Search results for: cervical cancer screening
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3210

Search results for: cervical cancer screening

540 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 101
539 Quantum Chemical Investigation of Hydrogen Isotopes Adsorption on Metal Ion Functionalized Linde Type A and Faujasite Type Zeolites

Authors: Gayathri Devi V, Aravamudan Kannan, Amit Sircar

Abstract:

In the inner fuel cycle system of a nuclear fusion reactor, the Hydrogen Isotopes Removal System (HIRS) plays a pivoted role. It enables the effective extraction of the hydrogen isotopes from the breeder purge gas which helps to maintain the tritium breeding ratio and sustain the fusion reaction. One of the components of HIRS, Cryogenic Molecular Sieve Bed (CMSB) columns with zeolites adsorbents are considered for the physisorption of hydrogen isotopes at 1 bar and 77 K. Even though zeolites have good thermal stability and reduced activation properties making them ideal for use in nuclear reactor applications, their modest capacity for hydrogen isotopes adsorption is a cause of concern. In order to enhance the adsorbent capacity in an informed manner, it is helpful to understand the adsorption phenomena at the quantum electronic structure level. Physicochemical modifications of the adsorbent material enhances the adsorption capacity through the incorporation of active sites. This may be accomplished through the incorporation of suitable metal ions in the zeolite framework. In this work, molecular hydrogen isotopes adsorption on the active sites of functionalized zeolites are investigated in detail using Density Functional Theory (DFT) study. This involves the utilization of hybrid Generalized Gradient Approximation (GGA) with dispersion correction to account for the exchange and correlation functional of DFT. The electronic energies, adsorption enthalpy, adsorption free energy, Highest Occupied Molecular Orbital (HOMO), Lowest Unoccupied Molecular Orbital (LUMO) energies are computed on the stable 8T zeolite clusters as well as the periodic structure functionalized with different active sites. The characteristics of the dihydrogen bond with the active metal sites and the isotopic effects are also studied in detail. Validation studies with DFT will also be presented for adsorption of hydrogen on metal ion functionalized zeolites. The ab-inito screening analysis gave insights regarding the mechanism of hydrogen interaction with the zeolites under study and also the effect of the metal ion on adsorption. This detailed study provides guidelines for selection of the appropriate metal ions that may be incorporated in the zeolites framework for effective adsorption of hydrogen isotopes in the HIRS.

Keywords: adsorption enthalpy, functionalized zeolites, hydrogen isotopes, nuclear fusion, physisorption

Procedia PDF Downloads 152
538 Biodistribution of Fluorescence-Labelled Epidermal Growth Factor Protein from Slow Release Nanozolid Depots in Mouse

Authors: Stefan Gruden, Charlott Brunmark, Bo Holmqvist, Erwin D. Brenndorfer, Martin Johansson, Jian Liu, Ying Zhao, Niklas Axen, Moustapha Hassan

Abstract:

Aim: The study was designed to evaluate the ability of the calcium sulfate-based NanoZolid® drug delivery technology to locally release the epidermal growth factor (EGF) protein while maintaining its biological activity. Methods: NanoZolid-formulated EGF protein labelled with a near-infrared dye (EGF-NIR) depots or EGF-NIR dissolved in PBS were injected subcutaneously into mice bearing EGF receptor (EGFR) positive human A549 lung cancer tumors inoculated subcutaneously. The release and biodistribution of the EGF-NIR were investigated in vivo longitudinally up to 96 hours post-administration, utilizing whole-body fluorescence imaging. In order to confirm the in vivo findings, histological analysis of tumor cryosections was performed to investigate EGF-NIR fluorescent signal and EGFR expression level by immunofluorescence labelling. Results: The in vivo fluorescence imaging showed a controlled release profile of the EGF-NIR loaded in the NanoZolid depots compared to free EGF-NIR. Histological analysis of the tumors further demonstrated a prevailing distribution of EGF-NIR in regions with high levels of EGFR expression. Conclusion: Calcium sulfate based depots can be used to formulate EGF while maintaining its biological activity, e.g., receptor binding capability. This may have good clinical potential for local delivery of biomolecules to enhance treatment efficacy and minimize systemic adverse effects.

Keywords: bioresorbable, calcium sulfate, controlled release, NanoZolid

Procedia PDF Downloads 133
537 Quartz Crystal Microbalance Based Hydrophobic Nanosensor for Lysozyme Detection

Authors: F. Yılmaz, Y. Saylan, A. Derazshamshir, S. Atay, A. Denizli

Abstract:

Quartz crystal microbalance (QCM), high-resolution mass-sensing technique, measures changes in mass on oscillating quartz crystal surface by measuring changes in oscillation frequency of crystal in real time. Protein adsorption techniques via hydrophobic interaction between protein and solid support, called hydrophobic interaction chromatography (HIC), can be favorable in many cases. Some nanoparticles can be effectively applied for HIC. HIC takes advantage of the hydrophobicity of proteins by promoting its separation on the basis of hydrophobic interactions between immobilized hydrophobic ligands and nonpolar regions on the surface of the proteins. Lysozyme is found in a variety of vertebrate cells and secretions, such as spleen, milk, tears, and egg white. Its common applications are as a cell-disrupting agent for extraction of bacterial intracellular products, as an antibacterial agent in ophthalmologic preparations, as a food additive in milk products and as a drug for treatment of ulcers and infections. Lysozyme has also been used in cancer chemotherapy. The aim of this study is the synthesis of hydrophobic nanoparticles for Lysozyme detection. For this purpose, methacryoyl-L-phenylalanine was chosen as a hydrophobic matrix. The hydrophobic nanoparticles were synthesized by micro-emulsion polymerization method. Then, hydrophobic QCM nanosensor was characterized by Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, atomic force microscopy (AFM) and zeta size analysis. Hydrophobic QCM nanosensor was tested for real-time detection of Lysozyme from aqueous solution. The kinetic and affinity studies were determined by using Lysozyme solutions with different concentrations. The responses related to a mass (Δm) and frequency (Δf) shifts were used to evaluate adsorption properties.

Keywords: nanosensor, HIC, lysozyme, QCM

Procedia PDF Downloads 322
536 Deuterium Effect on the Growth of the Fungus Aspergillus Fumigatus and Candida Albicans

Authors: Farzad Doostishoar, Abdolreza Hasanzadeh, Seyed Amin Ayatolahi Mousavi

Abstract:

Introduction and Goals: Deuterium has different action from its isotopes hydrogen in chemical reactions and biochemical processes. It is not a significant difference in heavier atoms between the behavior of heavier isotope and the lighter One but for very lighter atoms it is significant . According to that most of the weight of all creatures body is water natural rate can be significant. In this article we want to study the effect of reduced deuterium on the fungus cell. If we saw the dependence of deuterium concentration of environment on the cells growth we can test this in invivo models too. Methods: First we measured deuterium concentration of the distillated water this analyze was operated by Arak’s heavy water company. Then the deuterium was diluted to ½ ¼ 1/8 1/16 by adding water free of deuterium for making media. In tree of samples the deuterium concentration was increased by adding D2O up to 10,50,100 times more concentrated. For candida albicans growth we used sabor medium and for aspergillus fomigatis growth we used sabor medium containing chloramphenicol. After culturing the funguses species we put the mediums for each species in the shaker incubator for 10 days in 25 centigrade. In different days and times the plates were studied morphologically and some microscopic characteristics were studied too. This experiments and cultures were repeated 3 times. Results: Statistical analyzes by paired-sample T test showed that aspergilus fomigatoos growth was decreased in concentration of 72 ppm( half deuterium concentration of negative control) significantly. In deuterium concentration reduction the growth reduce into the negative control significantly. The project results showed that candida albicans was sensitive to reduce and decrease of the deuterium in all concentrations.

Keywords: deuterium, cancer cell, growth, candida albicans

Procedia PDF Downloads 376
535 Linking Metabolism, Pluripotency and Epigenetic Changes during Early Differentiation of Embryonic Stem Cells

Authors: Arieh Moussaieff, Bénédicte Elena-Herrmann, Yaakov Nahmias, Daniel Aberdam

Abstract:

Differentiation of pluripotent stem cells is a slow process, marked by the gradual loss of pluripotency factors over days in culture. While the first few days of differentiation show minor changes in the cellular transcriptome, intracellular signaling pathways remain largely unknown. Recently, several groups demonstrated that the metabolism of pluripotent mouse and human cells is different from that of somatic cells, showing a marked increase in glycolysis previously identified in cancer as the Warburg effect. Here, we sought to identify the earliest metabolic changes induced at the first hours of differentiation. High-resolution NMR analysis identified 35 metabolites and a distinct, gradual transition in metabolism during early differentiation. Metabolic and transcriptional analyses showed the induction of glycolysis toward acetate and acetyl-coA in pluripotent cells, and an increase in cholesterol biosynthesis during early differentiation. Importantly, this metabolic pathway regulated differentiation of human and mouse embryonic stem cells. Acetate delayed differentiation preventing differentiation-induced histone de-acetylation in a dose-dependent manner. Glycolytic inhibitors upstream of acetate caused differentiation of pluripotent cells, while those downstream delayed differentiation. Our data suggests that a rapid loss of glycolysis in early differentiation down-regulates acetate and acetyl-coA production, causing a loss of histone acetylation and concomitant loss of pluripotency. It demonstrate that pluripotent stem cells utilize a novel metabolism pathway to maintain pluripotency through acetate/acetyl-coA and highlights the important role metabolism plays in pluripotency and early differentiation of stem cells.

Keywords: pluripotency, metabolomics, epigenetics, acetyl-coA

Procedia PDF Downloads 439
534 Gender Equality at Workplace in Iran - Strategies and Successes Against Systematic Bias

Authors: Leila Sadeghi

Abstract:

Gender equality is a critical concern in the workplace, particularly in Iran, where legal and social barriers contribute to significant disparities. This abstract presents a case study of Dahi Bondad Co., a company based in Tehran, Iran that recognized the urgency of addressing the gender gap within its organization. Through a comprehensive investigation, the company identified issues related to biased recruitment, pay disparities, promotion biases, internal barriers, and everyday boundaries. This abstract highlights the strategies implemented by Dahi Bondad Co. to combat these challenges and foster gender equality. The company revised its recruitment policies, eliminated gender-specific language in job advertisements, and implemented blind resume screening to ensure equal opportunities for all applicants. Comprehensive pay equity analyses were conducted, leading to salary adjustments based on qualifications and experience to rectify pay disparities. Clear and transparent promotion criteria were established, and training programs were provided to decision-makers to raise awareness about unconscious biases. Additionally, mentorship and coaching programs were introduced to support female employees in overcoming self-limiting beliefs and imposter syndrome. At the same time, practical workshops and gamification techniques were employed to boost confidence and encourage women to step out of their comfort zones. The company also recognized the importance of dress codes and allowed optional hijab-wearing, respecting local traditions while promoting individual freedom. As a result of these strategies, Dahi Bondad Co. successfully fostered a more equitable and empowering work environment, leading to increased job satisfaction for both male and female employees within a short timeframe. This case study serves as an example of practical approaches that human resource managers can adopt to address gender inequality in the workplace, providing valuable insights for organizations seeking to promote gender equality in similar contexts.

Keywords: gender equality, human resource strategies, legal barrier, social barrier, successful result, successful strategies, workplace in Iran

Procedia PDF Downloads 42
533 Gut Microbiota in Patients with Opioid Use Disorder: A 12-week Follow up Study

Authors: Sheng-Yu Lee

Abstract:

Aim: Opioid use disorder is often characterized by repetitive drug-seeking and drug-taking behaviors with severe public health consequences. Animal model showed that opioid-induced perturbations in the gut microbiota causally relate to neuroinflammation, deficits in reward responding, and opioid tolerance, possibly due to changes in gut microbiota. Therefore, we propose that the dysbiosis of gut microbiota can be associated with pathogenesis of opioid dependence. In this current study, we explored the differences in gut microbiota between patients and normal controls and in patients before and after initiation of methadone treatment program for 12 weeks. Methods: Patients with opioid use disorder between 20 and 65 years were recruited from the methadone maintenance outpatient clinic in 2 medical centers in the Southern Taiwan. Healthy controls without any family history of major psychiatric disorders (schizophrenia, bipolar disorder and major depressive disorder) were recruited from the community. After initial screening, 15 patients with opioid use disorder joined the study for initial evaluation (Week 0), 12 of them completed the 12-week follow-up while receiving methadone treatment and ceased heroin use (Week 12). Fecal samples were collected from the patients at baseline and the end of 12th week. A one-time fecal sample was collected from the healthy controls. The microbiota of fecal samples were investigated using 16S rRNA V3V4 amplicon sequencing, followed by bioinformatics and statistical analyses. Results: We found no significant differences in species diversity in opioid dependent patients between Week 0 and Week 12, nor compared between patients at both points and controls. For beta diversity, using principal component analysis, we found no significant differences between patients at Week 0 and Week 12, however, both patient groups showed significant differences compared to control (P=0.011). Furthermore, the linear discriminant analysis effect size (LEfSe) analysis was used to identify differentially enriched bacteria between opioid use patients and healthy controls. Compared to controls, the relative abundance of Lactobacillaceae Lactobacillus (L. Lactobacillus), Megasphaera Megasphaerahexanoica (M. Megasphaerahexanoica) and Caecibacter Caecibactermassiliensis (C Caecibactermassiliensis) were increased in patients at Week 0, while Coriobacteriales Atopobiaceae (C. Atopobiaceae), Acidaminococcus Acidaminococcusintestini (A. Acidaminococcusintestini) and Tractidigestivibacter Tractidigestivibacterscatoligenes (T. Tractidigestivibacterscatoligenes) were increased in patients at Week 12. Conclusion: In conclusion, we suggest that the gut microbiome community maybe linked to opioid use disorder, such differences may not be altered even after 12-week of cessation of opioid use.

Keywords: opioid use disorder, gut microbiota, methadone treatment, follow up study

Procedia PDF Downloads 75
532 Improving Patient-Care Services at an Oncology Center with a Flexible Adaptive Scheduling Procedure

Authors: P. Hooshangitabrizi, I. Contreras, N. Bhuiyan

Abstract:

This work presents an online scheduling problem which accommodates multiple requests of patients for chemotherapy treatments in a cancer center of a major metropolitan hospital in Canada. To solve the problem, an adaptive flexible approach is proposed which systematically combines two optimization models. The first model is intended to dynamically schedule arriving requests in the form of waiting lists whereas the second model is used to reschedule the already booked patients with the goal of finding better resource allocations when new information becomes available. Both models are created as mixed integer programming formulations. Various controllable and flexible parameters such as deviating the prescribed target dates by a pre-determined threshold, changing the start time of already booked appointments and the maximum number of appointments to move in the schedule are included in the proposed approach to have sufficient degrees of flexibility in handling arrival requests and unexpected changes. Several computational experiments are conducted to evaluate the performance of the proposed approach using historical data provided by the oncology clinic. Our approach achieves outstandingly better results as compared to those of the scheduling system being used in practice. Moreover, several analyses are conducted to evaluate the effect of considering different levels of flexibility on the obtained results and to assess the performance of the proposed approach in dealing with last-minute changes. We strongly believe that the proposed flexible adaptive approach is very well-suited for implementation at the clinic to provide better patient-care services and to utilize available resource more efficiently.

Keywords: chemotherapy scheduling, multi-appointment modeling, optimization of resources, satisfaction of patients, mixed integer programming

Procedia PDF Downloads 128
531 A Review of Accuracy Optical Surface Imaging Systems for Setup Verification During Breast Radiotherapy Treatment

Authors: Auwal Abubakar, Ahmed Ahidjo, Shazril Imran Shaukat, Noor Khairiah A. Karim, Gokula Kumar Appalanaido, Hafiz Mohd Zin

Abstract:

Background: The use of optical surface imaging systems (OSISs) is increasingly becoming popular in radiotherapy practice, especially during breast cancer treatment. This study reviews the accuracy of the available commercial OSISs for breast radiotherapy. Method: A literature search was conducted and identified the available commercial OSISs from different manufacturers that are integrated into radiotherapy practice for setup verification during breast radiotherapy. Studies that evaluated the accuracy of the OSISs during breast radiotherapy using cone beam computed tomography (CBCT) as a reference were retrieved and analyzed. The physics and working principles of the systems from each manufacturer were discussed together with their respective strength and limitations. Results: A total of five (5) different commercially available OSISs from four (4) manufacturers were identified, each with a different working principle. Six (6) studies were found to evaluate the accuracy of the systems during breast radiotherapy in conjunction with CBCT as a goal standard. The studies revealed that the accuracy of the system in terms of mean difference ranges from 0.1 to 2.1 mm. The correlation between CBCT and OSIS ranges between 0.4 and 0.9. The limit of agreements obtained using bland Altman analysis in the studies was also within an acceptable range. Conclusion: The OSISs have an acceptable level of accuracy and could be used safely during breast radiotherapy. The systems are non-invasive, ionizing radiation-free, and provide real-time imaging of the target surface at no extra concomitant imaging dose. However, the system should only be used to complement rather than replace x-ray-based image guidance techniques such as CBCT.

Keywords: optical surface imaging system, Cone beam computed tomography (CBCT), surface guided radiotherapy, Breast radiotherapy

Procedia PDF Downloads 25
530 Manifestations of Tuberculosis in Otorhinolaryngology Practice: A Retrospective Study Conducted in a Coastal City of South India

Authors: Rithika Sriram, Kiran M. Bhojwani

Abstract:

Introduction : Tuberculosis of the head and neck has proved to be a diagnostic challenge for otorhinolarynologists around the world. These lesions are often misdiagnosed as cancer. So in order to contribute to a better understanding of these lesions, we have conducted our study among patients affected by TB in the head and neck region with the objective of assessing the various manifestations, presentations, diagnostic techniques, risk factors such as smoking and alcohol consumption, coexisting illnesses and treatment modalities. Materials and Methods: This was a retrospective study conducted over a three year period (2012-2014) in 2 hospitals affliated to Kasturba Medical College in Mangalore, South India. A semi structured proforma was used to capture information from the medical records pertaining to the various objectives of the study such as clinical features and history of smoking. Data was analysed using SPSS version 16.0 and results obtained were depicted as percentages. Chi square test was used to find association between the variables and p<0.05 was considered statistically significant. Results: 104 patients were found to have TB of the head and neck and among them,the most common manifestation was found to be Tubercular Lymphadenitis (86.53%), followed by laryngeal TB (4.8%), submandibular gland TB (3.8%), deep neck space abscess(3.8%) and adenotonsillar TB. FNAC was found to be the gold standard for the diagnosis of TB disease of the lymph node.26% of the patients had coexisting HIV infection and 16.3% of the patients had associated pulmonary TB. More than 20% of the patients were smokers. Most patients were treated using ATT. Conclusion: Tuberculosis affecting regions of head and neck is no longer uncommon. Sufficient knowledge and appropriate diagnostic means is required while dealing with these lesions and must be included in the differential diagnosis of pathological lesions of head and neck.

Keywords: FNAC, Mangalore, smoking, tuberculosis

Procedia PDF Downloads 252
529 Screening of Antagonistic/Synergistic Effect between Lactic Acid Bacteria (LAB) and Yeast Strains Isolated from Kefir

Authors: Mihriban Korukluoglu, Goksen Arik, Cagla Erdogan, Selen Kocakoglu

Abstract:

Kefir is a traditional fermented refreshing beverage which is known for its valuable and beneficial properties for human health. Mainly yeast species, lactic acid bacteria (LAB) strains and fewer acetic acid bacteria strains live together in a natural matrix named “kefir grain”, which is formed from various proteins and polysaccharides. Different microbial species live together in slimy kefir grain and it has been thought that synergetic effect could take place between microorganisms, which belong to different genera and species. In this research, yeast and LAB were isolated from kefir samples obtained from Uludag University Food Engineering Department. The cell morphology of isolates was screened by microscopic examination. Gram reactions of bacteria isolates were determined by Gram staining method, and as well catalase activity was examined. After observing the microscopic/morphological and physical, enzymatic properties of all isolates, they were divided into the groups as LAB and/or yeast according to their physicochemical responses to the applied examinations. As part of this research, the antagonistic/synergistic efficacy of the identified five LAB and five yeast strains to each other were determined individually by disk diffusion method. The antagonistic or synergistic effect is one of the most important properties in a co-culture system that different microorganisms are living together. The synergistic effect should be promoted, whereas the antagonistic effect is prevented to provide effective culture for fermentation of kefir. The aim of this study was to determine microbial interactions between identified yeast and LAB strains, and whether their effect is antagonistic or synergistic. Thus, if there is a strain which inhibits or retards the growth of other strains found in Kefir microflora, this circumstance shows the presence of antagonistic effect in the medium. Such negative influence should be prevented, whereas the microorganisms which have synergistic effect on each other should be promoted by combining them in kefir grain. Standardisation is the most desired property for industrial production. Each microorganism found in the microbial flora of a kefir grain should be identified individually. The members of the microbial community found in the glue-like kefir grain may be redesigned as a starter culture regarding efficacy of each microorganism to another in kefir processing. The main aim of this research was to shed light on more effective production of kefir grain and to contribute a standardisation of kefir processing in the food industry.

Keywords: antagonistic effect, kefir, lactic acid bacteria (LAB), synergistic, yeast

Procedia PDF Downloads 250
528 In Vitro Antioxidant and Free Radical Scavenging Activity of Phyllanthus Emblica L. Extract

Authors: Benyapa Suksuwan

Abstract:

Introduction: Oxidative stress is identified as the root cause of the development and progression of several diseases as the disproportion of free radicals in the body leads to tissue or cell damage. Polyphenols are the most common antioxidant found in plants and are efficient in capturing oxidative free radicals. Aim of the Study: This study focused on the antioxidant activity of polyphenols extracted from Phyllanthus Emblica L. as oxidative stress plays a vital role in developing and progressing many diseases, including cardiovascular diseases and cancer. Materials and Methods: The plant was extracted using a mixture solvent (ethyl alcohol: water in ratio 8:2). The total phenolic content of P. Emblica extract was determined using the Folin-Cioucalteu method and calculated as gallic acid equivalents (GAE) and various antioxidant assays DPPH and ABTS radical scavenging capacity assays. Results and Discussion: The findings exhibited a strong correlation between antioxidant activity and the total phenol contents. In addition, the IC₅₀ of P. Emblica extract via DPPH and ABTS assays were 68.10 μg/mL ± 0.455, and 49.24 μg/mL ± 0.716, respectively. Furthermore, P. Emblica extract showed antioxidant activities in a concentration-dependent manner. Vitamin C was used as a positive control in the DPPH assay, while Trolox was used as a positive control in the ABTS assay. Conclusions: In conclusion, P. Emblica extract consisted of a high amount of total phenolic content, which possesses potent antioxidant activity. However, further antioxidant activity assays using human cell lines such as SOD, ROS, and RNS scavenging assays and in vitro antioxidant experiments should be performed in order.

Keywords: antioxidant, ABTS scavenging, DPPH scavenging assay, total phenol contents assay, Phyllanthus Emblica L

Procedia PDF Downloads 173
527 Search of Сompounds with Antimicrobial and Antifungal Activity in the Series of 1-(2-(1H-Tetrazol-5-yl)-R1-phenyl)-3-R2-phenyl(ethyl)ureas

Authors: O. Antypenko, I. Vasilieva, S. Kovalenko

Abstract:

Investigations for new effective and less toxic antimicrobials agents are always up-to-date. The tetrazole derivatives are quite interesting objects as for synthesis as well as for pharmacological screening. Thus, some derivatives of tetrazole demonstrated antimicrobial activity, namely 5-phenyl-tetrazolo[1,5-c]quinazoline was effective one against Staphylococcus aureus and Esherichia faecalis (MIC = 250 mg/L). Besides, investigation of the 9-bromo(chloro)-5-morpholin(piperidine)-4-yl-tetrazolo[1,5-c]quinazoline’s antimicrobial activity against Esherichia coli and Enterococcus faecalis, Pseudomonas aeruginosa and Staphylococcus aureus revealed that sensitivity of Gram-positive bacteria to the compounds was higher than that of Gram-negative bacteria. So, our previously synthesized, 31 derivatives of 1-(2-(1H-tetrazol-5-yl)-R1-phenyl)-3-R2-phenyl(ethyl)ureas were decided to test for their in vitro antibacterial activity against Gram-positive bacteria (Staphylococcus aureus ATCC 25923, Enterobacter aerogenes, Enterococcus faecalis ATCC 29212), Gram-negative bacteria (Pseudomonas aeruginosa ATCC 9027, Escherichia coli ATCC 25922, Klebsiella pneumoniae 68) and antifungal properties against Candida albicans ATCC 885653. Agar-diffusion method was used for determination of the preliminary activity compared to well-known reference antimicrobials. All the compounds were dissolved in DMSO at a concentration of 100 μg/disk, using inhibition zone diameter (IZD, mm) as a measure for the antimicrobial activity. The most active turned to be 3 structures, that inhibited several bacterial strains: 1-ethyl-3-(5-fluoro-2-(1H-tetrazol-5-yl)phenyl)urea (1), 1-(4-bromo-2-(1H-tetrazol-5-yl)-phenyl)-3-(4-(trifluoromethyl)phenyl)urea (2) and 1-(4-chloro-2-(1H-tetrazol-5-yl)phenyl)-3-(3-(trifluoromethyl)phenyl)urea (3). IZM (mm) was 40 (Escherichia coli), 25 (Klebsiella pneumonia) for compound 1; 12 (Pseudomonas aeruginosa), 15 (Staphylococcus aureus), 10 (Enterococcus faecalis) for compound 2; 25 (Staphylococcus aureus), 15 (Enterococcus faecalis) for compound 3. The most sensitive to the activity of the substances were Gram-negative bacteria Pseudomonas aeruginosa. While none of compound effected on Candida albicans. Speaking about, reference drugs: Amikacin (30 µg/disk) showed 27 and Ceftazide (30 µg/disk) 25 against Pseudomonas aeruginosa. That is, unfortunately, higher than studied 1-(2-(1H-tetrazol-5-yl)-R1-phenyl)-3-R2-phenyl(ethyl)ureas. Obtained results will be used for further purposeful optimization of the leading compounds in the more effective antimicrobials because of the ever-mounting problem of microorganism’s resistance.

Keywords: antimicrobial, antifungal, compounds, 1-(2-(1H-tetrazol-5-yl)-R1-phenyl)-3-R2-phenyl(ethyl)ureas

Procedia PDF Downloads 333
526 EcoMush: Mapping Sustainable Mushroom Production in Bangladesh

Authors: A. A. Sadia, A. Emdad, E. Hossain

Abstract:

The increasing importance of mushrooms as a source of nutrition, health benefits, and even potential cancer treatment has raised awareness of the impact of climate-sensitive variables on their cultivation. Factors like temperature, relative humidity, air quality, and substrate composition play pivotal roles in shaping mushroom growth, especially in Bangladesh. Oyster mushrooms, a commonly cultivated variety in this region, are particularly vulnerable to climate fluctuations. This research explores the climatic dynamics affecting oyster mushroom cultivation and, presents an approach to address these challenges and provides tangible solutions to fortify the agro-economy, ensure food security, and promote the sustainability of this crucial food source. Using climate and production data, this study evaluates the performance of three clustering algorithms -KMeans, OPTICS, and BIRCH- based on various quality metrics. While each algorithm demonstrates specific strengths, the findings provide insights into their effectiveness for this specific dataset. The results yield essential information, pinpointing the optimal temperature range of 13°C-22°C, the unfavorable temperature threshold of 28°C and above, and the ideal relative humidity range of 75-85% with the suitable production regions in three different seasons: Kharif-1, 2, and Robi. Additionally, a user-friendly web application is developed to support mushroom farmers in making well-informed decisions about their cultivation practices. This platform offers valuable insights into the most advantageous periods for oyster mushroom farming, with the overarching goal of enhancing the efficiency and profitability of mushroom farming.

Keywords: climate variability, mushroom cultivation, clustering techniques, food security, sustainability, web-application

Procedia PDF Downloads 28
525 Green Synthesis and Characterisation of Gold Nanoparticles from the Stem Bark and Leaves of Khaya Senegalensis and Its Cytotoxicity on MCF7 Cell Lines

Authors: Stephen Daniel Iduh, Evans Chidi Egwin, Oluwatosin Kudirat Shittu

Abstract:

The process for the development of reliable and eco-friendly metallic Nanoparticles is an important step in the field of Nanotechnology for biomedical application. To achieve this, use of natural sources like biological systems becomes essential. In the present work, extracellular biosynthesis of gold Nanoparticles using aqueous leave and stembark extracts of K. senegalensis has been attempted. The gold Nanoparticles produced were characterized using High Resolution scanning electron microscopy, Ultra Violet–Visible spectroscopy, zeta-sizer Nano, Energy-Dispersive X-ray (EDAX) Spectroscopy and Fourier Transmission Infrared (FTIR) Spectroscopy. The cytotoxicity of the synthesized gold nanoparticles on MCF-7 cell line was evaluated using MTT assay. The result showed a rapid development of Nano size and shaped particles within 5 minutes of reaction with Surface Plasmon Resonance at 520 and 525nm respectively. An average particle size of 20-90nm was confirmed. The amount of the extracts determines the core size of the AuNPs. The core size of the AuNPs decreases as the amount of extract increases and it causes the shift of Surface Plasmon Resonance band. The FTIR confirms the presence of biomolecules serving as reducing and capping agents on the synthesised gold nanoparticles. The MTT assay shows a significant effect of gold nanoparticles which is concentration dependent. This environment-friendly method of biological gold Nanoparticle synthesis has the potential and can be directly applied in cancer therapy.

Keywords: biosynthesis, gold nanoparticles, characterization, calotropis procera, cytotoxicity

Procedia PDF Downloads 457
524 Bacteremia Caused by Nontoxigenic Vibrio cholerae in an Immunocompromised Patient in Istanbul, Turkey

Authors: Fatma Koksal Çakirlar, Si̇nem Ozdemir, Selcan Akyol, Revazi̇ye Gulesen, Murat Gunaydin, Nevri̇ye Gonullu, Belkis Levent, Nuri̇ Kiraz

Abstract:

Vibrio cholerae O1 and O139 are the causative agent of epidemic or pandemic cholera. V. cholerae O1 is generally accepted as a non-invasive enterotoxigenic organism causing gastroenteritis of various severities. Non-O1 V. cholerae can cause small outbreaks of diarrhea due to consumption of contaminated food and water. Particularly, the patients with achlorydria have a risk for vibrio infections. There are numerous case reports of bacteremia caused by vibrio in patients with predisposing conditions like cirrhosis, nephrotic syndrome, diabetes, hematologic malignancy, gastrectomy, and AIDS. We described in this study the first case of nontoxigenic, non-01/non-O139 V. cholerae isolated from the blood culture of a 77-year-old female patient with hipertension, diabetes, coronary artery disease, gout and about 9 years ago migrated breast cancer history. The patient with complaints of shortness of breath, fever and malaise admitted to our emergency clinic were evaluated. There was no diarrhea or abdominal symptoms in the patient. No growth in her urine culture, but blood culture (BACTEC 9120 system, Becton Dickinson, USA) was positive for non-01/non-O139 V. cholerae that was identified by conventional methods and Phoenix automated system (BD Diagnostic Systems, Sparks, MD). It does not secrete the cholera toxin. The agglutination test was negative with polyvalent O1 antisera and O139 antiserum. Empirically ceftriaxone was administered to the patient and she was discharged with improvement in general condition. In this study we report bacteremia by non-01/non-O139 V. cholerae that is rare in the worldwide and first in Turkey.

Keywords: bacteremia, blood culture, immunocompromised patient, Non-O1 vibrio cholerae

Procedia PDF Downloads 190
523 Development and Pre-clinical Evaluation of New ⁶⁴Cu-NOTA-Folate Conjugates for PET Imaging of Folate Receptor-Positive Tumors

Authors: Norah Al Hokbany, Ibrahim Al Jammaz, Basem Al Otaibi, Yousif Al Malki, Subhani M. Okarvi

Abstract:

Objective: The folate receptor is over-expressed in a wide variety of human tumors. Conjugates of folate have been shown to be selectively taken up by tumor cells via the folate receptor. In an attempt to develop new folate radiotracers with favorable biochemical properties for detecting folate receptor-positive cancers. Methods: we synthesized ⁶⁴Cu-NOTA- and ⁶⁴Cu-NOTAM-folate conjugates using a straightforward and simple one-step reaction. Radiochemical yields were greater than 95% (decay-corrected) with a total synthesis time of less than 20 min. Results: Radiochemical purities were always greater than 98% without high-performance liquid chromatography (HPLC) purification. These synthetic approaches hold considerable promise as a rapid and simple method for ⁶⁴Cu-folate conjugate preparation with high radiochemical yield in a short synthesis time. In vitro tests on the KB cell line showed that significant amounts of the radio conjugates were associated with cell fractions. Bio-distribution studies in nude mice bearing human KB xenografts demonstrated a significant tumor uptake and favorable bio-distribution profile for ⁶⁴Cu-NOTA- and ⁶⁴Cu-NOTAM-folate conjugate. The uptake in the tumors was blocked by the excess injection of folic acid, suggesting a receptor-mediated process. Conclusion: These results demonstrate that the ⁶⁴Cu-NOTAM-folate conjugate may be useful as a molecular probe for the detection and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis, as well as monitoring tumor response to treatment.

Keywords: folate, receptor, tumor imaging, ⁶⁴Cu-NOTA-folate, PET

Procedia PDF Downloads 81
522 Insufficient Sleep as a Risk Factor for Substance Use Among Adolescents: The Mediating Role of Depressive Symptoms

Authors: Aaron Kim, Nydia Hernandez

Abstract:

Despite the known deficits in sleep duration among adolescents and the increasing prevalence of substance use behaviors among this group, relatively little is known about how insufficient sleep is related to various substance use behaviors and the underlying mechanisms. Informed by the literature suggesting the predictive role of insufficient sleep for substance use and depressive symptoms, we hypothesized that adolescents who lack sufficient sleep during school nights would report a higher level of depressive symptoms and substance use than their counterparts with sufficient sleep. We also hypothesized that depressive symptoms would explain the association of insufficient sleep with substance use, suggesting that mental health plays an important role as a mechanism between insufficient sleep and substance use. This study used the data drawn from the 2019 Youth Risk Behavior Surveillance System Data, which includes a nationally representative sample of U.S. high school students (N=13,677, 49.4% Female, 9th-12th graders). Self-report measures of insufficient sleep (sleeping<7 h on an average school night), depressive symptoms (yes/no), any past 30-day use of cigarette (yes/no), e-cigarette (yes/no), alcohol (yes/no), and marijuana (yes/no). Among the total sample, 47.9% of students reported that they did not have sufficient sleep on school nights, indicating sleeping less than 7 hours. Regarding depressive symptoms, 36.7% of students reported feeling sad or hopeless almost every day for two weeks or more in a row during the past 12 months. Also, the percentages of students who reported one or more times of cigarette use, e-cigarette use, alcohol use, and marijuana use in the past month were 5.32%, 30.11%, 26.83%, and 21.65%, respectively. For bivariate associations among these study variables, insufficient sleep was positively associated with other variables: depressive symptoms (r=.08, p<.001), cigarette use (r=.03, p<.001), e-cigarette use (r=.04, p<.001), alcohol use (r=.07, p<.001), and marijuana use (r=.08, p<.001). After controlling for students’ characteristics (i.e., age, gender, race/ethnicity, grades), sleeping less than 7 hours on school nights (vs. sleeping more than 7 hours) was significantly associated with the past 30-day use of alcohol and marijuana, whereas cigarette and e-cigarette uses were not. That is, the students who reported having an insufficient sleep on school nights had higher odds of alcohol (Odds Ratio [OR]=1.15, 95% Confidence Interval [CI]=1.014-1.301) and marijuana use (OR=1.36, 95% CI=1.132-1.543). In a subsequent analysis including depressive symptoms together with insufficient sleep, the association of insufficient sleep with alcohol use (OR=1.13, 95% CI=1.011-1.297) and marijuana use (OR=1.33, 95% CI=1.130-1.521) were attenuated and explained by depressive symptoms. Depressive symptoms significantly increased the odds of alcohol use by 32.2% (OR=1.32, 95% CI=1.131-1.557) and marijuana use by 202.1% (OR=2.02, 95% CI=1.672-2.502). These findings together suggest that insufficient sleep may contribute to increased risks of substance uses among adolescents. The current study also shows that psychological disorders of adolescents play important roles in understanding the association between insufficient sleep and substance use, suggesting insufficient sleep is related to substance use indirectly through depressive symptoms. This study indicates the importance of sleep deprivation among adolescents and screening for insufficient sleep in preventing/intervening in substance use.

Keywords: adolescents, depressive symptoms, sleep, substance use

Procedia PDF Downloads 77
521 Ochratoxin-A in Traditional Meat Products from Croatian Households

Authors: Jelka Pleadin, Nina Kudumija, Ana Vulic, Manuela Zadravec, Tina Lesic, Mario Skrivanko, Irena Perkovic, Nada Vahcic

Abstract:

Products of animal origin, such as meat and meat products, can contribute to human mycotoxins’ intake coming as a result of either indirect transfer from farm animals exposed to naturally contaminated grains and feed (carry-over effects) or direct contamination with moulds or naturally contaminated spice mixtures used in meat production. Ochratoxin A (OTA) is mycotoxin considered to be of the outermost importance from the public health standpoint in connection with meat products. The aim of this study was to investigate the occurrence of OTA in different traditional meat products circulating on Croatian markets during 2018, produced by a large number of households situated in eastern and north Croatian regions using a variety of technologies. Concentrations of OTA were determined in traditional meat products (n = 70), including dry fermented sausages (Slavonian kulen, Slavonian sausage, Istrian sausage and domestic sausage; n = 28), dry-cured meat products (pancetta, pork rack and ham; n = 22) and cooked sausages (liver sausages, black pudding sausages and pate; n = 20). OTA was analyzed by use of quantitative screening immunoassay method (ELISA) and confirmed for positive samples (higher than the limit of detection) by liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Whereas the bacon samples contaminated with OTA were not found, its level in dry fermented sausages ranged from 0.22 to 2.17 µg/kg and in dry-cured meat products from 0.47 to 5.35 µg/kg, with in total 9% of positive samples. Besides possible primary contamination of these products arising due to improper manufacturing or/and storage conditions, observed OTA contamination could also be the consequence of secondary contamination that comes as a result of contaminated feed the animals were fed on. OTA levels obtained in cooked sausages ranged from 0.32 to 4.12 µg/kg (5% of positives) and could probably be linked to the contaminated raw materials (liver, kidney and spices) used in the sausages production. The results showed an occasional OTA contamination of traditional meat products, pointing that to avoid such contamination on households these products should be produced and processed under standardized and well-controlled conditions. Further investigations should be performed in order to identify mycotoxin-producing moulds on the surface of the products and to define preventative measures that can reduce the contamination of traditional meat products during their production on households and period of storage.

Keywords: Croatian households, ochratoxin-A, traditional cooked sausages, traditional dry-cured meat products

Procedia PDF Downloads 150
520 Effect of Methanol Root Extracts of Moringa Oleifera on Lipid Profile Parameters, Atherogenic Indices and HMG – CoA Reductase Activities of Poloxamer 407-Induced Hyperlipidemic Rats

Authors: Matthew Ocheleka Itodo, Ogo Agbo Ogo, Agnes Ogbene Abutu, Bawa Inalegwu

Abstract:

Hyperlipidemia is characterised by elevated serum total cholesterol and low density and very low-density lipoprotein cholesterol and decreased high-density lipoprotein are the risk factor for coronary heart diseases. There are claims by traditional medicine practitioners in Nigeria that Moringa oleifera plants are used for the treatment of cardiovascular diseases, but it appears there is no scientific research and, publication or documented work to verify these claims. This study aimed to determine the effect of methanol root extracts of Moringa oleifera on Lipid profile, Atherogenic indices and 3 hydroxyl 3 methylglutaryl Coenzyme A reductase activity of poloxamer 407-induced hyperlipidemic rats. The animals were grouped into 8; Group 1: Normal control, Group 2: Hyperlipidemic control. Groups 2 to 8 were induced with Poloxamer 407 1000 mg/Kg body weight. However, group 3 were treated with standard drugs (atorvastatin). Group 4 was treated with crude extract, and groups 5 to 8 were treated with purified fractions from column chromatography. The preliminary antihyperlipidemic study showed Methanol root extract at 200 mg/kg body weight significantly (p≤0.05) decreased total cholesterol, low-density lipoprotein, triacylglyceride, 3 hydroxyls 3 methylglutaryl Coenzyme A reductase, and increase high-density lipoprotein of hyperlipidemic treated groups. Screening the extracts for the most potent anti-hyperlipidemic activity reveals that fraction 1 of Total Cholesterol and Fraction 3 of Triacylglyceride have the highest percentage reduction of 56% and 51%, respectively. The atherogenic risk factor of all induced treated rats shows a significant (p<0.05) decrease in levels of Castelli’s risk index II, atherogenic index of plasma and a significant (p<0.05) higher level of Castelli’s risk index I ratio. The study shows that the methanol extract of root possesses antihyperlipidemic effects and may explain why it has been found to be useful in the management of cardiovascular diseases by traditional medicine practitioners.

Keywords: hyperlipidemia, moringa oleifera, poloxamer 407, lipid profile

Procedia PDF Downloads 39
519 Plasma Engineered Nanorough Substrates for Stem Cells in vitro Culture

Authors: Melanie Macgregor-Ramiasa, Isabel Hopp, Patricia Murray, Krasimir Vasilev

Abstract:

Stem cells based therapies are one of the greatest promises of new-age medicine due to their potential to help curing most dreaded conditions such as cancer, diabetes and even auto-immune disease. However, establishing suitable in vitro culture materials allowing to control the fate of stem cells remain a challenge. Amongst the factor influencing stem cell behavior, substrate chemistry and nanotopogaphy are particularly critical. In this work, we used plasma assisted surface modification methods to produce model substrates with tailored nanotopography and controlled chemistry. Three different sizes of gold nanoparticles were bound to amine rich plasma polymer layers to produce homogeneous and gradient surface nanotopographies. The outer chemistry of the substrate was kept constant for all substrates by depositing a thin layer of our patented biocompatible polyoxazoline plasma polymer on top of the nanofeatures. For the first time, protein adsorption and stem cell behaviour (mouse kidney stem cells and mesenchymal stem cells) were evaluated on nanorough plasma deposited polyoxazoline thin films. Compared to other nitrogen rich coatings, polyoxazoline plasma polymer supports the covalent binding of proteins. Moderate surface nanoroughness, in both size and density, triggers cell proliferation. In association with polyoxazoline coating, cell proliferation is further enhanced on nanorough substrates. Results are discussed in term of substrates wetting properties. These findings provide valuable insights on the mechanisms governing the interactions between stem cells and their growth support.

Keywords: nanotopography, stem cells, differentiation, plasma polymer, oxazoline, gold nanoparticles

Procedia PDF Downloads 245
518 Phytochemical Screening and Assessment of Hepatoprotective Activity of Geigeria alata Leaves Ethanolic Extract on Wistar Rats

Authors: Girgis Younan, Ikram Eltayeb

Abstract:

Geigeria alata belongs to the family Asteraceae, is an effective plant traditionally used in Sudan as a therapy for hepatic disease and as an antiepileptic, antispasmodic and to treat cough and intestinal complaints.The liver is responsible for many critical functions within the body and any liver disease or injury will result in the loss of those functions leading to significant damage in the body. Liver diseases cause increase in liver enzymes (AST, ALP ALT) and total bilirubin and a decrease in total blood protein level. The objective of this study is to investigate the hepato-protective activity of Geigeria alata leaves ethanolic extract. The plant leaves were extracted using 96% ethanol using Soxhlet apparatus. The hepatoprotective effect was determined using 25 wistar rats, the rats was divided to 5 groups, each group contain 5 rats: [Normal control group] receiving purified water, liver damage was induced in wistar rats by administering a 1:1 (v/v) mixture of CCl4 (1.25 ml/kg) and olive oil once at day four of the experiment [negative control group]. Two doses of extract [400mg/kg and 200mg/kg] was applied daily for 7 days, and standard drug Silymarin (200 mg/kg) were administered daily for 7 days to CCl4-treated rats. The degree of hepato-protective activity was evaluated by determining the hepatic marker enzymes AST, ALP, ALT, total Bilirubin and total proteins (TP). Results have shown that, the extract of G.alata leaves reduced the level of liver enzymes ALT, AST, ALP, total bilirubin and increased the level of total proteins. Since the levels of liver enzymes; bilirubin and total protein are considered as markers of liver function, the extract has proven to reduce the detrimental effects of liver toxicity induced using CCl4. The hepato-protective effect of extract on liver was found to be dose dependent, where the 400mg/kg dose of the extract exhibited higher activity than 200mg/kg dose. In addition, the effect of the higher dose (400mg/kg) of the extract was found to be higher than Silymarin standard drug. The result concludes that, G.alata leaves extract was found to exhibit profound hepato-protective activity, which justifies the traditional use of the plant for the treatment of hepatic diseases.

Keywords: alata, extract, geigeria, hepatoprotective

Procedia PDF Downloads 199
517 Nutrition, Dental Status and Post-Traumatic Stress Disorder among Underage Refugees in Germany

Authors: Marios Loucas, Rafael Loucas, Oliver Muensterer

Abstract:

Aim of the Study: Over the last two years, there has been a substantial rise of refugees entering Germany, of which approximately one-third are underage. Little is known about the general state of health such as nutrition, dental status and post-traumatic stress disorder among underage refugees. Our study assesses the general health status of underage refugees based on a large sample cohort. Methods: After ethics board approval, we used a structured questionnaire to collect demographic information and health-related elements in 3 large refugee accommodation centers, focusing on nutritional and dental status, as well as symptoms of posttraumatic stress disorder. Main results: A total of 461 minor refugees were included. The majority were boys (54.5%), average age was 8 years. Out of the 8 recorded countries of origin, most children came from Syria (33.6%), followed by Afghanistan (23.2%). Of the participants, 50.3% reported DSM-5 criteria of Posttraumatic stress disorder and presented mental health-related problems. The most frequently reported mental abnormalities were concentration disturbances (15.2%), sleep disorders (6.9%), unclear headaches (5.4%). The majority of the participants showed an unfavorable nutritional and dental status. According to the family, the majority of the children rarely eat healthy foods such as fruits, vegetables and fish. However, the majority of these children (over 90%) consume a large quantity of sugary foods and sweetened drinks such as soft drinks and confectionery at least daily. Caries was found in 63% of the minor children included in the study. A large proportion (47%) reported never brushing their teeth. According to the family, 78.3% of refugee children have never been evaluated by a dentist in Germany. The remainder visited a dentist mainly because of unbearable toothache. Conclusions: Minor refugees have specific psychological, nutritional and dental problems that must be considered in order to ensure appropriate medical care. Posttraumatic stress disorder is mainly caused by physical and emotional trauma suffered either during the flight or in the refugee camp in Germany. These data call for widespread screening of psychological, dental and nutritional problems in underage refugees. Dental care of this cohort is completely inadequate. Nutritional programs should focus on educating the families and providing the means to obtain healthy foods for these children.

Keywords: children, nutrition, posttraumatic stress disorder, refugee

Procedia PDF Downloads 145
516 Virtual Screening and in Silico Toxicity Property Prediction of Compounds against Mycobacterium tuberculosis Lipoate Protein Ligase B (LipB)

Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

Abstract:

The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.

Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT

Procedia PDF Downloads 388
515 LGR5 and Downstream Intracellular Signaling Proteins Play Critical Roles in the Cell Proliferation of Neuroblastoma, Meningioma and Pituitary Adenoma

Authors: Jin Hwan Cheong, Mina Hwang, Myung Hoon Han, Je Il Ryu, Young ha Oh, Seong Ho Koh, Wu Duck Won, Byung Jin Ha

Abstract:

Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) has been reported to play critical roles in the proliferation of various cancer cells. However, the roles of LGR5 in brain tumors and the specific intracellular signaling proteins directly associated with it remain unknown. Expression of LGR5 was first measured in normal brain tissue, meningioma, and pituitary adenoma of humans. To identify the downstream signaling pathways of LGR5, siRNA-mediated knockdown of LGR5 was performed in SH-SY5Y neuroblastoma cells followed by proteomics analysis with 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE). In addition, the expression of LGR5-associated proteins was evaluated in LGR5-inꠓhibited neuroblastoma cells and in human normal brain, meningioma, and pituitary adenoma tissue. Proteomics analysis showed 12 protein spots were significantly different in expression level (more than two-fold change) and subsequently identified by peptide mass fingerprinting. A protein association network was constructed from the 12 identified proteins altered by LGR5 knockdown. Direct and indirect interactions were identified among the 12 proteins. HSP 90-beta was one of the proteins whose expression was altered by LGR5 knockdown. Likewise, we observed decreased expression of proteins in the hnRNP subfamily following LGR5 knockdown. In addition, we have for the first time identified significantly higher hnRNP family expression in meningioma and pituitary adenoma compared to normal brain tissue. Taken together, LGR5 and its downstream sigꠓnaling play critical roles in neuroblastoma and brain tumors such as meningioma and pituitary adenoma.

Keywords: LGR5, neuroblastoma, meningioma, pituitary adenoma, hnRNP

Procedia PDF Downloads 20
514 Frequency of Problem Drinking and Depression in Males with a History of Alcohol Consumption Admitted to a Tertiary Care Setting in Southern Sri Lanka

Authors: N. H. D. P. Fonseka, I. H. Rajapakse, A. S. Dissanayake

Abstract:

Background: Problem drinking, namely alcohol dependence (AD) and alcohol abuse (AA) are associated with major medical, social and economic adverse consequences. Problem drinking behavior is noted among those admitted to hospitals due to alcohol-related medical/surgical complaints as well as those with unrelated complaints. Literature shows an association between alcohol consumption and depression. Aims of this study were to determine the frequency of problem drinking and depression among males with a history of alcohol consumption tertiary care setting in Southern Sri Lanka. Method: Two-hundred male patients who consumed alcohol, receiving care in medical and surgical wards in Teaching Hospital Galle, were assessed. A validated J12 questionnaire of the Mini International Neuropsychiatric Interview was administered to determine frequency AA and AD. A validated PHQ 9 questionnaire to determine the prevalence and severity of depression. Results: Sixty-three participants (31%) had problem drinking. Of them, 61% had AD, and 39% had AA. Depression was noted in 39 (19%) subjects. In those who reported alcohol consumption not amounting to problem drinking, depression was noted in 23 (16%) participants. Mild depression was seen in 17, moderate in five and moderately severe in one. Among those who had problem drinking, 16 (25%) had depression. Mild depression was seen in four, moderate in seven, moderately severe in three and severe in two. Conclusions: A high proportion alcohol users had problem drinking. Adverse consequences associated with problem drinking places a major strain on the health system especially in a low resource setting where healthcare spending is limited and alcohol cessation support services are not well organised. Thus alcohol consumption and problem drinking behaviour need to be inquired into all medical consultations. Community prevalence of depression in Sri Lanka is approximately 10%. Depression among those consuming alcohol was two times higher compared to the general population. The rates of depression among those with problem drinking were especially high being 2.5 times more common than in the general population. A substantial proportion of these patients with depression had moderately severe or severe depression. When depression coexists with problem drinking, it may increase the tendency to consume alcohol as well as act as a barrier to the success of alcohol cessation interventions. Thus screening all patients who consume alcohol for depression, especially those who are problem drinkers becomes an important step in their clinical evaluation. In addition, in view of the high prevalence of problem drinking and coexistent depression, the need to organize a structured alcohol cessation support service in Sri Lanka as well as the need for increasing access to psychological evaluation and treatment of those with problem drinking are highlighted.

Keywords: alcohol abuse, alcohol, depression, problem drinking

Procedia PDF Downloads 132
513 Construction Noise Control: Hong Kong Reviews International Best Practices

Authors: Morgan Cheng, Wilson Ho, Max Yiu, Dragon Tsui, Wylog Wong, Richard Kwan, K. C. Lam, Hannah Lo, C. L. Wong

Abstract:

Hong Kong has been known worldwide for its ability to thrive under trying circumstances. The 7.5 million residents of this mature and busy metropolis are living in a primarily high-rise city whereby development and renewal of the cityscape are taking place unceasingly. Hong Kong residents are therefore affected by the virtually continuous and numerous construction activities. In 2020, the Hong Kong environmental protection department (EPD) completed a feasibility study on managing construction noise, including those associated with the renovation of domestic premises. Part of the study was the review of management and control of construction noise in other metropolitan cities globally. As far as the authors are aware of, such worldwide and extensive review of best practices on construction noise control has not been conducted for over 20 years. In order to benefit from international best practices, the extensive review is to identify possible areas for improvement in Hong Kong. The consultant of the study first referred to the United Nations Report ‘The World’s Cities in 2016’ and examined the top 100 cities therein. The 20 most suitable cities were then chosen for further review. Upon screening of each of these 20 cities, 12 cities with the more relevant management practices were selected for further scrutiny. These 12 cities were: Asia – Tokyo, Seoul, Taipei, Guangzhou, Singapore; Europe – City of Westminster (London), Berlin; North America – Toronto, New York City, San Francisco; Oceania – Sydney, Melbourne. Afterwards, three cities, namely Sydney, City of Westminster, and New York City, were selected for in-depth review. These cities were chosen primarily because of the maturity, success, and effectiveness of their construction noise management and control measures, as well as their similarity to Hong Kong in key and selected aspects. One of the more important findings of the review is the usefulness of early focus, with the aim of designing the noise issues away wherever practicable. The consultant examined the similar yet different construction noise early focus mechanisms of the three cities. This paper describes this landmark worldwide and extensive review of international best practices on construction noise management and control. The methodology, approach, and key findings are presented to give readers a succinct yet comprehensive view. The authors shared the findings with the acoustics professionals worldwide with the hope of global advancement of more mature construction noise management while welcoming sustainable development and construction.

Keywords: construction noise, international best practices, noise control, noise management

Procedia PDF Downloads 112
512 Sustainable Model of Outreach Eye Camps: A Case Study from Reputed Eye Hospital of Central India

Authors: Subramanyam Devarakonda Hanumantharao, Udayendu Prakash Sharma, Mahesh Garg

Abstract:

Introduction: Gomabai Netralaya a reputed eye hospital is located in Neemuch a small city of Madhya Pradesh, India. The hospital is established in 1992 by Late. G.D Agrawal a renowned educationist, freedom fighter and philanthropist. The eye hospital was established to serve all sections of the society in affordable manner. To provide comprehensive eye care services to the rural poor the hospital started organizing outreach camps since 1994. Purpose: To study the cost effectiveness of outreach eye camps for addressing the sustainability issues of the outreach program. Methods: One year statistics of outreach eye camps were collected from Hospital Management Information System software to analyze the productivity of camps. Income and expenses report was collected from outreach department records to analyze per camp expenses and per patient expenses against the income generated. All current year records were analyzed to have accuracy of information and results. Information was collected in two ways: 1)Actual camp performance records and expenses from book of accounts. 2)Cross verification was done through one to one discussion with outreach staff. Results: Total 17534 outpatients were examined through 52 outreach eye camps. Total 6042 (34% of total outpatients) patients were advised with cataracts and 4651 (77% of advice) operations were performed. The average OPD per camp was 337 and per camp 116 patients was advised for cataract surgery and 89 surgeries were performed per camp. Total 18200 US$ incurred on organizing 52 outreach camps in the radius of 100 k.ms. Considering the total outpatients screened through camps the screening cost per patient was 1.00 US$ and considering the surgical output the per surgery expenses was 4.00 US$. The cost recovery of the total expenses was through Government grant of US$ 16.00 per surgery (that includes surgical grant). All logistics cost of camps and patients transportation cost was taken care by local donors. Conclusion: The present study demonstrates that with people’s participation, successful high volume outreach eye camps can be organized. The cost effectiveness of the outreach camps is totally depended on volume of outpatient’s turn-up at camp site and per camp surgical output. The only solution to sustainability of outreach eye camps is sharing of cost with local donors and increasing productivity.

Keywords: camps, outreach, productivity, sustainable

Procedia PDF Downloads 142
511 Detection Kit of Type 1 Diabetes Mellitus with Autoimmune Marker GAD65 (Glutamic Acid Decarboxylase)

Authors: Aulanni’am Aulanni’am

Abstract:

Incidence of Diabetes Mellitus (DM) progressively increasing it became a serious problem in Indonesia and it is a disease that government is priority to be addressed. The longer a person is suffering from diabetes the more likely to develop complications particularly diabetic patients who are not well maintained. Therefore, Incidence of Diabetes Mellitus needs to be done in the early diagnosis of pre-phase of the disease. In this pre-phase disease, already happening destruction of pancreatic beta cells and declining in beta cell function and the sign autoimmunity reactions associated with beta cell destruction. Type 1 DM is a multifactorial disease triggered by genetic and environmental factors, which leads to the destruction of pancreatic beta cells. Early marker of "beta cell autoreactivity" is the synthesis of autoantibodies against 65-kDa protein, which can be a molecule that can be detected early in the disease pathomechanism. The importance of early diagnosis of diabetic patients held in the phase of pre-disease is to determine the progression towards the onset of pancreatic beta cell destruction and take precautions. However, the price for this examination is very expensive ($ 150/ test), the anti-GAD65 abs examination cannot be carried out routinely in most or even in all laboratories in Indonesia. Therefore, production-based Rapid Test Recombinant Human Protein GAD65 with "Reverse Flow Immunchromatography Technique" in Indonesia is believed to reduce costs and improve the quality of care of patients with diabetes in Indonesia. Rapid Test Product innovation is very simple and suitable for screening and routine inspection of GAD65 autoantibodies. In the blood serum of patients with diabetes caused by autoimmunity, autoantibody-GAD65 is a major serologic marker to detect autoimmune reaction because their concentration level of stability.GAD65 autoantibodies can be found 10 years before clinical symptoms of diabetes. Early diagnosis is more focused to detect the presence autontibodi-GAD65 given specification and high sensitivity. Autoantibodies- GAD65 that circulates in the blood is a major indicator of the destruction of the islet cells of the pancreas. Results of research in collaboration with Biofarma has produced GAD65 autoantibodies based Rapid Test had conducted the soft launch of products and has been tested with the results of a sensitivity of 100 percent and a specificity between 90 and 96% compared with the gold standard (import product) which worked based on ELISA method.

Keywords: diabetes mellitus, GAD65 autoantibodies, rapid test, sensitivity, specificity

Procedia PDF Downloads 235