Search results for: high dosage drugs

Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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Authors: Shaoxi Wang, Pouya Rezai

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High aspect ratio is the necessary parts of complex microstructures. Some methods available to achieve high aspect ratio requires expensive materials or complex process; others is difficult to research simple high aspect ratio structures. The paper presents a simple and cheap two-step Polydimethylsioxane (PDMS) transferring process to get high aspect ratio single pillars, which only requires covering the PDMS mold with Brij@52 surface solution. The experimental results demonstrate the method efficiency and effective.

Keywords: high aspect ratio, microstructure, PDMS, Brij

Procedia PDF Downloads 264

Authors: Bekan Bogale, Tsegaye Girma Asere, Tilahun Yai, Fekadu Melak

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Aims: To study photocatalytic degradation of methylene blue dye on cuprous oxide/graphene nanocomposite. Background: Cuprous oxide (Cu2O) nanoparticles are among the metal oxides that demonstrated photocatalytic activity. However, the stability of Cu2O nanoparticles due to the fast recombination rate of electron/hole pairs remains a significant challenge in their photocatalytic applications. This, in turn, leads to mismatching of the effective bandgap separation, tending to reduce the photocatalytic activity of the desired organic waste (MB). To overcome these limitations, graphene has been combined with cuprous oxides, resulting in cuprous oxide/graphene nanocomposite as a promising photocatalyst. Objective: In this study, Cu2O/graphene nanocomposite was synthesized and evaluated for its photocatalytic performance of methylene blue (MB) dye degradation. Method: Cu2O/graphene nanocomposites were synthesized from graphite powder and copper nitrate using the facile sol-gel method. Batch experiments have been conducted to assess the applications of the nanocomposites for MB degradation. Parameters such as contact time, catalyst dosage, and pH of the solution were optimized for maximum MB degradation. The prepared nanocomposites were characterized by using UV-Vis, FTIR, XRD, and SEM. The photocatalytic performance of Cu2O/graphene nanocomposites was compared against Cu2O nanoparticles for cationic MB dye degradation. Results: Cu2O/graphene nanocomposite exhibits higher photocatalytic activity for MB degradation (with a degradation efficiency of 94%) than pure Cu2O nanoparticles (67%). This has been accomplished after 180 min of irradiation under visible light. The kinetics of MB degradation by Cu2O/graphene composites can be demonstrated by the second-order kinetic model. The synthesized nanocomposite can be used for more than three cycles of photocatalytic MB degradation. Conclusion: This work indicated new insights into Cu2O/graphene nanocomposite as high-performance in photocatalysis to degrade MB, playing a great role in environmental protection in relation to MB dye.

Keywords: methylene blue, photocatalysis, cuprous oxide, graphene nanocomposite

Procedia PDF Downloads 189

Authors: Asim Olgun, Ali Kara, Vural Butun, Pelin Sevinc, Merve Gungor, Orhan Ornek

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In this study, we investigated the possibility of using waste containing boron impurity (BW) as an adsorbent for the removal of Orange 16 from aqueous solution. Surface properties of the BW, heat treated BW, and diblock copolymer coated BW were examined by using Zeta Meter and scanning electron microscopy (SEM). The polymer modified sample having the highest positive zeta potential was used as an adsorbent. Batch adsorption studies were carried out. The operating variables studied were the initial dye concentration, contact time, solution pH, and adsorbent dosage. It was found that the dye adsorption largely depends on the initial pH of the solution with maximum uptake occurring at pH 3. The adsorption followed pseudo-second-order kinetics and the isotherm fit well to the Langmuir model.

Keywords: zeta potential, adsorption, Orange 16, isotherms

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Authors: Khaled Sekkoum

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The traditional pharmacopoeia of Algerian Sahara is very rich on vegetable drugs. The great resources and biodiversity of Algerian Sahara flora seem responsible. A survey of medicinal plants used by the local population of the south west of Algeria for the urinary disorders is reported. Sixty-three plant species belonging to thirty-three families were identified. Their botanical and local names, plant part used, mode of use and ailment treated are given.

Keywords: medicinal plants, urinary diseases, Sahara, Algeria

Procedia PDF Downloads 334

Authors: Lacramioara Ochiuz, Manuela Hortolomei, Aurelia Vasile, Iulian Stoleriu, Marcel Popa, Cristian Peptu

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Local antibiotherapy is one of the most effective acne therapies. Erythromycin (ER) is a macrolide antibiotic topically administered for over 30 years in the form of gel, ointment or hydroalcoholic solution for the acne therapy. The use of ER as a base for topical dosage forms raises some technological challenges due to the physicochemical properties of this substance. The main disadvantage of ER is the poor water solubility (2 mg/mL) that limits both formulation using hydrophilic bases and skin permeability. Cyclodextrins (CDs) are biocompatible cyclic oligomers of glucose, with hydrophobic core and hydrophilic exterior. CDs are used to improve the bioavailability of drugs by increasing their solubility and/or their rate of dissolution after including the poorly water soluble substances (such as ER) in the hydrophobic cavity of CDs. Adding CDs leads to the increase of solubility and improved stability of the drug substance, increased permeability of substances of low water solubility, decreased toxicity and even to active dose reduction as a result of increased bioavailability. CDs increase skin tolerability by reducing the irritant effect of certain substances. We have included ER to lactide modified β-cyclodextrin, in order to improve the therapeutic effect of topically administered ER. The aims of the present study were to synthesise and describe a new complex with prolonged release of ER with lactide modified β-cyclodextrin (CD-LA_E), to investigate the CD-LA_E complex by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), to analyse the effect of semisolid base on the in vitro and ex vivo release characteristics of ER in the CD-LA_E complex by assessing the permeability coefficient and the release kinetics by fitting on mathematical models. SEM showed that, by complexation, ER changes its crystal structure and enters the amorphous phase. FTIR analysis has shown that certain specific bands of some groups in the ER structure move during the incapsulation process. The structure of the CD-LA_E complex has a molar ratio of 2.12 to 1 between lactide modified β-cyclodextrin and ER. The three semisolid bases (2% Carbopol, 13% Lutrol 127 and organogel based on Lutrol and isopropyl myristate) show a good capacity for incorporating the CD-LA_E complex, having a content of active ingredient ranging from 98.3% to 101.5% as compared to the declared value of 2% ER. The results of the in vitro dissolution test showed that the ER solubility was significantly increased by CDs incapsulation. The amount of ER released from the CD-LA_E gels was in the range of 76.23% to 89.01%, whereas gels based on ER released a maximum percentage of 26.01% ER. The ex vivo dissolution test confirms the increased ER solubility achieved by complexation, and supports the assumption that the use of this process might increase ER permeability. The highest permeability coefficient was obtained in ER released from gel based on 2% Carbopol: in vitro 33.33 μg/cm2/h, and ex vivo 26.82 μg/cm2/h, respectively. The release kinetics of complexed ER is performed by Fickian diffusion, according to the results obtained by fitting the data in the Korsmeyer-Peppas model.

Keywords: erythromycin, acne, lactide, cyclodextrin

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Authors: Abeer N. Alshukairi, Abdulrahman A. Alrajhi, Abdulfattah W. Alamri, Adel F. Alothman

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We described the nosocomial transmission of a pre-XDR or an MDR case of pulmonary tuberculosis in a HIV negative health care worker in an area endemic for MDR & XDR tuberculosis. With inadequate therapy and non-compliance, his strain developed acquired resistance and he presented with extra-pulmonary XDR tuberculosis in the form of multi-focal osteomyelitis and encysted pleural effusion. He was cured after 2 years of therapy with various anti-tuberculous drugs in addition to interferon gamma.

Keywords: osteomyelitis, treatment, XDR tuberculosis, successful treatment

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Authors: Asiya Mahtab, Sushama Talegaonkar

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The research is aimed at developing targeted lipid-based nanocarrier systems of chondroitin sulfate (CS) to deliver an antirheumatic drug to the inflammatory site in arthritic paw. Lipid-based nanoparticle (TEF-lipo) was prepared by using a thin-film hydration method. The coating of prepared drug-loaded nanoparticles was done by the ionic interaction mechanism. TEF-lipo and CS-coated lipid nanoparticle (CS-lipo) were characterized for mean droplet size, zeta potential, and surface morphology. TEF-lipo and CS-lipo were further subjected to in vitro cell line studies on RAW 264.7 murine macrophage, U937, and MG 63 cell lines. The pharmacodynamic study was performed to establish the effectiveness of the prepared lipid-based conventional and targeted nanoparticles in comparison to pure drugs. Droplet size and zeta potential of TEF-lipo were found to be 128. 92 ± 5.42 nm and +12.6 ± 1.2 mV. It was observed that after the coating of TEF-lipo with CS, particle size increased to 155.6± 2.12 nm and zeta potential changed to -10.2± 1.4mV. Transmission electron microscopic analysis revealed that the nanovesicles were uniformly dispersed and detached from each other. Formulations followed sustained release pattern up to 24 h. Results of cell line studies ind icated that CS-lipo formulation showed the highest cytotoxic potential, thereby proving its enhanced ability to kill the RAW 264.7 murine macrophage and U937 cells when compared with other formulations. It is clear from our in vivo pharmacodynamic results that targeted nanocarriers had a higher inhibitory effect on arthritis progression than nontargeted nanocarriers or free drugs. Results demonstrate that this approach will provide effective treatment for rheumatoid arthritis, and CS served as a potential prophylactic against the advancement of cartilage degeneration.

Keywords: adjuvant induced arthritis, chondroitin sulfate, rheumatoid arthritis, teriflunomide

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Authors: Maria I. Nuñez-Hernández, Maria L. Riesco

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Background: Exclusive breastfeeding (EBF) up to 6 months old infant have been considered one of the most important factors in the overall development of children. Nevertheless, as resources are scarce, it is essential to identify the most vulnerable groups that have major risk of EBF abandonment, in order to deliver the best strategies. Children of adolescent mothers are within these groups. Aims: To determine the EBF abandonment rate among adolescent mothers and to analyze the associated factors. Methods: Prospective cohort study of adolescent mothers in the southern area of Santiago, Chile, conducted in primary care services of public health system. The cohort was established from 2014 to 2015, with a sample of 105 adolescent mothers and their children at 2 months of life. The inclusion criteria were: adolescent mother from 14 to 19 years old; not twin babies; mother and baby leaving the hospital together after birthchild; correct attachment of the baby to the breast; no difficulty understanding the Spanish language or communicating. Follow-up was performed at 4 and 6 months old infant. Data were collected by interviews, considering EBF as breastfeeding only, without adding other milk, tea, juice, water or other product that not breast milk, except drugs. Data were analyzed by descriptive and inferential statistics, by Kaplan-Meier estimator and Log-Rank test, admitting the probability of occurrence of type I error of 5% (p-value = 0.05). Results: The cumulative EBF abandonment rate at 2, 4 and 6 months was 33.3%, 52.2% and 63.8%, respectively. Factors associated with EBF abandonment were maternal perception of the quality of milk as poor (p < 0.001), maternal perception that the child was not satisfied after breastfeeding (p < 0.001), use of pacifier (p < 0.001), maternal consumption of illicit drugs after delivery (p < 0.001), mother return to school (p = 0.040) and presence of nipple trauma (p = 0.045). Conclusion: EBF abandonment rate was higher in the first 4 months of life and is superior to the population of women who breastfeed. Among the EBF abandonment factors, one of them is related to the adolescent condition, and two are related to the maternal subjective perception.

Keywords: adolescent, breastfeeding, midwifery, nursing

Procedia PDF Downloads 321

Authors: Said Ghalem

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Honey is primarily composed of sugars: glucose and fructose. Depending honey, it's either fructose or glucose predominates. More the fructose concentration and the less the glycemic index (GI) is high. Thus, changes in the insulin response shows a decrease of the amount of insulin secreted at an increased fructose honey. Honey is also a compound that can reduce the lipid in the blood. Several studies on animals, but which remain to be checked in humans, have shown that the honey can have interesting effects when combined with other molecules: associated with Metformin (a medicine taken by diabetics), it shows the benefits and effects of diabetes preserves the tissue; associated ginger, it increases the antioxidant activity and thus avoids neurologic complications, neuropathic. Molecular modeling techniques are widely used in chemistry, biology, and the pharmaceutical industry. Most of the currently existing drugs target enzymes. Inhibition of DPP-4 is an important approach in the treatment of type 2 diabetes. We have chosen for the inhibition of DPP-4 the following molecules: Linagliptin (BI1356), Sitagliptin (Januvia), Vildagliptin, Saxagliptin, Alogliptin, and Metformin (Glucophage), that are involved in the disease management of type 2 diabetes and added to honey. For this, we used software Molecular Operating Environment. A Wistar rat study was initiated in our laboratory with a well-studied protocol; after sacrifice, according to international standards and respect for the animal This theoretical approach predicts the mode of interaction of a ligand with its target. The honey can have interesting effects when combined with other molecules, it shows the benefits and effects of honey preserves the tissue, it increases the antioxidant activity, and thus avoids neurologic complications, neuropathic or macrovascular. The organs, especially the kidneys of Wistar, shows that the parameters to renal function let us conclude that damages caused by diabetes are slightly perceptible than those observed without the addition of a high concentration of fructose honey.

Keywords: honey, molecular modeling, DPP4 enzyme, metformin

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Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Javaid Irfan, Andreas G. Schätzlein, Ijeoma F Uchegbeu

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Development of efficient delivery system for hydrophobic drugs remains a major concern in chemotherapy. The objective of the current study was to develop polymeric drug-delivery system for etoposide from amphiphilic derivatives of glycol chitosan, capable to improve the pharmacokinetics and to reduce the adverse effects of etoposide due to various organic solvents used in commercial formulations for solubilisation of etoposide. As a promising carrier, amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxy succinimide and quaternisation to glycol chitosan backbone. To this end a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternisation into 13 kDa. Nano sized micelles prepared from this amphiphilic polymer had the capability to encapsulate up to 3 mg/ml etoposide. The pharmacokinetic results indicated that GCPQ based etoposide formulation transformed the biodistribution pattern. AUC 0.5-24 hr showed statistically significant difference in ETP-GCPQ vs. commercial preparation in liver (25 vs 70, p<0.001), spleen (27 vs. 36, P<0.05), lungs (42 vs. 136, p<0.001), kidneys (25 vs. 30, p<0.05) and brain (19 vs. 9,p<0.001). Using the hydrophobic fluorescent dye Nile red, we showed that micelles efficiently delivered their payload to MCF7 and A2780 cancer cells in-vitro and to A431 xenograft tumor in-vivo, suggesting these systems could deliver hydrophobic anti- cancer drugs such as etoposide to tumors. The pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drug after intravenous administration. GCPQ based formulations not only reduced side effects associated with current available formulations but also increased their transport through the biological barriers, thus making it a good delivery system.

Keywords: glycol chitosan, Nile red, micelles, etoposide, A431 xenografts

Procedia PDF Downloads 310

Authors: Anika Chebrolu

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Mono-targeted drugs can be of limited efficacy against complex diseases. Recently, multi-target drug design has been approached as a promising tool to fight against these challenging diseases. However, the scope of current computational approaches for multi-target drug design is limited. DeepLig presents a de-novo drug discovery platform that uses reinforcement learning to generate and optimize novel, potent, and multitargeted drug candidates against protein targets. DeepLig’s model consists of two networks in interplay: a generative network and a predictive network. The generative network, a Stack- Augmented Recurrent Neural Network, utilizes a stack memory unit to remember and recognize molecular patterns when generating novel ligands from scratch. The generative network passes each newly created ligand to the predictive network, which then uses multiple Graph Attention Networks simultaneously to forecast the average binding affinity of the generated ligand towards multiple target proteins. With each iteration, given feedback from the predictive network, the generative network learns to optimize itself to create molecules with a higher average binding affinity towards multiple proteins. DeepLig was evaluated based on its ability to generate multi-target ligands against two distinct proteins, multi-target ligands against three distinct proteins, and multi-target ligands against two distinct binding pockets on the same protein. With each test case, DeepLig was able to create a library of valid, synthetically accessible, and novel molecules with optimal and equipotent binding energies. We propose that DeepLig provides an effective approach to design multi-targeted drug therapies that can potentially show higher success rates during in-vitro trials.

Keywords: drug design, multitargeticity, de-novo, reinforcement learning

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Authors: Mohd Salim Mahtab, Izharul Haq Farooqi, Anwar Khursheed

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Advanced oxidation processes (AOPs) based on Fenton are versatile options for treating complex wastewaters containing refractory compounds. However, the classical Fenton process (CFP) has limitations, such as high sludge production and reagent dosage, which limit its broad use and result in secondary contamination. As a result, long-term solutions are required for process intensification and the removal of these impediments. This study shows that Fenton sludge could serve as a catalyst in the Fe³⁺/Fe²⁺ reductive pathway, allowing non-regenerated sludge to be reused for complex wastewater treatment, such as landfill leachate treatment, even in the absence of Fenton's reagents. Experiments with and without pH adjustments in stages I and II demonstrated that an acidic pH is desirable. Humic compounds in leachate could improve the cycle of Fe³⁺/Fe²⁺ under optimal conditions, and the chemical oxygen demand (COD) removal efficiency was 22±2% and 62±2%% in stages I and II, respectively. Furthermore, excellent total suspended solids (TSS) removal (> 95%) and color removal (> 80%) were obtained in stage II. The processes underlying synergistic (oxidation/coagulation/adsorption) effects were addressed. The design of the experiment (DOE) is growing increasingly popular and has thus been implemented in the chemical, water, and environmental domains. The relevance of the statistical model for the desired response was validated using the explicitly stated optimal conditions. The operational factors, characteristics of reused sludge, toxicity analysis, cost calculation, and future research objectives were also discussed. Reusing non-regenerated Fenton sludge, according to the study's findings, can minimize hazardous solid toxic emissions and total treatment costs.

Keywords: advanced oxidation processes, catalysis, Fe³⁺/Fe²⁺ cycle, fenton sludge

Procedia PDF Downloads 89

Authors: Farah Diab, Mohamad Khalil, Francesca Storace, Francesca Baldini, Piero Portincasaa, Giulio Lupidi, Laura Vergani

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Thymbra spicata is a thyme-like plant belonging to the Lamiaceae family that shows a global distribution, especially in the eastern Mediterranean region. Leaves of T. spicata contain large amounts of phenols such as phenolic acids (rosmarinic acid), phenolic monoterpenes (carvacrol), and flavonoids. In Lebanon, T. spicata is currently used as a culinary herb in salad and infusion, as well as for traditional medicinal purposes. Carvacrol (5-isopropyl-2-methyl phenol), the most abundant polyphenol in the organic extract and essential oils, has a great array of pharmacological properties. In fact, carvacrol is largely employed as a food additive and neutraceutical agent. Our aim is to investigate the beneficial effects of T. spicata ethanolic extract (TE) and its main component, carvacrol, using in vitro models of hepatic steatosis and endothelial dysfunction. As a further point, we focused on investigating if and how the binding of carvacrol to albumin, the physiological transporter for drugs in the blood, might be altered by the presence of high levels of fatty acids (FAs), thus impairing the carvacrol bio-distribution in vivo. For that reason, hepatic FaO cells treated with exogenous FAs such as oleate and palmitate mimic hepatosteatosis; endothelial HECV cells exposed to hydrogen peroxide are a model of endothelial dysfunction. In these models, we measured lipid accumulation, free radical production, lipoperoxidation, and nitric oxide release before and after treatment with carvacrol. The carvacrol binding to albumin with/without high levels of long-chain FAs was assessed by absorption and emission spectroscopies. Our findings show that both TE and carvacrol (i) counteracted lipid accumulation in hepatocytes by decreasing the intracellular and extracellular lipid contents in steatotic FaO cells; (ii) decreased oxidative stress in endothelial cells by significantly reducing lipoperoxidation and free radical production, as well as, attenuating the nitric oxide release; (ii) high levels of circulating FAs reduced the binding of carvacrol to albumin. The beneficial effects of TE and carvacrol on both hepatic and endothelial cells point to a nutraceutical potential. However, high levels of circulating FAs, such as those occurring in metabolic disorders, might hinder the carvacrol transport, bio-distribution, and pharmacodynamics.

Keywords: carvacrol, endothelial dysfunction, fatty acids, non-alcoholic fatty liver diseases, serum albumin

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Authors: Rajendra Jangde, Deependra Singh

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Present work was based with objective to release of the antimicrobial and debriding agent in sustained manner at the wound surface. In order to provide a long-lasting antimicrobial action and moist environment on wound space, Biocompatible moist system was developed for complete healing. In the present study, a biocompatible moist system of PVA-gelatin hydrogel was developed capable of carrying multiple drugs- Quercetin and Cabopol in controlled manner for effective and complete wound healing. Carbopol and Quercetin were prepared by thin film hydration techniques and optimized system was incorporated in PVA-Gelatin slurry. PVA-Gelatin hydrogels were prepared by freeze thaw method. The prepared dispersion was casted into films to prepare multiphase hydrogel system and characterized by in vitro and in vivo studies. Results revealed the uniform dispersion of microspheres in a three-dimensional matrix of the PVA-Gelatin hydrogel observed at different magnifications. The in vitro release data showed typical biphasic release pattern, i.e., a burst release followed by a slower sustained release for 5 days. Prepared system was found to be stable under both normal and accelerated conditions. Histopathological study showed significant (p<0.05) increase in fibroblast cells, collagen fibres and blood vessels formation. All parameters such as wound contraction, tensile strength, histopathological and biochemical parameters- hydroxyproline content, protein level, etc. were observed significant (p<0.05) in comparison to control group. Present results suggest an accelerated re-epithelialization under moist wound environment with delivery of multiple drugs effective at different stages of wound healing cascade with minimum disturbance of wound bed.

Keywords: multiphase hydrogel, optimization quercetin, wound healing

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Authors: Labiba Zerari Bourafa, Djebar Mohamed Reda, Berrebah Houria, Khadri Sihem, Chiheb Linda

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The study of the effect of metal dust (pollutants) was performed on higher plant white beans Phaseolus vulgaris; the experience took place in cellular toxicology laboratory (in vitro culture). The seeds of the bean Phaseolus vulgaris are cultured in a metal contaminated dust medium (a single treatment by different increasing doses), at a rate of 10 seeds per box, for 10 days. The measurement of morpho-metric parameters is performed during the first 96 hours that follow the germination; while the dosage of the proline, the protein content and histological sections are formed on the tenth day (240 h). All morpho-metric and biochemical parameters measured were highly disturbed by metal dust; histological sections confirm this disurbance.

Keywords: conductive fabrics, metal dust, osmoticums, roots, Phaseolus vulgaris

Procedia PDF Downloads 376

Authors: Chukwudalu C. Nwazojie, Wole W. Soboyejo, John Obayemi, Ali Salifu Azeko, Sandra M. Jusu, Chinyerem M. Onyekanne

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The conventional methods for the diagnosis and treatment of breast cancer include bulk systematic mammography, ultrasound, dynamic contrast-enhanced fast 3D gradient-echo (GRE) magnetic resonance imaging (MRI), surgery, chemotherapy, and radiotherapy. However, nanoparticles and drug-loaded polymer microspheres for disease (cancer) targeting and treatment have enormous potential to enhance the approaches that are used today. The goal is to produce an implantable biomedical device for localized breast cancer drug delivery within Africa and the world. The main advantage of localized delivery is that it reduces the amount of drug that is needed to have a therapeutic effect. Polymer blends of poly (D,L-lactide-co-glycolide) (PLGA) and polycaprolactone (PCL), which are biodegradable, is used as a drug excipient. This work focuses on the development of PLGA-PCL (poly (D,L-lactide-co-glycolide) (PLGA) blended with based injectable drug microspheres and are loaded with anticancer drugs (prodigiosin (PG), and paclitaxel (PTX) control) and also the conjugated forms of the drug functionalized with LHRH (luteinizing hormone-releasing hormone) (PG-LHRH, and PTX- LHRH control), using a single-emulsion solvent evaporation technique. The encapsulation was done in the presence of PLGA-PCL (as a polymer matrix) and poly-(vinyl alcohol) (PVA) (as an emulsifier). Comparative study of the various drugs release kinetics and degradation mechanisms of the PLGA-PCL with an encapsulated drug is achieved, and the implication of this study is for the potential application of prodigiosin PLGA-PCL loaded microparticles for controlled delivery of cancer drug and treatment to prevent the regrowth or locoregional recurrence, following surgical resection of triple-negative breast tumor.

Keywords: cancer, polymers, drug kinetics, nanoparticles

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Authors: Yeşim Tosun, Remzi Şahin

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This paper presents results of compressive strength, capillary water absorption, and density tests conducted on concrete containing recycled aggregate (RCA) which is obtained from structural waste generated by the construction industry in Turkey. In the experiments, 0%, 15%, 30%, 45% and 60% of the normal (natural) coarse aggregate was replaced by the recycled aggregate. Maximum aggregate particle sizes were selected as 16 mm, 22,4 mm and 31,5 mm; and 0,06%, 0,13% and 0,20% of air-entraining agent (AEA) were used in mixtures. Fly ash and superplasticizer were used as a mineral and chemical admixture, respectively. The same type (CEM I 42.5) and constant dosage of cement were used in the study. Water/cement ratio was kept constant as 0.53 for all mixture. It was concluded that capillary water absorption, compressive strength, and density of concrete decreased with increasing RCA ratio. Increasing in maximum aggregate particle size and amount of AEA also affect the properties of concrete significantly.

Keywords: capillary water absorption, compressive strength, recycled concrete aggregates

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Authors: Godwin Ojochogu Adejo, Evelyn UnekwuOjo Adejo, Sunday UnenwOjo Adejo

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The mainstream contemporary approach to controlling the impact of diseases among poultry birds rely largely on curative measures through the administration of drugs to infected birds. Most times as observed in the deep liter poultry farming system, entire flocks including uninfected birds receive the treatment they do not need. As such, unguarded use of chemical drugs and antibiotics has led to wastage and accumulation of chemical residues in poultry products with associated health hazards to humans. However, wanton and frequent drug usage in poultry is avoidable if feeding and drinking equipment are designed to curb infection transmission among birds. Using toxicological assays as guide and with efficiency and simplicity in view, two newly field-tested and recently patented equipments called 'healthy liquid drinking trough (HDT)' and 'healthy feeding trough (HFT)' that systematically eliminate contamination of the feeding and drinking channels, thereby, curbing wide-spread infection and transmission of diseases in the (intensive) deep litter poultry farming system were designed. Upon combined usage, they automatically and drastically reduced both the amount and frequency of antibiotics use in poultry by over > 50%. Additionally, they conferred optimization of feed and water utilization/elimination of wastage by > 80%, reduced labour by > 70%, reduced production cost by about 15%, and reduced chemical residues in poultry meat or eggs by > 85%. These new and cheap technologies which require no energy input are likely to elevate safety of poultry products for consumers' health, increase marketability locally and for export, and increase output and profit especially among poultry farmers and poor people who keep poultry or inevitably utilize poultry products in developing countries.

Keywords: healthy, trough, toxicological, assay-guided, poultry

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Authors: Manely Ansary Mood, Farzaneh Aziizi, Mahmoud Akbarian

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This investigation included 130 cats diagnosed with FIP (Feb 2021-March 2022) in Iran, 74 with effusive FIP, and 56 with non-effusive FIP. The patients' initial dosage regime consisted of a subcutaneous injection of GS-441524 was 6-15mg/kg-every 24h (based on the wet or ocular and neurologic signs). The minimum treatment period was twelve weeks, extended in animals that still had abnormal lab values, clinical signs, and sonographic findings. The outcomes of the 130 cats that completed the duration of treatment (14 died, 116 cured) were checked and recorded. Clinical, sonographic, and laboratory responses were checked and compared on days 28, 56, and 83 of treatment. 2 of the 116 cured cats relapsed within observation days. At the time of this publication (May 2022), 114 of the studied patients remained healthy. We could conclude that GS-441524 appears to be an effective option for FIP treatment, and also, to the base of our knowledge, this is the first report for group treatment of infected cats of FIP with GS-441524 in Iran.

Keywords: FIP, cat, GS-441524, treatment

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Authors: Elena Kokkoni, Prasanna Kannappan, Ashkan Zehfroosh, Effrosyni Mavroudi, Kristina Strother-Garcia, James C. Galloway, Jeffrey Heinz, Rene Vidal, Herbert G. Tanner

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Early immobility affects the motor, cognitive, and social development. Current pediatric rehabilitation lacks the technology that will provide the dosage needed to promote mobility for young children at risk. The addition of socially assistive robots in early interventions may help increase the mobility dosage. The aim of this study is to examine the feasibility of an early intervention paradigm where non-walking infants experience independent mobility while socially interacting with robots. A dynamic environment is developed where both the child and the robot interact and learn from each other. The environment involves: 1) a range of physical activities that are goal-oriented, age-appropriate, and ability-matched for the child to perform, 2) the automatic functions that perceive the child’s actions through novel activity recognition algorithms, and decide appropriate actions for the robot, and 3) a networked visual data acquisition system that enables real-time assessment and provides the means to connect child behavior with robot decision-making in real-time. The environment was tested by bringing a two-year old boy with Down syndrome for eight sessions. The child presented delays throughout his motor development with the current being on the acquisition of walking. During the sessions, the child performed physical activities that required complex motor actions (e.g. climbing an inclined platform and/or staircase). During these activities, a (wheeled or humanoid) robot was either performing the action or was at its end point 'signaling' for interaction. From these sessions, information was gathered to develop algorithms to automate the perception of activities which the robot bases its actions on. A Markov Decision Process (MDP) is used to model the intentions of the child. A 'smoothing' technique is used to help identify the model’s parameters which are a critical step when dealing with small data sets such in this paradigm. The child engaged in all activities and socially interacted with the robot across sessions. With time, the child’s mobility was increased, and the frequency and duration of complex and independent motor actions were also increased (e.g. taking independent steps). Simulation results on the combination of the MDP and smoothing support the use of this model in human-robot interaction. Smoothing facilitates learning MDP parameters from small data sets. This paradigm is feasible and provides an insight on how social interaction may elicit mobility actions suggesting a new early intervention paradigm for very young children with motor disabilities. Acknowledgment: This work has been supported by NIH under grant #5R01HD87133.

Keywords: activity recognition, human-robot interaction, machine learning, pediatric rehabilitation

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Authors: A. Adetutu, T. M. Awodugba, O. A. Owoade

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The development of resistance to currently known conventional anti-typhoid drugs has necessitated search into cheap, more potent and less toxic anti-typhoid drugs of plant origin. Therefore, this study investigated the anti-typhoid activity of fractions of A. indica in Salmonella typhi infected rats. Leaves of A. indica were extracted in methanol and fractionated into n-hexane, chloroform, ethyl-acetate, and aqueous fractions. The anti-salmonella potentials of fractions of A. indica were assessed via in-vitro inhibition of S. typhi using agar well diffusion, Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and biofilm assays. The biochemical and haematological parameters were determined by spectrophotometric methods. The histological analysis was performed using Haematoxylin and Eosin staining methods. Data analysis was performed by one-way ANOVA. Results of this study showed that S. typhi was sensitive to aqueous and chloroform fractions of A. indica, and the fractions showed biofilm inhibition at concentrations of 12.50, 1.562, and 0.39 mg/mL. In the in-vivo study, the extract and chloroform fraction had significant (p < 0.05) effects on the number of viable S. typhi recovered from the blood and stopped salmonellosis after 6 days of treatment of rats at 500 mg/kg b.w. Treatments of infected rats with chloroform and aqueous fractions of A. indica normalized the haematological parameters in the animals. Similarly, treatment with fractions of the plants sustained a normal antioxidant status when compared with the normal control group. Chloroform and ethyl-acetate fractions of A. indica reversed the liver and intestinal degeneration induced by S. typhi infection in rats. The present investigation indicated that the aqueous and chloroform fractions of A. indica showed the potential to provide an effective treatment for salmonellosis, including typhoid fever. The results of the study may justify the ethno-medicinal use of the extract in traditional medicine for the treatment of typhoid and salmonella infections.

Keywords: Azadirachta indica L, salmonella, typhoid, leave fractions

Procedia PDF Downloads 132

Authors: Muhammad Imran Din

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The aim of this study was to understand the interaction between multi-walled carbon nano tubes (MCNTs) and anticancer agents and evaluate the drug-loading ability of MCNTs. Batch adsorption experiments were carried out for adsorption of 5-Fluorouracil (5-FL) using MCNTs. The effect of various operating variables, viz., adsorbent dosage, pH, contact time and temperature for adsorption of 5-Fluorouracil (5-FL) has been studied. The Freundlich adsorption model was successfully employed to describe the adsorption process. It was found that the pseudo-second-order mechanism is predominant and the overall rate of the 5-Fluorouracil (5-FL) adsorption process appears to be controlled by the more than one-step. Thermodynamic parameters such as free energy change (ΔG°), enthalpy change (ΔH°) and entropy change (ΔS°) have been calculated respectively, revealed the spontaneous, endothermic and feasible nature of adsorption process. The results showed that carbon nano tubes were able to form supra molecular complexes with 5-Fluorouracil (5-FL) by π-π stacking and possessed favorable loading properties as drug carriers.

Keywords: drug, adsorption, anticancer, 5-Fluorouracil (5-FL)

Procedia PDF Downloads 361

Authors: Gansukh Erdenedelger, Doljinsuren Sukhbaatar, Trung Dung Dao, Byeong-Kyu Lee, Han Mo Jeong

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Two kinds of carboxylated thermally reduced graphenes (C-TRGs) having different lateral sizes are examined as a Pickering stabilizer in the suspension polymerization of methyl methacrylate. The size and the shape of the prepared composite particles are irregular due to agglomeration, more evidently when the larger C-TRG is used. In addition, C-TRG is distributed not only on the surface but also inside the composite particles. It indicates that the C-TRG alone is not a stable Pickering agent. However, a very small dosage of acrylic acid remedies all these issues, because acrylic acid interacts with C-TRG and synergizes the stabilizing effect. The compression molded composite of the core/shell poly(methyl methacrylate)/C-TRG particles exhibits a very low percolation threshold of electrical conductivity of 0.03 vol%. It demonstrates that the C-TRG shells of the composite particles effectively form a segregated conductive network throughout the composite.

Keywords: pickering, graphene, polymerization, PMMA

Procedia PDF Downloads 297

Authors: K. M. S. Weerasinghe, A. H. K. Balasooriya, S. L. Ransingha, G. D. Krishantha, R. S. Brhakamanagae, L. C. Wijethilke

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Tomato (Lycopersicon esculentum Mill.) is a major horticultural crop with an estimated global production of over 120 million metric tons and ranks first as a processing crop. The average tomato productivity in Sri Lanka (11 metric tons/ha) is much lower than the world average (24 metric tons/ha).To meet the tomato demand for the increasing population the productivity has to be intensified through the agronomic-techniques. Nutrition is one of the main factors which govern the growth and yield of tomato and the main nutrient source soil affect the plant growth and quality of the produce. Continuous cropping, improper fertilizer usage etc., cause widespread nutrient deficiencies. Therefore synthetic fertilizers and organic manures were introduced to enhance plant growth and maximize the crop yields. In this study, effects of macro and micronutrient supplementations on improvement of growth and yield of tomato were investigated. Selected tomato variety is Maheshi and plants were grown in Regional Agricultural and Research Centre Makadura under the Department of Agriculture recommended (DOA) macro nutrients and various combination of Ontario recommended dosages of secondary and micro fertilizer supplementations. There were six treatments in this experiment and each treatment was replicated in three times and each replicate consisted of six plants. Other than the DOA recommendation, five combinations of Ontario recommended dosage of secondary and micronutrients for tomato were also used as treatments. The treatments were arranged in a Randomized Complete Block Design. All cultural practices were carried out according to the DOA recommendations. The mean data was subjected to the statistical analysis using SAS package and mean separation (Duncan’s Multiple Range test at 5% probability level) procedures. Secondary and micronutrients containing treatments significantly increased most of the growth parameters. Plant height, plant girth, number of leaves, leaf area index etc. Fruits harvested from pots amended with macro, secondary and micronutrients performed best in terms of total yield; yield quality; to pots amended with DOA recommended dosage of fertilizer for tomato. It could be due to the application of all essential macro and micro nutrients that rise in photosynthetic activity, efficient translocation and utilization of photosynthates causing rapid cell elongation and cell division in actively growing region of the plant leading to stimulation of growth and yield were caused. The experiment revealed and highlighted the requirements of essential macro, secondary and micro nutrient fertilizer supplementations for tomato farming. The study indicated that, macro and micro nutrient supplementation practices can influence growth and yield performances of tomato fruits and it is a promising approach to get potential tomato yields.

Keywords: macro and micronutrients, tomato, SAS package, photosynthates

Procedia PDF Downloads 474

Authors: K. Srujana, Vinay U. Rao, M. Sudhakar

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Isoniazide (INH) a freely water soluble and pyrazinamide (Z) a practically water insoluble first line anti tubercular (TB) drugs were identified as candidates for optimizing the Moisture Activated Dry Granulation (MADG) process. The work focuses on identifying the effect of binder type and concentration as well as the effect of magnesium stearate level on critical quality attributes of Disintegration time (DT) and in vitro dissolution test when the tablets are processed by the MADG process. Also, the level of the drug concentration, binder concentration and fluid addition during the agglomeration stage of the MADG process was evaluated and optimized. For INH, it was identified that for tablets with HPMC as binder at both 2% w/w and 5% w/w level and Magnesium stearate upto 1%w/w as lubrication the DT is within 1 minute and the dissolution rate is the fastest (> 80% in 15 minutes) as compared to when PVP or pregelatinized starch is used as binder. Regarding the process, fast disintegrating and rapidly dissolving tablets are obtained when the level of drug, binder and fluid uptake in agglomeration stage is 25% w/w 0% w/w binder and 0.033%. w/w. At the other 2 levels of these three ingredients, the DT is significantly impacted and dissolution is also slower. For pyrazinamide,it was identified that for the tablets with 2% w/w level of each of PVP as binder and Cross Caramellose Sodium disintegrant the DT is within 2 minutes and the dissolution rate is the fastest(>80 in 15 minutes)as compared to when HPMC or pregelatinized starch is used as binder. This may be attributed to the fact that PVP may be acting as a solubilizer for the practically insoluble Pyrazinamide. Regarding the process,fast dispersing and rapidly disintegrating tablets are obtained when the level of drug, binder and fluid uptake in agglomeration stage is 10% w/w,25% w/w binder and 1% w/w.At the other 2 levels of these three ingredients, the DT is significantly impacted and dissolution is comparatively slower and less complete.

Keywords: agglomeration stage, isoniazide, MADG, moisture distribution stage, pyrazinamide

Procedia PDF Downloads 239

Authors: Michelle V. Tomczak, Reyhaneh Bakhtiari, Aaron Granley, Anthony Singhal

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Objective: Cannabis and cocaine are associated with a range of mental and physical effects that can impair aspects of human behavior. Driving is a complex cognitive behavior that is an essential part of everyday life and can be broken down into many subcomponents, each of which can uniquely impact road safety. With the growing movement of jurisdictions to legalize cannabis, there is an increased focus on impairment and driving. The purpose of this study was to identify driving-related cognitive-performance deficits that are impacted by recreational drug use. Design and Methods: With the assistance of law enforcement agencies, we recruited over 300 participants under the influence of various drugs including cannabis and cocaine. These individuals performed a battery of computer-based tasks scientifically proven to be re-lated to on-road driving performance and designed to test response-speed, memory processes, perceptual-motor skills, and decision making. Data from a control group with healthy non-drug using adults was collected as well. Results: Compared to controls, the drug group showed def-icits in all tasks. The data also showed clear differences between the cannabis and cocaine groups where cannabis users were faster, and performed better on some aspects of the decision-making and perceptual-motor tasks. Memory performance was better in the cocaine group for simple tasks but not more complex tasks. Finally, the participants who consumed both drugs performed most similarly to the cannabis group. Conclusions: Our results show distinct and combined effects of cannabis and cocaine on human performance relating to driving. These dif-ferential effects are likely related to the unique effects of each drug on the human brain and how they distinctly contribute to mental states. Our results have important implications for road safety associated with driver impairment.

Keywords: driving, cognitive impairment, recreational drug use, cannabis and cocaine

Procedia PDF Downloads 126

Authors: Sweta Agrawal, Sachin Chaugule, Gargi Rane, Shashank More, Madhavi Indap

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Angiogenesis and metastasis are two of the most important hallmarks of cancer. Hence, most of the cancer therapies nowadays are multi-targeted so as to reduce resistance and have better efficacy. As synthetic molecules arise with a burden of their toxicities and side-effects, more and more research is being focussed on exploiting the vast natural resources of drugs, in the form of plants and animals. Although, the idea of using marine organisms as a source of pharmaceuticals is not new, the pace at which marine drugs are being discovered, has definitely up surged! In the present study, we have assessed the anti-angiogenic and in vitro anti-metastatic activity of aqueous fraction from the extract of marine gastropod Euchelus asper. The soft body of Euchelus Asper was extracted with methanol and named EAME. Partition chromatography of EAME gave three fractions EAME I, II and III. Biochemical analysis revealed the presence of proteins in EAME III. Preliminary analysis had revealed the anti-angiogenic activity was exhibited by EAME III out of the three fractions. Hereafter, EAME III (concentration 25µg/ml-400µg/ml) was tested on chick chorioallantoic membrane (CAM) model for the detailed analysis of its potential anti-angiogenic effect. In vitro testing of the fraction (concentration 0.25µg/ml - 1µg/ml), involved cytotoxicity by SRB assay, cell cycle analysis by flow cytometry and anti-proliferative effect by scratch wound healing assay on A549 lung carcinoma cells. Apart from this, a portion of treated CAM as well as conditioned medium from treated A549 were subjected to gelatin zymography for assessment of matrix metalloproteinases MMP-2 and MMP-9 levels. Our results revealed that EAME III exhibited significant anti-angiogenic activity on CAM which was also supported by histological observations. During histological studies of CAM, it was found that EAME III caused reduction in angiogenesis by altering the extracellular matrix of the CAM membrane. In vitro analysis disclosed that EAME III exhibited moderate cytotoxic effect on A549 cells and its effect was not dose-dependent. The results of flow cytometry confirmed that EAME III caused cell cycle arrest in A549 cell line as almost all of the treated cells were found in G1 phase. Further, the migration and proliferation of A549 was significantly reduced by EAME III as observed from the scratch wound assay. Moreover, Gelatin zymography analysis revealed that EAME III caused suppression of MMP-2 in CAM membrane and reduced MMP-9 and MMP-2 expression in A549 cells. This verified that the anti-angiogenic and anti-metastatic effects of EAME III were correlated with the suppression of MMP-2 and -9. To conclude, EAME III shows dual anti-tumour action by reducing angiogenesis and exerting anti-metastatic effect on lung cancer cells, thus it has the potential to be used as an anti-cancer agent against lung carcinoma.

Keywords: angiogenesis, anti-cancer, marine drugs, matrix metalloproteinases

Procedia PDF Downloads 231

Authors: Wan-Ting Shen, Ching-Liang Hsieh, Yi-Wen Lin

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Electroacupuncture (EA) has been reported effective for many kinds of pain and is a common treatment for acute or chronic pain. However, to date, there are limited studies examining the effect of acupuncture dosage. In our experiment, after injecting mice with Complete Freund’s Adjuvant (CFA) to induce inflammatory pain, two groups of mice were administered two different 15 min EA treatments at 2Hz. The first group received EA at a single acupuncture point (ST36, Zusanli) in both legs (two points), whereas the second group received two acupuncture points in both legs (four points) and the analgesic effect was compared. It was found that double points (ST36, Zusanli and SP6, Sanyinjiao) were significantly superior to single points (ST36, Zusanli) when evaluated using the electronic von Frey Test (mechanic) and Hargreaves’ Test (thermal). Through this study, it is expected more novel physiological mechanisms of acupuncture analgesia will be discovered.

Keywords: anti-inflammation, dose effect, electroacupuncture, pain control

Procedia PDF Downloads 171

Authors: Olushola Ayanda, Simphiwe Nelana, Eliazer Naidoo

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In the present study, the kinetics, equilibrium and thermodynamics of the adsorption of As(III) ions from aqueous solution onto fly ash (FA) was investigated in batch adsorption system. Prior to the adsorption studies, the FA was characterized by means of x-ray fluorescence (XRF), x-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Brunauer-Emmett-Teller (BET) surface area determination. The effect of contact time, initial As(III) concentration, FA dosage, stirring speed, solution pH and temperature was examined on the adsorption rate. Experimental results showed a very good compliance with the pseudo-second-order equation, while the equilibrium study showed that the sorption of As(III) ions onto FA fitted the Langmuir and Freundlich isotherms. The adsorption process is endothermic and spontaneous, moreover, the maximum percentage removal of As(III) achieved with approx. 2.5 g FA mixed with 25 mL of 100 mg/L As(III) solution was 65.4 % at pH 10, 60 min contact time, temperature of 353 K and a stirring speed of 120 rpm.

Keywords: arsenic, fly ash, kinetics, isotherm, thermodynamics

Procedia PDF Downloads 241