brewing in a Domestic Refrigerator Using Freeze-Dried Raw Materials

Authors: Angelika-Ioanna Gialleli, Gousi Mantha, Maria Kanellaki, Bekatorou Argyro, Athanasios Koutinas

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In this study, a new brewing technology with dry raw materials is proposed with potential application in home brewing. Bio catalysts were prepared by immobilization of the psychrotolerant yeast strain Saccharomyces cerevisiae AXAZ-1 on tubular cellulose. Both the word and the biocatalysts were freeze-dried without any cryoprotectants and used for low temperature brewing. The combination of immobilization and freeze-drying techniques was applied successfully, giving a potential for supplying breweries with preserved and ready-to-use immobilized cells. The effect of wort sugar concentration (7°, 8.5°, 10°Be), temperature (2, 5, 7° C) and carrier concentration (5, 10, 20 g/L) on fermentation kinetics and final product quality (volatiles, colour, polyphenols, bitterness) was assessed. The same procedure was repeated with free cells for comparison of the results. The results for immobilized cells were better compared to free cells regarding fermentation kinetics and organoleptic characteristics.

Keywords: brewing, tubular cellulose, low temperature, biocatalyst

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2920 Development and Obtaining of Solid Dispersions to Increase the Solubility of Efavirenz in Anti-HIV Therapy

Authors: Salvana P. M. Costa, Tarcyla A. Gomes, Giovanna C. R. M. Schver, Leslie R. M. Ferraz, Cristovão R. Silva, Magaly A. M. Lyra, Danilo A. F. Fonte, Larissa A. Rolim, Amanda C. Q. M. Vieira, Miracy M. Albuquerque, Pedro J. Rolim-neto

Abstract:

Efavirenz (EFV) is considered one of the most widely used anti-HIV drugs. However, it is classified as a drug class II (poorly soluble, highly permeable) according to the biopharmaceutical classification system, presenting problems of absorption in the gastrointestinal tract and thereby inadequate bioavailability for its therapeutic action. This study aimed to overcome these barriers by developing and obtaining solid dispersions (SD) in order to increase the EFZ bioavailability. For the development of SD with EFV, theoretical and practical studies were initially performed. Thus, there was a choice of a carrier to be used. For this, it was analyzed the various criteria such as glass transition temperature of the polymer, intra- and intermolecular interactions of hydrogen bonds between drug and polymer, the miscibility between the polymer and EFV. The choice of the obtainment method of the SD came from the analysis of which method is the most consolidated in both industry and literature. Subsequently, the choice of drug and carrier concentrations in the dispersions was carried out. In order to obtain DS to present the drug in its amorphous form, as the DS were obtained, they were analyzed by X-ray diffraction (XRD). SD are more stable the higher the amount of polymer present in the formulation. With this assumption, a SD containing 10% of drug was initially prepared and then this proportion was increased until the XRD showed the presence of EFV in its crystalline form. From this point, it was not produced SD with a higher concentration of drug. Thus, it was allowed to select PVP-K30, PVPVA 64 and the SOLUPLUS formulation as carriers, once it was possible the formation of hydrogen bond between EFV and polymers since these have hydrogen acceptor groups capable of interacting with the donor group of the drug hydrogen. It is worth mentioning also that the films obtained, independent of concentration used, were presented homogeneous and transparent. Thus, it can be said that the EFV is miscible in the three polymers used in the study. The SD and Physical Mixtures (PM) with these polymers were prepared by the solvent method. The EFV diffraction profile showed main peaks at around 2θ of 6,24°, in addition to other minor peaks at 14,34°, 17,08°, 20,3°, 21,36° and 25,06°, evidencing its crystalline character. Furthermore, the polymers showed amorphous nature, as evidenced by the absence of peaks in their XRD patterns. The XRD patterns showed the PM overlapping profile of the drug with the polymer, indicating the presence of EFV in its crystalline form. Regardless the proportion of drug used in SD, all the samples showed the same characteristics with no diffraction peaks EFV, demonstrating the behavior amorphous products. Thus, the polymers enabled, effectively, the formation of amorphous SD, probably due to the potential hydrogen bonds between them and the drug. Moreover, the XRD analysis showed that the polymers were able to maintain its amorphous form in a concentration of up to 80% drug.

Keywords: amorphous form, Efavirenz, solid dispersions, solubility

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2919 Understanding the Dynamics of Linker Histone Using Mathematical Modeling and FRAP Experiments

Authors: G. Carrero, C. Contreras, M. J. Hendzel

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Linker histones or histones H1 are highly mobile nuclear proteins that regulate the organization of chromatin and limit DNA accessibility by binding to the chromatin structure (DNA and associated proteins). It is known that this binding process is driven by both slow (strong binding) and rapid (weak binding) interactions. However, the exact binding mechanism has not been fully described. Moreover, the existing models only account for one type of bound population that does not distinguish explicitly between the weakly and strongly bound proteins. Thus, we propose different systems of reaction-diffusion equations to describe explicitly the rapid and slow interactions during a FRAP (Fluorescence Recovery After Photobleaching) experiment. We perform a model comparison analysis to characterize the binding mechanism of histone H1 and provide new meaningful biophysical information on the kinetics of histone H1.

Keywords: FRAP (Fluorescence Recovery After Photobleaching), histone H1, histone H1 binding kinetics, linker histone, reaction-diffusion equation

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2918 Kinetic and Thermodynamics of Sorption of 5-Fluorouracil (5-Fl) on Carbon Nanotubes

Authors: Muhammad Imran Din

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The aim of this study was to understand the interaction between multi-walled carbon nano tubes (MCNTs) and anticancer agents and evaluate the drug-loading ability of MCNTs. Batch adsorption experiments were carried out for adsorption of 5-Fluorouracil (5-FL) using MCNTs. The effect of various operating variables, viz., adsorbent dosage, pH, contact time and temperature for adsorption of 5-Fluorouracil (5-FL) has been studied. The Freundlich adsorption model was successfully employed to describe the adsorption process. It was found that the pseudo-second-order mechanism is predominant and the overall rate of the 5-Fluorouracil (5-FL) adsorption process appears to be controlled by the more than one-step. Thermodynamic parameters such as free energy change (ΔG°), enthalpy change (ΔH°) and entropy change (ΔS°) have been calculated respectively, revealed the spontaneous, endothermic and feasible nature of adsorption process. The results showed that carbon nano tubes were able to form supra molecular complexes with 5-Fluorouracil (5-FL) by π-π stacking and possessed favorable loading properties as drug carriers.

Keywords: drug, adsorption, anticancer, 5-Fluorouracil (5-FL)

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2917 Mode of Action of Surface Bound Antimicrobial Peptides Melimine and Mel4 against Pseudomonas aeruginosa

Authors: Muhammad Yasir, Debarun Dutta, Mark Willcox

Abstract:

Biomaterial-associated infections are a multi-billion dollar burden globally. Antimicrobial peptide-based coatings may be able to prevent such infections. The aim of this study was to investigate the mechanism of action surface bound peptides (AMPs) against Pseudomonas aeruginosa 6294. Melimine and Mel4 were covalently attached to glass coverslips using azido-benzoic acid. Attachment was confirmed using X-ray photoelectron spectroscopy. P. aeruginosa was allowed to attach to AMP-coated glass for up to 6 hours. The effect of the surface-bound AMPs on bacterial cell membranes was evaluated using the dyes DiSC3-(5), Sytox green, SYTO 9 and propidium iodide with fluorescence microscopy. Release of cytoplasmic materials ATP and DNA/RNA were determined in the surrounding fluid. The amount of cell death was estimated by agar plate counts. The AMPs were successfully covalently bound to the glass as demonstrated by increases in %nitrogen of 3.6% (melimine) and 2.3% (Mel4) compared to controls. Immobilized peptides disrupted the cytoplasmic membrane potential of P. aeruginosa within 10 min. This was followed by the release of ATP after 2 h. Membrane permeabilization started at 3 h of contact with glass coated AMPs. There was a significant number of bacteria (59% for melimine; 36% for Mel-4) with damaged membranes after 4 h of contact. At the 6 h time point, release of DNA occurred with melimine releasing 2 times the amount of DNA/RNA than Mel4 surfaces (p < 0.05). Surface bound AMPs were able to disrupt cell membranes with subsequent release of cytoplasmic materials, and ultimately resulting in bacterial death.

Keywords: biomaterials, immobilized antimicrobial peptides, P. aeruginosa, mode of action

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2916 Suppression of DMBA/TPA-Induced Skin Tumorigenesis by Menthol through Inhibition of Inflammation, NF-kappaB, Ras-Raf-ERK Pathway

Authors: Zhaoguo Liu, Cunsi Shen, Yin Lu

Abstract:

Growing evidence has shown that menthol has potent anticancer activity in various human cancers. However, its effect on skin cancer remains largely unknown. In the present study, we investigated the chemopreventive potential of menthol against 7, 12-dimethylbenz[a] anthracene(DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA)-induced skin tumorigenesis in ICR mice. Our results showed that menthol significantly inhibited TPA-induced inflammatory responses and pro-inflammatory cytokine release. We also found that menthol treatment significantly inhibited TPA-induced lipid peroxidation (LPO), mouse UDP-glucumno-syltransferase (UGT), mouse NADH Dehydrogenase, Quinone 1 (NQO1) release. Furthermore, we found menthol treatment significantly inhibited the tumor incidence and number of tumors (P < 0.001). Interestingly, we observed that menthol treatment significantly inhibited TPA-induced altered activity of NF-κB in skin tumor. Consistently, menthol-treated tumors also showed significantly suppressed the Ras-Raf-ERK signaling pathway. Thus, our results suggest that menthol inhibits DMBA/TPA-induced skin tumorigenesis by attenuating the Ras and inhibiting NF-κB activity via inhibition of inflammation responses and pro-inflammatory cytokine release.

Keywords: DMBA/TPA, NF-κB, Ras-Raf-ERK, skin tumorigenesis

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2915 Time to Second Line Treatment Initiation Among Drug-Resistant Tuberculosis Patients in Nepal

Authors: Shraddha Acharya, Sharad Kumar Sharma, Ratna Bhattarai, Bhagwan Maharjan, Deepak Dahal, Serpahine Kaminsa

Abstract:

Background: Drug-resistant (DR) tuberculosis (TB) continues to be a threat in Nepal, with an estimated 2800 new cases every year. The treatment of DR-TB with second line TB drugs is complex and takes longer time with comparatively lower treatment success rate than drug-susceptible TB. Delay in treatment initiation for DR-TB patients might further result in unfavorable treatment outcomes and increased transmission. This study thus aims to determine median time taken to initiate second-line treatment among Rifampicin Resistant (RR) diagnosed TB patients and to assess the proportion of treatment delays among various type of DR-TB cases. Method: A retrospective cohort study was done using national routine electronic data (DRTB and TB Laboratory Patient Tracking System-DHIS2) on drug resistant tuberculosis patients between January 2020 and December 2022. The time taken for treatment initiation was computed as– days from first diagnosis as RR TB through Xpert MTB/Rif test to enrollment on second-line treatment. The treatment delay (>7 days after diagnosis) was calculated. Results: Among total RR TB cases (N=954) diagnosed via Xpert nationwide, 61.4% were enrolled under shorter-treatment regimen (STR), 33.0% under longer treatment regimen (LTR), 5.1% for Pre-extensively drug resistant TB (Pre-XDR) and 0.4% for Extensively drug resistant TB (XDR) treatment. Among these cases, it was found that the median time from diagnosis to treatment initiation was 6 days (IQR:2-15.8). The median time was 5 days (IQR:2.0-13.3) among STR, 6 days (IQR:3.0-15.0) among LTR, 30 days (IQR:5.5-66.8) among Pre-XDR and 4 days (IQR:2.5-9.0) among XDR TB cases. The overall treatment delay (>7 days after diagnosis) was observed in 42.4% of the patients, among which, cases enrolled under Pre-XDR contributed substantially to treatment delay (72.0%), followed by LTR (43.6%), STR (39.1%) and XDR (33.3%). Conclusion: Timely diagnosis and prompt treatment initiation remain fundamental focus of the National TB program. The findings of the study, however suggest gaps in timeliness of treatment initiation for the drug-resistant TB patients, which could bring adverse treatment outcomes. Moreover, there is an alarming delay in second line treatment initiation for the Pre-XDR TB patients. Therefore, this study generates evidence to identify existing gaps in treatment initiation and highlights need for formulating specific policies and intervention in creating effective linkage between the RR TB diagnosis and enrollment on second line TB treatment with intensified efforts from health providers for follow-ups and expansion of more decentralized, adequate, and accessible diagnostic and treatment services for DR-TB, especially Pre-XDR TB cases, due to the observed long treatment delays.

Keywords: drug-resistant, tuberculosis, treatment initiation, Nepal, treatment delay

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2914 Effect of Dissolved Oxygen Concentration on Iron Dissolution by Liquid Sodium

Authors: Sami Meddeb, M. L Giorgi, J. L. Courouau

Abstract:

This work presents the progress of studies aiming to guarantee the lifetime of 316L(N) steel in a sodium-cooled fast reactor by determining the elementary corrosion mechanism, which is akin to an accelerated dissolution by dissolved oxygen. The mechanism involving iron, the main element of steel, is particularly studied in detail, from the viewpoint of the data available in the literature, the modeling of the various mechanisms hypothesized. Experiments performed in the CORRONa facility at controlled temperature and dissolved oxygen content are used to test both literature data and hypotheses. Current tests, performed at various temperatures and oxygen content, focus on specifying the chemical reaction at play, determining its free enthalpy, as well as kinetics rate constants. Specific test configuration allows measuring the reaction kinetics and the chemical equilibrium state in the same test. In the current state of progress of these tests, the dissolution of iron accelerated by dissolved oxygen appears as directly related to a chemical complexation reaction of mixed iron-sodium oxide (Na-Fe-O), a compound that is soluble in the liquid sodium solution. Results obtained demonstrate the presence in the solution of this corrosion product, whose kinetics is the limiting step under the conditions of the test. This compound, the object of hypotheses dating back more than 50 years, is predominant in solution compared to atomic iron, presumably even for the low oxygen concentration, and cannot be neglected for the long-term corrosion modeling of any heat transfer system.

Keywords: corrosion, sodium fast reactors, iron, oxygen

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2913 Investigation of Chronic Drug Use Due to Chronic Diseases in Patients Admitted to Emergency Department

Authors: Behcet Al, Şener Cindoruk, Suat Zengin, Mehmet Murat Oktay, Mehmet Mustafa Sunar, Hatice Eroglu, Cuma Yildirim

Abstract:

Objective: In present study we aimed to investigate the chronic drug use due to chronic diseases in patients admitted to emergency department. Materials-Methods: 144 patients who applied to emergency department (ED) of medicine school of Gaziantep University between June 2013 and September 2013 with chronic diseases and use chronic drugs were included. Information about drugs used by patients were recorded. Results: Of patients, half were male, half were female, and the mean age was 58 years. The first three common diseases were diabetes mellitus, hypertension and coronary artery diseases. Of patients, %79.2 knew their illness. Fifty patients began to use drug within three months, 36 patient began to use within the last one year. While 42 patients brought all of their drugs with themselves, 17 patients brought along a portion of drugs. While three patients stopped their medication completely, 125 patients received medication on a regular basis. Fifty-two patient described the drugs with names, 13 patients described with their colors, 3 patients described by grammes, 45 patients described with the size of the tablet and 13 patients could not describe the drugs. Ninety-two patients explained which kind of drugs were used for each diseases, 17 patient explained partly, and 35 patients had no idea. Hundred patients received medication by themselves, 44 patients medications were giving by their relatives and med carers. Of medications, 140 were written by doctors directly, three medication were given by pharmacist; and one patient bought the drug by himself. For 11 patients the drugs were not harmonious to their diseases. Fifty-one patients admitted to the ED two times within last week, and 73 admitted two times within last month. Conclusion: The majority of patients with chronic diseases and use chronic drugs know their diseases and use the drugs in order, but do not have enough information about their medication.

Keywords: chronic disease, drug use, emergency department, medication

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2912 Mass Transfer of Paracetamol from the Crosslinked Carrageenan-Polyvinyl Alcohol Film

Authors: Sperisa Distantina, Rieke Ulfha Noviyanti, Sri Sutriyani, Fadilah Fadilah, Mujtahid Kaavessina

Abstract:

In this research, carrageenan extracted from seaweed Eucheuma cottonii was mixed with polyvinyl alcohol (PVA) and then crosslinked using glutaraldehyde (GA). The obtained hydrogel films were applied to control the drug release rate of paracetamol. The aim of this research was to develop a mathematical model that can be used to describe the mass transfer rate of paracetamol from the hydrogel film into buffer solution. The effect of weight ratio carrageenan-PVA (5: 0, 1: 0.5, 1: 1, 1: 2, 0: 5) on the parameters of the mathematical model was investigated also. Based on the experimental data, the proposed mathematical model could describe the mass transfer rate of paracetamol. The weight ratio of carrageenan-PVA greatly affected the amount of paracetamol absorbed in the hydrogel film and the mass transfer rate of paracetamol.

Keywords: carrageenan-PVA, crosslinking, glutaraldehyde, hydrogel, paracetamol, mass transfer

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2911 Discovery, Design and Synthesis of Some Novel Antitumor 1,2,4-Triazine Derivatives as C-Met Kinase Inhibitors

Authors: Ibrahim M. Labouta, Marwa H. El-Wakil, Hayam M. Ashour, Ahmed M. Hassan, Manal N. Saudi

Abstract:

The receptor tyrosine kinase c-Met is an attractive target for therapeutic treatment of cancers nowadays. Among the wide variety of heterocycles that have been explored for developing c-Met kinase inhibitors, the 1,2,4-triazines have been rarely investigated, although they are well known in the literature to possess antitumor activities. Herein we describe the design and synthesis of a novel series of 1,2,4-triazine derivatives possessing N-acylarylhydrazone moiety and another series combining the 1,2,4-triazine scaffold to the well-known anticancer drug 6-MP in order to explore their “double-drug” effect. The synthesized compounds were evaluated for their in vitro antitumor activity against three c-Met addicted cancer cell lines (A549, HT-29 and MKN-45). Most compounds showed moderate to excellent antiproliferative activity and four compounds showed potent inhibitory activity more than the reference drug Foretinib against one or more cancer cell lines. The obtained results revealed that the potent compounds are highly selective to A549 (lung adenocarcinoma) cancer cell line. The c-Met kinase inhibitory activity of the potent derivatives is still under investigation. The present study clearly demonstrates that the 1,2,4-triazine core ring exhibits promising antitumor activity with potential c-Met kinase inhibitory activity.

Keywords: 1, 2, 4-triazine, antitumor, c-Met inhibitor, double-drug

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2910 The Comparison of Chromium Ions Release Stainless Steel 18-8 between Artificial Saliva and Black Tea Leaves Extracts

Authors: Nety Trisnawaty, Mirna Febriani

Abstract:

The use of stainless steel wires in the field of dentistry is widely used, especially for orthodontic and prosthodontic treatment using stainless steel wire. The oral cavity is the ideal environment for corrosion, which can be caused by saliva. Prevention of corrosion on stainless steel wires can be done by using an organic or non-organic corrosion inhibitor. One of the organic inhibitors that can be used to prevent corrosion is black tea leaves extracts. To explain the comparison of chromium ions release for stainlees steel between artificial saliva and black tea leaves extracts. In this research we used artificial saliva, black tea leaves extracts, stainless steel wire and using Atomic Absorption Spectrophometric testing machine. The samples were soaked for 1, 3, 7 and 14 days in the artificial saliva and black tea leaves extracts. The results showed the difference of chromium ion release soaked in artificial saliva and black tea leaves extracts on days 1, 3, 7 and 14. Statistically, calculation with independent T-test with p < 0,05 showed a significant difference. The longer the duration of days, the more ion chromium were released. The conclusion of this study shows that black tea leaves extracts can inhibit the corrosion rate of stainless steel wires.

Keywords: chromium ion, stainless steel, artificial saliva, black tea leaves extracts

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2909 Early Stage Hydration of Wollastonite: Kinetic Aspects of the Metal-Proton Exchange Reaction

Authors: Nicolas Giraudo, Peter Thissen

Abstract:

In this paper we bring up new aspects of the metal proton exchange reaction (MPER, also called early stage hydration): (1) its dependence of the number of protons consumed by the preferential exchanged cations on the pH value applied at the water/wollastonite interface and (2) strong anisotropic characteristics detected in atomic force microscopy (AFM) and low energy ion scattering spectroscopy measurements (LEIS). First we apply density functional theory (DFT) calculations to compare the kinetics of the reaction on different wollastonite surfaces, and combine it with ab initio thermodynamics to set up a model describing (1) the release of Ca in exchange with H coming from the water/wollastonite interface, (2) the dependence of the MPER on the chemical potential of protons. In the second part of the paper we carried out in-situ AFM and inductive coupled plasma atomic emission spectroscopy (ICP-OES) measurements in order to evaluate the predicted values. While a good agreement is found in the basic and neutral regime (pH values from 14-4), an increasing mismatch appears in the acidic regime (pH value lower 4). This is finally explained by non-equilibrium etching, dominating over the MPER in the very acidic regime.

Keywords: anisotropy, calcium silicate, cement, density functional theory, hydration

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2908 Oral Versus Iontophoresis Nonsteroidal Anti-Inflammatory Drugs in Tennis Elbow

Authors: Moustafa Ali Elwan, Ibrahim Salem Abdelrafa, Ashraf Moharm

Abstract:

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed oral and topical drugs worldwide. Moreover, NSAIDs are responsible for most of all adverse drug reactions. For several decades, there are numerous attempts to use the cutaneous layers as a gate into the body for the local delivery of the therapeutic agent. Transdermal drug delivery is a validated technology contributing significantly to global pharmaceutical care. Transdermal Drug Delivery systems can be improved by using therapeutic agents. Moreover, Transdermal Drug Delivery systems can be improved by using chemical enhancers like ultrasound or iontophoresis. Iontophoresis provides a mechanism to enhance the penetration of hydrophilic and charged molecules across the skin. Objective: to compare the drug administration by ‘iontophoresis’ versus the oral rule. Methods: This study was conducted at the Faculty of Physical Therapy, Modern University for technology and information, Cairo, Egypt, on 20 participants (8 female & 12 male) who complained of tennis elbow. Their mean age was (25.45 ± 3.98) years, and all participants were assessed in many aspects: Pain threshold was assessed by algometer. Range of motion was assessed by electro goniometer, and isometric strength was assessed by a portable hand-held dynamometer. Then Participants were randomly assigned into two groups: group A was treated with oral NSAID (diclofenac) while group B was treated via administration of NSAIDs (diclofenac) via an iontophoresis device. All the participants were subjected to blood samples analysis in both pre-administration of the drug and post-administration of the drug for 24 hours (sample/every 6 hours). Results: The results demonstrated that there was a significant improvement in group b, “iontophoresis NSAIDs group,” more than in group B,” oral NSAIDs group,” in all measurements ‘ pain threshold, strength, and range of motion. Also, the iontophoresis method shows higher maximum plasma concentrations (Cmax) and concentration-time curves than the oral method.

Keywords: diclofenac, iontophoresis, NSAIDs, oral, tennis elbow

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