Search results for: liver toxicity

Authors: Tanu Sharma, Bikramjit Singh Bajwa, Inderpreet Kaur

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Monitoring of groundwater in Tarn-Taran, Bathinda, Faridkot and Mansa districts of Punjab state, India is essential where this freshwater resource is being over-exploited causing quality deterioration, groundwater depletion and posing serious threats to residents. The present integrated study was done to appraise quality and suitability of groundwater for drinking/irrigation purposes, hydro-geochemical characteristics, source identification and associated health risks. In the present study, groundwater of various districts of Punjab state was found to be heavily contaminated with As followed by U, thus posing high cancerous risks to local residents via ingestion, along with minor contamination of Fe, Mn, Pb and F−. Most health concerns in the study region were due to the elevated concentrations of arsenic in groundwater with average values of 130 µg L-1, 176 µg L-1, 272 µg L-1 and 651 µg L-1 in Tarn-Taran, Bathinda, Faridkot and Mansa districts, respectively, which is quite high as compared to the safe limit as recommended by BIS i.e. 10 µg L-1. In Tarn-Taran, Bathinda, Faridkot and Mansa districts, average uranium contents were found to be 37 µg L-1, 88 µg L-1, 61 µg L-1 and 104 µg L-1, with 51 %, 74 %, 61 % and 71 % samples, respectively, being above the WHO limit of 30 µg L-1 in groundwater. Further, the quality indices showed that groundwater of study region is suited for irrigation but not appropriate for drinking purposes. Hydro-geochemical studies revealed that most of the collected groundwater samples belonged to Ca2+ - Mg2+ - HCO3- type showing dominance of MgCO3 type which indicates the presence of temporary hardness in groundwater. Rock-water reactions and reverse ion exchange were the predominant factors for controlling hydro-geochemistry in the study region. Dissolution of silicate minerals caused the dominance of Na+ ions in the aquifers of study region. Multivariate statistics revealed that along with geogenic sources, contribution of anthropogenic activities such as injudicious application of agrochemicals and domestic waste discharge was also very significant. The results obtained abolished the myth that uranium is only root cause for large number of cancer patients in study region as arsenic and mercury were also present in groundwater at levels that were of health concern to groundwater.

Keywords: uranium, trace elements, multivariate data analysis, risk assessment

Procedia PDF Downloads 53

Authors: Diana Islam, Juan Fang, Vito Fanelli, Bing Han, Julie Khang, Jianfeng Wu, Arthur S. Slutsky, Haibo Zhang

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Introduction: MSC delivery in preclinical models of ARDS has demonstrated significant improvements in lung function and recovery from acute injury. However, the role of MSC delivery in ARDS associated pulmonary fibrosis is not well understood. Some animal studies using bleomycin, asbestos, and silica-induced pulmonary fibrosis show that MSC delivery can suppress fibrosis. While other animal studies using radiation induced pulmonary fibrosis, liver, and kidney fibrosis models show that MSC delivery can contribute to fibrosis. Hypothesis: The beneficial and deleterious effects of MSC in ARDS are modulated by the lung microenvironment at the time of MSC delivery. Methods: To induce ARDS a two-hit mouse model of Hydrochloric acid (HCl) aspiration (day 0) and mechanical ventilation (MV) (day 2) was used. HCl and injurious MV generated fibrosis within 14-28 days. 0.5x106 mouse MSCs were delivered (via both intratracheal and intravenous routes) either in the active inflammatory phase (day 2) or during the remodeling phase (day 14) of ARDS (mouse fibroblasts or PBS used as a control). Lung injury accessed using inflammation score and elastance measurement. Pulmonary fibrosis was accessed using histological score, tissue collagen level, and collagen expression. In addition alveolar epithelial (E) and mesenchymal (M) marker expression profile was also measured. All measurements were taken at day 2, 14, and 28. Results: MSC delivery 2 days after HCl exacerbated lung injury and fibrosis compared to HCl alone, while the day 14 delivery showed protective effects. However in the absence of HCl, MSC significantly reduced the injurious MV-induced fibrosis. HCl injury suppressed E markers and up-regulated M markers. MSC delivery 2 days after HCl further amplified M marker expression, indicating their role in myofibroblast proliferation/activation. While with 14-day delivery E marker up-regulation was observed indicating their role in epithelial restoration. Conclusions: Early MSC delivery can be protective of injurious MV. Late MSC delivery during repair phase may also aid in recovery. However, early MSC delivery during the exudative inflammatory phase of HCl-induced ARDS can result in pro-fibrotic profiles. It is critical to understand the interaction between MSC and the lung microenvironment before MSC-based therapies are utilized for ARDS.

Keywords: acute respiratory distress syndrome (ARDS), mesenchymal stem cells (MSC), hydrochloric acid (HCl), mechanical ventilation (MV)

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Authors: H. Li, L. Ji, J. Su

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Forward osmosis is an emerging technology for separation and has great potential in the concentration of liquid products such as protein, pharmaceutical, and natural products. In pharmacy industry, one of the very tough talks is to concentrate the product in a gentle way since some of the key components may lose bioactivity when exposed to heating or pressurization. Therefore, forward osmosis (FO), which uses inherently existed osmosis pressure instead of externally applied hydraulic pressure, is attractive for pharmaceutical enrichments in a much efficient and energy-saving way. Recently, coordination complexes have been explored as the new class of draw solutes in FO processes due to their bulky configuration and excellent performance in terms of high water flux and low reverse solute flux. Among these coordination complexes, ferric citrate complex with lots of hydrophilic groups and ionic species which make them good solubility and high osmotic pressure in aqueous solution, as well as its low toxicity, has received much attention. However, the chemistry of ferric complexation by citrate is complicated, and disagreement prevails in the literature, especially for the structure of the ferric citrate. In this study, we investigated the chemical reaction with various molar ratio of iron and citrate. It was observed that the ferric citrate complex (Fe-CA2) with molar ratio of 1:1 for iron and citrate formed at the beginning of the reaction, then Fecit would convert to ferric citrate complex at the molar ratio of 1:2 with the proper excess of citrate in the base solution. The structures of the ferric citrate complexes synthesized were systematically characterized by X-ray diffraction (XRD), UV-vis spectroscopy, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR) and Thermogravimetric analysis (TGA). Fe-CA2 solutions exhibit osmotic pressures more than twice of that for NaCl solutions at the same concentrations. Higher osmotic pressure means higher driving force, and this is preferable for the FO process. Fe-CA2 and NaCl draw solutions were prepared with the same osmotic pressure and used in FO process for BSA protein concentration. Within 180 min, BSA concentration was enriched from 0.2 to 0.27 L using Fe-CA draw solutions. However, it was only increased from 0.20 to 0.22 g/L using NaCl draw solutions. A reverse flux of 11 g/m²h was observed for NaCl draw solutes while it was only 0.1 g/m²h for Fe-CA2 draw solutes. It is safe to conclude that Fe-CA2 is much better than NaCl as draw solute and it is suitable for the enrichment of liquid product.

Keywords: draw solutes, ferric citrate complex, forward osmosis, protein enrichment

Procedia PDF Downloads 128

Authors: M. Younus, Muhammad Shafique, M. Athar Khan, Tanveer Akhtar , M. Moeen Athar

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A total of 48 apparently healthy weaned sheep lambs (Ovis aries) of 8-10 weeks old weighing 7-10 Kg were purchased from the contractors, maintained in the experimental station of University of the Punjab, Quaid-e-Azam Campus at Lahore, Pakistan. They were dewormed against nematodes with levamisole (ICI) at recommended dose rates. The feces were tested against the parasitic eggs, no helminths ova were seen. All the 48 sheep lambs were divided into two groups i.e. group A & group B. Group 'A' comprising of 40 sheep, kept as infected groups whereas group 'B' comprising of 08 sheep & kept as a new infected control group. Each sheep lamb of group A was given 3-4 fresh gravid segments contains 2-3 thousand eggs of Echinococcus granulosus. These were collected from experimentally infected dogs by feeding fresh hydrated cysts collected from liver & lungs of sheep after slaughtering. Each lamb was fed with fresh gravid segments for a total period of 5 days or each alternate day. Coagulated blood was collected before the start of infected diet and after every month by jugular phlebotomy of each sheep lamb from the infected & new infected control group. One lamb each from group A & group B was slaughtered at the end of each month for the presence of macroscopic hydatid cyst in viscera & abdominal cavity. After 180 days of the experiment, hydatid cysts were confirmed in the abdominal cavity. Hematological parameters of zero days & then at the end of every month revealed that there was a gradual increase (PL 0.05) in the White Blood Cell (WBC), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin Concentration (MCHC) and Erythrocyte Sedimentation Rates (ESR). The increasing trend was probably due to inflammatory response and lytic effect of the newly developing E. granulosus hydatid cysts. The red blood cell (RBC), Hemoglobin (HB), Packed Cell Volume (PCV) and Mean Corpuscular Hemoglobin (MCH) infected groups were decreased significantly as compared to the control group (PL 0.05). The experiment was terminated at the end of the 7th month. It can be concluded that Echinococcus granulosus can damage livestock and other intermediate hosts such as horses, the development of hydatid cysts affect the organs due to the growing cysts pressuring the organ tissues. Parts of the tissue die, which impairs the functioning of the affected organ. The clinical signs depend on the affected organ. The major damage for livestock is organ condemnation at slaughter.

Keywords: echinococcus granulosus, hydatidosis, sheep, hematology

Procedia PDF Downloads 392

Authors: Amlan Kumar Das, Avinash Marwal, Vikram Pareek

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Liposome plays an important role in medical and pharmaceutical science as e.g. nano scale drug carriers. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment. Magnet-driven liposome used for the targeted delivery of drugs to organs and tissues1. These liposome preparations contain encapsulated drug components and finely dispersed magnetic particles. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment that are generated in vitro. These are useful in terms of biocompatibility, biodegradability, and low toxicity, and can control biodistribution by changing the size, lipid composition, and physical characteristics2. Furthermore, liposomes can entrap both hydrophobic and hydrophilic drugs and are able to continuously release the entrapped substrate, thus being useful drug carriers. Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magneticor paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI)3. The biological synthesis of nanoparticles using plant extracts plays an important role in the field of nanotechnology4. Green-synthesized magnetite nanoparticles-protein hybrid has been produced by treating Iron (III)/Iron(II) chloride with the leaf extract of Dhatura Inoxia. The phytochemicals present in the leaf extracts act as a reducing as well stabilizing agents preventing agglomeration, which include flavonoids, phenolic compounds, cardiac glycosides, proteins and sugars. The magnetite nanoparticles-protein hybrid has been trapped inside the aqueous core of the liposome prepared by reversed phase evaporation (REV) method using oleic and linoleic acid which has been shown to be driven under magnetic field confirming the formation magnetic liposome (ML). Chemical characterization of stealth magnetic liposome has been performed by breaking the liposome and release of magnetic nanoparticles. The presence iron has been confirmed by colour complex formation with KSCN and UV-Vis study using spectrophotometer Cary 60, Agilent. This magnet driven liposome using nanoparticles-protein hybrid can be a smart vesicles for the targeted drug delivery.

Keywords: nanoparticles-protein hybrid, magnetic liposome, medical, pharmaceutical science

Procedia PDF Downloads 229

Authors: Zahra Shokrolahi, Mohammad Reza Atashzar

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The goals of treating patients with breast cancer are to cure the disease, prolong survival, and improve quality of life. Immune cells in the tumor microenvironment have an important role in regulating tumor progression. The term of cellular immunotherapy refers to the administration of living cells to a patient; this type of immunotherapy can be active, such as a dendritic cell (DC) vaccine, in that the cells can stimulate an anti-tumour response in the patient, or the therapy can be passive, whereby the cells have intrinsic anti-tumour activity; this is known as adoptive cell transfer (ACT) and includes the use of autologous or allogeneic lymphocytes that may, or may not, be modified. The most important breast cancer cellular immunotherapies involving the use of T cells and natural killer (NK) cells in adoptive cell transfer, as well as dendritic cells vaccines. T cell-based therapies including tumour-infiltrating lymphocytes (TILs), engineered TCR-T cells, chimeric antigen receptor (CAR T cell), Gamma-delta (γδ) T cells, natural killer T (NKT) cells. NK cell-based therapies including lymphokine-activated killers (LAK), cytokine-induced killer (CIK) cells, CAR-NK cells. Adoptive cell therapy has some advantages and disadvantages some. TILs cell strictly directed against tumor-specific antigens but are inactive against tumor changes due to immunoediting. CIK cell have MHC-independent cytotoxic effect and also need concurrent high dose IL-2 administration. CAR T cell are MHC-independent; overcome tumor MHC molecule downregulation; potent in recognizing any cell surface antigen (protein, carbohydrate or glycolipid); applicable to a broad range of patients and T cell populations; production of large numbers of tumor-specific cells in a moderately short period of time. Meanwhile CAR T cells capable of targeting only cell surface antigens; lethal toxicity due to cytokine storm reported. Here we present the most popular cancer cellular immunotherapy approaches and discuss their clinical relevance referring to data acquired from clinical trials .To date, clinical experience and efficacy suggest that combining more than one immunotherapy interventions, in conjunction with other treatment options like chemotherapy, radiotherapy and targeted or epigenetic therapy, should guide the way to cancer cure.

Keywords: breast cancer , cell therapy , CAR T cell , CIK cells

Procedia PDF Downloads 104

Authors: Tzu-Ting Hu, Jung-Der Wang, Ming-Yeng Lin, Jin-Luh Chen, Perng-Jy Tsai

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The vinyl chloride monomer (VCM) has been classified as group 1 (human) carcinogen by the IARC. Workers exposed to VCM are known associated with the development of the liver cancer and hence might cause economical and health losses. Particularly, for those work for the petrochemical industry have been seriously concerned in the environmental and occupational health field. Considering assessing workers’ health risks and their resultant economical and health losses requires the establishment of long-term VCM exposure data for any similar exposure group (SEG) of interest, the development of suitable technologies has become an urgent and important issue. In the present study, VCM exposures for petrochemical industry workers were determined firstly based on the database of the 'Workplace Environmental Monitoring Information Systems (WEMIS)' provided by Taiwan OSHA. Considering the existence of miss data, the reconstruction of historical exposure techniques were then used for completing the long-term exposure data for SEGs with routine operations. For SEGs with non-routine operations, exposure modeling techniques, together with their time/activity records, were adopted for determining their long-term exposure concentrations. The Bayesian decision analysis (BDA) was adopted for conducting exposure and health risk assessments for any given SEG in the petrochemical industry. The resultant excessive cancer risk was then used to determine the corresponding loss of quality-adjusted life expectancy (QALE). Results show that low average concentrations can be found for SEGs with routine operations (e.g., VCM rectification 0.0973 ppm, polymerization 0.306 ppm, reaction tank 0.33 ppm, VCM recovery 1.4 ppm, control room 0.14 ppm, VCM storage tanks 0.095 ppm and wastewater treatment 0.390 ppm), and the above values were much lower than that of the permissible exposure limit (PEL; 3 ppm) of VCM promulgated in Taiwan. For non-routine workers, though their high exposure concentrations, their low exposure time and frequencies result in low corresponding health risks. Through the consideration of exposure assessment results, health risk assessment results, and QALE results simultaneously, it is concluded that the proposed method was useful for prioritizing SEGs for conducting exposure abatement measurements. Particularly, the obtained QALE results further indicate the importance of reducing workers’ VCM exposures, though their exposures were low as in comparison with the PEL and the acceptable health risk.

Keywords: exposure assessment, health risk assessment, petrochemical industry, quality-adjusted life years, vinyl chloride monomer

Procedia PDF Downloads 169

Authors: Shwu-Ling Peng, Chiung-Man Tsai, Chia-Jui Weng

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Chronic micro-inflammation is a hallmark of many aging-related neurodegenerative and metabolic syndrome-driven diseases. In high glucose (HG) environment, reactive oxygen species (ROS) is generated and the ROS induced inflammation, cytokines secretion, DNA damage, and cell cycle arrest to lead to cellular senescence. Water chestnut shell (WCS) is a plant hull which containing polyphenolic compounds and showed antioxidant and anticancer activities. Orchid, which containing a natural polysaccharide compound, possesses many physiological activities including anti-inflammatory and neuroprotective effects. These agricultural plants might be able to reduce oxidative stress and inflammation. This study was used HG-induced human normal dermal fibroblasts (HG-HNDFs) as an in vitro model to disclose the effects of water extract of Phalaenopsis orchid flower (WEPF) and ethanol extract of water chestnut shell (EEWCS) on the anti-aging and their underlying molecular mechanisms. The toxicity of extracts on human normal dermal fibroblasts (HNDFs) was determined by MTT method. The senescence of cells was assayed by β-galactosidase (SA-β-gal) kit. ROS and nitrate production was analyzed by Intracellular ROS contents and ELISA, respectively. Western blotting was used to detect the proteins in cells. The results showed that the exposure of HNDFs to HG (30 mM) for 72 h were caused cellular senescence and arrested cells at G0/G1 phase. Indeed, the treatment of HG-HNDFs with WEPF (200 μg/ml) and EEWCS (10 μg/ml) significantly released cell cycle arrest and promoted cell proliferation. The G1/S phase transition regulatory proteins such as protein retinoblastoma (pRb), p53, and p16ᴵᴺᴷ⁴ᵃ depressed by WEPF and EEWCS were also observed. Additionally, the treatment of WEPF and EEWCS increased the activity of HO-1 through upregulating Nrf2 as well as decreased the ROS and NO of HG-HNDFs. Therefore, the senescence marker protein-30 (SMP30) in cells was diminished. In conclusion, the WEPF and EEWCS might inhibit HG-induced aging of HNDFs by reducing oxidative stress and free radicals.

Keywords: agricultural plant extract, anti-aging, high glucose, Phalaenopsis orchid flower, water chestnut shell

Procedia PDF Downloads 129

Authors: Matheus Madureira Matos, Alexandre Rodrigues Farias

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Magnetic Resonance Imaging (MRI) is a vital imaging technique used in both clinical and pre-clinical areas to obtain detailed anatomical and functional information. However, MRI scans can be expensive, time-consuming, and often require the use of anesthetics to keep animals still during the imaging process. Anesthetics are commonly administered to animals undergoing MRI scans to ensure they remain still during the imaging process. However, prolonged or repeated exposure to anesthetics can have adverse effects on animals, including physiological alterations and potential toxicity. Minimizing the duration and frequency of anesthesia is, therefore, crucial for the well-being of research animals. In recent years, various sampling trajectories have been investigated to reduce the number of MRI measurements leading to shorter scanning time and minimizing the duration of animal exposure to the effects of anesthetics. Compressed sensing (CS) and sampling trajectories, such as cartesian, spiral, and radial, have emerged as powerful tools to reduce MRI data while preserving diagnostic quality. This work aims to apply CS and cartesian, spiral, and radial sampling trajectories for the reconstruction of MRI of the abdomen of mice sub-sampled at levels below that defined by the Nyquist theorem. The methodology of this work consists of using a fully sampled reference MRI of a female model C57B1/6 mouse acquired experimentally in a 4.7 Tesla MRI scanner for small animals using Spin Echo pulse sequences. The image is down-sampled by cartesian, radial, and spiral sampling paths and then reconstructed by CS. The quality of the reconstructed images is objectively assessed by three quality assessment techniques RMSE (Root mean square error), PSNR (Peak to Signal Noise Ratio), and SSIM (Structural similarity index measure). The utilization of optimized sampling trajectories and CS technique has demonstrated the potential for a significant reduction of up to 70% of image data acquisition. This result translates into shorter scan times, minimizing the duration and frequency of anesthesia administration and reducing the potential risks associated with it.

Keywords: compressed sensing, magnetic resonance, sampling trajectories, small animals

Procedia PDF Downloads 44

Authors: Omoruyi G. Idemudia, Alexander P. Sadimenko

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The need for the development of new sustainable bioactive compounds with unique properties that can become potential replacement for commonly used medicinal drugs has continued to gain tremendous research concerns because of the problems of disease resistant to these medicinal drugs and their toxicity effects. NOS-donor heterocycles are particularly of interest as they have showed good pharmacological activities in the midst of their interesting chelating properties towards metal ions, an important characteristic for transition metal based drugs design. These new compounds have also gained application as dye sensitizers in solar cell panels for the generation of renewable solar energy, as greener water purification polymer for supply and management of clean water and as catalysts which are used to reduce the amount of pollutants from industrial reaction processes amongst others, because of their versatile properties. Di-ketone acylpyrazolones and their azomethine schiff bases have been employed as pharmaceuticals as well as analytical reagents, and their application as transition metal complexes have being well established. In this research work, a new 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one-thiosemicarbazone was synthesized from the reaction of 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one and thiosemicarbazide in methanol. The pure isolate of the thiosemicarbazone was further reacted with aqueous solutions of palladium and platinum salts to obtain their metal complexes, in an effort towards the discovery of transition metal based synthetic drugs. These compounds were characterized by means of analytical, spectroscopic, thermogravimetric analysis TGA, as well as x-ray crystallography. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one thiosemicarbazone crystallizes in a triclinic crystal system with a P-1 (No. 2) space group according to x-ray crystallography. The tridentate NOS ligand formed a tetrahedral geometry on coordinating with metal ions. Reported compounds showed varying antioxidant free radical scavenging activities against 2, 2-diphenyl-1-picrylhydrazyl DPPH radical at 100, 200, 300, 400 and 500 µg/ml concentrations. The platinum complex have shown a very good antioxidant property against DPPH with an IC50 of 76.03 µg/ml compared with standard ascorbic acid (IC50 of 74.66 µg/ml) and as such have been identified as a potential anticancer candidate.

Keywords: acylpyrazolone, free radical scavenging activities, tridentate ligand, x-ray crystallography

Procedia PDF Downloads 162

Authors: Emma R. Arakelova, Stepan G. Grigoryan, Flora G. Arsenyan, Nelli S. Babayan, Ruzanna M. Grigoryan, Natalia K. Sarkisyan

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Novel nanosize zinc oxide composites of doxorubicin obtained by deposition of 180 nm thick zinc oxide film on the drug surface using DC-magnetron sputtering of a zinc target in the form of gels (PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO) were studied for drug delivery applications. The cancer specificity was revealed both in in vitro and in vivo models. The cytotoxicity of the test compounds was analyzed against human cancer (HeLa) and normal (MRC5) cell lines using MTT colorimetric cell viability assay. IC50 values were determined and compared to reveal the cancer specificity of the test samples. The mechanistic study of the most active compound was investigated using Flow cytometry analyzing of the DNA content after PI (propidium iodide) staining. Data were analyzed with Tree Star FlowJo software using cell cycle analysis Dean-Jett-Fox module. The in vivo anticancer activity estimation experiments were carried out on mice with inoculated ascitic Ehrlich’s carcinoma at intraperitoneal introduction of doxorubicin and its zinc oxide compositions. It was shown that the nanosize zinc oxide film deposition on the drug surface leads to the selective anticancer activity of composites at the cellular level with the range of selectivity index (SI) from 4 (Starch+NaCMC+Dox+ZnO) to 200 (PEO(gel)+Dox+ZnO) which is higher than that of free Dox (SI = 56). The significant increase in vivo antitumor activity (by a factor of 2-2.5) and decrease of general toxicity of zinc oxide compositions of doxorubicin in the form of the above mentioned gels compared to free doxorubicin were shown on the model of inoculated Ehrlich's ascitic carcinoma. Mechanistic studies of anticancer activity revealed the cytostatic effect based on the high level of DNA biosynthesis inhibition at considerable low concentrations of zinc oxide compositions of doxorubicin. The results of studies in vitro and in vivo behavior of PEO+Dox+ZnO and Starch+NaCMC+Dox+ZnO composites confirm the high potential of the nanosize zinc oxide composites as a vector delivery system for future application in cancer chemotherapy.

Keywords: anticancer activity, cancer specificity, doxorubicin, zinc oxide

Procedia PDF Downloads 384

Authors: A. H. Taghdisi, M. Mirmohammadi, S. Kamali

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Evening primrose (Oenothera biennis L.) is a biennial and herbaceous and one of the most important species of medicinal plants in the world. due to the production of unsaturated fatty acids such as linoleic acid, alpha-linolenic acid, etc. in its seeds and roots, and compounds such as kaempferol in its leaves, Evening primrose has important medicinal efficiency such as reducing premenstrual problems, acceleration of wound healing, inhibiting platelet aggregation, sedation of cardiovascular diseases, and treatment of viral infections. The sap of the plant is used to treat warts, and the plant itself is used as a charm against mental and spiritual diseases and poisonous animals. Its leaves have significant antibacterial activity against yellow staphylococci. It is also used in the treatment of poisoning, especially the toxication caused by the consumption of alcoholic beverages, in the treatment of arteriosclerosis and diseases caused by liver cell insufficiency. Low germination and production speed are the problems of evening primrose growth and propagation. In the present study, extracts were obtained from four components (flowers, stems, seeds, leaves) of the evening primrose plant using the Soxhlet apparatus. To measure the antibacterial properties against MDR bacteria, microbial methods, including dilution, cultivation on a plate containing nutrient agar culture medium, and disc diffusion in agar, were performed using Staphylococcus aureus and Escherichia coli bacteria on all four extracts. The maximum antibacterial activity related to the dilution method was obtained in all extracts. In the plate culture method, antibacterial activity was obtained for all extracts in the nutrient agar medium. The maximum diameter of the non-growth halo was obtained in the disc diffusion method in agar in the leaf extract. The statistical analysis of the microbial part was done by one-way ANOVA test (SPSS). By comparing the amount of omega-3 in extracts of Iranian and foreign oils available in the market and the extracts extracted from evening primrose plant samples with gas chromatography, it is shown that the stem extract had the most omega-3 (oleic acid) and compared to the extract of the mentioned oils, it had the highest amount of omega-3 overall. Also, the amount of omega-3 in the extract of Iranian oils was much higher than in the extract of foreign oils. It should be noted that the extract of foreign oils had a more complete composition of omega-3 than the extract of Iranian oils.

Keywords: antibacterial activity, MDR bacteria, evening primrose, omega-3

Procedia PDF Downloads 68

Authors: Satya P. Dubey, Hrushikesh A Abhyankar, Veronica Marchante, James L. Brighton, Björn Bergmann

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Aims: To develop a mathematical model that simulates the ROP of PLA taking into account the effect of alternative energy to be implemented in a continuous reactive extrusion production process of PLA. Introduction: The production of large amount of waste is one of the major challenges at the present time, and polymers represent 70% of global waste. PLA has emerged as a promising polymer as it is compostable, biodegradable thermoplastic polymer made from renewable sources. However, the main limitation for the application of PLA is the traces of toxic metal catalyst in the final product. Thus, a safe and efficient production process needs to be developed to avoid the potential hazards and toxicity. It has been found that alternative energy sources (LASER, ultrasounds, microwaves) could be a prominent option to facilitate the ROP of PLA via continuous reactive extrusion. This process may result in complete extraction of the metal catalysts and facilitate less active organic catalysts. Methodology: Initial investigation were performed using the data available in literature for the reaction mechanism of ROP of PLA based on conventional metal catalyst stannous octoate. A mathematical model has been developed by considering significant parameters such as different initial concentration ratio of catalyst, co-catalyst and impurity. Effects of temperature variation and alternative energies have been implemented in the model. Results: The validation of the mathematical model has been made by using data from literature as well as actual experiments. Validation of the model including alternative energies is in progress based on experimental data for partners of the InnoREX project consortium. Conclusion: The model developed reproduces accurately the polymerisation reaction when applying alternative energy. Alternative energies have a great positive effect to increase the conversion and molecular weight of the PLA. This model could be very useful tool to complement Ludovic® software to predict the large scale production process when using reactive extrusion.

Keywords: polymer, poly-lactic acid (PLA), ring opening polymerization (ROP), metal-catalyst, bio-degradable, renewable source, alternative energy (AE)

Procedia PDF Downloads 339

Authors: Simona Dostalova, Dita Munzova, Ana Maria Jimenez Jimenez, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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The boom of nanomedicine in recent years has led to the development of numerous new nanomaterials that can be used as nanocarriers in the drug delivery. These nanocarriers can either be synthetic or natural-based. The disadvantage of many synthetic nanocarriers is their toxicity in patient’s body. Protein cages that can naturally be found in human body do not exhibit such disadvantage. However, the release of cargo from some protein cages in target cells can be problematic. As a special type of protein cages can serve the capsid of many viruses, including phage. Phages infect bacterial cells; therefore they are not harmful to human cells. The targeting of phage particles to cancer cells can be solved by producing of empty phage capsids during which the targeting moieties (e.g. peptides) can be cloned into genes of phage capsid to decorate its surface. Moreover, the produced capsids do not contain viral nucleic acid and are therefore not infectious to beneficial bacteria in the patient’s body. The protein cage composed of viral capsid is larger than other frequently used apoferritin cage but its size is still small enough to benefit from passive targeting by Enhanced Permeability and Retention effect. In this work, bacteriophage λ was used, both whole and its empty capsid for delivery of different cytotoxic drugs (cisplatin, carboplatin, oxaliplatin, etoposide and doxorubicin). Large quantities of phage λ were obtained from phage λ-producing strain of E. coli cultivated in medium with 0.2 % maltose. After killing of E. coli with chloroform and its removal by centrifugation, the phage was concentrated by ultracentrifugation at 130 000 g and 4 °C for 3 h. The encapsulation of the drugs was performed by infusion method and four different concentrations of the drugs were encapsulated (200; 100; 50; 25 µg/ml). Free molecules of drugs were removed by dialysis. The encapsulation was verified using spectrophotometric and electrochemical methods. The amount of encapsulated drug linearly increased with the amount of applied drug (determination coefficient R2=0.8013). 76% of applied drug was encapsulated in phage λ particles (concentration of 10 µg/ml), even with the highest applied concentration of drugs, 200 µg/ml. Only 1% of encapsulated drug was detected in phage DNA. Similar results were obtained with encapsulation in phage empty capsid. Therefore, it can be concluded that the encapsulation of drugs into phage particles is efficient and mostly occurs by interaction of drugs with protein capsid.

Keywords: cytostatics, drug delivery, nanocarriers, phage capsid

Procedia PDF Downloads 466

Authors: Luís R. Silva, Ana C. Gonçalves, Catarina Bento, Fábio Jesus, Branca M. Silva

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Prunus avium Linnaeus, more known as sweet cherry, is one of the most appreciated fruit worldwide. Most of these quantities are produced in Fundão region, being Saco the cultivar most produced. Saco is very rich in bioactive compounds, especially phenolics, and presents great antioxidant capacity. The purpose of the present study was to investigate the chemical profile and biological potential, concerning antioxidant, anti-diabetic activity and protective effects towards erythrocytes by Saco sweet cherry collected from Fundão region (Portugal). The hydroethanolic extracts were prepared and passed through a C18 solid-phase extraction column. The phenolic profile analyzed by LC-DAD method allowed to the identification of 22 phenolic compounds, being 16 non-phenolics and 6 anthocyanins. In respect to non-coloured phenolics, 3-O-caffeoylquinic and ρ-coumaroylquinic acids were the main ones. Concerning to anthocyanins, cyanidin-3-O-rutinoside was found in higher amounts. Relatively to biological potential, Saco showed great antioxidant potential, through DPPH and NO radical assays, with IC50 =16.24 ± 0.46 µg/mL and IC50 = 176.69 ± 3.35 µg/mL for DPPH and NO, respectively. These results were similar to those obtained for ascorbic acid control (IC50 = 16.92 ± 0.69 and IC50 = 162.66 ± 1.31 μg/mL for DPPH and NO, respectively). In respect to antidiabetic potential, Saco revealed capacity to inhibit α-glucosidase in a dose-dependent manner (IC50 = 10.79 ± 0.40 µg/mL), being much active than positive control acarbose (IC50 = 306.66 ± 0.84 μg/mL). Additionally, Saco extracts revealed protective effects against ROO•-mediated toxicity generated by AAPH in human blood erythrocytes, inhibiting hemoglobin oxidation (IC50 = 38.57 ± 0.96 μg/mL) and hemolysis (IC50 = 73.03 ± 1.48 μg/mL), in a concentration-dependent manner. However, Saco extracts were less effective than quercetin control (IC50 = 3.10 μg/mL and IC50 = 0.7 μg/mL for inhibition of hemoglobin oxidation and hemolysis, respectively). The results obtained showed that Saco is an excellent source of phenolic compounds. These ones are natural antioxidant substances, which easily capture reactive species. This work presents new insights regarding sweet cherry antioxidant properties which may be useful for the future development of new therapeutic strategies for preventing or attenuating oxidative-related disorders.

Keywords: antioxidant capacity, health benefits, phenolic compounds, saco

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Authors: Masome Moeni, Roya Abedizadeh, Elham Aram, Hamid Sadeghi-Abandansari, Davood Sabour, Robert Menzel, Ali Hassanpour

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Significant number of studies and preclinical research in formulation of cancer nano-pharmaceutics have led to an improvement in cancer care. Nonetheless, the antineoplastic agents have ‘failed to live up to its promise’ since their clinical performance is moderately low. For almost ninety years, iron oxide nanoparticles (IONPS) have managed to keep its reputation in clinical application due to their low toxicity, versatility and multi-modal capabilities. Drug Administration approved utilization of IONPs for diagnosis of cancer as contrast media in magnetic resonance imaging, as heat mediator in magnetic hyperthermia and for the treatment of iron deficiency. Furthermore, IONPs have high drug-loading capacity, which makes them good candidates as therapeutic agent transporters. There are yet challenges to overcome for successful clinical application of IONPs, including stability of drug and poor delivery, which might lead to (i) drug resistance, (ii) shorter blood circulation time, and (iii) rapid elimination and adverse side effects from the system. In this study, highly stable and super paramagnetic IONPs were prepared for efficient and targeted drug delivery in cancer treatment. The synthesis procedure was briefly involved the production of IONPs via co-precipitation followed by coating with tetraethyl orthosilicate and 3-aminopropylethoxysilane and grafting with folic acid for stability targeted purposes and controlled drug release. Physiochemical and morphological properties of modified IONPs were characterised using different analytical techniques. The resultant IONPs exhibited clusters of 10 nm spherical shape crystals with less than 100 nm size suitable for drug delivery. The functionalized IONP showed mesoporous features, high stability, dispersibility and crystallinity. Subsequently, the functionalized IONPs were successfully loaded with oxaliplatin, a chemotherapeutic agent, for a controlled drug release in an actively targeting cancer cells. FT-IR observations confirmed presence of oxaliplatin functional groups, while ICP-MS results verified the drug loading was ~ 1.3%.

Keywords: cancer treatment, chemotherapeutic agent, drug delivery, iron oxide, multi-functional nanoparticle

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Authors: Nelson R. Osungbemiro, O. A. Bello-Olusoji, M. Oladipupo

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This study was carried out to determine the effects of probiotics Pseudomonas fluorescens on the growth performance, histology examination and immune modulation of African Catfish, (Clarias gariepinus) challenged with Clostridium botulinum. P. fluorescens, and C. botulinum isolates were removed from the gut, gill and skin organs of procured adult samples of Clarias gariepinus from commercial fish farms in Akure, Ondo State, Nigeria. The physical and biochemical tests were performed on the bacterial isolates using standard microbiological techniques for their identification. Antibacterial activity tests on P. fluorescens showed inhibition zone with mean value of 3.7 mm which indicates high level of antagonism. The experimental diets were prepared at different probiotics bacterial concentration comprises of five treatments of different bacterial suspension, including the control (T1), T2 (10³), T3 (10⁵), T4 (10⁷) and T5 (10⁹). Three replicates for each treatment type were prepared. Growth performance and nutrients utilization indices were calculated. The proximate analysis of fish carcass and experimental diet was carried out using standard methods. After feeding for 70 days, haematological values and histological test were done following standard methods; also a subgroup from each experimental treatment was challenged by inoculating Intraperitonieally (I/P) with different concentration of pathogenic C. botulinum. Statistically, there were significant differences (P < 0.05) in the growth performance and nutrient utilization of C. gariepinus. Best weight gain and feed conversion ratio were recorded in fish fed T4 (10⁷) and poorest value obtained in the control. Haematological analyses of C. gariepinus fed the experimental diets indicated that all the fish fed diets with P. fluorescens had marked significantly (p < 0.05) higher White Blood Cell than the control diet. The results of the challenge test showed that fish fed the control diet had the highest mortality rate. Histological examination of the gill, intestine, and liver of fish in this study showed several histopathological alterations in fish fed the control diets compared with those fed the P. fluorescens diets. The study indicated that the optimum level of P. fluorescens required for C. gariepinus growth and white blood cells formation is 10⁷ CFU g⁻¹, while carcass protein deposition required 10⁵ CFU g⁻¹ of P. fluorescens concentration. The study also confirmed P. fluorescens as efficient probiotics that is capable of improving the immune response of C. gariepinus against the attack of a virulent fish pathogen, C. botulinum.

Keywords: Clarias gariepinus, Clostridium botulinum, probiotics, Pseudomonas fluorescens

Procedia PDF Downloads 124

Authors: Marco Soto-Arriaza, Eduardo Cena-Ahumada, Jaime Melendez-Rojel

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Background: Liposomes have been widely used as a model of lipid bilayer to study the physicochemical properties of biological membrane, encapsulation, transport and release of different molecules. Furthermore, extensive research has focused on improving the efficiency in the transport of drugs, developing tools that improve the release of the encapsulated drug from liposomes. In this context, the enzymatic activity of PLA₂, despite having been shown to be an effective tool to promote the release of drugs from liposomes, is still an open field of research. Aim: The aim of the present study is to explore the effect of cholesterol (Cho) and amphipathic di- and tri-block copolymers, on calcein release mediated by enzymatic activity of PLA2 in Dipalmitoylphosphatidylcholine (DPPC) liposomes under physiological conditions. Methods: Different dispersions of DPPC, cholesterol, di-block POE₄₅-PCL₅₂ or tri-block PCL₁₂-POE₄₅-PCL₁₂ were prepared by the extrusion method after five freezing/thawing cycles; in Phosphate buffer 10mM pH 7.4 in presence of calcein. DPPC liposomes/Calcein were centrifuged at 15000rpm 10 min to separate free calcein. Enzymatic activity assays of PLA₂ were performed at 37°C using the TBS buffer pH 7.4. The size distribution, polydispersity, Z-potential and Calcein encapsulation of DPPC liposomes was monitored. Results: PLA₂ activity showed a slower kinetic of calcein release up to 20 mol% of cholesterol, evidencing a minimum at 10 mol% and then a maximum at 18 mol%. Regardless of the percentage of cholesterol, up to 18 mol% a one-hundred percentage release of calcein was observed. At higher cholesterol concentrations, PLA₂ showed to be inefficient or not to be involved in calcein release. In assays where copolymers were added in a concentration lower than their cmc, a similar behavior to those showed in the presence of Cho was observed, that is a slower kinetic in calcein release. In both experimental approaches, a one-hundred percentage of calcein release was observed. PLA₂ was shown to be sensitive to the 4-(4-Octadecylphenyl)-4-oxobutenoic acid inhibitor and calcium, reducing the release of calcein to 0%. Cell viability of HeLa cells decreased 7% in the presence of DPPC liposomes after 3 hours of incubation and 17% and 23% at 5 and 15 hours, respectively. Conclusion: Calcein release from DPPC liposomes, mediated by PLA₂ activity, depends on the percentage of cholesterol and the presence of copolymers. Both, cholesterol up to 20 mol% and copolymers below it cmc could be applied to the regulation of the kinetics of antitumoral drugs release without inducing cell toxicity per se.

Keywords: amphipathic copolymers, calcein release, cholesterol, DPPC liposome, phospholipase A₂

Procedia PDF Downloads 133

Authors: Y. Sakai, C. Wang

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The decrease in agricultural production due to soil deterioration has been an urgent task. Soil acidification is a potentially serious land degradation issue and it will have a major impact on agricultural productivity and sustainable farming systems. In China, acid soil is mainly distributed in the southern part, the decrease in agricultural production and heavy metal contamination are serious problems. In addition, not only environmental and health problems due to the exhaust gas such as mainly sulfur dioxide (SO₂) but also the generation of a huge amount of construction and demolition wastes with the accelerating urbanization has emerged as a social problem in China. Therefore, the need for the recycling and reuse of both desulfurization waste and waste concrete is very urgent and necessary. So we have investigated the effectiveness as acid soil amendments of both coal bio-briquette ash and waste concrete. In this paper, acid soil (AS1) in Nanjing (pH=6.0, EC=1.6dSm-1) and acid soil (AS2) in Guangzhou (pH=4.1, EC=0.2dSm-1) were investigated in soil amelioration test. Soil amendments were three coal bio-briquette ashes (BBA1, BBA2 and BBA3), the waste cement fine powders (CFP) ( < 200µm (particle diameter)), waste concrete particles (WCP) ( < 4.75mm ( < 0.6mm, 0.6-1.0mm, 1.0-2.0mm, 2.0-4.75mm)), and six mixtures with two coal bio-briquette ashes (BBA2 and BBA3), CFP, WCP( < 0.6mm) and WCP(2.0-4.75mm). In acid soil amelioration test, the three BBAs, CFP and various WCPs based on exchangeable calcium concentration were added to two acid soils. The application rates were from 0 wt% to 3.5 wt% in AS1 test and from 0 wt% to 6.0 wt% in AS2 test, respectively. Soil chemical properties (pH, EC, exchangeable and soluble ions (Na, Ca, Mg, K)) before and after mixing with soil amendments were measured. In addition, Al toxicity and the balance of salts (CaO, K₂O, MgO) in soil after amelioration was evaluated. The order of pH and exchangeable Ca concentration that is effective for acid soil amelioration was WCP(0.6mm) > CFP > WCP(2.0-4.25mm) > BB1 > BB2 > BB3. In all AS 1 and AS 2 amelioration tests using three BBAs, the pH and EC increased slightly with the increase of application rate and reached to the appropriate value range of both pH and EC in BBA1 only. Because BBA1 was higher value in pH and exchangeable Ca. After that, soil pH and EC with the increase in the application rate of BBA2, BBA3 and by using CFP, WC( < 0.6mm), WC(2.0-4.75mm) as soil amendment reached to each appropriate value range, respectively. In addition, the mixture amendments with BBA2, BBA3 CFP, WC( < 0.6mm), and WC(2.0-4.75mm) could ameliorate at a smaller amount of application rate in case of BBA only. And the exchangeable Al concentration decreased drastically with the increase in pH due to soil amelioration and was under the standard value. Lastly, the heavy metal (Cd, As, Se, Ni, Cr, Pb, Mo, B, Cu, Zn) contents in new soil amendments were under control standard values for agricultural use in China. Thus we could propose a new acid soil amelioration method using coal bio-briquette ash and waste concrete in China.

Keywords: acid soil, coal bio-briquette ash, soil amelioration, waste concrete

Procedia PDF Downloads 160

Authors: E. Isaac, I. Jalo, Y. Alkali, A. Ajani, A. Rasaki, Y. Jibrin, K. Mustapha, A. Ayuba, S. Charanchi, H. Danlami

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Introduction: Hepatitis B infection continues to be a serious global health problem with about 2 billion people infected worldwide, many of these in sub-Saharan Africa. Nigeria is one of the countries with the highest incidence, with a prevalence of 10-15%. Methods: Records of Hepatitis B surface and envelope antigen test results in adults in Federal Teaching Hospital, Gombe between May 2000 and May 2015 were retrieved and analyzed. Findings: Adult out-patient consultations and in-patient admissions were 343,083 and 67,761 respectively, accounting for 87% of total. Hepatitis B surface antigenaemia was tested for in 23,888 adults and children. 88.9% (21240) were adults. Males constituted 56% (11902/21240) and females 44% (9211/21240). 5104 (24.0%) of tested individuals were 19-25years; 12,039 (56.7%) 26-45years; 21119 (9.0%) 46-55years; 2.8% (590/21240) and 766 (3.6%) >65years. Among adult males, 17% (2133/11902) was contributed by ages 19-25. 58% (7017/11902), 11.9% (1421/11902), 6.4% (765/11902) and 4.7% (563/11902) of males were 26-45 years old, 46-55 years old and 56-65 years and >65year old respectively. Adults aged 19-25years, 26-45 years, 46-55years, 56-65 and > 65years each constituted 32% (2966/9211); 54.4% (5009/9211); 7.4% (684/9211), 3.8% (350/9211) and 2.2% (201/9211) of females respectively. 16.2% (3431/21,240) demonstrated Hepatitis B surface antigenaemia. The sero-positivity rate was 16.9% (865//5104) between 19-25years, 21.2% (2559/12,039) among 26-45year old individuals. 17.9% (377/2111); 14.1% (83/590) and 7.3% (56/766) of 46-55year old, 56-65year old and >65year old individuals screened were seropositive. The highest sero-positivity rate was found in male young adults aged 19-25years 27.9% (398/1426) and lowest in elderly males 7.4% (28/377). HBe antigen testing rate among HbSAg seropositive individuals was 97.3% (3338/3431). Males constituted 59.7% (1992/3338) and females 40.3% (1345/3338). 25.3% (844/3338) were aged 19-25years; 61.1% (2039/3338) 26-45years; 10.2% (340/3338) 46-55years; 2.7% (90/3338) 56-65years and 0.7% >65years old. HB e antigenaemia was positive in 8.2% (275/3338) of those tested. 41% (113/275); 50.2% (138/275); 5.4% (15/275); 1.8% (5/275) and 1.1 (3/275) of HB e sero-positivity was among age groups 19-25, 26-45, 46-55, 56-65 and > 65year old individuals. Dual sero-positivity rate was highest 13% (113/844) in young adults 19-25years and lowest between 46-55years; 15/340 (4.4%). 4.2% (15/360); 13.5% (69/512); 6.7% (90/1348); 4.6% (10/214); 5% (2/40) and 6.7% (1/15) of males aged 19-25; 26-45; 46-55; 56-65; and >65years had HB e antigenaemia respectively. Among females - 27/293 (9.2%) aged 19-25; 26/500 (5.2%) 26-45; 2/84 (2.4%) 46-55; 1/12 (8.3%) 56-65 and 1/9(11.1%) >65years had dual antigenaemia. In women of childbearing age, 6.9% (53/793) had a dual carriage. Conclusion: Dual hepatitis B surface and envelope antigenaemia are highest in young adult males. This will have significant implications for the development of chronic liver disease and hepatocellular carcinoma.

Keywords: adult, Hepatitis B, Nigeria, dual carriage

Procedia PDF Downloads 234

Authors: Bruno Baptista, Andreia S. R. Oliveira, Patricia V. Mendonca, Jorge F. J. Coelho, Fani Sousa

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Drug delivery systems are designed to allow adequate protection and controlled delivery of drugs to specific locations. These systems aim to reduce side effects and control the biodistribution profile of drugs, thus improving therapeutic efficacy. This study involved the synthesis of polymeric nanoparticles, based on amphiphilic diblock copolymers, comprising a biocompatible, poly (oligo (ethylene oxide) methyl ether methacrylate (POEOMA) as hydrophilic segment and a pH-sensitive block, the poly (2-diisopropylamino)ethyl methacrylate) (PDPA). The objective of this work was the development of polymeric pH-responsive nanoparticles to encapsulate and carry small RNAs as a model to further develop non-coding RNAs delivery systems with therapeutic value. The responsiveness of PDPA to pH allows the electrostatic interaction of these copolymers with nucleic acids at acidic pH, as a result of the protonation of the tertiary amine groups of this polymer at pH values below its pKa (around 6.2). Initially, the molecular weight parameters and chemical structure of the block copolymers were determined by size exclusion chromatography (SEC) and nuclear magnetic resonance (1H-NMR) spectroscopy, respectively. Then, the complexation with small RNAs was verified, generating polyplexes with sizes ranging from 300 to 600 nm and with encapsulation efficiencies around 80%, depending on the molecular weight of the polymers, their composition, and concentration used. The effect of pH on the morphology of nanoparticles was evaluated by scanning electron microscopy (SEM) being verified that at higher pH values, particles tend to lose their spherical shape. Since this work aims to develop systems for the delivery of non-coding RNAs, studies on RNA protection (contact with RNase, FBS, and Trypsin) and cell viability were also carried out. It was found that they induce some protection against constituents of the cellular environment and have no cellular toxicity. In summary, this research work contributes to the development of pH-sensitive polymers, capable of protecting and encapsulating RNA, in a relatively simple and efficient manner, to further be applied on drug delivery to specific sites where pH may have a critical role, as it can occur in several cancer environments.

Keywords: drug delivery systems, pH-responsive polymers, POEOMA-b-PDPA, small RNAs

Procedia PDF Downloads 238

Authors: Ezzati Givi M., Hoveizi E., Nezhad Marani N.

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Platinum-based anticancer therapeutics are the most widely used drugs in clinical chemotherapy but have major limitations and various side effects in clinical applications. Gonadotoxicity and sterility is one of the most common complications for cancer survivors, which seem to be drug-specific and dose-related. Therefore, many efforts have been dedicated to discovering a new structure of platinum-based anticancer agents with improved therapeutic index, fewer side effects. In this regard, new Pt(II)-phosphane complexes containing heterocyclic thionate ligands (PCTL) have been synthesized, which show more potent antitumor activities in comparison to cisplatin. Cisplatin, the best leading metal-based antitumor drug in the field, induces testicular toxicity on Leydig and Sertoli cells leading to serious side effects such as azoospermia and infertility. Therefore in the present study, we aimed to investigate the cytotoxicity effect of PCTL on mice TM4 Sertoli cells with particular emphasis on the role of autophagy in comparison to cisplatin. In this study, an MTT assay was performed to evaluate the IC50 of PCTL and to analyze the TM3 Leydig cell's viability. Cells morphology was evaluated via invert microscope and Changing in morphology for nuclei swelling or autophagic vacuoles formation were assessed by DAPI and MDC staining. Testosterone production in the culture medium was measured using an ELISA kit. Finally, the expression of Autophagy-related genes, Atg5, Beclin1 and p62, were analyzed by qPCR. Based on the obtained results by MTT, the IC50 value of PCTL was 50 μM in TM3 cells and cytotoxic effects was in a dose- and time-dependent manner. Cells morphological changes investigated by inverted microscopy, DAPI, and MDC staining which showed the cytotoxic concentrations of PCTL was significantly higher than cisplatin in the treated TM3 Leydig cells. The results of PCR showed a lack of expression of the p62, Atg5 and Beclin1 gene in TM3 cells treated with PCTL in comparison to cisplatin and control groups. It should be noted that the effects of 25 μM PCTL concentration on TM3 cells have been associated with increased testosterone production and secretion, which requires further study to explain the possible causes and involved molecular mechanisms. The results of the study showed that the PCTL had less-lethal effects on TM3 cells in comparison to cisplatin and probably did not induce autophagy in TM3 cells.

Keywords: platinum-based anticancer agents, cisplatin, Leydig TM3 cells, autophagy

Procedia PDF Downloads 106

Authors: Milton Ixquiac, Erick Montenegro, Francisco Reynoso, Matthew Schmidt, Thomas Mazur, Tianyu Zhao, Hiram Gay, Geoffrey Hugo, Lauren Henke, Jeff Michael Michalski, Angel Velarde, Vicky de Falla, Franky Reyes, Osmar Hernandez, Edgar Aparicio Ruiz, Baozhou Sun

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Purpose: Radiotherapy departments in low- and middle-income countries (LMICs) like Guatemala have recently introduced intensity-modulated radiotherapy (IMRT). IMRT has become the standard of care in high-income countries (HIC) due to reduced toxicity and improved outcomes in some cancers. The purpose of this work is to show the agreement between the dosimetric results shown in the Dose Volume Histograms (DVH) to the objectives proposed in the adopted protocol. This is the initial experience with an O-ring Linac. Methods and Materials: An O-Linac Linac was installed at our clinic in Guatemala in 2019 and has been used to treat approximately 90 patients daily with IMRT. This Linac is a completely Image Guided Device since to deliver each radiotherapy session must take a Mega Voltage Cone Beam Computerized Tomography (MVCBCT). In each MVCBCT, the Linac deliver 9 UM, and they are taken into account while performing the planning. To start the standardization, the TG263 was employed in the nomenclature and adopted a hypofractionated protocol to treat ChestWall, including supraclavicular nodes achieving 40.05Gy in 15 fractions. The planning was developed using 4 semiarcs from 179-305 degrees. The planner must create optimization volumes for targets and Organs at Risk (OARs); the difficulty for the planner was the dose base due to the MVCBCT. To evaluate the planning modality, we used 30 chestwall cases. Results: The plans created manually achieve the protocol objectives. The protocol objectives are the same as the RTOG1005, and the DHV curves look clinically acceptable. Conclusions: Despite the O-ring Linac doesn´t have the capacity to obtain kv images, the cone beam CT was created using MV energy, the dose delivered by the daily image setup process still without affect the dosimetric quality of the plans, and the dose distribution is acceptable achieving the protocol objectives.

Keywords: hypofrationation, VMAT, chestwall, radiotherapy planning

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Authors: S. Gariani, I. Shyha

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Cutting titanium alloys are usually accompanied with low productivity, poor surface quality, short tool life and high machining costs. This is due to the excessive generation of heat at the cutting zone and difficulties in heat dissipation due to relatively low heat conductivity of this metal. The cooling applications in machining processes are crucial as many operations cannot be performed efficiently without cooling. Improving machinability, increasing productivity, enhancing surface integrity and part accuracy are the main advantages of cutting fluids. Conventional fluids such as mineral oil-based, synthetic and semi-synthetic are the most common cutting fluids in the machining industry. Although, these cutting fluids are beneficial in the industries, they pose a great threat to human health and ecosystem. Vegetable oils (VOs) are being investigated as a potential source of environmentally favourable lubricants, due to a combination of biodegradability, good lubricous properties, low toxicity, high flash points, low volatility, high viscosity indices and thermal stability. Fatty acids of vegetable oils are known to provide thick, strong, and durable lubricant films. These strong lubricating films give the vegetable oil base stock a greater capability to absorb pressure and high load carrying capacity. This paper details preliminary experimental results when turning Ti-6Al-4V. The impact of various VO-based cutting fluids, cutting tool materials, working conditions was investigated. The full factorial experimental design was employed involving 24 tests to evaluate the influence of process variables on average surface roughness (Ra), tool wear and chip formation. In general, Ra varied between 0.5 and 1.56 µm and Vasco1000 cutting fluid presented comparable performance with other fluids in terms of surface roughness while uncoated coarse grain WC carbide tool achieved lower flank wear at all cutting speeds. On the other hand, all tools tips were subjected to uniform flank wear during whole cutting trails. Additionally, formed chip thickness ranged between 0.1 and 0.14 mm with a noticeable decrease in chip size when higher cutting speed was used.

Keywords: cutting fluids, turning, Ti-6Al-4V, vegetable oils, working conditions

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Authors: Bagnoud-Velásquez Mariluz, Damergi Eya, Grandjean Dominique, Frédéric Vogel, Ludwig Christian

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The sustainability of algae to biofuel processes is seriously affected by the energy intensive production of fertilizers. Large amounts of nitrogen and phosphorus are required for a large-scale production resulting in many cases in a negative impact of the limited mineral resources. In order to meet the algal bioenergy opportunity it appears crucial the promotion of processes applying a nutrient recovery and/or making use of renewable sources including waste. Hydrothermal (HT) conversion is a promising and suitable technology for microalgae to generate biofuels. Besides the fact that water is used as a “green” reactant and solvent and that no biomass drying is required, the technology offers a great potential for nutrient recycling. This study evaluated the possibility to treat the water HT effluent by the growth of microalgae while producing renewable algal biomass. As already demonstrated in previous works by the authors, the HT aqueous product besides having N, P and other important nutrients, presents a small fraction of organic compounds rarely studied. Therefore, extracted heteroaromatic compounds in the HT effluent were the target of the present research; they were profiled using GC-MS and LC-MS-MS. The results indicate the presence of cyclic amides, piperazinediones, amines and their derivatives. The most prominent nitrogenous organic compounds (NOC’s) in the extracts were carefully examined by their effect on microalgae, namely 2-pyrrolidinone and β-phenylethylamine (β-PEA). These two substances were prepared at three different concentrations (10, 50 and 150 ppm). This toxicity bioassay used three different microalgae strains: Phaeodactylum tricornutum, Chlorella sorokiniana and Scenedesmus vacuolatus. The confirmed IC50 was for all cases ca. 75ppm. Experimental conditions were set up for the growth of microalgae in the aqueous phase by adjusting the nitrogen concentration (the key nutrient for algae) to fit that one established for a known commercial medium. The values of specific NOC’s were lowered at concentrations of 8.5 mg/L 2-pyrrolidinone; 1mg/L δ-valerolactam and 0.5 mg/L β-PEA. The growth with the diluted HT solution was kept constant with no inhibition evidence. An additional ongoing test is addressing the possibility to apply an integrated water cleanup step making use of the existent hydrothermal catalytic facility.

Keywords: hydrothermal process, microalgae, nitrogenous organic compounds, nutrient recovery, renewable biomass

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Authors: Hernan Arturo Blas López, Gustavo Henndel Lopes, Antonio Carlos Silva Costa Teixeira, Carmen Elena Flores Barreda, Patricia Araujo Pantoja

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Phenols are toxic for life and the environment and may come from many sources. Uncured phenolic monomers present in phenolic resins used as binders in grinding wheels and emery paper can contaminate industrial wastewaters in abrasives manufacture plants. Furthermore, vestiges of resol and novolacs resins generated by wear and tear of abrasives are also possible sources of water contamination by phenolics in these facilities. Fortunately, advanced oxidation by dark Fenton and photo-Fenton techniques are capable of oxidizing phenols and their degradation products up to their mineralization into H₂O and CO₂. The maximal allowable concentrations for phenols in Peruvian waterbodies is very low, such that insufficiently treated effluents from the abrasives industry are a potential environmental noncompliance. The current case study highlights findings obtained during the lab-scale application of Fenton’s and photo-assisted Fenton’s chemistries to real industrial wastewater samples from an abrasives manufacture plant in Peru. The goal was to reduce the phenolic content and sample toxicity. For this purpose, two independent variables-reaction time and effect of ultraviolet radiation–were studied as for their impacts on the concentration of total phenols, total organic carbon (TOC), biological oxygen demand (BOD) and chemical oxygen demand (COD). In this study, diluted samples (1 L) of the industrial effluent were treated with Fenton’s reagent (H₂O₂ and Fe²⁺ from FeSO₄.H₂O) during 10 min in a photochemical batch reactor (Alphatec RFS-500, Brazil) at pH 2.92. In the case of photo-Fenton tests with ultraviolet lamps of 9 W, UV-A, UV-B and UV-C lamps were evaluated. All process conditions achieved 100% of phenols degraded within 5 minutes. TOC, BOD and COD decreased by 49%, 52% and 86% respectively (all processes together). However, Fenton treatment was not capable of reducing BOD, COD and TOC below a certain value even after 10 minutes, contrarily to photo-Fenton. It was also possible to conclude that the processes here studied degrade other compounds in addition to phenols, what is an advantage. In all cases, elevated effluent dilution factors and high amounts of oxidant agent impact negatively the overall economy of the processes here investigated.

Keywords: fenton oxidation, wastewater treatment, phenols, abrasives industry

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Authors: Pirakorn Sukonthaman, Paphitchaya Temphattharachok, Warangkana Thammasanya, Kraichart Tantrakarnarpa, Tanongson Tientavorn

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Agriculture is the main occupation in Thailand. Excessive amount of pesticides are used to increase the products but are toxic to human body. In 2009, Bureau of Epidemiology received 1,691 cases reported with pesticides toxicity (2.66:100,000) which 10.61 % of them is caused by Organophosphate. The purposes are to find factors associated with pesticides used and plasma cholinesterase level and other emerging issues that previous studies did not explain among agricultural workers in Baan Na Yao, Chachoengsao, Thailand. This research was an exploratory mixed method study. Qualitative interviews and quantitative questionnaires were used together in order to gather information from the agricultural workers (mainly cassava and rice farming) directly exposed to pesticides within 2 months simultaneously. Qualitative participants were selected by purposive sampling and a total survey for quantitative ones. The quantitative data was statistically analyzed by using multiple logistic regression model. Qualitative data was transcribed verbatim and thematically analyzed. For qualitative study, 15 participants were interviewed and 300/323 participants (92.88%) were given questionnaires, of which were 175 male and 125 female and 113 among them were spraymen. The prevalence of abnormal plasma cholinesterase level was 92.28% (Safe 7.72% Risky 49.33% and Unsafe 42.95%). Participants with inappropriate behaviors during spraying had a significant association with plasma cholinesterase level (95%CI=1.399-14.858) but other factors such as age, gender, education, attitude and knowledge had no association. They also had encountered various symptoms from pesticides such as fatigue (61%), vertigo (59.67%) and headache (58.86%), etc. Although they had high knowledge and attitude they still had poor behaviors. Moreover, our qualitative component showed that though they had worn the personal protective equipment (PPE) regularly, their PPE was not standard. Not only substandard PPE, but also there were obstacles of wearing such as the hot climate and inconvenience. They misunderstood their symptoms from using pesticides as allergy. Therefore, they did not seek for proper medical check-ups and treatment. This research revealed almost all of the participants have abnormal levels of plasma cholinesterase related especially those with poor behaviors. They also wore PPE but inadequately and misunderstood the symptoms produced by organophosphate use as allergy. Therefore, they did not seek for medical treatment. Occupation health education, modification of PPE and periodic medical checking are ways to make agricultural workers concern and know if there is any progression in a long term.

Keywords: pesticides, plasma cholinesterase level, spraymen, agricultural workers

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Authors: Alexander Heckman, Rohan Goswami, Zachi Attia, Paul Friedman, Peter Noseworthy, Demilade Adedinsewo, Pablo Moreno-Franco, Rickey Carter, Tathagat Narula

Abstract:

Background: Postoperative atrial fibrillation (POAF) is associated with adverse health consequences, higher costs, and longer hospital stays. Utilizing existing predictive models that rely on clinical variables and circulating biomarkers, multiple societies have published recommendations on the treatment and prevention of POAF. Although reasonably practical, there is room for improvement and automation to help individualize treatment strategies and reduce associated complications. Methods and Results: In this retrospective cohort study of solid organ transplant recipients, we evaluated the diagnostic utility of a previously developed AI-based ECG prediction for silent AF on the development of POAF within 30 days of transplant. A total of 2261 non-cardiac transplant patients without a preexisting diagnosis of AF were found to have a 5.8% (133/2261) incidence of POAF. While there were no apparent sex differences in POAF incidence (5.8% males vs. 6.0% females, p=.80), there were differences by race and ethnicity (p<0.001 and 0.035, respectively). The incidence in white transplanted patients was 7.2% (117/1628), whereas the incidence in black patients was 1.4% (6/430). Lung transplant recipients had the highest incidence of postoperative AF (17.4%, 37/213), followed by liver (5.6%, 56/1002) and kidney (3.6%, 32/895) recipients. The AUROC in the sample was 0.62 (95% CI: 0.58-0.67). The relatively low discrimination may result from undiagnosed AF in the sample. In particular, 1,177 patients had at least 1 AI-ECG screen for AF pre-transplant above .10, a value slightly higher than the published threshold of 0.08. The incidence of POAF in the 1104 patients without an elevated prediction pre-transplant was lower (3.7% vs. 8.0%; p<0.001). While this supported the hypothesis that potentially undiagnosed AF may have contributed to the diagnosis of POAF, the utility of the existing AI-ECG screening algorithm remained modest. When the prediction for POAF was made using the first postoperative ECG in the sample without an elevated screen pre-transplant (n=1084 on account of n=20 missing postoperative ECG), the AUROC was 0.66 (95% CI: 0.57-0.75). While this discrimination is relatively low, at a threshold of 0.08, the AI-ECG algorithm had a 98% (95% CI: 97 – 99%) negative predictive value at a sensitivity of 66% (95% CI: 49-80%). Conclusions: This study's principal finding is that the incidence of POAF is rare, and a considerable fraction of the POAF cases may be latent and undiagnosed. The high negative predictive value of AI-ECG screening suggests utility for prioritizing monitoring and evaluation on transplant patients with a positive AI-ECG screening. Further development and refinement of a post-transplant-specific algorithm may be warranted further to enhance the diagnostic yield of the ECG-based screening.

Keywords: artificial intelligence, atrial fibrillation, cardiology, transplant, medicine, ECG, machine learning

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Authors: Vladimir Hovhannisyan, Chen Yuan Dong

Abstract:

Recently nanoparticles (NPs) have been introduced in biomedicine as effective agents for cancer-targeted drug delivery and noninvasive tissue imaging. The most important requirements to these agents are their non-toxicity, biocompatibility and stability. In view of these criteria, the zeolite (ZL) nanoparticles (NPs) may be considered as perfect candidates for biomedical applications. ZLs are crystalline aluminosilicates consisting of oxygen-sharing SiO4 and AlO4 tetrahedral groups united by common vertices in three-dimensional framework and containing pores with diameters from 0.3 to 1.2 nm. Generally, the behavior and physical properties of ZLs are studied by SEM, X-ray spectroscopy, and AFM, whereas optical spectroscopic and microscopic approaches are not effective enough, because of strong scattering in common ZL bulk materials and powders. The light scattering can be reduced by using of ZL NPs. ZL NPs have large external surface area, high dispersibility in both aqueous and organic solutions, high photo- and thermal stability, and exceptional ability to adsorb various molecules and atoms in their nanopores. In this report, using multiphoton microscopy and nonlinear spectroscopy, we investigate nonlinear optical properties of clinoptilolite type of ZL micro- and nanoparticles with average diameters of 2200 nm and 240 nm, correspondingly. Multiphoton imaging is achieved using a laser scanning microscope system (LSM 510 META, Zeiss, Germany) coupled to a femtosecond titanium:sapphire laser (repetition rate- 80 MHz, pulse duration-120 fs, radiation wavelength- 720-820 nm) (Tsunami, Spectra-Physics, CA). Two Zeiss, Plan-Neofluar objectives (air immersion 20×∕NA 0.5 and water immersion 40×∕NA 1.2) are used for imaging. For the detection of the nonlinear response, we use two detection channels with 380-400 nm and 435-700 nm spectral bandwidths. We demonstrate that ZL micro- and nanoparticles can produce nonlinear optical response under the near-infrared femtosecond laser excitation. The interaction of hypericine, chlorin e6 and other dyes with ZL NPs and their photodynamic activity is investigated. Particularly, multiphoton imaging shows that individual ZL NPs particles adsorb Zn-tetraporphyrin molecules, but do not adsorb fluorescein molecules. In addition, nonlinear spectral properties of ZL NPs in native biotissues are studied. Nonlinear microscopy and spectroscopy may open new perspectives in the research and application of ZL NP in biomedicine, and the results may help to introduce novel approaches into the clinical environment.

Keywords: multiphoton microscopy, nanoparticles, nonlinear optics, zeolite

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Authors: Emma Plante, Charles Ekwunwa, Diego Illanes

Abstract:

Introduction: Serum Sickness-Like Reaction (SSLR) is an inflammatory immune response characterized by a rash, polyarthralgias, and fever. SSLR usually occurs in response to a new medication (most commonly antibiotics, anticonvulsants, or antiinflammatory agents) and is believed to involve the formation of drug-specific immune complexes. Here we present a case of a 16-year-old female patient who developed an SSLR in response to the D-mannose-containing over-the-counter supplement, Uqora, used to promote bladder health. Methodology: The methodology for this study included a thorough literature search for other cases of SSLR associated with D-Mannose containing products. Data collection was performed through a review of the patient’s medical record, including history, physical examination, relevant laboratory results, and treatment plan. Findings: A 16-year-old female with a history of overactive bladder and anemia presented with a diffuse urticarial rash, headaches, joint pain, and swelling for three days. Her medications included oral contraceptive pills, iron, mirabegron, UQora, and a probiotic. Physical examination revealed a diffuse urticarial rash, and her musculoskeletal exam revealed swelling and tenderness in her wrists. Her CBC, basic metabolic panel, liver function panel, lyme titers, and urinalysis were all within normal limits. The patient was referred to an allergist, who diagnosed her with SSLR. All medications were discontinued, and she was treated with a 7-day course of prednisone and cetirizine. Her symptoms resolved, and her medications were slowly resumed sequentially over several months. However, UQora triggered a recurrence of her symptoms, and it was identified as the culprit medication. Consequently, UQora was permanently discontinued, and the patient has remained symptom-free. Conclusion: This case report describes the first documented case of SSLR caused by UQora (active ingredient D-mannose). D-Mannose is a monosaccharide found in many plants and fruits, and it is commonly used to prevent urinary tract infections. While the clinical features and timeline, in this case, were typical of SSLR, UQora as the trigger was highly unusual. Clinicians should be aware of the diverse triggers of SSLR and the importance of prompt identification and management to enhance patient safety. It is possible D-mannose was not the trigger, and further research is necessary to better understand the potential therapeutic applications of D-mannose, as well as the potential risks and interactions.

Keywords: serum sickness-like reaction, d-mannose, hypersensitivity reaction, urticaria

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