Search results for: creatinine induced nephrotoxicity

Authors: Michalina Aniola, Andrzej Katrusiak

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4,4-Bipyridine is an important compound often used in chemical practice and more recently frequently applied for designing new metal organic framework (MoFs). Here we present a systematic high-pressure study of its hydrobromide salt. 4,4-Bipyridine hydrobromide monohydrate, 44biPyHBrH₂O, at ambient-pressure is orthorhombic, space group P212121 (phase a). Its hydrostatic compression shows that it is stable to 1.32 GPa at least. However, the recrystallization above 0.55 GPa reveals a new hidden b-phase (monoclinic, P21/c). Moreover, when the 44biPyHBrH2O is heated to high temperature the chemical reactions of this compound in methanol solution can be observed. High-pressure experiments were performed using a Merrill-Bassett diamond-anvil cell (DAC), modified by mounting the anvils directly on the steel supports, and X-ray diffraction measurements were carried out on a KUMA and Excalibur diffractometer equipped with an EOS CCD detector. At elevated pressure, the crystal of 44biPyHBrH₂O exhibits several striking and unexpected features. No signs of instability of phase a were detected to 1.32 GPa, while phase b becomes stable at above 0.55 GPa, as evidenced by its recrystallizations. Phases a and b of 44biPyHBrH2O are partly isostructural: their unit-cell dimensions and the arrangement of ions and water molecules are similar. In phase b the HOH-Br- chains double the frequency of their zigzag motifs, compared to phase a, and the 44biPyH+ cations change their conformation. Like in all monosalts of 44biPy determined so far, in phase a the pyridine rings are twisted by about 30 degrees about bond C4-C4 and in phase b they assume energy-unfavorable planar conformation. Another unusual feature of 44biPyHBrH2O is that all unit-cell parameters become longer on the transition from phase a to phase b. Thus the volume drop on the transition to high-pressure phase b totally depends on the shear strain of the lattice. Higher temperature triggers chemical reactions of 44biPyHBrH2O with methanol. When the saturated methanol solution compound precipitated at 0.1 GPa and temperature of 423 K was required to dissolve all the sample, the subsequent slow recrystallization at isochoric conditions resulted in disalt 4,4-bipyridinium dibromide. For the 44biPyHBrH2O sample sealed in the DAC at 0.35 GPa, then dissolved at isochoric conditions at 473 K and recrystallized by slow controlled cooling, a reaction of N,N-dimethylation took place. It is characteristic that in both high-pressure reactions of 44biPyHBrH₂O the unsolvated disalt products were formed and that free base 44biPy and H₂O remained in the solution. The observed reactions indicate that high pressure destabilized ambient-pressure salts and favors new products. Further studies on pressure-induced reactions are carried out in order to better understand the structural preferences induced by pressure.

Keywords: conformation, high-pressure, negative area compressibility, polymorphism

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Authors: Umer Malik, David Armstrong, Mark Ashworth, Alex Dregan, Veline L'Esperance, Lucy McDonnell, Mariam Molokhia, Patrick White

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Introduction: The microbiota lining epithelial surfaces is thought to play an important role in many human physiological functions including defense against pathogens and modulation of immune response. The microbiota is susceptible to disruption from external influences such as exposure to antibiotic medication. It is thought that antibiotic-induced disruption of the microbiota could predispose to pathogen overgrowth and invasion. We hypothesized that antibiotic use would be associated with increased risk of future infections. We carried out a systematic review of evidence of associations between antibiotic use and subsequent risk of community-acquired infections. Methods: We conducted a review of the literature for observational studies assessing the association between antibiotic use and subsequent community-acquired infection. Eligible studies were published before April 29th, 2016. We searched MEDLINE, EMBASE, and Web of Science and screened titles and abstracts using a predefined search strategy. Infections caused by Clostridium difficile, drug-resistant organisms and fungal organisms were excluded as their association with prior antibiotic use has been examined in previous systematic reviews. Results: Eighteen out of 21,518 retrieved studies met the inclusion criteria. The association between past antibiotic exposure and subsequent increased risk of infection was reported in 16 studies, including one study on Campylobacter jejuni infection (Odds Ratio [OR] 3.3), two on typhoid fever (ORs 5.7 and 12.2), one on Staphylococcus aureus skin infection (OR 2.9), one on invasive pneumococcal disease (OR 1.57), one on recurrent furunculosis (OR 16.6), one on recurrent boils and abscesses (Risk ratio 1.4), one on upper respiratory tract infection (OR 2.3) and urinary tract infection (OR 1.1), one on invasive Haemophilus influenzae type b (Hib) infection (OR 1.51), one on infectious mastitis (OR 5.38), one on meningitis (OR 2.04) and five on Salmonella enteric infection (ORs 1.4, 1.59, 1.9, 2.3 and 3.8). The effect size in three studies on Salmonella enteric infection was of marginal statistical significance. A further two studies on Salmonella infection did not demonstrate a statistically significant association between prior antibiotic exposure and subsequent infection. Conclusion: We have found an association between past antibiotic exposure and subsequent risk of a diverse range of infections in the community setting. Our findings provide evidence to support the hypothesis that prior antibiotic usage may predispose to future infection risk, possibly through antibiotic-induced alteration of the microbiota. The findings add further weight to calls to minimize inappropriate antibiotic prescriptions.

Keywords: antibiotic, infection, risk factor, side effect

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Authors: Osman Adiguzel

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Shape memory effect is a peculiar property exhibited by certain alloy systems and based on martensitic transformation, and shape memory properties are closely related to the microstructures of the material. Shape memory effect is linked with martensitic transformation, which is a solid state phase transformation and occurs with the cooperative movement of atoms by means of lattice invariant shears on cooling from high-temperature parent phase. Lattice twinning and detwinning can be considered as elementary processes activated during the transformation. Thermally induced martensite occurs as martensite variants, in self-accommodating manner and consists of lattice twins. Also, this martensite is called the twinned martensite or multivariant martensite. Deformation of shape memory alloys in martensitic state proceeds through a martensite variant reorientation. The martensite variants turn into the reoriented single variants with deformation, and the reorientation process has great importance for the shape memory behavior. Copper based alloys exhibit this property in metastable β- phase region, which has DO3 –type ordered lattice in ternary case at high temperature, and these structures martensiticaly turn into the layered complex structures with lattice twinning mechanism, on cooling from high temperature parent phase region. The twinning occurs as martensite variants with lattice invariant shears in two opposite directions, <110 > -type directions on the {110}- type plane of austenite matrix. Lattice invariant shear is not uniform in copper based ternary alloys and gives rise to the formation of unusual layered structures, like 3R, 9R, or 18R depending on the stacking sequences on the close-packed planes of the ordered lattice. The unit cell and periodicity are completed through 18 atomic layers in case of 18R-structure. On the other hand, the deformed material recovers the original shape on heating above the austenite finish temperature. Meanwhile, the material returns to the twinned martensite structures (thermally induced martensite structure) in one way (irreversible) shape memory effect on cooling below the martensite finish temperature, whereas the material returns to the detwinned martensite structure (deformed martensite) in two-way (reversible) shape memory effect. Shortly one can say that the microstructural mechanisms, responsible for the shape memory effect are the twinning and detwinning processes as well as martensitic transformation. In the present contribution, x-ray diffraction, transmission electron microscopy (TEM) and differential scanning calorimetry (DSC) studies were carried out on two copper-based ternary alloys, CuZnAl, and CuAlMn.

Keywords: shape memory effect, martensitic transformation, twinning and detwinning, layered structures

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Authors: Ruichong Zhang

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This study proposes a recording-based approach to characterize and quantify earthquake-induced site nonlinearity, exemplified as soil nonlinearity and/or liquefaction. Alternative to Fourier spectral analysis (FSA), the paper introduces time-frequency analysis of earthquake ground motion recordings with the aid of so-called Hilbert-Huang transform (HHT), and offers justification for the HHT in addressing the nonlinear features shown in the recordings. With the use of the 2001 Nisqually earthquake recordings, this study shows that the proposed approach is effective in characterizing site nonlinearity and quantifying the influences in seismic ground responses.

Keywords: site nonlinearity, site amplification, site damping, Hilbert-Huang Transform (HHT), liquefaction, 2001 Nisqually Earthquake

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Authors: Anuruddha Jayasuriya, Thanakorn Pheeraphan

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In this paper, a review of different mathematical models which can be used as prediction tools to assess the time to crack reinforced concrete (RC) due to corrosion is investigated. This investigation leads to an experimental study to validate a selected prediction model. Most of these mathematical models depend upon the mechanical behaviors, chemical behaviors, electrochemical behaviors or geometric aspects of the RC members during a corrosion process. The experimental program is designed to verify the accuracy of a well-selected mathematical model from a rigorous literature study. Fundamentally, the experimental program exemplifies both one-dimensional chloride diffusion using RC squared slab elements of 500 mm by 500 mm and two-dimensional chloride diffusion using RC squared column elements of 225 mm by 225 mm by 500 mm. Each set consists of three water-to-cement ratios (w/c); 0.4, 0.5, 0.6 and two cover depths; 25 mm and 50 mm. 12 mm bars are used for column elements and 16 mm bars are used for slab elements. All the samples are subjected to accelerated chloride corrosion in a chloride bath of 5% (w/w) sodium chloride (NaCl) solution. Based on a pre-screening of different models, it is clear that the well-selected mathematical model had included mechanical properties, chemical and electrochemical properties, nature of corrosion whether it is accelerated or natural, and the amount of porous area that rust products can accommodate before exerting expansive pressure on the surrounding concrete. The experimental results have shown that the selected model for both one-dimensional and two-dimensional chloride diffusion had ±20% and ±10% respective accuracies compared to the experimental output. The half-cell potential readings are also used to see the corrosion probability, and experimental results have shown that the mass loss is proportional to the negative half-cell potential readings that are obtained. Additionally, a statistical analysis is carried out in order to determine the most influential factor that affects the time to corrode the reinforcement in the concrete due to chloride diffusion. The factors considered for this analysis are w/c, bar diameter, and cover depth. The analysis is accomplished by using Minitab statistical software, and it showed that cover depth is the significant effect on the time to crack the concrete from chloride induced corrosion than other factors considered. Thus, the time predictions can be illustrated through the selected mathematical model as it covers a wide range of factors affecting the corrosion process, and it can be used to predetermine the durability concern of RC structures that are vulnerable to chloride exposure. And eventually, it is further concluded that cover thickness plays a vital role in durability in terms of chloride diffusion.

Keywords: accelerated corrosion, chloride diffusion, corrosion cracks, passivation layer, reinforcement corrosion

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Authors: M. A. Sohaly, M. A. Elfouly

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Parkinson's disease (PD) is a heterogeneous movement disorder that often appears in the elderly. PD is induced by a loss of dopamine secretion. Some drugs increase the secretion of dopamine. In this paper, we will simply study the stability of PD models as a nonlinear delay differential equation. After a period of taking drugs, these act as positive feedback and increase the tremors of patients, and then, the differential equation has positive coefficients and the system is unstable under these conditions. We will present a set of suggested modifications to make the system more compatible with the biodynamic system. When giving a set of numerical examples, this research paper is concerned with the mathematical analysis, and no clinical data have been used.

Keywords: Parkinson's disease, stability, simulation, two delay differential equation

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Authors: Xi Chen, King-Yip Cheng

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Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

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Authors: E. Ramprasath, P. Manojkumar, P. Veena

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Proposed paper dealt with the modelling and analysis of induction motor based on the mathematical expression using the graphical programming environment of Laboratory Virtual Instrument Engineering Workbench (LabVIEW). Induction motor modelling with the mathematical expression enables the motor to be simulated with the various required parameters. Owing to the invention of variable speed drives study about the induction motor characteristics became complex.In this simulation motor internal parameter such as stator resistance and reactance, rotor resistance and reactance, phase voltage, frequency and losses will be given as input. By varying the speed of motor corresponding parameters can be obtained they are input power, output power, efficiency, torque induced, slip and current.

Keywords: induction motor, LabVIEW software, modelling and analysi, electrical and mechanical characteristics of motor

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Authors: Iulianna Taritsa, Kuldeep Neote, Eric Fossel

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Lysosome-induced immunogenic cell death (LIICD) is a powerful mechanism of targeting cancer cells that kills circulating malignant cells and primes the host’s immune cells against future remission. Current immunotherapies for cancer are limited in preventing recurrence – a gap that can be bridged by training the immune system to recognize cancer neoantigens. Lysosomal leakage can be induced therapeutically to traffic antigens from dying cells to dendritic cells, which can later present those tumorigenic antigens to T cells. Previous research has shown that oxidative agents administered in the tumor microenvironment can initiate LIICD. We generated a fusion protein between an oxidative agent known as xanthine oxidase (XO) and a mini-antibody specific for EGFR/HER2-sensitive breast tumor cells. The anti-EGFR single domain antibody fragment is uniquely sourced from llama, which is functional without the presence of a light chain. These llama micro-antibodies have been shown to be better able to penetrate tissues and have improved physicochemical stability as compared to traditional monoclonal antibodies. We demonstrate that the fusion protein created is stable and can induce early markers of immunogenic cell death in an in vitro human breast cancer cell line (SkBr3). Specifically, we measured overall cell death, as well as surface-expressed calreticulin, extracellular ATP release, and HMGB1 production. These markers are consensus indicators of ICD. Flow cytometry, luminescence assays, and ELISA were used respectively to quantify biomarker levels between treated versus untreated cells. We also included a positive control group of SkBr3 cells dosed with doxorubicin (a known inducer of LIICD) and a negative control dosed with cisplatin (a known inducer of cell death, but not of the immunogenic variety). We looked at each marker at various time points after cancer cells were treated with the XO/antibody fusion protein, doxorubicin, and cisplatin. Upregulated biomarkers after treatment with the fusion protein indicate an immunogenic response. We thus show the potential for this fusion protein to induce an anticancer effect paired with an adaptive immune response against EGFR/HER2+ cells. Our research in human cell lines here provides evidence for the success of the same therapeutic method for patients and serves as the gateway to developing a new treatment approach against breast cancer.

Keywords: apoptosis, breast cancer, immunogenic cell death, lysosome

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Authors: Amir H. Farivarrad, Kiarash M. Dolatshahi

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During earthquake events, aftershocks can significantly increase the probability of collapse of buildings, especially for those with induced damages during the mainshock. In this paper, a practical approach is proposed for seismic rehabilitation of mainshock-damaged buildings that can be easily implemented within few days after the mainshock. To show the efficacy of the proposed method, a case study nine story steel moment frame building is chosen which was designed to pre-Northridge codes. The collapse fragility curve for the aftershock is presented for both the retrofitted and non-retrofitted structures. Comparison of the collapse fragility curves shows that the proposed method is indeed applicable to reduce the seismic collapse risk.

Keywords: aftershock, the collapse fragility curve, seismic rehabilitation, seismic retrofitting

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Authors: L. Kučerová, M. Bystrianský, V. Kotěšovec

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Thermo-mechanical processing with various processing parameters was applied to 0.2%C-0.6%Mn-2S%i-0.8%Cr low alloyed high strength steel. The aim of the processing was to achieve the microstructures typical for transformation induced plasticity (TRIP) steels. Thermo-mechanical processing used in this work incorporated two or three deformation steps. The deformations were in all the cases carried out during the cooling from soaking temperatures to various bainite hold temperatures. In this way, 4-10% of retained austenite were retained in the final microstructures, consisting further of ferrite, bainite, martensite and pearlite. The complex character of TRIP steel microstructure is responsible for its good strength and ductility. The strengths achieved in this work were in the range of 740 MPa – 836 MPa with ductility A_5mm of 31-41%.

Keywords: pearlite, retained austenite, thermo-mechanical treatment, TRIP steel

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Authors: Safaa S. Hassan, Mohammed H. Elbakry, Safwat A. Mangoura, Zainab M. Omar

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Background: Liver fibrosis is the main reason for increased mortality in chronic liver disease. It has no standard treatment. Antioxidants from a variety of sources are capable of slowing or preventing oxidation of other molecules. Aim: to evaluate the hepatoprotective effect of vit. C, vit. E and gallic acid in comparison to silymarin in the rat model of carbon tetrachloride induced liver fibrosis and their possible mechanisms of action. Material& Methods: A total number of 60 adult male albino rats 160-200gm were divided into six equal groups; received subcutaneous (s.c) injection for 8 weeks. Group I: as control. Group II: received 1.5 mL/kg of CCL4 .Group III: CCL4 and co- treatment with silymarin 100mg/kg p.o. daily. Group IV: CCL4 and co-treatment with vit. C 50mg/kg p.o. daily. Group V: CCL4 and co-treatment with vit. E 200mg/kg. p.o. Group VI: CCL4 and co-treatment with Gallic acid 100mg/kg. p.o. daily. Liver was processed for histological and immunohistochemical examination. Levels of AST, ALT, ALP, reduced GSH, MDA, SOD and hydroxyproline concentration were measured and evaluated statistically. Results: Light and electron microscopic examination of liver of group II exhibited foci of altered cells with dense nuclei and vacuolated, granular cytoplasm, mononuclear cell infiltration in portal areas, profuse collagen fiber deposits were found around portal tract, more intense staining α-SMA-positive cells occupied most of the liver fibrosis tissue, electron lucent areas in the cytoplasm of the hepatocytes, margination of nuclear chromatin. Treatment by any of the antioxidants variably reduced the hepatic structural changes induced by CCL4. Biochemical analysis showed that carbon tetrachloride significantly increased the levels of serum AST, ALT, ALP, hepatic malondialdehyde and hydroxyproline content. Moreover, it decreased the activities of superoxide dismutase and glutathione. Treatment with silymarin, gallic acid, vit. C and vit. E decreased significantly the AST, ALT, and ALP levels in plasma, MDA and hydroxyproline and increased the activities of SOD and glutathione in liver tissue. The effect of administration of CCl4 was improved with the used antioxidants in variable degrees. The most efficient antioxidant was silymarin followed by gallic acid and vit. C then vit. E. It is possibly due to their antioxidant effect, free radical scavenging properties and the reduction of oxidant dependent activation and proliferation of HSCs. Conclusion: So these antioxidants can be a promising drugs candidate for ameliorating liver fibrosis better than the use of the drugs and their side effects.

Keywords: antioxidant, ccl4, gallic acid, liver fibrosis

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Authors: Anupam Saxena, Achin Agrawal, Rishabh Shukla, S. Mandal

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It is quite important that the properties of structural elements do not change significantly before and after cracking, and if they do, it adversely affects the structure. Corrosion in rebars causes cracking in concrete which can lead to the change in properties of beam. In the present study, two RC beams with same flexural strength but with different reinforcement arrangements are considered and modelling of cracks of RC beams has been done at different degrees of corrosion in the case of delamination using boundary conditions of Three Point Bending Test. Finite Element Analysis (FEA) has been done at different degree of corrosion to observe the variation of different parameters like modal frequency, Elasticity and Flexural strength in case of delamination. Also, the comparison between two different RC arrangements is made to conclude which one of them is more suitable.

Keywords: delamination, elasticity, FEA, flexural strength, modal frequency, RC beam

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Authors: Hosein Maghsoudi

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Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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Authors: Juliana V. Pereira, Adriana S. M. Batista, Jefferson P. Nascimento, Clascídia A. Furtado, Luiz O. Faria

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Exposure to ionizing radiation has been found to induce changes in poly(vinylidene fluoride) (PVDF) homopolymers. The high dose gamma irradiation process induces the formation of C=C and C=O bonds in its [CH₂-CF₂]_n main chain. The irradiation also provokes crosslinking and chain scission. All these radio-induced defects lead to changes in the PVDF crystalline structure. As a consequence, it is common to observe a decrease in the melting temperature (T_M) and melting latent heat (L_M) and some changes in its ferroelectric features. We have investigated the possibility of preparing nanocomposites of PVDF with graphene oxide (GO) through the radio-induction of molecular bonds. In this work, we discuss how the gamma radiation interacts with the nanocomposite crystalline structure.

Keywords: gamma irradiation, graphene oxide, nanocomposites, PVDF

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Authors: M. Kalbac, T. Verhagen, K. Drogowska, J. Vejpravova

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One- and two-dimensional carbon nano structures with sp2 hybridization of carbon atoms (single walled carbon nano tubes and graphene) are promising materials in future electronic and spintronics devices due to specific character of their electronic structure. In this paper, we present a comparative study of graphene and single-wall carbon nano tubes by Raman spectro-microscopy in strong magnetic field. This unique method allows to study changes in electronic band structure of the two types of carbon nano structures induced by a strong magnetic field.

Keywords: carbon nano structures, magnetic field, raman spectroscopy, spectro-microscopy

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Authors: Krittapast Dara-Opast, Sureeporn Ruengsangtongkul, Jumreang Tummatorn, Kittipong Chainok, Onrapak Reamtong, Somsak Ruchirawat, Charnsak Thongsornkleeb

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Selective synthesis of gem-dihalo spiroisobenzofuran and spiroisocoumarin can be performed via halogenative double cyclization of methyl 2-(hydroxyalk-1-yn-1-yl) benzoates in the presence of either N-chlorosuccinimide (NCS) or N-bromosuccinimide (NBS) and chlorotrimethylsilane (TMSCl). The combination of NCS and TMSCl led to the generation of electrophilic chlorine in situ, which activated the alkyne functional group of the substrate leading to the cyclization via either 5-exo-dig or 6-endo-dig mode of cyclization to produce the target compounds in moderate yields. The protocol could be carried on a broad scope of substrates under mild conditions (0 °C to rt). The parent compounds showed good antiparasitic activity compared to standard drug albendazole. Further investigation of the scope of the reaction and their antiparasitic activities is underway.

Keywords: antiparasitic activities, halogenative annulation, spirocycles, spirocyclization

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Authors: Rayhaneh Amooaghaie, Masoomeh Nabaei

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In this study, 200 µM Cd reduced relative seed germination, root elongation tolerance and seed germination tolerance index of Catharanthus roseus. The melatonin improved seed germination, germination velocity, seedling length and vigor index under Cd stress in a dose-dependent manner and the maximum biological responses obtained by 100 μM melatonin. However, 200-400 μM melatonin and 400 μM SNP had negative effects that evidenced as lower germination indices and poor establishment of seedlings. The cadmium suppressed amylase activity and contents of soluble and reducing sugars in germinating seeds, thereby reduced seed germination and subsequent seedling growth whereas increased electrolyte leakage. These Cd-induced inhibitory effects were ameliorated by melatonin.

Keywords: cadmium, Catharanthus roseus, melatonin, seed germination

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Authors: Anna Romanova, Morteza A. Alani

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Corrosion of concrete sewer pipes induced by sulfuric acid is an acknowledged problem and a ticking time-bomb to sewer operators. Whilst the chemical reaction of the corrosion process is well-understood, the indirect roles of other parameters in the corrosion process which are found in sewer environment are not highly reflected on. This paper reports on a field studies undertaken in Austria and United Kingdom, where the parameters of temperature, pH, H2S and CO2 were monitored over a period of time. The study establishes that (i) effluent temperature and pH have similar daily pattern and peak times, When examined in minutes scale, (ii) H2S and CO2 have an identical hourly pattern, (iii) H2S instant or shifted relation to effluent temperature is governed by the root mean square value of CO2.

Keywords: concrete corrosion, carbon dioxide, hydrogen sulphide, sewer pipe, sulfuric acid

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Authors: S. Ameddah, O. Deffa, H. Aissaoui, A. Menad, R. Mekkiou, F. Benayache, S. Benayache

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Acetylhydrazide (ACHD) is a metabolite of the anti-tubercular drug isoniazid (INH) that has been implicated in liver damage. This study was designed to evaluate hapatoprotective of n-BuOH extract of Heliotrpium undulatum (HUBE) in ACHD hepatotoxicity in rats. Hepatic damage was induced by administration of ACHD (300 mg/Kg op). The protection was affected by the administration of HUBE (200 mg/Kg op) for 14 days before ACHD administration, caused a decrease in LPO levels and in the transaminase and ALP levels and restored the GSH and its related enzymes (GPx, GST, GR) (50-62 %). Simultaneous administration of HUBE afforded a partial protection in statue of hepatic GSH conjugating enzymes upon administration of ACHD.

Keywords: heliotrpium undulatum, acetylhydrazide, glutathione conjugating enzymes, oxydatif stress, heaptoprotectif effect

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Authors: Yesim Tumsek, Erkan Celebi

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In order to simulate the infinite soil medium for soil-foundation interaction problem, the essential geotechnical parameter on which the foundation stiffness depends, is the value of soil shear modulus. This parameter directly affects the site and structural response of the considered model under earthquake ground motions. Strain-dependent shear modulus under cycling loads makes difficult to estimate the accurate value in computation of foundation stiffness for the successful dynamic soil-structure interaction analysis. The aim of this study is to discuss in detail how to use the appropriate value of soil shear modulus in the computational analyses and to evaluate the effect of the variation in shear modulus with strain on the impedance functions used in the sub-structure method for idealizing the soil-foundation interaction problem. Herein, the impedance functions compose of springs and dashpots to represent the frequency-dependent stiffness and damping characteristics at the soil-foundation interface. Earthquake-induced vibration energy is dissipated into soil by both radiation and hysteretic damping. Therefore, flexible-base system damping, as well as the variability in shear strengths, should be considered in the calculation of impedance functions for achievement a more realistic dynamic soil-foundation interaction model. In this study, it has been written a Matlab code for addressing these purposes. The case-study example chosen for the analysis is considered as a 4-story reinforced concrete building structure located in Istanbul consisting of shear walls and moment resisting frames with a total height of 12m from the basement level. The foundation system composes of two different sized strip footings on clayey soil with different plasticity (Herein, PI=13 and 16). In the first stage of this study, the shear modulus reduction factor was not considered in the MATLAB algorithm. The static stiffness, dynamic stiffness modifiers and embedment correction factors of two rigid rectangular foundations measuring 2m wide by 17m long below the moment frames and 7m wide by 17m long below the shear walls are obtained for translation and rocking vibrational modes. Afterwards, the dynamic impedance functions of those have been calculated for reduced shear modulus through the developed Matlab code. The embedment effect of the foundation is also considered in these analyses. It can easy to see from the analysis results that the strain induced in soil will depend on the extent of the earthquake demand. It is clearly observed that when the strain range increases, the dynamic stiffness of the foundation medium decreases dramatically. The overall response of the structure can be affected considerably because of the degradation in soil stiffness even for a moderate earthquake. Therefore, it is very important to arrive at the corrected dynamic shear modulus for earthquake analysis including soil-structure interaction.

Keywords: clay soil, impedance functions, soil-foundation interaction, sub-structure approach, reduced shear modulus

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Authors: Mohamed A. Deyab, Omnia El-Shamy

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The main objective of this case study is to integrate the advantages of cathodic protection technologies in order to lessen chloride-induced corrosion in reinforced concrete. This research employs potentiodynamic polarisation, impedance spectroscopy (EIS), and surface characteristics. The results showed how effectively the new cathodic control strategy is preventing corrosion of the concrete iron rods. Over time, the protective system becomes more reliable and effective. The potentials of the zinc electrode persist still more negative after 30 days, implying that the zinc electrode can maintain powerful electrocatalytic behavior for a long period of time. As per the electrochemical impedance spectroscopy (EIS), using the CP technique reduces the rate of corrosion of rebar iron in cementitious materials over time.

Keywords: cathodic protection, corrosion, reinforced concrete, chloride

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Authors: Hassina Harkat, Samiha Taybe, Salima Loucif, Valérie Beneteau, Patrick Pale

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Indole and its derivatives have attracted great interest because of their importance in the synthetic organic and medicinal chemistry. They are widely used as anti hypertension, anti tubercular, anticancer activity, antiviral, Alzheimer's disease, antioxidant properties, and free radical induced lipid peroxidation. Many drugs and natural products contain indole moiety, such as the vinca alkaloids, fungal metabolites and marine natural products. Generally applicable synthetic methods for indole moiety involve ring closure to form the pyrrole. Indole derivatives can also be accessed by further functionalization of the indole nucleus. Therefore we report a mild and efficient protocol for the synthesis of analogues of indole catalyzed via zeolithe USY doped with CuI under solvent-free conditions.

Keywords: indole, zeolithe, USY-CuI, heterogeneous catalysis

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Authors: Vijayakameswara Rao Neralla, Jueun Jeon, Jae Hyung Park

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To develop a potential nanocarrier for diagnosis and treatment of rheumatoid arthritis (RA), we prepared a hyaluronic acid (HA)-5β-cholanic acid (CA) conjugate with an acid-labile ketal linker. This conjugate could self-assemble in aqueous conditions to produce pH-responsive HA-CA nanoparticles as potential carriers of the anti-inflammatory drug methotrexate (MTX). MTX was rapidly released from nanoparticles under inflamed synovial tissue in RA. In vitro cytotoxicity data showed that pH-responsive HA-CA nanoparticles were non-toxic to RAW 264.7 cells. In vivo biodistribution results confirmed that, after their systemic administration, pH-responsive HA-CA nanoparticles selectively accumulated in the inflamed joints of collagen-induced arthritis mice. These results indicate that pH-responsive HA-CA nanoparticles represent a promising candidate as a drug carrier for RA therapy.

Keywords: rheumatoid arthritis, hyaluronic acid, nanocarrier, self-assembly, MTX

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Authors: Zelikha Labbani

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The In Vitro isolated micro spore culture is the most powerful androgenic pathway to produce doubled haploid plants in the short time. To deviate a micro spore toward embryogenesis, a number of factors, different for each species, must concur at the same time and place. Once induced, the micro spore undergoes numerous changes at different levels, from overall morphology to gene expression. Induction of micro spore embryogenesis not only implies the expression of an embryogenic program, but also a stress-related cellular response and a repression of the gametophytic program to revert the microspore to a totipotent status. As haploid single cells, micro spore became a strategy to achieve various objectives particularly in genetic engineering. In this study we would show the most recent advances in the producing haploid embryos via In Vitro isolated micro spore culture.

Keywords: haploid cells, In Vitro isolated microspore culture, success

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Authors: Andrey A. Lipovskii, Alexey V. Redkov, Vyacheslav V. Rusan, Dmitry K. Tagantsev, Valentina V. Zhurikhina

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The presented research is related to the development of recently proposed technique of the formation of composite materials, like optical glass-ceramics, with predetermined structure and properties of the crystalline component. The technique is based on the control of the size and concentration of the crystalline grains using the phenomenon of glass-ceramics decrystallization (vitrification) induced by ion-exchange. This phenomenon was discovered and explained in the beginning of the 2000s, while related theoretical description was given in 2016 only. In general, the developed theory enables one to model the process and optimize the conditions of ion-exchange processing of glass-ceramics, which provide given properties of crystalline component, in particular, profile of the average size of the crystalline grains. The optimization is possible if one knows two dimensionless parameters of the theoretical model. One of them (β) is the value which is directly related to the solubility of crystalline component of the glass-ceramics in the glass matrix, and another (γ) is equal to the ratio of characteristic times of ion-exchange diffusion and crystalline grain dissolution. The presented study is dedicated to the development of experimental technique and simulation which allow determining these parameters. It is shown that these parameters can be deduced from the data on the space distributions of diffusant concentrations and average size of crystalline grains in the glass-ceramics samples subjected to ion-exchange treatment. Measurements at least at two temperatures and two processing times at each temperature are necessary. The composite material used was a silica-based glass-ceramics with crystalline grains of Li2OSiO2. Cubical samples of the glass-ceramics (6x6x6 mm3) underwent the ion exchange process in NaNO3 salt melt at 520 oC (for 16 and 48 h), 540 oC (for 8 and 24 h), 560 oC (for 4 and 12 h), and 580 oC (for 2 and 8 h). The ion exchange processing resulted in the glass-ceramics vitrification in the subsurface layers where ion-exchange diffusion took place. Slabs about 1 mm thick were cut from the central part of the samples and their big facets were polished. These slabs were used to find profiles of diffusant concentrations and average size of the crystalline grains. The concentration profiles were determined from refractive index profiles measured with Max-Zender interferometer, and profiles of the average size of the crystalline grains were determined with micro-Raman spectroscopy. Numerical simulation were based on the developed theoretical model of the glass-ceramics decrystallization induced by ion exchange. The simulation of the processes was carried out for different values of β and γ parameters under all above-mentioned ion exchange conditions. As a result, the temperature dependences of the parameters, which provided a reliable coincidence of the simulation and experimental data, were found. This ensured the adequate modeling of the process of the glass-ceramics decrystallization in 520-580 oC temperature interval. Developed approach provides a powerful tool for fine tuning of the glass-ceramics structure, namely, concentration and average size of crystalline grains.

Keywords: diffusion, glass-ceramics, ion exchange, vitrification

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Authors: Khater Nadia, Garah Kenza

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Moringa stenopetala is a rapidly growing, unappreciated tree regarded as the "miracle tree" for its food, feed, and medicinal benefits. It appears to be a versatile and promising species for use under changing conditions. To evaluate the effect of water stress on germination seeds of M. stenopetala, three different concentrations PEG- 6000 (4, 8, and 12 per cent) along with a control in a factorial experiment based on a completely randomized design with five replications. The results revealed that water potential significantly reduced germination rate (82.5%) and average germination time. Germination speed in T3 by 93%, kinetics germination in T2 (39), germination index in T2 (102) and germination vigor index in T2 (91.25) were increased in the osmotic potential of PEG solution. By following these steps, we can improve the chances of successful germination of M. stenopetala seeds under water stress conditions

Keywords: moringa stenopetala, PEG, water stress, rate

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Authors: Sarah Crawford, Gerry Lesley

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This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

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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 1^st and 2^nd 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 1^st 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 1^st and 2^nd week showed totally reduction i.e. 103.4% [P=0.0001]. Group B showed 24.7% change from baseline to 1^st week and 53.6% for 2^nd 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 1^st week and 33.3% in 2^nd week. The p value with Wilcoxon was significant with 0.0025 in Group A for 1^st week follow up and 0.000 for 2^nd 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

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Authors: I. Cerrillo, A. Carrillo-Vico, M. A. Ortega, B. Escudero-López, N. Álvarez-Sánchez, F. Martín, M. S. Fernández-Pachón

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Melatonin is a bioactive compound involved in multiple biological activities such as glucose tolerance, circadian rhythm regulation, antioxidant defense or immune system action. In elderly subjects the intake of foods and drinks rich in melatonin is very important due to its endogenous level decreases with age. Alcoholic fermentation is a process carried out in fruits, vegetables and legumes to obtain new products with improved bioactive compounds profile in relation to original substrates. Alcoholic fermentation process carried out by Saccharomycetaceae var. Pichia kluyveri induces an important synthesis of melatonin in orange juice. A novel beverage derived of fermented orange juice could be a promising source of this bioactive compound. The aim of the present study was to determine whether the acute intake of fermented orange juice increase the levels of urinary 6-sulfatoxymelatonin in healthy humans. Nine healthy volunteers (7 women and 2 men), aged between 20 and 25 years old and BMI of 21.1  2.4 kg/m2, were recruited. On the study day, participants ingested 500 mL of fermented orange juice. The first urine collection was made before fermented orange juice consumption (basal). The rest of urine collections were made in the following time intervals after fermented orange juice consumption: 0-2, 2-5, 5-10, 10- 15 and 15-24 hours. During the experimental period only the consumption of water was allowed. At lunch time a meal was provided (60 g of white bread, two slices of ham, a slice of cheese, 125 g of sweetened natural yoghurt and water). The subjects repeated the protocol with orange juice following a 2-wk washout period between both types of beverages. The levels of 6-sulfatoxymelatonin (6-SMT) were measured in urine recollected at different time points using the Melatonin-Sulfate Urine ELISA (IBL International GMBH, Hamburg, Germany). Levels of 6-SMT were corrected to those of creatinine for each sample. A significant (p < 0.05) increase in urinary 6-SMT levels was observed between 2-5 hours after fermented orange juice ingestion with respect to basal values (increase of 67,8 %). The consumption of orange juice did not induce any significant change in urinary 6-SMT levels. In addition, urinary 6-SMT levels obtained between 2-5 hours after fermented orange juice ingestion (115,6 ng/mg) were significantly different (p < 0.05) from those of orange juice (42,4 ng/mg). The enhancement of urinary 6-SMT after the ingestion of 500 mL of fermented orange juice in healthy humans compared to orange juice could be an important advantage of this novel product as an excellent source of melatonin. Fermented orange juice could be a new functional food, and its consumption could exert a potentially positive effect on health in both the maintenance of health status and the prevention of chronic diseases.

Keywords: fermented orange juice, functional beverage, healthy human, melatonin

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