Search results for: host transcriptome and drug repurposing
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2914

Search results for: host transcriptome and drug repurposing

1864 Characterization of Herberine Hydrochloride Nanoparticles

Authors: Bao-Fang Wen, Meng-Na Dai, Gao-Pei Zhu, Chen-Xi Zhang, Jing Sun, Xun-Bao Yin, Yu-Han Zhao, Hong-Wei Sun, Wei-Fen Zhang

Abstract:

A drug-loaded nanoparticles containing berberine hydrochloride (BH/FA-CTS-NPs) was prepared. The physicochemical characterizations of BH/FA-CTS-NPs and the inhibitory effect on the HeLa cells were investigated. Folic acid-conjugated chitosan (FA-CTS) was prepared by amino reaction of folic acid active ester and chitosan molecules; BH/FA-CTS-NPs were prepared using ionic cross-linking technique with BH as a model drug. The morphology and particle size were determined by Transmission Electron Microscope (TEM). The average diameters and polydispersity index (PDI) were evaluated by Dynamic Light Scattering (DLS). The interaction between various components and the nanocomplex were characterized by Fourier Transform Infrared Spectroscopy (FT-IR). The entrapment efficiency (EE), drug-loading (DL) and in vitro release were studied by UV spectrophotometer. The effect of cell anti-migratory and anti-invasive actions of BH/FA-CTS-NPs were investigated using MTT assays, wound healing assays, Annexin-V-FITC single staining assays, and flow cytometry, respectively. HeLa nude mice subcutaneously transplanted tumor model was established and treated with different drugs to observe the effect of BH/FA-CTS-NPs in vivo on HeLa bearing tumor. The BH/FA-CTS-NPs prepared in this experiment have a regular shape, uniform particle size, and no aggregation phenomenon. The results of DLS showed that mean particle size, PDI and Zeta potential of BH/FA-CTS NPs were (249.2 ± 3.6) nm, 0.129 ± 0.09, 33.6 ± 2.09, respectively, and the average diameter and PDI were stable in 90 days. The results of FT-IR demonstrated that the characteristic peaks of FA-CTS and BH/FA-CTS-NPs confirmed that FA-CTS cross-linked successfully and BH was encapsulated in NPs. The EE and DL amount were (79.3 ± 3.12) % and (7.24 ± 1.41) %, respectively. The results of in vitro release study indicated that the cumulative release of BH/FA-CTS NPs was (89.48±2.81) % in phosphate-buffered saline (PBS, pH 7.4) within 48h; these results by MTT assays and wund healing assays indicated that BH/FA-CTS NPs not only inhibited the proliferation of HeLa cells in a concentration and time-dependent manner but can induce apoptosis as well. The subcutaneous xenograft tumor formation rate of human cervical cancer cell line HeLa in nude mice was 98% after inoculation for 2 weeks. Compared with BH group and BH/CTS-NPs group, the xenograft tumor growth of BH/FA-CTS-NPs group was obviously slower; the result indicated that BH/FA-CTS-NPs could significantly inhibit the growth of HeLa xenograft tumor. BH/FA-CTS NPs with the sustained release effect could be prepared successfully by the ionic crosslinking method. Considering these properties, block proliferation and impairing the migration of the HeLa cell line, BH/FA-CTS NPs could be an important compound for consideration in the treatment of cervical cancer.

Keywords: folic-acid, chitosan, berberine hydrochloride, nanoparticles, cervical cancer

Procedia PDF Downloads 105
1863 Status and Results from EXO-200

Authors: Ryan Maclellan

Abstract:

EXO-200 has provided one of the most sensitive searches for neutrinoless double-beta decay utilizing 175 kg of enriched liquid xenon in an ultra-low background time projection chamber. This detector has demonstrated excellent energy resolution and background rejection capabilities. Using the first two years of data, EXO-200 has set a limit of 1.1x10^25 years at 90% C.L. on the neutrinoless double-beta decay half-life of Xe-136. The experiment has experienced a brief hiatus in data taking during a temporary shutdown of its host facility: the Waste Isolation Pilot Plant. EXO-200 expects to resume data taking in earnest this fall with upgraded detector electronics. Results from the analysis of EXO-200 data and an update on the current status of EXO-200 will be presented.

Keywords: double-beta, Majorana, neutrino, neutrinoless

Procedia PDF Downloads 398
1862 Evaluation of Central Nervous System Activity of Synthesized 5, 5-Diphenylimidazolidine-2, 4-Dione Derivatives

Authors: Shweta Verma

Abstract:

Background: Epilepsy is a chronic non-communicable central nervous system (CNS) disorder which affects a large population of all ages. Different classes of drugs are used for the treatment of this neurological disorder, but due to augmented drug resistance and side effects, these drugs become incompetent. Therefore, we design the synthesis of ten new derivatives of Phenytoin. The moiety of Phenytoin was hybridized with different phenols by using three step approach. The synthesized molecules were then investigated for different physicochemical parameters, such as Log P values using diverse software programs and to predict the potential to cross the blood-brain barrier. Objective: The Phenytoin derivatives were designed, synthesized, and characterized to meet the structural necessities indispensable for antiepileptic activity. Method: Firstly, the chloroacetylation of the 5,5-diphenyl hydantoin was carried out, and then various substituted phenols were added to it. The synthesized compounds were characterized and evaluated for antianxiety activity by elevated plus maze method and antiepileptic activity by using subcutaneous pentylenetetrazole (scPTZ) and maximal electroshock (MES) models and neurotoxicity. Result: The number of derivatives of 5,5-diphenyl hydantoin was developed and optimized. The number of parameters was optimized which reveal that the compound containing chloro group such as C3 and C6 showed imperative potential when compared with the standard drug Diazepam. Other compounds containing nitro and methyl group were also found to possess activity. Conclusion: It was summarized that the new compounds of 5,5-diphenyl hydantoin derivatives were synthesized. The results of the data show that the compound containing chloro group is more potent for CNS activity. The new compounds have the probability of being optimized further to engender new scaffolds to treat various CNS disorders.

Keywords: phenytoin, parameters, CNS activity, blood-brain barrier, Log P, CNS active

Procedia PDF Downloads 53
1861 Tuberculosis (TB) and Lung Cancer

Authors: Asghar Arif

Abstract:

Lung cancer has been recognized as one of the greatest common cancers, causing the annual mortality rate of about 1.2 million people in the world. Lung cancer is the most prevalent cancer in men and the third-most common cancer among women (after breast and digestive cancers).Recent evidences have shown the inflammatory process as one of the potential factors of cancer. Tuberculosis (TB), pneumonia, and chronic bronchitis are among the most important inflammation-inducing factors in the lungs, among which TB has a more profound role in the emergence of cancer.TB is one of the important mortality factors throughout the world, and 205,000 death cases are reported annually due to this disease. Chronic inflammation and fibrosis due to TB can induce genetic mutation and alternations. Parenchyma tissue of lung is involved in both diseases of TB and lung cancer, and continuous cough in lung cancer, morphological vascular variations, lymphocytosis processes, and generation of immune system mediators such as interleukins, are all among the factors leading to the hypothesis regarding the role of TB in lung cancer Some reports have shown that the induction of necrosis and apoptosis or TB reactivation, especially in patients with immune-deficiency, may result in increasing IL-17 and TNF_α, which will either decrease P53 activity or increase the expression of Bcl-2, decrease Bax-T, and cause the inhibition of caspase-3 expression due to decreasing the expression of mitochondria cytochrome oxidase. It has been also indicated that following the injection of BCG vaccine, the host immune system will be reinforced, and in particular, the rates of gamma interferon, nitric oxide, and interleukin-2 are increased. Therefore, CD4 + lymphocyte function will be improved, and the person will be immune against cancer.Numerous prospective studies have so far been conducted on the role of TB in lung cancer, and it seems that this disease is effective in that particular cancer.One of the main challenges of lung cancer is its correct and timely diagnosis. Unfortunately, clinical symptoms (such as continuous cough, hemoptysis, weight loss, fever, chest pain, dyspnea, and loss of appetite) and radiological images are similar in TB and lung cancer. Therefore, anti-TB drugs are routinely prescribed for the patients in the countries with high prevalence of TB, like Pakistan. Regarding the similarity in clinical symptoms and radiological findings of lung cancer, proper diagnosis is necessary for TB and respiratory infections due to nontuberculousmycobacteria (NTM). Some of the drug resistive TB cases are, in fact, lung cancer or NTM lung infections. Acid-fast staining and histological study of phlegm and bronchial washing, culturing and polymerase chain reaction TB are among the most important solutions for differential diagnosis of these diseases. Briefly, it is assumed that TB is one of the risk factors for cancer. Numerous studies have been conducted in this regard throughout the world, and it has been observed that there is a significant relationship between previous TB infection and lung cancer. However, to prove this hypothesis, further and more extensive studies are required. In addition, as the clinical symptoms and radiological findings of TB, lung cancer, and non-TB mycobacteria lung infections are similar, they can be misdiagnosed as TB.

Keywords: TB and lung cancer, TB people, TB servivers, TB and HIV aids

Procedia PDF Downloads 61
1860 Time-dependent Association between Recreational Cannabinoid Use and Memory Performance in Healthy Adults: A Neuroimaging Study of Human Connectome Project

Authors: Kamyar Moradi

Abstract:

Background: There is mixed evidence regarding the association between recreational cannabinoid use and memory performance. One of the major reasons for the present controversy is different cannabinoid use-related covariates that influence the cognitive status of an individual. Adjustment of these confounding variables provides accurate insight into the real effects of cannabinoid use on memory status. In this study, we sought to investigate the association between recent recreational cannabinoid use and memory performance while correcting the model for other possible covariates such as demographic characteristics and duration, and amount of cannabinoid use. Methods: Cannabinoid users were assigned to two groups based on the results of THC urine drug screen test (THC+ group: n = 110, THC- group: n = 410). THC urine drug screen test has a high sensitivity and specificity in detecting cannabinoid use in the last 3-4 weeks. The memory domain of NIH Toolbox battery and brain MRI volumetric measures were compared between the groups while adjusting for confounding variables. Results: After Benjamini-Hochberg p-value correction, the performance in all of the measured memory outcomes, including vocabulary comprehension, episodic memory, executive function/cognitive flexibility, processing speed, reading skill, working memory, and fluid cognition, were significantly weaker in THC+ group (p values less than 0.05). Also, volume of gray matter, left supramarginal, right precuneus, right inferior/middle temporal, right hippocampus, left entorhinal, and right pars orbitalis regions were significantly smaller in THC+ group. Conclusions: this study provides evidence regarding the acute effect of recreational cannabis use on memory performance. Further studies are warranted to confirm the results.

Keywords: brain MRI, cannabis, memory, recreational use, THC urine test

Procedia PDF Downloads 175
1859 Lipid-Chitosan Hybrid Nanoparticles for Controlled Delivery of Cisplatin

Authors: Muhammad Muzamil Khan, Asadullah Madni, Nina Filipczek, Jiayi Pan, Nayab Tahir, Hassan Shah, Vladimir Torchilin

Abstract:

Lipid-polymer hybrid nanoparticles (LPHNP) are delivery systems for controlled drug delivery at tumor sites. The superior biocompatible properties of lipid and structural advantages of polymer can be obtained via this system for controlled drug delivery. In the present study, cisplatin-loaded lipid-chitosan hybrid nanoparticles were formulated by the single step ionic gelation method based on ionic interaction of positively charged chitosan and negatively charged lipid. Formulations with various chitosan to lipid ratio were investigated to obtain the optimal particle size, encapsulation efficiency, and controlled release pattern. Transmission electron microscope and dynamic light scattering analysis demonstrated a size range of 181-245 nm and a zeta potential range of 20-30 mV. Compatibility among the components and the stability of formulation were demonstrated with FTIR analysis and thermal studies, respectively. The therapeutic efficacy and cellular interaction of cisplatin-loaded LPHNP were investigated using in vitro cell-based assays in A2780/ADR ovarian carcinoma cell line. Additionally, the cisplatin loaded LPHNP exhibited a low toxicity profile in rats. The in-vivo pharmacokinetics study also proved a controlled delivery of cisplatin with enhanced mean residual time and half-life. Our studies suggested that the cisplatin-loaded LPHNP being a promising platform for controlled delivery of cisplatin in cancer therapy.

Keywords: cisplatin, lipid-polymer hybrid nanoparticle, chitosan, in vitro cell line study

Procedia PDF Downloads 116
1858 Development of 4-Allylpyrocatechol Loaded Self-Nanoemulsifying Drug Delivery System for Enhancing Water Solubility and Antibacterial Activity against Oral Pathogenic Bacteria

Authors: Pimpak Phumat, Sakornrat Khongkhunthian, Thomas Rades, Anette Müllertz, Siriporn Okonogi

Abstract:

Self-nanoemulsifying drug delivery systems (SNEDDS) containing 4-allylpyrocatechol (AP) extracted from Piper betle were developed to enhance water solubility of AP by using modeling and design (MODDE) program. The amount of AP in each SNEDDS formulation was determined by using high-performance liquid chromatography. The formulation consisted of 20% Miglyol®812N, 40 % Kolliphor®RH40, 30 % Maisine®35-1 and 10 % ethanol was found to be the best SNEDDS that provided the highest loading capacity of AP. (141.48±15.64 mg/g SNEDDS). The system also showed miscibility with water. The particle shape and size of the AP-SNEDDS after dispersing in water was investigated by using a transmission electron microscope and photon correlation spectrophotometer, respectively. The results showed that they were a spherical shape, having a particle size of 34.27 ± 1.14 nm with a narrow size distribution of 0.17 ± 0.04. The particles showed negative zeta potential with a value of -21.66 ± 2.09 mV. Antibacterial activity of AP-SNEDDS containing 1.5 mg/mL of AP was investigated against Streptococcus intermedius. The effect of this system on S. intermedius cells was observed by a scanning electron microscope (SEM). The results from SEM revealed that the bacterial cells were obviously destroyed. Killing kinetic study of AP-SNEDDS was carried out. It was found that the killing rate of AP-SNEDDS against S. intermedius was dose-dependent and the bacterial reduction was 79.86 ± 0.45 % within 30 min. In comparison with chlorhexidine (CHX), AP-SNEDDS showed similar antibacterial effects against S. intermedius. It is concluded that SNEDDS is a potential system for enhancing water solubility of AP. The antibacterial study reveals that AP-SNEDDS can be a promising system to treat bacterial infection caused by S. intermedius.

Keywords: SNEDDS, 4-allylpyrocathecol, solubility, antibacterial activity, Streptococcus intermedius

Procedia PDF Downloads 100
1857 Intellectual Property Protection of CRISPR Related Technologies

Authors: Zheng Miao, Dennis Fernandez

Abstract:

CRISPR research has the potential to completely transform life science, agriculture, live-stock and the health care industry. The Intellectual Property derived from its research has raised significant attention in the academic as well as the biopharmaceutical industry culminating an urgent need for strategic IP protection. We review the rudimentary concepts and key competitors of CRISPR technologies as well as the paramount strategies for intellectual property protection. Further, we elaborate on prosecution issues related to CRISPR patents as well as possible solutions to various patent laws, interferences and litigation. Finally, we address how the bioinformatics of the CRISPR technology begs an inquiry into issues of privacy and a host of ethical concerns.

Keywords: bioinformatics, CRISPR, biotechnology, intellectual property

Procedia PDF Downloads 235
1856 Epiphytic Growth on Filamentous Bacteria Found in Activated Sludge: A Morphological Approach

Authors: Thobela Conco, Sheena Kumari, Thor Stenstrom, Simona Rosetti, Valter Tandoi, Faizal Bux

Abstract:

Filamentous bacteria are well documented as causative agents of bulking and foaming in the biological wastewater treatment process. These filamentous bacteria are however closely associated with other non-filamentous organism forming a micro-niche. Among these specific epiphytic bacteria attach to filaments in the consortium of organisms that make up the floc. Neither the eco-physiological role of the epiphytes nor the nature of the interaction between the epiphytic bacteria and the filament hosts they colonize is well understood and in need of in-depth investigations. The focus of this presentation is on the interaction between the epiphytic bacteria and the filament host. Samples from the activated sludge treatment have been repeatedly collected from several wastewater treatment plants in KwaZulu Natal. Extensive investigations have been performed with SEM and TEM electron microscopy, Polarized Light Microscopy with Congo red staining, and Thioflavin T staining to document the interaction. SEM was used to document the morphology of both the filament host and their epiphytes counterparts with the focus on the interface/point of contact between the two, while the main focus of the TEM investigations with the higher magnification aimed to document the ultra-structure features of two organisms relating to the interaction. The interaction of the perpendicular attachment partly seems to be governed by the physiological status of the filaments. The attachment further seems to trigger a response in the filaments with distinct internal visible structures at the attachment sites. It is postulated that these structures most likely are amyloid fibrils. Amyloid fibrils may play an overarching role in different types of attachments and has earlier been noted to play a significant role in biofilm formation in activated sludge. They also play a medical role in degenerative diseases such as Alzheimer’s and Diabetes. Further studies aims to define the eco-physiological role of amyloid fibrils in filamentous bacteria, based on their observed presence at interaction sites in this study. This will also relate to additional findings where selectivity within the species of epiphytes attaching to the selected filaments has been noted. The practical implications of the research findings is still to be determined, but the ecophysiological interaction between two closely associated species or groups may have significant impact in the future understanding of wastewater treatment processes and broaden existing knowledge on population dynamics.

Keywords: activated sludge, amyloid proteins, epiphytic bacteria, filamentous bacteria

Procedia PDF Downloads 414
1855 Application of Computational Chemistry for Searching Anticancer Derivatives of 2-Phenazinamines as Bcr-Abl Tyrosine Kinase Inhibitors

Authors: Gajanan M. Sonwane

Abstract:

The computational studies on 2-phenazinamines with their protein targets have been carried out to design compounds with potential anticancer activity. This strategy of designing compounds possessing selectivity over specific tyrosine kinase has been achieved through G-QSAR and molecular docking studies. The objective of this research has been to design newer 2-phenazinamine derivatives as Bcr-Abl tyrosine kinase inhibitors by G-QSAR, molecular docking studies followed by wet-lab studies along with evaluation of their anticancer potential. Computational chemistry was done by using VLife MDS 4.3 and Autodock 4.2 followed by wet-lab experiments for synthesizing 2-phenazinamine derivatives. The chemical structures of ligands in 2D were drawn by employing Chemdraw 2D Ultra 8.0 and were converted into 3D. These were optimized by using a semi-empirical method called MOPAC. The protein structure was retrieved from RCSC protein data bank as a PDB file. The binding interactions of protein and ligands were done by using PYMOL. The molecular properties of the designed compounds were predicted in silico by using Osiris property explorer. The parent compound 2-phenazinamine was synthesized by reduction of 2, 4-dinitro-N-phenyl-benzenamine in the presence of tin chloride followed by cyclization in the presence of nitrobenzene and magnesium sulfate. The derivatization at the amino function of 2-phenazinamine was performed by treating parent compound with various aldehydes in the presence of dicyclohexylcarbodiimide (DCC) and urea to afford 2-(2-chlorophenyl)-3-(phenazine-2-yl) thiazolidine-4-one. Synthesized 39 novel derivatives of 2-phenazinamine and performed antioxidant activity, anti antiproliferative on the bulb of onion and anticancer activity on cell line showing significant competition with marked blockbuster drug imatinib.

Keywords: computer-aided drug design, tyrosin kinases, anticancer, docking

Procedia PDF Downloads 122
1854 Pulsed-Wave Doppler Ultrasonographic Assessment of the Maximum Blood Velocity in Common Carotid Artery in Horses after Administration of Ketamine and Acepromazine

Authors: Saman Ahani, Aboozar Dehghan, Roham Vali, Hamid Salehian, Amin Ebrahimi

Abstract:

Pulsed-wave (PW) doppler ultrasonography is a non-invasive, relatively accurate imaging technique that can measure blood speed. The imaging could be obtained via the common carotid artery, as one of the main vessels supplying the blood of vital organs. In horses, factors such as susceptibility to depression of the cardiovascular system and their large muscular mass have rendered them vulnerable to changes in blood speed. One of the most important factors causing blood velocity changes is the administration of anesthetic drugs, including Ketamine and Acepromazine. Thus, in this study, the Pulsed-wave doppler technique was performed to assess the highest blood velocity in the common carotid artery following administration of Ketamine and Acepromazine. Six male and six female healthy Kurdish horses weighing 351 ± 46 kg (mean ± SD) and aged 9.2 ± 1.7 years (mean ± SD) were housed under animal welfare guidelines. After fasting for six hours, the normal blood flow velocity in the common carotid artery was measured using a Pulsed-wave doppler ultrasonography machine (BK Medical, Denmark), and a high-frequency linear transducer (12 MHz) without applying any sedative drugs as a control group. The same procedure was repeated after each individual received the following medications: 1.1, 2.2 mg/kg Ketamine (Pfizer, USA), and 0.5, 1 mg/kg Acepromizine (RACEHORSE MEDS, Ukraine), with an interval of 21 days between the administration of each dose and/or drug. The ultrasonographic study was done five (T5) and fifteen (T15) minutes after injecting each dose intravenously. Lastly, the statistical analysis was performed using SPSS software version 22 for Windows and a P value less than 0.05 was considered to be statistically significant. Five minutes after administration of Ketamine (1.1, 2.2 mg/kg) in both male and female horses, the blood velocity decreased to 38.44, 34.53 cm/s in males, and 39.06, 34.10 cm/s in females in comparison to the control group (39.59 and 40.39 cm/s in males and females respectively) while administration of 0.5 mg/kg Acepromazine led to a significant rise (73.15 and 55.80 cm/s in males and females respectively) (p<0.05). It means that the most drastic change in blood velocity, regardless of gender, refers to the latter dose/drug. In both medications and both genders, the increase in doses led to a decrease in blood velocity compared to the lower dose of the same drug. In all experiments in this study, the blood velocity approached its normal value at T15. In another study comparing the blood velocity changes affected by Ketamine and Acepromazine through femoral arteries, the most drastic changes were attributed to Ketamine; however, in this experiment, the maximum blood velocity was observed following administration of Acepromazine via the common carotid artery. Therefore, further experiments using the same medications are suggested using Pulsed-wave doppler measuring the blood velocity changes in both femoral and common carotid arteries simultaneously.

Keywords: Acepromazine, common carotid artery, horse, ketamine, pulsed-wave doppler ultrasonography

Procedia PDF Downloads 110
1853 Mathematical Modelling of Blood Flow with Magnetic Nanoparticles as Carrier for Targeted Drug Delivery in a Stenosed Artery

Authors: Sreeparna Majee, G. C. Shit

Abstract:

A study on targeted drug delivery is carried out in an unsteady flow of blood infused with magnetic NPs (nanoparticles) with an aim to understand the flow pattern and nanoparticle aggregation in a diseased arterial segment having stenosis. The magnetic NPs are supervised by the magnetic field which is significant for therapeutic treatment of arterial diseases, tumor and cancer cells and removing blood clots. Coupled thermal energy have also been analyzed by considering dissipation of energy because of the application of the magnetic field and the viscosity of blood. Simulation technique used to solve the mathematical model is vorticity-stream function formulations in the diseased artery. An elevation in SLP (Specific loss power) is noted in the aortic bloodstream when the agglomeration of nanoparticles is higher. This phenomenon has potential application in the treatment of hyperthermia. The study focuses on the lowering of WSS (Wall Shear Stress) with increasing particle concentration at the downstream of the stenosis which depicts the vigorous flow circulation zone. These low shear stress regions prolong the residing time of the nanoparticles carrying drugs which soaks up the LDL (Low Density Lipoprotein) deposition. Moreover, an increase in NP concentration enhances the Nusselt number which marks the increase of heat transfer from the arterial wall to the surrounding tissues to destroy tumor and cancer cells without affecting the healthy cells. The results have a significant influence in the study of medicine, to treat arterial diseases such as atherosclerosis without the need for surgery which can minimize the expenditures on cardiovascular treatments.

Keywords: magnetic nanoparticles, blood flow, atherosclerosis, hyperthermia

Procedia PDF Downloads 120
1852 Safeners, Tools for Artificial Manipulation of Herbicide Selectivity: A Zea mays Case Study

Authors: Sara Franco Ortega, Alina Goldberg Cavalleri, Nawaporn Onkokesung, Richard Dale, Melissa Brazier-Hicks, Robert Edwards

Abstract:

Safeners are agrochemicals that enhance the selective chemical control of wild grasses by increasing the ability of the crop to metabolise the herbicide. Although these compounds are widely used, their mode of action is not well understood. It is known that safeners enhance the metabolism of herbicides, by up-regulating the associated detoxification system we have termed the xenome. The xenome proteins involved in herbicide metabolism have been previously divided into four different phases, with cytochrome P450s (CYPs) playing a key role in phase I metabolism by catalysing hydroxylation and dealkylation reactions. Subsequently, glutathione S-transferases (GSTs) and UDP-glucosyltransferases lead to the formation of Phase II conjugates prior to their transport into the vacuole by ABCs transporters (Phase III). Maize (Zea mays), was been treated with different safeners to explore the selective induction of xenome proteins, with a special interest in the regulation of the CYP superfamily. Transcriptome analysis enabled the identification of key safener-inducible CYPs that were then functionally assessed to determine their role in herbicide detoxification. In order to do that, CYP’s were codon optimised, synthesised and inserted into the yeast expression vector pYES3 using in-fusion cloning. CYP’s expressed as recombinant proteins in a strain of yeast engineered to contain the P450 co-enzyme (cytochrome P450 reductase) from Arabidopsis. Microsomes were extracted and treated with herbicides of different chemical classes in the presence of the cofactor NADPH. The reaction products were then analysed by LCMS to identify any herbicide metabolites. The results of these studies will be presented with the key CYPs identified in maize used as the starting point to find orthologs in other crops and weeds to better understand their roles in herbicide selectivity and safening.

Keywords: CYPs, herbicide detoxification, LCMS, RNA-Seq, safeners

Procedia PDF Downloads 119
1851 Socio-Economic and Psychological Factors of Moscow Population Deviant Behavior: Sociological and Statistical Research

Authors: V. Bezverbny

Abstract:

The actuality of the project deals with stable growing of deviant behavior’ statistics among Moscow citizens. During the recent years the socioeconomic health, wealth and life expectation of Moscow residents is regularly growing up, but the limits of crime and drug addiction have grown up seriously. Another serious Moscow problem has been economical stratification of population. The cost of identical residential areas differs at 2.5 times. The project is aimed at complex research and the development of methodology for main factors and reasons evaluation of deviant behavior growing in Moscow. The main project objective is finding out the links between the urban environment quality and dynamics of citizens’ deviant behavior in regional and municipal aspect using the statistical research methods and GIS modeling. The conducted research allowed: 1) to evaluate the dynamics of deviant behavior in Moscow different administrative districts; 2) to describe the reasons of crime increasing, drugs addiction, alcoholism, suicides tendencies among the city population; 3) to develop the city districts classification based on the level of the crime rate; 4) to create the statistical database containing the main indicators of Moscow population deviant behavior in 2010-2015 including information regarding crime level, alcoholism, drug addiction, suicides; 5) to present statistical indicators that characterize the dynamics of Moscow population deviant behavior in condition of expanding the city territory; 6) to analyze the main sociological theories and factors of deviant behavior for concretization the deviation types; 7) to consider the main theoretical statements of the city sociology devoted to the reasons for deviant behavior in megalopolis conditions. To explore the level of deviant behavior’ factors differentiation, the questionnaire was worked out, and sociological survey involved more than 1000 people from different districts of the city was conducted. Sociological survey allowed to study the socio-economical and psychological factors of deviant behavior. It also included the Moscow residents’ open-ended answers regarding the most actual problems in their districts and reasons of wish to leave their place. The results of sociological survey lead to the conclusion that the main factors of deviant behavior in Moscow are high level of social inequality, large number of illegal migrants and bums, nearness of large transport hubs and stations on the territory, ineffective work of police, alcohol availability and drug accessibility, low level of psychological comfort for Moscow citizens, large number of building projects.

Keywords: deviant behavior, megapolis, Moscow, urban environment, social stratification

Procedia PDF Downloads 178
1850 An Advanced Approach to Detect and Enumerate Soil-Transmitted Helminth Ova from Wastewater

Authors: Vivek B. Ravindran, Aravind Surapaneni, Rebecca Traub, Sarvesh K. Soni, Andrew S. Ball

Abstract:

Parasitic diseases have a devastating, long-term impact on human health and welfare. More than two billion people are infected with soil-transmitted helminths (STHs), including the roundworms (Ascaris), hookworms (Necator and Ancylostoma) and whipworm (Trichuris) with majority occurring in the tropical and subtropical regions of the world. Despite its low prevalence in developed countries, the removal of STHs from wastewater remains crucial to allow the safe use of sludge or recycled water in agriculture. Conventional methods such as incubation and optical microscopy are cumbersome; consequently, the results drastically vary from person-to-person observing the ova (eggs) under microscope. Although PCR-based methods are an alternative to conventional techniques, it lacks the ability to distinguish between viable and non-viable helminth ova. As a result, wastewater treatment industries are in major need for radically new and innovative tools to detect and quantify STHs eggs with precision, accuracy and being cost-effective. In our study, we focus on the following novel and innovative techniques: -Recombinase polymerase amplification and Surface enhanced Raman spectroscopy (RPA-SERS) based detection of helminth ova. -Use of metal nanoparticles and their relative nanozyme activity. -Colorimetric detection, differentiation and enumeration of genera of helminth ova using hydrolytic enzymes (chitinase and lipase). -Propidium monoazide (PMA)-qPCR to detect viable helminth ova. -Modified assay to recover and enumerate helminth eggs from fresh raw sewage. -Transcriptome analysis of ascaris ova in fresh raw sewage. The aforementioned techniques have the potential to replace current conventional and molecular methods thereby producing a standard protocol for the determination and enumeration of helminth ova in sewage sludge.

Keywords: colorimetry, helminth, PMA-QPCR, nanoparticles, RPA, viable

Procedia PDF Downloads 283
1849 Explaining the Role of Iran Health System in Polypharmacy among the Elderly

Authors: Mohsen Shati, Seyede Salehe Mortazavi, Seyed Kazem Malakouti, Hamidreza Khanke Fazlollah Ahmadi

Abstract:

Taking unnecessary or excessive medication or using drugs with no indication (polypharmacy) by people of all ages, especially the elderly, is associated with increased adverse drug reactions (ADR), medical errors, hospitalization and escalating the costs. It may be facilitated or impeded by the healthcare system. In this study, we are going to describe the role of the health system in the practice of polypharmacy in Iranian elderly. In this Inductive qualitative content analysis using Graneheim and Lundman methods, purposeful sample selection until saturation has been made. Participants have been selected from doctors, pharmacists, policy-makers and the elderly. A total of 25 persons (9 men and 16 women) have participated in this study. Data analysis after incorporating codes with similar characteristics revealed 14 subcategories and six main categories of the referral system, physicians’ accessibility, health data management, drug market, laws enforcement, and social protection. Some of the conditions of the healthcare system have given rise to polypharmacy in the elderly. In the absence of a comprehensive specialty and subspecialty referral system, patients may go to any physician office so may well be confused about numerous doctors' prescriptions. Electronic records not being prepared for the patients, failure to comply with laws, lack of robust enforcement for the existing laws and close surveillance are among the contributing factors. Inadequate insurance and supportive services are also evident. Age-specific care providing has not yet been institutionalized, while, inadequate specialist workforce playing a major role. So, one may not ignore the health system as contributing factor in designing effective interventions to fix the problem.

Keywords: elderly, polypharmacy, health system, qualitative study

Procedia PDF Downloads 137
1848 Biological Studies of N-O Donor 4-Acypyrazolone Heterocycle and Its Pd/Pt Complexes of Therapeutic Importance

Authors: Omoruyi Gold Idemudia, Alexander P. Sadimenko

Abstract:

The synthesis of N-heterocycles with novel properties, having broad spectrum biological activities that may become alternative medicinal drugs, have been attracting a lot of research attention due to the emergence of medicinal drug’s limitations such as disease resistance and their toxicity effects among others. Acylpyrazolones have been employed as pharmaceuticals as well as analytical reagent and their application as coordination complexes with transition metal ions have been well established. By way of a condensation reaction with amines acylpyrazolone ketones form a more chelating and superior group of compounds known as azomethines. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one was reacted with phenylhydrazine to get a new phenylhydrazone which was further reacted with aqueous solutions of palladium and platinum salts, in an effort towards the discovery of transition metal based synthetic drugs. The compounds were characterized by means of analytical, spectroscopic, thermogravimetric analysis TGA, as well as x-ray crystallography. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one phenylhydrazone crystallizes in a triclinic crystal system with a P-1 (No. 2) space group based on x-ray crystallography. The bidentate ON ligand formed a square planar geometry on coordinating with metal ions based on FTIR, electronic and NMR spectra as well as magnetic moments. Reported compounds showed antibacterial activities against the nominated bacterial isolates using the disc diffusion technique at 20 mg/ml in triplicates. The metal complexes exhibited a better antibacterial activity with platinum complex having an MIC value of 0.63 mg/ml. Similarly, ligand and complexes also showed antioxidant scavenging properties against 2, 2-diphenyl-1-picrylhydrazyl DPPH radical at 0.5mg/ml relative to ascorbic acid (standard drug).

Keywords: acylpyrazolone, antibacterial studies, metal complexes, phenylhydrazone, spectroscopy

Procedia PDF Downloads 237
1847 Reliability of Clinical Coding in Accurately Estimating the Actual Prevalence of Adverse Drug Event Admissions

Authors: Nisa Mohan

Abstract:

Adverse drug event (ADE) related hospital admissions are common among older people. The first step in prevention is accurately estimating the prevalence of ADE admissions. Clinical coding is an efficient method to estimate the prevalence of ADE admissions. The objective of the study is to estimate the rate of under-coding of ADE admissions in older people in New Zealand and to explore how clinical coders decide whether or not to code an admission as an ADE. There has not been any research in New Zealand to explore these areas. This study is done using a mixed-methods approach. Two common and serious ADEs in older people, namely bleeding and hypoglycaemia were selected for the study. In study 1, eight hundred medical records of people aged 65 years and above who are admitted to hospital due to bleeding and hypoglycemia during the years 2015 – 2016 were selected for quantitative retrospective medical records review. This selection was made to estimate the proportion of ADE-related bleeding and hypoglycemia admissions that are not coded as ADEs. These files were reviewed and recorded as to whether the admission was caused by an ADE. The hospital discharge data were reviewed to check whether all the ADE admissions identified in the records review were coded as ADEs, and the proportion of under-coding of ADE admissions was estimated. In study 2, thirteen clinical coders were selected to conduct qualitative semi-structured interviews using a general inductive approach. Participants were selected purposively based on their experience in clinical coding. Interview questions were designed in a way to investigate the reasons for the under-coding of ADE admissions. The records review study showed that 35% (Cl 28% - 44%) of the ADE-related bleeding admissions and 22% of the ADE-related hypoglycemia admissions were not coded as ADEs. Although the quality of clinical coding is high across New Zealand, a substantial proportion of ADE admissions were under-coded. This shows that clinical coding might under-estimate the actual prevalence of ADE related hospital admissions in New Zealand. The interviews with the clinical coders added that lack of time for searching for information to confirm an ADE admission, inadequate communication with clinicians, along with coders’ belief that an ADE is a small thing might be the potential reasons for the under-coding of the ADE admissions. This study urges the coding policymakers, auditors, and trainers to engage with the unconscious cognitive biases and short-cuts of the clinical coders. These results highlight that further work is needed on interventions to improve the clinical coding of ADE admissions, such as providing education to coders about the importance of ADEs, education to clinicians about the importance of clear and confirmed medical records entries, availing pharmacist service to improve the detection and clear documentation of ADE admissions and including a mandatory field in the discharge summary about external causes of diseases.

Keywords: adverse drug events, bleeding, clinical coders, clinical coding, hypoglycemia

Procedia PDF Downloads 112
1846 Mandatory Wellness Assessments for Medical Students at the University of Ottawa

Authors: Haykal. Kay-Anne

Abstract:

The health and well-being of students is a priority for the Faculty of Medicine at the University of Ottawa. The demands of medical studies are extreme, and many studies confirm that the prevalence of psychological distress is very high among medical students and that it is higher than that of the general population of the same age. The main goal is to identify risk factors for mental health among medical students at the University of Ottawa. The secondary objectives are to determine the variation of these risk factors according to demographic variables, as well as to determine if there is a change in the mental health of students during the 1st and 3rd years of their study. Medical students have a mandatory first and third-year wellness check meeting. This assessment includes a questionnaire on demographic information, mental health, and risk factors such as physical health, sleep, social support, financial stress, education and career, stress and drug use and/or alcohol. Student responses were converted to numerical values and analyzed statistically. The results show that 61% of the variation in the mean of the mental health score is explained by the following risk factors (R2 = 0.61, F (9.396) = 67.197, p < 0.01): lack of sleep and fatigue (β = 0.281, p < 0.001), lack of social support (β = 0.217, p <0.001), poor study or career development (β = 0.195, p < 0.001) and an increase stress and drug and alcohol use (β = -0.239, p < 0.001). No demographic variable has a significant effect on the presence of risk factors. In addition, fixed-effects regression demonstrated significantly lower mental health (p < 0.1) among first-year students (M = 0.587, SD = 0.072) than among third-year students (M = 0.719, SD = 0.071). This preliminary study indicates the need to continue data collection and analysis to increase the significance of the study results. As risk factors are present at the beginning of medical studies, it is important to offer resources to students very early in their medical studies and to have close monitoring and supervision.

Keywords: assessment of mental health, medical students, risk factors for mental health, wellness assessment

Procedia PDF Downloads 106
1845 High Throughput Virtual Screening against ns3 Helicase of Japanese Encephalitis Virus (JEV)

Authors: Soma Banerjee, Aamen Talukdar, Argha Mandal, Dipankar Chaudhuri

Abstract:

Japanese Encephalitis is a major infectious disease with nearly half the world’s population living in areas where it is prevalent. Currently, treatment for it involves only supportive care and symptom management through vaccination. Due to the lack of antiviral drugs against Japanese Encephalitis Virus (JEV), the quest for such agents remains a priority. For these reasons, simulation studies of drug targets against JEV are important. Towards this purpose, docking experiments of the kinase inhibitors were done against the chosen target NS3 helicase as it is a nucleoside binding protein. Previous efforts regarding computational drug design against JEV revealed some lead molecules by virtual screening using public domain software. To be more specific and accurate regarding finding leads, in this study a proprietary software Schrödinger-GLIDE has been used. Druggability of the pockets in the NS3 helicase crystal structure was first calculated by SITEMAP. Then the sites were screened according to compatibility with ATP. The site which is most compatible with ATP was selected as target. Virtual screening was performed by acquiring ligands from databases: KinaseSARfari, KinaseKnowledgebase and Published inhibitor Set using GLIDE. The 25 ligands with best docking scores from each database were re-docked in XP mode. Protein structure alignment of NS3 was performed using VAST against MMDB, and similar human proteins were docked to all the best scoring ligands. The low scoring ligands were chosen for further studies and the high scoring ligands were screened. Seventy-three ligands were listed as the best scoring ones after performing HTVS. Protein structure alignment of NS3 revealed 3 human proteins with RMSD values lesser than 2Å. Docking results with these three proteins revealed the inhibitors that can interfere and inhibit human proteins. Those inhibitors were screened. Among the ones left, those with docking scores worse than a threshold value were also removed to get the final hits. Analysis of the docked complexes through 2D interaction diagrams revealed the amino acid residues that are essential for ligand binding within the active site. Interaction analysis will help to find a strongly interacting scaffold among the hits. This experiment yielded 21 hits with the best docking scores which could be investigated further for their drug like properties. Aside from getting suitable leads, specific NS3 helicase-inhibitor interactions were identified. Selection of Target modification strategies complementing docking methodologies which can result in choosing better lead compounds are in progress. Those enhanced leads can lead to better in vitro testing.

Keywords: antivirals, docking, glide, high-throughput virtual screening, Japanese encephalitis, ns3 helicase

Procedia PDF Downloads 211
1844 Microbial Contamination of Haemolymph of Honeybee (Apis mellifera intermissa) Parasitized by Varroa Destructor

Authors: Messaouda Belaid, Salima Kebbouche-Gana

Abstract:

The negative effect of the Varroa bee colony is very important. They cause morphological and physiological changes, causing a decrease in performance of individuals and long-term death of the colony. Indirectly, they weaken the bees become much more sensitive to the different pathogenic organisms naturally present in the colony. This work aims to research secondary infections of microbial origin occurred in the worker bee nurse due to parasitism by Varroa destructor. The feeding behaviour of Varroa may causes damaging host integument. The results show that the microbial contamination enable to be transmitted into honeybee heamocoel are Bacillus sp, Pseudomonas sp, Enterobacter, Aspergillus.

Keywords: honeybee, Apis mellifera intermissa, microbial contamination, Varroa destructor

Procedia PDF Downloads 381
1843 Chitosan Doped Curcumin Gold Clusters Flexible Nanofiber for Wound Dressing and Anticancer Activities

Authors: Saravanan Govindaraju, Kyusik Yun

Abstract:

The purpose of this study is to develop the chitosan doped curcumin gold cluster nanofiber for wound healing and skin cancer drug delivery applications. Chitosan is a typical marine polysaccharide composed of glucosamine and n-acetyl glucosamine biodegradable and biocompatible polymer. Curcumin is a natural bioactive molecule obtained from Curcuma longo, it mostly occurs in some Asian countries like India and China. It has naturally antioxidant, antimicrobial, wound healing and anticancer property. Due to this advantage, we prepared a combination of natural polymer chitosan with Curcumin and gold nanocluster nanofiber (CH-CUR-AuNCs nanofibers). The prepared nanofiber was characterized by using Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). Antibacterial studies were performed with E.coli and S.aureus. Antioxidant assay, drug release test, and cytotoxicity will be evaluated. Prepared nanofiber emits low intensity of red fluorescent. The FTIR confirm the presence of chitosan and Curcumin in the nanofiber. In vitro study clearly shows the antibacterial activity against the gram negative and gram positive bacteria. Particularly, synthesised nanofibers provide better antibacterial activity against gram negative than gram positive. Cytotoxicity study also provides better killing rate in cancer cell, biocompatible with normal cell. Prepared CH-CUR-AuNCs nanofibers provide the better killing rate to bacterial strains and cancer cells. Finally, prepared nanofiber can be possible to use for wound healing dressing, patch for skin cancer and other biomedical applications.

Keywords: curcumin, chitosan, gold clusters, nanofibers

Procedia PDF Downloads 251
1842 Redirecting Photosynthetic Electron Flux in the Engineered Cyanobacterium synechocystis Sp. Pcc 6803 by the Deletion of Flavodiiron Protein Flv3

Authors: K. Thiel, P. Patrikainen, C. Nagy, D. Fitzpatrick, E.-M. Aro, P. Kallio

Abstract:

Photosynthetic cyanobacteria have been recognized as potential future biotechnological hosts for the direct conversion of CO₂ into chemicals of interest using sunlight as the solar energy source. However, in order to develop commercially viable systems, the flux of electrons from the photosynthetic light reactions towards specified target chemicals must be significantly improved. The objective of the study was to investigate whether the autotrophic production efficiency of specified end-metabolites can be improved in engineered cyanobacterial cells by rescuing excited electrons that are normally lost to molecular oxygen due to the cyanobacterial flavodiiron protein Flv1/3. Natively Flv1/3 dissipates excess electrons in the photosynthetic electron transfer chain by directing them to molecular oxygen in Mehler-like reaction to protect photosystem I. To evaluate the effect of flavodiiron inactivation on autotrophic production efficiency in the cyanobacterial host Synechocystis sp. PCC 6803 (Synechocystis), sucrose was selected as the quantitative reporter and a representative of a potential end-product of interest. The concept is based on the native property of Synechocystis to produce sucrose as an intracellular osmoprotectant when exposed to high external ion concentrations, in combination with the introduction of a heterologous sucrose permease (CscB from Escherichia coli), which transports the sucrose out from the cell. In addition, cell growth, photosynthetic gas fluxes using membrane inlet mass spectrometry and endogenous storage compounds were analysed to illustrate the consequent effects of flv deletion on pathway flux distributions. The results indicate that a significant proportion of the electrons can be lost to molecular oxygen via Flv1/3 even when the cells are grown under high CO₂ and that the inactivation of flavodiiron activity can enhance the photosynthetic electron flux towards optionally available sinks. The flux distribution is dependent on the light conditions and the genetic context of the Δflv mutants, and favors the production of either sucrose or one of the two storage compounds, glycogen or polyhydroxybutyrate. As a conclusion, elimination of the native Flv1/3 reaction and concomitant introduction of an engineered product pathway as an alternative sink for excited electrons could enhance the photosynthetic electron flux towards the target endproduct without compromising the fitness of the host.

Keywords: cyanobacterial engineering, flavodiiron proteins, redirecting electron flux, sucrose

Procedia PDF Downloads 111
1841 Bionaut™: A Microrobotic Drug-Device Platform for the Local Treatment of Brainstem Gliomas

Authors: Alex Kiselyov, Suehyun Cho, Darrell Harrington; Florent Cros, Olin Palmer, John Caputo, Michael Kardosh, Eran Oren, William Loudon, Michael Shpigelmacher

Abstract:

Despite the most aggressive surgical and adjuvant therapeutic strategies, treatment of both pediatric and adult brainstem tumors remains problematic. Novel strategies, including targeted biologics, immunotherapy, and specialized delivery systems such as convection-enhanced delivery (CED), have been proposed. While some of these novel treatments are entering phase I trials, the field is still in need of treatment(s) that exhibits dramatically enhanced potency with optimal therapeutic ratio. Bionaut Labs has developed a modular microrobotic platform for performing localized delivery of diverse therapeutics in vivo. Our biocompatible particles (Bionauts™) are externally propelled and visualized in real-time. Bionauts™ are specifically designed to enhance the effect of radiation therapy via anatomically precise delivery of a radiosensitizing agent, as exemplified by temozolomide (TMZ) and Avastin™ to the brainstem gliomas of diverse origin. The treatment protocol is designed to furnish a better therapeutic outcome due to the localized (vs systemic) delivery of the drug to the neoplastic lesion(s) for use as a synergistic combination of radiation and radiosensitizing agent. In addition, the procedure is minimally invasive and is expected to be appropriate for both adult and pediatric patients. Current progress, including platform optimization, selection of the lead radiosensitizer as well as in vivo safety studies of the Bionauts™ in large animals, specifically the spine and the brain of porcine and ovine models, will be discussed.

Keywords: Bionaut, brainstem, glioma, local delivery, micro-robot, radiosensitizer

Procedia PDF Downloads 179
1840 Towards Designing of a Potential New HIV-1 Protease Inhibitor Using Quantitative Structure-Activity Relationship Study in Combination with Molecular Docking and Molecular Dynamics Simulations

Authors: Mouna Baassi, Mohamed Moussaoui, Hatim Soufi, Sanchaita RajkhowaI, Ashwani Sharma, Subrata Sinha, Said Belaaouad

Abstract:

Human Immunodeficiency Virus type 1 protease (HIV-1 PR) is one of the most challenging targets of antiretroviral therapy used in the treatment of AIDS-infected people. The performance of protease inhibitors (PIs) is limited by the development of protease mutations that can promote resistance to the treatment. The current study was carried out using statistics and bioinformatics tools. A series of thirty-three compounds with known enzymatic inhibitory activities against HIV-1 protease was used in this paper to build a mathematical model relating the structure to the biological activity. These compounds were designed by software; their descriptors were computed using various tools, such as Gaussian, Chem3D, ChemSketch and MarvinSketch. Computational methods generated the best model based on its statistical parameters. The model’s applicability domain (AD) was elaborated. Furthermore, one compound has been proposed as efficient against HIV-1 protease with comparable biological activity to the existing ones; this drug candidate was evaluated using ADMET properties and Lipinski’s rule. Molecular Docking performed on Wild Type and Mutant Type HIV-1 proteases allowed the investigation of the interaction types displayed between the proteases and the ligands, Darunavir (DRV) and the new drug (ND). Molecular dynamics simulation was also used in order to investigate the complexes’ stability, allowing a comparative study of the performance of both ligands (DRV & ND). Our study suggested that the new molecule showed comparable results to that of Darunavir and may be used for further experimental studies. Our study may also be used as a pipeline to search and design new potential inhibitors of HIV-1 proteases.

Keywords: QSAR, ADMET properties, molecular docking, molecular dynamics simulation.

Procedia PDF Downloads 12
1839 Determinants of Internationalization of Social Enterprises: A 20-Year Review

Authors: Xiaoqing Li

Abstract:

Social entrepreneurship drives the global movement as social enterprises create best ways to satisfy social needs through connecting international resources. However, what determines social enterprises to internationalize is underexplored. This study aims to answer this question by conducting a systematic review of studies of past 20 years on social enterprises' internationalization. Findings reveal that factors at the individual (entrepreneur), firm, and environment (home and host country) levels determine the degree of social enterprises' internationalization. Future research is challenged by: a. adopting an integrated approach examining the three levels to explain social enterprises' internationalization; b. the different nature of social enterprises from commercial businesses demands scholars to refine and develop appropriate theoretical models to capture the dynamism of social enterprises' internationalization behavior.

Keywords: determinants, entrepreneurship, internationalization, social enterprises

Procedia PDF Downloads 194
1838 The Ameliorative Effects of the Histamine H3 Receptor Antagonist/Inverse Agonist DL77 on MK801-Induced Memory Deficits in Rats

Authors: B. Sadek, N. Khan, Shreesh K. Ojha, Adel Sadeq, D. Lazewska, K. Kiec-Kononowicz

Abstract:

The involvement of Histamine H3 receptors (H3Rs) in memory and the potential role of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer disease (AD) is well established. Therefore, the memory-enhancing effects of the H3R antagonist DL77 on MK801-induced cognitive deficits were evaluated in passive avoidance paradigm (PAP) and novel object recognition (NOR) tasks in adult male rats, applying donepezil (DOZ) as a reference drug. Animals pretreated with acute systemic administration of DL77 (2.5, 5, and 10 mg/kg, i.p.) were significantly ameliorated in regard to MK801-induced memory deficits in PAP. The ameliorative effect of most effective dose of DL77 (5 mg/kg, i.p.) was abrogated when animals were pretreated with a co-injection with the H3R agonist R-(α)-methylhistamine (RAMH, 10 mg/kg, i.p.). Moreover, and in the NOR paradigm, DL77 (5 mg/kg, i.p.) reversed MK801-induced deficits long-term memory (LTM), and the DL77-provided procognitive effect was comparable to that of reference drug DOZ, and was reversed when animals were co-injected with RAMH (10 mg/kg, i.p.). However, DL77(5 mg/kg, i.p.) failed to alter short-term memory (STM) impairment in NOR test. Furthermore, DL77 (5 mg/kg) failed to induce any alterations of anxiety and locomotor behaviors of animals naive to elevated-plus maze (EPM), indicating that the ameliorative effects observed in PAP or NOR tests were not associated to alterations in emotions or in natural locomotion of tested animals. These results reveal the potential contribution of H3Rs in modulating CNS neurotransmission systems associated with neurodegenerative disorders, e.g., AD.

Keywords: histamine H3 receptor, antagonist, learning and memory, Alzheimer's disease, neurodegeneration, passive avoidance paradigm, novel object recognition, behavioral research

Procedia PDF Downloads 139
1837 A Handheld Light Meter Device for Methamphetamine Detection in Oral Fluid

Authors: Anindita Sen

Abstract:

Oral fluid is a promising diagnostic matrix for drugs of abuse compared to urine and serum. Detection of methamphetamine in oral fluid would pave way for the easy evaluation of impairment in drivers during roadside drug testing as well as ensure safe working environments by facilitating evaluation of impairment in employees at workplaces. A membrane-based point-of-care (POC) friendly pre-treatment technique has been developed which aided elimination of interferences caused by salivary proteins and facilitated the demonstration of methamphetamine detection in saliva using a gold nanoparticle based colorimetric aptasensor platform. It was found that the colorimetric response in saliva was always suppressed owing to the matrix effects. By navigating the challenging interfering issues in saliva, we were successfully able to detect methamphetamine at nanomolar levels in saliva offering immense promise for the translation of these platforms for on-site diagnostic systems. This subsequently motivated the development of a handheld portable light meter device that can reliably transduce the aptasensors colorimetric response into absorbance, facilitating quantitative detection of analyte concentrations on-site. This is crucial due to the prevalent unreliability and sensitivity problems of the conventional drug testing kits. The fabricated light meter device response was validated against a standard UV-Vis spectrometer to confirm reliability. The portable and cost-effective handheld detector device features sensitivity comparable to the well-established UV-Vis benchtop instrument and the easy-to-use device could potentially serve as a prototype for a commercial device in the future.

Keywords: aptasensors, colorimetric gold nanoparticle assay, point-of-care, oral fluid

Procedia PDF Downloads 26
1836 The Management of Care by People with Type 2 Diabetes versus the Professional Care at Primary Health Care in Brazil

Authors: Nunila Ferreira de Oliveira, Silvana Martins Mishima

Abstract:

Diabetes mellitus type 2 (DM2) prevalence, is increasing on the world, in Brazil is considered a public health problem. Treatment focuses on glycemic control depending primarily of lifestyle changes - not drug treatment (NDT), may involve drug therapy (DT) and requires continuous health monitoring. In Brazil this monitoring is performed by the Unified Health System (SUS) through Primary Health Care (PHC), which stimulate people with DM2 empowerment for care management. SUS was approved in 1988 and the PHC operationalization was strengthened with the creation of the Family Health Strategy (FHS) in 1994. Our aim was to analyze the people with DM2 participation in front of the care management health monitoring in the FHS. Qualitative research was carried out through non-participant observation of attendance of 25 people with DM2 in the FHS and interviewed at home. Ethical guidelines were followed. It was found that people with DM2 only follow professionals’ recommendations that make sense according to their own conceptions of health/disease; most of them emphasize the importance of (DT) with little emphasis on the NDT, was found great difficulty in the NDT and lack of knowledge about the disease and care. As regards monitoring the FHS, were observed therapeutic practices based on the bio medical model, although the APS search for another care perspective; NDT is not systematically accompanied by the health team and takes place a few educational activities on the DM2 in the FHS, with low user adoption. The work of the FHS is done by multidisciplinary teams, but we see the need for greater participation of nurses in clinical-care follow-up of this population and may also act in adapting to the NDT. Finally we emphasize the need for professional practices that consider the difficulties to care management by people with DM2, especially because of the NDT. It is noticed that the measures recommended by the FHS professionals are not always developed by people with DM2. We must seek the empowerment of people with DM2 to manage the form of care associated with the FHS team, seeking to reduce the incidence of complications and higher quality of life.

Keywords: diabetes mellitus, primary health care, nursing, management of care

Procedia PDF Downloads 442
1835 Treatment of Porphyromonas gingivalis Induced Gingivitis in Albino Rats with Tetracycline-Loaded Nanochitosan, an Immunohistochemical Analysis

Authors: Rania Hanafi Said, Rasha Mohamed Taha

Abstract:

Background: By using nanoparticles as drug delivery, it may be possible to avoid the drawbacks of systemic antibiotic dosing, including bacterial antibiotic resistance. The goal of this study was to see how well tetracycline loaded on nanochitosan worked to treat gingival inflammation in albino rats caused by Porphyromonas gingivalis. The study analyzed immunohistochemically the localization of the pro-inflammatory cytokine Interleukin-1beta (IL-1β). Material and methods: In this study, fifty mature male albino rats weighing 150 to 180 grams each were used. They were randomly divided into five groups. We checked for weight changes in rats. Ten male albino rats were included in Group I, which served as a negative control group. Ten rats were included in Group II, where they were exposed once to Porphyromonas. Group III contained ten rats, which were treated the same as Group II plus daily injections of diluted tetracycline powder at the infection sites. Ten rats in Group IV received the same procedure as those in Group II before receiving daily injections of nanochitosan at the injection sites. Finally, Group V, which had ten rats. Following the same protocol as Group II, they received localized injections of tetracycline loaded on nanochitosan once daily. Rats' gingivae were extracted and prepared after they were anesthetized. The biopsies were examined histologically and immunohistochemically by light microscopy. Results: Groups I and V had a nearly normal histological appearance of gingival tissue. In Groups II, III, and IV, degeneration was seen because the epithelial cells were bigger, collagen fibers were pulling away from the lamina propria connective tissue, and the basement membranes had come to an end. There was no discernible difference between groups V and I when they were examined immunohistochemically. Conclusion: The use of nano chitosan as a tetracycline carrier is a novel technique to overcome the drug's rising level of resistance.

Keywords: Immunohistochemistry, Nanochitosan, porphyromonas gingivitis, Tetracycline

Procedia PDF Downloads 60