Search results for: anti-tubercular therapy induced hepatotoxicity
3690 Numerical Study on the Cavity-Induced Piping Failure of Embankment
Authors: H. J. Kim, G. C. Park, K. C. Kim, J. H. Shin
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Cavities are frequently found beneath conduits on pile foundations in old embankments. Cavity reduces seepage length significantly and consequently causes piping failure of embankments. Case studies of embankment failures indicate that the relative settlement between ground and pile supported-concrete conduit was the main reason of the cavity. In this paper, an attempt to simulate the cavity-induced piping failure mechanism was made using finite element numerical method. Piping potential is examined by carrying out parametric study for influencing factors such as cavity length, water level, and flow conditions. The concentration of hydraulic gradient adjacent to cavity was found. It is found that the hydraulic gradient close to the cavity exceeds considerably the critical hydraulic gradient causing piping. Piping failure potential due to the existence of cavity is evaluated and contour map for the potential risk of an embankment for piping failure is proposed.Keywords: cavity, hydraulic gradient, levee, piping
Procedia PDF Downloads 5203689 The Effectiveness of Kinesiotaping Methods in Rehabilitation Therapy
Authors: Ana-Katarina Nikich
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Background: The kinesiotaping method is often used in physiotherapy and rehabilitation. The purpose of this study was to evaluate the effectiveness of taping in the rehabilitation process of patients. Materials and methods: The study involved 90 male and female patients (the average age was 40-50 years) with various conditions requiring rehabilitation, such as injuries of the musculoskeletal system, sports injuries and other ailments. All patients were divided into two groups: experimental (n=40) and control (n=50). Both groups received 20 days of standard rehabilitation. In the experimental group, kinesiotaping methods were used, taking into account the individual characteristics of each patient. The control group performed regular exercises and physical therapy, but without using kinesiotape. During the study, physical parameters were monitored, interviews were conducted and the conditions of patients from both groups were compared. Results and discussion: The use of the kinesiotaping method in the rehabilitation process led to a significant improvement in physical parameters and pain reduction in patients. Significant improvement (p <0.005) was observed in all evaluated parameters among the patients of the experimental group. The control group also showed sufficient improvement (p <0.005), but the percentage of the experimental group was higher. As a result of the observation, the patients of the experimental group showed faster and more complete rehabilitation compared to the control group. The use of the kinesiotaping method allows to reduce the load on the damaged areas, improve blood circulation and lymphatic drainage, as well as increase stability and coordination of movements. Conclusions: Kinesiotaping as one of the modern therapeutic methods has shown its effectiveness in the rehabilitation process, contributing to the optimal recovery of patients with various conditions requiring rehabilitation. The use of tapes should be included in a comprehensive rehabilitation program to achieve the best results and reduce recovery time.Keywords: kinesiotaping, rehabilitation, therapy, pain
Procedia PDF Downloads 703688 Alpha-To-Omega Phase Transition in Bulk Nanostructured Ti and (α+β) Ti Alloys
Authors: Askar Kilmametov, Julia Ivanisenko, Boris Straumal, Horst Hahn
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The high-pressure α- to ω-phase transition was discovered in elemental Ti and Zr fifty years ago using static high pressure and then observed to appear between 2 and 12 GPa at room temperature, depending on the experimental technique, the pressure environment, and the sample purity. The fact that ω-phase is retained in a metastable state in ambient condition after the removal of the pressure has been used to check the changes in magnetic and superconductive behavior, electron band structure and mechanical properties. However, the fundamental knowledge on a combination of both mechanical treatment and high applied pressure treatments for ω-phase formation in Ti alloys is currently lacking and has to be studied in relation to improved mechanical properties of bulk nanostructured states. In the present study, nanostructured (α+β) Ti alloys containing β-stabilizing elements such as Co, Fe, Cr, Nb were performed by severe plastic deformation, namely high pressure torsion (HPT) technique. HPT-induced α- to ω-phase transformation was revealed in dependence on applied pressure and shear strains by means of X-ray diffraction, transmission electron microscopy, and differential scanning calorimetry. The transformation kinetics was compared with the kinetics of pressure-induced transition. Orientation relationship between α-, β- and ω-phases was taken into consideration and analyzed according to theoretical calculation proposed earlier. The influence of initial state before HPT appeared to be considerable for subsequent α- to ω-phase transition. Thermal stability of the HPT-induced ω-phase was discussed as well in the frame of mechanical behavior of Ti and Ti-based alloys produced by shear deformation under high applied pressure.Keywords: bulk nanostructured materials, high pressure phase transitions, severe plastic deformation, titanium alloys
Procedia PDF Downloads 4193687 Quantitative Elemental Analysis of Cyperus rotundus Medicinal Plant by Particle Induced X-Ray Emission and ICP-MS Techniques
Authors: J. Chandrasekhar Rao, B. G. Naidu, G. J. Naga Raju, P. Sarita
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Particle Induced X-ray Emission (PIXE) and Inductively Coupled Plasma Mass Spectroscopy (ICP-MS) techniques have been employed in this work to determine the elements present in the root of Cyperus rotundus medicinal plant used in the treatment of rheumatoid arthritis. The elements V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Rb, and Sr were commonly identified and quantified by both PIXE and ICP-MS whereas the elements Li, Be, Al, As, Se, Ag, Cd, Ba, Tl, Pb and U were determined by ICP-MS and Cl, K, Ca, Ti and Br were determined by PIXE. The regional variation of elemental content has also been studied by analyzing the same plant collected from different geographical locations. Information on the elemental content of the medicinal plant would be helpful in correlating its ability in the treatment of rheumatoid arthritis and also in deciding the dosage of this herbal medicine from the metal toxicity point of view. Principal component analysis and cluster analysis were also applied to the data matrix to understand the correlation among the elements.Keywords: PIXE, CP-MS, elements, Cyperus rotundus, rheumatoid arthritis
Procedia PDF Downloads 3333686 Hepatoprotective Effect of Ethyl Acetate Fraction of Ficus carica L. Leaves against Carbon Tetrachloride-Induced Toxicity in vitro and in vivo
Authors: Syeda Hira, Muhammad Gulfraz
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Background: Liver diseases cause serious health issues. Plants contain active compounds that significantly help in the treatment of various diseases. Ficus carica is traditionally used for the treatment of liver diseases. The purpose of the present study was the isolation and identification of active components from F.carica leaves which are responsible for hepatoprotective activity. Methods: The study was designed to identify the most active hepatoprotective sub-fraction from ethyl acetate fraction of Ficus carica by in vitro study and evaluation of its in vivo hepatoprotective effect in animal models. Ethyl acetate fraction was subjected to column, and a total of eight sub-fractions were obtained. In vitro, the hepatoprotective effect of all sub-fractions was determined on HepG2 cell lines. Toxicity was induced by CCl₄ (Carbon tetrachloride), and silymarin was used as a positive control. On the basis of the results, the most active sub-fraction was subjected to LC-MS and FT-IR analysis for the identification of bioactive compounds. In vivo, the hepatoprotective effect was determined in mice. Toxicity was induced by CCl₄; at the end of the experiment, biochemical parameters such as ALT, AST, ALP, bilirubin, and total protein were estimated in serum. Histopathology of liver tissues was also done. Results: Sub-fraction FVI exhibited significant (P<0.05) hepatoprotective activity as compared to other sub-fractions, which was almost similar to the standard drug silymarin. Six known bioactive compounds were identified from this sub-fraction after LC-MS analysis. In vivo, the hepatoprotective activity of sub-fraction FVI was evaluated in CCl₄-induced toxicated mice. Administration of CCl₄ significantly increased level of ALT (Alanine transaminase), AST (Aspartate aminotransferase), ALP (Alkaline phosphatase), and bilirubin and decreased the total protein. Treatment with sub-fraction FVI significantly (p<0.05) reversed the level of these biomarkers toward normal at both doses of 25 mg/kg and 50 mg/kg. Conclusion: Our findings confirmed the hepatoprotective effect of ethyl acetate fraction of F.carica. It could be a good candidate for the development of a natural hepatoprotective drug; pre-clinical investigation on ethyl acetate fraction is recommended.Keywords: Ficus carica, hepatoprotective, CCl₄, bioactive compounds, liver markers
Procedia PDF Downloads 623685 Role of Zinc in Catch-Up Growth of Low-Birth Weight Neonates
Authors: M. A. Abdel-Wahed, Nayera Elmorsi Hassan, Safaa Shafik Imam, Ola G. El-Farghali, Khadija M. Alian
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Low-birth-weight is a challenging public health problem. Aim: to clarify role of zinc on enhancing catch-up growth of low-birth-weight and find out a proposed relationship between zinc effect on growth and the main growth hormone mediator, IGF-1. Methods: Study is a double-blind-randomized-placebo-controlled trial conducted on low-birth-weight-neonates delivered at Ain Shams University Maternity Hospital. It comprised 200 Low-birth-weight-neonates selected from those admitted to NICU. Neonates were randomly allocated into one of the following two groups: group I: low-birth-weight; AGA or SGA on oral zinc therapy at dose of 10 mg/day; group II: Low-birth-weight; AGA or SGA on placebo. Anthropometric measurements were taken including birth weight, length; head, waist, chest, mid-upper arm circumferences, triceps and sub-scapular skin-fold thicknesses. Results: At 12-month-old follow-up visit, mean weight, length; head (HC), waist, chest, mid-upper arm circumferences and triceps; also, infant’s proportions had values ≥ 10th percentile for weight, length and HC were significantly higher among infants of group I when compared to those of group II. Oral zinc therapy was associated with 24.88%, 25.98% and 19.6% higher proportion of values ≥ 10th percentile regarding weight, length and HC at 12-month-old visit, respectively [NNT = 4, 4 and 5, respectively]. Median IGF-1 levels measured at 6 months were significantly higher in group I compared to group II (median (range): 90 (19 – 130) ng/ml vs. 74 (21 – 130) ng/ml, respectively, p=0.023). Conclusion: Oral zinc therapy in low-birth-weight neonates was associated with significantly more catch-up growth at 12-months-old and significantly higher serum IGF-1 at 6-month-old.Keywords: low-birth-weight, zinc, catch-up growth, neonates
Procedia PDF Downloads 4163684 A Construct to Perform in Situ Deformation Measurement of Material Extrusion-Fabricated Structures
Authors: Daniel Nelson, Valeria La Saponara
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Material extrusion is an additive manufacturing modality that continues to show great promise in the ability to create low-cost, highly intricate, and exceedingly useful structural elements. As more capable and versatile filament materials are devised, and the resolution of manufacturing systems continues to increase, the need to understand and predict manufacturing-induced warping will gain ever greater importance. The following study presents an in situ remote sensing and data analysis construct that allows for the in situ mapping and quantification of surface displacements induced by residual stresses on a specified test structure. This proof-of-concept experimental process shows that it is possible to provide designers and manufacturers with insight into the manufacturing parameters that lead to the manifestation of these deformations and a greater understanding of the behavior of these warping events over the course of the manufacturing process.Keywords: additive manufacturing, deformation, digital image correlation, fused filament fabrication, residual stress, warping
Procedia PDF Downloads 883683 Magnetoelectric Effect in Polyvinylidene Fluoride Beta Phase Thin Films
Authors: Belouadah Rabah, Guyomar Daneil, Guiffard Benoit
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The magnetoelectric (ME) materials has dielectric polarization induced by the magnetic field or induced magnetization under an electric field. A strong ME effect requires the simultaneous presence of magnetic moments and electric dipoles. In the last decades, extensive research has been conducted on the ME effect in single phase and composite materials. This article reported the results obtained with two samples, the first is mono layer of PVDF bi-stretched and the second is the multi layer PVDF bi-stretched with the Polyurethane filled with micro particles magnetic Fe3O4 (PU+2% Fe3O4). Compare with non ME material like Alumine, a large ME polarization coefficient for the two samples was obtained. The piezoelectric properties of the PVDF and elastic proprieties of Pu+2% Fe3O4 give a big linear ME coefficient of the multi layer PVDF/(Pu+2% Fe3O4) than in the monolayer of PVDF.Keywords: magnetoelectric effect, polymers, magnetic particles, composites, films
Procedia PDF Downloads 3953682 Evaluation of the Diagnostic Potential of IL-2 after Specific Antigen Stimulation with PE35 (Rv3872) and PPE68 (Rv3873) for the Discrimination of Active and Latent Tuberculosis
Authors: Shima Mahmoudi, Babak Pourakbari, Setareh Mamishi, Mostafa Teymuri, Majid Marjani
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Although cytokine analysis has greatly contributed to the understanding of tuberculosis (TB) pathogenesis, data on cytokine profiles that might distinguish progression from latency of TB infection are scarce. Since PE/PPE proteins are known to induce strong humoral and cellular immune responses, the aim of this study was to evaluate the diagnostic potential of interleukin-2 (IL-2) as biomarker after specific antigen stimulation with PE35 and PPE68 for the discrimination of active and latent tuberculosis infection (LTBI). The production of IL-2 was measured in the antigen-stimulated whole-blood supernatants following stimulation with recombinant PE35 and PPE68. All the patients with active TB and LTBI had positive QuantiFERON-TB Gold in Tube test. The level of IL-2 following stimulation with recombinant PE35 and PPE68 were significantly higher in LTBI group than in patients with active TB infection or control group. The discrimination performance (assessed by the area under ROC curve) for IL-2 following stimulation with recombinant PE35 and PPE68 between LTBI and patients with active TB were 0.837 (95%CI: 0.72-0.97) and 0.75 (95%CI: 0.63-0.89), respectively. Applying the 12.4 pg/mL cut-off for IL-2 induced by PE35 in the present study population resulted in sensitivity of 78%, specificity of 78%, PPV of 78% and NPV of 100%. In addition, a sensitivity of 81%, specificity of 70%, PPV of 67% and 87% of NPV was reported based on the 4.4 pg/mL cut-off for IL-2 induced by PPE68. In conclusion, peptides of the antigen PE35 and PPE68, absent from commonly used BCG strains, stimulated strong IL-2- positive T cell responses in patients with LTBI. This study confirms IL-2 induced by PE35 and PPE68 as a sensitive and specific biomarker and highlights IL-2 as new promising adjunct markers for discriminating of LTBI and Active TB infection.Keywords: IL-2, PE35, PPE68, tuberculosis
Procedia PDF Downloads 4093681 Cr Induced Magnetization in Zinc-Blende ZnO-Based Diluted Magnetic Semiconductors
Authors: Bakhtiar Ul Haq, R. Ahmed, A. Shaari, Mazmira Binti Mohamed, Nisar Ali
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The capability of exploiting the electronic charge and spin properties simultaneously in a single material has made diluted magnetic semiconductors (DMS) remarkable in the field of spintronics. We report the designing of DMS based on zinc-blend ZnO doped with Cr impurity. The full potential linearized augmented plane wave plus local orbital FP-L(APW+lo) method in density functional theory (DFT) has been adapted to carry out these investigations. For treatment of exchange and correlation energy, generalized gradient approximations have been used. Introducing Cr atoms in the matrix of ZnO has induced strong magnetic moment with ferromagnetic ordering at stable ground state. Cr:ZnO was found to favor the short range magnetic interaction that reflect the tendency of Cr clustering. The electronic structure of ZnO is strongly influenced in the presence of Cr impurity atoms where impurity bands appear in the band gap.Keywords: ZnO, density functional theory, diluted agnetic semiconductors, ferromagnetic materials, FP-L(APW+lo)
Procedia PDF Downloads 4253680 Hypolipidemic and Antioxidant Effects of Mycelial Polysaccharides from Calocybe indica in Hyperlipidemic Rats Induced by High-Fat Diet
Authors: Govindan Sudha, Mathumitha Subramaniam, Alamelu Govindasamy, Sasikala Gunasekaran
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The aim of this study was to investigate the protective effect of Hypsizygus ulmarius polysaccharides (HUP) on reducing oxidative stress, cognitive impairment and neurotoxicity in D-galactose induced aging mice. Mice were subcutaneously injected with D-galactose (150 mg/kg per day) for 6 weeks and were administered HUP simultaneously. Aged mice receiving vitamin E (100 mg/kg) served as positive control. Chronic administration of D-galactose significantly impaired cognitive performance oxidative defence and mitochondrial enzymes activities as compared to control group. The results showed that HUP (200 and 400 mg/kg) treatment significantly improved the learning and memory ability in Morris water maze test. Biochemical examination revealed that HUP significantly increased the decreased activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), mitochondrial enzymes-NADH dehydrogenase, malate dehydrogenase (MDH), isocitrate dehydrogenase (ICDH), Na+K+, Ca2+, Mg2+ATPase activities, elevated the lowered total anti-oxidation capability (TAOC), glutathione (GSH), vitamin C and decreased the raised acetylcholinesterase (AChE) activities, malondialdehyde (MDA), hydroperoxide (HPO), protein carbonyls (PCO), advanced oxidation protein products (AOPP) levels in brain of aging mice induced by D-gal in a dose-dependent manner. In conclusion, present study highlights the potential role of HUP against D-galactose induced cognitive impairment, biochemical and mitochondrial dysfunction in mice. In vitro studies on the effect of HUP on scavenging DPPH, ABTS, DMPD, OH radicals, reducing power, B-carotene bleaching and lipid peroxidation inhibition confirmed the free radical scavenging and antioxidant activity of HUP. The results suggest that HUP possesses anti-aging efficacy and may have potential in treatment of neurodegenerative diseases.Keywords: aging, antioxidants, mushroom, neurotoxicity
Procedia PDF Downloads 5293679 Hypoglycaemic and Hypolipidemic Activity of Cassia occidentalis Linn. Stem Bark Extract in Streptozotocin Induced Diabetes
Authors: Manjusha Choudhary
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Objective: Cassia occidentalis Linn. belongs to Family Caesalpiniaceae is a common weed scattered from the foothills of Himalayas to West Bengal, South India, Burma, and Sri Lanka. It is used widely in folklore medicine in India as laxative, expectorant, analgesic, anti-malarial, hepatoprotective, relaxant, anti-inflammatory and antidiabetic. The present study was carried out to investigate the hypoglycaemic and hypolipidemic activities of ethanolic extract of Cassia occidentalis stem bark. Methods: Stem bark extract of Cassia occidentalis (SBCO) was administered orally at 250 and 500 mg/kg doses to normal and streptozotocin (STZ) induced type-2 diabetic mice. Various parameters like fasting blood glucose (FBG) level, serum cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides (TG), total protein, urea, creatinine, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) levels and physical parameters like change in body weight, food intake, water intake were performed for the evaluation of antidiabetic effects. Results: Both the doses of extract caused a marked decrease in FBG levels in STZ induced type 2 diabetic mice. Administration of SBCO led to the decrease in the blood glucose, food intake, water intake, organ weight, SGOT, SGPT levels with significant value and increased the levels of TG, HDL cholesterol, creatinine, cholesterol, total protein with a significant value (p < 0.05-0.01). The decrease in body weight induced by STZ was restored to normal with a significant value (p < 0.01) at both doses. Conclusion: Present study reveals that SBCO possess potent hypoglycaemic and hypolipidemic activities and supports the folklore use of the stem bark of plant as antidiabetic agent.Keywords: Cassia occidentalis, diabetes, folklore, herbs, hypoglycemia, streptozotocin
Procedia PDF Downloads 4063678 Hyaluronan and Hyaluronan-Associated Genes in Human CD8 T Cells
Authors: Emily Schlebes, Christian Hundhausen, Jens W. Fischer
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The glycosaminoglycan hyaluronan (HA) is a major component of the extracellular matrix, typically produced by fibroblasts of the connective tissue but also by immune cells. Here, we investigated the capacity of human peripheral blood CD8 T cells from healthy donors to produce HA and to express HA receptors as well as HA degrading enzymes. Further, we evaluated the effect of pharmacological HA inhibition on CD8 T cell function. Using immunocytochemistry together with quantitative PCR analysis, we found that HA synthesis is rapidly induced upon antibody-induced T cell receptor (TCR) activation and almost exclusively mediated by HA synthase 3 (HAS3). TCR activation also resulted in the upregulation of HA receptors CD44, hyaluronan-mediated motility receptor (HMMR), and layilin (LAYN), although kinetics and strength of expression varied greatly between subjects. The HA-degrading enzymes HYAL1 and HYAL2 were detected at low levels and induced by cell activation in some individuals. Interestingly, expression of HAS3, HA receptors, and hyaluronidases were modulated by the proinflammatory cytokines IL-6 and IL-1bβ in most subjects. To assess the functional role of HA in CD8 T cells, we performed carboxyfluorescein succinimidyl ester (CFSE) based proliferation assays and cytokine analysis in the presence of the HA inhibitor 4- Methylumbelliferone (4-MU). Despite significant inter-individual variation with regard to the effective dose, 4-MU resulted in the inhibition of CD8 T cell proliferation and reduced release of TNF-α and IFN-γ. Collectively, these data demonstrate that human CD8 T cells respond to TCR stimulation with a synthesis of HA and expression of HA-related genes. They further suggest that HA inhibition may be helpful in interfering with pathogenic T cell activation in human disease.Keywords: CD8 T cells, extracellular matrix, hyaluronan, hyaluronan synthase 3
Procedia PDF Downloads 993677 Effects of G-jitter Combined with Heat and Mass Transfer by Mixed Convection MHD Flow of Maxwell Fluid in a Porous Space
Authors: Faisal Salah, Z. A. Aziz, K. K. Viswanathan
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In this article, the effects of g-jitter induced and combined with heat and mass transfer by mixed convection of MHD Maxwell fluid in microgravity situation is investigated for a simple system. This system consists of two heated vertical parallel infinite flat plates held at constant but different temperatures and concentrations. By using modified Darcy’s law, the equations governing the flow are modelled. These equations are solved analytically for the induced velocity, temperature and concentration distributions. Many interesting available results in the relevant literature (i.e. Newtonian fluid) is obtained as the special case of the present general analysis. Finally, the graphical results for the velocity profile of the oscillating flow in the channel are presented and discussed for different values of the material constants.Keywords: g-jitter, heat and mass transfer, mixed convection, Maxwell fluid, porous medium
Procedia PDF Downloads 4923676 A Wall Law for Two-Phase Turbulent Boundary Layers
Authors: Dhahri Maher, Aouinet Hana
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The presence of bubbles in the boundary layer introduces corrections into the log law, which must be taken into account. In this work, a logarithmic wall law was presented for bubbly two phase flows. The wall law presented in this work was based on the postulation of additional turbulent viscosity associated with bubble wakes in the boundary layer. The presented wall law contained empirical constant accounting both for shear induced turbulence interaction and for non-linearity of bubble. This constant was deduced from experimental data. The wall friction prediction achieved with the wall law was compared to the experimental data, in the case of a turbulent boundary layer developing on a vertical flat plate in the presence of millimetric bubbles. A very good agreement between experimental and numerical wall friction prediction was verified. The agreement was especially noticeable for the low void fraction when bubble induced turbulence plays a significant role.Keywords: bubbly flows, log law, boundary layer, CFD
Procedia PDF Downloads 2783675 Protective Potential of Hyperhalophilic Diatoms Extract Against Lead Induced Oxidative Stress in Rats and Human HepG2 and HEK293 Cells Line
Authors: Wassim Guermazi, Saoussan Boukhris, Neila Annabi Trabelsi, Tarek Rebai, Alya Sellami-Kamoun, Habib Ayadi
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This work investigates the protective effects of the microalga Halamphora sp. extract (H. Ext) as a natural product on lead-intoxicated liver and kidney human cells in vitro and in vivo on rats wistar. HepG2 cells line derived from human hepatocellular carcinoma and HEK293 cells line derived from human embryonic kidney were used for the in vitro study. The analysis of the fatty acids methyl esters of the extract was performed by a GC/MS. Four groups of rats, each of which was composed of six animals, were used for the in vivo experiment. The pretreatment of HepG2 and HEK293 cells line with the extract (100 µg mL-1) significantly (p < 0.05) protected against cytotoxicity induced by lead exposure. In vivo, the biochemical parameters in serum, namely malondialdehyde level (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities, were measured in supernatants of organ homogenates. H. Ext was found to be rich in fatty acids, essentially palmitic and palmitoleic accounting respectively 29.46% and 42.07% of total fatty acids. Both in vitro and in vivo, the co-treatment with H. Ext allowed the protection of the liver and kidney cells structure, as well as the significant preservation of normal antioxidant and biochemical parameters in rats. Halamphora extract rich in fatty acids has been proven to be effective in protection against Pb-induced toxicity.Keywords: microalga extract, human cells line, fatty acid, lead exposure, oxidative stress, rats
Procedia PDF Downloads 883674 TNF Receptor-Associated Factor 6 (TRAF6) Mediating the Angiotensin-Induced Non-Canonical TGFβ Pathway Activation and Differentiation of c-kit+ Cardiac Stem Cells
Authors: Qing Cao, Fei Wang, Yu-Qiang Wang, Li-Ya Huang, Tian-Tian Sang, Shu-Yan Chen
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Aims: TNF Receptor-Associated Factor 6 (TRAF6) acts as a multifunctional regulator of the Transforming Growth Factor (TGF)-β signaling pathway, and mediates Smad-independent JNK and p38 activation via TGF-β. This study was performed to test the hypothesis that TGF-β/TRAF6 is essential for angiotensin-II (Ang II)-induced differentiation of rat c-kit+ Cardiac Stem Cells (CSCs). Methods and Results: c-kit+ CSCs were isolated from neonatal Sprague Dawley (SD) rats, and their c-kit status was confirmed with immunofluorescence staining. A TGF-β type I receptor inhibitor (SB431542) or the small interfering RNA (siRNA)-mediated knockdown of TRAF6 were used to investigate the role of TRAF6 in TGF-β signaling. Rescue of TRAF6 siRNA transfected cells with a 3'UTR deleted siRNA insensitive construct was conducted to rule out the off target effects of the siRNA. TRAF6 dominant negative (TRAF6DN) vector was constructed and used to infect c-kit+ CSCs, and western blotting was used to assess the expression of TRAF6, JNK, p38, cardiac-specific proteins, and Wnt signaling proteins. Physical interactions between TRAF6 and TGFβ receptors were studied by coimmunoprecipitation. Cardiac differentiation was suppressed in the absence of TRAF6. Forced expression of TRAF6 enhanced the expression of TGF-β-activated kinase1 (TAK1), and inhibited Wnt signaling. Furthermore, TRAF6 increased the expression of cardiac-specific proteins (cTnT and Cx-43) but inhibited the expression of Wnt3a. Conclusions: Our data suggest that TRAF6 plays an important role in Ang II induced differentiation of c-kit+ CSCs via the non-canonical signaling pathway.Keywords: cardiac stem cells, differentiation, TGF-β, TRAF6, ubiquitination, Wnt
Procedia PDF Downloads 4013673 Use of Curcumin in Radiochemotherapy Induced Oral Mucositis Patients: A Control Trial Study
Authors: Shivayogi Charantimath
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Radiotherapy and chemotherapy are effective for treating malignancies but are associated with side effects like oral mucositis. Chlorhexidine gluconate is one of the most commonly used mouthwash in prevention of signs and symptoms of mucositis. Evidence shows that chlorhexidine gluconate has side effects in terms of colonization of bacteria, bad breadth and less healing properties. Thus, it is essential to find a suitable alternative therapy which is more effective with minimal side effects. Curcumin, an extract of turmeric is gradually being studied for its wide-ranging therapeutic properties such as antioxidant, analgesic, anti-inflammatory, antitumor, antimicrobial, antiseptic, chemo sensitizing and radio sensitizing properties. The present study was conducted to evaluate the efficacy and safety of topical curcumin gel on radio-chemotherapy induced oral mucositis in cancer patients. The aim of the study is to evaluate the efficacy and safety of curcumin gel in the management of oral mucositis in cancer patients undergoing radio chemotherapy and compare with chlorhexidine. The study was conducted in K.L.E. Society’s Belgaum cancer hospital. 40 oral cancer patients undergoing the radiochemotheraphy with oral mucositis was selected and randomly divided into two groups of 20 each. The study group A [20 patients] was advised Cure next gel for 2 weeks. The control group B [20 patients] was advised chlorhexidine gel for 2 weeks. The NRS, Oral Mucositis Assessment scale and WHO mucositis scale were used to determine the grading. The results obtained were calculated by using SPSS 20 software. The comparison of grading was done by applying Mann-Whitney U test and intergroup comparison was calculated by Wilcoxon matched pairs test. The NRS scores observed from baseline to 1st and 2nd week follow up in both the group showed significant difference. The percentage of change in erythema in respect to group A was 63.3% for first week and for second week, changes were 100.0% with p = 0.0003. The changes in Group A in respect to erythema was 34.6% for 1st week and 57.7% in second week. The intergroup comparison was significant with p value of 0.0048 and 0.0006 in relation to group A and group B respectively. The size of the ulcer score was measured which showed 35.5% [P=0.0010] of change in Group A for 1st and 2nd week showed totally reduction i.e. 103.4% [P=0.0001]. Group B showed 24.7% change from baseline to 1st week and 53.6% for 2nd week follow up. The intergroup comparison with Wilcoxon matched pair test was significant with p=0.0001 in group A. The result obtained by WHO mucositis score in respect to group A shows 29.6% [p=0.0004] change in first week and 75.0% [p=0.0180] change in second week which is highly significant in comparison to group B. Group B showed minimum changes i.e. 20.1% in 1st week and 33.3% in 2nd week. The p value with Wilcoxon was significant with 0.0025 in Group A for 1st week follow up and 0.000 for 2nd week follow up. Curcumin gel appears to an effective and safer alternative to chlorhexidine gel in treatment of oral mucositis.Keywords: curcumin, chemotheraphy, mucositis, radiotheraphy
Procedia PDF Downloads 3513672 Comparative Study between Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Ulcerative Colitis Induced Experimentally in Rats
Authors: Azza H. El-Medany, Hanan H. Hagar, Jamila H. El-Medany
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Ulcerative colitis (UC) is one of chronic inflammatory diseases primarily affecting colon with unknown etiology. Some researches papers mentioned the possibility of the use of drugs that affect the angiotensin II in reducing the complication of ulcerative colitis. The aim of the present study is to evaluate the potential protective and therapeutic effects of captopril and valsartan on ulcerative colitis induced experimentally in rats using acetic acid. The results were assessed by histological assessment of colonic tissues and measurement of malondialdehyde (MDA), tumor necrosis factor (TNF-α), transforming growth factor (TGF-1B), angiotensin converting enzyme (ACE), reduced glutathione (GSH) and platelet activating factor (PAF) levels in colonic tissues. Oral pre-treatment with captopril or valsartan in a dose of 30 mgkg-1 body weight for 2 weeks before induction of colitis (prophylactic groups) and continuously for 2 weeks after induction (therapeutic groups) significantly reduce MDA, TNF-α, PAF, TGF-1B and ACE levels in colonic tissues as compared to acetic acid control group. Also, a significant increase in GSH level was observed in colonic tissues. Captopril and valsartan attenuated the macroscopic and microscopic colonic damage induced by acetic acid. These results suggest that either captopril or valsartan may be effective as prophylactic or treatment of UC through inhibition of ACE and scavenging effect on oxygen-derived free radicals.Keywords: captopril, valsartan, angiotensin converting enzyme, reduced glutathione, tumor necrosis factor
Procedia PDF Downloads 2693671 Pistacia Lentiscus: A Plant With Multiple Virtues for Human Health
Authors: Djebbar Atmani, Aghiles Karim Aissat, Nadjet Debbache-Benaida, Nassima Chaher-Bazizi, Dina Atmani-Kilani, Meriem Rahmani-Berboucha, Naima Saidene, Malika Benloukil, Lila Azib
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Medicinal plants are believed to be an important source for the discovery of potential antioxidant, anti-inflammatory and anti-diabetic substances. The present study was designed to investigate the neuroprotective, anti-inflammatory, anti-diabetic and anti-hyperuricemic potential of Pistacia lentiscus, as well as the identification of active compounds. The antioxidant potential of plant extracts against known radicals was measured using various standard in vitro methods. Anti-inflammatory activity was determined using the paw edema model in mice and by measuring the secretion of the pro-inflammatory cytokine, whereas the anti-diabetic effect was assessed in vivo on streptozotocin-induced diabetic rats and in vitro by inhibition of alpha-amylase. The anti-hyperuricemic activity was evaluated using the xanthine oxidase assay, whereas neuroprotective activity was investigated using an Aluminum-induced toxicity test. Pistacia lentiscus extracts and fractions exhibited high scavenging capacity against DPPH, NO. and ABTS+ radicals in a dose-dependent manner and restored blood glucose levels, in vivo, to normal values, in agreement with the in vitro anti-diabetic effect. Oral administration of plant extracts significantly decreased carrageenan-induced mice paw oedema, similar to the standard drug, diclofenac, was effective in reducing IL-1β levels in cell culture and induced a significant increase in urinary volume in mice, associated to a promising anti-hyperuricemic activity. Plant extracts showed good neuroprotection and restoration of cognitive functions in mice. HPLC-MS and NMR analyses allowed the identification of known and new phenolic compounds that could be responsible for the observed activities. Therefore, Pistacia lentiscus could be beneficial in the treatment of inflammatory conditions and diabetes complications and the enhancement of cognitive functions.Keywords: Pistacia lentiscus, anti-inflammatory, antidiabetic, flavanols, neuroprotective
Procedia PDF Downloads 1363670 Infra Red Laser Induced Ablation of Graphene Based Polymer Nanocomposites
Authors: Jadranka Blazhevska Gilev
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IR laser-induced ablation of poly(butylacrylate-methylmethacrylate/hydroxyl ethyl methacrylate)/reduced graphene oxide (p(BA/MMA/HEMA)/rGO) was examined with 0.5, 0.75 and 1 wt% reduced graphene oxide content in relation to polymer. The irradiation was performed with TEA (transversely excited atmosphere) CO₂ laser using incident fluence of 15-20 J/cm², repetition frequency of 1 Hz, in an evacuated (10-3 Pa) Pyrex spherical vessel. Thin deposited nanocomposites films with large specific area were obtained using different substrates. The properties of the films deposited on these substrates were evaluated by TGA, FTIR, (Thermogravimetric analysis, Fourier Transformation Infrared) Raman spectroscopy and SEM microscopy. Homogeneous distribution of graphene sheets was observed from the SEM images, making polymer/rGO deposit an ideal candidate for SERS application. SERS measurements were performed using Rhodamine 6G as probe molecule on the substrate Ag/p(BA/MMA/HEMA)/rGO.Keywords: laser ablation, reduced graphene oxide, polymer/rGO nanocomposites, thin deposited film
Procedia PDF Downloads 1983669 Analysis of Mechanotransduction-Induced Microalgae under Direct Membrane Distortion
Authors: Myung Kwon Cho, Seul Ki Min, Gwang Heum Yoon, Jung Hyun Joo, Sang Jun Sim, Hwa Sung Shin
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Mechanotransduction is a mechanism that external mechanical stimulation is converted to biochemical activity in the cell. When applying this mechanism to the unicellular green algae Chlamydomonas reinhardtii, the dramatic result that the accumulation of intracellular lipid was up to 60% of dry weight basis occurred. Furthermore, various variations in cellular physiology occurred, but there is a lack of the development of the system and related research for applying that technology to control the mechanical stress and facilitate molecular analyses. In this study, applying a mechanical stress to microalgae, the microfluidic device system that finely induced direct membrane distortion of microalgae. Cellular membrane distortion led to deflagellation, calcium influx and lipid accumulation in microalgae. In conclusion, cytological studies such as mechanotransduction can be actualized by using this system and membrane distortion is a promising inducer for biodiesel production.Keywords: mechanotransduction, microalgae, membrane distortion, biodiesel
Procedia PDF Downloads 3233668 Effects of Channel Orientation on Heat Transfer in a Rotating Rectangular Channel with Jet Impingement Cooling and Film Coolant Extraction
Authors: Hua Li, Hongwu Deng
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The turbine blade's leading edge is usually cooled by jet impingement cooling technology due to the heaviest heat load. For a rotating turbine blade, however, the channel orientation (β, the angle between the jet direction and the rotating plane) could play an important role in influencing the flow field and heat transfer. Therefore, in this work, the effects of channel orientation (from 90° to 180°) on heat transfer in a jet impingement cooling channel are experimentally investigated. Furthermore, the investigations are conducted under an isothermal boundary condition. Both the jet-to-target surface distance and jet-to-jet spacing are three times the jet hole diameter. The jet Reynolds number is 5,000, and the maximum jet rotation number reaches 0.24. The results show that the rotation-induced variations of heat transfer are different in each channel orientation. In the cases of 90°≤β≤135°, a vortex generated in the low-radius region of the supply channel changes the mass-flowrate distribution in each jet hole. Therefore, the heat transfer in the low-radius region decreases with the rotation number, whereas the heat transfer in the high-radius region increases, indicating that a larger temperature gradient in the radial direction could appear in the turbine blade's leading edge. When 135°<β≤180°; however, the heat transfer of the entire stagnant zone decreases with the rotation number. The rotation-induced jet deflection is the primary factor that weakens the heat transfer, and jets cannot reach the target surface at high rotation numbers. For the downstream regions, however, the heat transfer is enhanced by 50%-80% in every channel orientation because the dead zone is broken by the rotation-induced secondary flow in the impingement channel.Keywords: heat transfer, jet impingement cooling, channel orientation, high rotation number, isothermal boundary
Procedia PDF Downloads 1053667 Cognitive Rehabilitation in Schizophrenia: A Review of the Indian Scenario
Authors: Garima Joshi, Pratap Sharan, V. Sreenivas, Nand Kumar, Kameshwar Prasad, Ashima N. Wadhawan
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Schizophrenia is a debilitating disorder and is marked by cognitive impairment, which deleteriously impacts the social and professional functioning along with the quality of life of the patients and the caregivers. Often the cognitive symptoms are in their prodromal state and worsen as the illness progresses; they have proven to have a good predictive value for the prognosis of the illness. It has been shown that intensive cognitive rehabilitation (CR) leads to improvements in the healthy as well as cognitively-impaired subjects. As the majority of population in India falls in the lower to middle socio-economic status and have low education levels, using the existing packages, a majority of which are developed in the West, for cognitive rehabilitation becomes difficult. The use of technology is also restricted due to the high costs involved and the limited availability and familiarity with computers and other devices, which pose as an impedance for continued therapy. Cognitive rehabilitation in India uses a plethora of retraining methods for the patients with schizophrenia targeting the functions of attention, information processing, executive functions, learning and memory, and comprehension along with Social Cognition. Psychologists often have to follow an integrative therapy approach involving social skills training, family therapy and psychoeducation in order to maintain the gains from the cognitive rehabilitation in the long run. This paper reviews the methodologies and cognitive retaining programs used in India. It attempts to elucidate the evolution and development of methodologies used, from traditional paper-pencil based retraining to more sophisticated neuroscience-informed techniques in cognitive rehabilitation of deficits in schizophrenia as home-based or supervised and guided programs for cognitive rehabilitation.Keywords: schizophrenia, cognitive rehabilitation, neuropsychological interventions, integrated approached to rehabilitation
Procedia PDF Downloads 3633666 Design, Development, and Implementation of the Pediatric Physical Therapy Senior Clinical Internship Telerehabilitation Program of de la Salle Medical and Health Sciences Institute: The Pandemic Impetus
Authors: Ma. Cecilia D. Licuan
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The pandemic situation continues to affect the lives of many people, including children with disabilities and their families, globally, especially in developing countries like the Philippines. The operations of health programs, industries, and economic sectors, as well as academic training institutions, are still challenged in terms of operations and delivery of services. The academic community of the Physical Therapy program is not spared by this circumstance. The restriction posted by the quarantine policies nearly terminated the onsite delivery of training programs for the senior internship level, which challenged the academic institutions to implement flexible learning programs to ensure the continuity of the instructional and learning processes with full consideration of safety and compliance to health protocols. This study aimed to develop a benchmark model that can be used by tertiary-level health institutions in the implementation of the Pediatric Senior Clinical Internship Training Program using Telerehabilitation. It is a descriptive-qualitative paper that utilized documentary analysis and focused on explaining the design, development, and implementation processes used by De La Salle Medical and Health Sciences Institute – College of Rehabilitation Sciences (DLSMHSI-CRS) Physical Therapy Department in its Pediatric Cluster Senior Clinical Internship Training Program covering the pandemic years spanning from the academic year 2020- 2021 to present anchored on needs analysis based on documentary reviews. Results of the study yielded the determination of the Pediatric Telerehabilitation Model; declaration of developed training program outcomes and thrusts and content; explanation of the process integral to the training program’s pedagogy in implementation; and the evaluation procedures conducted for the program. Since the study did not involve human participants, ethical considerations on the use of documents for review were done upon the endorsement of the management of the DLSMHSI-CRS to conduct the study. This paper presents the big picture of how a tertiary-level health sciences institution in the Philippines embraced the senior clinical internship challenges through the operations of its telerehabilitation program. It specifically presents the design, development and implementation processes used by De La Salle Medical and Health Sciences Institute – College of Rehabilitation Sciences Physical Therapy Department in its Pediatric Cluster Senior Clinical Internship Training Program, which can serve as a benchmark model for other institutions as they continue to serve their stakeholders amidst the pandemic.Keywords: pediatric physical therapy, telerehabilitation, clinical internship, pandemic
Procedia PDF Downloads 1243665 Evaluation of Activity of Anacyclus Pyrethrum Methanolic Extract on Acute Inflammation Induced in Rats
Authors: Dalila Bouamra, Chekib Arslane Baki, Abdelhamid Bouchebour, Fatiha Koussa, Amel Benamara, Seoussen Kada
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The activity of methanolic extract from Anacyclus pyrethrum was evaluated using λ-carrageenan 1% induced paw edema in Wistar Albinos rats. The oral administration of 200 mg/kg, 400 mg/kg and 600 mg/kg, body weight of methanolic extract, one hour before induction of inflammation, exerted a significant inhibition effect of 47%, 57% and 62% respectively after 4h λ-carrageenan treatment and highly significant inhibition effect of 57%, 66% and 75% respectively after 8h λ-carrageenan treatment, compared to non treated group (100%) and that treated with aspirin, a standard anti-inflammatory drug. On the other hand, the effect of the plant extract on stomach was macroscopically and microscopically studied. The plant extract has an impact on the loss ratio of granulocytes that have invaded the stomach after a period of inflammation at a dose of 600 mg/kg body weight.Keywords: inflammation, Anacyclus pyrethrum, gastritis, Wistar Albinos rats
Procedia PDF Downloads 4873664 Dynamic Response Analyses for Human-Induced Lateral Vibration on Congested Pedestrian Bridges
Authors: M. Yoneda
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In this paper, a lateral walking design force per person is proposed and compared with Imperial College test results. Numerical simulations considering the proposed walking design force which is incorporated into the neural-oscillator model are carried out placing much emphasis on the synchronization (the lock-in phenomenon) for a pedestrian bridge model with the span length of 50 m. Numerical analyses are also conducted for an existing pedestrian suspension bridge. As compared with full scale measurements for this suspension bridge, it is confirmed that the analytical method based on the neural-oscillator model might be one of the useful ways to explain the synchronization (the lock-in phenomenon) of pedestrians being on the bridge.Keywords: pedestrian bridge, human-induced lateral vibration, neural-oscillator, full scale measurement, dynamic response analysis
Procedia PDF Downloads 2013663 Antiproliferative and Apoptotic Effects of an Enantiomerically Pure β-Dipeptide Derivative through PI3K/Akt-Dependent and -Independent Pathways in Human Hormone-Refractory Prostate Cancer Cells
Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh
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Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt
Procedia PDF Downloads 2823662 Histological Study on the Effect of Bone Marrow Transplantation Combined with Curcumin on Pancreatic Regeneration in Streptozotocin Induced Diabetic Rats
Authors: Manal M. Shehata, Kawther M. Abdel-Hamid, Nashwa A. Mohamed, Marwa H. Bakr, Maged S. Mahmoud, Hala M. Elbadre
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Introduction: The worldwide rapid increase in diabetes poses a significant challenge to current therapeutic approaches. Therapeutic utility of bone marrow transplantation in diabetes is an attractive approach. However, the oxidative stress generated by hyperglycemia may hinder β-cell regeneration. Curcumin, is a dietary spice with antioxidant activity. Aim of work: The present study was undertaken to investigate the therapeutic potential of curcumin, bone marrow transplantation, and their combined effects in the reversal of experimental diabetes. Material and Methods: Fifty adult male healthy albino rats were included in the present study.They were divided into two groups: Group І: (control group) included 10 rats. Group П: (diabetic group): included 40 rats. Diabetes was induced by single intraperitoneal injection of streptozotocin (STZ). Group II will be further subdivided into four groups (10 rats for each): Group II-a (diabetic control). Group II-b: rats were received single intraperitoneal injection of bone marrow suspension (un-fractionated bone marrow cells) prepared from rats of the same family. Group II-c: rats were treated with curcumin orally by gastric intubation for 6 weeks. Group II-d: rats were received a combination of single bone marrow transplantation and curcumin for 6 weeks. After 6 weeks, blood glucose, insulin levels were measured and the pancreas from all rats were processed for Histological, Immunohistochemical and morphometric examination. Results: Diabetic group, showed progressive histological changes in the pancreatic islets. Treatment with either curcumin or bone marrow transplantation improved the structure of the islets and reversed streptozotocin-induced hyperglycemia and hypoinsulinemia. Combination of curcumin and bone marrow transplantation elicited more profound alleviation of streptozotocin-induced changes including islet regeneration and insulin secretion. Conclusion: The use of natural antioxidants combined with bone marrow transplantation to induce pancreatic regeneration is a promising strategy in the management of diabetes.Keywords: diabtes, panceatic islets, bone marrow transplantation, curcumin
Procedia PDF Downloads 3863661 Effect of Irradiation on Nano-Indentation Properties and Microstructure of X-750 Ni-Based Superalloy
Authors: Pooyan Changizian, Zhongwen Yao
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The purpose of current study is to make an excellent correlation between mechanical properties and microstructures of ion irradiated X-750 Ni-based superalloy. Towards this end, two different irradiation procedures were carried out, including single Ni ion irradiation and pre-helium implantation with subsequent Ni ion irradiation. Nano-indentation technique was employed to evaluate the mechanical properties of irradiated material. The nano-hardness measurements depict highly different results for two irradiation procedures. Single ion irradiated X-750 shows softening behavior; however, pre-helium implanted specimens present significant hardening compared to the un-irradiated material. Cross-section TEM examination demonstrates that softening is attributed to the γ׳-precipitate instability (disordering/dissolution) which overcomes the hardening effect of irradiation-induced defects. In contrast, the presence of cavities or helium bubbles is probably the main cause for irradiation-induced hardening of helium implanted samples.Keywords: Inconel X-750, nanoindentation, helium bubbles, defects
Procedia PDF Downloads 222