154 resultados para Atypische Antispsychitika, Therapeutisches Drug Monitoring
Resumo:
Electronic monitoring of perimeters plays vital roles in homeland security, management of traffic and of humanwildlife conflict. This paper reports the design and development of an optical beam-interruption-based ranging and profiling sensor for monitoring perimeters. The developed sensor system can determine the distance of the object from the sensing units and its temporal height profile as the object crosses the system. Together, these quantities can also be used to classify the object and to determine its speed. The sensor is designed, fabricated, and evaluated. The design enables compact construction, high sensitivity, and low measurement crosstalk. The evaluation demonstrates accuracy better than 98.5% in the determination of height and over 94% in determination of the distance of an object from the sensing units. Finally, a strategy is proposed to classify the objects based on the obtained height profiles. The strategy is demonstrated to correctly classify the objects despite differences in their speed and the location at which they cross the system.
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Hydrochlorothiazide (HCT) is a diuretic and a BCS class IV drug with low solubility and low permeability, exhibiting poor oral absorption. The present study attempts to improve the physicochemical properties of the drug using a crystal engineering approach with cocrystals. Such multicomponent crystals of HCT with nicotinic acid (NIC), nicotinamide (NCT), 4-aminobenzoic acid (PABA), succinamide (SAM), and resorcinol (RES) were prepared using liquid-assisted grinding, and their solubilities in pH 7.4 buffer were evaluated. Diffusion and membrane permeability were studied using a Franz diffusion cell. Except for the SAM and NIC cocrystals, all other binary systems exhibited improved solubility. All of the cocrystals showed improved diffusion/membrane permeability compared to that of HCT with the exception of the SAM cocrystal. When the solubility was high, as in the case of PABA, NCT, and RES cocrystals, the flux/permeability dropped slightly. This is in agreement with the expected interplay between solubility and permeability. Improved solubility/permeability is attributed to new drug-coformer interactions. Cocrystals of SAM, however, showed poor solubility and flux This cocrystal contains a primary sulfonamide dimer synthon similar to that of HCT polymorphs, which may be a reason for its unusual behavior. Hirshfeld surface analysis was carried out in all cases to determine whether a correlation exists between cocrystal permeability and drug-coformer interactions.
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Multidrug resistance is a major therapeutic challenge faced in the conventional chemotherapy. Nanocarriers are beneficial in the transport of chemotherapeutics by their ability to bypass the P-gp efflux in cancers. Most of the P-gp inhibitors under phase II clinical trial are facing failures and hence there is a need to develop a suitable carrier to address P-gp efflux in cancer therapy. Herein, we prepared novel protamine and carboxymethyl cellulose polyelectrolyte multi-layered nanocapsules modified with Fe3O4 nanoparticles for the delivery of doxorubicin against highly drug resistant HeLa cells. The experimental results revealed that improved cellular uptake, enhanced drug intensity profile with greater percentage of apoptotic cells was attained when doxorubicin loaded magnetic nanocapsules were used in the presence of external magnetic field. Hence, we conclude that this magnetic field assisted nanocapsule system can be used for delivery of chemotherapeutics for potential therapeutic efficacy at minimal dose in multidrug resistant cancers. From the Clinical Editor: Many cancer drugs fail when cancer cells become drug resistant. Indeed, multidrug resistance (MDR) is a major therapeutic challenge. One way that tumor cells attain MDR is by over expression of molecular pumps comprising of P-glycoprotein (P-gp) and multidrug resistant proteins (MRP), which can expel chemotherapeutic drugs out of the cells. In this study, the authors prepared novel protamine and carboxymethyl cellulose polyelectrolyte multi-layered nanocapsules modified with Fe3O4 nanoparticles for the delivery of doxorubicin. The results show that there was better drug delivery and efficacy even against MDR tumor cells. (C) 2015 Elsevier Inc. All rights reserved.
Resumo:
Structural Health Monitoring (SHM) systems require integration of non-destructive technologies into structural design and operational processes. Modeling and simulation of complex NDE inspection processes are important aspects in the development and deployment of SHM technologies. Ray tracing techniques are vital simulation tools to visualize the wave path inside a material. These techniques also help in optimizing the location of transducers and their orientation with respect to the zone of interrogation. It helps in increasing the chances of detection and identification of a flaw in that zone. While current state-of-the-art techniques such as ray tracing based on geometric principle help in such visualization, other information such as signal losses due to spherical or cylindrical shape of wave front are rarely taken into consideration. The problem becomes a little more complicated in the case of dispersive guided wave propagation and near-field defect scattering. We review the existing models and tools to perform ultrasonic NDE simulation in structural components. As an initial step, we develop a ray-tracing approach, where phase and spectral information are preserved. This enables one to study wave scattering beyond simple time of flight calculation of rays. Challenges in terms of theory and modelling of defects of various kinds are discussed. Various additional considerations such as signal decay and physics of scattering are reviewed and challenges involved in realistic computational implementation are discussed. Potential application of this approach to SHM system design is highlighted and by applying this to complex structural components such as airframe structures, SHM is demonstrated to provide additional value in terms of lighter weight and/or longevity enhancement resulting from an extension of the damage tolerance design principle not compromising safety and reliability.
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Microneedle technology is one of the attractive methods in transdermal drug delivery. However, the clinical applications of this method are limited owing to: complexity in the preparation of multiple coating solutions, drug leakage while inserting the microneedles into the skin and the outer walls of the solid microneedle can hold limited quantity of drug. Here, the authors present the fabrication of an array of rectangular cup shaped silicon microneedles, which provide for reduced drug leakage resulting in improvement of efficiency of drug delivery and possibility of introducing multiple drugs. The fabricated solid microneedles with rectangular cup shaped tip have a total height of 200 mu m. These cup shaped tips have dimensions: 60 x 60 mu m (length x breadth) with a depth of 60 mu m. The cups are filled with drug using a novel in-house built drop coating system. Successful drug dissolution was observed when the coated microneedle was used on mice. Also, using the above method, it is possible to fill the cups selectively with different drugs, which enables simultaneous multiple drug delivery. (C) 2015 American Vacuum Society.
Resumo:
Communication and environmental monitoring play a major role in underground mining both from production and safety point of view. However, underground mining communication as well as monitoring devices encounter several challenges because of the nature of underground features and characteristics. Lack of real time information from underground workings may hamper production and create serious safety risks. Proper communication and monitoring devices are inevitable requirements for better production and improved safety. Communication and environmental monitoring devices are basic element of underground mine infrastructure. This paper describes the performance of communication and monitoring devices being used in underground mines. An attempt has been made to assess the safety risks by these devices which may dictate future research directions.
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Objectives: The ability to target conventional drugs efficiently inside cells to kill intraphagosomal bacteria has been a major hurdle in treatment of infective diseases. We aimed to develop an efficient drug delivery system for combating infection caused by Salmonella, a well-known intracellular and intraphagosomal pathogen. Chitosan dextran sulphate (CD) nanocapsules were assessed for their efficiency in delivering drugs against Salmonella. Methods: The CD nanocapsules were prepared using the layer-by-layer method and loaded with ciprofloxacin or ceftriaxone. Antibiotic-loaded nanocapsules were analysed in vitro for their ability to enter epithelial and macrophage cells to kill Salmonella. In vivo pharmacokinetics and organ distribution studies were performed to check the efficiency of the delivery system. The in vivo antibacterial activity of free antibiotic and antibiotic loaded into nanocapsules was tested in a murine salmonellosis model. Results: In vitro and in vivo experiments showed that this delivery system can be used effectively to clear Salmonella infection, CD nanocapsules were successfully employed for efficient targeting and killing of the intracellular pathogen at a dosage significantly lower than that of the free antibiotic. The increased retention time of ciprofloxacin in the blood and organs when it was delivered by CD nanocapsules compared with the conventional routes of administration may be the reason underlying the requirement for a reduced dosage and frequency of antibiotic administration. Conclusions: CD nanocapsules can be used as an efficient drug delivery system to treat intraphagosomal pathogens, especially Salmonella infection, This delivery system might be used effectively for other vacuolar pathogens including Mycobacteria, Brucella and Legionella.
Resumo:
Non-invasive, real-time dynamic monitoring of pressure inside a column with the aid of Fiber Bragg Grating (FBG) sensor is presented in the present work. A bare FBG sensor is adhered on the circumference of a pressure column normal to its axis, which has the ability to acquire the hoop strain induced by the pressure variation inside the column. Pressure induced hoop strain response obtained using FBG sensor is validated against the pressure measurements obtained from conventional pressure gauge. Further, a protrusion setup on the outer surface of the column has been proposed over which a secondary FBG sensor is bonded normal to its axis, in order to increase the gauge length of this FBG sensor. This is carried out in order to validate the variation in sensitivity of the protrusion bonded FBG sensor compared to the bare FBG sensor bonded over the surface. A comparative study is done between the two FBG sensors and a conventional pressure gauge in order to establish the capacity of FBG sensor obtained hoop strain response for pressure monitoring inside the column.
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The growing number of applications and processing units in modern Multiprocessor Systems-on-Chips (MPSoCs) come along with reduced time to market. Different IP cores can come from different vendors, and their trust levels are also different, but typically they use Network-on-Chip (NoC) as their communication infrastructure. An MPSoC can have multiple Trusted Execution Environments (TEEs). Apart from performance, power, and area research in the field of MPSoC, robust and secure system design is also gaining importance in the research community. To build a secure system, the designer must know beforehand all kinds of attack possibilities for the respective system (MPSoC). In this paper we survey the possible attack scenarios on present-day MPSoCs and investigate a new attack scenario, i.e., router attack targeted toward NoC architecture. We show the validity of this attack by analyzing different present-day NoC architectures and show that they are all vulnerable to this type of attack. By launching a router attack, an attacker can control the whole chip very easily, which makes it a very serious issue. Both routing tables and routing logic-based routers are vulnerable to such attacks. In this paper, we address attacks on routing tables. We propose different monitoring-based countermeasures against routing table-based router attack in an MPSoC having multiple TEEs. Synthesis results show that proposed countermeasures, viz. Runtime-monitor, Restart-monitor, Intermediate manager, and Auditor, occupy areas that are 26.6, 22, 0.2, and 12.2 % of a routing table-based router area. Apart from these, we propose Ejection address checker and Local monitoring module inside a router that cause 3.4 and 10.6 % increase of a router area, respectively. Simulation results are also given, which shows effectiveness of proposed monitoring-based countermeasures.
Resumo:
In the present study, we have made an effort to develop the novel synthetic antioxidants and antimicrobials with improved potency. The novel benzofuran-gathered C-2,4,6-substituted pyrimidine derivatives 5a, 5b, 5c, 5d, 5e, 5f, 6a, 6b, 6c, 6d, 6e, 6f, 7a, 7b, 7c, 7d, 7e, 7f, 8a, 8b, 8c, 8d, 8e, 8f, 9a, 9b, 9c, 9d, 9e, 9f were synthesized by simple and efficient four-step reaction pathway. Initially, o-alkyl derivative of salicylaldehyde readily furnish corresponding 2-acetyl benzofuran 2 in good yield, upon the treatment with potassium tertiary butoxide in the presence of molecular sieves. Further, Claisen-Schmidt condensation with aromatic aldehydes via treatment with thiourea followed by coupling reaction with different sulfonyl chlorides afforded target compounds. The structures of newly synthesized compounds were confirmed by IR, H-1 NMR, C-13 NMR, mass, and elemental analysis and further screened for their antioxidant and antimicrobial activities. The results showed that the synthesized compounds 8b, 8e, 9b, and 9e produced significant antioxidant activity with 50% inhibitory concentration higher than that of reference, whereas compounds 7d and 7c produced dominant antimicrobial activity at concentrations 1.0 and 0.5mg/mL compared with standard Gentamicin and Nystatin, respectively.
Resumo:
We propose a multiple initialization based spectral peak tracking (MISPT) technique for heart rate monitoring from photoplethysmography (PPG) signal. MISPT is applied on the PPG signal after removing the motion artifact using an adaptive noise cancellation filter. MISPT yields several estimates of the heart rate trajectory from the spectrogram of the denoised PPG signal which are finally combined using a novel measure called trajectory strength. Multiple initializations help in correcting erroneous heart rate trajectories unlike the typical SPT which uses only single initialization. Experiments on the PPG data from 12 subjects recorded during intensive physical exercise show that the MISPT based heart rate monitoring indeed yields a better heart rate estimate compared to the SPT with single initialization. On the 12 datasets MISPT results in an average absolute error of 1.11 BPM which is lower than 1.28 BPM obtained by the state-of-the-art online heart rate monitoring algorithm.
Resumo:
Polyelectrolyte multilayer (PEM) thin film composed of weak polyelectrolytes was designed by layer-by-layer (LbL) assembly of poly(allylamine hydrochloride) (PAH) and poly(methacrylic acid) (PMA) for multi-drug delivery applications. Environmental stimuli such as pH and ionic strength showed significant influence in changing the film morphology from pore-free smooth structure to porous structure and favored triggered release of loaded molecules. The film was successfully loaded with bovine serum albumin (BSA) and ciprofloxacin hydrochloride (CH) by modulating the porous polymeric network of the film. Release studies showed that the amount of release could be easily controlled by changing the environmental conditions such as pH and ionic strength. Sustained release of loaded molecules was observed up to 8 h. The fabricated films were found to be biocompatible with epithelial cells during in-vitro cell culture studies. PEM film reported here not only has the potential to be used as self-responding thin film platform for transdermal drug delivery, but also has the potential for further development in antimicrobial or anti-inflammatory coatings on implants and drug-releasing coatings for stents. (C) 2015 Elsevier B.V. All rights reserved.
Resumo:
Drug repurposing to explore target space has been gaining pace over the past decade with the upsurge in the use of systematic approaches for computational drug discovery. Such a cost and time-saving approach gains immense importance for pathogens of special interest, such as Mycobacterium tuberculosis H37Rv. We report a comprehensive approach to repurpose drugs, based on the exploration of evolutionary relationships inferred from the comparative sequence and structural analyses between targets of FDA-approved drugs and the proteins of M. tuberculosis. This approach has facilitated the identification of several polypharmacological drugs that could potentially target unexploited M. tuberculosis proteins. A total of 130 FDA-approved drugs, originally intended against other diseases, could be repurposed against 78 potential targets in M. tuberculosis. Additionally, we have also made an attempt to augment the chemical space by recognizing compounds structurally similar to FDA-approved drugs. For three of the attractive cases we have investigated the probable binding modes of the drugs in their corresponding M. tuberculosis targets by means of structural modelling. Such prospective targets and small molecules could be prioritized for experimental endeavours, and could significantly influence drug-discovery and drug-development programmes for tuberculosis.
Resumo:
A new electrochemical sensing device was constructed for determination of pesticides. In this report, acetylcholinesterase was bioconjugated onto hybrid nanocomposite, i.e. iron oxide nanoparticles and poly(indole-5-carboxylic acid) (Fe(3)O(4)NPs/Pin5COOH) was deposited electrochemically on glassy carbon electrode. Fe(3)O(4)NPs was showed as an amplified sensing interface at lower voltage which makes the sensor more sensitive and specific. The enzyme inhibition by pesticides was detected within concentrations ranges between 0.1-60 and 1.5-70 nM for malathion and chlorpyrifos, respectively, under optimal experimental conditions (sodium phosphate buffer, pH 7.0 and 25 degrees C). Biosensor determined the pesticides level in water samples (spiked) with satisfactory accuracy (96%-100%). Sensor showed good storage stability and retained 50% of its initial activity within 70 days at 4 degrees C.
Resumo:
Guided waves using piezo-electric wafer active sensors (PWAS) is one of the useful techniques of damage detection. Sensor network optimization with minimal network hardware footprint and maximal area of coverage remains a challenging problem. PWAS sensors are placed at discrete locations in order to inspect damages in plates and the idea has the potential to be extended to assembled structures. Various actuator-sensor configurations are possible within the network in order to identify and locate damages. In this paper we present a correlation based approach to monitor cracks emanating from rivet line using a simulated guided wave signal whose sensor is operating in pulse echo mode. Discussions regarding the identification of phase change due to reflections from the crack are also discussed in this paper.