Search results for: cancer drug

Authors: Suzanne Overstreet-Juenke

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Disproportionate minority contact (DMC) is a salient issue that has been found at every stage of the decision-making process in the juvenile justice system. Existing research indicates that DMC influences adjudication for drug, property, and personal crimes. Because intimate partner violence (IPV) is a major public health problem and global concern, the current study examines DMC at adjudication among youth charged for crimes of interpersonal violence. This research uses administrative, Court Designated Worker (CDW) data collected from 2014 to 2016. The results are contextualized using Steffensmeier’s version of focal concerns theory of judicial decision-making. This study assesses race and two seriousness of offense measures to establish whether a link exists between race and adjudication. The results of the study is similar to prior research on the topic. These results are discussed in terms of policy implications, limitations, and future research.

Keywords: race, disproportionate minority contact, focal concerns theory, juvenile

Procedia PDF Downloads 71

Authors: Naomi Seidu, Edward Poluyi, Chibuikem Ikwuegbuenyi, Eghosa Morgan

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The current poor prognosis of glioblastoma has called for the need for an improvement in treatment methods in order to improve its survival rate. Despite the different interventions currently available for this tumor, the average survival is still only a few months. (12-15). The aim is to create a more favorable prognosis and have a reduction in the resistance to treatment currently being experienced, even with surgical interventions and chemotherapy. From the available literature, there is a relationship between the presence of HOX genes (Homeobox genes) and glioblastoma, which could be attributable to the increasing treatment resistance. Hence silencing these genes can be a key to improving survival rates of glioblastoma. A series of studies have highlighted the role that HOX genes play in glioblastoma prognosis. Promotion of human glioblastoma initiation, aggressiveness, and resistance to Temozolomide has been associated with HOXA9. The role of HOX gene expression in cancer stem cells should be studied as it could provide a means of designing CSC-targeted therapies, as CSCs play a part in the initiation and progression of solid tumors.

Keywords: GBM- glioblastoma, HOXA gene- homeobox genes cluster, signaling pathways, temozolomide

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Authors: S. K. Hemalata, M. N. Shiva Kameshwari

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The present work focusses on anti-inflammatory action of Urginea wightii in-vitro. Urginea wightii is a member of Hyacinthaceae and considered to be wonder plant because of its varied important medicinal properties. The plant is endemic to India, Africa, and Mediterranian regions. Presence of alkaloids, flavonoid-glycosides especially flavonone derivatives are responsible for the strong anti-inflammatory activity of Urginea wightii. In present research work, anti-inflammatory activity of methanol extract of the bulb powder was tested on Male Wistar Rats. In these test animals, inflammation was induced by injecting carrageenan as the irritant to induce paw edema in Wistar rats. Inflammation of Paw edema was treated with both plant extract and Pyrox gel a known synthetic anti-inflammatory drug through external application. The result indicated that anti-inflammatory activity of Urginea wightii extract was almost similar to the synthetic Pyrox gel. This disproves the modern world's scepticism towards the herbal medicines and encourages to rely on natural plant extracts.

Keywords: anti-inflammatory activity, flavonoid-glycosides, Pyrox gel, Urginia wightii

Procedia PDF Downloads 162

Authors: M. Koksal, T. Ozyazici, E. Gurdal, M. Yarım, E. Demirpolat, M. B. Y. Aycan

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The discovery of new drugs in cancer chemotherapy is still a major topic because of severe side effects, selectivity problems and resistance development potential of existing drugs. In recent years, combined anticancer therapies or multi-acting drugs are clinically preferred over traditional cytotoxic treatment, with the aim of avoiding resistance and toxic side effects. Arrangement of multi-acting targets can be carried out either by combination of several drugs with different mechanisms or by usage of a single chemical compound capable of regulating several targets of a disease with multiple factors. In literature, several pyrimidine and piperazine derivatives have been involved in the structure of many compounds which have been used as chemotherapeutic agents along with wide clinical applications. The aim of this study is to combine pyrimidine and piperazine core structures to research and develop novel piperazinylpyrimidine derivatives with selective cytotoxicity over cancer cells. In this study, a group of novel 6-fluorophenyl-3-[2-(substitutedpiperazinyl)ethyl] hexahydropyrimidine-2,4-dione derivatives designed to observe the desired anticancer activity due to pyrimidine and piperazine based scaffolds. Target compounds were obtained by the reaction of appropriate piperazine derivatives and 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione. The synthetic pathway of 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione was started with Rodionov reaction using aldehyde, malonic acid and ammonium acetate in ethanol. Isolated β-fluorophenyl-β-amino acids were treated with 2-chloroethylisocyanate in the presence of an aqueous sodium hydroxide solution at room temperature to yield the sodium salts of the corresponding ureido acids. By addition of a mineral acid, ureido acids were precipitated. Later, these ureido acids were refluxed in thionyl chloride to give the 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-di-one which were furthermore treated with secondary amines. Structures of purified compounds were characterized with IR, 1H-NMR, 13C-NMR, mass spectroscopies and elemental analysis. All of the compounds gave satisfactory analytical and spectroscopic data, which were in full accordance with their depicted structures. In IR spectra of the compounds, N-H group was seen at 3230-3213 cm⁻¹. C-H was seen at 3100-2820 cm⁻¹ and C=O vibrational peaks were observed approximately at 1725 and 1665 cm⁻¹ in accordance with literature. In the NMR spectra of target compounds, the methylene protons of piperazine give two separate multiplet peaks around 3.5 and 4.5 ppm representing the successful N-alkylation of the structure. The cytotoxic activity of the synthesized compounds was investigated on human bronchial epithelial (BEAS 2B), lung (A549), colon adenocarcinoma (COLO205) and breast (MCF7) cell lines, by means of sulphorhodamine B (SRB) assays in triplicate. IC₅₀ values of the screened derivatives were found in range of 11.8-78 µM. This project was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 215S157).

Keywords: cytotoxicity, hexahydropyrimidine, piperazine, sulphorhodamine B assay

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Authors: Doyin Afolabi, Phillip Adewole, Oladipupo Sennaike

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Most well-known classifiers, including the decision tree algorithm, can make predictions on balanced datasets efficiently. However, the decision tree algorithm tends to be biased towards imbalanced datasets because of the skewness of the distribution of such datasets. To overcome this problem, this study proposes a weighted decision tree algorithm that aims to remove the bias toward the majority class and prevents the reduction of majority observations in imbalance datasets classification. The proposed weighted decision tree algorithm was tested on three imbalanced datasets- cancer dataset, german credit dataset, and banknote dataset. The specificity, sensitivity, and accuracy metrics were used to evaluate the performance of the proposed decision tree algorithm on the datasets. The evaluation results show that for some of the weights of our proposed decision tree, the specificity, sensitivity, and accuracy metrics gave better results compared to that of the ID3 decision tree and decision tree induced with minority entropy for all three datasets.

Keywords: data mining, decision tree, classification, imbalance dataset

Procedia PDF Downloads 125

Authors: Liang Zhou, Xiaojing Zhu, Yin Lu

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Danshen can induce the angiogenesis in advanced ischemic heart disease while inhibiting the angiogenesis in cancer. Additionally, Danshen mainly contains two groups of ingredients: the hydrophilic phenolic acids (danshensu, caffeic acid and salvianolic acid B), and the lipophilic tanshinones (dihydrotanshinone I, tanshinone II A, and cryptotanshinone). The lipophilic tanshinones reduced the VEGF- and bFGF-induced proliferation of HUVECs in dose-dependent manner, but cannot perform in others. Conversely, caffeic acid and salvianolic acid B had the opposite effect. Danshensu inhibited the VEGF- and bFGF-induced migration of HUVECs, and others were not. Most of them interrupted the forming capillary-like structures of HUVECs, except the danshensu and caffeic acid. Oppositely, caffeic acid enhanced the ability of forming capillary-like structures of HUVECs. Ultimately, the lipophilic tanshinones, danshensu and salvianolic acid B inhibited the angiogenesis, whereas the caffeic acid induced the angiogenesis. These data provide useful information for the classification of ingredients of Danshen for angiogenesis.

Keywords: angiogenesis, Danshen, HUVECs, ingredients

Procedia PDF Downloads 385

Authors: K. Menad, A. Feddag, M. A. Hassnaoui

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We are living in a time and in a world heavily polluted. In the list of the great dangers awaiting the man can be placed on top of the list pollution by heavy metals: lead, mercury, cadmium, etc. Fatigue, Depression, Thyroid disorder, Alzheimer's, Parkinson's, Cancer, are some of the health problems caused by heavy metal pollution. The environmental protection has long since become a major political and economic issue. Among the priorities, include safeguarding water resources. All countries of the world are concerned either because they lack water or because they pollute it. There are several ways to remove these heavy metals; ion exchange by zeolites is one of these ways, which our work is based on. Zeolites were among the main clean up materials by either adsorption, ion exchange and catalysis. Lead and cadmium, heavy metals, is one of the main dangers fulminate the flora and fauna of our small planet, so many resources are deployed to remedy them. The elimination of lead and cadmium by ion exchange has been extensively studied. However, exchange capacity of more and larger formed a major challenge for researchers and industry.

Keywords: composite, ion excahnge, zeolite LTA, zeolite x

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Authors: D. Benmoussa, H. Hannache, O. Cherkaoui

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In textiles, the major interest in microencapsulation is currently in the application of durable fragrances, skin softeners, phase-change materials, antimicrobial agents and drug delivery systems onto textile materials. In our research “Polyethylene Glycol” was applied as phase change material and it was encapsulated in polymethacrylic acid (PMA) by radical polymerization in suspension of methacrylic acid in presence of N,N'-methylenebisacrylamide (MBAM) as crosslinking agent. Thereafter the obtained microcapsule was modified by amidation with ethylenediamine as a spacer molecule. At the end of this spacer trichlorotriazine reactive group was fixed. Microcapsules were grafted onto cotton textile substrate. The surface morphologies of the microencapsulated phase change materials (micro PCMs) were studied by scanning electron microscopy (SEM). Thermal properties, thermal reliabilities and thermal stabilities of the as-prepared micro PCMs were investigated by differential scanning calorimetry (DSC) and thermogravmetric analysis (TGA). The results obtained show the obtaining microcapsules with a mean diameter of 10 µm and the resistance of the microcapsules is demonstrated by thermal analysis.

Keywords: energy storage, microencapsulation, phase-change materials, thermogravmetric analysis (TGA)

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Authors: Michaela Chovancova, Pavel Niedoba

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For the treatment of acute and chronic lung diseases it is preferred to deliver medicaments by inhalation. The drug is delivered directly to tracheobronchial tree. This way allows the given medicament to get directly into the place of action and it makes rapid onset of action and maximum efficiency. The transport of aerosol particles in the particular part of the lung is influenced by their size, anatomy of the lungs, breathing pattern and airway resistance. This article deals with calculation of airway resistance in the lung model of Horsfield. It solves the problem of determination of the pressure losses in bifurcation and thus defines the pressure drop at a given location in the bronchial tree. The obtained data will be used as boundary conditions for transport of aerosol particles in a central part of bronchial tree realized by Computational Fluid Dynamics (CFD) approach. The results obtained from CFD simulation will allow us to provide information on the required particle size and optimal inhalation technique for particle transport into particular part of the lung.

Keywords: human lungs, bronchial tree, pressure losses, airways resistance, flow, breathing

Procedia PDF Downloads 354

Authors: J. Ticona Chambi, E. A. De Almeida, C. A. Andrade Raymundo Gaiotto, A. M. Do Espírito Santo, L. Infantes, S. L. Cuffini

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The solubility of active pharmaceutical ingredients (APIs) is challenging for the pharmaceutical industry. The new multicomponent crystalline forms as cocrystal and solvates present an opportunity to improve the solubility of APIs. Commonly, the procedure to obtain multicomponent crystalline forms of a drug starts by screening the drug molecule with the different coformers/solvents. However, it is necessary to develop methods to obtain multicomponent forms in an efficient way and with the least possible environmental impact. The Hansen Solubility Parameters (HSPs) is considered a tool to obtain theoretical knowledge of the solubility of the target compound in the chosen solvent. H-Bond Propensity (HBP), Molecular Complementarity (MC), Coordination Values (CV) are tools used for statistical prediction of cocrystals developed by the Cambridge Crystallographic Data Center (CCDC). The HSPs and the CCDC tools are based on inter- and intra-molecular interactions. The curcumin (Cur), target molecule, is commonly used as an anti‐inflammatory. The demethoxycurcumin (Demcur) and bisdemethoxycurcumin (Bisdcur) are natural analogues of Cur from turmeric. Those target molecules have differences in their solubilities. In this way, the work aimed to analyze and compare different tools for multicomponent forms prediction (solvates) of Cur, Demcur and Biscur. The HSP values were calculated for Cur, Demcur, and Biscur using the chemical group contribution methods and the statistical optimization from experimental data. The HSPmol software was used. From the HSPs of the target molecules and fifty solvents (listed in the HSP books), the relative energy difference (RED) was determined. The probability of the target molecules would be interacting with the solvent molecule was determined using the CCDC tools. A dataset of fifty molecules of different organic solvents was ranked for each prediction method and by a consensus ranking of different combinations: HSP, CV, HBP and MC values. Based on the prediction, 15 solvents were selected as Dimethyl Sulfoxide (DMSO), Tetrahydrofuran (THF), Acetonitrile (ACN), 1,4-Dioxane (DOX) and others. In a starting analysis, the slow evaporation technique from 50°C at room temperature and 4°C was used to obtain solvates. The single crystals were collected by using a Bruker D8 Venture diffractometer, detector Photon100. The data processing and crystal structure determination were performed using APEX3 and Olex2-1.5 software. According to the results, the HSPs (theoretical and optimized) and the Hansen solubility sphere for Cur, Demcur and Biscur were obtained. With respect to prediction analyses, a way to evaluate the predicting method was through the ranking and the consensus ranking position of solvates already reported in the literature. It was observed that the combination of HSP-CV obtained the best results when compared to the other methods. Furthermore, as a result of solvent selected, six new solvates, Cur-DOX, Cur-DMSO, Bicur-DOX, Bircur-THF, Demcur-DOX, Demcur-ACN and a new Biscur hydrate, were obtained. Crystal structures were determined for Cur-DOX, Biscur-DOX, Demcur-DOX and Bicur-Water. Moreover, the unit-cell parameter information for Cur-DMSO, Biscur-THF and Demcur-ACN were obtained. The preliminary results showed that the prediction method is showing a promising strategy to evaluate the possibility of forming multicomponent. It is currently working on obtaining multicomponent single crystals.

Keywords: curcumin, HSPs, prediction, solvates, solubility

Procedia PDF Downloads 56

Authors: M. Zehtabian, Z. Molaiemanesh, Z. Shafahi, M. Papie, M. Zahraie Moghaddam, M. Mehralizadeh, M. R. Vahidi, S. Sina

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The introduction of CT scans has been a great improvement in diagnosis of different diseases. However, this imaging modality can expose the patients to cumulative radiation doses which may increase the risks of some health problems like cancer. In this study, the dose delivered to different organs in lumbar-abdominal imaging was measured by putting the TLD-100, and TLD-100H chips inside the Alderson Rando phantom. The lumbar-abdominal image of the phantom was obtained, while TLD chips were inside the holes of the phantom. According to the results obtained in this study using TLD-100 chips, the average dose received by liver, bladder, rectum, kidneys, and uterus were found to be 12.9 mSv, 8.9 mSv, 10.1 mSv, 11.0 mSv, 11.2 mSv, and 10.5 mSv respectively, while the measurements performed by TLD-100H show that the average dose to liver, bladder, rectum, kidneys, and uterus were found to be 12.4 mSv, 9.2 mSv, 9.5 mSv, 10.5 mSv, 10.7 mSv, and 9.9 mSv respectively. The results of this study indicates that the dose measured by the TLD-100H chips are in close agreement with those obtained by TLD-100.

Keywords: CT scan, dose, TLD-100, diagnosis

Procedia PDF Downloads 626

Authors: Meitham Amereh, Mohsen Akbari, Ben Nadler

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Cancer has been recognized as one of the most challenging problems in biology and medicine. Aggressive tumors are a lethal type of cancers characterized by high genomic instability, rapid progression, invasiveness, and therapeutic resistance. Their behavior involves complicated molecular biology and consequential dynamics. Although tremendous effort has been devoted to developing therapeutic approaches, there is still a huge need for new insights into the dark aspects of tumors. As one of the key requirements in better understanding the complex behavior of tumors, mathematical modeling and continuum physics, in particular, play a pivotal role. Mathematical modeling can provide a quantitative prediction on biological processes and help interpret complicated physiological interactions in tumors microenvironment. The pathophysiology of aggressive tumors is strongly affected by the extracellular cues such as stresses produced by mechanical forces between the tumor and the host tissue. During the tumor progression, the growing mass displaces the surrounding extracellular matrix (ECM), and due to the level of tissue stiffness, stress accumulates inside the tumor. The produced stress can influence the tumor by breaking adherent junctions. During this process, the tumor stops the rapid proliferation and begins to remodel its shape to preserve the homeostatic equilibrium state. To reach this, the tumor, in turn, upregulates epithelial to mesenchymal transit-inducing transcription factors (EMT-TFs). These EMT-TFs are involved in various signaling cascades, which are often associated with tumor invasiveness and malignancy. In this work, we modeled the tumor as a growing hyperplastic mass and investigated the effects of mechanical stress from surrounding ECM on tumor invasion. The invasion is modeled as volume-preserving inelastic evolution. In this framework, principal balance laws are considered for tumor mass, linear momentum, and diffusion of nutrients. Also, mechanical interactions between the tumor and ECM is modeled using Ciarlet constitutive strain energy function, and dissipation inequality is utilized to model the volumetric growth rate. System parameters, such as rate of nutrient uptake and cell proliferation, are obtained experimentally. To validate the model, human Glioblastoma multiforme (hGBM) tumor spheroids were incorporated inside Matrigel/Alginate composite hydrogel and was injected into a microfluidic chip to mimic the tumor’s natural microenvironment. The invasion structure was analyzed by imaging the spheroid over time. Also, the expression of transcriptional factors involved in invasion was measured by immune-staining the tumor. The volumetric growth, stress distribution, and inelastic evolution of tumors were predicted by the model. Results showed that the level of invasion is in direct correlation with the level of predicted stress within the tumor. Moreover, the invasion length measured by fluorescent imaging was shown to be related to the inelastic evolution of tumors obtained by the model.

Keywords: cancer, invasion, mathematical modeling, microfluidic chip, tumor spheroids

Procedia PDF Downloads 106

Authors: Nantawan Soonklang, Linda Chularojanamontri, Urarat Nanna

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Ethnopharmacological relevance: Thunbergia laurifolia Lindl. belongs to the family Acanthaceae commonly known as Rang jeud in Thailand. This plant is traditionally used in Thailand for centuries as an antidote for several poisons and drug overdose. Aim of the study: This research aimed to study the analgesic and antipyretic activities of T. laurifolia water extract by using animal models. Materials and Methods: The analgesic activity was studied using 2 methods of pain induction including acetic acid and heat induced pain. And the antipyretic activity study was performed by yeast-induced hyperthermia. Results: The results showed that the administration of T. laurifolia extract possessed analgesic activity by reducing acetic acid-induced writhing response and heat-induced pain as well as showed antipyretic activity by decreasing body temperature of hyperthermic rats induced by brewer’s yeast. Conclusion: The study indicates that the T. laurifolia extract possesses analgesic and antipyretic activities in animals.

Keywords: Thunbergia laurifolia extract, analgesic activity, antipyretic activity, hyperthermia

Procedia PDF Downloads 384

Authors: Sangbok Lee

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There has been much effort on process improvement for outpatient clinics to provide quality and acute care to patients. One of the efforts is no-show analysis or prediction. This work analyzes patient no-shows along with patient health conditions. The health conditions refer to clinical symptoms that each patient has, out of the followings; hyperlipidemia, diabetes, metastatic solid tumor, dementia, chronic obstructive pulmonary disease, hypertension, coronary artery disease, myocardial infraction, congestive heart failure, atrial fibrillation, stroke, drug dependence abuse, schizophrenia, major depression, and pain. A dataset from a regional hospital is used to find the relationship between the number of the symptoms and no-show probabilities. Additional analysis reveals how each symptom or combination of symptoms affects no-shows. In the above analyses, cross-classification of patients by age and gender is carried out. The findings from the analysis will be used to take extra care to patients with particular health conditions. They will be forced to visit clinics by being informed about their health conditions and possible consequences more clearly. Moreover, this work will be used in the preparation of making institutional guidelines for patient reminder systems.

Keywords: healthcare system, no show analysis, process improvment, statistical data analysis

Procedia PDF Downloads 231

Authors: Raquel Dafouz Neus Cáceres, Javier Fernandez-Rubio, Belinda Huerta José Luis Rodríguez-Gil, Nicola Mastroianni, Miren López de Alda, Damià Barceló, Yolanda Valcárcel

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The region of Galicia, found in north-western (NW) Spain, is a national and world leader in shellfish, especially mussel production, and recognized for its fishing industry. Few studies have evaluated the presence of emerging contaminants in NW Spain, with those published mainly concerning the continental aquatic environment. The objective of this study was to identify the environmental risk posed by the presence of pharmaceuticals and drugs of abuse in this important coastal region. The presence of sixteen pharmaceuticals (benzodiazepines, anxiolytics, and caffeine), and 19 drugs of abuse (cocainics, amphetamine-like compounds, opiates and opioids, lysergic compounds, and cannabinoids) was assessed in 23 sites located in the Rías (Coastal inlets) of Muros, Arousa, and Pontevedra (NW Spain). Twenty-two of these locations were affected by waste-water treatment plant (WWTP) effluents, and one represented the effluent of one of these WWTPs. Venlafaxine was the pharmaceutical compound detected at higher concentration in the three Rías, with a maximum value of 291 ng/L at the site Porto do Son (Ría de Muros). Total concentration in the three Rías was 819,26 ng/L. Next, citalopram and lorazepam were the most prevalent compounds detected. Metabolite of cocaine benzoylecgonine was the drug of abuse with the highest concentration, measured at 972 ng/L in the Ría of Noia WWTP (no dilution). This compound was also detected at 142 ng/L in the site La Isla de Aros, Ría of Pontevedra. Total concentration for the three Rías was 1210 ng/L. Ephedrine was also detected at high level in the three Rías, with a total concentration of 579,28 ng/L. The results obtained for caffeine show maximum and average concentrations of 857 ng/L Isla de Arosa, Ría de Pontevedra the highest measured in seawater in Spain. A preliminary hazard assessment was carried out by comparing these measured environmental concentrations (MEC) to predicted no-effect concentrations (PNECs) for aquatic organisms. Six out of the 22 seawater samples resulted in a Hazard Quotient (HQ) from chronic exposure higher than 1 with the highest being 17.14, indicating a high probability of adverse effects in the aquatic environment. In addition, the risk was assessed on the basis of persistence, bioaccumulation, and toxicity (PBT). This work was financially supported by the Spanish Ministry of Economy and Competitiveness through the Carlos III Health Institute and the program 'Proyectos de Investigacion en Salud 2015-2017' FIS (PI14/00516), the European Regional Development Fund (ERDF), the Catalan Government (Consolidated Research Groups '2014 SGR 418 - Water and Soil Quality Unit' and 2014 SGR 291 - ICRA), and the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 603437. The poster entitled 'Environmental Risk of Pharmaceuticals, Drugs of Abuse and Stimulant Caffeine in Marine Water: A Case Study in the North-Western of Spain'.

Keywords: drug of abuse, pharmaceuticals, caffeine, environmental risk, seawater

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Authors: Siao-Wei Jiang, Boy-Young Hsieh, Ching-Liang Hsieh, Cheng-Yung Lin

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The problems of multiple drug resistance in the pig farming industry have been emphasized in recent years. Diarrhea syndrome is common in weaning piglets and often treated with antibiotics as a feed additive, leading to the rapid spread of antibiotic resistance and posing high health risks to humans. The study aimed to alleviate diarrhea syndrome with traditional herbal medicine, Xiang Sha Liu Jun Zi Tang, whose effects enhanced digestive function. Piglets at 4 weeks old with stool classified to Bristol stool classification type 6 or type 7 were randomly divided into the control group, group A (1% of Xiang Sha Liu Jun Zi Tang) and group B (0.1% Colistin). The piglets were administrated for 7 days, and their weight, feed intake, and stool score were recorded daily before and after the trial. The results showed that the diarrhea index score in group A and group B improved significantly compared to the control group, indicating that Xiang Sha Liu Jun Zi Tang may have the same effect on alleviating diarrhea syndrome as Colistin, and it may be another replacement for antibiotics.

Keywords: pig, diarrhea, herbal medicine, Xiang Sha Liu Jun Zi Tang

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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Authors: Fernando G. Torres, Omar P. Troncoso

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Starch is a highly biocompatible, non-toxic, and biodegradable polymer. It is widely used in biomedical applications, including drug delivery systems and tissue engineering scaffolds. Curcumin, a phenolic compound found in the dried root of Curcuma longa, has been used as a nutritional supplement due to its antimicrobial, anti-inflammatory, and antioxidant effects. However, the major problem with ingesting curcumin by itself is its poor bioavailability due to its poor absorption and rapid metabolism. In this study, we report a novel methodology to prepare starch nanoparticles loaded with curcumin. The nanoparticles were synthesized via nanoprecipitation of starch granules extracted from native Andean potatoes (Solanum tuberosum ssp. and Andigena var Huamantanga varieties). The nanoparticles were crosslinked and stabilized by using sodium tripolyphosphate and Tween®80, respectively. The characterization of the nanoparticles loaded with curcumin was assessed by Fourier Transform Infrared Spectroscopy, Dynamic Light Scattering, Zeta potential, and Differential scanning calorimetry. UV-vis spectrophotometry was used to evaluate the loading efficiency and capacity of the samples. The results showed that native starch nanoparticles could be used to prepare promising nanocarriers for the controlled release of curcumin.

Keywords: starch nanoparticle, nanoprecipitation, curcumin, biomedical applications

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Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri

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Dosimetry is an indispensable and precious factor in patient treatment planning to minimize the absorbed dose in vital tissues. In this study, compartmental model was used in order to estimate the human absorbed dose of ¹⁷⁷Lu-DOTATOC from the biodistribution data in wild type rats. For this purpose, ¹⁷⁷Lu-DOTATOC was prepared under optimized conditions and its biodistribution was studied in male Syrian rats up to 168 h. Compartmental model was applied to mathematical description of the drug behaviour in tissue at different times. Dosimetric estimation of the complex was performed using radiation absorbed dose assessment resource (RADAR). The biodistribution data showed high accumulation in the adrenal and pancreas as the major expression sites for somatostatin receptor (SSTR). While kidneys as the major route of excretion receive 0.037 mSv/MBq, pancreas and adrenal also obtain 0.039 and 0.028 mSv/MBq. Due to the usage of this method, the points of accumulated activity data were enhanced, and further information of tissues uptake was collected that it will be followed by high (or improved) precision in dosimetric calculations.

Keywords: compartmental modeling, human absorbed dose, ¹⁷⁷Lu-DOTATOC, Syrian rats

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Authors: Ziyad S. Haidar

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Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL), alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Opportunity: Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise and risk of immune reactions. For cases of dry sockets, specifically, the commercially-available and often-prescribed home remedies are highly lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Solution: Herein, SockGEL/PLUG (patent pending), an all-natural, drug-free and injectable stimuli-responsive hydrogel, was designed, formulated, characterized and evaluated as an osteogenic, angiogenic, anti-microbial and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in several oro-dental and cranio-maxillo-facial interventional applications; for example: in fresh dental extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (a) prevent the onset of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (b) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. Findings: The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physico-chemico-mechanically for safety (cell viability), viscosity, rheology, bio-distribution and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The performed animal model of cranial critical-sized and non-vascularized bone defects shall provide vitally critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease and speed in producing stable, biodegradable and sterilizable stimuli (thermo-sensitive and photo-responsive) matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for an intra-socket application, and beyond. Conclusions and Perspective: Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the bionanomaterial before engaging the market for feasibility, acceptance and cost-effectiveness studies. The SockGEL/PLUG platform is patent pending: SockGEL is a bio-inspired drug-free hydrogel; SockPLUG is a drug-loaded hydrogel designed for complex indications.

Keywords: hydrogel, injectable, dentistry, craniomaxillofacial complex, bioinspired, nanobiotechnology, biopolymer, sol-gel, stimuli-responsive, matrix, tissue engineering, regenerative medicine

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Authors: Palwinder Singh, Baljit Kaur, Sukhmeet Kaur

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Amongst a library of rationally designed small peptides, (H)Gly-Gly-Phe-Leu(OMe) was identified, reducing prostaglandin production of COX-2 with IC50 60 nM vs. 6000 nM for COX-1. The 5 mg Kg-1 dose of this compound rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of the compound for targeting COX-2, iNOS, and VGSC was investigated by using substances P, L-arginine, and veratrine, respectively, as the biomarkers. The interactions of the potent compound with COX-2 were supported by the isothermal calorimetry experiments showing Ka 6.10±1.10x104 mol-1 and ΔG -100.3 k J mol-1 in comparison to Ka 0.41x103 ±0.09 mol-1 and ΔG -19.2±0.06 k J mol-1 for COX-1. This compound did not show toxicity up to 2000 mg Kg-1 dose. Furthermore, beyond the conventional mode of working with anti-inflammatory agents through enzyme inhibition, COX-2 was provided with a peptide-based alternate substrate. Proline-centered pentapeptide iso-conformational to arachidonic acid exhibited appreciable selectivity for COX-2 overcoming acetic acid and formalin-induced pain in rats to almost 80% and was treated as a substrate by the enzyme. Hence, we suggest small peptides as highly potent and promising candidates for their further development into an anti-inflammatory drug.

Keywords: small peptides, cyclooxygenase, inflammation, substrate

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Authors: Payal Mazumdar, Sunita Rattan, Monalisa Mukherjee

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Polymer nanocomposites are a special class of materials having unique properties and wide application in diverse areas such as EMI shielding, sensors, photovoltaic cells, membrane separation properties, drug delivery etc. Recently the nanocomposites are being investigated for their use in biomedical fields as biosensors. Though nanocomposites with carbon nanoparticles have received worldwide attention in the past few years, comparatively less work has been done on nanographite although it has in-plane electrical, thermal and mechanical properties comparable to that of carbon nanotubes. The main challenge in the fabrication of these nanocomposites lies in the establishment of homogeneous dispersion of nanographite in polymer matrix. In the present work, attempts have been made to synthesize the nanocomposites of polystyrene and nanographite using click chemistry. The polymer and the nanographite are functionalized prior to the formation of nanocomposites. The polymer, polystyrene, was functionalized with alkyne moeity and nanographite with azide moiety. The fabricating of the nanocomposites was accomplished through click chemistry using Cu (I)-catalyzed Huisgen dipolar cycloaddition. The functionalization of filler and polymer was confirmed by NMR and FTIR. The nanocomposites formed by the click chemistry exhibit better electrical properties and the sensors are evaluated for their application as biosensors.

Keywords: nanocomposites, click chemistry, nanographite, biosensor

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Authors: Aneta Nitsch-Osuch, Damian Okrucinski, Magdalena Dawgialło, Izabela Gołębiak, Ernest Kuchar

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The Hospital Antibiotic Policy (HAP) should be implemented to rationalize the antibiotic use and to decrease the risk of spreading of spreading of resistant bacteria. The aim of our study was to describe the antibiotic consumption patterns at the single oncosurgery ward before and after implementation of the HAP. We conducted a retrospective analysis of the antibiotic use at the Oncosurgery Ward in Warsaw (Poland) in years 2011-2016. Calculations were based on daily defined doses (DDDs), DDDs/100 hospitalizations and DDDs/100 person-days, drug utilization rates (DU 90% and DU 100%) were also analysed. After implementation of the HAP, the total antibiotic consumption increased (365.35 DDD in 2011 vs. 1359,22 DDD in 2016). The significant change was observed in antibiotic consumption patterns: the use of amoxicillin clavulanate and carbapenems or glycopeptides decreased significantly (p < 0,05), while the use of ciprofloxacin and aminoglycosides increased (p < 0,05). The DU100% rate varied from 6 in 2011 to 12 in 2016; while DU 90% rate varied from 2 in 2011 to 3-5 in 2013-2016. Although the implementation of the HAP did not result in the decreased total antibiotic consumption, it provided favorable changes in the antibiotic consumption patterns.

Keywords: antibiotics, hospital, policy, stewardship

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Authors: Farah Ali, Tehreem Fiayyaz, Laeeq Akbar Lodhi, Imran Mirza

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The present work was undertaken to investigate effects of various extracts of W. somnifera (WS) for anti-diabetic activity in alloxan induced diabetic rabbits. Animals were divided into nine groups of six rabbits each. The animals of group 1 and 2 were given lactose (250 mg/kg, p.o) and WS root powder (100 mg/kg, p.o) respectively daily from day 1-20. Animals of group 3 were given alloxan (100 mg/kg, i.v) as a single dose on day 1. Powdered root of WS in the doses of 100, 150, 200 mg/kg and its aqueous (AWS) and ethanol extracts (EWS) (equivalent to 200 mg/kg of crude drug) were given to the treated animals (groups 4-8), respectively orally for three weeks (day 1-20 o.d), along with alloxan (100 mg/kg, i.v) as a single dose on day 1. Group 9 was given metformin (200 mg/kg) daily from day 1-20, along with a single dose of alloxan (100 mg/ kg, i.v) on day 1. Fasting serum glucose concentration in groups 3-9 was increased significantly (p<0.05) on day 3 as compared to normal control (NC) group (1). WS (100, 150, 200 mg/kg, p.o) decreased the fasting serum glucose concentration, with a maximum decrease (88.3 mg/dl) in group 2 (treated control) on day 21 of the experiment. These results indicate that metformin (reference control), (AWS) and (EWS) significantly antagonized the diabetic effects of alloxan.

Keywords: diabetes, serum, glucose, blood, sugar, rabbits

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Authors: Kathryn Watson

Abstract:

In 2020 North Carolina passed legislation mandating all educators be trained in identifying, referring, and supporting students showing signs of mental health issues, drug use, suicidal ideation, and sex trafficking. This study collected survey responses from 226 educators in North Carolina to better understand their perspectives on the legislation and their self-efficacy in supporting student mental health needs. Key findings of the study reveal that the mandated trainings increased educator awareness of student mental health, and higher awareness was linked to higher self-efficacy in supporting student mental health needs. Additionally, the results showed that educators who identify as Black had lower levels of self-efficacy in supporting student mental health. Additionally, rural educators were least likely to support the legislation in comparison to their urban and suburban counterparts. These findings can help inform policymakers in evaluating the policy and district decision-makers in selecting and implementing school-based mental health training.

Keywords: school-based mental health, education policy, student health, North Carolina, K-12 education

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Authors: Marcela Dvorakova, Lenka Langhansova, Premysl Landa

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A series of quinazoline derivatives bearing aromatic rings in 2- and 4-positions were prepared and tested for their biological activity. Firstly, the compounds were evaluated for their potential to inhibit various kinases, such as autophagy activating kinase ULK1, 3-Phosphoinositide-dependent kinase 1, and TANK-binding kinase 1. None of the compounds displayed any activity on these kinases. Secondly, the compounds were tested for their anti-inflammatory activity expressed as cyclooxygenase (COX) isoforms and 5-lipoxygenase (5-LOX) inhibition. Three of the compounds showed significant selectivity towards COX-1 isoform (COX-2/COX-1 SI = 20-30). They inhibited COX-1 in a single-digit µM range. There was also one compound that exhibited inhibitory activity towards all three tested enzymes in µM range (IC50COX-1 = 1.9 µM; IC50COX-2 and 5-LOX = 10.1µM. COX-1 inhibition was until recently considered undesirable due to COX-1 constitutive expression in most cell types and tissues. Thus, there are not many compounds known with selective COX-1 activity. However, it is now believed that COX-1 plays an important role in the pathophysiology of several acute and chronic disorders, including cancer or neurodegenerative diseases. Thus, the discovery of effective COX-1 selective inhibitors is desirable and important.

Keywords: cyclooxygenases, kinases, lipoxygenases, quinazolines

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Authors: Yaa Asuaba Duopah, Lisa Moran, Khalifa Elmusharaf, Dervla Kelly

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Background: Research has identified a strong link between stress and drug use behaviours. Also, it has been established that the prolonged use of crack cocaine stimulates emotional, cognitive, neurological, and social changes. This paper examines the psychosocial stressors associated with crack cocaine use. Methodology: The study is qualitative and adopts a critical realist approach. Data was collected through 26 face-to-face, in-depth, semi-structured interviews with people who use crack cocaine. Study participants were recruited through two addiction services using purposive. Participants consisted of 15 males and 11 females between the ages of 24-57 years. Data were analysed using thematic analysis. Results: Cravings, financial hardship, family breakdown, and emotional stimulation were revealed as psychosocial stressors associated with crack cocaine use. Conclusion: Addressing the psychosocial stressors identified in this paper through targeted interventions and supportive policies is crucial for improving the well-being of persons who use crack cocaine. Collaboration between addiction, mental health, and support services is recommended to develop and deliver these interventions.

Keywords: psychological stress, substance misuse disorder, mental health, coping

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Authors: Abdelhafid Zenati, Mohamed Tadjine

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The mathematical formulation of biomedical problems is an important phase to understand and predict the dynamic of the controlled population. In this paper we perform a stability analysis of a coupled model for healthy and cancerous cells dynamics in Acute Myeloid Leukemia, this represents our first aim. Second, we illustrate the effect of the interconnection between healthy and cancer cells. The PDE-based model is transformed to a nonlinear distributed state space model (delay system). For an equilibrium point of interest, necessary and sufficient conditions of global asymptotic stability are given. Thus, we came up to give necessary and sufficient conditions of global asymptotic stability of the origin and the healthy situation and control of the dynamics of normal hematopoietic stem cells and cancerous during myelode Acute leukemia. Simulation studies are given to illustrate the developed results.

Keywords: distributed delay, global stability, modelling, nonlinear models, PDE, state space

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Authors: Jan C. Droste, Justine Burns, Nithin Narayan

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Introduction: Life-threatening detrimental effects of inappropriate adrenaline (epinephrine) administration, e.g., by giving the wrong dose, in the context of anaphylaxis management is well documented in the medical literature. Half of the fatal anaphylactic reactions in the UK are iatrogenic, and the median time to a cardio-respiratory arrest can be as short as 5 minutes. It is therefore imperative that hospital doctors of all grades have active and accurate knowledge of the correct route, site, and dosage of administration of adrenaline. Given this time constraint and the potential fatal outcome with inappropriate management of anaphylaxis, it is alarming that surveys over the last 15 years have repeatedly shown only a minority of doctors to have accurate knowledge of adrenaline administration as recommended by the UK Resuscitation Council guidelines (2008 updated 2012). This comparison of survey results of the medical workforce over several years in a small NHS District General Hospital was conducted in order to establish the effect of the employment of multiple educational methods regarding adrenaline administration in anaphylaxis in adults. Methods: Between 2010 and 2017, several education methods and tools were used to repeatedly inform the medical workforce (doctors and advanced clinical practitioners) in a single district general hospital regarding the treatment of anaphylaxis in adults. Whilst the senior staff remained largely the same cohort, junior staff had changed fully in every survey. Examples included: (i) Formal teaching -in Grand Rounds; during the junior doctors’ induction process; advanced life support courses (ii) In-situ simulation training performed by the clinical skills simulation team –several ad hoc sessions and one 3-day event in 2017 visiting 16 separate clinical areas performing an acute anaphylaxis scenario using actors- around 100 individuals from multi-disciplinary teams were involved (iii) Hospital-wide distribution of the simulation event via the Trust’s Simulation Newsletter (iv) Laminated algorithms were attached to the 'crash trolleys' (v) A short email 'alert' was sent to all medical staff 3 weeks prior to the survey detailing the emergency treatment of anaphylaxis (vi) In addition, the performance of the surveys themselves represented a teaching opportunity when gaps in knowledge could be addressed. Face to face surveys were carried out in 2010 ('pre-intervention), 2015, and 2017, in the latter two occasions including advanced clinical practitioners (ACP). All surveys consisted of convenience samples. If verbal consent to conduct the survey was obtained, the medical practitioners' answers were recorded immediately on a data collection sheet. Results: There was a sustained improvement in the knowledge of the medical workforce from 2010 to 2017: Answers improved regarding correct drug by 11% (84%, 95%, and 95%); the correct route by 20% (76%, 90%, and 96%); correct site by 40% (43%, 83%, and 83%) and the correct dose by 45% (27%, 54%, and 72%). Overall, knowledge of all components -correct drug, route, site, and dose-improved from 13% in 2010 to 62% in 2017. Conclusion: This survey comparison shows knowledge of the medical workforce regarding adrenaline administration for treatment of anaphylaxis in adults can be considerably improved by employing a variety of educational methods.

Keywords: adrenaline, anaphylaxis, epinephrine, medical education, patient safety

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Authors: Amina Bayazid, Habiba Fetati, Houari Toumi

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Introduction: The clinical value of vitamin K antagonists (VKA) has been widely demonstrated in numerous indications. Unfortunately, VKA are not devoid of drawbacks and risk of serious bleeding. The iatrogenic induced by these drugs is a major public health problem. Patients & Methods: We conducted a retrospective study period extending from February 2012 to August 2013 in the pharmacovigilance service of EHUO (clinical pharmacology unit). The prescription of painkillers was analyzed in patients on VKA followed at our level. The influence of these analgesics on the evolution of the INR is an important component in our work. Results: We counted a total of 195 patients, of whom 32 (or 16.41% of the total population) had received analgesic treatment. The frequencies of different categories of analgesics administered were: • Analgesics opioids: 0% • Analgesics weak opioids: Tramadol: 21.87% • The non-opioid analgesics: -AINS: 71.87% (indomethacin: 68.75% ibuprofen: 3.12%) - Paracetamol: 6.25% -Salicyles (Acetylsalicylic acid): 0%. Conclusion: The management of pain in patients under vitamin K antagonists has special features, given their many drug interactions with analgesics and their influence on the evolution of the INR which can have dramatic consequences. As such, special attention must be paid to the use of analgesics in this type of patient.

Keywords: vitamin K antagonists, pain killers, interactions, INR

Procedia PDF Downloads 297