Search results for: carragenan induced edema
2266 Toxicity of Cymbopogon proximus (Maharaib) Oil Extract to Newzealand Rabbits
Authors: A. B. Amna, M. A. E. Samia, A. K. Hassan
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The clinical, pathological, hematological and biological changes in Newzealand rabbits groups given daily oral doses of 0.1,0.25 and 0.5 ml/kg body weight/day of Cpmbopogon proximus oil extract were investigated in an experiment durated for 21 days. Other than the dose co-related mortality rates, the clinical signs were observed daily after dosing to be low appetite and nervous signs including restlessness and increased consciousness. Pulmonary excretion of the oil extract led to bloody spots on the lungs, lymphocyte infiltration, congestion and edema. Renal glumeruli manifested lymphocyte infiltration in addition to shrinkages and easinophilic material in the medulla, if considered with the corticomedullary generalized necrosis and the significant changes in urea, they can explain the renal dysfunction. Hepatic malfunction was manifested by significant changes in serum alkaline phosphatase and aspartate transferases accompanied by the congested, fatty changed livers. The direct physical effect of the extracted oil was detected by the catarrhal inflammation of the intestines.There was no significant haematological change except for the slight changes in RBCs and MCVs in rabbits given the highest dose. Future work for Cpmbopogon proximus oil extract was forwarded and practical implications of the result were highlighted.Keywords: toxicity, cymbopogon proximus (maharaib), oil extract, Newzealand rabbits
Procedia PDF Downloads 4832265 Effect of Povidone Iodine in Treatment of Epidemic Keratoconjunctivitis: Clinical Trail Study
Authors: Mohammad Hossain Validad
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Background and Aim: Epidemic keratoconjunctivitis is a type of conjunctivitis caused by adenoviruses that can spread rapidly through direct and indirect contact. The aim of this study was to evaluate the therapeutic effects of Povidone-Iodine 0.4% and 0.2% in improving the symptoms and signs of patients with epidemic keratoconjunctivitis. Materials and Methods: In this clinical trial study, 60 patients with a mean age of 27.8±8.4 years who were eligible for inclusion criteria were randomly divided into three groups. The first group received eye drops of Povidone-Iodine 0.4% and betamethasone 0.1%, the second group received PovidoneIodine 0.2% and betamethasone 0.1% and the third group received betamethasone 0.1%. Follow-ups were on the first, fourth, seventh and tenth days after starting treatment. Parameters examined at each examination were hyperaemia, mucopurulent discharge, eyelid edema, hemorrhage, and subepithelial infiltration. Results: The results showed that mucopurulent discharge on the fourth day of the examination (P = 0.005) and the seventh day of the examination (P = 0.001) were significantly different in the three treatment groups. Sub-epithelial infiltration on the tenth day after treatment did not show a significant difference in the 3 groups (P = 0.287). Conclusion: Based on the results of this study, Povidone-Iodine is more effective in relieving some of signs of EKC, such as reduced mucopurulent discharge than steroids alone.Keywords: EKC, topical bethadine, adenovirus, sub epithelial opacity
Procedia PDF Downloads 762264 Albumin-Induced Turn-on Fluorescence in Molecular Engineered Fluorescent Probe for Biomedical Application
Authors: Raja Chinnappan, Huda Alanazi, Shanmugam Easwaramoorthi, Tanveer Mir, Balamurugan Kanagasabai, Ahmed Yaqinuddin, Sandhanasamy Devanesan, Mohamad S. AlSalhi
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Serum albumin (SA) is a highly rich water-soluble protein in plasma. It is known to maintain the living organisms' health and help to maintain the proper liver function, kidney function, and plasma osmolality in the body. Low levels of serum albumin are an indication of liver failure and chronic hepatitis. Therefore, it is important to have a low-cost, accurate and rapid method. In this study, we designed a fluorescent probe, triphenylamine rhodanine-3-acetic acid (mRA), which triggers the fluorescence signal upon binding with serum albumin (SA). mRA is a bifunctional molecule with twisted intramolecular charge transfer (TICT)-induced emission characteristics. An aqueous solution of mRA has an insignificant fluorescence signal; however, when mRA binds to SA, it undergoes TICT and turns on the fluorescence emission. A SA dose-dependent fluorescence signal was performed, and the limit of detection was found to be less than ng/mL. The specific binding of SA was tested from the cross-reactivity study using similar structural or functional proteins.Keywords: serum albumin, fluorescent sensing probe, liver diseases, twisted intramolecular charge transfer
Procedia PDF Downloads 172263 Study the Effect of Leading-Edge Serration at Owl Wing Feathers on Flow-Induced Noise Generation
Authors: Suprabha Islam, Sifat Ullah Tanzil
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During past few decades, being amazed by the excellent silent flight of owl, scientists have been trying to demystify the unique features of its wing feathers. Our present study is dedicated to taking our understanding further on this phenomenon. In this present study, a numerical investigation was performed to analyze how the shape of the leading-edge serration at owl wing feathers effects the flow-induced noise generation. For the analysis, an owl inspired single feather wing model was prepared for both with and without serrations at the leading edge. The serration profiles were taken at different positions of the vane length for a single feather. The broadband noise was studied to quantify the local contribution to the total acoustic power generated by the flow, where the results clearly showed the effect of serrations in reducing the noise generation. It was also clearly visible that the shape of the serration has a very strong influence on noise generation. The frequency spectrum of noise was also analyzed and a strong relation was found between the shape of the serration and the noise generation. It showed that the noise suppression is strongly influenced by the height to length ratio of the serration. With the increase in height to length ratio, the noise suppression is enhanced further.Keywords: aeroacoustics, aerodynamic, biomimetics, serrations
Procedia PDF Downloads 1682262 Principal Component Analysis Combined Machine Learning Techniques on Pharmaceutical Samples by Laser Induced Breakdown Spectroscopy
Authors: Kemal Efe Eseller, Göktuğ Yazici
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Laser-induced breakdown spectroscopy (LIBS) is a rapid optical atomic emission spectroscopy which is used for material identification and analysis with the advantages of in-situ analysis, elimination of intensive sample preparation, and micro-destructive properties for the material to be tested. LIBS delivers short pulses of laser beams onto the material in order to create plasma by excitation of the material to a certain threshold. The plasma characteristics, which consist of wavelength value and intensity amplitude, depends on the material and the experiment’s environment. In the present work, medicine samples’ spectrum profiles were obtained via LIBS. Medicine samples’ datasets include two different concentrations for both paracetamol based medicines, namely Aferin and Parafon. The spectrum data of the samples were preprocessed via filling outliers based on quartiles, smoothing spectra to eliminate noise and normalizing both wavelength and intensity axis. Statistical information was obtained and principal component analysis (PCA) was incorporated to both the preprocessed and raw datasets. The machine learning models were set based on two different train-test splits, which were 70% training – 30% test and 80% training – 20% test. Cross-validation was preferred to protect the models against overfitting; thus the sample amount is small. The machine learning results of preprocessed and raw datasets were subjected to comparison for both splits. This is the first time that all supervised machine learning classification algorithms; consisting of Decision Trees, Discriminant, naïve Bayes, Support Vector Machines (SVM), k-NN(k-Nearest Neighbor) Ensemble Learning and Neural Network algorithms; were incorporated to LIBS data of paracetamol based pharmaceutical samples, and their different concentrations on preprocessed and raw dataset in order to observe the effect of preprocessing.Keywords: machine learning, laser-induced breakdown spectroscopy, medicines, principal component analysis, preprocessing
Procedia PDF Downloads 872261 Methylglyoxal Induced Glycoxidation of Human Low Density Lipoprotein: A Biophysical Perspective and Its Role in Diabetes and Periodontitis
Authors: Minhal Abidi, Moinuddin
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Diabetes mellitus (DM) induced metabolic abnormalities causes oxidative stress which leads to the pathogenesis of complications associated with diabetes like retinopathy, nephropathy periodontitis etc. Combination of glycation and oxidation 'glycoxidation' occurs when oxidative reactions affect the early state of glycation products. Low density lipoprotein (LDL) is prone to glycoxidative attack by sugars and methylglyoxal (MGO) being a strong glycating agent may have severe impact on its structure and consequent role in diabetes. Pro-inflammatory cytokines like IL1β and TNFα produced by the action of gram negative bacteria in periodontits (PD) can in turn lead to insulin resistance. This work discusses modifications to LDL as a result of glycoxidation. The changes in the protein molecule have been characterized by various physicochemical techniques and the immunogenicity of the modified molecules was also evaluated as they presented neo-epitopes. Binding of antibodies present in diabetes patients to the native and glycated LDL has been evaluated. Role of modified epitopes in the generation of antibodies in diabetes and periodontitis has been discussed. The structural perturbations induced in LDL were analyzed by UV–Vis, fluorescence, circular dichroism and FTIR spectroscopy, molecular docking studies, thermal denaturation studies, Thioflavin T assay, isothermal titration calorimetry, comet assay. MALDI-TOF, ketoamine moieties, carbonyl content and HMF content were also quantitated in native and glycated LDL. IL1β and TNFα levels were also measured in the type 2 DM and PD patients. We report increased carbonyl content, ketoamine moieties and HMF content in glycated LDL as compared to native analogue. The results substantiate that in hyperglycemic state MGO modification of LDL causes structural perturbations making the protein antigenic which could obstruct normal physiological functions and might contribute in the development of secondary complications in diabetic patients like periodontitis.Keywords: advanced glycation end products, diabetes mellitus, glycation, glycoxidation, low density lipoprotein, periodontitis
Procedia PDF Downloads 1912260 Evaluation of Antidiabetic Activity of a Combination Extract of Nigella Sativa & Cinnamomum Cassia in Streptozotocin Induced Type-I Diabetic Rats
Authors: Ginpreet Kaur, Mohammad Yasir Usmani, Mohammed Kamil Khan
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Diabetes mellitus is a disease with a high global burden and results in significant morbidity and mortality. In India, the number of people suffering with diabetes is expected to rise from 19 to 57 million in 2025. At present, interest in herbal remedies is growing to reduce the side effects associated with conventional dosage form like oral hypoglycemic agents and insulin for the treatment of diabetes mellitus. Our aim was to investigate the antidiabetic activities of combinatorial extract of N. sativa & C. cassia in Streptozotocin induced type-I Diabetic Rats. Thus, the present study was undertaken to screen postprandial glucose excursion potential through α- glucosidase inhibitory activity (In Vitro) and effect of combinatorial extract of N. sativa & C. cassia in Streptozotocin induced type-I Diabetic Rats (In Vivo). In addition changes in body weight, plasma glucose, lipid profile and kidney profile were also determined. The IC50 values for both extract and Acarbose was calculated by extrapolation method. Combinatorial extract of N. sativa & C. cassia at different dosages (100 and 200 mg/kg orally) and Metformin (50 mg/kg orally) as the standard drug was administered for 28 days and then biochemical estimation, body weights and OGTT (Oral glucose tolerance test) were determined. Histopathological studies were also performed on kidney and pancreatic tissue. In In-Vitro the combinatorial extract shows much more inhibiting effect than the individual extracts. The results reveals that combinatorial extract of N. sativa & C. cassia has shown significant decrease in plasma glucose (p<0.0001), total cholesterol and LDL levels when compared with the STZ group The decreasing level of BUN and creatinine revealed the protection of N. sativa & C. cassia extracts against nephropathy associated with diabetes. Combination of N. sativa & C. cassia significantly improved glucose tolerance to exogenously administered glucose (2 g/kg) after 60, 90 and 120 min interval on OGTT in high dose streptozotocin induced diabetic rats compared with the untreated control group. Histopathological studies shown that treatment with N. sativa & C. cassia extract alone and in combination restored pancreatic tissue integrity and was able to regenerate the STZ damaged pancreatic β cells. Thus, the present study reveals that combination of N. sativa & C. cassia extract has significant α- glucosidase inhibitory activity and thus has great potential as a new source for diabetes treatment.Keywords: lipid levels, OGTT, diabetes, herbs, glucosidase
Procedia PDF Downloads 4302259 Protective Effect of Essential Oil from Chamaecyparis obtusa on Anxiety-Related Behaviors and Cytokine Abnormalities Induced by Early Life Stress
Authors: Hae Jeong Park, Joo-Ho Chung
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In this study, the effect of essential oil from Chamaecyparis obtuse (EOCO) on early life stress using maternal separation (MS) rats was investigated. Anxiety-related behaviors were examined in MS rats using the elevated plus-maze (EPM) test. The changes of gene expressions by EOCO in the hippocampus of MS rats were analyzed using a microarray method. Rats in the MS groups were separated from their respective mothers from postnatal day (pnd) 14 to 28. Rats in the EOCO-treated groups were exposed to EOCO for 1 h or 2 h by inhalation from pnd 21 to 28. The EOCO-treated MS rats showed decreased anxiety-related behaviors compared to the MS rats in the EPM test. In the microarray analysis, EOCO downregulated the expressions of cytokine genes such as Ccl2, Il6, Cxcl10, Ccl19, and Il1rl in the hippocampus of MS rats, and it was also confirmed through RT-PCR. In particular, the expressions of Ccl2 and Il6 were predominantly decreased by EOCO in the hippocampus of MS rats. Interestingly, their protein expressions were also reduced by EOCO in MS rats. These results indicate that EOCO decreases MS-induced anxiety-related behaviors, and modulate cytokines, particularly Ccl2 and Il6, in the hippocampus of MS rats.Keywords: anxiety-related behavior, Chamaecyparis obtuse, cytokine gene, early-life stress, maternal separation
Procedia PDF Downloads 3892258 Antioxidant Effects of Withania Somnifera (Ashwagandha) on Brain
Authors: Manju Lata Sharma
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Damage to cells caused by free radicals is believed to play a central role in the ageing process and in disease progression. Withania somnifera is widely used in ayurvedic medicine, and it is one of the ingredients in many formulations to increase energy, improve overall health and longevity and prevent disease. Withania somnifera possesses antioxidative properties. The antioxdant activity of Withania somnifera consisting of an equimolar concentration of active principles of sitoindoside VII-X and withaferin A. The antioxidant effect of Withania somnifera extract was investigated on lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) activity in mice. Aim: To study the antioxidant activity of an extract of Withania somnifera leaf against a mice model of chronic stress. Healthy swiss albino mice (3-4 months old) selected from an inbred colony were divided in to 6 groups. Biochemical estimation revealed that stress induced a significant change in SOD, LPO, CAT AND GPX. These stress induced perturbations were attenuated Withania somnifera (50 and 100 mg/kg BW). Result: Withania somnifera tended to normalize the augmented SOD and LPO activities and enhanced the activities of CAT and GPX. The result indicates that treatment with an alcoholic extract of Withania somnifera produced a significant decrease in LPO ,and an increase in both SOD and CAT in brain mice. This indicates that Withania somnifera extract possesses free radical scavenging activity .Keywords: Withania somnifera, antioxidant, lipid peroxidation, brain
Procedia PDF Downloads 3662257 Evaluation of Chemoprotective Effect of NBRIQU16 against N-Methyl-N-Nitro-N-Nitrosoguanidine and NaCl-Induced Gastric Carcinomas in Wistar Rats
Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, C. V. Rao
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To investigate the chemoprotective potential of NBRIQU16 chemotype isolated from Argyreia speciosa (Family: Convolvulaceae) on N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and NaCl-induced gastric carcinomas in Wistar rats. Forty-six male 6-week-old Wistar rats were divided into two groups. Thirty rats in group A were fed with a diet supplemented with 8 % NaCl for 20 weeks and simultaneously given N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) in drinking water at a concentration of 100 ug/ml for the first 17 weeks. After administration of the carcinogen, 200 and 400 mg/kg of NBRIQU16 were administered orally once a day throughout the study. From week 18, these rats were given normal water. From week 21, these rats were fed with a normal diet for 15 weeks. Group B containing 16 rats was fed standard diet for thirty-five days. It served as control. Ten rats from group A were sacrificed after 20 weeks. Scarification of remaining animals was conducted after 35 weeks. Entire stomach and some part of the duodenum were incised parallel to the greater curvature, and the samples were collected. After opening the stomach location and size of tumors were recorded. The number of tumors with their locations and sizes were recorded. Expression of survivin was examined by recording the Immunohistochemistry of the specimens. The treatment with NBRIQU16 significantly reduced the nodule incidence and nodule multiplicity in the rats after MNNG administration. Surviving expression in glandular stomachs of normal rats, of rats in middle induction period, in adenocarcinomas and NBRIQU16 treated tissues adjacent to tumor were 0, 42.0 %, 79.3%, and 36.4 %, respectively. Expression of survivin was significantly different as compared to the normal rats. Histological observations of stomach tissues too correlated with the biochemical observations.These finding powerfully supports that NBRIQU16 chemopreventive effect by suppressing the tumor burden and restoring the activities of gastric cancer marker enzymes on MNNG and NaCl-induced gastric carcinomas in Wistar rats.Keywords: Argyreia speciosa, gastric carcinoma, immunochemistry, NBRIQU16
Procedia PDF Downloads 2982256 Mixing Behaviors of Shear-Thinning Fluids in Serpentine-Channel Micromixers
Authors: Rei-Tang Tsai, Chih-Yang Wu, Chia-Yuan Chang, Ming-Ying Kuo
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This study aims to investigate the mixing behaviors of deionized (DI) water and carboxymethyl cellulose (CMC) solutions in C-shaped serpentine micromixers over a wide range of flow conditions. The flow of CMC solutions exhibits shear-thinning behaviors. Numerical simulations are performed to investigate the effects of the mean flow speed, fluid properties and geometry parameters on flow and mixing in the micromixers with serpentine channel of the same overall channel length. From the results, we can find the following trends. When fluid mixing is dominated by convection, the curvature-induced vortices enhance fluid mixing effectively. The mixing efficiency of a micromixer consisting of semicircular C-shaped repeating units with a smaller center-line radius is better than that of a micromixer consisting of major-segment repeating units with a larger center-line radius. The viscosity of DI water is less than the overall average apparent viscosity of CMC solutions, and so the effect of curvature-induced vortices on fluid mixing in DI water is larger than that in CMC solutions for the cases with the same mean flow speed.Keywords: curved channel, microfluidics, mixing, non-newtonian fluids, vortex
Procedia PDF Downloads 4412255 Effective Wind-Induced Natural Ventilation in a Residential Apartment Typology
Authors: Tanvi P. Medshinge, Prasad Vaidya, Monisha E. Royan
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In India, cooling loads in residential sector is a major contributor to its total energy consumption. Due to the increasing cooling need, the market penetration of air-conditioners is further expected to rise. Natural Ventilation (NV), however, possesses great potential to save significant energy consumption especially for residential buildings in moderate climates. As multifamily residential apartment buildings are designed by repetitive use of prototype designs, deriving individual NV based design prototype solutions for a combination of different wind incidence angles and orientations would provide significant opportunity to address the rise in cooling loads by residential sector. This paper presents the results of NV performance of a selected prototype apartment design with a cluster of four units in Pune, India, and an attempt to improve the NV performance through design modifications. The water table apparatus, a physical modelling tool, is used to study the flow patterns and simulate wind-induced NV performance. Quantification of NV performance is done by post processing images captured from video recordings in terms of percentage of area with good and poor access to ventilation. NV performance of the existing design for eight wind incidence angles showed that of the cluster of four units, the windward units showed good access to ventilation for all rooms, and the leeward units had lower access to ventilation with the bedrooms in the leeward units having the least access. The results showed improved performance in all the units for all wind incidence angles to more than 80% good access to ventilation. Some units showed an additional improvement to more than 90% good access to ventilation. This process of design and performance evaluation improved some individual units from 0% to 100% for good access to ventilation. The results demonstrate the ease of use and the power of the water table apparatus for performance-based design to simulate wind induced NV.Keywords: fluid dynamics, prototype design, natural ventilation, simulations, water table apparatus, wind incidence angles
Procedia PDF Downloads 2292254 Role of Oxidative Stress and Nitric Oxide in the Protective Effects of Simvastatine against Isoniazid-Rifampicin-Induced Hepatotoxicity in Rats
Authors: Mabroka Omar Sherehe
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Despite the great efficacy of isoniazid (INH) and rifampicine (RIF) combination in the treatment of tuberculosis, hepatotoxicity is the most common serious complication. The potential protective effect of simvastatin (sim) against combination-induced hepatotoxicity was investigated in the present study. The administration of INH-RIF combination (50mg/kg each for 14 days) resulted in a significant increased activities of serum alanine and aspartate aminotransferases, such effects were further supported by histopathological studies. INH-RIF combination produced a significant increase in liver lipid, decreased SOD and CAT, and a significant depletion of GSH level. Additionally, treatment with INH-RIF combination resulted in a significant increase in liver MPO activity. The lipid-lowering drug, Sim demonstrated in the current study an evident antioxidant action, such effect was mediated via decreasing the elevated MDA, MPO, and restoring liver CAT activity. Additionally, Sim restored liver NO level to near basal value Furthermore, one cannot rule out the lipid-lowering effect of Sim that would probably add to its beneficial hepatoprotective antioxidant activity, where Sim decreased the elevated cholesterol, TGs and LDL cholesterol level and increased the serum HDL cholesterol level.Keywords: isoniazid, rifampicine, oxidative stress, nitric oxide
Procedia PDF Downloads 6162253 Induced Thermo-Osmotic Convection for Heat and Mass Transfer
Authors: Francisco J. Arias
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Consideration is given to a mechanism of heat and mass transport in solutions similar than that of natural convection but with one important difference. Here the mechanism is not promoted by density differences in the fluid occurring due to temperature gradients (coefficient of thermal expansion) but rather by solubility differences due to the thermal dependence of the solubility (coefficient of thermal solubility). Utilizing a simplified physical model, it is shown that by the proper choice of the concentration of a given solution, convection might be induced by the alternating precipitation of the solute -when the solution becomes supersaturated, and its posterior recombination when changes in temperature occurs. The spontaneous change in the Gibbs free energy during the mixing is the driven force for the mechanism. The maximum extractable energy from this new type of thermal convection was derived. Experimental data from a closed-loop circuit was obtained demonstrating the feasibility for continuous separation and recombination of the solution. This type of heat and mass transport -which doesn’t depend on gravity, might potentially be interesting for heat and mass transport downwards (as in solar-roof collectors to inside homes), horizontal (e.g., microelectronic applications), and in microgravity (space technology). Also, because the coefficient of thermal solubility could be positive or negative, the investigated thermo-osmosis convection can be used either for heating or cooling.Keywords: natural convection, thermal gradient, solubility, osmotic pressure
Procedia PDF Downloads 2932252 Preventive Effect of Stem Back Extracts of Coula edulis Baill. against High-Fat / High Sucrose Diet-Induced Insulin Resistance and Oxidative Stress in Rats
Authors: Eric Beyegue, Boris Azantza, Judith Laure Ngondi, Julius E. Oben
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Background: Insulin resistance (IR) and oxidative stress are associated with obesity, diabetes mellitus, and other cardio metabolic disorders. The aim of this study was to investigate the effect of Coula edulis extracts (CEE) on insulin resistance and oxidative stress markers in high-fat/high sucrose diet-induced insulin resistance in rats. Materials and Methods: Thirty male rats were divided into 6 groups of 5 rats each fed, received daily oral administration of CE extracts for 8 weeks as follows: Group 1 or negative control group, fed with standard diet (SD); Group 2 fed with high-fat/high sucrose diet (HFHS) only; Group3 fed with HFHS + CEAq 200; Group 4 fed with HFHS + CEAq 400; Group 5 fed with HFHS + CEEt 200; Group 6 fed with HFHS + CEEt 400. At the end of the experiment (8 weeks), animals were sacrificed plasma lipid profile, glucose, insulin, oxidative marker and digestive enzyme activities were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) was determined. Results: Feedings with HFHS significantly (p < 0.01) induced plasma hyperglycaemia, hyperinsulinaemia, increased triglyceride, total cholesterol, and low-density lipoprotein levels, decreased high-density lipoprotein levels, alterations of α amylase, and glucose-6-phosphatase activities, and oxidative stress. Daily oral administration with CEE for eight weeks after insulin resistance induction had a hypolipidaemic action, antioxidative activities and modulated metabolic markers. Ethanolic extract at the higher dose had the best effect on body weight gain and insulin resistance, whereas aqueous extract showed the better activity on hyperlipidemia. Conclusion: These results suggest that CEAq and CEEt at 400mg/kg are promising complementary supplements that can be used to protect better from metabolic disorders associated with HFHS.Keywords: Coula edulis Baill, high-fat / high sucrose diet, insulin resistance, oxidative stress
Procedia PDF Downloads 3052251 An Investigation of Anticancer Fluorinated Aza-Heterocycles
Authors: Darya O. Prima, Elena V. Vorontsova, Yuri G. Slizhov, Andrey V. Zibarev
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A broad family of carbocycle-fluorinated aza-heterocycles including 1,3-benzodiazoles (benzimidazoles), 1,2,3-benzotriazoles, 2,1,3-benzothia/selenadiazoles and 1,4-benzodiazines (quinoxalines) was synthesized in the unified way and assessed for cytotoxicity towards the Hep2 (laryngeal epidermoid carcinoma, a kind of oral cancer) cells. The diazoles, triazoles and selenadiazoles revealed low medium inhibitory concentrations IC50 = 2.2-26.4 µМ and induced the cells’ apoptosis at low concentrations C = 1-25 µМ. For selenadiazoles, cell death dynamics was observed already in the first hours after the treatment. Replacement of one atom F by group Me2N in some cases enlarged apoptotic activity of the compounds towards the Hep2 cells. In contrast, the archetypal (i.e. non-fluorinated) 1,3-benzodiazole, 1,2,3-benzotriazole and 2,1,3-benzoselenadiazole were low toxic (IC50 > 100 µM) and induced apoptosis only at high concentrations. The chlorinated congeners of the heterocycles under discussion were highly toxic towards the Hep2 cells but revealed insignificant ability to induce their apoptosis. Overall, the findings above suggest that fluorinated 1,3-benzodiazole, 1,2,3-benzotriazole and 2,1,3-benzoselenadiazole derivatives can be considered as potential anticancer drugs. For the laryngeal epidermoid carcinoma (for which, according to available statistics, the five-year survival rate remained ~50% during the past 30 years), it is especially important since surgical treatment is seriously complicated here thus encouraging medicament one.Keywords: Apoptosis, aza-heterocycles, cytotoxicity, fluorinated, Hep2 cells, synthesis
Procedia PDF Downloads 3392250 In vitro and in vivo Assessment of Cholinesterase Inhibitory Activity of the Bark Extracts of Pterocarpus santalinus L. for the Treatment of Alzheimer’s Disease
Authors: K. Biswas, U. H. Armin, S. M. J. Prodhan, J. A. Prithul, S. Sarker, F. Afrin
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Alzheimer’s disease (AD) (a progressive neurodegenerative disorder) is mostly predominant cause of dementia in the elderly. Prolonging the function of acetylcholine by inhibiting both acetylcholinesterase and butyrylcholinesterase is most effective treatment therapy of AD. Traditionally Pterocarpus santalinus L. is widely known for its medicinal use. In this study, in vitro acetylcholinesterase inhibitory activity was investigated and methanolic extract of the plant showed significant activity. To confirm this activity (in vivo), learning and memory enhancing effects were tested in mice. For the test, memory impairment was induced by scopolamine (cholinergic muscarinic receptor antagonist). Anti-amnesic effect of the extract was investigated by the passive avoidance task in mice. The study also includes brain acetylcholinesterase activity. Results proved that scopolamine induced cognitive dysfunction was significantly decreased by administration of the extract solution, in the passive avoidance task and inhibited brain acetylcholinesterase activity. These results suggest that bark extract of Pterocarpus santalinus can be better option for further studies on AD via their acetylcholinesterase inhibitory actions.Keywords: Pterocarpus santalinus, cholinesterase inhibitor, passive avoidance, Alzheimer’s disease
Procedia PDF Downloads 2492249 Application of Microbially Induced Calcite Precipitation Technology in Construction Materials: A Comprehensive Review of Waste Stream Contributions
Authors: Amir Sina Fouladi, Arul Arulrajah, Jian Chu, Suksun Horpibulsuk
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Waste generation is a growing concern in many countries across the world, particularly in urban areas with high rates of population growth and industrialization. The increasing amount of waste generated from human activities has led to environmental, economic, and health issues. Improper disposal of waste can result in air and water pollution, land degradation, and the spread of diseases. Waste generation also consumes large amounts of natural resources and energy, leading to the depletion of valuable resources and contributing to greenhouse gas emissions. To address these concerns, there is a need for sustainable waste management practices that reduce waste generation and promote resource recovery and recycling. Amongst these, developing innovative technologies such as Microbially Induced Calcite Precipitation (MICP) in construction materials is an effective approach to transforming waste into valuable and sustainable applications. MICP is an environmentally friendly microbial-chemical technology that applies microorganisms and chemical reagents to biological processes to produce carbonate mineral. This substance can be an energy-efficient, cost-effective, sustainable solution to environmental and engineering challenges. Recent research has shown that waste streams can replace several MICP-chemical components in the cultivation media of microorganisms and cementation reagents (calcium sources and urea). In addition to its effectiveness in treating hazardous waste streams, MICP has been found to be cost-effective and sustainable solution applicable to various waste media. This comprehensive review paper aims to provide a thorough understanding of the environmental advantages and engineering applications of MICP technology, with a focus on the contribution of waste streams. It also provides researchers with guidance on how to identify and overcome the challenges that may arise applying the MICP technology using waste streams.Keywords: waste stream, microbially induced calcite precipitation, construction materials, sustainability
Procedia PDF Downloads 792248 Cryptosporidium Parvum oocytic Antigen Induced a Pro-Inflammatory DC Phenotype
Authors: Connick K, Lalor R, Murphy A, O’Neill S. M., Rabab S. Zalat, Eman E. El Shanawany
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Cryptosporidium parvum is an opportunistic intracellular parasite that causes mild to severe diarrhea in human and animal populations and is an important zoonotic disease globally. In immunocompromised hosts, infection Canbe life-threatening as no effective treatments are currently available to control infection. To increase our understanding of the mechanisms that play a role in host-parasite interactions at the level of the immune response, we investigated the effects of Cryptosporidium parvum antigen (CPA) on bone marrow-derived (DCS). Herein we examined cytokine secretion and cell surface marker expression on DCs exposed to CPA. We also measured cytokine production in CD4+ cells co-cultured with CPA primed DCs in the presence of anti-CD3. CPA induced a significant increase in the production of interleukin(IL)-12p40, IL-10, IL-6, and TNF-α by DCs and enhanced the expression of the cell surface markers TLR4, CD80, CD86, and MHC11. CPA primed DC co-cultured in the presence of anti-CD3 with CD4+ T-cells inhibited the secretion of Th2 associated cytokines, notably IL-5 and IL-13, with no effects on the secretions of interferon (IFN)-γ, IL-2, IL-17, and IL-10. These findings support studies in the literature that CPA can induce the full maturation of DCs that subsequently initiate Th1 immune responses critical to the resolution of C. parvum infection.Keywords: cryptosporidium parvum, dendritic cells, IL-12 p70, cell surface marker
Procedia PDF Downloads 1732247 Anti-Jaundice Properties of Methanolic Extract of Carica Papaya Leaves on Jaundice-Induced Albino Rat
Authors: Joseph Bamidele Minari
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The anti-jaundice properties of the methanolic extract of Carica papaya leaves on albino rat was evaluated. In order to achieve this, the phytochemical screening of the extract was carried out, and carbon tetrachloride (CCl4) (i.p) was injected into albino rats to induce jaundice. The rats were simultaneously given oral doses of 20 mg/kg, 40 mg/kg, 60 mg/kg, 80 mg/kg and 100 mg/kg (p.o) of methanolic extract of C. papaya. The effects of these extract on total bilirubin concentration, liver ALT AST, GGT activities of the jaundice-induced rats were studied after seven days period of the experiment. Administration of CCl4 alone to the rats significantly increased (p<0.05) total bilirubin concentration while the activities of ALT, AST, and GGT in the liver when compared to controls which received distilled water (p.o) was significantly lower (p<0.05). Simultaneous treatment of CCl4 injection, and oral administration of different doses of the C. papaya extract significantly reduced (p<0.05) total bilirubin concentration in the serum while the liver ALT AST, GGT activities significantly increased (p < 0.05). However, the lowest significant reduction (p<0.05) of bilirubin concentration was observed with simultaneous administration of 60mg/kg of the extract on the rats. This study suggests that the extract of C. papaya leaves possess the phytochemicals that have anti-jaundice properties.Keywords: carica papaya, jaundice, herbal medicine, liver, rat
Procedia PDF Downloads 4522246 5-[Aryloxypyridyl (or Nitrophenyl)]-4H-1,2,4-Triazoles as Flexible Benzodiazepine Analogs: Synthesis, Receptor Binding Affinity and the Lipophilicity-Dependent Anti-Seizure Onset of Action
Authors: Latifeh Navidpour, Shabnam Shabani, Alireza Heidari, Manouchehr Bashiri, Azadeh Ebrahim-Habibi, Soraya Shahhosseini, Hamed Shafaroodi, Sayyed Abbas Tabatabai, Mahsa Toolabi
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A new series of 5-(2-aryloxy-4-nitrophenyl)-4H-1,2,4-triazoles and 5-(2-aryloxy-3-pyridyl)-4H-1,2,4-triazoles, possessing C-3 thio or alkylthio substituents, was synthesized and evaluated for their benzodiazepine receptor affinity and anti-seizure activity. These analogues revealed similar to significantly superior affinity to GABAA/ benzodiazepine receptor complex (IC50 values of 0.04–4.1 nM), relative to diazepam as the reference drug (IC50 value of 2.4 nM). To determine the onset of anti-seizure activity, the time-dependent effectiveness of i.p. administration of compounds on pentylenetetrazole induced seizure threshold was studied and a very good relationship was observed between the lipophilicity (cLogP) and onset of action of studied analogues (r2 = 0.964). The minimum effective dose of the compounds, determined at the time the analogues showed their highest activity, was demonstrated to be 0.025–0.1 mg/kg, relative to diazepam (0.025 mg/kg).Keywords: 1, 2, 4-triazole, flexible benzodiazepines, GABAA/bezodiazepine receptor complex, onset of action, PTZ induced seizure threshold
Procedia PDF Downloads 1042245 Exploring Urbanization-Induced Wetland Loss within the Greater Toronto Area from 2005 to 2015
Authors: Kaushika Vinotheeswaran
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The Greater Toronto Area (GTA), located in Ontario, Canada, is among the fastest-growing metropolitan areas in North America. Rapid urbanization within the GTA has led to increased imperviousness and surface runoff, contributing to wetland loss. Wetland cover and land cover data from the Southern Ontario Land Resource Information System were analyzed to characterize wetland loss to built-up areas and land conversions between 2005 and 2015, evaluating the extent of urbanization-induced wetland loss. Spatial analysis revealed a significant increase in the number of wetlands lost from 2005 to 2011 compared to the period from 2011 to 2015, with these losses attributed to increased urban expansions within the GTA. Non-wetland conversions, such as agricultural and impervious built-up uses to support urban expansions, played a significant role in wetland loss. Current approaches to wetland policy implementation and land-use planning strategies do not effectively identify or mitigate damage to wetlands in advance of development, resulting in significant wetland loss. Therefore, wetland conservation policies must be re-evaluated to address gaps in policy practice and focus on minimizing wetland loss.Keywords: wetland loss, urbanization, impervious, pervious, wetland conservation
Procedia PDF Downloads 702244 Roles of Lysine-63-Linked Ubiquitination in Cell Decision Fate between Cell Proliferation and Apoptosis
Authors: Chargui Abderrahman, Nehdi Afef , BelaïD Amine , Djerbi Nadir, Tauc Michel, Hofman Paul, Mograbi Baharia, El May MichèLe
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K63-linked ubiquitination — i.e. conjugation of a chain of ubiquitins (Ub) linked through lys63 — has emerged as a key mechanism regulating signalling transduction pathways. Although critical, very little information is currently available about how subversion of K63 ubiquitination might contribute to cancers and inflammatory diseases. The present study provides the first evidence that Cadmium (Cd), a widespread environmental carcinogen and toxicant, is a powerful activator of K63 ubiquitination. Indeed, Cd induces accumulation of K63 polyUb proteins. Importantly, Cd-induced ubiquitination does not stem on oxidative damage or proteasome impairment. Rather, we demonstrate that Cd not only activates K63 ubiquitination but also amplifies their accumulation by overloading the capacity of autophagy pathway. At molecular level, Cd-induced ubiquitination is correlated with stabilization of HIF-1 and the activation of NF-B, two transcription factors. Strikingly, prolonged cell exposure to high Cd concentrations induces an exaggerated K63 ubiquitination that fosters aggresome formation, thus precluding these proteins from interacting with their downstream nuclear targets. We therefore propose that the aberrant activation of K63 ubiquitination by the carcinogen Cadmium could promote cell proliferation and inflammation at low levels while high levels committed cell to death.Keywords: cadmium, environmental exposure, Lysine-63-ubiquitination, kidney, apoptosis, proliferation, autophagy
Procedia PDF Downloads 2092243 Anti-Obesity Effect of Cordyceps militaris Fermented Black Rice
Authors: Chih-Hung Liang, Jung-Jung Chen, Shen-Shih Chiang
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Obesity is defined as abnormal or excessive fat accumulation that presents a risk to health, which are major risk factors for a number of chronic diseases, including diabetes, cardiovascular diseases and cancer. Cordyceps militaris (CM) is a well-known traditional medicine in Asian countries and a rich source of biologically active components. Black rice (Oryza sativa L.) is a special cultivar of rice that contains rich anthocyanins and regarded as a health-promoting food in China and other Eastern. The aim of this study was to investigate the anti-obesity effect of Cordyceps militaris fermented black rice (CB) on HFD-induced BALB/c mice model. The results indicated that administration of low and high dosage of CB powder significantly reduced the body weights (7.38% and 7.78%), body fat ratio (2.37% and 2.78%), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels compared to the HF group (p<0.05). Histopathological analysis showed that the score of fatty liver in HF group (5.0) was significantly higher than CB groups (2.1 and 3.6) (p<0.05). In conclusion, Cordyceps militaris fermented black rice can reduce the body weight via inhibition of the fat accumulation in liver and body and possess the anti-obesity potency.Keywords: Cordyceps militaris, black rice, obesity, HFD-induced mice
Procedia PDF Downloads 3102242 Immune Modulation and Cytomegalovirus Reactivation in Sepsis-Induced Immunosuppression
Authors: G. Lambe, D. Mansukhani, A. Shetty, S. Khodaiji, C. Rodrigues, F. Kapadia
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Introduction: Sepsis is known to cause impairment of both innate and adaptive immunity and involves an early uncontrolled inflammatory response, followed by a protracting immunosuppression phase, which includes decreased expression of cell receptors, T cell anergy and exhaustion, impaired cytokine production, which may cause high risk for secondary infections due to reduced response to antigens. Although human cytomegalovirus (CMV) is widely recognized as a serious viral pathogen in sepsis and immunocompromised patients, the incidence of CMV reactivation in patients with sepsis lacking strong evidence of immunosuppression is not well defined. Therefore, it is important to determine an association between CMV reactivation and sepsis-induced immunosuppression. Aim: To determine the association between incidence of CMV reactivation and immune modulation in sepsis-induced immunosuppression with time. Material and Methods: Ten CMV-seropositive adult patients with severe sepsis were included in this study. Blood samples were collected on Day 0, and further weekly up to 21 days. CMV load was quantified by real-time PCR using plasma. The expression of immunosuppression markers, namely, HLA-DR, PD-1, and regulatory T cells, were determined by flow cytometry using whole blood. Results: At Day 0, no CMV reactivation was observed in 6/10 patients. In these patients, the median length for reactivation was 14 days (range, 7-14 days). The remaining four patients, at Day 0, had a mean viral load of 1802+2599 copies/ml, which increased with time. At Day 21, the mean viral load for all 10 patients was 60949+179700 copies/ml, indicating that viremia increased with the length of stay in the hospital. HLA-DR expression on monocytes significantly increased from Day 0 to Day 7 (p = 0.001), following which no significant change was observed until Day 21, for all patients except 3. In these three patients, HLA-DR expression on monocytes showed a decrease at elevated viral load (>5000 copies/ml), indicating immune suppression. However, the other markers, PD-1 and regulatory T cells, did not show any significant changes. Conclusion: These preliminary findings suggest that CMV reactivation can occur in patients with severe sepsis. In fact, the viral load continued to increase with the length of stay in the hospital. Immune suppression, indicated by decreased expression of HLA-DR alone, was observed in three patients with elevated viral load.Keywords: CMV reactivation, immune suppression, sepsis immune modulation, CMV viral load
Procedia PDF Downloads 1502241 Effect of Green Coffee Bean Extract on Gentamicin Induced Acute Renal Failure in Rats
Authors: Amina Unis, Samah S. El Basateeny, Noha A. H. Nassef
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Introduction: Acute Renal Failure (ARF) is one of the most common problems encountered in hospitalized critically ill patients. In recent years great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of ARF. Hence, the current study was designed to investigate the effect of Green Coffee Bean Extract (GCBE) on gentamicin induced ARF in rats. Methods: The study was conducted on 60 male rats divided into six equal groups. Group 1 served as normal control group and GCBE was administered for 7 days at a dose of 20 mg/kg/day in group 2 and 40 mg/kg/day in group 3 to test the effect of GCBE on normal kidneys. ARF was induced by a daily intraperitoneal injection of gentamicin (80 mg/kg) for 7 days in group 4 (model group), group 5 (GCBE 20 mg/kg/day) and group 6 (GCBE 20 mg/kg/day). All rats were sacrificed after 7 days and blood was withdrawn for kidney function tests. Kidneys were removed for determination of renal oxidative stress markers and histopathological examination. Results: The present study showed that rats that received oral GCBE for 7 days without induction of ARF showed no significant change in all the assessed parameters in comparison to the normal control group, while rats in the groups that received oral GCBE for 7 days with induction of ARF showed a significant improvement in kidney functions tests (decrease in serum urea, serum creatinine, and blood urea nitrogen) when compared to the ARF model group. Moreover, there was significant amelioration in renal oxidative stress markers (renal malondialdehyde, renal superoxide dismutase) and renal histopathological changes in the GCBE treated groups along induction of ARF when compared to ARF model group. The most significant improvement was reported in the group where GCBE was administered for 7 days in a dose 40 mg/kg/day, along with induction of ARF. Conclusion: GCBE has a potential role in ameliorating renal damage involved in ARF mostly through its antioxidant effect.Keywords: green coffee bean extract, gentamicin, acute renal failure, pharmacology
Procedia PDF Downloads 2922240 A Case Study of Control of Blast-Induced Ground Vibration on Adjacent Structures
Authors: H. Mahdavinezhad, M. Labbaf, H. R. Tavakoli
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In recent decades, the study and control of the destructive effects of explosive vibration in construction projects has received more attention, and several experimental equations in the field of vibration prediction as well as allowable vibration limit for various structures are presented. Researchers have developed a number of experimental equations to estimate the peak particle velocity (PPV), in which the experimental constants must be obtained at the site of the explosion by fitting the data from experimental explosions. In this study, the most important of these equations was evaluated for strong massive conglomerates around Dez Dam by collecting data on explosions, including 30 particle velocities, 27 displacements, 27 vibration frequencies and 27 acceleration of earth vibration at different distances; they were recorded in the form of two types of detonation systems, NUNEL and electric. Analysis showed that the data from the explosion had the best correlation with the cube root of the explosive, R2=0.8636, but overall the correlation coefficients are not much different. To estimate the vibration in this project, data regression was performed in the other formats, which resulted in the presentation of new equation with R2=0.904 correlation coefficient. Finally according to the importance of the studied structures in order to ensure maximum non damage to adjacent structures for each diagram, a range of application was defined so that for distances 0 to 70 meters from blast site, exponent n=0.33 and for distances more than 70 m, n =0.66 was suggested.Keywords: blasting, blast-induced vibration, empirical equations, PPV, tunnel
Procedia PDF Downloads 1312239 Hexavalent Chromium-Induced Changes in Biochemical Parameters of Wistar Albino Rats
Authors: Ounassa Adjroud
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Potassium dichromate (K2Cr2O7) is one of the most toxic elements to which man can be exposed at work or in the environment. The purpose of the current work is to compare the effect of K2Cr2O7 using variations in the dose, route of administration and duration of exposure in male and female Wistar albino rats with a special focus on biochemical parameters. K2Cr2O7 was subcutaneously administered alone (10, 50 and 100 mg/kg body weight) to female Wistar albino rats. Male rats received in their drinking water K2Cr2O7 30 mg/L/day) for 20 consecutive days. The Biochemical parameters were evaluated on days 3, 6 and 21 after subcutaneous (sc.) treatment in female rats and on days 10 and 20 after oral administration in male rats. The subcutaneous (s.c.) administration of 25 mg/kg of K2Cr2O7 to Wistar albino rats induced a slight change in plasma glucose levels during the experiment period. On the contrary, a significant decrease in plasma glucose levels was observed with 50 mg/kg mainly on days 3 (-26%) and 21 (-48%) after treatment compared to controls females rats. On the other hand, the higher dose provoked a significant increase in plasma glucose concentrations on days 6 (+31%) and 21 (+60%). similarly, the lower dose of chromium had no effect on the plasma urea levels. Conversely, a significant increase (122%) in this parameter was obtained during the first three days after treatment. In addition, a significant decrease in plasma glucose levels was observed with 50 mg/kg mainly on days 3 (-26%) and 21 (-48%) after treatment. On the other hand, the higher dose provoked a significant increase in plasma glucose concentrations on days 6 (+31%) and 21 (+60%). similarly, the lower dose of chromium had no effect on the plasma urea levels. Conversely, a significant increase in this parameter (122%) was obtained during the first three days after treatment. In addition, administration of 100 mg/kg of K2Cr2O7 by s.c markedly augmented the levels of plasma urea on days 3 (62%) and 6 (121%). Administration of 30 mg/L/day of K2Cr2O7 in the drinking water induced a significant augmentation in both of plasma glucose (27%) and urea (126%) during the first ten days of treatment. These results suggested that K2Cr2O7 administered subcutaneously or in the drinking water may induce harmful effects on biochemical parameters.Keywords: glucose, potassium dichromate, Wistar albino rat, urea
Procedia PDF Downloads 2832238 Comparison of the Effects of Fresh Leaf, Septum and Peel Extracts of Walnut on Blood Glucose and Pancreatic Structure
Authors: Tahmineh Hasanzadeh, Afshin Farahbakhsh
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There is some report about the hypoglycemic effect of Juglans rejia L. leaf in alloxan induced diabetic rats and hypoglycemic effect of its fruit peel administered intraperitoneally.In Iranian traditional medicine, septum of walnut shell (SWS) was recommended to reduce blood glucose. For this purpose, 41 male bulb/C mice 25-30 gm were divided into five groups. All the animals received IP injection of streptozotocin (STZ) (220 mg/kg). Two weeks later, the diabetic animals were received daily oral treatment of normal saline and aqueous extract of SWS (200, 400, 600 and 800 mg/kg) respectively for four weeks. Blood samples were taken from retro orbital sinus before the start of the experiment and repeated each two weeks. At the end of the experiment, the animals were sacrificed and the pancreatic tissues were fixed, prepared and stained by Hematoxylin-Eosin for light microscope studies. The results showed that in each group, the SWS extract reduced blood glucose in a long time (p < 0.05). metabolic extract in STZ- induced diabetic rats, which was accompanied by the hypoglycemic effect of leaf extract. However, this effect should be determined with scientific researches. Therefore, the aim of this study is to evaluate the effect of the aqueous extract of SWS on blood glucose and histopathological structure of pancreas.Keywords: septum of walnut, blood glucose, pancreas, diabetes, walnut leaf, walnut peel, insulin
Procedia PDF Downloads 2792237 Canthin-6-One Alkaloid Inhibits NF-κB and AP-1 Activity: An Inhibitory Action At Transcriptional Level
Authors: Fadia Gafri, Kathryn Mckintosh, Louise Young, Alan Harvey, Simon Mackay, Andrew Paul, Robin Plevin
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Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor found originally to play a key role in regulating inflammation. However considerable evidence links this pathway to the suppression of apoptosis, cellular transformation, proliferation and invasion (Aggarwal et al., 2006). Moreover, recent studies have also linked inflammation to cancer progression making NF-κB overall a promising therapeutic target for drug discovery (Dobrovolskaia & Kozlov, 2005). In this study we examined the effect of the natural product canthin-6-one (SU182) as part of a CRUK small molecule drug discovery programme for effects upon the NF-κB pathway. Initial studies demonstrated that SU182 was found to have good potency against the inhibitory kappa B kinases (IKKs) at 30M in vitro. However, at concentrations up to 30M, SU182 had no effect upon TNFα stimulated loss in cellular IκBα or p65 phosphorylation in the keratinocyte cell line NCTC2544. Nevertheless, 30M SU182 reduced TNF-α / PMA-induced NF-κB-linked luciferase reporter activity to (22.9 ± 5%) and (34.6± 3 %, P<0.001) respectively, suggesting an action downstream of IKK signalling. Indeed, SU182 neither decreased NF-κB-DNA binding as assayed by EMSA nor prevented the translocation of p65 (NF-κB) to the nucleus assessed by immunofluorescence and subcellular fractionation. In addition to the inhibition of transcriptional activity of TNFα-induced NF-κB reporter activity SU182 significantly reduced PMA-induced AP-1-linked luciferase reporter activity to about (48± 9% at 30M, P<0.001) . This mode of inhibition was not sufficient to prevent the activation of NF-κB dependent induction of other proteins such as COX-2 and iNOS, or activated MAP kinases (p38, JNK and ERK1/2) in LPS stimulated RAW 264.7 macrophages. Taken together these data indicate the potential for SU182 to interfere with the transcription factors NF-κB and AP-1 at transcriptional level. However, no potential anti-inflammatory effect was indicated, further investigation for other NF-κB dependent proteins linked to survival are also required to identify the exact mechanism of action.Keywords: Canthin-6-one, NF-κB, AP-1, phosphorylation, Nuclear translocation, DNA-binding activity, inflammatory proteins.
Procedia PDF Downloads 458