Search results for: drug delivery
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3407

Search results for: drug delivery

797 Spawning Induction and Early Larval Development of the Giant Reef Clam Periglypta multicostata (Sowerby, 1835) under Controlled Conditions

Authors: Jose Melena, Rosa Santander, Tanya Gonzalez, Richard Duque, Juan Illanes

Abstract:

Ecuador is one of the countries with the greatest aquatic biodiversity worldwide. In particular, there are at least a dozen native marine species with great aquaculture potential locally. This research concerns one of those species. It has proposed to implement experimental protocols in order to induce spawning and to generate the early larval development of the giant reef clam P. multicostata under controlled conditions. Bioassays were carried out with one adult batch (n= 8) with an average valvar length of 118,4 ± 5,8 mm, which were collected near of the Puerto Santa Rosa (2° 12' 30'' S, 80° 58' 28'' W), Santa Elena Province. During a short acclimation stage, the eight adults of giant reef clam P. multicostata were exposed to thermal stress. Briefly, the experimental protocol for spawning induction was based on the application of 20°C for 1 h and 30°C for 1 h on P. multicostata broodstock at least three consecutive times by one day. After spawning, collected sexual material was released for external fertilization process. After the delivery of gametes, it was achieved 3,25 × 10⁶ viable zygotes. As results, fertilized eggs had 56 µm diameter; while first and second cell divisions were observed to 2,5 h post-fertilization, with individual average length of 68 ± 5 µm and polar body. Latter cell divisions, including gastrula stage, appeared at 9 h post-fertilization, with individual average length of 73 ± 4 µm and trochophore stage at 15 h post-fertilization with individual average length of 75 ± 4 µm. In addition, veliger stage was registered at 20 h post-fertilization with individual average length of 82 ± 6 µm. Umboned larvae appeared at day 8 post-fertilization, with individual average length of 148 ± 6 µm. These pioneering results worldwide can strengthen the local conservation process of the overexploited P. multicostata and to encourage its production for commercial purposes.

Keywords: Ecuador, larval development, Periglypta multicostata, spawning induction

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796 Public and Private Involvement in Agricultural Extension Services: Factors of Farmers’ Preference in Southwestern Nigeria

Authors: S. O. Ayansina, O. A. Adekunle

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There is an increasing demand for a functional extension delivery services in Nigeria with a view to meet up with the food and fiber needs of the ever growing population of human and animal respectively. The study was therefore designed to examine the farmers’ preference for public and private extension services in Southwestern Nigeria, specifically to determine the farmers’ level of participation in the two types of organizations involved and also to evaluate the Performance level of personnel in the two organizations in order to ascertain the beneficiaries’ satisfaction. A multi-stage random sampling technique was used to samples 30 respondents from each of the three selected organizations in each of the three states sampled in Southwestern Nigeria. Hence, 270 respondents were sampled for the study. Data collected were analyzed with Kruskal Wallis one-way Analysis of variance to test the difference between the participation of beneficiaries in the public and private extension services and the level of benefit accrued from the two organizations involved in the study. Results generally revealed that private organizations were performing better and were more preferred by the beneficiaries. Results of the tested hypotheses as shown by Kruskal Wallis test of difference (x2=0.709) indicates no significant difference between farmers’ participation in the extension services of public and private organizations but however shows significant difference (X2=12.074) in the benefits achieved by respondents in the two organizations, such benefits include: increased quantity of Crop produced, farm income, skill acquisition, and improved Education in private extension organizations. Based on this result, it could be inferred that beneficiaries generally preferred private extension organizations because of their effectiveness and vibrancy in programme administration. Public extension is therefore recommended for general overhauling and possibly “merging” of public and private sectors in order to cater for teeming population of farmers demanding for efficient and functional extension services to better their lots both in production and processing.

Keywords: public and private involvement, extension services, farmers’ preferences, Kruskal Wallis Test

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795 Synthesis and Characterization of Heterogeneous Silver Nanoparticles for Protection of Ancient Egyptian Artifacts from Microbial Deterioration

Authors: Mohamed Abd Elfattah Ibraheem Elghrbawy

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Biodeterioration of cultural heritage is a complex process which is caused by the interaction of many physical, chemical and biological agents; the growth of microorganisms can cause staining, cracking, powdering, disfigurement and displacement of monuments material, which leads to the permanent loss of monuments material. Organisms causing biodeterioration on monuments have usually been controlled by chemical products (biocides). In order to overcome the impact of biocides on the environment, human health and monument substrates, alternative tools such as antimicrobial agents from natural products can be used for monuments conservation and protection. The problem is how to formulate antibacterial agents with high efficiency and low toxicity. Various types of biodegradable metal nanoparticles (MNPs) have many applications in plant extract delivery. So, Nano-encapsulation of metal and natural antimicrobial agents using polymers such as chitosan increases their efficacy, specificity and targeting ability. Green synthesis and characterization of metal nanoparticles such as silver with natural products extracted from some plants having antimicrobial properties, using the ecofriendly method one pot synthesis. Encapsulation of the new synthesized mixture using some biopolymers such as chitosan nanoparticles. The dispersions and homogeneity of the antimicrobial heterogeneous metal nanoparticles encapsulated by biopolymers will be characterized and confirmed by Fourier Transform Infrared Spectroscopy (FTIR), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM) and Zeta seizer. The effect of the antimicrobial biopolymer metal nano-formulations on normal human cell lines will be investigated to evaluate the environmental safety of these formulations. The antimicrobial toxic activity of the biopolymeric antimicrobial metal nanoparticles formulations will be will be investigated to evaluate their efficiency towards different pathogenic bacteria and fungi.

Keywords: antimicrobial, biodeterioration, chitosan, cultural heritage, silver

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794 Long-Term Otitis Media with Effusion and Related Hearing Loss and Its Impact on Developmental Outcomes

Authors: Aleema Rahman

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Introduction: This study aims to estimate the prevalence of long-term otitis media with effusion (OME) and hearing loss in a prospective longitudinal cohort studyand to study the relationship between the condition and educational and psychosocial outcomes. Methods: Analysis of data from the Avon Longitudinal Study of Parents and Children (ALSPAC) will be undertaken. ALSPAC is a longitudinal birth cohort study carried out in the UK, which has collected detailed measures of hearing on ~7000 children from the age of seven. A descriptive analysis of the data will be undertaken to estimate the prevalence of OME and hearing loss (defined as having average hearing levels > 20dB and type B tympanogram) at 7, 9, 11, and 15 years as well as that of long-term OME and hearing loss. Logistic and linear regression analyses will be conducted to examine associations between long-term OME and hearing loss and educational outcomes (grades obtained from standardised national attainment tests) and psychosocial outcomes such as anxiety, social fears, and depression at ages 10-11 and 15-16 years. Results: Results will be presented in terms of the prevalence of OME and hearing loss in the population at each age. The prevalence of long-term OME and hearing loss, defined as having OME and hearing loss at two or more time points, will also be reported. Furthermore, any associations between long-term OME and hearing loss and the educational and psychosocial outcomes will be presented. Analyses will take into account demographic factors such as sex and social deprivation and relevant confounders, including socioeconomic status, ethnicity, and IQ. Discussion: Findings from this study will provide new epidemiological information on the prevalence of long-term OME and hearing loss. The research will provide new knowledge on the impact of OME for the small group of children who do not grow out of condition by age 7 but continue to have hearing loss and need clinical care through later childhood. The study could have clinical implications and may influence service delivery for this group of children.

Keywords: educational attainment, hearing loss, otitis media with effusion, psychosocial development

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793 Design and Synthesis of Some Pyrimidine Derivatives as Bruton’s Tyrosine Kinase Inhibitors for Hematologic Malignancies

Authors: Ibrahim M. Labouta, Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Tamer M. Ibrahim, Nefertiti A. El-Nikhely

Abstract:

Bruton’s tyrosine kinase (BTK) is a critical effector molecule in B cell antigen receptor (BCR) signaling transduction. It regulates B cell proliferation, development and survival. Since BTK is widely expressed in many B cell leukaemias and lymphomas, targeting BTK by small molecules inhibitors became an attractive idea as new treatment modalities for B cell mediated hematologic malignancies. Ibrutinib is the 1st generation BTK inhibitor, approved by FDA for treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). It binds irreversibly to the unique cysteine (Cys481) within the ATP-binding pocket of BTK. Besides ibrutinib, many irreversible covalent BTK inhibitors comprising pyrimidine nucleus such as spebrutinib (phase IIb) showed high selectivity and potency when compared to it. In this study, the designed compounds were based on 5-cyano-2-methylsulfanyl pyrimidine core and decorated with electrophilic warheads which are essential for the optimal activity for targeted covalent inhibition (TCI). However, modifications at pyrimidine C4 or C6 were made by introduction of substituted amines which are provided to behave differently. The synthesized derivatives were evaluated for their anticancer activity in leukemia cell lines (e.g. THP-1). Results showed that, some derivatives exhibited antiproliferative activity with IC50 ranged from 5-50 μM, The in vitro enzymatic inhibitory assay for these compounds against BTK is still under investigation. Nevertheless, we could conclude from the initial biological screening that, the synthesized 4 or 6-subsitituted aminopyrimidines represent promising and novel antileukemic agents. Meanwhile, further studies are still needed to attribute this activity through targeting BTK enzyme and inhibition of BCR signaling pathway.

Keywords: BTK inhibitors, hematologic malignancies, structure based drug design (SBDD), targeted covalent inhibitors (TCI)

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792 Hematological Profiles of Visceral Leishmaniasis Patients before and after Treatment of Anti-Leishmanial Drugs at University of Gondar Leishmania Research and Treatment Center Northwest, Ethiopia

Authors: Fitsumbrhan Tajebe, Fadil Murad, Mitikie Tigabie, Mareye Abebaw, Tadele Alemu, Sefanit Abate, Rezika Mohammedw, Arega Yeshanew, Elias Shiferaw

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Background: Visceral leshimaniasis is a parasitic disease characterized by a systemic infection of phagocytic cells. Hematological parameters of these patients may be affected by the progress of the disease or treatment. Thus, the current study aimed to assess the hematological profiles of visceral leishmaniasis patients before and after treatment. Method: An institutional based retrospective cohort study was conducted among visceral leishmaniasis patients at University of Gondar Comprehensive Specialized Referral Hospital Leishmaniasis Research and Treatment Center from 2013 to 2018. Hematological profiles before initiation and after completion of treatment were extracted from registration book. Descriptive statics was presented using frequency and percentage. Paired t-test and Wilcoxon Signed rank test were used for comparing mean difference for normally and non- normally distributed data, respectively. Spearman and Pearson correlation analysis was used to describe the correlation of hematological parameters with different variables. P value < 0.05 was considered as statistically significant. Result: Except absolute nerutrophil count, post treatment hematological parameters show a significant increment compared to pretreatment one. The prevalence of anemia, leucopenia and thrombocytopenia was 85.5%, 83.4% and 75.8% prior to treatment and it was 58.3%, 38.2% and 19.2% after treatment, respectively. Moreover, parasite load of the disease showed statistically significant negative correlation with hematological profiles mainly with white blood cell and red blood cell. Conclusion: Majority of hematological profiles of patients with active VL have been restored after treatment, which might be associated with treatment effect on parasite proliferation and concentration of parasite in visceral organ, which directly affect hematological profiles.

Keywords: visceral leshimaniasis, hematological profile, anti-leshimanial drug, Gondar

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791 Formulation of the N-Acylethanolamine, Linoleoylethanolamide into Cubosomes for Delivery across the Blood-Brain Barrier

Authors: Younus Mohammad, Anita B. Fallah, Ben J. Boyd, Shakila B. Rizwan

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N-acylethanolamines (NAEs) are endogenous lipids, which have neuromodulatory properties. NAEs have shown neuroprotective properties in various neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and ischemic stroke. However, NAEs are eliminated rapidly in vivo by enzymatic hydrolysis. We propose to encapsulate NAEs in liquid crystalline nanoparticles (cubosomes) to increase their biological half-life and explore their therapeutic potential. Recently, we have reported the co-formulation and nanostructural characterization of cubosomes containing the NAE, oleoylethanolamide and a synthetic cubosome forming lipid phytantriol. Here, we report on the formulation of cubosomes with the NAE, linoleoylethanolamide (LEA) as the core cubosome forming lipid. LEA-cubosomes were formulated in the presence of three different steric stabilisers: two brain targeting ligands, Tween 80 and Pluronic P188 and a control, Pluronic F127. Size, morphology and internal structure of formulations were characterized by dynamic light scattering (DLS), cryogenic transmission electron microscopy (Cryo–TEM) and small angle X–ray scattering (SAXS), respectively. Chemical stability of LEA in formulations was investigated using high-performance liquid chromatography (HPLC). Cytotoxicity of formulations towards human cerebral microvascular endothelial cell line (hCMEC/D3) was also investigated using an MTT (3-[4, 5- dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay. All cubosome formulations had mean particle size of less than 250 nm and were uniformly distributed with polydispersity indices less than 0.2. Cubosomes produced had a bicontinuous cubic internal structure with an Im3m space group but different lattice parameters, indicating the different modes of interaction between the stabilisers and LEA. LEA in formulations was found to be chemically stable. At concentrations of up to 20 µg/mL LEA in the presence of all the stabilisers, greater than 80% cell viability was observed.

Keywords: blood-brain barrier, cubosomes, linoleoyl ethanolamide, N-acylethanolamines (NAEs)

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790 Hepatoprotective Assessment of L-Ascorbate 1-(2-Hydroxyethyl)-4,6-Dimethyl-1, 2-Dihydropyrimidine-2-on in Toxic Liver Damage Test

Authors: Vladimir Zobov, Nail Nazarov, Alexandra Vyshtakalyuk, Vyacheslav Semenov, Irina Galyametdinova, Vladimir Reznik

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The aim of this study was to investigate hepatoprotective properties of the Xymedon derivative L-ascorbate 1- (2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropyrimidine-2-one (XD), which exhibits high efficiency as actoprotector. The study was carried out on 68 male albino rats weighing 250-400 g using preventive exposure to the test preparation. Effectiveness of XD win comparison with effectiveness of Xymedon (original substance) after administration of the compounds in identical doses. Maximum dose was 20 mg/kg. The animals orally received Xymedon or its derivative in doses of 10 and 20 mg/kg over 4 days. In 1-1.5 h after drug administration, CCl4 in vegetable oil (1:1) in a dose of 2 ml/kg. Controls received CCl4 but without hepatoprotectors. Intact control group consisted of rats, not receiving CCl4 or other compounds. The next day after the last administration of CCl4 and compounds under study animals were dehematized under ether anesthesia, blood and liver samples were taken for biochemical and histological analysis. Xymedon and XD administered according to the preventice scheme, exerted hepatoprotective effects: Xymedon — in the dose of 20 mg/kg, XD — in doses of 10 and 20 mg/kg. The drugs under study had different effects on liver condition, affected by induction with CCl4. Xymedon had a more pronounced effect both on the ALT level, which can be elevated not only due to destructive changes in hepatocytes, but also as a cholestasis manifestation, and on the serum total protein level, which reflects protein synthesis in liver. XD had a more pronounced effect on AST level, which is one of the markers of hepatocyte damage. Lower effective dose of XD — 10 mg/kg, compared to Xymedon effective according to, and its pronounced effect on AST, the hepatocyte cytolysis marker, is indicative of its higher preventive effectiveness, compared to Xymedon. This work was performed with the financial support of Russian Science Foundation (grant No: 14-50-00014).

Keywords: hepatoprotectors, pyrimidine derivatives, toxic liver damage, xymedon

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789 Scenario Analysis to Assess the Competitiveness of Hydrogen in Securing the Italian Energy System

Authors: Gianvito Colucci, Valeria Di Cosmo, Matteo Nicoli, Orsola Maria Robasto, Laura Savoldi

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The hydrogen value chain deployment is likely to be boosted in the near term by the energy security measures planned by European countries to face the recent energy crisis. In this context, some countries are recognized to have a crucial role in the geopolitics of hydrogen as importers, consumers and exporters. According to the European Hydrogen Backbone Initiative, Italy would be part of one of the 5 corridors that will shape the European hydrogen market. However, the set targets are very ambitious and require large investments to rapidly develop effective hydrogen policies: in this regard, scenario analysis is becoming increasingly important to support energy planning, and energy system optimization models appear to be suitable tools to quantitively carry on that kind of analysis. The work aims to assess the competitiveness of hydrogen in contributing to the Italian energy security in the coming years, under different price and import conditions, using the energy system model TEMOA-Italy. A wide spectrum of hydrogen technologies is included in the analysis, covering the production, storage, delivery, and end-uses stages. National production from fossil fuels with and without CCS, as well as electrolysis and import of low-carbon hydrogen from North Africa, are the supply solutions that would compete with other ones, such as natural gas, biomethane and electricity value chains, to satisfy sectoral energy needs (transport, industry, buildings, agriculture). Scenario analysis is then used to study the competition under different price and import conditions. The use of TEMOA-Italy allows the work to catch the interaction between the economy and technological detail, which is much needed in the energy policies assessment, while the transparency of the analysis and of the results is ensured by the full accessibility of the TEMOA open-source modeling framework.

Keywords: energy security, energy system optimization models, hydrogen, natural gas, open-source modeling, scenario analysis, TEMOA

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788 Migrants’ English Language Proficiency and Health care Access; A Qualitative Study in South Wales United Kingdom

Authors: Qirat Naz

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The aim of this research study is to explore the perspectives of migrants and interpreters from diverse backgrounds on language barriers, their English language proficiency and access to health care facilities. A qualitative research methodology was used including in-depth interviews and focus group discussions. Data was collected from 20 migrants who have difficulty conversing in the English language and 12 interpreters including family members and friends who provide translation services as part of accessing health care. The findings seek to address three key research questions: how language is a barrier for non-national language speakers to access the health care facilities, what is the impact of various socio-cultural and linguistic backgrounds on health compliance, and what is the role of interpreters in providing access to, usage of, and satisfaction with health-care facilities. The most crucial component of providing care was found to be effective communication between patient and health care professionals. Language barrier was the major concern for healthcare professionals in providing and for migrants in accessing sufficient, suitable, and productive health care facilities. Language and sociocultural background play a significant role in health compliance as this research reported; respondents believe that patients who interact with the doctors who have same sociocultural and linguistic background benefit from receiving better medical care than those who do not. Language limitations and the socio-cultural gap make it difficult for patients and medical staff to communicate clearly with one another, which has a negative effect on quality of care and patient satisfaction. The use of qualified interpreters was found to be beneficial but there were also drawbacks such as accessibility and availability of them in a timely manner for patient needs. The findings of this research can help health care workers and policy makers working to improve health care delivery system and to create appropriate strategies to overcome this challenge.

Keywords: migration, migrants, language barrier, healthcare access

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787 Development and Characterization of Multiphase Hydrogel Systems for Wound Healing

Authors: Rajendra Jangde, Deependra Singh

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Present work was based with objective to release of the antimicrobial and debriding agent in sustained manner at the wound surface. In order to provide a long-lasting antimicrobial action and moist environment on wound space, Biocompatible moist system was developed for complete healing. In the present study, a biocompatible moist system of PVA-gelatin hydrogel was developed capable of carrying multiple drugs- Quercetin and Cabopol in controlled manner for effective and complete wound healing. Carbopol and Quercetin were prepared by thin film hydration techniques and optimized system was incorporated in PVA-Gelatin slurry. PVA-Gelatin hydrogels were prepared by freeze thaw method. The prepared dispersion was casted into films to prepare multiphase hydrogel system and characterized by in vitro and in vivo studies. Results revealed the uniform dispersion of microspheres in a three-dimensional matrix of the PVA-Gelatin hydrogel observed at different magnifications. The in vitro release data showed typical biphasic release pattern, i.e., a burst release followed by a slower sustained release for 5 days. Prepared system was found to be stable under both normal and accelerated conditions. Histopathological study showed significant (p<0.05) increase in fibroblast cells, collagen fibres and blood vessels formation. All parameters such as wound contraction, tensile strength, histopathological and biochemical parameters- hydroxyproline content, protein level, etc. were observed significant (p<0.05) in comparison to control group. Present results suggest an accelerated re-epithelialization under moist wound environment with delivery of multiple drugs effective at different stages of wound healing cascade with minimum disturbance of wound bed.

Keywords: multiphase hydrogel, optimization quercetin, wound healing

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786 Bioinformatics Identification of Rare Codon Clusters in Proteins Structure of HBV

Authors: Abdorrasoul Malekpour, Mohammad Ghorbani Mojtaba Mortazavi, Mohammadreza Fattahi, Mohammad Hassan Meshkibaf, Ali Fakhrzad, Saeid Salehi, Saeideh Zahedi, Amir Ahmadimoghaddam, Parviz Farzadnia Dr., Mohammadreza Hajyani Asl Bs

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Hepatitis B as an infectious disease has eight main genotypes (A–H). The aim of this study is to Bioinformatically identify Rare Codon Clusters (RCC) in proteins structure of HBV. For detection of protein family accession numbers (Pfam) of HBV proteins; used of uni-prot database and Pfam search tool were used. Obtained Pfam IDs were analyzed in Sherlocc program and RCCs in HBV proteins were detected. In further, the structures of TrEMBL entries proteins studied in PDB database and 3D structures of the HBV proteins and locations of RCCs were visualized and studied using Swiss PDB Viewer software. Pfam search tool have found nine significant hits and 0 insignificant hits in 3 frames. Results of Pfams studied in the Sherlocc program show this program not identified RCCs in the external core antigen (PF08290) and truncated HBeAg protein (PF08290). By contrast the RCCs become identified in Hepatitis core antigen (PF00906) Large envelope protein S (PF00695), X protein (PF00739), DNA polymerase (viral) N-terminal domain (PF00242) and Protein P (Pf00336). In HBV genome, seven RCC identified that found in hepatitis core antigen, large envelope protein S and DNA polymerase proteins and proteins structures of TrEMBL entries sequences that reported in Sherlocc program outputs are not complete. Based on situation of RCC in structure of HBV proteins, it suggested those RCCs are important in HBV life cycle. We hoped that this study provide a new and deep perspective in protein research and drug design for treatment of HBV.

Keywords: rare codon clusters, hepatitis B virus, bioinformatic study, infectious disease

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785 Alcohol Septal Ablation in a 19-Year-Old with Hypertrophic Obstructive Cardiomyopathy Patient: A Case Report

Authors: Christine Ysabelle G. Roman, Pauline Torres

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Background: Hypertrophic cardiomyopathy is a disease of marked heterogeneity. It is a genetically determined heart disease characterized by significant myocardium hypertrophy that results in diastolic dysfunction, left ventricular outflow tract obstruction, and an increased risk of arrhythmias. The primary treatment in patients with such conditions is negative inotropic drugs, such as beta-blockers, calcium channel antagonists, and disopyramide. However, for those who remain symptomatic and need septal reduction therapy, surgical septal myectomy or alcohol septal ablation are options. Case Summary: A 19 – year old female presented in the authors’ institution with easy fatigability. The consult was done a year prior, and 2D echocardiography was requested which showed concentric left ventricular hypertrophy, asymmetrically hypertrophied interventricular septum (IVS) with the largest diameter of 3.3cm & subaortic dynamic obstruction with a maximum gradient of 47 mmHg. A repeat echo a year later showed asymmetric septal hypertrophy (IVS measuring at 3cm) with the systolic anterior motion of anterior mitral valve leaflet and left ventricular outflow tract obstruction (peak gradient of 50mmHg). The patient then underwent alcohol septal ablation and was discharged stable after four days of admission. Conclusion: Hypertrophic obstructive cardiomyopathy, a cardiovascular genetic disease, results in various patterns of left ventricular hypertrophy and abnormality of mitral valve apparatus. The patient is managed medically initially. However, despite optimal drug therapy and significant left ventricular outflow tract obstruction, significant heart failure symptoms or syncope require invasive treatment.

Keywords: hypertrophic obstructive cardiomyopathy, left ventricular outflow tract obstruction, alcohol septal ablation, alcohol

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784 Antibacterial Activities of Lactic Acid Bacteria on Potential Multidrug - Resistant Pathogens Isolated from Rabbit

Authors: Checkfaith I. Aizebeoje, Temitope O. Lawal, Bolanle A. Adeniyi

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The overuse and abuse of antibiotics in treating zoonotic infections in humans and opportunistic infections in rabbit has contributed to the increase in antimicrobial drug resistance, therefore, an alternative to antibiotics is needed in treating these infections. The study was carried out to determine the antimicrobial activity of lactic acid bacteria (LAB) isolated from rabbit’s faeces against multidrug-resistant (MDR) pathogens isolated from the same rabbit. Twelve faecal samples and twelve swabs from fur samples were randomly collected aseptically from apparently healthy rabbits from Ajibode, Ibadan and University of Ibadan research farm in Ibadan, Oyo state, Nigeria. Lactic acid bacteria and multidrug-resistant pathogens were isolated using appropriate agar media and identified by partial sequencing of the 16SrRNA gene. Antibiotic susceptibility pattern of isolated bacteria and LAB were determined by the agar diffusion method. The antibacterial activity of the LAB against the test pathogens was determined using the agar overlay and agar diffusion methods. The pathogens Myroides gitamensis, Citrobacter rodentium, Acinetobacter johnsonii, Enterobacter oryzendophyticus and Serratia marcescens as well as twenty-eight (28) species of LAB belonging to Acetobacter and Lactobacillus genera were identified and characterized. Lactobacillus plantarum had the highest (60.71%) occurrence of the LAB. Viable cells and cell free supernatant (CFS) of isolated LAB inhibited the growth of the test organisms with the largest zone of inhibition (40 mm) produced by Lactobacillus plantarum against Citrobacter rodentium. This study showed that LAB from rabbit possess considerable antibacterial activity against multidrug-resistant bacteria from the same environment.

Keywords: antibacterial activities, cell-free supernatant, lactic acid bacteria; multidrug-resistant pathogens, rabbits’ faeces

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783 Carbon-Based Electrochemical Detection of Pharmaceuticals from Water

Authors: M. Ardelean, F. Manea, A. Pop, J. Schoonman

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The presence of pharmaceuticals in the environment and especially in water has gained increasing attention. They are included in emerging class of pollutants, and for most of them, legal limits have not been set-up due to their impact on human health and ecosystem was not determined and/or there is not the advanced analytical method for their quantification. In this context, the development of various advanced analytical methods for the quantification of pharmaceuticals in water is required. The electrochemical methods are known to exhibit the great potential for high-performance analytical methods but their performance is in direct relation to the electrode material and the operating techniques. In this study, two types of carbon-based electrodes materials, i.e., boron-doped diamond (BDD) and carbon nanofiber (CNF)-epoxy composite electrodes have been investigated through voltammetric techniques for the detection of naproxen in water. The comparative electrochemical behavior of naproxen (NPX) on both BDD and CNF electrodes was studied by cyclic voltammetry, and the well-defined peak corresponding to NPX oxidation was found for each electrode. NPX oxidation occurred on BDD electrode at the potential value of about +1.4 V/SCE (saturated calomel electrode) and at about +1.2 V/SCE for CNF electrode. The sensitivities for NPX detection were similar for both carbon-based electrode and thus, CNF electrode exhibited superiority in relation to the detection potential. Differential-pulsed voltammetry (DPV) and square-wave voltammetry (SWV) techniques were exploited to improve the electroanalytical performance for the NPX detection, and the best results related to the sensitivity of 9.959 µA·µM-1 were achieved using DPV. In addition, the simultaneous detection of NPX and fluoxetine -a very common antidepressive drug, also present in water, was studied using CNF electrode and very good results were obtained. The detection potential values that allowed a good separation of the detection signals together with the good sensitivities were appropriate for the simultaneous detection of both tested pharmaceuticals. These results reclaim CNF electrode as a valuable tool for the individual/simultaneous detection of pharmaceuticals in water.

Keywords: boron-doped diamond electrode, carbon nanofiber-epoxy composite electrode, emerging pollutans, pharmaceuticals

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782 Community Involvement in Reducing Maternal and Perinatal Mortality in Cross River State, Nigeria: 'The Saving Mother Giving Life' Strategic Approach in Cross River State

Authors: Oluwayemisi Femi-Pius, Kazeem Arogundade, Eberechukwu Eke, Jimmy Eko

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Introduction: Globally, community involvement in improving their own health has been widely adopted as a strategy in Sub-Saharan Africa principally to ensure equitable access to essential health care as well as improve the uptake of maternal and newborn health services especially in poor-resource settings. Method: The Saving Mother Giving Life (SMGL) Initiative implemented by Pathfinder International with funding support from USAID conducted a Health Facility Assessment (HFA) and found out that maternal mortality ratio in Cross River State was 812 per 100,000 live birth and perinatal mortality was 160 per 1000 live birth. To reduce maternal and perinatal mortality, Pathfinder International mobilized, selected and trained community members as community volunteers, traditional birth attendants, and emergency transport service volunteer drivers mainly to address the delay in decision making and reaching the health facility among pregnant women. Results: The results showed that maternal mortality ratio in Cross River State decrease by 25% from 812 per 100,000 live birth at baseline to 206 per 100,000 live birth at June 2018 and perinatal mortality reduced by 35% from 160 per 100,000 at baseline to 58 per 1000 live birth at June 2018. Data also show that ANC visit increased from 7,451 to 11,344; institutional delivery increased from 8,931 at baseline to 10,784 in June 2018. There was also a remarkable uptake of post-partum family planning from 0 at baseline to 233 in June 2018. Conclusion: There is clear evidence that community involvement yields positive maternal outcomes and is pivotal for sustaining most health interventions.

Keywords: maternal mortality, Nigeria, pathfinder international, perinatal mortality, saving mother giving life

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781 Tibial Hemimelia Type VIIa: A Case Report

Authors: M. Medrano, M. D. M. S., L. Younes, M. D.

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Introduction: Incidence of tibial hemimelia is 1:1,000,000. Due to pre-existing case studies and literature, there is now a better understanding of the genetics, etiology and pathoanatomy of tibial hemimelia, but an underlying cause is generally unknown. This presentation aims to discuss a rare, congenital lower limb deficiency observed in a patient in order to identify potential prenatal risk factors and future considerations for the patient’s well-being. Observation: A newborn female child, born full term via spontaneous vaginal delivery after induction of labor to unaffected and non-consanguineous parents. The prenatal course was notable for limited and disjointed prenatal care as well as maternal tobacco and marijuana use, anemia of pregnancy, and inadequate weight gain. Prenatal imaging showed lower extremity deformity with the inability to visualize tibia and bilateral clubfeet in the setting of Intrauterine Growth Restriction (IUGR). The patient presented with right equino varus deformity of the foot and right knee joint deformity. Radiological imaging showed the absence of the right tibia and varus angulation of the right foot with dislocation of the tibiotalar joint. Normal femur with lateral and mild anterior displacement of a wide fibula (Weber Type VIIa). Due to the absence of the patient’s tibia and knee extensor mechanism, the patient was not a candidate for reconstructive surgery and ultimately underwent successful right knee disarticulation. Discussion and Conclusion: By utilizing a retrospective chart review of this case, possible risk factors in prenatal care may be identified and add to existing knowledge on etiology. Hopefully, a cause can be clearly identified in the future and, thus, addressed in the prenatal period. In addition, we can investigate the patient’s well-being and adjustment post-operatively to support outpatient management of an uncommon anomaly.

Keywords: Tibial hemimelia, prenatal care, pediatric orthopedics, congenital deformity

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780 Genetic Variation in CYP4F2 and VKORC1: Pharmacogenomics Implications for Response to Warfarin

Authors: Zinhle Cindi, Collet Dandara, Mpiko Ntsekhe, Edson Makambwa, Miguel Larceda

Abstract:

Background: Warfarin is the most commonly used drug in the management of thromboembolic disease. However, there is a huge variability in the time, number of doses or starting doses for patients to achieve the required international normalised ratio (INR) which is compounded by a narrow therapeutic index. Many genetic-association studies have reported on European and Asian populations which have led to the designing of specific algorithms that are now being used to assist in warfarin dosing. However, very few or no studies have looked at the pharmacogenetics of warfarin in African populations, yet, huge differences in dosage requirements to reach the same INR have been observed. Objective: We set out to investigate the distribution of 3 SNPs CYP4F2 c.1347C > T, VKORC1 g.-1639G > A and VKORC1 c.1173C > T among South African Mixed Ancestry (MA) and Black African patients. Methods: DNA was extracted from 383 participants and subsequently genotyped using PCR/RFLP for the CYP4F2 c.1347 (V433M) (rs2108622), VKORC1 g.-1639 (rs9923231) and VKORC1 c.1173 (rs9934438) SNPs. Results: Comparing the Black and MA groups, significant differences were observed in the distribution of the following genotypes; CYP4F2 c.1347C/T (23% vs. 39% p=0.03). All VKORC1 g.-1639G > A genotypes (p < 0.006) and all VKORC1 c.1173C > T genotypes (p < 0.007). Conclusion: CYP4F2 c.1347T (V433M) reduces CYP4F2 protein levels and therefore expected to affect the amount of warfarin needed to block vitamin k recycling. The VKORC1 g-1639A variant alters transcriptional regulation therefore affecting the function of vitamin k epoxide reductase in vitamin k production. The VKORC1 c.1173T variant reduces the enzyme activity of VKORC1 consequently enhancing the effectiveness of warfarin. These are preliminary results; more genetic characterization is required to understand all the genetic determinants affecting how patients respond to warfarin.

Keywords: algorithms, pharmacogenetics, thromboembolic disease, warfarin

Procedia PDF Downloads 232
779 A Randomised Controlled Trial on the Nurse-Led Smartphone-Based Self-Management Programme for Type 2 Diabetes Patients with Poor Glycemic Control

Authors: Wenru Wang

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Over the past decades, Asia has emerged as the ‘diabetes epicentre’ in the world due to rapid economic development, urbanization and nutrition transition. There is an urgent need to develop more effective and cost-effective care management strategies in response to this rising diabetes epidemic. This study aims to develop and compare a nurse-led smartphone-based self-management programme with an existing nurse-led diabetes service on health-related outcomes among type 2 diabetes patients with poor glycemic control in Singapore. We proposed a randomized controlled trial with pre- and repeated post-tests control group design. A total of 128 type 2 diabetes patients with poor glycemic control will be recruited from the diabetes clinic of an acute public hospital in Singapore through convenience sampling. Study participants will be either randomly allocated to the experimental group or control group. Outcome measures used will include the 10-item General Self-Efficacy Scale, 11-item Revised Summary of Diabetes Self-care Activities, and 19-item Diabetes-Dependent Quality of Life. Data will be collected at 3-time points: baseline, three months and six months from the baseline, respectively. It is expected that this programme will be an alternative offered to diabetes patients to master their self-care management skills, in addition to the existing diabetes service provided in diabetes clinics in Singapore hospitals. Also, the self-supporting and less resource-intensive nature of this programme, through the use of smartphone app as a mode of intervention delivery, will greatly reduce nurses’ direct contact time with patients and allow more time to be allocated to those who require more attention. The study has been registered with clinicaltrials.gov. The trial registration number is NCT03088475.

Keywords: type 2 diabetes, poor glycaemic control, nurse-led, smartphone-based, self-management, health-relevant outcomes

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778 A New Technology for Metformin Hydrochloride Mucoadhesive Microparticles Preparation Utilizing BÜCHI Nano-Spray Dryer B-90

Authors: Tamer M. Shehata

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Objective: Currently, mucoadhesive microparticles acquired a high interest in both research and pharmaceutical technology fields. Recently, BÜCHI lunched its latest fourth generation nano spray dryer B-90 used for nanoparticle production. B-90 offers an elegant technology combined particle engineering and drying in one step. In our laboratory, we successfully developed a new formulation for metformin hydrochloride, mucoadhesive microparticles utilizing B-90 technology for treatment of type 2-diabetis. Method: Gelatin or sodium alginate, natural occurring polymers with mucoadhesive properties, solely or in combination was used in our formulation trials. Preformulation studies (atomization head mesh size, flow rate, head temperature, polymer solution viscosity and surface tension) and postformulation characters (particle size, flowability, surface scan and dissolution profile) were evaluated. Finally, hypoglycemic effect of the selected formula was evaluated in streptozotocin-induced diabetic rats. Spray head with 7 µm hole, flow rate of 3.5 mL/min and head temperature 120 ºC were selected. Polymer viscosity was less than 11.5 cP with surface tension less than 70.1 dyne/cm. Result: Discrete, non aggregated particles and free flowing powders with particle size was less than 2000 nm were obtained. Gelatin and sodium alginate combination in ratio 1:3 were successfully sustained the in vitro release profile of the drug. Hypoglycemic evaluation of the previous formula, showed a significant reduction of blood glucose level over 24 h. Conclusion: B-90 technology can open a new era of , mucoadhesive microparticles preparation offering convenient dosage form that can enhance compliance of type 2 diabetic patients.

Keywords: mucoadhesive, microparticles, technology, diabetis

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777 [Keynote Talk]: Treatment Satisfaction and Safety of Sitagliptin versus Pioglitazone in Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Metformin Monotherapy

Authors: Shahnaz Haque, Anand Shukla, Sunita Singh, Anil Kem

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Introduction: Diabetes Mellitus is a chronic metabolic disease affecting millions worldwide. Metformin is the most commonly prescribed first line oral hypoglycemic drug for type 2 diabetes mellitus, but due to progressive worsening of blood glucose control during the natural history of type 2 diabetes, combination therapy usually becomes necessary. Objective: This study was designed to assess the treatment satisfaction between Sitagliptin versus Pioglitazone added to Metformin in patients with type 2 diabetes mellitus (T2DM). Methods: We conducted a prospective, open label, randomized, parallel group study in SIMS, Hapur, U.P. Eligible patients fulfilling inclusion criteria were randomized into two groups having 25 patients in each group using tab Sitagliptin 100mg, tab Pioglitazone 30mg added to ongoing tab Metformin (500mg) therapy for 16 weeks. The follow-up visits were on weeks 4,12 and 16. Result: 16 weeks later, addition of Sitagliptin 100mg compared to that of Pioglitazone 30 mg to ongoing Metformin therapy provided similar glycosylated hemoglobin (HbA1c) lowering efficacy in patients with T2DM with inadequate glycemic control on metformin monotherapy. Change in HbA1c in group1 was -0.656±0.21%(p<0.0001) whereas in group2 was -0.748±0.35%(p<0.0001). Hence decrease in HbA1c from baseline was more in group2. Both treatments were well tolerated with negligible risk of hypoglycaemia. Weight loss was observed with Sitagliptin in contrast to weight gain seen in Pioglitazone. Conclusion: In this study, Sitagliptin 100 mg along with metformin therapy in comparison to pioglitazone 30 mg plus metformin therapy was both effective, well-tolerated and improved glycemic control in both the groups. Addition of pioglitazone had cause oedema and weight gain to the patients whereas sitagliptin caused weight loss in its patients.

Keywords: sitagliptin, pioglitazone, metformin, type 2 diabetes mellitus

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776 Silica Nanoparticles Induced Oxidative Stress and Inflammation in MRC-5 Human Lung Fibroblasts

Authors: Anca Dinischiotu, Sorina Nicoleta Voicu

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Silica nanoparticles (SiO2-NPs) are widely used in consumer products such as paints, plastics, insulation materials, tires, concrete production, as well as in gene delivery systems and imaging procedures. Environmental human exposure to them occurs during utilization of these products, in a time-dependent manner, the uptake being by topic and inhalation route especially. SiO2-NPs enter cells and induce membrane damage, oxidative stress and inflammatory reactions in a concentration-dependent manner. In this study, MRC-5 cells (human fetal lung fibroblasts) were exposed to amorphous SiO2-NPs at a dose of 62.5 μg/ml for 24, 48 and 72 hours. The size distribution of NPs was a lognormal function, in the range 3-14 nm. A time-dependent decrease of total reduced glutathione concentration by 36%, 50%, and 78% and an increase of NO level by 62%, 32%, respectively 24% compared to control were noticed. An up-regulation of NF-kB expression by 20%, 50% respectively 10% and of Nrf-2 by 139%, 58%, and 16% compared to control after 24, 48 and 72 hours was noticed also. The expression of IL-1β, IL-6, IL-8, and COX-2 was up-regulated in a time-dependent manner. Also, the expression of MMP-2 and MMP-9 were down-regulated after 48 and 72 hours, whereas their activities raised in a time-dependent manner. Exposure of cells to NPs up-regulated the expression of inducible NO synthase, as previously was shown, and probably this is the reason for the increased level of NO, that can react with the thiol groups of reduced glutathione molecules, diminishing its concentration Nrf2 is a transcription factor translocated in nucleus, under oxidative stress, where downstream gene expression activates in order to modulate the adaptive intracellular response against oxidative stress. The cross-talk between Nrf2 and NF-kB activities regulates the inflammatory processes. The activation of NF-kB could activate up-regulation of IL-1β, IL-6, and IL-8. The increase of COX-2 expression could be correlated with IL-1β one. Also, probably in response to the pro-inflammatory cytokines, MMP-2 and MMP-9 were induced and activated. In conclusion, the exposure of MRC-5 cells to SiO2-NPs generated inflammation in a time-dependent manner.

Keywords: inflammation, MRC-5 cells, oxidative stress, silica nanoparticles

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775 Human Capital Development: A Pivotal for Sustainable Development in Developing Countries

Authors: Yusuf Ismaila

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The developing countries are characterized by inefficient production systems and unequal distribution of wealth. Developing countries are largely populated, yet under developed. This can be attributed partly to the unplanned efforts towards the development of human capital through education and training. In the developed nations a huge attention is accorded to indices such as life expectancy, literacy, infant mortality, education, and the efficient delivery of social services. This is the reason why many developing countries have been scored low by the United Nations in terms of its human development indicators. The population growth continued to expand far beyond the rate of economic growth, a situation that gave rise to increasing poverty. This paper examines the effect of selected human development indicators on the economic development. Thus human capital development is one of the fundamental solutions to enter the international arena. Both quantitative and qualitative analyses were used to demonstrate the effect of selected human capital indices and related literatures were also reviewed for exposition of the human capital concept. It was found that there are no conscious efforts in human capital planning. This has therefore resulted to continuing dwindling of production system and poverty. Recommendations made to redress the situation include that human capital development should be planned and adequately funded in line with the needs of the economy and by applying international standards. Specifically, developing countries must invest necessary resources in developing human capital which tend to have a great impact on sustainable development. Information about the labour market should improve while government policy should favour labour mobility. HCD strategy must focus on improving the skills of the workforce, reducing the cost of doing business and making available the resources business needs to compete and thrive in a fast globalizing economy. There should be regular interaction of planners, employers and builders of human capital to facilitate the process of meaningful national development.

Keywords: economic development, human capital, economic growth, developing countries

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774 Gendered Economic, Social, and Health Effects of the Mobile Health and Nutritional Services of the International Medical Corps (IMC) in Vulnerable Areas of Ethiopia

Authors: Abdela Zeinu Yasin

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The current research aimed to assess the status of IMC in providing treatment for malnourished children and programs in water, sanitation, and hygiene (WASH), food and livelihood security, and comprehensive healthcare through Mobile health and nutrition programs during the last 5 years period. We have conducted 60 in-depth interviews with women during the period from conception to a child’s birthday, health facility staff, and female community health volunteers (FCHVs), as well as 12 focus group discussions with health facility staff and other household decision-makers. We employed thematic analysis using framework matrices and analytical memorandums. The study revealed that 78% of the respondents, of whom 97% were women, have benefited from the selected vulnerable areas. The use of the clear water and sanitization program has reached the 81% of selected households. The use of a modern baby delivery system among the respondent has been 68% of the women and health facilities among the decision-makers/focal person. More than 8 in 10 participants (84%) could read and understand the health facility instructions, and the majority (82%) of women, health facility staff, and male decision-makers can also read and write bulletins and instructions. We found that decision-maker women preferred participative education, whereas health facilities and the IMC desired educational and motivational bulletins. A Mobile Health and Nutrition program intervention by the IMC is acceptable in the conditions of the Ethiopian community and has the potential to improve community health and nutrition service utilization, particularly by providing clean water and sanitization; women’s birth control, and health improvement in the vulnerable regions of the country. The current research findings shall contribute to text IMC Mobile Health and Nutritional intervention design in under-resourced settings.

Keywords: clean water, health and nutrition services, hygiene, IMC, mobile health, sanitation

Procedia PDF Downloads 63
773 Effect of Yeast Selenium on CD4 T Cell and WAZ of HIV1 Positive Children in Nyamasaria in Kisumu Kenya

Authors: S. B. Otieno1, F. Were, A. Afullo, K. Waza

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Background: Multi drug resistance HIV has emerged rendering the current conventional treatment of HIV ineffective. There is a need for new treatment regime which is cheap, effective and not prone to resistance development by HIV. Methods: In randomized clinical study of 68 HIV positive children 3 – 15 years to asses the efficacy of yeast selenium in HIV/AIDS patients, 50μ yeast selenium was administered to 34 children while in matched control of 34 were put on placebo. Blood samples and weight of the both groups which were taken every 3 months intervals up to 6 months, were analyzed by ELIZA for CD4T cells, the data was analyzed by SPSS version 16, WAZ scores were analyzed by Epi Info version 6. Results: No significant difference in age { χ2 (1, 62) =0.03, p =0.853}, cause of morbidity between test and controls {χ2 (1, 65) = 5.87, p= 0.015} and on condition of foster parents {χ2 ( 1,63) = 5.57, p= 0.0172} was observed. Children on selenium showed progressive improvement of WAZ and significant difference at six months {F (5,12) = =5.758, P=0.006}, and weight gain of up to 4.1 kilograms in six months, and significant CD4 T cell count increase t= -2.943, p<0.05 compared to matched controls t = -1.258 p> 0.05. CD4 T cell count increased among all age groups on test 3-5 years (+ 267.1),5-8 years (+200.3) 9-15 years (+71.2) cells/mm3 and in matched controls a decrease 3-5 years (-71), 5-8 years (-125) and 9-13 years (-10.1) cells/mm3 . No significant difference inCD4 T cell count between boys {F (2, 32) = 1.531 p= 0.232} and between boys {F (2, 49) = 1.040, p= 0.361} on test and between boys and girls {F (5, 81) = 1.379, p= 0.241} on test. Similarly no significant difference between boys and girls were observed {F (5, 86) = 1.168, p= 0.332}.In the test group there was significant positive correlation β =252.23 between weight for age (WAZ), and CD4 T Cell Count p=0.007, R2= 0.252, F< 0.05. In matched controls no significant correlation between weight gain and CD4 T cell count change was observed at six months p > 0.05. No positive correlation β =-138.23 was observed between CD4T Cell count, WAZ, p=0.934, R2 =0.0337 F >0.05. Majority (96.78%) of children on test either remained or progressed to WHO immunological stage I. Conclusion: From this study it can be concluded that yeast Selenium is effective in slowing the progress of HIV 1 in children from WHO clinical stage I by improving CD4 T cell count and hence the immunity.

Keywords: selenium, HIV, AIDS, WAZ

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772 Challenges in the Management of Her2 Neu Positive Breast Cancer Patients: Real World Data from India

Authors: Praveen Adusumilli, Meher Lakshmi Konatam, Sadashivudu Gundeti, Stalin Bala

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The invention of trastuzumab has changed the treatment of breast cancer and lives of many patients all over the world. Despite many patients getting benefitted from the drug, it is out of reach for most of the patients. There is very limited real world data regarding the epidemiology and clinical outcome of Her2neu positive breast cancer patients. Materials and Methods: This is a retrospective analysis of breast cancer patients presenting to a tertiary care cancer centre in Southern India from 2007 to2013. All early and locally advanced breast cancer patients, who were Her2neu 3+ on IHC are included in the study and evaluated in terms of epidemiology, 3-year disease free survival (DFS)and 5-year overall survival(OS). Chemotherapy regimens used were-FAC 6 cycles or AC 4 cycles followed by 12 cycles of weekly paclitaxel . Trastuzumab was given after 6 cycles of FAC or weekly with paclitaxel followed by 3weekly maintenance until 1 year. Results: Over the period of this study there were 885 newly diagnosed cases of carcinoma breast, of which 242 (27%) were Her2neu positive, 360(40%) were hormone receptor positive, and 212(24%) were triple negative. A total of 71(8%) were Her2neu equivocal of which only 10 patients got FISH test done. Of the 212 newly diagnosed patients, only 74 (29%) opted to have standard of care therapy with trastuzumab at our centre, out of which 52(24%), 8(3%), received under insurance, paying basis respectively. 14(9%) patients received the care as part of clinical trial program (ALTTO trial). 7 (9.72%) patients developed decrease of ejection fraction by greater than 10%, requiring stoppage of trastuzumab out of which 5 were restarted in 2 months. Patients receiving trastuzumab along with chemotherapy had longer 3year DFS 92% vs. 60% (p value<0.0001) when compared to chemotherapy alone. 5 year OS was 87% vs 44% (p-value <0.0001) compared to chemotherapy alone. Conclusion: Trastuzumab with chemotherapy improves the DFS and OS in Her2neu positive patients. The biggest constraint is the cost of the treatment and absence of universal health security net to treat all patients with this diagnosis.

Keywords: breast cancer, Her 2 neu positive, real world data, Trastuzumab

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771 Identification of the Key Enzyme of Roseoflavin Biosynthesis

Authors: V. Konjik, J. Schwartz, R. Sandhoff, M. Mack

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The rising number of multi-resistant pathogens demands the development of new antibiotics in order to reduce the lethal risk of infections. Here, we investigate roseoflavin, a vitamin B2 analogue which is produced by Streptomyces davawensis and Streptomyces cinnabarinus. We consider roseoflavin to be a 'Trojan horse' compound. Its chemical structure is very similar to riboflavin but in fact it is a toxin. Furthermore, it is a clever strategy with regard to the delivery of an antibiotic to its site of action but also with regard to the production of this chemical: The producer cell has only to convert a vitamin (which is already present in the cytoplasm) into a vitamin analog. Roseoflavin inhibits the activity of Flavin depending proteins, which makes up to 3.5 % of predicted proteins in organisms sequenced so far. We sequentially knocked out gene clusters and later on single genes in order to find the ones which are involved in the roseoflavin biosynthesis. Consequently, we identified the gene rosB, coding for the protein carrying out the first step of roseoflavin biosynthesis, starting form Flavin mononucleotide. Here we show, that the protein RosB has so far unknown features. It is per se an oxidoreductase, a decarboxylase and an aminotransferase, all rolled into one enzyme. A screen of cofactors revealed needs of oxygen, NAD+, thiamine and glutamic acid to carry out its function. Surprisingly, thiamine is not only needed for the decaboxylation step, but also for the oxidation of 8-demethyl-8-formyl Flavin mononucleotide. We had managed to isolate three different Flavin intermediates with different oxidation states, which gave us a mechanistic insight of RosB functionality. Our work points to a so far new function of thiamine in Streptomyces davawensis. Additionally, RosB could be extremely useful for chemical synthesis. Careful engineering of RosB may allow the site-specific replacement of methyl groups by amino groups in polyaromatic compounds of commercial interest. Finally, the complete clarification of the roseoflavin biosynthesis opens the possibility of engineering cost-effective roseoflavin producing strains.

Keywords: antibiotic, flavin analogue, roseoflavin biosynthesis, vitamin B2

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770 Evaluation of Golden Beam Data for the Commissioning of 6 and 18 MV Photons Beams in Varian Linear Accelerator

Authors: Shoukat Ali, Abdul Qadir Jandga, Amjad Hussain

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Objective: The main purpose of this study is to compare the Percent Depth dose (PDD) and In-plane and cross-plane profiles of Varian Golden beam data to the measured data of 6 and 18 MV photons for the commissioning of Eclipse treatment planning system. Introduction: Commissioning of treatment planning system requires an extensive acquisition of beam data for the clinical use of linear accelerators. Accurate dose delivery require to enter the PDDs, Profiles and dose rate tables for open and wedges fields into treatment planning system, enabling to calculate the MUs and dose distribution. Varian offers a generic set of beam data as a reference data, however not recommend for clinical use. In this study, we compared the generic beam data with the measured beam data to evaluate the reliability of generic beam data to be used for the clinical purpose. Methods and Material: PDDs and Profiles of Open and Wedge fields for different field sizes and at different depths measured as per Varian’s algorithm commissioning guideline. The measurement performed with PTW 3D-scanning water phantom with semi-flex ion chamber and MEPHYSTO software. The online available Varian Golden Beam Data compared with the measured data to evaluate the accuracy of the golden beam data to be used for the commissioning of Eclipse treatment planning system. Results: The deviation between measured vs. golden beam data was in the range of 2% max. In PDDs, the deviation increases more in the deeper depths than the shallower depths. Similarly, profiles have the same trend of increasing deviation at large field sizes and increasing depths. Conclusion: Study shows that the percentage deviation between measured and golden beam data is within the acceptable tolerance and therefore can be used for the commissioning process; however, verification of small subset of acquired data with the golden beam data should be mandatory before clinical use.

Keywords: percent depth dose, flatness, symmetry, golden beam data

Procedia PDF Downloads 453
769 Efficacy of Corticosteroids versus Placebo in Third Molar Surgery: A Systematic Review of Patient-Reported Outcomes

Authors: Parastoo Parhizkar, Jaber Yaghini, Omid Fakheran

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Background: Third molar surgery is often associated with postoperative problems which cause serious impediments on daily activities and quality of life. Steroidal anti-inflammatory drugs may decrease these common post-operative complications. The purpose of this review is evaluating the available evidence regarding the efficacy of corticosteroids used as adjunctive therapy for patients undergoing third molar surgery. Methods: PubMed, Google scholar, Scopus, web of science, clinicaltrials.gov, scirus.com, Cochrane central register for controlled trials, LILACS, OpenGrey, centerwatch, isrctn, who.int and ebsco were searched without restrictions regarding the year of publication. Randomized clinical trials assessing patient-reported outcomes in patients undergoing surgical therapy, were eligible for inclusion. Study quality was assessed using the CONSORT-checklist. No meta-analysis was performed. Results: A total of twelve Randomized Clinical Trials were included in this study. Methylprednisolone and Dexamethasone may decrease postoperative side effects such as pain, trismus and edema. Based on the results both of them could improve patients’ satisfaction, and there is no significant difference between these two types of corticosteroids regarding the patient centered outcomes (p > 0.05). Intralesional and intravenous injection of Dexamethasone showed an equivalent result, with statistically significant better results (P < 0.05) in comparison with the oral treatment. Conclusion: various types of corticosteroids can enhance the patient’s satisfaction following third molar surgery. However, there is no significant difference between Dexamethasone, Prednisolone and Methylprednisolone groups in this regard. Comparing the various administration routs, local injection of Dexamethasone is quite simple, painless and cost-effective adjunctive therapy with better drug efficacy.

Keywords: third molar surgery, corticosteroids, patient-reported outcomes, health related quality of life

Procedia PDF Downloads 177
768 Formulation Development, Process Optimization and Comparative study of Poorly Compressible Drugs Ibuprofen, Acetaminophen Using Direct Compression and Top Spray Granulation Technique

Authors: Abhishek Pandey

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Ibuprofen and Acetaminophen is widely used as prescription & non-prescription medicine. Ibuprofen mainly used in the treatment of mild to moderate pain related to headache, migraine, postoperative condition and in the management of spondylitis, osteoarthritis and rheumatoid arthritis. Acetaminophen is used as an analgesic and antipyretic drug. Ibuprofen having high tendency of sticking to punches of tablet punching machine while Acetaminophen is not ordinarily compressible to tablet formulation because Acetaminophen crystals are very hard and brittle in nature and fracture very easily when compressed producing capping and laminating tablet defects therefore wet granulation method is used to make them compressible. The aim of study was to prepare Ibuprofen and Acetaminophen tablets by direct compression and top spray granulation technique. In this Investigation tablets were prepared by using directly compressible grade excipients. Dibasic calcium phosphate, lactose anhydrous (DCL21), microcrystalline cellulose (Avicel PH 101). In order to obtain best or optimized formulation, nine different formulations were generated among them batch F7, F8, F9 shows good results and within the acceptable limit. Formulation (F7) selected as optimize product on the basis of dissolution study. Furtherly, directly compressible granules of both drugs were prepared by using top spray granulation technique in fluidized bed processor equipment and compressed .In order to obtain best product process optimization was carried out by performing four trials in which various parameters like inlet air temperature, spray rate, peristaltic pump rpm, % LOD, properties of granules, blending time and hardness were optimized. Batch T3 coined as optimized batch on the basis physical & chemical evaluation. Finally formulations prepared by both techniques were compared.

Keywords: direct compression, top spray granulation, process optimization, blending time

Procedia PDF Downloads 334