Search results for: transdermal drug delivery system
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 19806

Search results for: transdermal drug delivery system

18816 Surface Characterization and Femtosecond-Nanosecond Transient Absorption Dynamics of Bioconjugated Gold Nanoparticles: Insight into the Warfarin Drug-Binding Site of Human Serum Albumin

Authors: Osama K. Abou-Zied, Saba A. Sulaiman

Abstract:

We studied the spectroscopy of 25-nm diameter gold nanoparticles (AuNPs), coated with human serum albumin (HSA) as a model drug carrier. The morphology and coating of the AuNPs were examined using transmission electron microscopy and dynamic light scattering. Resonance energy transfer from the sole tryptophan of HSA (Trp214) to the AuNPs was observed in which the fluorescence quenching of Trp214 is dominated by a static mechanism. Using fluorescein (FL) to probe the warfarin drug-binding site in HSA revealed the unchanged nature of the binding cavity on the surface of the AuNPs, indicating the stability of the protein structure on the metal surface. The transient absorption results of the surface plasmonic resonance (SPR) band of the AuNPs show three ultrafast dynamics that are involved in the relaxation process after excitation at 460 nm. The three decay components were assigned to the electron-electron (~ 400 fs), electron-phonon (~ 2.0 ps) and phonon-phonon (200–250 ps) interactions. These dynamics were not changed upon coating the AuNPs with HSA which indicates the chemical and physical stability of the AuNPs upon bioconjugation. Binding of FL in HSA did not have any measurable effect on the bleach recovery dynamics of the SPR band, although both FL and AuNPs were excited at 460 nm. The current study is important for a better understanding of the physical and dynamical properties of protein-coated metal nanoparticles which are expected to help in optimizing their properties for critical applications in nanomedicine.

Keywords: gold nanoparticles, human serum albumin, fluorescein, femtosecond transient absorption

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18815 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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18814 Web-Based Learning in Nursing: The Sample of Delivery Lesson Program

Authors: Merve Kadioğlu, Nevin H. Şahin

Abstract:

Purpose: This research is organized to determine the influence of the web-based learning program. The program has been developed to gain information about normal delivery skill that is one of the topics of nursing students who take the woman health and illness. Material and Methods: The methodology of this study was applied as pre-test post-test single-group quasi-experimental. The pilot study consisted of 28 nursing student study groups who agreed to participate in the study. The findings were gathered via web-based technologies: student information form, information evaluation tests, Web Based Training Material Evaluation Scale and web-based learning environment feedback form. In the analysis of the data, the percentage, frequency and Wilcoxon Signed Ranks Test were used. The Web Based Instruction Program was developed in the light of full learning model, Mayer's research-based multimedia development principles and Gagne's Instructional Activities Model. Findings: The average scores of it was determined in accordance with the web-based educational material evaluation scale: ‘Instructional Suitability’ 4.45, ‘Suitability to Educational Program’ 4.48, ‘Visual Adequacy’ 4.53, ‘Programming Eligibility / Technical Adequacy’ 4.00. Also, the participants mentioned that the program is successful and useful. A significant difference was found between the pre-test and post-test results of the seven modules (p < 0.05). Results: According to pilot study data, the program was rated ‘very good’ by the study group. It was also found to be effective in increasing knowledge about normal labor.

Keywords: normal delivery, web-based learning, nursing students, e-learning

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18813 The Methods of Immobilization of Laccase for Direct Transfer in an Enzymatic Fuel Cell

Authors: Afshin Farahbakhsh, Hoda Khodadadi

Abstract:

In this paper, we compare five methods of biological fuel cell fabrication by combining a Shewanella oneidensis microbial anode and a laccase-modified air-breathing cathode. As a result of biofuel cell laccase with graphite nanofibers, carbon surface (PAMAN) on the pt/hpg electrode, graphite sheets MWCNT and with (PG) and (MWCNT) showed, respectively. Describes methods for creating controllable and reproducible bio-anodes and demonstrates the versatility of hybrid biological fuel cells. The laccase-based biocathodes prepared either with the crude extract or with the purified enzyme can provide electrochemically active and stable biomaterials. The laccase-based biocathodes prepared either with the crude extract or with the purified enzyme can provide electrochemically active and stable biomaterials. When the device was fed with transdermal extracts, containing only 30μM of glucose, the average peak power was proportionally lower (0.004mW). The result of biofuel cell with graphite nanofibers showed the enzymatic fuel cell reaches 0.5 V at open circuit voltage with both, ethanol and methanol and the maximum current density observed for E2electrode was 228.94mAcm.

Keywords: enzymatic electrode, fuel cell, immobilization, laccase

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18812 Design and Implementation of 3kVA Grid-Tied Transformerless Power Inverter for Solar Photovoltaic Application

Authors: Daniel O. Johnson, Abiodun A. Ogunseye, Aaron Aransiola, Majors Samuel

Abstract:

Power Inverter is a very important device in renewable energy use particularly for solar photovoltaic power application because it is the effective interface between the DC power generator and the load or the grid. Transformerless inverter is getting more and more preferred to the power converter with galvanic isolation transformer and may eventually supplant it. Transformerless inverter offers advantages of improved DC to AC conversion and power delivery efficiency; and reduced system cost, weight and complexity. This work presents thorough analysis of the design and prototyping of 3KVA grid-tie transformerless inverter. The inverter employs electronic switching method with minimised heat generation in the system and operates based on the principle of pulse-width modulation (PWM). The design is such that it can take two inputs, one from PV arrays and the other from Battery Energy Storage BES and addresses the safety challenge of leakage current. The inverter system was designed around microcontroller system, modeled with Proteus® software for simulation and testing of the viability of the designed inverter circuit. The firmware governing the operation of the grid-tied inverter is written in C language and was developed using MicroC software by Mikroelectronica® for writing sine wave signal code for synchronization to the grid. The simulation results show that the designed inverter circuit performs excellently with very high efficiency, good quality sinusoidal output waveform, negligible harmonics and gives very stable performance under voltage variation from 36VDC to 60VDC input. The prototype confirmed the simulated results and was successfully synchronized with the utility supply. The comprehensive analyses of the circuit design, the prototype and explanation on overall performance will be presented.

Keywords: grid-tied inverter, leakage current, photovoltaic system, power electronic, transformerless inverter

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18811 Steady State Analysis of Distribution System with Wind Generation Uncertainity

Authors: Zakir Husain, Neem Sagar, Neeraj Gupta

Abstract:

Due to the increased penetration of renewable energy resources in the distribution system, the system is no longer passive in nature. In this paper, a steady state analysis of the distribution system has been done with the inclusion of wind generation. The modeling of wind turbine generator system and wind generator has been made to obtain the average active and the reactive power injection into the system. The study has been conducted on a IEEE-33 bus system with two wind generators. The present research work is useful not only to utilities but also to customers.

Keywords: distributed generation, distribution network, radial network, wind turbine generating system

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18810 Multi-Actors’ Scenario for Measuring Metropolitan Governance and Spatial Planning: A Case Study of Bangalore, India

Authors: H. S. Kumara

Abstract:

The rapid process of urbanization and the growing number of the metropolitan cities and its region call for better governance in India. This article attempts to argue that spatial planning really matters for measuring the governance at metropolitan scale. These study explore to metropolitan governance and spatial planning and its interrelationship issues, concepts and evolution of spatial planning in India and critically examines the multi actors’ scenario for measuring metropolitan governance by means of spatial planning in context with reviewing various master plans, concept of multi-actors viewpoint on role of spatial planning related to zoning regulations, master plan implementations and effective service delivery issues. This paper argues and concludes that the spatial planning of Bangalore directly impact on measuring metropolitan governance.

Keywords: metropolitan governance, spatial planning, service delivery, multi-actors’, opinion survey, master plan

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18809 Structure-Based Drug Design of Daptomycin, Antimicrobial lipopeptide

Authors: Satya Eswari Jujjavarapu, Swast Dhagat

Abstract:

Contagious diseases enact severe public health problems and have upsetting consequences. The cyclic lipopeptides explained by bacteria Bacillus, Paenibacillus, Pseudomonas, Streptomyces, Serratia, Propionibacterium and fungus Fusarium are very critical in confining the pathogens. As the degree of drug resistance upsurges in unparalleled manner, the perseverance of searching novel cyclic lipopeptides is being professed. The intense study has shown the implication of these bioactive compounds extending beyond antibacterial and antifungal. Lipopeptides, composed of single units of peptide and fatty acyl moiety, show broad spectrum antimicrobial effects. Among the surplus of cyclic lipopeptides, only few have materialized as strong antibiotics. For their functional vigor, polymyxin, daptomycin, surfactin, iturin and bacillomycin have been integrated in mainstream healthcare. In our work daptomycin has been a major part of antimicrobial resource since the past decade. Daptomycin, a cyclic lipopeptide consists of 13-member amino acid with a decanoyl side-chain. This structure of daptomycin confers it the mechanism of action through which it forms pore in the bacterial cell membrane resulting in the death of cell. Daptomycin is produced by Streptococccus roseoporus and acts against Streptococcus pneumonia (PSRP), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The PDB structure and ligands of daptomycin are available online. The molecular docking studies of these ligands with the lipopeptides were performed and their docking score and glide energy were recorded.

Keywords: daptomycin, molecular docking, structure-based drug design, lipopeptide

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18808 Characterization of PRL-3 Oncogenic Phosphatase in Its Role in Mediating Acquired Resistance to Bortezomib in Multiple Myeloma

Authors: Shamill Amedot Udonwa, Phyllis S. Y. Chong, Lim S. L. Julia, Wee-Joo Chng

Abstract:

In this paper, we investigated how PRL-3 expression in H929 and U266 cells affects the efficacy of drug treatment. H929 and U266 cells were treated with Bortezomib (BTZ) of different concentrations, and it was observed that H929 cells were resistant to BTZ, while U266 cells were not viable. Investigations into how BTZ targets these cells were conducted, and it was observed that BTZ affects the PARP-Caspase3 pathway as well as PRL-3-Leo1 pathways. These pathways regulate cell proliferation and cell cycle, respectively. Hence, we are able to show the mechanism of how BTZ affects cells and also the role PRL-3 plays on downstream oncogenes such as cyclin-D1 and c-MYC. More importantly, this investigation into PRL-3 in BTZ resistance will be highly applicable in the future as the first clinical trials of PRL-3 antibody (PRL3-zumab) are ongoing at the National University Hospital, Singapore (NUHS). This would mean that understanding the mechanism of resistance through PRL-3, which has yet to be studied, will demonstrate the potential of PRL-3 in developing novel strategies to improve the treatment of MM.

Keywords: drug resistance, hematology, multiple myeloma, oncogene

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18807 The Effect of Empathy Training Given to Midwives on Mothers’ Satisfaction with Midwives and Their Birth Perception

Authors: Songul Aktas, Turkan Pasinlioglu, Kiymet Yesilcicek Calik

Abstract:

Introduction: Emphatic approach during labor increases both quality of care and birth satisfaction of mothers. Besides; maternal satisfaction statements and expressions about midwives who assist labor contribute to a positive birth perception and wish to give vaginal delivery again. Aim: The study aimed at investigating the effect of empathy training given to midwives on mothers’ satisfaction with midwives and their birth perception. Material/Method: This experimental study was undertaken between February 2013 and January 2014 at a public hospital in Trabzon Province. The population of the study was composed of mothers who gave vaginal delivery and the sample was composed of 222 mothers determined with power analyzes. Ethical approval and written informed consents were obtained. Mothers who were assisted by midwives during 1st, 2nd and 3rd phases of delivery and first two postpartum hours were included. Empathy training given to midwives included didactic narration, creative drama, psychodrama techniques and lasted 32 hours. The data were collected before the empathy training (BET), right after empathy training (RAET) and 8 weeks later after birth (8WLAB). Mothers were homogenous in terms of socio-demographic, obstetric characteristics. Data were collected with a questionnaire and were analyzed with Chi-square tests. Findings: Rate of mother’s satisfaction with midwives was 36.5% in BET, 81.1% in RAET and 75.7% in 8WLAB. Key mother’s satisfaction with midwives were as follows: 27.6% of mothers told that midwives were “smiling-kind” in BET, 39.6% of them in RAET and 33.7% of them in 8WLAB; 31% of mothers told that midwives were “understanding” in BET, 38.2% of them in RAET and 33.7% of them in 8WLAB; 15.7% of mothers told that midwives were “reassuring” in BET, 44.9% of them in RAET and 39.3% of them in 8WLAB;19.5% of mothers told that midwives were “encouraging and motivating” in BET, 39.8% of them in RAET and 19.8% of mothers told that midwives were “informative” in BET, 45.6% of them in RAET and 35.1% of them in 8WLAB (p<0.05). Key mother’s dissatisfaction with midwives were as follows: 55.3% of mothers told that midwives were “poorly-informed” in BET, 17% of them in RAET and 27.7% of them in 8WLAB; 56.9% of mothers told that midwives were “poorly-listening” in BET, 17.6% of them in RAET and 25.5% of them in 8WLAB; 53.2% of mothers told that midwives were “judgmental-embarrassing” in BET, 17% of them in RAET and 29.8% of them in 8WLAB; 56.2% of mothers told that midwives had “fierce facial expressions” in BET, 15.6% of them in RAET and 28.1% of them in 8WLAB. Rates of mothers’ perception that labor was “easy” were 8.1% in BET, 21.6% in RAET and 13.5% in 8WLAB and rates of mothers’ perception that labor was “very difficult and tiring” were 41.9% in BET, 5.4% in RAET and 13.5% in 8WLAB (p<0.05). Conclusion: The effect of empathy training given to midwives upon statements that described mothers’ satisfaction with midwives and their birth perception was positive. Note: This study was financially funded by TUBİTAK project with number 113S672.

Keywords: empathy training, labor perception, mother’s satisfaction with midwife, vaginal delivery

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18806 Management Software for the Elaboration of an Electronic File in the Pharmaceutical Industry Following Mexican Regulations

Authors: M. Peña Aguilar Juan, Ríos Hernández Ezequiel, R. Valencia Luis

Abstract:

For certification, certain goods of public interest, such as medicines and food, it is required the preparation and delivery of a dossier. For its elaboration, legal and administrative knowledge must be taken, as well as organization of the documents of the process, and an order that allows the file verification. Therefore, a virtual platform was developed to support the process of management and elaboration of the dossier, providing accessibility to the information and interfaces that allow the user to know the status of projects. The development of dossier system on the cloud allows the inclusion of the technical requirements for the software management, including the validation and the manufacturing in the field industry. The platform guides and facilitates the dossier elaboration (report, file or history), considering Mexican legislation and regulations, it also has auxiliary tools for its management. This technological alternative provides organization support for documents and accessibility to the information required to specify the successful development of a dossier. The platform divides into the following modules: System control, catalog, dossier and enterprise management. The modules are designed per the structure required in a dossier in those areas. However, the structure allows for flexibility, as its goal is to become a tool that facilitates and does not obstruct processes. The architecture and development of the software allows flexibility for future work expansion to other fields, this would imply feeding the system with new regulations.

Keywords: electronic dossier, cloud management software, pharmaceutical industry, sanitary registration

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18805 Quoting Jobshops Due Dates Subject to Exogenous Factors in Developing Nations

Authors: Idris M. Olatunde, Kareem B.

Abstract:

In manufacturing systems, especially job shops, service performance is a key factor that determines customer satisfaction. Service performance depends not only on the quality of the output but on the delivery lead times as well. Besides product quality enhancement, delivery lead time must be minimized for optimal patronage. Quoting accurate due dates is sine quo non for job shop operational survival in a global competitive environment. Quoting accurate due dates in job shops has been a herculean task that nearly defiled solutions from many methods employed due to complex jobs routing nature of the system. This class of NP-hard problems possessed no rigid algorithms that can give an optimal solution. Jobshop operational problem is more complex in developing nations due to some peculiar factors. Operational complexity in job shops emanated from political instability, poor economy, technological know-how, and the non-promising socio-political environment. The mentioned exogenous factors were hardly considered in the previous studies on scheduling problem related to due date determination in job shops. This study has filled the gap created in the past studies by developing a dynamic model that incorporated the exogenous factors for accurate determination of due dates for varying jobs complexity. Real data from six job shops selected from the different part of Nigeria, were used to test the efficacy of the model, and the outcomes were analyzed statistically. The results of the analyzes showed that the model is more promising in determining accurate due dates than the traditional models deployed by many job shops in terms of patronage and lead times minimization.

Keywords: due dates prediction, improved performance, customer satisfaction, dynamic model, exogenous factors, job shops

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18804 Immuno-Protective Role of Mucosal Delivery of Lactococcus lactis Expressing Functionally Active JlpA Protein on Campylobacter jejuni Colonization in Chickens

Authors: Ankita Singh, Chandan Gorain, Amirul I. Mallick

Abstract:

Successful adherence of the mucosal epithelial cells is the key early step for Campylobacter jejuni pathogenesis (C. jejuni). A set of Surface Exposed Colonization Proteins (SECPs) are among the major factors involved in host cell adherence and invasion of C. jejuni. Among them, constitutively expressed surface-exposed lipoprotein adhesin of C. jejuni, JlpA, interacts with intestinal heat shock protein 90 (hsp90α) and contributes in disease progression by triggering pro-inflammatory response via activation of NF-κB and p38 MAP kinase pathway. Together with its ability to express in the bacterial surface, higher sequence conservation and predicted predominance of several B cells epitopes, JlpA protein reserves its potential to become an effective vaccine candidate against wide range of Campylobacter sps including C. jejuni. Given that chickens are the primary sources for C. jejuni and persistent gut colonization remain as major cause for foodborne pathogenesis to humans, present study explicitly used chickens as model to test the immune-protective efficacy of JlpA protein. Taking into account that gastrointestinal tract is the focal site for C. jejuni colonization, to extrapolate the benefit of mucosal (intragastric) delivery of JlpA protein, a food grade Nisin inducible Lactic acid producing bacteria, Lactococcus lactis (L. lactis) was engineered to express recombinant JlpA protein (rJlpA) in the surface of the bacteria. Following evaluation of optimal surface expression and functionality of recombinant JlpA protein expressed by recombinant L. lactis (rL. lactis), the immune-protective role of intragastric administration of live rL. lactis was assessed in commercial broiler chickens. In addition to the significant elevation of antigen specific mucosal immune responses in the intestine of chickens that received three doses of rL. lactis, marked upregulation of Toll-like receptor 2 (TLR2) gene expression in association with mixed pro-inflammatory responses (both Th1 and Th17 type) was observed. Furthermore, intragastric delivery of rJlpA expressed by rL. lactis, but not the injectable form, resulted in a significant reduction in C. jejuni colonization in chickens suggesting that mucosal delivery of live rL. lactis expressing JlpA serves as a promising vaccine platform to induce strong immune-protective responses against C. jejuni in chickens.

Keywords: chickens, lipoprotein adhesion of Campylobacter jejuni, immuno-protection, Lactococcus lactis, mucosal delivery

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18803 Detection of Fuel Theft and Vehicle Position Using Third Party Monitoring Software

Authors: P. Senthilraja, C. Rukumani Khandhan, M. Palaniappan, S. L. Rama, P. Sai Sushimitha, R. Madhan, J. Vinumathi, N. Vijayarangan

Abstract:

Nowadays, the logistics achieve a vast improvement in efficient delivery of goods. The technology improvement also helps to improve its development, but still the owners of transport vehicles face problems, i.e., fuel theft in vehicles by the drivers or by an unknown person. There is no proper solution to overcome the problems. This scheme is to determine the amount of fuel that has been stolen and also to determine the position of the vehicle at a particular time using the technologies like GPS, GSM, ultrasonic fuel level sensor and numeric lock system. The ultrasonic sensor uses the ultrasonic waves to calculate the height of the tank up to which the fuel is available. Based on height it is possible to calculate the amount of fuel. The Global Positioning System (GPS) is a satellite-based navigation system. The scientific community uses GPS for its precision timing capability and position information. The GSM provides the periodic information about the fuel level. A numeric lock system has been provided for fuel tank opening lever. A password is provided to access the fuel tank lever and this is authenticated only by the driver and the owner. Once the fuel tank is opened an alert is sent to owner through a SMS including the timing details. Third party monitoring software is a user interface that updates the information automatically into the database which helps to retrieve the data as and when required. Third party monitoring software provides vehicle’s information to the owner and also shows the status of the vehicle. The techniques that are to be proposed will provide an efficient output. This project helps to overcome the theft and hence to put forth fuel economy.

Keywords: fuel theft, third party monitoring software, bioinformatics, biomedicine

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18802 How Information Sharing Can Improve Organizational Performance?

Authors: Syed Abdul Rehman Khan

Abstract:

In today’s world, information sharing plays a vital role in successful operations of supply chain; and boost to the profitability of the organizations (end-to-end supply chains). Many researches have been completed over the role of information sharing in supply chain. In this research article, we will investigate the ‘how information sharing can boost profitability & productivity of the organization; for this purpose, we have developed one conceptual model and check to that model through collected data from companies. We sent questionnaire to 369 companies; and will filled form received from 172 firms and the response rate was almost 47%. For the data analysis, we have used Regression in (SPSS software) In the research findings, our all hypothesis has been accepted significantly and due to the information sharing between suppliers and manufacturers ‘quality of material and timely delivery’ increase and also ‘collaboration & trust’ will become more stronger and these all factors will lead to the company’s profitability directly and in-directly. But unfortunately, companies could not avail the all fruitful benefits of information sharing due to the fear of ‘compromise confidentiality or leakage of information’.

Keywords: collaboration, information sharing, risk factor, timely delivery

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18801 Clinical Staff Perceptions of the Quality of End-of-Life Care in an Acute Private Hospital: A Mixed Methods Design

Authors: Rosemary Saunders, Courtney Glass, Karla Seaman, Karen Gullick, Julie Andrew, Anne Wilkinson, Ashwini Davray

Abstract:

Current literature demonstrates that most Australians receive end-of-life care in a hospital setting, despite most hoping to die within their own home. The necessity for high quality end-of-life care has been emphasised by the Australian Commission on Safety and Quality in Health Care and the National Safety and Quality in Health Services Standards depict the requirement for comprehensive care at the end of life (Action 5.20), reinforcing the obligation for continual organisational assessment to determine if these standards are suitably achieved. Limited research exploring clinical staff perspectives of end-of-life care delivery has been conducted within an Australian private health context. This study aimed to investigate clinical staff member perceptions of end-of-life care delivery at a private hospital in Western Australia. The study comprised of a multi-faceted mixed-methods methodology, part of a larger study. Data was obtained from clinical staff utilising surveys and focus groups. A total of 133 questionnaires were completed by clinical staff, including registered nurses (61.4%), enrolled nurses (22.7%), allied health professionals (9.9%), non-palliative care consultants (3.8%) and junior doctors (2.2%). A total of 14.7% of respondents were palliative care ward staff members. Additionally, seven staff focus groups were conducted with physicians (n=3), nurses (n=26) and allied health professionals including social workers (n=1), dietitians (n=2), physiotherapists (n=5) and speech pathologists (n=3). Key findings from the surveys highlighted that the majority of staff agreed it was part of their role to talk to doctors about the care of patients who they thought may be dying, and recognised the importance of communication, appropriate training and support for clinical staff to provide quality end-of-life care. Thematic analysis of the qualitative data generated three key themes: creating the setting which highlighted the importance of adequate resourcing and conducive physical environments for end-of-life care and to support staff and families; planning and care delivery which emphasised the necessity for collaboration between staff, families and patients to develop care plans and treatment directives; and collaborating in end-of-life care, with effective communication and teamwork leading to achievable care delivery expectations. These findings contribute to health professionals better understanding of end-of-life care provision and the importance of collaborating with patients and families in care delivery. It is crucial that health care providers implement strategies to overcome gaps in care, so quality end-of-life care is provided. Findings from this study have been translated into practice, with the development and implementation of resources, training opportunities, support networks and guidelines for the delivery of quality end-of-life care.

Keywords: clinical staff, end-of-life care, mixed-methods, private hospital.

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18800 Tuberculosis in Humans and Animals in the Eastern Part of the Sudan

Authors: Yassir Adam Shuaib, Stefan Niemann, Eltahir Awad Khalil, Ulrich Schaible, Lothar Heinz Wieler, Mohammed Ahmed Bakhiet, Abbashar Osman Mohammed, Mohamed Abdelsalam Abdalla, Elvira Richter

Abstract:

Tuberculosis (TB) is a chronic bacterial disease of humans and animals and it is characterized by the progressive development of specific granulomatous tubercle lesions in affected tissues. In a six-month study, from June to November 2014, a total of 2,304 carcasses of cattle, camel, sheep, and goats slaughtered at East and West Gaash slaughterhouses, Kassala, were investigated during postmortem, in parallel, 101 sputum samples from TB suspected patients at Kassala and El-Gadarif Teaching Hospitals were collected in order to investigate tuberculosis in animals and humans. Only 0.1% carcasses were found with suspected TB lesions in the liver and lung and peritoneal cavity of two sheep and no tuberculous lesions were found in the carcasses of cattle, goats or camels. All samples, tissue lesions and sputum, were decontaminated by the NALC-NaOH method and cultured for mycobacterial growth at the NRZ for Mycobacteria, Research Center Borstel, Germany. Genotyping and molecular characterization of the grown strains were done by line probe assay (GenoType CM and MTBC) and 16S rDNA, rpoB gene, and ITS sequencing, spoligotyping, MIRU-VNTR typing and next generation sequencing (NGS). Culture of the specimens revealed growth of organisms from 81.6% of all samples. Mycobacterium tuberculosis (76.2%), M. intracellulare (14.2%), mixed infection with M. tuberculosis and M. intracellulare (6.0%) and mixed infection with M. tuberculosis and M. fortuitum and with M. intracellulare and unknown species (1.2%) were detected in the sputum samples and unknown species (1.2%) were detected in the samples of one of the animals tissues. From the 69 M. tuberculosis strains, 25 (36.2%) were showing either mono-drug-resistant or multi-drug-resistant or poly-drug-resistant but none was extensively drug-resistant. In conclusion, the prevalence of TB in animals was very low while in humans M. tuberculosis-Delhi/CAS lineage was responsible for most cases and there was an evidence of MDR transmission and acquisition.

Keywords: animal, human, slaughterhouse, Sudan, tuberculosis

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18799 Way to Successful Enterprise Resource Planning System Implementation in Developing Countries: Case of Public Sector Unit

Authors: Suraj Kumar Mukti

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Enterprise Resource Planning (ERP) system is a management tool to integrate all departments in an organization. It integrates business processes, manages resources efficiently and provides an appropriate decision support system to management. ERP system implementation is a typical and time taking process as well as money consuming process. Articles related to key success factors of ERP system implementation are available in the literature, but rare authors have focused on roadmap of successful ERP system implementation. Postponement is better if the organization is not ready to implement ERP system in better way; hence checking of organization’s preparation to adopt new system is an important prerequisite to ensure the success of ERP system implementation in an organization. Then comes what will be called as success of ERP system implementation. Benefits achieved by ERP system may be categorized into two categories; viz. tangible and intangible benefits. This research article presents a roadmap to ensure the success of ERP system implementation and benefits achieved through the new system as in success indicator. A case study is presented to evaluate the success and benefit achieved through the new system. The article gives a comprehensive approach to academicians and a roadmap to the organizations seeking to implement the ERP system.

Keywords: ERP system, decision support system, tangible, intangible

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18798 Increasing Toughness of Oriented Polyvinyl Alcohol (PVA)/Fe3O4 Nanocomposite

Authors: Mozhgan Chaichi, Farhad Sharif, Saeede Mazinani

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Polymer nanocomposites are a new class of materials for fabricating future multifunctional and lightweight structures. To obtain good mechanical, thermal and electrical properties, it is essential to achieve uniform dispersion of nanoparticles in polymer matrix. Alignment of nanoparticles in matrix can enhance mechanical, thermal, electrical and barrier properties of nanocomposites in oriented direction. Fe3O4 nanoparticles have generated huge activity in many areas of science and engineering due to its magnetic properties. Magnetic nanoparticles have been investigated for a wide range of applications in sensors, magnetic energy storage, environmental remediation, heterogeneous catalysts and drug delivery. The magnetic response from the Fe3O4 nanoparticles can facilitate with the alignment of nanofillers in a polymer matrix under magnetic field, aiming at fabricating composites with directional properties and functions. Here we report oriented nanocomposites based on Fe3O4 nanoparticles and poly (vinyl alcohol) (PVA), which prepared via a facile aqueous solution by applying a low external magnetic field (750 G). A significant enhancement of mechanical properties, and especially toughness of nanofilms, of oriented PVA/ Fe3O4 nanocomposites is obtained at low nanoparticles loading. Orientation of nanoparticles can align polymer chains and enhance mechanical properties. For example, orientation of 0.1 wt. % Fe3O4 nanoparticles increase 31% toughness and 23% modulus of oriented nanocomposite in compare of pure films, which indicate good dispersion of nanoparticles and efficient load transfer between nanoparticles and matrix.

Keywords: magnetic nanoparticles, nanocomposites, toughness, orientation

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18797 Design and Facile Synthesis of New Amino Acid Derivatives with Anti-Tumor and Antimicrobial Activities

Authors: Hoda Sabry Othman, Randa Helmy Swellem, Galal Abd El-Moein Nawwar

Abstract:

N-cyanoacetyl glycine is a reactive polyfunctional precursor for synthesis of new difficult accessible compounds including pyridones, thiazolopyridine and others. The key step of this protocol is the formation of different ylidines which underwent Michael addition with carbon nucleophiles affording various heterocyclic compounds. Selected compounds underwent pharmacological evaluation, in vitro against two cell lines; breast cell line (MCF-7),and liver cell line(HEPG2). Compounds 14, 15a and 16 showed IC50 values 8.93, 8.18 and 8.03 (µ/ml) respectively for breast cell line (MCF-7), while the standard drug (Tamoxifen) revealed IC50 8.31. With respect to the liver cell line (HEPG2), compounds 14 and 15a revealed IC50 18.4 and 13.6(µ/ml) respectively while the IC50 of the standard drug(5-Flurouracil) is 25(µ/ml). The antimicrobial activity was also screened and revealed that oxime 7 and ylidine 9f showed a broad-spectrum activity.

Keywords: antitumor, cyanoacetyl glycine, heterocycles, pyridones

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18796 A pH-Activatable Nanoparticle Self-Assembly Triggered by 7-Amino Actinomycin D Demonstrating Superior Tumor Fluorescence Imaging and Anticancer Performance

Authors: Han Xiao

Abstract:

The development of nanomedicines has recently achieved several breakthroughs in the field of cancer treatment; however, the biocompatibility and targeted burst release of these medications remain a limitation, which leads to serious side effects and significantly narrows the scope of their applications. The self-assembly of intermediate filament protein (IFP) peptides was triggered by a hydrophobic cation drug 7-amino actinomycin D (7-AAD) to synthesize pH-activatable nanoparticles (NPs) that could simultaneously locate tumors and produce antitumor effects. The designed IFP peptide included a target peptide (arginine–glycine–aspartate), a negatively charged region, and an α-helix sequence. It also possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step method. 7-AAD molecules with excellent near-infrared fluorescence properties could be target delivered into tumor cells by NPs and released immediately in the acidic environments of tumors and endosome/lysosomes, ultimately inducing cytotoxicity by arresting the tumor cell cycle with inserted DNA. It is noteworthy that the IFP/7-AAD NPs tail vein injection approach demonstrated not only high tumor-targeted imaging potential, but also strong antitumor therapeutic effects in vivo. The proposed strategy may be used in the delivery of cationic antitumor drugs for precise imaging and cancer therapy.

Keywords: 7-amino actinomycin D, intermediate filament protein, nanoparticle, tumor image

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18795 Association of Genetically Proxied Cholesterol-Lowering Drug Targets and Head and Neck Cancer Survival: A Mendelian Randomization Analysis

Authors: Danni Cheng

Abstract:

Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

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18794 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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18793 Development of Extemporaneous Pediatric Syrup of Prednisone

Authors: Amel Chenafa, Sihem Boulenouar, Linda Aoued, Imane Sediri, Ismahan Djebbar, Mohamed Adil Selka

Abstract:

Introduction: The specialties intended for adults are often inadequate marketed for pediatric use, such as for a galenic form or in the dosage. For an industrial, development of a pediatric drug is confronted to various problems. So, the hospital pharmacies have to respond to adaptation needs of pharmaceutical forms for pediatric use. The objective of our work is to develop an oral form of prednisone for pediatric use since no adapted form to children is commercialized. Materials and Methods: Therefore an extemporaneous syrup of prednisone was prepared at the concentration of 0,5mg/ml from 5mg tablets and stored in amber glass bottles. Organoleptic and microbiological stability was studied in two temperatures: 5°C and 25°C, and evaluated at D0, D15, and D30. Results: No organoleptic changes have been detected on the syrup conserved at 25 and 5°C. The results show that there is no presence of bacteria, yeasts, and molds in the syrups stored at both temperatures during the analysis period. Conclusion: Sheltered from light, the developed syrup of prednisone remained stable at room temperature and/or refrigerator for 30 days.

Keywords: extemporaneous syrup, pediatric drug, prednisone, stability

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18792 Maternal Health Care Mirage: A Study of Maternal Health Care Utilization for Young Married Muslim Women in India

Authors: Saradiya Mukherjee

Abstract:

Background: Indian Muslims, compared to their counterparts in other religions, generally do not fare well on many yardsticks related to socio-economic progress and the same is true with maternal health care utilization. Due to low age at marriage a major percentage of child birth is ascribed to young (15-24 years) Muslim mothers in, which pose serious concerns on the maternal health care of Young Married Muslim women (YMMW). A thorough search of past literature on Muslim women’s health and health care reveals that studies in India have mainly focused on religious differences in fertility levels and contraceptive use while the research on the determinants of maternal health care utilization among Muslim women are lacking in India. Data and Methods: Retrieving data from the National Family Health Survey -3 (2005-06) this study attempts to assess the level of utilization and factors effecting three key maternal health indicators (full ANC, safe delivery and PNC) among YMMW (15-24 years) in India. The key socio-economic and demographic variables taken as independent or predictor variables in the study was guided by existing literature particularly for India. Bi-variate analysis and chi square test was applied and variables which were found to be significant were further included in binary logistic regression. Results: The findings of the study reveal abysmally low levels of utilization for all three indicators i.e. full ANC, safe delivery and PNC of maternal health care included in the study. Mother’s education, mass media exposure, women’s autonomy, birth order, economic status wanted status of child and region of residence were found to be significant variables effecting maternal health care utilization among YMMW. Multivariate analysis reveals that no mass media exposure, lower autonomy, education, poor economic background, higher birth order and unintended pregnancy are some of the reasons behind low maternal health care utilization. Conclusion: Considering the low level of safe maternal health care utilization and its proximate determinants among YMMW the study suggests educating Muslim girls, promoting family planning use, involving media and collaboration between religious leader and health care system could be some important policy level interventions to address the unmet need of maternity services among YMMW.

Keywords: young Muslim women, religion, socio-economic condition, antenatal care, delivery, post natal care

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18791 The Disease That 'Has a Woman Face': Feminization of HIV/AIDS in Nagaland, North-East India

Authors: Kitoholi V. Zhimo

Abstract:

Unlike the cases of cases of homosexuals, haemophilic and or drug users in USA, France, Africa and other countries, in India the first case of HIV/AIDS was detected in heterosexual female sex workers (FSW) in Chennai in 1986. This image played an important role in understanding HIV/AIDS scenario in the country. Similar to popular and dominant metaphors on HIV/AIDS such as ‘gay plague’, ‘new cancer’, ‘lethal disease’, ‘slim disease’, ‘foreign disease’, ‘junkie disease’, etc. around the world, the social construction of the virus was largely attributed to women in India. It was established that women particularly sex workers are ‘carrier’ and ‘transmitter’ of virus and were categorised as High Risk Groups (HRG’s) alongside homosexuals, transgenders and injecting drug users. Recent literature reveals growing rate of HIV infection among housewives since 1997 which revolutionised public health scenario in India. This means shift from high risk group to general public through ‘bridge population’ encompassing long distance truckers and migrant labours who at the expense of their nature of work and mobility comes in contact with HRG’s and transmit the virus to the general public especially women who are confined to the domestic space. As HIV epidemic expands, married women in monogamous relationship/marriage stand highly susceptible to infection with limited control, right and access over their sexual and reproductive health and planning. In context of Nagaland, a small state in North-eastern part of India HIV/AIDS transmission through injecting drug use dominated the early scene of the epidemic. However, paradigm shift occurred with declining trend of HIV prevalence among injecting drug users (IDU’s) over the past years with the introduction of Opioid Substitution Therapy (OST) and easy access/availability of syringes and injecting needles. Reflection on statistical data reveals that out of 36 states and union territories in India, the position of Nagaland in HIV prevalence among IDU’s has significantly dropped down from 6th position in 2003 to 16th position in 2017. The present face of virus in Nagaland is defined by (hetero) sexual mode of transmission which accounts for about 91% of as reported by Nagaland state AIDS control society (NSACS) in 2016 wherein young and married woman were found to be most affected leading to feminization of HIV/AIDS epidemic in the state. Thus, not only is HIV epidemic feminised but emerged victim to domestic violence which is more often accepted as normal part of heterosexual relationship. In the backdrop of these understanding, the present paper based on ethnographic fieldwork explores the plight, lived experiences and images of HIV+ve women with regard to sexual and reproductive rights against the backdrop of patriarchal system in Nagaland.

Keywords: HIV/AIDS, monogamy, Nagaland, sex worker disease, women

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18790 Impect of Human on Prey of Birds in North West Rajasthan

Authors: Dau Lal Bohra, Sradha Vyas

Abstract:

Bird species are already showing climate-related changes in the dates they migrate and breed, and in the timing of other key life-history events. Treats of feeding managements raptors have performed important ecological, traditional and aesthetic functions throughout the Indian subcontinent. The declines in India result from elevated adult and juvenile mortality, and low breeding success. The widespread and rapid pattern of declines, i.e. in all areas irrespective of habitat or protection status suggest that persecution through shooting or poisoning, whilst important at a local scale, are unlikely to have caused the declines. A mass killing of several species of vultures in the Indian subcontinent over the last two decades is largely blamed on the presence of a drug. Veterinary diclofenac caused an unprecedented decline in South Asia’s Gyps vulture populations, with some species declining by more than 97% between 1992 and 2007. Veterinary diclofenac causes renal failure in vultures, and killed tens of millions of such birds in the Indian sub-continent. The drug was finally banned there for veterinary purposes in 2006. This drug is now ‘a global problem’ threatening many vulnerable birds of prey. Recently, stappe eagles are also susceptible to veterinary diclofenac, effectively increasing the potential threat level, and the risks for European biodiversity. Steppe eagles are closely related with golden eagles (Aquila chrysaetus), imperial eagles (Aquila heliaca) and Spanish imperial eagles (Aquila adalberti), and all these species scavenge opportunistically on carcasses throughout their range. The Spanish imperial eagle, considered Vulnerable at global level, is now particularly at risk, due to the availability of diclofenac in Spain. These findings strengthen the case for banning veterinary diclofenac across. From year 2011 to 2014 more than 300 hundred birds dead in jorbeer, Bikaner. Now, with unequivocal evidence that this veterinary drug can cause a much wider impact on Europe´s biodiversity, it is time for action – please ban diclofenac human brand also in multi-dose vial from market.

Keywords: mortility, prey of birds, diclofenac, Rajasthan

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18789 Formulation and In vivo Evaluation of Venlafaxine Hydrochloride Long Acting Tablet

Authors: Abdulwahhab Khedr, Tamer Shehata, Hanaa El-Ghamry

Abstract:

Venlafaxine HCl is a novel antidepressant drug used in the treatment of major depressive disorder, generalized anxiety disorder, social anxiety disorder and panic disorder. Conventional therapeutic regimens with venlafaxine HCl immediate-release dosage forms require frequent dosing due to short elimination half-life of the drug and reduced bioavailability. Hence, this study was carried out to develop sustained-release dosage forms of venlafaxine HCl to reduce its dosing frequency, to improve patient compliance and to reduce side effects of the drug. The polymers used were hydroxypropylmethyl cellulose, xanthan gum, sodium alginate, sodium carboxymethyl cellulose, Carbopol 940 and ethyl cellulose. The physical properties of the prepared tablets including tablet thickness, diameter, weight uniformity, content uniformity, hardness and friability were evaluated. Also, the in-vitro release of venlafaxine HCl from different matrix tablets was studied. Based on physical characters and in-vitro release profiles, certain formulae showing promising sustained-release profiles were subjected to film coating with 15% w/v EC in dichloromethane/ethanol mixture (1:1 ratio) using 1% w/v HPMC as pore former and 30% w/w dibutyl phthalate as plasticizer. The optimized formulations were investigated for drug-excipient compatibility using FTIR and DSC studies. Physical evaluation of the prepared tablets fulfilled the pharmacopoeial requirements for tablet friability test, where the weight loss of the prepared formulae did not exceed 1% of the weight of the tested tablets. Moderate release was obtained from tablets containing HPMC. FTIR and DSC studies for such formulae revealed the absence of any type of chemical interaction between venlafaxine HCl and the used polymers or excipients. Forced swimming test in rats was used to evaluate the antidepressant activity of the selected matrix tablets of venlafaxine HCl. Results showed that formulations significantly decreased the duration of animals’ immobility during the 24 hr-period of the test compared to non-treated group.

Keywords: antidepressant, sustained-release, matrix tablet, venlafaxine hydrochloride

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18788 Review of Capitalization of Construction Industry on Sustainable Risk Management in Nigeria

Authors: Nnadi Ezekiel Ejiofor

Abstract:

The construction industry plays a decisive role in the healthy development of any nation. Not only large but even small construction projects contribute to a country’s economic growth. There is a need for good management to ensure successful delivery and sustainability because of the plethora of risks that have resulted in low-profit margins for contractors, cost and schedule overruns, poor quality delivery, and abandoned projects. This research reviewed Capitalization on Sustainable Risk Management. Questionnaires and oral interviews conducted were utilized as means of data collection. One hundred and ninety-eight (198) large construction firms in Nigeria form the population of this study. 15 (fifteen) companies that emanated from merger and acquisition were used for the study. The instruments used for data collection were a researcher-developed structured questionnaire based on a five-point rating scale, interviews, focus group discussion, and secondary sources (bill of quantities and stock and exchange commission). The instrument was validated by two experts in the field. The reliability of the instrument was established by applying the split-half method. Kendall’s coefficient of concordance was used to test the data, and a degree of agreement was obtained. Data were subjected to descriptive statistics and analyzed using analysis of variance, t-test, and SPSS. The identified impacts of capitalization were an increase in turnover (24.5%), improvement in the image (24.5%), risk reduction (20%), business expansion (17.3%), and geographical spread (13.6%). The study strongly advocates the inclusion of risk management evaluation as part of the construction procurement process.

Keywords: capitalization, project delivery, risks, risk management, sustainability

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18787 The Optimization of Topical Antineoplastic Therapy Using Controlled Release Systems Based on Amino-functionalized Mesoporous Silica

Authors: Lacramioara Ochiuz, Aurelia Vasile, Iulian Stoleriu, Cristina Ghiciuc, Maria Ignat

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Topical administration of chemotherapeutic agents (eg. carmustine, bexarotene, mechlorethamine etc.) in local treatment of cutaneous T-cell lymphoma (CTCL) is accompanied by multiple side effects, such as contact hypersensitivity, pruritus, skin atrophy or even secondary malignancies. A known method of reducing the side effects of anticancer agent is the development of modified drug release systems using drug incapsulation in biocompatible nanoporous inorganic matrices, such as mesoporous MCM-41 silica. Mesoporous MCM-41 silica is characterized by large specific surface, high pore volume, uniform porosity, and stable dispersion in aqueous medium, excellent biocompatibility, in vivo biodegradability and capacity to be functionalized with different organic groups. Therefore, MCM-41 is an attractive candidate for a wide range of biomedical applications, such as controlled drug release, bone regeneration, protein immobilization, enzymes, etc. The main advantage of this material lies in its ability to host a large amount of the active substance in uniform pore system with adjustable size in a mesoscopic range. Silanol groups allow surface controlled functionalization leading to control of drug loading and release. This study shows (I) the amino-grafting optimization of mesoporous MCM-41 silica matrix by means of co-condensation during synthesis and post-synthesis using APTES (3-aminopropyltriethoxysilane); (ii) loading the therapeutic agent (carmustine) obtaining a modified drug release systems; (iii) determining the profile of in vitro carmustine release from these systems; (iv) assessment of carmustine release kinetics by fitting on four mathematical models. Obtained powders have been described in terms of structure, texture, morphology thermogravimetric analysis. The concentration of the therapeutic agent in the dissolution medium has been determined by HPLC method. In vitro dissolution tests have been done using cell Enhancer in a 12 hours interval. Analysis of carmustine release kinetics from mesoporous systems was made by fitting to zero-order model, first-order model Higuchi model and Korsmeyer-Peppas model, respectively. Results showed that both types of highly ordered mesoporous silica (amino grafted by co-condensation process or post-synthesis) are thermally stable in aqueous medium. In what regards the degree of loading and efficiency of loading with the therapeutic agent, there has been noticed an increase of around 10% in case of co-condensation method application. This result shows that direct co-condensation leads to even distribution of amino groups on the pore walls while in case of post-synthesis grafting many amino groups are concentrated near the pore opening and/or on external surface. In vitro dissolution tests showed an extended carmustine release (more than 86% m/m) both from systems based on silica functionalized directly by co-condensation and after synthesis. Assessment of carmustine release kinetics revealed a release through diffusion from all studied systems as a result of fitting to Higuchi model. The results of this study proved that amino-functionalized mesoporous silica may be used as a matrix for optimizing the anti-cancer topical therapy by loading carmustine and developing prolonged-release systems.

Keywords: carmustine, silica, controlled, release

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