Search results for: Anti-cancer drug
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 242

Search results for: Anti-cancer drug

212 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 paper 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 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 incompetent 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.

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211 Chitosan/Casein Microparticles: Preparation, Characterization and Drug Release Studies

Authors: Selvakumar Dhanasingh, Shunmuga Kumar Nallaperumal

Abstract:

Microparticles carrier systems made from naturally occurring polymers based on chitosan/casein system appears to be a promising carrier for the sustained release of orally and parenteral administered drugs. In the current study we followed a microencapsulation technique based aqueous coacervation method to prepare chitosan/casein microparticles of compositions 1:1, 1:2 and 1:5 incorporated with chloramphenicol. Glutaraldehyde was used as a chemical cross-linking agent. The microparticles were prepared by aerosol method and studied by optical microscopy, infrared spectroscopy, thermo gravimetric analysis, swelling studies and drug release studies at various pH. The percentage swelling of the polymers are found to be in the order pH 4 > pH 10 > pH 7 and the increase in casein composition decrease the swelling percentage. The drug release studies also follow the above order.

Keywords: Chitosan/casein micro particles, chloramphenicol, drug release, microencapsulation.

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210 Formulation of Extended-Release Gliclazide Tablet Using a Mathematical Model for Estimation of Hypromellose

Authors: Farzad Khajavi, Farzaneh Jalilfar, Faranak Jafari, Leila Shokrani

Abstract:

Formulation of gliclazide in the form of extended-release tablet in 30 and 60 mg dosage forms was performed using hypromellose (HPMC K4M) as a retarding agent. Drug-release profiles were investigated in comparison with references Diamicron MR 30 and 60 mg tablets. The effect of size of powder particles, the amount of hypromellose in formulation, hardness of tablets, and also the effect of halving the tablets were investigated on drug release profile. A mathematical model which describes hypromellose behavior in initial times of drug release was proposed for the estimation of hypromellose content in modified-release gliclazide 60 mg tablet. This model is based on erosion of hypromellose in dissolution media. The model is applicable to describe release profiles of insoluble drugs. Therefore, by using dissolved amount of drug in initial times of dissolution and the model, the amount of hypromellose in formulation can be predictable. The model was used to predict the HPMC K4M content in modified-release gliclazide 30 mg and extended-release quetiapine 200 mg tablets.

Keywords: Hypromellose, gliclazide, drug release, modified-release tablet, mathematical model.

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209 Zinc Oxide Nanoparticles Modified with Galactose as Potential Drug Carrier with Reduced Releasing of Zinc Ions

Authors: Jolanta Pulit-Prociak, Olga Długosz, Marcin Banach

Abstract:

The toxicity of bare zinc oxide nanoparticles used as drug carriers may be the result of releasing zinc ions. Thus, zinc oxide nanoparticles modified with galactose were obtained. The process of their formation was conducted in the microwave field. The physicochemical properties of the obtained products were studied. The size and electrokinetic potential were defined by using dynamic light scattering technique. The crystalline properties were assessed by X-ray diffractometry. In order to confirm the formation of the desired products, Fourier-transform infrared spectroscopy was used. Releasing of zinc ions from the prepared products when comparing to the bare oxide was analyzed. It was found out that modification of zinc oxide nanoparticles with galactose limits the releasing of zinc ions which are responsible for the toxic effect of the whole carrier-drug conjugate.

Keywords: Nanomaterials, zinc oxide, drug delivery system, toxicity.

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208 Biorecognizable Nanoparticles Based On Hyaluronic Acid/Poly(ε-Caprolactone) Block Copolymer

Authors: Jong Ho Hwang, Dae Hwan Kang, Young-IL Jeong

Abstract:

Since hyaluronic acid (HA) receptor such as CD44 is over-expressed at sites of cancer cells, HA can be used as a targeting vehicles for anti-cancer drugs. The aim of this study is to synthesize block copolymer composed of hyaluronic acid and poly(ε-caprolactone) (HAPCL) and to fabricate polymeric micelles for anticancer drug targeting against CD44 receptor of tumor cells. Chemical composition of HAPCL was confirmed using 1H NMR spectroscopy. Doxorubicin (DOX) was incorporated into polymeric micelles of HAPCL. The diameters of HAPHS polymeric micelles were changed around 80nm and have spherical shapes. Targeting potential was investigated using CD44-overexpressing. When DOX-incorporated polymeric micelles was added to KB cells, they revealed strong red fluorescence color while blocking of CD44 receptor by pretreatment of free HA resulted in reduced intensity, indicating that HAPCL polymeric micelles have targetability against CD44 receptor.

Keywords: Hyaluronic acid, CD44 receptor, biorecognizable nanoparticles, block copolymer.

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207 Surfactant-Free O/W-Emulsion as Drug Delivery System

Authors: M. Kumpugdee-Vollrath, J.-P. Krause, S. Bürk

Abstract:

Most of the drugs used for pharmaceutical purposes are poorly water-soluble drugs. About 40% of all newly discovered drugs are lipophilic and the numbers of lipophilic drugs seem to increase more and more. Drug delivery systems such as nanoparticles, micelles or liposomes are applied to improve their solubility and thus their bioavailability. Besides various techniques of solubilization, oil-in-water emulsions are often used to incorporate lipophilic drugs into the oil phase. To stabilize emulsions surface active substances (surfactants) are generally used. An alternative method to avoid the application of surfactants was of great interest. One possibility is to develop O/W-emulsion without any addition of surface active agents or the so called “surfactant-free emulsion or SFE”. The aim of this study was to develop and characterize SFE as a drug carrier by varying the production conditions. Lidocaine base was used as a model drug. The injection method was developed. Effects of ultrasound as well as of temperature on the properties of the emulsion were studied. Particle sizes and release were determined. The long-term stability up to 30 days was performed. The results showed that the surfactant-free O/W emulsions with pharmaceutical oil as drug carrier can be produced.

Keywords: Emulsion, lidocaine, Miglyol, size, surfactant, light scattering, release, injection, ultrasound, stability.

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206 Evaluation of the Microscopic-Observation Drug-Susceptibility Assay Drugs Concentration for Detection of Multidrug-Resistant Tuberculosis

Authors: Anita, Sari Septiani Tangke, Rusdina Bte Ladju, Nasrum Massi

Abstract:

New diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. The microscopic-observation drug-susceptibility (MODS) assay is a rapid, accurate and simple liquid culture method to detect multidrug-resistant tuberculosis (MDR-TB). MODS were evaluated to determine a lower and same concentration of isoniazid and rifampin for detection of MDR-TB. Direct drug-susceptibility testing was performed with the use of the MODS assay. Drug-sensitive control strains were tested daily. The drug concentrations that used for both isoniazid and rifampin were at the same concentration: 0.16, 0.08 and 0.04μg per milliliter. We tested 56 M. tuberculosis clinical isolates and the control strains M. tuberculosis H37RV. All concentration showed same result. Of 53 M. tuberculosis clinical isolates, 14 were MDR-TB, 38 were susceptible with isoniazid and rifampin, 1 was resistant with isoniazid only. Drug-susceptibility testing was performed with the use of the proportion method using Mycobacteria Growth Indicator Tube (MGIT) system as reference. The result of MODS assay using lower concentration was significance (P<0.001) compare with the reference methods.

A lower and same concentration of isoniazid and rifampin can be used to detect MDR-TB. Operational cost and application can be more efficient and easier in resource-limited environments. However, additional studies evaluating the MODS using lower and same concentration of isoniazid and rifampin must be conducted with a larger number of clinical isolates.

Keywords: Isoniazid, MODS assay, MDR-TB, Rifampin.

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205 Biodegradable Surfactants for Advanced Drug Delivery Strategies

Authors: C. Hönnscheidt, R. Krull

Abstract:

Oxidative stress makes up common incidents in eukaryotic metabolism. The presence of diverse components disturbing the equilibrium during oxygen metabolism increases oxidative damage unspecifically in living cells. Body´s own ubiquinone (Q10) seems to be a promising drug in defending the heightened appearance of reactive oxygen species (ROS). Though, its lipophilic properties require a new strategy in drug formulation to overcome their low bioavailability. Consequently, the manufacture of heterogeneous nanodispersions is in focus for medical applications. The composition of conventional nanodispersions is made up of a drug-consisting core and a surfactive agent, also named as surfactant. Long-termed encapsulation of the surfactive components into tissues might be the consequence of the use during medical therapeutics. The potential of provoking side-effects is given by their nonbiodegradable properties. Further improvements during fabrication process use the incorporation of biodegradable components such as modified γ-polyglutamic acid which decreases the potential of prospective side-effects.

Keywords: Biopolymers, γ-Polyglutamic acid, Oxidative stress, Ubiquinone.

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204 Source of Oseltamivir Resistance Due to R152K Mutation of Influenza B Virus Neuraminidase: Molecular Modeling

Authors: J. Tengrang, T. Rungrotmongkol, S. Hannongbua

Abstract:

Every 2-3 years the influenza B virus serves epidemics. Neuraminidase (NA) is an important target for influenza drug design. Although, oseltamivir, an oral neuraminidase drug, has been shown good inhibitory efficiency against wild-type of influenza B virus, the lower susceptibility to the R152K mutation has been reported. Better understanding of oseltamivir efficiency and resistance toward the influenza B NA wild-type and R152K mutant, respectively, could be useful for rational drug design. Here, two complex systems of wild-type and R152K NAs with oseltamivir bound were studied using molecular dynamics (MD) simulations. Based on 5-ns MD simulation, the loss of notable hydrogen bond and decrease in per-residue decomposition energy from the mutated residue K152 contributed to drug compared to those of R152 in wildtype were found to be a primary source of high-level of oseltamivir resistance due to the R152K mutation.

Keywords: Influenza B neuraminidase, Molecular dynamics simulation, Oseltamivir resistance, R152K mutant

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203 Data Mining Classification Methods Applied in Drug Design

Authors: Mária Stachová, Lukáš Sobíšek

Abstract:

Data mining incorporates a group of statistical methods used to analyze a set of information, or a data set. It operates with models and algorithms, which are powerful tools with the great potential. They can help people to understand the patterns in certain chunk of information so it is obvious that the data mining tools have a wide area of applications. For example in the theoretical chemistry data mining tools can be used to predict moleculeproperties or improve computer-assisted drug design. Classification analysis is one of the major data mining methodologies. The aim of thecontribution is to create a classification model, which would be able to deal with a huge data set with high accuracy. For this purpose logistic regression, Bayesian logistic regression and random forest models were built using R software. TheBayesian logistic regression in Latent GOLD software was created as well. These classification methods belong to supervised learning methods. It was necessary to reduce data matrix dimension before construct models and thus the factor analysis (FA) was used. Those models were applied to predict the biological activity of molecules, potential new drug candidates.

Keywords: data mining, classification, drug design, QSAR

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202 Identifying a Drug Addict Person Using Artificial Neural Networks

Authors: Mustafa Al Sukar, Azzam Sleit, Abdullatif Abu-Dalhoum, Bassam Al-Kasasbeh

Abstract:

Use and abuse of drugs by teens is very common and can have dangerous consequences. The drugs contribute to physical and sexual aggression such as assault or rape. Some teenagers regularly use drugs to compensate for depression, anxiety or a lack of positive social skills. Teen resort to smoking should not be minimized because it can be "gateway drugs" for other drugs (marijuana, cocaine, hallucinogens, inhalants, and heroin). The combination of teenagers' curiosity, risk taking behavior, and social pressure make it very difficult to say no. This leads most teenagers to the questions: "Will it hurt to try once?" Nowadays, technological advances are changing our lives very rapidly and adding a lot of technologies that help us to track the risk of drug abuse such as smart phones, Wireless Sensor Networks (WSNs), Internet of Things (IoT), etc. This technique may help us to early discovery of drug abuse in order to prevent an aggravation of the influence of drugs on the abuser. In this paper, we have developed a Decision Support System (DSS) for detecting the drug abuse using Artificial Neural Network (ANN); we used a Multilayer Perceptron (MLP) feed-forward neural network in developing the system. The input layer includes 50 variables while the output layer contains one neuron which indicates whether the person is a drug addict. An iterative process is used to determine the number of hidden layers and the number of neurons in each one. We used multiple experiment models that have been completed with Log-Sigmoid transfer function. Particularly, 10-fold cross validation schemes are used to access the generalization of the proposed system. The experiment results have obtained 98.42% classification accuracy for correct diagnosis in our system. The data had been taken from 184 cases in Jordan according to a set of questions compiled from Specialists, and data have been obtained through the families of drug abusers.

Keywords: Artificial Neural Network, Decision Support System, drug abuse, drug addiction, Multilayer Perceptron.

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201 The Antibacterial and Anticancer Activity of Marine Actinomycete Strain HP411 Isolated in the Northern Coast of Vietnam

Authors: Huyen T. Pham, Nhue P. Nguyen, Tien Q. Phi, Phuong T. Dang, Hy G. Le

Abstract:

Since the marine environmental conditions are extremely different from the other ones, marine actinomycetes might produce novel bioactive compounds. Therefore, actinomycete strains were screened from marine water and sediment samples collected from the coastal areas of Northern Vietnam. Ninety-nine actinomycete strains were obtained on starch-casein agar media by dilution technique, only seven strains, named HP112, HP12, HP411, HPN11, HP 11, HPT13 and HPX12, showed significant antibacterial activity against both gram-positive and gram-negative bacteria (Bacillus subtilis ATCC 6633, Staphylococcus epidemidis ATCC 12228, Escherichia coli ATCC 11105). Further studies were carried out with the most active HP411 strain against Candida albicans ATCC 10231. This strain could grow rapidly on starch casein agar and other media with high salt containing 7-10% NaCl at 28-30oC. Spore-chain of HP411 showed an elongated and circular shape with 10 to 30 spores/chain. Identification of the strain was carried out by employing the taxonomical studies including the 16S rRNA sequence. Based on phylogenetic and phenotypic evidence it is proposed that HP411 to be belongs to species Streptomyces variabilis. The potent of the crude extract of fermentation broth of HP411 that are effective against wide range of pathogens: both grampositive, gram-negative and fungi. Further studies revealed that the crude extract HP411 could obtain the anticancer activity for cancer cell lines: Hep-G2 (liver cancer cell line); RD (cardiac and skeletal muscle letters cell line); FL (membrane of the uterus cancer cell line). However, the actinomycetes from marine ecosystem will be useful for the discovery of new drugs in the future.

Keywords: Marine actinomycetes, antibacterial, anticancer, Streptomyces variabilis.

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200 Pharmaceutical Microencapsulation Technology for Development of Controlled Release Drug Delivery systems

Authors: Mahmood Ahmad, Asadullah Madni, Muhammad Usman, Abubakar Munir, Naveed Akhtar, Haji M. Shoaib Khan

Abstract:

This article demonstrated development of controlled release system of an NSAID drug, Diclofenac sodium employing different ratios of Ethyl cellulose. Diclofenac sodium and ethyl cellulose in different proportions were processed by microencapsulation based on phase separation technique to formulate microcapsules. The prepared microcapsules were then compressed into tablets to obtain controlled release oral formulations. In-vitro evaluation was performed by dissolution test of each preparation was conducted in 900 ml of phosphate buffer solution of pH 7.2 maintained at 37 ± 0.5 °C and stirred at 50 rpm. At predetermined time intervals (0, 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 20 and 24 hrs). The drug concentration in the collected samples was determined by UV spectrophotometer at 276 nm. The physical characteristics of diclofenac sodium microcapsules were according to accepted range. These were off-white, free flowing and spherical in shape. The release profile of diclofenac sodium from microcapsules was found to be directly proportional to the proportion of ethylcellulose and coat thickness. The in-vitro release pattern showed that with ratio of 1:1 and 1:2 (drug: polymer), the percentage release of drug at first hour was 16.91 and 11.52 %, respectively as compared to 1:3 which is only 6.87 % with in this time. The release mechanism followed higuchi model for its release pattern. Tablet Formulation (F2) of present study was found comparable in release profile the marketed brand Phlogin-SR, microcapsules showed an extended release beyond 24 h. Further, a good correlation was found between drug release and proportion of ethylcellulose in the microcapsules. Microencapsulation based on coacervation found as good technique to control release of diclofenac sodium for making the controlled release formulations.

Keywords: Diclofenac sodium, Microencapsulationtechnology, Ethylcellulose, In-Vitro Release Profile

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199 Using Data Mining Techniques for Finding Cardiac Outlier Patients

Authors: Farhan Ismaeel Dakheel, Raoof Smko, K. Negrat, Abdelsalam Almarimi

Abstract:

In this paper we used data mining techniques to identify outlier patients who are using large amount of drugs over a long period of time. Any healthcare or health insurance system should deal with the quantities of drugs utilized by chronic diseases patients. In Kingdom of Bahrain, about 20% of health budget is spent on medications. For the managers of healthcare systems, there is no enough information about the ways of drug utilization by chronic diseases patients, is there any misuse or is there outliers patients. In this work, which has been done in cooperation with information department in the Bahrain Defence Force hospital; we select the data for Cardiac patients in the period starting from 1/1/2008 to December 31/12/2008 to be the data for the model in this paper. We used three techniques for finding the drug utilization for cardiac patients. First we applied a clustering technique, followed by measuring of clustering validity, and finally we applied a decision tree as classification algorithm. The clustering results is divided into three clusters according to the drug utilization, for 1603 patients, who received 15,806 prescriptions during this period can be partitioned into three groups, where 23 patients (2.59%) who received 1316 prescriptions (8.32%) are classified to be outliers. The classification algorithm shows that the use of average drug utilization and the age, and the gender of the patient can be considered to be the main predictive factors in the induced model.

Keywords: Data Mining, Clustering, Classification, Drug Utilization..

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198 Extended Release System of Hypoglycemic Agent Containing Solid Dispersions: Strategies and Mechanisms

Authors: Amit Kumar, Ramendeep Grawal, Peeyush Sharma, Dinesh Puri, Anil Bhandari

Abstract:

The main perspective of the present study aims at overcoming solubility problems by using the technique of solid dispersion. Repaglinide is a BCS Class II drug, having low aqueous solubility and therefore, low bioavailability. Solid dispersions of repaglinide with different carriers Polyvinyl Pyrrolidone (PVP) and Ethyl Cellulose (EC) in different ratios were prepared by suspending method and Dissolving methods. In vitro release studies revealed that the F7 formulation showed extended drug release. So, the dissolution profile of solid dispersion containing EC and PVP K30 (1: 3) was selected as the best formulation because of its extended drug release among all formulations. In conclusion, solid dispersions of Repaglinide in PVP have shown to be a promising approach to improve the bioavailability of Repaglinide.

Keywords: Ethyl Cellulose, Glibenclamide, Polyvinyl Pyrrolidone, Repaglinide, Solid Dispersion.

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197 Effect of Polyvinyl Pyrrolidone and Ethyl Cellulose Concentration on Release Profile and Kinetics of Glibenclamide Extended Release Dosage Form System

Authors: Amit Kumar, Peeyush Sharma, Anil Bhandari

Abstract:

The aim of present work was to optimize the effect of Ethyl Cellulose (EC) and Polyvinyl Pyrrolidone (PVP) concentration in extended release solid dispersion of Glibenclamide using combination of hydrophilic and hydrophobic polymers such as Polyvinyl Pyrrolidone and Ethyl cellulose. The advantage of solid dispersion technique provides a unique approach to particle size reduction and increased rates of dissolution. The compatibility studies of the drug and polymers were studied by TLC and results suggested no interaction between drug and polymers. Solid dispersions of Glibenclamide were prepared by common solvent evaporation method using Polyvinyl Pyrrolidone and Ethyl cellulose. The results indicated that homogeneous or heterogeneous conditions during the preparation methods employed governed the internal structures of the polymer matrices while retaining the drug in an amorphous form. F2 formulation prepared by solid dispersion method, displayed extended drug release followed by Higuchi matrix model indicating diffusion release of GLB from polymer matrices.

Keywords: Ethyl Cellulose, Glibenclamide, Polyvinyl Pyrrolidone, Solid Dispersion.

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196 Computer Modeling of Drug Distribution after Intravitreal Administration

Authors: N. Haghjou, M. J. Abdekhodaie, Y. L. Cheng, M. Saadatmand

Abstract:

Intravitreal injection (IVI) is the most common treatment for eye posterior segment diseases such as endopthalmitis, retinitis, age-related macular degeneration, diabetic retinopathy, uveitis, and retinal detachment. Most of the drugs used to treat vitreoretinal diseases, have a narrow concentration range in which they are effective, and may be toxic at higher concentrations. Therefore, it is critical to know the drug distribution within the eye following intravitreal injection. Having knowledge of drug distribution, ophthalmologists can decide on drug injection frequency while minimizing damage to tissues. The goal of this study was to develop a computer model to predict intraocular concentrations and pharmacokinetics of intravitreally injected drugs. A finite volume model was created to predict distribution of two drugs with different physiochemical properties in the rabbit eye. The model parameters were obtained from literature review. To validate this numeric model, the in vivo data of spatial concentration profile from the lens to the retina were compared with the numeric data. The difference was less than 5% between the numerical and experimental data. This validation provides strong support for the numerical methodology and associated assumptions of the current study.

Keywords: Posterior segment, Intravitreal injection (IVI), Pharmacokinetic, Modelling, Finite volume method.

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195 The Effect of Drug Prevention Programme Based On Cognitive-Behavioral Therapy (Cbt) and Multidimensional Self Concept Module towards Resiliency and Aggression among At-Risk Youth in Malaysia

Authors: Mohammad Aziz Shah Mohamed Arip, Aslina Ahmad, Fauziah Mohd Sa'ad, Samsiah Mohd Jais, Syed Sofian Syed Salim

Abstract:

This experimental study evaluates the effect of using Cognitive-Behavioral Therapy (CBT) and Multidimensional Self- Concept Model (MSCM) in a drug prevention programme to increase resiliency and reduce aggression among at-risk youth in Malaysia. A number of 60 (N=60) university students who were at-risk of taking drugs were involved in this study. Participants were identified with self-rating scales, Adolescent Resilience Attitude Scale (ARAS) and Aggression Questionnaire. Based on the mean score of these instruments, the participants were divided into the treatment group, and the control group. Data were analyzed using t-test. The finding showed that the mean score of resiliency was increased in the treatment group compared to the control group. It also shows that the mean score of aggression was reduced in the treatment group compared to the control group. Drug Prevention Programme was found to help in enhancing resiliency and reducing aggression among participants in the treatment group compared to the controlled group. Implications were given regarding the preventive actions on drug abuse among youth in Malaysia.

Keywords: Drug Prevention Programme, Cognitive-Behavioral Therapy (CBT), Multidimensional Self Concept Model (MSCM), resiliency, aggression, at-risk youth.

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194 An in Silico Approach for Prioritizing Drug Targets in Metabolic Pathway of Mycobacterium Tuberculosis

Authors: Baharak Khoshkholgh-Sima, Soroush Sardari, Jalal Izadi Mobarakeh, Ramezan Ali Khavari-Nejad

Abstract:

There is an urgent need to develop novel Mycobacterium tuberculosis (Mtb) drugs that are active against drug resistant bacteria but, more importantly, kill persistent bacteria. Our study structured based on integrated analysis of metabolic pathways, small molecule screening and similarity Search in PubChem Database. Metabolic analysis approaches based on Unified weighted used for potent target selection. Our results suggest that pantothenate synthetase (panC) and and 3-methyl-2-oxobutanoate hydroxymethyl transferase (panB) as a appropriate drug targets. In our study, we used pantothenate synthetase because of existence inhibitors. We have reported the discovery of new antitubercular compounds through ligand based approaches using computational tools.

Keywords: In Silico, Ligand-based Virtual Screening, Metabolic Pathways, Mycobacterium tuberculosis

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193 Hepatoprotective Effect of Oleuropein against Cisplatin-Induced Liver Damage in Rat

Authors: Salim Cerig, Fatime Geyikoglu, Murat Bakir, Suat Colak, Merve Sonmez, Kubra Koc

Abstract:

Cisplatin (CIS) is one of the most effective an anticancer drug and also toxic to cells by activating oxidative stress. Oleuropein (OLE) has key role against oxidative stress in mammalian cells, but the role of this antioxidant in the toxicity of CIS remains unknown. The aim of the present study was to investigate the efficacy of OLE on CIS-induced liver damages in male rats. With this aim, male Sprague Dawley rats were randomly assigned to one of eight groups: Control group; the group treated with 7 mg/kg/day CIS; the groups treated with 50, 100 and 200 mg/kg/day OLE (i.p.); and the groups treated with OLE for three days starting at 24 h following CIS injection. After 4 days of injections, serum was provided to assess the blood AST, ALT and LDH values. The liver tissues were removed for histological, biochemical (TAC, TOS and MDA) and genotoxic evaluations. In the CIS treated group, the whole liver tissue showed significant histological changes. Also, CIS significantly increased both the incidence of oxidative stress and the induction of 8-hydroxy-deoxyguanosine (8-OH-dG). Moreover, the rats taking CIS have abnormal results on liver function tests. However, these parameters reached to the normal range after administration of OLE for 3 days. Finally, OLE demonstrated an acceptable high potential and was effective in attenuating CIS-induced liver injury. In this trial, the 200 mg/kg dose of OLE firstly appeared to induce the most optimal protective response.

Keywords: Antioxidant response, cisplatin, histology, liver, oleuropein, 8-OhdG.

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192 Sexual Behaviors and Condom Attitude among Injecting Drug Users in Hai Phong, Vietnam: Qualitative Findings

Authors: Tanvir Ahmed, Thanh N. Long, Phan T. Huong, Donald E. Stewart

Abstract:

This paper presents views on condom use and the contexts of safe and unsafe sexual practices with different sexual partners and their relationships among Injecting Drug Users (IDUs) in Hai Phong, Vietnam. Fifteen IDUs participated and two local interviewers conducted qualitative semi-structured face-to-face interviews in September-October, 2012 in Vietnamese language. Data were analyzed thematically. Non-protective condom attitudes include negotiate or convince Female Sex Workers (FSW); not realizing risk, importance or necessity; partner doesn’t like, and having extra money/drug from clients. On the other hand, self-awareness, family-consciousness, suspicion of STI presence, fear of getting HIV, and client negotiation sometimes resulted in a safe-sex practice. A thematic diagram was developed to present the relationship (strong/weak) between condom attitude and sexual practice (safe/unsafe) by partner types. The experiences and views reflected in the qualitative information emphasize the heightened need for safe-sex education especially among young IDUs (male/female) highlighting sexual transmission risk.

Keywords: AIDS, HIV, injecting drug user, risk behaviors, Vietnam.

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191 A Recommendation to Oncologists for Cancer Treatment by Immunotherapy: Quantitative and Qualitative Analysis

Authors: Mandana Kariminejad, Ali Ghaffari

Abstract:

Today, the treatment of cancer, in a relatively short period, with minimum adverse effects is a great concern for oncologists. In this paper, based on a recently used mathematical model for cancer, a guideline has been proposed for the amount and duration of drug doses for cancer treatment by immunotherapy. Dynamically speaking, the mathematical ordinary differential equation (ODE) model of cancer has different equilibrium points; one of them is unstable, which is called the no tumor equilibrium point. In this paper, based on the number of tumor cells an intelligent soft computing controller (a combination of fuzzy logic controller and genetic algorithm), decides regarding the amount and duration of drug doses, to eliminate the tumor cells and stabilize the unstable point in a relatively short time. Two different immunotherapy approaches; active and adoptive, have been studied and presented. It is shown that the rate of decay of tumor cells is faster and the doses of drug are lower in comparison with the result of some other literatures. It is also shown that the period of treatment and the doses of drug in adoptive immunotherapy are significantly less than the active method. A recommendation to oncologists has also been presented.

Keywords: Tumor, immunotherapy, fuzzy controller, Genetic algorithm, mathematical model.

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190 Phage Capsid for Efficient Delivery of Cytotoxic Drugs

Authors: Simona Dostalova, Ana Maria Jimenez Jimenez, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

Abstract:

Various nanomaterials can be used as a drug delivery vehicles in nanomedicine, called nanocarriers. They can either be organic or inorganic, synthetic or natural-based. Although synthetic nanocarriers are easier to produce, they can often be toxic for the organism and thus not suitable for use in treatment. From naturalbased nanocarriers, the most commonly used are protein cages or viral capsids. In this work, virus bacteriophage λ was used for delivery of different cytotoxic drugs (cisplatin, carboplatin, oxaliplatin and doxorubicin). Large quantities of phage λ were obtained from phage λ-producing strain of E. coli cultivated in medium with 0.2% maltose. After killing of E. coli with chloroform and its removal by centrifugation, the phage was concentrated by ultracentrifugation at 130 000×g and 4°C for 3 h. The encapsulation of the drugs was performed by infusion method and four different concentrations of the drugs were encapsulated (200; 100; 50; 25 μg·mL-1). Free drug molecules were removed by filtration. The encapsulation was verified using the absorbance for doxorubicin and atomic absorption spectrometry for platinum cytostatics. The amount of encapsulated drug linearly increased with the increasing concentration of applied drug with the determination coefficient R2=0.989 for doxorubicin; R2=0.967 for cisplatin; R2=0.989 for carboplatin and R2=0.996 for oxaliplatin. The overall encapsulation efficiency was calculated as 50% for doxorubicin; 8% for cisplatin; 6% for carboplatin and 10% for oxaliplatin.

Keywords: Bacteriophage λ, doxorubicin, platinum cytostatics, protein-based nanocarrier, viral capsid.

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189 Development and Optimization of Colon Targeted Drug Delivery System of Ayurvedic Churna Formulation Using Eudragit L100 and Ethyl Cellulose as Coating Material

Authors: Anil Bhandari, Imran Khan Pathan, Peeyush K. Sharma, Rakesh K. Patel, Suresh Purohit

Abstract:

The purpose of this study was to prepare time and pH dependent release tablets of Ayurvedic Churna formulation and evaluate their advantages as colon targeted drug delivery system. The Vidangadi Churna was selected for this study which contains Embelin and Gallic acid. Embelin is used in Helminthiasis as therapeutic agent. Embelin is insoluble in water and unstable in gastric environment so it was formulated in time and pH dependent tablets coated with combination of two polymers Eudragit L100 and ethyl cellulose. The 150mg of core tablet of dried extract and lactose were prepared by wet granulation method. The compression coating was used in the polymer concentration of 150mg for both the layer as upper and lower coating tablet was investigated. The results showed that no release was found in 0.1 N HCl and pH 6.8 phosphate buffers for initial 5 hours and about 98.97% of the drug was released in pH 7.4 phosphate buffer in total 17 Hours. The in vitro release profiles of drug from the formulation could be best expressed first order kinetics as highest linearity (r2= 0.9943). The results of the present study have demonstrated that the time and pH dependent tablets system is a promising vehicle for preventing rapid hydrolysis in gastric environment and improving oral bioavailability of Embelin and Gallic acid for treatment of Helminthiasis.

Keywords: Embelin, Gallic acid, Vidangadi Churna, Colon targeted drug delivery.

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188 Determinants of Profitability in Indian Pharmaceutical Firms in the New Intellectual Property Rights Regime

Authors: Shilpi Tyagi, D. K. Nauriyal

Abstract:

This study investigates the firm level determinants of profitability of Indian drug and pharmaceutical industry. The study uses inflation adjusted panel data for a period 2000-2013 and applies OLS regression model with Driscoll-Kraay standard errors. It has been found that export intensity, A&M intensity, firm’s market power and stronger patent regime dummy have exercised positive influence on profitability. The negative and statistically significant influence of R&D intensity and raw material import intensity points to the need for firms to adopt suitable investment strategies. The study suggests that firms are required to pay far more attention to optimize their operating expenditures, advertisement and marketing expenditures and improve their export orientation, as part of the long term strategy.

Keywords: Indian drug and pharmaceutical industry, trade related intellectual property rights, research and development, food and drug administration.

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187 Vincristine-Dextran Complex Loaded Solid Lipid Nanoparticles for Drug Delivery to the Brain

Authors: E. Aboutaleb, R. Dinarvand

Abstract:

The purpose of this work was to inspect the potential of vincristine-dextran complex loaded solid lipid nanoparticles for drug delivery to the brain. The nanoparticles were stained with a fluorescence dye and their plasma pharmacokinetic and brain concentrations were investigated following injection to rats. The result revealed a significant improvement in the plasma concentration profile of the SLN injected animals as well as a sharp increased concentration in the brains.

Keywords: Brain, Coumarin-6, Nanoparticles, SLN.

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186 Learners’ Violent Behaviour and Drug Abuse as Major Causes of Tobephobia in Schools

Authors: Prakash Singh

Abstract:

Many schools throughout the world are facing constant pressure to cope with the violence and drug abuse of learners who show little or no respect for acceptable and desirable social norms. These delinquent learners tend to harbour feelings of being beyond reproach because they strongly believe that it is well within their rights to engage in violent and destructive behaviour. Knives, guns, and other weapons appear to be more readily used by them on the school premises than before. It is known that learners smoke, drink alcohol, and use drugs during school hours, hence, their ability to concentrate, work, and learn, is affected. They become violent and display disruptive behaviour in their classrooms as well as on the school premises, and this atrocious behaviour makes it possible for drug dealers and gangsters to gain access onto the school premises. The primary purpose of this exploratory quantitative study was therefore to establish how tobephobia (TBP), caused by school violence and drug abuse, affects teaching and learning in schools. The findings of this study affirmed that poor discipline resulted in producing poor quality education. Most of the teachers in this study agreed that educating learners who consumed alcohol and other drugs on the school premises resulted in them suffering from TBP. These learners are frequently abusive and disrespectful, and resort to violence to seek attention. As a result, teachers feel extremely demotivated and suffer from high levels of anxiety and stress. The word TBP will surely be regarded as a blessing by many teachers throughout the world because finally, there is a word that will make people sit up and listen to their problems that cause real fear and anxiety in schools.

Keywords: Aims and objectives of quality education, Debilitating effects of tobephobia, Fear of failure associated with education, learners’ violent behaviour and drug abuse.

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185 Formulation and Evaluation of Niosomes Containing an Antihypertensive Drug

Authors: Sunil Kamboj, Suman Bala, Vipin Saini

Abstract:

Niosomes were formulated with an aim of enhancing the oral bioavailability of losartan potassium and formulated in different molar ratios of surfactant, cholesterol and dicetyl phosphate. The formulated niosomes were found in range of 54.98 µm to 107.85 µm in size. Formulations with 1:1 ratio of surfactant and cholesterol have shown maximum entrapment efficiencies. Niosomes with sorbitan monostearate showed maximum drug release and zero order release kinetics, at the end of 24 hours. The in vivo study has shown the significant enhancement in oral bioavailability of losartan potassium in rats, after a dose of 10 mg/kg. The average relative bioavailability in relation with pure drug solution was found 2.56, indicates more than two fold increase in oral bioavailability. A significant increment in MRT reflects the release retarding ability of the vesicles. In conclusion, niosomes could be a promising delivery of losartan potassium with improved oral bioavailability and prolonged release profiles.

Keywords: Non-ionic surfactant vesicles, losartan potassium, oral bioavailability, controlled release.

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184 Polymeric Sustained Biodegradable Patch Formulation for Wound Healing

Authors: Abhay Asthana, Gyati Shilakari Asthana

Abstract:

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

Keywords: Sustained biodegradation, wound healing, polymeric patch, stability.

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183 Molecular Dynamics Study on Laninamivir Inhibiting Neuraminidases of H5N1 and pH1N1 Influenza a Viruses

Authors: A. Meeprasert, W. Khuntawee, S. Hannongbua, T. Rungrotmongkol

Abstract:

Viral influenza A subtypes H5N1 and pandemic H1N1 (pH1N1) have worldwide emerged and transmitted. The most common anti-influenza drug for treatment of both seasonal and pandemic influenza viruses is oseltamivir that nowadays becomes resistance to influenza neuraminidase. The novel long-acting drug, laninamivir, was discovered for treatment of the patients infected with influenza B and influenza A viruses. In the present study, laninamivir complexed with wild-type strain of both H5N1 and pH1N1 viruses were comparatively determined the structures and drug-target interactions by means of molecular dynamics (MD) simulations. The results show that the hydrogen bonding interactions formed between laninamivir and its binding residues are likely similar for the two systems. Additionally, the presence of intermolecular interactions from laninamivir to the residues in the binding pocket is established through their side chains in accordance with hydrogen bond interactions.

Keywords: Laninamivir, neuraminidase, H5N1, pandemic H1N1, wild-type, MD simulation

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