Search results for: drug resistant bacteria
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4050

Search results for: drug resistant bacteria

1980 Wood Framing Roof Resistant Support for Hurricane

Authors: P. Hajyalikhani, E. Gilmore, C. Petty, J. Duron

Abstract:

Wood framed construction is the most popular method of construction for residential buildings. The typical roof framing for wood-framed buildings is sloped and consists of several structural members, such as rafters, hips, and valleys that link to the ridge and ceiling joists. The most common type of wood framing used is platform framing, also known as stick framing. Failures of the wood framing structures are among the most common types of wind damage in densely populated regions. Wood-framed buildings are under uplift during tornadoes and hurricanes which cause the failure in the roof. The bracing long structure members such as hip and valley have a large impact on the resilience of wood-framed buildings. As a result, the common failures in wood-framed buildings are reviewed, and the critical support locations for lengthy hips and valleys with various slopes are analyzed and recommended.

Keywords: rafters, hips, valleys, hip, ceiling joist, roof failures, residential and commercial structures, hurricane, tornadoes, building codes

Procedia PDF Downloads 68
1979 Methotrexate Associated Skin Cancer: A Signal Review of Pharmacovigilance Center

Authors: Abdulaziz Alakeel, Abdulrahman Alomair, Mohammed Fouda

Abstract:

Introduction: Methotrexate (MTX) is an antimetabolite used to treat multiple conditions, including neoplastic diseases, severe psoriasis, and rheumatoid arthritis. Skin cancer is the out-of-control growth of abnormal cells in the epidermis, the outermost skin layer, caused by unrepaired DNA damage that triggers mutations. These mutations lead the skin cells to multiply rapidly and form malignant tumors. The aim of this review is to evaluate the risk of skin cancer associated with the use of methotrexate and to suggest regulatory recommendations if required. Methodology: Signal Detection team at Saudi Food and Drug Authority (SFDA) performed a safety review using National Pharmacovigilance Center (NPC) database as well as the World Health Organization (WHO) VigiBase, alongside with literature screening to retrieve related information for assessing the causality between skin cancer and methotrexate. The search conducted in July 2020. Results: Four published articles support the association seen while searching in literature, a recent randomized control trial published in 2020 revealed a statistically significant increase in skin cancer among MTX users. Another study mentioned methotrexate increases the risk of non-melanoma skin cancer when used in combination with immunosuppressant and biologic agents. In addition, the incidence of melanoma for methotrexate users was 3-fold more than the general population in a cohort study of rheumatoid arthritis patients. The last article estimated the risk of cutaneous malignant melanoma (CMM) in a cohort study shows a statistically significant risk increase for CMM was observed in MTX exposed patients. The WHO database (VigiBase) searched for individual case safety reports (ICSRs) reported for “Skin Cancer” and 'Methotrexate' use, which yielded 121 ICSRs. The initial review revealed that 106 cases are insufficiently documented for proper medical assessment. However, the remaining fifteen cases have extensively evaluated by applying the WHO criteria of causality assessment. As a result, 30 percent of the cases showed that MTX could possibly cause skin cancer; five cases provide unlikely association and five un-assessable cases due to lack of information. The Saudi NPC database searched to retrieve any reported cases for the combined terms methotrexate/skin cancer; however, no local cases reported up to date. The data mining of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by the WHO Uppsala Monitoring Centre to measure the reporting ratio. Positive IC reflects higher statistical association, while negative values translated as a less statistical association, considering the null value equal to zero. Results showed that a combination of 'Methotrexate' and 'Skin cancer' observed more than expected when compared to other medications in the WHO database (IC value is 1.2). Conclusion: The weighted cumulative pieces of evidence identified from global cases, data mining, and published literature are sufficient to support a causal association between the risk of skin cancer and methotrexate. Therefore, health care professionals should be aware of this possible risk and may consider monitoring any signs or symptoms of skin cancer in patients treated with methotrexate.

Keywords: methotrexate, skin cancer, signal detection, pharmacovigilance

Procedia PDF Downloads 114
1978 Bioactivity of Peptides from Two Mushrooms

Authors: Parisa Farzaneh, Azade Harati

Abstract:

Mushrooms, or macro-fungi, as an important superfood, contain many bioactive compounds, particularly bio-peptides. In this research, mushroom proteins were extracted by buffer or buffer plus salt (0.15 M), along with an ultrasound bath to extract the intercellular protein. As a result, the highest amount of proteins in mushrooms were categorized into albumin. Proteins were also hydrolyzed and changed into peptides through endogenous and exogenous proteases, including gastrointestinal enzymes. The potency of endogenous proteases was also higher in Agaricus bisporus than Terfezia claveryi, as their activity ended at 75 for 15 min. The blanching process, endogenous enzymes, the mixture of gastrointestinal enzymes (pepsin-trypsin-α-chymotrypsin or trypsin- α-chymotrypsin) produced the different antioxidant and antibacterial hydrolysates. The peptide fractions produced with different cut-off ultrafilters also had various levels of radical scavenging, lipid peroxidation inhibition, and antibacterial activities. The bio-peptides with superior bioactivities (less than 3 kD of T. claveryi) were resistant to various environmental conditions (pH and temperatures). Therefore, they are good options to be added to nutraceutical and pharmaceutical preparations or functional foods, even during processing.

Keywords: bio-peptide, mushrooms, gastrointestinal enzymes, bioactivity

Procedia PDF Downloads 60
1977 The Effect of Solution pH of Chitosan on Antimicrobial Properties of Nylon 6,6 Fabrics

Authors: Nilüfer Yıldız Varan

Abstract:

The antimicrobial activities of chitosan against various bacteria and fungi are well known, and the antimicrobial activity of chitosan depends on pH. This study investigates the antimicrobial activity at different pH levels. Nylon 6,6 fabrics were treated with different chitosan solutions. Additionally, samples were treated also in basic conditions to see the antimicrobial activities. AATCC Test Method 100 was followed to evaluate the antimicrobial activity using Staphylococcus aureus ATCC 6538 test inoculum. The pH of the chitosan solutions was controlled below 6.5 since chitosan shows its antimicrobial activity only in acidic conditions because of its poor solubility above 6.5. In basic conditions, the samples did not show any antimicrobial activity. It appears from SEM images that the bonded chitosan in the structures exists. In acidic media (ph < 6.5), all samples showed antimicrobial activity. No correlation was found between pH levels and antimicrobial activity in acidic media.

Keywords: chitosan, nylon 6, 6, crosslinking, pH stability, antimicrobial

Procedia PDF Downloads 219
1976 Development of a Bacterial Resistant Concrete for Use in Low Cost Kitchen Floors

Authors: S. S. Mahlangu, R. K. K. Mbaya, D. D. Delport, H. Van. Zyl

Abstract:

The degrading effect due to bacterial growth on the structural integrity of concrete floor surfaces is predictable; this consequently cause development of surface micro cracks in which organisms penetrate through resulting in surface spalling. Hence, the need to develop mix design meeting the requirement of floor surfaces exposed to aggressive agent to improve certain material properties with good workability, extended lifespan and low cost is essential. In this work, tests were performed to examine the microbial activity on kitchen floor surfaces and the effect of adding admixtures. The biochemical test shows the existence of microorganisms (E.coli, Streptococcus) on newly casted structure. Of up to 6% porosity was reduced and improvement on structural integrity was observed upon adding mineral admixtures from the concrete mortar. The SEM result after 84 days of curing specimens, shows that chemical admixtures have significant role to enable retard bacterial penetration and good quality structure is achieved.

Keywords: admixture, organisms, porosity, strength

Procedia PDF Downloads 236
1975 Rapid Detection of MBL Genes by SYBR Green Based Real-Time PCR

Authors: Taru Singh, Shukla Das, V. G. Ramachandran

Abstract:

Objectives: To develop SYBR green based real-time PCR assay to detect carbapenemases (NDM, IMP) genes in E. coli. Methods: A total of 40 E. coli from stool samples were tested. Six were previously characterized as resistant to carbapenems and documented by PCR. The remaining 34 isolates previously tested susceptible to carbapenems and were negative for these genes. Bacterial RNA was extracted using manual method. The real-time PCR was performed using the Light Cycler III 480 instrument (Roche) and specific primers for each carbapenemase target were used. Results: Each one of the two carbapenemase gene tested presented a different melting curve after PCR amplification. The melting temperature (Tm) analysis of the amplicons identified was as follows: blaIMP type (Tm 82.18°C), blaNDM-1 (Tm 78.8°C). No amplification was detected among the negative samples. The results showed 100% concordance with the genotypes previously identified. Conclusions: The new assay was able to detect the presence of two different carbapenemase gene type by real-time PCR.

Keywords: resistance, b-lactamases, E. coli, real-time PCR

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1974 Self-Assembled ZnFeAl Layered Double Hydroxides as Highly Efficient Fenton-Like Catalysts

Authors: Marius Sebastian Secula, Mihaela Darie, Gabriela Carja

Abstract:

Ibuprofen is a non-steroidal anti-inflammatory drug (NSAIDs) and is among the most frequently detected pharmaceuticals in environmental samples and among the most widespread drug in the world. Its concentration in the environment is reported to be between 10 and 160 ng L-1. In order to improve the abatement efficiency of this compound for water source prevention and reclamation, the development of innovative technologies is mandatory. AOPs (advanced oxidation processes) are known as highly efficient towards the oxidation of organic pollutants. Among the promising combined treatments, photo-Fenton processes using layered double hydroxides (LDHs) attracted significant consideration especially due to their composition flexibility, high surface area and tailored redox features. This work presents the self-supported Fe, Mn or Ti on ZnFeAl LDHs obtained by co-precipitation followed by reconstruction method as novel efficient photo-catalysts for Fenton-like catalysis. Fe, Mn or Ti/ZnFeAl LDHs nano-hybrids were tested for the degradation of a model pharmaceutical agent, the anti-inflammatory agent ibuprofen, by photocatalysis and photo-Fenton catalysis, respectively, by means of a lab-scale system consisting of a batch reactor equipped with an UV lamp (17 W). The present study presents comparatively the degradation of Ibuprofen in aqueous solution UV light irradiation using four different types of LDHs. The newly prepared Ti/ZnFeAl 4:1 catalyst results in the best degradation performance. After 60 minutes of light irradiation, the Ibuprofen removal efficiency reaches 95%. The slowest degradation of Ibuprofen solution occurs in case of Fe/ZnFeAl 4:1 LDH, (67% removal efficiency after 60 minutes of process). Evolution of Ibuprofen degradation during the photo Fenton process is also studied using Ti/ZnFeAl 2:1 and 4:1 LDHs in the presence and absence of H2O2. It is found that after 60 min the use of Ti/ZnFeAl 4:1 LDH in presence of 100 mg/L H2O2 leads to the fastest degradation of Ibuprofen molecule. After 120 min, both catalysts Ti/ZnFeAl 4:1 and 2:1 result in the same value of removal efficiency (98%). In the absence of H2O2, Ibuprofen degradation reaches only 73% removal efficiency after 120 min of degradation process. Acknowledgements: This work was supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNCS - UEFISCDI, project number PN-II-RU-TE-2014-4-0405.

Keywords: layered double hydroxide, advanced oxidation process, micropollutant, heterogeneous Fenton

Procedia PDF Downloads 229
1973 Seismic Response Analysis of Frame Structures Based on Super Joint Element Model

Authors: Li Xu, Yang Hong, T. Zhao Wen

Abstract:

Experimental results of many RC beam-column subassemblage indicate that slippage of longitudinal beam rebar within the joint and the shear deformation of joint core have significant influence on seismic behavior of the subassemblage. However, rigid joint assumption has been generally used in the seismic response analysis of RC frames, in which two kinds of inelastic deformation of joint have been ignored. Based on OpenSees platform, ‘Super Joint Element Model’ with more detailed inelastic mechanism is used to simulate the inelastic response of joints. Two finite element models of typical RC plane frame, namely considering or ignoring the inelastic deformation of joint respectively, were established and analyzed under seven strong earthquake waves. The simulated global and local inelastic deformations of the RC plane frame is shown and discussed. The analyses also confirm the security of the earthquake-resistant frame designed according to Chinese codes.

Keywords: frame structure, beam-column joint, longitudinal bar slippage, shear deformation, nonlinear analysis

Procedia PDF Downloads 409
1972 Anticorrosive Polyurethane Clear Coat with Self-Cleaning Character

Authors: Nihit Madireddi, P. A. Mahanwar

Abstract:

We have aimed to produce a self-cleaning transparent polymer coating with polyurethane (PU) matrix as the latter is highly solvent, chemical and weather resistant having good mechanical properties. Nano-silica modified by 1H, 1H, 2H, 2H-perflurooctyltriethoxysilane was incorporated into the PU matrix for attaining self-cleaning ability through hydrophobicity. The modification was confirmed by particle size analysis and scanning electron microscopy (SEM). Thermo-gravimetric (TGA) studies were carried to ascertain the grafting of silane onto the silica. Several coating formulations were prepared by varying the silica loading content and compared to a commercial equivalent. The effect of dispersion and the morphology of the coated films were assessed by SEM analysis. All coating standardized tests like solvent resistance, adhesion, flexibility, acid, alkali, gloss etc. have been performed as per ASTM standards. Water contact angle studies were conducted to analyze the hydrophobic character of the coating. In addition, the coatings were also subjected to salt spray and accelerated weather testing to analyze the durability of the coating.

Keywords: FAS, nano-silica, PU clear coat, self-cleaning

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1971 The Effect of Masonry Infills on the Seismic Response of Reinforced Concrete Structures

Authors: Mohammad Reza Ameri, Ali Massumi, Behnam Mahboubi

Abstract:

The performance of masonry infilled frames during the past earthquakes shows that the infill panels play a major role as earthquake-resistant elements. The present study examines the influence of infill panels on seismic behavior of RC frame structures. For this purpose, several low- and mid-rise RC frames (two-, four-, seven-, and ten story) were numerically investigated. Reinforced masonry infill panels were then placed within the frames and the models were subjected to several nonlinear incremental static and dynamic analyses. The results of analyses showed that the use of reinforced masonry infill panels in RC frame structures can have beneficial effects on structural performance. It was confirmed that the use of masonry infill panels results in an increment in strength and stiffness of the framed buildings, followed by a reduction in displacement demand for the structural systems.

Keywords: reinforced masonry infill panels, nonlinear static analysis, incremental dynamic analysis, low-rise reinforced concrete frames, mid-rise reinforced concrete frames

Procedia PDF Downloads 320
1970 Safety Assessment of Traditional Ready-to-Eat Meat Products Vended at Retail Outlets in Kebbi and Sokoto States, Nigeria

Authors: M. I. Ribah, M. Jibir, Y. A. Bashar, S. S. Manga

Abstract:

Food safety is a significant and growing public health problem in the world and Nigeria as a developing country, since food-borne diseases are important contributors to the huge burden of sickness and death of humans. In Nigeria, traditional ready-to-eat meat products (RTE-MPs) like balangu, tsire, guru and dried meat products like kilishi, dambun nama, banda, were reported to be highly appreciated because of their eating qualities. The consumption of these products was considered as safe due to the treatments that are usually involved during their production process. However, during processing and handling, the products could be contaminated by pathogens that could cause food poisoning. Therefore, a hazard identification for pathogenic bacteria on some traditional RTE-MPs was conducted in Kebbi and Sokoto States, Nigeria. A total of 116 RTE-MPs (balangu-38, kilishi-39 and tsire-39) samples were obtained from retail outlets and analyzed using standard cultural microbiological procedures in general and selective enrichment media to isolate the target pathogens. A six-fold serial dilution was prepared and using the pour plating method, colonies were counted. Serial dilutions were selected based on the prepared pre-labeled Petri dishes for each sample. A volume of 10-12 ml of molten Nutrient agar cooled to 42-45°C was poured into each Petri dish and 1 ml each from dilutions of 102, 104 and 106 for every sample was respectively poured on a pre-labeled Petri plate after which colonies were counted. The isolated pathogens were identified and confirmed after series of biochemical tests. Frequencies and percentages were used to describe the presence of pathogens. The General Linear Model was used to analyze data on pathogen presence according to RTE-MPs and means were separated using the Tukey test at 0.05 confidence level. Of the 116 RTE-MPs samples collected, 35 (30.17%) samples were found to be contaminated with some tested pathogens. Prevalence results showed that Escherichia coli, salmonella and Staphylococcus aureus were present in the samples. Mean total bacterial count was 23.82×106 cfu/g. The frequency of individual pathogens isolated was; Staphylococcus aureus 18 (15.51%), Escherichia coli 12 (10.34%) and Salmonella 5 (4.31%). Also, among the RTE-MPs tested, the total bacterial counts were found to differ significantly (P < 0.05), with 1.81, 2.41 and 2.9×104 cfu/g for tsire, kilishi, and balangu, respectively. The study concluded that the presence of pathogenic bacteria in balangu could pose grave health risks to consumers, and hence, recommended good manufacturing practices in the production of balangu to improve the products’ safety.

Keywords: ready-to-eat meat products, retail outlets, public health, safety assessment

Procedia PDF Downloads 133
1969 ECOSURF EH3 - A Taq DNA Polymerase Enhancer

Authors: Kimberley Phoena Fan, Yu Zhang

Abstract:

ECOSURF™ EH-3 Surfactant (EH3) is a nonionic surfactant and has superior wetting and excellent oil removal properties. It is biodegradable with low toxicity and meets or exceeds US EPA Design for the Environment Criteria, and is widely used as a home cleaner, commercial and industrial degreaser. We have recently found that EH3 also possesses a special function which is characterized as an enhancer to Taq DNA polymerase and ameliorator to reduce the effects of PCR inhibitors, i.e., blood, urea, Guanidinium thiocyanate, Humic acids, polyphenol, and Polysaccharides. This is a new kind of PCR enhancer that does not work on relieving secondary structures of GC-rich templates. We have compared EH3’s effects on Taq DNA Polymerase along with other well-known enhancers, such as DMSO, betaine, and BSA, using GC rich or deficient template and found that, unlike DMSO and Betaine, the EH3 boosting effect on PCR reaction is not through reducing Tm. The results show the same increase of PCR products regardless of the GC contents or secondary structures. The mechanism of EH3 enhancing PCR is through its direct interaction with or stimulation of the DNA polymerase and making the enzymes more resistant to inhibitors in the presence of EH3. This phenomenon has first been observed for EH3, a new type of PCR enzyme enhancer. Subsequent research also shows that a series of similar surfactants boost Taq DNA polymerase as well.

Keywords: EH3, DNA, polymerase, enhancer, raw biological samples

Procedia PDF Downloads 139
1968 Effect of a Synthetic Platinum-Based Complex on Autophagy Induction in Leydig TM3 Cells

Authors: Ezzati Givi M., Hoveizi E., Nezhad Marani N.

Abstract:

Platinum-based anticancer therapeutics are the most widely used drugs in clinical chemotherapy but have major limitations and various side effects in clinical applications. Gonadotoxicity and sterility is one of the most common complications for cancer survivors, which seem to be drug-specific and dose-related. Therefore, many efforts have been dedicated to discovering a new structure of platinum-based anticancer agents with improved therapeutic index, fewer side effects. In this regard, new Pt(II)-phosphane complexes containing heterocyclic thionate ligands (PCTL) have been synthesized, which show more potent antitumor activities in comparison to cisplatin. Cisplatin, the best leading metal-based antitumor drug in the field, induces testicular toxicity on Leydig and Sertoli cells leading to serious side effects such as azoospermia and infertility. Therefore in the present study, we aimed to investigate the cytotoxicity effect of PCTL on mice TM4 Sertoli cells with particular emphasis on the role of autophagy in comparison to cisplatin. In this study, an MTT assay was performed to evaluate the IC50 of PCTL and to analyze the TM3 Leydig cell's viability. Cells morphology was evaluated via invert microscope and Changing in morphology for nuclei swelling or autophagic vacuoles formation were assessed by DAPI and MDC staining. Testosterone production in the culture medium was measured using an ELISA kit. Finally, the expression of Autophagy-related genes, Atg5, Beclin1 and p62, were analyzed by qPCR. Based on the obtained results by MTT, the IC50 value of PCTL was 50 μM in TM3 cells and cytotoxic effects was in a dose- and time-dependent manner. Cells morphological changes investigated by inverted microscopy, DAPI, and MDC staining which showed the cytotoxic concentrations of PCTL was significantly higher than cisplatin in the treated TM3 Leydig cells. The results of PCR showed a lack of expression of the p62, Atg5 and Beclin1 gene in TM3 cells treated with PCTL in comparison to cisplatin and control groups. It should be noted that the effects of 25 μM PCTL concentration on TM3 cells have been associated with increased testosterone production and secretion, which requires further study to explain the possible causes and involved molecular mechanisms. The results of the study showed that the PCTL had less-lethal effects on TM3 cells in comparison to cisplatin and probably did not induce autophagy in TM3 cells.

Keywords: platinum-based anticancer agents, cisplatin, Leydig TM3 cells, autophagy

Procedia PDF Downloads 128
1967 Diversified Farming and Agronomic Interventions Improve Soil Productivity, Soybean Yield and Biomass under Soil Acidity Stress

Authors: Imran, Murad Ali Rahat

Abstract:

One of the factors affecting crop production and nutrient availability is acidic stress. The most important element decreasing under acidic stress conditions is phosphorus deficiency, which results in stunted growth and yield because of inefficient nutrient cycling. At the Agriculture Research Institute Mingora Swat, Pakistan, tests were carried out for the first time throughout the course of two consecutive summer seasons in 2016 (year 1) and 2017 (year 2) with the goal of increasing crop productivity and nutrient availability under acidic stress. Three organic supplies (peach nano-black carbon, compost, and dry-based peach wastes), three phosphorus rates, and two advantageous microorganisms (Trichoderma and PSB) were incorporated in the experimental treatments. The findings showed that, in conditions of acid stress, peach organic sources had a significant impact on yield and yield components. The application of nano-black carbon produced the greatest thousand seed weight of 164.6 g among organic sources, however the use of phosphorus solubilizing bacteria (PSB) for seed inoculation increased the thousand seed weight of beneficial microbes when compared to Trichoderma soil application. The thousand seed weight was significantly impacted by the quantities of phosphorus. The treatment of 100 kg P ha-1 produced the highest thousand seed weight (167.3 g), which was followed by 75 kg P ha-1 (162.5 g). Compost amendments provided the highest seed yield (2,140 kg ha-1) and were comparable to the application of nano-black carbon (2,120 kg ha-1). With peach residues, the lowest seed output (1,808 kg ha-1) was observed.Compared to seed inoculation with PSB (1,913 kg ha-1), soil treatment with Trichoderma resulted in the maximum seed production (2,132 kg ha-1). Applying phosphorus to the soybean crop greatly increased its output. The highest seed yield (2,364 kg ha-1) was obtained with 100 kg P ha-1, which was comparable to 75 kg P ha-1 (2,335 kg ha-1), while the lowest seed yield (1,569 kg ha-1) was obtained with 50 kg P ha-1. The average values showed that compared to control plots (3.3 g kg-1), peach organic sources produced greatest SOC (10.0 g kg-1). Plots with treated soil had a maximum soil P of 19.7 mg kg-1, while plots under stress had a maximum soil P of 4.8 mg kg-1. While peach compost resulted in the lowest soil P levels, peach nano-black carbon yielded the highest soil P levels (21.6 mg kg-1). Comparing beneficial bacteria with PSB to Trichoderma (18.3 mg/kg-1), the former also shown an improvement in soil P (21.1 mg kg-1). Regarding P treatments, the application of 100 kg P per ha produced significantly higher soil P values (26.8 mg /kg-1), followed by 75 kg P per ha (18.3 mg /kg-1), and 50 kg P ha-1 produced the lowest soil P values (14.1 mg /kg-1). Comparing peach wastes and compost to peach nano-black carbon (13.7 g kg-1), SOC rose. In contrast to PSB (8.8 g kg-1), soil-treated Trichoderma was shown to have a greater SOC (11.1 g kg-1). Higher among the P levels.

Keywords: acidic stress, trichoderma, beneficial microbes, nano-black carbon, compost, peach residues, phosphorus, soybean

Procedia PDF Downloads 78
1966 Capsaicin Derivatives Enhanced Activity of α1β2γ2S-Aminobutyric Acid Type a Receptor Expressed in Xenopus laevis Oocytes

Authors: Jia H. Wong, Jingli Zhang, Habsah Mohamad, Iswatun H. Abdullah Ripain, Muhammad Bilal, Amelia J. Lloyd, Abdul A. Mohamed Yusoff, Jafri M. Abdullah

Abstract:

Epilepsy is one of the most common neurological diseases affecting more than 50 million of people worldwide. Epilepsy is a state of recurrent, spontaneous seizures with multiple syndromes and symptoms of different causes of brain dysfunction, prognosis, and treatments; characterized by transient, occasional and stereotyped interruptions of behavior whereby the excitatory-inhibitory activities within the central nervous system (CNS) are thrown out of balance due to various kinds of interferences. The goal of antiepileptic treatment is to enable patients to be free from seizures or to achieve control of seizures through surgical treatment and/or pharmacotherapy. Pharmacotherapy through AED plays an important role especially in countries with epilepsy treatment gap due to costs and availability of health facilities, skills and resources, yet there are about one-third of the people with epilepsy have drug-resistant seizures. Hence, this poses considerable challenges to the healthcare system and the effort in providing cost-effective treatment as well as the search for alternatives to treatment and management of epilepsy. Enhancement of γ-aminobutyric acid (GABA)-mediated inhibitory neurotransmission is one of the key mechanisms of actions of antiepileptic drugs. GABA type > a receptors (GABAAR) are ligand-gated ion channels that mediate rapid inhibitory neurotransmission upon the binding of GABA with a heteropentameric structure forming a central pore that is permeable to the influx of chloride ions in its activated state. The major isoform of GABAA receptors consists of two α1, two β2, and one γ2 subunit. It is the most abundantly expressed combinations in the brain and the most commonly researched through Xenopus laevis oocytes. With the advancing studies on ethnomedicine and traditional treatments using medicinal plants, increasing evidence reveal that spice and herb plants with medicinal properties play an important role in the treatment of ailments within communities across different cultures. Capsaicin is the primary natural capsaicinoid in hot peppers of plant genus Capsicum, consist of an aromatic ring, an amide linkage and a hydrophobic side chain. The study showed that capsaicins conferred neuroprotection in status epilepticus mouse models through anti-ictogenic, hypothermic, antioxidative, anti-inflammatory, and anti-apoptotic actions in a dose-dependent manner. In this study, five capsaicin derivatives were tested for their ability to increase the GABA-induced chloride current on α1β2γ2S of GABAAR expressed on Xenopus laevis oocytes using the method of two-microelectrode voltage clamp. Two of the capsaicin derivatives, IS5 (N-(4-hydroxy-3-methoxybenzyl)-3-methylbutyramide) and IS10 (N-(4-hydroxy-3-methoxybenzyl)-decanamide) at a concentration of 30µM were able to significantly increase the GABA-induced chloride current with p=0.002 and p=0.026 respectively. This study were able to show the enhancement effect of two capsaicin derivatives with moderate length of hydrocarbon chain on this receptor subtype, revealing the promising inhibitory activity of capsaicin derivatives through enhancement of GABA-induced chloride current and further investigations should be carried out to verify its antiepileptic effects in animal models.

Keywords: α1β2γ2 GABAA receptors, α1β2γ2S, antiepileptic, capsaicin derivatives, two-microelectrode voltage clamp, Xenopus laevis oocytes

Procedia PDF Downloads 362
1965 Spectral Anomaly Detection and Clustering in Radiological Search

Authors: Thomas L. McCullough, John D. Hague, Marylesa M. Howard, Matthew K. Kiser, Michael A. Mazur, Lance K. McLean, Johanna L. Turk

Abstract:

Radiological search and mapping depends on the successful recognition of anomalies in large data sets which contain varied and dynamic backgrounds. We present a new algorithmic approach for real-time anomaly detection which is resistant to common detector imperfections, avoids the limitations of a source template library and provides immediate, and easily interpretable, user feedback. This algorithm is based on a continuous wavelet transform for variance reduction and evaluates the deviation between a foreground measurement and a local background expectation using methods from linear algebra. We also present a technique for recognizing and visualizing spectrally similar clusters of data. This technique uses Laplacian Eigenmap Manifold Learning to perform dimensional reduction which preserves the geometric "closeness" of the data while maintaining sensitivity to outlying data. We illustrate the utility of both techniques on real-world data sets.

Keywords: radiological search, radiological mapping, radioactivity, radiation protection

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1964 Studying the Behavior of Asphalt Mix and Their Properties in the Presence of Nano Materials

Authors: Aman Patidar, Dipankar Sarkar, Manish Pal

Abstract:

Due to rapid development, increase in the traffic load, higher traffic volume and seasonal variation in temperature, asphalt pavement shows distresses like rutting, fatigue and thermal cracking etc. because of this pavement fails during service life so that bitumen needs to be modified with some additive. In this study VG30 grade bitumen modify with addition of nanosilica with 1% to 5% (increment of 1%) by weight of bitumen. Hot mix asphalt (HMA) have higher mixing, laying and rolling temperatures which leads to higher consumption of fuel. To address this issue, a nano material named ZycoTherm which is chemical warm mix asphalt (WMA) additive is added to bitumen. Nanosilica modification (NSMB) results in the increase in stability compared to unmodified bitumen (UMB). WMA modified mix shows slightly higher stability than UMB and NSMB in a lower bitumen content. The Retained stability and tensile strength ratio (TSR) is more than 75% and 80% respectively for both mixes. Nanosilica with WMA has more resistant to temperature susceptibility, moisture susceptibility and short term aging than NSMB.

Keywords: HMA, nanosilica, NSMB, temperature, TSR, UMB, WMA

Procedia PDF Downloads 311
1963 Theoretical Study of Carbonic Anhydrase-Ii Inhibitors for Treatment of Glaucoma

Authors: F. Boukli Hacene, W. Soufi, S. Ghalem

Abstract:

Glaucoma disease is a progressive degenerative optic neuropathy, with irreversible visual field deficits and high eye pressure being one of the risk factors. Sulfonamides are carbonic anhydrase-II inhibitors that aim to decrease the secretion of aqueous humor by direct inhibition of this enzyme at the level of the ciliary processes. These drugs present undesirable effects that are difficult to accept by the patient. In our study, we are interested in the inhibition of carbonic anhydrase-II by different natural ligands (curcumin analogues) using molecular modeling methods using molecular operating environment (MOE) software to predict their interaction with this enzyme.

Keywords: carbonic anhydrase-II, curcumin analogues, drug research, molecular modeling

Procedia PDF Downloads 89
1962 Bioactivities and Phytochemical Studies of Acrocarpus fraxinifolius Bark Wight and Arn

Authors: H. M. El-Rafie, A. H. Abou Zeid, R. S. Mohammed, A. A. Sleem

Abstract:

Acrocarpus is a genus of flowering plants in the legume family Fabaceae which considered as a large and economically important family. This study aimed to investigate the phytoconstituents of the petroleum ether extract (PEE) of Acrocarpus fraxinofolius bark by Gas chromatography coupled with mass spectrometry (GC/MS) analysis of its fractions (fatty acid and unsaponifiable matter). Concerning this, identification of 52 compounds constituting 97.03 % of the total composition of the unsaponifiable matter fraction. Cycloeucalenol was found to be the major compound representing 32.52% followed by 4a, 14a-dimethyl-A8~24(28)-ergostadien (26.50%) and ß-sitosterol(13.74%), furthermore Gas liquid chromatography (GLC) analysis of the sterol fraction revealed the identification of cholesterol (7.22 %), campesterol (13.30 %), stigmasterol (10.00 %) and β - sitosterol (69.48 %). Meanwhile, the identification of 33 fatty acids representing 90.71% of the total fatty acid constituents. Methyl-9,12-octadecadienoate (40.39%) followed by methyl hexadecanoate (23.64%) were found to be the major compounds. On the other hand, column chromatography and Thin layer chromatography (TLC) fractionation of PEE separate the triterpenoid: 21β-hydroxylup-20(29)-en-3-one and β- amyrin which were structurally identified by spectroscopic analysis (NMR, MS and IR). PEE has been biologically evaluated for 1: management of diabetes in alloxan induced diabetic rats 2: cytotoxic activity against four human tumor cell lines (Cervix carcinoma cell line[HELA], Breast carcinoma cell line [MCF7], Liver carcinoma cell line[HEPG2] and Colon carcinoma cell line[HCT-116] 3: hepatoprotective activity against CCl4-induced hepatotoxicity in rats and the activity was studied by assaying the serum marker enzymes like AST, ALT, and ALP. Concerning this, the anti-diabetic activity exhibited by 100mg of PEE extract was 74.38% relative to metformin (100% potency). It also showed a significant anti-proliferative activity against MCF-7 (IC50= 2.35µg), Hela(IC50=3.85µg) and HEPG-2 (IC50= 9.54µg) compared with Doxorubicin as reference drug. The hepatoprotective activity was evidenced by significant decrease in liver function enzymes, i.e. AST, ALT and ALP by (29.18%, 28.26%, and 34.11%, respectively using silymarin as the reference drug, compared to their concentration levels in an untreated group with liver damage induced by CCl₄. This study was performed for the first time on the bark of this species.

Keywords: Acrocarpus fraxinofolius, antidiabetic, cytotoxic, hepatoprotective

Procedia PDF Downloads 196
1961 Nano Gold and Silver for Control of Mosquitoes Manipulating Nanogeometries

Authors: Soam Prakash, Namita Soni

Abstract:

The synthesis of metallic nanoparticles is an active area of academic and more significantly, applied research in nanotechnology. Currently, nanoparticle research is an area of intense scientific interest. Silver (Ag) and Gold (Au) nanoparticles (NPs) have been the focus of fungi and plant based syntheses. Silver and gold nanoparticles are nanoparticles of silver and gold. These particles are of between 1 nm and 100 nm in size. Silver and gold have been use in the wide variety of potential applications in biomedical, optical, electronic field, treatment of burns, wounds, and several bacterial infections. There is a crucial need to produce new insecticides due to resistance and high-cost of organic insecticides which are more environmentally-friendly, safe, and target-specific. Synthesizing nanoparticles using plants and microorganisms can eliminate this problem by making the nanoparticles more biocompatible. Here we reviewed the mosquitocidal and antimicrobials activity of silver and gold nanoparticles using fungi, plants as well as bacteria.

Keywords: nano gold, nano silver, Malaria, Chikengunia, dengue control

Procedia PDF Downloads 436
1960 Bioactivity of Local Isolated Probiotic to Inhibiting Important Bacterial Pathogens in Aquaculture

Authors: Abhichet Nobhiwong, Jiraporn Rojtinnakorn, Udomluk Sompong

Abstract:

Six probiotic strains isolated from Chiang Mai and Chiang Rai province, Thailand; CR1-2, CM3-4, CM5-2, CR7-8, CM10-5 and CM10-8 were used to study their morphology and inhibition activity on three pathogenic bacteria; Aeromonas sp., Streptococcus sp. and Flavobacterium sp. that isolated from infected Nile tilapia. The agar well diffusion technique was applied for 24 and 48 hours incubation. Interestingly, some probiotics showed good inhibition activity both 24 and 48 hours on each 3 bacterial pathogens. The capable inhibiting Aeromonas sp. were CR1-2 and CR5-2 with inhibition diameters of 13.0 mm and 11.2 mm, respectively. For Streptococcus sp., effective probiotics were CR10-2 with inhibition diameters of 10.7 mm. Whereas for Flavobacterium sp., effective probiotics were CR5-2 with inhibition diameter of 9.7 mm. It can be concluded that these probiotics have potentiality to develop as the pathogens biocontrol products. These will be support for safety and organic aquaculture that which the most worthy for people health.

Keywords: probiotics, Aeromanas sp., Streptococcus sp., Flavobacterium sp.

Procedia PDF Downloads 273
1959 Universe at Zero Second and the Creation Process of the First Particle from the Absolute Void

Authors: Shivan Sirdy

Abstract:

In this study, we discuss the properties of absolute void space or the universe at zero seconds, and how these properties play a vital role in creating a mechanism in which the very first particle gets created simultaneously everywhere. We find the limit in which when the absolute void volume reaches will lead to the collapse that leads to the creation of the first particle. This discussion is made following the elementary dimensions theory study that was peer-reviewed at the end of 2020; everything in the universe is made from four elementary dimensions, these dimensions are the three spatial dimensions (X, Y, and Z) and the Void resistance as the factor of change among the four. Time itself was not considered as the fourth dimension. Rather time corresponds to a factor of change, and during the research, it was found out that the Void resistance is the factor of change in the absolute Void space, where time is a hypothetical concept that represents changes during certain events compared to a constant change rate event. Therefore, time does exist, but as a factor of change as the Void resistance: Time= factor of change= Void resistance.

Keywords: elementary dimensions, absolute void, time alternative, early universe, universe at zero second, Void resistant, Hydrogen atom, Hadron field, Lepton field

Procedia PDF Downloads 202
1958 Effect of Nickel Coating on Corrosion of Alloys in Molten Salts

Authors: Divya Raghunandanan, Bhavesh D. Gajbhiye, C. S. Sona, Channamallikarjun S. Mathpati

Abstract:

Molten fluoride salts are considered as potential coolants for next generation nuclear plants where the heat can be utilized for production of hydrogen and electricity. Among molten fluoride salts, FLiNaK (LiF-NaF-KF: 46.5-11.5-42 mol %) is a potential candidate for the coolant due to its superior thermophysical properties such as high temperature stability, boiling point, volumetric heat capacity and thermal conductivity. Major technical challenge in implementation is the selection of structural material which can withstand corrosive nature of FLiNaK. Corrosion study of alloys SS 316L, Hastelloy B, Ni-201 was performed in molten FLiNaK at 650°C. Nickel was found to be more resistant to corrosive attack in molten fluoride medium. Corrosion experiments were performed to study the effect of nickel coating on corrosion of alloys SS 316L and Hastelloy B. Weight loss of the alloys due to corrosion was measured and corrosion rate was estimated. The surface morphology of the alloys was analyzed by Scanning Electron Microscopy.

Keywords: corrosion, FLiNaK, hastelloy, weight loss

Procedia PDF Downloads 441
1957 Phytochemical Screening and Assessment of Hepatoprotective Activity of Geigeria alata Leaves Ethanolic Extract on Wistar Rats

Authors: Girgis Younan, Ikram Eltayeb

Abstract:

Geigeria alata belongs to the family Asteraceae, is an effective plant traditionally used in Sudan as a therapy for hepatic disease and as an antiepileptic, antispasmodic and to treat cough and intestinal complaints.The liver is responsible for many critical functions within the body and any liver disease or injury will result in the loss of those functions leading to significant damage in the body. Liver diseases cause increase in liver enzymes (AST, ALP ALT) and total bilirubin and a decrease in total blood protein level. The objective of this study is to investigate the hepato-protective activity of Geigeria alata leaves ethanolic extract. The plant leaves were extracted using 96% ethanol using Soxhlet apparatus. The hepatoprotective effect was determined using 25 wistar rats, the rats was divided to 5 groups, each group contain 5 rats: [Normal control group] receiving purified water, liver damage was induced in wistar rats by administering a 1:1 (v/v) mixture of CCl4 (1.25 ml/kg) and olive oil once at day four of the experiment [negative control group]. Two doses of extract [400mg/kg and 200mg/kg] was applied daily for 7 days, and standard drug Silymarin (200 mg/kg) were administered daily for 7 days to CCl4-treated rats. The degree of hepato-protective activity was evaluated by determining the hepatic marker enzymes AST, ALP, ALT, total Bilirubin and total proteins (TP). Results have shown that, the extract of G.alata leaves reduced the level of liver enzymes ALT, AST, ALP, total bilirubin and increased the level of total proteins. Since the levels of liver enzymes; bilirubin and total protein are considered as markers of liver function, the extract has proven to reduce the detrimental effects of liver toxicity induced using CCl4. The hepato-protective effect of extract on liver was found to be dose dependent, where the 400mg/kg dose of the extract exhibited higher activity than 200mg/kg dose. In addition, the effect of the higher dose (400mg/kg) of the extract was found to be higher than Silymarin standard drug. The result concludes that, G.alata leaves extract was found to exhibit profound hepato-protective activity, which justifies the traditional use of the plant for the treatment of hepatic diseases.

Keywords: alata, extract, geigeria, hepatoprotective

Procedia PDF Downloads 233
1956 Fermentation of Tolypocladium inflatum to Produce Cyclosporin in Dairy Waste Culture Medium

Authors: Fereshteh Falah, Alireza Vasiee, Farideh Tabatabaei-Yazdi

Abstract:

In this research, we investigated the usage of dairy sludge in the fermentation process and cyclosporin production. This bioactive compound is a metabolite produced by Tolypocladium inflatum. Results showed that about 200 ppm of cyclosporin can be produced in this fermentation. In order to have a proper and specific function, CyA must be free of any impurities, so we need purification. In this downstream processing, we used chromatographic extraction and evaluation of pharmacological activities of cyA. Results showed that the obtained metabolite has very high activity against Aspergilus niger (25mm clear zone). This cyclosporin was isolated for use as an antibiotic. The current research shows that this drug is very vital and commercially very important.

Keywords: fermentation, cyclosporin A, Tolypocladium inflatum, TLC

Procedia PDF Downloads 127
1955 Effects of Nanoencapsulated Echinacea purpurea Ethanol Extract on the Male Reproductive Function in Streptozotocin-Induced Diabetic Rats

Authors: Jia-Ling Ho, Xiu-Ru Zhang, Zwe-Ling Kong

Abstract:

Diabetes mellitus (DM) is a major health problem that affects patients’ life quality throughout the world due to its many complications. It characterized by chronic hyperglycemia with oxidative stress, which impaired male reproductive function. Fibroblast growth factor 21 (FGF21) is a metabolic regulator that is required for normal spermatogenesis and protects against diabetes-induced germ cell apoptosis. Echinacea purpurea ethanol extract (EE), which contain phenolic acid and isobutylamide, had been proven to have antidiabetic property. Silica-chitosan nanoparticles (Nano-CS) has drug delivery and controlled release properties. This study aims to investigate whether silica-chitosan nanoparticles encapsulated EE (Nano-EE) had more ameliorating male infertility by analyzing the effect of testicular FGF21. The Nano-EE was characterized before used to treatment the diabetic rat model. Male Sprague-Dawley (SD) rats were obtained and divided into seven groups. A group was no induced Streptozotocin (STZ), marked as normal group. Diabetic rats were induced into diabetes by STZ (33 mg/kg). A diabetic group was no treatment with sample (diabetic control group), and other groups were treatment by Nano-CS (465 mg/kg), Nano-EE (93, 279, 465 mg/kg), and metformin (Met) (200 mg/kg) used as reference drug for 7 weeks. Our results indicated that the average nanoparticle size and zeta potential of Nano-EE were 2630 nm and -21.3 mV, respectively. The encapsulation ratio of Nano-EE was about 70%. It also confirmed the antioxidative activity was unchanged by comparing the DPPH and ABTS scavenging of Nano-EE and EE. In vivo test, Nano-EE can improve the STZ induced hyperglycemia, insulin resistance, and plasma FGF21 levels. Nano-EE has increased sperm motility, mitochondria membrane potential (MMP), plasma testosterone level, and reduction of abnormal sperm, nitric oxide (NO), superoxide production as well as reactive oxygen species (ROS). In addition, in plasma antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD) was increased whereas pro-inflammatory cytokines TNF-α, and IL-1β were decreased. Further, in testis, protein content of FGF21, PGC-1α, and SIRT1 were improved. Nano-EE might improve diabetes-induced down-regulation of testicular FGF21 and SIRT1/PGC-1α signaling hence maintain spermatogenesis.

Keywords: diabetes mellitus, Echinacea purpurea, reproductive dysfunction, silica-chitosan nanoparticles

Procedia PDF Downloads 192
1954 An Effective Noise Resistant Frequency Modulation Continuous-Wave Radar Vital Sign Signal Detection Method

Authors: Lu Yang, Meiyang Song, Xiang Yu, Wenhao Zhou, Chuntao Feng

Abstract:

To address the problem that the FM continuous-wave radar (FMCW) extracts human vital sign signals which are susceptible to noise interference and low reconstruction accuracy, a new detection scheme for the sign signals is proposed. Firstly, an improved complete ensemble empirical modal decomposition with adaptive noise (ICEEMDAN) algorithm is applied to decompose the radar-extracted thoracic signals to obtain several intrinsic modal functions (IMF) with different spatial scales, and then the IMF components are optimized by a BP neural network improved by immune genetic algorithm (IGA). The simulation results show that this scheme can effectively separate the noise and accurately extract the respiratory and heartbeat signals and improve the reconstruction accuracy and signal-to-noise ratio of the sign signals.

Keywords: frequency modulated continuous wave radar, ICEEMDAN, BP neural network, vital signs signal

Procedia PDF Downloads 166
1953 Effect of Radioprotectors on DNA Repair Enzyme and Survival of Gamma-Irradiated Cell Division Cycle Mutants of Saccharomyces pombe

Authors: Purva Nemavarkar, Badri Narain Pandey, Jitendra Kumar

Abstract:

Introduction: The objective was to understand the effect of various radioprotectors on DNA damage repair enzyme and survival in gamma-irradiated wild and cdc mutants of S. pombe (fission yeast) cultured under permissive and restrictive conditions. DNA repair process, as influenced by radioprotectors, was measured by activity of DNA polymerase in the cells. The use of single cell gel electrophoresis assay (SCGE) or Comet Assay to follow gamma-irradiation induced DNA damage and effect of radioprotectors was employed. In addition, studying the effect of caffeine at different concentrations on S-phase of cell cycle was also delineated. Materials and Methods: S. pombe cells grown at permissive temperature (250C) and/or restrictive temperature (360C) were followed by gamma-radiation. Percentage survival and activity of DNA Polymerase (yPol II) were determined after post-irradiation incubation (5 h) with radioprotectors such as Caffeine, Curcumin, Disulphiram, and Ellagic acid (the dose depending on individual D 37 values). The gamma-irradiated yeast cells (with and without the radioprotectors) were spheroplasted by enzyme glusulase and subjected to electrophoresis. Radio-resistant cells were obtained by arresting cells in S-phase using transient treatment of hydroxyurea (HU) and studying the effect of caffeine at different concentrations on S-phase of cell cycle. Results: The mutants of S. pombe showed insignificant difference in survival when grown under permissive conditions. However, growth of these cells under restrictive temperature leads to arrest in specific phases of cell cycle in different cdc mutants (cdc10: G1 arrest, cdc22: early S arrest, cdc17: late S arrest, cdc25: G2 arrest). All the cdc mutants showed decrease in survival after gamma radiation when grown at permissive and restrictive temperatures. Inclusion of the radioprotectors at respective concentrations during post irradiation incubation showed increase in survival of cells. Activity of DNA polymerase enzyme (yPol II) was increased significantly in cdc mutant cells exposed to gamma-radiation. Following SCGE, a linear relationship was observed between doses of irradiation and the tail moments of comets. The radioprotection of the fission yeast by radioprotectors can be seen by the reduced tail moments of the yeast comets. Caffeine also exhibited its radio-protective ability in radio-resistant S-phase cells obtained after HU treatment. Conclusions: The radioprotectors offered notable radioprotection in cdc mutants when added during irradiation. The present study showed activation of DNA damage repair enzyme (yPol II) and an increase in survival after treatment of radioprotectors in gamma irradiated wild type and cdc mutants of S. pombe cells. Results presented here showed feasibility of applying SCGE in fission yeast to follow DNA damage and radioprotection at high doses, which are not feasible with other eukaryotes. Inclusion of caffeine at 1mM concentration to S phase cells offered protection and did not decrease the cell viability. It can be proved that at minimal concentration, caffeine offered marked radioprotection.

Keywords: radiation protection, cell cycle, fission yeast, comet assay, s-phase, DNA repair, radioprotectors, caffeine, curcumin, SCGE

Procedia PDF Downloads 113
1952 Temperature Distribution Control for Baby Incubator System Using Arduino AT Mega 2560

Authors: W. Widhiada, D. N. K. P. Negara, P. A. Suryawan

Abstract:

The technological advances in the field of health to be very important, especially on the safety of the baby. In this case a lot of premature infants death caused by poorly managed health facilities. Mostly the death of premature baby caused by bacteria since the temperature around the baby is not normal. Related to this, the incubator equipment needs to be important, especially in how to control the temperature in incubator. On/Off controls is used to regulate the temperature distribution in the incubator so that the desired temperature is 36 °C to stay awake and stable. The authors have been observed and analyzed the data to determine the temperature distribution in the incubator using program of MATLAB/Simulink. The output temperature distribution is obtained at 36 °C in 400 seconds using an Arduino AT 2560. This incubator is able to maintain an ambient temperature and maintain the baby's body temperature within normal limits and keep the moisture in the air in accordance with the limit values required in infant incubator.

Keywords: on/off control, distribution temperature, Arduino AT 2560, baby incubator

Procedia PDF Downloads 502
1951 Prevalence of Cyp2d6 and Its Implications for Personalized Medicine in Saudi Arabs

Authors: Hamsa T. Tayeb, Mohammad A. Arafah, Dana M. Bakheet, Duaa M. Khalaf, Agnieszka Tarnoska, Nduna Dzimiri

Abstract:

Background: CYP2D6 is a member of the cytochrome P450 mixed-function oxidase system. The enzyme is responsible for the metabolism and elimination of approximately 25% of clinically used drugs, especially in breast cancer and psychiatric therapy. Different phenotypes have been described displaying alleles that lead to a complete loss of enzyme activity, reduced function (poor metabolizers – PM), hyperfunctionality (ultrarapid metabolizers–UM) and therefore drug intoxication or loss of drug effect. The prevalence of these variants may vary among different ethnic groups. Furthermore, the xTAG system has been developed to categorized all patients into different groups based on their CYP2D6 substrate metabolization. Aim of the study: To determine the prevalence of the different CYP2D6 variants in our population, and to evaluate their clinical relevance in personalized medicine. Methodology: We used the Luminex xMAP genotyping system to sequence 305 Saudi individuals visiting the Blood Bank of our Institution and determine which polymorphisms of CYP2D6 gene are prevalent in our region. Results: xTAG genotyping showed that 36.72% (112 out of 305 individuals) carried the CYP2D6_*2. Out of the 112 individuals with the *2 SNP, 6.23% had multiple copies of *2 SNP (19 individuals out of 305 individuals), resulting in an UM phenotype. About 33.44% carried the CYP2D6_*41, which leads to decreased activity of the CYP2D6 enzyme. 19.67% had the wild-type alleles and thus had normal enzyme function. Furthermore, 15.74% carried the CYP2D6_*4, which is the most common nonfunctional form of the CYP2D6 enzyme worldwide. 6.56% carried the CYP2D6_*17, resulting in decreased enzyme activity. Approximately 5.73% carried the CYP2D6_*10, consequently decreasing the enzyme activity, resulting in a PM phenotype. 2.30% carried the CYP2D6_*29, leading to decreased metabolic activity of the enzyme, and 2.30% carried the CYP2D6_*35, resulting in an UM phenotype, 1.64% had a whole-gene deletion CYP2D6_*5, thus resulting in the loss of CYP2D6 enzyme production, 0.66% carried the CYP2D6_*6 variant. One individual carried the CYP2D6_*3(B), producing an inactive form of the enzyme, which leads to decrease of enzyme activity, resulting in a PM phenotype. Finally, one individual carried the CYP2D6_*9, which decreases the enzyme activity. Conclusions: Our study demonstrates that different CYP2D6 variants are highly prevalent in ethnic Saudi Arabs. This finding sets a basis for informed genotyping for these variants in personalized medicine. The study also suggests that xTAG is an appropriate procedure for genotyping the CYP2D6 variants in personalized medicine.

Keywords: CYP2D6, hormonal breast cancer, pharmacogenetics, polymorphism, psychiatric treatment, Saudi population

Procedia PDF Downloads 572