77 research outputs found
CFD Simulation as an alternate diagnostic tool for a blocked artery
Narrowing or blockage in the coronary arteries supplying blood to the heart muscle manifest as symptoms like chest discomfort or pain and shortness of breath. Symptomatic patients are screened for blocked arteries using coronary angiograms. However, an angiogram provides approximate degree of obstruction. Further, we need to check the significance of obstruction to decide the need for intervention. Interventions like stenting or surgery will depend upon the degree of obstruction and functional impairment.This is evaluated by procedures like measurement of Fractional Flow Reserve (FFR).FFR is the ratio of pressure distal to the stenosis to the pressure proximal to the stenosis.FFR is measured using a specialized probe inserted through a catheter tube, and the technique is expensive.In this study, we propose a workflow to calculate FFR in a non-invasive manner using CFD simulations, and validate it by comparing the results with data from patients
Silver nanoparticles embedded in zeolite membranes: release of silver ions and mechanism of antibacterial action
Amber Nagy1, Alistair Harrison2, Supriya Sabbani3, Robert S Munson, Jr2, Prabir K Dutta3, W James Waldman11Department of Pathology, The Ohio State University; 2Center for Microbial Pathogenesis, Research Institute at Nationwide Children's Hospital, 3Department of Chemistry, The Ohio State University, Columbus, OH, USABackground: The focus of this study is on the antibacterial properties of silver nanoparticles embedded within a zeolite membrane (AgNP-ZM).Methods and Results: These membranes were effective in killing Escherichia coli and were bacteriostatic against methicillin-resistant Staphylococcus aureus. E. coli suspended in Luria Bertani (LB) broth and isolated from physical contact with the membrane were also killed. Elemental analysis indicated slow release of Ag+ from the AgNP-ZM into the LB broth. The E. coli killing efficiency of AgNP-ZM was found to decrease with repeated use, and this was correlated with decreased release of silver ions with each use of the support. Gene expression microarrays revealed upregulation of several antioxidant genes as well as genes coding for metal transport, metal reduction, and ATPase pumps in response to silver ions released from AgNP-ZM. Gene expression of iron transporters was reduced, and increased expression of ferrochelatase was observed. In addition, upregulation of multiple antibiotic resistance genes was demonstrated. The expression levels of multicopper oxidase, glutaredoxin, and thioredoxin decreased with each support use, reflecting the lower amounts of Ag+ released from the membrane. The antibacterial mechanism of AgNP-ZM is proposed to be related to the exhaustion of antioxidant capacity.Conclusion: These results indicate that AgNP-ZM provide a novel matrix for gradual release of Ag+.Keywords: silver nanoparticles, zeolite, antibacterial agent, oxidative stres
Next-Generation Antimalarial Drugs: Hybrid Molecules as a New Strategy in Drug Design
Malaria is a disease that affects nearly 40% of the global population, and chemotherapy remains the mainstay of its control strategy. The global malaria situation is increasingly being exacerbated by the emergence of drug resistance to most of the available antimalarials, necessitating search for novel drugs. A recent rational approach of antimalarial drug design characterized as âcovalent bitherapyâ involves linking two molecules with individual intrinsic activity into a single agent, thus packaging dual-activity into a single hybrid molecule. Current research in this field seems to endorse hybrid molecules as the next-generation antimalarial drugs. If the selective toxicity of hybrid prodrugs can be demonstrated in vivo with good bioavailability at the target site in the parasite, it would offer various advantages including dosage compliance, minimized toxicity, ability to design better drug combinations, and cheaper preclinical evaluation while achieving the ultimate object of delaying or circumventing the development of resistance. This review is focused on several hybrid molecules that have been developed, with particular emphasis on those deemed to have high potential for development for clinical use. Drug Dev Res 71: 20â32, 2010. © 2009 Wiley-Liss, Inc
A tetraoxane-based antimalarial drug candidate that overcomes PfK13-C580Y dependent artemisinin resistance.
K13 gene mutations are a primary marker of artemisinin resistance in Plasmodium falciparum malaria that threatens the long-term clinical utility of artemisinin-based combination therapies, the cornerstone of modern day malaria treatment. Here we describe a multinational drug discovery programme that has delivered a synthetic tetraoxane-based molecule, E209, which meets key requirements of the Medicines for Malaria Venture drug candidate profiles. E209 has potent nanomolar inhibitory activity against multiple strains of P. falciparum and P. vivax in vitro, is efficacious against P. falciparum in in vivo rodent models, produces parasite reduction ratios equivalent to dihydroartemisinin and has pharmacokinetic and pharmacodynamic characteristics compatible with a single-dose cure. In vitro studies with transgenic parasites expressing variant forms of K13 show no cross-resistance with the C580Y mutation, the primary variant observed in Southeast Asia. E209 is a superior next generation endoperoxide with combined pharmacokinetic and pharmacodynamic features that overcome the liabilities of artemisinin derivatives
Silver confined within zeolite EMT nanoparticles: preparation and antibacterial properties
The preparation of pure zeolite nanocrystals (EMT-type framework) and their silver ion-exchanged (Ag+-EMT) and reduced silver (Ag0-EMT) forms is reported. The template-free zeolite nanocrystals are stabilized in water suspensions and used directly for silver ion-exchange and subsequent chemical reduction under microwave irradiation. The high porosity, low Si/Al ratio, high concentration of sodium and ultrasmall crystal size of the EMT-type zeolite permitted the introduction of a high amount of silver using short ion-exchange times in the range of 2â6 h. The killing efficacy of pure EMT, Ag+-EMT and Ag0-EMT against Escherichia coli was studied semi-quantitatively. The antibacterial activity increased with increasing Ag content for both types of samples (Ag+-EMT and Ag0-EMT). The Ag0-EMT samples show slightly enhanced antimicrobial efficacy compared to that of Ag+-EMT, however, the differences are not substantial and the preparation of Ag nanoparticles is not viable considering the complexity of preparation steps
Ostéochimionécrose des maxillaires induite par les bisphosphonates a propos d'un cas clinique et revue de la litterature .
Les bisphosphonates sont des analogues structuraux du pyrophosphate inorganique. Ils possÚdent des propriétés anti-angiogénique, anti-inflammatoire, anti-résorption osseuse et anti-tumorale.
Ils sont communĂ©ment utilisĂ©s dans le traitement de lâostĂ©oporose, ainsi que dans dâautres affections bĂ©nignes (maladie de Paget, rhumatisme inflammatoire, maladie de GaucherâŠ) et dans des affections malignes telles le myĂ©lome et les mĂ©tastases osseuses.
Plusieurs générations de bisphosphonates se sont succédé, améliorant la biodisponibilité du produit actif et son potentiel antirésorption, démontrant ainsi leur efficacité significative en réduisant la morbidité.
Le cas prĂ©sentĂ© est celui dâun patient atteint dâune polyarthrite rhumatoĂŻde traitĂ©e par corticoĂŻdes pendant 10ans et mis sous bisphosphonates pendant 7ans en prĂ©vention des fractures osseuses.
La chute spontanĂ©e de ses implants dentaires a motivĂ© la consultation. Une radiographie panoramique et une tomodensitomĂ©trie maxillo-faciale ont permis de poser le diagnostic dâostĂ©ochimionĂ©crose maxillaire induite par les bisphosphonates.
Lâattitude thĂ©rapeutique Ă©tait sous forme de traitement chirurgical conservateur avec antibiothĂ©rapie et oxygĂ©nothĂ©rapie hyperbare associĂ©e, avec arrĂȘt des bisphosphonates en cause ce qui a permis une bonne cicatrisation muqueuse et osseuse.
Nous avons essayĂ© de dĂ©montrer Ă partir de notre cas que la prise en charge de lâostĂ©ochimionĂ©crose des maxillaires par bisphosphonates est problĂ©matique.
La dĂ©cision dâintervention ou dâabstention est dĂ©licate Ă prendre et lâextension des lĂ©sions peut se faire rapidement
Design of a UV-C pulse generator customised to the photopolymerisation of caffeic acid
Nous proposons une nouvelle mĂ©thode de photopolymĂ©risationradicalaire des composĂ©s phĂ©noliques, qui consiste Ă additionner le radicalhydroxyle (HO·) Ă©lectrophile au cycle benzĂ©nique pour initier la formationde radicaux phĂ©noxyles, qui Ă leur tour rĂ©agissent sur un monomĂšre etengagent lâoligomĂ©risation. HO· est gĂ©nĂ©rĂ© par photolyse de lâeau Ă lâaidedâun rayonnement UV-C 278 nm trĂšs Ă©nergĂ©tique. Ce procĂ©dĂ© a demandĂ© deconcevoir un gĂ©nĂ©rateur dâimpulsions UV-C, pour la premiĂšre fois,modulable en frĂ©quence et en intensitĂ©, et couplĂ© par fibre optique Ă undispositif de focalisation optique pour concentrer les UV-C dans le milieurĂ©actionnel. Il permet de maĂźtriser la production continue de radicaux, enquantitĂ© proportionnelle Ă la durĂ©e dâimpulsion et la puissance optique, Ă une vitesse maintenue infĂ©rieure Ă celle de la photopolymĂ©risation. LegĂ©nĂ©rateur peut dĂ©livrer, pour la premiĂšre fois, une puissance optiquesuffisante (40 mW) pour rĂ©aliser la plupart des rĂ©actions photochimiquesattendues. LâavancĂ©e de la rĂ©action est suivie Ă lâaide dâunphotomultiplicateur silicium (SiPM) posĂ© directement en contact avec lasolution rĂ©actionnelle. Le SiPM est constituĂ© dâune matrice de photodiodesĂ avalanche Ă photon unique (SPAD) fonctionnant en mode Geiger. CephotodĂ©tecteur innovant a permis de mesurer, une fluorescence dâune trĂšsfaible intensitĂ© (10 photons=s) sur une durĂ©e aussi courte que 50 ns, dans ledispositif expĂ©rimental mis au point. Par cette mĂ©thode photochimique, desdimĂšres dâacide cafĂ©ique greffĂ©s de cycle Ă cycle (C-C) sont formĂ©s de façonplus abondante que les autres dimĂšres (C-O-C). Ils prĂ©sentent un fortpotentiel de valorisation dans la mesure oĂč ils sont plus hydrophiles et plussolubles dans lâeau que lâacide cafĂ©ique. Ils conservent les deux fonctionscatĂ©chols et les deux fonctions carboxyliques des monomĂšres, ce qui leurconfĂšre une capacitĂ© antioxydante Ă©levĂ©e. Ils peuvent dâailleurs setransformer en dimĂšres mono ou diquinoniques. Cette expĂ©rimentationinnovante va permettre de diversifier les produits de polymĂ©risation et offrirdes possibilitĂ©s de synthĂšse radicalaire sans lâusage de photosensibilisateursou autres amorceurs chimiques.We designed a novel technique for radical photopolymerisation of phenolic compounds. Our work suggests the addition of the electrophile hydroxyl radical (HO·) to the benzene ring, thus initiating the formation of phenoxyl radicals, which in turn, interacted with a monomer and instigating the oligomerisation. Those hydroxyl radicals HO· are generated via water photolysis through highly energetic 278 nm UV-C irradiation. To achieve this process, we designed a scalable UV-C pulse generator, which offers an easy adjustment of both the frequency and the intensity of the pulses. The generated UV-C pulses are then concentrated towards the reaction medium through an optical focusing system, connected to the generator via an optical fibre. To our knowledge, this generator is the first to offer such a fine-tuning while being accessible to most researchers. This UV-C pulse is able to finely control the production of these radicals, in an amount that is proportional to the pulse duration and to the optical power, in a lower rate than the photopolymerisation one. The generator produces an optical power up to 40 mW, which is high enough to initiate most of the intended photochemical reactions. It is, to our knowledge, the first generator capable of offering this level of UV-C power while being very energy efficient. A Silicon PhotoMultiplier (SiPM), in direct contact with the solution, is used to monitor the reaction progress. The SiPM is made of Single Avalanche PhotoDiodes (SPAD) in Geiger mode. With this photodetector and our custom-made UV-C pulse generator, we were able to measure fluorescence levels as low as 10 photons=s during pulses as short as 50 ns. Using this photochemical technique, caffeic acid dimers, grafted cycle to cycle with a (C-C) bond were generated in a higher abundance than dimers with a (C-O-C) bond. Those C-C bonded dimers are characterised with a high potential value due to being more hydrophilic and more soluble in water than caffeic acid. Plus, they keep the catechol and carboxylic moieties which in turn, grants them a higher antioxidant activity. Besides, they can transform into mono or diquinones dimers. This innovative experiment will allow us to diversify photopolymerisation products and opportunities in radical synthesis without the use of photoinitiators or other chemical initiators
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