Search results for: dose gradient

Authors: Maher Z. Mohammed, Barry G. Clarke

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As an alternative to stone column in fine grained soils, it is possible to create stiffened columns of soils using electroosmosis (electroosmotic piles). This program of this research is to establish the effectiveness and efficiency of the process in different soils. The aim of this study is to assess the capability of electroosmosis treatment in a range of composite soils. The combined electroosmotic and preloading equipment developed by Nizar and Clarke (2013) was used with an octagonal array of anodes surrounding a single cathode in a nominal 250mm diameter 300mm deep cylinder of soil and 80mm anode to cathode distance. Copper coiled springs were used as electrodes to allow the soil to consolidate either due to an external vertical applied load or electroosmosis. The equipment was modified to allow the temperature to be monitored during the test. Electroosmotic tests were performed on China Clay Grade E kaolin and calcium bentonite (Bentonex CB) mixed with sand fraction C (BS 1881 part 131) at different ratios by weight; (0, 23, 33, 50 and 67%) subjected to applied voltages (5, 10, 15 and 20). The soil slurry was prepared by mixing the dry soil with water to 1.5 times the liquid limit of the soil mixture. The mineralogical and geotechnical properties of the tested soils were measured before the electroosmosis treatment began. In the electroosmosis cell tests, the settlement, expelled water, variation of electrical current and applied voltage, and the generated heat was monitored during the test time for 24 osmotic tests. Water content was measured at the end of each test. The electroosmotic tests are divided into three phases. In Phase 1, 15 kPa was applied to simulate a working platform and produce a uniform soil which had been deposited as a slurry. 50 kPa was used in Phase 3 to simulate a surcharge load. The electroosmotic treatment was only performed during Phase 2 where a constant voltage was applied through the electrodes in addition to the 15 kPa pressure. This phase was stopped when no further water was expelled from the cell, indicating the electroosmotic process had stopped due to either the degradation of the anode or the flow due to the hydraulic gradient exactly balanced the electroosmotic flow resulting in no flow. Control tests for each soil mixture were carried out to assess the behaviour of the soil samples subjected to only an increase of vertical pressure, which is 15kPa in Phase 1 and 50kPa in Phase 3. Analysis of the experimental results from this study showed a significant dewatering effect on the soil slurries. The water discharged by the electroosmotic treatment process decreased as the sand content increased. Soil temperature increased significantly when electrical power was applied and drops when applied DC power turned off or when the electrode degraded. The highest increase in temperature was found in pure clays at higher applied voltage after about 8 hours of electroosmosis test.

Keywords: electrokinetic treatment, electrical conductivity, electroosmotic consolidation, electroosmosis permeability ratio

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Authors: Paresh Patel, Priya Patel, Vaidehi Sorathiya, Navin Sheth

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The aim of present work was to fabricate Salmeterol Xinafoate (SX) metered dose inhaler (MDI) for asthma and to evaluate the SX loaded solid lipid nanoparticles (SLNs) for pulmonary delivery. Solid lipid nanoparticles can be used to deliver particles to the lungs via MDI. A modified solvent emulsification diffusion technique was used to prepare Salmeterol Xinafoate loaded solid lipid nanoparticles by using compritol 888 ATO as lipid, tween 80 as surfactant, D-mannitol as cryoprotecting agent and L-leucine was used to improve aerosolization behaviour. Box-Behnken design was applied with 17 runs. 3-D surface response plots and contour plots were drawn and optimized formulation was selected based on minimum particle size and maximum % EE. % yield, in vitro diffusion study, scanning electron microscopy, X-ray diffraction, DSC, FTIR also characterized. Particle size, zeta potential analyzed by Zetatrac particle size analyzer and aerodynamic properties was carried out by cascade impactor. Pre convulsion time was examined for control group, treatment group and compare with marketed group. MDI was evaluated for leakage test, flammability test, spray test and content per puff. By experimental design, particle size and % EE found to be in range between 119-337 nm and 62.04-76.77% by solvent emulsification diffusion technique. Morphologically, particles have spherical shape and uniform distribution. DSC & FTIR study showed that no interaction between drug and excipients. Zeta potential shows good stability of SLNs. % respirable fraction found to be 52.78% indicating reach to the deep part of lung such as alveoli. Animal study showed that fabricated MDI protect the lungs against histamine induced bronchospasm in guinea pigs. MDI showed sphericity of particle in spray pattern, 96.34% content per puff and non-flammable. SLNs prepared by Solvent emulsification diffusion technique provide desirable size for deposition into the alveoli. This delivery platform opens up a wide range of treatment application of pulmonary disease like asthma via solid lipid nanoparticles.

Keywords: salmeterol xinafoate, solid lipid nanoparticles, box-behnken design, solvent emulsification diffusion technique, pulmonary delivery

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Authors: Ibrahim M Hassan, Lorna Que, Michael Rutland

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Type I SOD is usually diagnosed by anatomical imaging such as ultrasound, CT and MRCP. However, the types II and III SOD yield negative results despite the presence of significant symptoms. In particular, the type III is difficult to diagnose due to the absence of significant biochemical or anatomical abnormalities. Nuclear Medicine can aid in this diagnostic dilemma by demonstrating functional changes in the bile flow. Low dose Morphine (0.04mg/Kg) stimulates the tone of the sphincter of Oddi (SO) and its usefulness has been shown in diagnosing SOD by causing a delay in bile flow when compared to a non morphine provoked - baseline scan. This work expands on that process by using sublingual GTN at 60 minutes post tracer and morphine injection to relax the SO and induce an improvement in bile outflow, and in some cases show immediate relief of morphine induced abdominal pain. The criteria for positive SOD are as follows: if during the first hour of the morphine provocation showed (1) delayed intrahepatic biliary ducts tracer accumulation; plus (2) delayed appearance but persistent retention of activity in the common bile duct, and (3) delayed bile flow into the duodenum. In addition, patients who required GTN within the first hour to relieve abdominal pain were regarded as highly supportive of the diagnosis. Retrospective analysis of 85 patients (pts) (78F and 6M) referred for suspected SOD (type III) who had been intensively investigated because of recurrent right upper quadrant or abdominal pain post cholecystectomy. 99mTc-HIDA scan with morphine-provocation is performed followed by GTN at 60 minutes post tracer injection and a further thirty minutes of dynamic imaging are acquired. 30 pts were negative. 55 pts were regarded as positive for SOD and 38/55 (60%) of these patients with an abnormal result were further evaluated with a baseline 99mTc-HIDA. As expected, all 38 pts showed better bile flow characteristics than during the morphine provocation. 20/55 (36%) patients were treated by ERCP sphincterotomy and the rest were managed conservatively by medical therapy. In all cases regarded as positive for SOD, the sublingual GTN at 60 minutes showed immediate improvement in bile flow. 11/55(20%) who developed severe post-morphine abdominal pain were relieved by GTN almost instantaneously. We propose that GTN is a useful agent in the diagnosis of SOD when performing 99mTc-HIDA scan and that the satisfactory response to the sublingual GTN could offer additional information in patients who have severe pain at the time the procedure or when presenting to the emergency unit because of biliary pain. And also in determining whether a trial of medical therapy may be used before considering surgery.

Keywords: GTN, HIDA, MORPHINE, SOD

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Authors: Serpil Kilic, Ihsan Burak Cam, Murat Kilic, Timur Tongur

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Interest in the lead (Pb) has considerably increased due to knowledge about the potential toxic effects of this element, recently. Exposure to heavy metals above the acceptable limit affects human health. Indeed, Pb is accumulated through food chains up to toxic concentrations; therefore, it can pose an adverse potential threat to human health. A sensitive and reliable method for determination of Pb element in red pepper were improved in the present study. Samples (33 red pepper products having different brands) were purchased from different markets in Turkey. The selected method validation criteria (linearity, Limit of Detection, Limit of Quantification, recovery, and trueness) demonstrated. Recovery values close to 100% showed adequate precision and accuracy for analysis. According to the results of red pepper analysis, all of the tested lead element in the samples was determined at various concentrations. A Perkin- Elmer ELAN DRC-e model ICP-MS system was used for detection of Pb. Organic red pepper was used to obtain a matrix for all method validation studies. The certified reference material, Fapas chili powder, was digested and analyzed, together with the different sample batches. Three replicates from each sample were digested and analyzed. The results of the exposure levels of the elements were discussed considering the scientific opinions of the European Food Safety Authority (EFSA), which is the European Union’s (EU) risk assessment source associated with food safety. The Target Hazard Quotient (THQ) was described by the United States Environmental Protection Agency (USEPA) for the calculation of potential health risks associated with long-term exposure to chemical pollutants. THQ value contains intake of elements, exposure frequency and duration, body weight and the oral reference dose (RfD). If the THQ value is lower than one, it means that the exposed population is assumed to be safe and 1 < THQ < 5 means that the exposed population is in a level of concern interval. In this study, the THQ of Pb was obtained as < 1. The results of THQ calculations showed that the values were below one for all the tested, meaning the samples did not pose a health risk to the local population. This work was supported by The Scientific Research Projects Coordination Unit of Akdeniz University. Project Number: FBA-2017-2494.

Keywords: lead analyses, red pepper, risk assessment, daily exposure

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Authors: Tais Basaco, Stefanie Pektor, Josue A. Moreno, Matthias Miederer, Andreas Türler

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Radiopharmaceuticals based in monoclonal anti-body (mAb) via chemical linkers have become a potential tool in nuclear medicine because of their specificity and the large variability and availability of therapeutic radiometals. It is important to identify the conjugation sites and number of attached chelator to mAb to obtain radioimmunoconjugates with required immunoreactivity and radiostability. Girentuximab antibody (G250) is a potential candidate for radioimmunotherapy of clear cell carcinomas (RCCs) because it is reactive with CAIX antigen, a transmembrane glycoprotein overexpressed on the cell surface of most ( > 90%) (RCCs). G250 was conjugated with the bifunctional chelating agent DOTA (1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid) via a benzyl-thiocyano group as a linker (p-SCN-Bn-DOTA). DOTA-G250 conjugates were analyzed by size exclusion chromatography (SE-HPLC) and by electrophoresis (SDS-PAGE). The potential site-specific conjugation was identified by liquid chromatography–mass spectrometry (LC/MS-MS) and the number of linkers per molecule of mAb was calculated using the molecular weight (MW) measured by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The average number obtained in the conjugates in non-reduced conditions was between 8-10 molecules of DOTA per molecule of mAb. The average number obtained in the conjugates in reduced conditions was between 1-2 and 3-4 molecules of DOTA per molecule of mAb in the light chain (LC) and heavy chain (HC) respectively. Potential DOTA modification sites of the chelator were identified in lysine residues. The biological activity of the conjugates was evaluated by flow cytometry (FACS) using CAIX negative (SKRC-18) and CAIX positive (SKRC-52). The DOTA-G250 conjugates were labelled with 177Lu with a radiochemical yield > 95% reaching specific activities of 12 MBq/µg. The stability in vitro of different types of radioconstructs was analyzed in human serum albumin (HSA). The radiostability of 177Lu-DOTA-G250 at high specific activity was increased by addition of sodium ascorbate after the labelling. The immunoreactivity was evaluated in vitro and in vivo. Binding to CAIX positive cells (SK-RC-52) at different specific activities was higher for conjugates with less DOTA content. Protein dose was optimized in mice with subcutaneously growing SK-RC-52 tumors using different amounts of 177Lu- DOTA-G250.

Keywords: mass spectrometry, monoclonal antibody, radiopharmaceuticals, radioimmunotheray, renal cancer

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Authors: Martina Šutovská, Marta Jošková, Ivana Kazimierová, Lenka Pappová, Maroš Adamkov, Soňa Fraňová

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Bronchial asthma is characterized by increased bronchoconstrictor responses to provoking agonists, airway inflammation and remodeling. All these processes involve Ca2+ influx through Ca2+-release-activated Ca2+ channels (CRAC) that are widely expressed in immune, respiratory epithelium and airway smooth muscle (ASM) cells. Our previous study pointed on possible therapeutic potency of CRAC blockers using experimental guinea pigs asthma model. Presented work analyzed complex anti-asthmatic effect of long-term administered CRAC blocker, including impact on allergic inflammation, airways hyperreactivity, and remodeling and mucociliary clearance. Ovalbumin-induced allergic inflammation of the airways according to Franova et al. was followed by 14 days lasted administration of CRAC blocker (3-fluoropyridine-4-carboxylic acid, FPCA) in the dose 1.5 mg/kg bw. For comparative purposes salbutamol, budesonide and saline were applied to control groups. The anti-inflammatory effect of FPCA was estimated by serum and bronchoalveolar lavage fluid (BALF) changes in IL-4, IL-5, IL-13 and TNF-α analyzed by Bio-Plex® assay as well as immunohistochemical staining focused on assessment of tryptase and c-Fos positivity in pulmonary samples. The in vivo airway hyperreactivity was evaluated by Pennock et al. and by organ tissue bath methods in vitro. The immunohistochemical changes in ASM actin and collagen III layer as well as mucin secretion evaluated anti-remodeling effect of FPCA. The measurement of ciliary beat frequency (CBF) in vitro using LabVIEW™ Software determined impact on mucociliary clearance. Long-term administration of FPCA to sensitized animals resulted in: i. Significant decrease in cytokine levels, tryptase and c-Fos positivity similar to budesonide effect; ii.Meaningful decrease in basal and bronchoconstrictors-induced in vivo and in vitro airway hyperreactivity comparable to salbutamol; iii. Significant inhibition of airway remodeling parameters; iv. Insignificant changes in CBF. All these findings confirmed complex anti-asthmatic effect of CRAC channels blocker and evidenced these structures as the rational target in the treatment of allergic bronchial asthma.

Keywords: allergic asthma, CRAC channels, cytokines, respiratory epithelium

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Authors: Anik Barua, Rabiul Hossain, Labonno Barua, Rashadul Hossain, Nurul Absar

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Background: Globally, the burden of cancer is increasing consistently. Modern cancer therapies include lots of toxicity in the non-targeted organs reducing the life expectancy of the patients. Hence, scientists are trying to seek noble compounds from natural sources to treat cancer. Objectives: The objectives of the present study are to evaluate the phytochemicals, in vitro antioxidants, and in vivo and in silico anticancer study of various solvent fractions of Tinospora cordifolia (Willd.). Methodology: In this experiment, standard quantitative and qualitative assay methods were used to analyze the phytochemicals. The antioxidant activity was measured using the DPPH and ABTS scavenging methods. The in vivo antitumor activity is evaluated against Ehrlich ascites carcinoma (EAC) cell bearing in Swiss albino mice. In-silico ADME/T and molecular docking study were performed to assess the potential of stated phytochemicals against Transcription Factor STAT3b/DNA Complex of adenocarcinoma. Findings: Phytochemical screening confirmed the presence of flavonoids, alkaloids, glycosides, tannins, and carbohydrates. A significant amount of phenolic (20.19±0.3 mg/g GAE) and flavonoids (9.46±0.18 mg/g GAE) were found in methanolic extract in quantitative screening. Tinospora cordifolia methanolic extract showed promising DPPH and ABTS scavenging activity with the IC50 value of 1222.99 µg/mL and 1534.34 µg/mL, respectively, which was concentration dependent. In vivo anticancer activity in EAC cell-bearing mice showed significant (P < 0.05) percent inhibition of cell growth (60.12±1.22) was found at the highest dose compared with standard drug 5-Fluorouracil (81.18±1.28). Forty-two phytochemicals exhibit notable pharmacokinetics properties and passed drug-likeness screening tests in silico. In molecular docking study, (25S)-3Beta-acetoxy-5-alpha-22-beta-spirost-9(11)-en-12-beta-ol showed docking score (-8.5 kJ/mol) with significant non-bonding interactions with target enzyme. Conclusions: The results were found to be significant and confirmed that the methanolic extract of Tinospora cordifolia has remarkable antitumor activity with antioxidant potential. The Tinospora cordifolia methanolic extract may be considered a potent anticancer agent for advanced research.

Keywords: anticancer, antioxidant, Tinospora cordifolia, EAC cell

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Authors: Saiyed M Ishtiaque, Priyal Dixit

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Objectives: An approach is being suggested to design the filter media to maximize the filtration efficiency with minimum possible pressure drop of composite nonwoven by incorporating the layers of different packing densities induced by fibre of different deniers and punching parameters by using the concept of sequential punching technique in specific order in layered composite nonwoven structure. X-ray computed tomography technique is used to measure the packing density along the thickness of layered nonwoven structure composed by placing the layer of differently oriented fibres influenced by fibres of different deniers and punching parameters in various combinations to minimize the pressure drop at maximum possible filtration efficiency. Methodology Used: This work involves preparation of needle punched layered structure with batts 100g/m2 basis weight having fibre denier, punch density and needle penetration depth as variables to produce 300 g/m2 basis weight nonwoven composite. X-ray computed tomography technique is used to measure the packing density along the thickness of layered nonwoven structure composed by placing the layers of differently oriented fibres influenced by considered variables in various combinations. to minimize the pressure drop at maximum possible filtration efficiencyFor developing layered nonwoven fabrics, batts made of fibre of different deniers having 100g/m2 each basis weight were placed in various combinations. For second set of experiment, the composite nonwoven fabrics were prepared by using 3 denier circular cross section polyester fibre having 64 mm length on needle punched nonwoven machine by using the sequential punching technique to prepare the composite nonwoven fabrics. In this technique, three semi punched fabrics of 100 g/m2 each having either different punch densities or needle penetration depths were prepared for first phase of fabric preparation. These fabrics were later punched altogether to obtain the overall basis weight of 300 g/m2. The total punch density of the composite nonwoven fabric was kept at 200 punches/ cm2 with a needle penetration depth of 10 mm. The layered structures so formed were subcategorised into two groups- homogeneous layered structure in which all the three batts comprising the nonwoven fabric were made from same denier of fibre, punch density and needle penetration depth and were placed in different positions in respective fabric and heterogeneous layered structure in which batts were made from fibres of different deniers, punch densities and needle penetration depths and were placed in different positions. Contributions: The results concluded that reduction in pressure drop is not derived by the overall packing density of the layered nonwoven fabric rather sequencing of layers of specific packing density in layered structure decides the pressure drop. Accordingly, creation of inverse gradient of packing density in layered structure provided maximum filtration efficiency with least pressure drop. This study paves the way for the possibility of customising the composite nonwoven fabrics by the incorporation of differently oriented fibres in constituent layers induced by considered variablres for desired filtration properties.

Keywords: filtration efficiency, layered nonwoven structure, packing density, pressure drop

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Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

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The recent advancements in synthetic chemistry and nanotechnology fostered the development of different nanocarriers for enhanced intracellular delivery of pharmaceutical agents to tumor cells. Polymeric micelles (PMs), characterized by small size, appreciable drug loading capacity (DLC), better accumulation in tumor tissue via enhanced permeability and retention (EPR) effect, and the ability to avoid detection and subsequent clearance by the mononuclear phagocyte (MNP) system, are convenient to improve the poor solubility, slow absorption and non-selective biodistribution of payloads embedded in their hydrophobic cores and hence, enhance the therapeutic efficacy of chemotherapeutic agents. Recently, redox-responsive polymeric micelles have gained significant attention for the delivery and controlled release of anticancer drugs in tumor cells. In this study, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA, and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. The successful synthesis of the copolymers was verified by different spectroscopic techniques. Above the critical micelle concentration, the amphiphilic copolymer, Bi(mPEG-PLGA)-Se₂, self-assembled into stable micelles. The DLS data indicated that the hydrodynamic diameter of the micelles (123.9 ± 0.85 nm) was suitable for extravasation into the tumor cells through the EPR effect. The drug loading content (DLC) and encapsulation efficiency (EE) of DOX-loaded micelles were found to be 6.61 wt% and 54.9%, respectively. The DOX-loaded micelles showed initial burst release accompanied by sustained release trend where 73.94% and 69.54% of encapsulated DOX was released upon treatment with 6mM GSH and 0.1% H₂O₂, respectively. The biocompatible nature of Bi(mPEG-PLGA)-Se₂ copolymer was confirmed by the cell viability study. In addition, the DOX-loaded micelles exhibited significant inhibition against HeLa cells (44.46%), at a maximum dose of 7.5 µg/mL. The fluorescent microscope images of HeLa cells treated with 3 µg/mL (equivalent DOX concentration) revealed efficient internalization and accumulation of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles in the cytosol of cancer cells. In conclusion, the intelligent, biocompatible, and the redox stimuli-responsive behavior of Bi(mPEG-PLGA)-Se₂ copolymer marked the potential applications of diselenide-linked mPEG-PLGA micelles for the delivery and on-demand release of chemotherapeutic agents in cancer cells.

Keywords: anticancer drug delivery, diselenide bond, polymeric micelles, redox-responsive

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Authors: Eunice Christabel Chukwu

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Introduction: Diabetes is a chronic medical condition which is characterized by high levels of glucose in the blood and urine; it is usually diagnosed by means of a glucose tolerance test (GTT). Diabetes can cause a range of health problems if left unmanaged, as it can lead to serious complications. It is essential to manage the condition effectively, particularly in the workplace where the impact on work productivity can be significant. This paper discusses the modelling of optimal control of diabetes in the workplace using a control theory approach. Background: Diabetes mellitus is a condition caused by too much glucose in the blood. Insulin, a hormone produced by the pancreas, controls the blood sugar level by regulating the production and storage of glucose. In diabetes, there may be a decrease in the body’s ability to respond to insulin or a decrease in insulin produced by the pancreas which will lead to abnormalities in the metabolism of carbohydrates, proteins, and fats. In addition to the health implications, the condition can also have a significant impact on work productivity, as employees with uncontrolled diabetes are at risk of absenteeism, reduced performance, and increased healthcare costs. While several interventions are available to manage diabetes, the most effective approach is to control blood glucose levels through a combination of lifestyle modifications and medication. Methodology: The control theory approach involves modelling the dynamics of the system and designing a controller that can regulate the system to achieve optimal performance. In the case of diabetes, the system dynamics can be modelled using a mathematical model that describes the relationship between insulin, glucose, and other variables. The controller can then be designed to regulate the glucose levels to maintain them within a healthy range. Results: The modelling of optimal control of diabetes in the workplace using a control theory approach has shown promising results. The model has been able to predict the optimal dose of insulin required to maintain glucose levels within a healthy range, taking into account the individual’s lifestyle, medication regimen, and other relevant factors. The approach has also been used to design interventions that can improve diabetes management in the workplace, such as regular glucose monitoring and education programs. Conclusion: The modelling of optimal control of diabetes in the workplace using a control theory approach has significant potential to improve diabetes management and work productivity. By using a mathematical model and a controller to regulate glucose levels, the approach can help individuals with diabetes to achieve optimal health outcomes while minimizing the impact of the condition on their work performance. Further research is needed to validate the model and develop interventions that can be implemented in the workplace.

Keywords: mathematical model, blood, insulin, pancreas, model, glucose

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Authors: Chandra Shekhar Majumder, Orin Sultana Jamie

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Background: Dacryocystorhinostomy (DCR) has been a widely accepted surgical intervention for nasolacrimal duct obstructions. Some previous studies demonstrated the potential benefits of the peroperative application of agents like Mitomycin-C (MMC) with DCR to improve surgical outcomes. Relevant studies are rare in Bangladesh, and there are controversies about the dose, duration of MMC, and outcome. Therefore, the present study aimed to investigate the comparative efficacy of DCR with and without MMC in a tertiary hospital in Bangladesh. Objective: The study aims to determine the outcome of a dacryocystorhinostomy with preoperative local use of mitomycin–C. Methods: An analytical study was conducted in the Department of Ophthalmology, Sir Salimullah Medical College & Mitford Hospital, Dhaka, from January 2023 to September 2023. Seventy patients who were admitted for DCR operation were included according to the inclusion and exclusion criteria. Patients were divided into two groups: those who underwent DCR with peroperative administration of 0.2 mg/ml Mitomycin-C for 5 minutes (Group I) and those who underwent DCR alone (Group II). All patients were subjected to detailed history taking, clinical examination, and relevant investigations. All patients underwent DCR according to standard guidelines and ensured the highest peroperative and postoperative care. Then, patients were followed up at 7th POD, 1-month POD, 3 months POD, and 6 months POD to observe the success rate between the two groups by assessing tearing condition, irrigation, height of tear meniscus, and FDDT- test. Data was recorded using a pre-structured questionnaire, and collected data were analyzed using SPSS 23. Results: The mean age of the study patients was 42.17±6.7 (SD) years and 42.29±7.1 (SD) years in Groups I and II, respectively, with no significant difference (p=0.945). At the 6th month’s follow-up, group I patients were observed with 94.3% frequency of symptom-free, 85.6% patency of lacrimal drainage system, 68.6% had tear meniscus <0.1mm and 88.6% had positive Fluorescence Dye Disappearance Test (FDDT test). In group II, 91.4% were symptom-free, 68.6% showed patency, 57.1% had a height of tear meniscus < 0.1 mm, and 85.6% had FDDT test positive. But no statistically significant difference was observed (p<.05). Conclusion: The use of Mitomycin-C preoperatively during DCR offers better postoperative outcomes, particularly in maintaining patency and achieving symptom resolution with more FDDT test positive and improvement of tear meniscus in the MMC group than the control group. However, this study didn’t demonstrate a statistically significant difference between the two groups. Further research with larger sample sizes and longer follow-up periods would be beneficial to corroborate these findings.

Keywords: dacryocystorhinostomy, mitomycin-c, dacryocystitis, nasolacrimal duct obstruction

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Authors: Aminu Mohammed, Shahidul Islam

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Aframomum melegueta K.Schum commonly known as Grains of Paradise has been a popularly used spice in most of the African food preparation. Available data have shown that ethyl acetate fraction from crude ethanolic extract exhibited α-amylase and α-glucosidase inhibitory actions, improved pancreatic β-cell damage and ameliorated insulin resistance in diabetic rats. Additionally, 6-gingerol, 6-shogaol, 6-paradol and oleanolic acid are shown to be the compounds responsible for the antidiabetic action of A. melegueta. However, detail antioxidant potential of this spice in a diabetic animal model has not yet been reported. Thus, the present study investigates the effect of oral consumption of A. melegueta fruit on the in vivo antioxidant status of type 2 diabetes (T2D) model of rats. T2D was induced in rats by feeding a 10% fructose solution ad libitum for two weeks followed by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight (bw)). The animals were orally administered with 150 (DAML) or 300 mg/kg bw (DAMH) of the fraction once daily for four weeks. Data were analyzed by using a statistical software package (SPSS for Windows, version 22, IBM Corporation, NY, USA) using Tukey’s-HSD multiple range post-hoc test. Values were considered significantly different at p < 0.05. According to the data, after four weeks of intervention, diabetic untreated animals showed significantly (p < 0.05) elevation of blood glucose levels. The levels of thiobarbituric acid reactive substances (TBARS) were observed to increase with concomitant reduction of reduced glutathione (GSH) levels in the serum and organs (liver, kidney, heart and pancreas) of diabetic untreated animals. The activities of endogenous antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and reductase) were greatly reduced in the serum and organs of diabetic untreated animals compared to the normal animals. These alterations were reverted to near-normal after the treatment of A. melegueta fruit in the treated groups (DAML & DAMH) within the study period, especially at the dose of 300 mg/kg bw. This potent antioxidant action may partly be attributed to the presence of the 6-Gingerol, 6-shogaol and 6-paradol are known to possess antioxidant action. The results of our study showed that A. melegueta intake improved the antioxidant status of T2D rats and therefore could be used to ameliorate the diabetes-induced oxidative damage.

Keywords: Aframomum melegueta, antioxidant, ethyl acetate extract, type 2 diabetes

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Authors: Rohit Kothari

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Background: Leprosyis a chronic granulomatous diseasecaused by Mycobacterium leprae (M. Lepra). Reactions may interrupt its usual chronic course.Type-1 (T1R)and type-2 lepra reaction(T2R) are acute events and signifytype-IV and type-III hypersensitivity responses, respectively. Various chemokines like CCL3, 5, 11, and CCL24 may be increased during the course of leprosy or during reactions and may serve as markers of early diagnosis, response to therapy, and prognosis. Objective: To find correlation of CCL3, 5, 11, and CCL24 in leprosy patients on multidrug therapy and their family contacts after ruling out active disease during leprosy treatment and during periods of lepra reactions. Methodology: This randomized control trial was conducted in 50 clinico-histopathologically diagnosed cases of leprosy in a tertiary care hospital in Bengaluru, India. 50 of their family contacts were adequately examined and investigated should the need be to rule out active disease. The two study-groups comprised of leprosy cases, and the age, sex, and area of residence matched healthy contactswho were given single-dose rifampicin prophylaxis, respectively. Blood samples were taken at baseline, six months, and after one yearin both the groups (on completion of MDT in leprosy cases)and also during periods of reaction if occurred in leprosy cases. Results: Our study found that at baseline, CCL5, 11, and 24 were higher in leprosy cases as compared to the healthy contacts, and the difference was statistically significant.CCL3 was also found to be higherat baseline in leprosy cases, however, the difference was not statistically significant. At six months and one year, the levels of CCL 5, 11, and 24 reduced, and the difference was statistically significant in leprosy cases, whereas it remained almost static in all the healthy contacts. Twenty patients of leprosy developed lepra reaction during the course of one year, and during reaction, the increase in CCL11 and 24 was statistically significant from baseline, whereas CCL3 and 5 did not rise significantly. One of the healthy contacts developed signs of leprosy in the form of hypopigmented numb patch and was clinico-histopathologically, and CCL11 and 24 were found to be higher with a statistically significant difference from the baseline values. Conclusion: CCL5, 11, and 24 are sensitive markers of diagnosing leprosy, response to MDT, and prognosis and are not increased in healthy contacts. CCL11 and 24 are sensitive markers of lepra reactions and may serve as one of the early diagnostic modalities for identifying lepra reaction and also leprosy in healthy contacts. To the best of our knowledge, this is the first study to evaluate these biomarkers in leprosy cases and their healthy contacts with a follow-up of upto one year with one of them developing the disease, and the same was confirmed based on these biomarkers as well.

Keywords: chemokine profile, healthy contacts, leprosy, lepra reactions

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Authors: Samuele Viaro, Pierre Ricco

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Görtler instabilities generate in boundary layers from an unbalance between pressure and centrifugal forces caused by concave surfaces. Their spatial streamwise evolution influences transition to turbulence. It is therefore important to understand even the early stages where perturbations, still small, grow linearly and could be controlled more easily. This work presents a rigorous theoretical framework for compressible flows using the linearized unsteady boundary region equations, where only the streamwise pressure gradient and streamwise diffusion terms are neglected from the full governing equations of fluid motion. Boundary and initial conditions are imposed through an asymptotic analysis in order to account for the interaction of the boundary layer with free-stream turbulence. The resulting parabolic system is discretize with a second-order finite difference scheme. Realistic flow parameters are chosen from wind tunnel studies performed at supersonic and subsonic conditions. The Mach number ranges from 0.5 to 8, with two different radii of curvature, 5 m and 10 m, frequencies up to 2000 Hz, and vortex spanwise wavelengths from 5 mm to 20 mm. The evolution of the perturbation flow is shown through velocity, temperature, pressure profiles relatively close to the leading edge, where non-linear effects can still be neglected, and growth rate. Results show that a global stabilizing effect exists with the increase of Mach number, frequency, spanwise wavenumber and radius of curvature. In particular, at high Mach numbers curvature effects are less pronounced and thermal streaks become stronger than velocity streaks. This increase of temperature perturbations saturates at approximately Mach 4 flows, and is limited in the early stage of growth, near the leading edge. In general, Görtler vortices evolve closer to the surface with respect to a flat plate scenario but their location shifts toward the edge of the boundary layer as the Mach number increases. In fact, a jet-like behavior appears for steady vortices having small spanwise wavelengths (less than 10 mm) at Mach 8, creating a region of unperturbed flow close to the wall. A similar response is also found at the highest frequency considered for a Mach 3 flow. Larger vortices are found to have a higher growth rate but are less influenced by the Mach number. An eigenvalue approach is also employed to study the amplification of the perturbations sufficiently downstream from the leading edge. These eigenvalue results are compared with the ones obtained through the initial value approach with inhomogeneous free-stream boundary conditions. All of the parameters here studied have a significant influence on the evolution of the instabilities for the Görtler problem which is indeed highly dependent on initial conditions.

Keywords: compressible boundary layers, Görtler instabilities, receptivity, turbulence transition

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Authors: Bollu Mounica

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Background: Nowadays drug related problems were seen very commonly within the health care practice. These could result in the medication errors, adverse events, drug interactions and harm to patients. Pharmacist has an identified role in minimizing and preventing such type of problems. Objectives: To detect the incidence of drug related problems for the hospitalized patient, and to analyze the clinical pharmacist interventions performed during the review of prescription orders of the general medicine, psychiatry, surgery, pediatrics, gynaecology units of a large tertiary care teaching hospital. Methods: It was a retrospective, observational and interventional study. The analysis took place daily with the following parameters: dose, rate of administration, presentation and/or dosage form, presence of inappropriate/unnecessary drugs, necessity of additional medication, more proper alternative therapies, presence of relevant drug interactions, inconsistencies in prescription orders, physical-chemical incompatibilities/solution stability. From this evaluation, the drug therapy problems were classified, as well as the resulting clinical interventions. For a period starting November 2012 until December 2014, the inpatient medication charts and orders were identified and rectified by ward and practicing clinical pharmacists within the inpatient pharmacy services in a tertiary care teaching hospital on routine daily activities. Data was collected and evaluated. The causes of this problem were identified. Results: A total of 360 patients were followed. Male (71.66%) predominance was noted over females (28.33%). Drug related problems were more commonly seen in patients aged in between 31-60. Most of the DRP observed in the study resulted from the dispensing errors (26.11%), improper drug selection (17.22%), followed by untreated indications (14.4%) Majority of the clinical pharmacist recommendations were on need for proper dispensing (26.11%), and drug change (18.05%). Minor significance of DRPs were noted high (41.11 %), whereas (35.27 %) were moderate and (23.61 %) were major. The acceptance rate of intervening clinical pharmacist recommendation and change in drug therapy was found to be high (86.66%). Conclusion: Our study showed that the prescriptions reviewed had some drug therapy problem and the pharmacist interventions have promoted positive changes needed in the prescriptions. In this context, routine participation of clinical pharmacists in clinical medical rounds facilitates the identification of DRPs and may prevent their occurrence.

Keywords: drug related problems, clinical pharmacist, drug prescriptions, drug related problems, intervention

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Authors: Katarzyna Drela, Miroslaw Wielgos, Mikolaj Wrobel, Barbara Lukomska

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Mesenchymal stem cells (MSCs) have a great potential in regenerative medicine. Since the initial number of isolated MSCs is limited, in vitro propagation is often required to reach sufficient numbers of cells for therapeutic applications. During long-term culture MSCs may undergo genetic or epigenetic alterations that subsequently increase the probability of spontaneous malignant transformation. Thus, factors that influence genomic stability of MSCs following long-term expansions need to be clarified before cultured MSCs are employed for clinical application. The aim of our study was to investigate the potential for spontaneous transformation of human neonatal cord blood (HUCB-MSCs) and adult bone marrow (BM-MSCs) derived MSCs. Materials and Methods: HUCB-MSCs and BM-MSCs were isolated by standard Ficoll gradient centrifugations method. Isolated cells were initially plated in high density 106 cells per cm2. After 48 h medium were changed and non-adherent cells were removed. The malignant transformation of MSCs in vitro was evaluated by morphological changes, proliferation rate, ability to enter cell senescence, the telomerase expression and chromosomal abnormality. Proliferation of MSCs was analyzed with WST-1 reduction method and population doubling time (PDT) was calculated at different culture stages. Then the expression pattern of genes characteristic for mesenchymal or epithelial cells, as well as transcriptions factors were examined by RT-PCR. Concomitantly, immunocytochemical analysis of gene-related proteins was employed. Results: Our studies showed that MSCs from all bone marrow isolations ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUCB-MSCs from one of the 15 donors displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. In this sample we observed two different cell phenotypes: one mesenchymal-like exhibited spindle shaped morphology and express specific mesenchymal surface markers (CD73, CD90, CD105, CD166) with low proliferation rate, and the second one with round, densely package epithelial-like cells with significantly increased proliferation rate. The PDT of epithelial-like populations was around 1day and 100% of cells were positive for proliferation marker Ki-67. Moreover, HUCB-MSCs showed a positive expression of human telomerase reverse transcriptase (hTERT), cMYC and exhibit increased number of CFU during the long-term culture in vitro. Furthermore, karyotype analysis revealed chromosomal abnormalities including duplications. Conclusions: Our studies demonstrate that HUCB-MSCs are susceptible to spontaneous malignant transformation during long-term culture. Spontaneous malignant transformation process following in vitro culture has enormous effect on the biosafety issues of future cell-based therapies and regenerative medicine regimens.

Keywords: mesenchymal stem cells, spontaneous, transformation, long-term culture

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Authors: Fatima Zahra Mahjoubi, Abderrahim Khalidi, Mohamed Abdennouri, Omar Cherkaoui, Noureddine Barka

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Industrial effluents are one of the major causes of environmental pollution, especially effluents discharged from various dyestuff manufactures, plastic, and paper making industries. These effluents can give rise to certain hazards and environmental problems for their highly colored suspended organic solid. Dye effluents are not only aesthetic pollutants, but coloration of water by the dyes may affect photochemical activities in aquatic systems by reducing light penetration. It has been also reported that several commonly used dyes are carcinogenic and mutagenic for aquatic organisms. Therefore, removing dyes from effluents is of significant importance. Many adsorbent materials have been prepared in the removal of dyes from wastewater, including anionic clay or layered double hydroxyde. The zinc/aluminium (Zn-AlNO₃), magnesium/aluminium (Mg-AlNO₃) and nickel/aluminium (Ni-AlNO₃) layered double hydroxides (LDHs) were successfully synthesized via coprecipitation method. Samples were characterized by XRD, FTIR, TGA/DTA, TEM and pHPZC analysis. XRD patterns showed a basal spacing increase in the order of Zn-AlNO₃ (8.85Å)> Mg-AlNO₃ (7.95Å)> Ni-AlNO₃ (7.82Å). FTIR spectrum confirmed the presence of nitrate anions in the LDHs interlayer. The TEM images indicated that the Zn-AlNO3 presents circular to shaped particles with an average particle size of approximately 30 to 40 nm. Small plates assigned to sheets with hexagonal form were observed in the case of Mg-AlNO₃. Ni-AlNO₃ display nanostructured sphere in diameter between 5 and 10 nm. The LDHs were used as adsorbents for the removal of methyl orange (MO), as a model dye and for the treatment of an effluent generated by a textile factory. Adsorption experiments for MO were carried out as function of solution pH, contact time and initial dye concentration. Maximum adsorption was occurred at acidic solution pH. Kinetic data were tested using pseudo-first-order and pseudo-second-order kinetic models. The best fit was obtained with the pseudo-second-order kinetic model. Equilibrium data were correlated to Langmuir and Freundlich isotherm models. The best conditions for color and COD removal from textile effluent sample were obtained at lower values of pH. Total color removal was obtained with Mg-AlNO₃ and Ni-AlNO₃ LDHs. Reduction of COD to limits authorized by Moroccan standards was obtained with 0.5g/l LDHs dose.

Keywords: chemical oxygen demand, color removal, layered double hydroxides, textile wastewater treatment

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Authors: Grace C. Kuroki, Yixin Hu, Bailey Surtees, Rebecca Krimins, Nicholas J. Durr, Dara L. Kraitchman

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The purpose of this study was to perform a Phase I veterinary clinical trial with a low-cost, carbon-dioxide-based, passive thaw cryoablation device as proof-of-principle for application in pets and translation to third-world treatment of breast cancer. This study was approved by the institutional animal care and use committee. Client-owned dogs with subcutaneous masses, primarily lipomas or mammary cancers, were recruited for the study. Inclusion was based on clinical history, lesion location, preanesthetic blood work, and fine needle aspirate or biopsy confirmation of mass. Informed consent was obtained from the owners for dogs that met inclusion criteria. Ultrasound assessment of mass extent was performed immediately prior to mass cryoablation. Dogs were placed under general anesthesia and sterilely prepared. A stab incision was created to insert a custom 4.19 OD x 55.9 mm length cryoablation probe (Kubanda Cryotherapy) into the mass. Originally designed for treating breast cancer in low resource settings, this device has demonstrated potential in effectively necrosing subcutaneous masses. A dose escalation study of increasing freeze-thaw cycles (5/4/5, 7/5/7, and 10/7/10 min) was performed to assess the size of the iceball/necrotic extent of cryoablation. Each dog was allowed to recover for ~1-2 weeks before surgical removal of the mass. A single mass was treated in seven dogs (2 mammary masses, a sarcoma, 4 lipomas, and 1 adnexal mass) with most masses exceeding 2 cm in any dimension. Mass involution was most evident in the malignant mammary and adnexal mass. Lipomas showed minimal shrinkage prior to surgical removal, but an area of necrosis was evident along the cryoablation probe path. Gross assessment indicated a clear margin of cryoablation along the cryoprobe independent of tumor type. Detailed histopathology is pending, but complete involution of large lipomas appeared to be unlikely with a 10/7/10 protocol. The low-cost, carbon dioxide-based cryotherapy device permits a minimally invasive technique that may be useful for veterinary applications but is also informative of the unlikely resolution of benign adipose breast masses that may be encountered in third world countries.

Keywords: cryoablation, cryotherapy, interventional oncology, veterinary technology

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Authors: Eyob Seife, Molla Alemayaehu, Tesfalem Teshome, Bereket Seyoum, Behailu Getachew

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Globally, immunization averts between 2 and 3 million deaths yearly, but Vaccine-Preventable Diseases still account for more in Sub-Saharan African countries and takes the majority of under-five deaths yearly, which indicates the need for consistent and on-time information to have evidence-based decision so as to save lives of these vulnerable groups. However, ensuring data of sufficient quality and promoting an information-use culture at the point of collection remains critical and challenging, especially in remote areas where the Ararso district is selected based on a hypothesis of there is a difference in reported and recounted immunization data consistency. Data quality is dependent on different factors where organizational, behavioral, technical and contextual factors are the mentioned ones. A cross-sectional quantitative study was conducted on September 2022 in the Ararso district. The study used the world health organization (WHO) recommended data quality self-assessment (DQS) tools. Immunization tally sheets, registers and reporting documents were reviewed at 4 health facilities (1 health center and 3 health posts) of primary health care units for one fiscal year (12 months) to determine the accuracy ratio, availability and timeliness of reports. The data was collected by trained DQS assessors to explore the quality of monitoring systems at health posts, health centers, and at the district health office. A quality index (QI), availability and timeliness of reports were assessed. Accuracy ratios formulated were: the first and third doses of pentavalent vaccines, fully immunized (FI), TT2+ and the first dose of measles-containing vaccines (MCV). In this study, facility-level results showed poor timeliness at all levels and both over-reporting and under-reporting were observed at all levels when computing the accuracy ratio of registration to health post reports found at health centers for almost all antigens verified. A quality index (QI) of all facilities also showed poor results. Most of the verified immunization data accuracy ratios were found to be relatively better than that of quality index and timeliness of reports. So attention should be given to improving the capacity of staff, timeliness of reports and quality of monitoring system components, namely recording, reporting, archiving, data analysis and using information for decisions at all levels, especially in remote and areas.

Keywords: accuracy ratio, ararso district, quality of monitoring system, regular immunization program, timeliness of reports, Somali region-Ethiopia

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Authors: Anjali Singh, Ashwani Raju, Vandana Devi, Mohmad Mohsin Atique, Satyendra Singh, Munendra Singh

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India is the biggest consumer of mercury and, consequently, a major emitter too. The increasing mercury contamination in India’s water resources has gained widespread attention and, therefore, atmospheric deposition is of critical concern. However, little emphasis was placed on the role of precipitation in the aquatic mercury cycle of the Ganga Alluvial Plain which provides drinking water to nearly 7% of the world’s human population. A majority of the precipitation here occurs primarily in 10% duration of the year in the monsoon season. To evaluate the sources and transportation of mercury, water sample analysis has been conducted from two selected sites near Lucknow, which have a strong hydraulic gradient towards the river. 31 groundwater samples from Jehta village (26°55’15’’N; 80°50’21’’E; 119 m above mean sea level) and 31 river water samples from the Behta Nadi (a tributary of the Gomati River draining into the Ganga River) were collected during the monsoon season on every alternate day between 01 July to 30 August 2019. The total mercury analysis was performed by using Flow Injection Atomic Absorption Spectroscopy (AAS)-Mercury Hybride System, and daily rainfall data was collected from the India Meteorological Department, Amausi, Lucknow. The ambient groundwater and river-water concentrations were both 2-4 ng/L as there is no known geogenic source of mercury found in the area. Before the onset of the monsoon season, the groundwater and the river-water recorded mercury concentrations two orders of magnitude higher than the ambient concentrations, indicating the regional transportation of the mercury from the non-point source into the aquatic environment. Maximum mercury concentrations in groundwater and river-water were three orders of magnitude higher than the ambient concentrations after the onset of the monsoon season characterizing the considerable mobilization and redistribution of mercury by monsoonal precipitation. About 50% of both of the water samples were reported mercury below the detection limit, which can be mostly linked to the low intensity of precipitation in August and also with the dilution factor by precipitation. The highest concentration ( > 1200 ng/L) of mercury in groundwater was reported after 6-days lag from the first precipitation peak. Two high concentration peaks (>1000 ng/L) in river-water were separately correlated with the surface flow and groundwater outflow of mercury. We attribute the elevated mercury concentration in both of the water samples before the precipitation event to mercury originating from the extensive use of agrochemicals in mango farming in the plain. However, the elevated mercury concentration during the onset of monsoon appears to increase in area wetted with atmospherically deposited mercury, which migrated down from surface water to groundwater as downslope migration is a fundamental mechanism seen in rivers of the alluvial plain. The present study underscores the significance of monsoonal precipitation in the transportation of mercury to drinking water resources of the Ganga Alluvial Plain. This study also suggests that future research must be pursued for a better understand of the human health impact of mercury contamination and for quantification of the role of Ganga Alluvial Plain in the Global Mercury Cycle.

Keywords: drinking water resources, Ganga alluvial plain, india, mercury

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Authors: J. O. Ezekwesili-Ofili, L. I. Okorafor, S. C. Nsofor

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Diabetes mellitus is a carbohydrate metabolism disorder due to an absolute or relative deficiency of insulin secretion, action or both. Many known hypoglycaemic drugs are known to produce serious side effects. However, the search for safer and more effective agents has shifted to plant products, including foods and spices. One of such is the rhizome of Curcuma longa or turmeric, which is a spice with high medicinal value. A drawback in the use of C. longa is the poor bioavailability of curcumin, the active ingredient. It has been reported that piperine, an alkaloid present in peppers increases the bioavailability of curcumin. This work therefore investigated the hypoglycaemic and antioxidant effects of ethanolic extract of C. longa rhizomes, alone and with two pepper adjuvants in alloxan-induced diabetic rats. A total of 48 rats were divided into 6 groups of 8 rats each. Groups A–E were induced with diabetes using 150mg/kg body weight of alloxan monohydrate, while group F was normoglycaemic: Group A: Diabetic; fed with 400 mg/g body weight of turmeric extract; group B: Diabetic, fed with 400 mg/kg b. w. and 200mg/kg b. w of ethanolic extract of seeds of Piper guinensee; group C: Diabetic, fed with 400 mg/kg b. w. and 200 mg /kg b. w. of ethanolic extract of seeds of Capsicum annum var cameroun, group D: Diabetic, treated with standard drug, glibenclamide (0.3mg/kg body weight), group E: Diabetic; no treatment i.e. Positive control and group F: non diabetic, no treatment i.e. Negative control. Blood glucose levels were monitored for 14 days using a glucometer. The levels of the antioxidant enzymes; glutathione peroxidase, catalase and superoxide dismutase were also assayed in serum. The ethanolic extracts of C. longa rhizomes at the dose given (400 mg/kg b. w) significantly reduced the blood glucose levels of the diabetic rats (p<0.05) comparable to the standard drug. Co administration of extract of the peppers did not significantly increase the efficiency of the extract, although C. annum var cameroun showed greater effect, though not significantly. The antioxidant effect of the extract was significant in diabetic rats. The use of piperine-containing peppers enhanced the antioxidant effect. Phytochemical analyses of the ethanolic extract of C. longa showed the presence of alkaloids, flavonoids, steroids, saponins, tannins, glycosides, and terpenoids. These results suggest that the ethanolic extract of C. longa had antidiabetic with antioxidant effects and could thus be of benefit in the treatment and management of diabetes as well as ameliorate pro-oxidant effects that may lead to diabetic complications. However, while the addition of piperine did not affect the antidiabetic effect of C. longa, the antioxidant effect was greatly enhanced.

Keywords: antioxidant, Curcuma longa rhizome, hypoglycaemic, pepper adjuvants, piperine

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Authors: Shubham Gogri, Lucia Florescu

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Medical diagnosis and radiotherapy treatment planning using Computed Tomography (CT) rely on the quantitative accuracy and quality of the CT images. At the same time, requirements for CT imaging include reducing the radiation dose exposure to patients and minimizing scanning time. A solution to this is the sparse-view CT technique, based on a reduced number of projection views. This, however, introduces a new problem— the incomplete projection data results in lower quality of the reconstructed images. To tackle this issue, deep learning methods have been applied to enhance the quality of the sparse-view CT images. A first approach involved employing Mir-Net, a dedicated deep neural network designed for image enhancement. This showed promise, utilizing an intricate architecture comprising encoder and decoder networks, along with the incorporation of the Charbonnier Loss. However, this approach was computationally demanding. Subsequently, a specialized Generative Adversarial Network (GAN) architecture, rooted in the Pix2Pix framework, was implemented. This GAN framework involves a U-Net-based Generator and a Discriminator based on Convolutional Neural Networks. To bolster the GAN's performance, both Charbonnier and Wasserstein loss functions were introduced, collectively focusing on capturing minute details while ensuring training stability. The integration of the perceptual loss, calculated based on feature vectors extracted from the VGG16 network pretrained on the ImageNet dataset, further enhanced the network's ability to synthesize relevant images. A series of comprehensive experiments with clinical CT data were conducted, exploring various GAN loss functions, including Wasserstein, Charbonnier, and perceptual loss. The outcomes demonstrated significant image quality improvements, confirmed through pertinent metrics such as Peak Signal-to-Noise Ratio (PSNR) and Structural Similarity Index (SSIM) between the corrected images and the ground truth. Furthermore, learning curves and qualitative comparisons added evidence of the enhanced image quality and the network's increased stability, while preserving pixel value intensity. The experiments underscored the potential of deep learning frameworks in enhancing the visual interpretation of CT scans, achieving outcomes with SSIM values close to one and PSNR values reaching up to 76.

Keywords: generative adversarial networks, sparse view computed tomography, CT image correction, Mir-Net

Procedia PDF Downloads 124

Authors: Ivette Gonzalez-Rivera, Diana B. Paz-Trejo, Oscar Galicia-Castillo, David N. Velazquez-Martinez, Hugo Sanchez-Castillo

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Prolonged exposure to stress can cause disorders related with dysfunction in the prefrontal cortex such as generalized anxiety and depression. These disorders involve alterations in neurotransmitter systems; the serotonergic system—a target of the drugs that are commonly used as a treatment to these disorders—is one of them. Recent studies suggest that 5-HT1A receptors play a pivotal role in the serotonergic system regulation and in stress responses. In the same way, there is increasing evidence that astrocytes are involved in the pathophysiology of stress. The aim of this study was to examine the effects of 8-OH-DPAT, a selective agonist of 5-HT1A receptors, in the behavioral signs of anxiety and anhedonia as well as in the number of astrocytes in the medial prefrontal cortex (mPFC) after exposure to chronic stress. They used 50 male Wistar rats of 250-350 grams housed in standard laboratory conditions and treated in accordance with the ethical standards of use and care of laboratory animals. A protocol of chronic unpredictable stress was used for 10 consecutive days during which the presentation of stressors such as motion restriction, water deprivation, wet bed, among others, were used. 40 rats were subjected to the stress protocol and then were divided into 4 groups of 10 rats each, which were administered 8-OH-DPAT (Tocris, USA) intraperitoneally with saline as vehicle in doses 0.0, 0.3, 1.0 and 2.0 mg/kg respectively. Another 10 rats were not subjected to the stress protocol or the drug. Subsequently, all the rats were measured in an open field test, a forced swimming test, sucrose consume, and a cero maze test. At the end of this procedure, the animals were sacrificed, the brain was removed and the tissue of the mPFC (Bregma: 4.20, 3.70, 2.70, 2.20) was processed in immunofluorescence staining for astrocytes (Anti-GFAP antibody - astrocyte maker, ABCAM). Statistically significant differences were found in the behavioral tests of all groups, showing that the stress group with saline administration had more indicators of anxiety and anhedonia than the control group and the groups with administration of 8-OH-DPAT. Also, a dose dependent effect of 8-OH-DPAT was found on the number of astrocytes in the mPFC. The results show that 8-OH-DPAT can modulate the effect of stress in both behavioral and anatomical level. Also they indicate that 5-HT1A receptors and astrocytes play an important role in the stress response and may modulate the therapeutic effect of serotonergic drugs, so they should be explored as a fundamental part in the treatment of symptoms of stress and in the understanding of the mechanisms of stress responses.

Keywords: anxiety, prefrontal cortex, serotonergic system, stress

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Authors: V. W. Kamgang, A. Van Der Goot, N. C. Bennett, A. Ganswindt

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The roan antelope (Hippotragus equinus) is the second largest antelope species in Africa. These past decades, populations of roan antelope are declining drastically throughout Africa. This situation resulted in the development of intensive breeding programmes for this species in Southern African, where they are popular game ranching herbivores in with increasing numbers in captivity. Nowadays, avoidance of stress is important when managing wildlife to ensure animal welfare. In this regard, a non-invasive approach to monitor the adrenocortical function as a measure of stress would be preferable, since animals are not disturbed during sample collection. However, to date, a non-invasive method has not been established for the roan antelope. In this study, we validated a non-invasive technique to monitor the adrenocortical function in this species. Herein, we performed an adrenocorticotropic hormone (ACTH) stimulation test at Lapalala reserve Wilderness, South Africa, using adult captive roan antelopes to determine the stress-related physiological responses. Two individually housed roan antelope (a male and a female) received an intramuscular injection with Synacthen depot (Norvatis) loaded into a 3ml syringe (Pneu-Dart) at an estimated dose of 1 IU/kg. A total number of 86 faecal samples (male: 46, female: 40) were collected 5 days before and 3 days post-injection. All samples were then lyophilised, pulverized and extracted with 80% ethanol (0,1g/3ml) and the resulting faecal extracts were analysed for immunoreactive faecal glucocorticoid metabolite (fGCM) concentrations using five enzyme immunoassays (EIAs); (i) 11-oxoaetiocholanolone I (detecting 11,17 dioxoandrostanes), (ii) 11-oxoaetiocholanolone II (detecting fGCM with a 5α-pregnane-3α-ol-11one structure), (iii) a 5α-pregnane-3β-11β,21-triol-20-one (measuring 3β,11β-diol CM), (iv) a cortisol and (v) a corticosterone. In both animals, all EIAs detected an increase in fGCM concentration 100% post-ACTH administration. However, the 11-oxoaetiocholanolone I EIA performed best, with a 20-fold increase in the male (baseline: 0.384 µg/g, DW; peak: 8,585 µg/g DW) and a 17-fold in the female (baseline: 0.323 µg/g DW, peak: 7,276 µg/g DW), measured 17 hours and 12 hours post-administration respectively. These results are important as the ability to assess adrenocortical function non-invasively in roan can now be used as an essential prerequisite to evaluate the effects of stressful circumstances; such as variation of environmental conditions or reproduction in other to improve management strategies for the conservation of this iconic antelope species.

Keywords: adrenocorticotropic hormone challenge, adrenocortical function, captive breeding, non-invasive method, roan antelope

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Authors: S. Agarwal, A. Rani

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Catechol is a natural polyphenolic compound that widely exists in higher plants such as teas, vegetables, fruits, tobaccos, and some traditional Chinese medicines. The fly ash-based zeolites are capable of absorbing a wide range of pollutants. But the process of zeolite synthesis is time-consuming and requires technical setups by the industries. The marketed costs of zeolites are quite high restricting its use by small-scale industries for the removal of phenolic compounds. The present research proposes a simple method of alkaline treatment of FA to produce an effective adsorbent for catechol removal from wastewater. The experimental parameter such as pH, temperature, initial concentration and adsorbent dose on the removal of catechol were studied in batch reactor. For this purpose the adsorbent materials were mixed with aqueous solutions containing catechol ranging in 50 – 200 mg/L initial concentrations and then shaken continuously in a thermostatic Orbital Incubator Shaker at 30 ± 0.1 °C for 24 h. The samples were withdrawn from the shaker at predetermined time interval and separated by centrifugation (Centrifuge machine MBL-20) at 2000 rpm for 4 min. to yield a clear supernatant for analysis of the equilibrium concentrations of the solutes. The concentrations were measured with Double Beam UV/Visible spectrophotometer (model Spectrscan UV 2600/02) at the wavelength of 275 nm for catechol. In the present study, the use of low-cost adsorbent (BTFA) derived from coal fly ash (FA), has been investigated as a substitute of expensive methods for the sequestration of catechol. The FA and BTFA adsorbents were well characterized by XRF, FE-SEM with EDX, FTIR, and surface area and porosity measurement which proves the chemical constituents, functional groups and morphology of the adsorbents. The catechol adsorption capacities of synthesized BTFA and native material were determined. The adsorption was slightly increased with an increase in pH value. The monolayer adsorption capacities of FA and BTFA for catechol were 100 mg g⁻¹ and 333.33 mg g⁻¹ respectively, and maximum adsorption occurs within 60 minutes for both adsorbents used in this test. The equilibrium data are fitted by Freundlich isotherm found on the basis of error analysis (RMSE, SSE, and χ²). Adsorption was found to be spontaneous and exothermic on the basis of thermodynamic parameters (ΔG°, ΔS°, and ΔH°). Pseudo-second-order kinetic model better fitted the data for both FA and BTFA. BTFA showed large adsorptive characteristics, high separation selectivity, and excellent recyclability than FA. These findings indicate that BTFA could be employed as an effective and inexpensive adsorbent for the removal of catechol from wastewater.

Keywords: catechol, fly ash, isotherms, kinetics, thermodynamic parameters

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Authors: Preet Shah, Om Shrivastav

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Introduction : In India, Leishmania donovani is the only parasite causing Leishmaniasis. The parasite infects the reticuloendothelial system and is found in the bone marrow, spleen and liver. Treatment of choice is amphotericin-B with sodium stibogluconate being an alternative. Miltefosine is useful in refractory cases. In our case, Leishmaniasis occurred in a person residing in western India (which is quite rare) and it failed to respond to two different drugs (again an uncommon feature) before it finally responded to a third one. Description: A 50 year old lady, a resident of western India, with no history of recent travel, presented with an ulcer on the left side of the nose since 8 months. She was apparently alright 8 months back, when she noticed a small ulcerated lesion on the left ala of the nose which was immediately biopsied. The biopsy revealed amastigotes of Leishmania for which she was administered intra-lesional sodium stibogluconate for 1 month (4 doses every 8 days).Despite this, there was no regression of the ulcer and hence she presented to us for further management. On examination, her vital parameters were normal. Barring an ulcer on the left side of the nose, rest of the examination findings were unremarkable. Complete blood count was normal. Ultrasound abdomen showed hepatomegaly. PET-CT scan showed increased metabolic activity in left ala of nose, hepatosplenomegaly and increased metabolic activity in spleen and bone marrow. Bone marrow biopsy was done which showed hypercellular marrow with erythroid preponderance. Considering a diagnosis of leishmaniasis which had so far been unresponsive to sodium stibogluconate, she was started on liposomal amphotericin-B. At the time of admission, her creatinine level was normal, but it started rising with the administration of liposomal amphotericin-B, hence the dose was reduced. Despite this, creatinine levels did not improve, and she started developing hypokalemia and hypomagnesemia as side effects of the drug, hence further reductions in the dosage were made. Despite a total of 3 weeks of liposomal amphotericin-B, there was no improvement in the ulcer. As had so far failed to respond to sodium stibogluconate and liposomal amphotericin-B, it was decided to start her on miltefosine. She received the miltefosine for a total of 12 weeks. At the end of this duration, there was a marked regression of the cutaneous lesion. Conclusion: Refractoriness to amphotericin-B in leishmaniasis may be seen in up to 5 % cases. Here, an alternative drug such as miltefosine is useful and hence we decided to use it, to which she responded adequately. Furthermore, although leishmaniasis is common in the eastern part of India, it is a relatively unknown entity in the western part of the country with the occurrence being very rare. Because of these 2 reasons, we consider our case to be a unique one.

Keywords: amphotericin-b, leishmaniasis, miltefosine, tropical diseases

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Authors: Kutangila Malundama Succes, Koita Mahamadou

Abstract:

In the context of climate change and demographic pressure, groundwater has emerged as an essential and strategic resource whose sustainability relies on good management. The accuracy and relevance of decisions made in managing these resources depend on the availability and quality of scientific information they must rely on. It is, therefore, more urgent to improve the state of knowledge on groundwater to ensure sustainable management. This study is conducted for the particular case of the aquifers of the transboundary sedimentary basin of Taoudéni in its Burkinabe part. Indeed, Burkina Faso (and the Sahel region in general), marked by low rainfall, has experienced episodes of severe drought, which have justified the use of groundwater as the primary source of water supply. This study aims to improve knowledge of the hydrogeology of this area to achieve sustainable management of transboundary groundwater resources. The methodological approach first described lithological units regarding the extension and succession of different layers. Secondly, the hydrodynamic behavior of these units was studied through the analysis of spatio-temporal variations of piezometric. The data consists of 692 static level measurement points and 8 observation wells located in the usual manner in the area and capturing five of the identified geological formations. Monthly piezometric level chronicles are available for each observation and cover the period from 1989 to 2020. The temporal analysis of piezometric, carried out in comparison with rainfall chronicles, revealed a general upward trend in piezometric levels throughout the basin. The reaction of the groundwater generally occurs with a delay of 1 to 2 months relative to the flow of the rainy season. Indeed, the peaks of the piezometric level generally occur between September and October in reaction to the rainfall peaks between July and August. Low groundwater levels are observed between May and July. This relatively slow reaction of the aquifer is observed in all wells. The influence of the geological nature through the structure and hydrodynamic properties of the layers was deduced. The spatial analysis reveals that piezometric contours vary between 166 and 633 m with a trend indicating flow that generally goes from southwest to northeast, with the feeding areas located towards the southwest and northwest. There is a quasi-concordance between the hydrogeological basins and the overlying hydrological basins, as well as a bimodal flow with a component following the topography and another significant component deeper, controlled by the regional gradient SW-NE. This latter component may present flows directed from the high reliefs towards the sources of Nasso. In the source area (Kou basin), the maximum average stock variation, calculated by the Water Table Fluctuation (WTF) method, varies between 35 and 48.70 mm per year for 2012-2014.

Keywords: hydrodynamic behaviour, taoudeni basin, piezometry, water table fluctuation

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Authors: Sanjay Shukla

Abstract:

Excessive use of antibiotics is a main problem in the treatment of wounds and other chronic infections and antibiotic treatment is frequently non-curative, thus alternative treatment is necessary. Phage therapy is considered one of the most effective approaches to treat multi-drug resistant bacterial pathogens. Infections caused by Staphylococcus aureus are very efficiently controlled with phage cocktails, containing a different individual phages lysate infecting a majority of known pathogenic S. aureus strains. The aim of current study was to investigate the efficiency of a purified phage cocktail for prophylactic as well as therapeutic application in mouse model and in large animals with chronic septic infection of wounds. A total of 150 sewage samples were collected from various livestock farms. These samples were subjected for the isolation of bacteriophage by double agar layer method. A total of 27 sewage samples showed plaque formation by producing lytic activity against S. aureus in double agar overlay method out of 150 sewage samples. In TEM recovered isolates of bacteriophages showed hexagonal structure with tail fiber. In the bacteriophage (ØVS) had an icosahedral symmetry with the head size 52.20 nm in diameter and long tail of 109 nm. Head and tail were held together by connector and can be classified as a member of the Myoviridae family under the order of Caudovirale. Recovered bacteriophage had shown the antibacterial activity against the S. aureus in vitro. Cocktail (ØVS1, ØVS5, ØVS9 and ØVS 27) of phage lysate were tested to know in vivo antibacterial activity as well as the safety profile. Result of mice experiment indicated that the bacteriophage lysate was very safe, did not show any appearance of abscess formation which indicates its safety in living system. The mice were also prophylactically protected against S. aureus when administered with cocktail of bacteriophage lysate just before the administration of S. aureus which indicates that they are good prophylactic agent. The S. aureus inoculated mice were completely recovered by bacteriophage administration with 100% recovery which was very good as compere to conventional therapy. In present study ten chronic cases of wound were treated with phage lysate and follow up of these cases was done regularly up to ten days (at 0, 5 and 10 d). Result indicated that the six cases out of ten showed complete recovery of wounds within 10 d. The efficacy of bacteriophage therapy was found to be 60% which was very good as compared to the conventional antibiotic therapy in chronic septic wounds infections. Thus, the application of lytic phage in single dose proved to be innovative and effective therapy for treatment of septic chronic wounds.

Keywords: phage therapy, phage lysate, antimicrobial resistance, S. aureus

Procedia PDF Downloads 101

Authors: Gurleen Kour, Mowkshi Khullar, B. K. Chandan, Parvinder Pal Singh, Kushalava Reddy Yumpalla, Gurunadham Munagala, Ram A. Vishwakarma, Zabeer Ahmed

Abstract:

New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). Apart from in-vitro potency against the target, physiochemical properties and pharmacokinetic properties play an imperative role in the process of drug discovery. We have identified novel nitroimidazole derivatives with potential activity against mycobacterium tuberculosis. One lead candidates, MCD-017, which showed potent activity against H37Rv strain (MIC=0.5µg/ml) and was further evaluated in the process of drug development. Methods: Basic physicochemical parameters like solubility and lipophilicity (LogP) were evaluated. Thermodynamic solubility was determined in PBS buffer (pH 7.4) using LC/MS-MS. The partition coefficient (Log P) of the compound was determined between octanol and phosphate buffered saline (PBS at pH 7.4) at 25°C by the microscale shake flask method. The compound followed Lipinski’s rule of five, which is predictive of good oral bioavailability and was further evaluated for metabolic stability. In-vitro metabolic stability was determined in rat liver microsomes. The hepatotoxicity of the compound was also determined in HepG2 cell line. In vivo pharmacokinetic profile of the compound after oral dosing was also obtained using balb/c mice. Results: The compound exhibited favorable solubility and lipophilicity. The physical and chemical properties of the compound were made use of as the first determination of drug-like properties. The compound obeyed Lipinski’s rule of five, with molecular weight < 500, number of hydrogen bond donors (HBD) < 5 and number of hydrogen bond acceptors(HBA) not more then 10. The log P of the compound was less than 5 and therefore the compound is predictive of exhibiting good absorption and permeation. Pooled rat liver microsomes were prepared from rat liver homogenate for measuring the metabolic stability. 99% of the compound was not metabolized and remained intact. The compound did not exhibit cytoxicity in hepG2 cells upto 40 µg/ml. The compound revealed good pharmacokinetic profile at a dose of 5mg/kg administered orally with a half life (t1/2) of 1.15 hours, Cmax of 642ng/ml, clearance of 4.84 ml/min/kg and a volume of distribution of 8.05 l/kg. Conclusion : The emergence of multi drug resistance (MDR) and extensively drug resistant (XDR) Tuberculosis emphasize the requirement of novel drugs active against tuberculosis. Thus, the need to evaluate physicochemical and pharmacokinetic properties in the early stages of drug discovery is required to reduce the attrition associated with poor drug exposure. In summary, it can be concluded that MCD-017 may be considered a good candidate for further preclinical and clinical evaluations.

Keywords: mycobacterium tuberculosis, pharmacokinetics, physicochemical properties, hepatotoxicity

Procedia PDF Downloads 437

Authors: Çağrı Bekir Baysal, Göktuğ Burak Çalık

Abstract:

Armored vehicles may have different traction layouts as a result of terrain capabilities and mobility needs. Two main categories of layouts can be separated as wheeled and tracked. Tracked vehicles have superior off-road capabilities but what they gain on terrain performance they lose on mobility front. Wheeled vehicles on the other hand do not have as good terrain capabilities as tracked vehicles but they have superior mobility capabilities such as top speed, range and agility with respect to tracked vehicles. Conventional armored vehicles employ a diesel ICE as main power source. In these vehicles ICE is mechanically connected to the powertrain. This determines the ICE rpm as a result of speed and torque requested by the driver. ICE efficiency changes drastically with torque and speed required and conventional vehicles suffer in terms of fuel consumption because of this. Hybrid electric vehicles employ at least one electric motor in order to improve fuel efficiency. There are different types of hybrid vehicles but main types are Series Hybrid, Parallel Hybrid and Series-Parallel Hybrid. These vehicles introduce an electric motor for traction and also can have a generator electric motor for range extending purposes. Having an electric motor as the traction power source brings the flexibility of either using the ICE as an alternative traction source while it is in efficient range or completely separating the ICE from traction and using it solely considering efficiency. Hybrid configurations have additional advantages for armored vehicles in addition to fuel efficiency. Heat signature, silent operation and prolonged stationary missions can be possible with the help of the high-power battery pack that will be present in the vehicle for hybrid drivetrain. Because of the reasons explained, hybrid armored vehicles are becoming a target area for military and also for vehicle suppliers. In order to have a better idea and starting point when starting a hybrid armored vehicle design, hybrid drivetrain configuration has to be selected after performing a trade-off study. This study has to include vehicle mobility simulations, integration level, vehicle level and performance level criteria. In this study different hybrid traction configurations possible for an 8x8 vehicle is compared using above mentioned criteria set. In order to compare hybrid traction configurations ease of application, cost, weight advantage, reliability, maintainability, redundancy and performance criteria have been used. Performance criteria points have been defined with the help of vehicle simulations and tests. Results of these simulations and tests also help determining required tractive power for an armored vehicle including conditions like trench and obstacle crossing, gradient climb. With the method explained in this study, each configuration is assigned a point for each criterion. This way, correct configuration can be selected objectively for every application. Also, key aspects of armored vehicles, mine protection and ballistic protection will be considered for hybrid configurations. Results are expected to vary for different types of vehicles but it is observed that having longitudinal differential locking capability improves mobility and having high motor count increases complexity in general.

Keywords: armored vehicles, electric drivetrain, electric mobility, hybrid vehicles

Procedia PDF Downloads 66