199 research outputs found

    Safety Measures for Operating Team and Operation Theater During the Current Scenario of COVID-19

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    The COVID-19 has become a major threat to Pakistan and worldwide, and has become a significant issue for global health, economy and societies. This rapid spread was occurred from Wuhan, China to most of the part of the world. To elaborate the concept and recommendations regarding the safety precautions in operation theater (O.T) and inside associated team during the current scenario of COVID-19. Many research and review articles were studied to collect information about Covid-19 and strategies published in various journals using the search engine, PubMed and Medline. The COVID-19 has significantly changed all aspects of daily life around the world since very start of this year 2020. SARS-CoV-2 (COVID-19), a novel corona virus, has been infected many healthcare workers. In this perspective, hospitals need a strategy to manage their resources, staff and supplies so that patients receive optimal treatment. A decision tree algorithm was developed that defined the recommendations for safety measures in operation theater and operating procedures, these include identifying and developing an isolation room, administrative measures such as transformations in working flow and procedures, introducing personal protective equipment for the employees and formulating anesthetic clinical guidelines. These control actions are essential to enhance the excellence of care provided to COVID-19 patients and to minimize the risk of spread to other patients or staff. The operating room is a dynamic environment with numerous staff like anesthesiologists, physicians, nurses, O.T attendants and technicians; however, we agree that the containment steps are important in order to improve the standard of treatment provided to COVID-19 patients and to minimize the chance of viral spread to patients other than COVID-19 and hospital staff

    Pharmacokinetic interaction potential assessment of cladrin, a potent bioactive constituent of Butea monosperma, and raloxifene, a prescription anti-osteoporotic by in vitro ADME approach

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    Raloxifene is a well-known modulator of estrogen receptors which is structurally similar to tamoxifen. As flavonoids can interact with the estrogen modulator raloxifene in vitro, we performed an in vitro stability study and in situ permeability assay of raloxifene and cladrin in female Sprague-Dawley rats when administered alone and when co-administered. The in vitro study samples were analyzed by HPLC; raloxifene administered individually and in combination with cladrin was compared. In this study, we investigated the absorption, metabolic stability, plasma stability, determination of permeability and plasma protein binding of both drugs in SD rats using an established in situ single pass intestinal perfusion model. Increase in the bioavailability of raloxifene and cladrin alone or in co-administration also could be because of the activation of P-glycoprotein in the rat intestine. Further the present report concludes on the basis of ATPase assay of both raloxifene and cladrin alone and in combination showed that both drugs are P-gp substrate. In in situ permeability assay showed that the both drugs competitively lower the permeability of each other but still the predicted human permeability value lied in the range of high permeability drug.

    Intravenous pharmacokinetics, oral bioavailability, dose proportionality and in situ permeability of anti-malarial lumefantrine in rats

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    <p>Abstract</p> <p>Background</p> <p>Despite the wide spread use of lumefantrine, there is no study reporting the detailed preclinical pharmacokinetics of lumefantrine. For the development of newer anti-malarial combination(s) and selection of better partner drugs, it is long felt need to understand the detailed preclinical pharmacokinetics of lumefantrine in preclinical experimental animal species. The focus of present study is to report bioavailability, pharmacokinetics, dose linearity and permeability of lumefantrine in rats.</p> <p>Methods</p> <p>A single dose of 10, 20 or 40 mg/kg of lumefantrine was given orally to male rats (N = 5 per dose level) to evaluate dose proportionality. In another study, a single intravenous bolus dose of lumefantrine was given to rats (N = 4) at 0.5 mg/kg dose following administration through the lateral tail vein in order to obtain the absolute oral bioavailability and clearance parameters. Blood samples were drawn at predetermined intervals and the concentration of lumefantrine and its metabolite desbutyl-lumefantrine in plasma were determined by partially validated LC-MS/MS method. <it>In-situ </it>permeability study was carried in anaesthetized rats. The concentration of lumefantrine in permeability samples was determined using RP-HPLC.</p> <p>Results</p> <p>For nominal doses increasing in a 1:2:4 proportion, the C<sub>max </sub>and AUC<sub>0-∞ </sub>values increased in the proportions of 1:0.6:1.5 and 1:0.8:1.8, respectively. For lumefantrine nominal doses increasing in a 1:2:4 proportion, the C<sub>max </sub>and the AUC<sub>0-t </sub>values for desbutyl-lumefantrine increased in the proportions of 1:1.45:2.57 and 1:1.08:1.87, respectively. After intravenous administration the clearance (Cl) and volume of distribution (Vd) of lumefantrine in rats were 0.03 (± 0.02) L/h/kg and 2.40 (± 0.67) L/kg, respectively. Absolute oral bioavailability of lumefantrine across the tested doses ranged between 4.97% and 11.98%. Lumefantrine showed high permeability (4.37 × 10<sup>-5 </sup>cm/s) in permeability study.</p> <p>Conclusions</p> <p>The pharmacokinetic parameters of lumefantrine and its metabolite desbutyl-lumefantrine were successfully determined in rats for the first time. Lumefantrine displayed similar pharmacokinetics in the rat as in humans, with multiphasic disposition, low clearance, and a large volume of distribution resulting in a long terminal elimination half-life. The absolute oral bioavailability of lumefantrine was found to be dose dependent. Lumefantrine displayed high permeability in the <it>in-situ </it>permeability study.</p

    Spherical and needle shaped magnetic nanoparticles for friction and magnetic stimulated transformation of microorganisms

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    Supplementary material related to this article can be found online at https://doi.org/10.1016/j.nanoso.2021.100732.Spherical and needle shaped magnetic nanoparticles (MNPs) were synthesized by thermal decomposition, functionalized with 2-pyrrolidinone for the attachment of pUC19 plasmidic DNA and used in transformations assays of Escherichia coli JM109. Frictional and magnetic stimulation were employed for promoting the translocation of the nanoparticle-pUC19 complexes across the cell envelope. Transformants were obtained through frictional stimulation using needle shaped MNPs achieving a maximum transformation efficiency of 3.1 × 102 CFU/g pUC19. Magnetic stimulation was also performed using both types of nanoparticles under conventional magnetofection conditions on a magnetic bioreactor and did not induce transformation of E. coli JM109, possibly due to the field intensity at the region of the cells (100 mT) not being high enough to overcome the rigidity of the bacterial cell envelope. This work substantiates the need for the delivery agent to have a high aspect ratio in order to achieve transformation of prokaryotes. Moreover, it highlights the limitations of magnetic stimulation for translocation of MNPs across the microbial cell wall, as opposed to magnetofection of eukaryotic cells whereby the entry of genetic material can be readily accomplished using spherical MNPs through an endocytotic uptake mechanism.This work was supported by the Portuguese Foundation for Science and Technology (FCT) and the EU fund FEDER (Pro gram COMPETE) under projects PTDC/AMB/68393/2006, PEstOE/EQB/LA0023/2013, UID/FIS/04650/2021, RECI/BBB-EBI/0179/2012 and the Project ‘‘BioEnv - Biotechnology and Bioengineering for a sustainable world’’. The authors also acknowledge FCT for the fellowship SFRH/BD/71661/2010 awarded to Gabriel Mendes under the scope of the MIT-Portugal Program, nanoTherics for providing the Magnefect-Nano IITM device and Paul Brown for help in obtaining ATR-FTIR spectra. Finally, the authors acknowl edge funding by the Spanish State Research Agency (AEI) through the project PID2019-106099RB-C43/AEI/10.13039/501100011033 and from the Basque Government Industry and Education Depart ments under the ELKARTEK and PIBA (PIBA-2018-06) programs, respectively. All authors have given approval to the final version of the manuscript.info:eu-repo/semantics/publishedVersio

    Antifungal activity of amphotericin B conjugated to nanosized magnetite in the treatment of paracoccidioidomycosis

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    This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated (with a double-layer of lauric acid) magnetite nanoparticles. The in vitro tests compared two drugs; i.e., this newly developed form and free amphotericin B. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and with low cytotoxicity to peritoneal macrophages. We also evaluated the efficacy of the nanocomplex in experimental paracoccidioidomycosis. BALB/c mice were intratracheally infected with Paracoccidioides brasiliensis and treated with the compound for 30 or 60 days beginning the day after infection. The newly developed amphotericin B coupled with magnetic nanoparticles was effective against experimental paracoccidioidomycosis, and it did not induce clinical, biochemical or histopathological alterations. The nanocomplex also did not induce genotoxic effects in bone marrow cells. Therefore, it is reasonable to believe that amphotericin B coupled to magnetic nanoparticles and stabilized with bilayer lauric acid is a promising nanotool for the treatment of the experimental paracoccidioidomycosis because it exhibited antifungal activity that was similar to that of free amphotericin B, did not induce adverse effects in therapeutic doses and allowed for a reduction in the number of applications

    Young Investigator: Wahajuddin

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    Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers

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    Wahajuddin,1,2 Sumit Arora21Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 2Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Rae Bareli, IndiaAbstract: A targeted drug delivery system is the need of the hour. Guiding magnetic iron oxide nanoparticles with the help of an external magnetic field to its target is the principle behind the development of superparamagnetic iron oxide nanoparticles (SPIONs) as novel drug delivery vehicles. SPIONs are small synthetic &amp;gamma;-Fe2O3 (maghemite) or Fe3O4 (magnetite) particles with a core ranging between 10 nm and 100 nm in diameter. These magnetic particles are coated with certain biocompatible polymers, such as dextran or polyethylene glycol, which provide chemical handles for the conjugation of therapeutic agents and also improve their blood distribution profile. The current research on SPIONs is opening up wide horizons for their use as diagnostic agents in magnetic resonance imaging as well as for drug delivery vehicles. Delivery of anticancer drugs by coupling with functionalized SPIONs to their targeted site is one of the most pursued areas of research in the development of cancer treatment strategies. SPIONs have also demonstrated their efficiency as nonviral gene vectors that facilitate the introduction of plasmids into the nucleus at rates multifold those of routinely available standard technologies. SPION-induced hyperthermia has also been utilized for localized killing of cancerous cells. Despite their potential biomedical application, alteration in gene expression profiles, disturbance in iron homeostasis, oxidative stress, and altered cellular responses are some SPION-related toxicological aspects which require due consideration. This review provides a comprehensive understanding of SPIONs with regard to their method of preparation, their utility as drug delivery vehicles, and some concerns which need to be resolved before they can be moved from bench top to bedside.Keywords: superparamagnetic iron oxide nanoparticles, SPIONs, targeted delivery, coating, functionalization, targeting ligands, toxicit
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