Search results for: dose gradient
272 Lipid Emulsion versus DigiFab in a Rat Model of Acute Digoxin Toxicity
Authors: Cansu Arslan Turan, Tuba Cimilli Ozturk, Ebru Unal Akoglu, Kemal Aygun, Ecem Deniz Kırkpantur, Ozge Ecmel Onur
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Although the mechanism of action is not well known, Intravenous Lipid Emulsion (ILE) has been shown to be effective in the treatment of lipophilic drug intoxications. It is thought that ILE probably separate the lipophilic drugs from target tissue by creating a lipid-rich compartment in the plasma. The second theory is that ILE provides energy to myocardium with high dose free fatty acids activating the voltage gated calcium channels in the myocytes. In this study, the effects of ILE treatment on digoxin overdose which are frequently observed in emergency departments was searched in an animal model in terms of cardiac side effects and survival. The study was carried out at Yeditepe University, Faculty of Medicine-Experimental Animals Research Center Labs in December 2015. 40 Sprague-Dawley rats weighing 300-400 g were divided into 5 groups randomly. As the pre-treatment, the first group received saline, the second group received lipid, the third group received DigiFab, and the fourth group received DigiFab and lipid. Following that, digoxin was infused to all groups until death except the control group. First arrhythmia and cardiac arrest occurrence times were recorded. As no medication causing arrhythmia was infused, Group 5 was excluded from the statistical analysis performed for the comparisons of first arrhythmia and death time. According to the results although there was no significant difference in the statistical analysis comparing the four groups, as the rats, only exposed to digoxin intoxication were compared with the rats pre-treated with ILE in terms of first arrhythmia time and cardiac arrest occurrence times, significant difference was observed between the groups. According to our results, using DigiFab treatment, intralipid treatment, intralipid and DigiFab treatment for the rats exposed to digoxin intoxication makes no significant difference in terms of the first arrhythmia and death occurrence time. However, it is not possible to say that at the doses we use in the study, ILE treatment might be successful at least as a known antidote. The fact that the statistical significance between the two groups is not observed in the inter-comparisons of all the groups, the study should be repeated in the larger groups.Keywords: arrhytmia, cardiac arrest, DigiFab, digoxin intoxication
Procedia PDF Downloads 229271 Identification and Characterization of in Vivo, in Vitro and Reactive Metabolites of Zorifertinib Using Liquid Chromatography Lon Trap Mass Spectrometry
Authors: Adnan A. Kadi, Nasser S. Al-Shakliah, Haitham Al-Rabiah
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Zorifertinib is a novel, potent, oral, a small molecule used to treat non-small cell lung cancer (NSCLC). zorifertinib is an Epidermal Growth Factor Receptor (EGFR) inhibitor and has good blood–brain barrier permeability for (NSCLC) patients with EGFR mutations. zorifertinibis currently at phase II/III clinical trials. The current research reports the characterization and identification of in vitro, in vivo and reactive intermediates of zorifertinib. Prediction of susceptible sites of metabolism and reactivity pathways (cyanide and GSH) of zorifertinib were performed by the Xenosite web predictor tool. In-vitro metabolites of zorifertinib were performed by incubation with rat liver microsomes (RLMs) and isolated perfused rat liver hepatocytes. Extraction of zorifertinib and it's in vitro metabolites from the incubation mixtures were done by protein precipitation. In vivo metabolism was done by giving a single oral dose of zorifertinib(10 mg/Kg) to Sprague Dawely rats in metabolic cages by using oral gavage. Urine was gathered and filtered at specific time intervals (0, 6, 12, 18, 24, 48, 72,96and 120 hr) from zorifertinib dosing. A similar volume of ACN was added to each collected urine sample. Both layers (organic and aqueous) were injected into liquid chromatography ion trap mass spectrometry(LC-IT-MS) to detect vivozorifertinib metabolites. N-methyl piperizine ring and quinazoline group of zorifertinib undergoe metabolism forming iminium and electro deficient conjugated system respectively, which are very reactive toward nucleophilic macromolecules. Incubation of zorifertinib with RLMs in the presence of 1.0 mM KCN and 1.0 Mm glutathione were made to check reactive metabolites as it is often responsible for toxicities associated with this drug. For in vitro metabolites there were nine in vitro phase I metabolites, four in vitro phase II metabolites, eleven reactive metabolites(three cyano adducts, five GSH conjugates metabolites, and three methoxy metabolites of zorifertinib were detected by LC-IT-MS. For in vivo metabolites, there were eight in vivo phase I, tenin vivo phase II metabolitesofzorifertinib were detected by LC-IT-MS. In vitro and in vivo phase I metabolic pathways wereN- demthylation, O-demethylation, hydroxylation, reduction, defluorination, and dechlorination. In vivo phase II metabolic reaction was direct conjugation of zorifertinib with glucuronic acid and sulphate.Keywords: in vivo metabolites, in vitro metabolites, cyano adducts, GSH conjugate
Procedia PDF Downloads 192270 Retrofitting Insulation to Historic Masonry Buildings: Improving Thermal Performance and Maintaining Moisture Movement to Minimize Condensation Risk
Authors: Moses Jenkins
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Much of the focus when improving energy efficiency in buildings fall on the raising of standards within new build dwellings. However, as a significant proportion of the building stock across Europe is of historic or traditional construction, there is also a pressing need to improve the thermal performance of structures of this sort. On average, around twenty percent of buildings across Europe are built of historic masonry construction. In order to meet carbon reduction targets, these buildings will require to be retrofitted with insulation to improve their thermal performance. At the same time, there is also a need to balance this with maintaining the ability of historic masonry construction to allow moisture movement through building fabric to take place. This moisture transfer, often referred to as 'breathable construction', is critical to the success, or otherwise, of retrofit projects. The significance of this paper is to demonstrate that substantial thermal improvements can be made to historic buildings whilst avoiding damage to building fabric through surface or interstitial condensation. The paper will analyze the results of a wide range of retrofit measures installed to twenty buildings as part of Historic Environment Scotland's technical research program. This program has been active for fourteen years and has seen interventions across a wide range of building types, using over thirty different methods and materials to improve the thermal performance of historic buildings. The first part of the paper will present the range of interventions which have been made. This includes insulating mass masonry walls both internally and externally, warm and cold roof insulation and improvements to floors. The second part of the paper will present the results of monitoring work which has taken place to these buildings after being retrofitted. This will be in terms of both thermal improvement, expressed as a U-value as defined in BS EN ISO 7345:1987, and also, crucially, will present the results of moisture monitoring both on the surface of masonry walls the following retrofit and also within the masonry itself. The aim of this moisture monitoring is to establish if there are any problems with interstitial condensation. This monitoring utilizes Interstitial Hygrothermal Gradient Monitoring (IHGM) and similar methods to establish relative humidity on the surface of and within the masonry. The results of the testing are clear and significant for retrofit projects across Europe. Where a building is of historic construction the use of materials for wall, roof and floor insulation which are permeable to moisture vapor provides both significant thermal improvements (achieving a u-value as low as 0.2 Wm²K) whilst avoiding problems of both surface and intestinal condensation. As the evidence which will be presented in the paper comes from monitoring work in buildings rather than theoretical modeling, there are many important lessons which can be learned and which can inform retrofit projects to historic buildings throughout Europe.Keywords: insulation, condensation, masonry, historic
Procedia PDF Downloads 164269 Pioneering Technology of Night Photo-Stimulation of the Brain Lymphatic System: Therapy of Brain Diseases during Sleep
Authors: Semyachkina-Glushkovskaya Oxana, Fedosov Ivan, Blokhina Inna, Terskov Andrey, Evsukova Arina, Elovenko Daria, Adushkina Viktoria, Dubrovsky Alexander, Jürgen Kurths
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In modern neurobiology, sleep is considered a novel biomarker and a promising therapeutic target for brain diseases. This is due to recent discoveries of the nighttime activation of the brain lymphatic system (BLS), playing an important role in the removal of wastes and toxins from the brain and contributes neuroprotection of the central nervous system (CNS). In our review, we discuss that night stimulation of BLS might be a breakthrough strategy in a new treatment of Alzheimer’s and Parkinson’s disease, stroke, brain trauma, and oncology. Although this research is in its infancy, however, there are pioneering and promising results suggesting that night transcranial photostimulation (tPBM) stimulates more effectively lymphatic removal of amyloid-beta from mouse brain than daily tPBM that is associated with a greater improvement of the neurological status and recognition memory of animals. In our previous study, we discovered that tPBM modulates the tone and permeability of the lymphatic endothelium by stimulating NO formation, promoting lymphatic clearance of wastes and toxins from the brain tissues. We also demonstrate that tPBM can also lead to angio- and lymphangiogenesis, which is another mechanism underlying tPBM-mediated stimulation of BLS. Thus, photo-augmentation of BLS might be a promising therapeutic target for preventing or delaying brain diseases associated with BLS dysfunction. Here we present pioneering technology for simultaneous tPBM in humans and sleep monitoring for stimulation of BLS to remove toxins from CNS and modulation of brain immunity. The wireless-controlled gadget includes a flexible organic light-emitting diode (LED) source that is controlled directly by a sleep-tracking device via a mobile application. The designed autonomous LED source is capable of providing the required therapeutic dose of light radiation at a certain region of the patient’s head without disturbing of sleeping patient. To minimize patients' discomfort, advanced materials like flexible organic LEDs were used. Acknowledgment: This study was supported by RSF project No. 23-75-30001.Keywords: brain diseases, brain lymphatic system, phototherapy, sleep
Procedia PDF Downloads 68268 Drug Therapy Problem and Its Contributing Factors among Pediatric Patients with Infectious Diseases Admitted to Jimma University Medical Center, South West Ethiopia: Prospective Observational Study
Authors: Desalegn Feyissa Desu
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Drug therapy problem is a significant challenge to provide high quality health care service for the patients. It is associated with morbidity, mortality, increased hospital stay, and reduced quality of life. Moreover, pediatric patients are quite susceptible to drug therapy problems. Thus this study aimed to assess drug therapy problem and its contributing factors among pediatric patients diagnosed with infectious disease admitted to pediatric ward of Jimma university medical center, from April 1 to June 30, 2018. Prospective observational study was conducted among pediatric patients with infectious disease admitted from April 01 to June 30, 2018. Drug therapy problems were identified by using Cipolle’s and strand’s drug related problem classification method. Patient’s written informed consent was obtained after explaining the purpose of the study. Patient’s specific data were collected using structured questionnaire. Data were entered into Epi data version 4.0.2 and then exported to statistical software package version 21.0 for analysis. To identify predictors of drug therapy problems occurrence, multiple stepwise backward logistic regression analysis was done. The 95% CI was used to show the accuracy of data analysis and statistical significance was considered at p-value < 0.05. A total of 304 pediatric patients were included in the study. Of these, 226(74.3%) patients had at least one drug therapy problem during their hospital stay. A total of 356 drug therapy problems were identified among two hundred twenty six patients. Non-compliance (28.65%) and dose too low (27.53%) were the most common type of drug related problems while disease comorbidity [AOR=3.39, 95% CI= (1.89-6.08)], Polypharmacy [AOR=3.16, 95% CI= (1.61-6.20)] and more than six days stay in hospital [AOR=3.37, 95% CI= (1.71-6.64) were independent predictors of drug therapy problem occurrence. Drug therapy problems were common in pediatric patients with infectious disease in the study area. Presence of comorbidity, polypharmacy and prolonged hospital stay were the predictors of drug therapy problem in study area. Therefore, to overcome the significant gaps in pediatric pharmaceutical care, clinical pharmacists, Pediatricians, and other health care professionals have to work in collaboration.Keywords: drug therapy problem, pediatric, infectious disease, Ethiopia
Procedia PDF Downloads 149267 Coping with Geological Hazards during Construction of Hydroelectric Projects in Himalaya
Authors: B. D. Patni, Ashwani Jain, Arindom Chakraborty
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The world’s highest mountain range has been forming since the collision of Indian Plate with Asian Plate 40-50 million years ago. The Indian subcontinent has been deeper and deeper in to the rest of Asia resulting upliftment of Himalaya & Tibetan Plateau. The complex domain has become a major challenge for construction of hydro electric projects. The Himalayas are geologically complex & seismically active. Shifting of Indian Plate northwardly and increasing the amount of stresses in the fragile domain which leads to deformation in the form of several fold, faults and upliftment. It is difficult to undergo extensive geological investigation to ascertain the geological problems to be encountered during construction. Inaccessibility of the terrain, high rock cover, unpredictable ground water condition etc. are the main constraints. The hydroelectric projects located in Himalayas have faced many geological and geo-hydrological problems while construction of surface and subsurface works. Based on the experience, efforts have been made to identify the expected geological problems during and after construction of the projects. These have been classified into surface and subsurface problems which include existence of inhomogeneous deep overburden in the river bed or buried valley, abrupt change in bed rock profile, Occurrences of fault zones/shear zones/fractured rock in dam foundation and slope instability in the abutments. The tunneling difficulties are many such as squeezing ground condition, popping, rock bursting, high temperature gradient, heavy ingress of water, existence of shear seams/shear zones and emission of obnoxious gases. However, these problems were mitigated by adopting suitable remedial measures as per site requirement. The support system includes shotcrete, wire mesh, rock bolts, steel ribs, fore-poling, pre-grouting, pipe-roofing, MAI anchors, toe wall, retaining walls, reinforced concrete dowels, drainage drifts, anchorage cum drainage shafts, soil nails, concrete cladding and shear keys. Controlled drilling & blasting, heading & benching, proper drainage network and ventilation system are other remedial measures adopted to overcome such adverse situations. The paper highlights the geological uncertainties and its remedial measures in Himalaya, based on the analysis and evaluation of 20 hydroelectric projects during construction.Keywords: geological problems, shear seams, slope, drilling & blasting, shear zones
Procedia PDF Downloads 398266 The Ameliorative Effects of Nanoencapsulated Triterpenoids from Petri-Dish Cultured Antrodia cinnamomea on Reproductive Function of Diabetic Male Rats
Authors: Sabri Sudirman, Yuan-Hua Hsu, Zwe-Ling Kong
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Male reproductive dysfunction is predominantly due to insulin resistance and hyperglycemia result in inflammation and oxidative stress. Furthermore, nanotechnology provides an alternative approach to improve the bioavailability of natural active food ingredients. Therefore, the aim of this study were to investigate nanoencapsulated triterpenoids from petri-dish cultured Antrodia cinnamomea (PAC) nanoparticles whether it could increase the bioavailability; in addition, the anti-inflammatory and anti-oxidative effects could more effectively ameliorate the reproductive function of diabetic male rats. First, PAC encapsulated in chitosan-silica nanoparticles (Nano-PAC) were prepared by biosilicification method. Scanning electron micrographs confirm the average particle size is about 30 nm, and the encapsulation efficiency is 83.7% by HPLC. Diabetic male Sprague-Dawley rats were induced by high fat diet (40% kcal from fat) and streptozotocin (35 mg/kg). Nano-PAC was administered by oral gavage in three doses (4, 8 and 20 mg/kg) for 6 weeks. Besides, metformin (300 mg/kg) and nanoparticles (Nano) were treated as the positive and negative control respectively. Results indicated that 4 mg/kg Nano-PAC administration for 6 weeks improved hyperglycemia, insulin resistance, and also reduced advanced glycation end products in plasma. In addition, 8 mg/kg Nano-PAC ameliorated morphological of testicular seminiferous tubules, sperm morphology and motility, reactive oxygen species production and mitochondrial membrane potential. Moreover, 20 mg/kg Nano-PAC restored reproductive endocrine system function and increased KiSS-1 level in plasma. In plasma or testis anti-oxidant superoxide dismutase, glutathione peroxidase and catalase were increased whereas malondialdehyde, as well as pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, and interferon-gamma, decreased. Most importantly, 8 mg/kg Nano-PAC down-regulated the oxidative stress induced c-Jun N-terminal kinase (JNK) signaling pathway. Our study successfully nanoencapsulated PAC to form nanoparticles and low-dose Nano-PAC improved diabetes-induced hyperglycemia, inflammation and oxidative stress to ameliorate the reproductive function of diabetic male rats.Keywords: Antrodia cinnamomea, diabetes mellitus, male reproduction, nanoparticles
Procedia PDF Downloads 220265 Design and Synthesis of Copper Doped Zeolite Composite for Antimicrobial Activity and Heavy Metal Removal from Waste Water
Authors: Feleke Terefe Fanta
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The existence of heavy metals and microbial contaminants in aquatic system of Akaki river basin, a sub city of Addis Ababa, has become a public concern as human population increases and land development continues. This is because effluents from chemical and pharmaceutical industries are directly discharged onto surrounding land, irrigation fields and surface water bodies. In the present study, we synthesised zeolites and copper- zeolite composite based adsorbent through cost effective and simple approach to mitigate the problem. The study presents determination of heavy metal content and microbial contamination level of waste water sample collected from Akaki river using zeolites and copper- doped zeolites as adsorbents. The synthesis of copper- zeolite X composite was carried out by ion exchange method of copper ions into zeolites frameworks. The optimum amount of copper ions loaded into the zeolites frameworks were studied using the pore size determination concept via iodine test. The copper- loaded zeolites were characterized by X-ray diffraction (XRD). The XRD analysis showed clear difference in phase purity of zeolite before and after copper ion exchange. The concentration of Cd, Cr, and Pb were determined in waste water sample using atomic absorption spectrophotometry. The mean concentrations of Cd, Cr, and Pb in untreated sample were 0.795, 0.654 and 0.7025 mg/L respectively. The concentration of Cd, Cr, and Pb decreased to 0.005, 0.052 and BDL mg/L for sample treated with bare zeolite X while a further decrease in concentration of Cd, Cr, and Pb (0.005, BDL and BDL) mg/L respectively was observed for the sample treated with copper- zeolite composite. The antimicrobial activity was investigated by exposing the total coliform to the Zeolite X and Copper-modified Zeolite X. Zeolite X and Copper-modified Zeolite X showed complete elimination of microbilas after 90 and 50 minutes contact time respectively. This demonstrates effectiveness of copper- zeolite composite as efficient disinfectant. To understand the mode of heavy metals removal and antimicrobial activity of the copper-loaded zeolites; the adsorbent dose, contact time, temperature was studied. Overall, the results obtained in this study showed high antimicrobial disinfection and heavy metal removal efficiencies of the synthesized adsorbent.Keywords: waste water, copper doped zeolite x, adsorption heavy metal, disinfection
Procedia PDF Downloads 70264 Breast Cancer Cellular Immunotherapies
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 122263 The Effect of Arbutin Powder and Arctostaphylos uvaursi Aqueous Leaf Extract on Synthesis of Melanin by Madurella mycetomatis
Authors: Amina Omer, Ikram Elsiddig
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Arctostaphylos uvaursi is a plant of the family Ericaceae, it’s used in skin care products mostly for its depigmenting action, due to the presence of hydroquinones that are well known inhibitors of tyrosinase, an enzyme involved in melanin biosynthesis in humans. The main hydroquinone found within the A. uvaursi is arbutin, which is found with varying percentage within the plant depending on the season, and area from which the plant is harvested. An in vitro experiment has shown that the arbutin found within the bearberry leaf extract inhibited the biosynthesis of melanin in human melanoma cells and in three-dimensional human skin model. Madurella mycetomatis is filamentous fungus that causes the fungal form of mycetoma known as eumycetoma, with existing anti-fungals and surgery, only 35% of people living eumycetoma are treated, M. mycetomatis has been found to shield itself against the antifungal therapy through the production of melanin decreasing the effectiveness of the therapy, therefore there is a need for a new and more effective therapy. The aim of the study was to investigate and compare the effect of arbutin powder and aqueous extract of A. uvaursi containing arbutin on the biosynthesis of melanin by M. mycetomatis. The experiment was carried out by culturing M. mycetomatis on minimal media composed of 2% agar, 15 mM glucose, 10 mM MgSO4, 29.4 mM KH2PO4, 13 mM glycin and 80mg/l gentamicin, the media was supplied with different concentration of arbutin solution (5, 25 50,and 75mg) and aqueous extract of A. uvaursi to contain arbutin with concentrations (5, 25 50,and 75mg), the plates were incubated for two month and the result was observed by the naked eye. The results revealed that the arbutin powder had an inhibitory effect on melanin synthesis by M. mycetomatis that correlated with its established inhibitory effect on melanin synthesis in humans. The inhibitory effect of arbutin on melanin synthesis by M. mycetomatis was found to be dose dependent. A. uvaursi aqueous leaf extract containing arbutin was also found to decrease melanin production by M. mycetomatis, however plates containing high concentrations of aqueous extract couldn’t be assessed for its melanin inhibitory effect due to the high content of carbohydrates in the extract that promoted the growth of fungi Asperigullus niger rendering the plates unsuitable for visual inspection. In conclusion inhibition of melanin synthesis was observed on the arbutin powder as well as the aqueous extract containing arbutin. A. uvaursi is known to exhibit anti-inflammatory activity, which can aid in wound healing that is beneficial in the chronic inflammation caused by M. mycetomatis.Keywords: arbutin, arctostaphylos, Madurella, melanin
Procedia PDF Downloads 164262 Acute and Subacute Toxicity of the Aqueous Extract of the Bark Stems of Balanites aegyptiaca (L.) Delile in Wistar Rats
Authors: Brahim Sow
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Background: Throughout West Africa, Balanites aegyptiaca (BA), or Zygophyllaceae, is widely used in traditional medicine to treat diabetes, hypertension, inflammation, malaria and liver disorders. In our recent research, we found that BA has nephroprotective potential against diabetes mellitus, hypertension and kidney disorders. However, to our knowledge, no systematic studies have been carried out on its derivative (toxicity) profile. Aim of the study: The study was conducted to assess the potential potency of the hydroalcoholic extract of BA bark in rats by the acute and sub-acute oral route. Materials and methods: Male and female rats in the acute depression study received BA extract orally at single doses of 500 mg/kg, 2000 mg/kg, 3000 mg/kg and 5000 mg/kg (n = 6 per group/sex). To assess acute depression, abnormal behaviour, toxic symptoms, weight and death were observed for 14 consecutive days. For the subacute impairment study, Wistar rats received the extract orally at doses of 125, 250 and 500 mg/kg (n=6 per group/sex) per day for 28 days. Behaviour and body weight were monitored daily. At the end of the treatment period, biochemical, haematological and histopathological examinations were performed, and gross and histopathological examinations of several organs were carried out. To determine the presence or absence of phytochemicals, the BA extract was subjected to gage phage chromatographic examination. Results: The absence of absorption chromatography of BA indicates the absence of cyanide groups. This suggests that the BA extract does not contain toxic substances. No mortality or adverse effects were observed at 5000 mg/kg in the acute depression test. With regard to body weight, general behaviour, relative organ weights, haematological and biochemical parameters, BA extract did not induce any mortality or potentially treatment-related effects in the sub-acute study. The normal architecture of the vital organs was revealed by histopathological examination, indicating the absence of morphological alterations. Conclusion: BA extract administered orally for 28 days at doses up to 500 mg/kg did not cause toxicological damage in rats in the present study. The median lethal dose (LD50) of the extract was estimated to be over 5000 mg/kg in an acute hyperglycaemia study.Keywords: Balanites aegyptiaca L Delile, haematology, biochemistry, rat
Procedia PDF Downloads 71261 Spatial Heterogeneity of Urban Land Use in the Yangtze River Economic Belt Based on DMSP/OLS Data
Authors: Liang Zhou, Qinke Sun
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Taking the Yangtze River Economic Belt as an example, using long-term nighttime lighting data from DMSP/OLS from 1992 to 2012, support vector machine classification (SVM) was used to quantitatively extract urban built-up areas of economic belts, and spatial analysis of expansion intensity index, standard deviation ellipse, etc. was introduced. The model conducts detailed and in-depth discussions on the strength, direction, and type of the expansion of the middle and lower reaches of the economic belt and the key node cities. The results show that: (1) From 1992 to 2012, the built-up areas of the major cities in the Yangtze River Valley showed a rapid expansion trend. The built-up area expanded by 60,392 km², and the average annual expansion rate was 31%, that is, from 9615 km² in 1992 to 70007 km² in 2012. The spatial gradient analysis of the watershed shows that the expansion of urban built-up areas in the middle and lower reaches of the river basin takes Shanghai as the leading force, and the 'bottom-up' model shows an expanding pattern of 'upstream-downstream-middle-range' declines. The average annual rate of expansion is 36% and 35%, respectively. 17% of which the midstream expansion rate is about 50% of the upstream and downstream. (2) The analysis of expansion intensity shows that the urban expansion intensity in the Yangtze River Basin has generally shown an upward trend, the downstream region has continued to rise, and the upper and middle reaches have experienced different amplitude fluctuations. To further analyze the strength of urban expansion at key nodes, Chengdu, Chongqing, and Wuhan in the upper and middle reaches maintain a high degree of consistency with the intensity of regional expansion. Node cities with Shanghai as the core downstream continue to maintain a high level of expansion. (3) The standard deviation ellipse analysis shows that the overall center of gravity of the Yangtze River basin city is located in Anqing City, Anhui Province, and it showed a phenomenon of reciprocating movement from 1992 to 2012. The nighttime standard deviation ellipse distribution range increased from 61.96 km² to 76.52 km². The growth of the major axis of the ellipse was significantly larger than that of the minor axis. It had obvious east-west axiality, in which the nighttime lights in the downstream area occupied in the entire luminosity scale urban system leading position.Keywords: urban space, support vector machine, spatial characteristics, night lights, Yangtze River Economic Belt
Procedia PDF Downloads 110260 The Second Generation of Tyrosine Kinase Inhibitor Afatinib Controls Inflammation by Regulating NLRP3 Inflammasome Activation
Authors: Shujun Xie, Shirong Zhang, Shenglin Ma
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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor
Procedia PDF Downloads 114259 Analyzing Temperature and Pressure Performance of a Natural Air-Circulation System
Authors: Emma S. Bowers
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Perturbations in global environments and temperatures have heightened the urgency of creating cost-efficient, energy-neutral building techniques. Structural responses to this thermal crisis have included designs (including those of the building standard PassivHaus) with airtightness, window placement, insulation, solar orientation, shading, and heat-exchange ventilators as potential solutions or interventions. Limitations in the predictability of the circulation of cooled air through the ambient temperature gradients throughout a structure are one of the major obstacles facing these enhanced building methods. A diverse range of air-cooling devices utilizing varying technologies is implemented around the world. Many of them worsen the problem of climate change by consuming energy. Using natural ventilation principles of air buoyancy and density to circulate fresh air throughout a building with no energy input can combat these obstacles. A unique prototype of an energy-neutral air-circulation system was constructed in order to investigate potential temperature and pressure gradients related to the stack effect (updraft of air through a building due to changes in air pressure). The stack effect principle maintains that since warmer air rises, it will leave an area of low pressure that cooler air will rush in to fill. The result is that warmer air will be expelled from the top of the building as cooler air is directed through the bottom, creating an updraft. Stack effect can be amplified by cooling the air near the bottom of a building and heating the air near the top. Using readily available, mostly recyclable or biodegradable materials, an insulated building module was constructed. A tri-part construction model was utilized: a subterranean earth-tube heat exchanger constructed of PVC pipe and placed in a horizontally oriented trench, an insulated, airtight cube aboveground to represent a building, and a solar chimney (painted black to increase heat in the out-going air). Pressure and temperature sensors were placed at four different heights within the module as well as outside, and data was collected for a period of 21 days. The air pressures and temperatures over the course of the experiment were compared and averaged. The promise of this design is that it represents a novel approach which directly addresses the obstacles of air flow and expense, using the physical principle of stack effect to draw a continuous supply of fresh air through the structure, using low-cost and readily available materials (and zero manufactured energy). This design serves as a model for novel approaches to creating temperature controlled buildings using zero energy and opens the door for future research into the effects of increasing module scale, increasing length and depth of the earth tube, and shading the building. (Model can be provided).Keywords: air circulation, PassivHaus, stack effect, thermal gradient
Procedia PDF Downloads 152258 Algae Biofertilizers Promote Sustainable Food Production and Nutrient Efficiency: An Integrated Empirical-Modeling Study
Authors: Zeenat Rupawalla, Nicole Robinson, Susanne Schmidt, Sijie Li, Selina Carruthers, Elodie Buisset, John Roles, Ben Hankamer, Juliane Wolf
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Agriculture has radically changed the global biogeochemical cycle of nitrogen (N). Fossil fuel-enabled synthetic N-fertiliser is a foundation of modern agriculture but applied to soil crops only use about half of it. To address N-pollution from cropping and the large carbon and energy footprint of N-fertiliser synthesis, new technologies delivering enhanced energy efficiency, decarbonisation, and a circular nutrient economy are needed. We characterised algae fertiliser (AF) as an alternative to synthetic N-fertiliser (SF) using empirical and modelling approaches. We cultivated microalgae in nutrient solution and modelled up-scaled production in nutrient-rich wastewater. Over four weeks, AF released 63.5% of N as ammonium and nitrate, and 25% of phosphorous (P) as phosphate to the growth substrate, while SF released 100% N and 20% P. To maximise crop N-use and minimise N-leaching, we explored AF and SF dose-response-curves with spinach in glasshouse conditions. AF-grown spinach produced 36% less biomass than SF-grown plants due to AF’s slower and linear N-release, while SF resulted in 5-times higher N-leaching loss than AF. Optimised blends of AF and SF boosted crop yield and minimised N-loss due to greater synchrony of N-release and crop uptake. Additional benefits of AF included greener leaves, lower leaf nitrate concentration, and higher microbial diversity and water holding capacity in the growth substrate. Life-cycle-analysis showed that replacing the most effective SF dosage with AF lowered the carbon footprint of fertiliser production from 2.02 g CO₂ (C-producing) to -4.62 g CO₂ (C-sequestering), with a further 12% reduction when AF is produced on wastewater. Embodied energy was lowest for AF-SF blends and could be reduced by 32% when cultivating algae on wastewater. We conclude that (i) microalgae offer a sustainable alternative to synthetic N-fertiliser in spinach production and potentially other crop systems, and (ii) microalgae biofertilisers support the circular nutrient economy and several sustainable development goals.Keywords: bioeconomy, decarbonisation, energy footprint, microalgae
Procedia PDF Downloads 134257 The Efficacy of Albendazole against Soil-Transmitted Helminths and the Impact of Mass Drug Administration of Albendazole and Ivermectin on Health Status
Authors: Mike Yaw Osei-Atweneboana, John Asiedu Larbi, Edward Jenner Tettevi
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Background: The lymphatic filariasis (LF) control programme has been on-going in Ghana since 2000. This community-wide approach involves the use of ivermectin (IVM) and albendazole (ALB). Soil-transmitted helminth (STH) infections control is augmented within this programme; however, in areas where LF is not prevalent, albendazole alone is administered to school children. The purpose of this study was therefore, to determine the efficacy of albendazole against soils transmitted helminths and the impact of mass drug administration of albendazole and ivermectin on the health status of children of school going age and pregnant women. Material/Methods: This was a twelve months longitudinal study. A total of 412 subjects including school children (between the ages of 2-17 years) and pregnant women were randomly selected from four endemic communities in Kpandai district of the Northern region. Coprological assessment for parasites was based on the Kato–Katz technique in both dry and rainy seasons at baseline, 21 days and 3 months post-treatment. Single-dose albendazole treatment was administered to all patients at baseline. Preserved samples are currently under molecular studies to identify possible single nucleotide polymorphism (SNP) within the beta tubulin gene which is associated with benzimidazole resistance. Results: Of all the parasites found (hookworm, Trichuris trichiura, Hymenolepis nana, and Taenia sp.); hookworm was the most prevalent. In the dry season, the overall STHs prevalence at pre-treatment was 29%, while 9% and 13% prevalence was recorded at 21 days, and three months after treatment respectively. However, in the rainy season, the overall STHs prevalence was 8%, while 4% and 12% was recorded at 21 days and three months respectively after ALB treatment. In general, ALB treatment resulted in an overall hookworm egg count reduction rate of 89% in the dry season and 93% in the rainy season, while the T. trichiura egg count reduction rate was 100% in both seasons. Conclusions: STH infections still remains a significant public health burden in Ghana. Hookworm infection seems to respond poorly or sub-optimally to ALB, raising concerns of possible emergence of resistance which may lead to a major setback for the control and elimination of STH infections, especially hookworm infections.Keywords: hookworm, sub-optimal response, albendazole, trichuriasis, soil-transmitted helminths
Procedia PDF Downloads 286256 A Double-Blind, Randomized, Controlled Trial on N-Acetylcysteine for the Prevention of Acute Kidney Injury in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Sara Ataei, Molouk Hadjibabaie, Amirhossein Moslehi, Maryam Taghizadeh-Ghehi, Asieh Ashouri, Elham Amini, Kheirollah Gholami, Alireza Hayatshahi, Mohammad Vaezi, Ardeshir Ghavamzadeh
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Acute kidney injury (AKI) is one of the complications of hematopoietic stem cell transplantation and is associated with increased mortality. N-acetylcysteine (NAC) is a thiol compound with antioxidant and vasodilatory properties that has been investigated for the prevention of AKI in several clinical settings. In the present study, we evaluated the effects of intravenous NAC on the prevention of AKI in allogeneic hematopoietic stem cell transplantation patients. A double-blind randomized placebo-controlled trial was conducted, and 80 patients were recruited to receive 100 mg/kg/day NAC or placebo as intermittent intravenous infusion from day -6 to day +15. AKI was determined on the basis of the Risk-Injury-Failure-Loss-Endstage renal disease and AKI Network criteria as the primary outcome. We assessed urine neutrophil gelatinase-associated lipocalin (uNGAL) on days -6, -3, +3, +9, and +15 as the secondary outcome. Moreover, transplant-related outcomes and NAC adverse reactions were evaluated during the study period. Statistical analysis was performed using appropriate parametric and non-parametric methods including Kaplan–Meier for AKI and generalized estimating equation for uNGAL. At the end of the trial, data from 72 patients were analyzed (NAC: 33 patients and placebo: 39 patients). Participants of each group were not different considering baseline characteristics. AKI was observed in 18% of NAC recipients and 15% of placebo group patients, and the occurrence pattern was not significantly different (p = 0.73). Moreover, no significant difference was observed between groups for uNGAL measures (p = 0.10). Transplant-related outcomes were similar for both groups, and all patients had successful engraftment. Three patients did not tolerate NAC because of abdominal pain, shortness of breath and rash with pruritus and were dropped from the intervention group before transplantation. However, the frequency of adverse reactions was not significantly different between groups. In conclusion, our findings could not show any clinical benefits from high-dose NAC particularly for AKI prevention in allogeneic hematopoietic stem cell transplantation patients.Keywords: acute kidney injury, N-acetylcysteine, hematopoietic stem cell transplantation, urine neutrophil gelatinase-associated lipocalin, randomized controlled trial
Procedia PDF Downloads 429255 Saco Sweet Cherry from Fundão Region, Portugal: Chemical Profile and Health-Promoting Properties
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
Procedia PDF Downloads 311254 Evaluating the Feasibility of Chemical Dermal Exposure Assessment Model
Authors: P. S. Hsi, Y. F. Wang, Y. F. Ho, P. C. Hung
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The aim of the present study was to explore the dermal exposure assessment model of chemicals that have been developed abroad and to evaluate the feasibility of chemical dermal exposure assessment model for manufacturing industry in Taiwan. We conducted and analyzed six semi-quantitative risk management tools, including UK - Control of substances hazardous to health ( COSHH ) Europe – Risk assessment of occupational dermal exposure ( RISKOFDERM ), Netherlands - Dose related effect assessment model ( DREAM ), Netherlands – Stoffenmanager ( STOFFEN ), Nicaragua-Dermal exposure ranking method ( DERM ) and USA / Canada - Public Health Engineering Department ( PHED ). Five types of manufacturing industry were selected to evaluate. The Monte Carlo simulation was used to analyze the sensitivity of each factor, and the correlation between the assessment results of each semi-quantitative model and the exposure factors used in the model was analyzed to understand the important evaluation indicators of the dermal exposure assessment model. To assess the effectiveness of the semi-quantitative assessment models, this study also conduct quantitative dermal exposure results using prediction model and verify the correlation via Pearson's test. Results show that COSHH was unable to determine the strength of its decision factor because the results evaluated at all industries belong to the same risk level. In the DERM model, it can be found that the transmission process, the exposed area, and the clothing protection factor are all positively correlated. In the STOFFEN model, the fugitive, operation, near-field concentrations, the far-field concentration, and the operating time and frequency have a positive correlation. There is a positive correlation between skin exposure, work relative time, and working environment in the DREAM model. In the RISKOFDERM model, the actual exposure situation and exposure time have a positive correlation. We also found high correlation with the DERM and RISKOFDERM models, with coefficient coefficients of 0.92 and 0.93 (p<0.05), respectively. The STOFFEN and DREAM models have poor correlation, the coefficients are 0.24 and 0.29 (p>0.05), respectively. According to the results, both the DERM and RISKOFDERM models are suitable for performance in these selected manufacturing industries. However, considering the small sample size evaluated in this study, more categories of industries should be evaluated to reduce its uncertainty and enhance its applicability in the future.Keywords: dermal exposure, risk management, quantitative estimation, feasibility evaluation
Procedia PDF Downloads 161253 Mating Behaviour and Its Significance in Reproductive Performance of Dysdercus koenigii
Authors: Kamal Kumar Gupta
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The present research work was carried out on Dysdercus koenigii to understand various aspects of reproductive behavior such as mate finding and recognition, mate selection and mating preference, mating receptivity, and prolonged copulation. The studies carried out on mate searching and courtship behaviour of Dysdercus reflected the courtship behaviour in Dysdercus was brief. The opposite sexes are brought together by the pheromone. The males responded to female sex pheromones by showing directional movements toward the sex partners. Change in mating receptivity pattern of female Dysdercus was ascertained using three parameters of mating behaviour i.e. numbers of male’s encounter, the time taken to mate successfully and per cent females responding to mating. It was seen that a receptive female responded positively to the courting males and a high percentage of females mate usually in a very short time span. The females of Dysdercus showed continued mating receptivity throughout their life. The studies pertaining to mate selection by females showed that females generally do not discriminate among males and usually mate with any male they encountered first. The adults of Dysdercus remain in continuous copula up to 72hr. and mate 5-7 time in their life span. Studies pertaining to significance of prolonged mating in the life time reproductive success of the female Dysdercus indicated that fecundity and fertility and oviposition behavior of the female Dysdercus was related to duration of mating. In order to understand sperm precedence, the sterilized males were produced by exposing them to Gamma radiation. Our studies indicated that a dose of 50 Gy of Gamma radiations induced 95% sterility but does not impair the mating behaviour drastically. To understand role of sperms which were transfer during second mating in fertilizing the subsequent egg batches the sperm utilization pattern of doubly mated female was assessed. The females were mated with normal male or sterilized male in a combination. The sperm utilization pattern was determined by P2 value, our studies indicated a very high P2 value of 0.966, and indicated that sperms of last mating were utilized by the female for fertilization. In light of some of the unique reproductive behaviour of Dysdercus koenigii, such as brief courtship behavior, generalized mate selection by the female, continued mating receptivity and a prolonged pre oviposition period, the present studies on sperm precedence provides an explanation to an unusually prolonged copulation in Dysdercus.Keywords: dysdercus koenigii, mating behaviour, reproductive performance, entomology
Procedia PDF Downloads 336252 Influence of Farnesol on Growth and Development of Dysdercus koenigii
Authors: Shailendra Kumar, Kamal Kumar Gupta
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Dysdercus koenigii is an economically important pest of cotton worldwide. The pest damages the crop by sucking sap, staining lint, reducing the oil content of the seeds and deteriorating the quality of cotton. Plant possesses a plethora of secondary metabolites which are used as defense mechanism against herbivores. One of the important categories of such chemicals is insect growth regulators and the intermediates in their biosynthesis. Farnesol belongs to sesquiterpenoid. It is an intermediate in Juvenile hormone biosynthetic pathway in insects has been widely reported in the variety of plants. This chemical can disrupt the normal metabolic function and therefore, affects various life processes of the insects. Present study tested the efficacy of farnesol against Dysdercus koenigii. 2μl of 5% (100µg) and 10% (200µg) of the farnesol was applied topically on the dorsum of thoracic region of the newly emerged fifth instar nymphs of Dysdercus. The treated insects were observed daily for their survival, weight gain, and developmental anomalies for a period of ten days. The results indicated that treatment with 200µg farnesol decreased survival of the insects to 70% after 24h of exposure. At lower doses, no significant decrease in the survival was observed. However, the surviving nymphs showed alteration in growth, development, and metamorphosis. The weight gain in the treated nymphs showed deviation from control. The treated nymphs showed an increase in mortality during subsequent days and increase in the nymphal duration. The number of nymphs undergoing metamorphosis decreased to 46% and 88% in the treatments with the dose of 200µg and 100µg respectively. Severe developmental anomalies were also observed in the treated nymphs. The treated nymphs moulted into supernumerary nymphs, adultoids, adults with exuviae attached and adults with wing deformities. On treatment with 200µg; 26% adultoid, 4% adults with exuviae attached and 12% adults with wing deformed were produced. Treatment with 100µg resulted in production of 34% adultoid, 26% adults with deformed wing and 4% adults with exuviae attached. Many of the treated nymphs did not metamorphose into adults, remained in nymphal stage and died. Our results indicated potential application plant-derived secondary metabolites like farnesol in the management of Dysdercus population.Keywords: development, Dysdercus koenigii, farnesol, survival
Procedia PDF Downloads 350251 Development and Total Error Concept Validation of Common Analytical Method for Quantification of All Residual Solvents Present in Amino Acids by Gas Chromatography-Head Space
Authors: A. Ramachandra Reddy, V. Murugan, Prema Kumari
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Residual solvents in Pharmaceutical samples are monitored using gas chromatography with headspace (GC-HS). Based on current regulatory and compendial requirements, measuring the residual solvents are mandatory for all release testing of active pharmaceutical ingredients (API). Generally, isopropyl alcohol is used as the residual solvent in proline and tryptophan; methanol in cysteine monohydrate hydrochloride, glycine, methionine and serine; ethanol in glycine and lysine monohydrate; acetic acid in methionine. In order to have a single method for determining these residual solvents (isopropyl alcohol, ethanol, methanol and acetic acid) in all these 7 amino acids a sensitive and simple method was developed by using gas chromatography headspace technique with flame ionization detection. During development, no reproducibility, retention time variation and bad peak shape of acetic acid peaks were identified due to the reaction of acetic acid with the stationary phase (cyanopropyl dimethyl polysiloxane phase) of column and dissociation of acetic acid with water (if diluent) while applying temperature gradient. Therefore, dimethyl sulfoxide was used as diluent to avoid these issues. But most the methods published for acetic acid quantification by GC-HS uses derivatisation technique to protect acetic acid. As per compendia, risk-based approach was selected as appropriate to determine the degree and extent of the validation process to assure the fitness of the procedure. Therefore, Total error concept was selected to validate the analytical procedure. An accuracy profile of ±40% was selected for lower level (quantitation limit level) and for other levels ±30% with 95% confidence interval (risk profile 5%). The method was developed using DB-Waxetr column manufactured by Agilent contains 530 µm internal diameter, thickness: 2.0 µm, and length: 30 m. A constant flow of 6.0 mL/min. with constant make up mode of Helium gas was selected as a carrier gas. The present method is simple, rapid, and accurate, which is suitable for rapid analysis of isopropyl alcohol, ethanol, methanol and acetic acid in amino acids. The range of the method for isopropyl alcohol is 50ppm to 200ppm, ethanol is 50ppm to 3000ppm, methanol is 50ppm to 400ppm and acetic acid 100ppm to 400ppm, which covers the specification limits provided in European pharmacopeia. The accuracy profile and risk profile generated as part of validation were found to be satisfactory. Therefore, this method can be used for testing of residual solvents in amino acids drug substances.Keywords: amino acid, head space, gas chromatography, total error
Procedia PDF Downloads 144250 Preparation of Papers - Developing a Leukemia Diagnostic System Based on Hybrid Deep Learning Architectures in Actual Clinical Environments
Authors: Skyler Kim
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An early diagnosis of leukemia has always been a challenge to doctors and hematologists. On a worldwide basis, it was reported that there were approximately 350,000 new cases in 2012, and diagnosing leukemia was time-consuming and inefficient because of an endemic shortage of flow cytometry equipment in current clinical practice. As the number of medical diagnosis tools increased and a large volume of high-quality data was produced, there was an urgent need for more advanced data analysis methods. One of these methods was the AI approach. This approach has become a major trend in recent years, and several research groups have been working on developing these diagnostic models. However, designing and implementing a leukemia diagnostic system in real clinical environments based on a deep learning approach with larger sets remains complex. Leukemia is a major hematological malignancy that results in mortality and morbidity throughout different ages. We decided to select acute lymphocytic leukemia to develop our diagnostic system since acute lymphocytic leukemia is the most common type of leukemia, accounting for 74% of all children diagnosed with leukemia. The results from this development work can be applied to all other types of leukemia. To develop our model, the Kaggle dataset was used, which consists of 15135 total images, 8491 of these are images of abnormal cells, and 5398 images are normal. In this paper, we design and implement a leukemia diagnostic system in a real clinical environment based on deep learning approaches with larger sets. The proposed diagnostic system has the function of detecting and classifying leukemia. Different from other AI approaches, we explore hybrid architectures to improve the current performance. First, we developed two independent convolutional neural network models: VGG19 and ResNet50. Then, using both VGG19 and ResNet50, we developed a hybrid deep learning architecture employing transfer learning techniques to extract features from each input image. In our approach, fusing the features from specific abstraction layers can be deemed as auxiliary features and lead to further improvement of the classification accuracy. In this approach, features extracted from the lower levels are combined into higher dimension feature maps to help improve the discriminative capability of intermediate features and also overcome the problem of network gradient vanishing or exploding. By comparing VGG19 and ResNet50 and the proposed hybrid model, we concluded that the hybrid model had a significant advantage in accuracy. The detailed results of each model’s performance and their pros and cons will be presented in the conference.Keywords: acute lymphoblastic leukemia, hybrid model, leukemia diagnostic system, machine learning
Procedia PDF Downloads 181249 Gold Nanoparticle Conjugated with Andrographolide Ameliorates Viper Venom-Induced Inflammatory Response and Organ Toxicity in Animal Model
Authors: Sourav Ghosh, Antony Gomes
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Since 1894 anti-snake venom serum (ASVS) is the only available treatment against snake envenomation, although there are many side effects and limitations. The need for a supportive treatment was felt for a long time to overcome the side effects and limitations of ASVS. Andrographolide conjugated with gold nanoparticle (A-GNP) has been found to antagonize viper venom-induced local damages. The present study was aimed to study the protective efficacy of A-GNP against Viper venom-induced inflammatory response and organ toxicity in animal model. Ethical clearance was obtained from animal experiments. Physico-chemical characterization of A-GNP was done by DLS (diameter and zeta potential), FE-SEM and XRD. Swiss albino male mice were divided into 4 groups: Gr.1-Sham control, Gr.2- Russell’s Viper venom (RVV) control, Gr.3- andrographolide treated and Gr.4- A-GNP treated. The 1/5th minimum lethal dose of RVV (500µg/kg, s.c.) was induced in animals of group 2, 3 & 4 animals, followed by treatment with andrographolide (100mg/kg, i.p.) and A-GNP (100mg/kg, i.v.) in group 3 & 4 animals, respectively. Blood was collected after 18 h, serum was prepared, and inflammatory markers (IL 1β, 6, 17a, 10, TNF α) and biochemical markers (AST, ACP, LDH, urea, creatinine) were assessed. Values were expressed as mean±SEM (n=4), one way ANOVA was done, P<0.05 was considered as statistically significant. DLS size showed the hydrodynamic diameter of A-GNP to be 230-260nm with polydispersity index of 0.103 and zeta potential was -18.32mV. XRD data confirmed the presence of crystalline gold in A-GNP, and FESEM indicated the presence of nearly spherical particle with size18-24nm.Treatment with A-GNP significantly decreased viper venom-induced proinflammatory markers (IL 1β, 6, 17, TNF α) increased anti-inflammatory markers (IL 10) and decreased organ toxicity markers (AST, ACP, LDH, urea, creatinine) in animal model. Venom neutralization efficacy of A-GNP was > andrographolide, which confirmed the increased efficacy of andrographolide after gold nanoparticle conjugation. Venom neutralization by A-GNP was due to anti-oxidant/anti-inflammatory activity of andrographolide, which showed increased efficacy after gold nanoparticle tagging. Thus, A-GNP may serve as a supportive therapy in snake-bite (against inflammatory response and organ toxicity) subject to further detail studies.Keywords: andrographolide, gold nanoparticle, inflammatory response, organ toxicity, snake venom, snake venom neutralization, viper venom
Procedia PDF Downloads 368248 Soybean Seed Composition Prediction From Standing Crops Using Planet Scope Satellite Imagery and Machine Learning
Authors: Supria Sarkar, Vasit Sagan, Sourav Bhadra, Meghnath Pokharel, Felix B.Fritschi
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Soybean and their derivatives are very important agricultural commodities around the world because of their wide applicability in human food, animal feed, biofuel, and industries. However, the significance of soybean production depends on the quality of the soybean seeds rather than the yield alone. Seed composition is widely dependent on plant physiological properties, aerobic and anaerobic environmental conditions, nutrient content, and plant phenological characteristics, which can be captured by high temporal resolution remote sensing datasets. Planet scope (PS) satellite images have high potential in sequential information of crop growth due to their frequent revisit throughout the world. In this study, we estimate soybean seed composition while the plants are in the field by utilizing PlanetScope (PS) satellite images and different machine learning algorithms. Several experimental fields were established with varying genotypes and different seed compositions were measured from the samples as ground truth data. The PS images were processed to extract 462 hand-crafted vegetative and textural features. Four machine learning algorithms, i.e., partial least squares (PLSR), random forest (RFR), gradient boosting machine (GBM), support vector machine (SVM), and two recurrent neural network architectures, i.e., long short-term memory (LSTM) and gated recurrent unit (GRU) were used in this study to predict oil, protein, sucrose, ash, starch, and fiber of soybean seed samples. The GRU and LSTM architectures had two separate branches, one for vegetative features and the other for textures features, which were later concatenated together to predict seed composition. The results show that sucrose, ash, protein, and oil yielded comparable prediction results. Machine learning algorithms that best predicted the six seed composition traits differed. GRU worked well for oil (R-Squared: of 0.53) and protein (R-Squared: 0.36), whereas SVR and PLSR showed the best result for sucrose (R-Squared: 0.74) and ash (R-Squared: 0.60), respectively. Although, the RFR and GBM provided comparable performance, the models tended to extremely overfit. Among the features, vegetative features were found as the most important variables compared to texture features. It is suggested to utilize many vegetation indices for machine learning training and select the best ones by using feature selection methods. Overall, the study reveals the feasibility and efficiency of PS images and machine learning for plot-level seed composition estimation. However, special care should be given while designing the plot size in the experiments to avoid mixed pixel issues.Keywords: agriculture, computer vision, data science, geospatial technology
Procedia PDF Downloads 128247 Experiences of Community Midwives Receiving Helping Baby Breathe Training Through the Low Dose High-frequency Approach in Gujrat, Pakistan
Authors: Anila Naz, Arusa Lakhani, Kiran Mubeen, Yasmeen Amarsi
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Pakistan's neonatal mortality rate has the highest proportion in the South Asian region and it is higher in the rural areas as compared to the urban areas. Poor resuscitation techniques and lack of basic newborn resuscitation skills in birth attendants, are contributing factors towards neonatal deaths. Based on the significant outcomes of the Helping Baby Breath (HBB) training, a similar training was implemented for Community Midwives (CMWs) in a low resource setting in Gujrat, Pakistan, to improve their knowledge and skills. The training evaluation was conducted and participant feedback was obtained through both qualitative and quantitative methods. The findings of the quantitative assessment of the training evaluation will be published elsewhere. This paper presents the qualitative evaluation of the training. Objective: The objective of the study was to determine the perceptions of HBB trained CMWs about the effectiveness of the HBB training, and the challenges faced in the implementation of HBB skills for newborn resuscitation, at their work settings. The qualitative descriptive design was used in this study. The purposive sampling technique was chosen to recruit midwives and key informants as participants of the training. Interviews were conducted by using a semi-structured interview guide. The study included a total of five interviews: two focus group interviews for CMWs (10 in each group), and three individual interviews of key informants. The content analysis of the qualitative data yielded three themes: the effectiveness of training, challenges, and suggestions. The findings revealed that the HBB training was effective for the CMWs in terms of its usability, regarding improvement in newborn resuscitation knowledge and skills. Moreover, it enhanced confidence and satisfaction in CMWs. However, less volume of patients was a challenge for a few CMWs with regards to practicing their skills. Due to the inadequate number of patients and less opportunities of practice for several CMWs, they required such trainings frequently, in order to maintain their competency. The CMWs also recommended that HBB training should be part of the Midwifery program curriculum. Moreover, similar trainings were also recommended for other healthcare providers working in low resource settings, including doctors and nurses.Keywords: neonatal resuscitation technique, helping baby breathe, community midwives, training evaluation
Procedia PDF Downloads 92246 Recycling Waste Product for Metal Removal from Water
Authors: Saidur R. Chowdhury, Mamme K. Addai, Ernest K. Yanful
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The research was performed to assess the potential of nickel smelter slag, an industrial waste, as an adsorbent in the removal of metals from aqueous solution. An investigation was carried out for Arsenic (As), Copper (Cu), lead (Pb) and Cadmium (Cd) adsorption from aqueous solution. Smelter slag was obtain from Ni ore at the Vale Inco Ni smelter in Sudbury, Ontario, Canada. The batch experimental studies were conducted to evaluate the removal efficiencies of smelter slag. The slag was characterized by surface analytical techniques. The slag contained different iron oxides and iron silicate bearing compounds. In this study, the effect of pH, contact time, particle size, competition by other ions, slag dose and distribution coefficient were evaluated to measure the optimum adsorption conditions of the slag as an adsorbent for As, Cu, Pb and Cd. The results showed 95-99% removal of As, Cu, Pb, and almost 50-60% removal of Cd, while batch experimental studies were conducted at 5-10 mg/L of initial concentration of metals, 10 g/L of slag doses, 10 hours of contact time and 170 rpm of shaking speed and 25oC condition. The maximum removal of Arsenic (As), Copper (Cu), lead (Pb) was achieved at pH 5 while the maximum removal of Cd was found after pH 7. The column experiment was also conducted to evaluate adsorption depth and service time for metal removal. This study also determined adsorption capacity, adsorption rate and mass transfer rate. The maximum adsorption capacity was found to be 3.84 mg/g for As, 4 mg/g for Pb, and 3.86 mg/g for Cu. The adsorption capacity of nickel slag for the four test metals were in decreasing order of Pb > Cu > As > Cd. Modelling of experimental data with Visual MINTEQ revealed that saturation indices of < 0 were recorded in all cases suggesting that the metals at this pH were under- saturated and thus in their aqueous forms. This confirms the absence of precipitation in the removal of these metals at the pHs. The experimental results also showed that Fe and Ni leaching from the slag during the adsorption process was found to be very minimal, ranging from 0.01 to 0.022 mg/L indicating the potential adsorbent in the treatment industry. The study also revealed that waste product (Ni smelter slag) can be used about five times more before disposal in a landfill or as a stabilization material. It also highlighted the recycled slags as a potential reactive adsorbent in the field of remediation engineering. It also explored the benefits of using renewable waste products for the water treatment industry.Keywords: adsorption, industrial waste, recycling, slag, treatment
Procedia PDF Downloads 140245 Beneficial Effects of Whey Protein Concentrate in Venous Thrombosis
Authors: Anna Tokajuk, Agnieszka Zakrzeska, Ewa Chabielska, Halina Car
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Whey is a by-product generated mainly in the production of cheese and casein. Powder forms of whey are used widely in the food industry as well as a high-protein food for infants, for convalescents, by athletes and especially by bodybuilders to increase muscle mass during exercise. Whey protein concentrate-80 (WPC-80) is a source of bioactive peptides with beneficial effects on the cardiovascular system. It is known that whey proteins health beneficial properties include antidiabetic, blood pressure lowering, improving cardiovascular system function, antibacterial, antiviral and other effects. To study its influence on the development of thrombosis, venous thrombosis model was performed according to the protocol featured by Reyers with modification by Chabielska and Gromotowicz. Male Wistar-Crl: WI (Han) rats from researched groups were supplemented with two doses of WPC-80 (0.3 or 0.5 g/kg) for 7, 14 or 21 days and after these periods, one-hour venous thrombosis model was performed. Control group received 0.9 % NaCl solution and was sham operated. The statistical significance of results was computed by Mann – Whitney’s test. We observed that thrombus weight was decreased in animals obtaining WPC-8080 and that was statistically significant in 14 and 21-day supplemented groups. Blood count parameters did not differ significantly in rats with and without thrombosis induction whether they were fed with WPC-80 or not. Moreover, the number of platelets (PLT) was within the normal range in each group. The examined coagulation parameters in rats of the control groups were within normal limits. After WPC-80 supplementation there was the tendency to prolonged activated partial thromboplastin time (aPTT), but in comparison, the results did not turn out significant. In animals that received WPC-80 0.3 g·kg-1 for 21 days with and without induced thrombosis, prothrombin time (PT) and an international normalized ratio (INR) was somewhat decreased, remaining within the normal range, but the nature and significance of this observation are beyond the framework of the current study. Additionally, fibrinogen and thrombin time (TT) did not differ significantly between groups. Therefore the exact effect of WPC-80 on coagulation system is still elusive and requires further thorough research including mechanisms of action. Determining the potential clinical application of WPC-80 requires the selection of the optimal dose and duration of supplementation.Keywords: antithrombotic, rats, venous thrombosis, WPC-80
Procedia PDF Downloads 112244 Vortex Flows under Effects of Buoyant-Thermocapillary Convection
Authors: Malika Imoula, Rachid Saci, Renee Gatignol
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A numerical investigation is carried out to analyze vortex flows in a free surface cylinder, driven by the independent rotation and differentially heated boundaries. As a basic uncontrolled isothermal flow, we consider configurations which exhibit steady axisymmetric toroidal type vortices which occur at the free surface; under given rates of the bottom disk uniform rotation and for selected aspect ratios of the enclosure. In the isothermal case, we show that sidewall differential rotation constitutes an effective kinematic means of flow control: the reverse flow regions may be suppressed under very weak co-rotation rates, while an enhancement of the vortex patterns is remarked under weak counter-rotation. However, in this latter case, high rates of counter-rotation reduce considerably the strength of the meridian flow and cause its confinement to a narrow layer on the bottom disk, while the remaining bulk flow is diffusion dominated and controlled by the sidewall rotation. The main control parameters in this case are the rotational Reynolds number, the cavity aspect ratio and the rotation rate ratio defined. Then, the study proceeded to consider the sensitivity of the vortex pattern, within the Boussinesq approximation, to a small temperature gradient set between the ambient fluid and an axial thin rod mounted on the cavity axis. Two additional parameters are introduced; namely, the Richardson number Ri and the Marangoni number Ma (or the thermocapillary Reynolds number). Results revealed that reducing the rod length induces the formation of on-axis bubbles instead of toroidal structures. Besides, the stagnation characteristics are significantly altered under the combined effects of buoyant-thermocapillary convection. Buoyancy, induced under sufficiently high Ri, was shown to predominate over the thermocapillay motion; causing the enhancement (suppression) of breakdown when the rod is warmer (cooler) than the ambient fluid. However, over small ranges of Ri, the sensitivity of the flow to surface tension gradients was clearly evidenced and results showed its full control over the occurrence and location of breakdown. In particular, detailed timewise evolution of the flow indicated that weak thermocapillary motion was sufficient to prevent the formation of toroidal patterns. These latter detach from the surface and undergo considerable size reduction while moving towards the bulk flow before vanishing. Further calculations revealed that the pattern reappears with increasing time as steady bubble type on the rod. However, in the absence of the central rod and also in the case of small rod length l, the flow evolved into steady state without any breakdown.Keywords: buoyancy, cylinder, surface tension, toroidal vortex
Procedia PDF Downloads 351243 Effective Apixaban Clearance with Cytosorb Extracorporeal Hemoadsorption
Authors: Klazina T. Havinga, Hilde R. H. de Geus
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Introduction: Pre-operative coagulation management of Apixaban prescribed patients, a new oral anticoagulant (a factor Xa inhibitor), is difficult, especially when chronic kidney disease (CKD) causes drug overdose. Apixaban is not dialyzable due to its high level of protein binding. An antidote, Andexanet α, is available but expensive and has an unfavorable short half-life. We report the successful extracorporeal removal of Apixaban prior to emergency surgery with the CytoSorb® Hemoadsorption device. Methods: A 89-year-old woman with CKD, with an Apixaban prescription for atrial fibrillation, was presented at the ER with traumatic rib fractures, a flail chest, and an unstable spinal fracture (T12) for which emergency surgery was indicated. However, due to very high Apixaban levels, this surgery had to be postponed. Based on the Apixaban-specific anti-factor Xa activity (AFXaA) measurements at admission and 10 hours later, complete clearance was expected after 48 hours. In order to enhance the Apixaban removal and reduce the time to operation, and therefore reduce pulmonary complications, CRRT with CytoSorb® cartridge was initiated. Apixaban-specific anti-factor Xa activity (AFXaA) was measured frequently as a substitute for Apixaban drug concentrations, pre- and post adsorber, in order to calculate the adsorber-related clearance. Results: The admission AFXaA concentration, as a substitute for Apixaban drug levels, was 218 ng/ml, which decreased to 157 ng/ml after ten hours. Due to sustained anticoagulation effects, surgery was again postponed. However, the AFXaA levels decreased quickly to sub-therapeutic levels after CRRT (Multifiltrate Pro, Fresenius Medical Care, Blood flow 200 ml/min, Dialysate Flow 4000 ml/h, Prescribed renal dose 51 ml-kg-h) with Cytosorb® connected in series into the circuit was initiated (within 5 hours). The adsorber-related (indirect) Apixaban clearance was calculated every half hour (Cl=Qe * (AFXaA pre- AFXaA post/ AFXaA pre) with Qe=plasma flow rate calculated with Ht=0.38 and system blood flow rate 200 ml-min): 100 ml/min, 72 ml/min and 57 ml/min. Although, as expected, the adsorber-related clearance decreased quickly due to saturation of the beads, still the reduction rate achieved resulted in a very rapid decrease in AFXaA levels. Surgery was ordered and possible within 5 hours after Cytosorb initiation. Conclusion: The CytoSorb® Hemoadsorption device enabled rapid correction of Apixaban associated anticoagulation.Keywords: Apixaban, CytoSorb, emergency surgery, Hemoadsorption
Procedia PDF Downloads 144