Search results for: in-utero drug exposure
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3883

Search results for: in-utero drug exposure

2263 Evaluation of Antioxidant and Anticancer Activity of Tinospora cordifolia against Ehrlich Ascites Carcinoma: In Vitro, in vivo and in silico Approach

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

Abstract:

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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2262 Adverse Childhood Experience of Domestic Violence and Domestic Mental Health Leading to Youth Violence: An Analysis of Selected Boroughs in London

Authors: Sandra Smart-Akande, Chaminda Hewage, Imtiaz Khan, Thanuja Mallikarachchi

Abstract:

According to UK police-recorded data, there has been a substantial increase in knife-related crime and youth violence in the UK since 2014 particularly in the London boroughs. These crime rates are disproportionally distributed across London with the majority of these crimes occurring in the highly deprived areas of London and among young people aged 11 to 24 with large discrepancies across ethnicity, age, gender and borough of residence. Comprehensive studies and literature have identified risk factors associated with a knife carrying among youth to be Adverse Childhood Experience (ACEs), poor mental health, school or social exclusion, drug dealing, drug using, victim of violent crime, bullying, peer pressure or gang involvement, just to mention a few. ACEs are potentially traumatic events that occur in childhood, this can be experiences or stressful events in the early life of a child and can lead to an increased risk of damaging health or social outcomes in the latter life of the individual. Research has shown that children or youths involved in youth violence have had childhood experience characterised by disproportionate adverse childhood experiences and substantial literature link ACEs to be associated with criminal or delinquent behavior. ACEs are commonly grouped by researchers into: Abuse (Physical, Verbal, Sexual), Neglect (Physical, Emotional) and Household adversities (Mental Illness, Incarcerated relative, Domestic violence, Parental Separation or Bereavement). To the author's best knowledge, no study to date has investigated how household mental health (mental health of a parent or mental health of a child) and domestic violence (domestic violence on a parent or domestic violence on a child) is related to knife homicides across the local authorities areas of London. This study seeks to address the gap by examining a large sample of data from the London Metropolitan Police Force and Characteristics of Children in Need data from the UK Department for Education. The aim of this review is to identify and synthesise evidence from data and a range of literature to identify the relationship between adverse childhood experiences and youth violence in the UK. Understanding the link between ACEs and future outcomes can support preventative action.

Keywords: adverse childhood experiences, domestic violence, mental health, youth violence, prediction analysis, London knife crime

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2261 Functionalization of Carboxylated Single-Walled Carbon Nanotubes with 2-En 4-Hydroxy Cyclo 1-Octanon and Toxicity Investigation

Authors: D. ChobfroushKhoei, S. K. Heidari , Sh. Dariadel

Abstract:

Carbon nanotubes were used in medical sciences especially in drug delivery system and cancer therapy. In this study, we functionalized carboxylated single-wall carbon nanotubes (SWNT-COOH) with 2-en 4-hydroxy cyclo 1-octanon. Synthesized sample was characterized by FT-IR, Raman spectroscopy, SEM, TGA and cellular investigations. The results showed well formation of SWNT-Ester. Cell viability assay results and microscopic observations demonstrated that cancerous cells were killed in the sample. The synthesized sample can be used as a toxic material for cancer therapy.

Keywords: MWNT-COOH, functionalization, phenylisocyanate, phenylisothiocyanate, 1, 4-phenylendiamine, toxicity investigation

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2260 Condensed Benzo, Pyrido, Pyrimidino-Imidazole Derivatives as Antidiabetic Agents

Authors: Fatima Doganc, Hakan Goker

Abstract:

Benzimidazole moiety is an important pharmacophore and privileged structure for the medicinal chemists, since it exhibits various important biological activities. Some clinically used drugs have benzimidazole moiety, such as omeprazole, astemizole, albendazole and domperidone. 2-(4-tert-Butylphenyl)benzimidazole, is a PGC-1α transcriptional regulator shown to have beneficial effects in diabetic mice. We planned to modify the structure of this compound for developing new antidiabetic drug candidates. Hence, a series of guanidino or amidino, benzo/pyrido/pyrimidino-imidazole derivatives were freshly prepared. Mass, 1H-NMR, 13C-NMR, 2D-NMR spectroscopy techniques were used for the new derivatives to clarify their structures and their purity was controlled through the elemental analysis. Antidiabetic activity studies of the synthesized compounds are under the investigation.

Keywords: antidiabetic agents, benzimidazole, imidazopyridine, imidazopyrimidine

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2259 Using SNAP and RADTRAD to Establish the Analysis Model for Maanshan PWR Plant

Authors: J. R. Wang, H. C. Chen, C. Shih, S. W. Chen, J. H. Yang, Y. Chiang

Abstract:

In this study, we focus on the establishment of the analysis model for Maanshan PWR nuclear power plant (NPP) by using RADTRAD and SNAP codes with the FSAR, manuals, and other data. In order to evaluate the cumulative dose at the Exclusion Area Boundary (EAB) and Low Population Zone (LPZ) outer boundary, Maanshan NPP RADTRAD/SNAP model was used to perform the analysis of the DBA LOCA case. The analysis results of RADTRAD were similar to FSAR data. These analysis results were lower than the failure criteria of 10 CFR 100.11 (a total radiation dose to the whole body, 250 mSv; a total radiation dose to the thyroid from iodine exposure, 3000 mSv).

Keywords: RADionuclide, transport, removal, and dose estimation (RADTRAD), symbolic nuclear analysis package (SNAP), dose, PWR

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2258 Ethylene Sensitivity in Orchids and Its Control Using 1-MCP: A Review

Authors: Parviz Almasi

Abstract:

Ethylene is produced as a gaseous growth regulator in all plants and their constructive parts such as roots, stems, leaves, flowers and fruits. It is considered a multifunctional phytohormone that regulates both growths including flowering, fruit ripening, inhibition of root growth, and senescence such as senescence of leaves and flowers and etc. In addition, exposure to external ethylene is caused some changes that are often undesirable and harmful. Some flowers are more sensitive to others and when exposed to ethylene; their aging process is hastened. 1-MCP is an exogenous and endogenous ethylene action inhibitor, which binds to the ethylene receptors in the plants and prevents ethylene-dependent reactions. The binding affinity of 1- MCP for the receptors is about 10 times more than ethylene. Hence, 1-MCP can be a potential candidate for controlling of ethylene injury in horticultural crops. This review integrates knowledge of ethylene biosynthesis in the plants and also a mode of action of 1-MCP in preventing of ethylene injury.

Keywords: ethylene injury, biosynthesis, ethylene sensitivity, 1-MCP

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2257 Radiation Effects in the PVDF/Graphene Oxide Nanocomposites

Authors: Juliana V. Pereira, Adriana S. M. Batista, Jefferson P. Nascimento, Clascídia A. Furtado, Luiz O. Faria

Abstract:

Exposure to ionizing radiation has been found to induce changes in poly(vinylidene fluoride) (PVDF) homopolymers. The high dose gamma irradiation process induces the formation of C=C and C=O bonds in its [CH2-CF2]n main chain. The irradiation also provokes crosslinking and chain scission. All these radio-induced defects lead to changes in the PVDF crystalline structure. As a consequence, it is common to observe a decrease in the melting temperature (TM) and melting latent heat (LM) and some changes in its ferroelectric features. We have investigated the possibility of preparing nanocomposites of PVDF with graphene oxide (GO) through the radio-induction of molecular bonds. In this work, we discuss how the gamma radiation interacts with the nanocomposite crystalline structure.

Keywords: gamma irradiation, graphene oxide, nanocomposites, PVDF

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2256 Aloe vera Prevents Injuries Induced by Whole Body X-ray Irradiation in Rodents

Authors: Shashi Bala, Neha A. Chugh, Subhash C. Bansal, Mohal L. Garg, Ashwani Koul

Abstract:

Purpose: The present study was designed to evaluate the radioprotective efficacy of Aloe vera from whole body X-ray exposure in rodents. Materials and Methods: For this purpose, after on week’s acclimatization, male balb/c mice procured from Central Animal House, Panjab University, Chandigarh (India), were divided into four groups: Group I mice served as control. Group II mice were orally administrated Aloe vera pulp extract (50 mg/ kg body weight) on alternate days for 30 days. Group III mice were subjected to whole body X-ray irradiation to cumulative dose of 2Gy (0.258Gy twice a day for four days in the last week). Group IV animals were pretreated with Aloe vera pulp extract on alternate days as in Group II and in the last week of the study, they were exposed to X-ray as in Group III. Results: Spleen of X-ray irradiated mice showed histopathological alterations accompanied with enhanced activity of lactate dehydrogenase (LDH) in serum. Elevated levels of reactive oxygen species (ROS), lipid peroxidation (LPO), enhanced activities in Glutathione based enzymes such as Glutathione peroxidase (GSH-Px), Glutathione reductase (GR), Catalase (CAT), Superoxide dismutase (SOD) associated with depletion in reduced Glutathione (GSH) concentration were observed after X-ray exposure in blood plasma and spleen.. Pro-inflammatory cytokines like tumor necrosis factors (TNF-α) and Inteleukin-6 (IL-6) levels were also found to be enhanced in serum of irradiated mice. Irradiation-induced significant elevation in Total leucocyte counts (TLC), neutrophil counts and decline in platelet counts, associated with unaltered levels of red blood cell counts (RBC’s) and haemoglobin (Hb) in various treatment groups. Clastogenic damage and apoptosis was also found to be increase in splenic tissue of X-ray exposed mice as assessed by micronucleus and TUNEL assay. However, X-ray irradiated animals administered with Aloe vera revealed significant improvement in levels of ROS/ LPO, LDH activity, and antioxidant mechanism. Aloe vera pretreated animals exhibited less severe damage, and early recovery in micronucleated cells, hematological parameters, apoptotic cells and inflammatory markers as compared to X-ray exposed mice. Conclusion: These results indicate that the radioprotective potential of Aloe vera against X-ray induced damage. This may be due to its free radical scavenging, antioxidant, anti-apoptotic and anti-inflammatory properties.

Keywords: aloe vera, antioxidant defense system, lactate dehydrogenase (LDH), micronucleus assay, x-ray

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2255 Identification of Peroxisome Proliferator-Activated Receptors α/γ Dual Agonists for Treatment of Metabolic Disorders, Insilico Screening, and Molecular Dynamics Simulation

Authors: Virendra Nath, Vipin Kumar

Abstract:

Background: TypeII Diabetes mellitus is a foremost health problem worldwide, predisposing to increased mortality and morbidity. Undesirable effects of the current medications have prompted the researcher to develop more potential drug(s) against the disease. The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptors family and take part in a vital role in the regulation of metabolic equilibrium. They can induce or repress genes associated with adipogenesis, lipid, and glucose metabolism. Aims: Investigation of PPARα/γ agonistic hits were screened by hierarchical virtual screening followed by molecular dynamics simulation and knowledge-based structure-activity relation (SAR) analysis using approved PPAR α/γ dual agonist. Methods: The PPARα/γ agonistic activity of compounds was searched by using Maestro through structure-based virtual screening and molecular dynamics (MD) simulation application. Virtual screening of nuclear-receptor ligands was done, and the binding modes with protein-ligand interactions of newer entity(s) were investigated. Further, binding energy prediction, Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit along with the structural comparative analysis of approved PPARα/γ agonists with screened hit was done for knowledge-based SAR. Results and Discussion: The silicone chip-based approach recognized the most capable nine hits and had better predictive binding energy as compared to the reference drug compound (Tesaglitazar). In this study, the key amino acid residues of binding pockets of both targets PPARα/γ were acknowledged as essential and were found to be associated in the key interactions with the most potential dual hit (ChemDiv-3269-0443). Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit and found root mean square deviation (RMSD) stabile around 2Å and 2.1Å, respectively. Frequency distribution data also revealed that the key residues of both proteins showed maximum contacts with a potent hit during the MD simulation of 20 nanoseconds (ns). The knowledge-based SAR studies of PPARα/γ agonists were studied using 2D structures of approved drugs like aleglitazar, tesaglitazar, etc. for successful designing and synthesis of compounds PPARγ agonistic candidates with anti-hyperlipidimic potential.

Keywords: computational, diabetes, PPAR, simulation

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2254 Acute Myocardial Infarction Associated with Ingestion of Herbal Mixtures Containing Acetylcholinesterase Inhibitors: A Case Study

Authors: M. Hakami, A. Jammaly, I. Attafi, M. Oraiby, M. Jeraiby

Abstract:

We reviewed an unusual case of a 65-year-old male taking an herbal mixture containing compounds with anticholinesterase activity for a long period of time, presented with acute my myocardial infarction and multiple organ dysfunction syndrome followed by death. Clinically, there are findings correlated with anticholinesterase activity, such as bilateral miosis, diaphoresis, vomiting and fasciculation without a history of any toxic ingestion or exposure. Gas chromatography–mass spectrometry screening studies identified the presence of thymol, anethole in the herbal extract and butylated hydroxytoluene in the blood sample. Hence, with this case report, we intend to highlight the necessity of evaluating the long-term use of the herbal mixture.

Keywords: cholinesterase inhibitors, thymole, anethole, butylatedhydroxytoluene, cardiac toxicity, myocardial infarction

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2253 Household Climate-Resilience Index Development for the Health Sector in Tanzania: Use of Demographic and Health Surveys Data Linked with Remote Sensing

Authors: Heribert R. Kaijage, Samuel N. A. Codjoe, Simon H. D. Mamuya, Mangi J. Ezekiel

Abstract:

There is strong evidence that climate has changed significantly affecting various sectors including public health. The recommended feasible solution is adopting development trajectories which combine both mitigation and adaptation measures for improving resilience pathways. This approach demands a consideration for complex interactions between climate and social-ecological systems. While other sectors such as agriculture and water have developed climate resilience indices, the public health sector in Tanzania is still lagging behind. The aim of this study was to find out how can we use Demographic and Health Surveys (DHS) linked with Remote Sensing (RS) technology and metrological information as tools to inform climate change resilient development and evaluation for the health sector. Methodological review was conducted whereby a number of studies were content analyzed to find appropriate indicators and indices for climate resilience household and their integration approach. These indicators were critically reviewed, listed, filtered and their sources determined. Preliminary identification and ranking of indicators were conducted using participatory approach of pairwise weighting by selected national stakeholders from meeting/conferences on human health and climate change sciences in Tanzania. DHS datasets were retrieved from Measure Evaluation project, processed and critically analyzed for possible climate change indicators. Other sources for indicators of climate change exposure were also identified. For the purpose of preliminary reporting, operationalization of selected indicators was discussed to produce methodological approach to be used in resilience comparative analysis study. It was found that household climate resilient index depends on the combination of three indices namely Household Adaptive and Mitigation Capacity (HC), Household Health Sensitivity (HHS) and Household Exposure Status (HES). It was also found that, DHS alone cannot complement resilient evaluation unless integrated with other data sources notably flooding data as a measure of vulnerability, remote sensing image of Normalized Vegetation Index (NDVI) and Metrological data (deviation from rainfall pattern). It can be concluded that if these indices retrieved from DHS data sets are computed and scientifically integrated can produce single climate resilience index and resilience maps could be generated at different spatial and time scales to enhance targeted interventions for climate resilient development and evaluations. However, further studies are need to test for the sensitivity of index in resilience comparative analysis among selected regions.

Keywords: climate change, resilience, remote sensing, demographic and health surveys

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2252 Novel EGFR Ectodomain Mutations and Resistance to Anti-EGFR and Radiation Therapy in H&N Cancer

Authors: Markus Bredel, Sindhu Nair, Hoa Q. Trummell, Rajani Rajbhandari, Christopher D. Willey, Lewis Z. Shi, Zhuo Zhang, William J. Placzek, James A. Bonner

Abstract:

Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligand-independent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.

Keywords: head and neck cancer, EGFR mutation, resistance, cetuximab

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2251 Fuzzy Optimization for Identifying Anticancer Targets in Genome-Scale Metabolic Models of Colon Cancer

Authors: Feng-Sheng Wang, Chao-Ting Cheng

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Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

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2250 Antiulcer Potential of Heme Oxygenase-1 Inducers

Authors: Gaweł Magdalena, Lipkowska Anna, Olbert Magdalena, Frąckiewicz Ewelina, Librowski Tadeusz, Nowak Gabriel, Pilc Andrzej

Abstract:

Heme oxygenase-1 (HO-1), also known as heat shock protein 32 (HSP32), has been shown to be implicated in cytoprotection in various organs. Its activation plays a significant role in acute and chronic inflammation, protecting cells from oxidative injury and apoptosis. This inducible isoform of HO catalyzes the first and rate-limiting step in heme degradation to produce equimolar quantities of biologically active products: carbon monoxide (CO), free iron and biliverdin. CO has been reported to possess anti-apoptotic properties. Moreover, it inhibits the production of proinflammatory cytokines and stimulates the synthesis of the anti-inflammatory interleukin-10 (IL-10), as well as promotes vasodilatation at sites of inflammation. The second product of catalytic HO-1 activity, free cytotoxic iron, is promptly sequestered into the iron storage protein ferritin, which lowers the pro-oxidant state of the cell. The third product, biliverdin, is subsequently converted by biliverdin reductase into the bile pigment bilirubin, the most potent endogenous antioxidant among the constituents of human serum, which modulates immune effector functions and suppresses inflammatory response. Furthermore, being one of the so-called stress proteins, HO-1 adaptively responds to different stressors, such as reactive oxygen species (ROS), inflammatory cytokines and heavy metals and thus protects cells against such conditions as ischemia, hemorrhagic shock, heat shock or hypoxia. It is suggested that pharmacologic modulation of HO-1 may represent an effective strategy for prevention of stress and drug-induced gastrointestinal toxicity. HO-1 is constitutively expressed in normal gastric, intestinal and colonic mucosa and up-regulated during inflammation. It has been proven that HO-1 up-regulated by hemin, heme and cobalt-protoporphyrin ameliorates experimental colitis. In addition, the up-regulation of HO-1 partially explains the mechanism of action of 5-aminosalicylic acid (5-ASA), which is used clinically as an anti-colitis agent. In 2009 Ueda et al. has reported for the first time that mucosal protection by Polaprezinc, a chelate compound of zinc and L-carnosine used as an anti-ulcer drug in Japan, is also attributed to induction of HO-1 in the stomach. Since then, inducers of HO-1 are desired subject of research, as they may constitute therapeutically effective anti-ulcer drugs.

Keywords: heme oxygenase-1, gastric lesions, gastroprotection, Polaprezinc

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2249 [Keynote Talk]: Bioactive Cyclic Dipeptides of Microbial Origin in Discovery of Cytokine Inhibitors

Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan

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Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.

Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha

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2248 The Impact of Technology on Cultural Heritage among Preschool Children

Authors: Adenike Akinrotimi

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Globally, education has been identified as vital tool for any form of development for any society (community); be it economic, social, political and cultural development. It is the determinant level of prosperity, welfare, security and sustenance of the people of a particular community. Education could be formal, informal and non-formal. Cultural development of an individual and of the community as it were is a lifelong process, where individual learns from daily experiences, exposure to the environment at home, at work, at play and it enriches human and environmental potentials. This type of education can be referred to as cultural heritage. It is built on learner participation and assimilation. Preschool programme also referred to as Early Childhood Education is critical to holistic development of a child cultural development inclusive. This paper examines the impact that technology has on cultural heritage among preschool children.

Keywords: cultural heritage, education, pre-school, technology

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2247 Pharmacy-Station Mobile Application

Authors: Taissir Fekih Romdhane

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This paper proposes a mobile web application named Pharmacy-Station that sells medicines and permits user to search for medications based on their symptoms, making it is easy to locate a specific drug online without the need to visit a pharmacy where it may be out of stock. This application is developed using the jQuery Mobile framework, which uses many web technologies and languages such as HTML5, PHP, JavaScript and CSS3. To test the proposed application, we used data from popular pharmacies in Saudi Arabia that included important information such as location, contact, and medicines in stock, etc. This document describes the different steps followed to create the Pharmacy-Station application along with screenshots. Finally, based on the results, the paper concludes with recommendations and further works planned to improve the Pharmacy-Station mobile application.

Keywords: pharmacy, mobile application, jquery mobile framework, search, medicine

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2246 The Effect of Peer Pressure and Leisure Boredom on Substance Use Among Adolescents in Low-Income Communities in Capetown

Authors: Gaironeesa Hendricks, Shazly Savahl, Maria Florence

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The aim of the study is to determine whether peer pressure and leisure boredom influence substance use among adolescents in low-income communities in Cape Town. Non-probability sampling was used to select 296 adolescents between the ages of 16–18 from schools located in two low-income communities. The measurement tools included the Drug Use Disorders Identification Test, the Resistance to Peer Influence and Leisure Boredom Scales. Multiple regression revealed that the combined influence of peer pressure and leisure boredom predicted substance use, while peer pressure emerged as a stronger predictor than leisure boredom on substance use among adolescents.

Keywords: substance use, peer pressure, leisure boredom, adolescents, multiple regression

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2245 A General Strategy for Noise Assessment in Open Mining Industries

Authors: Diego Mauricio Murillo Gomez, Enney Leon Gonzalez Ramirez, Hugo Piedrahita, Jairo Yate

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This paper proposes a methodology for the management of noise in open mining industries based on an integral concept, which takes into consideration occupational and environmental noise as a whole. The approach relies on the characterization of sources, the combination of several measurements’ techniques and the use of acoustic prediction software. A discussion about the difference between frequently used acoustic indicators such as Leq and LAV is carried out, aiming to establish common ground for homologation. The results show that the correct integration of this data not only allows for a more robust technical analysis but also for a more strategic route of intervention as several departments of the company are working together. Noise control measurements can be designed to provide a healthy acoustic surrounding in which the exposure workers but also the outdoor community is benefited.

Keywords: environmental noise, noise control, occupational noise, open mining

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2244 The Hypoglycaemic and Antioxidant Effects of Ethanolic Extract of Curcuma Longa Rhizomes Alone and with Two Pepper Adjuvants in Alloxan-Induced Diabetic Rats

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

Abstract:

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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2243 Tool Development for Assessing Antineoplastic Drugs Surface Contamination in Healthcare Services and Other Workplaces

Authors: Benoit Atge, Alice Dhersin, Oscar Da Silva Cacao, Beatrice Martinez, Dominique Ducint, Catherine Verdun-Esquer, Isabelle Baldi, Mathieu Molimard, Antoine Villa, Mireille Canal-Raffin

Abstract:

Introduction: Healthcare workers' exposure to antineoplastic drugs (AD) is a burning issue for occupational medicine practitioners. Biological monitoring of occupational exposure (BMOE) is an essential tool for assessing AD contamination of healthcare workers. In addition to BMOE, surface sampling is a useful tool in order to understand how workers get contaminated, to identify sources of environmental contamination, to verify the effectiveness of surface decontamination way and to ensure monitoring of these surfaces. The objective of this work was to develop a complete tool including a kit for surface sampling and a quantification analytical method for AD traces detection. The development was realized with the three following criteria: the kit capacity to sample in every professional environment (healthcare services, veterinaries, etc.), the detection of very low AD traces with a validated analytical method and the easiness of the sampling kit use regardless of the person in charge of sampling. Material and method: AD mostly used in term of quantity and frequency have been identified by an analysis of the literature and consumptions of different hospitals, veterinary services, and home care settings. The kind of adsorbent device, surface moistening solution and mix of solvents for the extraction of AD from the adsorbent device have been tested for a maximal yield. The AD quantification was achieved by an ultra high-performance liquid chromatography method coupled with tandem mass spectrometry (UHPLC-MS/MS). Results: With their high frequencies of use and their good reflect of the diverse activities through healthcare, 15 AD (cyclophosphamide, ifosfamide, doxorubicin, daunorubicin, epirubicin, 5-FU, dacarbazin, etoposide, pemetrexed, vincristine, cytarabine, methothrexate, paclitaxel, gemcitabine, mitomycin C) were selected. The analytical method was optimized and adapted to obtain high sensitivity with very low limits of quantification (25 to 5000ng/mL), equivalent or lowest that those previously published (for 13/15 AD). The sampling kit is easy to use, provided with a didactic support (online video and protocol paper). It showed its effectiveness without inter-individual variation (n=5/person; n= 5 persons; p=0,85; ANOVA) regardless of the person in charge of sampling. Conclusion: This validated tool (sampling kit + analytical method) is very sensitive, easy to use and very didactic in order to control the chemical risk brought by AD. Moreover, BMOE permits a focal prevention. Used in routine, this tool is available for every intervention of occupational health.

Keywords: surface contamination, sampling kit, analytical method, sensitivity

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2242 Comparison of the Use of Vaccines or Drugs against Parasitic Diseases

Authors: H. Al-Khalaifa, A. Al-Nasser

Abstract:

The viewpoint towards the use of drugs or vaccines against avian parasitic diseases is one of the most striking challenges in avian medical parasitology. This includes many difficulties associated with drug resistance and in developing prophylactic vaccines. In many instances, the potential success of a vaccination in controlling parasitic diseases in poultry is well-documented. However, some medical, technical and financial limitations are still paramount. On the other hand, chemotherapy is not very well-recommended due to a number of medical limitations. But in the absence of an effective vaccine, drugs are used against parasitic diseases. This paper sheds light on some the advantages and disadvantages of using vaccination and drugs in controlling parasitic diseases in poultry species. The usage of chemotherapeutic drugs is discussed with some examples. Then, more light will be shed on using vaccines as a potentially effective and promising control tool.

Keywords: drugs, parasitology, poultry, vaccines

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2241 Development and Validation of a Green Analytical Method for the Analysis of Daptomycin Injectable by Fourier-Transform Infrared Spectroscopy (FTIR)

Authors: Eliane G. Tótoli, Hérida Regina N. Salgado

Abstract:

Daptomycin is an important antimicrobial agent used in clinical practice nowadays, since it is very active against some Gram-positive bacteria that are particularly challenges for the medicine, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). The importance of environmental preservation has receiving special attention since last years. Considering the evident need to protect the natural environment and the introduction of strict quality requirements regarding analytical procedures used in pharmaceutical analysis, the industries must seek environmentally friendly alternatives in relation to the analytical methods and other processes that they follow in their routine. In view of these factors, green analytical chemistry is prevalent and encouraged nowadays. In this context, infrared spectroscopy stands out. This is a method that does not use organic solvents and, although it is formally accepted for the identification of individual compounds, also allows the quantitation of substances. Considering that there are few green analytical methods described in literature for the analysis of daptomycin, the aim of this work was the development and validation of a green analytical method for the quantification of this drug in lyophilized powder for injectable solution, by Fourier-transform infrared spectroscopy (FT-IR). Method: Translucent potassium bromide pellets containing predetermined amounts of the drug were prepared and subjected to spectrophotometric analysis in the mid-infrared region. After obtaining the infrared spectrum and with the assistance of the IR Solution software, quantitative analysis was carried out in the spectral region between 1575 and 1700 cm-1, related to a carbonyl band of the daptomycin molecule, and this band had its height analyzed in terms of absorbance. The method was validated according to ICH guidelines regarding linearity, precision (repeatability and intermediate precision), accuracy and robustness. Results and discussion: The method showed to be linear (r = 0.9999), precise (RSD% < 2.0), accurate and robust, over a concentration range from 0.2 to 0.6 mg/pellet. In addition, this technique does not use organic solvents, which is one great advantage over the most common analytical methods. This fact contributes to minimize the generation of organic solvent waste by the industry and thereby reduces the impact of its activities on the environment. Conclusion: The validated method proved to be adequate to quantify daptomycin in lyophilized powder for injectable solution and can be used for its routine analysis in quality control. In addition, the proposed method is environmentally friendly, which is in line with the global trend.

Keywords: daptomycin, Fourier-transform infrared spectroscopy, green analytical chemistry, quality control, spectrometry in IR region

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2240 Chronic Toxicity of Halofenozide on a Larvivorous Fish, Gambusia affinis: Acetylcholinesterase, Glutathione S-transferase Activities and Glutathione

Authors: Chouahda Salima, Soltani Noureddine

Abstract:

The present study is a part of biological control against mosquitoes. It aims to assess the impact of a selective insect growth regulator: halofenozide in mosquitofish: Gambusia affinis. Acetylcholinesterase (AChE), glutathione S-transferase (GST) and glutathione (GSH) used in assessing of environmental stress were measured in juveniles and adults males and females. The response of these biomarkers reveals an inhibition of AChE specific activity, an induction of GST activity, and decrease of GSH rates in juveniles in the end of experiment and during chronic treatment adult males and females. The effect of these biomarkers is more pronounced in females compared to males and juveniles. These different biomarkers have a similar profile for the duration of exposure.

Keywords: biomarkers, chronic toxicity, insecticide, halofenozide, Gambusia affinis, pollution

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2239 A Comparative Approach for Modeling the Toxicity of Metal Mixtures in Two Ecologically Related Three-Spined (Gasterosteus aculeatus L.) And Nine-Spined (Pungitius pungitius L.) Sticklebacks

Authors: Tomas Makaras

Abstract:

Sticklebacks (Gasterosteiformes) are increasingly used in ecological and evolutionary research and become well-established role as model species for biologists. However, ecotoxicology studies concerning behavioural effects in sticklebacks regarding stress responses, mainly induced by chemical mixtures, have hardly been addressed. Moreover, although many authors in their studies emphasised the similarity between three-spined and nine-spined stickleback in morphological, neuroanatomical and behavioural adaptations to environmental changes, several comparative studies have revealed considerable differences between these species in and their susceptibility and resistance to variousstressors in laboratory experiments. The hypothesis of this study was that three-spined and nine-spined stickleback species will demonstrate apparent differences in response patterns and sensitivity to metal-based chemicals stimuli. For this purpose, we investigated the swimming behaviour (including mortality rate based on 96-h LC50 values) of two ecologically similar three-spined (Gasterosteusaculeatus) and nine-spined sticklebacks (Pungitiuspungitius) to short-term (up to 24 h) metal mixture (MIX) exposure. We evaluated the relevance and efficacy of behavioural responses of test species in the early toxicity assessment of chemical mixtures. Fish exposed to six (Zn, Pb, Cd, Cu, Ni and Cr) metals in the mixture were either singled out by the Water Framework Directive as priority or as relevant substances in surface water, which was prepared according to the environmental quality standards (EQSs) of these metals set for inland waters in the European Union (EU) (Directive 2013/39/EU). Based on acute toxicity results, G. aculeatus found to be slightly (1.4-fold) more tolerant of MIX impact than those of P. pungitius specimens. The performed behavioural analysis showed the main effect on the interaction between time, species and treatment variables. Although both species exposed to MIX revealed a decreasing tendency in swimming activity, these species’ responsiveness to MIX was somewhat different. Substantial changes in the activity of G. aculeatus were established after 3-h exposure to MIX solutions, which was 1.43-fold lower, while in the case of P. pungitius, 1.96-fold higher than established 96-h LC50 values for each species. This study demonstrated species-specific differences in response sensitivity to metal-based water pollution, indicating behavioural insensitivity of P. pungitiuscompared to G. aculeatus. While many studies highlight the usefulness and suitability of nine-spined sticklebacks for evolutionary and ecological research, attested by their increasing popularity in these fields, great caution must be exercised when using them as model species in ecotoxicological research to probe metal contamination. Meanwhile, G. aculeatus showed to be a promising bioindicator species in the environmental ecotoxicology field.

Keywords: acute toxicity, comparative behaviour, metal mixture, swimming activity

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2238 The New Propensity Score Method and Assessment of Propensity Score: A Simulation Study

Authors: Azam Najafkouchak, David Todem, Dorothy Pathak, Pramod Pathak, Joseph Gardiner

Abstract:

Propensity score (PS) methods have recently become the standard analysis tool for causal inference in observational studies where exposure is not randomly assigned. Thus, confounding can impact the estimation of treatment effect on the outcome. Due to the dangers of discretizing continuous variables, the focus of this paper will be on how the variation in cut-points or boundaries will affect the average treatment effect utilizing the stratification of the PS method. In this study, we will develop a new methodology to improve the efficiency of the PS analysis through stratification and simulation study. We will also explore the property of empirical distribution of average treatment effect theoretically, including asymptotic distribution, variance estimation and 95% confident Intervals.

Keywords: propensity score, stratification, emprical distribution, average treatment effect

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2237 Refractory Visceral Leishmaniasis Responding to Second-Line Therapy

Authors: Preet Shah, Om Shrivastav

Abstract:

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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2236 The Investigation of Effect of Alpha Lipoic Acid against Damage on Neonatal Rat Lung to Maternal Tobacco Smoke Exposure

Authors: Elif Erdem, Nalan Kaya, Gonca Ozan, Durrin Ozlem Dabak, Enver Ozan

Abstract:

This study was carried out to determine the histological and biochemical changes in the lungs of the rat pups exposed to tobacco smoke during pregnancy period and to investigate the protective effects of alpha lipoic acid, which is administered during pregnancy, on these changes. In our study, 24 six-week old Spraque-Dawley female rats weighing 160 ± 10 g were used (n:7). Rats were randomly divided into four equal groups: group I (control), group II (tobacco smoke), group III (tobacco smoke + alpha lipoic acid) and group IV (alpha lipoic acid). Rats in the group II, group III were exposed to tobacco smoke twice a day for one hour starting from eight weeks before mating and during pregnancy. In addition to tobacco smoke, 20 mg/kg of alpha lipoic acid was administered via oral gavage to the rats in the group III. Only alpha lipoic acid was administered to the rats in the group IV. Once after the delivery, all administrations were stopped. On the 7 and 21th days, the seven pups of all groups were decapitated. A portion of the lung was taken and stained with HE, PAS and Masson. In addition to immunohistochemical staining of surfactant protein A, vascular endothelial growth factor, caspase-3, TUNEL method was also used to determine apoptosis. Biochemical analyzes were performed with some part of the lung tissue specimens. In the histological evaluations performed under light microscopy, inflammatory cell increase, hemorrhagic areas, edema, interalveolar septal thickening, alveolar numbers decrease, degeneration of some bronchi and bronchial epithelium, epithelial cells that were fallen into the lumen and hyaline membrane formation were observed in tobacco smoke group. These findings were ameliorated in tobacco smoke + ALA group. Hyaline membrane formation was not detected in this group. The TUNEL positive cell numbers a significant increase was detected in the tobacco smoke group, whereas a significant decrease was detected in the tobacco smoke + ALA group. In terms of the immunoreactivity of both SP-A and VEGF, a significant decrease was observed in the tobacco smoke group, and a significant increase was observed in the tobacco smoke + ALA group. Regarding the immunoreactivity of caspase-3, there was a significant increase in the group of tobacco smoke and a significant decrease in the group of tobacco smoke + ALA. The malondialdehyde levels were determined to be significantly increased in the tobacco smoke group, and a significant decreased in the tobacco smoke + ALA. Glutathione and superoxide dismutase enzyme activities showed a significant decrease in the group of tobacco smoke and a significant increase in the tobacco smoke + ALA group. In conclusion, we suggest that the exposure to tobacco smoke during pregnancy leads to morphological, histopathological and functional changes on lung development by causing oxidative damage in lung tissues of neonatal rats and the maternal use of alpha lipoic acid can provide a protective effect on the neonatal lung development against this oxidative stress originating from tobacco smoke.

Keywords: alpha lipoic acid, lung, neonate, tobacco smoke, pregnancy

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2235 Conservative and Surgical Treatment of Antiresorptive Drug-Related Osteonecrosis of the Jaw with Ultrasonic Piezoelectric Bone Surgery under Polyvinylpyrrolidone Iodine Irrigation: A Case Series of 13 Treated Sites

Authors: Esra Yuce, Isil D. S. Yamaner, Murude Yazan

Abstract:

Aims and objective: Antiresorptive agents including bisphosphonates and denosumab as strong suppressors of osteoclasts are the most commonly used antiresorptive medications for the treatment of osteoporosis which counteract the negative quantitative alteration of trabecular and cortical bone by inhibition of bone turnover. Oral bisphosphonate therapy for the treatment of osteopenia, osteoporosis or Paget's disease is associated with the low-grade risk of osteonecrosis of the jaw, while higher-grade risk is associated with receiving intravenous bisphosphonates therapy in the treatment of multiple myeloma and bone metastases. On the other hand, there has been a remarkable increase in incidences of antiresorptive related osteonecrosis of the jaw (ARONJ) in oral bisphosphonate users. This clinical presentation will evaluate the healing outcomes via piezoelectric bone surgery under the irrigation of PVP-I solution irrigation in patients received bisphosphonate therapy. Material-Method: The study involved 8 female and 5 male patients that have been treated for ARONJ. Among 13 necrotic sites, 9 were in the mandible and 4 were in the maxilla. All of these 13 patients treated with surgical debridement via piezoelectric bone surgery under irrigation by solution with 3% PVP-I concentration in combination with long-term antibiotic therapy and 5 also underwent removal of mobile segments of bony sequestrum. All removable prosthesis in 8 patients were relined with soft liners during the healing periods in order to eliminate chronic minor traumas. Results: All patients were on oral bisphosphonate therapy for at least 2 years and 5 of which had received intravenous bisphosphonates up to 1 year before therapy with oral bisphosphonates was started. According to the AAOMS staging system, four cases were stage II, eight cases were stage I, and one case was stage III. The majority of lesions were identified at sites of dental prostheses (38%) and dental extractions (62%). All patients diagnosed with ARONJ stage I had used unadjusted removable prostheses. No recurrence of the symptoms was observed during the present follow-up (9–37 months). Conclusion: Despite their confirmed effectiveness, the prevention and treatment of osteonecrosis of the jaw secondary to oral bisphosphonate therapy remain major medical challenges. Treatment with piezoelectric bone surgery with irrigation of povidone-iodine solution was effective for management of bisphosphonate-related osteonecrosis of the jaw. Taking precautions for patients treated with oral bisphosphonates, especially also denture users, may allow for a reduction in the rate of developing osteonecrosis of the maxillofacial region.

Keywords: antiresorptive drug related osteonecrosis, bisphosphonate therapy, piezoelectric bone surgery, povidone iodine

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2234 The Effect of Disseminating Basic Knowledge on Radiation in Emergency Distance Learning of COVID-19

Authors: Satoko Yamasaki, Hiromi Kawasaki, Kotomi Yamashita, Susumu Fukita, Kei Sounai

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People are susceptible to rumors when the cause of their health problems is unknown or invisible. In order for individuals to be unaffected by rumors, they need basic knowledge and correct information. Community health nursing classes use cases where basic knowledge of radiation can be utilized on a regular basis, thereby teaching that basic knowledge is important in preventing anxiety caused by rumors. Nursing students need to learn that preventive activities are essential for public health nursing care. This is the same methodology used to reduce COVID-19 anxiety among individuals. This study verifies the learning effect concerning the basic knowledge of radiation necessary for case consultation by emergency distance learning. Sixty third-year nursing college students agreed to participate in this research. The knowledge tests conducted before and after classes were compared, with the chi-square test used for testing. There were five knowledge questions regarding distance lessons. This was considered to be 5% significant. The students’ reports which describe the results of responding to health consultations, were analyzed qualitatively and descriptively. In this case study, a person living in an area not affected by radiation was anxious about drinking water and, thus, consulted with a student. The contents of the lecture were selected the minimum amount of knowledge used for the answers of the consultant; specifically hot spots, internal exposure risk, food safety, characteristics of cesium-137, and precautions for counselors. Before taking the class, the most correctly answered question by students concerned daily behavior at risk of internal exposure (52.2%). The question with the fewest correct answers was the selection of places that are likely to be hot spots (3.4%). All responses increased significantly after taking the class (p < 0.001). The answers to the counselors, as written by the students, were 'Cesium is strongly bound to the soil, so it is difficult to transfer to water' and 'Water quality test results of tap water are posted on the city's website.' These were concrete answers obtained by using specialized knowledge. Even in emergency distance learning, the students gained basic knowledge regarding radiation and created a document to utilize said knowledge while assuming the situation concretely. It was thought that the flipped classroom method, even if conducted remotely, could maintain students' learning. It was thought that setting specific knowledge and scenes to be used would enhance the learning effect. By changing the case to concern that of the anxiety caused by infectious diseases, students may be able to effectively gain the basic knowledge to decrease the anxiety of residents due to infectious diseases.

Keywords: effect of class, emergency distance learning, nursing student, radiation

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