Search results for: induced pulsation
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2716

Search results for: induced pulsation

2416 Suppression of Immunostimulatory Function of Dendritic Cells and Prolongation of Skin Allograft Survival by Dryocrassin

Authors: Hsin-Lien Lin, Ju-Hui Fu

Abstract:

Dendritic cells (DCs) are the major professional antigen-presenting cells for the development of optimal T-cell immunity. DCs can be used as pharmacological targets to screen novel biological modifiers for the treatment of harmful immune responses, such as transplantation rejection. Dryopteris crassirhizoma Nakai (Aspiadaceae) is used for traditional herbal medicine in the region of East Asia. The root of this fern plant has been listed for treating inflammatory diseases. Dryocrassin is the tetrameric phlorophenone component derived from Dryopteris. Here, we tested the immunomodulatory potential of dryocrassin on lipopolysaccharide (LPS)-stimulated activation of mouse bone marrow-derived DCs in vitro and in skin allograft transplantation in vivo. Results demonstrated that dryocrassin reduced the secretion of tumor necrosis factor-α, interleukin-6, and interleukin-12p70 by LPS-stimulated DCs. The expression of LPS-induced major histocompatibility complex class II, CD40, and CD86 on DCs was also blocked by dryocrassin. Moreover, LPS-stimulated DC-elicited allogeneic T-cell proliferation was lessened by dryocrassin. In addition, dryocrassin inhibited LPS-induced activation of IϰB kinase, JNK/p38 mitogen-activated protein kinase, as well as the translocation of NF-ϰB. Treatment with dryocrassin obviously diminished 2,4-dinitro-1-fluorobenzene- induced delayed-type hypersensitivity and prolonged skin allograft survival. Dryocrassin may be one of the potent immunosuppressive agents for transplant rejection through the destruction of DC maturation and function.

Keywords: dryocrassin, dendritic cells, immunosuppression, skin allograft

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2415 Amniotic Fluid Stem Cells Ameliorate Cisplatin-Induced Acute Renal Failure through Autophagy Induction and Inhibition of Apoptosis

Authors: Soniya Nityanand, Ekta Minocha, Manali Jain, Rohit Anthony Sinha, Chandra Prakash Chaturvedi

Abstract:

Amniotic fluid stem cells (AFSC) have been shown to contribute towards the amelioration of Acute Renal Failure (ARF), but the mechanisms underlying the renoprotective effect are largely unknown. Therefore, the main goal of the current study was to evaluate the therapeutic efficacy of AFSC in a cisplatin-induced rat model of ARF and to investigate the underlying mechanisms responsible for its renoprotective effect. To study the therapeutic efficacy of AFSC, ARF was induced in Wistar rats by an intra-peritoneal injection of cisplatin, and five days after administration, the rats were randomized into two groups and injected with either AFSC or normal saline intravenously. On day 8 and 12 after cisplatin injection, i.e., day 3 and day7 post-therapy respectively, the blood biochemical parameters, histopathological changes, apoptosis and expression of pro-apoptotic, anti-apoptotic and autophagy-related proteins in renal tissues were studied in both groups of rats. Administration of AFSC in ARF rats resulted in improvement of renal function and attenuation of renal damage as reflected by significant decrease in blood urea nitrogen, serum creatinine levels, tubular cell apoptosis as assessed by Bax/Bcl2 ratio, and expression of the pro-apoptotic proteins viz. PUMA, Bax, cleaved caspase-3 and cleaved caspase-9 as compared to saline-treated group. Furthermore, in the AFSC-treated group as compared to saline-treated group, there was a significant increase in the activation of autophagy as evident by increased expression of LC3-II, ATG5, ATG7, Beclin1 and phospho-AMPK levels with a concomitant decrease in phospho-p70S6K and p62 expression levels. To further confirm whether the protective effects of AFSC on cisplatin-induced apoptosis were dependent on autophagy, chloroquine, an autophagy inhibitor was administered by the intra-peritoneal route. Chloroquine administration led to significant reduction in the anti-apoptotic effects of the AFSC therapy and further deterioration in the renal structure and function caused by cisplatin. Collectively, our results put forth that AFSC ameliorates cisplatin-induced ARF through induction of autophagy and inhibition of apoptosis. Furthermore, the protective effects of AFSC were blunted by chloroquine, highlighting that activation of autophagy is an important mechanism of action for the protective role of AFSC in cisplatin-induced renal injury.

Keywords: amniotic fluid stem cells, acute renal failure, autophagy, cisplatin

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2414 Mango (Mangifera indica L.) Lyophilization Using Vacuum-Induced Freezing

Authors: Natalia A. Salazar, Erika K. Méndez, Catalina Álvarez, Carlos E. Orrego

Abstract:

Lyophilization, also called freeze-drying, is an important dehydration technique mainly used for pharmaceuticals. Food industry also uses lyophilization when it is important to retain most of the nutritional quality, taste, shape and size of dried products and to extend their shelf life. Vacuum-Induced during freezing cycle (VI) has been used in order to control ice nucleation and, consequently, to reduce the time of primary drying cycle of pharmaceuticals preserving quality properties of the final product. This procedure has not been applied in freeze drying of foods. The present work aims to investigate the effect of VI on the lyophilization drying time, final moisture content, density and reconstitutional properties of mango (Mangifera indica L.) slices (MS) and mango pulp-maltodextrin dispersions (MPM) (30% concentration of total solids). Control samples were run at each freezing rate without using induced vacuum. The lyophilization endpoint was the same for all treatments (constant difference between capacitance and Pirani vacuum gauges). From the experimental results it can be concluded that at the high freezing rate (0.4°C/min) reduced the overall process time up to 30% comparing process time required for the control and VI of the lower freeze rate (0.1°C/min) without affecting the quality characteristics of the dried product, which yields a reduction in costs and energy consumption for MS and MPM freeze drying. Controls and samples treated with VI at freezing rate of 0.4°C/min in MS showed similar results in moisture and density parameters. Furthermore, results from MPM dispersion showed favorable values when VI was applied because dried product with low moisture content and low density was obtained at shorter process time compared with the control. There were not found significant differences between reconstitutional properties (rehydration for MS and solubility for MPM) of freeze dried mango resulting from controls, and VI treatments.

Keywords: drying time, lyophilization, mango, vacuum induced freezing

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2413 Development of Cationic Gelatin Nanoparticles as an Antigen-Carrier for Mucosal Immunization

Authors: Ping-Lun Jiang, Hung-Jun Lin, Shen-Fu Lin, Mei-Yin Chien, Ting-Wei Li, Chun-Han Lin, Der-Zen Liu

Abstract:

Mucosal vaccine induces both mucosal (secretory IgA) and systemic immune responses and it is considered an ideal vaccination strategy for prevention of infectious diseases. One important point to be considered in mucosal vaccination is effective antigen delivery system which can manage effective delivery of antigen to antigen-presenting cells (APCs) of mucosal. In the present study, cationic gelatin nanoparticles were prepared as ideal carriers for more efficient antigen delivery. The average diameter of cationic gelatin nanoparticle was approximate 190 nm, and the zeta potential was about +45 mV, then ovalbumin (OVA) was physically absorbed onto cationic gelatin nanoparticle. The OVA absorption rate was near 95% the zeta potential was about +20 mV. We show that cationic gelatin nanoparticle effectively facilitated antigen uptake by mice bone marrow-derived dendritic cells (mBMDCs) and RAW264.7 cells and induced higher levels of pro-inflammatory cytokines. C57BL/6 mice twice immunized intranasally with OVA-absorbed cationic gelatin nanoparticle induced high levels of OVA-specific IgG in the serum and IgA in their in the nasal and lung wash fluid. These results indicate that nasal administration of cationic gelatin nanoparticles induced both mucosal and systemic immune responses and cationic gelatin nanoparticles might be a potential antigen delivery carrier for further clinical applications.

Keywords: antigen delivery, antigen-presenting cells, gelatin nanoparticle, mucosal vaccine

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2412 Zingiberofficinale Potential Effect on Nephrin mRNA Expression in Cisplatin Induced Nephrotoxicity

Authors: Nadia A. Mohamed, Mehrevan M. Abdel-Moniem

Abstract:

Zingiber officinale (ginger) has been cultivated for medicinal purposes due to their various proprieties both in vitro and in vivo, so we designed to evaluate the ginger’s potential effect on nephrin m RNA expression in cisplatin-induced nephrotoxic rats. Method: Forty male albino rats were divided into group I was injected (IP) with one ml saline, group II(cisplatin) injected (IP) with a single dose of 12 mg/kg cisplatin, group III (ginger) received (PO) 310 mg/kg for 30 successive days, and group IV(cisplatin and ginger) rats received ginger extract (310 mg/kg) daily for 20 successive days (PO), and then on day 20 of ginger extract administration each rat was injected(IP) with a single dose of 12 mg/kg cisplatin. The blood was sampled to assess urea, creatinine (SC), while the levels of malondialdehyde (MDA), nitric oxide (NO) and paraoxonase (PON1) were measured in kidney tissue homogenate. Expression of urinary nephrin gene (nephrin mRNA) was detected using qRT-PCR. Results: Treatment with ginger significantly decreased the levels of kidney function parameters as well as MDA and NO elevated by cisplatin injection, while PON1 was significantly reduced in the cisplatin group. However, the protection of male rats with ginger significantly increased the levels of nephrin gene expression and PON1 compared with the cisplatin-treated group. Our results generated a proposal on the ameliorating effect of ginger on nephrin mRNA gene expression reduction in cisplatin-induced nephrotoxicity.

Keywords: nephrin mRNA, ginger, cisplatin, nephrotoxicity

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2411 Oxygen Transport in Blood Flows Pasts Staggered Fiber Arrays: A Computational Fluid Dynamics Study of an Oxygenator in Artificial Lung

Authors: Yu-Chen Hsu, Kuang C. Lin

Abstract:

The artificial lung called extracorporeal membrane oxygenation (ECMO) is an important medical machine that supports persons whose heart and lungs dysfunction. Previously, investigation of steady deoxygenated blood flows passing through hollow fibers for oxygen transport was carried out experimentally and computationally. The present study computationally analyzes the effect of biological pulsatile flow on the oxygen transport in blood. A 2-D model with a pulsatile flow condition is employed. The power law model is used to describe the non-Newtonian flow and the Hill equation is utilized to simulate the oxygen saturation of hemoglobin. The dimensionless parameters for the physical model include Reynolds numbers (Re), Womersley parameters (α), pulsation amplitudes (A), Sherwood number (Sh) and Schmidt number (Sc). The present model with steady-state flow conditions is well validated against previous experiment and simulations. It is observed that pulsating flow amplitudes significantly influence the velocity profile, pressure of oxygen (PO2), saturation of oxygen (SO2) and the oxygen mass transfer rates (m ̇_O2). In comparison between steady-state and pulsating flows, our findings suggest that the consideration of pulsating flow in the computational model is needed when Re is raised from 2 to 10 in a typical range for flow in artificial lung.

Keywords: artificial lung, oxygen transport, non-Newtonian flows, pulsating flows

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2410 Protective Role of Fish Oil against Hepatotoxicity Induced by Fipronil on Female Rats

Authors: Amel A. Refaie, Amal Ramadan, Abdel-Tawab H. Mossa

Abstract:

This study was designed to evaluate the adverse effects of sub-chronic exposure to the fipronil on the liver of female rats at a dose equal to 400 mg /kg (1/10LD50) in drinking water and the protective role of fish oil at concentration 117.6 mg/Kg b.wt via oral routes daily for 28 days. Fipronil treatment caused a decrease in body weight gain and increase in relative liver weight. Fipronil induced a significant increase in the liver biomarkers enzymes such as alanine aminotransferases (ALT), aspartate aminotransferases (AST), alkaline phosphatase (ALP) and levels of total protein while fipronil caused a significant decrease in butyryl cholinesterase activity in FPN-treated rats. Oxidative stress biomarkers such as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST) were significantly decreased in liver tissue, while lipid peroxidation (LPO) was significantly increased in fipronil treating rats in a dose-dependent manner. FPN caused histopathological alterations in liver of female rats. From our results, it can be reported that FPN induced lipid peroxidation, oxidative stress, liver injury in female rats and fish oil used to protect animals against the adverse effect of pesticide exposure. These pathophysiological alterations in liver tissues could be due to the toxic effect of fipronil that associated with a generation of free radicals.

Keywords: fipronil (FPN), fish oil, hepatotoxicity, transaminases, antioxidant enzymes, female rats

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2409 Mapping Man-Induced Soil Degradation in Armenia's High Mountain Pastures through Remote Sensing Methods: A Case Study

Authors: A. Saghatelyan, Sh. Asmaryan, G. Tepanosyan, V. Muradyan

Abstract:

One of major concern to Armenia has been soil degradation emerged as a result of unsustainable management and use of grasslands, this in turn largely impacting environment, agriculture and finally human health. Hence, assessment of soil degradation is an essential and urgent objective set out to measure its possible consequences and develop a potential management strategy. Since recently, an essential tool for assessing pasture degradation has been remote sensing (RS) technologies. This research was done with an intention to measure preciseness of Linear spectral unmixing (LSU) and NDVI-SMA methods to estimate soil surface components related to degradation (fractional vegetation cover-FVC, bare soils fractions, surface rock cover) and determine appropriateness of these methods for mapping man-induced soil degradation in high mountain pastures. Taking into consideration a spatially complex and heterogeneous biogeophysical structure of the studied site, we used high resolution multispectral QuickBird imagery of a pasture site in one of Armenia’s rural communities - Nerkin Sasoonashen. The accuracy assessment was done by comparing between the land cover abundance data derived through RS methods and the ground truth land cover abundance data. A significant regression was established between ground truth FVC estimate and both NDVI-LSU and LSU - produced vegetation abundance data (R2=0.636, R2=0.625, respectively). For bare soil fractions linear regression produced a general coefficient of determination R2=0.708. Because of poor spectral resolution of the QuickBird imagery LSU failed with assessment of surface rock abundance (R2=0.015). It has been well documented by this particular research, that reduction in vegetation cover runs in parallel with increase in man-induced soil degradation, whereas in the absence of man-induced soil degradation a bare soil fraction does not exceed a certain level. The outcomes show that the proposed method of man-induced soil degradation assessment through FVC, bare soil fractions and field data adequately reflects the current status of soil degradation throughout the studied pasture site and may be employed as an alternate of more complicated models for soil degradation assessment.

Keywords: Armenia, linear spectral unmixing, remote sensing, soil degradation

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2408 Damage Assessment Based on Full-Polarimetric Decompositions in the 2017 Colombia Landslide

Authors: Hyeongju Jeon, Yonghyun Kim, Yongil Kim

Abstract:

Synthetic Aperture Radar (SAR) is an effective tool for damage assessment induced by disasters due to its all-weather and night/day acquisition capability. In this paper, the 2017 Colombia landslide was observed using full-polarimetric ALOS/PALSAR-2 data. Polarimetric decompositions, including the Freeman-Durden decomposition and the Cloude decomposition, are utilized to analyze the scattering mechanisms changes before and after-landslide. These analyses are used to detect the damaged areas induced by the landslide. Experimental results validate the efficiency of the full polarimetric SAR data since the damaged areas can be well discriminated. Thus, we can conclude the proposed method using full polarimetric data has great potential for damage assessment of landslides.

Keywords: Synthetic Aperture Radar (SAR), polarimetric decomposition, damage assessment, landslide

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2407 Curative Effect of Blumea lacera Leaves on Experimental Haemorrhoids in Rats

Authors: Priyanka Sharma, Tarkewshwar Dubey, Hemalatha Siva

Abstract:

Hemorrhoids are one of the most common anorectal diseases around the world. Severalfactors are involved in causing hemorrhoids including irregularbowel function (constipation, diarrhea), exercise, gravity, low fiberdiet, pregnancy, obesity, high abdominal pressure, prolongedsitting, genetic factors, and aging. Pain, bleeding, itching,swelling and anal discharge are the symptoms of the disease. Due to limitedmodern pharmacotherapeutic options available for treatment, theherbal medicines remain the choice of therapy. Blumea lacera (Burm f.) DC. belonging to the Asteraceae family is a common plain land weed of Bangladesh. Traditionally it has been used for treatment of hemorrhoids.Considering the above fact, present study was aimed to validate the ethnomedicinal use of B. lacera leaves on experimental hemorrhoids in rats. The anti-hemorrhoid activity was performed by using croton oil induced rat models. The parameters studied were assessment of TNF-α and IL-6, Evans blue exudation, macroscopic severity score, recto-anal coefficient, histomorphological scores. Also, in vivo antioxidant parameters and histopathological studies were also performed. All paramaters exhibited significant anti-hemorrhoid activity. Moreover ethanolic extract of B. lacera (EBL) leaves 400mg/kg showed ameliorative effect oncroton oil induced hemorrhoids.In conclusion, EBL exhibitedbeneficial effect on croton oil- induced hemorrhoids and validates its ethnomedicinal use in treatment of piles.

Keywords: haemorrhoids, IL-6, piles, TNF-α

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2406 Gold Nanoparticle Conjugated with Andrographolide Ameliorates Viper Venom-Induced Inflammatory Response and Organ Toxicity in Animal Model

Authors: Sourav Ghosh, Antony Gomes

Abstract:

Since 1894 anti-snake venom serum (ASVS) is the only available treatment against snake envenomation, although there are many side effects and limitations. The need for a supportive treatment was felt for a long time to overcome the side effects and limitations of ASVS. Andrographolide conjugated with gold nanoparticle (A-GNP) has been found to antagonize viper venom-induced local damages. The present study was aimed to study the protective efficacy of A-GNP against Viper venom-induced inflammatory response and organ toxicity in animal model. Ethical clearance was obtained from animal experiments. Physico-chemical characterization of A-GNP was done by DLS (diameter and zeta potential), FE-SEM and XRD. Swiss albino male mice were divided into 4 groups: Gr.1-Sham control, Gr.2- Russell’s Viper venom (RVV) control, Gr.3- andrographolide treated and Gr.4- A-GNP treated. The 1/5th minimum lethal dose of RVV (500µg/kg, s.c.) was induced in animals of group 2, 3 & 4 animals, followed by treatment with andrographolide (100mg/kg, i.p.) and A-GNP (100mg/kg, i.v.) in group 3 & 4 animals, respectively. Blood was collected after 18 h, serum was prepared, and inflammatory markers (IL 1β, 6, 17a, 10, TNF α) and biochemical markers (AST, ACP, LDH, urea, creatinine) were assessed. Values were expressed as mean±SEM (n=4), one way ANOVA was done, P<0.05 was considered as statistically significant. DLS size showed the hydrodynamic diameter of A-GNP to be 230-260nm with polydispersity index of 0.103 and zeta potential was -18.32mV. XRD data confirmed the presence of crystalline gold in A-GNP, and FESEM indicated the presence of nearly spherical particle with size18-24nm.Treatment with A-GNP significantly decreased viper venom-induced proinflammatory markers (IL 1β, 6, 17, TNF α) increased anti-inflammatory markers (IL 10) and decreased organ toxicity markers (AST, ACP, LDH, urea, creatinine) in animal model. Venom neutralization efficacy of A-GNP was > andrographolide, which confirmed the increased efficacy of andrographolide after gold nanoparticle conjugation. Venom neutralization by A-GNP was due to anti-oxidant/anti-inflammatory activity of andrographolide, which showed increased efficacy after gold nanoparticle tagging. Thus, A-GNP may serve as a supportive therapy in snake-bite (against inflammatory response and organ toxicity) subject to further detail studies.

Keywords: andrographolide, gold nanoparticle, inflammatory response, organ toxicity, snake venom, snake venom neutralization, viper venom

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2405 Structural Changes Induced in Graphene Oxide Film by Low Energy Ion Beam Irradiation

Authors: Chetna Tyagi, Ambuj Tripathi, Devesh Avasthi

Abstract:

Graphene oxide consists of sp³ hybridization along with sp² hybridization due to the presence of different oxygen-containing functional groups on its edges and basal planes. However, its sp³ / sp² hybridization can be tuned by various methods to utilize it in different applications, like transistors, solar cells and biosensors. Ion beam irradiation can also be one of the methods to optimize sp² and sp³ hybridization ratio for its desirable properties. In this work, graphene oxide films were irradiated with 100 keV Argon ions at different fluences varying from 10¹³ to 10¹⁶ ions/cm². Synchrotron X-ray diffraction measurements showed an increase in crystallinity at the low fluence of 10¹³ ions/cm². Raman spectroscopy performed on irradiated samples determined the defects induced by the ion beam qualitatively. Also, identification of different groups and their removal with different fluences was done using Fourier infrared spectroscopy technique.

Keywords: graphene oxide, ion beam irradiation, spectroscopy, X-ray diffraction

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2404 Optimal Design of Linear Generator to Recharge the Smartphone Battery

Authors: Jin Ho Kim, Yujeong Shin, Seong-Jin Cho, Dong-Jin Kim, U-Syn Ha

Abstract:

Due to the development of the information industry and technologies, cellular phones have must not only function to communicate, but also have functions such as the Internet, e-banking, entertainment, etc. These phones are called smartphones. The performance of smartphones has improved, because of the various functions of smartphones, and the capacity of the battery has been increased gradually. Recently, linear generators have been embedded in smartphones in order to recharge the smartphone's battery. In this study, optimization is performed and an array change of permanent magnets is examined in order to increase efficiency. We propose an optimal design using design of experiments (DOE) to maximize the generated induced voltage. The thickness of the poleshoe and permanent magnet (PM), the height of the poleshoe and PM, and the thickness of the coil are determined to be design variables. We made 25 sampling points using an orthogonal array according to four design variables. We performed electromagnetic finite element analysis to predict the generated induced voltage using the commercial electromagnetic analysis software ANSYS Maxwell. Then, we made an approximate model using the Kriging algorithm, and derived optimal values of the design variables using an evolutionary algorithm. The commercial optimization software PIAnO (Process Integration, Automation, and Optimization) was used with these algorithms. The result of the optimization shows that the generated induced voltage is improved.

Keywords: smartphone, linear generator, design of experiment, approximate model, optimal design

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2403 Identification of Vulnerable Zone Due to Cyclone-Induced Storm Surge in the Exposed Coast of Bangladesh

Authors: Mohiuddin Sakib, Fatin Nihal, Rabeya Akter, Anisul Haque, Munsur Rahman, Wasif-E-Elahi

Abstract:

Surge generating cyclones are one of the deadliest natural disasters that threaten the life of coastal environment and communities worldwide. Due to the geographic location, ‘low lying alluvial plain, geomorphologic characteristics and 710 kilometers exposed coastline, Bangladesh is considered as one of the greatest vulnerable country for storm surge flooding. Bay of Bengal is possessing the highest potential of creating storm surge inundation to the coastal areas. Bangladesh is the most exposed country to tropical cyclone with an average of four cyclone striking every years. Frequent cyclone landfall made the country one of the worst sufferer within the world for cyclone induced storm surge flooding and casualties. During the years from 1797 to 2009 Bangladesh has been hit by 63 severe cyclones with strengths of different magnitudes. Though detailed studies were done focusing on the specific cyclone like Sidr or Aila, no study was conducted where vulnerable areas of exposed coast were identified based on the strength of cyclones. This study classifies the vulnerable areas of the exposed coast based on storm surge inundation depth and area due to cyclones of varying strengths. Classification of the exposed coast based on hazard induced cyclonic vulnerability will help the decision makers to take appropriate policies for reducing damage and loss.

Keywords: cyclone, landfall, storm surge, exposed coastline, vulnerability

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2402 Overhead Lines Induced Transient Overvoltage Analysis Using Finite Difference Time Domain Method

Authors: Abdi Ammar, Ouazir Youcef, Laissaoui Abdelmalek

Abstract:

In this work, an approach based on transmission lines theory is presented. It is exploited for the calculation of overvoltage created by direct impacts of lightning waves on a guard cable of an overhead high-voltage line. First, we show the theoretical developments leading to the propagation equation, its discretization by finite difference time domain method (FDTD), and the resulting linear algebraic equations, followed by the calculation of the linear parameters of the line. The second step consists of solving the transmission lines system of equations by the FDTD method. This enabled us to determine the spatio-temporal evolution of the induced overvoltage.

Keywords: lightning surge, transient overvoltage, eddy current, FDTD, electromagnetic compatibility, ground wire

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2401 Torque Loss Prediction Test Method of Bolted Joints in Heavy Commercial Vehicles

Authors: Volkan Ayik

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Loosening as a result of torque loss in bolted joints is one of the most encountered problems resulting in loss of connection between parts. The main reason for this is the dynamic loads to which the joints are subjected while the vehicle is moving. In particular, vibration-induced loads can loosen the joints in any size and geometry. The aim of this study is to study an improved method due to road-induced vibration in heavy commercial vehicles for estimating the vibration performance of bolted joints of the components connected to the chassis, before conducting prototype level vehicle structural strength tests on a proving ground. The frequency and displacements caused by the road conditions-induced vibration loads have been determined for the parts connected to the chassis, and various experimental design scenarios have been formed by matching specific components and vibration behaviors. In the studies, the performance of the torque, washer, test displacement, and test frequency parameters were observed by maintaining the connection characteristics on the vehicle, and the sensitivity ratios for these variables were calculated. As a result of these experimental design findings, tests performed on a developed device based on Junker’s vibration device and proving ground conditions versus test correlation levels were found.

Keywords: bolted joints, junker’s test, loosening failure, torque loss

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2400 In vitro P-Glycoprotein Modulation: Combinatorial Approach Using Natural Products

Authors: Jagdish S. Patel, Piyush Chudasama

Abstract:

Context: Over-expression of P-glycoprotein (P-gp) plays critical role in absorption of many drug candidates which results into lower bioavailability of the drug. P-glycoprotein also over expresses in many pathological conditions like diabetes, affecting the drug therapy. Modulation of P-gp expression using inhibitors can help in designing novel formulation enhancing the bioavailability of the drug in question. Objectives: The main focus of the study was to develop advanced glycation end products (AGEs) induced P-gp over expression in Caco-2 cells. Curcumin, piperine and epigallocatechin gallate were used to evaluate their P-gp inhibitory action using combinatorial approach. Materials and methods: Methylglyoxal (MG) induced P-gp over expression was checked in Caco-2 cells using real time PCR. P-gp inhibitory effects of the phytochemicals were measured after induction with MG alone and in combination of any two compounds. Cytotoxicity of each of the phytochemical was evaluated using MTT assay. Results: Induction with MG (100mM) significantly induced the over expression of P-glycoprotein in Caco-2 cells after 24 hr. Curcumin, piperine and epigallocatechin gallate alone significantly reduced the level of P-gp within 6 hr of treatment period monitored by real time PCR. The combination of any two phytochemical also down regulated the expression of P-gp in cells. Combinations of Curcumin and epigallocatechin gallate have shown significant down regulation when compared with other two combinations. Conclusions: Combinatorial approach for down regulating the expression of P-gp, in pathological conditions like diabetes, has demonstrated promising approach for therapeutic purpose.

Keywords: p-glycoprotein, curcumin, piperine, epigallocatechin gallate, p-gp inhibition

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2399 Prospective Randomized Trial of Na/K Citrate for the Prevention of Contrast-Induced Nephropathy in High-Risk Patients

Authors: Leili Iranirad, Mohammad Saleh Sadeghi, Seyed Fakhreddin Hejazi, Negar Vakili Razlighi

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Objective: Contrast-induced nephropathy (CIN) or contrast-induced acute kidney injury (CI-AKI) is an unknown acute kidney injury (AKI) occurring after exposure to contrast media (CM). Contrast agents are most often used for diagnostic procedures or therapeutic angiographic interventions. Recently, Na/K citrate as a urine alkalinization has been evaluated for the prevention of CIN. We conducted this experiment to evaluate the efficiency of Na/K citrate on CIN in high-risk patients treated with cardiac catheterization. Methods: A prospective randomized clinical trial was conducted on 400 patients having moderate to high-risk factors for CIN treated with elective percutaneous coronary intervention (PCI) and were assigned randomly to the control group or the Na/K citrate group. The Na/K citrate group (n=200) received 5 g Na/K citrate solution, which was diluted in 200 mL water two h before and four hours after the first administration and intravenous hydration for two h prior to and six h after the procedure, while the control group (n=200) only received intravenous hydration. Serum creatinine (SCr) was calculated prior to the contrast exposure and after 48 h. CIN was described as a 25% increase in creatinine of serum (SCr) or >0.5 mg/dl 48 h after contrast administration. Results: CIN was observed in 33 patients (16.5%) in the control group and in 6 patients (3%) in the Na/K citrate group. A significant variation was recorded in the CIN incidence between the two groups 48 h after the radiocontrast agent administration (p < 0.001). Conclusion: Our results show that Na/K citrate is useful and substantially reduces the incidence of CIN.

Keywords: contrast media, citrate, PCI

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2398 A Systematic Review on the Whole-Body Cryotherapy versus Control Interventions for Recovery of Muscle Function and Perceptions of Muscle Soreness Following Exercise-Induced Muscle Damage in Runners

Authors: Michael Nolte, Iwona Kasior, Kala Flagg, Spiro Karavatas

Abstract:

Background: Cryotherapy has been used as a post-exercise recovery modality for decades. Whole-body cryotherapy (WBC) is an intervention which involves brief exposures to extremely cold air in order to induce therapeutic effects. It is currently being investigated for its effectiveness in treating certain exercise-induced impairments. Purpose: The purpose of this systematic review was to determine whether WBC as a recovery intervention is more, less, or equally as effective as other interventions at reducing perceived levels of muscle soreness and promoting recovery of muscle function after exercise-induced muscle damage (EIMD) from running. Methods: A systematic review of the current literature was performed utilizing the following MeSH terms: cryotherapy, whole-body cryotherapy, exercise-induced muscle damage, muscle soreness, muscle recovery, and running. The databases utilized were PubMed, CINAHL, EBSCO Host, and Google Scholar. Articles were included if they were published within the last ten years, had a CEBM level of evidence of IIb or higher, had a PEDro scale score of 5 or higher, studied runners as primary subjects, and utilized both perceived levels of muscle soreness and recovery of muscle function as dependent variables. Articles were excluded if subjects did not include runners, if the interventions included PBC instead of WBC, and if both muscle performance and perceived muscle soreness were not assessed within the study. Results: Two of the four articles revealed that WBC was significantly more effective than treatment interventions such as far-infrared radiation and passive recovery at reducing perceived levels of muscle soreness and restoring muscle power and endurance following simulated trail runs and high-intensity interval running, respectively. One of the four articles revealed no significant difference between WBC and passive recovery in terms of reducing perceived muscle soreness and restoring muscle power following sprint intervals. One of the four articles revealed that WBC had a harmful effect compared to CWI and passive recovery on both perceived muscle soreness and recovery of muscle strength and power following a marathon. Discussion/Conclusion: Though there was no consensus in terms of WBC’s effectiveness at treating exercise-induced muscle damage following running compared to other interventions, it seems as though WBC may at least have a time-dependent positive effect on muscle soreness and recovery following high-intensity interval runs and endurance running, marathons excluded. More research needs to be conducted in order to determine the most effective way to implement WBC as a recovery method for exercise-induced muscle damage, including the optimal temperature, timing, duration, and frequency of treatment.

Keywords: cryotherapy, physical therapy intervention, physical therapy, whole body cryotherapy

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2397 Antioxidant Potential of Pomegranate Rind Extract Attenuates Pain, Inflammation and Bone Damage in Experimental Rats

Authors: Ritu Karwasra, Surender Singh

Abstract:

Inflammation is an important physiological response of the body’s self-defense system that helps in eliminating and protecting organism from harmful stimuli and in tissue repair. It is a highly regulated protective response which helps in eliminating the initial cause of cell injury, and initiates the process of repair. The present study was designed to evaluate the ameliorative effect of pomegranate rind extract on pain and inflammation. Hydroalcoholic standardized rind extract of pomegranate at doses 50, 100 and 200 mg/kg and indomethacin (3 mg/kg) was tested against eddy’s hot plate induced thermal algesia, carrageenan (acute inflammation) and Complete Freund’s Adjuvant (chronic inflammation) induced models in Wistar rats. Parameters analyzed were inhibition of paw edema, measurement of joint diameter, levels of GSH, TBARS, SOD, TNF-α, radiographic imaging, tissue histology and synovial expression of pro-inflammatory cytokine receptor (TNF-R1). Radiological and light microscopical analysis were carried out to find out the bone damage in CFA-induced chronic inflammatory model. Findings of the present study revealed that pomegranate rind extract at a dose of 200 mg/kg caused a significant (p<0.05) reduction in paw swelling in both the inflammatory models. Nociceptive threshold was also significantly (p<0.05) improved. Immunohistochemical analysis of TNF-R1 in CFA-induced group showed elevated level, whereas reduction in level of TNF-R1 was observed in pomegranate (200 mg/kg). Henceforth, we might say that pomegranate produced a dose-dependent reduction in inflammation and pain along with the reduction in levels of oxidative stress markers and tissue histology, and the effect was found to be comparable to that of indomethacin. Thus, it can be concluded that pomegranate is a potential therapeutic target in the pathogenesis of inflammation and pain, and punicalagin is the major constituents found in rind extract might be responsible for the activity.

Keywords: carrageenan, inflammation, nociceptive-threshold, pomegranate, histopathology

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2396 In vivo Antidiabetic and in vitro Antioxidant Activity of Myrica salicifolia Hochst. ex A. Rich. (Myricaceae) Root Extract in Streptozotocin-Induced Diabetic Mice

Authors: Yohannes Kelifa, Gomathi Periasamy, Aman Karim

Abstract:

Introduction: Diabetes mellitus has become a major public health and economical problem across the globe. Modern antidiabetic drugs have a number of limitations, and scientific investigation of traditional herbal remedies used for diabetes may provide novel leads for the development of new antidiabetic drugs that can be used as alternative or complementary to available antidiabetic allopathic medications. Though Myrica salicifolia Hochst. ex A. Rich. is used for the management of diabetes in Ethiopian traditional medicine, there was no previous scientific evidence about its antidiabetic effect to the authors’ knowledge. This study was undertaken to evaluate the antidiabetic activity the root extracts of Myrica salicifolia in streptozotocin (STZ)-induced diabetic mice. Methods: Experimental diabetes was induced by intraperitoneal administration of STZ (150 mg/kg) in male mice. Diabetic mice were treated with oral doses of M. salicifolia root extracts at 200, 400 and 600 mg/kg, and its fractions (chloroform, ethyl acetate, n-butanol and aqueous) at a dose of 400 mg/kg daily for 15 days. Fasting blood glucose level (BGL) was measured at 0, 5th,10th, and 15th day. The free radical scavenging activity of the crude extract was determined using in vitro by DPPH assay. The statistical significance was assessed by one-way ANOVA, followed by Tukey’s multiple comparison tests. Results were considered significant when p < 0.05. Results: Daily administration of the M. salicifolia 80% methanol root extracts (at three different doses (200, 400 and 600 mg/kg) significantly (p < 0.05, p < 0.01 and p < 0.001) reduced fasting BGL compared with diabetic control. The aqueous and butanol fractions at a dose of 400 mg/kg resulted in maximum reduction of fasting BGL by 42.39%, and 52.13%, respectively at the 15th day in STZ-induced diabetic mice. Free radical scavenging activity of the 80% methanol extract of M. salicifolia was comparable to ascorbic acid. The IC50 values of the crude extract and ascorbic acid (a reference compound) were found to be 4.54 μg/ml and 4.39 μg/ml, respectively. Conclusion: These findings demonstrated that the methanolic extracts of M. salicifolia root and its fractions (n-butanol and aqueous) exhibit a significant antihyperglycemic activity in STZ-induced diabetic mice. Furthermore, the result of the present study indicates that M. salicifolia root extract is a potential source of natural antioxidants.

Keywords: antidiabetic, diabetes mellitus, DPPH, mice, Myrica salicifolia, streptozotocin

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2395 Magneto-Solutal Convection in Newtonian Fluid Layer with Modulated Gravity

Authors: Om Prakash Keshri, Anand Kumar, Vinod K. Gupta

Abstract:

In the present study, the effect of gravity modulation on the onset of convection in viscous fluid layer under the influence of induced magnetic field, salted from above on the boundaries, has been investigated. Linear and nonlinear stability analysis has been performed. A linear stability analysis is performed to show that the gravity modulation can significantly affect the stability limits of the system. A method based on small amplitude of the modulation is used to compute the critical value of Rayleigh number and wave number. The effect of Smith number, salute Rayleigh number and magnetic Prandtl number on the stability of the system is investigated.

Keywords: viscous fluid, induced magnetic field, gravity modulation, salute convection

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2394 Antineoplastic Effect of Tridham and Penta Galloyl Glucose in Experimental Mammary Carcinoma Bearing Rats

Authors: Karthick Dharmalingam, Stalin Ramakrishnan, Haseena Banu Hedayathullah Khan, Sachidanandanam Thiruvaiyaru Panchanadham, Shanthi Palanivelu

Abstract:

Background: Breast cancer is arising as the most dreadful cancer affecting women worldwide. Hence, there arises a need to search and test for new drugs. Herbal formulations used in Siddha preparations are proved to be effective against various types of cancer. They also offer advantage through synergistic amplification and diminish any possible adverse effects. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio and has been used for the treatment of mammary carcinoma. Objective: To study the restorative effect of Tridham and penta galloyl glucose (a component of TD) on DMBA induced mammary carcinoma in female Sprague Dawley rats. Materials and Methods: Rats were divided into seven groups of six animals each. Group I (Control) received corn oil. Group II– mammary carcinoma was induced by DMBA dissolved in corn oil single dose orally. Group III and Group IV were induced with DMBA and subsequently treated with Tridham and penta galloyl glucose, respectively for 48 days. Group V was treated with DMBA and subsequently with a standard drug, cyclophosphamide. Group VI and Group VII were given Tridham and penta galloyl glucose alone, respectively for 48 days. After the experimental period, the animals were sacrificed by cervical decapitation. The mammary gland tissue was excised and levels of antioxidants were determined by biochemical assay. p53 and PCNA expression were accessed using immunohistochemistry. Nrf-2, Cox-2 and caspase-3 protein expression were studied by Western Blotting analysis. p21, Bcl-2, Bax, Bad and caspase-8 gene expression were studied by RT-PCR. Results: Histopathological studies confirmed induction of mammary carcinoma in DMBA induced rats and treatment with TD and PGG resulted in regression of tumour. The levels of enzymic and non-enzymic antioxidants were decreased in DMBA induced rats when compared to control rats. The levels of cell cycle inhibitory markers and apoptotic markers were decreased in DMBA induced rats when compared to control rats. These parameters were restored to near normal levels on treatment with Tridham and PGG. Conclusion: The results of the present study indicate the antineoplastic effect of Tridham and PGG are exerted through the modulation of antioxidant status and expression of cell cycle regulatory markers as well as apoptotic markers. Acknowledgment: Financial assistance provided in the form of ICMR-SRF by Indian Council of Medical Research (ICMR), India is gratefully acknowledged here.

Keywords: antioxidants, Mammary carcinoma, pentaGalloyl glucose, Tridham

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2393 Biochemical and Cellular Correlates of Essential Oil of Pistacia Integerrima against in vitro and Murine Models of Bronchial Asthma

Authors: R. L. Shirole, N. L. Shirole, R. B. Patil, M. N. Saraf

Abstract:

The present investigation aimed to elucidate the probable mechanism of antiasthmatic action of essential oil of Pistacia integerrima J.L. Stewart ex Brandis galls (EOPI). EOPI was investigated for its potential antiasthmatic action using in vitro antiallergic assays mast cell degranulation and soyabean lipoxidase enzyme activit, and spasmolytic action using isolated guinea pig ileum preparation. In vivo studies included lipopolysaccharide-induced bronchial inflammation in rats and airway hyperresponsiveness in ovalbumin in sensitized guinea pigs using spirometry. Data was analysed by GraphPad Prism 5.01 and results were expressed as means ± SEM. P < 0.05 was considered to be significant. EOPI inhibits 5-lipoxidase enzyme activity, DPPH scavenging activity and erythropoietin- induced angiogenesis. It showed dose dependent anti-allergic activity by inhibiting compound 48/80 induced mast cell degranulation. The finding that essential oil induced inhibition of transient contraction of acetylcholine in calcium free medium, and relaxation of S-(-)-Bay 8644-precontracted isolated guinea pig ileum jointly suggest that suggesting that the L-subtype Cav channel is involved in spasmolytic action of EOPI. Treatment with EOPI dose dependently (7.5, 15 and 30 mg/kg i.p.) inhibited lipopolysaccharide- induced increased in total cell count, neutrophil count, nitrate-nitrite, total protein, albumin levels in bronchoalveolar fluid and myeloperoxidase levels in lung homogenates. Mild diffused lesions involving focal interalveolar septal, intraluminal infiltration of neutrophils were observed in EOPI (7.5 &15 mg/kg) pretreated while no abnormality was detected in EOPI (30 mg/kg) and roflumilast (1mg/kg) pretreated rats. Roflumilast was used as standard. EOPI reduced the respiratory flow due to gasping in ovalbumin sensitized guinea pigs. The study demonstrates the effectiveness of EOPI in bronchial asthma possibly related to its ability to inhibit L-subtype Cav channel, mast cell stabilization, antioxidant, angiostatic and through inhibition of 5-lipoxygenase enzyme.

Keywords: asthma, lipopolysaccharide, spirometry, Pistacia integerrima J.L. Stewart ex Brandis, essential oil

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2392 Colour Formation and Maillard Reactions in Spray-Dried Milk Powders

Authors: Zelin Zhou, Timothy Langrish

Abstract:

Spray drying is the final stage of milk powder production. Traditionally, the quality of spray-dried milk powders has mainly been assessed using their physical properties, such as their moisture contents, while chemical changes occurring during the spray drying process have often been ignored. With growing concerns about food quality, it is necessary to establish a better understanding of heat-induced degradation due to the spray-drying process of skim milk. In this study, the extent of thermal degradation for skim milk in a pilot-scale spray dryer has been investigated using different inlet gas temperatures. The extent of heat-induced damage has been measured by the formation of advanced Maillard reaction products and the loss of soluble proteins at pH 4.6 as assessed by a fluorometric method. A significant increase in the extent of thermal degradation has been found when the inlet gas temperature increased from 170°C to 190°C, suggesting protein unfolding may play an important role in the kinetics of heat-induced degradation for milk in spray dryers. Colour changes of the spray-dried skim milk powders have also been analysed using a standard lighting box. Colourimetric analysis results were expressed in CIELAB colour space with the use of the E index (E) and the Chroma (C) for measuring the difference between colours and the intensity of the colours. A strong linear correlation between the colour intensity of the spray-dried skim milk powders and the formation of advanced Maillard reaction products has been observed.

Keywords: colour formation, Maillard reactions, spray drying, skim milk powder

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2391 Effect of Post and Pre Induced Treatment with Hesperidin in N-Methyl N-Nitrosourea Induced Mammary Gland Cancer in Female Sprague-Dawley Rats

Authors: Vinay Kumar Theendra

Abstract:

The main objective of the study is to evaluate the effectiveness of hesperidin in the treatment of breast cancer and causing less (or) no bone marrow depression which is the major side effect of the present anticancer drugs treating breast cancer, also to evaluate the mechanisms through which these compounds are exerting their effect. Breast cancer is induced by administering N-methyl N-Nitrosourea (MNU) at a dose of 50mg/kg body weight. Upon the termination of the experiment, the animals were sacrificed by the method of cervical dislocation. The animals were dissected along the ventral midline and were grossly examined for the presence of tumors. Then the tumours were removed along with the stroma. Vascular endothelial growth factor (VEGF) levels were estimated by using ELISA method. The first occurrence of palpable tumors was eight weeks after carcinogen treatment and the final tumour incidence was 100% in the MNU alone and topical treated rats. Whereas in rats of other treatment groups there is decreased tumour incidence which might be due to their antitumour activity. Hesperidin therapy inhibited angiogenesis which can be evident from the significant reduction in serum as well as tumour VEGF concentrations in comparison to the untreated mammary carcinoma bearing rats. Hesperidin is promising agents that exert direct antitumor and also antiangiogenic, antiproliferative and anti-inflammatory activities. Even though the potency is little lesser than standard drug vincristine, it has been proved to be safe without effecting haematological count.

Keywords: hesperidin, VEGF, COX 2, N-methyl N-nitrosourea

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2390 Magnesium Ameliorates Lipopolysaccharide-Induced Liver Injury in Mice

Authors: D. M. El-Tanbouly, R. M. Abdelsalam, A. S. Attia, M. T. Abdel-Aziz

Abstract:

Lipopolysaccharide (LPS) endotoxin, a component of the outer membrane of Gram-negative bacteria, is involved in the pathogenesis of sepsis. LPS administration induces systemic inflammation that mimics many of the initial clinical features of sepsis and has deleterious effects on several organs including the liver and eventually leading to septic shock and death. The present study aimed to investigate the protective effect of magnesium, a well-known cofactor in many enzymatic reactions and a critical component of the antioxidant system, on hepatic damage associated with LPS induced- endotoxima in mice. Mg (20 and 40 mg/kg, po) was administered for 7 consecutive days. Systemic inflammation was induced one hour after the last dose of Mg by a single dose of LPS (2 mg/kg, ip) and three hours thereafter plasma was separated, animals were sacrificed and their livers were isolated. LPS-treated mice suffered from hepatic dysfunction revealed by histological observation, elevation in plasma transaminases activities, C-reactive protein content and caspase-3, a critical marker of apoptosis. Liver inflammation was evident by elevation in liver cytokines contents (TNF-α and IL-10) and myeloperoxidase (MPO) activity. Additionally, oxidative stress was manifested by increased liver lipoperoxidation, glutathione depletion, elevated total nitrate/nitrite (NOx) content and glutathione peroxidase (GPx) activity. Pretreatment with Mg largely mitigated these alternations through its anti-inflammatory and antioxidant potentials. Mg, therefore, could be regarded as an effective strategy for prevention of liver damage associated with septicemia.

Keywords: LPS, liver damage, magnesium, septicemia

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2389 Saponins from the Fruits of Solanum anguivi Reverse Hyperglycemia, Hyperlipidemia and Increase Antioxidant Status in Stretozotocin Induced Diabetic Rats

Authors: Isaac Gbadura Adanlawo, Olusola Olalekan Elekofehinti

Abstract:

This work investigated the antihyperglycemic, antioxidant and antihyperlipidemic effects of saponins from the fruit of Solanum anguivi, a plant generally used in folk medicine to treat diabetes and hypertension and to compare its effect with metformin in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in albino rats by administration of STZ (65 mg/kg) intraperitoneally. Saponin (40 and 100 mg/kg) was administered by oral gavage once daily for 21 days. Metformin (200 mg/kg b.w.) was administered as the positive control. The effect of saponin on blood glucose, serum lipids and enzymatic antioxidants defense systems, like superoxide dismutase (SOD), catalase (CAT), as well as MDA levels in serum, liver and pancreas were studied. Saponins from S. anguivi fruits reduced the blood glucose, total cholesterol (TC), triglycerides (TG) and low-density lipoprotein (LDL) levels in STZ-diabetic rats. They also significantly abolished the increase in MDA level in serum, liver and pancreas of diabetic rats. The activities of SOD and CAT in serum, liver and pancreas were significantly increased as well as concentration of HDL in the serum. Metformin had the same effect as saponin but saponins seems to be more potent in reducing serum TC, TG, LDL, and MDA, and increasing SOD and CAT. Conclusions: These results suggest that saponins from S. anguivi fruits have anti-diabetic and antihypercholesterolemic, antihypertriglyceridemic antiperoxidative activities mediated through their antioxidant properties. Also, saponins appeared to have more hypolipidemic, antiperoxidative and antioxidant activity than metformin.

Keywords: saponin, diabetes, metformin, streptozotocin, Solanum anguivi

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2388 Qualitative and Quantitative Analysis of Uranium in Ceramic Tiles Using Laser-Induced Breakdown Spectroscopy and Gamma-Ray Spectroscopy

Authors: Reem M. Altuwirqi, Mohja S. Summan, Entesar A. Ganash, Safia H. Hamidalddin, Tamer E. Youssef, Mohammed A. Gondal

Abstract:

Laser-Induced Breakdown Spectroscopy (LIBS) technique using 1064 nm Nd: YAG laser was optimized and applied for investigating the existence of radioactive elements (uranium) in twenty-six different ceramic tiles. These tiles were collected from the local Saudi market. Qualitative and quantitative analysis for trace radioactive elements like uranium in these samples was achieved using LIBS. The plasma parameters such as temperature and electron density were calculated to confirm that the plasma generated by the tile samples under laser irradiation can be related to analyte concentrations. In order to perform a quantitative analysis, calibration curves were constructed for two uranium lines (U II (424.166 nm) and U II (424.437 nm)). The Uranium activity concentration in Bq/kg for each sample was measured. Cross-validation of LIBS results with a conventional technique such as Gamma-Ray spectroscopy was also carried out for five ceramic samples. The results show that the LIBS method is an effective way of determining radioactive elements such as uranium in ceramic tiles. Moreover, the uranium concentrations of the investigated samples were below the permissible safe limit for building materials in the majority of samples. Such LIBS system could be applied to determine the presence of natural radioactive elements in ceramic tiles and their radioactivity level rapidly to ensure that they are under the safe allowed limit.

Keywords: laser-induced breakdown spectroscopy, gamma-ray spectroscopy, natural radioactivity, uranium, ceramic tiles

Procedia PDF Downloads 143
2387 Camptothecin Promotes ROS-Mediated G2/M Phase Cell Cycle Arrest, Resulting from Autophagy-Mediated Cytoprotection

Authors: Rajapaksha Gedara Prasad Tharanga Jayasooriya, Matharage Gayani Dilshara, Yung Hyun Choi, Gi-Young Kim

Abstract:

Camptothecin (CPT) is a quinolone alkaloid which inhibits DNA topoisomerase I that induces cytotoxicity in a variety of cancer cell lines. We previously showed that CPT effectively inhibited invasion of prostate cancer cells and also combined treatment with subtoxic doses of CPT and TNF-related apoptosis-inducing ligand (TRAIL) potentially enhanced apoptosis in a caspase-dependent manner in hepatoma cancer cells. Here, we found that treatment with CPT caused an irreversible cell cycle arrest in the G2/M phase. CPT-induced cell cycle arrest was associated with a decrease in protein levels of cell division cycle 25C (Cdc25C) and increased the level of cyclin B and p21. The CPT-induced decrease in Cdc25C was blocked in the presence of proteasome inhibitor MG132, thus reversed the cell cycle arrest. In addition to that treatment of CPT-increased phosphorylation of Cdc25C was the resulted of activation of checkpoint kinase 2 (Chk2), which was associated with phosphorylation of ataxia telangiectasia-mutated. Interestingly CPT induced G2/M phase of the cell cycle arrest is reactive oxygen species (ROS) dependent where ROS inhibitors NAC and GSH reversed the CPT-induced cell cycle arrest. These results further confirm by using transient knockdown of nuclear factor-erythroid 2-related factor 2 (Nrf2) since it regulates the production of ROS. Our data reveal that treatment of siNrf2 increased the ROS level as well as further increased the CPT induce G2/M phase cell cycle arrest. Our data also indicate CPT-enhanced cell cycle arrest through the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more decreased the Cdc25C expression and protein expression of p21 and cyclin B. These findings indicate that Chk2-mediated phosphorylation of Cdc25C plays a major role in G2/M arrest by CPT.

Keywords: camptothecin, cell cycle, checkpoint kinase 2, nuclear factor-erythroid 2-related factor 2, reactive oxygen species

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