Search results for: pan drug resistance
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4980

Search results for: pan drug resistance

4770 Cyclic Liquefaction Resistance of Reinforced Sand

Authors: S. A. Naeini, Z. Eftekhari

Abstract:

Liquefaction phenomenon in sand is nowadays a classical soil mechanics subject. Using a cyclic triaxial test apparatus, we use non-woven geotextile reinforcement to improve the liquefaction resistance of sand. The layer configurations used are zero, one, two and three horizontal reinforcing layers in a triaxial test sample. The influences of the number of geotextile layers, and cyclic stress ratio (CSR) were studied and described. The results illustrated that the geotextile inclusion increases liquefaction resistance.

Keywords: liquefaction resistance, geotextile, sand, cyclic triaxial test, cyclic stress ratio

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4769 Fabrication and Characterization of Dissolvable Microneedle Patches Using Different Compositions and Ratios of Hyaluronic Acid and Zinc Oxide Nanoparticles

Authors: Dada Kolawole Segun

Abstract:

Transdermal drug delivery has gained popularity as a non-invasive method for controlled drug release compared to traditional delivery routes. Dissolvable transdermal patches have emerged as a promising platform for delivering a variety of drugs due to their ease of use. The objective of this research was to create and characterize dissolvable transdermal patches using various compositions and ratios of hyaluronic acid and zinc oxide nanoparticles. A micromolding technique was utilized to fabricate the patches, which were subsequently characterized using scanning electron microscopy, atomic force microscopy, and tensile strength testing. In vitro drug release studies were conducted to evaluate the drug release kinetics of the patches. The study found that the mechanical strength and dissolution properties of the patches were influenced by the hyaluronic acid and zinc oxide nanoparticle ratios used in the fabrication process. Moreover, the patches demonstrated controlled delivery of model drugs through the skin, highlighting their potential for transdermal drug delivery applications. The results suggest that dissolvable transdermal patches can be tailored to meet specific requirements for drug delivery applications using different compositions and ratios of hyaluronic acid and zinc oxide nanoparticles. This development has the potential to improve treatment outcomes and patient compliance in various therapeutic areas.

Keywords: transdermal drug delivery, characterization, skin permeation, biodegradable materials

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4768 Rapid Detection of Cocaine Using Aggregation-Induced Emission and Aptamer Combined Fluorescent Probe

Authors: Jianuo Sun, Jinghan Wang, Sirui Zhang, Chenhan Xu, Hongxia Hao, Hong Zhou

Abstract:

In recent years, the diversification and industrialization of drug-related crimes have posed significant threats to public health and safety globally. The widespread and increasingly younger demographics of drug users and the persistence of drug-impaired driving incidents underscore the urgency of this issue. Drug detection, a specialized forensic activity, is pivotal in identifying and analyzing substances involved in drug crimes. It relies on pharmacological and chemical knowledge and employs analytical chemistry and modern detection techniques. However, current drug detection methods are limited by their inability to perform semi-quantitative, real-time field analyses. They require extensive, complex laboratory-based preprocessing, expensive equipment, and specialized personnel and are hindered by long processing times. This study introduces an alternative approach using nucleic acid aptamers and Aggregation-Induced Emission (AIE) technology. Nucleic acid aptamers, selected artificially for their specific binding to target molecules and stable spatial structures, represent a new generation of biosensors following antibodies. Rapid advancements in AIE technology, particularly in tetraphenyl ethene-based luminous, offer simplicity in synthesis and versatility in modifications, making them ideal for fluorescence analysis. This work successfully synthesized, isolated, and purified an AIE molecule and constructed a probe comprising the AIE molecule, nucleic acid aptamers, and exonuclease for cocaine detection. The probe demonstrated significant relative fluorescence intensity changes and selectivity towards cocaine over other drugs. Using 4-Butoxytriethylammonium Bromide Tetraphenylethene (TPE-TTA) as the fluorescent probe, the aptamer as the recognition unit, and Exo I as an auxiliary, the system achieved rapid detection of cocaine within 5 mins in aqueous and urine, with detection limits of 1.0 and 5.0 µmol/L respectively. The probe-maintained stability and interference resistance in urine, enabling quantitative cocaine detection within a certain concentration range. This fluorescent sensor significantly reduces sample preprocessing time, offers a basis for rapid onsite cocaine detection, and promises potential for miniaturized testing setups.

Keywords: drug detection, aggregation-induced emission (AIE), nucleic acid aptamer, exonuclease, cocaine

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4767 SOCS1 Inhibits MDR1 in Mammary Cell Carcinoma Reverses Multidrug Resistance

Authors: Debasish Pradhan, Shaktiprasad Pradhan, Rakesh Kumar Pradhan, Gitanjali Tripathy

Abstract:

Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. The current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was a positive correlation between them. At that point, we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi, the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise, the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flow cytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS1 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: breast cancer, multidrug resistance, SOCS1 gene, MDR1 gene, RNA interference

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4766 Self-Carried Theranostic Nanoparticles for in vitro and in vivo Cancer Therapy with Real-Time Monitoring of Drug Release

Authors: Jinfeng Zhang, Chun-Sing Lee

Abstract:

The use of different nanocarriers for delivering hydrophobic pharmaceutical agents to tumor sites has garnered major attention. Despite the merits of these nanocarriers, further studies are needed for improving their drug loading capacities (typically less than 10%) and reducing their potential systemic toxicity. So development of alternative self-carried nanodrug delivery strategies without using any inert carriers is highly desirable. In this study, we developed a self-carried theranostic curcumin (Cur) nanodrug for highly effective cancer therapy in vitro and in vivo with real-time monitoring of drug release. With a biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed excellent dispersibility and outstanding stability in physiological environment, with drug loading capacity higher than 78 wt.%. Both confocal microscopy and flow cytometry confirmed the cellular fluorescent “OFF-ON” activation and real-time monitoring of Cur molecule release, showing its potential for cancer diagnosis. In vitro and in vivo experiments clearly show that therapeutic efficacy of the PEGylated Cur NPs is much better than that of free Cur. This self-carried theranostic strategy with real-time monitoring of drug release may open a new way for simultaneous cancer therapy and diagnosis.

Keywords: drug delivery, in vitro and in vivo cancer therapy, real-time monitoring, self-carried

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4765 Treatment of Porphyromonas gingivalis Induced Gingivitis in Albino Rats with Tetracycline-Loaded Nanochitosan, an Immunohistochemical Analysis

Authors: Rania Hanafi Said, Rasha Mohamed Taha

Abstract:

Background: By using nanoparticles as drug delivery, it may be possible to avoid the drawbacks of systemic antibiotic dosing, including bacterial antibiotic resistance. The goal of this study was to see how well tetracycline loaded on nanochitosan worked to treat gingival inflammation in albino rats caused by Porphyromonas gingivalis. The study analyzed immunohistochemically the localization of the pro-inflammatory cytokine Interleukin-1beta (IL-1β). Material and methods: In this study, fifty mature male albino rats weighing 150 to 180 grams each were used. They were randomly divided into five groups. We checked for weight changes in rats. Ten male albino rats were included in Group I, which served as a negative control group. Ten rats were included in Group II, where they were exposed once to Porphyromonas. Group III contained ten rats, which were treated the same as Group II plus daily injections of diluted tetracycline powder at the infection sites. Ten rats in Group IV received the same procedure as those in Group II before receiving daily injections of nanochitosan at the injection sites. Finally, Group V, which had ten rats. Following the same protocol as Group II, they received localized injections of tetracycline loaded on nanochitosan once daily. Rats' gingivae were extracted and prepared after they were anesthetized. The biopsies were examined histologically and immunohistochemically by light microscopy. Results: Groups I and V had a nearly normal histological appearance of gingival tissue. In Groups II, III, and IV, degeneration was seen because the epithelial cells were bigger, collagen fibers were pulling away from the lamina propria connective tissue, and the basement membranes had come to an end. There was no discernible difference between groups V and I when they were examined immunohistochemically. Conclusion: The use of nano chitosan as a tetracycline carrier is a novel technique to overcome the drug's rising level of resistance.

Keywords: Immunohistochemistry, Nanochitosan, porphyromonas gingivitis, Tetracycline

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4764 Pattern of Adverse Drug Reactions with Platinum Compounds in Cancer Chemotherapy at a Tertiary Care Hospital in South India

Authors: Meena Kumari, Ajitha Sharma, Mohan Babu Amberkar, Hasitha Manohar, Joseph Thomas, K. L. Bairy

Abstract:

Aim: To evaluate the pattern of occurrence of adverse drug reactions (ADRs) with platinum compounds in cancer chemotherapy at a tertiary care hospital. Methods: It was a retrospective, descriptive case record study done on patients admitted to the medical oncology ward of Kasturba Hospital, Manipal from July to November 2012. Inclusion criteria comprised of patients of both sexes and all ages diagnosed with cancer and were on platinum compounds, who developed at least one adverse drug reaction during or after the treatment period. CDSCO proforma was used for reporting ADRs. Causality was assessed using Naranjo Algorithm. Results: A total of 65 patients was included in the study. Females comprised of 67.69% and rest males. Around 49.23% of the ADRs were seen in the age group of 41-60 years, followed by 20 % in 21-40 years, 18.46% in patients over 60 years and 12.31% in 1-20 years age group. The anticancer agents which caused adverse drug reactions in our study were carboplatin (41.54%), cisplatin (36.92%) and oxaliplatin (21.54%). Most common adverse drug reactions observed were oral candidiasis (21.53%), vomiting (16.92%), anaemia (12.3%), diarrhoea (12.3%) and febrile neutropenia (0.08%). The results of the causality assessment of most of the cases were probable. Conclusion: The adverse effect of chemotherapeutic agents is a matter of concern in the pharmacological management of cancer as it affects the quality of life of patients. This information would be useful in identifying and minimizing preventable adverse drug reactions while generally enhancing the knowledge of the prescribers to deal with these adverse drug reactions more efficiently.

Keywords: adverse drug reactions, platinum compounds, cancer, chemotherapy

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4763 Evaluation of the Incidence of Mycobacterium Tuberculosis Complex Associated with Soil, Hayfeed and Water in Three Agricultural Facilities in Amathole District Municipality in the Eastern Cape Province

Authors: Athini Ntloko

Abstract:

Mycobacterium bovis and other species of Mycobacterium tuberculosis complex (MTBC) can result to a zoonotic infection known as Bovine tuberculosis (bTB). MTBC has members that may contaminate an extensive range of hosts, including wildlife. Diverse wild species are known to cause disease in domestic livestock and are acknowledged as TB reservoirs. It has been a main study worldwide to deliberate on bTB risk factors as a result and some studies focused on particular parts of risk factors such as wildlife and herd management. The significance of the study was to determine the incidence of Mycobacterium tuberculosis complex that is associated with soil, hayfeed and water. Questionnaires were administered to thirty (30) smallholding farm owners in the two villages (kwaMasele and Qungqwala) and three (3) three commercial farms (Fort Hare dairy farm, Middledrift dairy farm and Seven star dairy farm). Detection of M. tuberculosis complex was achieved by Polymerase Chain Reaction using primers for IS6110; whereas a genotypic drug resistance mutation was detected using Genotype MTBDRplus assays. Nine percent (9%) of respondents had more than 40 cows in their herd, while 60% reported between 10 and 20 cows in their herd. Relationship between farm size and vaccination for TB differed from forty one percent (41%) being the highest to the least five percent (5%). The highest number of respondents who knew about relationship between TB cases and cattle location was ninety one percent (91%). Approximately fifty one percent (51%) of respondents had knowledge about wild life access to the farms. Relationship between import of cattle and farm size ranged from nine percent (9%) to thirty five percent (35%). Cattle sickness in relation to farm size differed from forty three (43%) being the highest to the least three percent (3%); while thirty three percent (33%) of respondents had knowledge about health management. Respondents with knowledge about the occurrence of TB infections in farms were forty-eight percent (48%). The frequency of DNA isolation from samples ranged from the highest forty-five percent (45%) from water to the least twenty two percent (22%) from soil. Fort Hare dairy farm had the highest number of positive samples, forty four percent (44%) from water samples; whereas Middledrift dairy farm had the lowest positive from water, seventeen percent (17%). Twelve (22%) out of 55 isolates showed resistance to INH and RIF that is, multi-drug resistance (MDR) and nine percent (9%) were sensitive to either INH or RIF. The mutations at rpoB gene differed from 58% being the highest to the least (23%). Fifty seven percent (57%) of samples showed a S315T1 mutation while only 14% possessed a S531L in the katG gene. The highest inhA mutations were detected in T8A (80 %) and the least was observed in A16G (17%). The results of this study reveal that risk factors for bTB in cattle and dairy farm workers are a serious issue abound in the Eastern Cape of South Africa; with the possibility of widespread dissemination of multidrug resistant determinants in MTBC from the environment.

Keywords: hayfeed, isoniazid, multi-drug resistance, mycobacterium tuberculosis complex, polymerase chain reaction, rifampicin, soil, water

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4762 Formulation and Evaluation of TDDS for Sustained Release Ondansetron HCL Patches

Authors: Baljinder Singh, Navneet Sharma

Abstract:

The skin can be used as the site for drug administration for continuous transdermal drug infusion into the systemic circulation. For the continuous diffusion/penetration of the drugs through the intact skin surface membrane-moderated systems, matrix dispersion type systems, adhesive diffusion controlled systems and micro reservoir systems have been developed. Various penetration enhancers are used for the drug diffusion through skin. In matrix dispersion type systems, the drug is dispersed in the solvent along with the polymers and solvent allowed to evaporate forming a homogeneous drug-polymer matrix. Matrix type systems were developed in the present study. In the present work, an attempt has been made to develop a matrix-type transdermal therapeutic system comprising of ondansetron-HCl with different ratios of hydrophilic and hydrophobic polymeric combinations using solvent evaporation technique. The physicochemical compatibility of the drug and the polymers was studied by infrared spectroscopy. The results obtained showed no physical-chemical incompatibility between the drug and the polymers. The patches were further subjected to various physical evaluations along with the in-vitro permeation studies using rat skin. On the basis of results obtained form the in vitro study and physical evaluation, the patches containing hydrophilic polymers i.e. polyvinyl alcohol and poly vinyl pyrrolidone with oleic acid as the penetration enhancer(5%) were considered as suitable for large scale manufacturing with a backing layer and a suitable adhesive membrane.

Keywords: transdermal drug delivery, penetration enhancers, hydrophilic and hydrophobic polymers, ondansetron HCl

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4761 Pharmacovigilance: An Empowerment in Safe Utilization of Pharmaceuticals

Authors: Pankaj Prashar, Bimlesh Kumar, Ankita Sood, Anamika Gautam

Abstract:

Pharmacovigilance (PV) is a rapidly growing discipline in pharmaceutical industries as an integral part of clinical research and drug development over the past few decades. PV carries a breadth of scope from drug manufacturing to its regulation with safer utilization. The fundamental steps of PV not only includes data collection and verification, coding of drugs with adverse drug reactions, causality assessment and timely reporting to the authorities but also monitoring drug manufacturing, safety issues, product quality and conduction of due diligence. Standardization of adverse event information, collaboration of multiple departments in different companies, preparation of documents in accordance to both governmental as well as non-governmental organizations (FDA, EMA, GVP, ICH) are the advancements in discipline of PV. De-harmonization, lack of predictive drug safety models, improper funding by government, non-reporting, and non-acceptability of ADRs by developing countries and reports directly from patients to the monitoring centres respectively are the major road backs of PV. Mandatory pharmacovigilance reporting, frequent inspections, funding by government, educating and training medical students, pharmacists and nurses in this segment can bring about empowerment in PV. This area needs to be addressed with a sense of urgency for the safe utilization of pharmaceuticals.

Keywords: pharmacovigilance, regulatory, adverse event, drug safety

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4760 The Economic Value of Mastitis Resistance in Dairy Cattle in Kenya

Authors: Caleb B. Sagwa, Tobias O. Okeno, Alexander K. Kahi

Abstract:

Dairy cattle production plays an important role in the Kenyan economy. However, high incidences of mastitis is a major setback to the productivity in this industry. The current dairy cattle breeding objective in Kenya does not include mastitis resistance, mainly because the economic value of mastitis resistance has not been determined. Therefore this study aimed at estimating the economic value of mastitis resistance in dairy cattle in Kenya. Initial input parameters were obtained from literature on dairy cattle production systems in the tropics. Selection index methodology was used to derive the economic value of mastitis resistance. Somatic cell count (SCC) was used an indicator trait for mastitis resistance. The economic value was estimated relative to milk yield (MY). Economic values were assigned to SCC in a selection index such that the overall gain in the breeding goal trait was maximized. The option of estimating the economic value for SCC by equating the response in the trait of interest to its index response was considered. The economic value of mastitis resistance was US $23.64 while maximum response to selection for MY was US $66.01. The findings of this study provide vital information that is a pre-requisite for the inclusion of mastitis resistance in the current dairy cattle breeding goal in Kenya.

Keywords: somatic cell count, milk quality, payment system, breeding goal

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4759 Modeling the Moment of Resistance Generated by an Ore-Grinding Mill

Authors: Marinka Baghdasaryan, Tigran Mnoyan

Abstract:

The pertinence of modeling the moment of resistance generated by the ore-grinding mill is substantiated. Based on the ranking of technological indices obtained in the result of the survey among the specialists of several beneficiating plants, the factors determining the level of the moment of resistance generated by the mill are revealed. A priori diagram of the ranks is obtained in which the factors are arranged in the descending order of the impact degree on the level of the moment. The obtained model of the moment of resistance shows the technological character of the operation modes of the ore-grinding mill and can be used for improving the operation modes of the system motor-mill and preventing the abnormal mode of the drive synchronous motor.

Keywords: model, abnormal mode, mill, correlation, moment of resistance, rotational speed

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4758 The Effect of Increased Tip Area of Suction Caissons on the Penetration Resistance Coefficients

Authors: Ghaem Zamani, Farveh Aghaye Nezhad, Amin Barari

Abstract:

The installation process of caissons has usually been a challenging step in the design phase, especially in the case of suction-assisted installation. The engineering practice for estimating the caisson penetration resistance is primarily controlled by the resistance governed by inner and outer skirt friction and the tip resistance. Different methods have been proposed in the literature to evaluate the above components, while the CPT-based methodology has attained notable popularity among others. In this method, two empirical coefficients are suggested, k𝒻 and kp, which relate the frictional resistance and tip resistance to the cone penetration resistance (q𝒸), respectively. A series of jacking installation and uninstallation experiments for different soil densities were carried out in the offshore geotechnical laboratory of Aalborg University, Denmark. The main goal of these tests was to find appropriate values for empirical coefficients of the CPT-based method for the buckets with large embedment ratio (i.e., d/D=1, where d is the skirt length and D is the diameter) and increased tip area penetrated into dense sand deposits. The friction resistance effects were isolated during the pullout experiments; hence, the k𝒻 was back-measured from the tests in the absence of tip resistance. The actuator force during jacking installation equals the sum of frictional resistance and tip resistance. Therefore, the tip resistance of the bucket is calculated by subtracting the back-measured frictional resistance from penetration resistance; hence the relevant coefficient kp would be achieved. The cone penetration test was operated at different points before and after each installation attempt to measure the cone penetration resistance (q𝒸), and the average value of q𝒸 is used for calculations. The experimental results of the jacking installation tests indicated that a larger friction area considerably increased the penetration resistance; however, this effect was completely diminished when foundation suction-assisted penetration was used. Finally, the values measured for the empirical coefficient of the CPT-based method are compared with the highest expected and most probable values suggested by DNV(1992) for uniform thickness buckets.

Keywords: suction caisson, offshore geotechnics, cone penetration test, wind turbine foundation

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4757 Multidrug Resistance Mechanisms among Gram Negative Clinical Isolates from Egypt

Authors: Mona T. Kashef, Omneya M. Helmy

Abstract:

Multidrug resistant (MDR) bacteria have become a significant public health threat. The prevalence rates, of Gram negative MDR bacteria, are in continuous increase. However, few data are available about these resistant strains. Since, third generation cephalosporins are one of the most commonly used antimicrobials, we set out to investigate the prevalence, different mechanisms and clonal relatedness of multidrug resistance among third generation resistant Gram negative clinical isolates. A total of 114 Gram negative clinical isolates, previously characterized as being resistant to at least one of 3rd generation cephalosporins, were included in this study. Each isolate was tested, using Kirby Bauer disk diffusion method, against its assigned categories of antimicrobials. The role of efflux pump in resistance development was tested by the efflux pump inhibitor-based microplate assay using chloropromazine as an inhibitor. Detecting different aminoglycosides, β-lactams and quinolones resistance genes was done using polymerase chain reaction. The genetic diversity of MDR isolates was investigated using Random Amplification of Polymorphic DNA technique. MDR phenotype was detected in 101 isolates (89%). Efflux pump mediated resistance was detected in 49/101 isolates. Aminoglycosides resistance genes; armA and aac(6)-Ib were detected in one and 53 isolates, respectively. The aac(6)-Ib-cr allele, that also confers resistance to floroquinolones, was detected in 28/53 isolates. β-lactam resistance genes; blaTEM, blaSHV, blaCTX-M group 1 and group 9 were detected in 52, 29, 61 and 35 isolates, respectively. Quinolone resistance genes; qnrA, qnrB and qnrS were detectable in 2, 14, 8 isolates respectively, while qepA was not detectable at all. High diversity was observed among tested MDR isolates. MDR is common among 3rd generation cephalosporins resistant Gram negative bacteria, in Egypt. In most cases, resistance was caused by different mechanisms. Therefore, new treatment strategies should be implemented.

Keywords: gram negative, multidrug resistance, RAPD typing, resistance genes

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4756 PEG-b-poly(4-vinylbenzyl phosphonate) Coated Magnetic Iron Oxide Nanoparticles as Drug Carrier System: Biological and Physicochemical Characterization

Authors: Magdalena Hałupka-Bryl, Magdalena Bednarowicz, Ryszard Krzyminiewski, Yukio Nagasaki

Abstract:

Due to their unique physical properties, superparamagnetic iron oxide nanoparticles are increasingly used in medical applications. They are very useful carriers for delivering antitumor drugs in targeted cancer treatment. Magnetic nanoparticles (PEG-PIONs/DOX) with chemotherapeutic were synthesized by coprecipitation method followed by coating with biocompatible polymer PEG-derivative (poly(ethylene glycol)-block-poly(4-vinylbenzylphosphonate). Complete physicochemical characterization was carried out (ESR, HRTEM, X-ray diffraction, SQUID analysis) to evaluate the magnetic properties of obtained PEG-PIONs/DOX. Nanoparticles were investigated also in terms of their stability, drug loading efficiency, drug release and antiproliferative effect on cancer cells. PEG-PIONs/DOX have been successfully used for the efficient delivery of an anticancer drug into the tumor region. Fluorescent imaging showed the internalization of PEG-PIONs/DOX in the cytoplasm. Biodistribution studies demonstrated that PEG-PIONs/DOX preferentially accumulate in tumor region via the enhanced permeability and retention effect. The present findings show that synthesized nanosystem is promising tool for potential magnetic drug delivery.

Keywords: targeted drug delivery, magnetic properties, iron oxide nanoparticles, biodistribution

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4755 Blast Resistance Enhancement of Structures Subjected to Improvised Explosive Devices Attack: A Numerical Study

Authors: Michael I. Okereke, Ambrose I. Akpoyomare

Abstract:

This paper presents a numerical study of the impact mechanic of metallic and sandwich structures incorporate with blast resistance enhancements. The study focuses on structures that have been exposed to improvised explosives devices (IEDs) attacks. The results show numerical conclusions on mechanisms to ensure blast resistance enhancement for the applications studied in this work. The work has identified optimal panel configuration both in geometry and configurations to ensure optimal blast resistance response to such IEDs discharges. Findings from this work will drive improvements in especially military and civilian vehicles in countries where blast attacks on vehicular occupants are quite rampant like Pakistan and Afghanistan.

Keywords: blast resistance, blast enhancement, explosives, material behavior

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4754 Effect of Different Sterilization Processes on Drug Loaded Silicone-Hydrogel

Authors: Raquel Galante, Marina Braga, Daniela Ghisleni, Terezinha J. A. Pinto, Rogério Colaço, Ana Paula Serro

Abstract:

The sensitive nature of soft biomaterials, such as hydrogels, renders their sterilization a particularly challenging task for the biomedical industry. Widely used contact lenses are now studied as promising platforms for topical corneal drug delivery. However, to the best of the authors knowledge, the influence of sterilization methods on these systems has yet to be evaluated. The main goal of this study was to understand how different pairs drug-hydrogel would interact under an ozone-based sterilization method in comparison with two conventional processes (steam heat and gamma irradiation). For that, Si-Hy containing hydroxylethyl methacrylate (HEMA) and [tris(trimethylsiloxy)silyl]propyl methacrylate (TRIS) was produced and soaked in different drug solutions, commonly used for the treatment of ocular diseases (levofloxacin, chlorhexidine, diclofenac and timolol maleate). The drug release profiles and main material properties were evaluated before and after the sterilization. Namely, swelling capacity was determined by water uptake studies, transparency was accessed by UV-Vis spectroscopy, surface topography/morphology by scanning electron microscopy (SEM) and mechanical properties by performing tensile tests. The drug released was quantified by high performance liquid chromatography (HPLC). The effectiveness of the sterilization procedures was assured by performing sterility tests. Ozone gas method led to a significant reduction of drug released and to the formation of degradation products specially for diclofenac and levofloxacin. Gamma irradiation led to darkening of the loaded Si-Hys and to the complete degradation of levofloxacin. Steam heat led to smoother surfaces and to a decrease of the amount of drug released, however, with no formation of degradation products. This difference in the total drug released could be the related to drug/polymer interactions promoted by the sterilization conditions in presence of the drug. Our findings offer important insights that, in turn, could be a useful contribution to the safe development of actual products.

Keywords: drug delivery, silicone hydrogels, sterilization, gamma irradiation, steam heat, ozone gas

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4753 Stigmatizing Narratives: Analyzing Drug Use Depictions in U.K. Digital News Media

Authors: Ava Simone Arteaga

Abstract:

This research explores the portrayal of drug use in U.K. digital news media, a topic of critical importance due to its influence on addiction treatment, recovery efforts, and public perceptions. Substance use disorder (SUD) as one of the most stigmatized health conditions globally, with media representations playing a crucial role in shaping societal attitudes. Despite the impact of media portrayals, there has been no comprehensive analysis of drug-related representations in U.K. digital news media for over thirteen years. This study aims to fill this gap by analyzing contemporary digital news depictions of drug use, focusing on how these portrayals influence public perception and contribute to stigma. This research will examine tabloid, national, and regional East Midlands press sites to understand current trends in drug-related reporting. The study will build on previous research, such as the 2010 UKDPC study, which revealed that drug users were often vilified, and that coverage was predominantly focused on criminal justice rather than recovery. Given the rise in drug-related deaths in the U.K. and the exacerbation of the drug crisis post-Brexit, this analysis is timely and crucial. The findings are expected to reveal how digital media continues to perpetuate stigma and misinformation about drug use. By comparing these findings with U.S. studies, the research will contribute to a better understanding of cross-cultural differences in drug-related media representations and inform policy discussions. The U.K. Government's ten-year plan to combat illegal drugs, which emphasizes reducing stigma, will benefit from this research by highlighting the need for improved media representations. Additionally, the study will engage with recent U.K. and international research on media stigma towards SUD to provide a broader context and comparative perspective. Ultimately, this study aims to drive changes in media reporting and contribute to the development of more effective public policies and interventions. By addressing current gaps in research and providing evidence-based recommendations, this work seeks to support the U.K. Government’s objectives and improve the media’s role in addressing drug-related issues.

Keywords: addiction, UK news media, media representations, depiction of drug use

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4752 Emergence of Carbapenemase Escherichia Coli Isolates from the Little Egret (Egretta Garzetta) in Algeria

Authors: Bouaziz Amira, Zaatout Nawel

Abstract:

Background: Antimicrobial resistance is an urgent global health challenge in human and veterinary medicine, where migratory birds play a major role in the dissemination of multi-drug-resistant bacteria. The aim of this study was to screen for the presence of carbapenemase-producing Gram-negative bacteria (GNB) in the little egret (Egrettagarzetta) migratory bird stools in Algeria. Materials/Methods: In January 2014, 12 feacal samples were collected in Garaet El-Tarf, Oum El-Bouaghi city, Algeria. Samples were subjected to selective isolation of carbapenem-resistant GNB. Representative colonies were identified using the VITEK system. The obtained isolates were subjected to antibiotic susceptibility testing using the disc-diffusion method as well as carbapenemase production was verified by the modified Carba NP test. Results: In total, ten E. coli were obtained and were resistant to amoxicillin/clavulanic acid (100%), ertapenem (70%), cefoxitin (60%) cefotaxime (20%), cefepime (20%), ciprofloxacin (20%) and aztreonam (10%). The phenotypic detection results revealed that six out of the obtained strains were positive for the modified Carba NP test. Conclusion: The present study suggests that the little egret (Egretta garzetta) could be considered a reservoir of carbapenem-resistant Gram-negative bacteria.

Keywords: antimicrobial resistance, E. coli, Egretta garzetta, carbapenem resistance, dissemination

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4751 Standardization of a Methodology for Quantification of Antimicrobials Used for the Treatment of Multi-Resistant Bacteria Using Two Types of Biosensors and Production of Anti-Antimicrobial Antibodies

Authors: Garzon V., Bustos R., Salvador J. P., Marco M. P., Pinacho D. G.

Abstract:

Bacterial resistance to antimicrobial treatment has increased significantly in recent years, making it a public health problem. Large numbers of bacteria are resistant to all or nearly all known antimicrobials, creating the need for the development of new types of antimicrobials or the use of “last line” antimicrobial drug therapies for the treatment of multi-resistant bacteria. Some of the chemical groups of antimicrobials most used for the treatment of infections caused by multiresistant bacteria in the clinic are Glycopeptide (Vancomycin), Polymyxin (Colistin), Lipopeptide (Daptomycin) and Carbapenem (Meropenem). Molecules that require therapeutic drug monitoring (TDM). Due to the above, a methodology based on nanobiotechnology based on an optical and electrochemical biosensor is being developed, which allows the evaluation of the plasmatic levels of some antimicrobials such as glycopeptide, polymyxin, lipopeptide and carbapenem quickly, at a low cost, with a high specificity and sensitivity and that can be implemented in the future in public and private health hospitals. For this, the project was divided into five steps i) Design of specific anti-drug antibodies, produced in rabbits for each of the types of antimicrobials, evaluating the results by means of an immunoassay analysis (ELISA); ii) quantification by means of an electrochemical biosensor that allows quantification with high sensitivity and selectivity of the reference antimicrobials; iii) Comparison of antimicrobial quantification with an optical type biosensor; iv) Validation of the methodologies used with biosensor by means of an immunoassay. Finding as a result that it is possible to quantify antibiotics by means of the optical and electrochemical biosensor at concentrations on average of 1,000ng/mL, the antibodies being sensitive and specific for each of the antibiotic molecules, results that were compared with immunoassays and HPLC chromatography. Thus, contributing to the safe use of these drugs commonly used in clinical practice and new antimicrobial drugs.

Keywords: antibiotics, electrochemical biosensor, optical biosensor, therapeutic drug monitoring

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4750 Development of Drug Delivery Systems for Endoplasmic Reticulum Amino Peptidases Modulators Using Electrospinning

Authors: Filipa Vasconcelos

Abstract:

The administration of endoplasmic reticulum amino peptidases (ERAP1 or ERAP2) inhibitors can be used for therapeutic approaches against cancer and auto-immune diseases. However, one of the main shortcomings of drug delivery systems (DDS) is associated with the drug off-target distribution, which can lead to an increase in its side effects on the patient’s body. To overcome such limitations, the encapsulation of four representative compounds of ERAP inhibitors into Polycaprolactone (PCL), Polyvinyl-alcohol (PVA), crosslinked PVA, and PVA with nanoparticles (liposomes) electrospun fibrous meshes is proposed as a safe and controlled drug release system. The use of electrospun fibrous meshes as a DDS allows efficient solvent evaporation giving limited time to the encapsulated drug to recrystallize, continuous delivery of the drug while the fibers degrade, prevention of initial burst release (sustained release), tunable dosages, and the encapsulation of other agents. This is possible due to the fibers' small diameters and resemblance to the extracellular matrix (confirmed by scanning electron microscopy results), high specific surface area, and good mechanical strength/stability. Furthermore, release studies conducted on PCL, PVA, crosslinked PVA, and PVA with nanoparticles (liposomes) electrospun fibrous meshes with each of the ERAP compounds encapsulated demonstrated that they were capable of releasing >60%, 50%, 40%, and 45% of the total ERAP concentration, respectively. Fibrous meshes with ERAP_E compound encapsulated achieved higher released concentrations (75.65%, 62.41%, 56.05%, and 65.39%, respectively). Toxicity studies of fibrous meshes with encapsulated compounds are currently being accessed in vitro, as well as pharmacokinetics and dynamics studies. The last step includes the implantation of the drug-loaded fibrous meshes in vivo.

Keywords: drug delivery, electrospinning, ERAP inhibitors, liposomes

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4749 Iontophoretic Drug Transport of Some Anti-Diabetic Agents

Authors: Ashish Jain, Satish Nayak

Abstract:

Transdermal iontophoretic drug delivery system is viable drug delivery platform technology and has a strong market worldwide. Transdermal drug delivery system is particularly desirable for therapeutic agents that need prolonged administration at controlled plasma level. This makes appropriateness to antihypertensive and anti-diabetic agents for their transdermal development. Controlled zero order absorption, easily termination of drug delivery and easy to administration also support for popularity of transdermal delivery. In this current research iontophoretic delivery of various anti diabetic agents like glipizide, glibenclamide and glimepiride were carried out. The experiments were carried out at different drug concentrations and different current densities using cathodal iontophoresis. Diffusion cell for iontophoretic permeation study was modified according to Glikfield Design. Pig skin was used for in vitro permeation study and for the in-vivo study New Zealand rabbits were used. At all concentration level iontophoresis showed enhanced permeation rate compared to passive controls. Iontophoretic transports of selected drugs were found to be increased with the current densities. Results showed that target permeation rate for selected drugs could be achieved with the aid of iontophoresis by increasing the area in an appreciable range.

Keywords: transdermal, iontophoresis, pig skin, rabbits, glipizide, glibeclamide

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4748 Inhibition of 3-Deoxy-D-Arabino-Heptulosonate 7-Phosphate Synthase from Mycobacterium Tuberculosis Using High Throughput Virtual Screening and Molecular Dynamics Studies

Authors: Christy Rosaline, Rathankar Roa, Waheeta Hopper

Abstract:

Persistence of tuberculosis, emergence of multidrug-resistance and extensively drug-resistant forms of the disease, has increased the interest in developing new antitubercular drugs. Developing inhibitors for 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis (MtbDAH7Ps), an enzyme involved in shikimate pathway, gives a selective target for antitubercular agents. MtbDAH7Ps was screened against ZINC database, and shortlisted compounds were subjected to induce fit docking. Prime/Molecular Mechanics Generalized Born Surface Area calculation was used to validate the binding energy of ligand-protein complex. Molecular Dynamics analysis for of the lead compounds–MtbDAH7Ps complexes showed that the backbone of MtbDAH7Ps in their complexes were stable. These results suggest that the shortlisted lead compounds ZINC04097114, ZINC15163225, ZINC16857013, ZINC06275603, and ZINC05331260 could be developed into novel drug leads to inhibit DAH7Ps in Mycobacterium tuberculosis.

Keywords: MtbDAH7Ps, Mycobacterium tuberculosis, HTVS, molecular dynamics

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4747 Evaluation of Fire Resistance of High Strength Reinforced Concrete Columns with Spiral Wire Rope

Authors: Ki-Seok Kwon, Heung-Youl Kim

Abstract:

This research evaluated fire resistances of high-strengthened reinforced concrete (RC) column, spiral wire rope which applied with 60, and 100MPa. The fire resistance test of RC column with loading condition was conducted following the ISO 834 (3 hours). This experiment set mixing of fiber (PP fiber, Steel fiber) and types of horizontal reinforcement as a variable of reinforcement method. The fire resistance test measured the main steel bar’s max and mean temperatures also the shrinkage and shrinking ratio of columns(500 X 500 X 3,000mm) with loadings. As a result, the specimen of 60MPa attained three hours fire resistance with only spiral wire rope. Also, the specimen of 100MPa must be reinforced with fibers and spiral wire rope to attain three hours fire resistance.

Keywords: reinforced concrete column, high strength concrete, wire rope, fire resistance test

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4746 Current Practices of Permitted Daily Exposure (PDE) Calculation and Selection

Authors: Annie Ramanbhai Mecwan

Abstract:

Cleaning validation in a pharmaceutical manufacturing facility is documented evidence that a cleaning process has effectively removed contaminants, residues from previous drug products and cleaning agents below a pre-defined threshold from the reusable tools and parts of equipment. In shared manufacturing facilities more than one drug product is prepared. After cleaning of reusable tools and parts of equipment after one drug product manufacturing, there are chances that some residues of drug substance from previously manufactured drug products may be retained on the equipment and can carried forward to the next drug product and thus cause cross-contamination. Health-based limits through the derivation of a safe threshold value called permitted daily exposure (PDE) for the residues of drug substances should be employed to identify the risks posed at these manufacturing facilities. The PDE represents a substance-specific dose that is unlikely to cause an adverse effect if an individual is exposed to or below this dose every day for a lifetime. There are different practices to calculate PDE. Data for all APIs in the public domain are considered to calculate PDE value though, company to company may vary the final PDE value based on different toxicologist’s perspective or their subjective evaluation. Hence, Regulatory agencies should take responsibility for publishing PDE values for all APIs as it is done for elemental PDEs. This will harmonize the PDE values all over the world and prevent the unnecessary load on manufacturers for cleaning validation

Keywords: active pharmaceutical ingredient, good manufacturing practice, NOAEL, no observed adverse effect level, permitted daily exposure

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4745 Drug Abuse among Immigrant Youth in Canada

Authors: Qin Wei

Abstract:

There has been an increased number of immigrants arriving in Canada and a concurrent rise in the number of immigrant youth suffering from drug abuse. Immigrant youths’ drug abuse has become a significant social and public health concern for researchers. This literature review explores the nature of immigrant youths’ drug abuse by examining the factors influencing the onset of substance misuse, the barriers that discourage youth to seek out treatment, and how to resolve addictions amidst immigrant youth. Findings from the literature demonstrate that diminished parental supervision, acculturation challenges, peer conformity, discrimination, and ethnic marginalization are all significant factors influencing youth to use drugs as an outlet for their pain, while culturally competent care and fear of family and culture-based addiction stigma act as barriers discouraging youth from seeking out addiction support. To resolve addiction challenges amidst immigrant youth, future research should focus on promoting and implementing culturally sensitive practices and psychoeducational initiatives into immigrant communities and within public health policies.

Keywords: approaches, barriers, drug abuse, Canada, immigrant youth, reasons

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4744 The Role of Medical Professionals in Imparting Drug Abuse Education to Secondary School Children

Authors: Hana Ashique, Florence Onabanjo

Abstract:

Objectives: Research on drug abuse education in secondary schools has highlighted the discrepancy between drug policies and practice. Drug abuse is closely associated with child mental health, and with increasing drug overdose deaths in the UK, approximately doubling in the last 30 years, it becomes important to revolutionise drug abuse education. Medical professionals from the University of Nottingham piloted a drug abuse workshop at a state school in Nottingham for children between the age of 14-15 years. An interactive and educational approach was implemented, which explained addiction from a medical perspective. The workshop aimed to debunk medical beliefs children harboured about drugs and to support children in making informed drug choices. Methods: The sample group consisted of six cohorts of 30 children from year 10. The workshop was delivered in three segments to each cohort. In the first segment, the children were introduced to the physiological mechanisms behind drug dependence and reward pathways. The second segment consisted of interactive discussions between the children and medical professionals. This also involved conversations between the children about their perspectives on drug abuse, thereby co-creating knowledge. The third segment used art to incorporate storytelling from the perspective of a year ten child. This exercise investigated the causes that led children to abuse drugs. A feedback questionnaire was distributed among the children to analyse the impact of the workshop. Results: The children answered eight questions. 56% agreed/strongly agreed that they found being taught by medical professionals effective. 50% disagreed, strongly disagreed, or felt neutral that they had received sufficient education about drug abuse previously. Notably, 20% agreed that they feel more likely to ask for help from a medical professional or organisation if they need it. Conclusion: The results highlighted the relevance of medical professionals to function as peer educators in drug abuse education to secondary school children. This would build trust between children and the medical profession within the community. However, a minority proportion of children showed keenness to seek support from medical professionals or organisations for their mental health if they needed it. This exposed the anxiety children have in coming forward to seek professional help. In order to work towards a child-centred approach, educational policies and practices need to align. Similar workshops and research may need to be conducted to expose different perspectives toward drug abuse education.

Keywords: adolescent mental health, evidence-based teaching, drug abuse awareness, medical professional led workshops

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4743 Induction of HIV-1 Resistance: The New Approaches Based on Gene Modification and Stem Cell Engineering

Authors: Alieh Farshbaf

Abstract:

Introduction: Current anti-retroviral drugs have some restrictions for treatment of HIV-1 infection. The efficacy of retroviral drugs is not same in different infected patients and the virus rebound from latent reservoirs after stopping them. Recently, the engineering of stem cells and gene therapy provide new approaches to eliminate some drug problems by induction of resistance to HIV-1. Literature review: Up to now, AIDS-restriction genes (ARGs) were suitable candidate for gene and cell therapies, such as cc-chemokine receptor-5 (CCR5). In this manner, CCR5 provide effective cure in Berlin and Boston patients by inducing of HIV-1 resistance with allogeneic stem cell transplantation. It is showed that Zinc Finger Nuclease (ZFN) could induce HIV-1 resistance in stem cells of infected patients by homologous recombination or non-end joining mechanism and eliminate virus loading after returning the modified cells. Then, gene modification by HIV restriction factors, as TRIM5, introduced another gene candidate for HIV by interfering in infection process. These gene modifications/editing provided by stem cell futures that improve treatment in refractory disease such as HIV-1. Conclusion: Although stem cell transplantation has some complications, but in compare to retro-viral drugs demonstrated effective cure by elimination of virus loading. On the other hand, gene therapy is cost-effective for an infected patient than retroviral drugs payment in a person life-long. The results of umbilical cord blood stem cell transplantation showed that gene and cell therapy will be applied easier than previous treatment of AIDS with high efficacy.

Keywords: stem cell, AIDS, gene modification, cell engineering

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4742 Iontophoretic Drug Transport: An Non-Invasive Transdermal Approach

Authors: Ashish Jain, Shivam Tayal

Abstract:

There has been great interest in the field of Iontophoresis since few years due to its great applications in the field of controlled transdermal drug delivery system. It is an technique which is used to enhance the transdermal permeation of ionized high molecular weight molecules across the skin membrane especially Peptides & Proteins by the application of direct current of 1-4 mA for 20-40 minutes whereas chemical must be placed on electrodes with same charge. Iontophoresis enhanced the delivery of drug into the skin via pores like hair follicles, sweat gland ducts etc. rather than through stratum corneum. It has wide applications in the field of experimental, Therapeutic, Diagnostic, Dentistry etc. Medical science is using it to treat Hyperhidrosis (Excessive sweating) in hands and feet and to treat other ailments like hypertension, Migraine etc. Nowadays commercial transdermal iontophoretic patches are available in the market to treat different ailments. Researchers are keen to research in this field due to its vast applications and advantages.

Keywords: iontophoresis, novel drug delivery, transdermal, permeation enhancer

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4741 Effect of Three Resistance Training Methods on Performance-Related Variables of Powerlifters

Authors: K. Shyamnath, K. Suresh Kutty

Abstract:

The purpose of the study was to find out the effect of three resistance training methods on performance-related variables of powerlifters. A total of forty male students (N=40) who had participated in Kannur University powerlifting championship were selected as subjects. The age group of the subjects ranged from 18 years old to 25 years old. The selected subjects were equally divided into four groups (n=10) of three experimental groups and a control group. The experimental Group I underwent traditional resistance training (TRTG), Group II underwent combined traditional resistance training and plyometrics (TRTPG), and Group III underwent combined traditional resistance training and resistance training with high rhythm (TRTHRG). Group IV acted as the control group (CG) receiving no training during the experimental period. The duration of the experimental period was sixteen weeks, five days per week. Powerlifting performance was assessed by the 1RM test in the squat, bench press and deadlift. Performance-related variables assessed were chest girth, arm girth, forearm girth, thigh girth, and calf girth. Pre-test and post-test were conducted a day before and two days after the experimental period on all groups. Analysis of covariance (ANCOVA) was applied to analyze the significant difference. The 0.05 level of confidence was fixed as the level of significance to test the F ratio obtained by the analysis of covariance. The result indicates that there is a significant effect of all the selected resistance training methods on the performance and selected performance-related variables of powerlifters. Combined traditional resistance training and plyometrics and combined traditional resistance training and resistance training with high rhythm proved better than the traditional resistance training in improving performance and selected performance-related variables of powerlifters. There was no significant difference between combined traditional resistance training and plyometrics and combined traditional resistance training and resistance training with high rhythm in improving performance and selected performance-related variables of powerlifters.

Keywords: girth, plyometrics, powerlifting, resistance training

Procedia PDF Downloads 489