Search results for: drug resistant TB

Authors: Sreejani Barua, P. P. Srivastav

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Formulation of new functional food products for diabetes patients and obsessed people is a challenge for food industries till date. Starch is a certainly happening, ecological, reasonable and profusely obtainable polysaccharide in plant material. In the present scenario, there is a great interest in modifying starch functional properties without destroying its granular structure using different modification techniques. Resistant starch (RS) contains almost zero calories and can control blood glucose level to prevent diabetes. The current study focused on modification of mung bean starch which is a good source of legumes carbohydrate for the production of functional food. Heat moisture treatment (HMT) of mung starch was conducted at moisture content of 10-30%, temperature of 80-120 °C and time of 8-24 h.The content of resistant starch after modification was significantly increased from native starches containing RS 7.6%. The design combinations of HMT had been completed through Central Composite Rotatable Design (CCRD). The effects of HMT process variables on the yield of resistant starch was studied through Rapid Surface Methodology (RSM). The highest increase of resistant starch was found up to 34.39% when treated the native starch with 30% m.c at 120 °C temperature for 24 h.The functional properties of both native and modified mung bean starches showed that there was a reduction in the swelling power and swelling volume of HMT starches. However, the solubility of the HMT starches was higher than that of untreated native starch and also observed change in structural (scanning electron microscopy), X-Ray diffraction (XRD) pattern, blue value and thermal (differential scanning calorimetry) properties. Therefore, replacing native mung bean starch with heat-moisture treated mung bean starch leads to the development of new products with higher resistant starch levels and functional properties.

Keywords: Mung bean starch, heat moisture treatment, functional properties, resistant starch

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Authors: Maedeh Rahimnejad, Bahman Vahidi, Bahman Ebrahimi Hoseinzadeh, Fatemeh Yazdian, Puria Motamed Fath, Roghieh Jamjah

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Introduction: The intensive labor and high cost of developing new vehicles for controlled drug delivery highlights the need for a change in their discovery process. Computational models can be used to accelerate experimental steps and control the high cost of experiments. Methods: In this work, to better understand the interaction of anti-cancer drug and the nanocarrier with the cell membrane, we have done molecular dynamics simulation using NAMD. We have chosen paclitaxel for the drug molecule and dipalmitoylphosphatidylcholine (DPPC) as a natural phospholipid nanocarrier. Results: Next, center of mass (COM) between molecules and the van der Waals interaction energy close to the cell membrane has been analyzed. Furthermore, the simulation results of the paclitaxel interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane have been compared. Discussion: Analysis by molecular dynamics (MD) showed that not only the energy between the nanocarrier and the cell membrane is low, but also the center of mass amount decreases in the nanocarrier and the cell membrane system during the interaction; therefore they show significantly better interaction in comparison to the individual drug with the cell membrane.

Keywords: anti-cancer drug, center of mass, interaction energy, molecular dynamics simulation, nanocarrier

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Authors: Juliana Janet R. Martin-Puzon, Demetrio L. Valle, Windell L. Rivera

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This study aimed to determine the presence of bioactive phytochemical constituents and evaluate the in vitro antibacterial activities of Glinus oppositifolius or carpet weed, a plant valued for its use in traditional medicine and as a vegetable. The leaves, stems, and roots were extracted using chloroform, ethanol, and methanol. Phytochemical screening revealed that the entire G. oppositifolius plant, i.e. roots, stems, and leaves, is a rich source of alkaloids, flavonoids, glycosides, saponins, sterols, tannins, and triterpenes. The antibacterial activity of the leaf and stem extracts were evaluated through disc diffusion, minimum inhibitory concentration, and bactericidal concentration assays against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended spectrum β-lactamase-producing (ESβL+), carbapenem-resistant Enterobacteriaceae (CRE), and metallo-β-lactamase-producing (MβL+) Pseudomonas aeruginosa and Acinetobacter baumannii. The leaf extracts revealed antibacterial activities, inhibiting the growth of non-resistant and multidrug-resistant (MDR) strains of the Gram-negative bacteria E. coli, P. aeruginosa, and A. baumanii. In conclusion, the various biological activities of G. oppositifolius, including its antibacterial activity, are due to the presence of diverse bioactive secondary metabolites. The presence of phytochemical compounds in G. oppositifolius is scientific evidence on its use for treatment of many ailments. Thus, the results demonstrate the great potential of the plant as a new, alternative source of antimicrobials and other components with therapeutic value.

Keywords: antibacterial, Glinus oppositifolius, multidrug-resistant, secondary metabolites

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Authors: Babak Bahri, Fatemeh Yassaee Meybodi, Changiz Eslahchi

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In the pursuit of effective cancer therapies, the exploration of combinatorial drug regimens is crucial to leverage synergistic interactions between drugs, thereby improving treatment efficacy and overcoming drug resistance. However, identifying synergistic drug pairs poses challenges due to the vast combinatorial space and limitations of experimental approaches. This study introduces ClusterSyn, a machine learning (ML)-powered framework for classifying anti-cancer drug synergy scores. ClusterSyn employs a two-step approach involving drug clustering and synergy score prediction using a fully connected deep neural network. For each cell line in the training dataset, a drug graph is constructed, with nodes representing drugs and edge weights denoting synergy scores between drug pairs. Drugs are clustered using the Markov clustering (MCL) algorithm, and vectors representing the similarity of drug pairs to each cluster are input into the deep neural network for synergy score prediction (synergy or antagonism). Clustering results demonstrate effective grouping of drugs based on synergy scores, aligning similar synergy profiles. Subsequently, neural network predictions and synergy scores of the two drugs on others within their clusters are used to predict the synergy score of the considered drug pair. This approach facilitates comparative analysis with clustering and regression-based methods, revealing the superior performance of ClusterSyn over state-of-the-art methods like DeepSynergy and DeepDDS on diverse datasets such as Oniel and Almanac. The results highlight the remarkable potential of ClusterSyn as a versatile tool for predicting anti-cancer drug synergy scores.

Keywords: drug synergy, clustering, prediction, machine learning., deep learning

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Authors: Tadesse Eguale, Ephrem Engdawork, Wondwossen Gebreyes, Dainel Asrat, Hile Alemayehu, John Gunn

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Salmonella is one of the major zoonotic pathogens affecting wide range of vertebrates and humans worldwide. Consumption of contaminated dairy products and contact with dairy cattle represent the common sources of non-typhoidal Salmonella infection in humans. Fecal samples were collected from 132 dairy herds in central Ethiopia and cultured for Salmonella to determine the prevalence, serotype distribution and antimicrobial susceptibility. Salmonella was recovered from the feces of at least one cattle in 10(7.6%) of the dairy farms. Out of 1193 fecal samples 30(2.5%) were positive for Salmonella. Large farm size, detection of diarrhea in one or more animals during sampling and keeping animals completely indoor compared to occasional grazing outside were associated with Salmonella positivity of the farms. Farm level prevalence of Salmonella was significantly higher in young animals below 6 months of age compared to other age groups(X2=10.24; p=0.04). Nine different serotypes were isolated. The four most frequently recovered serotypes were S. Typhimurium (23.3%),S. Saintpaul (20%) and S. Kentucky and S. Virchow (16.7%) each. All isolates were resistant or intermediately resistant to at least one of the 18 drugs tested. Twenty-six (86.7%), 20(66.7%), 18(60%), 16(53.3%) of the isolates were resistant to streptomycin, nitrofurantoin, sulfisoxazole and tetracycline respectively. Resistance to 2 drugs was detected in 93.3% of the isolates. Resistance to 3 or more drugs were detected in 21(70%) of the total isolates while multi-drug resistance (MDR) to 7 or more drugs were detected in 12 (40%) of the isolates. The rate of occurrence of MDR in Salmonella strains isolated from dairy farms in Addis Ababa was significantly higher than those isolated from farms outside of Addis Ababa((p= 0.009). The detection of high MDR in Salmonella isolates originating from dairy farms warrants the need for strict pathogen reduction strategy in dairy cattle and spread of these MDR strains to human population.

Keywords: salmonella, antimicrobial resistance, fecal prevalence

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Authors: Dipali Nagaonkar, Mahendra Rai

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Chitosan, a carbohydrate polymer at nanoscale level has gained considerable momentum in drug delivery applications due to its inherent biocompatibility and non-toxicity. However, conventional synthetic strategies for chitosan nanoparticles mainly rely upon physicochemical techniques, which often yield chitosan microparticles. Hence, there is an emergent need for development of controlled synthetic protocols for chitosan nanoparticles within the nanometer range. In this context, we report the green synthesis of size controlled chitosan nanoparticles by using Pongamia pinnata (L.) leaf extract. Nanoparticle tracking analysis confirmed formation of nanoparticles with mean particle size of 85 nm. The stability of chitosan nanoparticles was investigated by zetasizer analysis, which revealed positive surface charged nanoparticles with zeta potential 20.1 mV. The green synthesized chitosan nanoparticles were further explored for encapsulation and controlled release of antioxidant biomolecule, quercetin. The resulting drug loaded chitosan nanoparticles showed drug entrapment efficiency of 93.50% with drug-loading capacity of 42.44%. The cumulative in vitro drug release up to 15 hrs was achieved suggesting towards efficacy of green synthesized chitosan nanoparticles for drug delivery applications.

Keywords: Chitosan nanoparticles, green synthesis, Pongamia pinnata, quercetin

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Authors: Zikora K. G. Anyaegbunam, Annabel A. Nnawuihe, Ngozi J. Anyaegbunam, Emmanuel A. Eze

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The discovery and production of new antibiotics is unavoidable in the fight against drug-resistant bacteria. However, this is only part of the problem; we have never really had medications that could completely eradicate an infection. All pathogens create a limited number of dormant persister cells that are resistant to antibiotic treatment. When the concentration of antibiotics decreases, surviving persisters repopulate the population, resulting in a recurrent chronic infection. Bacterial populations have an alternative survival strategy to withstand harsh conditions or antibiotic exposure, in addition to the well-known methods of antibiotic resistance and biofilm formation. Persister cells are a limited subset of transiently antibiotic-tolerant phenotypic variations capable of surviving high-dose antibiotic therapy. Persisters that flip back to a normal phenotype can restart growth when antibiotic pressure drops, assuring the bacterial population's survival. Persister cells have been found in every major pathogen, and they play a role in antibiotic tolerance in biofilms as well as the recalcitrance of chronic infections. Persister cells has been implicated to play a role in the establishment of antibiotic resistance, according to growing research. Thusthe need to basically elucidate the biology of persisters and how they are linked to antibiotic resistance, and as well it's link to diseases.

Keywords: persister cells, phenotypic variations, repopulation, mobile genetic transfers, antibiotic resistance

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Authors: Yogita Patil-Sen

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Magnetic nanoparticles such as those made of iron oxide have been widely explored as biocatalysts, contrast agents, and drug delivery systems. However, some of the challenges associated with these particles are agglomeration and biocompatibility, which lead to concern of toxicity of the particles, especially for drug delivery applications. Coating the particles with biocompatible materials such as lipids and peptides have shown to improve the mentioned issues. Thus, these core-shell type nanoparticles are emerging as the new class of nanomaterials for targeted drug delivery applications. In this study, various types of core-shell magnetic nanoparticles are prepared and characterized using techniques, such as Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Vibrating Sample Magnetometer (VSM) and Thermogravimetric Analysis (TGA). The heating ability of nanoparticles is tested under oscillating magnetic field. The efficacy of the nanoparticles as drug carrier is also investigated. The loading of an anticancer drug, Doxorubicin at 18 °C is measured up to 48 hours using UV-visible spectrophotometer. The drug release profile is obtained under thermal incubation condition at 37 °C and compared with that under the influence of oscillating field. The results suggest that the core-shell nanoparticles exhibit superparamagnetic behaviour, although, coating reduces the magnetic properties of the particles. Both the uncoated and coated particles show good heating ability, again it is observed that coating decreases the heating behaviour of the particles. However, coated particles show higher drug loading efficiency than the uncoated particles and the drug release is much more controlled under the oscillating magnetic field. Thus, the results strongly indicate the suitability of the prepared core-shell type nanoparticles as drug delivery vehicles and their potential in magnetic hyperthermia applications and for hyperthermia cancer therapy.

Keywords: core-shell, hyperthermia, magnetic nanoparticles, targeted drug delivery

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Authors: Vikram Chowdhary, Marek Vins

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The profitability of the pharmaceutical drug business has attracted considerable interest, but it also faces significant challenges. Counterfeiters take advantage of the industry's vulnerabilities, which are further exacerbated by the globalization of the market, online trading, and complex supply chains. Governments and organizations worldwide are dedicated to creating a secure environment that ensures a consistent and genuine supply of pharmaceutical products. In 2019, the European authorities implemented regulation EU 2016/161 to strengthen traceability and transparency throughout the entire drug supply chain. This regulation requires the addition of enhanced security features, such as serializing items to the saleable unit level or individual packs. Despite these efforts, the incidents of pharmaceutical counterfeiting continue to rise globally, with regulated territories being particularly affected. This paper examines the effectiveness of the drug serialization system implemented by European authorities. By conducting a systematic literature review, we assess the implementation of drug serialization and explore the potential benefits of integrating emerging digital technologies, such as RFID and Blockchain, to improve traceability and management. The objective is to fortify pharmaceutical supply chains against counterfeiters and manipulators and ensure their security.

Keywords: blockchain, counterfeit drugs, EU drug serialization, pharmaceutical industry, RFID

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Authors: Ode Kenneth Ogbu

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This study was designed as a survey to investigate the incidence of use and abuse of drug as a social problem among the Nigeria youths in the secondary schools in urban centres of Benue state. 500 SS 3 and fresh secondary school graduates in remedial science class of Benue State University Makurdi with mean age of 16.8 were randomly sampled for the study. An instrument called drug use and abuse perception questionnaire (DAPQ) with a reliability coefficient of 74 were administered to the students. Only 337 copies of the questionnaire were properly completed and returned which reduced the sample size of 337. The data were subjected to factor analysis. X2 statistic and frequency distribution using split half method. The result of the analysis showed that: the DAPQ yield seven baseline factors responsible for drug use and abuse; there was appreciable evidence that the study subjects used drugs (42.1%); alcohol topped the list of the drugs consumed; most students use their pocket money to buy drugs; drugs were purchased from unconventional, hidden places and 13 out of the 20 items of DAPQ were perceived as significant factors in drug use and abuse. The paper recommends proper intervention of government, parents and NGO’S among students to reduce cases of drug abuse.

Keywords: drug abuse, psychology, psychiatry, students

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Authors: Tasnuva Tamanna, Aimin Yu

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Application of nanoscience in biomedical field has come across as a new era. This study involves the synthesis of nano drug carrier with antibiotic loading. Based on the founding that polydopamine (PDA) nanoparticles could be formed via self-polymerization of dopamine at alkaline pH, one-step synthesis of rifampicin coupled polydopamine (PDA-R) nanoparticles was achieved by adding rifampicin into the dopamine solution. The successful yield of PDA nanoparticles with or without the presence of rifampicin during the polymerization process was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and Raman spectroscopy. Drug loading was monitored by UV-vis spectroscopy and the loading efficiency of rifampicin was calculated to be 76%. Such highly capacious nano-reservoir was found very stable with little drug leakage at pH 3.

Keywords: drug loading, nanoparticles, polydopamine, rifampicin

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Authors: Shahana Sharmin

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In the present study, the effect of cellulose polymers Ethyl Cellulose and Hydroxy Propyl Methyl Cellulose was evaluated on the release profile of drug from sustained release pellet. Diltiazem Hydrochloride, an antihypertensive, cardio-protective agent and slow channel blocker were used as a model drug to evaluate its release characteristics from different pellets formulations. Diltiazem Hydrochloride sustained release pellets were prepared by drug loading (drug binder suspension) on neutral pellets followed by different percentages of spraying, i.e. 2%,4%, 6%, 8% and 10% coating suspension using ethyl cellulose and hydroxy-propyl methyl cellulose polymer in a fixed 85:15 ratios respectively. The in vitro dissolution studies of Diltiazem Hydrochloride from these sustained release pellets were carried out in pH 7.2 phosphate buffer for 1, 2, 3, 4, 5, 6, 7, and 8 hrs using USP-I method. Statistically, significant differences were found among the drug release profile from different formulations. Polymer content with the highest concentration of Ethyl cellulose on the pellets shows the highest release retarding rate of the drug. The retarding capacity decreases with the decreased concentration of ethyl cellulose. The release mechanism was explored and explained with zero order, first order, Higuchi and Korsmeyer’s equations. Finally, the study showed that the profile and kinetics of drug release were functions of polymer type, polymer concentration & the physico-chemical properties of the drug.

Keywords: diltiazem hydrochloride, ethyl cellulose, hydroxy propyl methyl cellulose, release kinetics, sustained release pellets

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Authors: Zainab Dashti, Leila Vali

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Background: The Middle East, in particular Kuwait, contains one of the highest rates of patients with Diabetes in the world. Generally, infections resistant to antibiotics among the diabetic population has been shown to be on the rise. This is the first study in Kuwait to compare the antibiotic resistance profiles and genotypic differences between the resistant isolates of Enterobacteriaceae obtained from diabetic and non-diabetic patients. Material/Methods: In total, 65 isolates were collected from diabetic patients consisting of 34 E. coli, 15 K. pneumoniae and 16 other Enterobacteriaceae species (including Salmonella spp. Serratia spp and Proteus spp.). In our control group, a total of 49 isolates consisting of 37 E. coli, 7 K. pneumoniae and 5 other species (including Salmonella spp. Serratia spp and Proteus spp.) were included. Isolates were identified at the species level and antibiotic resistance profiles, including Colistin, were determined using initially the Vitek system followed by double dilution MIC and E-test assays. Multi drug resistance (MDR) was defined as isolates resistant to a minimum of three antibiotics from three different classes. PCR was performed to detect ESBL genes (blaCTX-M, blaTEM & blaSHV), flouroquinolone resistance genes (qnrA, qnrB, qnrS & aac(6’)-lb-cr) and carbapenem resistance genes (blaOXA, blaVIM, blaGIM, blaKPC, blaIMP, & blaNDM) in both groups. Pulse field gel electrophoresis (PFGE) was performed to compare clonal relatedness of both E. coli and K.pneumonaie isolates. Results: Colistin resistance was determined in three isolates with MICs of 32-128 mg/L. A significant difference in resistance to ampicillin (Diabetes 93.8% vs control 72.5%, P value <0.002), augmentin (80% vs 52.5%, p value < 0.003), cefuroxime (69.2% vs 45%, p value < 0.0014), ceftazadime (73.8% vs 42.5%, p value <0.001) and ciprofloxacin (67.6% vs 40%, p value < 0.005) were determined. Also, a significant difference in MDR rates between the two groups (Diabetes 76.9%, control 57.5%, p value <0.036 were found. All antibiotic resistance genes showed a higher prevalence among the diabetic group, except for blaCTX-M, which was higher among the control group. PFGE showed a high rate of diversity between each group of isolates. Conclusions: Our results suggested an alarming rate of antibiotic resistance, in particular Colistin resistance (1.8%) among K. pneumoniea isolated from diabetic patients in Kuwait. MDR among Enterobacteriaceae infections also seems to be a worrying issue among the diabetics of Kuwait. More efforts are required to limit the issue of antibiotic resistance in Kuwait, especially among patients with diabetes mellitus.

Keywords: antibiotic resistance, diabetes, enterobacreriacae, multi antibiotic resistance

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Authors: Hardeep

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The aim of this research work to improve the solubility and bioavailability of Simvastatin using a self nanoemulsifying drug delivery system (SNEDDS). Self emulsifying property of various oils including essential oils was evaluated with suitable surfactants and co-surfactants. Validation of a method for accuracy, repeatability, Interday and intraday precision, ruggedness, and robustness were within acceptable limits. The liquid SNEDDS was prepared and optimized using a ternary phase diagram, thermodynamic, centrifugation and cloud point studies. The globule size of optimized formulations was less than 200 nm which could be an acceptable nanoemulsion size range. The mean droplet size, drug loading, PDI and zeta potential were found to be 141.0 nm, 92.22%, 0.23 and -10.13 mV and 153.5nm, 93.89 % ,0.41 and -11.7 mV and 164.26 nm, 95.26% , 0.41 and -10.66mV respectively.

Keywords: simvastatin, self nanoemulsifying drug delivery system, solubility, bioavailability

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Authors: Nagasamy Venkatesh Dhandapani

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The objective of the present study was to develop sustained release oral matrix tablets of anti epileptic drug levetiracetam. The sustained release matrix tablets of levetiracetam were prepared using hydrophilic matrix hydroxypropyl methylcellulose (HPMC) as a release retarding polymer by wet granulation method. Prior to compression, FTIR studies were performed to understand the compatibility between the drug and excipients. The study revealed that there was no chemical interaction between drug and excipients used in the study. The tablets were characterized by physical and chemical parameters and results were found in acceptable limits. In vitro release study was carried out for the tablets using 0.1 N HCl for 2 hours and in phosphate buffer pH 7.4 for remaining time up to 12 hours. The effect of polymer concentration was studied. Different dissolution models were applied to drug release data in order to evaluate release mechanisms and kinetics. The drug release data fit well to zero order kinetics. Drug release mechanism was found as a complex mixture of diffusion, swelling and erosion.

Keywords: levetiracetam, sustained-release, hydrophilic matrix tablet, HPMC grade K 100 MCR, wet granulation, zero order release kinetics

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Authors: Mehdi Nasr-Esfahani, Leila Mohammad Bagheri, Ava Nasr-Esfahani

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Root and collar rot disease caused by Phytophthora capsici (Leonian) is one of the most serious diseases in pepper, Capsicum annuum L. In this study, a diverse collection of 37 commercial edible and ornamental pepper genotypes infected with P. capsici were investigated for biomass parameters and enzymatic activity of peroxidase or peroxide reductases (EC), superoxide dismutase (SOD), polyphenol oxidase (PPOs), catalase (CAT) and phenylalanine ammonia-lyase (PAL). Seven candidate DEG genes were also evaluated on resistant and susceptible pepper cultivars, through measuring product formation, using spectrophotometry and real-time polymerase chain reaction. All the five enzymes and seven defense-gene candidates were up-regulated in all inoculated pepper accessions to P. capsici. But, the enzymes and DEG genes were highly expressed in resistant cv. 19OrnP-PBI, 37ChillP-Paleo, and “23CherryP-Orsh". The expression level of enzymes were 1.5 to 5.6-fold higher in the resistant peppers, than the control non-inoculated genotypes. Also, the transcriptional levels of related candidate DEG genes were 3.16 to 5.90-fold higher in the resistant genotypes. There was a direct and high correlation coefficient between resistance, bio-mass parameters, enzymatic activity, and resistance gene expression. The related enzymes and candidate genes expressed herein will provide a basis for further gene cloning and functional verification studies, and also will aid in an understanding of the regulatory mechanism of pepper resistance to P. capsici.

Keywords: AP2/ERF, cDNA, enzymes, MIP gene, q-RTPCR, XLOC

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Authors: Waraporn Boonchieng, Ekkarat Boonchieng, Sivaporn Aungwattana, Decha Tamdee, Wongamporn Pinyavong

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Drug addiction represents one of the most important public health issues in both developed and developing countries. The purpose of this study was to develop a drug abuse health information in a community in Northern Thailand using developmental research design. The developmental researchers performed four phases to develop drug abuse health information, including 1) synthesizing knowledge related to drug abuse prevention and identifying the components of drug abuse health information; 2) developing the system in mobile application and website; 3) implementing drug abuse health information in the rural community; and 4) evaluating the feasibility of drug abuse health information. Data collection involved both qualitative and quantitative procedures. The qualitative data and quantitative data were analyzed using content analysis and descriptive statistics, respectively. The findings of this study showed that drug abuse health information consisted of five sections, including drug-related prevention knowledge for teens, drug-related knowledge for adults and professionals, the database for drug dependence treatment centers, self-administered questionnaires, and supportive counseling sections. First, in drug-related prevention knowledge for teens, the developmental researchers designed four infographics and animation to provide drug-related prevention knowledge, including types of illegal drugs, causes of drug abuse, consequences of drug abuse, drug abuse diagnosis and treatment, and drug abuse prevention. Second, in drug-related knowledge for adults and professionals, the developmental researchers developed many documents in a form of PDF file to provide drug-related knowledge, including types of illegal drugs, causes of drug abuse, drug abuse prevention, and relapse prevention guideline. Third, database for drug dependence treatment centers included the place, direction map, operation time, and the way for contacting all drug dependence treatment centers in Thailand. Fourth, self-administered questionnaires comprised preventive drugs behavior questionnaire, drug abuse knowledge questionnaire, the stages of change readiness and treatment eagerness to drug use scale, substance use behaviors questionnaire, tobacco use behaviors questionnaire, stress screening, and depression screening. Finally, for supportive counseling, the developmental researchers designed chatting box through which each user could write and send their concerns to counselors individually. Results from evaluation process showed that 651 participants used drug abuse health information via mobile application and website. Among all users, 48.8% were males and 51.2% were females. More than half (55.3%) were 15-20 years old and most of them (88.0%) were Buddhists. Most users reported ever getting knowledge related to drugs (86.1%), and drinking alcohol (94.2%) while some of them (6.9%) reported ever using tobacco. For satisfaction with using the drug abuse health information, more than half of users reflected that the contents of drug abuse health information were interesting (59%), up-to date (61%), and highly useful to their self-study (59%) at high level. In addition, half of them were satisfied with the design in terms of infographics (54%) and animation (51%). Thus, this drug abuse health information can be adopted to explore drug abuse situation and serves as a tool to prevent drug abuse and addiction among Thai community people.

Keywords: drug addiction, health informatics, big data, development research

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Authors: Katharigatta N. Venugopala, Melendhran Pillay, Bander E. Al-Dhubiab

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Tuberculosis (TB) infection is caused mainly by Mycobacterium tuberculosis (MTB) and it is one of the most threatening and wide spread infectious diseases in the world. Benzothiazole derivatives are found to have diverse chemical reactivity and broad spectrum of pharmacological activity. Some of the important pharmacological activities shown by the benzothiazole analogues are antitumor, anti-inflammatory, antimicrobial, anti-tubercular, anti-leishmanial, anticonvulsant and anti-HIV properties. Keeping all these facts in mind in the present investigation it was envisaged to synthesize a series of novel {2-(benzo[d]-thiazol-2-yl-methoxy)-substitutedaryl}-(substitutedaryl)-methanones (4a-f) and characterize by IR, NMR (1H and 13C), HRMS and single crystal x-ray studies. The title compounds are investigated for in vitro anti-tubercular activity against two TB strains such as H37Rv (ATCC 25177) and MDR-MTB (multi drug resistant MTB resistant to Isoniazid, Rifampicin and Ethambutol) by agar diffusion method. Among the synthesized compounds in the series, test compound {2-(benzo[d]thiazol-2-yl-methoxy)-5-fluorophenyl}-(4-chlorophenyl)-methanone (2c) was found to exhibit significant activity with MICs of 1 µg/mL and 2 µg/mL against H37Rv and MDR-MTB, respectively when compared to standard drugs. Single crystal x-ray studies was used to study intra and intermolecular interactions, including polymorphism behavior of the test compounds, but none of the compounds exhibited polymorphism behavior.

Keywords: benzothiazole analogues, characterization, crystallography, anti-TB activity

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Authors: Rafael Estrada, Cristian Ruiz Rueda

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Carbapenems are last-resort antibiotics used in clinical settings to treat antibiotic-resistant bacterial infections. Thus, the emergence and spread of resistance to carbapenems is a major public health concern. Here, we have studied a carbapenem-resistant Aeromonas veronii strain previously isolated from a water sample from Sam Simeon Creek (Hearst San Simeon State Park, CA). Analysis of this isolate using disk-diffusion, CarbaNP, eCIM and mCIM assays revealed that it was resistant to amoxicillin-clavulanic acid and all carbapenems tested and that this isolate produced a potentially novel carbapenemase of the Metallo-β-lactamase family. Whole genome sequencing analysis revealed that this A. veronii isolate carries a novel variant of the blacₚₕₐ class β-carbapenemase gene that was closely related to the blacₚₕₐ₇ gene of Aeromonas jandaei. This isolate also carried a novel variant of the blaₒₓₐ class D carbapenemase gene that was most closely related to the blaₒₓₐ-₉₁₂ gene found in other Aeromonas veronii isolates. Finally, we also identified a novel class C β-lactamase gene moderately related to the blaFₒₓ-₁₇ gene of Providencia stuartii and other blaFₒₓ variants identified in Klebsiella pneumoniae, Escherichia coli and other Enterobacteriaceae. Overall, our findings reveal that environmental isolates are an important reservoir of multiple carbapenemases and other β-lactamases of clinical significance.

Keywords: β-lactamases, carbapenem, antibiotic-resistant, aeromonas veronii

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Authors: Xing Ping Hu, Yuexun Tian, Jerome Hogsette

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Housefly, Musca domestica L., is a serious urban nuisance and public health/food safety concern. This study evaluated the topical toxicity of 17 essential oil components and 3 plant essential oils against permethrin-resistant adult females and insecticide-susceptible house fly strains. Results show that thymol had the lowest LD₅₀ values against permethrin-resistant strain (43.77 and 41.10 ug per fly) and permethrin-susceptible strain (35.19 and 29.16 ug per fly) at both 24- and 48-hours post treatments; (+)-Pulegone had the lowest LD₉₅ values against the permethrin-resistant strain (0.15 and 0.10 mg per fly) at 24- and 48-hours post treatments, whereas plant thyme oil had the lowest LD₉₅ value of 0.17 mg per fly at post-24h and post-48h against the permethrin-susceptible strain. Additionally, the LD₅₀s was slightly but not significantly negatively correlated with the boiling points of the compounds tested; but showed no correlation with the density and LogP. These results indicate that specific essential oils and compounds have topical insecticidal properties against house flies with low dose. They may have the potential for development as botanical insecticides.

Keywords: urban pest, public health, pest management, botanical chemical

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Authors: M. Sorahi Nobar, V. Niknam, H. Ebrahimzadeh, H. Soltanloo

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Fusarium graminearum is one of the most destructive crop diseases in the world. Infection occurs during the flowering period in warm and humid conditions. It causes reduction in yield. Moreover, harvested grain is often contaminated with mycotoxins and its acetylated derivatives. Fusarium mycotoxines are potent inhibitor of protein synthesis, and thereby presents hazards for both human and animal health. A rapid production of reactive oxygen intermediates, primarily superoxide and hydrogen peroxide at the site of attempted infection considered as key feature underlying successful pathogen recognition. Here, we compared the time course activity of superoxide dismutase (SOD) as a first line of defenses against ROS- induced oxidative burst between FHB- resistant Sumai3 and susceptible Falat at 48, 96 and 144 hours after infection. Our results showed that Sumai3 SOD activity increased with time and reached the highest-level 4 days after infection while in susceptible cultivar Falat, SOD activity decreased during the first 96 h. after infection. Decreased was followed by an increased at 6 days after infection. According to our results rapid induction of SOD activity in resistant cultivar may play an important role in resistance against FHB in wheat.

Keywords: Fusarium graminearum, mycotoxins, resistant cultivar, superoxide dismutase

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Authors: Tamer M. Shehata, Heba S. Elsewedy, Mashel Al Dosary, Alaa Elshehry, Mohamed A. Khedr, Maged E. Mohamed

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Objective: 2,4-Dichlorophenoxy acetic acid (2,4-D) is a well-known herbicide widely used as a weed killer. Recently, 2,4-D was rediscovered as a new anti-inflammatory agent through in silico as well as in-vivo experiments. However, poor solubility of 2,4-D could represent a problems during pharmaceutical development in addition to lower bioavailability. Solid dispersion (SD) refers to a group of solid products consisting of at least two different components, usually a hydrophobic drug and hydrophilic matrix. It is well known technique for enhancing drug solubility. Therefore, selecting SD as a tool for enhancing 2,4-D could be of great interest to the formulator. Method: In our project, several polymers were investigated (such as PEG, HPMC, citric acid and others) in addition to drug polymer ratios and its effect on solubility. Evaluation of drug polymer interaction was investigated through both Fourier Transform Infrared (FTIR) and Differential Scanning Calorimetry (DSC). Finally, in-vivo evaluation was performed for the best selected preparation through inflammatory response of rat induce hind paw. Results: Results indicated that, citric acid 2,4-D and in ratio of 0.75 : 1 showed modified the dissolution profile of the drug. The FTIR resltes indicated no significant chemical interaction, however DSC showed shifting of the drug melting point. Finally, Carragenan induced rat hind paw edema showed significant reduction of the drug solid dispersion in comparison to the pure drug, indicating rapid and complete absorption of the drug in solid dispersion form. Conclusion: Solid dispersion technology can be utilized efficiently to enhance the solubility of 2,4-D.

Keywords: solid dispersion, 2, 4-D solubility, carragenan induced edema

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Authors: Brajesh Tiwari, Yuvraj Dangi, Abhishek Jain, Ashok Jain

Abstract:

The purpose of the investigation was to evaluate the potential of sphingosomes as nanoscale drug delivery units for site-specific delivery of anti-cancer agents. Doxorubicin Hydrochloride (DOX) was selected as a model anti-cancer agent. Sphingosomes were prepared and loaded with DOX and optimized for size and drug loading. The formulations were characterized by Malvern zeta-seizer and Transmission Electron Microscopy (TEM) studies. Sphingosomal formulations were further evaluated for in-vitro drug release study under various pH profiles. The in-vitro drug release study showed an initial rapid release of the drug followed by a slow controlled release. In vivo studies of optimized formulations and free drug were performed on albino rats for comparison of drug plasma concentration. The in- vivo study revealed that the prepared system enabled DOX to have had enhanced circulation time, longer half-life and lower elimination rate kinetics as compared to free drug. Further, it can be interpreted that the formulation would selectively enter highly porous mass of tumor cells and at the same time spare normal tissues. To summarize, the use of sphingosomes as carriers of anti-cancer drugs may prove to be a fascinating approach that would selectively localize in the tumor mass, increasing the therapeutic margin of safety while reducing the side effects associated with anti-cancer agents.

Keywords: sphingosomes, anti-cancer, doxorubicin, formulation

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Authors: Rajinikanth Siddalingam, Poonguzhali Subramanian

Abstract:

The present study aims to prepare and evaluate the self-nano emulsifying drug delivery (SNEDDS) system to enhance the dissolution rate of a poorly soluble drug dutasteride. The formulation was prepared using capryol PGMC, Cremophor EL, and polyethylene glycol (PEG) 400 as oil, surfactant and co-surfactant, respectively. The pseudo-ternary phase diagrams with presence and absence of drug were plotted to find out the nano emulsification range and also to evaluate the effect of dutasteride on the emulsification behavior of the phases. Prepared SNEDDS formulations were evaluated for its particle size distribution, nano emulsifying properties, robustness to dilution, self-emulsification time, turbidity measurement, drug content and in-vitro dissolution. The optimized formulations are further evaluated for heating cooling cycle, centrifugation studies, freeze-thaw cycling, particle size distribution and zeta potential were carried out to confirm the stability of the formed SNEDDS formulations. The particle size, zeta potential and polydispersity index of the optimized formulation found to be 35.45 nm, -15.45 and 0.19, respectively. The in vitro results are revealed that the prepared formulation enhanced the dissolution rate of dutasteride significantly as compared with pure drug. The in vivo studies in was conducted using rats and the results are revealed that SNEDDS formulation has enhanced the bioavailability of dutasteride drug significantly as compared with raw drug. Based the results, it was concluded that the dutasteride-loaded SNEDDS shows potential to enhance the dissolution of dutasteride, thus improving the bioavailability and therapeutic effects.

Keywords: self-emulsifying drug delivery system, dutasteride, enhancement of bioavailability, dissolution enhancement

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Authors: Ana-Maria Gheldiu, Bianca M. Abrudan, Maria A. Neag, Laurian Vlase, Dana M. Muntean

Abstract:

Background information: The objective of this study was to investigate the effect of multiple-dose fluvoxamine on the pharmacokinetic profile of single-dose carvedilol in rats, in order to evaluate this possible drug-drug pharmacokinetic interaction. Methods: A preclinical study, in 28 white male Wistar rats, was conducted. Each rat was cannulated on the femoral vein, prior to being connected to BASi Culex ABC®. Carvedilol was orally administrated in rats (3.57 mg/kg body mass (b.m.)) in the absence of fluvoxamine or after a pre-treatment with multiple oral doses of fluvoxamine (14.28 mg/kg b.m.). The plasma concentrations of carvedilol were estimated by high performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters of carvedilol were analyzed by non-compartmental method. Results: After carvediol co-administration with fluvoxamine, an approximately 2-fold increase in the exposure of carvedilol was observed, considering the significantly elevated value of the total area under the concentration versus time curve (AUC₀₋∞). Moreover, an increase by approximately 145% of the peak plasma concentration was found, as well as an augmentation by approximately 230% of the half life time of carvedilol was observed. Conclusion: Fluvoxamine co-administration led to a significant alteration of carvedilol’s pharmacokinetic profile in rats, these effects could be explained by the existence of a drug-drug interaction mediated by CYP2D6 inhibition. Acknowledgement: This work was supported by CNCS Romania – project PNII-RU-TE-2014-4-0242.

Keywords: carvedilol, fluvoxamine, drug-drug pharmacokinetic interaction, rats

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Authors: Sumeet Dwivedi, Shweta Shriwas, Raghvendra Dubey

Abstract:

The number of products based on new drug delivery systems has significantly increased in the past few years, and this growth is expected to continue in the near future. These biopharmaceuticals present challenges to drug delivery scientists because of their unique nature and difficulty in delivery through conventional routes. Therefore, future research will focus on the delivery of these complex molecules through different routes, including oral, nasal, pulmonary, vaginal, rectal, etc. The aim of present study was to formulate and evaluate ethosomes of Plumeria indica flowers which may deliver the drug to targeted site more efficiently than marketed preparation and also overcome the problems related with oral administration of drug. The formulations were prepared with ethanol, lecithin, propylene glycol and were evaluated.

Keywords: ethosomes, herbal extract, plumeria alba, lecithin

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Authors: Elena K. Schneider, Johnny X. Huang, Vincenzo Carbone, Mark Baker, Mohammad A. K. Azad, Matthew A. Cooper, Jian Li, Tony Velkov

Abstract:

Ivacaftor is a novel CF trans-membrane conductance regulator (CFTR) potentiator that improves the pulmonary function for cystic fibrosis patients bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs that compete for the same plasma protein binding sites and impact the free drug concentration. This in turn could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This study compares the binding affinity of ivacaftor and co-administered CF drugs for human serum albumin (HSA) and α1-acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site selective probes. Due to their high plasma protein binding affinities, drug-drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole and loratadine. The significance of these drug-drug interactions is interpreted in terms of the pharmacodynamic/pharmacokinetic parameters and molecular docking simulations. The translational outcomes of the data are presented as recommendations for a staggered treatment regimen for future clinical trials which aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor.

Keywords: human α-1-acid glycoprotein, binding affinity, human serum albumin, ivacaftor, cystic fibrosis

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Authors: Cesar Torres, Robert Briber, Nam Sun Wang

Abstract:

Eye drops are the most commonly used treatment for short-term and long-term ophthalmic diseases. However, eye drops could deliver only about 5% of the functional ingredients contained in a burst dosage. To address the limitations of eye drops, the use of therapeutic contact lenses has been introduced. Drug-loaded contact lenses provide drugs a longer residence time in the tear film and hence, decrease the potential risk of side effects. Nevertheless, a major limitation of contact lenses as drug delivery devices is that most of the drug absorbed is released within the first few hours. This fact limits their use for extended release. The present study demonstrates the application of long-alkyl chain ionic surfactants on extending drug release kinetics from commercially available silicone hydrogel contact lenses. In vitro release experiments were carried by immersing drug-containing contact lenses in phosphate buffer saline at physiological pH. The drug concentration as a function of time was monitored using ultraviolet-visible spectroscopy. The results of the study demonstrate that release kinetics is dependent on the ionic surfactant weight percent in the contact lenses, and on the length of the hydrophobic alkyl chain of the ionic surfactants. The use of ionic surfactants in contact lenses can extend the delivery of drugs from a few hours to a few weeks, depending on the physicochemical properties of the drugs. Contact lenses embedded with ionic surfactants could be potential biomaterials to be used for extended drug delivery and in the treatment of ophthalmic diseases. However, ocular irritation and toxicity studies would be needed to evaluate the safety of the approach.

Keywords: contact lenses, drug delivery, controlled release, ionic surfactant

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Authors: Azwin Lubis, Rika Hapsari, Zahrah Hikmah, Anang Endaryanto, Ariyanto Harsono

Abstract:

Erythema Multiforme Exudativum Major (EMEM) is one of the drug allergy diseases. Drug allergies caused by isoniazid rarely causes EMEM. Cutaneous reactions caused by isoniazid were obtained in 0.98% of patients, but the precise occurrence of Steven Johnson’s Syndrome (SJS) and Toxic Epidermolisis Necrolisis (TEN) due to isoniazid is not known for certain. We present this case to show hypersensitivity of isoniazid in a child. Based on the history of drug intake, physical diagnostic tests, drug elimination and provocation; we established the diagnosis of isoniazid hypersensitivity. The child showed improvement on skin manifestation after stopped isoniazid therapy.

Keywords: erythema multiforme exudativum major, hypersensitivity, elimination test, provocation test

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Authors: Nitin Dwivedi, Jigna Shah

Abstract:

Aim and objective of study: This article indicates a comparison among various generations of dendrimers, a dendrimer is a bioactive material has repetitively branched molecule and used for delivery of various therapeutic active agents. This debut report compares the effect various generations of PPI dendrimers for brain targeting and management of neurodegenerative disorders potential on single platform. This report involves the study of the various mechanism of synthesis ligand anchored various generations PPI dendrimers deliver the drug directly to the CNS, prove their effectiveness in the management of the various neurodegenerative disease. Material and Methods: The Memantine an anti-Alzheimer drug loaded in different generations (3.0G, 4.0G, and 5.0G) of PPI dendrimers which were synthesized were synthesized. The various studies investigate the effect of PPI dendrimers generation on different characteristic parameters i.e. synthesis procedure, drug loading, release behavior, hemolysis profile at different concentration, MRI study for determine the route drug from olfactory transfer, animal model study in vitro, as well as in vivo performance. The outcomes of the investigation indicate drug delivery benefit as well as superior biocompatibility of 4.0G PPI dendrimer over 3.0G and 5.0G dendrimer, respectively. Results and Conclusion: The above study indicate the superiority of in drug delivery system with maximum drug utilization and minimize the drug dose for neurodegenerative disorder over 5.0G PPI dendrimers. So, 4.0G PPI dendrimers are the safe formulations for the symptomatic treatment of the neurodegenerative disorder. The fifth-generation poly(propyleneimine) (PPI) dendrimers, inherent toxicity due to the presence of many peripheral cationic groups is the major issue that limits their applicability.

Keywords: Alzheimer disease, generation, memantine, PPI

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