Search results for: drug targeting
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2540

Search results for: drug targeting

1310 Parallel Self Organizing Neural Network Based Estimation of Archie’s Parameters and Water Saturation in Sandstone Reservoir

Authors: G. M. Hamada, A. A. Al-Gathe, A. M. Al-Khudafi

Abstract:

Determination of water saturation in sandstone is a vital question to determine the initial oil or gas in place in reservoir rocks. Water saturation determination using electrical measurements is mainly on Archie’s formula. Consequently accuracy of Archie’s formula parameters affects water saturation values rigorously. Determination of Archie’s parameters a, m, and n is proceeded by three conventional techniques, Core Archie-Parameter Estimation (CAPE) and 3-D. This work introduces the hybrid system of parallel self-organizing neural network (PSONN) targeting accepted values of Archie’s parameters and, consequently, reliable water saturation values. This work focuses on Archie’s parameters determination techniques; conventional technique, CAPE technique, and 3-D technique, and then the calculation of water saturation using current. Using the same data, a hybrid parallel self-organizing neural network (PSONN) algorithm is used to estimate Archie’s parameters and predict water saturation. Results have shown that estimated Arche’s parameters m, a, and n are highly accepted with statistical analysis, indicating that the PSONN model has a lower statistical error and higher correlation coefficient. This study was conducted using a high number of measurement points for 144 core plugs from a sandstone reservoir. PSONN algorithm can provide reliable water saturation values, and it can supplement or even replace the conventional techniques to determine Archie’s parameters and thereby calculate water saturation profiles.

Keywords: water saturation, Archie’s parameters, artificial intelligence, PSONN, sandstone reservoir

Procedia PDF Downloads 125
1309 Data Mining Techniques for Anti-Money Laundering

Authors: M. Sai Veerendra

Abstract:

Today, money laundering (ML) poses a serious threat not only to financial institutions but also to the nation. This criminal activity is becoming more and more sophisticated and seems to have moved from the cliché of drug trafficking to financing terrorism and surely not forgetting personal gain. Most of the financial institutions internationally have been implementing anti-money laundering solutions (AML) to fight investment fraud activities. However, traditional investigative techniques consume numerous man-hours. Recently, data mining approaches have been developed and are considered as well-suited techniques for detecting ML activities. Within the scope of a collaboration project on developing a new data mining solution for AML Units in an international investment bank in Ireland, we survey recent data mining approaches for AML. In this paper, we present not only these approaches but also give an overview on the important factors in building data mining solutions for AML activities.

Keywords: data mining, clustering, money laundering, anti-money laundering solutions

Procedia PDF Downloads 531
1308 Traditional Phytotherapy among Tribes of Madhya Pradesh, India Used in the Treatment of Ear, Nose and Throat Disorders

Authors: Sumeet Dwivedi, Shweta Shriwas, Raghvendra Dubey

Abstract:

Madhya Pradesh, a Central State of India is rich in natural heritage due to tribal impact. Herbal harmony present either cultivated or by naturally being used by the tribes of the state in the treatment of several human and animal disorders. Diseases of ear, nose and throat (ENT) often have serious consequences including hearing impairment, and emotional strain that lower the quality of life of patients. Traditional phytotherapy have now been found to be instrumental in improving chances of discovering plants with antimicrobial activity in new drug development. The present paper enumerates the uses of ten herbs viz., garlic, eucalyptus, marigold, tulsi, euphorbia, lemon grass, haldi, bhringraj, ginger and ajwain. An attempt has also been made to reveal the method of preparation, dose, duration possible MOA of these herbs used for ENT disorders.

Keywords: ENT, traditional phytotherapy, herbs, Madhya Pradesh

Procedia PDF Downloads 245
1307 Effect of Hemicellulase on Extraction of Essential Oil from Algerian Artemisia campestris

Authors: Khalida Boutemak, Nasssima Benali, Nadji Moulai-Mostefa

Abstract:

Effect of enzyme on the yield and chemical composition of Artemisia campestris essential oil is reported in the present study. It was demonstrated that enzyme facilitated the extraction of essential oil with increase in oil yield and did not affect any noticeable change in flavour profile of the volatile oil. Essential oil was tested for antibacterial activity using Escherichia coli; which was extremely sensitive against control with the largest inhibition (29mm), whereas Staphylococcus aureus was the most sensitive against essential oil obtained from enzymatic pre-treatment with the largest inhibition zone (25mm). The antioxidant activity of the essential oil with hemicellulase pre-treatment (EO2) and control sample (EO1) was determined through reducing power. It was significantly lower than the standard drug (vitamin C) in this order: vitamin C˃EO2˃EO1.

Keywords: Artemisia campestris, enzyme pre-treatment, hemicellulase, antibacterial activity, antioxidant activity

Procedia PDF Downloads 326
1306 Method for Targeting Small Volume in Rat Brainby Gamma Knife and Dosimetric Control: Towards a Standardization

Authors: J. Constanzo, B. Paquette, G. Charest, L. Masson-Côté, M. Guillot

Abstract:

Targeted and whole-brain irradiation in humans can result in significant side effects causing decreased patient quality of life. To adequately investigate structural and functional alterations after stereotactic radiosurgery, preclinical studies are needed. The first step is to establish a robust standardized method of targeted irradiation on small regions of the rat brain. Eleven euthanized male Fischer rats were imaged in a stereotactic bed, by computed tomographic (CT), to estimate positioning variations regarding to the bregma skull reference point. Using a rat brain atlas and the stereotactic bregma coordinates assessed from CT images, various regions of the brain were delimited and a treatment plan was generated. A dose of 37 Gy at 30% isodose which corresponds to 100 Gy in 100% of the target volume (X = 98.1; Y = 109.1; Z = 100.0) was set by Leksell Gamma Plan using sectors number 4, 5, 7, and 8 of the Gamma Knife unit with the 4-mm diameter collimators. Effects of positioning accuracy of the rat brain on the dose deposition were simulated by Gamma Plan and validated with dosimetric measurements. Our results showed that 90% of the target volume received 110 ± 4.7 Gy and the maximum of deposited dose was 124 ± 0.6 Gy, which corresponds to an excellent relative standard deviation of 0.5%. This dose deposition calculated with the Gamma Plan was validated with the dosimetric films resulting in a dose-profile agreement within 2%, both in X- and Z-axis,. Our results demonstrate the feasibility to standardize the irradiation procedure of a small volume in the rat brain using a Gamma Knife.

Keywords: brain irradiation, dosimetry, gamma knife, small-animal irradiation, stereotactic radiosurgery (SRS)

Procedia PDF Downloads 405
1305 Structural Behaviour of Small-Scale Fibre-Filled Steel Tubular Planar Frames

Authors: Sadaf Karkoodi, Hassan Karampour

Abstract:

There is a growing interest in the construction industry towards hybrid systems. The hybrid systems use construction materials such as timber, steel, and concrete smartly, can be prefabricated, and are cost-effective and sustainable solutions to an industry targeting reduced carbon footprint. Moreover, in case of periodical shortage in timber resources, reusable and waste wood such as fibres can be used in the hybrid modules, which facilitates the circular economy. In this research, a hybrid frame is proposed and experimentally validated by introducing dried wood fibre products inside cold-formed steel square hollow sections without using any adhesives. As such, fibre-filled steel tubular (FFST) columns, beams, and 2D frames are manufactured and tested. The results show that the FFST columns have stiffness and strength 44% and 55% higher than cold-formed steel columns, respectively. The bearing strength of the FFST beams shows an increase of 39.5% compared to steel only. The flexural stiffness and strength of the FFST beams are 8.5% and 28% higher than the bare steel beams, respectively. The FFST frame depicted an 18.4% higher ultimate load capacity than the steel-only frame under a mid-point concentrated load. Moreover, the FFST beam-to-column bolted connection showed high ductile performance. The initial results and the proposed simple manufacturing process suggest that the proposed FFST concept can be upscaled and used in real structures.

Keywords: wood fibre, reusing wood, fibre-filled steel, hybrid construction

Procedia PDF Downloads 74
1304 Modelling Exchange-Rate Pass-Through: A Model of Oil Prices and Asymmetric Exchange Rate Fluctuations in Selected African Countries

Authors: Fajana Sola Isaac

Abstract:

In the last two decades, we have witnessed an increased interest in exchange rate pass-through (ERPT) in developing economies and emerging markets. This is perhaps due to the acknowledged significance of the pattern of exchange rate pass-through as a key instrument in monetary policy design, principally in retort to a shock in exchange rate in literature. This paper analyzed Exchange Rate Pass-Through by A Model of Oil Prices and Asymmetric Exchange Rate Fluctuations in Selected African Countries. The study adopted A Non-Linear Autoregressive Distributed Lag approach using yearly data on Algeria, Burundi, Nigeria and South Africa from 1986 to 2022. The paper found asymmetry in exchange rate pass-through in net oil-importing and net oil-exporting countries in the short run during the period under review. An ERPT exhibited a complete pass-through in the short run in the case of net oil-importing countries but an incomplete pass-through in the case of the net oil-exporting countries that were examined. An extended result revealed a significant impact of oil price shock on exchange rate pass-through to domestic price in the long run only for net oil importing countries. The Wald restriction test also confirms the evidence of asymmetric with the role of oil price acting as an accelerator to exchange rate pass-through to domestic price in the countries examined. The study found the outcome to be very useful for gaining expansive knowledge on the external shock impact on ERPT and could be of critical value for national monetary policy decisions on inflation targeting, especially for countries examined and other developing net oil importers and exporters.

Keywords: pass through, exchange rate, ARDL, monetary policy

Procedia PDF Downloads 72
1303 Identification of Potential Small Molecule Regulators of PERK Kinase

Authors: Ireneusz Majsterek, Dariusz Pytel, J. Alan Diehl

Abstract:

PKR-like ER kinase (PERK) is serine/threonie endoplasmic reticulum (ER) transmembrane kinase activated during ER-stress. PERK can activate signaling pathways known as unfolded protein response (UPR). Attenuation of translation is mediated by PERK via phosphorylation of eukaryotic initiation factor 2α (eIF2α), which is necessary for translation initiation. PERK activation also directly contributes to activation of Nrf2 which regulates expression of anti-oxidant enzymes. An increased phosphorylation of eIF2α has been reported in Alzheimer disease (AD) patient hippocampus, indicating that PERK is activated in this disease. Recent data have revealed activation of PERK signaling in non-Hodgkins lymphomas. Results also revealed that loss of PERK limits mammary tumor cell growth in vitro and in vivo. Consistent with these observations, activation of UPR in vitro increases levels of the amyloid precursor protein (APP), the peptide from which beta-amyloid plaques (AB) fragments are derived. Finally, proteolytic processing of APP, including the cleavages that produce AB, largely occurs in the ER, and localization coincident with PERK activity. Thus, we expect that PERK-dependent signaling is critical for progression of many types of diseases (human cancer, neurodegenerative disease and other). Therefore, modulation of PERK activity may be a useful therapeutic target in the treatment of different diseases that fail to respond to traditional chemotherapeutic strategies, including Alzheimer’s disease. Our goal will be to developed therapeutic modalities targeting PERK activity.

Keywords: PERK kinase, small molecule inhibitor, neurodegenerative disease, Alzheimer’s disease

Procedia PDF Downloads 477
1302 Investigating Spatial Disparities in Health Status and Access to Health-Related Interventions among Tribals in Jharkhand

Authors: Parul Suraia, Harshit Sosan Lakra

Abstract:

Indigenous communities represent some of the most marginalized populations globally, with India labeled as tribals, experiencing particularly pronounced marginalization and a concerning decline in their numbers. These communities often inhabit geographically challenging regions characterized by low population densities, posing significant challenges to providing essential infrastructure services. Jharkhand, a Schedule 5 state, is infamous for its low-level health status due to disparities in access to health care. The primary objective of this study is to investigate the spatial inequalities in healthcare accessibility among tribal populations within the state and pinpoint critical areas requiring immediate attention. Health indicators were selected based on the tribal perspective and association of Sustainable Goal 3 (Good Health and Wellbeing) with other SDGs. Focused group discussions in which tribal people and tribal experts were done in order to finalize the indicators. Employing Principal Component Analysis, two essential indices were constructed: the Tribal Health Index (THI) and the Tribal Health Intervention Index (THII). Index values were calculated based on the district-wise secondary data for Jharkhand. The bivariate spatial association technique, Moran’s I was used to assess the spatial pattern of the variables to determine if there is any clustering (positive spatial autocorrelation) or dispersion (negative spatial autocorrelation) of values across Jharkhand. The results helped in facilitating targeting policy interventions in deprived areas of Jharkhand.

Keywords: tribal health, health spatial disparities, health status, Jharkhand

Procedia PDF Downloads 89
1301 The Therapeutic Potential, Functions, and Use of Ibogaine

Authors: João Pedro Zanella, Michel J. O. Fagundes

Abstract:

Introduction: Drug use has been practised by humans universally for millennia, not excluding any population from these habits, however, the rampant drug use is a global concern due to the harm that affects the health of the world population. In this sense, it is observed the reduction of lasting and effective public policies for the resolution, increasing the demand for treatment services. With this comes ibogaine, an alkaloid derived from the root of an African bush (Tabernanthe Iboga), found mostly in Gabon and used widely by the native Bwiti population in rituals, and also other social groups, which demonstrates efficacy against chemical dependence, psychic and emotional disorders, opioid withdrawal was first confirmed by a study in rats done by Michailo Dzoljic and associates in 1988 and again in 1994. Methods: A brief description of the plant, its neurohumoral potential and the effects caused by ingested doses, in a simplified and objective way, will be discussed in the course of this abstract. Results: Ibogaine is not registered or passed by Anvisa, regarding safety and efficacy, and cannot be sold in Brazil. Its illegal trade reaches R$ 5 thousand for a session with the proceeds of the root, and its effect can last up to 72 hours, attributing Iboga's psychoactive effects to the alkaloid called ibogaine. The shrub where Ibogaine is located has pink and yellow flowers, and its fruit produced does not have psychoactive substances, but its root bark contains 6 to 7% indolic alkaloids. Besides extraction from the iboga plant, ibogaine hydrochloride can be semisynthesized from voacangine, another plant alkaloid that acts as a precursor. Its potential has the ability to perform multiple interactions with the neurotransmitter system, which are closely associated with addiction, including nicotinic, opioid and serotoninergic systems. Studies carried out by Edwards found that the doses administered of Iboga should be determined by a health professional when its purpose is to treat individuals for dependence on other drugs. Its use in small doses may cause an increase in sensibility, impaired vision and motor alterations; in moderate quantities, hallucinations, motor and neurological alterations and impaired vision; in high quantities it may cause hallucinations with personal events at a deeper level lasting up to 24 hours or more, followed by motor and visual alterations. Conclusion: The product extracted from the Iboga plant is of great importance in controlling addiction, reducing the need for the use of narcotics by patients, thus gaining a space of extreme importance in the treatment of users of psychoactive substances. It is remarkable the progress of the latest’s research about the usefulness of Ibogaine, and its benefits for certain treatments, even with the restriction of its sale in Brazil. Besides this, Ibogaine has an additional benefit of helping the patient to gain self-control over their destructive behaviours.

Keywords: alkaloids, dependence, Gabon, ibogaine

Procedia PDF Downloads 82
1300 Ethno-Medical Potentials of Tacazzea apiculata Oliv. (Periplocaceae)

Authors: Abubakar Ahmed, Zainab Mohammed, Hadiza D. Nuhu, Hamisu Ibrahim

Abstract:

Introduction: The plant Tacazzea apiculata Oliv (Periplocaceae) is widely distributed in tropical West Africa. It is claimed to have multiple uses in traditional medicine among which are its use to treat hemorrhoids, inflammations and cancers. Methods: Ethno-botanical survey through interview and using show-and-tell method of data collection were conducted among Hausa and Fulani tribes of northern Nigeria with the view to document useful information on the numerous claims by the local people on the plant. Results: The results revealed that the plant T. apiculata has relative popularity among the herbalist (38.2 %), nomads (14.8 %) and fishermen (16.0%). The most important uses of the plant in traditional medicine are inflammation (Fedelity level: 25.7 %) and Haemorrhoids (Fedelity level: 17.1 %) Conclusion: These results suggest the relevance of T. apiculata in traditional medicine and as a good candidate for drug Development.

Keywords: ethno-botany, periplocaceae, Tacazzea apiculata, traditional medicine

Procedia PDF Downloads 509
1299 Blood Clot Emulsification via Ultrasonic Thrombolysis Device

Authors: Sun Tao, Lou Liang, Tan Xing Haw Marvin, Gu Yuandong Alex

Abstract:

Patients with blood clots in their brains can experience problems with their vision or speech, seizures and general weakness. To treat blood clots, clinicians presently have two options. The first involves drug therapy to thin the blood and thus reduce the clot. The second choice is to invasively remove the clot using a plastic tube called a catheter. Both approaches carry a high risk of bleeding, and invasive procedures, such as catheter intervention, can also damage the blood vessel wall and cause infection. Ultrasonic treatment as a potential alternative therapy to break down clots is attracting growing interests due to the reduced adverse effects. To demonstrate the concept, in this investigation a microfabricated ultrasonic device was electrically packaged with printed circuit board to treat healthy human blood. The red blood cells could be broken down after 3-hour ultrasonic treatment.

Keywords: microfabrication, blood clot, ultrasonic thrombolysis device, ultrasonic device

Procedia PDF Downloads 445
1298 Analysis of Nitrogenase Fe Protein Activity in Transplastomic Tobacco

Authors: Jose A. Aznar-Moreno, Xi Jiang, Stefan Burén, Luis M. Rubio

Abstract:

Integration of prokaryotic nitrogen fixation (nif) genes into the plastid genome for expression of functional nitrogenase components could render plants capable of assimilating atmospheric N2 making their crops less dependent of nitrogen fertilizers. The nitrogenase Fe protein component (NifH) has been used as proxy for expression and targeting of Nif proteins within plant and yeast cells. Here we use tobacco plants with the Azotobacter vinelandii nifH and nifM genes integrated into the plastid genome. NifH and its maturase NifM were constitutively produced in leaves, but not roots, during light and dark periods. Nif protein expression in transplastomic plants was stable throughout development. Chloroplast NifH was soluble, but it only showed in vitro activity when isolated from leaves collected at the end of the dark period. Exposing the plant extracts to elevated temperatures precipitated NifM and apo-NifH protein devoid of [Fe4S4] clusters, dramatically increasing the specific activity of remaining NifH protein. Our data indicate that the chloroplast endogenous [Fe-S] cluster biosynthesis was insufficient for complete NifH maturation, albeit a negative effect on NifH maturation due to excess NifM in the chloroplast cannot be excluded. NifH and NifM constitutive expression in transplastomic plants did not affect any of the following traits: seed size, germination time, germination ratio, seedling growth, emergence of the cotyledon and first leaves, chlorophyll content and plant height throughout development.

Keywords: NifH, chloroplast, nitrogen fixation, crop improvement, transplastomic plants, fertilizer, biotechnology

Procedia PDF Downloads 155
1297 Productive Safety Net Program and Rural Livelihood in Ethiopia

Authors: Desta Brhanu Gebrehiwot

Abstract:

The purpose of this review was to analyze the overall or combined effect of scholarly studies conducted on the impacts of Food for work (FFW) and Productive Safety Net Program (PSNP) on farm households’ livelihood (agricultural investment on the adoption of fertilizer, food security, livestock holding, nutrition and its’ disincentive effect) in Ethiopia. In addition, to make a critical assessment of the internal and external validity of the existing studies, the review also indicates the possibility to redesign the program. The method of selecting eligible studies for review was PICOS (Participants, Intervention, Comparison, Outcomes, and Settings) framework. The method of analysis was the fixed effects model under Meta-Analysis. The findings of this systematic review confirm the overall or combined positive significant impact of PSNP on fertilizer adoption (combined point estimate=0.015, standard error=0.005, variance=0.000, lower limit 0.004 up to the upper limit=0.026, z-value=2.726, and p-value=0.006). And the program had a significant positive impact on the child nutrition of rural households and had no significant disincentive effect. However, the program had no significant impact on livestock holdings. Thus, PSNP is important for households whose livelihood depends on rain-fed agriculture and are exposed to rainfall shocks. Thus, better to integrate the program into the national agricultural policy. In addition, most of the studies suggested that PSNP needs more attention to the design and targeting issued in order to be effective and efficient in social protection.

Keywords: meta-analysis, fixed effect model, PSNP, rural-livelihood, Ethiopia

Procedia PDF Downloads 66
1296 Towards the Effectiveness/ Performance of Spatial Communication within the Composite Interior Spaces: Wayfinding System in the Saudi National Museum as a Case Study

Authors: Afnan T. Bagasi, Donia M. Bettaieb, Abeer Alsobahi

Abstract:

The wayfinding system is related to the course of the museum journey for visitors directly and indirectly. The design aspects of this system play an important role, making it an effective and communication system within the museum space. However, translating the concepts that pertain to its design, such as Intelligibility that is based on integration and connectivity in museum space design, needs more customization in the form of specific design considerations with reference to the most important approaches. Those approaches link the organizational and practical aspects to the semiotic and semantic aspects related to the space syntax by targeting the visual and perceived consistency of visitors. In this context, the study aims to identify how to apply the concept of intelligibility and clarity by employing integration and connectivity to design a wayfinding system in museums as a kind of composite interior space. Using the available plans and images to extrapolate the design considerations used to design the wayfinding system in the Saudi National Museum as a case study, a descriptive-analytical method was used to understand the basic organizational and morphological principles of the museum space through four main aspects in space design: morphological, semantic, semiotic, and pragmatic. The study's findings will assist designers, professionals, and researchers in the field of museum design in understanding the significance of the wayfinding system by delving into it through museum spaces by highlighting the essential aspects using a clear analytical method.

Keywords: wayfinding system, museum journey, intelligibility, integration, connectivity

Procedia PDF Downloads 168
1295 Influence of Natural Gum on Curcumin Supersaturationin Gastrointestinal Fluids

Authors: Patcharawalai Jaisamut, Kamonthip Wiwattanawongsa, Ruedeekorn Wiwattanapatapee

Abstract:

Supersaturation of drugs in the gastrointestinal tract is one approach to increase the absorption of poorly water-soluble drugs. The stabilization of a supersaturated state was achieved by adding precipitation inhibitors that may act through a variety of mechanisms.In this study, the effect of the natural gums, acacia, gelatin, pectin and tragacanth on curcumin supersaturation in simulated gastric fluid (SGF) (pH 1.2), fasted state simulated gastric fluid (FaSSGF) (pH 1.6), and simulated intestinal fluid (SIF) (pH 6.8)was investigated. The results indicated that all natural gums significantly increased the curcum insolubility (about 1.2-6-fold)when compared to the absence of gum, and assisted in maintaining the supersaturated drug solution. Among the tested gums, pectin at 3% w/w was the best precipitation inhibitor with a significant increase in the degree of supersaturation about 3-fold in SGF, 2.4-fold in FaSSGF and 2-fold in SIF.

Keywords: curcumin, solubility, supersaturation, precipitation inhibitor

Procedia PDF Downloads 345
1294 Targeting NLRP3 Inflammasome Activation: A New Mechanism Underlying the Protective Effects of Nafamostat Against Acute Pancreatitis

Authors: Jiandong Ren, Lijun Zhao, Peng Chen

Abstract:

Nafamostat (NA), a synthetic broad-spectrum serine protease inhibitor, has been routinely employed for the treatment of acute pancreatitis (AP) and other inflammatory-associated diseases in some East Asia countries. Although the potent inhibitory activity against inflammation-related proteases such as thrombin, trypsin, kallikrein, plasmin, coagulation factors and complement factors is generally considered to be responsible for the anti-inflammatory effects of NA, precise target and molecular mechanism underlying the anti-inflammatory activity in the treatment of AP remain largely unknown yet. As an intracellular inflammatory signaling platform, the NOD-like receptor protein 3 (NLRP3) inflammasome is recently identified to be involved in the development of AP. In present study, we have revealed that NA alleviated pancreatic injury in a caerulein-induced AP model by inhibiting the NLRP3 inflammasome activation in pancreas. Mechanistically, NA interacted with HDAC6, a cytoplasmic deacetylase implicated in the NLRP3 inflammasome pathway, and efficiently abrogated the function of HDAC6. This property enabled NA to influence HDAC6 dependent NF-κB transcriptional activity and thus block NF-κB-driven transcriptional priming of NLRP3 inflammasome. Moreover, NA exerted the potential to interfere HDAC6-mediated intracellular transport of NLRP3, thereby leading to the failure of NLRP3 inflammasome activation. Our current work has provided valuable insight into the molecular mechanism underlying the immunomodulatory effect of NA in treatment of AP, highlighting its promising application in prevention of NLRP3 inflammasome-associated inflammatory pathological damage.

Keywords: acute pancreatitis, HDAC6, nafamostat, NLRP3 inflammasome

Procedia PDF Downloads 65
1293 A Unified Model for Orotidine Monophosphate Synthesis: Target for Inhibition of Growth of Mycobacterium tuberculosis

Authors: N. Naga Subrahmanyeswara Rao, Parag Arvind Deshpande

Abstract:

Understanding nucleotide synthesis reaction of any organism is beneficial to know the growth of it as in Mycobacterium tuberculosis to design anti TB drug. One of the reactions of de novo pathway which takes place in all organisms was considered. The reaction takes places between phosphoribosyl pyrophosphate and orotate catalyzed by orotate phosphoribosyl transferase and divalent metal ion gives orotdine monophosphate, a nucleotide. All the reaction steps of three experimentally proposed mechanisms for this reaction were considered to develop kinetic rate expression. The model was validated using the data for four organisms. This model could successfully describe the kinetics for the reported data. The developed model can serve as a reliable model to describe the kinetics in new organisms without the need of mechanistic determination. So an organism-independent model was developed.

Keywords: mechanism, nucleotide, organism, tuberculosis

Procedia PDF Downloads 329
1292 Standardization of the Roots of Gnidia stenophylla Gilg: A Potential Medicinal Plant of South Eastern Ethiopia Traditionally Used as an Antimalarial

Authors: Mebruka Mohammed, Daniel Bisrat, Asfaw Debella, Tarekegn Birhanu

Abstract:

Lack of quality control standards for medicinal plants and their preparations is considered major barrier to their integration in to effective primary health care in Ethiopia. Poor quality herbal preparations led to countless adverse reactions extending to death. Denial of penetration for the Ethiopian medicinal plants in to the world’s booming herbal market is also another significant loss resulting from absence of herbal quality control system. Thus, in the present study, Gnidia stenophylla Gilg (popular antimalarial plant of south eastern Ethiopia), is standardized and a full monograph is produced that can serve as a guideline in quality control of the crude drug. Morphologically, the roots are found to be cylindrical and tapering towards the end. It has a hard, corky and friable touch with saddle brown color externally and it is relatively smooth and pale brown internally. It has got characteristic pungent odor and very bitter taste. Microscopically it has showed lignified xylem vessels, wider medullary rays with some calcium oxalate crystals, reddish brown secondary metabolite contents and slender shaped long fibres. Physicochemical standards quantified and resulted: foreign matter (5.25%), moisture content (6.69%), total ash (40.80%), acid insoluble ash (8.00%), water soluble ash (2.30%), alcohol soluble extractive (15.27%), water soluble extractive (10.98%), foaming index (100.01 ml/g), swelling index (7.60 ml/g). Phytochemically: Phenols, flavonoids, steroids, tannins and saponins were detected in the root extract; TLC and HPLC fingerprints were produced and an analytical marker was also tentatively characterized as 3-(3,4-dihydro-3,5-dihydroxy-2-(4-hydroxy-5-methylhex-1-en-2-yl)-7-methoxy-4-oxo-2H-chromen-8-yl)-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one. Residue wise pesticides (i.e. DDT, DDE, g-BHC) and radiochemical levels fall below the WHO limit while Heavy metals (i.e. Co, Ni, Cr, Pb, and Cu), total aerobic count and fungal load lie way above the WHO limit. In conclusion, the result can be taken as signal that employing non standardized medicinal plants could cause many health risks of the Ethiopian people and Africans’ at large (as 80% of inhabitants in the continent depends on it for primary health care). Therefore, following a more universal approach to herbal quality by adopting the WHO guidelines and developing monographs using the various quality parameters is inevitable to minimize quality breach and promote effective herbal drug usage.

Keywords: Gnidia stenophylla Gilg, standardization/monograph, pharmacognostic, residue/impurity, quality

Procedia PDF Downloads 284
1291 Synergistic Effect between Titanium Oxide and Silver Nanoparticles in Polymeric Binary Systems

Authors: Raquel C. A. G. Mota, Livia R. Menezes, Emerson O. da Silva

Abstract:

Both silver nanoparticles and titanium dioxide have been extensively used in tissue engineering since they’ve been approved by the Food and Drug Administration (FDA), and present a bactericide effect when added to a polymeric matrix. In this work, the focus is on fabricating binary systems with both nanoparticles so that the synergistic effect can be investigated. The systems were tested by Nuclear Magnetic Resonance (NMR), Thermogravimetric Analysis (TGA), Fourier-Transformed Infrared (FTIR), and Differential Scanning Calorimetry (DSC), and X-ray Diffraction (XRD), and had both their bioactivity and bactericide effect tested. The binary systems presented different properties than the individual systems, enhancing both the thermal and biological properties as was to be expected. The crystallinity was also affected, as indicated by the finding of the DSC and XDR techniques, and the NMR showed a good dispersion of both nanoparticles in the polymer matrix. These findings indicate the potential of combining TiO₂ and silver nanoparticles in biomedicine.

Keywords: metallic nanoparticles, nanotechnology, polymer nanocomposites, polymer science

Procedia PDF Downloads 129
1290 Separation of Fexofenadine Enantiomers Using Beta Cyclodextrin as Chiral Counter Ion in Mobile Phase

Authors: R. Fegas, S. Zerkout, S. Taberkokt, M. Righezza

Abstract:

The present work demonstrate the potential of Betacyclodextrine (BCD) for the chiral analysis of a drug .Various separation mechanisms were applied and several parameters affecting the separation were studied, including the type and concentration of chiral selector, and pH of buffer. A simple and sensitive high-performance liquid chromatography (HPLC) method was developed as an assay for fexofenadine enantiomers in pharmaceutical preparation. Fexofenadine enantiomers were separated using a mobile phase of 0.25mM NaH2PO4–acetonitrile (65:35, v/v) – Betacyclodextrine on achiral phenyl-urea column at a flow rate of 1ml/min and measurement at 220nm. The chiral mechanism of separation was mainly based on specific interaction between the solute and the stationary phase. The retention was directly controlled by mobile phase composition but not the selectivity which results of the two mechanisms, electrostatic interactions and partition mechanism.

Keywords: fexofenadine enantiomer, HPLC, achiral phenyl-urea column

Procedia PDF Downloads 456
1289 Gamma-Hydroxybutyrate (GHB): A Review for the Prehospital Clinician

Authors: Theo Welch

Abstract:

Background: Gamma-hydroxybutyrate (GHB) is a depressant of the central nervous system with euphoric effects. It is being increasingly used recreationally in the United Kingdom (UK) despite associated morbidity and mortality. Due to the lack of evidence, healthcare professionals remain unsure as to the optimum management of GHB acute toxicity. Methods: A literature review was undertaken of its pharmacology and the emergency management of its acute toxicity.Findings: GHB is inexpensive and readily available over the Internet. Treatment of GHB acute toxicity is supportive. Clinicians should pay particular attention to the airway as emesis is common. Intubation is required in a minority of cases. Polydrug use is common and worsens prognosis. Conclusion: An inexpensive and readily available drug, GHB acute toxicity can be difficult to identify and treat. GHB acute toxicity is generally treated conservatively. Further research is needed to ascertain the indications, benefits, and risks of intubating patients with GHB acute toxicity. instructions give you guidelines for preparing papers for the conference.

Keywords: GHB, gamma-hydroxybutyrate, prehospital, emergency, toxicity, management

Procedia PDF Downloads 193
1288 Rapid Mitochondrial Reactive Oxygen Species Production Precedes NF-κB Activation and Pro-inflammatory Responses in Macrophages

Authors: Parinaz Tavakoli Zaniani, Dimitrios Balomenos

Abstract:

Mitochondrial reactive oxygen species (mROS) play a crucial role in macrophage pro-inflammatory activation, although a detailed understanding of the mechanism and kinetics by which mROS drive signaling molecules is still lacking. In general, it is thought that NF-κB activation drives mROS and general ROS production. Here, We performed a detailed kinetic analysis of mROS production during macrophage activation. We found early mROS generation after LPS (lipopolysaccharide) stimulation. Remarkably as early as 5 minutes, mROS signaling promoted initial NF-κB, MAPK activation and pro-inflammatory cytokine production, as established through inhibition or quenching of mROS. On the contrary, NF-κB inhibition had no effect on mROS production. Our findings point to a mechanism by which mROS increase TRAF-6 ubiquitination and, thus NF-κB activity. mROS inhibition reduced LPS-induced lethality in an in vivo septic shock model by controlling pro-inflammatory cytokine production. Overall, our research provides novel insights into the role of mROS as a primary messenger in the pathway of macrophage and as a regulator of inflammatory responses. We found that early mROS production promotes initial NF-κB, and MAPK activation by regulating TRAF-6 ubiquitination and that mROS inhibition can reduce LPS-induced inflammatory cytokines and lethality in a septic shock model. These findings might lead to novel immunotherapeutic strategies targeting early mROS production and control of extreme inflammation in the context of sepsis and other inflammatory diseases.

Keywords: mitochondria, reactive oxygen species, nuclear factor κB, lipopolysaccharide, macrophages

Procedia PDF Downloads 66
1287 Farmers’ Access to Agricultural Extension Services Delivery Systems: Evidence from a Field Study in India

Authors: Ankit Nagar, Dinesh Kumar Nauriyal, Sukhpal Singh

Abstract:

This paper examines the key determinants of farmers’ access to agricultural extension services, sources of agricultural extension services preferred and accessed by the farmers. An ordered logistic regression model was used to analyse the data of the 360 sample households based on a primary survey conducted in western Uttar Pradesh, India. The study finds that farmers' decision to engage in the agricultural extension programme is significantly influenced by factors such as education level, gender, farming experience, social group, group membership, farm size, credit access, awareness about the extension scheme, farmers' perception, and distance from extension sources. The most intriguing finding of this study is that the progressive farmers, which have long been regarded as a major source of knowledge diffusion, are the most distrusted sources of information as they are suspected of withholding vital information from potential beneficiaries. The positive relationship between farm size and ‘Access’ underlines that the extension services should revisit their strategies for targeting more marginal and small farmers constituting over 85 percent of the agricultural households by incorporating their priorities in their outreach programs. The study suggests that marginal and small farmers' productive potential could still be greatly augmented by the appropriate technology, advisory services, guidance, and improved market access. Also, the perception of poor quality of the public extension services can be corrected by initiatives aimed at building up extension workers' capacity.

Keywords: agriculture, access, extension services, ordered logistic regression

Procedia PDF Downloads 210
1286 Spatial Rank-Based High-Dimensional Monitoring through Random Projection

Authors: Chen Zhang, Nan Chen

Abstract:

High-dimensional process monitoring becomes increasingly important in many application domains, where usually the process distribution is unknown and much more complicated than the normal distribution, and the between-stream correlation can not be neglected. However, since the process dimension is generally much bigger than the reference sample size, most traditional nonparametric multivariate control charts fail in high-dimensional cases due to the curse of dimensionality. Furthermore, when the process goes out of control, the influenced variables are quite sparse compared with the whole dimension, which increases the detection difficulty. Targeting at these issues, this paper proposes a new nonparametric monitoring scheme for high-dimensional processes. This scheme first projects the high-dimensional process into several subprocesses using random projections for dimension reduction. Then, for every subprocess with the dimension much smaller than the reference sample size, a local nonparametric control chart is constructed based on the spatial rank test to detect changes in this subprocess. Finally, the results of all the local charts are fused together for decision. Furthermore, after an out-of-control (OC) alarm is triggered, a diagnostic framework is proposed. using the square-root LASSO. Numerical studies demonstrate that the chart has satisfactory detection power for sparse OC changes and robust performance for non-normally distributed data, The diagnostic framework is also effective to identify truly changed variables. Finally, a real-data example is presented to demonstrate the application of the proposed method.

Keywords: random projection, high-dimensional process control, spatial rank, sequential change detection

Procedia PDF Downloads 295
1285 FC and ZFC Studies of Nickel Nano Ferrites and Ni Doped Lithium Nano Ferrites by Citrate-Gel Auto Combustion Method

Authors: D. Ravinder

Abstract:

Nickel ferrites and Ni doped Lithium nano ferrites [Li0.5Fe0.5]1-xNixFe2O4 with x= 0.8 and 1.0 synthesized by citrate-gel auto combustion method. The broad peaks in the X-ray diffraction pattern (XRD) indicate a crystalline behavior of the prepared samples. Low temperature magnetization studies i,e Field Cooled (FC) and Zero Field Cooled (ZFC) magnetic studies of the investigated samples are measured by using vibrating sample magnetometer (VSM). The magnetization of the prepared samples as a function of an applied magnetic field 10 T was measured at two different temperatures 5 K and 310 K. Field Cooled (FC) and Zero Field Cooled (ZFC) magnetization measurements under an applied field of 100 Oe and 1000 Oe in the temperature range of 5–375 K were carried out.

Keywords: ferro-spinels, field cooled (FC), Zero Field Cooled (ZFC) and blocking temperature, superpara magnetism, drug delivery applications

Procedia PDF Downloads 553
1284 Mapping Protein Selectivity Landscapes

Authors: Niv Papo

Abstract:

Characterizing the binding selectivity landscape of interacting proteins is crucial both for elucidating the underlying mechanisms of their interaction and for developing selective inhibitors. However, current mapping methods are laborious and cannot provide a sufficiently comprehensive description of the landscape. Here, we introduce a distinct and efficient strategy for comprehensively mapping the binding landscape of proteins using a combination of experimental multi-target selective library screening and in silico next-generation sequencing analysis. We map the binding landscape of a non-selective trypsin inhibitor, the amyloid protein precursor inhibitor (APPI), to each of four human serine proteases (kallikrein-6, mesotrypsin, and anionic and cationic trypsins). We then use this map to dissect and improve the affinity and selectivity of APPI variants toward each of the four proteases. Our strategy can be used as a platform for the development of a new generation of target-selective probes and therapeutic agents based on selective protein–protein interactions.

Keywords: drug design, directed evolution, protein engineering, protease inhibition.

Procedia PDF Downloads 13
1283 Mitigating the Aggregation of Human Islet Amyloid Polypeptide with Nanomaterials

Authors: Ava Faridi, Pouya Faridi, Aleksandr Kakinen, Ibrahim Javed, Thomas P. Davis, Pu Chun Ke

Abstract:

Human islet amyloid polypeptide (IAPP) is a hormone associated with glycemic control and type 2 diabetes. Biophysically, the chirality of IAPP fibrils has been little explored with respect to the aggregation and toxicity of the peptide. Biochemically, it remains unclear as for how protein expression in pancreatic beta cells may be altered by cell exposure to the peptide, and how such changes may be mitigated by nanoparticle inhibitors for IAPP aggregation. In this study, we first demonstrated the elimination of the IAPP nucleation phase and shortening of its elongation phase by silica nanoribbons. This accelerated IAPP fibrillization translated to reduced toxicity, especially for the right-handed silica nanoribbons, as revealed by cell viability, helium ion microscopy, as well as zebrafish embryo survival, developmental and behavioral assays. We then examined the proteomes of βTC6 pancreatic beta cells exposed to the three main aggregation states of monomeric, oligomeric and amyloid fibrillar IAPP, and compared that with cellular protein expression modulated by graphene quantum dots (GQDs). A total of 29 proteins were significantly regulated by different forms of IAPP, and the majority of these proteins were nucleotide-binding proteins. A regulatory capacity of GQDs against aberrant protein expression was confirmed. These studies have demonstrated the great potential of employing nanomaterials targeting the mesoscopic enantioselectivity and protein expression dysregulation in pancreatic beta cells.

Keywords: graphene quantum dots, IAPP, silica nanoribbons, protein expression, toxicity

Procedia PDF Downloads 138
1282 Hepatoprotective Effect of Mycophenolate Mofetil against Tacrolimus Exposure in Rat

Authors: Ferjani Hanen, El Arem Amira, Boussema Ayed Imen, Bacha Hassen

Abstract:

Tacrolimus (TAC), a calcineurin inhibitor, is clinically used as an immunosuppressive agent in the transplant recipient, but its use associated-hepatotoxicity. Mycophenolate mofetil (MMF), an anti-metabolite, is a potent immunosuppressive drug. MMF is not hepatotoxic and is the most common adjunctive immunosuppressant for TAC. The effects of TAC and MMF combination in the liver is still not well understood. This work aimed to investigate their combined effect against in liver in rats Wistar after 24 h. The oral median lethal doses (LD50) of TAC and MMF alone were evaluated in rats are 240 mg/kg and 500 mg/kg respectively. Oral administration of the MMF at 50 mg/kg to male Wistar intoxicated with TAC at 60 mg/kg, demonstrated a significant protective effect by lowering the levels of hepatic markers enzymes (AST, ALT) in the serum rat. MMF attenuated oxidative stress by restoring the activities of SOD, CAT and by reducing the malondialdehyde (MDA) and protein carbonyl levels liver. This study provided evidence that MMF protects rat liver from TAC-induced injury and suggests a most combination use for organ transplantation.

Keywords: tacrolimus, mycophenolate mofetil, combination, liver, rat

Procedia PDF Downloads 331
1281 In vitro and invivo Antioxidant Studies of Grewia crenata Leaves Extract in Albino Rats

Authors: A. N.Ukwuani, A. K. Abdulfatah

Abstract:

G. crenata is used locally for the treatment of fractured bones, wound healing and inflammatory conditions. In vitro and in vivo antioxidant activity of hydromethanolic extracts of the leaves of G. crenata were assessed. The phytochemical analysis shows the presence of phenols, flavonoids, saponins, cardiac glycosides and tannins. An in vitro quantitative analysis of phenols, flavonoids and tannins respectively were (164±1.20, 199±0.88 and 88.67±0.88 mg/100g FW). In vivo studies of hydromethanolic extract demonstrated a dose dependent increase in hepatic superoxide dismutase (1.14±0.14, 2.13±0.11, 2.55±0.11 U/mg Protein) with improvement in hepatic glutathione (6.98±0.42, 8.91±0.37, 11.07±0.46 µM/mg Protein) and Catalase (4.47±0.05, 6.24±0.02, 7.17±0.04 U/mg Protein) and Total protein (6.18±0.08, 6.69±0.18, 7.27±0.16 mg/ml) respectively at 100-300mg/kg body weight Grewia crenata leaves when compared to the control and standard drug. It can be concluded from the present findings of that G. crenata leaves possess antioxidant potential.

Keywords: Grewia crenata, antioxidant, hydromethanolic extract, in vivo, in vitro

Procedia PDF Downloads 543