Search results for: drug use
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1960

Search results for: drug use

340 Justice and the Juvenile: Changing Trends and Developments

Authors: Shikhar Shrivastava, Varun Khare

Abstract:

Background: We are confronted by a society that is becoming more complex, more mobile, and more dysfunctional. Teen pregnancy, suicide, elopement, and the perusal of dangerous drugs have become commonplace. In addition, children do not settle their disputes as they once did. Guns and knives are quotidian. Therefore, it has been an exigent to have a "Juvenile Code" that would provide specific substantive and procedural rules for juveniles in the justice system. However, until the twentieth century, there was little difference between how the justice system treated adults and children. Age was considered only in terms of appropriate punishment and juveniles were eligible for the same punishment as adults. Findings: The increased prevalence and legislative support for specialized courts, Juvenile Justice Boards, including juvenile drug, mental health and truancy court programs, as well as diversion programs and evidence-based approaches into the fabric of juvenile justice are just a few examples of recent advances. In India, various measures were taken to prosecute young offenders who committed violent crimes as adults. But it was argued that equating juveniles with adult criminals was neither scientifically correct nor normatively defensible. It would defeat the very purpose of the justice system. Methodology and Conclusion: This paper attempts to bring forth the results of analytical and descriptive research that examined changing trends in juvenile justice legislation. It covers the investigative and inspective practices of police, the various administrative agencies who have roles in implementing the legislation, the courts, and the detention centers. In this paper we shall discuss about how the juvenile justice system is the dumping ground for many of a youths’ problem. The changing notions of justice, from retributive to restorative and rehabilitative shall be discussed. A comparative study of the Juvenile act in India and that of the U.S has been discussed. Specific social institutions and forces that explain juvenile delinquency are identified. In addition, various influences on juvenile delinquency are noted, such as families, schools, peer groups and communities. The text concludes by addressing socialization, deterrence, imprisonments, alternatives, restitution and preventions.

Keywords: juvenile, justice system, retributive, rehabilitative, delinquency

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339 Characterization of Antibiotic Resistance in Cultivable Enterobacteriaceae Isolates from Different Ecological Niches in the Eastern Cape, South Africa

Authors: Martins A. Adefisoye, Mpaka Lindelwa, Fadare Folake, Anthony I. Okoh

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Evolution and rapid dissemination of antibiotic resistance from one ecosystem to another has been responsible for wide-scale epidemic and endemic spreads of multi-drug resistance pathogens. This study assessed the prevalence of Enterobacteriaceae in different environmental samples, including river water, hospital effluents, abattoir wastewater, animal rectal swabs and faecal droppings, soil, and vegetables, using standard microbiological procedure. The identity of the isolates were confirmed using matrix-assisted laser desorption ionization-time of flight mass spectrophotometry (MALDI-TOF) while the isolates were profiled for resistance against a panel of 16 antibiotics using disc diffusion (DD) test, and the occurrence of resistance genes (ARG) was determined by polymerase chain reactions (PCR). Enterobacteriaceae counts in the samples range as follows: river water 4.0 × 101 – 2.0 × 104 cfu/100 ml, hospital effluents 1.5 × 103 – 3.0 × 107 cfu/100 ml, municipal wastewater 2.3 × 103 – 9.2 × 104 cfu/100 ml, faecal droppings 3.0 × 105 – 9.5 × 106 cfu/g, animal rectal swabs 3.0 × 102 – 2.9 × 107 cfu/ml, soil 0 – 1.2 × 105 cfu/g and vegetables 0 – 2.2 × 107 cfu/g. Of the 700 randomly selected presumptive isolates subjected to MALDI-TOF analysis, 129 (18.4%), 68 (9.7%), 67 (9.5%), 41 (5.9%) were E. coli, Klebsiella spp., Enterobacter spp., and Citrobacter spp. respectively while the remaining isolates belong to other genera not targeted in the study. The DD test shows resistance ranging between 91.6% (175/191) for cefuroxime and (15.2%, 29/191) for imipenem The predominant multiple antibiotic resistance phenotypes (MARP), (GM-AUG-AP-CTX-CXM-CIP-NOR-NI-C-NA-TS-T-DXT) occurred in 9 Klebsiella isolates. The multiple antibiotic resistance indices (MARI) the isolates (range 0.17–1.0) generally showed >95% had MARI above the 0.2 thresholds, suggesting that most of the isolates originate from high-risk environments with high antibiotic use and high selective pressure for the emergence of resistance. The associated ARG in the isolates include: bla TEM 61.9 (65), bla SHV 1.9 (2), bla OXA 8.6 (9), CTX-M-2 8.6 (9), CTX-M-9 6.7 (7), sul 2 26.7 (28), tet A 16.2 (17), tet M 17.1 (18), aadA 59.1 (62), strA 34.3 (36), aac(3)A 19.1 (20), (aa2)A 7.6 (8), and aph(3)-1A 10.5 (11). The results underscore the need for preventative measures to curb the proliferation of antibiotic-resistant bacteria including Enterobacteriaceae to protect public health.

Keywords: enterobacteriaceae, antibiotic-resistance, MALDI-TOF, resistance genes, MARP, MARI, public health

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338 Vitamin D Supplementation Potentiates the Clinical Benefits of Metformin and Pioglitazone in Indian Women with Polycystic Ovary Syndrome

Authors: Mohd Asharf Ganie, Aafia Rashid, Mohd Afzal Zargar, Showkat Ali Zargar, Syed Mudasar, Tabasum Parvaiz, Zafar Amin Shah

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Accumulating evidence suggests that Vitamin D deficiency (VDD) might at least contribute to the metabolic co-morbidities in PCOS. Hence, we aimed to study the effect of vitamin D supplementation in co-prescription with insulin sensitizers like metformin and pioglitazone on clinical, hormonal and metabolic parameters in women with PCOS. In this open label randomized, controlled trial a total of 120 women with PCOS diagnosis (AE-PCOS 2009 Criteria) were assigned to four treatment groups (n= 30 in each): group I (metformin 1 gm/day in combination with cholecalciferol 4000 IU/day), group II (pioglitazone 30 mg/day in combination with cholecalciferol 4000 IU/day), group III (metformin 1 gm /day) and group IV (pioglitazone 30 mg/day). Vitamin D supplementation was given as 60,000 units every two weeks for 24 weeks. All the subjects were routinely evaluated for clinical, biochemical, hormonal and insulin sensitivity parameters in addition to various safety parameters especially serum calcium levels at baseline and after 24 weeks of the treatment. Our results indicate that 95.5% of PCOS women were vitamin D deficient at baseline. Serum 25 (OH) D levels increased significantly (p < 0.001) in groups I and II without any adverse effects after 24 weeks of oral administration of 4000 IU cholecalciferol daily. However, serum 25 (OH) D levels remained unchanged in group III and IV. By six months, number of menstrual cycles per year increased whereas Ferriman-Gallwey score, serum total testosterone and HOMA-IR decreased significantly (P < 0.001) in the treatment groups supplemented with cholecalciferol as compared to those treated either drug alone. No significant beneficial changes were observed on weight, BMI, blood pressure, glucose tolerance and serum lipids in any of the groups supplemented with cholecalciferol. We conclude that daily dose of 4000 IU cholecalciferol might be a useful adjunct in complex treatment of PCOS with fewer adverse events. Furthermore, pioglitazone and cholecalciferol combination seems to be marginally better although there was no statistical significance.

Keywords: PCOS, vitamin D supplementation, insulin resistance, spironolactone, metformin, pioglitazone

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337 Critical Assessment of Herbal Medicine Usage and Efficacy by Pharmacy Students

Authors: Anton V. Dolzhenko, Tahir Mehmood Khan

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An ability to make an evidence-based decision is a critically important skill required for practicing pharmacists. The development of this skill is incorporated into the pharmacy curriculum. We aimed in our study to estimate perception of pharmacy students regarding herbal medicines and their ability to assess information on herbal medicines professionally. The current Monash University curriculum in Pharmacy does not provide comprehensive study material on herbal medicines and students should find their way to find information, assess its quality and make a professional decision. In the Pharmacy course, students are trained how to apply this process to conventional medicines. In our survey of 93 undergraduate students from year 1-4 of Pharmacy course at Monash University Malaysia, we found that students’ view on herbal medicines is sometimes associated with common beliefs, which affect students’ ability to make evidence-based conclusions regarding the therapeutic potential of herbal medicines. The use of herbal medicines is widespread and 95.7% of the participated students have prior experience of using them. In the scale 1 to 10, students rated the importance of acquiring herbal medicine knowledge for them as 8.1±1.6. More than half (54.9%) agreed that herbal medicines have the same clinical significance as conventional medicines in treating diseases. Even more, students agreed that healthcare settings should give equal importance to both conventional and herbal medicine use (80.6%) and that herbal medicines should comply with strict quality control procedures as conventional medicines (84.9%). The latter statement also indicates that students consider safety issues associated with the use of herbal medicines seriously. It was further confirmed by 94.6% of students saying that the safety and toxicity information on herbs and spices are important to pharmacists and 95.7% of students admitting that drug-herb interactions may affect therapeutic outcome. Only 36.5% of students consider herbal medicines as s safer alternative to conventional medicines. The students use information on herbal medicines from various sources and media. Most of the students (81.7%) obtain information on herbal medicines from the Internet and only 20.4% mentioned lectures/workshop/seminars as a source of such information. Therefore, we can conclude that students attained the skills on the critical assessment of therapeutic properties of conventional medicines have a potential to use their skills for evidence-based decisions regarding herbal medicines.

Keywords: evidence-based decision, pharmacy education, student perception, traditional medicines

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336 Constraint-Based Computational Modelling of Bioenergetic Pathway Switching in Synaptic Mitochondria from Parkinson's Disease Patients

Authors: Diana C. El Assal, Fatima Monteiro, Caroline May, Peter Barbuti, Silvia Bolognin, Averina Nicolae, Hulda Haraldsdottir, Lemmer R. P. El Assal, Swagatika Sahoo, Longfei Mao, Jens Schwamborn, Rejko Kruger, Ines Thiele, Kathrin Marcus, Ronan M. T. Fleming

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Degeneration of substantia nigra pars compacta dopaminergic neurons is one of the hallmarks of Parkinson's disease. These neurons have a highly complex axonal arborisation and a high energy demand, so any reduction in ATP synthesis could lead to an imbalance between supply and demand, thereby impeding normal neuronal bioenergetic requirements. Synaptic mitochondria exhibit increased vulnerability to dysfunction in Parkinson's disease. After biogenesis in and transport from the cell body, synaptic mitochondria become highly dependent upon oxidative phosphorylation. We applied a systems biochemistry approach to identify the metabolic pathways used by neuronal mitochondria for energy generation. The mitochondrial component of an existing manual reconstruction of human metabolism was extended with manual curation of the biochemical literature and specialised using omics data from Parkinson's disease patients and controls, to generate reconstructions of synaptic and somal mitochondrial metabolism. These reconstructions were converted into stoichiometrically- and fluxconsistent constraint-based computational models. These models predict that Parkinson's disease is accompanied by an increase in the rate of glycolysis and a decrease in the rate of oxidative phosphorylation within synaptic mitochondria. This is consistent with independent experimental reports of a compensatory switching of bioenergetic pathways in the putamen of post-mortem Parkinson's disease patients. Ongoing work, in the context of the SysMedPD project is aimed at computational prediction of mitochondrial drug targets to slow the progression of neurodegeneration in the subset of Parkinson's disease patients with overt mitochondrial dysfunction.

Keywords: bioenergetics, mitochondria, Parkinson's disease, systems biochemistry

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335 Role of Imaging in Alzheimer's Disease Trials: Impact on Trial Planning, Patient Recruitment and Retention

Authors: Kohkan Shamsi

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Background: MRI and PET are now extensively utilized in Alzheimer's disease (AD) trials for patient eligibility, efficacy assessment, and safety evaluations but including imaging in AD trials impacts site selection process, patient recruitment, and patient retention. Methods: PET/MRI are performed at baseline and at multiple follow-up timepoints. This requires prospective site imaging qualification, evaluation of phantom data, training and continuous monitoring of machines for acquisition of standardized and consistent data. This also requires prospective patient/caregiver training as patients must go to multiple facilities for imaging examinations. We will share our experience form one of the largest AD programs. Lesson learned: Many neurological diseases have a similar presentation as AD or could confound the assessment of drug therapy. The inclusion of wrong patients has ethical and legal issues, and data could be excluded from the analysis. Centralized eligibility evaluation read process will be discussed. Amyloid related imaging abnormalities (ARIA) were observed in amyloid-β trials. FDA recommended regular monitoring of ARIA. Our experience in ARIA evaluations in large phase III study at > 350 sites will be presented. Efficacy evaluation: MRI is utilized to evaluate various volumes of the brain. FDG PET or amyloid PET agents has been used in AD trials. We will share our experience about site and central independent reads. Imaging logistic issues that need to be handled in the planning phase will also be discussed as it can impact patient compliance thereby increasing missing data and affecting study results. Conclusion: imaging must be prospectively planned to include standardizing imaging methodologies, site selection process and selecting assessment criteria. Training should be transparently conducted and documented. Prospective patient/caregiver awareness of imaging requirement is essential for patient compliance and reduction in missing imaging data.

Keywords: Alzheimer's disease, ARIA, MRI, PET, patient recruitment, retention

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334 Synthesis and Optimization of Bio Metal-Organic Framework with Permanent Porosity

Authors: Tia Kristian Tajnšek, Matjaž Mazaj, Nataša Zabukovec Logar

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Metal-organic frameworks (MOFs) with their specific properties and the possibility of tuning the structure represent excellent candidates for use in the biomedical field. Their advantage lies in large pore surfaces and volumes, as well as the possibility of using bio-friendly or bioactive constituents. So-called bioMOFs are representatives of MOFs, which are constructed from at least one biomolecule (metal, a small bioactive molecule in metal clusters and/or linker) and are intended for bio-application (usually in the field of medicine; most commonly drug delivery). When designing a bioMOF for biomedical applications, we should adhere to some guidelines for an improved toxicological profile of the material. Such as (i) choosing an endogenous/nontoxic metal, (ii) GRAS (generally recognized as safe) linker, and (iii) nontoxic solvents. Design and synthesis of bioNICS-1 (bioMOF of National Institute of Chemistry Slovenia – 1) consider all these guidelines. Zinc (Zn) was chosen as an endogenous metal with an agreeable recommended daily intake (RDI) and LD50 value, and ascorbic acid (Vitamin C) was chosen as a GRAS and active linker. With these building blocks, we have synthesized a bioNICS-1 material. The synthesis was done in ethanol using a solvothermal method. The synthesis protocol was further optimized in three separate ways. Optimization of (i) synthesis parameters to improve the yield of the synthesis, (ii) input reactant ratio and addition of specific modulators for production of larger crystals, and (iii) differing of the heating source (conventional, microwave and ultrasound) to produce nano-crystals. With optimization strategies, the synthesis yield was increased. Larger crystals were prepared for structural analysis with the use of a proper species and amount of modulator. Synthesis protocol was adjusted to different heating sources, resulting in the production of nano-crystals of bioNICS-1 material. BioNICS-1 was further activated in ethanol and structurally characterized, resolving the crystal structure of new material.

Keywords: ascorbic acid, bioMOF, MOF, optimization, synthesis, zinc ascorbate

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333 The Potential of Acanthaster Plancii Fractions as Anti-Atherosclerotic Agent by Inhibiting the Expression of Proprotein Convertase Subtilisin-Kexin Type 9

Authors: Nurjannatul Naim Kamaruddin, Tengku Sifziuzl Tengku Muhammad, Aina Farahiyah Abdul Manan, Habsah Mohamad

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Atherosclerosis which leads to cardiovascular diseases such as myocardial infarction, unstable angina (ischemic heart pain), sudden cardiac death and stroke is the principal cause of death worldwide. It has been a very critical issue as current common drug treatment, statin therapy has left bad side effects like rhabdomyolysis, atrial fibrillation, liver disease, abdominal and chest pain. Interestingly, the discoveries of proprotein convertase subtilisin-kexin type 9 have paved a new way in the treatment of atherosclerosis. This serine protease is believed to involve in the regulation of LDL- uptake by LDL-receptor. Therefore, this study was conducted to evaluate the potential of Acanthaster plancii fractions to reduce the transcriptional activity of the PCSK9 promoter. In this study, the marine organism which is Acanthaster plancii has been used as the source for marine compounds in inhibiting PCSK9. The cytotoxicity activity of ten fractions from the methanol extracts of Acanthaster plancii was investigated on HepG2 cell lines using MTS assay and dual glo luciferase assay was carried out later to analyses the effects of the samples in reducing the transcriptional activity of the PCSK9 promoter. Both assays used fractions with five different concentrations, 3.13µg/mL, 6.25µg/mL, 12.5µg/mL, 25µg/mL, and 50µg/mL. MTS assay indicated that the fractions are non-cytotoxic towards HepG2 cell lines as their IC50 value is greater than 30µg/mL. Whilst, for the dual glo luciferase assay, among all the fractions, Enhance Fraction 2 (EF2) showed the best potential in reducing the transcriptional activity of the PCSK9 promoter. The results indicated that this EF2 gave the lowest PCSK9 promoter expression at low concentration which is 0.2 fold change at 6.25µg/mL. This finding suggested that further analysis should be done to validate the potential of Acanthaster plancii as the source of anti-atherosclerotic agent.

Keywords: Acanthaster plancii, atherosclerosis, luciferase assay, PCSK9

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332 Surface Modification of Co-Based Nanostructures to Develop Intrinsic Fluorescence and Catalytic Activity

Authors: Monalisa Pal, Kalyan Mandal

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Herein we report the molecular functionalization of promising transition metal oxide nanostructures, such as Co3O4 nanocubes, using nontoxic and biocompati-ble organic ligand sodium tartrate. The electronic structural modification of the nanocubes imparted through functionalization and subsequent water solubilization reveals multiple absorption bands in the UV-vis region. Further surface modification of the solubilized nanocubes, leads to the emergence of intrinsic multi-color fluorescence (from blue, cyan, green to red region of the spectrum), upon excitation at proper wavelengths, where the respective excitation wavelengths have a direct correlation with the observed UV-vis absorption bands. Using a multitude of spectroscopic tools we have investigated the mechanistic insight behind the origin of different UV-vis absorption bands and emergence of multicolor photoluminescence from the functionalized nanocubes. Our detailed study shows that ligand to metal charge transfer (LMCT) from tartrate ligand to Co2+/Co3+ ions and d-d transitions involving Co2+/Co3+ ions are responsible for generation of this novel optical properties. Magnetic study reveals that, antiferromagnetic nature of Co3O4 nanocubes changes to ferromagnetic behavior upon functionalization, however, the overall magnetic response was very weak. To combine strong magnetism with this novel optical property, we followed the same surface modification strategy in case of CoFe2O4 nanoparticles, which reveals that irrespective of size and shape, all Co-based oxides can develop intrinsic multi-color fluorescence upon facile functionalization with sodium tartrate ligands and the magnetic response was significantly higher. Surface modified Co-based oxide nanostructures also show excellent catalytic activity in degradation of biologically and environmentally harmful dyes. We hope that, our developed facile functionalization strategy of Co-based oxides will open up new opportunities in the field of biomedical applications such as bio-imaging and targeted drug delivery.

Keywords: co-based oxide nanostructures, functionalization, multi-color fluorescence, catalysis

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331 Positive Effects of Aerobic Exercise after Bone Marrow Stem Cell Transplantation on Recovery of Dopaminergic Neurons and Promotion of Angiogenesis Markers in the Striatum of Parkinsonian Rats

Authors: S. A. Hashemvarzi, A. Heidarianpour, Z. Fallahmohammadi, M. Pourghasem, M. Kaviani

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Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative in the central nervous system characterized by the loss of dopaminergic neurons in the substantia nigra resulting in loss of dopamine release in the striatum. Non-drug treatment options such as Stem cell transplantation and exercise have been considered for treatment of Parkinson's disease. Purpose: The purpose of this study was to evaluate the effect of aerobic exercise after bone marrow stem cells transplantation on recovery of dopaminergic neurons and promotion of angiogenesis markers in the striatum of parkinsonian rats. Materials and Methods: 42 male Wistar rats were divided randomly into six groups: Normal (N), Sham (S), Parkinson’s (P), Stem cells transplanted Parkinson’s (SP), Exercised Parkinson’s (EP) and Stem cells transplanted + Exercised Parkinson’s (SEP). To create a model of Parkinson's, the striatum was destroyed by injection of 6-hydroxy-dopamine into the striatum through stereotaxic apparatus. Stem cells were derived from the bone marrow of femur and tibia of male rats with 6-8 weeks old. After cultivation, approximately 5×105 cells in 5 microliter of medium were injected into the striatum of rats through the channel. Aerobic exercise was included 8 weeks of running on the treadmill with a speed of 15 meters per minute. At the end, all subjects were decapitated and striatum tissues were separately isolated for measurement of vascular endothelial growth factor (VEGF), dopamine (DA) and tyrosine hydroxylase (TH) levels. Results: VEGF, DA and TH levels in the striatum of parkinsonian rats significantly increased in treatment groups (SP, EP and SEP), especially in SEP group compared to P group after treatment (P<0.05). Conclusion: The findings implicate that the BMSCs transplantation in combination with exercise would have synergistic effects leading to functional recovery, dopaminergic neurons recovery and promotion of angiogenesis marker in the striatum of parkinsonian rats.

Keywords: stem cells, treadmill training, neurotrophic factors, Parkinson

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330 Protective Efficacy of Moringa oleifera against Oxidative Ovarian Damage and Reproductive Failure in Female Rats Caused by Cyclophosphamide

Authors: Seham Samir Soliman, Ahmed A.Suliman, Khaled Fathy, Ahmed A. Sedik

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Cyclophosphamide (CP), an antineoplastic drug, has been found to induce reproductive damage. It is essential to develop approaches aimed at safeguarding ovarian tissue integrity in women experiencing reproductive toxicity as a result of chemotherapy. The current study was conducted to assess the impact of an extract derived from Moringa oleifera (M. oleifera) leaves on ovarian damage produced by CP. A total of 32 female Wistar Albino rats, which were in a healthy cycling state, were randomly separated into 4 groups, with every group contains 8 rats. The first group was administered intraperitoneal (i.p.) saline. The second group was administered a solitary intraperitoneal dosage of cyclophosphamide (200 mg/kg). The third one received M. oleifera extract (150 mg/kg orally) for 20 days, followed by i.p. of CP on the last day of the experiment. The fourth group received M. oleifera extract (250 mg/kg orally) for 20 days, followed by i.p. of CP on the last day of the experiment. Hormonal assessments, including luteinizing hormone (LH), estrogen (ES), and follicle-stimulating hormone (FSH), were performed 24 hours after CP administration. In addition, evaluating the antioxidant status and inflammatory response against CP. Moreover, conducting detailed histopathological and ultra-structural pictures of the ovary. Our findings reported that rats intoxicated with CP exhibited elevated levels of FSH, LH, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and a decrease in E₂, and glutathione (GSH) levels. Pre-treatment with M. oleifera extract (250 mg/kg orally) ameliorated the disturbance in hormonal changes, oxidative stress indices, and the levels of pro-inflammatory mediators. Also, the histopathological and ultra-structural pictures of the ovaries were improved significantly in rats. In conclusion, M. oleifera extract possesses a significant protective role against CP-induced acute reproductive toxicity via modulating the values of FSH, LH, E₂ and quenching the release of reactive oxygen species and inflammatory mediators in female rats.

Keywords: cyclophosphamide, Moringa oleifera, ovarian function, oxidative stress, pro-inflammatory mediators

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329 Comparison of 18F-FDG and 11C-Methionine PET-CT for Assessment of Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Carcinoma

Authors: Sonia Mahajan Dinesh, Anant Dinesh, Madhavi Tripathi, Vinod Kumar Ramteke, Rajnish Sharma, Anupam Mondal

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Background: Neo-adjuvant chemotherapy plays an important role in treatment of breast cancer by decreasing the tumour load and it offers an opportunity to evaluate response of primary tumour to chemotherapy. Standard anatomical imaging modalities are unable to accurately reflect the response to chemotherapy until several cycles of drug treatment have been completed. Metabolic imaging using tracers like 18F-fluorodeoxyglucose (FDG) as a marker of glucose metabolism or amino acid tracers like L-methyl-11C methionine (MET) have potential role for the measurement of treatment response. In this study, our objective was to compare these two PET tracers for assessment of response to neoadjuvant chemotherapy, in locally advanced breast carcinoma. Methods: In our prospective study, 20 female patients with histology proven locally advanced breast carcinoma underwent PET-CT imaging using FDG and MET before and after three cycles of neoadjuvant chemotherapy (CAF regimen). Thereafter, all patients were taken for MRM and the resected specimen was sent for histo-pathological analysis. Tumour response to the neoadjuvant chemotherapy was evaluated by PET-CT imaging using PERCIST criteria and correlated with histological results. Responses calculated were compared for statistical significance using paired t- test. Results: Mean SUVmax for primary lesion in FDG PET and MET PET was 15.88±11.12 and 5.01±2.14 respectively (p<0.001) and for axillary lymph nodes was 7.61±7.31 and 2.75±2.27 respectively (p=0.001). Statistically significant response in primary tumour and axilla was noted on both FDG and MET PET after three cycles of NAC. Complete response in primary tumour was seen in only 1 patient in FDG and 7 patients in MET PET (p=0.001) whereas there was no histological complete resolution of tumor in any patient. Response to therapy in axillary nodes noted on both PET scans were similar (p=0.45) and correlated well with histological findings. Conclusions: For the primary breast tumour, FDG PET has a higher sensitivity and accuracy than MET PET and for axilla both have comparable sensitivity and specificity. FDG PET shows higher target to background ratios so response is better predicted for primary breast tumour and axilla. Also, FDG-PET is widely available and has the advantage of a whole body evaluation in one study.

Keywords: 11C-methionine, 18F-FDG, breast carcinoma, neoadjuvant chemotherapy

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328 Simulation of the FDA Centrifugal Blood Pump Using High Performance Computing

Authors: Mehdi Behbahani, Sebastian Rible, Charles Moulinec, Yvan Fournier, Mike Nicolai, Paolo Crosetto

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Computational Fluid Dynamics blood-flow simulations are increasingly used to develop and validate blood-contacting medical devices. This study shows that numerical simulations can provide additional and accurate estimates of relevant hemodynamic indicators (e.g., recirculation zones or wall shear stresses), which may be difficult and expensive to obtain from in-vivo or in-vitro experiments. The most recent FDA (Food and Drug Administration) benchmark consisted of a simplified centrifugal blood pump model that contains fluid flow features as they are commonly found in these devices with a clear focus on highly turbulent phenomena. The FDA centrifugal blood pump study is composed of six test cases with different volumetric flow rates ranging from 2.5 to 7.0 liters per minute, pump speeds, and Reynolds numbers ranging from 210,000 to 293,000. Within the frame of this study different turbulence models were tested including RANS models, e.g. k-omega, k-epsilon and a Reynolds Stress Model (RSM) and, LES. The partitioners Hilbert, METIS, ParMETIS and SCOTCH were used to create an unstructured mesh of 76 million elements and compared in their efficiency. Computations were performed on the JUQUEEN BG/Q architecture applying the highly parallel flow solver Code SATURNE and typically using 32768 or more processors in parallel. Visualisations were performed by means of PARAVIEW. Different turbulence models including all six flow situations could be successfully analysed and validated against analytical considerations and from comparison to other data-bases. It showed that an RSM represents an appropriate choice with respect to modeling high-Reynolds number flow cases. Especially, the Rij-SSG (Speziale, Sarkar, Gatzki) variant turned out to be a good approach. Visualisation of complex flow features could be obtained and the flow situation inside the pump could be characterized.

Keywords: blood flow, centrifugal blood pump, high performance computing, scalability, turbulence

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327 In vitro and in vivo Potential Effect of the N-Acylsulfonamide Bis-oxazolidin-2-ones on Toxoplasma gondii

Authors: Benlaifa Meriem, Berredjem Hajira, Bouasla Radia, Berredjem Malika, Djebar Med Reda

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Toxoplasmosis is a cosmopolitan infection due to Toxoplasma gondii (T.gondii). It is a significant cause of congenital disease and an important opportunistic pathogen which has become a worldwide increasing problem due to the AIDS epidemic. Current available drugs do not give satisfactory results and often have only a static and several adverse side effects as it is the case of pyrimethamine. So, the need to develop and evaluate new drugs is critical. The purpose of this study is to investigate the in vitro and in vivo effects of the new chiral N-acylsulfonamide bis-oxazolidin-2-ones on T.gondii. In this study, anti-T.gondii RH strain activities, of two new chiral N-acylsulfonamide bis-oxazolidin-2-ones were evaluated in vitro, using a MRC-5 fibroblast tissue cultures to determine the concentration that inhibit parasite multiplication by 50% (IC50) of each drug and in vivo, by PCR detection of the tachyzoites in mice ascites after new molecules treatment, using the 35-fold repetitive B1 gene of T.gondii. The in vitro results demonstrated that the treatment with the tested molecules decreased the amount of tachyzoites in cell culture in a dose-dependent manner. The inhibition was complete for concentrations over 4 mg/ml. The IC50 of Mol 1 and Mol 2 were 1.5 and 3 mg/ml, respectively, and were quite similar to the control one (2 mg/ml). The Mol 1 was highly active against T.gondii in cell cultures than Mol 2; these results were similar to those of sulfadiazine-treated group (p < 0.05). Toxoplasma-specific DNA was demonstrated in all ascites samples from infected mice of the different tested groups. Mol 1 showed better effect than Mol 2, but it did not completely inhibit the parasite proliferation. The intensity of amplification products increased when the treatment started late after infection. These findings suggest continuous parasite replication despite the treatment. In conclusion, our results showed a promising treatment effect of the tested molecules and suggest that in vitro, the Mol 1, and Mol 2 have a dose-dependent effect and a high cytotoxicity on the studied cells. The present study revealed that concentration and duration of tested molecules treatment are major factors that influence the course of Toxoplasma infection in infected mice.

Keywords: cytotoxicity, PCR, sulfonamide, Toxoplasma gondii

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326 Targeting Glucocorticoid Receptor Eliminate Dormant Chemoresistant Cancer Stem Cells in Glioblastoma

Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.

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325 Effect of Lowering the Proportion of Chlorella vulgaris in Fish Feed on Tilapia's Immune System

Authors: Hamza A. Pantami, Khozizah Shaari, Intan S. Ismail, Chong C. Min

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Introduction: Tilapia is the second-highest harvested freshwater fish species in Malaysia, available in almost all fish farms and markets. Unfortunately, tilapia culture in Malaysia is highly affected by Aeromonas hydrophila and Streptococcus agalactiae, which affect the production rate and consequently pose a direct negative economic impact. Reliance on drugs to control or reduce bacterial infections has been led to contamination of water bodies and development of drug resistance, as well as gave rise to toxicity issues in downstream fish products. Resorting to vaccines have helped curb the problem to a certain extent, but a more effective solution is still required. Using microalgae-based feed to enhance the fish immunity against bacterial infection offers a promising alternative. Objectives: This study aims to evaluate the efficacy of Chlorella vulgaris at lower percentage incorporation in feeds for an immune boost of tilapia in a shorter time. Methods: The study was in two phases. The safety concentration studies at 500 mg/kg-1 and the administration of cultured C. vulgaris biomass via incorporation into fish feed for five different groups in three weeks. Group 1 was the control (0% incorporation), whereas group 2, 3, 4 and 5 received 0.625%, 1.25%, 2.5% and 5% incorporation respectively. The parameters evaluated were the blood profile, serum lysozyme activity (SLA), serum bactericidal activity (SBA), phagocytosis activity (PA), respiratory burst activity (RBA), and lymphoproliferation activity (LPA). The data were analyzed via ANOVA using SPSS (version 16). Further testing was done using Tukey’s test. All tests were performed at the 95% confidence interval (p < 0.05). Results: There were no toxic signs in tilapia fish at 500 mg/kg-1. Treated groups showed significantly better immune parameters compared to the control group (p < 0.05). Conclusions: C. vulgaris crude biomass in a fish meal at a lower incorporation level of 5% can increase specific and non-specific immunity in tilapia fish in a shorter time duration.

Keywords: Chlorella vulgaris, hematology profile, immune boost, lymphoproliferation

Procedia PDF Downloads 79
324 Effect of Aquatic Seed Extract of (Cichorium intybus L.) and Metformin on Nitric Oxide in Type 2 Diabetic Rats

Authors: Lotfollah Rezagholizadeh

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Background and Aim: Diabetes mellitus is related to high mortality and morbidity caused by the early development of atherosclerosis correlated to diabetic macroangiopathy. The endothelium-derived vasodilator, nitric oxide (NO) has been implicated in the development of vascular complications via the regulation of blood flow, and various antiatherosclerotic actions. Patients with type 2 diabetes (T2D) have a decreased level of endothelial nitric oxide release. In this study we aimed to examine the effect of aquatic seed extract of Cichorium intybus L. (chicory) and metformin (a known prescription drug for diabetes) on NO levels in T2D rats. Methods: Five groups of adult male Wistar rats were used (n=6): Non-diabetic controls without extract treatment (Control), Non-diabetic controls with extract treatment (Chicory-control), T2D rats without extract treatment (NIA/STZ), T2D rats treated with the extract (Chicory-NIA/STZ), and T2D groups that received metformin (100 mg/kg) but no extract (Metformin-NIA/STZ). T2D was induced with intraperitoneal (i.p) injection of niacinamide (NIA, 200 mg/kg), 15 min after an i.p administration of streptozotocin (STZ, 55 mg/kg). Lyophilized chicory extract (125 mg/kg) was dissolved in 0.2 ml normal saline and administered one dose a day. The experiments lasted for 3 weeks after the diabetes induction. NO analysis was performed by assay based on the Griess reaction. Data were reported as the mean ± SD and statistical analysis was performed by ANOVA. Results: Serum nitric oxide levels decreased significantly in NIA/STZ group compared with Control and Chicory-control. Treatment with chicory extract caused a significant increase in serum levels of NO in Chicory-NIA/STZ group compare to NIA/STZ group (p<05). Metformin-NIA/STZ group did not show considerable difference when compared with NIA/STZ, with respect to NO levels. In a group of rats made diabetic by STZ alone (type 1 diabetic rats, T1D), chicory did not have a significant ameliorating effect. Conclusion: In this study, we clearly showed a relationship between low serum nitric oxide levels and diabetes mellitus in rats. The increase in serum nitric oxide by chicory extract is an indication of antiatherogenic effect of this plant. Chicory seed extract was more efficient than metformin in improving the NO levels in NO-deficient T2D diabetic rats.

Keywords: type 2 diabetes mellitus, nitric oxide, chicory, metformin

Procedia PDF Downloads 303
323 Development of PVA/polypyrrole Scaffolds by Supercritical CO₂ for Its Application in Biomedicine

Authors: Antonio Montes, Antonio Cozar, Clara Pereyra, Diego Valor, Enrique Martinez de la Ossa

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Tissues and organs can be damaged because of traumatism, congenital illnesses, or cancer and the traditional therapeutic alternatives, such as surgery, cannot usually completely repair the damaged tissues. Tissue engineering allows regeneration of the patient's tissues, reducing the problems caused by the traditional methods. Scaffolds, polymeric structures with interconnected porosity, can be promoted the proliferation and adhesion of the patient’s cells in the damaged area. Furthermore, by means of impregnation of the scaffold with beneficial active substances, tissue regeneration can be induced through a drug delivery process. The objective of the work is the fabrication of a PVA scaffold coated with Gallic Acid and polypyrrole through a one-step foaming and impregnation process using the SSI technique (Supercritical Solvent Impregnation). In this technique, supercritical CO₂ penetrates into the polymer chains producing the plasticization of the polymer. In the depressurization step a CO₂ cellular nucleation and growing to take place to an interconnected porous structure of the polymer. The foaming process using supercritical CO₂ as solvent and expansion agent presents advantages compared to the traditional scaffolds’ fabrication methods, such as the polymer’s high solubility in the solvent or the possibility of carrying out the process at a low temperature, avoiding the inactivation of the active substance. In this sense, the supercritical CO₂ avoids the use of organic solvents and reduces the solvent residues in the final product. Moreover, this process does not require long processing time that could cause the stratification of substance inside the scaffold reducing the therapeutic efficiency of the formulation. An experimental design has been carried out to optimize the SSI technique operating conditions, as well as a study of the morphological characteristics of the scaffold for its use in tissue engineerings, such as porosity, conductivity or the release profiles of the active substance. It has been proved that the obtained scaffolds are partially porous, conductors of electricity and are able to release Gallic Acid in the long term.

Keywords: scaffold, foaming, supercritical, PVA, polypyrrole, gallic acid

Procedia PDF Downloads 152
322 Impact of 99mTc-MDP Bone SPECT/CT Imaging in Failed Back Surgery Syndrome

Authors: Ching-Yuan Chen, Lung-Kwang Pan

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Objective: Back pain is a major health problem costing billions of health budgets annually in Taiwan. Thousands of back pain surgeries are performed annually with up to 40% of patients complaining of back pain at time of post-surgery causing failed back surgery syndrome (FBSS), although diagnosis in these patients may be complex. The aim of study is to assess the feasibility of using bone SPECT-CT imaging to localize the active lesions causing persistent, recurrent or new backache after spine surgery. Materials and Methods: Bone SPECT-CT imaging was performed after the intravenous injection of 20 mCi of 99mTc-MDP for all the patients with diagnosis of FBSS. Patients were evaluated using status of subjectively pain relief, functional improvement and degree of satisfaction by reviewing the medical records and questionnaires in a 2 more years’ follow-up. Results: We enrolled a total of 16 patients were surveyed in our hospital from Jan. 2015 to Dec. 2016. Four people on SPEC/CT imaging ensured significant lesions were undergone a revised surgery (surgical treatment group). The mean visual analogue scale (VAS) decreased 5.3 points and mean Oswestry disability index (ODI) improved 38 points in the surgical group. The remaining 12 on SPECT/CT imaging were diagnosed as no significant lesions then received drug treatment (medical treatment group). The mean VAS only decreased 2 .1 point and mean ODI improved 12.6 points in the medical treatment group. In the posttherapeutic evaluation, the pain of the surgical treatment group showed a satisfactory improvement. In the medical treatment group, 10 of the 12 were also satisfied with the symptom relief while the other 2 did not improve significantly. Conclusions: Findings on SPECT-CT imaging appears to be easily explained the patients' pain. We recommended that SPECT/CT imaging was a feasible and useful clinical tool to improve diagnostic confidence or specificity when evaluating patients with FBSS.

Keywords: failed back surgery syndrome, oswestry disability index, SPECT-CT imaging, 99mTc-MDP, visual analogue scale

Procedia PDF Downloads 143
321 Hybrid Nanostructures of Acrylonitrile Copolymers

Authors: A. Sezai Sarac

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Acrylonitrile (AN) copolymers with typical comonomers of vinyl acetate (VAc) or methyl acrylate (MA) exhibit better mechanical behaviors than its homopolymer. To increase processability of conjugated polymer, and to obtain a hybrid nano-structure multi-stepped emulsion polymerization was applied. Such products could be used in, i.e., drug-delivery systems, biosensors, gas-sensors, electronic compounds, etc. Incorporation of a number of flexible comonomers weakens the dipolar interactions among CN and thereby decreases melting point or increases decomposition temperatures of the PAN based copolymers. Hence, it is important to consider the effect of comonomer on the properties of PAN-based copolymers. Acrylonitrile vinylacetate (AN–VAc ) copolymers have the significant effect to their thermal behavior and are also of interest as precursors in the production of high strength carbon fibers. AN is copolymerized with one or two comonomers, particularly with vinyl acetate The copolymer of AN and VAc can be used either as a plastic (VAc > 15 wt %) or as microfibers (VAc < 15 wt %). AN provides the copolymer with good processability, electrochemical and thermal stability; VAc provides the mechanical stability. The free radical copolymerization of AN and VAc copolymer and core Shell structure of polyprrole composites,and nanofibers of poly(m-anthranilic acid)/polyacrylonitrile blends were recently studied. Free radical copolymerization of acrylonitrile (AN) – with different comonomers, i.e. acrylates, and styrene was realized using ammonium persulfate (APS) in the presence of a surfactant and in-situ polymerization of conjugated polymers was performed in this reaction medium to obtain core-shell nano particles. Nanofibers of such nanoparticles were obtained by electrospinning. Morphological properties of nanofibers are investigated by scanning electron microscopy (SEM) and atomic force spectroscopy (AFM). Nanofibers are characterized using Fourier Transform Infrared - Attenuated Total Reflectance spectrometer (FTIR-ATR), Nuclear Magnetic Resonance Spectroscopy (1H-NMR), differential scanning calorimeter (DSC), thermal gravimetric analysis (TGA), and Electrochemical Impedance Spectroscopy. The electrochemical Impedance results of the nanofibers were fitted to an equivalent curcuit by modelling (ECM).

Keywords: core shell nanoparticles, nanofibers, ascrylonitile copolymers, hybrid nanostructures

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320 Epigenetic Modifying Potential of Dietary Spices: Link to Cure Complex Diseases

Authors: Jeena Gupta

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In the today’s world of pharmaceutical products, one should not forget the healing properties of inexpensive food materials especially spices. They are known to possess hidden pharmaceutical ingredients, imparting them the qualities of being anti-microbial, anti-oxidant, anti-inflammatory and anti-carcinogenic. Further aberrant epigenetic regulatory mechanisms like DNA methylation, histone modifications or altered microRNA expression patterns, which regulates gene expression without changing DNA sequence, contribute significantly in the development of various diseases. Changing lifestyles and diets exert their effect by influencing these epigenetic mechanisms which are thus the target of dietary phytochemicals. Bioactive components of plants have been in use since ages but their potential to reverse epigenetic alterations and prevention against diseases is yet to be explored. Spices being rich repositories of many bioactive constituents are responsible for providing them unique aroma and taste. Some spices like curcuma and garlic have been well evaluated for their epigenetic regulatory potential, but for others, it is largely unknown. We have evaluated the biological activity of phyto-active components of Fennel, Cardamom and Fenugreek by in silico molecular modeling, in vitro and in vivo studies. Ligand-based similarity studies were conducted to identify structurally similar compounds to understand their biological phenomenon. The database searching has been done by using Fenchone from fennel, Sabinene from cardamom and protodioscin from fenugreek as a query molecule in the different small molecule databases. Moreover, the results of the database searching exhibited that these compounds are having potential binding with the different targets found in the Protein Data Bank. Further in addition to being epigenetic modifiers, in vitro study had demonstrated the antimicrobial, antifungal, antioxidant and cytotoxicity protective effects of Fenchone, Sabinene and Protodioscin. To best of our knowledge, such type of studies facilitate the target fishing as well as making the roadmap in drug design and discovery process for identification of novel therapeutics.

Keywords: epigenetics, spices, phytochemicals, fenchone

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319 A Study on Awareness and Attitude of First-Year Medical Students on Epilepsy in University of Khartoum 2020-2021

Authors: Mohammed E. Ibrahim, Baraa A. Taha, Kamil M. A. Shabban

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Background: Epilepsy is a common but widely misunderstood illness. Consequently, patients with epilepsy suffer from considerable stigmatization in society. This social stigma and discrimination often cause more suffering for the patients than the disease itself. Since very few studies have explored the misperceptions about epilepsy among university students in Sudan, it is not possible to provide focused intervention aimed at eliminating this discrimination. Methods: A cross-sectional study was applied among the first-year medical students at the University of Khartoum between December (2020) and February (2021). A 29-item standardized questionnaire was self-administered by 198 students (out of 320) who agreed to participate in this study. Google form was the tool used to collect the data. The data were analyzed using the Statistical Package for Social Science software version 26. Result: Overall, the results indicate a negative trend in knowledge and attitude toward epilepsy. The vast majority of the respondents (84.8%) have read or heard about epilepsy, while 43.9% had seen someone with epilepsy. Only 7.5% of the participants reported that epilepsy is contagious, whereas 43.4% of them think that epilepsy is a psychological disorder. About 62.2% of students think head/birth trauma is a cause of epilepsy. On the other side, about 15.7% and 5.1% believed that evil spirits and punishment from god can also be a possible cause of epilepsy; we found these false beliefs are more common in participants from rural areas (p-value < 0.05). In regard to attitude, 19.7% of students thought that it is inappropriate for a patient with epilepsy to have a child. This attitude correlates with the mother’s education as the percentage is higher for those who have lower mother’s education (through secondary school education and below) (p < 0.05). The majority of Our participant knew that some people with epilepsy need life-long drug treatment; this belief was found to be more common in females than their counterparts(p < 0.05). . Finally, most of the respondents (93.9%) thought that a child with epilepsy Can be successful in a normal class. This belief is four-time as common in participants whose mothers have higher education (through university education and above) compared with corresponding respondents (p < 0.05). Conclusion: This study concludes that students' knowledge about epilepsy is limited and requires immediate intervention through educational campaigns to develop a well-informed and tolerant community.

Keywords: epilepsy, awareness, attitude, university students, Sudan

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318 Design and Development of Bioactive a-Hydroxy Carboxylate Group Modified MnFe₂O₄ Nanoparticle: Comparative Fluorescence Study, Magnetism and DNA Nuclease Activity

Authors: Indranil Chakraborty, Kalyan Mandal

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Three new α-hydroxy carboxylate group functionalized MnFe₂O₄ nanoparticles (NPs) have been developed to explore the microscopic origin of ligand modified fluorescence and magnetic properties of nearly monodispersed MnFe₂O₄ NPs. The surface functionalization has been carried out with three small organic ligands (tartrate, malate, and citrate) having different number of α-hydroxy carboxylate functional group along with steric effect. Detailed study unveils that α-hydroxy carboxylate moiety of the ligands plays key role to generate intrinsic fluorescence in functionalized MnFe₂O₄ NPs through the activation of ligand to metal charge transfer transitions, associated with ligand-Mn²⁺/Fe³⁺ interactions along with d-d transition corresponding to d-orbital energy level splitting of Fe³⁺ ions on NP surface. Further, MnFe₂O₄ NPs show a maximum 140.88% increase in coercivity and 97.95% decrease in magnetization compared to its bare one upon functionalization. The ligands that induce smallest crystal field splitting of d-orbital energy level of transition metal ions are found to result in strongest ferromagnetic activation of the NPs. Finally, our developed tartrate functionalized MnFe₂O₄ (T-MnFe₂O₄) NPs have been utilized for studying DNA binding interaction and nuclease activity for stimulating their beneficial activities toward diverse biomedical applications. The spectroscopic measurements indicate that T-MnFe₂O₄ NPs bind calf thymus DNA by intercalative mode. The ability of T-MnFe₂O₄ NPs to induce DNA cleavage was studied by gel electrophoresis technique where the complex is found to promote the cleavage of pBR322 plasmid DNA from the super coiled form I to linear coiled form II and nicked coiled form III with good efficiency. This may be taken into account for designing new biomolecular detection agents and anti-cancer drug which can open up a new door toward diverse non-invasive biomedical applications.

Keywords: MnFe₂O₄ nanoparticle, α-hydroxy carboxylic acid, comparative fluorescence, magnetism study, DNA interaction, nuclease activity

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317 The State of Research on Medicinal Plants in Morocco

Authors: Alami Ilyass, Loubna Kharchoufa, Elachouri Mostafa

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The two great realms of living diversity are cultural and biological. Today, both are being lost at an alarming rate. Of all the Earth’s biological diversity, plant kingdom is of high significance, and most essential to human welfare, in fact, medicinal plants are extensively exploited for countless purposes. Among these multiple uses, medicinal plants are the most important source of medicine for humankind healthcare and well being. In recent years there has been a great surge of public interest in the use of herbs and plants. Some scientists have viewed this phenomenon as a modern “herbal renaissance”. The importance of plants as medicines in developed and developing countries has recently been acknowledged by the United Nations (UN). However, to date fewer than 5% of the approximately 250,000 species of higher plants have been exhaustively studied for their potential pharmacological activity. A number of drugs from ethnobotanical leads have provided significant milestones in Western medicine. Despite this success, pharmacognosy research on Moroccan flora needs more studies aimed at the exploration of their therapeutic potential. A major weakness is the absence of strong funding agencies in the country, and a real national drug discovery program. Moreover, the lack of the coordination between different universities and research institutions leads, in most cases, to a waste of time, money and efforts of many researchers. In this work, we focus our attention on research into traditional indigenous medicinal plants in Morocco. Three parts constitute the head lines of this work: In the first one, we take up Moroccan biodiversity matter, the second part is devoted principally to the state of research into medicinal plants by Moroccan scholars and the last one is consecrated to the debate of factors which handicap the progress of research on phytomedicine in Morocco. The objectives of the present study are twofold: first, to highlight the state of the medicinal plants researches in Morocco. Second goal is to assess and correlate the levels of knowledge of the local flora to the research on medicinal plants to attempt to build capacity for research within Moroccan Scientific community at rate of developing country.

Keywords: Morocco, medicinal plants, ethnobotanical, pharmacognosy, phytomedicine

Procedia PDF Downloads 160
316 3D Interpenetrated Network Based on 1,3-Benzenedicarboxylate and 1,2-Bis(4-Pyridyl) Ethane

Authors: Laura Bravo-García, Gotzone Barandika, Begoña Bazán, M. Karmele Urtiaga, Luis M. Lezama, María I. Arriortua

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Solid coordination networks (SCNs) are materials consisting of metal ions or clusters that are linked by polyfunctional organic ligands and can be designed to form tridimensional frameworks. Their structural features, as for example high surface areas, thermal stability, and in other cases large cavities, have opened a wide range of applications in fields like drug delivery, host-guest chemistry, biomedical imaging, chemical sensing, heterogeneous catalysis and others referred to greenhouse gases storage or even separation. In this sense, the use of polycarboxylate anions and dipyridyl ligands is an effective strategy to produce extended structures with the needed characteristics for these applications. In this context, a novel compound, [Cu4(m-BDC)4(bpa)2DMF]•DMF has been obtained by microwave synthesis, where m-BDC is 1,3-benzenedicarboxylate and bpa 1,2-bis(4-pyridyl)ethane. The crystal structure can be described as a three dimensional framework formed by two equal, interpenetrated networks. Each network consists of two different CuII dimers. Dimer 1 have two coppers with a square pyramidal coordination, and dimer 2 have one with a square pyramidal coordination and other with octahedral one, the last dimer is unique in literature. Therefore, the combination of both type of dimers is unprecedented. Thus, benzenedicarboxylate ligands form sinusoidal chains between the same type of dimers, and also connect both chains forming these layers in the (100) plane. These layers are connected along the [100] direction through the bpa ligand, giving rise to a 3D network with 10 Å2 voids in average. However, the fact that there are two interpenetrated networks results in a significant reduction of the available volume. Structural analysis was carried out by means of single crystal X-ray diffraction and IR spectroscopy. Thermal and magnetic properties have been measured by means of thermogravimetry (TG), X-ray thermodiffractometry (TDX), and electron paramagnetic resonance (EPR). Additionally, CO2 and CH4 high pressure adsorption measurements have been carried out for this compound.

Keywords: gas adsorption, interpenetrated networks, magnetic measurements, solid coordination network (SCN), thermal stability

Procedia PDF Downloads 293
315 Enhancement in Antimicrobial and Antioxidant Activity of Cuminum cyminum L. through Niosome Nanocarries

Authors: Fatemeh Haghiralsadat, Mohadese Hashemi, Elham Akhoundi Kharanaghi, Mojgan Yazdani, Mahboobe Sharafodini, Omid Javani

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Niosomes are colloidal particles formed from the self-assembly of non-ionic surfactants in aqueous medium resulting in closed bilayer structures. As a consequence of this hydrophilic and hydrophobic structure, niosomes have the capacity to entrap compounds of different solubilities. Niosomes are promising vehicle for drug delivery which protect sensitive drugs and improve the therapeutic index of drugs by restricting their action to target cells. Essential oils are complex mixtures of volatile compounds such as terpenoids, phenol-derived aromatic components that have been used for many biological properties including bactericidal, fungicidal, insecticidal, antioxidant, anti-tyrosinase and other medicinal properties. Encapsulation of essential oils in niosomes can be an attractive method to overcome their limitation such as volatility, easily decomposition by heat, humidity, light, or oxygen. Cuminum cyminum L. (Cumin) is an aromatic plant included in the Apiaceae family and is used to flavor foods, added to fragrances, and for medical preparations which is indigenous to Egypt, the Mediterranean region, Iran and India. The major components of the Cumin oil were reported as cuminaldehyde, γ -terpinene, β-pinene, p-cymene, p-mentha-1, 3-dien-7-al, and p-mentha-1, 4-dien-7-al which provide the antimicrobial and antioxidant activity. The aim of this work was to formulate Cumin essential oil-loaded niosomes to improve water solubility of natural product and evaluate its physico-chemical features and stability. Cumin oil was obtained through steam distillation using a clevenger-type apparatus and GC/MS was applied to identify the main components of the essential oil. Niosomes were prepared by using thin film hydration method and nanoparticles were characterized for particle size, dispersity index, zeta potential, encapsulation efficiency, in vitro release, and morphology.

Keywords: Cuminum cyminum L., Cumin, niosome, essential oil, encapsulation

Procedia PDF Downloads 492
314 Dipeptide Functionalized Nanoporous Anodic Aluminium Oxide Membrane for Capturing Small Molecules

Authors: Abdul Mutalib Md Jani, Abdul Hadi Mahmud, Mohd Tajuddin Mohd Ali

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The rapid growth of interest in surface modification of nanostructures materials that exhibit improved structural and functional properties is attracting more researchers. The unique properties of highly ordered nanoporous anodic aluminium oxide (NAAO) membrane have been proposed as a platform for biosensing applications. They exhibit excellent physical and chemical properties with high porosity, high surface area, tunable pore sizes and excellent chemical resistance. In this study, NAAO was functionalized with 3-aminopropyltriethoxysilane (APTES) to prepared silane-modified NAAO. Amine functional groups are formed on the surface of NAAO during silanization and were characterized using Fourier Transform Infrared spectroscopy (FTIR). The synthesis of multi segment of peptide on NAAO surfaces can be realized by changing the surface chemistry of the NAAO membrane via click chemistry. By click reactions, utilizing alkyne terminated with amino group, various peptides tagged on NAAO can be envisioned from chiral natural or unnatural amino acids using standard coupling methods (HOBt, EDCI and HBTU). This strategy seemly versatile since coupling strategy of dipeptide with another amino acids, leading to tripeptide, tetrapeptide or pentapeptide, can be synthesized without purification. When an appropriate terminus is selected, multiple segments of amino acids can be successfully synthesized on the surfaces. The immobilized NAAO should be easily separated from the reaction medium by conventional filtration, thus avoiding complicated purification methods. Herein, we proposed to synthesize multi fragment peptide as a model for capturing and attaching various small biomolecules on NAAO surfaces and can be also applied as biosensing device, drug delivery systems and biocatalyst.

Keywords: nanoporous anodic aluminium oxide, silanization, peptide synthesise, click chemistry

Procedia PDF Downloads 254
313 In vitro Modeling of Aniridia-Related Keratopathy by the Use of Crispr/Cas9 on Limbal Epithelial Cells and Rescue

Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

Procedia PDF Downloads 178
312 A Next Generation Multi-Scale Modeling Theatre for in silico Oncology

Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal

Abstract:

Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.

Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling

Procedia PDF Downloads 181
311 D-Epi App: Mobile Application to Control Sodium Valproat Administration in Children with Idiopatic Epilepsy in Indonesia

Authors: Nyimas Annissa Mutiara Andini

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There are 325,000 children younger than age 15 in the U.S. have epilepsy. In Indonesia, 40% of 3,5 millions cases of epilepsy happens in children. The most common type of epilepsy, which affects 6 out of 10 people with the disorder, is called idiopathic epilepsy and which has no identifiable cause. One of the most commonly used medications in the treatment of this childhood epilepsy is sodium valproate. Administration of sodium valproat in children has a problem to fail. Nearly 60% of pediatric patients known were mildly, moderately, or severely non-adherent with therapy during the first six months of treatment. Many parents or caregiver took far less medication than prescribed, and the treatment-adherence pattern for the majority of patients was established during the first month of treatment. 42% of the patients were almost always given their medications as prescribed but 13% had very poor adherence even in the early weeks and months of treatment. About 7% of patients initially gave the medication correctly 90% of the time, but adherence dropped to around 20% within six months of starting treatment. Over the six months of observation, the total missing of administration is about four out of 14 doses in any given week. This fail can cause the epilepsy to relapse. Whereas, current reported epilepsy disorder were significantly more likely than those never diagnosed to experience depression (8% vs 2%), anxiety (17% vs 3%), attention-deficit/hyperactivity disorder (23% vs 6%), developmental delay (51% vs 3%), autism/autism spectrum disorder (16% vs 1%), and headaches (14% vs 5%) (all P< 0.05). They had a greater risk of limitation in the ability to do things (relative risk: 9.22; 95% CI: 7.56–11.24), repeating a school grade (relative risk: 2.59; CI: 1.52–4.40), and potentially having unmet medical and mental health needs. In the other side, technology can help to make our life easier. One of the technology, that we can use is a mobile application. A mobile app is a software program we can download and access directly using our phone. Indonesians are highly mobile centric. They use, on average, 6.7 applications over a 30 day period. This paper is aimed to describe an application that could help to control a sodium valproat administration in children; we call it as D-Epi app. D-Epi app is a downloadable application that can help parents or caregiver alert by a timer-related application to warn whether it is the time to administer the sodium valproat. It works not only as a standard alarm, but also inform important information about the drug and emergency stuffs to do to children with epilepsy. This application could help parents and caregiver to take care a child with epilepsy in Indonesia.

Keywords: application, children, D-Epi, epilepsy

Procedia PDF Downloads 254