Search results for: antibacterial drug

Authors: Ved Vrat Verma, Rani Gupta, Manisha Goel

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γ-glutamyltranspeptidase (GGT: EC 2.3.2.2) is an N-terminal nucleophile hydrolase conserved in all three domains of life. GGT plays a key role in glutathione metabolism where it catalyzes the breakage of the γ-glutamyl bonds and transfer of γ-glutamyl group to water (hydrolytic activity) or amino acids or short peptides (transpeptidase activity). GGTs from bacteria, archaea, and eukaryotes (human, rat and mouse) are homologous proteins sharing >50% sequence similarity and conserved four layered αββα sandwich like three dimensional structural fold. These proteins though similar in their structure to each other, are quite diverse in their enzyme activity: some GGTs are better at hydrolysis reactions but poor in transpeptidase activity, whereas many others may show opposite behaviour. GGT is known to be involved in various diseases like asthma, parkinson, arthritis, and gastric cancer. Its inhibition prior to chemotherapy treatments has been shown to sensitize tumours to the treatment. Microbial GGT is known to be a virulence factor too, important for the colonization of bacteria in host. However, all known inhibitors (mimics of its native substrate, glutamate) are highly toxic because they interfere with other enzyme pathways. However, a few successful efforts have been reported previously in designing species specific inhibitors. We aim to leverage the diversity seen in GGT family (pathogen vs. eukaryotes) for designing specific inhibitors. Thus, in the present study, we have used DIVERGE software to identify sites in GGT proteins, which are crucial for the functional and structural divergence of these proteins. Since, type II divergence sites vary in clade specific manner, so type II divergent sites were our focus of interest throughout the study. Type II divergent sites were identified for pathogen vs. eukaryotes clusters and sites were marked on clade specific representative structures HpGGT (2QM6) and HmGGT (4ZCG) of pathogen and eukaryotes clade respectively. The crucial divergent sites within 15 A radii of the binding cavity were highlighted, and in-silico mutations were performed on these sites to delineate the role of these sites on the mechanism of catalysis and protein folding. Further, the amino acid network (AAN) analysis was also performed by Cytoscape to delineate assortative mixing for cavity divergent sites which could strengthen our hypothesis. Additionally, molecular dynamics simulations were performed for wild complexes and mutant complexes close to physiological conditions (pH 7.0, 0.1 M ionic strength and 1 atm pressure) and the role of putative divergence sites and structural integrities of the homologous proteins have been analysed. The dynamics data were scrutinized in terms of RMSD, RMSF, non-native H-bonds and salt bridges. The RMSD, RMSF fluctuations of proteins complexes are compared, and the changes at protein ligand binding sites were highlighted. The outcomes of our study highlighted some crucial divergent sites which could be used for novel inhibitors designing in a species-specific manner. Since, for drug development, it is challenging to design novel drug by targeting similar protein which exists in eukaryotes, so this study could set up an initial platform to overcome this challenge and help to deduce the more effective targets for novel drug discovery.

Keywords: γ-glutamyltranspeptidase, divergence, species-specific, drug design

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Authors: Gajanan M. Sonwane

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The computational studies on 2-phenazinamines with their protein targets have been carried out to design compounds with potential anticancer activity. This strategy of designing compounds possessing selectivity over specific tyrosine kinase has been achieved through G-QSAR and molecular docking studies. The objective of this research has been to design newer 2-phenazinamine derivatives as Bcr-Abl tyrosine kinase inhibitors by G-QSAR, molecular docking studies followed by wet-lab studies along with evaluation of their anticancer potential. Computational chemistry was done by using VLife MDS 4.3 and Autodock 4.2 followed by wet-lab experiments for synthesizing 2-phenazinamine derivatives. The chemical structures of ligands in 2D were drawn by employing Chemdraw 2D Ultra 8.0 and were converted into 3D. These were optimized by using a semi-empirical method called MOPAC. The protein structure was retrieved from RCSC protein data bank as a PDB file. The binding interactions of protein and ligands were done by using PYMOL. The molecular properties of the designed compounds were predicted in silico by using Osiris property explorer. The parent compound 2-phenazinamine was synthesized by reduction of 2, 4-dinitro-N-phenyl-benzenamine in the presence of tin chloride followed by cyclization in the presence of nitrobenzene and magnesium sulfate. The derivatization at the amino function of 2-phenazinamine was performed by treating parent compound with various aldehydes in the presence of dicyclohexylcarbodiimide (DCC) and urea to afford 2-(2-chlorophenyl)-3-(phenazine-2-yl) thiazolidine-4-one. Synthesized 39 novel derivatives of 2-phenazinamine and performed antioxidant activity, anti antiproliferative on the bulb of onion and anticancer activity on cell line showing significant competition with marked blockbuster drug imatinib.

Keywords: computer-aided drug design, tyrosin kinases, anticancer, docking

Procedia PDF Downloads 129

Authors: Saman Ahani, Aboozar Dehghan, Roham Vali, Hamid Salehian, Amin Ebrahimi

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Pulsed-wave (PW) doppler ultrasonography is a non-invasive, relatively accurate imaging technique that can measure blood speed. The imaging could be obtained via the common carotid artery, as one of the main vessels supplying the blood of vital organs. In horses, factors such as susceptibility to depression of the cardiovascular system and their large muscular mass have rendered them vulnerable to changes in blood speed. One of the most important factors causing blood velocity changes is the administration of anesthetic drugs, including Ketamine and Acepromazine. Thus, in this study, the Pulsed-wave doppler technique was performed to assess the highest blood velocity in the common carotid artery following administration of Ketamine and Acepromazine. Six male and six female healthy Kurdish horses weighing 351 ± 46 kg (mean ± SD) and aged 9.2 ± 1.7 years (mean ± SD) were housed under animal welfare guidelines. After fasting for six hours, the normal blood flow velocity in the common carotid artery was measured using a Pulsed-wave doppler ultrasonography machine (BK Medical, Denmark), and a high-frequency linear transducer (12 MHz) without applying any sedative drugs as a control group. The same procedure was repeated after each individual received the following medications: 1.1, 2.2 mg/kg Ketamine (Pfizer, USA), and 0.5, 1 mg/kg Acepromizine (RACEHORSE MEDS, Ukraine), with an interval of 21 days between the administration of each dose and/or drug. The ultrasonographic study was done five (T5) and fifteen (T15) minutes after injecting each dose intravenously. Lastly, the statistical analysis was performed using SPSS software version 22 for Windows and a P value less than 0.05 was considered to be statistically significant. Five minutes after administration of Ketamine (1.1, 2.2 mg/kg) in both male and female horses, the blood velocity decreased to 38.44, 34.53 cm/s in males, and 39.06, 34.10 cm/s in females in comparison to the control group (39.59 and 40.39 cm/s in males and females respectively) while administration of 0.5 mg/kg Acepromazine led to a significant rise (73.15 and 55.80 cm/s in males and females respectively) (p<0.05). It means that the most drastic change in blood velocity, regardless of gender, refers to the latter dose/drug. In both medications and both genders, the increase in doses led to a decrease in blood velocity compared to the lower dose of the same drug. In all experiments in this study, the blood velocity approached its normal value at T15. In another study comparing the blood velocity changes affected by Ketamine and Acepromazine through femoral arteries, the most drastic changes were attributed to Ketamine; however, in this experiment, the maximum blood velocity was observed following administration of Acepromazine via the common carotid artery. Therefore, further experiments using the same medications are suggested using Pulsed-wave doppler measuring the blood velocity changes in both femoral and common carotid arteries simultaneously.

Keywords: Acepromazine, common carotid artery, horse, ketamine, pulsed-wave doppler ultrasonography

Procedia PDF Downloads 118

Authors: Sreeparna Majee, G. C. Shit

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A study on targeted drug delivery is carried out in an unsteady flow of blood infused with magnetic NPs (nanoparticles) with an aim to understand the flow pattern and nanoparticle aggregation in a diseased arterial segment having stenosis. The magnetic NPs are supervised by the magnetic field which is significant for therapeutic treatment of arterial diseases, tumor and cancer cells and removing blood clots. Coupled thermal energy have also been analyzed by considering dissipation of energy because of the application of the magnetic field and the viscosity of blood. Simulation technique used to solve the mathematical model is vorticity-stream function formulations in the diseased artery. An elevation in SLP (Specific loss power) is noted in the aortic bloodstream when the agglomeration of nanoparticles is higher. This phenomenon has potential application in the treatment of hyperthermia. The study focuses on the lowering of WSS (Wall Shear Stress) with increasing particle concentration at the downstream of the stenosis which depicts the vigorous flow circulation zone. These low shear stress regions prolong the residing time of the nanoparticles carrying drugs which soaks up the LDL (Low Density Lipoprotein) deposition. Moreover, an increase in NP concentration enhances the Nusselt number which marks the increase of heat transfer from the arterial wall to the surrounding tissues to destroy tumor and cancer cells without affecting the healthy cells. The results have a significant influence in the study of medicine, to treat arterial diseases such as atherosclerosis without the need for surgery which can minimize the expenditures on cardiovascular treatments.

Keywords: magnetic nanoparticles, blood flow, atherosclerosis, hyperthermia

Procedia PDF Downloads 132

Authors: V. Bezverbny

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The actuality of the project deals with stable growing of deviant behavior’ statistics among Moscow citizens. During the recent years the socioeconomic health, wealth and life expectation of Moscow residents is regularly growing up, but the limits of crime and drug addiction have grown up seriously. Another serious Moscow problem has been economical stratification of population. The cost of identical residential areas differs at 2.5 times. The project is aimed at complex research and the development of methodology for main factors and reasons evaluation of deviant behavior growing in Moscow. The main project objective is finding out the links between the urban environment quality and dynamics of citizens’ deviant behavior in regional and municipal aspect using the statistical research methods and GIS modeling. The conducted research allowed: 1) to evaluate the dynamics of deviant behavior in Moscow different administrative districts; 2) to describe the reasons of crime increasing, drugs addiction, alcoholism, suicides tendencies among the city population; 3) to develop the city districts classification based on the level of the crime rate; 4) to create the statistical database containing the main indicators of Moscow population deviant behavior in 2010-2015 including information regarding crime level, alcoholism, drug addiction, suicides; 5) to present statistical indicators that characterize the dynamics of Moscow population deviant behavior in condition of expanding the city territory; 6) to analyze the main sociological theories and factors of deviant behavior for concretization the deviation types; 7) to consider the main theoretical statements of the city sociology devoted to the reasons for deviant behavior in megalopolis conditions. To explore the level of deviant behavior’ factors differentiation, the questionnaire was worked out, and sociological survey involved more than 1000 people from different districts of the city was conducted. Sociological survey allowed to study the socio-economical and psychological factors of deviant behavior. It also included the Moscow residents’ open-ended answers regarding the most actual problems in their districts and reasons of wish to leave their place. The results of sociological survey lead to the conclusion that the main factors of deviant behavior in Moscow are high level of social inequality, large number of illegal migrants and bums, nearness of large transport hubs and stations on the territory, ineffective work of police, alcohol availability and drug accessibility, low level of psychological comfort for Moscow citizens, large number of building projects.

Keywords: deviant behavior, megapolis, Moscow, urban environment, social stratification

Procedia PDF Downloads 187

Authors: Mohsen Shati, Seyede Salehe Mortazavi, Seyed Kazem Malakouti, Hamidreza Khanke Fazlollah Ahmadi

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Taking unnecessary or excessive medication or using drugs with no indication (polypharmacy) by people of all ages, especially the elderly, is associated with increased adverse drug reactions (ADR), medical errors, hospitalization and escalating the costs. It may be facilitated or impeded by the healthcare system. In this study, we are going to describe the role of the health system in the practice of polypharmacy in Iranian elderly. In this Inductive qualitative content analysis using Graneheim and Lundman methods, purposeful sample selection until saturation has been made. Participants have been selected from doctors, pharmacists, policy-makers and the elderly. A total of 25 persons (9 men and 16 women) have participated in this study. Data analysis after incorporating codes with similar characteristics revealed 14 subcategories and six main categories of the referral system, physicians’ accessibility, health data management, drug market, laws enforcement, and social protection. Some of the conditions of the healthcare system have given rise to polypharmacy in the elderly. In the absence of a comprehensive specialty and subspecialty referral system, patients may go to any physician office so may well be confused about numerous doctors' prescriptions. Electronic records not being prepared for the patients, failure to comply with laws, lack of robust enforcement for the existing laws and close surveillance are among the contributing factors. Inadequate insurance and supportive services are also evident. Age-specific care providing has not yet been institutionalized, while, inadequate specialist workforce playing a major role. So, one may not ignore the health system as contributing factor in designing effective interventions to fix the problem.

Keywords: elderly, polypharmacy, health system, qualitative study

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Authors: Nisa Mohan

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Adverse drug event (ADE) related hospital admissions are common among older people. The first step in prevention is accurately estimating the prevalence of ADE admissions. Clinical coding is an efficient method to estimate the prevalence of ADE admissions. The objective of the study is to estimate the rate of under-coding of ADE admissions in older people in New Zealand and to explore how clinical coders decide whether or not to code an admission as an ADE. There has not been any research in New Zealand to explore these areas. This study is done using a mixed-methods approach. Two common and serious ADEs in older people, namely bleeding and hypoglycaemia were selected for the study. In study 1, eight hundred medical records of people aged 65 years and above who are admitted to hospital due to bleeding and hypoglycemia during the years 2015 – 2016 were selected for quantitative retrospective medical records review. This selection was made to estimate the proportion of ADE-related bleeding and hypoglycemia admissions that are not coded as ADEs. These files were reviewed and recorded as to whether the admission was caused by an ADE. The hospital discharge data were reviewed to check whether all the ADE admissions identified in the records review were coded as ADEs, and the proportion of under-coding of ADE admissions was estimated. In study 2, thirteen clinical coders were selected to conduct qualitative semi-structured interviews using a general inductive approach. Participants were selected purposively based on their experience in clinical coding. Interview questions were designed in a way to investigate the reasons for the under-coding of ADE admissions. The records review study showed that 35% (Cl 28% - 44%) of the ADE-related bleeding admissions and 22% of the ADE-related hypoglycemia admissions were not coded as ADEs. Although the quality of clinical coding is high across New Zealand, a substantial proportion of ADE admissions were under-coded. This shows that clinical coding might under-estimate the actual prevalence of ADE related hospital admissions in New Zealand. The interviews with the clinical coders added that lack of time for searching for information to confirm an ADE admission, inadequate communication with clinicians, along with coders’ belief that an ADE is a small thing might be the potential reasons for the under-coding of the ADE admissions. This study urges the coding policymakers, auditors, and trainers to engage with the unconscious cognitive biases and short-cuts of the clinical coders. These results highlight that further work is needed on interventions to improve the clinical coding of ADE admissions, such as providing education to coders about the importance of ADEs, education to clinicians about the importance of clear and confirmed medical records entries, availing pharmacist service to improve the detection and clear documentation of ADE admissions and including a mandatory field in the discharge summary about external causes of diseases.

Keywords: adverse drug events, bleeding, clinical coders, clinical coding, hypoglycemia

Procedia PDF Downloads 122

Authors: Haykal. Kay-Anne

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The health and well-being of students is a priority for the Faculty of Medicine at the University of Ottawa. The demands of medical studies are extreme, and many studies confirm that the prevalence of psychological distress is very high among medical students and that it is higher than that of the general population of the same age. The main goal is to identify risk factors for mental health among medical students at the University of Ottawa. The secondary objectives are to determine the variation of these risk factors according to demographic variables, as well as to determine if there is a change in the mental health of students during the 1st and 3rd years of their study. Medical students have a mandatory first and third-year wellness check meeting. This assessment includes a questionnaire on demographic information, mental health, and risk factors such as physical health, sleep, social support, financial stress, education and career, stress and drug use and/or alcohol. Student responses were converted to numerical values and analyzed statistically. The results show that 61% of the variation in the mean of the mental health score is explained by the following risk factors (R2 = 0.61, F (9.396) = 67.197, p < 0.01): lack of sleep and fatigue (β = 0.281, p < 0.001), lack of social support (β = 0.217, p <0.001), poor study or career development (β = 0.195, p < 0.001) and an increase stress and drug and alcohol use (β = -0.239, p < 0.001). No demographic variable has a significant effect on the presence of risk factors. In addition, fixed-effects regression demonstrated significantly lower mental health (p < 0.1) among first-year students (M = 0.587, SD = 0.072) than among third-year students (M = 0.719, SD = 0.071). This preliminary study indicates the need to continue data collection and analysis to increase the significance of the study results. As risk factors are present at the beginning of medical studies, it is important to offer resources to students very early in their medical studies and to have close monitoring and supervision.

Keywords: assessment of mental health, medical students, risk factors for mental health, wellness assessment

Procedia PDF Downloads 121

Authors: Soma Banerjee, Aamen Talukdar, Argha Mandal, Dipankar Chaudhuri

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Japanese Encephalitis is a major infectious disease with nearly half the world’s population living in areas where it is prevalent. Currently, treatment for it involves only supportive care and symptom management through vaccination. Due to the lack of antiviral drugs against Japanese Encephalitis Virus (JEV), the quest for such agents remains a priority. For these reasons, simulation studies of drug targets against JEV are important. Towards this purpose, docking experiments of the kinase inhibitors were done against the chosen target NS3 helicase as it is a nucleoside binding protein. Previous efforts regarding computational drug design against JEV revealed some lead molecules by virtual screening using public domain software. To be more specific and accurate regarding finding leads, in this study a proprietary software Schrödinger-GLIDE has been used. Druggability of the pockets in the NS3 helicase crystal structure was first calculated by SITEMAP. Then the sites were screened according to compatibility with ATP. The site which is most compatible with ATP was selected as target. Virtual screening was performed by acquiring ligands from databases: KinaseSARfari, KinaseKnowledgebase and Published inhibitor Set using GLIDE. The 25 ligands with best docking scores from each database were re-docked in XP mode. Protein structure alignment of NS3 was performed using VAST against MMDB, and similar human proteins were docked to all the best scoring ligands. The low scoring ligands were chosen for further studies and the high scoring ligands were screened. Seventy-three ligands were listed as the best scoring ones after performing HTVS. Protein structure alignment of NS3 revealed 3 human proteins with RMSD values lesser than 2Å. Docking results with these three proteins revealed the inhibitors that can interfere and inhibit human proteins. Those inhibitors were screened. Among the ones left, those with docking scores worse than a threshold value were also removed to get the final hits. Analysis of the docked complexes through 2D interaction diagrams revealed the amino acid residues that are essential for ligand binding within the active site. Interaction analysis will help to find a strongly interacting scaffold among the hits. This experiment yielded 21 hits with the best docking scores which could be investigated further for their drug like properties. Aside from getting suitable leads, specific NS3 helicase-inhibitor interactions were identified. Selection of Target modification strategies complementing docking methodologies which can result in choosing better lead compounds are in progress. Those enhanced leads can lead to better in vitro testing.

Keywords: antivirals, docking, glide, high-throughput virtual screening, Japanese encephalitis, ns3 helicase

Procedia PDF Downloads 222

Authors: Alex Kiselyov, Suehyun Cho, Darrell Harrington; Florent Cros, Olin Palmer, John Caputo, Michael Kardosh, Eran Oren, William Loudon, Michael Shpigelmacher

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Despite the most aggressive surgical and adjuvant therapeutic strategies, treatment of both pediatric and adult brainstem tumors remains problematic. Novel strategies, including targeted biologics, immunotherapy, and specialized delivery systems such as convection-enhanced delivery (CED), have been proposed. While some of these novel treatments are entering phase I trials, the field is still in need of treatment(s) that exhibits dramatically enhanced potency with optimal therapeutic ratio. Bionaut Labs has developed a modular microrobotic platform for performing localized delivery of diverse therapeutics in vivo. Our biocompatible particles (Bionauts™) are externally propelled and visualized in real-time. Bionauts™ are specifically designed to enhance the effect of radiation therapy via anatomically precise delivery of a radiosensitizing agent, as exemplified by temozolomide (TMZ) and Avastin™ to the brainstem gliomas of diverse origin. The treatment protocol is designed to furnish a better therapeutic outcome due to the localized (vs systemic) delivery of the drug to the neoplastic lesion(s) for use as a synergistic combination of radiation and radiosensitizing agent. In addition, the procedure is minimally invasive and is expected to be appropriate for both adult and pediatric patients. Current progress, including platform optimization, selection of the lead radiosensitizer as well as in vivo safety studies of the Bionauts™ in large animals, specifically the spine and the brain of porcine and ovine models, will be discussed.

Keywords: Bionaut, brainstem, glioma, local delivery, micro-robot, radiosensitizer

Procedia PDF Downloads 188

Authors: Mouna Baassi, Mohamed Moussaoui, Hatim Soufi, Sanchaita RajkhowaI, Ashwani Sharma, Subrata Sinha, Said Belaaouad

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Human Immunodeficiency Virus type 1 protease (HIV-1 PR) is one of the most challenging targets of antiretroviral therapy used in the treatment of AIDS-infected people. The performance of protease inhibitors (PIs) is limited by the development of protease mutations that can promote resistance to the treatment. The current study was carried out using statistics and bioinformatics tools. A series of thirty-three compounds with known enzymatic inhibitory activities against HIV-1 protease was used in this paper to build a mathematical model relating the structure to the biological activity. These compounds were designed by software; their descriptors were computed using various tools, such as Gaussian, Chem3D, ChemSketch and MarvinSketch. Computational methods generated the best model based on its statistical parameters. The model’s applicability domain (AD) was elaborated. Furthermore, one compound has been proposed as efficient against HIV-1 protease with comparable biological activity to the existing ones; this drug candidate was evaluated using ADMET properties and Lipinski’s rule. Molecular Docking performed on Wild Type and Mutant Type HIV-1 proteases allowed the investigation of the interaction types displayed between the proteases and the ligands, Darunavir (DRV) and the new drug (ND). Molecular dynamics simulation was also used in order to investigate the complexes’ stability, allowing a comparative study of the performance of both ligands (DRV & ND). Our study suggested that the new molecule showed comparable results to that of Darunavir and may be used for further experimental studies. Our study may also be used as a pipeline to search and design new potential inhibitors of HIV-1 proteases.

Keywords: QSAR, ADMET properties, molecular docking, molecular dynamics simulation.

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Authors: B. Sadek, N. Khan, Shreesh K. Ojha, Adel Sadeq, D. Lazewska, K. Kiec-Kononowicz

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The involvement of Histamine H3 receptors (H3Rs) in memory and the potential role of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer disease (AD) is well established. Therefore, the memory-enhancing effects of the H3R antagonist DL77 on MK801-induced cognitive deficits were evaluated in passive avoidance paradigm (PAP) and novel object recognition (NOR) tasks in adult male rats, applying donepezil (DOZ) as a reference drug. Animals pretreated with acute systemic administration of DL77 (2.5, 5, and 10 mg/kg, i.p.) were significantly ameliorated in regard to MK801-induced memory deficits in PAP. The ameliorative effect of most effective dose of DL77 (5 mg/kg, i.p.) was abrogated when animals were pretreated with a co-injection with the H3R agonist R-(α)-methylhistamine (RAMH, 10 mg/kg, i.p.). Moreover, and in the NOR paradigm, DL77 (5 mg/kg, i.p.) reversed MK801-induced deficits long-term memory (LTM), and the DL77-provided procognitive effect was comparable to that of reference drug DOZ, and was reversed when animals were co-injected with RAMH (10 mg/kg, i.p.). However, DL77(5 mg/kg, i.p.) failed to alter short-term memory (STM) impairment in NOR test. Furthermore, DL77 (5 mg/kg) failed to induce any alterations of anxiety and locomotor behaviors of animals naive to elevated-plus maze (EPM), indicating that the ameliorative effects observed in PAP or NOR tests were not associated to alterations in emotions or in natural locomotion of tested animals. These results reveal the potential contribution of H3Rs in modulating CNS neurotransmission systems associated with neurodegenerative disorders, e.g., AD.

Keywords: histamine H3 receptor, antagonist, learning and memory, Alzheimer's disease, neurodegeneration, passive avoidance paradigm, novel object recognition, behavioral research

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Authors: Anindita Sen

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Oral fluid is a promising diagnostic matrix for drugs of abuse compared to urine and serum. Detection of methamphetamine in oral fluid would pave way for the easy evaluation of impairment in drivers during roadside drug testing as well as ensure safe working environments by facilitating evaluation of impairment in employees at workplaces. A membrane-based point-of-care (POC) friendly pre-treatment technique has been developed which aided elimination of interferences caused by salivary proteins and facilitated the demonstration of methamphetamine detection in saliva using a gold nanoparticle based colorimetric aptasensor platform. It was found that the colorimetric response in saliva was always suppressed owing to the matrix effects. By navigating the challenging interfering issues in saliva, we were successfully able to detect methamphetamine at nanomolar levels in saliva offering immense promise for the translation of these platforms for on-site diagnostic systems. This subsequently motivated the development of a handheld portable light meter device that can reliably transduce the aptasensors colorimetric response into absorbance, facilitating quantitative detection of analyte concentrations on-site. This is crucial due to the prevalent unreliability and sensitivity problems of the conventional drug testing kits. The fabricated light meter device response was validated against a standard UV-Vis spectrometer to confirm reliability. The portable and cost-effective handheld detector device features sensitivity comparable to the well-established UV-Vis benchtop instrument and the easy-to-use device could potentially serve as a prototype for a commercial device in the future.

Keywords: aptasensors, colorimetric gold nanoparticle assay, point-of-care, oral fluid

Procedia PDF Downloads 39

Authors: Nunila Ferreira de Oliveira, Silvana Martins Mishima

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Diabetes mellitus type 2 (DM2) prevalence, is increasing on the world, in Brazil is considered a public health problem. Treatment focuses on glycemic control depending primarily of lifestyle changes - not drug treatment (NDT), may involve drug therapy (DT) and requires continuous health monitoring. In Brazil this monitoring is performed by the Unified Health System (SUS) through Primary Health Care (PHC), which stimulate people with DM2 empowerment for care management. SUS was approved in 1988 and the PHC operationalization was strengthened with the creation of the Family Health Strategy (FHS) in 1994. Our aim was to analyze the people with DM2 participation in front of the care management health monitoring in the FHS. Qualitative research was carried out through non-participant observation of attendance of 25 people with DM2 in the FHS and interviewed at home. Ethical guidelines were followed. It was found that people with DM2 only follow professionals’ recommendations that make sense according to their own conceptions of health/disease; most of them emphasize the importance of (DT) with little emphasis on the NDT, was found great difficulty in the NDT and lack of knowledge about the disease and care. As regards monitoring the FHS, were observed therapeutic practices based on the bio medical model, although the APS search for another care perspective; NDT is not systematically accompanied by the health team and takes place a few educational activities on the DM2 in the FHS, with low user adoption. The work of the FHS is done by multidisciplinary teams, but we see the need for greater participation of nurses in clinical-care follow-up of this population and may also act in adapting to the NDT. Finally we emphasize the need for professional practices that consider the difficulties to care management by people with DM2, especially because of the NDT. It is noticed that the measures recommended by the FHS professionals are not always developed by people with DM2. We must seek the empowerment of people with DM2 to manage the form of care associated with the FHS team, seeking to reduce the incidence of complications and higher quality of life.

Keywords: diabetes mellitus, primary health care, nursing, management of care

Procedia PDF Downloads 451

Authors: Mukul Sharma, Madhusmita Das, Sundeep Chaitanya Vedithi

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Leprosy is a chronic human disease caused by Mycobacterium leprae, that cannot be cultured in vitro. Though treatable with multidrug therapy (MDT), recently, bacteria reported resistance to multiple antibiotics. Targeting DNA replication and repair pathways can serve as the foundation of developing new anti-leprosy drugs. Due to the absence of an axenic culture medium for the propagation of M. leprae, studying cellular processes, especially those belonging to DNA repair pathways, is challenging. Genomic understanding of M. Leprae harbors several protein-coding genes with no previously assigned function known as 'hypothetical proteins'. Here, we report identification and expression of known and hypothetical DNA repair genes from a human skin biopsy and mouse footpads that are involved in base excision repair, direct reversal repair, and SOS response. Initially, a bioinformatics approach was employed based on sequence similarity, identification of known protein domains to screen the hypothetical proteins in the genome of M. leprae, that are potentially related to DNA repair mechanisms. Before testing on clinical samples, pure stocks of bacterial reference DNA of M. leprae (NHDP63 strain) was used to construct standard graphs to validate and identify lower detection limit in the qPCR experiments. Primers were designed to amplify the respective transcripts, and PCR products of the predicted size were obtained. Later, excisional skin biopsies of newly diagnosed untreated, treated, and drug resistance leprosy cases from SIHR & LC hospital, Vellore, India were taken for the extraction of RNA. To determine the presence of the predicted transcripts, cDNA was generated from M. leprae mRNA isolated from clinically confirmed leprosy skin biopsy specimen across all the study groups. Melting curve analysis was performed to determine the integrity of the amplification and to rule out primer‑dimer formation. The Ct values obtained from qPCR were fitted to standard curve to determine transcript copy number. Same procedure was applied for M. leprae extracted after processing a footpad of nude mice of drug sensitive and drug resistant strains. 16S rRNA was used as positive control. Of all the 16 genes involved in BER, DR, and SOS, differential expression pattern of the genes was observed in terms of Ct values when compared to human samples; this was because of the different host and its immune response. However, no drastic variation in gene expression levels was observed in human samples except the nth gene. The higher expression of nth gene could be because of the mutations that may be associated with sequence diversity and drug resistance which suggests an important role in the repair mechanism and remains to be explored. In both human and mouse samples, SOS system – lexA and RecA, and BER genes AlkB and Ogt were expressing efficiently to deal with possible DNA damage. Together, the results of the present study suggest that DNA repair genes are constitutively expressed and may provide a reference for molecular diagnosis, therapeutic target selection, determination of treatment and prognostic judgment in M. leprae pathogenesis.

Keywords: DNA repair, human biopsy, hypothetical proteins, mouse footpads, Mycobacterium leprae, qPCR

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Authors: Rania Hanafi Said, Rasha Mohamed Taha

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

Keywords: Immunohistochemistry, Nanochitosan, porphyromonas gingivitis, Tetracycline

Procedia PDF Downloads 77

Authors: Umme Hani, H. G. Shivakumar, M. D. Younus Pasha

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The purpose of this work was to design and optimize a novel vaginal drug delivery system for more effective treatment against vaginal candidiasis. To achieve a better therapeutic efficacy and patient compliance in the treatment for vaginal candidiasis, herbal antifungal agent Curcumin which is 2.5 fold more potent than fluconazole at inhibiting the adhesion of candida albicans has been formulated in a bio-adhesive vaginal film. Curcumin was formulated in bio-adhesive film formulations that could be retained in the vagina for prolonged intervals. The polymeric films were prepared by solvent evaporation and optimized for various physicodynamic and aesthetic properties. Curcumin HPβCD (Hydroxypropyl β Cyclodextrin) was first developed to increase the solubility of curcumin. The formation of the Curcumin HPβCD complex was characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and FT-IR and evaluated for its solubility. Curcumin HPβCD complex was formulated in a bio-adhesive film using hydroxypropyl methyl cellulose (HPMC) and Carbopol 934P and characterized. DSC and FT-IR data of Curcumin HPβCD indicate there was complex formation between the drug and HPβCD. The little moisture content (8.02±0.34% w/w) was present in the film, which helps them to remain stable and kept them from being completely dry and brittle. The mechanical properties, tensile strength, and percentage elongation at break reveal that the formulations were found to be soft and tough. The films showed good peelability, relatively good swelling index, and moderate tensile strength and retained vaginal mucosa up to 8 h. The developed Curcumin vaginal film could be a promising safe herbal medication and can ensure longer residence at the vagina and provide an efficient therapy for vaginal candidiasis.

Keywords: curcumin, curcumin-HPβCD complex, bio-adhesive vaginal film, vaginal candidiasis, 23 factorial design

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Authors: Jungkyun Im

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain and reducing inflammation. They are nonselective inhibitors of two isoforms of COX, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and thereby inhibiting the production of hormone-like lipid compounds such as, prostaglandins and thromboxanes which cause inflammation, pain, fever, platelet aggregation, etc. In addition, recently there are many research articles reporting the neuroprotective effect of NSAIDs in neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the clinical use of NSAIDs in these diseases is limited by low brain distribution. Therefore, in order to assist the in-depth investigation on the pharmaceutical mechanism of flurbiprofen in neuroprotection and to make flurbiprofen a more potent drug to prevent or alleviate neurodegenerative diseases, delivery of flurbiprofen to brain should be effective and sufficient amount of flurbiprofen must penetrate the BBB thus gaining access into the patient’s brain. We have recently developed several types of guanidine-rich molecular carriers with high molecular weights and good water solubility that readily cross the blood-brain barrier (BBB) and display efficient distributions in the mouse brain. The G8 (having eight guanidine groups) molecular carrier based on D-sorbitol was found to be very effective in delivering anticancer drugs to a mouse brain. In the present study, employing the same molecular carrier, we prepared the flurbiprofen conjugate and studied its BBB permeation by mouse tissue distribution study. Flurbiprofen was attached to a molecular carrier with a fluorescein probe and multiple terminal guanidiniums. The conjugate was found to internalize into live cells and readily cross the BBB to enter the mouse brain. Our novel synthetic flurbiprofen conjugate will hopefully delivery NSAIDs into brain, and is therefore applicable to the neurodegenerative diseases treatment or prevention.

Keywords: flurbiprofen, drug delivery, molecular carrier, organic synthesis

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Authors: Angalabiri-Owei E. Bekekeme, Brambaifa Nelson

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In view of the peculiar environment of the Niger Delta, access to modern health care is limited, hence the inhabitants especially those in the swampy areas resorts to sourcing for alternatives cure for their ailments using plants commonly found in this area without scientific evaluation. Rhizophora racemosa, G. F. Meyer (Rhizophoraceae) is the most abundant mangrove plant in the Niger Delta Area of Nigeria. The plant has been observed to be used for relief of a toothache and dysmenorrhoea among some Ijaw communities in the region. This work has revealed the likely potential of the plant in drug discovery and development. The crude methanol extract at doses of 300 mg/kg and 600 mg/kg (intraperitoneal) were tested for analgesic effect using fresh egg albumin induced inflammatory pain and Randall–Sellito method to assess the pain threshold. The anti-inflammatory effect was also evaluated with the extract at doses of 300 mg/kg and 600 mg/kg (intraperitoneal) using acute inflammatory model; fresh egg albumin induced paw oedema and assessed using Plethysmometer in rats. The methanol extracts 300 mg/kg and 600 mg/kg exhibited a significant (P < 0.001) and dose-dependent analgesic activity compared with the negative control and a standard drug diclofenac using ANOVA with Least Significant Difference post hoc test as evidenced by increased pain threshold. Also, the extract significantly (P < 0.001) reduced the rat paw oedema induced by the sub plantar injection of fresh egg albumin when compared with the negative control and a standard diclofenac using above statistical methods. This study revealed that the plant possesses analgesic and anti-inflammatory activities hence provide scientific bases for use as medicine.

Keywords: analgesic, anti-inflammatory, plethysmometer, Rhizophora racemosa

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Authors: Jose D. Zapata-Torres, Esteban Naranjo-Gutiérrez, Angela M. Martínez-Valencia, Jenny J. Chaparro-Gutiérrez, David Villar-Argaiz

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Reports of drug resistance have been made in every livestock host and to every anthelmintic class. In some regions of world, the extremely high prevalence of multi-drug resistance in nematodes of sheep and goats threatens the viability of small-ruminant industries. In the region of Antioquia, Colombia, no reports of nematode resistance have been documented due to a lack of veterinary diagnostic laboratories. The objective of this study was to evaluate the efficacy of albendazole, fenbendazole, and levamisole to control gastrointestinal nematodes in goat farms of Antioquia by doing fecal egg count reduction tests. A total of 139 crossbreed goats from four separate farms were sampled for feces prior to, and 14 days following anthelmintc treatments. Individual fecal egg counts were performed using the modified three chamber McMaster technique. The anthelmintics administered at day 0 were albendazole (farm 1, n=63), fenbendazole (farm 2, n=20), and levamisole (farm 3 and 4, n= 37, and 19). Larval cultures were used to identify the genus of nematodes using Baermann`s technique and the morphological keys for identification of L3 in small ruminants. There was no difference in fecal egg counts between 0 and 14, with means (±SD) of 1681,5 ± 2121,5 and 1715,12 ± 1895,4 epg (eggs per gram), respectively. The egg count reductions for each anthelmintic and farm were 25,86% for albendazole (farm 1), 0% for fenbendazole (farm 2), 0% (farm 3), and 5,5% (farm 4) for levamisole. The genus of nematodes identified was predominantly Haemonchus spp., with 70,27% and 82,81% for samples from day 0 and 14, respectively. These results provide evidence of a total state of resistance to 3 common anthelmintics. Further research is needed to design integrate management programs to control nematodes in small ruminants in Colombia.

Keywords: anthelmintics, goat, haemonchus, resistance

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Authors: Dong Tran, Thanh Dac Van, Ly Le

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Hemagglutinin (HA) and Neuraminidase (NA) play an important role in host immune evasion across influenza virus evolution process. The correlation between HA and NA evolution in respect to epitopic evolution and drug interaction has yet to be investigated. In this study, combining of sequence to structure evolution and statistical analysis on epitopic/binding site specificity, we identified potential therapeutic features of HA and NA that show specific antibody binding site of HA and specific binding distribution within NA active site of current inhibitors. Our approach introduces the use of sequence variation and molecular interaction to provide an effective strategy in establishing experimental based distributed representations of protein-protein/ligand complexes. The most important advantage of our method is that it does not require complete dataset of complexes but rather directly inferring feature interaction from sequence variation and molecular interaction. Using correlated sequence analysis, we additionally identified co-evolved mutations associated with maintaining HA/NA structural and functional variability toward immunity and therapeutic treatment. Our investigation on the HA binding specificity revealed unique conserved stalk domain interacts with unique loop domain of universal antibodies (CR9114, CT149, CR8043, CR8020, F16v3, CR6261, F10). On the other hand, NA inhibitors (Oseltamivir, Zaninamivir, Laninamivir) showed specific conserved residue contribution and similar to that of NA substrate (sialic acid) which can be exploited for drug design. Our study provides an important insight into rational design and identification of novel therapeutics targeting universally recognized feature of influenza HA/NA.

Keywords: influenza virus, hemagglutinin (HA), neuraminidase (NA), sequence evolution

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Authors: Priya Patel, Paresh Patel, Mihir Raval

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Silibinin, a flavanone as an antimicrotubular agent used in the treatment of cancer, was encapsulated in nanoparticles (NPs) of poly (lactide-co-glycolide) (PLGA) polymer using the spray-drying technique. The effects of various experimental parameters were optimized by box-behnken experimental design. Production yield, encapsulation efficiency and dissolution study along with characterization by scanning electron microscopy, DSC, FTIR followed by bioavailability study. Particle size and zeta potential were evaluated by using zetatrac particle size analyzer. Experimental design it was evaluated that inlet temperature and polymer concentration influence on the drug release. Feed flow rate impact on particle size. Results showed that spray drying technique yield 149 nm indicate nanosize range. The small size of the nanoparticle resulted in an enhanced cellular entry and greater bioavailability. Entrapment efficiency was found between 89.35% and 98.36%. Zeta potential shows good stability index of nanoparticle formulation. The in vitro release studies indicated the silibinin loaded PLGA nanoparticles provide controlled drug release over a period of 32 h. Pharmacokinetic studies demonstrated that after oral administration of silibinin-loaded PLGA nanoparticles to rats at a dose of 10 mg/kg, relative bioavailability was enhanced about 8.85-fold, compared to silibinin suspension as control hence, this investigation demonstrated the potential of the experimental design in understanding the effect of the formulation variables on the quality of silibinin loaded PLGA nanoparticles. These results describe an effective strategy of silibinin loaded PLGA nanoparticles and might provide a promising approach against the cancer.

Keywords: silibinin, cancer, nanoparticles, PLGA, bioavailability

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Authors: Salwa M. Almomen, Mona A. Almaghrabi, Saja M. Alhabardi, Adel A. Alrwisan

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Background: Hepatotoxicity is a major reason for medication withdrawal from the markets. Unfortunately, serious adverse hepatic effects can occur after marketing with limited indicators during clinical development. Therefore, finding possible predictors for hepatotoxicity might guide the monitoring program of various stakeholders. Methods: We examined the clinical review documents for drugs approved in the US from 2011 to 2016 to evaluate their hepatic safety profile. Predictors: we assessed whether these medications meet Hy’s Law with hepatotoxicity grade ≥ 3, labeled hepatic adverse effects at approval, or accelerated approval status. Outcome: post-marketing regulatory action related to hepatotoxicity, including product withdrawal or updates to warning, precaution, or adverse effects sections. Statistical analysis: drugs were included in the analysis from the time of approval until the end of 2019 or the first post-marketing regulatory action related to hepatotoxicity, whichever occurred first. The hazard ratio (HR) was estimated using Cox-regression analysis. Results: We included 192 medications in the study. We classified 48 drugs as having grade ≥ 3 hepatotoxicities, 43 had accelerated approval status, and 74 had labeled information about hepatotoxicity prior to marketing. The adjusted HRs for post-marketing regulatory action for products with grade ≥ 3 hepatotoxicity was 0.61 (95% confidence interval [CI], 0.17-2.23), 0.92 (95%CI, 0.29-2.93) for a drug approved via accelerated approval program, and was 0.91 (95%CI, 0.33-2.56) for drugs with labeled hepatotoxicity information at approval time. Conclusion: This study does not provide conclusive evidence on the association between post-marketing regulatory action and grade ≥ 3 hepatotoxicity, accelerated approval status, or availability of labeled information at approval due to sampling size and channeling bias.

Keywords: accelerated approvals, hepatic adverse effects, drug-induced liver injury, hepatotoxicity predictors, post-marketing withdrawal

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Authors: Levent Basayigit, Sinan Demir, Burhan Kara, Yusuf Ucar

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Cannabis is mostly used for drug production. In some countries, an excessive amount of illegal cannabis is cultivated and sold. Most of the illegal cannabis cultivation occurs on the lands far from settlements. In farmlands, it is cultivated with other crops. In this method, cannabis is surrounded by tall plants like corn and sunflower. It is also cultivated with tall crops as the mixed culture. The common method of the determination of the illegal cultivation areas is to investigate the information obtained from people. This method is not sufficient for the determination of illegal cultivation in remote areas. For this reason, more effective methods are needed for the determination of illegal cultivation. Remote Sensing is one of the most important technologies to monitor the plant growth on the land. The aim of this study is to monitor cannabis cultivation area using satellite imagery. The main purpose of this study was to develop an applicable method for monitoring the cannabis cultivation. For this purpose, cannabis was grown as single or surrounded by the corn and sunflower in plots. The morphological characteristics of cannabis were recorded two times per month during the vegetation period. The spectral signature library was created with the spectroradiometer. The parcels were monitored with high-resolution satellite imagery. With the processing of satellite imagery, the cultivation areas of cannabis were classified. To separate the Cannabis plots from the other plants, the multiresolution segmentation algorithm was found to be the most successful for classification. WorldView Improved Vegetative Index (WV-VI) classification was the most accurate method for monitoring the plant density. As a result, an object-based classification method and vegetation indices were sufficient for monitoring the cannabis cultivation in multi-temporal Earthwiev images.

Keywords: Cannabis, drug, remote sensing, object-based classification

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Authors: Nasibeh Azizi Khereshki

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Olive leaf (OL) extract as a green reductant agent was utilized for the biogenic synthesis of silver nanoparticles (Ag NPs) for the first time in this study, and then its performance was evaluated for colorimetric detection of Fe3+ in different media. Some analytical methods were used to characterize the nanosensor. The effective sensing parameters were optimized by central composite design (CCD) combined with response surface methodology (RSM) application. Then, the prepared material's applicability in antibacterial and optical chemical sensing for naked-eye detection of Fe3+ ions in aqueous solutions were evaluated. Furthermore, OL-Ag NPs-loaded paper strips were successfully applied to the colorimetric visualization of Fe3+. The colorimetric probe based on OL-AgNPs illustrated excellent selectivity and sensitivity towards Fe3+ ions, with LOD and LOQ of 0.81 μM and 2.7 μM, respectively. In addition, the developed method was applied to detect Fe3+ ions in real water samples and validated with a 95% confidence level against a reference spectroscopic method.

Keywords: Ag NPs, colorimetric detection, Fe(III) ions, green synthesis, olive leaves

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Authors: A. Banerjee, C. Grazon, B. Nadal, T. Pons, Y. Krishnan, B. Dubertret

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Quantum Dots (QDs) have emerged as novel fluorescent probes for biomedical applications. The photophysical properties of QDs such as broad absorption, narrow emission spectrum, reduced blinking, and enhanced photostability make them advantageous over organic fluorophores. However, for some biological applications, QDs need to be first targeted to specific intracellular locations. It parallel, base pairing properties and biocompatibility of DNA has been extensively used for biosensing, targetting and intracellular delivery of numerous bioactive agents. The combination of the photophysical properties of QDs and targettability of DNA has yielded fluorescent, stable and targetable nanosensors. QD-DNA conjugates have used in drug delivery, siRNA, intracellular pH sensing and several other applications; and continue to be an active area of research. In this project, a novel method to synthesise QD-DNA conjugates and their applications in bioimaging are investigated. QDs are first solubilized in water using a thiol based amphiphilic co-polymer and, then conjugated to amine functionalized DNA using a heterobifunctional linker. The conjugates are purified by size exclusion chromatography and characterized by UV-Vis absorption and fluorescence spectroscopy, electrophoresis and microscopy. Parameters that influence the conjugation yield such as reducing agents, the excess of salt and pH have been investigated in detail. In optimized reaction conditions, up to 12 single-stranded DNA (15 mer length) can be conjugated per QD. After conjugation, the QDs retain their colloidal stability and high quantum yield; and the DNA is available for hybridization. The reaction has also been successfully tested on QDs emitting different colors and on Gold nanoparticles and therefore highly generalizable. After extensive characterization and robust synthesis of QD-DNA conjugates in vitro, the physical properties of these conjugates in cellular milieu are being invistigated. Modification of QD surface with DNA appears to remarkably alter the fate of QD inside cells and can have potential implications in therapeutic applications.

Keywords: bioimaging, cellular targeting, drug delivery, photostability

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Authors: Shamila Manie, Soraya Maart, Ayesha Osman

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Introduction: People diagnosed with multidrug resistant pulmonary tuberculosis (MDR-PTB) is subjected to prolonged hospitalization in South Africa. It has thus become essential for research to shift its focus from a purely medical approach, but to include social and environmental factors when looking at the impact of the disease on those affected. Aim: To explore the factors affecting individuals with multi-drug resistant pulmonary tuberculosis during long-term hospitalization using the comprehensive ICF core-sets for obstructive pulmonary disease (OPD) and cardiopulmonary (CPR) conditions at Brooklyn Chest Hospital (BCH). Methods: A quantitative descriptive, cross-sectional study design was utilized. A convenient sample of 19 adults at Brooklyn Chest Hospital were interviewed. Results: Most participants reported a decrease in exercise tolerance levels (b455: n=11). However it did not limit participation. Participants reported that a lack of privacy in the environment (e155) was a barrier to health. The presence of health professionals (e355) and the provision of skills development services (e585) are facilitators to health and well-being. No differences exist in the functional ability of HIV positive and negative participants in this sample. Conclusion: The ICF Core Sets appeared valid in identifying the barriers and facilitators experienced by individuals with MDR-PTB admitted to BCH. The hospital environment must be improved to add to the QoL of those admitted, especially improving privacy within the wards. Although the social grant is seen as a facilitator, greater emphasis must be placed on preparing individuals to be economically active in the labour for when they are discharged.

Keywords: multidrug resistant tuberculosis, MDR ICF core sets, health-related quality of life (HRQoL), hospitalization

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Authors: Jaeyoung Lee, Minji Je

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Objectives: The adolescents not attending school are named out-of-school adolescents. They are more vulnerable to health management and are likely to be exposed to a number of risk factors. This study was conducted to investigate the problem behavior of out-of-school adolescents and analyze the difference caused by gender. Methods: In this study, the problem behaviors of out-of-school adolescents, the vulnerable class, were defined in 8 types and based on this definition, the survey on run away from home, drop out, prostitution, violence, internet game addiction, theft, drug addiction, and smoking was conducted. The study was conducted in a total of 507 out-of-school adolescents, including 342 males, and 165 females. The type, frequency and start time of the 8 problem behaviors were identified. The collected data were analyzed with chi-square test and t-test using SPSS statistics 22. Results: Among the problem behaviors of the subjects, violence ( =17.41, p < .001), internet game addiction ( =16.14, p < .001), theft ( =22.48, p < .001), drug addiction ( =4.17, p=.041), and smoking ( =3.90, p=.048) were more significantly high in male out-of-school adolescents than female out-of-school adolescents. In addition, the frequency of the problem behavior was higher in male out-of-school adolescents with statistical significance than in female out-of-school adolescents (t=5.08, p= < .001). In terms of the start time of the problem behavior, only internet game addiction was higher in male out-of-school adolescents with the statistical significance than in female out-of-school adolescents ( =6.22, p=.032). No statistically significant difference was found in other problem behaviors (p > .05). Conclusions: In this study, it was found that gender difference in problem behaviors of out-of-school adolescents exists, and its frequency and difference of types were identified. When the social countermeasures were provided for those adolescents, a distinguished approach is required depending on the patterns of problem behavior and gender. When preparing policy alternatives and interventions for out-of-school adolescents, it is required to reflect the results of this study.

Keywords: addictive behavior, adolescent, gender, problem behavior

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Authors: Akbar Esmaeili, Azadeh Asgari

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Essential oils’ unique and practical properties have been widely reported in recent years. Still, the sensitivity of critical oils to environmental factors and their poor solubility in aqueous solutions have limited their use in industries. Therefore, we encapsulated C. copticum essential oil in chitosan nanoparticles by emulsion-ionic gelation with sodium tripolyphosphate and sodium hexametaphosphate cross-linkers. The nanoparticles showed a round shape with an average size of 30-80 nm and a regular distribution. The release profile in the laboratory environment showed a burst in the initial release and then a stable release of C. copticum essential oil from chitosan nanoparticles at different pH. Antioxidant and antibacterial properties of C. copticum essential oil before and after the encapsulation process were evaluated by 2,2-diphenyl-1-picrylhydrazyl radical and disc diffusion methods, respectively. The results showed that the encapsulation of C. copticum essential oil in chitosan nanoparticles could protect its quality and bioactive compounds and improve the properties of the crucial oil.

Keywords: essential oils, Carum copticum, biological activities, nanotechnology

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Authors: Danylo Brindak, Viktor Liashko, Olexander Chepurniy

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Despite considerable experience in implementation of the best international approaches and services within response to epidemy of multi-drug resistant tuberculosis, the results of situation analysis indicate the presence of faults in this area. In 2014, Ukraine (for the first time) was included in the world’s five countries with the highest level of drug-resistant tuberculosis. The effectiveness of its treatment constitutes only 35% in the country. In this context, the increase in allocation of funds to control the epidemic of multidrug-resistant tuberculosis does not produce perceptible positive results. During 2001-2016, only the Global Fund to fight AIDS, Tuberculosis, and Malaria allocated to Ukraine more than USD 521,3 million for programs of tuberculosis and HIV/AIDS control. However, current conditions in post-Semashko system create little motivation for rational use of resources or cost control at inpatient TB facilities. There is no motivation to reduce overdue hospitalization and to target resources to priority sectors of modern tuberculosis control, including a model of care focused on the patient. In the presence of a line-item budget at medical institutions, based on the input factors as the ratios of beds and staff, there is a passive disposal of budgetary funds by health care institutions and their employees who have no motivation to improve quality and efficiency of service provision. Outpatient treatment of tuberculosis is being implemented in Ukraine since 2011 and has many risks, namely creation of parallel systems, low consistency through dependence on funding for the project, reduced the role of the family doctor, the fragmentation of financing, etc. In terms of reforming approaches to health system financing, which began in Ukraine in late 2016, NGO Infection Control in Ukraine conducted piloting of a new, motivating method of remuneration of employees in primary health care. The innovative aspect of this funding mechanism is cost according to results of treatment. The existing method of payment on the basis of the standard per inhabitant (per capita ratio) was added with motivating costs according to results of work. The effectiveness of such treatment of TB patients at the outpatient stage is 90%, while in whole on the basis of a current system the effectiveness of treatment of newly diagnosed pulmonary TB with positive swab is around 60% in the country. Even though Ukraine has 5.24 TB beds per 10 000 citizens. Implemented pilot model of ambulatory treatment will be used for the creation of costs system according to results of activities, the integration of TB and primary health and social services and their focus on achieving results, the reduction of inpatient treatment of tuberculosis.

Keywords: health care reform, multi-drug resistant tuberculosis, outpatient treatment efficiency, tuberculosis

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