Search results for: drug of abuse
Commenced in January 2007
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Edition: International
Paper Count: 2442

Search results for: drug of abuse

1482 Application of Computational Chemistry for Searching Anticancer Derivatives of 2-Phenazinamines as Bcr-Abl Tyrosine Kinase Inhibitors

Authors: Gajanan M. Sonwane

Abstract:

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

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1481 Pulsed-Wave Doppler Ultrasonographic Assessment of the Maximum Blood Velocity in Common Carotid Artery in Horses after Administration of Ketamine and Acepromazine

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

Abstract:

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

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1480 Mathematical Modelling of Blood Flow with Magnetic Nanoparticles as Carrier for Targeted Drug Delivery in a Stenosed Artery

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

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1479 Socio-Economic and Psychological Factors of Moscow Population Deviant Behavior: Sociological and Statistical Research

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

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1478 Examining Child Rape Provisions of Bangladesh in Comparison with Other South Asian Countries

Authors: Monira Nazmi Jahan

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Child rape or child abuse is a serious and fearsome crime against children, which is an epidemic almost in every state of today’s world. However, in the case of Bangladesh, the scenario is terrifying. The objective of this paper is to examine the laws relating to child rape in Bangladesh as according to a renowned Daily Newspaper 'Prothom Alo', nearly 346 children are being raped since January 2019. This paper discusses and draws the difference of child rape provisions of Bangladesh with other South-Asian countries, comprises of India, Maldives, Pakistan, Sri Lanka, Nepal, Bhutan, and Afghanistan. In Bangladesh, girls below 18 years are considered to be a child. ‘The Penal Code, 1860’ and a special law ‘Nari O Shishu Nirjatan Daman Ain, 2012’ provides that any person committing child rape will be punished with rigorous life imprisonment and fine. This piece of law also gives provisions for punishment in case of child’s death after the commission of rape and gang rape, and the punishment is the death penalty. In India there is ‘The Protection of Children from Sexual Offences Act, 2012’ (POSCO) which has separate provisions for sexual assault, penetrative sexual assault and aggravated penetrative sexual assault by different categories of person such as relatives, institutional officers and trustees and also for mentally and physically challenged child victims and provides punishment up to death penalty. In Pakistan, there is ‘Pakistan Penal Code Amended Act, 2016’ which has only two provisions for child rape. In case offence committed by one person, the punishment is 10 to 25 years of imprisonment and fine. In case of offence committed by two or more persons, each shall be liable to death or imprisonment for life. Unfortunately, Afghanistan has no laws for the protection of rape victims of women let alone children, whereas there are a lot of child rape cases, including both girls and boys who are used for sexual slavery. The Maldives has a special law named ‘Special Provisions Act to Deal with Child Sex Abuse Offenders.’ This has categorized the offenders like POSCO and has provided punishments accordingly. The punishments are: punishments range from 1 to 25 years accordingly, whereas Bangladesh has lesser provisions, but the gravity and duration of punishments are much higher. The Penal Code of Sri Lanka imposes a minimum sentence of 10 years for those convicted of raping a child under 18 years. In Bhutan, child rape provision is made according to the age of a child. ‘The Penal Code of Bhutan, 2004’, mentions provisions for the rape of a child in case of child rape below and above 12 years, gang rape of a child below and above 12 years and has graded the punishments as first, second and third degree. Though Bangladesh has better provisions for punishments, the ages are not categorized in the laws. In Nepal there is ‘Act relating to Children, 2018’ provisions are made for offenders who use or cause or engage child sexual exploitation, and the punishment is same for rape offenders according to prevailing laws in Nepal. No separate punishments for child offenders are made. The ultimate conclusion that can be drawn is Bangladesh has better punishments than all other South-Asian countries and same punishment as India however, Bangladesh can make or amend the laws and categorize offenders as like POSCO of India, Special provisions of Maldives and Bhutan.

Keywords: child rape, death penalty, sexual slavery, South Asia

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1477 The Effects of Resident Fathers on the Children in South Africa: The Case of Selected Household in Golf View, Alice Town, Eastern Cape Province

Authors: Gabriel Acha Ekobi

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Fathers play a crucial role in meeting family needs such as affection, protection, and socio-economic needs of children in the world in general and South Africa in particular. Fathers’ role in children’s lives is important in providing socialization, leadership skills, and teaching societal norms. Fathers influence is very significant for children’s well-being and development as it provides the child with moral lessons, guidance, and economic support. However, there is a paucity of information regarding the effects of fathers on children. In addition, despite legal frameworks such as the African Charter on the Rights and Welfare of the child (1999) introduced by the African Union to promote child rights nevertheless, it appears maltreatment, abuse, and poor health care continue to face children. Also, the Constitution of 1996 of the Republic of South Africa (Section 28 of the Bill of Rights) and the Children’s Act 38 of 2005 were introduced by the South African government to foster the rights of children. Nevertheless, these legal frameworks remain ineffective as children’s rights are still neglected by resident fathers. This paper explores the impact of resident fathers on children in the Golf View, Alice town of the Eastern Cape Province, South Africa. A qualitative research method and an exploratory research design were utilized, and 30 participants took part in the study. The participants comprised of single mothers or caregivers of children, resident fathers and social workers. Eighteen (18) single mothers or caregivers, 10 resident fathers, and two (2) social workers participated in the study. Data was collected using semi-structured and unstructured interviews and analysed thematically. Two main themes were identified: the role of fathers on children and the effects of resident fathers on children. The study found that the presence of fathers in the lives of children prevented psychosocial issues such as stress, depression, violence, and substance abuse. A father’s presence in a household was crucial in instilling moral values in children. This allowed them to build positive characters such as respect, kindness, humility, and compassion. Children with more involved fathers tend to have fewer impulse control problems, longer attention spans, and a higher level of sociability. The study concludes that the fathers’ role prevented anxiety, depression, and stress and led to the improvement of children’s education performance. Nevertheless, the absence of a father as a role model to act as a leader by instilling moral values hinders positive behaviours in children. This study recommended that occupational training and life skills programmes should be introduced by the government and other stakeholders to empower the fathers as this might provide the platform for them to bring up their children properly.

Keywords: children, fathering, household, resident, single parent

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1476 Explaining the Role of Iran Health System in Polypharmacy among the Elderly

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

Abstract:

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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1475 Biological Studies of N-O Donor 4-Acypyrazolone Heterocycle and Its Pd/Pt Complexes of Therapeutic Importance

Authors: Omoruyi Gold Idemudia, Alexander P. Sadimenko

Abstract:

The synthesis of N-heterocycles with novel properties, having broad spectrum biological activities that may become alternative medicinal drugs, have been attracting a lot of research attention due to the emergence of medicinal drug’s limitations such as disease resistance and their toxicity effects among others. Acylpyrazolones have been employed as pharmaceuticals as well as analytical reagent and their application as coordination complexes with transition metal ions have been well established. By way of a condensation reaction with amines acylpyrazolone ketones form a more chelating and superior group of compounds known as azomethines. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one was reacted with phenylhydrazine to get a new phenylhydrazone which was further reacted with aqueous solutions of palladium and platinum salts, in an effort towards the discovery of transition metal based synthetic drugs. The compounds were characterized by means of analytical, spectroscopic, thermogravimetric analysis TGA, as well as x-ray crystallography. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one phenylhydrazone crystallizes in a triclinic crystal system with a P-1 (No. 2) space group based on x-ray crystallography. The bidentate ON ligand formed a square planar geometry on coordinating with metal ions based on FTIR, electronic and NMR spectra as well as magnetic moments. Reported compounds showed antibacterial activities against the nominated bacterial isolates using the disc diffusion technique at 20 mg/ml in triplicates. The metal complexes exhibited a better antibacterial activity with platinum complex having an MIC value of 0.63 mg/ml. Similarly, ligand and complexes also showed antioxidant scavenging properties against 2, 2-diphenyl-1-picrylhydrazyl DPPH radical at 0.5mg/ml relative to ascorbic acid (standard drug).

Keywords: acylpyrazolone, antibacterial studies, metal complexes, phenylhydrazone, spectroscopy

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1474 Dowry System and Gender Discrimination

Authors: Vanitha Dapparabail

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Dowry is a system attached to Indian marriage system, it is practice of exchanging the goods and articles in a majority of Indian weddings. Although its practice became illegal in 1961, dowry flourishes among all social classes. Families of the bride and groom negotiate transfer of assets to the groom and his family in exchange for marrying the bride, often within the context of an arranged marriage. Dissatisfaction with the amount of dowry may result in abuse of the bride. In extreme cases “dowry deaths” or the murder of the bride by her husband and his family take place. This article conducts a feminist psychological analysis of the dowry phenomenon, its link to domestic violence against women, and the role of the perpetrators. Existing and new explanations of the dowry system and its ramifications are explored. Psychologically dowry system is greater mental stress for the Indian women and it is a really a part of gender discrimination. This part of the study can explore the amount of gender discrimination in Indian society.

Keywords: Dowry system, violence, gender discrimination, India

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1473 Reliability of Clinical Coding in Accurately Estimating the Actual Prevalence of Adverse Drug Event Admissions

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

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1472 Relationship Between Family Factors and Tendency to Addiction

Authors: Farzaneh Golshekoh

Abstract:

The aim of this study was to examine the relationship between religious beliefs, family responsibility and emotional atmosphere with a tendency to addiction in high school female students in Ahwaz. The sample consisted of 250 students who were selected by cluster random sampling from among all high school female students in Ahvaz. Measuring tools were Iranian tendency towards addiction (IAPS), responsibility California Psychological Inventory (CPI), emotional family atmosphere (AFC) and religious beliefs. The simple correlation coefficient at α=0/05 showed that there is a significant negative relationship between religious beliefs, family responsibility and emotional atmosphere with a tendency to abuse female students. The regression analysis showed that the variables of the emotional atmosphere of the family and religious beliefs as predictors of female students have a tendency to addiction.

Keywords: emotional atmosphere, family responsibility, religious beliefs, tendency to addiction

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1471 Mandatory Wellness Assessments for Medical Students at the University of Ottawa

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

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1470 Russian Law Enforcement Moonlighting Enterprise and Corruption after 2009 Police reform

Authors: Serguei Cheloukhine

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This study examines corrupting and moonlighting enterprise among Russian law enforcement (Police) since the 2009 Police Reform (hereto forward referred to as Reform). This research is based on the survey of about two dozen police officers in Russia’s regions. In addition, we analyzed statistics on crime, policing and socio-economic situation in Russian regions. Congruently, some data on the police officer’s off-duty activities was collected from the Internet sites. These Reforms sought to curb corruption at all levels of the Russian civil service and among uniformed law enforcement (Police) personnel. Many thought that the rebranding of the Militsiya as ‘Politsiya’ (Police) would have a transformational effect, both within the organization as well as how others perceived it. Ultimately, the rebranding effort failed; the only actual changes were the organization’s name and its personnel's uniforms. In fact, the Reforms seems to have contributed to even more corruption and abuse of power, as well an expansion of Law Enforcement’s ties to Corrupt Networks.

Keywords: bribery, corruption, moonlighting, police reform, Russia

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1469 High Throughput Virtual Screening against ns3 Helicase of Japanese Encephalitis Virus (JEV)

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

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1468 H.264 Video Privacy Protection Method Using Regions of Interest Encryption

Authors: Taekyun Doo, Cheongmin Ji, Manpyo Hong

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Like a closed-circuit television (CCTV), video surveillance system is widely placed for gathering video from unspecified people to prevent crime, surveillance, or many other purposes. However, abuse of CCTV brings about concerns of personal privacy invasions. In this paper, we propose an encryption method to protect personal privacy system in H.264 compressed video bitstream with encrypting only regions of interest (ROI). There is no need to change the existing video surveillance system. In addition, encrypting ROI in compressed video bitstream is a challenging work due to spatial and temporal drift errors. For this reason, we propose a novel drift mitigation method when ROI is encrypted. The proposed method was implemented by using JM reference software based on the H.264 compressed videos, and experimental results show the verification of our proposed methods and its effectiveness.

Keywords: H.264/AVC, video encryption, privacy protection, post compression, region of interest

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1467 The Active Subject and the Victim of Trafficking in Human Beings: Material and Procedural Criminal Law Approaches

Authors: Andrei Nastas, Sergiu Cernomopret

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This research addresses trafficking in human beings, in terms of the active subject and the victim of this crime, through the prism of national and international regulations in material and procedural criminal matters. For the correlative approach of both mentioned aspects, the active subject and the victim of trafficking in human beings, the research addresses both its constituent elements and the way to prevent and combat this phenomenon through criminal proceedings. As follows, trafficking in human beings, from a material criminal point of view, involves two subjects of this crime (active subject - offender and passive subject - victim), while their procedural status differs depending on the case (victim or injured party). The result of the research highlights some clarifications, which find a theoretical-practical basis in the legal provisions, the specialized doctrine, and the judicial practice.

Keywords: victim, active subject, abuse, injured party, crime

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1466 Chitosan Doped Curcumin Gold Clusters Flexible Nanofiber for Wound Dressing and Anticancer Activities

Authors: Saravanan Govindaraju, Kyusik Yun

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The purpose of this study is to develop the chitosan doped curcumin gold cluster nanofiber for wound healing and skin cancer drug delivery applications. Chitosan is a typical marine polysaccharide composed of glucosamine and n-acetyl glucosamine biodegradable and biocompatible polymer. Curcumin is a natural bioactive molecule obtained from Curcuma longo, it mostly occurs in some Asian countries like India and China. It has naturally antioxidant, antimicrobial, wound healing and anticancer property. Due to this advantage, we prepared a combination of natural polymer chitosan with Curcumin and gold nanocluster nanofiber (CH-CUR-AuNCs nanofibers). The prepared nanofiber was characterized by using Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). Antibacterial studies were performed with E.coli and S.aureus. Antioxidant assay, drug release test, and cytotoxicity will be evaluated. Prepared nanofiber emits low intensity of red fluorescent. The FTIR confirm the presence of chitosan and Curcumin in the nanofiber. In vitro study clearly shows the antibacterial activity against the gram negative and gram positive bacteria. Particularly, synthesised nanofibers provide better antibacterial activity against gram negative than gram positive. Cytotoxicity study also provides better killing rate in cancer cell, biocompatible with normal cell. Prepared CH-CUR-AuNCs nanofibers provide the better killing rate to bacterial strains and cancer cells. Finally, prepared nanofiber can be possible to use for wound healing dressing, patch for skin cancer and other biomedical applications.

Keywords: curcumin, chitosan, gold clusters, nanofibers

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1465 Psychosocial Predictors of Non-Suicidal Self-Injury in Adolescents: Literature Review

Authors: K. Grigoryan, T. Jurcik

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Interpersonal and school-related factors, along with individual characteristics, can predict non-suicidal self-injures (NSSI). The objective of this review is to describe psychosocial variables associated with NSSI among adolescents. A better understanding of this phenomenon may facilitate the identification of potentially effective interventions for adolescents. Relevant empirical studies and reviews from clinical, cross-cultural, and social psychology, as well as cognitive psychology literature, were synthesized into two broad topics: social/interpersonal and individual factors. Variables related to the occurrence of NSSI are discussed, including social support, peer modeling, abuse, personality traits, sense of belongingness, self-compassion, and others. Based on these findings, specific clinical recommendations were identified that need to be further evaluated empirically. The systemic interventions recommended in this review may further promote research in circumventing this social and clinical problem.

Keywords: non-suicidal self-injury, psychosocial factors, mental health, adolescence

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1464 Bionaut™: A Microrobotic Drug-Device Platform for the Local Treatment of Brainstem Gliomas

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

Abstract:

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

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1463 Towards Designing of a Potential New HIV-1 Protease Inhibitor Using Quantitative Structure-Activity Relationship Study in Combination with Molecular Docking and Molecular Dynamics Simulations

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

Abstract:

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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1462 Psychological Functioning of Youth Experiencing Community and Collective Violence in Post-conflict Northern Ireland

Authors: Teresa Rushe, Nicole Devlin, Tara O Neill

Abstract:

In this study, we sought to examine associations between childhood experiences of community and collective violence and psychological functioning in young people who grew up in post-conflict Northern Ireland. We hypothesized that those who grew up with such experiences would demonstrate internalizing and externalizing difficulties in early adulthood and, furthermore, that these difficulties would be mediated by adverse childhood experiences occurring within the home environment. As part of the Northern Ireland Childhood Adversity Study, we recruited 213 young people aged 18-25 years (108 males) who grew up in the post-conflict society of Northern Ireland using purposive sampling. Participants completed a digital questionnaire to measure adverse childhood experiences as well as aspects of psychological functioning. We employed the Adverse Childhood Experience -International Questionnaire (ACE-IQ¬) adaptation of the original Adverse Childhood Experiences Questionnaire (ACE) as it additionally measured aspects of witnessing community violence (e.g., seeing someone being beaten/killed, fights) and experiences of collective violence (e.g., war, terrorism, police, or gangs’ battles exposure) during the first 18 years of life. 51% of our sample reported experiences of community and/or collective violence (N=108). Compared to young people with no such experiences (N=105), they also reported significantly more adverse experiences indicative of household dysfunction (e.g., family substance misuse, mental illness or domestic violence in the family, incarceration of a family member) but not more experiences of abuse or neglect. As expected, young people who grew up with the community and/or collective violence reported significantly higher anxiety and depression scores and were more likely to engage in acts of deliberate self-harm (internalizing symptoms). They also started drinking and taking drugs at a younger age and were significantly more likely to have been in trouble with the police (externalizing symptoms). When the type of violence exposure was separated by whether the violence was witnessed (community violence) or more directly experienced (collective violence), we found community and collective violence to have similar effects on externalizing symptoms, but for internalizing symptoms, we found evidence of a differential effect. Collective violence was associated with depressive symptoms, whereas witnessing community violence was associated with anxiety-type symptoms and deliberate self-harm. However, when experiences of household dysfunction were entered into the models predicting anxiety, depression, and deliberate self-harm, none of the main effects remained significant. This suggests internalizing type symptoms are mediated by immediate family-level experiences. By contrast, significant community and collective violence effects on externalizing behaviours: younger initiation of alcohol use, younger initiation of drug use, and getting into trouble with the police persisted after controlling for family-level factors and thus are directly associated with growing up with the community and collective violence. Given the cross-sectional nature of our study, we cannot comment on the direction of the effect. However, post-hoc correlational analyses revealed associations between externalising behaviours and personal factors, including greater risk-taking and young age at puberty. The implications of the findings will be discussed in relation to interventions for young people and families living with the community and collective violence.

Keywords: community and collective violence, adverse childhood experiences, youth, psychological wellbeing

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1461 Identification of Vessel Class with Long Short-Term Memory Using Kinematic Features in Maritime Traffic Control

Authors: Davide Fuscà, Kanan Rahimli, Roberto Leuzzi

Abstract:

Preventing abuse and illegal activities in a given area of the sea is a very difficult and expensive task. Artificial intelligence offers the possibility to implement new methods to identify the vessel class type from the kinematic features of the vessel itself. The task strictly depends on the quality of the data. This paper explores the application of a deep, long short-term memory model by using AIS flow only with a relatively low quality. The proposed model reaches high accuracy on detecting nine vessel classes representing the most common vessel types in the Ionian-Adriatic Sea. The model has been applied during the Adriatic-Ionian trial period of the international EU ANDROMEDA H2020 project to identify vessels performing behaviors far from the expected one depending on the declared type.

Keywords: maritime surveillance, artificial intelligence, behavior analysis, LSTM

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1460 The Ameliorative Effects of the Histamine H3 Receptor Antagonist/Inverse Agonist DL77 on MK801-Induced Memory Deficits in Rats

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

Abstract:

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

Procedia PDF Downloads 155
1459 The Management of Care by People with Type 2 Diabetes versus the Professional Care at Primary Health Care in Brazil

Authors: Nunila Ferreira de Oliveira, Silvana Martins Mishima

Abstract:

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

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1458 Differential Expression Profile Analysis of DNA Repair Genes in Mycobacterium Leprae by qPCR

Authors: Mukul Sharma, Madhusmita Das, Sundeep Chaitanya Vedithi

Abstract:

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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1457 Treatment of Porphyromonas gingivalis Induced Gingivitis in Albino Rats with Tetracycline-Loaded Nanochitosan, an Immunohistochemical Analysis

Authors: Rania Hanafi Said, Rasha Mohamed Taha

Abstract:

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

Keywords: Immunohistochemistry, Nanochitosan, porphyromonas gingivitis, Tetracycline

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1456 Preparation and Optimization of Curcumin-HPβCD Complex Bioadhesive Vaginal Films for Vaginal Candidiasis by Factorial Design

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

Abstract:

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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1455 Preparation of Flurbiprofen Derivative for Enhanced Brain Penetration

Authors: Jungkyun Im

Abstract:

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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1454 Anti-Inflammatory and Analgesic Effects of Methanol Extract of Rhizophora racemosa Leaf in Albino Rats

Authors: Angalabiri-Owei E. Bekekeme, Brambaifa Nelson

Abstract:

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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1453 Resistance of Haemonchus spp. to Albendazole, Fenbendazole and Levamisole in 4 Goat Farms of Antioquia, Colombia

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

Abstract:

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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