Search results for: keratinocyte cells
731 Theoretical Analysis of Mechanical Vibration for Offshore Platform Structures
Authors: Saeed Asiri, Yousuf Z. AL-Zahrani
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A new class of support structures, called periodic structures, is introduced in this paper as a viable means for isolating the vibration transmitted from the sea waves to offshore platform structures through its legs. A passive approach to reduce transmitted vibration generated by waves is presented. The approach utilizes the property of periodic structural components that creates stop and pass bands. The stop band regions can be tailored to correspond to regions of the frequency spectra that contain harmonics of the wave frequency, attenuating the response in those regions. A periodic structural component is comprised of a repeating array of cells, which are themselves an assembly of elements. The elements may have differing material properties as well as geometric variations. For the purpose of this research, only geometric and material variations are considered and each cell is assumed to be identical. A periodic leg is designed in order to reduce transmitted vibration of sea waves. The effectiveness of the periodicity on the vibration levels of platform will be demonstrated theoretically. The theory governing the operation of this class of periodic structures is introduced using the transfer matrix method. The unique filtering characteristics of periodic structures are demonstrated as functions of their design parameters for structures with geometrical and material discontinuities; and determine the propagation factor by using the spectral finite element analysis and the effectiveness of design on the leg structure by changing the ratio of step length and area interface between the materials is demonstrated in order to find the propagation factor and frequency response.Keywords: vibrations, periodic structures, offshore, platforms, transfer matrix method
Procedia PDF Downloads 290730 Influence of BaTiO₃ on the Biological Behaviour of Hydroxyapatite: Collagen Composites
Authors: Cristina Busuioc, Georgeta Voicu, Sorin-Ion Jinga
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The human bone presents in its dry form piezoelectric properties, which means that a mechanical stress results in electric polarization and an applied electric field causes strain. The immediate consequence was the revealing of piezoelectricity role in bone remodelling, as well as the integration of ceramic materials with piezoelectric behaviour in the composition of unitary or composite biomaterials. Thus, we prepared hydroxyapatite - collagen hybrid materials with barium titanate addition in order to achieve a better osseointegration. Barium titanate powder synthesized by a combined sol-gel-hydrothermal method, commercial hydroxyapatite and laboratory extracted collagen gel were employed as starting materials. Before the composites, fabrication, the powder with piezoelectric features was characterized in detail from the compositional, structural, morphological and electrical point of view. The next step was to elucidate the influence of barium titanate presence especially on the biological properties of the final materials. The biocompatibility of the hybrid supports without or with piezoelectric addition was investigated on mouse osteoblast cells through LDH cytotoxicity assay, LIVE/DEAD cell viability assay, and MTT cell proliferation assay. All results indicated that the analysed materials do not exert cytotoxic effects and present the ability to sustain cell survival and to promote their proliferation. In conclusion, barium titanate nanoparticles exhibit a good biocompatibility and osteoinductive properties, while the derived composite materials based on hydroxyapatite as oxide phase and collagen as polymeric phase can be successfully used for tissue engineering applications.Keywords: barium titanate, hybrid composites, piezoelectricity, tissue engineering
Procedia PDF Downloads 324729 Modifying the Electrical Properties of Liquid Crystal Cells by Including TiO₂ Nanoparticles on a Substrate
Authors: V. Marzal, J. C. Torres, B. Garcia-Camara, Manuel Cano-Garcia, Xabier Quintana, I. Perez Garcilopez, J. M. Sanchez-Pena
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At the present time, the use of nanostructures in complex media, like liquid crystals, is widely extended to manipulate their properties, either electrical or optical. In addition, these media can also be used to control the optical properties of the nanoparticles, for instance when they are resonant. In this work, the change on electrical properties of a liquid crystal cell by adding TiO₂ nanoparticles on one of the alignment layers has been analyzed. These nanoparticles, with a diameter of 100 nm and spherical shape, were deposited in one of the substrates (ITO + polyimide) by spin-coating in order to produce a homogeneous layer. These substrates were checked using an optical microscope (objective x100) to avoid potential agglomerates. The liquid crystal cell is then fabricated, using one of these substrates and another without nanoparticles, and filled with E7. The study of the electrical response was done through impedance measurements in a long range of frequencies (3 Hz- 6 MHz) and at ambient temperature. Different nanoparticle concentrations were considered, as well as pure E7 and an empty cell for comparison purposes. Results about the effective dielectric permittivity and conductivity are presented along with models of equivalent electric circuits and its physical interpretation. As a summary, it has been observed the clear influence of the presence of the nanoparticles, strongly modifying the electric response of the device. In particular, a variation of both the effective permittivity and the conductivity of the device have been observed. This result requires a deep analysis of the effect of these nanoparticles on the trapping of free ions in the device, allowing a controlled manipulation and frequency tuning of the electrical response of these devices.Keywords: alignment layer, electrical behavior, liquid crystal, TiO₂ nanoparticles
Procedia PDF Downloads 214728 Clinical Prediction Score for Ruptured Appendicitis In ED
Authors: Thidathit Prachanukool, Chaiyaporn Yuksen, Welawat Tienpratarn, Sorravit Savatmongkorngul, Panvilai Tangkulpanich, Chetsadakon Jenpanitpong, Yuranan Phootothum, Malivan Phontabtim, Promphet Nuanprom
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Background: Ruptured appendicitis has a high morbidity and mortality and requires immediate surgery. The Alvarado Score is used as a tool to predict the risk of acute appendicitis, but there is no such score for predicting rupture. This study aimed to developed the prediction score to determine the likelihood of ruptured appendicitis in an Asian population. Methods: This study was diagnostic, retrospectively cross-sectional and exploratory model at the Emergency Medicine Department in Ramathibodi Hospital between March 2016 and March 2018. The inclusion criteria were age >15 years and an available pathology report after appendectomy. Clinical factors included gender, age>60 years, right lower quadrant pain, migratory pain, nausea and/or vomiting, diarrhea, anorexia, fever>37.3°C, rebound tenderness, guarding, white blood cell count, polymorphonuclear white blood cells (PMN)>75%, and the pain duration before presentation. The predictive model and prediction score for ruptured appendicitis was developed by multivariable logistic regression analysis. Result: During the study period, 480 patients met the inclusion criteria; of these, 77 (16%) had ruptured appendicitis. Five independent factors were predictive of rupture, age>60 years, fever>37.3°C, guarding, PMN>75%, and duration of pain>24 hours to presentation. A score > 6 increased the likelihood ratio of ruptured appendicitis by 3.88 times. Conclusion: Using the Ramathibodi Welawat Ruptured Appendicitis Score. (RAMA WeRA Score) developed in this study, a score of > 6 was associated with ruptured appendicitis.Keywords: predictive model, risk score, ruptured appendicitis, emergency room
Procedia PDF Downloads 166727 Protective Effect of Saponin Extract from the Root of Garcinia kola (Bitter Kola) against Paracetamol-Induced Hepatotoxicity in Albino Rats
Authors: Alli Smith Yemisi Rufina, Adanlawo Isaac Gbadura
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Liver disorders are one of the major problems of the world. Despite its frequent occurrence, high morbidity, and high mortality, its medical management is currently inadequate. This study was designed to evaluate the Hepatoprotective effect of saponin extract of the root of Garcinia kola on the integrity of the liver of paracetamol induced Wistar albino rats. Twenty-five male adult Wistar albino rats were divided into five (5) groups. Group I, was the Control group that received distilled water only, group II was the negative control that received 2 g/kg of paracetamol on the 13th day, and group III, IV, and V were pre-treated with 100, 200 and 400 mg/kg of the saponin extract before inducing the liver damage on the 13th day with 2 g/kg of paracetamol. Twenty-four hours after administration, the rats were sacrificed, and blood samples were collected. The serum Alanine Transaminase (ALT), Aspartate Transaminase (AST), Alkaline Phosphatase (ALP) activities, Bilirubin and Conjugated Bilirubin, Glucose and Protein concentrations were evaluated. The liver was fixed immediately in Formalin and was processed and stained with Haematoxylin and Eosin (H&E). Administration of saponin extract from the root of Garcinia kola significantly decreased paracetamol induced elevated enzymes in the test group. Also, histological observations showed that saponin extract of the root of Garcinia kola exhibited a significant liver protection against the toxicant as evident by the cells trying to return to normal. Saponin extract from the root of Garcinia kola indicated a protection of the structural integrity of the hepatocytic cell membrane and regeneration of the damaged liver.Keywords: hepatoprotective, liver damage, Garcinia kola, saponin, paracetamol
Procedia PDF Downloads 261726 Appearance of Ciguatoxin Fish in Atlantic Europe Waters
Authors: J. Bravo, F. Cabrera Suárez, B. Vega, L. Román, M. Martel, F. Acosta
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Ciguatera fish poisoning (CFP) is the most common non-bacterial intoxication in the world caused by ingestion of fish with bio-accumulated ciguatoxins (CTXs). It is typical in tropical and subtropical areas, mainly affecting the Caribbean Sea, Polynesia and other areas in the Pacific and Indian Oceans. Interest in Europe by the CFP is increasing in recent years as more and more cases in European hospitals are appearing, usually by people who have consumed ciguatoxin imported fish or have travelled to areas of risk for this poisoning. Since 2004 a series of poisonings raised the question of a possible occurrence of ciguatoxin in Europe, especially in the area of Macaronesia in the East Atlantic temperate zone. Furthermore, some studies have identified the presence of Gambierdiscus spp. in waters surrounding the Canary Islands and Madeira, a toxic dinoflagellate related to this poisoning. The toxin accumulates and concentrates through the food chain and affects to the end of the chain, the human consumer. Fish were collected from the Canary Islands waters and the toxin has been extracted and purified by using acetone and liquid/liquid partition in order to eliminate the excess of fatty acids that may interfere with the detection of the toxin. The fish extracts were inoculated in Neuroblastoma (neuro-2a) cells. After 24-h cell viability was used as an endpoint for cytotoxic effects measurement. Since 2011 our laboratory is collecting data for species such Seriola spp., Epinephelus spp., Makaira spp., Pomatomus spp., Xiphias spp., and Acantocybium spp., from all islands and including the sports fishing and professional activities, we obtained a 8% of fish that have ciguatoxin in their muscle. With these results, we conclude that the island where fishing and fish size affects the probability of catching a fish with the ciguatoxin.Keywords: Canary Islands, ciguatera fish poisoning, ciguatoxin, Europe
Procedia PDF Downloads 349725 The Effects of Ellagic Acid on Rat Liver Induced Tobacco Smoke
Authors: Nalan Kaya, Elif Erdem, Mehmet Ali Kisacam, Gonca Ozan, Enver Ozan
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Tobacco smokers continuously inhale thousands of carcinogens and free radicals. It is estimated that about 1017 oxidant molecules are present in each puff of tobacco smoke. It is known that smoking has adverse effects on the structure and functions of the liver. Ellagic acid (EA) has antioxidant, antiapoptotic, anticarcinogenic, antibacterial and antiinflammatory effects. The aim of our study was to investigate the possible protective effect of ellagic acid against tobacco smoke-mediated oxidative stress in the rat liver. Twenty-four male adult (8 weeks old) Spraque-Dawley rats were divided randomly into 4 equal groups: group I (control), group II (tobacco smoke), group III (tobacco smoke + corn oil) and group IV (tobacco smoke + ellagic acid). The rats in group II, III and IV, were exposed to tobacco smoke 1 hour twice a day for 12 weeks. In addition to tobacco smoke exposure, 12 mg/kg ellagic acid (dissolved in corn oil), was applied to the rats in group IV by oral gavage. An equal amount of corn oil used in solving ellagic acid was applied to the rats by oral gavage in group III. At the end of the experimental period, rats were decapitated, and liver tissues were removed. Histological and biochemical analyzes were performed. Sinusoidal dilatation, inflammatory cell infiltration in portal area, increased Kuppfer cells were examined in tobacco smoke group and tobacco smoke+ corn oil groups. The results, observed in tobacco smoke and tobacco smoke+corn oil groups, were found significantly decreased in tobacco smoke+EA group. Group-II and group-III MDA levels were significantly higher, and GSH activities were not different than group-I. Compared to group-II, group-IV MDA level was decreased, and GSH activities was increased significantly. The results indicate that ellagic acid could protect the liver tissue from the tobacco smoke harmful effects.Keywords: ellagic acid, liver, rat, tobacco smoke
Procedia PDF Downloads 300724 Role of ABC Transporters in Non-Target Site Herbicide Resistance in Black Grass (Alopecurus myosuroides)
Authors: Alina Goldberg Cavalleri, Sara Franco Ortega, Nawaporn Onkokesung, Richard Dale, Melissa Brazier-Hicks, Robert Edwards
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Non-target site based resistance (NTSR) to herbicides in weeds is a polygenic trait associated with the upregulation of proteins involved in xenobiotic detoxification and translocation we have termed the xenome. Among the xenome proteins, ABC transporters play a key role in enhancing herbicide metabolism by effluxing conjugated xenobiotics from the cytoplasm into the vacuole. The importance of ABC transporters is emphasized by the fact that they often contribute to multidrug resistance in human cells and antibiotic resistance in bacteria. They also play a key role in insecticide resistance in major vectors of human diseases and crop pests. By surveying available databases, transcripts encoding ABCs have been identified as being enhanced in populations exhibiting NTSR in several weed species. Based on a transcriptomics data in black grass (Alopecurus myosuroides, Am), we have identified three proteins from the ABC-C subfamily that are upregulated in NTSR populations. ABC-C transporters are poorly characterized proteins in plants, but in Arabidopsis localize to the vacuolar membrane and have functional roles in transporting glutathionylated (GSH)-xenobiotic conjugates. We found that the up-regulation of AmABCs strongly correlates with the up-regulation of a glutathione transferase termed AmGSTU2, which can conjugate GSH to herbicides. The expression profile of the ABC transcripts was profiled in populations of black grass showing different degree of resistance to herbicides. This, together with a phylogenetic analysis, revealed that AmABCs cluster in different groups which might indicate different substrate and roles in the herbicide resistance phenotype in the different populationsKeywords: black grass, herbicide, resistance, transporters
Procedia PDF Downloads 158723 Efficacy of Ethanolic Extract of Aerva javanica Aerial Parts in the Amelioration of CCl4-Induced Hepatotoxicity and Oxidative Damage in Rats
Authors: Mohammad K. Parvez, Ahmed H. Arbab, Mohammed S. Al-Dosari, Adnan J. Al-Rehaily
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We investigated ex vivo and in vivo antioxidative and hepatoprotective effect of Aerva javanica. Total ethanol extract of A. javanica aerial parts was prepared, and tested on DCFH-toxicated HepG2 cell in CCl4-injured Wistar rats. MTT-assay was used to determine cell viability, and serum biochemical markers of liver injury as well as histopathology were performed. In vitro DPPH and β-carotene free-radical scavenging assay and phytochemical screening of the extract was done. Furthermore, A. javanica total extract was standardized and validated by HPTLC method. While DCFH-injured cells were recovered to about 56.7% by 100 microg/ml of the extract, a 200 microg/ml dose resulted in hepatocytes recovery by about 90.2%. Oral administration of the extract (100 and 200 mg/kg.bw/day) significantly normalized the serum SGOT, SGPT, GGT, ALP, bilirubin, cholesterol, HDL, LDL, VLDL, TG and MDA levels, including tissue NP-SH and TP in CCl4-injured rats. In addition, the histopathology of dissected liver also revealed that A. javanica cured the tissue lesion compared to reference drug, Silymarin. In vitro assays revealed strong free-radical scavenging ability of the extract and presence of alkaloids, flavonoids, tannins, sterols and saponins where Rutin, a well-known antioxidant flavonoid was identified. Our finding therefore, suggests the therapeutic potential of A. javanica in various liver diseases. However, isolation of the active principles, their mechanism of action and other therapeutic contribution remain to be addressed.Keywords: Aerva javanica, antioxidant, hepatoprotection, rutin
Procedia PDF Downloads 296722 Effect of Different Arsenic Treatments on Root Growth of Sunflower Seedlings in Rhizobox Experiment
Authors: Szilvia Várallyay, Béla Kovács, Éva Bódi, Farzeneh Garousi, Szilvia Veres
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Arsenic (As) is a naturally occurring substance that can be present in soil, water and air. Vegetables, fruits, and other plants that grow in contaminated soils which are able to accumulate arsenic. Arsenic when presents in plant cells, has various negative physiological effects and when presents in soil will be inorgaic form, namely arsenite (As(III)) and arsenate (As(V)). These two forms of arsenic disrupt plant metabolism by inhibiting its growth and these arsenic species has negative effect on nutrient uptake. A rhizobox experiment was conducted to investigate the effect of arsenite and arsenate on root growth of sunflower seedlings. Sunflower plants were grown in climatic room under irradiance of 300 µmol m-2 s-1, 16-h day and 8-h night photoperiod, day/night temperature of 25/20°C and relative humidity of 65-75%. We applied arsenic in form of arsenite (NaAsO2) and arsenate (KH2AsO4), respectively. The applied arsenic treatments was 0, 10, 30, 90 mg.kg-1. After disinfection, seeds were germinated between moist filter papers. Seedlings with 2-3 cm coleoptils were placed into rhizoboxes. In the rhizoboxes the growing and daily growing rhythm of roots of sunflower can be followed up, moreover possible phytotoxic symptoms of roots resulting from increasing arsenic can be seen. Weights of rhizoboxes were measured daily and also evaporated water added each day. The lengths of roots were measured daily until seedlings roots get at the end of the rhizoboxes. Negative correlation was observed between the higher concentration of arsenic in the soil and the growth of sunflower seedlings roots. The effect of arsenic toxicity was more considerable in 90 mg.kg-1 arsenic treatment than lower concentration. The same arsenite concentration causes slower growth in case of sunflower plant than the same arsenate concentration produced.Keywords: arsenic, rhizobox experiment, sunflower, root growth
Procedia PDF Downloads 419721 Characterization and Degradation of 3D Printed Polycaprolactone-Freeze Dried Bone Matrix Constructs for Use in Critical Sized Bone Defects
Authors: Samantha Meyr, Eman Mirdamadi, Martha Wang, Tao Lowe, Ryan Smith, Quinn Burke
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Critical-sized bone defects (CSD) treatment options remain a major clinical orthopedic challenge. They are uniquely contoured diseased or damaged bones and can be defined as those that will not heal spontaneously and require surgical intervention. Autografts are the current gold standard CSD treatment, which are histocompatible and provoke a minimal immunogenic response; however, they can cause donor site morbidity and will not suffice for the size required for replacement. As an alternative to traditional surgical methods, bone tissue engineering will be implemented via 3D printing methods. A freeze-dried bone matrix (FDBM) is a type of graft material available but will only function as desired when in the presence of bone growth factors. Polycaprolactone (PCL) is a known biodegradable material with good biocompatibility that has been proven manageable in 3D printing as a medical device. A 3D-extrusion printing strategy is introduced to print these materials into scaffolds for bone grafting purposes, which could be more accessible and rapid than the current standard. Mechanical, thermal, cytotoxic, and physical properties were investigated throughout a degradation period of 6 months using fibroblasts and dental pulp stem cells. PCL-FDBM scaffolds were successfully printed with high print fidelity in their respective pore sizes and allograft content. Additionally, we have created a method for evaluating PCL using differential scanning calorimetry (DSC) and have evaluated PCL degradation over roughly 6 months.Keywords: 3D printing, bone tissue engineering, cytotoxicity, degradation, scaffolds
Procedia PDF Downloads 106720 Study on the Impact of Power Fluctuation, Hydrogen Utilization, and Fuel Cell Stack Orientation on the Performance Sensitivity of PEM Fuel Cell
Authors: Majid Ali, Xinfang Jin, Victor Eniola, Henning Hoene
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The performance of proton exchange membrane (PEM) fuel cells is sensitive to several factors, including power fluctuations, hydrogen utilization, and the quality orientation of the fuel cell stack. In this study, we investigate the impact of these factors on the performance of a PEM fuel cell. We start by analyzing the power fluctuations that are typical in renewable energy systems and their effects on the 50 Watt fuel cell's performance. Next, we examine the hydrogen utilization rate (0-1000 mL/min) and its impact on the cell's efficiency and durability. Finally, we investigate the quality orientation (three different positions) of the fuel cell stack, which can significantly affect the cell's lifetime and overall performance. The basis of our analysis is the utilization of experimental results, which have been further validated by comparing them with simulations and manufacturer results. Our results indicate that power fluctuations can cause significant variations in the fuel cell's voltage and current, leading to a reduction in its performance. Moreover, we show that increasing the hydrogen utilization rate beyond a certain threshold can lead to a decrease in the fuel cell's efficiency. Finally, our analysis demonstrates that the orientation of the fuel cell stack can affect its performance and lifetime due to non-uniform distribution of reactants and products. In summary, our study highlights the importance of considering power fluctuations, hydrogen utilization, and quality orientation in designing and optimizing PEM fuel cell systems. The findings of this study can be useful for researchers and engineers working on the development of fuel cell systems for various applications, including transportation, stationary power generation, and portable devices.Keywords: fuel cell, proton exchange membrane, renewable energy, power fluctuation, experimental
Procedia PDF Downloads 135719 Polycystic Ovary Syndrome: Cervical Cytology Features and Its Association with Endometrial Cancer
Authors: Faezah Shekh Abdullah, Mohd. Azizuddin Mohd. Yussof, Komathy Thiagarajan, Hasnoorina Husin, Noor Azreena Abd Aziz
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Polycystic ovary syndrome has been associated with multiple disorders such as endocrine disorder, metabolic syndrome, infertility, and endometrial cancer. Women with polycystic ovary syndrome (PCOS) are anticipated to develop three times more chances for endometrial cancer than women without PCOS. This study, therefore, was conducted to determine the association between polycystic ovary syndrome and endometrial cancer and to determine the cervical cytology features of PCOS. Patients attending the Subfertility Clinic of the National Population and Family Development Board were recruited and examined physically by medical practitioners. They were categorized into two groups; i) the PCOS group if they met Rotterdam Criteria 2004 and ii) the control group if they did not meet Rotterdam Criteria 2004. Cervical sampling was done on all patients via the Liquid-Based Cytology (LBC) method in the pre-and post-subfertility treatment. A total of 167 patients participated in the study, of which 79 belonged to the PCOS group and 88 to the control group. The findings showed no cervical and endometrial cancer cases in both groups. The Liquid-Based Cytology results in the PCOS group displayed more cases with cellular changes, i.e., benign inflammation, atrophic smear and Candida sp. infection. To conclude, no association was found between polycystic ovary syndrome and endometrial cancer. A more holistic study with a higher number of participants can further determine the association between endometrial cancer and PCOS. Furthermore, a longer duration between LBC pre- and post-subfertility treatment should be implied to observe changes in the cervical cells.Keywords: endometrial cancer, liquid-based cytology, PCOS, polycystic ovary syndrome
Procedia PDF Downloads 144718 Immune Response and Histological Alteration in the Crab Carcinus aestuarii, Due to Silver Nanoparticles
Authors: Ines Kovacic, Dijana Pavicic-Hamer, Petra Buric, Maja Levak Zorinc, Daniel M. Lyons
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Silver nanoparticles (AgNPs), owing to their unique physical and chemical properties, have become one of the most widely used nanoparticles in consumer products. Despite the increased use of AgNPs in science and industry over the past twenty years, only relatively recently has concern been raised over their entering brackish and marine environments. However, data on their potential impact on marine organisms, especially invertebrates are very limited. This study aimed to examine the effects of 60 nm AgNPs (10, 100, 500 and 1000 µg/l) and silver ions (100, 1000 µg/l) on the Mediterranean green crab Carcinus aestuarii Nardo, 1847. The crab mortality was assessed during seven days of exposure. After the exposure, total haemocytes (THC) and differential haemocytes number (DHC) were counted (immune response), in addition to histological examination of gills stained with haematoxylin and eosin. The effect of AgNPs and silver ions resulted in a dose dependent mortality and destruction of gills epithelium with haemocytes infiltration in the gills lacuna. Total haemocyte count was greater with increasing concentration of AgNPs, at concentrations from 10 to 500 µg/l. Hyalinocytes were the most common immunological cells noted in the crab hemolymph, while granulocytes and semigranulocytes were suppressed with increasing concentration of AgNPs (500 and 1000 µg/l). Thus, as crabs are filter feeders, they are susceptible to uptake of AgNPs by direct accumulation in gills mucus or indirectly via circulation of haemocytes in their open vascular system. Results of this study on crabs add to knowledge of the effects of AgNPs in the marine environment.Keywords: crab, immune response, histological alteration, silver nanoparticles
Procedia PDF Downloads 155717 Double-Spear 1-H2-1 Oncolytic-Immunotherapy for Refractory and Relapsing High-Risk Human Neuroblastoma and Glioma
Authors: Lian Zeng
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Double-Spear 1-H2-1 (DS1-H2-1) is an oncolytic virus and an innovative biological drug candidate. The chemical composition of the drug product is a live attenuated West Nile virus (WNV) containing the human T cell costimulator (CD86) gene. After intratumoral injection, the virus can rapidly self-replicate in the injected site and lyse/kill the tumor by repeated infection among tumor cells. We also established xenograft tumor models in mice to evaluate the drug candidate's efficacy on those tumors. The results from preclinical studies on transplanted tumors in immunodeficient mice showed that DS1-H2-1 had significant oncolytic effects on human-origin cancers: it completely (100%) shrieked human glioma; limited human neuroblastoma growth reached as high as 95% growth inhibition rate (%TGITW). The safety data of preclinical animal experiments confirmed that DS1-H2-1 is safe as a biological drug for clinical use. In the preclinical drug efficacy experiment, virus-drug administration with different doses did not show abnormal signs and disease symptoms in more than 300 tested mice, and no side effects or death occurred through various administration routes. Intravenous administration did not cause acute infectious disease or other side effects. However, the replication capacity of the virus in tumor tissue via intravenous administration is only 1% of that of direct intratumoral administration. The direct intratumoral administration of DS1-H2-1 had a higher rate of viral replication. Therefore, choosing direct intratumoral injection can ensure both efficacy and safety.Keywords: oncolytic virus, WNV-CD86, immunotherapy drugs, glioma, neuroblastoma
Procedia PDF Downloads 135716 A Review on the Hydrologic and Hydraulic Performances in Low Impact Development-Best Management Practices Treatment Train
Authors: Fatin Khalida Abdul Khadir, Husna Takaijudin
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Bioretention system is one of the alternatives to approach the conventional stormwater management, low impact development (LID) strategy for best management practices (BMPs). Incorporating both filtration and infiltration, initial research on bioretention systems has shown that this practice extensively decreases runoff volumes and peak flows. The LID-BMP treatment train is one of the latest LID-BMPs for stormwater treatments in urbanized watersheds. The treatment train is developed to overcome the drawbacks that arise from conventional LID-BMPs and aims to enhance the performance of the existing practices. In addition, it is also used to improve treatments in both water quality and water quantity controls as well as maintaining the natural hydrology of an area despite the current massive developments. The objective of this paper is to review the effectiveness of the conventional LID-BMPS on hydrologic and hydraulic performances through column studies in different configurations. The previous studies on the applications of LID-BMP treatment train that were developed to overcome the drawbacks of conventional LID-BMPs are reviewed and use as the guidelines for implementing this system in Universiti Teknologi Petronas (UTP) and elsewhere. The reviews on the analysis conducted for hydrologic and hydraulic performances using the artificial neural network (ANN) model are done in order to be utilized in this study. In this study, the role of the LID-BMP treatment train is tested by arranging bioretention cells in series in order to be implemented for controlling floods that occurred currently and in the future when the construction of the new buildings in UTP completed. A summary of the research findings on the performances of the system is provided which includes the proposed modifications on the designs.Keywords: bioretention system, LID-BMP treatment train, hydrological and hydraulic performance, ANN analysis
Procedia PDF Downloads 119715 Gethuk Marillo: The New Product Development of Anti-Cancer Snacks Utilizing Xanthones and Anthocyanin in Mangosteen Pericarp and Tamarillo Fruit
Authors: Desi Meriyanti, Delina Puspa Rosana Firdaus, Ristia Rinati
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Nowadays, the presence of free radicals become a big concern due to its negative impact to the body, which can triggers the formation of degenerative diseases such as cancer, heart disease cardiovascular, diabetic mellitus and others. Free radical oxidation can be prevented by the presence of antioxidants. Naturally, the human body produces its own antioxidants. Because of the free radicals exposure are so intense, especially from the environment, it is necessary to supply antioxidants needed from outside, through the consumption of functional foods with high antioxidant content. Gethuk is one of the traditional snacks in Indonesia. Gethuk is made from cassava with minimal processing such as boiling, destructing, and forming. Gethuk is classified as a familiar snack in the community, so it has a potential for developing, especially into a functional food. The low content of antioxidants in gethuk can be overcome with the development of a product called Gethuk Marillo. Gethuk Marillo is gethuk with the addition of natural antioxidants from mangosteen pericarp extract which has a high content of xanthones, these compounds are classified into flavonoids and act as antioxidants in the body. Gethuk Marillo served along with tamarillo fruit sauce which is also high in antioxidants such as anthocyanin. The combination between 300 grams gethuk Marillo and sauce contain flavonoid about 31% of human antioxidant needs per day. Gethuk Marillo called as a functional food because of high flavonoids content which can prevent degenerative diseases namely cancer, as many studies that the xanthone and anthocyanins compounds can effectively prevent the formation of cancer cells in human body.Keywords: Gethuk marillo, xanthones, anthocyanin, high antioxidants, anti-cancer
Procedia PDF Downloads 656714 Malignant Idiopathic Intracranial Hypertension Revealed a Hidden Primary Spinal Leptomeningeal Medulloblastoma
Authors: Naim Izet Kajtazi
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Context: Frequently, the cause of raised intracranial pressure remains unresolved and rarely is related to spinal tumors, moreover less to spinal medulloblastoma without primary brain focus. Process: An 18-year-old woman had a 3-month history of headaches and impaired vision. Neurological examination revealed bilateral sixth cranial nerve palsies with bilateral papilloedema of grade III. No focal brain or spine lesion was found on imaging. Consecutive lumbar punctures showed high opening pressure and subsequent increasing protein level. The meningeal biopsy was negative. At one point, she developed an increasing headache, vomiting and back pain. Spine MRI showed diffuse nodular leptomeningeal enhancement with the largest nodule at T6–T7. Malignant cells were detected in cerebrospinal fluid. She underwent laminectomy with excisional biopsy, and pathology showed medulloblastoma WHO grade IV. Outcome: She was treated with chemotherapy and craniospinal irradiation and made a good recovery. Relevance: Primary spinal leptomeningeal medulloblastoma is extremely rare, especially without primary brain focus, but may cause increased intracranial pressure, even in the early microscopic phases, and it should be considered in the differential diagnosis if conventional and aggressive treatment of idiopathic intracranial hypertension fails. We assume that arachnoiditis from tumor seeding caused increased intracranial pressure. Appropriate neurosurgical intervention and surgical biopsy are mandated if a suspicious lesion is detected. Consider proper rescreening of the whole neuroaxis in refractory cases of intracranial hypertension.Keywords: CNS infection, IIH, headache, primary spinal leptomeningeal medulloblastoma
Procedia PDF Downloads 67713 Factors Associated with Overweight and Obesity among Recipients of Antiretroviral Therapy at HIV Clinics in Botswana
Authors: Jose G. Tshikuka, Goabaone Rankgoane-Pono, Mgaywa G. M. D. Magafu, Julius C. Mwita, Tiny Masupe, Fortunat M. Kandanda, Shimeles G. Hamda, Roy Tapera, Mooketsi Molefi, John T. Tlhakanelo
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Background: Factors associated with overweight and obesity among antiretroviral therapy (ART) recipients have not been sufficiently studied in Botswana. We aimed to study (i) the prevalence and trends in overweight/obesity by duration of exposure to ART among recipients, (ii) changes in body mass index (BMI) categories among recipients before ART initiation (BMI-1) and after ART initiation (BMI-2), (iii) associations between ART and overweight/obesity and (iv) factors associated with BMI changes among ART recipients. Methods: A 12 years retrospective record-based review was conducted. Factors potentially associated with BMI change among patients after at least three years of ART exposure were examined using multiple regression model. Adjusted odds ratios (AOR) and their 95% confidence intervals (CIs) were computed. ART regimens, duration of exposure to ART, and recipients’ demographic and biomedical characteristics including the presence or absence of diabetes mellitus related comorbidities (DRC) were investigated as potential factors associated with overweight/obesity. Results: Twenty-nine percent of recipients were overweight, 16.6% had obesity of whom 2.4% were morbidly-obese at the last clinic visit. Overweight/obesity recipients were more likely to be female, to have DRC and less likely to have nadir CD4 count or CD4 count between 201 – 249 cells/mm³. Neither the first-line nor the second-, third-line ART regimens predicted overweight/obesity more than the other and neither did the duration of exposure to ART. No significant linear trends were observed in the prevalence of overweight/obesity by the duration of exposure to ART. Conclusions: These results indicate that overweight/obesity seen among ART recipients is not directly induced by ART. ART used CD4 and/or DRC pathway to induce overweight/obesity seen among recipients; suggesting that, weight gain documented herein is likely a reflection of improved health status that mirrors trends in the general population or a DRC related effect. Weight management programs may be important components of HIV care.Keywords: overweight/obesity, recipients of antiretroviral therapy, HIV/AIDS, Botswana
Procedia PDF Downloads 161712 Prevalence and Pattern of Abnormalities Pap Smear Examination in Women Attending Fertility Clinic in Uniosun Teaching Hospitals, Osun State, Nigeria
Authors: Ayodeji Blessing Ajileye
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Introduction: Infertility is described as failure to conceive after one year of unprotected sexual intercourse. One of the causes of female infertility is caused by cervical abnormalities which may be due to bacterial and parasitological infections, hormonal imbalances of Lentinizing hormone, follicular stimulating hormone, oestrogen hormone and progesterone hormone. Aim of the Study: This study aimed to determine the prevalence and pattern of abnormal cervical Pap smear in women with infertility attending fertility clinics at Uniosun Teaching Hospitals Osogbo, Osun State. Methods: This study was conducted at the fertility clinic of University of Osun Teaching Hospital, Osogbo, Osun State. The study population comprised of 50 infertile women and 50 fertile women who are attending the gynecology clinic of University of Osun Teaching Hospital, Osogbo, Osun State. Questionnaire was used to obtain relevant data. Cervical sample was collected using Ayre’s spatula, two smears were prepared and stained with Papanicolaous and H&E staining techniques. Results were analyzed using frequency table. Results: This study observed the prevalence of abnormal cervical smear among infertility women to be 16(30%), while only 03(6%) were observed among the control group (fertile women). Atypical squamous cells of undetermined significance have the highest abnormalities observed in this study with 30%, about 28% of the Pap smear results were negative for inflammation, while total inflammation observed was 72% among the infertility women. Conclusion: This study concluded that abnormal pap smears in this study is significantly more often in women with infertility as compared with fertile women.Keywords: infertility, oestrogen hormone, pap smears, progesterone hormone
Procedia PDF Downloads 87711 Overexpression of CAS8 Enhances Necroptosis and Metastasis in Iranian Sporadic Colorectal Cancer
Authors: Sayed Ali Garossi, Azar Heidarizadi, Shahla Mohammad Ganji
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Context: Colorectal cancer is the second type of cancer-related mortality globally. Expression of cas8 (caspase 8) is closely connected to growth and metastasis of colorectal cancer.Cas8/Rip1 plays a vital role in the apoptosis pathway and resistance to chemotherapy. The aim of the present study is to investigate the pattern of gene expression in colorectal cancer and compare the differences using Real-Time PCR to find a potential biomarker candidate for colorectal cancer. Methodology: This study conducted real-time PCR to evaluate gene expression of Cas8 in colorectal cancer patients. The gene-specific primer sequences exon–exon junction was designed by OLIGO7 software for the expression of the gene under investigation. Forty-six patient samples without any chemotherapy were selected, including tumoral tissue and adjacent normal tissue samples. The age of the patients was 50 and the size of the tumors was 5.5 cm. The categories were before and after age 50. Findings: Here, we found that Caspase 8 was overexpressed in CRC tissues compared to corresponding adjacent colon tissues (Cas8: 5.2 vs. 1 ratio); high expression of Cas8 was associated with poor overall survival and independent risk factors for the prognosis of CRC patients. Conclusion: In conclusion, our study pioneered the reporting of high Casp8 expression as a predictor of poor prognosis and chemical resistance in CRC patients.Cas8 overexpression suppressed Cas 8 / Rip1-dependent apoptosis and activated the proliferation of tumor cells by activating necroptosis. The necroptosis pathway has also emerged as a new approach to anti-tumor in cancer treatment.Keywords: Cas8, necroptosis, apoptosis, Real-Time PCR
Procedia PDF Downloads 55710 The Effect of Jujube Extract and Resistance Training on the Reduction of Complications Caused by the Induction of Anabolic Steroid Boldenone on the Histopathological Changes of Pancreatic Tissue of Male Wistar Rats
Authors: Sayyed-javad Ziaolhagh, Ali-Reza Saadatifar
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Introduction: Athletes frequently perform anabolic steroid resistance exercise, but the effects of medical doses and abuse along with resistance exercise on structural damage to the Pancreases and also jujube extract are unknown. The aim of this study was to investigate the effects of resistance training on body weight and hip fractures induced by boldenone injection in male rats. Materials and methods: In this experimental study, 30 male Wistar rats aged 8-12 weeks (weight 202±9.34 g) were randomly divided into five groups: control, boldenone, extract of iujuba+boldenone, boldenone+resistance training and boldenone+resistance training +extract of jujuba. The resistance training program included climbing the ladder for 8 weeks, 3 days a week, 1 session training in a day and each session consisted of the 3 sets and 5 repetitions. Injection was conducted in depth in the hamstring once a week on an appointed day. After anesthesia, autopsy was performed, and the cardiac tissue was isolated. Results: Results showed that boldenone caused tissue damage, congestion, and nuclei unclear and diffuse. In the group "resistance + Boldenone," The Pancreases tissue showed a high degree of hyperemia, and the muscle cells were somewhat abnormal. In boldenone + jujube, the appearance of the tissue was normal, and the rejuvenating effect was visible. Conclusion: Boldenone appears to cause structural damage to the Pancreases tissue. Strength training with Jujube Extract can reduce part of the pancreatic system disorders (necrosis and inflammation) caused by anabolic steroid use.Keywords: boldenone, Jujube extract, pancreases tissue, resistance training
Procedia PDF Downloads 72709 Hemato-Biochemical Studies on Naturally Infected Camels with Trypanosomiasis
Authors: Khalid Mehmood, Riaz Hussain, Rao Z. Abbas, Tariq Abbas, Abdul Ghaffar, Ahmad J. Sabir
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Blood born diseases such as trypanosomiasis have negative impacts on health, production and working efficiency of camels in different camel-rearing areas of the world including Pakistan. In present study blood samples were collected from camels kept at the desert condition of cholistan to estimate the prevalence of trypanosomiasis and hemato-biochemical changes in naturally infected cases. Results showed an overall 9.31% prevalence of trypanosomiasis in camels. Various clinical signs such as pyrexia, occasional shivering, inappetence, urticaria, swelling, lethargy, going down in condition and edema of pads were observed in few cases. The statistical analysis did not show significant association of age and sex with trypanosomiasis. However, results revealed significantly decreased values of total erythrocyte counts, packed cell volume, hemoglobin concentration, mean corpuscular hemoglobin concentration, serum total proteins and albumin while increased values of mean corpuscular volume was recorded in infected animals as compared to healthy. A significant (P<0.01) increased values of total leukocyte count, monocyte, lymphocyte, neutrophils, and eosinophils was recorded in infected animals. Moreover, microscopic examination of blood films obtained from naturally infected cases showed the presence of parasite and various morphological changes in cells such as stomatocyte, hyperchromasia, and polychromasia. Significantly increased values of different hepatic enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were also recorded.Keywords: camel, hematological indices, serum enzymes, Trypanosomiasis
Procedia PDF Downloads 528708 Quartz Crystal Microbalance Based Hydrophobic Nanosensor for Lysozyme Detection
Authors: F. Yılmaz, Y. Saylan, A. Derazshamshir, S. Atay, A. Denizli
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Quartz crystal microbalance (QCM), high-resolution mass-sensing technique, measures changes in mass on oscillating quartz crystal surface by measuring changes in oscillation frequency of crystal in real time. Protein adsorption techniques via hydrophobic interaction between protein and solid support, called hydrophobic interaction chromatography (HIC), can be favorable in many cases. Some nanoparticles can be effectively applied for HIC. HIC takes advantage of the hydrophobicity of proteins by promoting its separation on the basis of hydrophobic interactions between immobilized hydrophobic ligands and nonpolar regions on the surface of the proteins. Lysozyme is found in a variety of vertebrate cells and secretions, such as spleen, milk, tears, and egg white. Its common applications are as a cell-disrupting agent for extraction of bacterial intracellular products, as an antibacterial agent in ophthalmologic preparations, as a food additive in milk products and as a drug for treatment of ulcers and infections. Lysozyme has also been used in cancer chemotherapy. The aim of this study is the synthesis of hydrophobic nanoparticles for Lysozyme detection. For this purpose, methacryoyl-L-phenylalanine was chosen as a hydrophobic matrix. The hydrophobic nanoparticles were synthesized by micro-emulsion polymerization method. Then, hydrophobic QCM nanosensor was characterized by Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, atomic force microscopy (AFM) and zeta size analysis. Hydrophobic QCM nanosensor was tested for real-time detection of Lysozyme from aqueous solution. The kinetic and affinity studies were determined by using Lysozyme solutions with different concentrations. The responses related to a mass (Δm) and frequency (Δf) shifts were used to evaluate adsorption properties.Keywords: nanosensor, HIC, lysozyme, QCM
Procedia PDF Downloads 349707 Allergenic Potential of Airborne Algae Isolated from Malaysia
Authors: Chu Wan-Loy, Kok Yih-Yih, Choong Siew-Ling
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The human health risks due to poor air quality caused by a wide array of microorganisms have attracted much interest. Airborne algae have been reported as early as 19th century and they can be found in the air of tropic and warm atmospheres. Airborne algae normally originate from water surfaces, soil, trees, buildings and rock surfaces. It is estimated that at least 2880 algal cells are inhaled per day by human. However, there are relatively little data published on airborne algae and its related adverse health effects except sporadic reports of algae associated clinical allergenicity. A collection of airborne algae cultures has been established following a recent survey on the occurrence of airborne algae in indoor and outdoor environments in Kuala Lumpur. The aim of this study was to investigate the allergenic potential of the isolated airborne green and blue-green algae, namely Scenedesmus sp., Cylindrospermum sp. and Hapalosiphon sp.. The suspensions of freeze-dried airborne algae were adminstered into balb-c mice model through intra-nasal route to determine their allergenic potential. Results showed that Scenedesmus sp. (1 mg/mL) increased the systemic Ig E levels in mice by 3-8 fold compared to pre-treatment. On the other hand, Cylindrospermum sp. and Hapalosiphon sp. at similar concentration caused the Ig E to increase by 2-4 fold. The potential of airborne algae causing Ig E mediated type 1 hypersensitivity was elucidated using other immunological markers such as cytokine interleukin (IL)- 4, 5, 6 and interferon-ɣ. When we compared the amount of interleukins in mouse serum between day 0 and day 53 (day of sacrifice), Hapalosiphon sp. (1mg/mL) increased the expression of IL4 and 6 by 8 fold while the Cylindrospermum sp. (1mg/mL) increased the expression of IL4 and IFɣ by 8 and 2 fold respectively. In conclusion, repeated exposure to the three selected airborne algae may stimulate the immune response and generate Ig E in a mouse model.Keywords: airborne algae, respiratory, allergenic, immune response, Malaysia
Procedia PDF Downloads 240706 Deuterium Effect on the Growth of the Fungus Aspergillus Fumigatus and Candida Albicans
Authors: Farzad Doostishoar, Abdolreza Hasanzadeh, Seyed Amin Ayatolahi Mousavi
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Introduction and Goals: Deuterium has different action from its isotopes hydrogen in chemical reactions and biochemical processes. It is not a significant difference in heavier atoms between the behavior of heavier isotope and the lighter One but for very lighter atoms it is significant . According to that most of the weight of all creatures body is water natural rate can be significant. In this article we want to study the effect of reduced deuterium on the fungus cell. If we saw the dependence of deuterium concentration of environment on the cells growth we can test this in invivo models too. Methods: First we measured deuterium concentration of the distillated water this analyze was operated by Arak’s heavy water company. Then the deuterium was diluted to ½ ¼ 1/8 1/16 by adding water free of deuterium for making media. In tree of samples the deuterium concentration was increased by adding D2O up to 10,50,100 times more concentrated. For candida albicans growth we used sabor medium and for aspergillus fomigatis growth we used sabor medium containing chloramphenicol. After culturing the funguses species we put the mediums for each species in the shaker incubator for 10 days in 25 centigrade. In different days and times the plates were studied morphologically and some microscopic characteristics were studied too. This experiments and cultures were repeated 3 times. Results: Statistical analyzes by paired-sample T test showed that aspergilus fomigatoos growth was decreased in concentration of 72 ppm( half deuterium concentration of negative control) significantly. In deuterium concentration reduction the growth reduce into the negative control significantly. The project results showed that candida albicans was sensitive to reduce and decrease of the deuterium in all concentrations.Keywords: deuterium, cancer cell, growth, candida albicans
Procedia PDF Downloads 401705 Performance Evaluation of the CareSTART S1 Analyzer for Quantitative Point-Of-Care Measurement of Glucose-6-Phosphate Dehydrogenase Activity
Authors: Haiyoung Jung, Mi Joung Leem, Sun Hwa Lee
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Background & Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic abnormality that results in an inadequate amount of G6PD, leading to increased susceptibility of red blood cells to reactive oxygen species and hemolysis. The present study aimed to evaluate the careSTARTTM S1 analyzer for measuring G6PD activity to hemoglobin (Hb) ratio. Methods: Precision for G6PD activity and hemoglobin measurement was evaluated using control materials with two levels on five repeated runs per day for five days. The analytic performance of the careSTARTTM S1 analyzer was compared with spectrophotometry in 40 patient samples. Reference ranges suggested by the manufacturer were validated in 20 healthy males and females each. Results: The careSTARTTM S1 analyzer demonstrated precision of 6.0% for low-level (14~45 U/dL) and 2.7% for high-level (60~90 U/dL) control in G6PD activity, and 1.4% in hemoglobin (7.9~16.3 u/g Hb). A comparison study of G6PD to Hb ratio between the careSTARTTM S1 analyzer and spectrophotometry showed an average difference of 29.1% with a positive bias of the careSTARTTM S1 analyzer. All normal samples from the healthy population were validated for the suggested reference range for males (≥2.19 U/g Hb) and females (≥5.83 U/g Hb). Conclusion: The careSTARTTM S1 analyzer demonstrated good analytical performance and can replace the current spectrophotometric measurement of G6PD enzyme activity. In the aspect of the management of clinical laboratories, it can be a reasonable option as a point-of-care analyzer with minimal handling of samples and reagents, in addition to the automatic calculation of the ratio of measured G6PD activity and Hb concentration, to minimize any clerical errors involved with manual calculation.Keywords: POCT, G6PD, performance evaluation, careSTART
Procedia PDF Downloads 65704 Hepatoprotective Assessment of L-Ascorbate 1-(2-Hydroxyethyl)-4,6-Dimethyl-1, 2-Dihydropyrimidine-2-On Exposure to Carbon Tetrachloride
Authors: Nail Nazarov, Alexandra Vyshtakalyuk, Vyacheslav Semenov, Irina Galyametdinova, Vladimir Zobov, Vladimir Reznik
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Among hepatic pyrimidine used as a means of stimulating protein synthesis and recovery of liver cells in her damaged toxic and infectious etiology. When an experimental toxic hepatitis hepatoprotective activity detected some pyrimidine derivatives. There are literature data on oksimetiluratcila hepatoprotective effect. For analogs of pyrimidine nucleobases - drugs Methyluracilum pentoxy and hepatoprotective effect of weakly expressed. According to the American scientists broad spectrum of biological activity, including hepatoprotective properties, have a 2,4-dioxo-5-arilidenimino uracils. Influenced Xymedon medicinal preparation (1- (beta-hydroxyethyl) -4,6-dimethyl-1,2-dihydro-2-oksopirimidin) developed as a means of stimulating the regeneration of tissue revealed increased activity of microsomal oxidases human liver. In studies on the model of toxic liver damage in rats have shown hepatoprotective effect xymedon and stimulating its impact on the recovery of the liver tissue. Hepatoprotective properties of the new compound in the series of pyrimidine derivatives L-ascorbate 1-(2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropirimidine-2-one synthesized on the basis Xymedon preparation were firstly investigated on rats under the carbon tetrachloride action. It was shown the differences of biochemical parameters from the reference value and severity of structural-morphological liver violations decreased in comparison with control group under the influence of the compound injected before exposure carbon tetrachloride. Hepatoprotective properties of the investigated compound were more pronounced in comparison with Xymedon.Keywords: hepatoprotectors, pyrimidine derivatives, toxic liver damage, xymedon
Procedia PDF Downloads 427703 Mechanisms and Regulation of the Bi-directional Motility of Mitotic Kinesin Nano-motors
Authors: Larisa Gheber
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Mitosis is an essential process by which duplicated genetic information is transmitted from mother to daughter cells. Incorrect chromosome segregation during mitosis can lead to genetic diseases, chromosome instability and cancer. This process is mediated by a dynamic microtubule-based intracellular structure, the mitotic spindle. One of the major factors that govern the mitotic spindle dynamics are the kinesin-5 biological nano motors that were believed to move unidirectionally on the microtubule filaments, using ATP hydrolysis, thus performing essential functions in mitotic spindle dynamics. Surprisingly, several reports from our and other laboratories have demonstrated that some kinesin-5 motors are bi-directional: they move in minus-end direction on the microtubules as single-molecules and can switch directionality under a number of conditions. These findings broke a twenty-five-years old dogma regarding kinesin directionality (1, 2). The mechanism of this bi-directional motility and its physiological significance remain unclear. To address this unresolved problem, we apply an interdisciplinary approach combining live cell imaging, biophysical single molecule, and structural experiments to examine the activity of these motors and their mutated variants in vivo and in vitro. Our data shows that factors such as protein phosphorylation (3, 4), motor clustering on the microtubules (5, 6) and structural elements (7, 8) regulate the bi-directional motility of kinesin motors. We also show, using Cryo-EM, that bi-directional kinesin motors obtain non-canonical microtubule binding, which is essential to their special motile properties and intracellular functions. We will discuss the implication of these findings to mechanism bi-directional motility and physiological roles in mitosis.Keywords: mitosis, cancer, kinesin, microtubules, biochemistry, biophysics
Procedia PDF Downloads 81702 The Role of a Novel DEAD-Box Containing Protein in NLRP3 Inflammasome Activation
Authors: Yi-Hui Lai, Chih-Hsiang Yang, Li-Chung Hsu
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The inflammasome is a protein complex that modulates caspase-1 activity, resulting in proteolytic cleavage of proinflammatory cytokines such as IL-1β and IL-18, into their bioactive forms. It has been shown that the inflammasomes play a crucial role in the clearance of pathogenic infection and tissue repair. However, dysregulated inflammasome activation contributes to a wide range of human diseases such as cancers and auto-inflammatory diseases. Yet, regulation of NLRP3 inflammasome activation remains largely unknown. We discovered a novel DEAD box protein, whose biological function has not been reported, not only negatively regulates NLRP3 inflammasome activation by interfering NLRP3 inflammasome assembly and cellular localization but also mitigate pyroptosis upon pathogen evasion. The DEAD-box protein is the first DEAD-box protein gets involved in modulation of the inflammasome activation. In our study, we found that caspase-1 activation and mature IL-1β production were largely enhanced upon LPS challenge in the DEAD box-containing protein- deleted THP-1 macrophages and bone marrow-derived macrophages (BMDMs). In addition, this DEAD box-containing protein migrates from the nucleus to the cytoplasm upon LPS stimulation, which is required for its inhibitory role in NLRP3 inflammasome activation. The DEAD box-containing protein specifically interacted with the LRR motif of NLRP3 via its DEAD domain. Furthermore, due to the crucial role of the NLRP3 LRR domain in the recruitment of NLRP3 to mitochondria and binding to its adaptor ASC, we found that the interaction of NLRP3 and ASC was downregulated in the presence of the DEAD box-containing protein. In addition to the mechanical study, we also found that this DEAD box protein protects host cells from inflammasome-triggered cell death in response to broad-ranging pathogens such as Candida albicans, Streptococcus pneumoniae, etc., involved in nosocomial infections and severe fever shock. Collectively, our results suggest that this novel DEAD box molecule might be a key therapeutic strategy for various infectious diseases.Keywords: inflammasome, inflammation, innate immunity, pyroptosis
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